Phosphorus oxychloride → 2,7-Dichloro-5-cyclopropyl-thiazolo[4,5-d]pyrimidine

To a solution of the compound (0.82 g) obtained in Step 4 in phosphorus oxychloride (2.5 ml) was added N,N-diisopropylethylamine (0.25 ml) under ice-cooling, and the mixture was heated under reflux for 2 hr. The reaction mixture was concentrated under reduced pressure, toluene was added to the residue, and the mixture was concentrated again under reduced pressure. The obtained residue was dissolved in ethyl acetate, poured into ice water and partitioned. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:8) to give the title compound (0.79 g).

1. temperaturecooling
2. temperaturethe mixture was heated
3. temperatureunder reflux for 2 hr
4. concentrationThe reaction mixture was concentrated under reduced pressure, toluene
5. additionwas added to the residue
6. concentrationthe mixture was concentrated again under reduced pressure
7. dissolutionThe obtained residue was dissolved in ethyl acetate
8. additionpoured into ice water
9. custompartitioned
10. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationfiltrated
13. concentrationconcentrated under reduced pressure
14. customThe residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:8)

ORD record

ord-964db4f1b44c4406afb175ce02e30b31

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08017612B2