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

HRID 20753Notes

Reaction equation

HRID 20753 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][NH:21][C:22](=[O:25])[CH2:23][CH3:24])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].ClC(Cl)C(O)=O.O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[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][NH:21][C:22](=[O:25])[CH2:23][CH3:24])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

Participants

6

Reactant 4

HCID 962WaterHCID 6597Dichloroacetic AcidHCID 516892Sodium BicarbonateHCID 59348010HCID 59348010, compound

Product 1

HCID 115344773,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-propionylamino-ethoxyamino)-methyl]-benzamideYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The oxime, (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-propionylamino-ethoxyimino)-methyl]-benzamide (33.0 mg, 51.0 μmol) obtained in Step A was suspended in methylene chloride (1 ml), and dichloroacetic acid (60 ml) and borane-pyridine complex (70 μl) were added thereto at room temperature. The mixture was stirred at room temperature for 2 hours. Water (6 ml) and aqueous sodium bicarbonate (2 ml) were added to the reaction mixture, which was then extracted with methylene chloride (2×10 ml). The combined organic layers were washed with aqueous sodium bicarbonate (5-fold dilution of saturated solution, 8 ml) and saturated brine (8 ml), dried over sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (methylene chloride/methanol (40:3)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(2-propionylamino-ethoxyamino)-methyl]-benzamide (Compound C-34, 21.6 mg, 71%) as a colorless syrup.

Workup

  1. customat room temperature
  2. extractionwas then extracted with methylene chloride (2×10 ml)
  3. washThe combined organic layers were washed with aqueous sodium bicarbonate (5-fold dilution of saturated solution, 8 ml) and saturated brine (8 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by silica gel column chromatography (methylene chloride/methanol (40:3))

Sources & evidence

ORD record
ord-d715e5dc189044d5b4cc28b6fd8a006f
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

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