Triethylamine → 6-amino-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide

HRID 391562Notes

Reaction equation

HRID 391562 reaction equation
[NH2:1][C:2]1[C:19]([C:20]#[CH:21])=[CH:18][C:5]([C:6]([N:8]=[S@@:9]([CH3:17])(=[O:16])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[CH:4][N:3]=1.I[C:23]1[CH:24]=[C:25]([OH:29])[CH:26]=[CH:27][CH:28]=1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>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>[NH2:1][C:2]1[C:19]([C:20]#[C:21][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=2)=[CH:18][C:5]([C:6]([N:8]=[S:9]([CH3:17])(=[O:16])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 122723-IodophenolHCID 24954186(S)-6-amino-5-ethynyl-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide

Product 1

HCID 576579526-amino-5-[(3-hydroxyphenyl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide

Reagents, catalysts & solvents 3

HCID 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)-6-amino-5-ethynyl-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (60 mg, 0.2 mmol), 3-iodophenol (66 mg, 0.3 mmol), triethylamine (0.07 mL, 0.5 mmol), dichlorobis(triphenylphosphine)palladium(II) (14 mg, 0.02 mmol), triphenylphosphine (1.3 mg, 0.005 mmol) in 1.8 mL DMF at room temperature was degassed using a H2/N2 (1:1) mixture and then copper(I) iodide (2 mg, 0.01 mmol) added. The reaction was heated at 60° C. for 15 minutes and then partitioned between EtOAc and saturated NaHCO3. The EtOAc layer was washed with brine, dried with anhydrous Na2SO4 and rotary evaporated to a brown oil. Before chromatography a different lot of product (23 mg) was added and the combined lots were purified by chromatography (silica gel, EtOAc/EtOH) to the title compound as an off-white solid (91 mg, 89%).

Workup

  1. customwas degassed
  2. custompartitioned between EtOAc and saturated NaHCO3
  3. washThe EtOAc layer was washed with brine
  4. dry with materialdried with anhydrous Na2SO4
  5. customrotary evaporated to a brown oil
  6. additionBefore chromatography a different lot of product (23 mg) was added
  7. customthe combined lots were purified by chromatography (silica gel, EtOAc/EtOH) to the title compound as an off-white solid (91 mg, 89%)

Sources & evidence

ORD record
ord-481ac0eac86544ff9fe2882d9e7da421
Source dataset
uspto-grants-2013_02
Patent number
US08383825B2

Reaction notes

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