Diisopropylethylamine → {1-[4-Cyclopentyl-6-(6-fluoro-1H-indol-3-yl)-hexahydro-pyrrolo[3,2-b]pyrrole-1-carbonyl]-2,2-dimethyl-propyl}-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution containing Boc-L-Tle-OH (160 mg, 0.7 mmol) in anhydrous NMP (4 mL) was cooled to 0° C. HATU (264 mg, 0.7 mmol) and DIPEA (148 mg, 0.7 mmol) were added followed by the addition of crude 37 (220 mg, 0.7 mmol) in anhydrous NMP (5 mL). The reaction mixture was slowly warmed to ambient temperature. After 4 h, the reaction mixture was diluted with EtOAc and washed successively with aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude product was purified by silica gel HPLC (2″ Dynamax SiO2, 20-100% EtOAc/hexanes over 30 min; Flow: 40 mL/min) to afford 280 mg (66%, 2 steps) of 38. 1H NMR (CDCl3, 300 MHz): δ8.37 (s, 1H), 7.58 (dd, J=5.7, 8.4 Hz, 1H), 7.12 (s, 1H), 6.73 (dd, J=1.8, 9.6 Hz, 1H), 6.65-6.58 (m, 1H), 5.07 (d, J=9.3 Hz, 1H), 4.76 (app t, J=8.4 Hz, 1H), 3.76 (d, J=9.3 Hz, 1H), 3.69 (app t, J=7.2 Hz, 1H), 3.41 (app t, J=8.7 Hz, 1H), 3.09 (app t, J=6.9 Hz, 1H), 3.00-2.94 (m, 2H), 2.66-2.50 (m, 2H), 1.69-1.51 (m, 5H), 1.39 (m, 3H), 1.18 (s, 9H), 0.01 (s, 9H) ppm. Mass spectrum, m/z [527.4] (M+H)+.

Provenance & Evidence