Synthesis method for key intermediate of silodosin

Abstract

The invention discloses a synthesis method for a key intermediate of silodosin. The method includes: taking indoline as starting materials, introducing benzoyl oxo propyl into place 1 of the indoline, combining with (R)-2-nitropropionic acid for acylation reaction by means of Friedel-Crafts, placing the synthetic product in trifluoroacetic acid for reduction by the aid of triethyl silicane, introducing formoxyl into place 7 by means of formylation to obtain (R)-1-[1-(3-benzoyl oxo propyl)-5-(2-nitropropyl) 7-formoxyl], reacting in hydroxylamine hydrochloride, pyridine and acetic anhydride, and obtaining the target compound (R)-1-[1-(3-benzoyl oxo propyl)-5-(2-aminopropyl) 7-cyan] indoline by means of catalytic hydrogenation. The synthesis method for the key intermediate of silodosin is rational in design, high in operability, free of chiral synthesis and synthetic route of chiral resolution, shortened in synthetic step and simplified in production operation.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a method for synthesizing a new key intermediate of silodosin. Background technique [0002] Benign prostatic hyperplasia (BPH) is a common and frequently-occurring disease in middle-aged and elderly men. Currently, the drugs used clinically for the treatment of BPH are mainly divided into two categories: α1-adrenoceptor (α-AR) antagonists and 5α-reductase inhibitors. Among them, the α-AR antagonist has the characteristics of rapidity, safety and high efficiency. Silodosin is a BPH α-AR antagonist for the treatment of dysuria caused by benign prostatic hyperplasia. [0003] The synthetic method of the silodosin reported in the prior art mainly contains the following: [0004] The synthesis method reported in patent documents JP200199956 and WO2011124704 uses indoline as a starting material and reacts with 3-chloropropyl benzoate to prepare 1-(3-benzoyloxypropyl)indoline hydro...

AI Technical Summary

Problems solved by technology

The problem with this route is that the synthesis route is long, the total yield of the target compound is low, the induction effect of asymmetric hydrogenation reduction in the route is low, and the key intermediate needs to be separated and recrystallized many times before the pure compound can be obtained. Complicated, not conducive to industrial scale-up production

[0009] Based on the above synthetic process routes, the synthesis of the key intermediate of silodosin (Formula II) requires asymmetric reductive amination and resolution to obtain a high-purity single isomer, wherein the resolution process needs to be repeated many times, and the operation It is cumbersome and the production cost is high, which is not conducive to industrial scale-up production

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