反应详情

A solution of 2-(4-fluorophenyl)acetyl isocyanate (Compound D of Example 11, 0.29 M in toluene, 54.9 mL, 15.9 mmol, 2.1 eq) was added to 4-(4-amino-2-fluorophenoxy)picolinamide (1.86 g, 7.53 mmol, 1.0 eq) in 10/3 DCM/DMF (65 mL) at room temperature and the reaction mixture was stirred for 17 h. The reaction mixture was concentrated in vacuo and the residue redissolved in CHCl3. The organic layer was washed with saturated aqueous NaCl, the organic fraction separated, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (eluting ⅓ hexane/EtOAc, then to elute product 5% MeOH in CHCl3), and the appropriate fractions concentrated in vacuo to afford the product (2.2 g, 69%) as a solid. 1H NMR (DMSO-d6) δ 11.07 (s, 1H), 10.62 (s, 1H), 8.54 (d, 1H, J=5.60 Hz), 8.16-8.19 (m, 1H), 7.76-7.84 (m, 2H), 7.35-7.49 (m, 5H), 7.16-7.23 (m, 3H), 3.76 (s, 2H); MS(ESI+) m/z 427 (M+H)+. HRMS (ESI+) calcd.: 427.1218, found: 427.1214.

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionthe residue redissolved in CHCl3
3. washThe organic layer was washed with saturated aqueous NaCl
4. customthe organic fraction separated
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel chromatography (
9. washeluting ⅓ hexane/EtOAc
10. washto elute product 5% MeOH in CHCl3), and the appropriate fractions
11. concentrationconcentrated in vacuo