Dichloromethane → 5-[(2-acetylamino-ethoxyamino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide

HRID 20752Notes

Reaction equation

HRID 20752 reaction equation
[C:1]([NH:4][CH2:5][CH2:6][O:7]/[N:8]=[CH:9]/[C:10]1[C:11]([F:33])=[C:12]([F:32])[C:13]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])=[C:14]([CH:22]=1)[C:15]([NH:17][O:18][CH2:19][CH2:20][OH:21])=[O:16])(=[O:3])[CH3:2].ClCCl.ClC(Cl)C(O)=O.C(=O)(O)[O-].[Na+]>O>[C:1]([NH:4][CH2:5][CH2:6][O:7][NH:8][CH2:9][C:10]1[C:11]([F:33])=[C:12]([F:32])[C:13]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([I:30])=[CH:26][C:25]=2[F:31])=[C:14]([CH:22]=1)[C:15]([NH:17][O:18][CH2:19][CH2:20][OH:21])=[O:16])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6597Dichloroacetic AcidHCID 516892Sodium BicarbonateHCID 231323375-[(E)-2-acetamidoethoxyiminomethyl]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamide

Product 1

HCID 116571505-[(2-acetylamino-ethoxyamino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamideYield 76.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To (E)-5-[(2-acetylamino-ethoxyimino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (57.6 mg, 99.3 μmol) obtained in Step D was added dichloromethane (2.5 ml). The mixture was stirred at room temperature, and borane-pyridine complex (80 μl, 0.79 mmol) and dichloroacetic acid (67 μl, 0.80 mmol) were added thereto. After stirring for 3 hours, water (10 ml) and saturated aqueous sodium bicarbonate (2 ml) were added to the reaction mixture, which was then extracted with methylene chloride (15 ml and 2×8 ml). The combined organic layers were washed with aqueous sodium bicarbonate (8 ml) and saturated aqueous sodium chloride (8 ml), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methylene chloride/methanol (10:1)) to give 5-[(2-acetylamino-ethoxyamino)-methyl]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (Compound C-7, 44.0 mg, 76%).

Workup

  1. stirringAfter stirring for 3 hours
  2. extractionwas then extracted with methylene chloride (15 ml and 2×8 ml)
  3. washThe combined organic layers were washed with aqueous sodium bicarbonate (8 ml) and saturated aqueous sodium chloride (8 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (methylene chloride/methanol (10:1))

Sources & evidence

ORD record
ord-55796ef0242a4b59b1867e851185c1c7
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

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