1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl (9aS)-4-[4-({[3-(1H-imidazol-1-yl)propyl]amino}carbonyl)phenyl]-5-oxo-2-{2-[4-(trifluoromethyl)phenyl]ethyl}-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

Participants

Reaction Steps

To a stirred solution of 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) Example 4C (0.050 g, 0.102 mmol) in 1 mL of dichloromethane, EDCI (0.023 g, 0.123 mmol) and 1-(3-aminopropyl)imidazole (0.026, 0.205 mmol)were added. The reaction mixture was allowed to stir for ˜3 h. The reaction mixture was concentrated and redissolved in 10 mL ethyl acetate. The organics were then washed with saturated aqueous NaHCO3 (2×) and brine. Filtration and concentration provided a brown oil which was purified by radial chromatography (dichloromethane/methanol (10:1)) to yield 0.013 g (20%) of the desired product as a tan solid: 1H NMR (CDCl3, 400 MHz) δ 7.89 (s, 2H), 7.52–7.50 (d, 2H, J=8.1), 7.39–7.37 (d, 2H, J=7.9), 7.32–7.29 (d, 2H, J=8.1), 7.89–6.89 (m, 2H), 4.73–4.70 (dd, 1H, J=6.4, J=10.3), 4.25 (bs, 2H), 4.04–3.92 (m, 2H), 3.72–3.60 (m, 1H), 3.52 (bs, 2H), 3.40–3.31 (m, 2H), 3.27–3.18(m, 4H), 2.51–2.41(m, 1H), 2.40–2.28 (m, 2H), 2.25–2.11 (m, 2H), 1.43–1.29 (m, 1H), 1.22 (s, 1H), 0.889–0.853 (t, 2H, J=7.2); low resolution MS (ES+) m/e 646 (MH+); TLC (CH2Cl2/MeOH (9:1)): Rf=0.24; 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, 96.6% purity.

Provenance & Evidence