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

Temperature

110 °C

Huning's base (1.18 mL, 6.77 mmol) was added to a solution of 6-chloropyrido[3,2-d]pyrimidin-4(3H)-one (820 mg, 4.52 mmol) in POCl3 (8.42 mL, 90.0 mmol) at room temperature, and the reaction mixture was heated at 110° C. for 5 h. After cooled to room temperature, the excess POCl3 was removed by evaporation. Toluene was added to the residue, and the azeotrope was removed under reduced pressure. DCM was poured into the residue, and the suspension was treated carefully with aq. NaHCO3 at 0° C. to pH 7˜9. The insoluble solid was filtered off, and the filtrate was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (DCM:EtOAc=10:1) to give 4,6-dichloropyrido[3,2-d]pyrimidine (780 mg, 86%) as a pale yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 7.86 (1H, d, J=8.8 Hz), 8.34 (1H, d, J=8.8 Hz), 9.14 (1H, s). m/z=199.01 [M+1]+.

1. temperatureAfter cooled to room temperature
2. customthe excess POCl3 was removed by evaporation
3. additionToluene was added to the residue
4. customthe azeotrope was removed under reduced pressure
5. additionDCM was poured into the residue
6. additionthe suspension was treated carefully with aq. NaHCO3 at 0° C. to pH 7˜9
7. filtrationThe insoluble solid was filtered off
8. extractionthe filtrate was extracted with DCM
9. dry with materialThe combined organic layers were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by column chromatography (DCM:EtOAc=10:1)

ORD record

ord-fa12cd1855924ae6855e592ead6d410b

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422298B2