Reaction #2395

Reaction equation

hydrochloric acid

4-(2-hydroxy-1,1-dimethylethyl)-N-{6-[2-hydroxyethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide

sodium hydride

5-bromo-2-chloropyrimidine

→

4-[2-(5-bromopyrimidin-2-yloxy)-1,1-dimethylethyl]-N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide

Yield 33.8%

Solvents

dimethylacetamide

THF

dimethylacetamide

tetrahydrofuran

Conditions

Workup

1. 1
   Extractionextracted with ethyl acetate
2. 2
   WashThe organic layer is washed with water and saturated 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=100:1)
7. 7
   Otherevaporated
8. 8
   Otherto remove the solvent
9. 9
   OtherThe resulting crude crystals are recrystallized from methylene chloride/isopropyl ether

Procedure

To a suspension of sodium hydride (65 mg) in dimethylacetamide (0.5 ml) and tetrahydrofuran (0.5 ml) is added dropwise a solution of 4-(2-hydroxy-1,1-dimethylethyl)-N-{6-[2-hydroxyethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (135 mg) in dimethylacetamide (2 ml) and THF (2 ml) solution over period of 5 minutes at room temperature, and thereto is added 5-bromo-2-chloropyrimidine (399 mg). The mixture is stirred at room temperature for 6 days. The reaction mixture is acidified with cold diluted hydrochloric acid, and extracted with ethyl acetate. The organic layer is washed with water and saturated brine, 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=100:1), and evaporated to remove the solvent. The resulting crude crystals are recrystallized from methylene chloride/isopropyl ether to give 4-[2-(5-bromopyrimidin-2-yloxy)-1,1-dimethylethyl]-N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (77 mg) as colorless crystals.

Source