3-{6-[2-(2-Chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyridin-3-yl}-azetidine-1-carboxylic acid tert-butyl ester → 2-[4-(5-Azetidin-3-yl-pyridin-2-ylamino)-7-fluoropyrazolo[4,3-c]pyridin-2-yl]-3-chlorobenzonitrile hydrochloride salt

Participants

Reaction Steps

To a round bottomed flask containing 3-{6-[2-(2-chloro-6-cyanophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyridin-3-yl}-azetidine-1-carboxylic acid tert-butyl ester (98 mg, 0.19 mmol), was added a solution of HCl (1.25 N in propan-2-ol, 10 mL) and the suspension was stirred at room temperature for 16 hours and then heated at 50° C. for 4 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure and the resultant solid was triturated with diethyl ether, filtered and dried. The crude residue obtained was purified by HPLC [gradient: 20 to 98% MeOH (0.1% NH4OH) in water (0.1% NH4OH)] and freeze dried to afford the free base of the title compound which was dissolved in a solution of HCl (1.25 N in propan-2-ol, 5.0 mL), stirred for 4 hours and was then concentrated under reduced pressure. The resultant residue was triturated with diethyl ether, filtered and dried to yield the title compound as a white solid (30 mg, 35% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.00 (d, J=2.5 Hz, 1H), 8.50 (d, J=2.5 Hz, 1H), 8.31 (dd, J=8.7, 2.5 Hz, 1H), 8.26-8.22 (m, 2H), 8.18 (d, J=4.9 Hz, 1H), 7.96 (t, J=8.1 Hz, 1H), 7.75 (d, J=8.9, 1H), 4.39-4.28 (m, 3H), 4.24-4.14 (m, 2H). LCMS (Method B): RT=2.29 min, m/z: 420 [M+H+].

Provenance & Evidence