Sodium cyanoborohydride → 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-oxo-piperidin-1-ylmethyl)-benzamide

HRID 20774

Reaction equation

HRID 20774 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9]C)=O.C([BH3-])#N.[Na+].[F:15][C:16]1[C:17]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=2[F:40])=[C:18]([CH:26]=[C:27]([CH:30]=O)[C:28]=1[F:29])[C:19]([NH:21][O:22][CH2:23][CH2:24][OH:25])=[O:20]>O1CCCC1>[F:15][C:16]1[C:17]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([I:39])=[CH:35][C:34]=2[F:40])=[C:18]([CH:26]=[C:27]([CH2:30][N:2]2[CH2:3][CH2:4][CH2:5][CH2:6][C:7]2=[O:9])[C:28]=1[F:29])[C:19]([NH:21][O:22][CH2:23][CH2:24][OH:25])=[O:20]

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 13672034Methyl 5-aminopentanoate hydrochlorideHCID 231323883,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide

Product 1

HCID 115342093,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-oxo-piperidin-1-ylmethyl)-benzamideYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 5-amino-pentanoate hydrochloride {see J. Org. Chem. (1968) 1581} (128 mg, 0.178 mmol) and sodium cyanoborohydride (45 mg, 0.718 mmol) were added to a solution of 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-formyl-N-(2-hydroxy-ethoxy)-benzamide (115 mg, 0.239 mmol) obtained in Step F of Example 1 in tetrahydrofuran (anhydrous, 4.0 mL). The mixture was stirred at room temperature for 1.5 hours. Then, the reaction vessel was equipped with a reflux condenser, and the mixture was heated at 60° C. for 2 days. After completion of the reaction, the reaction mixture was extracted with ethyl acetate, and the organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 4% methanol/methylene chloride as an eluent) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-oxo-piperidin-1-ylmethyl)-benzamide (Compound H-4, 42.7 mg, 37%) as a white solid.

Workup

  1. customThen, the reaction vessel was equipped with a reflux condenser
  2. temperaturethe mixture was heated at 60° C. for 2 days
  3. customAfter completion of the reaction
  4. extractionthe reaction mixture was extracted with ethyl acetate
  5. washthe organic layer was washed sequentially with water and saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resultant residue was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 4% methanol/methylene chloride as an eluent)

Sources & evidence

ORD record
ord-e1a179c48aa24e148150009a12a9ba8b
Source dataset
uspto-grants-2010_06
Patent number
US07745663B2

Linked notes

Loading…