反应详情

To a solution of 5-chloro-2-methoxy-3-[methyl(oxan-4-yl)amino]benzoic acid (200 mg, 0.67 mmol) in DMF (2 ml) at room temperature under nitrogen was added HBTU (304 mg, 0.80 mmol) followed by N-ethyl-N-(propan-2-yl)propan-2-amine (174 μl, 1.0 mmol) and 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 125 mg, 0.73 mmol). After stirring for 2 hours at room temperature 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 (10 g silica, Isolute cartridge, gradient of eluents; 100% DCM to 96:4 DCM:MeOH) to give 182 mg (63%) of the title compound as an off-white solid. LC-MS 98%, m/z=434.1/436.1, 1H NMR (500 MHz, Chloroform-d) δ ppm 12.52 (br s, 1H), 8.76 (t, J=5.8 Hz, 1H), 7.69 (d, J=2.6 Hz, 1H), 7.01 (d, J=2.6 Hz, 1H), 5.94 (s, 1H), 4.56 (d, J=6.0 Hz, 2H), 3.99 (dd, J=11.2, 3.9 Hz, 2H), 3.72 (s, 3H), 3.49 (tt, J=11.5, 3.7 Hz, 1H), 3.36 (t, J=11.2 Hz, 2H), 2.67 (s, 3H), 2.42 (s, 3H), 2.31 (s, 3H), 1.93-1.73 (m, 2H), 1.64-1.52 (m, 2H).

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 (10 g silica, Isolute cartridge, gradient of eluents; 100% DCM to 96:4 DCM:MeOH)