Sodium periodate → HCID 86634367, compound

HRID 2038653Notes

Reaction equation

HRID 2038653 reaction equation
I([O-])(=O)(=O)=[O:2].[Na+].[C:7]([NH:11][CH2:12][C:13]1[C:14]([F:43])=[C:15]([F:42])[C:16]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([I:40])=[CH:36][C:35]=2[F:41])=[C:17]([CH:32]=1)[C:18]([NH:20][O:21][CH2:22][CH2:23][O:24][Si:25]([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26])=[O:19])(=[O:10])[CH:8]=C>O1CCCC1.O.[Os](=O)(=O)(=O)=O>[C:28]([Si:25]([CH3:27])([CH3:26])[O:24][CH2:23][CH2:22][O:21][NH:20][C:18](=[O:19])[C:17]1[CH:32]=[C:13]([CH2:12][NH:11][C:7](=[O:10])[CH:8]=[O:2])[C:14]([F:43])=[C:15]([F:42])[C:16]=1[NH:33][C:34]1[CH:39]=[CH:38][C:37]([I:40])=[CH:36][C:35]=1[F:41])([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 2

HCID 23667635Sodium periodateHCID 59348032HCID 59348032, compound

Product 1

HCID 86634367HCID 86634367, compound

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Aqueous osmium tetroxide (4%, 0.1 mL) and sodium metaperiodate (12 mg, 0.056 mmol) were added to a solution of 5-(acryloylamino-methyl)-N-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (7.3 mg, 0.011 mmol) obtained in Step B in tetrahydrofuran (4 mL) and water (1 mL). The mixture was stirred for 3 hours. After the disappearance of the starting material was confirmed by LC/MS, the reaction mixture was extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give N-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-oxo-acetylamino)-methyl]-benzamide. Subsequently, this was dissolved in methanol (2.0 mL). Sodium borohydride (3 mg, 0.079 mmol) was added to this solution at room temperature, and the mixture was stirred for 1 hour. 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 evaporated under reduced pressure. The resultant crude product was purified by silica gel flash chromatography (Mega Bond Elut, Varian, 60% ethyl acetate/hexane as an eluent) to give N-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-5-[(2-hydroxy-acetylamino)-methyl]-benzamide (4.34 mg, 60% in 2 steps) as a pale yellow solid.

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. washThe organic layer was washed sequentially with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d71d844ff17540dfb93052fe5ecedc13
Source dataset
uspto-grants-2013_11
Patent number
US08575391B2

Reaction notes

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