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

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Reaction Steps

To a solution of 2-amino-5-methyl-3-thiophenecarbonitrile (5 g, 36.2 mmol), ethyl 3-oxobutanoate (5.49 mL, 43.4 mmol) in toluene (200 mL) was added SnCl4 (5.10 mL, 43.4 mmol). The resulting mixture was refluxed for 2 h after which the heater was switched off. SnCl4 (2.123 mL, 18.09 mmol) was added and the mixture refluxed for another 4 h. The solution was cooled and aqueous NaOH (5M) was added until the solution turned basic. Ethyl acetate (100 mL) was added and washed with water (3×30 mL). The organic layer was dried over MgSO4, filtered and solvent removed in vacuo. Purification by chromatography on silica gel, eluting with a gradient of 0-50% ethyl acetate in cyclohexane afforded the title compound (6.48 g). LCMS (A) m/z: 251 [M+1]+, Rt 0.74 min (acidic).

Provenance & Evidence