Methyl iodide → HCID 58382168, compound

HRID 1628032Notes

Reaction equation

HRID 1628032 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[C:10](I)=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([CH3:23])[O:22][CH2:21][CH2:20][O:19]4)=[CH:14][CH:13]=3)[N:8]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:5]2=[N:6][CH:7]=1.[Li][C:33](C)(C)C.CI.[NH4+].[Cl-]>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([CH3:33])=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4([CH3:23])[O:22][CH2:21][CH2:20][O:19]4)=[CH:14][CH:13]=3)[N:8]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 58382134HCID 58382134, compoundHCID 178418306HCID 178418306, compound2×

Product 1

HCID 58382168HCID 58382168, compoundYield 66.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

2-Bromo-7-iodo-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (1.0 g, 1.6 mmol, Preparation #5, Step A) in THF (12 mL) was cooled to about −75° C. then t-BuLi (1.7 M in hexanes, 1.05 mL, 1.79 mmol) was added keeping the temperature about −70 and −75° C. The mixture was stirred for about 5 min at about −75° C. Additional t-BuLi (1.7 M in hexanes, 0.286 mL, 0.487 mmol) was added and the mixture was stirred an additional 15 min. The mixture was treated with MeI (0.461 g, 3.24 mmol) then the temperature of the mixture was raised to about 15° C. over about 10 min. The mixture was stirred at about 20° C. overnight then saturated aqueous NH4Cl (5 mL) was added. The mixture was stirred for about 15 min at about 20° C. then the material was partitioned between EtOAc (50 mL) and water (20 mL). The layers were separated and then the aqueous layer was extracted with EtOAc (10 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified by flash chromatography with a 25 g silica gel column and eluted with 0 to 40% EtOAc/heptane to provide 2-bromo-7-methyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (0.54 g, 66%): LC/MS (Table 2, Method g) Rf=2.25 min; MS m/z 504, 506 (M+H)+.

Workup

  1. customabout −70 and −75° C
  2. stirringthe mixture was stirred an additional 15 min
  3. temperaturethe temperature of the mixture was raised to about 15° C. over about 10 min
  4. stirringThe mixture was stirred at about 20° C. overnight
  5. stirringThe mixture was stirred for about 15 min at about 20° C.
  6. customthe material was partitioned between EtOAc (50 mL) and water (20 mL)
  7. customThe layers were separated
  8. extractionthe aqueous layer was extracted with EtOAc (10 mL)
  9. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe material was purified by flash chromatography with a 25 g silica gel column
  13. washeluted with 0 to 40% EtOAc/heptane

Sources & evidence

ORD record
ord-783368fa09ea407a8283da1d66eb9949
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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