3-Isoxazolamine, 5-(1,1-dimethylethyl)- → HCID 25204104, compound

HRID 1644642Notes

Reaction equation

HRID 1644642 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.[CH3:17][C:18]1(C)[C:31]2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2[C:19]1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[NH2:59][C:60]1[CH:64]=[C:63](C(C)(C)C)[O:62][N: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]>[C:18]([C:60]1([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)[CH:64]=[CH:63][O:62][NH:61]1)([CH3:31])([CH3:19])[CH3:17]

Participants

7

Reactant 4

HCID 1714733-Isoxazolamine, 5-(1,1-dimethylethyl)-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-butoxide

Product 1

HCID 25204104HCID 25204104, compoundYield 1,478.4%

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 (50 mg, 0.1 mmol, 1.0 equiv), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 0.005 mmol, 0.04 equiv), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (10 mg, 0.0016 mmol, 0.12 equiv) and 3-amino-5-tert-butylisoxazole (23 mg, 0.16 mmol, 1.2 equiv) in 1.8 mL of anhydrous 1,4-dioxane was added sodium tert-butoxide (39 mg, 0.41 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 purified further via reverse phase HPLC. The solvent was removed by lyophilization to afford the product as a white solid (9 mg, 20%).

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
  9. custompurified further via reverse phase HPLC
  10. customThe solvent was removed by lyophilization

Sources & evidence

ORD record
ord-12fcc208f79847769d4dd254cbc1958c
Source dataset
uspto-grants-2012_02
Patent number
US08124610B2

Reaction notes

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