3-Chloro-5-(trifluoromethyl)-2-pyridinamine → 8-Chloro-3-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester

HRID 1474176Notes

Reaction equation

HRID 1474176 reaction equation
[NH2:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[CH2:13]([O:15][C:16](=[O:22])[C:17](=O)[CH:18](Br)[CH3:19])[CH3:14]>O1CCOCC1>[CH2:13]([O:15][C:16]([C:17]1[N:1]=[C:2]2[C:7]([Cl:8])=[CH:6][C:5]([C:9]([F:12])([F:10])[F:11])=[CH:4][N:3]2[C:18]=1[CH3:19])=[O:22])[CH3:14]

Participants

4

Reactant 2

HCID 6072483-Chloro-5-(trifluoromethyl)-2-pyridinamineHCID 11117285Ethyl 3-bromo-2-oxobutanoate2×

Product 1

HCID 674949938-Chloro-3-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-amino-3-chloro-5-(trifluoromethyl)pyridine (11.3 g, 57.5 mmol) in dioxane (200 mL) at room temperature was added dropwise 3-bromo-2-oxo-butyric acid ethyl ester (12.017 g, 57.49 mmol, the product of Step A). The reaction mixture was heated to reflux for 24 h, cooled, and the dioxane was removed under reduced pressure. Chromatography on silica gel eluting with a hexane/ethyl acetate gradient afforded 17.3 g of 8-chloro-3-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester as a solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 24 h
  3. temperaturecooled
  4. customthe dioxane was removed under reduced pressure

Sources & evidence

ORD record
ord-f1661ee31b614707912dee49a15f4519
Source dataset
uspto-grants-2015_04
Patent number
US09018228B2

Reaction notes

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