Preparation method of 4-chloropyrrolo[2,3-d]pyrimidine

A technology of chloropyrrolopyrimidine and hydroxypyrrolopyrimidine, which is applied in the field of chemical synthesis, can solve the problems of 4-chloropyrrolopyrimidine, such as unsafe hazards, and achieve the effects of reduced synthesis cost, safe and reliable synthesis process, and short production cycle

Inactive Publication Date: 2010-09-15
兰州五龙新能源科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the use of highly dangerous sodium hydride as a raw material in this document has brought unsafe hidden dangers to the synthesis of 4-chloropyrrolopyrimidine

Method used

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  • Preparation method of 4-chloropyrrolo[2,3-d]pyrimidine
  • Preparation method of 4-chloropyrrolo[2,3-d]pyrimidine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] (1) Synthesis of 2-mercapto, 4-amino, 6-hydroxypyrimidine

[0041] Dissolve ethyl cyanoacetate and thiourea in ethanol at a molar ratio of 1:1, slowly add sodium ethoxide that is 1.5 times the molar weight of ethyl cyanoacetate at 0°C, stir at room temperature for 2 hours, then raise the temperature to 85°C, and reflux the reaction After 8 hours, cool to room temperature, filter, wash the solid with ethanol, and dry to obtain 2-mercapto, 4-amino, 6-hydroxypyrimidine in a yield of 85%.

[0042] (2) Synthesis of 4-amino, 6-hydroxypyrimidine

[0043] Add 2-mercapto, 4-amino, and 6-hydroxypyrimidine to ammonia water with a mass concentration of 25%, and the amount of ammonia is 10 times the mass of 2-mercapto, 4-amino, and 6-hydroxypyrimidine; then add 2-mercapto , 4-amino, active nickel with 3 times the molar weight of 6-hydroxypyrimidine, heated to 80 ° C, refluxed for 6 hours, then filtered while hot to remove active nickel, cooled to room temperature, precipitated soli...

Embodiment 2

[0050] (1) Synthesis of 2-mercapto, 4-amino, 6-hydroxypyrimidine

[0051] Dissolve ethyl cyanoacetate and thiourea in ethanol at a molar ratio of 1:3, slowly add sodium ethoxide that is twice the molar amount of ethyl cyanoacetate at 5°C, stir at room temperature for 3 hours, then raise the temperature to 90°C, and reflux the reaction After 9 hours, cool to room temperature, filter, wash the solid with ethanol, and dry to obtain 2-mercapto, 4-amino, 6-hydroxypyrimidine in a yield of 80%.

[0052] (2) Synthesis of 4-amino, 6-hydroxypyrimidine

[0053] Add 2-mercapto, 4-amino, and 6-hydroxypyrimidine to ammonia water with a mass concentration of 20%, and the amount of ammonia is 15 times the mass of 2-mercapto, 4-amino, and 6-hydroxypyrimidine; then add 2-mercapto , 4-amino, 6-hydroxypyrimidine mole to that 4 times the active nickel, heated to 80 ° C, refluxed for 6 hours, then filtered to remove the active nickel while hot, cooled to room temperature, precipitated solid, filte...

Embodiment 3

[0060] (1) Synthesis of 2-mercapto, 4-amino, 6-hydroxypyrimidine

[0061] Dissolve ethyl cyanoacetate and thiourea in ethanol at a molar ratio of 1:2, slowly add sodium ethoxide that is 2.5 times the molar weight of ethyl cyanoacetate at 0°C, stir at room temperature for 1.5 hours, then raise the temperature to 90°C, and reflux the reaction After 10 hours, cool to room temperature, filter, wash the solid with ethanol, and dry to obtain 2-mercapto, 4-amino, 6-hydroxypyrimidine in a yield of 82%.

[0062] (2) Synthesis of 4-amino, 6-hydroxypyrimidine

[0063] 2-mercapto, 4-amino, and 6-hydroxypyrimidine are added to ammonia water with a mass concentration of 25%, and the amount of ammonia is 20 times the mass of 2-mercapto, 4-amino, and 6-hydroxypyrimidine; then add 2-mercapto , 4-amino, 6-hydroxypyrimidine mole to that 6 times the active nickel, heated to 80 ° C, refluxed for 6 hours, then filtered while hot to remove active nickel, cooled to room temperature, precipitated sol...

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Abstract

The invention provides a novel method for synthesizing 4-chloropyrrolo[2,3-d]pyrimidine, belonging to the technical field of chemical synthesis. The method comprises the steps of carrying out four-step reaction by using ethyl cyanoacetate, thiourea, caustic alcohol, 2-chloroacetaldehyde and sodium acetate as raw materials and using alcohol, ammonia water, water and phosphorus oxychloride as solvents as well as using active nickel as a catalyst to obtain the 4-chloropyrrolo[2,3-d]pyrimidine as a target product; and carrying out data representation by liquid chromatogram, nuclear magnetism spectrogram and mass spectrum. The invention has short process route and production cycle, low synthesis cost, safe and reliable synthesis and simple and convenient posttreatment method, and avoids the use of dangerous goods of sodium hydride. The product prepared by the method has high yield (50-58 percent) and high purity (98-99 percent).

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis and relates to a preparation method of 4-chloropyrrolopyrimidine. Background technique [0002] 4-Chloropyrrolopyrimidine is an important pharmaceutical intermediate, which is the core intermediate of many drugs including CP690550, CGP76030, etc., and is widely used in the synthesis of many pharmaceutical intermediates at home and abroad, and has great potential market. [0003] "Chemical Reagents" 2007 Issue 05 disclosed a synthetic method of 4-chloropyrrolopyrimidine, which uses ethyl cyanoacetate as the starting material, and bromoacetaldehyde diethyl acetal to obtain α-cyano group under the action of sodium hydride α-(2,2-diethoxyethyl)ethyl acetate, and then ring-closed with thiourea, followed by elimination of mercapto groups under nickel catalysis, hydrolysis under acidic conditions, and finally replaced by phosphorus oxychloride to obtain 4-chloro pyrrolopyrimidine. The total...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04
Inventor 陈林张艳
Owner 兰州五龙新能源科技有限公司
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