Triethylamine → (S)-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamide

HRID 391517Notes

Reaction equation

HRID 391517 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].C(N(CC)CC)C.[CH3:27][Si:28]([C:31]#[CH:32])([CH3:30])[CH3:29]>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>[CH3:18][S@:10](=[O:17])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[N:9][C:7](=[O:8])[C:6]1[CH:19]=[C:2]([C:32]#[C:31][Si:28]([CH3:30])([CH3:29])[CH3:27])[CH:3]=[N:4][CH:5]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 86629466(S)-5-bromo-N-[methyl(oxido)phenyl--sulfanylidene]nicotinamide

Product 1

HCID 24953135(S)-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamideYield 63%

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 10.0 mL DMF at room temperature was added (S)-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (1.02 g, 3.0 mmol), triethylamine (1.3 mL, 9.0 mmol), trimethylsilylacetylene (0.83 mL, 6.0 mmol), and dichlorobis(triphenylphosphine)palladium(II) (211 mg, 0.3 mmol). After 15 minutes added copper(I) iodide (29 mg, 0.15 mmol) and continued reaction for 4 hours. The reaction was then partitioned between EtOAc and H2O. The EtOAc layer was washed with saturated NaHCO3, brine, dried with anhydrous Na2SO4 and rotary evaporated to 20 ml volume. The solution was placed overnight in the refrigerator and the resulting solid filtered and rinsed with 40% EtOAc/hexane to give The title compound (674 mg) as a tan solid. The filtrate was evaporated and purified by chromatography (silica gel, eluting with hexane/EtOAc) to give an additional 301 mg of the title compound. The product lots were combined and purified by chromatography (silica gel, eluting with to hexane/EtOAc) to give the title compound as a tan solid (959 mg, 90%).

Workup

  1. customreaction for 4 hours
  2. customThe reaction was then partitioned between EtOAc and H2O
  3. washThe EtOAc layer was washed with saturated NaHCO3, brine
  4. dry with materialdried with anhydrous Na2SO4
  5. customrotary evaporated to 20 ml volume
  6. filtrationthe resulting solid filtered
  7. washrinsed with 40% EtOAc/hexane

Sources & evidence

ORD record
ord-0c2594e2a48f45ba9796720700baa60b
Source dataset
uspto-grants-2013_02
Patent number
US08383825B2

Reaction notes

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