Preparation method for lurasidone hydrochloride

A technology of lurasidone hydrochloride and salt formation, which is applied in the field of drug synthesis, can solve the problems of unsuitability for large-scale industrial production, high production process cost, and low yield, and achieve low toxicity, low production process cost, and high yield Effect

Inactive Publication Date: 2017-07-04
SUZHOU ERYE PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Purpose of the invention: To provide a preparation method of lurasidone hydrochloride to solve the problems of high cost, high toxicity, low yield and unsuitability for industrialized large-scale production in the existing production process

Method used

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  • Preparation method for lurasidone hydrochloride
  • Preparation method for lurasidone hydrochloride

Examples

Experimental program
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Embodiment 1

[0024] (1) Using trans-1,2-cyclohexanedicarboxylic acid (SM-1) as raw material to obtain 1R,2R-cyclohexanedicarboxylic acid (SM-2); trans-1,2-cyclohexanedicarboxylic acid (SM-2); Alkanedioic acid and R-(+)-α-phenethylamine reacted at 5°C to form a salt, filtered and dried at room temperature; then recrystallized in a hot ethanol / toluene (1:1) mixed solvent 1 Finally, add hydrochloric acid to free, and extract with ether to obtain (R, R)-1,2-cyclohexanedicarboxylic acid.

[0025] (2) Dimethyl 1R, 2R-cyclohexanedicarboxylate was obtained by methyl esterification; 1R, 2R-cyclohexanedicarboxylic acid was added to 400ml of methanol, concentrated sulfuric acid was added dropwise at room temperature and then heated to reflux for 5 hours of reaction.

[0026] (3) Reduction to obtain 1R, 2R-cyclohexanedimethanol; add 1R, 2R-dimethyl cycloadipate, THF, and NaBH4 into the reaction flask, heat to 45°C, slowly add methanol dropwise, and reflux after dropping After 2.5h, 1R, 2R-cyclohexane...

Embodiment 2

[0032] (1) Using trans-1,2-cyclohexanedicarboxylic acid (SM-1) as raw material to obtain 1R,2R-cyclohexanedicarboxylic acid (SM-2); trans-1,2-cyclohexanedicarboxylic acid (SM-2); Alkanedioic acid and R-(+)-α-phenethylamine reacted at 10°C to form a salt, filtered and dried at room temperature; then recrystallized in a hot ethanol / toluene (1:1) mixed solvent 2 Finally, add hydrochloric acid to free, and extract with ether to obtain (R, R)-1,2-cyclohexanedicarboxylic acid.

[0033] (2) Methyl esterification to obtain dimethyl 1R, 2R-cyclohexanedicarboxylate; add 1R, 2R-cyclohexanedicarboxylic acid to 500ml of methanol, add concentrated sulfuric acid dropwise at room temperature and heat to reflux for 6 hours of reaction.

[0034] (3) Reduction to obtain 1R, 2R-cyclohexanedimethanol; add 1R, 2R-dimethyl cycloadipate, THF, and NaBH4 into the reaction bottle, heat to 40°C, slowly add methanol dropwise, and reflux after dropping 3h, 1R, 2R-cyclohexanedimethanol was obtained after p...

Embodiment 3

[0040] (1) Using trans-1,2-cyclohexanedicarboxylic acid (SM-1) as raw material to obtain 1R,2R-cyclohexanedicarboxylic acid (SM-2); trans-1,2-cyclohexanedicarboxylic acid (SM-2); Alkanedioic acid and R-(+)-α-phenethylamine reacted at 25°C to form a salt, filtered and dried at room temperature; then recrystallized in hot ethanol / toluene (1:1) mixed solvent3 Finally, add hydrochloric acid to free, and extract with ether to obtain (R, R)-1,2-cyclohexanedicarboxylic acid.

[0041] (2) Methyl esterification to obtain dimethyl 1R, 2R-cyclohexanedicarboxylate; add 1R, 2R-cyclohexanedicarboxylic acid to 300ml of methanol, add concentrated sulfuric acid dropwise at room temperature and heat to reflux for 4 hours of reaction.

[0042] (3) Reduction to obtain 1R, 2R-cyclohexanedimethanol; add 1R, 2R-dimethyl cycloadipate, THF, and NaBH4 into the reaction flask, heat to 50°C, slowly add methanol dropwise, and reflux after dropping 2h, 1R, 2R-cyclohexanedimethanol was obtained after post-...

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Abstract

The invention discloses a preparation method for lurasidone hydrochloride. According to the preparation method, trans-1,2-cyclohexanedicarboxylic acid (SM-1) is used as a raw material and subjected to resolution, methyl esterification, reduction, methylsulfonylation, condensation, recrystallization and salt formation so as to eventually obtain lurasidone hydrochloride. The preparation method provided by the invention greatly reduces production cost and has the characteristics of high product yield, easy operation, low toxicity and suitability for industrial large-scale production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a preparation method of lurasidone hydrochloride. Background technique [0002] Lurasidone hydrochloride is a new type of atypical antipsychotic drug developed by Japan's Sumitomo Pharmaceutical Company. Adjunctive treatment of valeric acid for depressive episodes associated with bipolar I disorder in adult patients. In 2014, it was approved by EMA to be listed in the EU. It has a high binding capacity for dopamine D2 receptors and serotonin (5-HT1A, 5-HT2A, 5-HT7) and α2C receptors, with less binding capacity for other receptors. It has significant curative effect on both positive and negative symptoms of psychiatric patients, and studies have reported that lurasidone can improve cognitive function. Causes less weight gain and does not cause changes in glucose, lipids (lipids), ECG and QT intervals. [0003] The chemical name of lurasidone is (3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D417/12
CPCC07D417/12
Inventor 刘志陆文娟王宁
Owner SUZHOU ERYE PHARMA CO LTD
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