Sodium borohydride → N-(4-(3-fluoro-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide

Participants

Reaction Steps

To solution of CaCl2 (0.188 g, 1.70 mmol) in 1.3 mL water was added a slurry of diethyl 2-acetamido-2-(2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethyl)malonate (0.400 g, 0.678 mmol) in about 15 mL EtOH total. To this slurry was added NaBH4 (0.128 g, 3.39 mmol). The mixture bubbled and became warm, and was cooled briefly with an ice bath, then allowed to stir at ambient temperature overnight. 10 mL THF was added, followed by additional NaBH4 (0.128 g, 3.39 mmol). After 5 h, the reaction mixture was concentrated in vacuo, partitioned between DCM and 1N aq. HCl, and extracted with DCM. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The material was treated with 10% MeOH in DCM and adsorbed onto 2 g silica gel, dried, and passed through a Redi-Sep® pre-packed silica gel column (40 g) using 0-10% MeOH/DCM. The product-containing fractions were concentrated to give N-(4-(3-fluoro-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide as a white solid. MS (ESI) m/z: calculated: 505.2; Observed: 506.0 (M++1).

Provenance & Evidence