Sodium hydride → 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

HRID 2204611Notes

Reaction equation

HRID 2204611 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:9]#[C:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]([CH3:22])[CH:12]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[H-].[Na+]>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[CH:9]=[C:10]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13]([CH3:22])[CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 24758Sodium hydride2×HCID 580100635-Bromo-3-((5-methoxy-1-methyl-1H-indol-3-yl)ethynyl)pyrazin-2-amine

Product 1

HCID 498306752-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazineYield 45.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Bromo-3-((5-methoxy-1-methyl-1H-indol-3-yl) ethynyl)pyrazin-2-amine (3.25 g, 9.10 mmol) in DMF (35 mL) was treated with NaH (60% dispersion in mineral oil, 0.36 g, 9.1 mmol). After about 5 h at ambient temperature, the mixture was treated with another portion of NaH (60% dispersion in mineral oil, 0.036 g, 0.91 mmol) and stirred for about 16 h. The mixture was concentrated and stirred with water (50 mL) and EtOAc (40 mL). The mixture was filtered and the solids were washed until an insoluble tar remained. The filtrate layers were separated and the organic layer was dried over anhydrous MgSO4, filtered, and concentrated. The material was dissolved in a minimum amount of warm DMF and purified by silica gel chromatography (120 g silica gel column) eluting with 95:5 DCM/MeOH. The product-containing fractions were combined and concentrated to give an oil which was purified by silica gel chromatography (120 g silica column) eluting with EtOAc. The product-containing fractions were combined and concentrated to give an oily residue which was triturated with EtOAc (20 mL) then filtered to give a yellow solid. The material was dried to give 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine (1.48 g, 45%): LC/MS (Table 2, Method a) Rt=2.50 min; MS m/z: 357 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. stirringstirred with water (50 mL) and EtOAc (40 mL)
  3. filtrationThe mixture was filtered
  4. washthe solids were washed until an insoluble tar
  5. customThe filtrate layers were separated
  6. dry with materialthe organic layer was dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe material was dissolved in a minimum amount of warm DMF
  10. custompurified by silica gel chromatography (120 g silica gel column)
  11. washeluting with 95:5 DCM/MeOH
  12. concentrationconcentrated
  13. customto give an oil which
  14. customwas purified by silica gel chromatography (120 g silica column)
  15. washeluting with EtOAc
  16. concentrationconcentrated
  17. customto give an oily residue which
  18. customwas triturated with EtOAc (20 mL)
  19. filtrationthen filtered
  20. customto give a yellow solid
  21. customThe material was dried

Sources & evidence

ORD record
ord-4f25f43e106749e89b0b983132b1c5b8
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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