Sodium Carbonate → 1-(3-Fluoro5-(4-methyl-3-pyridyl)phenylcarbamoyl)-5-methoxy-6-trifluoromethylindoline

HRID 989199Notes

Reaction equation

HRID 989199 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:25][CH3:26])=[C:18]([C:21]([F:24])([F:23])[F:22])[CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[C:6](I)[CH:7]=1.[CH3:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][C:29]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([N:12]2[C:20]3[C:15](=[CH:16][C:17]([O:25][CH3:26])=[C:18]([C:21]([F:24])([F:23])[F:22])[CH:19]=3)[CH2:14][CH2:13]2)=[O:11])[CH:5]=[C:6]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][C:28]=2[CH3:27])[CH:7]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27627114-Methylpyridine-3-Boronic AcidHCID 180051431-(3-Fluoro-5-iodophenylcarbamoyl)-5-methoxy-6-trifluoromethylindoline

Product 1

HCID 180051521-(3-Fluoro5-(4-methyl-3-pyridyl)phenylcarbamoyl)-5-methoxy-6-trifluoromethylindoline

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 1-(3-fluoro-5-iodophenylcarbamoyl)-5-methoxy-6-trifluoromethylindoline (D17, 0.31 g, 0.65 mmol), 4-methyl-3-pyridylboronic acid (88 mg, 0.65 mmol), tetrakis (triphenylphosphine) palladium (0) (23 mg, 0.02 mmol) and sodium carbonate (0.31 g, 3.0 mmol) in 1,2-dimethoxyethane (20 mL) and water (2 mL) was heated under reflux for 24 h, then cooled and poured into water. The aqueous mixture was extracted with dichloromethane/methanol, and the organic extract was washed with brine, dried and evaporated. The residue was chromatographed on silica gel eluted with 2-3% methanol/dichloromethane to give the title compound, which was recrystallised from dichloromethane/petrol (80 mg, 28%), m.p. 191-5° C.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 24 h
  3. temperaturecooled
  4. extractionThe aqueous mixture was extracted with dichloromethane/methanol
  5. extractionthe organic extract
  6. washwas washed with brine
  7. customdried
  8. customevaporated
  9. customThe residue was chromatographed on silica gel
  10. washeluted with 2-3% methanol/dichloromethane

Sources & evidence

ORD record
ord-173da943f4af4dc5b860054466aad257
Source dataset
uspto-grants-2003_10
Patent number
US06638953B2

Reaction notes

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