(S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate → (S)-2-(1-aminoethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide

Participants

Reaction Steps

A stirred solution of (S)-tert-butyl 1-(2-(cyclopropylamino)-3-(methylcarbamoyl)phenylamino)-1-oxopropan-2-ylcarbamate (1.1 g, 2.9 mmol) in AcOH (30 mL) was heated at 65° C. for 2 h, and cooled to rt. After concentrating under reduced pressure, the residue was subjected to 4 M HCl in 1,4-dioxane (20 mL) and stirred at rt for 40 min. The mixture was concentrated under reduced pressure and dissolved in water (5 mL) basified with 1 N NaOH to pH 9.5. The mixture was concentrated and triturated with MeOH-CDM (1:1). The crude product was purified by column chromatography on a silica gel column using DCM-MeOH—NH4OH (9:1:0.05) as eluent to give (S)-2-(1-aminoethyl)-1-cyclopropyl-N-methyl-1H-benzo[d]imidazole-7-carboxamide: 1H NMR (400 MHz, CDCl3) δ 7.80 (d, J=8 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 7.23 (dd, J=8, 8 Hz, 1H), 6.09 (br, 1H), 4.61 (t, J=8 Hz, 1H), 3.53-3.46 (m, 1H), 3.11 (d, J=4 Hz, 3H), 1.63 (d, J=8 Hz, 3H), 1.22-1.07 (m, 2H), 1.02-0.94 (m, 1H), 0.90-0.83 (m, 1H); LC-MS (ESI) m/z 259.1 [M+H]+.

Provenance & Evidence