Triethylamine → (S)-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]-5-({4-[(2-thienylcarbonyl)amino]phenyl}ethynyl)nicotinamide

HRID 391538Notes

Reaction equation

HRID 391538 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[O:11])=[CH:5][CH:4]=1)#[CH:2].Br[C:18]1[CH:19]=[N:20][CH:21]=[C:22]([CH:35]=1)[C:23]([N:25]=[S@@:26]([CH3:34])(=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24].CCN(CC)CC>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.CCOC(C)=O>[CH3:34][S@:26](=[O:33])([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[N:25][C:23](=[O:24])[C:22]1[CH:35]=[C:18]([C:2]#[C:1][C:3]2[CH:4]=[CH:5][C:6]([NH:9][C:10]([C:12]3[S:13][CH:14]=[CH:15][CH:16]=3)=[O:11])=[CH:7][CH:8]=2)[CH:19]=[N:20][CH:21]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 3411607N-(4-ethynylphenyl)thiophene-2-carboxamideHCID 86629466(S)-5-bromo-N-[methyl(oxido)phenyl--sulfanylidene]nicotinamide

Product 1

HCID 57657851(S)-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]-5-({4-[(2-thienylcarbonyl)amino]phenyl}ethynyl)nicotinamideYield 61%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

In a 4 mL vial, thiophene-2-carboxylic acid (4-ethynyl-phenyl)-amide (0.100 g, 0.443 mmol) and (S)-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (100 mg, 0.295 mmol) were added and dissolved into EtOAc (2 mL). The mixture was then degassed for ˜20 min after which NEt3 (0.141 mL, 1.035 mmol) was added followed by Pd(PPh3)2Cl2 (20.7 mg, 0.0295 mmol) and CuI (2.8 mg, 0.148 mmol). The reaction mixture was allowed to stir at 50° C. for 3 hours after which the reaction mixture was extracted twice with EtOAc (˜5 mL) and of water (˜5 mL). The organic extracts were combined and dried over anhydrous Na2SO4(s) and then concentrated in vacuo. The crude residue was then purified by chromatography (silica gel, gradient elution, 25% EtOAc/hexanes to 100% EtOAc/hexanes). The product containing fractions were concentrated to give the title compound as a tan solid (87 mg, 0.18 mmol, 61%).

Workup

  1. additionwas added
  2. extractionwas extracted twice with EtOAc (˜5 mL) and of water (˜5 mL)
  3. dry with materialdried over anhydrous Na2SO4(s)
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was then purified by chromatography (silica gel, gradient elution, 25% EtOAc/hexanes to 100% EtOAc/hexanes)
  6. additionThe product containing fractions
  7. concentrationwere concentrated

Sources & evidence

ORD record
ord-929ab15a155f4ffd96d62857de77f4bb
Source dataset
uspto-grants-2013_02
Patent number
US08383825B2

Reaction notes

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