反应详情

5-Methyl-6-[(methyloxy)methyl]-4-pyrimidinol (Intermediate 48, 2.10 g, 13.62 mmol) was dissolved in DCM (20 ml), treated with phosphorus oxychloride (12.04 ml, 129 mmol) and the resulting mixture was heated under reflux for 3 hours, allowed to cool to room temperature and left to stand overnight. The solvent was removed under reduced pressure, the residue taken up in ice water and the pH was adjusted to 7 using aqueous 2M sodium hydroxide solution. The mixture was extracted with chloroform (×3) and the chloroform layers were separated, combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by SP4 Biotage column chromatography eluting with a gradient of 0-50% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a yellow oil (2.14 g);

1. temperaturethe resulting mixture was heated
2. temperatureunder reflux for 3 hours
3. waitleft
4. customThe solvent was removed under reduced pressure
5. extractionThe mixture was extracted with chloroform (×3)
6. customthe chloroform layers were separated
7. customdried under magnesium sulfate
8. customevaporated under reduced pressure
9. customThe residue was purified by SP4 Biotage column chromatography
10. washeluting with a gradient of 0-50% ethyl acetate and iso-hexane
11. additionProduct containing fractions
12. customevaporated under reduced pressure