反应详情

5-{(9aS)-3-(ethoxycarbonyl)-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizin-4-yl}-3-furoic acid (0.100 g, 0.209 mmol) was dissolved in CH2Cl2. 1-aminoindane (0.037 mL, 0.313 mmol) was added followed by EDCI (0. 048 g, 0.251 mmol) and HOBt (0.034 g, 0.251 mmol). After 14 h of stirring at ambient temperature the reaction mixture was poured onto 5% HCl solution and extracted with CH2Cl2. The organics were washed with sat'd NaHCO3, brine and then dried (Na2SO4), filtered and concentrated to a brown residue. Chromatography on silica gel using 4:1 EtOAc:Hexanes eluted the product to provide the title compound upon concentration as a white solid (0.062 g, 0.105 mmol, 50% yield): 1H NMR (CDCl3, 400 MHz) δ 8.12 (s, 1H), 8.11 (d, J=9.5 Hz, 1H), 7.32 (m, 1H), 7.25–7.15 (m, 5H), 6.96 (t, J=8.6 Hz, 2H), 6.32 (m, 1H), 5.69 (dd, J=15.5, 7.7 Hz, 1H), 4.65 (dd, J=10.4, 6.2 Hz, 1H), 4.37 (dd, J=14.2, 7.0), 3.73–3.63 (m, 1H), 3.44–3.38 (m, 1H), 3.17–3.01 (m, 5H), 2.92–2.83 (m, 1H), 2.68–2.60 (m, 1H), 2.48–2.40 (m,1H), 2.37–2.25 (m, 2H), 1.96–1.86 (m, 1H), 1.38–1.30 (m, 1H), 1.27 (t, J=7.1 Hz, 3H); ESMS m/z 594 (M+H)+, 592 (M−H)+; Anal. Calcd. For C35H32FN3O5.½H2O: C, 69.75; H, 5.52; N, 6.97; found: C, 69.58; H, 5.43; N, 7.05.

1. extractionextracted with CH2Cl2
2. washThe organics were washed with sat'd NaHCO3, brine
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated to a brown residue
6. washChromatography on silica gel using 4:1 EtOAc:Hexanes eluted the product