反应详情

A mixture of ((S)-1-{(S)-2-[4-(4′-amino-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (20 mg, 0.04 mmol) and p-nitrophenyl chloroformate (8.9 mg, 0.04 mmol) in DMA (5 mL) was stirred at RT for 30 min and then cyclopropyl-[4-((S)-2-methyl-piperazin-1-yl)-piperidin-1-yl]-methanone 2 HCl (18 mg, 0.06 mmol; Preparation 6) was added followed by DIPEA (32 μL, 0.18 mmol). The reaction mixture was stirred at RT for 1 h, concentrated, 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 product (6.8 mg, 20% yield) (m/z): [M+H]+ calcd for C42H53F3N8O6 823.40 found 823.6.

1. stirringThe reaction mixture was stirred at RT for 1 h
2. concentrationconcentrated
3. dissolutiondissolved in 1:1 acetic acid
4. customwater (1.5 mL), and purified by reverse phase HPLC