The preparation method of Aliklen

Abstract

The invention discloses a preparation method of aliskiren, which uses (R)-tert-butyl sulfinamide and compound VIII to prepare aliskiren, and utilizes the chiral induction of (R)-tert-butyl sulfinamide to build a required second chiral center, and solves the problem that column chromatography separation is required when constructing the second, third and fourth chiral centers behind, making the preparation method of Alikren of the present invention simple and convenient to operate, and High efficiency, low cost, high equipment utilization, and suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of Alikren. Background technique [0002] Alikren is a new generation of non-peptide renin blocker, which is a potent, low molecular weight, non-peptide and highly selective renin blocker. Clinically, it is used in the form of Alikren hemifumarate. [0003] The chemical name of Alikren: (2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7 -[4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide (CAS No: 173334-57-1), the English name is Aliskiren, and its chemical structure is as follows Shown: [0004] [0005] In the prior art, the disclosed preparation methods of Alikren are as follows: [0006] US5559111 discloses a preparation method of Alikren hydrochloride, as shown in the synthetic route 1, this method builds four chiral centers by step-by-step stacking method, the route is relatively long, and DIBAL, etc. are required to be used, which is relatively expensive Reage...

AI Technical Summary

Problems solved by technology

[0015] In the methods disclosed in the prior art, when constructing the second, third, and fourth chiral centers, column chromatography is usually required to separate and purify the intermediate product of Alikren, so there are cumbersome operations, high costs, and high yields. Defects such as low efficiency and low equipment utilization

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