Ethyl Acetoacetate → Ethyl 4-amino-6-methylthieno[2,3-b]pyridine-5-carboxylate

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Reaction Steps

A mixture of 2-amino-3-thiophenecarbonitrile (2 g, 16.11 mmol), ethyl acetoacetate (2.24 mL, 17.72 mmol) and SnCl4 (3.78 mL, 32.2 mmol) in toluene (120 mL) was stirred at RT for 30 min and then at reflux for ca. 4 h. After cooling to RT, the mixture was quenched with 6M NaOH (ca. 80 mL), diluted with ethyl acetate (80 mL) and then filtered through celite. The organic layer of the filtrate was separated and the aqueous layer was re-extracted with ethyl acetate (50 mL×5). The combined organics were dried and concentrated. Purification by chromatography on silica, eluting with a gradient of 0-50% ethyl acetate in cyclohexane, to give the title compound (960 mg). LCMS (A) m/z: 237 [M+1]+, Rt 0.67 min (acidic).

Provenance & Evidence