Methyl iodide → 6-Chloro-2-(4-chlorophenyl)-3-((2,5-dimethyl-2H-1,2,3-triazol-4-yl)methyl)imidazo[1,2-a]pyridine

HRID 455142Notes

Reaction equation

HRID 455142 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:18][C:19]3[C:23]([CH3:24])=[N:22][NH:21][N:20]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.[C:25](=O)([O-])[O-].[K+].[K+].CI.C(I)C>CN(C=O)C.C1COCC1.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:18][C:19]3[C:23]([CH3:24])=[N:22][N:21]([CH3:25])[N:20]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=3)[N:10]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 6328Methyl iodideHCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 67028727HCID 67028727, compound

Product 1

HCID 670276816-Chloro-2-(4-chlorophenyl)-3-((2,5-dimethyl-2H-1,2,3-triazol-4-yl)methyl)imidazo[1,2-a]pyridineYield 26%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of the 6-chloro-2-(4-chlorophenyl)-3-((5-methyl-2H-1,2,3-triazol-4-yl)methyl)imidazo[1,2-a]pyridine (0.6-1.7 mmol, 1.0 eq) in DMF or THF (5-20 mL) was added potassium carbonate (3-5 eq) and either methyliodide or ethyliodide (3-5 eq) and the reaction mixture was heated at 75-85° C. for 18 h. After this time the reaction mixture was cooled and diluted with water (20-50 mL) and ethyl acetate (20-50 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (10-30 mL) and the combined organic layers were dried over Na2SO4, concentrated and the residue was purified by chromatography (silica gel, heptane/ethyl acetate gradient) or reverse phase preparatory HPLC (acetonitrile/water gradient) to obtain the desired product. (0.14 g, 26% yield). M/e+ 372.1 for C18H15Cl2N5 (M+H)+; 1H-NMR (500 MHz, CDCl3, δ) 8.09 (d, J=2.0 Hz, 1H), 7.69-7.67 (m, 2H), 7.58 (d, J=9.5 Hz, 1H), 7.45-7.44 (m, 2H), 7.17 (dd, J=9.5, 2.0 Hz, 1H), 4.33 (s, 2H), 4.05 (s, 3H), 2.01 (s, 3H).

Workup

  1. temperatureAfter this time the reaction mixture was cooled
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with ethyl acetate (10-30 mL)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by chromatography (silica gel, heptane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-6ae222208317495fa73df338850dbe3a
Source dataset
uspto-grants-2013_07
Patent number
US08497278B2

Reaction notes

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