Methyl iodide → 2-Isopropyl-3-(1-methoxy-2-methylpropyl)pyrazolo[1,5-a]pyridine

HRID 483088Notes

Reaction equation

HRID 483088 reaction equation
[H-].[Na+].[CH:3]([C:6]1[C:14]([CH:15]([OH:19])[CH:16]([CH3:18])[CH3:17])=[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][N:8]2[N:7]=1)([CH3:5])[CH3:4].[CH3:20]I.[Cl-].[NH4+]>O1CCCC1>[CH:3]([C:6]1[C:14]([CH:15]([O:19][CH3:20])[CH:16]([CH3:18])[CH3:17])=[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][N:8]2[N:7]=1)([CH3:5])[CH3:4]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 133917031-(2-Isopropyl-pyrazolo[1,5-a]pyridin-3-yl)-2-methyl-propan-1-ol

Product 1

HCID 202425262-Isopropyl-3-(1-methoxy-2-methylpropyl)pyrazolo[1,5-a]pyridineYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 1.24 g of sodium hydride (55% oil suspension) in 20 ml of tetrahydrofuran was slowly added a solution of 3 g of 2-isopropyl-3-(1-hydroxy-2-methylpropyl)pyrazolo[1,5-a]pyridine in 5 ml of dry tetrahydrofuran under stirring and cooling. After the addition was completed, the stirring was continued for 5 minutes at room temperature, then reflux temperature for 15 minutes. The mixture was cooled with ice-water, to which 5.5 g of methyl iodide were added, and stirred for an hour at room temperature. After treating with aqueous 20% ammonium chloride solution, the mixture was extracted with ether. The ether layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated to dryness. The residue was applied to silica gel column chromatography, eluted with ethyl acetate-benzene (1:4) to give 2.8 g (88%) of the desired product as pale yellow oil.

Workup

  1. temperaturecooling
  2. additionAfter the addition
  3. temperaturereflux temperature for 15 minutes
  4. additionwere added
  5. stirringstirred for an hour at room temperature
  6. extractionthe mixture was extracted with ether
  7. washThe ether layer was washed with saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated to dryness
  10. washeluted with ethyl acetate-benzene (1:4)

Sources & evidence

ORD record
ord-6a97749c826a467c8a324751dd461b9d
Source dataset
uspto-grants-1986_03
Patent number
US04578392

Reaction notes

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