Iodine → HCID 58382134, compound

HRID 1628005Notes

Reaction equation

HRID 1628005 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[CH:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([CH3:22])[O:21][CH2:20][CH2:19][O:18]4)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.C([Si](C)(C)C)#C.BrC1C(N)=NC=C(Br)N=1.[OH-].[K+].[I:40]I.[H-].[Na+].[CH3:44][Si:45]([CH2:48][CH2:49][O:50][CH2:51]Cl)([CH3:47])[CH3:46]>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([I:40])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:17]4([CH3:22])[O:21][CH2:20][CH2:19][O:18]4)=[CH:15][CH:16]=3)[N:8]([CH2:51][O:50][CH2:49][CH2:48][Si:45]([CH3:47])([CH3:46])[CH3:44])[C:5]2=[N:6][CH:7]=1

Participants

9

Reactant 7

HCID 807IodineHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 66111TrimethylsilylacetyleneHCID 6200042-Amino-3,5-dibromopyrazineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 58382385HCID 58382385, compound

Product 1

HCID 58382134HCID 58382134, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Bromo-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5H-pyrrolo[2,3-b]pyrazine (15.5 g, 43.0 mmol, prepared using A from Preparation #4 with ethynyltrimethylsilane, Q, A with 3,5-dibromopyrazin-2-amine, and B) in DMF (200 mL) was stirred for about 15 min at rt. The mixture was treated with powdered KOH (2.90 g, 51.6 mmol), then iodine (11.3 g, 44.4 mmol) was added in two roughly equal portions over about 15 min then the mixture was stirred for about 2 h at rt. To the mixture was added 60 wt % NaH (2.07 g, 51.6 mmol) in two roughly equal portions then stirred for about 10 min at rt. The mixture was cooled to about 0° C. then SEMCl (8.01 mL, 45.2 mmol) was added over about 10 min. After stirring for about 10 min at about 0° C. the mixture was allowed to warm to rt. After about 1 h the mixture was concentrated under reduced pressure then partitioned between EtOAc (300 mL) and water (200 mL). The organic layer was washed with saturated aqueous NaCl (100 mL) then the combined aqueous layers were extracted with EtOAc (100 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. The material was purified on two successive 120 g silica columns with 8:2 heptane/EtOAc as an eluent to give 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 (20.1 g, 76%): LC/MS (Table 2, Method g) Rt=1.76 min; MS m/z 616 (M+H)+.

Workup

  1. stirringthen stirred for about 10 min at rt
  2. temperatureThe mixture was cooled to about 0° C.
  3. stirringAfter stirring for about 10 min at about 0° C. the mixture
  4. temperatureto warm to rt
  5. concentrationAfter about 1 h the mixture was concentrated under reduced pressure
  6. customthen partitioned between EtOAc (300 mL) and water (200 mL)
  7. washThe organic layer was washed with saturated aqueous NaCl (100 mL)
  8. extractionthe combined aqueous layers were extracted with EtOAc (100 mL)
  9. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe material was purified on two successive 120 g silica columns with 8:2 heptane/EtOAc as an eluent

Sources & evidence

ORD record
ord-2d7fe3e1c3e948639aeb26fac0f9dc2b
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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