Sodium ethoxide → 2-(trifluoromethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine

To a solution of the product from Step A (500 mg) in anhydrous ethanol (25 mL) was added sodium ethoxide (2.33 mL, 21% in ethanol). After stirring for 5 min, trifluoroacetamidine (700 mg) was added and the resulting mixture was heated to reflux for 1 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The organic layer was washed sequentially with 5% aqueous citric acid solution and brine, dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product which was deprotected by dissolving in 1N methanolic hydrogen chloride for 1 h. The resulting solution was concentrated and chromatographed on a Biotage® system (silica gel cartridge, gradient from 10% to 18% of 10% concentrated aqueous ammonium hydroxide in methanol/dichloromethane) to yield the title compound. LC-MS=190.0 (M+1).

1. temperaturethe resulting mixture was heated
2. temperatureto reflux for 1 h
3. washThe organic layer was washed sequentially with 5% aqueous citric acid solution and brine
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto give a crude product which
8. concentrationThe resulting solution was concentrated
9. customchromatographed on a Biotage® system (silica gel cartridge, gradient from 10% to 18% of 10% concentrated aqueous ammonium hydroxide in methanol/dichloromethane)

ORD-Eintrag

ord-52c5c92c93174736945227ebfe3afa60

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08653059B2