Triphenylphosphine → 4-tert-Butyl-N-{5-(2-benzothienyl)-6-[2-(5-methylthiopyrimidin-2-yloxy)-ethoxy]pyrimidin-4-yl}benzenesulfonamide

HRID 1599023Notes

Reaction equation

HRID 1599023 reaction equation
Br[C:2]1[C:3]([NH:20][S:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:26][CH:25]=2)(=[O:23])=[O:22])=[N:4][CH:5]=[N:6][C:7]=1[O:8][CH2:9][CH2:10][O:11][C:12]1[N:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][N:13]=1.[S:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[CH:36]=[C:35]1[Sn](CCCC)(CCCC)CCCC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(C1(C)C(O)=C(C(C)(C)C)C=CC1)(C)(C)C.[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.[Cu]Br.O1CCOCC1>[C:30]([C:27]1[CH:28]=[CH:29][C:24]([S:21]([NH:20][C:3]2[C:2]([C:35]3[S:34][C:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=4[CH:36]=3)=[C:7]([O:8][CH2:9][CH2:10][O:11][C:12]3[N:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][N:13]=3)[N:6]=[CH:5][N:4]=2)(=[O:23])=[O:22])=[CH:25][CH:26]=1)([CH3:33])([CH3:32])[CH3:31]

Participants

10

Reactant 5

HCID 11776TriphenylphosphineHCID 522689Potassium FluorideHCID 2735461(1-Benzothiophen-2-yl)tributylstannaneHCID 11071742N-{5-bromo-6-[2-(5-methylthiopyrimidin-2-yloxy)ethoxy]pyrimidin-4-yl}-4-tert-butylbenzenesulfonamideHCID 666371922,6-Di-t-butylcresol

Product 1

HCID 98736364-tert-Butyl-N-{5-(2-benzothienyl)-6-[2-(5-methylthiopyrimidin-2-yloxy)-ethoxy]pyrimidin-4-yl}benzenesulfonamideYield 83%

Reagents, catalysts & solvents 4

HCID 24593copper(I) bromideCatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of N-{5-bromo-6-[2-(5-methylthiopyrimidin-2-yloxy)ethoxy]-pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide (200 mg), 2-benzothienyl tributyltin (460 mg), bis(triphenylphosphine)palladium (II) chloride (51 mg), triphenylphosphine (28 mg), copper (I) bromide (21 mg), a few crystals of 2,6-di-tert-butylcresol and dioxane (6 ml) is refluxed for two hours. After cooling, the reaction solution is diluted with ethyl acetate and an aqueous potassium fluoride solution, and the mixture is stirred at room temperature for 60 minutes. The insoluble materials are removed by filtration, and the filtrate is extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated under reduced pressure to remove the solvent. The residue is purified by silica gel column chromatography (solvent; methylene chloride:acetone=30:1), and recrystallized from ethyl acetate to give the title compound (182 mg).

Workup

  1. temperatureAfter cooling
  2. customThe insoluble materials are removed by filtration
  3. extractionthe filtrate is extracted with ethyl acetate
  4. washThe ethyl acetate layer is washed
  5. customdried
  6. customevaporated under reduced pressure
  7. customto remove the solvent
  8. customThe residue is purified by silica gel column chromatography (solvent; methylene chloride:acetone=30:1)
  9. customrecrystallized from ethyl acetate

Sources & evidence

ORD record
ord-22457c575d084090958bf23f41e06192
Source dataset
uspto-grants-1998_04
Patent number
US05739333

Reaction notes

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