Trifluoroacetic acid → HCID 178502413, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-tert-butyl 2-(5-(11-(2-((S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-7,8-dihydro-6H-dibenzo[f,h][1,5]dioxonin-3-yl)-4-chloro-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (2a, 0.05 g, 0.07 mmol) at 0° C. in DCM (1 ml) was added trifluoroacetic acid (0.17 g, 1.50 mmol). The reaction mixture was warmed to 25° C. and stirred for 2 hours after which all the volatiles were removed under reduced pressure. The contents were taken up in ACN (8 ml) and cooled to 0° C. after which diisopropylethyl amine (DIPEA) (0.06 g, 0.45 mmol), 1H-benzo-[d][1,2,3]-triazol-1-ol hydrate (0.03 g, 0.19 mmol) and EDCl (0.04 g, 0.19 mmol) were added. The reaction mixture was stirred for 10 minutes after which (S)-2-((methoxycarbonyl)-amino)-3-methylbutanoic acid (0.03 g, 0.19 mmol) was added. The reaction mixture was gradually warmed to 25° C. and stirred for 18 hr. The reaction mixture was evaporated to dryness followed by addition of crushed ice to precipitate solid product. The solid product was filtered and purified by preparative HPLC yielded an off-white solid (0.04 g, 40%) of methyl ((S)-1-((S)-2-(5-(11-(2-((S)-1-((S)-2-(methoxycarbonyl)amino-3-methylbutanoyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-7,8-dihydro-6H-dibenzo[f,h][1,5]dioxonin-3-yl)-4-chloro-1H-imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate. m/z 845.4 (M++1); 1H-NMR (400 MHz, CDCl3) δ (ppm): 7.67-7.20 (m, 7H), 5.26-5.43 (m, 2H), 4.42-4.27 (m, 6H), 3.85-3.58 (m, 10H), 3.14-2.97 (m, 2H), 2.37 (br m, 2H), 2.12-1.97 (m, 8H), 1.12-0.81 (m, 12H).

Provenance & Evidence