Benzonitrile → Methyl 8-methyl-2-phenyl-[1,2,4]triazolo[1,5-A]pyridine-7-carboxylate

HRID 1802154Notes

Reaction equation

HRID 1802154 reaction equation
CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:14][N+:15]1[CH:20]=[CH:19][C:18]([C:21]([O:23][CH3:24])=[O:22])=[C:17]([CH3:25])[CH:16]=1.[C:26](#[N:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH-].[K+]>C(O)C.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:25][C:17]1[C:16]2[N:15]([N:14]=[C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:33]=2)[CH:20]=[CH:19][C:18]=1[C:21]([O:23][CH3:24])=[O:22]

Participants

6

Reactant 3

HCID 7505BenzonitrileHCID 14797Potassium HydroxideHCID 866660171-Amino-4-(methoxycarbonyl)-3-methylpyridinium 2,4,6-trimethylbenzenesulfonate

Product 1

HCID 67774641Methyl 8-methyl-2-phenyl-[1,2,4]triazolo[1,5-A]pyridine-7-carboxylateYield 36.1%

Reagents, catalysts & solvents 2

HCID 165397Cupric acetate monohydrateCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a suspension of 1-amino-4-(methoxycarbonyl)-3-methylpyridinium2,4,6-trimethylbenzenesulfonate (2.409 g, 6.57 mmol) in ethanol (40 ml) are added benzonitrile (675 μl, 6.57 mmol), copper(II) acetate monohydrate (1.31 g, 6.57 mmol) and finally potassium hydroxide (2M in ethanol, 3.62 ml, 7.23 mmol). The resulting mixture is heated to 90° C. and stirred for 18 hours under air atmosphere while air was slightly bubbled through the reaction mixture. The dark green mixture is poured on sat. aqueous sodium bicarbonate solution (100 ml) and stirred for 5 minutes, then extracted twice with ethyl acetate (filtration over dicalite is required because of emulsion). The combined organic layers are washed twice with water and brine, dried with magnesium sulfate and the solvent is evaporated. The crude material is loaded on silica and separated by flash chromatography on a 70 g silica column using heptane/ethyl acetate 10-30% as eluent affording methyl 8-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (634 mg, 36%) as a white solid (MS: m/z=268.1 (M+H+) and methyl 6-methyl-2-phenyl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate (112 mg, 6.37%) as a white solid. MS: m/z=268.1 (M+H+).

Workup

  1. customwas slightly bubbled through the reaction mixture
  2. additionThe dark green mixture is poured on sat. aqueous sodium bicarbonate solution (100 ml)
  3. stirringstirred for 5 minutes
  4. extractionextracted twice with ethyl acetate (filtration over dicalite is required because of emulsion)
  5. washThe combined organic layers are washed twice with water and brine
  6. dry with materialdried with magnesium sulfate
  7. customthe solvent is evaporated
  8. customseparated by flash chromatography on a 70 g silica column

Sources & evidence

ORD record
ord-fadcc925c721422285392ab91d85088a
Source dataset
uspto-grants-2013_01
Patent number
US08349824B2

Reaction notes

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