Process for preparation of benazepril

A kind of amino tert-butyl ester, high-purity technology, applied in the direction of organic chemistry, etc., can solve the problems of high raw material quantity, uneconomical, etc., and achieve the effect of improving yield and yield

Inactive Publication Date: 2006-09-06
RANBAXY LAB LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method does not disclose the synthesis of benazepril or its physiologically acceptable salts using II
Furthermore, the amount of raw materials disclosed for the preparation of II is significantly high, which is not economical from a commercial point of view

Method used

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  • Process for preparation of benazepril
  • Process for preparation of benazepril
  • Process for preparation of benazepril

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Embodiment 1: Use 10% palladium on carbon and hydrogen to prepare high-purity (±) 1-tert-butoxycarbonylmethyl-3-amino-2,3,4,5-tetrahydro-1h-[ 1) Benzazepan-2-one

[0093]To 1-tert-butoxycarbonylmethyl-3-azido-2 shown in formula IV, 3,4,5-tetrahydro-1H-[1] benzazepan-2-ketone (5 grams , 15.8 mmol) in methanol (25 milliliters) solution, add 10% palladium on carbon (0.5 gram, 50% by weight), the compound shown in the formula IV comprises 1-tert-butoxycarbonylmethyl- 7-Bromo-3-azido-2,3,4,5-tetrahydro-1H-[1]benzazepan-2-one as impurity (7.67%). The mixture was stirred under 40-50 psi hydrogen atmosphere with periodic evacuation at room temperature. After 16 hours, the reaction mass was filtered through a bed of celite to remove palladium on carbon and the filtrate was concentrated to dryness in vacuo to afford the title product as a viscous oil which solidified on storage.

[0094] Yield: 4.5 g, 98%

[0095] Purity: 87.47%

[0096] Impurity IIa: Not detected by HPLC. ...

Embodiment 2

[0097] Example 2: Use 10% palladium on carbon and ammonium formate as the hydrogen source to prepare high-purity (±) 1-tert-butoxycarbonylmethyl-3-amino-2,3,4,5-tetrahydro shown in formula II -1h-[1]benzazepan-2-one

[0098] 1-tert-butoxycarbonylmethyl-3-azido-2,3,4,5-tetrahydro-1H-[1]benzazepan-2-one (5 grams, 15.8 mmol) in methanol (25 milliliters) solution, add ammonium formate (10.0 g, 15.75 mmol), the compound shown in the formula IV comprises 1-tert-butoxycarbonylmethyl-7-bromo- 3-Azido-2,3,4,5-tetrahydro-1H-[1]benzazepan-2-one is as impurity, and described solution comprises palladium on carbon catalyst (0.5 gram, 10%, 50 %weight). The temperature of the reaction mass was slowly raised to 40-50°C and stirred at this temperature for 16 hours. After the completion of the reaction was confirmed by TLC, the catalyst was removed by filtration, the filtrate was concentrated under vacuum, and the residue was dissolved in dichloromethane (50 mL) and water (50 mL). Separate ...

Embodiment 3

[0102] Example 3: Preparation of high-purity (±) 1-tert-butoxycarbonylmethyl-3-amino-2,3,4,5-tetrahydro-1h-[1]-benzazepine shown in formula II Heptan-2-one

[0103] Part a: Preparation of (±)1-tert-butoxycarbonylmethyl-3-azido-2,3,4,5-tetrahydro-1h-[1]benzazepane-2 represented by formula II -ketone

[0104] 1-tert-butoxycarbonylmethyl-3-azido-2,3,4,5-tetrahydro-1H-[1]benzazepan-2-one (5 grams, 15.8 mmol) in methanol (25 milliliters) solution, add Raney nickel (0.82 gram), the compound shown in the formula IV comprises 1-tert-butoxycarbonylmethyl-7-bromo-3-azide shown in the formula IVa -2,3,4,5-Tetrahydro-1H-[1]benzazepan-2-one as an impurity (7.67%). The mixture was stirred under a hydrogen atmosphere at a pressure of 40-50 psi, periodic venting, and 50-55°C. After 16 hours, the reaction mass was filtered through a bed of celite to remove Raney nickel, and the filtrate was concentrated to dryness under vacuum to afford the title product as a viscous oil which solidified o...

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PUM

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Abstract

The present invention relates to an improved process for preparation of highly pure benazepril of Formula I, wherein R is hydrogen or pharmacologically acceptable salt thereof by completely eliminating the impurity of 7-bromo analogue of benazepril of Formula Ia, wherein R is bromo group.

Description

field of invention [0001] The present invention relates to the method for preparing formula (I) benazepril (benazepril) or its physiologically acceptable salt, wherein R is hydrogen, said method comprises removing the 7-bromo analogue of benazepril of formula (Ia) , wherein R is bromo. [0002] [0003] Formula I (R=H) [0004] Formula Ia (R=Br) Background of the invention [0005] Benazepril is (3S)-1-(carboxymethyl)-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino] shown in the attached molecular formula (I) -2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one. It is a well-known long-acting angiotensin-converting enzyme (ACE) inhibitor mainly used in the treatment of hypertension. Benazepril was probably first reported in US Patent 4410520. [0006] Two key intermediates of preparing benazepril are 3-(S)-amino-1-carboxymethyl-2,3,4,5-tetrahydro-1H-[1] benzazepine represented by formula II Cycloheptan-2-one or its 1-carboxymeth...

Claims

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Application Information

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IPC IPC(8): C07D223/16C07D223/00
CPCC07D223/16
Inventor Y·库马S·沙希亚纳拉亚纳S·迪M·雷夫克
Owner RANBAXY LAB LTD
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