Oxalyl chloride → 4-Chloropyrido(3,2-d)pyrimidine

To a stirred solution pyrido[3,2-d]pyrimidin-4-ol (B-2) (16 g, 109 mmol, 1.0 eq) in DCM (200 mL) and DMF (0.4 mL) at RT, oxalyl chloride (23.2 mL, 272 mmol, 2.5 eq) is added dropwise (over 5 min) and the resulting mixture is stirred at reflux overnight. The mixture is allowed to cool to RT and concentrated in vacuo. The residue is diluted with water (200 mL), neutralized with saturated aqueous NaHCO3 solution below 10° C. to adjust the pH to 8-9 and then extracted with ethyl acetate (4×100 mL). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo. The residue is purified by flash column chromatography on silica gel (16-50% ethyl acetate-petroleum ether) to afford the product, 4-chloropyrido[3,2-d]pyrimidine (B-3).

1. temperatureat reflux overnight
2. concentrationconcentrated in vacuo
3. additionThe residue is diluted with water (200 mL)
4. customneutralized with saturated aqueous NaHCO3 solution below 10° C.
5. extractionextracted with ethyl acetate (4×100 mL)
6. washThe combined organic layers are washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationThe filtrate is concentrated in vacuo
10. customThe residue is purified by flash column chromatography on silica gel (16-50% ethyl acetate-petroleum ether)

ORD record

ord-27b981e075a24f41924d913cea149013

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09388183B2