Reaction #2396

Reaction equation

hydrochloric acid

4-tert-butyl-N-{6-[2-(5-hydroxypyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide

potassium carbonate

5-bromo-2-chloropyrimidine

→

4-tert-butyl-N-{6-[2-(5-(5-bromopyrimidin-2-yloxy)pyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide

Yield 92.0%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   Extractionextracted with ethyl acetate
2. 2
   WashThe organic layer is washed with water and brine
3. 3
   Dryingdried over anhydrous sodium sulfate
4. 4
   Otherevaporated
5. 5
   Otherto remove the solvent
6. 6
   OtherThe oily residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=50:1)
7. 7
   Otherthe fractions are evaporated
8. 8
   Otherto remove the solvent
9. 9
   OtherThe resulting crude crystals are recrystallized from methylene chloride/isopropyl ether

Procedure

To a solution of 4-tert-butyl-N-{6-[2-(5-hydroxypyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (200 mg) in dimethylformamide (4 ml)is added potassium carbonate (154 mg), 5-bromo-2-chloropyrimidine (216 mg), and the mixture is stirred at 50° C. for two hours. The reaction mixture is acdified with cold hydrochloric acid, and extracted with ethyl acetate. The organic layer is washed with water and brine, and dried over anhydrous sodium sulfate, and evaporated to remove the solvent. The oily residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=50:1), and the fractions are evaporated to remove the solvent. The resulting crude crystals are recrystallized from methylene chloride/isopropyl ether to give 4-tert-butyl-N-{6-[2-(5-(5-bromopyrimidin-2-yloxy)pyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (238 mg) as colorless needles.

Source