N,N-Diethylaniline → 7-Chloro-2,5-dimethylpyrazolo(1,5-a)pyrimidine

Temperature

22 °C

Add 2,5-dimethylpyrazolo[1,5-a]pyrimidin-7-one (20 g, 122 mmol) to 1,4-dioxane (60 mL). Stir the mixture at 22° C. for 10 min and then add N,N-diethylaniline (20.8 mL, 128 mmol). Stir for an additional 5 min and then add phosphorus oxychloride (11.7 mL, 126 mmol) over 15 min. Stir the mixture at 22° C. for 15 min, then heat to 80-85° C. over 35 min and hold the reaction at this temperature for 1.5 h. Add the cooled reaction mixture slowly to a solution of potassium phosphate dibasic (106.7 g, 612.82 mmol) in water (325 mL) cooled to 0-5° C., keeping the temperature below 5° C. during the addition. Stir the mixture at 22° C. and then add methyl-t-butyl ether (150 mL). Separate the organic layer and extract the aqueous layer with methyl-t-butyl ether (2×100 mL). Combine the organic portions, dry over sodium sulfate, filter, and evaporate the solvent. Purify by silica gel chromatography, eluting with hexanes/ethyl acetate (2/1) to provide the title compound as a yellow solid (20.7 g, 88%). ES/MS m/z (35Cl) 182 (M+1)+.

1. stirringStir for an additional 5 min
2. stirringStir the mixture at 22° C. for 15 min
3. temperatureheat to 80-85° C. over 35 min
4. customthe reaction at this temperature for 1.5 h
5. additionAdd
6. temperaturecooled to 0-5° C.
7. customthe temperature below 5° C.
8. additionduring the addition
9. stirringStir the mixture at 22° C.
10. customSeparate the organic layer
11. extractionextract the aqueous layer with methyl-t-butyl ether (2×100 mL)
12. dry with materialCombine the organic portions, dry over sodium sulfate
13. filtrationfilter
14. customevaporate the solvent
15. customPurify by silica gel chromatography
16. washeluting with hexanes/ethyl acetate (2/1)

ORD record

ord-119eea6d023f466ca8f60e9425591abd

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08030304B2