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

HRID 2038625Notes

Reaction equation

HRID 2038625 reaction equation
[F:1][C:2]1[C:3]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:17]/[O:18][CH2:19][CH2:20][CH2:21][C:22](=[O:25])[NH:23][CH3:24])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].ClCCl.ClC(Cl)C(O)=O>C(OCC)(=O)C>[F:1][C:2]1[C:3]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:4]([CH:12]=[C:13]([CH2:16][NH:17][O:18][CH2:19][CH2:20][CH2:21][C:22](=[O:25])[NH:23][CH3:24])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6597Dichloroacetic AcidHCID 231323693,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-[4-(methylamino)-4-oxobutoxy]iminomethyl]benzamide

Product 1

HCID 115924153,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylcarbamoyl-propoxyamino)-methyl]-benzamideYield 65%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylcarbamoyl-propoxyimino)-methyl]-benzamide (50 mg, 0.084 mmol) obtained in Step C was added dichloromethane (6 ml). The mixture was stirred at room temperature, and borane-pyridine complex (67 μl, 0.673 mmol) and dichloroacetic acid (55 μl, 0.673 mmol) were added thereto. After stirring for 14 hours, the reaction mixture was diluted with ethyl acetate, and washed with purified water and saturated aqueous sodium chloride. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylcarbamoyl-propoxyamino)-methyl]-benzamide (Compound C-21, 32 mg, 65% yield).

Workup

  1. stirringAfter stirring for 14 hours
  2. washwashed with purified water and saturated aqueous sodium chloride
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f9c3a402f0344070aa44869a957daf6c
Source dataset
uspto-grants-2013_11
Patent number
US08575391B2

Reaction notes

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