Water → HCID 178434530, compound

Participants

Reaction Conditions

Reaction Steps

cis-(5-Bromo-thiophen-3-yl)-(octahydro-quinolin-1-yl)-methanone (0.09 g, 0.27 mmol) was combined with 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (62 mg, 0.3 mmol), caesium carbonate (0.134 g, 0.41 mmol), and palladium tetrakis(triphenylphosphine) (0.031 g, 0.03 mmol) in DME (3 mL), IMS 0.6 mL) and water (0.3 mL). The reaction mixture was degassed then heated by microwave irradiation to 140° C. for 20 minutes then further quantities of 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.062 g), caesium carbonate (0.067 g), and palladium tetrakis(triphenylphosphine) (0.031 g) were added. The mixture was heated by microwave irradiation to 140° C. for 20 minutes followed by addition of 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.062 g) and further heating at 140° C. for 20 minutes. Further quantities of 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.062 g), caesium carbonate (0.097 g), and palladium tetrakis(triphenylphosphine) (0.031 g) were added and the mixture heated by microwave irradiation to 140° C. for a final 20 minutes before diluting with water and extraction with DCM (×3). The organic solution was dried over sodium sulfate, filtered and the solvent removed by evaporation. The residue was purified by chromatography on a silica II cartridge, eluting with 10-50% ethyl acetate in cyclohexane and then was further purified by HPLC, eluting with 5%-98% acetonitrile in water (0.1% formic acid) over 20 minutes. The fractions containing the desired product were freeze-dried to give the title compound as a white solid (0.027 g). LCMS m/z 330.30 [M+H]+ R.T.=9.62 min (Analytical Method 2).

Provenance & Evidence