2,4,6-Trimethylpyridine → HCID 178502201, compound

Participants

Reaction Steps

To a mixture of methyl N-[2-methyl-1-[(2S,5S)-2-methyl-5-[4-[4-[4-[2-[(2S,5S)-5-methylpyrrolidin-2-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-benzimidazol-2-yl]pyrro-lidine-1-carbonyl]propyl]carbamate (88 mg, 0.126 mmol), (2S)-2-(methoxycarbonylamino)-3-methyl-butanoic acid (22 mg, 0.126 mmol) and 2,4,6-collidine (50.11 μl, 0.38 mmol) in DMF (3.5 ml) is added HATU (52.8 mg, 0.14 mmol) at 0° C. The reaction mixture is stirred at rt for 5 hours, diluted with EtOAc, washed with H2O and brine. The organic phase is dried over Na2SO4, filtered and concentrated. The residue is purified by flash column chromatography on silica gel (1 to 20% MeOH in CH2Cl2) and repurified by reverse phase HPLC using a gradient of CH3CN/water to afford the methyl N-[(1S)-1-[(2S,5S)-2-[4-[4-[4-[2-[(2S,5S)-1-[2-(methoxycarbonylamino)-3-methyl-butanoyl]-5-methyl-pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]-5-methyl-pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate (22 mg, 19.9%) as a white fluffy powder.

Provenance & Evidence