Preparation method of aliskiren

A compound and solvent technology, applied in the field of aliskiren preparation, can solve the problems of low equipment utilization, complicated operation and high cost

Active Publication Date: 2016-05-11
ZHEJIANG LEPU PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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

Method used

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  • Preparation method of aliskiren
  • Preparation method of aliskiren
  • Preparation method of aliskiren

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Experimental program
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Embodiment Construction

[0156] The raw materials and equipment used in the specific embodiment of the present invention are known products obtained by purchasing commercially available products.

[0157] The meaning of the acronym:

[0158] THF: Tetrahydrofuran;

[0159] MTBE: methyl tert-butyl ether;

[0160] TLC: thin layer chromatography;

[0161] DMSO: dimethyl sulfoxide;

[0162] DCM: dichloromethane;

[0163] BF 3 -Et 2 O: boron trifluoride ether solution;

[0164] TMSCN: Trimethylcyanosilane;

[0165] NMMO: N-methylmorpholine-N-oxide;

[0166] TPAP: tetra-n-propylammonium perruthenate.

[0167] Embodiment The preparation method of Aliskiren of the present invention

[0168] Preparation of (R)-3-((S)-2-isopropyl-4-valeroyl)-4-benzyloxazolidin-2-one (compound Ⅱ)

[0169] Add diisopropylamine (60.7g, 0.6mol) and THF (400mL) into a 3L three-necked flask, cool down to -78°C, and slowly add 0.6mol n-butyllithium (240mL, 2.5mol / L n-hexane solution) dropwise under nitrogen protection ), th...

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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...

Claims

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Application Information

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IPC IPC(8): C07C237/22C07C231/02C07C43/215C07C47/277C07C313/06C07D307/28C07C57/03C07C33/025C07C47/21C07C43/23
Inventor 黄永学颜林郭鹏
Owner ZHEJIANG LEPU PHARMA CO LTD
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