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

HRID 20755

反応式

HRID 20755 の反応式
[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]

参加物

9

反応物 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

生成物 1

HCID 113632862-(4-ethynyl-2-fluoroanilino)-3,4-difluoro-N-(2-hydroxyethoxy)-5-[(E)-(2-hydroxy-2-methylpropoxy)iminomethyl]benzamide収率 574.9%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(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).

後処理

  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)

出典と根拠

ORDレコード
ord-b156245e9c11473f9faf23341a2f78ad
出典データセット
uspto-grants-2010_06
特許番号
US07745663B2

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