Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method for Mitiglinide calcium hydrate

A mitiglinide calcium and reaction technology, which is applied in the field of medicine, can solve problems such as being unsuitable for industrial production, and achieve high industrial production value, mild reaction conditions, and high yield.

Inactive Publication Date: 2014-04-16
中国人民解放军联勤保障部队第九六六医院
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Miglinide calcium is an excellent quick-acting hypoglycemic drug. Although there are many synthetic routes reported, most of them are not suitable for industrial production. It is of great significance to find an economical and effective preparation method

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method for Mitiglinide calcium hydrate
  • Preparation method for Mitiglinide calcium hydrate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Add cis-hexahydroisoquinoline (250.4g, 2mol), anhydrous potassium carbonate (304.0g, 2.2mol), dichloromethane (1000ml) into the reaction flask, keep the temperature at 0-5°C, and stir vigorously, Add a solution of chloroacetyl chloride (271.0g, 2.4mol) in dichloromethane (500ml) dropwise, after the drop, react at room temperature for 2.5h, spot plate monitoring, after the reaction is complete, add 1000ml of water, separate the organic layer, wash with water (1000ml), Wash with saturated brine (1000ml), dry with anhydrous sodium sulfate overnight, distill off dichloromethane under reduced pressure to obtain cis-N-chloroacetylhexahydroisoindole (2) 357.4g oil, yield: 88.6%.

[0029] cis-N-chloroacetylhexahydroisoindole (302.5g, 1.5mol), N-phenylpropionylcamphorsultam (573.0g, 1.65mol), 70% sodium hydride (56.6g, 1.65mol), N,N-Dimethylformamide (900ml) was added into the reaction flask, and stirred vigorously at 50°C for 12h to obtain an alkylated product, which was kept a...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a novel preparation method for Mitiglinide calcium hydrate. The method comprises the following steps: adopting cis-hexahydroisoindole as a raw material, conducting acylation reaction, hydrocarbonylation reaction, hydrolysis reaction, and salt forming reaction on the raw material, and obtaining the Mitiglinide calcium hydrate; a one-port process method is adopted for conducting the hydrocarbonylation reaction and the hydrolysis reaction, and the product purity can reach over 99.8%, and the yield can reach over 36%. The preparation method for Mitiglinide calcium hydrate has the advantages of the easy-to-get raw material, mild reaction condition, simple and practicable operation, and relatively high yield, therefore, the method has relatively higher industrial production value, and industrialization has been realized at present.

Description

technical field [0001] The invention relates to the field of medicine, in particular, the invention relates to a preparation method of mitiglinide calcium. Background technique [0002] Bis[(2s)-2-benzyl-3-(cis-hexahydroisoindole-2-carbonyl)propanoic acid] monocalcium dihydrate (mitiglinide calcium), molecular formula C 38 h 48 CaN 2 o 6 2H 2 O, the English name is Mitiglinide Calcium Hydrate, and its structural formula (I) is as follows: [0003] [0004] Miglinide Calcium was synthesized by Japan Tachibana Pharmaceutical Co., Ltd. and launched in Japan in April 2004. It is used for type Ⅱ diabetic patients whose hyperglycemia cannot be effectively controlled by diet and exercise therapy. Miglinide calcium is the third meglitide drug after repaglinide and nateglinide, which is a derivative of phenylalanine. Miglinide calcium closes the ATP-dependent K channel on the pancreatic β-cell membrane, causing Ca influx, increasing the intracellular Ca concentration and deg...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/44
CPCC07D209/44
Inventor 苑振亭王绍杰
Owner 中国人民解放军联勤保障部队第九六六医院