JPH03145471A - Production of 1,2,3,4-tetrahydroacridine compound - Google Patents
Production of 1,2,3,4-tetrahydroacridine compoundInfo
- Publication number
- JPH03145471A JPH03145471A JP28177589A JP28177589A JPH03145471A JP H03145471 A JPH03145471 A JP H03145471A JP 28177589 A JP28177589 A JP 28177589A JP 28177589 A JP28177589 A JP 28177589A JP H03145471 A JPH03145471 A JP H03145471A
- Authority
- JP
- Japan
- Prior art keywords
- acridine
- compound
- tetrahydroacridine
- hydrogenation
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- RXBYRTSOWREATF-UHFFFAOYSA-N tetrahydroacridine Natural products C1=CC=C2C=C(CCCC3)C3=NC2=C1 RXBYRTSOWREATF-UHFFFAOYSA-N 0.000 title claims abstract description 7
- -1 1,2,3,4-tetrahydroacridine compound Chemical class 0.000 title claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 23
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims abstract description 19
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims abstract description 7
- XJGFWWJLMVZSIG-UHFFFAOYSA-N 9-aminoacridine Chemical compound C1=CC=C2C(N)=C(C=CC=C3)C3=NC2=C1 XJGFWWJLMVZSIG-UHFFFAOYSA-N 0.000 claims description 11
- 229960001441 aminoacridine Drugs 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 abstract description 13
- 238000005984 hydrogenation reaction Methods 0.000 abstract description 10
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 5
- 125000003277 amino group Chemical group 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 229910052697 platinum Inorganic materials 0.000 abstract description 3
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 2
- 238000005576 amination reaction Methods 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 150000001204 N-oxides Chemical class 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 3
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 3
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 2
- BPXINCHFOLVVSG-UHFFFAOYSA-N 9-chloroacridine Chemical compound C1=CC=C2C(Cl)=C(C=CC=C3)C3=NC2=C1 BPXINCHFOLVVSG-UHFFFAOYSA-N 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 235000012501 ammonium carbonate Nutrition 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- IXTPCSZJZAKJTO-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7,8,8a,9,9a,10,10a-tetradecahydroacridine Chemical compound N1C2CCCCC2CC2C1CCCC2 IXTPCSZJZAKJTO-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- FTGPOQQGJVJDCT-UHFFFAOYSA-N 9-aminoacridine hydrochloride Chemical class Cl.C1=CC=C2C(N)=C(C=CC=C3)C3=NC2=C1 FTGPOQQGJVJDCT-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FZEYVTFCMJSGMP-UHFFFAOYSA-N acridone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3NC2=C1 FZEYVTFCMJSGMP-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Landscapes
- Other In-Based Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は１．２．３．４−テトラヒドロアクリジン化合
物の製造方法に関する。このような化合物はアルツハイ
マー型老人性痴呆薬あるいはその中間体等として有用で
ある。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing a 1.2.3.4-tetrahydroacridine compound. Such compounds are useful as Alzheimer's type senile dementia drugs or intermediates thereof.
アクリジンを白金族系触媒の存在下で水素化することは
、特開昭６３−７７、８６０号公報等で公知であり、１
．２．３．４．５．６．７．８−オクタヒドロアクリジ
ン、１、２．３．４．４ａ、 ９．９ａ、 １０−オク
タヒドロアクリジン又はパーヒドロアクリジンを選択的
に製造することができる。しかしながら、１．２．３．
４−テトラヒドロアクリジンを選択的に製造することは
困難である。Hydrogenation of acridine in the presence of a platinum group catalyst is known from JP-A No. 63-77, No. 860, etc., and 1
．． 2.3.4.5.6.7.8-octahydroacridine, 1, 2.3.4.4a, 9.9a, 10-octahydroacridine or perhydroacridine can be selectively produced . However, 1.2.3.
It is difficult to selectively produce 4-tetrahydroacridine.
