Reaction Steps
A mixture of (3R,3aR,6R,6aR)-6-[6-chloro-5-[4-[5-[4-(2-hydroxy-2-methyl-propyl)pyrazol-1-yl]-2-pyridyl]phenyl]-1-(2-trimethylsilylethoxy-methyl)imidazo[4,5-b]pyridin-2-yl]oxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol (10.1 mg, 0.014 mmol), formic acid (1.0 mL, 26.1 mmol), and saturated aqueous KHSO4 (0.05 mL) was heated to 40° C. with stirring. After 16 hours, the reaction mixture was cooled to room temperature before being cooled to 0° C. in an ice bath. The pH of the reaction mixture was adjusted to pH 14 through the addition of 5 N NaOH (5.8 mL, 29.0 mmol). THF (2 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 7 through the addition of 2 N HCl. The reaction mixture was partitioned between EtOAc (30 mL) and water (20 mL). The aqueous layer was extracted with EtOAc (2×20 mL). The organic layers were combined, washed with brine (1× mL), dried over MgSO4, filtered, and evaporated under reduced pressure to give a white residue. This material was dissolved in DMSO/MeOH, and purified by HPLC reverse phase (C-18), using a 30×150 mm Sunfire™ column and eluting with a 20%-100% acetonitrile/water+0.05% TFA gradient followed by a 100% acetonitrile+0.05% TFA flush. The desired fractions were combined, evaporated under reduced pressure, and lyophilized from ethanol and benzene to afford the title compound as a pale yellow solid. LC-MS: calculated for C30H29ClN6O5 589.19 observed m/e: 589.28 (M+H)+ (Rt 1.10/2 min); 1H NMR δ (ppm) (CD3OD): 9.15 (d, J=2.5 Hz, 1H), 8.46 (dd, J=2.7 Hz, 8.9 Hz, 1H), 8.26 (s, 1H), 8.19 (d, J=8.7 Hz, 1H), 8.14 (d, J=8.4 Hz, 2H), 7.97 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.73 (s, 1H), 5.58 (qt, J=5.2 Hz, 1H), 4.98 (t, J=5.2 Hz, 11H), 4.47 (t, J=5.0 Hz, 1H), 4.27-4.31 (m, 1H), 4.17 (dd, J=5.4 Hz, 10.2 Hz, 1H), 4.14 (dd, J=4.7 Hz, 10.2 Hz, 1H), 3.91 (m, 1H), 3.60 (t, J=8.6 Hz, 1H), 2.73 (s, 2H), 1.25 (s, 6H).
