Iodoacetamide → 2-(3-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetamide

HRID 244394Notes

Reaction equation

HRID 244394 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].[OH-].[K+].I[CH2:35][C:36]([NH2:38])=[O:37]>CN(C=O)C.[Cl-].[NH4+]>[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]([NH2:38])=[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

6

Reactant 3

HCID 3727IodoacetamideHCID 14797Potassium HydroxideHCID 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 249594542-(3-{2,2,2-Trifluoro-1-[1-(4-fluorophenyl)-1H-indazol-5-yl]-1-hydroxyethyl}pyrrolo[2,3-b]pyridin-1-yl)acetamideYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 60 mg (0.14 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 21 mg (0.27 mmol) of powdered KOH followed by 51 mg (0.28 mmol) of iodoacetamide. The mixture stirred for 30 minutes, and was then diluted with saturated aqueous ammonium chloride and extracted with three 7 mL portions of ethyl acetate. The combined organic layers were washed with two 7 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel using dichloromethane to load the sample and then eluting with dichloromethane and then ethyl acetate. The material from the column was triturated with ether-hexanes and dried under house vacuum at 80° C. for 2 hours to afford 21 mg (30%) of the title compound. MS m/z 484.28 (MH+).

Workup

  1. extractionextracted with three 7 mL portions of ethyl acetate
  2. washThe combined organic layers were washed with two 7 mL portions of brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was chromatographed on silica gel
  7. washeluting with dichloromethane
  8. customThe material from the column was triturated with ether-hexanes
  9. customdried under house vacuum at 80° C. for 2 hours

Sources & evidence

ORD record
ord-d9fc076c680743b6951fb548ea3436bb
Source dataset
uspto-grants-2014_02
Patent number
US08658637B2

Reaction notes

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