[NH2:1][C:2]1[C:3]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:4]=2[S:5][CH:6]=1.Cl.[Cl:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1.O>CN1CCCC1=O.CO.C(OCC)(=O)C>[ClH:16].[F:13][C:11]([F:14])([F:12])[C:9]1[CH:8]=[CH:7][C:4]2[S:5][CH:6]=[C:2]([NH:1][C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[C:3]=2[CH:10]=1A solution of 3-amino-5-trifluoromethylbenzo[b]thiophene (27 g, 124 mmol) and 4-chloropyridine hydrochloride (20.5 g, 137 mmol) in 250 mL of 1-methyl-2-pyrrolidinone was stirred at 70-80° C. for 1.5 hours. After cooling, the reaction mixture was stirred with water, washed with ether and separated. The aqueous layer was basified with a saturated sodium carbonate solution and the product which precipitated was collected. The reaction was repeated as above with an additional sample of 3-amino-5-trifluoromethylbenzo[b]thiophene (25.6 g, 118 mmol) and 4-chloropyridine hydrochloride (22 g, 148 mmol) in 225 mL of 1-methyl-2-pyrrolidinone. After a similar work-up, the two products were combined and dissolved in 10% methanol in ethyl acetate. The solution was dried (anhydrous magnesium sulfate), filtered and concentrated, yielding a yellow solid. This solid product was washed with ether and filtered to afford 39.1 g of a golden solid. Elution of a portion (3.5 g) of the residue through silica with ethyl acetate via flash column chromatography afforded 3.2 g of a white solid. Conversion of 2.4 g to the hydrochloride salt in 10% methanol in ether afforded 2.6 g of white crystals, mp 318-319° C.
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