تفاعل #596302

معادلة التفاعل

3-chloro-4,6-difluorobenzenesulfonyl chloride

(2,4-dimethoxybenzyl)-pyrimidin-2-yl-amine

lithium(hexamethyldisilazane)

→

title compound

المردود 19.0%

5-Chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-pyrimidin-2-yl-benzenesulfonamide

المردود 19.0%

المذيبات

tetrahydrofuran

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةbefore cooling again to −78° C
2. 2
   درجة الحرارةAfter 30 minutes at this temperature the reaction was warmed to room temperature
3. 3
   أخرىThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution
4. 4
   استخلاصextracted into ethyl acetate
5. 5
   غسيلThe organic layer was washed with brine
6. 6
   تجفيفdried over magnesium sulfate
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىThe residue was purified
9. 9
   غسيلsilica gel column chromatography (50-100% dichloromethane in heptane gradient elution)

الإجراء التجريبي

A solution of (2,4-dimethoxybenzyl)-pyrimidin-2-yl-amine (Preparation 38, 736 mg, 3 mmol) in anhydrous tetrahydrofuran (20 mL) was cooled to −78° C. before the addition of lithium(hexamethyldisilazane) (1M solution in tetrahydrofuran, 3.30 mL, 3.30 mmol). The reaction was allowed to warm to 0° C. for 30 minutes before cooling again to −78° C. The resulting solution was added to a solution of 3-chloro-4,6-difluorobenzenesulfonyl chloride (890 mg, 3.6 mmol) in tetrahydrofuran (10 mL) at −78° C. After 30 minutes at this temperature the reaction was warmed to room temperature and stirred for 24 hours. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution and extracted into ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified using silica gel column chromatography (50-100% dichloromethane in heptane gradient elution) to afford the title compound as a white solid (260 mg, 19%).

المصدر