Phosphate → 6-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-(4-oxo-butyl)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 216449Notes

Reaction equation

HRID 216449 reaction equation
[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:24]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][C:27]=3[CH3:33])=[C:23]([F:34])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][CH2:17][CH2:18][CH:19]([OH:22])CO)[C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1.C1COCC1.P([O-])([O-])([O-])=O.I([O-])(=O)(=O)=O.[Na+]>C(OCC)(=O)C>[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:24]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][C:27]=3[CH3:33])=[C:23]([F:34])[C:12]3[N:13]=[CH:14][N:15]([CH2:16][CH2:17][CH2:18][CH:19]=[O:22])[C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 1061PhosphateHCID 8028TetrahydrofuranHCID 23667635Sodium periodateHCID 865990166-(4-Bromo-2-methyl-phenylamino)-3-(4,5-dihydroxy-pentyl)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

Product 1

HCID 866171186-(4-Bromo-2-methyl-phenylamino)-7-fluoro-3-(4-oxo-butyl)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amideYield 82.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 6-(4-bromo-2-methyl-phenylamino)-3-(4,5-dihydroxy-pentyl)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide 11m (0.244 g, 0.456 mmol), THF (5 mL) and pH 7 phosphate buffer (3 mL) is added sodium periodate (0.195 g, 0.911 mmol). After 16 hours, the reaction mixture is diluted with ethyl acetate and washed with NaHCO3, and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure to give an orange solid. Purification by FCC eluted with 4:1 methylene chloride/MeOH yields 0.189 g (82%) pure desired product as a yellow solid: MS APCI (+) m/z 505, 503 (M+1 Br pattern) detected; MS APCI (−) m/z 503, 501 (M−1 Br pattern) detected.

Workup

  1. washwashed with NaHCO3, and brine
  2. dry with materialThe organic layer is dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure
  4. customto give an orange solid
  5. customPurification by FCC
  6. washeluted with 4:1 methylene chloride/MeOH

Sources & evidence

ORD record
ord-33a29d9807314cbda24f882a7ef23865
Source dataset
uspto-grants-2012_06
Patent number
US08193229B2

Reaction notes

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