JPH0447666B2 - - Google Patents
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- Publication number
- JPH0447666B2 JPH0447666B2 JP3125884A JP3125884A JPH0447666B2 JP H0447666 B2 JPH0447666 B2 JP H0447666B2 JP 3125884 A JP3125884 A JP 3125884A JP 3125884 A JP3125884 A JP 3125884A JP H0447666 B2 JPH0447666 B2 JP H0447666B2
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- formula
- compound
- bonded
- ethyl
- 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.)
- Expired
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- 125000000168 pyrrolyl group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- -1 acetoxyacetyl halide Chemical class 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 10
- 238000000862 absorption spectrum Methods 0.000 description 9
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 9
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 150000003233 pyrroles Chemical class 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- PVJJEAZZAOUWNR-UHFFFAOYSA-N 3-[2-(1h-pyrrol-2-yl)ethyl]-1,3-oxazolidine-2,4-dione Chemical compound O=C1COC(=O)N1CCC1=CC=CN1 PVJJEAZZAOUWNR-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 208000007107 Stomach Ulcer Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 208000000718 duodenal ulcer Diseases 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- HZDNNJABYXNPPV-UHFFFAOYSA-N (2-chloro-2-oxoethyl) acetate Chemical compound CC(=O)OCC(Cl)=O HZDNNJABYXNPPV-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- IAZZNTYMXXEHHT-UHFFFAOYSA-N 2-(1h-pyrrol-2-yl)ethanamine Chemical compound NCCC1=CC=CN1 IAZZNTYMXXEHHT-UHFFFAOYSA-N 0.000 description 2
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- RIEVLFARERLSRN-UHFFFAOYSA-N O=C1CCC(=O)N1CCC1=CC=CN1 Chemical compound O=C1CCC(=O)N1CCC1=CC=CN1 RIEVLFARERLSRN-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940014800 succinic anhydride Drugs 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical compound O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 229960000380 propiolactone Drugs 0.000 description 1
- ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical compound O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Landscapes
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
【発明の詳細な説明】
本発明は新規なピロール誘導体に関するもので
ある。更に詳しく述べれば、本発明は、抗かいよ
う作用を有し、人間を含む哺乳動物の胃、十二指
腸かいように対する治療及び予防用医薬品として
有用な、一般式
（式中のＡは炭素数１〜４のアルキレン、Ｂは酸
素原子、ｌ及びｎのいずれか一方は１、他の一方
は０又は１、ｍは１〜３の整数、但し、ｌ、ｍ及
びｎの総和が３又は４であり、Ａはピロール環の
２位又は３位に結合するものである）で表わされ
る新規なピロール誘導体に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel pyrrole derivatives. More specifically, the present invention provides a general formula that has an anti-inflammatory effect and is useful as a pharmaceutical for the treatment and prevention of gastric and duodenal ulcers in mammals including humans. (In the formula, A is alkylene having 1 to 4 carbon atoms, B is an oxygen atom, one of l and n is 1, the other is 0 or 1, m is an integer of 1 to 3, provided that l, m and the sum of n is 3 or 4, and A is bonded to the 2- or 3-position of the pyrrole ring.
本発明のピロール誘導体は文献未記載の新規な
化合物であり、各種実験動物を用いた実験的かい
ようの発現に対して顕著な抑制効果を示す。従つ
て、本発明の前記一般式(1)のピロール誘導体は人
間を含む哺乳動物の胃、十二指腸かいように対す
る治療及び予防用医薬品として有用である。 The pyrrole derivative of the present invention is a novel compound that has not been described in any literature, and exhibits a remarkable suppressive effect on the development of experimental ulcers using various experimental animals. Therefore, the pyrrole derivative of the general formula (1) of the present invention is useful as a therapeutic and preventive drug for gastric and duodenal ulcers in mammals including humans.
本発明の目的は、このように医薬品として有用
な、新規なピロール誘導体を提供することであ
る。 An object of the present invention is thus to provide novel pyrrole derivatives useful as pharmaceuticals.
