2-Acetylamino-4-aminotoluene → N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-methylphenyl]acetamide

온도

150 °C

in microwave tube was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (400 mg, 1.71 mmol), N-(5-amino-2-methylphenyl)acetamide (281 mg, 1.71 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (99 mg, 0.17 mmol) in DMA (0.5 mL).Pd2(dba)3 (78 mg, 0.09 mmol) and cesium carbonate (1116 mg, 3.42 mmol) were added. degassed, filled with N2.capped. then microwave 150C for 30 min. The reaction was divided by 4, run 100mg scale four time. combined all of crude mixture, filtered and washed with MeOH. the organic solvent was removed. The black residue was tried to purifed by ISCO. impurity and prod came out together too quickly. purified by glass-clumn (150g silica, Hex to EtOAc:Hex =1:1 to EtOAc), colleceted product fraction. concentrated to give offwhite solid. LCMS showed about 10% impurity. The solid was washed with hot EtOAc(5 mL), filtered. The solild was washed with water (1mL) and EtOAc(1 mL) to give about 110mg white solid. LCMS and NMR are OK, see attachment. low yield was due to hot EtOAc wash, lost some prod.

ORD 기록

ord-56f044d6c15d456091eeeb1952199469

출처 데이터셋

750 AstraZeneca ELN dataset

원본 링크

출처 보기