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3-bromopyrazol[1,5-alpha]pyrimidine-2-formic acid synthesis process

A technology for the synthesis of bromopyrazoline and its application in the field of practical synthesis of 3-bromopyrazoline [1,5-α] pyrimidine-2-carboxylic acid, achieving easy scale-up, readily available raw materials, and high overall yield Effect

Inactive Publication Date: 2013-05-01
SUZHOU KANGRUN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In order to overcome the shortcoming of existing synthetic method, the object of the present invention is to provide the synthetic technique of 3-bromopyrazoline [1,5-α] pyrimidine-2-carboxylic acid

Method used

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  • 3-bromopyrazol[1,5-alpha]pyrimidine-2-formic acid synthesis process
  • 3-bromopyrazol[1,5-alpha]pyrimidine-2-formic acid synthesis process

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Embodiment

[0015] The first step: the synthesis of pyrazoline [1,5-α] pyrimidine-2-ethyl carboxylate

[0016] 1,1,4,4-Tetramethoxypropane (10.5 g, 64.5 mmol) was added to 5-amino-pyrazole-3-carboxylic acid ethyl ester (10 g, 64.5 mmol) in 2 M aqueous hydrochloric acid at 70 °C ( 120 mL), the mixture was stirred at this temperature for 10 minutes and then cooled. Add saturated sodium bicarbonate aqueous solution to pH = 8, and extract the solution with ethyl acetate. The organic phase is dried with anhydrous sodium sulfate and then spin-dried. The residue is subjected to column chromatography to obtain pyrazoline [1,5-α] pyrimidine - Ethyl 2-carboxylate (4.4 g, 34%).

[0017] 1 HNMR (400MHz, CDCl 3 ): 1.45(t,3H), 4.50(m,2H), 6.95(m,1H), 7.25(s,12H), 8.57(m,1H), 8.76(m,1H).

[0018] The second step: the synthesis of ethyl 3-bromopyrazoline[1,5-α]pyrimidine-2-carboxylate

[0019] The mixture of pyrazoline[1,5-α]pyrimidine-2-carboxylate (1g, 5.24mmol), NBS (0.93g, 5.24mmol) and DMF (10m...

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Abstract

The present invention relates to 3-bromopyrazol[1,5-alpha]pyrimidine-2-formic acid synthesis process, which is characterized in that ethyl 5-amino-1H-pyrazole-3-carboxylate is adopted as a raw material, and is subjected to condensation with 1,1,3,3-tetramethoxypropane to obtain pyrazol[1,5-alpha]pyrimidine-2-acid ethyl ester, the pyrazol[1,5-alpha]pyrimidine-2-acid ethyl ester reacts with NBS to obtain 3-bromopyrazol[1,5-alpha]pyrimidine-2-acid ethyl ester, and the 3-bromopyrazol[1,5-alpha]pyrimidine-2-acid ethyl ester is subjected to hydrolysis in a sodium hydroxide aqueous solution to obtain the 3-bromopyrazol[1,5-alpha]pyrimidine-2-formic acid. The synthesis process has characteristics of simple synthesis route, reasonable process selection, low raw material cost, easily available raw materials, simple operation and post-treatment, high total yield, no use of highly toxic reagents, easy amplification and capability of large scale production. With the synthesis process, disadvantages of expensive and difficultly-obtained raw materials, low yield, requirement of a microwave condition, complex operation, difficult operation, difficult amplification and the like in the processes in the existing literature are solved.

Description

technical field [0001] The invention relates to a practical synthesis method of 3-bromopyrazoline [1,5-α] pyrimidine-2-carboxylic acid. Background technique [0002] 3-Bromopyrazolin[1,5-α]pyrimidine-2-carboxylic acid is a key intermediate in the synthesis of 3-bromopyrazolin[1,5-α]pyrimidine-2-amine, which can be obtained in triethyl Reaction with diphenylphosphorylazide (DPPA) in the presence of amine followed by removal of Boc (tertiary oxygen carbonyl) by acid treatment yields 3-bromopyrazolin[1,5-α]pyrimidin-2-amine. Various amides can be generated by coupling the amino group of 3-bromopyrazolin[1,5-α]pyrimidin-2-amine with various carboxylic acids, and these amides have high potassium ion mediating activity , can regulate the quantity and rate of potassium ions passing through the cell membrane (US2012122888A1). The bromine atom at the 3 position is also a highly active reaction site, which can undergo transition metal-catalyzed coupling reactions with some fragments...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04
Inventor 徐卫良左兵徐炜政
Owner SUZHOU KANGRUN PHARMA