1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 4-(1-tert-butyl-3-(4-chlorobenzyl)-1H-pyrazol-5-ylamino)-N-(thiazol-2-yl)benzenesulfonamide

HRID 1644639Notes

Reaction equation

HRID 1644639 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[C:59]([N:63]1[C:67]([NH2:68])=[CH:66][C:65]([CH2:69][C:70]2[CH:75]=[CH:74][C:73]([Cl:76])=[CH:72][CH:71]=2)=[N:64]1)([CH3:62])([CH3:61])[CH3:60].CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:59]([N:63]1[C:67]([NH:68][C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]3[S:13][CH:14]=[CH:15][N:16]=3)(=[O:10])=[O:9])=[CH:4][CH:3]=2)=[CH:66][C:65]([CH2:69][C:70]2[CH:71]=[CH:72][C:73]([Cl:76])=[CH:74][CH:75]=2)=[N:64]1)([CH3:62])([CH3:60])[CH3:61]

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 10193184-Iodo-N-(thiazol-2-yl)benzenesulfonamideHCID 23676156Sodium t-butoxideHCID 575511731-Tert-butyl-3-(4-chlorobenzyl)-1H-pyrazol-5-amine

Product 1

HCID 252041014-(1-tert-butyl-3-(4-chlorobenzyl)-1H-pyrazol-5-ylamino)-N-(thiazol-2-yl)benzenesulfonamideYield 40%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of 4-iodo-N-thiazol-2-yl-benzenesulfonamide (100 mg, 0.3 mmol, 1.0 equiv), tris(dibenzylideneacetone)dipalladium(0) (10 mg, 0.01 mmol, 0.04 equiv), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (19 mg, 0.033 mmol, 0.12 equiv) and 2-tert-butyl-5-(4-chloro-benzyl)-2H-pyrazole-3-ylamine (86 mg, 0.33 mmol, 1.2 equiv) in 3.7 mL of anhydrous 1,4-dioxane was added sodium tert-butoxide (79 mg, 0.82 mmol, 3.0 equiv). The vial was capped, and the reaction mixture was heated 30 min at 150° C. in the microwave. The crude reaction mixture was filtered through celite then concentrated in vacuo. The residue was taken up in chloroform-methanol, concentrated onto celite, and purified via automated flash chromatography (12 g SiO2, gradient from hexanes to ethyl acetate). The appropriate fractions were collected, concentrated in vacuo, then lyophilized from water-acetonitrile to afford the product as an off-white solid (60 mg, 40%).

Workup

  1. customThe vial was capped
  2. customThe crude reaction mixture
  3. filtrationwas filtered through celite
  4. concentrationthen concentrated in vacuo
  5. concentrationconcentrated onto celite
  6. custompurified
  7. customThe appropriate fractions were collected
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d266c923de834f0784478cd24e82b61d
Source dataset
uspto-grants-2012_02
Patent number
US08124610B2

Reaction notes

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