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

HRID 1672937Notes

Reaction equation

HRID 1672937 reaction equation
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

Participants

5

Reactant 2

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

Product 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 hydrochlorideYield 12%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-63214ef6180b467f90c092311a070fb4
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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