Dichloroacetic Acid → 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methylcarbamoylmethoxyamino-methyl)-benzamide

HRID 20738

반응식

HRID 20738 반응식
[F:1][C:2]1[C:3]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])=[C:4]([CH:12]=[C:13](/[CH:16]=[N:17]/[O:18][CH2:19][C:20](=[O:23])[NH:21][CH3:22])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].ClC(Cl)C(O)=O>C(Cl)Cl>[F:1][C:2]1[C:3]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([I:31])=[CH:27][C:26]=2[F:32])=[C:4]([CH:12]=[C:13]([CH2:16][NH:17][O:18][CH2:19][C:20](=[O:23])[NH:21][CH3:22])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

참가 물질

4

반응물 2

HCID 6597Dichloroacetic Acid2회HCID 231323223,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(E)-[2-(methylamino)-2-oxoethoxy]iminomethyl]benzamide

생성물 1

HCID 116210943,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methylcarbamoylmethoxyamino-methyl)-benzamide수율 54.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (E)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-[methylcarbamoylmethoxyimino-methyl]-benzamide (69.8 mg, 0.12 mmol) obtained in Step C in methylene chloride (15 ml) were added borane-pyridine complex (199 μl, 1.92 mmol) and dichloroacetic acid (162 μl, 1.92 mmol) at room temperature, and the mixture was stirred for 3.5 days. Additional borane-pyridine complex (199 μl, 1.92 mmol) and dichloroacetic acid (162 μl, 1.92 mmol) were added, and the mixture was stirred for 1 day. The reaction mixture was diluted with methylene chloride (20 ml), and washed with saturated brine (2×20 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resultant residue was purified by preparative TLC (EtOAc/MeOH (9:1)) to give 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(methylcarbamoylmethoxyamino-methyl)-benzamide (36.9 mg, 53%) as a colorless oil.

후처리

  1. stirringthe mixture was stirred for 1 day
  2. washwashed with saturated brine (2×20 ml)
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resultant residue was purified by preparative TLC (EtOAc/MeOH (9:1))

출처 및 근거

ORD 기록
ord-c841ec391b9040febf2581ae3242aa67
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745663B2

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