Methyl iodide → 2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246068Notes

Reaction equation

HRID 246068 reaction equation
[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4]([C:12]1[N:13]=[C:14]3[C:20]([CH:21]=[O:22])=[CH:19][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:15]3=[N:16][CH:17]=1)=[N:5][NH:6]2.[H-].[Na+].I[CH3:34]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[C:4]([C:12]1[N:13]=[C:14]3[C:20]([CH:21]=[O:22])=[CH:19][N:18]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:15]3=[N:16][CH:17]=1)=[N:5][N:6]2[CH3:34]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 866779412-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 866779422-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeYield 24.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (890 mg, 2.1 mmol) in DMF (9 ml) at 0° C. was added sodium hydride (60% in mineral oil, 279 mg, 2.49 mmol). The reaction mixture was stirred at 0° C. for 10 min then iodomethane (0.18 ml, 2.9 mmol) was slowly added. The mixture was stirred at 0° C. for 30 min then at room temperature for 30 min. The reaction was quenched with sat'd NH4Cl, diluted with water and extracted with EtOAc (2×). The combined organics were washed with sat LiCl and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane to provide 226 mg (22%) of 2-(4,6-difluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a yellow solid.

Workup

  1. stirringThe mixture was stirred at 0° C. for 30 min
  2. waitat room temperature for 30 min
  3. customThe reaction was quenched with sat'd NH4Cl
  4. additiondiluted with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organics were washed with sat LiCl and brine
  7. dry with materialthen dried over MgSO4
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane

Sources & evidence

ORD record
ord-ef354f6a626a4608a336bcc8d79d2d95
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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