Reaction #2366

Reaction equation

4-tert-butyl-N-{6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)pyrimidin-4-yl}benzenesulfonamide

sodium hydride

ammonium chloride

5-bromo-2-chloropyrimidine

→

N-[-6-{2-(5-bromopyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide

Yield 84.1%

Solvents

dimethylacetamide

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture is stirred at room temperature for 18 hours
2. 2
   Extractionextracted with ethyl acetate
3. 3
   WashThe ethyl acetate layer is washed
4. 4
   Otherdried
5. 5
   Otherevaporated
6. 6
   Otherto remove the solvent
7. 7
   OtherThe residue is purified by silica gel column chromatography (solvent; chloroform/methanol=40:1)
8. 8
   Otherto give crude crystals, which
9. 9
   Otherare recrystallized from ethyl acetate/diisopropyl ether

Procedure

To a solution of 4-tert-butyl-N-{6-(2-hydroxyethoxy)-5-(3-methoxyphenoxy)pyrimidin-4-yl}benzenesulfonamide (250 mg) in dimethylacetamide (5 ml) is added sodium hydride (60% dispersion-type, 64 mg) at room temperature, and the mixture is stirred for 20 minutes. To the reaction solution is added 5-bromo-2-chloropyrimidine (133 mg), and the mixture is stirred at room temperature for 18 hours. The reaction solution is poured into ice-water, and the mixture is neutralized with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/methanol=40:1) to give crude crystals, which are recrystallized from ethyl acetate/diisopropyl ether to give N-[-6-{2-(5-bromopyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (280 mg) as crystals.

Source