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Method for preparing nevirapine

A nevirapine and reaction technology, applied in the field of preparation of nevirapine, can solve the problems of only 73% yield, danger, low hydrodechlorination efficiency, etc., and achieve the effects of simple post-processing, reduced risk, and reduced equipment requirements

Inactive Publication Date: 2011-07-20
ZHONGSHAN BAILING BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has obvious disadvantages, such as feeding hydrogen into the autoclave and reacting under the conditions of 50°C and 50atm, which has certain dangers in production, and the yield is only 73%, and the efficiency of hydrogenation dechlorination is low

Method used

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  • Method for preparing nevirapine
  • Method for preparing nevirapine
  • Method for preparing nevirapine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] 1. Preparation of N-(2,6-dichloro-4-methyl-3-pyridyl)-2-chloronicotinamide:

[0033] Add 120.0g of 2-chloro-3-pyridinecarboxylic acid, 650mL of toluene, and 0.5mL of 4-picoline into a 1000mL three-necked flask, and stir at room temperature for 15 minutes under nitrogen protection; cool down to -25°C, and add carbonyldiimidazole in portions 123.6g, during which the temperature was controlled at -20°C to -25°C. After the addition was completed, the reaction was maintained at -20°C to -25°C for 45 minutes; 116.0g of 2,6-dichloro-3-amino-4-methylpyridine was dissolved In 750mL of dry toluene, then drop into the active amide solution in the previous step, maintain -15°C to -20°C during the period, and react at -15°C to -20°C for 2 hours after the addition; after TLC checks that the reaction is complete, add 500mL Stirring with water, the solid precipitated out and was filtered. The solid was washed with 100mL water and 100mL toluene respectively. After vacuum drying, 170.0...

Embodiment 2

[0043] 1. Preparation of N-(2,6-dichloro-4-methyl-3-pyridyl)-2-chloronicotinamide:

[0044] Add 115.0g of 2-chloro-3-pyridinecarboxylic acid, 650mL of toluene, and 0.5mL of 4-picoline into a 1000mL three-necked flask, and stir at room temperature for 15 minutes under nitrogen protection; cool down to -25°C, and add carbonyldiimidazole in portions 118.4g, during which the temperature was controlled at -20°C to -25°C. After the addition was completed, the reaction was maintained at -20°C to -25°C for 45 minutes; 116.0g of 2,6-dichloro-3-amino-4-methylpyridine was dissolved In 750mL of dry toluene, then drop into the active amide solution in the previous step, maintain -15°C to -20°C during the period, and react at -15°C to -20°C for 2 hours after the addition; after TLC checks that the reaction is complete, add 500mL Stirring with water, the solid precipitated out and was filtered. The solid was washed with 100mL water and 100mL toluene respectively. After vacuum drying, 169.2...

Embodiment 3

[0054] 1. Preparation of N-(2,6-dichloro-4-methyl-3-pyridyl)-2-chloronicotinamide:

[0055] Add 125.0g of 2-chloro-3-pyridinecarboxylic acid, 650mL of toluene, and 0.5mL of 4-picoline into a 1000mL three-necked flask, and stir at room temperature for 15 minutes under nitrogen protection; cool down to -25°C, and add carbonyldiimidazole in portions 128.7g, during which the temperature was controlled at -20°C to -25°C. After the addition was completed, the reaction was maintained at -20°C to -25°C for 45 minutes; 116.0g of 2,6-dichloro-3-amino-4-methylpyridine was dissolved In 750mL of dry toluene, then drop into the active amide solution in the previous step, maintain -15°C to -20°C during the period, and react at -15°C to -20°C for 2 hours after the addition; after TLC checks that the reaction is complete, add 500mL Stirring with water, the solid precipitated out and was filtered. The solid was washed with 100mL water and 100mL toluene respectively. After vacuum drying, 169.0...

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Abstract

The invention discloses a method for preparing nevirapine, which comprises the steps of: A. enabling 2-chlorine-3 picolinic acid shown in the structural formula (II) and carbonyl diimidazole to react to produce active amide; B. enabling the active amide produced in the step A to react with 2, 6- dichloro-3-amino-4-methylpyridine shown in the structural formula (I), and producing N-(2, 6-dichloro-4-methyl-3-pyridyl)-2-chlorine niacinamide; C. carrying out nucleophilic substitution reaction on the N-(2, 6-dichloro-4-methyl-3-pyridyl)-2-chlorine niacinamide obtained in the step B and cyclopropylamine, then carrying out cyclization on the obtained products to obtain 2-chloro nevirapine with structure shown in the formula (III); and D. under the presence of catalyst, carrying out hydrogenation reaction on the 2-chloro nevirapine with structure shown in the formula (III) in the step C and non-hydrogen hydrogen source, to obtain the nevirapine with structure shown in the formula (IV). The invention aims at providing a method for preparing the nevirapine, which is low in cost, environment-friendly, higher in safety and suitable for production.

Description

technical field [0001] The invention relates to a method for preparing nevirapine. Background technique [0002] Nevirapine is a non-nucleoside inhibitor of HIV reverse transcriptase, which is used in the treatment of HIV-infected humans. The chemical name is 11-cyclopropyl-5,11-dihydro-4-methyl-6H-pyridyl[3,2-b:2',3'-e][1,4]diazepine- 6-ketone, developed by Boehringer Ingelheim in Germany, was approved by the US FDA in September 1996. The trade name is Viramune, and it is now on the market in many countries. [0003] This product can be combined near the catalytic site of the enzyme, directly acts on reverse transcriptase, inhibits its activity, inhibits HIV replication, and is clinically used to inhibit mother-to-child transmission of AIDS. Nowadays, the formulations of cocktail therapy for AIDS patients all contain nevirapine, and the annual market demand is huge. [0004] There are two main synthetic routes of nevirapine reported at present: Route 1 uses 3-oxo-n-butyr...

Claims

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Application Information

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IPC IPC(8): C07D471/14A61P31/18
Inventor 霍延豪张和平刘遗松黄凌秦和平沈惠宾黄文军周海香梁待亮
Owner ZHONGSHAN BAILING BIOTECHNOLOGY CO LTD
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