本発明の一般式(1)の化合物はいくつかの方法に
よつて製造される。例えば、一般式(1)の化合物
で、ｌ及びｎが共に１、ｍが１又は２である、一
般式
（式中のＡは前記と同じ意味をもち、しかもピロ
ール環の２位又は３位に結合するものであり、
m′は１又は２である）で表わされる化合物は、
一般式
（式中のＡ及びm′は前記と同じ意味をもち、Ａ
はピロール環の２位又は３位に結合するものであ
る）で表わされる化合物に、Ｎ，N′−カルボニ
ルジイミダゾールなどのようなカルボニル化合物
を反応させるか、あるいは前記一般式(2)の化合物
にクロル炭酸メチル、クロル炭酸エチルなどのよ
うなハロ炭酸エステル誘導体を反応させて、一般
式
（式中のＡ及びm′は前記と同じ意味をもち、Ａ
はピロール環の２位又は３位に結合するものであ
り、Ｒは炭素数１〜３のアルキル基である）で表
わされる化合物を製し、これをナトリウムメトキ
シドなどのような塩基性物質の存在下に加熱する
ことなどによつて製造することができる。 The compounds of general formula (1) of the present invention can be produced by several methods. For example, a compound of general formula (1), where l and n are both 1 and m is 1 or 2, (A in the formula has the same meaning as above, and is bonded to the 2- or 3-position of the pyrrole ring,
m' is 1 or 2),
general formula (A and m' in the formula have the same meanings as above,
is bonded to the 2- or 3-position of the pyrrole ring) with a carbonyl compound such as N,N'-carbonyldiimidazole, or the compound of the general formula (2) By reacting halocarbonate derivatives such as methyl chlorocarbonate, ethyl chlorocarbonate, etc., the general formula (A and m' in the formula have the same meanings as above,
is bonded to the 2- or 3-position of the pyrrole ring, and R is an alkyl group having 1 to 3 carbon atoms. It can be produced by, for example, heating in the presence of
この製造方法において出発原料として用いられ
る一般式(2)の化合物は、一般式
（式中のＡは前記と同じ意味をもち、しかもピロ
ール環の２位又は３位に結合するものである）で
表わされるアミノアルキルピロールにアセトキシ
アセチルクロリドのようなアセトキシアセチルハ
ライドを反応させて、一般式
（式中のＡは前記と同じ意味をもち、しかもピロ
ール環の２位又は３位に結合するものである）で
表わされる化合物を製し、次いでこれを常法によ
り加水分解するか、又は一般式(4)の化合物にβ−
プロピオラクトンを反応させることによつて容易
に製造される。 The compound of general formula (2) used as a starting material in this production method has the general formula (A in the formula has the same meaning as above and is bonded to the 2- or 3-position of the pyrrole ring) is reacted with an acetoxyacetyl halide such as acetoxyacetyl chloride, general formula (A in the formula has the same meaning as above and is bonded to the 2- or 3-position of the pyrrole ring) is prepared and then hydrolyzed by a conventional method, or β- to the compound of formula (4)
It is easily produced by reacting propiolactone.
本発明の前記一般式(1)の化合物で、ｌが０、ｍ
が２又は３、ｎが１である、一般式
（式中のＡは前記と同じ意味をもち、Ａはピロー
ル環の２位又は３位に結合するものであり、
m″は２又は３である）で表わされる化合物は、
一般式
（式中のＡ及びm″は前記と同じ意味をもち、Ａ
はピロール環の２位又は３位に結合するものであ
る）で表わされる化合物で、Ｎ，N′−カルボニ
ルジイミダゾールなどのようなカルボニル化合物
を反応させるか、あるいは前記一般式(6)の化合物
にクロル炭酸メチル、クロル炭酸エチルなどのよ
うなハロ炭酸エステル誘導体を反応させて、一般
式
（式中のＡ、m″及びＲは前記と同じ意味をもち、
Ａはピロール環の２位又は３位に結合するもので
ある）で表わされる化合物を製し、これをナトリ
ウムメトキシドなどのような塩基性物質の存在下
に加熱することなどによつて製造することができ
る。 In the compound of the above general formula (1) of the present invention, l is 0, m
is 2 or 3, n is 1, the general formula (A in the formula has the same meaning as above, A is bonded to the 2- or 3-position of the pyrrole ring,
m″ is 2 or 3),
general formula (A and m″ in the formula have the same meanings as above,
is bonded to the 2- or 3-position of the pyrrole ring), and can be reacted with a carbonyl compound such as N,N'-carbonyldiimidazole, or a compound of the general formula (6) above. By reacting halocarbonate derivatives such as methyl chlorocarbonate, ethyl chlorocarbonate, etc., the general formula (A, m'' and R in the formula have the same meanings as above,
A is bonded to the 2- or 3-position of the pyrrole ring) and heating it in the presence of a basic substance such as sodium methoxide. be able to.
