Thionyl Chloride → 4-tert-butyl-N-[6-{2-(5-ethylpyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide

HRID 2276Notes

Reaction equation

HRID 2276 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)=[C:19]([O:30][CH2:31][CH2:32][O:33][C:34]3[N:39]=[CH:38][C:37]([CH:40](O)[CH3:41])=[CH:36][N:35]=3)[N:18]=[CH:17][N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15]2[C:20]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=3)=[C:19]([O:30][CH2:31][CH2:32][O:33][C:34]3[N:35]=[CH:36][C:37]([CH2:40][CH3:41])=[CH:38][N:39]=3)[N:18]=[CH:17][N:16]=2)(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 196894724-tert-butyl-N-[6-{2-(5-(1-hydroxyethyl)pyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide

Product 1

HCID 196894794-tert-butyl-N-[6-{2-(5-ethylpyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamideYield 93.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-tert-butyl-N-[6-{2-(5-(1-hydroxyethyl)pyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide (150 mg) in methylene chloride (3 ml) is added thionyl chloride (90 mg), and the mixture is reacted at room temperature for 0.5 hour. The reaction solution is concentrated to dryness under reduced pressure, and to the residue are added 10% palladium-carbon (30 mg), triethylamine (76 mg) and ethanol (3 ml), and the mixture is stirred at room temperature for two hours under hydrogen atmosphere (1 atm). The catalyst is removed by filtration, and the filtrate is concentrated to dryness under reduced pressure. The residue is extracted with ethyl acetate, and the ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=10:1), and recrystallized from ethyl acetate/n-hexane to give 4-tert-butyl-N-[6-{2-(5-ethylpyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide (137 mg) as crystals.

Workup

  1. customthe mixture is reacted at room temperature for 0.5 hour
  2. concentrationThe reaction solution is concentrated to dryness under reduced pressure
  3. additionto the residue are added 10% palladium-carbon (30 mg), triethylamine (76 mg) and ethanol (3 ml)
  4. customThe catalyst is removed by filtration
  5. concentrationthe filtrate is concentrated to dryness under reduced pressure
  6. extractionThe residue is extracted with ethyl acetate
  7. washthe ethyl acetate layer is washed
  8. customdried
  9. customevaporated
  10. customto remove the solvent
  11. customThe residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=10:1)
  12. customrecrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-77ecea47c92b4de49601a091efcd4b91
Source dataset
uspto-grants-1998_03
Patent number
US05728706

Reaction notes

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