反应详情

To a suspension of 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-8-piperidin-4-yl-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene trifluoroacetic acid salt (350 mg, 0.71 mmol) in THF was added potassium carbonate (245 mg, 1.78 mmol) followed by N-isopropyl-2-chloroacetamide (106 mg, 0.78 mmol) and the reaction mixture stirred for 18 h at RT then heated at 50° C. for 2 h. The resultant mixture was concentrated in vacuo and the residue subjected to flash chromatography (SiO2, gradient 0 to 5% MeOH in DCM to give 247 as a white solid (180 mg, 53%). 1H NMR δ (ppm) (DMSO-d6): 8.28 (1H, d, J=8.28 Hz), 7.86 (1H, d, J=0.63 Hz), 7.85 (1H, s), 7.40 (1H, d, J=8.18 Hz), 7.03 (1H, dd, J=8.36, 1.77 Hz), 6.89 (1H, d, J=1.72 Hz), 5.88-5.79 (1H, m), 4.48-4.41 (4H, m), 3.89-3.83 (1H, m), 2.89-2.79 (4H, m), 2.13 (2H, td, J=10.70, 4.11 Hz), 1.74-1.64 (4H, m), 1.43 (6H, d, J=6.60 Hz), 1.04 (6H, d, J=6.59 Hz). 1 Proton obscured by solvent peak. LCMS: RT=2.94 min, M+H+=478

1. temperaturethen heated at 50° C. for 2 h
2. concentrationThe resultant mixture was concentrated in vacuo