Pivaloyl chloride → 1-(2-Bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethylpropan-1-one

Temperature

2.5 °C

To a slurry of 5-bromo-4,7-diazaindole (1.97 g, 9.95 mmol) in 40 mL of dichloromethane at 0-5° C. was added diethylaluminum chloride (1.0 M in hexane, 30 mL, 30 mmol). The reaction mixture was stirred at 0-5° C. for 30 min., then pivaloyl chloride (12 mL, 97 mmol) was added. The mixture was heated to reflux and stirred for 15 h, then cooled to 0-5° C. Sat. aq. NaHCO3 (40 mL) was carefully added, and the mixture was then partitioned between 300 mL of a sat. aq. NaCl solution and 300 mL of ethyl acetate. The mixture was filtered through a plug of celite and the layers were separated. The aqueous layer was extracted with 300 mL of ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated to a residue. Silica gel chromatography (20->60% EtOAc/hexanes) afforded 2.50 g (89%) of 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-propan-1-one as an off-white solid.

1. temperatureThe mixture was heated
2. temperatureto reflux
3. stirringstirred for 15 h
4. temperaturecooled to 0-5° C
5. customthe mixture was then partitioned between 300 mL of a sat. aq. NaCl solution and 300 mL of ethyl acetate
6. filtrationThe mixture was filtered through a plug of celite
7. customthe layers were separated
8. extractionThe aqueous layer was extracted with 300 mL of ethyl acetate
9. dry with materialThe combined organic layers were dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated to a residue

ORD record

ord-b32619941d774e2383575c3c769b2448

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07939531B2