反应详情

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (0.106 g, 0.32 mmol), 4-chloroimidazo[2,1-f][1,2,4]triazine (WO2010/014930) (0.050 g, 0.32 mmol) and diisopropylethylamine (0.222 mL, 1.28 mmol) in isopropanol (2 mL) was heated to 60° C. in a sealed tube for 0.5 h. The reaction mixture was cooled and diluted with EtOAc (20 mL) and washed with water (2 mL) The organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM). Product containing fractions were evaporated and freeze dried to give 321 as a pale pink solid, (94 mg, 78%). LCMS (Method C): RT 4.31 min [M+H]+ 374.01. 1H NMR δ (ppm) (DMSO-d): 9.15 (1H, d, J=7.24 Hz), 8.02 (1H, d, J=1.09 Hz), 7.95 (1H, s), 7.71 (1H, dd, J=8.81, 4.85 Hz), 7.57-7.54 (3H, m), 7.48-7.39 (3H, m), 7.10 (1H, td, J=9.33, 2.51 Hz), 6.83 (1H, dd, J=8.91, 2.52 Hz), 5.57 (1H, dq, J=7.00 Hz), 1.61 (3H, d, J=6.88 Hz)

1. temperatureThe reaction mixture was cooled
2. washwashed with water (2 mL) The organic extracts
3. dry with materialwere dried (Na2SO4)
4. customevaporated to dryness
5. custompurified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM)
6. additionProduct containing fractions
7. customwere evaporated
8. customfreeze dried