反应详情

To a mixture of 4-chloronicotinic acid (Lancaster Synthesis, 0.31 g, 2.0 mmol) and 2,4-difluoroaniline (Aldrich, 0.20 mL, 2.0 mmol) in anhydrous dichloromethane (5 mL) was added bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBroP®, Novabiochem, 1.4 g, 3.0 mmol) followed by diisopropylethylamine (1.1 mL, 6.4 mmol). Anhydrous DMF (2 mL) was added to the mixture and the reaction stirred at ambient temperature. After 255 hours, the reaction mixture was partitioned between chloroform and 10% LiCl (aq). The organic layer was washed three times with 10% LiCl (aq), dried over anhydrous MgSO4, then concentrated in vacuo. Purification of the residue by flash column chromatography (SiO2, eluting with 1:1 hexane/EtOAc) afforded the desired compound (0.23 g, 42%). 1H NMR (DMSO-d6) δ 10.58 (s, 1H), 8.78 (s, 1H), 8.66 (d, 1H, J=5.4 Hz), 7.82-7.88 (m, 1H), 7.71 (d, 1H, J=5.4 Hz), 7.37-7.43 (m, 1H), 7.14-7.19 (m, 1H);

1. customthe reaction mixture was partitioned between chloroform and 10% LiCl (aq)
2. washThe organic layer was washed three times with 10% LiCl (aq)
3. dry with materialdried over anhydrous MgSO4
4. concentrationconcentrated in vacuo
5. customPurification of the residue
6. washby flash column chromatography (SiO2, eluting with 1:1 hexane/EtOAc)