MeOH tetrahydrofuran → 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-[4-(methylamino)-4-oxobutoxy]iminomethyl]benzamide

HRID 20748Notes

Reaction equation

HRID 20748 reaction equation
[NH2:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][N-:7][CH3:8].[F:9][C:10]1[C:11]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:12]([CH:20]=[C:21]([CH:24]=O)[C:22]=1[F:23])[C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14].[O:35]1CCCC1.CO>>[F:9][C:10]1[C:11]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([I:33])=[CH:29][C:28]=2[F:34])=[C:12]([CH:20]=[C:21](/[CH:24]=[N:1]/[O:2][CH2:3][CH2:4][CH2:5][C:6](=[O:35])[NH:7][CH3:8])[C:22]=1[F:23])[C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14]

Participants

4

Reactant 3

HCID 21899815MeOH tetrahydrofuranHCID 231323883,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamideHCID 866343594-Aminooxybutyl(methyl)azanide

Product 1

HCID 231323693,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-[4-(methylamino)-4-oxobutoxy]iminomethyl]benzamideYield 79%

Procedure

To 4-aminooxy-N-methyl-butylamide (1.79 g, 13.54 mmol) obtained in Step B were added a mixed solvent of tetrahydrofuran/methanol (3:1, 100 ml) and 3,4-difluoro-2-(2-fluoro-4-iodophenylamino-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (5.00 g, 10.41 mmol) obtained in Step F of Example 1, and the mixture was stirred for 13 hours. The reaction mixture was concentrated under reduced pressure to an extent where a little solvent remained, and acetonitrile was added thereto to precipitate the product. This precipitate was filtered, washed with acetonitrile, and dried under reduced pressure to give (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[(3-methylcarbamoyl-propoxyimino)-methyl]-benzamide (4.93 g, 79% yield).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure to an extent where a little solvent
  2. additionacetonitrile was added
  3. customto precipitate the product
  4. filtrationThis precipitate was filtered
  5. washwashed with acetonitrile
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-f0d155eb61924610a358ce60411a3e3d
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Reaction notes

Loading…