Preparation method of aliskiren

Abstract

The invention discloses a preparation method of aliskiren. Aliskiren is prepared from (R)-t-butylsulfenamide and a compound VIII. The chiral induction effect of the (R)-t-butylsulfenamide is used to construct a required second chiral center and solve the problem of column chromatographic separation needed in the construction of a second chiral center, a third chiral center and a fourth chiral center. The preparation method of aliskiren has the advantages of simple operation, high yield, low cost, high device utilization rate, and suitableness 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 (CASNo: 173334-57-1), the English name is Aliskiren, and its chemical structure is as follows Show: [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 Reagent...

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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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