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Preparation method for Mitiglinide calcium

A mitiglinide calcium and action technology, which is applied in the preparation field of mitiglinide calcium to achieve the effects of reducing environmental pollution, friendly reaction conditions and high yield

Inactive Publication Date: 2013-01-30
DISHA PHARMA GRP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved in the present invention is to optimize the preparation method of mitiglinide calcium disclosed in the Chinese patent application number 201010573666.8, and provide a preparation method of mitiglinide calcium to reduce material consumption and environmental pollution Or the reaction environment is friendly and the yield is increased

Method used

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  • Preparation method for Mitiglinide calcium
  • Preparation method for Mitiglinide calcium
  • Preparation method for Mitiglinide calcium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Step 1: Preparation of 2-benzylidene succinic acid.

[0026] Feeding amount

[0027] raw material

molecular weight

Feeding amount

moles

The molar ratio of

Dimethyl succinate

146

5.85kg

40.1

1

Benzaldehyde

106

2.12kg

20

0.5

Sodium methoxide

54

1.52kg

28.1

0.7

Methanol

-

5.7L

--

--

caustic soda

40

2.3kg

57.5

1.4

hydrochloric acid

36.5

8.7L

88.7

2.2

[0028] Put dimethyl succinate, methanol, and sodium methoxide into the reaction kettle in turn, start stirring, turn on the heating system of the reaction kettle, and after reflux, add benzaldehyde dropwise. Continue to stir and reflux for a period of time, then heat to evaporate methanol, cool to room temperature, add about 23L caustic soda solution, heat to reflux for 1 hour, cool to room temperature, add ethyl acet...

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Abstract

The invention relates to a preparation method for a bulk drug, i.e., Mitiglinide calcium, used for treating type II diabetes mellitus. According to the invention, improvement of the prior art is carried out: sodium methoxide is used to replace metallic sodium in the prior art, so reaction conditions are friendlier, and industrial production is easier to operate; the usage amount of benzaldehyde is reduced and argon protection is avoided, so environmental protection is benefited, and reaction yield is increased; and the usage amount of a palladium carbon (Pd / C) catalyst is reduced, which enables environmental pollution caused by excess usage of the heavy metal palladium to be reduced and cost to be lowered down.

Description

[0001] Technical field The present invention relates to a preparation method of mitiglinide calcium raw material medicine for treating type II diabetes. Background technique [0002] Miglinide calcium, Chinese chemical name: (+)-bis[(2S)-2-benzyl-4-oxo-4-(cis-perhydroisoindol-2-yl)butyrate]calcium. This product can be used alone for patients with type II diabetes whose hyperglycemia cannot be effectively controlled by diet and exercise therapy. Miglitide calcium is the third meglitide drug after repaglinide and nateglinide, and it is a derivative of phenylalanine. [0003] The compound was synthesized by Japan Tachibana Pharmaceutical Co., Ltd., and was applied for in December 2002 to control postprandial blood sugar in patients with type II diabetes, and was launched in Japan in April 2004. [0004] Chinese patents with application numbers 20061011970.7, 200710064579.8, 201010573659.8, 201010573666.8, 201110344642.X and other Chinese patents disclose the preparation methods ...

Claims

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Application Information

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IPC IPC(8): C07D209/44
Inventor 宋明强丁艳
Owner DISHA PHARMA GRP
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