Formic Acid → HCID 86684742, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-[4-[2-[[(3R,3aR,6R,6aR)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl]oxy]-6-chloro-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-5-yl]phenyl]benzonitrile (49.4 mg, 0.082 mmol), formic acid (1.0 mL, 26.1 mmol), and saturated aqueous KHSO4 (0.06 mL) was heated to 40° C. with stirring. After 6.5 hours, the reaction mixture was cooled to room temperature and placed in the refrigerator overnight, and then cooled to 0° C. in an ice bath. The pH was adjusted to pH 14 through the addition of 5 N NaOH (5.2 mL, 26 mmol). THF (2 mL) was added to the reaction mixture, which was removed from the ice bath and allowed to warm to room temperature. After stirring for 45 minutes at room temperature, the pH was adjusted to 7 through the addition of 2 N HCl. The reaction mixture was partitioned between EtOAc (30 mL) and water (30 mL). The aqueous layer was extracted with EtOAc (2×20 mL). The organic layers were combined, washed with brine (1×20 mL), dried over Na2SO4, filtered, and evaporated under reduced pressure to give a pale yellow solid. Purification 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 afforded the title compound as a white solid following lyophilization from ethanol and benzene. LC-MS: calculated for: C25H19ClN4O4 474.11 observed m/e: 475.12 (M+H)+ (Rt 1.15/2 min).

Provenance & Evidence