反应详情

A mixture of (S)-(+)-2,2-dimethylcyclopropane carboxylic acid (2.09 mg, 0.018 mmol) and HATU (8.35 mg, 0.022 mmol) was stirred in DMA (1.0 mL, 11 mmol) for 10 min. and then ((S)-1-{(S)-2-[4-(5′-fluoro-4′-{[6-((R)-2-methyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2′-trifluoromethyl-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester tri-TFA (20.0 mg, 0.018 mmol, Preparation 41) and N,N-diisopropylethylamine (15.94 uL, 0.091 mmol) were added. The reaction mixture was stirred at RT overnight, concentrated by rotary evaporation, dissolved in 1:1 acetic acid:water (1.5 mL), filtered, and purified by preparative HPLC to provide the di-TFA salt of the title compound (4.8 mg). (m/z): [M+H]+ calcd for C44H50F4N8O5 847.38 found 847.4.

1. concentrationconcentrated by rotary evaporation
2. dissolutiondissolved in 1:1 acetic acid
3. filtrationwater (1.5 mL), filtered
4. custompurified by preparative HPLC