Triethylamine → (S)-3-{[5-({[methyl(oxo)phenyl-lambda6-sulfanylidene]amino}carbonyl)pyridin-3-yl]ethynyl}benzoic acid

HRID 1099616Notes

Reaction equation

HRID 1099616 reaction equation
[CH3:1][S@:2](=[O:24])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[N:3][C:4](=[O:17])[C:5]1[CH:10]=[C:9]([C:11]#[C:12][Si](C)(C)C)[CH:8]=[N:7][CH:6]=1.I[C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29]([OH:31])=[O:30].C(N(CC)CC)C.[H][H].N#N.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C=O)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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][S@:2](=[N:3][C:4]([C:5]1[CH:10]=[C:9]([C:11]#[C:12][C:26]2[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=2)[C:29]([OH:31])=[O:30])[CH:8]=[N:7][CH:6]=1)=[O:17])(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 120603-Iodobenzoic acidHCID 2724141Tetrabutylammonium FluorideHCID 24953135(S)-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamideHCID 178514468HCID 178514468, compound

Product 1

HCID 24953841(S)-3-{[5-({[methyl(oxo)phenyl-lambda6-sulfanylidene]amino}carbonyl)pyridin-3-yl]ethynyl}benzoic acidYield 74.2%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (S)—N-[methyl(oxo)phenyl-λ6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamide (54 mg, 0.15 mmol), 3-iodobenzoic acid (56 mg, 0.23 mmol), dichlorobis(triphenylphosphine)palladium(II) (11 mg, 0.02 mmol), triphenylphosphine (1.0 mg, 0.004 mmol) and triethylamine (0.073 mL, 0.53 mmol) in 1.5 mL DMF at room temperature was degassed using vacuum and a H2/N2 (1:1) mixture and then copper(I)iodide (2 mg, 0.01 mmol) added. The reaction was heated to 60° C. then tetrabutylammonium fluoride (1.0 M in THF, 0.15 ml) added over 3.5 minutes. After 25 minutes the reaction was partitioned between EtOAc and dilute AcOH. The EtOAc layer was collected and washed with H2O, brine, dried with anhydrous Na2SO4 and concentrated to a yellow solid. The solid was triturated with EtOAc at room temperature to give the title compound as a yellow solid (45 mg, 74%).

Workup

  1. customwas degassed
  2. customAfter 25 minutes the reaction was partitioned between EtOAc and dilute AcOH
  3. customThe EtOAc layer was collected
  4. washwashed with H2O, brine
  5. dry with materialdried with anhydrous Na2SO4
  6. concentrationconcentrated to a yellow solid
  7. customThe solid was triturated with EtOAc at room temperature

Sources & evidence

ORD record
ord-886c02ab281b4313ad2610a01c113b69
Source dataset
uspto-grants-2012_03
Patent number
US08143410B2

Reaction notes

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