Triethylamine → Methyl 2-(4-hydroxy-2,6-dimethylphenyl)-[1,2,4]triazolo[1,5-a]pyridine-6-carboxylate

HRID 2272825Notes

Reaction equation

HRID 2272825 reaction equation
[NH2:1][N+:2]1[C:7]([NH2:8])=[CH:6][CH:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=1.CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[OH:26][C:27]1[CH:34]=[C:33]([CH3:35])[C:30]([CH:31]=O)=[C:29]([CH3:36])[CH:28]=1.C(N(CC)CC)C>CO>[CH3:12][O:11][C:9]([C:4]1[CH:5]=[CH:6][C:7]2[N:2]([N:1]=[C:31]([C:30]3[C:33]([CH3:35])=[CH:34][C:27]([OH:26])=[CH:28][C:29]=3[CH3:36])[N:8]=2)[CH:3]=1)=[O:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5910722,6-Dimethyl-4-hydroxybenzaldehydeHCID 38762462,4,6-Trimethylbenzene-1-sulfonateHCID 118129973Methyl 1,6-diaminopyridin-1-ium-3-carboxylate

Product 1

HCID 136992563Methyl 2-(4-hydroxy-2,6-dimethylphenyl)-[1,2,4]triazolo[1,5-a]pyridine-6-carboxylateYield 18%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of methyl 1,6-diaminopyridin-1-ium-3-carboxylate; 2,4,6-trimethylbenzenesulfonate (8 g, 21.68 mmol) in methanol (100 mL) is added 4-hydroxy-2,6-dimethyl-benzaldehyde (3.25 g, 21.68 mmol) and triethylamine (8.77 mL, 65.04 mmol) at 0° C. and the reaction mixture is stirred at room temperature for 48 hours. The reaction mixture is concentrated and extracted with EtOAc (100 mL). The combined organic extracts are washed with water (2×100 mL), saturated ammonium chloride solution (50 mL), brine solution (50 mL), and dried over anhydrous sodium sulphate, filtered, and evaporated to dryness. The crude material is purified by silica gel chromatography (combiflash 40 g redisep Rf column) and is eluted with 40-60% EtOAc in hexane to give the title compound as a pale yellow solid (1.2 g, 18%). LCMS m/z 298 [M+H]+.

Workup

  1. concentrationThe reaction mixture is concentrated
  2. extractionextracted with EtOAc (100 mL)
  3. washThe combined organic extracts are washed with water (2×100 mL), saturated ammonium chloride solution (50 mL), brine solution (50 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe crude material is purified by silica gel chromatography (combiflash 40 g redisep Rf column)
  8. washis eluted with 40-60% EtOAc in hexane

Sources & evidence

ORD record
ord-fc28606ae1bc4ba1be746ac9a757ac61
Source dataset
uspto-grants-2015_09
Patent number
US09120793B2

Reaction notes

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