Ethyl Acetoacetate → Ethyl 4-amino-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate

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Reaction Steps

A mixture of 2-amino-4-[3-(methyloxy)phenyl]-3-thiophenecarbonitrile (1 g, 4.34 mmol) (Description 13), ethyl acetoacetate (0.550 mL, 4.34 mmol) and SnCl4 (1.019 mL, 8.68 mmol) in toluene (25 mL) was stirred at RT for 30 min followed by reflux for 3 h. After cooling to RT, the mixture was quenched with 2M NaOH (50 mL) and extracted with ethyl acetate (3×40 mL). The combined organics were washed with brine (50 mL), dried and concentrated. Purification by chromatography on silica gel, eluting with a gradient of 0-50% ethyl acetate in cyclohexane, to give the title compound (915 mg). LCMS (A) m/z: 343 [M+1]+, Rt 1.25 min (acidic).

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