CN105237416A

CN105237416A - Synthesis method of 5-aminoindanone

Info

Publication number: CN105237416A
Application number: CN201510664348.5A
Authority: CN
Inventors: 陈芳军; 李书耘
Original assignee: Hunan Huateng Pharmaceutical Co Ltd
Current assignee: Hunan Huateng Pharmaceutical Co Ltd
Priority date: 2015-10-14
Filing date: 2015-10-14
Publication date: 2016-01-13

Abstract

The invention relates to a new synthesis method of 5-aminoindanone (compound III), and mainly solves the technical problems of long reaction route, a lot of waste acid and difficult after-treatment, not readily available raw materials and the like in existing synthesis methods. The method provided by the invention includes: reacting aniline (compound I) with 3-chloropropionylchloride to obtain a compound II, and subjecting II to microwave reaction to obtain the compound III.

Description

A kind of synthetic method of 5-amino indanone

Technical field

The invention belongs to organic synthesis field, the synthetic method that particularly a kind of 5-amino indanone is new.

Background technology

5-amino-1-indone and relevant derivative have a wide range of applications in pharmaceutical chemistry and organic synthesis.The synthesis of this compounds at present mainly contains following two kinds of methods synthesis 5-amino-1-indone:

Method A is with 5-acetylaminohydroxyphenylarsonic acid 1-indenes for raw material, with CrO ₃for oxygenant, acetic acid and acetic anhydride make solvent, be obtained by reacting 5-acetylaminohydroxyphenylarsonic acid 1-indone, 5-amino-1-indone (JournalofOrganicChemistry, 1962,27 are obtained again with hydrochloric acid hydrolysis acetamido, 70-76), the method raw material is synthesized by multistep, and reaction produces a large amount of spent acid, unfavorable to environment.

The route of document synthetic method A:

Method B is for raw material with 3-(3-acetylamino phenyl) methyl propionate; 5-amino-1-indone (JournalofMedicinalChemistry is obtained through hydrolysis ester group, carboxyl acidylate, cyclisation, hydrolyzed amide groups; 1976; 19; 472-475); the method synthesis step is many; total recovery is low; carboxyl acylation reaction is used sulfur oxychloride thus is produced a large amount of hydrogenchloride and sulfurous gas; cyclization can produce a large amount of hydrogen chloride gas by friedel-crafts reaction; two-step reaction produces a large amount of spent acid, aftertreatment difficulty.

The route of document synthetic method B:

In sum, there is the shortcomings such as be difficult to obtain or synthetic route is long, the many aftertreatments of spent acid are difficult in the synthetic method raw material of known at present 5-amino-1-indone.

Summary of the invention

The object of the invention is to develop a kind of environmental friendliness, rapidly and efficiently prepare the new preparation method of 5-amido-1-indone.Mainly solve existing raw material to exist and to be difficult to obtain or synthetic route is long, the technical problem of spent acid many aftertreatments difficulty.

Technical scheme of the present invention:

The present invention is obtained by reacting Compound II per with aniline (Compound I) and 3-chlorpromazine chloride, and II obtains compound III by microwave reaction, and reaction formula is as follows:

In above-mentioned technique, the first step reaction conditions is that aniline is dissolved in methylene dichloride, and adds 1 eq of triethylamine and do alkali, and the equivalent that adds of 3-chlorpromazine chloride is 1.1 equivalents, stirs 1 hour at 0 DEG C, more at room temperature stirs 2 hours; Second step reaction conditions is that II is dissolved in acetonitrile, puts into microwave reactor and reacts.

Beneficial effect of the present invention:

The invention solves preparation method's raw material known to be at present difficult to obtain, synthetic route is long, the shortcoming of spent acid many aftertreatments difficulty.Commonly use raw material aniline with industry and 3-chlorpromazine chloride is obtained by reacting Compound II per, II obtains 5-amino-1-indone by microwave reaction, i.e. III.This processing step is short; Reaction does not have spent acid to produce, environmentally friendly; Total recovery is high, can realize the efficient preparation fast of 5-amino-1-indone.

Embodiment

Below provide specific embodiments of the invention, to show possible implementation process, but do not limit the present invention.

Embodiment 1

(1) preparation of Compound II per:

By Compound I and aniline (11g, 0.118mol) be dissolved in 100ml methylene dichloride, add triethylamine (12.9g, 0.118mol), be cooled to 0 DEG C, drip 3-chlorpromazine chloride (14.8g, 0.1mol), 0 DEG C is stirred 1 hour, stirring at room temperature 2 hours, and TLC point plate detection reaction is carried out complete, reaction solution is successively through washing, 1MNaOH washes, washing, and saturated common salt is washed, anhydrous sodium sulfate drying, cross and filter siccative, concentrating under reduced pressure obtains Compound II per 20.3g, yield 94%.

1HNMR(400MHz，DMSO-d6)：δppm7.36～7.15(m,5H),4.61(s,1H),3.63(t,2H),2.31(t,2H)；m/z＝184(M+H)+。

(2) preparation of compound III:

Compound II per (2g, 0.0109mol) is joined in 30ml acetonitrile, is placed in microwave reactor, be heated to 120 DEG C of stirring reactions 15 minutes, stopped reaction, is cooled to room temperature, add water and ethyl acetate, extraction, leave standstill, layering, separates organic phase, with anhydrous sodium sulfate drying, cross and filter siccative, concentrating under reduced pressure obtains the crude product of compound III, crude product ethanol: the mixed solvent recrystallization of water=70:30, obtain light yellow solid III1.18g, yield 74%.

1HNMR(400MHz，DMSO-d6)：δppm7.81(s,1H),3.04(s,1H),2.66(t,2H),2.18(t,2H)；m/z＝148(M+H)+。

Claims

The preparation method of 1.5-amino-1-indone, is characterized in that comprising the following steps: be obtained by reacting Compound II per with aniline (Compound I) and 3-chlorpromazine chloride, II obtains compound III by microwave reaction, and reaction formula is as follows:
2. the preparation method of 5-amino-1-indone according to claim 1, is characterized in that the first step reaction conditions is that aniline is dissolved in methylene dichloride, and adds 1 eq of triethylamine and do alkali, and the equivalent that adds of 3-chlorpromazine chloride is 1.1 equivalents; Second step reaction conditions is that II is dissolved in N-Methyl pyrrolidone, puts into microwave reactor and reacts.
3. the preparation method of 5-amino-1-indone according to claim 1, it is characterized in that the first step reaction is first stirred 1 hour at 0 DEG C, more at room temperature stir 2 hours, second step temperature of reaction is 120 ~ 150 DEG C, and the reaction times is 10 ~ 20 minutes.