Acetic Acid → HCID 58382188, compound

HRID 1628035Notes

Reaction equation

HRID 1628035 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[CH:11]=[C:10]([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)[NH:9][C:5]2=[N:6][C:7]=1[CH3:8].C([Si](C)(C)C)#C.NC1C(Br)=NC(Br)=C(C)N=1.[OH-].[K+].[I:42]I.[H-].[Na+].[CH3:46][Si:47]([CH2:50][CH2:51][O:52][CH2:53]Cl)([CH3:49])[CH3:48].CC(O)=O>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]2[C:11]([I:42])=[C:10]([C:12]3[CH:13]=[CH:14][C:15]([C:18]4([CH3:23])[O:22][CH2:21][CH2:20][O:19]4)=[CH:16][CH:17]=3)[N:9]([CH2:53][O:52][CH2:51][CH2:50][Si:47]([CH3:49])([CH3:48])[CH3:46])[C:5]2=[N:6][C:7]=1[CH3:8]

Participants

10

Reactant 8

HCID 176Acetic AcidHCID 807IodineHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 66111TrimethylsilylacetyleneHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 217851463,5-Dibromo-6-methylpyrazin-2-amineHCID 58382269HCID 58382269, compound

Product 1

HCID 58382188HCID 58382188, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The 2-bromo-3-methyl-6-(4-(2-methyl-1,3-dioxolan-2-yl)phenyl)-5H-pyrrolo[2,3-b]pyrazine (10.4 g, 27.7 mmol, prepared using A from Preparation #4 with ethynyltrimethylsilane, Q, A with 2-amino-3,5-dibromo-6-methylpyrazine [WO2008/083070, Example 29, Part B] and B) in DMF (125 mL) was treated with KOH (1.87 g, 33.3 mmol) at rt. The mixture was stirred for about 10 min and iodine (7.74 g, 30.5 mmol) was added over about 15 min in two equal portions. The mixture was stirred for about 45 min then NaH (60 wt % in mineral oil, 1.33 g, 33.3 mmol) was added in portions over about 5 min. The mixture was stirred for about 10 min then SEMCl (5.17 mL, 29.1 mmol) was added. The mixture was stirred for about 30 min then the solvents were removed under reduced pressure. The material was partitioned between EtOAc (200 mL) and water (200 mL) containing AcOH (3.18 mL, 55.5 mmol). The layers were separated and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organics were washed with water (2×100 mL) then brine (100 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was dissolved purified with an 80 g silica gel column and eluted with 9:1 Heptane/EtOAc to give 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, 73%): LC/MS (Table 2, Method g) Rt=1.91 min; MS m/z 630 (M+H)+.

Workup

  1. stirringThe mixture was stirred for about 45 min
  2. stirringThe mixture was stirred for about 10 min
  3. stirringThe mixture was stirred for about 30 min
  4. customthe solvents were removed under reduced pressure
  5. customThe material was partitioned between EtOAc (200 mL) and water (200 mL)
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  8. washThe combined organics were washed with water (2×100 mL)
  9. dry with materialThe organic layer was dried over anhydrous MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe material was dissolved
  13. custompurified with an 80 g silica gel column
  14. washeluted with 9:1 Heptane/EtOAc

Sources & evidence

ORD record
ord-fb896b7f06e0478ca530baae9152e926
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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