1-Methyl-1H-1,2,3-triazole → (2,6-Dimethyl-4-pyridinyl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone

HRID 926494Notes

Reaction equation

HRID 926494 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[N:8]1.CON(C)[C:15](=[O:24])[C:16]1[CH:21]=[C:20]([CH3:22])[N:19]=[C:18]([CH3:23])[CH:17]=1>C1COCC1>[CH3:23][C:18]1[CH:17]=[C:16]([C:15]([C:11]2[N:7]([CH3:6])[N:8]=[N:9][CH:10]=2)=[O:24])[CH:21]=[C:20]([CH3:22])[N:19]=1

Participants

5

Reactant 3

HCID 1401191-Methyl-1H-1,2,3-triazoleHCID 18736278N-Methoxy-N,2,6-trimethylisonicotinamideHCID 178418339Butyllithium

Product 1

HCID 107502509(2,6-Dimethyl-4-pyridinyl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of n-BuLi (3.8 mL, 9.5 mmol, 2.5 M solution in hexane) was added slowly to a solution of 1-methyl-1H-1,2,3-triazole (0.83 g, 10 mmol) in THF (48 mL) at −50° C. After addition, stirring was continued for an additional 30 minutes and N-methoxy-N,2,6-trimethylisonicotinamide (0.97 g, 5.0 mmol, Intermediate 29: step a) dissolved in THF (12 mL) was slowly added. An additional 2 mL of THF was used to complete the quantitative addition. The mixture was stirred at −50° C. for 5 minutes then warmed to room temperature and stirred overnight. The solution was quenched with saturated aqueous NH4Cl. H2O was added and layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts washed with brine, dried over MgSO4, filtered and evaporated in vacuo. The crude product was purified using flash column chromatography (0 to 100% EtOAc/DCM) to provide the title compound.

Workup

  1. additionAfter addition
  2. additionwas slowly added
  3. additionthe quantitative addition
  4. stirringThe mixture was stirred at −50° C. for 5 minutes
  5. stirringstirred overnight
  6. customThe solution was quenched with saturated aqueous NH4Cl
  7. additionH2O was added
  8. customlayers were separated
  9. extractionThe aqueous layer was extracted with EtOAc
  10. washthe combined organic extracts washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. customThe crude product was purified

Sources & evidence

ORD record
ord-29d853f380bd48a8b16114eeff8270bc
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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