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Preparation method for 1-acetyl-7-cyanopyridine-5-(2-amino propyl) indoline

An aminopropyl and acetyl technology, which is applied in the field of preparation of 1-acetyl-7-cyano-5-(2-aminopropyl) indoline, can solve the problem of poor reaction selectivity in the bromination step, industrial The problems of low value and difficult purification can achieve the effect of strong industrial application value, low implementation cost and high reaction yield.

Inactive Publication Date: 2012-09-26
LINHAI TIANYU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The main shortcoming of this route has three: when a, bromination will use more expensive tribromopyrrolidone; B, two-step hydrogenation reduction reaction all will use expensive catalyst platinum oxide; Low, use column chromatography to separate and purify
[0009] The main disadvantage of this route is that the reaction selectivity of the bromination step is poor, the yield is low, and the purification is relatively difficult
Moreover, the specific process conditions are not disclosed in the patent application text, and only a general introduction to the entire process flow is made, so the industrial value of this route is not high

Method used

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  • Preparation method for 1-acetyl-7-cyanopyridine-5-(2-amino propyl) indoline
  • Preparation method for 1-acetyl-7-cyanopyridine-5-(2-amino propyl) indoline

Examples

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example 1

[0032] Example 1: Put 32.2g of 1-acetylindoline (that is, compound (2)), 94.5g of anhydrous aluminum trichloride and 160ml of dichloroethane into a flask, stir at room temperature, and add 33g of 2-chloropropionyl chloride dropwise .

[0033] After the dropwise addition was completed, the reaction was incubated for 8 hours, and then the reaction mixture was poured into ice water and stirred for 30 minutes.

[0034] The aqueous layer was extracted with dichloroethane, and the organic phases were combined, washed with water, then with saturated brine, and dried over sodium sulfate.

[0035] The solvent was distilled off under reduced pressure, ethanol was added to the residue, and 40.3 g of compound (3) was obtained by recrystallization with a yield of 80%.

example 2

[0036] Example 2: Put 32.2g of 1-acetylindoline (ie compound (2)), 100g of anhydrous zinc chloride and 160ml of dichloromethane into a flask, stir at room temperature, and add 33g of 2-chloropropionyl chloride dropwise.

[0037] After the dropwise addition was completed, the reaction was carried out at 50° C. for 10 hours, and then the reaction mixture was poured into ice water and stirred for 30 minutes.

[0038] The aqueous layer was extracted with dichloromethane, and the organic phases were combined, washed with water, then with saturated brine, and dried over sodium sulfate.

[0039] The solvent was distilled off under reduced pressure, ethanol was added to the residue, and 38 g of compound (3) was obtained by recrystallization with a yield of 78%.

[0040] b: Preparation of 1-acetyl-5-(2-phthalimidopropionyl), compound (4):

[0041] 50 g of compound (3), 48 g of phthalimide potassium salt, and 400 ml of DMF were put into a flask, stirred and heated to 80-100° C., and re...

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Abstract

The invention provides a preparation method for synthesizing 1-acetyl-7-cyanopyridine-5-(2-amino propyl) indoline which is a key intermediate of silodosin. The method comprises the following steps: 1-acetylindoline is adopted to serve as the material, and 1-acetyl-7-cyanopyridine-5-(2-amino propyl) indoline can be obtained through the such 7 steps as friedel-crafts acylation reaction, phthalimide amination, alkylsilane reduction, nitrification, reduction, heavy nitrogen cyaniding and deprotection. According to the method, the materials in the whole synthesizing line are cost-saving and easy to obtain, the operation is simple and the operation cost is low. Moreover, the yield rate of each step of reaction is higher than that in the prior art. Therefore, the method provided by the invention is very suitable for industrial production and has larger industrial application value.

Description

technical field [0001] The present invention relates to a preparation method of 1-acetyl-7-cyano-5-(2-aminopropyl)indoline, wherein, 1-acetyl-7-cyano-5-(2-amino Propyl)indoline is a key intermediate used in the synthesis of silodosin, a drug for benign prostatic hyperplasia. Background technique [0002] Silodosin (silodosin) is an a1 adrenergic receptor antagonist, which has selective inhibitory effect on urethral smooth muscle contraction, and can reduce urethral pressure without significant effect on blood pressure. It is used for the treatment of benign prostatic hyperplasia. [0003] 1-Acetyl-7-cyano-5-(2-aminopropyl)indoline (ie compound (1)), is a key intermediate for the synthesis of silodosin. According to literature reports, in the prior art, there are two main synthetic routes for preparing 1-acetyl-7-cyano-5-(2-aminopropyl)indoline (1): [0004] The first synthetic route is described in European Patent Application Publication No. EP0600675A1: [0005] [00...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/08
Inventor 黄正良宋志刚刘明郑飞
Owner LINHAI TIANYU PHARMA
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