Tert-butyl 8-chloro-3-phenyl[1,2,4]triazolo[4,3-a]pyridine-6-carboxylate → Tert-butyl 8-(5-methylpyridin-2-yl)-3-phenyl[1,2,4]triazolo[4,3-a]pyridine-6-carboxylate

HRID 592299Notes

Reaction equation

HRID 592299 reaction equation
Cl[C:2]1[C:3]2[N:4]([C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:16][N:17]=2)[CH:5]=[C:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:7]=1.[Br-].[CH3:25][C:26]1[CH:27]=[CH:28][C:29]([Zn+])=[N:30][CH:31]=1>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:25][C:26]1[CH:27]=[CH:28][C:29]([C:2]2[C:3]3[N:4]([C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[N:16][N:17]=3)[CH:5]=[C:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:7]=2)=[N:30][CH:31]=1

Participants

5

Reactant 2

HCID 66690717Tert-butyl 8-chloro-3-phenyl[1,2,4]triazolo[4,3-a]pyridine-6-carboxylateHCID 178427808HCID 178427808, compound

Product 1

HCID 66690581Tert-butyl 8-(5-methylpyridin-2-yl)-3-phenyl[1,2,4]triazolo[4,3-a]pyridine-6-carboxylateYield 26.6%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a degassed solution of tert-butyl 8-chloro-3-phenyl[1,2,4]triazolo[4,3-a]pyridine-6-carboxylate (0.22 g, 0.67 mmol) and bis(tri-tert-butylphosphine)palladium(0) (17.1 mg, 33 μmol) in dioxane (2 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 4.0 mL, 2.0 mmol). The mixture was heated 75° C. After 181, the mixture was cooled to ambient temperature and concentrated. Saturated aqueous sodium bicarbonate was added and the mixture was extracted with dichloromethane (3×). The combined organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→75% hexanes/ethyl acetate) gave the title compound (69 mg): LC-MS [M+1]=387.1.

Workup

  1. temperatureAfter 181, the mixture was cooled to ambient temperature
  2. concentrationconcentrated
  3. additionSaturated aqueous sodium bicarbonate was added
  4. extractionthe mixture was extracted with dichloromethane (3×)
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (100% hexanes→75% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-02140b9b11094579bdb6822f5b63f29d
Source dataset
uspto-grants-2016_01
Patent number
US09238647B2

Reaction notes

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