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

HRID 2038631Notes

Reaction equation

HRID 2038631 reaction equation
[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]

Participants

9

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

(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).

Workup

  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)

Sources & evidence

ORD record
ord-a8fb2c19e02c4eab928a827c56d1bc04
Source dataset
uspto-grants-2013_11
Patent number
US08575391B2

Reaction notes

Loading…