1,2-Dichloroethane → {1-Cyclohexyl-2-[4-cyclopropanecarbonyl-6-(1,2,3,4-tetrahydro-naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrol-1-yl]-2-oxo-ethyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

A solution of 45 (563 mg, 1.21 mmol) in DCM (15 mL) was cooled to 0° C. and treated with R-(−)-tetrahydronaphthylamine (0.17 mL, 1.21 mmol), EDC (279 mg, 1.46 mmol), HOBt (197 mg, 1.46 mmol) and DIPEA (0.66 mL, 3.76 mmol), respectively. After 18 h, the solution was diluted with DCM, washed successively with 1M HCl, saturated aqueous NaHCO3, and brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by reverse phase HPLC (2″ Dynamax® C18, 20-100% ACN in H2O with 0.1% HOAc over 30 min) afforded 46 (430 mg) as a white foam. 1H NMR (CDCl3, 300 MHz), ˜1:1 mixture of rotomers: δ8.36 (d, J=8.4 Hz, 0.25H), 8.09 (d, J=8.7 Hz, 0.25H), 7.35 (d, J=9 Hz, 0.5H), 7.28-7.20 (m, 0.5H), 7.18-7.05 (m, 3.5H), 6.52 (d, J=8.4 Hz, 0.25H) 5.25-5.02 (m, 2H), 4.91-4.84 (m, 0.5H), 4.72-4.44 (m, 2H), 4.33-4.19 (m, 1.5H), 4.05-3.93 (m, 1H), 3.67-3.58 (m, 0.5H), 3.49-3.31 (m 1H), 3.15-2.98 (m, 1H), 2.86-2.71 (m, 2H), 2.44-2.35 (m, 1H), 1.98-1.54 (m, 10H), 1.44 (s, 5.5H), 1.17-0.75 (m, 15H) ppm. Mass spectrum, m/z [593.8] (M+H)+.

Provenance & Evidence