Phosphorus oxychloride → N-(4,6-Dichloropyrido[3,2-d]pyrimidin-2-yl)acetamide

A mixture of 2-acetamido-6-chloro-pyrido[3,2-d]pyrimidin-4(3H)one (2.4 g, 10 mmol), N,N-diisopropylethylamine (5.4 ml, 30 mmol) and POCl3 (2.8 ml, 30 mmol) in dioxane (100 ml), was stirred at room temperature for 2 hours. After concentration under reduced pressure, the residue was redissolved in dichloromethane (200 ml) and extracted with cold water till pH 6-7. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to yield crude 2-acetamido-4,6-dichloro-pyrido[3,2-d]pyrimidine. This crude residue was dissolved in 1,4-dioxane (100 ml) and morpholine (5 ml) was added. The resulting reaction mixture was stirred at 50° C. for 1 hour. After concentration under reduced pressure, the residue was purified by silica gel flash chromatography, the mobile phase being a mixture of MeOH/dichloromethane (in a ratio of 1:40), resulting in the pure title compound as a yellowish solid (1.6 g, yield: 68%) which was characterised as follows:

1. concentrationAfter concentration under reduced pressure
2. dissolutionthe residue was redissolved in dichloromethane (200 ml)
3. extractionextracted with cold water till pH 6-7
4. dry with materialThe combined organic layers were dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure

ORD record

ord-3fe16988ad564112be74c92b65ef4abc

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08232278B2