反应详情

To a solution of 5-chloro-2-ethyl-3-[ethyl(oxan-4-yl)amino]benzoic acid (100 mg, 0.32 mmol) in DMF (2 ml) at room temperature under nitrogen was added HBTU (146 mg, 0.38 mmol) followed by N-ethyl-N-(propan-2-yl)propan-2-amine (84 μl, 0.48 mmol) and 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 60.3 mg, 0.35 mmol). After stirring for 3 hours at room EtOAc (30 ml) was added to the reaction mixture and this was then washed with deionized water (5 ml) followed by saturated NaHCO3(aq) (3×5 ml). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by FCC (5 g silica, Isolute cartridge, gradient of eluents; 100% EtOAc to 97:3 EtOAc:MeOH) to give 90 mg (63%) of the title compound as a white solid. LC-MS 97%, m/z=446.1/448.2, 1H NMR (500 MHz, Chloroform-d) δ ppm 11.93 (s, 1H), 7.14 (t, J=5.7 Hz, 1H), 7.10 (d, J=2.0 Hz, 1H), 7.04 (d, J=2.0 Hz, 1H), 5.95 (s, 1H), 4.52 (d, J=5.8 Hz, 2H), 3.95 (d, J=11.2 Hz, 2H), 3.30 (td, J=11.3, 3.6 Hz, 2H), 3.01 (q, J=7.0 Hz, 2H), 2.93 (ddd, J=15.3, 10.0, 5.3 Hz, 1H), 2.83 (q, J=7.4 Hz, 2H), 2.38 (s, 3H), 2.22 (s, 3H), 1.71-1.63 (m, 4H), 1.02 (t, J=7.5 Hz, 3H), 0.86 (t, J=7.0 Hz, 3H).

1. additionwas added to the reaction mixture
2. washthis was then washed with deionized water (5 ml)
3. dry with materialThe organic phase was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by FCC (5 g silica, Isolute cartridge, gradient of eluents; 100% EtOAc to 97:3 EtOAc:MeOH)