N,N-Dimethylpiperidin-4-amine → Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [4-(5-chloro-2-difluoromethoxy-phenyl)-2-(4-dimethylamino-piperidin-1-yl)-thiazol-5-yl]-amide

Participants

Reaction Conditions

Reaction Steps

Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [2-bromo-4-(5-chloro-2-difluoromethoxy-phenyl)-thiazol-5-yl]-amide (100 mg, 0.2 mmol) and 4-dimethylaminopiperidine (128 mg, 1 mmol) were dissolved in DMA (1 ml) and heated in a microwave at 160° C. for 1 hour. The residue was dissolved in MeOH and loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH. The resulting yellow glass was purified by MDAP (Method 1). Appropriate fractions were combined and evaporated to afford a yellow solid. The residue was dissolved in MeOH and loaded onto an SCX-2 cartridge which had been conditioned with MeOH. After flushing with MeOH, the product was eluted with 2M ammonia in MeOH to give the title compound as a yellow-orange solid (43 mg, 39%). LCMS (Method 5) [M+H]+=548.1, RT=3.20 min. 1H NMR (400 MHz, DMSO-d6) δ: (ppm) 10.23 (s, 1H), 9.36 (dd, 1H, J=1.6, 7.0 Hz), 8.68 (s, 1H), 8.63 (dd, 1H, J=1.6, 4.2 Hz), 7.66 (d, 1H, J=2.7 Hz), 7.59 (dd, 1H, J=2.6, 8.8 Hz), 7.41 (d, 1H, J=9.0 Hz), 7.31 (dd, 1H, J=4.2, 6.7 Hz), 7.18 (t, 1H, J=73.5 Hz), 3.93 (d, 2H, J=12.7 Hz), 3.02 (dd, 2H, J=10.3, 12.3 Hz), 3.05-2.95 (m, 1H), 2.40-2.26 (m, 6H), 1.92-1.89 (m, 2H), 1.58-1.47 (m, 2H).

Provenance & Evidence