この製造方法において出発原料として用いられ
る一般式(6)の化合物は、前記一般式(2)の化合物を
適当な還元剤で還元するか、あるいは一般式
（式中のCHOはピロール環の２位又は３位に結
合するものである）で表わされるピロールカルバ
ルデヒドに、一般式
H2N−（CH2）n″−OH (9)
（式中のm″は前記と同じ意味をもつ）で表わさ
れる２−アミノエタノールまたは３−アミノ−１
−プロパノールのようなアミノアルコール類を反
応させて、一般式
（式中のm″は前記と同じ意味をもち、Ａはピロ
ール環の２位又は３位に結合するものである）で
表わされるシツフ塩基を製し、これを適当な還元
剤で還元することによつて容易に製造される。 The compound of general formula (6) used as a starting material in this production method can be obtained by reducing the compound of general formula (2) with an appropriate reducing agent or by reducing the compound of general formula (2) with a suitable reducing agent or (CHO in the formula is bonded to the 2- or 3-position of the pyrrole ring) is combined with the general formula H 2 N-(CH 2 ) n ″-OH (9) (in the formula 2-aminoethanol or 3-amino-1 (m″ has the same meaning as above)
-By reacting amino alcohols such as propanol, the general formula (In the formula, m'' has the same meaning as above, and A is bonded to the 2- or 3-position of the pyrrole ring.) Preparing a Schiff base and reducing it with an appropriate reducing agent. easily manufactured by
本発明の前記一般式(1)の化合物で、ｌが１、ｍ
が２又は３、ｎが０である、一般式
（式中のＡ及びm″は前記と同じ意味をもち、Ａ
はピロール環の２位又は３位の結合する物であ
る）で表わされる化合物は、一般式(4)の化合物
に、一般式
（式中のm″は前記と同じ意味をもつ）で表わさ
れる無水コハク酸または無水グルタル酸のような
環状酸無水物を反応させて、一般式
（式中のＡ及びm″は前記と同じ意味をもち、Ａ
はピロール環の２位又は３位に結合するものであ
る）で表わされる化合物を製し、これを加熱して
閉環させることにより製造することができる。こ
の場合、一般式(4)の化合物と一般式（11）の化合
物とを加熱下に反応させて、一般式（12）の化合
物を取り出すことなく一工程で製造することもで
きる。 In the compound of the above general formula (1) of the present invention, l is 1, m
is 2 or 3, n is 0, the general formula (A and m″ in the formula have the same meanings as above,
is a compound bonded to the 2- or 3-position of the pyrrole ring), the compound represented by the general formula (4) has the general formula (m'' in the formula has the same meaning as above) is reacted with a cyclic acid anhydride such as succinic anhydride or glutaric anhydride, and the general formula (A and m″ in the formula have the same meanings as above,
is bonded to the 2- or 3-position of the pyrrole ring) and heating the compound to cause ring closure. In this case, the compound of general formula (4) and the compound of general formula (11) can be reacted under heating to produce the compound of general formula (12) in one step without taking it out.
このようにして製造される本発明の一般式(1)の
ピロール誘導体としては、例えば３−〔２−（２−
ピロリル）エチル〕−２，４−オキサゾリジンジ
オン、３−（２−ピロリルメチル）テトラヒドロ
−2H−１，３−オキサジン−２−オン、Ｎ−〔２
−（２−ピロリル）エチル〕スクシンイミドなど
をあげることができる。 As the pyrrole derivative of the general formula (1) of the present invention produced in this way, for example, 3-[2-(2-
pyrrolyl)ethyl]-2,4-oxazolidinedione, 3-(2-pyrrolylmethyl)tetrahydro-2H-1,3-oxazin-2-one, N-[2
-(2-pyrrolyl)ethyl]succinimide and the like.
