Phosphorus oxychloride → 5-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-N-phenyl-1,3,4-oxadiazol-2-amine

Participants

Reaction Steps

A brown solution of 2-(3-(6-cyclopropylpyrazin-2-yl)-1H-indole-5-carbonyl)-N-phenylhydrazinecarboxamide (118.5 mg, 0.287 mmol) and phosphorus oxychloride (3.5 mL, 37.56 mmol) was stirred at 100° C. for 13 h. The reaction was cooled to RT, and excess POCl3 was removed in vacuo. The residue was partitioned between EtOAc (80 mL) and saturated aq NaHCO3 (50 mL). The organic layer was separated, washed with brine (30 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 10-100% EtOAc/Hex) furnished 5-(3-(6-cyclopropylpyrazin-2-yl)-1H-indol-5-yl)-N-phenyl-1,3,4-oxadiazol-2-amine (36.0 mg, 0.091 mmol, 32%) as a tan solid: MS (ESI, pos. ion) m/z: 395.1 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.01 (1H, br. s.), 10.53 (1H, s), 9.02 (1H, s), 8.91 (1H, s), 8.37 (1H, d, J=2.7 Hz), 8.36 (1H, s), 7.69-7.74 (1H, m), 7.63 (3H, dd, J=8.5, 1.7 Hz), 7.37 (2H, t, J=7.9 Hz), 7.02 (1H, t, J=7.3 Hz), 2.20-2.30 (1H, m), 1.16-1.21 (2H, m), 1.09-1.15 (2H, m).

Provenance & Evidence