Method for synthesizing silodosin

A technology of silodosin and a synthesis method, which is applied in the field of preparation of silodosin, a drug for the treatment of benign prostatic hyperplasia, can solve the problems of difficult reaction operation, unfavorable industrial production, complicated preparation process, etc., and achieve simplified labor intensity and easy The effect of industrial production and controllable optical purity

Active Publication Date: 2014-02-05
LIANYUNGANG GUIKE PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0024] The technical problem to be solved by the present invention is that when preparing silodosin in the prior art, due to the complicated preparation process and the need for procedures such as column chromatography, chiral resolution is required during the synthesis of intermediates, resulting in difficult reacti

Method used

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  • Method for synthesizing silodosin
  • Method for synthesizing silodosin
  • Method for synthesizing silodosin

Examples

Experimental program
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Example Embodiment

[0043] Example 1, a method for synthesizing silodosin, the steps are as follows: starting with 7-cyanoindoline, introducing benzoyloxypropyl group at position 1 of indoline, and synthetically prepared 1-(Benzoyloxypropyl)-7-cyanoindoline compound (I), and 2R-2-[(phenylmethyl)amino]-propionyl chloride compound (II) by Friedel-Crafts The key chiral intermediate 5-[(2R)-2-(benzylamino)-1-acetone]-1-[3-(benzoyloxy)propyl]-7-cyanide was synthesized by acylation reaction Indoline compound (III) is reduced by triethylsilane to obtain 5-[(2R)-2-(benzylamino)propyl]-1-[3-(benzoyloxy)propyl]- The 7-cyanoindoline compound (IV) is then catalytically hydrogenated to obtain (R)-1-[1-(3-benzoyloxypropyl)-5-(2-aminopropyl)7- Cyano]indoline compound (V) is condensed with 2-(2,2,2,-trifluoroethoxy)phenoxyethyl methanesulfonate compound (VI) under alkaline conditions to obtain 1 -(3-(4-Fluorobenzoyl)hydroxypropyl)-5-((2R)-2-(2-(2-(2,2,2-trifluoroethoxy)phenoxy)ethylamine Group) propyl) indolin...

Example Embodiment

[0044] In Example 2, the method described in Example 1: Take 7-cyanoindoline as a raw material and react with 3-chloropropyl benzoate to prepare a compound of formula (I), the specific steps are as follows: 1.0 part by weight 3-chloropropyl benzoate and 1.6 parts by weight of 7-cyanoindoline are reacted in 5-10 times the amount of polar solvent at 80-100℃ for 10-15 hours, and finally hydrochloric acid is added to form a salt. Compound (I) hydrochloride; the polar solvent is selected from DMF or DMSO, and an acid shrinking agent is added to DMF or DMSO.

Example Embodiment

[0045] Example 3, in the method described in Example 2: The acid condensation agent added in DMF or DMSO is 0.84 parts by weight of triethylamine or pyridine.

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Abstract

The invention discloses a method for synthesizing silodosin. The method comprises the following steps: by taking 7-cyanoindoline as an initial raw material, synthesizing a 1-(benzoyloxypropyl)-7-cyanoindoline compound (I); reacting with a compound (II) to synthesize a key chiral intermediate 5-[(2R)-2-(benzylamino)-1-acetone]-1-{3-(benzoyloxy)propyl]-7-cyanoindoline compound (III), and reducing through triethyl silicane to obtain a compound (IV); performing catalytic hydrogenation to obtain a compound (V), carrying out a condensation reaction with a compound (VI) under alkaline conditions to obtain a compound (VII), and finally, hydrolyzing under alkaline and H2O2 conditions to obtain silodosin. The compound (I) and the compound (II) are subjected to chiral synthesis to obtain the key chiral compound (III), resolution is avoided, and the optical purity is controllable, so that the reaction yield is greatly improved, the reaction conditions are mild, generation of byproducts in a conventional process is avoided, the production cost is reduced, and the purity is high. The labor intensity is alleviated, the method is environment-friendly and easy for industrial production, and the total yield is high and is improved from 20 percent in a literature report to be about 43 percent.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a preparation method for synthesizing silodosin, a drug for treating benign prostatic hyperplasia. Background technique [0002] Silodosin (Silodosin) is a selective α1A-adrenergic blocker. Preclinical studies have shown that its selective effect on the urethra is 12 and 7.5 higher than that of Prazosin (Prazosin) and Tamsulosin (Tamsulosin). times. Silodosin can significantly inhibit norepinephrine-induced human prostate contraction; it has a dose-dependent inhibitory effect on bladder hyperactivity in rat benign prostatic hypertrophy model, and can increase the pressure threshold of bladder contraction. These data suggest that, in addition to improving bladder function, silodosin is also effective in relieving symptoms associated with benign prostatic hypertrophy. [0003] Benign prostatic hyperplasia (BPH) is a common disease in elderly men, characterized by non-malignant ...

Claims

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Application Information

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IPC IPC(8): C07D209/08
CPCC07D209/08
Inventor 刘志吉安广王从战
Owner LIANYUNGANG GUIKE PHARMA
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