本発明の一般式(1)のピロール誘導体の抗かいよ
う作用は、各種実験動物を用いた実験的かいよう
の発現に対する抑制効果で確認される。例えば、
アスピリン負荷幽門結さつラツトでの実験におい
て、本発明の一般式(1)のピロール誘導体は、体重
Kgあたり投与量数十mgないし百数十mg程度で良好
な抑制効果を発現し、３−〔２−（２−ピロリル）
エチル〕−２，４−オキサゾリジンジオンは62
mg／Kgの投与量で50％の抑制効果を示す。 The anti-inflammatory action of the pyrrole derivative of general formula (1) of the present invention is confirmed by its inhibitory effect on the expression of experimental ulcers using various experimental animals. for example,
In experiments using aspirin-loaded pylorus-ligated rats, the pyrrole derivative of general formula (1) of the present invention
A good inhibitory effect is expressed at doses ranging from several tens of mg to over 100 mg per kg, and 3-[2-(2-pyrrolyl)
Ethyl]-2,4-oxazolidinedione is 62
It shows a 50% inhibitory effect at a dose of mg/Kg.
このように本発明の一般式(1)のピロール誘導体
強い抗かいよう作用を有し、人間を含む哺乳動物
の胃、十二指腸かいように対する治療及び予防用
医薬品として有用である。 As described above, the pyrrole derivative of the general formula (1) of the present invention has a strong anti-inflammatory effect and is useful as a pharmaceutical for the treatment and prevention of gastric and duodenal ulcers in mammals including humans.
本発明の内容を以下の実施例によつて更に詳細
に説明する。なお、各実施例における化合物の融
点はすべ未補正である。 The content of the present invention will be explained in more detail with reference to the following examples. Note that all melting points of compounds in each example are uncorrected.
実施例 １
２−（２−アミノエチル）ピロール6.7ｇとトリ
エチルアミン9.1ｇをベンゼン70mlに溶かし、氷
冷下にかき混ぜながら、アセトキシアセチルクロ
リド8.3ｇを無水ベンゼン10mlに溶かした液を滴
下したのち、室温で１時間反応させた。反応液を
減圧下に濃縮し、残留物に食塩水を加えたのち、
塩化メチレンで抽出し、無水硫酸マグネシウムで
乾燥した。減圧下に溶媒を留去し、油状物として
２−アセトキシ−Ｎ−〔２−（２−ピロリル）エチ
ル〕アセトアミド10.8ｇを得た。Example 1 6.7 g of 2-(2-aminoethyl)pyrrole and 9.1 g of triethylamine were dissolved in 70 ml of benzene, and while stirring under ice cooling, a solution of 8.3 g of acetoxyacetyl chloride dissolved in 10 ml of anhydrous benzene was added dropwise, and the mixture was cooled to room temperature. The reaction was carried out for 1 hour. After concentrating the reaction solution under reduced pressure and adding brine to the residue,
It was extracted with methylene chloride and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 10.8 g of 2-acetoxy-N-[2-(2-pyrrolyl)ethyl]acetamide as an oil.
赤外線吸収スペクトル（液膜）
3300cm-1，1740cm-1，1660cm-1
核磁気共鳴スペクトル（90MHz，CDCl3）
δ：2.02（ｓ，3H），2.74（ｔ，2H），
3.42（ｑ，2H），4.43（ｓ，2H），
5.75〜6.8（ｍ，4H），8.93（br.s，1H）
２−アセトキシ−Ｎ−〔２−（２−ピロリル）エ
チル〕アセトアミド10.7Kgを2N水酸化ナトリウ
ム水溶液33.5mlとエタノール10mlの混液に溶か
し、室温で17時間かき混ぜた。反応液を減圧下に
濃縮乾固し、残留物を塩化メチレンで抽出したの
ち、活性炭で処理をした。減圧下に溶媒を留去
し、油状物として２−ヒドロキシ−Ｎ−〔２−（２
−ピロリル）エチル〕アセトアミド8.2ｇを得た。Infrared absorption spectrum (liquid film) 3300cm -1 , 1740cm -1 , 1660cm -1 Nuclear magnetic resonance spectrum (90MHz, CDCl 3 ) δ: 2.02 (s, 3H), 2.74 (t, 2H), 3.42 (q, 2H) , 4.43 (s, 2H), 5.75-6.8 (m, 4H), 8.93 (br.s, 1H) 10.7 kg of 2-acetoxy-N-[2-(2-pyrrolyl)ethyl]acetamide in 2N aqueous sodium hydroxide solution It was dissolved in a mixture of 33.5 ml and 10 ml of ethanol, and stirred at room temperature for 17 hours. The reaction solution was concentrated to dryness under reduced pressure, the residue was extracted with methylene chloride, and then treated with activated carbon. The solvent was distilled off under reduced pressure to obtain 2-hydroxy-N-[2-(2
8.2 g of -pyrrolyl)ethyl]acetamide were obtained.
