2-amino, 2-methyl cyanoacetate/ethyl cyanoacetate, 2-amino, 2-cyanoacetic acid and synthesis process thereof

Abstract

The invention discloses a synthesis process of 2-amino, 2-methyl cyanoacetate / ethyl cyanoacetate. The synthesis process comprises the following step: carrying out pressurized catalytic hydrogenation reaction on liquid 2-nitroso and 2-methyl cyanoacetate / ethyl cyanoacetate to generate the 2-amino, 2-methyl cyanoacetate / ethyl cyanoacetate. Wherein the liquid 2-nitroso and 2-methyl cyanoacetate / ethyl cyanoacetate are generated by carrying out nitrosation reaction on methyl cyanoacetate / ethyl cyanoacetate and sodium nitrite. The 2-amino, 2-methyl cyanoacetate / ethyl cyanoacetate can be used as an intermediate in the synthesis process of 2, 4, 5-triamino-6-hydroxypyrimidine, and can be directly subjected to ring closing with guanidyl to generate 2, 4, 5-triamino-6-hydroxypyrimidine, so that the problems of high water consumption and high wastewater yield in the synthesis process can be solved, and great economic significance and environmental protection significance are achieved. In addition, the invention further develops the application of the intermediate, and the intermediate can be used for synthesizing 2, 4, 5-triamino-6-hydroxypyrimidine and guanidyl to generate 2, 4, 5-triamino-6-hydroxypyrimidine, and can also be used for synthesizing 2-amino and 2-cyanoacetic acid.

Description

technical field

[0001] The invention relates to the field of pharmacy, in particular to methyl / ethyl 2-amino, 2-cyanoacetate, 2-amino, 2-cyanoacetic acid and a synthesis process thereof. Background technique

[0002] 2,4,5-Triamino-6-hydroxypyrimidine is an important intermediate of vitamin folic acid and a series of high-efficiency and low-toxic antiviral drugs such as acyclovir and famciclovir.

[0003] At present, 2,4,5-triamino-6-hydroxypyrimidine has been using the traditional synthetic route:

[0004] (1) guanidine hydrochloride / guanidine nitrate+sodium methylate / methanol=free guanidine+methanol solution;

[0005] (2) free guanidine+methyl cyanoacetate / ethyl cyanoacetate=2,4-diamino-6-hydroxypyrimidine;

[0006] (3) 2,4-diamino-6-hydroxypyrimidine+sodium nitrite=2,4-diamino-5-nitroso-6-hydroxypyrimidine;

[0007] (4) 2,4-diamino-5-nitroso-6-hydroxypyrimidine+H 2 (Catalyst) = 2,4,5-triamino-6-hydroxypyrimidine.

[0008] But the synthetic route of above-mentioned 2,...