Dabco → 5-chloro-2,4-difluoro-N-pyrimidin-4-ylbenzenesulfonamide

A mixture of 4-aminopyrimidine (1.30 g, 13.7 mmol) and 1,4-diazabicyclo[2.2.2]octane (1.54 g, 13.7 mmol) were added concurrently to a solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (3.4 g, 14 mmol) in anhydrous acetonitrile (63 mL). The reaction mixture immediately turned yellow and a precipitate formed. The reaction mixture was stirred under argon. After 72 hours, the reaction mixture was filtered and the filtrate was concentrated in vacuo to give a residue. The residue was partitioned between 1M hydrochloric acid and ethyl acetate. The organic phase was separated, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was partially purified by automated flash column chromatography using an 80 g silica gel ISCO™ column using hexanes to 1% v/v acetic acid in ethyl acetate gradient elution. The product was purified a second time by reverse phase HPLC to give the title compound (193 mg, 5%) as a white solid.

1. customThe reaction mixture immediately turned yellow and a precipitate formed
2. filtrationthe reaction mixture was filtered
3. concentrationthe filtrate was concentrated in vacuo
4. customto give a residue
5. customThe residue was partitioned between 1M hydrochloric acid and ethyl acetate
6. customThe organic phase was separated
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated in vacuo
9. customThe residue was partially purified by automated flash column chromatography
10. washto 1% v/v acetic acid in ethyl acetate gradient elution
11. customThe product was purified a second time by reverse phase HPLC

ORD record

ord-965797111d304f09837b26e43868067d

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153814B2