赤外線吸収スペクトル（液膜）
3350cm-1，1650cm-1
核磁気共鳴スペクトル（90MHz，CDCl3）
δ：2.73（ｔ，2H），3.45（ｑ，2H），
3.93（ｓ，2H），4.61（ｓ，1H），
5.75〜6.75（ｍ，3H），7.07（ｔ，1H），
8.95（ｓ，1H）
２−ヒドロキシ−Ｎ−〔２−（２−ピロリル）エ
チル〕アセトアミド5.0ｇを無水ベンゼン300mlに
けんだくさせ、室温下にかき混ぜながらＮ，
N′−カルボニルジイミダゾール6.3ｇを加え１時
間反応させたのち、３時間加熱還流させた。冷後
反応液中の不溶物をろ去したのち、水洗し、無水
硫酸マグネシウムで乾燥した。減圧下に溶媒を留
去したのち、残留物をエタノールより再結晶し、
融点130〜132℃の３−〔２−（２−ピロリル）エチ
ル〕−２，４−オキサゾリジンジオン2.9ｇを得
た。Infrared absorption spectrum (liquid film) 3350cm -1 , 1650cm -1 Nuclear magnetic resonance spectrum (90MHz, CDCl 3 ) δ: 2.73 (t, 2H), 3.45 (q, 2H), 3.93 (s, 2H), 4.61 (s , 1H), 5.75-6.75 (m, 3H), 7.07 (t, 1H), 8.95 (s, 1H) 5.0 g of 2-hydroxy-N-[2-(2-pyrrolyl)ethyl]acetamide in 300 ml of anhydrous benzene Stir and bring to room temperature while stirring.
After adding 6.3 g of N'-carbonyldiimidazole and reacting for 1 hour, the mixture was heated under reflux for 3 hours. After cooling, insoluble materials in the reaction solution were filtered off, washed with water, and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was recrystallized from ethanol.
2.9 g of 3-[2-(2-pyrrolyl)ethyl]-2,4-oxazolidinedione having a melting point of 130-132°C was obtained.
元素分析値（C9H10N2O3として）
Ｃ％ Ｈ％ Ｎ％
計算値 55.66 5.19 14.43
実測値 55.49 5.24 14.26
赤外線吸収スペクトル（KBr）
3372cm-1、1810cm-1、1720cm-1
核磁気共鳴スペクトル（90MHz、d6−DMSO）
δ：2.74（ｔ、2H）、3.52（ｔ、2H）、4.70（ｓ、
2H）、5.6〜5.95（ｍ、2H）、6.45〜6.65（ｍ、
1H）、10.53（ｓ、1H）
実施例 ２
２−ピロ−ルカルバルデヒド6.00ｇと３−アミ
ノ−１−プロパノール4.74ｇにベンゼン180mlを
加え、還流液中の水を除去しながら16時間加熱還
流させた。冷後反応液を活性炭で処理したのち、
減圧下に濃縮し、結晶として３−（２−ピロリル
メチレンアミノ）−１−プロパノール9.40ｇを得
た。Elemental analysis value (as C 9 H 10 N 2 O 3 ) C% H% N% Calculated value 55.66 5.19 14.43 Actual value 55.49 5.24 14.26 Infrared absorption spectrum (KBr) 3372cm -1 , 1810cm -1 , 1720cm -1 Nuclear magnetic resonance Spectrum (90MHz, d6 -DMSO) δ: 2.74 (t, 2H), 3.52 (t, 2H), 4.70 (s,
2H), 5.6-5.95 (m, 2H), 6.45-6.65 (m,
1H), 10.53 (s, 1H) Example 2 180 ml of benzene was added to 6.00 g of 2-pyrrolcarbaldehyde and 4.74 g of 3-amino-1-propanol, and heated under reflux for 16 hours while removing water from the reflux liquid. I let it happen. After cooling, the reaction solution was treated with activated carbon,
It was concentrated under reduced pressure to obtain 9.40 g of 3-(2-pyrrolylmethyleneamino)-1-propanol as crystals.
