JP2007016039A - Preventives/remedies for urinary disturbance - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide preventives/remedies which exhibit an excellent effect of improving the urinary function of the bladder (i.e., effects of improving urine flow rate and voiding efficiency) without affecting the urinary pressure or the blood pressure. <P>SOLUTION: The preventives/remedies for voiding disturbance, containing a compound having both of an acetylcholine esterase inhibitory action and an α1 antagonistic action. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a medicine, more specifically to a preventive or therapeutic agent for dysuria.

Lower urinary tract disease is a general term for subjective or objective abnormalities in the process of urinary accumulation (urine accumulation) to excretion (urination), urinary storage disorder (urinary incontinence, frequent urination, etc.), urinary disturbance (urinary difficulty, urination) Pain, urinary tract obstruction, etc.). Lower urinary tract disease is also seen in young people, but in recent years, with the progress of an aging society, the lower urinary tract disease of the elderly, especially dysuria, especially dysuria associated with benign prostatic hyperplasia has become a major social problem. Yes.
Urine urination is controlled by the peripheral nervous system consisting of parasympathetic nerves such as the pelvic nerve, sympathetic nerves such as the hypogastric nerve, and somatic nerves such as the pudendal nerve under the control of the urinary center, and various neurotransmitters (for example, acetylcholine) , Noradrenaline, ATP, substance P, neuropeptide Y, etc.) have been suggested.
As a remedy for dysuria, particularly dysuria, a drug that enhances the contractile force of the bladder muscle (detrusor muscle) or a drug that relaxes the urethral smooth muscle and attenuates urethral resistance is used. For example, cholinergic agents such as besanecol and acetylcholinesterase inhibitors such as distigmine are used as drugs that act on the bladder muscles and increase their contractile force. Impaired urinary storage function of the bladder, and has side effects such as tearing, sweating, gastrointestinal disorders, abdominal pain, etc. No drug has been found.
As an acetylcholinesterase inhibitor having an action of enhancing bladder muscle contraction force, for example, distigmine, neostigmine and the like are known. An acetylcholinesterase inhibitor is an excellent drug considering the physiological mechanism of urination by enhancing the contraction of bladder muscles during urination by enhancing the action of acetylcholine released from pelvic nerve endings during urination. However, distigmine, for example, contracts the bladder muscle, while its strong nicotinic action contracts the urethral sphincter to increase urethral resistance, resulting in poor urination efficiency and inadequate clinical efficacy. Danger is also pointed out. In addition, neostigmine is not used for treatment because of its short duration of action (see, for example, Non-Patent Document 1).
As an agent that relaxes urethral smooth muscle and attenuates urethral resistance, for example, α1 receptor antagonists such as tamsulosin, prazosin, alfuzosin, naphthopidyl, urapidil are used, and subjective symptoms such as residual urine sensation and nocturia Although it has been reported to be effective in improvement, it has a hypotensive effect such as orthostatic hypotension as a side effect, and care is required for treatment.
On the other hand, Patent Document 1 describes an acetylcholinesterase inhibitor used as an agent for preventing or treating dysuria (difficulty in urination). By using a combination of an α1 receptor antagonist and an acetylcholinesterase inhibitor, urine can be obtained. It has been reported that the flow rate can be greatly improved. However, the combined use of the two drugs is not satisfactory in terms of treatment and medical economy, considering the burden on patients to be administered and the time and effort of dispensing. In addition, it has been pointed out that side effects may worsen and fatal accidents may occur due to the drug interaction resulting from the combination, and sufficient care must be taken.

(2) 特許文献３には、中枢神経疾患等の治療剤として用いられるσリガンドとして、例えば下式化合物が記載されている。

(3) 特許文献４には、硫黄含有化合物の合成中間体として、例えば下式化合物が記載されている。

(4) 特許文献５には、精神安定剤等として用いられる4-アミノブチロフェノン類の誘導体として、例えば下式化合物が記載されている。

(5) 特許文献６には、抗菌剤として用いられる化合物として、例えば下式化合物が記載されている。

(6) 特許文献７には、5-HT4受容体リガンドとして、例えば下式化合物が記載されている。

(7) 非特許文献２には、5-HT4受容体拮抗剤として、例えば下式化合物が記載されている。

(8) 特許文献８には、熱産成促進作用、抗肥満作用等を有する化合物として、例えば下式化合物が記載されている。

(9) 特許文献９には、アセチルコリンエステラーゼ阻害剤として、例えば下式化合物が記載されている。

(10) 特許文献１０には、アルツハイマー型痴呆症の治療剤として用いられるアセチルコリンエステラーゼ阻害剤として、例えば下式化合物などが記載されている。

(11) 特許文献１１には、アルツハイマー型痴呆症の治療剤として用いられるアセチルコリンエステラーゼ阻害剤として、例えば下式化合物などが記載されている。

(12) 特許文献１２には、降圧剤または抗不整脈剤として用いられる化合物として、例えば下式化合物などが記載されている。

（13) 特許文献１３には、アルツハイマー型痴呆症の治療剤として用いられるアセチルコリンエステラーゼ阻害剤として、例えば下式化合物などが記載されている。

（14） 特許文献１４には、アルツハイマー型痴呆症の治療剤として用いられるアセチルコリンエステラーゼ阻害剤として、例えば下式化合物などが記載されている。

（15） 特許文献１５には、アルツハイマー型痴呆症の治療剤として用いられるアセチルコリンエステラーゼ阻害剤として、例えば下式化合物などが記載されている。

（16） 特許文献１６には、アルツハイマー型痴呆症の治療剤として用いられるアセチルコリンエステラーゼ阻害剤として、例えば下式化合物などが記載されている。

しかしながら、アセチルコリンエステラーゼ阻害作用とα１受容体拮抗作用を併有する化合物、およびその排尿障害（排尿困難）の予防治療剤としての作用については、今まで何ら報告も示唆も開示もされていない。
また、イン ビボにおける前立腺肥大症に伴う排尿障害治療薬の評価法として、例えば、非特許文献３〜５には、フェニレフリンを負荷した動物を用いて薬物投与による尿道内圧の低下を測定する方法が記載されている。しかしながら、この方法は内圧の変化を観測する手法であって、その時の尿流については測定することができない。
一方、尿道（あるいは膀胱）内圧と尿流を同時に評価する方法としてプレッシャー フロー スタディ(Plessure Flow Study)が知られる。例えば、非特許文献６にはヒトにおけるプレッシャー フロー スタディの適用に関する記載がある。また、非特許文献７〜９には実験動物におけるプレッシャー フロー スタディについて記載されている。しかしながら、これらの文献にはフェニレフリンを負荷した動物モデルを用いたケースがなく、前立腺肥大症に伴う排尿障害治療薬の評価を適切に行うことができない。 In addition, amine compounds having various pharmacological actions have been reported as follows.
(1) Patent Document 2 describes, for example, the following compounds as acetylcholinesterase inhibitors used as therapeutic agents for Alzheimer-type dementia.

(2) Patent Document 3 describes, for example, the following compounds as σ ligands used as therapeutic agents for central nervous system diseases and the like.

(3) Patent Document 4 describes, for example, a compound of the following formula as a synthetic intermediate of a sulfur-containing compound.

(4) Patent Document 5 describes, for example, the following compounds as derivatives of 4-aminobutyrophenones used as tranquilizers and the like.

(5) Patent Document 6 describes, for example, the following compounds as compounds used as antibacterial agents.

(6) Patent Document 7 describes, for example, the following compounds as 5-HT4 receptor ligands.

(7) Non-Patent Document 2 describes, for example, the following compounds as 5-HT4 receptor antagonists.

(8) Patent Document 8 describes, for example, the following compounds as compounds having a heat production promoting action, an anti-obesity action and the like.

(9) Patent Document 9 describes, for example, the following compounds as acetylcholinesterase inhibitors.

(10) Patent Document 10 describes, for example, the following compounds as acetylcholinesterase inhibitors used as therapeutic agents for Alzheimer-type dementia.

(11) Patent Document 11 describes, for example, the following compounds as acetylcholinesterase inhibitors used as therapeutic agents for Alzheimer-type dementia.

(12) Patent Document 12 describes, for example, the following compounds as compounds used as antihypertensive agents or antiarrhythmic agents.

(13) Patent Document 13 describes, for example, the following compounds as acetylcholinesterase inhibitors used as therapeutic agents for Alzheimer-type dementia.

(14) Patent Document 14 describes, for example, the following compounds as acetylcholinesterase inhibitors used as therapeutic agents for Alzheimer-type dementia.

(15) Patent Document 15 describes, for example, the following compounds as acetylcholinesterase inhibitors used as therapeutic agents for Alzheimer-type dementia.

(16) Patent Document 16 describes, for example, the following compounds as acetylcholinesterase inhibitors used as therapeutic agents for Alzheimer-type dementia.

However, there has been no report, suggestion or disclosure of a compound having both an acetylcholinesterase inhibitory action and an α1 receptor antagonistic action, and its action as a preventive and therapeutic agent for dysuria (difficult urination).
Moreover, as a method for evaluating a therapeutic agent for dysuria associated with prostatic hypertrophy in vivo, for example, Non-Patent Documents 3 to 5 include a method for measuring a decrease in urethral pressure due to drug administration using an animal loaded with phenylephrine. Are listed. However, this method is a method for observing a change in internal pressure, and the urine flow at that time cannot be measured.
On the other hand, the pressure flow study (Plessure Flow Study) is known as a method for simultaneously evaluating urethral (or bladder) internal pressure and urine flow. For example, Non-Patent Document 6 describes the application of pressure flow studies in humans. Non-Patent Documents 7 to 9 describe pressure flow studies in experimental animals. However, there is no case using these animal models loaded with phenylephrine in these documents, and it is not possible to appropriately evaluate therapeutic agents for dysuria associated with prostatic hypertrophy.

European Patent Application Publication No. 1118322 European Patent Application No. 562832 International Publication No. 95/131 Pamphlet GB Patent Application No. 1489080 U.S. Pat. No. 4,001312 WO 01/25227 Pamphlet International Publication No. 94/27965 Pamphlet International Publication No. 98/46590 Pamphlet JP-A-6-263733 European Patent Application No. 487071 European Patent Application No. 378207 European Patent Application No. 30044 European Patent Application No. 560235 European Patent Application No. 567090 European Patent Application No. 607864 European Patent Application No. 655451 "Diagnosis and treatment of neurogenic bladder" 2nd edition, Takamichi Hattori, Kosaku Yasuda, Medical School p.105-106, p.139 Bioorganic and Medicinal Chemistry Letter, 1995, Volume 5, p.2119-2122 The Journal of Pharmacology and Experimental Therapeutics, 1999, Vol.291, p.81 The Journal of Pharmacology and Experimental Therapeutics, 2002, 300, p.487 The Journal of Pharmacology and Experimental Therapeutics, 2002, 300, p.495 The mechanics and hydrodynamics of the lower urinary tract, Medical physical handbooks. Bristol, 1980 The Journal of Urology, 1995, vol.154, p.580 American Journal of Physiology, 1995, 269, p.98 Neurourology and Urodynamics, 1996, Volume 15, p.513

  The present invention relates to the development of a preventive / therapeutic agent for dysuria, particularly dysuria, which has a high therapeutic effect and convenience, and has fewer side effects than known compounds known to have a dysuria treatment action and a combination thereof. With the goal. Furthermore, it aims to develop a more effective in vivo evaluation method for the treatment of dysuria associated with benign prostatic hyperplasia.

〔式中の各記号の意義は後述する。〕で表される特異な化学構造のアミン化合物が、その特異な構造に基づいて予想外にもアセチルコリンエステラーゼ阻害作用とα１受容体拮抗作用を併有し、優れた膀胱の排尿機能改善作用(尿流率および排尿効率の改善作用)を示すと共に、排尿圧および血圧には影響を与えず、予想外にも優れた排尿障害、特に排尿困難の予防・治療作用等を有していることを見出した。また、これらの化合物をイン ビボで評価するにあたり、プレッシャー フロー スタディをαアゴニスト（フェニレフリン）負荷モルモットに適用することによって、予想外にも簡便かつ正確に前立腺肥大症に伴う排尿障害治療薬の評価を行えることを見出した。これらに基づいて本発明を完成した。
即ち、本発明は、
〔１〕アセチルコリンエステラーゼ阻害作用とα１拮抗作用を併有する化合物を含有してなる排尿障害予防治療剤、
〔２〕アセチルコリンエステラーゼ阻害作用とα１拮抗作用を併有する、式

〔式中、Ａｒは縮合していてもよい５または６員芳香環基を示し、該芳香環基は置換基を有していてもよく、Ｌは置換基を有していてもよい主鎖の原子数１ないし１０のスペーサーを示すか、またはＡｒとの間で環を形成していてもよく、Ｙは置換基を有していてもよいアミノ基又は置換基を有していてもよい含窒素複素環基を示す。〕で表される化合物又はその塩あるいはそのプロドラッグを含有してなる前記〔１〕記載の剤、
〔３〕Ｌが置換基を有していてもよいＣ_１-１０アルキレン基である前記〔２〕記載の剤、
〔４〕前立腺肥大症に伴う排尿障害の予防治療剤である前記〔１〕記載の剤、
〔５〕化合物のアセチルコリンエステラーゼ阻害作用とα１拮抗作用のそれぞれのＩＣ_５０値が約１：１００〜約１００：１の比率である前記〔１〕記載の剤、
〔６〕化合物のアセチルコリンエステラーゼ阻害作用とα１拮抗作用のそれぞれのＩＣ_５０値が約１：１〜約３０：１の比率である前記〔１〕記載の剤、
〔７〕尿流率の改善作用を示す用量で血圧低下を示さない前記〔１〕記載の剤、
〔８〕投与後の尿流率が投与前に対して約２０％以上改善される用量で、投与後の血圧低下が投与前に対して約１０％以内である前記〔７〕記載の剤、
〔９〕排尿効率の改善作用を示す用量で血圧低下を示さない前記〔１〕記載の剤、
〔１０〕投与後の排尿効率が投与前に対して約１０％以上改善される用量で、投与後の血圧低下が投与前に対して約１０％以内である前記〔９〕記載の剤、
〔１１〕起立性低血圧を伴わない前記〔１〕記載の剤、
〔１２〕哺乳動物に対してアセチルコリンエステラーゼ阻害作用とα１拮抗作用を併有する化合物の有効量を投与することを特徴とする排尿障害の予防・治療方法、
〔１３〕アセチルコリンエステラーゼ阻害作用とα１拮抗作用を併有する化合物の排尿障害予防治療剤製造における使用、
〔１４〕式

〔式中、Ａｒ_１は置換基を有していてもよい二環ないし四環式縮合ベンゼン環基を示し、Ｌ_１は置換基を有していてもよいＣ_４−６アルキレン基を示し、Ｌ_２は置換基を有していてもよいＣ_２−４アルキレン基を示し、Ｒは水素原子又は置換基を有していてもよい炭化水素基を示し、Ｘは結合手、酸素原子又はＮＲ^１ａ（Ｒ^１ａは水素原子、置換基を有していてもよい炭化水素基、アシル基又は置換基を有していてもよい複素環基を示す。）を示し、Ａｒ_２は置換基を有していてもよい芳香環基を示すか、またはＡｒ_２とＲ、もしくはＡｒ_２とＬ_２とが互いに結合し環を形成していてもよい。〕で表される化合物又はその塩、
〔１５〕Ａｒ₁が、式

〔式中、Ａ環は置換基を有していてもよいベンゼン環を示し、Ｂ環は置換基を有していてもよい同素環又は複素環を示し、Ｃ環及びＤ環の一方は置換基を有していてもよい複素環を、他方は置換基を有していてもよい５ないし９員環を示し、Ｅ環、Ｆ環及びＧ環の少なくとも一つの環は置換基を有していてもよい複素環を、その他の環は置換基を有していてもよい５ないし９員環を示す。〕で表される基である前記〔１４〕記載の化合物、
〔１６〕Ａｒ₁が、式

〔式中、Ａ環は前記と同意義を示し、Ｂａ環は置換基を有していてもよい同素環又は複素環を示し、Ｃ”環及びＤ”環はそれぞれ置換基を有していてもよい含窒素複素環を示し、Ｒ^１及びＲ^１'はそれぞれ水素原子、置換基を有していてもよい炭化水素基、アシル基又は置換基を有していてもよい複素環基を示す。〕で表される基である前記〔１４〕記載の化合物、
〔１７〕Ａ環がアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、カルバモイルおよびモノ−又はジ−Ｃ₁₋₆アルキル−カルバモイルから選ばれる１または２個の置換基を有していてもよいベンゼン環で、Ｂａ環、Ｃ”環及びＤ”環がそれぞれＣ₁₋₆アルキル、Ｃ₁₋₆アルキル−カルボニルアミノ及びＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有していてもよく、Ｒ^１及びＲ^１'がそれぞれ（1）水素原子、（2）それぞれヒドロキシおよびＣ₁₋₆アルコキシ−カルボニルから選ばれる１または２個の置換基を有していてもよいＣ₁₋₆アルキル基またはＣ₇₋₁₆アラルキル基または（3）式−(Ｃ＝Ｏ)−Ｒ^２'、 −(Ｃ＝Ｏ)−ＮＲ^２'Ｒ^３'もしくは−ＳＯ_２Ｒ^２'〔式中、Ｒ^２'及びＲ^３'はそれぞれ水素原子、ハロゲン化されていてもよいＣ₁₋₆アルキルまたはＣ₆₋₁₀アリールを示す。〕で表される基である前記〔１６〕記載の化合物、
〔１８〕Ｒが水素原子またはＣ₁₋₄アルキル基である前記〔１４〕記載の化合物、
〔１９〕Ｌ_１がＣ_４-５アルキレン基で、Ｌ_２がフェニル、ヒドロキシまたはオキソを有していてもよいＣ_２-３アルキレン基である前記〔１４〕記載の化合物、
〔２０〕Ａｒ_２がそれぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、Ｃ₆₋₁₀アリール基または窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）である前記〔１４〕記載の化合物、
〔２１〕Ａｒ_２とＲとが互いに結合して形成する環が、式

〔式中、ｐ及びｑはそれぞれ１ないし３の整数を示し、Ｈ環はハロゲン、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキルおよびハロゲン化されていてもよいＣ₁₋₆アルコキシから選ばれる１ないし３個の置換基を有していてもよいベンゼン環を示す。〕で表される環で、Ａｒ_２とＬ_２とが互いに結合して形成する環が、式

〔式中、ｒは０ないし２の整数を、ｓは１ないし３の整数を、かつｒ＋ｓが２ないし５の整数を示し、Ｈ環はハロゲン、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキルおよびハロゲン化されていてもよいＣ₁₋₆アルコキシから選ばれる１ないし３個の置換基を有していてもよいベンゼン環を示す。〕で表される環である前記〔１４〕記載の化合物、
〔２２〕式

〔式中、Ａｒ₃はそれぞれ置換基を有していてもよいベンズイミダゾール環基、キナゾリン環基、1,4-ベンズオキサジン環基または三環ないし四環式縮合ベンゼン環基を示し、Ｌ₃は置換基を有していてもよいＣ_2-4アルキレン基を示し、その他の各記号は前記と同意義を示す。〕で表される化合物又はその塩。
〔２３〕Ａｒ_３が、式

〔式中、Ａ環は前記と同意義を示し、Ｃ'環及びＤ'環はそれぞれオキソ基以外に置換基を有していてもよい含窒素複素環を示す。〕で表される基である前記〔２２〕記載の化合物、
〔２４〕Ｌ_３がエチレン基で、Ｌ_２がフェニル、ヒドロキシまたはオキソを有していてもよいＣ_2-３アルキレン基で、Ｘが結合手または酸素原子である前記〔２２〕記載の化合物、
〔２５〕Ａｒ_２がそれぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、Ｃ₆₋₁₀アリール基または窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）で、Ａｒ_２とＬ_２とが互いに結合して形成する環が、式

〔式中の各記号は前記と同意義を示す。〕で表される環である前記〔２２〕記載の化合物、
〔２６〕式

〔式中、Ａｒ_４はアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、Ｃ₁₋₆アルキル−カルボニルアミノおよびＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有し、さらに１ないし４個の置換基を有していてもよいベンゼン環基を示し、その他の各記号は前記と同意義を示す。〕で表される化合物又はその塩、
〔２７〕Ａｒ_４がアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、Ｃ₁₋₆アルキル−カルボニルアミノおよびＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有し、さらに１または２個のＣ_１−４アルコキシを有していてもよいベンゼン環基で、Ｌ_１がＣ_４−５アルキレン基で、Ｌ_２がヒドロキシまたはオキソを有していてもよいＣ_2-３アルキレン基で、Ｒが水素原子またはＣ₁₋₄アルキル基で、Ｘが結合手で、Ａｒ_２がそれぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、Ｃ₆₋₁₀アリール基または窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）である前記〔２６〕記載の化合物、
〔２８〕式

〔式中、ｎは１または２の整数を示し、Ｌ_４は置換基を有していてもよいＣ_３−５アルキレン基を示し、その他の各記号は前記と同意義を示す。〕で表される化合物又はその塩、
〔２９〕Ｒ^１及びＲ^１'がそれぞれ水素原子またはハロゲン化されていてもよいＣ_１−６アルキル基で、Ｌ_４はＣ_３−４アルキレン基で、Ｌ_２がヒドロキシまたはオキソを有していてもよいＣ_2-３アルキレン基で、Ｒが水素原子またはＣ₁₋₄アルキル基で、Ｘが結合手で、Ａｒ_２がそれぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、Ｃ₆₋₁₀アリール基または窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）である前記〔２８〕記載の化合物、
〔３０〕8-(5-[[2-(2-クロロフェニル)エチル]アミノ]ペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンまたはその塩、
5-[5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]ペンタノイル]-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンまたはその塩、
1,3-ジメチル-5-[5-({2-[2-(トリフルオロメトキシ)フェニル]エチル}
アミノ)ペンタノイル]-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンまたはその塩、
8-{5-[[2-(2-メトキシフェニル)エチル](メチル)アミノ]ペンタノイル}-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンまたはその塩、
8-{5-[[2-(2-メトキシフェニル)エチル](メチル)アミノ]ペンタノイル}-1-メチル-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンまたはその塩、
1,3-ジメチル-5-[5-({2-[2-(トリフルオロメトキシ)フェニル]エチ}アミノ)ペンタノイル]-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンまたはその塩、
8-(5-{[2-(2-クロロフェニル)エチル]アミノ}ペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンまたはその塩、あるいは
5-(5-{[2-(2-クロロフェニル)エチル]アミノ}ペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンまたはその塩、
〔３１〕前記〔１４〕、〔２２〕、〔２６〕もしくは〔２８〕記載の化合物又はその塩のプロドラッグ。
〔３２〕式

〔式中、Ｚ_１は脱離基を、その他の各記号は前記と同意義を示す。〕で表される化合物又はその塩と、式

〔式中、各記号は前記と同意義を示す。〕 で表される化合物又はその塩とを反応させることを特徴とする前記〔１４〕記載の化合物の製造法、
〔３３〕式
Ａｒ_１−Ｈ
〔式中、Ａｒ_１は前記と同意義を示す。〕で表される化合物又はその塩と、式

〔式中、Ｚ_１およびＺ_２はそれぞれ脱離基を、Ｌ_１は前記と同意義を示す。〕で表される化合物又はその塩とを反応させることを特徴とする、式

〔式中、各記号は前記と同意義を示す。〕で表される化合物又はその塩の製造法、
〔３４〕触媒として塩化亜鉛を、溶媒としてニトロアルカンを用いる前記〔３３〕記載の製造法、
〔３５〕前記〔１４〕、〔２２〕、〔２６〕もしくは〔２８〕記載の化合物又はその塩あるいはそのプロドラッグからなる医薬、
〔３６〕排尿障害予防治療剤である前記〔３５〕記載の医薬、
〔３７〕前立腺肥大症に伴う排尿障害の予防治療剤である前記〔３５〕記載の医薬、
〔３８〕低緊張膀胱による排尿障害の予防治療剤である前記〔３７〕記載の医薬、
〔３９〕哺乳動物に対して前記〔１４〕、〔２２〕、〔２６〕もしくは〔２８〕記載の化合物又はその塩あるいはそのプロドラッグの有効量を投与することを特徴とする排尿障害の予防・治療方法、
〔４０〕前記〔１４〕、〔２２〕、〔２６〕もしくは〔２８〕記載の化合物又はその塩あるいはそのプロドラッグの排尿障害予防治療剤製造における使用、
〔４１〕αアゴニストを負荷した動物モデルを用いることを特徴とするプレッシャー フロー スタディによる排尿障害予防治療作用を有する化合物又はその塩のスクリーニング方法、
〔４２〕αアゴニストがフェニレフリンである前記〔４１〕記載のスクリーニング方法、
〔４３〕前記〔４１〕記載のスクリーニング方法で得られる排尿障害予防治療作用を有する化合物またはその塩などに関する。 In view of such a current situation, the present inventors proceeded with exploratory research on a new urination disorder preventive and therapeutic agent with high urination efficiency, particularly a preventive and therapeutic agent for dysuria,

[The significance of each symbol in the formula will be described later. An amine compound having a specific chemical structure represented by the above formula unexpectedly has both an acetylcholinesterase inhibitory action and an α1 receptor antagonistic action based on the specific structure, and has an excellent action to improve bladder urination function (urine The flow rate and urination efficiency were improved), and the urination pressure and blood pressure were not affected. It was. In addition, when evaluating these compounds in vivo, a pressure flow study was applied to alpha agonist (phenylephrine) -loaded guinea pigs to unexpectedly easily and accurately evaluate drugs for treating urination disorders associated with benign prostatic hyperplasia. I found out what I can do. Based on these, the present invention was completed.
That is, the present invention
[1] A preventive or therapeutic agent for dysuria, comprising a compound having both an acetylcholinesterase inhibitory action and an α1 antagonistic action,
[2] Formula having both acetylcholinesterase inhibitory action and α1 antagonistic action

[In the formula, Ar represents an optionally condensed 5- or 6-membered aromatic ring group, the aromatic ring group may have a substituent, and L may have a substituent. Or a ring formed with Ar, and Y may have an amino group or a substituent which may have a substituent. A nitrogen-containing heterocyclic group is shown. Or a salt thereof or a prodrug thereof, the agent according to the above [1],
[3] The agent according to the above [2], wherein L is a C _1-10 alkylene group which may have a substituent.
[4] The agent of the above-mentioned [1], which is a preventive and therapeutic agent for dysuria associated with benign prostatic hyperplasia,
[5] The agent according to the above [1], wherein the IC ₅₀ values of the acetylcholinesterase inhibitory action and α1 antagonistic action of the compound are each in a ratio of about 1: 100 to about 100: 1.
[6] The agent according to the above [1], wherein each compound has an IC ₅₀ value of about 1: 1 to about 30: 1 for the acetylcholinesterase inhibitory action and the α1 antagonistic action of the compound,
[7] The agent according to the above [1], which does not show a decrease in blood pressure at a dose exhibiting an effect of improving urinary flow rate,
[8] The agent according to [7] above, wherein the urinary flow rate after administration is improved by about 20% or more compared to before administration, and the blood pressure decrease after administration is within about 10% compared to before administration,
[9] The agent according to the above [1], which does not show a decrease in blood pressure at a dose exhibiting an effect of improving urination efficiency,
[10] The agent according to [9] above, wherein the urination efficiency after administration is improved by about 10% or more compared to before administration, and the blood pressure decrease after administration is within about 10% compared to before administration,
[11] The agent according to the above [1], which is not accompanied by orthostatic hypotension,
[12] A method for preventing / treating dysuria, comprising administering an effective amount of a compound having both an acetylcholinesterase inhibitory action and an α1 antagonistic action to a mammal,
[13] Use of a compound having both an acetylcholinesterase inhibitory action and an α1 antagonistic action in the manufacture of a dysuria preventive or therapeutic agent,
[14] Formula

[In the formula, Ar ₁ represents a bicyclic to tetracyclic fused benzene ring group which may have a substituent, L ₁ represents a C _4-6 alkylene group which may have a substituent, L ₂ represents a C _2-4 alkylene group which may have a substituent, R represents a hydrogen atom or a hydrocarbon group which may have a substituent, X represents a bond, an oxygen atom or NR ^1a (R ^1a represents a hydrogen atom, a hydrocarbon group which may have a substituent, an acyl group or a heterocyclic group which may have a substituent), and Ar ₂ has a substituent. An aromatic ring group that may be present, or Ar ₂ and R, or Ar ₂ and L ₂ may be bonded to each other to form a ring. Or a salt thereof,
[15] Ar ₁ represents the formula

[In formula, A ring shows the benzene ring which may have a substituent, B ring shows the homologous ring or heterocyclic ring which may have a substituent, and one of C ring and D ring is A heterocyclic ring which may have a substituent, the other represents a 5- to 9-membered ring which may have a substituent, and at least one of the E ring, the F ring and the G ring has a substituent. And the other ring represents a 5- to 9-membered ring which may have a substituent. A compound represented by the above [14],
[16] Ar ₁ represents the formula

[Wherein, A ring represents the same meaning as described above, Ba ring represents an allocyclic or heterocyclic ring which may have a substituent, and C ″ ring and D ″ ring each have a substituent. Each of R ¹ and R ^{1 ′} represents a hydrogen atom, a hydrocarbon group optionally having substituent (s), an acyl group or a heterocyclic group optionally having substituent (s). Show. A compound represented by the above [14],
[17] The ring A has 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. 1 or 2 substituted benzene rings, wherein the Ba ring, C ″ ring and D ″ ring are each selected from C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino And R ¹ and R ^{1 ′} each have 1 or 2 substituents selected from (1) a hydrogen atom, and (2) each hydroxy and C _1-6 alkoxy-carbonyl. C _1-6 alkyl group or C _7-16 aralkyl group or (3) Formula — (C═O) —R ^{2 ′} , — (C═O) —NR ^{2 ′} R ^{3 ′} or —SO ₂ R ^{2 'wherein,} R ^2' and R ^{3 'which} Re represents a hydrogen atom, an optionally halogenated and C _1-6 alkyl or C _6-10 aryl. A compound represented by the above [16],
[18] The compound according to the above [14], wherein R is a hydrogen atom or a C _1-4 alkyl group,
[19] The compound according to the above [14], wherein L ₁ is a C _4-5 alkylene group and L ₂ is a C _2-3 alkylene group optionally having phenyl, hydroxy or oxo,
[20] 1 to 3 substitutions wherein Ar ₂ is each selected from halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, optionally halogenated C _1-6 alkoxy and aminosulfonyl A C _6-10 aryl group which may have a group, or a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom (a benzene ring is condensed) The compound of the above-mentioned [14], which may be
[21] A ring formed by combining Ar ₂ and R with each other has the formula

[Wherein, p and q each represent an integer of 1 to 3, and the H ring is selected from halogen, hydroxy, optionally halogenated C _1-6 alkyl and optionally halogenated C _1-6 alkoxy. A benzene ring optionally having 1 to 3 substituents is shown. A ring formed by combining Ar ₂ and L ₂ with each other is represented by the formula:

[Wherein, r represents an integer of 0 to 2, s represents an integer of 1 to 3, and r + s represents an integer of 2 to 5, and the H ring is halogen, hydroxy, C ₁₋ which may be halogenated. ₆ represents a benzene ring optionally having 1 to 3 substituents selected from alkyl and optionally halogenated C _1-6 alkoxy. A compound represented by the above [14], which is a ring represented by:
[22] Formula

Wherein, Ar ₃ good benzimidazole ring group which may have a substituent, respectively, a quinazoline ring group, a 1,4-benzoxazine ring group or a tricyclic or tetracyclic condensed benzene ring group, L _{3 Represents a} C _2-4 alkylene group which may have a substituent, and other symbols are as defined above. Or a salt thereof.
[23] Ar ₃ is a formula

[Wherein, A ring represents the same meaning as described above, and C ′ ring and D ′ ring each represent a nitrogen-containing heterocyclic ring which may have a substituent other than an oxo group. A compound represented by the above [22],
[24] The compound according to [22] above, wherein L ₃ is an ethylene group, L ₂ is a C _2-3 alkylene group optionally having phenyl, hydroxy or oxo, and X is a bond or an oxygen atom,
[25] 1 to 3 substitutions wherein Ar ₂ is each selected from halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, optionally halogenated C _1-6 alkoxy and aminosulfonyl A C _6-10 aryl group which may have a group, or a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom (a benzene ring is condensed) And a ring formed by combining Ar ₂ and L ₂ with each other has the formula

[Each symbol in the formula is as defined above. A compound represented by the above [22],
[26] Formula

[Wherein Ar ₄ represents one or two substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. And a benzene ring group which may further have 1 to 4 substituents, and other symbols are as defined above. Or a salt thereof,
[27] Ar ₄ has 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino And a benzene ring group which may have 1 or 2 C _1-4 alkoxy, L ₁ is a C _4-5 alkylene group, and L ₂ may have hydroxy or oxo. _{A 2-3} alkylene group, R is a hydrogen atom or a C _1-4 alkyl group, X is a bond, and Ar ₂ is halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, halogen A C _6-10 aryl group or nitrogen atom, oxygen atom and sulfur which may have 1 to 3 substituents selected from optionally substituted C _1-6 alkoxy and aminosulfonyl The compound of the above-mentioned [26], which is a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from atoms (a benzene ring may be condensed),
[28] Formula

[Wherein, n represents an integer of 1 or 2, L ₄ represents an optionally substituted C _3-5 alkylene group, and other symbols are as defined above]. Or a salt thereof,
[29] R ¹ and R ^{1 ′} are each a hydrogen atom or an optionally halogenated C _1-6 alkyl group, L ₄ is a C _3-4 alkylene group, and L ₂ has hydroxy or oxo. An optionally substituted C _2-3 alkylene group, R is a hydrogen atom or a C _1-4 alkyl group, X is a bond, and Ar ₂ is a halogenated, nitro, hydroxy, or optionally halogenated C _1- C _6-10 aryl group or nitrogen atom, oxygen atom and sulfur optionally having 1 to 3 substituents selected from ₆ alkyl, optionally halogenated C _1-6 alkoxy and aminosulfonyl The compound according to the above [28], which is a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from atoms (the benzene ring may be condensed);
[30] 8- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one Or its salt,
5- [5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
1,3-dimethyl-5- [5-({2- [2- (trifluoromethoxy) phenyl] ethyl}
Amino) pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
8- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H)- On or its salt,
8- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H) -one or a salt thereof,
1,3-dimethyl-5- [5-({2- [2- (trifluoromethoxy) phenyl] ethy} amino) pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one or a salt thereof Or
5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
[31] A prodrug of the compound according to [14], [22], [26] or [28] or a salt thereof.
[32] Formula

[In the formula, Z ₁ represents a leaving group, and other symbols are as defined above. A compound represented by the formula:

[Wherein each symbol is as defined above. A process for producing the compound of the above-mentioned [14], which comprises reacting the compound represented by the formula:
[33] formula _Ar 1 -H
[Wherein Ar ₁ is as defined above. A compound represented by the formula:

[Wherein, Z ₁ and Z ₂ each represent a leaving group, and L ₁ represents the same meaning as described above. A compound represented by the formula:

[Wherein each symbol is as defined above. A method for producing a compound represented by the formula:
[34] The production method of the above-mentioned [33], wherein zinc chloride is used as a catalyst and nitroalkane is used as a solvent.
[35] A pharmaceutical comprising the compound of the above-mentioned [14], [22], [26] or [28], a salt thereof or a prodrug thereof,
[36] The medicament according to the above [35], which is an agent for preventing or treating urination disorder,
[37] The pharmaceutical according to the above [35], which is a preventive and therapeutic agent for dysuria associated with benign prostatic hyperplasia,
[38] The medicament according to [37] above, which is a prophylactic / therapeutic agent for dysuria due to low tension bladder
[39] Prevention of micturition disorder, comprising administering an effective amount of the compound of the above-mentioned [14], [22], [26] or [28] or a salt thereof or a prodrug thereof to a mammal Method of treatment,
[40] Use of the compound according to [14], [22], [26] or [28] or a salt thereof or a prodrug thereof in the manufacture of a preventive or therapeutic agent for urination disorder,
[41] A screening method for a compound having a urination disorder preventive and therapeutic action by pressure flow study or a salt thereof, characterized by using an animal model loaded with an α agonist.
[42] The screening method according to [41] above, wherein the α agonist is phenylephrine,
[43] The present invention relates to a compound having a urinary dysfunction preventive or therapeutic effect obtained by the screening method of [41] or a salt thereof.

Among dysuria, for example, dysuria associated with prostatic hypertrophy is considered to be caused by urethral compression by an enlarged prostate and functional contraction of the prostate and urethra due to enhancement of the sympathetic nervous system. In the treatment, administration of an acetylcholinesterase inhibitor alone, that is, enhancing the contractile force of the bladder muscle (detrusor muscle) in the blocked state of the urethra has a risk of causing high-pressure urination. α ₁ receptor antagonist is a drug that improves the functional contraction of the prostate and urethra, and there is no danger of high-pressure urination, but it basically has antihypertensive effects and has side effects such as orthostatic hypotension . On the other hand, the "compound having both acetylcholinesterase inhibitory action and α1 antagonistic action" used in dysuria prophylactic treatment agent of the present invention (hereinafter, sometimes abbreviated as Compound A), based on the alpha ₁ antagonism, urethra It relaxes smooth muscles and attenuates urethral resistance, and at the same time enhances contractile force of bladder muscles (detrusor muscles) based on acetylcholinesterase inhibitory action. Therefore, the preventive or therapeutic agent for dysuria comprising the compound A of the present invention has a lower risk of high-pressure urination than the single administration of an acetylcholinesterase inhibitor. In addition, the urinary flow rate and the efficiency of micturition are improved at a lower dose as compared with the single administration of the α ₁ receptor antagonist, and thus the influence on blood pressure is less.
Next, the superiority of Compound A used in the present invention over “combination treatment” of an α ₁ receptor antagonist and an acetylcholinesterase inhibitor will be described. In general, the pharmacokinetics of a drug varies from drug to drug, so in order to obtain the optimal effect in “combination therapy”, detailed settings such as the number of administrations and timing of administration are required, which imposes a burden on the patient and doctor to be administered At the same time, time and effort for dispensing etc. increases. In recent years, it has been found that side effects may be enhanced when a drug interaction occurs in combination with a drug, and death may occur in some cases. Therefore, in “combination therapy”, it is necessary to pay sufficient attention to drug interactions. On the other hand, since compound A used in the present invention can be treated with a single agent, it is possible to reduce the burden on patients and doctors to be administered and troublesome preparation, and there is no worry of drug interaction. Compared with "combination treatment", it is more preferable in terms of treatment and medical economy.
Regarding the acetylcholinesterase inhibitory action of compound A used in the present invention, for example, in the in vitro enzyme inhibition test 1a) described below, the IC ₅₀ value is preferably about 1 μM or less, more preferably about 0.5 μM or less. preferable.
In addition, α ₁ receptors are classified into three subtypes, α _1A , α _1B and α _1D (Pharmacological Reviews, 1995, 47, 267). In human prostate, about 70% of α 1 receptors are α It is known that it is a _1A subtype and that human prostate smooth muscle contraction is controlled by the _α1A subtype (Journalof Urology, 1993, 150, 546; Molecular Pharmacology, 1994, 45, 703). Regarding the α ₁ antagonism of Compound A, for example, in the in vitro test 1b) described below, the IC ₅₀ value of α _1A receptor binding inhibitory activity is preferably about 1 μM or less, and about 0.5 μM or less. More preferred.

Regarding the balance of both actions in Compound A, the IC ₅₀ values of the acetylcholinesterase inhibitory action and α ₁ (α _1A ) antagonistic action in in vitro tests are preferably about 1: 1000 to about A ratio of 1000: 1, more preferably about 1: 100 to about 100: 1, and even more preferably about 1:20 to about 20: 1 is included. Among both effects, compounds having stronger α1 antagonism are preferable, for example, those in which the IC ₅₀ values of acetylcholinesterase inhibition and α ₁ antagonism are in a ratio of about 1: 1 to about 30: 1. It is done. In addition, the balance of both actions can be more accurately evaluated by an in vivo test. Specifically, in Test 2 described below, the urine pressure is not affected (the urine pressure is not increased), and the urinary flow rate and urination efficiency are improved (the urine flow rate after administration is before administration) In contrast, the urination efficiency after administration is improved by about 10% or more compared to before administration), and the dose that shows an improvement effect does not affect blood pressure (lowering blood pressure after administration) Is preferably within about 10% of that before administration).
Compound A used in the present invention may be a compound having any molecular structure as long as it is a single compound that has both an acetylcholinesterase inhibitory action and an α1 antagonistic action. Among these, an amine compound in which a hydrogen atom of ammonia is substituted with a hydrocarbon group is preferable, and a primary amine compound, a secondary amine compound, and a tertiary amine compound are more preferable.
Compound A used in the present invention has an inhibitory action on acetylcholinesterase by becoming a salt, such as a salt or prodrug of compound (I), (Ia), (Ib), (Ic) or (Id) described later. And a compound that converts to a compound having both an α1 antagonistic action and a compound that converts to a compound having both an acetylcholinesterase inhibitory action and an α1 antagonistic action by a reaction with an enzyme, gastric acid or the like under physiological conditions in vivo.

〔式中、Ａｒは縮合していてもよい５または６員芳香環基を示し、該芳香環基は置換基を有していてもよく、Ｌは置換基を有していてもよい主鎖の原子数１ないし１０のスペーサーを示すか、またはＡｒとの間で環を形成していてもよく、Ｙは置換基を有していてもよいアミノ基又は置換基を有していてもよい含窒素複素環を示す。〕で表される化合物（以下、化合物（Ｉ）と略記することもある）又はその塩。
上記式中、Ａｒで示される「縮合していてもよい５または６員芳香環基を示し、該芳香環基は置換基を有していてもよく」の「置換基」としては、例えば、（i）ハロゲン化されていてもよい低級アルキル基、（ii）ハロゲン原子（例えば、フルオロ、クロル、ブロム、ヨード等）、（iii）低級アルキレンジオキシ基（例えば、メチレンジオキシ、エチレンジオキシ等のＣ_1-3アルキレンジオキシ基等）、（iv）ニトロ基、（v）シアノ基、（vi）ヒドロキシ基、（vii）ハロゲン化されていてもよい低級アルコキシ基、（viii）シクロアルキル基（例えば、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル等のＣ_3-6シクロアルキル基等）、（ix）ハロゲン化されていてもよい低級アルキルチオ基、（x）アミノ基、（xi）モノ−低級アルキルアミノ基（例えば、メチルアミノ、エチルアミノ、プロピルアミノ等のモノ−Ｃ_1-6アルキルアミノ基等）、（xii）ジ−低級アルキルアミノ基（例えば、ジメチルアミノ、ジエチルアミノ等のジ−Ｃ_1-6アルキルアミノ基等）、（xiii）５ないし７員環状アミノ基（例えば、１個の窒素原子以外に窒素原子、酸素原子及び硫黄原子等から選ばれるヘテロ原子を１ないし３個有していてもよい５ないし７員環状アミノ基（例、1-ピロリジニル、ピペリジノ、1-ピペラジニル、モルホリノ、チオモルホリノ等）等）、（xiv）低級アルキル−カルボニルアミノ基（例えば、アセチルアミノ、プロピオニルアミノ、ブチリルアミノ等のＣ_1-6アルキル−カルボニルアミノ基等）、（xv）低級アルキルスルホニルアミノ基（例えば、メチルスルホニルアミノ、エチルスルホニルアミノ、プロピルスルホニルアミノ等のＣ_1-6アルキルスルホニルアミノ基等）、（xvi）低級アルコキシ−カルボニル基（例えば、メトキシカルボニル、エトキシカルボニル、プロポキシカルボニル、イソブトキシカルボニル等のＣ_1-6アルコキシ−カルボニル基等）、（xvii）カルボキシ基、（xviii）低級アルキル−カルボニル基（例えば、メチルカルボニル、エチルカルボニル、ブチルカルボニル等のＣ_1-6アルキル−カルボニル基等）、（xix）シクロアルキル−カルボニル基（例えば、シクロプロピルカルボニル、シクロブチルカルボニル、シクロペンチルカルボニル、シクロヘキシルカルボニル等のＣ_3-6シクロアルキル−カルボニル基等）、（xx）カルバモイル基、チオカルバモイル基、（xxi）モノ−低級アルキル−カルバモイル基（例えば、メチルカルバモイル、エチルカルバモイル、プロピルカルバモイル、ブチルカルバモイル等のモノ−Ｃ_1-6アルキル−カルバモイル基等）、（xxii）ジ−低級アルキル−カルバモイル基（例えば、ジエチルカルバモイル、ジブチルカルバモイル等のジ−Ｃ_1-6アルキル−カルバモイル基等）、（xxiii）低級アルキルスルホニル基（例えば、メチルスルホニル、エチルスルホニル、プロピルスルホニル等のＣ_1-6アルキルスルホニル基等）、（xxiv）シクロアルキルスルホニル基（例えば、シクロペンチルスルホニル、シクロヘキシルスルホニル等のＣ_3-6シクロアルキルスルホニル等）、（xxv）フェニル基、（xxvi）ナフチル基、（xxvii）モノ−フェニル−低級アルキル基（例えばベンジル、フェニルエチル等のモノ−フェニル−Ｃ_1-6アルキル基等）、（xxviii）ジ−フェニル−低級アルキル基（例えば、ジフェニルメチル、ジフェニルエチル等のジ−フェニル−Ｃ_1-6アルキル基等）、（xxix）モノ−フェニル−低級アルキル−カルボニルオキシ基（例えばフェニルメチルカルボニルオキシ、フェニルエチルカルボニルオキシ等のモノ−フェニル−Ｃ_1-6アルキル−カルボニルオキシ基等）、（xxx）ジ−フェニル−低級アルキル−カルボニルオキシ基（例えば、ジフェニルメチルカルボニルオキシ、ジフェニルエチルカルボニルオキシ等のジ−フェニル−Ｃ_1-6アルキル−カルボニルオキシ基等）、（xxxi）フェノキシ基、（xxxii）モノ−フェニル−低級アルキル−カルボニル基（例えばフェニルメチルカルボニル、フェニルエチルカルボニル等のモノ−フェニル−Ｃ_1-6アルキル−カルボニル基等）、（xxxiii）ジ−フェニル−低級アルキル−カルボニル基（例えば、ジフェニルメチルカルボニル、ジフェニルエチルカルボニル等のジ−フェニル−Ｃ_1-6アルキル−カルボニル基等）、（xxxiv）ベンゾイル基、（xxxv）フェノキシカルボニル基、（xxxvi）フェニル−低級アルキル−カルバモイル基（例えば、フェニル−メチルカルバモイル、フェニル−エチルカルバモイル等のフェニル−Ｃ_1-6アルキル−カルバモイル基等）、（xxxvii）フェニルカルバモイル基、（xxxviii）フェニル−低級アルキル−カルボニルアミノ基（例えば、フェニル−メチルカルボニルアミノ、フェニル−エチルカルボニルアミノ等のフェニル−Ｃ_1-6アルキル−カルボニルアミノ基等）、（xxxix）フェニル−低級アルキルアミノ基（例えば、フェニル−メチルアミノ、フェニル−エチルアミノ等のフェニル−Ｃ_1-6アルキルアミノ基等）、（xxxx）フェニル−低級アルキルスルホニル基（例えば、フェニル−メチルスルホニル、フェニル−エチルスルホニル等のフェニル−Ｃ_1-6アルキルスルホニル基等）、（xxxxi）フェニルスルホニル基、（xxxxii）フェニル−低級アルキルスルフィニル基（例えば、フェニル−メチルスルフィニル、フェニル−エチルスルフィニル等のフェニル−Ｃ_1-6アルキルスルフィニル基等）、（xxxxiii）フェニル−低級アルキルスルホニルアミノ基（例えば、フェニル−メチルスルホニルアミノ、フェニル−エチルスルホニルアミノ等のフェニル−Ｃ_1-6アルキルスルホニルアミノ基等）、（xxxxiv）フェニルスルホニルアミノ基、（xxxxv）５ないし７員環状アミノ−カルボニル基（例えば、１個の窒素原子以外に窒素原子、酸素原子及び硫黄原子等から選ばれるヘテロ原子を１ないし３個有していてもよい５ないし７員環状アミノ−カルボニル基(例、(1-ピロリジニル)カルボニル、ピペリジノカルボニル、(1-ピペラジニル)カルボニル、モルホリノカルボニル、チオモルホリノカルボニル基等)等）、（xxxxvi）アミノスルホニル基、（xxxxvii）モノ−低級アルキルアミノスルホニル基（例えば、メチルアミノスルホニル、エチルアミノスルホニル、プロピルアミノスルホニル、ブチルアミノスルホニル等のモノ−Ｃ_1-6アルキルアミノスルホニル基等）、（xxxxviii）ジ−低級アルキルアミノスルホニル基（例えば、ジエチルアミノスルホニル、ジブチルアミノスルホニル等のジ−Ｃ_1-6アルキルアミノスルホニル基等）、（xxxxix）５ないし７員環状アミノ−スルホニル基（例えば、１個の窒素原子以外に窒素原子、酸素原子及び硫黄原子等から選ばれるヘテロ原子を１ないし３個有していてもよい５ないし７員環状アミノ−スルホニル基(例、(1-ピロリジニル)スルホニル、ピペリジノスルホニル、(1-ピペラジニル) スルホニル、モルホリノスルホニル、チオモルホリノスルホニル基等)等）、（xxxxx）アミノカルボニルオキシ基、（xxxxxi）モノ−低級アルキルアミノカルボニルオキシ基（例えば、メチルアミノカルボニルオキシ、エチルアミノカルボニルオキシ、プロピルアミノカルボニルオキシ等のモノ−Ｃ_1-6アルキルアミノカルボニルオキシ基等）、（xxxxxii）ジ−低級アルキルアミノカルボニルオキシ基（例えば、ジメチルアミノカルボニルオキシ、ジエチルアミノカルボニルオキシ等のジ−Ｃ_1-6アルキルアミノカルボニルオキシ基等）及び（xxxxxiii）５ないし７員環状アミノ−カルボニルオキシ基（例えば、１個の窒素原子以外に窒素原子、酸素原子及び硫黄原子等から選ばれるヘテロ原子を１ないし３個有していてもよい５ないし７員環状アミノ−カルボニルオキシ基(例、(1-ピロリジニル)カルボニルオキシ、ピペリジノカルボニルオキシ、(1-ピペラジニル) カルボニルオキシ、モルホリノカルボニルオキシ、チオモルホリノカルボニルオキシ基等)等）（前記（xxv）ないし（xxxxiv）のフェニル基、ナフチル基、モノ−フェニル−低級アルキル基、ジ−フェニル−低級アルキル基、モノ−フェニル−低級アルキル−カルボニルオキシ基、ジ−フェニル−低級アルキル−カルボニルオキシ基、フェノキシ基、モノ−フェニル−低級アルキル−カルボニル基、ジ−フェニル−低級アルキル−カルボニル基、ベンゾイル基、フェノキシカルボニル基、フェニル−低級アルキル−カルバモイル基、フェニルカルバモイル基、フェニル−低級アルキル−カルボニルアミノ基、フェニル−低級アルキルアミノ基、フェニル−低級アルキルスルホニル基、フェニルスルホニル基、フェニル−低級アルキルスルフィニル基、フェニル−低級アルキルスルホニルアミノ基及びフェニルスルホニルアミノ基におけるフェニル基の部分は、更に、例えば、低級アルキル基（例えば、メチル、エチル、プロピル、イソプロピル、ブチル、sec-ブチル、tert-ブチル、ペンチル、ヘキシル等のＣ_1-6アルキル等）、低級アルコキシ基（例えば、メトキシ、エトキシ、プロポキシ、イソプロポキシ、ブトキシ、イソブトキシ、sec-ブトキシ、tert-ブトキシ等のＣ_1-6アルコキシ等）、ハロゲン原子（例えば、クロル、ブロム、ヨード等）、ヒドロキシ基、ベンジルオキシ基、アミノ基、モノ−低級アルキルアミノ基（例えば、メチルアミノ、エチルアミノ、プロピルアミノ等のモノ−Ｃ_1-6アルキルアミノ等）、ジ−低級アルキルアミノ基（例えば、ジメチルアミノ、ジエチルアミノ等のジ−Ｃ_1-6アルキルアミノ等）、ニトロ基、低級アルキル−カルボニル基（例えば、メチルカルボニル、エチルカルボニル、ブチルカルボニル等のＣ_1-6アルキル−カルボニル等）、ベンゾイル基等から選ばれた１ないし４個の置換基を有していてもよい。）等が挙げられる。Ａｒで示される「縮合していてもよい５または６員芳香環基」はこれら（i）〜（xxxxxiii）の置換基を１ないし４個、好ましくは１または２個有していてもよい。 Specifically, the compounds described below are preferable.
formula

[In the formula, Ar represents an optionally condensed 5- or 6-membered aromatic ring group, the aromatic ring group may have a substituent, and L may have a substituent. Or a ring formed with Ar, and Y may have an amino group or a substituent which may have a substituent. A nitrogen-containing heterocyclic ring is shown. Or a salt thereof (hereinafter sometimes abbreviated as compound (I)).
In the above formula, as the “substituent” of “showing an optionally condensed 5- or 6-membered aromatic ring group, which may have a substituent” represented by Ar, for example, (I) an optionally halogenated lower alkyl group, (ii) a halogen atom (eg, fluoro, chloro, bromo, iodo, etc.), (iii) a lower alkylenedioxy group (eg, methylenedioxy, ethylenedioxy) C _1-3 alkylenedioxy group such as), (iv) nitro group, (v) cyano group, (vi) hydroxy group, (vii) optionally halogenated lower alkoxy group, (viii) cycloalkyl Groups (eg, C _3-6 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), (ix) optionally halogenated lower alkylthio groups, (x) amino groups, (xi) mono-lower A Alkylamino groups (eg, mono-C _1-6 alkylamino groups such as methylamino, ethylamino, propylamino, etc.), (xii) di-lower alkylamino groups (eg, di-C _1-, such as dimethylamino, diethylamino, etc.) ₆ alkylamino groups, etc.), (xiii) 5- to 7-membered cyclic amino groups (for example, having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur atoms in addition to one nitrogen atom) A 5- to 7-membered cyclic amino group (eg, 1-pyrrolidinyl, piperidino, 1-piperazinyl, morpholino, thiomorpholino, etc.), (xiv) a lower alkyl-carbonylamino group (eg, acetylamino, propionylamino, butyrylamino) C _1-6 alkyl-carbonylamino group etc.), (xv) lower alkylsulfonylamino group (for example, methylsulfonylamino group) Bruno, ethylsulfonylamino, propylsulfonyl C _1-6 alkylsulfonylamino group of the amino or the like, etc.), (xvi) lower alkoxy - carbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc. isobutoxycarbonyl C _{1- 6} alkoxy-carbonyl group, etc.), (xvii) carboxy group, (xviii) lower alkyl-carbonyl group (eg, C _1-6 alkyl-carbonyl group such as methylcarbonyl, ethylcarbonyl, butylcarbonyl, etc.), (xix) cyclo Alkyl-carbonyl groups (eg, C _3-6 cycloalkyl-carbonyl groups such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, etc.), (xx) carbamoyl groups, thiocarbamoyl groups, (xxi) mono-lower Alkyl- Rubamoiru group (e.g., methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, mono -C _1-6 alkyl such as butylcarbamoyl - carbamoyl group, etc.), (xxii) di - lower alkyl - carbamoyl group (e.g., diethylcarbamoyl, dibutylcarbamoyl, etc. di -C _1-6 alkyl - carbamoyl group, etc.), (xxiii) lower alkylsulfonyl (e.g., such as C _1-6 alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl, propylsulfonyl), (xxiv) cycloalkylsulfonyl Groups (eg, C _3-6 cycloalkylsulfonyl such as cyclopentylsulfonyl, cyclohexylsulfonyl, etc.), (xxv) phenyl group, (xxvi) naphthyl group, (xxvii) mono-phenyl-lower alkyl groups (eg benzyl, phenylethyl etc.) Mono-phenyl -C _1-6 alkyl group), (xxviii) di-phenyl-lower alkyl group (for example, di-phenyl-C _1-6 alkyl group such as diphenylmethyl, diphenylethyl, etc.), (xxix) mono-phenyl- Lower alkyl-carbonyloxy group (for example, mono-phenyl-C _1-6 alkyl-carbonyloxy group such as phenylmethylcarbonyloxy, phenylethylcarbonyloxy, etc.), (xxx) di-phenyl-lower alkyl-carbonyloxy group (for example, Di-phenyl-C _1-6 alkyl-carbonyloxy group such as diphenylmethylcarbonyloxy and diphenylethylcarbonyloxy), (xxxi) phenoxy group, (xxxii) mono-phenyl-lower alkyl-carbonyl group (eg phenylmethyl) carbonyl, mono- and phenyl ethylcarbonyl - phenyl -C _1-6 Al Le - carbonyl group), (xxxiii) diphenyl - lower alkyl - group (e.g., diphenylmethyl carbonyl, diphenyl -C _1-6 alkyl such as diphenyl ethylcarbonyl - carbonyl group), (xxxiv) benzoyl Group, (xxxv) phenoxycarbonyl group, (xxxvi) phenyl-lower alkyl-carbamoyl group (for example, phenyl-C _1-6 alkyl-carbamoyl group such as phenyl-methylcarbamoyl, phenyl-ethylcarbamoyl, etc.), (xxxvii) phenyl A carbamoyl group, (xxxviii) phenyl-lower alkyl-carbonylamino group (eg, phenyl-C _1-6 alkyl-carbonylamino group such as phenyl-methylcarbonylamino, phenyl-ethylcarbonylamino, etc.), (xxxix) phenyl-lower Alkylamino groups (eg phenyl -Phenyl-C _1-6 alkylamino groups such as methylamino and phenyl-ethylamino), (xxxx) phenyl-lower alkylsulfonyl groups (eg phenyl-C _1- phenyl such as phenyl-methylsulfonyl, phenyl-ethylsulfonyl, etc.) ₆ alkylsulfonyl group, etc.), (xxxxi) phenylsulfonyl group, (xxxxii) phenyl-lower alkylsulfinyl group (for example, phenyl-C _1-6 alkylsulfinyl group such as phenyl-methylsulfinyl, phenyl-ethylsulfinyl, etc.), ( XXXXIII) phenyl - lower alkylsulfonylamino group (e.g., phenyl - methylsulfonylamino, phenyl - ethyl aminosulfonylphenyl -C _1-6 alkylsulfonylamino group of the amino or the like, etc.), (XXXXIV) phenylsulfonylamino groups, (XXXXV) 5 To 7-membered cyclic amino-carboni (E.g., a 5- to 7-membered cyclic amino-carbonyl group which may have 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom in addition to one nitrogen atom (e.g., ( 1-pyrrolidinyl) carbonyl, piperidinocarbonyl, (1-piperazinyl) carbonyl, morpholinocarbonyl, thiomorpholinocarbonyl group, etc.)), (xxxxvi) aminosulfonyl group, (xxxxvii) mono-lower alkylaminosulfonyl group (for example, Mono-C _1-6 alkylaminosulfonyl groups such as methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, butylaminosulfonyl, etc.), (xxxxviii) di-lower alkylaminosulfonyl groups (eg, diethylaminosulfonyl, dibutylaminosulfonyl, etc.) Di-C _1-6 alkylaminosulfonyl group, etc.), (x xxxix) 5- to 7-membered cyclic amino-sulfonyl group (for example, 5- to 7-membered optionally having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur atoms in addition to one nitrogen atom) Cyclic amino-sulfonyl group (eg, (1-pyrrolidinyl) sulfonyl, piperidinosulfonyl, (1-piperazinyl) sulfonyl, morpholinosulfonyl, thiomorpholinosulfonyl group, etc.)), (xxxxx) aminocarbonyloxy group, (xxxxxi) Mono-lower alkylaminocarbonyloxy groups (for example, mono-C _1-6 alkylaminocarbonyloxy groups such as methylaminocarbonyloxy, ethylaminocarbonyloxy, propylaminocarbonyloxy, etc.), (xxxxxii) di-lower alkylaminocarbonyl An oxy group (eg, dimethylaminocarbonyloxy, diethyla Bruno di -C _1-6 alkylamino carbonyloxy groups such carbonyloxy, etc.) and (XXXXXIII) 5 to 7-membered cyclic amino - carbonyl group (e.g., nitrogen atom in addition to one nitrogen atom, oxygen atom and sulfur atom 5- to 7-membered cyclic amino-carbonyloxy group (for example, (1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy, (1-piperazinyl) carbonyl) which may have 1 to 3 heteroatoms selected from Oxy, morpholinocarbonyloxy, thiomorpholinocarbonyloxy group, etc.) (phenyl group, naphthyl group, mono-phenyl-lower alkyl group, di-phenyl-lower alkyl group, mono-phenyl-lower alkyl group, (xxv) to (xxxxiv)) -Lower alkyl-carbonyloxy group, di-phenyl-lower alkyl-carbonyloxy group, phenoxy Mono-phenyl-lower alkyl-carbonyl group, di-phenyl-lower alkyl-carbonyl group, benzoyl group, phenoxycarbonyl group, phenyl-lower alkyl-carbamoyl group, phenylcarbamoyl group, phenyl-lower alkyl-carbonylamino group, phenyl -The lower alkylamino group, the phenyl-lower alkylsulfonyl group, the phenylsulfonyl group, the phenyl-lower alkylsulfinyl group, the phenyl-lower alkylsulfonylamino group, and the phenyl group moiety in the phenylsulfonylamino group further include, for example, a lower alkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, sec- butyl, tert- butyl, pentyl, C _1-6 alkyl hexyl, etc.), lower alkoxy (e.g., methoxy, ethoxy, propoxy Isopropoxy, butoxy, isobutoxy, sec- butoxy, tert C _1-6 alkoxy butoxy, etc.), a halogen atom (e.g., chlorine, bromine, iodine, etc.), hydroxy group, benzyloxy group, an amino group, a mono - lower Alkylamino groups (eg mono-C _1-6 alkylamino etc. such as methylamino, ethylamino, propylamino etc.), di-lower alkylamino groups (eg di-C _1-6 alkylamino such as dimethylamino, diethylamino etc.) Etc.), nitro group, lower alkyl-carbonyl group (for example, C _1-6 alkyl-carbonyl group such as methylcarbonyl, ethylcarbonyl, butylcarbonyl etc.), 1 to 4 substituents selected from benzoyl group, etc. You may do it. ) And the like. The “optionally condensed 5- or 6-membered aromatic ring group” represented by Ar may have 1 to 4, preferably 1 or 2, substituents of (i) to (xxxxxiii).

The above “optionally halogenated lower alkyl group” is, for example, a lower alkyl group (eg, methyl, optionally having 1 to 3 halogen atoms (eg, chloro, bromo, iodo, etc.)). , ethyl, propyl, isopropyl, butyl, sec- butyl, tert- butyl, pentyl, and the like C _1-6 alkyl groups hexyl) and the like, and specific examples include methyl, chloromethyl, difluoromethyl, trichloromethyl , Trifluoromethyl, ethyl, 2-bromoethyl, 2,2,2-trifluoroethyl, propyl, 3,3,3-trifluoropropyl, isopropyl, butyl, 4,4,4-trifluorobutyl, isobutyl, sec -Butyl, tert-butyl, pentyl, isopentyl, neopentyl, 5,5,5-trifluoropentyl, hexyl, 6, Examples include 6,6-trifluorohexyl.
The above “optionally halogenated lower alkoxy group” is, for example, a lower alkoxy group (eg, methoxy, which may have 1 to 3 halogen atoms (eg, chloro, bromo, iodo, etc.)). , Ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, C _1-6 alkoxy groups such as sec-butoxy, tert-butoxy and the like), and specific examples include, for example, methoxy, difluoromethoxy, trifluoromethoxy, ethoxy 2,2,2-trifluoroethoxy, propoxy, isopropoxy, butoxy, 4,4,4-trifluorobutoxy, isobutoxy, sec-butoxy, pentyloxy, hexyloxy and the like.
The above-mentioned “optionally halogenated lower alkylthio group” is, for example, a lower alkylthio group (eg, methylthio) optionally having 1 to 3 halogen atoms (eg, chloro, bromo, iodo, etc.). , Ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, C _1-6 alkylthio groups such as sec-butylthio, tert-butylthio and the like. Specific examples include methylthio, difluoromethylthio, trifluoromethylthio, ethylthio Propylthio, isopropylthio, butylthio, 4,4,4-trifluorobutylthio, isobutylthio, sec-butylthio, tert-butylthio, pentylthio, hexylthio and the like.

As the “substituent” of “represents a 5- or 6-membered aromatic ring group which may be condensed and the aromatic ring group may have a substituent”, (i) an amino group, (ii) Mono-lower alkylamino groups (eg, mono-C _1-6 alkylamino groups such as methylamino, ethylamino, propylamino, etc.), (iii) di-lower alkylamino groups (eg, dimethylamino, diethylamino, etc.) -C _1-6 alkylamino group, etc.), (iv) may have 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur atoms in addition to one nitrogen atom, for example. Membered cyclic amino groups (eg 1-pyrrolidinyl, piperidino, 1-piperazinyl, morpholino, thiomorpholino etc.), (v) lower alkyl-carbonylamino groups (eg acetylamino, propionylamino, buty C _1-6 alkyl such as arylamino - carbonylamino group, etc.), (vi) lower alkylsulfonylamino group (e.g., methylsulfonylamino, ethylsulfonylamino, propylsulfonyl C _1-6 alkylsulfonylamino group of the amino or the like, etc.), (Vii) phenyl-lower alkylamino (eg, phenyl-C _1-6 alkylamino such as phenyl-methylamino, phenyl-ethylamino, etc.), (viii) phenyl-lower alkylsulfonylamino group (eg, phenyl-methylsulfonyl) Amino, phenyl-C _1-6 alkyl-sulfonylamino group such as phenyl-ethylsulfonylamino, etc.), (ix) phenylsulfonylamino group, (x) halogen atom (eg, fluoro, chloro, etc.), (xi) halogenated Optionally substituted lower alkyl groups (eg methyl, ethyl Isopropyl, tert-butyl, trifluoromethyl, etc.), (xii) an optionally halogenated lower alkoxy group (eg, methoxy, ethoxy, isopropoxy, tert-butoxy, trifluoromethoxy, etc.), (xiii) aminosulfonyl Group (xiv) mono-lower alkylaminosulfonyl group (for example, mono-C _1-6 alkylaminosulfonyl group such as methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, butylaminosulfonyl, etc.), (xv) di- Lower alkylaminosulfonyl group (for example, di-C _1-6 alkylaminosulfonyl group such as diethylaminosulfonyl, dibutylaminosulfonyl, (xvi) carbamoyl group, (xvii) mono-lower alkyl-carbamoyl group (for example, methylcarbamoyl, ethyl Carbamoyl, propyl Mono-C _1-6 alkyl-carbamoyl groups such as carbamoyl and butylcarbamoyl), (xviii) di-lower alkyl-carbamoyl groups (eg, di-C _1-6 alkyl-carbamoyl groups such as diethylcarbamoyl and dibutylcarbamoyl) In particular, di-lower alkylamino groups (eg, di-C _1-6 alkylamino groups such as dimethylamino, diethylamino, etc.), nitrogen atoms, oxygen atoms and sulfur atoms in addition to one nitrogen atom A 5- to 7-membered cyclic amino group (for example, 1-pyrrolidinyl, piperidino, 1-piperazinyl, morpholino, thiomorpholino, etc.) optionally having 1 to 3 heteroatoms selected from Good lower alkoxy groups (eg methoxy, ethoxy, isopropoxy, tert-butoxy, trifluoromethoxy, etc.) Aminosulfonyl group, a mono - lower alkylaminosulfonyl group (e.g., methylaminosulfonyl, ethylaminosulfonyl, propyl aminosulfonyl, mono--C _1-6 alkylaminosulfonyl group such as butyl aminosulfonyl, etc.), di - lower alkyl - amino Sulfonyl groups (eg, di-C _1-6 alkylaminosulfonyl groups such as diethylaminosulfonyl, dibutylaminosulfonyl, carbamoyl groups, mono-lower alkyl-carbamoyl groups (eg, methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, butylcarbamoyl, etc.) mono -C _1-6 alkyl - carbamoyl group, etc.), di - lower alkyl - carbamoyl group (e.g., diethylcarbamoyl, di -C _1-6 alkyl, such as dibutylcarbamoyl - carbamoyl group) or the like preferably .

〔式中、Ａ環は置換基を有していてもよいベンゼン環、及びＢ環は置換基を有していてもよい同素環又は複素環を示す。〕で表される基等が挙げられる。
Ａ環の置換基としては、上記のＡｒで示される「縮合していてもよい５または６員芳香環基」の「置換基」等が挙げられ、その置換基数は１ないし３個である。
Ｂ環で示される「置換基を有していてもよい同素環」の「同素環」としては、５ないし９員炭素環（例えば、ベンゼン、シクロペンタン、シクロペンテン、シクロヘキサン、シクロヘキセン、シクロヘキサジエン、シクロヘプタン、シクロヘプテン、シクロヘプタジエン等）等が挙げられる。 As the “5- or 6-membered aromatic ring group” of the “optionally condensed 5- or 6-membered aromatic ring group” represented by Ar, a phenyl group (benzene ring group), a 5- or 6-membered aromatic heterocyclic group, etc. Is mentioned.
The “5- or 6-membered aromatic heterocyclic group” includes, for example, 5 or 6 containing one or more hetero atoms (for example, 1 to 3) selected from a nitrogen atom, a sulfur atom and an oxygen atom in addition to a carbon atom. Membered aromatic heterocyclic groups and the like. Specific examples include thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxadiazolyl, thiadiazolyl, flazanyl and the like.
When the “5- or 6-membered aromatic ring group” of the “optionally condensed 5- or 6-membered aromatic ring group” represented by Ar is, for example, “optionally substituted phenyl group”, the “ As an example in which the “phenyl group” is condensed, for example,
(A) when condensed with a monocyclic homocyclic ring or heterocyclic ring which may have a substituent,
(B) fused with an optionally substituted bicyclic homocyclic or heterocyclic ring, or fused with two identical or different monocyclic homocyclic or heterocyclic rings, and (c) The case where it condenses with the tricyclic homocyclic ring or heterocyclic ring which may have a substituent is mentioned.
Specific examples in which the phenyl group of the above-mentioned (a) “which may be condensed and the phenyl group may have a substituent” is condensed with a monocyclic homocyclic ring or heterocyclic ring For example, the formula

[In formula, A ring shows the benzene ring which may have a substituent, and B ring shows the homocyclic ring or the heterocyclic ring which may have a substituent. The group etc. which are represented by these are mentioned.
Examples of the substituent on the A ring include the “substituent” of the “optionally condensed 5- or 6-membered aromatic ring group” represented by Ar, and the number of substituents is 1 to 3.
The “homocyclic ring” of the “homocyclic ring which may have a substituent” represented by ring B is a 5- to 9-membered carbocyclic ring (for example, benzene, cyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene). , Cycloheptane, cycloheptene, cycloheptadiene, etc.).

The “heterocycle” of the “optionally substituted heterocycle” represented by ring B is, for example, 4 to 14 containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples include a member (preferably 5 to 9 member) aromatic or non-aromatic heterocycle. Specifically, for example, pyridine, pyrazine, pyrimidine, imidazole, furan, thiophene, dihydropyridine, diazepine, oxazepine, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, tetrahydropyran, 1,4-dioxane, piperazine, homo Piperazine, tetrahydrooxazepine, morpholine, thiomorpholine, pyrrole, pyrazole, 1,2,3-triazole, oxazole, oxazolidine, thiazole, thiazolidine, thiadiazolidine, thiadiazinane, isoxazole, imidazoline, imidazolidine, hexahydropyrimidine, etc. Is mentioned. Of these, one heteroatom or a 5- to 9-membered non-aromatic heterocycle containing two heteroatoms that are the same or different (for example, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, tetrahydropyran) 1,4-dioxane, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholine, imidazoline, thiadiazolidine, thiadiazinane, imidazolidine, hexahydropyrimidine and the like. In particular, (1) a non-aromatic heterocyclic ring containing one heteroatom selected from, for example, a nitrogen atom, an oxygen atom and a sulfur atom, and (2) one nitrogen atom and a nitrogen atom, an oxygen atom and a sulfur atom. Non-aromatic heterocycles containing a single hetero atom are preferred.

Examples of the “substituent” of the “homocyclic or heterocyclic ring optionally having substituent (s)” represented by ring B include (i) a halogen atom (for example, fluoro, chloro, bromo, iodo, etc.), ( ii) nitro group, (iii) cyano group, (iv) oxo group, (v) hydroxy group, (vi) lower alkyl group (eg, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec- C _1-6 alkyl group such as butyl) (vii) Lower alkoxy group (for example, C _1-6 alkoxy group such as methoxy, ethoxy, propyloxy, isopropyloxy, butyloxy, etc.), (viii) Lower alkylthio group (for example, , methylthio, ethylthio, and the like C _1-6 alkylthio group such as propylthio), (ix) amino group, (x) mono - lower alkylamino group (e.g., methylamino, ethylamino, propylamino Mono -C _1-6 alkylamino group amino, etc. such), (xi) di - lower alkylamino group (e.g., dimethylamino, and di -C _1-6 alkylamino group diethylamino, etc.), (xii) such as carbon In addition to an atom and one nitrogen atom, a 5- to 7-membered cyclic amino group (for example, 1-pyrrolidinyl, piperidino, optionally having 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur atoms) 1-piperazinyl, morpholino, thiomorpholino, etc.), (xiii) lower alkyl-carbonylamino groups (for example, C _1-6 alkyl-carbonylamino groups such as acetylamino, propionylamino, butyrylamino, etc.), (xiv) lower alkylsulfonyl amino group (e.g., methylsulfonylamino, C _1-6 alkylsulfonylamino group such as ethylsulfonylamino, etc.), (xv) lower a Kokishi - carbonyl group (e.g., methoxycarbonyl, C _1-6 alkoxy, such as ethoxycarbonyl, propoxycarbonyl - such carbonyl group), (xvi) carboxy, (xvii) lower alkylcarbonyl group (e.g., methylcarbonyl, ethylcarbonyl, C _1-6 alkyl-carbonyl group such as propylcarbonyl), (xviii) carbamoyl group, (xix) mono-lower alkylcarbamoyl group (for example, mono-C _1-6 alkyl-carbamoyl group such as methylcarbamoyl, ethylcarbamoyl) Etc.), (xx) di-lower alkylcarbamoyl groups (eg di-C _1-6 alkyl-carbamoyl groups such as dimethylcarbamoyl, diethylcarbamoyl etc.), (xxi) lower alkylsulfonyl groups (eg methylsulfonyl, ethylsulfonyl etc.) , C ₁ such as propylsulfonyl _-6 alkylsulfonyl group, (xxii) aminosulfonyl group, (xxiii) mono-lower alkylaminosulfonyl group (for example, mono-C _1-6 alkyl-aminosulfonyl group such as methylaminosulfonyl, ethylaminosulfonyl, etc.), ( xxiv) 1 to 5 selected from di-lower alkylaminosulfonyl groups (for example, di-C _1-6 alkyl-aminosulfonyl groups such as dimethylaminosulfonyl and diethylaminosulfonyl) and the like are used. Of these, an oxo group, a lower alkyl group (for example, a C _1-6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, etc.) and the like are preferable. Particularly preferred are an oxo group, a C _1-6 alkyl group, a C _1-6 alkyl-carbonylamino group, a C _1-6 alkylsulfonylamino group, and the like.

When the ring B has a nitrogen atom in the ring, for example, the ring B has the formula> N—R ^{1 in the} ring.
[Wherein, R ¹ represents a hydrogen atom, a hydrocarbon group which may have a substituent, an acyl group or a heterocyclic group which may have a substituent. It may have a group represented by Further, the ring B may have 1 to 3 substituents (i) to (xxiv).
The “hydrocarbon group” of the “hydrocarbon group which may have a substituent” represented by R ¹ represents a group obtained by removing one hydrogen atom from a hydrocarbon compound, and examples thereof include the following: Examples thereof include an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, an aralkyl group, and a combination thereof. Of these, C _1-16 hydrocarbon groups and the like are preferable.
(1) Alkyl groups (for example, C _1-6 alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, pentyl, hexyl, etc.)
(2) Alkenyl groups (for example, C _2-6 alkenyl groups such as vinyl, allyl, isopropenyl, butenyl, isobutenyl, sec-butenyl, etc.)
(3) Alkynyl groups (for example, C _2-6 alkynyl groups such as propargyl, ethynyl, butynyl, 1-hexynyl, etc.)
(4) Cycloalkyl groups (for example, C _3-6 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.)
(5) Cross-linked cyclic lower saturated hydrocarbon groups (for example, bicyclo [3.2.1] oct-2-yl, bicyclo [3.3.1] non-2-yl, adamantane-1-yl, etc.) Cyclic C _8-14 saturated hydrocarbon group, etc.)
(6) Aryl group (for example, C _6-14 aryl group such as phenyl, 1-naphthyl, 2-naphthyl, biphenyl, 2-indenyl, 2-anthryl, etc., preferably phenyl group)
(7) Aralkyl groups (for example, phenyl-C _1-10 alkyl such as benzyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl, phenylhexyl; naphthyl-C _1-6 alkyl such as α-naphthylmethyl; diphenylmethyl And C _7-16 aralkyl groups such as diphenyl-C _1-3 alkyl such as diphenylethyl)
(8) aryl-alkenyl groups (eg C _6-14 aryl-C such as phenyl-C _2-12 alkenyl such as styryl, cinnamyl, 4-phenyl-2-butenyl, 4-phenyl-3-butenyl, etc.) _2-12 alkenyl group, etc.)
(9) aryl-C _2-12 alkynyl group (eg, C _6-14 ant such as phenyl-C _2-12 alkynyl such as phenylethynyl, 3-phenyl-2-propynyl, 3-phenyl-1-propynyl, etc. _-Lu- C _2-12 alkynyl group, etc.)
(10) Cycloalkyl-alkyl groups (for example, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptylethyl, cyclopropylpropyl) , Cyclobutylpropyl, cyclopentylpropyl, cyclohexylpropyl, cycloheptylpropyl, cyclopropylbutyl, cyclobutylbutyl, cyclopentylbutyl, cyclohexylbutyl, cycloheptylbutyl, cyclopropylpentyl, cyclobutylpentyl, cyclopentylpentyl, cyclohexylpentyl, cycloheptylpentyl , Cyclopropyl hexyl, cyclobutyl hexyl, cyclopentyl hex Le, like C _3-7 cycloalkyl -C _1-6 alkyl group such as cyclohexyl hexyl)
(11) Aryl-aryl-C _1-10 alkyl group (for example, biphenylmethyl, biphenylethyl, etc.)

Preferred examples of the “hydrocarbon group” of the “hydrocarbon group optionally having substituent (s)” represented by R ¹ include a C _1-6 alkyl group, a C _3-6 cycloalkyl group, C _{7 -16} aralkyl group and the like. More preferably C _7-10 aralkyl group (e.g., benzyl, phenylethyl, phenyl--C _1-4 alkyl such as phenylpropyl), and the like.
Examples of the “substituent” of the “hydrocarbon group optionally having substituent (s)” represented by R ¹ include (i) a halogen atom (eg, fluoro, chloro, bromo, iodo, etc.), (ii) Nitro group, (iii) cyano group, (iv) oxo group, (v) hydroxy group, (vi) optionally halogenated lower (C _1-6 ) alkyl group, (vii) halogenated Good lower (C _1-6 ) alkoxy groups, (viii) optionally halogenated lower (C _1-6 ) alkylthio groups, (ix) amino groups, (x) mono-lower alkylamino groups (eg methyl Mono-C _1-6 alkylamino groups such as amino, ethylamino, propylamino, etc.), (xi) di-lower alkylamino groups (eg, di-C _1-6 alkylamino groups such as dimethylamino, diethylamino, etc.) , (Xii) for example carbon atoms and one nitrogen atom or less In addition, a 5- to 7-membered cyclic amino group (for example, 1-pyrrolidinyl, piperidino, 1-piperazinyl, morpholino, thio) optionally having 1 to 3 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom Morpholino etc.), (xiii) lower alkyl-carbonylamino groups (eg C _1-6 alkyl-carbonylamino groups such as acetylamino, propionylamino, butyrylamino etc.), (xiv) lower alkylsulfonylamino groups (eg methylsulfonyl) C _1-6 alkyl-sulfonylamino groups such as amino and ethylsulfonylamino), (xv) lower alkoxy-carbonyl groups (for example, C _1-6 alkoxy-carbonyl groups such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, etc.) , (Xvi) carboxy group, (xvii) lower alkyl-carbonyl (E.g., methylcarbonyl, ethylcarbonyl, C _1-6 alkyl, such as propyl carbonyl - carbonyl group), (xviii) carbamoyl group, a thiocarbamoyl group, (xix) mono - lower alkyl - carbamoyl group (e.g., methylcarbamoyl, Mono-C _1-6 alkyl-carbamoyl groups such as ethylcarbamoyl), (xx) di-lower alkyl-carbamoyl groups (eg, di-C _1-6 alkyl-carbamoyl groups such as dimethylcarbamoyl, diethylcarbamoyl), (Xxi) a lower alkylsulfonyl group (eg, a C _1-6 alkylsulfonyl group such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, etc.), (xxii) a lower alkoxy-carbonyl-lower alkyl group (eg, methoxycarbonylmethyl, ethoxycarbonyl) Methyl, tert-butoxycarbo Rumechiru, methoxycarbonylethyl, methoxycarbonylmethyl, methoxycarbonyl (dimethyl) methyl, ethoxycarbonyl (dimethyl) methyl, tert- butoxycarbonyl (dimethyl) C _1-6 alkyl such as methyl - carbonyl -C _1-6 alkyl group) , (Xxiii) carboxy-lower alkyl group (for example, carboxy-C _1-6 alkyl group such as carboxymethyl, carboxyethyl, carboxy (dimethyl) methyl, etc.), (xxiv) an optionally substituted heterocyclic ring Group (xxv) C _6-14 aryl group (eg phenyl, naphthyl etc.), (xxvi) C _7-16 aralkyl group (eg benzyl etc.), (xxvii) substituent (eg C _1-4 alkyl, Halogeno C _1-4 alkyl, C _6-10 aryl, halogeno C _6-10 aryl, C _1-4 alkyl-C _6-10 aryl, halogeno C _1-4 a A ureido group (eg, ureido, 3-methylureido, 3-ethylureido, 3-phenyl) which may have an alkyl group such as rualkyl-C _6-10 aryl, C _1-4 alkoxy-C _6-10 aryl, benzyl and the like. Ureido, 3- (4-fluorophenyl) ureido, 3- (2-methylphenyl) ureido, 3- (4-methoxyphenyl) ureido, 3- (2,4-difluorophenyl) ureido, 3- [3,5 -Bis (trifluoromethyl) phenyl] ureido, 3-benzylureido, 3- (1-naphthyl) ureido, 3- (2-biphenylyl) ureido, etc.), (xxviii) substituents (eg C _1-4 alkyl, Halogeno C _1-4 alkyl, C _6-10 aryl, halogeno C _6-10 aryl, C _1-4 alkyl-C _6-10 aryl, halogeno C _1-4 alkyl-C _6-10 aryl, C _1-4 alkoxy -C _6-10 A thioureido group (for example, thioureido, 3-methylthioureido, 3-ethylthioureido, 3-phenylthioureido, 3- (4-fluorophenyl) thioureido, 3- (4 -Methylphenyl) thioureido, 3- (4-methoxyphenyl) thioureido, 3- (2,4-dichlorophenyl) thioureido, 3-benzylthioureido, 3- (1-naphthyl) thioureido, etc.), (xxix) substituent ( For example, an amidino group (for example, amidino, N ¹ -methylamidino, which may have one or two selected from C _1-4 alkyl, C _6-10 aryl, nitro-C _6-10 aryl, etc.) N ¹ -ethylamidino, N ¹ -phenylamidino, N ¹ , N ¹ -dimethylamidino, N ¹ , N ² -dimethylamidino, N ¹ -me Chill -N ¹ - Echiruamijino, N ^1, N ¹ - diethyl amidino, N ¹ - methyl -N ¹ - phenyl-amidino, N ^1, N ¹ - di (4-nitrophenyl) amidino, etc.), (xxx) substituent A guanidino group (for example, guanidino, 3-methylguanidino, etc.) optionally having (for example, 1-2 selected from C _1-4 alkyl, C _6-10 aryl, nitro-C _6-10 aryl, etc.) 3,3-dimethylguanidino, 3,3-diethylguanidino, etc.), (xxxi) substituents (eg, C _1-4 alkyl, halogeno C _1-4 alkyl, C _6-10 aryl, halogeno C _6-10 aryl, C _1-4 alkyl-C _6-10 aryl, halogeno C _1-4 alkyl-C _6-10 aryl, C _1-4 alkoxy-C _6-10 aryl, nitro-C _6-10 aryl, benzyl, halogenobenzyl, Benzoyl, halogenobenzoyl, etc.) Cyclic aminocarbonyl groups such as (1-pyrrolidinyl) carbonyl, piperidinocarbonyl, (4-methylpiperidino) carbonyl, (4-phenylpiperidino) carbonyl, (4-benzylpiperidino) carbonyl, (4 -Benzoylpiperidino) carbonyl, [4- (4-fluorobenzoyl) piperidino] carbonyl, (4-methyl-1-piperazinyl) carbonyl, (4-phenyl-1-piperazinyl) carbonyl, [4- (4-nitro Phenyl) -1-piperazinyl] carbonyl, (4-benzyl-1-piperazinyl) carbonyl, morpholinocarbonyl, thiomorpholinocarbonyl, etc.), (xxxii) substituents (eg, C _1-4 alkyl, C _6-10 aryl, etc.) An aminothiocarbonyl group (for example, aminothiocarbo group) which may have 1 to 2 selected Le, methylamino thiocarbonyl, dimethylaminothiocarbonyl, etc.), (xxxiii) substituent (e.g., C _1-4 alkyl, optionally having one or two) selected from C _6-10 aryl and amino Sulfonyl group (eg, aminosulfonyl, methylaminosulfonyl, dimethylaminosulfonyl, etc.), (xxxiv) substituent (eg, halogen atom, C _1-4 alkyl, halogeno C _1-4 alkyl, C _1-4 alkoxy, nitro, Phenylsulfonylamino (eg, phenylsulfonylamino, (4-methylphenyl) sulfonylamino, (4-chlorophenyl) sulfonylamino) optionally having 1-2 selected from C _1-4 alkyl-carbonylamino and the like , (2,5-dichlorophenyl) sulfonylamino, (4-methoxyphenyl) sulfonylamino, (4- Cetyl aminophenyl) sulfonylamino, (4-nitrophenyl) phenylsulfonylamino, etc.), (xxxv) sulfo group, (xxxvi) sulfino group, (xxxvii) sulfeno group, (xxxviii) C _1-6 alkylsulfonyl group (e.g., Mechirusuruho, Echirusuruho, propylsulfonyl etc.), (xxxix) C _1-6 alkylsulfenyl fino group (e.g., methylsulfinyl Fino, ethylsulfamoyl Fino, propylsulfanyl Fino, etc.), (xxxx) C _1-6 alkylsulfenyl phenol group (e.g. , Methylsulfeno, ethylsulfeno, propylsulfeno, etc.), (xxxxi) phosphono group, (xxxxii) di-C _1-6 alkoxyphosphoryl group (eg, dimethoxyphosphoryl, diethoxyphosphoryl, dipropoxyphosphoryl, etc.), xxxxiii) aminocarbonyloxy group, (xxxxxi) mono-lower alkylaminocarbonyloxy (E.g., methylamino carbonyloxy, ethylamino carbonyloxy, mono- -C _1-6 alkylaminocarbonyl group and propyl aminocarbonyloxy, etc.), (XXXXXII) di - lower alkylaminocarbonyl group (e.g., dimethylaminocarbonyl Di-C _1-6 alkylaminocarbonyloxy groups such as oxy, diethylaminocarbonyloxy and the like) and (xxxxxiii) 5- to 7-membered cyclic amino-carbonyloxy groups (for example, nitrogen atom, oxygen atom and 5- to 7-membered cyclic amino-carbonyloxy group (eg, (1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy, (1-piperazinyl) which may have 1 to 3 heteroatoms selected from sulfur atom and the like ) Carbonyloxy, morpholinocarbonyloxy, thio It Le morpholinocarbonyl group, etc.), etc.) 1 selected from such five (preferably 1 to 3) can be mentioned.

Of these, a halogen atom, an optionally halogenated C _1-6 alkyl group, an optionally halogenated C _1-6 alkoxy group, a hydroxy group, a nitro group, a cyano group, a carboxy group, C _{1 -6} alkoxy-carbonyl group, carbamoyl group, aminothiocarbonyl group, mono-C _1-6 alkyl-carbamoyl group, di-C _1-6 alkyl-carbamoyl group, amino group, mono-C _1-6 alkylamino group, Di-C _1-6 alkylamino group, 5- to 7-membered cyclic amino group, C _1-6 alkyl-carbonylamino group, aminosulfonyl group, mono-C _1-6 alkylaminosulfonyl group, di-C _1-6 alkyl Examples include an aminosulfonyl group, a phenylsulfonylamino group, a C _1-6 alkylsulfonylamino group, and the like.

Examples of the “heterocyclic group” of the “(xxiv) optionally substituted heterocyclic group” include 1 to 6 heteroatoms (preferably 1) selected from a nitrogen atom, an oxygen atom and a sulfur atom. Or a group formed by removing one hydrogen atom from a 5- to 14-membered (monocyclic or bicyclic to tetracyclic) heterocyclic ring.
Monocyclic heterocyclic groups include pyridine, pyrazine, pyrimidine, imidazole, furan, thiophene, dihydropyridine, diazepine, oxazepine, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, piperazine, homopiperazine, tetrahydrooxazepine , Morpholine, thiomorpholine, pyrrole, pyrazole, 1,2,3-triazole, oxazole, oxazolidine, thiazole, thiazolidine, isoxazole, imidazoline, triazole, thiadiazole, oxadiazole, oxathiadiazole, triazine, tetrazole, etc. And a group formed by removing one hydrogen atom from a heterocyclic ring.
Examples of the bicyclic heterocycle include indole, dihydroindole, isoindole, dihydroisoindole, benzofuran, dihydrobenzofuran, benzimidazole, benzoxazole, benzisoxazole, benzothiazole, indazole, quinoline, tetrahydroquinoline, isoquinoline, tetrahydro Isoquinoline, tetrahydro-1H-1-benzazepine, tetrahydro-1H-2-benzazepine, tetrahydro-1H-3-benzazepine, tetrahydrobenzoxazepine, quinazoline, tetrahydroquinazoline, quinoxaline, tetrahydroquinoxaline, benzodioxan, benzodioxole, A group formed by removing one hydrogen atom from a bicyclic heterocyclic ring such as benzothiazine or imidazopyridine is used.
As a 3 or 4 ring heterocyclic group, one hydrogen atom can be removed from a 3 or 4 ring heterocyclic ring such as acridine, tetrahydroacridine, pyrroloquinoline, pyrroloindole, cyclopentoindole, isoindolobenzazepine, etc. Groups and the like.
The “heterocyclic group” is preferably a group formed by removing one hydrogen atom from a monocyclic or bicyclic heterocyclic ring.
The “substituent” of the “heterocyclic group optionally having substituent (s)” is the “substituent” of the “homocyclic ring or heterocyclic ring optionally having substituent (s)” represented by the ring B above. The number of substituents is 1 to 5.

The “optionally substituted hydrocarbon group” represented by R ¹ is preferably a halogen atom, C _1-6 alkyl, C _1-6 alkoxy, nitro, cyano, carbamoyl, mono-C _1-6. 1 to 5 substituents selected from alkyl-carbamoyl, di-C _1-6 alkyl-carbamoyl, aminosulfonyl, mono-C _1-6 alkylaminosulfonyl, di-C _1-6 alkylaminosulfonyl and hydroxy An _optionally substituted C _7-16 aralkyl group (preferably benzyl and the like) and the like.
Examples of the “acyl group” represented by R ¹ include, for example, the formula:
^{- (C = O) -R 2} , - (C = O) -OR 2, - (C = O) -NR 2 R 3, -SO 2 -R 2, -SO-R 2, -SO 2 -NR ² R ³ , — (C═S) —OR ² or — (C═S) NR ² R ³
[Wherein R ² and R ³ each represent (i) a hydrogen atom, (ii) a hydrocarbon group optionally having substituent (s) or (iii) a heterocyclic group optionally having substituent (s)). R ² and R ³ may be bonded to each other to form a nitrogen-containing cyclic group which may have a substituent together with the adjacent nitrogen atom. And the like.
Of these, the formula: — (C═O) —R ² , — (C═O) —NR ² R ³ , —SO ₂ —R ² , or —SO ₂ —NR ² R ³ [wherein, The symbols are as defined above. An acyl group represented by the formula:

で表される基等が挙げられる。
該「置換基を有していてもよい含窒素環基」の「置換基」としては、上記Ｂ環で示される「置換基を有していてもよい同素環又は複素環」の「置換基」と同様のものが挙げられ、その置換基数は１ないし５個である。
Ｒ²及びＲ³として、好ましくは、（i）水素原子、（ii）ハロゲン化されていてもよいＣ_1-6アルキル、（iii）Ｃ_1-6アルキル及びＣ_1-6アルコキシから選ばれる置換基を１ないし３個有していてもよいＣ_6-10アリール、（iii）Ｃ_7-16アラルキル（例、ベンジル等）、（iv）５又は６員複素環基（例、ピリジル、チエニル、フリル等）等が挙げられる。
上記Ｒ¹で示される「アシル基」として、好ましくは、ホルミル、ハロゲン化されていてもよいＣ_1-6アルキル−カルボニル（例、アセチル、トリフルオロアセチル、プロピオニル等）、５又は６員複素環カルボニル（例、ピリジルカルボニル、チエニルカルボニル、フリルカルボニル等）、Ｃ_6-14アリール−カルボニル（例、ベンゾイル、１−ナフトイル、２−ナフトイル等）、Ｃ_7-16アラルキル−カルボニル（例、フェニルアセチル、３−フェニルプロピオニル等）、ハロゲン化されていてもよいＣ_1-6アルキルスルホニル（例、メタンスルホニル、トリフルオロメタンスルホニル、プロピルスルホニル等）、Ｃ_6-14アリールスルホニル（例、ベンゼンスルホニル、ナフチルスルホニル等）、カルバモイル、モノ−Ｃ_1-6アルキル−カルバモイル（例、メチルカルバモイル、エチルカルバモイル等）、Ｃ_1-6アルキル−カルバモイル（例、ジメチルカルバモイル、ジエチルカルバモイル等）、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル（例、メチルアミノスルホニル、エチルアミノスルホニル等）、ジ−Ｃ_1-6アルキルアミノスルホニル（例、ジメチルアミノスルホニル、ジエチルアミノスルホニル等）等が挙げられる。
Ｒ¹は、好ましくは、水素原子、Ｃ_1-6アルキル、Ｃ_1-6アルキル−カルボニル、カルバモイル、モノ−Ｃ_1-6アルキル−カルバモイル、ジ−Ｃ_1-6アルキル−カルバモイル、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル、ジ−Ｃ_1-6アルキルアミノスルホニル等である。 The “hydrocarbon group optionally having substituent (s)” represented by R ² or R ³ and the “heterocyclic group optionally having substituent (s)” are the “having substituents” represented by R ¹ above. And the same as “optionally substituted hydrocarbon group” and “optionally substituted heterocyclic group”.
The “nitrogen-containing cyclic group which may have a substituent” formed by R ² and R ³ is selected from, for example, a nitrogen atom, an oxygen atom and a sulfur atom in addition to a carbon atom and one nitrogen atom. And 5- to 9-membered (preferably 5- to 7-membered) nitrogen-containing saturated heterocyclic group which may contain 1 to 3 heteroatoms. More specifically, for example, the formula

The group etc. which are represented by these are mentioned.
As the “substituent” of the “nitrogen-containing ring group optionally having substituent (s)”, the “substitution” of the “homocyclic ring or heterocycle optionally having substituent (s)” represented by the above ring B And the like, and the number of substituents is 1 to 5.
R ² and R ³ are preferably a substituent selected from (i) a hydrogen atom, (ii) an optionally halogenated C _1-6 alkyl, (iii) C _1-6 alkyl and C _1-6 alkoxy C _6-10 aryl _optionally having 1 to 3 groups, (iii) C _7-16 aralkyl (eg, benzyl etc.), (iv) 5 or 6-membered heterocyclic group (eg, pyridyl, thienyl, Frills, etc.).
The “acyl group” represented by R ¹ is preferably formyl, optionally halogenated C _1-6 alkyl-carbonyl (eg, acetyl, trifluoroacetyl, propionyl, etc.), 5- or 6-membered heterocycle. Carbonyl (eg, pyridylcarbonyl, thienylcarbonyl, furylcarbonyl, etc.), C _6-14 aryl-carbonyl (eg, benzoyl, 1-naphthoyl, 2-naphthoyl, etc.), C _7-16 aralkyl-carbonyl (eg, phenylacetyl, 3-phenylpropionyl, etc.), optionally halogenated C _1-6 alkylsulfonyl (eg, methanesulfonyl, trifluoromethanesulfonyl, propylsulfonyl, etc.), C _6-14 arylsulfonyl (eg, benzenesulfonyl, naphthylsulfonyl, etc.) ), carbamoyl, mono--C _1-6 alkyl - Karubamoi (Eg, methylcarbamoyl, ethylcarbamoyl, etc.), C _1-6 alkyl - carbamoyl (e.g., dimethylcarbamoyl, diethylcarbamoyl, etc.), aminosulfonyl, mono--C _1-6 alkylaminosulfonyl (eg, methylaminosulfonyl, ethylamino Sulfonyl), di-C _1-6 alkylaminosulfonyl (eg, dimethylaminosulfonyl, diethylaminosulfonyl, etc.) and the like.
R ¹ is preferably a hydrogen atom, C _1-6 alkyl, C _1-6 alkyl-carbonyl, carbamoyl, mono-C _1-6 alkyl-carbamoyl, di-C _1-6 alkyl-carbamoyl, aminosulfonyl, mono -C _1-6 alkylaminosulfonyl, di -C _1-6 alkylamino-sulfonyl or the like.

で表される基の具体例としては、ナフタレン；テトラヒドロナフタレン；インダン；インデン；ベンゾ[a]シクロヘプテン；２，３−ジヒドロ−１−ベンゾフラン、１，３−ジヒドロ−２−ベンゾフラン等のベンゾフラン；クロマン；３，４−ジヒドロ−１Ｈ−イソクロメン；２，３，４，５−テトラヒドロ−１−ベンゾオキセピン、１，３，４，５−テトラヒドロ−２−ベンゾオキセピン、１，２，４，５−テトラヒドロ−３−ベンゾオキセピン等のベンゾオキセピン；２，３−ジヒドロ−１−ベンゾチオフェン、１，３−ジヒドロ−２−ベンゾチオフェン等のベンゾチオフェン；チオクロマン；３，４−ジヒドロ−１Ｈ−イソチオクロメン；２，３，４，５−テトラヒドロ−１−ベンゾチエピン、１，３，４，５−テトラヒドロ−２−ベンゾチエピン、１，２，４，５−テトラヒドロ−３−ベンゾチエピン等のベンゾチエピン；３，４−ジヒドロ−２Ｈ−１−ベンゾチオピラン；２,３−ジヒドロ−１Ｈ−インドール；１,２,３,４−テトラヒドロキノリン；２,３−ジヒドロ−１Ｈ−イソインドール；１,２,３,４−テトラヒドロイソキノリン；２,３,４,５−テトラヒドロ−１Ｈ−１−ベンズアゼピン、２,３,４,５−テトラヒドロ−１Ｈ−２−ベンズアゼピン、２,３,４,５−テトラヒドロ−１Ｈ−３−ベンズアゼピン等のベンズアゼピン；１,２,３,４,５,６−ヘキサヒドロ−１−ベンズアゾシン、１,２,３,４,５,６−ヘキサヒドロ−２−ベンズアゾシン、１,２,３,４,５,６−ヘキサヒドロ−３−ベンズアゾシン等のベンズアゾシン；２,３,４,５,６,７−ヘキサヒドロ−１Ｈ−１−ベンズアゾニン、２,３,４,５, ６,７−ヘキサヒドロ−１Ｈ−２−ベンズアゾニン、２,３,４,５,６,７−ヘキサヒドロ−１Ｈ−３−ベンズアゾニン、２,３,４,５,６,７−ヘキサヒドロ−１Ｈ−４−ベンズアゾニン等のベンズアゾニン；２，３−ジヒドロベンズオキサゾール等のベンズオキサゾール；２，３−ジヒドロベンゾチアゾール等のベンゾチアゾール；２，３−ジヒドロ−１，２−ベンズイソチアゾール、１，３−ジヒドロ−２，１−ベンズイソチアゾール等のベンズイソチアゾール；２，３−ジヒドロ−１Ｈ−ベンズイミダゾール等のベンズイミダゾール；１，３−ジヒドロ−２，１，３−ベンゾチアジアゾール；３，４−ジヒドロ−１Ｈ−２，１−ベンズオキサジン、３，４−ジヒドロ−１Ｈ−２，３−ベンズオキサジン、３，４−ジヒドロ−２Ｈ−１，２−ベンズオキサジン、３，４−ジヒドロ−２Ｈ−１，４−ベンズオキサジン、３，４−ジヒドロ−２Ｈ−１，３−ベンズオキサジン、３，４−ジヒドロ−２Ｈ−３，１−ベンズオキサジン等のベンズオキサジン；３，４−ジヒドロ−１Ｈ−２，１−ベンゾチアジン、３，４−ジヒドロ−１Ｈ−２，３−ベンゾチアジン、３，４−ジヒドロ−２Ｈ−１，２−ベンゾチアジン、３，４−ジヒドロ−２Ｈ−１，４−ベンゾチアジン、３，４−ジヒドロ−２Ｈ−１，３−ベンゾチアジン、３，４−ジヒドロ−２Ｈ−３，１−ベンゾチアジン等のベンゾチアジン；３，４−ジヒドロ−２Ｈ−１，２−ベンゾイソチアジン、３，４−ジヒドロ−１Ｈ−２，１−ベンゾイソチアジン等のベンゾイソチアジン；３，４−ジヒドロ−１Ｈ−２，１３−ベンゾチアジアジン；１，２，３，４−テトラヒドロシンノリン、１，２，３，４−テトラヒドロフタラジン、１，２，３，４−テトラヒドロキナゾリン、１，２，３，４−テトラヒドロキノキサリン等のベンゾジアジン；３，４−ジヒドロ−１，２−ベンズオキサチイン、３，４−ジヒドロ−２，１−ベンズオキサチイン、２，３−ジヒドロ−１，４−ベンズオキサチイン、１，４−ジヒドロ−２，３−ベンズオキサチイン、４Ｈ−１，３−ベンズオキサチイン、４Ｈ−３，１−ベンズオキサチイン等のベンズオキサチイン；１，３−ベンゾジオキソール；１，３−ベンゾジチオール；３，４−ジヒドロ−１，２−ベンゾジオキシン、２，３−ジヒドロ−１，４−ベンゾジオキシン、１，４−ジヒドロ−２，３−ベンゾジオキシン、４Ｈ−１，３−ベンゾジオキシン等のベンゾジオキシン；３，４−ジヒドロ−１，２−ベンズジチイン、２，３−ジヒドロ−１，４−ベンズジチイン、１，４−ジヒドロ−２，３−ベンズジチイン、４Ｈ−１，３−ベンズジチイン等のベンズジチイン；２，３，４，５−テトラヒドロ−１，２−ベンズオキサゼピン、２，３，４，５−テトラヒドロ−１，３−ベンズオキサゼピン、２，３，４，５−テトラヒドロ−１，４−ベンズオキサゼピン、２，３，４，５−テトラヒドロ−１，５−ベンズオキサゼピン、１，３，４，５−テトラヒドロ−２，１−ベンズオキサゼピン、１，３，４，５−テトラヒドロ−２，３−ベンズオキサゼピン、１，３，４，５−テトラヒドロ−２，４−ベンズオキサゼピン、１，２，４，５−テトラヒドロ−３，１−ベンズオキサゼピン、１，２，４，５−テトラヒドロ−３，２−ベンズオキサゼピン、１，２，３，５−テトラヒドロ−４，１−ベンズオキサゼピン等のベンズオキサゼピン；２，３，４，５−テトラヒドロ−１，２−ベンゾチアゼピン、２，３，４，５−テトラヒドロ−１，４−ベンゾチアゼピン、２，３，４，５−テトラヒドロ−１，５−ベンゾチアゼピン、１，３，４，５−テトラヒドロ−２，１−ベンゾチアゼピン、１，３，４，５−テトラヒドロ−２，４−ベンゾチアゼピン、１，２，４，５−テトラヒドロ−３，１−ベンゾチアゼピン、１，２，４，５−テトラヒドロ−３，２−ベンゾチアゼピン、１，２，３，５−テトラヒドロ−４，１−ベンゾチアゼピン等のベンゾチアゼピン；２，３，４，５−テトラヒドロ−１Ｈ−１，２−ベンゾチアゼピン、２，３，４，５−テトラヒドロ−１Ｈ−１，３−ベンゾジアゼピン、２，３，４，５−テトラヒドロ−１Ｈ−１，４−ベンゾジアゼピン、２，３，４，５−テトラヒドロ−１Ｈ−１，５−ベンゾジアゼピン、２，３，４，５−テトラヒドロ−１Ｈ−２，３−ベンゾジアゼピン、２，３，４，５−テトラヒドロ−１Ｈ−２，４−ベンゾジアゼピン等のベンゾジアゼピン；４，５−ジヒドロ−１，３−ベンゾジオキセピン、４，５−ジヒドロ−３Ｈ−１，２−ベンゾジオキセピン、２，３−ジヒドロ−５Ｈ−１，４−ベンゾジオキセピン、３，４−ジヒドロ−２Ｈ−１，５−ベンゾジオキセピン、４，５−ジヒドロ−１Ｈ−２，３−ベンゾジオキセピン、１，５−ジヒドロ−２，４−ベンゾジオキセピン等のベンゾジオキセピン；４，５−ジヒドロ−１Ｈ−２，３−ベンゾチエピン、１，５−ジヒドロ−２，４−ベンゾジチエピン、３，４−ジヒドロ−２Ｈ−１，５−ベンゾジチエピン、２，３−ジヒドロ−５Ｈ−１，４−ベンゾジチエピン等のベンゾジチエピン、３，４，５，６−テトラヒドロ−２Ｈ−１，５−ベンズオキサゾシン、３，４，５，６−テトラヒドロ−２Ｈ−１，６−ベンズオキサゾシン等のベンズオキサゾシン；３，４，５，６−テトラヒドロ−２Ｈ−１，５−ベンゾチアゾシン、３，４，５，６−テトラヒドロ−２Ｈ−１，６−ベンゾチアゾシン等のベンゾチアゾシン；１，２，３，４，５，６−ヘキサヒドロ−１，６−ベンゾジアゾシン等のベンゾジアゾシン；２，３，４，５−テトラヒドロ−１，６−ベンズオキサチオシン等のベンズオキサチオシン；２，３，４，５−テトラヒドロ−１，６−ベンゾジオキソシン等のベンゾジオキソシン；１，３，５−ベンゾトリオキセピン、５Ｈ−１，３，４−ベンゾトリオキセピン等のベンゾトリオキセピン；３，４−ジヒドロ−１Ｈ−５，２，１−ベンズオキサチアゼピン、３，４−ジヒドロ−２Ｈ−５，１，２−ベンズオキサチアゼピン、４，５−ジヒドロ−３，１，４−ベンズオキサチアゼピン、４，５−ジヒドロ−３Ｈ−１，２，５−ベンズオキサチアゼピン等のベンズオキサチアゼピン；２，３，４，５−テトラヒドロ−１，３，４−ベンズオキサジアゼピン等のベンズオキサジアゼピン；２，３，４，５−テトラヒドロ−１，３，５−ベンズチアジアゼピン等のベンズチアジアゼピン；２，３，４，５−テトラヒドロ−１Ｈ−１，２，５−ベンゾトリアゼピン等のベンゾトリアゼピン；４，５−ジヒドロ−１，３，２−ベンゾオキサチエピン、４，５−ジヒドロ−１Ｈ−２，３−ベンズオキサチエピン、３，４−ジヒドロ−２Ｈ−１，５−ベンズオキサチエピン、４，５−ジヒドロ−３Ｈ−１，２−ベンズオキサチエピン、４，５−ジヒドロ−３Ｈ−２，１−ベンズオキサチエピン、２，３−ジヒドロ−５Ｈ−１，４−ベンズオキサチエピン、２，３−ジヒドロ−５Ｈ−４，１−ベンズオキサチエピン等、とりわけナフタレン、テトラヒドロナフタレン、インダン、インデン、２,３,４,５−テトラヒドロ−１Ｈ−３−ベンズアゼピン、２,３,４,５−テトラヒドロ−１Ｈ−２−ベンズアゼピン、２,３−ジヒドロ−１Ｈ−インドール、２,３,４,５−テトラヒドロ−１,４−ベンズオキサゼピン、２，３−ジヒドロ−１−ベンゾフラン、クロマン、１，３−ジヒドロ−２H−ベンゾイミダゾール−２−オン、１，３−ジヒドロ−２，１，３−ベンゾチアジアゾール等の２環式縮合ベンゼン環から水素原子を１個除去してできる基等が挙げられる。 Above formula

Specific examples of the group represented by the formula: naphthalene; tetrahydronaphthalene; indane; indene; benzo [a] cycloheptene; benzofuran such as 2,3-dihydro-1-benzofuran and 1,3-dihydro-2-benzofuran; 3,4-dihydro-1H-isochromene; 2,3,4,5-tetrahydro-1-benzoxepin, 1,3,4,5-tetrahydro-2-benzoxepin, 1,2,4,5-tetrahydro-3 -Benzoxepin such as benzoxepin; benzothiophene such as 2,3-dihydro-1-benzothiophene, 1,3-dihydro-2-benzothiophene; thiochroman; 3,4-dihydro-1H-isothiochromene; 5-tetrahydro-1-benzothiepine, 1,3,4,5-tetrahydro-2-ben Benzothiepine such as thiepine, 1,2,4,5-tetrahydro-3-benzothiepine; 3,4-dihydro-2H-1-benzothiopyran; 2,3-dihydro-1H-indole; 1,2,3,4-tetrahydro 2,3-dihydro-1H-isoindole; 1,2,3,4-tetrahydroisoquinoline; 2,3,4,5-tetrahydro-1H-1-benzazepine, 2,3,4,5-tetrahydro- Benzazepines such as 1H-2-benzazepine, 2,3,4,5-tetrahydro-1H-3-benzazepine; 1,2,3,4,5,6-hexahydro-1-benzazocine, 1,2,3,4 , 5,6-hexahydro-2-benzazocine, benzazocine such as 1,2,3,4,5,6-hexahydro-3-benzazocine; 2,3,4,5,6,7-hexahydro-1H-1- Benzua Nin, 2,3,4,5,6,7-hexahydro-1H-2-benzazonin, 2,3,4,5,6,7-hexahydro-1H-3-benzazonin, 2,3,4,5, Benzazonin such as 6,7-hexahydro-1H-4-benzazonin; benzoxazole such as 2,3-dihydrobenzoxazole; benzothiazole such as 2,3-dihydrobenzothiazole; 2,3-dihydro-1,2-benz Benzisothiazoles such as isothiazole and 1,3-dihydro-2,1-benzisothiazole; benzimidazoles such as 2,3-dihydro-1H-benzimidazole; 1,3-dihydro-2,1,3-benzo Thiadiazole; 3,4-dihydro-1H-2,1-benzoxazine, 3,4-dihydro-1H-2,3-benzoxazine, 3,4-dihydro- H-1,2-benzoxazine, 3,4-dihydro-2H-1,4-benzoxazine, 3,4-dihydro-2H-1,3-benzoxazine, 3,4-dihydro-2H-3,1 A benzoxazine such as benzoxazine; 3,4-dihydro-1H-2,1-benzothiazine, 3,4-dihydro-1H-2,3-benzothiazine, 3,4-dihydro-2H-1,2-benzothiazine, Benzothiazines such as 3,4-dihydro-2H-1,4-benzothiazine, 3,4-dihydro-2H-1,3-benzothiazine, 3,4-dihydro-2H-3,1-benzothiazine; 3,4-dihydro Benzoisothiazines such as -2H-1,2-benzisothiazine, 3,4-dihydro-1H-2,1-benzisothiazine; 3,4-dihydro-1H-2,13 Benzothiadiazine; 1,2,3,4-tetrahydrocinnoline, 1,2,3,4-tetrahydrophthalazine, 1,2,3,4-tetrahydroquinazoline, 1,2,3,4-tetrahydroquinoxaline Benzodiazine such as 3,4-dihydro-1,2-benzoxathiin, 3,4-dihydro-2,1-benzoxathiin, 2,3-dihydro-1,4-benzoxathiin, 1,4- Benzoxathines such as dihydro-2,3-benzoxathiin, 4H-1,3-benzoxathiin, 4H-3,1-benzoxathiin; 1,3-benzodioxole; 1,3-benzodithiol 3,4-dihydro-1,2-benzodioxin, 2,3-dihydro-1,4-benzodioxine, 1,4-dihydro-2,3-benzodioxin, 4H- Benzodioxins such as 1,3-benzodioxin; 3,4-dihydro-1,2-benzdithiin, 2,3-dihydro-1,4-benzdithiin, 1,4-dihydro-2,3-benzdithiine, 4H-1 Benzdithiin such as 2,3-benzdithiin; 2,3,4,5-tetrahydro-1,2-benzoxazepine, 2,3,4,5-tetrahydro-1,3-benzoxazepine, 2,3,4 4,5-tetrahydro-1,4-benzoxazepine, 2,3,4,5-tetrahydro-1,5-benzoxazepine, 1,3,4,5-tetrahydro-2,1-benzoxapine Zepin, 1,3,4,5-tetrahydro-2,3-benzoxazepine, 1,3,4,5-tetrahydro-2,4-benzoxazepine, 1,2,4,5-tetrahydro -3, 1-Be Benzoxazepines such as oxoxazepine, 1,2,4,5-tetrahydro-3,2-benzoxazepine, 1,2,3,5-tetrahydro-4,1-benzoxazepine; 4,5-tetrahydro-1,2-benzothiazepine, 2,3,4,5-tetrahydro-1,4-benzothiazepine, 2,3,4,5-tetrahydro-1,5-benzothiazepine, 1,3,4,5-tetrahydro-2,1-benzothiazepine, 1,3,4,5-tetrahydro-2,4-benzothiazepine, 1,2,4,5-tetrahydro-3,1- Benzothiazepines such as benzothiazepine, 1,2,4,5-tetrahydro-3,2-benzothiazepine, 1,2,3,5-tetrahydro-4,1-benzothiazepine; 2,3,4 , 5-Tetrahydro-1H-1,2 Benzothiazepine, 2,3,4,5-tetrahydro-1H-1,3-benzodiazepine, 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine, 2,3,4,5-tetrahydro- Benzodiazepines such as 1H-1,5-benzodiazepine, 2,3,4,5-tetrahydro-1H-2,3-benzodiazepine, 2,3,4,5-tetrahydro-1H-2,4-benzodiazepine; -Dihydro-1,3-benzodioxepin, 4,5-dihydro-3H-1,2-benzodioxepin, 2,3-dihydro-5H-1,4-benzodioxepin, 3,4- Benzodioxepines such as dihydro-2H-1,5-benzodioxepin, 4,5-dihydro-1H-2,3-benzodioxepin, 1,5-dihydro-2,4-benzodioxepin 4,5-dihydro-1H-2,3-benzothiepine, 1,5-dihydro-2,4-benzodithiepine, 3,4-dihydro-2H-1,5-benzodithiepine, 2,3-dihydro-5H- Benzodithiepine such as 1,4-benzodithiepine, 3,4,5,6-tetrahydro-2H-1,5-benzoxazocine, 3,4,5,6-tetrahydro-2H-1,6-benzoxazocine, etc. Benzoxazocine; benzothiazocine such as 3,4,5,6-tetrahydro-2H-1,5-benzothiazocine, 3,4,5,6-tetrahydro-2H-1,6-benzothiazocine; 1,2,3,4 Benzodiazocine such as 2,6,6-hexahydro-1,6-benzodiazocine; benzoxy such as 2,3,4,5-tetrahydro-1,6-benzoxiathiocin Thiocin; benzodioxocin such as 2,3,4,5-tetrahydro-1,6-benzodioxocin; 1,3,5-benzotrioxepin, 5H-1,3,4-benzotrioxepin Benzotrioxepin such as 3,4-dihydro-1H-5,2,1-benzoxathiazepine, 3,4-dihydro-2H-5,1,2-benzoxathiazepine, 4,5-dihydro Benzoxathiazepines such as 3,3,4-benzoxathiazepine and 4,5-dihydro-3H-1,2,5-benzoxathiazepine; 2,3,4,5-tetrahydro-1,3 Benzoxadiazepines such as 1,4-benzoxadiazepine; Benzthiazepines such as 2,3,4,5-tetrahydro-1,3,5-benzthiadiazepine; 2,3,4,5-tetrahydro -1H- Benzotriazepines such as 2,5-benzotriazepine; 4,5-dihydro-1,3,2-benzoxathiepine, 4,5-dihydro-1H-2,3-benzoxathiepine, 3, 4-dihydro-2H-1,5-benzoxathiepine, 4,5-dihydro-3H-1,2-benzoxathiepine, 4,5-dihydro-3H-2,1-benzoxathiepine, 2 , 3-dihydro-5H-1,4-benzoxathiepine, 2,3-dihydro-5H-4,1-benzoxathiepine, among others naphthalene, tetrahydronaphthalene, indane, indene, 2,3,4, 5-tetrahydro-1H-3-benzazepine, 2,3,4,5-tetrahydro-1H-2-benzazepine, 2,3-dihydro-1H-indole, 2,3,4,5-tetrahydro-1,4- Bicyclic condensed benzenes such as dexoxazepine, 2,3-dihydro-1-benzofuran, chroman, 1,3-dihydro-2H-benzimidazol-2-one, 1,3-dihydro-2,1,3-benzothiadiazole And a group formed by removing one hydrogen atom from the ring.

〔式中、Ｂ'環は置換基を有していてもよい５ないし９員の含窒素複素環、Ｂ”環は置換基を有していてもよい５ないし９員の含酸素複素環、その他の各記号は前記と同意義を示す。〕で表される基等が挙げられる。
該「置換基を有していてもよい５ないし９員の含窒素複素環」の「５ないし９員の含窒素複素環」としては、炭素原子及び１個の窒素原子以外に、例えば窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子を１ないし３個含有していてもよい５ないし９員の含窒素複素環等が挙げられ、５ないし９員の非芳香族含窒素複素環（例えば、ピロリジン、ピペリジン、ヘキサメチレンイミン、ヘプタメチレンイミン、ピペラジン、ホモピペラジン、テトラヒドロオキサゼピン、モルホリン、チオモルホリン、ヘキサヒドロピリミジン、イミダゾリジン、チアジアゾリジン等）等が好ましく用いられる。該「置換基」としては、上記Ｂ環で示される「置換基を有していてもよい同素環又は複素環」の「置換基」と同様のものから選ばれる１ないし３個の置換基が挙げられる。
該「置換基を有していてもよい５ないし９員の含酸素複素環」の「５ないし９員の含酸素複素環」としては、炭素原子及び１個の酸素原子以外に、例えば酸素原子及び硫黄原子から選ばれるヘテロ原子を１ないし３個含有していてもよい５ないし９員の含酸素複素環等が挙げられ、５ないし９員の非芳香族含酸素複素環（例えば、テトラヒドロフラン、テトラヒドロピラン、オキセパン等）等が好ましく用いられる。該「置換基」としては、上記のＢ環で示される「置換基を有していてもよい同素環又は複素環」の「置換基」と同様のものから選ばれる１ないし３個の置換基が挙げられるが、好ましくは、オキソ、Ｃ₁₋₆アルキル、Ｃ₁₋₆アルキル−カルボニルアミノ、Ｃ₁₋₆アルキルスルホニルアミノ等である。 Preferred examples when the ring B is a heterocyclic ring include the formula

[Wherein, the B ′ ring optionally has a 5- to 9-membered nitrogen-containing heterocycle, the B ″ ring optionally has a 5- to 9-membered oxygen-containing heterocycle, Other symbols are as defined above.] And the like.
The “5- to 9-membered nitrogen-containing heterocycle” of the “optionally substituted 5- to 9-membered nitrogen-containing heterocycle” includes, for example, a nitrogen atom in addition to a carbon atom and one nitrogen atom A 5- to 9-membered nitrogen-containing heterocycle optionally containing 1 to 3 heteroatoms selected from an oxygen atom and a sulfur atom, and the like. Pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, piperazine, homopiperazine, tetrahydrooxazepine, morpholine, thiomorpholine, hexahydropyrimidine, imidazolidine, thiadiazolidine and the like. The “substituent” is 1 to 3 substituents selected from the same “substituents” as the “homogeneous ring or heterocycle optionally having substituents” represented by ring B above. Is mentioned.
The “5- to 9-membered oxygen-containing heterocycle” of the “optionally substituted 5- to 9-membered oxygen-containing heterocycle” includes, for example, an oxygen atom in addition to a carbon atom and one oxygen atom. And 5- to 9-membered oxygen-containing heterocycles which may contain 1 to 3 heteroatoms selected from sulfur atoms, and the like, and 5- to 9-membered non-aromatic oxygen-containing heterocycles (for example, tetrahydrofuran, Tetrahydropyran, oxepane, etc.) are preferably used. The “substituent” is 1 to 3 substituents selected from the same “substituents” of the “homogeneous or heterocyclic ring optionally having substituent (s)” represented by ring B above. Examples of the group include oxo, C _1-6 alkyl, C _1-6 alkyl-carbonylamino, C _1-6 alkylsulfonylamino and the like.

で表される基のうち、より好ましい例としては、式

〔式中、Ｂａ環は置換基を有していてもよい同素環又は複素環を示し、Ｒ^1'はＲ¹と同意義を示し、その他の記号は前記と同意義を示す。〕で表される基等が挙げられる。 formula

As a more preferred example of the group represented by

[Wherein, the Ba ring represents an optionally substituted homocyclic ring or heterocyclic ring, R ^{1 ′} represents the same meaning as R ^1, and other symbols represent the same meaning as described above. The group etc. which are represented by these are mentioned.

As the “substituent” of the “homocyclic ring or heterocyclic ring optionally having substituent” represented by Ba ring, the “homocyclic ring optionally having substituent” represented by B ring above Or “substituent” of “heterocycle” includes 1 or 2 substituents selected from those similar to those other than the oxo group.
Here, the A ring has 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. The benzene ring which may be substituted, and the Ba ring may have one or two substituents each selected from C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. , R ¹ and R ^{1 ′} are each (1) a C _1-6 alkyl group which may have 1 or 2 substituents each selected from hydroxy and C _1-6 alkoxy-carbonyl, or C _7-16 Aralkyl group or (2) Formula — (C═O) —R ^{2 ′} , — (C═O) —NR ^{2 ′} R ^{3 ′} or —SO ₂ R ^{2 ′ wherein} R ^{2 ′} and R ^{3 ′} are Each hydrogen atom, halogenated Good C _1-6 alkyl or C _6-10 aryl is indicated. ] Is preferable.

〔式中、Ａ環は上記と同意義、Ｃ環及びＤ環は置換基を有していてもよい同素環又は複素環を示す。〕で表される基等が挙げられる。
Ｃ環又はＤ環で示される「置換基を有していてもよい同素環」の「同素環」としては、Ｂ環で示される「置換基を有していてもよい同素環」の「同素環」と同様のものが挙げられる。
Ｃ環又はＤ環で示される「置換基を有していてもよい複素環」の「複素環」としては、窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子を１ないし３個含有していてもよい５ないし９員複素環（例えば、ピリジン、ピラジン、ピリミジン、イミダゾール、フラン、チオフェン、ジヒドロピリジン、ジアゼピン、オキサゼピン、ピロリジン、ピペリジン、ヘキサメチレンイミン、ヘプタメチレンイミン、テトラヒドロフラン、ピペラジン、ホモピペラジン、テトラヒドロオキサゼピン、モルホリン、チオモルホリン、ヘキサヒドロピリミジン、イミダゾリジン、チアジアゾリジン等）等が挙げられる。
Ｃ環又はＤ環で示される「置換基を有していてもよい同素環又は複素環」の「置換基」としては、上記Ｂ環で示される「置換基を有していてもよい同素環又は複素環」の「置換基」と同様のものが挙げられる。 The bicyclic allocyclic ring in which the phenyl group in the above-mentioned (b) “which may be condensed and the phenyl group may have a substituent” may have a substituent or Specific examples of the case where it is condensed with a heterocyclic ring or condensed with two identical or different monocyclic homocyclic or heterocyclic rings include, for example, the formula

[Wherein, A ring represents the same meaning as described above, and C ring and D ring represent a homocyclic ring or a heterocyclic ring which may have a substituent. The group etc. which are represented by these are mentioned.
As the “homocyclic ring” of the “homocyclic ring optionally having substituents” represented by C ring or D ring, “homocyclic ring optionally having substituents” represented by B ring The same as the “homocyclic ring” of
The “heterocycle” of the “optionally substituted heterocycle” represented by C ring or D ring contains 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom. 5- to 9-membered heterocyclic ring (for example, pyridine, pyrazine, pyrimidine, imidazole, furan, thiophene, dihydropyridine, diazepine, oxazepine, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, tetrahydrofuran, piperazine, homopiperazine, tetrahydro Oxazepine, morpholine, thiomorpholine, hexahydropyrimidine, imidazolidine, thiadiazolidine, and the like.
The “substituent” of the “homocyclic ring or heterocyclic ring optionally having substituent” represented by C ring or D ring is the same as the “optionally substituted substituent” represented by ring B above. Examples thereof are the same as the “substituent” of “primary ring or heterocyclic ring”.

〔式中、各記号は上記と同意義を示す。〕で表される基の具体例としては、アントラセン、カルバゾール、１，２，３，４，４ａ，９ａ−ヘキサヒドロカルバゾール、９，１０−ジヒドロアクリジン、１，２，３，４−テトラヒドロアクリジン、１０，１１−ジヒドロ−５Ｈ−ジベンズ〔ｂ，ｆ〕アゼピン、５，６，７，１２−テトラヒドロジベンズ〔ｂ，ｇ〕アゾシン、６，１１−ジヒドロ−５Ｈ−ジベンズ〔ｂ，ｅ〕アゼピン、６，７−ジヒドロ−５Ｈ−ジベンズ〔ｃ，ｅ〕アゼピン、５，６，１１，１２−テトラヒドロジベンズ〔ｂ，ｆ〕アゾシン、ジベンゾフラン、９Ｈ−キサンテン、１０，１１−ジヒドロジベンズ〔ｂ，ｆ〕オキセピン、６，１１−ジヒドロジベンズ〔ｂ，ｅ〕オキセピン、６，７−ジヒドロ−５Ｈ−ジベンズ〔ｂ，ｇ〕オキソシン、ジベンゾチオフェン、９Ｈ−チオキサンテン、１０，１１−ジヒドロジベンゾ〔ｂ，ｆ〕チエピン、６，１１−ジヒドロジベンゾ〔ｂ，ｅ〕チエピン、６，７−ジヒドロ−５Ｈ−ジベンゾ〔ｂ，ｇ〕チオシン、１０Ｈ−フェノチアジン、１０Ｈ−フェノキサジン、５，１０−ジヒドロフェナジン、１０，１１−ジベンゾ〔ｂ，ｆ〕〔１，４〕チアゼピン、１０，１１−ジヒドロジベンズ〔ｂ，ｆ〕〔１，４〕オキサゼピン、２，３，５，６，１１，１１ａ−ヘキサヒドロ−１Ｈ−ピロロ〔２，１−ｂ〕〔３〕ベンズアゼピン、１０，１１−ジヒドロ−５Ｈ−ジベンゾ〔ｂ，ｅ〕〔１，４〕ジアゼピン、５，１１−ジヒドロジベンズ〔ｂ，ｅ〕〔１，４〕オキサゼピン、５，１１−ジヒドロジベンゾ〔ｂ，ｆ〕〔１，４〕チアゼピン、１０，１１−ジヒドロ−５Ｈ−ジベンゾ〔ｂ，ｅ〕〔１，４〕ジアゼピン、１，２，３，３ａ，８，８ａ−ヘキサヒドロピロロ〔２，３−ｂ〕インドール等の３環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. Specific examples of the group represented by the formula: anthracene, carbazole, 1,2,3,4,4a, 9a-hexahydrocarbazole, 9,10-dihydroacridine, 1,2,3,4-tetrahydroacridine, 10,11-dihydro-5H-dibenz [b, f] azepine, 5,6,7,12-tetrahydrodibenz [b, g] azocine, 6,11-dihydro-5H-dibenz [b, e] azepine, 6,7-dihydro-5H-dibenz [c, e] azepine, 5,6,11,12-tetrahydrodibenz [b, f] azocine, dibenzofuran, 9H-xanthene, 10,11-dihydrodibenz [b, f] oxepin, 6,11-dihydrodibenz [b, e] oxepin, 6,7-dihydro-5H-dibenz [b, g] oxocine, dibenzothiophene 9H-thioxanthene, 10,11-dihydrodibenzo [b, f] thiepine, 6,11-dihydrodibenzo [b, e] thiepine, 6,7-dihydro-5H-dibenzo [b, g] thiocin, 10H- Phenothiazine, 10H-phenoxazine, 5,10-dihydrophenazine, 10,11-dibenzo [b, f] [1,4] thiazepine, 10,11-dihydrodibenz [b, f] [1,4] oxazepine, 2,3,5,6,11,11a-hexahydro-1H-pyrrolo [2,1-b] [3] benzazepine, 10,11-dihydro-5H-dibenzo [b, e] [1,4] diazepine, 5,11-dihydrodibenz [b, e] [1,4] oxazepine, 5,11-dihydrodibenzo [b, f] [1,4] thiazepine, 10,11-dihydro-5 1 hydrogen atom from a tricyclic fused benzene ring such as dibenzo [b, e] [1,4] diazepine, 1,2,3,3a, 8,8a-hexahydropyrrolo [2,3-b] indole Examples include groups formed by removing the individual.

〔式中、各記号は上記と同意義を示す。〕で表される基の具体例としては、フェナレン、アセナフチレン、１Ｈ，３Ｈ−ナフト〔１，８−ｃｄ〕〔１，２〕オキサジン、ナフト〔１，８−ｄｅ〕−１，３−オキサジン、ナフト〔１，８−ｄｅ〕−１，２−オキサジン、１，２，２ａ，３，４，５−ヘキサヒドロベンズ〔ｃｄ〕インドール、２，３，３ａ，４，５，６−ヘキサヒドロ−１Ｈ−ベンゾ〔ｄｅ〕キノリン、４Ｈ−ピロロ〔３，２，１−ｉｊ〕キノリン、１，２，５，６−テトラヒドロ−４Ｈ−ピロロ〔３，２，１−ｉｊ〕キノリン、５，６−ジヒドロ−４Ｈ−ピロロ〔３，２，１−ｉｊ〕キノリン、１Ｈ−ピロロ〔３，２，１−ｉｊ〕キナゾリン、４Ｈ−イミダゾ〔４，５，１−ｉｊ〕キノリン、２，３，７，８−テトラヒドロ〔１，２，６〕チアジアジノ〔４，３，２−ｈｉ〕インドール、1,2,6,7-テトラヒドロ-3H,5H-ピリド[3,2,1-ij]キナゾリン、2,3,8,9-テトラヒドロ-7H-[1,2,6]チアジアジノ[4,3,2-ij]キノリン５，６−ジヒドロ−１Ｈ，４Ｈ−〔１，２，５〕チアジアゾロ〔４，３，２−ｉｊ〕キノリン、１Ｈ，５Ｈ−ベンゾ〔ｉｊ〕キノリジン、アゼピノ〔３，２，１−ｈｉ〕インドール、１，２，４，５，６，７−ヘキサヒドロアゼピノ〔３，２，１−ｈｉ〕インドール、１Ｈ−ピリド〔３，２，１−ｊｋ〕〔１〕ベンズアゼピン、５，６，７，８−テトラヒドロ−１Ｈ−ピリド〔３，２，１−ｊｋ〕〔１〕ベンズアゼピン、１，２，５，６，７，８−ヘキサヒドロ−１Ｈ−ピリド〔３，２，１−ｊｋ〕〔１〕ベンズアゼピン、２，３−ジヒドロ−１Ｈ−ベンズ〔ｄｅ〕イソキノリン、１，２，３，４，４ａ，５，６，７−オクタヒドロナフト〔１，８−ｂｃ〕アゼピン、２，３，５，６，７，８−ヘキサヒドロ−１Ｈ−ピリド〔３，２，１−ｊｋ〕〔１〕ベンズアゼピン等の３環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. Specific examples of the group represented by the formula: phenalene, acenaphthylene, 1H, 3H-naphtho [1,8-cd] [1,2] oxazine, naphtho [1,8-de] -1,3-oxazine, Naphtho [1,8-de] -1,2-oxazine, 1,2,2a, 3,4,5-hexahydrobenz [cd] indole, 2,3,3a, 4,5,6-hexahydro-1H -Benzo [de] quinoline, 4H-pyrrolo [3,2,1-ij] quinoline, 1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline, 5,6-dihydro -4H-pyrrolo [3,2,1-ij] quinoline, 1H-pyrrolo [3,2,1-ij] quinazoline, 4H-imidazo [4,5,1-ij] quinoline, 2,3,7,8 -Tetrahydro [1,2,6] thiadiazino [4,3,2 hi] indole, 1,2,6,7-tetrahydro-3H, 5H-pyrido [3,2,1-ij] quinazoline, 2,3,8,9-tetrahydro-7H- [1,2,6] thiadiazino [4,3,2-ij] quinoline 5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinoline, 1H, 5H-benzo [ij] quinolidine, azepino [3,2,1-hi] indole, 1,2,4,5,6,7-hexahydroazepino [3,2,1-hi] indole, 1H-pyrido [3,2,1-jk] [1] Benzazepine, 5,6,7,8-tetrahydro-1H-pyrido [3,2,1-jk] [1] Benzazepine, 1,2,5,6,7,8-hexahydro-1H-pyrido [ 3,2,1-jk] [1] benzazepine, 2,3-dihydro-1H-benz [de] isoquinoline, 1,2,3,4,4a, 5 , 7-octahydronaphtho [1,8-bc] azepine, 2,3,5,6,7,8-hexahydro-1H-pyrido [3,2,1-jk] [1] benzazepine And a group formed by removing one hydrogen atom from the condensed benzene ring.

〔式中、各記号は上記と同意義を示す。〕で表される基の具体例としては、アントラセン、１，２，３，５，６，７−ヘキサヒドロベンゾ〔１，２−ｂ：４，５−ｂ'〕ジピロール、１，２，３，５，６，７−ヘキサヒドロシクロペント〔ｆ〕インドール等の３環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. Specific examples of the group represented by anthracene, 1,2,3,5,6,7-hexahydrobenzo [1,2-b: 4,5-b ′] dipyrrole, 1,2,3 And a group formed by removing one hydrogen atom from a tricyclic fused benzene ring such as, 5,6,7-hexahydrocyclopent [f] indole.

〔式中、各記号は上記と同意義を示す。〕で表される基の具体例としては、フェナントロレン、１，２，３，６，７，８−ヘキサヒドロシクロペント〔ｅ〕インドール、２，３，４，７，８，９−ヘキサヒドロ−１Ｈ−シクロペンタ〔ｆ〕キノリン等の３環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. Specific examples of the group represented by phenanthrolene, 1,2,3,6,7,8-hexahydrocyclopent [e] indole, 2,3,4,7,8,9-hexahydro And a group formed by removing one hydrogen atom from a tricyclic fused benzene ring such as -1H-cyclopenta [f] quinoline.

〔式中、Ｃ'環及びＤ'環は、それぞれ置換基を有していてもよい５ないし９員の含窒素複素環、その他の各記号は前記と同意義を示す。〕で表される基等が好ましい。このうち式

〔式中、各記号は前記と同意義を示す。〕で表される基等が更に好ましい。
Ｃ'環又はＤ'環で示される「置換基を有していてもよい５ないし９員の含窒素複素環」は、Ｂ'環で示される「置換基を有していてもよい５ないし９員の含窒素複素環」と同様のものが挙げられる。該置換基としてはオキソ基が好ましい。 Of these, the formula

[Wherein, the C ′ ring and the D ′ ring each have a 5- to 9-membered nitrogen-containing heterocyclic ring which may have a substituent, and other symbols are as defined above. And the like are preferred. Of these expressions

[Wherein each symbol is as defined above. And the like are more preferred.
The “optionally substituted 5- to 9-membered nitrogen-containing heterocycle” represented by the C ′ ring or the D ′ ring is the “optionally substituted 5 to 9” represented by the B ′ ring. Examples thereof include those similar to “9-membered nitrogen-containing heterocycle”. The substituent is preferably an oxo group.

〔式中、Ｃ”環及びＤ”環はそれぞれ置換基を有していてもよい含窒素複素環を示し、その他の記号は前記と同意義を示す。〕で表される基が挙げられる。
Ｃ”環及びＤ”環で示される「置換基を有していてもよい含窒素複素環」の「置換基」としては、上記のＢ環で示される「置換基を有していてもよい同素環又は複素環」の「置換基」のうちオキソ基以外のものと同様のものから選ばれる１または２個の置換基が挙げられる。
ここで、Ａ環がアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、カルバモイルおよびモノ−又はジ−Ｃ₁₋₆アルキル−カルバモイルから選ばれる１または２個の置換基を有していてもよいベンゼン環で、Ｃ”環及びＤ”環がそれぞれＣ₁₋₆アルキル、Ｃ₁₋₆アルキル−カルボニルアミノ及びＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有していてもよく、Ｒ^１が（1）それぞれヒドロキシおよびＣ₁₋₆アルコキシ−カルボニルから選ばれる１または２個の置換基を有していてもよいＣ₁₋₆アルキル基またはＣ₇₋₁₆アラルキル基または（2）式−(Ｃ＝Ｏ)−Ｒ^２'、 −(Ｃ＝Ｏ)−ＮＲ^２'Ｒ^３'または−ＳＯ_２Ｒ^２'〔式中、Ｒ^２'及びＲ^３'はそれぞれ水素原子、ハロゲン化されていてもよいＣ₁₋₆アルキルまたはＣ₆₋₁₀アリールを示す。〕であるものが好ましい。 More preferably, the formula

[Wherein, the C ″ ring and the D ″ ring each represent a nitrogen-containing heterocyclic ring which may have a substituent, and other symbols have the same meaning as described above. The group represented by this is mentioned.
The “substituent” of the “optionally substituted nitrogen-containing heterocycle” represented by the C ″ ring and the D ″ ring may have the “substituent” represented by the B ring above. Among the “substituents” of the “homocyclic or heterocyclic ring”, 1 or 2 substituents selected from those similar to those other than the oxo group can be mentioned.
Here, the A ring has 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. In which the C ″ ring and the D ″ ring each have one or two substituents selected from C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. R ¹ may be (1) a C _1-6 alkyl group optionally having 1 or 2 substituents each selected from hydroxy and C _1-6 alkoxy-carbonyl, or C _7-16. Aralkyl group or (2) Formula — (C═O) —R ^{2 ′} , — (C═O) —NR ^{2 ′} R ^{3 ′} or —SO ₂ R ^{2 ′ wherein} R ^{2 ′} and R ^{3 ′} are Hydrogen atom, optionally halogenated C _{1 -6} alkyl or _C6-10 aryl is shown. ] Is preferable.

〔式中、Ａ環は上記と同意義、Ｅ環、Ｆ環及びＧ環は置換基を有していてもよい同素環又は複素環を示す。〕で表される基等が挙げられる。
Ｅ環、Ｆ環又はＧ環で示される「置換基を有していてもよい同素環又は複素環」は、Ｃ環又はＤ環で示される「置換基を有していてもよい同素環又は複素環」と同様のものが挙げられる。
このうち、好ましくは
（i）式

〔式中、Ｅ'環、Ｆ'環及びＧ'環はそれぞれ置換基を有していてもよい５ないし９員の含窒素複素環を、 - - -は単結合又は二重結合を、その他の記号は前記と同意義を示す。〕で表される基、
（ii）例えば、フルオランテン、アセフェナントリレン、アセアントリレン、トリフェニレン、ピレン、クリセン、ナフタセン、プレイアデン、ベンゾ［ａ］アントラセン、インデノ［１，２−ａ］インデン、シクロペンタ［ａ］フェナントレン、ピリド［１’，２’：１，２］イミダゾ［４，５−ｂ］キノキサリン、１Ｈ−２−オキサピレン、スピロ［ピペリジン−４．９’−キサンテン］等の環から水素原子を１個除去してできる基、及びこれらのジヒドロ体、テトラヒドロ体、ヘキサヒドロ体、オクタヒドロ体、デカヒドロ体等が挙げられる。
Ｅ'環、Ｆ'環及びＧ'環で示される「置換基を有していてもよい５ないし９員の含窒素複素環」は、Ｂ'環で示される「置換基を有していてもよい５ないし９員の含窒素複素環」と同様のものが挙げられる。該置換基としてはオキソ基が好ましい。 The tricyclic allocyclic ring in which the phenyl group in (c) “which may be condensed with the phenyl group may have a substituent” may have a substituent, Specific examples of the case of condensing with a heterocyclic ring include, for example, the formula

[Wherein, A ring has the same meaning as described above, and E ring, F ring and G ring each represent an allocyclic ring or heterocyclic ring which may have a substituent. The group etc. which are represented by these are mentioned.
The “homocyclic ring or heterocyclic ring optionally having substituent (s)” represented by the E ring, F ring or G ring is the same allotrope optionally having substituent (s) represented by the C ring or D ring. The same thing as "a ring or a heterocyclic ring" is mentioned.
Of these, preferably the formula (i)

[Wherein, the E ′ ring, the F ′ ring and the G ′ ring each represent a 5- to 9-membered nitrogen-containing heterocyclic ring which may have a substituent, − − − represents a single bond or a double bond, and others The symbol represents the same meaning as described above. A group represented by
(Ii) For example, fluoranthene, acephenanthrylene, acanthrylene, triphenylene, pyrene, chrysene, naphthacene, pleiaden, benzo [a] anthracene, indeno [1,2-a] indene, cyclopenta [a] phenanthrene, pyrido One hydrogen atom is removed from a ring such as [1 ′, 2 ′: 1,2] imidazo [4,5-b] quinoxaline, 1H-2-oxapyrene, spiro [piperidine-4.9′-xanthene], etc. And a dihydro form, tetrahydro form, hexahydro form, octahydro form, decahydro form and the like thereof.
The “optionally substituted 5- to 9-membered nitrogen-containing heterocycle” represented by the E ′ ring, the F ′ ring and the G ′ ring is the “substituted group” represented by the B ′ ring. And the same as “a 5- to 9-membered nitrogen-containing heterocycle”. The substituent is preferably an oxo group.

〔式中、各記号は前記と同意義を示す。〕で表される基の具体例としては、２Ｈ−イソインドロ〔２,１−e〕プリン，１Ｈ−ピラゾロ〔４'，３'：３，４〕ピリド〔２,１−a〕イソインドール，１Ｈ−ピリド〔２'，３'：４，５〕イミダゾ〔２,１−a〕イソインドール，２Ｈ，６Ｈ−ピリド〔１'，２'：３，４〕イミダゾ〔５,１−a〕イソインドール，１Ｈ−イソインドロ〔２,１−a〕ベンズイミダゾール，１Ｈ−ピリド〔３'，４'：４，５〕ピロロ〔２,１−a〕イソインドール，２Ｈ−ピリド〔４'，３'：４，５〕ピロロ〔２,１−a〕イソインドール，１Ｈ−イソインドロ〔２,１−a〕インドール，２Ｈ−イソインドロ〔１,２−a〕イソインドール，１Ｈ−シクロペンタ〔４，５〕ピリミド〔２,１−a〕イソインドール，２Ｈ，４Ｈ−ピラノ〔４'，３'：４，５〕〔１,３〕オキサジノ〔２,３−a〕イソインドール，２Ｈ−イソインドロ〔２,１−a〕〔３,１〕ベンズオキサジン，７Ｈ−イソインドロ〔１,２−b〕〔１,３〕ベンズオキサジン，２Ｈ−ピリド〔２'，１'：３，４〕ピラジノ〔２,１−a〕イソインドール，ピリド〔２'，３'：４，５〕ピリミド〔２,１−a〕イソインドール，ピリド〔３'，２'：５，６〕ピリミド〔２,１−a〕イソインドール，１Ｈ−ピリド〔１'，２'：３，４〕ピリミド〔２,１−a〕イソインドール，イソインドロ〔２,１−a〕キナゾリン，イソインドロ〔２,１−a〕キノキサリン，イソインドロ〔１,２−a〕イソキノリン，イソインドロ〔２,１−b〕イソキノリン，イソインドロ〔２,１−a〕キノリン，６Ｈ−オキサジノ〔３'，４'：３，４〕〔１,４〕ジアゼピノ〔２,１−a〕イソインドール，アゼピノ〔２'，１'：３，４〕ピラジノ〔２,１−a〕イソインドール，２Ｈ，６Ｈ−ピリド〔２'，１'：３，４〕〔１,４〕ジアゼピノ〔２,１−a〕イソインドール，１Ｈ−イソインドロ〔１,２−b〕〔１,３,４〕ベンゾトリアゼピン，２Ｈ−イソインドロ〔２,１−a〕〔１,３,４〕ベンゾトリアゼピン，イソインドロ〔２,１−d〕〔１,４〕ベンズオキサゼピン，１Ｈ−イソインドロ〔２,１−b〕〔２,４〕ベンゾジアゼピン，１Ｈ−イソインドロ〔２,１−c〕〔２,３〕ベンゾジアゼピン，２Ｈ−イソインドロ〔１,２−a〕〔２,４〕ベンゾジアゼピン，２Ｈ−イソインドロ〔２,１−d〕〔１,４〕ベンゾジアゼピン，５Ｈ−インドロ〔２,１−b〕〔３〕ベンズアゼピン，２Ｈ−イソインドロ〔１,２−a〕〔２〕ベンズアゼピン，２Ｈ−イソインドロ〔１,２−b〕〔３〕ベンズアゼピン，２Ｈ−イソインドロ〔２,１−b〕〔２〕ベンズアゼピン，２Ｈ−イソインドロ〔１,２−b〕〔１,３,４〕ベンゾオキサジアゾシン，イソインドロ〔２,１−b〕〔１,２,６〕ベンゾトリアゾシン，５Ｈ−４,８−メタノ−１Ｈ−〔１,５〕ジアザシクロウンデシノ〔１,１１−a〕インドール等の４環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. Specific examples of the group represented by the formula: 2H-isoindolo [2,1-e] purine, 1H-pyrazolo [4 ′, 3 ′: 3,4] pyrido [2,1-a] isoindole, 1H -Pyrido [2 ', 3': 4,5] imidazo [2,1-a] isoindole, 2H, 6H-pyrido [1 ', 2': 3,4] imidazo [5,1-a] isoindole , 1H-isoindolo [2,1-a] benzimidazole, 1H-pyrido [3 ′, 4 ′: 4,5] pyrrolo [2,1-a] isoindole, 2H-pyrido [4 ′, 3 ′: 4 , 5] pyrrolo [2,1-a] isoindole, 1H-isoindolo [2,1-a] indole, 2H-isoindolo [1,2-a] isoindole, 1H-cyclopenta [4,5] pyrimido [2 , 1-a] isoindole, 2H, 4H-pyrano [4 ′, 3 ′: 4,5] [1,3] oxazino [2,3 -A] isoindole, 2H-isoindolo [2,1-a] [3,1] benzoxazine, 7H-isoindolo [1,2-b] [1,3] benzoxazine, 2H-pyrido [2 ', 1 ': 3,4) pyrazino [2,1-a] isoindole, pyrido [2', 3 ': 4,5] pyrimido [2,1-a] isoindole, pyrido [3', 2 ': 5 6] pyrimido [2,1-a] isoindole, 1H-pyrido [1 ′, 2 ′: 3,4] pyrimido [2,1-a] isoindole, isoindolo [2,1-a] quinazoline, isoindolo [ 2,1-a] quinoxaline, isoindolo [1,2-a] isoquinoline, isoindolo [2,1-b] isoquinoline, isoindolo [2,1-a] quinoline, 6H-oxazino [3 ', 4': 3 4] [1,4] diazepino [2,1-a] isoindole, azepino [2 ′, 1 ′ : 3,4] pyrazino [2,1-a] isoindole, 2H, 6H-pyrido [2 ', 1': 3,4] [1,4] diazepino [2,1-a] isoindole, 1H- Isoindolo [1,2-b] [1,3,4] benzotriazepine, 2H-isoindolo [2,1-a] [1,3,4] benzotriazepine, isoindolo [2,1-d] [1 , 4] benzoxazepine, 1H-isoindolo [2,1-b] [2,4] benzodiazepine, 1H-isoindolo [2,1-c] [2,3] benzodiazepine, 2H-isoindolo [1,2- a] [2,4] benzodiazepine, 2H-isoindolo [2,1-d] [1,4] benzodiazepine, 5H-indolo [2,1-b] [3] benzazepine, 2H-isoindolo [1,2-a ] [2] Benzazepine, 2H-isoindolo [1,2-b] [3] Benz Zepin, 2H-isoindolo [2,1-b] [2] benzazepine, 2H-isoindolo [1,2-b] [1,3,4] benzooxadiazocine, isoindolo [2,1-b] [1, One hydrogen atom from a tetracyclic fused benzene ring such as 2,6] benzotriazocine, 5H-4,8-methano-1H- [1,5] diazacycloundecino [1,11-a] indole A group formed by removal can be mentioned.

〔式中、各記号は前記と同意義を示す。〕で表される基の具体例としては、１Ｈ，４Ｈ−ピロロ〔３'，２'：４,５〕ピロロ〔３,２,１−ij〕キノリン，ピロロ〔３,２,１−jk〕カルバゾール，１Ｈ−フロ〔２'，３'：４,５〕ピロロ〔３,２,１−ij〕キノリン，１Ｈ，４Ｈ−シクロペンタ〔４,５〕ピロロ〔１,２,３−de〕キノキサリン，１Ｈ，４Ｈ−シクロペンタ〔４,５〕ピロロ〔３,２,１−ij〕キノリン，ピリド〔３'，４'：４,５〕ピロロ〔１,２,３−de〕ベンズオキサジン，〔１,４〕オキサジノ〔２,３,４−jk〕カルバゾール，１Ｈ，３Ｈ−〔１,３〕オキサジノ〔５,４,３−jk〕カルバゾール，ピリド〔３'，４'：４,５〕ピロロ〔１,２,３−de〕〔１,４〕ベンゾチアジン，４Ｈ−ピロロ〔３,２,１−de〕フェナンスリジン，４Ｈ，５Ｈ−ピリド〔３,２,１−de〕フェナンスリジン，１Ｈ，４Ｈ−３a，６a−ジアザフルオロアンテン，１−オキサ−４,６a−ジアザフルオロアンテン，４−オキサ−２，１０b−ジアザフルオロアンテン，１−チア−４，６a−ジアザフルオロアンテン，１Ｈ−ピラジノ〔３,２,１−jk〕カルバゾール，１Ｈ−インドロ〔３,２,１−de〕〔１,５〕ナフチリジン，ベンゾ〔b〕ピラノ〔２,３,４−hi〕インドリジン，１Ｈ，３Ｈ−ベンゾ〔b〕ピラノ〔３,４,５−hi〕インドリジン，１Ｈ，４Ｈ−ピラノ〔２'，３'：４,５〕ピロロ〔３,２,１−ij〕キノリン，１Ｈ，３Ｈ−ベンゾ〔b〕チオピラノ〔３,４,５−hi〕インドリジン，１Ｈ−ピリド〔３,２,１−jk〕カルバゾール，４Ｈ−３−オキサ−１１b−アザシクロヘプタ〔jk〕フルオレン，２Ｈ−アゼピノ〔１'，２'：１,２〕ピリミジノ〔４,５−b〕インドール，１Ｈ，４Ｈ−シクロヘプタ〔４,５〕ピロロ〔１,２,３−de〕キノキサリン，５Ｈ−ピリド〔３'，４'：４,５〕ピロロ〔１,２,３−ef〕〔１,５〕ベンズオキサゼピン，４Ｈ−ピリド〔３'，４'：４,５〕ピロロ〔３,２,１−jk〕〔４,１〕ベンゾチアゼピン，５Ｈ−ピリド〔３'，４'：４,５〕ピロロ〔１,２,３−ef〕〔１,５〕ベンゾチアゼピン，５Ｈ−ピリド〔４'，３'：４,５〕ピロロ〔１,２,３−ef〕〔１,５〕ベンゾチアゼピン，〔１,２,４〕トリアゼピノ〔６,５,４−jk〕カルバゾール，〔１,２,４〕トリアゼピノ〔６,７,１−jk〕カルバゾール，〔１,２,５〕トリアゼピノ〔３,４,５−jk〕カルバゾール，５Ｈ−〔１,４〕オキサゼピノ〔２,３,４−jk〕カルバゾール，５Ｈ−〔１,４〕チアゼピノ〔２,３,４−jk〕カルバゾール，〔１,４〕ジアゼピノ〔３,２,１−jk〕カルバゾール，〔１,４〕ジアゼピノ〔６,７,１−jk〕カルバゾール，アゼピノ〔３,２,１−jk〕カルバゾール，１Ｈ−シクロオクタ〔４,５〕ピロロ〔１,２,３−de〕キノキサリン，１Ｈ−シクロオクタ〔４,５〕ピロロ〔３,２,１−ij〕キノリン等の４環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. ] As specific examples of the group represented by 1H, 4H-pyrrolo [3 ', 2': 4,5] pyrrolo [3,2,1-ij] quinoline, pyrrolo [3,2,1-jk] Carbazole, 1H-furo [2 ′, 3 ′: 4,5] pyrrolo [3,2,1-ij] quinoline, 1H, 4H-cyclopenta [4,5] pyrrolo [1,2,3-de] quinoxaline, 1H, 4H-cyclopenta [4,5] pyrrolo [3,2,1-ij] quinoline, pyrido [3 ′, 4 ′: 4,5] pyrrolo [1,2,3-de] benzoxazine, [1, 4] Oxazino [2,3,4-jk] carbazole, 1H, 3H- [1,3] oxazino [5,4,3-jk] carbazole, pyrido [3 ′, 4 ′: 4,5] pyrrolo [1 , 2,3-de] [1,4] benzothiazine, 4H-pyrrolo [3,2,1-de] phenanthridine, 4H, 5H-pyrido [3,2,1-de] phenanthridine, 1H, 4H -3a, 6a-diazafluoroanthene, 1-oxa-4,6a-diazafluoroanthene, 4-oxa-2,10b-diazafluoroanthene, 1-thia-4,6a-diazafluoroanthene, 1H -Pyrazino [3,2,1-jk] carbazole, 1H-indolo [3,2,1-de] [1,5] naphthyridine, benzo [b] pyrano [2,3,4-hi] indolizine, 1H , 3H-benzo [b] pyrano [3,4,5-hi] indolizine, 1H, 4H-pyrano [2 ′, 3 ′: 4,5] pyrrolo [3,2,1-ij] quinoline, 1H, 3H-benzo [b] thiopyrano [3,4,5-hi] indolizine, 1H-pyrido [3,2,1-jk] carbazole, 4H-3-oxa-11b-azacyclohepta [jk] fluorene, 2H-azepino [1 ', 2': 1,2] pyrimidino [4,5-b] indole, 1H, 4H Cyclohepta [4,5] pyrrolo [1,2,3-de] quinoxaline, 5H-pyrido [3 ′, 4 ′: 4,5] pyrrolo [1,2,3-ef] [1,5] benzoxa Zepin, 4H-pyrido [3 ′, 4 ′: 4,5] pyrrolo [3,2,1-jk] [4,1] benzothiazepine, 5H-pyrido [3 ′, 4 ′: 4,5] Pyrrolo [1,2,3-ef] [1,5] benzothiazepine, 5H-pyrido [4 ′, 3 ′: 4,5] pyrrolo [1,2,3-ef] [1,5] benzoti Azepine, [1,2,4] triazepino [6,5,4-jk] carbazole, [1,2,4] triazepino [6,7,1-jk] carbazole, [1,2,5] triazepino [3 , 4,5-jk] carbazole, 5H- [1,4] oxazepino [2,3,4-jk] carbazole, 5H- [1,4] thiazepino [2,3,4-jk] carbazole, [1, 4] Diazepino [3, 2, 1-jk] Carbazole, [1,4] diazepino [6,7,1-jk] carbazole, azepino [3,2,1-jk] carbazole, 1H-cycloocta [4,5] pyrrolo [1,2,3-de] quinoxaline , 1H-cycloocta [4,5] pyrrolo [3,2,1-ij] quinoline and the like, and a group formed by removing one hydrogen atom from a tetracyclic fused benzene ring.

〔式中、各記号は前記と同意義を示す。〕で表される基の具体例としては、１Ｈ−インドロ〔１,２−a〕ベンズイミダゾール，１Ｈ−インドロ〔１,２−b〕インダゾール，ピロロ〔２'，１'：３,４〕ピラジノ〔１,２−a〕インドール，１Ｈ，５Ｈ−ピロロ〔１'，２'：４,５〕ピラジノ〔１,２−a〕インドール，２Ｈ−ピリド〔２'，３'：３,４〕ピロロ〔１,２−a〕インドール，１Ｈ−ピロロ〔２'，３'：３,４〕ピリド〔１,２−a〕インドール，１Ｈ−インドロ〔１,２−a〕インドール，６Ｈ−イソインドロ〔２,１−a〕インドール，６Ｈ−インドロ〔１,２−c〕〔１,３〕ベンズオキサジン，１Ｈ−インドロ〔１,２−b〕〔１,２〕ベンゾチアジン，ピリミド〔４'，５'：４,５〕ピリミド〔１,６−a〕インドール，ピラジノ〔２'，３'：３,４〕ピリド〔１,２−a〕インドール，６Ｈ−ピリド〔１'，２'：３,４〕ピリミド〔１,６−a〕インドール，インドロ〔１,２−b〕シンノリン，インドロ〔１,２−a〕キナゾリン，インドロ〔１,２−c〕キナゾリン，インドロ〔２,１−b〕キナゾリン，インドロ〔１,２−a〕キノキサリン，インドロ〔１,２−a〕〔１,８〕ナフチリジン，インドロ〔１,２−b〕−２,６−ナフチリジン，インドロ〔１,２−b〕〔２,７〕ナフチリジン，インドロ〔１,２−h〕−１,７−ナフチリジン，インドロ〔１,２−b〕イソキノリン，インドロ〔２,１−a〕イソキノリン，インドロ〔１,２−a〕キノリン，２Ｈ，６Ｈ−ピリド〔２'，１'：３,４〕〔１,４〕ジアゼピノ〔１,２−a〕インドール，１Ｈ−インドロ〔２,１−c〕〔１,４〕ベンゾジアゼピン，２Ｈ−インドロ〔１,２−d〕〔１,４〕ベンゾジアゼピン，２Ｈ−インドロ〔２,１−a〕〔２,３〕ベンゾジアゼピン，２Ｈ−インドロ〔２,１−b〕〔１,３〕ベンゾジアゼピン，１Ｈ−インドロ〔１,２−b〕〔２〕ベンズアゼピン，２Ｈ−インドロ〔１,２−a〕〔１〕ベンズアゼピン，２Ｈ−インドロ〔２,１−a〕〔２〕ベンズアゼピン，インドロ〔１,２−e〕〔１,５〕ベンゾジアゾシン，インドロ〔２,１−b〕〔３〕ベンズアゾシン等の４環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. As specific examples of the group represented by the formula: 1H-indolo [1,2-a] benzimidazole, 1H-indolo [1,2-b] indazole, pyrrolo [2 ′, 1 ′: 3,4] pyrazino [1,2-a] indole, 1H, 5H-pyrrolo [1 ′, 2 ′: 4,5] pyrazino [1,2-a] indole, 2H-pyrido [2 ′, 3 ′: 3,4] pyrrolo [1,2-a] indole, 1H-pyrrolo [2 ′, 3 ′: 3,4] pyrido [1,2-a] indole, 1H-indolo [1,2-a] indole, 6H-isoindolo [2 , 1-a] indole, 6H-indolo [1,2-c] [1,3] benzoxazine, 1H-indolo [1,2-b] [1,2] benzothiazine, pyrimido [4 ', 5': 4,5] pyrimido [1,6-a] indole, pyrazino [2 ', 3': 3,4] pyrido [1,2-a] indole, 6H-pyrido [ ', 2': 3,4] pyrimido [1,6-a] indole, indolo [1,2-b] cinnoline, indolo [1,2-a] quinazoline, indolo [1,2-c] quinazoline, indolo [2,1-b] quinazoline, indolo [1,2-a] quinoxaline, indolo [1,2-a] [1,8] naphthyridine, indolo [1,2-b] -2,6-naphthyridine, indolo [1,2-b] [2,7] naphthyridine, indolo [1,2-h] -1,7-naphthyridine, indolo [1,2-b] isoquinoline, indolo [2,1-a] isoquinoline, indolo [1,2-a] quinoline, 2H, 6H-pyrido [2 ′, 1 ′: 3,4] [1,4] diazepino [1,2-a] indole, 1H-indolo [2,1-c] [1,4] benzodiazepine, 2H-indolo [1,2-d] [1,4] benzodiazepine, 2H-indolo [ 2,1-a] [2,3] benzodiazepine, 2H-indolo [2,1-b] [1,3] benzodiazepine, 1H-indolo [1,2-b] [2] benzazepine, 2H-indolo [1 , 2-a] [1] benzazepine, 2H-indolo [2,1-a] [2] benzazepine, indolo [1,2-e] [1,5] benzodiazocine, indolo [2,1-b] [3] A group formed by removing one hydrogen atom from a tetracyclic fused benzene ring such as benzazocine.

