Diisopropylethylamine → 4-{2-[2-(Benzyloxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-3-phenoxy-hexahydro-pyrrolo[3,2-b]pyrrole-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution containing Cbz-N(Me)Ala-OH (196 mg, 0.83 mmol) and crude 15 (307 mg, 0.76 mmol) in anhydrous NMP (3 mL) was cooled to 0° C. HATU (315 mg, 0.83 mmol) and DIPEA (118 mg, 0.91 mmol) were added and the reaction mixture was slowly warmed to ambient temperature. After 16 h, the reaction mixture was diluted with diethyl ether and EtOAc (1:4) and washed successively with 1M HCl, aqueous NaHCO3, water, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 420 mg (88%) of crude 16 which was used without further purification. 1H NMR (CDCl3, 300 MHz), mixture of rotomers: δ7.37-7.25 (m, 9H), 6.96 (m, 1H), 6.69 (br s, 1H), 5.19 (m, 2H), 4.91 (m, 1H), 4.81 (m, 1H), 4.58-4.46 (m, 2H), 4.04 (m, 2H), 3.97 (app d, J=12.6 Hz, 0.5H), 3.84 (app d, J=12.6 Hz, 0.5H), 3.40-3.25 (m, 2H), 2.88 (s, 3H), 2.48 (dd, J=5.7, 13.5 Hz, 0.5H), 2.33 (dd, J=5.4, 12.9 Hz, 0.5H), 2.06-1.82 (m, 2H), 1.51 (s, 4.5H), 1.49 (s, 4.5H), 1.36 (d, J=6.9 Hz, 3H), 0.91 (dd, J=2.7, 6.6 Hz, 3H), 0.83 (dd, J=1.8, 6.9 Hz, 3H) ppm.

Provenance & Evidence