تفاعل #74641

معادلة التفاعل

4-aminopyrimidine

1,4-diazabicyclo[2.2.2]octane

5-chloro-2,4-difluorobenzenesulfonyl chloride

→

title compound

المردود 5.0%

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

المردود 5.0%

المذيبات

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction mixture immediately turned yellow and a precipitate formed
2. 2
   ترشيحthe reaction mixture was filtered
3. 3
   تركيزthe filtrate was concentrated in vacuo
4. 4
   أخرىto give a residue
5. 5
   أخرىThe residue was partitioned between 1M hydrochloric acid and ethyl acetate
6. 6
   أخرىThe organic phase was separated
7. 7
   تجفيفdried over anhydrous magnesium sulfate
8. 8
   تركيزconcentrated in vacuo
9. 9
   أخرىThe residue was partially purified by automated flash column chromatography
10. 10
    غسيلto 1% v/v acetic acid in ethyl acetate gradient elution
11. 11
    أخرىThe product was purified a second time by reverse phase HPLC

الإجراء التجريبي

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.

المصدر