Dichloromethane → HCID 72943527, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(4-Bromo-pyrazol-1-yl)-3,3-difluoro-piperidine (intermediate 29; 150 mg; 0.50 mmol; 1.0 eq.) in Dioxane-1,4 (12 mL) and Water (3.0 mL) was added Potassium carbonate (141 mg; 0.99 mmol; 2.0 eq.) and 2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrimidine (intermediate 30; 221 mg; 0.60 mmol; 1.2 eq.). The reaction mixture was degasified for 15 min and then 1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (20.88 mg; 0.02 mmol; 0.05 eq.) was added. The reaction mixture was then heated at 100° C. for 90 min. It was concentrated under reduced pressure, diluted with Water (15 mL) and extracted with ethylacetate (2×25 mL). Combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM: MeOH, 9:1) afforded the title compound as a brown solid (24 mg; 11%). 1H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 2H), 8.53-8.52 (m, 2H), 8.26 (s, 1H), 8.23-8.20 (m, 2H), 7.91 (s, 1H), 7.71 (d, J=8.1 Hz, 1H), 7.51 (t, J=7.8 Hz, 1H), 4.96-4.86 (m, 1H), 3.89 (s, 3H), 3.22-3.15 (m, 1H), 3.08-3.05 (m, 1H), 2.98-2.87 (m, 1H), 2.72-2.67 (m, 1H), 2.66-2.59 (m, 1H), 2.36-2.29 (m, 1H), 2.08-2.05 (m, 1H). HPLC (Condition A): Rt 3.00 min (purity 96.8%). MS (ESI+): 422.2.

Provenance & Evidence