〔式中、各記号は前記と同意義を示す。〕で表される基の具体例としては、１Ｈ−イミダゾ〔１'，２'：１,２〕ピリド〔３,４−b〕インドール，１Ｈ−イミダゾ〔１'，２'：１,６〕ピリド〔４,３−b〕インドール，１Ｈ−イミダゾ〔１'，５'：１,２〕ピリド〔３,４−b〕インドール，１Ｈ−イミダゾ〔１'，５'：１,６〕ピリド〔４,３−b〕インドール，１Ｈ−ピリド〔２'，１'：２,３〕イミダゾ〔４,５−b〕インドール，イミダゾ〔４,５−a〕カルバゾール，イミダゾ〔４,５−c〕カルバゾール，ピラゾロ〔３,４−c〕カルバゾール，２Ｈ−ピラジノ〔１'，２'：１,５〕ピロロ〔２,３−b〕インドール，１Ｈ−ピロロ〔１'，２'：１,２〕ピリミド〔４,５−b〕インドール，１Ｈ−インドリジノ〔６,７−b〕インドール，１Ｈ−インドリジノ〔８,７−b〕インドール，インドロ〔２,３−b〕インドール，インドロ〔３,２−b〕インドール，ピロロ〔２,３−a〕カルバゾール，ピロロ〔２,３−b〕カルバゾール，ピロロ〔２,３−c〕カルバゾール，ピロロ〔３,２−a〕カルバゾール，ピロロ〔３,２−b〕カルバゾール，ピロロ〔３,２−c〕カルバゾール，ピロロ〔３,４−a〕カルバゾール，ピロロ〔３,４−b〕カルバゾール，ピロロ〔３,４−c〕カルバゾール，１Ｈ−ピリド〔３'，４'：４,５〕フロ〔３,２−b〕インドール，１Ｈ−フロ〔３,４−a〕カルバゾール，１Ｈ−フロ〔３,４−b〕カルバゾール，１Ｈ−フロ〔３,４−c〕カルバゾール，２Ｈ−フロ〔２,３−a〕カルバゾール，２Ｈ−フロ〔２,３−c〕カルバゾール，２Ｈ−フロ〔３,２−a〕カルバゾール，２Ｈ−フロ〔３,２−c〕カルバゾール，１Ｈ−ピリド〔３'，４'：４,５〕チエノ〔２,３−b〕インドール，チエノ〔３'，２'：５,６〕チオピラノ〔４,３−b〕インドール，チエノ〔３'，４'：５,６〕チオピラノ〔４,３−b〕インドール，１Ｈ−〔１〕ベンゾチエノ〔２,３−blインドール，１Ｈ−〔１〕ベンゾチエノ〔３,２−b〕インドール，１Ｈ−チエノ〔３,４−a〕カルバゾール，２Ｈ−チエノ〔２,３−b〕カルバゾール，２Ｈ−チエノ〔３,２−a〕カルバゾール，２Ｈ−チエノ〔３,２−b〕カルバゾール，シクロペンタ〔４,５〕ピロロ〔２,３−f〕キノキサリン，シクロペンタ〔５,６〕ピリド〔２,３−b〕インドール，ピリド〔２'，３'：３,４〕シクロペンタ〔１,２−b〕インドール，ピリド〔２'，３'：４,５〕シクロペンタ〔１,２−b〕インドール，ピリド〔３'，４'：３,４〕シクロペンタ〔１,２−b〕インドール，ピリド〔３'，４'：４,５〕シクロペンタ〔１,２−b〕インドール，ピリド〔４'，３'：４,５〕シクロペンタ〔１,２−b〕インドール，１Ｈ−シクロペンタ〔５,６〕ピラノ〔２,３−b〕インドール，１Ｈ−シクロペンタ〔５,６〕チオピラノ〔４,３−b〕インドール，シクロペンタ〔a〕カルバゾール，シクロペンタ〔c〕カルバゾール，インデノ〔１,２−b〕インドール，インデノ〔２,１−b〕インドール，〔１,２,４〕トリアジノ〔４'，３'：１,２〕ピリド〔３,４−b〕インドール，１,３,５−トリアジノ〔１'，２'：１,１〕ピリド〔３,４−b〕インドール，１Ｈ−〔１,４〕オキサジノ〔４'，３'：１,２〕ピリド〔３,４−b〕インドール，１Ｈ−〔１,４〕オキサジノ〔４'，３'：１,６〕ピリド〔３,４−b〕インドール，４Ｈ−〔１,３〕オキサジノ〔３'，４'：１,２〕ピリド〔３,４−b〕インドール，インドロ〔３,２−b〕〔１,４〕ベンズオキサジン，１,３−オキサジノ〔６,５−b〕カルバゾール，２Ｈ−ピリミド〔２'，１'：２,３〕〔１,３〕チアジノ〔５,６−b〕インドール，２Ｈ−〔１,３〕チアジノ〔３'，２'：１,２〕ピリド〔３,４−b〕インドール，４Ｈ−〔１,３〕チアジノ〔３'，４'：１,２〕ピリド〔３,４−b〕インドール，インドロ〔２,３−b〕〔１,４〕ベンゾチアジン，インドロ〔３,２−b〕〔１,４〕ベンゾチアジン，インドロ〔３,２−c〕〔２,１〕ベンゾチアジン，１,４−チアジノ〔２,３−a〕カルバゾール，〔１,４〕チアジノ〔２,３−b〕カルバゾール，〔１,４〕チアジノ〔２,３−c〕カルバゾール，１,４−チアジノ〔３,２−b〕カルバゾール，１,４−チアジノ〔３,２−c〕カルバゾール，１Ｈ−インドロ〔２,３−g〕プテリジン，１Ｈ−インドロ〔３,２−g〕プテリジン，ピラジノ〔１'，２'：１,２〕ピリド〔３,４−b〕インドール，ピラジノ〔１'，２'：１,２〕ピリド〔４,３−b〕インドール，１Ｈ−ピリド〔２'，３'：５,６〕ピラジノ〔２,３−b〕インドール，１Ｈ−ピリド〔３'，２'：５,６〕ピラジノ〔２,３−b〕インドール，１Ｈ−ピリド〔３'，４'：５,６〕ピラジノ〔２,３−b〕インドール，ピリド〔１'，２'：１,２〕ピリミド〔４,５−b〕インドール，ピリド〔１'，２'：１,２〕ピリミド〔５,４−b〕インドール，ピリド〔２'，１'：２,３〕ピリミド〔４,５−b〕インドール，ピリミド〔１'，２'：１,２〕ピリド〔３,４−b〕インドール，ピリミド〔１'，２'：１,６〕ピリド〔３,４−b〕インドール，ピリミド〔５'，４'：５,６〕ピラノ〔２,３−b〕インドール，ピリダジノ〔４'，５'：５,６〕チオピラノ〔４,５−b〕インドール，１Ｈ−インドロ〔３,２−c〕シンノリン，１Ｈ−インドロ〔２,３−b〕キノキサリン，１Ｈ−ピラジノ〔２,３−a〕カルバゾール，１Ｈ−ピラジノ〔２,３−b〕カルバゾール，１Ｈ−ピラジノ〔２,３−c〕カルバゾール，１Ｈ−ピリダジノ〔３,４−c〕カルバゾール，１Ｈ−ピリダジノ〔４,５−b〕カルバゾール，１Ｈ−ピリミド〔４,５−a〕カルバゾール，１Ｈ−ピリミド〔４,５−c〕カルバゾール，１Ｈ−ピリミド〔５,４−a〕カルバゾール，１Ｈ−ピリミド〔５,４−b〕カルバゾール，１Ｈ−ピリミド〔５,４−c〕カルバゾール，７Ｈ−１,４−ジオキシノ〔２'，３'：５,６〕〔１,２〕ジオキシノ〔３,４−b〕インドール，６Ｈ−〔１,４〕ベンゾジオキシノ〔２,３−b〕インドール，６Ｈ−〔１,４〕ベンゾジチイノ〔２,３−b〕インドール，１Ｈ−インドロ〔２,３−b〕−１,５−ナフチリジン，１Ｈ−インドロ〔２,３−b〕〔１,６〕ナフチリジン，１Ｈ−インドロ〔２,３−b〕〔１,８〕ナフチリジン，１Ｈ−インドロ〔２,３−c〕−１,５−ナフチリジン，１Ｈ−インドロ〔２,３−c〕〔１,６〕ナフチリジン，１Ｈ−インドロ〔２,３−c〕〔１,７〕ナフチリジン，１Ｈ−インドロ〔２,３−c〕〔１,８〕ナフチリジン，１Ｈ−インドロ〔３,２−b〕−１,５−ナフチリジン，１Ｈ−インドロ〔３,２−b〕〔１,７〕ナフチリジン，１Ｈ−インドロ〔３,２−b〕〔１,８〕ナフチリジン，１Ｈ−インドロ〔３,２−c〕〔１,８〕ナフチリジン，インドロ〔２,３−a〕キノリジン，インドロ〔２,３−b〕キノリジン，インドロ〔３,２−a〕キノリジン，インドロ〔３,２−b〕キノリジン，ピラノ〔４'，３'：５,６〕ピリド〔３,４−b〕インドール，ピリド〔４'，３'：４,５〕ピラノ〔３,２−b〕インドール，ピリド〔４'，３'：５,６〕ピラノ〔２,３−b〕インドール，ピリド〔４'，３'：５,６〕ピラノ〔３,４−b〕インドール，１Ｈ−インドロ〔２,３−c〕イソキノリン，１Ｈ−インドロ〔３,２−c〕イソキノリン，１Ｈ−インドロ〔２,３−c〕キノリン，１Ｈ−インドロ〔３,２−c〕キノリン，１Ｈ−ピリド〔２,３−a〕カルバゾール，１Ｈ−ピリド〔２,３−b〕カルバゾール,１Ｈ−ピリド〔２,３−c〕カルバゾール，１Ｈ−ピリド〔３,２−a〕カルバゾール，１Ｈ−ピリド〔３,２−b〕カルバゾール，１Ｈ−ピリド〔３,２−c〕カルバゾール，１Ｈ−ピリド〔３,４−a〕カルバゾール，１Ｈ−ピリド〔３,４−b〕カルバゾール，１Ｈ−ピリド〔３,４−c〕カルバゾール，１Ｈ−ピリド〔４,３−a〕カルバゾール，１Ｈ−ピリド〔４,３−b〕カルバゾール，１Ｈ−ピリド〔４,３−c〕カルバゾール，１Ｈ−キンドリン，１Ｈ−キニンドリン，１Ｈ−ピラノ〔３'，４'：５,６〕ピラノ〔４,３−b〕インドール，〔１〕ベンゾピラノ〔２,３−b〕インドール，〔１〕ベンゾピラノ〔３,２−b〕インドール，〔１〕ベンゾピラノ〔３,４−b〕インドール，〔１〕ベンゾピラノ〔４,３−b〕インドール，〔２〕ベンゾピラノ〔４,３−b〕インドール，ピラノ〔２,３−a〕カルバゾール，ピラノ〔２,３−b〕カルバゾール，ピラノ〔２,３−c〕カルバゾール，ピラノ〔３,２−a〕カルバゾール，ピラノ〔３,２−c〕カルバゾール，ピラノ〔３,４−a〕カルバゾール，１Ｈ−ホスフィノリノ〔４,３−b〕インドール，〔１〕ベンゾチオピラノ〔２,３−b〕インドール，〔１〕ベンゾチオピラノ〔３,２−b〕インドール，〔１〕ベンゾチオピラノ〔３,４−b〕インドール，〔１〕ベンゾチオピラノ〔４,３−b〕インドール，〔２〕ベンゾチオピラノ〔４,３−b〕インドール，１Ｈ−ベンゾ〔a〕カルバゾール，１Ｈ−ベンゾ〔b〕カルバゾール，１Ｈ−ベンゾ〔c〕カルバゾール，〔１,６,２〕オキサチアゼピノ〔２'，３'：１,２〕ピリド〔３,４−b〕インドール，１Ｈ−アゼピノ〔１'，２'：１,２〕ピリド〔３,４−b〕インドール，１Ｈ−ピリド〔１'，２'：１,２〕アゼピノ〔４,５−b〕インドール，２Ｈ−ピリド〔１'，２'：１,２〕アゼピノ〔３,４−b〕インドール，１Ｈ−ピリド〔３'，２'：５,６〕オキセピノ〔３,２−b〕インドール，１Ｈ−ピリド〔４'，３'：５,６〕オキセピノ〔３,２−b〕インドール，２Ｈ−ピリド〔２'，３'：５,６〕オキセピノ〔２,３−b〕インドール，２Ｈ−ピリド〔２'，３'：５,６〕オキセピノ〔３,２−b〕インドール，２Ｈ−ピリド〔３'，４'：５,６〕オキセピノ〔３,２−b〕インドール，ピリド〔２'，３'：４,５〕シクロヘプタ〔１,２−b〕インドール，ピリド〔３'，２'：３,４〕シクロヘプタ〔１,２−b〕インドール，ピリド〔３'，４'：４,５〕シクロヘプタ〔１,２−b〕インドール，ピリド〔３'，４'：５,６〕シクロヘプタ〔１,２−b〕インドール，２Ｈ−ピラノ〔３'，２'：２,３〕アゼピノ〔４,５−b〕インドール，１Ｈ−インドロ〔３,２−b〕〔１,５〕ベンズオキサゼピン，１Ｈ−インドロ〔３,２−d〕〔１,２〕ベンズオキサゼピン，１Ｈ−インドロ〔２,３−c〕〔１,５〕ベンゾチアゼピン，〔１,４〕ジアゼピノ〔２,３−a〕カルバゾール，インドロ〔２,３−b〕〔１,５〕ベンゾジアゼピン，インドロ〔２,３−d〕〔１,３〕ベンゾジアゼピン，インドロ〔３,２−b〕〔１,４〕ベンゾジアゼピン，インドロ〔３,２−b〕〔１,５〕ベンゾジアゼピン，インドロ〔３,２−d〕〔１,３〕ベンゾジアゼピン，インドロ〔３,２−d〕〔２,３〕ベンゾジアゼピン，インドロ〔２,３−a〕〔３〕ベンズアゼピン，インドロ〔２,３−c〕〔１〕ベンズアゼピン，インドロ〔２,３−d〕〔１〕ベンズアゼピン，インドロ〔２,３−d〕〔２〕ベンズアゼピン，インドロ〔３,２−b〕〔１〕ベンズアゼピン，インドロ〔３,２−c〕〔１〕ベンズアゼピン，インドロ〔３,２−d〕〔１〕ベンズアゼピン，１Ｈ−インドロ〔２,１−b〕〔３〕ベンズアゼピン，１Ｈ−〔１〕ベンズオキセピノ〔５,４−b〕インドール，１Ｈ−〔２〕ベンズオキセピノ〔４,３−b〕インドール，１Ｈ−〔１〕ベンゾチエピノ〔４,５−b〕インドール，１Ｈ−〔１〕ベンゾチエピノ〔５,４−b〕インドール，ベンゾ〔３,４〕シクロヘプタ〔１,２−b〕インドール，ベンゾ〔４,５〕シクロヘプタ〔１,２−b〕インドール，ベンゾ〔５,６〕シクロヘプタ〔１,２−b〕インドール，ベンゾ〔６,７〕シクロヘプタ〔１,２−b〕インドール，シクロヘプタ〔b〕カルバゾール，４Ｈ−〔１,５〕オキサゾシノ〔５'，４'：１,６〕ピリド〔３,４−b〕インドール，アゾシノ〔１'，２'：１,２〕ピリド〔３,４−b〕インドール，２,６−メタノ−２Ｈ−アゼシノ〔４,３−b〕インドール，３,７−メタノ−３Ｈ−アゼシノ〔５,４−b〕インドール，ピリド〔１'，２'：１,８〕アゾシノ〔５,４−b〕インドール，ピリド〔４'，３'：６,７〕オキソシノ〔２,３−b〕インドール，ピリド〔４'，３'：６,７〕オキソシノ〔４,３−b〕インドール，１,５−メタノ−１Ｈ−アゼシノ〔３,４−b〕インドール，２,６−メタノ−１Ｈ−アゼシノ〔５,４−b〕インドール，１Ｈ−ピリド〔３'，４'：５,６〕シクロオクタ〔１,２−b〕インドール，１,４−エタノオキソシノ〔３,４−b〕インドール，ピラノ〔３'，４'：５,６〕シクロオクタ〔１,２−b〕インドール，１Ｈ−インドロ〔２,３−c〕〔１,２,５,６〕ベンゾテトラゾシン，１Ｈ−インドロ〔２,３−c〕〔１,６〕ベンゾジア
ゾシン，６，１３b−メタノ−１３bＨ−アゼシノ〔５,４−b〕インドール，オキソシノ〔３,２−a〕カルバゾール，１Ｈ−ベンゾ〔g〕シクロオクタ〔b〕インドール，６,３−（イミノメタノ）−２Ｈ−１,４−チアゾニノ〔９,８−b〕インドール，１Ｈ，３Ｈ−〔１,４〕オキサゾニノ〔４'，３'：１,２〕ピリド〔３,４−b〕インドール，２Ｈ−３,６−エタノアゾニノ〔５,４−b〕インドール，２Ｈ−３,７−メタノアザシクロウンデシノ〔５,４−b〕インドール，１Ｈ−６,１２b−エタノアゾニノ〔５,４−b〕インドール，インドロ〔３,２−e〕〔２〕ベンズアゾニン，５,９−メタノアザシクロウンデシノ〔５,４−b〕インドール，３,６−エタノ−３Ｈ−アゼシノ〔５,４−b〕インドール，３,７−メタノ−３Ｈ−アザシクロウンデシノ〔５,４−b〕インドール，ピラノ〔４'，３'：８,９〕アゼシノ〔５,４−b〕インドール，１Ｈ−インドロ〔２,３−c〕〔１,７〕ベンゾジアゼシン，１Ｈ−インドロ〔３,２−e〕〔２〕ベンズアゼシン，ベンゾ〔e〕ピロロ〔３,２−b〕インドール，ベンゾ〔e〕ピロロ〔３,２−g〕インドール，ベンゾ〔e〕ピロロ〔３,２,１−hi〕インドール，ベンゾ〔e〕ピロロ〔３,４−b〕インドール，ベンゾ〔g〕ピロロ〔３,４−b〕インドール，１Ｈ−ベンゾ〔f〕ピロロ〔１,２−a〕インドール，１Ｈ−ベンゾ〔g〕ピロロ〔１,２−a〕インドール，２Ｈ−ベンゾ〔e〕ピロロ〔１,２−a〕インドール，１Ｈ−ベンゾ〔f〕ピロロ〔２,１−a〕イソインドール，１Ｈ−ベンゾ〔g〕ピロロ〔２,１−a〕イソインドール，２Ｈ−ベンゾ〔e〕ピロロ〔２,１−a〕イソインドール，イソインドロ〔６,７,１−cde〕インドール，スピロ〔シクロヘキサン−１,５'−〔５Ｈ〕ピロロ〔２,１−a〕イソインドール〕，イソインドロ〔７,１,２−hij〕キノリン，７,１１−メタノアゾシノ〔１,２−a〕インドール，７,１１−メタノアゾシノ〔２,１−a〕イソインドール，ジベンズ〔cd,f〕インドール，ジベンズ〔cd,g〕インドール，ジベンズ〔d,f〕インドール，１Ｈ−ジベンズ〔e,g〕インドール，１Ｈ−ジベンズ〔e,g〕イソインドール，ナフト〔１,２,３−cd〕インドール，ナフト〔１,８−ef〕インドール，ナフト〔１,８−fg〕インドール，ナフト〔３,２,１−cd〕インドール，１Ｈ−ナフト〔１,２−e〕インドール，１Ｈ−ナフト〔１,２−f〕インドール，１Ｈ−ナフト〔１,２−g〕インドール，１Ｈ−ナフト〔２,１−e〕インドール，１Ｈ−ナフト〔２,３−e〕インドール，１Ｈ−ナフト〔１,２−f〕イソインドール，１Ｈ−ナフト〔２,３−e〕イソインドール，スピロ〔１Ｈ−カルバゾール−１,１'−シクロヘキサン〕，スピロ〔２Ｈ−カルバゾール−２,１'−シクロヘキサン〕，スピロ〔３Ｈ−カルバゾール−３,１'−シクロヘキサン〕，シクロヘプタ〔４,５〕ピロロ〔３,２−f〕キノリン，シクロヘプタ〔４,５〕ピロロ〔３,２−h〕キノリン，アゼピノ〔４,５−b〕ベンズ〔e〕インドール，１Ｈ−アゼピノ〔１,２−a〕ベンズ〔f〕インドール，１Ｈ−アゼピノ〔２,１−a〕ベンズ〔f〕イソインドール，ベンゾ〔e〕シクロヘプタ〔b〕インドール，ベンゾ〔g〕シクロヘプタ〔b〕インドール等の４環式縮合ベンゼン環から水素原子を１個除去してできる基が挙げられる。 Above formula

[Wherein each symbol is as defined above. As specific examples of the group represented by the formula: 1H-imidazo [1 ', 2': 1,2] pyrido [3,4-b] indole, 1H-imidazo [1 ', 2': 1,6] Pyrido [4,3-b] indole, 1H-imidazo [1 ′, 5 ′: 1,2] pyrido [3,4-b] indole, 1H-imidazo [1 ′, 5 ′: 1,6] pyrido [ 4,3-b] indole, 1H-pyrido [2 ′, 1 ′: 2,3] imidazo [4,5-b] indole, imidazo [4,5-a] carbazole, imidazo [4,5-c] Carbazole, pyrazolo [3,4-c] carbazole, 2H-pyrazino [1 ′, 2 ′: 1,5] pyrrolo [2,3-b] indole, 1H-pyrrolo [1 ′, 2 ′: 1,2] Pyrimido [4,5-b] indole, 1H-indolidino [6,7-b] indole, 1H-indolidino [8,7-b] indole, indolo [2,3-b] i Dole, indolo [3,2-b] indole, pyrrolo [2,3-a] carbazole, pyrrolo [2,3-b] carbazole, pyrrolo [2,3-c] carbazole, pyrrolo [3,2-a] Carbazole, pyrrolo [3,2-b] carbazole, pyrrolo [3,2-c] carbazole, pyrrolo [3,4-a] carbazole, pyrrolo [3,4-b] carbazole, pyrrolo [3,4-c] Carbazole, 1H-pyrido [3 ′, 4 ′: 4,5] furo [3,2-b] indole, 1H-furo [3,4-a] carbazole, 1H-furo [3,4-b] carbazole, 1H-furo [3,4-c] carbazole, 2H-furo [2,3-a] carbazole, 2H-furo [2,3-c] carbazole, 2H-furo [3,2-a] carbazole, 2H- Furo [3,2-c] carbazole, 1H-pyrido [3 ′, 4 ′: 4,5] thieno [2 , 3-b] indole, thieno [3 ′, 2 ′: 5,6] thiopyrano [4,3-b] indole, thieno [3 ′, 4 ′: 5,6] thiopyrano [4,3-b] indole , 1H- [1] benzothieno [2,3-blindole, 1H- [1] benzothieno [3,2-b] indole, 1H-thieno [3,4-a] carbazole, 2H-thieno [2,3- b] carbazole, 2H-thieno [3,2-a] carbazole, 2H-thieno [3,2-b] carbazole, cyclopenta [4,5] pyrrolo [2,3-f] quinoxaline, cyclopenta [5,6] Pyrido [2,3-b] indole, pyrido [2 ′, 3 ′: 3,4] cyclopenta [1,2-b] indole, pyrido [2 ′, 3 ′: 4,5] cyclopenta [1,2- b] Indole, pyrido [3 ', 4': 3,4] cyclopenta [1,2-b] indole, pyrido [3 ', 4': 4,5] cyclopenta [1,2-b] indole, pyrido [4 ', 3': 4,5] cyclopenta [1,2-b] indole, 1H-cyclopenta [5,6] pyrano [2,3-b] indole, 1H-cyclopenta [5,6] thiopyrano [4,3-b] indole, cyclopenta [a] carbazole, cyclopenta [c] carbazole, indeno [1,2-b] indole, indeno [2,1-b] indole, [1,2,4] triazino [4 ′, 3 ′: 1,2] pyrido [3,4-b] indole, 1,3,5-triazino [1 ′, 2 ': 1,1] pyrido [3,4-b] indole, 1H- [1,4] oxazino [4', 3 ': 1,2] pyrido [3,4-b] indole, 1H- [1, 4] Oxazino [4 ′, 3 ′: 1,6] pyrido [3,4-b] indole, 4H- [1,3] oxazino [3 ′, 4 ′: 1, 2] pyrido [3,4-b] indole, indolo [3,2-b] [1,4] benzoxazine, 1,3-oxazino [6,5-b] carbazole, 2H-pyrimido [2 ', 1 ': 2,3] [1,3] thiazino [5,6-b] indole, 2H- [1,3] thiazino [3', 2 ': 1,2] pyrido [3,4-b] indole, 4H- [1,3] thiazino [3 ′, 4 ′: 1,2] pyrido [3,4-b] indole, indolo [2,3-b] [1,4] benzothiazine, indolo [3,2- b] [1,4] benzothiazine, indolo [3,2-c] [2,1] benzothiazine, 1,4-thiazino [2,3-a] carbazole, [1,4] thiazino [2,3-b Carbazole, [1,4] thiazino [2,3-c] carbazole, 1,4-thiazino [3,2-b] carbazole, 1,4-thiazino [3,2-c] carbazol , 1H-indolo [2,3-g] pteridine, 1H-indolo [3,2-g] pteridine, pyrazino [1 ′, 2 ′: 1,2] pyrido [3,4-b] indole, pyrazino [1 ', 2': 1,2] pyrido [4,3-b] indole, 1H-pyrido [2 ', 3': 5,6] pyrazino [2,3-b] indole, 1H-pyrido [3 ', 2 ′: 5,6] pyrazino [2,3-b] indole, 1H-pyrido [3 ′, 4 ′: 5,6] pyrazino [2,3-b] indole, pyrido [1 ′, 2 ′: 1 , 2] pyrimido [4,5-b] indole, pyrido [1 ′, 2 ′: 1,2] pyrimido [5,4-b] indole, pyrido [2 ′, 1 ′: 2,3] pyrimido [4 , 5-b] indole, pyrimido [1 ′, 2 ′: 1,2] pyrido [3,4-b] indole, pyrimido [1 ′, 2 ′: 1,6] pyrido [3,4-b] indole , Pyrimido [5 ', 4' 5,6] pyrano [2,3-b] indole, pyridazino [4 ', 5': 5,6] thiopyrano [4,5-b] indole, 1H-indolo [3,2-c] cinnoline, 1H- Indolo [2,3-b] quinoxaline, 1H-pyrazino [2,3-a] carbazole, 1H-pyrazino [2,3-b] carbazole, 1H-pyrazino [2,3-c] carbazole, 1H-pyridazino [ 3,4-c] carbazole, 1H-pyridazino [4,5-b] carbazole, 1H-pyrimido [4,5-a] carbazole, 1H-pyrimido [4,5-c] carbazole, 1H-pyrimido [5, 4-a] carbazole, 1H-pyrimido [5,4-b] carbazole, 1H-pyrimido [5,4-c] carbazole, 7H-1,4-dioxino [2 ′, 3 ′: 5,6] [1 , 2] dioxino [3,4-b] indole, 6H- [1, Benzodioxino [2,3-b] indole, 6H- [1,4] benzodithino [2,3-b] indole, 1H-indolo [2,3-b] -1,5-naphthyridine, 1H-indolo [2] , 3-b] [1,6] naphthyridine, 1H-indolo [2,3-b] [1,8] naphthyridine, 1H-indolo [2,3-c] -1,5-naphthyridine, 1H-indolo [ 2,3-c] [1,6] naphthyridine, 1H-indolo [2,3-c] [1,7] naphthyridine, 1H-indolo [2,3-c] [1,8] naphthyridine, 1H-indolo [3,2-b] -1,5-naphthyridine, 1H-indolo [3,2-b] [1,7] naphthyridine, 1H-indolo [3,2-b] [1,8] naphthyridine, 1H- Indolo [3,2-c] [1,8] naphthyridine, indolo [2,3-a] quinolidine, indolo [2, 3-b] quinolidine, indolo [3,2-a] quinolidine, indolo [3,2-b] quinolidine, pyrano [4 ′, 3 ′: 5,6] pyrido [3,4-b] indole, pyrido [ 4 ′, 3 ′: 4,5] pyrano [3,2-b] indole, pyrido [4 ′, 3 ′: 5,6] pyrano [2,3-b] indole, pyrido [4 ′, 3 ′: 5,6] pyrano [3,4-b] indole, 1H-indolo [2,3-c] isoquinoline, 1H-indolo [3,2-c] isoquinoline, 1H-indolo [2,3-c] quinoline, 1H-indolo [3,2-c] quinoline, 1H-pyrido [2,3-a] carbazole, 1H-pyrido [2,3-b] carbazole, 1H-pyrido [2,3-c] carbazole, 1H- Pyrido [3,2-a] carbazole, 1H-pyrido [3,2-b] carbazole, 1H-pyrido [3,2-c] carbazole, 1H-pyrido [3,4-a] carbazole, 1H-pyrido [3,4-b] carbazole, 1H-pyrido [3,4-c] carbazole, 1H-pyrido [4,3-a] carbazole, 1H- Pyrido [4,3-b] carbazole, 1H-pyrido [4,3-c] carbazole, 1H-kindrin, 1H-quinindrine, 1H-pyrano [3 ′, 4 ′: 5,6] pyrano [4,3- b) indole, [1] benzopyrano [2,3-b] indole, [1] benzopyrano [3, 2-b] indole, [1] benzopyrano [3,4-b] indole, [1] benzopyrano [4, 3-b] indole, [2] benzopyrano [4,3-b] indole, pyrano [2,3-a] carbazole, pyrano [2,3-b] carbazole, pyrano [2,3-c] carbazole, pyrano [3,2-a] carbazole, pyrano [3,2 c] carbazole, pyrano [3,4-a] carbazole, 1H-phosphinolino [4,3-b] indole, [1] benzothiopyrano [2,3-b] indole, [1] benzothiopyrano [3,2-b] Indole, [1] benzothiopyrano [3,4-b] indole, [1] benzothiopyrano [4,3-b] indole, [2] benzothiopyrano [4,3-b] indole, 1H-benzo [a] carbazole, 1H -Benzo [b] carbazole, 1H-benzo [c] carbazole, [1,6,2] oxathiazepino [2 ', 3': 1,2] pyrido [3,4-b] indole, 1H-azepino [1 ' , 2 ': 1,2] pyrido [3,4-b] indole, 1H-pyrido [1', 2 ': 1,2] azepino [4,5-b] indole, 2H-pyrido [1', 2 ': 1,2] Azepino [3,4-b] India , 1H-pyrido [3 ′, 2 ′: 5,6] oxepino [3,2-b] indole, 1H-pyrido [4 ′, 3 ′: 5,6] oxepino [3,2-b] indole, 2H -Pyrido [2 ', 3': 5,6] oxepino [2,3-b] indole, 2H-pyrido [2 ', 3': 5,6] oxepino [3,2-b] indole, 2H-pyrido [3 ′, 4 ′: 5,6] oxepino [3,2-b] indole, pyrido [2 ′, 3 ′: 4,5] cyclohepta [1,2-b] indole, pyrido [3 ′, 2 ′ : 3,4] cyclohepta [1,2-b] indole, pyrido [3 ', 4': 4,5] cyclohepta [1,2-b] indole, pyrido [3 ', 4': 5,6] cyclohepta [1,2-b] indole, 2H-pyrano [3 ′, 2 ′: 2,3] azepino [4,5-b] indole, 1H-indolo [3,2-b] [1,5] benzoxase Pin, 1H-indolo [3,2-d] [1,2] benzoxazepine, 1H-indolo [2,3-c] [1,5] benzothiazepine, [1,4] diazepino [2, 3-a] carbazole, indolo [2,3-b] [1,5] benzodiazepine, indolo [2,3-d] [1,3] benzodiazepine, indolo [3,2-b] [1,4] benzodiazepine , Indolo [3,2-b] [1,5] benzodiazepine, indolo [3,2-d] [1,3] benzodiazepine, indolo [3,2-d] [2,3] benzodiazepine, indolo [2, 3-a] [3] benzazepine, indolo [2,3-c] [1] benzazepine, indolo [2,3-d] [1] benzazepine, indolo [2,3-d] [2] benzazepine, indolo [ 3,2-b] [1] benzazepine, indolo [3,2-c] [1] Zazepine, indolo [3,2-d] [1] benzazepine, 1H-indolo [2,1-b] [3] benzazepine, 1H- [1] benzoxepino [5,4-b] indole, 1H- [2] Benzoxepino [4,3-b] indole, 1H- [1] benzothiepino [4,5-b] indole, 1H- [1] benzothiepino [5,4-b] indole, benzo [3,4] cyclohepta [1, 2-b] indole, benzo [4,5] cyclohepta [1,2-b] indole, benzo [5,6] cyclohepta [1,2-b] indole, benzo [6,7] cyclohepta [1,2- b] indole, cyclohepta [b] carbazole, 4H- [1,5] oxazosino [5 ', 4': 1,6] pyrido [3,4-b] indole, azosino [1 ', 2': 1, 2 ] Pyrido [3,4-b] indole, 2, -Methano-2H-azecino [4,3-b] indole, 3,7-methano-3H-azecino [5,4-b] indole, pyrido [1 ', 2': 1,8] azosino [5,4 -B] indole, pyrido [4 ', 3': 6,7] oxosino [2,3-b] indole, pyrido [4 ', 3': 6,7] oxosino [4,3-b] indole, 1 , 5-methano-1H-azecino [3,4-b] indole, 2,6-methano-1H-azecino [5,4-b] indole, 1H-pyrido [3 ′, 4 ′: 5,6] cycloocta [1,2-b] indole, 1,4-ethanooxosino [3,4-b] indole, pyrano [3 ′, 4 ′: 5,6] cycloocta [1,2-b] indole, 1H-indolo [2 , 3-c] [1,2,5,6] benzotetrazocine, 1H-indolo [2,3-c] [1,6] benzodiazocine, 6,13b Methano-13bH-azecino [5,4-b] indole, oxosino [3,2-a] carbazole, 1H-benzo [g] cycloocta [b] indole, 6,3- (iminomethano) -2H-1,4- Thiazino [9,8-b] indole, 1H, 3H- [1,4] oxazonino [4 ', 3': 1,2] pyrido [3,4-b] indole, 2H-3,6-ethanoazino [5 , 4-b] indole, 2H-3,7-methanoazacycloundecino [5,4-b] indole, 1H-6,12b-ethanoazino [5,4-b] indole, indolo [3,2-e ] [2] Benzazonin, 5,9-methanoazacycloundecino [5,4-b] indole, 3,6-ethano-3H-azecino [5,4-b] indole, 3,7-methano-3H- Azacycloundecino [5,4-b] indole, pyrano [ ', 3': 8,9] azeno [5,4-b] indole, 1H-indolo [2,3-c] [1,7] benzodiazecin, 1H-indolo [3,2-e] [2] benzazecine Benzo [e] pyrrolo [3,2-b] indole, benzo [e] pyrrolo [3,2-g] indole, benzo [e] pyrrolo [3,2,1-hi] indole, benzo [e] pyrrolo [3,4-b] indole, benzo [g] pyrrolo [3,4-b] indole, 1H-benzo [f] pyrrolo [1,2-a] indole, 1H-benzo [g] pyrrolo [1,2 -A] indole, 2H-benzo [e] pyrrolo [1,2-a] indole, 1H-benzo [f] pyrrolo [2,1-a] isoindole, 1H-benzo [g] pyrrolo [2,1- a) Isoindole, 2H-benzo [e] pyrrolo [2,1-a] isoindole, isoindolo [6,7,1-cde] i Ndole, spiro [cyclohexane-1,5 '-[5H] pyrrolo [2,1-a] isoindole], isoindolo [7,1,2-hij] quinoline, 7,11-methanoazoshino [1,2-a] Indole, 7,11-methanoazocino [2,1-a] isoindole, dibenz [cd, f] indole, dibenz [cd, g] indole, dibenz [d, f] indole, 1H-dibenz [e, g] indole , 1H-Dibenz [e, g] isoindole, naphtho [1,2,3-cd] indole, naphtho [1,8-ef] indole, naphtho [1,8-fg] indole, naphtho [3,2, 1-cd] indole, 1H-naphtho [1,2-e] indole, 1H-naphtho [1,2-f] indole, 1H-naphtho [1,2-g] indole, 1H-naphtho [2,1- e] Indole, 1H-naphtho [2,3-e] indole 1H-naphtho [1,2-f] isoindole, 1H-naphtho [2,3-e] isoindole, spiro [1H-carbazole-1,1′-cyclohexane], spiro [2H-carbazole-2,1 ′ -Cyclohexane], spiro [3H-carbazole-3,1'-cyclohexane], cyclohepta [4,5] pyrrolo [3,2-f] quinoline, cyclohepta [4,5] pyrrolo [3,2-h] quinoline, Azepino [4,5-b] benz [e] indole, 1H-azepino [1,2-a] benz [f] indole, 1H-azepino [2,1-a] benz [f] isoindole, benzo [e And a group formed by removing one hydrogen atom from a tetracyclic fused benzene ring such as cyclohepta [b] indole and benzo [g] cyclohepta [b] indole.

〔式中、各記号は前記と同意義を示す。〕で表される基の具体例としては、１Ｈ−ジピロロ〔２，３−ｂ：３'，２'，１'−ｈｉ〕インドール，スピロ〔シクロペンタン−１，２'（１'Ｈ）−ピロロ〔３，２，１−ｈｉ〕インドール〕，スピロ〔イミダゾリジン−４，１'（２'Ｈ）−〔４Ｈ〕ピロロ〔３，２，１−ｉｊ〕キノリン〕，ピリド〔２，３−ｂ〕ピロロ〔３，２，１−ｈｉ〕インドール，ピリド〔４，３−ｂ〕ピロロ〔３，２，１−ｈｉ〕インドール，ベンゾ〔ｄｅ〕ピロロ〔３，２，１−ｉｊ〕キノリン，３Ｈ−ピロロ〔３，２，１−ｄｅ〕アクリジン，１Ｈ−ピロロ〔３，２，１−ｄｅ〕フェナントリジン，スピロ〔シクロヘキサン−１，６'−〔６Ｈ〕ピロロ〔３，２，１−ｉｊ〕キノリン〕，４，９−メタノピロロ〔３，２，１−ｌｍ〕〔１〕ベンゾアゾシン，スピロ〔シクロヘプタン−１，６'−〔６Ｈ〕ピロロ〔３，２，１−ｉｊ〕キノリン〕，１Ｈ−ピラノ〔３，４−ｄ〕ピロロ〔３，２，１−ｊｋ〕〔１〕ベンズアゼピン，３Ｈ−ベンゾ〔ｂ〕ピロロ〔３，２，１−ｊｋ〕〔４，１〕ベンズオキサゼピン，７Ｈ−インドロ〔１，７−ａｂ〕〔４，１〕ベンズオキサゼピン，ベンゾ〔ｂ〕ピロロ〔３，２，１−ｊｋ〕〔１，４〕ベンゾジアゼピン，インドロ〔１，７−ａｂ〕〔１，４〕ベンゾジアゼピン，インドロ〔１，７−ａｂ〕〔１〕ベンズアゼピン，インドロ〔７，１−ａｂ〕〔３〕ベンズアゼピン，１Ｈ−シクロヘプタ〔ｄ〕〔３，２，１−ｊｋ〕〔１〕ベンズアゼピン，スピロ〔アゼピノ〔３，２，１−ｈｉ〕インドール−７（４Ｈ），１'−シクロヘプタン〕，４Ｈ−５，１１−メタノピロロ〔３，２，１−ｎｏ〕〔１〕ベンズアザシクロウンデシン，スピロ〔アゼピノ〔３，２，１−ｈｉ〕インドール−７（４Ｈ），１'−シクロオクタン〕等の４環式縮合ベンゼン環から水素原子を１個除去してできる基等が挙げられる。
このうち、更に好ましくは、式

で表される基等である。 Above formula

[Wherein each symbol is as defined above. Specific examples of the group represented by the formula: 1H-dipyrolo [2,3-b: 3 ′, 2 ′, 1′-hi] indole, spiro [cyclopentane-1,2 ′ (1′H) — Pyrrolo [3,2,1-hi] indole], spiro [imidazolidine-4,1 ′ (2′H)-[4H] pyrrolo [3,2,1-ij] quinoline], pyrido [2,3- b] pyrrolo [3,2,1-hi] indole, pyrido [4,3-b] pyrrolo [3,2,1-hi] indole, benzo [de] pyrrolo [3,2,1-ij] quinoline, 3H-pyrrolo [3,2,1-de] acridine, 1H-pyrrolo [3,2,1-de] phenanthridine, spiro [cyclohexane-1,6 ′-[6H] pyrrolo [3,2,1- ij] quinoline], 4,9-methanopyrrolo [3,2,1-lm] [1] benzoazocine, spin [Cycloheptane-1,6 ′-[6H] pyrrolo [3,2,1-ij] quinoline], 1H-pyrano [3,4-d] pyrrolo [3,2,1-jk] [1] benzazepine, 3H-benzo [b] pyrrolo [3,2,1-jk] [4,1] benzoxazepine, 7H-indolo [1,7-ab] [4,1] benzoxazepine, benzo [b] Pyrrolo [3,2,1-jk] [1,4] benzodiazepine, indolo [1,7-ab] [1,4] benzodiazepine, indolo [1,7-ab] [1] benzazepine, indolo [7,1 -Ab] [3] benzazepine, 1H-cyclohepta [d] [3,2,1-jk] [1] benzazepine, spiro [azepino [3,2,1-hi] indole-7 (4H), 1'- Cycloheptane], 4H-5,11-methanopyro Tetracyclic condensed benzene such as [3,2,1-no] [1] benzazacycloundecin, spiro [azepino [3,2,1-hi] indole-7 (4H), 1'-cyclooctane] And a group formed by removing one hydrogen atom from the ring.
Of these, more preferably, the formula

It is group represented by these.

In addition, when the “aromatic ring group” of the “optionally condensed 5- or 6-membered aromatic ring group” represented by Ar is, for example, “aromatic heterocyclic group”, the “aromatic heterocyclic group” is condensed. For example, for example,
(D) when condensed with an optionally substituted monocyclic aromatic ring,
(E) The case of condensing with an optionally substituted bicyclic to tricyclic aromatic ring, or condensing with two identical or different monocyclic aromatic rings.
Specifically, 1-, 2- or 3-indolyl; 1-, 2- or 3-isoindolyl; 2- or 3-benzofuranyl; 2- or 3-benzothiofuranyl; 1- or 3-benzimidazolyl; 2-benzoxazolyl; 2-benzothiazolyl; 1,2-benzisothiazol-3-yl; 1,2-benzisoxazol-3-yl; 2-, 3- or 4-quinolyl; -Or 4-isoquinolyl; 2- or 3-quinoxalinyl; 1- or 4-phthalazinyl; for example, naphthyridinyl such as 1,8-naphthyridin-2-yl, 1,5-naphthyridin-3-yl; 2- or 4- Quinazolinyl; 3- or 4-cinnolinyl; 9-acridinyl; 2-, 6- or 8-purinyl; 2-, 4-, 6- or 8-pteridinyl and the like.

〔式中、Ａ'環はＡ環と同意義を、その他の記号は前記と同意義を示す。〕で表される基である。
ここで、Ａ環およびＡ'環としては、(i)ハロゲン（フルオロ等）、(ii)Ｃ_1-6アルコキシ（メトキシ等）、(iii)ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ等）、(iv)アミノ、(v)（モノ又はジ）Ｃ_1-6アルキルアミノ（メチルアミノ、エチルアミノ、ジメチルアミノ、ジエチルアミノ等）、(vi)1-ピロリジニル、(vii)ピペリジノ、(viii)1-ピペラジニル、(ix)Ｎ−メチル-1-ピペラジニル、(x)Ｎ−アセチル-1-ピペラジニル、(xi)モルホリノ、(xii)ヘキサメチレンイミノ、(xiii)イミダゾリル、(xiv)Ｃ_1-6アルキル（メチル等）でエステル化されていてもよいカルボキシで置換されていてもよいＣ_1-6アルキル（プロピル等）、（xv）低級アルキル−カルボニルアミノ（アセチルアミノ等）、（xvi）低級アルキルスルホニルアミノ（メチルスルホニルアミノ等）,（xvii）アミノスルホニル、(xviii) （モノ又はジ）Ｃ_1-6アルキルアミノスルホニル、(xix)５ないし７員環状アミノ−スルホニル（ (1-ピロリジニル) スルホニル、ピペリジノスルホニル、(1-ピペラジニル) スルホニル、モルホリノスルホニル等）（xx）カルバモイル、(xxi) （モノ又はジ）Ｃ_1-6アルキルカルバモイル、(xxi)５ないし７員環状アミノ−カルボニル（ (1-ピロリジニル) カルボニル、ピペリジノカルボニル、(1-ピペラジニル) カルボニル、モルホリノカルボニル等）、(xxii)シアノ等から選ばれる１ないし４個の置換基を有していてもよいベンゼン環が好ましい。より好ましくはＡ環がアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、カルバモイルおよびモノ−又はジ−Ｃ₁₋₆アルキル−カルバモイルから選ばれる１または２個の置換基を有していてもよいベンゼン環で、Ａ'環がアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、Ｃ₁₋₆アルキル−カルボニルアミノおよびＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有し、さらに１ないし４個の置換基（例えば、Ｃ₁₋₆アルコキシ等）を有していてもよいベンゼン環である。 Ar is preferably, for example, of the formula

[Wherein, the A ′ ring has the same meaning as the A ring, and the other symbols have the same meaning as described above. ] Is a group represented by
Here, the A ring and the A ′ ring include (i) halogen (fluoro etc.), (ii) C _1-6 alkoxy (methoxy etc.), (iii) halogeno C _1-6 alkoxy (trifluoromethoxy etc.), (iv) amino, (v) (mono or di) C _1-6 alkylamino (methylamino, ethylamino, dimethylamino, diethylamino, etc.), (vi) 1-pyrrolidinyl, (vii) piperidino, (viii) 1- Piperazinyl, (ix) N-methyl-1-piperazinyl, (x) N-acetyl-1-piperazinyl, (xi) morpholino, (xii) hexamethyleneimino, (xiii) imidazolyl, (xiv) C _1-6 alkyl ( C _1-6 alkyl (propyl etc.) optionally substituted with carboxy which may be esterified with methyl etc., (xv) lower alkyl-carbonylamino (acetylamino etc.), (xvi) lower alkylsulfonylamino (Such as methylsulfonylamino), (xv ii) aminosulfonyl, (xviii) (mono or di) C _1-6 alkylaminosulfonyl, (xix) 5- to 7-membered cyclic amino-sulfonyl ((1-pyrrolidinyl) sulfonyl, piperidinosulfonyl, (1-piperazinyl) Sulfonyl, morpholinosulfonyl, etc.) (xx) carbamoyl, (xxi) (mono or di) C _1-6 alkylcarbamoyl, (xxi) 5- to 7-membered cyclic amino-carbonyl ((1-pyrrolidinyl) carbonyl, piperidinocarbonyl, (1-piperazinyl) carbonyl, morpholinocarbonyl, etc.), (xxii) a benzene ring optionally having 1 to 4 substituents selected from cyano and the like is preferable. More preferably, the A ring has 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. 1 or 2 of the benzene rings, wherein the A ′ ring is selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino And a benzene ring optionally having 1 to 4 substituents (for example, C _1-6 alkoxy and the like).

In addition, the Ba ring, C ″ ring and D ″ ring each have 1 or 2 substituents selected from C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. at best, R ¹ and R ^{1 'are} each (1) a hydrogen atom, (2), respectively hydroxy and C _1-6 alkoxy - which may have 1 or 2 substituents selected from carbonyl C _{1 -6} alkyl group or C _7-16 aralkyl group or (3) _Formula- (C = O) -R ^{2 '} ,-(C = O) -NR ^2' R ^{3 '} or -SO ₂ R ^2' , R ^{2 ′} and R ^{3 ′} each represent a hydrogen atom, an optionally halogenated C _1-6 alkyl or C _6-10 aryl. ] Which is group represented by these is preferable.

The “spacer having 1 to 10 main chain atoms” in the “optionally substituted spacer having 1 to 10 main chain atoms” represented by L is 1 to 10 main chain atoms. It means a continuous interval. Here, the “number of main chain atoms” is counted so that the main chain atoms are minimized. For example, the number of atoms of 1,2-cyclopentylene is counted as 2, and the number of atoms of 1,3-cyclopentylene is counted as 3.
Examples of the “spacer having 1 to 10 atoms in the main chain which may have a substituent” include, for example, —O—, —S—, —CO—, —SO—, —SO ₂ —, —NR ¹⁰ —. (R ¹⁰ represents a hydrogen atom, an _optionally halogenated C _1-10 alkyl, an _optionally halogenated C _1-6 alkyl-carbonyl, or an optionally halogenated C _1-6 alkylsulfonyl. A divalent C _1-10 acyclic hydrocarbon group which may have a substituent, a divalent C _3-9 cyclic hydrocarbon group which may have a substituent, and a substituent. And a combination of 1 to 5, preferably 1 to 3, of divalent groups selected from divalent heterocyclic groups which may be used.
“Substituent” in “spacer having 1 to 10 atoms in the main chain which may have a substituent”, that is, “divalent C _1-10 acyclic carbonization which may have a substituent” “Substituent” in “hydrogen group”, “divalent C _3-9 cyclic hydrocarbon group _optionally having substituent” and “divalent heterocyclic group optionally having substituent” Is, for example, a halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), oxo, C _1-3 alkylenedioxy (eg, methylenedioxy, ethylenedioxy, etc.), nitro, cyano, halogenated Good C _1-6 alkoxy, optionally halogenated C _1-6 alkylthio, hydroxy, amino, mono- or di-C _1-6 alkylamino, formyl, carboxy, carbamoyl, thiocarbamoyl, halogenated also C _1-6 alkyl - carbonyl C _1-6 alkoxy - carbonyl, mono- - or di -C _1-6 alkyl - carbamoyl, optionally halogenated C _1-6 alkylsulfonyl, formylamino, C _1-6 alkyl which may be halogenated Carboxamide, C _1-6 alkoxy-carboxamide, C _1-6 alkylsulfonylamino, C _1-6 alkyl-carbonyloxy, C _1-6 alkoxy-carbonyloxy, mono-, di-C _1-6 alkyl-carbamoyloxy And 1 to 5, preferably 1 to 3 substituents selected from phenyl and the like. Of these, halogen atoms such as fluorine, oxo, hydroxy, phenyl and the like are preferable.
The “divalent C _1-10 acyclic hydrocarbon group” of the “divalent C _1-10 acyclic hydrocarbon group which may have a substituent” includes C _1-10 alkylene, C Examples include _2-10 alkenylene and C _2-10 alkynylene.
Examples of the “C _1-10 alkylene” include —CH ₂ —, — (CH ₂ ) ₂ —, — (CH ₂ ) ₃ —, — (CH ₂ ) ₄ —, — (CH ₂ ) ₅ —, — (CH ₂ ) ₆ -,-(CH ₂ ) ₇ -,-(CH ₂ ) ₈ -,-(CH ₂ ) ₉ -,-(CH ₂ ) ₁₀ -,-(CH ₂ ) ₃ CH (CH ₃ ) _{-, - (CH 2) 4} CH (CH 3) -, - (CH 3) CHCH 2 -, - (CH 3) CH (CH 2) 2 -, - (CH (CH 3)) 2 - , and the like It is done.
Examples of “C _2-10 alkenylene” include —CH═CH—, —CH ₂ —CH═CH—, —C (CH ₃ ) ₂ —CH═CH—, —CH ₂ —CH═CH—CH _{2. -, - CH 2 -CH 2 -CH} = CH -, - CH = CH-CH = CH -, - CH = CH-CH 2 -CH 2 -CH 2 - and the like.
Examples of “C _2-10 alkynylene” include —C≡C—, —CH ₂ —C≡C—, —CH ₂ —C≡C—CH ₂ —CH ₂ —, and the like.

等が挙げられる。
「C_３−９シクロアルケニレン」としては、

等が挙げられる。 The “divalent C _3-9 cyclic hydrocarbon group” of the “divalent C _3-9 cyclic hydrocarbon group _optionally having substituent (s)” includes C _3-9 cycloalkylene, C _3-9 And cycloalkenylene, C _6-14 arylene (such as phenylene), and the like.
As “C _3-9 cycloalkylene”,

Etc.
As “C _3-9 cycloalkenylene”,

Etc.

  The “divalent heterocyclic group” of the “divalent heterocyclic group optionally having substituents” includes, for example, 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Or a group formed by removing two hydrogen atoms from a 14-membered (preferably 5- to 9-membered) aromatic or non-aromatic heterocyclic ring. Examples of the aromatic or non-aromatic heterocyclic ring include those exemplified in the above-mentioned “heterocyclic ring optionally having substituent (s)” represented by the B ring.

など）も好ましい。 L is preferably a C _1-10 alkylene which may have a substituent, and in particular, may have 1 to 4 substituents selected from a halogen atom, hydroxy, oxo, phenyl and the like. C _2-6 alkylene group (for example, — (CH ₂ ) ₂ —, — (CH ₂ ) ₃ —, — (CH ₂ ) ₄ —, — (CH ₂ ) ₅ —, — (CH ₂ ) ₆ —, — _{CHFCH 2 -, - CHF (CH} 2) 2 -, - CHF (CH 2) 3 -, - CHF (CH 2) 4 -, - CF 2 CH 2 -, - CF 2 (CH 2) 2 -, - CF ₂ (CH ₂ ) ₃ −, −CF ₂ (CH ₂ ) ₄ −, − (CH ₂ ) ₃ CH (CH ₃ ) −, − (CH ₂ ) ₄ CH (CH ₃ ) −, − (CH ₂ ) ₃ CH (CF ₃ ) −, − (CH ₂ ) ₄ CH (CF ₃ ) −, − (CH ₃ ) CHCH ₂ −, − (CH ₃ ) CH (CH ₂ ) ₂ −, − (CH (CH ₃ )) _2- , -CH ₂ CH (OH)-, -CH ₂ CO-,-(Ph) CHCH _2-, etc.), and more preferably C _3-7 cycloalkylene or C _3-7 cycloalkylene and C _1-4 alkylene. (For example,

Etc.) is also preferable.

〔式中の記号は前記と同意義を示す。〕で表される環等が挙げられる。 Examples of the ring formed between L and Ar include 1-oxoindan-2-yl, 1-oxo-1,2,3,4-tetrahydronaphthalen-2-yl, 5-oxo-6,7, 8,9-Tetrahydro-5H-benzo [a] cyclohepten-6-yl, 2,5-dioxo-1,2,3,5,6,7-hexahydroindeno [5,6-d] imidazole-6 -Yl, 2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2,3-d] imidazol-6-yl, 2,5-dioxo-1,2,3 , 5,6,7,8,9-octahydrocyclohepta [f] benzimidazol-6-yl, 2,8-dioxo-2,3,4,6,7,8-hexahydro-1H-cyclopenta [g ] Quinazolin-7-yl, 2,9-dioxo-1,2,3,4,6,7,8,9-octahydrobenzo [g] quinazolin-8-yl, 2,10-dioxo-2,3 , 4,6,7,8,9,10-octahydro-1H-cyclohepta [g] quinazolin-9-yl, 2,2-dioxide-5-oxo-3,5,6,7-tetrahydro-1H-indeno [5,6-c] [1,2,5] thiadiazol-6-yl, 2,2-dioxide-5-oxy So-1,3,5,6,7,8-hexahydronaphtho [2,3-c] [1,2,5] thiadiazol-6-yl, 2,2-dioxide-5-oxo-3,5 , 6,7,8,9-Hexahydro-1H-cyclohepta [f] [2,1,3] benzothiadiazol-6-yl, 2,2-dioxide-8-oxo-1,3,4,6,7 , 8-Hexahydroindeno [5,6-c] [1,2,6] thiadiazin-7-yl, 2,2-dioxide-9-oxo-3,4,6,7,8,9-hexahydro -1H-naphtho [2,3-c] [1,2,6] thiadiazin-8-yl and 2,2-dioxide-10-oxo-1,3,4,6,7,8,9,10 -Octahydrocyclohepta [g] [2,1,3] benzothiadiazin-9-yl and the like. Preferably, the formula

[The symbols in the formula are as defined above. The ring etc. which are represented by these are mentioned.

〔式中、Ｒは水素原子又は置換基を有していてもよい炭化水素基を示し、Ｌ_2ａは置換基を有していてもよいＣ_1-4アルキレン基を示し、Ｘは結合手、酸素原子又は窒素原子を示し、Ａｒ₂は置換基を有していてもよい芳香環基を示すか、またはＡｒ₂とＲ、もしくはＡｒ₂とＬ_２ａとが互いに結合して環を形成していてもよい。〕で表される基等が挙げられる。
Ｒで示される「置換基を有していてもよい炭化水素基」としては、Ｒ¹で示される「置換基を有していてもよい炭化水素基」と同様のものが挙げられる。
Ｒで示される「置換基を有していてもよい炭化水素基」の「置換基」としては、Ｒ¹で示される「置換基を有していてもよい炭化水素基」の「置換基」と同様のものが挙げられ、その置換基数は１ないし３個である。
Ｌ_2ａで示される「置換基を有していてもよいＣ_1-4アルキレン基」としては、Ｌで示される「置換基を有していてもよい主鎖の原子数１ないし１０のスペーサー」において例示した、「Ｃ_1-10アルキレン基」のうち、炭素鎖数１ないし４のものが挙げられる。
Ｌ_2ａで示される「置換基を有していてもよいＣ_1-4アルキレン基」における「置換基」としては、Ｌで示される「置換基を有していてもよい主鎖の原子数１ないし１０のスペーサー」における「置換基」と同様のものが挙げられる。
Ｘで示される「結合手、酸素原子又はＮＲ^１ａ（Ｒ^１ａは水素原子、置換基を有していてもよい炭化水素基、アシル基又は置換基を有していてもよい複素環基を示す。）」におけるＲ^１ａで示される「置換基を有していてもよい炭化水素基」、「アシル基」、「置換基を有していてもよい複素環基」としては、Ｒ^１におけるそれらと同様のものが挙げられる。
Ａｒ₂で示される「置換基を有していてもよい芳香環基」の「芳香環基」としては、Ａｒで示される「縮合していてもよい５または６員芳香環基」と同様のものが挙げられる。Ａｒ₂で示される「置換基を有していてもよい芳香環基」の「置換基」としては、Ａｒで示される「縮合していてもよい５または６員芳香環基を示し、該芳香環基は置換基を有していてもよく」の「置換基」と同様のものが挙げられ、その置換基数は１ないし５個である。
Ａｒ₂とＲとが互いに結合して形成する環としては、例えば、式

〔式中、ｐ及びｑはそれぞれ１ないし３の整数を示し、Ｈ環はハロゲン、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキルおよびハロゲン化されていてもよいＣ₁₋₆アルコキシから選ばれる１ないし３個の置換基を有していてもよいベンゼン環を示す。〕で表される環等が挙げられる。
Ａｒ₂とＬ_2ａとが互いに結合して形成する環としては、例えば、式

〔式中、ｒは０ないし２の整数を、ｓは１ないし３の整数を、かつｒ＋ｓが２ないし５の整数を示し、Ｈ環は前記と同意義を示す。〕で表される環等が挙げられる。 As the “amino group optionally having substituent (s)” represented by Y, for example, the formula

[Wherein, R represents a hydrogen atom or a hydrocarbon group which may have a substituent, L _2a represents a C _1-4 alkylene group which may have a substituent, X represents a bond, Represents an oxygen atom or a nitrogen atom, Ar ₂ represents an aromatic ring group which may have a substituent, or Ar ₂ and R, or Ar ₂ and L _2a are bonded to each other to form a ring; May be. The group etc. which are represented by these are mentioned.
Examples of the “hydrocarbon group optionally having substituent (s)” represented by R include those similar to the “hydrocarbon group optionally having substituent (s)” represented by R ¹ .
The “substituent” of the “hydrocarbon group optionally having substituent (s)” represented by R is the “substituent” of the “hydrocarbon group optionally having substituent (s)” represented by R ^1. And the number of substituents is 1 to 3.
The “C _1-4 alkylene group _optionally having substituent (s)” represented by L _2a is the “spacer having 1 to 10 atoms in the main chain optionally having substituent (s)” represented by L. Among the “C _1-10 alkylene groups” exemplified in the above, those having 1 to 4 carbon chains can be mentioned.
The “substituent” in the “C _1-4 alkylene group _optionally having substituent (s)” represented by L _2a is the number of atoms of the main chain optionally having substituent (s) represented by L 1 And the same as the “substituent” in “10 to 10 spacers”.
X represents a bond, an oxygen atom or NR ^1a (where R ^1a represents a hydrogen atom, an optionally substituted hydrocarbon group, an acyl group, or an optionally substituted heterocyclic group. .) "substituent hydrocarbon group which may have a" represented by R ^1a in "," acyl group "," optionally substituted heterocyclic group ", those in R ¹ The same thing is mentioned.
Represented by Ar ₂ As the "aromatic ring group" of the "aromatic ring group optionally having substituent (s)", same as "fused or 5 or even six-membered aromatic ring group" represented by Ar Things. The “substituent” of the “optionally substituted aromatic ring group” represented by Ar ₂ represents the “optionally condensed 5- or 6-membered aromatic ring group represented by Ar, Examples of the “substituent” in the “ring group may have a substituent” include 1 to 5 substituents.
Examples of the ring formed by combining Ar ₂ and R with each other include, for example, the formula

[Wherein, p and q each represent an integer of 1 to 3, and the H ring is selected from halogen, hydroxy, optionally halogenated C _1-6 alkyl and optionally halogenated C _1-6 alkoxy. A benzene ring optionally having 1 to 3 substituents is shown. The ring etc. which are represented by these are mentioned.
Examples of the ring formed by combining Ar ₂ and L _2a with each other include, for example, the formula

[Wherein, r represents an integer of 0 to 2, s represents an integer of 1 to 3, and r + s represents an integer of 2 to 5, and the H ring has the same meaning as described above]. The ring etc. which are represented by these are mentioned.

で表される基等が挙げられる。このうち、好ましくは６員環基である。
更に好ましくは、式

で表される基である。
該「置換基を有していてもよい含窒素飽和複素環基」の「置換基」としては、上記Ｂ環で示される「置換基を有していてもよい複素環」の「置換基」と同様のものが挙げられ、その置換基数は１ないし５個である。また、該「置換基を有していてもよい含窒素飽和複素環基」の「含窒素飽和複素環基」の窒素は、式

〔式中、各記号は前記と同意義を示す。〕で表される基と同様のものを有していてもよい。 As the “nitrogen-containing saturated heterocyclic group” of the “nitrogen-containing saturated heterocyclic group optionally having substituents” represented by Y, in addition to the carbon atom and one nitrogen atom, a nitrogen atom, an oxygen atom, and Examples thereof include 5- to 9-membered (preferably 5- to 7-membered) nitrogen-containing saturated heterocyclic group which may contain 1 to 3 heteroatoms selected from sulfur atoms. Specifically, the formula

The group etc. which are represented by these are mentioned. Of these, a 6-membered cyclic group is preferable.
More preferably, the formula

It is group represented by these.
As the “substituent” of the “nitrogen-containing saturated heterocyclic group optionally having substituent (s)”, the “substituent” of the “heterocycle optionally having substituent (s)” represented by the ring B above And the number of substituents is 1 to 5. Further, the nitrogen of the “nitrogen-containing saturated heterocyclic group” in the “nitrogen-containing saturated heterocyclic group optionally having substituent (s)” has the formula

[Wherein each symbol is as defined above. ] May be the same as the group represented by

〔式中、各記号は前記と同意義を示す。〕で表される基等である。
Ｒとしては、(i)水素原子、(ii)ハロゲン原子（好ましくはフルオロ等）及びヒドロキシから選ばれる置換基を１ないし３個有していてもよいＣ_１-４アルキル基、又は(iii)Ｃ_7-16アラルキル（ベンジル等）等が好ましく、水素原子又はＣ_１-４アルキル基がより好ましい。
Ｌ_2ａとしては、ハロゲン原子、ヒドロキシ、オキソ、フェニル等から選ばれる１ないし４個の置換基を有していてもよいＣ_2−４アルキレン基（例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₂)₄−、−CHFCH₂−、−CHF(CH₂)₂−、−CHF(CH₂)₃−、−CF₂CH₂−、−CF₂(CH₂)₂−、−CF₂(CH₂)₃−、−(CH₃)CHCH₂−、−(CH₃)CH(CH₂)₂−、−(CH(CH₃))₂−、−CH₂CH(OH)−、−CH₂CO−、−(Ph)CHCH₂−等）が好ましく、ヒドロキシ、オキソ又はフェニルを有していてもよいＣ_2−３アルキレン基（例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₃)CHCH₂−、−(Ph)CHCH₂−、−CH₂CH(OH)−、−CH₂CO−等）等がより好ましく、エチレン基が最も好ましい。
Ｘとしては、結合手、酸素原子又はＮＨが好ましく、結合手がより好ましい。
Ａｒ₂として好ましくは、（1）それぞれ、ハロゲン（フルオロ、クロロ等）、Ｃ_1-6アルキル（メチル、エチル等）、ハロゲノＣ_1-6アルキル（トリフルオロメチル等）、ヒドロキシ、Ｃ_1-6アルコキシ（メトキシ、エトキシ等）、ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ、トリフルオロエトキシ等）、ニトロ、アミノ、シアノ、カルバモイル、Ｃ_1-6アルキルで置換されていてもよいカルバモイル又はホルミルで置換されていてもよいアミノ（ＮＨＣＨＯ、ＮＨＣＯＮＨ₂、ＮＨＣＯＮＨＭｅ等）、Ｃ_1-3アルキレンジオキシ（メチレンジオキシ等）、Ｃ_1-6アルキルで置換されていてもよいアミノカルボニルオキシ基（アミノカルボニルオキシ、メチルアミノカルボニルオキシ、エチルアミノカルボニルオキシ、ジメチルアミノカルボニルオキシ、ジエチルアミノカルボニルオキシ等）、５ないし７員環状アミノ−カルボニルオキシ（ (1-ピロリジニル) カルボニルオキシ、ピペリジノカルボニルオキシ等）、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル及びジ−Ｃ_1-6アルキルアミノスルホニル等から選ばれる１ないし５個（好ましくは１ないし３個）の置換基を有していてもよい、（ｉ）Ｃ_6-10アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（例えば、チエニル、フリル、ピロリル、イミダゾリル、ピラゾリル、チアゾリル、イソチアゾリル、オキサゾリル、イソオキサゾリル、ピリジル、ピラジニル、ピリミジニル、ピリダジニル、オキサジアゾリル、チアジアゾリル、フラザニル、インドリル、イソインドリル、ベンゾフラニル、キノリル、イソキノリル、ナフチリジニル、キナゾリニル、シンノリニル、アクリジニル等）、（2）Ａｒ₂とＲとが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合、または（3）Ａｒ₂とＬ₂とが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合等が挙げられる。
Ａｒ₂として、より好ましくは、それぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、（ｉ）Ｃ₆₋₁₀アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子を１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（チエニル、インドリル等）等が挙げられる。
Ｙとして、更に好ましくは、式

〔式中、各記号は前記と同意義を示す。〕で表される基等である。 Y is preferably a formula

[Wherein each symbol is as defined above. And the like.
R represents (i) a hydrogen atom, (ii) a C _1-4 alkyl group which may have 1 to 3 substituents selected from a halogen atom (preferably fluoro, etc.) and hydroxy, or (iii) C _7-16 aralkyl (such as benzyl) is preferred, and a hydrogen atom or a C _1-4 alkyl group is more preferred.
L _2a is a C _2-4 alkylene group _optionally having 1 to 4 substituents selected from a halogen atom, hydroxy, oxo, phenyl and the like (for example, — (CH ₂ ) ₂ —, — ( CH ₂ ) ₃ −, − (CH ₂ ) ₄ −, −CHFCH ₂ −, −CHF (CH ₂ ) ₂ −, −CHF (CH ₂ ) ₃ −, −CF ₂ CH ₂ −, −CF ₂ (CH ₂ ) _2- , --CF ₂ (CH ₂ ) ₃ -,-(CH ₃ ) CHCH ₂ -,-(CH ₃ ) CH (CH ₂ ) ₂ -,-(CH (CH ₃ )) _2- , --CH ₂ CH (OH) -, - CH 2 CO -, - (Ph) CHCH 2 - , etc.) are preferable, hydroxy, optionally C _2-3 alkylene group optionally having oxo or phenyl (eg, - (CH _{2) 2} -,-(CH ₂ ) ₃ -,-(CH ₃ ) CHCH ₂ -,-(Ph) CHCH _2- , -CH ₂ CH (OH)-, -CH ₂ CO-, etc.) The group is most preferred.
X is preferably a bond, an oxygen atom or NH, more preferably a bond.
Ar ₂ is preferably (1) halogen (fluoro, chloro, etc.), C _1-6 alkyl (methyl, ethyl, etc.), halogeno C _1-6 alkyl (trifluoromethyl, etc.), hydroxy, C _{1-6, respectively.} Substituted by alkoxy (methoxy, ethoxy, etc.), halogeno C _1-6 alkoxy (trifluoromethoxy, trifluoroethoxy, etc.), nitro, amino, cyano, carbamoyl, carbamoyl or formyl optionally substituted by C _1-6 alkyl Amino (NHCHO, NHCONH ₂ , NHCONHMe, etc.) optionally substituted, C _1-3 alkylenedioxy (methylenedioxy etc.), aminocarbonyloxy group (aminocarbonyloxy) optionally substituted with C _1-6 alkyl , Methylaminocarbonyloxy, ethylaminocarbonyloxy, dimethylaminocarbonyl Ruoxy, diethylaminocarbonyloxy, etc.), 5- to 7-membered cyclic amino-carbonyloxy ((1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy, etc.), aminosulfonyl, mono-C _1-6 alkylaminosulfonyl and di-C (I) a C _6-10 aryl group (such as phenyl) or (ii) optionally having 1 to 5 (preferably 1 to 3) substituents selected from _1-6 alkylaminosulfonyl and the like A 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom (which may be condensed with a benzene ring) (for example, thienyl, furyl, pyrrolyl, imidazolyl, Pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyrida Alkylsulfonyl, oxadiazolyl, thiadiazolyl, furazanyl, indolyl, isoindolyl, benzofuranyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, cinnolinyl, acridinyl, etc.), ₍₂₎ Ar 2 and and R are bonded to each other, wherein

[The symbols in the formula are as defined above. Or (3) Ar ₂ and L ₂ are bonded to each other to form a ring represented by the formula

[The symbols in the formula are as defined above. And the like.
Ar ₂ is more preferably 1 to 3 selected from halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, optionally halogenated C _1-6 alkoxy and aminosulfonyl, respectively. (I) a C _6-10 aryl group (such as phenyl) or (ii) 5 containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, 6-membered aromatic heterocyclic group (a benzene ring may be condensed) (thienyl, indolyl, etc.) and the like.
Y is more preferably a formula

[Wherein each symbol is as defined above. And the like.

〔式中の記号は前記と同意義を示す。〕で表される基（Ａ環は好ましくはアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、カルバモイルおよびモノ−又はジ−Ｃ₁₋₆アルキル−カルバモイルから選ばれる１または２個の置換基を有していてもよいベンゼン環で、Ａ'環は好ましくはアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、Ｃ₁₋₆アルキル−カルボニルアミノおよびＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有し、さらに１ないし４個の置換基（例えば、Ｃ₁₋₆アルコキシ等）を有していてもよいベンゼン環で、Ｂａ環、Ｃ”環及びＤ”環は好ましくはそれぞれＣ₁₋₆アルキル、Ｃ₁₋₆アルキル−カルボニルアミノ及びＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有していてもよく、Ｒ^１及びＲ^１'は好ましくはそれぞれ（1）水素原子、（2）それぞれヒドロキシおよびＣ₁₋₆アルコキシ−カルボニルから選ばれる１または２個の置換基を有していてもよいＣ₁₋₆アルキル基またはＣ₇₋₁₆アラルキル基（ベンジル等）または（3）式−(Ｃ＝Ｏ)−Ｒ^２'、 −(Ｃ＝Ｏ)−ＮＲ^２'Ｒ^３'または−ＳＯ_２Ｒ^２'〔式中、Ｒ^２'及びＲ^３'はそれぞれ水素原子、ハロゲン化されていてもよいＣ₁₋₆アルキルまたはＣ₆₋₁₀アリールを示す。〕で表される基）；
Ｌが（1）ハロゲン原子、ヒドロキシ、オキソ、フェニル等から選ばれる１ないし４個の置換基を有していてもよいＣ₂₋₆アルキレン基（例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₂)₄−、−(CH₂)₅−、−(CH₂)₆−、−CHFCH₂−、−CHF(CH₂)₂−、−CHF(CH₂)₃−、−CHF(CH₂)₄−、−CF₂CH₂−、−CF₂(CH₂)₂−、−CF₂(CH₂)₃−、−CF₂(CH₂)₄−、−(CH₂)₃CH(CH₃)−、−(CH₂)₄CH(CH₃)−、−(CH₂)₃CH(CF₃)−、−(CH₂)₄CH(CF₃)−、−(CH₃)CHCH₂−、−(CH₃)CH(CH₂)₂−、−(CH(CH₃))₂−、−CH₂CH(OH)−、−CH₂CO−、−(Ph)CHCH₂−など）、または（2）C_３−７シクロアルキレンまたはC_３−７シクロアルキレンとC_１−４アルキレンとの組み合わせ（例えば、

など）； As compound (I), Ar is preferably of the formula

[The symbols in the formula are as defined above. The ring A is preferably one or two selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. In the optionally substituted benzene ring, the A ′ ring is preferably aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonyl A benzene ring having 1 or 2 substituents selected from amino and further having 1 to 4 substituents (for example, C _1-6 alkoxy, etc.), Ba ring, C ″ ring And D ″ rings preferably have 1 or 2 substituents each selected from C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. R ¹ and R ^{1 ′} may preferably have 1 or 2 substituents each selected from (1) a hydrogen atom, and (2) hydroxy and C _1-6 alkoxy-carbonyl, respectively. _1-6 alkyl group or C _7-16 aralkyl group (benzyl etc.) or (3) Formula — (C═O) —R ^{2 ′} , — (C═O) —NR ^{2 ′} R ^{3 ′} or —SO ₂ R ^{2 ′} [wherein R ^{2 ′} and R ^{3 ′} each represent a hydrogen atom, optionally halogenated C _1-6 alkyl or C _6-10 aryl];
L is (1) a C _2-6 alkylene group (for example, — (CH ₂ ) ₂ —, — ((1)) optionally having 1 to 4 substituents selected from a halogen atom, hydroxy, oxo, phenyl and the like. CH ₂ ) ₃ −, − (CH ₂ ) ₄ −, − (CH ₂ ) ₅ −, − (CH ₂ ) ₆ −, −CHFCH ₂ −, −CHF (CH ₂ ) ₂ −, −CHF (CH ₂ ) ₃ −, −CHF (CH ₂ ) ₄ −, −CF ₂ CH ₂ −, −CF ₂ (CH ₂ ) ₂ −, −CF ₂ (CH ₂ ) ₃ −, −CF ₂ (CH ₂ ) ₄ −, − (CH ₂ ) ₃ CH (CH ₃ ) −, − (CH ₂ ) ₄ CH (CH ₃ ) −, − (CH ₂ ) ₃ CH (CF ₃ ) −, − (CH ₂ ) ₄ CH (CF ₃ ) − ,-(CH ₃ ) CHCH ₂ -,-(CH ₃ ) CH (CH ₂ ) ₂ -,-(CH (CH ₃ )) _2- , -CH ₂ CH (OH)-, -CH ₂ CO-,- (Ph) CHCH ₂ — and the like), or (2) C _3-7 cycloalkylene or a combination of C _3-7 cycloalkylene and C _1-4 alkylene (eg,

Such);

〔式中、各記号は前記と同意義を示す。〕で表される基で、
Ｒが(i)水素原子、(ii)ハロゲン原子（好ましくはフルオロ等）及びヒドロキシから選ばれる置換基を１ないし３個有していてもよいＣ_１-４アルキル基、又は(iii)Ｃ_7-16アラルキル（ベンジル等）等；
Ｌ_2ａがハロゲン原子、ヒドロキシ、オキソ、フェニル等から選ばれる１ないし４個の置換基を有していてもよいＣ_2−４アルキレン基（例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₂)₄−、−CHFCH₂−、−CHF(CH₂)₂−、−CHF(CH₂)₃−、−CF₂CH₂−、−CF₂(CH₂)₂−、−CF₂(CH₂)₃−、−(CH₃)CHCH₂−、−(CH₃)CH(CH₂)₂−、−(CH(CH₃))₂−、−CH₂CH(OH)−、−CH₂CO−、−(Ph)CHCH₂−等）；
Ｘが結合手、酸素原子又はＮＨ；
Ａｒ₂が（1）それぞれ、ハロゲン（フルオロ、クロロ等）、Ｃ_1-6アルキル（メチル、エチル等）、ハロゲノＣ_1-6アルキル（トリフルオロメチル等）、ヒドロキシ、Ｃ_1-6アルコキシ（メトキシ、エトキシ等）、ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ、トリフルオロエトキシ等）、ニトロ、アミノ、シアノ、カルバモイル、Ｃ_1-6アルキルで置換されていてもよいカルバモイル又はホルミルで置換されていてもよいアミノ（ＮＨＣＨＯ、ＮＨＣＯＮＨ₂、ＮＨＣＯＮＨＭｅ等）、Ｃ_1-3アルキレンジオキシ（メチレンジオキシ等）、Ｃ_1-6アルキルで置換されていてもよいアミノカルボニルオキシ基（アミノカルボニルオキシ、メチルアミノカルボニルオキシ、エチルアミノカルボニルオキシ、ジメチルアミノカルボニルオキシ、ジエチルアミノカルボニルオキシ等）、５ないし７員環状アミノ−カルボニルオキシ（ (1-ピロリジニル) カルボニルオキシ、ピペリジノカルボニルオキシ等）、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル及びジ−Ｃ_1-6アルキルアミノスルホニル等から選ばれる１ないし５個（好ましくは１ないし３個）の置換基を有していてもよい、（ｉ）Ｃ_6-10アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（例えば、チエニル、フリル、ピロリル、イミダゾリル、ピラゾリル、チアゾリル、イソチアゾリル、オキサゾリル、イソオキサゾリル、ピリジル、ピラジニル、ピリミジニル、ピリダジニル、オキサジアゾリル、チアジアゾリル、フラザニル、インドリル、イソインドリル、ベンゾフラニル、キノリル、イソキノリル、ナフチリジニル、キナゾリニル、シンノリニル、アクリジニル等）、（2）Ａｒ₂とＲとが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合、または（3）Ａｒ₂とＬ₂とが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合
である化合物等が挙げられる。 Y is the formula

[Wherein each symbol is as defined above. In the group represented by
R is a C _1-4 alkyl group _optionally having 1 to 3 substituents selected from (i) a hydrogen atom, (ii) a halogen atom (preferably fluoro, etc.) and hydroxy, or (iii) C _{7 -16} aralkyl (benzyl etc.) etc .;
L _2a is a C _2-4 alkylene group (for example, — (CH ₂ ) ₂ —, — (CH ₂ ) _optionally having 1 to 4 substituents selected from a halogen atom, hydroxy, oxo, phenyl and the like. ) ₃ −, − (CH ₂ ) ₄ −, −CHFCH ₂ −, −CHF (CH ₂ ) ₂ −, −CHF (CH ₂ ) ₃ −, −CF ₂ CH ₂ −, −CF ₂ (CH ₂ ) ₂ -, --CF ₂ (CH ₂ ) ₃ -,-(CH ₃ ) CHCH ₂ -,-(CH ₃ ) CH (CH ₂ ) ₂ -,-(CH (CH ₃ )) _2- , --CH ₂ CH ( _{OH) -, - CH 2 CO} -, - (Ph) CHCH 2 - , etc.);
X is a bond, an oxygen atom or NH;
Ar ₂ is (1) halogen (fluoro, chloro, etc.), C _1-6 alkyl (methyl, ethyl, etc.), halogeno C _1-6 alkyl (trifluoromethyl, etc.), hydroxy, C _1-6 alkoxy (methoxy), respectively. , Ethoxy, etc.), halogeno C _1-6 alkoxy (trifluoromethoxy, trifluoroethoxy, etc.), nitro, amino, cyano, carbamoyl, substituted with carbamoyl or formyl optionally substituted with C _1-6 alkyl Amino (NHCHO, NHCONH ₂ , NHCONHMe, etc.), C _1-3 alkylenedioxy (methylenedioxy, etc.), aminocarbonyloxy group (aminocarbonyloxy, methylamino) optionally substituted by C _1-6 alkyl Carbonyloxy, ethylaminocarbonyloxy, dimethylaminocarbonyloxy, diethyl ), 5- to 7-membered cyclic amino-carbonyloxy ((1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy etc.), aminosulfonyl, mono-C _1-6 alkylaminosulfonyl and di-C ₁ (I) a C _6-10 aryl group (such as phenyl) or (ii) nitrogen which may have 1 to 5 (preferably 1 to 3) substituents selected from _-6 alkylaminosulfonyl and the like 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from an atom, oxygen atom and sulfur atom (which may be condensed with a benzene ring) (for example, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl) , Thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxadi Zoriru, thiadiazolyl, furazanyl, indolyl, isoindolyl, benzofuranyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, cinnolinyl, acridinyl, etc.), (2) Ar ₂ and the R are bonded to each other, wherein

[The symbols in the formula are as defined above. Or (3) Ar ₂ and L ₂ are bonded to each other to form a ring represented by the formula

[The symbols in the formula are as defined above. ] The compound etc. which are the cases where the ring represented by these are formed are mentioned.

〔式中、Ａｒ₁は置換基を有していてもよい二環ないし四環式縮合ベンゼン環基を示し、Ｌ₁は置換基を有していてもよいＣ_4-6アルキレン基を示し、その他の各記号は前記と同意義を示す。〕で表される化合物（以下、化合物（Ｉa）と略記することもある）又はその塩は新規化合物である。
Ａｒ₁で示される「置換基を有していてもよい二環ないし四環式縮合ベンゼン環基」の「二環ないし四環式縮合ベンゼン環基」としては、Ａｒで示される「縮合していてもよい５または６員芳香環基」の「５または６員芳香環基」が「フェニル基」の場合、該「フェニル基」が縮合する例として挙げた縮合ベンゼン環基と同様のものが挙げられる。
Ａｒ₁で示される「置換基を有していてもよい二環ないし四環式縮合ベンゼン環基」の「置換基」としては、Ａｒで示される「縮合していてもよい５または６員芳香環基を示し、該芳香環基は置換基を有していてもよく」の「置換基」として挙げた置換基と同様のものが挙げられる。
Ａｒ₁として、好ましくは、式

〔式中の各記号は前記と同意義を示す。〕で表される基等が挙げられる。 In addition, among the compounds (I), the formula

Wherein, Ar ₁ represents a two may have a substituent ring or tetracyclic condensed benzene ring group, L ₁ represents an optionally C _4-6 alkylene group which may have a substituent, Other symbols are as defined above. ] (Hereinafter also abbreviated as compound (Ia)) or a salt thereof is a novel compound.
The "bicyclic or tetracyclic condensed benzene ring group" of the "optionally two may be ring or tetracyclic condensed benzene ring group having a substituent" represented by Ar _1, are combined "condensed represented by Ar When the “5- or 6-membered aromatic ring group” of the “optional 5- or 6-membered aromatic ring group” is a “phenyl group”, the same condensed benzene ring group as mentioned as an example in which the “phenyl group” is condensed is Can be mentioned.
Represented by Ar ₁ as the "substituent" of the "two may have a substituent ring or tetracyclic condensed benzene ring group", "fused may be 5 or 6 membered aromatic represented by Ar Examples thereof are the same as the substituents exemplified as the “substituent” in “A ring group, the aromatic ring group may have a substituent”.
Ar ₁ is preferably of the formula

[Each symbol in the formula is as defined above. The group etc. which are represented by these are mentioned.

〔式中の記号は前記と同意義を示す。〕で表される基等が挙げられる。
ここで、Ａ環としては、(i)ハロゲン（フルオロ等）、(ii)Ｃ_1-6アルコキシ（メトキシ等）、(iii)ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ等）、(iv)アミノ、(v)（モノ又はジ）Ｃ_1-6アルキルアミノ（メチルアミノ、エチルアミノ、ジメチルアミノ、ジエチルアミノ等）、(vi)1-ピロリジニル、(vii)ピペリジノ、(viii)1-ピペラジニル、(ix)Ｎ−メチル-1-ピペラジニル、(x)Ｎ−アセチル-1-ピペラジニル、(xi)モルホリノ、(xii)ヘキサメチレンイミノ、(xiii)イミダゾリル、(xiv)Ｃ_1-6アルキル（メチル等）でエステル化されていてもよいカルボキシで置換されていてもよいＣ_1-6アルキル（プロピル等）、（xv）低級アルキル−カルボニルアミノ（アセチルアミノ等）、（xvi）低級アルキルスルホニルアミノ（メチルスルホニルアミノ等）,（xvii）アミノスルホニル、(xviii) （モノ又はジ）Ｃ_1-6アルキルアミノスルホニル、(xix)５ないし７員環状アミノ−スルホニル（ (1-ピロリジニル) スルホニル、ピペリジノスルホニル、(1-ピペラジニル) スルホニル、モルホリノスルホニル等）（xx）カルバモイル、(xxi) （モノ又はジ）Ｃ_1-6アルキルカルバモイル、(xxi)５ないし７員環状アミノ−カルボニル（ (1-ピロリジニル) カルボニル、ピペリジノカルボニル、(1-ピペラジニル) カルボニル、モルホリノカルボニル等）、(xxii)シアノ等から選ばれる１ないし４個の置換基を有していてもよいベンゼン環が好ましい。より好ましくはＡ環がアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、カルバモイルおよびモノ−又はジ−Ｃ₁₋₆アルキル−カルバモイルから選ばれる１または２個の置換基を有していてもよいベンゼン環である。
また、Ｂａ環、Ｃ”環及びＤ”環はそれぞれＣ₁₋₆アルキル、Ｃ₁₋₆アルキル−カルボニルアミノ及びＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有していてもよく、Ｒ^１及びＲ^１'はそれぞれ（1）水素原子、（2）それぞれヒドロキシおよびＣ₁₋₆アルコキシ−カルボニルから選ばれる１または２個の置換基を有していてもよいＣ₁₋₆アルキル基またはＣ₇₋₁₆アラルキル基または（3）式−(Ｃ＝Ｏ)−Ｒ^２'、 −(Ｃ＝Ｏ)−ＮＲ^２'Ｒ^３'もしくは−ＳＯ_２Ｒ^２'〔式中、Ｒ^２'及びＲ^３'はそれぞれ水素原子、ハロゲン化されていてもよいＣ₁₋₆アルキルまたはＣ₆₋₁₀アリールを示す。〕で表される基であるものが好ましい。 As Ar ₁ , more preferably, for example, the formula

[The symbols in the formula are as defined above. The group etc. which are represented by these are mentioned.
Here, the A ring includes (i) halogen (such as fluoro), (ii) C _1-6 alkoxy (such as methoxy), (iii) halogeno C _1-6 alkoxy (such as trifluoromethoxy), (iv) amino (Vi) (mono or di) C _1-6 alkylamino (methylamino, ethylamino, dimethylamino, diethylamino, etc.), (vi) 1-pyrrolidinyl, (vii) piperidino, (viii) 1-piperazinyl, (ix ) N-methyl-1-piperazinyl, (x) N-acetyl-1-piperazinyl, (xi) morpholino, (xii) hexamethyleneimino, (xiii) imidazolyl, (xiv) C _1-6 alkyl (methyl etc.) C _1-6 alkyl (propyl etc.) optionally substituted with carboxy which may be esterified, (xv) lower alkyl-carbonylamino (acetylamino etc.), (xvi) lower alkylsulfonylamino (methylsulfonylamino) Etc.), (xvii) amino Ruhoniru, (xviii) (mono or di) C _1-6 alkylaminosulfonyl, (xix) 5 to 7-membered cyclic amino - sulfonyl ((1-pyrrolidinyl) sulfonyl, piperidinosulfonyl, (1-piperazinyl) sulfonyl, morpholino Sulfonyl etc.) (xx) carbamoyl, (xxi) (mono or di) C _1-6 alkylcarbamoyl, (xxi) 5- to 7-membered cyclic amino-carbonyl ((1-pyrrolidinyl) carbonyl, piperidinocarbonyl, (1- (Piperazinyl) carbonyl, morpholinocarbonyl, etc.), (xxii) a benzene ring optionally having 1 to 4 substituents selected from cyano and the like is preferable. More preferably, the A ring has 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. It may be a benzene ring.
In addition, the Ba ring, C ″ ring and D ″ ring each have 1 or 2 substituents selected from C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. at best, R ¹ and R ^{1 'are} each (1) a hydrogen atom, (2), respectively hydroxy and C _1-6 alkoxy - which may have 1 or 2 substituents selected from carbonyl C _{1 -6} alkyl group or C _7-16 aralkyl group or (3) _Formula- (C = O) -R ^{2 '} ,-(C = O) -NR ^2' R ^{3 '} or -SO ₂ R ^2' , R ^{2 ′} and R ^{3 ′} each represent a hydrogen atom, an optionally halogenated C _1-6 alkyl or C _6-10 aryl. ] Which is group represented by these is preferable.

Represented by L ₁ As the "C _4-6 alkylene group which may have a substituent", "of from 10 main chain atoms of C 1 which may have a substituent spacer" represented by L Among the “C _1-10 alkylene groups” exemplified in the above, those having 4 to 6 carbon chains can be mentioned.
As "substituent" of the "optionally substituted C _4-6 alkylene group" represented by L _1, atoms of "may have a substituent main chain represented by L 1 And the same as the “substituent” in “10 to 10 spacers”. Preferable examples include 1 to 4 substituents selected from, for example, a halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), nitro, cyano, optionally halogenated C _1-6 alkoxy, hydroxy and the like. It is done.
Preferred as L _1, for _{example, - (CH 2) 4 -} , - (CH 2) 5 -, - (CH 2) 6 -, - CHF (CH 2) 3 -, - CHF (CH 2) 4 -, _{-CF 2 (CH 2) 3 -} , - CF 2 (CH 2) 4 -, - (CH 2) 3 CH (CH 3) -, - (CH 2) 4 CH (CH 3) -, - (CH 2 ) ₃ CH (CF ₃ ) —, — (CH ₂ ) ₄ CH (CF ₃ ) — and the like.

〔式中の記号は前記と同意義を示す。〕で表される基（より好ましくは、

〔式中の記号は前記と同意義を示す。〕で表される基）（Ａ環は好ましくはアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、カルバモイルおよびモノ−又はジ−Ｃ₁₋₆アルキル−カルバモイルから選ばれる１または２個の置換基を有していてもよいベンゼン環で、Ｂａ環、Ｃ”環及びＤ”環は好ましくはそれぞれＣ₁₋₆アルキル、Ｃ₁₋₆アルキル−カルボニルアミノ及びＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有していてもよく、Ｒ^１及びＲ^１'は好ましくはそれぞれ（1）水素原子、（2）それぞれヒドロキシおよびＣ₁₋₆アルコキシ−カルボニルから選ばれる１または２個の置換基を有していてもよいＣ₁₋₆アルキル基またはＣ₇₋₁₆アラルキル基（ベンジル等）または（3）式−(Ｃ＝Ｏ)−Ｒ^２'、 −(Ｃ＝Ｏ)−ＮＲ^２'Ｒ^３'または−ＳＯ_２Ｒ^２'〔式中、Ｒ^２'及びＲ^３'はそれぞれ水素原子、ハロゲン化されていてもよいＣ₁₋₆アルキルまたはＣ₆₋₁₀アリールを示す。〕で表される基）；
Ｌ₁が−(CH₂)₄−、−(CH₂)₅−、−CHF(CH₂)₃−、−CHF(CH₂)₄−、−CF₂(CH₂)₃−、−CF₂(CH₂)₄−、−(CH₂)₃CH(CH₃)−、−(CH₂)₄CH(CH₃)−等の１または２個のハロゲン原子を有していてもよいＣ₄₋₅アルキレン基（好ましくは無置換Ｃ₄₋₅アルキレン基）；
Ｒが (i)水素原子、(ii)ハロゲン原子（好ましくはフルオロ等）及びヒドロキシから選ばれる置換基を１ないし３個有していてもよいＣ_１-４アルキル基、又は(iii)Ｃ_7-16アラルキル（ベンジル等）等（より好ましくは水素原子またはＣ_１-４アルキル基）；
Ｌ₂がハロゲン原子、ヒドロキシ、オキソ、フェニル等から選ばれる１ないし４個の置換基を有していてもよいＣ_2−４アルキレン基（例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₂)₄−、−CHFCH₂−、−CHF(CH₂)₂−、−CHF(CH₂)₃−、−CF₂CH₂−、−CF₂(CH₂)₂−、−CF₂(CH₂)₃−、−(CH₃)CHCH₂−、−(CH₃)CH(CH₂)₂−、−(CH(CH₃))₂−、−CH₂CH(OH)−、−CH₂CO−、−(Ph)CHCH₂−等）（より好ましくはヒドロキシ、オキソまたはフェニルを有していてもよいＣ_2−３アルキレン基）；
Ｘが結合手、酸素原子又はＮＨ（より好ましくは結合手）；
Ａｒ₂が（1）それぞれ、ハロゲン（フルオロ、クロロ等）、Ｃ_1-6アルキル（メチル、エチル等）、ハロゲノＣ_1-6アルキル（トリフルオロメチル等）、ヒドロキシ、Ｃ_1-6アルコキシ（メトキシ、エトキシ等）、ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ、トリフルオロエトキシ等）、ニトロ、アミノ、シアノ、カルバモイル、Ｃ_1-6アルキルで置換されていてもよいカルバモイル又はホルミルで置換されていてもよいアミノ（ＮＨＣＨＯ、ＮＨＣＯＮＨ₂、ＮＨＣＯＮＨＭｅ等）、Ｃ_1-3アルキレンジオキシ（メチレンジオキシ等）、Ｃ_1-6アルキルで置換されていてもよいアミノカルボニルオキシ基（アミノカルボニルオキシ、メチルアミノカルボニルオキシ、エチルアミノカルボニルオキシ、ジメチルアミノカルボニルオキシ、ジエチルアミノカルボニルオキシ等）、５ないし７員環状アミノ−カルボニルオキシ（ (1-ピロリジニル) カルボニルオキシ、ピペリジノカルボニルオキシ等）、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル及びジ−Ｃ_1-6アルキルアミノスルホニル等から選ばれる１ないし５個（好ましくは１ないし３個）の置換基を有していてもよい、（ｉ）Ｃ_6-10アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（例えば、チエニル、フリル、ピロリル、イミダゾリル、ピラゾリル、チアゾリル、イソチアゾリル、オキサゾリル、イソオキサゾリル、ピリジル、ピラジニル、ピリミジニル、ピリダジニル、オキサジアゾリル、チアジアゾリル、フラザニル、インドリル、イソインドリル、ベンゾフラニル、キノリル、イソキノリル、ナフチリジニル、キナゾリニル、シンノリニル、アクリジニル等）、（2）Ａｒ₂とＲとが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合、または（3）Ａｒ₂とＬ₂とが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合（Ａｒ_２はより好ましくは、それぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、（ｉ）Ｃ₆₋₁₀アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子を１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（チエニル、インドリル等）等である。）
である化合物等が挙げられる。 As compound (Ia), preferably Ar ₁ is of the formula

[The symbols in the formula are as defined above. A group represented by (more preferably,

[The symbols in the formula are as defined above. A ring is preferably one or two selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. In the optionally substituted benzene ring, the Ba ring, C ″ ring and D ″ ring are preferably C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino, respectively. And R ¹ and R ^{1 ′} are preferably each selected from (1) a hydrogen atom, (2) hydroxy and C _1-6 alkoxy-carbonyl, respectively. An optionally substituted C _1-6 alkyl group or C _7-16 aralkyl group (such as benzyl) or (3) a formula — (C═O) —R ^{2 ′} , — (C = O) -NR ^{2 '} R ^{3 'Or} _-SO 2 R ^2' wherein, R ^{2 'and} R ^3' are each a hydrogen atom, a optionally halogenated C _1-6 alkyl or C _6-10 aryl.] Represented by Group);
L ₁ is _{- (CH 2) 4 -,} - (CH 2) 5 -, - CHF (CH 2) 3 -, - CHF (CH 2) 4 -, - CF 2 (CH 2) 3 -, - CF 2 C ₄ which may have one or two halogen atoms such as (CH ₂ ) ₄ -,-(CH ₂ ) ₃ CH (CH ₃ )-,-(CH ₂ ) ₄ CH (CH ₃ )- _{A -5} alkylene group (preferably an unsubstituted C _4-5 alkylene group);
R is (i) a hydrogen atom, (ii) a halogen atom (preferably fluoro, etc.) 1 substituent to 3 substituents optionally having C _1-4 alkyl group selected from and hydroxy, or (iii) C _{7 -16} aralkyl (such as benzyl) and the like (more preferably a hydrogen atom or a C _1-4 alkyl group);
L ₂ is a C _2-4 alkylene group (for example, — (CH ₂ ) ₂ —, — (CH ₂ ) which may have 1 to 4 substituents selected from a halogen atom, hydroxy, oxo, phenyl and the like. ) ₃ −, − (CH ₂ ) ₄ −, −CHFCH ₂ −, −CHF (CH ₂ ) ₂ −, −CHF (CH ₂ ) ₃ −, −CF ₂ CH ₂ −, −CF ₂ (CH ₂ ) ₂ -, --CF ₂ (CH ₂ ) ₃ -,-(CH ₃ ) CHCH ₂ -,-(CH ₃ ) CH (CH ₂ ) ₂ -,-(CH (CH ₃ )) _2- , --CH ₂ CH ( _{OH) -, - CH 2 CO} -, - (Ph) CHCH 2 - , etc.) (more preferably hydroxy, optionally C _2-3 alkylene group optionally having oxo or phenyl);
X is a bond, an oxygen atom or NH (more preferably a bond);
Ar ₂ is (1) halogen (fluoro, chloro, etc.), C _1-6 alkyl (methyl, ethyl, etc.), halogeno C _1-6 alkyl (trifluoromethyl, etc.), hydroxy, C _1-6 alkoxy (methoxy), respectively. , Ethoxy, etc.), halogeno C _1-6 alkoxy (trifluoromethoxy, trifluoroethoxy, etc.), nitro, amino, cyano, carbamoyl, substituted with carbamoyl or formyl optionally substituted with C _1-6 alkyl Amino (NHCHO, NHCONH ₂ , NHCONHMe, etc.), C _1-3 alkylenedioxy (methylenedioxy, etc.), aminocarbonyloxy group (aminocarbonyloxy, methylamino) optionally substituted by C _1-6 alkyl Carbonyloxy, ethylaminocarbonyloxy, dimethylaminocarbonyloxy, diethyl ), 5- to 7-membered cyclic amino-carbonyloxy ((1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy etc.), aminosulfonyl, mono-C _1-6 alkylaminosulfonyl and di-C ₁ (I) a C _6-10 aryl group (such as phenyl) or (ii) nitrogen which may have 1 to 5 (preferably 1 to 3) substituents selected from _-6 alkylaminosulfonyl and the like 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from an atom, oxygen atom and sulfur atom (which may be condensed with a benzene ring) (for example, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl) , Thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxadi Zoriru, thiadiazolyl, furazanyl, indolyl, isoindolyl, benzofuranyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, cinnolinyl, acridinyl, etc.), (2) Ar ₂ and the R are bonded to each other, wherein

[The symbols in the formula are as defined above. Or (3) Ar ₂ and L ₂ are bonded to each other to form a ring represented by the formula

[The symbols in the formula are as defined above. (Ar ₂ is more preferably halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, and optionally halogenated C _1-6 alkoxy, respectively. And (i) a C _6-10 aryl group (such as phenyl) or (ii) a hetero atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, which may have 1 to 3 substituents selected from aminosulfonyl And a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 atoms (a benzene ring may be condensed) (thienyl, indolyl, etc.).
The compound etc. which are are mentioned.

〔式中、Ａｒ₃はそれぞれ置換基を有していてもよいベンズイミダゾール環基、キナゾリン環基、1,4-ベンズオキサジン環基または三環ないし四環式縮合ベンゼン環基を示し、Ｌ₃は置換基を有していてもよいＣ_2-4アルキレン基を示し、その他の各記号は前記と同意義を示す。〕で表される化合物（以下、化合物（Ｉb）と略記することもある）又はその塩は新規化合物である。
Ａｒ₃で示される「置換基を有していてもよい三環ないし四環式縮合ベンゼン環基」の「三環ないし四環式縮合ベンゼン環基」としては、Ａｒで示される「縮合していてもよい５または６員芳香環基」の「５または６員芳香環基」が「フェニル基」の場合、該「フェニル基」が縮合する例として挙げた縮合ベンゼン環基と同様のものが挙げられる。
Ａｒ₃で示される「それぞれ置換基を有していてもよいベンズイミダゾール環基、キナゾリン環基、1,4-ベンズオキサジン環基または三環ないし四環式縮合ベンゼン環基」の「置換基」としては、Ａｒで示される「縮合していてもよい５または６員芳香環基を示し、該芳香環基は置換基を有していてもよく」の「置換基」として挙げた置換基と同様のものが挙げられる。
Ｌ₃で示される「置換基を有していてもよいＣ_2-4アルキレン基」としては、Ｌで示される「置換基を有していてもよい主鎖の原子数１ないし１０のスペーサー」において例示した、「Ｃ_1-10アルキレン基」のうち、炭素鎖数２ないし４のものが挙げられる。
Ｌ₃で示される「置換基を有していてもよいＣ_2-4アルキレン基」における「置換基」としては、Ｌで示される「置換基を有していてもよい主鎖の原子数１ないし１０のスペーサー」における「置換基」と同様のものが挙げられる。好ましくは、例えばハロゲン原子(例、フッ素、塩素、臭素、ヨウ素など)、ニトロ、シアノ、ハロゲン化されていてもよいC_1-6アルコキシ、ヒドロキシなどから選ばれる１ないし４個の置換基が挙げられる。
Ｌ₃として好ましくは、例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₂)₄−、−CHFCH₂−、−CHF(CH₂)₂−、−CF₂CH₂−、−CF₂(CH₂)₂−などの１または２個のハロゲン原子を有していてもよいＣ₂₋₄アルキレン基などが挙げられる。
化合物（Ｉｂ）として、好ましくは、Ａｒ₃が式

〔式中の各記号は前記と同意義を示す。〕で表される基（このうち、Ａ環は無置換で、Ｃ'環及びＤ'環は式中のオキソ基以外に置換基を有さない場合がそれぞれ好ましい）；
Ｌ₃が−(CH₂)₂−、−(CH₂)₃−、−CHFCH₂−、−CHF(CH₂)₂−、−CF₂CH₂−、−CF₂(CH₂)₂−等の１または２個のハロゲン原子を有していてもよいＣ₂₋₃アルキレン基（より好ましくはエチレン基）；
Ｌ₂が−(CH₂)₂−、−(CH₂)₃−、−CF₂CH₂−、−CF₂(CH₂)₂−、−(CH₃)CHCH₂−、又は−(CH₃)CH(CH₂)₂−、−CH₂CH(OH)−、−CH₂CO−、−(Ph)CHCH₂−等のハロゲン原子、ヒドロキシ、オキソ、フェニル等から選ばれる１ないし４個の置換基を有していてもよいＣ₂₋₄アルキレン基（より好ましくはヒドロキシ、オキソまたはフェニルを有していてもよいＣ₂₋₃アルキレン基）；
Ｘが結合手、酸素原子又はＮＨ（より好ましくは結合手又は酸素原子）；
Ａｒ₂が（1）それぞれ、ハロゲン（フルオロ、クロロ等）、Ｃ_1-6アルキル（メチル、エチル等）、ハロゲノＣ_1-6アルキル（トリフルオロメチル等）、ヒドロキシ、Ｃ_1-6アルコキシ（メトキシ、エトキシ等）、ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ、トリフルオロエトキシ等）、ニトロ、アミノ、シアノ、カルバモイル、Ｃ_1-6アルキルで置換されていてもよいカルバモイル又はホルミルで置換されていてもよいアミノ（ＮＨＣＨＯ、ＮＨＣＯＮＨ₂、ＮＨＣＯＮＨＭｅ等）、Ｃ_1-3アルキレンジオキシ（メチレンジオキシ等）、Ｃ_1-6アルキルで置換されていてもよいアミノカルボニルオキシ基（アミノカルボニルオキシ、メチルアミノカルボニルオキシ、エチルアミノカルボニルオキシ、ジメチルアミノカルボニルオキシ、ジエチルアミノカルボニルオキシ等）、５ないし７員環状アミノ−カルボニルオキシ（ (1-ピロリジニル) カルボニルオキシ、ピペリジノカルボニルオキシ等）、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル及びジ−Ｃ_1-6アルキルアミノスルホニル等から選ばれる１ないし５個（好ましくは１ないし３個）の置換基を有していてもよい、（ｉ）Ｃ_6-10アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（例えば、チエニル、フリル、ピロリル、イミダゾリル、ピラゾリル、チアゾリル、イソチアゾリル、オキサゾリル、イソオキサゾリル、ピリジル、ピラジニル、ピリミジニル、ピリダジニル、オキサジアゾリル、チアジアゾリル、フラザニル、インドリル、イソインドリル、ベンゾフラニル、キノリル、イソキノリル、ナフチリジニル、キナゾリニル、シンノリニル、アクリジニル等）（より好ましくは、それぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、（ｉ）Ｃ₆₋₁₀アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（チエニル、インドリル等）等である。）、または（2）Ａｒ₂とＬ₂とが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合
である化合物等が挙げられる。 In addition, among the compounds (I), the formula

Wherein, Ar ₃ good benzimidazole ring group which may have a substituent, respectively, a quinazoline ring group, a 1,4-benzoxazine ring group or a tricyclic or tetracyclic condensed benzene ring group, L _{3 Represents a} C _2-4 alkylene group which may have a substituent, and other symbols are as defined above. ] (Hereinafter also abbreviated as compound (Ib)) or a salt thereof is a novel compound.
As "tricyclic or tetracyclic condensed benzene ring group" of the "three may be substituted ring or tetracyclic condensed benzene ring group" represented by Ar _3, have combined "condensed represented by Ar When the “5- or 6-membered aromatic ring group” of the “optional 5- or 6-membered aromatic ring group” is a “phenyl group”, the same condensed benzene ring group as mentioned as an example in which the “phenyl group” is condensed is Can be mentioned.
“Substituent” of “benzimidazole ring group, quinazoline ring group, 1,4-benzoxazine ring group, or tricyclic to tetracyclic condensed benzene ring group each optionally having a substituent” represented by Ar ₃ And the substituents listed as the “substituent” of “showing an optionally condensed 5- or 6-membered aromatic ring group, which may have a substituent” represented by Ar; The same thing is mentioned.
Represented by L ₃ As the "C _2-4 alkylene group which may have a substituent", "of from 10 main chain atoms of C 1 which may have a substituent spacer" represented by L Among the “C _1-10 alkylene group” exemplified in the above, those having 2 to 4 carbon chains can be mentioned.
As "substituent" of the "optionally substituted C _2-4 alkylene group" represented by L _3, several atomic "in the main may be substituted chains represented by L 1 And the same as the “substituent” in “10 to 10 spacers”. Preferable examples include 1 to 4 substituents selected from, for example, a halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), nitro, cyano, optionally halogenated C _1-6 alkoxy, hydroxy and the like. It is done.
The preferred L _3, for _{example, - (CH 2) 2 -} , - (CH 2) 3 -, - (CH 2) 4 -, - CHFCH 2 -, - CHF (CH 2) 2 -, - CF 2 CH _{2 -, - CF 2 (CH} 2) 2 - and the like one or two good C _2-4 alkylene group optionally having a halogen atom such as.
As compound (Ib), Ar ₃ preferably has the formula

[Each symbol in the formula is as defined above. A group represented by the formula (of which A ring is unsubstituted, and C ′ ring and D ′ ring each preferably have no substituent other than oxo group in the formula);
L ₃ is _{- (CH 2) 2 -,} - (CH 2) 3 -, - CHFCH 2 -, - CHF (CH 2) 2 -, - CF 2 CH 2 -, - CF 2 (CH 2) 2 - , etc. A C _2-3 alkylene group (more preferably an ethylene group) optionally having 1 or 2 halogen atoms;
L ₂ is-(CH ₂ ) ₂ -,-(CH ₂ ) _3- , -CF ₂ CH _2- , -CF ₂ (CH ₂ ) ₂ -,-(CH ₃ ) CHCH _2- , or-(CH ₃ ) CH (CH ₂ ) ₂ —, —CH ₂ CH (OH) —, —CH ₂ CO—, — (Ph) CHCH ₂ — and the like, 1 to 4 selected from halogen, hydroxy, oxo, phenyl, etc. which may have a substituent C _2-4 alkylene group (more preferably a hydroxy, oxo or optionally C _2-3 alkylene group which may have a phenyl);
X is a bond, an oxygen atom or NH (more preferably a bond or an oxygen atom);
Ar ₂ is (1) halogen (fluoro, chloro, etc.), C _1-6 alkyl (methyl, ethyl, etc.), halogeno C _1-6 alkyl (trifluoromethyl, etc.), hydroxy, C _1-6 alkoxy (methoxy), respectively. , Ethoxy, etc.), halogeno C _1-6 alkoxy (trifluoromethoxy, trifluoroethoxy, etc.), nitro, amino, cyano, carbamoyl, substituted with carbamoyl or formyl optionally substituted with C _1-6 alkyl Amino (NHCHO, NHCONH ₂ , NHCONHMe, etc.), C _1-3 alkylenedioxy (methylenedioxy, etc.), aminocarbonyloxy group (aminocarbonyloxy, methylamino) optionally substituted by C _1-6 alkyl Carbonyloxy, ethylaminocarbonyloxy, dimethylaminocarbonyloxy, diethyl ), 5- to 7-membered cyclic amino-carbonyloxy ((1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy etc.), aminosulfonyl, mono-C _1-6 alkylaminosulfonyl and di-C ₁ (I) a C _6-10 aryl group (such as phenyl) or (ii) nitrogen which may have 1 to 5 (preferably 1 to 3) substituents selected from _-6 alkylaminosulfonyl and the like 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from an atom, oxygen atom and sulfur atom (which may be condensed with a benzene ring) (for example, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl) , Thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxadi Zoriru, thiadiazolyl, furazanyl, indolyl, isoindolyl, benzofuranyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, cinnolinyl, acridinyl, etc.) (more preferably, halogen, respectively, nitro, hydroxy, C _1-6 alkyl which may be halogenated, (I) a C _6-10 aryl group (such as phenyl) or (ii) optionally having 1 to 3 substituents selected from optionally halogenated C _1-6 alkoxy and aminosulfonyl A 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom (a benzene ring may be condensed) (thienyl, indolyl, etc.); ), Or (2) Ar ₂ and L ₂ are bonded to each other to form a formula

[The symbols in the formula are as defined above. ] The compound etc. which are the cases where the ring represented by these are formed are mentioned.

〔式中、Ａｒ_４はアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、Ｃ₁₋₆アルキル−カルボニルアミノおよびＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個の置換基を有し、さらに１ないし４個の置換基を有していてもよいベンゼン環基を示し、その他の記号は前記と同意義を示す。〕で表される化合物（以下、化合物（Ｉｃ）と略記することもある）又はその塩は新規化合物である。
Ａｒ_４で示される「さらに１ないし４個の置換基を有していてもよいベンゼン環基」の「置換基」としては、Ａｒで示される「縮合していてもよい５または６員芳香環基を示し、該芳香環基は置換基を有していてもよく」の「置換基」として挙げた置換基と同様のもの（但し、アミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、Ｃ₁₋₆アルキル−カルボニルアミノおよびＣ₁₋₆アルキルスルホニルアミノを除く）が挙げられる。
化合物（Ｉｃ）として、好ましくは、Ａｒ_４がアミノスルホニル、モノ−又はジ−Ｃ₁₋₆アルキルアミノスルホニル、Ｃ₁₋₆アルキル−カルボニルアミノおよびＣ₁₋₆アルキルスルホニルアミノから選ばれる１または２個（より好ましくは１個）の置換基を有し、さらに１または２個（より好ましくは１個）のＣ_１−４アルコキシを有していてもよいベンゼン環基；
Ｌ_１が−(CH₂)₄−、−(CH₂)₅−、−CHF(CH₂)₃−、−CHF(CH₂)₄−、−CF₂(CH₂)₃−、−CF₂(CH₂)₄−、−(CH₂)₃CH(CH₃)−、−(CH₂)₄CH(CH₃)−等の１または２個のハロゲン原子を有していてもよいＣ₄₋₅アルキレン基（好ましくは無置換Ｃ₄₋₅アルキレン基）；
Ｒが (i)水素原子、(ii)ハロゲン原子（好ましくはフルオロ等）及びヒドロキシから選ばれる置換基を１ないし３個有していてもよいＣ_１-４アルキル基、又は(iii)Ｃ_7-16アラルキル（ベンジル等）等（より好ましくは水素原子またはＣ_１-４アルキル基）；
Ｌ₂がハロゲン原子、ヒドロキシ、オキソ、フェニル等から選ばれる１ないし４個の置換基を有していてもよいＣ_2−４アルキレン基（例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₂)₄−、−CHFCH₂−、−CHF(CH₂)₂−、−CHF(CH₂)₃−、−CF₂CH₂−、−CF₂(CH₂)₂−、−CF₂(CH₂)₃−、−(CH₃)CHCH₂−、−(CH₃)CH(CH₂)₂−、−(CH(CH₃))₂−、−CH₂CH(OH)−、−CH₂CO−、−(Ph)CHCH₂−等）（より好ましくはヒドロキシまたはオキソを有していてもよいＣ_2−３アルキレン基）；
Ｘが結合手、酸素原子又はＮＨ（より好ましくは結合手）；
Ａｒ₂が（1）それぞれ、ハロゲン（フルオロ、クロロ等）、Ｃ_1-6アルキル（メチル、エチル等）、ハロゲノＣ_1-6アルキル（トリフルオロメチル等）、ヒドロキシ、Ｃ_1-6アルコキシ（メトキシ、エトキシ等）、ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ、トリフルオロエトキシ等）、ニトロ、アミノ、シアノ、カルバモイル、Ｃ_1-6アルキルで置換されていてもよいカルバモイル又はホルミルで置換されていてもよいアミノ（ＮＨＣＨＯ、ＮＨＣＯＮＨ₂、ＮＨＣＯＮＨＭｅ等）、Ｃ_1-3アルキレンジオキシ（メチレンジオキシ等）、Ｃ_1-6アルキルで置換されていてもよいアミノカルボニルオキシ基（アミノカルボニルオキシ、メチルアミノカルボニルオキシ、エチルアミノカルボニルオキシ、ジメチルアミノカルボニルオキシ、ジエチルアミノカルボニルオキシ等）、５ないし７員環状アミノ−カルボニルオキシ（ (1-ピロリジニル) カルボニルオキシ、ピペリジノカルボニルオキシ等）、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル及びジ−Ｃ_1-6アルキルアミノスルホニル等から選ばれる１ないし５個（好ましくは１ないし３個）の置換基を有していてもよい、（ｉ）Ｃ_6-10アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（例えば、チエニル、フリル、ピロリル、イミダゾリル、ピラゾリル、チアゾリル、イソチアゾリル、オキサゾリル、イソオキサゾリル、ピリジル、ピラジニル、ピリミジニル、ピリダジニル、オキサジアゾリル、チアジアゾリル、フラザニル、インドリル、イソインドリル、ベンゾフラニル、キノリル、イソキノリル、ナフチリジニル、キナゾリニル、シンノリニル、アクリジニル等）、（2）Ａｒ₂とＲとが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合、または（3）Ａｒ₂とＬ₂とが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合（Ａｒ_２はより好ましくは、それぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、（ｉ）Ｃ₆₋₁₀アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子を１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（チエニル、インドリル等）等である。）
である化合物等が挙げられる。 In addition, among the compounds (I), the formula

[Wherein Ar ₄ represents one or two substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. And a benzene ring group which may further have 1 to 4 substituents, and other symbols are as defined above. ] (Hereinafter also abbreviated as compound (Ic)) or a salt thereof is a novel compound.
As "substituent" of the "optionally further one to four may have a substituent group benzene ring group" represented by Ar _4, "condensed may be 5 or 6-membered aromatic ring represented by Ar The aromatic ring group may have a substituent "and the same as the substituents listed as the" substituent "(however, aminosulfonyl, mono- or di-C _1-6 alkylamino Sulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino).
As compound (Ic), preferably Ar ₄ is selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino Benzene ring group which has 1 (more preferably 1) substituent and may further have 1 or 2 (more preferably 1) C _1-4 alkoxy;
L ₁ is _{- (CH 2) 4 -,} - (CH 2) 5 -, - CHF (CH 2) 3 -, - CHF (CH 2) 4 -, - CF 2 (CH 2) 3 -, - CF 2 C ₄ which may have one or two halogen atoms such as (CH ₂ ) ₄ -,-(CH ₂ ) ₃ CH (CH ₃ )-,-(CH ₂ ) ₄ CH (CH ₃ )- _{A -5} alkylene group (preferably an unsubstituted C _4-5 alkylene group);
R is (i) a hydrogen atom, (ii) a halogen atom (preferably fluoro, etc.) 1 substituent to 3 substituents optionally having C _1-4 alkyl group selected from and hydroxy, or (iii) C _{7 -16} aralkyl (such as benzyl) and the like (more preferably a hydrogen atom or a C _1-4 alkyl group);
L ₂ is a C _2-4 alkylene group (for example, — (CH ₂ ) ₂ —, — (CH ₂ ) _optionally having 1 to 4 substituents selected from a halogen atom, hydroxy, oxo, phenyl and the like. ) ₃ −, − (CH ₂ ) ₄ −, −CHFCH ₂ −, −CHF (CH ₂ ) ₂ −, −CHF (CH ₂ ) ₃ −, −CF ₂ CH ₂ −, −CF ₂ (CH ₂ ) ₂ -, --CF ₂ (CH ₂ ) ₃ -,-(CH ₃ ) CHCH ₂ -,-(CH ₃ ) CH (CH ₂ ) ₂ -,-(CH (CH ₃ )) _2- , --CH ₂ CH ( _{OH) -, - CH 2 CO} -, - (Ph) CHCH 2 - , etc.) (more preferably in C _2-3 alkylene group optionally having a hydroxy or oxo);
X is a bond, an oxygen atom or NH (more preferably a bond);
Ar ₂ is (1) halogen (fluoro, chloro, etc.), C _1-6 alkyl (methyl, ethyl, etc.), halogeno C _1-6 alkyl (trifluoromethyl, etc.), hydroxy, C _1-6 alkoxy (methoxy), respectively. , Ethoxy, etc.), halogeno C _1-6 alkoxy (trifluoromethoxy, trifluoroethoxy, etc.), nitro, amino, cyano, carbamoyl, substituted with carbamoyl or formyl optionally substituted with C _1-6 alkyl Amino (NHCHO, NHCONH ₂ , NHCONHMe, etc.), C _1-3 alkylenedioxy (methylenedioxy, etc.), aminocarbonyloxy group (aminocarbonyloxy, methylamino) optionally substituted by C _1-6 alkyl Carbonyloxy, ethylaminocarbonyloxy, dimethylaminocarbonyloxy, diethyl ), 5- to 7-membered cyclic amino-carbonyloxy ((1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy etc.), aminosulfonyl, mono-C _1-6 alkylaminosulfonyl and di-C ₁ (I) a C _6-10 aryl group (such as phenyl) or (ii) nitrogen which may have 1 to 5 (preferably 1 to 3) substituents selected from _-6 alkylaminosulfonyl and the like 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from an atom, oxygen atom and sulfur atom (which may be condensed with a benzene ring) (for example, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl) , Thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxadi Zoriru, thiadiazolyl, furazanyl, indolyl, isoindolyl, benzofuranyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, cinnolinyl, acridinyl, etc.), (2) Ar ₂ and the R are bonded to each other, wherein

[The symbols in the formula are as defined above. Or (3) Ar ₂ and L ₂ are bonded to each other to form a ring represented by the formula

[The symbols in the formula are as defined above. (Ar ₂ is more preferably halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, and optionally halogenated C _1-6 alkoxy, respectively. And (i) a C _6-10 aryl group (such as phenyl) or (ii) a hetero atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, which may have 1 to 3 substituents selected from aminosulfonyl And a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 atoms (a benzene ring may be condensed) (thienyl, indolyl, etc.).
The compound etc. which are are mentioned.

〔式中、ｎは１または２の整数を示し、Ｌ_４は置換基を有していてもよいＣ_３−５アルキレン基を示し、その他の記号は前記と同意義を示す。〕で表される化合物（以下、化合物（Ｉｄ）と略記することもある）又はその塩は新規化合物である。
Ｌ_４で示される「置換基を有していてもよいＣ_３−５アルキレン基」としては、Ｌで示される「置換基を有していてもよい主鎖の原子数１ないし１０のスペーサー」において例示した、「Ｃ_1-10アルキレン基」のうち、炭素鎖数３ないし５のものが挙げられる。
Ｌ_４で示される「置換基を有していてもよいＣ_３−５アルキレン基」における「置換基」としては、Ｌで示される「置換基を有していてもよい主鎖の原子数１ないし１０のスペーサー」における「置換基」と同様のものが挙げられる。好ましくは、例えばハロゲン原子(例、フッ素、塩素、臭素、ヨウ素など)、ニトロ、シアノ、ハロゲン化されていてもよいC_1-6アルコキシ、ヒドロキシなどから選ばれる１ないし４個の置換基が挙げられる。
化合物（Ｉｄ）として、好ましくは、Ｒ^１及びＲ¹'が水素原子またはハロゲン化されていてもよいＣ_1-6アルキル基（メチル、エチル、トリフルオロメチル等）；
Ｌ₄が−(CH₂)₃−、−(CH₂)₄−、−(CH₂)₅−、−CHF(CH₂)₂−、−CHF(CH₂)₃−、−CF₂(CH₂)₂−、−CF₂(CH₂)₃−、−(CH₂)₂CH(CH₃)−、−(CH₂)₃CH(CH₃)−等の１または２個のハロゲン原子を有していてもよいＣ_３−５アルキレン基（より好ましくはＣ_３−４アルキレン基）；
Ｒが (i)水素原子、(ii)ハロゲン原子（好ましくはフルオロ等）及びヒドロキシから選ばれる置換基を１ないし３個有していてもよいＣ_１-４アルキル基、又は(iii)Ｃ_7-16アラルキル（ベンジル等）等（より好ましくは水素原子またはＣ_１-４アルキル基）；
Ｌ₂がハロゲン原子、ヒドロキシ、オキソ、フェニル等から選ばれる１ないし４個の置換基を有していてもよいＣ_2−４アルキレン基（例えば、−(CH₂)₂−、−(CH₂)₃−、−(CH₂)₄−、−CHFCH₂−、−CHF(CH₂)₂−、−CHF(CH₂)₃−、−CF₂CH₂−、−CF₂(CH₂)₂−、−CF₂(CH₂)₃−、−(CH₃)CHCH₂−、−(CH₃)CH(CH₂)₂−、−(CH(CH₃))₂−、−CH₂CH(OH)−、−CH₂CO−、−(Ph)CHCH₂−等）（より好ましくはヒドロキシまたはオキソを有していてもよいＣ_2−３アルキレン基）；
Ｘが結合手、酸素原子又はＮＨ（より好ましくは結合手）；
Ａｒ₂が（1）それぞれ、ハロゲン（フルオロ、クロロ等）、Ｃ_1-6アルキル（メチル、エチル等）、ハロゲノＣ_1-6アルキル（トリフルオロメチル等）、ヒドロキシ、Ｃ_1-6アルコキシ（メトキシ、エトキシ等）、ハロゲノＣ_1-6アルコキシ（トリフルオロメトキシ、トリフルオロエトキシ等）、ニトロ、アミノ、シアノ、カルバモイル、Ｃ_1-6アルキルで置換されていてもよいカルバモイル又はホルミルで置換されていてもよいアミノ（ＮＨＣＨＯ、ＮＨＣＯＮＨ₂、ＮＨＣＯＮＨＭｅ等）、Ｃ_1-3アルキレンジオキシ（メチレンジオキシ等）、Ｃ_1-6アルキルで置換されていてもよいアミノカルボニルオキシ基（アミノカルボニルオキシ、メチルアミノカルボニルオキシ、エチルアミノカルボニルオキシ、ジメチルアミノカルボニルオキシ、ジエチルアミノカルボニルオキシ等）、５ないし７員環状アミノ−カルボニルオキシ（ (1-ピロリジニル) カルボニルオキシ、ピペリジノカルボニルオキシ等）、アミノスルホニル、モノ−Ｃ_1-6アルキルアミノスルホニル及びジ−Ｃ_1-6アルキルアミノスルホニル等から選ばれる１ないし５個（好ましくは１ないし３個）の置換基を有していてもよい、（ｉ）Ｃ_6-10アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（例えば、チエニル、フリル、ピロリル、イミダゾリル、ピラゾリル、チアゾリル、イソチアゾリル、オキサゾリル、イソオキサゾリル、ピリジル、ピラジニル、ピリミジニル、ピリダジニル、オキサジアゾリル、チアジアゾリル、フラザニル、インドリル、イソインドリル、ベンゾフラニル、キノリル、イソキノリル、ナフチリジニル、キナゾリニル、シンノリニル、アクリジニル等）、（2）Ａｒ₂とＲとが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合、または（3）Ａｒ₂とＬ₂とが互いに結合して、式

〔式中の記号は前記と同意義を示す。〕で表される環を形成する場合（Ａｒ_２はより好ましくは、それぞれハロゲン、ニトロ、ヒドロキシ、ハロゲン化されていてもよいＣ₁₋₆アルキル、ハロゲン化されていてもよいＣ₁₋₆アルコキシおよびアミノスルホニルから選ばれる１ないし３個の置換基を有していてもよい、（ｉ）Ｃ₆₋₁₀アリール基（フェニル等）または（ii）窒素原子、酸素原子及び硫黄原子から選ばれるヘテロ原子を１ないし４個を含む５または６員芳香族複素環基（ベンゼン環が縮合していてもよい）（チエニル、インドリル等）等である。）
である化合物等が挙げられる。 In addition, among the compounds (I), the formula

[Wherein, n represents an integer of 1 or 2, L ₄ represents a C _3-5 alkylene group which may have a substituent, and other symbols are as defined above]. ] (Hereinafter also abbreviated as compound (Id)) or a salt thereof is a novel compound.
The “C _3-5 alkylene group _optionally having substituent (s)” represented by L ₄ is the “spacer having 1 to 10 atoms in the main chain optionally having substituent (s)” represented by L. Among the “C _1-10 alkylene group” exemplified in the above, those having 3 to 5 carbon chains can be mentioned.
L as "substituent" in the "optionally substituted C _3-5 alkylene group" represented by _4, the number atoms "in the main may be substituted chains represented by L 1 And the same as the “substituent” in “10 to 10 spacers”. Preferable examples include 1 to 4 substituents selected from, for example, a halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), nitro, cyano, optionally halogenated C _1-6 alkoxy, hydroxy and the like. It is done.
As compound (Id), R ¹ and R ¹ ′ are preferably a hydrogen atom or a C _1-6 alkyl group which may be halogenated (methyl, ethyl, trifluoromethyl, etc.);
L ₄ is-(CH ₂ ) ₃ -,-(CH ₂ ) ₄ -,-(CH ₂ ) _5- , -CHF (CH ₂ ) _2- , -CHF (CH ₂ ) _3- , -CF ₂ (CH _{2) 2 -, - CF 2} (CH 2) 3 -, - (CH 2) 2 CH (CH 3) -, - one or two halogen atoms, such as _{- (CH 2) 3 CH (} CH 3) An _optionally substituted C _3-5 alkylene group (more preferably a C _3-4 alkylene group);
R is (i) a hydrogen atom, (ii) a halogen atom (preferably fluoro, etc.) 1 substituent to 3 substituents optionally having C _1-4 alkyl group selected from and hydroxy, or (iii) C _{7 -16} aralkyl (such as benzyl) and the like (more preferably a hydrogen atom or a C _1-4 alkyl group);
L ₂ is a C _2-4 alkylene group (for example, — (CH ₂ ) ₂ —, — (CH ₂ ) _optionally having 1 to 4 substituents selected from a halogen atom, hydroxy, oxo, phenyl and the like. ) ₃ −, − (CH ₂ ) ₄ −, −CHFCH ₂ −, −CHF (CH ₂ ) ₂ −, −CHF (CH ₂ ) ₃ −, −CF ₂ CH ₂ −, −CF ₂ (CH ₂ ) ₂ -, --CF ₂ (CH ₂ ) ₃ -,-(CH ₃ ) CHCH ₂ -,-(CH ₃ ) CH (CH ₂ ) ₂ -,-(CH (CH ₃ )) _2- , --CH ₂ CH ( _{OH) -, - CH 2 CO} -, - (Ph) CHCH 2 - , etc.) (more preferably in C _2-3 alkylene group optionally having a hydroxy or oxo);
X is a bond, an oxygen atom or NH (more preferably a bond);
Ar ₂ is (1) halogen (fluoro, chloro, etc.), C _1-6 alkyl (methyl, ethyl, etc.), halogeno C _1-6 alkyl (trifluoromethyl, etc.), hydroxy, C _1-6 alkoxy (methoxy), respectively. , Ethoxy, etc.), halogeno C _1-6 alkoxy (trifluoromethoxy, trifluoroethoxy, etc.), nitro, amino, cyano, carbamoyl, substituted with carbamoyl or formyl optionally substituted with C _1-6 alkyl Amino (NHCHO, NHCONH ₂ , NHCONHMe, etc.), C _1-3 alkylenedioxy (methylenedioxy, etc.), aminocarbonyloxy group (aminocarbonyloxy, methylamino) optionally substituted by C _1-6 alkyl Carbonyloxy, ethylaminocarbonyloxy, dimethylaminocarbonyloxy, diethyl ), 5- to 7-membered cyclic amino-carbonyloxy ((1-pyrrolidinyl) carbonyloxy, piperidinocarbonyloxy etc.), aminosulfonyl, mono-C _1-6 alkylaminosulfonyl and di-C ₁ (I) a C _6-10 aryl group (such as phenyl) or (ii) nitrogen which may have 1 to 5 (preferably 1 to 3) substituents selected from _-6 alkylaminosulfonyl and the like 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from an atom, oxygen atom and sulfur atom (which may be condensed with a benzene ring) (for example, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl) , Thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxadi Zoriru, thiadiazolyl, furazanyl, indolyl, isoindolyl, benzofuranyl, quinolyl, isoquinolyl, naphthyridinyl, quinazolinyl, cinnolinyl, acridinyl, etc.), (2) Ar ₂ and the R are bonded to each other, wherein

[The symbols in the formula are as defined above. Or (3) Ar ₂ and L ₂ are bonded to each other to form a ring represented by the formula

[The symbols in the formula are as defined above. (Ar ₂ is more preferably halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, and optionally halogenated C _1-6 alkoxy, respectively. And (i) a C _6-10 aryl group (such as phenyl) or (ii) a hetero atom selected from a nitrogen atom, an oxygen atom and a sulfur atom, which may have 1 to 3 substituents selected from aminosulfonyl And a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 atoms (a benzene ring may be condensed) (thienyl, indolyl, etc.).
The compound etc. which are are mentioned.

When compound (I), (Ia), (Ib), (Ic) or (Id) (hereinafter referred to as compound B) is a salt, examples of such a salt include a salt with an inorganic base, Examples include ammonium salts, salts with organic bases, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids, and the like.
Preferable examples of the salt with an inorganic base include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt, magnesium salt and barium salt; aluminum salt and the like.
Preferable examples of the salt with an organic base include salts with trimethylamine, triethylamine, pyridine, picoline, ethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, N, N-dibenzylethylenediamine and the like.
Preferable examples of the salt with inorganic acid include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
Preferable examples of the salt with organic acid include, for example, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, and salts with p-toluenesulfonic acid.
Preferable examples of salts with basic amino acids include salts with arginine, lysine, ornithine and the like, and preferable examples of salts with acidic amino acids include salts with aspartic acid, glutamic acid and the like. Is mentioned.
Of these salts, pharmaceutically acceptable salts are preferred. For example, when the compound B has an acidic functional group, an inorganic salt such as an alkali metal salt (for example, sodium salt, potassium salt) and an alkaline earth metal salt (for example, calcium salt, magnesium salt, barium salt), An ammonium salt may be used. In addition, when compound B has a basic functional group, inorganic salt such as hydrochloride, sulfate, phosphate, hydrobromide; or acetate, maleate, fumarate, succinate, Organic salts such as methanesulfonate, p-toluenesulfonate, citrate, and tartrate may also be used.

Compound B may be either an anhydride or a hydrate. In the case of a hydrate, it may have 0.1 to 5 water molecules.
Further, Compound B may be labeled with an isotope (eg, ³ H, ¹⁴ C, ³⁵ S, etc.).
When Compound B contains optical isomers, stereoisomers, positional isomers, and rotational isomers, these are also included as the compounds of the present invention, and each of them as a single product by a known synthesis method and separation method. Obtainable. For example, when Compound B has an optical isomer, the optical isomer resolved from the compound is also included in Compound B.
The optical isomer can be produced by a method known per se. Specifically, an optical isomer is obtained by using an optically active synthetic compound or optically resolving a final racemic mixture according to a conventional method.
As the optical resolution method, a method known per se, for example, a fractional recrystallization method, a chiral column method, a diastereomer method and the like described in detail below are used.
1) Fractional recrystallization method Racemate and optically active compound (e.g., (+)-mandelic acid, (-)-mandelic acid, (+)-tartaric acid, (-)-tartaric acid, (+)-1-phenethylamine, (-)-1-phenethylamine, cinchonine, (-)-cinchonidine, brucine, etc.) to form a salt, which is separated by fractional recrystallization, and if desired, a free optical isomer is obtained through a neutralization step. Method.
2) Chiral column method A method in which a racemate or a salt thereof is separated by applying to a column for optical isomer separation (chiral column). For example, in the case of liquid chromatography, a mixture of optical isomers is added to a chiral column such as ENANTIO-OVM (manufactured by Tosoh Corporation) or CHIRAL series manufactured by Daicel Corporation, water, various buffers (for example, phosphate buffer), Optical isomers are separated by developing an organic solvent (for example, ethanol, methanol, isopropanol, acetonitrile, trifluoroacetic acid, diethylamine, etc.) as a single or mixed solution. In addition, for example, in the case of gas chromatography, separation is performed using a chiral column such as CP-Chirasil-DeXCB (manufactured by GL Sciences).
3) Diastereomer method A mixture of racemates is converted into a mixture of diastereomers by chemical reaction with an optically active reagent, and this is converted into a single substance through ordinary separation means (for example, fractional recrystallization, chromatography method, etc.). Then, the optical isomer is obtained by separating the optically active reagent site by chemical treatment such as hydrolysis reaction. For example, when Compound B has hydroxy or 1,2 secondary amino in the molecule, the compound and an optically active organic acid (for example, MTPA [α-methoxy-α- (trifluoromethyl) phenylacetic acid], (−) -Mentoxyacetic acid and the like) can be subjected to a condensation reaction to obtain ester or amide diastereomers, respectively. On the other hand, when Compound B has a carboxylic acid group, an amide or ester diastereomer is obtained by subjecting the compound and an optically active amine or alcohol reagent to a condensation reaction. The separated diastereomer is converted into the optical isomer of the original compound by subjecting it to an acid hydrolysis or basic hydrolysis reaction.

A prodrug of Compound B is a compound that is converted to Compound B by a reaction with an enzyme, gastric acid or the like under physiological conditions in vivo, that is, a compound that is enzymatically oxidized, reduced, hydrolyzed, etc., and converted to Compound B, gastric acid The compound which raise | generates hydrolysis etc. by etc. and changes to the compound B is said. As a prodrug of compound B, a compound in which the amino group of compound B is acylated, alkylated or phosphorylated [eg, the amino group of compound B is eicosanoylated, alanylated, pentylaminocarbonylated, (5-methyl- 2-oxo-1,3-dioxolen-4-yl) methoxycarbonylation, tetrahydrofuranylation, pyrrolidylmethylation, pivaloyloxymethylation, tert-butylated compounds, etc.]; the hydroxyl group of compound B is acyl , Alkylated, phosphorylated, borated compounds (eg, compounds in which the hydroxyl group of compound B is acetylated, palmitoylated, propanoylated, pivaloylated, succinylated, fumarylated, alanylated, dimethylaminomethylcarbonylated) Etc.); Compound B in which the carboxyl group is esterified or amidated Examples, Compound B carboxyl group is ethyl esterification, phenyl esterification, carboxymethyl esterification, dimethylaminomethyl esterification, pivaloyloxymethyl esterification, ethoxycarbonyloxyethyl esterification, phthalidyl esterification, (5- Methyl-2-oxo-1,3-dioxolen-4-yl) methyl esterification, cyclohexyloxycarbonylethyl esterification, methylamidated compounds, and the like]. These compounds can be produced from compound B by a method known per se.
Further, the prodrug of Compound B may be one that changes to Compound B under physiological conditions, as described in Hirokawa Shoten, 1990, “Pharmaceutical Development”, Volume 7, Molecular Design, pages 163 to 198. Good.

Next, production methods of compounds (Ia), (Ib), (Ic) and (Id) will be described. Compound (I) is produced according to the production methods of (Ia), (Ib), (Ic) and (Id) shown below.
Compounds (Ia), (Ic) and (Id) are produced, for example, by the following [Production Method A] and [Production Method B], and Compound (Ib) is produced, for example, by the following [Production Method C]. . In [Production Method A]-[Production Method C], alkylation reaction, hydrolysis reaction, amination reaction, esterification reaction, amidation reaction, esterification reaction, etherification reaction, oxidation reaction, reduction reaction, reductive amino These reactions are carried out according to a method known per se. Such methods include, for example, ORGANIC FUNCTIONAL GROUP PREPARATIONS, 2nd edition, ACADEMIC PRESS, INC., 1989; Comprehensive Organic Transformations (Comprehensive Organic Transformations) Examples include the methods described in VCH Publishers Inc., 1989.
In the production methods described below, compounds (II), (II ′), (II ″), (III), (IV), (V), (VI), (VI ′), (VI ″) , (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), ( XIX), (XX) and (XXI) may each form a salt. As the “salt”, for example, the “salt” in the above “in the case where the compound B is a salt” can be applied.

[式中、Ｚ₁は脱離基を、その他の各記号は前記と同意義を示す。]
Ｚ₁で示される「脱離基」としては、例えばハロゲン原子（例えばクロル、ブロム、ヨード）、Ｃ_1-6アルキルスルホニルオキシ（例えば、メタンスルホニルオキシ、エタンスルホニルオキシ、トリフルオロメタンスルホニルオキシ）、Ｃ_6-10アリールスルホニルオキシ（例えばベンゼンスルホニルオキシ、ｐ−トルエンスルホニルオキシ）などが用いられる。特にハロゲン原子（例えば、クロル、ブロムなど）、メタンスルホニルオキシ等が好ましい。
本カップリング反応は、無溶媒あるいは適当な溶媒、例えば炭化水素系溶媒、アルコール系溶媒、エーテル系溶媒、ハロゲン化炭化水素系溶媒、芳香族系溶媒、ニトリル系溶媒、アミド系溶媒、ケトン系溶媒、スルホキシド系溶媒、カルボン酸系溶媒、水等に溶解または縣濁して行うことができる。これらは、二種以上を適宜の割合で混合して用いてもよい。好ましくは、例えば無溶媒、あるいはエタノール等のアルコール系溶媒、トルエン等の芳香族系溶媒、ジメチルホルムアミド等のアミド系溶媒等が用いられる。
また、本カップリング反応は適当な塩基を添加して行ってもよい。また、該塩基を溶媒として用いることもできる。
「塩基」としては例えば、
１）例えば、アルカリ金属またはアルカリ土類金属の水素化物（例、水素化リチウム、水素化ナトリウム、水素化カリウム、水素化カルシウムなど）、アルカリ金属またはアルカリ土類金属のアミド類（例、リチウムアミド、ナトリウムアミド、リチウムジイソプロピルアミド、リチウムジシクロヘキシルアミド、リチウムヘキサメチルジシラジド、ナトリウムヘキサメチルジシラジド、カリウムヘキサメチルジシラジドなど）、アルカリ金属またはアルカリ土類金属の低級アルコキシド（例、ナトリウムメトキシド、ナトリウムエトキシド、カリウム ｔｅｒｔ−ブトキシドなど）などの強塩基；
２）例えば、アルカリ金属またはアルカリ土類金属の水酸化物（例、水酸化ナトリウム、水酸化カリウム、水酸化リチウム、水酸化バリウムなど）、アルカリ金属またはアルカリ土類金属の炭酸塩（例、炭酸ナトリウム、炭酸カリウム、炭酸セシウムなど）、アルカリ金属またはアルカリ土類金属の炭酸水素塩（例、炭酸水素ナトリウム、炭酸水素カリウムなど）などの無機塩基；および
３）例えば、トリエチルアミン、ジイソプロピルエチルアミン、Ｎ−メチルモルホリンなどのアミン類；例えばＤＢＵ（１，８−ジアザビシクロ〔５．４．０〕ウンデス−７−エン）、ＤＢＮ（１，５−ジアザビシクロ〔４．３．０〕ノン−５−エン）などのアミジン類；例えばピリジン、ジメチルアミノピリジン、イミダゾール、２，６−ルチジンなどの塩基性複素環化合物などの有機塩基などが挙げられる。
「塩基」としては、例えば炭酸カリウム等のアルカリ金属塩、トリエチルアミン、ジイソプロピルエチルアミン等のアミン類等が好ましい。
本カップリング反応の際、化合物（III）の水素原子をあらかじめ金属原子、例えばリチウム、ナトリウム等のアルカリ金属等で置換しておいてもよい。
本カップリング反応は、-100℃ないし300℃で行うことができるが、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし１日である。
本カップリング反応は、化合物（II）、（II'）または（II”）と化合物（III）を任意の比率で行うことができ、さらにどちらかを溶媒として用いることもできる。
化合物（III）は、それ自体公知あるいはそれに準じた方法により製造することができる。例えば、コンプリヘンシブ オーガニック トランスフォーメーション(Comprehensive Organic Transformation) VCH Publishers Inc.，1989年刊等に記載の方法、具体的には、ジャーナル オブ ジ オーガニック ケミストリー（J. Org. Chem.） 24, 1106 (1959)、ブリティン オブ ザ ケミカル ソサイエティー オブ ジャパン（Bull. Chem. Soc. Jpn.） 63, 1252 (1990)、シンセティック コミュニケーションズ(Synth. Commun.) 14, 1099 (1984)、テトラヘドロン(Tetrahedron)49, 1807 (1993)、ジャーナル オブ ヘテロサイクリック ケミストリー(J. Heterocyclic Chem.) 28, 1587(1991)、ジャーナル オブ ジ オーガニック ケミストリー（J. Org. Chem.） 60, 7086 (1995) 等に記載の方法あるいはそれに準じた方法によって製造することができる。 [Production Method A] A method for producing compound (Ia), (Ic) or (Id) by a coupling reaction of compound (II), (II ′) or (II ″) and compound (III).

[Wherein Z ₁ represents a leaving group, and other symbols are as defined above. ]
Examples of the “leaving group” represented by Z ₁ include a halogen atom (eg, chloro, bromo, iodo), C _1-6 alkylsulfonyloxy (eg, methanesulfonyloxy, ethanesulfonyloxy, trifluoromethanesulfonyloxy), C _6-10 arylsulfonyloxy (for example, benzenesulfonyloxy, p-toluenesulfonyloxy) and the like are used. In particular, a halogen atom (for example, chloro, bromo and the like), methanesulfonyloxy and the like are preferable.
This coupling reaction may be carried out in the absence of a solvent or in a suitable solvent such as a hydrocarbon solvent, alcohol solvent, ether solvent, halogenated hydrocarbon solvent, aromatic solvent, nitrile solvent, amide solvent, ketone solvent. , A sulfoxide solvent, a carboxylic acid solvent, water or the like. These may be used as a mixture of two or more at an appropriate ratio. Preferably, for example, no solvent, or an alcohol solvent such as ethanol, an aromatic solvent such as toluene, an amide solvent such as dimethylformamide, or the like is used.
In addition, this coupling reaction may be performed by adding an appropriate base. The base can also be used as a solvent.
As the “base”, for example,
1) For example, alkali metal or alkaline earth metal hydrides (eg, lithium hydride, sodium hydride, potassium hydride, calcium hydride, etc.), alkali metal or alkaline earth metal amides (eg, lithium amide) Sodium amide, lithium diisopropylamide, lithium dicyclohexylamide, lithium hexamethyldisilazide, sodium hexamethyldisilazide, potassium hexamethyldisilazide), alkali metal or alkaline earth metal lower alkoxides (eg, sodium methoxy) Strong base such as sodium ethoxide, potassium tert-butoxide, etc.);
2) For example, alkali metal or alkaline earth metal hydroxides (eg, sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, etc.), alkali metal or alkaline earth metal carbonates (eg, carbonic acid) Sodium, potassium carbonate, cesium carbonate, etc.), alkali metal or alkaline earth metal hydrogen carbonates (eg, sodium bicarbonate, potassium bicarbonate, etc.); and 3) eg, triethylamine, diisopropylethylamine, N- Amines such as methylmorpholine; for example, DBU (1,8-diazabicyclo [5.4.0] undes-7-ene), DBN (1,5-diazabicyclo [4.3.0] non-5-ene), etc. Amidines such as pyridine, dimethylaminopyridine, imidazole, 2,6-lutidine, etc. And organic bases such as basic heterocyclic compounds.
As the “base”, for example, alkali metal salts such as potassium carbonate and amines such as triethylamine and diisopropylethylamine are preferable.
In this coupling reaction, the hydrogen atom of compound (III) may be substituted in advance with a metal atom, for example, an alkali metal such as lithium or sodium.
The coupling reaction can be performed at -100 ° C to 300 ° C, preferably 0 ° C to 150 ° C. The reaction time is, for example, 1 minute to 1 day.
In this coupling reaction, compound (II), (II ′) or (II ″) and compound (III) can be carried out in any ratio, and either of them can be used as a solvent.
Compound (III) can be produced by a method known per se or a method analogous thereto. For example, the method described in Comprehensive Organic Transformation VCH Publishers Inc., published in 1989, specifically, Journal of the Organic Chemistry (J. Org. Chem.) 24, 1106 (1959) , Bulletin of the Chemical Society of Japan (Bull. Chem. Soc. Jpn.) 63, 1252 (1990), Synth. Commun. 14, 1099 (1984), Tetrahedron 49, 1807 (1993) ), Journal of Heterocyclic Chem. (J. Heterocyclic Chem.) 28, 1587 (1991), Journal of the Organic Chemistry (J. Org. Chem.) 60, 7086 (1995), etc. It can be manufactured by a method.

[式中、Ｚ₂は脱離基を、その他の各記号は前記と同意義を示す。]
Ｚ₂で示される「脱離基」としては、前記Ｚ₁と同様のものを適用できる。好ましくは、ハロゲン原子（例えば、クロル、ブロムなど）あるいは水酸基である。
本反応は、好ましくは酸触媒を添加して反応を行うことができるが、酸触媒を添加せずに反応を行うこともできる。反応に用いられる酸触媒としては、例えば硫酸、無水リン酸、ポリリン酸等の鉱酸、塩化アルミニウム、四塩化スズ、四塩化チタン、三フッ化ホウ素、トリエチルアルミニウム、ジエチルアルミニウムクロリド、塩化亜鉛等のルイス酸等を用いることができる。好ましくは、ポリリン酸、塩化アルミニウム、ジエチルアルミニウムクロリド、塩化亜鉛等が挙げられる。酸触媒は、任意の当量を用いることができるが、通常、化合物（ＩＶ）あるいは化合物（Ｖ）に対して0.1当量ないし10当量である。また、場合によっては酸触媒を溶媒として用いることもできる。
本反応は、無溶媒あるいは適当な溶媒、例えば炭化水素系溶媒、エーテル系溶媒、ハロゲン化炭化水素系溶媒、ニトロ化炭化水素系溶媒、芳香族系溶媒、ニトリル系溶媒、アミド系溶媒、ケトン系溶媒、スルホキシド系溶媒、カルボン酸系溶媒等に溶解または縣濁して行うことができる。これらは、二種以上を適宜の割合で混合して用いてもよい。好ましくは、例えば無溶媒、あるいはジクロロメタン、１，２−ジクロロエタン等のハロゲン化炭化水素系溶媒、ニトロメタン等のニトロ化炭化水素系溶媒、ニトロベンゼン等の芳香族系溶媒、二硫化炭素等が用いられる。
本反応は、-100℃ないし300℃で行うことができるが、通常、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし３日である。
本反応は、化合物（ＩＶ）と化合物（Ｖ）を任意の比率で行うことができ、さらにどちらかを溶媒として用いることもできる。
化合物（ＩＶ）は、それ自体公知あるいはそれに準じた方法により製造することができる。例えばシンセシス(Synthesis)10, 862 (1984)、ジャーナル オブ ザ ケミカル ソサイエティー(J. Chem. Soc.) 1518 (1964)、シンセシス(Synthesis) 851 (1984)、特開平9−124605等に記載の方法あるいはそれに準じた方法によって製造することができる。
化合物（Ｖ）は、それ自体公知あるいはそれに準じた方法により製造することができる。例えばオーガニック シンセシス(Org. Syn.) Coll. Vol.1, 12 (1941)、ヘルベチカ ヒミカ アクタ(Helv. Chem. Acta) 42, 1653 (1959) 等に記載の方法あるいはそれに準じた方法によって製造することができる。
化合物（II）または（II'）は、上述したフリーデル−クラフツ反応以外の方法でも製造できる。「フリーデル−クラフツ反応以外の方法」としては、例えばテトラへドロン レターズ(Tetrahedron Lett.)27, 929 (1986)、ジャーナル オブ ジ アメリカン ケミカル ソサイエティー(J. Am. Chem. Soc.) 70, 426(1948)、シンレット(Synlett) 3, 225 (1996) 等に記載されたアリールマグネシウム試薬を用いる方法、テトラヘドロン(Tetrahedron)46, 6061(1990) 等に記載の有機亜鉛試薬を用いる方法等、有機金属試薬を用いる方法等が挙げられる。また、例えば特開平3-95143等に記載の活性メチレン誘導体からの合成法等を用いて製造することもできる。 Compound (II) or (II ′) can be produced, for example, by a method such as the Friedel-Crafts reaction as shown below.

[Wherein Z ₂ represents a leaving group, and other symbols are as defined above. ]
As the “leaving group” represented by Z ₂ , those similar to Z ₁ can be applied. Preferably, it is a halogen atom (for example, chloro, bromo, etc.) or a hydroxyl group.
This reaction can be preferably carried out by adding an acid catalyst, but can also be carried out without adding an acid catalyst. Examples of the acid catalyst used in the reaction include mineral acids such as sulfuric acid, phosphoric anhydride and polyphosphoric acid, aluminum chloride, tin tetrachloride, titanium tetrachloride, boron trifluoride, triethylaluminum, diethylaluminum chloride, zinc chloride and the like. Lewis acid or the like can be used. Preferably, polyphosphoric acid, aluminum chloride, diethylaluminum chloride, zinc chloride, etc. are mentioned. The acid catalyst can be used in any equivalent amount, and is usually 0.1 equivalent to 10 equivalents relative to compound (IV) or compound (V). In some cases, an acid catalyst can be used as a solvent.
This reaction can be carried out in the absence of a solvent or an appropriate solvent such as a hydrocarbon solvent, an ether solvent, a halogenated hydrocarbon solvent, a nitrated hydrocarbon solvent, an aromatic solvent, a nitrile solvent, an amide solvent, a ketone solvent. It can be carried out by dissolving or suspending in a solvent, a sulfoxide solvent, a carboxylic acid solvent or the like. These may be used as a mixture of two or more at an appropriate ratio. Preferably, for example, no solvent, halogenated hydrocarbon solvents such as dichloromethane and 1,2-dichloroethane, nitrated hydrocarbon solvents such as nitromethane, aromatic solvents such as nitrobenzene, carbon disulfide and the like are used.
This reaction can be carried out at -100 ° C to 300 ° C, but usually 0 ° C to 150 ° C is preferred. The reaction time is, for example, 1 minute to 3 days.
In this reaction, compound (IV) and compound (V) can be carried out at an arbitrary ratio, and either of them can be used as a solvent.
Compound (IV) can be produced by a method known per se or a method analogous thereto. For example, Synthesis 10, 862 (1984), Journal of the Chemical Society (J. Chem. Soc.) 1518 (1964), Synthesis 851 (1984), JP-A-9-124605, etc. It can be produced by a method according to it.
Compound (V) can be produced by a method known per se or a method analogous thereto. For example, organic synthesis (Org. Syn.) Coll. Vol.1, 12 (1941), Helvetica Himika Acta 42, 1653 (1959), etc. Can do.
Compound (II) or (II ′) can also be produced by methods other than the Friedel-Crafts reaction described above. Examples of "methods other than Friedel-Crafts reaction" include Tetrahedron Lett. 27, 929 (1986), Journal of the American Chemical Society 70, 426 ( 1948), a method using an arylmagnesium reagent described in Synlett 3, 225 (1996), etc., a method using an organozinc reagent described in Tetrahedron 46, 6061 (1990), etc. Examples include a method using a reagent. Further, for example, it can also be produced using a synthesis method from an active methylene derivative described in JP-A-3-95143 and the like.

[式中、置換基Ｖは電子吸引基を、Ｚ_３は脱離基を、その他の各記号は前記と同意義を示す。]
置換基Ｖで示される「電子吸引基」としては、例えばＣ_1-８アルコキシカルボニル基（例えば、メトキシカルボニル、ｔｅｒｔ−ブトキシカルボニル基など）、Ｃ_7-16アラルキルオキシカルボニル基（例えば、ベンジルオキシカルボニル基など）、カルボキシル基、シアノ基等が用いられる。好ましくはＣ_1-４アルコキシカルボニル基（例えば、メトキシカルボニル、ｔｅｒｔ−ブトキシカルボニル基など）である。
Ｚ_３で示される「脱離基」としては、前記Ｚ₁と同様のものを適用できる。好ましくは、ハロゲン原子（例えば、クロル、ブロムなど）、ｐ−トルエンスルホニルオキシ基あるいはメタンスルホニルオキシ基である。
「置換基Ｖの導入」反応は、無溶媒あるいは適当な溶媒中で行うことができる。「溶媒」は前記製造法Ａで述べた「溶媒」と同様なものを用いることができるが、例えば無溶媒、あるいはテトラヒドロフラン等のエーテル系溶媒、トルエン等の芳香族系溶媒、ジメチルホルムアミド等のアミド系溶媒等が好ましい。
本「置換基Ｖの導入」反応における置換基Ｖの前駆体としては、例えば炭酸エステル（炭酸ジメチル等）、ハロ炭酸エステル（クロロ炭酸メチル等）あるいは二酸化炭素等が用いられる。
また、本「置換基Ｖの導入」反応は適当な塩基を添加して行ってもよい。また、該塩基を溶媒として用いることもできる。「塩基」は前記製造法Ａで述べた「塩基」と同様なものを用いることができるが、例えば水素化ナトリウム、ナトリウムアミド、リチウムジイソプロピルアミド等が好ましい。
本「置換基Ｖの導入」反応は、-100℃ないし300℃で行うことができるが、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし１日である。
化合物（ＸＩＩＩ）と化合物（ＸＩＶ）とのカップリング反応は、無溶媒あるいは適当な溶媒中で行うことができる。「溶媒」は前記製造法Ａで述べた「溶媒」と同様なものを用いることができるが、例えば無溶媒、あるいはテトラヒドロフラン等のエーテル系溶媒、トルエン等の芳香族系溶媒、ジメチルホルムアミド等のアミド系溶媒等が好ましい。
また、本「化合物（ＸＩＩＩ）と化合物（ＸＩＶ）とのカップリング」反応は適当な塩基を添加して行ってもよい。また、該塩基を溶媒として用いることもできる。「塩基」は前記製造法Ａで述べた「塩基」と同様なものを用いることができるが、例えば水素化ナトリウム、ナトリウムアミド、リチウムジイソプロピルアミド等が好ましい。
本「化合物（ＸＩＩＩ）と化合物（ＸＩＶ）とのカップリング」反応は、-100℃ないし300℃で行うことができるが、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし１日である。
「置換基Ｖの除去」反応は、無溶媒あるいは適当な溶媒中で行うことができる。「溶媒」は前記製造法Ａで述べた「溶媒」と同様なものを用いることができるが、例えば無溶媒、あるいはジグライム等のエーテル系溶媒、キシレン等の芳香族系溶媒、ジメチルスルホキシド等のスルホキシド系溶媒、水等が好ましい。
また、本「置換基Ｖの除去」反応は適当な酸や塩を添加して行ってもよい。また、該酸を溶媒として用いることもできる。「酸」は、例えば塩酸、硫酸等の鉱酸やｐ−トルエンスルホン酸等が好ましい。「塩」は、例えば塩化ナトリウム等が用いられる。
本「置換基Ｖの除去」反応は、好ましくは加熱して行われる。好ましくは室温ないし250℃である。反応時間は、例えば１分ないし１日である。
化合物（ＸＩＩ）は、例えばジャーナル オブ オーガニック ケミストリー(J. Org. Chem.) 36, 2480 (1971)に記載の方法に準じて製造することができる。すなわち、例えば以下に示すように、化合物（ＸＶＩ）と化合物（ＸＶＩＩ）のフリーデル−クラフツ反応により化合物（ＸＶＩＩＩ）とし、還元反応によって化合物（ＸＩＸ）に導いた後、ハロゲン化によって化合物（ＸＸ）とし、次いで分子内フリーデル−クラフツ反応を行う方法等で製造することができる。また、化合物（ＸＩＸ）の分子内フリーデル−クラフツ反応によっても製造することができる。 For example, compound (II ″) is compound (XIII) by introducing substituent V into compound (XII) as shown below, and then coupling compound (XIII) with compound (XIV) Furthermore, it can manufacture by the method etc. which remove the substituent V.

[Wherein, the substituent V is an electron-withdrawing group, Z ₃ is a leaving group, and other symbols are as defined above. ]
Examples of the “electron withdrawing group” represented by the substituent V include, for example, a C _1-8 alkoxycarbonyl group (eg, methoxycarbonyl, tert-butoxycarbonyl group, etc.), a C _7-16 aralkyloxycarbonyl group (eg, benzyloxycarbonyl). Group), a carboxyl group, a cyano group, or the like. Preferably C _1-4 alkoxycarbonyl group (e.g., methoxycarbonyl, etc. tert- butoxycarbonyl group).
As the “leaving group” represented by Z ₃ , those similar to Z ₁ can be applied. Preferably, they are a halogen atom (for example, chloro, bromo, etc.), p-toluenesulfonyloxy group or methanesulfonyloxy group.
The “introduction of substituent V” reaction can be carried out without solvent or in a suitable solvent. As the “solvent”, the same “solvent” as described in the above production method A can be used. For example, no solvent, an ether solvent such as tetrahydrofuran, an aromatic solvent such as toluene, an amide such as dimethylformamide, etc. A system solvent or the like is preferable.
As the precursor of the substituent V in this “introduction of the substituent V” reaction, for example, a carbonate ester (dimethyl carbonate or the like), a halocarbonate ester (methyl chlorocarbonate or the like), carbon dioxide or the like is used.
Further, this “introduction of substituent V” reaction may be carried out by adding an appropriate base. The base can also be used as a solvent. As the “base”, the same “base” as described in the above production method A can be used, and for example, sodium hydride, sodium amide, lithium diisopropylamide and the like are preferable.
This “introduction of substituent V” reaction can be performed at −100 ° C. to 300 ° C., preferably 0 ° C. to 150 ° C. The reaction time is, for example, 1 minute to 1 day.
The coupling reaction of compound (XIII) and compound (XIV) can be carried out without solvent or in a suitable solvent. As the “solvent”, the same “solvent” as described in the above-mentioned production method A can be used. A system solvent or the like is preferable.
Further, this “coupling of compound (XIII) and compound (XIV)” reaction may be carried out by adding an appropriate base. The base can also be used as a solvent. As the “base”, the same “base” as described in the above production method A can be used, and for example, sodium hydride, sodium amide, lithium diisopropylamide and the like are preferable.
This “coupling of compound (XIII) and compound (XIV)” reaction can be carried out at −100 ° C. to 300 ° C., preferably 0 ° C. to 150 ° C. The reaction time is, for example, 1 minute to 1 day.
The “removal of substituent V” reaction can be carried out without solvent or in a suitable solvent. As the “solvent”, the same “solvent” as described in the above production method A can be used. A system solvent, water and the like are preferable.
Further, this “removal of substituent V” reaction may be carried out by adding an appropriate acid or salt. The acid can also be used as a solvent. The “acid” is preferably a mineral acid such as hydrochloric acid or sulfuric acid, p-toluenesulfonic acid, or the like. As the “salt”, for example, sodium chloride or the like is used.
This “removal of substituent V” reaction is preferably carried out with heating. It is preferably room temperature to 250 ° C. The reaction time is, for example, 1 minute to 1 day.
Compound (XII) can be produced, for example, according to the method described in Journal of Organic Chemistry (J. Org. Chem.) 36, 2480 (1971). That is, for example, as shown below, compound (XVIII) is converted to compound (XVIII) by Friedel-Crafts reaction between compound (XVI) and compound (XVII), reduced to compound (XIX), and then compounded (XX) by halogenation. And then by a method of performing an intramolecular Friedel-Crafts reaction or the like. It can also be produced by intramolecular Friedel-Crafts reaction of compound (XIX).

[式中、各記号は前記と同意義を示す。]
「化合物（ＸＶＩ）と化合物（ＸＶＩＩ）のフリーデル−クラフツ反応」は、前記「化合物（ＩＶ）と（Ｘ）のフリーデル−クラフツ反応」に準じた方法で行うことができる。化合物（ＸＶＩＩ）から化合物（ＸＩＸ）への「還元」反応は、例えばパラジウム触媒を用いた接触還元、例えばオーガニック リアクションズ(Org. React.) 22, 401 (1975)に記載のクレメンゼン還元、例えばオーガニック リアクションズ(Org. React.) 4, 378 (1948)に記載のヴォルフ−キシュナー還元等を用いることができる。
化合物（ＸＩＸ）から化合物（ＸＸ）への「ハロゲン化」反応は、例えば塩化チオニル、オキザリルクロリド、塩素等ハロゲン化に用いられる試薬を用いて行われる。また、該ハロゲン化試薬を溶媒として用いても良い。
化合物（ＸＩＸ）から化合物（ＸＩＩ）への「分子内フリーデルクラフツ反応」は、前記「化合物（ＩＶ）と（Ｘ）のフリーデル−クラフツ反応」に準じた方法で行うことができるが、ルイス酸としてポリリン酸が好ましい。
化合物（ＸＸ）から化合物（ＸＩＩ）への「分子内フリーデルクラフツ反応」は、前記「化合物（ＩＶ）と（Ｘ）のフリーデル−クラフツ反応」に準じた方法で行うことができる。
化合物（ＸＶＩ）と化合物（ＸＸＩ）との「タンデム型分子内フリーデルクラフツ反応」による化合物（ＸＩＩ）の製造は、前記「化合物（ＩＶ）と（Ｘ）のフリーデル−クラフツ反応」に準じた方法で行うことができる。 Further, it can also be produced by a method according to, for example, Organic Synthesis Coll. Vol. 4, 898 (1963). That is, for example, as shown below, compound (XII) can be produced by a tandem intramolecular Friedel-Crafts reaction between compound (XVI) and compound (XXI).

[Wherein each symbol is as defined above. ]
The “Friedel-Crafts reaction between compound (XVI) and compound (XVII)” can be carried out by a method according to the “Friedel-Crafts reaction between compounds (IV) and (X)”. The “reduction” reaction from compound (XVII) to compound (XIX) is, for example, catalytic reduction using a palladium catalyst, for example, Clementen reduction described in Organic Reactions (Org. React.) 22, 401 (1975), for example, organic reactions. (Org. React.) 4, 378 (1948), Wolf-Kishner reduction, etc. can be used.
The “halogenation” reaction from compound (XIX) to compound (XX) is carried out using reagents used for halogenation such as thionyl chloride, oxalyl chloride, and chlorine. Further, the halogenating reagent may be used as a solvent.
The “intramolecular Friedel-Crafts reaction” from compound (XIX) to compound (XII) can be carried out by a method according to the above “Friedel-Crafts reaction of compounds (IV) and (X)”. Polyacid is preferred as the acid.
The “intramolecular Friedel-Crafts reaction” from compound (XX) to compound (XII) can be carried out by a method according to the “Friedel-Crafts reaction of compounds (IV) and (X)”.
The production of compound (XII) by the “tandem intramolecular Friedel-Crafts reaction” between compound (XVI) and compound (XXI) was in accordance with the “Friedel-Crafts reaction of compounds (IV) and (X)”. Can be done by the method.

[式中、各記号は前記と同意義を示す。]
本カップリング反応は、無溶媒あるいは適当な溶媒中で行うことができる。「溶媒」は前記製造法Ａで述べた「溶媒」と同様なものを用いることができるが、例えば無溶媒、あるいはエタノール等のアルコール系溶媒、トルエン等の芳香族系溶媒、ジメチルホルムアミド等のアミド系溶媒等が好ましい。
また、本カップリング反応は適当な塩基を添加して行ってもよい。また、該塩基を溶媒として用いることもできる。「塩基」は前記製造法Ａで述べた「塩基」と同様なものを用いることができる。
本カップリング反応の際、化合物（ＶＩ）または（ＶＩ'）の水素原子をあらかじめ金属原子、例えばリチウム、ナトリウム等のアルカリ金属等で置換しておいてもよい。
本カップリング反応は、-100℃ないし300℃で行うことができるが、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし１日である。
本カップリング反応は、化合物（ＶＩ）または（ＶＩ'）と化合物（ＶII）を任意の比率で行うことができ、さらにどちらかを溶媒として用いることもできる。
化合物（ＶII）は、それ自体公知あるいはそれに準じた方法により製造することができる。 [Production Method B] A method for producing compound (Ia), (Ic) or (Id) by a coupling reaction of compound (VI) or (VI ′) and compound (VII).

[Wherein each symbol is as defined above. ]
This coupling reaction can be carried out without solvent or in a suitable solvent. As the “solvent”, the same “solvent” as described in the above-mentioned production method A can be used. A system solvent or the like is preferable.
In addition, this coupling reaction may be performed by adding an appropriate base. The base can also be used as a solvent. As the “base”, the same “base” as described in the production method A can be used.
In this coupling reaction, the hydrogen atom of compound (VI) or (VI ′) may be substituted in advance with a metal atom, for example, an alkali metal such as lithium or sodium.
The coupling reaction can be performed at -100 ° C to 300 ° C, preferably 0 ° C to 150 ° C. The reaction time is, for example, 1 minute to 1 day.
In this coupling reaction, compound (VI) or (VI ′) and compound (VII) can be carried out at an arbitrary ratio, and either of them can be used as a solvent.
Compound (VII) can be produced by a method known per se or a method analogous thereto.

[式中、各記号は前記と同意義を示す。]
本カップリング反応は、無溶媒あるいは適当な溶媒中で行うことができる。「溶媒」は前記製造法Ａで述べた「溶媒」と同様なものを用いることができるが、例えば無溶媒、あるいはエタノール等のアルコール系溶媒、トルエン等の芳香族系溶媒、ジメチルホルムアミド等のアミド系溶媒等が好ましい。
また、本カップリング反応は適当な塩基を添加して行ってもよい。また、該塩基を溶媒として用いることもできる。「塩基」は前記製造法Ａで述べた「塩基」と同様なものを用いることができる。
本カップリング反応の際、化合物（ＶIII）の水素原子をあらかじめ金属原子、例えばリチウム、ナトリウム等のアルカリ金属等で置換しておいてもよい。
本カップリング反応は、-100℃ないし300℃で行うことができるが、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし１日である。
本カップリング反応は、化合物（II）または（II'）と化合物（ＶIII）を任意の比率で行うことができ、さらにどちらかを溶媒として用いることもできる。
化合物（ＶIII）は、それ自体公知あるいはそれに準じた方法により製造することができる。例えば、コンプリヘンシブ オーガニック トランスフォーメーション(Comprehensive Organic Transformation) VCH Publishers Inc.，1989年刊等に記載の方法、具体的にはオーガニック リアクションズ(Org. Rxs.) 14, 52 (1965)、シンセシス(Synthesis) 30 (1972) 等に記載の還元的アミノ化反応、オーガニック リアクションズ(Org. Rxs.) 6, 469 (1951)、ケミカル アンド ファーマシューティカル ブレティン（Chem. Pharm. Bull.）32, 873(1984) 等に記載のニトリルの還元反応、ジャーナル オブ メディシナル ケミストリー(J. Med. Chem.) 12, 658 (1969)、ジャーナル オブ ジ アメリカン ケミカル ソサイエティー（J. Am. Chem. Soc.） 73，5865 (1951) 等に記載のアジドの還元反応、オーガニック シンセシス(Org. Syn.) Coll. Vol. 2,83 (1943)、ジャーナル オブ ジ アメリカン ケミカル ソサイエティー（J. Am. Chem. Soc.） 72，2786 (1950) 等に記載のガブリエル合成法等によって製造することができる。 Compound (VI), (VI ′) or (VI ″) can be produced, for example, by a coupling reaction of compound (II) or (II ′) and compound (VIII) as shown below.

