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}-2-thiophenecarboxylic acid (0.100 g, 0.202 mmol) was dissolved in CH2Cl2 (2 mL). R-(−)-1-aminoindane (0.026 mL, 0.303 mmol) was added followed by EDCI (0.047 g, 0.243 mmol) and HOBt (0.033 g, 0.243 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 (0.066 g, 0.108 mmol, 54% yield): 1H NMR (CDCl3, 400 MHz) δ 7.48 (d, J=3.7 Hz, 1H), 7.36 (d, J=6.7 Hz, 1H), 7.28–7.20 (m, 2H), 7.19–15 (m, 3H), 6.97 (t, J=8.6 Hz, 2H), 6.24–6.20 (m, 1H), 5.67 (dd, J=15.3, 7.6 Hz, 1H), 4.69 (dd, J=10.3, 6.4 Hz, 1H), 4.19 (dd, J=14.3, 7.1), 3.76–3.66 (m, 1H), 3.42–3.36 (m, 1H), 3.18–3.01 (m, 5H), 2.96–2.87 (m, 1H), 2.71–2.66 (m, 1H), 2.48–2.40 (m, 1H), 2.37–2.25 (m, 2H), 1.96–1.86 (m, 1H), 1.42–1.35 (m, 1H), 1.13 (t, J=7.1 Hz, 3H); ESMS m/z 610 (M+H)+, 608 (M−H)+; Anal. Calcd. For C35H32F1N3O4S.½H2O: C 67.94 H, 5.38; N, 6.79; found C, 68.09 H 5.31 N 6.80.

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