９−アミノ−１，２，３，４−テトラヒドロアクリジン
等の１．２．３．４−テトラヒドロアクリジン化合物は
古くから医薬品又はその中間体として有用であることが
知られており、種々の合成法が研究されてきた（例えば
、Ｊ、 Ｃｈｅｍ、 Ｓａｃ、、 １９４７．６３４、
Ｔｅｔｒａｈｅｄｒｏｎ Ｌｅｔｔ、、 Ｎｏ、２０．
１２７７（１９６３）、ｔｌｓｓＲ特許第３１９゜５９
６号等）。そして、これらの研究例で明らかなように、
このような化合物の合成法としては閉環反応でテトラヒ
ドロアクリジン環を合成する方法がもっばらであった。1,2,3,4-tetrahydroacridine compounds such as 9-amino-1,2,3,4-tetrahydroacridine have long been known to be useful as pharmaceuticals or intermediates thereof, and can be synthesized using various synthetic methods. have been studied (e.g., J. Chem. Sac, 1947.634,
Tetrahedron Lett, No. 20.
1277 (1963), tlssR Patent No. 319°59
No. 6, etc.). And, as is clear from these research examples,
The most common method for synthesizing such compounds has been to synthesize a tetrahydroacridine ring through a ring-closing reaction.
コールタール中などに含まれており、安価に得ることが
できるアクリジンを原料として１．２．３．４テトラヒ
ドロアクリジン化合物を経済的、かつ効率よく合成する
ことができれば、工業的に極めて望ましいことといえる
。本発明はこのような合成法を提供することを目的とす
る。It would be extremely desirable industrially if 1.2.3.4 tetrahydroacridine compounds could be synthesized economically and efficiently using acridine, which is contained in coal tar and can be obtained at low cost, as a raw material. I can say that. The present invention aims to provide such a synthetic method.
本発明者らは、上記のような課題を解決するため鋭意研
究を行い、９−アミノアクリジンを水素化すると選択的
に１．２．３．４−テトラヒドロアクリジン化合物が得
られることを見出し、本発明を完成した。The present inventors conducted extensive research to solve the above problems and discovered that 1.2.3.4-tetrahydroacridine compound can be selectively obtained by hydrogenating 9-aminoacridine. Completed the invention.
すなわち、本発明は、アクリジンの９−位をアミン化し
たのち、水素化することを特徴とするｌ、２゜３．４−
テトラヒドロアクリジン化合物の製造方法および９−ア
ミノアクリジン又はその塩を、白金族系触媒の存在下に
水素ガスと反応させることを特徴とする１、 ２．３．
４−テトラヒドロアクリジン化合物の製造方法である。That is, the present invention is characterized in that the 9-position of acridine is aminated and then hydrogenated.
1, 2.3. A method for producing a tetrahydroacridine compound, characterized by reacting 9-aminoacridine or a salt thereof with hydrogen gas in the presence of a platinum group catalyst.
This is a method for producing a 4-tetrahydroacridine compound.
請求項１に記載した発明において、アクリジンの９−位
をアミノ化する方法としては、アクリジンを過安息香酸
で酸化してＮ−オキシドとし、次いで無水酢酸中でリフ
ラックスして９−アクリダノンとし、これを塩化チオニ
ル、オキシ塩化リン、五塩化リン等の塩素化剤と反応さ
せる方法、あるいはＮ−オキシドに五塩化リンを反応さ
せるような方法で塩素化し、得られた９−クロロアクリ
ジンを炭酸アンモニウムとをフェノールの存在下、１２
０８Ｃ前後の温度で反応させて９−アミノアクリジンと
する等の方法がある（Ｏｒｇ、 ５ｙｎｔｈ、 Ｃｏ１
１． Ｖｏｌ、 １９５５、 ＩＩＩ、 ５３）。In the invention described in claim 1, the method for aminating the 9-position of acridine includes oxidizing acridine with perbenzoic acid to form an N-oxide, then refluxing it in acetic anhydride to form 9-acridanone, This is chlorinated by a method of reacting with a chlorinating agent such as thionyl chloride, phosphorus oxychloride, or phosphorus pentachloride, or by a method of reacting phosphorus pentachloride with N-oxide, and the resulting 9-chloroacridine is treated with ammonium carbonate. and in the presence of phenol, 12
There are methods such as reacting at a temperature around 08C to form 9-aminoacridine (Org, 5ynth, Co1
1. Vol. 1955, III, 53).
９−アミノアクリジンの水素化は、水素化触媒の存在下
、水素ガスと反応させることにより行う。Hydrogenation of 9-aminoacridine is performed by reacting it with hydrogen gas in the presence of a hydrogenation catalyst.
