Phenylacetyl chloride → {1-Cyclohexyl-2-[6-(6-fluoro-1H-indol-3-yl)-4-phenylacetyl-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution containing amine 50 (296 mg, 0.61 mmol) in DCM (8 mL) was cooled to 0° C. TEA (145 mg, 1.43 mmol) was added followed by phenylacetyl chloride (105 mg, 0.68 mmol) and the reaction mixture was warmed to ambient temperature. After 40 min, the reaction mixture was diluted with DCM and the resulting organic solution was washed successively with 1M HCl and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by flash silica gel chromatography (1:1 hexanes/EtOAc to 1:2 hexanes/EtOAc) to afford 244 mg (66%) of 56 as an off-white-colored foam. 1H NMR (300 MHz, CDCl3), mixture of amide rotamers: δ8.27 (s, 0.7H), 8.20 (s, 0.3H), 8.02 (dd, J=5.1, 8.4 Hz, 0.7H), 7.35-7.27 (m, 5H), 6.96-6.89 (m, 2H), 6.53 (s, 0.3H), 6.14 (s, 0.7H), 5.34 (d, J=9.3 Hz, 0.7H), 4.77 (d, J=5.1 Hz, 0.3H), 4.51-4.38 (m, 2H), 4.34-4.28 (m, 1H), 4.12 (app q, J=6.9 Hz, 1H), 4.04-3.89 (m, 2H), 3.77 (s, 1H), 3.51-3.42 (m, 0.7H), 3.30-3.20 (m, 0.3H), 2.60-2.53 (m, 1H), 1.76-1.63 (m, 6H), 1.44 (s, 9H), 1.19-1.05 (m, 5H) ppm. Mass spectrum, m/z [603.4] (M+H)+.

Provenance & Evidence