Potassium Iodide → 2-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246111Notes

Reaction equation

HRID 246111 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[C:4]([F:30])[CH:3]=1.[H-].[Na+].Cl.[CH3:34][N:35]([CH2:37][CH2:38]Cl)[CH3:36].[I-].[K+]>CN(C=O)C.C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:27])([CH3:29])[CH3:28])[C:14]4=[N:15][CH:16]=3)=[N:7][N:8]2[CH2:38][CH2:37][N:35]([CH3:36])[CH3:34])=[C:4]([F:30])[CH:3]=1

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 866779472-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 866779502-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeYield 40.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(6-Chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (100 mg, 0.22 mmol) was dissolved in DMF (0.5 ml) and cooled in an ice bath. Sodium hydride (60% dispersion, 22 mg, 0.56 mmol) was carefully added. The mixture was stirred for 10 min then dimethylaminoethyl chloride hydrochloride (36 mg, 0.25 mmol) and potassium iodide (4 mg, 0.022 mmol) were added and the reaction was warmed to room temperature then stirred at 50° C. overnight. After cooling to room temperature, water and ethyl acetate were added to the reaction. The layers were separated and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed water and sodium chloride solution and dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) to give 46 mg (40%) of 2-[6-chloro-1-(2-dimethylamino-ethyl)-4-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde. (M+H)+=517.

Workup

  1. temperaturecooled in an ice bath
  2. stirringthen stirred at 50° C. overnight
  3. temperatureAfter cooling to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice more with ethyl acetate
  6. washThe combined organic layers were washed water and sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. customAfter evaporation
  9. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

Sources & evidence

ORD record
ord-2da012dd715d4c3bbb9210f6be3e0136
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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