Potassium Phosphate, Tribasic → (R)-4-((R)-1-(6-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

Intermediate 2.64 (25 mg, 0.076 mmol), 1-(2,2-difluoroethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (40 mg, 0.16 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (1.6 mg, 0.0023 mmol) and K3PO4 (52 mg, 0.25 mmol) were taken up in 1,4-dioxane (0.9 mL) under Ar. Water (0.1 mL) was added and the resulting stirred mixture was heated to 100° C. After 1.25 h, the reaction mixture was cooled to r.t. and was diluted with EtOAc (2 mL), water (1 mL), and brine (1 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (4×1.5 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated. The resulting crude residue was purified by silica gel chromatography (0% to 15% MeOH in DCM) to afford (R)-4-((R)-1-(6-(1-(2,2-difluoroethyl)-1H-pyrazol-4-yl)-3-(difluoromethyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.26. LCMS-ESI+ (m/z): [M+H]+ calcd for C15H19F4N6O2: 427.2; found 426.8. 1H NMR (400 MHz, Chloroform-d) δ 8.26 (s, 1H), 8.01 (s, 1H), 7.91 (s, 1H), 7.60 (t, J=61.1 Hz, 1H), 7.51 (s, 1H), 6.32-5.97 (m, 2H), 5.72-5.58 (m, 1H), 4.51 (td, J=13.5, 4.3 Hz, 2H), 3.65-3.52 (m, 1H), 3.36 (dd, J=9.7, 6.1 Hz, 1H), 3.00-2.84 (m, 1H), 2.55 (dd, J=17.2, 9.3 Hz, 1H), 2.44 (dd, J=17.2, 7.3 Hz, 1H), 1.48 (d, J=6.2 Hz, 3H).

Provenance & Evidence