Ethyl Acetate → HCID 178485296, compound

Participants

Reaction Steps

Intermediate 63 (50 mg, 0.12 mmol) in dimethylformamide was reacted with 2-(bromomethyl)-4′-cyano-N-methyl-1,1′-biphenyl-4-carboxamide (63a) (40 mg, 0.12 mmol), cesium carbonate (20 mg, 0.06 mmol) and the resulting suspension stirred under a nitrogen atmosphere at rt for 3h at which point ethyl acetate (30 mL) was added. The organic phase was washed with water (2×25 mL) and brine (1×), dried (Na2SO4), and concentrated on a rotary evaporator. The resulting residue was dissolved in 10% methanolic sodium hydroxide (5 mL) and water (2 mL) was added. The resulting solution was stirred at rt under a nitrogen atmosphere for 30 minutes at which point 10% hydrochloric acid was added until pH=2. This solution was extracted with ethyl acetate, dried (Na2SO4), and concentrated on a rotary evaporator and the residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid) to afford the product as a white solid (6 mg, 7%). 1H NMR (CD3OD) δ 9.16 (s, 1H), 8.7 (br s, 1H), 8.15 (d, 1H, J=1.46), 7.94 (dd, 1H, J=8.06, 1.83), 7.80 (d, 2H, J=8.42), 7.71 (br m, 2H), 7.65 (d, 2H, J=8.06), 7.49 (d, 1H, J=8.06), 7.17 (d, 2H, 6.59), 5.14 (s, 1H), 4.46 (br m, 1H), 2.96 (s, 3H), 2.83 (br m, 2H), 1.96 (br m, 4H), 1.75 (br m, 1H), 1.39 (br m, 3H); ESI-MS m/e 610.24 (M+H); HPLC purity (ELSD)>95%.

Provenance & Evidence