4-Methylmorpholine → 3-(Naphthalen-1-ylcarbamoyl)-hexahydro-pyrrolo[3,2-b]pyrrole-1,4-dicarboxylic acid 1-benzyl ester 4-tert-butyl ester

Participants

Reaction Steps

A solution of 36 (390 mg, 1.00 mmol) in NMP (5 mL) was cooled to 0° C. and treated with HATU (420 mg, 1.10 mmol) and NMM (0.17 mL, 1.50 mmol) followed in 15 min by the addition of 1-aminonaphthalene (145 mg, 1.00 mmol). The reaction mixture was allowed to warm to ambient temperature. After 3 h, the solution was diluted with EtOAc, washed with H2O, 1M HCl, H2O, sat NaHCO3, brine, dried over anhydrous Na2SO4, filtered and concentrated. Purification by reverse phase HPLC (2″ Dynamax® C18, 10-70% ACN in H2O with 0.1% HOAc over 30 min) afforded 53 (490 mg) as a white foam. 1H NMR (CDCl3, 300 MHz), ˜2:1 mixture of rotomers: δ8.32 (d, J=8.4 Hz, 1H), 8.15 (d, J=7.80 Hz, 1H), 7.84 (m, 1H), 7.64 (d, J=8.40 Hz, 1H), 7.42-7.56 (m, 4H), 7.26-7.42 (m, 4H), 5.17 (br s, 2H), 4.62 (m, 2H), 4.48 (dd, J=11.6, 2.5 Hz, 1H), 3.30-3.70 (m, 5H), 2.0-2.20 (m, 2H), 1.55 (s, 9H) ppm. Mass spectrum, m/z [516.1] (M+H)+.

Provenance & Evidence