Potassium Carbonate → 2-dimethylamino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 2246436Notes

Reaction equation

HRID 2246436 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[C:11]([N:13]([CH3:15])[CH3:14])[NH:12][C:4]=2[CH:3]=1.[CH2:16]([O:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][C:20]=1[C:28]([F:31])([F:30])[F:29])[CH3:17].C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[CH3:14][N:13]([CH3:15])[C:11]1[NH:12][C:4]2[CH:3]=[C:2]([C:22]3[CH:23]=[CH:24][C:19]([O:18][CH2:16][CH3:17])=[C:20]([C:28]([F:29])([F:31])[F:30])[CH:21]=3)[N:7]=[C:6]([C:8]#[N:9])[C:5]=2[N:10]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 445581844-Ethoxy-3-(trifluoromethyl)benzeneboronic acidHCID 589381326-chloro-2-dimethylamino-1H-imidazo[4,5-c]pyridine-4-carbonitrile

Product 1

HCID 589381232-dimethylamino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrileYield 3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 6-chloro-2-dimethylamino-1H-imidazo[4,5-c]pyridine-4-carbonitrile (100 mg, 0.45 mmol), 4-ethoxy-3-trifluoromethyl-phenyl boronic acid (198 mg, 0.88 mmol) tetrakis(triphenylphosphine)palladium(0) (50 mg, ˜10 mol %) and potassium carbonate (193.0 mg, 1.39 mmol) in THF (3 ml) was heated to 130° C. for 6 minutes in the “Smith” microwave. The crude mixture was concentrated under reduced pressure to remove THF before partitioning between ethyl acetate and water. The organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure. The material was then dissolved in DMSO and purified in aliquots by preparative HPLC. The desired fractions were collected and concentrated to give a white solid which was washed with ether to afford 2-dimethylamino-6-(4-ethoxy-3-trifluoromethyl-phenyl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (5.0 mg)

Workup

  1. concentrationThe crude mixture was concentrated under reduced pressure
  2. customto remove THF
  3. custombefore partitioning between ethyl acetate and water
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe material was then dissolved in DMSO
  8. custompurified in aliquots by preparative HPLC
  9. customThe desired fractions were collected
  10. concentrationconcentrated
  11. customto give a white solid which
  12. washwas washed with ether

Sources & evidence

ORD record
ord-102f7f63ac584b16ad4ba8611f9f5416
Source dataset
uspto-grants-2010_03
Patent number
US07687515B2

Reaction notes

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