Potassium Carbonate → HCID 178480055, compound

Participants

Reaction Conditions

Reaction Steps

5-Bromo-2-[3-(1-methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidine (intermediate 2; 700 mg; 2.22 mmol; 1.0 eq.), 4,4,5,5,4′,4′,5′,5′-Octamethyl-[2,2′]bi[[1,3,2]dioxaborolanyl](620 mg; 2.44 mmol; 1.1 eq.), Potassium acetate (327 mg; 3.33 mmol; 1.5 eq.) and trans-Dichlorobis(tricyclohexylphosphine)palladium(II), 99% (16.4 mg; 0.02 mmol; 0.01 eq.) were flushed with nitrogen for 10 min before the addition of Dioxane-1,4 (15 mL). The reaction mixture was then heated at reflux under nitrogen for 4 h. The temperature was reduced to 70° C. before the addition of trans-4-(4-Iodo-pyrazol-1-yl)-cyclohexanol (intermediate 22; 714 mg; 2.44 mmol; 1.10 eq.), potassium carbonate (921 mg; 6.66 mmol; 3.0 eq.), trans-Dichlorobis(tricyclohexylphosphine)palladium(II), 99% (16.4 mg; 0.02 mmol; 0.01 eq.) and water (5 mL). The new reaction mixture was heated again at 100° C. for 30 min. It was allowed to cool to RT and diluted with EtOAc. Organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by flash chromatography on silica (THF: EtOAc, 50:50) followed by a recrystallisation in THF afforded the tittle compound as an off-white powder (550 mg, 62%). 1H NMR (300 MHz, DMSO) δ 9.14 (s, 2H), 6.51 (m, 1H), 8.48 (s, 1H), 8.25 (s, 1H), 8.20 (m, 1H), 8.11 (s, 1H), 7.91 (s, 1H), 7.69 (m, 1H), 7.50 (t, J=8.1 Hz, 1H), 4.70 (d, J=4.2 Hz, 1H), 4.18 (m, 1H), 3.88 (s, 3H), 3.50 (m, 1H), 1.73-2.08 (m, 6H), 1.36 (m, 2H). HPLC (Condition A): Rt 3.21 min (purity 98.6%). MS (ESI+): 459.4.

Provenance & Evidence