Method for synthesizing pyrazolo[3,4-d]pyrimidine derivative by two steps

A technology of pyrimidine derivatives and synthesis methods, which is applied in the field of two-step synthesis of pyrazolo[3,4-d]pyrimidine derivatives, can solve the problems of large solvent consumption, difficult product purification, and low overall yield, etc. To achieve the effect of improving the level of cleaning

Inactive Publication Date: 2011-07-06
广德宏霞科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
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Problems solved by technology

The traditional synthesis method uses ethoxymethylenemalononitrile and phenylhydrazine derivatives as raw materials, not only the reaction steps are long, the total yield is not high, and at the same time, due to the influence of isomers, the product purification is difficult, and column Separation technology, complex operation, large solvent consumption, and a large amount of waste liquid that is difficult to handle

Method used

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  • Method for synthesizing pyrazolo[3,4-d]pyrimidine derivative by two steps

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Step 1: Add 50ml of tetrahydrofuran and 5mmol of p-nitrophenylhydrazine to a 100ml three-necked flask, add 5mmol of triethylamine at the same time, stir at room temperature for 0.5h, then slowly add 5mmol of 4,6-dichloropyrimidine-5 under nitrogen protection - Formaldehyde, TLC tracking (developer V 丙酮 :V 石油醚 =1:2), after about 2 hours, the reaction is over, filter to remove insoluble matter, distill the filtrate to 20ml under reduced pressure, put it in the refrigerator overnight, and crystallize to obtain a yellow solid as the condensation product M (ie: 5-((2-(4 -nitrophenyl) hydrazino) methyl) -4,6-dichloropyrimidine), yield 85%.

[0019] Step 2: Add 50ml tetrahydrofuran to a 100ml three-necked flask, add the above-mentioned condensation product M, stir to dissolve, add 10mmol triethylamine, continue stirring at room temperature for 30h, distill under reduced pressure to concentrate the solution to 10ml, add 20ml water, there are a lot of solids Precipitate, filte...

Embodiment 2

[0021] Step 1: Add 50ml of tetrahydrofuran and 5mmol of p-nitrophenylhydrazine to a 100ml three-necked flask, add 6mmol of triethylamine at the same time, stir at room temperature for 0.5h, then slowly add 6mmol of 4,6-dichloropyrimidine-5 under nitrogen protection - Formaldehyde, TLC tracking (developer V 丙酮 :V 石油醚 =1:2), after about 2.5 hours, the reaction is over, filter to remove insoluble matter, distill the filtrate to 20ml under reduced pressure, put it in the refrigerator overnight, and crystallize to obtain a yellow solid as the condensation product M (ie: 5-((2-( 4-nitrophenyl) hydrazino) methyl) -4,6-dichloropyrimidine), the yield was 90%.

[0022] Step 2: Add 50ml tetrahydrofuran to a 100ml three-necked flask, add the above-mentioned condensation product M, stir to dissolve, add 12mmol triethylamine, continue stirring at room temperature for 30h, distill under reduced pressure to concentrate the solution to 10ml, add 20ml water, there are a lot of solids Precipit...

Embodiment 3

[0024] Step 1: Add 50ml of tetrahydrofuran and 5mmol of p-nitrophenylhydrazine hydrochloride into a 100ml three-necked flask, and at the same time add 11mmol of triethylamine, stir at room temperature for 0.5h, then slowly add 5mmol of 4,6-dichloro Pyrimidine-5-carbaldehyde, TLC tracking (developer V 丙酮 :V 石油醚 =1:2), after about 3 hours, the reaction is over, the insoluble matter is removed by filtration, the filtrate is distilled under reduced pressure to 20ml, put in the refrigerator to freeze overnight, and a yellow solid is crystallized to obtain the condensation product M (ie: 5-((2-(4 -nitrophenyl) hydrazino) methyl) -4,6-dichloropyrimidine), yield 86%.

[0025] Step 2: Add 50ml tetrahydrofuran to a 100ml three-necked flask, add the above-mentioned condensation product M, stir to dissolve, add 8mmol triethylamine, continue stirring at room temperature for 27h, distill under reduced pressure to concentrate the solution to 10ml, add 20ml water, there are a lot of solids ...

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Abstract

The invention relates to the field of organic synthesis, in particular to a method for synthesizing a pyrazolo[3,4-d] pyrimidine derivative by two steps, which is used for synthesizing 1-(4-nitrobenzophenone)-4-chlorine-1H-pyrazolo[3,4-d] pyrimidine by two-step operation. The method comprises the following steps of: condensing 4-nitrophenyl hydrazine and 4,6-dichloropyrimidine-5-formaldehyde in the presence of triethylamine by taking tetrahydrofuran as a solvent to obtain a condensation product, and separating and purifying the condensation product; and dissolving the condensation product with tetrahydrofuran, adding an appropriate amount of triethylamine, fully undergoing a reaction at a room temperature, evaporating most solvent after the reaction, adding water until a yellow crude product solid is separated out, and recrystallizing the filtered solid with methanol to obtain the 1-(4-nitrobenzophenone)-4-chlorine-1H-pyrazolo[3,4-d] pyrimidine, wherein the product content is more than or equal to 98 percent, and the total yield is over 75 percent. The two steps of reactions are performed at the room temperature without column separation, so that the clean level of a synthesis technology is raised.

Description

technical field [0001] The present invention relates to the field of organic synthesis, in particular to a two-step synthesis method for pyrazolo[3,4-d]pyrimidine derivatives, namely the synthesis of 1-(4-nitrophenyl)-4-chloro-1H-pyrazole A new method for [3,4-d]pyrimidine, using 4-nitrophenylhydrazine and 4,6-dichloropyrimidine-5-carbaldehyde as raw materials, through two-step operations, first synthesized to obtain 5-((2-( 4-nitrophenyl) hydrazino) methyl) -4,6-dichloropyrimidine, and then synthesize 1-(4-nitrophenyl)-4-chloro-1H-pyrazolo[3,4- d] pyrimidine. Background technique [0002] As the structural units of important biomolecules DNA and ATP, pyrazolopyrimidine derivatives have a wide range of biological activities and are the dominant structures in the design of new drugs, which have always been highly valued by medicinal chemists. At present, many anticancer drugs have been developed based on 1H-pyrazolo[3,4-d]pyrimidine and other pyrimidine derivatives, which a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04
Inventor 孟启江昆陈海浪周长青孙小强
Owner 广德宏霞科技发展有限公司
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