KR840000368B1 - Synthesis of 2-isopropylamino-pyrimidine - Google Patents

Synthesis of 2-isopropylamino-pyrimidine Download PDF

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KR840000368B1
KR840000368B1 KR1019800002411A KR800002411A KR840000368B1 KR 840000368 B1 KR840000368 B1 KR 840000368B1 KR 1019800002411 A KR1019800002411 A KR 1019800002411A KR 800002411 A KR800002411 A KR 800002411A KR 840000368 B1 KR840000368 B1 KR 840000368B1
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pyrimidine
synthesis
isopropyl
isopropylamine
isopropylamino
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KR830002729A (en
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데모스떼느 끌로드
아스피시 그리스챤
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쏘시에테 드 에듀드 드 프로듀트 쉬미크
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom

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Abstract

2-Isopropylaminopyrimidine was prepd. Thus, 10g 2-methyl thiopyrimidine in 100ml H2O was treated with Cl gas, adjusted to pH 8.0 with K2CO3, extd., and dried with Na2SO4 to give 11.3g 2-methylsulfonyl-pyrimidine. 2g of the latter compd. was dissolved in 20ml isopropylamine and refluxed. After 1 hr, isopropylamine of the resulting mixt. was removed and 100mL H2O was added. The soln. was adjusted to pH 9.0 with H2CO3, extd., and dried with Na2SO4 to give 1.7g 2-isopropyl-aminopyrimidine in ˜100% yield.

Description

[발명의 명칭][Name of invention]

2-이소프로필 아미노-피리미딘의 합성법Synthesis of 2-isopropyl amino-pyrimidine

[발명의 상세한 설명]Detailed description of the invention

본 발명은 2-이소프로필 아미노-피리미딘의 합성법에 관한 것이다.The present invention relates to the synthesis of 2-isopropyl amino-pyrimidine.

2-이소프로필 아미노-피리미딘에 대한 다수 합성법이 제안되어져 왔는 바, 2-클로로 피리미딘을 이소프로필 아민으로 아미노리시스하는 방법과, N-이소프로필 구아니딘을 1,1,3,3-테프라에톡시프로판으로 환화하는 방법이 있다.Numerous synthesis methods for 2-isopropyl amino-pyrimidine have been proposed, including the method of aminolysing 2-chloro pyrimidine with isopropyl amine and 1,1,3,3-tepra of N-isopropyl guanidine. There is a method of cyclization to ethoxy propane.

1979년 6월 15일자 유럽 특허출원 제79400393.9호에는 아세톤의 존재하에 2-아미노 피리미딘에 알카리보로 하이드라이드 및 카복실산을 작용시키는 2-이소프로필 아미노-피리미딘의 합성법이 기술되어 있다.European Patent Application No. 79400393.9 dated June 15, 1979 describes the synthesis of 2-isopropyl amino-pyrimidine with the action of an alkali hydride and carboxylic acid on 2-amino pyrimidine in the presence of acetone.

따라서, 본 발명은 이소프로필 아민을 사용하여 2-메틸 설포닐-피리미딘을 아미노리시스하여 2-이소프로필 아미노-피리미딘을 합성하는 방법을 제공하게 되었다. 본 발명에 따라서, 용매없이 이소프로필 아민과 2-메틸 설포닐-피리미딘을 환류시킴으로서 아미노리시스를 실시하게 된다. 이 방법으로, 2-이소프로필 아미노-피리미딘이 실질적으로 정량적인 수올로 얻게 되었다.Accordingly, the present invention provides a method for the synthesis of 2-isopropyl amino-pyrimidine by aminolising 2-methyl sulfonyl-pyrimidine using isopropyl amine. According to the invention, aminolisis is effected by refluxing isopropyl amine and 2-methyl sulfonyl-pyrimidine without solvent. In this way, 2-isopropyl amino-pyrimidine was obtained with substantially quantitative water.

출발물질인 2-메틸설포닐-피리미딘은 Brown D. J. ＆ Ford P. W.(J. Chem.Soc (C) 1967 568)에 의거하여 2-메틸티오-피리미딘으로부터 출발하여 50% 수올로 합성된다. Brown 및 Ford에 의해 기술된 방법은 0°-5℃에서 2-메틸티오-피리미딘의 수성 헌탁액에 염소 기포를 통과시키는 것으로 구성되어 있다.The starting material 2-methylsulfonyl-pyrimidine is synthesized as 50% sool starting from 2-methylthio-pyrimidine according to Brown D. J. & Ford P. W. (J. Chem. Soc (C) 1967 568). The method described by Brown and Ford consists of passing chlorine bubbles through an aqueous suspension of 2-methylthio-pyrimidine at 0 ° -5 ° C.

이 방법은 염소를 더욱 서서히 통과시키고 반응 온도를 -5℃에서 0℃까지 내림으로서 개선되어져 왔는바, 거의 90%의 수올로 얻게 되었다.This method has been improved by passing chlorine more slowly and lowering the reaction temperature from -5 ° C to 0 ° C, resulting in almost 90% of the sool.

