Hydrochloric Acid → 3-(2-Aminocyclohexyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol hydrochloride

HRID 1717595ノート

反応式

HRID 1717595 の反応式
C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14]1([OH:37])[CH2:17][N:16]([C:18](=[O:36])[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([F:26])[C:20]=2[NH:27][C:28]2[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=2[F:35])[CH2:15]1)(C)(C)C.[ClH:39]>CO>[NH2:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14]1([OH:37])[CH2:17][N:16]([C:18]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([F:26])[C:20]=2[NH:27][C:28]2[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=2[F:35])=[O:36])[CH2:15]1.[ClH:39].[NH2:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[C:14]1([OH:37])[CH2:17][N:16]([C:18]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([F:26])[C:20]=2[NH:27][C:28]2[CH:33]=[CH:32][C:31]([I:34])=[CH:30][C:29]=2[F:35])=[O:36])[CH2:15]1

参加物

5

反応物 2

HCID 313Hydrochloric Acid2 回HCID 86621268Tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate

生成物 2

HCID 594690123-(2-Aminocyclohexyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-olHCID 670518353-(2-Aminocyclohexyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol hydrochloride収率 12%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒2 回

実験手順

Tert-butyl-2-(1-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzoyl)-3-hydroxyazetidin-3-yl)cyclohexylcarbamate was dissolved in a mixture of methanol (4 mL) and hydrogen chloride (4 M in dioxane) (3 mL). The solution was heated to reflux then cooled to room temperature and stirred for 16 hours. The reaction mixture was concentrated and purified by reverse phase HPLC. The purified fractions were evaporated to dryness and partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford an oil. The residue was taken up in methanol (2 mL) and was added hydrogen chloride (4M in dioxane) (700 μL) and evaporated to dryness to afford the title compound 3-(2-aminocyclohexyl)-1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)azetidin-3-ol hydrochloride (44.7 mg, 12%).

後処理

  1. temperatureThe solution was heated
  2. temperatureto reflux
  3. concentrationThe reaction mixture was concentrated
  4. custompurified by reverse phase HPLC
  5. customThe purified fractions were evaporated to dryness
  6. custompartitioned between ethyl acetate and aqueous sodium bicarbonate
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto afford an oil
  11. customevaporated to dryness

出典と根拠

ORDレコード
ord-8de2349df1754e14980f3cc4da1386ae
出典データセット
uspto-grants-2010_09
特許番号
US07803839B2

反応ノート

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