Sodium hydride → 3-[(E)-4-phthalimido-2-butenyl]-3H-imidazo[4,5-b]pyridine

HRID 989632Notes

Reaction equation

HRID 989632 reaction equation
[H-].[Na+].[N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[N:11][C:6]=2[NH:5][CH:4]=1.Br[CH2:13]/[CH:14]=[CH:15]/[CH2:16][N:17]1[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]2[C:18]1=[O:27]>CN(C=O)C>[C:18]1(=[O:27])[N:17]([CH2:16]/[CH:15]=[CH:14]/[CH2:13][N:5]2[C:6]3=[N:11][CH:10]=[CH:9][CH:8]=[C:7]3[N:3]=[CH:4]2)[C:21](=[O:22])[C:20]2=[CH:23][CH:24]=[CH:25][CH:26]=[C:19]12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 105168412-(4-Bromobut-2-en-1-yl)isoindoline-1,3-dioneHCID 178420746HCID 178420746, compound

Product 1

HCID 185060273-[(E)-4-phthalimido-2-butenyl]-3H-imidazo[4,5-b]pyridineYield 32.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A slurry of NaH (1.02 g, 25.4 mmol) in DMF (50 mL) at room temperature was treated with 4-azabenzimidazole (2.90 g, 24.4 mmol). After 10 min., the reaction mixture was treated with a solution of (E)-N-(4-bromo-2-butenyl)phthalimide (5.7 g, 20.3 mmol) in DMF (5 mL) over 30 min. The reaction mixture was allowed to stir for 1 h, then quenched by careful addition of water (5 mL) and the reaction mixture was concentrated in vacuo. The resulting residue was diluted with CH2Cl2 (50 mL), washed with brine (2×25 mL), dried (MgSO4), and concentrated in vacuo to afford an off-white solid. Purification by flash chromatography (ethyl acetate containing 3% NH4OH) afforded 2.08 g of 3-[(E)-4-phthalimido-2-butenyl]-3H-imidazo[4,5-b]pyridine. Changing the chromatography solvent to 5% methanol/ethyl acetate containing 5% NH4OH afforded 1.66 g of 1-[(E)-4-phthalimido-2-butenyl]-1H-imidazo[4,5-b]pyridine; mass (CI) m/z=319 (M+H).

Workup

  1. customquenched by careful addition of water (5 mL)
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. additionThe resulting residue was diluted with CH2Cl2 (50 mL)
  4. washwashed with brine (2×25 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto afford an off-white solid
  8. customPurification by flash chromatography (ethyl acetate containing 3% NH4OH)

Sources & evidence

ORD record
ord-2c351c6ce32b4597b16c23445a1c0db3
Source dataset
uspto-grants-2002_10
Patent number
US06458771B1

Reaction notes

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