反应详情

EDC (229.4 mg, 1.2 mmol) was added to a solution of methyl (±)-7-carboxy-4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2-acetate (292.3 mg, 1.0 mmol), 3-(aminomethyl)pyridine (0.122 mL, 1.2 mmol), HOBT.H2O (162.2 mg, 1.2 mmol), and diisopropylethylamine (0.35 mL, 2.0 mmol) in anhydrous DMF (5 mL) at RT. After 23.5 h, the reaction was concentrated on the rotavap (high vacuum), and the residue was partitioned between 10% aqueous Na2CO3 and CHCl3. This caused a solid to precipitate. The layers were separated and the aqueous layer was extracted exhaustively with CHCl3 until all solids had dissolved. The combined CHCl3 layers were diluted with CHCl3, washed with 10% Na2CO3, dried (MgSO4), and concentrated. Crystallization of the residue from EtOAc gave impure title compound. The mother liquors were concentrated, combined with the recrystallized residue and chromatographed (silica gel, 10% MeOH/CHCl3). The title compound was obtained as a colorless solid (341 mg, 89%): TLC Rf 0.37 (10% MeOH/CHCl3); 1H NMR (250 MHz, CDCl3) δ8.58-8.68 (m, 1H), 8.47-8.57 (m, 1H), 7.72-7.81 (m, 1H), 7.54 (d, J=2.1 Hz, 1H), 7.45 (dd, J=8.5, 2.1 Hz, 1H), 7.31 (dd, J=7.7, 4.8 Hz, 1H), 6.44-6.63 (m, 2H), 5.45 (d, J=16.4 Hz, 1H), 5.04-5.15 (m, 1H), 4.64 (d, J=5.9 Hz, 2H), 4.55 (br d, J=4.5 Hz, 1H), 3.76 (d, J=16.4 Hz, 1H), 3.75 (s, 3H), 3.07 (s, 3H), 2.99 (dd, J3=16.0, 6.7 Hz, 1H), 2.67 (dd, J=16.0, 6.4 Hz, 1H); MS (ES) m/e 383.2 (M+H)+.

1. customat RT
2. concentrationthe reaction was concentrated on the rotavap (high vacuum)
3. customthe residue was partitioned between 10% aqueous Na2CO3 and CHCl3
4. customto precipitate
5. customThe layers were separated
6. extractionthe aqueous layer was extracted exhaustively with CHCl3 until all solids
7. dissolutionhad dissolved
8. additionThe combined CHCl3 layers were diluted with CHCl3
9. washwashed with 10% Na2CO3
10. dry with materialdried (MgSO4)
11. concentrationconcentrated
12. customCrystallization of the residue from EtOAc