Triethylamine → (S)-2-amino-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide

HRID 1099655Notes

Reaction equation

HRID 1099655 reaction equation
[NH2:1][C:2]1[N:19]=[CH:18][C:17](Br)=[CH:16][C:3]=1[C:4]([N:6]=[S@@:7]([CH3:15])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].[OH:21][C:22]1[CH:23]=[C:24]([C:28]#[CH:29])[CH:25]=[CH:26][CH:27]=1.C(N(CC)CC)C>CCOC(C)=O.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>[NH2:1][C:2]1[N:19]=[CH:18][C:17]([C:29]#[C:28][C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([OH:21])[CH:23]=2)=[CH:16][C:3]=1[C:4]([N:6]=[S@@:7]([CH3:15])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 139144m-Ethynylphenol3×HCID 86629471(S)-2-amino-5-bromo-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide

Product 1

HCID 86629470(S)-2-amino-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamideYield 4.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
70 °C

Procedure

To a degassed solution containing (S)-2-amino-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (106 mg, 0.3 mmol) and 3-hydroxyphenylacetylene (50 mg, 0.42 mmol) in 2.0 mL EtOAc at room temperature was added triethylamine (0.13 mL, 0.9 mmol), dichlorobis(triphenylphosphine)palladium(II) (21 mg, 0.03 mmol), and copper(I)iodide (6 mg, 0.03 mmol). The reaction was stirred at 70° C. for 3.3 hours. Additional 3-hydroxyphenylacetylene was added (50 mg, 0.42 mmol) and then again at 5.3 hours (75 mg, 0.63 mmol). The reaction was cooled to room temperature, and after 23 hours additional dichlorobis(triphenylphosphine)palladium(II) (20 mg, 0.03 mmol) was added. The reaction was heated to 60° C. and 3-hydroxyphenylacetylene (120 mg, 1.0 mmol) in 0.7 mL EtOAc (degassed) added dropwise over 7 minutes. The heat was removed after 1 hour and the reaction stirred an additional 22 hours at room temperature. The reaction was dissolved in EtOAc and washed with H2O. The EtOAc layer was extracted with 2% aqueous HCl. The combined acidic aqueous layers were washed with 30% EtOAc/hexane and then made basic with Na2CO3. The basic aqueous layer was extracted with EtOAc. Then the combined organic layers washed with brine, dried with anhydrous Na2SO4 and concentrated. The yellow oil was purified by chromatography (silica gel, CHCl3/EtOAc) to give the title compound as a white solid (5 mg, 4%).

Workup

  1. waitagain at 5.3 hours (75 mg, 0.63 mmol)
  2. temperatureThe reaction was cooled to room temperature
  3. temperatureThe reaction was heated to 60° C.
  4. customThe heat was removed after 1 hour
  5. stirringthe reaction stirred an additional 22 hours at room temperature
  6. dissolutionThe reaction was dissolved in EtOAc
  7. washwashed with H2O
  8. extractionThe EtOAc layer was extracted with 2% aqueous HCl
  9. washThe combined acidic aqueous layers were washed with 30% EtOAc/hexane
  10. extractionThe basic aqueous layer was extracted with EtOAc
  11. washThen the combined organic layers washed with brine
  12. dry with materialdried with anhydrous Na2SO4
  13. concentrationconcentrated
  14. customThe yellow oil was purified by chromatography (silica gel, CHCl3/EtOAc)

Sources & evidence

ORD record
ord-f13437e56c5c49cb9963971a9443294c
Source dataset
uspto-grants-2012_03
Patent number
US08143410B2

Reaction notes

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