Hydrochloric Acid → 3-cyclohexyl-N-(N,N-dimethylsulfamoyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxamide

HRID 494067Notes

Reaction equation

HRID 494067 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]([NH:19][S:20]([N:23]([CH3:25])[CH3:24])(=[O:22])=[O:21])=[O:18])[CH:5]=2.B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2[C:42]2[C:47]([O:48][CH3:49])=[CH:46][CH:45]=[CH:44][C:43]=2OC)CCCCC1.[C:58](=O)([O-])[O-:59].[K+].[K+].Cl>C1(C)C=CC=CC=1.C(OCC)(=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([NH:19][S:20](=[O:22])(=[O:21])[N:23]([CH3:25])[CH3:24])=[O:18])=[CH:7][CH:8]=3)[NH:3][C:2]=2[C:44]2[CH:45]=[CH:46][C:47]([O:48][CH3:49])=[CH:42][C:43]=2[CH:58]=[O:59])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 61668Boronic AcidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 587651502-bromo-3-cyclohexyl-N-(dimethylsulfamoyl)-1H-indole-6-carboxamide

Product 1

HCID 597500763-cyclohexyl-N-(N,N-dimethylsulfamoyl)-2-(2-formyl-4-methoxyphenyl)-1H-indole-6-carboxamide

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of the 2-Bromo-3-cyclohexyl-N-[(dimethylamino)sulfonyl]-1H-indole-6-carboxamide (4.28 g, 0.01 mol), boronic acid (2.7 g, 0.015 mol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-biphenyl (41 mg, 0.0001 mol), palladium acetate (11.2 mg), and finely ground potassium carbonate (4.24 g, 0.02 mol) in toluene (30 mL) was stirred under reflux and under nitrogen for 30 min, at which time LC/MS analysis showed the reaction to be complete. The reaction mixture was then diluted with ethyl acetate and water, and then acidified with an excess of dilute HCl. The ethyl acetate layer was then collected and washed with dilute HCl, water and brine. The organic solution was then dried (magnesium sulfate), filtered and concentrated to give a gum. The gum was diluted with hexanes (250 ml) and ethyl acetate (25 mL), and the mixture was stirred for 20 hr at 22° C. during which time the product was transformed into a bright yellow granular solid (4.8 g) which was used directly without further purification.

Workup

  1. temperatureunder reflux and under nitrogen for 30 min, at which time LC/MS analysis
  2. customthe reaction
  3. customThe ethyl acetate layer was then collected
  4. washwashed with dilute HCl, water and brine
  5. dry with materialThe organic solution was then dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a gum
  9. stirringthe mixture was stirred for 20 hr at 22° C. during which time the product
  10. customwas used directly without further purification

Sources & evidence

ORD record
ord-a1db0a003b2544b4808b01a6f4046d9d
Source dataset
uspto-grants-2009_05
Patent number
US07538102B2

Reaction notes

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