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

HRID 391554노트

반응식

HRID 391554 반응식
[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

참가 물질

10

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-4043e9f475ff470ab1dcf8d3eaecee2d
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08383825B2

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