赤外線吸収スペクトル（KBr）
3300cm-1、1640cm-1
核磁気共鳴スペクトル（90MHz、CDCl3）
δ：1.90（quint、2H）、3.67（ｔ、2H）、3.79（ｔ、
2H）、6.1〜7.4（ｍ、5H）、8.04（ｓ、1H）
水素化リチウムアルミニウム5.20ｇをジエチル
エーテル140mlをけんだくさせ、氷冷下にかき混
ぜながら、３−（２−ピロリルメチレンアミノ）−
１−プロパノール6.90ｇをジエチルエーテル200
mlを溶かした液を滴下したのち、2.5時間反応さ
せた。反応後に水を滴下したのち、不溶物をろ去
し、無水硫酸マグネシウムで乾燥したのち減圧下
に溶媒を留去し、油状物として３−（２−ピロリ
ルメチルアミノ）−１−プロパノール5.20ｇを得
た。Infrared absorption spectrum (KBr) 3300cm -1 , 1640cm -1 Nuclear magnetic resonance spectrum (90MHz, CDCl 3 ) δ: 1.90 (quint, 2H), 3.67 (t, 2H), 3.79 (t,
2H), 6.1 to 7.4 (m, 5H), 8.04 (s, 1H) Suspend 5.20 g of lithium aluminum hydride in 140 ml of diethyl ether and stir while cooling on ice to form 3-(2-pyrrolylmethylene amino). −
1-propanol 6.90g diethyl ether 200g
ml of the solution was added dropwise, and the mixture was allowed to react for 2.5 hours. After the reaction, water was added dropwise, and insoluble matter was filtered off. After drying over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 5.20 g of 3-(2-pyrrolylmethylamino)-1-propanol as an oil. I got it.
赤外線吸収スペクトル（液膜）
3300cm-1
核磁気共鳴スペクトル（90MHz、CDCl3）
δ：1.73（quint、2H）、2.88（ｔ、2H）、3.23（ｓ、
2H）、3.80（ｓ、2H）、3.81（ｔ、2H）、5.9〜6.9
（ｍ、3H）、8.91（br、1H）
３−（２−ピロリルメチルアミノ）−１−プロパ
ノール5.10ｇと炭酸水素ナトリウム5.80ｇをジオ
キサン50mlと水50mlの混液にけんだくさせ、氷冷
下にかき混ぜながら、クロル炭酸エチル5.50ｇを
ジオキサン20mlに溶かした液を滴下したのち、２
時間反応させた。反応後を減圧下に濃縮したの
ち、ジエチルエーテルで抽出し、食塩水で洗つた
のち、無水硫酸マグネシウムで乾燥した。減圧下
に溶媒を留去し、油状物としてＮ−（３−ヒドロ
キシプロピル）−Ｎ−（２−ピロリルメチル（カル
バミン酸エチル7.40ｇを得た。Infrared absorption spectrum (liquid film) 3300cm -1 nuclear magnetic resonance spectrum (90MHz, CDCl 3 ) δ: 1.73 (quint, 2H), 2.88 (t, 2H), 3.23 (s,
2H), 3.80 (s, 2H), 3.81 (t, 2H), 5.9-6.9
(m, 3H), 8.91 (br, 1H) Suspend 5.10 g of 3-(2-pyrrolylmethylamino)-1-propanol and 5.80 g of sodium hydrogen carbonate in a mixture of 50 ml of dioxane and 50 ml of water, and cool on ice. While stirring, a solution of 5.50 g of ethyl chlorocarbonate dissolved in 20 ml of dioxane was added dropwise.
Allowed time to react. The reaction mixture was concentrated under reduced pressure, extracted with diethyl ether, washed with brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 7.40 g of N-(3-hydroxypropyl)-N-(2-pyrrolylmethyl(ethyl carbamate) as an oily substance.