[Wherein each symbol is as defined above. ]
This coupling reaction can be carried out without solvent or in a suitable solvent. As the “solvent”, the same “solvent” as described in the above-mentioned production method A can be used. A system solvent or the like is preferable.
In addition, this coupling reaction may be performed by adding an appropriate base. The base can also be used as a solvent. As the “base”, the same “base” as described in the production method A can be used.
In this coupling reaction, the hydrogen atom of compound (VIII) may be substituted in advance with a metal atom, for example, an alkali metal such as lithium or sodium.
The coupling reaction can be performed at -100 ° C to 300 ° C, preferably 0 ° C to 150 ° C. The reaction time is, for example, 1 minute to 1 day.
In this coupling reaction, compound (II) or (II ′) and compound (VIII) can be carried out at an arbitrary ratio, and either of them can be used as a solvent.
Compound (VIII) can be produced by a method known per se or a method analogous thereto. For example, the method described in Comprehensive Organic Transformation VCH Publishers Inc., published in 1989, specifically Organic Reactions (Org. Rxs.) 14, 52 (1965), Synthesis 30 (1972) and other reductive amination reactions, Organic Reactions (Org. Rxs.) 6, 469 (1951), Chemical and Pharmaceutical Bulletin (Chem. Pharm. Bull.) 32, 873 (1984), etc. Nitrile reduction reactions described in Journal of Medicinal Chemistry (J. Med. Chem.) 12, 658 (1969), Journal of the American Chemical Society (J. Am. Chem. Soc.) 73, 5865 (1951), etc. Azide reduction reaction, Organic Synthesis (Org. Syn.) Coll. Vol. 2,83 (1943), Journal of the American Chemical Society (J. Am. Chem. Soc.) 72, 2786 (1950) and the like.

[式中、各記号は前記と同意義を示す。]
本カップリング反応は前記製造法Ａに準じて行うことができる。具体的には、本反応は無溶媒あるいは適当な溶媒中で行うことができる。「溶媒」は前記製造法Ａで述べた「溶媒」と同様なものを用いることができるが、例えば無溶媒、あるいはエタノール等のアルコール系溶媒、トルエン等の芳香族系溶媒、アセトニトリル等のニトリル系溶媒、ジメチルホルムアミド等のアミド系溶媒等が好ましい。
また、本カップリング反応は適当な塩基を添加して行ってもよい。また、該塩基を溶媒として用いることもできる。「塩基」は前記製造法Ａで述べた「塩基」と同様なものを用いることができるが、炭酸カリウム、トリエチルアミン、ジイソプロピルエチルアミン等が好ましい。
本カップリング反応の際、化合物（ＩＸ）の水素原子をあらかじめ金属原子、例えばリチウム、ナトリウム等のアルカリ金属等で置換しておいてもよい。
本カップリング反応は、-100℃ないし300℃で行うことができるが、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし１日である。
本カップリング反応は、化合物（ＩＸ）と化合物（ＶII）を任意の比率で行うことができ、さらにどちらかを溶媒として用いることもできる。 [Production Method C] A method for producing (Ib) by a coupling reaction of compound (IX) and compound (VII).

[Wherein each symbol is as defined above. ]
This coupling reaction can be carried out according to the above production method A. Specifically, this reaction can be carried out without solvent or in a suitable solvent. As the “solvent”, the same “solvent” as described in the above production method A can be used. Solvents and amide solvents such as dimethylformamide are preferred.
In addition, this coupling reaction may be performed by adding an appropriate base. The base can also be used as a solvent. As the “base”, the same “base” as described in the above production method A can be used, but potassium carbonate, triethylamine, diisopropylethylamine and the like are preferable.
In this coupling reaction, the hydrogen atom of compound (IX) may be substituted in advance with a metal atom, for example, an alkali metal such as lithium or sodium.
The coupling reaction can be performed at -100 ° C to 300 ° C, preferably 0 ° C to 150 ° C. The reaction time is, for example, 1 minute to 1 day.
In this coupling reaction, compound (IX) and compound (VII) can be carried out in any ratio, and either can be used as a solvent.

[式中、Ｗはアミンの保護基を、その他の各記号は前記と同意義を示す。]
アミンの保護基Ｗは、例えばプロテクティブ グループス イン オーガニック シンセシス(Protective Groups in Organic Synthesis), Third Edition, Wiley-Interscience (1999) に記載の保護基等を用いることができる。具体的には、例えば、ホルミル、置換基を有していてもよいＣ_1-6アルキル−カルボニル（例えば、アセチル、エチルカルボニル、トリフルオロアセチル、クロロアセチルなど）、ベンゾイル、Ｃ_1-6アルキル−オキシカルボニル（例えば、メトキシカルボニル、エトキシカルボニル、ｔ−ブトキシカルボニルなど）、フェニルオキシカルボニル（例えば、フェノキシカルボニルなど）、Ｃ_7-15アラルキルオキシ−カルボニル（例えば、ベンジルオキシカルボニル、フルオレニルオキシカルボニルなど）などのアシル基、あるいはトリチル、フタロイルなどの炭化水素基などが挙げられ、中でもアセチル、トリフルオロアセチル、ベンジルオキシカルボニル等が好ましい。
Ｚ₂は、好ましくは、ハロゲン原子（例えば、クロル、ブロムなど）あるいは水酸基等である。
化合物（ＩＶ）と（Ｘ）のフリーデル−クラフツ反応は、好ましくは酸触媒を添加して行うことができるが、酸触媒を添加せずに反応を行うこともできる。反応に用いられる酸触媒としては、前記化合物（II）の製造に用いた酸触媒と同様のものが用いられるが、好ましくは、ポリリン酸、塩化アルミニウム、ジエチルアルミニウムクロリド、塩化亜鉛等が挙げられる。酸触媒は、任意の当量を用いることができるが、通常、化合物（ＩＶ）あるいは化合物（Ｘ）に対して0.1当量ないし10当量である。また、場合によっては酸触媒を溶媒として用いることもできる。
溶媒は、前記化合物（II）の製造で用いた溶媒と同様のものを適用できるが、好ましくは、例えば無溶媒、あるいはジクロロメタン、１，２−ジクロロエタン等のハロゲン化炭化水素系溶媒、ニトロメタン等のニトロ化炭化水素系溶媒、ニトロベンゼン等の芳香族系溶媒、二硫化炭素等が挙げられる。
本反応は、-100℃ないし300℃で行うことができるが、通常、0℃ないし150℃が好ましい。反応時間は、例えば１分ないし３日である。
化合物（ＸＩ）の脱保護は、例えば前記プロテクティブ・グループス・イン・オーガニック・シンセシス(Protective Groups in Organic Synthesis), Third Edition, Wiley-Interscience (1999) に記載の方法等に準じて行うことができる。具体的には、酸処理、アルカリ加水分解、接触還元反応等によって実施される。
化合物（Ｘ）は、それ自体公知あるいはそれに準じた方法により製造することができる。例えば、特開平５−１４０１４９、ケミカル ファルマシューティカル ブリティン (Chem. Pharm. Bull.), 34, 3747 (1986)、ケミカル ファルマシューティカル ブリティン (Chem. Pharm. Bull.), 41, 529 (1993)、EP-A-0,378,207等に記載の方法あるいはそれに準じた方法によって製造することができる。 Compound (IX) is produced by, for example, a method of subjecting compound (XI) obtained by Friedel-Crafts reaction between compound (IV) and (X) to a deprotection reaction, as shown below, for example. Can do.

[Wherein, W represents an amine protecting group, and other symbols are as defined above.] ]
As the protecting group W of the amine, for example, a protecting group described in Protective Groups in Organic Synthesis, Third Edition, Wiley-Interscience (1999) can be used. Specifically, for example, formyl, optionally substituted C _1-6 alkyl-carbonyl (eg, acetyl, ethylcarbonyl, trifluoroacetyl, chloroacetyl, etc.), benzoyl, C _1-6 alkyl- Oxycarbonyl (eg methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl etc.), phenyloxycarbonyl (eg phenoxycarbonyl etc.), C _7-15 aralkyloxy-carbonyl (eg benzyloxycarbonyl, fluorenyloxycarbonyl etc.) ) Or a hydrocarbon group such as trityl or phthaloyl. Among them, acetyl, trifluoroacetyl, benzyloxycarbonyl and the like are preferable.
Z ₂ is preferably a halogen atom (eg, chloro, bromo, etc.) or a hydroxyl group.
The Friedel-Crafts reaction between the compounds (IV) and (X) can be preferably performed by adding an acid catalyst, but the reaction can also be performed without adding an acid catalyst. As the acid catalyst used in the reaction, those similar to the acid catalyst used in the production of the compound (II) are used, and preferred examples include polyphosphoric acid, aluminum chloride, diethylaluminum chloride, and zinc chloride. The acid catalyst can be used in any equivalent amount, and is usually 0.1 equivalent to 10 equivalents relative to compound (IV) or compound (X). In some cases, an acid catalyst can be used as a solvent.
As the solvent, the same solvents as those used in the production of the compound (II) can be applied. Preferably, for example, no solvent, halogenated hydrocarbon solvents such as dichloromethane and 1,2-dichloroethane, nitromethane and the like are used. Examples thereof include nitrated hydrocarbon solvents, aromatic solvents such as nitrobenzene, and carbon disulfide.
This reaction can be carried out at -100 ° C to 300 ° C, but usually 0 ° C to 150 ° C is preferred. The reaction time is, for example, 1 minute to 3 days.
Deprotection of compound (XI) can be carried out according to, for example, the method described in Protective Groups in Organic Synthesis, Third Edition, Wiley-Interscience (1999). . Specifically, it is carried out by acid treatment, alkali hydrolysis, catalytic reduction reaction or the like.
Compound (X) can be produced by a method known per se or a method analogous thereto. For example, Japanese Patent Application Laid-Open No. 5-140149, Chemical Pharmaceutical Bulletin (Chem. Pharm. Bull.), 34 , 3747 (1986), Chemical Pharmaceutical Bulletin (Chem. Pharm. Bull.), 41 , 529 (1993), It can be produced by the method described in EP-A-0, 378, 207 or the like or a method analogous thereto.

When the compounds (Ia) to (Id) produced by the above [Production Method A]-[Production Method C] are primary and secondary amines, they are led to other derivatives as necessary, and then isolated and purified. You can also. “Other derivatives” preferably include compounds protected by a general amine protecting group on the primary and secondary amines. Examples of the “general amine protecting group” include protecting groups described in Protective Groups in Organic Synthesis, Third Edition, Wiley-Interscience (1999). Specifically, for example, formyl, optionally substituted C _1-6 alkyl-carbonyl (eg, acetyl, ethylcarbonyl, etc.), benzoyl, C _1-6 alkyl-oxycarbonyl (eg, methoxycarbonyl) , Ethoxycarbonyl, t-butoxycarbonyl, etc.), phenyloxycarbonyl (eg, phenoxycarbonyl, etc.), C _7-15 aralkyloxy-carbonyl (eg, benzyloxycarbonyl, fluorenyloxycarbonyl, etc.) or the like, or There are hydrocarbon groups such as trityl and phthaloyl, and an acetyl group, a benzoyl group, a t-butoxycarbonyl group, a benzyloxycarbonyl group, a benzyl group and the like are preferably used. The purified “other derivatives” can be converted to the original primary and secondary amines or salts thereof by a suitable deprotection reaction. The “deprotection reaction” can be performed, for example, according to the method described in Protective Groups in Organic Synthesis, Third Edition, Wiley-Interscience (1999). Specifically, it is carried out by acid treatment, alkali hydrolysis, catalytic reduction reaction or the like.
As the “salt” of “primary and secondary amines or salts thereof”, for example, the “salt” of “when compound B is a salt” can be applied.
Compounds (Ia) to (Id) can also be produced by production methods other than those described above. For example, reduction described in Journal of the American Chemical Society (J. Am. Chem. Soc.) 2897 (1971), Synthesis 135 (1975), Tetrahedron Lett. 5595 (1990), etc. Amination reaction, Synth. Commun. 177 (1973), Tetrahedron Letters 4661 (1990) and other amine addition reactions to epoxides, Organic Reactions (Org. Rxs.) 79 (1949), Organic Synthesis (Org. Syn.) Coll. Vol. 1, 196 (1941), etc. Michael addition reaction of amine to conjugated double bond, Synthesis 752 (1978), Organic Reactions (Org Rxs.) 303 (1942) etc., reduction of amides, Organic Reactions (Org. Rxs.) 469 (1941), Angew. Chem. 265 (1956) etc. It can also be prepared by 応等.

Compound A and Compound B used in the present invention have little toxicity, show an excellent effect of improving urinary flow rate and micturition efficiency, and do not affect urinary pressure and blood pressure. It can be used as a preventive / therapeutic agent for dysuria. For example, it can be used as a prophylactic / therapeutic agent for dysuria caused by the following 1) to 7) and the like, particularly dysuria. 1) benign prostatic hyperplasia, 2) bladder neck atresia, 3) neurogenic bladder, 4) diabetes, 5) surgery, 6) hypotonic bladder, and 7) Sjogren's syndrome (dry eye, dry mouse, vaginal dryness) etc).
More specifically, hypotonic bladder due to prostatic hypertrophy, hypotonic bladder due to diabetes, hypotonic bladder due to diabetic neuropathy, idiopathic hypotonic bladder (including those due to aging), hypotonia due to multiple sclerosis Bladder, hypotonic bladder due to Parkinson's disease, hypotonic bladder due to spinal cord injury, hypotonic bladder after surgery, hypotonic bladder due to cerebral infarction, neurogenic bladder due to diabetes, neurogenic bladder due to diabetic neuropathy, multiple sclerosis It can be used as a prophylactic / therapeutic agent for dysuria due to neuropathic bladder due to infectious disease, neurogenic bladder due to Parkinson's disease, neurogenic bladder due to spinal cord injury, neurogenic bladder due to cerebral infarction, and the like.
Furthermore, Compound A and Compound B can also be used as a preventive / therapeutic agent for urinary storage disorders such as urgency due to overactive bladder, frequent urination, hypotonic bladder with overactive bladder, and urinary incontinence.
In addition, Compound A and Compound B can also be used as a prophylactic / therapeutic agent for glaucoma.

The present invention also provides a screening method for a compound having a urination disorder preventive and therapeutic action by a pressure flow study or a salt thereof, characterized by using an animal model loaded with an α agonist.
According to the screening method of the present invention, the urinary function of the bladder of the animal model (maximum urinary flow rate, intravesical pressure, micturition efficiency) of the test substance when the test substance is administered to an animal model loaded with an α agonist. Etc.) can be implemented by measuring the pressure flow study.
Examples of the “animal model” used in the screening method of the present invention include non-human mammals such as rabbits, guinea pigs, hamsters, rats, mice, gerbils, dogs and monkeys, and guinea pigs (Hartley male guinea pigs and the like) are particularly preferable. .
The age, body weight, presence / absence of delivery, etc. of the animal model used in the present invention are not particularly limited as long as they can be applied to the intended screening, but these conditions may be appropriately changed.
An animal model loaded with an alpha agonist (preferably phenylephrine) can be prepared according to known methods, for example, the methods described in Non-Patent Documents 3 to 5 above.
Examples of test substances include known synthetic compounds, peptides, proteins and the like, as well as tissue extracts and cell culture supernatants of warm-blooded mammals (eg, mice, rats, pigs, cows, sheep, monkeys, humans, etc.) Etc. are used.
The urination function (maximum urinary flow rate, intravesical pressure, urination efficiency, etc.) in the screening method of the present invention can be measured according to a known method, for example, the methods described in Non-Patent Documents 6 to 9.
The screening method of the present invention is usefully and efficiently applied to the screening of compounds having a preventive / therapeutic action for dysuria, particularly dysuria associated with benign prostatic hypertrophy, and compounds having both acetylcholinesterase inhibitory action and α1 antagonistic action. It is possible.
For example, about 0.001 to about 1000 mg / kg (preferably about 0.01 to about 100 mg / kg) of a test substance is administered to an animal model loaded with an α agonist in the screening method of the present invention, and the urinary flow rate By using the effects on the intravesical pressure, urination efficiency, etc. as indices, the therapeutic effect of the test substance can be examined to evaluate the preventive / therapeutic agent for urination disorder.
The animal model used in the present invention may be a normal animal (an animal that does not show a pathological condition). For example, dysuria, prostatic hypertrophy, hypotonic bladder, overactive bladder, frequent urination, urinary incontinence Show pathological conditions such as diabetic neuropathy, hypertension, diabetes, obesity, hyperlipidemia, arteriosclerosis, gastric ulcer, asthma, chronic obstructive respiratory disease, uterine cancer, cerebrovascular disorder, brain injury, spinal cord injury An animal (for example, an obese rat (Wistar Fatty rat) or the like) may be used to measure the urinary function of the aforementioned bladder. When measuring the urinary function of the above-described bladder in an animal exhibiting such a pathological condition, it can be effectively applied to the screening of pharmaceutical substances for the prevention and treatment of such complications. For example, the pathological condition (e.g., Drugs that are effective only for gastrointestinal diseases such as gastric ulcers, etc., and can be applied to screening for medicinal substances that do not affect urinary function, or to select test substances that do not affect urinary function It can also be applied to screening aimed at excluding substances.
By using this screening method, when the test substance is administered, the urine flow rate when administered is improved by about 20% or more, and when the urination efficiency is improved by about 10% or more, the test substance is a urinary function. Or a salt thereof (hereinafter referred to as Compound C).

Compound A, B or C can be formulated according to a method known per se. The compound itself, or a pharmacologically acceptable carrier, and a pharmacologically acceptable carrier are mixed with an appropriate amount in the formulation step, as appropriate. (Including sugar-coated tablets and film-coated tablets), powders, granules, capsules (including soft capsules), liquids, injections, suppositories, sustained-release agents, etc., orally or parenterally (eg, topical, rectal, Intravenous administration can be safely administered.
Examples of the pharmacologically acceptable carrier used in the manufacture of the medicament of the present invention, the preventive / therapeutic agent for dysuria, include various organic or inorganic carrier substances commonly used as pharmaceutical materials, such as excipients in solid formulations, Lubricants, binders, disintegrants; solvents, solubilizers, suspending agents, isotonic agents, buffers, soothing agents, etc. in liquid formulations. In addition, additives such as preservatives, antioxidants, colorants, sweeteners, adsorbents, wetting agents and the like can be used as necessary.
Examples of the excipient include lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, light anhydrous silicic acid and the like.
Examples of the lubricant include magnesium stearate, calcium stearate, talc, colloidal silica and the like.
Examples of the binder include crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, starch, sucrose, gelatin, methylcellulose, sodium carboxymethylcellulose and the like.
Examples of the disintegrant include starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch sodium, L-hydroxypropyl cellulose, and the like.
Examples of the solvent include water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil and the like.
Examples of the solubilizer include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like.
Examples of the suspending agent include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glyceryl monostearate; for example, polyvinyl alcohol, polyvinylpyrrolidone, carboxy Examples include hydrophilic polymers such as sodium methylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose.
Examples of the isotonic agent include glucose, D-sorbitol, sodium chloride, glycerin, D-mannitol and the like.
Examples of the buffer include buffer solutions such as phosphate, acetate, carbonate and citrate.
Examples of soothing agents include benzyl alcohol.
Examples of the preservative include p-hydroxybenzoates, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like.
Examples of the antioxidant include sulfite and ascorbic acid.

The content of the compound A, B or C used in the pharmaceutical agent for preventing or treating urination disorder of the present invention is about 0.1 to about 100% by weight of the whole agent.
The dose of the medicament of the present invention, the therapeutic agent for preventing urination disorder varies depending on the administration subject, administration route, disease and the like. For example, as a therapeutic agent for dysuria, 1 The active ingredient per dose is about 0.005 to 1000 mg, preferably about 0.05 to 500 mg, more preferably about 0.5 to 200 mg, which may be administered once a day or divided into several times. You can also
Compound A, B, or C is administered with a drug that treats a disease that causes dysuria (eg, dysuria, etc.) or other disease treatment, but itself causes dysuria (eg, dysuria) Can be used in combination with a drug to be used.
“Drugs that cause dysuria” include prostatic hypertrophy, prostate cancer, chronic cystitis, constipation, colon cancer, uterine cancer , Diabetes treatment, cerebrovascular disorder treatment, spinal cord injury treatment, spinal cord tumor treatment, multiple sclerosis treatment, dementia treatment including Alzheimer's disease, Parkinson's disease treatment, progression Remedies for supranuclear palsy, Guillain-Barre syndrome, acute panautonomic dysfunction, olive bridge cerebellar atrophy, cervical spondylosis and the like.

Examples of the therapeutic agent for benign prostatic hyperplasia include Allylestrenol, Chlormadinone acetate, Gestonorone caproate, Nomegestrol, Mepartricin, Finasteride, PA-109, THE-320, and the like. Examples of therapeutic agents for dysuria associated with enlarged prostate include α-reductase inhibitors such as YM-31758, YM-32906, KF-20405, MK-0434, finasteride, CS-891, and the like.
Examples of prostate cancer therapeutic agents include Ifosfamide, Estramustine phosphate sodium, Cyproterone, Chlormadinoneacetate, Flutamide, Cisplatin, Lonidamine, Peplomycin, Leuprorelin, Finasteride, Triptorelin-DDS, Buserelin, Goserelin-DDS, Fenretinide, lutine Leuprolide-DDS, Deslorelin, Cetrorelix, Ranpirnase, Leuprorelin-DDS, Satraplatin, Prinomastat, Exisulind, Buserelin-DDS, Abarelix-DDS and the like.
Examples of the therapeutic agent for chronic cystitis include Flavoxate hydrochloride.
Examples of constipation treatment include Sennoside A / B and Phenovalin.
Examples of colorectal cancer therapeutic agents include Chromomycin A3, Fluorouracil, Tegafur, Krestin, and the like.
Examples of uterine cancer therapeutic agents include Chromomycin A3, Fluorouracil, Bleomycin hydrochloride, Medroxyprogesteroneacetate and the like.
Examples of the therapeutic agent for diabetes include insulin resistance improving agent, insulin secretagogue, biguanide agent, insulin, α-glucosidase inhibitor, β3 adrenergic receptor agonist and the like.
Examples of the insulin sensitizers include pioglitazone or a salt thereof (preferably hydrochloride), troglitazone, rosiglitazone or a salt thereof (preferably maleate), JTT-501, GI-262570, MCC-555, YM-440. , DRF-2593, BM-13-1258, KRP-297, CS-011 and the like.
Examples of the insulin secretagogue include a sulfonylurea agent. Specific examples of the sulfonylurea agent include tolbutamide, chlorpropamide, tolazamide, acetohexamide, glyclopyramide and its ammonium salt, glibenclamide, gliclazide, glimepiride and the like. In addition to the above, examples of the insulin secretagogue include repaglinide, nateglinide, KAD-1229, JTT-608 and the like.
Examples of biguanides include metformin and buformin.
Examples of insulin include animal insulin extracted from bovine and porcine pancreas; semi-synthetic human insulin enzymatically synthesized from insulin extracted from porcine pancreas; human insulin synthesized by genetic engineering using Escherichia coli and yeast Etc. As insulin, insulin zinc containing 0.45 to 0.9 (w / w)% zinc; protamine insulin zinc produced from zinc chloride, protamine sulfate and insulin, and the like are also used. Furthermore, insulin may be a fragment or derivative thereof (eg, INS-1 etc.).
Examples of the α-glucosidase inhibitor include acarbose, voglibose, miglitol, emiglitate and the like.
Examples of the β3 adrenergic receptor agonist include AJ-9677, BMS-196085, SB-226552, SR-58611-A, CP-114271, L-755507, and the like.
In addition to the above, examples of the therapeutic agent for diabetes include ergoset, pramlintide, leptin, BAY-27-9955 and the like.
Etc.
Examples of cerebrovascular disorder treatments include Nicaraven, Bencyclane fumarate, Eurnamonine, Flunarizine, Nilvadipine, Ibudilast, Argatroban, Nizofenone, Naftidrofuryl, Nicergoline, Nimodipine, Papaveroline, Alteplateline, Enquisylyline, Enquisylyline , Xanthinolnicotinate, Febarbamate, Cinnarizine, Memantine, Ifenprodil, Meclofenoxatehydrochloride, Ebselen, Clopidogrel, Nebracetam, Edaravone, Clinprost-DDS, Vatanidipine, Ancrod, Dipyridamole and the like.
Examples of therapeutic agents for spinal cord injury include Methylprednisolone and Dural graft matrix.
Examples of therapeutic agents for spinal cord tumors include Nimustine hydrochloride.
Examples of the therapeutic agent for multiple sclerosis include Interferon-β-1b.
Examples of therapeutic agents for dementia including Alzheimer's disease include Aniracetam, Arginine pyroglutamate, Nefiracetam, Nimodipine, Piracetam, Propentfylline, Vinpocetine, Indeloxazine, VitaminE, Cinepazide, Memantine, Lisuride hydrogen malate, Pramiracetam, Zuclopenthix, Zuclopenthix, , Acetyl-L-carnitine, Phosphatidylserine, Nebracetam, Taltireline, Cholinealphoscerate, Ipidacrine, Talsaclidine, Cerebrolysin, Rofecoxib, ST-618, T-588, Tacrine, Physostigmine-DDS, HuperzineA, Donepezil, Trifosnate Can be mentioned.
Therapeutic agents for Parkinson's disease include, for example, Talipexole, Amantadine, Pergolide, Bromocriptine, Selegiline, Mazaticolhydrochloride, Memantine, Lisuride hydrogen malate, Trihexyphenidyl, Piroheptinhydrochloride, Terguride, Ropinirole, Ganglioside-GM1, Droleopa, Bergine, Role Pramipexole, L-dopa-methylester, Tolcapone, Remacemide, Dihydroergocryptine, Carbidopa, Selegiline-DDS, Apomorphine, Apomorphine-DDS, Etilevodopa, Levodopa and the like.
Examples of therapeutic agents for progressive supranuclear palsy include L-dopa, carbidopa, bromocriptine, pergolide, lisuride, amitriptyline, etc. It is done.
Examples of therapeutic agents for Guillain-Barre syndrome include TRH preparations such as steroids and protireline.
Examples of the therapeutic agent for acute panautonomic dysfunction include steroids, droxidopa (L-threo-DOPS), dihydroergotamine, and amezinium.
Examples of therapeutic agents for olive bridge cerebellar atrophy include TRH preparations, steroids, midodrine, and amezinium.
Examples of therapeutic agents for cervical spondylosis include anti-inflammatory sedatives.

  Examples of “drugs that are administered to treat other diseases but cause dysuria per se” include analgesics (morphine, tramadol, etc.), central skeletal muscle relaxants (baclofen, etc.), butyrophenone Antipsychotics (such as haloperidol), frequent urinary and urinary incontinence drugs (oxybutynin hydrochloride, propiverine hydrochloride, tolterodine, darifenacin, YM-905 / YM-537, temiverine (NS-21), KRP-197, trospium and other muscarinic antagonists Drugs; Smooth muscle relaxants such as flavoxate hydrochloride; Muscle relaxants such as NC-1800; Beta2 agonists such as Clenbutol; Potassium channel openers such as ZD-0947, NS-8, KW-7158, WAY-151616; ONO- PGE2 antagonists such as 8711; vanilloid receptor agonists such as resiniferatoxin and capsaicin; TAK-637, SR-48968 (saredutant), SB-223412 (talnerant), etc. Tachykinin antagonists; delta opioid agonists, etc., antispasmodics (such as butyl scopolamine bromide, butropium bromide, thikidium bromide, timepidium bromide, propanterin bromide), gastrointestinal ulcer drugs (corantil, mesafilin, cimetidine, etc.) , Parkinson's disease treatments (trihexyphenidyl hydrochloride, biperiden, masaticol hydrochloride, levodopa, etc.), antihistamines (diphenhydramine, chlorpheniramine maleate, homochlorcyclidine hydrochloride, etc.), tricyclic antidepressants (imipramine hydrochloride) , Amitriptyline hydrochloride, clomipramine hydrochloride, amoxapine, desipramine hydrochloride, etc.), phenothiazine antipsychotics (chlorpromazine, propericazine, levomepromazine, thioridazine, etc.), benzodiazepine tranquilizer / sleep Sedatives (diazepam, chlordiazepoxide, clothiazepam, estazolam, etc.), antiarrhythmic drugs (disopyramide, etc.), vasodilators (such as hydralazine hydrochloride), peripheral cerebral circulation improvers (such as pentoxifylline), bronchodilators (theophylline, ephedrine hydrochloride) , Methylephedrine hydrochloride, etc.), β-adrenergic blockers (such as propranolol hydrochloride), common cold drugs (such as Dunrich), peripheral skeletal muscle relaxants (such as dantrolene sodium), antituberculosis drugs (such as isoniazid), and the like.

When compound A, B or C is used in combination with the above-mentioned drugs for use in combination, based on the minimum recommended clinical dose of each drug, the administration subject, the age and weight of the administration subject, symptoms, administration time, administration method , Dosage form, combination of drugs and the like. The dose for a particular patient depends on age, weight, general health, sex, diet, administration time, method of administration, excretion rate, combination of drugs, and the extent of the condition being treated at the time of the patient , Determined by considering these or other factors.
Typically, the individual daily dose for a combination of Compound A, B or C and at least one compound or salt thereof selected from various disease therapeutic agents is related to the actual situation when they are administered alone. It is in the range of about 1/50 or more of the minimum recommended clinical dose and below the maximum recommended level.

The present invention is further described in detail by the following examples, formulation examples, and experimental examples, but these are not intended to limit the present invention, and may be changed without departing from the scope of the present invention.
“Room temperature” in the following Reference Examples and Examples represents 0 to 30 ° C. “%” Means weight percent unless otherwise specified.
Other abbreviations used in the text have the following meanings.
s: singlet
d: doublet
t: triplet
q: quartet
m: multiplet
br: broad
J: Coupling constant
Hz: Hertz
CDCl ₃ : deuterated chloroform DMSO-d ₆ : deuterated dimethyl sulfoxide
¹ H NMR: proton nuclear magnetic resonance (usually free form was measured in CDCl ₃ and hydrochloride was measured in DMSO-d ₆ )
IR: infrared absorption spectrum MS: mass spectrum (usually measured using an electron impact ionization method)
In the present specification and drawings, when bases, amino acids, and the like are indicated by abbreviations, they are based on abbreviations by IUPAC-IUB Commission on Biochemical Nomenclature or conventional abbreviations in the field, and examples thereof are described below. In addition, when there is an optical isomer with respect to an amino acid, the L form is shown unless otherwise specified.
DNA: deoxyribonucleic acid cDNA: complementary deoxyribonucleic acid A: adenine T: thymine G: guanine C: cytosine ATP: adenosine triphosphate EDTA: ethylenediaminetetraacetic acid

Reference example 1

1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(30.0g) および5-クロロバレリルクロリド(26.8ml) の1,2-ジクロロエタン(70ml)溶液に、水冷下、塩化アルミニウム(55g, 410mmol) を少量ずつ加えた。室温で３０分攪拌後、反応溶液を氷(500g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、エタノール−ジエチルエーテルから結晶化することにより淡黄色固形物(36.5g)を得た。さらにエタノール−ジエチルエーテルから再結晶により、表題化合物を融点110-111℃の無色結晶(32.4g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.80-2.00 (4H, m), 2.72 (2H, t, J =7.8Hz), 2.85-3.15 (4H, m), 3.23 (2H, t, J = 8.6Hz), 3.55-3.65 (2H, m), 4.14(2H, t, J = 8.6Hz), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₁₆H₁₈ClNO₂ として
計算値：C, 65.86; H, 6.22; N, 4.80.
実験値：C, 66.29; H, 6.28; N, 4.82. 8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one

1,2,5,6-Tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (30.0 g) and 5-chlorovaleryl chloride (26.8 ml) in 1,2-dichloroethane (70 ml ) Aluminum chloride (55 g, 410 mmol) was added in small portions to the solution under water cooling. After stirring at room temperature for 30 minutes, the reaction solution was poured into ice (500 g), extracted with ethyl acetate, and washed with saturated brine. After drying the organic layer with magnesium sulfate, the solvent was distilled off under reduced pressure, and crystallization from ethanol-diethyl ether gave a pale yellow solid (36.5 g). Further, recrystallization from ethanol-diethyl ether gave the title compound as colorless crystals (32.4 g) having a melting point of 110-111 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.80-2.00 (4H, m), 2.72 (2H, t, J = 7.8Hz), 2.85-3.15 (4H, m), 3.23 (2H, t, J = 8.6Hz ), 3.55-3.65 (2H, m), 4.14 (2H, t, J = 8.6Hz), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₁₆ H ₁₈ ClNO ₂ : C, 65.86; H, 6.22; N, 4.80.
Experimental values: C, 66.29; H, 6.28; N, 4.82.

Reference example 2

1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(3.00g) および6-ブロモヘキサノイルクロリド(2.91ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(3.94g)を融点97-98℃の白色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.40-1.60 (2H, m), 1.65-2.00 (4H,m), 2.72 (2H, t, J = 7.8Hz), 2.94 (2H, t, J = 7.0Hz), 3.03 (2H, t, J = 7.8Hz),3.23 (2H, t, J = 8.4Hz), 3.43 (2H, t, J = 7.0Hz), 4.14 (2H, t, J = 8.4Hz), 7.68(1H, s), 7.72 (1H, s). 8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one

Using Reference Example 1 with 1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (3.00 g) and 6-bromohexanoyl chloride (2.91 ml) The same operation was performed to obtain the title compound (3.94 g) as white crystals having a melting point of 97-98 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.40-1.60 (2H, m), 1.65-2.00 (4H, m), 2.72 (2H, t, J = 7.8Hz), 2.94 (2H, t, J = 7.0Hz ), 3.03 (2H, t, J = 7.8Hz), 3.23 (2H, t, J = 8.4Hz), 3.43 (2H, t, J = 7.0Hz), 4.14 (2H, t, J = 8.4Hz), 7.68 (1H, s), 7.72 (1H, s).

Reference example 3

5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(3.46g) および5-クロロバレリルクロリド(3.4g) を用いて、参考例１と同様の操作を行うことにより、表題化合物(3.78g)を融点89-90℃の淡黄色結晶として得た。
¹H NMR (400MHz, CDCl₃) δ 1.85-1.94 (4H, m), 2.01-2.07 (2H,m), 2.83 (2H, t, J = 6Hz), 2.96 (2H, t, J = 7Hz), 3.55 (2H, s), 3.60 (2H, d, J= 4Hz), 3.74 (2H, d, J =6 Hz), 7.73 (2H, s).
IR (KBr) νcm^-1: 1718, 1667, 1605, 1501, 1345, 1289, 1152. 8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one

Same as Reference Example 1 using 5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (3.46 g) and 5-chlorovaleryl chloride (3.4 g) The title compound (3.78 g) was obtained as pale yellow crystals having a melting point of 89-90 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.85-1.94 (4H, m), 2.01-2.07 (2H, m), 2.83 (2H, t, J = 6Hz), 2.96 (2H, t, J = 7Hz), 3.55 (2H, s), 3.60 (2H, d, J = 4Hz), 3.74 (2H, d, J = 6 Hz), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1718, 1667, 1605, 1501, 1345, 1289, 1152.

Reference example 4

5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オンおよび6-ブロモヘキサノイルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物(5.13g)を融点86-87℃の無色結晶として得た。
¹H NMR (400MHz, CDCl₃) δ 1.50-1.57 (2H, m), 1.73-1.80 (2H,m), 1.88-1.96 (2H, m), 2.01-2.07 (2H, m), 2.83 (2H, t, J = 6Hz), 2.94 (2H, t, J= 7Hz), 3.43 (2H, t, J = 7Hz), 3.56 (2H, s), 3.74 (2H, d, J = 6Hz), 7.73 (2H,s).
IR (KBr) νcm^-1: 1711, 1674, 1602, 1496, 1350, 1276, 1162. 8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one

By conducting the same operation as in Reference Example 1 using 5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and 6-bromohexanoyl chloride, the title was obtained. The compound (5.13 g) was obtained as colorless crystals having a melting point of 86-87 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.50-1.57 (2H, m), 1.73-1.80 (2H, m), 1.88-1.96 (2H, m), 2.01-2.07 (2H, m), 2.83 (2H, t, J = 6Hz), 2.94 (2H, t, J = 7Hz), 3.43 (2H, t, J = 7Hz), 3.56 (2H, s), 3.74 (2H, d, J = 6Hz), 7.73 (2H , s).
IR (KBr) νcm ^-1 : 1711, 1674, 1602, 1496, 1350, 1276, 1162.

Reference Example 5

2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび5-クロロバレリルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物(3.53g)を融点83-84℃の無色結晶として得た。
¹H NMR (400MHz, CDCl₃) δ 1.35-2.00 (6H, m), 2.68 (2H, t, J =7.5Hz), 2.85 (2H, t, J = 6Hz), 2.93-2.98 (4H, m), 3.59 (2H, t, J = 6Hz), 3.89(2H, d, J = 6Hz), 7.63 (2H, d, J = 5.3Hz).
IR (KBr) νcm^-1: 1675, 1602, 1365, 1301, 1156. 9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one

Perform the same procedure as in Reference Example 1 using 2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 5-chlorovaleryl chloride. Gave the title compound (3.53 g) as colorless crystals of melting point 83-84 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.35-2.00 (6H, m), 2.68 (2H, t, J = 7.5Hz), 2.85 (2H, t, J = 6Hz), 2.93-2.98 (4H, m) , 3.59 (2H, t, J = 6Hz), 3.89 (2H, d, J = 6Hz), 7.63 (2H, d, J = 5.3Hz).
IR (KBr) νcm ^-1 : 1675, 1602, 1365, 1301, 1156.

Reference Example 6

2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび6-ブロモヘキサノイルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物(3.90g)を融点52-53℃の無色結晶として得た。
¹H NMR (400MHz, CDCl₃) δ 1.50-1.57 (2H, m), 1.73-1.80 (2H,m), 1.89-2.00 (4H, m), 2.68 (2H, t, J = 7Hz), 2.85 (2H, t, J = 6Hz), 2.93-2.97(4H, m), 3.43 (2H, t, J = 6Hz), 3.89 (2H, d, J = 6Hz), 7.62 (2H, d, J = 5.3Hz).IR (KBr)νcm^-1: 1667, 1600, 1358, 1337, 1158. 9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one

Perform the same operation as in Reference Example 1 using 2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 6-bromohexanoyl chloride. Gave the title compound (3.90 g) as colorless crystals, mp 52-53 ° C.
_{^{1 H NMR (400MHz, CDCl 3}} ) δ 1.50-1.57 (2H, m), 1.73-1.80 (2H, m), 1.89-2.00 (4H, m), 2.68 (2H, t, J = 7Hz), 2.85 ( 2H, t, J = 6Hz), 2.93-2.97 (4H, m), 3.43 (2H, t, J = 6Hz), 3.89 (2H, d, J = 6Hz), 7.62 (2H, d, J = 5.3Hz IR (KBr) νcm ^-1 : 1667, 1600, 1358, 1337, 1158.

Reference Example 7

2H-1,4-ベンゾオキサジン-3(4H)-オン(10.0g) および5-クロロバレリルクロリド(12.5g) を用いて、参考例１と同様の操作を行うことにより、表題化合物(12.0g)を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.69-1.92 (4H, m), 2.97 (2H, t, J =6.8Hz), 3.59 (2H, t, J = 6.1Hz), 4.71 (2H, s), 7.03 (1H, d, J = 8.4Hz), 7.52(1H, d, J = 0.9Hz), 7.61 (1H, dd, J = 8.4, 2.2Hz), 8.52 (1H, s).
元素分析 C₁₃H₁₄ClNO₃ として
計算値：C, 58.32; H, 5.27; N, 5.23.
実験値：C, 58.06; H, 5.55; N, 4.96. 6- (5-Chloropentanoyl) -2H-1,4-benzoxazine-3 (4H) -one

The title compound (12.0 g) was prepared in the same manner as in Reference Example 1 using 2H-1,4-benzoxazin-3 (4H) -one (10.0 g) and 5-chlorovaleryl chloride (12.5 g). g) was obtained as colorless crystals.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.69-1.92 (4H, m), 2.97 (2H, t, J = 6.8Hz), 3.59 (2H, t, J = 6.1Hz), 4.71 (2H, s), 7.03 (1H, d, J = 8.4Hz), 7.52 (1H, d, J = 0.9Hz), 7.61 (1H, dd, J = 8.4, 2.2Hz), 8.52 (1H, s).
Elemental analysis Calculated as C ₁₃ H ₁₄ ClNO ₃ : C, 58.32; H, 5.27; N, 5.23.
Experimental value: C, 58.06; H, 5.55; N, 4.96.

Reference Example 8

2H-1,4-ベンゾオキサジン-3(4H)-オン(15.0g) および6-ブロモヘキサノイルクロリド(25.8g)を用いて、参考例１と同様の操作を行うことにより、表題化合物(14.8g)を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.50-1.58 (2H, m), 1.73-1.83 (2H,m), 1.88-1.97 (2H, m), 2.95 (2H, t, J = 4.8Hz), 3.44 (2H, t, J = 4.5Hz), 4.71(2H, s), 7.02 (1H, d, J = 5.4Hz), 7.57 (1H, d, J = 1.4Hz), 7.61 (1H, dd, J =5.6, 1.2Hz), 9.02 (1H, s).
元素分析 C₁₄H₁₆BrNO₃ として
計算値：C, 51.55; H, 4.94; N, 4.29.
実験値：C, 52.14; H, 4.87; N, 4.32.
MS m/z: 327 [M+H]⁺ 6- (6-Bromohexanoyl) -2H-1,4-benzoxazine-3 (4H) -one

The title compound (14.8) was prepared in the same manner as in Reference Example 1 using 2H-1,4-benzoxazin-3 (4H) -one (15.0 g) and 6-bromohexanoyl chloride (25.8 g). g) was obtained as colorless crystals.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.50-1.58 (2H, m), 1.73-1.83 (2H, m), 1.88-1.97 (2H, m), 2.95 (2H, t, J = 4.8Hz), 3.44 (2H, t, J = 4.5Hz), 4.71 (2H, s), 7.02 (1H, d, J = 5.4Hz), 7.57 (1H, d, J = 1.4Hz), 7.61 (1H, dd, J = 5.6, 1.2Hz), 9.02 (1H, s).
Elemental analysis Calculated as C ₁₄ H ₁₆ BrNO ₃ : C, 51.55; H, 4.94; N, 4.29.
Experimental values: C, 52.14; H, 4.87; N, 4.32.
MS m / z: 327 [M + H] ⁺

Reference Example 9

1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(4.00g) および5-クロロバレリルクロリド(9.24g) を用いて、参考例１と同様の操作を行うことにより、表題化合物(4.36g)を無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.76 (4H, m), 2.99-3.04 (2H, m),3.65-3.69 (2H, m), 7.00 (1H, d, J = 8.4Hz), 7.48 (1H, s), 7.67 (1H, dd, J =8.2, 1.4Hz), 10.88 (1H, s), 11.04 (1H, s).
MS m/z: 253 [M+H]⁺ 5- (5-Chloropentanoyl) -1,3-dihydro-2H-benzimidazol-2-one

The title compound (4.36 g) was prepared in the same manner as in Reference Example 1 using 1,3-dihydro-2H-benzimidazol-2-one (4.00 g) and 5-chlorovaleryl chloride (9.24 g). ) Was obtained as colorless crystals.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.76 (4H, m), 2.99-3.04 (2H, m), 3.65-3.69 (2H, m), 7.00 (1H, d, J = 8.4Hz), 7.48 (1H, s), 7.67 (1H, dd, J = 8.2, 1.4Hz), 10.88 (1H, s), 11.04 (1H, s).
MS m / z: 253 [M + H] ⁺

Reference Example 10

1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(3.00g) および5-クロロバレリルクロリド(5.74g) を用いて、参考例１と同様の操作を行うことにより、表題化合物(3.67g)を無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.74-1.80 (4H, m), 3.06-3.11 (2H,m), 3.38 (6H, d, J = 3.4Hz), 3.68-3.72 (2H, m), 7.26 (1H, d, J = 8.1Hz), 7.48(1H, d, J = 1.5Hz), 7.81 (1H, dd, J = 8.3, 1.7Hz). 5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one

By performing the same procedure as in Reference Example 1 using 1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one (3.00 g) and 5-chlorovaleryl chloride (5.74 g) The title compound (3.67 g) was obtained as colorless crystals.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.74-1.80 (4H, m), 3.06-3.11 (2H, m), 3.38 (6H, d, J = 3.4Hz), 3.68-3.72 (2H, m) , 7.26 (1H, d, J = 8.1Hz), 7.48 (1H, d, J = 1.5Hz), 7.81 (1H, dd, J = 8.3, 1.7Hz).

Reference Example 11

1-アセチルインドリン(1.60g) および5-クロロバレリルクロリド(1.70g) を用いて、参考例１と同様の操作を行うことにより、表題化合物(1.26g)を融点90-91℃の無色結晶として得た。
¹H NMR (400MHz, CDCl₃) δ 1.84-1.88 (4H, m), 2.26 (3H, s),2.97 (2H, t, J = 7Hz), 3.24 (2H, t, J = 8Hz), 3.58 (2H, t, J = 6Hz), 4.12 (2H,t, J = 8Hz), 7.82 (2H, br.d, J = 10Hz), 8.23 (1H, d, J = 8Hz).
IR (KBr)νcm^-1: 1666, 1603, 1488, 1442, 1398, 1336, 1235. 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one

1-acetylindoline (1.60 g) and 5-chlorovaleryl chloride (1.70 g) were used in the same manner as in Reference Example 1 to give the title compound (1.26 g) as colorless crystals having a melting point of 90-91 ° C. Got as.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.84-1.88 (4H, m), 2.26 (3H, s), 2.97 (2H, t, J = 7Hz), 3.24 (2H, t, J = 8Hz), 3.58 ( 2H, t, J = 6Hz), 4.12 (2H, t, J = 8Hz), 7.82 (2H, br.d, J = 10Hz), 8.23 (1H, d, J = 8Hz).
IR (KBr) νcm ^-1 : 1666, 1603, 1488, 1442, 1398, 1336, 1235.

Reference Example 12

1-アセチルインドリンおよび6-ブロモヘキサノイルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物(1.27g) を融点110-111℃の無色結晶として得た。
¹H NMR (400MHz, CDCl₃) δ 1.49-1.57 (2H, m), 1.72-1.79 (2H,m), 1.88-1.95 (2H, m), 2.52 (3H, s), 2.94 (2H, t, J = 7.5Hz), 3.23 (2H, t, J =8Hz), 3.42 (2H, t, J = 6Hz), 4.12 (2H, t, J = 8Hz), 7.82 (2H, br.d, J = 10Hz),8.23 (1H, d, J = 8Hz).
IR (KBr)νcm^-1: 1665, 1600, 1487, 1440, 1390, 1322, 1257. 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -6-bromo-1-hexanone

The title compound (1.27 g) was obtained as colorless crystals having a melting point of 110-111 ° C. by conducting the same operation as in Reference Example 1 using 1-acetylindoline and 6-bromohexanoyl chloride.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.49-1.57 (2H, m), 1.72-1.79 (2H, m), 1.88-1.95 (2H, m), 2.52 (3H, s), 2.94 (2H, t, J = 7.5Hz), 3.23 (2H, t, J = 8Hz), 3.42 (2H, t, J = 6Hz), 4.12 (2H, t, J = 8Hz), 7.82 (2H, br.d, J = 10Hz) ), 8.23 (1H, d, J = 8Hz).
IR (KBr) νcm ^-1 : 1665, 1600, 1487, 1440, 1390, 1322, 1257.

Reference Example 13

N-(2-メトキシフェニル)メタンスルホンアミド(10.0g) および5-クロロバレリルクロリド(7.06ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(9.15g)を無色結晶として得た。
¹H NMR(300MHz, CDCl₃) δ 1.80-1.95 (4H, m), 2.98 (2H, t, J =6.9Hz), 3.00 (3H, s), 3.58 (2H, t, J = 6.3Hz), 3.97 (3H, s), 6.58 (1H, s), 6.99(1H, d, J = 8.4Hz), 7.82 (1H, dd, J = 8.4, 1.8Hz), 8.11 (1H, d, J = 1.8Hz). N- [5- (5-Chloropentanoyl) -2-methoxyphenyl] methanesulfonamide

The title compound (9.15 g) was purified in the same manner as in Reference Example 1 using N- (2-methoxyphenyl) methanesulfonamide (10.0 g) and 5-chlorovaleryl chloride (7.06 ml). Obtained as crystals.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.80-1.95 (4H, m), 2.98 (2H, t, J = 6.9Hz), 3.00 (3H, s), 3.58 (2H, t, J = 6.3Hz), 3.97 (3H, s), 6.58 (1H, s), 6.99 (1H, d, J = 8.4Hz), 7.82 (1H, dd, J = 8.4, 1.8Hz), 8.11 (1H, d, J = 1.8Hz ).

Reference Example 14

N-(2-メトキシフェニル)メタンスルホンアミド(10.0g) および6-ブロモヘキサノイルクロリド(8.37ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(9.80g)を無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.35-1.45 (2H, m), 1.55-1.70 (2H,m), 1.75-1.90 (2H, m), 2.90-3.00 (5H, m), 3.51 (2H, t, J = 6.6Hz), 3.89 (3H,s), 7.16 (1H, d, J = 8.4Hz), 7.80-7.90 (2H, m), 9.11 (1H, s). N- [5- (6-Bromohexanoyl) -2-methoxyphenyl] methanesulfonamide

The title compound (9.80 g) was purified by the same procedure as in Reference Example 1 using N- (2-methoxyphenyl) methanesulfonamide (10.0 g) and 6-bromohexanoyl chloride (8.37 ml). Obtained as crystals.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.35-1.45 (2H, m), 1.55-1.70 (2H, m), 1.75-1.90 (2H, m), 2.90-3.00 (5H, m), 3.51 ( 2H, t, J = 6.6Hz), 3.89 (3H, s), 7.16 (1H, d, J = 8.4Hz), 7.80-7.90 (2H, m), 9.11 (1H, s).

Reference Example 15

インドール(1.00g) および5-クロロバレリルクロリド(1.68ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(1.55g) を融点165-167℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.60-1.90 (4H, m), 2.89 (2H, t, J =6.9Hz), 3.69 (2H, t, J = 6.1Hz), 7.10-7.30 (2H, m), 7.40-7.50 (1H, m),8.10-8.25 (1H, m), 8.34 (1H, d, J = 3.0Hz), 11.92 (1H, s). 5-Chloro-1- (1H-indol-3-yl) -1-pentanone

The title compound (1.55 g) was obtained as colorless crystals having a melting point of 165-167 ° C. by performing the same operation as in Reference Example 1 using indole (1.00 g) and 5-chlorovaleryl chloride (1.68 ml). .
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.60-1.90 (4H, m), 2.89 (2H, t, J = 6.9 Hz), 3.69 (2H, t, J = 6.1 Hz), 7.10-7.30 (2H , m), 7.40-7.50 (1H, m), 8.10-8.25 (1H, m), 8.34 (1H, d, J = 3.0Hz), 11.92 (1H, s).

Reference Example 16

インドール(5.00g) および6-ブロモヘキサノイルクロリド(9.95ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(9.65g) を融点150-151℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.40-1.95 (6H, m), 2.86 (2H, t, J =7.4Hz), 3.54 (2H, t, J = 6.8Hz), 7.10-7.30 (2H, m), 7.40-7.50 (1H, m),8.15-8.25 (1H, m), 8.34 (1H, d, J = 3.2Hz), 11.91 (1H, s). 6-Bromo-1- (1H-indol-3-yl) -1-hexanone

The title compound (9.65 g) was obtained as colorless crystals with a melting point of 150-151 ° C. by the same procedure as in Reference Example 1 using indole (5.00 g) and 6-bromohexanoyl chloride (9.95 ml). .
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.40-1.95 (6H, m), 2.86 (2H, t, J = 7.4Hz), 3.54 (2H, t, J = 6.8Hz), 7.10-7.30 (2H , m), 7.40-7.50 (1H, m), 8.15-8.25 (1H, m), 8.34 (1H, d, J = 3.2Hz), 11.91 (1H, s).

Reference Example 17

チオフェン(1.00ml) および5-クロロバレリルクロリド(1.63ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(2.20g) を淡黄色固形物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.80-2.00 (4H, m), 2.96 (2H, t, J =7.2Hz), 3.58 (2H, t, J = 6.3Hz), 7.14 (1H, dd, J = 5.0, 3.6Hz), 7.64 (1H, dd, J= 5.0, 1.2Hz), 7.77 (1H, dd, J = 3.6, 1.2Hz). 5-Chloro-1- (2-thienyl) -1-pentanone

The same operation as in Reference Example 1 was carried out using thiophene (1.00 ml) and 5-chlorovaleryl chloride (1.63 ml) to obtain the title compound (2.20 g) as a pale yellow solid.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.80-2.00 (4H, m), 2.96 (2H, t, J = 7.2Hz), 3.58 (2H, t, J = 6.3Hz), 7.14 (1H, dd, J = 5.0, 3.6Hz), 7.64 (1H, dd, J = 5.0, 1.2Hz), 7.77 (1H, dd, J = 3.6, 1.2Hz).

Reference Example 18

チオフェン(5ml) および6-ブロモヘキサノイルクロリド(10.5ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(12.8g) を淡赤色固形物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.40-2.00 (6H, m), 2.93 (2H, t, J =7.2Hz), 3.42 (2H, t, J = 6.8Hz), 7.13 (1H, dd, J = 5.0, 3.6Hz), 7.63 (1H, dd, J= 5.0, 1.2Hz), 7.71 (1H, dd, J = 3.6, 1.2Hz). 6-Bromo-1- (2-thienyl) -1-hexanone

The title compound (12.8 g) was obtained as a pale red solid by the same procedure as in Reference Example 1 using thiophene (5 ml) and 6-bromohexanoyl chloride (10.5 ml).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.40-2.00 (6H, m), 2.93 (2H, t, J = 7.2Hz), 3.42 (2H, t, J = 6.8Hz), 7.13 (1H, dd, J = 5.0, 3.6Hz), 7.63 (1H, dd, J = 5.0, 1.2Hz), 7.71 (1H, dd, J = 3.6, 1.2Hz).

Reference Example 19

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(3.00g) および２-フェニルエチルアミン(2.50g)の混合物を120℃ で５分間攪拌した。室温まで冷却後、反応溶液にメタノール(20ml) およびトリエチルアミン(6.89ml) を加え、次いで二炭酸ジ-t-ブチル(9.00g) のメタノール(10ml) 溶液を滴下し、室温で12時間攪拌した。溶媒を減圧下留去し、得られた残渣に水を加え、酢酸エチルで抽出した。抽出液を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；ヘキサン：酢酸エチル＝１：１)にて精製し、表題化合物を淡黄色油状物(3.00g)として得た。
¹H NMR(200MHz, CDCl₃) δ 1.44 (9H, s), 1.45-1.80 (4H, m),2.71 (2H, t, J = 7.8Hz), 2.75-3.00 (4H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.30(4H, m), 3.30-3.45 (2H, m), 4.12 (2H, t, J = 9.2Hz), 7.10-7.35 (5H, m), 7.67(1H, s), 7.71 (1H, s). 5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl (2-phenylethyl) carbamic acid tert- Butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (3.00 g) obtained in Reference Example 1 and 2- A mixture of phenylethylamine (2.50 g) was stirred at 120 ° C. for 5 minutes. After cooling to room temperature, methanol (20 ml) and triethylamine (6.89 ml) were added to the reaction solution, and then a solution of di-t-butyl dicarbonate (9.00 g) in methanol (10 ml) was added dropwise and stirred at room temperature for 12 hours. The solvent was evaporated under reduced pressure, water was added to the resulting residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; hexane: ethyl acetate = 1: 1) to obtain the title compound as a pale yellow oil (3.00 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.45-1.80 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.00 (4H, m), 3.01 (2H , t, J = 7.8Hz), 3.05-3.30 (4H, m), 3.30-3.45 (2H, m), 4.12 (2H, t, J = 9.2Hz), 7.10-7.35 (5H, m), 7.67 ( 1H, s), 7.71 (1H, s).

Reference Example 20

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(800mg) および2-(2−メトキシフェニル)エチルアミン(1.24g)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.16g) を淡黄色油状物として得た。
¹H NMR(300MHz,CDCl₃) δ 1.43 (9H, s), 1.45-1.75 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.00(4H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.30 (4H, m), 3.30-3.40 (2H, m), 3.82(3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.90 (2H, m), 7.05-7.25 (2H, m), 7.67(1H, s), 7.72 (1H, s). 2- (2-Methoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (800 mg) obtained in Reference Example 1 and 2- ( The title compound (1.16 g) was obtained as a pale yellow oil by the same procedure as in Reference Example 19 using 2-methoxyphenyl) ethylamine (1.24 g).
_{^{1 H NMR (300MHz, CDCl 3}} ) δ 1.43 (9H, s), 1.45-1.75 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.00 (4H, m), 3.01 (2H , t, J = 7.8Hz), 3.05-3.30 (4H, m), 3.30-3.40 (2H, m), 3.82 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.90 ( 2H, m), 7.05-7.25 (2H, m), 7.67 (1H, s), 7.72 (1H, s).

Reference Example 21

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(2.00g) および2-(3−メトキシフェニル)エチルアミン(3.11g)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(3.02g) を淡黄色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.45 (9H, s), 1.50-1.80 (4H, m),2.71 (2H, t, J = 7.8Hz), 2.75-3.00 (4H, m), 3.02 (2H, t, J = 7.8Hz), 3.10-3.25(4H, m), 3.30-3.45 (2H, m), 3.79 (3H, s), 4.13 (2H, t, J = 8.2Hz), 6.65-6.85(3H, m), 7.20 (1H, t, J = 7.8Hz), 7.67 (1H, s), 7.72 (1H, s). 2- (3-Methoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (2.00 g) obtained in Reference Example 1 and 2- The same operation as in Reference Example 19 was performed using (3-methoxyphenyl) ethylamine (3.11 g) to give the title compound (3.02 g) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.45 (9H, s), 1.50-1.80 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.00 (4H, m), 3.02 (2H , t, J = 7.8Hz), 3.10-3.25 (4H, m), 3.30-3.45 (2H, m), 3.79 (3H, s), 4.13 (2H, t, J = 8.2Hz), 6.65-6.85 ( 3H, m), 7.20 (1H, t, J = 7.8Hz), 7.67 (1H, s), 7.72 (1H, s).

Reference Example 22

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2-(3,4−ジメトキシフェニル)エチルアミン(930mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(408mg) を淡黄色油状物として得た。
¹H NMR(200MHz,CDCl₃) δ 1.45 (9H, s), 1.45-1.80 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.00(4H, m), 3.02 (2H, t, J = 7.8Hz), 3.05-3.30 (4H, m), 3.30-3.40 (2H, m), 3.86(3H, s), 3.87 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.65-6.85 (3H, m), 7.67 (1H,s), 7.71 (1H, s). 2- (3,4-Dimethoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl ) Pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 1 and 2- ( The same operation as in Reference Example 19 was performed using 3,4-dimethoxyphenyl) ethylamine (930 mg) to give the title compound (408 mg) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.45 (9H, s), 1.45-1.80 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.00 (4H, m), 3.02 (2H , t, J = 7.8Hz), 3.05-3.30 (4H, m), 3.30-3.40 (2H, m), 3.86 (3H, s), 3.87 (3H, s), 4.13 (2H, t, J = 8.4 Hz), 6.65-6.85 (3H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 23

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(2-クロロフェニル)エチルアミン(1.60g)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.50g) を淡黄色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.41 (9H, s), 1.50-1.80 (4H, m),2.71 (2H, t, J = 7.8Hz), 2.80-3.35 (10H, m), 3.41 (2H, t, J = 7.8Hz), 4.13 (2H,t, J = 8.2Hz), 7.00-7.40 (4H, m), 7.67 (1H, s), 7.72 (1H, s). 2- (2-Chlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The same operation as in Reference Example 19 was carried out using (2-chlorophenyl) ethylamine (1.60 g) to give the title compound (1.50 g) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.50-1.80 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.80-3.35 (10H, m), 3.41 (2H , t, J = 7.8Hz), 4.13 (2H, t, J = 8.2Hz), 7.00-7.40 (4H, m), 7.67 (1H, s), 7.72 (1H, s).

Reference Example 24

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(3-フルオロフェニル)エチルアミン(1.43g)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.40g) を淡黄色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.44 (9H, s), 1.50-1.80 (4H, m),2.71 (2H, t, J = 7.8Hz), 2.75-3.30 (10H, m), 3.39 (2H, t, J = 7.8Hz), 4.13 (2H,t, J = 8.2Hz), 6.80-7.05 (3H, m), 7.15-7.30 (1H, m), 7.68 (1H, s), 7.72 (1H,s). 2- (3-Fluorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The title compound (1.40 g) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using (3-fluorophenyl) ethylamine (1.43 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.50-1.80 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.30 (10H, m), 3.39 (2H , t, J = 7.8Hz), 4.13 (2H, t, J = 8.2Hz), 6.80-7.05 (3H, m), 7.15-7.30 (1H, m), 7.68 (1H, s), 7.72 (1H, s).

Reference Example 25

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(800mg) および2-[3-(アミノスルホニル)-4-メトキシフェニル]エチルアミン(1.89g)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(605mg) を淡黄色油状物として得た。
¹H NMR(200MHz,CDCl₃) δ 1.40-1.80 (4H, m), 1.44 (9H, s), 2.70 (2H, t, J = 7.6Hz), 2.80 (2H,t, J = 7.6Hz), 2.92 (2H, t, J = 7.4Hz), 3.02 (2H, t, J = 7.6Hz), 3.10-3.25 (2H,m), 3.22 (2H, t, J = 8.6Hz), 3.35 (2H, t, J = 7.6Hz), 3.99 (3H, s), 4.10 (2H,t, J = 8.8Hz), 5.30 (2H, s), 6.98 (1H, d, J = 8.4Hz), 7.20-7.45 (1H, m),7.60-7.75 (3H, m). 2- [3- (Aminosulfonyl) -4-methoxyphenyl] ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] Quinolin-8-yl) pentyl] carbamate tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (800 mg) obtained in Reference Example 1 and 2- [ The title compound (605 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using 3- (aminosulfonyl) -4-methoxyphenyl] ethylamine (1.89 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.40-1.80 (4H, m), 1.44 (9H, s), 2.70 (2H, t, J = 7.6Hz), 2.80 (2H, t, J = 7.6Hz), 2.92 (2H, t, J = 7.4Hz), 3.02 (2H, t, J = 7.6Hz), 3.10-3.25 (2H, m), 3.22 (2H, t, J = 8.6Hz), 3.35 (2H, t , J = 7.6Hz), 3.99 (3H, s), 4.10 (2H, t, J = 8.8Hz), 5.30 (2H, s), 6.98 (1H, d, J = 8.4Hz), 7.20-7.45 (1H , m), 7.60-7.75 (3H, m).

Reference Example 26

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2-(2-メトキシフェニル)-1-メチルエチルアミン(848mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(641mg) を淡黄色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.19 (3H, d, J = 7.0Hz), 1.30-2.00(9H. m), 1.37 (9H, s), 2.71 (2H, t, J = 7.6Hz), 2.80-3.10 (6H, m), 3.22 (2H, t,J = 8.4Hz), 3.82 (3H, s), 4.13 (2H, t, J = 8.8Hz), 6.75-7.20 (2H, m), 7.67 (1H,s), 7.71 (1H, s). 2- (2-methoxyphenyl) -1-methylethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8 -Yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 1 and 2- ( The title compound (641 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using 2-methoxyphenyl) -1-methylethylamine (848 mg).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.19 (3H, d, J = 7.0Hz), 1.30-2.00 (9H.m), 1.37 (9H, s), 2.71 (2H, t, J = 7.6Hz), 2.80-3.10 (6H, m), 3.22 (2H, t, J = 8.4Hz), 3.82 (3H, s), 4.13 (2H, t, J = 8.8Hz), 6.75-7.20 (2H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 27

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および２-フェニルエチルアミン(0.538ml)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(450mg) を淡黄色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.25-1.60 (4H, m), 1.44 (9H, s),1.65-1.80 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.90 (2H, m), 2.90 (2H, t, J =7.5Hz), 3.01 (2H, t, J = 7.5Hz), 3.05-3.45 (4H, m), 3.22 (2H, t, J = 8.4Hz),4.12 (2H, t, J = 8.4Hz), 7.10-7.35 (5H, m), 7.67 (1H, s), 7.71 (1H, s). 6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl (2-phenylethyl) carbamic acid tert- Butyl

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 2-phenyl obtained in Reference Example 2 The title compound (450 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using ethylamine (0.538 ml).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.60 (4H, m), 1.44 (9H, s), 1.65-1.80 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.90 (2H, m), 2.90 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 7.5Hz), 3.05-3.45 (4H, m), 3.22 (2H, t, J = 8.4Hz) , 4.12 (2H, t, J = 8.4Hz), 7.10-7.35 (5H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 28

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.50g) および2-(2−メトキシフェニル)エチルアミン(1.94g)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.51g) を淡黄色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.25-1.60 (4H, m), 1.43 (9H, s),1.65-1.80 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.90 (2H, m), 2.90 (2H, t, J =7.5Hz), 3.01 (2H, t, J = 7.5Hz), 3.05-3.45 (6H, m), 3.82 (3H, s), 4.12 (2H, t,J = 8.4Hz), 6.80-6.90 (2H, m), 7.00-7.20 (2H, m), 7.67 (1H, s), 7.71 (1H, s). 2- (2-Methoxyphenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl ] Tert-butyl carbamate

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.50 g) obtained in Reference Example 2 and 2- The same operation as in Reference Example 19 was performed using (2-methoxyphenyl) ethylamine (1.94 g) to give the title compound (1.51 g) as a pale yellow oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.60 (4H, m), 1.43 (9H, s), 1.65-1.80 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.90 (2H, m), 2.90 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 7.5Hz), 3.05-3.45 (6H, m), 3.82 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.90 (2H, m), 7.00-7.20 (2H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 29

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2-(3−メトキシフェニル)エチルアミン(650mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(562mg) を淡黄色油状物として得た。
¹H NMR(300MHz,CDCl₃) δ 1.25-1.60 (4H, m), 1.45 (9H, s), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.71(2H, t, J = 7.8Hz), 2.75-2.85 (2H, m), 2.90 (2H, t, J = 7.5Hz), 3.01 (2H, t, J= 7.8Hz), 3.05-3.45 (4H, m), 3.22 (2H, t, J = 8.4Hz), 3.79 (3H, s), 4.12 (2H,t, J = 8.4Hz), 6.70-6.85 (3H, m), 7.20 (1H, t, J = 7.8Hz), 7.67 (1H, s), 7.71(1H, s). 2- (3-Methoxyphenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl ] Tert-butyl carbamate

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and 2- ( The same operation as in Reference Example 19 was carried out using 3-methoxyphenyl) ethylamine (650 mg) to obtain the title compound (562 mg) as a pale yellow oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.60 (4H, m), 1.45 (9H, s), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.71 (2H, t, J = 7.8Hz ), 2.75-2.85 (2H, m), 2.90 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 7.8Hz), 3.05-3.45 (4H, m), 3.22 (2H, t, J = 8.4Hz), 3.79 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.70-6.85 (3H, m), 7.20 (1H, t, J = 7.8Hz), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 30

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) および2-(4−メトキシフェニル)エチルアミン(907mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(900mg) を淡黄色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.25-1.55 (4H, m), 1.41 (9H, s),1.60-1.75 (2H, m), 2.60-2.75 (4H, m), 2.85 (2H, t, J = 7.5Hz), 2.97 (2H, t, J =7.8Hz), 3.00-3.35 (4H, m), 3.17 (2H, t, J = 8.4Hz), 3.74 (3H, s), 4.08 (2H, t,J = 8.4Hz), 6.75-6.80 (2H, m), 7.00-7.10 (2H, m), 7.63 (1H, s), 7.67 (1H, s). 2- (4-Methoxyphenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl ] Tert-butyl carbamate

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) obtained in Reference Example 2 and 2- ( The title compound (900 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using 4-methoxyphenyl) ethylamine (907 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.55 (4H, m), 1.41 (9H, s), 1.60-1.75 (2H, m), 2.60-2.75 (4H, m), 2.85 (2H, t, J = 7.5Hz), 2.97 (2H, t, J = 7.8Hz), 3.00-3.35 (4H, m), 3.17 (2H, t, J = 8.4Hz), 3.74 (3H, s), 4.08 (2H, t, J = 8.4Hz), 6.75-6.80 (2H, m), 7.00-7.10 (2H, m), 7.63 (1H, s), 7.67 (1H, s).

Reference Example 31

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2-(2−クロロフェニル)エチルアミン(430mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(540mg) を淡黄色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.25-1.60 (4H, m), 1.41 (9H, s),1.65-1.80 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.85-3.30 (4H, m), 2.89 (2H, t, J =7.5Hz), 3.01 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.39 (2H, t, J =7.5Hz), 4.12 (2H, t, J = 8.4Hz), 7.10-7.35 (4H, m), 7.67 (1H, s), 7.71 (1H, s). 2- (2-Chlorophenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl] Tert-butyl carbamate

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and 2- ( The title compound (540 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using 2-chlorophenyl) ethylamine (430 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.60 (4H, m), 1.41 (9H, s), 1.65-1.80 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.85-3.30 (4H, m), 2.89 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.39 (2H, t, J = 7.5Hz), 4.12 (2H, t, J = 8.4Hz), 7.10-7.35 (4H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 32

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2-(3−フルオロフェニル)エチルアミン(600mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(613mg) を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.25-1.60 (4H, m), 1.44 (9H, s),1.74 (2H, tt, J = 7.5, 7.5Hz), 2.71 (2H, t, J = 7.5Hz), 2.75-2.90 (2H, m), 2.90(2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.05-3.45 (2H, m), 3.22 (2H, t, J= 8.4Hz), 3.37 (2H, t, J = 7.5Hz), 4.13 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m),7.20-7.30 (1H, m), 7.67 (1H, s), 7.71 (1H, s). 2- (3-Fluorophenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl ] Tert-butyl carbamate

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and 2- ( The title compound (613 mg) was obtained as a colorless oil by the same operation as in Reference Example 19 using 3-fluorophenyl) ethylamine (600 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.60 (4H, m), 1.44 (9H, s), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.71 (2H, t, J = 7.5Hz ), 2.75-2.90 (2H, m), 2.90 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.05-3.45 (2H, m), 3.22 (2H, t, J = 8.4Hz), 3.37 (2H, t, J = 7.5Hz), 4.13 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m), 7.20-7.30 (1H, m), 7.67 ( 1H, s), 7.71 (1H, s).

Reference Example 33

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および2-(2-メトキシフェニル)-1-メチルエチルアミン(850mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(467mg) を淡黄色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.18 (3H, d, J = 6.9Hz), 1.25-1.90(6H, m), 1.36 (9H, s), 2.71 (2H, t, J = 7.5Hz), 2.75-3.20 (5H, m), 2.88 (2H, t,J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.82 (3H, s),4.13 (2H, t, J = 8.4Hz), 6.80-7.25 (4H, m), 7.67 (1H, s), 7.72 (1H, s). 2- (2-methoxyphenyl) -1-methylethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8 -Il) hexyl] carbamate tert-butyl

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) obtained in Reference Example 2 and 2- ( The title compound (467 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using 2-methoxyphenyl) -1-methylethylamine (850 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.18 (3H, d, J = 6.9Hz), 1.25-1.90 (6H, m), 1.36 (9H, s), 2.71 (2H, t, J = 7.5Hz), 2.75-3.20 (5H, m), 2.88 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.82 (3H, s ), 4.13 (2H, t, J = 8.4Hz), 6.80-7.25 (4H, m), 7.67 (1H, s), 7.72 (1H, s).

Reference Example 34

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および3-フェニル-1-プロピルアミン(694mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(660mg) を淡黄色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.20-2.00 (6H, m), 1.43 (9H, s), 2.60(2H, t, J = 7.8Hz), 2.71 (2H, t, J = 7.5Hz), 2.93 (2H, t, J = 7.5Hz), 3.01 (2H,t, J = 7.8Hz), 3.10-3.40 (6H, m), 4.13 (2H, t, J = 8.4Hz), 7.10-7.35 (5H, m),7.67 (1H, s), 7.71 (1H, s). 5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl (3-phenylpropyl) carbamic acid tert- Butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 3-phenyl obtained in Reference Example 1 The title compound (660 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using -1-propylamine (694 mg).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-2.00 (6H, m), 1.43 (9H, s), 2.60 (2H, t, J = 7.8Hz), 2.71 (2H, t, J = 7.5Hz), 2.93 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 7.8Hz), 3.10-3.40 (6H, m), 4.13 (2H, t, J = 8.4Hz), 7.10-7.35 (5H , m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 35

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) および3-フェニル-1-プロピルアミン(811mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(906mg) を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.20-1.60 (4H, m), 1.44 (9H, s),1.74 (2H, tt, J = 7.5, 7.5Hz), 1.84 (2H, tt, J = 7.5, 7.5Hz), 2.59 (2H, t, J =7.8Hz), 2.71 (2H, t, J = 7.5Hz), 2.90 (2H, t, J = 7.5Hz), 3.02 (2H, t, J =7.8Hz), 3.10-3.30 (6H, m), 4.12 (2H, t, J = 8.4Hz), 7.10-7.30 (5H, m), 7.67(1H, s), 7.72 (1H, s). 6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl (3-phenylpropyl) carbamic acid tert- Butyl

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) and 3-phenyl obtained in Reference Example 2 The title compound (906 mg) was obtained as a colorless oil by the same procedures as in Reference Example 19 using -1-propylamine (811 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.20-1.60 (4H, m), 1.44 (9H, s), 1.74 (2H, tt, J = 7.5, 7.5Hz), 1.84 (2H, tt, J = 7.5, 7.5Hz), 2.59 (2H, t, J = 7.8Hz), 2.71 (2H, t, J = 7.5Hz), 2.90 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz) ), 3.10-3.30 (6H, m), 4.12 (2H, t, J = 8.4Hz), 7.10-7.30 (5H, m), 7.67 (1H, s), 7.72 (1H, s).

Reference Example 36

参考例３で得た8-(5-クロロペンタノイル)-5, 6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(293mg) および2-(2−メトキシフェニル)エチルアミン(378mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(86mg) を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43 (9H, s), 1.51-1.76 (4H, m),2.00-2.07 (2H, m), 2.81 (4H, t, J = 6Hz), 2.88-2.96 (2H, m), 3.10-3.25 (2H, m),3.32-3.41 (2H, m), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 3.82 (3H, s), 6.83-6.89(2H, m), 7.09-7.21 (2H, m), 7.73 (2H, s). 2- (2-Methoxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (293 mg) and 2- (2) obtained in Reference Example 3 The title compound (86 mg) was obtained as a pale yellow oil by the same procedures as in Reference Example 19 using -methoxyphenyl) ethylamine (378 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.76 (4H, m), 2.00-2.07 (2H, m), 2.81 (4H, t, J = 6Hz), 2.88-2.96 ( 2H, m), 3.10-3.25 (2H, m), 3.32-3.41 (2H, m), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 3.82 (3H, s), 6.83- 6.89 (2H, m), 7.09-7.21 (2H, m), 7.73 (2H, s).

Reference Example 37

参考例３で得た8-(5-クロロペンタノイル)-5, 6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよび2-(2−クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物(147mg)を淡黄色油状物として得た
¹H NMR(400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.76 (4H, m),2.00-2.06 (2H, m), 2.82 (2H, t, J = 6Hz), 2.87-3.00 (4H, m), 3.10-3.26 (2H, m),3.41 (2H, t, J = 7Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.13-7.24 (3H, m),7.33 (1H, d, J = 7.2Hz), 7.73 (2H, s). 2- (2-Chlorophenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl] Tert-butyl carbamate

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and 2- (2-chlorophenyl) obtained in Reference Example 3 The title compound (147 mg) was obtained as a pale yellow oil by the same operation as in Reference Example 19 using ethylamine.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.76 (4H, m), 2.00-2.06 (2H, m), 2.82 (2H, t, J = 6Hz), 2.87-3.00 ( 4H, m), 3.10-3.26 (2H, m), 3.41 (2H, t, J = 7Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.13-7.24 (3H, m ), 7.33 (1H, d, J = 7.2Hz), 7.73 (2H, s).

Reference Example 38

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび２-フェニルエチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物(320mg)を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.44 (9H, s), 1.51-1.75 (4H, m),1.93-1.99 (2H, m), 2.67 (2H, t, J = 6Hz), 2.82-2.85 (4H, m), 2.92-2.95 (4H, m),3.12-3.24 (2H, m),3.32-3.42 (2H, m), 3.89 (2H, t, J = 6Hz), 7.18-7.30 (5H, m),7.61 (2H, d, J = 5Hz). 5-oxo-5- (3-oxo-2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-9-yl) pentyl (2-phenylethyl) carbamic acid tert-butyl

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 2-phenylethylamine obtained in Reference Example 5 Was used for the same operation as in Reference Example 19 to give the title compound (320 mg) as a pale-yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.51-1.75 (4H, m), 1.93-1.99 (2H, m), 2.67 (2H, t, J = 6Hz), 2.82-2.85 ( 4H, m), 2.92-2.95 (4H, m), 3.12-3.24 (2H, m), 3.32-3.42 (2H, m), 3.89 (2H, t, J = 6Hz), 7.18-7.30 (5H, m ), 7.61 (2H, d, J = 5Hz).

Reference Example 39

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび2-(2−メトキシフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物(414mg)を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43 (9H, s), 1.51-1.76 (4H, m),1.93-1.99 (2H, m), 2.67 (2H, t, J = 6Hz), 2.82-2.85 (4H, m), 2.91-2.95 (4H, m),3.13-3.25 (2H, m), 3.31-3.42 (2H, m), 3.82 (3H, s), 3.89 (2H, t, J = 6Hz),6.83-6.89 (2H, m), 7.07-7.21 (2H, m), 7.61 (2H, d, J = 5Hz). 2- (2-Methoxyphenyl) ethyl [5-oxo-5- (3-oxo-2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-9-yl ) Pentyl] carbamic acid tert-butyl

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 2- (2 The title compound (414 mg) was obtained as a pale yellow oil by the same procedures as in Reference Example 19 using -methoxyphenyl) ethylamine.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.76 (4H, m), 1.93-1.99 (2H, m), 2.67 (2H, t, J = 6Hz), 2.82-2.85 ( 4H, m), 2.91-2.95 (4H, m), 3.13-3.25 (2H, m), 3.31-3.42 (2H, m), 3.82 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.07-7.21 (2H, m), 7.61 (2H, d, J = 5Hz).

Reference Example 40

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび2-(2−クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物(385mg)を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.76 (4H, m),1.93-1.99 (2H, m), 2.67 (2H, t, J = 6Hz), 2.84 (2H, t, J = 6Hz), 2.94 (6H, t, J= 6.8Hz), 3.12-3.26 (2H, m), 3.41 (2H, t, J = 7Hz), 3.89 (2H, t, J = 6Hz),7.13-7.19 (3H, m), 7.33 (1H, d, J = 7.2Hz), 7.62 (2H, d, J = 5Hz). 2- (2-Chlorophenyl) ethyl [5-oxo-5- (3-oxo-2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-9-yl) Pentyl] carbamic acid tert-butyl

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 2- (2 The title compound (385 mg) was obtained as a pale yellow oil by the same procedures as in Reference Example 19 using -chlorophenyl) ethylamine.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.76 (4H, m), 1.93-1.99 (2H, m), 2.67 (2H, t, J = 6Hz), 2.84 (2H, t, J = 6Hz), 2.94 (6H, t, J = 6.8Hz), 3.12-3.26 (2H, m), 3.41 (2H, t, J = 7Hz), 3.89 (2H, t, J = 6Hz), 7.13-7.19 (3H, m), 7.33 (1H, d, J = 7.2Hz), 7.62 (2H, d, J = 5Hz).

Reference Example 41

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-フェニルエチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.44 (9H, m), 1.58 (2H, m),1.65-1.75 (2H, m), 2.81 (2H, m), 2.90-2.94 (2H, m), 3.15-3.22 (2H, m), 3.37(2H, m), 4.69 (2H, s), 6.99 (1H, d, J = 8.4Hz), 7.16-7.30 (5H, m), 7.58-7.61(2H, m), 9.36
(1H, s). 5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl (2-phenylethyl) carbamate tert-butyl

Perform the same operations as in Reference Example 19 using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2-phenylethylamine obtained in Reference Example 7. Gave the title compound as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.44 (9H, m), 1.58 (2H, m), 1.65-1.75 (2H, m), 2.81 (2H, m), 2.90-2.94 (2H, m), 3.15 -3.22 (2H, m), 3.37 (2H, m), 4.69 (2H, s), 6.99 (1H, d, J = 8.4Hz), 7.16-7.30 (5H, m), 7.58-7.61 (2H, m ), 9.36
(1H, s).

Reference Example 42

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(2-エトキシフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.42 (3H, t, J = 6.4Hz), 1.44 (9H,s), 1.60-1.73 (4H, m), 2.83-2.94 (4H, m), 3.18-3.36 (4H, m), 3.99-4.06 (2H, m),4.68 (2H, s), 6.80-6.87 (2H, m), 6.96-6.99 (1H, d, J = 6.6Hz), 7.07-7.18 (2H,m), 7.58-7.63 (2H, m), 9.67 (1H, s). 2- (2-Ethoxyphenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert-butyl

Similar to Reference Example 19 using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (2-ethoxyphenyl) ethylamine obtained in Reference Example 7. To give the title compound as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.42 (3H, t, J = 6.4Hz), 1.44 (9H, s), 1.60-1.73 (4H, m), 2.83-2.94 (4H, m), 3.18-3.36 (4H, m), 3.99-4.06 (2H, m), 4.68 (2H, s), 6.80-6.87 (2H, m), 6.96-6.99 (1H, d, J = 6.6Hz), 7.07-7.18 (2H , m), 7.58-7.63 (2H, m), 9.67 (1H, s).

Reference Example 43

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(2-フルオロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.42 (9H, m), 1.52-1.78 (4H, m),2.82-2.96 (4H, m), 3.25 (2H, m), 3.36-3.43 (2H, m), 4.69 (2H, s), 6.96-7.08(3H, m), 7.14-7.23 (2H, m), 7.58-7.63 (2H, m), 9.16 (1H, s). 2- (2-Fluorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert-butyl

Similar to Reference Example 19 using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (2-fluorophenyl) ethylamine obtained in Reference Example 7. To give the title compound as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.42 (9H, m), 1.52-1.78 (4H, m), 2.82-2.96 (4H, m), 3.25 (2H, m), 3.36-3.43 (2H, m) , 4.69 (2H, s), 6.96-7.08 (3H, m), 7.14-7.23 (2H, m), 7.58-7.63 (2H, m), 9.16 (1H, s).

Reference Example 44

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.42 (9H, m), 1.67 (4H, m), 2.92(4H, m), 3.25 (2H, m), 3.37-3.45 (2H, m), 4.69 (2H, s), 6.99 (1H, d, J =8.8Hz), 7.17 (3H, m), 7.30-7.34 (1H, m), 7.61-7.62 (2H, m), 9.56 (1H, s). 2- (2-Chlorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert-butyl

Using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 7, the same as in Reference Example 19 By performing the operation, the title compound was obtained as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.42 (9H, m), 1.67 (4H, m), 2.92 (4H, m), 3.25 (2H, m), 3.37-3.45 (2H, m), 4.69 (2H , s), 6.99 (1H, d, J = 8.8Hz), 7.17 (3H, m), 7.30-7.34 (1H, m), 7.61-7.62 (2H, m), 9.56 (1H, s).

Reference Example 45

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(3-メトキシフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.45 (9H, m), 1.55-1.77 (4H, m), 2.75-2.82(2H, m), 2.88-2.95 (2H, m), 3.22 (2H, m), 3.37 (2H, m), 3.79 (3H, s), 4.69 (2H,s), 6.73-6.78 (3H, m), 6.99 (1H, d, J = 8.8Hz), 7.16-7.23 (1H, m), 7.58-7.62(2H, m), 9.46 (1H, s). 2- (3-Methoxyphenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert-butyl

Similar to Reference Example 19 using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (3-methoxyphenyl) ethylamine obtained in Reference Example 7. To give the title compound as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.45 (9H, m), 1.55-1.77 (4H, m), 2.75-2.82 (2H, m), 2.88-2.95 (2H, m), 3.22 (2H, m) , 3.37 (2H, m), 3.79 (3H, s), 4.69 (2H, s), 6.73-6.78 (3H, m), 6.99 (1H, d, J = 8.8Hz), 7.16-7.23 (1H, m ), 7.58-7.62 (2H, m), 9.46 (1H, s).

Reference Example 46

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(3-エトキシフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.40 (3H, t, J = 7.0Hz), 1.45 (9H,s), 1.55-1.77 (4H, m), 2.74-2.81 (2H, m), 2.88-2.95 (2H, m), 3.21 (2H, m), 3.36(2H, m), 4.01 (2H, q, J = 7Hz), 4.69 (2H, s), 6.72-6.76 (3H, m), 6.99 (1H, d, J= 8.8Hz), 7.14-7.22 (1H, m), 7.58-7.62 (2H, m), 9.43 (1H, s). 2- (3-Ethoxyphenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert-butyl

Similar to Reference Example 19 using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (3-ethoxyphenyl) ethylamine obtained in Reference Example 7. To give the title compound as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.40 (3H, t, J = 7.0Hz), 1.45 (9H, s), 1.55-1.77 (4H, m), 2.74-2.81 (2H, m), 2.88-2.95 (2H, m), 3.21 (2H, m), 3.36 (2H, m), 4.01 (2H, q, J = 7Hz), 4.69 (2H, s), 6.72-6.76 (3H, m), 6.99 (1H , d, J = 8.8Hz), 7.14-7.22 (1H, m), 7.58-7.62 (2H, m), 9.43 (1H, s).

Reference Example 47

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(280mg) および2-(2-メトキシフェニル)エチルアミン(378mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(170mg) を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43 (9H, s), 1.51-1.72 (4H, m),2.22 (3H, s), 2.75-2.88 (2H, m), 2.90-2.95 (2H, m), 3.08-3.22 (4H, m),3.32-3.41 (2H, m), 3.81 (3H, s), 4.07 (2H, t, J = 7Hz), 6.81-6.87 (2H, m),7.08-7.19 (2H, m), 7.77-7.81 (2H, m), 8.21 (1H, d, J = 8.5Hz). 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (280 mg) and 2- (2-methoxyphenyl) ethylamine (280 mg) obtained in Reference Example 11 378 mg) was used for the same operation as in Reference Example 19 to give the titled compound (170 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.72 (4H, m), 2.22 (3H, s), 2.75-2.88 (2H, m), 2.90-2.95 (2H, m) , 3.08-3.22 (4H, m), 3.32-3.41 (2H, m), 3.81 (3H, s), 4.07 (2H, t, J = 7Hz), 6.81-6.87 (2H, m), 7.08-7.19 ( 2H, m), 7.77-7.81 (2H, m), 8.21 (1H, d, J = 8.5Hz).

Reference Example 48

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(560mg) および２-フェニルエチルアミン(606mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(290mg) を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.44(9H, s), 1.51-1.74(4H, m), 2.25(3H, s), 2.75-2.88(2H, m), 2.89-2.96(2H, m), 3.05-3.27(4H, m), 3.30-3.43(2H, m), 4.11(2H, t, J = 7.3Hz), 7.15-7.30(5H, m), 7.79-7.83(2H, m), 8.22(1H, d, J = 8.5Hz). 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl (2-phenylethyl) carbamate tert-butyl

Using 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (560 mg) and 2-phenylethylamine (606 mg) obtained in Reference Example 11 The title compound (290 mg) was obtained as a pale yellow oil by the same operations as in Reference Example 19.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.51-1.74 (4H, m), 2.25 (3H, s), 2.75-2.88 (2H, m), 2.89-2.96 (2H, m) , 3.05-3.27 (4H, m), 3.30-3.43 (2H, m), 4.11 (2H, t, J = 7.3Hz), 7.15-7.30 (5H, m), 7.79-7.83 (2H, m), 8.22 (1H, d, J = 8.5Hz).

Reference Example 49

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.41(9H, s), 1.51-1.76(4H, m), 2.25(3H, s), 2.94(4H, br.s), 3.12(2H, br.s), 3.22(2H, t, J = 7.6Hz), 3.41(2H, t, J = 7Hz), 4.11(2H, t, J = 7.3Hz), 7.17(3H, br.s), 7.33(1H, d, J = 7.2Hz), 7.79-7.83(2H, m), 8.22(1H, d, J = 8.5Hz). Tert-Butyl 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate

Using 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 11, The same operation as in Example 19 was carried out to give the title compound as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.76 (4H, m), 2.25 (3H, s), 2.94 (4H, br.s), 3.12 (2H, br.s) , 3.22 (2H, t, J = 7.6Hz), 3.41 (2H, t, J = 7Hz), 4.11 (2H, t, J = 7.3Hz), 7.17 (3H, br.s), 7.33 (1H, d , J = 7.2Hz), 7.79-7.83 (2H, m), 8.22 (1H, d, J = 8.5Hz).

Reference Example 50

参考例４７で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(1.00g) に水酸化カリウム(0.22g) のメタノール(4ml) 溶液を室温で加え、攪拌しながら2時間加熱還流した。溶媒を減圧下留去し、得られた残渣に水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；ヘキサン：酢酸エチル＝１：１)にて精製し、表題化合物を淡黄色油状物(700mg)として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43(9H, s), 1.51-1.72(4H, m), 2.78-2.88(4H, m), 3.06(2H, t, J = 8.5Hz), 3.08-3.24(2H, m), 3.32-3.39(2H, m), 3.65(2H, t, J = 8.5Hz), 3.81(3H, s), 4.26(1H, br.s), 6.52(1H, d, J = 8Hz), 6.82-6.88(2H, m), 7.08-7.20(2H, m), 7.69(1H, d. J = 8Hz), 7.72(1H, s). Tert-Butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate

Tert-butyl 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 47 (1.00 A solution of potassium hydroxide (0.22 g) in methanol (4 ml) was added to g) at room temperature, and the mixture was heated to reflux with stirring for 2 hours. The solvent was evaporated under reduced pressure, water was added to the resulting residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; hexane: ethyl acetate = 1: 1) to give the title compound as a pale yellow oil (700 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.72 (4H, m), 2.78-2.88 (4H, m), 3.06 (2H, t, J = 8.5Hz), 3.08-3.24 (2H, m), 3.32-3.39 (2H, m), 3.65 (2H, t, J = 8.5Hz), 3.81 (3H, s), 4.26 (1H, br.s), 6.52 (1H, d, J = 8Hz), 6.82-6.88 (2H, m), 7.08-7.20 (2H, m), 7.69 (1H, d.J = 8Hz), 7.72 (1H, s).

Reference Example 51

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(362mg) のジメチルホルムアミド(2ml) 溶液に炭酸カリウム(166mg) およびヨウ化メチル(170mg) を加え、60-70℃で5時間攪拌した。溶媒を減圧下留去し、得られた残渣に水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；ヘキサン：酢酸エチル＝１：１)にて精製し、表題化合物を淡黄色油状物(125mg)として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43(9H, s), 1.51-1.70(4H, m), 2.78-2.88(4H, m), 2.84(3H, s), 3.00(2H, t, J = 8.5Hz), 3.08-3.24(2H, m), 3.31-3.40(2H, m), 3.48(2H, t, J = 8.5Hz), 3.81(3H, s), 6.34(1H, d, J = 8Hz), 6.82-6.88(2H, m), 7.08-7.20(2H, m), 7.67(1H, s), 7.76(1H, d, J = 8Hz). 5- (2,3-Dihydro-1-methyl-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Dimethylformamide of tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate (362 mg) obtained in Reference Example 50 (2 ml) To the solution were added potassium carbonate (166 mg) and methyl iodide (170 mg), and the mixture was stirred at 60-70 ° C. for 5 hours. The solvent was evaporated under reduced pressure, water was added to the resulting residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; hexane: ethyl acetate = 1: 1) to obtain the title compound as a pale yellow oil (125 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.70 (4H, m), 2.78-2.88 (4H, m), 2.84 (3H, s), 3.00 (2H, t, J = 8.5Hz), 3.08-3.24 (2H, m), 3.31-3.40 (2H, m), 3.48 (2H, t, J = 8.5Hz), 3.81 (3H, s), 6.34 (1H, d, J = 8Hz ), 6.82-6.88 (2H, m), 7.08-7.20 (2H, m), 7.67 (1H, s), 7.76 (1H, d, J = 8Hz).

Reference Example 52

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチルおよびヨウ化エチルを用いて、参考例５０と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.18(3H, t, J = 7.4Hz), 1.43(9H, s), 1.51-1.72(4H, m), 2.78-2.88(4H, m), 3.00(2H, t, J = 8.5Hz), 3.08-3.23(2H, m), 3.25(2H, q, J = 7.4Hz), 3.31-3.41(2H, m), 3.52(2H, t, J = 8.5Hz), 3.81(3H, s), 6.33(1H, d, J = 8Hz), 6.82-6.88(2H, m), 7.08-7.20(2H, m), 7.67(1H, s), 7.74(1H, d, J = 8Hz). Tert-Butyl 5- (1-ethyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate

Using tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 50 and ethyl iodide In the same manner as in Reference Example 50, the title compound was obtained as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.18 (3H, t, J = 7.4Hz), 1.43 (9H, s), 1.51-1.72 (4H, m), 2.78-2.88 (4H, m), 3.00 (2H , t, J = 8.5Hz), 3.08-3.23 (2H, m), 3.25 (2H, q, J = 7.4Hz), 3.31-3.41 (2H, m), 3.52 (2H, t, J = 8.5Hz) , 3.81 (3H, s), 6.33 (1H, d, J = 8Hz), 6.82-6.88 (2H, m), 7.08-7.20 (2H, m), 7.67 (1H, s), 7.74 (1H, d, J = 8Hz).

Reference Example 53

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチルおよび3-ブロモ-1-プロパノールを用いて、参考例５０と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43(9H, s), 1.51-1.70(4H, m), 1.75(1H, br.s), 1.85(2H, t, J = 6.7Hz), 2.78-2.88(4H, m), 3.01(2H, t, J = 8.5Hz), 3.08-3.24(2H, m), 3.30-3.40(2H, m), 3.32(2H, t, J = 6.7Hz), 3.54(2H, t, J = 8.5Hz), 3.76(2H, t, J = 7.6Hz), 3.82(3H, s), 6.39(1H, d, J = 8Hz), 6.82-6.88(2H, m), 7.08-7.20(2H, m), 7.67(1H, s), 7.73(1H, d, J = 8Hz). Tert-Butyl 5- [1- (3-hydroxypropyl) -2,3-dihydro-1H-indol-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate

5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl and 3-bromo-1 obtained in Reference Example 50 The title compound was obtained as a pale-yellow oil by performing the same operation as in Reference Example 50 using -propanol.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.70 (4H, m), 1.75 (1H, br.s), 1.85 (2H, t, J = 6.7Hz), 2.78-2.88 (4H, m), 3.01 (2H, t, J = 8.5Hz), 3.08-3.24 (2H, m), 3.30-3.40 (2H, m), 3.32 (2H, t, J = 6.7Hz), 3.54 ( 2H, t, J = 8.5Hz), 3.76 (2H, t, J = 7.6Hz), 3.82 (3H, s), 6.39 (1H, d, J = 8Hz), 6.82-6.88 (2H, m), 7.08 -7.20 (2H, m), 7.67 (1H, s), 7.73 (1H, d, J = 8Hz).

Reference Example 54

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチルおよびブロモ酢酸エチルを用いて、参考例５０と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.27(3H, t, J = 7Hz), 1.43(9H, s), 1.51-1.73(4H, m), 2.75-2.88(4H, m), 3.08(2H, t, J = 8.5Hz), 3.15-3.23(2H, m), 3.30-3.40(2H, m), 3.67(2H, t, J = 8.5Hz), 3.81(3H, s), 3.96(2H, s), 4.20(2H, q, J = 7Hz), 6.29(1H, d, J = 8Hz), 6.82-6.88(2H, m), 7.08-7.20(2H, m), 7.70(1H, s), 7.73(1H, d, J = 8Hz). [5- (5-[(tert-Butoxycarbonyl) [2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -2,3-dihydro-1H-indol-1-yl] ethyl acetate

Using tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate and ethyl bromoacetate obtained in Reference Example 50 In the same manner as in Reference Example 50, the title compound was obtained as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.27 (3H, t, J = 7Hz), 1.43 (9H, s), 1.51-1.73 (4H, m), 2.75-2.88 (4H, m), 3.08 (2H, t, J = 8.5Hz), 3.15-3.23 (2H, m), 3.30-3.40 (2H, m), 3.67 (2H, t, J = 8.5Hz), 3.81 (3H, s), 3.96 (2H, s ), 4.20 (2H, q, J = 7Hz), 6.29 (1H, d, J = 8Hz), 6.82-6.88 (2H, m), 7.08-7.20 (2H, m), 7.70 (1H, s), 7.73 (1H, d, J = 8Hz).

Reference Example 55

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(362mg) のテトラヒドロフラン(2ml) 溶液にイソシアン酸エチル(85mg) を加え、60℃で2時間攪拌した。溶媒を減圧下留去し、得られた残渣に水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；ヘキサン：酢酸エチル＝１：１)にて精製し、表題化合物を淡黄色油状物(254mg)として得た。
¹H NMR(400MHz, CD₃OD) δ 1.22(3H, t, J = 7Hz), 1.43(9H, s), 1.51-1.73(4H, m), 2.76-2.95(4H, m), 3.07-3.23(4H, m), 3.30-3.42(4H, m), 3.82(3H, s), 3.94(2H, t, J = 8Hz), 4.70(1H, br.s), 6.82-6.88(2H, m), 7.08-7.20(2H, m), 7.75(1H, s), 7.80(1H, d, J = 8.5Hz), 7.96(1H, d, J = 8.5Hz). 5- [1-[(Ethylamino) carbonyl] -2,3-dihydro-1H-indol-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Tetrahydrofuran of tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate (362 mg) obtained in Reference Example 50 2 ml) To the solution was added ethyl isocyanate (85 mg), and the mixture was stirred at 60 ° C. for 2 hours. The solvent was evaporated under reduced pressure, water was added to the resulting residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; hexane: ethyl acetate = 1: 1) to obtain the title compound as a pale yellow oil (254 mg).
¹ H NMR (400MHz, CD ₃ OD) δ 1.22 (3H, t, J = 7Hz), 1.43 (9H, s), 1.51-1.73 (4H, m), 2.76-2.95 (4H, m), 3.07-3.23 (4H, m), 3.30-3.42 (4H, m), 3.82 (3H, s), 3.94 (2H, t, J = 8Hz), 4.70 (1H, br.s), 6.82-6.88 (2H, m) , 7.08-7.20 (2H, m), 7.75 (1H, s), 7.80 (1H, d, J = 8.5Hz), 7.96 (1H, d, J = 8.5Hz).

Reference Example 56

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(3-フルオロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.44(9H, s), 1.52-1.76(4H, m), 2.81(2H, m), 2.91-2.95(2H, m), 3.14-3.23(2H, m), 3.38(2H, m), 4.69(2H, s), 6.87-7.01(4H, m), 7.20-7.25(1H, m), 7.59-7.61(2H, m), 9.40(1H, s). 2- (3-Fluorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert-butyl

Same as Reference Example 19 using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (3-fluorophenyl) ethylamine obtained in Reference Example 7 To give the title compound as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.52-1.76 (4H, m), 2.81 (2H, m), 2.91-2.95 (2H, m), 3.14-3.23 (2H, m) , 3.38 (2H, m), 4.69 (2H, s), 6.87-7.01 (4H, m), 7.20-7.25 (1H, m), 7.59-7.61 (2H, m), 9.40 (1H, s).

Reference Example 57

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(3-クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(200MHz, CDCl₃) δ 1.44(9H, s), 1.58(2H, m), 1.68-1.73(2H, m), 2.79(2H, m), 2.90-2.95(2H, m), 3.14-3.23(2H, m), 3.37(2H, m), 4.69(2H, s), 6.98-7.05(2H, m), 7.17-7.21(3H, m), 7.59-7.61(2H, m), 9.46(1H, s). 2- (3-Chlorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert-butyl

Similar to Reference Example 19 using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (3-chlorophenyl) ethylamine obtained in Reference Example 7. By performing the operation, the title compound was obtained as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.58 (2H, m), 1.68-1.73 (2H, m), 2.79 (2H, m), 2.90-2.95 (2H, m), 3.14 -3.23 (2H, m), 3.37 (2H, m), 4.69 (2H, s), 6.98-7.05 (2H, m), 7.17-7.21 (3H, m), 7.59-7.61 (2H, m), 9.46 (1H, s).

Reference Example 58

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび2-フェニルエチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.44(9H, s), 1.75-1.59(4H, m), 2.79-2.81(2H, m), 3.03-2.99(2H, m), 3.22-3.18(2H, m), 3.39-3.35(2H, m), 3.46(3H, s), 3.47(3H, s), 6.99(1H, d, J = 8.1Hz), 7.31-7.16(5H, m), 7.63(1H, d, J = 1.2Hz), 7.78(1H, d, J = 8.4Hz). 5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl (2-phenylethyl) carbamate tert-butyl

Same as Reference Example 19 using 5- (5-chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one and 2-phenylethylamine obtained in Reference Example 10 To give the title compound as a colorless oil.
¹ H NMR (300 MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.75-1.59 (4H, m), 2.79-2.81 (2H, m), 3.03-2.99 (2H, m), 3.22-3.18 (2H, m), 3.39-3.35 (2H, m), 3.46 (3H, s), 3.47 (3H, s), 6.99 (1H, d, J = 8.1Hz), 7.31-7.16 (5H, m), 7.63 (1H , d, J = 1.2Hz), 7.78 (1H, d, J = 8.4Hz).

Reference Example 59

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび2-(2-メトキシフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.43(9H, s), 1.73-1.64(4H, m), 2.84-2.80(2H, m), 3.03-2.99(2H, m), 3.23-3.21(2H, m), 3.37-3.33(2H, m), 3.47(6H, s), 3.82(3H, s), 6.90-6.82(2H, m), 6.98(1H, d, J = 8.4Hz), 7.21-7.17(2H, m), 7.63(1H, d, J = 1.5Hz), 7.79(1H, d, J = 8.1Hz) 5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Using 5- (5-chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 10, The title compound was obtained as a colorless oil by the same operation as in Reference Example 19.
¹ H NMR (300 MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.73-1.64 (4H, m), 2.84-2.80 (2H, m), 3.03-2.99 (2H, m), 3.23-3.21 (2H, m), 3.37-3.33 (2H, m), 3.47 (6H, s), 3.82 (3H, s), 6.90-6.82 (2H, m), 6.98 (1H, d, J = 8.4Hz), 7.21-7.17 (2H, m), 7.63 (1H, d, J = 1.5Hz), 7.79 (1H, d, J = 8.1Hz)

Reference Example 60

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(300MHz, CDCl₃) δ 1.74-1.41(13H, m), 3.01-2.94(4H, m), 3.24-3.15(2H, m), 3.44-3.39(2H, m), 3.46(3H, s), 3.47(3H, s), 6.99(1H, d, J = 8.1Hz), 7.17(3H, m), 7.35-7.32(1H, m), 7.63(1H, d, J = 1.5Hz), 7.79(1H, d, J = 8.1Hz). 2- (2-Chlorophenyl) ethyl [5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamate tert-butyl

Using 5- (5-chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 10, The title compound was obtained as a colorless oil by the same operation as in Example 19.
¹ H NMR (300 MHz, CDCl ₃ ) δ 1.74-1.41 (13H, m), 3.01-2.94 (4H, m), 3.24-3.15 (2H, m), 3.44-3.39 (2H, m), 3.46 (3H, s), 3.47 (3H, s), 6.99 (1H, d, J = 8.1Hz), 7.17 (3H, m), 7.35-7.32 (1H, m), 7.63 (1H, d, J = 1.5Hz), 7.79 (1H, d, J = 8.1Hz).

Reference Example 61

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチルおよびベンジルブロミドを用いて、参考例５１と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43(9H, s), 1.51-1.68(4H, m), 2.85(4H, br.s), 3.03(2H, t, J = 8.3Hz), 3.07-3.20(2H, m), 3.34(2H, br.s), 3.50(2H, t, J = 8.4Hz), 3.81(3H, s), 4.37(2H, s), 6.40(1H, d, J = 8.3Hz), 6.82-6.88(2H, m), 7.08-7.20(2H, m), 7.26-7.36(5H, m), 7.70(1H, s), 7.74(1H, d, J = 8.3Hz). Tert-Butyl 5- (1-benzyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate

Using tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate and benzyl bromide obtained in Reference Example 50 The title compound was obtained as a colorless oil by the same operations as in Reference Example 51.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.68 (4H, m), 2.85 (4H, br.s), 3.03 (2H, t, J = 8.3Hz), 3.07-3.20 (2H, m), 3.34 (2H, br.s), 3.50 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.37 (2H, s), 6.40 (1H, d, J = 8.3 Hz), 6.82-6.88 (2H, m), 7.08-7.20 (2H, m), 7.26-7.36 (5H, m), 7.70 (1H, s), 7.74 (1H, d, J = 8.3Hz).

Reference Example 62

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチルおよびベンゾイルクロリドを用いて、参考例５５と同様の操作を行うことにより、表題化合物を無色油状物として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43(9H, s), 1.51-1.70(4H, m), 2.82(2H, br.s), 2.93(2H, br.s), 3.15(2H, t, J = 8.5Hz), 3.21(2H, br.s), 3.35(2H, br.s), 3.82(3H, s), 4.13(2H, t, J = 8.4Hz), 6.82-6.88(2H, m), 7.09-7.20(2H, m), 7.44-7.57(6H, m), 7.75(1H, br.s), 7.83(1H, s). Tert-Butyl 5- (1-benzoyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate

Using tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 50 and benzoyl chloride The title compound was obtained as a colorless oil by operations similar to those of Reference Example 55.
¹ H NMR (400 MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.70 (4H, m), 2.82 (2H, br.s), 2.93 (2H, br.s), 3.15 (2H, t, J = 8.5Hz), 3.21 (2H, br.s), 3.35 (2H, br.s), 3.82 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.82-6.88 (2H, m ), 7.09-7.20 (2H, m), 7.44-7.57 (6H, m), 7.75 (1H, br.s), 7.83 (1H, s).

Reference Example 63

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチルおよびイソシアン酸フェニルを用いて、参考例５５と同様の操作を行うことにより、表題化合物を融点136-137℃の無色結晶として得た。
¹H NMR(400MHz, CDCl₃) δ 1.43(9H, s), 1.51-1.70(4H, m), 2.82(2H, br.s), 2.91(2H, t, J = 7.0Hz), 3.13-3.26(4H, m), 3.35(2H, br.s), 3.81(3H, s), 4.11(2H, t, J = 8.4Hz), 6.36(1H, s), 6.82-6.88(2H, m), 7.08-7.20(3H, m), 7.33(2H, t, J = 8.3Hz), 7.45(2H, d, J = 8.0Hz), 7.78(1H, s), 7.81(1H, d, J = 8.5Hz), 7.98(1H, d, J = 8.0Hz). Tert-Butyl 5- [1- (anilinocarbonyl) -2,3-dihydro-1H-indol-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate

Using tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 50 and phenyl isocyanate Then, the title compound was obtained as colorless crystals having a melting point of 136-137 ° C. by carrying out the same operation as in Reference Example 55.
¹ H NMR (400 MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.70 (4H, m), 2.82 (2H, br.s), 2.91 (2H, t, J = 7.0 Hz), 3.13-3.26 (4H, m), 3.35 (2H, br.s), 3.81 (3H, s), 4.11 (2H, t, J = 8.4Hz), 6.36 (1H, s), 6.82-6.88 (2H, m), 7.08-7.20 (3H, m), 7.33 (2H, t, J = 8.3Hz), 7.45 (2H, d, J = 8.0Hz), 7.78 (1H, s), 7.81 (1H, d, J = 8.5Hz ), 7.98 (1H, d, J = 8.0Hz).

Reference Example 64

アニソール(15.0g) および5-クロロバレリルクロリド(18.0ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物を融点67-68℃の無色結晶(27.3g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.80-1.95 (4H, m), 2.90-3.00 (2H, m), 3,55-3.60 (2H, m), 3.86 (3H, s), 6.90-7.00 (2H, m), 7.90-8.00 (2H, m).
元素分析 C₁₂H₁₅ClO₂として
計算値：C, 63.58; H, 6.67; N, 0.00.
実験値：C, 63.50; H, 6.67; N, 0.00. 5-chloro-1- (4-methoxyphenyl) -1-pentanone

The title compound was obtained as colorless crystals (27.3 g) with a melting point of 67-68 ° C. by the same procedure as in Reference Example 1 using anisole (15.0 g) and 5-chlorovaleryl chloride (18.0 ml). .
¹ H NMR (300MHz, CDCl ₃ ) δ 1.80-1.95 (4H, m), 2.90-3.00 (2H, m), 3,55-3.60 (2H, m), 3.86 (3H, s), 6.90-7.00 ( 2H, m), 7.90-8.00 (2H, m).
Elemental analysis Calculated as C ₁₂ H ₁₅ ClO ₂ : C, 63.58; H, 6.67; N, 0.00.
Experimental value: C, 63.50; H, 6.67; N, 0.00.

Reference Example 65

参考例６４で得た5-クロロ-1-(4-メトキシフェニル)-1-ペンタノン(15.0g) を、氷冷下、クロロスルホン酸(50ml) に少量ずつ加えた。混合物を室温で３０時間攪拌後、反応溶液を粉砕氷(500g) に滴下し、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより、表題化合物を融点69-70℃の無色結晶(7.63g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.80-2.00 (4H, m), 2.95-3.05 (2H, m), 3,55-3.65 (2H, m), 4.15 (3H, s), 7.22 (1H, d, J = 8.8Hz), 8.33 (1H, dd, J = 8.8, 2.2Hz), 8.53 (1H, d, J = 2.2Hz).
元素分析 C₁₂H₁₄Cl₂O₄Sとして
計算値：C, 44.32; H, 4.34; N, 0.00.
実験値：C, 43.77; H, 4.36; N, 0.00. 5- (5-Chloropentanoyl) -2-methoxybenzenesulfonyl chloride

5-Chloro-1- (4-methoxyphenyl) -1-pentanone (15.0 g) obtained in Reference Example 64 was added little by little to chlorosulfonic acid (50 ml) under ice cooling. After stirring the mixture at room temperature for 30 hours, the reaction solution was added dropwise to crushed ice (500 g), then extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as colorless crystals (7.63 g) having a melting point of 69-70 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.80-2.00 (4H, m), 2.95-3.05 (2H, m), 3,55-3.65 (2H, m), 4.15 (3H, s), 7.22 (1H, d, J = 8.8Hz), 8.33 (1H, dd, J = 8.8, 2.2Hz), 8.53 (1H, d, J = 2.2Hz).
Elemental analysis Calculated as C ₁₂ H ₁₄ Cl ₂ O ₄ S: C, 44.32; H, 4.34; N, 0.00.
Experimental value: C, 43.77; H, 4.36; N, 0.00.

Reference Example 66

参考例６５で得た塩化5-(5-クロロペンタノイル)-2-メトキシベンゼンスルホニル(3.00g) のテトラヒドロフラン(50ml) 溶液に、25%アンモニア水を氷冷下にて滴下した。室温で３０分攪拌後、溶媒を減圧下留去し、次いで酢酸エチルで抽出し、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより、表題化合物を融点135-136℃の無色結晶(2.54g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 3.06 (2H, t, J = 6.2Hz), 3.69 (2H, t, J = 6.2Hz), 4.00 (3H, s), 7.28 (2H, s), 7.33 (1H, d, J = 8.8Hz), 8.22 (1H, dd, J = 8.8, 2.2Hz), 8.30 (1H, d, J = 2.2Hz).
元素分析 C₁₂H₁₆ClNO₄Sとして
計算値：C, 47.14; H, 5.27; N, 4.58.
実験値：C, 47.06; H, 5.25; N, 4.49. 5- (5-Chloropentanoyl) -2-methoxybenzenesulfonamide

To a solution of 5- (5-chloropentanoyl) -2-methoxybenzenesulfonyl chloride (3.00 g) obtained in Reference Example 65 in tetrahydrofuran (50 ml), 25% aqueous ammonia was added dropwise under ice cooling. After stirring at room temperature for 30 minutes, the solvent was distilled off under reduced pressure, then extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as colorless crystals (2.54 g) having a melting point of 135-136 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 3.06 (2H, t, J = 6.2Hz), 3.69 (2H, t, J = 6.2Hz), 4.00 (3H, s ), 7.28 (2H, s), 7.33 (1H, d, J = 8.8Hz), 8.22 (1H, dd, J = 8.8, 2.2Hz), 8.30 (1H, d, J = 2.2Hz).
Elemental analysis Calculated as C ₁₂ H ₁₆ ClNO ₄ S: C, 47.14; H, 5.27; N, 4.58.
Experimental values: C, 47.06; H, 5.25; N, 4.49.

Reference Example 67

参考例６５で得た塩化5-(5-クロロペンタノイル)-2-メトキシベンゼンスルホニル(3.50g) およびイソプロピルアミン(1.90ml) を用いて、参考例６６と同様の操作を行うことにより、表題化合物を融点122-124℃の無色結晶(3.39g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.08 (6H, d, J = 6.6Hz), 1.80-2.00 (4H, m), 2.95-3.05 (2H, m), 3.35-3.65 (3H, m), 4.07 (3H, s), 4.30-5.00 (1H, br), 7.12 (1H, d, J = 8.8Hz), 8.21 (1H, dd, J = 8.8, 2.2Hz), 8.50 (1H, d, J = 2.2Hz).
元素分析 C₁₅H₂₂ClNO₄Sとして
計算値：C, 51.79; H, 6.37; N, 4.03.
実験値：C, 51.74; H, 6.37; N, 3.83. 5- (5-Chloropentanoyl) -N-isopropyl-2-methoxybenzenesulfonamide

By performing the same operation as in Reference Example 66 using 5- (5-chloropentanoyl) -2-methoxybenzenesulfonyl chloride (3.50 g) and isopropylamine (1.90 ml) obtained in Reference Example 65, the title was obtained. The compound was obtained as colorless crystals (3.39 g) with a melting point of 122-124 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.08 (6H, d, J = 6.6Hz), 1.80-2.00 (4H, m), 2.95-3.05 (2H, m), 3.35-3.65 (3H, m), 4.07 (3H, s), 4.30-5.00 (1H, br), 7.12 (1H, d, J = 8.8Hz), 8.21 (1H, dd, J = 8.8, 2.2Hz), 8.50 (1H, d, J = 2.2 Hz).
Elemental analysis Calculated as C ₁₅ H ₂₂ ClNO ₄ S: C, 51.79; H, 6.37; N, 4.03.
Experimental value: C, 51.74; H, 6.37; N, 3.83.

Reference Example 68

2,3-ジヒドロ-1-ベンゾフラン(24.5g) および5-クロロバレリルクロリド(34.8g) を用いて、参考例１と同様の操作を行うことにより、表題化合物を融点56-57℃の無色結晶(32.4g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.80-2.00 (4H, m), 2.90-3.00 (2H, m), 3.25 (2H, t, J = 8.7Hz), 3.55-3.65 (2H, m), 4.66 (2H, t, J = 8.7Hz), 6.79 (1H, d, J = 8.2Hz), 7.79 (1H, dd, J = 8.2, 2.1Hz), 7.84 (1H, d, J = 2.1Hz).
元素分析 C₁₃H₁₅ClO₂として
計算値：C, 65.41; H, 6.33; N, 0.00.
実験値：C, 65.18; H, 6.33; N, 0.00. 5-Chloro-1- (2,3-dihydro-1-benzofuran-5-yl) -1-pentanone

The title compound was purified in the same manner as in Reference Example 1 using 2,3-dihydro-1-benzofuran (24.5 g) and 5-chlorovaleryl chloride (34.8 g) to give a colorless compound having a melting point of 56-57 ° C. Obtained as crystals (32.4 g).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.80-2.00 (4H, m), 2.90-3.00 (2H, m), 3.25 (2H, t, J = 8.7Hz), 3.55-3.65 (2H, m), 4.66 (2H, t, J = 8.7Hz), 6.79 (1H, d, J = 8.2Hz), 7.79 (1H, dd, J = 8.2, 2.1Hz), 7.84 (1H, d, J = 2.1Hz).
Elemental analysis Calculated as C ₁₃ H ₁₅ ClO ₂ : C, 65.41; H, 6.33; N, 0.00.
Experimental value: C, 65.18; H, 6.33; N, 0.00.

Reference Example 69

参考例６８で得た5-クロロ-1-(2,3-ジヒドロ-1-ベンゾフラン-5-イル)-1-ペンタノン(10.0g) を用いて、参考例６５と同様の操作を行うことにより、表題化合物を融点72-73℃の無色結晶(4.93g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.80-2.00 (4H, m), 2.90-3.05 (2H, m), 3.41 (2H, t, J = 8.8Hz), 3.55-3.65 (2H, m), 5.01 (2H, t, J = 8.8Hz), 8.15-8.20 (1H, m), 8.25-8.30 (1H, m).
元素分析 C₁₃H₁₄Cl₂O₄Sとして
計算値：C, 46.30; H, 4.18; N, 0.00.
実験値：C, 46.13; H, 4.17; N, 0.00. 5- (5-Chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonyl chloride

By using the same procedure as in Reference Example 65, using 5-chloro-1- (2,3-dihydro-1-benzofuran-5-yl) -1-pentanone (10.0 g) obtained in Reference Example 68 The title compound was obtained as colorless crystals (4.93 g) with a melting point of 72-73 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.80-2.00 (4H, m), 2.90-3.05 (2H, m), 3.41 (2H, t, J = 8.8Hz), 3.55-3.65 (2H, m), 5.01 (2H, t, J = 8.8Hz), 8.15-8.20 (1H, m), 8.25-8.30 (1H, m).
Elemental analysis Calculated as C ₁₃ H ₁₄ Cl ₂ O ₄ S: C, 46.30; H, 4.18; N, 0.00.
Experimental value: C, 46.13; H, 4.17; N, 0.00.

Reference Example 70

参考例６９で得た塩化5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホニル(4.50g) を用いて、参考例６６と同様の操作を行うことにより、表題化合物を融点134-136℃の無色結晶(3.87g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.65-1.85 (4H, m), 3.02 (2H, t, J = 7.0Hz), 3.32 (2H, t, J = 8.8Hz), 3.68 (2H, t, J = 7.0Hz), 4.82 (2H, t, J = 8.8Hz), 7.38 (2H, s), 8.05-8.10 (2H, m).
元素分析 C₁₃H₁₆ClNO₄Sとして
計算値：C, 49.13; H, 5.07; N, 4.41.
実験値：C, 48.96; H, 4.99; N, 4.15. 5- (5-Chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide

By performing the same operation as in Reference Example 66 using 5- (5-chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonyl chloride (4.50 g) obtained in Reference Example 69, The title compound was obtained as colorless crystals (3.87 g) with a melting point of 134-136 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.65-1.85 (4H, m), 3.02 (2H, t, J = 7.0Hz), 3.32 (2H, t, J = 8.8Hz), 3.68 (2H, t , J = 7.0Hz), 4.82 (2H, t, J = 8.8Hz), 7.38 (2H, s), 8.05-8.10 (2H, m).
Elemental analysis Calculated as C ₁₃ H ₁₆ ClNO ₄ S: C, 49.13; H, 5.07; N, 4.41.
Experimental value: C, 48.96; H, 4.99; N, 4.15.

Reference Example 71

参考例６９で得た塩化5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホニル(4.50g) およびイソプロピルアミン(3.80ml) を用いて、参考例６６と同様の操作を行うことにより、表題化合物を融点103-104℃の無色結晶(6.76g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.11 (6H, d, J = 6.6Hz), 1.80-2.00 (4H, m), 2.90-3.05 (2H, m), 3.34 (2H, t, J = 8.8Hz), 3.40-3.65 (3H, m), 4.71 (1H, d, J = 7.0Hz), 4.87 (2H, t, J = 8.8Hz), 8.00-8.10 (1H, m), 8.20-8.25 (1H, m).
元素分析 C₁₆H₂₂NO₄SClとして
計算値：C, 53.40; H, 6.16; N, 3.89.
実験値：C, 53.32; H, 6.16; N, 3.84. 5- (5-Chloropentanoyl) -N-isopropyl-2,3-dihydro-1-benzofuran-7-sulfonamide

Similar to Reference Example 66 using 5- (5-chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonyl chloride (4.50 g) and isopropylamine (3.80 ml) obtained in Reference Example 69 The title compound was obtained as colorless crystals (6.76 g) having a melting point of 103-104 ° C.
_{^{1 H NMR (200MHz, CDCl 3}} ) δ 1.11 (6H, d, J = 6.6Hz), 1.80-2.00 (4H, m), 2.90-3.05 (2H, m), 3.34 (2H, t, J = 8.8Hz ), 3.40-3.65 (3H, m), 4.71 (1H, d, J = 7.0Hz), 4.87 (2H, t, J = 8.8Hz), 8.00-8.10 (1H, m), 8.20-8.25 (1H, m).
Elemental analysis Calculated as C ₁₆ H ₂₂ NO ₄ SCl: C, 53.40; H, 6.16; N, 3.89.
Experimental value: C, 53.32; H, 6.16; N, 3.84.

Reference Example 72

2,2-ジメチルクロマン(19.7g) および5-クロロバレリルクロリド(20.7g) を用いて、参考例１と同様の操作を行うことにより、表題化合物を融点50-51℃の無色結晶(22.0g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.36 (6H, s), 1.80-1.95 (6H, m), 2.82 (2H, t, J = 6.6Hz), 2.80-3.00 (2H, m), 3.55-3.65 (2H, m), 6.80 (1H, d, J = 9.0Hz), 7.70-7.80 (2H, m).
元素分析 C₁₆H₂₁ClO₂として
計算値：C, 68.44; H, 7.68; N, 0.00.
実験値：C, 68.31; H, 7.54; N, 0.00. 5-Chloro-1- (2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl) -1-pentanone

The title compound was purified in the same manner as in Reference Example 1 using 2,2-dimethylchroman (19.7 g) and 5-chlorovaleryl chloride (20.7 g) to give colorless crystals (22.0 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.36 (6H, s), 1.80-1.95 (6H, m), 2.82 (2H, t, J = 6.6Hz), 2.80-3.00 (2H, m), 3.55-3.65 (2H, m), 6.80 (1H, d, J = 9.0Hz), 7.70-7.80 (2H, m).
Elemental analysis Calculated as C ₁₆ H ₂₁ ClO ₂ : C, 68.44; H, 7.68; N, 0.00.
Experimental value: C, 68.31; H, 7.54; N, 0.00.

Reference Example 73

参考例７２で得た5-クロロ-1-(2,2-ジメチル-3,4-ジヒドロ-2H-クロメン-6-イル)-1-ペンタノン(5.00g) を用いて、参考例６５と同様の操作を行うことにより、表題化合物を無色油状物(1.30g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.50 (6H, s), 1.75-2.10 (6H, m), 2.85-3.05 (4H, m), 3.55-3.65 (2H, m), 8.60 (1H, s), 8.33 (1H, s). 6- (5-Chloropentanoyl) -2,2-dimethyl-8-chromansulfonyl chloride

Similar to Reference Example 65 using 5-chloro-1- (2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl) -1-pentanone (5.00 g) obtained in Reference Example 72 To give the title compound as a colorless oil (1.30 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.50 (6H, s), 1.75-2.10 (6H, m), 2.85-3.05 (4H, m), 3.55-3.65 (2H, m), 8.60 (1H, s) , 8.33 (1H, s).

Reference Example 74

参考例７３で得た塩化6-(5-クロロペンタノイル)-2,2-ジメチル-8-クロマンスルホニル(1.30g) を用いて、参考例６６と同様の操作を行うことにより、表題化合物を融点148-149℃の無色結晶(630mg)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.48 (6H, s), 1.80-1.90 (4H, m), 1.95 (2H, t, J = 6.9Hz), 2.91 (2H, t, J = 6.9Hz), 2.95-3.00 (2H, m), 3.55-3.60 (2H, m), 5.03 (2H, s), 7.95-8.00 (1H, m), 8.25-8.30 (1H, m). 6- (5-Chloropentanoyl) -2,2-dimethyl-8-chromansulfonamide

The title compound was obtained by the same procedure as in Reference Example 66 using 6- (5-chloropentanoyl) -2,2-dimethyl-8-chromansulfonyl (1.30 g) chloride obtained in Reference Example 73. Obtained as colorless crystals (630 mg) of melting point 148-149 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.48 (6H, s), 1.80-1.90 (4H, m), 1.95 (2H, t, J = 6.9Hz), 2.91 (2H, t, J = 6.9Hz), 2.95-3.00 (2H, m), 3.55-3.60 (2H, m), 5.03 (2H, s), 7.95-8.00 (1H, m), 8.25-8.30 (1H, m).

Reference Example 75

2,3-ジヒドロ-1,4-ベンゾジオキシン(10.0g) および5-クロロバレリルクロリド(10.4ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物を融点52-53℃の無色結晶(15.1g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.80-1.95 (4H, m), 2.90-3.00 (2H, m), 3.55-3.60 (2H, m), 4.25-4.35 (4H, s), 6.85-6.95 (1H, m), 7.45-7.50 (2H, m).
元素分析 C₁₃H₁₅ClO₃として
計算値：C, 61.30; H, 5.94; N, 0.00.
実験値：C, 61.26; H, 5.83; N, 0.00. 5-Chloro-1- (2,3-dihydro-1,4-benzodioxin-6-yl) -1-pentanone

By performing the same operation as in Reference Example 1 using 2,3-dihydro-1,4-benzodioxin (10.0 g) and 5-chlorovaleryl chloride (10.4 ml), the title compound was melted at a melting point of 52-53. Obtained as colorless crystals (15.1 g) at ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.80-1.95 (4H, m), 2.90-3.00 (2H, m), 3.55-3.60 (2H, m), 4.25-4.35 (4H, s), 6.85-6.95 ( 1H, m), 7.45-7.50 (2H, m).
Elemental analysis Calculated as C ₁₃ H ₁₅ ClO ₃ : C, 61.30; H, 5.94; N, 0.00.
Experimental value: C, 61.26; H, 5.83; N, 0.00.

Reference Example 76

参考例７５で得た5-クロロ-1-(2,3-ジヒドロ-1,4-ベンゾジオキシン-6-イル)-1-ペンタノン(9.00g) を用いて、参考例６５および６６と同様の操作を順次行うことにより、表題化合物を融点141-142℃の無色結晶(3.88g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.80-1.95 (4H, m), 2.94 (2H, t, J = 6.6Hz), 3.58 (2H, t, J = 6.0Hz), 4.30-4.45 (2H, m), 4.50-4.60 (2H, m), 5.20 (2H, s), 7.67 (1H, d, J = 1.8Hz), 7.99 (1H, d, J = 1.8Hz).
元素分析 C₁₃H₁₆ClNO₅Sとして
計算値：C, 46.78; H, 4.83; N, 4.20.
実験値：C, 46.63; H, 4.83; N, 4.10. 7- (5-Chloropentanoyl) -2,3-dihydro-1,4-benzodioxin-5-sulfonamide

Using 5-chloro-1- (2,3-dihydro-1,4-benzodioxin-6-yl) -1-pentanone (9.00 g) obtained in Reference Example 75, the same as in Reference Examples 65 and 66 By sequentially performing the operation, the title compound was obtained as colorless crystals (3.88 g) having a melting point of 141-142 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.80-1.95 (4H, m), 2.94 (2H, t, J = 6.6Hz), 3.58 (2H, t, J = 6.0Hz), 4.30-4.45 (2H, m ), 4.50-4.60 (2H, m), 5.20 (2H, s), 7.67 (1H, d, J = 1.8Hz), 7.99 (1H, d, J = 1.8Hz).
Elemental analysis Calculated as C ₁₃ H ₁₆ ClNO ₅ S: C, 46.78; H, 4.83; N, 4.20.
Experimental values: C, 46.63; H, 4.83; N, 4.10.

Reference Example 77

trans-4-[(アセチルアミノ)メチル]シクロヘキサンカルボン酸(12.1g) を塩化チオニル(25ml) に水冷下、少量ずつ加えた。室温で３０分攪拌後、減圧下、塩化チオニルを留去し、trans-塩化4-[(アセチルアミノ)メチル]シクロヘキサンカルボニルの粗結晶を得た。次いで該粗結晶および1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(12.1g)のジクロロメタン(30ml) 溶液に、水冷下、塩化アルミニウム(24.0g) を少量ずつ加えた。室温で１２時間攪拌後、反応溶液を氷(300g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより、表題化合物を融点178-180℃の無色結晶(12.9g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.05-1.20 (2H, m), 1.45-1.60 (3H, m), 1.70-2.05 (4H, m), 2.01 (3H, s), 2.72 (2H, t, J = 7.8Hz), 3.03 (2H, t, J = 7.8Hz), 3.10-3.30 (5H, m), 4.13 (2H, t, J = 8.4Hz), 5.55-5.70 (1H, m), 7.64 (1H, s), 7.69 (1H, s). trans-N-({4-[(4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) carbonyl] cyclohexyl} methyl) acetamide

trans-4-[(Acetylamino) methyl] cyclohexanecarboxylic acid (12.1 g) was added in small portions to thionyl chloride (25 ml) under water cooling. After stirring at room temperature for 30 minutes, thionyl chloride was distilled off under reduced pressure to obtain crude crystals of trans-4-[(acetylamino) methyl] cyclohexanecarbonyl trans-. The crude crystals and 1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (12.1 g) in dichloromethane (30 ml) were then added with aluminum chloride (30 ml) under water cooling. 24.0 g) was added in small portions. After stirring at room temperature for 12 hours, the reaction solution was poured into ice (300 g), extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as colorless crystals (12.9 g) having a melting point of 178-180 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.05-1.20 (2H, m), 1.45-1.60 (3H, m), 1.70-2.05 (4H, m), 2.01 (3H, s), 2.72 (2H, t, J = 7.8Hz), 3.03 (2H, t, J = 7.8Hz), 3.10-3.30 (5H, m), 4.13 (2H, t, J = 8.4Hz), 5.55-5.70 (1H, m), 7.64 ( 1H, s), 7.69 (1H, s).

Reference Example 78

参考例７７で得たtrans-N-({4-[(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)カルボニル]シクロヘキシル}メチル)アセトアミド(12.0g) に濃塩酸(100ml) を加え、140℃で１２時間攪拌した。塩酸を減圧下留去することにより白色粉末を得た。さらに水−イソプロピルエーテルからの再結晶により、表題化合物を融点255-257℃の無色結晶(9.40g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.00-1.95 (10H, m), 2.50-2.75 (3H, m), 2.98 (2H, t, J = 7.8Hz), 3.18 (2H, t, J = 8.8Hz), 3.20-3.40 (1H, m), 3.99 (2H, t, J = 8.8Hz), 7.72 (1H, s), 7.73 (1H, s), 7.90-8.20 (3H, br). trans-8-{[4- (Aminomethyl) cyclohexyl] carbonyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

Trans-N-({4-[(4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) carbonyl] obtained in Reference Example 77 Concentrated hydrochloric acid (100 ml) was added to (cyclohexyl} methyl) acetamide (12.0 g), and the mixture was stirred at 140 ° C. for 12 hours. Hydrochloric acid was distilled off under reduced pressure to obtain a white powder. Further, recrystallization from water-isopropyl ether gave the title compound as colorless crystals (9.40 g) having a melting point of 255-257 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.00-1.95 (10H, m), 2.50-2.75 (3H, m), 2.98 (2H, t, J = 7.8Hz), 3.18 (2H, t, J = 8.8Hz), 3.20-3.40 (1H, m), 3.99 (2H, t, J = 8.8Hz), 7.72 (1H, s), 7.73 (1H, s), 7.90-8.20 (3H, br).

Reference Example 79

参考例1で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(4-メトキシフェニル)エチルアミン(1.03g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.23g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.45 (9H, s), 1.50-1.95 (4H, m), 2.65-2.80 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.85-3.00 (2H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.40 (4H, m), 3.21 (2H, t, J = 8.4Hz), 3.78 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.82 (2H, d, J = 8.4Hz), 7.00-7.15 (2H, m), 7.66 (1H, s), 7.70 (1H, s). 2- (4-Methoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The same operation as in Reference Example 19 was performed using (4-methoxyphenyl) ethylamine (1.03 g) to give the title compound (1.23 g) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.45 (9H, s), 1.50-1.95 (4H, m), 2.65-2.80 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.85-3.00 (2H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.40 (4H, m), 3.21 (2H, t, J = 8.4Hz), 3.78 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.82 (2H, d, J = 8.4Hz), 7.00-7.15 (2H, m), 7.66 (1H, s), 7.70 (1H, s).

Reference Example 80

参考例1で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(4-クロロフェニル)エチルアミン(1.06g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(941mg) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.43 (9H, s), 1.50-1.95 (4H, m), 2.65-2.85 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.85-3.00 (2H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.45 (4H, m), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.00-7.30 (4H, m), 7.66 (1H, s), 7.70 (1H, s). 2- (4-Chlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The title compound (941 mg) was obtained as a colorless oil by the same operation as in Reference Example 19 using (4-chlorophenyl) ethylamine (1.06 g).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.50-1.95 (4H, m), 2.65-2.85 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.85-3.00 (2H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.45 (4H, m), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz) , 7.00-7.30 (4H, m), 7.66 (1H, s), 7.70 (1H, s).

Reference Example 81

参考例1で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(3-クロロフェニル)エチルアミン(1.06g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.19g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.43 (9H, s), 1.50-1.90 (4H, m), 2.65-2.85 (2H, m), 2.70 (2H, t, J = 7.8Hz), 2.85-3.00 (2H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.25 (2H, m), 3.21 (2H, t, J = 8.4Hz), 3.36 (2H, t, J = 7.5Hz), 4.12 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.65 (1H, s), 7.70 (1H, s). 2- (3-Chlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The same operation as in Reference Example 19 was carried out using (3-chlorophenyl) ethylamine (1.06 g) to give the title compound (1.19 g) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.50-1.90 (4H, m), 2.65-2.85 (2H, m), 2.70 (2H, t, J = 7.8Hz), 2.85-3.00 (2H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.25 (2H, m), 3.21 (2H, t, J = 8.4Hz), 3.36 (2H, t, J = 7.5Hz) , 4.12 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.65 (1H, s), 7.70 (1H, s).

Reference Example 82

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g)、2-(2-ヒドロキシフェニル)エチルアミン・臭化水素酸塩(1.49g) およびジイソプロピルエチルアミン(1.16ml) のジメチルホルムアミド(1ml) 混合物を120℃で１時間攪拌した。室温まで冷却後、反応溶液にメタノール(10ml) およびトリエチルアミン(1.43ml) を加え、次いで二炭酸ジ-t-ブチル(2.24g) のメタノール(5ml) 溶液を滴下し、室温で１２時間攪拌した。溶媒を減圧下留去し、得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；ヘキサン：酢酸エチル＝２：１)にて精製し、溶媒を留去することにより、表題化合物を融点154-155℃の無色結晶(687mg)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.48 (9H, s), 1.55-1.85 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.83 (2H, t, J = 7.5Hz), 2.94 (2H, t, J = 7.5Hz), 3.00 (2H, t, J = 7.8Hz), 3.15-3.35 (6H, m), 4.12 (2H, t, J = 8.4Hz), 6.70-7.15 (4H, m), 7.66 (1H, s), 7.70 (1H, s), 7.40-7.65 (1H, br).
元素分析 C₂₉H₃₆N₂O₅・0.2H₂Oとして
計算値：C, 70.19; H, 7.39; N, 5.65.
実験値：C, 70.34; H, 7.35; N, 5.66. 2- (2-Hydroxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1, 2- A mixture of (2-hydroxyphenyl) ethylamine hydrobromide (1.49 g) and diisopropylethylamine (1.16 ml) in dimethylformamide (1 ml) was stirred at 120 ° C. for 1 hour. After cooling to room temperature, methanol (10 ml) and triethylamine (1.43 ml) were added to the reaction solution, and then a solution of di-t-butyl dicarbonate (2.24 g) in methanol (5 ml) was added dropwise and stirred at room temperature for 12 hours. The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel chromatography (developing solvent; hexane: ethyl acetate = 2: 1), and the solvent was distilled off to obtain the title compound having a melting point of 154-155 ° C. As colorless crystals (687 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.48 (9H, s), 1.55-1.85 (4H, m), 2.71 (2H, t, J = 7.8Hz), 2.83 (2H, t, J = 7.5Hz), 2.94 (2H, t, J = 7.5Hz), 3.00 (2H, t, J = 7.8Hz), 3.15-3.35 (6H, m), 4.12 (2H, t, J = 8.4Hz), 6.70-7.15 (4H m), 7.66 (1H, s), 7.70 (1H, s), 7.40-7.65 (1H, br).
Elemental analysis Calculated as C ₂₉ H ₃₆ N ₂ O ₅ · 0.2H ₂ O: C, 70.19; H, 7.39; N, 5.65.
Experimental values: C, 70.34; H, 7.35; N, 5.66.

Reference Example 83

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(2,6-ジクロロフェニル)エチルアミン(650mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.08g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.42 (9H, s), 1.50-1.80 (4H, m), 1.80-1.95 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.85-3.65 (10H, m), 4.13 (2H, t, J = 8.4Hz), 7.10 (1H, t, J = 7.8Hz), 7.25-7.30 (2H, m), 7.68 (1H, s), 7.72 (1H, s). 2- (2,6-Dichlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) Pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The title compound (1.08 g) was obtained as a colorless oil by the same operation as in Reference Example 19 using (2,6-dichlorophenyl) ethylamine (650 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.50-1.80 (4H, m), 1.80-1.95 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.85-3.65 (10H, m), 4.13 (2H, t, J = 8.4Hz), 7.10 (1H, t, J = 7.8Hz), 7.25-7.30 (2H, m), 7.68 (1H, s), 7.72 (1H, s).

Reference Example 84

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(2,3-ジメトキシフェニル)エチルアミン(620mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.13g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.46 (9H, s), 1.50-1.90 (6H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.45 (10H, m), 3.84 (3H, s), 3.86 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.70-6.85 (2H, m), 6.98 (1H, t, J = 7.8Hz), 7.67 (1H, s), 7.72 (1H, s). 2- (2,3-Dimethoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl ) Pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The title compound (1.13 g) was obtained as a colorless oil by the same procedure as in Reference Example 19 using (2,3-dimethoxyphenyl) ethylamine (620 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.46 (9H, s), 1.50-1.90 (6H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.45 (10H, m), 3.84 (3H , s), 3.86 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.70-6.85 (2H, m), 6.98 (1H, t, J = 7.8Hz), 7.67 (1H, s) , 7.72 (1H, s).

Reference Example 85

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(2-チエニル)エチルアミン(435mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.44g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.38 (9H, s), 1.40-1.85 (6H, m), 2.63 (2H, t, J = 7.8Hz), 2.80-3.55 (10H, m), 4.05 (2H, t, J = 7.2Hz), 6.70-6.80 (1H, m), 6.80-6.90 (1H, m), 7.00-7.10 (1H, m), 7.61 (1H, s), 7.65 (1H, s). 5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl [2- (2-thienyl) ethyl] Tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2- The title compound (1.44 g) was obtained as a colorless oil by the same procedure as in Reference Example 19 using (2-thienyl) ethylamine (435 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.38 (9H, s), 1.40-1.85 (6H, m), 2.63 (2H, t, J = 7.8Hz), 2.80-3.55 (10H, m), 4.05 (2H , t, J = 7.2Hz), 6.70-6.80 (1H, m), 6.80-6.90 (1H, m), 7.00-7.10 (1H, m), 7.61 (1H, s), 7.65 (1H, s).

Reference Example 86

参考例７５で得た5-クロロ-1-(2,3-ジヒドロ-1,4-ベンゾジオキシン-6-イル)-1-ペンタノン(1.00g) および2-(2-メトキシフェニル)エチルアミン(594mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.84g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.43 (9H, s), 1.50-2.00 (4H, m), 2.75-3.60 (12H, m), 3.82 (3H, s), 6.80-7.25 (5H, m), 7.60-7.65 (1H, m), 7.79 (1H, dd, J = 8.2, 1.5Hz). Tert-Butyl 5- (2,3-dihydro-1,4-benzodioxin-6-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate

5-chloro-1- (2,3-dihydro-1,4-benzodioxin-6-yl) -1-pentanone (1.00 g) and 2- (2-methoxyphenyl) ethylamine (594 mg) obtained in Reference Example 75 ) To give the title compound (1.84 g) as a colorless oil by the same procedure as in Reference Example 19.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.50-2.00 (4H, m), 2.75-3.60 (12H, m), 3.82 (3H, s), 6.80-7.25 (5H, m) , 7.60-7.65 (1H, m), 7.79 (1H, dd, J = 8.2, 1.5Hz).

Reference Example 87

参考例６６で得た5-(5-クロロペンタノイル)-2-メトキシベンゼンスルホンアミド(900mg) および2-フェニルエチルアミン(713mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点121-122℃の無色結晶(1.07g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.30-1.75 (13H, m), 2.75-2.85 (2H, m), 2.90-3.00 (2H, m), 3.05-3.25 (2H, m), 3.36 (2H, t, J = 7.8Hz), 4.08 (3H, s), 5.37 (2H, s), 7.10 (1H, d, J = 8.8Hz), 7.10-7.30 (5H, m), 8.16 (1H, dd, J = 8.8, 2.1Hz), 8.44 (1H, d, J = 2.1Hz).
元素分析 C₂₅H₃₄N₂O₆Sとして
計算値：C, 61.20; H, 6.99; N, 5.71.
実験値：C, 61.20; H, 7.02; N, 5.66. 5- [3- (Aminosulfonyl) -4-methoxyphenyl] -5-oxopentyl (2-phenylethyl) carbamate tert-butyl

Using the 5- (5-chloropentanoyl) -2-methoxybenzenesulfonamide (900 mg) and 2-phenylethylamine (713 mg) obtained in Reference Example 66, the same procedure as in Reference Example 19 was performed to give the title. The compound was obtained as colorless crystals (1.07 g) with a melting point of 121-122 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.30-1.75 (13H, m), 2.75-2.85 (2H, m), 2.90-3.00 (2H, m), 3.05-3.25 (2H, m), 3.36 (2H, t, J = 7.8Hz), 4.08 (3H, s), 5.37 (2H, s), 7.10 (1H, d, J = 8.8Hz), 7.10-7.30 (5H, m), 8.16 (1H, dd, J = 8.8, 2.1Hz), 8.44 (1H, d, J = 2.1Hz).
Elemental analysis Calculated as C ₂₅ H ₃₄ N ₂ O ₆ S: C, 61.20; H, 6.99; N, 5.71.
Experimental value: C, 61.20; H, 7.02; N, 5.66.

Reference Example 88

参考例６６で得た5-(5-クロロペンタノイル)-2-メトキシベンゼンスルホンアミド(800mg) および2-(2-メトキシフェニル)エチルアミン(792mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(740mg) を無色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.30-1.80 (13H, m), 2.80 (2H, t, J = 7.6Hz), 2.90-3.00 (2H, m), 3.05-3.25 (2H, m), 3.33 (2H, t, J = 7.6Hz), 3.81 (3H, s), 4.07 (3H, s), 5.66 (2H, s), 6.80-6.95 (2H, m), 7.00-7.25 (3H, m), 8.10-8.20 (1H, m), 8.40-8.45 (1H, m). 5- [3- (aminosulfonyl) -4-methoxyphenyl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamic acid tert-butyl

Using 5- (5-chloropentanoyl) -2-methoxybenzenesulfonamide (800 mg) and 2- (2-methoxyphenyl) ethylamine (792 mg) obtained in Reference Example 66, the same procedure as in Reference Example 19 was performed. This gave the title compound (740 mg) as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.30-1.80 (13H, m), 2.80 (2H, t, J = 7.6Hz), 2.90-3.00 (2H, m), 3.05-3.25 (2H, m), 3.33 (2H, t, J = 7.6Hz), 3.81 (3H, s), 4.07 (3H, s), 5.66 (2H, s), 6.80-6.95 (2H, m), 7.00-7.25 (3H, m), 8.10-8.20 (1H, m), 8.40-8.45 (1H, m).

Reference Example 89

参考例６６で得た5-(5-クロロペンタノイル)-2-メトキシベンゼンスルホンアミド(900mg) および2-(2-クロロフェニル)エチルアミン(915mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点113-114℃の無色結晶(1.07g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.30-1.80 (13H, m), 2.90-3.00 (4H, m), 3.05-3.25 (2H, m), 3.38 (2H, t, J = 7.6Hz), 4.09 (3H, s), 5.43 (2H, s), 7.05-7.40 (5H, m), 8.16 (1H, dd, J = 8.7, 2.1Hz), 8.43 (1H, d, J = 2.1Hz).
元素分析 C₂₅H₃₃ClN₂O₆Sとして
計算値：C, 57.19; H, 6.33; N, 5.34.
実験値：C, 57.07; H, 6.34; N, 5.22. 5- [3- (aminosulfonyl) -4-methoxyphenyl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamic acid tert-butyl

Using 5- (5-chloropentanoyl) -2-methoxybenzenesulfonamide (900 mg) and 2- (2-chlorophenyl) ethylamine (915 mg) obtained in Reference Example 66, the same operation as in Reference Example 19 is performed. This gave the title compound as colorless crystals (1.07 g) with a melting point of 113-114 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.30-1.80 (13H, m), 2.90-3.00 (4H, m), 3.05-3.25 (2H, m), 3.38 (2H, t, J = 7.6Hz), 4.09 (3H, s), 5.43 (2H, s), 7.05-7.40 (5H, m), 8.16 (1H, dd, J = 8.7, 2.1Hz), 8.43 (1H, d, J = 2.1Hz).
Elemental analysis Calculated as C ₂₅ H ₃₃ ClN ₂ O ₆ S: C, 57.19; H, 6.33; N, 5.34.
Experimental values: C, 57.07; H, 6.34; N, 5.22.

Reference Example 90

参考例６７で得た5-(5-クロロペンタノイル)-N-イソプロピル-2-メトキシベンゼンスルホンアミド(800mg) および2-(2-メトキシフェニル)エチルアミン(696mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.36g) を無色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.07 (6H, d, J = 6.6Hz), 1.40-1.80 (13H, m), 2.80-3.50 (9H, m), 3.83 (3H, s), 4.07 (3H, s), 5.21 (1H, d, J = 7.2Hz), 6.80-6.95 (2H, m), 7.05-7.25(3H, m), 8.20 (1H, dd, J = 8.8, 2.2Hz), 8.51 (1H, d, J = 2.2Hz). 5- {3-[(Isopropylamino) sulfonyl] -4-methoxyphenyl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Using 5- (5-chloropentanoyl) -N-isopropyl-2-methoxybenzenesulfonamide (800 mg) and 2- (2-methoxyphenyl) ethylamine (696 mg) obtained in Reference Example 67, Reference Example 19 and The same operation was performed to obtain the title compound (1.36 g) as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.07 (6H, d, J = 6.6Hz), 1.40-1.80 (13H, m), 2.80-3.50 (9H, m), 3.83 (3H, s), 4.07 (3H , s), 5.21 (1H, d, J = 7.2Hz), 6.80-6.95 (2H, m), 7.05-7.25 (3H, m), 8.20 (1H, dd, J = 8.8, 2.2Hz), 8.51 ( (1H, d, J = 2.2Hz).

Reference Example 91

参考例６７で得た5-(5-クロロペンタノイル)-N-イソプロピル-2-メトキシベンゼンスルホンアミド(800mg) および2-(2-クロロフェニル)エチルアミン(716mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.28g) を無色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.07 (6H, d, J = 6.6Hz), 1.35-1.80 (13H, m), 2.85-3.50 (9H, m), 4.07 (3H, s), 4.87 (1H, d, J = 6.8Hz), 7.05-7.40 (5H, m), 8.20 (1H, dd, J = 8.8, 2.2Hz), 8.50 (1H, d, J = 2.2Hz). 2- (2-Chlorophenyl) ethyl (5- {3-[(isopropylamino) sulfonyl] -4-methoxyphenyl} -5-oxopentyl) carbamate tert-butyl

Similar to Reference Example 19 using 5- (5-chloropentanoyl) -N-isopropyl-2-methoxybenzenesulfonamide (800 mg) and 2- (2-chlorophenyl) ethylamine (716 mg) obtained in Reference Example 67 To give the title compound (1.28 g) as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.07 (6H, d, J = 6.6Hz), 1.35-1.80 (13H, m), 2.85-3.50 (9H, m), 4.07 (3H, s), 4.87 (1H , d, J = 6.8Hz), 7.05-7.40 (5H, m), 8.20 (1H, dd, J = 8.8, 2.2Hz), 8.50 (1H, d, J = 2.2Hz).

Reference Example 92

参考例７０で得た5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(800mg) および2-(2-メトキシフェニル)エチルアミン(762mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(990mg) を無色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.20-1.80 (13H, m), 2.75-3.00 (5H, m), 3.05-3.40 (5H, m), 3.82 (3H, s), 4.87 (2H, t, J = 8.6Hz), 5.50 (2H, s), 6.80-6.90 (2H, m), 7.00-7.25 (2H, m), 7.99 (1H, s), 8.17 (1H, s). 5- [7- (Aminosulfonyl) -2,3-dihydro-1-benzofuran-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Using 5- (5-chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide (800 mg) and 2- (2-methoxyphenyl) ethylamine (762 mg) obtained in Reference Example 70, The title compound (990 mg) was obtained as a colorless oil by an operation similar to that of Reference Example 19.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-1.80 (13H, m), 2.75-3.00 (5H, m), 3.05-3.40 (5H, m), 3.82 (3H, s), 4.87 (2H, t, J = 8.6Hz), 5.50 (2H, s), 6.80-6.90 (2H, m), 7.00-7.25 (2H, m), 7.99 (1H, s), 8.17 (1H, s).

Reference Example 93

参考例７０で得た5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(800mg) および2-(2-クロロフェニル)エチルアミン(784mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点114-115℃の無色結晶(1.04g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.25-1.80 (13H, m), 2.80-3.45 (10H, m), 4.90 (2H, t, J = 8.8Hz), 5.29 (2H, s), 7.10-7.40 (4H, m), 8.02 (1H, s), 8.20 (1H, s).
元素分析 C₂₆H₃₃ClN₂O₆Sとして
計算値：C, 58.14; H, 6.19; N, 5.22.
実験値：C, 57.93; H, 6.22; N, 5.12. 5- [7- (Aminosulfonyl) -2,3-dihydro-1-benzofuran-5-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate tert-butyl

Using 5- (5-chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide (800 mg) and 2- (2-chlorophenyl) ethylamine (784 mg) obtained in Reference Example 70, The same operation as in Example 19 was performed to give the title compound as colorless crystals (1.04 g) having a melting point of 114-115 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.25-1.80 (13H, m), 2.80-3.45 (10H, m), 4.90 (2H, t, J = 8.8Hz), 5.29 (2H, s), 7.10-7.40 (4H, m), 8.02 (1H, s), 8.20 (1H, s).
Elemental analysis Calculated as C ₂₆ H ₃₃ ClN ₂ O ₆ S: C, 58.14; H, 6.19; N, 5.22.
Experimental value: C, 57.93; H, 6.22; N, 5.12.

Reference Example 94

参考例７１で得た5-(5-クロロペンタノイル)-N-イソプロピル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(1.00g) および2-(2-メトキシフェニル)エチルアミン(841mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.00g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.09 (6H, d, J = 6.3Hz), 1.35-1.75 (13H, m), 2.75-3.50 (11H, m), 3.82 (3H, s), 4.75-4.90 (3H, m), 6.80-6.90 (2H, m), 7.05-7.20 (2H, m), 8.03 (1H, s), 8.23 (1H, s). 5- {7-[(Isopropylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

5- (5-Chloropentanoyl) -N-isopropyl-2,3-dihydro-1-benzofuran-7-sulfonamide (1.00 g) and 2- (2-methoxyphenyl) ethylamine (841 mg) obtained in Reference Example 71 ) To give the title compound (1.00 g) as a colorless oil by the same operation as in Reference Example 19.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.09 (6H, d, J = 6.3Hz), 1.35-1.75 (13H, m), 2.75-3.50 (11H, m), 3.82 (3H, s), 4.75-4.90 (3H, m), 6.80-6.90 (2H, m), 7.05-7.20 (2H, m), 8.03 (1H, s), 8.23 (1H, s).

Reference Example 95

参考例７１で得た5-(5-クロロペンタノイル)-N-イソプロピル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(2.00g) および2-(2-クロロフェニル)エチルアミン(1.73g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(2.10g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.10 (6H, d, J = 6.6Hz), 1.30-2.00 (13H, m), 2.80-3.50 (11H, m), 4.75-4.90 (3H, m), 7.10-7.40 (4H, m), 8.04 (1H, s), 8.23 (1H, s). 2- (2-Chlorophenyl) ethyl (5- {7-[(isopropylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl) carbamate tert-butyl

5- (5-Chloropentanoyl) -N-isopropyl-2,3-dihydro-1-benzofuran-7-sulfonamide (2.00 g) and 2- (2-chlorophenyl) ethylamine (1.73 g) obtained in Reference Example 71 ) To give the title compound (2.10 g) as a colorless oil by the same operation as in Reference Example 19.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.10 (6H, d, J = 6.6Hz), 1.30-2.00 (13H, m), 2.80-3.50 (11H, m), 4.75-4.90 (3H, m), 7.10 -7.40 (4H, m), 8.04 (1H, s), 8.23 (1H, s).

Reference Example 96

参考例７４で得た6-(5-クロロペンタノイル)-2,2-ジメチル-8-クロマンスルホンアミド(600mg) および2-(2-クロロフェニル)エチルアミン(548mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(715mg) を無色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.30-1.90 (13H, m), 1.47 (6H, s), 1.93 (2H, t, J = 6.6Hz), 2.80-3.30 (8H, m), 3.39 (2H, t, J = 6.6Hz), 5.26 (2H, s), 7.10-7.40 (4H, m), 7.92 (1H, s), 8.26 (1H, s). 5- [8- (Aminosulfonyl) -2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate tert-butyl

Using 6- (5-chloropentanoyl) -2,2-dimethyl-8-chromansulfonamide (600 mg) and 2- (2-chlorophenyl) ethylamine (548 mg) obtained in Reference Example 74, Reference Example 19 and The same operation was carried out to obtain the title compound (715 mg) as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.30-1.90 (13H, m), 1.47 (6H, s), 1.93 (2H, t, J = 6.6Hz), 2.80-3.30 (8H, m), 3.39 (2H , t, J = 6.6Hz), 5.26 (2H, s), 7.10-7.40 (4H, m), 7.92 (1H, s), 8.26 (1H, s).

Reference Example 97

参考例７６で得た7-(5-クロロペンタノイル)-2,3-ジヒドロ-1,4-ベンゾジオキシン-5-スルホンアミド(800mg) およびフェネチルアミン(582mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.05g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.35-1.80 (13H, m), 2.75-2.95 (4H, m), 3.05-3.25 (2H, m), 3.35 (2H, t, J = 7.5Hz), 4.30-4.40 (2H, m), 4.45-4.55 (2H, m), 5.40-5.50 (2H, m), 7.10-7.35 (5H, m), 7.64 (1H, s), 7.98 (1H, s). 5- [8- (Aminosulfonyl) -2,3-dihydro-1,4-benzodioxin-6-yl] -5-oxopentyl (2-phenylethyl) carbamate tert-butyl

Similar to Reference Example 19 using 7- (5-chloropentanoyl) -2,3-dihydro-1,4-benzodioxin-5-sulfonamide (800 mg) and phenethylamine (582 mg) obtained in Reference Example 76 To give the title compound (1.05 g) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.35-1.80 (13H, m), 2.75-2.95 (4H, m), 3.05-3.25 (2H, m), 3.35 (2H, t, J = 7.5Hz), 4.30 -4.40 (2H, m), 4.45-4.55 (2H, m), 5.40-5.50 (2H, m), 7.10-7.35 (5H, m), 7.64 (1H, s), 7.98 (1H, s).

Reference Example 98

参考例７６で得た7-(5-クロロペンタノイル)-2,3-ジヒドロ-1,4-ベンゾジオキシン-5-スルホンアミド(800mg) および2-(2-メトキシフェニル)エチルアミン(726mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(820mg) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.35-1.75 (13H, m), 2.80 (2H, t, J = 7.2Hz), 2.85-3.00 (2H, m), 3.05-3.25 (2H, m), 3.32 (2H, t, J = 7.2Hz), 3.82 (3H, s), 4.30-4.40 (2H, m), 4.45-4.55 (2H, m), 5.31 (2H, s), 6.80-7.20 (4H, m), 7.67 (1H, s), 8.01 (1H, s). 5- [8- (Aminosulfonyl) -2,3-dihydro-1,4-benzodioxin-6-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

7- (5-Chloropentanoyl) -2,3-dihydro-1,4-benzodioxin-5-sulfonamide (800 mg) and 2- (2-methoxyphenyl) ethylamine (726 mg) obtained in Reference Example 76 were used. And the title compound (820 mg) was obtained as a colorless oil by an operation similar to that of Reference Example 19.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.35-1.75 (13H, m), 2.80 (2H, t, J = 7.2Hz), 2.85-3.00 (2H, m), 3.05-3.25 (2H, m), 3.32 (2H, t, J = 7.2Hz), 3.82 (3H, s), 4.30-4.40 (2H, m), 4.45-4.55 (2H, m), 5.31 (2H, s), 6.80-7.20 (4H, m ), 7.67 (1H, s), 8.01 (1H, s).

Reference Example 99

参考例７６で得た7-(5-クロロペンタノイル)-2,3-ジヒドロ-1,4-ベンゾジオキシン-5-スルホンアミド(800mg) および2-(2-クロロフェニル)エチルアミン(746mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.08g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.30-1.80 (13H, m), 2.80-3.00 (4H, m), 3.05-3.25 (2H, m), 3.39 (2H, t, J = 7.2Hz), 4.30-4.40 (2H, m), 4.45-4.55 (2H, m), 5.25-5.50 (2H, m), 7.05-7.40 (4H, m), 7.66 (1H, s), 7.99 (1H, s). 5- [8- (Aminosulfonyl) -2,3-dihydro-1,4-benzodioxin-6-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate tert-butyl

Using 7- (5-chloropentanoyl) -2,3-dihydro-1,4-benzodioxin-5-sulfonamide (800 mg) and 2- (2-chlorophenyl) ethylamine (746 mg) obtained in Reference Example 76 In the same manner as in Reference Example 19, the title compound (1.08 g) was obtained as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.30-1.80 (13H, m), 2.80-3.00 (4H, m), 3.05-3.25 (2H, m), 3.39 (2H, t, J = 7.2Hz), 4.30 -4.40 (2H, m), 4.45-4.55 (2H, m), 5.25-5.50 (2H, m), 7.05-7.40 (4H, m), 7.66 (1H, s), 7.99 (1H, s).

Reference Example 100

参考例１３で得たN-[5-(5-クロロペンタノイル)-2-メトキシフェニル]メタンスルホンアミド(1.00g) およびフェネチルアミン(786mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.32g) を無色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.44(9H, s), 1.50-1.90(4H, m), 2.75-3.45(8H, m), 2.99(3H, s), 3.96(3H, s), 6.80-7.00(2H, m), 7.10-7.35(5H, m), 7.75-7.85(1H, m), 8.05-8.15(1H, m). 5- {4-Methoxy-3-[(methylsulfonyl) amino] phenyl} -5-oxopentyl (2-phenylethyl) carbamate tert-butyl

Perform the same operations as in Reference Example 19 using N- [5- (5-chloropentanoyl) -2-methoxyphenyl] methanesulfonamide (1.00 g) and phenethylamine (786 mg) obtained in Reference Example 13. Gave the title compound (1.32 g) as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.50-1.90 (4H, m), 2.75-3.45 (8H, m), 2.99 (3H, s), 3.96 (3H, s), 6.80 -7.00 (2H, m), 7.10-7.35 (5H, m), 7.75-7.85 (1H, m), 8.05-8.15 (1H, m).

Reference Example 101

参考例１３で得たN-[5-(5-クロロペンタノイル)-2-メトキシフェニル]メタンスルホンアミド(1.00g) および2-(2-メトキシフェニル)エチルアミン(1.42g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(550mg) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.43(9H, s), 1.50-1.80(4H, m), 2.75-3.40(4H, m), 2.99(3H, s), 3.83(3H, s), 3.05-3.45 (4H, m), 3.96(3H, s), 6.80-6.90(3H, m), 6.96(1H, d, J = 8.4Hz), 7.05-7.25(2H, m), 7.80(1H, dd, J = 8.4, 1.8Hz), 8.10(1H, d, J = 1.8Hz). 5- {4-Methoxy-3-[(methylsulfonyl) amino] phenyl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Using N- [5- (5-chloropentanoyl) -2-methoxyphenyl] methanesulfonamide (1.00 g) and 2- (2-methoxyphenyl) ethylamine (1.42 g) obtained in Reference Example 13, The same operation as in Example 19 was carried out to give the title compound (550 mg) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.50-1.80 (4H, m), 2.75-3.40 (4H, m), 2.99 (3H, s), 3.83 (3H, s), 3.05 -3.45 (4H, m), 3.96 (3H, s), 6.80-6.90 (3H, m), 6.96 (1H, d, J = 8.4Hz), 7.05-7.25 (2H, m), 7.80 (1H, dd , J = 8.4, 1.8Hz), 8.10 (1H, d, J = 1.8Hz).

Reference Example 102

参考例１３で得たN-[5-(5-クロロペンタノイル)-2-メトキシフェニル]メタンスルホンアミド(1.00g) および2-(2-クロロフェニル)エチルアミン(1.46g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.52g) を無色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.41(9H, s), 1.45-1.80(4H, m), 2.75-3.50(6H, m), 3.00(3H, s), 3.41(2H, t, J = 7.4Hz), 3.96(3H, s), 6.90-7.00(2H, m), 7.10-7.40(4H, m), 7.75-7.85(1H, m), 8.05-8.10(1H, m). 2- (2-Chlorophenyl) ethyl (5- {4-methoxy-3-[(methylsulfonyl) amino] phenyl} -5-oxopentyl) carbamate tert-butyl

Using N- [5- (5-chloropentanoyl) -2-methoxyphenyl] methanesulfonamide (1.00 g) and 2- (2-chlorophenyl) ethylamine (1.46 g) obtained in Reference Example 13, The same operation as in 19 was performed to give the title compound (1.52 g) as a colorless oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.45-1.80 (4H, m), 2.75-3.50 (6H, m), 3.00 (3H, s), 3.41 (2H, t, J = 7.4Hz), 3.96 (3H, s), 6.90-7.00 (2H, m), 7.10-7.40 (4H, m), 7.75-7.85 (1H, m), 8.05-8.10 (1H, m).

Reference Example 103

参考例１４で得たN-[5-(6-ブロモペンタノイル)-2-メトキシフェニル]メタンスルホンアミド(1.00g) およびフェネチルアミン(641mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(918mg) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.30-1.90(6H, m), 1.44(9H, s), 2.75-2.85(2H, m), 2.91(2H, t, J = 7.5Hz), 2.99(3H, s), 3.00-3.20(2H, m), 3.30-3.45(2H, m), 3.96(3H, s), 6.90(1H, s), 6.97(1H, d, J = 8.4Hz), 7.15-7.30(5H, m), 7.81(1H, dd, J = 8.4, 1.8Hz), 8.12(1H, d, J = 1.8Hz). 6- {4-Methoxy-3-[(methylsulfonyl) amino] phenyl} -6-oxohexyl (2-phenylethyl) carbamate tert-butyl

Perform the same operations as in Reference Example 19 using N- [5- (6-bromopentanoyl) -2-methoxyphenyl] methanesulfonamide (1.00 g) and phenethylamine (641 mg) obtained in Reference Example 14. Gave the title compound (918 mg) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.30-1.90 (6H, m), 1.44 (9H, s), 2.75-2.85 (2H, m), 2.91 (2H, t, J = 7.5Hz), 2.99 (3H , s), 3.00-3.20 (2H, m), 3.30-3.45 (2H, m), 3.96 (3H, s), 6.90 (1H, s), 6.97 (1H, d, J = 8.4Hz), 7.15- 7.30 (5H, m), 7.81 (1H, dd, J = 8.4, 1.8Hz), 8.12 (1H, d, J = 1.8Hz).

