ACETAMIDRAZONE HCL

To an ice cooled, stirred mixture of 1 (50 mg, 0.13 mmol) in 1, 2-dichloroethane (0.42 mL) was added oxalyl chloride (0.11 mL, 1.26 mmol) and the resulting thick slurry was stirred at room temperature for 2 h. The mixture was concentrated in vacuo, azeotroped with toluene and the resulting solids dissolved in tetrahydrofuran (3 mL). Acetamidrazone hydrochloride (41 mg, 0.38 mmol) and triethylamine (39 mg, 0.38 mmol) were added and the mixture was stirred for 3 h. The reaction was concentrated in vacuo and purified via medium pressure silica gel chromatography (10 g column, 15 mL/min, 5-10% methanol/dichloromethane) to afford 70 as a white solid, 18 mg. A stirred solution of 70 (18 mg, 0.04 mmol) in DMF (1 mL) was heated at 140 C for 4 h, concentrated in vacuo and purified via medium pressure silica gel chromatography (10 g column, 15 mL/min, 5-10% methanol/dichloromethane) to afford the title compound as a yellow solid, 0.5 mg. 1H NMR (400 MHz, chloroform-d) delta 8.25 (s, 1H), 7.23-7.28 (m, 2H), 7.12-7.18 (m, 2H), 4.65 (dd, J = 4.98, 3.61 Hz, 2H), 3.90-4.02 (m, 2H), 2.34-2.42 (m, 6H), 2.12 (d, J = 6.83 Hz, 1H), 1.90 (br s, 5H), 1.40-1.60 (m, 3H). LCMS (ESI) m/z: 432 (M+H).