反应详情

2-[4-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-1-piperazin yl]-4-thiazolecarboxylic acid (200 mg, 0.5 mmol) (i.e. the product of Example 30, Step D) was suspended in 5 mL of dry dichloromethane and treated with triethylamine (150 μl, 1.08 mmol) to give a homogeneous solution. To this reaction mixture was added O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU, 210 mg, 0.55 mmol) followed by (1R)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (106 mg, 0.60 mmol) (i.e. the product of Example 6, Step A). The reaction mixture was stirred at ambient temperature for 3 h, passed through a Varian Chem Elut™ CE1010 column pretreated with 5 mL of 20% aqueous citric acid solution. The column was flushed with three column volumes of dichloromethane, concentrated and purified by silica gel chromatography eluting with ethyl acetate to give 223 mg of the title product, the compound of present invention as white foam.

1. customto give a homogeneous solution
2. customThe column was flushed with three column volumes of dichloromethane
3. concentrationconcentrated
4. custompurified by silica gel chromatography
5. washeluting with ethyl acetate