Methyl iodide → HCID 58382359, compound

HRID 1628036Notes

Reaction equation

HRID 1628036 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[C:11](I)=[C:10]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([CH3:24])[O:23][CH2:22][CH2:21][O:20]4)=[CH:15][CH:14]=3)[N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:5]2=[N:6][C:7]=1[CH3:8].[Li][CH2:34][CH2:35]CC.CI>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]2[C:11]([CH2:34][CH3:35])=[C:10]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([CH3:24])[O:23][CH2:22][CH2:21][O:20]4)=[CH:15][CH:14]=3)[N:9]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[C:5]2=[N:6][C:7]=1[CH3:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 58382188HCID 58382188, compoundHCID 178418339Butyllithium

Product 1

HCID 58382359HCID 58382359, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

2-Bromo-7-iodo-3-methyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (12.7 g, 20.2 mmol) in THF (200 mL) was cooled to about −75° C. then n-BuLi (1.5 M, 14.8 mL, 22.2 mmol) was added while maintaining the internal temperature of the mixture between −70 and −75° C. The mixture was stirred for about 20 min then the mixture was treated with MeI (6.51 mL, 81 mmol). The cooling bath was removed and replaced with a warm water bath. The temperature of the mixture was raised to about 20° C. over about 10 min. The mixture was stirred at about 20° C. for about 30 min then saturated aqueous NH4Cl (10 mL) was added. The mixture was stirred for about 15 min then concentrated under reduced pressure. The material was partitioned between Et2O (200 mL) and water (100 mL). The organic layer was isolated and the aqueous layer was extracted with Et2O (50 mL). The combined organics were washed with water (50 mL) then brine (50 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was purified with an 80 g silica column and eluted with 85:15 heptane/Et2O to give 2-bromo-7-ethyl-3-methyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine (6.83 g, 64%): LC/MS (Table 2, Method g) Rt=2.17 min; MS m/z 532 (M+H)+.

Workup

  1. temperaturewhile maintaining the internal temperature of the mixture between −70 and −75° C
  2. customThe cooling bath was removed
  3. customreplaced with a warm water bath
  4. stirringThe mixture was stirred at about 20° C. for about 30 min
  5. additionsaturated aqueous NH4Cl (10 mL) was added
  6. stirringThe mixture was stirred for about 15 min
  7. concentrationthen concentrated under reduced pressure
  8. customThe material was partitioned between Et2O (200 mL) and water (100 mL)
  9. customThe organic layer was isolated
  10. extractionthe aqueous layer was extracted with Et2O (50 mL)
  11. washThe combined organics were washed with water (50 mL)
  12. dry with materialbrine (50 mL), dried over anhydrous MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe material was purified with an 80 g silica column
  16. washeluted with 85:15 heptane/Et2O

Sources & evidence

ORD record
ord-13edd52ed3004898bd56886ee253664a
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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