反应详情

(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (0.083 g, 0.25 mmol), 4-chloro-2-methylnicotinonitrile (0.035 g, 0.23 mmol) and diisopropylethylamine (0.160 mL, 0.92 mmol) in isopropanol (1 mL) was heated to 80° C. in a sealed tube under argon for 2 h then at 75° C. for 86 h. The reaction mixture was cooled, diluted with EtOAc (20 mL) and washed with water (10 mL). The organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-8% (9:1 MeOH/0.880 NH3) in DCM). Product containing fractions were evaporated and freeze dried to give 340 as a pale brown solid, (21 mg, 24%). LCMS (Method C): RT 3.11 min [M+H]+ 372.08. 1H NMR δ (ppm DMSO-d6): 7.98 (1H, d, J=6.15 Hz), 7.77 (1H, dd, J=8.82, 4.86 Hz), 7.52-7.50 (5H, m), 7.12-7.11 (2H, m), 6.85 (1H, dd, J=8.91, 2.51 Hz), 6.40 (1H, d, J=6.24 Hz), 5.11 (1H, dq, J=7.04 Hz), 2.41 (3H, s), 1.56 (3H, d, J=6.64 Hz)

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