Water → 3-(2-chlorophenyl)-7-methylthio-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one

To a stirred solution, cooled to 0° C., of 5-(2-chlorophenyl) aminomethyl-4-amino-2-methylthiopyrimidine (7.0 g, 24.9 mmol) in 200 mL of tetrahydrofuran was added triethylamine (10 mL, 71.7 mmol). This solution was then treated dropwise with a solution of phosgene (14.2 mL of 20% solution in toluene, 27.2 mmol). After stirring for 2 hours, an additional 5.0 mL of triethylamine (35.9 mmol) was added followed by phosgene (6.5 mL of 20% solution in toluene; 12.5 mmol). After stirring for an additional 2 hours, additional triethylamine (21n, 14.3 mmol) was added followed by phosgene (3 mL of 20% solution in toluene; 5.8 mmol). The reaction was stirred for one additional hour then warmed to room temperature, poured onto a heterogeneous solution of 75 mL water and 150 mL ethyl acetate. The mixture was then filtered and the phases separated. The aqueous phase was re-extracted twice with 150 mL ethyl acetate. The combined ethyl acetate extracts were concentrated under reduced pressure. The residue was stirred with ethyl acetate. The product was then collected by vacuum filtration and dried in vacuo to give 3.2 g of 3-(2-chlorophenyl)-7-methylthio-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (sulfide 10.1)as a white solid.

1. stirringAfter stirring for an additional 2 hours
2. stirringThe reaction was stirred for one additional hour
3. filtrationThe mixture was then filtered
4. customthe phases separated
5. extractionThe aqueous phase was re-extracted twice with 150 mL ethyl acetate
6. concentrationThe combined ethyl acetate extracts were concentrated under reduced pressure
7. stirringThe residue was stirred with ethyl acetate
8. filtrationThe product was then collected by vacuum filtration
9. customdried in vacuo

ORD record

ord-c0cf2081d4d14ffe8c40aafff922ebe4

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06451804B1