N-Hydroxysuccinimide → (6R-trans)-1-chloro-N-[2-chloro-4-fluoro-5-(tetrahydro-6-hydroxy-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol-2(3H)-yl)phenyl]methanesulfonamide

Participants

Reaction Steps

To a stirred solution of the title compound of Step F (2.7 g, 5.4 mmol) and N-hydroxysuccinimide (0.621 g, 5.4 mmol) in acetonitrile (50 mL) was added a solution of N,N-dicyclohexylcarbodiimide (1.14 g, 5.4 mmol) in acetonitrile (30 mL) over 30 minutes at 0 to -5° C. The reaction was stirred at room temperature for 14 h. The by-products were removed by filtration and the solvent was evaporated under reduced pressure to yield the title compound of Step G (2.6 g, quantitative yield) as a crude product melting at 198-200° C. 1H NMR (Me2SO-d6) δ 10.2 (br s, 1H), 7.8-7.7 (d, 1H), 7.5-7.4 (d, 1H), 5.2-5.1 (br s, 1H), 5.1-5.0 (s, 2H), 4.5 (m, 1H), 4.34.2 (m, 1H), 3.1 (m, 1H), 2.3 (m, 1H), 2.0 (m, 1H).

Provenance & Evidence