この反応においては、アミノ基によってアクリジンの、
中央の環の水素化が阻害され、１．２．３．４−位が選
択的に水素化される。したがって、請求項１の発明では
触媒の種類、反応条件等は任意であるが、水素化触媒と
して白金族系触媒を使用すればより選択性が向上する。In this reaction, acridine is
Hydrogenation of the central ring is inhibited and the 1,2,3,4-positions are selectively hydrogenated. Therefore, in the invention of claim 1, the type of catalyst, reaction conditions, etc. are arbitrary, but if a platinum group catalyst is used as the hydrogenation catalyst, the selectivity will be further improved.
また、９−アミノアクリジンは、塩酸塩、硫酸塩のよう
な塩の形で用いてもよいが、収量がやや低い。Furthermore, 9-aminoacridine may be used in the form of a salt such as hydrochloride or sulfate, but the yield is rather low.
請求項２の発明では、水素化触媒として白金族系触媒を
使用する。白金族系触媒としては白金、パラジウム、ル
テニウム等の白金族金属をアルミナ、カーボン等の担体
に担持させた触媒が挙げられる。この場合の白金族金属
の担持量は０．１〜ＩＯ重量％の範囲が好ましい。また
、白金族金属としてパラジウム触媒を用いると、最もよ
い収量を与える。水素化触媒の使用量はバッチ反応で、
３〜５重量％の白金族金属を担持した触媒を用いる場合
、原料の９−アミノアクリジンに対し０． １〜２．５
重態％程度である。In the invention of claim 2, a platinum group catalyst is used as the hydrogenation catalyst. Examples of platinum group catalysts include catalysts in which platinum group metals such as platinum, palladium, and ruthenium are supported on carriers such as alumina and carbon. In this case, the amount of platinum group metal supported is preferably in the range of 0.1 to IO weight %. Also, the use of a palladium catalyst as the platinum group metal gives the best yield. The amount of hydrogenation catalyst used is for batch reaction.
When using a catalyst supporting 3 to 5% by weight of a platinum group metal, 0.0% to 9-aminoacridine as a raw material is used. 1-2.5
He is in a serious condition.
反応は７０〜１２０°Ｃ１水素圧力２０ ｋｇ／ ｃｒ
ｌ、Ｇ以上の条件で行うことが好ましい。１２０℃を越
える高温又は１００ ｋｇ／ｃｒｉ、Ｇ以上の高い水素
圧力の条件では、反応率が高く、反応時間も短縮される
が、パーヒドロ化が起こりやすくなり、選択率が低下す
る。したがって、より好ましくは反応温度８０〜１００
℃、水素圧力５０〜８０ ｋｇ／ｃｎｆ、Ｇである。反
応は、原料の９−アミノアクリジンを適当な溶媒に溶解
し、触媒を加え、水素ガス加圧下に攪拌しながら反応さ
せる方法等を挙げることができる。The reaction is 70-120°C1 hydrogen pressure 20 kg/cr
It is preferable to carry out the test under conditions of 1, G or higher. At a high temperature exceeding 120° C. or a high hydrogen pressure of 100 kg/cri, G or higher, the reaction rate is high and the reaction time is shortened, but perhydration tends to occur and the selectivity decreases. Therefore, the reaction temperature is more preferably 80 to 100.
℃, hydrogen pressure 50-80 kg/cnf, G. The reaction may be carried out by dissolving 9-aminoacridine as a raw material in a suitable solvent, adding a catalyst, and reacting with stirring under pressure of hydrogen gas.
本発明の１．２．３．４−テトラヒドロアクリジン化合
物は、９−アミノ−１，２，３，４−テトラヒドロアク
リジン自体、およびこの誘導体であり、誘導体してはア
ミノ基を除去又はアミン基と反応しうる化合物を反応さ
せて得られる化合物、アクリジン骨格に置換基を結合さ
せた化合物などがある。The 1.2.3.4-tetrahydroacridine compound of the present invention is 9-amino-1,2,3,4-tetrahydroacridine itself and its derivatives, and the derivatives include removing the amino group or adding an amine group. These include compounds obtained by reacting reactive compounds, and compounds in which a substituent is bonded to an acridine skeleton.
実施例１
アクリジンを、クロロホルム中、過安息香酸で酸化して
Ｎ−オキシドとし、次いで五塩化リン反応させて９−ク
ロロアクリジンとした。これに炭酸アンモニウムを加え
て、フェノールの存在下、１２０°Ｃ１４５分間攪拌し
て９−アミノアクリジンを得た。Example 1 Acridine was oxidized with perbenzoic acid in chloroform to give the N-oxide, and then reacted with phosphorus pentachloride to give 9-chloroacridine. Ammonium carbonate was added to this, and the mixture was stirred at 120°C for 145 minutes in the presence of phenol to obtain 9-aminoacridine.
