反应详情

温度

170 °C

A mixture of 5-chloropyridazin-4-amine (50 mg, 0.3860 mmol), 4-[(3,3-difluoropyrrolidin-1-yl)methyl]piperidine (197.1 mg, 0.9650 mmol) in NMP (10 mL) were heated under microwave conditions at 170° C. for 7 hours. The reaction was passed through a 10 g SCX-2 cartridge and washed with MeOH/DCM mixtures. The product was eluted by washing the cartridge with 2M NH3 in MeOH/DCM mixtures. The solvent was removed in vacuo and the residue was purified by column chromatography (ISCO Companion, 12 g column, eluting with 0 to 10% MeOH/DCM, loaded in DCM) to give the sub-title product as a beige solid (27 mg, 23% Yield). 1H NMR (500 MHz, DMSO) δ 8.46 (d, 1H), 8.41 (s, 1H), 5.85 (s, 2H), 3.20 (d, 2H), 2.87 (t, 2H), 2.69 (t, 2H), 2.59 (td, 2H), 2.34 (d, 2H), 2.24 (tt, 2H), 1.83-1.74 (m, 2H), 1.65-1.53 (m, 1H), 1.43-1.30 (m, 2H); 19F NMR (471 MHz, DMSO) δ −90.81; LC-MS ES+: 298.1, ES−: 296.1.

1. washwashed with MeOH/DCM mixtures
2. washThe product was eluted
3. washby washing the cartridge with 2M NH3 in MeOH/DCM mixtures
4. customThe solvent was removed in vacuo
5. customthe residue was purified by column chromatography (ISCO Companion, 12 g column, eluting with 0 to 10% MeOH/DCM, loaded in DCM)