Reaction Steps
N-(3′-Fluoro-5,6′-dimethyl-2,2′-bipyridin-4-yl)-1H-pyrazolo[4,3-b]pyridin-7-amine (374 mg, 1.119 mmol) and Cs2CO3 (364 mg, 1.119 mmol) were stirred in DMF (6 mL) for 10 minutes. 2-Methyloxirane (0.079 mL, 1.119 mmol) was added, the vessel sealed and the mixture was heated in a microwave at 120° C. for 30 minutes. The reaction mixture was cooled and purified by preparative HPLC using a Sunfire Prep 5 μm C18, 75×30 mm column eluting with a gradient of 10-25% acetonitrile (containing 0.035% TFA) in water (containing 0.05% TFA) to separate the regioisomers which in turn were further purified using a Chiralcel AD-H (5 um, 20×150 mm) column eluting with CO2: 15% EtOH+0.1% DEA at 50 mL/min to give (S)-1-(7-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.21 (d, J=4 Hz, 3H) 2.44 (s, 3H) 2.56 (s, 3H) 4.20-4.33 (m, 1H) 4.37 (dd, J=12, 8 Hz, 1H) 4.49 (dd, J=16, 4 Hz, 1H) 6.99 (d, J=4 Hz, 1H) 7.35 (dd, J=8, 4 Hz, 1H) 7.60 (dd, J=12, 8 Hz, 1H) 7.92 (s, 1H) 8.28 (d, J=4 Hz, 1H) 8.37 (s, 1H) 8.49 (s, 1H), MS [M+H] found 393.4; (R)-1-(7-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-ylamino)-2H-pyrazolo[4,3-b]pyridin-2-yl)propan-2-ol 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.22 (d, J=4 Hz, 3H) 2.46 (s, 3H) 2.57 (s, 3H) 4.21-4.34 (m, 1H) 4.39 (dd, J=12, 8 Hz, 1H) 4.51 (dd, J=12, 4 Hz, 1H) 7.01 (d, J=4 Hz, 1H) 7.36 (dd, J=8, 4 Hz, 1H) 7.61 (dd, J=8, 4 Hz, 1H) 7.93 (s, 1H) 8.29 (d, J=4 Hz, 1H) 8.38 (s, 1H) 8.50 (s, 1H), MS [M+H] found 393.4; (R)-1-(7-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-ylamino)-1H-pyrazolo[4,3-b]pyridin-1-yl)propan-2-ol 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.22 (d, J=8 Hz, 3H) 2.46 (s, 3H) 2.58 (s, 3H) 4.14-4.34 (m, 1H) 4.34-4.43 (m, 1H) 4.51 (m, 1H) 7.01 (d, J=4 Hz, 1H) 7.37 (dd, J=8, 4 Hz, 1H) 7.61 (dd, J=12, 12 Hz, 1H) 7.94 (s, 1H) 8.29 (d, J=4 Hz, 1H) 8.39 (s, 1H) 8.50 (s, 1H), MS [M+H] found 393.4; and (S)-1-(7-(3′-fluoro-5,6′-dimethyl-2,2′-bipyridin-4-ylamino)-1H-pyrazolo[4,3-b]pyridin-1-yl)propan-2-ol 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.21 (d, J=8 Hz, 3H) 2.46 (s, 3H) 2.57 (s, 3H) 4.19-4.34 (m, 1H) 4.38 (m, 1H) 4.50 (m, 1H) 7.00 (d, J=4 Hz, 1H) 7.36 (dd, J=8, 4 Hz, 1H) 7.61 (dd, J=8, 8 Hz, 1H) 7.93 (s, 1H) 8.29 (d, J=4 Hz, 1H) 8.38 (s, 1H) 8.50 (s, 1H), MS [M+H] found 393.4.
