Iodoacetamide → 2-{3-[2,2,2-Trifluoro-1-hydroxy-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethyl]indol-1-yl}acetamide

HRID 244411Notes

Reaction equation

HRID 244411 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1)([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)[N:9]=[CH:8]2)[OH:4].[OH-].[K+].I[CH2:34][C:35]([NH2:37])=[O:36]>CN(C=O)C>[F:30][C:2]([F:1])([F:29])[C:3]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]([CH2:34][C:35]([NH2:37])=[O:36])[CH:21]=1)([OH:4])[C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1)[N:9]=[CH:8]2

Participants

5

Reactant 3

HCID 3727IodoacetamideHCID 14797Potassium HydroxideHCID 249609182,2,2-trifluoro-1-(1H-indol-3-yl)-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethanol

Product 1

HCID 249609192-{3-[2,2,2-Trifluoro-1-hydroxy-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethyl]indol-1-yl}acetamideYield 39.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a chilled (0° C.) solution of 45 mg (0.11 mmol) of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-(1-pyridin-3-yl-1H-indazol-5-yl)ethanol in 5 mL of DMF was added 13 mg (0.17 mmol) of powder KOH followed by 31 mg (0.17 mmol) of iodoacetamide. The mixture was stirred over night at room temperature, poured onto ice water and extracted with three 20 mL portions of ethyl acetate. The combined organic layers were dried over sodium sulfate, adsorbed on to silica gel and purified by Combiflash chromatography using EtOAc/hexanes (0-80% gradient, product eluted at 40% EtOAc) to provide a colorless film. The material from the column was crystallized from EtOAc-hexanes to afford 20 mg (39%) of the title compound as a colorless powder.

Workup

  1. additionpoured onto ice water
  2. extractionextracted with three 20 mL portions of ethyl acetate
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. custompurified by Combiflash chromatography
  5. customto provide a colorless film
  6. customThe material from the column was crystallized from EtOAc-hexanes

Sources & evidence

ORD record
ord-fe24cff42f9041a6be5df12104d66299
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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