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Preparing method of 1-(3-benzoyloxy propyl)-5-(2-oxopropyl)-7-indolinecarbonitrile

A technology of benzoyloxypropyl and cyanoindoline, which is applied in the field of preparation of 1--5--7-cyanoindoline, can solve the problem of unsuitability for industrial production, low total yield, There are many synthetic steps to achieve the effect of strong industrial application value, simplified reaction steps and high yield

Active Publication Date: 2012-09-19
LINHAI TIANYU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The biggest disadvantage of this route is that the total yield is very low, only less than 30%, and there are many synthesis steps, which need to be purified by chromatographic columns, so it is not suitable for industrial production

Method used

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  • Preparing method of 1-(3-benzoyloxy propyl)-5-(2-oxopropyl)-7-indolinecarbonitrile
  • Preparing method of 1-(3-benzoyloxy propyl)-5-(2-oxopropyl)-7-indolinecarbonitrile
  • Preparing method of 1-(3-benzoyloxy propyl)-5-(2-oxopropyl)-7-indolinecarbonitrile

Examples

Experimental program
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Effect test

example 1

[0026] Example 1: Put 48g (0.24mol) of 3-chloropropane benzoate, 24g (0.2mol) of indoline (ie compound I), 100ml of DMF, and 24.5g of triethylamine into the flask;

[0027] React at 100 degrees Celsius for 12 hours, and cool to room temperature;

[0028] Water was added to the reaction mixture, extracted with ethyl acetate, the organic layer was washed with water and saturated saline solution, dried with sodium sulfate, and the solvent was distilled off under reduced pressure;

[0029] Add 350ml of acetone to the residue, then add 20ml of hydrochloric acid dropwise with stirring, and stir overnight for crystallization to obtain 51g of compound II hydrochloride with a yield of 80% and a liquid phase purity of 98%.

example 2

[0030] Example two: drop 48g (0.24mol) of 3-chloropropane benzoate, 24g (0.2mol) of indoline (i.e. compound I) in a flask, 100ml of acetone, 26g of potassium carbonate, 2.4g of sodium iodide, and reflux React for 24 hours, cool to room temperature, add 200ml of acetone, filter, rinse with 50ml of acetone, transfer the filtrate to a flask, stir and add 20ml of hydrochloric acid dropwise, stir overnight for crystallization, and obtain 53g of the hydrochloride of compound II, yield It is 83%, and the liquid phase purity is 97%.

[0031] Alternatively, the protecting group can also be benzyl, that is, the reaction raw material is: 45g (0.24mol) of 3-chloropropaneanisole, and the rest remain unchanged. After the reaction, 47g of the hydrochloride of compound II is obtained, and the yield is 81, liquid The phase purity was 98%.

[0032] b. Preparation of 1-(3-benzoyloxypropyl)-5-formyl indoline, i.e. compound III:

[0033] Put 62.5ml of DMF into the reaction bottle, ice bath, add ...

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Abstract

The invention provides a preparing method of a key intermediate 1-(3-benzoyloxy propyl)-5-(2-oxopropyl)-7-indolinecarbonitrile for synthesizing Silodosin. Materials in the whole synthetic route are cheap and easy to obtain, reaction steps are few, the operation is simple, the operation cost is low, yield coefficients of all reaction steps are far higher than those of the existing synthetic route, the preparation method is quite suitable for industrial production and is provided with high industrial application values.

Description

technical field [0001] The present invention relates to a kind of preparation method of 1-(3-benzoyloxypropyl)-5-(2-carbonylpropyl)-7-cyanoindoline, wherein, 1-(3-benzyl Acyloxypropyl)-5-(2-carbonylpropyl)-7-cyanoindoline is a key intermediate for 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-(3-benzoyloxypropyl)-5-(2-carbonylpropyl)-7-cyanoindoline (i.e. compound 8), a key intermediate for the synthesis of silodosin . Japanese invention patent JP200199956 discloses a synthetic route of the compound: [0004] [0005] [0006] The synthetic route uses benzoic acid (i.e. compound 1) as raw material to prepare 1-(3-benzoyloxyprop...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/08
Inventor 宋志刚黄正良王波王成
Owner LINHAI TIANYU PHARMA
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