反应详情

A suspension of 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.100 g, 0.167 mmol), [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.046 g, 0.218 mmol), N,N-diisopropylethylamine (0.088 mL, 0.502 mmol), and propylphosphonic anhydride (0.128 mL of a 50% solution in ethyl acetate, 0.218 mmol) in dichloromethane (2.57 mL) was stirred at room temperature for 30 min. Water (2 mL) was added, and the mixture was poured into a hydrophobic frit to separate the layers. The organic phase was concentrated in vacuo, and the residue was loaded onto florisil and purified via column chromatography (ISCO, 4 g silica, 0-10% methanol/methylene chloride) to afford 3-{[4-(3,3-difluoro-1-pyrrolidinyl)-1-piperidinyl]methyl}-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.110 g, 83% yield). MS (m/z) 755.2 (M+H+).

1. additionthe mixture was poured into a hydrophobic frit
2. customto separate the layers
3. concentrationThe organic phase was concentrated in vacuo
4. custompurified via column chromatography (ISCO, 4 g silica, 0-10% methanol/methylene chloride)