反应详情

A stirred mixture of 4-(7-(6-aminopyridin-3-yloxy)thieno[3,2-b]pyridin-2-yl)-N-methyl-benzamide (11 mg, 0.029 mmol) and 1-((4-fluorophenyl)carbamoyl)cyclopropanecarbonyl fluoride (9.9 mg, 0.044 mmol), in CH3CN (0.5 mL) was heated at 100° C. for 3 hours. After cooling to room temperature, the mixture was partitioned between EtOAc (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL). The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×5 mL). The combined organic phases were washed with brine (5 mL), dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC (0.5 mm thickness, Rf=0.30), eluting with 10% MeOH/CHCl3. The product was obtained as a beige solid (2 mg, 11%). HPLC: 100% purity (220 nm); LRMS (ESI+): 94% purity, 220 nm, m/z 582 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 9.59 (s, 1H), 9.01 (s, 1H), 8.53 (d, J=5 Hz, 1H), 8.29 (m, 2H), 7.85 (m, 5H), 7.55 (m, 3H), 7.04 (t, J=9 Hz, 2H), 6.56 (d, J=5 Hz, 1H), 6.19 (m, 1H), 3.06 (d, J=5 Hz, 3H), 1.82 (m, 2H), 1.68 (m, 2H).

1. customthe mixture was partitioned between EtOAc (5 mL) and 1:1 saturated aqueous NaHCO3/water (5 mL)
2. customThe phases were separated
3. extractionthe aqueous phase was re-extracted with EtOAc (2×5 mL)
4. washThe combined organic phases were washed with brine (5 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude was purified by preparative TLC (0.5 mm thickness, Rf=0.30)
9. washeluting with 10% MeOH/CHCl3