反应详情

To a solution of 6-[(R)-4-((S)-2,2-dimethyl-cyclopropanecarbonyl)-2-methyl-piperazin-1-yl]-nicotinic acid (6.4 mg, 0.020 mmol; Preparation 36) was added EDC (5.8 mg, 0.030 mmol) and HOAt (4.2 mg, 0.030 mmol) in DMA (0.5 mL, 5 mmol). The reaction mixture was stirred at RT for 30 min and then ((S)-1-{(S)-2-[4-(4′-amino-2,2′-difluoro-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (10 mg, 0.02 mmol; Preparation 38-B) and N,N-diisopropylethylamine (18 uL, 0.10 mmol) were added and the reaction mixture was stirred at RT overnight. The reaction mixture was concentrated by rotary evaporation, dissolved in 1:1 acetic acid:water (1.5 mL) and purified by reverse phase HPLC to provide the di-TFA salt of the title compound (6.8 mg). (m/z): [M+H]+ calcd for C43H50F2N8O5 797.39 found 797.4.

1. stirringthe reaction mixture was stirred at RT overnight
2. concentrationThe reaction mixture was concentrated by rotary evaporation
3. dissolutiondissolved in 1:1 acetic acid
4. customwater (1.5 mL) and purified by reverse phase HPLC