Sodium Bicarbonate → HCID 178502336, compound

Participants

Reaction Steps

To a solution of tert-butyl (2S)-2-[4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate (169 mg, 0.3847 mmol) (Ref. WO 2008/021923), methyl ((S)-1-((S)-2-(5-iodo-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate (180.9 mg, 0.3847 mmol) and Pd(dppf)Cl2—CH2Cl2 (47.13 mg, 0.05771 mmol) in acetonitrile (4 mL) in a sealed tube (25 mL) under nitrogen atmosphere is added aq. sodium bicarbonate (961.8 μL of 1 M, 0.9618 mmol). The resultant suspension is heated in oil bath at 100° C. for 16 hours, concentrated, diluted with water and CH2Cl2, organic solution is separated, aqueous solution is extracted with dichloromethane, combined extracts are washed with brine and dried (Na2SO4). Purification of the residue on 25+M biotage silica gel cartridge using MeOH-ethyl acetate (0:100 to 15:85) as eluent afforded tert-butyl (2S)-2-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]pyrrolidin-2-yl]-1H-benzimidazol-5-yl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carboxylate (101 mg, 0.1491 mmol, 38.75%) as light brown solid.

Provenance & Evidence