Method for preparing vilazodone hydrochloride midbody

A technology for vilazodone hydrochloride and intermediates, which is applied in the field of preparation of vilazodone hydrochloride intermediates, can solve problems such as complicated operation, high cost, and long reaction steps, and achieve high reaction yield, low cost, and easy operation. simple effect

Inactive Publication Date: 2013-06-19
NANJING HUAWE MEDICINE TECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The purpose of the present invention is in order to overcome in the preparation method of the key intermediate 5-(1-piperazinyl)-benzofuran-2-carboxamide of existing vilazodone hydrochloride, reaction step is longer, operation is complicated, Use of flammable precious metal organic reagents, low yield, high cost, unfavorable for industrial production, etc.

Method used

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  • Method for preparing vilazodone hydrochloride midbody
  • Method for preparing vilazodone hydrochloride midbody
  • Method for preparing vilazodone hydrochloride midbody

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Preparation of compound II

[0027] Add bis(2-chloroethyl)amine hydrochloride (1908g, 13.20mol) and compound III (1500g, 7.32mol) to a 20L reaction flask successively, add 15L chlorobenzene and 1L cyclohexanol and stir to dissolve, then Add tetrabutylammonium bromide (1170g, 3.6mol), heat up to 130°C, reflux for 60h, monitor by TLC (dichloromethane:methanol:ammonia=85:10:5) After the reaction compound III basically disappears, stop Heat and cool to room temperature. filter. The filter cake was washed twice with ethanol. Air drying at 45°C gave 1602g of compound II, yield: 85%. h 1 -NMR (DMSO, 500MHz) δ: 1.28-1.30(t, 3H), 2.86-2.89(t, 4H), 3.02-3.04(t, 4H), 3.24(s, 2H), 4.73-4.78(q, 4H ), 7.14-7.16 (t, 3H), 7.40 (s, 1H), 7.44-7.48 (m, 2H), 7.58 (s, 1H), 8.01 (s, 1H).

Embodiment 2

[0029] Preparation of compound I

[0030] Compound II (200 g, 0.65 mol) was added to a 5 L autoclave, followed by 1.5 L of isopropanol. Introduce ammonia gas, pressurize to 0.15Mpa, and react at 10°C for 25h. Monitored by TLC (dichloromethane:methanol:ammonia water=85:10:5), the reaction compound II basically disappeared. The reaction was stopped, the solid was filtered off, and the solid was washed twice with methanol. 121.5 g of compound I was obtained by blast drying at 40° C., with a yield of 76.9%. h 1 -NMR (DMSO, 500MHz) δ: 2.86-2.89(t, 4H), 3.02-3.04(t, 4H), 3.24(s, 2H), 7.14-7.16(t, 3H), 7.40(s, 1H), 7.44-7.48 (m, 2H), 7.58 (s, 1H), 8.01 (s, 1H).

Embodiment 3

[0032] Preparation of compound I

[0033] Compound II (200 g, 0.65 mol) was added to a 5 L autoclave, followed by 1.5 L of ethanol. Ammonia gas was introduced, and the reaction was carried out under normal pressure at 25°C for 30h. Monitored by TLC (dichloromethane:methanol:ammonia=85:10:5) the reaction compound II disappeared. The reaction was stopped and the solid was filtered off. The solid was washed 2 times with methanol. Air drying at 40°C yielded 92.6 g of compound I with a yield of 78.6%. h 1 -NMR (DMSO, 500MHz) δ: 2.85-2.87(t, 4H), 3.02-3.05(t, 4H), 3.23(s, 2H), 7.14-7.17(t, 3H), 7.40(s, 1H), 7.44-7.49 (m, 2H), 7.58 (s, 1H), 8.01 (s, 1H).

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Abstract

The invention provides a method for preparing vilazodone hydrochloride midbody. The method comprises the steps of: based on 5-amino coumarone ethyl formate as an initial raw material, reacting with bi(2-chloroethy) benzylamine hydrochloride under the effect of tetrabutylammonium bromide to generate compound II, and reacting with ammonia to prepare compound I 5-(1-piperazinyl)-benzofuran-2-formamide. The used method is easy in raw material obtaining, low in cost, high in reaction yield, simple to operate and suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of preparation of key pharmaceutical intermediates, and in particular relates to a preparation method of a vilazodone hydrochloride intermediate. Background technique [0002] The chemical name of Vilazodone is 5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]-1-piperazinyl]-2-benzofurancarboxamide, which is A dual-action selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist developed by Trovis Pharmaceuticals LLC of the United States, its hydrochloride trade name is Viibryd. In January 2011, the U.S. Food and Drug Administration (FDA) approved Vilazodone Hydrochloride Tablets for the treatment of adults with moderate-to-severe depressive disorder (MDD). Features such as no sexual dysfunction side effects for patients have brought new hope for adults with MDD. [0003] In patents CN1056610C, CN155568C, CN1181067C, WO2006 / 114202, CN101163698A and CN102267985A, 3-(4-R-butyl)indole-5-formonitrile and...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/85
Inventor 徐峰吴起光蒋玉伟包金远张孝清
Owner NANJING HUAWE MEDICINE TECH DEV
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