A kind of preparation method and refining method of olanzapine

A refining method, the technology of olanzapine, applied in the direction of organic chemistry, etc., can solve the problems of increasing the difficulty of quality control, limited source of raw materials, increasing production costs, etc., and achieve the effect of high yield, simple process and low pollution

Inactive Publication Date: 2011-12-07
大连美罗大药厂 +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] This method process is simple, shortens reaction time and then reduces energy consumption, but raw material N, N-bis-(2-haloethyl)-methylamine is not easy to get, if prepare raw material again, will increase production cost
[0021] Compared with the three methods, the source of raw materials for the third preparation process is limited; the second method has many by-products, which will inevitably increase the difficulty of quality control; the first method has long reaction time, low yield and high energy consumption. Problems to be Solved Urgently in Realizing Industrialization

Method used

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  • A kind of preparation method and refining method of olanzapine
  • A kind of preparation method and refining method of olanzapine
  • A kind of preparation method and refining method of olanzapine

Examples

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Effect test

Embodiment 1

[0030] The preparation of embodiment 1 olanzapine

[0031] To a 250ml there-necked flask, add 4-amino-2-methyl-10H-thieno[2,3-b][1,5]-benzodiazepine hydrochloride 20.00g (0.075mol), N- Methylpiperazine 75.30 g (0.75 mol) was stirred with nitrogen and heated to reflux for 2 h. The reaction solution was poured into 200 ml of water with stirring, and a light yellow powder solid was precipitated, which was continued to stir for 1 h, filtered and dried to obtain 23.30 g of olanzapine product with a yield of 99.4% and a purity of 99.0% (HPLC).

Embodiment 2

[0032] The purification of embodiment 2 olanzapine

[0033] The 23.30g olanzapine product obtained in Example 1 was transferred into a 250ml single-neck bottle, 240ml of ethanol was added, stirred, and heated to reflux to completely dissolve the product. 0.20g of activated carbon was added to the system, refluxed for decolorization for 30min, filtered, the filtrate was cooled to room temperature for crystallization, filtered and dried to obtain 16.32g of yellow crystalline powder with a yield of 70.0% and a purity of 99.8% (HPLC). .

Embodiment 3

[0034] The preparation of embodiment 3 olanzapine

[0035] Add 4-amino-2-methyl-10H-thieno[2,3-b][1,5]-benzodiazepine hydrochloride 150.03g (0.56mol), N- Methylpiperazine 339.29 g (3.39 mol) was stirred with nitrogen and heated to reflux for 2 h. The temperature is lowered, and more than 70% excess N-methylpiperazine is recovered by distillation under reduced pressure to obtain the solid crude olanzapine.

[0036] Add 400 ml of ethanol to the three-necked flask, and heat to reflux to completely dissolve the solid. The ethanol solution of olanzapine was then poured into 1000 ml of water under stirring, and a light yellow powder solid was precipitated, which was filtered and dried to obtain 173.87 g of olanzapine product with a yield of 99.4% and a purity of 98.9% (HPLC).

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Abstract

The invention relates to a preparation method and a refining method of olanzapine, belonging to the field of medicine preparation. 4-amino-2-methyl-10H-thieno[2,3-b][1,5]-benzodiazepine hydrochloride and N-methylpiperazine reflux reaction, or in diethylene di Refluxing reaction in alcohol dimethyl ether, after the reaction is over, vacuum distillation recovers excess N-methylpiperazine or vacuum distillation recovers excess N-methylpiperazine and diethylene glycol dimethyl ether solvent to obtain olanzapine solid The crude product is recrystallized with ethanol aqueous solution, filtered and dried to obtain the olanzapine product; then dissolved with ethanol under reflux, decolorized with a decolorizing agent, filtered, and the filtrate is cooled to room temperature for crystallization, filtered and dried to obtain refined olanzapine. The invention has the advantages of avoiding highly toxic solvents in the preparation process, little pollution and safe operation; fast reaction, reducing energy consumption; recovering excessive raw materials and solvents, appropriately reducing costs; high yield; olanzapine The refined product has high purity (>99.5%, HPLC) and stable quality.

Description

technical field [0001] The invention relates to a preparation method and a purification method of olanzapine, and belongs to the field of pharmaceutical preparation. Background technique [0002] 2-Methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]-benzodiazepine, hereinafter referred to as "olanzapine" "Ping", a new type of atypical antipsychotics. Olanzapine acts on the central nervous system and is a thiophene benzodiazepine class of serotonin and dopamine receptor dual antagonists. It was developed by Eli Lilly and was first listed in the United States in 1996. The structural formula is as follows (I). [0003] [0004] Patent US5229382 studies olanzapine and its preparation method separately, and discloses two methods for preparing olanzapine, including: (a) N-methylpiperazine reacts with the compound of formula (III): [0005] [0006] In the formula, Q can be -NH 2 , -OH, -SH, where -NH 2 optimal. This process is characterized in that III is reacted w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04
Inventor 孟庆伟崔道平张成海黄积辉汪科元董述祥刘召鹏王亚坤姚鸿杰
Owner 大连美罗大药厂
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