Phosphorus oxychloride → 4-Chloro-6-(trifluoromethyl)pyrido[3,2-d]pyrimidine

The title compound was prepared from trifluoromethyl-3H-pyrido[3,2-d]pyrimidin-4-one using the procedure described in Example 599, Step 2. A POCl3 (9.3 ml) suspension of 6-Trifluoromethyl-3H-pyrido[3,2-d]pyrimidin-4-one (1.0 g, 4.7 mmol) was heated at reflux for 4 hours, over which time the amber suspension became a clear, deep blue solution. The reaction was cooled to room temperature and concentrated under reduced pressure. The residue concentrated from dichloromethane 3× to remove residual POCl3. The residue was partitioned between 1:1 EtOAc and saturated sodium bicarbonate (28 ml). The mixture was stirred until visible gas evolution ceased. The suspension was filtered through a plug of celite. The layers of the filtrate were separated, and the organic phase was washed successively with saturated sodium bicarbonate and saturated sodium chloride, dried with magnesium sulfate and concentrated under reduced pressure to yield the semi-pure product as a purple solid. No further purification was carried out. The crude product was greater than 90% pure (as determined by analytical HPLC). MS: ES+ 234.11 (M+H, 100%

1. temperaturewas heated
2. temperatureat reflux for 4 hours, over which time the amber suspension
3. concentrationconcentrated under reduced pressure
4. concentrationThe residue concentrated from dichloromethane 3×
5. customto remove residual POCl3
6. customThe residue was partitioned between 1:1 EtOAc and saturated sodium bicarbonate (28 ml)
7. filtrationThe suspension was filtered through a plug of celite
8. customThe layers of the filtrate were separated
9. washthe organic phase was washed successively with saturated sodium bicarbonate and saturated sodium chloride
10. dry with materialdried with magnesium sulfate
11. concentrationconcentrated under reduced pressure

ORD record

ord-403df764d261436492f4f3d4379d14e5

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07601844B2