Diethyl (ethoxymethylene)malonate → Ethyl 1,6-dihydro-1-(2-methoxyethyl)-6-oxo-2-(3-thienyl)-5-pyrimidinecarboxylate

2-Methoxy-1-ethylamine (0.86 g, 11.4 mmol) was added to a solution of 3-thiophenecarboximidic acid ethyl ester hydrochloride (2.0 g, 10.4 mmol) in methanol (10 mL), which was then stirred at ambient temperature for 1.5 h. The reaction mixture was then concentrated under reduced pressure and redissolved in ethanol (10 mL). Sodium ethoxide solution (21% w/w in ethanol, 3.4 g, 10 mmol) and diethyl ethoxymethylenemalonate (2.2 g, 10 mmol) were added and the mixture was heated to reflux for 2 h before being concentrated under reduced pressure and purified by medium pressure liquid chromatography on silica gel eluting with 0 to 100% ethyl acetate in hexanes to provide 1.82 g of the title compound as an oil.

1. concentrationThe reaction mixture was then concentrated under reduced pressure
2. dissolutionredissolved in ethanol (10 mL)
3. temperaturethe mixture was heated
4. temperatureto reflux for 2 h
5. concentrationbefore being concentrated under reduced pressure
6. custompurified by medium pressure liquid chromatography on silica gel eluting with 0 to 100% ethyl acetate in hexanes

ORD record

ord-d91845cefe0e45499e0c913f8998aa7e

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952024B2