A kind of synthetic method of silodosin

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 ...

AI Technical Summary

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 reaction operations. Low yield, unfavorable for industrial production and other shortcomings, a new synthetic method of silodosin is provided, which utilizes the method of chiral synthesis to synthesize compound (Ⅲ), simplifies the resolution process, improves the yield, and the product High purity, reduce labor intensity

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