2-[5-Bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-6-iodo-8-methyl-benzo[d][1,3]oxazin-4-one → 2-[3-bromo-1-(3-chloropyridin-2-yl)-1H-pyrazol-5-yl]-8-methyl-4-oxo-4H-3,1-benzoxazine-6-carbonitrile

To a solution of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazin-4-one (i.e. the benzoxazinone product of Step E) (600 mg, 1.1 mmol) in tetrahydrofuran (15 mL) was added copper(I) iodide (126 mg, 0.66 mmol), tetrakis(triphenyphosphine)palladium(0) (382 mg, 0.33 mmol) and copper(I) cyanide (800 mg, 8.8 mmol) sequentially at room temperature. The reaction mixture was then heated at reflux overnight. The reaction turned black in color, at which point thin layer chromatography on silica gel confirmed completion of the reaction. The reaction mixture was diluted with ethyl acetate (20 mL) and filtered through Celite®, followed by washing three times with 10% sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO4) and concentrated under reduced pressure to afford 440 mg of the title compound as a crude yellow solid.

1. temperatureThe reaction mixture was then heated
2. temperatureat reflux overnight
3. customThe reaction turned black in color, at which point thin layer chromatography on silica gel confirmed completion of the reaction
4. filtrationfiltered through Celite®
5. washby washing three times with 10% sodium bicarbonate solution
6. extractionThe organic extract
7. dry with materialwas dried (MgSO4)
8. concentrationconcentrated under reduced pressure

ORD record

ord-cbc2aefc348f4d5397a151f6e90deb04

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07875634B2