Sodium Bicarbonate → HCID 23152898, compound

HRID 1012233Notes

Reaction equation

HRID 1012233 reaction equation
Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[F:21][C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=1.C(=O)([O-])O.[Na+]>COCCOC.O.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>[NH2:28][C:25]1[CH:26]=[CH:27][C:22]([F:21])=[CH:23][C:24]=1[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 11175076Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylateHCID 231525084-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 23152898HCID 23152898, compoundYield 95.7%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a suspension of methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (2.35 g, 6.98 mmol) obtained in the same manner as in the method described in WO03/010140 and 4-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamine (1.99 g, 8.38 mmol) in 1,2-dimethoxyethane (24 ml) and water (12 ml) were added sodium hydrogen carbonate (2.00 g, 24.0 mmol) and tetrakis(triphenylphosphine)palladium (400 mg, 0.34 mmol), and the mixture was heated under reflux for 14 hr. The mixture was allowed to cool to room temperature, and water was added to the reaction mixture. The mixture was extracted with ethyl acetate and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure and the residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1-3:1) to give methyl 2-(2-amino-5-fluorophenyl)-3-cyclohexyl-1H-indole-6-carboxylate (2.44 g, yield 95.7%).

Workup

  1. customobtained in the same manner as in the method
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for 14 hr
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1-3:1)

Sources & evidence

ORD record
ord-3a467a89ba5b4f23b5c8039558d93dc0
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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