CC1[O:11][C:10]2[C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3NCCC=2N=1.S(Cl)(Cl)=O.Cl.[F:21][C:22]([F:31])([F:30])[C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1.C([N:34]([CH2:37][CH3:38])CC)C>C1(C)C=CC=CC=1.ClCCl>[C:37]([C:38]1[CH:13]=[CH:12][C:9]([C:10]([NH:27][C:26]2[CH:28]=[CH:29][C:23]([C:22]([F:30])([F:31])[F:21])=[CH:24][CH:25]=2)=[O:11])=[CH:8][C:15]=1[CH3:14])#[N:34]
A mixture of 4-cyano-3-methyl-benzoic acid from Example E6 (750 mg, 4.6 mmol) and thionyl chloride (1.02 ml, 14.0 mmol) in toluene (40 ml) was heated at reflux for 2 h. After cooling at room temperature, solvents were re-moved in vacuo and azeotroped with toluene. The residue was redissolved in dichloromethane (25 ml) then 4-trifluoromethylaniline hydrochloride (1.11 g, 5.6 mmol) in dichloromethane (5 ml) and triethylamine (1.95 ml, 14.0 mmol) was added. The mixture was stirred at room temperature for 2 days, washed with brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel through an isolute (eluant; 20% EtOAc:80% cyclohexane) to yield the title compound (1.13 g, 80%).
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