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Method for preparing vilazodone or hydrochloride thereof

A kind of technology of vilazodone and compound, applied in the field of preparing vilazodone or its hydrochloride, can solve problems such as low reaction yield

Inactive Publication Date: 2013-01-16
BEIJING TRADE STAR MEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The intermediate 1-(2-R'benzofuran-5-yl)piperazine in this route is prepared from the corresponding 2-R'-5-aminobenzofuran with di(2-chloroethyl)amine in base Under the effect of reaction, the reaction yield of this step is very low, only about 30%

Method used

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  • Method for preparing vilazodone or hydrochloride thereof
  • Method for preparing vilazodone or hydrochloride thereof
  • Method for preparing vilazodone or hydrochloride thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] Preparation of methyl 4-chlorobutyrate

[0080] Take 49.8g of potassium carbonate in 400ml of methanol, cool to 0-5°C with an ice-water bath, add 42.3g of 4-chlorobutyryl chloride dropwise, heat to reflux for 4 hours after the addition, then filter, and distill the filtrate under reduced pressure to obtain 41.2g of crude product , used directly in the next reaction.

[0081] ESI-MS[M+H] + :137.04

[0082] 1 H-NMR (CDCl 3 ): δ1.92-1.96 (m, 2H), 2.31 (t, 2H), 3.30 (t, 2H), 3.68 (s, 3H).

Embodiment 2

[0084] Preparation of 4-bis(2-hydroxyethyl)aminobutyric acid methyl ester

[0085] The 41.2g crude product of methyl 4-chlorobutyrate prepared by the previous step reaction was dissolved in 400ml of acetonitrile, 41.5g of potassium carbonate and 31.5g of bis(2-hydroxyethyl)amine were added, heated to reflux for 12 hours, filtered after cooling, and the filtrate was reduced Distill under pressure, add 400ml isopropanol to the residue, slowly add 30ml (37%) concentrated hydrochloric acid at room temperature, filter after the precipitation is complete, dissolve the filter cake in 200ml water, extract with 3*200ml ethyl acetate, and use anhydrous sulfuric acid for the organic phase It was dried over sodium, filtered and distilled under reduced pressure to obtain 23.4 g of product.

[0086] ESI-MS[M+H] + :206.14

[0087] 1 H-NMR (CDCl 3 ): δ1.68-1.72 (m, 2H), 2.20 (t, 2H), 2.34 (t, 2H), 2.52 (t, 4H), 3.56 (t, 4H), 3.68 (s, 3H).

Embodiment 3

[0089] Preparation of 4-bis(2-chloroethyl)aminobutyric acid methyl ester

[0090] Take 20.5g of 4-bis(2-hydroxyethyl)aminobutyric acid methyl ester and 30.0g of pyridine and dissolve it in 320ml of tetrahydrofuran, cool to 0-5°C, add 27.5g of phosphorus trichloride dropwise, after the addition, heat Reflux for 4 hours, filter after cooling, distill the filtrate under reduced pressure, add 200ml ethyl acetate and 100ml ice water to the residue, adjust the pH to about 7 with 1N sodium hydroxide solution, separate the liquids, dry the organic phase with anhydrous sodium sulfate and filter , The filtrate was evaporated to dryness under reduced pressure to obtain 17.4 g of product.

[0091] ESI-MS[M+H] + :242.07

[0092] 1 H-NMR (CDCl 3 ): δ1.71-1.76 (m, 2H), 2.22 (t, 2H), 2.33 (t, 2H), 2.53 (t, 4H), 3.55 (t, 4H), 3.69 (s, 3H).

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Abstract

The invention relates to a method for preparing 5-(4-[4-(5-cyan-3-indolyl)-butyl]-1-piperazinyl) benzofuran-2-formamide (vilazodone) or hydrochloride thereof. The method comprises the following steps of: performing reaction between a formula-I compound and a formula-II compound 5-amino-2-formamido-benzofuran in a solvent under the action of alkaline matter, and separating and purifying products to obtain a formula-1 compound, i.e. the vilazodone; and salifying the vilazodone and hydrochloric acid in the solvent to prepare vilazodone hydrochloride. The invention also relates to a method for preparing the formula-I compound.

Description

technical field [0001] The present invention relates to a method for preparing vilazodone or its hydrochloride. technical background [0002] At present, several disclosed methods for preparing vilazodone hydrochloride at home and abroad can be summarized into the following two categories: [0003] 1) Patents WO2006 / 114202 and CN101163698A also disclose the use of 3-(4-piperazinebutyl)indole-5-carbonitrile and 5-bromobenzofuran-2-carboxamide as intermediates to prepare vera hydrochloride The oxazolone method. The synthetic route is as follows: [0004] [0005] The method takes 3-(4-piperazinylbutyl) indole-5-carbonitrile and 5-bromobenzofuran-2-carboxamide as intermediates, and three (dibenzylidene acetone)-dipalladium and three Under the catalysis of tert-butylphosphine, the coupling reaction is carried out, and then acidified to form a salt to prepare vilazodone hydrochloride. The method adopts an expensive metal palladium complex catalyst and a tri-tert-butylphosp...

Claims

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Application Information

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IPC IPC(8): C07D405/12
Inventor 李秀平司成桃
Owner BEIJING TRADE STAR MEDICAL TECH
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