赤外線吸収スペクトル（液膜）
3350cm-1、1670cm-1
核磁気共鳴スペクトル（90MHz、CDCl3）
δ：1.29（ｔ、3H）、1.71（quint、2H）、2.10（br、
1H）、3.39（ｔ、2H）、3.56（ｔ、2H）、4.22（ｑ、
2H）、4.36（ｓ、2H）、6.0〜6.8（ｍ、3H）、9.08
（br、1H）
Ｎ−（３−ヒドロキシプロピル）−Ｎ−（２−ピ
ロリルメチル）カルバミン酸エチル7.30ｇとナト
リウムメトキシド0.40ｇをトルエン300ml中で、
還流液中のエタノールを塩化カルシウムで除去し
ながら、17時間加熱か流させた。反応後を活性炭
で処理したのち、減圧下に濃縮し、残留物にジエ
チルエーテルを加え結晶化させたのち、ベンゼン
−ヘキサンより再結晶し、融点61.5〜64℃の３−
（２−ピロリルメチル）テトラヒドロ−2H−１，
３−オキサジン−２−オン26.5ｇを得た。Infrared absorption spectrum (liquid film) 3350cm -1 , 1670cm -1 Nuclear magnetic resonance spectrum (90MHz, CDCl 3 ) δ: 1.29 (t, 3H), 1.71 (quint, 2H), 2.10 (br,
1H), 3.39 (t, 2H), 3.56 (t, 2H), 4.22 (q,
2H), 4.36 (s, 2H), 6.0-6.8 (m, 3H), 9.08
(br, 1H) 7.30 g of ethyl N-(3-hydroxypropyl)-N-(2-pyrrolylmethyl)carbamate and 0.40 g of sodium methoxide were added in 300 ml of toluene.
The reflux solution was heated for 17 hours while removing ethanol with calcium chloride. The reaction mixture was treated with activated carbon, concentrated under reduced pressure, and diethyl ether was added to the residue to crystallize it, which was then recrystallized from benzene-hexane to give 3-
(2-pyrrolylmethyl)tetrahydro-2H-1,
26.5 g of 3-oxazin-2-one was obtained.
元素分析値（C9H12N2O2として）
Ｃ％ Ｈ％ ％
計算値 59.98 6.71 15.55
実測値 59.87 6.74 15.38
赤外線吸収スペクトル（KBr）
3300cm-1、1670cm-1
核磁気共鳴スペクトル（90MHz、CDCl3）
δ：1.8〜2.2（ｍ、2H）、3.36（ｔ、2H）、4.24（ｔ、
2H）、4.38（ｓ、2H）、6.0〜6.9（ｍ、3H）、9.30
（br、1H）
実施例 ３
２−（２−アミノエチル）ピロール1.90ｇ乾燥
塩化メチレン20mlに溶かし、室温でかき混ぜなが
ら、無水コハク酸1.75ｇを乾燥塩化メチレン50ml
に溶かした液を加え、17時間反応させた。析出結
晶をろ取し、塩化メチレンで洗い、融点136〜140
℃の３−〔２−（２−ピロリル）エチルカルバモイ
ル〕プロピオン酸3.45ｇを得た。Elemental analysis value (as C 9 H 12 N 2 O 2 ) C% H% % Calculated value 59.98 6.71 15.55 Actual value 59.87 6.74 15.38 Infrared absorption spectrum (KBr) 3300cm -1 , 1670cm -1 Nuclear magnetic resonance spectrum (90MHz, CDCl 3 ) δ: 1.8-2.2 (m, 2H), 3.36 (t, 2H), 4.24 (t,
2H), 4.38 (s, 2H), 6.0-6.9 (m, 3H), 9.30
(br, 1H) Example 3 1.90 g of 2-(2-aminoethyl)pyrrole was dissolved in 20 ml of dry methylene chloride, and while stirring at room temperature, 1.75 g of succinic anhydride was dissolved in 50 ml of dry methylene chloride.
A solution dissolved in was added to the mixture, and the mixture was allowed to react for 17 hours. Filter the precipitated crystals and wash with methylene chloride to obtain a melting point of 136-140.
3.45 g of 3-[2-(2-pyrrolyl)ethylcarbamoyl]propionic acid at a temperature of 3.45 g was obtained.
