HCID 58505549, compound → HCID 178471307, compound

Participants

Reaction Steps

To a stirred solution of ethyl 3-[7-(benzyloxy)-3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)indolizin-2-yl]-2,2-dimethylpropanoate (3.50 g, 6.10 mmol) in EtOH (50 mL) is added 10% Pd/C (480 mg). The suspension is stirred under an atmosphere of hydrogen for 1.5 h then filtered through a pad of diatomaceous earth and washed with EtOH. The filtrate is concentrated in vacuo to give ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-hydroxyindolizin-2-yl}-2,2-dimethylpropanoate (2.50 g, 85%). Also obtained is ethyl 3-[1-(2,2-dimethylpropanoyl)-7-hydroxy-3-(phenylcarbonyl)indolizin-2-yl]-2,2-dimethylpropanoate (0.28 g, 10%). A suspension of ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-hydroxyindolizin-2-yl}-2,2-dimethylpropanoate (100 mg, 0.207 mmol), 2-(chloromethyl)quinoline-HCl (66.0 mg, 0.310 mmol), and potassium carbonate (114 mg, 0.826 mmol) in DMF (3 mL) is stirred for 24 h at 23° C. The mixture is filtered and concentrated in vacuo to give ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-(quinolin-2-ylmethoxy)indolizin-2-yl}-2,2-dimethylpropanoate that is dissolved in THF (2 mL), MeOH (3 mL), and 6M aqueous NaOH (2 mL) and heated at 70° C. for 1 h then cooled to 23° C. and acidified to pH=1 with concentrated aqueous HCl. The mixture is partitioned between CH2Cl2 and brine then organics are dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by HPLC (25 to 75% CH3CN/0.1% TFA in water) gives the title compound (60 mg, 49%).

Provenance & Evidence