この９−アミノアクリジンの塩酸塩１ｇ、触媒０゜２５
ｇおよび溶媒としてのエタノールｌｏｇを、内容積５０
−の電磁攪拌式のオートクレーブに入れ、水素ガスを封
入後、１００℃で１０分間反応を行った。1 g of this 9-aminoacridine hydrochloride, 0°25 catalyst
g and ethanol log as solvent, internal volume 50
- The autoclave was placed in a magnetic stirring type autoclave, and after hydrogen gas was sealed, a reaction was carried out at 100°C for 10 minutes.
反応終了後、生成物を取り出し、ベンゼンに溶解させ、
このベンゼン溶液を水酸化ナトリウムの希薄溶液で洗浄
し、無水硫酸ナトリウムで脱水したのち、ガスクロマト
グラフで分析した。また、目的生成物である９−アミノ
−１，２，３，４−テトラヒドロアクリジンは、’Ｈ−
Ｎ Ｍ Ｒおよび” Ｃ−Ｎ Ｍ Ｒ並びにＧＣ−ＭＳ
で確認した。その他の条件および９−アミノ−１，２，
３，４−テトラヒドロアクリジンの選択率、収率を第１
表に示す。After the reaction is complete, the product is taken out and dissolved in benzene.
This benzene solution was washed with a dilute solution of sodium hydroxide, dehydrated with anhydrous sodium sulfate, and then analyzed by gas chromatography. In addition, the target product 9-amino-1,2,3,4-tetrahydroacridine is 'H-
NMR and "C-NMR and GC-MS
I confirmed it. Other conditions and 9-amino-1,2,
The selectivity and yield of 3,4-tetrahydroacridine were
Shown in the table.
第 １ 表
実施例２
９−アミノアクリジン５ｇ、白金属金属をアルミナ又は
カーボンに５％担持させた触媒０．５ｇおよびエタノー
ル１００ｄを、内容積３００ｄの電磁攪拌式オートクレ
ーブに入れ、水素圧６０ｋｇ／ｃｒｔ、Ｇ、 ８０℃で
２時間反応を行った。Table 1 Example 2 5 g of 9-aminoacridine, 0.5 g of a catalyst with 5% platinum metal supported on alumina or carbon, and 100 d of ethanol were placed in a magnetic stirring autoclave with an internal volume of 300 d, and the hydrogen pressure was 60 kg/cr. , G. The reaction was carried out at 80°C for 2 hours.
反応終了後、内容物を濾過して、触媒を除去したのち、
エタノールを蒸留除去して得られた固形物を常法に従っ
てカラムクロマトグラフで精製した。結果を第２表に示
す。After the reaction is complete, the contents are filtered to remove the catalyst.
The solid material obtained by distilling off the ethanol was purified by column chromatography according to a conventional method. The results are shown in Table 2.
第 ２ 表
（注）■Ｐｄ／Ａ、 Ｒｈ／Ａ１ｐｔ／Ａは、それぞれ
Ｐｄ、 Ｒｈ。Table 2 (Note) ■Pd/A and Rh/A1pt/A are Pd and Rh, respectively.
Ｐｔをアルミナに５％担持させた触媒である。This is a catalyst in which 5% of Pt is supported on alumina.
■Ｐｄ／Ｃは、カーボンにＰｄを５％担持させた触媒で
ある。(2) Pd/C is a catalyst in which 5% of Pd is supported on carbon.
（注）記号、単位は第１表と同じ。(Note) Symbols and units are the same as in Table 1.
実施例３
９−アミノアクリジン１００ｇ、３％Ｐｄ／アルミナ触
媒１５ｇおよびエタノール５００ｍ１をオートクレーブ
に入れ、水素ガスを封入したのち、反応を行った。条件
および結果を第３表に示す。Example 3 100 g of 9-aminoacridine, 15 g of 3% Pd/alumina catalyst, and 500 ml of ethanol were placed in an autoclave, and hydrogen gas was sealed therein, followed by a reaction. The conditions and results are shown in Table 3.
第 ３ 表
〔発明の効果〕
本発明方法によれば、アクリジン環の１．２．３．４−
位を選択的に水素化することができ、有利に１，２゜３
．４−テトラヒドロアクリジン化合物を収率良く製造す
ることができる。Table 3 [Effects of the Invention] According to the method of the present invention, 1.2.3.4- of the acridine ring
It is possible to selectively hydrogenate the 1,2°3
．． A 4-tetrahydroacridine compound can be produced with good yield.
