Ethyl bromoacetate → (3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetic acid

HRID 244399Notes

Reaction equation

HRID 244399 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]([C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[N:18]=[CH:17]2)([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)[OH:4].[H-].[Na+].Br[CH2:35][C:36]([O:38]CC)=[O:37].[OH-].[Na+]>CN(C=O)C.CO.[Cl-].[NH4+].C(OCC)(=O)C>[F:31][C:2]([F:1])([F:30])[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[CH:11][CH:12]=2)[N:7]([CH2:35][C:36]([OH:38])=[O:37])[CH:6]=1)([C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)[N:18]=[CH:17]2)[OH:4]

Participants

9

Reactant 4

HCID 7748Ethyl bromoacetateHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 249594552,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanol

Product 1

HCID 59437259(3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetic acidYield 88%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 110.0 mg (0.26 mmol) of 2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethanol in 2 mL of DMF was added 16 mg (0.4 mmol) of 60% sodium hydride in mineral oil followed by 32 μL (0.29 mmol) of ethyl bromoacetate. The reaction was monitored by TLC (ethyl acetate) indicating a new polar product. The reaction was diluted with methanol and made basic with 2N aqueous sodium hydroxide. The mixture stirred for 1 hour and was then monitored by LCMS indicating a mass corresponding to the carboxylic acid (M+=485.30). The reaction was diluted with 7 mL of saturated aqueous ammonium chloride and extracted with three 7 mL portions of ethyl acetate. The combined organic layers were washed with three 7 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to afford 110 mg (88%) of (3-{2,2,2-trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetic acid which was used without further purification.

Workup

  1. extractionextracted with three 7 mL portions of ethyl acetate
  2. washThe combined organic layers were washed with three 7 mL portions of brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5b237c0e04b445cdb274f650866e99f8
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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