Reaction Steps
A mixture of formic acid (6 mL, 156 mmol), saturated aqueous KHSO4 (0.66 mL, 2.58 mmol), and (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-(6-pyrazol-1-yl-3-pyridyl)phenyl]-1-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydro-furo[3,2-b]furan-3-ol (1.67 g, 2.58 mmol) was stirred at 60° C. overnight, and then cooled to 0° C. in an ice bath. The pH of the reaction mixture was adjusted to pH>11 through the addition of NaOH (6.24 g, 156 mmol) in water (5 mL). THF (10 mL) was added to the reaction mixture, and the reaction was removed from the ice bath and allowed to warm to room temperature. After 30 minutes, the pH of the reaction mixture was adjusted to pH 6 through the addition of concentrated HCl. The biphasic mixture was separated. The organic layer and the resulting white precipitate were concentrated under reduced pressure, redissolved in DMSO, and filtered before being purified by preparative HPLC Reverse phase (C-18), using a 19×100 mm Sunfire™ column and eluting with a 10%-90% acetonitrile/water+0.05% TFA gradient followed by a 90% acetonitrile/water+0.05% TFA flush. The desired fractions were combined, and evaporated under reduced pressure. The resulting residue was washed with MeOH and lyophilized from acetonitrile and water to afford the title compound as a white solid. LC-MS: calculated for C26H21ClN6O4 516.13 observed m/e: 517.22 (M+H)+ (Rt 1.16/2 min); 1H NMR δ (ppm) (CD3OD): 8.80 (d, J=2.5 Hz, 1H), 8.67 (d, J=2.0 Hz, 1H), 8.30 (dd, J=2.8 Hz, 8.5 Hz, 1H), 8.06 (d, J=9.0 Hz, 1H), 7.81-7.83 (m, 6H), 6.84 (t, J=2.3 Hz, 1H), 5.56 (qt, J=55 Hz, 1H), 4.99 (t, J=5.3 Hz, 1H), 4.49 (t, J=5.0 Hz, 1H), 4.28-4.32 (m, 1H), 4.19 (dd, J=6.0 Hz, 10 Hz, 1H), 4.13 (dd, J=4.8 Hz, 10.3 Hz, 1H), 3.92 (dd, J=7.0 Hz, J=8.0 Hz, 1H), 3.62 (t, J=8.5 Hz, 1H).
