Isopropyl chloroformate → benzofuran-5-yl-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N,N-dimethylethanamide

Participants

Reaction Steps

To a solution of (2R)-[(tert-butoxycarbonyl)amino](2,3-dihydro-1H-inden-2-yl)ethanoic acid (419 mg) in dry tetrahydrofuran (5 ml) at −20° C. under a nitrogen atmosphere was added N-methylmorpholine (158 μl) and a solution of isopropylchloroformate in toluene (1.0M, 1.44 ml). After 10 minutes, a solution of N-[1-(benzofuran-5-yl)-2-(dimethylamino)-2-oxoethyl]-L-leucine (478 mg) in dimethylformamide (5 ml) was added and the reaction was allowed to warm to room temperature. After 20 hours, the solvent was removed in vacuo and the residue was dissolved in 4N hydrochloric acid in dioxan (4 ml). After 4 hours methanol (13 ml) was added and the reaction was left to stand for a further 18 hours. The solvent was then removed in vacuo and the residue was separated between dichloromethane and saturated sodium bicarbonate solution. The organic phase was evaporated in vacuo and the residue was applied to an SPE (10 g, silica). The product was eluted using an ethyl acetate:methanol gradient (3:1 to 1:3) to afford (2R)-2-(benzofuran-5-yl-2-[(3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl]-N,N-dimethylethanamide (51 mg).

Provenance & Evidence