Trifluoroacetic acid → HCID 56601187, compound

HRID 1619602Notes

Reaction equation

HRID 1619602 reaction equation
Br[C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13]([N:16](CC3C=CC(OC)=CC=3OC)[C:17]3[S:18][CH:19]=[CH:20][N:21]=3)(=[O:15])=[O:14])=[CH:9][C:8]=2[C:33]#[N:34])=[C:4]([C:37]2[N:38]([CH3:42])[N:39]=[CH:40][CH:41]=2)[CH:3]=1.[CH3:43][O:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)C(O)=O>C1(C)C=CC=CC=1.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:33]([C:8]1[CH:9]=[C:10]([S:13]([NH:16][C:17]2[S:18][CH:19]=[CH:20][N:21]=2)(=[O:15])=[O:14])[CH:11]=[CH:12][C:7]=1[O:6][C:5]1[CH:35]=[CH:36][C:2]([C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[O:44][CH3:43])=[CH:3][C:4]=1[C:37]1[N:38]([CH3:42])[N:39]=[CH:40][CH:41]=1)#[N:34]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 58042316HCID 58042316, compound

Product 1

HCID 56601187HCID 56601187, compoundYield 62.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[4-bromo-2-(2-methyl-2H-pyrazol-3-yl)-phenoxy]-3-cyano-N-(2,4-dimethoxy-benzyl)-N-thiazol-2-yl-benzenesulfonamide (Preparation 88, 98.5 mg, 0.148 mmol), 2-methoxyphenylboronic acid (48 mg, 0.32 mmol), and potassium carbonate (62.5 mg, 0.452 mmol) in toluene (3 mL) was added tetrakis(triphenylphosphine)palladium(0) (22.5 mg, 0.0195 mmol) and the mixture was sparged two times with argon. The reaction mixture was then heated at reflux for 4.5 hours and then allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate and washed with water and saturated sodium chloride solution. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by automated flash column chromatography using a 0-100% EtOAc/hexanes gradient to give a clear oil. This oil was dissolved in methylene chloride (5 mL) and treated with trifluoroacetic acid (1 mL, 10 mmol). After stirring for 1 hour, the reaction mixture was concentrated in vacuo and purified by automated flash column chromatography (0%-5% methanol in dichloromethane gradient elution) to yield the title compound (50 mg, 61%) as a white solid.

Workup

  1. customthe mixture was sparged two times with argon
  2. temperatureThe reaction mixture was then heated
  3. temperatureat reflux for 4.5 hours
  4. additionThe reaction mixture was diluted with ethyl acetate
  5. washwashed with water and saturated sodium chloride solution
  6. dry with materialThe organic layer was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by automated flash column chromatography
  10. customto give a clear oil
  11. concentrationthe reaction mixture was concentrated in vacuo
  12. custompurified by automated flash column chromatography (0%-5% methanol in dichloromethane gradient elution)

Sources & evidence

ORD record
ord-d267db70cb5f41fdb780954a703d5d17
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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