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-a3991cd13b7f41d192a0f4c24a998937

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07985861B2