Reference Example 104

参考例１４で得たN-[5-(6-ブロモペンタノイル)-2-メトキシフェニル]メタンスルホンアミド(1.00g) および2-(2-メトキシフェニル)エチルアミン(800mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.00g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.25-1.60(4H, m), 1.43(9H, s), 1.73(2H, quintet, J = 7.5Hz), 2.75-2.90(2H, m), 2.91(2H, t, J = 7.5Hz), 2.99(3H, s), 3.00-3.20(2H, m), 3.30-3.45(2H, m), 3.82(3H, s), 3.96(3H, s), 6.80-7.20(6H, m), 7.80(1H, dd, J = 8.4, 1.8Hz), 8.10(1H, d, J = 1.8Hz). 6- {4-Methoxy-3-[(methylsulfonyl) amino] phenyl} -6-oxohexyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Using N- [5- (6-bromopentanoyl) -2-methoxyphenyl] methanesulfonamide (1.00 g) and 2- (2-methoxyphenyl) ethylamine (800 mg) obtained in Reference Example 14, The same operation as in 19 was performed to give the title compound (1.00 g) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.60 (4H, m), 1.43 (9H, s), 1.73 (2H, quintet, J = 7.5Hz), 2.75-2.90 (2H, m), 2.91 (2H , t, J = 7.5Hz), 2.99 (3H, s), 3.00-3.20 (2H, m), 3.30-3.45 (2H, m), 3.82 (3H, s), 3.96 (3H, s), 6.80- 7.20 (6H, m), 7.80 (1H, dd, J = 8.4, 1.8Hz), 8.10 (1H, d, J = 1.8Hz).

Reference Example 105

参考例１４で得たN-[5-(6-ブロモペンタノイル)-2-メトキシフェニル]メタンスルホンアミド(1.00g) および2-(2-クロロフェニル)エチルアミン(823mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.03g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.25-1.90(6H, m), 1.41(9H, s), 2.90-3.25(6H, m), 2.99(3H, s), 3.40(2H, t, J = 7.5Hz), 3.97(3H, s), 6.89(1H, s), 6.97(1H, d, J = 8.4Hz), 7.10-7.40(4H, m), 7.80(1H, dd, J = 8.4, 1.8Hz), 8.10(1H, d, J = 1.8Hz). 2- (2-Chlorophenyl) ethyl (6- {4-methoxy-3-[(methylsulfonyl) amino] phenyl} -6-oxohexyl) carbamate tert-butyl

Using N- [5- (6-bromopentanoyl) -2-methoxyphenyl] methanesulfonamide (1.00 g) and 2- (2-chlorophenyl) ethylamine (823 mg) obtained in Reference Example 14, Reference Example 19 The title compound (1.03 g) was obtained as a colorless oil by operations similar to those described above.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.90 (6H, m), 1.41 (9H, s), 2.90-3.25 (6H, m), 2.99 (3H, s), 3.40 (2H, t, J = 7.5Hz), 3.97 (3H, s), 6.89 (1H, s), 6.97 (1H, d, J = 8.4Hz), 7.10-7.40 (4H, m), 7.80 (1H, dd, J = 8.4, 1.8 Hz), 8.10 (1H, d, J = 1.8Hz).

Reference Example 106

参考例１５で得た5-クロロ-1-(1H-インドール-3-イル)-1-ペンタノン(1.00g) および2-フェニルエチルアミン(1.03g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点100-108℃の無色結晶(1.10g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.44(9H, s), 1.50-2.10(4H, m), 2.70-2.90(4H, m), 3.05-3.25(2H, m), 3.30-4.45(2H, m), 7.10-7.45(8H, m), 7.70-7.90(1H, m), 8.35-8.45(1H, m), 9.05-9.35(1H, br). 5- (1H-Indol-3-yl) -5-oxopentyl (2-phenylethyl) carbamate tert-butyl

Using 5-chloro-1- (1H-indol-3-yl) -1-pentanone (1.00 g) and 2-phenylethylamine (1.03 g) obtained in Reference Example 15, the same procedure as in Reference Example 19 was performed. This gave the title compound as colorless crystals (1.10 g) with a melting point of 100-108 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.50-2.10 (4H, m), 2.70-2.90 (4H, m), 3.05-3.25 (2H, m), 3.30-4.45 (2H, m), 7.10-7.45 (8H, m), 7.70-7.90 (1H, m), 8.35-8.45 (1H, m), 9.05-9.35 (1H, br).

Reference Example 107

参考例１５で得た5-クロロ-1-(1H-インドール-3-イル)-1-ペンタノン(1.00g) および2-(2-メトキシフェニル)エチルアミン(1.28g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(901mg) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.44(9H, s), 1.50-1.80(4H, m), 2.70-2.90(4H, m), 3.10-3.45(4H, m), 3.65-3.85(3H, m), 6.75-6.90(2H, m), 7.00-7.45(5H, m), 7.60-7.90(1H, m), 8.35-8.40(1H, m), 9.70-10.00(1H, br). 5- (1H-Indol-3-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Using 5-chloro-1- (1H-indol-3-yl) -1-pentanone (1.00 g) and 2- (2-methoxyphenyl) ethylamine (1.28 g) obtained in Reference Example 15, Reference Example 19 The title compound (901 mg) was obtained as a colorless oil by an operation similar to that described above.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.50-1.80 (4H, m), 2.70-2.90 (4H, m), 3.10-3.45 (4H, m), 3.65-3.85 (3H, m), 6.75-6.90 (2H, m), 7.00-7.45 (5H, m), 7.60-7.90 (1H, m), 8.35-8.40 (1H, m), 9.70-10.00 (1H, br).

Reference Example 108

参考例１５で得た5-クロロ-1-(1H-インドール-3-イル)-1-ペンタノン(1.00g) および2-(2-クロロフェニル)エチルアミン(1.32g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点97-99℃の無色結晶(1.10g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.42(9H, s), 1.50-1.80(4H, m), 2.70-3.50(6H, m), 3.41(2H, t, J = 7.5Hz), 7.05-7.45(7H, m), 7.65-7.90(1H, m), 8.35-8.45(1H, m), 9.20-9.40(1H, br). 2- (2-Chlorophenyl) ethyl [5- (1H-indol-3-yl) -5-oxopentyl] carbamate tert-butyl

Using 5-chloro-1- (1H-indol-3-yl) -1-pentanone (1.00 g) and 2- (2-chlorophenyl) ethylamine (1.32 g) obtained in Reference Example 15, By carrying out the same operation, the title compound was obtained as colorless crystals (1.10 g) having a melting point of 97-99 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.50-1.80 (4H, m), 2.70-3.50 (6H, m), 3.41 (2H, t, J = 7.5Hz), 7.05-7.45 (7H, m), 7.65-7.90 (1H, m), 8.35-8.45 (1H, m), 9.20-9.40 (1H, br).

Reference Example 109

参考例１６で得た6-ブロモ-1-(1H-インドール-3-イル)-1-ヘキサノン(1.00g) および2-フェニルエチルアミン(824mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点83-85℃の無色結晶(938mg)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.20-1.85(6H, m), 1.44(9H, s), 2.70-2.90(4H, m), 3.05-3.25(2H, m), 3.37(2H, t, J = 7.5Hz), 7.10-7.45(8H, m), 7.75-7.85(1H, m), 8.35-8.45(1H, m), 8.90-9.30(1H, br). Tert-Butyl 6- (1H-indol-3-yl) -6-oxohexyl (2-phenylethyl) carbamate

Using 6-bromo-1- (1H-indol-3-yl) -1-hexanone (1.00 g) and 2-phenylethylamine (824 mg) obtained in Reference Example 16, the same operation as in Reference Example 19 was performed. This gave the title compound as colorless crystals (938 mg) with a melting point of 83-85 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-1.85 (6H, m), 1.44 (9H, s), 2.70-2.90 (4H, m), 3.05-3.25 (2H, m), 3.37 (2H, t, J = 7.5Hz), 7.10-7.45 (8H, m), 7.75-7.85 (1H, m), 8.35-8.45 (1H, m), 8.90-9.30 (1H, br).

Reference Example 110

参考例１６で得た6-ブロモ-1-(1H-インドール-3-イル)-1-ヘキサノン(1.00g) および2-(2-メトキシフェニル)エチルアミン(1.03g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点133-135℃の無色結晶(788mg)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.20-1.85(6H, m), 1.43(9H, s), 2.70-2.90(4H, m), 3.05-3.25(2H, m), 3.34(2H, t, J = 7.2Hz), 3.79(3H, s), 6.75-6.90(2H, m), 7.00-7.45(5H, m), 7.75-7.85(1H, m), 8.35-8.45(1H, m), 9.15-9.40(1H, br). Tert-Butyl 6- (1H-indol-3-yl) -6-oxohexyl [2- (2-methoxyphenyl) ethyl] carbamate

Using 6-bromo-1- (1H-indol-3-yl) -1-hexanone (1.00 g) and 2- (2-methoxyphenyl) ethylamine (1.03 g) obtained in Reference Example 16, Reference Example 19 The title compound was obtained as colorless crystals (788 mg) with a melting point of 133-135 ° C. by carrying out the same operation as in.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-1.85 (6H, m), 1.43 (9H, s), 2.70-2.90 (4H, m), 3.05-3.25 (2H, m), 3.34 (2H, t, J = 7.2Hz), 3.79 (3H, s), 6.75-6.90 (2H, m), 7.00-7.45 (5H, m), 7.75-7.85 (1H, m), 8.35-8.45 (1H, m), 9.15 -9.40 (1H, br).

Reference Example 111

参考例１６で得た6-ブロモ-1-(1H-インドール-3-イル)-1-ヘキサノン(1.00g) および2-(2-クロロフェニル)エチルアミン(1.03g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点104-105℃の無色結晶(788mg)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.20-1.85(6H, m), 1.42(9H, s), 2.70-3.25(6H, m), 3.40(2H, t, J = 7.2Hz), 7.05-7.45(7H, m), 7.70-7.90(1H, m), 8.35-8.45(1H, m), 9.25-9.80(1H, br). 2- (2-Chlorophenyl) ethyl [6- (1H-indol-3-yl) -6-oxohexyl] carbamate tert-butyl

Using 6-bromo-1- (1H-indol-3-yl) -1-hexanone (1.00 g) and 2- (2-chlorophenyl) ethylamine (1.03 g) obtained in Reference Example 16, The same operation was performed to give the title compound as colorless crystals (788 mg) having a melting point of 104-105 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-1.85 (6H, m), 1.42 (9H, s), 2.70-3.25 (6H, m), 3.40 (2H, t, J = 7.2Hz), 7.05-7.45 (7H, m), 7.70-7.90 (1H, m), 8.35-8.45 (1H, m), 9.25-9.80 (1H, br).

Reference Example 112

参考例１７で得た5-クロロ-1-(2-チエニル)-1-ペンタノン(1.00g) および2-フェニルエチルアミン(1.19g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点49-50℃の無色結晶(1.08g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.44(9H, s), 1.45-1.80(4H, m), 2.75-2.95(4H, m), 3.05-3.45(4H, m), 7.10-7.35(6H, m), 7.12(1H, dd, J = 5.0, 0.9Hz), 7.71(1H, s). 5-Oxo-5- (2-thienyl) pentyl (2-phenylethyl) carbamate tert-butyl

Using 5-chloro-1- (2-thienyl) -1-pentanone (1.00 g) and 2-phenylethylamine (1.19 g) obtained in Reference Example 17, the same procedure as in Reference Example 19 was performed. The title compound was obtained as colorless crystals (1.08 g) with a melting point of 49-50 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.45-1.80 (4H, m), 2.75-2.95 (4H, m), 3.05-3.45 (4H, m), 7.10-7.35 (6H, m), 7.12 (1H, dd, J = 5.0, 0.9Hz), 7.71 (1H, s).

Reference Example 113

参考例１７で得た5-クロロ-1-(2-チエニル)-1-ペンタノン(1.00g) および2-(2-メトキシフェニル)エチルアミン(1.49g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.45g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.43(9H, s), 1.43-1.85(4H, m), 2.75-2.95(4H, m), 3.05-3.45(4H, m), 3.82(3H, s), 6.80-6.90(2H, m), 7.05-7.25(3H, m), 7.60-7.75(2H, m). 2- (2-Methoxyphenyl) ethyl [5-oxo-5- (2-thienyl) pentyl] carbamate tert-butyl

Using 5-chloro-1- (2-thienyl) -1-pentanone (1.00 g) and 2- (2-methoxyphenyl) ethylamine (1.49 g) obtained in Reference Example 17, the same procedure as in Reference Example 19 was performed. To give the title compound (1.45 g) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.43-1.85 (4H, m), 2.75-2.95 (4H, m), 3.05-3.45 (4H, m), 3.82 (3H, s) , 6.80-6.90 (2H, m), 7.05-7.25 (3H, m), 7.60-7.75 (2H, m).

Reference Example 114

参考例１７で得た5-クロロ-1-(2-チエニル)-1-ペンタノン(1.00g) および2-(2-クロロフェニル)エチルアミン(1.53g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.47g) を淡黄色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.41(9H, s), 1.45-1.80(4H, m), 2.85-3.30(4H, m), 3.05-3.30 (2H, m), 3.41(2H, t, J = 7.2Hz), 7.05-7.40(5H, m), 7.62(1H, dd, J = 5.0, 0.9Hz), 7.71(1H, s). 2- (2-Chlorophenyl) ethyl [5-oxo-5- (2-thienyl) pentyl] carbamate tert-butyl

Using 5-chloro-1- (2-thienyl) -1-pentanone (1.00 g) and 2- (2-chlorophenyl) ethylamine (1.53 g) obtained in Reference Example 17, the same procedure as in Reference Example 19 was performed. This gave the title compound (1.47g) as a pale yellow oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.45-1.80 (4H, m), 2.85-3.30 (4H, m), 3.05-3.30 (2H, m), 3.41 (2H, t, J = 7.2Hz), 7.05-7.40 (5H, m), 7.62 (1H, dd, J = 5.0, 0.9Hz), 7.71 (1H, s).

Reference Example 115

参考例１８で得た6-ブロモ-1-(2-チエニル)-1-ヘキサノン(1.00g) および2-フェニルエチルアミン(1.53g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.47g) を淡黄色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.25-1.60(4H, m), 1.44(9H, s), 1.75(2H, quintet, J = 7.5Hz), 2.75-2.90(2H, m), 2.89(2H, t, J = 7.5Hz), 3.05-3.25(2H, m), 3.50-3.65(2H, m), 7.12(1H, dd, J = 5.0, 3.6Hz), 7.15-7.35(5H, m), 7.61(1H, dd, J = 5.0, 0.9Hz), 7.70(1H, dd, J = 3.6, 0.9Hz). 6-oxo-6- (2-thienyl) hexyl (2-phenylethyl) carbamate tert-butyl

Using 6-bromo-1- (2-thienyl) -1-hexanone (1.00 g) and 2-phenylethylamine (1.53 g) obtained in Reference Example 18, the same operation as in Reference Example 19 was performed. The title compound (1.47 g) was obtained as a pale yellow oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.60 (4H, m), 1.44 (9H, s), 1.75 (2H, quintet, J = 7.5Hz), 2.75-2.90 (2H, m), 2.89 (2H , t, J = 7.5Hz), 3.05-3.25 (2H, m), 3.50-3.65 (2H, m), 7.12 (1H, dd, J = 5.0, 3.6Hz), 7.15-7.35 (5H, m), 7.61 (1H, dd, J = 5.0, 0.9Hz), 7.70 (1H, dd, J = 3.6, 0.9Hz).

Reference Example 116

参考例１８で得た6-ブロモ-1-(2-チエニル)-1-ヘキサノン(1.00g) および2-(2-メトキシフェニル)エチルアミン(1.16g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(884mg) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.20-1.65(4H, m), 1.43(9H, s), 1.70-1.85(2H, m), 2.75-2.90(2H, m), 2.89(2H, t, J = 7.2Hz), 3.05-3.25(2H, m), 3.25-3.40(2H, m), 3.82(3H, s), 6.83(1H, d, J = 7.5Hz), 6.88(1H, dd, J = 7.2, 0.9Hz), 7.05-7.25(2H, m), 7.12(1H, dd, J = 4.8, 3.9Hz), 7.62(1H, dd, J = 4.8, 1.2Hz), 7.70(1H, dd, J = 3.9, 1.2Hz). 2- (2-Methoxyphenyl) ethyl [6-oxo-6- (2-thienyl) hexyl] carbamate tert-butyl

Using 6-bromo-1- (2-thienyl) -1-hexanone (1.00 g) and 2- (2-methoxyphenyl) ethylamine (1.16 g) obtained in Reference Example 18, the same procedure as in Reference Example 19 was performed. To give the title compound (884 mg) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.20-1.65 (4H, m), 1.43 (9H, s), 1.70-1.85 (2H, m), 2.75-2.90 (2H, m), 2.89 (2H, t, J = 7.2Hz), 3.05-3.25 (2H, m), 3.25-3.40 (2H, m), 3.82 (3H, s), 6.83 (1H, d, J = 7.5Hz), 6.88 (1H, dd, J = 7.2, 0.9Hz), 7.05-7.25 (2H, m), 7.12 (1H, dd, J = 4.8, 3.9Hz), 7.62 (1H, dd, J = 4.8, 1.2Hz), 7.70 (1H, dd, J = 3.9, 1.2Hz).

Reference Example 117

参考例１８で得た6-ブロモ-1-(2-チエニル)-1-ヘキサノン(1.00g) および2-(2-メトキシフェニル)エチルアミン(1.19g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.07g) を無色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.25-1.65(4H, m), 1.43(9H, s), 1.65-1.85(2H, m), 2.80-3.25(4H, m), 2.89(2H, t, J = 7.5Hz), 3.40(2H, t, J = 7.5Hz), 7.05-7.40(5H, m), 7.60-7.75(2H, m). 2- (2-Chlorophenyl) ethyl [6-oxo-6- (2-thienyl) hexyl] carbamic acid tert-butyl

Using 6-bromo-1- (2-thienyl) -1-hexanone (1.00 g) and 2- (2-methoxyphenyl) ethylamine (1.19 g) obtained in Reference Example 18, the same procedure as in Reference Example 19 was performed. To give the title compound (1.07 g) as a colorless oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.25-1.65 (4H, m), 1.43 (9H, s), 1.65-1.85 (2H, m), 2.80-3.25 (4H, m), 2.89 (2H, t, J = 7.5Hz), 3.40 (2H, t, J = 7.5Hz), 7.05-7.40 (5H, m), 7.60-7.75 (2H, m).

Reference Example 118

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および(±)-1,2,3,4-テトラヒドロ-1-ナフタレニルアミン(755mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(528mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.10-2.10 (19H, m), 2.60-3.05(9H, m), 3.21(2H, t, J = 8.4Hz), 4.13(2H, t, J = 8.8Hz), 7.00-7.20(4H, m), 7.60-7.70(2H, m). (±) -5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl (1,2,3 , 4-Tetrahydro-1-naphthalenyl) carbamate tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and (±) obtained in Reference Example 1 The title compound (528 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using -1,2,3,4-tetrahydro-1-naphthalenylamine (755 mg).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.10-2.10 (19H, m), 2.60-3.05 (9H, m), 3.21 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.8Hz ), 7.00-7.20 (4H, m), 7.60-7.70 (2H, m).

Reference Example 119

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および(±)-1,2-ジフェニルエチルアミン(2.02g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(837mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.10-1.60(6H, m), 1.31(9H, s), 1.70-2.00(2H, m), 2.71(2H, t, J = 7.6Hz), 2.80-3.10(3H, m), 3.15-3.35(3H, m), 3.55-3.65(1H, m), 4.13(2H, t, J = 8.8Hz), 7.10-7.40(10H, m), 7.60-7.75(2H, m). (±) -1,2-Diphenylethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) Pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and (± ) -1,2-diphenylethylamine (2.02 g) was used in the same manner as in Reference Example 19 to give the title compound (837 mg) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.10-1.60 (6H, m), 1.31 (9H, s), 1.70-2.00 (2H, m), 2.71 (2H, t, J = 7.6Hz), 2.80-3.10 (3H, m), 3.15-3.35 (3H, m), 3.55-3.65 (1H, m), 4.13 (2H, t, J = 8.8Hz), 7.10-7.40 (10H, m), 7.60-7.75 (2H , m).

Reference Example 120

3-(トリフルオロアセチル)-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン(15.0g) および5-クロロバレリルクロリド(8.8ml) の1,2-ジクロロエタン(40ml) 溶液に、水冷下、塩化アルミニウム(17g, 130mmol) を少量ずつ加えた。室温で３０分攪拌後、反応溶液を氷(500g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、エタノール−ジエチルエーテルから結晶化することにより淡黄色固形物(15.2g) を得た。さらにエタノール−ジエチルエーテルから再結晶により、表題化合物を無色結晶(13.2g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.87-1.91 (4H, m), 2.97-3.08 (6H, m), 3.59 (2H, t, J = 6.2Hz), 3.70-3.81 (4H, m), 7.26 (1H, s), 7.75 (2H, m). 5-Chloro-1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone

To a solution of 3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3-benzazepine (15.0 g) and 5-chlorovaleryl chloride (8.8 ml) in 1,2-dichloroethane (40 ml), Aluminum chloride (17 g, 130 mmol) was added in small portions under water cooling. After stirring at room temperature for 30 minutes, the reaction solution was poured into ice (500 g), extracted with ethyl acetate, and washed with saturated brine. After drying the organic layer with magnesium sulfate, the solvent was distilled off under reduced pressure, and crystallization from ethanol-diethyl ether gave a pale yellow solid (15.2 g). Further, recrystallization from ethanol-diethyl ether gave the title compound as colorless crystals (13.2 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.87-1.91 (4H, m), 2.97-3.08 (6H, m), 3.59 (2H, t, J = 6.2Hz), 3.70-3.81 (4H, m), 7.26 (1H, s), 7.75 (2H, m).

Reference Example 121

参考例１２０で得た5-クロロ-1-[3-(トリフルオロアセチル)-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル]-1-ペンタノン(8.0g)のメタノール(40ml)−水(40ml) 溶液に、炭酸カリウム(9.2g, 66.3mmol) を加えた。室温で６０分攪拌後、溶媒を減圧下留去し、水(100g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去し、油状物(6.9g) を得た。
¹H NMR (200MHz, CDCl₃) δ 1.88 (4H, m), 2.35 (1H, br), 2.97 (10H, m), 3.58 (2H, m), 7.16-7.20 (1H, m), 7.69 (2H, m). 5-chloro-1- (2,3,4,5-tetrahydro-1H-3-benzazepine 7-yl) -1-pentanone

5-chloro-1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone (8.0 g) obtained in Reference Example 120 To a methanol (40 ml) -water (40 ml) solution, potassium carbonate (9.2 g, 66.3 mmol) was added. After stirring at room temperature for 60 minutes, the solvent was distilled off under reduced pressure, water (100 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure to give an oil (6.9 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.88 (4H, m), 2.35 (1H, br), 2.97 (10H, m), 3.58 (2H, m), 7.16-7.20 (1H, m), 7.69 (2H , m).

Reference Example 122

参考例１２１で得た5-クロロ-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン7-イル)-1-ペンタノン(2.2g)およびトリエチルアミン(1.67ml)のテトラヒドロフラン(30ml)溶液に、アセチルクロリド(679μl)を加えた。室温で６０分攪拌後、水(50g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去し、ついでシリカゲルカラムクロマトグラフィーにより精製し、油状物(2.54g) を得た。
¹H NMR (200MHz, CDCl₃) δ 1.89 (4H, m), 2.19 (3H, s), 2.99 (6H, m), 3.59 (4H, m), 3.74 (2H, m), 7.21-7.27 (1H, m), 7.74(2H, m). 1- (3-acetyl-2,3,4,5-tetrahydro-1H-3-benzazepine 7-yl) -5-chloro-1-pentanone

5-Chloro-1- (2,3,4,5-tetrahydro-1H-3-benzazepine 7-yl) -1-pentanone (2.2 g) obtained in Reference Example 121 and triethylamine (1.67 ml) in tetrahydrofuran (30 ml) Acetyl chloride (679 μl) was added to the solution. After stirring at room temperature for 60 minutes, water (50 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. After drying the organic layer with sodium sulfate, the solvent was distilled off under reduced pressure, and then the residue was purified by silica gel column chromatography to obtain an oil (2.54 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.89 (4H, m), 2.19 (3H, s), 2.99 (6H, m), 3.59 (4H, m), 3.74 (2H, m), 7.21-7.27 (1H , m), 7.74 (2H, m).

Reference Example 123

参考例１２１で得た5-クロロ-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン7-イル)-1-ペンタノン(2.4g)およびトリエチルアミン(1.67ml)のテトラヒドロフラン(30ml)溶液に、メチルスルホニルクロリド(804μl)を加えた。室温で６０分攪拌後、水(50g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去することにより淡黄色固形物(2.2g) を得た。さらにエタノール−ジエチルエーテルからの再結晶により、表題化合物を無色結晶(1.92g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.89 (4H, m), 2.80 (3H, s), 2.99 (2H, m), 3.08 (4H, m), 3.46 (4H, m), 3.59 (2H, m), 7.23-7.25 (1H, m), 7.74(2H, m). 5-Chloro-1- [3- (methylsulfonyl) -2,3,4,5-tetrahydro-1H-3-benzazepine 7-yl] -1-pentanone

5-Chloro-1- (2,3,4,5-tetrahydro-1H-3-benzazepine 7-yl) -1-pentanone (2.4 g) and triethylamine (1.67 ml) obtained in Reference Example 121 in tetrahydrofuran (30 ml) ) To the solution was added methylsulfonyl chloride (804 μl). After stirring at room temperature for 60 minutes, water (50 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a pale yellow solid (2.2 g). Further, recrystallization from ethanol-diethyl ether gave the title compound as colorless crystals (1.92 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.89 (4H, m), 2.80 (3H, s), 2.99 (2H, m), 3.08 (4H, m), 3.46 (4H, m), 3.59 (2H, m ), 7.23-7.25 (1H, m), 7.74 (2H, m).

Reference Example 124

参考例１２１で得た5-クロロ-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン7-イル)-1-ペンタノン(2.3g)のテトラヒドロフラン(30ml)溶液に、エチルイソシアネート(781μl)を加えた。室温で６０分攪拌後、水(50g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去することにより無色固形物(2.2g) を得た。
¹H NMR (200MHz, CDCl₃) δ 1.17 (3H, t, J = 7.0Hz), 1.89 (4H, m), 2.99 (6H, m), 3.32 (2H, q, J = 7.0Hz), 3.56 (6H, m), 4.47 (1H, m), 7.19-7.23 (1H, m), 7.71(2H, m). 7- (5-Chloropentanoyl) -N-ethyl-1,2,4,5-tetrahydro-3H-3-benzazepine 3-carboxamide

Ethyl isocyanate was added to a solution of 5-chloro-1- (2,3,4,5-tetrahydro-1H-3-benzazepine 7-yl) -1-pentanone (2.3 g) obtained in Reference Example 121 in tetrahydrofuran (30 ml). (781 μl) was added. After stirring at room temperature for 60 minutes, water (50 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure to give a colorless solid (2.2 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.17 (3H, t, J = 7.0Hz), 1.89 (4H, m), 2.99 (6H, m), 3.32 (2H, q, J = 7.0Hz), 3.56 ( 6H, m), 4.47 (1H, m), 7.19-7.23 (1H, m), 7.71 (2H, m).

Reference Example 125

参考例１２１で得た2-アセチル-1,2,3,4-テトラヒドロイソキノリン(15.0g) および5-クロロバレリルクロリド(12.0ml) の1,2-ジクロロエタン(50ml) 溶液に、水冷下、塩化アルミニウム(24g, 181mmol) を少量ずつ加えた。室温で３０分攪拌後、反応溶液を氷(500g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより淡黄色固形物(14.2g) を得た。さらにエタノール−ジエチルエーテルからの再結晶により、表題化合物を無色結晶(12.5g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.76 (4H, m), 2.09 (3H, s), 2.86 (2H, t, J = 5.8Hz), 3.04 (2H, t, J = 6.0Hz), 3.67 (4H, m), 4.66 (2H, s), 7.30 (1H, s), 7.74(2H, m). 1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-chloro-1-pentanone

To a solution of 2-acetyl-1,2,3,4-tetrahydroisoquinoline (15.0 g) and 5-chlorovaleryl chloride (12.0 ml) obtained in Reference Example 121 in 1,2-dichloroethane (50 ml) under water cooling, Aluminum chloride (24 g, 181 mmol) was added in small portions. After stirring at room temperature for 30 minutes, the reaction solution was poured into ice (500 g), extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain a pale yellow solid (14.2 g). Further, recrystallization from ethanol-diethyl ether gave the title compound as colorless crystals (12.5 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.76 (4H, m), 2.09 (3H, s), 2.86 (2H, t, J = 5.8Hz), 3.04 (2H, t, J = 6.0Hz), 3.67 (4H, m), 4.66 (2H, s), 7.30 (1H, s), 7.74 (2H, m).

Reference Example 126

オルトフェニレンジアミン(20g) およびスルファミド(20.4g) のジグライム(200ml) 溶液を１６０℃で２時間攪拌後、反応溶液を室温に戻し、水(200g) を注ぎ、次いでpH1になるまで塩酸を加え、酢酸エチルで抽出、１規定塩酸で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、赤褐色固形物(14.2g) を得た。さらにエタノール−ジエチルエーテルからの再結晶により、表題化合物を無色結晶(13.2g)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 6.77-6.91 (4H, m), 10.95 (2H, s). 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

After stirring a solution of orthophenylenediamine (20 g) and sulfamide (20.4 g) in diglyme (200 ml) at 160 ° C. for 2 hours, the reaction solution is returned to room temperature, poured into water (200 g), and then hydrochloric acid is added until pH 1 is reached. Extracted with ethyl acetate and washed with 1N hydrochloric acid. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain a reddish brown solid (14.2 g). Further, recrystallization from ethanol-diethyl ether gave the title compound as colorless crystals (13.2 g).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 6.77-6.91 (4H, m), 10.95 (2H, s).

Reference Example 127

参考例１２６で得た1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール 2,2-ジオキシド(10g)のジメチルホルムアミド(100ml) 溶液に水素化ナトリウム(5g)を加え、室温で1時間攪拌後、ヨウ化メチルを加え、室温で１８時間攪拌した。反応溶液に水(200g) を注ぎ、酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、赤褐色固形物(9.9g) を得た。さらに水−酢酸エチルから再結晶により、表題化合物を無色結晶(9.0ｇ)として得た。
¹H NMR (200MHz, CDCl₃) δ 3.28 (6H, s), 6.74 (2H, q, J = 3.2Hz), 7.00 (2H, q, J = 3.4Hz). 1,3-dimethyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

Sodium hydride (5 g) was added to a solution of 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (10 g) obtained in Reference Example 126 in dimethylformamide (100 ml) and stirred at room temperature for 1 hour. Thereafter, methyl iodide was added, and the mixture was stirred at room temperature for 18 hours. Water (200 g) was poured into the reaction solution, extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain a reddish brown solid (9.9 g). Further, recrystallization from water-ethyl acetate gave the title compound as colorless crystals (9.0 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 3.28 (6H, s), 6.74 (2H, q, J = 3.2Hz), 7.00 (2H, q, J = 3.4Hz).

Reference Example 128

参考例１２６で得た1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール 2,2-ジオキシドおよび5-クロロバレリルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.75 (4H, m), 3.03 (2H, t, J = 6.6Hz), 3.68 (2H, t, J = 6.2Hz), 6.89 (1H, d, J = 8.4Hz), 7.33 (1H, s), 7.62 (1H, d, J = 8.4Hz), 11.54 (2H, br). 5-Chloro-1- (2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone

The title compound was obtained by the same procedures as in Reference Example 1 using 1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 5-chlorovaleryl chloride obtained in Reference Example 126. Was obtained as colorless crystals.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.75 (4H, m), 3.03 (2H, t, J = 6.6Hz), 3.68 (2H, t, J = 6.2Hz), 6.89 (1H, d, J = 8.4 Hz), 7.33 (1H, s), 7.62 (1H, d, J = 8.4Hz), 11.54 (2H, br).

Reference Example 129

参考例１２７で得た1,3-ジメチル-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール 2,2-ジオキシドおよび5-クロロバレリルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.89 (4H, m), 2.99 (2H, t, J = 7.0Hz), 3.35 (6H, s), 3.60 (2H, t, J = 6.2Hz), 6.75 (1H, d, J = 8.4Hz), 7.39 (1H, s), 7.69 (1H, d, J = 8.4Hz). 5-Chloro-1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone

Using 1,3-dimethyl-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide and 5-chlorovaleryl chloride obtained in Reference Example 127, the same procedure as in Reference Example 1 was performed. This gave the title compound as colorless crystals.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.89 (4H, m), 2.99 (2H, t, J = 7.0Hz), 3.35 (6H, s), 3.60 (2H, t, J = 6.2Hz), 6.75 ( 1H, d, J = 8.4Hz), 7.39 (1H, s), 7.69 (1H, d, J = 8.4Hz).

Reference Example 130

８−ニトロキノリン (25.0g)、酸化白金(600mg) および氷酢酸(300ml) 混合溶液を５気圧の水素雰囲気下、室温で４時間攪拌した。反応溶液をセライトでろ過し、溶媒を減圧下留去した。次いで、酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、シリカゲルカラムクロマトグラフィーで精製し、表題化合物を赤褐色油状物(15.2g) として得た。
¹H NMR (200MHz, CDCl₃) δ 1.96 (2H, quint, J = 2.6Hz), 2.76 (2H, t, J = 6.2Hz), 3.56 (3H, br), 3.32 (2H, t, J = 5.6Hz), 6.53 (3H, m). 1,2,3,4-tetrahydro-8-quinolinamine

A mixed solution of 8-nitroquinoline (25.0 g), platinum oxide (600 mg) and glacial acetic acid (300 ml) was stirred at room temperature for 4 hours under a hydrogen atmosphere of 5 atm. The reaction solution was filtered through celite, and the solvent was evaporated under reduced pressure. Next, the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the title compound as a reddish brown oil (15.2 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.96 (2H, quint, J = 2.6Hz), 2.76 (2H, t, J = 6.2Hz), 3.56 (3H, br), 3.32 (2H, t, J = 5.6 Hz), 6.53 (3H, m).

Reference Example 131

参考例１３０で得た1,2,3,4-テトラヒドロ-8-キノリンアミン(10g)のテトラヒドロフラン(100ml) 溶液に1,1'-カルボニルジイミダゾールのテトラヒドロフラン懸濁液を加え、室温で４時間攪拌した。反応溶液を濃縮し、褐色固形物(11g)を得た。さらに水−酢酸エチルからの再結晶により、表題化合物を無色結晶(10g)として得た。
¹H NMR (200MHz, CDCl₃) δ 2.00 (2H, t, J = 5.4Hz), 2.76 (2H, t, J = 5.8Hz), 3.69 (2H, t, J = 5.6Hz), 6.80 (3H, m), 10.61 (1H, s). 5,6-Dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one

To a solution of 1,2,3,4-tetrahydro-8-quinolinamine (10 g) obtained in Reference Example 130 in tetrahydrofuran (100 ml) was added a tetrahydrofuran suspension of 1,1′-carbonyldiimidazole, and the mixture was stirred at room temperature for 4 hours. Stir. The reaction solution was concentrated to give a brown solid (11 g). Furthermore, recrystallization from water-ethyl acetate gave the title compound as colorless crystals (10 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 2.00 (2H, t, J = 5.4Hz), 2.76 (2H, t, J = 5.8Hz), 3.69 (2H, t, J = 5.6Hz), 6.80 (3H, m), 10.61 (1H, s).

Reference Example 132

参考例１３１で得た5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オン(10g)のジメチルホルムアミド(100ml) 溶液に水素化ナトリウム(2.36g)を加え、室温で1時間攪拌後、ヨウ化メチル(3.68ml)を加え、室温で１８時間攪拌した。反応溶液に水(200g) を注ぎ、酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、淡黄色固形物(9.7g) を得た。さらに水−酢酸エチルから再結晶により、表題化合物を無色結晶(9.0ｇ)として得た。
¹H NMR (200MHz, CDCl₃) δ 2.12 (2H, quint, J = 6.4Hz), 2.86 (2H, t, J = 6.2Hz), 3.41 (3H, s), 3.87 (2H, t, J = 5.8Hz), 6.79-7.04 (3H, m). 1-Methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one

Sodium hydride (2.36 g) was added to a solution of 5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one (10 g) obtained in Reference Example 131 in dimethylformamide (100 ml). After stirring at room temperature for 1 hour, methyl iodide (3.68 ml) was added and stirred at room temperature for 18 hours. Water (200 g) was poured into the reaction solution, extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain a pale yellow solid (9.7 g). Further, recrystallization from water-ethyl acetate gave the title compound as colorless crystals (9.0 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 2.12 (2H, quint, J = 6.4Hz), 2.86 (2H, t, J = 6.2Hz), 3.41 (3H, s), 3.87 (2H, t, J = 5.8 Hz), 6.79-7.04 (3H, m).

Reference Example 133

参考例１３１で得た5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよび5-クロロバレリルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.75 (4H, m), 2.00 (2H, m), 2.81 (2H, m), 3.06 (2H, m), 3.72 (4H, m), 6.91 (1H, m), 7.65 (1H, m), 10.92 (1H, s). 8- (5-Chloropentanoyl) -5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one

The same operation as in Reference Example 1 using 5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and 5-chlorovaleryl chloride obtained in Reference Example 131 To give the title compound as colorless crystals.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.75 (4H, m), 2.00 (2H, m), 2.81 (2H, m), 3.06 (2H, m), 3.72 (4H, m), 6.91 (1H , m), 7.65 (1H, m), 10.92 (1H, s).

Reference Example 134

参考例１３２で得た1-メチル-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよび5-クロロバレリルクロリドを用いて、参考例１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.85-1.93 (4H, m), 2.09 (2H, m), 2.88 (1H, m), 3.00 (2H, m), 3.23 (1H, m), 3.45 (3H, s), 3.59 (2H, m), 3.86 (2H, m), 6.87 (1H, t, J = 8.4Hz), 7.62 (1H, t, J = 8.4Hz). 8- (5-Chloropentanoyl) -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one

Using 1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and 5-chlorovaleryl chloride obtained in Reference Example 132, Reference Example 1 The title compound was obtained as colorless crystals by operations similar to those described above.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.85-1.93 (4H, m), 2.09 (2H, m), 2.88 (1H, m), 3.00 (2H, m), 3.23 (1H, m), 3.45 (3H , s), 3.59 (2H, m), 3.86 (2H, m), 6.87 (1H, t, J = 8.4Hz), 7.62 (1H, t, J = 8.4Hz).

Reference Example 135

参考例１０で得た1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(25 g, 154 mmol)と無水コハク酸 (15.4 g, 154 mmol) のジクロロエタン混合物に水冷下、塩化アルミニウム(62 g, 462 mmol)を少量ずつ加えた。室温で３０分攪拌後、反応溶液を氷(500g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、エタノール−ジエチルエーテルから結晶化することにより表題化合物を無色結晶(25.0g) として得た。
¹H NMR (200MHz, DMSO-d₆) δ 2.59 (2H, t, J = 6.4Hz), 3.28 (2H, t, J = 6.2Hz), 3.36 (3H, s), 3.38 (3H, s), 7.24 (1H, d, J = 8.4Hz), 7.73 (1H, s), 7.78 (1H, d, J = 8.4Hz), 12.01 (1H, br). 4- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -4-oxobutanoic acid

To a dichloroethane mixture of 1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one (25 g, 154 mmol) and succinic anhydride (15.4 g, 154 mmol) obtained in Reference Example 10 under water cooling Aluminum chloride (62 g, 462 mmol) was added in small portions. After stirring at room temperature for 30 minutes, the reaction solution was poured into ice (500 g), extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure and crystallized from ethanol-diethyl ether to give the title compound as colorless crystals (25.0 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 2.59 (2H, t, J = 6.4Hz), 3.28 (2H, t, J = 6.2Hz), 3.36 (3H, s), 3.38 (3H, s), 7.24 (1H, d, J = 8.4Hz), 7.73 (1H, s), 7.78 (1H, d, J = 8.4Hz), 12.01 (1H, br).

Reference Example 136

参考例１３５で得た4-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-4-オキソブタン酸(25 g, 101 mmol)、10％パラジウム炭素(2 g)および 濃塩酸(3 ml)の酢酸溶液を5気圧の水素圧雰囲気下、室温で５時間攪拌後、反応溶液をセライトろ過し、パラジウム炭素を取り除いた。溶媒を減圧下留去し、エタノール−ジエチルエーテルから結晶化することにより表題化合物を無色結晶(20.0g) として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.81 (2H, quint, J = 7.0Hz), 2.22 (2H, t, J = 7.4Hz), 2.63 (2H, t, J = 7.4Hz), 3.30 (3H, s), 3.31 (3H, s), 6.86-7.05 (3H, m), 12.01 (1H, br). 4- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) butanoic acid

4- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -4-oxobutanoic acid (25 g, 101 mmol), 10% palladium obtained in Reference Example 135 An acetic acid solution of carbon (2 g) and concentrated hydrochloric acid (3 ml) was stirred at room temperature for 5 hours under a hydrogen pressure atmosphere of 5 atm. The reaction solution was filtered through Celite to remove palladium on carbon. The solvent was distilled off under reduced pressure, and crystallization from ethanol-diethyl ether gave the title compound as colorless crystals (20.0 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.81 (2H, quint, J = 7.0Hz), 2.22 (2H, t, J = 7.4Hz), 2.63 (2H, t, J = 7.4Hz), 3.30 ( 3H, s), 3.31 (3H, s), 6.86-7.05 (3H, m), 12.01 (1H, br).

Reference Example 137

参考例１３６で得た4-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)ブタン酸(20 g, 81 mmol)とジメチルホルムアミド (１ml) のテトラヒドロフラン溶液に水冷下、オギザリルクロリド(7.0 ml, 81 mmol)を少量ずつ滴下した。室温で３０分攪拌後、反応溶液を濃縮し、次いで反応残渣をニトロエタンに溶かし、水冷下、塩化アルミニウム(21.6 g, 162 mmol)を少量ずつ加えた。室温で３０分攪拌後、反応溶液を氷(500g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、エタノール−ジエチルエーテルから結晶化することにより表題化合物を無色結晶(18.0g) として得た。
¹H NMR (200MHz, DMSO-d₆) δ 2.15 (2H, quint, J = 6.6Hz), 2.67 (2H, t, J = 7.4Hz), 3.02 (2H, t, J = 7.4Hz), 3.43 (3H, s), 3.44 (3H, s), 6.79 (1H, s), 7.67 (1H, s). 1,3-Dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5-dione

4- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) butanoic acid (20 g, 81 mmol) obtained in Reference Example 136 and dimethylformamide (1 ml) Ogitalyl chloride (7.0 ml, 81 mmol) was added dropwise to the tetrahydrofuran solution little by little under water cooling. After stirring at room temperature for 30 minutes, the reaction solution was concentrated, then the reaction residue was dissolved in nitroethane, and aluminum chloride (21.6 g, 162 mmol) was added in small portions under water cooling. After stirring at room temperature for 30 minutes, the reaction solution was poured into ice (500 g), extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure and crystallized from ethanol-diethyl ether to give the title compound as colorless crystals (18.0 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 2.15 (2H, quint, J = 6.6Hz), 2.67 (2H, t, J = 7.4Hz), 3.02 (2H, t, J = 7.4Hz), 3.43 ( 3H, s), 3.44 (3H, s), 6.79 (1H, s), 7.67 (1H, s).

Reference Example 138

60％油性水素化ナトリウム(6 g)をn-ヘキサン(30 mlを二回)で洗浄し、デカンテーションにより溶媒を除いた後、テトラヒドロフラン(200 ml)、続いて炭酸ジエチル(9.8 g)を加え、緩やかに還流した。該懸濁液に、参考例１３７で得た1,3-ジメチル-3,6,7,8-テトラヒドロ-1H-ナフト[2,3-d]イミダゾール-2,5-ジオン(10 g, 43.4 mmol)の熱テトラヒドロフラン溶液を還流を維持するように滴下した。混合物を18時間還流した後、放冷し、酢酸(18 ml)を注意深く滴下して、過剰の水素化ナトリウムを分解した。さらに、水を加え、酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、エタノール−ジエチルエーテルから結晶化することにより表題化合物を無色結晶(7.0g) として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.21 (3H, t, J = 6.8Hz), 2.27 (2H, quint, J = 6.6Hz), 3.02 (2H, m), 3.31 (3H, s), 3.33 (3H, s), 3.72 (1H, dd, J = 9.6, 5.8Hz), 4.15 (2H, q, J = 7.0Hz), 7.09 (1H, s), 7.55 (1H, s). (±) -1,3-Dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2,3-d] imidazole-6-carboxylate

Wash 60% oily sodium hydride (6 g) with n-hexane (twice 30 ml), remove the solvent by decantation, add tetrahydrofuran (200 ml), and then add diethyl carbonate (9.8 g). Gently refluxed. To the suspension, 1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5-dione (10 g, 43.4) obtained in Reference Example 137 was added. mmol) of hot tetrahydrofuran was added dropwise to maintain reflux. The mixture was refluxed for 18 hours, then allowed to cool and acetic acid (18 ml) was carefully added dropwise to decompose excess sodium hydride. Furthermore, water was added, extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was crystallized from ethanol-diethyl ether to give the title compound as colorless crystals (7.0 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.21 (3H, t, J = 6.8Hz), 2.27 (2H, quint, J = 6.6Hz), 3.02 (2H, m), 3.31 (3H, s), 3.33 (3H, s), 3.72 (1H, dd, J = 9.6, 5.8Hz), 4.15 (2H, q, J = 7.0Hz), 7.09 (1H, s), 7.55 (1H, s).

Reference Example 139

参考例１３８で得た(±)-1,3-ジメチル-2,5-ジオキソ-2,3,5,6,7,8-ヘキサヒドロ-1H-ナフト[2,3-d]イミダゾール-6-カルボン酸エチル(5.0g)のジメチルホルムアミド溶液に60％油性水素化ナトリウム(832 mg)を加え、60℃で1時間攪拌後、1−ブロモ−3−クロロプロパンを加え、さらに60℃で4時間攪拌した。反応溶液を放冷し、水を加え、過剰の水素化ナトリウムを分解した。次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、シリカゲルカラムクロマトグラフィーにて精製することにより表題化合物を淡黄色油状物として得た。
MS m/z: 379 [M+H]⁺ (±) -6- (3-Chloropropyl) -1,3-dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2,3-d] imidazole Ethyl-6-carboxylate

(±) -1,3-Dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2,3-d] imidazole-6- obtained in Reference Example 138 Add 60% oily sodium hydride (832 mg) to a solution of ethyl carboxylate (5.0 g) in dimethylformamide, stir at 60 ° C. for 1 hour, add 1-bromo-3-chloropropane, and stir at 60 ° C. for 4 hours. did. The reaction solution was allowed to cool and water was added to decompose excess sodium hydride. Next, the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a pale yellow oil.
MS m / z: 379 [M + H] ⁺

Reference Example 140

参考例１３８で得た(±)-1,3-ジメチル-2,5-ジオキソ-2,3,5,6,7,8-ヘキサヒドロ-1H-ナフト[2,3-d]イミダゾール-6-カルボン酸エチルおよび1−ブロモ−4−クロロブタンを用いて、参考例１３９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
MS m/z: 393 [M+H]⁺ (±) -6- (4-Chlorobutyl) -1,3-dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2,3-d] imidazole- 6-Carboxylic acid ethyl ester

(±) -1,3-Dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2,3-d] imidazole-6- obtained in Reference Example 138 The title compound was obtained as a pale-yellow oil by the same procedures as in Reference Example 139 using ethyl carboxylate and 1-bromo-4-chlorobutane.
MS m / z: 393 [M + H] ⁺

Reference Example 141

参考例１３９で得た(±)-6-(3-クロロプロピル)-1,3-ジメチル-2,5-ジオキソ-2,3,5,6,7,8-ヘキサヒドロ-1H-ナフト[2,3-d]イミダゾール-6-カルボン酸エチルの濃塩酸(130 ml)溶液を130℃で3時間還流した。反応溶液を放冷し、炭酸カリウムで中和し、ついで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより表題化合物を淡黄色油状物として得た。
MS m/z: 307 [M+H]⁺ (±) -6- (3-Chloropropyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5-dione

(±) -6- (3-Chloropropyl) -1,3-dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2] obtained in Reference Example 139 A solution of ethyl, 3-d] imidazole-6-carboxylate in concentrated hydrochloric acid (130 ml) was refluxed at 130 ° C. for 3 hours. The reaction solution was allowed to cool, neutralized with potassium carbonate, extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as a pale yellow oil.
MS m / z: 307 [M + H] ⁺

Reference Example 142

参考例１４０で得た(±)-6-(4-クロロブチル)-1,3-ジメチル-2,5-ジオキソ-2,3,5,6,7,8-ヘキサヒドロ-1H-ナフト[2,3-d]イミダゾール-6-カルボン酸エチルを用いて、参考例１４１と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
MS m/z: 321 [M+H]⁺ (±) -6- (4-Chlorobutyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5-dione

(±) -6- (4-Chlorobutyl) -1,3-dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2, obtained in Reference Example 140 The title compound was obtained as a pale-yellow oil by the same procedures as in Reference Example 141 using ethyl 3-d] imidazole-6-carboxylate.
MS m / z: 321 [M + H] ⁺

Reference Example 143

5,6-ジメトキシ-1-インダノンを用いて、参考例１３８と同様の操作を行うことにより、表題化合物を融点140-141℃の淡黄色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.32 (3H, t, J = 6.8Hz), 3.27 (1H, dd, J = 17.2, 8.0Hz), 3.45 (1H, dd, J = 17.2, 3.6Hz), 3.70 (1H, q, J = 3.6Hz), 3.91 (3H, s), 3.99 (3H, s), 4.27 (2H, q, J = 6.8Hz), 6.92 (1H, s), 7.18 (1H, s). (±) -5,6-Dimethoxy-1-oxo-2-indanecarboxylic acid ethyl ester

The title compound was obtained as pale-yellow crystals with a melting point of 140-141 ° C. by conducting the same operation as in Reference Example 138 using 5,6-dimethoxy-1-indanone.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.32 (3H, t, J = 6.8Hz), 3.27 (1H, dd, J = 17.2, 8.0Hz), 3.45 (1H, dd, J = 17.2, 3.6Hz), 3.70 (1H, q, J = 3.6Hz), 3.91 (3H, s), 3.99 (3H, s), 4.27 (2H, q, J = 6.8Hz), 6.92 (1H, s), 7.18 (1H, s ).

Reference Example 144

参考例１４３で得た(±)-5,6-ジメトキシ-1-オキソ-2-インダンカルボン酸エチルを用いて、参考例１３９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.22 (3H, t, J = 6.8Hz), 1.73 (2H, m), 2.00 (1H, m), 2.24 (1H, m), 2.98 (1H, d, J = 17.2Hz), 3.38 (1H, t, J = 6.6Hz), 3.54 (1H, t, J = 6.6Hz), 3.61 (1H, d, J = 17.2Hz), 3.91 (3H, s), 3.99 (3H, s), 4.17 (2H, q, J = 6.8Hz), 6.90 (1H, s), 7.16 (1H, s). (±) -2- (3-Chloropropyl) -5,6-dimethoxy-1-oxo-2-indanecarboxylic acid ethyl ester

The title compound was obtained as a pale yellow oil by performing the same operation as in Reference Example 139, using ethyl (±) -5,6-dimethoxy-1-oxo-2-indanecarboxylate obtained in Reference Example 143. Obtained.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.22 (3H, t, J = 6.8Hz), 1.73 (2H, m), 2.00 (1H, m), 2.24 (1H, m), 2.98 (1H, d, J = 17.2Hz), 3.38 (1H, t, J = 6.6Hz), 3.54 (1H, t, J = 6.6Hz), 3.61 (1H, d, J = 17.2Hz), 3.91 (3H, s), 3.99 ( 3H, s), 4.17 (2H, q, J = 6.8Hz), 6.90 (1H, s), 7.16 (1H, s).

Reference Example 145

参考例１４３で得た(±)-5,6-ジメトキシ-1-オキソ-2-インダンカルボン酸エチルおよび1−ブロモ−4−クロロブタンを用いて、参考例１３９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.23 (3H, t, J = 7.6Hz), 1.30-1.46 (2H, m), 1.75-1.94 (3H, m), 2.14 (1H, m), 3.00 (1H, d, J = 17.2Hz), 3.39 (1H, t, J = 6.6Hz), 3.51 (1H, t, J = 6.6Hz), 3.62 (1H, d, J = 17.2Hz), 3.91 (3H, s), 3.99 (3H, s), 4.18 (2H, q, J = 7.6Hz), 6.91 (1H, s), 7.17 (1H, s). (±) -2- (3-Chlorobutyl) -5,6-dimethoxy-1-oxo-2-indanecarboxylic acid ethyl ester

By performing the same operation as in Reference Example 139 using ethyl (±) -5,6-dimethoxy-1-oxo-2-indanecarboxylate obtained in Reference Example 143 and 1-bromo-4-chlorobutane, The title compound was obtained as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.23 (3H, t, J = 7.6Hz), 1.30-1.46 (2H, m), 1.75-1.94 (3H, m), 2.14 (1H, m), 3.00 (1H , d, J = 17.2Hz), 3.39 (1H, t, J = 6.6Hz), 3.51 (1H, t, J = 6.6Hz), 3.62 (1H, d, J = 17.2Hz), 3.91 (3H, s ), 3.99 (3H, s), 4.18 (2H, q, J = 7.6Hz), 6.91 (1H, s), 7.17 (1H, s).

Reference Example 146

参考例１４４で得た(±)-2-(3-クロロプロピル)-5,6-ジメトキシ-1-オキソ-2-インダンカルボン酸エチルを用いて、参考例１４１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.65 (2H, m), 1.95 (2H, m), 2.65-2.77 (2H, m), 3.29 (1H, dd, J = 17.1, 7.8Hz), 3.59 (2H, m), 3.91 (3H, s), 3.97 (3H, s), 6.87 (1H, s), 7.16 (1H, s). (±) -2- (3-Chloropropyl) -5,6-dimethoxy-1-indanone

By performing the same operation as in Reference Example 141 using ethyl (±) -2- (3-chloropropyl) -5,6-dimethoxy-1-oxo-2-indanecarboxylate obtained in Reference Example 144 The title compound was obtained as colorless crystals.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.65 (2H, m), 1.95 (2H, m), 2.65-2.77 (2H, m), 3.29 (1H, dd, J = 17.1, 7.8Hz), 3.59 (2H m), 3.91 (3H, s), 3.97 (3H, s), 6.87 (1H, s), 7.16 (1H, s).

Reference Example 147

参考例１４５で得た(±)-2-(3-クロロブチル)-5,6-ジメトキシ-1-オキソ-2-インダンカルボン酸エチルを用いて、参考例１４１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.42-1.98 (6H, m), 2.62-2.79 (2H, m), 3.28 (1H, dd, J = 17.2, 7.4Hz), 3.56 (2H, t, J = 6.6Hz), 3.91 (3H, s), 3.97 (3H, s), 6.88 (1H, s), 7.18 (1H, s). (±) -2- (4-Chlorobutyl) -5,6-dimethoxy-1-indanone

By performing the same operation as in Reference Example 141 using ethyl (±) -2- (3-chlorobutyl) -5,6-dimethoxy-1-oxo-2-indanecarboxylate obtained in Reference Example 145, The title compound was obtained as colorless crystals.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.42-1.98 (6H, m), 2.62-2.79 (2H, m), 3.28 (1H, dd, J = 17.2, 7.4Hz), 3.56 (2H, t, J = 6.6Hz), 3.91 (3H, s), 3.97 (3H, s), 6.88 (1H, s), 7.18 (1H, s).

Reference Example 148

参考例１２８で得た5-クロロ-1-(2,2-ジオキシド-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール-5-イル)-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
MS m/z: 508 [M+H]⁺ 2- (2-Chlorophenyl) ethyl [5- (2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -5-oxopentyl] carbamate tert-butyl

5-Chloro-1- (2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone and 2- (2-chlorophenyl) obtained in Reference Example 128 The title compound was obtained as a pale-yellow oil by conducting the same operation as in Reference Example 19 using ethylamine.
MS m / z: 508 [M + H] ⁺

Reference Example 149

参考例１２９で得た5-クロロ-1-(1,3-ジメチル-2,2-ジオキシド-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール-5-イル)-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.41 (9H, s), 1.42-1.64 (4H, m), 2.97 (4H, m), 3.25 (2H, m), 3.34 (3H, s), 3.35 (3H, s), 3.45 (2H, m), 6.74 (1H, d, J = 8.4Hz), 7.18-7.39 (5H, m), 7.67 (1H, d, J = 8.4Hz). 2- (2-Chlorophenyl) ethyl [5- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -5-oxopentyl] carbamine Acid tert-butyl

5-Chloro-1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone obtained in Reference Example 129 and 2 The title compound was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using-(2-chlorophenyl) ethylamine.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.42-1.64 (4H, m), 2.97 (4H, m), 3.25 (2H, m), 3.34 (3H, s), 3.35 (3H , s), 3.45 (2H, m), 6.74 (1H, d, J = 8.4Hz), 7.18-7.39 (5H, m), 7.67 (1H, d, J = 8.4Hz).

Reference Example 150

参考例１４１で得た(±)-6-(3-クロロプロピル)-1,3-ジメチル-3,6,7,8-テトラヒドロ-1H-ナフト[2,3-d]イミダゾール-2,5-ジオンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.38 (9H, m), 1.42-1.61 (4H, m), 1.87 (2H, m), 2.23 (1H, m), 2.93-3.12 (4H, m), 3.19 (2H, m), 3.32 (2H, m), 3.34 (3H, s), 3.36 (3H, s), 6.72 (1H, s), 7.11-7.30 (4H, m), 7.60 (1H, s). (±) -2- (2-Chlorophenyl) ethyl [3- (1,3-dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-naphtho [2,3- d] imidazol-6-yl) propyl] carbamate tert-butyl

(±) -6- (3-Chloropropyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5 obtained in Reference Example 141 The title compound was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using -dione and 2- (2-chlorophenyl) ethylamine.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.38 (9H, m), 1.42-1.61 (4H, m), 1.87 (2H, m), 2.23 (1H, m), 2.93-3.12 (4H, m), 3.19 (2H, m), 3.32 (2H, m), 3.34 (3H, s), 3.36 (3H, s), 6.72 (1H, s), 7.11-7.30 (4H, m), 7.60 (1H, s).

Reference Example 151

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) およびトリプタミン(548mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(822mg) を淡黄色非晶状粉末として得た。
¹H NMR (300MHz, CDCl₃) δ 1.30-1.80 (13H, m), 2.70 (2H, t, J = 7.8Hz), 2.80-3.05 (6H, m), 3.10-3.35 (4H, m), 3.40-3.55 (2H, m), 4.12 (2H, t, J = 8.4Hz), 6.95-7.25 (3H, m), 7.36 (1H, d, J = 7.8Hz), 7.60-7.75 (3H, m), 8.10-8.30 (1H, br). 2- (1H-Indol-3-yl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8- Yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and tryptamine ( 548 mg) was used in the same manner as in Reference Example 19 to give the titled compound (822 mg) as a pale yellow amorphous powder.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.30-1.80 (13H, m), 2.70 (2H, t, J = 7.8Hz), 2.80-3.05 (6H, m), 3.10-3.35 (4H, m), 3.40 -3.55 (2H, m), 4.12 (2H, t, J = 8.4Hz), 6.95-7.25 (3H, m), 7.36 (1H, d, J = 7.8Hz), 7.60-7.75 (3H, m), 8.10-8.30 (1H, br).

Reference Example 152

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および(±)-2-アミノ-1-フェニルエタノール(470mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(1.29g) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.47 (9H, s), 1.50-1.90 (4H, m), 2.60-3.50 (13H, m), 4.00-4.20 (2H, m), 4.70-5.00 (1H, m), 7.10-7.45 (5H, m), 7.66 (1H, s), 7.70 (1H, s). (±) -2-Hydroxy-2-phenylethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8- Yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and (± ) -2-Amino-1-phenylethanol (470 mg) was used for the same operation as in Reference Example 19 to give the title compound (1.29 g) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.47 (9H, s), 1.50-1.90 (4H, m), 2.60-3.50 (13H, m), 4.00-4.20 (2H, m), 4.70-5.00 (1H, m), 7.10-7.45 (5H, m), 7.66 (1H, s), 7.70 (1H, s).

Reference Example 153

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および塩酸 (±)-ノルフェニレフリン(650mg) を用いて、参考例８２と同様の操作を行うことにより、表題化合物(201mg) を淡黄色非晶状粉末として得た。
¹H NMR (300MHz, CDCl₃) δ 1.40-1.80 (4H, m), 1.47 (9H, s), 2.71 (2H, t, J = 7.8Hz), 2.91 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.05-3.60 (7H, m), 4.13 (2H, t, J = 8.4Hz), 4.60-4.90 (1H, m), 6.35-6.60 (1H, br), 6.75 (1H, d, J = 8.5Hz), 6.80-6.90 (2H, m), 7.18 (1H, t, J = 7.8Hz), 7.66 (1H, s), 7.70 (1H, s). (±) -2-hydroxy-2- (3-hydroxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij ] Quinolin-8-yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and hydrochloric acid ( The title compound (201 mg) was obtained as a pale yellow amorphous powder by the same procedures as in Reference Example 82 using ±) -norphenylephrine (650 mg).
¹ H NMR (300MHz, CDCl ₃ ) δ 1.40-1.80 (4H, m), 1.47 (9H, s), 2.71 (2H, t, J = 7.8Hz), 2.91 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.05-3.60 (7H, m), 4.13 (2H, t, J = 8.4Hz), 4.60-4.90 (1H, m), 6.35-6.60 (1H, br) , 6.75 (1H, d, J = 8.5Hz), 6.80-6.90 (2H, m), 7.18 (1H, t, J = 7.8Hz), 7.66 (1H, s), 7.70 (1H, s).

Reference Example 154

1-メチル-3,4-ジヒドロ-2(1H)-キノリノン(1.3g) および5-クロロバレリルクロリド(1.49g) を用いて、参考例１と同様の操作を行うことにより、表題化合物を融点62-63℃の無色結晶(930mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.84-1.94 (4H, m), 2.69 (2H, t, J = 8Hz), 2.96-3.00 (4H, m), 3.39 (3H, s), 3.59 (2H, t, J = 6Hz), 7.04 (1H, d, J = 8.3Hz), 7.79 (1H, d, J = 1.5Hz), 7.88 (1H, dd, J = 8.3, 1.5Hz).
IR (KBr) νcm^-1: 1669, 1601, 1504, 1426, 1351, 1304, 1205, 1123. 6- (5-Chloropentanoyl) -1-methyl-3,4-dihydro-2 (1H) -quinolinone

The title compound was obtained by the same procedure as in Reference Example 1 using 1-methyl-3,4-dihydro-2 (1H) -quinolinone (1.3 g) and 5-chlorovaleryl chloride (1.49 g). Obtained as colorless crystals (930 mg) of melting point 62-63 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.84-1.94 (4H, m), 2.69 (2H, t, J = 8Hz), 2.96-3.00 (4H, m), 3.39 (3H, s), 3.59 (2H, t, J = 6Hz), 7.04 (1H, d, J = 8.3Hz), 7.79 (1H, d, J = 1.5Hz), 7.88 (1H, dd, J = 8.3, 1.5Hz).
IR (KBr) νcm ^-1 : 1669, 1601, 1504, 1426, 1351, 1304, 1205, 1123.

Reference Example 155

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オン(438mg) および2-(2-クロロ-4-フルオロフェニル)エチルアミン(573mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(452mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (9H, s), 1.51-1.75 (4H, m), 2.01-2.08 (2H, m), 2.82 (2H, t, J = 6Hz), 2.85-2.98 (4H, m), 3.13-3.21 (2H, m), 3.38 (2H, t, J = 7Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 6.91 (1H, dt, J = 2.7, 8.0Hz), 7.08-7.25 (2H, m), 7.72 (2H, s). 2- (2-Chloro-4-fluorophenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8 -Yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (438 mg) and 2- (2) obtained in Reference Example 3 The title compound (452 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using -chloro-4-fluorophenyl) ethylamine (573 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.51-1.75 (4H, m), 2.01-2.08 (2H, m), 2.82 (2H, t, J = 6Hz), 2.85-2.98 ( 4H, m), 3.13-3.21 (2H, m), 3.38 (2H, t, J = 7Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 6.91 (1H, dt, J = 2.7, 8.0Hz), 7.08-7.25 (2H, m), 7.72 (2H, s).

Reference Example 156

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(420mg) および2-(2-クロロ-4-フルオロフェニル)エチルアミン(573mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(554mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.25 (3H, s), 2.94 (4H, br.s,), 3.13-3.25 (4H, m), 3.38 (2H, t, J = 7Hz), 4.11 (2H, t, J = 7Hz), 6.91 (1H, dt, J = 2.5, 7.8Hz), 7.08-7.24 (2H, m), 7.80 (1H, s), 7.81 (1H, d, J = 8.0Hz), 8.23 (1H, d, J = 8.0Hz). 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-chloro-4-fluorophenyl) ethyl] carbamate tert-butyl

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (420 mg) and 2- (2-chloro-4-fluoro) obtained in Reference Example 11 The title compound (554 mg) was obtained as a pale yellow oil by the same operation as in Reference Example 19 using phenyl) ethylamine (573 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.25 (3H, s), 2.94 (4H, br.s,), 3.13-3.25 (4H, m ), 3.38 (2H, t, J = 7Hz), 4.11 (2H, t, J = 7Hz), 6.91 (1H, dt, J = 2.5, 7.8Hz), 7.08-7.24 (2H, m), 7.80 (1H , s), 7.81 (1H, d, J = 8.0Hz), 8.23 (1H, d, J = 8.0Hz).

Reference Example 157

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン(420mg) および2-(2-クロロ-4-フルオロフェニル)エチルアミン(573mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(472mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7.0Hz), 2.95-2.99 (6H, m), 3.13-3.21 (2H, m), 3.36-3.40 (2H, m), 3.39 (3H, s), 6.91 (1H, dt, J = 2.5, 8.3Hz), 7.02 (1H, d, J = 8.3Hz), 7.09-7.22 (2H, m), 7.78 (1H, s), 7.87 (1H, d, J = 8.3Hz). 2- (2-Chloro-4-fluorophenyl) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl] carbamic acid tert- Butyl

6- (5-Chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (420 mg) and 2- (2-chloro-4-fluorophenyl) ethylamine obtained in Reference Example 154 (573 mg) was used in the same manner as in Reference Example 19 to give the titled compound (472 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7.0Hz), 2.95-2.99 (6H, m), 3.13-3.21 (2H, m), 3.36-3.40 (2H, m), 3.39 (3H, s), 6.91 (1H, dt, J = 2.5, 8.3Hz), 7.02 (1H, d, J = 8.3Hz), 7.09- 7.22 (2H, m), 7.78 (1H, s), 7.87 (1H, d, J = 8.3Hz).

Reference Example 158

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オン(292mg) および2-[2-(トリフルオロメトキシ)フェニル]エチルアミン(451mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(205mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (9H, s), 1.51-1.72 (4H, m), 2.02-2.34 (2H, m), 2.80-2.90 (6H, m), 3.13-3.20 (2H, m), 3.38 (2H, br.s), 3.54 (2H, s), 3.72-3.75 (2H, m), 7.22 (4H, br.s), 7.72 (2H, s). 5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl {2- [2- (trifluoromethoxy ) Phenyl] ethyl} carbamate tert-butyl

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (292 mg) and 2- [2 obtained in Reference Example 3 The title compound (205 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using-(trifluoromethoxy) phenyl] ethylamine (451 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.51-1.72 (4H, m), 2.02-2.34 (2H, m), 2.80-2.90 (6H, m), 3.13-3.20 (2H, m), 3.38 (2H, br.s), 3.54 (2H, s), 3.72-3.75 (2H, m), 7.22 (4H, br.s), 7.72 (2H, s).

Reference Example 159

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(280mg) および2-[2-(トリフルオロメトキシ)フェニル]エチルアミン(451mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(457mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (9H, s), 1.51-1.69 (4H, m), 2.25 (3H, s), 2.92-2.99 (4H, m), 3.12-3.25 (4H, m), 3.38 (2H, br.s), 4.09-4.15 (2H, m), 7.19-7.32 (4H, m), 7.80 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.23 (1H, d, J = 8.3Hz). 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl {2- [2- (trifluoromethoxy) phenyl] ethyl} carbamate tert-butyl

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (280 mg) and 2- [2- (trifluoromethoxy) obtained in Reference Example 11 The same operation as in Reference Example 19 was carried out using phenyl] ethylamine (451 mg) to give the title compound (457 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.51-1.69 (4H, m), 2.25 (3H, s), 2.92-2.99 (4H, m), 3.12-3.25 (4H, m) , 3.38 (2H, br.s), 4.09-4.15 (2H, m), 7.19-7.32 (4H, m), 7.80 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.23 (1H , d, J = 8.3Hz).

Reference Example 160

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン(280mg) および2-[2-(トリフルオロメトキシ)フェニル]エチルアミン(451mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(442mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7.7Hz), 2.88-3.00 (6H, m), 3.14-3.21 (2H, m), 3.35-3.42 (2H, m), 3.39 (3H, s), 7.02 (1H, d, J =8.3Hz), 7.09-7.22 (2H, m), 7.78 (1H, s), 7.87 (1H, d, J =8.3Hz). 5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl {2- [2- (trifluoromethoxy) phenyl] ethyl} carbamic acid tert- Butyl

6- (5-Chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (280 mg) and 2- [2- (trifluoromethoxy) phenyl] ethylamine obtained in Reference Example 154 (451 mg) was used in the same manner as in Reference Example 19 to give the titled compound (442 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7.7Hz), 2.88-3.00 (6H, m), 3.14-3.21 (2H, m), 3.35-3.42 (2H, m), 3.39 (3H, s), 7.02 (1H, d, J = 8.3Hz), 7.09-7.22 (2H, m), 7.78 (1H, s), 7.87 (1H, d, J = 8.3Hz).

Reference Example 161

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(281mg) および2-[2-(トリフルオロメトキシ)フェニル]エチルアミン(451mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(244mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (9H, s), 1.51-1.78 (4H, m), 2.89 (2H, br.s), 3.01 (2H, br.s), 3.15-3.23 (2H, m), 3.38 (2H, br.s), 3.46 (6H, s), 6.98 (1H, d, J = 8.0Hz), 7.23-7.30 (4H, m), 7.63 (1H, s), 7.78 (1H, d, J = 8.0Hz). 5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl {2- [2- (trifluoromethoxy) phenyl] ethyl} carbamic acid tert-butyl

5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one (281 mg) and 2- [2- (trifluoromethoxy) obtained in Reference Example 10 The same operation as in Reference Example 19 was carried out using phenyl] ethylamine (451 mg) to give the title compound (244 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.51-1.78 (4H, m), 2.89 (2H, br.s), 3.01 (2H, br.s), 3.15-3.23 (2H, m), 3.38 (2H, br.s), 3.46 (6H, s), 6.98 (1H, d, J = 8.0Hz), 7.23-7.30 (4H, m), 7.63 (1H, s), 7.78 (1H , d, J = 8.0Hz).

Reference Example 162

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オン(292mg) および3-(2-メトキシフェニル)プロピルアミン(364mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(165mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (9H, s), 1.60 (2H, br.s), 1.67-1.74 (2H, m), 1.76-1.84 (2H, m), 2.00-2.06 (2H, m), 2.58 (2H, t, J = 7.5Hz), 2.82 (2H, t, J = 6.0Hz), 2.94 (2H, t, J = 7.0Hz), 3.22 (4H, br.s), 3.54 (2H, s), 3.74 (2H, t, J = 6.0Hz), 3.81 (3H, s), 6.84 (1H, d, J = 8.3Hz), 6.87 (1H, t, J = 7.5Hz), 7.12 (1H, d, J = 7.5Hz), 7.17 (1H, t, J = 7.5Hz), 7.73 (2H, s). 3- (2-Methoxyphenyl) propyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (292 mg) and 3- (2) obtained in Reference Example 3 The title compound (165 mg) was obtained as a pale yellow oil by the same procedure as in Reference Example 19 using -methoxyphenyl) propylamine (364 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.60 (2H, br.s), 1.67-1.74 (2H, m), 1.76-1.84 (2H, m), 2.00-2.06 (2H, m), 2.58 (2H, t, J = 7.5Hz), 2.82 (2H, t, J = 6.0Hz), 2.94 (2H, t, J = 7.0Hz), 3.22 (4H, br.s), 3.54 ( 2H, s), 3.74 (2H, t, J = 6.0Hz), 3.81 (3H, s), 6.84 (1H, d, J = 8.3Hz), 6.87 (1H, t, J = 7.5Hz), 7.12 ( 1H, d, J = 7.5Hz), 7.17 (1H, t, J = 7.5Hz), 7.73 (2H, s).

Reference Example 163

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(280mg) および3-(2-メトキシフェニル)プロピルアミン(364mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(417mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.44 (9H, s), 1.60 (2H, br.s), 1.67-1.72 (2H, m), 1.76-1.84 (2H, m), 2.25 (3H, s), 2.58 (2H, t, J = 7.3Hz), 2.93-2.96 (2H, m), 3.23 (6H, br.s), 3.81 (3H, s), 4.09-4.15 (2H, m), 6.83 (1H, d, J = 8.3Hz), 6.87 (1H, t, J = 7.3Hz), 7.12 (1H, d, J = 7.3Hz), 7.17 (1H, t, J = 7.3Hz), 7.81 (1H, s), 7.82 (1H, d, J = 8.1Hz), 8.23 (1H, d, J = 8.1Hz). Tert-Butyl 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [3- (2-methoxyphenyl) propyl] carbamate

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (280 mg) and 3- (2-methoxyphenyl) propylamine obtained in Reference Example 11 (364 mg) was used for the same operation as in Reference Example 19 to give the title compound (417 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.60 (2H, br.s), 1.67-1.72 (2H, m), 1.76-1.84 (2H, m), 2.25 (3H, s) , 2.58 (2H, t, J = 7.3Hz), 2.93-2.96 (2H, m), 3.23 (6H, br.s), 3.81 (3H, s), 4.09-4.15 (2H, m), 6.83 (1H , d, J = 8.3Hz), 6.87 (1H, t, J = 7.3Hz), 7.12 (1H, d, J = 7.3Hz), 7.17 (1H, t, J = 7.3Hz), 7.81 (1H, s ), 7.82 (1H, d, J = 8.1Hz), 8.23 (1H, d, J = 8.1Hz).

Reference Example 164

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン(280mg) および3-(2-メトキシフェニル)プロピルアミン(364mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(415mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.44 (9H, s), 1.61 (2H, br.s), 1.68-1.75 (2H, m), 1.77-1.84 (2H, m), 2.58 (2H, t, J = 7.8Hz), 2.68 (2H, t, J = 7.8Hz), 2.95-2.98 (4H, m), 3.21 (4H, br.s), 3.39 (3H, s), 3.81 (3H, s), 6.84 (1H, d, J = 8.0Hz), 6.88 (1H, t, J = 7.3Hz), 7.01 (1H, d, J = 8.3Hz), 7.12 (1H, d, J = 7.3Hz), 7.17 (1H, t, J = 7.3Hz), 7.79 (1H, s), 7.87 (1H, d, J = 8.3Hz). 3- (2-methoxyphenyl) propyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl] carbamic acid tert-butyl

6- (5-Chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (280 mg) and 3- (2-methoxyphenyl) propylamine (364 mg) obtained in Reference Example 154 Was used for the same operation as in Reference Example 19 to give the title compound (415 mg) as a pale-yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.61 (2H, br.s), 1.68-1.75 (2H, m), 1.77-1.84 (2H, m), 2.58 (2H, t, J = 7.8Hz), 2.68 (2H, t, J = 7.8Hz), 2.95-2.98 (4H, m), 3.21 (4H, br.s), 3.39 (3H, s), 3.81 (3H, s), 6.84 (1H, d, J = 8.0Hz), 6.88 (1H, t, J = 7.3Hz), 7.01 (1H, d, J = 8.3Hz), 7.12 (1H, d, J = 7.3Hz), 7.17 ( 1H, t, J = 7.3Hz), 7.79 (1H, s), 7.87 (1H, d, J = 8.3Hz).

Reference Example 165

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(281mg) および3-(2-メトキシフェニル)プロピルアミン(364mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(387mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.44 (9H, s), 1.63 (2H, br.s), 1.70-1.85 (4H, m), 2.58 (2H, t, J = 7.8Hz), 3.01 (2H, t, J = 7.0Hz), 3.25 (4H, br.s), 3.46 (6H, s), 3.81 (3H, s), 6.84 (1H, d, J = 8.0Hz), 6.87 (1H, t, J = 7.3Hz), 6.98 (1H, d, J = 8.0Hz), 7.12 (1H, d, J = 7.3Hz), 7.17 (1H, t, J = 7.3Hz), 7.63 (1H, s), 7.78 (1H, d, J = 8.0Hz). 5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl [3- (2-methoxyphenyl) propyl] carbamate tert-butyl

5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one (281 mg) and 3- (2-methoxyphenyl) propylamine obtained in Reference Example 10 (364 mg) was used for the same operation as in Reference Example 19 to give the title compound (387 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.63 (2H, br.s), 1.70-1.85 (4H, m), 2.58 (2H, t, J = 7.8Hz), 3.01 (2H , t, J = 7.0Hz), 3.25 (4H, br.s), 3.46 (6H, s), 3.81 (3H, s), 6.84 (1H, d, J = 8.0Hz), 6.87 (1H, t, J = 7.3Hz), 6.98 (1H, d, J = 8.0Hz), 7.12 (1H, d, J = 7.3Hz), 7.17 (1H, t, J = 7.3Hz), 7.63 (1H, s), 7.78 (1H, d, J = 8.0Hz).

Reference Example 166

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オン(292mg) および2-(2-エトキシフェノキシ)エチルアミン(399mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(211mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (3H, t, J = 7Hz), 1.45 (9H, s), 1.61-1.75 (4H, m), 2.00-2.06 (2H, m), 2.81 (2H, t, J = 6Hz), 2.94 (2H, br.d, J = 6.6Hz), 3.42 (2H, t, J = 7.3Hz), 3.54 (2H, s), 3.59-3.63 (2H, m), 3.74 (2H, t, J = 6Hz), 4.03-4.08 (2H, m), 4.12 (2H, q, J = 7Hz), 6.89 (4H, br.s), 7.73 (2H, s). 2- (2-Ethoxyphenoxy) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl ] Tert-butyl carbamate

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (292 mg) and 2- (2) obtained in Reference Example 3 The title compound (211 mg) was obtained as a pale yellow oil by the same procedures as in Reference Example 19 using -ethoxyphenoxy) ethylamine (399 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (3H, t, J = 7Hz), 1.45 (9H, s), 1.61-1.75 (4H, m), 2.00-2.06 (2H, m), 2.81 (2H, t, J = 6Hz), 2.94 (2H, br.d, J = 6.6Hz), 3.42 (2H, t, J = 7.3Hz), 3.54 (2H, s), 3.59-3.63 (2H, m), 3.74 (2H, t, J = 6Hz), 4.03-4.08 (2H, m), 4.12 (2H, q, J = 7Hz), 6.89 (4H, br.s), 7.73 (2H, s).

Reference Example 167

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(280mg) および2-(2-エトキシフェノキシ)エチルアミン(399mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(398mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (3H, t, J = 7Hz), 1.45 (9H, s), 1.61-1.72 (4H, m), 2.25 (3H, s), 2.95-2.97 (2H, m), 3.22 (2H, t, J = 8Hz), 3.42 (2H, t, J = 7Hz), 3.58-3.68 (2H, m), 4.03-4.06 (2H, m), 4.11 (4H, q, J = 7Hz), 6.89 (4H, br.s), 7.79 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.22 (1H, d, J = 8.3Hz). 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-ethoxyphenoxy) ethyl] carbamate tert-butyl

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (280 mg) and 2- (2-ethoxyphenoxy) ethylamine (280 mg) obtained in Reference Example 11 399 mg) was used in the same manner as in Reference Example 19 to give the title compound (398 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (3H, t, J = 7Hz), 1.45 (9H, s), 1.61-1.72 (4H, m), 2.25 (3H, s), 2.95-2.97 (2H, m), 3.22 (2H, t, J = 8Hz), 3.42 (2H, t, J = 7Hz), 3.58-3.68 (2H, m), 4.03-4.06 (2H, m), 4.11 (4H, q, J = 7Hz), 6.89 (4H, br.s), 7.79 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.22 (1H, d, J = 8.3Hz).

Reference Example 168

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン(280mg) および2-(2-エトキシフェノキシ)エチルアミン(399mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(425mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (3H, t, J = 7Hz), 1.45 (9H, s), 1.70-1.76 (4H, m), 2.68 (2H, t, J = 8.3Hz), 2.94-2.98 (4H, m), 3.39 (3H, s), 3.43 (2H, t, J = 7.3Hz), 3.59-3.64 (2H, m), 4.03-4.08 (2H, m), 4.12 (2H, q, J = 7Hz), 6.89 (4H, br.s), 7.01 (1H, d, J = 8.3Hz), 7.78 (1H, s), 7.88 (1H, d, J = 8.3Hz). 2- (2-Ethoxyphenoxy) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl] carbamate tert-butyl

6- (5-Chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (280 mg) and 2- (2-ethoxyphenoxy) ethylamine (399 mg) obtained in Reference Example 154 were used. Using the same procedure as in Reference Example 19, the title compound (425 mg) was obtained as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (3H, t, J = 7Hz), 1.45 (9H, s), 1.70-1.76 (4H, m), 2.68 (2H, t, J = 8.3Hz), 2.94 -2.98 (4H, m), 3.39 (3H, s), 3.43 (2H, t, J = 7.3Hz), 3.59-3.64 (2H, m), 4.03-4.08 (2H, m), 4.12 (2H, q , J = 7Hz), 6.89 (4H, br.s), 7.01 (1H, d, J = 8.3Hz), 7.78 (1H, s), 7.88 (1H, d, J = 8.3Hz).

Reference Example 169

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(281mg) および2-(2-エトキシフェノキシ)エチルアミン(399mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(368mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (3H, t, J = 6.7Hz), 1.45 (9H, s), 1.70-1.78 (4H, m), 3.01-3.06 (2H, m), 3.42-3.46 (2H, m), 3.46 (6H, s), 3.59-3.64 (2H, m), 4.05 (2H, q, J = 6.7Hz), 4.10-4.15 (2H, m), 6.89 (4H, br.s), 6.97 (1H, d, J = 8Hz), 7.63 (1H, s), 7.78 (1H, d, J = 8Hz). 5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl [2- (2-ethoxyphenoxy) ethyl] carbamate tert-butyl

5- (5-chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzoimidazol-2-one (281 mg) and 2- (2-ethoxyphenoxy) ethylamine (281 mg) obtained in Reference Example 10 399 mg) was used in the same manner as in Reference Example 19 to give the title compound (368 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (3H, t, J = 6.7Hz), 1.45 (9H, s), 1.70-1.78 (4H, m), 3.01-3.06 (2H, m), 3.42-3.46 (2H, m), 3.46 (6H, s), 3.59-3.64 (2H, m), 4.05 (2H, q, J = 6.7Hz), 4.10-4.15 (2H, m), 6.89 (4H, br.s ), 6.97 (1H, d, J = 8Hz), 7.63 (1H, s), 7.78 (1H, d, J = 8Hz).

Reference Example 170

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オン(584mg) およびN-(2-エトキシフェニル)エタン-1,2-ジアミン(793mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(611mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (3H, t, J = 7.0Hz), 1.47 (9H, s), 1.63 (1H, br.s), 1.66-1.75 (4H, m), 2.00-2.06 (2H, m), 2.82 (2H, t, J = 6.1Hz), 2.92-2.98 (2H, m), 3.23-3.33 (4H, m), 3.44 (2H, br.s), 3.54 (2H, s), 3.74 (2H, t, J = 6.1Hz), 4.05 (2H, br.s), 6.63 (2H, br.s), 6.74 (1H, d, J = 7.6Hz), 6.84 (1H, t, J = 7.6Hz), 7.72 (1H, s), 7.73 (1H, s). 2-[(2-Ethoxyphenyl) amino] ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8- Yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (584 mg) and N- (2) obtained in Reference Example 3 The title compound (611 mg) was obtained as a pale yellow oil by the same procedure as in Reference Example 19 using -ethoxyphenyl) ethane-1,2-diamine (793 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (3H, t, J = 7.0Hz), 1.47 (9H, s), 1.63 (1H, br.s), 1.66-1.75 (4H, m), 2.00-2.06 (2H, m), 2.82 (2H, t, J = 6.1Hz), 2.92-2.98 (2H, m), 3.23-3.33 (4H, m), 3.44 (2H, br.s), 3.54 (2H, s ), 3.74 (2H, t, J = 6.1Hz), 4.05 (2H, br.s), 6.63 (2H, br.s), 6.74 (1H, d, J = 7.6Hz), 6.84 (1H, t, J = 7.6Hz), 7.72 (1H, s), 7.73 (1H, s).

Reference Example 171

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(560mg) およびN-(2-エトキシフェニル)エタン-1,2-ジアミン(793mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(695mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (3H, t, J = 6.8Hz), 1.47 (9H, s), 1.62 (1H, br.s), 1.67-1.74 (4H, m), 2.26 (3H, s), 2.93-2.97 (2H, m), 3.21-3.25 (4H, m), 3.31 (2H, t, J = 6.8Hz), 3.43 (2H, br.s), 4.04 (2H, br.s), 4.12 (2H, q, J = 6.8Hz), 6.63 (2H, br.s), 6.74 (1H, d, J = 7.6Hz), 6.84 (1H, t, J = 7.6Hz), 7.80 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.23 (1H, d, J = 8.3Hz). 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl {2-[(2-ethoxyphenyl) amino] ethyl} carbamate tert-butyl

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (560 mg) and N- (2-ethoxyphenyl) ethane- obtained in Reference Example 11 The same operation as in Reference Example 19 was carried out using 1,2-diamine (793 mg) to give the title compound (695 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (3H, t, J = 6.8Hz), 1.47 (9H, s), 1.62 (1H, br.s), 1.67-1.74 (4H, m), 2.26 (3H , s), 2.93-2.97 (2H, m), 3.21-3.25 (4H, m), 3.31 (2H, t, J = 6.8Hz), 3.43 (2H, br.s), 4.04 (2H, br.s ), 4.12 (2H, q, J = 6.8Hz), 6.63 (2H, br.s), 6.74 (1H, d, J = 7.6Hz), 6.84 (1H, t, J = 7.6Hz), 7.80 (1H , s), 7.82 (1H, d, J = 8.3Hz), 8.23 (1H, d, J = 8.3Hz).

Reference Example 172

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(562mg) およびN-(2-エトキシフェニル)エタン-1,2-ジアミン(793mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(670mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.42 (3H, t, J = 6.8Hz), 1.47 (9H, s), 1.63 (1H, br.s), 1.71-1.80 (4H, m), 3.00-3.05 (2H, m), 3.27-3.33 (4H, m), 3.42-3.49 (2H, m), 3.46 (6H, s), 4.04 (2H, br.s), 6.63 (2H, br.s), 6.74 (1H, d, J = 7.3Hz), 6.84 (1H, t, J = 7.3Hz), 6.98 (1H, d, J = 8.0Hz), 7.62 (1H, s), 7.78 (1H, d, J = 8.0Hz). 5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl {2-[(2-ethoxyphenyl) amino] ethyl} carbamic acid tert -Butyl

5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one (562 mg) and N- (2-ethoxyphenyl) ethane- obtained in Reference Example 10 The same operation as in Reference Example 19 was carried out using 1,2-diamine (793 mg) to give the title compound (670 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.42 (3H, t, J = 6.8Hz), 1.47 (9H, s), 1.63 (1H, br.s), 1.71-1.80 (4H, m), 3.00-3.05 (2H, m), 3.27-3.33 (4H, m), 3.42-3.49 (2H, m), 3.46 (6H, s), 4.04 (2H, br.s), 6.63 (2H, br.s), 6.74 (1H, d, J = 7.3Hz), 6.84 (1H, t, J = 7.3Hz), 6.98 (1H, d, J = 8.0Hz), 7.62 (1H, s), 7.78 (1H, d, J = 8.0Hz).

Reference Example 173

3-(1-アセチル-4-ピペリジニル)プロパン酸13.8gジクロロメタン(50ml) 懸濁液に塩化チオニル(5.6ml) を氷冷下滴下した。同温下30分間攪拌後、減圧濃縮し残渣にヘキサン30mlを加え晶出した結晶をろ取し乾燥した。得られた対応する酸クロリドおよび5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(10g)の1,2-ジクロロエタン(50ml) 懸濁液に、水冷下、塩化アルミニウム(28g) を少量ずつ加えた。室温で３０分攪拌後、反応溶液を氷(200g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、エタノール−ジエチルエーテルから結晶化することにより、表題化合物を融点119-120℃の淡黄色結晶(8.0g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.08-1.24 (2H, m), 1.55-1.81 (5H, m), 2.00-2.10 (2H, m), 2.09 (3H, s), 2.53 (1H, d, t, J = 2.5, 13Hz), 2.83 (2H, t, J = 6.7Hz), 2.95 (2H, t, J = 7.5Hz), 3.03 (1H, d, t, J = 2.5, 13Hz), 3.56 (2H, s), 3.75 (2H, t, J = 6.7Hz), 3.80 (1H, d, J = 7.5Hz), 4.61 (1H, d, J = 7.5Hz), 7.73 (2H, s).
IR (KBr) νcm^-1: 1713, 1634, 1341, 1152. 8- [3- (1-Acetyl-4-piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one

Thionyl chloride (5.6 ml) was added dropwise to a suspension of 3- (1-acetyl-4-piperidinyl) propanoic acid 13.8 g dichloromethane (50 ml) under ice cooling. After stirring for 30 minutes at the same temperature, the mixture was concentrated under reduced pressure, 30 ml of hexane was added to the residue, and the crystallized crystals were collected by filtration and dried. To a suspension of the corresponding acid chloride obtained and 5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (10 g) in 1,2-dichloroethane (50 ml) Under cooling with water, aluminum chloride (28 g) was added in small portions. After stirring at room temperature for 30 minutes, the reaction solution was poured into ice (200 g), extracted with ethyl acetate, and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure and crystallized from ethanol-diethyl ether to obtain the title compound as pale yellow crystals (8.0 g) having a melting point of 119-120 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.08-1.24 (2H, m), 1.55-1.81 (5H, m), 2.00-2.10 (2H, m), 2.09 (3H, s), 2.53 (1H, d, t, J = 2.5, 13Hz), 2.83 (2H, t, J = 6.7Hz), 2.95 (2H, t, J = 7.5Hz), 3.03 (1H, d, t, J = 2.5, 13Hz), 3.56 ( 2H, s), 3.75 (2H, t, J = 6.7Hz), 3.80 (1H, d, J = 7.5Hz), 4.61 (1H, d, J = 7.5Hz), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1713, 1634, 1341, 1152.

Reference Example 174

参考例１７３で得た8-[3-(1-アセチル-4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(7.5g) に濃塩酸(150ml) を加え、120℃で５時間攪拌した。塩酸を減圧下留去した後、１規定水酸化ナトリウム水溶液でpH=12 とし、酢酸エチル(100ml) で３回抽出した。有機層を無水硫酸マグネシウムで乾燥した後、溶媒を留去することにより、表題化合物を融点128-129℃の淡黄色結晶(3.48g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.14 (1H, d, t, J = 4, 12Hz), 1.17 (1H, d, t, J = 4, 12Hz), 1.42-1.46 (1H, m), 1.65-1.81 (5H, m), 2.04 (2H, t, J = 7Hz), 2.58 (2H, d, t, J = 2, 12Hz), 2.83 (2H, t, J = 6Hz), 2.94 (2H, t, J = 7Hz), 3.07 (2H, br, d, J = 12Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.73 (2H, s).
IR (KBr) νcm^-1: 1708, 1660, 1603, 1339, 1156. 8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one

8- [3- (1-Acetyl-4-piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 173 ( Concentrated hydrochloric acid (150 ml) was added to 7.5 g) and stirred at 120 ° C. for 5 hours. Hydrochloric acid was distilled off under reduced pressure, adjusted to pH = 12 with 1N aqueous sodium hydroxide solution, and extracted three times with ethyl acetate (100 ml). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated to obtain the title compound as pale yellow crystals (3.48 g) having a melting point of 128-129 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.14 (1H, d, t, J = 4, 12Hz), 1.17 (1H, d, t, J = 4, 12Hz), 1.42-1.46 (1H, m), 1.65 -1.81 (5H, m), 2.04 (2H, t, J = 7Hz), 2.58 (2H, d, t, J = 2, 12Hz), 2.83 (2H, t, J = 6Hz), 2.94 (2H, t , J = 7Hz), 3.07 (2H, br, d, J = 12Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1708, 1660, 1603, 1339, 1156.

Reference Example 175

3-(1-アセチル-4-ピペリジニル)プロパン酸(13.8g) および2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン(10.8g) を用いて、参考例１７２と同様の操作を行うことにより、表題化合物を融点130-131℃の無色結晶(15.5g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.09-1.28 (2H, m), 1.55-1.82 (5H, m), 1.93-2.00 (2H, m), 2.09 (3H, s), 2.53 (1H, d, t, J = 2.5, 12.7Hz), 2.68 (2H, t, J = 7Hz), 2.85 (2H, t, J = 6Hz), 2.93-2.98 (4H, m), 3.03 (1H, d, t, J = 2.5, 12.7Hz), 3.82 (1H, d, J = 12.7Hz ), 3.90 (2H, t, J = 6Hz), 4.61 (1H, d, J = 13Hz), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1671, 1634, 1360, 1160, 972. 9- [3- (1-Acetyl-4-piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one

3- (1-acetyl-4-piperidinyl) propanoic acid (13.8 g) and 2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one (10.8 g ) To give the title compound as colorless crystals (15.5 g) having a melting point of 130-131 ° C. by the same procedure as in Reference Example 172.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.09-1.28 (2H, m), 1.55-1.82 (5H, m), 1.93-2.00 (2H, m), 2.09 (3H, s), 2.53 (1H, d, t, J = 2.5, 12.7Hz), 2.68 (2H, t, J = 7Hz), 2.85 (2H, t, J = 6Hz), 2.93-2.98 (4H, m), 3.03 (1H, d, t, J = 2.5, 12.7Hz), 3.82 (1H, d, J = 12.7Hz), 3.90 (2H, t, J = 6Hz), 4.61 (1H, d, J = 13Hz), 7.62 (2H, d, J = 5Hz ).
IR (KBr) νcm ^-1 : 1671, 1634, 1360, 1160, 972.

Reference Example 176

参考例１７５で得た9-[3-(1-アセチル-4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン(15g) を用いて、参考例１７３と同様の操作を行うことにより、表題化合物を融点81-82℃の淡黄色結晶(8.9g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.14 (1H, d, t, J = 4, 12Hz), 1.17 (1H, d, t, J = 4, 12Hz), 1.41-1.48 (1H, m), 1.65-1.70 (4H, m), 1.73 (1H, br. s), 1.94-2.00 (2H, m), 2.58 (2H, d, t, J = 2, 12Hz), 2.68 (2H, t, J = 6.7Hz), 2.84 (2H, t, J = 6Hz), 2.92-2.96 (4H,m), 3.07 (2H, br, d, J = 12Hz), 3.89 (2H, t, J = 6Hz),7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 3442, 2905, 1673, 1588, 1361, 1164. 9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one

9- [3- (1-Acetyl-4-piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5 obtained in Reference Example 175 The title compound was obtained as pale-yellow crystals (8.9 g) with a melting point of 81-82 ° C. by conducting the same operation as in Reference Example 173 using -one (15 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.14 (1H, d, t, J = 4, 12Hz), 1.17 (1H, d, t, J = 4, 12Hz), 1.41-1.48 (1H, m), 1.65 -1.70 (4H, m), 1.73 (1H, br.s), 1.94-2.00 (2H, m), 2.58 (2H, d, t, J = 2, 12Hz), 2.68 (2H, t, J = 6.7 Hz), 2.84 (2H, t, J = 6Hz), 2.92-2.96 (4H, m), 3.07 (2H, br, d, J = 12Hz), 3.89 (2H, t, J = 6Hz), 7.62 (2H , d, J = 5Hz).
IR (KBr) νcm ^-1 : 3442, 2905, 1673, 1588, 1361, 1164.

Reference Example 177

3,4-ジヒドロ-2(1H)-キナゾリノン(4.0g) および5-クロロバレリルクロリド(8.37g) を用いて、参考例１と同様の操作を行うことにより、表題化合物を無色結晶 (3.9g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.73 (4H, m), 2.96 (2H, t, J = 7.0 Hz), 3.67 (2H, t, J = 6.4 Hz), 4.38 (2H, s), 6.83 (1H, d, J = 8.8 Hz), 7.01 (1H, s), 7.75-7.80 (2H, m), 9.44 (1H, s).
元素分析 C₁₃H₁₅ClN₂O₂として
計算値：C, 58.54; H, 5.67; N, 10.50.
実験値：C, 58.47; H, 5.51; N, 10.39.
MS m/z: 267 [M+H]⁺ 6- (5-Chloropentanoyl) -3,4-dihydro-2 (1H) -quinazolinone

The title compound was obtained in the same manner as in Reference Example 1 by using 3,4-dihydro-2 (1H) -quinazolinone (4.0 g) and 5-chlorovaleryl chloride (8.37 g) to give colorless crystals (3.9 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.73 (4H, m), 2.96 (2H, t, J = 7.0 Hz), 3.67 (2H, t, J = 6.4 Hz), 4.38 (2H, s), 6.83 (1H, d, J = 8.8 Hz), 7.01 (1H, s), 7.75-7.80 (2H, m), 9.44 (1H, s).
Elemental analysis Calculated as C ₁₃ H ₁₅ ClN ₂ O ₂ : C, 58.54; H, 5.67; N, 10.50.
Experimental value: C, 58.47; H, 5.51; N, 10.39.
MS m / z: 267 [M + H] ⁺

Reference Example 178

1,3-ジメチル-3,4-ジヒドロ-2(1H)-キナゾリノン(4.0g) および5-クロロバレリルクロリド(6.46g) を用いて、参考例１と同様の操作を行うことにより、表題化合物を無色結晶 (3.5g)として得た。
1H NMR (300MHz, CDCl₃) δ 1.91-1.87 (4H, m), 2.99-2.94 (2H,m), 3.06 (3H, s) 3.35 (3H, s), 3.61-3.57 (2H, m), 4.43 (2H, s), 6.87 (1H, d, J = 8.4Hz), 7.07 (1H, d, J = 2.1Hz), 7.88 (1H, d, J = 8.4, 2.1Hz). 6- (5-Chloropentanoyl) -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone

By performing the same operation as in Reference Example 1 using 1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone (4.0 g) and 5-chlorovaleryl chloride (6.46 g), the title was obtained. The compound was obtained as colorless crystals (3.5 g).
1H NMR (300MHz, CDCl ₃ ) δ 1.91-1.87 (4H, m), 2.99-2.94 (2H, m), 3.06 (3H, s) 3.35 (3H, s), 3.61-3.57 (2H, m), 4.43 (2H, s), 6.87 (1H, d, J = 8.4Hz), 7.07 (1H, d, J = 2.1Hz), 7.88 (1H, d, J = 8.4, 2.1Hz).

Reference Example 179

1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(20.0g) および5-クロロバレリルクロリド(17.8ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物 (23.0g) を融点123-124℃の無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 2.23 (2H, quintet, J = 6.4Hz), 2.72 (2H, t, J = 7.6Hz), 3.04 (2H, t, J = 7.6Hz), 3.13 (2H, t, J = 6.4Hz), 3.24 (2H, t, J = 8.6Hz), 3.68 (2H, t, J = 6.4Hz), 4.14 (2H, t, J = 8.6Hz), 7.70 (1H, s), 7.75 (1H, s).
元素分析 C₁₅H₁₆ClNO₂ として
計算値：C, 64.87; H, 5.81; N, 5.04.
実験値：C, 64.88; H, 5.72; N, 4.91. 8- (4-Chlorobutanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one

Using 1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (20.0 g) and 5-chlorovaleryl chloride (17.8 ml), The title compound (23.0 g) was obtained as colorless crystals having a melting point of 123-124 ° C. by carrying out the same operation.
¹ H NMR (200MHz, CDCl ₃ ) δ 2.23 (2H, quintet, J = 6.4Hz), 2.72 (2H, t, J = 7.6Hz), 3.04 (2H, t, J = 7.6Hz), 3.13 (2H, t, J = 6.4Hz), 3.24 (2H, t, J = 8.6Hz), 3.68 (2H, t, J = 6.4Hz), 4.14 (2H, t, J = 8.6Hz), 7.70 (1H, s) , 7.75 (1H, s).
Elemental analysis Calculated as C ₁₅ H ₁₆ ClNO ₂ : C, 64.87; H, 5.81; N, 5.04.
Experimental value: C, 64.88; H, 5.72; N, 4.91.

Reference Example 180

参考例１７９で得た8-(4-クロロブタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) およびベンジルアミン(1.16g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(526mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.44 (9H, s), 1.80-2.05 (2H, m), 2.71 (2H, t, J = 7.6Hz), 2.80-2.95 (2H, m), 3.11 (2H, t, J = 7.6Hz), 3.15-3.40 (4H, m), 4.13 (2H, t, J = 8.8Hz), 4.45 (2H, s), 7.20-7.40 (5H, m), 7.64 (1H, s), 7.68 (1H, s). Benzyl [4-oxo-4- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) butyl] carbamate tert-butyl

8- (4-Chlorobutanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) and benzylamine obtained in Reference Example 179 (1.16 g) was used for the same operation as in Reference Example 19 to give the titled compound (526 mg) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.80-2.05 (2H, m), 2.71 (2H, t, J = 7.6Hz), 2.80-2.95 (2H, m), 3.11 (2H , t, J = 7.6Hz), 3.15-3.40 (4H, m), 4.13 (2H, t, J = 8.8Hz), 4.45 (2H, s), 7.20-7.40 (5H, m), 7.64 (1H, s), 7.68 (1H, s).

Reference Example 181

参考例１７９で得た8-(4-クロロブタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-(2-メトキシフェニル)エチルアミン(1.63g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(797mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.41 (9H, s), 1.85-2.00 (2H, m), 2.71 (2H, t, J = 5.2Hz), 2.75-2.95 (4H, m), 3.01 (2H, t, J = 5.2Hz), 3.15-3.45 (6H, m), 3.83 (3H, s), 4.13 (2H, t, J = 5.8Hz), 6.80-6.90 (2H, m), 7.05-7.20 (2H, m), 7.66 (1H, s), 7.71 (1H, s). 2- (2-methoxyphenyl) ethyl [4-oxo-4- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) butyl ] Tert-butyl carbamate

8- (4-Chlorobutanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 179 and 2- The title compound (797 mg) was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using (2-methoxyphenyl) ethylamine (1.63 g).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.85-2.00 (2H, m), 2.71 (2H, t, J = 5.2Hz), 2.75-2.95 (4H, m), 3.01 (2H , t, J = 5.2Hz), 3.15-3.45 (6H, m), 3.83 (3H, s), 4.13 (2H, t, J = 5.8Hz), 6.80-6.90 (2H, m), 7.05-7.20 ( 2H, m), 7.66 (1H, s), 7.71 (1H, s).

Reference Example 182

参考例1で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびベンジルアミン(550mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(498mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.40-1.90 (4H, m), 1.45 (9H, s), 2.71 (2H, t, J = 7.4Hz), 2.80-3.35 (8H, m), 4.00-4.50 (4H, m), 7.15-7.40 (5H, m), 7.66 (1H, s), 7.70 (1H, s). Tert-butyl benzyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl] carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and benzylamine (500 mg) obtained in Reference Example 1 550 mg) was used in the same manner as in Reference Example 19 to give the titled compound (498 mg) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.40-1.90 (4H, m), 1.45 (9H, s), 2.71 (2H, t, J = 7.4Hz), 2.80-3.35 (8H, m), 4.00-4.50 (4H, m), 7.15-7.40 (5H, m), 7.66 (1H, s), 7.70 (1H, s).

Reference Example 183

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2-メトキシベンジルアミン(704mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(524mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.40-1.80 (4H, m), 1.41 (9H, s), 2.71 (2H, t, J = 7.6Hz), 2.80-3.40 (8H, m), 3.82 (3H, s), 4.00-4.50 (4H, m), 6.80-7.00 (2H, m), 7.05-7.30 (2H, m), 7.67 (1H, s), 7.71 (1H, s). 2-methoxybenzyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl] carbamic acid tert- Butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 2-methoxy obtained in Reference Example 1 The same operation as in Reference Example 19 was carried out using benzylamine (704 mg) to give the title compound (524 mg) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.40-1.80 (4H, m), 1.41 (9H, s), 2.71 (2H, t, J = 7.6Hz), 2.80-3.40 (8H, m), 3.82 (3H , s), 4.00-4.50 (4H, m), 6.80-7.00 (2H, m), 7.05-7.30 (2H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 184

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) およびベンジルアミン(643mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(554mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.10-1.80 (6H, m), 1.45 (9H, s), 2.71 (2H, t, J = 7.6Hz), 2.68 (2H, t, J = 7.6Hz), 3.02 (2H, t, J = 7.6Hz), 3.10-3.30 (4H, m), 4.13 (2H, t, J = 8.8Hz), 4.42 (2H, s), 7.15-7.40 (5H, m), 7.67 (1H, s), 7.71 (1H, s). Tert-butyl benzyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl] carbamate

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) and benzylamine (700 mg) obtained in Reference Example 2 643 mg) was used in the same manner as in Reference Example 19 to give the titled compound (554 mg) as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.10-1.80 (6H, m), 1.45 (9H, s), 2.71 (2H, t, J = 7.6Hz), 2.68 (2H, t, J = 7.6Hz), 3.02 (2H, t, J = 7.6Hz), 3.10-3.30 (4H, m), 4.13 (2H, t, J = 8.8Hz), 4.42 (2H, s), 7.15-7.40 (5H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 185

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg)および2-メトキシベンジルアミン(704mg)を用いて、参考例１９と同様の操作を行うことにより、表題化合物(486mg)を淡黄色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.15-1.60 (4H, m), 1.42 (9H, s), 2.72 (2H, quintet, J = 7.5Hz), 2.71 (2H, t, J = 7.5Hz), 2.88 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.5Hz), 3.10-3.30 (4H, m), 3.82 (3H, s), 4.13 (2H, t, J = 8.4Hz), 4.40-4.50 (2H, m), 6.80-6.95 (2H, m), 7.10-7.30 (2H, m), 7.67 (1H, s), 7.71 (1H, s). 2-methoxybenzyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl] carbamic acid tert- Butyl

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and 2-methoxy obtained in Reference Example 2 The same operation as in Reference Example 19 was carried out using benzylamine (704 mg) to give the title compound (486 mg) as a pale yellow oil.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.15-1.60 (4H, m), 1.42 (9H, s), 2.72 (2H, quintet, J = 7.5Hz), 2.71 (2H, t, J = 7.5Hz), 2.88 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.5Hz), 3.10-3.30 (4H, m), 3.82 (3H, s), 4.13 (2H, t, J = 8.4Hz ), 4.40-4.50 (2H, m), 6.80-6.95 (2H, m), 7.10-7.30 (2H, m), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 186

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オン(1.00g) および2-フェニルエチルアミン(800mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(842mg) を淡黄色油状物として得た。
¹H NMR (300MHz, CDCl₃) δ 1.20-1.85 (6H, m), 1.47 (9H, s), 2.75-2.95 (4H, m), 3.00-3.25 (2H, m), 3.30-3.45 (2H, m), 4.68 (2H, s), 7.00 (1H, d, J = 8.7Hz), 7.10-7.35 (5H, m), 7.50-7.65 (2H, m), 8.90-9.25 (1H, br). Tert-Butyl 6-oxo-6- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) hexyl (2-phenylethyl) carbamate

Using 6- (6-bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one (1.00 g) and 2-phenylethylamine (800 mg) obtained in Reference Example 8, Reference Example 19 The title compound (842 mg) was obtained as a pale yellow oil by the same procedure as in.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.20-1.85 (6H, m), 1.47 (9H, s), 2.75-2.95 (4H, m), 3.00-3.25 (2H, m), 3.30-3.45 (2H, m), 4.68 (2H, s), 7.00 (1H, d, J = 8.7Hz), 7.10-7.35 (5H, m), 7.50-7.65 (2H, m), 8.90-9.25 (1H, br).

Reference Example 187

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オン(1.00g) および2-(2-メトキシフェニル)エチルアミン(925mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(974mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.20-1.85 (6H, m), 1.46 (9H, s), 2.75-2.95 (4H, m), 3.00-3.25 (2H, m), 3.30-3.45 (2H, m), 3.82 (3H, s), 4.68 (2H, s), 6.80-7.25 (5H, m), 7.50-7.65 (2H, m), 8.90-9.30 (1H, br). Tert-Butyl 2- (2-methoxyphenyl) ethyl [6-oxo-6- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) hexyl] carbamate

Using 6- (6-bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one (1.00 g) and 2- (2-methoxyphenyl) ethylamine (925 mg) obtained in Reference Example 8 In the same manner as in Reference Example 19, the title compound (974 mg) was obtained as a pale yellow oil.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-1.85 (6H, m), 1.46 (9H, s), 2.75-2.95 (4H, m), 3.00-3.25 (2H, m), 3.30-3.45 (2H, m), 3.82 (3H, s), 4.68 (2H, s), 6.80-7.25 (5H, m), 7.50-7.65 (2H, m), 8.90-9.30 (1H, br).

Reference Example 188

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オン(1.00g) および2-(2-クロロフェニル)エチルアミン(952mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(974mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.20-1.85 (6H, m), 1.44 (9H, s), 2.80-3.25 (6H, m), 3.35-4.45 (2H, m), 4.69 (2H, s), 6.95-7.40 (5H, m), 7.50-7.65 (2H, m), 9.00-9.40 (1H, br). Tert-Butyl 2- (2-chlorophenyl) ethyl [6-oxo-6- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) hexyl] carbamate

Using 6- (6-bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one (1.00 g) and 2- (2-chlorophenyl) ethylamine (952 mg) obtained in Reference Example 8 The title compound (974 mg) was obtained as a pale yellow oil by the same operations as in Reference Example 19.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-1.85 (6H, m), 1.44 (9H, s), 2.80-3.25 (6H, m), 3.35-4.45 (2H, m), 4.69 (2H, s) , 6.95-7.40 (5H, m), 7.50-7.65 (2H, m), 9.00-9.40 (1H, br).

Reference Example 189

3-(1-アセチル-4-ピペリジニル)プロピオン酸(10.0g) を塩化チオニル(30ml) に室温にて少量ずつ加えた。室温で３０分攪拌後、塩化チオニルを減圧下留去し、3-(1-アセチル-4-ピペリジニル)プロピオニルクロリドの粗成績体を得た。該粗成績体および2,2,2-トリフルオロ-N-(2-メトキシフェニル)アセトアミド(10.0g) の1,2-ジクロロエタン(50ml) 懸濁液に、塩化アルミニウム(20g) を室温にて少量ずつ加えた。室温で１時間攪拌後、反応溶液を氷(200g) に注ぎ、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去し、得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル)にて精製し、溶媒を留去することにより、表題化合物を融点77-79℃の無色結晶(8.83g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.00-1.30 (3H, m), 1.50-1.90 (4H, m), 2.09 (3H, s), 2.53 (1H, tt, J = 12.8, 2.8Hz), 2.90-3.05 (3H, m), 3.70-3.90 (1H, m), 4.02 (3H, s), 4.50-4.70 (1H, m), 7.02 (1H, d, J = 8.8Hz), 7.89 (1H, dd, J = 8.8, 2.2Hz), 8.50-8.65 (1H, br), 8.95 (1H, d, J = 2.2Hz). N- {5- [3- (1-acetyl-4-piperidinyl) propanoyl] -2-methoxyphenyl} -2,2,2-trifluoroacetamide

3- (1-Acetyl-4-piperidinyl) propionic acid (10.0 g) was added in portions to thionyl chloride (30 ml) at room temperature. After stirring at room temperature for 30 minutes, thionyl chloride was distilled off under reduced pressure to obtain a crude product of 3- (1-acetyl-4-piperidinyl) propionyl chloride. A suspension of the crude product and 2,2,2-trifluoro-N- (2-methoxyphenyl) acetamide (10.0 g) in 1,2-dichloroethane (50 ml) was charged with aluminum chloride (20 g) at room temperature. Added in small portions. After stirring at room temperature for 1 hour, the reaction solution was poured into ice (200 g), extracted with ethyl acetate, and washed with saturated brine. After drying the organic layer over magnesium sulfate, the solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel chromatography (developing solvent; ethyl acetate). Obtained as colorless crystals (8.83 g) at 77-79 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.00-1.30 (3H, m), 1.50-1.90 (4H, m), 2.09 (3H, s), 2.53 (1H, tt, J = 12.8, 2.8Hz), 2.90 -3.05 (3H, m), 3.70-3.90 (1H, m), 4.02 (3H, s), 4.50-4.70 (1H, m), 7.02 (1H, d, J = 8.8Hz), 7.89 (1H, dd , J = 8.8, 2.2Hz), 8.50-8.65 (1H, br), 8.95 (1H, d, J = 2.2Hz).

Reference Example 190

参考例１８９で得たN-{5-[3-(1-アセチル-4-ピペリジニル)プロパノイル]-2-メトキシフェニル}-2,2,2-トリフルオロアセトアミド(3.00g) の飽和炭酸カリウム水溶液(20ml)、水(10ml)、およびメタノール(30ml)懸濁液を室温で５時間攪拌した。メタノールを減圧下留去し、残渣を酢酸エチルで抽出後、飽和食塩水で洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより、表題化合物を融点101-103℃の無色結晶(1.57g)として得た。
¹H NMR (200MHz, CDCl₃) δ 1.00-1.25 (3H, m), 1.45-1.85 (4H, m), 2.08 (3H, s), 2.52 (1H, tt, J = 12.8, 3.0Hz), 2.85-3.10 (3H, m), 3.70-3.90 (1H, m), 3.91 (3H, s), 3.90-4.00 (2H, br), 4.50-4.70 (1H, m), 6.80 (1H, d, J = 8.4Hz), 7.30-7.45 (2H, m).
元素分析 C₁₇H₂₄N₂O₃として
計算値：C, 67.08; H, 7.95; N, 9.20.
実験値：C, 66.83; H, 7.73; N, 9.18. 3- (1-acetyl-4-piperidinyl) -1- (3-amino-4-methoxyphenyl) -1-propanone

Saturated aqueous potassium carbonate solution of N- {5- [3- (1-acetyl-4-piperidinyl) propanoyl] -2-methoxyphenyl} -2,2,2-trifluoroacetamide (3.00 g) obtained in Reference Example 189 A suspension of (20 ml), water (10 ml), and methanol (30 ml) was stirred at room temperature for 5 hours. Methanol was distilled off under reduced pressure, and the residue was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as colorless crystals (1.57 g) having a melting point of 101-103 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.00-1.25 (3H, m), 1.45-1.85 (4H, m), 2.08 (3H, s), 2.52 (1H, tt, J = 12.8, 3.0Hz), 2.85 -3.10 (3H, m), 3.70-3.90 (1H, m), 3.91 (3H, s), 3.90-4.00 (2H, br), 4.50-4.70 (1H, m), 6.80 (1H, d, J = 8.4Hz), 7.30-7.45 (2H, m).
Elemental analysis Calculated as C ₁₇ H ₂₄ N ₂ O ₃ : C, 67.08; H, 7.95; N, 9.20.
Experimental value: C, 66.83; H, 7.73; N, 9.18.

Reference Example 191

参考例１９０で得た3-(1-アセチル-4-ピペリジニル)-1-(3-アミノ-4-メトキシフェニル)-1-プロパノン(500mg) の濃塩酸(10ml) 溶液を130℃にて６時間攪拌した。溶媒を留去した後、残渣を濾取し、エタノールおよびジエチルエーテルで順次洗浄した。得られた結晶を風乾することにより、表題化合物を融点210℃(分解) の無色結晶(544mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.25-1.45 (2H, m), 1.50-1.65 (3H, m), 1.75-1.90 (2H, m), 2.70-2.90 (2H, m), 2.97 (2H, t, J = 6.9Hz), 3.15-3.25 (2H, m), 3.94 (3H, s), 7.00-9.50 2H, br), 7.20 (1H, d, J = 8.4Hz), 7.80-7.90 (2H, m), 8.75-9.25 (3H, br). 1- (3-Amino-4-methoxyphenyl) -3- (4-piperidinyl) -1-propanone dihydrochloride

A solution of 3- (1-acetyl-4-piperidinyl) -1- (3-amino-4-methoxyphenyl) -1-propanone (500 mg) obtained in Reference Example 190 in concentrated hydrochloric acid (10 ml) was added at 130 ° C. Stir for hours. After the solvent was distilled off, the residue was collected by filtration and washed successively with ethanol and diethyl ether. The obtained crystals were air-dried to obtain the title compound as colorless crystals (544 mg) having a melting point of 210 ° C. (decomposition).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.25-1.45 (2H, m), 1.50-1.65 (3H, m), 1.75-1.90 (2H, m), 2.70-2.90 (2H, m), 2.97 ( 2H, t, J = 6.9Hz), 3.15-3.25 (2H, m), 3.94 (3H, s), 7.00-9.50 2H, br), 7.20 (1H, d, J = 8.4Hz), 7.80-7.90 ( 2H, m), 8.75-9.25 (3H, br).

Reference Example 192

1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(10.0g) および3-クロロプロパノイルクロリド(6.06ml) を用いて、参考例１と同様の操作を行うことにより、表題化合物(12.0g) を融点154-155℃の無色結晶として得た。
¹H NMR (300MHz, CDCl₃) δ 2.72 (2H, t, J = 7.8Hz), 3.03 (2H, t, J = 7.8Hz), 3.23 (2H, t, J = 8.7Hz), 3.39 (2H, t, J = 6.9Hz), 3.91 (2H, t, J = 6.9Hz), 4.13 (2H, t, J = 8.7Hz), 7.67 (1H, s), 7.71 (1H, s). 8- (3-Chloropropanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one

Using Reference Example 1 with 1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (10.0 g) and 3-chloropropanoyl chloride (6.06 ml) The same operation was performed to obtain the title compound (12.0 g) as colorless crystals having a melting point of 154-155 ° C.
¹ H NMR (300MHz, CDCl ₃ ) δ 2.72 (2H, t, J = 7.8Hz), 3.03 (2H, t, J = 7.8Hz), 3.23 (2H, t, J = 8.7Hz), 3.39 (2H, t, J = 6.9Hz), 3.91 (2H, t, J = 6.9Hz), 4.13 (2H, t, J = 8.7Hz), 7.67 (1H, s), 7.71 (1H, s).

Reference Example 193

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および(±)-2,3-ジヒドロ-1H-インデン-1-イルアミン(683mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(332mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.20-2.10 (13H, m), 2.60-3.10 (12H, m), 3.10-3.30 (2H, m), 3.50-3.65 (1H, m), 4.00-4.20 (2H, m), 7.10-7.30 (3H, m), 7.60-7.80 (3H, m). (±) -2,3-Dihydro-1H-inden-1-yl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij ] Quinolin-8-yl) pentyl] tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and (±) obtained in Reference Example 1 The title compound (332 mg) was obtained as a pale yellow oil by the same procedure as in Reference Example 19 using -2,3-dihydro-1H-inden-1-ylamine (683 mg).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.20-2.10 (13H, m), 2.60-3.10 (12H, m), 3.10-3.30 (2H, m), 3.50-3.65 (1H, m), 4.00-4.20 ( 2H, m), 7.10-7.30 (3H, m), 7.60-7.80 (3H, m).

Reference Example 194

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2,3-ジヒドロ-1H-インデン-2-イルアミン(683mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(461mg) を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.42 (9H, s), 1.50-1.75 (2H, m), 1.80-2.00 (2H, m), 2.72 (2H, t, J = 7.6Hz), 2.80-3.30 (11H, m), 3.50-3.65 (1H, m), 4.00-4.20 (3H, m), 7.05-7.20 (4H, m), 7.60-7.75 (2H, m). 2,3-Dihydro-1H-inden-2-yl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8 -Yl) pentyl] tert-butyl carbamate

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 2,3 obtained in Reference Example 1 The title compound (461 mg) was obtained as a pale yellow oil by the same procedure as in Reference Example 19 using -dihydro-1H-inden-2-ylamine (683 mg).
¹ H NMR (200MHz, CDCl ₃ ) δ 1.42 (9H, s), 1.50-1.75 (2H, m), 1.80-2.00 (2H, m), 2.72 (2H, t, J = 7.6Hz), 2.80-3.30 (11H, m), 3.50-3.65 (1H, m), 4.00-4.20 (3H, m), 7.05-7.20 (4H, m), 7.60-7.75 (2H, m).

Reference Example 195

3,4-ジヒドロキノリン-2(1H)-オン(2.94g)および塩化5-クロロペンタノイル(3.7g)を用いて、参考例1と同様の操作を行うことにより、表題化合物を融点145-146℃の無色結晶(1.59g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.84-1.94 (4H, m), 2.67 (2H, t, J = 6.4Hz), 2.96 (2H, t, J = 6.8Hz), 3.05 (2H, t, J = 7.5Hz), 3.59 (2H, t, J = 6.4Hz), 6.90 (1H, d, J = 8.7Hz), 7.81 (1H, d, J = 8.7Hz), 7.82 (1H, s), 9.28 (1H, s).
IR (KBr) νcm^-1: 3273, 1680, 1604, 1361, 1314, 1227, 1145. 6- (5-Chloropentanoyl) -3,4-dihydroquinolin-2 (1H) -one

Using the same procedure as in Reference Example 1 using 3,4-dihydroquinolin-2 (1H) -one (2.94 g) and 5-chloropentanoyl chloride (3.7 g), the title compound was dissolved at a melting point of 145- Obtained as colorless crystals (1.59 g) at 146 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.84-1.94 (4H, m), 2.67 (2H, t, J = 6.4Hz), 2.96 (2H, t, J = 6.8Hz), 3.05 (2H, t, J = 7.5Hz), 3.59 (2H, t, J = 6.4Hz), 6.90 (1H, d, J = 8.7Hz), 7.81 (1H, d, J = 8.7Hz), 7.82 (1H, s), 9.28 ( 1H, s).
IR (KBr) νcm ^-1 : 3273, 1680, 1604, 1361, 1314, 1227, 1145.

Reference Example 196

参考例１９５で得た6-(5-クロロペンタノイル)-3,4-ジヒドロキノリン-2(1H)-オン(399mg) および2-フェニルエチルアミン(454mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(530mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.44 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7Hz), 2.75-2.86 (2H, m), 2.88-2.98 (2H, m), 3.03 (2H, t, J = 7Hz), 3.08-3.24 (2H, m), 3.32-3.42 (2H, m), 6.87 (1H, d, J = 8.4Hz), 7.18-7.30 (5H, m), 7.79 (1H, d, J = 6Hz), 7.80 (1H, s), 9.09 (1H, br). 5-Oxo-5- (2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) pentyl (2-phenylethyl) carbamate tert-butyl

Using 6- (5-chloropentanoyl) -3,4-dihydroquinolin-2 (1H) -one (399 mg) and 2-phenylethylamine (454 mg) obtained in Reference Example 195, the same as in Reference Example 19 By performing the operation, the title compound (530 mg) was obtained as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.44 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7Hz), 2.75-2.86 (2H, m), 2.88-2.98 ( 2H, m), 3.03 (2H, t, J = 7Hz), 3.08-3.24 (2H, m), 3.32-3.42 (2H, m), 6.87 (1H, d, J = 8.4Hz), 7.18-7.30 ( 5H, m), 7.79 (1H, d, J = 6Hz), 7.80 (1H, s), 9.09 (1H, br).

Reference Example 197

参考例１９５で得た6-(5-クロロペンタノイル)-3,4-ジヒドロキノリン-2(1H)-オン(399mg) および2-(2-メトキシフェニル)エチルアミン(567mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(638mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (9H, s), 1.51-1.72 (4H, m), 2.68 (2H, t, J = 8Hz), 2.78-2.88 (2H, m), 2.89-2.97 (2H, m), 3.03 (2H, t, J = 7.3Hz), 3.08-3.28 (2H, m), 3.30-3.42 (2H, m), 3.82 (3H, s) 6.83 (1H, d, J = 8.4Hz), 6.87-6.90 (2H, m), 7.09-7.21 (2H, m), 7.79 (1H, d, J = 6Hz), 7.80 (1H, s) 9.31 (1H, br). Tert-Butyl 2- (2-methoxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) pentyl] carbamate

Using 6- (5-chloropentanoyl) -3,4-dihydroquinolin-2 (1H) -one (399 mg) and 2- (2-methoxyphenyl) ethylamine (567 mg) obtained in Reference Example 195, The same operation as in Example 19 was performed to give the title compound (638 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.72 (4H, m), 2.68 (2H, t, J = 8Hz), 2.78-2.88 (2H, m), 2.89-2.97 ( 2H, m), 3.03 (2H, t, J = 7.3Hz), 3.08-3.28 (2H, m), 3.30-3.42 (2H, m), 3.82 (3H, s) 6.83 (1H, d, J = 8.4 Hz), 6.87-6.90 (2H, m), 7.09-7.21 (2H, m), 7.79 (1H, d, J = 6Hz), 7.80 (1H, s) 9.31 (1H, br).

Reference Example 198

参考例１９５で得た6-(5-クロロペンタノイル)-3,4-ジヒドロキノリン-2(1H)-オン(399mg) および2-(2-クロロフェニル)エチルアミン(584mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(682mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7.3Hz), 2.91-3.01 (4H, m), 3.03 (2H, t, J = 7.3Hz), 3.12-3.25 (2H, m), 3.41 (2H, t, J = 7.3Hz), 6.87 (1H, d, J = 8.4Hz), 7.17-7.20 (3H, m), 7.33 (1H, d, J = 7Hz), 7.80 (1H, d, J = 6Hz), 7.81 (1H, s) 9.01 (1H, br). 2- (2-Chlorophenyl) ethyl [5-oxo-5- (2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) pentyl] carbamate tert-butyl

Using 6- (5-chloropentanoyl) -3,4-dihydroquinolin-2 (1H) -one (399 mg) and 2- (2-chlorophenyl) ethylamine (584 mg) obtained in Reference Example 195, Reference Example The same operation as in 19 was carried out to give the title compound (682 mg) as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.68 (2H, t, J = 7.3Hz), 2.91-3.01 (4H, m), 3.03 (2H , t, J = 7.3Hz), 3.12-3.25 (2H, m), 3.41 (2H, t, J = 7.3Hz), 6.87 (1H, d, J = 8.4Hz), 7.17-7.20 (3H, m) , 7.33 (1H, d, J = 7Hz), 7.80 (1H, d, J = 6Hz), 7.81 (1H, s) 9.01 (1H, br).

Reference Example 199

3,4-ジヒドロキノリン-2(1H)-オン(2.94g)および塩化6-ブロモヘキサノイル(5.1g)を用いて、参考例1と同様の操作を行うことにより、表題化合物を融点116-117℃の無色結晶(1.62g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.50-1.57 (2H, m), 1.73-1.79 (2H, m), 1.88-1.96 (2H, m), 2.69 (2H, t, J = 6.4Hz), 2.95 (2H, t, J = 7.5Hz), 3.05 (2H, t, J = 7.5Hz), 3.43 (2H, t, J = 6.4Hz), 6.92 (1H, d, J = 8.7Hz), 7.80 (1H, d, J = 8.7Hz), 7.85 (1H, s), 9.51 (1H, s).
IR (KBr) νcm^-1: 3192, 3055, 1679, 1593, 1367, 1321, 1254. 6- (6-Bromohexanoyl) -3,4-dihydroquinolin-2 (1H) -one

The title compound was converted to the melting point 116- using the same procedure as in Reference Example 1 using 3,4-dihydroquinolin-2 (1H) -one (2.94 g) and 6-bromohexanoyl chloride (5.1 g). Obtained as colorless crystals (1.62 g) at 117 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.50-1.57 (2H, m), 1.73-1.79 (2H, m), 1.88-1.96 (2H, m), 2.69 (2H, t, J = 6.4Hz), 2.95 (2H, t, J = 7.5Hz), 3.05 (2H, t, J = 7.5Hz), 3.43 (2H, t, J = 6.4Hz), 6.92 (1H, d, J = 8.7Hz), 7.80 (1H , d, J = 8.7Hz), 7.85 (1H, s), 9.51 (1H, s).
IR (KBr) νcm ^-1 : 3192, 3055, 1679, 1593, 1367, 1321, 1254.

Reference Example 200

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン(224mg)および2-(2-メトキシフェニル)エチルアミン(266mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(230mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (9H, s), 1.51-1.76 (4H, m), 2.68 (2H, t, J = 7Hz), 2.77-2.88 (2H, m), 2.96 (4H, t, J = 7Hz), 3.12-3.24 (2H, m), 3.32-3.37 (2H, m), 3.38 (3H, s), 3.82 (3H, s), 6.83-6.89 (2H, m), 7.01 (1H, d, J = 8.5Hz), 7.06-7.21 (2H, m), 7.78 (1H, s) 7.87 (1H, d, J = 8Hz). 2- (2-Methoxyphenyl) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl] carbamate tert-butyl

6- (5-Chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (224 mg) and 2- (2-methoxyphenyl) ethylamine (266 mg) obtained in Reference Example 154 were used. Using the same procedure as in Reference Example 19, the title compound (230 mg) was obtained as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.51-1.76 (4H, m), 2.68 (2H, t, J = 7Hz), 2.77-2.88 (2H, m), 2.96 (4H, t, J = 7Hz), 3.12-3.24 (2H, m), 3.32-3.37 (2H, m), 3.38 (3H, s), 3.82 (3H, s), 6.83-6.89 (2H, m), 7.01 ( 1H, d, J = 8.5Hz), 7.06-7.21 (2H, m), 7.78 (1H, s) 7.87 (1H, d, J = 8Hz).

Reference Example 201

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン(224mg) および2-(2-クロロフェニル)エチルアミン(274mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(244mg) を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.76 (4H, m), 2.68 (2H, t, J = 7Hz), 2.92-2.98 (6H, m), 3.12-3.24 (2H, m), 3.39 (3H, s), 3.41 (2H, t, J = 7Hz), 7.02 (1H, d, J = 8.5Hz), 7.14-7.28 (3H, m), 7.33 (1H, d, J = 7Hz), 7.78 (1H, s,), 7.87 (1H, d, J = 8Hz). 2- (2-Chlorophenyl) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydro-6-quinolinyl) -5-oxopentyl] carbamate tert-butyl

Using 6- (5-chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (224 mg) and 2- (2-chlorophenyl) ethylamine (274 mg) obtained in Reference Example 154 In the same manner as in Reference Example 19, the title compound (244 mg) was obtained as a pale yellow oil.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.76 (4H, m), 2.68 (2H, t, J = 7Hz), 2.92-2.98 (6H, m), 3.12-3.24 ( 2H, m), 3.39 (3H, s), 3.41 (2H, t, J = 7Hz), 7.02 (1H, d, J = 8.5Hz), 7.14-7.28 (3H, m), 7.33 (1H, d, J = 7Hz), 7.78 (1H, s,), 7.87 (1H, d, J = 8Hz).

Reference Example 202

300mlの４口フラスコに5-オキソヘキサン酸エチル4.75g(30mmol)を仕込み、THF100mlを加えて溶解した。室温下N-メチル-2-(2-クロロフェニル)エチルアミン5.1g(30mmol)を加え、更にNaBH(OAc)₃ 8.3g(39mmol)を加えた。室温下一夜攪拌後、濃縮し残渣に6%重曹水各50mlを加えて中和した。遊離した油状物を酢酸エチル(50ml×2) で抽出し、MgSO₄で乾燥ののち濃縮することによって(±)-[[2-(2-クロロフェニル)エチル](メチル)アミノ]ヘキサン酸5-エチルを淡黄色油状物(6.38g)として得た。
¹H NMR (400MHz, CDCl₃) δ 0.94 (3H, d, J = 6.6Hz), 1.19-1.28 (1H, m), 1.25 (3H, t, J = 7.0Hz), 1.44-1.52 (1H, m), 1.56-1.64 (2H, m), 2.25 (2H, t, J = 7.3Hz), 2.29 (3H, s), 2.51-2.69 (3H, m), 2.84-2.89 (2H, m), 4.12 (2H, q, J = 7.0Hz), 7.12-7.25 (3H, m), 7.32 (1H, dd, J = 7.6, 1.5Hz).
IR (neat) νcm^-1: 1735, 1652, 1476, 1249, 1177, 1053, 752.
100mlのナス型コルベンに(±)-[[2-(2-クロロフェニル)エチル](メチル)アミノ]ヘキサン酸5-エチル6.2g (20mmol)を仕込み、EtOH (10ml)を加えて溶解した。室温下水10mlに溶解したKOH 1.35g(24mmol)を加えた。室温下16時間攪拌後EtOHを留去し、残渣に6N-塩酸4ml(24mmol)を加えて中和したのち濃縮乾固し、残渣にEtOH20mlを加えて溶解した。不溶物をろ去し、ろ液を濃縮乾固することによって表題化合物を淡黄色油状物(6.16g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.21 (3H, d, J = 6.6Hz), 1.41-1.51 (1H, m), 1.65-1.74 (2H,m), 1.99-2.01 (1H, m), 2.24-2.41 (2H, m), 2.61(3H, s), 2.92-3.04 (3H, m), 3.20 (2H, t, J = 8.3Hz), 7.16-7.23 (2H, m), 7.32-7.36 (2H, m), 9.35 (1H, br).
IR (neat) νcm^-1: 3418, 1718, 1630, 1476, 1398, 1053, 757. (±) -5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] hexanoic acid

To a 300 ml four-necked flask, 4.75 g (30 mmol) of ethyl 5-oxohexanoate was charged and dissolved by adding 100 ml of THF. At room temperature, 5.1 g (30 mmol) of N-methyl-2- (2-chlorophenyl) ethylamine was added, and 8.3 g (39 mmol) of NaBH (OAc) ₃ was further added. After stirring overnight at room temperature, the mixture was concentrated and neutralized by adding 50 ml of 6% sodium bicarbonate water to the residue. The liberated oil was extracted with ethyl acetate (50 ml × 2), dried over MgSO ₄ and concentrated to give (±)-[[2- (2-chlorophenyl) ethyl] (methyl) amino] hexanoic acid 5- Ethyl was obtained as a pale yellow oil (6.38 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 0.94 (3H, d, J = 6.6Hz), 1.19-1.28 (1H, m), 1.25 (3H, t, J = 7.0Hz), 1.44-1.52 (1H, m ), 1.56-1.64 (2H, m), 2.25 (2H, t, J = 7.3Hz), 2.29 (3H, s), 2.51-2.69 (3H, m), 2.84-2.89 (2H, m), 4.12 ( 2H, q, J = 7.0Hz), 7.12-7.25 (3H, m), 7.32 (1H, dd, J = 7.6, 1.5Hz).
IR (neat) νcm ^-1 : 1735, 1652, 1476, 1249, 1177, 1053, 752.
To 100 ml of eggplant colben was charged 6.2 g (20 mmol) of 5-ethyl (±)-[[2- (2-chlorophenyl) ethyl] (methyl) amino] hexanoate, and dissolved by adding EtOH (10 ml). 1.35 g (24 mmol) of KOH dissolved in 10 ml of water at room temperature was added. After stirring at room temperature for 16 hours, EtOH was distilled off. The residue was neutralized by adding 4 ml (24 mmol) of 6N-hydrochloric acid and concentrated to dryness, and 20 ml of EtOH was added to dissolve the residue. The insoluble material was removed by filtration, and the filtrate was concentrated to dryness to give the title compound as a pale yellow oil (6.16 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.21 (3H, d, J = 6.6Hz), 1.41-1.51 (1H, m), 1.65-1.74 (2H, m), 1.99-2.01 (1H, m), 2.24 -2.41 (2H, m), 2.61 (3H, s), 2.92-3.04 (3H, m), 3.20 (2H, t, J = 8.3Hz), 7.16-7.23 (2H, m), 7.32-7.36 (2H , m), 9.35 (1H, br).
IR (neat) νcm ^-1 : 3418, 1718, 1630, 1476, 1398, 1053, 757.

Reference Example 203

参考例６９で得た塩化5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホニル(5.06g) および40%メチルアミン-メタノール溶液(2.6g)を用いて参考例６６と同様の操作を行うことにより、表題化合物を融点120-121℃の無色結晶(4.82g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.85-1.92 (4H, m), 2.66 (3H, d, J = 5.4Hz), 2.98-3.01 (2H, m), 3.35 (2H, t, J = 8.8Hz), 3.57-3.60 (2H, m), 4.78 (1H, q, J = 5.4Hz), 4.88 (2H, t, J = 8.8Hz), 8.06 (1H, s), 8.22 (1H, s).
IR (KBr) νcm^-1: 3326, 1664, 1603, 1586, 1480, 1383, 1357, 1328, 1266, 1161, 1115, 868, 579. 5- (5-Chloropentanoyl) -N-methyl-2,3-dihydro-1-benzofuran-7-sulfonamide

Reference using 5- (5-chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonyl chloride (5.06 g) and 40% methylamine-methanol solution (2.6 g) obtained in Reference Example 69 The title compound was obtained as colorless crystals (4.82 g) having a melting point of 120-121 ° C. by carrying out the same operation as in Example 66.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.85-1.92 (4H, m), 2.66 (3H, d, J = 5.4Hz), 2.98-3.01 (2H, m), 3.35 (2H, t, J = 8.8Hz ), 3.57-3.60 (2H, m), 4.78 (1H, q, J = 5.4Hz), 4.88 (2H, t, J = 8.8Hz), 8.06 (1H, s), 8.22 (1H, s).
^{IR (KBr) νcm -1: 3326} , 1664, 1603, 1586, 1480, 1383, 1357, 1328, 1266, 1161, 1115, 868, 579.

Reference Example 204

参考例６９で得た塩化5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホニル(5.06g) およびジメチルアミン(3ml) を用いて、参考例６６と同様の操作を行うことにより、表題化合物を融点113-114℃の無色結晶(4.93g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.84-1.93(4H, m), 2.84 (6H, s), 2.96-3.00 (2H, m), 3.33 (2H, t, J = 8.8Hz), 3.57-3.60 (2H, m), 4.83 (2H, q, J = 5.4Hz), 8.03 (1H, s), 8.18 (1H, s).
IR (KBr) νcm^-1: 1681, 1603, 1479, 1462, 1422, 1340, 1264, 1154, 1119, 956, 710, 583. 5- (5-Chloropentanoyl) -N, N-dimethyl-2,3-dihydro-1-benzofuran-7-sulfonamide

Using 5- (5-chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonyl chloride (5.06 g) and dimethylamine (3 ml) obtained in Reference Example 69, the same as in Reference Example 66 By performing the operation, the title compound was obtained as colorless crystals (4.93 g) having a melting point of 113-114 ° C.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.84-1.93 (4H, m), 2.84 (6H, s), 2.96-3.00 (2H, m), 3.33 (2H, t, J = 8.8Hz), 3.57-3.60 (2H, m), 4.83 (2H, q, J = 5.4Hz), 8.03 (1H, s), 8.18 (1H, s).
IR (KBr) νcm ^-1 : 1681, 1603, 1479, 1462, 1422, 1340, 1264, 1154, 1119, 956, 710, 583.

Reference Example 205

2,2-ジメチル-2,3-ジヒドロ-1-ベンゾフラン(3.0g) および5-クロロバレリルクロリド(3.4g)を用いて、参考例１と同様の操作を行うことにより、表題化合物を微黄色油状物(3.6g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.50 (6H, s), 1.83-1.92 (4H, m), 2.91-2.95 (2H, m), 3.04 (2H, s), 3.56-3.59 (2H, m), 6.74 (1H, d, J = 8.8Hz), 7.79 (1H, d, J = 8.8Hz), 7.81 (1H, s).
IR (neat) νcm^-1: 1674, 1607, 1490, 1441, 1372, 1245, 1225, 1094, 868 5-Chloro-1- (2,3-dihydro-2,2-dimethyl-1-benzofuran-5-yl) pentan-1-one

By performing the same operation as in Reference Example 1 using 2,2-dimethyl-2,3-dihydro-1-benzofuran (3.0 g) and 5-chlorovaleryl chloride (3.4 g), Obtained as a yellow oil (3.6 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.50 (6H, s), 1.83-1.92 (4H, m), 2.91-2.95 (2H, m), 3.04 (2H, s), 3.56-3.59 (2H, m) , 6.74 (1H, d, J = 8.8Hz), 7.79 (1H, d, J = 8.8Hz), 7.81 (1H, s).
IR (neat) νcm ^-1 : 1674, 1607, 1490, 1441, 1372, 1245, 1225, 1094, 868

Reference Example 206

クロマン(5.40g) および5-クロロバレリルクロリド(6.82g)を用いて、参考例１と同様の操作を行うことにより、表題化合物を微黄色油状物(7.9g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.83-1.91 (4H, m), 2.00-2.06 (2H, m), 2.83 (2H, t, J = 6.6Hz), 2.91-2.96 (2H, m,) 3.58 (2H, t, J = 6.6Hz), 4.24 (2H, t, J = 5.2Hz), 6.81 (1H, d, J = 8.8Hz), 7.70 (1H, s), 7.71 (1H, d, J = 8.8Hz).
IR (neat) νcm^-1: 1675, 1606, 1577, 1499, 1317, 1247, 1162, 1133, 1118, 1060, 1005, 821. 5-Chloro-1- (3,4-dihydro-2H-chromen-6-yl) pentan-1-one

The title compound was obtained as a pale yellow oil (7.9 g) by the same procedures as in Reference Example 1 using chroman (5.40 g) and 5-chlorovaleryl chloride (6.82 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.83-1.91 (4H, m), 2.00-2.06 (2H, m), 2.83 (2H, t, J = 6.6Hz), 2.91-2.96 (2H, m,) 3.58 (2H, t, J = 6.6Hz), 4.24 (2H, t, J = 5.2Hz), 6.81 (1H, d, J = 8.8Hz), 7.70 (1H, s), 7.71 (1H, d, J = 8.8Hz).
IR (neat) νcm ^-1 : 1675, 1606, 1577, 1499, 1317, 1247, 1162, 1133, 1118, 1060, 1005, 821.

Reference Example 207

参考例２０６で得た5-クロロ-1-(3,4-ジヒドロ-2H-クロメン-6-イル)ペンタン-1-オン(5.1g)を用いて、参考例６５と同様の操作を行うことにより、表題化合物を無色油状物(3.57g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.85-1.94 (4H, m), 2.14-2.19 (2H, m), 2.93-3.00 (4H, m), 3.59 (2H, t, J = 5.9Hz), 4.54 (2H, t, J = 5.6Hz), 8.03 (1H, s), 8.33 (1H, s).
IR (neat) νcm^-1: 1686, 1600, 1567, 1485, 1371, 1278, 1258, 1172, 1132, 1002, 579, 557. 6- (5-Chloropentanoyl) chroman-8-sulfonyl chloride

The same operation as in Reference Example 65 is performed using 5-chloro-1- (3,4-dihydro-2H-chromen-6-yl) pentan-1-one (5.1 g) obtained in Reference Example 206. Gave the title compound as a colorless oil (3.57 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.85-1.94 (4H, m), 2.14-2.19 (2H, m), 2.93-3.00 (4H, m), 3.59 (2H, t, J = 5.9Hz), 4.54 (2H, t, J = 5.6Hz), 8.03 (1H, s), 8.33 (1H, s).
IR (neat) νcm ^-1 : 1686, 1600, 1567, 1485, 1371, 1278, 1258, 1172, 1132, 1002, 579, 557.

Reference Example 208

参考例２０７で得た塩化6-(5-クロロペンタノイル)-8-クロマンスルホニル(3.5g) を用いて、参考例６６と同様の操作を行うことにより、表題化合物を融点168-169℃の無色結晶(2.9g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.67-1.80 (4H, m), 1.97 (2H, t, J = 5.3Hz), 2.86 (2H, t, J = 6.1Hz), 3.00 (2H, t, J = 6.6Hz), 3.67 (2H, t, J = 6.1Hz), 4.36 (2H, t, J = 5.3Hz), 7.15 (2H, s), 7.94 (1H, d, J = 1.8Hz), 8.10 (1H, d, J = 1.8Hz).
IR (KBr) νcm^-1: 3376, 3272, 1695, 1599, 1482, 1459, 1419, 1309, 1244, 1137, 906, 744. 6- (5-Chloropentanoyl) -8-chromansulfonamide

Using the same procedure as in Reference Example 66 using 6- (5-chloropentanoyl) -8-chromansulfonyl chloride (3.5 g) obtained in Reference Example 207, the title compound was allowed to have a melting point of 168-169 ° C. Obtained as colorless crystals (2.9 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.67-1.80 (4H, m), 1.97 (2H, t, J = 5.3Hz), 2.86 (2H, t, J = 6.1Hz), 3.00 (2H, t, J = 6.6Hz), 3.67 (2H, t, J = 6.1Hz), 4.36 (2H, t, J = 5.3Hz), 7.15 (2H, s), 7.94 (1H, d, J = 1.8Hz), 8.10 ( (1H, d, J = 1.8Hz).
IR (KBr) νcm ^-1 : 3376, 3272, 1695, 1599, 1482, 1459, 1419, 1309, 1244, 1137, 906, 744.

Reference Example 209

参考例２０５で得た5-クロロ-1-(2,3-ジヒドロ-2,2-ジメチル-1-ベンゾフラン-5-イル)ペンタン-1-オン(543mg) および2-(2-クロロフェニル)エチルアミン(778mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を微黄色油状物(612mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.49 (6H, s), 1.51-1.72 (4H, m), 2.85-3.00 (4H, m), 3.03 (2H, s), 3.07-3.25 (2H, m), 3.41 (2H, t, J = 7.3Hz), 6.73 (1H, d, J = 9.1Hz), 7.12-7.34 (4H, m), 7.80 (2H, br.s). Tert-Butyl 5- (2,3-dihydro-2,2-dimethyl-1-benzofuran-5-yl) -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate

5-Chloro-1- (2,3-dihydro-2,2-dimethyl-1-benzofuran-5-yl) pentan-1-one (543 mg) and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 205 (778 mg) was used for the same operation as in Reference Example 19 to give the title compound as a pale yellow oil (612 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.49 (6H, s), 1.51-1.72 (4H, m), 2.85-3.00 (4H, m), 3.03 (2H, s), 3.07 -3.25 (2H, m), 3.41 (2H, t, J = 7.3Hz), 6.73 (1H, d, J = 9.1Hz), 7.12-7.34 (4H, m), 7.80 (2H, br.s).

Reference Example 210

参考例２０６で得た5-クロロ-1-(3,4-ジヒドロ-2H-クロメン-6-イル)ペンタン-1-オン(505mg) および2-(2-クロロフェニル)エチルアミン(778mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を微黄色油状物(793mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.01 (2H, t, J = 6Hz), 2.82 (2H, t, J = 6Hz), 2.85-3.01 (4H, m), 3.07-3.23 (2H, m), 3.41 (2H, t, J = 7Hz), 4.23 (2H, q, J = 5.3Hz), 6.80 (1H, d, J = 9.1Hz), 7.12-7.34 (4H, m), 7.70 (2H, br.s). Tert-Butyl 5- (3,4-dihydro-2H-chromen-6-yl) -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate

Using 5-chloro-1- (3,4-dihydro-2H-chromen-6-yl) pentan-1-one (505 mg) and 2- (2-chlorophenyl) ethylamine (778 mg) obtained in Reference Example 206 The title compound was obtained as a pale-yellow oil (793 mg) by the same operations as in Reference Example 19.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.01 (2H, t, J = 6Hz), 2.82 (2H, t, J = 6Hz), 2.85- 3.01 (4H, m), 3.07-3.23 (2H, m), 3.41 (2H, t, J = 7Hz), 4.23 (2H, q, J = 5.3Hz), 6.80 (1H, d, J = 9.1Hz) , 7.12-7.34 (4H, m), 7.70 (2H, br.s).

Reference Example 211

参考例２０３で得た5-(5-クロロペンタノイル)-N-メチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(664mg) および2-(2-メトキシフェニル)エチルアミン(762mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物(864mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (9H, s), 1.50-1.73 (4H, m), 2.65 (3H, d, J = 5.4Hz), 2.82 (2H, br.s), 2.95 (2H, br.s), 3.08-3.23 (2H, m), 3.31-3.37 (4H, m), 3.83 (3H, s), 4.81(1H, q, J = 5.4Hz), 4.86 (2H, t, J = 8.8Hz), 6.83-6.89 (2H, m), 7.09-7.21 (2H, m), 8.04 (1H, d, J = 1.5Hz), 8.22 (1H, d, J = 1.5Hz). 5- {7-[(Methylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

5- (5-Chloropentanoyl) -N-methyl-2,3-dihydro-1-benzofuran-7-sulfonamide (664 mg) and 2- (2-methoxyphenyl) ethylamine (762 mg) obtained in Reference Example 203 Was used to give the title compound as a colorless oil (864 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.50-1.73 (4H, m), 2.65 (3H, d, J = 5.4Hz), 2.82 (2H, br.s), 2.95 (2H , br.s), 3.08-3.23 (2H, m), 3.31-3.37 (4H, m), 3.83 (3H, s), 4.81 (1H, q, J = 5.4Hz), 4.86 (2H, t, J = 8.8Hz), 6.83-6.89 (2H, m), 7.09-7.21 (2H, m), 8.04 (1H, d, J = 1.5Hz), 8.22 (1H, d, J = 1.5Hz).

Reference Example 212

参考例２０３で得た5-(5-クロロペンタノイル)-N-メチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(664mg)および2-(2-クロロフェニル)エチルアミン(778mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点87-88℃の無色結晶(890mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.50-1.73 (4H, m), 2.66 (3H, d, J = 5.4Hz), 2.95 (4H, br.s), 3.08-3.27 (2H, m), 3.34 (2H, t, J = 8.8Hz), 3.41 (2H, t, J = 7.5Hz), 4.78 (1H, q, J = 5.4Hz), 4.87 (2H, t, J = 8.8Hz), 7.13-7.29 (3H, m), 7.33 (1H, d, J = 6.6Hz), 8.04 (1H, d, J = 1.2Hz), 8.22 (1H, d, J = 1.2Hz). 5- {7-[(Methylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate tert-butyl

5- (5-Chloropentanoyl) -N-methyl-2,3-dihydro-1-benzofuran-7-sulfonamide (664 mg) and 2- (2-chlorophenyl) ethylamine (778 mg) obtained in Reference Example 203 were used. And the title compound was obtained as colorless crystals (890 mg) having a melting point of 87-88 ° C. by the same procedure as in Reference Example 19.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.50-1.73 (4H, m), 2.66 (3H, d, J = 5.4Hz), 2.95 (4H, br.s), 3.08-3.27 (2H, m), 3.34 (2H, t, J = 8.8Hz), 3.41 (2H, t, J = 7.5Hz), 4.78 (1H, q, J = 5.4Hz), 4.87 (2H, t, J = 8.8Hz), 7.13-7.29 (3H, m), 7.33 (1H, d, J = 6.6Hz), 8.04 (1H, d, J = 1.2Hz), 8.22 (1H, d, J = 1.2Hz).

Reference Example 213

参考例２０４で得た5-(5-クロロペンタノイル)-N,N-ジメチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(692mg) および2-(2-メトキシフェニル)エチルアミン(762mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物(875mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (9H, s), 1.50-1.73 (4H, m), 2.79-2.87 (2H, m), 2.83(6H, s), 2.94 (2H, br.s), 3.08-3.23 (2H, m), 3.29-3.51 (4H, m), 3.83 (3H, s), 4.82 (2H, t, J = 8.8Hz), 6.83-6.88 (2H, m), 7.09-7.21 (2H, m), 8.01 (1H, d, J = 1.5Hz), 8.17 (1H, d, J = 1.5Hz). 5- {7-[(Dimethylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

5- (5-Chloropentanoyl) -N, N-dimethyl-2,3-dihydro-1-benzofuran-7-sulfonamide (692 mg) and 2- (2-methoxyphenyl) ethylamine (692 mg) obtained in Reference Example 204 The title compound was obtained as a colorless oil (875 mg) by the same procedures as in Reference Example 19 using 762 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.50-1.73 (4H, m), 2.79-2.87 (2H, m), 2.83 (6H, s), 2.94 (2H, br.s) , 3.08-3.23 (2H, m), 3.29-3.51 (4H, m), 3.83 (3H, s), 4.82 (2H, t, J = 8.8Hz), 6.83-6.88 (2H, m), 7.09-7.21 (2H, m), 8.01 (1H, d, J = 1.5Hz), 8.17 (1H, d, J = 1.5Hz).

Reference Example 214

参考例２０４で得た5-(5-クロロペンタノイル)-N,N-ジメチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(692mg)および2-(2-クロロフェニル)エチルアミン(778mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点86-87℃の無色結晶(960mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.50-1.73 (4H, m), 2.84 (6H, s), 2.95 (4H, br.s), 3.08-3.25 (2H, m), 3.32 (2H, t, J = 8.8Hz), 3.41 (2H, t, J = 7.5Hz), 4.82 (2H, t, J = 8.8Hz), 7.13-7.29 (3H, m), 7.33 (1H, d, J = 6.6Hz), 8.01 (1H, d, J = 1.4Hz), 8.17 (1H, d, J = 1.4Hz). 2- (2-Chlorophenyl) ethyl (5- {7-[(dimethylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl) carbamate tert-butyl

5- (5-Chloropentanoyl) -N, N-dimethyl-2,3-dihydro-1-benzofuran-7-sulfonamide (692 mg) and 2- (2-chlorophenyl) ethylamine (778 mg) obtained in Reference Example 204 ) To give the title compound as colorless crystals (960 mg) having a melting point of 86-87 ° C. by a similar operation as in Reference Example 19.
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.50-1.73 (4H, m), 2.84 (6H, s), 2.95 (4H, br.s), 3.08-3.25 (2H, m) , 3.32 (2H, t, J = 8.8Hz), 3.41 (2H, t, J = 7.5Hz), 4.82 (2H, t, J = 8.8Hz), 7.13-7.29 (3H, m), 7.33 (1H, d, J = 6.6Hz), 8.01 (1H, d, J = 1.4Hz), 8.17 (1H, d, J = 1.4Hz).

Reference Example 215

参考例２０８で得た6-(5-クロロペンタノイル)-8-クロマンスルホンアミド(664mg) および2-(2-メトキシフェニル)エチルアミン(762mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物650mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.40 (9H, s), 1.51-1.70 (4H, m), 2.11 (2H, br.s), 2.79-2.89 (6H, m), 3.07-3.23 (2H, m), 3.33 (2H, t, J = 7.1Hz), 3.82 (3H, s), 4.47 (2H, t, J = 5.1Hz), 5.29 (2H, s), 6.83-6.88 (2H, m), 7.06-7.20 (2H, m), 7.89 (1H, s), 8.27 (1H, s). 5- [8- (Aminosulfonyl) -3,4-dihydro-2H-chromen-6-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl

Using 6- (5-chloropentanoyl) -8-chromansulfonamide (664 mg) and 2- (2-methoxyphenyl) ethylamine (762 mg) obtained in Reference Example 208, the same operation as in Reference Example 19 is performed. This gave the title compound as a colorless oil (650 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.40 (9H, s), 1.51-1.70 (4H, m), 2.11 (2H, br.s), 2.79-2.89 (6H, m), 3.07-3.23 (2H, m), 3.33 (2H, t, J = 7.1Hz), 3.82 (3H, s), 4.47 (2H, t, J = 5.1Hz), 5.29 (2H, s), 6.83-6.88 (2H, m), 7.06-7.20 (2H, m), 7.89 (1H, s), 8.27 (1H, s).

Reference Example 216

参考例２０８で得た6-(5-クロロペンタノイル)-8-クロマンスルホンアミド(664mg) および2-(2-クロロフェニル)エチルアミン(778mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を無色油状物(677mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.38 (9H, s), 1.51-1.71 (4H, m), 2.12 (2H, br.s), 2.89-2.93 (6H, m), 3.11-3.21 (2H, m), 3.39 (2H, br.s), 4.47 (2H, t, J = 5.1Hz), 5.23 (2H, s), 7.13-7.34 (4H, m), 7.90 (1H, s), 8.27 (1H, s). 5- [8- (Aminosulfonyl) -3,4-dihydro-2H-chromen-6-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate tert-butyl

The same operation as in Reference Example 19 is carried out using 6- (5-chloropentanoyl) -8-chromansulfonamide (664 mg) and 2- (2-chlorophenyl) ethylamine (778 mg) obtained in Reference Example 208. Gave the title compound as a colorless oil (677 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.38 (9H, s), 1.51-1.71 (4H, m), 2.12 (2H, br.s), 2.89-2.93 (6H, m), 3.11-3.21 (2H, m), 3.39 (2H, br.s), 4.47 (2H, t, J = 5.1Hz), 5.23 (2H, s), 7.13-7.34 (4H, m), 7.90 (1H, s), 8.27 (1H , s).

Reference Example 217

1-メチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(4.45g) および5-クロロバレリルクロリド(5.58g)を用いて、参考例１と同様の操作を行うことにより、表題化合物の混合物（1.5：1）を無色結晶(5.5g)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.67-1.81 (4H, m), 2.99-3.05 (2H, m), 3.30 (3H×3/5, s), 3.32 (3H×2/5, s), 3.61-3.69 (2H, m,), 7.03 (1H×2/5, d, J = 8.3Hz), 7.14 (1H×3/5, d, J = 8.3Hz), 7.49 (1H×3/5, d, J = 1.5Hz), 7.64 (1H×2/5, d, J = 1.5Hz), 7.69 (1H×2/5, dd, J = 8.3, 1.5Hz), 7.73 (1H×3/5, dd, J = 8.8, 1.5Hz), 11.09 (1H×3/5, s), 11.23 (1H×2/5, s). 5- (5-chloropentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one and 6- (5-chloropentanoyl) -1-methyl-1,3-dihydro-2H -Benzimidazol-2-one

By performing the same operation as in Reference Example 1 using 1-methyl-1,3-dihydro-2H-benzimidazol-2-one (4.45 g) and 5-chlorovaleryl chloride (5.58 g), the title was obtained. A mixture of compounds (1.5: 1) was obtained as colorless crystals (5.5 g).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.67-1.81 (4H, m), 2.99-3.05 (2H, m), 3.30 (3H × 3/5, s), 3.32 (3H × 2/5, s ), 3.61-3.69 (2H, m,), 7.03 (1H × 2/5, d, J = 8.3Hz), 7.14 (1H × 3/5, d, J = 8.3Hz), 7.49 (1H × 3 / 5, d, J = 1.5Hz), 7.64 (1H × 2/5, d, J = 1.5Hz), 7.69 (1H × 2/5, dd, J = 8.3, 1.5Hz), 7.73 (1H × 3 / 5, dd, J = 8.8, 1.5Hz), 11.09 (1H × 3/5, s), 11.23 (1H × 2/5, s).

Reference Example 218

参考例２１７で得た5-(5-クロロペンタノイル)-1-メチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび6-(5-クロロペンタノイル)-1-メチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンの混合物(1.6g) および2-(2-クロロフェニル)エチルアミン(2.33g) を用いて、参考例１９と同様の操作を行うことにより、表題化合物を融点121-122℃の無色結晶(1-メチル体（Ａ）：1.0g)と微黄色油状物(3-メチル体（Ｂ）：645mg)として得た。
¹H NMR (1-メチル体（Ａ）；400MHz, CDCl₃) δ 1.41 (9H, s), 1.52-1.76 (4H, m), 2.97 (4H, br.s), 3.14-3.25 (2H, m), 3.42 (2H, t, J = 7.0Hz), 3.45 (3H, s), 6.98 (1H, d, J = 7.8Hz), 7.16-7.33 (4H, m), 7.75 (1H, s), 7.77 (1H, d, J = 7.8Hz), 10.76-10.84 (1H, m).
¹H NMR (3-メチル体（Ｂ）；400MHz, CDCl₃) δ 1.41 (9H, s), 1.52-1.76 (4H, m), 2.95-3.01 (4H, m), 3.15-3.25 (2H, m), 3.42 (2H, t, J = 7.3Hz), 3.48 (3H, s), 7.15 (1H, d, J = 8.0Hz), 7.16-7.34 (4H, m), 7.65 (1H, s), 7.76 (1H, d, J = 8.0Hz), 10.65 (1H, br.s). Tert-butyl 2- (2-chlorophenyl) ethyl [5- (1-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamate (A) and 2- (2-Chlorophenyl) ethyl [5- (3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamate tert-butyl (B)

5- (5-Chloropentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one and 6- (5-chloropentanoyl) -1-methyl-1 obtained in Reference Example 217 , 3-Dihydro-2H-benzimidazol-2-one mixture (1.6 g) and 2- (2-chlorophenyl) ethylamine (2.33 g) were used in the same manner as in Reference Example 19 to obtain the title compound. Were obtained as colorless crystals (1-methyl isomer (A): 1.0 g) and a pale yellow oil (3-methyl isomer (B): 645 mg) having a melting point of 121-122 ° C.
¹ H NMR (1-methyl form (A); 400 MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.52-1.76 (4H, m), 2.97 (4H, br.s), 3.14-3.25 (2H, m ), 3.42 (2H, t, J = 7.0Hz), 3.45 (3H, s), 6.98 (1H, d, J = 7.8Hz), 7.16-7.33 (4H, m), 7.75 (1H, s), 7.77 (1H, d, J = 7.8Hz), 10.76-10.84 (1H, m).
¹ H NMR (3-methyl form (B); 400 MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.52-1.76 (4H, m), 2.95-3.01 (4H, m), 3.15-3.25 (2H, m ), 3.42 (2H, t, J = 7.3Hz), 3.48 (3H, s), 7.15 (1H, d, J = 8.0Hz), 7.16-7.34 (4H, m), 7.65 (1H, s), 7.76 (1H, d, J = 8.0Hz), 10.65 (1H, br.s).

Reference Example 219

参考例２１７で得た5-(5-クロロペンタノイル)-1-メチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび6-(5-クロロペンタノイル)-1-メチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンの混合物(1.6g) および4-(2-アミノエチル)-3-クロロフェノール 臭化水素酸塩(3.3g) を用いて、参考例８２と同様の操作を行うことにより、表題化合物として、微黄色油状物(1-メチル体（Ａ）：428mg)と融点157-158℃の無色結晶(3-メチル体（Ｂ）：290mg)を得た。
¹H NMR (1-メチル体（Ａ）；400MHz, CDCl₃) δ 1.41 (9H, s), 1.51 (2H, br.s), 1.62-1.72 (2H, m), 2.84-2.91 (4H, m), 3.03-3.12 (2H, m), 3.36 (2H, t, J = 7.1Hz), 3.45 (3H, s), 6.72 (1H, d, J = 8.3Hz), 6.92 (1H,br.s), 6.97 (1H, d, J = 7.6Hz), 7.01 (1H, d, J = 8.3Hz), 7.67 (1H, br.s), 7.72 (1H, br.s), 7.77 (1H, d, J = 7.6Hz), 10.08-10.23 (1H, m).
¹H NMR (3-メチル体（Ｂ）；400MHz, CDCl₃) δ 1.29 (9H, s), 1.45-1.58 (4H, m), 2.74 (2H, t, J = 7.3Hz), 3.00 (2H, t, J = 6.6Hz), 3.05-3.17 (2H, m), 3.27 (2H, br.s), 3.32 (3H, s), 6.65 (1H, dd, J = 8.3, 2.4Hz), 6.77 (1H, d, J = 2.4Hz), 7.04 (2H, br.d, J = 8.0Hz), 7.64 (1H, br.s), 7.69 (1H, d, J = 8.0Hz), 9.66 (1H, s), 11.22 (1H, s). 2- (2-Chloro-4-hydroxyphenyl) ethyl [5- (1-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamic acid tert- Butyl (A) and 2- (2-chloro-4-hydroxyphenyl) ethyl [5- (3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl ] Tert-butyl carbamate (B)

5- (5-Chloropentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one and 6- (5-chloropentanoyl) -1-methyl-1 obtained in Reference Example 217 , 3-dihydro-2H-benzimidazol-2-one (1.6 g) and 4- (2-aminoethyl) -3-chlorophenol hydrobromide (3.3 g) By performing the same operation, a slightly yellow oily substance (1-methyl form (A): 428 mg) and colorless crystals (3-methyl form (B): 290 mg) having a melting point of 157-158 ° C. were obtained as the title compound. .
¹ H NMR (1-methyl form (A); 400 MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51 (2H, br.s), 1.62-1.72 (2H, m), 2.84-2.91 (4H, m ), 3.03-3.12 (2H, m), 3.36 (2H, t, J = 7.1Hz), 3.45 (3H, s), 6.72 (1H, d, J = 8.3Hz), 6.92 (1H, br.s) , 6.97 (1H, d, J = 7.6Hz), 7.01 (1H, d, J = 8.3Hz), 7.67 (1H, br.s), 7.72 (1H, br.s), 7.77 (1H, d, J = 7.6Hz), 10.08-10.23 (1H, m).
¹ H NMR (3-methyl form (B); 400 MHz, CDCl ₃ ) δ 1.29 (9H, s), 1.45-1.58 (4H, m), 2.74 (2H, t, J = 7.3 Hz), 3.00 (2H, t, J = 6.6Hz), 3.05-3.17 (2H, m), 3.27 (2H, br.s), 3.32 (3H, s), 6.65 (1H, dd, J = 8.3, 2.4Hz), 6.77 (1H , d, J = 2.4Hz), 7.04 (2H, br.d, J = 8.0Hz), 7.64 (1H, br.s), 7.69 (1H, d, J = 8.0Hz), 9.66 (1H, s) , 11.22 (1H, s).

