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

HRID 20774

反応式

HRID 20774 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-e1a179c48aa24e148150009a12a9ba8b
出典データセット
uspto-grants-2010_06
特許番号
US07745663B2

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