1,2-Dichloroethane → Tert-butyl 4-(1-(3,4-dichlorophenyl)-3-(methylcarbamoyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate

Participants

Reaction Steps

To a mixture of 4-(1-(tert-butoxycarbonyl)piperidin-4-yloxy)-1-(3,4-dichlorophenyl)-6-oxo-1,6-dihydropyridazine-3-carboxylic acid (23 mg, 0.047 mmol) in THF (1 ml) at room temperature under argon was added HOBt (8.0 mg, 0.052 mmol), EDC (10.01 mg, 0.052 mmol), and was followed by 1 M methylamine in THF (0.237 mL, 0.237 mmol). The reaction mixture was stirred at room temperature overnight. EtOAc (10 mL) and 1 N NaOH (10 mL) were added to the reaction mixture. Layers were separated. Organic layer were washed with water (10 mL), and brine (10 mL). Organic phase was dried (MgSO4), filtered and concentrated. The crude product was purified by preparative HPLC (C18 column; 10-100% methanol in water without TFA) to give tert-butyl 4-(1-(3,4-dichlorophenyl)-3-(methylcarbamoyl)-6-oxo-1,6-dihydropyridazin-4-yloxy)piperidine-1-carboxylate (10 mg, white solid, 40.9%). 1H NMR (400 MHz, CDCl3) δ ppm 1.45 (s, 9H) 1.78-2.05 (m, 4H) 2.96 (d, J=5.27 Hz, 3H) 3.43-3.57 (m, 2H) 3.57-3.72 (m, 2H) 4.49-4.71 (m, 1H) 6.28 (s, 1H) 6.58-6.69 (m, J=3.95 Hz, 1H) 7.46 (dd, 1H) 7.54 (d, 1H) 7.70 (d, J=2.20 Hz, 1H). MS (ESI) 441 (M+H-tBu).

Provenance & Evidence