Sodium Carbonate → methyl 2-[3-(acetylamino)-2-aminophenyl]-3-cyclohexyl-1H-indole-6-carboxylate

HRID 1518229Notes

Reaction equation

HRID 1518229 reaction equation
[C:1]([NH:4][C:5]1[C:6]([NH2:14])=[C:7](B(O)O)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].Br[C:16]1[NH:17][C:18]2[C:23]([C:24]=1[CH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)=[CH:22][CH:21]=[C:20]([C:31]([O-:33])=[O:32])[CH:19]=2.N1C2C(=CC=C(C(OC)=O)C=2)C=[CH:35]1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([NH:4][C:5]1[C:6]([NH2:14])=[C:7]([C:16]2[NH:17][C:18]3[C:23]([C:24]=2[CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:22][CH:21]=[C:20]([C:31]([O:33][CH3:35])=[O:32])[CH:19]=3)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 639844Methyl indole-6-carboxylateHCID 53692531[3-(Acetylamino)-2-aminophenyl]boronic acidHCID 863099302-bromo-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 68708755methyl 2-[3-(acetylamino)-2-aminophenyl]-3-cyclohexyl-1H-indole-6-carboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

[3-(acetylamino)-2-aminophenyl]boronic acid (prepared as described in Example 5, Step 1 above) (1.1 eq) was added to a solution of 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared from commercially available methyl indole-6-carboxylate as described in WO 2004/087714) in dioxane (0.06 M). 2M aqueous Na2CO3 (4 eq) was introduced and the mixture degassed by sonication under a N2 atmosphere prior to introducing bis(triphenylphosphine)palladium(II) dichloride (0.2 eq) and heating at 105° C. for 2 h. The reaction was allowed to cool to RT before partitioning between EtOAc and water. The aqueous phase was extracted a second time with EtOAc and the combined organics washed with water, brine before being dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by flash chromatography (5% MeOH/CH2Cl2) afforded the title compound as a glass (59%). MS (ES+) m/z 406 (M+H)+.

Workup

  1. customthe mixture degassed by sonication under a N2 atmosphere
  2. temperatureto cool to RT
  3. custombefore partitioning between EtOAc and water
  4. extractionThe aqueous phase was extracted a second time with EtOAc
  5. washthe combined organics washed with water, brine
  6. dry with materialbefore being dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e6d1dbf9dbfb4baa9fc1559daab62ff8
Source dataset
uspto-grants-2012_07
Patent number
US08232390B2

Reaction notes

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