Potassium Carbonate → 5,7-dichloro-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-3H-imidazo[4,5-b]pyridine

HRID 1399775Notes

Reaction equation

HRID 1399775 reaction equation
C(=O)([O-])[O-].[K+].[K+].[Cl:7][C:8]1[N:13]=[C:12]2[N:14]=[CH:15][NH:16][C:11]2=[C:10]([Cl:17])[CH:9]=1.Br[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[C:21]=1[CH3:30]>CN(C)C=O>[Cl:7][C:8]1[N:13]=[C:12]2[N:14]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:27])([F:28])[F:29])[C:21]=3[CH3:30])[CH:15]=[N:16][C:11]2=[C:10]([Cl:17])[CH:9]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27756171-(Bromomethyl)-2-methyl-3-(trifluoromethyl)benzeneHCID 59498025,7-dichloro-1H-imidazo[4,5-b]pyridine

Product 1

HCID 896477785,7-dichloro-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-3H-imidazo[4,5-b]pyridineYield 47.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Potassium carbonate (1139 mg, 8.24 mmol) was added to a solution of 5,7-dichloro-1H-imidazo[4,5-b]pyridine (500 mg, 2.66 mmol) in N,N-Dimethylformamide (DMF) (8.5 mL) and the mixture was stirred for 25 min. 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (942 mg, 3.72 mmol) was then added and the reaction mixture was stirred at rt overnight. The mixture was partitioned between water and EtOAc. The aqueous layer was extracted with additional EtOAc (2×25 mL). The combined organic extracts were washed with brine, dried over Na2SO4 and evaporated. The residue was purified on silica gel (15 to 30% EtOAc in hexanes) to give 5,7-dichloro-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-3H-imidazo[4,5-b]pyridine (456 mg, 1.266 mmol, 47.6% yield) as an off-white powder. MS (ES+) m/e 359 (MH+) 1H NMR (400 MHz, DMSO-d6) δ ppm 8.64 (s, 1H), 7.68 (s, 1H), 7.66 (d, J=8.08 Hz, 1H), 7.33 (t, J=7.71 Hz, 1H), 7.07 (d, J=7.83 Hz, 1H), 5.62 (s, 2H) (Ar—CH3 hidden under DMSO peak).

Workup

  1. stirringthe reaction mixture was stirred at rt overnight
  2. customThe mixture was partitioned between water and EtOAc
  3. extractionThe aqueous layer was extracted with additional EtOAc (2×25 mL)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe residue was purified on silica gel (15 to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-475bdf12c56846fda3d7af4d64f0c520
Source dataset
uspto-grants-2014_12
Patent number
US08906910B2

Reaction notes

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