Reaction Steps
To a solution of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-oxo-2-(4-oxo-1-piperidyl)ethyl]pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (201.7 mg 0.38 mmol) in dichloromethane (1.0 mL) was added acetic acid (0.3 mL, 5.24 mmol). To this was then added 1-(aminomethyl)cyclopropanecarbonitrile (47.2 mg, 0.466 mmol). This was then stirred at room temperature for 5 minutes. The reaction was then cooled to 0° C. and to this was added sodium triacetyoxyborohydride (124.1 mg, 0.56 mmol) and stirred for 3 hours and let warm to room temperature in the process. LC/MS (method 31) shows product as a major peak. The reaction was quenched by adding 2 mL water followed by 10 mL saturated sodium bicarbonate solution. This was the extracted with dichloromethane and the organic layers were dried with solid anhydrous magnesium sulfate powder, filtered and concentrated to give a white solid. 20.6 mg was then purified by reverse phase HPLC purification to afford 10.2 mg of N-(3-(5-chloro-2-(difluoromethoxy)phenyl)-1-(2-(4-(((1-cyanocyclopropyl)methyl)amino)piperidin-1-yl)-2-oxoethyl)-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LC/MS (method 38) [M+H]+=624.2, RT=2.80 min. 1H NMR (400 MHz, DMSO-d6) 9.75 (s, 1H), 9.34 (dd, J=7.0, 1.7 Hz, 1H), 8.68 (dd, J=4.3, 1.6 Hz, 1H), 8.67 (s, 1H), 8.30 (s, 1H), 7.63 (dd, J=8.8, 2.7 Hz, 1H), 7.56 (d, J=2.7 Hz, 1H), 7.46 (d, J=8.8 Hz, 1H), 7.29 (dd, J=7.0, 4.2 Hz, 1H), 7.25 (t, J=73.0 Hz, 1H), 5.23 (d, J=4.7 Hz, 2H), 4.12 (d, J=12.7 Hz, 1H), 3.84 (d, J=13.7 Hz, 1H), 3.14 (t, J=11.9 Hz, 1H), 2.85 (t, J=11.9 Hz, 1H), 2.71-2.65 (m, 3H), 2.02 (s, 1H), 1.83 (t, J=16.2 Hz, 2H), 1.33-1.12 (m, 4H), 0.94 (m, 2H).
