反应详情

4-((9aS)-3-(Ethoxycarbonyl)-5-oxo-2-{2-[4-(trifluoromethyl)phenyl]ethyl}-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4-yl)benzoic acid (0.264 g, 0.491 mmol) was dissolved in 1 mL DMF. (1S)-1-(4-Pyridinyl)ethylamine (0.090 g, 0.736 mmol; prepared identically to its enantiomer, but starting with (R) α-methyl-1(4-pyridyl)methanol) was added followed by PyBOP (0.383 mg, 0.736 mmol). After 14 h, the reaction mixture was added to half-saturated NaCl solution and extracted with EtOAc (3×). The combined organic layers were washed with pH 4.0 phosphate buffer (2×), 5% NaHCO3, and brine and dried over Na2SO4. Purification on SiO2 (hexanes:EtOAc 20:80 to 0:100 to) provided the title compound as a white solid (0.153 g, 0.238 mmol, 48%): mp=158–160° C. 1H NMR (300 MHz, CDCl3) δ 8.62 (d, J=5.7 Hz, 2H), 7.86 (d, J=8.1 Hz, 2H), 7.57 (d, J=8.1 Hz, 2H), 7.49 (d, J=8.1 Hz, 2H), 7.37 (d, J=8.1 Hz, 2H), 7.33 (d, J=5.5 Hz, 2H), 6.52 (d, J=7.5 Hz, 1H), 5.33 (m, 1H), 4.75 (dd, J=10.3, 6.3 Hz, 1H), 4.06 (m, 2H), 3.75 (m, 1H), 3.41 (m, 1H), 3.22 (m, 4H), 2.52 (m, 1H), 2.40 (m, 2H), 1.63 (d, J=7.0 Hz, 3H), 1.40 (m, 1H), 0.97 (t, J=7.1 Hz, 3H) ppm. ESMS m/z 643 (M+H)+. Anal. calcd. for C36H33F3N4O4.½H2O: C, 66.35; H, 5.26; N, 8.60; found: C, 66.35; H, 5.42; N, 8.79.

1. customprepared identically to its enantiomer
2. additionwas added
3. extractionextracted with EtOAc (3×)
4. washThe combined organic layers were washed with pH 4.0 phosphate buffer (2×), 5% NaHCO3, and brine
5. dry with materialdried over Na2SO4
6. customPurification on SiO2 (hexanes:EtOAc 20:80 to 0:100 to)