Sodium Carbonate → HCID 68706296, compound

HRID 1518234Notes

Reaction equation

HRID 1518234 reaction equation
Br[C:2]1[N:3]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[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.[NH:27]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33](C(OC)=O)[CH:34]=2)[CH:29]=[CH:28]1.C([O-])([O-])=O.[Na+].[Na+].N1C2C(=C(B(O)O)C=CC=2)C=C1>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>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([O:19][CH3:20])=[O:18])=[CH:7][CH:8]=3)[N:3]([CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23])[C:2]=2[C:31]2[C:30]3[CH:29]=[CH:28][NH:27][C:35]=3[CH:34]=[CH:33][CH:32]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 639844Methyl indole-6-carboxylateHCID 27631731H-Indole-4-boronic acidHCID 21105286HCID 21105286, compound

Product 1

HCID 68706296HCID 68706296, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of methyl 2-bromo-3-cyclohexyl-1-[2-(dimethylamino)-2-oxoethyl]-1H-indole-6-carboxylate (prepared from commercially available methyl indole-6-carboxylate as described in WO 2004/087714) in dioxane (0.15 M) were added 6 eq of Na2CO3 (2 M aqueous solution), 1.5 eq of 1H-indol-4-ylboronic acid and 0.2 eq of bis(triphenylphosphine)palladium(II) dichloride. The mixture was heated at reflux for 1.5 h. The reaction mixture was filtered and then the filtrate was diluted with EtOAc. The organic phase was washed with aqueous Na2CO3, brine and dried over Na2SO4 before being filtered and concentrated in vacuo. The crude was purified by flash chromatography (Biotage cartridge, 6.0:4.0 EtOAc/PE) to afford the title compound (95%). MS (ES+) m/z 458 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1.5 h
  3. filtrationThe reaction mixture was filtered
  4. additionthe filtrate was diluted with EtOAc
  5. washThe organic phase was washed with aqueous Na2CO3, brine
  6. dry with materialdried over Na2SO4
  7. filtrationbefore being filtered
  8. concentrationconcentrated in vacuo
  9. customThe crude was purified by flash chromatography (Biotage cartridge, 6.0:4.0 EtOAc/PE)

Sources & evidence

ORD record
ord-23f5bba75e014bc0a159ad89238e7cf0
Source dataset
uspto-grants-2012_07
Patent number
US08232390B2

Reaction notes

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