反应详情

A stirred solution of 3-{[(2-amino-4-tert-butylphenyl)carbamoyl]methyl}-N-methoxy-N-methylcyclobutane-1-carboxamide (70%, 2.62 g, 5.28 mmol) in acetic acid (25 ml) was heated to reflux for 1 h. The reaction mixture was concentrated under reduced pressure, and the residue partitioned between sat. NaHCO3 (aq) (25 ml) and EtOAc (25 ml), and the layers separated. The aqueous layer was extracted with EtOAc (2×25 ml), the combined organics were washed with brine (50 ml), dried (MgSO4) and concentrated. The crude material was purified by silica flash column chromatography, eluting with 1-10% 2M NH3 in MeOH in DCM to afford the title compound (2.02 g, 93%) as a yellow gum: MS (ESI+) for C19H27N3O2 m/z 330.5 [M+H]+; LC purity 80% (UV), 100% (ELS), (ret. time, 1.51 min); 1H NMR (500 MHz, CHLOROFORM-d) δH ppm 7.56 (br. s., 1 H), 7.48 (d, J=8.5 Hz, 1 H), 7.30 (dd, J=8.5 Hz, 1 H), 3.80-3.90 (m, 1 H), 3.65 (s, 3 H), 3.47-3.57 (m, 1 H), 3.20 (s, 3 H), 2.94-3.13 (m, 2 H), 2.88 (dt, J=16.1, 8.1 Hz, 1 H), 2.32-2.60 (m, 2 H), 2.01-2.17 (m, 2 H), 1.38 (s, 9 H).

1. temperatureto reflux for 1 h
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customthe residue partitioned between sat. NaHCO3 (aq) (25 ml) and EtOAc (25 ml)
4. customthe layers separated
5. extractionThe aqueous layer was extracted with EtOAc (2×25 ml)
6. washthe combined organics were washed with brine (50 ml)
7. dry with materialdried (MgSO4)
8. concentrationconcentrated
9. customThe crude material was purified by silica flash column chromatography
10. washeluting with 1-10% 2M NH3 in MeOH in DCM