反应详情

A DCM (5 mL, 0.7928 mmol) solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Preparation B; 250 mg, 0.7928 mmol) and DIEA (0.2071 mL, 1.189 mmol) was first cooled in an ice-water bath, then methyl 2-chloro-2-oxoacetate (0.07657 mL, 0.8325 mmol) was added to reaction drop-wise. Ice bath was removed and the reaction was stirred at ambient temperature for approx. 10 minutes to reach completion. The reaction was washed with 10% citric acid (aqueous). The aqueous layer was back-washed with DCM. The combined organic layer was washed with 1:1 water/brine, dried (Na2SO4) and concentrated. The crude oil residue was directly purified by silica chromatography, eluting with EtOAc/hexanes 1:1 to 2:1, yielding the final product as a pale-yellowish foamy powder (270 mg, 85% yield). MS (apci) m/z=402.2 (M+H).

1. customIce bath was removed
2. washThe reaction was washed with 10% citric acid (aqueous)
3. washThe aqueous layer was back-washed with DCM
4. washThe combined organic layer was washed with 1:1 water/brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated
7. customThe crude oil residue was directly purified by silica chromatography
8. washeluting with EtOAc/hexanes 1:1 to 2:1