反应详情

To a solution of aniline 380 (0.31 g, 0.71 mmol) and DIPEA (0.7 ml, 0.4 g, 3 mmol) in dry DMF (5 mL) was added acid 27 (0.30 g, 1.4 mmol), HOBt (0.040 g, 0.30 mmol), and EDC×HCl (0.40 g, 2.1 mmol) and the mixture was stirred at r.t. for 18 h. Additional EDC×HCl (0.050 g, 0.26 mmol) was added, and the mixture was stirred for a further 6 h. It was then partitioned between ethyl acetate and water. The organic phase was collected, washed with water, dried (anhydrous MgSO4), filtered, and concentrated. Flash chromatography (chloroform/NH4OH) of the residue followed by re-crystallization (90% ethyl acetate/methanol) provided 378 (0.15 g, 32% yield) as a colorless solid. 1H NMR (400 MHz. DMSO-d6) δ (ppm): 10.58 (br s, 1H); 9.63 (br s, 1H); 8.68 (dd, J=2.7, 0.8, 1H); 8.48 (d, J=5.5, 1H); 8.20 (dd, J=8.6, 2.7, 1H); 8.05 (d, J=7.6, 1H); 8.03 (s, 1H); 7.86 (dd, J=13.1, 2.3, 1H); 7.49 (t, J=8.8, 1H); 7.42 (dd, J=8.8, 1.4, 1H); 7.09-7.03 (m, 2H); 6.94 (dd, J=8.8, 0.7, 1H); 6.92-6.88 (m, 1H); 6.61 (dd, J=5.5, 1.0, 1H); 4.33 (t, J=6.7, 2H); 3.85 (s, 3H); 3.63 (s, 2H); 2.33 (t, J=7.2, 2H); 2.13 (s, 6H); 1.84 (quint, J=7.2, 2H). LRMS (M+H): 630.2.

1. stirringthe mixture was stirred for a further 6 h
2. customIt was then partitioned between ethyl acetate and water
3. customThe organic phase was collected
4. washwashed with water
5. dry with materialdried (anhydrous MgSO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customFlash chromatography (chloroform/NH4OH) of the residue followed by re-crystallization (90% ethyl acetate/methanol)