Cesium carbonate → N-(3-(6-Methoxy-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-carboxamide

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In a 48-mL seal tube equipped with a magnetic stirring bar was placed N-(3-(5-Amino-6-methoxypyridin-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (17) (0.20 g, 0.5 mmol), 1-(6-chloro-pyridin-3-yl)-4-methyl-piperazine (0.11 g, 0.5 mmol), Pd2(dba)3 (0.046 g, 0.050 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.040 g, 0.070 mmol), and Cs2CO3 (0.33 g, 1.0 mmol) in dioxane (10 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane (10 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-33% MeOH in dichloromethane, to afford 0.140 g (50%) of N-(3-(6-Methoxy-5-(5-(4-methylpiperazin-1-yl)pyridin-2-ylamino)pyridine-3-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-carboxamide (18) as a solid.

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