反应详情

To a solution of 3-(benzyloxy)-10-(((benzyloxy)carbonyl)amino)-4-oxo-4,6,7,8,9,10-hexahydro-7,10-ethanopyrimido[1,2-a]azepine-2-carboxylic acid, Intermediate 4 (400 mg, 0.817 mmol) in CH2Cl2 (8 mL) was added oxalyl chloride (0.114 mL, 1.307 mmol) followed by 1 drop of DMF. After stirring for 2 h, the mixture was concentrated under reduced pressure. The crude acid chloride was then diluted with dichloromethane (5 mL)) and added to a stirred solution of 1-amino-3-(4-fluorophenyl)propan-2-one HCl (183 mg, 0.899 mmol) and triethylamine (0.456 mL, 3.27 mmol) in CH2Cl2 (8.00 mL) and the resulting solution stirred at room temperature. After 16 h the reaction mixture was poured into sat. NaHCO3 and extracted with dichloromethane (50 mL×3), dried (Na2SO4), filtered and concentrated to give a yellow oil. The crude product was then purified by silica gel chromatography (50-100% EtOAc/hexane) to afford the title compound (400 mg, 0.626 mmol, 77% yield) as a light yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.99 (1H, br. s.), 7.49 (2H, d, J=5.80 Hz), 7.28-7.37 (8H, m), 7.15 (2H, dd, J=8.55, 5.49 Hz), 7.01-7.04 (2H, m), 6.79 (1H, br. s.), 5.32 (2H, s), 5.06 (2H, s), 4.17 (2H, d, J=4.88 Hz), 4.12 (2H, d, J=3.66 Hz), 3.69 (2H, s), 2.67-2.78 (2H, m), 2.47 (1H, br. s.), 1.89-2.01 (4H, m), 1.64-1.72 (2H, m). LCMS (M+H)=640.04.

1. concentrationthe mixture was concentrated under reduced pressure
2. additionThe crude acid chloride was then diluted with dichloromethane (5 mL)) and
3. stirringthe resulting solution stirred at room temperature
4. extractionextracted with dichloromethane (50 mL×3)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customto give a yellow oil
9. customThe crude product was then purified by silica gel chromatography (50-100% EtOAc/hexane)