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

HRID 388652
ノート
印刷プレビュー

反応式

HRID 388652 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒
HCID 178418476HCID 178418476、化合物触媒
HCID 7912Diisopropylamine溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-e34ff56138f14efc9a25b91ffa09a77d
出典データセット
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08377962B2

反応ノート

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