Aniline → (S)-1-[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (4-hydroxy-phenyl)-amide

Participants

Reaction Steps

(S)-1-[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl]-pyrrolidine-2-carboxylic acid (see Example 5) (122 mg, 0.2 mmol) was dissolved in methylene chloride (2 mL) under a nitrogen atmosphere. HATU (121 mg, 0.3 mmol) and DIPEA (111 μL, 0.64 mmol) were added. The t-butyldimethylsilyl-(TBDMS-) protected aniline (71 mg, 0.3 mmol) was added and the reaction was stirred overnight. The solvent was evaporated and the resulting residue chromatographed over silica gel (gradient EtOAc/hexanes) to provide a white solid. The white solid was dissolved in methylene chloride (2 mL) and a 1.0 M solution in THF of tetrabutylammonium fluoride (TBAF) (1 mL) was added and the reaction stirred for 3 h. Water and a few drops of 1 N HCl were added and the layers separated. The organic layer was dried over sodium sulfate, filtered, and evaporated. The resulting residue was chromatographed over silica gel (25% EtOAc in methylene chloride) to provide 83 mg of the title compound as a white solid (M+1, 665.2).

Provenance & Evidence