[C:1]([C:3]1[CH:4]=[C:5]([S:10]([NH:13][C:14]2[S:18][N:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[C:22]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([N:33]([CH3:35])[CH3:34])[CH:28]=2)[CH:21]=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O.[Cl-].[NH4+]>>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:8]2[CH:7]=[CH:6][C:5]([S:10]([NH:13][C:14]3[S:18][N:17]=[CH:16][N:15]=3)(=[O:12])=[O:11])=[CH:4][C:3]=2[C:1]#[N:2])=[C:22]([C:27]2[CH:32]=[CH:31][N:30]=[C:29]([N:33]([CH3:35])[CH3:34])[CH:28]=2)[CH:21]=13-Cyano-4-fluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (Preparation 65, 40 mg, 0.14 mmol), 4-chloro-2-[2-(dimethylamino)pyridin-4-yl]phenol (Preparation 865, 35.0 mg, 0.141 mmol) and potassium carbonate (58 mg, 0.42 mmol) in dimethyl sulfoxide (1 mL, 20 mmol) was stirred at 150° C. for 16 hours. The reaction mixture was cooled to ambient temperature and poured into saturated aqueous ammonium chloride. The aqueous layer was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in methylene chloride, concentrated onto diatomaceous earth, and purified by automated flash chromatography (12 g SiO2, hexanes to 20% methanol in ethyl acetate). The product-containing fractions were concentrated in vacuo then lyophilized from water and minimal acetonitrile to afford the product as a light yellow powder (40 mg, 60%).
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