Ethyl Acetate → {1-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-acetic acid

HRID 1983555

Reaction equation

HRID 1983555 reaction equation
[CH2:1]([C:5]1[N:6]=[C:7]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=2)[S:8][C:9]=1[CH2:10][N:11]1[C:15]2=[N:16][CH:17]=[C:18]([OH:20])[CH:19]=[C:14]2[CH:13]=[CH:12]1)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[Cs+].[Cs+].C([O:41][C:42](=[O:45])[CH2:43]Br)(C)(C)C.C(OCC)(=O)C>CN(C)C=O>[CH2:1]([C:5]1[N:6]=[C:7]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:30])[F:29])=[CH:23][CH:22]=2)[S:8][C:9]=1[CH2:10][N:11]1[C:15]2=[N:16][CH:17]=[C:18]([O:20][CH2:43][C:42]([OH:45])=[O:41])[CH:19]=[C:14]2[CH:13]=[CH:12]1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 79177tert-Butyl bromoacetateHCID 577130271-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-1H-pyrrolo[2,3-b]pyridin-5-ol

Product 1

HCID 11511486{1-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-acetic acidYield 68.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

200 mg 1-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-1H-pyrrolo[2,3-b]pyridin-5-ol were dissolved in 20 ml dimethylformamide and 300 mg cesium carbonate and 180 mg tert.-butylbromoacetate were added. The reaction mixture was stirred at room temperature for one hour then 100 ml ethyl acetate were added and the mixture was washed five times with portions of 20 ml of water The organic layer was dried over MgSO4 and the solvent removed under reduced pressure. The residue was dissolved in 10 ml dichloromethane and 4 ml trifluoroacetic acid were added. The reaction mixture was stirred at room temperature for three hours then 100 ml toluene were added and the solvents removed under reduced pressure. The residue was purified by RP-HPLC to provide 155 mg {1-[4-Butyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-1H-pyrrolo[2,3-b]pyridin-5-yloxy}-acetic acid as lyophilisate.

Workup

  1. washthe mixture was washed five times with portions of 20 ml of water The organic layer
  2. dry with materialwas dried over MgSO4
  3. customthe solvent removed under reduced pressure
  4. dissolutionThe residue was dissolved in 10 ml dichloromethane
  5. addition4 ml trifluoroacetic acid were added
  6. stirringThe reaction mixture was stirred at room temperature for three hours
  7. addition100 ml toluene were added
  8. customthe solvents removed under reduced pressure
  9. customThe residue was purified by RP-HPLC

Sources & evidence

ORD record
ord-ae39ed152f5745f8b19d8d7ebf5eb0e0
Source dataset
uspto-grants-2009_06
Patent number
US07541464B2

Linked notes

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