1-Hydroxybenzotriazole → 2-(4-Fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(5-methyloxazol-4-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide

Participants

Reaction Steps

To a mixture of 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (0.2 g, 0.46 mmol, 1 eq), 1-(5-methyloxazol-4-yl)cyclopropanamine (0.06 g, 0.46 mmol, 1.0 eq), HOBT (0.062 g, 0.46 mmol, 1.0 eq), EDC.HCl (0.08, 0.46 mmol, 1.0 eq), in DCM at ambient temperature and under a nitrogen atmosphere was added diisopropylehtylamine (0.19 ml, 1.3 mmol, 3.0 eq). The clear mixture was stirred at ambient temperature for 12 h. The mixture was concentrated, diluted with water and extracted with EtOAc. The organic layer was further washed with water, dried over sodium sulphate and concentrated. The product obtained was purified by Combiflash column chromatography (4 g flash column, CV 4.8 ml, 18 ml/min, max pressure 200 psi) using 0.5% Methanol/DCM. Yield: 0.045 g (17.6%) 1H NMR (400 MHz, DMSO-d6): δ 1.11-1.14 (m, 2H), 1.20-1.23 (m, 2H), 2.29 (s, 3H), 2.31 (s, 3H), 2.82 (d, 3H, J=4.4 Hz), 3.95 (s, 3H), 7.12 (s, 1H), 7.33 (dd, 1H, J=1.6, 8.4 Hz), 7.40 (apparent t, 2H, J=8.8 Hz), 7.49 (d, 1H, J=1.2 Hz), 7.60 (s, 1H), 7.72 (d, 1H, J=8.4 Hz), 7.97-8.01 (m, 2H), 8.04 (s, 1H), 8.46-8.48 (m, 1H), 8.67 (s, 1H).

Provenance & Evidence