3-Ethynylpyridine → HCID 49802276, compound

HRID 1159296Notes

Reaction equation

HRID 1159296 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-d1a510b74bd747a6a0ba9880c1cb7c5b
Source dataset
uspto-grants-2010_10
Patent number
US07812028B2

Reaction notes

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