Carbon Dioxide → 4-[1-[2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxo-acetyl]-4-piperidylidene]-4-phenyl-but-2-ynoic acid

HRID 606753Notes

Reaction equation

HRID 606753 reaction equation
[Li+].CC([N-]C(C)C)C.[C:9]1([C:15](=[C:18]2[CH2:23][CH2:22][N:21]([C:24](=[O:40])[C:25]([C:27]3[C:35]4[C:30](=[C:31]([O:38][CH3:39])[N:32]=[CH:33][C:34]=4[O:36][CH3:37])[NH:29][CH:28]=3)=[O:26])[CH2:20][CH2:19]2)[C:16]#[CH:17])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:41](=[O:43])=[O:42]>C1COCC1>[C:9]1([C:15](=[C:18]2[CH2:19][CH2:20][N:21]([C:24](=[O:40])[C:25]([C:27]3[C:35]4[C:30](=[C:31]([O:38][CH3:39])[N:32]=[CH:33][C:34]=4[O:36][CH3:37])[NH:29][CH:28]=3)=[O:26])[CH2:22][CH2:23]2)[C:16]#[C:17][C:41]([OH:43])=[O:42])[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 2724682Lithium diisopropylamideHCID 52799211-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-[4-(1-phenylprop-2-ynylidene)-1-piperidyl]ethane-1,2-dione

Product 1

HCID 52799274-[1-[2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxo-acetyl]-4-piperidylidene]-4-phenyl-but-2-ynoic acidYield 15%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of LDA [prepared from iPr2NH (0.15 mL, 1.070 mmol) and n-BuLi (0.52 mL, 0.936 mmol)] in THF (3 mL) at −78° C. under Ar was added 1-[4-(1-phenyl-1-ethynyl-methylene)-piperidin-1-yl]-2-(4,7-dimethoxy-6-azaindol-3-yl)-ethane-1,2-dione (0.160 g, 0.373 mmol). The solution was allowed to stir for 30 min and then a large excess of powdered dry ice was added directly into the flask. The mixture was allowed to warm to room temperature overnight and was then quenched with 10% aqueous HCl. The mixture was extracted with EtOAc (×3) and the combined organic layers were washed (H2O, brine), dried (Na2SO4) and concentrated. The residue was purified by preparative HPLC to afford the title compound as a colorless solid (0.026 g, 15%):

Workup

  1. customwas then quenched with 10% aqueous HCl
  2. extractionThe mixture was extracted with EtOAc (×3)
  3. washthe combined organic layers were washed (H2O, brine)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-a897a42731614efbb7026e0ed4407a4c
Source dataset
uspto-grants-2011_03
Patent number
US07915283B2

Reaction notes

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