N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-1-(2-methoxyethyl)piperidine-4-carboxamide → N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-1-(2-hydroxyethyl)piperidine-4-carboxamide

HRID 1963704Notes

Reaction equation

HRID 1963704 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]1[N:17]([CH3:18])[C:16]2[CH:19]=[CH:20][C:21]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]([CH:33]4[CH2:38][CH2:37][N:36]([CH2:39][CH2:40][O:41]C)[CH2:35][CH2:34]4)=[O:32])[CH:25]=3)=[CH:22][C:15]=2[N:14]=1>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:10])([F:9])[F:11])=[CH:4][C:3]=1[NH:12][C:13]1[N:17]([CH3:18])[C:16]2[CH:19]=[CH:20][C:21]([O:23][C:24]3[CH:29]=[CH:28][N:27]=[C:26]([NH:30][C:31]([CH:33]4[CH2:34][CH2:35][N:36]([CH2:39][CH2:40][OH:41])[CH2:37][CH2:38]4)=[O:32])[CH:25]=3)=[CH:22][C:15]=2[N:14]=1

Participants

3

Reactant 1

HCID 59790258N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-1-(2-methoxyethyl)piperidine-4-carboxamide

Product 1

HCID 59790219N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-1-(2-hydroxyethyl)piperidine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To N-{4-[(2-{[2-fluoro-5-(trifluoromethyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-1-(2-methoxyethyl)piperidine-4-carboxamide (1 eq) in methylene chloride at 78° C. was added 1M borontribromide in methylene chloride (10 eq) and the resulting mixture and the resulting mixture was stirred at −78° C. for 1 h. It was then brought to ambient temperature and stirred for 2 h. LC/MS showed formation of the product. The reaction was quenched with saturated sodium carbonate solution at 0° C. The mixture was concentrated and then brought to pH=9. It was then extracted with ethyl acetate and the organic layer was dried with sodium sulfate and concentrated and purified on preparative chromatography to yield N-{4-[(2-{[2-fluoro-5-(trifluoro-methyl)phenyl]amino}-1-methyl-1H-benzimidazol-5-yl)oxy]pyridin-2-yl}-1-(2-hydroxyethyl)-piperidine-4-carboxamide. MS: MH+=573.6.

Workup

  1. customwas then brought to ambient temperature
  2. stirringstirred for 2 h
  3. customThe reaction was quenched with saturated sodium carbonate solution at 0° C
  4. concentrationThe mixture was concentrated
  5. extractionIt was then extracted with ethyl acetate
  6. dry with materialthe organic layer was dried with sodium sulfate
  7. concentrationconcentrated
  8. custompurified on preparative chromatography

Sources & evidence

ORD record
ord-8861b07f1d964e539b40c70e66b83ba2
Source dataset
uspto-grants-2013_04
Patent number
US08415382B2

Reaction notes

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