Pyrimidine, 2-amino-4-chloro-5-fluoro- (7CI,8CI) synthesis

Yield: 26%

Reaction Conditions:

with ammonium hydroxide in tetrahydrofuran at 0;Green chemistry;Temperature;

Steps:

1.1; 1.2; 1.3; 2.1; 2.2; 2.3; 3.1; 3.2; 3.3
(1) Take 100g of 2,4-dichloro-5-fluoropyrimidine and dissolve it in 1000 ml of anhydrous tetrahydrofuran, lower it to a low temperature of 0 ° C, and add ammonia water dropwise. The speed of ammonia water drop control should be kept at When the temperature exceeds 0 , keep the temperature at 0 for 2 to 3 hours.(2) Naturally rise to room temperature for 1-2 hours, evaporate the solvent, dissolve in ethyl acetate, wash with saturated aqueous sodium bicarbonate solution, wash with saturated brine, dry, filter, and concentrate to obtain 2-chloro-4-amino-5-fluoropyrimidine And 2-amino-4-chloro-5-fluoropyrimidine 88 g;(3) The mixture obtained in step (2) is subjected to column chromatography to obtain 23.44 g of 2-amino-4-chloro-5-fluoropyrimidine, the purity is greater than 98%, and the yield is 26%.

References:

Nanjing Puruida Pharmaceutical Technology Co., Ltd.;Wang Xiaobo CN110343074, 2019, A Location in patent:Paragraph 0005; 0012-0014