1-(1-Methyl-4-piperidinyl)piperazine → 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-methoxy-7-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]quinoline-3-carbonitrile

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Following the procedure of Example 11, a mixture of 220 mg (0.5 mmol) of 4-[3-chloro-4-(1-methyl-1H-imidazole-2-ylsulfanyl)-phenylamino]-7-fluoro-6-methoxyquinoline-3-carbonitrile, 290 mg (1.6 mmol) of 1-(1-methylpiperidin-4-yl)piperazine in 1.2 mL of 1-methyl 2-pyrrolidinone is heated at 105° C. for 20 hours to yield the crude product. Purification by silica gel chromatography (gradient 9:1 methylene chloride/methanol to 85:15 methylene chloride/methanol) gives 210 mg of 4-({3-chloro-4-[(1-methyl-1H-imidazole-2-yl)thio]phenyl}amino)-6-methoxy-7-[4-(1-methylpiperidin-4-yl)piperazin-1-yl]quinoline-3-carbonitrile as a beige solid, mp 220-226° C. (shrinks at 205° C.).

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