反应详情

3-Amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate A) (397 mg, 1.392 mmol), 3-amino-1,1,1-trifluoro-2-methyl-propan-2-ol hydrochloride (250 mg, 1.392 mmol) and HATU (529 mg, 1.392 mmol) were dissolved in DMF (10 ml) and stirred at RT for 2 min. 4-Methylmorpholine (0.413 ml, 4.18 mmol) was added and stirring continued at RT for 3 h. The reaction mixture was poured onto ice/water (100 ml) and extracted with EtOAc (250 ml). The organic extract was washed with sat NH4Cl solution (˜50 ml), dried over MgSO4 and concentrated in vacuo to give a pale brown oil. The oil was dissolved in CHCl3 (˜3 ml) and loaded onto a 24 g ISCO (silica) column eluting with iso-hexane:EtOAc to afford the title product; LC-MS Rt=1.46 mins; [M+H]+ 410.1, Method 2minLC_v002. 1H NMR (400 MHz, DMSO-d6) δ 8.30 (NH, t), 7.72 (1H, s), 7.29 (NH2, b s), 6.28 (OH, s), 3.68 (1H, dd), 3.47 (1H, dd), 1.24 (3H, s). 19F NMR (400 MHz, DMSO-d6) δ −62.71 (CF3, s), −80.48 (CF3, s).

1. stirringstirring
2. waitcontinued at RT for 3 h
3. additionThe reaction mixture was poured onto ice/water (100 ml)
4. extractionextracted with EtOAc (250 ml)
5. extractionThe organic extract
6. washwas washed with sat NH4Cl solution (˜50 ml)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customto give a pale brown oil
10. washeluting with iso-hexane