3,4,5-Trimethoxyaniline → 2-(3,4,5-Trimethoxyanilino)-4-(3,6,6-trimethyl-4-oxo-5,7-dihydroindol-1-yl)benzamide

HRID 602393Notes

Reaction equation

HRID 602393 reaction equation
Br[C:2]1[CH:9]=[C:8]([N:10]2[C:18]3[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=3[C:12]([CH3:22])=[CH:11]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:23][O:24][C:25]1[CH:26]=[C:27]([CH:29]=[C:30]([O:34][CH3:35])[C:31]=1[O:32][CH3:33])[NH2:28].CC(C)([O-:39])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:35][O:34][C:30]1[CH:29]=[C:27]([NH:28][C:2]2[CH:9]=[C:8]([N:10]3[C:18]4[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=4[C:12]([CH3:22])=[CH:11]3)[CH:7]=[CH:6][C:3]=2[C:4]([NH2:5])=[O:39])[CH:26]=[C:25]([O:24][CH3:23])[C:31]=1[O:32][CH3:33]

Participants

7

Reactant 3

HCID 322853,4,5-TrimethoxyanilineHCID 118539082-Bromo-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indol-1-yl)-benzonitrileHCID 23676156Sodium t-butoxide

Product 1

HCID 118539122-(3,4,5-Trimethoxyanilino)-4-(3,6,6-trimethyl-4-oxo-5,7-dihydroindol-1-yl)benzamideYield 20%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

A “Personal Chemistry” microwave vial was charged with the title compound of Example 2 (107.1 mg, 0.3 mmol), 3,4,5-trimethoxyaniline (219.9 mg, 1.2 mmol), palladium (II) acetate (3.4 mg, 5 mol %), 1,1′-bis(diphenylphosphino)ferrocene (16.6 mg, 10 mol %), and sodium tert-butoxide (57.7 mg, 0.6 mmol). The reagents were suspended in toluene (2 mL) and were heated with microwave radiation to a temperature of 115° C. for fifteen minutes. After allowing the reaction vessel to cool, the suspension was filtered and the filtrate evaporated. The residue was purified by flash chromatography, and hydrolysis was performed by dissolving the product in 25% dimethylsulfoxide/ethanol, adding 5 drops of 1 N sodium hydroxide and 5 drops of 30% aqueous hydrogen peroxide, followed by stirring at room temperature for 3 hours. The DMSO/ethanol mixture was then diluted with water and extracted into EtOAc (3×). The combined organics were washed with brine (2×), dried over Na2SO4, and concentrated. The compound was purified by column chromatography (hexane/EtOAc) to yield 28.4 mg (20%) of the title compound as a yellow powder. LCMS m/z: (M+H) 478.3

Workup

  1. temperatureto cool
  2. filtrationthe suspension was filtered
  3. customthe filtrate evaporated
  4. customThe residue was purified by flash chromatography, and hydrolysis
  5. dissolutionby dissolving the product in 25% dimethylsulfoxide/ethanol
  6. additionadding 5 drops of 1 N sodium hydroxide and 5 drops of 30% aqueous hydrogen peroxide
  7. additionThe DMSO/ethanol mixture was then diluted with water
  8. extractionextracted into EtOAc (3×)
  9. washThe combined organics were washed with brine (2×)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customThe compound was purified by column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-8c7ab8e6a8364fe8997aa983f0e0da9b
Source dataset
uspto-grants-2011_03
Patent number
US07906529B2

Reaction notes

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