Anisole → 4-Bromo-6-(5-chloropyridin-2-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Phosphorus oxybromide (14 g, 49 mmol) was added portionwise over 2 min to a stirred suspension of 6-(5-chloropyridin-2-yl)-4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (3.36 g, 12.1 mmol), anisole (50 mL), and acetonitrile (50 mL) in a 250 mL flask. The stirred mixture clarified briefly and was then heated at reflux. The mixture was removed from the heat after 4.5 h. The cooled mixture was diluted with CH2Cl2 (100 mL), and poured onto a mixture of crushed ice (250 g) and 50% aqueous KOH (20 mL; 0.18 mol). The pH of the mixture was then adjusted to 12 with 2M aq. KOH, and extracted with CH2Cl2 (300 mL). The aqueous phase was diluted with brine (200 mL) and extracted with CH2Cl2 (2×100 mL). The combined CH2Cl2 layers were washed with saturated NaHCO3 (200 mL), dried (Na2SO4), filtered and concentrated to a brown oil which was purified by silica gel column (0-50% ethyl acetate/hexane) to give a yellow solid (1.48 g).

1. temperaturewas then heated
2. temperatureat reflux
3. customThe mixture was removed from the
4. temperatureheat after 4.5 h
5. additionThe cooled mixture was diluted with CH2Cl2 (100 mL)
6. extractionextracted with CH2Cl2 (300 mL)
7. additionThe aqueous phase was diluted with brine (200 mL)
8. extractionextracted with CH2Cl2 (2×100 mL)
9. washThe combined CH2Cl2 layers were washed with saturated NaHCO3 (200 mL)
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated to a brown oil which
13. customwas purified by silica gel column (0-50% ethyl acetate/hexane)

ORD-Eintrag

ord-85122ded8a664680833e6ea0cfabdff8

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08653091B2