Phosphorus oxychloride → 4,6-Dichloropyrido[3,2-d]pyrimidine

Temperature

110 °C

To a solution of 6-chloropyrido[3,2-d]pyrimidin-4(1H)-one (150 mg, 0.83 mmol) in POCl3 (2.0 mL) was added DIPEA (0.22 mL, 1.24 mmol) at room temperature. After stirring for 1 hour at 110° C., the reaction mixture was cooled to room temperature. The reaction mixture was concentrated in vacuo, and then diluted with water and extracted with dichlormethane. The combined organic layers were washed brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=10:1) to give 4,6-dichloropyrido[3,2-d]pyrimidine (120 mg, 73%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 7.87 (1H, d, J=8.8 Hz), 8.35 (1H, d, J=8.8 Hz), 9.14 (1H, s).

1. temperaturethe reaction mixture was cooled to room temperature
2. concentrationThe reaction mixture was concentrated in vacuo
3. additiondiluted with water
4. extractionextracted with dichlormethane
5. washThe combined organic layers were washed brine
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=10:1)

ORD record

ord-945117cee9f54b0fb6ba36e2514ab18b

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08664230B2