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Trimethylsilylacetylene → 2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-N-(2-hydroxyethoxy)-5-[(E)-(2-hydroxy-2-methylpropoxy)iminomethyl]benzamide

HRID 20755
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 20755
[F:1][C:2]1[C:3]([NH:24][C:25]2[CH:30]=[CH:29][C:28](I)=[CH:27][C:26]=2[F:32])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:17]/[O:18][CH2:19][C:20]([OH:23])([CH3:22])[CH3:21])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].[CH:33]1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)[CH:34]=1.[Na+].[Na+].[Na+].N(CC)(C(C)C)C(C)C.C[Si](C#C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CO.[Cu]I.CCOC(C)=O>[C:33]([C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:3]2[C:2]([F:1])=[C:14]([F:15])[C:13](/[CH:16]=[N:17]/[O:18][CH2:19][C:20]([OH:23])([CH3:22])[CH3:21])=[CH:12][C:4]=2[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6])=[C:26]([F:32])[CH:27]=1)#[CH:34]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 5

HCID 66111TrimethylsilylacetyleneHCID 81531DiisopropylethylamineHCID 2724141Tetrabutylammonium FluorideHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 113875063,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-(2-hydroxy-2-methylpropoxy)iminomethyl]benzamide

Produkt 1

HCID 11363286
2-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-N-(2-hydroxyethoxy)-5-[(E)-(2-hydroxy-2-methylpropoxy)iminomethyl]benzamide
Ausbeute 574,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 887MethanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

(E)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-hydroxy-2-methyl-propoxyimino)-methyl]-benzamide (200 mg, 0.35 mmol), Pd(CH3CN)2Cl2 (4.5 mg, 0.0176 mmol), triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt (25.0 mg, 0.037 mmol), N(iPr)2Et (48.0 mg, 0.37 mmol), trimethylsilyl acetylene (172 mg, 1.76 mmol), and CuI (3.4 mg, 0.0176 mmol) were stirred in MeOH at room temperature for 1 hour, and the solvent was evaporated. The resultant residue was added to THF/H2O containing tetrabutylammonium fluoride (0.35 mmol), and the mixture was stirred for 1 hour. EtOAc was added thereto, and the organic layer was washed with 0.4 N aqueous HCl, dried over Na2SO4, and evaporated. The resultant residue was purified by silica gel chromatography (CH2Cl2/MeOH as a developing solvent) to give a title compound (99 mg).

Aufarbeitung

  1. customthe solvent was evaporated
  2. additionThe resultant residue was added to THF/H2O
  3. washthe organic layer was washed with 0.4 N aqueous HCl
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe resultant residue was purified by silica gel chromatography (CH2Cl2/MeOH as a developing solvent)

Quellen und Nachweise

ORD-Eintrag
ord-b156245e9c11473f9faf23341a2f78ad
Quelldatensatz
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07745663B2

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