1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl (9aS)-2-(2,4-difluorobenzyl)-4-{4-[(2,3-dihydro-1H-indol-1-ylamino)carbonyl]phenyl}-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

Participants

Reaction Steps

To a stirred solution of 4-[(9aS)-2-(2,4-difluorobenzyl)-3-(ethoxycarbonyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4-yl]benzoic acid (0.150 g, 0.305 mmol) in 2 mL of dichloromethane, EDCI (0.070 g, 0.365 mmol), HOBT (0.049 g, 0.365 mmol) and 1-indolinamine (ref. Wijngaarden, I. et. al., J Med Chem, 1993, 36, 3693–99) (0.082 g, 0.609 mmol) were added. The reaction mixture was allowed to stir for ˜3 h. The reaction mixture was concentrated and redissolved in 1 mL of ethyl acetate. The organics were then washed with saturated aqueous NaHCO3 and brine. Filtration and concentration provided a brown oil which was purified by radial chromatography (dichloromethane/methanol (10:1)) to yield 0.071 g (38%) of the desired product as a tan solid: 1H NMR (CDCl3, 400 MHz) δ 7.90–7.85 (d, 2H, J=8.27), 7.53–7.45 (m, 2H), 7.23–7.11 (m, 3H), 6.83–6.73 (m, 2H), 4.74–4.67 (dd, 1H, J=10.5, J=6.38), 4.42–4.23 (q, 2H, J=15.34), 3.99–3.90 (m, 2H), 3.74–3.65 (m, 3H), 3.40–3.32 (m, 1H), 3.14–3.06 (m, 2H), 2.50–2.42 (m, 1H ), 2.37–2.26 (m, 2H), 1.70–1.50 (m, 3H), 1.46–1.31 (m, 1H), 0.95–0.84 (t, 3H, J=7.24); low resolution MS (ES+) m/e 609 (MH+); RP-HPLC (BDS Hypersil C-18 25 cm×4.6 mm; 10–100% CH3CN in H2O with 0.1% TFA buffer; 30 minutes; 1 mL/min) tr=8.12 min, 93.3% purity.

Provenance & Evidence