赤外線吸収スペクトル（KBr）
3430cm-1、3320cm-1、1695cm-1、1635cm-1
核磁気共鳴スペクトル（90MHz、d6−DMSO）
δ：2.2〜2.8（ｍ、6H）、3.1〜3.45（ｍ、2H）、5.7
〜6.0m、2H）、6.5〜6.65（ｍ、1H）、7.90（ｔ、
1H）、8.35（br、1H）
３−〔２−（２−ピロリル）エチルカルバモイ
ル〕プロピオン酸3.35ｇをキシレン150ml中で17
時間加熱還流させた。冷後、活性炭で処理し、減
圧下に溶媒を留去したのち、残留結晶をベンゼン
−ヘキサンより再結晶し、融点150〜155℃のＮ−
〔２−（２−ピロリル）エチル〕スクシンイミド
2.30ｇを得た。Infrared absorption spectrum (KBr) 3430cm -1 , 3320cm -1 , 1695cm -1 , 1635cm -1 Nuclear magnetic resonance spectrum (90MHz, d6 -DMSO) δ: 2.2-2.8 (m, 6H), 3.1-3.45 (m, 2H), 5.7
~6.0m, 2H), 6.5~6.65 (m, 1H), 7.90 (t,
1H), 8.35 (br, 1H) 3.35 g of 3-[2-(2-pyrrolyl)ethylcarbamoyl]propionic acid in 150 ml of xylene at 17
The mixture was heated to reflux for an hour. After cooling, it was treated with activated carbon and the solvent was distilled off under reduced pressure, and the remaining crystals were recrystallized from benzene-hexane to give N-
[2-(2-pyrrolyl)ethyl]succinimide
Obtained 2.30g.
元素分析値（C10H12N2O2として）
Ｃ％ Ｈ％ Ｎ％
計算値 62.48 6.29 14.58
実測値 62.59 6.29 14.35
赤外線吸収スペクトル（KBr）
3370cm-1、1765cm-1、1690cm-1
核磁気共鳴スペクトル（90MHz、CDCl3）
δ：2.66（ｓ、4H）、2.93（ｔ、2H）、3.78（ｔ、
2H）、5.85〜6.15（ｍ、2H）、6.6〜6.75（ｍ、
1H）、8.45（br、1H）Elemental analysis value (as C 10 H 12 N 2 O 2 ) C% H% N% Calculated value 62.48 6.29 14.58 Actual value 62.59 6.29 14.35 Infrared absorption spectrum (KBr) 3370cm -1 , 1765cm -1 , 1690cm -1 Nuclear magnetic resonance Spectrum (90MHz, CDCl 3 ) δ: 2.66 (s, 4H), 2.93 (t, 2H), 3.78 (t,
2H), 5.85-6.15 (m, 2H), 6.6-6.75 (m,
1H), 8.45 (br, 1H)
Claims (1)
素原子、ｌ及びｎのいずれか一方は１、他の一方
は０又は１、ｍは１〜３の整数、但し、ｌ、ｍ及
びｎの総和が３又は４であり、Ａはピロール環の
２位又は３位に結合するものである）で表される
ピロール誘導体。[Claims] 1. General formula (In the formula, A is alkylene having 1 to 4 carbon atoms, B is an oxygen atom, one of l and n is 1, the other is 0 or 1, m is an integer of 1 to 3, provided that l, m and the sum of n is 3 or 4, and A is bonded to the 2-position or 3-position of the pyrrole ring.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3125884A JPS60174766A (en) | 1984-02-20 | 1984-02-20 | Pyrrole derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3125884A JPS60174766A (en) | 1984-02-20 | 1984-02-20 | Pyrrole derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60174766A JPS60174766A (en) | 1985-09-09 |
| JPH0447666B2 true JPH0447666B2 (en) | 1992-08-04 |
Family
ID=12326323
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3125884A Granted JPS60174766A (en) | 1984-02-20 | 1984-02-20 | Pyrrole derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60174766A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8714873D0 (en) * | 1987-06-25 | 1987-07-29 | Bp Chemicals Additives | Additives |
-
1984
- 1984-02-20 JP JP3125884A patent/JPS60174766A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60174766A (en) | 1985-09-09 |
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