3-Ethynylpyridine → HCID 49802276, compound

HRID 1929900Notes

Reaction equation

HRID 1929900 reaction equation
[CH:1]1([C@:4]([OH:28])([CH3:27])[CH2:5][NH:6][C:7]([C:9]2[CH:14]=[N:13][C:12](Br)=[C:11]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[N:10]=2)=[O:8])[CH2:3][CH2:2]1.[C:29]([C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1)#[CH:30]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]1([C@:4]([OH:28])([CH3:27])[CH2:5][NH:6][C:7]([C:9]2[CH:14]=[N:13][C:12]([CH2:30][CH2:29][C:31]3[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=3)=[C:11]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=3)[N:10]=2)=[O:8])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 1860033-EthynylpyridineHCID 86619574HCID 86619574, compound

Product 1

HCID 49802276HCID 49802276, compound

Reagents, catalysts & solvents 1

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst

Procedure

To a solution of 0.1 g 5-bromo-6-(4-trifluoromethoxy-phenyl)-pyrazine-2-carboxylic acid ((R)-2-cyclopropyl-2-hydroxy-propyl)-amide in 2.0 ml of TEA is added at room temperature 0.015 g of bis (triphenylphosphine) palladium(II) chloride, 0.002 g cuprous iodide and 0.034 g meta-ethynylpyridine. The mixture is treated at 100° C., 1½ hours at the microwave. The starting material is consumed, as evidenced by HPLC. To the mixture is 1N HCl solution in water and ethyl acetate. The organic layer is washed with sodium bicarbonate and sodium chloride 10% solution in water. The residue is purified by chromatography in silica gel. The intermediate was hydrogenated under a hydrogen atmosphere in the presence of palladium on charcoal to yield after filtration and evaporation of the solvent the title compound as off-white oil, MS (ISP) 487.3 (M+H)+.

Workup

  1. additionThe mixture is treated at 100° C., 1½ hours at the microwave
  2. customThe starting material is consumed
  3. washThe organic layer is washed with sodium bicarbonate and sodium chloride 10% solution in water
  4. customThe residue is purified by chromatography in silica gel
  5. customto yield
  6. filtrationafter filtration and evaporation of the solvent the title compound as off-white oil, MS (ISP) 487.3 (M+H)+

Sources & evidence

ORD record
ord-f9702fd55ca0447e992a56ef4ec01454
Source dataset
uspto-grants-2012_05
Patent number
US08188093B2

Reaction notes

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