Dimethylformamide → 5-[(E)-2-acetamidoethoxyiminomethyl]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamide

HRID 20751Notes

Reaction equation

HRID 20751 reaction equation
[NH2:1][CH2:2][CH2:3][O:4]/[N:5]=[CH:6]/[C:7]1[C:8]([F:30])=[C:9]([F:29])[C:10]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=2[F:28])=[C:11]([CH:19]=1)[C:12]([NH:14][O:15][CH2:16][CH2:17][OH:18])=[O:13].CN(C)C=O.CON(C(C)=O)[C:39](=[O:41])[CH3:40]>CO>[C:39]([NH:1][CH2:2][CH2:3][O:4]/[N:5]=[CH:6]/[C:7]1[C:8]([F:30])=[C:9]([F:29])[C:10]([NH:20][C:21]2[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=2[F:28])=[C:11]([CH:19]=1)[C:12]([NH:14][O:15][CH2:16][CH2:17][OH:18])=[O:13])(=[O:41])[CH3:40]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 538412N,N-Diacetyl-O-methylhydroxylamineHCID 113072055-[(E)-2-aminoethoxyiminomethyl]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamide

Product 1

HCID 231323375-[(E)-2-acetamidoethoxyiminomethyl]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamideYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (E)-5-[(2-amino-ethoxyimino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (8.14 mg, 0.02 mmol) described in Step C in a mixed solvent of dimethylformamide (1 ml) and methanol (5 ml) was added N-methoxydiacetamide (100 mg, 0.76 mmol), and the mixture was stirred at room temperature for 14 hours. After completion of the reaction, the solvent was evaporated under reduced pressure, and the resultant residue was purified with Mega Bond Elut silica gel (Varian, 5 g). (E)-5-[(2-Acetylamino-ethoxyimino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (8.10 mg, 92% yield) was obtained as a pale yellow solid from fractions eluted with 6% methanol/methylene chloride.

Workup

  1. customAfter completion of the reaction
  2. customthe solvent was evaporated under reduced pressure
  3. customthe resultant residue was purified with Mega Bond Elut silica gel (Varian, 5 g)

Sources & evidence

ORD record
ord-fbb797bd6aed47fbb959b19694bdf577
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

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