Ethanol → 4-(4-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl)-1-(2,4-difluorophenyl)-1H-pyrazolo[3,4-b]pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of Intermediate 63A (35.7 mg, 0.1 mmol) and Intermediate 102A (44.6 mg, 0.150 mmol) in a mixture of DME (1 mL), ethanol (0.5 mL) and water (0.5 mL) was added Na2CO3 (0.042 g, 0.400 mmol). This suspension was degassed with a stream of N2 for 10 minutes and then tetrakis(triphenylphosphine)palladium(0) (5.78 mg, 5.00 mmol) was added followed by degassing for 10 minutes. The tube was then sealed, heated at 90° C. for 14 hours, and cooled to room temperature. The contents of the tube were diluted with MeOH, filtered, rinsed with MeOH, and concentrated to a brown sludge. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of Example 103 was 6.0 mg, and its purity was approximately 100%. LC/MS (condition C): ret time=1.52 min, MS (ES): m/z=401.01 [M+H]+.

Provenance & Evidence