Reference Example 220

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン(562mg)および4-(2-アミノエチル)-3-クロロフェノール 臭化水素酸塩(1.1g) を用いて、参考例８２と同様の操作を行うことにより、表題化合物を微黄色油状物(272mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.40 (9H, s), 1.60 (2H, br.s), 1.68-1.74 (2H, m), 2.85 (2H, m), 3.00 (2H, t, J = 7.3Hz), 3.18 (2H, t, J = 7.3Hz), 3.36 (2H, br.s), 3.46 (6H, s), 6.70 (1H, d, J = 8.0Hz), 6.90 (1H,br.s), 6.95-7.24 (3H, m), 7.62 (1H, d, J = 1.7Hz), 7.78 (1H, dd, J = 8.0, 1.7Hz). 2- (2-Chloro-4-hydroxyphenyl) ethyl [5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamic acid tert-butyl

5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one (562 mg) and 4- (2-aminoethyl) -3 obtained in Reference Example 10 The title compound was obtained as a pale-yellow oil (272 mg) by the same procedures as in Reference Example 82 using -chlorophenol hydrobromide (1.1 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.40 (9H, s), 1.60 (2H, br.s), 1.68-1.74 (2H, m), 2.85 (2H, m), 3.00 (2H, t, J = 7.3Hz), 3.18 (2H, t, J = 7.3Hz), 3.36 (2H, br.s), 3.46 (6H, s), 6.70 (1H, d, J = 8.0Hz), 6.90 (1H, br. s), 6.95-7.24 (3H, m), 7.62 (1H, d, J = 1.7Hz), 7.78 (1H, dd, J = 8.0, 1.7Hz).

Reference Example 221

5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン 2,2-ジオキシドを用いて、参考例１３２と同様の操作を行うことにより、表題化合物を融点103-104℃の褐色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 2.17 (2H, quintet, J = 6.2 Hz), 2.77 (2H, t, J = 6.4 Hz), 3.25 (3H, s), 3.69 (2H, t, J = 5.6 Hz), 6.56 (1H, d, J = 7.8 Hz), 6.74 (1H, d, J = 6.8 Hz), 6.88 (1H, t, J = 7.6 Hz). 1-Methyl-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinoline 2,2-dioxide

By performing the same operation as in Reference Example 132 using 5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinoline 2,2-dioxide, the title was obtained. The compound was obtained as brown crystals with a melting point of 103-104 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 2.17 (2H, quintet, J = 6.2 Hz), 2.77 (2H, t, J = 6.4 Hz), 3.25 (3H, s), 3.69 (2H, t, J = 5.6 Hz), 6.56 (1H, d, J = 7.8 Hz), 6.74 (1H, d, J = 6.8 Hz), 6.88 (1H, t, J = 7.6 Hz).

Reference Example 222

参考例２２１で得た1-メチル-5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン 2,2-ジオキシドおよび5-クロロバレリルクロリドを用い、参考例１と同様の操作を行うことにより、表題化合物を融点99-100℃の淡赤色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.89 (4H, t, J = 2.8 Hz), 2.21 (2H, quintet, J = 5.6 Hz), 2.83 (2H, t, J = 6.2 Hz), 2.96 (2H, t, J = 6.8 Hz), 3.21 (3H, s), 3.58 (2H, t, J = 6.8 Hz), 3.77 (2H, t, J = 5.6 Hz), 7.24 (1H, s), 7.44 (1H, s). 5-chloro-1- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinolin-8-yl) -1-pentanone

1-methyl-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinoline 2,2-dioxide and 5-chlorovaleryl chloride obtained in Reference Example 221 The title compound was obtained as pale red crystals having a melting point of 99-100 ° C. by carrying out the same operations as in Reference Example 1 using
¹ H NMR (200MHz, CDCl ₃ ) δ 1.89 (4H, t, J = 2.8 Hz), 2.21 (2H, quintet, J = 5.6 Hz), 2.83 (2H, t, J = 6.2 Hz), 2.96 (2H, t, J = 6.8 Hz), 3.21 (3H, s), 3.58 (2H, t, J = 6.8 Hz), 3.77 (2H, t, J = 5.6 Hz), 7.24 (1H, s), 7.44 (1H, s).

Reference Example 223

参考例２２２で得た5-クロロ-1-(1-メチル-2,2-ジオキシド-5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン-8-イル)-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用い、参考例１９と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR (200MHz, CDCl₃) δ 1.42 (9H, br), 1.53-1.71 (4H, m), 2.19 (2H, quintet, J = 5.6 Hz), 2.81 (2H, t, J = 6.2 Hz), 2.94 (4H, m), 3.22 (2H, m), 3.31 (3H, s), 3.41 (2H, t, J = 6.8 Hz), 3.75 (2H, t, J = 5.6 Hz), 7.15-7.35 (5H, m), 7.44 (1H, s). 2- (2-Chlorophenyl) ethyl [5- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinoline -8-yl) -5-oxopentyl] carbamate tert-butyl

5-Chloro-1- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] obtained in Reference Example 222 The title compound was obtained as a pale-yellow oil by the same procedures as in Reference Example 19 using quinolin-8-yl) -1-pentanone and 2- (2-chlorophenyl) ethylamine.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.42 (9H, br), 1.53-1.71 (4H, m), 2.19 (2H, quintet, J = 5.6 Hz), 2.81 (2H, t, J = 6.2 Hz), 2.94 (4H, m), 3.22 (2H, m), 3.31 (3H, s), 3.41 (2H, t, J = 6.8 Hz), 3.75 (2H, t, J = 5.6 Hz), 7.15-7.35 (5H , m), 7.44 (1H, s).

Reference Example 224

5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン 2,2-ジオキシドおよび5-クロロバレリルクロリドを用い、参考例１と同様の操作を行うことにより、表題化合物を融点118-119℃の淡赤色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.74 (4H, m), 2.06 (2H, t, J = 6.0 Hz), 2.77 (2H, t, J = 5.8 Hz), 2.99 (2H, t, J = 7.0 Hz), 3.65 (4H, m), 7.24 (1H, s), 7.53 (1H, s), 11.58 (1H, s). 5-Chloro-1- (2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinolin-8-yl) -1-pentanone

Operation similar to Reference Example 1 using 5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinoline 2,2-dioxide and 5-chlorovaleryl chloride To give the title compound as pale red crystals with a melting point of 118-119 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.74 (4H, m), 2.06 (2H, t, J = 6.0 Hz), 2.77 (2H, t, J = 5.8 Hz), 2.99 (2H, t, J = 7.0 Hz), 3.65 (4H, m), 7.24 (1H, s), 7.53 (1H, s), 11.58 (1H, s).

Reference Example 225

2-アミノベンジルアミンを用い、参考例１２６と同様の操作を行うことにより、表題化合物を融点178-180℃の淡黄色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 4.40 (2H, d, J = 7.8 Hz), 6.71 (1H, d, J = 7.0 Hz), 6.92 (1H, t, J = 7.2 Hz), 7.11-7.32 (3H, m), 10.16 (1H, s). 3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide

The title compound was obtained as pale-yellow crystals with a melting point of 178-180 ° C. by carrying out the same operation as in Reference Example 126 using 2-aminobenzylamine.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 4.40 (2H, d, J = 7.8 Hz), 6.71 (1H, d, J = 7.0 Hz), 6.92 (1H, t, J = 7.2 Hz), 7.11- 7.32 (3H, m), 10.16 (1H, s).

Reference Example 226

参考例２２５で得た3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン 2,2-ジオキシドおよび5-クロロバレリルクロリドを用い、参考例１と同様の操作を行うことにより、表題化合物を融点116-117℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.74 (4H, m), 2.98 (2H, t, J = 6.6 Hz), 3.68 (2H, t, J = 6.2 Hz), 4.48 (2H, d, J = 7.6 Hz), 6.78 (1H, d, J = 8.8 Hz), 7.17 (1H, m), 7.51 (1H, t, J = 8.0 Hz), 7.83 (1H, s), 10.81 (1H, s). 5-Chloro-1- (2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1-pentanone

By performing the same operation as in Reference Example 1 using 3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide and 5-chlorovaleryl chloride obtained in Reference Example 225 The title compound was obtained as colorless crystals having a melting point of 116-117 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.74 (4H, m), 2.98 (2H, t, J = 6.6 Hz), 3.68 (2H, t, J = 6.2 Hz), 4.48 (2H, d, J = 7.6 Hz), 6.78 (1H, d, J = 8.8 Hz), 7.17 (1H, m), 7.51 (1H, t, J = 8.0 Hz), 7.83 (1H, s), 10.81 (1H, s).

Reference Example 227

参考例２２５で得た3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン 2,2-ジオキシドを用い、参考例１２７と同様の操作を行うことにより、表題化合物を融点59-60℃の無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 2.77 (3H, s), 3.34 (3H, s), 4.62 (2H, s), 6.90 (1H, d, J = 7.6 Hz), 7.04 (2H, m), 7.30 (1H, d, J = 9.4 Hz). 1,3-Dimethyl-3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide

Using the 3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide obtained in Reference Example 225, the same operation as in Reference Example 127 was performed to give the title compound having a melting point of 59- Obtained as colorless crystals at 60 ° C.
¹ H NMR (200MHz, CDCl ₃ ) δ 2.77 (3H, s), 3.34 (3H, s), 4.62 (2H, s), 6.90 (1H, d, J = 7.6 Hz), 7.04 (2H, m), 7.30 (1H, d, J = 9.4 Hz).

Reference Example 228

参考例２２７で得た1,3-ジメチル-3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン 2,2-ジオキシドおよび5-クロロバレリルクロリドを用い、参考例１と同様の操作を行うことにより、表題化合物を融点78-79℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.75 (4H, m), 2.67 (3H, s), 3.03 (2H, t, J = 5.4 Hz), 3.32 (3H, s), 3.69 (2H, t, J = 5.4 Hz), 4.74 (2H, s), 7.15 (1H, d, J = 8.8 Hz), 7.84 (1H, s), 7.95 (1H, d, J = 8.8 Hz). 5-Chloro-1- (1,3-dimethyl-2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1-pentanone

Similar to Reference Example 1 using 1,3-dimethyl-3,4-dihydro-1H-2,1,3-benzothiadiazine 2,2-dioxide and 5-chlorovaleryl chloride obtained in Reference Example 227 The title compound was obtained as colorless crystals having a melting point of 78-79 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.75 (4H, m), 2.67 (3H, s), 3.03 (2H, t, J = 5.4 Hz), 3.32 (3H, s), 3.69 (2H, t , J = 5.4 Hz), 4.74 (2H, s), 7.15 (1H, d, J = 8.8 Hz), 7.84 (1H, s), 7.95 (1H, d, J = 8.8 Hz).

Reference Example 229

トリメリト酸無水物(30g) のテトラヒドロフラン(100ml) 溶液にメチルアミン水溶液(50ml) を加えた。室温で１５分攪拌後、常圧下加熱することにより溶媒を留去した。残渣に１規定塩酸を加えてpHを１とし、析出物を濾取し、水、エタノールおよびジエチルエーテルで順次洗浄した。さらに風乾させることにより、表題化合物を融点226-232℃無色結晶(11.6g) として得た。
¹H NMR (200MHz, DMSO-d₆) δ 3.06 (3H, s), 7.97 (1H, d, J = 7.6 Hz), 8.19 (1H, s), 8.33 (1H, dd, J = 7.7, 1.6 Hz), 8.00-10.00 (1H, br). 2-Methyl-1,3-dioxo-5-isoindolinecarboxylic acid

To a solution of trimellitic anhydride (30 g) in tetrahydrofuran (100 ml) was added aqueous methylamine solution (50 ml). After stirring at room temperature for 15 minutes, the solvent was distilled off by heating under normal pressure. 1N Hydrochloric acid was added to the residue to adjust the pH to 1, and the precipitate was collected by filtration and washed successively with water, ethanol and diethyl ether. Further, the title compound was obtained as colorless crystals (11.6 g) having a melting point of 226-232 ° C. by air drying.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 3.06 (3H, s), 7.97 (1H, d, J = 7.6 Hz), 8.19 (1H, s), 8.33 (1H, dd, J = 7.7, 1.6 Hz ), 8.00-10.00 (1H, br).

Reference Example 230

参考例２２９で得た2-メチル-1,3-ジオキソ-5-イソインドリンカルボン酸(9.2g) およびジメチルホルムアミド(触媒量) のテトラヒドロフラン(100ml) 溶液にオキザリルクロリド(5.86ml) を室温にて滴々加えた。室温で１時間攪拌後、溶媒を減圧下留去した。得られた残渣を濾取し、ジエチルエーテルで洗浄後、減圧下乾燥することにより、表題化合物を白色固形物として得た。
¹H NMR (200MHz, DMSO-d₆) δ 3.06 (3H, s), 7.97 (1H, d, J = 7.6 Hz), 8.19 (1H, s), 8.33 (1H, dd, J = 7.9, 1.0 Hz). 2-Methyl-1,3-dioxo-5-isoindoline carbonyl chloride

To a solution of 2-methyl-1,3-dioxo-5-isoindolinecarboxylic acid (9.2 g) and dimethylformamide (catalytic amount) obtained in Reference Example 229 in tetrahydrofuran (100 ml) was added oxalyl chloride (5.86 ml) at room temperature. And dripped. After stirring at room temperature for 1 hour, the solvent was distilled off under reduced pressure. The obtained residue was collected by filtration, washed with diethyl ether, and dried under reduced pressure to give the title compound as a white solid.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 3.06 (3H, s), 7.97 (1H, d, J = 7.6 Hz), 8.19 (1H, s), 8.33 (1H, dd, J = 7.9, 1.0 Hz ).

Reference Example 231

本化合物の合成はY. Tamaru らの方法(Tetrahedron Lett. 1985, 26(45), 5529)に準じて行った。すなわち、Ｚｎ−Ｃｕカップル(4.6g) および1-クロロ-4-ヨードブタン(10.0g) のトルエン(60ml) およびジメチルホルムアミド(6ml) 溶液を窒素雰囲気下６０℃で３時間攪拌した。次に参考例２３０で得た塩化2-メチル-1,3-ジオキソ-5-イソインドリンカルボニル(6.82g) およびテトラキストリフェニルホスフィンパラジウム(1.4g) のトルエン(30ml) 懸濁液を先の溶液に室温にて加えた。室温で１時間攪拌後、水で反応をクエンチし、溶媒を減圧下留去した。残渣に水を加え、酢酸エチルで抽出後、１規定塩酸、水、炭酸カリウム水、水、および飽和食塩水で順次洗浄した。有機層を硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより、表題化合物を融点97-98℃の無色結晶(5.15g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.65-1.90 (4H, m), 3.06 (3H, s), 3.22 (2H, t, J = 6.8 Hz), 3.71 (2H, t, J = 6.2 Hz), 7.98 (1H, d, J = 7.6 Hz), 8.25-8.40 (2H, m). 5- (5-Chloropentanoyl) -2-methyl-1H-isoindole-1,3 (2H) -dione

This compound was synthesized according to the method of Y. Tamaru et al. (Tetrahedron Lett. 1985, 26 (45), 5529). That is, a solution of Zn—Cu couple (4.6 g) and 1-chloro-4-iodobutane (10.0 g) in toluene (60 ml) and dimethylformamide (6 ml) was stirred at 60 ° C. for 3 hours in a nitrogen atmosphere. Next, a suspension of 2-methyl-1,3-dioxo-5-isoindolinecarbonyl chloride (6.82 g) and tetrakistriphenylphosphine palladium (1.4 g) obtained in Reference Example 230 in toluene (30 ml) was added to the previous solution. At room temperature. After stirring at room temperature for 1 hour, the reaction was quenched with water, and the solvent was distilled off under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate, and washed successively with 1N hydrochloric acid, water, aqueous potassium carbonate, water, and saturated brine. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as colorless crystals (5.15 g) having a melting point of 97-98 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.65-1.90 (4H, m), 3.06 (3H, s), 3.22 (2H, t, J = 6.8 Hz), 3.71 (2H, t, J = 6.2 Hz ), 7.98 (1H, d, J = 7.6 Hz), 8.25-8.40 (2H, m).

Reference Example 232

N-(2,3-ジヒドロ-1H-インデン-2-イル)アセトアミドおよび5-クロロバレリルクロリドを用い、参考例１と同様の操作を行うことにより、表題化合物を融点106-108℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.75 (4H, m), 1.79 (3H, s), 2.77 (2H, dd, J = 10.8, 3.0 Hz), 3.04 (2H, t, J = 6.6 Hz), 3.21 (2H, dd, J = 11.2, 5.2 Hz), 3.69 (2H, t, J = 6.3 Hz), 4.46 (1H, m), 7.35 (1H, d, J = 7.6 Hz), 7.80 (2H, m), 8.16 (1H, d, J = 5.4 Hz). N- [5- (5-Chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide

The title compound was purified in the same manner as in Reference Example 1 using N- (2,3-dihydro-1H-inden-2-yl) acetamide and 5-chlorovaleryl chloride to give a colorless compound having a melting point of 106-108 ° C. Obtained as crystals.
^{1 H NMR (200MHz, DMSO-} d 6) δ 1.75 (4H, m), 1.79 (3H, s), 2.77 (2H, dd, J = 10.8, 3.0 Hz), 3.04 (2H, t, J = 6.6 Hz ), 3.21 (2H, dd, J = 11.2, 5.2 Hz), 3.69 (2H, t, J = 6.3 Hz), 4.46 (1H, m), 7.35 (1H, d, J = 7.6 Hz), 7.80 (2H , m), 8.16 (1H, d, J = 5.4 Hz).

Reference Example 233

N-(2,3-ジヒドロ-1H-インデン-2-イル)メタンスルホンアミドおよび5-クロロバレリルクロリドを用い、参考例１と同様の操作を行うことにより、表題化合物を融点71-72℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.86 (4H, m), 2.96 (4H, m), 3.01 (3H, s), 3.35 (2H, dd, J = 10.8, 4.6 Hz), 3.58 (2H, t, J = 4.2 Hz), 4.29 (1H, m), 5.21 (1H, m), 7.27 (1H, d, J = 5.4 Hz), 7.79 (2H, m). N- [5- (5-Chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide

By performing the same operation as in Reference Example 1 using N- (2,3-dihydro-1H-inden-2-yl) methanesulfonamide and 5-chlorovaleryl chloride, the title compound was melted at 71-72 ° C. As colorless crystals.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.86 (4H, m), 2.96 (4H, m), 3.01 (3H, s), 3.35 (2H, dd, J = 10.8, 4.6 Hz), 3.58 (2H , t, J = 4.2 Hz), 4.29 (1H, m), 5.21 (1H, m), 7.27 (1H, d, J = 5.4 Hz), 7.79 (2H, m).

Reference Example 234

1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン25.00 gを アセトニトリル 250 mL に溶解し、5-クロロバレリルクロリド 25.9 mL (1.3 当量)、塩化亜鉛 4.20 g (0.2 当量)を添加した。80℃で 6 時間撹拌後、反応液を減圧濃縮した。酢酸エチル 250 mL、水 250 mL を添加して分液した。有機層を 水 125 mL で 2 回洗浄後、減圧濃縮して淡黄褐色結晶 53.16 gを得た。エタノール 125 mL を添加し、55℃に加温して結晶を溶解させた。ジイソプロピルエーテル 375 mL を滴下して結晶化させ、25℃まで冷却後、同温度で 1 時間撹拌した。5℃以下に冷却して 1 時間攪拌後、結晶をろ取した。冷エタノール-ジイソプロピルエーテル(1:3) 125 mL で結晶を洗浄し、減圧乾燥して微黄褐色結晶として表題化合物を27.16 gを得た。 5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one (compound of Reference Example 10)

Dissolve 25.00 g of 1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one in 250 mL of acetonitrile, 25.9 mL (1.3 eq) of 5-chlorovaleryl chloride, 4.20 g (0.2 eq) of zinc chloride ) Was added. After stirring at 80 ° C. for 6 hours, the reaction solution was concentrated under reduced pressure. 250 mL of ethyl acetate and 250 mL of water were added for liquid separation. The organic layer was washed twice with 125 mL of water and concentrated under reduced pressure to obtain 53.16 g of pale tan crystals. 125 mL of ethanol was added and heated to 55 ° C. to dissolve the crystals. 375 mL of diisopropyl ether was added dropwise to crystallize, cooled to 25 ° C., and stirred at the same temperature for 1 hour. After cooling to 5 ° C. or lower and stirring for 1 hour, the crystals were collected by filtration. The crystals were washed with 125 mL of cold ethanol-diisopropyl ether (1: 3) and dried under reduced pressure to obtain 27.16 g of the title compound as slightly tan crystals.

Reference Example 235

参考例６０で得た2-(2-クロロフェニル)エチル[5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(1.25g) のメタノール溶液(10ml)に、室温下テトラヒドロホウ酸ナトリウム95mgを加えた。室温下2時間撹拌した後、飽和塩化アンモニウム水溶液20mlを加えた。遊離した油状物をクロロホルム(30ml×2)で抽出し硫酸マグネシウムで乾燥したのち、溶媒を減圧下に留去して、表題化合物を淡黄色油状物(1.25g)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.21-1.52 (4H, m), 1.40 (9H, s), 1.63-1.90 (2H, m), 2.92 (2H, br.s), 3.08-3.23 (2H, m), 3.31-3.41 (2H, m), 3.36 (6H, s), 4.68 (1H, br.s), 5.10-5.18 (1H, m), 6.85 (1H, d, J = 8.1Hz), 6.96 (1H, m), 7.02 (1H, d, J = 8.1Hz), 7.16-7.34 (4H, m). 2- (2-Chlorophenyl) ethyl [5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-hydroxypentyl] carbamate tert-butyl

2- (2-Chlorophenyl) ethyl [5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamine obtained in Reference Example 60 To a methanol solution (10 ml) of tert-butyl acid (1.25 g), 95 mg of sodium tetrahydroborate was added at room temperature. After stirring at room temperature for 2 hours, 20 ml of a saturated aqueous ammonium chloride solution was added. The liberated oil was extracted with chloroform (30 ml × 2) and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the title compound as a pale yellow oil (1.25 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.21-1.52 (4H, m), 1.40 (9H, s), 1.63-1.90 (2H, m), 2.92 (2H, br.s), 3.08-3.23 (2H, m), 3.31-3.41 (2H, m), 3.36 (6H, s), 4.68 (1H, br.s), 5.10-5.18 (1H, m), 6.85 (1H, d, J = 8.1Hz), 6.96 (1H, m), 7.02 (1H, d, J = 8.1Hz), 7.16-7.34 (4H, m).

Reference Example 236

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(584mg) および4-(2-アミノエチル)-3-クロロフェノール 臭化水素酸塩(1.1g) を用いて、参考例８２と同様の操作を行うことにより、表題化合物を淡黄色油状物(250mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.72 (2H, t, J = 7.5Hz), 2.85 (2H, br.s), 2.92 (2H, t, J = 6.8Hz), 3.01 (2H, t, J = 7.5Hz), 3.15-3.24 (4H, m), 3.36 (2H, br.s), 4.13 (2H, t, J = 8.3Hz), 6.69 (1H, d, J = 7.0Hz), 6.89-7.07 (3H, m), 7.66 (1H, s), 7.71 (1H, s). 2- (2-Chloro-4-hydroxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-8 -Yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (584 mg) obtained in Reference Example 1 and 4- ( The title compound was obtained as a pale-yellow oil (250 mg) by the same procedures as in Reference Example 82 using 2-aminoethyl) -3-chlorophenol hydrobromide (1.1 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.73 (4H, m), 2.72 (2H, t, J = 7.5Hz), 2.85 (2H, br.s), 2.92 (2H , t, J = 6.8Hz), 3.01 (2H, t, J = 7.5Hz), 3.15-3.24 (4H, m), 3.36 (2H, br.s), 4.13 (2H, t, J = 8.3Hz) , 6.69 (1H, d, J = 7.0Hz), 6.89-7.07 (3H, m), 7.66 (1H, s), 7.71 (1H, s).

Reference Example 237

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オン(560mg)および4-(2-アミノエチル)-3-クロロフェノール 臭化水素酸塩(1.1g) を用いて、参考例８２と同様の操作を行うことにより、表題化合物を淡黄色油状物(320mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.41 (9H, s), 1.51-1.72 (4H, m), 2.26 (3H, s), 2.85 (2H, br.s), 2.95 (2H, t, J = 7.3Hz), 3.15 (2H, br.s), 3.23 (2H, t, J = 8.0Hz), 3.36 (2H, t, J = 7.0Hz), 4.11 (2H, t, J = 7.0Hz), 6.69 (1H, d, J = 6.3Hz), 6.90-7.07 (3H, m), 7.80 (1H, s), 7.81 (1H, d, J = 8.0Hz), 8.22 (1H, d, J = 8.0Hz). 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-chloro-4-hydroxyphenyl) ethyl] carbamate tert-butyl

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one (560 mg) and 4- (2-aminoethyl) -3 obtained in Reference Example 11 The title compound was obtained as a pale-yellow oil (320 mg) by the same procedures as in Reference Example 82 using chlorophenol hydrobromide (1.1 g).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.41 (9H, s), 1.51-1.72 (4H, m), 2.26 (3H, s), 2.85 (2H, br.s), 2.95 (2H, t, J = 7.3Hz), 3.15 (2H, br.s), 3.23 (2H, t, J = 8.0Hz), 3.36 (2H, t, J = 7.0Hz), 4.11 (2H, t, J = 7.0Hz), 6.69 (1H, d, J = 6.3Hz), 6.90-7.07 (3H, m), 7.80 (1H, s), 7.81 (1H, d, J = 8.0Hz), 8.22 (1H, d, J = 8.0Hz) .

Reference Example 238

参考例１３４で得た8-(5-クロロペンタノイル)-1-メチル-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オン(460mg)および4-(2-アミノエチル)-3-クロロフェノール 臭化水素酸塩(796mg) を用いて、参考例８２と同様の操作を行うことにより、表題化合物を淡黄色油状物(114mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.40 (9H, s), 1.60 (2H, br.s), 1.66-1.75 (2H, m), 2.10-2.16 (2H, m), 2.84-3.00 (6H, m), 3.16-3.22 (2H, m), 3.31-3.38 (2H, m), 3.45 (3H, s), 3.82-3.89 (2H,m), 6.70 (1H, d, J = 7.8Hz), 6.83-7.02 (2H, m), 7.23 (1H, br.), 7.49 (1H, s), 7.56 (1H, s). 2- (2-Chloro-4-hydroxyphenyl) ethyl [5- (1-methyl-2-oxo-1,2,5,6-tetrahydro-4H-imidazo [4,5,1-ij] quinoline-8 -Yl) -5-oxopentyl] carbamate tert-butyl

8- (5-Chloropentanoyl) -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one (460 mg) obtained in Reference Example 134 and The title compound was obtained as a pale-yellow oil (114 mg) by the same procedures as in Reference Example 82 using 4- (2-aminoethyl) -3-chlorophenol hydrobromide (796 mg). .
¹ H NMR (400MHz, CDCl ₃ ) δ 1.40 (9H, s), 1.60 (2H, br.s), 1.66-1.75 (2H, m), 2.10-2.16 (2H, m), 2.84-3.00 (6H, m), 3.16-3.22 (2H, m), 3.31-3.38 (2H, m), 3.45 (3H, s), 3.82-3.89 (2H, m), 6.70 (1H, d, J = 7.8Hz), 6.83 -7.02 (2H, m), 7.23 (1H, br.), 7.49 (1H, s), 7.56 (1H, s).

Reference Example 239

参考例１３３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オン(439mg)および4-(2-アミノエチル)-3-クロロフェノール 臭化水素酸塩(796mg) を用いて、参考例８２と同様の操作を行うことにより、表題化合物を淡黄色油状物(55mg)として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (9H, s), 1.49-1.72 (4H, m), 2.13 (2H, br.s), 2.83-2.89 (6H, m), 3.08 (2H, br.s), 3.35 (2H, t, J = 6.8Hz), 3.88 (2H, br.s), 6.88-7.02 (3H, m), 7.51 (1H, s), 7.56 (1H, br.s), 8.09 (1H, br), 9.95 (1H, s). 2- (2-Chloro-4-hydroxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-imidazo [4,5,1-ij] quinoline-8 -Yl) pentyl] carbamic acid tert-butyl

8- (5-Chloropentanoyl) -5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one (439 mg) and 4- (2) obtained in Reference Example 133 The title compound was obtained as a pale yellow oil (55 mg) by the same procedures as in Reference Example 82 using -aminoethyl) -3-chlorophenol hydrobromide (796 mg).
¹ H NMR (400MHz, CDCl ₃ ) δ 1.43 (9H, s), 1.49-1.72 (4H, m), 2.13 (2H, br.s), 2.83-2.89 (6H, m), 3.08 (2H, br. s), 3.35 (2H, t, J = 6.8Hz), 3.88 (2H, br.s), 6.88-7.02 (3H, m), 7.51 (1H, s), 7.56 (1H, br.s), 8.09 (1H, br), 9.95 (1H, s).

Reference Example 240

参考例１３１で得た5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンを用いて、参考例１および参考例８２と同様の操作を行うことにより、表題化合物を淡黄色油状物として得た。
¹H NMR (400MHz, CDCl₃) δ 1.43 (9H, s), 1.56 (2H, br.s), 1.68 (2H, br.s), 2.09-2.16 (2H, m), 2.84-2.90 (4H, m), 2.95 (2H, t, J = 7.0Hz), 3.13 (2H, t, J = 7.3Hz), 3.35 (2H, t, J = 7.0Hz), 3.87 (2H, t, J = 6.0Hz), 6.88-7.04 (4H, m), 7.44 (1H, d, J = 8.0Hz), 7.89 (1H, br.), 9.34 (1H, s). 2- (2-Chloro-4-hydroxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-imidazo [4,5,1-ij] quinoline-9 -Yl) pentyl] carbamic acid tert-butyl

Perform the same operations as in Reference Example 1 and Reference Example 82 using 5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one obtained in Reference Example 131. Gave the title compound as a pale yellow oil.
_{^{1 H NMR (400MHz, CDCl 3}} ) δ 1.43 (9H, s), 1.56 (2H, br.s), 1.68 (2H, br.s), 2.09-2.16 (2H, m), 2.84-2.90 (4H, m), 2.95 (2H, t, J = 7.0Hz), 3.13 (2H, t, J = 7.3Hz), 3.35 (2H, t, J = 7.0Hz), 3.87 (2H, t, J = 6.0Hz) , 6.88-7.04 (4H, m), 7.44 (1H, d, J = 8.0Hz), 7.89 (1H, br.), 9.34 (1H, s).

Reference Example 241

N-(2,3-ジヒドロ-1H-インデン-2-イル)-N-メチルアセトアミドおよび5-クロロバレリルクロリドを用い、実施例１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
¹H NMR (200MHz, CDCl₃) δ 1.81 (4H, m), 2.20 (3H, s), 2.41 (2H, m), 2.79 (3H, s), 3.06 (2H, t, J = 6.6 Hz), 3.18-3.22 (2H, m), 3.59 (2H, t, J = 6.3 Hz), 5.46 (1H, m), 7.30 (1H, m), 7.81 (2H, m). N- [5- (5-Chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide

The title compound was obtained as colorless crystals by performing the same operation as in Example 1 using N- (2,3-dihydro-1H-inden-2-yl) -N-methylacetamide and 5-chlorovaleryl chloride. Obtained.
¹ H NMR (200MHz, CDCl ₃ ) δ 1.81 (4H, m), 2.20 (3H, s), 2.41 (2H, m), 2.79 (3H, s), 3.06 (2H, t, J = 6.6 Hz), 3.18-3.22 (2H, m), 3.59 (2H, t, J = 6.3 Hz), 5.46 (1H, m), 7.30 (1H, m), 7.81 (2H, m).

Reference Example 242

N-(2,3-ジヒドロ-1H-インデン-2-イル)メタンスルホンアミドおよび5-クロロバレリルクロリドを用い、実施例１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
MS m/z: 344 [M+H]⁺ N- [5- (5-Chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide

The title compound was obtained as colorless crystals by performing the same operation as in Example 1 using N- (2,3-dihydro-1H-inden-2-yl) methanesulfonamide and 5-chlorovaleryl chloride. .
MS m / z: 344 [M + H] +

参考例１９で得た5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(3.00g) のエタノール(5ml) 溶液に４規定塩化水素−酢酸エチル溶液(15ml) を加え、室温で1時間攪拌した。溶媒を減圧下留去し、得られた残渣をエタノール−酢酸エチルから結晶化させることにより、表題化合物を融点166-168 ℃の無色結晶(1.98g)として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.60-1.75 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.90-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.20-7.40 (5H, m), 7.73 (1H, s), 7.74 (1H, s), 8.95-9.10 (2H, br).
元素分析 C₂₄H₂₈N₂O₂・HClとして
計算値：C, 69.80; H, 7.08; N, 6.78.
実験値：C, 69.43; H, 7.06; N, 6.72. 8- [5-[(2-Phenylethyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl (2-phenyl) obtained in Reference Example 19 To a solution of tert-butyl ethyl) carbamate (3.00 g) in ethanol (5 ml) was added 4N hydrogen chloride-ethyl acetate solution (15 ml), and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, and the obtained residue was crystallized from ethanol-ethyl acetate to give the title compound as colorless crystals (1.98 g) having a melting point of 166-168 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.75 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.90-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.20-7.40 (5H, m), 7.73 (1H, s), 7.74 (1H, s), 8.95-9.10 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₂₈ N ₂ O ₂ .HCl: C, 69.80; H, 7.08; N, 6.78.
Experimental value: C, 69.43; H, 7.06; N, 6.72.

参考例２０で得た2-(2-メトキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸
tert-ブチル(1.16g) を用いて、実施例１と同様の操作を行うことにより、表題化合物(835mg) を融点94-96℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.15 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.91 (1H, dt, J = 7.3, 1.0Hz), 7.00 (1H, d, J = 7.6Hz), 7.15-7.30 (2H, m), 7.74 (2H, s), 8.95-9.15 (2H, br).
元素分析 C₂₅H₃₀N₂O₃・HCl・H₂O として
計算値：C, 62.69; H, 7.36; N, 5.85.
実験値：C, 63.02; H, 7.15; N, 5.82. 8- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (2-Methoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 20 -8-yl) pentyl] carbamic acid
The same operation as in Example 1 was carried out using tert-butyl (1.16 g) to give the title compound (835 mg) as colorless crystals having a melting point of 94-96 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.15 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.91 (1H, dt, J = 7.3, 1.0Hz), 7.00 (1H, d, J = 7.6Hz), 7.15 -7.30 (2H, m), 7.74 (2H, s), 8.95-9.15 (2H, br).
Elemental analysis _{C 25 H 30 N 2 O 3} · HCl · H 2 O Calculated: C, 62.69; H, 7.36 ; N, 5.85.
Experimental values: C, 63.02; H, 7.15; N, 5.82.

参考例２１で得た2-(3-メトキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(3.02g) を用いて、実施例１と同様の操作を行うことにより、表題化合物(2.32g) を融点97-100℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.20 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.75 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.75-6.85 (3H, m), 7.25 (1H, t, J = 8.2 Hz), 7.74 (2H, s), 9.15-9.35 (2H, br).
元素分析 C₂₅H₃₀N₂O₃・HCl・1.5H₂O として
計算値：C, 63.89; H, 7.29; N, 5.96.
実験値：C, 64.01; H, 7.01; N, 6.01. 8- (5-[[2- (3-Methoxyphenyl) ethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (3-Methoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 21 -8-yl) pentyl] carbamate tert-butyl (3.02 g) was used for the same procedure as in Example 1 to obtain the title compound (2.32 g) as colorless crystals having a melting point of 97-100 ° C. .
^{1 H NMR (200MHz, DMSO-} d 6) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.20 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.75 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.75-6.85 (3H, m), 7.25 (1H, t, J = 8.2 Hz), 7.74 (2H, s) , 9.15-9.35 (2H, br).
Elemental analysis _{C 25 H 30 N 2 O 3} · HCl · 1.5H 2 O Calculated: C, 63.89; H, 7.29 ; N, 5.96.
Experimental value: C, 64.01; H, 7.01; N, 6.01.

参考例２２で得た2-(3,4-ジメトキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(408mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(290mg) を融点175-176℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.72 (3H, s), 3.75 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.76 (1H, dd, J = 8.2, 1.8Hz), 6.90 (2H, d, J = 8.2Hz), 7.73 (2H, s), 8.85-9.05 (2H, br). 8- (5-[[2- (3,4-Dimethoxyphenyl) ethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

2- (3,4-Dimethoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] obtained in Reference Example 22 The title compound (290 mg) was obtained as colorless crystals having a melting point of 175 to 176 ° C. by performing the same operation as in Example 1 using [quinolin-8-yl) pentyl] carbamate tert-butyl (408 mg). .
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.72 (3H, s), 3.75 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.76 (1H, dd, J = 8.2, 1.8Hz), 6.90 (2H, d, J = 8.2Hz), 7.73 (2H, s), 8.85-9.05 (2H, br).

参考例２３で得た2-(2-クロロフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(1.50g) を用いて、実施例１と同様の操作を行うことにより、表題化合物(989mg) を融点128-130℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.90-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.00-7.55 (4H, m), 7.73 (2H, s), 9.10-9.30 (2H, br).
元素分析 C₂₄H₂₇ClN₂O₂・HCl・H₂O として
計算値：C, 60.76; H, 6.59; N, 5.90.
実験値：C, 61.15; H, 6.20; N, 5.77. 8- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

2- (2-Chlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- obtained in Reference Example 23 The title compound (989 mg) was obtained as colorless crystals with a melting point of 128-130 ° C. by the same procedure as in Example 1 using 8-yl) pentyl] carbamate tert-butyl (1.50 g).
^{1 H NMR (200MHz, DMSO-} d 6) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.90-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.00-7.55 (4H, m), 7.73 (2H, s), 9.10-9.30 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ · HCl · H ₂ O: C, 60.76; H, 6.59; N, 5.90.
Experimental values: C, 61.15; H, 6.20; N, 5.77.

参考例２４で得た2-(3-フルオロフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(1.40g) を用いて、実施例１と同様の操作を行うことにより、表題化合物(905mg) を融点172-173℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.00-7.20 (3H, m), 7.50-7.65 (1H, m), 7.74 (2H, s), 8.90-9.10 (2H, br).
元素分析 C₂₄H₂₇FN₂O₂・HClとして
計算値：C, 66.89; H, 6.55; N, 6.50.
実験値：C, 66.50; H, 6.21; N, 6.20. 8- (5-[[2- (3-Fluorophenyl) ethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (3-Fluorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 24 The title compound (905 mg) was obtained as colorless crystals having a melting point of 172-173 ° C. by performing the same operation as in Example 1 using -8-yl) pentyl] carbamate tert-butyl (1.40 g).
^{1 H NMR (200MHz, DMSO-} d 6) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.00-7.20 (3H, m), 7.50-7.65 (1H, m), 7.74 (2H, s), 8.90-9.10 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₂₇ FN ₂ O ₂ .HCl: C, 66.89; H, 6.55; N, 6.50.
Experimental value: C, 66.50; H, 6.21; N, 6.20.

参考例２５で得た2-[3-(アミノスルホニル)-4-メトキシフェニル]エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(605mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(325mg) を融点145℃(分解)の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.55-1.75 (4H, m), 2.60 (2H, t, J = 7.6Hz), 2.85-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.89 (3H, s), 3.99 (2H, t, J = 8.4Hz), 7.08 (2H, s), 7.18 (1H, d, J = 8.8Hz), 7.47 (1H, dd, J = 8.6, 2.2Hz), 7.63 (1H, d, J = 2.2Hz), 7.74 (2H, s), 8.85-9.05 (2H, br).
元素分析 C₂₅H₃₁N₃O₅S・HCl・H₂O として
計算値：C, 55.60; H, 6.35; N, 7.78.
実験値：C, 55.51; H, 6.50; N, 7.46. 2-Methoxy-5- (2-[[5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) Pentyl] amino] ethyl) benzenesulfonamide hydrochloride

2- [3- (Aminosulfonyl) -4-methoxyphenyl] ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3, 2,1-ij] Quinolin-8-yl) pentyl] carbamate tert-butyl (605 mg) was used in the same manner as in Example 1 to obtain the title compound (325 mg) with a melting point of 145 ° C. (decomposition). As colorless crystals.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.55-1.75 (4H, m), 2.60 (2H, t, J = 7.6Hz), 2.85-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.89 (3H, s), 3.99 (2H, t, J = 8.4Hz), 7.08 (2H, s), 7.18 (1H, d, J = 8.8Hz), 7.47 (1H, dd, J = 8.6, 2.2Hz), 7.63 (1H, d, J = 2.2Hz), 7.74 (2H, s), 8.85-9.05 (2H, br).
Elemental analysis Calculated as C ₂₅ H ₃₁ N ₃ O ₅ S · HCl · H ₂ O: C, 55.60; H, 6.35; N, 7.78.
Experimental values: C, 55.51; H, 6.50; N, 7.46.

参考例２６で得た2-(2-メトキシフェニル)-1-メチルエチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(641mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(438mg) を淡黄色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.10 (3H, d, J = 6.2Hz), 1.60-1.90 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.20 (9H, m), 3.18 (2H, t, J = 8.4Hz), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.80-7.60 (4H, m), 7.73 (2H, s), 8.90-9.25 (2H, br).
元素分析 C₂₆H₃₂N₂O₃・HCl・H₂O として
計算値：C, 65.74; H, 7.43; N, 5.90.
実験値：C, 65.44; H, 7.09; N, 5.72. 8- (5-[[2- (2-methoxyphenyl) -1-methylethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- 4-one hydrochloride

2- (2-methoxyphenyl) -1-methylethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1] obtained in Reference Example 26 -ij] Quinolin-8-yl) pentyl] carbamate tert-butyl (641 mg) was used for the same operation as in Example 1 to obtain the title compound (438 mg) as a pale yellow amorphous powder. .
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.10 (3H, d, J = 6.2Hz), 1.60-1.90 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.20 (9H , m), 3.18 (2H, t, J = 8.4Hz), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.80-7.60 (4H, m), 7.73 (2H, s) , 8.90-9.25 (2H, br).
Elemental analysis Calculated as C ₂₆ H ₃₂ N ₂ O ₃ .HCl.H ₂ O: C, 65.74; H, 7.43; N, 5.90.
Experimental value: C, 65.44; H, 7.09; N, 5.72.

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(800mg)、N-メチル-N-(2-フェニルエチル)アミン(0.438ml)および炭酸カリウム(830mg) のトルエン(10ml) 混合液を攪拌しながら12時間加熱還流した。冷却後、反応液に水(15ml)および酢酸エチル(20ml)を加え、酢酸エチルで抽出した。抽出液を、飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル)にて精製し、表題化合物のフリー塩基体を淡黄色油状物(519mg)として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.50-1.65 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.31 (3H, s), 2.45 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.92 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 8.1Hz), 3.21 (2H, t, J = 8.1Hz), 4.12 (2H, t, J = 8.4Hz), 7.15-7.30 (5H, m), 7.67 (1H, s), 7.72 (1H, s).
上記フリー塩基体(519mg) のエタノール溶液を１当量以上の塩化水素（酢酸エチル溶液）で処理し、表題化合物を淡黄色非晶状粉末(539mg) として得た。
元素分析 C₂₅H₃₀N₂O₂・HClとして
計算値：C, 70.32; H, 7.32; N, 6.56.
実験値：C, 70.04; H, 7.56; N, 6.59. 8- [5- [Methyl (2-phenylethyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (800 mg), N-methyl obtained in Reference Example 1 A mixture of -N- (2-phenylethyl) amine (0.438 ml) and potassium carbonate (830 mg) in toluene (10 ml) was heated to reflux with stirring for 12 hours. After cooling, water (15 ml) and ethyl acetate (20 ml) were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; ethyl acetate) to give the free base of the title compound as a pale yellow oil (519 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.50-1.65 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.31 (3H, s), 2.45 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.92 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 8.1Hz), 3.21 (2H , t, J = 8.1Hz), 4.12 (2H, t, J = 8.4Hz), 7.15-7.30 (5H, m), 7.67 (1H, s), 7.72 (1H, s).
The ethanol solution of the above free base (519 mg) was treated with 1 equivalent or more of hydrogen chloride (ethyl acetate solution) to obtain the title compound as a pale yellow amorphous powder (539 mg).
Elemental analysis Calculated as C ₂₅ H ₃₀ N ₂ O ₂ .HCl: C, 70.32; H, 7.32; N, 6.56.
Experimental value: C, 70.04; H, 7.56; N, 6.59.

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(322mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(280mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.50-1.65 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.32 (3H, s), 2.47 (2H, t, J = 7.5Hz), 2.50-2.60 (2H, m), 2.65-2.80 (4H, m), 2.93 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 8.1Hz), 3.22 (2H, t, J = 8.1Hz), 3.81 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.84 (1H, d, J = 7.5Hz), 6.88 (1H, d, J = 7.8Hz), 7.10-7.20 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₆H₃₂N₂O₃・HCl・0.5H₂O として
計算値：C, 67.01; H, 7.35; N, 6.01.
実験値：C, 67.03; H, 7.68; N, 5.97. 8- [5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 1 and N- [ The title compound (280 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-methoxyphenyl) ethyl] -N-methylamine (322 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.50-1.65 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.32 (3H, s), 2.47 (2H, t, J = 7.5Hz), 2.50-2.60 (2H, m), 2.65-2.80 (4H, m), 2.93 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 8.1Hz), 3.22 (2H , t, J = 8.1Hz), 3.81 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.84 (1H, d, J = 7.5Hz), 6.88 (1H, d, J = 7.8Hz ), 7.10-7.20 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₆ H ₃₂ N ₂ O ₃ · HCl · 0.5H ₂ O: C, 67.01; H, 7.35; N, 6.01.
Experimental values: C, 67.03; H, 7.68; N, 5.97.

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(3-メトキシフェニル)エチル]-N-メチルアミン(322mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(160mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.50-1.65 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.30 (3H, s), 2.45 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.92 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.21 (2H, t, J = 8.1Hz), 3.78 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.70-6.80 (3H, m), 7.16 (1H, t, J = 7.8Hz), 7.67 (1H, s), 7.72 (1H, s). 8- [5-[[2- (3-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 1 and N- [ The title compound (160 mg) was obtained as a pale yellow amorphous powder by the same operation as in Example 9 using 2- (3-methoxyphenyl) ethyl] -N-methylamine (322 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.50-1.65 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.30 (3H, s), 2.45 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.92 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.21 (2H , t, J = 8.1Hz), 3.78 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.70-6.80 (3H, m), 7.16 (1H, t, J = 7.8Hz), 7.67 (1H, s), 7.72 (1H, s).

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(330mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(310mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.50-1.65 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.34 (3H, s), 2.47 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.85-2.95 (4H, m), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.1Hz), 4.13 (2H, t, J = 8.4Hz), 7.05-7.35 (4H, m), 7.68 (1H, s), 7.72 (1H, s). 8- [5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 1 and N- [ The title compound (310 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-chlorophenyl) ethyl] -N-methylamine (330 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.50-1.65 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.34 (3H, s), 2.47 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.85-2.95 (4H, m), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H , t, J = 8.1Hz), 4.13 (2H, t, J = 8.4Hz), 7.05-7.35 (4H, m), 7.68 (1H, s), 7.72 (1H, s).

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(3-クロロフェニル)エチル]-N-メチルアミン(345mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(298mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.50-1.65 (2H, m), 1.73 (2H, tt, J = 7.4, 7.4Hz), 2.29 (3H, s), 2.44 (2H, t, J = 7.4Hz), 2.50-2.80 (6H, m), 2.92 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₅H₂₉ClN₂O₂・HCl・H₂Oとして
計算値：C, 62.63; H, 6.73; N, 5.84.
実験値：C, 62.51; H, 6.53; N, 5.70. 8- [5-[[2- (3-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 1 and N- [ The title compound (298 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2- (3-chlorophenyl) ethyl] -N-methylamine (345 mg).
¹ H NMR (free _{base; 200MHz, CDCl 3) δ 1.50-1.65} (2H, m), 1.73 (2H, tt, J = 7.4, 7.4Hz), 2.29 (3H, s), 2.44 (2H, t, J = 7.4Hz), 2.50-2.80 (6H, m), 2.92 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis Calculated as C ₂₅ H ₂₉ ClN ₂ O ₂ · HCl · H ₂ O: C, 62.63; H, 6.73; N, 5.84.
Experimental value: C, 62.51; H, 6.53; N, 5.70.

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミン(276mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(340mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.50-1.65 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.29 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.92 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.1Hz), 4.12 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m), 7.15-7.25 (1H, m), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₅H₂₉FN₂O₂・HCl・0.5H₂Oとして
計算値：C, 66.14; H, 6.88; N, 6.17.
実験値：C, 66.23; H, 6.38; N, 5.74. 8- [5-[[2- (3-Fluorophenyl) ethyl] (methyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 1 and N- [ The title compound (340 mg) was obtained as a pale yellow amorphous powder by the same procedure as in Example 9 using 2- (3-fluorophenyl) ethyl] -N-methylamine (276 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.50-1.65 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.29 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.92 (2H, t, J = 7.5Hz), 3.01 (2H, t, J = 7.8Hz), 3.22 (2H , t, J = 8.1Hz), 4.12 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m), 7.15-7.25 (1H, m), 7.67 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₅ H ₂₉ FN ₂ O ₂ · HCl · 0.5H ₂ O: C, 66.14; H, 6.88; N, 6.17.
Experimental values: C, 66.23; H, 6.38; N, 5.74.

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-エチル-N-(2-フェニルエチル)アミン(281mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(230mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.06 (3H, t, J = 7.2Hz), 1.56 (2H, tt, J = 7.5, 7.5Hz), 1.73 (2H, tt, J = 7.5, 7.5Hz), 2.50-2.80 (10H, m), 2.92 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.10-7.30 (5H, m), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₆H₃₂N₂O₂・HCl・0.5H₂Oとして
計算値：C, 69.39; H, 7.62; N, 6.23.
実験値：C, 69.50; H, 7.69; N, 6.17. 8- [5- [Ethyl (2-phenylethyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and N-ethyl obtained in Reference Example 1 Using the same procedure as in Example 9 using -N- (2-phenylethyl) amine (281 mg), the title compound (230 mg) was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.06 (3H, t, J = 7.2 Hz), 1.56 (2H, tt, J = 7.5, 7.5 Hz), 1.73 (2H, tt, J = 7.5, 7.5 Hz), 2.50-2.80 (10H, m), 2.92 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.12 ( 2H, t, J = 8.4Hz), 7.10-7.30 (5H, m), 7.67 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₆ H ₃₂ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 69.39; H, 7.62; N, 6.23.
Experimental value: C, 69.50; H, 7.69; N, 6.17.

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-エチル-N-[2-(2-メトキシフェニル)エチル]アミン(337mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(300mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.07 (3H, t, J = 7.2Hz), 1.35-1.45 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.50-2.80 (10H, m), 2.93 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.84 (1H, d, J = 8.1Hz), 6.88 (1H, d, J = 7.2Hz), 7.10-7.20 (2H, m), 7.68 (1H, s), 7.73 (1H, s).
元素分析 C₂₇H₃₄N₂O₃・HCl・H₂Oとして
計算値：C, 66.31; H, 7.63; N, 5.73.
実験値：C, 66.58; H, 7.36; N, 5.49. 8- (5- [Ethyl [2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and N-ethyl obtained in Reference Example 1 Using the same procedure as in Example 9 using -N- [2- (2-methoxyphenyl) ethyl] amine (337 mg), the title compound (300 mg) was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.07 (3H, t, J = 7.2 Hz), 1.35-1.45 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5 Hz), 2.50- 2.80 (10H, m), 2.93 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.84 (1H, d, J = 8.1Hz), 6.88 (1H, d, J = 7.2Hz), 7.10-7.20 (2H, m), 7.68 (1H, s ), 7.73 (1H, s).
Elemental analysis _{C 27 H 34 N 2 O 3} · HCl · H 2 O Calculated: C, 66.31; H, 7.63 ; N, 5.73.
Experimental values: C, 66.58; H, 7.36; N, 5.49.

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) およびN-イソプロピル-N-[2-(2-メトキシフェニル)エチル]アミン(510mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(310mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.00 (6H, d, J = 6.6Hz), 1.50-1.60 (2H, m), 1.74 (2H, tt, J = 7.4, 7.4Hz), 2.51 (2H, t, J = 7.5Hz), 2.55-3.05 (11H, m), 3.22 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.95 (2H, m), 7.10-7.20 (2H, m), 7.69 (1H, s), 7.73 (1H, s). 8- (5- [Isopropyl [2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) and N-isopropyl obtained in Reference Example 1 Using the same procedure as in Example 9 using -N- [2- (2-methoxyphenyl) ethyl] amine (510 mg), the title compound (310 mg) was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.00 (6H, d, J = 6.6Hz), 1.50-1.60 (2H, m), 1.74 (2H, tt, J = 7.4, 7.4Hz), 2.51 ( 2H, t, J = 7.5Hz), 2.55-3.05 (11H, m), 3.22 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.95 (2H, m), 7.10-7.20 (2H, m), 7.69 (1H, s), 7.73 (1H, s).

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) およびN-[2-(2-クロロフェニル)エチル]-N-イソプロピルアミン (522mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(70mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.00 (6H, d, J = 6.6Hz), 1.50-1.60 (2H, m), 1.73 (2H, tt, J = 7.4, 7.4Hz), 2.51 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.80-3.05 (5H, m), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.05-7.40 (4H, m), 7.68 (1H, s), 7.72 (1H, s). 8- [5-[[2- (2-Chlorophenyl) ethyl] (isopropyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) obtained in Reference Example 1 and N- [ The title compound (70 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-chlorophenyl) ethyl] -N-isopropylamine (522 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.00 (6H, d, J = 6.6Hz), 1.50-1.60 (2H, m), 1.73 (2H, tt, J = 7.4, 7.4Hz), 2.51 ( 2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.80-3.05 (5H, m), 3.22 (2H, t, J = 8.4Hz ), 4.13 (2H, t, J = 8.4Hz), 7.05-7.40 (4H, m), 7.68 (1H, s), 7.72 (1H, s).

参考例２７で得た6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル(2-フェニルエチル)カルバミン酸 tert-ブチル (450mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(283mg) を融点144-146℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.20-7.40 (5H, m), 7.73 (2H, s), 8.90-9.10 (2H, br). 8- [6-[(2-Phenylethyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

6-Oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl (2-phenyl) obtained in Reference Example 27 The title compound (283 mg) was obtained as colorless crystals having a melting point of 144-146 ° C. by carrying out the same operation as in Example 1 using tert-butyl (ethyl) carbamate (450 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.25 (12H, m) , 3.99 (2H, t, J = 8.4Hz), 7.20-7.40 (5H, m), 7.73 (2H, s), 8.90-9.10 (2H, br).

参考例２８で得た2-(2-メトキシフェニル)エチル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸 tert-ブチル (1.51g) を用いて、実施例１と同様の操作を行うことにより、表題化合物(1.04g) を融点105-107℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.10 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.91 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 8.4Hz), 7.15-7.30 (2H, m), 7.73 (2H, s), 8.75-9.00 (2H, br).
元素分析 C₂₆H₃₂N₂O₃・HCl・H₂Oとして
計算値：C, 65.74; H, 7.43; N, 5.90.
実験値：C, 66.09; H, 7.01; N, 5.80. 8- (6-[[2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (2-Methoxyphenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 28 -8-yl) hexyl] carbamate tert-butyl (1.51 g) was used for the same operation as in Example 1 to obtain the title compound (1.04 g) as colorless crystals having a melting point of 105-107 ° C. .
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.10 (10H, m) , 3.17 (2H, t, J = 8.4Hz), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.91 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 8.4Hz), 7.15-7.30 (2H, m), 7.73 (2H, s), 8.75-9.00 (2H, br).
Elemental analysis Calculated as C ₂₆ H ₃₂ N ₂ O ₃ .HCl.H ₂ O: C, 65.74; H, 7.43; N, 5.90.
Experimental value: C, 66.09; H, 7.01; N, 5.80.

参考例２９で得た2-(3-メトキシフェニル)エチル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸 tert-ブチル (562mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(435mg) を融点136-138℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m), 3.75 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.80-6.85 (3H, m), 7.25 (1H, t, J = 7.8Hz), 7.73 (2H, s), 9.00-9.20 (2H, br).
元素分析 C₂₆H₃₂N₂O₃・HCl・H₂Oとして
計算値：C, 65.74; H, 7.43; N, 5.90.
実験値：C, 65.54; H, 7.28; N, 5.80. 8- (6-[[2- (3-Methoxyphenyl) ethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (3-Methoxyphenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 29 The title compound (435 mg) was obtained as colorless crystals with a melting point of 136-138 ° C. by the same procedure as in Example 1 using -8-yl) hexyl] carbamate tert-butyl (562 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m) , 3.75 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.80-6.85 (3H, m), 7.25 (1H, t, J = 7.8Hz), 7.73 (2H, s), 9.00- 9.20 (2H, br).
Elemental analysis Calculated as C ₂₆ H ₃₂ N ₂ O ₃ .HCl.H ₂ O: C, 65.74; H, 7.43; N, 5.90.
Experimental value: C, 65.54; H, 7.28; N, 5.80.

参考例３０で得た2-(4-メトキシフェニル)エチル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸 tert-ブチル (900mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(707mg) を融点179-180℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.25-1.45 (2H, m), 1.55-1.75 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.80-3.10 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.73 (3H, s), 3.98 (2H, t, J = 8.4Hz), 6.89 (2H, d, J = 7.5Hz), 7.18 (2H, d, J = 7.5Hz), 7.73 (2H, s), 8.90-9.10 (2H, br).
元素分析 C₂₆H₃₂N₂O₃・HCl・0.5H₂Oとして
計算値：C, 67.01; H, 7.35; N, 6.01.
実験値：C, 67.53; H, 7.40; N, 6.03. 8- (6-[[2- (4-Methoxyphenyl) ethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (4-Methoxyphenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 30 The title compound (707 mg) was obtained as colorless crystals with a melting point of 179-180 ° C. by the same procedure as in Example 1 using -8-yl) hexyl] carbamate tert-butyl (900 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.25-1.45 (2H, m), 1.55-1.75 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.80-3.10 (10H, m) , 3.17 (2H, t, J = 8.4Hz), 3.73 (3H, s), 3.98 (2H, t, J = 8.4Hz), 6.89 (2H, d, J = 7.5Hz), 7.18 (2H, d, J = 7.5Hz), 7.73 (2H, s), 8.90-9.10 (2H, br).
Elemental analysis _{C 26 H 32 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 67.01; H, 7.35 ; N, 6.01.
Experimental values: C, 67.53; H, 7.40; N, 6.03.

参考例３１で得た2-(2-クロロフェニル)エチル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸 tert-ブチル(540mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(368mg) を融点172-174℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.25-7.50 (4H, m), 7.73 (2H, s), 9.05-9.30 (2H, br).
元素分析 C₂₅H₂₉ClN₂O₂・HCl・0.5H₂Oとして
計算値：C, 63.83; H, 6.64; N, 5.95.
実験値：C, 63.68; H, 6.57; N, 5.80. 8- (6-[[2- (2-Chlorophenyl) ethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

2- (2-Chlorophenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- obtained in Reference Example 31 The title compound (368 mg) was obtained as colorless crystals having a melting point of 172-174 ° C. by performing the same operation as in Example 1 using 8-yl) hexyl] carbamate tert-butyl (540 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m) , 3.99 (2H, t, J = 8.4Hz), 7.25-7.50 (4H, m), 7.73 (2H, s), 9.05-9.30 (2H, br).
Elemental analysis Calculated as C ₂₅ H ₂₉ ClN ₂ O ₂ · HCl · 0.5H ₂ O: C, 63.83; H, 6.64; N, 5.95.
Experimental value: C, 63.68; H, 6.57; N, 5.80.

参考例３２で得た2-(3-フルオロフェニル)エチル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸 tert-ブチル(613mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(493mg) を融点182-184℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.00-7.20 (3H, m), 7.30-7.45 (1H, m), 7.73 (2H, s), 9.00-9.20 (2H, br). 8- (6-[[2- (3-Fluorophenyl) ethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (3-Fluorophenyl) ethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 32 The title compound (493 mg) was obtained as colorless crystals having a melting point of 182-184 ° C. by the same procedure as in Example 1 using -8-yl) hexyl] carbamate tert-butyl (613 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.25-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.85-3.25 (12H, m) , 3.99 (2H, t, J = 8.4Hz), 7.00-7.20 (3H, m), 7.30-7.45 (1H, m), 7.73 (2H, s), 9.00-9.20 (2H, br).

参考例３３で得た2-(2-メトキシフェニル)-1-メチルエチル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸 tert-ブチル(467mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(348mg) を淡黄色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ1.10 (3H, d, J = 6.3Hz), 1.25-1.50 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.60-2.80 (1H, m), 2.80-3.40 (10H, m), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.91 (1H, t, J = 7.2Hz), 7.00 (1H, d, J = 8.4Hz), 7.18 (1H, d, J = 7.2Hz), 7.26 (1H, t, J = 8.4Hz), 7.74 (2H, s), 9.00-9.20 (2H, br).
元素分析 C₂₇H₃₄N₂O₃・HCl・0.5H₂Oとして
計算値：C, 67.55; H, 7.56; N, 5.84.
実験値：C, 67.40; H, 7.55; N, 5.63. 8- (6-[[2- (2-methoxyphenyl) -1-methylethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- 4-one hydrochloride

2- (2-methoxyphenyl) -1-methylethyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1] obtained in Reference Example 33 -ij] Quinolin-8-yl) hexyl] carbamate tert-butyl (467 mg) was used for the same operation as in Example 1 to obtain the title compound (348 mg) as a pale yellow amorphous powder. .
¹ H NMR (300MHz, DMSO-d ₆ ) δ1.10 (3H, d, J = 6.3Hz), 1.25-1.50 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.60-2.80 (1H, m), 2.80-3.40 (10H, m), 3.80 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.91 (1H, t, J = 7.2Hz), 7.00 (1H, d, J = 8.4Hz), 7.18 (1H, d, J = 7.2Hz), 7.26 (1H, t, J = 8.4Hz), 7.74 (2H, s), 9.00-9.20 (2H, br).
Elemental analysis Calculated as C ₂₇ H ₃₄ N ₂ O ₃ · HCl · 0.5H ₂ O: C, 67.55; H, 7.56; N, 5.84.
Experimental value: C, 67.40; H, 7.55; N, 5.63.

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(650mg) およびN-メチル-N-(2-フェニルエチル)アミン(0.297ml) を用いて、実施例９と同様の操作を行うことにより、表題化合物(326mg) を融点83-85℃の無色結晶として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.35-1.50 (2H, m), 1.56 (2H, tt, J = 7.5, 7.5Hz), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.32 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.85 (2H, m), 2.91 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.15-7.35 (5H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₆H₃₂N₂O₂・HCl・0.5H₂Oとして
計算値：C, 69.39; H, 7.62; N, 6.23.
実験値：C, 69.08; H, 7.41; N, 6.09. 8- [6- [Methyl (2-phenylethyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (650 mg) and N-methyl obtained in Reference Example 2 The title compound (326 mg) was obtained as colorless crystals with a melting point of 83-85 ° C. by conducting the same operation as in Example 9 using -N- (2-phenylethyl) amine (0.297 ml).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.35-1.50 (2H, m), 1.56 (2H, tt, J = 7.5, 7.5 Hz), 1.75 (2H, tt, J = 7.5, 7.5 Hz), 2.32 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.85 (2H, m), 2.91 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.15-7.35 (5H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis Calculated as C ₂₆ H ₃₂ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 69.39; H, 7.62; N, 6.23.
Experimental value: C, 69.08; H, 7.41; N, 6.09.

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(282mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(100mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.35-1.45 (2H, m), 1.50-1.60 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.32 (3H, s), 2.43 (2H, t, J = 7.5Hz), 2.50-2.60 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.85 (2H, m), 2.91 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.82 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.80-6.85 (2H, m), 7.10-7.20 (2H, m), 7.67 (1H, s), 7.72 (1H, s). 8- [6-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and N- [ The title compound (100 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-methoxyphenyl) ethyl] -N-methylamine (282 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.35-1.45 (2H, m), 1.50-1.60 (2H, m), 1.75 (2H, tt, J = 7.5, 7.5 Hz), 2.32 (3H, s ), 2.43 (2H, t, J = 7.5Hz), 2.50-2.60 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.75-2.85 (2H, m), 2.91 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.82 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.80 -6.85 (2H, m), 7.10-7.20 (2H, m), 7.67 (1H, s), 7.72 (1H, s).

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(3-メトキシフェニル)エチル]-N-メチルアミン(282mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(528mg) を融点116-118℃の無色結晶として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.30-1.45 (2H, m), 1.50-1.60 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.30 (3H, s), 2.42 (2H, t, J = 7.5Hz), 2.55-2.80 (6H, m), 2.91 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.21 (2H, t, J = 8.4Hz), 3.78 (3H, s), 4.11 (2H, t, J = 8.4Hz), 6.70-6.85 (3H, m), 7.18 (1H, dt, J = 7.5, 0.9Hz), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₇H₃₄N₂O₃・HCl・H₂Oとして
計算値：C, 66.31; H, 7.63; N, 5.73.
実験値：C, 66.27; H, 7.49; N, 5.55. 8- [6-[[2- (3-Methoxyphenyl) ethyl] (methyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and N- [ 2- (3-Methoxyphenyl) ethyl] -N-methylamine (282 mg) was used for the same operation as in Example 9 to obtain the title compound (528 mg) as colorless crystals having a melting point of 116-118 ° C. It was.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.30-1.45 (2H, m), 1.50-1.60 (2H, m), 1.74 (2H, tt, J = 7.5, 7.5Hz), 2.30 (3H, s ), 2.42 (2H, t, J = 7.5Hz), 2.55-2.80 (6H, m), 2.91 (2H, t, J = 7.2Hz), 3.01 (2H, t, J = 7.8Hz), 3.21 (2H , t, J = 8.4Hz), 3.78 (3H, s), 4.11 (2H, t, J = 8.4Hz), 6.70-6.85 (3H, m), 7.18 (1H, dt, J = 7.5, 0.9Hz) , 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis _{C 27 H 34 N 2 O 3} · HCl · H 2 O Calculated: C, 66.31; H, 7.63 ; N, 5.73.
Experimental value: C, 66.27; H, 7.49; N, 5.55.

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(288mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(330mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.35-1.65 (4H, m), 1.75 (2H, quintet, J = 7.4Hz), 2.33 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.85-2.95 (4H, m), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.05-7.40 (4H, m), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₆H₃₁ClN₂O₂・HCl・0.5H₂Oとして
計算値：C, 64.46; H, 6.87; N, 5.78.
実験値：C, 64.75; H, 6.70; N, 5.65. 8- [6-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and N- [ The title compound (330 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-chlorophenyl) ethyl] -N-methylamine (288 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.35-1.65 (4H, m), 1.75 (2H, quintet, J = 7.4 Hz), 2.33 (3H, s), 2.44 (2H, t, J = 7.5 Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.5Hz), 2.85-2.95 (4H, m), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t , J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.05-7.40 (4H, m), 7.67 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₆ H ₃₁ ClN ₂ O ₂ · HCl · 0.5H ₂ O: C, 64.46; H, 6.87; N, 5.78.
Experimental value: C, 64.75; H, 6.70; N, 5.65.

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(3-クロロフェニル)エチル]-N-メチルアミン(288mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(235mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.35-1.60 (4H, m), 1.74 (2H, tt, J = 7.4, 7.4Hz), 2.29 (3H, s), 2.40 (2H, t, J = 7.5Hz), 2.50-2.80 (6H, m), 2.91 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.00-7.40 (4H, m), 7.67 (1H, s), 7.71 (1H, s). 8- [6-[[2- (3-Chlorophenyl) ethyl] (methyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and N- [ The title compound (235 mg) was obtained as a pale yellow amorphous powder by the same procedure as in Example 9 using 2- (3-chlorophenyl) ethyl] -N-methylamine (288 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.35-1.60 (4H, m), 1.74 (2H, tt, J = 7.4, 7.4 Hz), 2.29 (3H, s), 2.40 (2H, t, J = 7.5Hz), 2.50-2.80 (6H, m), 2.91 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.00-7.40 (4H, m), 7.67 (1H, s), 7.71 (1H, s).

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミン(241mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(120mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.35-1.65 (4H, m), 1.74 (2H, quintet, J = 7.4Hz), 2.29 (3H, s), 2.41 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.91 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m), 7.20-7.30 (1H, m), 7.67 (1H, s), 7.72 (1H, s). 8- [6-[[2- (3-Fluorophenyl) ethyl] (methyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) obtained in Reference Example 2 and N- [ The title compound (120 mg) was obtained as a pale yellow amorphous powder by the same procedure as in Example 9 using 2- (3-fluorophenyl) ethyl] -N-methylamine (241 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.35-1.65 (4H, m), 1.74 (2H, quintet, J = 7.4 Hz), 2.29 (3H, s), 2.41 (2H, t, J = 7.5 Hz), 2.55-2.65 (2H, m), 2.65-2.80 (4H, m), 2.91 (2H, t, J = 7.5Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t , J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m), 7.20-7.30 (1H, m), 7.67 (1H, s), 7.72 (1H, s) .

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-エチル-N-(2-フェニルエチル)アミン(234mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(140mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.05 (3H, t, J = 7.2Hz), 1.30-1.65 (4H, m), 1.75 (2H, tt, J = 7.5, 7.5Hz), 2.51 (2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7.2Hz), 2.65-2.80 (6H, m), 2.91 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.23 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.15-7.30 (5H, m), 7.67 (1H, s), 7.72 (1H, s). 8- [6- [Ethyl (2-phenylethyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and N-ethyl obtained in Reference Example 2 Using the same procedure as in Example 9 using -N- (2-phenylethyl) amine (234 mg), the title compound (140 mg) was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.05 (3H, t, J = 7.2 Hz), 1.30-1.65 (4H, m), 1.75 (2H, tt, J = 7.5, 7.5 Hz), 2.51 ( 2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7.2Hz), 2.65-2.80 (6H, m), 2.91 (2H, t, J = 7.2Hz), 3.02 (2H, t, J = 7.8Hz), 3.23 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.15-7.30 (5H, m), 7.67 (1H, s), 7.72 (1H, s ).

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-エチル-N-[2-(2-メトキシフェニル)エチル]アミン(281mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(190mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.07 (3H, t, J = 7.2Hz), 1.30-1.65 (4H, m), 1.76 (2H, tt, J = 7.4, 7.4Hz), 2.40-2.80 (10H, m), 2.91 (2H, t, J = 7.4Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.81 (3H,
s), 4.13 (2H, t, J = 8.4Hz), 6.80-6.95 (2H, m), 7.10-7.20 (2H, m), 7.67
(1H, s), 7.72 (1H, s). 8- (6- [Ethyl [2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and N-ethyl obtained in Reference Example 2 Using the same procedure as in Example 9 using -N- [2- (2-methoxyphenyl) ethyl] amine (281 mg), the title compound (190 mg) was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.07 (3H, t, J = 7.2 Hz), 1.30-1.65 (4H, m), 1.76 (2H, tt, J = 7.4, 7.4 Hz), 2.40- 2.80 (10H, m), 2.91 (2H, t, J = 7.4Hz), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 3.81 (3H,
s), 4.13 (2H, t, J = 8.4Hz), 6.80-6.95 (2H, m), 7.10-7.20 (2H, m), 7.67
(1H, s), 7.72 (1H, s).

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) およびN-イソプロピル-N-[2-(2-メトキシフェニル)エチル]アミン(425mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(400mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.00 (6H, d, J = 6.6Hz), 1.30-1.60 (4H, m), 1.75 (2H, tt, J = 7.4, 7.4Hz), 2.47 (2H, t, J = 7.5Hz), 2.55-2.75 (6H, m), 2.85-3.05 (5H, m), 3.21 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.90 (2H, m), 7.10-7.20 (2H, m), 7.67 (1H, s), 7.72 (1H, s). 8- (6- [Isopropyl [2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) and N-isopropyl obtained in Reference Example 2 The same operation as in Example 9 was performed using -N- [2- (2-methoxyphenyl) ethyl] amine (425 mg) to give the title compound (400 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.00 (6H, d, J = 6.6Hz), 1.30-1.60 (4H, m), 1.75 (2H, tt, J = 7.4, 7.4Hz), 2.47 ( 2H, t, J = 7.5Hz), 2.55-2.75 (6H, m), 2.85-3.05 (5H, m), 3.21 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.12 (2H , t, J = 8.4Hz), 6.80-6.90 (2H, m), 7.10-7.20 (2H, m), 7.67 (1H, s), 7.72 (1H, s).

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) およびN-[2-(2-クロロフェニル)エチル]-N-イソプロピルアミン(434mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(350mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.00 (6H, d, J = 6.6Hz), 1.30-1.55 (4H, m), 1.73 (2H, tt, J = 7.4, 7.4Hz), 2.46 (2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.05 (7H, m), 3.21 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.05-7.35 (4H, m), 7.67 (1H, s), 7.72 (1H, s). 8- [6-[[2- (2-Chlorophenyl) ethyl] (isopropyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) obtained in Reference Example 2 and N- [ The same operation as in Example 9 was carried out using 2- (2-chlorophenyl) ethyl] -N-isopropylamine (434 mg) to give the title compound (350 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.00 (6H, d, J = 6.6Hz), 1.30-1.55 (4H, m), 1.73 (2H, tt, J = 7.4, 7.4Hz), 2.46 ( 2H, t, J = 7.5Hz), 2.55-2.65 (2H, m), 2.71 (2H, t, J = 7.8Hz), 2.75-3.05 (7H, m), 3.21 (2H, t, J = 8.4Hz ), 4.12 (2H, t, J = 8.4Hz), 7.05-7.35 (4H, m), 7.67 (1H, s), 7.72 (1H, s).

参考例３４で得た5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル(3-フェニルプロピル)カルバミン酸 tert-ブチル(660mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(443mg) を融点116-118℃の無色結晶として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.50-1.80 (4H, m), 1.94 (2H, tt, J = 7.5, 7.5Hz), 2.50-2.70 (4H, m), 2.75-3.05 (8H, m), 3.17 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.15-7.35 (5H, m), 7.73 (2H, s), 8.80-9.10 (2H, br).
元素分析 C₂₅H₃₀N₂O₂・HCl・H₂Oとして
計算値：C, 67.48; H, 7.47; N, 6.30
実験値：C, 67.45; H, 7.71; N, 6.26. 8- [5-[(3-Phenylpropyl) amino] pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

5-Oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl (3-phenylpropiyl) obtained in Reference Example 34 The title compound (443 mg) was obtained as colorless crystals with a melting point of 116-118 ° C. by the same procedure as in Example 1 using tert-butyl carbamate (660 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.50-1.80 (4H, m), 1.94 (2H, tt, J = 7.5, 7.5Hz), 2.50-2.70 (4H, m), 2.75-3.05 (8H, m), 3.17 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.15-7.35 (5H, m), 7.73 (2H, s), 8.80-9.10 (2H, br ).
Elemental analysis Calculated as C ₂₅ H ₃₀ N ₂ O ₂ · HCl · H ₂ O: C, 67.48; H, 7.47; N, 6.30
Experimental values: C, 67.45; H, 7.71; N, 6.26.

参考例３５で得た6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル(3-フェニルプロピル)カルバミン酸 tert-ブチル(906mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(350mg) を融点132-134℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.50-1.75 (4H, m), 1.94 (2H, tt, J = 7.5, 7.5Hz), 2.59 (2H, t, J = 7.8Hz), 2.65 (2H, t, J = 7.8Hz), 2.75-3.00 (8H, m), 3.17 (2H, t, J = 8.4Hz), 3.98 (2H, t, J = 8.4Hz), 7.15-7.35 (5H, m), 7.72 (2H, s), 8.80-9.10 (2H, br). 8- [6-[(3-Phenylpropyl) amino] hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

6-Oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl (3-phenylpropylene) obtained in Reference Example 35 The title compound (350 mg) was obtained as colorless crystals having a melting point of 132-134 ° C. by the same procedure as in Example 1 using tert-butyl carbamate (906 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.50-1.75 (4H, m), 1.94 (2H, tt, J = 7.5, 7.5Hz), 2.59 (2H, t, J = 7.8Hz), 2.65 (2H, t, J = 7.8Hz), 2.75-3.00 (8H, m), 3.17 (2H, t, J = 8.4Hz), 3.98 (2H, t, J = 8.4Hz) , 7.15-7.35 (5H, m), 7.72 (2H, s), 8.80-9.10 (2H, br).

参考例３６で得た2-(2-メトキシフェニル)エチル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物(535mg) を融点169-170℃の淡黄色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.61-1.73 (4H, m), 1.88-1.97 (2H, m), 2.76 (2H, t, J = 6Hz), 2.93-3.00 (8H, m), 3.57 (2H, s), 3.60 (2H, t, J = 6Hz), 3.79 (3H, s), 6.89 (1H, t, J = 7.5Hz) 6.98 (1H, d, J = 7.5Hz), 7.17 (1H, d, J = 7.4Hz), 7.24 (1H, t, J = 7.4Hz), 7.71 (1H, s), 7.75 (1H, s), 9.12 (2H, br s).
IR (KBr) νcm^-1: 3418, 2951, 2771, 1708, 1670, 1604, 1498, 1343, 1251, 1150.
元素分析 C₂₅H₃₀N₂O₃・HClとして
計算値：C, 67.78; H, 7.05; N, 6.32.
実験値：C, 67.45; H, 7.01; N, 6.27. 8- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

2- (2-Methoxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 36 The title compound (535 mg) was obtained as pale yellow crystals having a melting point of 169-170 ° C. by the same procedure as in Example 1 using -8-yl) pentyl] carbamate tert-butyl.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.61-1.73 (4H, m), 1.88-1.97 (2H, m), 2.76 (2H, t, J = 6Hz), 2.93-3.00 (8H, m), 3.57 (2H, s), 3.60 (2H, t, J = 6Hz), 3.79 (3H, s), 6.89 (1H, t, J = 7.5Hz) 6.98 (1H, d, J = 7.5Hz), 7.17 ( 1H, d, J = 7.4Hz), 7.24 (1H, t, J = 7.4Hz), 7.71 (1H, s), 7.75 (1H, s), 9.12 (2H, br s).
IR (KBr) νcm ^-1 : 3418, 2951, 2771, 1708, 1670, 1604, 1498, 1343, 1251, 1150.
Elemental analysis Calculated as C ₂₅ H ₃₀ N ₂ O ₃ .HCl: C, 67.78; H, 7.05; N, 6.32.
Experimental value: C, 67.45; H, 7.01; N, 6.27.

参考例３７で得た2-(2-クロロフェニル)エチル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物(585mg) を融点179-180℃の淡黄色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.66-1.72 (4H, m), 1.88-1.94 (2H, m), 2.76 (2H, t, J = 6Hz), 2.96-3.01 (4H, m), 3.11-3.15 (4H, m), 3.57 (2H, s), 3.60 (2H, t, J = 6Hz), 7.27-7.34 (2H, m), 7.38-7.41 (1H, m), 7.44-7.46 (1H, m), 7.71 (1H, s), 7.75 (1H, s), 9.25 (2H, br s).
IR (KBr)νcm^-1: 3424, 2952, 2772, 1709, 1666, 1602, 1499, 1341, 1149.
元素分析 C₂₄H₂₇ClN₂O₂・HClとして
計算値：C, 64.43; H, 6.31; N, 6.26.
実験値：C, 64.08; H, 6.36; N, 5.96. 8- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

2- (2-Chlorophenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- obtained in Reference Example 37 The same operation as in Example 1 was carried out using tert-butyl 8-yl) pentyl] carbamate to obtain the title compound (585 mg) as pale yellow crystals having a melting point of 179-180 ° C.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.66-1.72 (4H, m), 1.88-1.94 (2H, m), 2.76 (2H, t, J = 6Hz), 2.96-3.01 (4H, m), 3.11-3.15 (4H, m), 3.57 (2H, s), 3.60 (2H, t, J = 6Hz), 7.27-7.34 (2H, m), 7.38-7.41 (1H, m), 7.44-7.46 (1H m), 7.71 (1H, s), 7.75 (1H, s), 9.25 (2H, br s).
IR (KBr) νcm ^-1 : 3424, 2952, 2772, 1709, 1666, 1602, 1499, 1341, 1149.
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ .HCl: C, 64.43; H, 6.31; N, 6.26.
Experimental value: C, 64.08; H, 6.36; N, 5.96.

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(297mg) を無色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.53-1.61 (2H, m), 1.71-1.78 (2H, m), 2.00-2.06 (2H, m), 2.30 (3H, s), 2.45 (2H, t, J = 7.4Hz), 2.58-2.62 (2H, m), 2.75-2.83 (4H, m), 2.93 (2H, t, J = 7.4Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.16-7.29 (5H, m), 7.73 (2H, s).
IR (フリー塩基; KBr)νcm^-1: 1718, 1673, 1604, 1496, 1343, 1151. 8- [5- [Methyl (2-phenylethyl) amino] pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N-methyl-N- () obtained in Reference Example 3 The title compound (297 mg) was obtained as a colorless amorphous powder by the same operation as in Example 9 using 2-phenylethyl) amine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.53-1.61 (2H, m), 1.71-1.78 (2H, m), 2.00-2.06 (2H, m), 2.30 (3H, s), 2.45 (2H , t, J = 7.4Hz), 2.58-2.62 (2H, m), 2.75-2.83 (4H, m), 2.93 (2H, t, J = 7.4Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.16-7.29 (5H, m), 7.73 (2H, s).
IR (free base; KBr) νcm ^-1 : 1718, 1673, 1604, 1496, 1343, 1151.

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(292mg) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(363mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(130mg) をW黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.55-1.63 (2H, m), 1.72-1.79 (2H, m), 2.00-2.06 (2H, m), 2.32 (3H, s), 2.47 (2H, t, J = 7.5Hz), 2.56-2.60 (2H, m), 2.77-2.83 (4H, m), 2.94 (2H, t, J = 7.5Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 7.74 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1716, 1672, 1603, 1495, 1343, 1243, 1152. 8- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (292 mg) and N- [2 obtained in Reference Example 3 The title compound (130 mg) was obtained as a W yellow amorphous powder by conducting the same operation as in Example 9 using-(2-methoxyphenyl) ethyl] -N-methylamine (363 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.55-1.63 (2H, m), 1.72-1.79 (2H, m), 2.00-2.06 (2H, m), 2.32 (3H, s), 2.47 (2H , t, J = 7.5Hz), 2.56-2.60 (2H, m), 2.77-2.83 (4H, m), 2.94 (2H, t, J = 7.5Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 7.74 (2H, s).
IR (free base; KBr) νcm ^-1 : 1716, 1672, 1603, 1495, 1343, 1243, 1152.

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(85mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.56-1.64 (2H, m), 1.71-1.79 (2H, m), 2.00-2.07 (2H, m), 2.36 (3H, s), 2.50 (2H, t, J = 7.5Hz), 2.61-2.67 (2H, m), 2.82 (2H, t, J = 6Hz), 2.90-2.95 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.11-7.25 (3H, m), 7.32 (1H, dd, J = 5.5, 2Hz) 7.74 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1716, 1672, 1604, 1496, 1343, 1151. 8- [5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one Hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N- [2- (2) obtained in Reference Example 3 -Chlorophenyl) ethyl] -N-methylamine was used for the same operation as in Example 9 to obtain the title compound (85 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.56-1.64 (2H, m), 1.71-1.79 (2H, m), 2.00-2.07 (2H, m), 2.36 (3H, s), 2.50 (2H , t, J = 7.5Hz), 2.61-2.67 (2H, m), 2.82 (2H, t, J = 6Hz), 2.90-2.95 (4H, m), 3.55 (2H, s), 3.74 (2H, t , J = 6Hz), 7.11-7.25 (3H, m), 7.32 (1H, dd, J = 5.5, 2Hz) 7.74 (2H, s).
IR (free base; KBr) νcm ^-1 : 1716, 1672, 1604, 1496, 1343, 1151.

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(68mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.52-1.60 (2H, m), 1.72-1.78 (2H, m), 2.00-2.08 (2H, m), 2.29 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.74-2.78 (2H, m), 2.82 (2H, t, J = 6Hz), 2.93 (2H, t, J = 7Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 6.85-6.93 (2H, m), 6.96 (1H, d, J = 7.5Hz), 7.20-7.25 (1H, m), 7.73 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1717, 1673, 1604, 1496, 1343, 1151. 8- [5-[[2- (3-Fluorophenyl) ethyl] (methyl) amino] pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H)- On hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N- [2- (3 The title compound (68 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -fluorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.52-1.60 (2H, m), 1.72-1.78 (2H, m), 2.00-2.08 (2H, m), 2.29 (3H, s), 2.44 (2H , t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.74-2.78 (2H, m), 2.82 (2H, t, J = 6Hz), 2.93 (2H, t, J = 7Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 6.85-6.93 (2H, m), 6.96 (1H, d, J = 7.5Hz), 7.20-7.25 (1H, m), 7.73 (2H , s).
IR (free base; KBr) νcm ^-1 : 1717, 1673, 1604, 1496, 1343, 1151.

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-エチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(45mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.05 (3H, t, J = 7Hz), 1.54-1.59 (2H, m), 1.70-1.78 (2H, m), 2.00-2.06 (2H, m), 2.54 (2H, t, J = 7Hz), 2.61 (2H, q, J = 7Hz), 2.68-2.75 (4H, m), 2.82 (2H, t, J = 6Hz), 2.92 (2H, t, J = 6Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.16-7.19 (3H, m) 7.25-7.30 (2H, m), 7.73 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1718, 1671, 1603, 1496, 1342, 1150. 8- [5- [Ethyl (2-phenylethyl) amino] pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N-ethyl-N- (obtained in Reference Example 3 The title compound (45 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2-phenylethyl) amine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.05 (3H, t, J = 7 Hz), 1.54-1.59 (2H, m), 1.70-1.78 (2H, m), 2.00-2.06 (2H, m) , 2.54 (2H, t, J = 7Hz), 2.61 (2H, q, J = 7Hz), 2.68-2.75 (4H, m), 2.82 (2H, t, J = 6Hz), 2.92 (2H, t, J = 6Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.16-7.19 (3H, m) 7.25-7.30 (2H, m), 7.73 (2H, s).
IR (free base; KBr) νcm ^-1 : 1718, 1671, 1603, 1496, 1342, 1150.

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-エチル-N-[2-(2-メトキシフェニル)エチル]アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(44mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.07 (3H, t, J = 7Hz), 1.57-1.62 (2H, m), 1.71-1.79 (2H, m), 1.99-2.06 (2H, m), 2.57 (2H, t, J = 7Hz), 2.62 (2H, q, J = 7Hz), 2.66-2.70 (2H, m), 2.73-2.78 (2H, m), 2.82 (2H, t, J = 6Hz), 2.93 (2H, t, J = 6Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (3H, m), 7.11-7.19 (2H, m), 7.74 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1717, 1672, 1602, 1494, 1342, 1243, 1150. 8- (5- [Ethyl [2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloric acid salt

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N-ethyl-N- [obtained in Reference Example 3 The title compound (44 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-methoxyphenyl) ethyl] amine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.07 (3H, t, J = 7 Hz), 1.57-1.62 (2H, m), 1.71-1.79 (2H, m), 1.99-2.06 (2H, m) , 2.57 (2H, t, J = 7Hz), 2.62 (2H, q, J = 7Hz), 2.66-2.70 (2H, m), 2.73-2.78 (2H, m), 2.82 (2H, t, J = 6Hz ), 2.93 (2H, t, J = 6Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (3H, m), 7.11-7.19 (2H, m), 7.74 (2H, s).
IR (free base; KBr) νcm ^-1 : 1717, 1672, 1602, 1494, 1342, 1243, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(350mg) および２-フェニルエチルアミン(364mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(73mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.35-1.42 (2H, m), 1.49-1.56 (2H, m), 1.60 (1H, br s), 1.69-1.77 (2H, m), 2.00-2.06 (2H, m), 2.63 (2H, t, J = 7.4Hz), 2.75-2.97 (8H, m), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.18-7.31 (5H, m), 7.72 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1716, 1672, 1604, 1496, 1343, 1150. 8- [6-[(2-Phenylethyl) amino] hexanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (350 mg) and 2-phenylethylamine obtained in Reference Example 4 (364 mg) was used in the same manner as in Example 9 to give the titled compound (73 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.35-1.42 (2H, m), 1.49-1.56 (2H, m), 1.60 (1H, br s), 1.69-1.77 (2H, m), 2.00- 2.06 (2H, m), 2.63 (2H, t, J = 7.4Hz), 2.75-2.97 (8H, m), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.18-7.31 ( 5H, m), 7.72 (2H, s).
IR (free base; KBr) νcm ^-1 : 1716, 1672, 1604, 1496, 1343, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよび2-(2−メトキシフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(190mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.36-1.43 (2H, m), 1.49-1.57 (3H, m), 1.70-1.77 (2H, m), 2.00-2.06 (2H, m), 2.64 (2H, t, J = 7.4Hz), 2.80-2.83 (6H, m), 2.90 (2H, t, J = 7.4Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 3.81 (3H, s), 6.86 (1H, t, J = 8.3Hz), 6.89 (1H, d, J = 7.3Hz), 7.13-7.21 (2H, m), 7.72 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1715, 1672, 1603, 1495, 1343, 1242, 1150. 8- (6-[[2- (2-Methoxyphenyl) ethyl] amino] hexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and 2- (2-methoxyphenyl) obtained in Reference Example 4 ) The title compound (190 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using ethylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.36-1.43 (2H, m), 1.49-1.57 (3H, m), 1.70-1.77 (2H, m), 2.00-2.06 (2H, m), 2.64 (2H, t, J = 7.4Hz), 2.80-2.83 (6H, m), 2.90 (2H, t, J = 7.4Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 3.81 (3H, s), 6.86 (1H, t, J = 8.3Hz), 6.89 (1H, d, J = 7.3Hz), 7.13-7.21 (2H, m), 7.72 (2H, s).
IR (free base; KBr) νcm ^-1 : 1715, 1672, 1603, 1495, 1343, 1242, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよび2-(2−クロロフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(30mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.37-1.45 (2H, m), 1.51-1.58 (2H, m), 1.56 (1H, br s), 1.71-1.78 (2H, m), 2.00-2.07 (2H, m), 2.66 (2H, t, J = 7.5Hz), 2.82 (2H, t, J = 6Hz), 2.85-2.98 (6H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.13-7.25 (3H, m), 7.34 (1H, dd, J = 7, 2Hz), 7.73 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1715, 1671, 1604, 1496, 1343, 1150. 8- (6-[[2- (2-Chlorophenyl) ethyl] amino] hexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and 2- (2-chlorophenyl) obtained in Reference Example 4 The title compound (30 mg) was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using ethylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.37-1.45 (2H, m), 1.51-1.58 (2H, m), 1.56 (1H, br s), 1.71-1.78 (2H, m), 2.00- 2.07 (2H, m), 2.66 (2H, t, J = 7.5Hz), 2.82 (2H, t, J = 6Hz), 2.85-2.98 (6H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.13-7.25 (3H, m), 7.34 (1H, dd, J = 7, 2Hz), 7.73 (2H, s).
IR (free base; KBr) νcm ^-1 : 1715, 1671, 1604, 1496, 1343, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(292mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.36-1.42 (2H, m), 1.50-1.58 (2H, m), 1.71-1.78 (2H, m), 2.00-2.06 (2H, m), 2.30 (3H, s), 2.41 (2H, t, J = 7Hz), 2.58-2.62 (2H, m), 2.75-2.83 (4H, m), 2.91 (2H, t, J = 7Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 7.16-7.29 (5H, m), 7.73 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1718, 1673, 1604, 1496, 1343, 1151. 8- [6-[(2-Phenylethyl) amino] hexanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N-methyl-N- () obtained in Reference Example 4 The title compound (292 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using 2-phenylethyl) amine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.36-1.42 (2H, m), 1.50-1.58 (2H, m), 1.71-1.78 (2H, m), 2.00-2.06 (2H, m), 2.30 (3H, s), 2.41 (2H, t, J = 7Hz), 2.58-2.62 (2H, m), 2.75-2.83 (4H, m), 2.91 (2H, t, J = 7Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 7.16-7.29 (5H, m), 7.73 (2H, s).
IR (free base; KBr) νcm ^-1 : 1718, 1673, 1604, 1496, 1343, 1151.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(250mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.37-1.43 (2H, m), 1.51-1.59 (2H, m), 1.71-1.79 (2H, m), 2.00-2.06 (2H, m), 2.31 (3H, s), 2.42 (2H, t, J = 7.5Hz), 2.55-2.59 (2H, m), 2.76-2.83 (4H, m), 2.92 (2H, t, J = 7.5Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 7.74 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1715, 1672, 1603, 1495, 1343, 1242, 1150. 8- (6-[[2- (2-Methoxyphenyl) ethyl] amino] hexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N- [2- (2) obtained in Reference Example 4 The title compound (250 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.37-1.43 (2H, m), 1.51-1.59 (2H, m), 1.71-1.79 (2H, m), 2.00-2.06 (2H, m), 2.31 (3H, s), 2.42 (2H, t, J = 7.5Hz), 2.55-2.59 (2H, m), 2.76-2.83 (4H, m), 2.92 (2H, t, J = 7.5Hz), 3.54 ( 2H, s), 3.73 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 7.74 (2H, s).
IR (free base; KBr) νcm ^-1 : 1715, 1672, 1603, 1495, 1343, 1242, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(256mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.37-1.43 (2H, m), 1.51-1.58 (2H, m), 1.71-1.79 (2H, m), 2.00-2.06 (2H, m), 2.33 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.82 (2H, t, J = 6Hz), 2.88-2.94 (4H, m), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 7.11-7.24 (3H, m), 7.32 (1H, dd, J = 5.5, 2Hz), 7.73 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1718, 1673, 1604, 1496, 1343, 1151. 8- (6-[[2- (2-Chlorophenyl) ethyl] amino] hexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N- [2- (2) obtained in Reference Example 4 -Chlorophenyl) ethyl] -N-methylamine was used for the same operation as in Example 9 to obtain the title compound (256 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.37-1.43 (2H, m), 1.51-1.58 (2H, m), 1.71-1.79 (2H, m), 2.00-2.06 (2H, m), 2.33 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.82 (2H, t, J = 6Hz), 2.88-2.94 (4H, m), 3.54 (2H , s), 3.74 (2H, t, J = 6Hz), 7.11-7.24 (3H, m), 7.32 (1H, dd, J = 5.5, 2Hz), 7.73 (2H, s).
IR (free base; KBr) νcm ^-1 : 1718, 1673, 1604, 1496, 1343, 1151.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(190mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.36-1.42 (2H, m), 1.49-1.57 (2H, m), 1.71-1.78 (2H, m), 2.00-2.07 (2H, m), 2.29 (3H, s), 2.40 (2H, t, J = 7.5Hz), 2.57-2.61 (2H, m), 2.74-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 3.54 (2H, s), 3.74 (2H, t, J = 6Hz), 6.85-6.91 (2H, m), 6.97 (1H, d, J = 7.5Hz), 7.20-7.25 (1H, m), 7.74 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1717, 1672, 1604, 1496, 1343, 1150. 8- (6-[[2- (3-Fluorophenyl) ethyl] amino] hexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N- [2- (3) obtained in Reference Example 4 The title compound (190 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -fluorophenyl) ethyl] -N-methylamine.
¹ H NMR (free _{base; 400MHz, CDCl 3) δ 1.36-1.42} (2H, m), 1.49-1.57 (2H, m), 1.71-1.78 (2H, m), 2.00-2.07 (2H, m), 2.29 (3H, s), 2.40 (2H, t, J = 7.5Hz), 2.57-2.61 (2H, m), 2.74-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 3.54 (2H , s), 3.74 (2H, t, J = 6Hz), 6.85-6.91 (2H, m), 6.97 (1H, d, J = 7.5Hz), 7.20-7.25 (1H, m), 7.74 (2H, s ).
IR (free base; KBr) νcm ^-1 : 1717, 1672, 1604, 1496, 1343, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-エチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(137mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.05 (3H, t, J = 7Hz), 1.36-1.42 (2H, m), 1.49-1.56 (2H, m), 1.71-1.79 (2H, m), 2.00-2.06 (2H, m), 2.50 (2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7Hz), 2.67-2.76 (4H, m), 2.82 (2H, t, J = 6Hz), 2.91 (2H, t, J = 6Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 7.16-7.19 (3H, m), 7.25-7.29 (2H, m), 7.73 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1718, 1673, 1604, 1496, 1342, 1150. 8- [6- [Ethyl (2-phenylethyl) amino] hexanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N-ethyl-N- () obtained in Reference Example 4 The title compound (137 mg) was obtained as a pale yellow amorphous powder by the same operation as in Example 9 using 2-phenylethyl) amine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.05 (3H, t, J = 7 Hz), 1.36-1.42 (2H, m), 1.49-1.56 (2H, m), 1.71-1.79 (2H, m) , 2.00-2.06 (2H, m), 2.50 (2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7Hz), 2.67-2.76 (4H, m), 2.82 (2H, t, J = 6Hz), 2.91 (2H, t, J = 6Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 7.16-7.19 (3H, m), 7.25-7.29 (2H, m), 7.73 (2H, s).
IR (free base; KBr) νcm ^-1 : 1718, 1673, 1604, 1496, 1342, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オンおよびN-エチル-N-[2-(2-メトキシフェニル)エチル]アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(145mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.06 (3H, t, J = 7Hz), 1.37-1.43 (2H, m), 1.51-1.59 (2H, m), 1.72-1.80 (2H, m), 2.00-2.06 (2H, m), 2.52 (2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7Hz), 2.66-2.69 (2H, m), 2.72-2.77 (2H, m), 2.82 (2H, t, J = 6Hz), 2.92 (2H, t, J = 6Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (2H, m), 7.11-7.19 (2H, m), 7.73 (2H, s).
IR (フリー塩基; KBr) νcm^-1: 1718, 1673, 1603, 1495, 1342, 1242, 1150. 8- (6- [Ethyl [2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloric acid salt

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and N-ethyl-N- [obtained in Reference Example 4 The title compound (145 mg) was obtained as a pale yellow amorphous powder by the same operation as in Example 9 using 2- (2-methoxyphenyl) ethyl] amine.
¹ H NMR (free _{base; 400MHz, CDCl 3) δ 1.06} (3H, t, J = 7Hz), 1.37-1.43 (2H, m), 1.51-1.59 (2H, m), 1.72-1.80 (2H, m) , 2.00-2.06 (2H, m), 2.52 (2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7Hz), 2.66-2.69 (2H, m), 2.72-2.77 (2H, m) , 2.82 (2H, t, J = 6Hz), 2.92 (2H, t, J = 6Hz), 3.54 (2H, s), 3.73 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83- 6.89 (2H, m), 7.11-7.19 (2H, m), 7.73 (2H, s).
IR (free base; KBr) νcm ^-1 : 1718, 1673, 1603, 1495, 1342, 1242, 1150.

参考例４で得た8-(6-ブロモヘキサノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(350mg) およびN-イソプロピル-N-[2-(2-メトキシフェニル)エチル]アミン(425mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(45mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.00 (6H, d, J = 6.3Hz), 1.36-1.42 (2H, m), 1.48-1.55 (2H, m), 1.71-1.78 (2H, m), 1.99-2.05 (2H, m), 2.46 (2H, t, J = 7.3Hz), 2.56-2.60 (2H, m), 2.69-2.73 (2H, m), 2.81 (2H, t, J = 6Hz), 2.91 (2H, t, J = 7.3Hz), 2.99 (1H, q, J = 6.3Hz), 3.53 (2H, s), 3.72 (2H, t, J = 6Hz), 3.81 (3H, s), 6.82-6.88 (2H, m), 7.10-7.18 (2H, m), 7.73 (2H, s).
IR (フリー塩基; neat) νcm^-1: 1713, 1674, 1603, 1495, 1344, 1243, 1150. 8- (6- [Isopropyl [2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloric acid salt

8- (6-Bromohexanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (350 mg) and N-isopropyl- obtained in Reference Example 4 The same operation as in Example 9 was performed using N- [2- (2-methoxyphenyl) ethyl] amine (425 mg) to give the title compound (45 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.00 (6H, d, J = 6.3 Hz), 1.36-1.42 (2H, m), 1.48-1.55 (2H, m), 1.71-1.78 (2H, m ), 1.99-2.05 (2H, m), 2.46 (2H, t, J = 7.3Hz), 2.56-2.60 (2H, m), 2.69-2.73 (2H, m), 2.81 (2H, t, J = 6Hz ), 2.91 (2H, t, J = 7.3Hz), 2.99 (1H, q, J = 6.3Hz), 3.53 (2H, s), 3.72 (2H, t, J = 6Hz), 3.81 (3H, s) , 6.82-6.88 (2H, m), 7.10-7.18 (2H, m), 7.73 (2H, s).
IR (free base; neat) νcm ^-1 : 1713, 1674, 1603, 1495, 1344, 1243, 1150.

参考例３８で得た5-オキソ-5-(3-オキソ-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-9-イル)ペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(315mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(264mg) を黄色非晶状粉末として得た。
¹H NMR(400MHz, CD₃OD) δ 1.71-1.85 (4H, m), 1.98-2.02 (2H, m), 2.69 (2H, t, J = 7Hz), 2.90 (2H, t, J = 6Hz), 3.00 (2H, t, J = 7Hz), 3.04-3.08 (2H, m), 3.10-3.14 (4H, m), 3.28-3.32 (2H, m), 3.90 (2H, t, J = 6Hz), 4.88 (2H, s), 7.29-7.41 (5H, m), 7.74 (2H, d, J = 4Hz).
IR (neat) νcm^-1: 3427, 1670, 1604, 1484, 1366, 1298, 1165. 9- [5-[(2-Phenylethyl) amino] pentanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

5-oxo-5- (3-oxo-2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-9-yl) pentyl (2) obtained in Reference Example 38 The title compound (264 mg) was obtained as a yellow amorphous powder by the same procedure as in Example 1 using tert-butyl (phenylethyl) carbamate (315 mg).
¹ H NMR (400MHz, CD ₃ OD) δ 1.71-1.85 (4H, m), 1.98-2.02 (2H, m), 2.69 (2H, t, J = 7Hz), 2.90 (2H, t, J = 6Hz) , 3.00 (2H, t, J = 7Hz), 3.04-3.08 (2H, m), 3.10-3.14 (4H, m), 3.28-3.32 (2H, m), 3.90 (2H, t, J = 6Hz), 4.88 (2H, s), 7.29-7.41 (5H, m), 7.74 (2H, d, J = 4Hz).
IR (neat) νcm ^-1 : 3427, 1670, 1604, 1484, 1366, 1298, 1165.

参考例３９で得た2-(2-メトキシフェニル)エチル[5-オキソ-5-(3-オキソ-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-9-イル)ペンチル]カルバミン酸 tert-ブチル(410mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(315mg) を黄色非晶状粉末として得た。
¹H NMR(400MHz, CD₃OD) δ 1.71-1.78 (4H, m), 1.85-1.91 (2H, m), 2.57 (2H, t, J = 7Hz), 2.79 (2H, t, J = 7Hz), 2.88 (2H, t, J = 7Hz), 2.96-3.03 (6H, m), 3.17 (2H, t, J = 7Hz), 3.77 (2H, t, J = 7.5Hz), 3.81 (3H, s), 4.79 (2H, s), 6.87 (1H, t, J = 7Hz), 6.93 (1H, d, J = 8Hz), 7.17 (1H, d, J = 7Hz), 7.22 (1H, t, J = 7Hz), 7.64 (2H, d, J = 4Hz).
IR (neat) νcm^-1: 3431, 1671, 1603, 1496, 1439, 1366, 1247, 1165. 9- (5-[[2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5- On hydrochloride

2- (2-Methoxyphenyl) ethyl [5-oxo-5- (3-oxo-2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] obtained in Reference Example 39 The title compound (315 mg) was obtained as a yellow amorphous powder by conducting the same operation as in Example 1 using [quinoline-9-yl) pentyl] carbamate tert-butyl (410 mg).
¹ H NMR (400MHz, CD ₃ OD) δ 1.71-1.78 (4H, m), 1.85-1.91 (2H, m), 2.57 (2H, t, J = 7Hz), 2.79 (2H, t, J = 7Hz) , 2.88 (2H, t, J = 7Hz), 2.96-3.03 (6H, m), 3.17 (2H, t, J = 7Hz), 3.77 (2H, t, J = 7.5Hz), 3.81 (3H, s) , 4.79 (2H, s), 6.87 (1H, t, J = 7Hz), 6.93 (1H, d, J = 8Hz), 7.17 (1H, d, J = 7Hz), 7.22 (1H, t, J = 7Hz ), 7.64 (2H, d, J = 4Hz).
IR (neat) νcm ^-1 : 3431, 1671, 1603, 1496, 1439, 1366, 1247, 1165.

参考例４０で得た2-(2-クロロフェニル)エチル[5-オキソ-5-(3-オキソ-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-9-イル)ペンチル]カルバミン酸 tert-ブチル(380mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(235mg) を融点108-109℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.62-1.72 (4H, m), 1.81-1.87 (2H, m), 2.56 (2H, t, J = 6Hz), 2.79 (2H, t, J = 6Hz), 2.90 (2H, t, J = 7Hz), 2.92-3.02 (4H, m), 3.05-3.16 (4H, m), 3.75 (2H, t, J = 6Hz), 7.24-7.35 (2H, m), 7.39 (1H, dd, J = 7, 2Hz), 7.45 (1H, dd, J = 7, 2Hz), 7.66 (2H, s), 9.18 (2H, s).
IR (KBr) νcm^-1: 3429, 2948, 1671, 1603, 1363, 1338, 1165. 9- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one Hydrochloride

2- (2-Chlorophenyl) ethyl [5-oxo-5- (3-oxo-2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] obtained in Reference Example 40 The title compound (235 mg) was obtained as colorless crystals with a melting point of 108-109 ° C. by the same procedure as in Example 1 using tert-butyl (quinolin-9-yl) pentyl] carbamate (380 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.72 (4H, m), 1.81-1.87 (2H, m), 2.56 (2H, t, J = 6Hz), 2.79 (2H, t, J = 6Hz ), 2.90 (2H, t, J = 7Hz), 2.92-3.02 (4H, m), 3.05-3.16 (4H, m), 3.75 (2H, t, J = 6Hz), 7.24-7.35 (2H, m) , 7.39 (1H, dd, J = 7, 2Hz), 7.45 (1H, dd, J = 7, 2Hz), 7.66 (2H, s), 9.18 (2H, s).
IR (KBr) νcm ^-1 : 3429, 2948, 1671, 1603, 1363, 1338, 1165.

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(310mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.53-1.61 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.31 (3H, s), 2.45 (2H, t, J = 7.4Hz), 2.59-2.63 (2H, m), 2.66-2.69 (2H, m), 2.75-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 2.91-2.95 (4H, m), 3.89 (2H, t, J = 6Hz), 7.17-7.29 (5H, m), 7.61 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1676, 1604, 1590, 1484, 1361, 1339, 1161. 9- [5- [Methyl (2-phenylethyl) amino] pentanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N-methyl- obtained in Reference Example 5 The same operation as in Example 9 was performed using N- (2-phenylethyl) amine to give the title compound (310 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.53-1.61 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.31 (3H, s), 2.45 (2H , t, J = 7.4Hz), 2.59-2.63 (2H, m), 2.66-2.69 (2H, m), 2.75-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 2.91-2.95 (4H, m), 3.89 (2H, t, J = 6Hz), 7.17-7.29 (5H, m), 7.61 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1676, 1604, 1590, 1484, 1361, 1339, 1161.

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(165mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.55-1.62 (2H, m), 1.71-1.79 (2H, m), 1.93-1.99 (2H, m), 2.32 (3H, s), 2.46 (2H, t, J = 7.4Hz), 2.56-2.60 (2H, m), 2.68 (2H, t, J = 6Hz), 2.77-2.80 (2H, m), 2.84 (2H, t, J = 6Hz), 2.91-2.95 (4H, m), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1674, 1603, 1494, 1361, 1339, 1243, 1160. 9- [5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline -5-one hydrochloride

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N- [2 obtained in Reference Example 5 The title compound (165 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using-(2-methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.55-1.62 (2H, m), 1.71-1.79 (2H, m), 1.93-1.99 (2H, m), 2.32 (3H, s), 2.46 (2H , t, J = 7.4Hz), 2.56-2.60 (2H, m), 2.68 (2H, t, J = 6Hz), 2.77-2.80 (2H, m), 2.84 (2H, t, J = 6Hz), 2.91 -2.95 (4H, m), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1674, 1603, 1494, 1361, 1339, 1243, 1160.

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(188mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.54-1.62 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.32 (3H, s), 2.48 (2H, t, J = 7Hz), 2.59-2.63 (2H, m), 2.67 (2H, t, J = 6Hz), 2.84 (2H, t, J = 6Hz), 2.88-2.96 (6H, m), 3.89 (2H, t, J = 6Hz), 7.11-7.24 (3H, m), 7.32 (1H, d, d, J = 5, 2Hz), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1673, 1604, 1483, 1438, 1361, 1159. 9- [5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline- 5-one hydrochloride

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N- [2 obtained in Reference Example 5 The title compound (188 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using-(2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.62 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.32 (3H, s), 2.48 (2H , t, J = 7Hz), 2.59-2.63 (2H, m), 2.67 (2H, t, J = 6Hz), 2.84 (2H, t, J = 6Hz), 2.88-2.96 (6H, m), 3.89 ( 2H, t, J = 6Hz), 7.11-7.24 (3H, m), 7.32 (1H, d, d, J = 5, 2Hz), 7.62 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1673, 1604, 1483, 1438, 1361, 1159.

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-エチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(45mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.05 (3H, t, J = 7Hz), 1.52-1.60 (2H, m), 1.70-1.77 (2H, m), 1.95-1.99 (2H, m), 2.55 (2H, t, J = 7Hz), 2.61 (2H, q, J = 7Hz), 2.65-2.77 (6H, m), 2.84 (2H, t, J = 6Hz), 2.89-2.97 (4H, m), 3.89 (2H, t, J = 6Hz), 7.16-7.19 (3H, m), 7.25-7.30 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1675, 1604, 1484, 1361, 1299, 1160. 9- [5- [Ethyl (2-phenylethyl) amino] pentanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N-ethyl- obtained in Reference Example 5 The same operation as in Example 9 was performed using N- (2-phenylethyl) amine to give the title compound (45 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.05 (3H, t, J = 7 Hz), 1.52-1.60 (2H, m), 1.70-1.77 (2H, m), 1.95-1.99 (2H, m) , 2.55 (2H, t, J = 7Hz), 2.61 (2H, q, J = 7Hz), 2.65-2.77 (6H, m), 2.84 (2H, t, J = 6Hz), 2.89-2.97 (4H, m ), 3.89 (2H, t, J = 6Hz), 7.16-7.19 (3H, m), 7.25-7.30 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1675, 1604, 1484, 1361, 1299, 1160.

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-エチル-N-[2-(2-メトキシフェニル)エチル]アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(70mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.07 (3H, t, J = 7Hz), 1.55-1.62 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.56 (2H, t, J = 7.5Hz), 2.62 (2H, q, J = 7Hz), 2.66-2.69 (4H, m), 2.73-2.78 (2H, m), 2.84 (2H, t, J = 6Hz), 2.93 (4H, t, J = 6Hz), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.11-7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1674, 1603, 1494, 1361, 1339, 1243, 1160. 9- (5- [Ethyl [2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5 -On hydrochloride

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N-ethyl- obtained in Reference Example 5 The same operation as in Example 9 was carried out using N- [2- (2-methoxyphenyl) ethyl] amine to obtain the title compound (70 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.07 (3H, t, J = 7 Hz), 1.55-1.62 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m) , 2.56 (2H, t, J = 7.5Hz), 2.62 (2H, q, J = 7Hz), 2.66-2.69 (4H, m), 2.73-2.78 (2H, m), 2.84 (2H, t, J = 6Hz), 2.93 (4H, t, J = 6Hz), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.11-7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1674, 1603, 1494, 1361, 1339, 1243, 1160.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび２-フェニルエチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(123mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.35-1.42 (2H, m), 1.49-1.56 (3H, m), 1.69-1.77 (2H, m), 1.93-1.99 (2H, m), 2.61-2.69 (4H, m), 2.78-2.95 (10H, m), 3.89 (2H, t, J = 6Hz), 7.18-7.31 (5H, m), 7.61 (2H, d, J = 5Hz).IR (フリー塩基; KBr) νcm^-1: 1675, 1604, 1484, 1437, 1362, 1339, 1161. 9- [6-[(2-Phenylethyl) amino] hexanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 2-phenylethylamine obtained in Reference Example 6 The title compound (123 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.35-1.42 (2H, m), 1.49-1.56 (3H, m), 1.69-1.77 (2H, m), 1.93-1.99 (2H, m), 2.61 -2.69 (4H, m), 2.78-2.95 (10H, m), 3.89 (2H, t, J = 6Hz), 7.18-7.31 (5H, m), 7.61 (2H, d, J = 5Hz) .IR ( Free base; KBr) νcm ^-1 : 1675, 1604, 1484, 1437, 1362, 1339, 1161.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび2-(2−メトキシフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(190mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.36-1.44 (2H, m), 1.50-1.57 (3H, m), 1.70-1.77 (2H, m), 1.92-1.99 (2H, m), 2.62-2.69 (4H, m), 2.82-2.85 (6H, m), 2.89-2.96 (4H, m), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.85 (1H, d, J = 8.3Hz), 6.89 (1H, d, J = 7.4Hz), 7.14-7.20 (2H, m), 7.61 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1673, 1603, 1494, 1362, 1339, 1243, 1160. 9- (6-[[2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5- On hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 2- (2 The title compound (190 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -methoxyphenyl) ethylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.36-1.44 (2H, m), 1.50-1.57 (3H, m), 1.70-1.77 (2H, m), 1.92-1.99 (2H, m), 2.62 -2.69 (4H, m), 2.82-2.85 (6H, m), 2.89-2.96 (4H, m), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.85 (1H, d, J = 8.3Hz), 6.89 (1H, d, J = 7.4Hz), 7.14-7.20 (2H, m), 7.61 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1673, 1603, 1494, 1362, 1339, 1243, 1160.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよび2-(2−クロロフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(148mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.37-1.43 (2H, m), 1.51-1.58 (3H, m), 1.71-1.78 (2H, m), 1.95-2.00 (2H, m), 2.65-2.70 (4H, m), 2.84 (2H, t, J = 7.5Hz), 2.86-2.96 (8H, m), 3.89 (2H, t, J = 6Hz), 7.13-7.25 (3H, m), 7.34 (1H, dd, J = 7, 2Hz), 7.61 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1673, 1603, 1483, 1361, 1159. 9- (6-[[2- (2-Chlorophenyl) ethyl] amino] hexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one Hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and 2- (2 The title compound (148 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -chlorophenyl) ethylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.37-1.43 (2H, m), 1.51-1.58 (3H, m), 1.71-1.78 (2H, m), 1.95-2.00 (2H, m), 2.65 -2.70 (4H, m), 2.84 (2H, t, J = 7.5Hz), 2.86-2.96 (8H, m), 3.89 (2H, t, J = 6Hz), 7.13-7.25 (3H, m), 7.34 (1H, dd, J = 7, 2Hz), 7.61 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1673, 1603, 1483, 1361, 1159.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(225mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.37-1.43 (2H, m), 1.51-1.58 (2H, m), 1.71-1.78 (2H, m), 19.3-1.99 (2H, m), 2.30 (3H, s), 2.41 (2H, t, J = 7Hz), 2.58-2.62 (2H, m), 2.67 (2H, t, J = 6Hz), 2.75-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 2.89-2.95 (4H, m), 3.89 (2H, t, J = 6Hz), 7.18-7.29 (5H, m), 7.61 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1676, 1604, 1590, 1484, 1361, 1338, 1161. 9- [6-[(2-Phenylethyl) amino] hexanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N-methyl- obtained in Reference Example 6 The same operation as in Example 9 was performed using N- (2-phenylethyl) amine to give the title compound (225 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.37-1.43 (2H, m), 1.51-1.58 (2H, m), 1.71-1.78 (2H, m), 19.3-1.99 (2H, m), 2.30 (3H, s), 2.41 (2H, t, J = 7Hz), 2.58-2.62 (2H, m), 2.67 (2H, t, J = 6Hz), 2.75-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 2.89-2.95 (4H, m), 3.89 (2H, t, J = 6Hz), 7.18-7.29 (5H, m), 7.61 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1676, 1604, 1590, 1484, 1361, 1338, 1161.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(255mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.36-1.43 (2H, m), 1.51-1.58 (2H, m), 1.71-1.79 (2H, m), 1.93-1.99 (2H, m), 2.32 (3H, s), 2.42 (2H, t, J = 7Hz), 2.55-2.59 (2H, m), 2.67 (2H, t, J = 6Hz), 2.76-2.80 (2H, m), 2.83 (2H, t, J = 6Hz), 2.90-2.95 (4H, m), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 7.61 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1676, 1603, 1589, 1494, 1361, 1243, 1161. 9- (6-[[2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5- On hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N- [2 obtained in Reference Example 6 The title compound (255 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using-(2-methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.36-1.43 (2H, m), 1.51-1.58 (2H, m), 1.71-1.79 (2H, m), 1.93-1.99 (2H, m), 2.32 (3H, s), 2.42 (2H, t, J = 7Hz), 2.55-2.59 (2H, m), 2.67 (2H, t, J = 6Hz), 2.76-2.80 (2H, m), 2.83 (2H, t, J = 6Hz), 2.90-2.95 (4H, m), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m ), 7.61 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1676, 1603, 1589, 1494, 1361, 1243, 1161.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(372mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.35-1.43 (2H, m), 1.51-1.59 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.33 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.68 (2H, t, J = 6Hz), 2.84 (2H, t, J = 6Hz), 2.88-2.99 (6H, m), 3.89 (2H, t, J = 6Hz), 7.11-7.24 (3H, m), 7.32 (1H, d, d, J = 5, 2Hz), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1674, 1604, 1438, 1360, 1299, 1159. 9- [6-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] hexanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline- 5-one hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N- [2 obtained in Reference Example 6 The title compound (372 mg) was obtained as a pale yellow amorphous powder by performing the same operation as in Example 9 using-(2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.35-1.43 (2H, m), 1.51-1.59 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.33 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.68 (2H, t, J = 6Hz), 2.84 (2H, t, J = 6Hz), 2.88 -2.99 (6H, m), 3.89 (2H, t, J = 6Hz), 7.11-7.24 (3H, m), 7.32 (1H, d, d, J = 5, 2Hz), 7.62 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1674, 1604, 1438, 1360, 1299, 1159.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(303mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.36-1.42 (2H, m), 1.49-1.55 (2H, m), 1.70-1.78 (2H, m), 1.93-1.99 (2H, m), 2.29 (3H, s), 2.40 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.68 (2H, t, J = 6Hz), 2.74-2.78 (2H, m), 2.85 (2H, t, J = 6Hz), 2.89-2.96 (4H, m), 3.89 (2H, t, J = 6Hz), 6.86-6.92 (2H, m), 6.97 (1H, d, J = 7.5Hz), 7.20-7.25 (1H, m), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1676, 1604, 1589, 1486, 1361, 1339, 1161. 9- [6-[[2- (3-Fluorophenyl) ethyl] (methyl) amino] hexanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline -5-one hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N- [2 obtained in Reference Example 6 The title compound (303 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using-(3-fluorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.36-1.42 (2H, m), 1.49-1.55 (2H, m), 1.70-1.78 (2H, m), 1.93-1.99 (2H, m), 2.29 (3H, s), 2.40 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.68 (2H, t, J = 6Hz), 2.74-2.78 (2H, m), 2.85 (2H , t, J = 6Hz), 2.89-2.96 (4H, m), 3.89 (2H, t, J = 6Hz), 6.86-6.92 (2H, m), 6.97 (1H, d, J = 7.5Hz), 7.20 -7.25 (1H, m), 7.62 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1676, 1604, 1589, 1486, 1361, 1339, 1161.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-エチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(285mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.05 (3H, t, J = 7Hz), 1.34-1.42 (2H, m), 1.49-1.56 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.50 (2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7Hz), 2.66-2.77 (6H, m), 2.84 (2H,t,J = 6Hz), 2.89-2.95 (4H, m), 3.89 (2H, t, J = 6Hz), 7.16-7.20 (3H, m), 7.25-7.29 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1676, 1603, 1589, 1494, 1361, 1243, 1161. 9- [6- [Ethyl (2-phenylethyl) amino] hexanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N-ethyl- obtained in Reference Example 6 The same operation as in Example 9 was performed using N- (2-phenylethyl) amine to give the title compound (285 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.05 (3H, t, J = 7 Hz), 1.34-1.42 (2H, m), 1.49-1.56 (2H, m), 1.71-1.78 (2H, m) , 1.93-1.99 (2H, m), 2.50 (2H, t, J = 7.5Hz), 2.61 (2H, q, J = 7Hz), 2.66-2.77 (6H, m), 2.84 (2H, t, J = 6Hz), 2.89-2.95 (4H, m), 3.89 (2H, t, J = 6Hz), 7.16-7.20 (3H, m), 7.25-7.29 (2H, m), 7.62 (2H, d, J = 5Hz ).
IR (free base; KBr) νcm ^-1 : 1676, 1603, 1589, 1494, 1361, 1243, 1161.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-エチル-N-[2-(2-メトキシフェニル)エチル]アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(395mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.07 (3H, t, J = 7Hz), 1.37-1.43 (2H, m), 1.51-1.59 (2H, m), 1.72-1.79 (2H, m), 1.93-1.99 (2H, m), 2.52 (2H, t, J = 7.5Hz), 2.62 (2H, q, J = 7Hz), 2.66-2.69 (4H, m), 2.72-2.82 (2H, m), 2.85 (2H, t, J = 6Hz), 2.92 (4H, t, J = 6Hz), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.11-7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; KBr) νcm^-1: 1675, 1603, 1493, 1361, 1242, 1159. 9- (6- [Ethyl [2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5 -On hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N-ethyl- obtained in Reference Example 6 The same operation as in Example 9 was carried out using N- [2- (2-methoxyphenyl) ethyl] amine to obtain the title compound (395 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.07 (3H, t, J = 7 Hz), 1.37-1.43 (2H, m), 1.51-1.59 (2H, m), 1.72-1.79 (2H, m) , 1.93-1.99 (2H, m), 2.52 (2H, t, J = 7.5Hz), 2.62 (2H, q, J = 7Hz), 2.66-2.69 (4H, m), 2.72-2.82 (2H, m) , 2.85 (2H, t, J = 6Hz), 2.92 (4H, t, J = 6Hz), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.11-7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (free base; KBr) νcm ^-1 : 1675, 1603, 1493, 1361, 1242, 1159.

参考例６で得た9-(6-ブロモヘキサノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オンおよびN-イソプロピル-N-[2-(2-メトキシフェニル)エチル]アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物(147mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.00 (6H, d, J = 6.3Hz), 1.36-1.42 (2H, m), 1.48-1.54 (2H, m), 1.71-1.78 (2H, m), 1.93-1.99 (2H, m), 2.47 (2H, t, J = 7.3Hz), 2.57-2.60 (2H, m), 2.65-2.74 (4H, m), 2.82-2.85 (2H, m), 2.89-2.95 (4H, m), 2.98 (1H, q, J = 6.3Hz), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.82-6.88 (2H, m), 7.11-7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (フリー塩基; neat) νcm^-1: 1676, 1604, 1494, 1360, 1243, 1162. 9- (6- [Isopropyl [2- (2-methoxyphenyl) ethyl] amino] hexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5 -On hydrochloride

9- (6-Bromohexanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one and N-isopropyl- obtained in Reference Example 6 The same operation as in Example 9 was performed using N- [2- (2-methoxyphenyl) ethyl] amine to obtain the title compound (147 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.00 (6H, d, J = 6.3 Hz), 1.36-1.42 (2H, m), 1.48-1.54 (2H, m), 1.71-1.78 (2H, m ), 1.93-1.99 (2H, m), 2.47 (2H, t, J = 7.3Hz), 2.57-2.60 (2H, m), 2.65-2.74 (4H, m), 2.82-2.85 (2H, m), 2.89-2.95 (4H, m), 2.98 (1H, q, J = 6.3Hz), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.82-6.88 (2H, m), 7.11- 7.19 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (free base; neat) νcm ^-1 : 1676, 1604, 1494, 1360, 1243, 1162.

参考例７で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(170mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(87mg) を融点175-176℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.58-1.72 (4H, m), 2.18 (3H, s), 2.90-3.05 (8H, m), 3.17 (2H, t, J = 8.5Hz), 3.79 (3H, s), 4.14 (2H, t, J = 8.5Hz), 6.90 (1H, t, J = 7.5Hz), 6.99 (1H, d, J = 7.5Hz), 7.16 (1H, d, J = 7.5Hz), 7.24 (1H, t, J = 8.3Hz), 7.82-7.85 (2H, m), 8.08 (1H, d, J = 8.3Hz), 8.91 (2H, br s).
IR (KBr) νcm^-1: 2955, 2789, 1680, 1661, 1603, 1496, 1441, 1440, 1255. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] amino] -1-pentanone hydrochloride

5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl (170 mg) obtained in Reference Example 7 ) To give the title compound (87 mg) as colorless crystals having a melting point of 175-176 ° C. by a similar operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.58-1.72 (4H, m), 2.18 (3H, s), 2.90-3.05 (8H, m), 3.17 (2H, t, J = 8.5Hz), 3.79 (3H, s), 4.14 (2H, t, J = 8.5Hz), 6.90 (1H, t, J = 7.5Hz), 6.99 (1H, d, J = 7.5Hz), 7.16 (1H, d, J = 7.5Hz), 7.24 (1H, t, J = 8.3Hz), 7.82-7.85 (2H, m), 8.08 (1H, d, J = 8.3Hz), 8.91 (2H, br s).
IR (KBr) νcm ^-1 : 2955, 2789, 1680, 1661, 1603, 1496, 1441, 1440, 1255.

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよび2-(2−メトキシフェニル)エチルアミンを用いて、参考例１および実施例１と同様の操作を順次行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.66 (4H, s), 2.93-3.02 (8H, m), 3.80 (3H, s), 4.69 (2H, s), 6.89-6.94 (1H, m), 6.99-7.07 (2H, m), 7.18 (1H, d, J = 6.3Hz), 7.23-7.28 (1H, m), 7.52 (1H, d, J = 2.1Hz), 7.63 (1H, dd, J = 8.6, 2.1Hz), 8.98 (2H, br s), 10.94 (1H, s).
MS m/z: 383 [M+H]⁺ 6- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

Using Reference Example 1 and 6- (5-Chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 7 The title compound was obtained as a colorless amorphous powder by sequentially performing the same operations as in Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.66 (4H, s), 2.93-3.02 (8H, m), 3.80 (3H, s), 4.69 (2H, s), 6.89-6.94 (1H, m) , 6.99-7.07 (2H, m), 7.18 (1H, d, J = 6.3Hz), 7.23-7.28 (1H, m), 7.52 (1H, d, J = 2.1Hz), 7.63 (1H, dd, J = 8.6, 2.1Hz), 8.98 (2H, br s), 10.94 (1H, s).
MS m / z: 383 [M + H] ⁺

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および2,3,4,5-テトラヒドロ-1H-2-ベンズアゼピン(332mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(407mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.45-1.80 (6H, m), 2.39 (2H, t, J = 7.4Hz), 2.71 (2H, t, J = 7.6Hz), 2.80-3.30 (10H, m), 3.88 (2H, s), 4.12 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.65 (1H, s), 7.69 (1H, s). 8- [5- (1,3,4,5-Tetrahydro-2H-2-benzazepin-2-yl) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij ] Quinolin-4-one

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and 2,3 obtained in Reference Example 1 , 4,5-Tetrahydro-1H-2-benzazepine (332 mg) was used in the same manner as in Example 9 to obtain the title compound (407 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.45-1.80 (6H, m), 2.39 (2H, t, J = 7.4 Hz), 2.71 (2H, t, J = 7.6 Hz), 2.80-3.30 ( 10H, m), 3.88 (2H, s), 4.12 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.65 (1H, s), 7.69 (1H, s).

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および7-メトキシ-2,3,4,5-テトラヒドロ-1H-2-ベンズアゼピン(304mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(294mg) を融点167-168℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.45-1.80 (6H, m), 2.38 (2H, t, J = 7.4Hz), 2.71 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.21 (2H, t, J = 8.4Hz), 3.78 (3H, s), 3.84 (2H, s), 4.13 (2H, t, J = 8.4Hz), 6.61 (1H, dd, J = 8.0, 2.6Hz), 6.69 (1H, d, J = 2.6Hz), 7.02 (1H, d, J = 8.4Hz), 7.66 (1H, s), 7.70 (1H, s). 8- [5- (7-methoxy-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2, 1-ij] quinolin-4-one hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 7-methoxy obtained in Reference Example 1 The title compound (294 mg) was obtained as colorless crystals having a melting point of 167-168 ° C. by carrying out the same operation as in Example 9 using -2,3,4,5-tetrahydro-1H-2-benzazepine (304 mg). Obtained.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.45-1.80 (6H, m), 2.38 (2H, t, J = 7.4 Hz), 2.71 (2H, t, J = 7.6 Hz), 2.80-3.15 ( 8H, m), 3.21 (2H, t, J = 8.4Hz), 3.78 (3H, s), 3.84 (2H, s), 4.13 (2H, t, J = 8.4Hz), 6.61 (1H, dd, J = 8.0, 2.6Hz), 6.69 (1H, d, J = 2.6Hz), 7.02 (1H, d, J = 8.4Hz), 7.66 (1H, s), 7.70 (1H, s).

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2,3,4,5-テトラヒドロ-1H-2-ベンズアゼピン(252mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(463mg) を融点195-197℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.25-1.85 (8H, m), 2.35 (2H, t, J = 7.4Hz), 2.71 (2H, t, J = 7.6Hz), 2.80-3.00 (4H, m), 3.02 (2H, t, J = 7.6Hz), 3.11 (2H, t, J = 5.4Hz), 3.22 (2H, t, J = 8.4Hz), 3.88 (2H, s), 4.13 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.66 (1H, s), 7.70 (1H, s).
元素分析 C₂₇H₃₂N₂O₂・HClとして
計算値：C, 70.58; H, 7.34; N, 6.18.
実験値：C, 70.16; H, 7.32; N, 6.08. 8- [6- (1,3,4,5-Tetrahydro-2H-2-benzazepin-2-yl) hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij ] Quinolin-4-one hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 2,3 obtained in Reference Example 2 , 4,5-Tetrahydro-1H-2-benzazepine (252 mg) was used in the same manner as in Example 9 to obtain the title compound (463 mg) as colorless crystals having a melting point of 195-197 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.25-1.85 (8H, m), 2.35 (2H, t, J = 7.4 Hz), 2.71 (2H, t, J = 7.6 Hz), 2.80-3.00 ( 4H, m), 3.02 (2H, t, J = 7.6Hz), 3.11 (2H, t, J = 5.4Hz), 3.22 (2H, t, J = 8.4Hz), 3.88 (2H, s), 4.13 ( 2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.66 (1H, s), 7.70 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₂ N ₂ O ₂ .HCl: C, 70.58; H, 7.34; N, 6.18.
Experimental value: C, 70.16; H, 7.32; N, 6.08.

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および7-メトキシ-2,3,4,5-テトラヒドロ-1H-2-ベンズアゼピン(253mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(366mg) を淡黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.24-1.80 (8H, m), 2.34 (2H, t, J = 7.4Hz), 2.71 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.22 (2H, t, J = 8.4Hz), 3.78 (3H, s), 3.84 (2H, s), 4.13 (2H, t, J = 8.4Hz), 6.61 (1H, dd, J = 8.0, 2.6Hz), 6.69 (1H, d, J = 2.6Hz), 7.02 (1H, d, J = 8.4Hz), 7.66
(1H, s), 7.70 (1H, s). 8- [6- (7-methoxy-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl) hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2, 1-ij] quinolin-4-one hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 7-methoxy obtained in Reference Example 2 The title compound (366 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -2,3,4,5-tetrahydro-1H-2-benzazepine (253 mg). .
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.24-1.80 (8H, m), 2.34 (2H, t, J = 7.4 Hz), 2.71 (2H, t, J = 7.6 Hz), 2.80-3.15 ( 8H, m), 3.22 (2H, t, J = 8.4Hz), 3.78 (3H, s), 3.84 (2H, s), 4.13 (2H, t, J = 8.4Hz), 6.61 (1H, dd, J = 8.0, 2.6Hz), 6.69 (1H, d, J = 2.6Hz), 7.02 (1H, d, J = 8.4Hz), 7.66
(1H, s), 7.70 (1H, s).

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) およびイソインドリン(269mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(191mg) を融点219-221℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.60-1.95 (4H, m), 2.60-2.80 (4H, m), 2.90-3.05 (4H, m), 3.19 (2H, t, J = 8.4Hz), 3.92 (4H, s), 4.12 (2H, t, J = 8.4Hz), 7.10 (4H, s), 7.69 (1H, s), 7.73 (1H, s). 8- [5- (1,3-Dihydro-2H-isoindol-2-yl) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and isoindoline (600 mg) obtained in Reference Example 1 The title compound (191 mg) was obtained as colorless crystals having a melting point of 219-221 ° C. by carrying out the same operation as in Example 9 using 269 mg).
¹ H NMR (free _{base; 200MHz, CDCl 3) δ 1.60-1.95} (4H, m), 2.60-2.80 (4H, m), 2.90-3.05 (4H, m), 3.19 (2H, t, J = 8.4Hz ), 3.92 (4H, s), 4.12 (2H, t, J = 8.4Hz), 7.10 (4H, s), 7.69 (1H, s), 7.73 (1H, s).

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および炭酸カリウム(500mg) のアセトニトリル(10ml) 懸濁液に(2-ブロモエチル)ベンゼン(0.22ml) を室温にて滴下した。室温で12時間攪拌後、反応液を減圧下濃縮した。残査に水(15ml)および酢酸エチル(20ml)を加え、酢酸エチルで抽出した。抽出液を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル−メタノール(9:1))にて精製し、表題化合物のフリー塩基体を淡黄色油状物(617mg)として得た。
¹H NMR(200MHz, CDCl₃) δ 1.20-1.50(3H, m), 1.60-1.85(4H, m), 1.90-2.10(2H, m), 2.50-3.10(12H, m), 3.21(2H, t, J = 8.4Hz), 4.12(2H, t, J = 8.4Hz), 7.10-7.35(5H, m), 7.68(1H, s), 7.72(1H, s).
上記フリー塩基体(610mg) のエタノール溶液を１当量以上の塩化水素（酢酸エチル溶液）で処理し、表題化合物を融点219-221℃の無色結晶として得た。
元素分析 C₂₇H₃₂N₂O₂・HClとして
計算値：C, 71.58; H, 7.34; N, 6.18.
実験値：C, 71.27; H, 7.13; N, 6.20. 8- [3- [1- (2-Phenylethyl) -4-piperidinyl] propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

Of 8- [3- (4-piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and potassium carbonate (500 mg) To a suspension of acetonitrile (10 ml), (2-bromoethyl) benzene (0.22 ml) was added dropwise at room temperature. After stirring at room temperature for 12 hours, the reaction solution was concentrated under reduced pressure. Water (15 ml) and ethyl acetate (20 ml) were added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; ethyl acetate-methanol (9: 1)) to obtain the free base of the title compound as a pale yellow oil (617 mg).
¹ H NMR (200 MHz, CDCl ₃ ) δ 1.20-1.50 (3H, m), 1.60-1.85 (4H, m), 1.90-2.10 (2H, m), 2.50-3.10 (12H, m), 3.21 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.10-7.35 (5H, m), 7.68 (1H, s), 7.72 (1H, s).
The ethanol solution of the above free base (610 mg) was treated with 1 equivalent or more of hydrogen chloride (ethyl acetate solution) to obtain the title compound as colorless crystals having a melting point of 219-221 ° C.
Elemental analysis Calculated as C ₂₇ H ₃₂ N ₂ O ₂ .HCl: C, 71.58; H, 7.34; N, 6.18.
Experimental value: C, 71.27; H, 7.13; N, 6.20.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および1-(2-ブロモエチル)-2-メチルベンゼン(432mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(624mg) を融点215-216℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.25-1.50 (3H, m), 1.55-1.85 (4H, m), 1.90-2.20 (2H, m), 2.33 (3H, s), 2.45-2.60 (2H, m), 2.65-3.10 (10H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.13 (4H, s), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₈H₃₄N₂O₂・HCl・0.5H₂Oとして
計算値：C, 70.64; H, 7.62; N, 5.88.
実験値：C, 70.24; H, 7.66; N, 5.81. 8- (3- [1- [2- (2-Methylphenyl) ethyl] -4-piperidinyl] propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and 1- (2-bromoethyl ) -2-Methylbenzene (432 mg) was used in the same manner as in Example 81 to obtain the title compound (624 mg) as colorless crystals having a melting point of 215 to 216 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.25-1.50 (3H, m), 1.55-1.85 (4H, m), 1.90-2.20 (2H, m), 2.33 (3H, s), 2.45-2.60 (2H, m), 2.65-3.10 (10H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.13 (4H, s), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₈ H ₃₄ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 70.64; H, 7.62; N, 5.88.
Experimental values: C, 70.24; H, 7.66; N, 5.81.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および1-(2-ブロモエチル)-2-フルオロベンゼン(367mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(380mg) を融点210-212℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.55-2.10 (6H, m), 2.50-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 6.95-7.30 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₁FN₂O₂・HCl・0.5H₂Oとして
計算値：C, 67.56; H, 6.93; N, 5.84.
実験値：C, 67.92; H, 6.68; N, 5.79. 8- (3- [1- [2- (2-Fluorophenyl) ethyl] -4-piperidinyl] propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and 1- (2-bromoethyl ) -2-Fluorobenzene (367 mg) was used in the same manner as in Example 81 to give the title compound (380 mg) as colorless crystals having a melting point of 210-212 ° C.
¹ H NMR (free _{base; 200MHz, CDCl 3) δ 1.20-1.45} (3H, m), 1.55-2.10 (6H, m), 2.50-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz ), 4.14 (2H, t, J = 8.4Hz), 6.95-7.30 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₁ FN ₂ O ₂ · HCl · 0.5H ₂ O: C, 67.56; H, 6.93; N, 5.84.
Experimental value: C, 67.92; H, 6.68; N, 5.79.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および1-(2-ブロモエチル)-3-フルオロベンゼン(367mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(351mg) を融点225-227℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.20-1.50 (3H, m), 1.60-1.85 (4H, m), 1.90-2.10 (2H, m), 2.50-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m), 7.15-7.30 (1H, m), 7.68 (1H, s), 7.72 (1H, s). 8- (3- [1- [2- (3-Fluorophenyl) ethyl] -4-piperidinyl] propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 1- (2-bromoethyl ) -3-Fluorobenzene (367 mg) was used in the same manner as in Example 81 to obtain the title compound (351 mg) as colorless crystals having a melting point of 225-227 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.50 (3H, m), 1.60-1.85 (4H, m), 1.90-2.10 (2H, m), 2.50-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 6.80-7.00 (3H, m), 7.15-7.30 (1H, m), 7.68 (1H, s), 7.72 ( 1H, s).

8-[3-(4-ピペリジニル)プロパノCル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および1-(2-ブロモエチル)-3-クロロベンゼン(394mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(369mg) を融点223-225℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.20-1.50 (3H, m), 1.60-1.85 (4H, m), 1.90-2.10 (2H, m), 2.45-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.00-7.30 (4H, m), 7.68 (1H, s), 7.73 (1H, s).
元素分析 C₂₇H₃₁ClN₂O₂・HCl・H₂Oとして
計算値：C, 64.16; H, 6.78; N, 5.54.
実験値：C, 63.92; H, 6.75; N, 5.52. 8- (3- [1- [2- (3-chlorophenyl) ethyl] -4-piperidinyl] propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- 4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 1- (2 -Bromoethyl) -3-chlorobenzene (394 mg) was used in the same manner as in Example 81 to obtain the title compound (369 mg) as colorless crystals having a melting point of 223-225 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.50 (3H, m), 1.60-1.85 (4H, m), 1.90-2.10 (2H, m), 2.45-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.00-7.30 (4H, m), 7.68 (1H, s), 7.73 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₁ ClN ₂ O ₂ · HCl · H ₂ O: C, 64.16; H, 6.78; N, 5.54.
Experimental value: C, 63.92; H, 6.75; N, 5.52.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) およびメタンスルホン酸2,3-ジヒドロ-1H-インデン-2-イル(428mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(326mg) を融点290℃(分解)の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.10-1.40 (3H, m), 1.45-1.80 (4H, m), 1.85-2.00 (2H, m), 2.61 (2H, t, J = 7.6Hz), 2.70-3.20 (13H, m), 4.03 (2H, t, J = 8.4Hz), 7.00-7.15 (4H, m), 7.57 (1H, s), 7.62 (1H, s).
元素分析 C₂₈H₃₂N₂O₂・HCl・0.5H₂Oとして
計算値：C, 70.94; H, 7.23; N, 5.91.
実験値：C, 71.19; H, 6.97; N, 5.71. 8- [3- [1- (2,3-Dihydro-1H-inden-2-yl) -4-piperidinyl] propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1 -ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and methanesulfonic acid 2,3 The title compound (326 mg) was obtained as colorless crystals having a melting point of 290 ° C. (decomposition) by conducting the same operation as in Example 81 using -dihydro-1H-inden-2-yl (428 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.10-1.40 (3H, m), 1.45-1.80 (4H, m), 1.85-2.00 (2H, m), 2.61 (2H, t, J = 7.6 Hz ), 2.70-3.20 (13H, m), 4.03 (2H, t, J = 8.4Hz), 7.00-7.15 (4H, m), 7.57 (1H, s), 7.62 (1H, s).
Elemental analysis Calculated as C ₂₈ H ₃₂ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 70.94; H, 7.23; N, 5.91.
Experimental values: C, 71.19; H, 6.97; N, 5.71.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および(3-ブロモプロピル)ベンゼン(0.245ml) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(488mg) を融点173-175℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.60-2.00 (8H, m), 2.35 (2H, t, J = 7.6Hz), 2.61 (2H, t, J = 8.0Hz), 2.70 (2H, t, J = 8.4Hz), 2.80-2.95 (4H, m), 3.01 (2H, t, J = 8.0Hz), 3.21 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.05-7.35 (5H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₈H₃₄N₂O₂・HClとして
計算値：C, 72.01; H, 7.55; N, 6.00.
実験値：C, 71.68; H, 7.50; N, 5.73. 8- [3- [1- (3-Phenylpropyl) -4-piperidinyl] propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and (3-bromopropyl) The title compound (488 mg) was obtained as colorless crystals having a melting point of 173 to 175 ° C. by carrying out the same operation as in Example 81 using benzene (0.245 ml).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.60-2.00 (8H, m), 2.35 (2H, t, J = 7.6 Hz), 2.61 (2H, t, J = 8.0Hz), 2.70 (2H, t, J = 8.4Hz), 2.80-2.95 (4H, m), 3.01 (2H, t, J = 8.0Hz), 3.21 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.05-7.35 (5H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis Calculated as C ₂₈ H ₃₄ N ₂ O ₂ .HCl: C, 72.01; H, 7.55; N, 6.00.
Experimental values: C, 71.68; H, 7.50; N, 5.73.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および(2-ブロモエトキシ)ベンゼン(0.222ml) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(190mg) を無色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.60-1.85 (4H, m), 2.00-2.25 (2H, m), 2.71 (2H, t, J = 7.6Hz), 2.80 (2H, t, J = 6.2Hz), 2.85-3.10 (6H, m), 3.22 (2H, t, J = 8.4Hz), 4.00-4.20 (4H, m), 6.85-7.00 (3H, m), 7.20-7.35 (2H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₇H₃₂N₂O₃・HCl・0.5H₂Oとして
計算値：C, 67.84; H, 7.17; N, 5.86.
実験値：C, 68.10; H, 7.22; N, 5.83. 8- [3- [1- (2-phenoxyethyl) -4-piperidinyl] propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and (2-bromoethoxy) The title compound (190 mg) was obtained as a colorless amorphous powder by conducting the same operation as in Example 81 using benzene (0.222 ml).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.60-1.85 (4H, m), 2.00-2.25 (2H, m), 2.71 (2H, t, J = 7.6 Hz ), 2.80 (2H, t, J = 6.2Hz), 2.85-3.10 (6H, m), 3.22 (2H, t, J = 8.4Hz), 4.00-4.20 (4H, m), 6.85-7.00 (3H, m), 7.20-7.35 (2H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis _{C 27 H 32 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 67.84; H, 7.17 ; N, 5.86.
Experimental value: C, 68.10; H, 7.22; N, 5.83.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および1-(2-ブロモエトキシ)-2-エトキシベンゼン(412mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(583mg) を無色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.20-1.50 (6H, m), 1.60-1.80 (4H, m), 2.00-2.25 (2H, m), 2.71 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.22 (2H, t, J = 8.4Hz), 4.00-4.20 (6H, m), 6.85-6.95 (4H, m), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₉H₃₆N₂O₄・HCl・0.5H₂Oとして
計算値：C, 66.72; H, 7.34; N, 5.37.
実験値：C, 66.75; H, 7.26; N, 5.28. 8- (3- [1- [2- (2-Ethoxyphenoxy) ethyl] -4-piperidinyl] propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 1- (2-bromo The title compound (583 mg) was obtained as a colorless amorphous powder by the same procedure as in Example 81 using ethoxy) -2-ethoxybenzene (412 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.50 (6H, m), 1.60-1.80 (4H, m), 2.00-2.25 (2H, m), 2.71 (2H, t, J = 7.6 Hz ), 2.80-3.15 (8H, m), 3.22 (2H, t, J = 8.4Hz), 4.00-4.20 (6H, m), 6.85-6.95 (4H, m), 7.67 (1H, s), 7.72 ( 1H, s).
Elemental analysis Calculated as C ₂₉ H ₃₆ N ₂ O ₄ · HCl · 0.5H ₂ O: C, 66.72; H, 7.34; N, 5.37.
Experimental value: C, 66.75; H, 7.26; N, 5.28.

参考例９で得た5-(5-クロロペンタノイル)-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点234-235℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.68-1.79 (4H, m), 2.83 (3H, d, J = 4.8Hz), 3.04-3.30 (8H, m), 7.03 (1H, d, J = 8.4Hz), 7.31-7.50 (5H, m), 7.69 (1H, dd, J = 8.3, 1.7Hz), 10.46 (1H, br s), 10.96 (1H, s), 11.10 (1H, s).
元素分析 C₂₁H₂₄ClN₃O₂・HCl・0.5H₂Oとして
計算値：C, 58.47; H, 6.08; N, 9.74.
実験値：C, 58.49; H, 6.05; N, 9.51.
MS m/z: 386 [M+H]⁺ 5- [5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Using 5- (5-chloropentanoyl) -1,3-dihydro-2H-benzimidazol-2-one and N- [2- (2-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 9 The title compound was obtained as colorless crystals having the melting point of 234-235 ° C. by carrying out the same operation as in Example 9.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.68-1.79 (4H, m), 2.83 (3H, d, J = 4.8Hz), 3.04-3.30 (8H, m), 7.03 (1H, d, J = 8.4Hz), 7.31-7.50 (5H, m), 7.69 (1H, dd, J = 8.3, 1.7Hz), 10.46 (1H, br s), 10.96 (1H, s), 11.10 (1H, s).
Elemental analysis Calculated as C ₂₁ H ₂₄ ClN ₃ O ₂ · HCl · 0.5H ₂ O: C, 58.47; H, 6.08; N, 9.74.
Experimental value: C, 58.49; H, 6.05; N, 9.51.
MS m / z: 386 [M + H] ⁺

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点142-143℃の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.64-1.83 (4H, m), 2.42 (3H, s), 2.54-2.74 (4H, m), 2.93-3.02 (4H, m), 3.46 (3H, s), 3.47 (3H, s), 6.99 (1H, d, J = 8.4Hz), 7.13-7.35 (4H, m), 7.63 (1H, d, J = 1.2Hz), 7.79 (1H, dd, J = 8.2, 1.6Hz).
MS m/z: 414 [M+H]⁺ 5- [5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one and N- [2- (2-chlorophenyl) ethyl]-obtained in Reference Example 10 The same operation as in Example 9 was performed using N-methylamine to give the title compound as colorless crystals with a melting point of 142-143 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.64-1.83 (4H, m), 2.42 (3H, s), 2.54-2.74 (4H, m), 2.93-3.02 (4H, m), 3.46 (3H , s), 3.47 (3H, s), 6.99 (1H, d, J = 8.4Hz), 7.13-7.35 (4H, m), 7.63 (1H, d, J = 1.2Hz), 7.79 (1H, dd, J = 8.2, 1.6Hz).
MS m / z: 414 [M + H] ⁺

参考例４８で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(280mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(220mg) を無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.60-1.73(4H, m), 2.18(3H, s), 2.90-3.01(6H, m), 3.05-3.10(2H, m), 3.16(2H, t, J = 8.4Hz), 4.13(2H, t, J = 8.4Hz), 7.21-7.34(5H, m), 7.81(1H, s), 7.82(1H, d, J = 8Hz), 8.08(1H, t, J = 8Hz), 9.21(2H, br.s).
IR (KBr) νcm^-1: 3438, 2783, 1679, 1662, 1604, 1495, 1440, 1401, 1334, 1260. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -5-[(2-phenylethyl) amino] -1-pentanone hydrochloride

Using tert-butyl 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl (2-phenylethyl) carbamate (280 mg) obtained in Reference Example 48, The title compound (220 mg) was obtained as colorless crystals by the same operation as in Example 1.
¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.60-1.73 (4H, m), 2.18 (3H, s), 2.90-3.01 (6H, m), 3.05-3.10 (2H, m), 3.16 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.21-7.34 (5H, m), 7.81 (1H, s), 7.82 (1H, d, J = 8Hz), 8.08 (1H , t, J = 8Hz), 9.21 (2H, br.s).
IR (KBr) νcm ^-1 : 3438, 2783, 1679, 1662, 1604, 1495, 1440, 1401, 1334, 1260.

参考例４９で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(330mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(175mg) を融点185-186℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.63-1.74(4H, m), 2.17(3H, s), 2.92-3.01(4H, m), 3.08-3.18(6H, m), 4.13(2H, t, J = 8Hz), 7.26-7.34(2H, m), 7.39(1H, d, d, J = 7, 2Hz), 7.44(1H, d, d, J = 7, 2Hz), 7.81(1H, s), 7.82(1H, d, J = 8Hz), 8.07(1H, d, J = 8Hz), 9.35(2H, s).
IR (KBr) νcm^-1: 3434, 2947, 2782, 1683, 1660, 1441, 1403, 1335, 1259. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -5-[[2- (2-chlorophenyl) ethyl] amino] -1-pentanone hydrochloride

Tert-Butyl 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate obtained in Reference Example 49 (330 mg) The title compound (175 mg) was obtained as colorless crystals with a melting point of 185-186 ° C. by carrying out the same operation as in Example 1 using
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.63-1.74 (4H, m), 2.17 (3H, s), 2.92-3.01 (4H, m), 3.08-3.18 (6H, m), 4.13 (2H, t, J = 8Hz), 7.26-7.34 (2H, m), 7.39 (1H, d, d, J = 7, 2Hz), 7.44 (1H, d, d, J = 7, 2Hz), 7.81 (1H, s), 7.82 (1H, d, J = 8Hz), 8.07 (1H, d, J = 8Hz), 9.35 (2H, s).
IR (KBr) νcm ^-1 : 3434, 2947, 2782, 1683, 1660, 1441, 1403, 1335, 1259.

参考例５０で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(452mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(330mg) を融点164-165℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.58-1.72(4H, m), 2.93(6H, t, J = 7Hz), 2.99-3.03(2H, m), 3.05(2H, t, J = 8.2Hz), 3.60(2H, t, J = 8.2Hz), 3.78(3H, s), 6.81(1H, d, J = 8Hz), 6.89(1H, t, J = 7Hz), 6.98(1H, d, J = 7Hz), 7.17(1H, d, J = 7Hz), 7.24(1H, t, J = 7Hz), 7.74(1H, d, J = 8Hz), 7.75(1H, s), 9.06(4H, br.s).
IR (KBr) νcm^-1: 3429, 2950, 2781, 2460, 1694, 1497, 1247. 1- (2,3-Dihydro-1H-indol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] amino] -1-pentanone dihydrochloride

Using tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate (452 mg) obtained in Reference Example 50 The title compound (330 mg) was obtained as colorless crystals having a melting point of 164-165 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.58-1.72 (4H, m), 2.93 (6H, t, J = 7Hz), 2.99-3.03 (2H, m), 3.05 (2H, t, J = 8.2 Hz), 3.60 (2H, t, J = 8.2Hz), 3.78 (3H, s), 6.81 (1H, d, J = 8Hz), 6.89 (1H, t, J = 7Hz), 6.98 (1H, d, J = 7Hz), 7.17 (1H, d, J = 7Hz), 7.24 (1H, t, J = 7Hz), 7.74 (1H, d, J = 8Hz), 7.75 (1H, s), 9.06 (4H, br .s).
IR (KBr) νcm ^-1 : 3429, 2950, 2781, 2460, 1694, 1497, 1247.

参考例５１で得た5-(2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(120mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(106mg) を融点150-151℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.60-1.67(4H, m), 2.80(3H, s), 2.85-3.01(10H, m), 3.44(2H, t, J = 8.4Hz), 3.78(3H, s), 6.46(1H, d, J = 8.3Hz), 6.89(1H, t, J = 7.4Hz), 6.98(1H, d, J = 8.3Hz), 7.16(1H, d, J = 7.4Hz), 7.23(1H, t, J = 8.3Hz), 7.60(1H, s), 7.72(1H, d, J = 8.3Hz), 9.10(3H, br.s).
IR (KBr) νcm^-1: 3436, 2583, 2424, 1675, 1600, 1494, 1464, 1249, 1032, 760. 1- (2,3-Dihydro-1H-indol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] amino] -1-pentanone dihydrochloride

Using tert-butyl 5- (2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate (120 mg) obtained in Reference Example 51 The title compound (106 mg) was obtained as colorless crystals having a melting point of 150-151 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.60-1.67 (4H, m), 2.80 (3H, s), 2.85-3.01 (10H, m), 3.44 (2H, t, J = 8.4Hz), 3.78 (3H, s), 6.46 (1H, d, J = 8.3Hz), 6.89 (1H, t, J = 7.4Hz), 6.98 (1H, d, J = 8.3Hz), 7.16 (1H, d, J = 7.4Hz), 7.23 (1H, t, J = 8.3Hz), 7.60 (1H, s), 7.72 (1H, d, J = 8.3Hz), 9.10 (3H, br.s).
IR (KBr) νcm ^-1 : 3436, 2583, 2424, 1675, 1600, 1494, 1464, 1249, 1032, 760.

参考例５２で得た5-(1-エチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(165mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(145mg) を融点131-133℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.08(3H, t, J = 7.2Hz), 1.61-1.69(4H, m), 2.84-3.01(10H, m), 3.23(2H, q, J = 7.2Hz), 3.48(2H, t, J = 8.4Hz), 3.78(3H, s), 6.45(1H, d, J = 8.4Hz), 6.89(1H, t, J = 7Hz), 6.98(1H, d, J = 8.4Hz), 7.16(1H, d, J = 7Hz), 7.23(1H, t, J = 8.4Hz), 7.59(1H, s), 7.70(1H, d, J = 8.4Hz), 9.11(3H, br).
IR (KBr) νcm^-1: 3426, 2777, 2458, 1697, 1602, 1496, 1442, 1317, 1248, 1051, 763. 1- (1-Ethyl-2,3-dihydro-1H-indol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] amino] -1-pentanone dihydrochloride

Tert-butyl 5- (1-ethyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 52 (165 mg ) To give the title compound (145 mg) as colorless crystals with a melting point of 131-133 ° C. by a similar operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.08 (3H, t, J = 7.2Hz), 1.61-1.69 (4H, m), 2.84-3.01 (10H, m), 3.23 (2H, q, J = 7.2Hz), 3.48 (2H, t, J = 8.4Hz), 3.78 (3H, s), 6.45 (1H, d, J = 8.4Hz), 6.89 (1H, t, J = 7Hz), 6.98 (1H, d, J = 8.4Hz), 7.16 (1H, d, J = 7Hz), 7.23 (1H, t, J = 8.4Hz), 7.59 (1H, s), 7.70 (1H, d, J = 8.4Hz), 9.11 (3H, br).
IR (KBr) νcm ^-1 : 3426, 2777, 2458, 1697, 1602, 1496, 1442, 1317, 1248, 1051, 763.

参考例５３で得た5-[1-(3-ヒドロキシプロピル)-2,3-ジヒドロ-1H-インドール-5-イル]-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(60mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(55mg) を淡黄色非晶状粉末として得た。
¹H NMR(400MHz, CD₃OD) δ 1.68-1.79(4H, m), 1.84(2H, t, J = 7.4Hz), 1.90-1.99(2H, m), 2.92-3.18(8H, m), 3.35(2H, t, J = 6Hz), 3.57-3.70(4H, m), 3.82(3H, s), 4.82(4H, s), 6.63(1H, d, J = 8Hz), 6.88(1H, t, J = 7Hz), 6.95(1H, d, J = 8Hz), 7.16(1H, d, J = 7.4Hz), 7.23(1H, t, J = 7.4Hz), 7.69(1H, s), 7.79(1H, d, J = 7Hz).
IR (neat) νcm^-1: 3402, 2920, 1693, 1602, 1496, 1443, 1247, 760. 1- [1- (3-Hydroxypropyl) -2,3-dihydro-1H-indol-5-yl] -5-[[2- (2-methoxyphenyl) ethyl] amino] -1-pentanone dihydrochloride

5- [1- (3-Hydroxypropyl) -2,3-dihydro-1H-indol-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamic acid obtained in Reference Example 53 The same operation as in Example 1 was carried out using tert-butyl (60 mg) to obtain the title compound (55 mg) as a pale yellow amorphous powder.
¹ H NMR (400MHz, CD ₃ OD) δ 1.68-1.79 (4H, m), 1.84 (2H, t, J = 7.4Hz), 1.90-1.99 (2H, m), 2.92-3.18 (8H, m), 3.35 (2H, t, J = 6Hz), 3.57-3.70 (4H, m), 3.82 (3H, s), 4.82 (4H, s), 6.63 (1H, d, J = 8Hz), 6.88 (1H, t , J = 7Hz), 6.95 (1H, d, J = 8Hz), 7.16 (1H, d, J = 7.4Hz), 7.23 (1H, t, J = 7.4Hz), 7.69 (1H, s), 7.79 ( (1H, d, J = 7Hz).
IR (neat) νcm ^-1 : 3402, 2920, 1693, 1602, 1496, 1443, 1247, 760.

参考例５４で得た[5-(5-[(tert-ブトキシカルボニル)[2-(2-メトキシフェニル)エチル]アミノ]ペンタノイル)-2,3-ジヒドロ-1H-インドール-1-イル]酢酸エチル(270mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(255mg) を淡黄色非晶状粉末として得た。
¹H NMR(400MHz, CD₃OD) δ 1.26(3H, t, J = 7Hz), 1.70-1.80(4H, m), 2.96-3.21(10H, m), 3.82-3.85(2H, m), 3.81(3H, s), 3.86(2H, s), 4.18(2H, q, J = 7.2Hz), 4.84(3H, s), 6.37(1H, d, J = 8.34Hz), 6.91(1H, t, J = 7.4Hz), 6.98(1H, d, J = 8.3Hz), 7.20(1H, d, J = 7.4Hz), 7.26(1H, t, J = 8.3Hz), 7.68(1H, s), 7.76(1H, d, J = 8.3Hz).
IR (KBr) νcm^-1: 3420, 2774, 1736, 1663, 1603, 1496, 1443, 1248, 1182, 1026, 759. [5- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -2,3-dihydro-1H-indol-1-yl] ethyl acetate dihydrochloride

[5- (5-[(tert-Butoxycarbonyl) [2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -2,3-dihydro-1H-indol-1-yl] acetic acid obtained in Reference Example 54 The title compound (255 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 1 using ethyl (270 mg).
¹ H NMR (400MHz, CD ₃ OD) δ 1.26 (3H, t, J = 7Hz), 1.70-1.80 (4H, m), 2.96-3.21 (10H, m), 3.82-3.85 (2H, m), 3.81 (3H, s), 3.86 (2H, s), 4.18 (2H, q, J = 7.2Hz), 4.84 (3H, s), 6.37 (1H, d, J = 8.34Hz), 6.91 (1H, t, J = 7.4Hz), 6.98 (1H, d, J = 8.3Hz), 7.20 (1H, d, J = 7.4Hz), 7.26 (1H, t, J = 8.3Hz), 7.68 (1H, s), 7.76 (1H, d, J = 8.3Hz).
IR (KBr) νcm ^-1 : 3420, 2774, 1736, 1663, 1603, 1496, 1443, 1248, 1182, 1026, 759.

参考例５５で得た5-[1-[(エチルアミノ)カルボニル]-2,3-ジヒドロ-1H-インドール-5-イル]-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(250mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(205mg) を融点185-186℃の無色結晶として得た
¹H NMR(400MHz, DMSO-d₆) δ 1.08(3H, t, J = 7.3Hz), 1.63-1.70(4H, m), 2.92-3.03(8H, m), 3.11-3.18(4H, m), 3.79(3H, s), 3.93(2H, t, J = 8.4Hz), 6.87-6.91(2H, m), 6.98(1H, d, J = 8.4Hz), 7.16(1H, d, J = 7.4Hz), 7.24(1H, t, J = 8.4Hz), 7.73(1H, s), 7.76(1H, d, J = 8.4Hz), 7.88(1H, d, J = 8.4Hz), 9.06(2H, s).
IR (KBr) νcm^-1: 3315, 2773, 1667, 1604, 1526, 1494, 1442, 1319, 1245, 754. N-ethyl-5- (5-[[2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -1-indolinecarboxamide hydrochloride

5- [1-[(Ethylamino) carbonyl] -2,3-dihydro-1H-indol-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamine obtained in Reference Example 55 The title compound (205 mg) was obtained as colorless crystals having a melting point of 185-186 ° C. by conducting the same operation as in Example 1 using tert-butyl acid (250 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.08 (3H, t, J = 7.3Hz), 1.63-1.70 (4H, m), 2.92-3.03 (8H, m), 3.11-3.18 (4H, m) , 3.79 (3H, s), 3.93 (2H, t, J = 8.4Hz), 6.87-6.91 (2H, m), 6.98 (1H, d, J = 8.4Hz), 7.16 (1H, d, J = 7.4 Hz), 7.24 (1H, t, J = 8.4Hz), 7.73 (1H, s), 7.76 (1H, d, J = 8.4Hz), 7.88 (1H, d, J = 8.4Hz), 9.06 (2H, s).
IR (KBr) νcm ^-1 : 3315, 2773, 1667, 1604, 1526, 1494, 1442, 1319, 1245, 754.

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.54-1.61(2H, m), 1.70-1.78(2H, m), 2.25(3H, s), 2.31(3H, s), 2.46(2H, t, J = 7.5Hz), 2.55-2.59(2H, m), 2.76-2.80(2H, m), 2.94(2H, t, J = 7.3Hz), 3.23(2H, t, J = 8.3Hz), 3.81(3H, s), 4.11(2H, t, J = 8.3Hz), 6.82-6.87(2H, m), 7.12-7.19(2H, m), 7.81-7.84(2H, m), 8.23(1H, d, J = 8.3Hz).
IR (フリー塩基; neat)νcm^-1: 1673, 1603, 1493, 1440, 1394, 1329, 1244. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] -1-pentanone hydrochloride

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one and N- [2- (2-methoxyphenyl) ethyl] obtained in Reference Example 11 The title compound was obtained as a yellow amorphous powder by the same procedures as in Example 9 using -N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.61 (2H, m), 1.70-1.78 (2H, m), 2.25 (3H, s), 2.31 (3H, s), 2.46 (2H, t , J = 7.5Hz), 2.55-2.59 (2H, m), 2.76-2.80 (2H, m), 2.94 (2H, t, J = 7.3Hz), 3.23 (2H, t, J = 8.3Hz), 3.81 (3H, s), 4.11 (2H, t, J = 8.3Hz), 6.82-6.87 (2H, m), 7.12-7.19 (2H, m), 7.81-7.84 (2H, m), 8.23 (1H, d , J = 8.3Hz).
IR (free base; neat) νcm ^-1 : 1673, 1603, 1493, 1440, 1394, 1329, 1244.

