Trifluoroacetic acid → HCID 56601186, compound

HRID 1619601Notes

Reaction equation

HRID 1619601 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:46]=[C:47](B(O)O)[CH:48]=[CH:49][CH:50]=1.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:14])=[O:15])[CH:11]=[CH:12][C:7]=1[O:6][C:5]1[CH:35]=[CH:36][C:2]([C:49]2[CH:48]=[CH:47][CH:46]=[C:45]([O:44][CH3:43])[CH:50]=2)=[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 2734370(3-Methoxyphenyl)boronic acidHCID 58042316HCID 58042316, compound

Product 1

HCID 56601186HCID 56601186, compoundYield 61%

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), 3-methoxyphenylboronic acid (48 mg, 0.32 mmol), and potassium carbonate (62.5 mg, 0.452 mmol) in toluene (3 mL) was added tetrakistriphenylphosphinepalladium (0) (22.5 mg, 0.0195 mmol) and the mixture was sparged two times with argon. The reaction mixture was heated at reflux for 4.5 hours. After cooling to room temperature the reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated and washed with saturated sodium chloride solution, 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 yield 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 (49 mg, 61%) as a white solid.

Workup

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

Sources & evidence

ORD record
ord-1353348e283b4b0eb4c333ab7cb078f2
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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