Claims (2)
することを特徴とする１，２，３，４−テトラヒドロア
クリジン化合物の製造方法。(1) A method for producing a 1,2,3,4-tetrahydroacridine compound, which comprises aminating the 9-position of acridine and then hydrogenating it.
媒の存在下に水素ガスと反応させることを特徴とする１
，２，３，４−テトラヒドロアクリジン化合物の製造方
法。(2) 1 characterized in that 9-aminoacridine or its salt is reacted with hydrogen gas in the presence of a platinum group catalyst.
, 2,3,4-Tetrahydroacridine compound manufacturing method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28177589A JPH03145471A (en) | 1989-10-31 | 1989-10-31 | Production of 1,2,3,4-tetrahydroacridine compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP28177589A JPH03145471A (en) | 1989-10-31 | 1989-10-31 | Production of 1,2,3,4-tetrahydroacridine compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03145471A true JPH03145471A (en) | 1991-06-20 |
Family
ID=17643806
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP28177589A Pending JPH03145471A (en) | 1989-10-31 | 1989-10-31 | Production of 1,2,3,4-tetrahydroacridine compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03145471A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114130389A (en) * | 2021-08-31 | 2022-03-04 | 浙江工业大学 | Supported catalyst, preparation thereof and application thereof in selective hydrogenation of nitrogen-containing heterocyclic compound |
-
1989
- 1989-10-31 JP JP28177589A patent/JPH03145471A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114130389A (en) * | 2021-08-31 | 2022-03-04 | 浙江工业大学 | Supported catalyst, preparation thereof and application thereof in selective hydrogenation of nitrogen-containing heterocyclic compound |
| CN114130389B (en) * | 2021-08-31 | 2023-11-17 | 浙江工业大学 | Supported catalyst, preparation thereof and application thereof in selective hydrogenation of nitrogen-containing heterocyclic compound |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS61238777A (en) | Manufacture of tetraalkyl-piperidyl-amine | |
| CN108440330B (en) | Preparation method of doxycycline hydrochloride | |
| EP1939178B1 (en) | Process for producing 1-benzyl-4-[(5,6-dimethoxy-1indanon)-2-yl]methylpiperidine or hydrochloride thereof | |
| US7795438B2 (en) | Processes for producing 1-benzyl-4-[(5,6-dimethoxy-1indanon)-2-yl]methylpiperidine and hydrochloride | |
| WO2005044805A1 (en) | A novel process for preparing donepezil and its derivatives | |
| CN1434800A (en) | Pyridine-1-oxide derivative, and process for its transformation into pharmaceutically effective compunds | |
| JPH0212958B2 (en) | ||
| KR20220051168A (en) | Method for preparing heterocyclideneacetamide derivatives | |
| BR112021014815A2 (en) | METHOD FOR PREPARATION OF 4-AMINO-5-METHYLPYRIDONE | |
| JPH03145471A (en) | Production of 1,2,3,4-tetrahydroacridine compound | |
| JPH01193246A (en) | Production of 2,3-dichloropyridine | |
| JP2912572B2 (en) | Method for producing optically active amines | |
| CN108602758B (en) | Process for preparing trans-4-amino-1-cyclohexanecarboxylic acids and derivatives thereof | |
| CN110002930B (en) | Method for hydrogenation reduction of alkenyl aromatic halogenated derivatives | |
| CN116041220B (en) | Preparation method of aryl substituted amide compound | |
| KR101479986B1 (en) | New process for the synthesis of ivabradine and addition salts thereof with a pharmaceutically acceptable acid | |
| JPH0586393B2 (en) | ||
| CN112679431B (en) | Method for preparing isoquinolinones compound | |
| JPH10279552A (en) | 7-(n-substituted amino)-2-phenylheptanoic acid ester derivative and production of the derivative | |
| CN107445879B (en) | Preparation method of Latricinib intermediate | |
| CN109305932B (en) | Preparation method of silodosin intermediate | |
| FI92586C (en) | New stereoselective hydrogenation process | |
| CN117986189A (en) | Preparation method of spiro compound | |
| JPH03176463A (en) | Pyrrolidinol derivative and its production | |
| JP2003342259A (en) | Method for producing optically active cis-piperidine derivative |