Sodium hydride → HCID 53629192, compound

HRID 1924322Notes

Reaction equation

HRID 1924322 reaction equation
[CH2:1]([CH:4]1[CH2:8][NH:7][C:6](=[O:9])[CH2:5]1)[CH2:2][CH3:3].[H-].[Na+].[Br:12][C:13]1[C:14]([CH2:31]Cl)=[C:15]2[N:21]=[CH:20][N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C:16]2=[N:17][CH:18]=1>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:12][C:13]1[C:14]([CH2:31][N:7]2[CH2:8][CH:4]([CH2:1][CH2:2][CH3:3])[CH2:5][C:6]2=[O:9])=[C:15]2[N:21]=[CH:20][N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)[C:16]2=[N:17][CH:18]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 141781004-Propylpyrrolidin-2-oneHCID 57742993HCID 57742993, compound

Product 1

HCID 53629192HCID 53629192, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

4-propylpyrrolidin-2-one x1 (0.23 g, 1.1 eq, 1.8 mmol) is dissolved in absolute DMF (10 ml). Then 60% NaH (0.072 g, 1.1 eq, 1.8 mmol) is added at 0° C. in a flow of argon. The reaction mixture is stirred for 10 min at 0° C., and then for 10 min at room temperature to complete the reaction. The mixture is cooled again to 0° C. and a solution of 6-bromo-7-(chloromethyl)-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridine x212 (0.59 g, 1 eq) in absolute DMF (5 ml) additionally containing 0.1 g (0.2 eq, 0.32 mmol) of tetrabutylammonium bromide is added dropwise to the obtained suspension. The reaction mixture is stirred for 4 h at 5° C., then overnight at room temperature. The DMF is evaporated at 45° C. under 1 mmHg. The residue is partitioned in 10% aqueous NaH2PO4/ethyl acetate mixture. The aqueous layer is subjected to additional extraction with ethyl acetate. The combined extracts are dried with anhydrous sodium sulfate and evaporated. The residue is purified by chromatography on silicagel to afford 0.52 g of 1-{[6-bromo-3-(4-methoxybenzyl)-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one x213.

Workup

  1. waitfor 10 min at room temperature to complete
  2. customthe reaction
  3. temperatureThe mixture is cooled again to 0° C.
  4. additionis added dropwise to the obtained suspension
  5. stirringThe reaction mixture is stirred for 4 h at 5° C.
  6. customovernight
  7. customat room temperature
  8. customThe DMF is evaporated at 45° C. under 1 mmHg
  9. customThe residue is partitioned in 10% aqueous NaH2PO4/ethyl acetate mixture
  10. extractionThe aqueous layer is subjected to additional extraction with ethyl acetate
  11. dry with materialThe combined extracts are dried with anhydrous sodium sulfate
  12. customevaporated
  13. customThe residue is purified by chromatography on silicagel

Sources & evidence

ORD record
ord-f438fa6a90bf4c919a8de1328ba9714a
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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