5-Amino-3-methyl-1-phenylpyrazole → 4-(3-methyl-1-phenyl-1H-pyrazol-5-ylamino)-N-(thiazol-2-yl)benzenesulfonamide

HRID 1644643Notes

Reaction equation

HRID 1644643 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.[NH2:59][C:60]1[N:64]([C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[N:63]=[C:62]([CH3:71])[CH:61]=1.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]>[CH3:71][C:62]1[CH:61]=[C:60]([NH:59][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)[N:64]([C:65]2[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=2)[N:63]=1

Participants

7

Reactant 4

HCID 708015-Amino-3-methyl-1-phenylpyrazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 10193184-Iodo-N-(thiazol-2-yl)benzenesulfonamideHCID 23676156Sodium t-butoxide

Product 1

HCID 252041734-(3-methyl-1-phenyl-1H-pyrazol-5-ylamino)-N-(thiazol-2-yl)benzenesulfonamideYield 48.6%

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 (21 mg, 0.036 mmol, 0.12 equiv) and 5-amino-3-methyl-1-phenylpyrazole (62 mg, 0.36 mmol, 1.2 equiv) in 4.0 mL of anhydrous 1,4-dioxane was added sodium tert-butoxide (100 mg, 0.90 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-3acad6ec622b45abb4d558ec6d61d871
Source dataset
uspto-grants-2012_02
Patent number
US08124610B2

Reaction notes

Loading…