Toluene → 4-tert-butyl-N-{5-(4-methylphenyl)-6-[2-(4-(5-tetrazolyl)phenoxy)ethoxy]-pyrimidin-4-yl}benzensulfonamide

HRID 1082282

Reaction equation

HRID 1082282 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)=[C:19]([O:28][CH2:29][CH2:30][O:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=3)[N:18]=[CH:17][N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([Sn]([N:53]=[N+:54]=[N-:55])(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.[F-].[K+]>C(OCC)(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)=[C:19]([O:28][CH2:29][CH2:30][O:31][C:32]3[CH:33]=[CH:34][C:35]([C:38]4[NH:55][N:54]=[N:53][N:39]=4)=[CH:36][CH:37]=3)[N:18]=[CH:17][N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 1140TolueneHCID 522689Potassium FluorideHCID 4984872Tributyltin azideHCID 196895174-tert-butyl-N-{6-[2-(4-cyanophenoxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzensulfonamide

Product 1

HCID 1784182424-tert-butyl-N-{5-(4-methylphenyl)-6-[2-(4-(5-tetrazolyl)phenoxy)ethoxy]-pyrimidin-4-yl}benzensulfonamideYield 89.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-tert-butyl-N-{6-[2-(4-cyanophenoxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzensulfonamide (1.31 g), tributyltin azide (1.60 g) and toluene (13 ml) is refluxed under argon atmosphere for 24 hours. After cooling, ethyl acetate and 10% aqueous potassium fluoride solution are added to the reaction solution. The insoluble materials are removed by filtration, and the ethyl acetate layer is concentrated to dryness under reduced pressure. To the residue are added 10% aqueous sodium hydroxide solution and diethyl ether, and the mixture is stirred at room temperature for 20 minutes. The aqueous layer is washed with diethyl ether, and acidified with 10% hydrochloric acid under ice-cooling. The mixture 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: methanol=100: 0~20:1), and crystallized from ethyl acetate to give 4-tert-butyl-N-{5-(4-methylphenyl)-6-[2-(4-(5-tetrazolyl)phenoxy)ethoxy]-pyrimidin-4-yl}benzensulfonamide (1.26 g).

Workup

  1. temperatureis refluxed under argon atmosphere for 24 hours
  2. temperatureAfter cooling
  3. customThe insoluble materials are removed by filtration
  4. concentrationthe ethyl acetate layer is concentrated to dryness under reduced pressure
  5. additionTo the residue are added 10% aqueous sodium hydroxide solution and diethyl ether
  6. washThe aqueous layer is washed with diethyl ether
  7. temperaturecooling
  8. extractionThe mixture is extracted with ethyl acetate
  9. washthe ethyl acetate layer is washed
  10. customdried
  11. customevaporated
  12. customto remove the solvent
  13. customThe residue is purified by silica gel column chromatography (solvent: chloroform: methanol=100: 0~20:1)
  14. customcrystallized from ethyl acetate

Sources & evidence

ORD record
ord-bfd674b7ad3047618f3c549ead4ec4fa
Source dataset
uspto-grants-1996_12
Patent number
US05589478

Linked notes

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