1-Hydroxybenzotriazole → methyl 1-(1-((tert-butoxycarbonyl)amino)cyclopropanecarboxamido)-3-chloro-1H-pyrrole-2-carboxylate

Participants

Reaction Steps

To a stirred solution of methyl 1-amino-3-chloro-1H-pyrrole-2-carboxylate (1.50 g, 8.59 mmol) in DCM (50 mL) was added 1-((tert-butoxycarbonyl)amino) cyclopropanecarboxylic acid (2.59 g, 12.9 mmol), HOBT (1.58 g, 10.3 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimidehydrochloride (2.47 g, 12.9 mmol) and DIPEA (3.00 mL, 17.2 mmol) at room temperature. The reaction mixture was stirred at room temperature for 12 h then concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL) and washed with water (2×30 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by CombiFlash ISCO (REDISEP®, SiO2, 12 g, 50% EtOAc/petroleum ether) to give methyl 1-(1-((tert-butoxycarbonyl)amino)cyclopropanecarboxamido)-3-chloro-1H-pyrrole-2-carboxylate (950 mg, 30.9%) as a white solid. LCMS Condition B-16: retention time 0.87 min, [M+1]=358.1. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.01-1.06 (m, 2H), 1.30-1.38 (m, 2H), 1.41 (s, 9H), 3.74 (s, 3H), 6.27 (s, 1H), 6.99 (d, J=2.4 Hz, 1H), 7.46 (d, J=2.4 Hz, 1H), 11.08 (s, 1H).

Provenance & Evidence