20980-22-7

110-85-0

1722-12-9

20980-22-7

Generic method: 2-chloro-4,6-disubstituted pyrimidines (17) were prepared by reaction of the diazonium salt of 4,6-disubstituted pyrimidin-2-amine (16) with concentrated hydrochloric acid and ZnCl?[35]. Compound 18 was synthesized with reference to the method of literature [32] with modifications. To a stirred solution of piperazine (45 mmol) and K?CO? (16.5 mmol) in water (20 mL) was added 2-chloro-4,6-disubstituted pyrimidine (17) (18 mmol) in batches at 50-65 °C. The reaction mixture was stirred at 60-65 °C for 1 hour and subsequently cooled to 35 °C. The solid by-product 1,4-bispyrimidinylpiperazine was removed by filtration, the filtrate was extracted three times with chloroform, the organic phase was dried with Na?SO? and concentrated under reduced pressure to give compound 18, which could be used in the subsequent reaction without further purification.18a: yellow oil, 88% yield.