Triethylamine → (R)-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide

HRID 391522Notes

Reaction equation

HRID 391522 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:19]=1)[C:7]([N:9]=[S@:10]([CH3:18])(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].[OH:20][C:21]1[CH:22]=[C:23]([C:27]#[CH:28])[CH:24]=[CH:25][CH:26]=1.C(N(CC)CC)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C=O)C>[OH:20][C:21]1[CH:22]=[C:23]([C:27]#[C:28][C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH:19]=2)[C:7]([N:9]=[S@:10]([CH3:18])(=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 139144m-Ethynylphenol2×HCID 57657962HCID 57657962, compound

Product 1

HCID 86629467(R)-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamideYield 32%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a degassed solution of 2.0 mL DMF at room temperature containing (R)-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (105 mg, 0.31 mmol), 3-hydroxyphenylacetylene (73 mg, 0.62 mmol) and triethylamine (0.13 mL, 0.93 mmol) was added dichlorobis(triphenylphosphine)palladium(II) (22 mg, 0.031 mmol) and copper(I)iodide (3 mg, 0.016 mmol). The reaction was stirred at room temperature for 1.5 hours. Additional 3-hydroxyphenylacetylene was added (30 mg, 0.25 mmol) and the reaction was stirred at room temperature for an additional 3.5 hours. After proceeding for 5 hours the reaction was partitioned between EtOAc and H2O and the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and concentrated. The residual dark oil was purified by chromatography (silica gel, CHCl3/EtOAc) and the product containing fractions were concentrated. The resulting solid was triturated with EtOAc/hexane to give the title compound as an off-white solid (37 mg, 32%).

Workup

  1. stirringthe reaction was stirred at room temperature for an additional 3.5 hours
  2. waitAfter proceeding for 5 hours
  3. customthe reaction was partitioned between EtOAc and H2O
  4. washthe EtOAc layer washed with H2O, brine
  5. dry with materialdried with anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe residual dark oil was purified by chromatography (silica gel, CHCl3/EtOAc)
  8. additionthe product containing fractions
  9. concentrationwere concentrated
  10. customThe resulting solid was triturated with EtOAc/hexane

Sources & evidence

ORD record
ord-7311e1b84c9b47acaba717dfaaebb53f
Source dataset
uspto-grants-2013_02
Patent number
US08383825B2

Reaction notes

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