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

HRID 2038628Notes

Reaction equation

HRID 2038628 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-f5e6e469bb704564aa82efacae30b739
Source dataset
uspto-grants-2013_11
Patent number
US08575391B2

Reaction notes

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