5-(4-Fluorophenyl)cyclohexane-1,3-dione → 4-[(3aS)-6-(4-Fluorophenyl)-8,10-dioxo-2,3,3a,5,6,7,8,10-octahydro-1H-pyrrolizino[1,2-b]quinolin-9-yl]-N-[(1R)-2,3-dihydro-1H-inden-1-yl]benzamide

Participants

Reaction Steps

Using the synthetic method described earlier in the synthesis of 4-{(9aS)-3-acetyl-2-[2-(4-fluorophenyl)ethyl]-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4-yl}-N-(2-furylmethyl)benzamide (Example 29), the title compound was prepared from 4-[(3aS)-6-(4-fluorophenyl)-8,10-dioxo-2,3,3a,5,6,7,8,10-octahydro-1H-pyrrolizino[1,2-b]quinolin-9-yl]benzoic acid (prepared using the enamine of 5-(4-fluorophenyl)-1,3-cyclohexanedione and Knoevenagel product 4-[(1Z)-3-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]-2-(ethoxy-carbonyl)-3-oxo-1-propenyl]benzoic acid). A portion of the crude material (100 mg) was chromatographed (silica gel/ethyl acetate) to give the title compound as a tan powder (52 mg, 52%). LCMS m/z 572 (MH+) 1H NMR (300 MHz, DMSO-d6) δ 7.90 (d, 2H), 7.40 (m, 2H), 7.10–7.35 (m, 6H), 7.10 (dd, 2H), 6.40 (d, 1H), 5.75 (m, 2H), 4.75 (d, 1H), 3.30–3.75 (m, 2H), 2.80–3.10 (m, 2H), 2.70 (m, 1H), 2.55 (m, 1H), 2.35 (m, 1H), 1.95 (m, 1H), 1.75 (m, 4H), 1.50 (m, 2H) ppm.

Provenance & Evidence