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

Alternatively, a mixture of 2-amino-3-thiophenecarbonitrile (2.5 g, 20.13 mmol), ethyl 3-oxobutanoate (2.80 mL, 22.15 mmol) and SnCl4 (4.73 mL, 40.3 mmol) in toluene (135 mL) was stirred at RT for 30 min, and then refluxed for 2 h. The mixture was then basified with 6M NaOH (ca. 25 mL), diluted with 10% MeOH in DCM (40 mL), and the mixture filtered through celite. The organic layer of the filtrate was then separated and the aqueous layer re-extracted with 10% MeOH in DCM (50 mL×3). The combined organic layers were dried and concentrated. The residue was then purified by chromatography on silica, eluting with a gradient of 0-10% ethyl acetate in DCM, to give the title compound. Another batch of 2-amino-3-thiophenecarbonitrile (2.5 g, 20.13 mmol) was subjected to the same procedure and the products from each reaction were combined to give the title compound (2.36 g).

1. temperaturerefluxed for 2 h
2. filtrationthe mixture filtered through celite
3. customThe organic layer of the filtrate was then separated
4. extractionthe aqueous layer re-extracted with 10% MeOH in DCM (50 mL×3)
5. customThe combined organic layers were dried
6. concentrationconcentrated
7. customThe residue was then purified by chromatography on silica
8. washeluting with a gradient of 0-10% ethyl acetate in DCM

ORD record

ord-276dbf979b2348b1874b6a09f80016cd

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09029545B2