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Diisopropyl Ether → 4-Trimethylsilanylethynyl-thiazole-2-carboxylic acid-(6-acetyl-3-methoxy-2-methyl-phenyl)-amide

HRID 880741
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HRID 880741 반응식
[C:1]([C:4]1[C:9]([NH:10][C:11]([C:13]2[S:14][CH:15]=[C:16](Br)[N:17]=2)=[O:12])=[C:8]([CH3:19])[C:7]([O:20][CH3:21])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[C:22]([Si:24]([CH3:27])([CH3:26])[CH3:25])#[CH:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(C)C)(C)C>C(NC(C)C)(C)C.[Cu](I)I.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>[C:1]([C:4]1[C:9]([NH:10][C:11]([C:13]2[S:14][CH:15]=[C:16]([C:23]#[C:22][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:17]=2)=[O:12])=[C:8]([CH3:19])[C:7]([O:20][CH3:21])=[CH:6][CH:5]=1)(=[O:3])[CH3:2]
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반응물 4

HCID 7914Diisopropyl EtherHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 56605318N-(6-acetyl-3-methoxy-2-methylphenyl)-4-bromo-1,3-thiazole-2-carboxamide

생성물 1

HCID 672140214-Trimethylsilanylethynyl-thiazole-2-carboxylic acid-(6-acetyl-3-methoxy-2-methyl-phenyl)-amide수율 84%

시약·촉매·용매 3

HCID 83717Copper iodide촉매
HCID 178418476HCID 178418476, 화합물촉매
HCID 7912Diisopropylamine용매

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온도
80 °C

실험 절차

To a suspension of compound 207b (10.12 g, 1 eq.) in diisopropylamine (40 mL) were added ethynyltrimethylsilane (5.7 mL, 1.5 eq.), triphenylphosphine (0.283 g, 0.04 eq.), copper iodide (0.206 g, 0.04 eq.), and PdCl2(PPh3)2 (0.38 g, 0.02 eq.). The mixture was stirred under nitrogen and heated to 80° C. (external temperature). After 10 min, the solvent was refluxed, and the mixture solidified and turned brown grey. DIPA (20 mL) was added to solubilize the reaction mixture. After 2.5 hrs, the reaction was complete and the mixture cooled down to room temperature. Diisopropyl ether (20 mL) was added. A grey solid was recovered by filtration, dissolved in dichloromethane, and washed with water. The organic layer was dried over Na2SO4, filtered, and concentrated to give black solid. The residue was purified by chromatography on silica gel (dichloromethane) to give compound 208b as a beige solid in 84% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 0.29 (s, 9H), 2.13 (s, 3H), 2.58 (s, 3H), 3.93 (s, 3H), 6.81 (d, J=8.78 Hz, 1H), 7.69 (s, 1H), 7.76 (d, J=8.78 Hz, 1H), 11.05 (s, 1H).

후처리

  1. temperaturethe solvent was refluxed
  2. additionDIPA (20 mL) was added
  3. waitAfter 2.5 hrs
  4. temperaturethe mixture cooled down to room temperature
  5. filtrationA grey solid was recovered by filtration
  6. dissolutiondissolved in dichloromethane
  7. washwashed with water
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give black solid
  12. customThe residue was purified by chromatography on silica gel (dichloromethane)

출처 및 근거

ORD 기록
ord-c5047986935045fd80e931a251674fb4
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08993595B2

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