Water → (R)-4-{5-[2-Chloro-4-(2-{(2S,4S)-1-[(S)-2-methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-4-methyl-pyrrolidin-2-yl}-3H-naphtho[1,2-d]imidazol-7-yl)-5-trifluoromethoxy-phenylcarbamoyl]-pyridin-2-yl}-3-methyl-piperazine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of [(S)-2-{(2S,4S)-4-methyl-2-[7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3H-naphth[1,2-d]imidazol-2-yl]-pyrrolidin-1-yl}-2-oxo-1-(tetrahydro-pyran-4-yl)-ethyl]-carbamic acid methyl ester (80 mg, 0.10 mmol; Preparation 23) and (R)-4-[5-(4-bromo-2-chloro-5-trifluoromethoxy-phenylcarbamoyl)-pyridin-2-yl]-3-methyl-piperazine-1-carboxylic acid tert-butyl ester (85 mg, 0.14 mmol) dissolved in toluene (0.92 mL) and water (0.34 mL) was added potassium carbonate (103 mg, 0.75 mmol). The reaction mixture was sparged under nitrogen and Pd(dppf)Cl2 CH2Cl2 (7.0 mg, 0.009 mmol) was added and the reaction mixture was heated to 90° C. overnight, cooled to RT, filtered through a combined pad of Celite® and silica gel and washed with EtOAc. The filtrate was washed with water and brine to produce a brownish colored solid, which was purified by silica chromatography (12 g column, 5-100% EtOAc/hexanes) to produce the title intermediate (89 mg, 60% yield) as a light colored solid. (m/z): [M+H]+ calcd for C48H54ClF3N8O8 963.37 found 963.5.

Provenance & Evidence