Boarland M.P.V. 및 McOmie J.P.W. (J. chem. Soc. 1952, 3716)에 의해 처음 기술된, 2-메르캅토-피리미딘으로부터 출발하는 2-메틸티오-피리미딘의 제법은 62% 수올로 얻을 수 있으며, Hunig S. 및 Oette K.F. (Liebig's Annalen der Chemie, 1961, 640, 98)에 의한 방법은 83% 수올로 얻을 수 있다.Boarland M.P.V. And McOmie J.P.W. The preparation of 2-methylthio-pyrimidine starting from 2-mercapto-pyrimidine, first described by (J. chem. Soc. 1952, 3716), can be obtained with 62% sool, Hunig S. and Oette KF (Liebig's Annalen der Chemie, 1961, 640, 98) can be obtained with 83% sool.

Dou, H.와 그의 동료(인 황 및 관련원소, 1977, 3, 355)의 상 전이 촉매법은 2-메틸티오-피리미딘을 정량적인 량으로 얻을 수 있다.Phase transfer catalysis of Dou, H. and his colleagues (phosphorus and related elements, 1977, 3, 355) can yield quantitative amounts of 2-methylthio-pyrimidine.

다음 반응 도식은 2-메르캅토-피리미딘으로부터 출발하는 합성법을 도시한 것이다.The following scheme depicts the synthesis starting from 2-mercapto-pyrimidine.

Figure kpo00001
Figure kpo00001

본 발명을 실시예에 의거 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in detail with reference to Examples.

[실시예 : ]Example

(a) 2-메틸설포닐-피리미딘의 합성(a) Synthesis of 2-methylsulfonyl-pyrimidine

200ml 용량의 반용기에 10g(0.0794몰)의 2-메틸티오 피리미딘 및 100ml의 물에 주입하였다.A 200 ml volume half vessel was injected into 10 g (0.0794 moles) of 2-methylthio pyrimidine and 100 ml of water.

약간 0℃이하에서, 염소기포를 서서히 통과시킨지 5분 후에 얻은 용액에 염소기포를 계속 서서히 통과시키면서 1시간 동안 실온을 유지하였다. 반응이 진행되는 동안 박층 크로마토그래피로 확인하여 염소 공급을 중단시킨 후 플라스크를 0℃에서 1시간 동안 진탕하였다. K2CO3를 사용하여 pH를 8로 조절하고 염소화 용매로 추출하였다. Na2SO4를 사용하여 유기상을 건조시키고 용매를 제거하였다.At slightly below 0 ° C., the room temperature was maintained for 1 hour while the chlorine bubbles were continuously passed slowly through the solution obtained 5 minutes after the chlorine bubbles were slowly passed. The reaction was stopped by thin layer chromatography to stop the chlorine feed and the flask was shaken at 0 ° C. for 1 hour. The pH was adjusted to 8 with K 2 CO 3 and extracted with chlorinated solvent. The organic phase was dried using Na 2 SO 4 and the solvent was removed.

에탄올로 2번 재결정하여 백색 생성물을 얻었다.Recrystallization twice with ethanol gave a white product.

수올 11.3g : 90%. 응점 70.72℃ (lit 73-74℃).Water 11.3 g: 90%. Dew point 70.72 ° C. (lit 73-74 ° C.).

(b) 2-이소프로필 아미노-피리미딘의 합성(b) Synthesis of 2-isopropyl amino-pyrimidine

2g(0.0126몰)의 2-메틸설포닐-피리미딘을 20ml의 이소프로필아민에 현탁시켰다.2 g (0.0126 moles) of 2-methylsulfonyl-pyrimidine was suspended in 20 ml of isopropylamine.

환류를 실시하여 신속히 용액을 얻고, 1시간 후(반응의 경과를 박충크로마토그래프로 확인한다), 환류를 중지하여 과량의 이소프로필아민을 제거하였다. 100ml의 물을 가하고 탄산수를 사용하여 pH를 9로 조절하였다.Reflux was carried out quickly to obtain a solution, and after 1 hour (checking the progress of the reaction with a depleted chromatography), reflux was stopped to remove excess isopropylamine. 100 ml of water was added and the pH was adjusted to 9 using carbonated water.

염소화용매를 추출하여, 유기상을 Na2SO4상에서 건조시키고 용매를 증별하여 1.7g의 생성물(~100% 수율)을 얻었다. 생성물은 구 자체로서 또는 그의 염 형태로 사용될 수 있다.The chlorinated solvent was extracted, the organic phase was dried over Na 2 SO 4 and the solvent was partitioned to give 1.7 g of product (˜100% yield). The product can be used as the sphere itself or in the form of its salts.

Claims (1)

용매의 부재하에 화학량론비의 이소프로필아민 및 2-메틸설포닐-피리미딘을 환류시키는 것으로 구성된, 아미노리시스에 의해 2-이소프로필아미노 피리미딘을 합성하는 방법.A method for synthesizing 2-isopropylamino pyrimidine by aminolysis, consisting of refluxing stoichiometric ratios of isopropylamine and 2-methylsulfonyl-pyrimidine in the absence of solvent.
KR1019800002411A 1980-06-19 1980-06-19 Synthesis of 2-isopropylamino-pyrimidine KR840000368B1 (en)

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