2-(Tri-n-butylstannyl)thiophene → 4-(tert-butyl)-N-[1-methyl-4-(4-methylphenyl)-3-(2-{[5-(2-thienyl)-2-pyrimidinyl]oxy}ethoxy)-1H-pyrazol-5-yl]benzenesulfonamide

HRID 1062718Notes

Reaction equation

HRID 1062718 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][CH2:9][CH2:10][O:11][C:12]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)=[C:15]([NH:24][S:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([CH3:37])([CH3:36])[CH3:35])=[CH:30][CH:29]=3)(=[O:27])=[O:26])[N:14]([CH3:38])[N:13]=2)=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:44]1[S:45][CH:46]=[CH:47][CH:48]=1)CCC>O1CCOCC1.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:34]([C:31]1[CH:32]=[CH:33][C:28]([S:25]([NH:24][C:15]2[N:14]([CH3:38])[N:13]=[C:12]([O:11][CH2:10][CH2:9][O:8][C:5]3[N:4]=[CH:3][C:2]([C:44]4[S:45][CH:46]=[CH:47][CH:48]=4)=[CH:7][N:6]=3)[C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:27])=[O:26])=[CH:29][CH:30]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

6

Reactant 2

HCID 27793732-(Tri-n-butylstannyl)thiopheneHCID 9894949N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-4-(tert-butyl)benzenesulfonamide

Product 1

HCID 222819974-(tert-butyl)-N-[1-methyl-4-(4-methylphenyl)-3-(2-{[5-(2-thienyl)-2-pyrimidinyl]oxy}ethoxy)-1H-pyrazol-5-yl]benzenesulfonamideYield 67.2%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-4-(tert-butyl)benzenesulfonamide (Example 3) (111 mg) in 1,4-dioxane (5 ml) at room temperature was added 2-(tributylstannyl)thiophene (103 mg) and bis(triphenylphosphine)palladium (II) chloride (6.5 mg) the mixture was stirred and heated to reflux for 3 hrs followed by 16 hrs. at room temperature. To the mixture was added bis(triphenylphosphine) palladium (II) chloride (6.5 mg) and the mixture was heated to reflux for a further 4 hrs. The reaction was diluted with ethyl acetate (100 ml), washed with a 10% solution of potassium fluoride in water (100 ml) and brine (100 ml), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica (10 g) eluted with ethyl acetate:hexane (1:1) to yield the title compound as a white solid (75 mg).

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 hrs
  3. customat room temperature
  4. temperaturethe mixture was heated
  5. temperatureto reflux for a further 4 hrs
  6. washwashed with a 10% solution of potassium fluoride in water (100 ml) and brine (100 ml)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by column chromatography on silica (10 g)
  11. washeluted with ethyl acetate:hexane (1:1)

Sources & evidence

ORD record
ord-b0cd2bce561e4f03b291b6351d2e247b
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

Loading…