反应详情

A solution of N-Boc-4-amino-2-fluorophenol (228 mg, 1.0 mmol) in DMF (2 mL) was treated with t-BuOK (124 mg, 1.1 mmol) and the mixture stirred at room temperature for 2 h. The mixture was treated with 4-chloropyridine-2,6-dicarboxamide (200 mg, 1.0 mmol) and K2CO3 (35 mg, 0.5 mmol) and heated at 80° C. for 1.5 h. The mixture was concentrated in vacuo, treated with EtOAc (10 mL) and H2O (10 mL) and filtered to remove the insoluble material. The EtOAc phase was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the residue by flash column chromatography on SiO2 eluting with 30-100% EtOAc/hexanes gave the title compound (170 mg, 44%) as a white solid containing 10% of the starting chloropyridine. 1H NMR (DMSO-d6) δ 9.77 (s, 1H), 8.86 (s, 2H), 7.87 (s, 1H), 7.63 (d, 1H, J=12.1 Hz), 7.55 (s, 2H), 7.38-7.31 (m, 2H), 1.48 (s, 9H).

1. temperatureheated at 80° C. for 1.5 h
2. concentrationThe mixture was concentrated in vacuo
3. additiontreated with EtOAc (10 mL) and H2O (10 mL)
4. filtrationfiltered
5. customto remove the insoluble material
6. washThe EtOAc phase was washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated in vacuo
9. customPurification of the residue by flash column chromatography on SiO2 eluting with 30-100% EtOAc/hexanes