参考例１１で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-クロロペンタン-1-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.54-1.61(2H, m), 1.70-1.77(2H, m), 2.24(3H, s), 2.33(3H, s), 2.47(2H, t, J = 6.3Hz), 2.61(2H, t, J = 7Hz), 2.88-2.95(4H, m), 3.22(2H, t, J = 7.5Hz), 4.10(2H, t, J = 7.5Hz), 7.11-7.33(4H, m), 7.79-7.83(2H, m), 8.22(1H, d, J = 8.5Hz).
IR (フリー塩基; neat)νcm^-1: 1673, 1604, 1489, 1440, 1391, 1330, 1256. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] -1-pentanone hydrochloride

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-chloropentan-1-one and N- [2- (2-chlorophenyl) ethyl]-obtained in Reference Example 11 The title compound was obtained as a yellow amorphous powder by performing the same operation as in Example 9 using N-methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.61 (2H, m), 1.70-1.77 (2H, m), 2.24 (3H, s), 2.33 (3H, s), 2.47 (2H, t , J = 6.3Hz), 2.61 (2H, t, J = 7Hz), 2.88-2.95 (4H, m), 3.22 (2H, t, J = 7.5Hz), 4.10 (2H, t, J = 7.5Hz) , 7.11-7.33 (4H, m), 7.79-7.83 (2H, m), 8.22 (1H, d, J = 8.5Hz).
IR (free base; neat) νcm ^-1 : 1673, 1604, 1489, 1440, 1391, 1330, 1256.

参考例１２で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-6-ブロモ-1-ヘキサノン(388mg) および2-(2−メトキシフェニル)エチルアミン(378mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(140mg) を融点186-187℃の無色結晶として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.35-1.43(2H, m), 1.49-1.56(2H, m), 1.64(1H, br.s), 1.69-1.76(2H, m), 2.24(3H, s), 2.68(2H, t, J = 7Hz), 2.83(4H, br.s), 2.91(2H, t, J = 7Hz), 3.22(2H, t, J = 8.3Hz), 3.81(3H, s), 4.11(2H, t, J = 8.3Hz), 6.83-6.88(2H, m), 7.13-7.20(2H, m), 7.79-7.82(2H, m), 8.23(1H, d, J = 8.3Hz).
IR (フリー塩基; neat)νcm^-1: 1673, 1602, 1493, 1440, 1394, 1329, 1243. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -6-[[2- (2-methoxyphenyl) ethyl] amino] -1-hexanone hydrochloride

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -6-bromo-1-hexanone (388 mg) and 2- (2-methoxyphenyl) ethylamine (378 mg) obtained in Reference Example 12 ) To give the title compound (140 mg) as colorless crystals with a melting point of 186-187 ° C. by a similar operation as in Example 9.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.35-1.43 (2H, m), 1.49-1.56 (2H, m), 1.64 (1H, br.s), 1.69-1.76 (2H, m), 2.24 (3H, s), 2.68 (2H, t, J = 7Hz), 2.83 (4H, br.s), 2.91 (2H, t, J = 7Hz), 3.22 (2H, t, J = 8.3Hz), 3.81 (3H, s), 4.11 (2H, t, J = 8.3Hz), 6.83-6.88 (2H, m), 7.13-7.20 (2H, m), 7.79-7.82 (2H, m), 8.23 (1H, d , J = 8.3Hz).
IR (free base; neat) νcm ^-1 : 1673, 1602, 1493, 1440, 1394, 1329, 1243.

参考例１２で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-6-ブロモ-1-ヘキサノン(270mg) および2-(2−クロロフェニル)エチルアミン(311mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(128mg) を融点182-183℃の無色結晶として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.38-1.44(2H, m), 1.47(1H, br.s), 1.50-1.57(2H, m), 1.70-1.77(2H, m), 2.24(3H, s), 2.66(2H, t, J = 7.5Hz), 2.85-2.94(6H, m), 3.22(2H, t, J = 8Hz), 4.10(2H, t, J = 8Hz), 7.14-7.35(4H, m), 7.79-7.82(2H, m), 8.22(1H, d, J = 8.5Hz).
IR (フリー塩基; neat)νcm^-1: 1673, 1604, 1489, 1441, 1395, 1330, 1262. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -6-[[2- (2-chlorophenyl) ethyl] amino] -1-hexanone hydrochloride

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -6-bromo-1-hexanone (270 mg) and 2- (2-chlorophenyl) ethylamine (311 mg) obtained in Reference Example 12 By using the same procedure as in Example 9, the title compound (128 mg) was obtained as colorless crystals having a melting point of 182-183 ° C.
¹ H NMR (free _{base; 400MHz, CDCl 3) δ 1.38-1.44} (2H, m), 1.47 (1H, br.s), 1.50-1.57 (2H, m), 1.70-1.77 (2H, m), 2.24 (3H, s), 2.66 (2H, t, J = 7.5Hz), 2.85-2.94 (6H, m), 3.22 (2H, t, J = 8Hz), 4.10 (2H, t, J = 8Hz), 7.14 -7.35 (4H, m), 7.79-7.82 (2H, m), 8.22 (1H, d, J = 8.5Hz).
IR (free base; neat) νcm ^-1 : 1673, 1604, 1489, 1441, 1395, 1330, 1262.

参考例１２で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-6-ブロモ-1-ヘキサノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を黄色非晶状粉末として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.36-1.42(2H, m), 1.51-1.58(2H, m), 1.70-1.78(2H, m), 2.24(3H, s), 2.31(3H, s), 2.42(2H, t, J = 7.5Hz), 2.55-2.59(2H, m), 2.76-2.80(2H, m), 2.92(2H, t, J = 7.5Hz), 3.21(2H, t, J = 8.3Hz), 3.81(3H, s), 4.09(2H, t, J = 8.3Hz), 6.82-6.89(2H, m), 7.12-7.19(2H, m), 7.79-7.83(2H, m), 8.23(1H, d, J = 8.3Hz).
IR (フリー塩基; neat)νcm^-1: 1674, 1603, 1493, 1440, 1394, 1329, 1244. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -6-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] -1-hexanone hydrochloride

1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -6-bromo-1-hexanone and N- [2- (2-methoxyphenyl) ethyl]-obtained in Reference Example 12 The title compound was obtained as a yellow amorphous powder by performing the same operation as in Example 9 using N-methylamine.
¹ H NMR (free _{base; 400MHz, CDCl 3) δ 1.36-1.42} (2H, m), 1.51-1.58 (2H, m), 1.70-1.78 (2H, m), 2.24 (3H, s), 2.31 (3H , s), 2.42 (2H, t, J = 7.5Hz), 2.55-2.59 (2H, m), 2.76-2.80 (2H, m), 2.92 (2H, t, J = 7.5Hz), 3.21 (2H, t, J = 8.3Hz), 3.81 (3H, s), 4.09 (2H, t, J = 8.3Hz), 6.82-6.89 (2H, m), 7.12-7.19 (2H, m), 7.79-7.83 (2H , m), 8.23 (1H, d, J = 8.3Hz).
IR (free base; neat) νcm ^-1 : 1674, 1603, 1493, 1440, 1394, 1329, 1244.

参考例１２で得た1-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-6-ブロモ-1-ヘキサノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点177-178℃の無色結晶として得た。
¹H NMR(フリー塩基; 400MHz, CDCl₃) δ 1.35-1.42(2H, m), 1.50-1.58(2H, m), 1.70-1.78(2H, m), 2.25(3H, s), 2.33(3H, s), 2.43(2H, t, J = 7Hz), 2.58-2.62(2H, m), 2.88-2.95(4H, m), 3.23(2H, t, J = 8Hz), 4.10(2H, t, J = 8Hz), 7.11-7.33(4H, m), 7.80-7.83(2H, m), 8.22(1H, d, J = 8.5Hz).
IR (フリー塩基; neat)νcm^-1: 1674, 1604, 1489, 1441, 1394, 1329, 1246. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -6-[[2- (2-chlorophenyl) ethyl] (methyl) amino] -1-hexanone hydrochloride

1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -6-bromo-1-hexanone and N- [2- (2-chlorophenyl) ethyl] -N obtained in Reference Example 12 -The title compound was obtained as colorless crystals having a melting point of 177-178 ° C by the same procedure as in Example 9 using methylamine.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.35-1.42 (2H, m), 1.50-1.58 (2H, m), 1.70-1.78 (2H, m), 2.25 (3H, s), 2.33 (3H , s), 2.43 (2H, t, J = 7Hz), 2.58-2.62 (2H, m), 2.88-2.95 (4H, m), 3.23 (2H, t, J = 8Hz), 4.10 (2H, t, J = 8Hz), 7.11-7.33 (4H, m), 7.80-7.83 (2H, m), 8.22 (1H, d, J = 8.5Hz).
IR (free base; neat) νcm ^-1 : 1674, 1604, 1489, 1441, 1394, 1329, 1246.

参考例４１で得た5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル(2-フェニルエチル)カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.68 (4H, br.), 2.96-3.01（6H, m）, 3.10(2H, br.s), 4.69(2H, s), 7.05(1H, d, J = 8.4 Hz), 7.26-7.37(5H, m), 7.53(1H, d, J = 1.8 Hz), 7.63(1H, dd, J = 8.4, 1.5 Hz), 9.13(2H, br), 10.95(1H, s).
[M+H]⁺(ESI+)＝353, HPLC 純度 94%(220nm) 6- [5-[(2-Phenylethyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

Using tert-butyl 5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl (2-phenylethyl) carbamate obtained in Reference Example 41 By performing the same operation as in Example 1, the title compound was obtained as a colorless amorphous powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.68 (4H, br.), 2.96-3.01 (6H, m), 3.10 (2H, br.s), 4.69 (2H, s), 7.05 (1H, d , J = 8.4 Hz), 7.26-7.37 (5H, m), 7.53 (1H, d, J = 1.8 Hz), 7.63 (1H, dd, J = 8.4, 1.5 Hz), 9.13 (2H, br), 10.95 (1H, s).
[M + H] ⁺ (ESI +) = 353, HPLC purity 94% (220nm)

参考例２３３で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]メタンスルホンアミドおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.52-1.81 (4H, m), 2.33 (3H, s), 2.47 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.64-2.98 (6H, m), 3.01 (3H, s), 3.35 (2H, dd, J = 16.4, 7.2 Hz), 4.30 (1H, m), 5.08 (1H, br), 7.07-7.34 (5H, m), 7.78 (2H, m). N- (5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) methanesulfonamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide and N- [2- (2-chlorophenyl) ethyl]-obtained in Reference Example 233 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9 using N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.52-1.81 (4H, m), 2.33 (3H, s), 2.47 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.64- 2.98 (6H, m), 3.01 (3H, s), 3.35 (2H, dd, J = 16.4, 7.2 Hz), 4.30 (1H, m), 5.08 (1H, br), 7.07-7.34 (5H, m) , 7.78 (2H, m).

参考例４２で得た2-(2-エトキシフェニル)エチル[5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.67(4H, br.), 2.95-3.02(8H, m), 3.52(2H, br.s), 3.80(3H, s), 4.69(2H, s), 6.89-6.99（1H, m）, 6.99-7.04(2H, m), 7.20-7.28(2H, m), 7.54（1H, d, J = 1.8 Hz）, 7.63(1H, dd, J = 8.4, 1.5Hz), 9.11(2H, br.), 10.96(1H,s).
MS m/z: 397 [M+H]⁺ 6- (5-[[2- (2-Ethoxyphenyl) ethyl] amino] pentanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (2-Ethoxyphenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid obtained in Reference Example 42 The same operation as in Example 1 was carried out using tert-butyl to obtain the title compound as a colorless amorphous powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.67 (4H, br.), 2.95-3.02 (8H, m), 3.52 (2H, br.s), 3.80 (3H, s), 4.69 (2H, s ), 6.89-6.99 (1H, m), 6.99-7.04 (2H, m), 7.20-7.28 (2H, m), 7.54 (1H, d, J = 1.8 Hz), 7.63 (1H, dd, J = 8.4 , 1.5Hz), 9.11 (2H, br.), 10.96 (1H, s).
MS m / z: 397 [M + H] ⁺

参考例４３で得た2-(2-フルオロフェニル)エチル[5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.67(4H, m), 3.00-3.04(6H, m), 3.09(2H, m), 4.69(2H, s), 7.06(1H, d, J = 8.1Hz), 7.17-7.24(2H, m), 7.30-7.38(2H, m), 7.51（1H, d, J = 1.8 Hz）, 7.63(1H, dd, J = 8.4, 1.8Hz), 9.04(2H, br.), 10.93(1H, s).
MS m/z: 371 [M+H]⁺ 6- (5-[[2- (2-Fluorophenyl) ethyl] amino] pentanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (2-Fluorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid obtained in Reference Example 43 The same operation as in Example 1 was carried out using tert-butyl to obtain the title compound as a colorless amorphous powder.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.67 (4H, m), 3.00-3.04 (6H, m), 3.09 (2H, m), 4.69 (2H, s), 7.06 (1H, d, J = 8.1Hz), 7.17-7.24 (2H, m), 7.30-7.38 (2H, m), 7.51 (1H, d, J = 1.8 Hz), 7.63 (1H, dd, J = 8.4, 1.8Hz), 9.04 ( 2H, br.), 10.93 (1H, s).
MS m / z: 371 [M + H] ⁺

参考例４４で得た2-(2-クロロフェニル)エチル[5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.68(4H,m), 2.98-3.02(4H, m), 3.11(4H, br.), 4.69(2H, s), 7.04(1H, d, J = 8.1Hz), 7.31-7.49(4H, m), 7.52（1H, d, J = 1.5 Hz）, 7.63(1H, dd, J = 8.3, 1.4Hz), 9.13(2H, br.), 10.93(1H, s).
MS m/z: 387 [M+H]⁺ 6- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (2-Chlorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert obtained in Reference Example 44 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 1 using -butyl.
^{1 H NMR (300MHz, DMSO-} d 6) δ 1.68 (4H, m), 2.98-3.02 (4H, m), 3.11 (4H, br.), 4.69 (2H, s), 7.04 (1H, d, J = 8.1Hz), 7.31-7.49 (4H, m), 7.52 (1H, d, J = 1.5 Hz), 7.63 (1H, dd, J = 8.3, 1.4Hz), 9.13 (2H, br.), 10.93 ( 1H, s).
MS m / z: 387 [M + H] ⁺

参考例４５で得た2-(3-メトキシフェニル)エチル[5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.67(4H, br.), 2.92-3.02(6H, m), 3.13(2H, br.), 3.75(3H, s), 4.69(2H, s), 6.82-6.84(3H, m), 7.05(1H, d, J = 8.4 Hz), 7.23-7.28(1H, m), 7.52(1H, d, J = 2.1 Hz), 7.63(1H, dd, J = 8.3, 2.0Hz),
9.03(2H, br.), 10.93(1H, s).
MS m/z: 383 [M+H]⁺ 6- (5-[[2- (3-Methoxyphenyl) ethyl] amino] pentanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (3-Methoxyphenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid obtained in Reference Example 45 The same operation as in Example 1 was carried out using tert-butyl to obtain the title compound as a colorless amorphous powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.67 (4H, br.), 2.92-3.02 (6H, m), 3.13 (2H, br.), 3.75 (3H, s), 4.69 (2H, s) , 6.82-6.84 (3H, m), 7.05 (1H, d, J = 8.4 Hz), 7.23-7.28 (1H, m), 7.52 (1H, d, J = 2.1 Hz), 7.63 (1H, dd, J = 8.3, 2.0Hz),
9.03 (2H, br.), 10.93 (1H, s).
MS m / z: 383 [M + H] ⁺

参考例４６で得た2-(3-エトキシフェニル)エチル[5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.32(3H, t, J =6.9 Hz), 1.67(4H, br.), 2.91-3.02(6H, m), 3.11(2H, br.), 4.01(2H, q, J = 6.9Hz), 4.68(2H, s), 6.80-6.82(3H, m), 7.05(1H, d, J = 8.4Hz), 7.21-7.26(1H, m), 7.52（1H, d, J = 1.8 Hz）, 7.63(1H, dd, J = 8.3, 1.4Hz), 9.02(2H, br.), 10.93(1H, s).
MS m/z: 397 [M+H]⁺ 6- (5-[[2- (3-Ethoxyphenyl) ethyl] amino] pentanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (3-Ethoxyphenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid obtained in Reference Example 46 The same operation as in Example 1 was carried out using tert-butyl to obtain the title compound as a colorless amorphous powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.32 (3H, t, J = 6.9 Hz), 1.67 (4H, br.), 2.91-3.02 (6H, m), 3.11 (2H, br.), 4.01 (2H, q, J = 6.9Hz), 4.68 (2H, s), 6.80-6.82 (3H, m), 7.05 (1H, d, J = 8.4Hz), 7.21-7.26 (1H, m), 7.52 ( 1H, d, J = 1.8 Hz), 7.63 (1H, dd, J = 8.3, 1.4 Hz), 9.02 (2H, br.), 10.93 (1H, s).
MS m / z: 397 [M + H] ⁺

参考例５６で得た2-(3-フルオロフェニル)エチル[5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.67(4H, br.), 2.95-3.03(6H, m), 3.14(2H, br.), 4.69(2H, s), 7.06(1H, d, J = 8.4Hz), 7.09-7.17(3H, m), 7.34-7.42（1H,
m）, 7.52(1H, d, J = 1.8 Hz), 7.63(1H, dd, J = 8.3, 1.4Hz), 9.04(2H, br.), 10.93(1H, s).
MS m/z: 371 [M+H]⁺ 6- (5-[[2- (3-Fluorophenyl) ethyl] amino] pentanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (3-Fluorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid obtained in Reference Example 56 The same operation as in Example 1 was carried out using tert-butyl to obtain the title compound as a colorless amorphous powder.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.67 (4H, br.), 2.95-3.03 (6H, m), 3.14 (2H, br.), 4.69 (2H, s), 7.06 (1H, d, J = 8.4Hz), 7.09-7.17 (3H, m), 7.34-7.42 (1H,
m), 7.52 (1H, d, J = 1.8 Hz), 7.63 (1H, dd, J = 8.3, 1.4 Hz), 9.04 (2H, br.), 10.93 (1H, s).
MS m / z: 371 [M + H] ⁺

参考例５７で得た2-(3-クロロフェニル)エチル[5-オキソ-5-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.67(4H, br.), 2.95-3.02(6H, m), 3.13(2H, br.), 4.69(2H, s), 7.06(1H, d, J = 8.1Hz), 7.24-7.38(4H, m), 7.52(1H, d, J = 1.8 Hz), 7.63(1H, dd, J = 8.3, 1.1Hz), 9.06(2H, br.), 10.94(1H, s).
MS m/z: 387 [M+H]⁺ 6- (5-[[2- (3-Chlorophenyl) ethyl] amino] pentanoyl) -2H-1, 4-benzoxazin-3 (4H) -one hydrochloride

2- (3-Chlorophenyl) ethyl [5-oxo-5- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) pentyl] carbamic acid tert obtained in Reference Example 57 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 1 using -butyl.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.67 (4H, br.), 2.95-3.02 (6H, m), 3.13 (2H, br.), 4.69 (2H, s), 7.06 (1H, d, J = 8.1Hz), 7.24-7.38 (4H, m), 7.52 (1H, d, J = 1.8 Hz), 7.63 (1H, dd, J = 8.3, 1.1Hz), 9.06 (2H, br.), 10.94 (1H, s).
MS m / z: 387 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.68(4H, br.), 2.81(3H, s), 2.98-3.44(8H, m), 4.67(2H, s), 7.04(1H, d, J = 8.6Hz), 7.25-7.51(5H, m), 7.49(1H, d, J = 2.0Hz), 7.62(1H, dd, J = 8.6, 2.0Hz), 9.93(1H, br.s), 10.88(1H, s).
MS m/z: 381 [M+H]⁺ 6- [5- [Methyl (2-phenylethyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

Using 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N-methyl-N- (2-phenylethyl) amine obtained in Reference Example 7, The title compound was obtained as a colorless amorphous powder by the same operation as in Example 9.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.68 (4H, br.), 2.81 (3H, s), 2.98-3.44 (8H, m), 4.67 (2H, s), 7.04 (1H, d, J = 8.6Hz), 7.25-7.51 (5H, m), 7.49 (1H, d, J = 2.0Hz), 7.62 (1H, dd, J = 8.6, 2.0Hz), 9.93 (1H, br.s), 10.88 (1H, s).
MS m / z: 381 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.68(4H, br.), 2.82(3H, d, J = 3.4Hz), 2.94-3.23(8H, br.), 3.82(3H, s), 4.67(2H, s), 6.92(1H, t, J = 4.9Hz), 7.01(1H, d, J = 8.4Hz), 7.04(1H, d, J = 8.2Hz), 7.21-7.29(2H, m), 7.50(1H, d, J = 1.4Hz), 7.62(1H, dd, J = 5.7, 1.3Hz), 9.97(1H, br.s), 10.89(1H, s).
MS m/z: 397 [M+H]⁺ 6- [5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (5-Chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 7 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.68 (4H, br.), 2.82 (3H, d, J = 3.4Hz), 2.94-3.23 (8H, br.), 3.82 (3H, s), 4.67 (2H, s), 6.92 (1H, t, J = 4.9Hz), 7.01 (1H, d, J = 8.4Hz), 7.04 (1H, d, J = 8.2Hz), 7.21-7.29 (2H, m) , 7.50 (1H, d, J = 1.4Hz), 7.62 (1H, dd, J = 5.7, 1.3Hz), 9.97 (1H, br.s), 10.89 (1H, s).
MS m / z: 397 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-フルオロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.68(4H, br.), 2.82(3H, d, J = 4.8Hz), 2.98-3.34(8H, br.), 4.67(2H, s), 7.04(1H, d, J = 8.0Hz), 7.15-7.24(2H, m), 7.28-7.40(2H, m), 7.51(1H, d, J = 1.8Hz), 7.62(1H, dd, J = 8.6, 2.2Hz), 10.26(1H, br.s), 10.89(1H, s).
MS m/z: 385 [M+H]⁺ 6- [5-[[2- (2-Fluorophenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (5-Chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-fluorophenyl) ethyl] -N-methylamine obtained in Reference Example 7 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.68 (4H, br.), 2.82 (3H, d, J = 4.8Hz), 2.98-3.34 (8H, br.), 4.67 (2H, s), 7.04 (1H, d, J = 8.0Hz), 7.15-7.24 (2H, m), 7.28-7.40 (2H, m), 7.51 (1H, d, J = 1.8Hz), 7.62 (1H, dd, J = 8.6 , 2.2Hz), 10.26 (1H, br.s), 10.89 (1H, s).
MS m / z: 385 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.69(4H, br.), 2.83(3H, s), 2.97(2H, t, J = 7Hz), 3.18(6H, m), 4.67(2H, s), 7.04(1H, d, J = 8.2Hz), 7.30-7.38(2H, m), 7.43-7.51(2H, m), 7.59(1H, d, J = 1.8Hz), 7.62(1H, dd, J = 8.4, 1.8Hz), 10.36(1H, br.s), 10.87(1H, s).
MS m/z: 401 [M+H]⁺ 6- [5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

The 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 7 were used. Using the same procedure as in Example 9, the title compound was obtained as a colorless amorphous powder.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.69 (4H, br.), 2.83 (3H, s), 2.97 (2H, t, J = 7Hz), 3.18 (6H, m), 4.67 (2H, s ), 7.04 (1H, d, J = 8.2Hz), 7.30-7.38 (2H, m), 7.43-7.51 (2H, m), 7.59 (1H, d, J = 1.8Hz), 7.62 (1H, dd, J = 8.4, 1.8Hz), 10.36 (1H, br.s), 10.87 (1H, s).
MS m / z: 401 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.68(4H, br.), 2.82(3H, d, J = 3.2Hz), 2.96-3.34(8H, br.), 3.76(3H, s), 4.67(2H, s), 6.81(1H, d, J = 1.6Hz), 6.86(2H, d, J = 5.6Hz), 7.04(1H, d, J = 5.8Hz), 7.25(1H, t, J = 5.2Hz), 7.50(1H, d, J = 1.6Hz), 7.61(1H, dd, J = 5.6, 1.4Hz), 9.68(1H, br.s), 10.89(1H, s).
MS m/z: 397 [M+H]⁺ 6- [5-[[2- (3-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (5-Chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-methoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 7 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.68 (4H, br.), 2.82 (3H, d, J = 3.2Hz), 2.96-3.34 (8H, br.), 3.76 (3H, s), 4.67 (2H, s), 6.81 (1H, d, J = 1.6Hz), 6.86 (2H, d, J = 5.6Hz), 7.04 (1H, d, J = 5.8Hz), 7.25 (1H, t, J = 5.2Hz), 7.50 (1H, d, J = 1.6Hz), 7.61 (1H, dd, J = 5.6, 1.4Hz), 9.68 (1H, br.s), 10.89 (1H, s).
MS m / z: 397 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.68(4H, br.), 2.82(3H, d, J= 4.5Hz), 2.98-3.36(8H, br.), 4.67(2H, s), 7.02-7.19(4H, m), 7.34-7.42(1H, m), 7.50(1H, d, J = 2.1Hz), 7.63(1H, dd, J = 8.7, 2.1Hz), 9.69(1H, br.s), 10.88(1H, s).
MS m/z: 385 [M+H]⁺ 6- [5-[[2- (3-Fluorophenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (5-Chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-fluorophenyl) ethyl] -N-methylamine obtained in Reference Example 7 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.68 (4H, br.), 2.82 (3H, d, J = 4.5 Hz), 2.98-3.36 (8H, br.), 4.67 (2H, s), 7.02 -7.19 (4H, m), 7.34-7.42 (1H, m), 7.50 (1H, d, J = 2.1Hz), 7.63 (1H, dd, J = 8.7, 2.1Hz), 9.69 (1H, br.s ), 10.88 (1H, s).
MS m / z: 385 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.68(4H, br.), 2.81(3H, d, J = 4.8Hz), 3.03-3.63(8H, br.), 4.67(2H, s), 7.04（1H, d, J = 8.4Hz）, 7.25-7.42(4H, m), 7.51(1H, d, J = 1.8Hz), 7.62(1H, dd, J = 8.4, 1.8Hz), 10.06(1H, br.s), 10.90(1H, s).
MS m/z: 401 [M+H]⁺ 6- [5-[[2- (3-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

The 6- (5-chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 7 were used. Using the same procedure as in Example 9, the title compound was obtained as a colorless amorphous powder.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.68 (4H, br.), 2.81 (3H, d, J = 4.8Hz), 3.03-3.63 (8H, br.), 4.67 (2H, s), 7.04 (1H, d, J = 8.4Hz), 7.25-7.42 (4H, m), 7.51 (1H, d, J = 1.8Hz), 7.62 (1H, dd, J = 8.4, 1.8Hz), 10.06 (1H, br.s), 10.90 (1H, s).
MS m / z: 401 [M + H] ⁺

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.31-1.41(2H, m), 1.61-1.79(4H, m), 2.79(3H, d, J = 4.8Hz), 2.92-3.42(8H, br.), 3.81(3H, s), 4.67(2H, s), 6.87-7.05(3H, m), 7.20-7.30(2H, m), 7.50(1H, d, J = 1.8Hz), 7.61(1H, dd, J = 8.2, 2.0Hz), 10.13(1H, br.s), 10.85(1H, s).
MS m/z: 411 [M+H]⁺ 6- [6-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 8 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.31-1.41 (2H, m), 1.61-1.79 (4H, m), 2.79 (3H, d, J = 4.8Hz), 2.92-3.42 (8H, br. ), 3.81 (3H, s), 4.67 (2H, s), 6.87-7.05 (3H, m), 7.20-7.30 (2H, m), 7.50 (1H, d, J = 1.8Hz), 7.61 (1H, dd, J = 8.2, 2.0Hz), 10.13 (1H, br.s), 10.85 (1H, s).
MS m / z: 411 [M + H] ⁺

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-フルオロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.32-1.42(2H, m), 1.61-1.78(4H, m), 2.81(3H, s), 2.92-3.30(8H, br.), 4.67(2H, s), 7.03(1H, d, J = 8.4Hz), 7.05-7.24(2H, m), 7.29-7.43(2H, m), 7.51(1H, d, J = 1.8Hz), 7.61(1H, dd, J = 8.4, 1.8Hz), 10.60(1H, br.s), 10.90(1H, s).
MS m/z: 399 [M+H]⁺ 6- [6-[[2- (2-Fluorophenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-fluorophenyl) ethyl] -N-methylamine obtained in Reference Example 8 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.32-1.42 (2H, m), 1.61-1.78 (4H, m), 2.81 (3H, s), 2.92-3.30 (8H, br.), 4.67 (2H , s), 7.03 (1H, d, J = 8.4Hz), 7.05-7.24 (2H, m), 7.29-7.43 (2H, m), 7.51 (1H, d, J = 1.8Hz), 7.61 (1H, dd, J = 8.4, 1.8Hz), 10.60 (1H, br.s), 10.90 (1H, s).
MS m / z: 399 [M + H] ⁺

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.33-1.43(2H, m), 1.61-1.78(4H, m), 2.85(3H, d, J = 4.8Hz), 2.96(2H, t, J = 7Hz), 3.12-3.21(6H, m), 4.66(2H, s), 7.03(1H, d, J = 8.4Hz), 7.27-7.37(2H, m), 7.41-7.48(2H, m), 7.50(1H, d, J = 2.0Hz), 7.60(1H, dd, J = 8.2, 2.0Hz), 10.24(1H, br.s), 10.87(1H, s).
MS m/z: 415 [M+H]⁺ 6- [6-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 8 were used. Using the same procedure as in Example 9, the title compound was obtained as a colorless amorphous powder.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.33-1.43 (2H, m), 1.61-1.78 (4H, m), 2.85 (3H, d, J = 4.8Hz), 2.96 (2H, t, J = 7Hz), 3.12-3.21 (6H, m), 4.66 (2H, s), 7.03 (1H, d, J = 8.4Hz), 7.27-7.37 (2H, m), 7.41-7.48 (2H, m), 7.50 (1H, d, J = 2.0Hz), 7.60 (1H, dd, J = 8.2, 2.0Hz), 10.24 (1H, br.s), 10.87 (1H, s).
MS m / z: 415 [M + H] ⁺

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.34(2H, br.), 1.61-1.78(4H, m), 2.79(3H, d, J = 3.8Hz), 2.96-3.26(8H, m), 3.75(3H, s), 4.67(2H, s), 6.84(3H, t, J = 6.9Hz), 7.03(1H, d, J = 8.4Hz), 7.25(1H, t, J = 8.0Hz), 7.52(1H, s), 7.61(1H, d, J = 7.4Hz), 10.5(1H, br.s), 10.91(1H, s).
MS m/z: 411 [M+H]⁺ 6- [6-[[2- (3-Methoxyphenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-methoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 8 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.34 (2H, br.), 1.61-1.78 (4H, m), 2.79 (3H, d, J = 3.8Hz), 2.96-3.26 (8H, m), 3.75 (3H, s), 4.67 (2H, s), 6.84 (3H, t, J = 6.9Hz), 7.03 (1H, d, J = 8.4Hz), 7.25 (1H, t, J = 8.0Hz), 7.52 (1H, s), 7.61 (1H, d, J = 7.4Hz), 10.5 (1H, br.s), 10.91 (1H, s).
MS m / z: 411 [M + H] ⁺

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(300MHz, CD₃OD) δ 1.44-1.52(2H, br.), 1.73-1.86(4H, m), 2.94(3H, s), 3.00-3.19(4H, m), 3.23-3.49（4H, m）, 4.67(2H, s), 6.98-7.15(4H, m), 7.33-7.40(1H, m), 7.54(1H, d, J = 2.1Hz), 7.67(1H, dd, J = 8.4Hz, 2.2Hz).
MS m/z: 399 [M+H]⁺ 6- [6-[[2- (3-Fluorophenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-fluorophenyl) ethyl] -N-methylamine obtained in Reference Example 8 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (300 MHz, CD ₃ OD) δ 1.44-1.52 (2H, br.), 1.73-1.86 (4H, m), 2.94 (3H, s), 3.00-3.19 (4H, m), 3.23-3.49 ( 4H, m), 4.67 (2H, s), 6.98-7.15 (4H, m), 7.33-7.40 (1H, m), 7.54 (1H, d, J = 2.1Hz), 7.67 (1H, dd, J = (8.4Hz, 2.2Hz).
MS m / z: 399 [M + H] ⁺

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(200MHz, DMSO-d₆) δ 1.33-1.40(2H, br.), 1.62-1.76(4H, m), 2.80(3H, d, J = 4.8Hz), 2.93-3.63(8H, m), 4.67(2H, s), 7.03(1H, d, J = 8.1Hz), 7.26-7.30(4H, m), 7.51(1H, d, J = 1.8Hz), 7.61(1H, d, J = 8.4Hz, 2.1Hz), 10.5(1H, br.s), 10.9(1H, s).
MS m/z: 415 [M+H]⁺ 6- [6-[[2- (3-Chlorophenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 8 were used. Using the same procedure as in Example 9, the title compound was obtained as a colorless amorphous powder.
¹ H NMR (200 MHz, DMSO-d ₆ ) δ 1.33-1.40 (2H, br.), 1.62-1.76 (4H, m), 2.80 (3H, d, J = 4.8 Hz), 2.93-3.63 (8H, m ), 4.67 (2H, s), 7.03 (1H, d, J = 8.1Hz), 7.26-7.30 (4H, m), 7.51 (1H, d, J = 1.8Hz), 7.61 (1H, d, J = 8.4Hz, 2.1Hz), 10.5 (1H, br.s), 10.9 (1H, s).
MS m / z: 415 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-エトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.41(3H, t, J = 6.9Hz), 1.56-1.63(2H, m), 1.70-1.78(2H, m), 2.33(3H, s), 2.47(2H, t, J = 7.5 ), 2.57-2.62(2H, m), 2.77-2.84(2H, m), 2.93(2H, t, J = 7.3H), 3.99-4.06(2H, m), 4.68(2H, s), 5.60(1H, br.s), 6.80-6.89(2H, m), 7.00(1H, d, J = 8.4Hz), 7.10-7.26(2H, m), 7.51(1H, d, J = 2.4Hz), 7.61(1H, dd, J = 8.4, 2.1Hz).
MS m/z: 411 [M+H]⁺ 6- [5-[[2- (2-Ethoxyphenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (5-Chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-ethoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 7 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.41 (3H, t, J = 6.9 Hz), 1.56-1.63 (2H, m), 1.70-1.78 (2H, m), 2.33 (3H, s), 2.47 (2H, t, J = 7.5), 2.57-2.62 (2H, m), 2.77-2.84 (2H, m), 2.93 (2H, t, J = 7.3H), 3.99-4.06 (2H, m), 4.68 (2H, s), 5.60 (1H, br.s), 6.80-6.89 (2H, m), 7.00 (1H, d, J = 8.4Hz), 7.10-7.26 (2H, m), 7.51 (1H, d, J = 2.4Hz), 7.61 (1H, dd, J = 8.4, 2.1Hz).
MS m / z: 411 [M + H] ⁺

参考例７で得た6-(5-クロロペンタノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-エトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.40(3H, t, J = 6.9Hz), 1.53-1.61(2H, m), 1.69-1.76(2H, s), 2.30(3H, s), 2.45(2H, t, J = 7.4Hz), 2.57-2.63(2H, m), 2.69-2.76(2H, m), 2.91(2H, t, J = 7.2H), 4.00(2H,ｔ, J = 6.9Hz), 4.67(2H, s), 5.60(1H, br.s), 6.69-6.78(3H, m), 6.99(1H, d, J = 8.1Hz), 7.16(1H, ｔ, J = 8.0Hz), 7.52(1H, d, J = 1.8Hz), 7.58(1H, dd, J = 8.4, 2.1Hz).
MS m/z: 411 [M+H]⁺ 6- [5-[[2- (3-Ethoxyphenyl) ethyl] (methyl) amino] pentanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (5-Chloropentanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-ethoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 7 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.40 (3H, t, J = 6.9 Hz), 1.53-1.61 (2H, m), 1.69-1.76 (2H, s), 2.30 (3H, s), 2.45 (2H, t, J = 7.4Hz), 2.57-2.63 (2H, m), 2.69-2.76 (2H, m), 2.91 (2H, t, J = 7.2H), 4.00 (2H, t, J = 6.9Hz), 4.67 (2H, s), 5.60 (1H, br.s), 6.69-6.78 (3H, m), 6.99 (1H, d, J = 8.1Hz), 7.16 (1H, t, J = 8.0 Hz), 7.52 (1H, d, J = 1.8Hz), 7.58 (1H, dd, J = 8.4, 2.1Hz).
MS m / z: 411 [M + H] ⁺

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(2-エトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.37-1.44(5H, m), 1.53-1.60(2H, m), 1.71-1.78(2H, s), 2.34(3H, s), 2.45(2H, t, J = 7.4Hz), 2.55-2.64(2H, m), 2.76-2.93(4H, m), 3.96-4.06(2H, m), 4.67(2H, s), 5.32（1H, br.s）, 6.78-6.89(2H, m), 6.99(1H, d, J = 8.0Hz), 7.12(2H, d, J = 7.2Hz), 7.54(1H, d, J = 1.8Hz), 7.59(1H, dd, J = 8.2, 2.0Hz).
MS m/z: 425 [M+H]⁺ 6- [6-[[2- (2-Ethoxyphenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (2-ethoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 8 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.37-1.44 (5H, m), 1.53-1.60 (2H, m), 1.71-1.78 (2H, s), 2.34 (3H, s), 2.45 (2H , t, J = 7.4Hz), 2.55-2.64 (2H, m), 2.76-2.93 (4H, m), 3.96-4.06 (2H, m), 4.67 (2H, s), 5.32 (1H, br.s ), 6.78-6.89 (2H, m), 6.99 (1H, d, J = 8.0Hz), 7.12 (2H, d, J = 7.2Hz), 7.54 (1H, d, J = 1.8Hz), 7.59 (1H , dd, J = 8.2, 2.0Hz).
MS m / z: 425 [M + H] +

参考例８で得た6-(6-ブロモヘキサノイル)-2H-1,4-ベンゾオキサジン-3(4H)-オンおよびN-[2-(3-エトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.32-1.42(5H, m), 1.49-1.59(2H, m), 1.69-1.78(2H, s), 2.30(3H, s), 2.42(2H, t, J = 7.6Hz), 2.59-2.66(2H, m), 2.70-2.77(2H, m), 2.89(2H, t, J = 7.2Hz), 3.97-4.04(2H, m), 4.67(2H, s), 5.38（1H, br.s）, 6.69-6.78(3H, m), 6.98(1H, d, J = 8.1Hz), 7.17(1H, t, J = 7.7Hz), 7.55(1H, d, J = 1.8Hz), 7.58(1H, dd, J = 8.4, 2.1Hz).
MS m/z: 425 [M+H]⁺ 6- [6-[[2- (3-Ethoxyphenyl) ethyl] (methyl) amino] hexanoyl] -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

6- (6-Bromohexanoyl) -2H-1,4-benzoxazin-3 (4H) -one and N- [2- (3-ethoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 8 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.32-1.42 (5H, m), 1.49-1.59 (2H, m), 1.69-1.78 (2H, s), 2.30 (3H, s), 2.42 (2H , t, J = 7.6Hz), 2.59-2.66 (2H, m), 2.70-2.77 (2H, m), 2.89 (2H, t, J = 7.2Hz), 3.97-4.04 (2H, m), 4.67 ( 2H, s), 5.38 (1H, br.s), 6.69-6.78 (3H, m), 6.98 (1H, d, J = 8.1Hz), 7.17 (1H, t, J = 7.7Hz), 7.55 (1H , d, J = 1.8Hz), 7.58 (1H, dd, J = 8.4, 2.1Hz).
MS m / z: 425 [M + H] +

参考例９で得た5-(5-クロロペンタノイル)-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点240℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.65-1.75(4H, m), 2.80(3H, d, J = 4.8Hz), 3.00-3.08(6H, m), 3.23(2H, m), 7.03(1H, d, J = 8.1Hz), 7.26-7.36(5H, m), 7.67(1H, d, J = 8.4Hz),10.28(1H, s), 10.94(1H, s), 11.09(1H, s).
元素分析 C₂₁H₂₅N₃O₂・HCl・0.5H₂O として
計算値：C, 62.69; H, 6.91; N, 10.44.
実験値：C, 62.87; H, 6.63; N, 10.37.
MS m/z: 352 [M+H]⁺ 5- [5- [Methyl (2-phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Using 5- (5-chloropentanoyl) -1,3-dihydro-2H-benzimidazol-2-one and N-methyl-N- (2-phenylethyl) amine obtained in Reference Example 9, The title compound was obtained as colorless crystals having a melting point of 240 ° C. by carrying out the same operation as in 9.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.65-1.75 (4H, m), 2.80 (3H, d, J = 4.8 Hz), 3.00-3.08 (6H, m), 3.23 (2H, m), 7.03 (1H, d, J = 8.1Hz), 7.26-7.36 (5H, m), 7.67 (1H, d, J = 8.4Hz), 10.28 (1H, s), 10.94 (1H, s), 11.09 (1H, s).
Elemental analysis Calculated as C ₂₁ H ₂₅ N ₃ O ₂ · HCl · 0.5H ₂ O: C, 62.69; H, 6.91; N, 10.44.
Experimental value: C, 62.87; H, 6.63; N, 10.37.
MS m / z: 352 [M + H] ⁺

参考例９で得た5-(5-クロロペンタノイル)-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点169-180℃(封管中；分解)の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.65-1.75(4H, m), 2.80(3H, d, J = 4.8Hz), 2.92-3.30(8H, m), 3.81(3H, s), 6.89-6.95(1H, m), 7.00-7.04(2H, m), 7.21-7.30(2H, m), 7.50(1H, s), 7.69(1H, dd, J = 8.3, 1.7Hz), 10.09(1H, br.s), 10.95(1H, s), 11.09(1H, s).
MS m/z: 382 [M+H]⁺ 5- [5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (5-chloropentanoyl) -1,3-dihydro-2H-benzoimidazol-2-one and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 9 were Using the same procedure as in Example 9, the title compound was obtained as colorless crystals having a melting point of 169-180 ° C. (in a sealed tube; decomposition).
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.65-1.75 (4H, m), 2.80 (3H, d, J = 4.8 Hz), 2.92-3.30 (8H, m), 3.81 (3H, s), 6.89 -6.95 (1H, m), 7.00-7.04 (2H, m), 7.21-7.30 (2H, m), 7.50 (1H, s), 7.69 (1H, dd, J = 8.3, 1.7Hz), 10.09 (1H , br.s), 10.95 (1H, s), 11.09 (1H, s).
MS m / z: 382 [M + H] ⁺

参考例２３３で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]メタンスルホンアミドおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.52-1.81 (4H, m), 2.33 (3H, s), 2.47 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.78 (2H, m), 2.93 (4H, m), 3.00 (3H, s), 3.35 (2H, dd, J = 16.4, 7.0 Hz), 3.81 (3H, s), 4.32 (1H, m), 5.08 (1H, br), 6.81-6.90 (2H, m), 7.11-7.30 (3H, m), 7.78 (2H, m). N- (5- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) methanesulfonamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide and N- [2- (2-methoxyphenyl) ethyl] obtained in Reference Example 233 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9 using -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.52-1.81 (4H, m), 2.33 (3H, s), 2.47 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.78 ( 2H, m), 2.93 (4H, m), 3.00 (3H, s), 3.35 (2H, dd, J = 16.4, 7.0 Hz), 3.81 (3H, s), 4.32 (1H, m), 5.08 (1H , br), 6.81-6.90 (2H, m), 7.11-7.30 (3H, m), 7.78 (2H, m).

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点142-157℃(封管中；分解)の無色結晶として得た。
¹H NMR(フリー塩基; 300MHz, CDCl₃) δ 1.54-1.69(2H, m), 1.73-1.83(2H, m), 2.31(3H, s), 2.44-2.49(2H, m), 2.58-2.64(2H, m), 2.75-2.80(2H, m), 2.98-3.03(2H, m), 3.46(3H, s), 3.47(3H, s), 6.99(1H, d, J = 8.1Hz), 7.15-7.30(5H, m), 7.63(1H, d, J = 1.5Hz), 7.69(1H, dd, J = 8.3, 1.7Hz).
MS m/z: 380 [M+H]⁺ 1,3-Dimethyl-5- [5- [methyl (2-phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one and N-methyl-N- (2-phenylethyl) amine obtained in Reference Example 10 The title compound was obtained as colorless crystals having a melting point of 142-157 ° C. (in a sealed tube; decomposition) by conducting the same operation as in Example 9.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.54-1.69 (2H, m), 1.73-1.83 (2H, m), 2.31 (3H, s), 2.44-2.49 (2H, m), 2.58-2.64 (2H, m), 2.75-2.80 (2H, m), 2.98-3.03 (2H, m), 3.46 (3H, s), 3.47 (3H, s), 6.99 (1H, d, J = 8.1Hz), 7.15-7.30 (5H, m), 7.63 (1H, d, J = 1.5Hz), 7.69 (1H, dd, J = 8.3, 1.7Hz).
MS m / z: 380 [M + H] ⁺

参考例１０で得た5-(5-クロロペンタノイル)-1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点125-140℃(封管中；分解)の無色結晶として得た。
¹H NMR(フリー塩基; 200MHz, CDCl₃) δ 1.65-1.84(4H, m), 2.39(3H, s), 2.51-2.69(4H, m), 2.77-2.87(2H, m), 2.99-3.06(2H, m), 3.46(3H, s), 3.47(3H, s), 3.82(3H, s), 6.82-6.91(2H, m), 6.99(1H, d, J = 8.0Hz), 7.14-7.23(2H, m), 7.63(1H, d, J = 1.6Hz), 7.69(1H, dd, J = 8.4, 1.4Hz).
MS m/z: 410 [M+H]⁺ 5- [5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (5-Chloropentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one and N- [2- (2-methoxyphenyl) ethyl] obtained in Reference Example 10 The title compound was obtained as colorless crystals having a melting point of 125-140 ° C. (in a sealed tube; decomposition) by conducting the same operation as in Example 9 using -N-methylamine.
¹ H NMR (free _{base; 200MHz, CDCl 3) δ 1.65-1.84} (4H, m), 2.39 (3H, s), 2.51-2.69 (4H, m), 2.77-2.87 (2H, m), 2.99-3.06 (2H, m), 3.46 (3H, s), 3.47 (3H, s), 3.82 (3H, s), 6.82-6.91 (2H, m), 6.99 (1H, d, J = 8.0Hz), 7.14- 7.23 (2H, m), 7.63 (1H, d, J = 1.6Hz), 7.69 (1H, dd, J = 8.4, 1.4Hz).
MS m / z: 410 [M + H] ⁺

参考例２３３で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]メタンスルホンアミドおよび2-(2-クロロフェニル)エチルアミンを用い、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点156-158℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.52-1.81 (4H, m), 2.47 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.64-2.98 (6H, m), 3.01 (3H, s), 3.35 (2H, dd, J = 16.4, 7.2 Hz), 4.30 (1H, m), 5.08 (2H, br), 7.07-7.34 (5H, m), 7.78 (2H, m). N- [5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide hydrochloride

Using N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 233, Reference Example The title compound was obtained as colorless crystals having a melting point of 156-158 ° C. by sequentially carrying out the same operations as in 19 and Example 1.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.52-1.81 (4H, m), 2.47 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.64-2.98 (6H, m), 3.01 (3H, s), 3.35 (2H, dd, J = 16.4, 7.2 Hz), 4.30 (1H, m), 5.08 (2H, br), 7.07-7.34 (5H, m), 7.78 (2H, m) .

参考例９で得た5-(5-クロロペンタノイル)-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび２-フェニルエチルアミンを用いて、参考例１９および実施例１と同様の操作を行うことにより、表題化合物を融点259℃（封管中）の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.68(4H, m), 2.93-3.13(8H, m), 7.03(1H, d, J = 7.8Hz), 7.26-7.37(5H, m), 7.50(1H, s), 7.70(1H, d, J = 8.1Hz), 8.88(2H, br.s), 10.95(1H, s), 11.10(1H, s).
元素分析 C₂₀H₂₃N₃O₂・HClとして
計算値：C, 64.25; H, 6.47; N, 11.24.
実験値：C, 63.88; H, 6.50; N, 11.22
MS m/z: 338 [M+H]⁺ 5- [5-[(2-Phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

The same operations as in Reference Example 19 and Example 1 were carried out using 5- (5-chloropentanoyl) -1,3-dihydro-2H-benzimidazol-2-one and 2-phenylethylamine obtained in Reference Example 9. The title compound was obtained as colorless crystals having a melting point of 259 ° C. (in a sealed tube).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.68 (4H, m), 2.93-3.13 (8H, m), 7.03 (1H, d, J = 7.8Hz), 7.26-7.37 (5H, m), 7.50 (1H, s), 7.70 (1H, d, J = 8.1Hz), 8.88 (2H, br.s), 10.95 (1H, s), 11.10 (1H, s).
Elemental analysis Calculated as C ₂₀ H ₂₃ N ₃ O ₂ · HCl: C, 64.25; H, 6.47; N, 11.24.
Experimental value: C, 63.88; H, 6.50; N, 11.22
MS m / z: 338 [M + H] ⁺

参考例９で得た5-(5-クロロペンタノイル)-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび2-(2-メトキシフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を行うことにより、表題化合物を融点213℃（封管中）の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.67(4H, m), 2.94-3.04(8H, m), 3.80(3H, s), 6.89-6.94(1H, m), 6.99-7.04(2H, m), 7.17-7.29(2H, m), 7.50(1H, s), 7.69(1H, dd, J = 8.1, 1.5Hz), 8.86(2H, br.s), 10.95(1H, s), 11.10(1H, s).
元素分析 C₂₁H₂₅N₃O₃・HClとして
計算値：C, 62.45; H, 6.49; N, 10.40.
実験値：C, 62.20; H, 6.42; N, 10.38
MS m/z: 368 [M+H]⁺ 5- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Reference Example 19 and Example were obtained using 5- (5-chloropentanoyl) -1,3-dihydro-2H-benzimidazol-2-one and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 9. The title compound was obtained as colorless crystals having a melting point of 213 ° C. (in a sealed tube) by the same procedure as in 1.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.67 (4H, m), 2.94-3.04 (8H, m), 3.80 (3H, s), 6.89-6.94 (1H, m), 6.99-7.04 (2H, m), 7.17-7.29 (2H, m), 7.50 (1H, s), 7.69 (1H, dd, J = 8.1, 1.5Hz), 8.86 (2H, br.s), 10.95 (1H, s), 11.10 (1H, s).
Elemental analysis Calculated as C ₂₁ H ₂₅ N ₃ O ₃ · HCl: C, 62.45; H, 6.49; N, 10.40.
Experimental value: C, 62.20; H, 6.42; N, 10.38
MS m / z: 368 [M + H] ⁺

参考例９で得た5-(5-クロロペンタノイル)-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を行うことにより、表題化合物を融点233℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.68(4H, m), 2.99-3.11(8H, m), 7.03(1H, d, J = 8.1Hz), 7.31-7.48(5H, m), 7.69(1H, dd, J = 8.3, 1.6Hz), 8.99(2H, br.s), 10.95（1H, s）, 11.14(1H, s).
元素分析 C₂₀H₂₂N₃O₂Cl・HClとして
計算値：C, 58.83; H, 5.68; N, 10.29.
実験値：C, 58.51; H, 5.53; N, 10.26.
MS m/z: 372 [M+H]⁺ 5- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Reference Example 19 and Example 1 were obtained using 5- (5-chloropentanoyl) -1,3-dihydro-2H-benzimidazol-2-one and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 9. The title compound was obtained as colorless crystals having a melting point of 233 ° C. by carrying out the same operation as in.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.68 (4H, m), 2.99-3.11 (8H, m), 7.03 (1H, d, J = 8.1 Hz), 7.31-7.48 (5H, m), 7.69 (1H, dd, J = 8.3, 1.6Hz), 8.99 (2H, br.s), 10.95 (1H, s), 11.14 (1H, s).
Elemental analysis Calculated as C ₂₀ H ₂₂ N ₃ O ₂ Cl · HCl: C, 58.83; H, 5.68; N, 10.29.
Experimental value: C, 58.51; H, 5.53; N, 10.26.
MS m / z: 372 [M + H] ⁺

参考例５８で得た5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル(2-フェニルエチル)カルバミン酸tert-ブチルを用い、実施例１と同様の操作を行うことにより、表題化合物を融点187-189℃（封管中）の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.71(4H, m), 2.95-3.00(4H, m), 3.11（4H, m）, 3.36(3H, s), 3.38(3H, s), 7.26-7.38(6H, m), 7.74(1H, d, J = 1.2Hz), 7.82(1H, dd , J = 8.1, 1.5Hz), 9.03(2H, br.s).
元素分析 C₂₂H₂₇N₃O₂・HClとして
計算値：C, 65.74; H, 7.02; N, 10.45.
実験値：C, 65.38; H, 7.07; N, 10.55.
MS m/z: 366 [M+H]⁺ 1,3-Dimethyl-5- [5-[(2-phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Tert-Butyl 5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl (2-phenylethyl) carbamate obtained in Reference Example 58 The title compound was obtained as colorless crystals having a melting point of 187 ° -189 ° C. (in a sealed tube) by conducting the same operation as in Example 1.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.71 (4H, m), 2.95-3.00 (4H, m), 3.11 (4H, m), 3.36 (3H, s), 3.38 (3H, s), 7.26 -7.38 (6H, m), 7.74 (1H, d, J = 1.2Hz), 7.82 (1H, dd, J = 8.1, 1.5Hz), 9.03 (2H, br.s).
Elemental analysis Calculated as C ₂₂ H ₂₇ N ₃ O ₂ .HCl: C, 65.74; H, 7.02; N, 10.45.
Experimental value: C, 65.38; H, 7.07; N, 10.55.
MS m / z: 366 [M + H] ⁺

参考例５９で得た5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸tert-ブチルを用い、実施例１と同様の操作を行うことにより、表題化合物を融点178℃（封管中）の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.70(4H, m), 2.91-3.13(8H, m), 3.36(3H, s), 3.38(3H,s),3.80(3H, s), 6.89-6.94(1H, m), 6.99-7.02(1H, s), 7.17-7.20(1H, m), 7.23-7.29(2H, m), 7.74(1H, d, J = 1.2Hz), 7.82(1H, dd, J = 8.1, 1.5Hz), 8.92(2H, br.s).
元素分析 C₂₃H₂₉N₃O₃・HClとして
計算値：C, 63.95; H, 7.00; N, 9.73.
実験値：C, 63.72; H, 6.95; N, 9.75.
MS m/z: 396 [M+H]⁺ 5- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] obtained in Reference Example 59 The title compound was obtained as colorless crystals having a melting point of 178 ° C. (in a sealed tube) by carrying out the same operation as in Example 1 using tert-butyl carbamate.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.70 (4H, m), 2.91-3.13 (8H, m), 3.36 (3H, s), 3.38 (3H, s), 3.80 (3H, s), 6.89 -6.94 (1H, m), 6.99-7.02 (1H, s), 7.17-7.20 (1H, m), 7.23-7.29 (2H, m), 7.74 (1H, d, J = 1.2Hz), 7.82 (1H , dd, J = 8.1, 1.5Hz), 8.92 (2H, br.s).
Elemental analysis Calculated as C ₂₃ H ₂₉ N ₃ O ₃ .HCl: C, 63.95; H, 7.00; N, 9.73.
Experimental value: C, 63.72; H, 6.95; N, 9.75.
MS m / z: 396 [M + H] ⁺

参考例６０で得た2-(2-クロロフェニル)エチル[5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル]カルバミン酸tert-ブチルを用い、実施例１と同様の操作を行うことにより、表題化合物を融点168-169℃の無色結晶として得た。
¹H NMR(300MHz, DMSO-d₆) δ 1.71(4H, m), 3.01-3.11(8H, m), 3.36(3H, s), 3.38(3H,s), 7.26-7.49(5H, m), 7.74(1H, d, J = 1.2Hz), 7.82(1H, dd, J = 8.1, 1.5Hz), 9.03 (2H, br.s).
元素分析 C₂₂H₂₆N₃O₂Cl・HClとして
計算値：C, 60.55; H, 6.24; N, 9.62.
実験値：C, 60.33; H, 6.25; N, 9.62.
MS m/z: 400 [M+H]⁺ 5- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

2- (2-Chlorophenyl) ethyl [5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamine obtained in Reference Example 60 The title compound was obtained as colorless crystals with a melting point of 168-169 ° C. by carrying out the same operation as in Example 1 using tert-butyl acid.
¹ H NMR (300 MHz, DMSO-d ₆ ) δ 1.71 (4H, m), 3.01-3.11 (8H, m), 3.36 (3H, s), 3.38 (3H, s), 7.26-7.49 (5H, m) , 7.74 (1H, d, J = 1.2Hz), 7.82 (1H, dd, J = 8.1, 1.5Hz), 9.03 (2H, br.s).
Elemental analysis Calculated as C ₂₂ H ₂₆ N ₃ O ₂ Cl · HCl: C, 60.55; H, 6.24; N, 9.62.
Experimental values: C, 60.33; H, 6.25; N, 9.62.
MS m / z: 400 [M + H] ⁺

参考例６１で得た5-(1-ベンジル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸tert-ブチル(280mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(212mg) を融点88-89℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.61-1.65(4H, m), 2.85-3.00(10H, m), 3.47(2H,
t, J = 8.5Hz), 3.78(3H, s), 4.43(2H, s), 6.57(1H, d, J = 8.3Hz), 6.89(1H, t, J = 8.3Hz), 6.98(1H, d, J = 8.0Hz), 7.17(1H, d, J = 7.5Hz), 7.22-7.35(6H, m), 7.58(1H, br), 7.61(1H, s), 7.70(1H, d, J = 8.3Hz), 9.09(2H, s).
IR (KBr) νcm^-1: 3336, 2950, 2786, 1687, 1602, 1496, 1454, 1246, 753. 1- (1-Benzyl-2,3-dihydro-1H-indol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] amino] -1-pentanone dihydrochloride

Tert-Butyl 5- (1-benzyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate (280 mg) obtained in Reference Example 61 ) To give the title compound (212 mg) as colorless crystals with a melting point of 88-89 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.61-1.65 (4H, m), 2.85-3.00 (10H, m), 3.47 (2H,
t, J = 8.5Hz), 3.78 (3H, s), 4.43 (2H, s), 6.57 (1H, d, J = 8.3Hz), 6.89 (1H, t, J = 8.3Hz), 6.98 (1H, d, J = 8.0Hz), 7.17 (1H, d, J = 7.5Hz), 7.22-7.35 (6H, m), 7.58 (1H, br), 7.61 (1H, s), 7.70 (1H, d, J = 8.3Hz), 9.09 (2H, s).
IR (KBr) νcm ^-1 : 3336, 2950, 2786, 1687, 1602, 1496, 1454, 1246, 753.

参考例６２で得た5-(1-ベンゾイル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を融点151-152℃の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.61-1.71(4H, m), 2.98-3.03(8H, m), 3.18(2H, t, J = 8.0Hz), 3.79(3H, s) 4.05(2H, t, J = 8.3Hz), 6.89(1H, t, J = 7.5Hz), 6.98(1H, d, J = 7.5Hz), 7.17(1H, d, J = 7.5Hz), 7.24(1H, t, J = 7.5Hz), 7.47-7.60(6H, m), 7.85(1H, d, J = 6.6Hz), 7.87(1H, s), 9.19(2H, s).
IR (KBr) νcm^-1: 3336, 2948, 2781, 1680, 1644, 1602, 1495, 1440, 1386, 1334, 1254, 762. 1- (1-Benzoyl-2,3-dihydro-1H-indol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] amino] -1-pentanone hydrochloride

Using tert-butyl 5- (1-benzoyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 62 The title compound was obtained as colorless crystals having a melting point of 151-152 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.61-1.71 (4H, m), 2.98-3.03 (8H, m), 3.18 (2H, t, J = 8.0Hz), 3.79 (3H, s) 4.05 ( 2H, t, J = 8.3Hz), 6.89 (1H, t, J = 7.5Hz), 6.98 (1H, d, J = 7.5Hz), 7.17 (1H, d, J = 7.5Hz), 7.24 (1H, t, J = 7.5Hz), 7.47-7.60 (6H, m), 7.85 (1H, d, J = 6.6Hz), 7.87 (1H, s), 9.19 (2H, s).
IR (KBr) νcm ^-1 : 3336, 2948, 2781, 1680, 1644, 1602, 1495, 1440, 1386, 1334, 1254, 762.

参考例６３で得た5-[1-(アニリノカルボニル)-2,3-ジヒドロ-1H-インドール-5-イル]-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を融点205-206℃（分解）の無色結晶として得た。
¹H NMR(400MHz, DMSO-d₆) δ 1.63-1.68(4H, m), 2.93-3.03(8H, m), 3.21(2H, t, J = 8.5Hz), 3.79(3H, s), 4.23(2H, t, J = 8.3Hz), 6.89(1H, t, J = 7.5Hz), 6.98(1H, d, J = 8.3Hz), 7.02(1H, t, J = 7.5Hz), 7.17(1H, d, J = 7.5Hz), 7.24(1H, t, J = 7.5Hz), 7.29(2H, t, J = 6.6Hz), 7.59(2H, d, J = 8.5Hz), 7.79(1H, s), 7.82(1H, d, J = 8.5Hz), 7.93(1H, d, J = 8.5Hz), 8.78(1H, s), 9.10(2H,s).
IR (KBr) νcm^-1: 3400, 2936, 2771, 1680, 1597, 1539, 1491, 1445, 1340, 1246, 752. 5- (5-[[2- (2-Methoxyphenyl) ethyl] amino] pentanoyl) -N-phenyl-1-indolinecarboxamide hydrochloride

5- [1- (anilinocarbonyl) -2,3-dihydro-1H-indol-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamic acid tert obtained in Reference Example 63 The title compound was obtained as colorless crystals having a melting point of 205-206 ° C. (decomposition) by conducting the same operation as in Example 1 using -butyl.
¹ H NMR (400 MHz, DMSO-d ₆ ) δ 1.63-1.68 (4H, m), 2.93-3.03 (8H, m), 3.21 (2H, t, J = 8.5 Hz), 3.79 (3H, s), 4.23 (2H, t, J = 8.3Hz), 6.89 (1H, t, J = 7.5Hz), 6.98 (1H, d, J = 8.3Hz), 7.02 (1H, t, J = 7.5Hz), 7.17 (1H , d, J = 7.5Hz), 7.24 (1H, t, J = 7.5Hz), 7.29 (2H, t, J = 6.6Hz), 7.59 (2H, d, J = 8.5Hz), 7.79 (1H, s ), 7.82 (1H, d, J = 8.5Hz), 7.93 (1H, d, J = 8.5Hz), 8.78 (1H, s), 9.10 (2H, s).
IR (KBr) νcm ^-1 : 3400, 2936, 2771, 1680, 1597, 1539, 1491, 1445, 1340, 1246, 752.

参考例７９で得た2-(4-メトキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(1.23g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点179-181℃の無色結晶(914mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.85-3.15 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.73 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.89 (2H, d, J = 8.4Hz), 7.18 (2H, d, J = 8.4Hz), 7.73 (2H, s), 9.00-9.20 (2H, br).
元素分析 C₂₅H₃₀N₂O₃・HCl・0.5H₂Oとして
計算値：C, 66.43; H, 7.14; N, 6.20.
実験値：C, 66.41; H, 7.04; N, 6.06. 8- (5-{[2- (4-Methoxyphenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (4-Methoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 79 The title compound was obtained as colorless crystals (914 mg) with a melting point of 179-181 ° C. by the same procedure as in Example 1 using -8-yl) pentyl] carbamate tert-butyl (1.23 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.85-3.15 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.73 (3H, s), 3.99 (2H, t, J = 8.4Hz), 6.89 (2H, d, J = 8.4Hz), 7.18 (2H, d, J = 8.4Hz), 7.73 (2H , s), 9.00-9.20 (2H, br).
Elemental analysis Calculated as C ₂₅ H ₃₀ N ₂ O ₃ · HCl · 0.5H ₂ O: C, 66.43; H, 7.14; N, 6.20.
Experimental value: C, 66.41; H, 7.04; N, 6.06.

参考例８０で得た2-(4-クロロフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(941mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点193-195℃の無色結晶(708mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.75-3.25 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.31 (2H, d, J = 8.4Hz), 7.40 (2H, d, J = 8.4Hz), 7.73 (2H, s), 9.05-9.30 (2H, br).
元素分析 C₂₄H₂₇ClN₂O₂・HClとして
計算値：C, 64.43; H, 6.31; N, 6.26.
実験値：C, 64.07; H, 6.40; N, 6.07. 8- (5-{[2- (4-Chlorophenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

2- (4-Chlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- obtained in Reference Example 80 The title compound was obtained as colorless crystals (708 mg) with a melting point of 193-195 ° C. by the same procedure as in Example 1 using 8-yl) pentyl] carbamate tert-butyl (941 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.75-3.25 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.31 (2H, d, J = 8.4Hz), 7.40 (2H, d, J = 8.4Hz), 7.73 (2H, s), 9.05-9.30 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ .HCl: C, 64.43; H, 6.31; N, 6.26.
Experimental value: C, 64.07; H, 6.40; N, 6.07.

参考例８１で得た2-(3-クロロフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(1.19g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点157-159℃の無色結晶(972mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.60 (2H, t, J = 7.8Hz), 2.85-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.20-7.45 (4H, m), 7.73 (2H, s), 8.80-9.05 (2H, br). 8- (5-{[2- (3-Chlorophenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

2- (3-Chlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- obtained in Reference Example 81 The title compound was obtained as colorless crystals (972 mg) with a melting point of 157-159 ° C. by the same procedure as in Example 1 using 8-tert) butyl (pentyl) carbamate (1.19 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.60 (2H, t, J = 7.8Hz), 2.85-3.20 (10H, m), 3.18 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 7.20-7.45 (4H, m), 7.73 (2H, s), 8.80-9.05 (2H, br).

参考例８２で得た2-(2-ヒドロキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(637mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点112-113℃の無色結晶(530mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.85-3.10 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.98 (2H, t, J = 8.4Hz), 4.50-5.50 (1H, br), 6.73 (1H, dt, J = 7.5, 1.2Hz), 6.88 (1H, dd, J = 7.8, 1.2Hz), 7.00-7.10 (2H, m), 7.72 (1H, s), 7.73 (1H, s), 9.00-9.20 (2H, br).
元素分析 C₂₄H₂₈N₂O₃・HCl・2.0H₂Oとして
計算値：C, 61.99; H, 7.15; N, 6.02.
実験値：C, 61.97; H, 6.87; N, 5.88. 8- (5-{[2- (2-hydroxyphenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (2-hydroxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 82 The title compound was obtained as colorless crystals (530 mg) having a melting point of 112-113 ° C. by the same procedure as in Example 1 using -8-yl) pentyl] carbamate tert-butyl (637 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.85-3.10 (10H, m), 3.17 (2H, t, J = 8.4Hz), 3.98 (2H, t, J = 8.4Hz), 4.50-5.50 (1H, br), 6.73 (1H, dt, J = 7.5, 1.2Hz), 6.88 (1H, dd, J = 7.8, 1.2 Hz), 7.00-7.10 (2H, m), 7.72 (1H, s), 7.73 (1H, s), 9.00-9.20 (2H, br).
Elemental analysis _{C 24 H 28 N 2 O 3} · HCl · 2.0H 2 O Calculated: C, 61.99; H, 7.15 ; N, 6.02.
Experimental values: C, 61.97; H, 6.87; N, 5.88.

参考例８３で得た2-(2,6-ジクロロフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(1.08g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点172-174℃の無色結晶(618mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.90-3.10 (8H, m), 3.17 (2H, t, J = 8.4Hz), 3.25-3.35 (2H, m), 3.98 (2H, t, J = 8.4Hz), 7.33 (1H, dd, J = 8.7, 7.5Hz), 7.49 (2H, d, J = 7.5Hz), 7.72 (1H, s), 7.73 (1H, s), 9.25-9.50 (2H, br).
元素分析 C₂₄H₂₆Cl₂N₂O₂・HClとして
計算値：C, 59.82; H, 5.65; N, 5.81.
実験値：C, 59.48; H, 5.67; N, 5.53. 8- (5-{[2- (2,6-dichlorophenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

2- (2,6-dichlorophenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] obtained in Reference Example 83 The title compound was obtained as colorless crystals (618 mg) having a melting point of 172-174 ° C. by performing the same procedure as in Example 1 using quinolin-8-yl) pentyl] carbamate tert-butyl (1.08 g). .
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.90-3.10 (8H, m), 3.17 (2H, t, J = 8.4Hz), 3.25-3.35 (2H, m), 3.98 (2H, t, J = 8.4Hz), 7.33 (1H, dd, J = 8.7, 7.5Hz), 7.49 (2H, d, J = 7.5Hz) , 7.72 (1H, s), 7.73 (1H, s), 9.25-9.50 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₂₆ Cl ₂ N ₂ O ₂ .HCl: C, 59.82; H, 5.65; N, 5.81.
Experimental value: C, 59.48; H, 5.67; N, 5.53.

参考例８４で得た2-(2,3-ジメトキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(1.13g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点154-156℃の無色結晶(708mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.58 (2H, t, J = 7.8Hz), 2.90-3.10 (10H, m), 3.16 (2H, t, J = 8.4Hz), 3.73 (3H, s), 3.78 (3H, s), 3.97 (2H, t, J = 8.4Hz), 6.79 (1H, dd, J = 8.2, 1.8Hz), 6.94 (1H, dd, J = 8.0, 1.8Hz), 6.95-7.05 (1H, m), 7.71 (1H, s), 7.72 (1H, s), 8.80-9.10 (2H, br).
元素分析 C₂₆H₃₂N₂O₄・HCl・0.5H₂Oとして
計算値：C, 64.79; H, 7.11; N, 5.81.
実験値：C, 64.34; H, 7.03; N, 5.55. 8- (5-{[2- (2,3-dimethoxyphenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4- On hydrochloride

2- (2,3-Dimethoxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] obtained in Reference Example 84 ] Quinolin-8-yl) pentyl] carbamic acid tert-butyl (1.13 g) was used for the same operation as in Example 1 to obtain the title compound as colorless crystals (708 mg) having a melting point of 154-156 ° C. It was.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.58 (2H, t, J = 7.8Hz), 2.90-3.10 (10H, m), 3.16 (2H, t, J = 8.4Hz), 3.73 (3H, s), 3.78 (3H, s), 3.97 (2H, t, J = 8.4Hz), 6.79 (1H, dd, J = 8.2, 1.8Hz), 6.94 (1H, dd, J = 8.0, 1.8Hz), 6.95-7.05 (1H, m), 7.71 (1H, s), 7.72 (1H, s), 8.80-9.10 (2H, br).
Elemental analysis Calculated as C ₂₆ H ₃₂ N ₂ O ₄ · HCl · 0.5H ₂ O: C, 64.79; H, 7.11; N, 5.81.
Experimental value: C, 64.34; H, 7.03; N, 5.55.

参考例８５で得た5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル[2-(2-チエニル)エチル]カルバミン酸 tert-ブチル(1.44g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点167-169℃の無色結晶(700mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.90-3.05 (6H, m), 3.10-3.30 (6H, m), 3.98 (2H, t, J = 8.4Hz), 6.95-7.00 (2H, m), 7.40(1H, dd, J = 4.8, 1.5Hz), 7.72 (1H, s), 7.73 (1H, s), 9.10-9.30 (2H, br). 8- (5-{[2- (2-Thienyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl [2- ( The title compound was obtained as colorless crystals (700 mg) with a melting point of 167-169 ° C. by the same procedure as in Example 1 using tert-butyl 2-thienyl) ethyl] carbamate (1.44 g).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.90-3.05 (6H, m), 3.10-3.30 (6H, m) , 3.98 (2H, t, J = 8.4Hz), 6.95-7.00 (2H, m), 7.40 (1H, dd, J = 4.8, 1.5Hz), 7.72 (1H, s), 7.73 (1H, s), 9.10-9.30 (2H, br).

参考例８６で得た5-(2,3-ジヒドロ-1,4-ベンゾジオキシン-6-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(1.18g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点172-174℃の無色結晶(752mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.45-1.80 (4H, m), 2.90-3.15 (6H, m), 3.30-3.45 (6H, m), 3.80 (3H, s), 6.90 (1H, t, J = 7.4Hz), 6.99 (1H, d, J = 8.4Hz), 7.18 (1H, dd, J = 7.4, 1.8Hz), 7.20-7.30 (2H, m), 7.73 (1H, d, J = 1.5Hz), 7.80 (1H, dd, J = 8.1, 1.5Hz), 8.95-9.15 (2H, br). 1- (2,3-Dihydro-1,4-benzodioxin-6-yl) -5-{[2- (2-methoxyphenyl) ethyl] amino} -1-pentanone hydrochloride

Tert-Butyl 5- (2,3-dihydro-1,4-benzodioxin-6-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate (1.18 g) obtained in Reference Example 86 ) To give the title compound as colorless crystals (752 mg) having a melting point of 172-174 ° C. by the same procedure as in Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.45-1.80 (4H, m), 2.90-3.15 (6H, m), 3.30-3.45 (6H, m), 3.80 (3H, s), 6.90 (1H, t, J = 7.4Hz), 6.99 (1H, d, J = 8.4Hz), 7.18 (1H, dd, J = 7.4, 1.8Hz), 7.20-7.30 (2H, m), 7.73 (1H, d, J = 1.5Hz), 7.80 (1H, dd, J = 8.1, 1.5Hz), 8.95-9.15 (2H, br).

参考例８７で得た5-[3-(アミノスルホニル)-4-メトキシフェニル]-5-オキソペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(1.00g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点166-168℃の無色結晶(833mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.85-3.20 (8H, m), 3.98 (3H, s), 7.20-7.40 (8H, m), 8.20 (1H, dd, J = 8.8, 2.1Hz), 8.28 (1H, d, J = 2.1Hz), 8.80-9.10 (2H, br).
元素分析 C₂₀H₂₆N₂O₄S・HCl・0.5H₂Oとして
計算値：C, 55.10; H, 6.47; N, 6.43.
実験値：C, 55.08; H, 6.37; N, 6.28. 2-Methoxy-5- {5-[(2-phenylethyl) amino] pentanoyl} benzenesulfonamide hydrochloride

The same procedure as in Example 1 was carried out using tert-butyl 5- [3- (aminosulfonyl) -4-methoxyphenyl] -5-oxopentyl (2-phenylethyl) carbamate (1.00 g) obtained in Reference Example 87. The title compound was obtained as colorless crystals (833 mg) having a melting point of 166-168 ° C.
^{1 H NMR (300MHz, DMSO-} d 6) δ 1.60-1.80 (4H, m), 2.85-3.20 (8H, m), 3.98 (3H, s), 7.20-7.40 (8H, m), 8.20 (1H, dd, J = 8.8, 2.1Hz), 8.28 (1H, d, J = 2.1Hz), 8.80-9.10 (2H, br).
Elemental analysis Calculated as C ₂₀ H ₂₆ N ₂ O ₄ S · HCl · 0.5H ₂ O: C, 55.10; H, 6.47; N, 6.43.
Experimental value: C, 55.08; H, 6.37; N, 6.28.

参考例８８で得た5-[3-(アミノスルホニル)-4-メトキシフェニル]-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(740mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点139-141℃の無色結晶(504mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.85-3.10 (8H, m), 3.78 (3H, s), 3.98 (3H, s), 6.89 (1H, dt, J = 7.3, 1.5Hz), 6.98 (1H, d, J = 8.1Hz), 7.16 (1H, dd, J = 7.3, 1.5Hz), 7.20-7.25 (3H, m), 7.31 (1H, d, J = 8.7Hz), 8.20 (1H, dd, J = 8.7, 2.4Hz), 8.28 (1H, d, J = 2.4Hz), 8.80-9.05 (2H, br).
元素分析 C₂₁H₂₈N₂O₅S・HCl・0.5H₂Oとして
計算値：C, 54.13; H, 6.49; N, 6.01.
実験値：C, 54.71; H, 6.50; N, 5.86. 2-Methoxy-5- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) benzenesulfonamide hydrochloride

Using tert-butyl 5- [3- (aminosulfonyl) -4-methoxyphenyl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 88 (740 mg) The title compound was obtained as colorless crystals (504 mg) having a melting point of 139-141 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.85-3.10 (8H, m), 3.78 (3H, s), 3.98 (3H, s), 6.89 (1H, dt, J = 7.3, 1.5Hz), 6.98 (1H, d, J = 8.1Hz), 7.16 (1H, dd, J = 7.3, 1.5Hz), 7.20-7.25 (3H, m), 7.31 (1H, d, J = 8.7Hz), 8.20 (1H, dd, J = 8.7, 2.4Hz), 8.28 (1H, d, J = 2.4Hz), 8.80-9.05 (2H, br).
Elemental analysis Calculated as C ₂₁ H ₂₈ N ₂ O ₅ S · HCl · 0.5H ₂ O: C, 54.13; H, 6.49; N, 6.01.
Experimental value: C, 54.71; H, 6.50; N, 5.86.

参考例８９で得た5-[3-(アミノスルホニル)-4-メトキシフェニル]-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(1.00g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点161-163℃の無色結晶(845mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.90-3.20 (8H, m), 3.99 (3H, s), 7.20-7.50 (7H, m), 8.21 (1H, dd, J = 8.6, 2.1Hz), 8.30 (1H, d, J = 2.1Hz), 9.00-9.20 (2H, br).
元素分析 C₂₀H₂₅ClN₂O₄S・HClとして
計算値：C, 52.06; H, 5.68; N, 6.07.
実験値：C, 52.04; H, 5.72; N, 5.93. 5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2-methoxybenzenesulfonamide hydrochloride

Using tert-butyl 5- [3- (aminosulfonyl) -4-methoxyphenyl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate obtained in Reference Example 89 (1.00 g) The title compound was obtained as colorless crystals (845 mg) having a melting point of 161-163 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.90-3.20 (8H, m), 3.99 (3H, s), 7.20-7.50 (7H, m), 8.21 (1H, dd, J = 8.6, 2.1Hz), 8.30 (1H, d, J = 2.1Hz), 9.00-9.20 (2H, br).
Elemental analysis Calculated as C ₂₀ H ₂₅ ClN ₂ O ₄ S · HCl: C, 52.06; H, 5.68; N, 6.07.
Experimental values: C, 52.04; H, 5.72; N, 5.93.

参考例６６で得た5-(5-クロロペンタノイル)-2-メトキシベンゼンスルホンアミド(800mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(533mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(126mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.45-1.80 (4H, m), 2.33 (3H, s), 2.40-2.65 (4H, m), 2.80-3.00 (4H, m), 4.10 (3H, s), 4.50-5.50 (2H, br), 7.00-7.40(5H, m), 8.10-8.20(1H, m), 8.20-8.30(1H, m). 5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2-methoxybenzenesulfonamide hydrochloride

Using 5- (5-chloropentanoyl) -2-methoxybenzenesulfonamide (800 mg) and N- [2- (2-chlorophenyl) ethyl] -N-methylamine (533 mg) obtained in Reference Example 66, The same operation as in Example 9 was performed to obtain the title compound (126 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.45-1.80 (4H, m), 2.33 (3H, s), 2.40-2.65 (4H, m), 2.80-3.00 (4H, m), 4.10 (3H , s), 4.50-5.50 (2H, br), 7.00-7.40 (5H, m), 8.10-8.20 (1H, m), 8.20-8.30 (1H, m).

参考例９０で得た5-{3-[(イソプロピルアミノ)スルホニル]-4-メトキシフェニル}-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(1.36g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点164-166℃の無色結晶(601mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 0.96 (6H, d, J = 6.6Hz), 1.60-1.80 (4H, m), 2.85-3.40 (9H, m), 3.80 (3H, s), 4.01 (3H, s), 6.85-7.05 (2H, m), 7.15-7.45 (4H, m), 8.25 (1H, dd, J = 8.4, 2.2Hz), 8.31 (1H, d, J = 2.2Hz), 8.90-9.10 (2H, br).
元素分析 C₂₄H₃₄N₂O₅S・HClとして
計算値：C, 57.76; H, 7.07; N, 5.61.
実験値：C, 57.41; H, 7.21; N, 5.51. N-isopropyl-2-methoxy-5- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) benzenesulfonamide hydrochloride

5- {3-[(isopropylamino) sulfonyl] -4-methoxyphenyl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl (1.36 g) obtained in Reference Example 90 And the title compound was obtained as colorless crystals (601 mg) having a melting point of 164-166 ° C. by performing the same operations as in Example 1.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 0.96 (6H, d, J = 6.6Hz), 1.60-1.80 (4H, m), 2.85-3.40 (9H, m), 3.80 (3H, s), 4.01 (3H, s), 6.85-7.05 (2H, m), 7.15-7.45 (4H, m), 8.25 (1H, dd, J = 8.4, 2.2Hz), 8.31 (1H, d, J = 2.2Hz), 8.90-9.10 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₃₄ N ₂ O ₅ S · HCl: C, 57.76; H, 7.07; N, 5.61.
Experimental value: C, 57.41; H, 7.21; N, 5.51.

参考例９１で得た2-(2-クロロフェニル)エチル(5-{3-[(イソプロピルアミノ)スルホニル]-4-メトキシフェニル}-5-オキソペンチル)カルバミン酸 tert-ブチル(1.28g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点179-181℃の無色結晶(1.00g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 0.96 (6H, d, J = 6.6Hz), 1.60-1.80 (4H, m), 2.90-3.50 (9H, m), 4.01 (3H, s), 7.25-7.50 (6H, m), 8.25 (1H, dd, J = 8.4, 2.2Hz), 8.32 (1H, d, J = 2.2Hz), 9.00-9.25 (2H, br).
元素分析 C₂₃H₃₁ClN₂O₄S・HClとして
計算値：C, 54.87; H, 6.41; N, 5.56.
実験値：C, 54.67; H, 6.33; N, 5.33. 5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -N-isopropyl-2-methoxybenzenesulfonamide hydrochloride

Using tert-butyl 2- (2-chlorophenyl) ethyl (5- {3-[(isopropylamino) sulfonyl] -4-methoxyphenyl} -5-oxopentyl) carbamate (1.28 g) obtained in Reference Example 91 The title compound was obtained as colorless crystals (1.00 g) with a melting point of 179-181 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 0.96 (6H, d, J = 6.6Hz), 1.60-1.80 (4H, m), 2.90-3.50 (9H, m), 4.01 (3H, s), 7.25 -7.50 (6H, m), 8.25 (1H, dd, J = 8.4, 2.2Hz), 8.32 (1H, d, J = 2.2Hz), 9.00-9.25 (2H, br).
Elemental analysis Calculated as C ₂₃ H ₃₁ ClN ₂ O ₄ S · HCl: C, 54.87; H, 6.41; N, 5.56.
Experimental values: C, 54.67; H, 6.33; N, 5.33.

参考例６７で得た5-(5-クロロペンタノイル)-N-イソプロピル-2-メトキシベンゼンスルホンアミド(800mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(470mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(536mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.06 (6H, d, J = 6.6Hz), 1.50-1.80 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.2Hz), 2.55-2.70 (2H, m), 2.85-2.90 (2H, m), 2.98 (2H, t, J = 7.2Hz), 3.30-3.55 (1H, m), 4.07 (3H, s), 4.85-4.95 (1H, m), 7.05-7.35 (5H, m), 8.19 (1H, dd, J = 8.8, 2.2Hz), 8.50 (1H, d, J = 2.2Hz).
元素分析 C₂₄H₃₃ClN₂O₄S・HCl・0.5H₂Oとして
計算値：C, 54.75; H, 6.70; N, 5.32.
実験値：C, 54.45; H, 6.94; N, 5.11. 5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -N-isopropyl-2-methoxybenzenesulfonamide hydrochloride

5- (5-Chloropentanoyl) -N-isopropyl-2-methoxybenzenesulfonamide (800 mg) and N- [2- (2-chlorophenyl) ethyl] -N-methylamine (470 mg) obtained in Reference Example 67 By using the same procedure as in Example 9, the title compound (536 mg) was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.06 (6H, d, J = 6.6 Hz), 1.50-1.80 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.2 Hz), 2.55-2.70 (2H, m), 2.85-2.90 (2H, m), 2.98 (2H, t, J = 7.2Hz), 3.30-3.55 (1H, m), 4.07 (3H, s), 4.85 -4.95 (1H, m), 7.05-7.35 (5H, m), 8.19 (1H, dd, J = 8.8, 2.2Hz), 8.50 (1H, d, J = 2.2Hz).
Elemental analysis Calculated as C ₂₄ H ₃₃ ClN ₂ O ₄ S · HCl · 0.5H ₂ O: C, 54.75; H, 6.70; N, 5.32.
Experimental value: C, 54.45; H, 6.94; N, 5.11.

参考例９２で得た5-[7-(アミノスルホニル)-2,3-ジヒドロ-1-ベンゾフラン-5-イル]-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(990mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(781mg) を淡黄色非晶状粉末として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.50-1.90 (4H, m), 2.95-3.25 (8H, m), 3.41 (2H, t, J = 8.6Hz), 3.89 (3H, s), 4.91 (2H, t, J = 8.6Hz), 6.90-7.10 (2H, m), 7.20-7.40 (2H, m), 7.50 (2H, s), 8.71 (1H, s), 8.20 (1H, s), 8.95-9.25 (2H, br).
元素分析 C₂₂H₂₈N₂O₅S・HCl・0.5H₂Oとして
計算値：C, 55.28; H, 6.33; N, 5.86.
実験値：C, 55.48; H, 6.50; N, 5.61. 5- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- [7- (Aminosulfonyl) -2,3-dihydro-1-benzofuran-5-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamic acid tert- obtained in Reference Example 92 The same operation as in Example 1 was carried out using butyl (990 mg) to give the title compound (781 mg) as a pale yellow amorphous powder.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.50-1.90 (4H, m), 2.95-3.25 (8H, m), 3.41 (2H, t, J = 8.6Hz), 3.89 (3H, s), 4.91 (2H, t, J = 8.6Hz), 6.90-7.10 (2H, m), 7.20-7.40 (2H, m), 7.50 (2H, s), 8.71 (1H, s), 8.20 (1H, s), 8.95-9.25 (2H, br).
Elemental analysis Calculated as C ₂₂ H ₂₈ N ₂ O ₅ S · HCl · 0.5H ₂ O: C, 55.28; H, 6.33; N, 5.86.
Experimental values: C, 55.48; H, 6.50; N, 5.61.

参考例９３で得た5-[7-(アミノスルホニル)-2,3-ジヒドロ-1-ベンゾフラン-5-イル]-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(900mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点168-170℃の無色結晶(743mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.85-3.20 (8H, m), 3.32 (2H, t, J = 8.6Hz), 4.82 (2H, t, J = 8.6Hz), 7.25-7.55 (6H, m), 8.11 (1H, s), 8.12 (1H, s), 9.10-9.40 (2H, br).
元素分析 C₂₁H₂₅ClN₂O₄S・HCl・0.2H₂Oとして
計算値：C, 52.88; H, 5.58; N, 5.87.
実験値：C, 52.93; H, 5.42; N, 5.66. 5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

Tert-Butyl 5- [7- (aminosulfonyl) -2,3-dihydro-1-benzofuran-5-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate obtained in Reference Example 93 (900 mg) was used in the same manner as in Example 1 to obtain the title compound as colorless crystals (743 mg) having a melting point of 168-170 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.85-3.20 (8H, m), 3.32 (2H, t, J = 8.6Hz), 4.82 (2H, t, J = 8.6Hz), 7.25-7.55 (6H, m), 8.11 (1H, s), 8.12 (1H, s), 9.10-9.40 (2H, br).
Elemental analysis Calculated as C ₂₁ H ₂₅ ClN ₂ O ₄ S · HCl · 0.2H ₂ O: C, 52.88; H, 5.58; N, 5.87.
Experimental value: C, 52.93; H, 5.42; N, 5.66.

参考例７０で得た5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(1.00g) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(625mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(527mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.50-1.80 (4H, m), 2.36 (3H, s), 2.52 (2H, t, J = 7.2Hz), 2.60-2.65 (2H, m), 2.75-2.80 (2H, m), 2.91 (2H, t, J = 7.2Hz), 3.00-5.00 (2H, br), 3.04 (2H, t, J = 8.7Hz), 3.81 (3H, s), 4.87 (2H, t, J = 8.7Hz), 6.80-6.90 (2H, m), 7.10-7.20 (2H, m), 7.98 (1H, s), 8.19 (1H, s).
元素分析 C₂₃H₃₀N₂O₅S・HCl・0.5H₂Oとして
計算値：C, 56.14; H, 6.56; N, 5.69.
実験値：C, 55.83; H, 6.81; N, 5.45. 5- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide (1.00 g) and N- [2- (2-methoxyphenyl) ethyl] -N obtained in Reference Example 70 -The title compound (527mg) was obtained as a pale yellow amorphous powder by carrying out the same operation as in Example 9 using methylamine (625mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.50-1.80 (4H, m), 2.36 (3H, s), 2.52 (2H, t, J = 7.2 Hz), 2.60-2.65 (2H, m), 2.75-2.80 (2H, m), 2.91 (2H, t, J = 7.2Hz), 3.00-5.00 (2H, br), 3.04 (2H, t, J = 8.7Hz), 3.81 (3H, s), 4.87 (2H, t, J = 8.7Hz), 6.80-6.90 (2H, m), 7.10-7.20 (2H, m), 7.98 (1H, s), 8.19 (1H, s).
Elemental analysis Calculated as C ₂₃ H ₃₀ N ₂ O ₅ S · HCl · 0.5H ₂ O: C, 56.14; H, 6.56; N, 5.69.
Experimental values: C, 55.83; H, 6.81; N, 5.45.

参考例７０で得た5-(5-クロロペンタノイル)-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(800mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(513mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(519mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.45-1.80 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.2Hz), 2.55-2.65 (2H, m), 2.80-2.90 (4H, m), 3.32 (2H, t, J = 8.7Hz), 3.50-5.50 (2H, br), 4.88 (2H, t, J = 8.7Hz), 7.10-7.35 (4H, m), 7.99 (1H, s), 8.18 (1H, s). 5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide (800 mg) and N- [2- (2-chlorophenyl) ethyl] -N-methyl obtained in Reference Example 70 The same operation as in Example 9 was performed using amine (513 mg) to give the title compound (519 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.45-1.80 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.2 Hz), 2.55-2.65 (2H, m), 2.80-2.90 (4H, m), 3.32 (2H, t, J = 8.7Hz), 3.50-5.50 (2H, br), 4.88 (2H, t, J = 8.7Hz), 7.10-7.35 (4H, m) , 7.99 (1H, s), 8.18 (1H, s).

参考例９４で得た5-{7-[(イソプロピルアミノ)スルホニル]-2,3-ジヒドロ-1-ベンゾフラン-5-イル}-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(1.00g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点157-159℃の無色結晶(707mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 0.99 (6H, d, J = 6.6Hz), 1.60-1.85 (4H, m), 2.80-3.15 (7H, m), 3.20-3.50 (4H, m), 3.80 (3H, s), 4.82 (2H, t, J = 8.8Hz), 6.85-7.05 (2H, m), 7.15-7.30 (2H, m), 7.60 (1H, d, J = 7.6Hz), 8.10 (2H, s), 8.90-9.15 (2H, br).
元素分析 C₂₅H₃₄N₂O₅S・HClとして
計算値：C, 58.75; H, 6.90; N, 5.48.
実験値：C, 58.33; H, 6.92; N, 5.31. N-isopropyl-5- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- {7-[(Isopropylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamine obtained in Reference Example 94 Using the acid tert-butyl (1.00 g), the title compound was obtained as colorless crystals (707 mg) having a melting point of 157-159 ° C. by the same procedure as in Example 1.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 0.99 (6H, d, J = 6.6Hz), 1.60-1.85 (4H, m), 2.80-3.15 (7H, m), 3.20-3.50 (4H, m) , 3.80 (3H, s), 4.82 (2H, t, J = 8.8Hz), 6.85-7.05 (2H, m), 7.15-7.30 (2H, m), 7.60 (1H, d, J = 7.6Hz), 8.10 (2H, s), 8.90-9.15 (2H, br).
Elemental analysis Calculated as C ₂₅ H ₃₄ N ₂ O ₅ S · HCl: C, 58.75; H, 6.90; N, 5.48.
Experimental value: C, 58.33; H, 6.92; N, 5.31.

参考例９５で得た2-(2-クロロフェニル)エチル(5-{7-[(イソプロピルアミノ)スルホニル]-2,3-ジヒドロ-1-ベンゾフラン-5-イル}-5-オキソペンチル)カルバミン酸 tert-ブチル(2.10g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点149-151℃の無色結晶(2.16g)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 0.99 (6H, d, J = 6.6Hz), 1.60-1.85 (4H, m), 2.90-3.20 (7H, m), 3.25-3.45 (4H, m), 4.82 (2H, t, J = 8.8Hz), 7.30-7.50 (4H, m), 7.60 (1H, d, J = 7.6Hz), 8.10 (2H, s), 8.90-9.30 (2H, br).
元素分析 C₂₄H₃₁ClN₂O₄S・HClとして
計算値：C, 55.92; H, 6.26; N, 5.43.
実験値：C, 55.78; H, 5.99; N, 5.26. 5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -N-isopropyl-2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

2- (2-Chlorophenyl) ethyl (5- {7-[(isopropylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl) carbamic acid obtained in Reference Example 95 The title compound was obtained as colorless crystals (2.16 g) having a melting point of 149-151 ° C. by the same procedure as in Example 1 using tert-butyl (2.10 g).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 0.99 (6H, d, J = 6.6Hz), 1.60-1.85 (4H, m), 2.90-3.20 (7H, m), 3.25-3.45 (4H, m) , 4.82 (2H, t, J = 8.8Hz), 7.30-7.50 (4H, m), 7.60 (1H, d, J = 7.6Hz), 8.10 (2H, s), 8.90-9.30 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₃₁ ClN ₂ O ₄ S · HCl: C, 55.92; H, 6.26; N, 5.43.
Experimental value: C, 55.78; H, 5.99; N, 5.26.

参考例７１で得た5-(5-クロロペンタノイル)-N-イソプロピル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(1.00g) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(551mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(470mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.10 (6H, d, J = 6.6Hz), 1.45-1.80 (4H, m), 2.32 (3H, s), 2.46 (2H, t, J = 7.2Hz), 2.50-2.60 (2H, m), 2.70-2.85 (2H, m), 2.96 (2H, t, J = 7.2Hz), 3.33 (2H, t, J = 8.8Hz), 3.35-3.55 (1H, m), 3.82 (3H, s), 4.65-4.80 (1H, m), 4.86 (2H, t, J = 8.8Hz), 6.80-6.90 (2H, m), 7.10-7.20 (2H, m), 8.04 (1H, d, J = 2.0Hz), 8.24 (1H, d, J = 2.0Hz).
元素分析 C₂₆H₃₆N₂O₅S・HCl・0.5H₂Oとして
計算値：C, 58.47; H, 7.17; N, 5.24.
実験値：C, 58.53; H, 7.31; N, 5.15. N-isopropyl-5- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -N-isopropyl-2,3-dihydro-1-benzofuran-7-sulfonamide (1.00 g) and N- [2- (2-methoxyphenyl) obtained in Reference Example 71 The title compound (470 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using ethyl] -N-methylamine (551 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.10 (6H, d, J = 6.6 Hz), 1.45-1.80 (4H, m), 2.32 (3H, s), 2.46 (2H, t, J = 7.2 Hz), 2.50-2.60 (2H, m), 2.70-2.85 (2H, m), 2.96 (2H, t, J = 7.2Hz), 3.33 (2H, t, J = 8.8Hz), 3.35-3.55 (1H , m), 3.82 (3H, s), 4.65-4.80 (1H, m), 4.86 (2H, t, J = 8.8Hz), 6.80-6.90 (2H, m), 7.10-7.20 (2H, m), 8.04 (1H, d, J = 2.0Hz), 8.24 (1H, d, J = 2.0Hz).
Elemental analysis Calculated as C ₂₆ H ₃₆ N ₂ O ₅ S · HCl · 0.5H ₂ O: C, 58.47; H, 7.17; N, 5.24.
Experimental values: C, 58.53; H, 7.31; N, 5.15.

参考例７１で得た5-(5-クロロペンタノイル)-N-イソプロピル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(1.00g) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(565mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(490mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.10 (6H, d, J = 6.6Hz), 1.45-1.80 (4H, m), 2.31 (3H, s), 2.48 (2H, t, J = 7.2Hz), 2.55-2.70 (2H, m), 2.80-3.00 (4H, m), 3.33 (2H, t, J = 8.8Hz), 3.35-3.60 (1H, m), 4.68 (1H, d, J = 7.4Hz), 4.86 (2H, t, J = 8.8Hz), 7.10-7.40 (4H, m), 8.04 (1H, d, J = 2.0Hz), 8.24 (1H, d, J = 2.0Hz).
元素分析 C₂₅H₃₃ClN₂O₄S・HCl・0.5H₂Oとして
計算値：C, 55.76; H, 6.55; N, 5.20.
実験値：C, 55.38; H, 6.72; N, 5.07. 5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -N-isopropyl-2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -N-isopropyl-2,3-dihydro-1-benzofuran-7-sulfonamide (1.00 g) and N- [2- (2-chlorophenyl) ethyl obtained in Reference Example 71 The title compound (490 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -N-methylamine (565 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.10 (6H, d, J = 6.6 Hz), 1.45-1.80 (4H, m), 2.31 (3H, s), 2.48 (2H, t, J = 7.2 Hz), 2.55-2.70 (2H, m), 2.80-3.00 (4H, m), 3.33 (2H, t, J = 8.8Hz), 3.35-3.60 (1H, m), 4.68 (1H, d, J = 7.4Hz), 4.86 (2H, t, J = 8.8Hz), 7.10-7.40 (4H, m), 8.04 (1H, d, J = 2.0Hz), 8.24 (1H, d, J = 2.0Hz).
Elemental analysis Calculated as C ₂₅ H ₃₃ ClN ₂ O ₄ S · HCl · 0.5H ₂ O: C, 55.76; H, 6.55; N, 5.20.
Experimental value: C, 55.38; H, 6.72; N, 5.07.

参考例９６で得た5-[8-(アミノスルホニル)-2,2-ジメチル-3,4-ジヒドロ-2H-クロメン-6-イル]-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(715mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(568mg) を無色非晶状粉末として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.40 (6H, s), 1.60-1.80 (4H, m), 1.87 (2H, t, J = 6.6Hz), 2.88 (2H, t, J = 6.6Hz), 2.90-3.20 (8H, m), 7.01 (2H, s), 7.25-7.50 (4H, m), 7.39 (1H, d, J = 2.1Hz), 8.14 (1H, d, J = 2.1Hz), 9.10-9.30 (2H, br).
元素分析 C₂₄H₃₁ClN₂O₄S・HCl・0.5H₂Oとして
計算値：C, 54.96; H, 6.34; N, 5.34.
実験値：C, 55.00; H, 6.36; N, 5.11. 6- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2,2-dimethyl-8-chromansulfonamide hydrochloride

5- [8- (Aminosulfonyl) -2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl obtained in Reference Example 96 The title compound (568 mg) was obtained as a colorless amorphous powder by the same procedure as in Example 1 using tert-butyl carbamate (715 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.40 (6H, s), 1.60-1.80 (4H, m), 1.87 (2H, t, J = 6.6Hz), 2.88 (2H, t, J = 6.6Hz ), 2.90-3.20 (8H, m), 7.01 (2H, s), 7.25-7.50 (4H, m), 7.39 (1H, d, J = 2.1Hz), 8.14 (1H, d, J = 2.1Hz) , 9.10-9.30 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₃₁ ClN ₂ O ₄ S · HCl · 0.5H ₂ O: C, 54.96; H, 6.34; N, 5.34.
Experimental value: C, 55.00; H, 6.36; N, 5.11.

参考例９７で得た5-[8-(アミノスルホニル)-2,3-ジヒドロ-1,4-ベンゾジオキシン-6-イル]-5-オキソペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(1.05g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点152-154℃の無色結晶(832mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.85-3.20 (8H, m), 4.30-4.40 (2H, m), 4.40-4.50 (2H, m), 7.20-7.40 (7H, m), 7.69 (1H, d, J = 2.1Hz), 7.89 (1H, d, J = 2.1Hz), 8.95-9.20 (2H, br).
元素分析 C₂₁H₂₆N₂O₅S・HClとして
計算値：C, 55.32; H, 6.19; N, 6.14.
実験値：C, 55.15; H, 6.06; N, 6.00. 7- {5-[(2-Phenylethyl) amino] pentanoyl} -2,3-dihydro-1,4-benzodioxin-5-sulfonamide hydrochloride

Tert-Butyl 5- [8- (aminosulfonyl) -2,3-dihydro-1,4-benzodioxin-6-yl] -5-oxopentyl (2-phenylethyl) carbamate obtained in Reference Example 97 The title compound was obtained as colorless crystals (832 mg) with a melting point of 152-154 ° C. by performing the same operation as in Example 1 using 1.05 g).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.85-3.20 (8H, m), 4.30-4.40 (2H, m), 4.40-4.50 (2H, m), 7.20- 7.40 (7H, m), 7.69 (1H, d, J = 2.1Hz), 7.89 (1H, d, J = 2.1Hz), 8.95-9.20 (2H, br).
Elemental analysis Calculated as C ₂₁ H ₂₆ N ₂ O ₅ S · HCl: C, 55.32; H, 6.19; N, 6.14.
Experimental value: C, 55.15; H, 6.06; N, 6.00.

参考例９８で得た5-[8-(アミノスルホニル)-2,3-ジヒドロ-1,4-ベンゾジオキシン-6-イル]-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(820mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点166-168℃の無色結晶(632mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.85-3.10 (8H, m), 3.80 (3H, s), 4.30-4.40 (2H, m), 4.40-4.50 (2H, m), 6.90 (1H, t, J = 7.5Hz), 6.99 (1H, d, J = 8.1Hz), 7.17 (1H, d, J = 7.5Hz), 7.25 (1H, t, J = 7.5Hz), 7.36 (2H, s), 7.69 (1H, d, J = 2.1Hz), 7.88 (1H, d, J = 2.1Hz), 8.80-9.15 (2H, br).
元素分析 C₂₂H₂₈ClN₂O₆S・HClとして
計算値：C, 54.48; H, 6.03; N, 5.78.
実験値：C, 54.12; H, 6.13; N, 5.64. 7- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1,4-benzodioxin-5-sulfonamide hydrochloride

5- [8- (Aminosulfonyl) -2,3-dihydro-1,4-benzodioxin-6-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamine obtained in Reference Example 98 The title compound was obtained as colorless crystals (632 mg) having a melting point of 166-168 ° C. by conducting the same operation as in Example 1 using tert-butyl acid (820 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.85-3.10 (8H, m), 3.80 (3H, s), 4.30-4.40 (2H, m), 4.40-4.50 ( 2H, m), 6.90 (1H, t, J = 7.5Hz), 6.99 (1H, d, J = 8.1Hz), 7.17 (1H, d, J = 7.5Hz), 7.25 (1H, t, J = 7.5 Hz), 7.36 (2H, s), 7.69 (1H, d, J = 2.1Hz), 7.88 (1H, d, J = 2.1Hz), 8.80-9.15 (2H, br).
Elemental analysis Calculated as C ₂₂ H ₂₈ ClN ₂ O ₆ S · HCl: C, 54.48; H, 6.03; N, 5.78.
Experimental values: C, 54.12; H, 6.13; N, 5.64.

参考例９９で得た5-[8-(アミノスルホニル)-2,3-ジヒドロ-1,4-ベンゾジオキシン-6-イル]-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(1.08g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点178-180℃の無色結晶(850mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.90-3.20 (8H, m), 4.30-4.40 (2H, m), 4.40-4.50 (2H, m), 7.25-7.50 (6H, m), 7.69 (1H, d, J = 2.1Hz), 7.88 (1H, d, J = 2.1Hz), 8.95-9.25 (2H, br).
元素分析 C₂₁H₂₅ClN₂O₅S・HCl・H₂Oとして
計算値：C, 49.71; H, 5.56; N, 5.52.
実験値：C, 49.72; H, 5.61; N, 5.35. 7- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1,4-benzodioxin-5-sulfonamide hydrochloride

5- [8- (Aminosulfonyl) -2,3-dihydro-1,4-benzodioxin-6-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamic acid obtained in Reference Example 99 The title compound was obtained as colorless crystals (850 mg) having a melting point of 178-180 ° C. by carrying out the same operation as in Example 1 using tert-butyl (1.08 g).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.90-3.20 (8H, m), 4.30-4.40 (2H, m), 4.40-4.50 (2H, m), 7.25- 7.50 (6H, m), 7.69 (1H, d, J = 2.1Hz), 7.88 (1H, d, J = 2.1Hz), 8.95-9.25 (2H, br).
Elemental analysis Calculated as C ₂₁ H ₂₅ ClN ₂ O ₅ S · HCl · H ₂ O: C, 49.71; H, 5.56; N, 5.52.
Experimental value: C, 49.72; H, 5.61; N, 5.35.

参考例７５で得た5-クロロ-1-(2,3-ジヒドロ-1,4-ベンゾジオキシン-6-イル)-1-ペンタノン(1.00g) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(565mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(490mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.45-1.75 (4H, m), 2.31 (3H, s), 2.45 (2H, t, J = 7.2Hz), 2.50-2.65 (2H, m), 2.80-2.95 (4H, m), 4.00-5.50 (2H, br), 4.30-4.40 (2H, m), 4.35-4.40 (2H, m), 7.05-7.35 (4H, m), 7.63 (1H, s), 7.98 (1H, s). 7- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1,4-benzodioxin-5-sulfonamide hydrochloride

5-Chloro-1- (2,3-dihydro-1,4-benzodioxin-6-yl) -1-pentanone (1.00 g) and N- [2- (2-chlorophenyl) ethyl obtained in Reference Example 75 The title compound (490 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -N-methylamine (565 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.45-1.75 (4H, m), 2.31 (3H, s), 2.45 (2H, t, J = 7.2 Hz), 2.50-2.65 (2H, m), 2.80-2.95 (4H, m), 4.00-5.50 (2H, br), 4.30-4.40 (2H, m), 4.35-4.40 (2H, m), 7.05-7.35 (4H, m), 7.63 (1H, s ), 7.98 (1H, s).

参考例１００で得た5-{4-メトキシ-3-[(メチルスルホニル)アミノ]フェニル}-5-オキソペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(1.32g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点131-133℃の無色結晶(945mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.55-1.75(4H, m), 2.85-3.20(8H, m), 2.96(3H, s), 3.89(3H, s), 7.15-7.40(6H, m), 7.80-7.90(2H, m), 8.85-9.15(2H, br), 9.14(1H, s).
元素分析 C₂₁H₂₈N₂O₄S・HCl・0.5H₂Oとして
計算値：C, 56.05; H, 6.72; N, 6.23.
実験値：C, 56.18; H, 6.62; N, 6.25. N- (2-methoxy-5- {5-[(2-phenylethyl) amino] pentanoyl} phenyl) methanesulfonamide hydrochloride

Example 5 Using 5- {4-methoxy-3-[(methylsulfonyl) amino] phenyl} -5-oxopentyl (2-phenylethyl) carbamate tert-butyl (1.32 g) obtained in Reference Example 100 The title compound was obtained as colorless crystals (945 mg) having a melting point of 131-133 ° C. by performing the same operation as in 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.55-1.75 (4H, m), 2.85-3.20 (8H, m), 2.96 (3H, s), 3.89 (3H, s), 7.15-7.40 (6H, m), 7.80-7.90 (2H, m), 8.85-9.15 (2H, br), 9.14 (1H, s).
Elemental analysis Calculated as C ₂₁ H ₂₈ N ₂ O ₄ S · HCl · 0.5H ₂ O: C, 56.05; H, 6.72; N, 6.23.
Experimental value: C, 56.18; H, 6.62; N, 6.25.

参考例１０１で得た5-{4-メトキシ-3-[(メチルスルホニル)アミノ]フェニル}-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(550mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点129-131℃の無色結晶(374mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.75(4H, m), 2.90-3.10(8H, m), 2.98(3H, s), 3.80(3H, s), 3.92(3H, s), 6.91(1H, t, J = 7.5Hz), 7.00(1H, d, J = 8.1Hz), 7.15-7.30(3H, m), 7.86(1H, d, J = 1.8Hz), 7.89(1H, dd, J = 8.5, 1.8Hz), 8.85-9.05(2H, br), 9.15(1H, s).
元素分析 C₂₂H₃₀N₂O₅S・HCl・0.5H₂Oとして
計算値：C, 55.05; H, 6.72; N, 5.84.
実験値：C, 55.20; H, 6.44; N, 5.80. N- [2-methoxy-5- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) phenyl] methanesulfonamide hydrochloride

Using tert-butyl (550 mg) of 5- {4-methoxy-3-[(methylsulfonyl) amino] phenyl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate obtained in Reference Example 101 The title compound was obtained as colorless crystals (374 mg) with a melting point of 129-131 ° C. by carrying out the same operation as in Example 1.
^{1 H NMR (300MHz, DMSO-} d 6) δ 1.60-1.75 (4H, m), 2.90-3.10 (8H, m), 2.98 (3H, s), 3.80 (3H, s), 3.92 (3H, s) , 6.91 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 8.1Hz), 7.15-7.30 (3H, m), 7.86 (1H, d, J = 1.8Hz), 7.89 (1H, dd, J = 8.5, 1.8Hz), 8.85-9.05 (2H, br), 9.15 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₃₀ N ₂ O ₅ S · HCl · 0.5H ₂ O: C, 55.05; H, 6.72; N, 5.84.
Experimental values: C, 55.20; H, 6.44; N, 5.80.

参考例１０２で得た2-(2-クロロフェニル)エチル(5-{4-メトキシ-3-[(メチルスルホニル)アミノ]フェニル}-5-オキソペンチル)カルバミン酸 tert-ブチル(1.52g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点133-135℃の無色結晶(1.03g)として得た。
¹H NMR (300MHz, CDCl₃) δ 1.75-2.10 (4H, m), 2.95-3.15 (4H, m), 3.00 (3H, s), 3.20-3.30 (2H, m), 3.35-3.45 (2H, m), 3.96 (3H, s), 6.92 (1H, s), 6.94 (1H, d, J = 8.4Hz), 7.10-7.40 (4H, m), 7.75 (1H, dd, J = 5.7, 1.4Hz), 8.04 (1H, d, J = 1.4Hz), 9.65-9.80 (2H, br).
元素分析 C₂₁H₂₇ClN₂O₄S・HCl・0.5H₂Oとして
計算値：C, 52.07; H, 6.03; N, 5.78.
実験値：C, 52.43; H, 5.78; N, 5.81. N- [5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2-methoxyphenyl] methanesulfonamide hydrochloride

Using tert-butyl 2- (2-chlorophenyl) ethyl (5- {4-methoxy-3-[(methylsulfonyl) amino] phenyl} -5-oxopentyl) carbamate obtained in Reference Example 102 (1.52 g) The title compound was obtained as colorless crystals (1.03 g) with a melting point of 133-135 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (300MHz, CDCl ₃ ) δ 1.75-2.10 (4H, m), 2.95-3.15 (4H, m), 3.00 (3H, s), 3.20-3.30 (2H, m), 3.35-3.45 (2H, m), 3.96 (3H, s), 6.92 (1H, s), 6.94 (1H, d, J = 8.4Hz), 7.10-7.40 (4H, m), 7.75 (1H, dd, J = 5.7, 1.4Hz ), 8.04 (1H, d, J = 1.4Hz), 9.65-9.80 (2H, br).
Elemental analysis Calculated as C ₂₁ H ₂₇ ClN ₂ O ₄ S · HCl · 0.5H ₂ O: C, 52.07; H, 6.03; N, 5.78.
Experimental value: C, 52.43; H, 5.78; N, 5.81.

参考例１０３で得た6-{4-メトキシ-3-[(メチルスルホニル)アミノ]フェニル}-6-オキソヘキシル(2-フェニルエチル)カルバミン酸 tert-ブチル(918mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点136-138℃の無色結晶(751mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45(2H, m), 1.55-1.75(4H, m), 2.85-3.10(8H, m), 2.98(3H, s), 3.92(3H, s), 7.15-7.40(6H, m), 7.80-7.90(2H, m), 8.95-9.20(2H, br), 9.16(1H, s).
元素分析 C₂₂H₃₀N₂O₄S・HCl・1.5H₂Oとして
計算値：C, 54.82; H, 7.11; N, 5.81.
実験値：C, 55.19; H, 7.34; N, 5.72. N- (2-methoxy-5- {6-[(2-phenylethyl) amino] hexanoyl} phenyl) methanesulfonamide hydrochloride

Example 1 Using tert-butyl 6- {4-methoxy-3-[(methylsulfonyl) amino] phenyl} -6-oxohexyl (2-phenylethyl) carbamate (918 mg) obtained in Reference Example 103 The title compound was obtained as colorless crystals (751 mg) having a melting point of 136-138 ° C. by carrying out the same operation as in.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.85-3.10 (8H, m), 2.98 (3H, s), 3.92 (3H, s), 7.15-7.40 (6H, m), 7.80-7.90 (2H, m), 8.95-9.20 (2H, br), 9.16 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₃₀ N ₂ O ₄ S · HCl · 1.5H ₂ O: C, 54.82; H, 7.11; N, 5.81.
Experimental values: C, 55.19; H, 7.34; N, 5.72.

参考例１０４で得た6-{4-メトキシ-3-[(メチルスルホニル)アミノ]フェニル}-6-オキソヘキシル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(1.00g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点142-144℃の無色結晶(802mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45(2H, m), 1.55-1.75(4H, m), 2.80-3.10(8H, m), 2.98(3H, s), 3.80(3H, s), 3.92(3H, s), 6.92(1H, t, J = 7.5Hz), 7.00(1H, d, J = 7.5Hz), 7.15-7.30(3H, m), 7.80-7.90(2H, m), 8.75-9.05(2H, br), 9.16(1H, s).
元素分析 C₂₃H₃₂N₂O₅S・HClとして
計算値：C, 56.95; H, 6.86; N, 5.78.
実験値：C, 56.61; H, 6.87; N, 5.69. N- [2-Methoxy-5- (6-{[2- (2-methoxyphenyl) ethyl] amino} hexanoyl) phenyl] methanesulfonamide hydrochloride

6- {4-Methoxy-3-[(methylsulfonyl) amino] phenyl} -6-oxohexyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl (1.00 g) obtained in Reference Example 104 was used. And the title compound was obtained as colorless crystals (802 mg) having a melting point of 142-144 ° C. by the same procedure as in Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.10 (8H, m), 2.98 (3H, s), 3.80 (3H, s), 3.92 (3H, s), 6.92 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 7.5Hz), 7.15-7.30 (3H, m), 7.80-7.90 (2H, m ), 8.75-9.05 (2H, br), 9.16 (1H, s).
Elemental analysis Calculated as C ₂₃ H ₃₂ N ₂ O ₅ S · HCl: C, 56.95; H, 6.86; N, 5.78.
Experimental value: C, 56.61; H, 6.87; N, 5.69.

参考例１０５で得た2-(2-クロロフェニル)エチル(6-{4-メトキシ-3-[(メチルスルホニル)アミノ]フェニル}-6-オキソヘキシル)カルバミン酸 tert-ブチル(1.26g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点112-115℃の無色結晶(941mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45(2H, m), 1.55-1.75(4H, m), 2.80-3.00(8H, m), 2.98(3H, s), 3.92(3H, s), 7.19(1H, d, J = 8.7Hz), 7.25-7.50(4H, m), 7.80-7.90(2H, m), 8.90-9.20(2H, br), 9.16(1H, s).
元素分析 C₂₂H₂₉ClN₂O₄S・HCl・0.5H₂Oとして
計算値：C, 53.01; H, 6.27; N, 5.62.
実験値：C, 52.96; H, 6.24; N, 5.64. N- [5- (6-{[2- (2-Chlorophenyl) ethyl] amino} hexanoyl) -2-methoxyphenyl] methanesulfonamide hydrochloride

Using tert-butyl 2- (2-chlorophenyl) ethyl (6- {4-methoxy-3-[(methylsulfonyl) amino] phenyl} -6-oxohexyl) carbamate obtained in Reference Example 105 (1.26 g) In the same manner as in Example 1, the title compound was obtained as colorless crystals (941 mg) having a melting point of 112-115 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.00 (8H, m), 2.98 (3H, s), 3.92 (3H, s), 7.19 (1H, d, J = 8.7Hz), 7.25-7.50 (4H, m), 7.80-7.90 (2H, m), 8.90-9.20 (2H, br), 9.16 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₂₉ ClN ₂ O ₄ S · HCl · 0.5H ₂ O: C, 53.01; H, 6.27; N, 5.62.
Experimental value: C, 52.96; H, 6.24; N, 5.64.

参考例１０６で得た5-(1H-インドール-3-イル)-5-オキソペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(1.00g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点171-173℃の無色結晶(391mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.65-1.80(4H, m), 2.85-3.20(8H, m), 7.10-7.40(7H, m), 7.48(1H, d, J = 7.2Hz), 8.20(1H, d, J = 7.5Hz), 8.36(1H, d, J = 3.2Hz), 8.80-9.15(2H, br), 12.12(1H, s). 1- (1H-Indol-3-yl) -5-[(2-phenylethyl) amino] -1-pentanone hydrochloride

The same operation as in Example 1 was carried out using tert-butyl 5- (1H-indol-3-yl) -5-oxopentyl (2-phenylethyl) carbamate (1.00 g) obtained in Reference Example 106. This gave the title compound as colorless crystals (391 mg) having a melting point of 171-173 ° C.
^{1 H NMR (200MHz, DMSO-} d 6) δ 1.65-1.80 (4H, m), 2.85-3.20 (8H, m), 7.10-7.40 (7H, m), 7.48 (1H, d, J = 7.2Hz) , 8.20 (1H, d, J = 7.5Hz), 8.36 (1H, d, J = 3.2Hz), 8.80-9.15 (2H, br), 12.12 (1H, s).

参考例１０７で得た5-(1H-インドール-3-イル)-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(901mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点143-145℃の無色結晶(672mg)として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.65-1.80(4H, m), 2.85-3.15(8H, m), 3.80(3H, s), 6.91(1H, t, J = 7.4Hz), 6.99(1H, d, J = 8.0Hz), 7.10-7.30(4H, m), 7.45-7.55(1H, m), 8.15-8.25(1H, m), 8.37(1H, d, J = 3.2Hz), 8.95-9.20(2H, br), 12.12(1H, s).
元素分析 C₂₂H₂₆N₂O₂・HCl・2.0H₂Oとして
計算値：C, 62.48; H, 7.39; N, 6.62.
実験値：C, 62.48; H, 6.95; N, 6.30. 1- (1H-Indol-3-yl) -5-{[2- (2-methoxyphenyl) ethyl] amino} -1-pentanone hydrochloride

Using tert-butyl 5- (1H-indol-3-yl) -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamate (901 mg) obtained in Reference Example 107, as in Example 1. The title compound was obtained as colorless crystals (672 mg) having a melting point of 143-145 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.65-1.80 (4H, m), 2.85-3.15 (8H, m), 3.80 (3H, s), 6.91 (1H, t, J = 7.4Hz), 6.99 (1H, d, J = 8.0Hz), 7.10-7.30 (4H, m), 7.45-7.55 (1H, m), 8.15-8.25 (1H, m), 8.37 (1H, d, J = 3.2Hz), 8.95-9.20 (2H, br), 12.12 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₂₆ N ₂ O ₂ · HCl · 2.0H ₂ O: C, 62.48; H, 7.39; N, 6.62.
Experimental value: C, 62.48; H, 6.95; N, 6.30.

参考例１０８で得た2-(2-クロロフェニル)エチル[5-(1H-インドール-3-イル)-5-オキソペンチル]カルバミン酸 tert-ブチル(1.00g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点149-151℃の無色結晶(925mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.65-1.85(4H, m), 2.80-3.20(8H, m), 7.05-7.50(7H, m), 8.20(1H, d, J = 6.3Hz), 8.37(1H, d, J = 3.0Hz), 9.05-9.30(2H, br), 12.12(1H, s).
元素分析 C₂₁H₂₃ClN₂O・HCl・3H₂Oとして
計算値：C, 56.63; H, 6.79; N, 6.29.
実験値：C, 56.41; H, 6.17; N, 6.04. 5-{[2- (2-Chlorophenyl) ethyl] amino} -1- (1H-indol-3-yl) -1-pentanone hydrochloride

Similar to Example 1 using tert-butyl 2- (2-chlorophenyl) ethyl [5- (1H-indol-3-yl) -5-oxopentyl] carbamate (1.00 g) obtained in Reference Example 108 The title compound was obtained as colorless crystals (925 mg) having a melting point of 149-151 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.65-1.85 (4H, m), 2.80-3.20 (8H, m), 7.05-7.50 (7H, m), 8.20 (1H, d, J = 6.3Hz) , 8.37 (1H, d, J = 3.0Hz), 9.05-9.30 (2H, br), 12.12 (1H, s).
Elemental analysis Calculated as C ₂₁ H ₂₃ ClN ₂ O · HCl · 3H ₂ O: C, 56.63; H, 6.79; N, 6.29.
Experimental value: C, 56.41; H, 6.17; N, 6.04.

参考例１０９で得た6-(1H-インドール-3-イル)-6-オキソヘキシル(2-フェニルエチル)カルバミン酸 tert-ブチル(838mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点160-162℃の無色結晶(650mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.50 (2H, m), 1.55-1.80 (4H, m), 2.80-3.20 (8H, m), 7.10-7.35 (7H, m), 7.47 (1H, d, J = 7.8Hz), 8.20 (1H, d, J = 6.9Hz), 8.35-8.40 (1H, m), 8.95-9.20 (2H, br), 12.05 (1H, s).
元素分析 C₂₂H₂₆N₂O・HClとして
計算値：C, 71.24; H, 7.34; N, 7.55.
実験値：C, 70.87; H, 7.45; N, 7.53. 1- (1H-Indol-3-yl) -6-[(2-phenylethyl) amino] -1-hexanone hydrochloride

The same procedure as in Example 1 is performed using tert-butyl 6- (1H-indol-3-yl) -6-oxohexyl (2-phenylethyl) carbamate (838 mg) obtained in Reference Example 109. Gave the title compound as colorless crystals (650 mg), mp 160-162 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.50 (2H, m), 1.55-1.80 (4H, m), 2.80-3.20 (8H, m), 7.10-7.35 (7H, m), 7.47 ( 1H, d, J = 7.8Hz), 8.20 (1H, d, J = 6.9Hz), 8.35-8.40 (1H, m), 8.95-9.20 (2H, br), 12.05 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₂₆ N ₂ O · HCl: C, 71.24; H, 7.34; N, 7.55.
Experimental value: C, 70.87; H, 7.45; N, 7.53.

参考例１１０で得た6-(1H-インドール-3-イル)-6-オキソヘキシル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(688mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点171-173℃の無色結晶(552mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.10 (8H, m), 3.80 (3H, s), 6.91 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 8.4Hz), 7.10-7.30 (4H, m), 7.47 (1H, d, J = 7.8Hz), 8.20 (1H, d, J = 6.9Hz), 8.35 (1H, d, J = 3.0Hz), 8.85-9.05 (2H, br), 12.04 (1H, s). 1- (1H-Indol-3-yl) -6-{[2- (2-methoxyphenyl) ethyl] amino} -1-hexanone hydrochloride

6- (1H-Indol-3-yl) -6-oxohexyl [2- (2-methoxyphenyl) ethyl] carbamate tert-butyl (688 mg) obtained in Reference Example 110 was used in the same manner as in Example 1. The title compound was obtained as colorless crystals (552 mg) having a melting point of 171-173 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.10 (8H, m), 3.80 (3H, s), 6.91 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 8.4Hz), 7.10-7.30 (4H, m), 7.47 (1H, d, J = 7.8Hz), 8.20 (1H, d, J = 6.9 Hz), 8.35 (1H, d, J = 3.0Hz), 8.85-9.05 (2H, br), 12.04 (1H, s).

参考例１１１で得た2-(2-クロロフェニル)エチル[6-(1H-インドール-3-イル)-6-オキソヘキシル]カルバミン酸 tert-ブチル(860mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点151-153℃の無色結晶(791mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45(2H, m), 1.55-1.80(4H, m), 2.80-3.20(8H, m), 7.15-7.50(7H, m), 8.20(1H, d, J = 6.9Hz), 8.36(1H, d, J = 3.0Hz), 9.10-9.30(2H, br), 12.04(1H, s).
元素分析 C₂₂H₂₅ClN₂O・HCl・2.5H₂Oとして
計算値：C, 58.67; H, 6.94; N, 6.22.
実験値：C, 58.04; H, 6.56; N, 6.01. 6-{[2- (2-Chlorophenyl) ethyl] amino} -1- (1H-indol-3-yl) -1-hexanone hydrochloride

Using tert-butyl 2- (2-chlorophenyl) ethyl [6- (1H-indol-3-yl) -6-oxohexyl] carbamate obtained in Reference Example 111 (860 mg), the same as in Example 1 By performing the operation, the title compound was obtained as colorless crystals (791 mg) having a melting point of 151-153 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.80 (4H, m), 2.80-3.20 (8H, m), 7.15-7.50 (7H, m), 8.20 ( 1H, d, J = 6.9Hz), 8.36 (1H, d, J = 3.0Hz), 9.10-9.30 (2H, br), 12.04 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₂₅ ClN ₂ O · HCl · 2.5H ₂ O: C, 58.67; H, 6.94; N, 6.22.
Experimental value: C, 58.04; H, 6.56; N, 6.01.

参考例１１２で得た5-オキソ-5-(2-チエニル)ペンチル(2-フェニルエチル)カルバミン酸 tert-ブチル(908mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点161-163℃の無色結晶(908mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.85-3.20 (8H, m), 7.20-7.40 (6H, m), 7.95-8.05 (2H, m), 9.10-9.35 (2H, br). 5-[(2-Phenylethyl) amino] -1- (2-thienyl) -1-pentanone hydrochloride

The title compound was obtained by the same procedures as in Example 1 using tert-butyl 5-oxo-5- (2-thienyl) pentyl (2-phenylethyl) carbamate (908 mg) obtained in Reference Example 112. Was obtained as colorless crystals (908 mg) having a melting point of 161-163 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.85-3.20 (8H, m), 7.20-7.40 (6H, m), 7.95-8.05 (2H, m), 9.10- 9.35 (2H, br).

参考例１１３で得た2-(2-メトキシフェニル)エチル[5-オキソ-5-(2-チエニル)ペンチル]カルバミン酸 tert-ブチル(1.45g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点101-103℃の無色結晶(1.04g)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80(4H, m), 2.85-3.10(8H, m), 3.80(3H, s), 6.91(1H, t, J = 7.2Hz), 7.00(1H, d, J = 8.1Hz), 7.18(1H, d, J = 7.2Hz), 7.20-7.30(2H, m), 7.95-8.05(2H, m), 8.95-9.15(2H, br).
元素分析 C₁₈H₂₃NO₂S・HClとして
計算値：C, 61.09; H, 6.84; N, 3.96.
実験値：C, 60.73; H, 6.62; N, 3.85. 5-{[2- (2-methoxyphenyl) ethyl] amino} -1- (2-thienyl) -1-pentanone hydrochloride

Using tert-butyl 2- (2-methoxyphenyl) ethyl [5-oxo-5- (2-thienyl) pentyl] carbamate (1.45 g) obtained in Reference Example 113, the same procedure as in Example 1 was performed. This gave the title compound as colorless crystals (1.04 g) with a melting point of 101-103 ° C.
^{1 H NMR (300MHz, DMSO-} d 6) δ 1.60-1.80 (4H, m), 2.85-3.10 (8H, m), 3.80 (3H, s), 6.91 (1H, t, J = 7.2Hz), 7.00 (1H, d, J = 8.1Hz), 7.18 (1H, d, J = 7.2Hz), 7.20-7.30 (2H, m), 7.95-8.05 (2H, m), 8.95-9.15 (2H, br).
Elemental analysis Calculated as C ₁₈ H ₂₃ NO ₂ S · HCl: C, 61.09; H, 6.84; N, 3.96.
Experimental values: C, 60.73; H, 6.62; N, 3.85.

参考例１１４で得た2-(2-クロロフェニル)エチル[5-オキソ-5-(2-チエニル)ペンチル]カルバミン酸 tert-ブチル(1.47g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点146-147℃の無色結晶(1.09g)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-1.80(4H, m), 2.85-3.20(8H, m), 7.20-7.50(5H, m), 7.95-8.05(2H, m), 9.05-9.30(2H, br).
元素分析 C₁₇H₂₀ClNOS・HClとして
計算値：C, 56.98; H, 5.91; N, 3.91.
実験値：C, 56.76; H, 5.82; N, 3.96. 5-{[2- (2-Chlorophenyl) ethyl] amino} -1- (2-thienyl) -1-pentanone hydrochloride

Using tert-butyl 2- (2-chlorophenyl) ethyl [5-oxo-5- (2-thienyl) pentyl] carbamate obtained in Reference Example 114 (1.47 g), the same operation as in Example 1 was performed. This gave the title compound as colorless crystals (1.09 g) with a melting point of 146-147 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.85-3.20 (8H, m), 7.20-7.50 (5H, m), 7.95-8.05 (2H, m), 9.05- 9.30 (2H, br).
Elemental analysis Calculated as C ₁₇ H ₂₀ ClNOS · HCl: C, 56.98; H, 5.91; N, 3.91.
Experimental value: C, 56.76; H, 5.82; N, 3.96.

参考例１１５で得た6-オキソ-6-(2-チエニル)ヘキシル(2-フェニルエチル)カルバミン酸 tert-ブチル(863mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点152-154℃の無色結晶(685mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45(2H, m), 1.55-1.80(4H, m), 2.80-3.20(8H, m), 7.20-7.40(6H, m), 7.95-8.05(2H, m), 9.00-9.20(2H, br). 6-[(2-Phenylethyl) amino] -1- (2-thienyl) -1-hexanone hydrochloride

The title compound was obtained by the same procedures as in Example 1 using tert-butyl 6-oxo-6- (2-thienyl) hexyl (2-phenylethyl) carbamate (863 mg) obtained in Reference Example 115. Was obtained as colorless crystals (685 mg) having a melting point of 152-154 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.80 (4H, m), 2.80-3.20 (8H, m), 7.20-7.40 (6H, m), 7.95- 8.05 (2H, m), 9.00-9.20 (2H, br).

参考例１１６で得た2-(2-メトキシフェニル)エチル[6-オキソ-6-(2-チエニル)ヘキシル]カルバミン酸 tert-ブチル(884mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点107-109℃の無色結晶(643mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45(2H, m), 1.55-1.75(4H, m), 2.80-3.10(8H, m), 3.80(3H, s), 6.92(1H, t, J = 7.5Hz), 7.00(1H, d, J = 8.4Hz), 7.18(1H, d, J = 6.9Hz), 7.20-7.30(2H, m), 7.95-8.05(2H, m), 8.80-9.10(2H, br).
元素分析 C₁₉H₂₅NO₂S・HClとして
計算値：C, 62.02; H, 7.12; N, 3.81.
実験値：C, 61.80; H, 7.04; N, 3.88. 6-{[2- (2-methoxyphenyl) ethyl] amino} -1- (2-thienyl) -1-hexanone hydrochloride

The same operation as in Example 1 was carried out using tert-butyl 2- (2-methoxyphenyl) ethyl [6-oxo-6- (2-thienyl) hexyl] carbamate (884 mg) obtained in Reference Example 116. This gave the title compound as colorless crystals (643 mg) with a melting point of 107-109 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.10 (8H, m), 3.80 (3H, s), 6.92 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 8.4Hz), 7.18 (1H, d, J = 6.9Hz), 7.20-7.30 (2H, m), 7.95-8.05 (2H, m), 8.80-9.10 (2H, br).
Elemental analysis Calculated as C ₁₉ H ₂₅ NO ₂ S · HCl: C, 62.02; H, 7.12; N, 3.81.
Experimental value: C, 61.80; H, 7.04; N, 3.88.

参考例１１７で得た2-(2-クロロフェニル)エチル[6-オキソ-6-(2-チエニル)ヘキシル]カルバミン酸 tert-ブチル(1.07g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点149-151℃の無色結晶(849mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45(2H, m), 1.55-1.75(4H, m), 2.80-3.20(8H, m), 7.20-7.50(5H, m), 7.95-8.05(2H, m), 9.00-9.35(2H, br).
元素分析 C₁₈H₂₂ClNOS・HCl・H₂Oとして
計算値：C, 55.38; H, 6.46; N, 3.59.
実験値：C, 55.20; H, 6.57; N, 3.67. 6-{[2- (2-Chlorophenyl) ethyl] amino} -1- (2-thienyl) -1-hexanone hydrochloride

Using tert-butyl 2- (2-chlorophenyl) ethyl [6-oxo-6- (2-thienyl) hexyl] carbamate (1.07 g) obtained in Reference Example 117, the same procedure as in Example 1 was performed. This gave the title compound as colorless crystals (849 mg) with a melting point of 149-151 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.20 (8H, m), 7.20-7.50 (5H, m), 7.95- 8.05 (2H, m), 9.00-9.35 (2H, br).
Elemental analysis Calculated as C ₁₈ H ₂₂ ClNOS · HCl · H ₂ O: C, 55.38; H, 6.46; N, 3.59.
Experimental values: C, 55.20; H, 6.57; N, 3.67.

参考例１１８で得た(±)-5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル(1,2,3,4-テトラヒドロ-1-ナフタレニル)カルバミン酸 tert-ブチル(520mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(420mg) を淡黄色非晶状粉末として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.60-2.25(8H, m), 2.59(2H, t, J = 7.6Hz), 2.65-3.05(8H, m), 3.17(2H, t, J = 8.4Hz), 3.60-3.70(1H, m), 3.98(2H, t, J = 8.4Hz), 7.15-7.35(3H, m), 7.65-7.80(3H, m), 9.05-9.35(2H, br). (±) -8- [5- (1,2,3,4-Tetrahydro-1-naphthalenylamino) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-4-one hydrochloride

(±) -5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl obtained in Reference Example 118 The title compound (420 mg) was obtained as a pale yellow amorphous product by carrying out the same operation as in Example 1 using tert-butyl (1,2,3,4-tetrahydro-1-naphthalenyl) carbamate (520 mg). Obtained as a powder.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.60-2.25 (8H, m), 2.59 (2H, t, J = 7.6Hz), 2.65-3.05 (8H, m), 3.17 (2H, t, J = 8.4Hz), 3.60-3.70 (1H, m), 3.98 (2H, t, J = 8.4Hz), 7.15-7.35 (3H, m), 7.65-7.80 (3H, m), 9.05-9.35 (2H, br ).

参考例１１９で得た(±)-1,2-ジフェニルエチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(837mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点210-212℃の無色結晶(472mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.45-1.80(4H, m), 2.50-2.65(3H, m), 2.75-3.05(5H, m), 3.10-3.25(3H, m), 3.55-3.70(1H, m), 3.99(2H, t, J = 8.4Hz), 4.40-4.55(1H, m), 6.95-7.05(2H, m), 7.10-7.20(3H, m), 7.30-7.40(3H, m), 7.40-7.50(2H, m), 7.70-7.80(2H, m), 9.45-9.60(1H, br), 9.85-10.05(1H, br). (±) -8- {5-[(1,2-Diphenylethyl) amino] pentanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

(±) -1,2-Diphenylethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] obtained in Reference Example 119 The title compound was obtained as colorless crystals (472 mg) having a melting point of 210-212 ° C. by performing the same procedure as in Example 1 using tert-butyl (quinolin-8-yl) pentyl] carbamate (837 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.45-1.80 (4H, m), 2.50-2.65 (3H, m), 2.75-3.05 (5H, m), 3.10-3.25 (3H, m), 3.55- 3.70 (1H, m), 3.99 (2H, t, J = 8.4Hz), 4.40-4.55 (1H, m), 6.95-7.05 (2H, m), 7.10-7.20 (3H, m), 7.30-7.40 ( 3H, m), 7.40-7.50 (2H, m), 7.70-7.80 (2H, m), 9.45-9.60 (1H, br), 9.85-10.05 (1H, br).

参考例1で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびN-ベンジル-N-[2-(2-メトキシフェニル)エチル]アミン(455mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(353mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.50-1.90(6H, m), 2.55(2H, t, J = 6.8Hz), 2.60-3.30(10H, m), 3.65(2H, s), 3.74(3H, s), 4.10(2H, t, J = 8.8Hz), 6.75-6.90(2H, m), 7.05-7.35(7H, m), 7.64(1H, s), 7.68(1H, s). 8- (5- {Benzyl [2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and N-benzyl obtained in Reference Example 1 The same operation as in Example 9 was performed using -N- [2- (2-methoxyphenyl) ethyl] amine (455 mg) to give the title compound (353 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.50-1.90 (6H, m), 2.55 (2H, t, J = 6.8 Hz), 2.60-3.30 (10H, m), 3.65 (2H, s), 3.74 (3H, s), 4.10 (2H, t, J = 8.8Hz), 6.75-6.90 (2H, m), 7.05-7.35 (7H, m), 7.64 (1H, s), 7.68 (1H, s) .

参考例７８で得たtrans-8-{[4-(アミノメチル)シクロヘキシル]カルボニル}-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン 塩酸塩(1.00g) および炭酸カリウム(1.00g) のジメチルホルムアミド(3ml) 懸濁液に、(2-ブロモエチル)ベンゼン(471mg) を室温にて滴下した。120℃で３０分攪拌後、反応液に水(30ml)および酢酸エチル(30ml)を加え、酢酸エチルで抽出した。抽出液を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル−メタノール(9:1))にて精製し、表題化合物のフリー塩基体を無色油状物(500mg)として得た。さらに塩化水素-酢酸エチル溶液で処理することにより、表題化合物を融点252-254℃の無色結晶(474mg)として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 0.95-1.20 (2H, m), 1.35-1.70 (5H, m), 1.75-2.05 (4H, m), 2.51 (2H, d, J = 6.3Hz), 2.70 (2H, t, J = 7.8Hz), 2.75-2.90 (3H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.15 (1H, m), 3.22 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.10-7.35 (5H, m), 7.64 (1H, s), 7.68 (1H, s).
元素分析 C₂₇H₃₂ClN₂O₂・HClとして
計算値：C, 70.19; H, 7.42; N, 6.06.
実験値：C, 70.58; H, 7.35; N, 5.81. trans-8-[(4-{[(2-phenylethyl) amino] methyl} cyclohexyl) carbonyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

Trans-8-{[4- (Aminomethyl) cyclohexyl] carbonyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one obtained in Reference Example 78 (2-Bromoethyl) benzene (471 mg) was added dropwise at room temperature to a suspension of hydrochloride (1.00 g) and potassium carbonate (1.00 g) in dimethylformamide (3 ml). After stirring at 120 ° C. for 30 minutes, water (30 ml) and ethyl acetate (30 ml) were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; ethyl acetate-methanol (9: 1)) to obtain the free base of the title compound as a colorless oil (500 mg). Further treatment with a hydrogen chloride-ethyl acetate solution gave the title compound as colorless crystals (474 mg) having a melting point of 252-254 ° C.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 0.95-1.20 (2H, m), 1.35-1.70 (5H, m), 1.75-2.05 (4H, m), 2.51 (2H, d, J = 6.3 Hz ), 2.70 (2H, t, J = 7.8Hz), 2.75-2.90 (3H, m), 3.01 (2H, t, J = 7.8Hz), 3.05-3.15 (1H, m), 3.22 (2H, t, J = 8.4Hz), 4.12 (2H, t, J = 8.4Hz), 7.10-7.35 (5H, m), 7.64 (1H, s), 7.68 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₂ ClN ₂ O ₂ .HCl: C, 70.19; H, 7.42; N, 6.06.
Experimental value: C, 70.58; H, 7.35; N, 5.81.

参考例７８で得たtrans-8-{[4-(アミノメチル)シクロヘキシル]カルボニル}-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン 塩酸塩(758mg) およびメタンスルホン酸2-(2-クロロフェニル)エチル(510mg) を用いて、実施例１９６と同様の操作を行うことにより、表題化合物を融点271-273℃の無色結晶(454mg)として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 0.95-1.20 (2H, m), 1.35-1.70 (5H, m), 1.75-2.05 (4H, m), 2.55 (2H, d, J = 6.3Hz), 2.71 (2H, t, J = 7.8Hz), 2.80-2.95 (3H, m), 3.02 (2H, t, J = 7.8Hz), 3.05-3.20 (1H, m), 3.23 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.10-7.40 (4H, m), 7.65 (1H, s), 7.69 (1H, s).
元素分析 C₂₇H₃₁N₂O₂Cl・HCl・0.5H₂Oとして
計算値：C, 65.32; H, 6.70; N, 5.64.
実験値：C, 65.70; H, 6.52; N, 5.54. trans-8-{[4-({[2- (2-chlorophenyl) ethyl] amino} methyl) cyclohexyl] carbonyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij ] Quinolin-4-one hydrochloride

Trans-8-{[4- (Aminomethyl) cyclohexyl] carbonyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one obtained in Reference Example 78 The title compound was purified in the same manner as in Example 196 using hydrochloride (758 mg) and 2- (2-chlorophenyl) ethyl methanesulfonate (510 mg) to give the title compound as colorless crystals (454 mg) having a melting point of 271-273 ° C. Got as.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 0.95-1.20 (2H, m), 1.35-1.70 (5H, m), 1.75-2.05 (4H, m), 2.55 (2H, d, J = 6.3 Hz ), 2.71 (2H, t, J = 7.8Hz), 2.80-2.95 (3H, m), 3.02 (2H, t, J = 7.8Hz), 3.05-3.20 (1H, m), 3.23 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.10-7.40 (4H, m), 7.65 (1H, s), 7.69 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₁ N ₂ O ₂ Cl · HCl · 0.5H ₂ O: C, 65.32; H, 6.70; N, 5.64.
Experimental value: C, 65.70; H, 6.52; N, 5.54.

参考例１２２で得た1-(3-アセチル-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン7-イル)-5-クロロ-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点117-119℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.68 (4H, m), 2.08 (3H, s), 2.91 (4H, m), 3.05 (8H, m), 3.56 (4H, m), 7.33-7.46 (5H, m), 7.77 (2H, m), 9.18 (2H, br). 1- (3-Acetyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -5-{[2- (2-chlorophenyl) ethyl] amino} -1-pentanone hydrochloride

1- (3-acetyl-2,3,4,5-tetrahydro-1H-3-benzazepine 7-yl) -5-chloro-1-pentanone and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 122 were used. The title compound was obtained as colorless crystals having a melting point of 117-119 ° C. by sequentially performing the same operations as in Reference Example 19 and Example 1.
^{1 H NMR (300MHz, DMSO-} d 6) δ 1.68 (4H, m), 2.08 (3H, s), 2.91 (4H, m), 3.05 (8H, m), 3.56 (4H, m), 7.33-7.46 (5H, m), 7.77 (2H, m), 9.18 (2H, br).

参考例１２２で得た1-(3-アセチル-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル)-5-クロロ-1-ペンタノンおよび2-(2-メトキシフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点93-94℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.67 (4H, m), 2.08 (3H, s), 2.93 (4H, m), 3.04 (8H, m), 3.58 (4H, m), 3.80 (3H, s), 6.88-7.02 (2H, m), 7.17-7.33 (3H, m), 7.75 (2H, m), 8.83 (2H, br). 1- (3-Acetyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -5-{[2- (2-methoxyphenyl) ethyl] amino} -1-pentanone hydrochloride

1- (3-acetyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -5-chloro-1-pentanone and 2- (2-methoxyphenyl) obtained in Reference Example 122 The title compound was obtained as colorless crystals having a melting point of 93-94 ° C. by sequentially performing the same operations as in Reference Example 19 and Example 1 using ethylamine.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.67 (4H, m), 2.08 (3H, s), 2.93 (4H, m), 3.04 (8H, m), 3.58 (4H, m), 3.80 (3H , s), 6.88-7.02 (2H, m), 7.17-7.33 (3H, m), 7.75 (2H, m), 8.83 (2H, br).

参考例１２３で得た5-クロロ-1-[3-(メチルスルホニル)-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル]-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点162-164℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.69 (4H, m), 2.88 (3H, s), 3.10 (8H, m), 3.36 (8H, m), 7.33-7.46 (5H, m), 7.78 (2H, m), 8.99 (2H, br). 5-{[2- (2-Chlorophenyl) ethyl] amino} -1- [3- (methylsulfonyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone Hydrochloride

5-chloro-1- [3- (methylsulfonyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone and 2- (2- The title compound was obtained as colorless crystals having a melting point of 162-164 ° C. by sequentially performing the same operations as in Reference Example 19 and Example 1 using chlorophenyl) ethylamine.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.69 (4H, m), 2.88 (3H, s), 3.10 (8H, m), 3.36 (8H, m), 7.33-7.46 (5H, m), 7.78 (2H, m), 8.99 (2H, br).

参考例６６で得た5-(5-クロロペンタノイル)-2-メトキシベンゼンスルホンアミドおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.67 (4H, m), 2.88 (3H, s), 2.96-3.07 (10H, m), 3.36 (6H, m), 3.80 (3H, s), 6.88-7.23 (2H, m), 7.17-7.36 (3H, m), 7.78 (2H, m), 8.88 (2H, br). 5-{[2- (2-methoxyphenyl) ethyl] amino} -1- [3- (methylsulfonyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1- Pentanone hydrochloride

Reference Example 19 and Example were obtained using 5- (5-chloropentanoyl) -2-methoxybenzenesulfonamide and N- [2- (2-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 66. The title compound was obtained as a pale yellow amorphous powder by sequentially performing the same operations as in 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.67 (4H, m), 2.88 (3H, s), 2.96-3.07 (10H, m), 3.36 (6H, m), 3.80 (3H, s), 6.88 -7.23 (2H, m), 7.17-7.36 (3H, m), 7.78 (2H, m), 8.88 (2H, br).

参考例１２４で得た7-(5-クロロペンタノイル)-N-エチル-1,2,4,5-テトラヒドロ-3H-3-ベンズアゼピン-3-カルボキサミドおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点149-150℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.02 (3H, t, J = 7.0Hz), 1.69 (4H, m), 2.91 (4H, m), 3.08 (10H, m), 3.49 (4H, m), 7.28-7.50 (5H, m), 7.75 (2H, m), 8.23 (1H, m), 9.11 (2H, br). 7- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -N-ethyl-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxamide hydrochloride

Using 7- (5-chloropentanoyl) -N-ethyl-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxamide and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 124 The title compound was obtained as colorless crystals having a melting point of 149-150 ° C. by sequentially performing the same operations as in Reference Example 19 and Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.02 (3H, t, J = 7.0Hz), 1.69 (4H, m), 2.91 (4H, m), 3.08 (10H, m), 3.49 (4H, m ), 7.28-7.50 (5H, m), 7.75 (2H, m), 8.23 (1H, m), 9.11 (2H, br).

参考例１２４で得た7-(5-クロロペンタノイル)-N-エチル-1,2,4,5-テトラヒドロ-3H-3-ベンズアゼピン-3-カルボキサミドおよび2-(2-メトキシフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点150-151℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.02 (3H, t, J = 7.0Hz), 1.68 (4H, m), 2.90 (4H, m), 3.07 (10H, m), 3.47 (4H, m), 3.80 (3H, s), 6.88-7.02 (2H, m), 7.17-7.31 (3H, m), 7.73 (2H, m), 8.23 (1H, m), 9.01 (2H, br). N-ethyl-7- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxamide hydrochloride

7- (5-Chloropentanoyl) -N-ethyl-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxamide and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 124 were used. The title compound was obtained as colorless crystals having a melting point of 150-151 ° C. by sequentially performing the same operations as in Reference Example 19 and Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.02 (3H, t, J = 7.0Hz), 1.68 (4H, m), 2.90 (4H, m), 3.07 (10H, m), 3.47 (4H, m ), 3.80 (3H, s), 6.88-7.02 (2H, m), 7.17-7.31 (3H, m), 7.73 (2H, m), 8.23 (1H, m), 9.01 (2H, br).

参考例１２０で得た5-クロロ-1-[3-(トリフルオロアセチル)-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル]-1-ペンタノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.80 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.4Hz), 2.57-2.62 (2H, m), 2.86-3.07 (8H, m), 3.69-3.81 (4H, m), 7.11-7.34 (5H, m), 7.75-7.78 (2H, m). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone hydrochloride

5-chloro-1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone and N- [2 obtained in Reference Example 120 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using-(2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.80 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.57-2.62 (2H, m), 2.86-3.07 (8H, m), 3.69-3.81 (4H, m), 7.11-7.34 (5H, m), 7.75-7.78 (2H, m).

参考例２０４で得た5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]-1-[3-(トリフルオロアセチル)-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル]-1-ペンタノン (1.50g)のメタノール(40ml)−水(40ml) 溶液に、炭酸カリウム(3.2g, 23.5mmol) を加えた。室温で６０分攪拌後、溶媒を減圧下留去し、水(100g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去することにより表題化合物のフリー塩基体を淡黄色油状物(1.2g) として得た。上記フリー塩基体のエタノール溶液を塩化水素(酢酸エチル溶液)で処理し、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.79 (4H, m), 2.33 (3H, s), 2.45 (2H, t, J = 7.4Hz), 2.57-2.62 (2H, m), 2.86-2.97 (13H, m), 7.10-7.34 (5H, m), 7.68-7.71 (2H, m). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -1-pentanone dihydrochloride

5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3- obtained in Reference Example 204 To a solution of benzazepin-7-yl] -1-pentanone (1.50 g) in methanol (40 ml) -water (40 ml), potassium carbonate (3.2 g, 23.5 mmol) was added. After stirring at room temperature for 60 minutes, the solvent was distilled off under reduced pressure, water (100 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure to give the free base of the title compound as a pale yellow oil (1.2 g). The ethanol solution of the free base was treated with hydrogen chloride (ethyl acetate solution) to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.79 (4H, m), 2.33 (3H, s), 2.45 (2H, t, J = 7.4 Hz), 2.57-2.62 (2H, m), 2.86-2.97 (13H, m), 7.10-7.34 (5H, m), 7.68-7.71 (2H, m).

実施例２０５で得た5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル)-1-ペンタノン(294mg)およびトリエチルアミン(139μｌ)のテトラヒドロフラン(2ml)溶液に、アセチルクロリド(54μl)を加えた。室温で６０分攪拌後、水(10g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去し、次いでシリカゲルカラムクロマトグラフィーにて精製することにより、表題化合物のフリー塩基体を淡黄色油状物(280mg) として得た。上記フリー塩基体のエタノール溶液を塩化水素(酢酸エチル溶液)で処理し、表題化合物を淡黄色非晶状粉末(220mg)として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.80 (4H, m), 2.19 (3H, s), 2.36 (3H, s), 2.45 (2H, t, J = 7.4Hz), 2.60-2.68 (2H, m), 2.88-3.00 (8H, m), 3.58-3.86 (4H, m), 7.12-7.34 (5H, m), 7.73-7.76 (2H, m). 1- (3-acetyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] -1-pentanone Hydrochloride

5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -1 obtained in Example 205 -Acetyl chloride (54 μl) was added to a solution of pentanone (294 mg) and triethylamine (139 μl) in tetrahydrofuran (2 ml). After stirring at room temperature for 60 minutes, water (10 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. The organic layer was dried over sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the free base of the title compound as a pale yellow oil (280 mg). The ethanol solution of the free base was treated with hydrogen chloride (ethyl acetate solution) to obtain the title compound as a pale yellow amorphous powder (220 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.80 (4H, m), 2.19 (3H, s), 2.36 (3H, s), 2.45 (2H, t, J = 7.4Hz), 2.60- 2.68 (2H, m), 2.88-3.00 (8H, m), 3.58-3.86 (4H, m), 7.12-7.34 (5H, m), 7.73-7.76 (2H, m).

実施例２０５で得た5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル)-1-ペンタノン(223mg)およびトリエチルアミン(139μｌ)のテトラヒドロフラン(2ml)溶液に、メチルスルホニルクロリド(45μl)を加えた。室温で６０分攪拌後、水(10g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去し、次いでシリカゲルカラムクロマトグラフィーにて精製することにより、表題化合物のフリー塩基体を淡黄色油状物(230mg) として得た。上記フリー塩基体のエタノール溶液を塩化水素(酢酸エチル溶液)で処理し、表題化合物を淡黄色非晶状粉末(200mg)として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.79 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.4Hz), 2.57-2.65 (2H, m), 2.79 (3H, s), 2.86-2.99 (4H, m), 3.08-3.11 (4H, m), 3.43-3.49 (4H, m), 7.11-7.34 (5H, m), 7.74-7.77 (2H, m). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- [3- (methylsulfonyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]- 1-Pentanone hydrochloride

5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -1 obtained in Example 205 -To a solution of pentanone (223 mg) and triethylamine (139 μl) in tetrahydrofuran (2 ml) was added methylsulfonyl chloride (45 μl). After stirring at room temperature for 60 minutes, water (10 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. The organic layer was dried over sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the free base of the title compound as a pale yellow oil (230 mg). The ethanol solution of the above free base was treated with hydrogen chloride (ethyl acetate solution) to obtain the title compound as a pale yellow amorphous powder (200 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.79 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.57-2.65 (2H, m), 2.79 (3H, s), 2.86-2.99 (4H, m), 3.08-3.11 (4H, m), 3.43-3.49 (4H, m), 7.11-7.34 (5H, m), 7.74-7.77 (2H, m ).

実施例２０５で得た5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル)-1-ペンタノン(365mg)のテトラヒドロフラン(2ml)溶液に、イソシアン酸エチル(74μl)を加えた。室温で６０分攪拌後、水(10g) を加え、次いで酢酸エチルで抽出、飽和食塩水で洗浄した。有機層を硫酸ナトリウムで乾燥した後、溶媒を減圧下留去し、ついでシリカゲルカラムクロマトグラフィーにて精製することにより、表題化合物のフリー塩基体を淡黄色油状物(330mg) として得た。上記フリー塩基体のエタノール溶液を塩化水素(酢酸エチル溶液)で処理し、表題化合物を淡黄色非晶状粉末(290mg)として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.16 (3H, t, J = 7.2Hz), 1.58-1.77 (4H, m), 2.38 (3H, s), 2.54 (2H, t, J = 7.4Hz), 2.63-2.69 (2H, m), 2.90-3.00 (8H, m), 3.31 (2H, q, J = 7.2Hz), 3.54-3.59 (4H, m), 4.74 (1H, m), 7.11-7.32 (5H, m), 7.69-7.72 (2H, m). 7- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -N-ethyl-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxamide hydrochloride

5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -1 obtained in Example 205 -To a solution of pentanone (365 mg) in tetrahydrofuran (2 ml) was added ethyl isocyanate (74 μl). After stirring at room temperature for 60 minutes, water (10 g) was added, followed by extraction with ethyl acetate and washing with saturated brine. The organic layer was dried over sodium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to obtain the free base of the title compound as a pale yellow oil (330 mg). The ethanol solution of the above free base was treated with hydrogen chloride (ethyl acetate solution) to obtain the title compound as a pale yellow amorphous powder (290 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.16 (3H, t, J = 7.2 Hz), 1.58-1.77 (4H, m), 2.38 (3H, s), 2.54 (2H, t, J = 7.4 Hz), 2.63-2.69 (2H, m), 2.90-3.00 (8H, m), 3.31 (2H, q, J = 7.2Hz), 3.54-3.59 (4H, m), 4.74 (1H, m), 7.11 -7.32 (5H, m), 7.69-7.72 (2H, m).

参考例１２０で得た5-クロロ-1-[3-(トリフルオロアセチル)-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル]-1-ペンタノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.80 (4H, m), 2.33 (3H, s), 2.48 (2H, t, J = 7.4Hz), 2.57-2.62 (2H, m), 2.76-2.80 (2H, m), 2.93-3.06 (6H, m), 3.68-3.81 (4H, m), 3.81 (3H, s), 6.86 (2H, t, J = 9.2Hz), 7.12-7.27 (3H, m), 7.75-7.78 (2H, m). 5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl ] -1-Pentanone

5-chloro-1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone and N- [2 obtained in Reference Example 120 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using-(2-methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.80 (4H, m), 2.33 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.57-2.62 (2H, m), 2.76-2.80 (2H, m), 2.93-3.06 (6H, m), 3.68-3.81 (4H, m), 3.81 (3H, s), 6.86 (2H, t, J = 9.2Hz), 7.12-7.27 ( 3H, m), 7.75-7.78 (2H, m).

実施例２０９で得た5-[[2-(2-メトキシフェニル)エチル](メチル)アミノ]-1-[3-(トリフルオロアセチル)-2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル]-1-ペンタノンを用いて、実施例２０５と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.57-1.79 (4H, m), 2.31 (3H, s), 2.45 (2H, t, J = 7.4Hz), 2.53-2.60 (2H, m), 2.74-2.82 (2H, m), 2.91-2.96 (11H, m), 3.81 (3H, s), 6.81-6.90 (2H, m), 7.12-7.20 (3H, m), 7.68-7.72 (2H, m). 5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -1-pentanone dihydrochloride

5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- [3- (trifluoroacetyl) -2,3,4,5-tetrahydro-1H-3 obtained in Example 209 -Benzazepin-7-yl] -1-pentanone was used in the same manner as in Example 205 to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.57-1.79 (4H, m), 2.31 (3H, s), 2.45 (2H, t, J = 7.4 Hz), 2.53-2.60 (2H, m), 2.74-2.82 (2H, m), 2.91-2.96 (11H, m), 3.81 (3H, s), 6.81-6.90 (2H, m), 7.12-7.20 (3H, m), 7.68-7.72 (2H, m ).

実施例２１０で得た5-[[2-(2-メトキシフェニル)エチル](メチル)アミノ]-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル)-1-ペンタノンを用いて、実施例２０６と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.80 (4H, m), 2.19 (3H, s), 2.35 (3H, s), 2.51 (2H, t, J = 7.4Hz), 2.58-2.65 (2H, m), 2.77-2.85 (2H, m), 2.93-3.00 (6H, m), 3.57-3.76 (4H, m), 3.81 (3H, s), 6.82-6.91 (2H, m), 7.12-7.25 (3H, m), 7.73 (2H, m). 1- (3-acetyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl) -5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] -1- Pentanone hydrochloride

5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-obtained in Example 210 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 206 using 1-pentanone.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.80 (4H, m), 2.19 (3H, s), 2.35 (3H, s), 2.51 (2H, t, J = 7.4Hz), 2.58- 2.65 (2H, m), 2.77-2.85 (2H, m), 2.93-3.00 (6H, m), 3.57-3.76 (4H, m), 3.81 (3H, s), 6.82-6.91 (2H, m), 7.12-7.25 (3H, m), 7.73 (2H, m).

実施例２１０で得た5-[[2-(2-メトキシフェニル)エチル](メチル)アミノ]-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル)-1-ペンタノンを用いて、実施例２０７と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.56-1.80 (4H, m), 2.36 (3H, s), 2.52 (2H, t, J = 7.4Hz), 2.58-2.69 (2H, m), 2.78 (3H, s), 2.75-2.85 (2H, m), 3.06-3.12 (4H, m), 3.43-3.47 (4H, m), 3.81 (3H, s), 6.82-6.91 (2H, m), 7.11-7.27 (3H, m), 7.73 (2H, m). 5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- [3- (methylsulfonyl) -2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl] -1-pentanone hydrochloride

5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-obtained in Example 210 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 207 using 1-pentanone.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.56-1.80 (4H, m), 2.36 (3H, s), 2.52 (2H, t, J = 7.4 Hz), 2.58-2.69 (2H, m), 2.78 (3H, s), 2.75-2.85 (2H, m), 3.06-3.12 (4H, m), 3.43-3.47 (4H, m), 3.81 (3H, s), 6.82-6.91 (2H, m), 7.11-7.27 (3H, m), 7.73 (2H, m).

実施例２１０で得た5-[[2-(2-メトキシフェニル)エチル](メチル)アミノ]-1-(2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン-7-イル)-1-ペンタノンを用いて、実施例２０８と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.17 (3H, t, J = 7.4Hz), 1.56-1.79 (4H, m), 2.36 (3H, s), 2.52 (2H, t, J = 7.4Hz), 2.58-2.69 (2H, m), 2.75-2.84 (2H, m), 2.93-3.00 (6H, m), 3.32 (2H, q, J = 7.2Hz), 3.53-3.58 (4H, m), 3.81 (3H, s), 4.70 (1H, m), 6.81-6.90 (2H, m), 7.12-7.21 (3H, m), 7.71 (2H, m). N-ethyl-7- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxamide hydrochloride

5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- (2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-obtained in Example 210 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 208 using 1-pentanone.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.17 (3H, t, J = 7.4 Hz), 1.56-1.79 (4H, m), 2.36 (3H, s), 2.52 (2H, t, J = 7.4 Hz), 2.58-2.69 (2H, m), 2.75-2.84 (2H, m), 2.93-3.00 (6H, m), 3.32 (2H, q, J = 7.2Hz), 3.53-3.58 (4H, m) , 3.81 (3H, s), 4.70 (1H, m), 6.81-6.90 (2H, m), 7.12-7.21 (3H, m), 7.71 (2H, m).

参考例１２５で得た1-(2-アセチル-1,2,3,4-テトラヒドロ-7-イソキノリニル)-5-クロロ-1-ペンタノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.79 (4H, m), 2.19 (3H, s), 2.34 (3H, s), 2.48 (2H, t, J = 7.0Hz), 2.57-2.65 (2H, m), 2.87-2.98 (6H, m), 3.69 (2H, t, J = 5.8Hz), 4.67 (2H, s), 7.11-7.34 (5H, m), 8.83 (1H, s), 7.74-7.80 (2H, m). 1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] -1-pentanone hydrochloride

1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-chloro-1-pentanone and N- [2- (2-chlorophenyl) ethyl] -N obtained in Reference Example 125 The title compound was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.79 (4H, m), 2.19 (3H, s), 2.34 (3H, s), 2.48 (2H, t, J = 7.0 Hz), 2.57- 2.65 (2H, m), 2.87-2.98 (6H, m), 3.69 (2H, t, J = 5.8Hz), 4.67 (2H, s), 7.11-7.34 (5H, m), 8.83 (1H, s) , 7.74-7.80 (2H, m).

実施例２１４で得た1-(2-アセチル-1,2,3,4-テトラヒドロ-7-イソキノリニル)-5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]-1-ペンタノン(5.0g)の濃塩酸(150ml) 溶液を１３０℃で２時間攪拌後、反応溶液の溶媒を減圧下留去することにより表題化合物の粗成績体を淡黄色固形物(4.2g) として得た。さらにエタノール−ジエチルエーテルからの再結晶により、表題化合物を融点95℃(分解)の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.60-1.79 (4H, m), 2.21 (1H, br), 2.37 (3H, s), 2.52 (2H, t, J = 7.4Hz), 2.65 (2H, m), 2.88-3.26 (6H, m), 3.58 (2H, t, J = 5.8Hz), 4.10 (2H, s), 7.12-7.35 (5H, m), 7.71-7.81 (2H, m). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (1,2,3,4-tetrahydro-7-isoquinolinyl) -1-pentanone dihydrochloride

1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] -1-pentanone obtained in Example 214 After stirring a solution of (5.0 g) in concentrated hydrochloric acid (150 ml) at 130 ° C. for 2 hours, the solvent of the reaction solution was distilled off under reduced pressure to obtain a crude product of the title compound as a pale yellow solid (4.2 g). . Further, recrystallization from ethanol-diethyl ether gave the title compound as colorless crystals having a melting point of 95 ° C. (decomposition).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.60-1.79 (4H, m), 2.21 (1H, br), 2.37 (3H, s), 2.52 (2H, t, J = 7.4Hz), 2.65 ( 2H, m), 2.88-3.26 (6H, m), 3.58 (2H, t, J = 5.8Hz), 4.10 (2H, s), 7.12-7.35 (5H, m), 7.71-7.81 (2H, m) .

実施例２１５で得た5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]-1-(1,2,3,4-テトラヒドロ-7-イソキノリニル)-1-ペンタノンを用いて、実施例２０７と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.60-1.79 (4H, m), 2.37 (3H, s), 2.52 (2H, t, J = 7.4Hz), 2.65 (2H, m), 2.87 (3H, s), 2.88-3.26 (6H, m), 3.58 (2H, t, J = 5.8Hz), 4.50 (2H, s), 7.12-7.35 (5H, m), 7.71-7.81 (2H, m). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- [2- (methylsulfonyl) -1,2,3,4-tetrahydro-7-isoquinolinyl] -1-pentanone hydrochloride

Using 5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] -1- (1,2,3,4-tetrahydro-7-isoquinolinyl) -1-pentanone obtained in Example 215, The title compound was obtained as a pale-yellow amorphous powder by the same operation as in Example 207.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.60-1.79 (4H, m), 2.37 (3H, s), 2.52 (2H, t, J = 7.4 Hz), 2.65 (2H, m), 2.87 ( 3H, s), 2.88-3.26 (6H, m), 3.58 (2H, t, J = 5.8Hz), 4.50 (2H, s), 7.12-7.35 (5H, m), 7.71-7.81 (2H, m) .

実施例２１５で得た5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]-1-(1,2,3,4-テトラヒドロ-7-イソキノリニル)-1-ペンタノンを用いて、実施例２０８と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.17 (3H, t, J = 5.8Hz), 1.57-1.78 (4H, m), 2.35 (3H, s), 2.48 (2H, t, J = 6.6Hz), 2.63 (2H, m), 2.89-2.99 (6H, m), 3.30-3.34 (2H, m), 3.64 (2H, t, J = 5.4Hz), 4.47 (1H, m), 4.58 (2H, s), 7.13-7.34 (5H, m), 7.73-7.79 (2H, m). 7- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -N-ethyl-3,4-dihydro-2 (1H) -isoquinolinecarboxamide hydrochloride

Using 5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] -1- (1,2,3,4-tetrahydro-7-isoquinolinyl) -1-pentanone obtained in Example 215, The same operation as in Example 208 was performed to give the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.17 (3H, t, J = 5.8 Hz), 1.57-1.78 (4H, m), 2.35 (3H, s), 2.48 (2H, t, J = 6.6 Hz), 2.63 (2H, m), 2.89-2.99 (6H, m), 3.30-3.34 (2H, m), 3.64 (2H, t, J = 5.4Hz), 4.47 (1H, m), 4.58 (2H , s), 7.13-7.34 (5H, m), 7.73-7.79 (2H, m).

