Triethylamine → (S)-tert-butyl (5-{[5-({[methyl(oxo)phenyl-lambda6-sulfanylidene]amino}carbonyl)pyridin-3-yl]ethynyl}-1,3-thiazol-2-yl)carbamate

HRID 391554Notes

Reaction equation

HRID 391554 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.Br[C:26]1[S:30][C:29]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[N:28][CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.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>[CH3:1][S@:2](=[N:3][C:4]([C:5]1[CH:10]=[C:9]([C:11]#[C:12][C:26]2[S:30][C:29]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[N:28][CH:27]=2)[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 6

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 2724141Tetrabutylammonium FluorideHCID 21300388tert-butyl N-(5-bromo-1,3-thiazol-2-yl)carbamateHCID 57657915N-[methyl(oxo)phenyl-lambda6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamideHCID 178514468HCID 178514468, compound

Product 1

HCID 24954183(S)-tert-butyl (5-{[5-({[methyl(oxo)phenyl-lambda6-sulfanylidene]amino}carbonyl)pyridin-3-yl]ethynyl}-1,3-thiazol-2-yl)carbamateYield 18%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of N-[methyl(oxo)phenyl-λ6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamide (73 mg, 0.21 mmol), tert-butyl (5-bromo-1,3-thiazol-2-yl)carbamate (74 mg, 0.27 mmol), dichlorobis(triphenylphosphine)palladium(II) (14 mg, 0.02 mmol), triphenylphosphine (2.7 mg, 0.004 mmol) and triethylamine (0.071 mL, 0.51 mmol) in 1.8 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. While stirring the mixture at room temperature, tetrabutylammonium fluoride (1.0 M in THF, 0.21 mL) was added over 2.5 minutes. After 5 minutes the reaction was heated at 60° C. for 2 hours. The reaction was partitioned between EtOAc and H2O and the EtOAc layer washed with H2O, aqueous HCl, saturated NaHCO3 solution, brine, dried with anhydrous Na2SO4 and concentrated. The brown oil was chromatographed eluting with hexane/acetone and the product containing fractions were concentrated to give the title compound as a light yellow solid (17 mg, 18%).

Workup

  1. customwas degassed
  2. temperatureAfter 5 minutes the reaction was heated at 60° C. for 2 hours
  3. customThe reaction was partitioned between EtOAc and H2O
  4. washthe EtOAc layer washed with H2O, aqueous HCl, saturated NaHCO3 solution, brine
  5. dry with materialdried with anhydrous Na2SO4
  6. concentrationconcentrated
  7. customThe brown oil was chromatographed
  8. washeluting with hexane/acetone
  9. additionthe product containing fractions
  10. concentrationwere concentrated

Sources & evidence

ORD record
ord-4043e9f475ff470ab1dcf8d3eaecee2d
Source dataset
uspto-grants-2013_02
Patent number
US08383825B2

Reaction notes

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