反应详情

温度

125 °C

A solution of the 3-({[2-amino-5-(trifluoromethyl)phenyl]carbamoyl}methyl)-N-methoxy-N-methylcyclobutane-1-carboxamide (0.82 g, 2.29 mmol) in AcOH (10 ml) was heated to reflux (˜125° C.) whilst stirring for 2.5 h. The reaction was monitored by LC MS. The reaction mixture was allowed to cool to RT and then evaporated in vacuo. The residue was dissolved in DCM (30 ml) and washed with sat. NaHCO3 (50 ml), dried over Na2SO4, filtered and evaporated. The crude was purified by silica gel column chromatography, eluting with MeOH:DCM (2:98-5:95) to give a yellow-brown oil (0.75 g, 94%); MS (ESI+) for C16H18F3N3O2 m/z 342.10[M+H]+; HPLC purity 97% (ret. time, 1.40 min); 1H NMR (500 MHz, MeOD) δH ppm 1.96-2.17 (2 H, m), 2.27-2.55 (2 H, m), 2.66-2.92 (1 H, m), 2.97-3.15 (2 H, m), 3.15-3.22 (3 H, m), 3.32-3.62 (1 H, m), 3.63-3.73 (3 H, m), 7.37-7.53 (1 H, m), 7.53-8.00 (2 H, m).

1. temperatureto cool to RT
2. customevaporated in vacuo
3. dissolutionThe residue was dissolved in DCM (30 ml)
4. washwashed with sat. NaHCO3 (50 ml)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customThe crude was purified by silica gel column chromatography
9. washeluting with MeOH:DCM (2:98-5:95)