参考例１２５で得た1-(2-アセチル-1,2,3,4-テトラヒドロ-7-イソキノリニル)-5-クロロ-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点78℃(分解)の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.79 (4H, m), 2.19 (3H, s), 2.37 (1H, br), 2.48 (2H, t, J = 7.0Hz), 2.57-2.65 (2H, m), 2.87-2.98 (6H, m), 3.69 (2H, t, J = 5.8Hz), 4.67 (2H, s), 7.11-7.34 (5H, m), 7.74-7.80 (2H, m). 1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-{[2- (2-chlorophenyl) ethyl] amino} -1-pentanone hydrochloride

Using 1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-chloro-1-pentanone and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 125, Reference Example The title compound was obtained as colorless crystals having a melting point of 78 ° C. (decomposition) by sequentially performing the same operations as in 19 and Example 1.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.79 (4H, m), 2.19 (3H, s), 2.37 (1H, br), 2.48 (2H, t, J = 7.0 Hz), 2.57- 2.65 (2H, m), 2.87-2.98 (6H, m), 3.69 (2H, t, J = 5.8Hz), 4.67 (2H, s), 7.11-7.34 (5H, m), 7.74-7.80 (2H, m).

参考例１２５で得た1-(2-アセチル-1,2,3,4-テトラヒドロ-7-イソキノリニル)-5-クロロ-1-ペンタノンおよび2-(2-メトキシフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点78℃(分解)の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.79 (4H, m), 2.19 (3H, s), 2.37 (1H, br), 2.48 (2H, t, J = 7.0Hz), 2.57-2.65 (2H, m), 2.87-2.98 (6H, m), 3.69 (2H, t, J = 5.8Hz), 3.80 (3H, s), 4.67 (2H, s), 7.11-7.34 (5H, m), 7.74-7.80 (2H, m). 1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-{[2- (2-methoxyphenyl) ethyl] amino} -1-pentanone hydrochloride

Using 1- (2-acetyl-1,2,3,4-tetrahydro-7-isoquinolinyl) -5-chloro-1-pentanone and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 125, The title compound was obtained as colorless crystals having a melting point of 78 ° C. (decomposition) by sequentially performing the same operations as in Example 19 and Example 1.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.79 (4H, m), 2.19 (3H, s), 2.37 (1H, br), 2.48 (2H, t, J = 7.0 Hz), 2.57- 2.65 (2H, m), 2.87-2.98 (6H, m), 3.69 (2H, t, J = 5.8Hz), 3.80 (3H, s), 4.67 (2H, s), 7.11-7.34 (5H, m) , 7.74-7.80 (2H, m).

参考例１４８で得た2-(2-クロロフェニル)エチル[5-(2,2-ジオキシド-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール-5-イル)-5-オキソペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を無色結晶として得た。
MS m/z: 408 [M+H]⁺ 5-{[2- (2-Chlorophenyl) ethyl] amino} -1- (2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone hydrochloride

2- (2-Chlorophenyl) ethyl [5- (2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -5-oxopentyl] carbamine obtained in Reference Example 148 The title compound was obtained as colorless crystals by operations similar to those of Example 1 using tert-butyl acid.
MS m / z: 408 [M + H] ⁺

参考例１４９で得た2-(2-クロロフェニル)エチル[5-(1,3-ジメチル-2,2-ジオキシド-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール-5-イル)-5-オキソペンチル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を融点149-150℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.61-1.80 (5H, m), 2.48-2.65 (4H, m), 2.65-2.99 (4H, m), 3.34 (3H, s), 3.35 (3H, s), 6.75 (1H, d, J = 8.4Hz), 7.12-7.39 (5H, m), 7.67 (1H, d, J = 8.4Hz). 5-{[2- (2-chlorophenyl) ethyl] amino} -1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone hydrochloride

2- (2-Chlorophenyl) ethyl [5- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl)-obtained in Reference Example 149 The title compound was obtained as colorless crystals with a melting point of 149-150 ° C. by carrying out the same operation as in Example 1 using tert-butyl 5-oxopentyl] carbamate.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.61-1.80 (5H, m), 2.48-2.65 (4H, m), 2.65-2.99 (4H, m), 3.34 (3H, s), 3.35 (3H , s), 6.75 (1H, d, J = 8.4Hz), 7.12-7.39 (5H, m), 7.67 (1H, d, J = 8.4Hz).

参考例１２９で得た5-クロロ-1-(1,3-ジメチル-2,2-ジオキシド-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール-5-イル)-1-ペンタノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.61-1.80 (4H, m), 2.45 (3H, s), 2.48-2.65 (4H, m), 2.65-2.99 (4H, m), 3.34 (3H, s), 3.35 (3H, s), 6.75 (1H, d, J = 8.4Hz), 7.12-7.39 (5H, m), 7.67 (1H, d, J = 8.4Hz). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazole-5 -Il) -1-pentanone hydrochloride

5-chloro-1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone and N obtained in Reference Example 129 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using-[2- (2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.61-1.80 (4H, m), 2.45 (3H, s), 2.48-2.65 (4H, m), 2.65-2.99 (4H, m), 3.34 (3H , s), 3.35 (3H, s), 6.75 (1H, d, J = 8.4Hz), 7.12-7.39 (5H, m), 7.67 (1H, d, J = 8.4Hz).

参考例１２９で得た5-クロロ-1-(1,3-ジメチル-2,2-ジオキシド-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール-5-イル)-1-ペンタノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.60-1.80 (4H, m), 2.34 (3H, s), 2.46-2.64 (4H, m), 2.77-2.84 (2H, m), 2.96 (2H, t, J = 7.0Hz), 3.34 (3H, s), 3.35 (3H, s), 3.81 (3H, s), 6.75 (1H, d, J = 8.2Hz), 6.82-6.91 (2H, m), 7.13-7.22 (2H, m), 7.38 (1H, s), 7.67 (1H, d, J = 8.2Hz). 1- (1,3-Dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -5-[[2- (2-methoxyphenyl) ethyl] ( Methyl) amino] -1-pentanone hydrochloride

5-chloro-1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone and N obtained in Reference Example 129 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using-[2- (2-methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.60-1.80 (4H, m), 2.34 (3H, s), 2.46-2.64 (4H, m), 2.77-2.84 (2H, m), 2.96 (2H , t, J = 7.0Hz), 3.34 (3H, s), 3.35 (3H, s), 3.81 (3H, s), 6.75 (1H, d, J = 8.2Hz), 6.82-6.91 (2H, m) , 7.13-7.22 (2H, m), 7.38 (1H, s), 7.67 (1H, d, J = 8.2Hz).

参考例１３３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.77 (4H, m), 2.14 (2H, m), 2.35 (3H, s), 2.49 (2H, m), 2.58 (2H, m), 2.87-3.00 (6H, m), 3.89 (2H, m), 7.11-7.35 (5H, m), 7.58 (1H, m), 10.91 (1H, s). 8- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one Hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and N- [2- (2) obtained in Reference Example 133 The title compound was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.77 (4H, m), 2.14 (2H, m), 2.35 (3H, s), 2.49 (2H, m), 2.58 (2H, m), 2.87-3.00 (6H, m), 3.89 (2H, m), 7.11-7.35 (5H, m), 7.58 (1H, m), 10.91 (1H, s).

参考例１３３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点187℃(分解)の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.77 (4H, m), 2.16 (2H, m), 2.36 (3H, s), 2.48-2.67 (4H, m), 2.78-3.00 (6H, m), 3.81 (3H, s), 3.88 (2H, m), 6.81-6.90 (3H, m), 7.12-7.16 (2H, m), 7.49 (1H, m), 7.58 (1H, m). 8- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H)- On hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and N- [2- (2) obtained in Reference Example 133 The title compound was obtained as colorless crystals having a melting point of 187 ° C. (decomposition) by performing the same operation as in Example 9 using -methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.77 (4H, m), 2.16 (2H, m), 2.36 (3H, s), 2.48-2.67 (4H, m), 2.78-3.00 (6H , m), 3.81 (3H, s), 3.88 (2H, m), 6.81-6.90 (3H, m), 7.12-7.16 (2H, m), 7.49 (1H, m), 7.58 (1H, m).

参考例１３４で得た8-(5-クロロペンタノイル)-1-メチル-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.78 (4H, m), 2.10 (2H, m), 2.34 (3H, s), 2.48 (2H, m), 2.60 (2H, m), 2.86-3.00 (5H, m), 3.22 (1H, m), 3.44 (3H, s), 3.84 (2H, m), 6.87 (1H, t, J = 8.4Hz), 7.11-7.34 (4H, m), 7.63 (1H, t, J = 8.4Hz). 8- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 ( 1H) -one hydrochloride

8- (5-Chloropentanoyl) -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and N- [obtained in Reference Example 134 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.78 (4H, m), 2.10 (2H, m), 2.34 (3H, s), 2.48 (2H, m), 2.60 (2H, m), 2.86-3.00 (5H, m), 3.22 (1H, m), 3.44 (3H, s), 3.84 (2H, m), 6.87 (1H, t, J = 8.4Hz), 7.11-7.34 (4H, m) , 7.63 (1H, t, J = 8.4Hz).

参考例１３４で得た8-(5-クロロペンタノイル)-1-メチル-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.59-1.78 (4H, m), 2.10 (2H, m), 2.34 (3H, s), 2.45-2.63 (5H, m), 2.78 (2H, m), 2.93 (2H, m), 3.22 (1H, m), 3.44 (3H, s), 3.82 (3H, s), 3.88 (2H, m), 6.82-6.91 (3H, m), 7.12-7.34 (2H, m), 7.63 (1H, t, J = 8.4Hz). 8- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H) -one hydrochloride

8- (5-Chloropentanoyl) -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and N- [obtained in Reference Example 134 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using 2- (2-methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.59-1.78 (4H, m), 2.10 (2H, m), 2.34 (3H, s), 2.45-2.63 (5H, m), 2.78 (2H, m ), 2.93 (2H, m), 3.22 (1H, m), 3.44 (3H, s), 3.82 (3H, s), 3.88 (2H, m), 6.82-6.91 (3H, m), 7.12-7.34 ( 2H, m), 7.63 (1H, t, J = 8.4Hz).

参考例１５０で得た(±)-2-(2-クロロフェニル)エチル[3-(1,3-ジメチル-2,5-ジオキソ-2,3,5,6,7,8-ヘキサヒドロ-1H-ナフト[2,3-d]イミダゾール-6-イル)プロピル]カルバミン酸 tert-ブチルを用いて、実施例１と同様の操作を行うことにより、表題化合物を融点201-203℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.68 (4H, m), 1.93 (3H, m), 2.25 (1H, m), 2.51 (2H, m), 2.65 (2H, m), 2.90 (2H, m), 3.03 (2H, m), 3.42 (3H, s), 3.43 (3H, s), 6.76 (1H, s), 7.11-7.34 (4H, m), 7.65 (1H, s). (±) -6- (3-{[2- (2-chlorophenyl) ethyl] amino} propyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d ] Imidazole-2,5-dione hydrochloride

(±) -2- (2-Chlorophenyl) ethyl [3- (1,3-dimethyl-2,5-dioxo-2,3,5,6,7,8-hexahydro-1H-] obtained in Reference Example 150 The title compound is obtained as colorless crystals with a melting point of 201-203 ° C. by conducting the same operation as in Example 1 using tert-butyl naphtho [2,3-d] imidazol-6-yl) propyl] carbamate. It was.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.68 (4H, m), 1.93 (3H, m), 2.25 (1H, m), 2.51 (2H, m), 2.65 (2H, m), 2.90 (2H, m), 3.03 (2H, m), 3.42 (3H, s), 3.43 (3H, s), 6.76 (1H, s), 7.11-7.34 (4H, m), 7.65 (1H, s) .

参考例１４１で得た(±)-6-(3-クロロプロピル)-1,3-ジメチル-3,6,7,8-テトラヒドロ-1H-ナフト[2,3-d]イミダゾール-2,5-ジオンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点201℃(分解)の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.68 (4H, m), 1.93 (2H, m), 2.25 (1H, m), 2.36 (3H, s), 2.51 (2H, m), 2.65 (2H, m), 2.90 (2H, m), 3.03 (2H, m), 3.42 (3H, s), 3.43 (3H, s), 6.76 (1H, s), 7.11-7.34 (4H, m), 7.65 (1H, s). (±) -6- {3-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] propyl} -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2, 3-d] imidazole-2,5-dione hydrochloride

(±) -6- (3-Chloropropyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5 obtained in Reference Example 141 The title compound was obtained as colorless crystals with a melting point of 201 ° C. (decomposition) by conducting the same operation as in Example 9 using 2-dione and N- [2- (2-chlorophenyl) ethyl] -N-methylamine. It was.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.68 (4H, m), 1.93 (2H, m), 2.25 (1H, m), 2.36 (3H, s), 2.51 (2H, m), 2.65 (2H, m), 2.90 (2H, m), 3.03 (2H, m), 3.42 (3H, s), 3.43 (3H, s), 6.76 (1H, s), 7.11-7.34 (4H, m) , 7.65 (1H, s).

参考例１４１で得た(±)-6-(3-クロロプロピル)-1,3-ジメチル-3,6,7,8-テトラヒドロ-1H-ナフト[2,3-d]イミダゾール-2,5-ジオンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点190-191℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.56-1.67 (4H, m), 1.94 (2H, m), 2.24 (1H, m), 2.36 (3H, s), 2.48 (2H, m), 2.61 (2H, m), 2.80 (2H, m), 3.04 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 3.82 (3H, s), 6.76-6.91 (3H, m), 7.13-7.22 (2H, m), 7.65 (1H, s). (±) -6- {3-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] propyl} -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2 , 3-d] imidazole-2,5-dione hydrochloride

(±) -6- (3-Chloropropyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5 obtained in Reference Example 141 The title compound was obtained as colorless crystals having a melting point of 190-191 ° C. by conducting the same operation as in Example 9 using N-dione and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine. It was.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.56-1.67 (4H, m), 1.94 (2H, m), 2.24 (1H, m), 2.36 (3H, s), 2.48 (2H, m), 2.61 (2H, m), 2.80 (2H, m), 3.04 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 3.82 (3H, s), 6.76-6.91 (3H, m) , 7.13-7.22 (2H, m), 7.65 (1H, s).

参考例１４２で得た(±)-6-(4-クロロブチル)-1,3-ジメチル-3,6,7,8-テトラヒドロ-1H-ナフト[2,3-d]イミダゾール-2,5-ジオンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.68 (6H, m), 1.98 (2H, m), 2.22 (1H, m), 2.38 (1H, br), 2.41-2.50 (2H, m), 2.57-2.65 (2H, m), 2.87-2.95 (2H, m), 2.99-3.06 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 6.75 (1H, s), 7.11-7.34 (4H, m), 7.65 (1H, s). (±) -6- (4-{[2- (2-chlorophenyl) ethyl] amino} butyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d ] Imidazole-2,5-dione hydrochloride

(±) -6- (4-Chlorobutyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5- obtained in Reference Example 142 The title compound was obtained as a pale yellow amorphous powder by sequentially performing the same operations as in Reference Example 19 and Example 1 using dione and 2- (2-chlorophenyl) ethylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.68 (6H, m), 1.98 (2H, m), 2.22 (1H, m), 2.38 (1H, br), 2.41-2.50 (2H, m ), 2.57-2.65 (2H, m), 2.87-2.95 (2H, m), 2.99-3.06 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 6.75 (1H, s), 7.11-7.34 (4H, m), 7.65 (1H, s).

参考例１４２で得た(±)-6-(4-クロロブチル)-1,3-ジメチル-3,6,7,8-テトラヒドロ-1H-ナフト[2,3-d]イミダゾール-2,5-ジオンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点202-204℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.68 (6H, m), 1.98 (2H, m), 2.22 (1H, m), 2.34 (3H, s), 2.41-2.50 (2H, m), 2.57-2.65 (2H, m), 2.87-2.95 (2H, m), 2.99-3.06 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 6.75 (1H, s), 7.11-7.34 (4H, m), 7.65 (1H, s). (±) -6- {4-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] butyl} -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2, 3-d] imidazole-2,5-dione hydrochloride

(±) -6- (4-Chlorobutyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5- obtained in Reference Example 142 The same operation as in Example 9 was carried out using dione and N- [2- (2-chlorophenyl) ethyl] -N-methylamine to give the title compound as colorless crystals having a melting point of 202-204 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.68 (6H, m), 1.98 (2H, m), 2.22 (1H, m), 2.34 (3H, s), 2.41-2.50 (2H, m ), 2.57-2.65 (2H, m), 2.87-2.95 (2H, m), 2.99-3.06 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 6.75 (1H, s), 7.11-7.34 (4H, m), 7.65 (1H, s).

参考例１４２で得た(±)-6-(4-クロロブチル)-1,3-ジメチル-3,6,7,8-テトラヒドロ-1H-ナフト[2,3-d]イミダゾール-2,5-ジオンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.58-1.68 (6H, m), 1.98 (2H, m), 2.22 (1H, m), 2.35 (3H, s), 2.44-2.52 (2H, m), 2.57-2.65 (2H, m), 2.75-2.84 (2H, m), 3.01-3.06 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 3.82 (3H, s), 6.74-6.91 (3H, m), 7.13-7.21 (2H, m), 7.65 (1H, s). (±) -6- {4-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] butyl} -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2 , 3-d] imidazole-2,5-dione hydrochloride

(±) -6- (4-Chlorobutyl) -1,3-dimethyl-3,6,7,8-tetrahydro-1H-naphtho [2,3-d] imidazole-2,5- obtained in Reference Example 142 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using dione and N- [2- (2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.58-1.68 (6H, m), 1.98 (2H, m), 2.22 (1H, m), 2.35 (3H, s), 2.44-2.52 (2H, m ), 2.57-2.65 (2H, m), 2.75-2.84 (2H, m), 3.01-3.06 (2H, m), 3.41 (3H, s), 3.42 (3H, s), 3.82 (3H, s), 6.74-6.91 (3H, m), 7.13-7.21 (2H, m), 7.65 (1H, s).

参考例１４６で得た(±)-2-(3-クロロプロピル)-5,6-ジメトキシ-1-インダノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.48 (1H, m), 1.59 (2H, m), 1.94 (1H, m), 2.34 (3H, s), 2.47 (2H, t, J = 7.6Hz), 2.58-2.75 (4H, m), 2.90 (2H, m), 3.24 (1H, dd, J = 17.1, 7.8Hz), 3.90 (3H, s), 3.96 (3H, s), 6.86 (1H, s), 7.08-7.32 (5H, m). (±) -2- {3-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] propyl} -5,6-dimethoxy-1-indanone hydrochloride

Using (±) -2- (3-chloropropyl) -5,6-dimethoxy-1-indanone and N- [2- (2-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 146, The same operation as in Example 9 was performed to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.48 (1H, m), 1.59 (2H, m), 1.94 (1H, m), 2.34 (3H, s), 2.47 (2H, t, J = 7.6 Hz), 2.58-2.75 (4H, m), 2.90 (2H, m), 3.24 (1H, dd, J = 17.1, 7.8Hz), 3.90 (3H, s), 3.96 (3H, s), 6.86 (1H , s), 7.08-7.32 (5H, m).

参考例１４６で得た(±)-2-(3-クロロプロピル)-5,6-ジメトキシ-1-インダノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.46-1.70 (4H, m), 1.95 (2H, m), 2.33 (3H, s), 2.44-2.83 (6H, m), 3.25 (1H, dd, J = 17.2, 7.4Hz), 3.81 (3H, s), 3.91 (3H, s), 3.97 (3H, s), 6.81-6.90 (3H, m), 7.12-7.21 (3H, m). (±) -5,6-Dimethoxy-2- {3-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] propyl} -1-indanone hydrochloride

Using (±) -2- (3-chloropropyl) -5,6-dimethoxy-1-indanone and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 146 The title compound was obtained as a pale yellow amorphous powder by the same operation as in Example 9.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.46-1.70 (4H, m), 1.95 (2H, m), 2.33 (3H, s), 2.44-2.83 (6H, m), 3.25 (1H, dd , J = 17.2, 7.4Hz), 3.81 (3H, s), 3.91 (3H, s), 3.97 (3H, s), 6.81-6.90 (3H, m), 7.12-7.21 (3H, m).

参考例１４７で得た(±)-2-(4-クロロブチル)-5,6-ジメトキシ-1-インダノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.45-1.59 (4H, m), 1.99 (2H, m), 2.33 (3H, s), 2.45 (2H, t, J = 7.6Hz), 2.54-2.62 (4H, m), 2.80 (2H, m), 3.25 (1H, dd, J = 17.2, 7.4Hz), 3.92 (3H, s), 3.96 (3H, s), 6.87 (1H, s), 7.11-7.34 (5H, m). (±) -2- {4-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] butyl} -5,6-dimethoxy-1-indanone hydrochloride

Using (±) -2- (4-chlorobutyl) -5,6-dimethoxy-1-indanone and N- [2- (2-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 147 The title compound was obtained as a pale yellow amorphous powder by the same operation as in Example 9.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.45-1.59 (4H, m), 1.99 (2H, m), 2.33 (3H, s), 2.45 (2H, t, J = 7.6 Hz), 2.54- 2.62 (4H, m), 2.80 (2H, m), 3.25 (1H, dd, J = 17.2, 7.4Hz), 3.92 (3H, s), 3.96 (3H, s), 6.87 (1H, s), 7.11 -7.34 (5H, m).

参考例１４７で得た(±)-2-(4-クロロブチル)-5,6-ジメトキシ-1-インダノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.45-1.59 (4H, m), 1.99 (2H, m), 2.32 (3H, s), 2.45 (2H, t, J = 7.6Hz), 2.54-2.62 (4H, m), 2.80 (2H, m), 3.25 (1H, dd, J = 17.2, 7.4Hz), 3.80 (3H, s), 3.90 (3H, s), 3.96 (3H, s), 6.81-6.91 (3H, m), 7.13-7.21 (3H, m). (±) -5,6-Dimethoxy-2- {4-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] butyl} -1-indanone hydrochloride

Using (±) -2- (4-chlorobutyl) -5,6-dimethoxy-1-indanone and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine obtained in Reference Example 147, The same operation as in Example 9 was performed to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.45-1.59 (4H, m), 1.99 (2H, m), 2.32 (3H, s), 2.45 (2H, t, J = 7.6Hz), 2.54- 2.62 (4H, m), 2.80 (2H, m), 3.25 (1H, dd, J = 17.2, 7.4Hz), 3.80 (3H, s), 3.90 (3H, s), 3.96 (3H, s), 6.81 -6.91 (3H, m), 7.13-7.21 (3H, m).

参考例１３３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよび5-メトキシ-1,2,3,4-テトラヒドロイソキノリンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.69-1.83 (4H, m), 2.10 (2H, m), 2.57 (2H, t, J = 6.0Hz), 2.86 (2H, m), 3.01 (2H, m), 3.18 (2H, m), 3.61 (2H, s), 3.80 (3H, s), 3.72-3.90 (4H, m), 6.63-6.69 (2H, m), 6.86 (1H, t, J = 8.4Hz), 7.08 (1H, t, J = 8.0Hz), 7.56 (1H, m), 9.56 (1H, br). 8- [5- (5-Methoxy-3,4-dihydro-2 (1H) -isoquinolinyl) pentanoyl] -5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H) -On hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and 5-methoxy-1,2 obtained in Reference Example 133 , 3,4-Tetrahydroisoquinoline was used in the same manner as in Example 9 to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.69-1.83 (4H, m), 2.10 (2H, m), 2.57 (2H, t, J = 6.0 Hz), 2.86 (2H, m), 3.01 ( 2H, m), 3.18 (2H, m), 3.61 (2H, s), 3.80 (3H, s), 3.72-3.90 (4H, m), 6.63-6.69 (2H, m), 6.86 (1H, t, J = 8.4Hz), 7.08 (1H, t, J = 8.0Hz), 7.56 (1H, m), 9.56 (1H, br).

参考例１３４で得た8-(5-クロロペンタノイル)-1-メチル-5,6-ジヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-2(1H)-オンおよび5-メトキシ-1,2,3,4-テトラヒドロイソキノリンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.69-1.83 (4H, m), 2.05 (2H, m), 2.54 (2H, t, J = 6.0Hz), 2.70-2.87 (4H, m), 3.00 (2H, m), 3.22 (2H, t, J = 6.0Hz), 3.42 (3H, s), 3.59 (2H, s), 3.80 (3H, s), 3.81-3.88 (2H, m), 6.64 (2H, t, J = 8.1Hz), 6.67 (1H, d, J = 8.1Hz), 7.80 (1H, t, J = 7.8Hz), 7.56 (1H, m). 8- [5- (5-Methoxy-3,4-dihydro-2 (1H) -isoquinolinyl) pentanoyl] -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline- 2 (1H) -one hydrochloride

8- (5-Chloropentanoyl) -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinolin-2 (1H) -one and 5-methoxy obtained in Reference Example 134 The same operation as in Example 9 was performed using -1,2,3,4-tetrahydroisoquinoline to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.69-1.83 (4H, m), 2.05 (2H, m), 2.54 (2H, t, J = 6.0 Hz), 2.70-2.87 (4H, m), 3.00 (2H, m), 3.22 (2H, t, J = 6.0Hz), 3.42 (3H, s), 3.59 (2H, s), 3.80 (3H, s), 3.81-3.88 (2H, m), 6.64 (2H, t, J = 8.1Hz), 6.67 (1H, d, J = 8.1Hz), 7.80 (1H, t, J = 7.8Hz), 7.56 (1H, m).

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オンおよび5-クロロ-1,2,3,4-テトラヒドロイソキノリンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.68-1.86 (4H, m), 2.01 (2H, m), 2.55 (2H, t, J = 7.2Hz), 2.70-2.83 (6H, m), 2.97 (2H, t, J = 7.0Hz), 3.50 (2H, s), 3.58 (2H, s), 3.72 (2H, t, J = 6.0Hz), 6.91 (1H, d, J = 7.2Hz), 7.04 (1H, t, J = 7.8Hz), 7.17 (1H, t, J = 7.6Hz), 7.72 (2H, s). 8- [5- (5-Chloro-3,4-dihydro-2 (1H) -isoquinolinyl) pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H) -On hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and 5-chloro-1,2 obtained in Reference Example 3 , 3,4-Tetrahydroisoquinoline was used in the same manner as in Example 9 to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.68-1.86 (4H, m), 2.01 (2H, m), 2.55 (2H, t, J = 7.2 Hz), 2.70-2.83 (6H, m), 2.97 (2H, t, J = 7.0Hz), 3.50 (2H, s), 3.58 (2H, s), 3.72 (2H, t, J = 6.0Hz), 6.91 (1H, d, J = 7.2Hz), 7.04 (1H, t, J = 7.8Hz), 7.17 (1H, t, J = 7.6Hz), 7.72 (2H, s).

参考例３で得た8-(5-クロロペンタノイル)-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij ]キノリン-2(1H)-オンおよび5-メトキシ-1,2,3,4-テトラヒドロイソキノリンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.66-1.85 (4H, m), 1.98 (2H, m), 2.54 (2H, t, J = 7.0Hz), 2.71-2.81 (6H, m), 2.97 (2H, t, J = 6.6Hz), 3.48 (2H, s), 3.58 (2H, s), 3.72 (2H, t, J = 6.4Hz), 3.80 (3H, s), 6.64 (2H, t, J = 7.0Hz), 7.08 (1H, t, J = 7.6Hz), 7.73 (2H, s). 8- [5- (5-Methoxy-3,4-dihydro-2 (1H) -isoquinolinyl) pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H) -On hydrochloride

8- (5-Chloropentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one and 5-methoxy-1,2 obtained in Reference Example 3 , 3,4-Tetrahydroisoquinoline was used in the same manner as in Example 9 to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.66-1.85 (4H, m), 1.98 (2H, m), 2.54 (2H, t, J = 7.0 Hz), 2.71-2.81 (6H, m), 2.97 (2H, t, J = 6.6Hz), 3.48 (2H, s), 3.58 (2H, s), 3.72 (2H, t, J = 6.4Hz), 3.80 (3H, s), 6.64 (2H, t , J = 7.0Hz), 7.08 (1H, t, J = 7.6Hz), 7.73 (2H, s).

参考例１２９で得た5-クロロ-1-(1,3-ジメチル-2,2-ジオキシド-1,3-ジヒドロ-2,1,3-ベンゾチアジアゾール-5-イル)-1-ペンタノンおよび5-メトキシ-1,2,3,4-テトラヒドロイソキノリンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.68-1.85 (4H, m), 2.58 (2H, t, J = 7.0Hz), 2.72 (4H, m), 2.98 (2H, t, J = 7.4Hz), 3.29 (3H, s), 3.30 (3H, s), 3.58 (2H, s), 3.79 (3H, s), 6.61-6.66 (3H, m), 7.08 (1H, t, J = 8.0Hz), 7.34 (1H, m), 7.65 (1H, m). 1- (1,3-Dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -5- (5-methoxy-3,4-dihydro-2 ( 1H) -Isoquinolinyl) -1-pentanone hydrochloride

5-chloro-1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1-pentanone obtained in Reference Example 129 and 5 The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 9 using -methoxy-1,2,3,4-tetrahydroisoquinoline.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.68-1.85 (4H, m), 2.58 (2H, t, J = 7.0 Hz), 2.72 (4H, m), 2.98 (2H, t, J = 7.4 Hz), 3.29 (3H, s), 3.30 (3H, s), 3.58 (2H, s), 3.79 (3H, s), 6.61-6.66 (3H, m), 7.08 (1H, t, J = 8.0Hz ), 7.34 (1H, m), 7.65 (1H, m).

参考例１４７で得た(±)-2-(4-クロロブチル)-5,6-ジメトキシ-1-インダノンおよび5-クロロ-1,2,3,4-テトラヒドロイソキノリンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.49-1.68 (4H, m), 1.95 (2H, m), 2.52 (2H, t, J = 7.6Hz), 2.62-2.78 (4H, m), 2.87 (2H, m), 3.24 (1H, dd, J = 16.8, 7.2Hz), 3.59 (2H, s), 3.90 (3H, s), 3.96 (3H, s), 6.87-6.94 (2H, m), 7.05 (1H, t, J = 7.8Hz), 7.18 (2H, m). (±) -2- [4- (5-Chloro-3,4-dihydro-2 (1H) -isoquinolinyl) butyl] -5,6-dimethoxy-1-indanone

Example 9 and (±) -2- (4-chlorobutyl) -5,6-dimethoxy-1-indanone and 5-chloro-1,2,3,4-tetrahydroisoquinoline obtained in Reference Example 147 were used. By carrying out the same operation, the title compound was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.49-1.68 (4H, m), 1.95 (2H, m), 2.52 (2H, t, J = 7.6 Hz), 2.62-2.78 (4H, m), 2.87 (2H, m), 3.24 (1H, dd, J = 16.8, 7.2Hz), 3.59 (2H, s), 3.90 (3H, s), 3.96 (3H, s), 6.87-6.94 (2H, m) , 7.05 (1H, t, J = 7.8Hz), 7.18 (2H, m).

参考例１４７で得た(±)-2-(4-クロロブチル)-5,6-ジメトキシ-1-インダノンおよび5-メトキシ-1,2,3,4-テトラヒドロイソキノリンを用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.50-1.68 (4H, m), 1.97 (2H, m), 2.51 (2H, t, J = 8.2Hz), 2.62-2.76 (6H, m), 3.23 (1H, dd, J = 17.2, 7.6Hz), 3.59 (2H, s), 3.80 (3H, s), 3.90 (3H, s), 3.96 (3H, s), 6.62-6.67 (2H, m), 6.87 (1H, s), 7.08 (1H, t, J = 7.8Hz), 7.17 (1H, s). (±) -5,6-Dimethoxy-2- [4- (5-methoxy-3,4-dihydro-2 (1H) -isoquinolinyl) butyl] -1-indanone

Example 9 and (±) -2- (4-chlorobutyl) -5,6-dimethoxy-1-indanone and 5-methoxy-1,2,3,4-tetrahydroisoquinoline obtained in Reference Example 147 were used. By carrying out the same operation, the title compound was obtained as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.50-1.68 (4H, m), 1.97 (2H, m), 2.51 (2H, t, J = 8.2 Hz), 2.62-2.76 (6H, m), 3.23 (1H, dd, J = 17.2, 7.6Hz), 3.59 (2H, s), 3.80 (3H, s), 3.90 (3H, s), 3.96 (3H, s), 6.62-6.67 (2H, m) , 6.87 (1H, s), 7.08 (1H, t, J = 7.8Hz), 7.17 (1H, s).

参考例１５１で得た2-(1H-インドール-3-イル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(822mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点179-180℃の無色結晶(630mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.80-3.25 (12H, m), 3.98 (2H, t, J = 8.4Hz), 7.00 (1H, t, J = 7.8Hz), 7.09 (1H, t, J = 7.8Hz), 7.24 (1H, d, J = 2.1Hz), 7.37 (1H, d, J = 7.8Hz), 7.61 (1H, d, J = 7.8Hz), 7.73 (1H, s), 7.74 (1H, s), 9.00-9.20 (2H, br), 11.0 (1H, s). 8- (5-{[2- (1H-Indol-3-yl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

2- (1H-Indol-3-yl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-] obtained in Reference Example 151 ij] Quinolin-8-yl) pentyl] carbamate tert-butyl (822 mg) was used to give the title compound as colorless crystals (630 mg) having a melting point of 179-180 ° C. by the same procedure as in Example 1. It was.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.80-3.25 (12H, m), 3.98 (2H, t, J = 8.4Hz), 7.00 (1H, t, J = 7.8Hz), 7.09 (1H, t, J = 7.8Hz), 7.24 (1H, d, J = 2.1Hz), 7.37 (1H, d, J = 7.8Hz ), 7.61 (1H, d, J = 7.8Hz), 7.73 (1H, s), 7.74 (1H, s), 9.00-9.20 (2H, br), 11.0 (1H, s).

参考例１５２で得た(±)-2-ヒドロキシ-2-フェニルエチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(1.29g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を淡黄色結晶(680mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.90-3.25 (10H, m), 3.99 (2H, t, J = 8.4Hz), 4.98 (1H, d, J = 8.4Hz), 6.10-6.30 (1H, br), 7.30-7.50 (5H, m), 7.73 (1H, s), 7.74 (1H, s), 8.85-9.25 (2H, br). (±) -8- {5-[(2-hydroxy-2-phenylethyl) amino] pentanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-4 -On hydrochloride

(±) -2-Hydroxy-2-phenylethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] Quinolin-8-yl) pentyl] carbamate tert-butyl (1.29 g) was used for the same operation as in Example 1 to obtain the title compound as pale yellow crystals (680 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.90-3.25 (10H, m), 3.99 (2H, t, J = 8.4Hz), 4.98 (1H, d, J = 8.4Hz), 6.10-6.30 (1H, br), 7.30-7.50 (5H, m), 7.73 (1H, s), 7.74 (1H, s), 8.85- 9.25 (2H, br).

参考例１５３で得た(±)-2-ヒドロキシ-2-(3-ヒドロキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(201mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点178-179℃の無色結晶(169mg)として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.80-3.60 (10H, m), 3.99 (2H, t, J = 8.4Hz), 4.90 (1H, d, J = 9.9Hz), 5.90-6.30 (1H, br), 6.65-6.90 (3H, m), 7.16 (1H, t, J = 7.8Hz), 7.73 (1H, s), 7.74 (1H, s), 8.65-8.85 (1H, br), 9.00-9.25 (1H, br), 9.40-9.65 (1H, br). (±) -8- (5-{[2-hydroxy-2- (3-hydroxyphenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-4-one hydrochloride

(±) -2-Hydroxy-2- (3-hydroxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3] obtained in Reference Example 153 , 2,1-ij] Quinolin-8-yl) pentyl] carbamate tert-butyl (201 mg) was used for the same procedure as in Example 1 to give the title compound as colorless crystals having a melting point of 178-179 ° C. Obtained as (169 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.8Hz), 2.80-3.60 (10H, m), 3.99 (2H, t, J = 8.4Hz), 4.90 (1H, d, J = 9.9Hz), 5.90-6.30 (1H, br), 6.65-6.90 (3H, m), 7.16 (1H, t, J = 7.8Hz), 7.73 (1H, s), 7.74 (1H, s), 8.65-8.85 (1H, br), 9.00-9.25 (1H, br), 9.40-9.65 (1H, br).

参考例１５５で得た2-(2-クロロ-4-フルオロフェニル)エチル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(440mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(282mg) を融点128-129℃(分解)の淡黄色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.52-1.73 (4H, m), 1.90-1.94 (2H, m), 2.77 (2H, t, J = 7Hz), 2.95-3.09 (8H, m), 3.57 (2H, s), 3.60 (2H, t, J = 6Hz), 7.22 (1H, dt, J = 2.7, 8.5Hz), 7.43-7.47 (2H, m), 7.71 (1H, s), 7.75 (1H, s), 9.22 (2H, s).
IR (KBr) νcm^-1: 3491, 2945, 2774, 1712, 1671, 1604, 1495, 1346, 1153. 8- (5-{[2- (2-chloro-4-fluorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H) -On hydrochloride

2- (2-Chloro-4-fluorophenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1] obtained in Reference Example 155 -ij] quinolin-8-yl) pentyl] carbamic acid tert-butyl (440 mg) was used in the same manner as in Example 1 to obtain the title compound (282 mg) having a melting point of 128-129 ° C (decomposition). Obtained as pale yellow crystals.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.52-1.73 (4H, m), 1.90-1.94 (2H, m), 2.77 (2H, t, J = 7Hz), 2.95-3.09 (8H, m), 3.57 (2H, s), 3.60 (2H, t, J = 6Hz), 7.22 (1H, dt, J = 2.7, 8.5Hz), 7.43-7.47 (2H, m), 7.71 (1H, s), 7.75 ( 1H, s), 9.22 (2H, s).
IR (KBr) νcm ^-1 : 3491, 2945, 2774, 1712, 1671, 1604, 1495, 1346, 1153.

参考例１５６で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-クロロ-4-フルオロフェニル)エチル]カルバミン酸 tert-ブチル(540mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(275mg) を融点176-177℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.51-1.73 (4H, m), 2.18 (3H, s), 2.95-3.08 (8H, m), 3.17 (2H, t, J = 8.3Hz), 4.14 (2H, t, J = 8.5Hz), 7.22 (1H, dt, J = 2.7, 8.5Hz), 7.43-7.47 (2H, m), 7.82 (1H, s), 7.83 (1H, t, J = 8.0Hz), 8.08 (1H, d, J = 8.5Hz), 9.17 (2H, s).
IR (KBr) νcm^-1: 3436, 2954, 2780, 1667, 1604, 1494, 1442, 1403, 1338, 1260, 1233. 1- (1-Acetyl-2,3-dihydro-1H-indol-5-yl) -5-{[2- (2-chloro-4-fluorophenyl) ethyl] amino} pentan-1-one hydrochloride

5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-chloro-4-fluorophenyl) ethyl] carbamic acid tert obtained in Reference Example 156 The title compound (275 mg) was obtained as colorless crystals having a melting point of 176-177 ° C. (decomposition) by conducting the same operation as in Example 1 using -butyl (540 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.51-1.73 (4H, m), 2.18 (3H, s), 2.95-3.08 (8H, m), 3.17 (2H, t, J = 8.3Hz), 4.14 (2H, t, J = 8.5Hz), 7.22 (1H, dt, J = 2.7, 8.5Hz), 7.43-7.47 (2H, m), 7.82 (1H, s), 7.83 (1H, t, J = 8.0 Hz), 8.08 (1H, d, J = 8.5Hz), 9.17 (2H, s).
IR (KBr) νcm ^-1 : 3436, 2954, 2780, 1667, 1604, 1494, 1442, 1403, 1338, 1260, 1233.

参考例１５７で得た2-(2-クロロ-4-フルオロフェニル)エチル[5-(1-メチル-2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)-5-オキソペンチル]カルバミン酸 tert-ブチル(460mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(356mg) を融点169-170℃(分解)の淡黄色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.58-1.65 (4H, m), 2.49 (2H, t, J = 7.0Hz), 2.83-3.04 (10H, m), 3.19 (3H, s), 7.09 (1H, d, J = 8.5Hz), 7.13 (1H, dt, J = 2.6, 8.5Hz), 7.33-7.40 (2H, m), 7.76 (1H, s), 7.80 (1H, d, J = 8.3Hz), 9.33 (2H, s).
IR (KBr) νcm^-1: 3433, 2953, 2790, 1673, 1603, 1494, 1354, 1128. 6- (5-{[2- (2-Chloro-4-fluorophenyl) ethyl] amino} pentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one hydrochloride

2- (2-Chloro-4-fluorophenyl) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxo obtained in Reference Example 157 The same operation as in Example 1 was carried out using pentyl] carbamate tert-butyl (460 mg) to obtain the title compound (356 mg) as pale yellow crystals having a melting point of 169-170 ° C. (decomposition).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.58-1.65 (4H, m), 2.49 (2H, t, J = 7.0Hz), 2.83-3.04 (10H, m), 3.19 (3H, s), 7.09 (1H, d, J = 8.5Hz), 7.13 (1H, dt, J = 2.6, 8.5Hz), 7.33-7.40 (2H, m), 7.76 (1H, s), 7.80 (1H, d, J = 8.3 Hz), 9.33 (2H, s).
IR (KBr) νcm ^-1 : 3433, 2953, 2790, 1673, 1603, 1494, 1354, 1128.

参考例１５８で得た5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル{2-[2-(トリフルオロメトキシ)フェニル]エチル}カルバミン酸 tert-ブチル(200mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(95mg) を融点71-72℃(分解)の淡黄色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.66-1.68 (4H, m), 1.89-1.95 (2H, m), 2.77 (2H, t, J = 6Hz), 2.97-3.06 (8H, m), 3.58 (2H, s), 3.61 (2H, t, J =6Hz), 7.35-7.47 (4H, m), 7.72 (1H, s), 7.76 (1H, s), 9.06 (2H, br.s).
IR (KBr) νcm^-1: 3422, 2943, 1711, 1605, 1496, 1344, 1256, 1154. 8- [5-({2- [2- (trifluoromethoxy) phenyl] ethyl} amino) pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H) -On hydrochloride

5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl {2- [obtained in Reference Example 158 2- (Trifluoromethoxy) phenyl] ethyl} carbamate tert-butyl (200 mg) was used in the same manner as in Example 1 to obtain the title compound (95 mg) having a melting point of 71-72 ° C. (decomposition). Obtained as pale yellow crystals.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.66-1.68 (4H, m), 1.89-1.95 (2H, m), 2.77 (2H, t, J = 6Hz), 2.97-3.06 (8H, m), 3.58 (2H, s), 3.61 (2H, t, J = 6Hz), 7.35-7.47 (4H, m), 7.72 (1H, s), 7.76 (1H, s), 9.06 (2H, br.s).
IR (KBr) νcm ^-1 : 3422, 2943, 1711, 1605, 1496, 1344, 1256, 1154.

参考例１５９で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル{2-[2-(トリフルオロメトキシ)フェニル]エチル}カルバミン酸 tert-ブチル(450mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(274mg) を融点180-182℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.65-1.71 (4H, m), 2.18 (3H, s), 2.96-3.07 (8H, m), 3.17 (2H, t, J = 8.3Hz), 4.14 (2H, t, J = 8.3Hz), 7.35-7.48 (4H, m), 7.82 (1H, s), 7.83 (1H, t, J = 8.3Hz), 8.08 (1H, d, J = 8.3Hz), 9.20 (2H, br.s).
IR (KBr) νcm^-1: 3432, 2953, 2766, 1676, 1601, 1492, 1442, 1398, 1260, 1177. 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-({2- [2- (trifluoromethoxy) phenyl] ethyl} amino) pentan-1-one hydrochloride

5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl {2- [2- (trifluoromethoxy) phenyl] ethyl} carbamic acid obtained in Reference Example 159 The title compound (274 mg) was obtained as colorless crystals having a melting point of 180-182 ° C. (decomposition) by performing the same operation as in Example 1 using -butyl (450 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.65-1.71 (4H, m), 2.18 (3H, s), 2.96-3.07 (8H, m), 3.17 (2H, t, J = 8.3Hz), 4.14 (2H, t, J = 8.3Hz), 7.35-7.48 (4H, m), 7.82 (1H, s), 7.83 (1H, t, J = 8.3Hz), 8.08 (1H, d, J = 8.3Hz) , 9.20 (2H, br.s).
IR (KBr) νcm ^-1 : 3432, 2953, 2766, 1676, 1601, 1492, 1442, 1398, 1260, 1177.

参考例１６０で得た5-(1-メチル-2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)-5-オキソペンチル{2-[2-(トリフルオロメトキシ)フェニル]エチル}カルバミン酸 tert-ブチル(435mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(237mg) を融点89-90℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.69 (4H, m), 2.58 (2H, t, J = 7.0Hz), 2.92-3.07 (10H, m), 3.28 (3H, s), 7.19 (1H, d, J = 8.5Hz), 7.35-7.48(4H, m), 7.84 (1H, s), 7.89 (1H, d, J = 8.3Hz), 9.11 (2H, br.s).
IR (KBr) νcm^-1: 3432, 2944, 1675, 1604, 1456, 1364, 1265, 1131. 1-Methyl-6- [5-({2- [2- (trifluoromethoxy) phenyl] ethyl} amino) pentanoyl] -3,4-dihydroquinolin-2 (1H) -one hydrochloride

5- (1-Methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl {2- [2- (trifluoromethoxy) phenyl] obtained in Reference Example 160 The title compound (237 mg) was obtained as colorless crystals having a melting point of 89-90 ° C. (decomposition) by performing the same operation as in Example 1 using tert-butyl ethyl} carbamate (435 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.69 (4H, m), 2.58 (2H, t, J = 7.0Hz), 2.92-3.07 (10H, m), 3.28 (3H, s), 7.19 (1H, d, J = 8.5Hz), 7.35-7.48 (4H, m), 7.84 (1H, s), 7.89 (1H, d, J = 8.3Hz), 9.11 (2H, br.s).
IR (KBr) νcm ^-1 : 3432, 2944, 1675, 1604, 1456, 1364, 1265, 1131.

参考例１６１で得た5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル{2-[2-(トリフルオロメトキシ)フェニル]エチル}カルバミン酸 tert-ブチル(240mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(127mg) を融点133-134℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.70-1.74 (4H, m), 2.98 (2H, br.s), 3.08-3.11 (6H, m), 3.36 (3H, s), 3.38 (3H, s), 7.24 (1H, d, J = 8.3Hz), 7.35-7.43 (3H, m), 7.46 (1H, dd, J = 2.2, 7.0Hz), 7.72 (1H, d, J = 1.5Hz), 7.80 (1H, dd, J = 1.5, 8.3Hz), 9.19 (2H, br.s).
IR (KBr) νcm^-1: 3496, 2954, 2782, 1720, 1675, 1513, 1456, 1255, 1213, 1178. 1,3-Dimethyl-5- [5-({2- [2- (trifluoromethoxy) phenyl] ethyl} amino) pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl {2- [2- (trifluoromethoxy)] obtained in Reference Example 161 The title compound (127 mg) was obtained as colorless crystals with a melting point of 133-134 ° C. (decomposition) by performing the same operation as in Example 1 using tert-butyl (phenyl) ethyl} carbamate (240 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.70-1.74 (4H, m), 2.98 (2H, br.s), 3.08-3.11 (6H, m), 3.36 (3H, s), 3.38 (3H, s), 7.24 (1H, d, J = 8.3Hz), 7.35-7.43 (3H, m), 7.46 (1H, dd, J = 2.2, 7.0Hz), 7.72 (1H, d, J = 1.5Hz), 7.80 (1H, dd, J = 1.5, 8.3Hz), 9.19 (2H, br.s).
IR (KBr) νcm ^-1 : 3496, 2954, 2782, 1720, 1675, 1513, 1456, 1255, 1213, 1178.

参考例１６２で得た3-(2-メトキシフェニル)プロピル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(160mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(113mg) を淡黄色非晶状粉末として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.64 (4H, br.s), 1.72-1.95 (4H, m), 2.59 (2H, t, J = 6Hz), 2.70-2.93 (6H, m), 2.98 (2H, br.s), 3.57 (2H, s), 3.60 (2H, br.s), 3.77 (3H, s), 6.87 (1H, t, J = 7.3Hz), 6.95 (1H, d, J = 7.6Hz), 7.14 (1H, d, J = 7.3Hz), 7.19 (1H, t, J = 7.6Hz), 7.71 (1H, s), 7.75 (1H, s), 8.81 (2H, br.s).
IR (KBr) νcm^-1: 3425, 2945, 1708, 1664, 1601, 1495, 1344, 1244, 1155, 759. 8- (5-{[3- (2-methoxyphenyl) propyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

3- (2-Methoxyphenyl) propyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 162 -8-yl) pentyl] carbamate tert-butyl (160 mg) was used for the same operation as in Example 1 to obtain the title compound (113 mg) as a pale yellow amorphous powder.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.64 (4H, br.s), 1.72-1.95 (4H, m), 2.59 (2H, t, J = 6Hz), 2.70-2.93 (6H, m), 2.98 (2H, br.s), 3.57 (2H, s), 3.60 (2H, br.s), 3.77 (3H, s), 6.87 (1H, t, J = 7.3Hz), 6.95 (1H, d, J = 7.6Hz), 7.14 (1H, d, J = 7.3Hz), 7.19 (1H, t, J = 7.6Hz), 7.71 (1H, s), 7.75 (1H, s), 8.81 (2H, br. s).
IR (KBr) νcm ^-1 : 3425, 2945, 1708, 1664, 1601, 1495, 1344, 1244, 1155, 759.

参考例１６３で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[3-(2-メトキシフェニル)プロピル]カルバミン酸 tert-ブチル(410mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(290mg) を融点165-166℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.68 (4H, m), 1.85-1.95 (2H, m), 2.18 (3H, s), 2.59 (2H, t, J = 7.3Hz), 2.79-2.87 (4H, m), 2.98 (2H, t, J = 7Hz), 3.16 (2H, t, J = 8.3Hz), 3.77 (3H, s), 4.13 (2H, t, J = 8.3Hz), 6.89 (1H, t, J = 7.6Hz), 6.94 (1H, d, J = 7.6Hz), 7.15 (1H, d, J = 7.6Hz), 7.19 (1H, t, J = 7.6Hz), 7.81 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.08 (1H, d, J = 8.3Hz), 9.00 (2H, br.s).
IR (KBr) νcm^-1: 3436, 2945, 1676, 1661, 1602, 1492, 1438, 1399, 1334, 1243, 754. 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-{[3- (2-methoxyphenyl) propyl] amino} pentan-1-one hydrochloride

Tert-Butyl (410 mg) of 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [3- (2-methoxyphenyl) propyl] carbamate obtained in Reference Example 163 ) To give the title compound (290 mg) as colorless crystals having a melting point of 165-166 ° C. (decomposition).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.68 (4H, m), 1.85-1.95 (2H, m), 2.18 (3H, s), 2.59 (2H, t, J = 7.3Hz), 2.79 -2.87 (4H, m), 2.98 (2H, t, J = 7Hz), 3.16 (2H, t, J = 8.3Hz), 3.77 (3H, s), 4.13 (2H, t, J = 8.3Hz), 6.89 (1H, t, J = 7.6Hz), 6.94 (1H, d, J = 7.6Hz), 7.15 (1H, d, J = 7.6Hz), 7.19 (1H, t, J = 7.6Hz), 7.81 ( 1H, s), 7.82 (1H, d, J = 8.3Hz), 8.08 (1H, d, J = 8.3Hz), 9.00 (2H, br.s).
IR (KBr) νcm ^-1 : 3436, 2945, 1676, 1661, 1602, 1492, 1438, 1399, 1334, 1243, 754.

参考例１６４で得た3-(2-メトキシフェニル)プロピル[5-(1-メチル-2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)-5-オキソペンチル]カルバミン酸 tert-ブチル(410mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(295mg) を融点88-89℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.57 (4H, br.s), 1.78-1.84 (2H, m), 2.47-2.53 (4H, m), 2.75-2.80 (4H, m), 2.85 (2H, t, J = 7Hz), 2.93 (2H, t, J = 7Hz), 3.19 (3H, s), 3.69 (3H, s), 6.79 (1H, t, J = 7.3Hz), 6.87 (1H, d, J = 7.3Hz), 7.07 (1H, d, J = 7.3Hz), 7.10 (1H, d, J = 8.3Hz), 7.11 (1H, t, J = 7.3Hz), 7.75 (1H, s), 7.81 (1H, d, J = 8.3Hz), 8.88 (2H, br.s).
IR (KBr) νcm^-1: 3434, 2948, 1672, 1603, 1495, 1464, 1360, 1245, 1128, 750. 6- (5-{[3- (2-Methoxyphenyl) propyl] amino} pentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one hydrochloride

3- (2-Methoxyphenyl) propyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl] carbamic acid obtained in Reference Example 164 The same operation as in Example 1 was carried out using tert-butyl (410 mg) to obtain the title compound (295 mg) as colorless crystals having a melting point of 88-89 ° C. (decomposition).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.57 (4H, br.s), 1.78-1.84 (2H, m), 2.47-2.53 (4H, m), 2.75-2.80 (4H, m), 2.85 ( 2H, t, J = 7Hz), 2.93 (2H, t, J = 7Hz), 3.19 (3H, s), 3.69 (3H, s), 6.79 (1H, t, J = 7.3Hz), 6.87 (1H, d, J = 7.3Hz), 7.07 (1H, d, J = 7.3Hz), 7.10 (1H, d, J = 8.3Hz), 7.11 (1H, t, J = 7.3Hz), 7.75 (1H, s) , 7.81 (1H, d, J = 8.3Hz), 8.88 (2H, br.s).
IR (KBr) νcm ^-1 : 3434, 2948, 1672, 1603, 1495, 1464, 1360, 1245, 1128, 750.

参考例１６５で得た5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル[3-(2-メトキシフェニル)プロピル]カルバミン酸 tert-ブチル(380mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(186mg) を淡黄色非晶状粉末として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.53-1.63 (4H, m), 1.77-1.85 (2H, m), 2.51 (2H, t, J = 7.5Hz), 2.76-2.81 (4H, m), 2.98 (2H, t, J = 6.6Hz), 3.26 (3H, s), 3.29 (3H, s), 3.69 (3H, s), 6.78 (1H, t, J = 7.3Hz), 6.87 (1H, d, J = 7.5Hz), 7.06 (1H, d, J = 7.5Hz), 7.10 (1H, t, J = 7.3Hz), 7.15 (1H, d, J = 8.3Hz), 7.62 (1H, d, J = 1.5Hz), 7.70 (1H, dd, J = 1.5, 8.3Hz), 8.92 (2H, br.s).
IR (KBr) νcm^-1: 3443, 2943, 1715, 1673, 1621, 1512, 1495, 1462, 1244, 1200, 758. 5- (5-{[3- (2-methoxyphenyl) propyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl [3- (2-methoxyphenyl) propyl] obtained in Reference Example 165 The same operation as in Example 1 was carried out using tert-butyl carbamate (380 mg) to obtain the title compound (186 mg) as a pale yellow amorphous powder.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.53-1.63 (4H, m), 1.77-1.85 (2H, m), 2.51 (2H, t, J = 7.5Hz), 2.76-2.81 (4H, m) , 2.98 (2H, t, J = 6.6Hz), 3.26 (3H, s), 3.29 (3H, s), 3.69 (3H, s), 6.78 (1H, t, J = 7.3Hz), 6.87 (1H, d, J = 7.5Hz), 7.06 (1H, d, J = 7.5Hz), 7.10 (1H, t, J = 7.3Hz), 7.15 (1H, d, J = 8.3Hz), 7.62 (1H, d, J = 1.5Hz), 7.70 (1H, dd, J = 1.5, 8.3Hz), 8.92 (2H, br.s).
IR (KBr) νcm ^-1 : 3443, 2943, 1715, 1673, 1621, 1512, 1495, 1462, 1244, 1200, 758.

参考例１６６で得た2-(2-エトキシフェノキシ)エチル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(205mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(152mg) を融点111-113℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.31 (3H, t, J = 6.6Hz), 1.69 (4H, br.s), 1.91 (2H, br.s), 2.76 (2H, br.s), 3.00-3.08 (4H, m), 3.29 (2H, br.s), 3.57 (2H, s), 3.60 (2H, br.s), 4.01 (2H, q, J = 6.6Hz), 4.26 (2H, br.s), 6.88-7.04 (4H, m), 7.71 (1H, s), 7.75 (1H, s), 9.16 (2H, br.s).
IR (KBr) νcm^-1: 3418, 2940, 1708, 1671, 1603, 1507, 1348, 1254, 1213, 1155, 1127, 740. 8- (5-{[2- (2-Ethoxyphenoxy) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

2- (2-Ethoxyphenoxy) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 166 -8-yl) pentyl] carbamate tert-butyl (205 mg) was used to give the title compound (152 mg) as colorless crystals with a melting point of 111-113 ° C. (decomposition) by the same procedure as in Example 1. It was.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.31 (3H, t, J = 6.6Hz), 1.69 (4H, br.s), 1.91 (2H, br.s), 2.76 (2H, br.s) , 3.00-3.08 (4H, m), 3.29 (2H, br.s), 3.57 (2H, s), 3.60 (2H, br.s), 4.01 (2H, q, J = 6.6Hz), 4.26 (2H , br.s), 6.88-7.04 (4H, m), 7.71 (1H, s), 7.75 (1H, s), 9.16 (2H, br.s).
IR (KBr) νcm ^-1 : 3418, 2940, 1708, 1671, 1603, 1507, 1348, 1254, 1213, 1155, 1127, 740.

参考例１６７で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-エトキシフェノキシ)エチル]カルバミン酸 tert-ブチル(390mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(275mg) を融点125-126℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.31 (3H, t, J = 6.8Hz), 1.65-1.71 (4H, m), 2.18 (3H, s), 2.99-3.18 (6H, m), 3.28 (2H, br.s), 4.01 (2H, q, J = 6.8Hz), 4.13 (2H, t, J = 8.3Hz), 4.28 (2H, t, J = 6Hz), 6.85-7.04 (4H, m), 7.81 (1H, s), 7.82 (1H, d, J = 8Hz), 8.08 (1H, d, J = 8Hz), 9.30 (2H, s).
IR (KBr) νcm^-1: 3498, 2943, 1683, 16424, 1598, 1509, 1488, 1448, 1407, 1254, 1209, 1126, 746. 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-{[2- (2-ethoxyphenoxy) ethyl] amino} pentan-1-one hydrochloride

Tert-Butyl (390 mg) of 5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-ethoxyphenoxy) ethyl] carbamate obtained in Reference Example 167 ) To give the title compound (275 mg) as colorless crystals with a melting point of 125-126 ° C. (decomposition) by the same procedure as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.31 (3H, t, J = 6.8Hz), 1.65-1.71 (4H, m), 2.18 (3H, s), 2.99-3.18 (6H, m), 3.28 (2H, br.s), 4.01 (2H, q, J = 6.8Hz), 4.13 (2H, t, J = 8.3Hz), 4.28 (2H, t, J = 6Hz), 6.85-7.04 (4H, m ), 7.81 (1H, s), 7.82 (1H, d, J = 8Hz), 8.08 (1H, d, J = 8Hz), 9.30 (2H, s).
IR (KBr) νcm ^-1 : 3498, 2943, 1683, 16424, 1598, 1509, 1488, 1448, 1407, 1254, 1209, 1126, 746.

参考例１６８で得た2-(2-エトキシフェノキシ)エチル[5-(1-メチル-2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)-5-オキソペンチル]カルバミン酸 tert-ブチル(420mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(292mg) を融点135-136℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.31 (3H, t, J = 6.8Hz), 1.65-1.76 (4H, m), 2.57 (2H, t, J = 6Hz), 2.93 (2H, t, J = 7Hz), 3.04 (2H, t, J = 7Hz), 3.09 (2H, br.s), 3.27 (3H, s), 3.29 (2H, t, J = 6Hz), 4.01 (2H, q, J = 6.8Hz), 4.28 (2H, t, J = 6Hz), 6.85-7.05 (4H, m), 7.18 (1H, d, J = 8.3Hz), 7.83 (1H, s), 7.89 (1H, d, J = 8.3Hz), 9.27 (2H, s).
IR (KBr) νcm^-1: 3436, 2954, 1671, 1605, 1508, 1455, 1358, 1256, 1220, 1130, 744. 6- (5-{[2- (2-Ethoxyphenoxy) ethyl] amino} pentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one hydrochloride

2- (2-Ethoxyphenoxy) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl] carbamic acid obtained in Reference Example 168 The same operation as in Example 1 was carried out using tert-butyl (420 mg) to obtain the title compound (292 mg) as colorless crystals having a melting point of 135 to 136 ° C. (decomposition).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.31 (3H, t, J = 6.8Hz), 1.65-1.76 (4H, m), 2.57 (2H, t, J = 6Hz), 2.93 (2H, t, J = 7Hz), 3.04 (2H, t, J = 7Hz), 3.09 (2H, br.s), 3.27 (3H, s), 3.29 (2H, t, J = 6Hz), 4.01 (2H, q, J = 6.8Hz), 4.28 (2H, t, J = 6Hz), 6.85-7.05 (4H, m), 7.18 (1H, d, J = 8.3Hz), 7.83 (1H, s), 7.89 (1H, d, J = 8.3Hz), 9.27 (2H, s).
IR (KBr) νcm ^-1 : 3436, 2954, 1671, 1605, 1508, 1455, 1358, 1256, 1220, 1130, 744.

参考例１６９で得た5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル[2-(2-エトキシフェノキシ)エチル]カルバミン酸 tert-ブチル(260mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(156mg) を融点103-105℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.31 (3H, t, J = 6.8Hz), 1.67-1.77 (4H, m), 3.09 (4H, t, J = 7Hz), 3.30 (2H, t, J = 7.5Hz), 3.36 (3H, s), 3.37 (3H, s), 4.00 (2H, q, J = 6.8Hz), 4.27 (2H, t, J = 5.3Hz), 6.85-7.00 (3H, m),7.03 (1H, dd, J = 1.7, 7.8Hz), 7.24 (1H, d, J = 8.3Hz), 7.72 (1H, d, J = 1.5Hz), 7.79 (1H, dd, J = 1.5, 8.3Hz), 9.23 (2H, br.s).
IR (KBr) νcm^-1: 3527, 2942, 2742, 1719, 1667, 1620, 1506, 1456, 1249, 1202, 1128, 737. 5- (5-{[2- (2-Ethoxyphenoxy) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

5- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl [2- (2-ethoxyphenoxy) ethyl] obtained in Reference Example 169 The title compound (156 mg) was obtained as colorless crystals with a melting point of 103-105 ° C. (decomposition) by carrying out the same operation as in Example 1 using tert-butyl carbamate (260 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.31 (3H, t, J = 6.8Hz), 1.67-1.77 (4H, m), 3.09 (4H, t, J = 7Hz), 3.30 (2H, t, J = 7.5Hz), 3.36 (3H, s), 3.37 (3H, s), 4.00 (2H, q, J = 6.8Hz), 4.27 (2H, t, J = 5.3Hz), 6.85-7.00 (3H, m), 7.03 (1H, dd, J = 1.7, 7.8Hz), 7.24 (1H, d, J = 8.3Hz), 7.72 (1H, d, J = 1.5Hz), 7.79 (1H, dd, J = 1.5 , 8.3Hz), 9.23 (2H, br.s).
IR (KBr) νcm ^-1 : 3527, 2942, 2742, 1719, 1667, 1620, 1506, 1456, 1249, 1202, 1128, 737.

参考例１７０で得た2-[(2-エトキシフェニル)アミノ]エチル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸 tert-ブチル(605mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(431mg) を融点98-100℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.36 (3H, t, J = 6.8Hz), 1.65-1.71 (4H, m), 1.88-1.94 (2H, m), 2.76 (2H, t, J = 6.0Hz), 2.94-3.00 (4H, m), 3.11 (2H, br.s), 3.51 (2H, t, J = 6.6Hz), 3.57 (2H, s), 3.60 (2H, t, J = 6.0Hz), 4.04 (2H, q, J = 6.8Hz), 6.26 (2H, br) 6.80-6.86 (2H, m), 6.91-6.93 (2H, m), 7.71 (1H, s), 7.75 (1H, s), 9.27 (2H, s).
IR (KBr) νcm^-1: 3392, 2774, 1709, 1665, 1606, 1496, 1344, 1267, 1162, 1040, 766. 8- [5-({2-[(2-Ethoxyphenyl) amino] ethyl} amino) pentanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H)- ON dihydrochloride

2-[(2-Ethoxyphenyl) amino] ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-8-yl) pentyl] carbamic acid tert-butyl (605 mg) was used in the same manner as in Example 1 to give the title compound (431 mg) as a colorless compound having a melting point of 98-100 ° C. (decomposition). Obtained as crystals.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.36 (3H, t, J = 6.8Hz), 1.65-1.71 (4H, m), 1.88-1.94 (2H, m), 2.76 (2H, t, J = 6.0Hz), 2.94-3.00 (4H, m), 3.11 (2H, br.s), 3.51 (2H, t, J = 6.6Hz), 3.57 (2H, s), 3.60 (2H, t, J = 6.0 Hz), 4.04 (2H, q, J = 6.8Hz), 6.26 (2H, br) 6.80-6.86 (2H, m), 6.91-6.93 (2H, m), 7.71 (1H, s), 7.75 (1H, s), 9.27 (2H, s).
IR (KBr) νcm ^-1 : 3392, 2774, 1709, 1665, 1606, 1496, 1344, 1267, 1162, 1040, 766.

参考例１７１で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル{2-[(2-エトキシフェニル)アミノ]エチル}カルバミン酸 tert-ブチル(690mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(545mg) を融点155-157℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.36 (3H, t, J = 6.8Hz), 1.64-1.70 (4H, m), 2.18 (3H, s), 2.95 (2H, br.s), 3.00 (2H, t, J = 6.8Hz), 3.13-3.19 (4H, m), 3.53 (2H, t, J = 6.6Hz), 4.05 (2H, q, J = 6.8Hz), 4.14 (2H, t, J = 8.5Hz), 6.85-7.02 (4H, m), 6.94 (2H, br) 7.82 (1H, s), 7.83 (1H, d, J = 8.3Hz), 8.07 (1H, d, J = 8.3Hz), 9.36 (2H, s).
IR (KBr) νcm^-1: 3546, 3467, 2748, 1678, 1600, 1504, 1439, 1393, 1322, 1265, 1122, 1042, 762. 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-({2-[(2-ethoxyphenyl) amino] ethyl} amino) pentan-1-one dihydrochloride

5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl {2-[(2-ethoxyphenyl) amino] ethyl} carbamic acid tert- obtained in Reference Example 171 The same operation as in Example 1 was carried out using butyl (690 mg) to give the title compound (545 mg) as colorless crystals having a melting point of 155-157 ° C. (decomposition).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.36 (3H, t, J = 6.8Hz), 1.64-1.70 (4H, m), 2.18 (3H, s), 2.95 (2H, br.s), 3.00 (2H, t, J = 6.8Hz), 3.13-3.19 (4H, m), 3.53 (2H, t, J = 6.6Hz), 4.05 (2H, q, J = 6.8Hz), 4.14 (2H, t, J = 8.5Hz), 6.85-7.02 (4H, m), 6.94 (2H, br) 7.82 (1H, s), 7.83 (1H, d, J = 8.3Hz), 8.07 (1H, d, J = 8.3Hz ), 9.36 (2H, s).
IR (KBr) νcm ^-1 : 3546, 3467, 2748, 1678, 1600, 1504, 1439, 1393, 1322, 1265, 1122, 1042, 762.

参考例１７１で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル{2-[(2-エトキシフェニル)アミノ]エチル}カルバミン酸 tert-ブチル(660mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(448mg) を融点173-175℃(分解)の無色結晶として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.36 (3H, t, J = 7.0Hz), 1.65-1.73 (4H, m), 2.97 (2H, br.s), 3.08 (2H, t, J = 6.8Hz), 3.13 (2H, br.s), 3.35 (3H, s), 3.37 (3H, s), 3.53 (2H, t, J = 6.5Hz), 4.05 (2H, q, J = 7.0Hz), 6.85-7.02 (4H, m), 7.24 (1H, d, J = 8.3Hz), 7.46 (2H, br) 7.72 (1H, s), 7.79 (1H, d, J = 8.3Hz), 9.39 (2H, s).
IR (KBr) νcm^-1: 3423, 2749, 1718, 1673, 1619, 1506, 1394, 1263, 1200, 1041, 767. 5- [5-({2-[(2-Ethoxyphenyl) amino] ethyl} amino) pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one dihydrochloride

5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl {2-[(2-ethoxyphenyl) amino] ethyl} carbamic acid tert- obtained in Reference Example 171 The same operation as in Example 1 was carried out using butyl (660 mg) to obtain the title compound (448 mg) as colorless crystals having a melting point of 173-175 ° C. (decomposition).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.36 (3H, t, J = 7.0Hz), 1.65-1.73 (4H, m), 2.97 (2H, br.s), 3.08 (2H, t, J = 6.8Hz), 3.13 (2H, br.s), 3.35 (3H, s), 3.37 (3H, s), 3.53 (2H, t, J = 6.5Hz), 4.05 (2H, q, J = 7.0Hz) , 6.85-7.02 (4H, m), 7.24 (1H, d, J = 8.3Hz), 7.46 (2H, br) 7.72 (1H, s), 7.79 (1H, d, J = 8.3Hz), 9.39 (2H , s).
IR (KBr) νcm ^-1 : 3423, 2749, 1718, 1673, 1619, 1506, 1394, 1263, 1200, 1041, 767.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(312mg)、および(2-ブロモエチル)ベンゼン(185mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物を融点207-208℃の淡黄色結晶(285mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.42-1.47 (3H, m), 1.69-1.80 (4H, m), 2.01-2.13 (4H, m), 2.64-2.68 (2H, m), 2.81-2.88 (4H, m), 2.95 (2H, t, J = 7.6Hz), 3.10 (2H, d, J = 11.5Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.18-7.30 (5H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1715, 1672, 1604, 1343, 1152. 8- {3- [1- (2-Phenylethyl) -4-piperidinyl] propanoyl} -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- [3- (4-piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (312 mg) obtained in Reference Example 174, and The title compound was obtained as pale-yellow crystals (285 mg) having a melting point of 207-208 ° C. by carrying out the same operation as in Example 81 using (2-bromoethyl) benzene (185 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.42-1.47 (3H, m), 1.69-1.80 (4H, m), 2.01-2.13 (4H, m), 2.64-2.68 (2H, m), 2.81 -2.88 (4H, m), 2.95 (2H, t, J = 7.6Hz), 3.10 (2H, d, J = 11.5Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.18-7.30 (5H, m), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1715, 1672, 1604, 1343, 1152.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(312mg)、およびメタンスルホン酸2-(2-メトキシフェニル)エチル(230mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末(184mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.67-1.76 (4H, m), 1.97-2.07 (4H, m), 2.51-2.55 (2H, m), 2.80-2.84 (4H, m), 2.94 (2H, t, J = 7.5Hz), 3.03 (2H, d, J = 11.0Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 3.81(3H, s), 6.83-6.89 (2H, m), 7.13-7.20 (2H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1717, 1673, 1604, 1495, 1343, 1243, 1153. 8- (3- {1- [2- (2-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H ) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (312 mg) obtained in Reference Example 174, and The title compound was obtained as a pale-yellow amorphous powder (184 mg) by the same procedures as in Example 81 using 2- (2-methoxyphenyl) ethyl methanesulfonate (230 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.67-1.76 (4H, m), 1.97-2.07 (4H, m), 2.51-2.55 (2H, m), 2.80 -2.84 (4H, m), 2.94 (2H, t, J = 7.5Hz), 3.03 (2H, d, J = 11.0Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 3.81 (3H, s), 6.83-6.89 (2H, m), 7.13-7.20 (2H, m), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1717, 1673, 1604, 1495, 1343, 1243, 1153.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、およびメタンスルホン酸2-(2-メチルフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 1.99-2.07 (4H, m), 2.32 (3H, s), 2.49-2.53 (2H, m), 2.79-2.85 (4H, m), 2.95 (2H, t, J = 7.5Hz), 3.06 (2H, d, J = 10.7Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.09-7.15 (4H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1717, 1673, 1604, 1495, 1342, 1153. 8- (3- {1- [2- (2-methylphenyl) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H ) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and methanesulfonic acid The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 81 using 2- (2-methylphenyl) ethyl.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 1.99-2.07 (4H, m), 2.32 (3H, s), 2.49-2.53 (2H, m), 2.79-2.85 (4H, m), 2.95 (2H, t, J = 7.5Hz), 3.06 (2H, d, J = 10.7Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.09-7.15 (4H, m), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1717, 1673, 1604, 1495, 1342, 1153.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、およびメタンスルホン酸2-(2-クロロフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 2.01-2.07 (4H, m), 2.55-2.59 (2H, m), 2.82 (2H, t, J = 6Hz), 2.93-2.96 (4H, m), 3.03 (2H, d, J = 11.0Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.13-7.34 (4H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1716, 1673, 1604, 1496, 1342, 1152. 8- (3- {1- [2- (2-chlorophenyl) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and methanesulfonic acid The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 81 using 2- (2-chlorophenyl) ethyl.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 2.01-2.07 (4H, m), 2.55-2.59 (2H, m), 2.82 (2H, t, J = 6Hz), 2.93-2.96 (4H, m), 3.03 (2H, d, J = 11.0Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.13 -7.34 (4H, m), 7.73 (2H, s).
^{IR (KBr) νcm -1: 1716} , 1673, 1604, 1496, 1342, 1152.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、およびメタンスルホン酸2-(3-メトキシフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.39 (3H, m), 1.68-1.77 (4H, m), 1.97-2.07 (4H, m), 2.55-2.59 (2H, m), 2.77-2.84 (4H, m), 2.93-3.02 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 3.79 (3H, s), 6.73-6.80 (3H, m), 7.20 (1H, t, J = 8Hz), 7.73 (2H, s).
IR (KBr) νcm^-1: 1717, 1673, 1603, 1342, 1152. 8- (3- {1- [2- (3-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H ) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and methanesulfonic acid The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 81 using 2- (3-methoxyphenyl) ethyl.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.39 (3H, m), 1.68-1.77 (4H, m), 1.97-2.07 (4H, m), 2.55-2.59 (2H, m), 2.77 -2.84 (4H, m), 2.93-3.02 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 3.79 (3H, s), 6.73-6.80 (3H, m) , 7.20 (1H, t, J = 8Hz), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1717, 1673, 1603, 1342, 1152.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、およびメタンスルホン酸2-(3-メチルフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.39 (3H, m), 1.68-1.77 (4H, m), 1.97-2.07 (4H, m), 2.32 (3H, s), 2.54-2.58 (2H, m), 2.75-2.85 (4H, m), 2.93-3.03 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 6.99-7.04 (3H, m), 7.17 (1H, t, J = 8Hz), 7.73 (2H, s).
IR (KBr) νcm^-1: 1719, 1673, 1605, 1342, 1152. 8- (3- {1- [2- (3-methylphenyl) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H ) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and methanesulfonic acid The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 81 using 2- (3-methylphenyl) ethyl.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.39 (3H, m), 1.68-1.77 (4H, m), 1.97-2.07 (4H, m), 2.32 (3H, s), 2.54-2.58 (2H, m), 2.75-2.85 (4H, m), 2.93-3.03 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 6.99-7.04 (3H, m) , 7.17 (1H, t, J = 8Hz), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1719, 1673, 1605, 1342, 1152.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン(312mg)、およびメタンスルホン酸2-(3-クロロフェニル)エチル(235mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物を融点108-109℃の淡黄色結晶(200mg) として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.28-1.40 (3H, m), 1.67-1.77 (4H, m), 1.96-2.07 (4H, m), 2.53-2.57 (2H, m), 2.76-2.84 (4H, m), 2.90-3.00 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.07-7.25 (4H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1717, 1673, 1603, 1343, 1152. 8- (3- {1- [2- (3-chlorophenyl) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one (312 mg) obtained in Reference Example 174, and The title compound was obtained as pale-yellow crystals (200 mg) with a melting point of 108-109 ° C. by the same procedure as in Example 81 using 2- (3-chlorophenyl) ethyl methanesulfonate (235 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.28-1.40 (3H, m), 1.67-1.77 (4H, m), 1.96-2.07 (4H, m), 2.53-2.57 (2H, m), 2.76 -2.84 (4H, m), 2.90-3.00 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.07-7.25 (4H, m), 7.73 (2H, s) .
IR (KBr) νcm ^-1 : 1717, 1673, 1603, 1343, 1152.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、およびメタンスルホン酸2-(3-フルオロフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を融点214-215℃の淡黄色結晶として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.29-1.40 (3H, m), 1.68-1.77 (4H, m), 1.97-2.07 (4H, m), 2.54-2.58 (2H, m), 2.78-2.84 (4H, m), 2.93-3.00 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 6.86-6.98 (3H, m), 7.20-7.26 (1H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1717, 1673, 1604, 1342, 1143. 8- (3- {1- [2- (3-Fluorophenyl) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H ) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and methanesulfonic acid The title compound was obtained as pale-yellow crystals with a melting point of 214-215 ° C. by the same procedure as in Example 81 using 2- (3-fluorophenyl) ethyl.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.29-1.40 (3H, m), 1.68-1.77 (4H, m), 1.97-2.07 (4H, m), 2.54-2.58 (2H, m), 2.78 -2.84 (4H, m), 2.93-3.00 (4H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 6.86-6.98 (3H, m), 7.20-7.26 (1H, m), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1717, 1673, 1604, 1342, 1143.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、および(3-ブロモプロピル)ベンゼンを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.25-1.40 (3H, m), 1.63-1.73 (4H, m), 1.80-1.92 (5H, m), 2.00-2.06 (2H, m), 2.35 (2H, t, J = 7.6Hz), 2.62 (2H, t, J = 7.6Hz), 2.82 (2H, t, J = 6Hz),2.91-2.95 (3H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.12-7.33 (5H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1714, 1672, 1604, 1496, 1344, 1153. 8- {3- [1- (3-Phenylpropyl) -4-piperidinyl] propanoyl} -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and (3- The title compound was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 81 using bromopropyl) benzene.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.25-1.40 (3H, m), 1.63-1.73 (4H, m), 1.80-1.92 (5H, m), 2.00-2.06 (2H, m), 2.35 (2H, t, J = 7.6Hz), 2.62 (2H, t, J = 7.6Hz), 2.82 (2H, t, J = 6Hz), 2.91-2.95 (3H, m), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 7.12-7.33 (5H, m), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1714, 1672, 1604, 1496, 1344, 1153.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、および1-(2-ブロモエトキシ)-2-メチルベンゼンを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.35 (3H, m), 1.67-1.75 (4H, m), 2.00-2.06 (2H, m), 2.14 (2H, t, J = 11.0Hz), 2.21 (3H, s), 2.80-2.84 (4H, m), 2.94 (2H, t, J = 7.4Hz), 3.03 (2H, d, J = 11Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 4.11 (2H, t, J = 6Hz), 6.80-6.87 (2H, m), 7.12-7.15 (2H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1718, 1673, 1604, 1496, 1343, 1244. 8- (3- {1- [2- (2-methylphenoxy) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H ) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and 1- ( The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 81 using 2-bromoethoxy) -2-methylbenzene.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.35 (3H, m), 1.67-1.75 (4H, m), 2.00-2.06 (2H, m), 2.14 (2H, t, J = 11.0 Hz ), 2.21 (3H, s), 2.80-2.84 (4H, m), 2.94 (2H, t, J = 7.4Hz), 3.03 (2H, d, J = 11Hz), 3.55 (2H, s), 3.74 ( 2H, t, J = 6Hz), 4.11 (2H, t, J = 6Hz), 6.80-6.87 (2H, m), 7.12-7.15 (2H, m), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1718, 1673, 1604, 1496, 1343, 1244.

参考例１７４で得た8-[3-(4-ピペリジニル)プロパノイル]-5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン-2(1H)-オン、および1-(2-ブロモエトキシ)-2-エトキシベンゼンを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.39 (3H, m), 1.43 (3H, t, J = 7Hz), 1.67-1.75 (4H, m), 2.00-2.13 (4H, m), 2.81-2.84 (4H, m), 2.94 (2H, t, J = 7.5Hz), 3.03 (2H, d, J = 11Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz), 4.07(2H, q, J = 7Hz), 4.11-4.15 (2H, m), 6.87-6.91 (4H, m), 7.73 (2H, s).
IR (KBr) νcm^-1: 1717, 1672, 1604, 1499, 1342, 1253. 8- (3- {1- [2- (2-Ethoxyphenoxy) ethyl] -4-piperidinyl} propanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H ) -On hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one obtained in Reference Example 174, and 1- ( The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 81 using 2-bromoethoxy) -2-ethoxybenzene.
¹ H NMR (free base; 400MHz, CDCl ₃ ) δ 1.30-1.39 (3H, m), 1.43 (3H, t, J = 7Hz), 1.67-1.75 (4H, m), 2.00-2.13 (4H, m) , 2.81-2.84 (4H, m), 2.94 (2H, t, J = 7.5Hz), 3.03 (2H, d, J = 11Hz), 3.55 (2H, s), 3.74 (2H, t, J = 6Hz) , 4.07 (2H, q, J = 7Hz), 4.11-4.15 (2H, m), 6.87-6.91 (4H, m), 7.73 (2H, s).
IR (KBr) νcm ^-1 : 1717, 1672, 1604, 1499, 1342, 1253.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、および(2-ブロモエチル)ベンゼンを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.68-1.77 (4H, m), 1.94-2.03 (4H, m), 2.56-2.69 (2H, m), 2.68 (2H, t, J = 7Hz), 2.79-2.86 (4H, m), 2.94 (4H, t, J = 7Hz), 3.02 (2H, d, J = 11Hz),), 3.90 (2H, t, J = 6Hz), 7.17-7.30 (5H, m), 7.62 (2H, d, J = 5.4Hz).
IR (KBr) νcm^-1: 1674, 1604, 1360, 1158. 9- {3- [1- (2-Phenylethyl) -4-piperidinyl] propanoyl} -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5- On hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by performing the same operation as in Example 81 using (2-bromoethyl) benzene.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.68-1.77 (4H, m), 1.94-2.03 (4H, m), 2.56-2.69 (2H, m), 2.68 (2H, t, J = 7Hz), 2.79-2.86 (4H, m), 2.94 (4H, t, J = 7Hz), 3.02 (2H, d, J = 11Hz),), 3.90 (2H, t, J = 6Hz), 7.17-7.30 (5H, m), 7.62 (2H, d, J = 5.4Hz).
IR (KBr) νcm ^-1 : 1674, 1604, 1360, 1158.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、およびメタンスルホン酸2-(2-メトキシフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.67-1.76 (4H, m), 1.94-2.03 (4H, m), 2.51-2.55 (2H, m), 2.68 (2H, t, J = 7Hz), 2.81-2.86 (4H, m), 2.94 (4H, t, J = 7Hz), 3.03 (2H, d, J = 11Hz), 3.81 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.13-7.20 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1674, 1604, 1494, 1362, 1339, 1243, 1168. 9- (3- {1- [2- (2-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij ] Quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by the same operation as in Example 81 using 2- (2-methoxyphenyl) ethyl methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.67-1.76 (4H, m), 1.94-2.03 (4H, m), 2.51-2.55 (2H, m), 2.68 (2H, t, J = 7Hz), 2.81-2.86 (4H, m), 2.94 (4H, t, J = 7Hz), 3.03 (2H, d, J = 11Hz), 3.81 (3H, s), 3.89 ( 2H, t, J = 6Hz), 6.83-6.89 (2H, m), 7.13-7.20 (2H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1674, 1604, 1494, 1362, 1339, 1243, 1168.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、およびメタンスルホン酸2-(2-メトキシフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 1.94-2.07 (4H, m), 2.55-2.59 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.96 (6H, t, J = 7Hz), 3.03 (2H, d, J = 11Hz), 3.89(2H, d, J = 6Hz), 7.12-7.34 (4H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1674, 1604, 1489, 1361, 1339, 1168. 9- (3- {1- [2- (2-chlorophenyl) ethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] Quinoline-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by the same operation as in Example 81 using 2- (2-methoxyphenyl) ethyl methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 1.94-2.07 (4H, m), 2.55-2.59 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.96 (6H, t, J = 7Hz), 3.03 (2H, d, J = 11Hz), 3.89 (2H, d, J = 6Hz), 7.12-7.34 (4H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1674, 1604, 1489, 1361, 1339, 1168.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、およびメタンスルホン酸2-(3-メトキシフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.67-1.77 (4H, m), 1.95-2.02 (4H, m), 2.53-2.60 (2H, m), 2.68 (2H, t, J = 7Hz), 2.77-2.87 (4H, m), 2.92-3.02 (6H, m), 3.79 (3H, s), 3.89 (2H, t, J = 6Hz), 6.73-6.80 (3H, m), 7.18-7.22 (1H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1674, 1603, 1485, 1361, 1339, 1167. 9- (3- {1- [2- (3-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij ] Quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by the same procedure as in Example 81 using 2- (3-methoxyphenyl) ethyl methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.67-1.77 (4H, m), 1.95-2.02 (4H, m), 2.53-2.60 (2H, m), 2.68 (2H, t, J = 7Hz), 2.77-2.87 (4H, m), 2.92-3.02 (6H, m), 3.79 (3H, s), 3.89 (2H, t, J = 6Hz), 6.73-6.80 ( 3H, m), 7.18-7.22 (1H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1674, 1603, 1485, 1361, 1339, 1167.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、およびメタンスルホン酸2-(3-メチルフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.70-1.77 (4H, m), 1.94-2.02 (4H, m), 2.32 (3H, s), 2.54-2.58 (2H, m), 2.68 (2H, t, J = 7Hz), 2.75-2.80 (2H, m), 2.83-2.86 (2H, m), 2.94 (4H, t, J = 7Hz), 3.02 (2H, d, J = 11Hz), 3.89 (2H, t, J = 6Hz), 6.99-7.01 (3H, m), 7.17 (1H, t, J = 7Hz), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1675, 1604, 1485, 1361, 1339, 1166. 9- (3- {1- [2- (3-methylphenyl) ethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij ] Quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by the same procedure as in Example 81 using 2- (3-methylphenyl) ethyl methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.70-1.77 (4H, m), 1.94-2.02 (4H, m), 2.32 (3H, s), 2.54-2.58 (2H, m), 2.68 (2H, t, J = 7Hz), 2.75-2.80 (2H, m), 2.83-2.86 (2H, m), 2.94 (4H, t, J = 7Hz), 3.02 (2H, d, J = 11Hz), 3.89 (2H, t, J = 6Hz), 6.99-7.01 (3H, m), 7.17 (1H, t, J = 7Hz), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1675, 1604, 1485, 1361, 1339, 1166.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、およびメタンスルホン酸2-(3-クロロフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.68-1.77 (4H, m), 1.94-2.02 (4H, m), 2.54-2.58 (2H, m), 2.68 (2H, t, J = 7Hz), 2.76-2.80 (2H, m), 2.84 (2H, t, J = 6Hz), 2.90-3.00 (6H, m), 3.90 (2H, t, J = 6Hz), 7.08 (1H, d, J = 7Hz), 7.16-7.23 (3H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1674, 1603, 1483, 1360, 1338, 1167. 9- (3- {1- [2- (3-chlorophenyl) ethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] Quinoline-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by the same procedure as in Example 81 using 2- (3-chlorophenyl) ethyl methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.68-1.77 (4H, m), 1.94-2.02 (4H, m), 2.54-2.58 (2H, m), 2.68 (2H, t, J = 7Hz), 2.76-2.80 (2H, m), 2.84 (2H, t, J = 6Hz), 2.90-3.00 (6H, m), 3.90 (2H, t, J = 6Hz), 7.08 (1H, d, J = 7Hz), 7.16-7.23 (3H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1674, 1603, 1483, 1360, 1338, 1167.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、およびメタンスルホン酸2-(3-フルオロフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.68-1.81 (4H, m), 1.94-2.02 (4H, m), 2.55-2.59 (2H, m), 2.68 (2H, t, J = 7Hz), 2.78-2.86 (4H, m), 2.92-3.00 (6H, m), 3.89 (2H, t, J = 6Hz), 6.86-6.98 (3H, m), 7.23 (1H, q, J = 4Hz), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1674, 1604, 1585, 1486, 1361, 1339, 1158. 9- (3- {1- [2- (3-Fluorophenyl) ethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij ] Quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by the same operation as in Example 81 using 2- (3-fluorophenyl) ethyl methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.68-1.81 (4H, m), 1.94-2.02 (4H, m), 2.55-2.59 (2H, m), 2.68 (2H, t, J = 7Hz), 2.78-2.86 (4H, m), 2.92-3.00 (6H, m), 3.89 (2H, t, J = 6Hz), 6.86-6.98 (3H, m), 7.23 ( 1H, q, J = 4Hz), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1674, 1604, 1585, 1486, 1361, 1339, 1158.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、および(±)-メタンスルホン酸1-メチル-2-フェニルエチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 0.94 (3H, d, J = 6Hz), 1.30-1.40 (3H, m), 1.67-1.78 (4H, m), 1.94-2.00 (2H, m), 2.26-2.42 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz),2.90-3.04 (9H, m), 3.90 (2H, t, J = 6Hz), 7.16-7.34 (5H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1673, 1604, 1484, 1361, 1339, 1158. (±) -9- {3- [1- (1-Methyl-2-phenylethyl) -4-piperidinyl] propanoyl} -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2, 1-ij] quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by conducting the same operation as in Example 81 using 1-methyl-2-phenylethyl (±) -methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 0.94 (3H, d, J = 6 Hz), 1.30-1.40 (3H, m), 1.67-1.78 (4H, m), 1.94-2.00 (2H, m) , 2.26-2.42 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.90-3.04 (9H, m), 3.90 (2H, t, J = 6Hz ), 7.16-7.34 (5H, m), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1673, 1604, 1484, 1361, 1339, 1158.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、および(±)-メタンスルホン酸2-(2-メトキシフェニル)-1-メチルエチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 0.94 (3H, d, J = 6Hz), 1.30-1.40 (3H, m), 1.67-1.77 (4H, m), 1.94-2.00 (2H, m), 2.36-2.44 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz),2.92-3.04 (9H, m), 3.80 (3H, s), 3.89 (2H, t, J = 6Hz), 6.83 (1H, d, J = 7Hz), 6.88 (1H, t, J = 6Hz), 7.10 (1H, d, J = 7Hz), 7.17 (1H, t, J = 6Hz), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1675, 1604, 1494, 1362, 1339, 1244, 1159. (±) -9- (3- {1- [2- (2-methoxyphenyl) -1-methylethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by the same procedure as in Example 81 using 2- (2-methoxyphenyl) -1-methylethyl (±) -methanesulfonate.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 0.94 (3H, d, J = 6 Hz), 1.30-1.40 (3H, m), 1.67-1.77 (4H, m), 1.94-2.00 (2H, m) , 2.36-2.44 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.92-3.04 (9H, m), 3.80 (3H, s), 3.89 ( 2H, t, J = 6Hz), 6.83 (1H, d, J = 7Hz), 6.88 (1H, t, J = 6Hz), 7.10 (1H, d, J = 7Hz), 7.17 (1H, t, J = 6Hz), 7.62 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1675, 1604, 1494, 1362, 1339, 1244, 1159.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、および(3-ブロモプロピル)ベンゼンを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.28-1.40 (3H, m), 1.67-1.73 (4H, m), 1.79-1.91 (4H, m), 1.93-2.04 (2H, m), 2.35 (2H, t, J = 7.5Hz), 2.60-2.70 (4H, m), 2.84 (2H, t, J = 6Hz), 2.90-2.95 (6H, m), 3.89 (2H, t, J = 6Hz), 7.15-7.29 (5H, m), 7.61 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1675, 1604, 1361, 1339, 1166. 9- {3- [1- (3-Phenylpropyl) -4-piperidinyl] propanoyl} -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline-5- On hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The title compound was obtained as a pale-yellow amorphous powder by performing the same operation as in Example 81 using (3-bromopropyl) benzene.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.28-1.40 (3H, m), 1.67-1.73 (4H, m), 1.79-1.91 (4H, m), 1.93-2.04 (2H, m), 2.35 (2H, t, J = 7.5Hz), 2.60-2.70 (4H, m), 2.84 (2H, t, J = 6Hz), 2.90-2.95 (6H, m), 3.89 (2H, t, J = 6Hz) , 7.15-7.29 (5H, m), 7.61 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1675, 1604, 1361, 1339, 1166.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、および(±)-(2-ブロモプロポキシ)ベンゼンを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.19 (3H, d, J = 6Hz), 1.30-1.40 (3H, m), 1.66-1.76 (4H, m), 1.93-1.99 (2H, m), 2.28-2.40 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.91-3.04 (7H, m), 3.89 (2H, d, J = 6Hz), 4.05-4.10 (2H, m), 6.88-6.95 (3H, m), 7.25-7.30 (2H, m), 7.61 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1674, 1601, 1496, 1361, 1339, 1244, 1159. (±) -9- {3- [1- (1-Methyl-2-phenoxyethyl) -4-piperidinyl] propanoyl} -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2, 1-ij] quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The same operation as in Example 81 was performed using (±)-(2-bromopropoxy) benzene to obtain the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.19 (3H, d, J = 6 Hz), 1.30-1.40 (3H, m), 1.66-1.76 (4H, m), 1.93-1.99 (2H, m) , 2.28-2.40 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.91-3.04 (7H, m), 3.89 (2H, d, J = 6Hz ), 4.05-4.10 (2H, m), 6.88-6.95 (3H, m), 7.25-7.30 (2H, m), 7.61 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1674, 1601, 1496, 1361, 1339, 1244, 1159.

参考例１７６で得た9-[3-(4-ピペリジニル)プロパノイル]-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン、および(±)-1-(2-ブロモプロポキシ)-2-メトキシベンゼンを用いて、実施例８１と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.18 (3H, d, J = 6Hz), 1.30-1.40 (3H, m), 1.66-1.75 (4H, m), 1.94-2.00 (2H, m), 2.23-2.39 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.90-2.96 (6H, m), 3.07-3.11 (1H, m), 3.85 (3H, s), 3.89 (2H, d, J = 6Hz), 4.11-4.16 (2H, m), 6.88-6.94 (4H, m), 7.61 (2H, d, J = 5Hz).
IR (KBr) νcm^-1: 1673, 1601, 1506, 1362, 1338, 1253, 1158. (±) -9- (3- {1- [2- (2-methoxyphenoxy) -1-methylethyl] -4-piperidinyl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one hydrochloride

9- [3- (4-Piperidinyl) propanoyl] -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176, and The same operation as in Example 81 was performed using (±) -1- (2-bromopropoxy) -2-methoxybenzene to give the title compound as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.18 (3H, d, J = 6 Hz), 1.30-1.40 (3H, m), 1.66-1.75 (4H, m), 1.94-2.00 (2H, m) , 2.23-2.39 (2H, m), 2.68 (2H, t, J = 7Hz), 2.84 (2H, t, J = 6Hz), 2.90-2.96 (6H, m), 3.07-3.11 (1H, m), 3.85 (3H, s), 3.89 (2H, d, J = 6Hz), 4.11-4.16 (2H, m), 6.88-6.94 (4H, m), 7.61 (2H, d, J = 5Hz).
IR (KBr) νcm ^-1 : 1673, 1601, 1506, 1362, 1338, 1253, 1158.

参考例１７７で得た6-(5-クロロペンタノイル)-3,4-ジヒドロ-2(1H)-キナゾリノンおよび2-フェニルエチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点199-205℃(分解)の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.68-1.66 (4H, m), 2.99-2.94 (6H, m), 3.10 (2H, m), 4.38 (2H, s), 6.86 (1H, d, J = 9.0Hz), 7.04 (1H,s), 7.28-7.25 (3H, m), 7.34-7.32 (2H, m), 7.80-7.76 (2H, m), 9.02 (2H, s), 9.47 (1H, br.s).
元素分析 C₂₁H₂₅N₃O₂・HClとして
計算値：C, 65.02; H, 6.76; N, 10.83.
実験値：C, 64.42; H, 6.58; N, 10.80.
MS m/z: 352 [M+H]⁺ 6- {5-[(2-Phenylethyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Using 6- (5-chloropentanoyl) -3,4-dihydro-2 (1H) -quinazolinone and 2-phenylethylamine obtained in Reference Example 177, operations similar to Reference Example 19 and Example 1 were sequentially performed. This gave the title compound as colorless crystals having a melting point of 199-205 ° C. (decomposition).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.68-1.66 (4H, m), 2.99-2.94 (6H, m), 3.10 (2H, m), 4.38 (2H, s), 6.86 (1H, d, J = 9.0Hz), 7.04 (1H, s), 7.28-7.25 (3H, m), 7.34-7.32 (2H, m), 7.80-7.76 (2H, m), 9.02 (2H, s), 9.47 (1H , br.s).
Elemental analysis Calculated as C ₂₁ H ₂₅ N ₃ O ₂ .HCl: C, 65.02; H, 6.76; N, 10.83.
Experimental value: C, 64.42; H, 6.58; N, 10.80.
MS m / z: 352 [M + H] ⁺

参考例１７７で得た6-(5-クロロペンタノイル)-3,4-ジヒドロ-2(1H)-キナゾリノンおよび2-(2-メトキシフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点176-180℃(分解)の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.66 (4H, m), 3.03-2.95 (8H, m), 3.79 (3H, s), 4.37 (2H, s), 7.01-6.83 (4H, m), 7.27-7.16 (2H, m), 7.78-7.75 (2H, m), 8.87 (2H, br.s), 9.44 (1H, s).
元素分析 C₂₂H₂₇N₃O₃・HCl・H₂O として
計算値：C, 63.22; H, 6.75; N, 10.05.
実験値：C, 62.98; H, 6.62; N, 10.11.
MS m/z: 382 [M+H]⁺ 6- (5-{[2- (2-Methoxyphenyl) ethyl] amino} pentanoyl) -3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Using Reference Example 19 and Example 1 with 6- (5-chloropentanoyl) -3,4-dihydro-2 (1H) -quinazolinone and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 177 By sequentially carrying out the same operation, the title compound was obtained as colorless crystals having a melting point of 176-180 ° C. (decomposition).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.66 (4H, m), 3.03-2.95 (8H, m), 3.79 (3H, s), 4.37 (2H, s), 7.01-6.83 (4H, m) , 7.27-7.16 (2H, m), 7.78-7.75 (2H, m), 8.87 (2H, br.s), 9.44 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₂₇ N ₃ O ₃ .HCl.H ₂ O: C, 63.22; H, 6.75; N, 10.05.
Experimental value: C, 62.98; H, 6.62; N, 10.11.
MS m / z: 382 [M + H] ⁺

参考例１７７で得た6-(5-クロロペンタノイル)-3,4-ジヒドロ-2(1H)-キナゾリノンおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点176-185℃(分解)の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.68 (4H, m), 3.11-2.96 (8H, m), 4.39 (2H, s), 6.86 (1H, d, J = 8.1Hz), 7.04 (1H, s), 7.49-7.28 (4H, m), 7.81-7.77 (2H, m), 9.17 (2H, br.s), 9.47 (1H, s).
元素分析 C₂₁H₂₄N₃O₂・HClとして
計算値：C, 59.72; H, 5.97; N, 9.95.
実験値：C, 59.43; H, 5.69; N, 9.51.
MS m/z: 386 [M+H]⁺ 6- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Similar to Reference Example 19 and Example 1 using 6- (5-chloropentanoyl) -3,4-dihydro-2 (1H) -quinazolinone and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 177 By sequentially performing the above operations, the title compound was obtained as colorless crystals having a melting point of 176-185 ° C. (decomposition).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.68 (4H, m), 3.11-2.96 (8H, m), 4.39 (2H, s), 6.86 (1H, d, J = 8.1Hz), 7.04 (1H , s), 7.49-7.28 (4H, m), 7.81-7.77 (2H, m), 9.17 (2H, br.s), 9.47 (1H, s).
Elemental analysis Calculated as C ₂₁ H ₂₄ N ₃ O ₂ .HCl: C, 59.72; H, 5.97; N, 9.95.
Experimental value: C, 59.43; H, 5.69; N, 9.51.
MS m / z: 386 [M + H] ⁺

参考例１７７で得た6-(5-クロロペンタノイル)-3,4-ジヒドロ-2(1H)-キナゾリノンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点164-166℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.53-1.74 (4H, m), 2.30 (3H, s), 2.42-2.47 (2H, m), 2.57-2.63 (2H, m), 2.75-2.80 (2H, m), 2.89-2.93 (2H, m), 4.59 (2H, s), 5.50 (1H, s), 6.76 (1H, d, J = 8.1Hz), 7.30-7.18 (5H, m), 7.70 (1H, s), 7.78 (1H, dd, J = 8.1, 1.8Hz), 8.34 (1H, s).
元素分析 C₂₂H₂₇N₃O₂・HCl として
計算値：C, 62.92; H, 7.20; N, 10.01.
実験値：C, 62.59; H, 7.12; N, 10.13.
MS m/z: 386 [M+H]⁺ 6- {5- [Methyl (2-phenylethyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Using 6- (5-chloropentanoyl) -3,4-dihydro-2 (1H) -quinazolinone and N-methyl-N- (2-phenylethyl) amine obtained in Reference Example 177, Example 9 and By performing the same operation, the title compound was obtained as colorless crystals having a melting point of 164-166 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.53-1.74 (4H, m), 2.30 (3H, s), 2.42-2.47 (2H, m), 2.57-2.63 (2H, m), 2.75-2.80 (2H, m), 2.89-2.93 (2H, m), 4.59 (2H, s), 5.50 (1H, s), 6.76 (1H, d, J = 8.1Hz), 7.30-7.18 (5H, m), 7.70 (1H, s), 7.78 (1H, dd, J = 8.1, 1.8Hz), 8.34 (1H, s).
Elemental analysis Calculated as C ₂₂ H ₂₇ N ₃ O ₂ .HCl: C, 62.92; H, 7.20; N, 10.01.
Experimental value: C, 62.59; H, 7.12; N, 10.13.
MS m / z: 386 [M + H] ⁺

参考例１７７で得た6-(5-クロロペンタノイル)-3,4-ジヒドロ-2(1H)-キナゾリノンおよび2-(2-メトキシフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点170-171℃(分解)の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.79-1.63 (4H, m), 2.79 (3H, d, J = 4.8Hz), 3.02-2.95 (4H, m), 3.24-3.07 (4H, m), 3.80 (3H, s), 4.38 (2H, m), 6.94-6.84 (2H, m), 7.04-6.99 (2H, m), 7.30-7.20 (2H, m), 7.80-7.77 (2H, m), 9.47 (1H, s), 10.29 (1H, br.s).
元素分析 C₂₅H₂₉N₃O₃・HCl・1.5H₂O として
計算値：C, 60.19; H, 7.25; N, 9.16.
実験値：C, 60.69; H, 7.17; N, 9.38.
MS m/z: 396 [M+H]⁺ 6- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Using 6- (5-chloropentanoyl) -3,4-dihydro-2 (1H) -quinazolinone and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 177, the same procedure as in Example 9 was performed. This gave the title compound as colorless crystals having a melting point of 170-171 ° C. (decomposition).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.79-1.63 (4H, m), 2.79 (3H, d, J = 4.8Hz), 3.02-2.95 (4H, m), 3.24-3.07 (4H, m) , 3.80 (3H, s), 4.38 (2H, m), 6.94-6.84 (2H, m), 7.04-6.99 (2H, m), 7.30-7.20 (2H, m), 7.80-7.77 (2H, m) , 9.47 (1H, s), 10.29 (1H, br.s).
Elemental analysis _{C 25 H 29 N 3 O 3} · HCl · 1.5H 2 O Calculated: C, 60.19; H, 7.25 ; N, 9.16.
Experimental value: C, 60.69; H, 7.17; N, 9.38.
MS m / z: 396 [M + H] ⁺

参考例１７７で得た6-(5-クロロペンタノイル)-3,4-ジヒドロ-2(1H)-キナゾリノンおよび2-(2-クロロフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点192-195℃(分解)の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.79-1.64 (4H, m), 2.82 (3H, d, J = 4.8 Hz), 3.02-2.97 (2H, m), 3.26-3.10 (6H, m), 4.38 (2H, s), 6.85 (1H, d, J = 8.1 Hz), 7.04 (1H, s), 7.38-7.30 (2H, m), 7.49-7.44 (2H, m), 7.80-7.76 (2H, m), 9.47 (1H, s), 10.73 (1H, br.s).
元素分析 C₂₂H₂₅N₃O₂・HCl・0.5H₂O として
計算値：C, 59.33; H, 6.34; N, 9.43.
実験値：C, 59.22; H, 6.77; N, 9.58.
MS m/z: 400 [M+H]⁺ 6- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone hydrochloride

The same operation as in Example 9 is carried out using 6- (5-chloropentanoyl) -3,4-dihydro-2 (1H) -quinazolinone and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 177. This gave the title compound as colorless crystals having a melting point of 192-195 ° C. (decomposition).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.79-1.64 (4H, m), 2.82 (3H, d, J = 4.8 Hz), 3.02-2.97 (2H, m), 3.26-3.10 (6H, m) , 4.38 (2H, s), 6.85 (1H, d, J = 8.1 Hz), 7.04 (1H, s), 7.38-7.30 (2H, m), 7.49-7.44 (2H, m), 7.80-7.76 (2H m), 9.47 (1H, s), 10.73 (1H, br.s).
Elemental analysis Calculated as C ₂₂ H ₂₅ N ₃ O ₂ · HCl · 0.5H ₂ O: C, 59.33; H, 6.34; N, 9.43.
Experimental value: C, 59.22; H, 6.77; N, 9.58.
MS m / z: 400 [M + H] ⁺

参考例１７８で得た6-(5-クロロペンタノイル)-1,3-ジメチル-3,4-ジヒドロ-2(1H)-キナゾリノンおよびN-メチル-N-(2-フェニルエチル)アミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点174-176℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.79-1.62 (4H, m), 2.79 (3H, d, J = 4.8Hz), 2.92 (3H, s), 3.07-3.02 (4H, m), 3.24 (3H,s), 3.41-3.13 (4H, m), 4.45 (2H, s), 7.03 (1H, d, J = 8.7Hz), 7.38-7.24 (5H, m), 7.79 (1H, d, J = 1.8Hz), 7.92 (1H, dd, J = 8.7, 2.1 Hz), 10.58 (1H, br.s).
元素分析 C₂₄H₃₂N₃O₂・HCl・H₂O として
計算値：C, 67.04; H, 7.05; N, 9.77.
実験値：C, 66.42; H, 7.67; N, 9.87.
MS m/z: 394 [M+H]⁺ 1,3-Dimethyl-6- {5- [methyl (2-phenylethyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Using 6- (5-chloropentanoyl) -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone and N-methyl-N- (2-phenylethyl) amine obtained in Reference Example 178 In the same manner as in Example 9, the title compound was obtained as colorless crystals having a melting point of 174-176 ° C.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.79-1.62 (4H, m), 2.79 (3H, d, J = 4.8Hz), 2.92 (3H, s), 3.07-3.02 (4H, m), 3.24 (3H, s), 3.41-3.13 (4H, m), 4.45 (2H, s), 7.03 (1H, d, J = 8.7Hz), 7.38-7.24 (5H, m), 7.79 (1H, d, J = 1.8Hz), 7.92 (1H, dd, J = 8.7, 2.1 Hz), 10.58 (1H, br.s).
Elemental analysis Calculated as C ₂₄ H ₃₂ N ₃ O ₂ · HCl · H ₂ O: C, 67.04; H, 7.05; N, 9.77.
Experimental value: C, 66.42; H, 7.67; N, 9.87.
MS m / z: 394 [M + H] ⁺

参考例１７８で得た6-(5-クロロペンタノイル)-1,3-ジメチル-3,4-ジヒドロ-2(1H)-キナゾリノンおよび2-(2-メトキシフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点145-146℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.79-1.65 (4H, m), 2.78 (3H, s), 2.92 (3H, s), 3.18-2.96 (8H, m), 3.24 (3H, s), 3.81 (3H, s), 4.45 (2H, s), 6.94-6.89 (1H, m), 7.04-6.99 (2H, m), 7.30-7.21 (2H, m), 7.79 (1H, d, J = 1.8Hz), 7.92 (1H, dd, J = 8.6, 2.0Hz), 10.57 (1H, br.s).
元素分析 C₂₅H₃₄N₃O₃・HCl・H₂O として
計算値：C, 65.27; H, 7.45; N, 9.13.
実験値：C, 64.68; H, 7.58; N, 9.31.
MS m/z: 424 [M+H]⁺ 6- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Example 6 Using 6- (5-chloropentanoyl) -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone and 2- (2-methoxyphenyl) ethylamine obtained in Reference Example 178 The title compound was obtained as colorless crystals having a melting point of 145-146 ° C. by carrying out the same operation as in 9.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.79-1.65 (4H, m), 2.78 (3H, s), 2.92 (3H, s), 3.18-2.96 (8H, m), 3.24 (3H, s) , 3.81 (3H, s), 4.45 (2H, s), 6.94-6.89 (1H, m), 7.04-6.99 (2H, m), 7.30-7.21 (2H, m), 7.79 (1H, d, J = 1.8Hz), 7.92 (1H, dd, J = 8.6, 2.0Hz), 10.57 (1H, br.s).
Elemental analysis _{C 25 H 34 N 3 O 3} · HCl · H 2 O Calculated: C, 65.27; H, 7.45 ; N, 9.13.
Experimental value: C, 64.68; H, 7.58; N, 9.31.
MS m / z: 424 [M + H] ⁺

参考例１７８で得た6-(5-クロロペンタノイル)-1,3-ジメチル-3,4-ジヒドロ-2(1H)-キナゾリノンおよび2-(2-クロロフェニル)エチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を融点187-188℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.77-1.66 (4H, m), 2.82 (3H, s), 2.92 (3H, s), 3.07-3.02 (2H, m), 3.24 (3H, s), 3.40-3.00 (6H, m), 4.44 (2H,s), 7.03 (1H, d, J = 8.4 Hz), 7.37-7.30 (2H, m), 7.49-7.44 (2H, m), 7.79 (1H, s), 7.91 (1H, d, J = 8.4 Hz), 10.63 (1H, br.s).
元素分析 C₂₄H₃₀ClN₃O₂・HCl・2H₂O として
計算値：C, 61.99; H, 7.59; N, 9.04.
実験値：C, 61.97; H, 6.91; N, 9.31.
MS m/z: 428 [M+H]⁺ 6- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone hydrochloride

Using Example 6- (5-chloropentanoyl) -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone and 2- (2-chlorophenyl) ethylamine, Example 9 The title compound was obtained as colorless crystals having a melting point of 187 ° -188 ° C. by carrying out the same operation as in.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.77-1.66 (4H, m), 2.82 (3H, s), 2.92 (3H, s), 3.07-3.02 (2H, m), 3.24 (3H, s) , 3.40-3.00 (6H, m), 4.44 (2H, s), 7.03 (1H, d, J = 8.4 Hz), 7.37-7.30 (2H, m), 7.49-7.44 (2H, m), 7.79 (1H , s), 7.91 (1H, d, J = 8.4 Hz), 10.63 (1H, br.s).
Elemental analysis Calculated as C ₂₄ H ₃₀ ClN ₃ O ₂ · HCl · 2H ₂ O: C, 61.99; H, 7.59; N, 9.04.
Experimental values: C, 61.97; H, 6.91; N, 9.31.
MS m / z: 428 [M + H] ⁺

参考例１８０で得たベンジル[4-オキソ-4-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ブチル]カルバミン酸tert-ブチル(526mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(384mg) を融点159-161℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 2.01 (2H, t, J = 7.4Hz), 2.59 (2H, t, J = 7.6Hz), 2.80-3.25 (8H, m), 3.99 (2H, t, J = 8.4Hz), 4.05-4.20 (2H, m), 7.35-7.65 (5H, m), 7.72 (2H, s), 9.40-9.60 (2H, br). 8- [4- (Benzylamino) butanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

Benzyl [4-oxo-4- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) butyl] carbamine obtained in Reference Example 180 The same operation as in Example 1 was carried out using tert-butyl acid (526 mg) to give the title compound (384 mg) as colorless crystals having a melting point of 159-161 ° C.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 2.01 (2H, t, J = 7.4Hz), 2.59 (2H, t, J = 7.6Hz), 2.80-3.25 (8H, m), 3.99 (2H, t , J = 8.4Hz), 4.05-4.20 (2H, m), 7.35-7.65 (5H, m), 7.72 (2H, s), 9.40-9.60 (2H, br).

参考例１８１で得た2-(2-メトキシフェニル)エチル[4-オキソ-4-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ブチル]カルバミン酸tert-ブチル(790mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(452mg) を融点165-167℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.85-2.10 (2H, m), 2.60 (2H, t, J = 7.6Hz), 2.90-3.25 (12H, m), 3.81 (3H, s), 4.00 (2H, t, J = 8.4Hz), 6.92 (1H, dt, J = 7.3, 1.2Hz), 7.00 (1H, d, J = 7.3Hz), 7.15-7.30 (2H, m), 7.74 (2H, s), 9.00-9.20 (2H, br).
元素分析 C₂₄H₂₉ClN₂O₃・0.5H₂O として
計算値：C, 65.82; H, 6.90; N, 6.40.
実験値：C, 65.37; H, 6.68; N, 6.34. 8- (4-{[2- (2-methoxyphenyl) ethyl] amino} butanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

2- (2-methoxyphenyl) ethyl [4-oxo-4- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Reference Example 181 The title compound (452 mg) was obtained as colorless crystals with a melting point of 165-167 ° C. by the same procedure as in Example 1 using tert-butyl (-8-yl) butyl] carbamate (790 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.85-2.10 (2H, m), 2.60 (2H, t, J = 7.6Hz), 2.90-3.25 (12H, m), 3.81 (3H, s), 4.00 (2H, t, J = 8.4Hz), 6.92 (1H, dt, J = 7.3, 1.2Hz), 7.00 (1H, d, J = 7.3Hz), 7.15-7.30 (2H, m), 7.74 (2H, s), 9.00-9.20 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₂₉ ClN ₂ O ₃ · 0.5H ₂ O: C, 65.82; H, 6.90; N, 6.40.
Experimental value: C, 65.37; H, 6.68; N, 6.34.

参考例１８２で得たベンジル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸tert-ブチル(498mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(340mg) を融点123-125℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.55-1.85 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.05 (6H, m), 3.17 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 4.05-4.20 (2H, m), 7.35-7.65 (5H, m), 7.73 (2H, s), 9.40-9.60 (2H, br). 8- [5- (Benzylamino) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

Benzyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) pentyl] carbamine obtained in Reference Example 182 The title compound (340 mg) was obtained as colorless crystals having a melting point of 123-125 ° C. by carrying out the same operation as in Example 1 using tert-butyl acid (498 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.55-1.85 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.05 (6H, m), 3.17 (2H, t, J = 8.4Hz), 3.99 (2H, t, J = 8.4Hz), 4.05-4.20 (2H, m), 7.35-7.65 (5H, m), 7.73 (2H, s), 9.40-9.60 (2H, br).

参考例１８３で得た2-メトキシベンジル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸tert-ブチル(524mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(381mg) を融点90-92℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.55-1.80 (4H, m), 2.60 (2H, t, J = 7.6Hz), 2.80-3.05 (6H, m), 3.18 (2H, t, J = 8.4Hz), 3.75-4.10 (4H, m), 3.84 (3H, s), 6.95-7.15 (2H, m), 7.35-7.50 (2H, m), 7.73 (2H, s), 8.90-9.10 (2H, br). 8- {5-[(2-methoxybenzyl) amino] pentanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

2-Methoxybenzyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) obtained in Reference Example 183 The title compound (381 mg) was obtained as colorless crystals with a melting point of 90-92 ° C. by the same procedure as in Example 1 using tert-butyl pentyl] carbamate (524 mg).
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.55-1.80 (4H, m), 2.60 (2H, t, J = 7.6Hz), 2.80-3.05 (6H, m), 3.18 (2H, t, J = 8.4Hz), 3.75-4.10 (4H, m), 3.84 (3H, s), 6.95-7.15 (2H, m), 7.35-7.50 (2H, m), 7.73 (2H, s), 8.90-9.10 (2H , br).

参考例１８４で得たベンジル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸tert-ブチル(554mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(360mg) を融点181-183℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.80-3.00 (6H, m), 3.17 (2H, t, J = 8.4Hz), 3.98 (2H, t, J = 8.4Hz), 4.05-4.20 (2H, m), 7.35-7.65 (5H, m), 7.72 (2H, s), 9.35-9.55 (2H, br).
元素分析 C₂₄H₂₉ClN₂O₂・1.5H₂O として
計算値：C, 65.52; H, 7.33; N, 6.37.
実験値：C, 65.53; H, 7.25; N, 6.17. 8- [6- (Benzylamino) hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

Benzyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) hexyl] carbamine obtained in Reference Example 184 The title compound (360 mg) was obtained as colorless crystals having a melting point of 181-183 ° C. by performing the same operation as in Example 1 using tert-butyl acid (554 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.80-3.00 (6H, m) , 3.17 (2H, t, J = 8.4Hz), 3.98 (2H, t, J = 8.4Hz), 4.05-4.20 (2H, m), 7.35-7.65 (5H, m), 7.72 (2H, s), 9.35-9.55 (2H, br).
Elemental analysis Calculated as C ₂₄ H ₂₉ ClN ₂ O ₂ .1.5H ₂ O: C, 65.52; H, 7.33; N, 6.37.
Experimental values: C, 65.53; H, 7.25; N, 6.17.

参考例１８５で得た2-メトキシベンジル[6-オキソ-6-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ヘキシル]カルバミン酸tert-ブチル(486mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(393mg) を淡黄色非晶状粉末として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.90-3.00 (4H, m), 3.16 (2H, t, J = 8.4Hz), 3.84 (3H, s), 3.90-4.15 (6H, m), 6.99 (1H, t, J = 7.5Hz), 7.09 (1H, d, J = 8.0 Hz), 7.41 (1H, t, J = 8.0Hz), 7.51 (1H, d, J = 7.5Hz), 7.73 (2H, s), 9.00-9.20 (2H, br). 8- {6-[(2-methoxybenzyl) amino] hexanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

2-Methoxybenzyl [6-oxo-6- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-8-yl) obtained in Reference Example 185 The same operation as in Example 1 was carried out using hexyl] carbamate tert-butyl (486 mg) to give the titled compound (393 mg) as a pale yellow amorphous powder.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.80 (4H, m), 2.59 (2H, t, J = 7.5Hz), 2.90-3.00 (4H, m) , 3.16 (2H, t, J = 8.4Hz), 3.84 (3H, s), 3.90-4.15 (6H, m), 6.99 (1H, t, J = 7.5Hz), 7.09 (1H, d, J = 8.0 Hz), 7.41 (1H, t, J = 8.0Hz), 7.51 (1H, d, J = 7.5Hz), 7.73 (2H, s), 9.00-9.20 (2H, br).

参考例１８６で得た6-オキソ-6-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ヘキシル(2-フェニルエチル)カルバミン酸tert-ブチル(842mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(490mg) を融点208-210℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.55-1.70 (4H, m), 2.85-3.00 (6H, m), 3.05-3.20 (2H, m), 4.68 (2H, s), 7.05 (1H, d, J = 8.4Hz), 7.10-7.20 (5H, m), 7.51 (1H, s), 7.62 (1H, dd, J = 8.4, 2.1Hz), 8.80-9.05 (2H, br), 10.91 (1H, s). 6- {6-[(2-Phenylethyl) amino] hexanoyl} -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

Tert-Butyl 6-oxo-6- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) hexyl (2-phenylethyl) carbamate (842 mg) obtained in Reference Example 186 ) To give the title compound (490 mg) as colorless crystals with a melting point of 208-210 ° C. by a similar operation as in Example 1.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.70 (4H, m), 2.85-3.00 (6H, m), 3.05-3.20 (2H, m), 4.68 ( 2H, s), 7.05 (1H, d, J = 8.4Hz), 7.10-7.20 (5H, m), 7.51 (1H, s), 7.62 (1H, dd, J = 8.4, 2.1Hz), 8.80-9.05 (2H, br), 10.91 (1H, s).

参考例１８７で得た2-(2-メトキシフェニル)エチル[6-オキソ-6-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ヘキシル]カルバミン酸tert-ブチル(974mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(567mg) を融点151-153℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.10 (8H, m), 3.80 (3H, s), 4.68 (2H, s), 6.91 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 7.8Hz), 7.05 (1H, d, J = 8.6Hz), 7.19 (1H, d, J = 7.5Hz), 7.26 (1H, dt, J = 7.8, 1.8Hz), 7.53 (1H, t, J = 1.8Hz), 7.62 (1H, dd, J = 8.6, 1.8Hz), 8.90-9.10 (2H, br), 10.94 (1H, s). 6- (6-{[2- (2-methoxyphenyl) ethyl] amino} hexanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (2-Methoxyphenyl) ethyl [6-oxo-6- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) hexyl] carbamic acid obtained in Reference Example 187 The title compound (567 mg) was obtained as colorless crystals having a melting point of 151-153 ° C. by carrying out the same operation as in Example 1 using tert-butyl (974 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.80-3.10 (8H, m), 3.80 (3H, s), 4.68 (2H, s), 6.91 (1H, t, J = 7.5Hz), 7.00 (1H, d, J = 7.8Hz), 7.05 (1H, d, J = 8.6Hz), 7.19 (1H, d, J = 7.5Hz) , 7.26 (1H, dt, J = 7.8, 1.8Hz), 7.53 (1H, t, J = 1.8Hz), 7.62 (1H, dd, J = 8.6, 1.8Hz), 8.90-9.10 (2H, br), 10.94 (1H, s).

参考例１８８で得た2-(2-クロロフェニル)エチル[6-オキソ-6-(3-オキソ-3,4-ジヒドロ-2H-1,4-ベンゾオキサジン-6-イル)ヘキシル]カルバミン酸tert-ブチル(974mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(387mg) を融点183-185℃の無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.85-3.20 (8H, m), 4.68 (2H, s), 7.05 (1H, d, J = 8.7Hz), 7.25-7.55 (5H, m), 7.62 (1H, dd, J = 8.4, 1.8Hz), 8.80-9.20 (2H, br), 10.92 (1H, s). 6- (6-{[2- (2-Chlorophenyl) ethyl] amino} hexanoyl) -2H-1,4-benzoxazin-3 (4H) -one hydrochloride

2- (2-Chlorophenyl) ethyl [6-oxo-6- (3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl) hexyl] carbamic acid tert obtained in Reference Example 188 The title compound (387 mg) was obtained as colorless crystals having a melting point of 183-185 ° C. by conducting the same operation as in Example 1 using -butyl (974 mg).
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.30-1.45 (2H, m), 1.55-1.75 (4H, m), 2.85-3.20 (8H, m), 4.68 (2H, s), 7.05 (1H, d, J = 8.7Hz), 7.25-7.55 (5H, m), 7.62 (1H, dd, J = 8.4, 1.8Hz), 8.80-9.20 (2H, br), 10.92 (1H, s).

参考例１７９で得た8-(4-クロロブタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2-フェニルエチルアミン(870mg) を用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物(500mg) を無色結晶として得た。
¹H NMR (300MHz, DMSO-d₆) δ 1.90-2.05 (2H, m), 2.60 (2H, t, J = 7.6Hz), 2.90-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.20-7.40 (5H, m), 7.74 (2H, s), 9.00-9.20 (2H, br). 8- {4-[(2-Phenylethyl) amino] butanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

8- (4-Chlorobutanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 179 and 2- The same operation as in Reference Example 19 and Example 1 was sequentially performed using phenylethylamine (870 mg) to obtain the title compound (500 mg) as colorless crystals.
¹ H NMR (300MHz, DMSO-d ₆ ) δ 1.90-2.05 (2H, m), 2.60 (2H, t, J = 7.6Hz), 2.90-3.25 (12H, m), 3.99 (2H, t, J = 8.4Hz), 7.20-7.40 (5H, m), 7.74 (2H, s), 9.00-9.20 (2H, br).

参考例１で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および1,2,3,4-テトラヒドロイソキノリン(457mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(779mg) を融点203-205℃の無色結晶として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.60-1.90 (4H, m), 2.55 (2H, t, J = 7.2Hz), 2.60-2.80 (4H, m), 2.88 (2H, t, J = 5.7Hz), 2.90-3.00 (4H, m), 3.17 (2H, t, J = 8.4Hz), 3.61 (2H, s), 4.10 (2H, t, J = 8.4Hz), 6.95-7.15 (4H, m), 7.67 (1H, s), 7.71 (1H, s). 8- [5- (3,4-Dihydro-2 (1H) -isoquinolinyl) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one hydrochloric acid salt

8- (5-Chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 1, The same operation as in Example 9 was carried out using 2,3,4-tetrahydroisoquinoline (457 mg) to give the title compound (779 mg) as colorless crystals having a melting point of 203-205 ° C.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.60-1.90 (4H, m), 2.55 (2H, t, J = 7.2 Hz), 2.60-2.80 (4H, m), 2.88 (2H, t, J = 5.7Hz), 2.90-3.00 (4H, m), 3.17 (2H, t, J = 8.4Hz), 3.61 (2H, s), 4.10 (2H, t, J = 8.4Hz), 6.95-7.15 (4H m), 7.67 (1H, s), 7.71 (1H, s).

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.50g) およびメタンスルホン酸2-(2-メトキシフェニル)エチル(1.16g) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(1.69g) を融点209-211℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.50 (3H, m), 1.60-2.10 (6H, m), 2.40-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz), 3.81 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.80-6.95 (2H, m), 7.10-7.25 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₈H₃₄N₂O₃・HCl・0.5H₂Oとして
計算値：C, 68.35; H, 7.37; N, 5.69.
実験値：C, 68.85; H, 7.54; N, 5.84. 8- (3- {1- [2- (2-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.50 g) and methanesulfonic acid 2- Using the same procedure as in Example 81 using (2-methoxyphenyl) ethyl (1.16 g), the title compound (1.69 g) was obtained as colorless crystals having a melting point of 209-211 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.50 (3H, m), 1.60-2.10 (6H, m), 2.40-3.10 (12H, m), 3.23 (2H, t, J = 8.4 Hz ), 3.81 (3H, s), 4.13 (2H, t, J = 8.4Hz), 6.80-6.95 (2H, m), 7.10-7.25 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis _{C 28 H 34 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 68.35; H, 7.37 ; N, 5.69.
Experimental value: C, 68.85; H, 7.54; N, 5.84.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.50g) およびメタンスルホン酸2-(3-メトキシフェニル)エチル(1.16g) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(1.53g) を融点240-242℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.55-2.10 (6H, m), 2.50-3.10 (12H, m), 3.23 (2H, t, J = 8.4Hz), 3.79 (3H, s), 4.14 (2H, t, J = 8.4Hz), 6.70-6.85 (3H, m), 7.15-7.30 (1H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₈H₃₄N₂O₃・HCl・0.5H₂Oとして
計算値：C, 68.35; H, 7.37; N, 5.69.
実験値：C, 68.92; H, 6.69; N, 5.87. 8- (3- {1- [2- (3-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.50 g) and methanesulfonic acid 2- The title compound (1.53 g) was obtained as colorless crystals having a melting point of 240-242 ° C. by carrying out the same operation as in Example 81 using (3-methoxyphenyl) ethyl (1.16 g).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.55-2.10 (6H, m), 2.50-3.10 (12H, m), 3.23 (2H, t, J = 8.4 Hz ), 3.79 (3H, s), 4.14 (2H, t, J = 8.4Hz), 6.70-6.85 (3H, m), 7.15-7.30 (1H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis _{C 28 H 34 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 68.35; H, 7.37 ; N, 5.69.
Experimental value: C, 68.92; H, 6.69; N, 5.87.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オンおよびメタンスルホン酸2-(4-メトキシフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を融点141-143℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.30-1.60 (3H, m), 1.65-1.85 (4H, m), 2.00-2.20 (2H, m), 2.60-3.15 (12H, m), 3.23 (2H, t, J = 8.4Hz), 3.78 (3H, s), 4.14 (2H, t, J = 8.4Hz), 6.83 (2H, d, J = 8.6Hz), 7.13 (2H, d, J = 8.6Hz), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₈H₃₄ClN₂O₃・HCl・H₂Oとして
計算値：C, 67.12; H, 7.44; N, 5.59.
実験値：C, 67.29; H, 7.56; N, 5.32. 8- (3- {1- [2- (4-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one and 2- (4-methoxy) methane sulfonate The title compound was obtained as colorless crystals with a melting point of 141-143 ° C. by conducting the same operation as in Example 81 using phenyl) ethyl.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.30-1.60 (3H, m), 1.65-1.85 (4H, m), 2.00-2.20 (2H, m), 2.60-3.15 (12H, m), 3.23 (2H, t, J = 8.4Hz), 3.78 (3H, s), 4.14 (2H, t, J = 8.4Hz), 6.83 (2H, d, J = 8.6Hz), 7.13 (2H, d, J = 8.6Hz), 7.67 (1H, s), 7.72 (1H, s).
Elemental analysis _{C 28 H 34 ClN 2 O 3} · HCl · H 2 O Calculated: C, 67.12; H, 7.44 ; N, 5.59.
Experimental values: C, 67.29; H, 7.56; N, 5.32.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オンおよびメタンスルホン酸2-(2-エトキシフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を融点182-184℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.30-1.50 (3H, m), 1.41 (3H, t, J = 7.0Hz), 1.65-1.85 (4H, m), 1.95-2.10 (2H, m), 2.50-2.65 (2H, m), 2.71 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.03 (2H, q, J = 7.0Hz), 4.14 (2H, t, J = 8.4Hz), 6.75-6.90 (2H, m), 7.10-7.20 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₉H₃₆N₂O₃・HCl・H₂Oとして
計算値：C, 67.62; H, 7.63; N, 5.44.
実験値：C, 67.08; H, 7.24; N, 5.28. 8- (3- {1- [2- (2-Ethoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one and 2- (2-ethoxy) methane sulfonate The title compound was obtained as colorless crystals having a melting point of 182-184 ° C. by performing the same operation as in Example 81 using phenyl) ethyl.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.30-1.50 (3H, m), 1.41 (3H, t, J = 7.0 Hz), 1.65-1.85 (4H, m), 1.95-2.10 (2H, m ), 2.50-2.65 (2H, m), 2.71 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.03 (2H, q, J = 7.0Hz), 4.14 (2H, t, J = 8.4Hz), 6.75-6.90 (2H, m), 7.10-7.20 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₉ H ₃₆ N ₂ O ₃ · HCl · H ₂ O: C, 67.62; H, 7.63; N, 5.44.
Experimental value: C, 67.08; H, 7.24; N, 5.28.

実施例３０９で得た8-(3-{1-[2-(2-メトキシフェニル)エチル]-4-ピペリジニル}プロパノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(800mg) の臭化水素酸(15ml) 溶液を140℃で1時間攪拌した。反応液を炭酸カリウム水溶液でpH＝12とした後、酢酸エチルで抽出した。抽出液を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去することにより、表題化合物のフリー塩基体(622mg) を融点143-145℃の無色結晶として得た。
上記フリー塩基体(500mg) を塩化水素−エタノール溶液で処理することにより、表題化合物(432mg) を融点220-222℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.25-1.50 (3H, m), 1.65-1.90 (4H, m), 2.05-2.20 (2H, m), 2.60-2.70 (2H, m), 2.72 (2H, t, J = 7.8Hz), 2.75-2.85 (3H, m), 2.94 (2H, t, J = 7.8Hz), 3.03 (2H, t, J = 7.8Hz), 3.10-3.20 (2H, m), 3.26 (2H, t, J = 8.5Hz), 4.14 (2H, t, J = 8.5Hz), 6.73 (1H, dt, J = 7.3, 1.2Hz), 6.87 (1H, dd, J = 5.2, 0.8Hz), 6.98 (1H, dd, J = 4.8, 0.8Hz), 7.12 (1H, dt, J = 7.9, 1.5Hz), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₂N₂O₃・HCl・0.5H₂Oとして
計算値：C, 67.84; H, 7.17; N, 5.86.
実験値：C, 67.78; H, 7.51; N, 5.87. 8- (3- {1- [2- (2-hydroxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- (3- {1- [2- (2-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2 obtained in Example 309 , 1-ij] quinolin-4-one (800 mg) in hydrobromic acid (15 ml) was stirred at 140 ° C. for 1 hour. The reaction solution was adjusted to pH = 12 with an aqueous potassium carbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give the free base of the title compound (622 mg) as colorless crystals having a melting point of 143-145 ° C.
The above free base (500 mg) was treated with a hydrogen chloride-ethanol solution to give the title compound (432 mg) as colorless crystals having a melting point of 220-222 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.25-1.50 (3H, m), 1.65-1.90 (4H, m), 2.05-2.20 (2H, m), 2.60-2.70 (2H, m), 2.72 (2H, t, J = 7.8Hz), 2.75-2.85 (3H, m), 2.94 (2H, t, J = 7.8Hz), 3.03 (2H, t, J = 7.8Hz), 3.10-3.20 (2H, m), 3.26 (2H, t, J = 8.5Hz), 4.14 (2H, t, J = 8.5Hz), 6.73 (1H, dt, J = 7.3, 1.2Hz), 6.87 (1H, dd, J = 5.2 , 0.8Hz), 6.98 (1H, dd, J = 4.8, 0.8Hz), 7.12 (1H, dt, J = 7.9, 1.5Hz), 7.67 (1H, s), 7.72 (1H, s).
Elemental analysis _{C 27 H 32 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 67.84; H, 7.17 ; N, 5.86.
Experimental value: C, 67.78; H, 7.51; N, 5.87.

実施例３１０で得た8-(3-{1-[2-(3-メトキシフェニル)エチル]-4-ピペリジニル}プロパノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オンを用いて、実施例３１３と同様の操作を行うことにより、表題化合物を融点229-231℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.55 (3H, m), 1.60-1.85 (4H, m),1.90-2.20 (2H, m), 2.55-3.15 (13H, m), 3.27 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 6.60-6.75 (3H, m), 7.10-7.20 (1H, m), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₂N₂O₃・HCl・0.5H₂Oとして
計算値：C, 67.84; H, 7.17; N, 5.86.
実験値：C, 68.07; H, 7.35; N, 5.69. 8- (3- {1- [2- (3-hydroxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- (3- {1- [2- (3-methoxyphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2 obtained in Example 310 , 1-ij] quinolin-4-one, and the title compound was obtained as colorless crystals having a melting point of 229-231 ° C. by a similar operation as in Example 313.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.55 (3H, m), 1.60-1.85 (4H, m), 1.90-2.20 (2H, m), 2.55-3.15 (13H, m), 3.27 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 6.60-6.75 (3H, m), 7.10-7.20 (1H, m), 7.67 (1H, s), 7.72 ( 1H, s).
Elemental analysis _{C 27 H 32 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 67.84; H, 7.17 ; N, 5.86.
Experimental value: C, 68.07; H, 7.35; N, 5.69.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびメタンスルホン酸2-(3-メチルフェニル)エチル(360mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(391mg) を融点197-199℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.25-1.50 (3H, m), 1.60-1.85 (4H, m), 1.90-2.10 (2H, m), 2.32 (3H, s), 2.45-3.10 (12H, m), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 6.95-7.20 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₈H₃₄N₂O₂・HCl・0.5H₂Oとして
計算値：C, 70.64; H, 7.62; N, 5.88.
実験値：C, 70.53; H, 7.52; N, 5.91. 8- (3- {1- [2- (3-methylphenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and methanesulfonic acid 2- ( The same operation as in Example 81 was carried out using 3-methylphenyl) ethyl (360 mg) to give the title compound (391 mg) as colorless crystals having a melting point of 197-199 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.25-1.50 (3H, m), 1.60-1.85 (4H, m), 1.90-2.10 (2H, m), 2.32 (3H, s), 2.45-3.10 (12H, m), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 6.95-7.20 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₈ H ₃₄ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 70.64; H, 7.62; N, 5.88.
Experimental value: C, 70.53; H, 7.52; N, 5.91.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) およびメタンスルホン酸2-(2-クロロフェニル)エチル(475mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(303mg) を融点207-210℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.60-1.80 (4H, m), 1.95-2.10 (2H, m), 2.50-2.60 (2H, m), 2.72 (2H, t, J = 7.6Hz), 2.85-3.10 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.10-7.40 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₁ClN₂O₂・HCl・0.5H₂Oとして
計算値：C, 65.32; H, 6.70; N, 5.64.
実験値：C, 65.77; H, 6.87; N, 5.63. 8- (3- {1- [2- (2-chlorophenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- 4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and methanesulfonic acid 2- ( The title compound (303 mg) was obtained as colorless crystals having a melting point of 207-210 ° C. by the same procedure as in Example 81 using 2-chlorophenyl) ethyl (475 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.60-1.80 (4H, m), 1.95-2.10 (2H, m), 2.50-2.60 (2H, m), 2.72 (2H, t, J = 7.6Hz), 2.85-3.10 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.10-7.40 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₁ ClN ₂ O ₂ · HCl · 0.5H ₂ O: C, 65.32; H, 6.70; N, 5.64.
Experimental values: C, 65.77; H, 6.87; N, 5.63.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オンおよびメタンスルホン酸2-(4-クロロフェニル)エチルを用いて、実施例８１と同様の操作を行うことにより、表題化合物を融点204-206℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.40-1.90 (7H, m), 2.10-2.30 (2H, m), 2.72 (2H, t, J = 7.8Hz), 2.85-3.30 (12H, m), 4.14 (2H, t, J = 8.4Hz), 7.10-7.30 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₇H₃₁ClN₂O₂・HCl・H₂Oとして
計算値：C, 64.16; H, 6.78; N, 5.54.
実験値：C, 64.15; H, 7.04; N, 5.25. 8- (3- {1- [2- (4-chlorophenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- 4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one and 2- (4-chlorophenyl) methanesulfonate ) Using ethyl, the title compound was obtained as colorless crystals having the melting point of 204-206 ° C by the same operation as in Example 81.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.40-1.90 (7H, m), 2.10-2.30 (2H, m), 2.72 (2H, t, J = 7.8Hz), 2.85-3.30 (12H, m ), 4.14 (2H, t, J = 8.4Hz), 7.10-7.30 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₁ ClN ₂ O ₂ · HCl · H ₂ O: C, 64.16; H, 6.78; N, 5.54.
Experimental value: C, 64.15; H, 7.04; N, 5.25.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および1-(2-ブロモエチル)-4-ニトロベンゼン(368mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(443mg) を融点217-219℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.25-1.55 (3H, m), 1.60-1.85 (4H, m), 1.95-2.20 (2H, m), 2.60-2.75 (4H, m), 2.85-3.15 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.37 (2H, d, J = 8.6Hz), 7.67 (1H, s), 7.72 (1H, s), 8.14 (2H, d, J = 8.6Hz).
元素分析 C₂₇H₃₁N₃O₄・HCl・0.5H₂Oとして
計算値：C, 63.96; H, 6.56; N, 8.29.
実験値：C, 63.67; H, 6.77; N, 8.25. 8- (3- {1- [2- (4-Nitrophenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 1- (2-bromoethyl ) -4-Nitrobenzene (368 mg) was used in the same manner as in Example 81 to obtain the title compound (443 mg) as colorless crystals having a melting point of 217-219 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.25-1.55 (3H, m), 1.60-1.85 (4H, m), 1.95-2.20 (2H, m), 2.60-2.75 (4H, m), 2.85 -3.15 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.37 (2H, d, J = 8.6Hz), 7.67 (1H, s) , 7.72 (1H, s), 8.14 (2H, d, J = 8.6Hz).
Elemental analysis Calculated as C ₂₇ H ₃₁ N ₃ O ₄ · HCl · 0.5H ₂ O: C, 63.96; H, 6.56; N, 8.29.
Experimental value: C, 63.67; H, 6.77; N, 8.25.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) およびメタンスルホン酸2-(2,6-ジクロロフェニル)エチル(545mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(272mg) を融点226-229℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.25-1.50 (3H, m), 1.60-1.80 (4H, m), 2.00-2.20 (2H, m), 2.50-2.60 (2H, m), 2.68 (2H, t, J = 7.6Hz), 2.85-3.30 (10H, m), 4.14 (2H, t, J = 8.4Hz), 7.00-7.10 (1H, m), 7.20-7.30 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₀Cl₂N₂O₂・HCl・0.5H₂Oとして
計算値：C, 61.08; H, 6.08; N, 5.28.
実験値：C, 60.96; H, 6.32; N, 5.04. 8- (3- {1- [2- (2,6-dichlorophenyl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] Quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and methanesulfonic acid 2- ( The title compound (272 mg) was obtained as colorless crystals having a melting point of 226-229 ° C. by carrying out the same operation as in Example 81 using 2,6-dichlorophenyl) ethyl (545 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.25-1.50 (3H, m), 1.60-1.80 (4H, m), 2.00-2.20 (2H, m), 2.50-2.60 (2H, m), 2.68 (2H, t, J = 7.6Hz), 2.85-3.30 (10H, m), 4.14 (2H, t, J = 8.4Hz), 7.00-7.10 (1H, m), 7.20-7.30 (2H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₀ Cl ₂ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 61.08; H, 6.08; N, 5.28.
Experimental value: C, 60.96; H, 6.32; N, 5.04.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および3-(2-ブロモエチル)-1H-インドール(394mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(370mg) を融点157-159℃の無色結晶として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.25-1.50 (3H, m), 1.60-1.85 (4H, m), 1.95-2.10 (2H, m), 2.60-2.80 (4H, m), 2.85-3.15 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.00-7.25 (3H, m), 7.36 (1H, d, J = 8.1Hz), 7.62 (1H, d, J = 8.1Hz), 7.68 (1H, s), 7.73 (1H, s), 8.00-8.25 (1H, br).
元素分析 C₂₈H₃₃N₃O₂・HCl・H₂Oとして
計算値：C, 68.29; H, 7.11; N, 8.24.
実験値：C, 68.77; H, 7.44; N, 7.94. 8- (3- {1- [2- (1H-Indol-3-yl) ethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 3- (2-bromoethyl ) -1H-indole (394 mg) was used in the same manner as in Example 81 to give the title compound (370 mg) as colorless crystals with a melting point of 157-159 ° C.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.25-1.50 (3H, m), 1.60-1.85 (4H, m), 1.95-2.10 (2H, m), 2.60-2.80 (4H, m), 2.85 -3.15 (8H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.00-7.25 (3H, m), 7.36 (1H, d, J = 8.1 Hz), 7.62 (1H, d, J = 8.1Hz), 7.68 (1H, s), 7.73 (1H, s), 8.00-8.25 (1H, br).
Elemental analysis Calculated as C ₂₈ H ₃₃ N ₃ O ₂ · HCl · H ₂ O: C, 68.29; H, 7.11; N, 8.24.
Experimental value: C, 68.77; H, 7.44; N, 7.94.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) および(±)-メタンスルホン酸1-メチル-2-フェニルエチル(528mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(257mg) を融点211-213℃の無色結晶として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 0.94 (3H, d, J = 6.6Hz), 1.20-1.45 (3H, m), 1.60-1.85 (4H, m), 2.10-2.45 (3H, m), 2.60-3.10 (10H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.10-7.40 (5H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₈H₃₄N₂O₂・HCl・0.5H₂Oとして
計算値：C, 70.64; H, 7.62; N, 5.88.
実験値：C, 70.80; H, 7.59; N, 5.88. (±) -8- {3- [1- (1-Methyl-2-phenylethyl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) and (±) -methanesulfone The title compound (257 mg) was obtained as colorless crystals having a melting point of 211-213 ° C. by conducting the same operation as in Example 81 using 1-methyl-2-phenylethyl acid (528 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 0.94 (3H, d, J = 6.6 Hz), 1.20-1.45 (3H, m), 1.60-1.85 (4H, m), 2.10-2.45 (3H, m ), 2.60-3.10 (10H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.10-7.40 (5H, m), 7.68 (1H, s) , 7.72 (1H, s).
Elemental analysis Calculated as C ₂₈ H ₃₄ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 70.64; H, 7.62; N, 5.88.
Experimental value: C, 70.80; H, 7.59; N, 5.88.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および(±)-メタンスルホン酸2-(2-メトキシフェニル)-1-メチルエチル(516mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(204mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 0.93 (3H, d, J = 6.6Hz), 1.20-1.40 (3H, m), 1.60-1.80 (4H, m), 2.20-2.45 (3H, m), 2.71 (2H, t, J = 7.8Hz), 2.80-3.05 (8H, m), 3.22 (2H, t, J = 8.4Hz), 3.80 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.90 (2H, m), 7.05-7.20 (2H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₉H₃₆N₂O₃・HCl・H₂Oとして
計算値：C, 67.62; H, 7.63; N, 5.44.
実験値：C, 67.65; H, 7.52; N, 5.42. (±) -8- (3- {1- [2- (2-methoxyphenyl) -1-methylethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3 , 2,1-ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and (±) -methanesulfone Using the acid 2- (2-methoxyphenyl) -1-methylethyl (516 mg), the title compound (204 mg) was obtained as a pale yellow amorphous powder by the same operation as in Example 81.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 0.93 (3H, d, J = 6.6 Hz), 1.20-1.40 (3H, m), 1.60-1.80 (4H, m), 2.20-2.45 (3H, m ), 2.71 (2H, t, J = 7.8Hz), 2.80-3.05 (8H, m), 3.22 (2H, t, J = 8.4Hz), 3.80 (3H, s), 4.12 (2H, t, J = 8.4Hz), 6.80-6.90 (2H, m), 7.05-7.20 (2H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis Calculated as C ₂₉ H ₃₆ N ₂ O ₃ · HCl · H ₂ O: C, 67.62; H, 7.63; N, 5.44.
Experimental value: C, 67.65; H, 7.52; N, 5.42.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg) および(±)-メタンスルホン酸1-メチル-2-フェノキシエチル(566mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(559mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.19 (3H, d, J = 6.6Hz), 1.20-1.45 (3H, m), 1.60-1.80 (4H, m), 2.00-2.50 (3H, m), 2.71 (2H, t, J = 7.8Hz), 2.80-3.10 (6H, m), 3.22 (2H, t, J = 8.4Hz), 3.87 (1H, dd, J = 9.4, 6.2Hz), 4.00-4.20 (3H, m), 6.80-7.00 (3H, m), 7.20-7.35 (2H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₈H₃₄N₂O₃・HCl・0.5H₂Oとして
計算値：C, 68.35; H, 7.37; N, 5.69.
実験値：C, 68.37; H, 7.57; N, 5.63. (±) -8- {3- [1- (1-Methyl-2-phenoxyethyl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg) and (±) -methanesulfone The title compound (559 mg) was obtained as a pale-yellow amorphous powder by the same procedure as in Example 81 using 1-methyl-2-phenoxyethyl acid (566 mg).
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.19 (3H, d, J = 6.6 Hz), 1.20-1.45 (3H, m), 1.60-1.80 (4H, m), 2.00-2.50 (3H, m ), 2.71 (2H, t, J = 7.8Hz), 2.80-3.10 (6H, m), 3.22 (2H, t, J = 8.4Hz), 3.87 (1H, dd, J = 9.4, 6.2Hz), 4.00 -4.20 (3H, m), 6.80-7.00 (3H, m), 7.20-7.35 (2H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis _{C 28 H 34 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 68.35; H, 7.37 ; N, 5.69.
Experimental value: C, 68.37; H, 7.57; N, 5.63.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および(±)-メタンスルホン酸2-(2-メトキシフェノキシ)-1-メチルエチル(550mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(181mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.19 (3H, d, J = 6.6Hz), 1.20-1.40 (3H, m), 1.60-1.80 (4H, m), 2.25-2.40 (2H, m), 2.72 (2H, t, J = 7.8Hz), 2.85-3.15 (7H, m), 3.22 (2H, t, J = 8.4Hz), 3.80-3.90 (1H, m), 3.85 (3H, s), 4.10-4.20 (3H, m), 6.85-7.00 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₉H₃₆N₂O₄・HCl・0.5H₂Oとして
計算値：C, 66.72; H, 7.34; N, 5.37.
実験値：C, 66.33; H, 7.54; N, 5.28. (±) -Methanesulfonic acid 8- (3- {1- [2- (2-methoxyphenoxy) -1-methylethyl] -4-piperidinyl} propanoyl) -1,2,5,6-tetrahydro-4H- Pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and (±) -methanesulfone Using the acid 2- (2-methoxyphenoxy) -1-methylethyl (550 mg), the title compound (181 mg) was obtained as a pale yellow amorphous powder by the same operation as in Example 81.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.19 (3H, d, J = 6.6 Hz), 1.20-1.40 (3H, m), 1.60-1.80 (4H, m), 2.25-2.40 (2H, m ), 2.72 (2H, t, J = 7.8Hz), 2.85-3.15 (7H, m), 3.22 (2H, t, J = 8.4Hz), 3.80-3.90 (1H, m), 3.85 (3H, s) , 4.10-4.20 (3H, m), 6.85-7.00 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis Calculated as C ₂₉ H ₃₆ N ₂ O ₄ · HCl · 0.5H ₂ O: C, 66.72; H, 7.34; N, 5.37.
Experimental value: C, 66.33; H, 7.54; N, 5.28.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および塩化フェナシル(248mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(301mg) を融点114-116℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.35-1.60 (3H, m), 1.65-1.85 (4H, m), 2.15-2.35 (2H, m), 2.72 (2H, t, J = 7.6Hz), 2.85-3.10 (6H, m), 3.23 (2H, t, J = 8.4Hz), 3.86 (2H, s), 4.14 (2H, t, J = 8.4Hz), 7.40-7.75 (5H, m), 7.98 (1H, s), 8.02 (1H, s).
元素分析 C₂₇H₃₂N₂O₃・HCl・H₂Oとして
計算値：C, 66.58; H, 7.24; N, 5.75.
実験値：C, 66.64; H, 7.25; N, 5.36. 8- {3- [1- (2-oxo-2-phenylethyl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- 4-one hydrochloride

8- [3- (4-piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and phenacyl chloride (248 mg) Using the same procedure as in Example 81, the title compound (301 mg) was obtained as colorless crystals having a melting point of 114-116 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.35-1.60 (3H, m), 1.65-1.85 (4H, m), 2.15-2.35 (2H, m), 2.72 (2H, t, J = 7.6 Hz ), 2.85-3.10 (6H, m), 3.23 (2H, t, J = 8.4Hz), 3.86 (2H, s), 4.14 (2H, t, J = 8.4Hz), 7.40-7.75 (5H, m) , 7.98 (1H, s), 8.02 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₂ N ₂ O ₃ .HCl.H ₂ O: C, 66.58; H, 7.24; N, 5.75.
Experimental value: C, 66.64; H, 7.25; N, 5.36.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) およびスチレンオキシド(193mg) のテトラヒドロフラン(1ml) 混合物を100℃で1時間攪拌した。反応混合物をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル−メタノール(9:1))にて精製し、表題化合物のフリー塩基体を融点133-135℃の無色結晶(468mg)として得た。
上記フリー塩基体(390mg) を塩化水素−エタノール溶液で処理することにより、表題化合物(405mg) を融点235-237℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.30-1.55 (3H, m), 1.60-1.85 (4H, m), 2.00-2.20 (1H, m), 2.25-2.45 (1H, m), 2.50-2.60 (2H, m), 2.72 (2H, t, J = 7.6Hz), 2.85-3.05 (5H, m), 3.15-3.30 (3H, m), 3.40-4.40 (1H, br.), 4.14 (2H, t, J = 8.4Hz), 4.80 (1H, dd, J = 8.4, 5.4Hz), 7.20-7.40 (5H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₂N₂O₃・HCl・0.5H₂Oとして
計算値：C, 67.84; H, 7.17; N, 5.86.
実験値：C, 68.30; H, 7.47; N, 5.72. (±) -8- {3- [1- (2-hydroxy-2-phenylethyl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-4-one hydrochloride

Of 8- [3- (4-piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and styrene oxide (193 mg) Tetrahydrofuran (1 ml) mixture was stirred at 100 ° C. for 1 hour. The reaction mixture was purified by silica gel chromatography (developing solvent; ethyl acetate-methanol (9: 1)) to obtain the free base of the title compound as colorless crystals (468 mg) having a melting point of 133-135 ° C.
The above free base (390 mg) was treated with a hydrogen chloride-ethanol solution to give the title compound (405 mg) as colorless crystals having a melting point of 235-237 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.30-1.55 (3H, m), 1.60-1.85 (4H, m), 2.00-2.20 (1H, m), 2.25-2.45 (1H, m), 2.50 -2.60 (2H, m), 2.72 (2H, t, J = 7.6Hz), 2.85-3.05 (5H, m), 3.15-3.30 (3H, m), 3.40-4.40 (1H, br.), 4.14 ( 2H, t, J = 8.4Hz), 4.80 (1H, dd, J = 8.4, 5.4Hz), 7.20-7.40 (5H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis _{C 27 H 32 N 2 O 3} · HCl · 0.5H 2 O Calculated: C, 67.84; H, 7.17 ; N, 5.86.
Experimental values: C, 68.30; H, 7.47; N, 5.72.

参考例１９１で得た1-(3-アミノ-4-メトキシフェニル)-3-(4-ピペリジニル)-1-プロパノン ２塩酸塩(1.00g) および炭酸カリウム(1.00g) のエタノール(20ml) 懸濁液に1-(2-ブロモエトキシ)-2-エトキシベンゼン(732mg) を室温にて加えた。80℃で12時間攪拌後、反応液を減圧下濃縮した。残査に水(30ml)および酢酸エチル(40ml)を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル−メタノール(9:1))にて精製し、表題化合物のフリー塩基体を融点81-82℃の無色結晶(828mg)として得た。
上記フリー塩基体(200mg) を塩化水素−エタノール溶液で処理することにより、表題化合物(240mg) を融点123-125℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.43 (3H, t, J = 7.0Hz), 1.60-1.80 (4H, m), 2.00-2.20 (2H, m), 2.50-4.50 (2H, br), 2.83 (2H, t, J = 6.2Hz), 2.91 (2H, t, J = 7.2Hz), 2.95-3.10 (2H, m), 3.91 (3H, s), 4.06 (2H, q, J = 7.0Hz), 4.16 (2H, t, J = 6.2Hz), 6.79 (1H, d, J = 8.4Hz), 6.85-6.95 (4H, m), 7.35-7.45 (2H, m).
元素分析 C₂₅H₃₄N₂O₄・2HCl・H₂Oとして
計算値：C, 58.02; H, 7.40; N, 5.41.
実験値：C, 57.66; H, 7.82; N, 4.99. 1- (3-Amino-4-methoxyphenyl) -3- {1- [2- (2-ethoxyphenoxy) ethyl] -4-piperidinyl} -1-propanone dihydrochloride

1- (3-Amino-4-methoxyphenyl) -3- (4-piperidinyl) -1-propanone obtained in Reference Example 191 dihydrochloride (1.00 g) and potassium carbonate (1.00 g) in ethanol (20 ml) To the suspension was added 1- (2-bromoethoxy) -2-ethoxybenzene (732 mg) at room temperature. After stirring at 80 ° C. for 12 hours, the reaction solution was concentrated under reduced pressure. Water (30 ml) and ethyl acetate (40 ml) were added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; ethyl acetate-methanol (9: 1)) to obtain the free base of the title compound as colorless crystals (828 mg) having a melting point of 81-82 ° C.
The above free base (200 mg) was treated with a hydrogen chloride-ethanol solution to give the title compound (240 mg) as colorless crystals having a melting point of 123-125 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.43 (3H, t, J = 7.0 Hz), 1.60-1.80 (4H, m), 2.00-2.20 (2H, m ), 2.50-4.50 (2H, br), 2.83 (2H, t, J = 6.2Hz), 2.91 (2H, t, J = 7.2Hz), 2.95-3.10 (2H, m), 3.91 (3H, s) , 4.06 (2H, q, J = 7.0Hz), 4.16 (2H, t, J = 6.2Hz), 6.79 (1H, d, J = 8.4Hz), 6.85-6.95 (4H, m), 7.35-7.45 ( 2H, m).
Elemental analysis Calculated as C ₂₅ H ₃₄ N ₂ O ₄ · 2HCl · H ₂ O: C, 58.02; H, 7.40; N, 5.41.
Experimental value: C, 57.66; H, 7.82; N, 4.99.

実施例３２７で得た1-(3-アミノ-4-メトキシフェニル)-3-{1-[2-(2-エトキシフェノキシ)エチル]-4-ピペリジニル}-1-プロパノン ２塩酸塩(300mg) およびトリエチルアミン(0.195ml) のテトラヒドロフラン(10ml) 溶液にメタンスルホニルクロリド(0.108ml) を室温にて加え12時間攪拌後、反応液を減圧下濃縮した。残査に水(30ml)および酢酸エチル(40ml)を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル−メタノール(9:1))にて精製し、表題化合物のフリー塩基体を無色油状物(291mg)として得た。
上記フリー塩基体(290mg) を塩化水素−エタノール溶液で処理することにより、表題化合物(277mg) を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.43 (3H, t, J = 7.0Hz), 1.60-1.80 (4H, m), 2.05-2.20 (2H, m), 2.84 (2H, t, J = 6.2Hz), 2.90-3.10 (2H, m), 2.99 (3H,s), 3.45 (3H, s), 3.95-4.20 (7H, m), 6.85-6.95 (4H, m), 6.94 (1H, d, J = 5.6Hz), 7.82 (1H, dd, J = 8.4, 2.2Hz), 8.11 (1H, d, J = 2.2Hz).
元素分析 C₂₆H₃₆N₂O₆S・HCl・1.5H₂Oとして
計算値：C, 54.97; H, 7.10; N, 4.93.
実験値：C, 54.63; H, 6.93; N, 4.57. N- [5- (3- {1- [2- (2-Ethoxyphenoxy) ethyl] -4-piperidinyl} propanoyl) -2-methoxyphenyl] methanesulfonamide hydrochloride

1- (3-Amino-4-methoxyphenyl) -3- {1- [2- (2-ethoxyphenoxy) ethyl] -4-piperidinyl} -1-propanone dihydrochloride (300 mg) obtained in Example 327 To a solution of triethylamine (0.195 ml) in tetrahydrofuran (10 ml) was added methanesulfonyl chloride (0.108 ml) at room temperature and stirred for 12 hours, and then the reaction mixture was concentrated under reduced pressure. Water (30 ml) and ethyl acetate (40 ml) were added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; ethyl acetate-methanol (9: 1)) to obtain the free base of the title compound as a colorless oil (291 mg).
The above free base (290 mg) was treated with a hydrogen chloride-ethanol solution to obtain the title compound (277 mg) as a colorless amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.43 (3H, t, J = 7.0 Hz), 1.60-1.80 (4H, m), 2.05-2.20 (2H, m ), 2.84 (2H, t, J = 6.2Hz), 2.90-3.10 (2H, m), 2.99 (3H, s), 3.45 (3H, s), 3.95-4.20 (7H, m), 6.85-6.95 ( 4H, m), 6.94 (1H, d, J = 5.6Hz), 7.82 (1H, dd, J = 8.4, 2.2Hz), 8.11 (1H, d, J = 2.2Hz).
Elemental analysis Calculated as C ₂₆ H ₃₆ N ₂ O ₆ S · HCl · 1.5H ₂ O: C, 54.97; H, 7.10; N, 4.93.
Experimental value: C, 54.63; H, 6.93; N, 4.57.

実施例３２７で得た1-(3-アミノ-4-メトキシフェニル)-3-{1-[2-(2-エトキシフェノキシ)エチル]-4-ピペリジニル}-1-プロパノン ２塩酸塩(300mg) およびトリエチルアミン(0.195ml) のテトラヒドロフラン(10ml) 溶液に無水酢酸(0.132ml) を室温にて加え12時間攪拌後、反応液を減圧下濃縮した。残査に水(30ml)および酢酸エチル(40ml)を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル−メタノール(9:1))にて精製し、表題化合物のフリー塩基体を無色油状物(276mg)として得た。
上記フリー塩基体(270mg) を塩化水素−エタノール溶液で処理することにより、表題化合物(277mg) を融点127-129℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.43 (3H, t, J = 7.0Hz), 1.60-1.80 (4H, m), 2.05-2.20 (2H, m), 2.23 (3H, s), 2.83 (2H, t, J = 6.2Hz), 2.90-3.10 (4H, m), 3.94 (3H, s), 4.07 (2H, q, J = 7.0Hz), 4.15 (2H, t, J = 6.2Hz), 6.80-7.00 (5H, m), 7.70-7.80 (2H, m), 9.01 (1H, s).
元素分析 C₂₇H₃₆N₂O₅・HCl・0.5H₂Oとして
計算値：C, 63.09; H, 7.45; N, 5.45.
実験値：C, 60.19; H, 7.42; N, 5.22. N- [5- (3- {1- [2- (2-Ethoxyphenoxy) ethyl] -4-piperidinyl} propanoyl) -2-methoxyphenyl] acetamide hydrochloride

1- (3-Amino-4-methoxyphenyl) -3- {1- [2- (2-ethoxyphenoxy) ethyl] -4-piperidinyl} -1-propanone dihydrochloride (300 mg) obtained in Example 327 To a solution of triethylamine (0.195 ml) in tetrahydrofuran (10 ml) was added acetic anhydride (0.132 ml) at room temperature and stirred for 12 hours, and then the reaction mixture was concentrated under reduced pressure. Water (30 ml) and ethyl acetate (40 ml) were added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; ethyl acetate-methanol (9: 1)) to obtain the free base of the title compound as a colorless oil (276 mg).
The above free base (270 mg) was treated with a hydrogen chloride-ethanol solution to give the title compound (277 mg) as colorless crystals having a melting point of 127-129 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.43 (3H, t, J = 7.0 Hz), 1.60-1.80 (4H, m), 2.05-2.20 (2H, m ), 2.23 (3H, s), 2.83 (2H, t, J = 6.2Hz), 2.90-3.10 (4H, m), 3.94 (3H, s), 4.07 (2H, q, J = 7.0Hz), 4.15 (2H, t, J = 6.2Hz), 6.80-7.00 (5H, m), 7.70-7.80 (2H, m), 9.01 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₆ N ₂ O ₅ · HCl · 0.5H ₂ O: C, 63.09; H, 7.45; N, 5.45.
Experimental values: C, 60.19; H, 7.42; N, 5.22.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(700mg)、炭酸カリウム(700mg)、およびヨウ化カリウム(触媒量)のアセトニトリル(10ml) 懸濁液に1-クロロインダン(360mg) を室温にて加え12時間攪拌後、反応液を減圧下濃縮した。残査に水(15ml)および酢酸エチル(20ml)を加え、酢酸エチルで抽出した。抽出液を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥した後、溶媒を減圧下留去した。得られた残渣をシリカゲルクロマトグラフィー(展開溶媒；酢酸エチル−メタノール(9:1))にて精製し、表題化合物のフリー塩基体を融点111-113℃の無色結晶(285mg)として得た。
上記フリー塩基体(270mg) を塩化水素−エタノール溶液で処理することにより、表題化合物(270mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.00-1.45 (3H, m), 1.60-1.80 (4H, m), 2.00-2.30 (4H, m), 2.60-2.95 (8H, m), 3.02 (2H, t, J = 7.5Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 4.35 (1H, t, J = 7.0Hz), 7.15-7.40 (3H, m), 7.60-7.80 (3H, m).
元素分析 C₂₈H₃₂N₂O₂・HCl・2.0H₂Oとして
計算値：C, 67.12; H, 7.44; N, 5.59.
実験値：C, 67.34; H, 7.30; N, 5.45. (±) -8- {3- [1- (2,3-Dihydro-1H-inden-1-yl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3 , 2,1-ij] quinolin-4-one hydrochloride

8- [3- (4-piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (700 mg), potassium carbonate (700 mg), 1-Chloroindane (360 mg) was added to a suspension of potassium iodide (catalytic amount) in acetonitrile (10 ml) at room temperature and stirred for 12 hours, and then the reaction mixture was concentrated under reduced pressure. Water (15 ml) and ethyl acetate (20 ml) were added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (developing solvent; ethyl acetate-methanol (9: 1)) to obtain the free base of the title compound as colorless crystals (285 mg) having a melting point of 111-113 ° C.
The above free base (270 mg) was treated with a hydrogen chloride-ethanol solution to obtain the title compound (270 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.00-1.45 (3H, m), 1.60-1.80 (4H, m), 2.00-2.30 (4H, m), 2.60-2.95 (8H, m), 3.02 (2H, t, J = 7.5Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 4.35 (1H, t, J = 7.0Hz), 7.15-7.40 (3H, m), 7.60-7.80 (3H, m).
Elemental analysis Calculated as C ₂₈ H ₃₂ N ₂ O ₂ · HCl · 2.0H ₂ O: C, 67.12; H, 7.44; N, 5.59.
Experimental value: C, 67.34; H, 7.30; N, 5.45.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および(±)-1-クロロ-1,2,3,4-テトラヒドロナフタレン(280mg) を用いて、実施例３３０と同様の操作を行うことにより、表題化合物(43mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.10-1.45 (3H, m), 1.55-1.80 (6H, m), 1.85-2.10 (4H, m), 2.50-3.10 (10H, m), 3.23 (2H, t, J = 8.4Hz), 3.75-3.85 (1H, m), 4.14 (2H, t, J = 8.4Hz), 7.00-7.20 (3H, m), 7.65-7.75 (3H, m). (±) -8- {3- [1- (1,2,3,4-Tetrahydro-1-naphthalenyl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3 , 2,1-ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and (±) -1- The same operation as in Example 330 was carried out using chloro-1,2,3,4-tetrahydronaphthalene (280 mg) to give the title compound (43 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.10-1.45 (3H, m), 1.55-1.80 (6H, m), 1.85-2.10 (4H, m), 2.50-3.10 (10H, m), 3.23 (2H, t, J = 8.4Hz), 3.75-3.85 (1H, m), 4.14 (2H, t, J = 8.4Hz), 7.00-7.20 (3H, m), 7.65-7.75 (3H, m).

