Trimethylsilylacetylene → 1-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-[4-(1-phenyl-3-trimethylsilyl-prop-2-ynylidene)-1-piperidyl]ethane-1,2-dione

HRID 1394433Notes

Reaction equation

HRID 1394433 reaction equation
Br[C:2](=[C:9]1[CH2:14][CH2:13][N:12]([C:15](=[O:31])[C:16]([C:18]2[C:26]3[C:21](=[C:22]([O:29][CH3:30])[N:23]=[CH:24][C:25]=3[O:27][CH3:28])[NH:20][CH:19]=2)=[O:17])[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:32][Si:33]([C:36]#[CH:37])([CH3:35])[CH3:34]>N1CCCCC1.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.[Cu]I>[C:3]1([C:2](=[C:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:31])[C:16]([C:18]3[C:26]4[C:21](=[C:22]([O:29][CH3:30])[N:23]=[CH:24][C:25]=4[O:27][CH3:28])[NH:20][CH:19]=3)=[O:17])[CH2:11][CH2:10]2)[C:37]#[C:36][Si:33]([CH3:35])([CH3:34])[CH3:32])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 5279817Piperidine, 4-(bromophenylmethylene)-1-[2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-1,2-dioxoethyl]-

Product 1

HCID 52799201-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-[4-(1-phenyl-3-trimethylsilyl-prop-2-ynylidene)-1-piperidyl]ethane-1,2-dioneYield 39%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 8082PiperidineSolvent

Conditions

Temperature
60 °C

Procedure

As shown in Scheme 31 to a solution of 1-[4-(1-bromo-1-phenyl-methylene)-piperidin-1-yl]-2-(4,7-dimethoxy-6-azaindol-3-yl)-ethane-1,2-dione (0.094 g, 0.195 mmol), PdCl2(PhCN)2 (0.005 g, 0.0117 mmol), and CuI (0.005 g, 0.0252 mmol) in piperidine (1.5 mL) was added trimethylsilylacetylene (0.070 mL, 0.495 mmol). The mixture was heated at 60° C. for 2 h and the solvent removed in vacuo. The residue was diluted with EtOAc and H2O, the organic phase was separated and the aqueous phase was re-extracted with EtOAc (×2). The combined organic layers were washed, (H2O, brine), dried (Na2SO4) and evaporated, and the residue was purified by preparative HPLC to give the title compound as a colorless solid (0.038 g, 39%).

Workup

  1. customthe solvent removed in vacuo
  2. additionThe residue was diluted with EtOAc and H2O
  3. customthe organic phase was separated
  4. extractionthe aqueous phase was re-extracted with EtOAc (×2)
  5. washThe combined organic layers were washed, (H2O, brine),
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-99a8b822239f4f92af7679ec56b5f586
Source dataset
uspto-grants-2008_03
Patent number
US07348337B2

Reaction notes

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