1,4-Dioxane → 4-tert-butyl-N-[6-{2-(5-(2-thienyl)pyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]benzenesulfonamide

HRID 2292

Reaction equation

HRID 2292 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[N:37]=[CH:36][C:35](Br)=[CH:34][N:33]=3)[N:18]=[C:17]([CH2:39][CH2:40][CH3:41])[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[Sn](CCCC)(CCCC)CCCC.O1CCOCC1.[F-].[K+]>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[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[N:37]=[CH:36][C:35]([C:43]4[S:42][CH:46]=[CH:45][CH:44]=4)=[CH:34][N:33]=3)[N:18]=[C:17]([CH2:39][CH2:40][CH3:41])[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 522689Potassium FluorideHCID 27793732-(Tri-n-butylstannyl)thiopheneHCID 19689505N-{6-[2-(5-Bromo-pyrimidin-2-yloxy)-ethoxy]-2-propyl-5-p-tolyl-pyrimidin-4-yl}-4-tert-butyl-benzenesulfonamide

Product 1

HCID 196895274-tert-butyl-N-[6-{2-(5-(2-thienyl)pyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]benzenesulfonamideYield 69.3%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-tert-butyl-N-[6-{2-(5-bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]benzenesulfonamide (300 mg), 2-thienyltributyltin (670 mg), bis(triphenylphosphine)palladium (II) chloride (16 mg) and dioxane (5 ml) is refluxed for 80 minutes. After cooling, the reaction solution is diluted with ethyl acetate, and thereto is added 10% aqueous potassium fluoride solution. The mixture is stirred at room temperature for one hour, and the reaction solution is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=30:1~10:1), and crystallized from methylene chloride/n-hexane to give 4-tert-butyl-N-[6-{2-(5-(2-thienyl)pyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]-benzenesulfonamide (209 mg) as crystals.

Workup

  1. temperatureis refluxed for 80 minutes
  2. temperatureAfter cooling
  3. washthe reaction solution is washed
  4. customdried
  5. customevaporated
  6. customto remove the solvent
  7. customThe residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=30:1~10:1)
  8. customcrystallized from methylene chloride/n-hexane

Sources & evidence

ORD record
ord-39c43a50322a4e8ebd23910cb724fcc3
Source dataset
uspto-grants-1998_03
Patent number
US05728706

Linked notes

Loading…