Cesium carbonate → 1-{6-[5-(2-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridin-3-yl}-1H-imidazole-4-carbonitrile

HRID 1500347Notes

Reaction equation

HRID 1500347 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]=[N:11][N:10]([CH3:13])[C:9]=1[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19](I)=[CH:18][N:17]=1.[NH:23]1[CH:27]=[C:26]([C:28]#[N:29])[N:25]=[CH:24]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.[Cu-]=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]=[N:11][N:10]([CH3:13])[C:9]=1[CH2:14][O:15][C:16]1[N:17]=[CH:18][C:19]([N:23]2[CH:27]=[C:26]([C:28]#[N:29])[N:25]=[CH:24]2)=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 900206532-[5-(2-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-5-iodo-pyridineHCID 178510437HCID 178510437, compound

Product 1

HCID 727060121-{6-[5-(2-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridin-3-yl}-1H-imidazole-4-carbonitrileYield 39.38%

Reagents, catalysts & solvents 2

HCID 178419072HCID 178419072, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

The mixture of 2-[5-(2-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-5-iodo-pyridine (0.5 g, 1.22 mmol), 1H-imidazole-4-carbonitrile (0.170 g, 1.82 mmol), cesium carbonate (0.79 g, 2.43 mmol), copper(I)oxide (0.017 g, 0.122 mmol), ferric acetylacetonate (0.129 g, 0.365 mmol) in DMF (10 ml) was heated at 90° C. for 20 h. The reaction was monitored by TLC and UPLC. The reaction mixture was concentrated under reduced pressure, water was added and extracted with ethylacetate (3×50 ml). The organic layer was washed with brine (15 ml), dried over Na2SO4 and concentrated under reduced pressure to afford crude mass (500 mg, 109% mass balance). It was purified in grace column using 2% methanol in chloroform as an eluent to furnish desired 1-{6-[5-(2-Fluoro-phenyl)-3-methyl-3H-[1,2,3]triazol-4-ylmethoxy]-pyridin-3-yl}-1H-imidazole-4-carbonitrile (0.180 g, 39.38%) as off-white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, water
  2. additionwas added
  3. extractionextracted with ethylacetate (3×50 ml)
  4. washThe organic layer was washed with brine (15 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto afford crude mass (500 mg, 109% mass balance)
  8. customIt was purified in grace column

Sources & evidence

ORD record
ord-4c8a07f20f5f434291850c2e308cd06b
Source dataset
uspto-grants-2015_12
Patent number
US09206160B2

Reaction notes

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