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Novel synthesis route of glipizide

The technology of a glipizide and a synthesis method is applied in the preparation field of the hypoglycemic drug glipizide, can solve the problems of difficulty in obtaining starting materials, high cost, unfavorable industrialized production and the like, and achieves environmental friendliness, mild reaction conditions, Post-processing simple effects

Active Publication Date: 2015-06-17
WUHAN WUYAO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The above two reactions adopt one-step reaction to obtain glipizide, which The raw materials are difficult to obtain and the cost is high, which is not conducive to industrial production, and the product needs to be further purified to meet the demand for pharmaceuticals.

Method used

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  • Novel synthesis route of glipizide
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  • Novel synthesis route of glipizide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Preparation of compound III

[0027] Add 3.96 g (0.020 mol) 4-(2-aminoethyl) ammonium benzenesulfonate (compound II) into a 100 ml single-necked flask, and then add 75 ml of DMF and cool to 10°C under ice water bath and stir to dissolve. After dissolution, 4.8g Boc anhydride (0.022mol) was added dropwise to the reaction system at 0-5°C, and the temperature was raised to room temperature for 1.5-2h. After the reaction, the reaction solution was poured into 300 ml of purified water, a white solid was precipitated, and the compound III was dried to obtain 5.58 g of compound III solid with a yield of 93%.

Embodiment 2

[0028] Example 2: Preparation method 1 of compound IV

[0029] Add 5.54g (0.018mol) of compound III, 5.1g (0.037mol) of potassium carbonate, and 200ml of acetone into a 250ml three-necked flask, set up the condenser, stir and heat to reflux, and react for 6-7 hours. After the reaction, 2.78g (0.022mol) cyclohexyl isocyanate was added to the reaction system, and the reflux reaction was continued for 6-7h. After the reaction is completed again, suction filtration, the solid is taken out and transferred to a beaker, a small amount of purified water is added, and the pH is adjusted to 5-6 with 10% HCl solution, and then suction filtered, the solid is washed with purified water, and the compound IV solid is taken out and dried. 7.81g, the yield is 99.36%.

Embodiment 3

[0030] Example 3: Preparation method 2 of compound IV

[0031] Add 5.54g (0.018mol) of compound III, 3.9g (0.037mol) of sodium carbonate, and 200ml of acetone into a 250ml three-necked flask, set up the condenser, stir and heat to reflux, and react for 6-7 hours. After the reaction, 2.78g (0.022mol) cyclohexyl isocyanate was added to the reaction system, and the reflux reaction was continued for 6-7h. After the reaction is completed again, suction filtration, the solid is taken out and transferred to a beaker, a small amount of purified water is added, and the pH is adjusted to 5-6 with 10% HCl solution, and then suction filtered, the solid is washed with purified water, and the compound IV solid is taken out and dried. 7.81g, yield 99.36%

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Abstract

The invention relates to a novel synthesis route of glipizide, which is characterized by comprising the following steps of protecting 4-(2-amino ethyl)benzenesulfonic acid ammonia (II) by Boc anhydride to obtain a compound (III); reacting the compound (III) with cyclohexyl isocyanate to obtain a compound (IV); carrying out deprotection on the compound (IV) to obtain a compound (V); and reacting the compound (V) with 2-methyl-5-pyrazine carboxylic acid to obtain the glipizide (I) with the single impurity which is less than or equal to 0.5% and the high purity which is more than or equal to 99%. The process is simple, the yield is high, the purity is high and the single impurity is low; and the process is environment-friendly and industrial production is easy to realize.

Description

Technical field [0001] The present invention is a pharmaceutical chemistry field, which involves a preparation method for hypoglycemic pyrazine. Background technique [0002] Glitzine: Chemical name is 1-ring-based-3- {4- [2- (5-methyl pyrazine-2-amide) -Teitzide] benzenezate} 脲, the chemical structure is as follows: [0003] [0004] Eline pyrazine is a hypoglycemic drug for non -insulin -dependent (type II) diabetes. It is used for light and moderate non -insulin -dependent patients who have failed to achieve good effects. [0005] There are mainly the following synthesis routes that have been publicly reported: [0006] EP (8585109.2) In hydrophilic alkaline conditions, compounds (ⅵ) and compounds (ⅶ) [0007] (Among them, R1 = NH2, R2 = NHCOCL3) The reaction is used to use N.N-di metamimam (DMF), two metamorea (DMSO), N, N-dimethyliline (DMA) for solvents. The synthesis route is as follows: [0008] WO / 01 05354 A2 in alkaline conditions (ⅸ) under alkaline conditions (ⅸ) a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D241/24
Inventor 皮金红丁友友尹冬魏金维潘文清谢国范
Owner WUHAN WUYAO PHARMA
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