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および(±)-メタンスルホン酸1,2,3,4-テトラヒドロ-2-ナフタレニル(456mg) を用いて、実施例３３０と同様の操作を行うことにより、表題化合物(290mg) を融点223-225℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20-1.45 (3H, m), 1.55-1.85 (4H, m), 2.00-2.40 (3H, m), 2.60-3.10 (14H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.68 (1H, s), 7.73 (1H, s).
元素分析 C₂₉H₃₄N₂O₂・HCl・H₂Oとして
計算値：C, 70.07; H, 7.50; N, 5.64.
実験値：C, 69.77; H, 7.26; N, 5.56. (±) -8- {3- [1- (1,2,3,4-tetrahydro-2-naphthalenyl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3 , 2,1-ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and (±) -methanesulfone Using the acid 1,2,3,4-tetrahydro-2-naphthalenyl (456 mg), the title compound (290 mg) was obtained as colorless crystals having a melting point of 223-225 ° C. by performing the same operation as in Example 330. .
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.20-1.45 (3H, m), 1.55-1.85 (4H, m), 2.00-2.40 (3H, m), 2.60-3.10 (14H, m), 3.23 (2H, t, J = 8.4Hz), 4.14 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.68 (1H, s), 7.73 (1H, s).
Elemental analysis Calculated as C ₂₉ H ₃₄ N ₂ O ₂ · HCl · H ₂ O: C, 70.07; H, 7.50; N, 5.64.
Experimental value: C, 69.77; H, 7.26; N, 5.56.

8-[3-(4-ピペリジニル)プロパノイル]-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) およびメタンスルホン酸6,7,8,9-テトラヒドロ-5H-ベンゾ[a]シクロヘプテン-7-イル(485mg) を用いて、実施例３３０と同様の操作を行うことにより、表題化合物(51mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 300MHz, CDCl₃) δ 1.30-1.60 (5H, m), 1.60-1.85 (4H, m), 2.15-2.50 (4H, m), 2.65-2.95 (11H, m), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.12 (4H, s), 7.67 (1H, s), 7.71 (1H, s). 8- {3- [1- (6,7,8,9-tetrahydro-5H-benzo [a] cyclohepten-7-yl) -4-piperidinyl] propanoyl} -1,2,5,6-tetrahydro-4H -Pyrrolo [3,2,1-ij] quinolin-4-one hydrochloride

8- [3- (4-Piperidinyl) propanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and methanesulfonic acid 6,7 , 8,9-Tetrahydro-5H-benzo [a] cyclohepten-7-yl (485 mg) was used in the same manner as in Example 330 to give the title compound (51 mg) as a pale yellow amorphous powder. Obtained.
¹ H NMR (free base; 300 MHz, CDCl ₃ ) δ 1.30-1.60 (5H, m), 1.60-1.85 (4H, m), 2.15-2.50 (4H, m), 2.65-2.95 (11H, m), 3.02 (2H, t, J = 7.8Hz), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.12 (4H, s), 7.67 (1H, s), 7.71 (1H, s).

参考例１９２で得た8-(3-クロロプロパノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(489mg) およびN-(2,3-ジヒドロ-1H-インデン-2-イル)-N-エチルアミン(330mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(406mg) を融点192-196℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.10 (3H, t, J = 7.2Hz), 2.10-2.45 (1H, m), 2.60-3.30 (16H, m), 3.55-3.75 (1H, m), 4.13 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₅H₂₈N₂O₂・HCl・0.5H₂Oとして
計算値：C, 69.19; H, 6.97; N, 6.46.
実験値：C, 68.65; H, 7.09; N, 6.20. 8- {3- [2,3-dihydro-1H-inden-2-yl (ethyl) amino] propanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- (3-Chloropropanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (489 mg) obtained in Reference Example 192 and N- ( The title compound (406 mg) was purified in the same manner as in Example 9 by using 2,3-dihydro-1H-inden-2-yl) -N-ethylamine (330 mg) to give a colorless compound having a melting point of 192-196 ° C. Obtained as crystals.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.10 (3H, t, J = 7.2 Hz), 2.10-2.45 (1H, m), 2.60-3.30 (16H, m), 3.55-3.75 (1H, m ), 4.13 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₅ H ₂₈ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 69.19; H, 6.97; N, 6.46.
Experimental value: C, 68.65; H, 7.09; N, 6.20.

参考例１７９で得た8-(4-クロロブタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および2,3,4,5-テトラヒドロ-1H-2-ベンズアゼピン(290mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(538mg) を融点230-232℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.60-1.80 (2H, m), 1.90 (2H, quintet, J = 7.2Hz), 2.40 (2H, t, J = 7.2Hz), 2.70 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.20 (2H, t, J = 8.4Hz), 3.87 (2H, s), 4.12 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.66 (1H, s), 7.70 (1H, s).
元素分析 C₂₅H₂₈N₂O₂・HClとして
計算値：C, 70.66; H, 6.88; N, 6.59.
実験値：C, 70.20; H, 6.80; N, 6.56. 8- [4- (1,3,4,5-Tetrahydro-2H-2-benzazepin-2-yl) butanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij ] Quinolin-4-one hydrochloride

8- (4-Chlorobutanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 2,3 obtained in Reference Example 179 , 4,5-Tetrahydro-1H-2-benzazepine (290 mg) was used in the same manner as in Example 9 to obtain the title compound (538 mg) as colorless crystals having a melting point of 230-232 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.60-1.80 (2H, m), 1.90 (2H, quintet, J = 7.2 Hz), 2.40 (2H, t, J = 7.2 Hz), 2.70 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.20 (2H, t, J = 8.4Hz), 3.87 (2H, s), 4.12 (2H, t, J = 8.4Hz), 7.00- 7.20 (4H, m), 7.66 (1H, s), 7.70 (1H, s).
Elemental analysis Calculated as C ₂₅ H ₂₈ N ₂ O ₂ .HCl: C, 70.66; H, 6.88; N, 6.59.
Experimental value: C, 70.20; H, 6.80; N, 6.56.

参考例１７９で得た8-(4-クロロブタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(500mg) および7-メトキシ-2,3,4,5-テトラヒドロ-1H-2-ベンズアゼピン(320mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(246mg) を融点121-123℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.65-1.80 (2H, m), 1.91 (2H, quintet, J = 7.0Hz), 2.42 (2H, t, J = 7.0Hz), 2.71 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.21 (2H, t, J = 8.4Hz), 3.78 (3H, s), 3.84 (2H, s), 4.13 (2H, t, J = 8.4Hz), 6.61 (1H, dd, J = 8.4, 2.6Hz), 6.70 (1H, d, J = 2.6Hz), 7.03 (1H, d, J = 8.4Hz), 7.67 (1H, s), 7.71 (1H, s).
元素分析 C₂₆H₃₀N₂O₃・HCl・H₂Oとして
計算値：C, 66.02; H, 7.03; N, 5.92.
実験値：C, 66.09; H, 7.30; N, 5.64. 8- [4- (7-Methoxy-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl) butanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2 , 1-ij] quinolin-4-one hydrochloride

8- (4-Chlorobutanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (500 mg) and 7-methoxy obtained in Reference Example 179 -23,4,5-Tetrahydro-1H-2-benzazepine (320 mg) was used in the same manner as in Example 9 to give the title compound (246 mg) as colorless crystals having a melting point of 121-123 ° C. Obtained.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.65-1.80 (2H, m), 1.91 (2H, quintet, J = 7.0 Hz), 2.42 (2H, t, J = 7.0 Hz), 2.71 (2H, t, J = 7.6Hz), 2.80-3.15 (8H, m), 3.21 (2H, t, J = 8.4Hz), 3.78 (3H, s), 3.84 (2H, s), 4.13 (2H, t, J = 8.4Hz), 6.61 (1H, dd, J = 8.4, 2.6Hz), 6.70 (1H, d, J = 2.6Hz), 7.03 (1H, d, J = 8.4Hz), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis _{C 26 H 30 N 2 O 3} · HCl · H 2 O Calculated: C, 66.02; H, 7.03 ; N, 5.92.
Experimental value: C, 66.09; H, 7.30; N, 5.64.

参考例１９３で得た(±)-2,3-ジヒドロ-1H-インデン-1-イル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸tert-ブチル(332mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(57mg) を融点98-100℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.50-1.75 (4H, m), 2.00-2.50 (2H, m), 2.54 (2H, t, J = 7.6Hz), 2.75-3.05 (8H, m), 3.12 (2H, t, J = 8.8Hz), 3.94 (2H, t, J = 8.8Hz), 4.60-4.75 (1H, m), 7.20-7.35 (3H, m), 7.60-7.70 (3H, m).
元素分析 C₂₅H₂₈N₂O₂・HCl・1.5H₂Oとして
計算値：C, 66.43; H, 7.14; N, 6.20.
実験値：C, 66.70; H, 6.77; N, 6.09. (±) -8- [5- (2,3-Dihydro-1H-inden-1-ylamino) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

(±) -2,3-Dihydro-1H-inden-1-yl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3] obtained in Reference Example 193 , 2,1-ij] quinolin-8-yl) pentyl] carbamate tert-butyl (332 mg), the same operation as in Example 1 was carried out to give the title compound (57 mg) with a melting point of 98-100 ° C. As colorless crystals.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.50-1.75 (4H, m), 2.00-2.50 (2H, m), 2.54 (2H, t, J = 7.6Hz), 2.75-3.05 (8H, m) , 3.12 (2H, t, J = 8.8Hz), 3.94 (2H, t, J = 8.8Hz), 4.60-4.75 (1H, m), 7.20-7.35 (3H, m), 7.60-7.70 (3H, m ).
Elemental analysis Calculated as C ₂₅ H ₂₈ N ₂ O ₂ · HCl · 1.5H ₂ O: C, 66.43; H, 7.14; N, 6.20.
Experimental value: C, 66.70; H, 6.77; N, 6.09.

参考例１９４で得た2,3-ジヒドロ-1H-インデン-2-イル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸tert-ブチル(461mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物(275mg) を融点187-189℃の無色結晶として得た。
¹H NMR (200MHz, DMSO-d₆) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.40 (12H, m), 3.80-4.05 (3H, m), 7.10-7.30 (4H, m), 7.75 (2H, s), 9.40-9.60 (2H, br).
元素分析 C₂₅H₂₈N₂O₂・HCl・2H₂Oとして
計算値：C, 65.13; H, 7.22; N, 6.08.
実験値：C, 64.75; H, 7.01; N, 6.02. 8- [5- (2,3-Dihydro-1H-inden-2-ylamino) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one Hydrochloride

2,3-Dihydro-1H-inden-2-yl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1] obtained in Reference Example 194 -ij] Quinolin-8-yl) pentyl] carbamate tert-butyl (461 mg) was used in the same manner as in Example 1 to give the title compound (275 mg) as colorless crystals having a melting point of 187-189 ° C. Obtained.
¹ H NMR (200MHz, DMSO-d ₆ ) δ 1.60-1.80 (4H, m), 2.59 (2H, t, J = 7.6Hz), 2.80-3.40 (12H, m), 3.80-4.05 (3H, m) , 7.10-7.30 (4H, m), 7.75 (2H, s), 9.40-9.60 (2H, br).
Elemental analysis Calculated as C ₂₅ H ₂₈ N ₂ O ₂ · HCl · 2H ₂ O: C, 65.13; H, 7.22; N, 6.08.
Experimental value: C, 64.75; H, 7.01; N, 6.02.

参考例1で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および6,7-ジメトキシ-1,2,3,4-テトラヒドロイソキノリン(945mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(430mg) を融点215-217℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.60-2.00 (6H, m), 2.56 (2H, t, J = 7.0Hz), 2.65-3.10 (8H, m), 3.20 (2H, t, J = 8.4Hz), 3.55 (2H, s), 3.84 (6H, s), 4.13 (2H, t, J = 8.4Hz), 6.52 (1H, s), 6.58 (1H, s), 7.68 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₂N₂O₄・HCl・H₂Oとして
計算値：C, 64.47; H, 7.01; N, 5.57.
実験値：C, 64.74; H, 7.25; N, 5.30. 8- [5- (6,7-Dimethoxy-3,4-dihydro-2 (1H) -isoquinolinyl) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] Quinolin-4-one hydrochloride

8- (5-chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 6, Using 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (945 mg), the title compound (430 mg) was obtained as colorless crystals having a melting point of 215 to 217 ° C. by performing the same operation as in Reference Example 19. .
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.60-2.00 (6H, m), 2.56 (2H, t, J = 7.0 Hz), 2.65-3.10 (8H, m), 3.20 (2H, t, J = 8.4Hz), 3.55 (2H, s), 3.84 (6H, s), 4.13 (2H, t, J = 8.4Hz), 6.52 (1H, s), 6.58 (1H, s), 7.68 (1H, s ), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₂ N ₂ O ₄ · HCl · H ₂ O: C, 64.47; H, 7.01; N, 5.57.
Experimental value: C, 64.74; H, 7.25; N, 5.30.

参考例1で得た8-(5-クロロペンタノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(1.00g) および2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン(605mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(703mg) を融点252-254℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.50-1.85 (4H, m), 2.53 (2H, t, J = 7.4Hz), 2.60-3.10 (14H, m), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.68 (1H, s), 7.73 (1H, s). 8- [5- (1,2,4,5-Tetrahydro-3H-3-benzazepin-3-yl) pentanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij ] Quinolin-4-one hydrochloride

8- (5-chloropentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (1.00 g) obtained in Reference Example 1 and 2, The same operation as in Reference Example 19 was carried out using 3,4,5-tetrahydro-1H-3-benzazepine (605 mg) to give the title compound (703 mg) as colorless crystals having a melting point of 252-254 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.50-1.85 (4H, m), 2.53 (2H, t, J = 7.4Hz), 2.60-3.10 (14H, m), 3.22 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.00-7.20 (4H, m), 7.68 (1H, s), 7.73 (1H, s).

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(650mg) およびN-(2,3-ジヒドロ-1H-インデン-2-イル)-N-エチルアミン(330mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(366mg) を融点160-162℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.20 (3H, t, J = 7.2Hz), 1.30-1.85 (6H, m), 2.50-3.30 (13H, m), 3.60-3.80 (4H, m), 4.10 (2H, t, J = 8.4Hz), 7.05-7.25 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
元素分析C₂₅H₃₄N₂O₂・HCl・3.5H₂Oとして
計算値：C, 60.78; H, 8.57; N, 5.67.
実験値：C, 61.16; H, 8.12; N, 5.88. 8- {6- [2,3-dihydro-1H-inden-2-yl (ethyl) amino] hexanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline -4-one hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (650 mg) obtained in Reference Example 2 and N- ( The title compound (366 mg) was purified in the same manner as in Reference Example 19 using 2,3-dihydro-1H-inden-2-yl) -N-ethylamine (330 mg) to give a colorless compound having a melting point of 160-162 ° C. Obtained as crystals.
¹ H NMR (free _{base; 200MHz, CDCl 3) δ 1.20} (3H, t, J = 7.2Hz), 1.30-1.85 (6H, m), 2.50-3.30 (13H, m), 3.60-3.80 (4H, m ), 4.10 (2H, t, J = 8.4Hz), 7.05-7.25 (4H, m), 7.67 (1H, s), 7.71 (1H, s).
Elemental analysis Calculated as C ₂₅ H ₃₄ N ₂ O ₂ · HCl · 3.5H ₂ O: C, 60.78; H, 8.57; N, 5.67.
Experimental value: C, 61.16; H, 8.12; N, 5.88.

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および6,7-ジメトキシ-1,2,3,4-テトラヒドロイソキノリン(432mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(540mg) を融点216-218℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.35-2.05 (8H, m), 2.51 (2H, t, J = 7.6Hz), 2.60-2.85 (4H, m), 2.93 (2H, t, J = 7.6Hz), 3.02 (2H, t, J = 7.6Hz), 3.22 (2H, t, J = 8.4Hz), 3.55 (2H, s), 3.83 (6H, s), 4.13 (2H, t, J = 8.4Hz), 6.52 (1H, s), 6.59 (1H, s), 7.68 (1H, s), 7.72 (1H, s).
元素分析C₂₈H₃₄N₂O₄・HCl・2.5H₂Oとして
計算値：C, 61.81; H, 7.41; N, 5.15.
実験値：C, 62.26; H, 6.99; N, 5.14. 8- [6- (6,7-Dimethoxy-3,4-dihydro-2 (1H) -isoquinolinyl) hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] Quinolin-4-one hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and 6,7 obtained in Reference Example 2 The title compound (540 mg) was obtained as colorless crystals having a melting point of 216 to 218 ° C. by performing the same operation as in Reference Example 19 using -dimethoxy-1,2,3,4-tetrahydroisoquinoline (432 mg).
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.35-2.05 (8H, m), 2.51 (2H, t, J = 7.6 Hz), 2.60-2.85 (4H, m), 2.93 (2H, t, J = 7.6Hz), 3.02 (2H, t, J = 7.6Hz), 3.22 (2H, t, J = 8.4Hz), 3.55 (2H, s), 3.83 (6H, s), 4.13 (2H, t, J = 8.4Hz), 6.52 (1H, s), 6.59 (1H, s), 7.68 (1H, s), 7.72 (1H, s).
Elemental analysis _{C 28 H 34 N 2 O 4} · HCl · 2.5H 2 O Calculated: C, 61.81; H, 7.41 ; N, 5.15.
Experimental value: C, 62.26; H, 6.99; N, 5.14.

参考例２で得た8-(6-ブロモヘキサノイル)-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン(600mg) および2,3,4,5-テトラヒドロ-1H-3-ベンズアゼピン(277mg) を用いて、参考例１９と同様の操作を行うことにより、表題化合物(566mg) を融点222-225℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.30-1.85 (10H, m), 2.49 (2H, t, J = 7.6Hz), 2.60-2.80 (4H, m), 2.85-3.10 (6H, m), 3.21 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.10 (4H, s), 7.67 (1H, s), 7.72 (1H, s).
元素分析 C₂₇H₃₂N₂O₂・HCl・0.5H₂Oとして
計算値：C, 70.19; H, 7.42; N, 6.06.
実験値：C, 70.72; H, 7.13; N, 6.09. 8- [6- (1,2,4,5-Tetrahydro-3H-3-benzazepin-3-yl) hexanoyl] -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1- ij] quinolin-4-one hydrochloride

8- (6-Bromohexanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one (600 mg) and 2,3 obtained in Reference Example 2 , 4,5-Tetrahydro-1H-3-benzazepine (277 mg) was used in the same manner as in Reference Example 19 to give the title compound (566 mg) as colorless crystals with a melting point of 222-225 ° C.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.30-1.85 (10H, m), 2.49 (2H, t, J = 7.6Hz), 2.60-2.80 (4H, m), 2.85-3.10 (6H, m ), 3.21 (2H, t, J = 8.4Hz), 4.13 (2H, t, J = 8.4Hz), 7.10 (4H, s), 7.67 (1H, s), 7.72 (1H, s).
Elemental analysis Calculated as C ₂₇ H ₃₂ N ₂ O ₂ · HCl · 0.5H ₂ O: C, 70.19; H, 7.42; N, 6.06.
Experimental value: C, 70.72; H, 7.13; N, 6.09.

参考例１７６で得た9-(3-ピペリジン-4-イルプロパノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン(326mg) およびメタンスルホン酸2-(2-メチルフェニル)エチル(214mg) を用いて、実施例８１と同様の操作を行うことにより、表題化合物(172mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 1.94-2.02 (4H, m), 2.32 (3H, s), 2.49-2.53 (2H, m), 2.68 (2H, t, J = 7Hz), 2.80-2.86 (4H, m), 2.94 (4H, t, J = 7Hz), 3.04 (2H, t, J = 11Hz), 3.89(2H, t, J = 6Hz), 7.09-7.15 (4H, m), 7.62 (2H, d, J = 5Hz).
IR (neat) νcm^-1: 1674, 1604, 1489, 1361, 1339, 1168. 9- (3- {1- [2- (2-methylphenyl) ethyl] piperidin-4-yl} propanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1- ij] quinolin-5-one hydrochloride

9- (3-Piperidin-4-ylpropanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one obtained in Reference Example 176 ( 326 mg) and 2- (2-methylphenyl) ethyl methanesulfonate (214 mg) were used in the same manner as in Example 81 to obtain the title compound (172 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.30-1.40 (3H, m), 1.68-1.78 (4H, m), 1.94-2.02 (4H, m), 2.32 (3H, s), 2.49-2.53 (2H, m), 2.68 (2H, t, J = 7Hz), 2.80-2.86 (4H, m), 2.94 (4H, t, J = 7Hz), 3.04 (2H, t, J = 11Hz), 3.89 ( 2H, t, J = 6Hz), 7.09-7.15 (4H, m), 7.62 (2H, d, J = 5Hz).
IR (neat) νcm ^-1 : 1674, 1604, 1489, 1361, 1339, 1168.

参考例５で得た9-(5-クロロペンタノイル)-2,3,6,7-テトラヒドロ-1H,5H-ピリド[3,2,1-ij]キノリン-5-オン(306mg) およびN-[2-(3-フルオロフェニル)エチル]-N-メチルアミン(337mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(205mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.54-1.60 (2H, m), 1.70-1.77 (2H, m), 1.93-1.99 (2H, m), 2.29 (3H, s), 2.44 (2H, t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.67 (2H, t, J = 6Hz), 2.74-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 2.91-2.96 (4H, m), 3.89 (2H, t, J = 6Hz), 6.85-6.91 (2H, m), 6.96 (1H, d, J = 7.5Hz), 7.19-7.25 (1H, m), 7.62 (2H, d, J = 5Hz).
IR (neat) νcm^-1: 1675, 1604, 1589, 1485, 1362, 1339, 1161. 9- {5-[[2- (3-Fluorophenyl) ethyl] (methyl) amino] pentanoyl} -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinoline -5-one hydrochloride

9- (5-Chloropentanoyl) -2,3,6,7-tetrahydro-1H, 5H-pyrido [3,2,1-ij] quinolin-5-one (306 mg) and N obtained in Reference Example 5 The title compound (205 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using-[2- (3-fluorophenyl) ethyl] -N-methylamine (337 mg). It was.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.60 (2H, m), 1.70-1.77 (2H, m), 1.93-1.99 (2H, m), 2.29 (3H, s), 2.44 (2H , t, J = 7.5Hz), 2.58-2.62 (2H, m), 2.67 (2H, t, J = 6Hz), 2.74-2.79 (2H, m), 2.84 (2H, t, J = 6Hz), 2.91 -2.96 (4H, m), 3.89 (2H, t, J = 6Hz), 6.85-6.91 (2H, m), 6.96 (1H, d, J = 7.5Hz), 7.19-7.25 (1H, m), 7.62 (2H, d, J = 5Hz).
IR (neat) νcm ^-1 : 1675, 1604, 1589, 1485, 1362, 1339, 1161.

参考例３４５で得た5-オキソ-5-(2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)ペンチル(2-フェニルエチル)カルバミン酸tert-ブチル (520mg) を用いて、実施例1と同様の操作を行うことにより、表題化合物を融点200-202℃の無色結晶(390mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.64-1.76 (4H, m), 2.47-2.51 (2H, m), 2.93-3.02 (8H, m), 3.05-3.15 (2H, m), 6.97 (1H, d, J = 8.3Hz), 7.22-7.27 (3H, m), 7.31-7.35 (2H, m), 7.78-7.82 (2H, m), 9.25 (2H, s), 10.46 (1H, s).
IR (KBr) νcm^-1: 3305, 2937, 2775, 1684, 1604, 1508, 1367. 6- {5-[(2-Phenylethyl) amino] pentanoyl} -3,4-dihydroquinolin-2 (1H) -one hydrochloride

Using tert-butyl 5-oxo-5- (2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) pentyl (2-phenylethyl) carbamate (520 mg) obtained in Reference Example 345 The title compound was obtained as colorless crystals (390 mg) having a melting point of 200-202 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.64-1.76 (4H, m), 2.47-2.51 (2H, m), 2.93-3.02 (8H, m), 3.05-3.15 (2H, m), 6.97 ( 1H, d, J = 8.3Hz), 7.22-7.27 (3H, m), 7.31-7.35 (2H, m), 7.78-7.82 (2H, m), 9.25 (2H, s), 10.46 (1H, s) .
^{IR (KBr) νcm -1: 3305} , 2937, 2775, 1684, 1604, 1508, 1367.

参考例１９７で得た2-(2-メトキシフェニル)エチル[5-オキソ-5-(2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)ペンチル]カルバミン酸tert-ブチル(630mg) を用いて、実施例1と同様の操作を行うことにより、表題化合物を融点176-177℃の無色結晶(449mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.63-1.72 (4H, m), 2.47-2.51 (2H, m), 2.92-3.01(10H, m), 3.79 (3H, s), 6.90 (1H, t, J = 7.5Hz), 6.98 (2H, t, J = 7.3Hz), 7.18 (1H, d, J = 7.3Hz), 7.24 (1H, t, J = 7.5Hz), 7.78-7.82 (2H, m), 9.16 (2H, s), 10.46 (1H, s).
IR (KBr) νcm^-1: 3272, 2942, 2747, 1682, 1602, 1501, 1369, 1312, 1253, 762. 6- (5-{[2- (2-Methoxyphenyl) ethyl] amino} pentanoyl) -3,4-dihydroquinolin-2 (1H) -one hydrochloride

Tert-Butyl 2- (2-methoxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) pentyl] carbamate obtained in Reference Example 197 ( The title compound was obtained as colorless crystals (449 mg) with a melting point of 176-177 ° C. by carrying out the same operation as in Example 1 using 630 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.63-1.72 (4H, m), 2.47-2.51 (2H, m), 2.92-3.01 (10H, m), 3.79 (3H, s), 6.90 (1H, t, J = 7.5Hz), 6.98 (2H, t, J = 7.3Hz), 7.18 (1H, d, J = 7.3Hz), 7.24 (1H, t, J = 7.5Hz), 7.78-7.82 (2H, m), 9.16 (2H, s), 10.46 (1H, s).
IR (KBr) νcm ^-1 : 3272, 2942, 2747, 1682, 1602, 1501, 1369, 1312, 1253, 762.

参考例１９８で得た2-(2-クロロフェニル)エチル[5-オキソ-5-(2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)ペンチル]カルバミン酸tert-ブチル(670mg) を用いて、実施例1と同様の操作を行うことにより、表題化合物を融点197-198℃の無色結晶(450mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.64-1.74 (4H, m), 2.47-2.51 (2H, m), 2.92-3.10(10H, m), 6.96 (1H, d, J = 8.3Hz), 7.28-7.35 (2H, m), 7.39-7.47 (2H, m), 7.78-7.82 (2H, m), 9.31 (2H, s), 10.45 (1H, s).
IR (KBr) νcm^-1: 3276, 2955, 2738, 1684, 1654, 1599, 1508, 1361, 1304, 1170, 756. 6- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -3,4-dihydroquinolin-2 (1H) -one hydrochloride

Tert-Butyl 2- (2-chlorophenyl) ethyl [5-oxo-5- (2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) pentyl] carbamate (670 mg) obtained in Reference Example 198 ) To give the title compound as colorless crystals (450 mg) with a melting point of 197-198 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.64-1.74 (4H, m), 2.47-2.51 (2H, m), 2.92-3.10 (10H, m), 6.96 (1H, d, J = 8.3Hz) , 7.28-7.35 (2H, m), 7.39-7.47 (2H, m), 7.78-7.82 (2H, m), 9.31 (2H, s), 10.45 (1H, s).
IR (KBr) νcm ^-1 : 3276, 2955, 2738, 1684, 1654, 1599, 1508, 1361, 1304, 1170, 756.

参考例１９５で得た6-(5-クロロペンタノイル)-3,4-ジヒドロキノリン-2(1H)-オン(133mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(187mg)を用いて、実施例９と同様の操作を行うことにより、表題化合物を融点167-168℃の無色結晶(99mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.54-1.61 (2H, m), 1.71-1.79 (2H, m), 2.34 (3H, s), 2.47 (2H, t, J = 7.3Hz), 2.59-2.63 (2H, m), 2.68 (2H, t, J = 8Hz), 2.88-2.97 (4H, m), 3.04 (2H, t, J = 7.3Hz), 6.85 (1H, d, J = 6.4Hz), 7.10-7.19 (2H, m), 7.23 (1H, d, J = 7.5Hz), 7.32 (1H, d, J = 7.5Hz), 7.80 (1H, d, J = 6.4Hz), 7.81 (1H, s), 8.95 (1H, br).
IR (KBr) νcm^-1: 3188, 3059, 1674, 1608, 1595, 1384, 1314, 816, 751. 6- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -3,4-dihydroquinolin-2 (1H) -one hydrochloride

6- (5-Chloropentanoyl) -3,4-dihydroquinolin-2 (1H) -one (133 mg) and N- [2- (2-chlorophenyl) ethyl] -N-methylamine obtained in Reference Example 195 (187 mg) was used for the same operation as in Example 9 to give the title compound as colorless crystals (99 mg) with a melting point of 167-168 ° C.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.61 (2H, m), 1.71-1.79 (2H, m), 2.34 (3H, s), 2.47 (2H, t, J = 7.3 Hz), 2.59-2.63 (2H, m), 2.68 (2H, t, J = 8Hz), 2.88-2.97 (4H, m), 3.04 (2H, t, J = 7.3Hz), 6.85 (1H, d, J = 6.4 Hz), 7.10-7.19 (2H, m), 7.23 (1H, d, J = 7.5Hz), 7.32 (1H, d, J = 7.5Hz), 7.80 (1H, d, J = 6.4Hz), 7.81 ( 1H, s), 8.95 (1H, br).
IR (KBr) νcm ^-1 : 3188, 3059, 1674, 1608, 1595, 1384, 1314, 816, 751.

参考例１９９で得た6-(6-ブロモヘキサノイル)-3,4-ジヒドロキノリン-2(1H)-オン(486mg)および2-フェニルエチルアミン(454mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物を融点223-224℃の無色結晶(205mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.35-1.42 (2H, m), 1.46 (1H, br.s), 1.49-1.56(2H, m), 1.69-1.77(2H, m), 2.62-2.70 (4H, m), 2.80 (2H, t, J = 6Hz), 2.86-2.92 (4H, m), 3.03 (2H, t, J = 7.4Hz), 6.83 (1H, d, J = 7Hz), 7.16-7.18 (3H, m), 7.27-7.31 (2H, m), 7.79 (1H, d, J = 7Hz), 7.80 (1H, s), 8.93 (1H, br).
IR (KBr) νcm^-1: 3193, 3062, 1671, 1605, 1505, 1381, 1314. 6- {6-[(2-Phenylethyl) amino] hexanoyl} -3,4-dihydroquinolin-2 (1H) -one hydrochloride

Using 6- (6-bromohexanoyl) -3,4-dihydroquinolin-2 (1H) -one (486 mg) and 2-phenylethylamine (454 mg) obtained in Reference Example 199, the same as in Example 9 By performing the operation, the title compound was obtained as colorless crystals (205 mg) having a melting point of 223-224 ° C.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.35-1.42 (2H, m), 1.46 (1H, br.s), 1.49-1.56 (2H, m), 1.69-1.77 (2H, m), 2.62 -2.70 (4H, m), 2.80 (2H, t, J = 6Hz), 2.86-2.92 (4H, m), 3.03 (2H, t, J = 7.4Hz), 6.83 (1H, d, J = 7Hz) , 7.16-7.18 (3H, m), 7.27-7.31 (2H, m), 7.79 (1H, d, J = 7Hz), 7.80 (1H, s), 8.93 (1H, br).
IR (KBr) νcm ^-1 : 3193, 3062, 1671, 1605, 1505, 1381, 1314.

参考例１９９で得た6-(6-ブロモヘキサノイル)-3,4-ジヒドロキノリン-2(1H)-オン(486mg)および 2-(2-メトキシフェニル)エチルアミン(567mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物を融点223-224℃の無色結晶(122mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.35-1.43 (2H, m), 1.49-1.57 (2H, m), 1.53 (1H, br), 1.69-1.77(2H, m), 2.62-2.69 (4H, m), 2.78-2.86 (4H, m), 2.90 (2H, t, J = 7Hz), 3.03 (2H, t, J = 7Hz), 3.81 (3H, s), 6.81-6.89 (3H, m), 7.13-7.20 (2H, m), 7.78 (1H, d, J = 7Hz), 7.79 (1H, s), 9.30 (1H, br).
IR (KBr) νcm^-1: 3192, 3061, 1677, 1608, 1495, 1367, 1317, 1243. 6- (6-{[2- (2-Methoxyphenyl) ethyl] amino} hexanoyl) -3,4-dihydroquinolin-2 (1H) -one hydrochloride

Using 6- (6-bromohexanoyl) -3,4-dihydroquinolin-2 (1H) -one (486 mg) and 2- (2-methoxyphenyl) ethylamine (567 mg) obtained in Reference Example 199 The title compound was obtained as colorless crystals (122 mg) having a melting point of 223-224 ° C. by carrying out the same operation as in Example 9.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.35-1.43 (2H, m), 1.49-1.57 (2H, m), 1.53 (1H, br), 1.69-1.77 (2H, m), 2.62-2.69 (4H, m), 2.78-2.86 (4H, m), 2.90 (2H, t, J = 7Hz), 3.03 (2H, t, J = 7Hz), 3.81 (3H, s), 6.81-6.89 (3H, m), 7.13-7.20 (2H, m), 7.78 (1H, d, J = 7Hz), 7.79 (1H, s), 9.30 (1H, br).
IR (KBr) νcm ^-1 : 3192, 3061, 1677, 1608, 1495, 1367, 1317, 1243.

参考例１９９で得た6-(6-ブロモヘキサノイル)-3,4-ジヒドロキノリン-2(1H)-オン(486mg)および 2-(2-クロロフェニル)エチルアミン(584mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物を融点213-214℃の無色結晶(196mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.37-1.45 (2H, m), 1.49 (1H, br), 1.51-1.58(2H, m), 1.71-1.78 (2H, m), 2.65-2.70 (4H, m), 2.86-2.96 (6H, m), 3.04 (2H, t, J = 7Hz), 6.85 (1H, d, J = 7Hz), 7.12-7.31 (3H, m), 7.34 (1H, d, J = 7.4Hz), 7.80 (1H, d, J = 7Hz), 7.81 (1H, s), 8.93 (1H, br).
IR (KBr) νcm^-1: 3191, 3059, 1672, 1608, 1506, 1380, 1316. 6- (6-{[2- (2-Chlorophenyl) ethyl] amino} hexanoyl) -3,4-dihydroquinolin-2 (1H) -one hydrochloride

Example 6 Using 6- (6-bromohexanoyl) -3,4-dihydroquinolin-2 (1H) -one (486 mg) and 2- (2-chlorophenyl) ethylamine (584 mg) obtained in Reference Example 199, The same operation as in 9 was performed to give the title compound as colorless crystals (196 mg) having a melting point of 213 to 214 ° C.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.37-1.45 (2H, m), 1.49 (1H, br), 1.51-1.58 (2H, m), 1.71-1.78 (2H, m), 2.65-2.70 (4H, m), 2.86-2.96 (6H, m), 3.04 (2H, t, J = 7Hz), 6.85 (1H, d, J = 7Hz), 7.12-7.31 (3H, m), 7.34 (1H, d, J = 7.4Hz), 7.80 (1H, d, J = 7Hz), 7.81 (1H, s), 8.93 (1H, br).
IR (KBr) νcm ^-1 : 3191, 3059, 1672, 1608, 1506, 1380, 1316.

参考例２００で得た2-(2-メトキシフェニル)エチル[5-(1-メチル-2-オキソ-1,2,3,4-テトラヒドロキノリン-6-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(220mg) を用いて、実施例1と同様の操作を行うことにより、表題化合物を融点167-168℃の無色結晶(184mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.52-1.68 (4H, m), 2.49 (2H, t, J = 8Hz), 2.83-2.96(10H, m), 3.19 (3H, s), 3.71 (3H, s), 6.81 (1H, t, J = 7.5Hz), 6.90 (1H, t, J = 8.3Hz), 7.08-7.11 (2H, m), 7.16 (1H, d, J = 7.5Hz), 7.76 (1H, s), 7.80 (1H, d, J = 8.3Hz), 9.10 (2H, s).
IR (KBr) νcm^-1: 2951, 2783, 2453, 1688, 1606, 1494, 1469, 1354, 1248, 1125, 766. 6- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one hydrochloride

2- (2-Methoxyphenyl) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl) -5-oxopentyl] carbamic acid obtained in Reference Example 200 The same operation as in Example 1 was carried out using tert-butyl (220 mg) to give the title compound as colorless crystals (184 mg) having a melting point of 167-168 ° C.
^{1 H NMR (400MHz, DMSO-} d 6) δ 1.52-1.68 (4H, m), 2.49 (2H, t, J = 8Hz), 2.83-2.96 (10H, m), 3.19 (3H, s), 3.71 ( 3H, s), 6.81 (1H, t, J = 7.5Hz), 6.90 (1H, t, J = 8.3Hz), 7.08-7.11 (2H, m), 7.16 (1H, d, J = 7.5Hz), 7.76 (1H, s), 7.80 (1H, d, J = 8.3Hz), 9.10 (2H, s).
IR (KBr) νcm ^-1 : 2951, 2783, 2453, 1688, 1606, 1494, 1469, 1354, 1248, 1125, 766.

参考例２０１で得た2-(2-クロロフェニル)エチル[5-(1-メチル-2-オキソ-1,2,3,4-テトラヒドロ-6-キノリニル)-5-オキソペンチル]カルバミン酸tert-ブチル(240mg) を用いて、実施例1と同様の操作を行うことにより、表題化合物を融点102-103℃の無色結晶(193mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.52-1.68 (4H, m), 2.49 (2H, t, J = 8Hz), 2.87-3.07(10H, m), 3.19 (3H, s), 7.10 (1H, d, J = 8.5Hz), 7.19-7.26 (2H, m), 7.32 (1H, dd, J = 7, 2Hz), 7.37 (1H, dd, J = 7, 2Hz), 7.76 (1H, s), 7.81 (1H, d, J = 8.5Hz), 9.25 (2H, s).
IR (KBr) νcm^-1: 2947, 2768, 2453, 1671, 1604, 1477, 1443, 1355, 1126, 751. 6- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -3,4-dihydroquinolin-2 (1H) -one hydrochloride

2- (2-Chlorophenyl) ethyl [5- (1-methyl-2-oxo-1,2,3,4-tetrahydro-6-quinolinyl) -5-oxopentyl] carbamic acid tert- obtained in Reference Example 201 The same operation as in Example 1 was carried out using butyl (240 mg) to give the title compound as colorless crystals (193 mg) having a melting point of 102-103 ° C.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.52-1.68 (4H, m), 2.49 (2H, t, J = 8Hz), 2.87-3.07 (10H, m), 3.19 (3H, s), 7.10 ( 1H, d, J = 8.5Hz), 7.19-7.26 (2H, m), 7.32 (1H, dd, J = 7, 2Hz), 7.37 (1H, dd, J = 7, 2Hz), 7.76 (1H, s ), 7.81 (1H, d, J = 8.5Hz), 9.25 (2H, s).
IR (KBr) νcm ^-1 : 2947, 2768, 2453, 1671, 1604, 1477, 1443, 1355, 1126, 751.

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン (224mg) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(291mg)を用いて、実施例９と同様の操作を行うことにより、表題化合物を淡黄色非晶状粉末 (165mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.55-1.62 (2H, m), 1.72-1.80(2H, m), 2.32 (3H, s) 2.46 (2H, t, J = 7.3Hz), 2.55-2.59 (2H, m), 2.68 (2H, t, J = 7.5Hz), 2.76-2.81 (2H, m), 2.93-2.98 (4H, m), 3.38 (3H, s), 3.81 (3H, s), 6.82-6.90 (2H, m), 7.01 (1H, d, J = 8.5Hz), 7.12-7.19 (2H, m), 7.79 (1H, d, J = 2Hz), 7.87 (1H, dd, J = 8.5, 2Hz).
IR (KBr) νcm^-1: 2941, 1679, 1604, 1495, 1466, 1354, 1243, 1126. 6- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -1-methyl-3,4-dihydroquinolin-2 (1H) -one hydrochloride

6- (5-Chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (224 mg) and N- [2- (2-methoxyphenyl) ethyl] obtained in Reference Example 154 The title compound was obtained as a pale-yellow amorphous powder (165 mg) by conducting the same operation as in Example 9 using -N-methylamine (291 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.55-1.62 (2H, m), 1.72-1.80 (2H, m), 2.32 (3H, s) 2.46 (2H, t, J = 7.3Hz), 2.55 -2.59 (2H, m), 2.68 (2H, t, J = 7.5Hz), 2.76-2.81 (2H, m), 2.93-2.98 (4H, m), 3.38 (3H, s), 3.81 (3H, s ), 6.82-6.90 (2H, m), 7.01 (1H, d, J = 8.5Hz), 7.12-7.19 (2H, m), 7.79 (1H, d, J = 2Hz), 7.87 (1H, dd, J = 8.5, 2Hz).
IR (KBr) νcm ^-1 : 2941, 1679, 1604, 1495, 1466, 1354, 1243, 1126.

参考例１５４で得た6-(5-クロロペンタノイル)-1-メチル-3,4-ジヒドロキノリン-2(1H)-オン(224mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(299mg)を用いて、実施例９と同様の操作を行うことにより、表題化合物を融点129-130℃の無色結晶(200mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.54-1.62 (2H, m), 1.72-1.79 (2H, m), 2.33 (3H, s) 2.47 (2H, t, J = 7.3Hz), 2.59-2.63 (2H, m), 2.68 (2H, t, J = 7.3Hz), 2.88-2.99 (6H, m), 3.39 (3H, s), 7.02 (1H, d, J = 8.5Hz), 7.10-7.19 (2H, m), 7.23 (1H, dd, J = 7.3, 2Hz), 7.32 (1H, dd, J = 8, 2Hz), 7.79 (1H, d, J = 2Hz), 7.87 (1H, dd, J = 8.5, 2Hz).
IR (KBr) νcm^-1: 2943, 1679, 1605, 1474, 1354, 1305, 1126. 6- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -1-methyl-3,4-dihydroquinolin-2 (1H) -one hydrochloride

6- (5-Chloropentanoyl) -1-methyl-3,4-dihydroquinolin-2 (1H) -one (224 mg) and N- [2- (2-chlorophenyl) ethyl]-obtained in Reference Example 154 The title compound was obtained as colorless crystals (200 mg) having a melting point of 129-130 ° C. by conducting the same operation as in Example 9 using N-methylamine (299 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.62 (2H, m), 1.72-1.79 (2H, m), 2.33 (3H, s) 2.47 (2H, t, J = 7.3Hz), 2.59 -2.63 (2H, m), 2.68 (2H, t, J = 7.3Hz), 2.88-2.99 (6H, m), 3.39 (3H, s), 7.02 (1H, d, J = 8.5Hz), 7.10- 7.19 (2H, m), 7.23 (1H, dd, J = 7.3, 2Hz), 7.32 (1H, dd, J = 8, 2Hz), 7.79 (1H, d, J = 2Hz), 7.87 (1H, dd, J = 8.5, 2Hz).
IR (KBr) νcm ^-1 : 2943, 1679, 1605, 1474, 1354, 1305, 1126.

100mlの４口フラスコにポリりん酸7.8gを仕込み、50-60℃に加温したのち1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-4-オン520mg(3mmol) 及び参考例２０２で得た(±)-5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]ヘキサン酸850mg(3.3mmol)を加えた。外温110℃で15時間攪拌後、氷水(20ml) を加えて溶解し8N-NaOH(約20ml) を加えてPH7-8とした。遊離した油状物を酢酸エチル(30ml) で抽出し、水及び飽和食塩水各(20ml) で順次洗浄ののち、MgSO₄乾燥ののち濃縮した。残渣をカラム精製し（塩基性シリカゲル：80g使用,展開溶媒：酢酸エチル-ヘキサン＝1:1）表題化合物のフリー塩基体を淡黄色油状物(660mg) として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 0.95(3H, d, J = 6.6Hz), 1.30-1.37 (1H, m), 1.50-1.59 (1H, m), 1.68-1.76 (2H, m), 2.30 (3H, s), 2.50-2.58 (1H, m), 2.61-2.73 (4H, m), 2.84-2.89 (4H, m), 3.02(2H, t, J = 7.6Hz), 3.22 (2H, t, J = 8.3Hz), 4.13 (2H, t, J = 7.0Hz), 7.08-7.18 (2H, m), 7.23(1H, dd, J = 7.8, 1.5Hz), 7.30 (1H, dd, J = 7.8, 1.5Hz), 7.67 (1H, s), 7.72 (1H, s).
IR (neat) νcm^-1: 1674, 1598, 1494, 1447, 1381, 1330, 1155, 753.
上記で得たフリー塩基体(650mg) を酢酸エチル(1ml) に溶解し、室温下4N-塩酸（酢酸エチル溶液）(0.5ml) を加えた。室温で30分間攪拌後濃縮し、残渣に酢酸エチル(2ml) を加え析出した結晶をろ取し、表題化合物(568mg) を融点93-95℃の微黄色粉末状として得た。 (±) -8- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] hexanoyl} -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] Quinolin-4-one hydrochloride

7.8 g of polyphosphoric acid was charged into a 100 ml 4-neck flask, heated to 50-60 ° C, and then 1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinolin-4-one 520 mg (3 mmol) and 850 mg (3.3 mmol) of (±) -5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] hexanoic acid obtained in Reference Example 202 were added. After stirring at an external temperature of 110 ° C. for 15 hours, ice water (20 ml) was added and dissolved, and 8N-NaOH (about 20 ml) was added to obtain PH7-8. The liberated oil was extracted with ethyl acetate (30 ml), washed successively with water and saturated brine (20 ml), dried over MgSO _{4 and} concentrated. The residue was purified by column (basic silica gel: 80 g, developing solvent: ethyl acetate-hexane = 1: 1) to give the free base of the title compound as a pale yellow oil (660 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 0.95 (3H, d, J = 6.6 Hz), 1.30-1.37 (1H, m), 1.50-1.59 (1H, m), 1.68-1.76 (2H, m ), 2.30 (3H, s), 2.50-2.58 (1H, m), 2.61-2.73 (4H, m), 2.84-2.89 (4H, m), 3.02 (2H, t, J = 7.6Hz), 3.22 ( 2H, t, J = 8.3Hz), 4.13 (2H, t, J = 7.0Hz), 7.08-7.18 (2H, m), 7.23 (1H, dd, J = 7.8, 1.5Hz), 7.30 (1H, dd , J = 7.8, 1.5Hz), 7.67 (1H, s), 7.72 (1H, s).
IR (neat) νcm ^-1 : 1674, 1598, 1494, 1447, 1381, 1330, 1155, 753.
The free base (650 mg) obtained above was dissolved in ethyl acetate (1 ml), and 4N hydrochloric acid (ethyl acetate solution) (0.5 ml) was added at room temperature. The mixture was stirred at room temperature for 30 minutes and concentrated. Ethyl acetate (2 ml) was added to the residue, and the precipitated crystals were collected by filtration to give the title compound (568 mg) as a slightly yellow powder having a melting point of 93-95 ° C.

5,6-ジヒドロ-4H-ピロロ[3,2,1-ij]キノリン2(1H)-オン520mg(3mmol) 及び参考例２０２で得た(±)-5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]ヘキサン酸850mg(3.3mmol) を用いて、実施例３５７と同様の操作を行うことにより、表題化合物のフリー塩基体を淡黄色油状物(456mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 0.96 (3H, d, J = 6.4Hz), 1.30-1.37 (1H, m), 1.52-1.60(1H, m), 1.68-1.77 (2H, m), 2.00-2.06 (2H, m), 2.31(3H, s), 2.52-2.59 (1H, m), 2.62-2.75 (2H, m), 2.81-2.90 (6H, m), 3.54 (2H, s), 3.74 (2H, t, J = 6.0Hz), 7.10 (1H, dt, J = 7.3, 1.7Hz), 7.16 (1H, dt, J = 7.3, 1.7Hz), 7.23 (1H, dd, J = 7.6, 1.7Hz), 7.30 (1H, dd, J = 7.6, 1.7Hz), 7.73 (2H, s).
IR (neat) νcm^-1: 1718, 1673, 1604, 1496, 1343, 1154, 753.
上記で得たフリー塩基体(440mg) を酢酸エチル(1ml) に溶解し、室温下4N-塩酸（酢酸エチル溶液）(0.5ml) を加えた。室温で30分間攪拌後濃縮し、残渣に酢酸エチル(2ml) を加え析出した結晶をろ取し、表題化合物(420mg)を融点63-65℃の微黄色粉末状として得た。 (±) -8- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] hexanoyl} -5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline-2 ( 1H) -one hydrochloride

5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin 2 (1H) -one 520 mg (3 mmol) and (±) -5-[[2- (2-chlorophenyl) obtained in Reference Example 202 ) Ethyl] (methyl) amino] hexanoic acid 850 mg (3.3 mmol) was used in the same manner as in Example 357 to give the free base of the title compound as a pale yellow oil (456 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 0.96 (3H, d, J = 6.4 Hz), 1.30-1.37 (1H, m), 1.52-1.60 (1H, m), 1.68-1.77 (2H, m ), 2.00-2.06 (2H, m), 2.31 (3H, s), 2.52-2.59 (1H, m), 2.62-2.75 (2H, m), 2.81-2.90 (6H, m), 3.54 (2H, s ), 3.74 (2H, t, J = 6.0Hz), 7.10 (1H, dt, J = 7.3, 1.7Hz), 7.16 (1H, dt, J = 7.3, 1.7Hz), 7.23 (1H, dd, J = 7.6, 1.7Hz), 7.30 (1H, dd, J = 7.6, 1.7Hz), 7.73 (2H, s).
IR (neat) νcm ^-1 : 1718, 1673, 1604, 1496, 1343, 1154, 753.
The free base (440 mg) obtained above was dissolved in ethyl acetate (1 ml), and 4N hydrochloric acid (ethyl acetate solution) (0.5 ml) was added at room temperature. The mixture was stirred at room temperature for 30 minutes and concentrated. Ethyl acetate (2 ml) was added to the residue, and the precipitated crystals were collected by filtration to give the title compound (420 mg) as a slightly yellow powder with a melting point of 63-65 ° C.

1,3-ジメチル-1,3-ジヒドロ-2H-ベンゾイミダゾール-2-オン484mg(3mmol)及び参考例２０２で得た(±)-5-[[2-(2-クロロフェニル)エチル](メチル)アミノ]ヘキサン酸850mg(3.3mmol)を用いて、実施例 と同様の操作を行うことにより、表題化合物(860mg) のフリー塩基体を淡黄色油状物として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 0.96(3H, d, J = 6.46Hz), 1.32-1.39 (1H, m), 1.54-1.59
(1H,m), 1.71-1.77 (2H, m), 2.31(3H, s), 2.51-2.58 (1H, m), 2.61-2.75 (2H, m), 2.82-2.99 (4H, m), 3.45 (3H, s), 3.46 (3H, s), 6.99 (1H, d, J = 8.3Hz), 7.09 (1H, dt, J = 7.3, 1.7Hz), 7.15 (1H, dt, J = 7.3, 1.7Hz), 7.23 (1H, dd, J = 7.6, 1.7Hz), 7.30 (1H, dd, J = 7.6, 1.7Hz), 7.62 (1H, d, J = 1.5Hz), 7.78 (1H, dd, J = 8.3, 1.5Hz).
IR (KBr) νcm^-1: 1720, 1676, 1622, 1511, 1475, 1395, 1195, 750, 584
上記で得たフリー塩基体(850mg) を酢酸エチル(2ml) に溶解し、室温下4N-塩酸（酢酸エチル溶液）(0.5ml) を加えた。室温で30分間攪拌後濃縮し、残渣に酢酸エチル(2ml) を加え析出した結晶をろ取し、表題化合物(900mg)を微黄色非晶状粉末として得た。 (±) -1,3-Dimethyl-5- {5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] hexanoyl} -1,3-dihydro-2H-benzimidazol-2-one hydrochloride

1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2-one 484 mg (3 mmol) and (±) -5-[[2- (2-chlorophenyl) ethyl] (methyl) obtained in Reference Example 202 ) Amino] hexanoic acid 850 mg (3.3 mmol) was used in the same manner as in Example to give the free base of the title compound (860 mg) as a pale yellow oil.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 0.96 (3H, d, J = 6.46 Hz), 1.32-1.39 (1H, m), 1.54-1.59
(1H, m), 1.71-1.77 (2H, m), 2.31 (3H, s), 2.51-2.58 (1H, m), 2.61-2.75 (2H, m), 2.82-2.99 (4H, m), 3.45 (3H, s), 3.46 (3H, s), 6.99 (1H, d, J = 8.3Hz), 7.09 (1H, dt, J = 7.3, 1.7Hz), 7.15 (1H, dt, J = 7.3, 1.7 Hz), 7.23 (1H, dd, J = 7.6, 1.7Hz), 7.30 (1H, dd, J = 7.6, 1.7Hz), 7.62 (1H, d, J = 1.5Hz), 7.78 (1H, dd, J = 8.3, 1.5Hz).
IR (KBr) νcm ^-1 : 1720, 1676, 1622, 1511, 1475, 1395, 1195, 750, 584
The free base (850 mg) obtained above was dissolved in ethyl acetate (2 ml), and 4N hydrochloric acid (ethyl acetate solution) (0.5 ml) was added at room temperature. The mixture was stirred at room temperature for 30 minutes and concentrated. Ethyl acetate (2 ml) was added to the residue, and the precipitated crystals were collected by filtration to give the title compound (900 mg) as a slightly yellow amorphous powder.

8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one p-toluene Sulfonate 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline- obtained in Example 39 2 (1H) -one hydrochloride (205 mg, 0.5 mmol) was mixed with 1N aqueous sodium hydroxide solution (10 ml) and extracted with ethyl acetate (30 ml × 3 times). The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and then the solvent was distilled off. Ethanol (3 ml) was added to the resulting residue to make a solution. Subsequently, a solution of p-toluenesulfonic acid monohydrate (95 mg, 0.5 mmol) in ethanol (3 ml) was added, and after stirring, ethanol (about 5.5 ml) was distilled off under reduced pressure. The residue was left at room temperature, and the precipitated crystals were collected by filtration and washed successively with ethanol and diethyl ether. Further, the title compound was obtained as colorless crystals (258 mg) having a melting point of 172-173 ° C. (decomposition) by drying under reduced pressure.
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ · C ₇ H ₈ O ₃ S: C, 63.85; H, 6.05; N, 4.80.
Experimental value: C, 63.77; H, 5.99; N, 4.69.

8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one sulfate 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H) obtained in Example 39 The title compound was converted to colorless crystals (218 mg) having a melting point of 155-156 ° C. (decomposition) by performing the same operation as in Example 360 using hydrochloride (205 mg, 0.5 mmol) and sulfuric acid (49 mg, 0.5 mmol). Got as.
Elemental analysis _{C 24 H 27 ClN 2 O 2} · H 2 SO 4 Calculated: C, 56.63; H, 5.74 ; N, 5.50.
Experimental values: C, 56.42; H, 5.86; N, 5.23.

8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one hydrogen bromide Acid salt 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 obtained in Example 39 (1H) -one By using the same procedure as in Example 360 using hydrochloride (205 mg, 0.5 mmol) and 48% hydrobromic acid (84 mg, 0.5 mmol), the title compound was melted at a melting point of 201-203 ° C. Decomposition) as colorless crystals (220 mg).
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ .HBr: C, 58.61; H, 5.74; N, 5.70.
Experimental value: C, 58.54; H, 5.85; N, 5.53.

参考例２０９で得た5-(2,3-ジヒドロ-2,2-ジメチル-1-ベンゾフラン-5-イル)-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(550mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点132-133℃の無色結晶(350mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.42 (6H, s), 1.61-1.75 (4H, m), 2.93-3.16 (10H, m), 6.78 (1H, t, J = 8.3Hz), 7.30-7.46 (4H, m), 7.79 (1H, d, J = 8.3Hz), 7.83 (1H, s), 9.36 (2H, br).
IR (KBr) νcm^-1: 2946, 1668, 1603, 1440, 1266, 1090, 750. 5-{[2- (2-Chlorophenyl) ethyl] amino} -1- (2,3-dihydro-2,2-dimethyl-1-benzofuran-5-yl) pentan-1-one hydrochloride

Tert-Butyl 5- (2,3-dihydro-2,2-dimethyl-1-benzofuran-5-yl) -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate obtained in Reference Example 209 ( The title compound was obtained as colorless crystals (350 mg) having a melting point of 132-133 ° C. by the same procedure as in Example 1 using 550 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.42 (6H, s), 1.61-1.75 (4H, m), 2.93-3.16 (10H, m), 6.78 (1H, t, J = 8.3Hz), 7.30 -7.46 (4H, m), 7.79 (1H, d, J = 8.3Hz), 7.83 (1H, s), 9.36 (2H, br).
IR (KBr) νcm ^-1 : 2946, 1668, 1603, 1440, 1266, 1090, 750.

参考例２１０で得た5-(3,4-ジヒドロ-2H-クロメン-6-イル)-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(750mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点154-155℃の無色結晶(586mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.72 (4H, m), 1.91 (2H, br.s), 2.77 (2H, br.s) 2.95-2.98 (4H, m), 3.08-3.15 (4H, m), 4.18 (2H, br.s), 6.79 (1H, d, J = 8.3Hz), 7.26-7.44 (4H, m), 7.69 (1H, d, J = 8.3Hz), 7.72 (1H, s), 9.19 (2H, br.s).
IR (KBr) νcm^-1: 2958, 1673, 1605, 1499, 1476, 1257, 1138, 1019, 758. 5-{[2- (2-Chlorophenyl) ethyl] amino} -1- (3,4-dihydro-2H-chromen-6-yl) -1-pentanone hydrochloride

Using tert-butyl 5- (3,4-dihydro-2H-chromen-6-yl) -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate (750 mg) obtained in Reference Example 210, The title compound was obtained as colorless crystals (586 mg) having a melting point of 154-155 ° C. by carrying out the same operation as in Example 1.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.72 (4H, m), 1.91 (2H, br.s), 2.77 (2H, br.s) 2.95-2.98 (4H, m), 3.08-3.15 (4H, m), 4.18 (2H, br.s), 6.79 (1H, d, J = 8.3Hz), 7.26-7.44 (4H, m), 7.69 (1H, d, J = 8.3Hz), 7.72 ( 1H, s), 9.19 (2H, br.s).
IR (KBr) νcm ^-1 : 2958, 1673, 1605, 1499, 1476, 1257, 1138, 1019, 758.

参考例２１１で得た5-{7-[(メチルアミノ)スルホニル]-2,3-ジヒドロ-1-ベンゾフラン-5-イル}-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(850mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点167-168℃の無色結晶(673mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.76 (4H, m), 2.45 (3H, d, J = 4.8Hz), 2.94-3.05 (8H, m), 3.31 (2H, t, J = 8.8Hz), 3.79 (3H, s), 4.80 (2H, t, J = 8.8Hz), 6.89 (1H, t, J = 7.6Hz), 6.98 (1H, d, J = 8.0Hz), 7.17(1H, d, J = 7.6Hz), 7.24 (1H, t, J = 8.0Hz), 7.47(1H, br.s), 8.05 (1H, s), 8.09 (1H, s), 9.19 (2H, br).
IR (KBr) νcm^-1: 3319, 2783, 2453, 1686, 1605, 1496, 1467, 1334, 1255, 1157, 1119, 758, 586. N-methyl-5- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- {7-[(Methylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamine obtained in Reference Example 211 The title compound was obtained as colorless crystals (673 mg) having a melting point of 167-168 ° C. by carrying out the same operation as in Example 1 using tert-butyl acid (850 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.76 (4H, m), 2.45 (3H, d, J = 4.8Hz), 2.94-3.05 (8H, m), 3.31 (2H, t, J = 8.8Hz), 3.79 (3H, s), 4.80 (2H, t, J = 8.8Hz), 6.89 (1H, t, J = 7.6Hz), 6.98 (1H, d, J = 8.0Hz), 7.17 (1H , d, J = 7.6Hz), 7.24 (1H, t, J = 8.0Hz), 7.47 (1H, br.s), 8.05 (1H, s), 8.09 (1H, s), 9.19 (2H, br) .
IR (KBr) νcm ^-1 : 3319, 2783, 2453, 1686, 1605, 1496, 1467, 1334, 1255, 1157, 1119, 758, 586.

参考例２１２で得た5-{7-[(メチルアミノ)スルホニル]-2,3-ジヒドロ-1-ベンゾフラン-5-イル}-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(500mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点182-183℃の無色結晶(430mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.76 (4H, m), 2.45 (3H, d, J = 4.8Hz), 2.97-3.11 (8H, m), 3.31 (2H, t, J = 8.8Hz), 4.80 (2H, t, J = 8.8Hz), 7.28-7.34 (2H, m), 7.39-7.41 (1H, m), 7.44-7.47 (2H, m), 8.05 (1H, s), 8.09 (1H, s), 9.28 (2H, br).
IR (KBr) νcm^-1: 3155, 2808, 1677, 1613, 1480, 1431, 1326, 1228, 1150, 766, 588. N-methyl-5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- {7-[(Methylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamic acid obtained in Reference Example 212 The same operation as in Example 1 was carried out using tert-butyl (500 mg) to give the title compound as colorless crystals (430 mg) having a melting point of 182-183 ° C.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.76 (4H, m), 2.45 (3H, d, J = 4.8Hz), 2.97-3.11 (8H, m), 3.31 (2H, t, J = 8.8Hz), 4.80 (2H, t, J = 8.8Hz), 7.28-7.34 (2H, m), 7.39-7.41 (1H, m), 7.44-7.47 (2H, m), 8.05 (1H, s), 8.09 (1H, s), 9.28 (2H, br).
IR (KBr) νcm ^-1 : 3155, 2808, 1677, 1613, 1480, 1431, 1326, 1228, 1150, 766, 588.

参考例２１３で得た5-{7-[(ジメチルアミノ)スルホニル]-2,3-ジヒドロ-1-ベンゾフラン-5-イル}-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(860mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点164-165℃の無色結晶(636mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.75 (4H, m), 2.70 (6H, s), 2.93-3.06 (8H, m), 3.31 (2H, t, J = 8.8Hz), 3.79 (3H, s), 4.79 (2H, t, J = 8.8Hz), 6.89 (1H, t, J = 7.6Hz), 6.98 (1H, d, J = 8.0Hz), 7.17 (1H, d, J = 7.6Hz), 7.23 (1H, t, J = 8.0Hz), 8.00 (1H, s), 8.13(1H, s), 9.17 (2H, br).
IR (KBr) νcm^-1: 2783, 1684, 1604, 1496, 1463, 1424, 1338, 1250, 1152, 1126, 956, 766, 585. N, N-dimethyl-5- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- {7-[(Dimethylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamine obtained in Reference Example 213 The title compound was obtained as colorless crystals (636 mg) having a melting point of 164-165 ° C. by performing the same operation as in Example 1 using tert-butyl acid (860 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.75 (4H, m), 2.70 (6H, s), 2.93-3.06 (8H, m), 3.31 (2H, t, J = 8.8Hz), 3.79 (3H, s), 4.79 (2H, t, J = 8.8Hz), 6.89 (1H, t, J = 7.6Hz), 6.98 (1H, d, J = 8.0Hz), 7.17 (1H, d, J = 7.6Hz), 7.23 (1H, t, J = 8.0Hz), 8.00 (1H, s), 8.13 (1H, s), 9.17 (2H, br).
IR (KBr) νcm ^-1 : 2783, 1684, 1604, 1496, 1463, 1424, 1338, 1250, 1152, 1126, 956, 766, 585.

参考例２１４で得た2-(2-クロロフェニル)エチル(5-{7-[(ジメチルアミノ)スルホニル]-2,3-ジヒドロ-1-ベンゾフラン-5-イル}-5-オキソペンチル)カルバミン酸 tert-ブチル(500mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点176-177℃の無色結晶(417mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.75 (4H, m), 2.70 (6H, s), 2.97-3.14 (8H, m), 3.32 (2H, t, J = 8.8Hz), 4.79 (2H, t, J = 8.8Hz), 7.29-7.33 (2H, m), 7.40 (1H, dd, J = 7.0, 1.7Hz), 7.45 (1H, dd, J = 7.0, 1.7Hz), 8.00 (1H, s), 8.13 (1H, s), 9.21 (2H, br).
IR (KBr) νcm^-1: 2776, 1684, 1601, 1461, 1424, 1334, 1265, 1151, 1121, 963, 758, 758, 584. N-dimethyl-5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

2- (2-Chlorophenyl) ethyl (5- {7-[(dimethylamino) sulfonyl] -2,3-dihydro-1-benzofuran-5-yl} -5-oxopentyl) carbamic acid obtained in Reference Example 214 The same operation as in Example 1 was carried out using tert-butyl (500 mg) to give the title compound as colorless crystals (417 mg) having a melting point of 176-177 ° C.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.75 (4H, m), 2.70 (6H, s), 2.97-3.14 (8H, m), 3.32 (2H, t, J = 8.8Hz), 4.79 (2H, t, J = 8.8Hz), 7.29-7.33 (2H, m), 7.40 (1H, dd, J = 7.0, 1.7Hz), 7.45 (1H, dd, J = 7.0, 1.7Hz), 8.00 ( 1H, s), 8.13 (1H, s), 9.21 (2H, br).
IR (KBr) νcm ^-1 : 2776, 1684, 1601, 1461, 1424, 1334, 1265, 1151, 1121, 963, 758, 758, 584.

参考例２１５で得た5-[8-(アミノスルホニル)-3,4-ジヒドロ-2H-クロメン-6-イル]-5-オキソペンチル[2-(2-メトキシフェニル)エチル]カルバミン酸 tert-ブチル(650mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点184-185℃の無色結晶(560mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.61-1.73 (4H, m), 1.95-1.98(2H, m), 2.86 (2H, t, J = 6.2Hz), 2.93-3.03 (8H, m), 3.78 (3H, s), 4.36 (2H, t, J = 5.1Hz), 6.89 (1H, t, J = 7.3Hz), 6.97 (1H, d, J = 8.0Hz), 7.16-7.25 (2H, m), 7.19 (2H, s), 7.96 (1H, d, J = 2.0Hz), 8.12 (1H, d, J = 2.0Hz), 9.23 (2H, br.s).
IR (KBr) νcm^-1: 3306, 3209, 2947, 1661, 1602, 1573, 1495, 1342, 1244, 1161, 1140, 766, 591. 6- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -8-chromansulfonamide hydrochloride

5- [8- (Aminosulfonyl) -3,4-dihydro-2H-chromen-6-yl] -5-oxopentyl [2- (2-methoxyphenyl) ethyl] carbamic acid tert- obtained in Reference Example 215 The title compound was obtained as colorless crystals (560 mg) with a melting point of 184-185 ° C. by carrying out the same operation as in Example 1 using butyl (650 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.61-1.73 (4H, m), 1.95-1.98 (2H, m), 2.86 (2H, t, J = 6.2Hz), 2.93-3.03 (8H, m) , 3.78 (3H, s), 4.36 (2H, t, J = 5.1Hz), 6.89 (1H, t, J = 7.3Hz), 6.97 (1H, d, J = 8.0Hz), 7.16-7.25 (2H, m), 7.19 (2H, s), 7.96 (1H, d, J = 2.0Hz), 8.12 (1H, d, J = 2.0Hz), 9.23 (2H, br.s).
IR (KBr) νcm ^-1 : 3306, 3209, 2947, 1661, 1602, 1573, 1495, 1342, 1244, 1161, 1140, 766, 591.

参考例２１６で得た5-[8-(アミノスルホニル)-3,4-ジヒドロ-2H-クロメン-6-イル]-5-オキソペンチル[2-(2-クロロフェニル)エチル]カルバミン酸 tert-ブチル(650mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点177-178℃の無色結晶(564mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.63-1.73 (4H, m), 1.95-1.99 (2H, m), 2.86 (2H, t, J=6.2Hz), 2.96 (2H, br.s), 3.02 (2H, t, J = 7.0Hz), 3.09-3.16 (4H, m), 4.36 (2H, t, J = 5.1Hz), 7.19(2H, s), 7.28-7.33 (2H, m), 7.40 (1H, dd, J = 7, 2.2Hz), 7.44 (1H, dd, J = 7, 2.2Hz), 7.96 (1H, d, J = 2.0Hz), 8.11 (1H, d, J = 2.0Hz), 9.36 (2H, s).
IR (KBr) νcm^-1: 3307, 3208, 1662, 1602, 1573, 1474, 1342, 1161, 1140, 1004, 907, 765, 591. 6- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -8-chromansulfonamide hydrochloride

Tert-Butyl 5- [8- (aminosulfonyl) -3,4-dihydro-2H-chromen-6-yl] -5-oxopentyl [2- (2-chlorophenyl) ethyl] carbamate obtained in Reference Example 216 (650 mg) was used in the same manner as in Example 1 to obtain the title compound as colorless crystals (564 mg) having a melting point of 177-178 ° C.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.63-1.73 (4H, m), 1.95-1.99 (2H, m), 2.86 (2H, t, J = 6.2Hz), 2.96 (2H, br.s) , 3.02 (2H, t, J = 7.0Hz), 3.09-3.16 (4H, m), 4.36 (2H, t, J = 5.1Hz), 7.19 (2H, s), 7.28-7.33 (2H, m), 7.40 (1H, dd, J = 7, 2.2Hz), 7.44 (1H, dd, J = 7, 2.2Hz), 7.96 (1H, d, J = 2.0Hz), 8.11 (1H, d, J = 2.0Hz ), 9.36 (2H, s).
IR (KBr) νcm ^-1 : 3307, 3208, 1662, 1602, 1573, 1474, 1342, 1161, 1140, 1004, 907, 765, 591.

参考例２０３で得た5-(5-クロロペンタノイル)-N-メチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(664mg) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(752mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(246mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.54-1.61 (2H, m), 1.71-1.78 (2H, m), 2.32 (3H, s), 2.46 (2H, t, J = 7.3Hz), 2.56-2.60 (2H, m), 2.65 (3H, s), 2.76-2.80 (2H, m), 2.96 (2H, t, J = 7.0Hz), 3.33 (2H, t, J = 8.8Hz), 3.82 (3H, s), 4.82-4.85 (1H, br), 4.86 (2H, t, J = 8.8Hz), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 8.04 (1H, d, J = 1.6Hz), 8.22 (1H, d, J = 1.6Hz).
IR (neat) νcm^-1: 3307, 1679, 1602, 1495, 1465, 1330, 1244, 1160, 1118, 756, 734, 587. 5- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -N-methyl-2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -N-methyl-2,3-dihydro-1-benzofuran-7-sulfonamide (664 mg) and N- [2- (2-methoxyphenyl) ethyl obtained in Reference Example 203 The title compound (246 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using -N-methylamine (752 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.61 (2H, m), 1.71-1.78 (2H, m), 2.32 (3H, s), 2.46 (2H, t, J = 7.3 Hz), 2.56-2.60 (2H, m), 2.65 (3H, s), 2.76-2.80 (2H, m), 2.96 (2H, t, J = 7.0Hz), 3.33 (2H, t, J = 8.8Hz), 3.82 (3H, s), 4.82-4.85 (1H, br), 4.86 (2H, t, J = 8.8Hz), 6.83-6.89 (2H, m), 7.12-7.19 (2H, m), 8.04 (1H, d , J = 1.6Hz), 8.22 (1H, d, J = 1.6Hz).
IR (neat) νcm ^-1 : 3307, 1679, 1602, 1495, 1465, 1330, 1244, 1160, 1118, 756, 734, 587.

参考例２０３で得た5-(5-クロロペンタノイル)-N-メチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(664mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(768mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(360mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.54-1.61 (2H, m), 1.71-1.78 (2H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.6Hz), 2.60-2.64 (2H, m), 2.66 (3H, d, J = 4.4Hz), 2.89-2.98 (4H, m), 3.34 (2H, t, J = 8.8Hz), 4.77 (1H, br.s), 4.87 (2H, t, J = 8.8Hz), 7.13 (1H, dt, J = 7.6, 1.5Hz), 7.18 (1H, dt, J = 7.6, 1.5Hz), 7.24 (1H, dd, J = 7.6, 1.5Hz), 7.32 (1H, dd, J = 7.6, 1.5Hz), 8.06 (1H, d, J = 1.5Hz), 8.23 (1H, d, J = 1.5Hz).
IR (neat) νcm^-1: 3307, 1680, 1603, 1475, 1329, 1263, 1159, 1119, 754, 585. 5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -N-methyl-2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -N-methyl-2,3-dihydro-1-benzofuran-7-sulfonamide (664 mg) and N- [2- (2-chlorophenyl) ethyl] obtained in Reference Example 203 The same operation as in Example 9 was carried out using -N-methylamine (768 mg) to give the title compound (360 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.54-1.61 (2H, m), 1.71-1.78 (2H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.6 Hz), 2.60-2.64 (2H, m), 2.66 (3H, d, J = 4.4Hz), 2.89-2.98 (4H, m), 3.34 (2H, t, J = 8.8Hz), 4.77 (1H, br.s) , 4.87 (2H, t, J = 8.8Hz), 7.13 (1H, dt, J = 7.6, 1.5Hz), 7.18 (1H, dt, J = 7.6, 1.5Hz), 7.24 (1H, dd, J = 7.6 , 1.5Hz), 7.32 (1H, dd, J = 7.6, 1.5Hz), 8.06 (1H, d, J = 1.5Hz), 8.23 (1H, d, J = 1.5Hz).
IR (neat) νcm ^-1 : 3307, 1680, 1603, 1475, 1329, 1263, 1159, 1119, 754, 585.

参考例２０４で得た5-(5-クロロペンタノイル)-N,N-ジメチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(692mg) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(752mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(466mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.56-1.63 (2H, m), 1.71-1.79 (2H, m), 2.34 (3H, s), 2.49 (2H, t, J = 7.6Hz), 2.58-2.62 (2H, m), 2.78-2.82 (2H, m), 2.84 (6H, s), 2.95 (2H, t, J = 7.3Hz), 3.32 (2H, t, J = 7.3Hz), 3.82 (3H, s), 4.82 (2H, t, J = 8.8Hz), 6.83-6.89 (2H, m), 7.13-7.19 (2H, m), 8.02 (1H, d, J = 1.7Hz), 8.19 (1H, d, J = 1.7Hz).
IR (neat) νcm^-1: 3307, 1680, 1603, 1475, 1329, 1263, 1159, 1119, 754, 585. 5- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -N, N-dimethyl-2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -N, N-dimethyl-2,3-dihydro-1-benzofuran-7-sulfonamide (692 mg) and N- [2- (2-methoxyphenyl) obtained in Reference Example 204 ) Ethyl] -N-methylamine (752 mg) was used in the same manner as in Example 9 to obtain the title compound (466 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.56-1.63 (2H, m), 1.71-1.79 (2H, m), 2.34 (3H, s), 2.49 (2H, t, J = 7.6 Hz), 2.58-2.62 (2H, m), 2.78-2.82 (2H, m), 2.84 (6H, s), 2.95 (2H, t, J = 7.3Hz), 3.32 (2H, t, J = 7.3Hz), 3.82 (3H, s), 4.82 (2H, t, J = 8.8Hz), 6.83-6.89 (2H, m), 7.13-7.19 (2H, m), 8.02 (1H, d, J = 1.7Hz), 8.19 ( (1H, d, J = 1.7Hz).
IR (neat) νcm ^-1 : 3307, 1680, 1603, 1475, 1329, 1263, 1159, 1119, 754, 585.

参考例２０４で得た5-(5-クロロペンタノイル)-N,N-ジメチル-2,3-ジヒドロ-1-ベンゾフラン-7-スルホンアミド(692mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(768mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(370mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.53-1.61 (2H, m), 1.70-1.78 (2H, m), 2.33 (3H, s), 2.47 (2H, t, J = 7.6Hz), 2.59-2.63 (2H, m), 2.84 (6H, s), 2.87-2.96 (4H, m), 3.32 (2H, t, J = 8.8Hz), 4.82 (2H, t, J = 8.8Hz), 7.12 (1H, dt, J = 7.6, 1.5Hz), 7.17 (1H, dt, J = 7.6, 1.5Hz), 7.24 (1H, dd, J = 7.6, 1.5Hz), 7.32 (1H, dd, J = 7.6, 1.5Hz), 8.02 (1H, d, J = 1.5Hz), 8.18 (1H, d, J = 1.5Hz).
IR (neat) νcm^-1: 1681, 1603, 1464, 1423, 1342, 1262, 1154, 1119, 958, 754, 583. 5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -N, N-dimethyl-2,3-dihydro-1-benzofuran-7-sulfonamide hydrochloride

5- (5-Chloropentanoyl) -N, N-dimethyl-2,3-dihydro-1-benzofuran-7-sulfonamide (692 mg) and N- [2- (2-chlorophenyl) obtained in Reference Example 204 The title compound (370 mg) was obtained as a pale yellow amorphous powder by conducting the same operation as in Example 9 using ethyl] -N-methylamine (768 mg).
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.53-1.61 (2H, m), 1.70-1.78 (2H, m), 2.33 (3H, s), 2.47 (2H, t, J = 7.6 Hz), 2.59-2.63 (2H, m), 2.84 (6H, s), 2.87-2.96 (4H, m), 3.32 (2H, t, J = 8.8Hz), 4.82 (2H, t, J = 8.8Hz), 7.12 (1H, dt, J = 7.6, 1.5Hz), 7.17 (1H, dt, J = 7.6, 1.5Hz), 7.24 (1H, dd, J = 7.6, 1.5Hz), 7.32 (1H, dd, J = 7.6 , 1.5Hz), 8.02 (1H, d, J = 1.5Hz), 8.18 (1H, d, J = 1.5Hz).
IR (neat) νcm ^-1 : 1681, 1603, 1464, 1423, 1342, 1262, 1154, 1119, 958, 754, 583.

参考例２０８で得た6-(5-クロロペンタノイル)-8-クロマンスルホンアミド(664mg) およびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミン(752mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物を融点121-122℃の無色結晶(447mg)として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.51-1.59 (2H, m), 1.68-1.75 (2H, m), 2.09-2.15 (2H, m), 2.30 (3H, s), 2.42-2.46 (2H, m), 2.54-2.58 (2H, m), 2.74-2.78 (2H, m), 2.88-2.93 (4H, m), 3.82 (3H, s), 4.47 (2H, t, J = 5.3Hz), 5.17 (2H, br.s), 6.82-6.88 (2H, m), 7.11-7.19 (2H, m), 7.91 (1H, d, J = 1.7Hz), 8.28 (1H, d, J = 1.7Hz).
IR (neat) νcm^-1: 3388, 3283, 1684, 1600, 1461, 1324, 1243, 1165, 1144, 1032, 752. 6- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -8-chromansulfonamide hydrochloride

Using 6- (5-chloropentanoyl) -8-chromansulfonamide (664 mg) and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine (752 mg) obtained in Reference Example 208, The title compound was obtained as colorless crystals (447 mg) having a melting point of 121-122 ° C. by carrying out the same operation as in Example 9.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.51-1.59 (2H, m), 1.68-1.75 (2H, m), 2.09-2.15 (2H, m), 2.30 (3H, s), 2.42-2.46 (2H, m), 2.54-2.58 (2H, m), 2.74-2.78 (2H, m), 2.88-2.93 (4H, m), 3.82 (3H, s), 4.47 (2H, t, J = 5.3Hz ), 5.17 (2H, br.s), 6.82-6.88 (2H, m), 7.11-7.19 (2H, m), 7.91 (1H, d, J = 1.7Hz), 8.28 (1H, d, J = 1.7 Hz).
IR (neat) νcm ^-1 : 3388, 3283, 1684, 1600, 1461, 1324, 1243, 1165, 1144, 1032, 752.

参考例２０８で得た6-(5-クロロペンタノイル)-8-クロマンスルホンアミド(664mg) およびN-[2-(2-クロロフェニル)エチル]-N-メチルアミン(768mg) を用いて、実施例９と同様の操作を行うことにより、表題化合物(360mg) を淡黄色非晶状粉末として得た。
¹H NMR (フリー塩基; 400MHz, CDCl₃) δ 1.51-1.59 (2H, m), 1.68-1.75 (2H, m), 2.09-2.15 (2H, m), 2.32 (3H, s), 2.46 (2H, t, J = 7.3Hz), 2.58-2.62 (2H, m), 2.87-2.93 (6H, m), 4.48 (2H, t, J = 5.3Hz), 5.31 (2H, br.s), 7.12 (1H, dt, J = 7.3, 2Hz), 7.17 (1H, dt, J = 7.3, 2Hz), 7.22 (1H, dd, J = 7.3, 1.7Hz), 7.32 (1H, dd, J = 7.3, 1.7Hz), 7.90 (1H, d, J = 1.7Hz), 8.27 (1H, d, J = 1.7Hz).
IR (neat) νcm^-1: 3384, 3276, 1684, 1599, 1477, 1324, 1161, 1144, 901, 757. 6- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -8-chromansulfonamide hydrochloride

Using 6- (5-chloropentanoyl) -8-chromansulfonamide (664 mg) and N- [2- (2-chlorophenyl) ethyl] -N-methylamine (768 mg) obtained in Reference Example 208 The same operation as in Example 9 was performed to give the title compound (360 mg) as a pale yellow amorphous powder.
¹ H NMR (free base; 400 MHz, CDCl ₃ ) δ 1.51-1.59 (2H, m), 1.68-1.75 (2H, m), 2.09-2.15 (2H, m), 2.32 (3H, s), 2.46 (2H , t, J = 7.3Hz), 2.58-2.62 (2H, m), 2.87-2.93 (6H, m), 4.48 (2H, t, J = 5.3Hz), 5.31 (2H, br.s), 7.12 ( 1H, dt, J = 7.3, 2Hz), 7.17 (1H, dt, J = 7.3, 2Hz), 7.22 (1H, dd, J = 7.3, 1.7Hz), 7.32 (1H, dd, J = 7.3, 1.7Hz ), 7.90 (1H, d, J = 1.7Hz), 8.27 (1H, d, J = 1.7Hz).
IR (neat) νcm ^-1 : 3384, 3276, 1684, 1599, 1477, 1324, 1161, 1144, 901, 757.

8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one citrate 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H obtained in Example 39 ) -One Hydrochloride (205 mg, 0.5 mmol) and citric acid (96 mg, 0.5 mmol) were used in the same manner as in Example 360 to give the title compound as colorless crystals (melting point: 100-102 ° C. (decomposition)). 278 mg).
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ · C ₆ H ₈ O ₇ : C, 59.75; H, 5.85; N, 4.65.
Experimental value: C, 59.34; H, 6.21; N, 4.39.

8- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one succinate 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H obtained in Example 39 ) -One Hydrochloride (205 mg, 0.5 mmol) and succinic acid (59 mg, 0.5 mmol) were used in the same manner as in Example 360 to give the title compound as colorless crystals (melting point: 138-140 ° C. (decomposition)). 217 mg).
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ · C ₄ H ₆ O ₄ : C, 63.57; H, 6.29; N, 5.30.
Experimental value: C, 63.37; H, 6.20; N, 5.10.

8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one methanesulfonic acid Salt 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (obtained in Example 39 1H) -one Hydrochloride (205 mg, 0.5 mmol) and methanesulfonic acid (48 mg, 0.5 mmol) were used in the same manner as in Example 360 to give the title compound as a colorless compound having a melting point of 186-188 ° C. (decomposition). Obtained as crystals (213 mg).
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ .CH ₄ O ₃ S: C, 59.22; H, 6.16; N, 5.52.
Experimental value: C, 59.07; H, 6.25; N, 5.35.

8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one L (+ ) -Tartrate 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline obtained in Example 39 -2 (1H) -one Hydrochloride (205 mg, 0.5 mmol) and L (+)-tartaric acid (75 mg, 0.5 mmol) were used in the same manner as in Example 360 to obtain the title compound with a melting point of 103-105 Obtained as colorless crystals (225 mg) at ℃ (decomposition).

8- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one oxalate 8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinoline-2 (1H obtained in Example 39 ) -One Hydrochloride (205 mg, 0.5 mmol) and oxalic acid (45 mg, 0.5 mmol) were used in the same manner as in Example 360 to give the title compound as colorless crystals (melting point: 161-163 ° C. (decomposition)). 221 mg).
Elemental analysis Calculated as C ₂₄ H ₂₇ ClN ₂ O ₂ · C ₂ H ₂ O ₄ : C, 62.33; H, 5.83; N, 5.59.
Experimental value: C, 62.15; H, 6.00; N, 5.44.

5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one p-toluenesulfonate Example 143 5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (458 mg, 1.05) mmol) and p-toluenesulfonic acid (200 mg, 1.05 mmol) were used in the same manner as in Example 360 to obtain the title compound as colorless crystals (566 mg) having a melting point of 148-150 ° C.
^{1 H NMR (200MHz, DMSO-} d 6) δ 1.69 (4H, br), 2.28 (3H, s), 3.09 (8H, m), 3.38 (3H, s), 3.39 (3H, s), 7.10 (2H , d, J = 8.0 Hz), 7.25-7.51 (7H, m), 7.73 (1H, s), 7.81 (1H, d, J = 7.6 Hz), 8.52 (2H, br).
Elemental analysis Calculated as C ₂₂ H ₂₆ ClN ₃ O ₂ · C ₇ H ₈ O ₃ S: C, 60.88; H, 5.99; N, 7.34.
Experimental value: C, 60.95; H, 6.00; N, 7.47.

参考例２１８で得た2-(2-クロロフェニル)エチル[5-(1-メチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(500mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点192-193℃の無色結晶(340mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.67-1.73 (4H, m), 2.97 (2H, br.s), 3.04 (2H, t, J = 6.7Hz), 3.11 (4H, br.s), 3.31 (3H, s), 7.18 (1H, d, J = 8.3Hz), 7.27-7.34 (2H, m), 7.39 (1H, dd, J = 7.0, 2.0Hz), 7.44 (1H, dd, J = 7.0, 2.0Hz), 7.52 (1H, d, J = 1.7Hz), 7.76 (1H, dd, J = 8.3, 1.7Hz), 9.20 (2H, br.s), 11.19 (1H, s).
IR (KBr) νcm^-1: 3432, 2776, 1749, 1666, 1630, 1487, 1319, 1272, 808, 750. 5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

2- (2-Chlorophenyl) ethyl [5- (1-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamic acid tert obtained in Reference Example 218 The title compound was obtained as colorless crystals (340 mg) having a melting point of 192-193 ° C. by carrying out the same operation as in Example 1 using -butyl (500 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.67-1.73 (4H, m), 2.97 (2H, br.s), 3.04 (2H, t, J = 6.7Hz), 3.11 (4H, br.s) , 3.31 (3H, s), 7.18 (1H, d, J = 8.3Hz), 7.27-7.34 (2H, m), 7.39 (1H, dd, J = 7.0, 2.0Hz), 7.44 (1H, dd, J = 7.0, 2.0Hz), 7.52 (1H, d, J = 1.7Hz), 7.76 (1H, dd, J = 8.3, 1.7Hz), 9.20 (2H, br.s), 11.19 (1H, s).
IR (KBr) νcm ^-1 : 3432, 2776, 1749, 1666, 1630, 1487, 1319, 1272, 808, 750.

参考例２１８で得た2-(2-クロロフェニル)エチル[5-(3-メチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(500mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点127-129℃の無色結晶(354mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.68-1.74 (4H, m), 2.98(2H, br.s), 3.07 (2H, t, J = 6.8Hz), 3.11 (4H, br.s), 3.33 (3H, s), 7.06 (1H, d, J = 8.3Hz), 7.27-7.34 (2H, m), 7.39 (1H, dd, J = 7.0, 2.0Hz), 7.44 (1H, dd, J = 7.0, 2.0Hz), 7.67 (1H, d, J = 1.7Hz), 7.72 (1H, dd, J = 8.3, 1.7Hz), 9.24 (2H, br.s), 11.32 (1H, s).
IR (KBr) νcm^-1: 3356, 2733, 1703, 1677, 1623, 1474, 1370, 1252, 1181, 757, 691. 6- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

2- (2-Chlorophenyl) ethyl [5- (3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxopentyl] carbamic acid tert obtained in Reference Example 218 The title compound was obtained as colorless crystals (354 mg) having a melting point of 127-129 ° C. by conducting the same operation as in Example 1 using -butyl (500 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.68-1.74 (4H, m), 2.98 (2H, br.s), 3.07 (2H, t, J = 6.8Hz), 3.11 (4H, br.s) , 3.33 (3H, s), 7.06 (1H, d, J = 8.3Hz), 7.27-7.34 (2H, m), 7.39 (1H, dd, J = 7.0, 2.0Hz), 7.44 (1H, dd, J = 7.0, 2.0Hz), 7.67 (1H, d, J = 1.7Hz), 7.72 (1H, dd, J = 8.3, 1.7Hz), 9.24 (2H, br.s), 11.32 (1H, s).
IR (KBr) νcm ^-1 : 3356, 2733, 1703, 1677, 1623, 1474, 1370, 1252, 1181, 757, 691.

参考例２１９で得た2-(2-クロロ-4-ヒドロキシフェニル)エチル[5-(1-メチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(400mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点202-204℃の無色結晶(330mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.66-1.68 (4H, m), 2.95-3.06 (8H, m), 3.31 (3H, s), 6.78 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.3Hz), 7.18 (1H, d, J = 8.3Hz), 7.52 (1H, d, J = 1.5Hz), 7.76 (1H, dd, J = 8.3, 1.5Hz), 8.96 (2H, br.s), 9.92 (1H, s), 11.16 (1H, s).
IR (KBr) νcm^-1: 3206, 1703, 1665, 1622, 1502, 1438, 1310, 1083, 705. 5- (5-{[2- (2-Chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

2- (2-Chloro-4-hydroxyphenyl) ethyl [5- (1-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxo obtained in Reference Example 219 The title compound was obtained as colorless crystals (330 mg) having a melting point of 202-204 ° C. by performing the same procedure as in Example 1 using tert-butyl pentyl] carbamate (400 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.66-1.68 (4H, m), 2.95-3.06 (8H, m), 3.31 (3H, s), 6.78 (1H, dd, J = 8.3, 2.4Hz) , 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.3Hz), 7.18 (1H, d, J = 8.3Hz), 7.52 (1H, d, J = 1.5Hz), 7.76 (1H, dd, J = 8.3, 1.5Hz), 8.96 (2H, br.s), 9.92 (1H, s), 11.16 (1H, s).
IR (KBr) νcm ^-1 : 3206, 1703, 1665, 1622, 1502, 1438, 1310, 1083, 705.

参考例２１９で得た2-(2-クロロ-4-ヒドロキシフェニル)エチル[5-(3-メチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(250mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点201-203℃の無色結晶(202mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.67-1.68 (4H, m), 2.97-3.08 (8H, m), 3.33 (3H, s), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.06 (1H, d, J = 8.1Hz), 7.16 (1H, d, J = 8.3Hz), 7.67 (1H, d, J = 1.7Hz), 7.72 (1H, dd, J = 8.1, 1.7Hz), 8.97 (2H, br.s), 9.92 (1H, s), 11.30 (1H, s).
IR (KBr) νcm^-1: 3120, 2946, 2797, 1695, 1673, 1612, 1502, 1469, 1180, 691. 6- (5-{[2- (2-Chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

2- (2-Chloro-4-hydroxyphenyl) ethyl [5- (3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-oxo obtained in Reference Example 219 The title compound was obtained as colorless crystals (202 mg) having a melting point of 201-203 ° C. by performing the same procedure as in Example 1 using tert-butyl pentyl] carbamate (250 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.67-1.68 (4H, m), 2.97-3.08 (8H, m), 3.33 (3H, s), 6.73 (1H, dd, J = 8.3, 2.4Hz) , 6.85 (1H, d, J = 2.4Hz), 7.06 (1H, d, J = 8.1Hz), 7.16 (1H, d, J = 8.3Hz), 7.67 (1H, d, J = 1.7Hz), 7.72 (1H, dd, J = 8.1, 1.7Hz), 8.97 (2H, br.s), 9.92 (1H, s), 11.30 (1H, s).
IR (KBr) νcm ^-1 : 3120, 2946, 2797, 1695, 1673, 1612, 1502, 1469, 1180, 691.

参考例２２０で得た2-(2-クロロ-4-ヒドロキシフェニル)エチル[5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(260mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点195-197℃の無色結晶(212mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.67-1.70 (4H, m), 2.97-3.00 (6H, m), 3.09 (2H, t, J = 6.6Hz), 3.36 (3H, s), 3.38 (3H, s), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.3Hz), 7.25 (1H, d, J = 8.3Hz), 7.72 (1H, d, J = 1.7Hz), 7.80 (1H, dd, J = 8.3, 1.7Hz), 8.99 (2H, br.s), 9.92 (1H, s).
IR (KBr) νcm^-1: 3091, 2951, 2780, 1707, 1675, 1622, 1501, 1461, 1251, 1190. 5- (5-{[2- (2-Chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

2- (2-Chloro-4-hydroxyphenyl) ethyl [5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5 obtained in Reference Example 220 The title compound was obtained as colorless crystals (212 mg) with a melting point of 195-197 ° C. by the same procedure as in Example 1 using tert-butyl carbamate (260 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.67-1.70 (4H, m), 2.97-3.00 (6H, m), 3.09 (2H, t, J = 6.6Hz), 3.36 (3H, s), 3.38 (3H, s), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.3Hz), 7.25 (1H, d, J = 8.3Hz), 7.72 (1H, d, J = 1.7Hz), 7.80 (1H, dd, J = 8.3, 1.7Hz), 8.99 (2H, br.s), 9.92 (1H, s).
IR (KBr) νcm ^-1 : 3091, 2951, 2780, 1707, 1675, 1622, 1501, 1461, 1251, 1190.

参考例２２２で得た5-クロロ-1-(1-メチル-2,2-ジオキシド-5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン-8-イル)-1-ペンタノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を 非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.53-1.78 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.63 (2H, m), 2.79-2.96 (6H, m), 3.31 (3H, s), 3.76 (2H, t, J = 5.4 Hz), 7.11-7.34 (5H, m), 7.44 (1H, s). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinolin-8-yl) -1-pentanone hydrochloride

5-Chloro-1- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] obtained in Reference Example 222 By performing the same operation as in Example 9 using quinolin-8-yl) -1-pentanone and N- [2- (2-chlorophenyl) ethyl] -N-methylamine, the title compound was converted to an amorphous powder. Got as.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.53-1.78 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.63 (2H, m), 2.79-2.96 (6H, m), 3.31 (3H, s), 3.76 (2H, t, J = 5.4 Hz), 7.11-7.34 (5H, m), 7.44 (1H , s).

参考例２２２で得た5-クロロ-1-(1-メチル-2,2-ジオキシド-5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン-8-イル)-1-ペンタノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.57-1.79 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.34 (3H, s), 2.49 (2H, t, J = 7.0 Hz), 2.60 (2H, m), 2.72-2.85 (4H, m), 2.94 (2H, t, J = 7.0 Hz), 3.31 (3H, s), 3.76 (2H, t, J = 5.4 Hz), 3.81 (3H, s), 6.82-6.91 (2H, m), 7.12-7.28 (3H, m), 7.44 (1H, s). 5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] -1- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] Thiadiazolo [4,3,2-ij] quinolin-8-yl) -1-pentanone hydrochloride

5-Chloro-1- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] obtained in Reference Example 222 By performing the same operation as in Example 9 using quinolin-8-yl) -1-pentanone and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine, the title compound was amorphous. Obtained as a powder.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.57-1.79 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.34 (3H, s), 2.49 (2H, t, J = 7.0 Hz), 2.60 (2H, m), 2.72-2.85 (4H, m), 2.94 (2H, t, J = 7.0 Hz), 3.31 (3H, s), 3.76 (2H, t, J = 5.4 Hz), 3.81 (3H, s), 6.82-6.91 (2H, m), 7.12-7.28 (3H, m), 7.44 (1H, s).

参考例２２３で得た2-(2-クロロフェニル)エチル[5-(1-メチル-2,2-ジオキシド-5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン-8-イル)-5-オキソペンチル]カルバミン酸tert-ブチルを用い、参考例１と同様の操作を行うことにより、表題化合物を融点154-155℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.53-1.78 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.48 (2H, t, J = 7.4 Hz), 2.63 (2H, m), 2.79-2.96 (6H, m), 3.31 (3H, s), 3.75 (2H, t, J = 5.4 Hz), 4.61 (1H, br), 7.15-7.34 (5H, m), 7.44 (1H, s). 5-{[2- (2-chlorophenyl) ethyl] amino} -1- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4, 3,2-ij] quinolin-8-yl) -1-pentanone hydrochloride

2- (2-Chlorophenyl) ethyl [5- (1-methyl-2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3] obtained in Reference Example 223 , 2-ij] Quinolin-8-yl) -5-oxopentyl] carbamate tert-butyl was treated in the same manner as in Reference Example 1 to give the title compound as colorless crystals with a melting point of 154-155 ° C. It was.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.53-1.78 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.48 (2H, t, J = 7.4 Hz), 2.63 (2H, m), 2.79-2.96 (6H, m), 3.31 (3H, s), 3.75 (2H, t, J = 5.4 Hz), 4.61 (1H, br), 7.15-7.34 (5H, m), 7.44 (1H , s).

参考例２２４で得た5-クロロ-1-(2,2-ジオキシド-5,6-ジヒドロ-1H,4H-[1,2,5]チアジアゾロ[4,3,2-ij]キノリン-8-イル)-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用い、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点125℃（分解）の淡黄色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.51-1.79 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.48 (2H, t, J = 7.4 Hz), 2.63 (2H, m), 2.78-2.99 (6H, m), 3.75 (2H, t, J = 5.4 Hz), 4.61 (1H, br), 7.15-7.34 (5H, m), 7.45 (1H, s), 11.58 (1H, s). 5-{[2- (2-chlorophenyl) ethyl] amino} -1- (2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2- ij] quinolin-8-yl) -1-pentanone hydrochloride

5-chloro-1- (2,2-dioxide-5,6-dihydro-1H, 4H- [1,2,5] thiadiazolo [4,3,2-ij] quinoline-8- obtained in Reference Example 224 Yl) -1-pentanone and 2- (2-chlorophenyl) ethylamine were used in the same manner as in Reference Example 19 and Example 1 to obtain the title compound as pale yellow crystals having a melting point of 125 ° C. (decomposition). It was.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.51-1.79 (4H, m), 2.19 (2H, quintet, J = 6.0 Hz), 2.48 (2H, t, J = 7.4 Hz), 2.63 (2H, m), 2.78-2.99 (6H, m), 3.75 (2H, t, J = 5.4 Hz), 4.61 (1H, br), 7.15-7.34 (5H, m), 7.45 (1H, s), 11.58 (1H , s).

参考例２２６で得た5-クロロ-1-(2,2-ジオキシド-3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン-6-イル)-1-ペンタノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.55-1.89 (4H, m), 2.53 (3H, s), 2.67-2.79 (4H, m), 2.86 (2H, m), 2.98 (2H, m), 4.54 (2H, s), 5.69 (1H, br), 6.60 (1H, d, J = 8.0 Hz), 7.13-7.32 (4H, m), 7.47-7.55 (2H, m), 10.81 (1H, s). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl ) -1-Pentanone hydrochloride

5-chloro-1- (2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1-pentanone obtained in Reference Example 226 and N- [ The title compound was obtained as an amorphous powder by the same procedure as in Example 9 using 2- (2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.55-1.89 (4H, m), 2.53 (3H, s), 2.67-2.79 (4H, m), 2.86 (2H, m), 2.98 (2H, m ), 4.54 (2H, s), 5.69 (1H, br), 6.60 (1H, d, J = 8.0 Hz), 7.13-7.32 (4H, m), 7.47-7.55 (2H, m), 10.81 (1H, s).

参考例２２６で得た5-クロロ-1-(2,2-ジオキシド-3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン-6-イル)-1-ペンタノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.55-1.89 (4H, m), 2.60 (3H, s), 2.67-2.79 (4H, m), 2.86 (2H, m), 2.98 (2H, m), 3.76 (3H, s), 4.45 (2H, s), 5.69 (1H, br), 6.54 (1H, d, J = 8.0 Hz), 6.77-6.84 (2H, m), 7.09-7.18 (2H, m), 7.47-7.55 (2H, m), 10.81 (1H, s). 1- (2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -5-[[2- (2-methoxyphenyl) ethyl] (methyl) Amino] -1-pentanone hydrochloride

5-chloro-1- (2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1-pentanone obtained in Reference Example 226 and N- [ The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9 using 2- (2-methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.55-1.89 (4H, m), 2.60 (3H, s), 2.67-2.79 (4H, m), 2.86 (2H, m), 2.98 (2H, m ), 3.76 (3H, s), 4.45 (2H, s), 5.69 (1H, br), 6.54 (1H, d, J = 8.0 Hz), 6.77-6.84 (2H, m), 7.09-7.18 (2H, m), 7.47-7.55 (2H, m), 10.81 (1H, s).

参考例２２６で得た5-クロロ-1-(2,2-ジオキシド-3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン-6-イル)-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用い、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点197-199℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.89 (4H, m), 2.67-2.79 (4H, m), 2.86 (2H, m), 2.98 (2H, m), 4.54 (2H, s), 4.63 (1H, br), 5.68 (1H, br), 6.61 (1H, d, J = 8.0 Hz), 7.11-7.32 (4H, m), 7.43-7.49 (2H, m), 10.82 (1H, s). 5-{[2- (2-chlorophenyl) ethyl] amino} -1- (2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1 -Pentanone hydrochloride

5-chloro-1- (2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1-pentanone obtained in Reference Example 226 and 2- ( The title compound was obtained as colorless crystals having a melting point of 197-199 ° C. by sequentially performing the same operations as in Reference Example 19 and Example 1 using 2-chlorophenyl) ethylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.54-1.89 (4H, m), 2.67-2.79 (4H, m), 2.86 (2H, m), 2.98 (2H, m), 4.54 (2H, s ), 4.63 (1H, br), 5.68 (1H, br), 6.61 (1H, d, J = 8.0 Hz), 7.11-7.32 (4H, m), 7.43-7.49 (2H, m), 10.82 (1H, s).

参考例２２８で得た5-クロロ-1-(1,3-ジメチル-2,2-ジオキシド-3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン-6-イル)-1-ペンタノンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.53-1.79 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.77 (3H, s), 2.87-2.97 (4H, m), 3.39 (3H, s), 4.69 (2H, s), 6.92 (1H, d, J = 8.8 Hz), 7.11-7.34 (4H, m), 7.74 (1H, d, J = 1.8 Hz), 7.91 (1H, dd, J = 8.8, 2.2 Hz). 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (1,3-dimethyl-2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothi Asiadin-6-yl) -1-pentanone hydrochloride

5-Chloro-1- (1,3-dimethyl-2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1 obtained in Reference Example 228 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9 using -pentanone and N- [2- (2-chlorophenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.53-1.79 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.77 ( 3H, s), 2.87-2.97 (4H, m), 3.39 (3H, s), 4.69 (2H, s), 6.92 (1H, d, J = 8.8 Hz), 7.11-7.34 (4H, m), 7.74 (1H, d, J = 1.8 Hz), 7.91 (1H, dd, J = 8.8, 2.2 Hz).

参考例２２８で得た5-クロロ-1-(1,3-ジメチル-2,2-ジオキシド-3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン-6-イル)-1-ペンタノンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.55-1.80 (4H, m), 2.33 (3H, s), 2.48 (2H, t, J = 7.0 Hz), 2.58 (2H, m), 2.76 (3H, s), 2.80 (2H, m), 2.95 (2H, t, J = 6.6 Hz), 3.39 (3H, s), 3.81 (3H, s), 4.68 (2H, s), 6.82-6.94 (3H, m), 7.12-7.21 (2H, m), 7.74 (1H, d, J = 1.8 Hz), 7.92 (1H, dd, J = 8.4, 1.8 Hz). 1- (1,3-Dimethyl-2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -5-[[2- (2-methoxyphenyl ) Ethyl] (methyl) amino] -1-pentanone hydrochloride

5-Chloro-1- (1,3-dimethyl-2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1 obtained in Reference Example 228 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9 using -pentanone and N- [2- (2-methoxyphenyl) ethyl] -N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.55-1.80 (4H, m), 2.33 (3H, s), 2.48 (2H, t, J = 7.0 Hz), 2.58 (2H, m), 2.76 ( 3H, s), 2.80 (2H, m), 2.95 (2H, t, J = 6.6 Hz), 3.39 (3H, s), 3.81 (3H, s), 4.68 (2H, s), 6.82-6.94 (3H , m), 7.12-7.21 (2H, m), 7.74 (1H, d, J = 1.8 Hz), 7.92 (1H, dd, J = 8.4, 1.8 Hz).

参考例２２８で得た5-クロロ-1-(1,3-ジメチル-2,2-ジオキシド-3,4-ジヒドロ-1H-2,1,3-ベンゾチアジアジン-6-イル)-1-ペンタノンおよび2-(2-クロロフェニル)エチルアミンを用い、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点164-165℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.51-1.76 (4H, m), 2.48 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.77 (3H, s), 2.87-2.97 (4H, m), 3.39 (3H, s), 3.92 (1H, br), 4.69 (2H, s), 6.92 (1H, d, J = 8.8 Hz), 7.11-7.34 (4H, m), 7.74 (1H, s), 7.91 (1H, d, J = 8.8 Hz). 5-{[2- (2-chlorophenyl) ethyl] amino} -1- (1,3-dimethyl-2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazine- 6-yl) -1-pentanone hydrochloride

5-Chloro-1- (1,3-dimethyl-2,2-dioxide-3,4-dihydro-1H-2,1,3-benzothiadiazin-6-yl) -1 obtained in Reference Example 228 The title compound was obtained as colorless crystals having a melting point of 164-165 ° C. by sequentially performing the same operations as in Reference Example 19 and Example 1 using -pentanone and 2- (2-chlorophenyl) ethylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.51-1.76 (4H, m), 2.48 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.77 (3H, s), 2.87- 2.97 (4H, m), 3.39 (3H, s), 3.92 (1H, br), 4.69 (2H, s), 6.92 (1H, d, J = 8.8 Hz), 7.11-7.34 (4H, m), 7.74 (1H, s), 7.91 (1H, d, J = 8.8 Hz).

参考例２３１で得た5-(5-クロロペンタノイル)-2-メチル-1H-イソインドール-1,3(2H)-ジオンおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.55-1.89 (4H, m), 2.34 (3H, s), 2.49 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.86-2.97 (2H, m), 3.05 (2H, t, J = 7.0 Hz), 3.22 (3H, s), 7.10-7.33 (4H, m), 7.94 (1H, d, J = 7.8 Hz), 8.29 (1H, d, J = 8.4 Hz), 8.37 (1H, s). 5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2-methyl-1H-isoindole-1,3 (2H) -dione hydrochloride

5- (5-Chloropentanoyl) -2-methyl-1H-isoindole-1,3 (2H) -dione and N- [2- (2-chlorophenyl) ethyl] -N-methyl obtained in Reference Example 231 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9 using amine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.55-1.89 (4H, m), 2.34 (3H, s), 2.49 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.86- 2.97 (2H, m), 3.05 (2H, t, J = 7.0 Hz), 3.22 (3H, s), 7.10-7.33 (4H, m), 7.94 (1H, d, J = 7.8 Hz), 8.29 (1H , d, J = 8.4 Hz), 8.37 (1H, s).

参考例２３１で得た5-(5-クロロペンタノイル)-2-メチル-1H-イソインドール-1,3(2H)-ジオンおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.56-1.87 (4H, m), 2.33 (3H, s), 2.49 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.71-2.82 (2H, m), 3.05 (2H, t, J = 6.8 Hz), 3.21 (3H, s), 3.82 (3H, s), 6.85 (2H, t, J = 8.6 Hz), 7.13 (2H, d, J = 7.4 Hz), 7.93 (1H, d, J = 7.8 Hz), 8.30 (1H, d, J = 8.4 Hz), 8.37 (1H, s). 5- {5-[[2- (2-Methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -2-methyl-1H-isoindole-1,3 (2H) -dione hydrochloride

5- (5-Chloropentanoyl) -2-methyl-1H-isoindole-1,3 (2H) -dione and N- [2- (2-methoxyphenyl) ethyl] -N- obtained in Reference Example 231 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9 using methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.56-1.87 (4H, m), 2.33 (3H, s), 2.49 (2H, t, J = 7.0 Hz), 2.61 (2H, m), 2.71- 2.82 (2H, m), 3.05 (2H, t, J = 6.8 Hz), 3.21 (3H, s), 3.82 (3H, s), 6.85 (2H, t, J = 8.6 Hz), 7.13 (2H, d , J = 7.4 Hz), 7.93 (1H, d, J = 7.8 Hz), 8.30 (1H, d, J = 8.4 Hz), 8.37 (1H, s).

参考例２３２で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]アセトアミドおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ1.53-1.78 (4H, m), 1.94 (3H, s), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.78-2.98 (6H, m), 3.31 (2H, dd, J = 16.4, 6.8 Hz), 4.74 (1H, m), 5.96 (1H, d, J = 7.2 Hz), 7.09-7.34 (5H, m), 7.78 (2H, m). N- (5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) acetamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide and N- [2- (2-chlorophenyl) ethyl] -N— obtained in Reference Example 232 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9 using methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ1.53-1.78 (4H, m), 1.94 (3H, s), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.78-2.98 (6H, m), 3.31 (2H, dd, J = 16.4, 6.8 Hz), 4.74 (1H, m), 5.96 (1H, d, J = 7.2 Hz), 7.09- 7.34 (5H, m), 7.78 (2H, m).

参考例２３２で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]アセトアミドおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用い、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.56-1.78 (4H, m), 1.94 (3H, s), 2.33 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.78-2.98 (6H, m), 3.31 (2H, dd, J = 16.4, 6.8 Hz), 3.81 (3H, s), 4.74 (1H, m), 6.04 (1H, d, J = 7.2 Hz), 6.81-6.90 (2H, m), 7.11-7.30 (3H, m), 7.78 (2H, m). N- (5- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) acetamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide and N- [2- (2-methoxyphenyl) ethyl] -N obtained in Reference Example 232 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9 using methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.56-1.78 (4H, m), 1.94 (3H, s), 2.33 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.60 ( 2H, m), 2.78-2.98 (6H, m), 3.31 (2H, dd, J = 16.4, 6.8 Hz), 3.81 (3H, s), 4.74 (1H, m), 6.04 (1H, d, J = 7.2 Hz), 6.81-6.90 (2H, m), 7.11-7.30 (3H, m), 7.78 (2H, m).

参考例２３２で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]アセトアミドおよび2-(2-クロロフェニル)エチルアミンを用い、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点150-151℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.53-1.78 (4H, m), 1.94 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.78-2.98 (6H, m), 3.31 (2H, dd, J = 16.4, 6.8 Hz), 4.53 (1H, br), 4.74 (1H, m), 5.96 (1H, d, J = 7.2 Hz), 7.09-7.34 (5H, m), 7.78 (2H, m). N- [5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide hydrochloride

Using N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 232, Reference Example 19 and The title compound was obtained as colorless crystals having a melting point of 150-151 ° C. by sequentially performing the same operations as in Example 1.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.53-1.78 (4H, m), 1.94 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.60 (2H, m), 2.78- 2.98 (6H, m), 3.31 (2H, dd, J = 16.4, 6.8 Hz), 4.53 (1H, br), 4.74 (1H, m), 5.96 (1H, d, J = 7.2 Hz), 7.09-7.34 (5H, m), 7.78 (2H, m).

参考例２３５で得た2-(2-クロロフェニル)エチル[5-(1,3-ジメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-イル)-5-ヒドロキシペンチル]カルバミン酸tert-ブチル(1.25g) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点253-255℃の無色結晶(340mg)として得た。
¹H NMR (400MHz, CD₃OD) δ 1.32-1.41 (1H, m), 1.46-1.57 (1H, m), 1.68-1.75 (3H, m), 1.83-1.92 (1H, m), 3.01 (2H, t, J = 7.8Hz), 3.12-3.23 (4H, m), 3.40 (3H, s), 3.41 (3H, s), 4.21-4.24 (1H, m), 4.91 (3H, s), 7.08-7.12 (3H, m), 7.27-7.31 (2H, m), 7.37-7.42 (2H, m).
IR (KBr) νcm^-1: 3428, 2944, 1712, 1510, 1462, 747, 584. 5- (5-{[2- (2-chlorophenyl) ethyl] amino} -1-hydroxypentyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

2- (2-Chlorophenyl) ethyl [5- (1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl) -5-hydroxypentyl] carbamine obtained in Reference Example 235 The title compound was obtained as colorless crystals (340 mg) having a melting point of 253-255 ° C. by the same procedure as in Example 1 using tert-butyl acid (1.25 g).
¹ H NMR (400MHz, CD ₃ OD) δ 1.32-1.41 (1H, m), 1.46-1.57 (1H, m), 1.68-1.75 (3H, m), 1.83-1.92 (1H, m), 3.01 (2H , t, J = 7.8Hz), 3.12-3.23 (4H, m), 3.40 (3H, s), 3.41 (3H, s), 4.21-4.24 (1H, m), 4.91 (3H, s), 7.08- 7.12 (3H, m), 7.27-7.31 (2H, m), 7.37-7.42 (2H, m).
IR (KBr) νcm ^-1 : 3428, 2944, 1712, 1510, 1462, 747, 584.

参考例２３６で得た2-(2-クロロ-4-ヒドロキシフェニル)エチル[5-オキソ-5-(4-オキソ-1,2,5,6-テトラヒドロ-4H-ピロロ[3,2,1-ij]キノリン-8-イル)ペンチル]カルバミン酸tert-ブチル(240mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点184-185℃の無色結晶(203mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.62-1.73 (4H, m), 2.58(2H, t, J = 7.8Hz), 2.95-3.01 (10H, m), 3.16 (2H, t, J = 8.3Hz), 3.97 (2H, t, J = 8.3Hz), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.3Hz), 7.71 (1H, s), 7.73 (1H, s), 9.05 (2H, s), 9.89 (1H, br).
IR (KBr) νcm^-1: 2949, 2767, 1642, 1592, 1500, 1455, 1400, 1158, 1042, 852. 8- (5-{[2- (2-chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1-ij] quinoline- 4-one hydrochloride

2- (2-Chloro-4-hydroxyphenyl) ethyl [5-oxo-5- (4-oxo-1,2,5,6-tetrahydro-4H-pyrrolo [3,2,1] obtained in Reference Example 236 -ij] quinolin-8-yl) pentyl] carbylate tert-butyl (240 mg) by the same procedure as in Example 1 to give the title compound as colorless crystals (203 mg) having a melting point of 184-185 ° C. Obtained.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.62-1.73 (4H, m), 2.58 (2H, t, J = 7.8Hz), 2.95-3.01 (10H, m), 3.16 (2H, t, J = 8.3Hz), 3.97 (2H, t, J = 8.3Hz), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.3Hz), 7.71 (1H, s), 7.73 (1H, s), 9.05 (2H, s), 9.89 (1H, br).
IR (KBr) νcm ^-1 : 2949, 2767, 1642, 1592, 1500, 1455, 1400, 1158, 1042, 852.

参考例２３７で得た5-(1-アセチル-2,3-ジヒドロ-1H-インドール-5-イル)-5-オキソペンチル[2-(2-クロロ-4-ヒドロキシフェニル)エチル]カルバミン酸tert-ブチル(320mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点197-199℃の無色結晶(260mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.64-1.79 (4H, m), 2.17 (3H, s), 2.93-3.01 (8H, m), 3.16 (2H, t, J = 8.3Hz), 4.13 (2H, t, J = 8.3Hz), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.87 (1H, d, J = 2.4Hz), 7.15 (1H, d, J = 8.3Hz), 7.81 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.07 (1H, d, J = 8.3Hz), 9.18 (2H, s), 9.51 (1H, br).
IR (KBr) νcm^-1: 2949, 2780, 1686, 1632, 1587, 1503, 1443, 1405, 1248, 826. 1- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-{[2- (2-chloro-4-hydroxyphenyl) ethyl] amino} pentan-1-one hydrochloride

5- (1-acetyl-2,3-dihydro-1H-indol-5-yl) -5-oxopentyl [2- (2-chloro-4-hydroxyphenyl) ethyl] carbamic acid tert obtained in Reference Example 237 The title compound was obtained as colorless crystals (260 mg) having a melting point of 197-199 ° C. by conducting the same operation as in Example 1 using -butyl (320 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.64-1.79 (4H, m), 2.17 (3H, s), 2.93-3.01 (8H, m), 3.16 (2H, t, J = 8.3Hz), 4.13 (2H, t, J = 8.3Hz), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.87 (1H, d, J = 2.4Hz), 7.15 (1H, d, J = 8.3Hz), 7.81 (1H, s), 7.82 (1H, d, J = 8.3Hz), 8.07 (1H, d, J = 8.3Hz), 9.18 (2H, s), 9.51 (1H, br).
IR (KBr) νcm ^-1 : 2949, 2780, 1686, 1632, 1587, 1503, 1443, 1405, 1248, 826.

参考例２３８で得た2-(2-クロロ-4-ヒドロキシフェニル)エチル[5-(1-メチル-2-オキソ-1,2,5,6-テトラヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-8-イル)-5-オキソペンチル]カルバミン酸tert-ブチル(114mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点175-177℃の無色結晶(82mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.68 (4H, br.s), 2.00-2.04 (2H, m), 2.98-3.07 (8H, m), 3.34 (2H, br.s), 3.36 (3H, s), 3.71-3.76 (2H, m), 6.73 (1H, dd, J = 8.5, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.5Hz), 7.59 (2H, s), 9.00 (2H, br.), 9.93 (1H, s).
IR (KBr) νcm^-1: 3426, 2955, 2790, 1698, 1641, 1610, 1501, 1436, 1277, 1251. 8- (5-{[2- (2-chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline- 2 (1H) -one hydrochloride

2- (2-Chloro-4-hydroxyphenyl) ethyl [5- (1-methyl-2-oxo-1,2,5,6-tetrahydro-4H-imidazo [4,5,1] obtained in Reference Example 238 -ij] quinolin-8-yl) -5-oxopentyl] carbamate tert-butyl (114 mg) by performing the same procedure as in Example 1 to obtain the title compound as colorless crystals having a melting point of 175-177 ° C. Obtained as (82 mg).
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.68 (4H, br.s), 2.00-2.04 (2H, m), 2.98-3.07 (8H, m), 3.34 (2H, br.s), 3.36 ( 3H, s), 3.71-3.76 (2H, m), 6.73 (1H, dd, J = 8.5, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 7.16 (1H, d, J = 8.5Hz ), 7.59 (2H, s), 9.00 (2H, br.), 9.93 (1H, s).
IR (KBr) νcm ^-1 : 3426, 2955, 2790, 1698, 1641, 1610, 1501, 1436, 1277, 1251.

参考例２３９で得た2-(2-クロロ-4-ヒドロキシフェニル)エチル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-8-イル)ペンチル]カルバミン酸tert-ブチル(55mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点185-186℃の無色結晶(38mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.66 (4H, br.s), 2.00-2.03 (2H, m), 2.82 (2H, t, J = 6.0Hz), 2.97-3.02 (8H, m), 3.42 (1H, br.), 3.71 (2H, t, J = 6.0Hz), 6.73 (1H, dd, J = 8.3, 2.2Hz), 6.85 (1H, d, J = 2.2Hz), 7.16 (1H, d, J = 8.3Hz), 7.38 (1H, s), 7.55 (1H, s), 8.91 (2H, br.s), 9.91 (1H, s).
IR (KBr) νcm^-1: 3252, 2959, 2815, 1717, 1664, 1613, 1502, 1439, 1150, 668. 8- (5-{[2- (2-Chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H) -On hydrochloride

2- (2-Chloro-4-hydroxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-imidazo [4,5,1] obtained in Reference Example 239 -ij] quinolin-8-yl) pentyl] carbylate tert-butyl (55 mg) by performing the same procedure as in Example 1 to obtain the title compound as colorless crystals (38 mg) having a melting point of 185-186 ° C. Obtained.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.66 (4H, br.s), 2.00-2.03 (2H, m), 2.82 (2H, t, J = 6.0Hz), 2.97-3.02 (8H, m) , 3.42 (1H, br.), 3.71 (2H, t, J = 6.0Hz), 6.73 (1H, dd, J = 8.3, 2.2Hz), 6.85 (1H, d, J = 2.2Hz), 7.16 (1H , d, J = 8.3Hz), 7.38 (1H, s), 7.55 (1H, s), 8.91 (2H, br.s), 9.91 (1H, s).
IR (KBr) νcm ^-1 : 3252, 2959, 2815, 1717, 1664, 1613, 1502, 1439, 1150, 668.

参考例２４０で得た2-(2-クロロ-4-ヒドロキシフェニル)エチル[5-オキソ-5-(2-オキソ-1,2,5,6-テトラヒドロ-4H-イミダゾ[4,5,1-ij]キノリン-9-イル)ペンチル]カルバミン酸tert-ブチル(64mg) を用いて、実施例１と同様の操作を行うことにより、表題化合物を融点173-175℃の無色結晶(44mg)として得た。
¹H NMR (400MHz, DMSO-d₆) δ 1.68 (4H, br.s), 1.99-2.02 (2H, m), 2.82 (2H, t, J = 6.0Hz), 2.97-3.03 (8H, m), 3.71 (2H, t, J = 6.0Hz), 4.24 (1H, br.), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 6.91 (1H, d, J = 8.3Hz), 7.16 (1H, d, J = 8.0Hz), 7.53 (1H, d, J = 8.0Hz), 8.90 (2H, br.s), 10.82 (1H, s).
IR (KBr) νcm^-1: 3152, 2958, 1689, 1610, 1502, 1488, 1442, 1229, 1041, 692. 9- (5-{[2- (2-chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H) -On hydrochloride

2- (2-Chloro-4-hydroxyphenyl) ethyl [5-oxo-5- (2-oxo-1,2,5,6-tetrahydro-4H-imidazo [4,5,1] obtained in Reference Example 240 -ij] quinolin-9-yl) pentyl] carbylate tert-butyl (64 mg) by the same procedure as in Example 1 to give the title compound as colorless crystals (44 mg) having a melting point of 173-175 ° C. Obtained.
¹ H NMR (400MHz, DMSO-d ₆ ) δ 1.68 (4H, br.s), 1.99-2.02 (2H, m), 2.82 (2H, t, J = 6.0Hz), 2.97-3.03 (8H, m) , 3.71 (2H, t, J = 6.0Hz), 4.24 (1H, br.), 6.73 (1H, dd, J = 8.3, 2.4Hz), 6.85 (1H, d, J = 2.4Hz), 6.91 (1H , d, J = 8.3Hz), 7.16 (1H, d, J = 8.0Hz), 7.53 (1H, d, J = 8.0Hz), 8.90 (2H, br.s), 10.82 (1H, s).
IR (KBr) νcm ^-1 : 3152, 2958, 1689, 1610, 1502, 1488, 1442, 1229, 1041, 692.

参考例２４１で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]アセトアミドおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.53-1.80 (4H, m), 2.15 (3H, s), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.61 (2H, m), 2.81 (3H, s), 2.85-2.98 (6H, m), 3.18 (2H, dd, J = 16.4, 6.8 Hz), 5.32 (1H, m), 7.08-7.38 (5H, m), 7.78 (2H, m). N- (5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) acetamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide and N- [2- (2-chlorophenyl) ethyl] -N— obtained in Reference Example 241 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9 using methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.53-1.80 (4H, m), 2.15 (3H, s), 2.34 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.61 ( 2H, m), 2.81 (3H, s), 2.85-2.98 (6H, m), 3.18 (2H, dd, J = 16.4, 6.8 Hz), 5.32 (1H, m), 7.08-7.38 (5H, m) , 7.78 (2H, m).

参考例２４１で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]アセトアミドおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.55-1.80 (4H, m), 2.15 (3H, s), 2.34 (3H, s), 2.47 (2H, t, J = 7.2Hz), 2.58 (2H, m), 2.72-2.82 (4H, m), 2.80 (3H, s), 2.96 (2H, t, J = 7.0Hz), 3.25 (2H, dd, J = 17.0, 8.8Hz), 3.80 (3H, s), 5.25 (1H, m), 6.80-6.88 (2H, m), 7.11-7.18 (2H, m), 7.28 (1H, m), 7.79 (2H, m). N- (5- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) acetamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide and N- [2- (2-methoxyphenyl) ethyl] -N obtained in Reference Example 241 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9 using methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.55-1.80 (4H, m), 2.15 (3H, s), 2.34 (3H, s), 2.47 (2H, t, J = 7.2 Hz), 2.58 ( 2H, m), 2.72-2.82 (4H, m), 2.80 (3H, s), 2.96 (2H, t, J = 7.0Hz), 3.25 (2H, dd, J = 17.0, 8.8Hz), 3.80 (3H , s), 5.25 (1H, m), 6.80-6.88 (2H, m), 7.11-7.18 (2H, m), 7.28 (1H, m), 7.79 (2H, m).

参考例２４１で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]アセトアミドおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を融点137-138℃の無色結晶として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.53-1.79 (4H, m), 2.15 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.61 (2H, m), 2.81 (3H, s), 2.85-2.98 (6H, m), 3.18 (2H, dd, J = 16.4, 6.8 Hz), 4.28 (1H, br), 5.32 (1H, m), 7.09-7.37 (5H, m), 7.78 (2H, m). N- [5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide hydrochloride

Using N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] acetamide and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 241, Reference Example 19 The title compound was obtained as colorless crystals having a melting point of 137-138 ° C. by sequentially performing the same operations as in Example 1.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.53-1.79 (4H, m), 2.15 (3H, s), 2.48 (2H, t, J = 7.4 Hz), 2.61 (2H, m), 2.81 ( 3H, s), 2.85-2.98 (6H, m), 3.18 (2H, dd, J = 16.4, 6.8 Hz), 4.28 (1H, br), 5.32 (1H, m), 7.09-7.37 (5H, m) , 7.78 (2H, m).

参考例２４２で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]メタンスルホンアミドおよびN-[2-(2-クロロフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.55-1.77 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.6 Hz), 2.61 (2H, m), 2.71 (3H, s), 2.89 (3H, s), 2.91-3.10 (6H, m), 3.35 (2H, dd, J = 16.8, 8.4 Hz), 4.90 (1H, quint, J = 7.0 Hz ), 7.09-7.32 (5H, m), 7.78 (2H, m). N- (5- {5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) methanesulfonamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide and N- [2- (2-chlorophenyl) ethyl]-obtained in Reference Example 242 The title compound was obtained as a colorless amorphous powder by performing the same operation as in Example 9 using N-methylamine.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.55-1.77 (4H, m), 2.34 (3H, s), 2.48 (2H, t, J = 7.6 Hz), 2.61 (2H, m), 2.71 ( 3H, s), 2.89 (3H, s), 2.91-3.10 (6H, m), 3.35 (2H, dd, J = 16.8, 8.4 Hz), 4.90 (1H, quint, J = 7.0 Hz), 7.09-7.32 (5H, m), 7.78 (2H, m).

参考例２４２で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]メタンスルホンアミドおよびN-[2-(2-メトキシフェニル)エチル]-N-メチルアミンを用いて、実施例９と同様の操作を行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.54-1.79 (4H, m), 2.33 (3H, s), 2.48 (2H, t, J = 7.0 Hz), 2.58 (2H, m), 2.71 (3H, s), 2.80 (2H, m), 2.89 (3H, s), 2.96 (2H, m), 3.05 (2H, m), 3.28 (2H, dd, J = 16.4, 8.0 Hz), 3.81 (3H, s), 4.91 (1H, m), 6.81-6.90 (2H, m), 7.12-7.31 (3H, m), 7.78 (2H, m). N- (5- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -2,3-dihydro-1H-inden-2-yl) methanesulfonamide hydrochloride

N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide and N- [2- (2-methoxyphenyl) ethyl] obtained in Reference Example 242 The title compound was obtained as a colorless amorphous powder by conducting the same operation as in Example 9 using -N-methylamine.
¹ H NMR (free _{base; 200MHz, CDCl 3) δ 1.54-1.79} (4H, m), 2.33 (3H, s), 2.48 (2H, t, J = 7.0 Hz), 2.58 (2H, m), 2.71 ( 3H, s), 2.80 (2H, m), 2.89 (3H, s), 2.96 (2H, m), 3.05 (2H, m), 3.28 (2H, dd, J = 16.4, 8.0 Hz), 3.81 (3H , s), 4.91 (1H, m), 6.81-6.90 (2H, m), 7.12-7.31 (3H, m), 7.78 (2H, m).

参考例２４２で得たN-[5-(5-クロロペンタノイル)-2,3-ジヒドロ-1H-インデン-2-イル]メタンスルホンアミドおよび2-(2-クロロフェニル)エチルアミンを用いて、参考例１９および実施例１と同様の操作を順次行うことにより、表題化合物を無色非晶状粉末として得た。
¹H NMR (フリー塩基; 200MHz, CDCl₃) δ 1.55-1.77 (4H, m), 2.47 (2H, t, J = 7.4 Hz), 2.61 (2H, m), 2.71 (3H, s), 2.89 (3H, s), 2.91-3.10 (6H, m), 3.35 (2H, dd, J = 16.4, 8.0 Hz), 4.08 (1H, br), 4.90 (1H, quint, J = 7.0 Hz ), 7.09-7.32 (5H, m), 7.78 (2H, m). N- [5- (5-{[2- (2-Chlorophenyl) ethyl] amino} pentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide hydrochloride

Using N- [5- (5-chloropentanoyl) -2,3-dihydro-1H-inden-2-yl] methanesulfonamide and 2- (2-chlorophenyl) ethylamine obtained in Reference Example 242, The title compound was obtained as a colorless amorphous powder by sequentially performing the same operations as in Example 19 and Example 1.
¹ H NMR (free base; 200 MHz, CDCl ₃ ) δ 1.55-1.77 (4H, m), 2.47 (2H, t, J = 7.4 Hz), 2.61 (2H, m), 2.71 (3H, s), 2.89 ( 3H, s), 2.91-3.10 (6H, m), 3.35 (2H, dd, J = 16.4, 8.0 Hz), 4.08 (1H, br), 4.90 (1H, quint, J = 7.0 Hz), 7.09-7.32 (5H, m), 7.78 (2H, m).

Formulation Example 1

(1) 1 g of the compound of Example 20
(2) Lactose 197g
(3) Corn starch 50g
(4) Magnesium stearate 2g
Mix (1), (2) and corn starch (20 g), granulate with corn starch (15 g) and paste made from 25 mL water, add corn starch (15 g) and (4) above, The mixture was compressed in a compression tablet machine to produce 2000 3 mm diameter tablets containing 0.5 mg of the compound of Example 20 per tablet.

Formulation Example 2

(1) Compound 20g of Example 20
(2) Lactose 197g
(3) Corn starch 50g
(4) Magnesium stearate 2g
In the same manner as in Formulation Example 1, 2000 3 mm diameter tablets containing 1.0 mg of the compound of Example 20 per tablet were produced.

Formulation Example 3

(1) Compound of Example 20 5.0 mg
(2) Lactose 60.0mg
(3) Corn starch 35.0mg
(4) Gelatin 3.0mg
(5) Magnesium stearate 2.0mg
The mixture of (1), (2) and (3) above was granulated through a 1 mm mesh sieve using 0.03 ml of 10% aqueous gelatin solution (3.0 mg as gelatin), dried at 40 ° C., and again Sifted. The obtained granule was mixed with the above (5) and compressed. The obtained central tablet was coated with a sugar coating using a water suspension of sucrose, titanium dioxide, talc and gum arabic. Coated tablets were obtained by polishing the coated tablets with beeswax.

Experimental example 1

a) Measurement of acetylcholinesterase inhibitory activity The acetylcholinesterase inhibitory activity of the example compounds was measured by the acetylthiocholine method (Ellman method) using human erythrocyte-derived acetylcholinesterase.
Human erythrocyte-derived acetylcholinesterase (Sigma) was dissolved in distilled water to a concentration of 0.2 IU / mL to prepare an enzyme preparation. Dispense 20 μL of chemical solution, 30 μL of 80 mM Tris-HCl (pH 7.4), 50 μL of enzyme preparation and 50 μL of 5 mM 5,5-dithio-bis (2-nitrobenzoic acid) (Sigma) into a 96-well microplate for 10 seconds. Shake. 50 μL of 4 mM acetylthiocholine iodide (Sigma) was added, and immediately after shaking again, the increase in absorbance at 414 nM was measured at 30-second intervals for 10 minutes. The enzyme activity was measured by the following formula.
R = 5.74 × 10 ⁻⁷ × Δ _A
(Wherein, R enzyme activity (mol), the delta _A shows the absorbance increase of 414 nm)
The experiment was repeated at least three times for each compound to determine the 50% inhibitory concentration (IC ₅₀ ). In the same manner as described above, the acetylcholinesterase inhibitory activity of distigmine, a known acetylcholinesterase inhibitor, was measured.

b) Measurement of α _1A receptor binding inhibitory activity The gene manipulation method described below is the method described in the book (Maniatis et al., Molecular Cloning, Cold Spring Harbor Laboratory, 1989) or the protocol attached to the reagent. The method described was followed.
(I) was cloned adrenergic alpha _1A receptor gene by the PCR method from an expression plasmid prepared human liver cDNA for human adrenergic alpha _1A receptor. Adrenaline α _1A receptor gene base reported by Hirasawa A. et al. (Biochem. Biophys. Res. Commun., 195, 902-909 (1993)) using 200 ng of human liver cDNA library (Takara Shuzo) as a template. Primer set prepared with reference to the sequence 5'-CCGAATTCGGCTGGGACCATGGTGTTTCTC-3 '[SEQ ID NO: 1] and 5'-CTGTCGACCTTTCCTGTCCTAGACTTCCTC-3' [SEQ ID NO: 2] were added at 50 pmol each, and TaKaRa Pyrobest DNA Polymerase (Takara Shuzo) was used. Then, the PCR reaction was performed with Gene Amp PCR System 9700 (Applied Biosystems) (reaction conditions: 45 cycles of 94 ° C. for 15 seconds and 68 ° C. for 3 minutes 30 seconds).
The PCR fragment obtained above was digested with restriction enzymes Eco RI (Takara Shuzo) and Sal I (Takara Shuzo), and then subjected to agarose gel electrophoresis to recover the DNA fragment. The DNA fragment was mixed with an expression plasmid pMSRαneo (control number A99-0013) for animal cells digested with Eco RI and Sal I, and DNA Ligation Kit Ver. 2 (Takara Shuzo) was ligated with the competent cells of Escherichia coli JM109 to obtain plasmid pMSRαneo-Adreα _1A by transforming.

(Ii) Introduction of human adrenaline α _1A receptor expression plasmid into CHO-K1 cells and preparation of membrane fraction
CHO-K1 cells subcultured in a 150 cm ² culture flask (Corning Coaster) using Ham's F12 medium (Invitrogen) containing 10% fetal calf serum (TRACE SCIENCETIFIC) 0.5 g / L trypsin-0.2 g / After peeling off with L EDTA (Invitrogen), the cells were washed with D-PBS (-) (Invitrogen), centrifuged (1000 rpm, 5 minutes), and suspended in D-PBS (-). Next, DNA was introduced into the cells using Gene Pulser (BioRad) according to the following conditions. Specifically, 1 × 10 ⁷ cells suspended in 700 μl of D-PBS (−) and 10 μg of pMSRαneo-Adreα _1A were added to a 0.4 cm gap cuvette (BioRad), and electroporation was performed at a voltage of 0.25 kV and a capacitance of 960 μF. Carried out. Thereafter, the cells are transferred to Ham's F12 medium containing 10% fetal calf serum, cultured for 24 hours, detached and centrifuged again, and then Ham's F12 containing 10% fetal calf serum and 500 μg / ml geneticin (Invitrogen). Using a culture medium, seeding was carried out at 1000 cells / well in a 96-well plate (Corning) and cultured for 10 days to obtain a geneticin resistant strain.
A plurality of geneticin-resistant strains thus obtained were selected, and each strain was cultured in a cell culture flask at 150 cm ² until it became semiconfluent, and a cell membrane fraction was prepared as follows.
Peel semiconfluent cells with D-PBS (-) containing 0.02% EDTA, collect the cells by centrifugation, and prepare the membrane preparation buffer (50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 10 mM magnesium chloride). , 0.25 mM PMSF, 1 μg / ml pepstatin, 20 μg / ml leupeptin, 0.5% BSA), and treated with Polytron homogenizer (model PT-3000, KINEMATICA AG) for 20 seconds 3 times at 20000 rpm Cells were disrupted. After cell disruption, centrifugation was performed at 2000 rpm for 10 minutes to obtain a supernatant containing a membrane fraction. The supernatant was centrifuged at 30000 rpm for 1 hour at an ultracentrifuge (model L8-70M, rotor 70Ti, Beckman) to obtain a precipitate containing a membrane fraction. The obtained membrane fraction of each clone was subjected to the following binding experiment.
Membrane fraction diluted with membrane preparation buffer (100 μg / ml) and ligand [ ³ H] -Prazosin (2.5 nM, NEN Life Science Products) were added to 96-well microplate and allowed to react at room temperature for 1 hour. It was. For measurement of non-specific binding, Prazosin (Sigma) was further added to 10 μM. Next, the membrane fraction was transferred to a unifilter GF / C (Packard) by filtering the reaction solution using a cell harvester (Packard) and washed three times with ice-cooled 50 mM Tris buffer (pH 7.5). . After drying the filter, microcinch 0 (Packard) was added to the filter, and the radioactivity was measured with a top count (Packard). Using the strain that showed the best S / B value (total bound radioactivity / non-specific bound radioactivity) in the binding measurement using the membrane fraction, the membrane fraction for compound evaluation shown below was It prepared by the same method and used for the following compound evaluation.

(Iii) Evaluation of Example Compounds
Membrane fraction diluted with membrane preparation buffer (100 μg / ml), compound and [ ³ H] -Prazosin (2.5 nM, NEN Life Science Products) were added to a 96-well microplate and reacted at room temperature for 1 hour. . For measurement of non-specific binding, cold ligand Prazosin (Sigma) was further added to 10 μM. Next, the membrane fraction was transferred to Unifilter GF / C (Packard) by filtering the reaction solution using a cell harvester (Packard), and washed three times with cooled 50 mM Tris buffer (pH 7.5). After drying the filter, microcinch 0 (Packard) was added to the filter, and the radioactivity was measured with a top count (Packard).
The concentration of compound (IC ₅₀ ) required to reduce the amount of [ ³ H] -Prazosin bound to the membrane fraction to 50% was calculated using PRISM 2.01 (GraphPad Software). The IC ₅₀ of urapidil (hydrochloride), a known α ₁ receptor antagonist, was determined in the same manner.
The results measured by the above methods a) and b) are shown in the following table.

上記の結果より、本発明化合物（Ｉ）は優れたアセチルコリンエステラーゼ阻害作用を有し、かつ優れたα_1A受容体結合阻害活性を併有することがわかる。 [Table 1]

From the above results, it can be seen that the compound (I) of the present invention has an excellent acetylcholinesterase inhibitory action and also has an excellent α _1A receptor binding inhibitory activity.

Experimental example 2

a) Effects on phenylephrine-loaded guinea pigs on maximum urinary flow rate, intravesical pressure and micturition efficiency (Pressure Flow Study)
A Hartley male guinea pig (Slc) weighing 300-350 g was anesthetized with urethane (1.2 g / kg, ip), and the midline was incised to expose the bladder. Two polyethylene tubes were inserted into the urinary bladder, one was used for injection of physiological saline, and the other was used for measurement of intravesical pressure. The left femoral vein was cannulated and phenylephrine was administered intravenously at 3 μg / animal / min continuously until the end of the experiment. Saline was injected into the bladder at a rate of 0.3 mL / min, and the injection was stopped when urination was confirmed. The weight of urinated urine was measured in real time with an electronic balance (HX-400, A & D). Analog data of intravesical pressure and urine weight were input to an AD converter (MP-100, BIOPAC Systems), and digital signals were analyzed with dedicated analysis software (AcqKnowledge 3.5.3, BIOPAC Systems). The sampling rate of the data was 10 Hz, and the urine output and urine flow rate data were subjected to a low cut filter at 0.5 Hz to remove noise. The urine flow rate (Q) was calculated by differentiating the value of urine weight, and the maximum urinary flow rate (Qmax) at the time of urination and the intravesical pressure (Pves (Qmax)) at the time of the maximum urine flow were obtained. The amount of urination was calculated by converting 1 g of urine weight to 1 mL, and dividing the urine volume by the bladder capacity. Example compounds were dissolved in DMSO and administered intravenously at 0.5 mL / kg. The micturition reflex was recorded again 10 minutes after administration of the test compound, and the urinary efficiency was evaluated by the change in urinary flow rate (ΔQmax) and the change in intravesical pressure (ΔPves (Qmax)). Change in urinary flow rate (ΔQmax) and change in intravesical pressure (ΔPves (Qmax)) are the amount of change (Δ value) obtained by subtracting each value before administration from the value after administration of the test compound. The efficiency was evaluated by the relative value (% of pre-value) after administration to the test compound administration. The same measurement was performed for tamsulosin, which is a known α ₁ receptor antagonist. A significant difference was tested by Dunnett's test in comparison with each value of the vehicle (DMSO) administration group.

b) Effects on blood pressure A Hartley male guinea pig (Slc) having a body weight of 300 to 350 g was anesthetized with urethane (1.2 g / kg) and then retained, and the neck was incised to expose the left common carotid artery. A polyethylene tube filled with physiological saline containing heparin (10 UI / ml) was inserted into the artery, and blood pressure was measured with a pressure transducer. A cannula was inserted into the vein at the end of the left hind limb for administration of the test compound, from which the test compound dissolved in distilled water was administered at 0.5 mL / kg. Blood pressure was recorded at 20 Hz using an analog data capture device (MP-100, BIOPAC Systems) and analyzed with analysis software (AcqKnowledge 3.5.3, BIOPAC Systems). Example compounds and tamsulosin were examined for doses at which an effect was observed in the test a (Pressure Flow Study), and the average blood pressure immediately before administration of the test compound and the average blood pressure 15 minutes after administration were measured. Statistical processing was performed by Paired t-test.
The following table summarizes the results of Pressure Flow Study of the compound of the present invention and tamsulosin and the effect on blood pressure.

[Table 2]
Effect of the compound of the present invention and tamsulosin on the maximum urinary flow rate change (ΔQmax), intravesical pressure change (ΔPves (Qmax)) and urination efficiency

[Table 3]
Effects of the compound of the present invention and tamsulosin on blood pressure

Based on the above results, the α ₁ receptor antagonist tamsulosin (0.01 mg / kg, iv) significantly reduced the intravesical pressure and significantly increased the maximum urinary flow rate and micturition efficiency. It can be seen that it decreases by about 40%. On the other hand, the compound of the present invention (0.1 mg / kg, iv) significantly increases urinary flow rate and urination efficiency without significantly lowering the intravesical pressure, and does not affect blood pressure at the same dose. .
From the results of the above Experimental Examples 1 and 2, it can be seen that the compound of the present invention having both an acetylcholinesterase inhibitory action and an α ₁ antagonistic action has an excellent preventive / therapeutic action for dysuria, particularly difficulty in urination.
In addition, the in vivo evaluation method by pressure flow study using phenylephrine-loaded guinea pig shown in Experimental Example 1a can simultaneously and appropriately evaluate the effects of the compound of the present invention and tamsulosin on the maximum urinary flow rate, intravesical pressure and urination efficiency. It was. This shows that this method is useful as a method for evaluating a therapeutic agent for dysuria associated with benign prostatic hyperplasia.

A compound having both an acetylcholinesterase inhibitory action and an α ₁ antagonistic action used in the present invention has an excellent effect of improving bladder urination function (an effect of improving urinary flow rate and efficiency), and also has an effect on urination pressure and blood pressure. Therefore, it is useful as a preventive or therapeutic agent for dysuria.
In addition, the screening method of the present invention, in which the pressure flow study is applied to an animal model loaded with an α agonist (phenylephrine), is useful as an excellent screening method for a compound having a urinary dysfunction prevention or treatment associated with prostatic hypertrophy or a salt thereof. is there.

Claims (48)

  A preventive or therapeutic agent for dysuria, comprising a compound having both an acetylcholinesterase inhibitory action and an α1 antagonistic action. Formula that has both acetylcholinesterase inhibitory action and α1 antagonistic action

[In the formula, Ar represents an optionally condensed 5- or 6-membered aromatic ring group, the aromatic ring group may have a substituent, and L may have a substituent. 1 to 10 of the above spacers may be formed, or a ring may be formed with Ar, and Y may have an amino group or a substituent which may have a substituent. A nitrogen-containing heterocyclic group is shown. The agent of Claim 1 containing the compound or its salt represented by these, or its prodrug. The agent according to claim 2, wherein L is a C _1-10 alkylene group which may have a substituent.   The agent according to claim 1, which is a preventive or therapeutic agent for dysuria associated with benign prostatic hyperplasia. The agent according to claim 1, wherein the compound has an IC ₅₀ value of about 1: 100 to about 100: 1 for the acetylcholinesterase inhibitory action and the α1 antagonistic action of the compound. The agent according to claim 1, wherein the compound has an IC ₅₀ value of about 1: 1 to about 30: 1 for each of acetylcholinesterase inhibitory action and α1 antagonistic action of the compound.   The agent according to claim 1, which does not show a decrease in blood pressure at a dose exhibiting an effect of improving urinary flow rate.   The agent according to claim 7, wherein the urinary flow rate after administration is improved by about 20% or more compared to before administration, and the blood pressure decrease after administration is within about 10% compared to before administration.   The agent according to claim 1, which does not show a decrease in blood pressure at a dose exhibiting an effect of improving urination efficiency.   The agent according to claim 9, wherein the urination efficiency after administration is improved by about 10% or more compared to before administration, and the blood pressure decrease after administration is within about 10% compared to before administration.   The agent according to claim 1, which is not accompanied by orthostatic hypotension.   A method for preventing and treating dysuria, comprising administering an effective amount of a compound having both an acetylcholinesterase inhibitory action and an α1 antagonistic action to a mammal.   Use of a compound having both an acetylcholinesterase inhibitory action and an α1 antagonistic action in the production of a preventive or therapeutic agent for dysuria. formula

[In the formula, Ar ₁ represents an optionally substituted bicyclic to tetracyclic fused benzene ring group (excluding the 2,3-dihydro-1-benzofuran ring group), and L ₁ represents a substituted group. A C _4-6 alkylene group which may have a group, L ₂ represents a C _2-4 alkylene group which may have a substituent, and R has a hydrogen atom or a substituent, X may be a bond, an oxygen atom, or NR ^1a (R ^1a may be a hydrogen atom, a hydrocarbon group that may have a substituent, an acyl group, or a substituent. Ar ₂ represents an aromatic ring group which may have a substituent, or Ar ₂ and R or Ar ₂ and L ₂ are bonded to each other to form a ring. It may be. Or a salt thereof. Ar ₁ is the formula

[In the formula, A ring represents an optionally substituted benzene ring, and B ring represents an optionally substituted homocyclic or heterocyclic ring (provided that 2,3-dihydrofuran). One of C ring and D ring represents a heterocyclic ring which may have a substituent, and the other represents a 5- to 9-membered ring which may have a substituent. And at least one of the G rings represents a heterocyclic ring which may have a substituent, and the other rings represent a 5- to 9-membered ring which may have a substituent. The compound of Claim 14 which is group represented by these. Ar ₁ is the formula

[In the formula, A ring represents an optionally substituted benzene ring, Ba ring represents an optionally substituted homocyclic ring or heterocyclic ring, and C ″ ring and D ″ ring represent Each represents a nitrogen-containing heterocyclic ring which may have a substituent, and R ¹ and R ^{1 ′} each have a hydrogen atom, a hydrocarbon group which may have a substituent, an acyl group or a substituent; The heterocyclic group which may be sufficient is shown. The compound of Claim 14 which is group represented by these. Ring A may have 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. In the benzene ring, the Ba ring, the C ″ ring and the D ″ ring each have 1 or 2 substituents selected from C _1-6 alkyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. R ¹ and R ^{1 ′} may each have (1) a hydrogen atom, and (2) each have one or two substituents selected from hydroxy and C _1-6 alkoxy-carbonyl. A C _1-6 alkyl group or a C _7-16 aralkyl group or (3) a formula — (C═O) —R ^{2 ′} , — (C═O) —NR ^{2 ′} R ^{3 ′} or —SO ₂ R ^{2 ′} [ Where R ^{2 ′} and R ^{3 ′} are Each represents a hydrogen atom, C _1-6 alkyl or C _6-10 aryl which may be halogenated. The compound of Claim 16 which is group represented by these. The compound according to claim 14, wherein R is a hydrogen atom or a C _1-4 alkyl group. The compound according to claim 14, wherein L ₁ is a C _4-5 alkylene group, and L ₂ is a C _2-3 alkylene group optionally having phenyl, hydroxy or oxo. Ar ₂ has 1 to 3 substituents each selected from halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, optionally halogenated C _1-6 alkoxy, and aminosulfonyl. A C _6-10 aryl group or a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom (even if the benzene ring is condensed) 15. A compound according to claim 14 which is good. A ring formed by combining Ar ₂ and R with each other has the formula

[Wherein, p and q each represent an integer of 1 to 3, and the H ring is selected from halogen, hydroxy, optionally halogenated C _1-6 alkyl and optionally halogenated C _1-6 alkoxy. A benzene ring optionally having 1 to 3 substituents is shown. A ring formed by combining Ar ₂ and L ₂ with each other is represented by the formula:

[Wherein, r represents an integer of 0 to 2, s represents an integer of 1 to 3, and r + s represents an integer of 2 to 5, and the H ring is halogen, hydroxy, C ₁₋ which may be halogenated. ₆ represents a benzene ring optionally having 1 to 3 substituents selected from alkyl and optionally halogenated C _1-6 alkoxy. The compound of Claim 14 which is a ring represented by this. formula

Wherein, Ar ₃ good benzimidazole ring group which may have a substituent, respectively, a quinazoline ring group, a 1,4-benzoxazine ring group or a tricyclic or tetracyclic condensed benzene ring group, L _{3 Represents a} C _2-4 alkylene group which may have a substituent, L ₂ represents a C _2-4 alkylene group which may have a substituent, and X represents a bond, an oxygen atom or NR ^1a (R ^1a represents a hydrogen atom, a hydrocarbon group which may have a substituent, an acyl group or a heterocyclic group which may have a substituent), and Ar ₂ has a substituent An aromatic ring group that may be present, or Ar ₂ and L ₂ may be bonded to each other to form a ring. Or a salt thereof. Ar ₃ is the formula

[Wherein, A ring represents a benzene ring which may have a substituent, and C ′ ring and D ′ ring each represent a nitrogen-containing heterocyclic ring which may have a substituent other than an oxo group. The compound of Claim 22 which is group represented by these. L ₃ is ethylene group, L ₂ is phenyl, hydroxy or a good C _2-3 alkylene group optionally having oxo compound of claim 22, wherein X is a bond or an oxygen atom. Ar ₂ has 1 to 3 substituents each selected from halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, optionally halogenated C _1-6 alkoxy, and aminosulfonyl. A C _6-10 aryl group or a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom (even if the benzene ring is condensed) The ring formed by combining Ar ₂ and L ₂ with each other has the formula

[Wherein, r represents an integer of 0 to 2, s represents an integer of 1 to 3, and r + s represents an integer of 2 to 5, and the H ring is halogen, hydroxy, C ₁₋ which may be halogenated. ₆ represents a benzene ring optionally having 1 to 3 substituents selected from alkyl and optionally halogenated C _1-6 alkoxy. The compound of Claim 22 which is a ring represented by this. formula

[Wherein Ar ₄ represents one or two substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino. And a benzene ring group which may further have 1 to 4 substituents, L ₁ represents a C _4-6 alkylene group which may have a substituent, and L ₂ represents a substituent. the show good C _2-4 alkylene group which may have, R represents a hydrogen atom or may have a substituent hydrocarbon group, X is a bond, an oxygen atom or NR 1a ^{(R 1a} A hydrogen atom, a hydrocarbon group optionally having substituent (s), an acyl group or a heterocyclic group optionally having substituent (s)), and Ar ₂ optionally having a substituent. Represents an aromatic ring group, or Ar ₂ and R, or Ar ₂ and L ₂ may be bonded to each other to form a ring. Or a salt thereof. Ar ₄ has 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, C _1-6 alkyl-carbonylamino and C _1-6 alkylsulfonylamino, A benzene ring group optionally having 1 or 2 C _1-4 alkoxy, L ₁ is a C _4-5 alkylene group, and L ₂ is optionally having hydroxy or oxo C _2-3 An alkylene group, R is a hydrogen atom or a C _1-4 alkyl group, X is a bond, Ar ₂ is halogen, nitro, hydroxy, C _1-6 alkyl which may be halogenated, halogenated A C _6-10 aryl group or a nitrogen atom, an oxygen atom and a sulfur atom which may have 1 to 3 substituents selected from C _1-6 alkoxy and aminosulfonyl which may be 27. The compound according to claim 26, which is a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms selected from: (a benzene ring may be condensed). formula

[Wherein, R ¹ and R ^{1 ′} each represent a hydrogen atom, a hydrocarbon group optionally having substituent (s), an acyl group or a heterocyclic group optionally having substituent (s), and n is 1 or L ₄ represents an integer, L ₄ represents an _optionally substituted C _3-5 alkylene group, L ₂ represents an optionally substituted C _2-4 alkylene group, and R represents A hydrogen atom or a hydrocarbon group which may have a substituent, X is a bond, oxygen atom or NR ^1a (R ^1a is a hydrogen atom, a hydrocarbon group which may have a substituent, an acyl group; Or a heterocyclic group which may have a substituent.) And Ar ₂ represents an aromatic group which may have a substituent, or Ar ₂ and R, or Ar ₂ and L. ₂ may be bonded to each other to form a ring. Or a salt thereof. R ¹ and R ^{1 ′} are each a hydrogen atom or an optionally halogenated C _1-6 alkyl group, L ₄ is a C _3-4 alkylene group, and L ₂ may have hydroxy or oxo A C _2-3 alkylene group, R is a hydrogen atom or a C _1-4 alkyl group, X is a bond, and Ar ₂ is halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, it 1 selected from halogenated optionally C _1-6 alkoxy and aminosulfonyl may have three substituents, selected C _6-10 aryl group or a nitrogen atom, oxygen atom and sulfur atom 29. The compound according to claim 28, which is a 5- or 6-membered aromatic heterocyclic group containing 1 to 4 heteroatoms (which may be condensed with a benzene ring). 8- (5-[[2- (2-Chlorophenyl) ethyl] amino] pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one or a salt thereof ,
5- [5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
1,3-dimethyl-5- [5-({2- [2- (trifluoromethoxy) phenyl] ethyl}
Amino) pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
8- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H)- On or its salt,
8- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -1-methyl-5,6-dihydro-4H-imidazo [4,5,1-ij] quinoline-2 (1H) -one or a salt thereof,
1,3-dimethyl-5- [5-({2- [2- (trifluoromethoxy) phenyl] ethy} amino) pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
8- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -5,6-dihydro-4H-pyrrolo [3,2,1-ij] quinolin-2 (1H) -one or a salt thereof Or
15. It is 5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof. Compound.   29. A prodrug of the compound according to claim 14, 22, 26 or 28 or a salt thereof. formula

[Wherein, Z ₁ is a leaving group, and other symbols are as defined in claim 14. Or a salt thereof, and a formula

[Wherein each symbol has the same meaning as in claim 14. ] The compound or its salt represented by these is made to react, The manufacturing method of the compound of Claim 14 characterized by the above-mentioned. Formula _Ar 1 -H
[Wherein Ar ₁ is as defined in claim 14. Or a salt thereof, and a formula

[Wherein, Z ₁ and Z ₂ each represent a leaving group, and L ₁ has the same meaning as defined in claim 14. A compound represented by the formula:

[Wherein each symbol is as defined above. ] The manufacturing method of the compound represented by these, or its salt.   The production method according to claim 33, wherein zinc chloride is used as a catalyst and nitroalkane is used as a solvent.   A medicament comprising the compound according to claim 14, 22, 26 or 28, a salt thereof or a prodrug thereof.   36. The medicament according to claim 35, which is an agent for preventing or treating urination disorder.   36. The medicament according to claim 35, which is a preventive or therapeutic agent for dysuria associated with benign prostatic hyperplasia.   The medicament according to claim 37, which is a prophylactic / therapeutic agent for dysuria due to low tension bladder.   A method for preventing / treating dysuria, comprising administering an effective amount of the compound according to claim 14, 22, 26 or 28, a salt thereof or a prodrug thereof to a mammal.   Use of the compound according to claim 14, 22, 26 or 28, or a salt thereof or a prodrug thereof in the manufacture of a preventive or therapeutic agent for urination disorder.   A screening method for a compound having a urinary dysfunction preventive or therapeutic action by pressure flow study or a salt thereof, characterized by using an animal model loaded with an α agonist.   The screening method according to claim 41, wherein the α agonist is phenylephrine.   The compound or its salt which has the urination disorder preventive and therapeutic action obtained by the screening method of Claim 41. Ar ₁ is

Indicate
Ring A is (i) halogen, (ii) C _1-6 alkoxy, (iii) halogeno C _1-6 alkoxy, (iv) amino, (v) (mono or di) C _1-6 alkylamino, (vi) 1-pyrrolidinyl, (vii) piperidino, (viii) 1-piperazinyl, (ix) N-methyl-1-piperazinyl, (x) N-acetyl-1-piperazinyl, (xi) morpholino, (xii) hexamethyleneimino, (xiii) imidazolyl, (xiv) C _1-6 alkyl optionally esterified with C _1-6 alkyl, (xv) lower alkyl-carbonylamino, (xvi) lower alkylsulfonyl amino, (xvii) aminosulfonyl, (xviii) (mono or di) C _1-6 alkylaminosulfonyl, (xix) 5 to 7-membered cyclic amino - sulfonyl (xx) carbamoyl, (xxi) (mono or di) C _{1 -6} alkylcarbamoyl, (xxii) 5- to 7-membered cyclic amino-carbonyl and ( xxiii) represents a benzene ring optionally having 1 to 4 substituents selected from cyano,
R ¹ and R ^{1 ′} are each a (1) hydrogen atom, (2) a C _1-6 alkyl group optionally having one or two substituents selected from hydroxy and C _1-6 alkoxy-carbonyl, respectively. Or a C _7-16 aralkyl group or (3) Formula — (C═O) —R ^{2 ′} , — (C═O) —NR ^{2 ′} R ^{3 ′} or —SO ₂ R ^{2 ′} [wherein R ^{2 ′} And R ^{3 ′} each represent a hydrogen atom, optionally halogenated C _1-6 alkyl or C _6-10 aryl. ] Represents a group represented by
L ₁ represents a C _4-6 alkylene group optionally having 1 to 4 substituents selected from a halogen atom, nitro, cyano, optionally halogenated C _1-6 alkoxy and hydroxy;
L ₂ represents a C _2-4 alkylene group _optionally having 1 to 4 substituents selected from a halogen atom, hydroxy, oxo and phenyl;
R represents (i) a hydrogen atom, (ii) a C _1-4 alkyl group which may have 1 to 3 substituents selected from a halogen atom and hydroxy, or (iii) a C _7-16 aralkyl group,
X represents a bond, an oxygen atom or NH,
Ar ₂ is substituted with halogen, C _1-6 alkyl, halogeno C _1-6 alkyl, hydroxy, C _1-6 alkoxy, halogeno C _1-6 alkoxy, nitro, amino, cyano, carbamoyl, C _1-6 alkyl, respectively is amino optionally substituted at a carbamoyl or formyl optionally, C _1-3 alkylenedioxy, C _1-6 alkyl optionally substituted aminocarbonyl group, 5- to 7-membered cyclic amino - carbonyl Claims showing a C _6-10 aryl group _optionally having 1 to 5 substituents selected from oxy, aminosulfonyl, mono-C _1-6 alkylaminosulfonyl and di-C _1-6 alkylaminosulfonyl Item 14. The compound according to Item 14. Ring A may have 1 or 2 substituents selected from aminosulfonyl, mono- or di-C _1-6 alkylaminosulfonyl, carbamoyl and mono- or di-C _1-6 alkyl-carbamoyl. Benzene ring,
R ¹ and R ^{1 ′} are each a (1) hydrogen atom, (2) a C _1-6 alkyl group optionally having one or two substituents selected from hydroxy and C _1-6 alkoxy-carbonyl, respectively. Or a C _7-16 aralkyl group or (3) Formula — (C═O) —R ^{2 ′} , — (C═O) —NR ^{2 ′} R ^{3 ′} or —SO ₂ R ^{2 ′} [wherein R ^{2 ′} And R ^{3 ′} each represents a hydrogen atom, C _1-6 alkyl or C _6-10 aryl which may be halogenated. ] Represents a group represented by
L ₁ represents a C _4-5 alkylene group,
L ₂ represents a C _2-3 alkylene group which may have phenyl, hydroxy or oxo,
R represents a hydrogen atom or a C _1-4 alkyl group,
X represents a bond, an oxygen atom or NH,
Ar ₂ represents 1 to 3 substituents each selected from halogen, nitro, hydroxy, optionally halogenated C _1-6 alkyl, optionally halogenated C _1-6 alkoxy and aminosulfonyl. _45. The compound according to claim 44, which represents a C _6-10 aryl group which may be present. (1) 5- [5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(2) 5- [5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof ,
(3) 5- [5- [methyl (2-phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(4) 5- [5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(5) 1,3-dimethyl-5- [5- [methyl (2-phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(6) 5- [5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or its salt,
(7) 5- [5-[(2-phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(8) 5- (5-[[2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(9) 5- (5-[[2- (2-chlorophenyl) ethyl] amino] pentanoyl) -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(10) 1,3-dimethyl-5- [5-[(2-phenylethyl) amino] pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(11) 5- (5-[[2- (2-methoxyphenyl) ethyl] amino] pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(12) 1,3-dimethyl-5- [5-({2- [2- (trifluoromethoxy) phenyl] ethyl} amino) pentanoyl] -1,3-dihydro-2H-benzimidazol-2-one or Its salt,
(13) 5- (5-{[3- (2-methoxyphenyl) propyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(14) 5- (5-{[2- (2-ethoxyphenoxy) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(15) 5- [5-({2-[(2-ethoxyphenyl) amino] ethyl} amino) pentanoyl] -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or its salt,
(16) (±) -1,3-Dimethyl-5- {5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] hexanoyl} -1,3-dihydro-2H-benzimidazol-2- On or its salt,
(17) 5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(18) 5- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(19) 6- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof,
(20) 5- (5-{[2- (2-chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof ,
(21) 6- (5-{[2- (2-chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1-methyl-1,3-dihydro-2H-benzimidazol-2-one or a salt thereof Or (22) 5- (5-{[2- (2-chloro-4-hydroxyphenyl) ethyl] amino} pentanoyl) -1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2- The compound according to claim 14, which is ON or a salt thereof. (1) 5-{[2- (2-chlorophenyl) ethyl] amino} -1- (2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -1- Pentanone or a salt thereof,
(2) 5-{[2- (2-chlorophenyl) ethyl] amino} -1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazole-5 -Yl) -1-pentanone or a salt thereof,
(3) 5-[[2- (2-Chlorophenyl) ethyl] (methyl) amino] -1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzo Thiadiazol-5-yl) -1-pentanone or a salt thereof,
(4) 1- (1,3-Dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazol-5-yl) -5-[[2- (2-methoxyphenyl) Ethyl] (methyl) amino] -1-pentanone or a salt thereof, or (5) 1- (1,3-dimethyl-2,2-dioxide-1,3-dihydro-2,1,3-benzothiadiazole-5 15. The compound according to claim 14, which is -yl) -5- (5-methoxy-3,4-dihydro-2 (1H) -isoquinolinyl) -1-pentanone or a salt thereof. (1) 6- {5-[(2-phenylethyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone or a salt thereof,
(2) 6- (5-{[2- (2-methoxyphenyl) ethyl] amino} pentanoyl) -3,4-dihydro-2 (1H) -quinazolinone or a salt thereof,
(3) 6- (5-{[2- (2-chlorophenyl) ethyl] amino} pentanoyl) -3,4-dihydro-2 (1H) -quinazolinone or a salt thereof,
(4) 6- {5- [methyl (2-phenylethyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone or a salt thereof,
(5) 6- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone or a salt thereof,
(6) 6- {5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone or a salt thereof,
(7) 1,3-dimethyl-6- {5- [methyl (2-phenylethyl) amino] pentanoyl} -3,4-dihydro-2 (1H) -quinazolinone or a salt thereof,
(8) 6- {5-[[2- (2-methoxyphenyl) ethyl] (methyl) amino] pentanoyl} -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone or a salt thereof, Or (9) 6- {5-[[2- (2-chlorophenyl) ethyl] (methyl) amino] pentanoyl} -1,3-dimethyl-3,4-dihydro-2 (1H) -quinazolinone or a salt thereof 15. A compound according to claim 14.