tert-Butyl carbazate → HCID 58557307, compound

HRID 1969537Notes

Reaction equation

HRID 1969537 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Br[C:32]1[N:33]=[C:34]2[CH:40]=[C:39]([CH3:41])[N:38]([S:42]([C:45]3[CH:51]=[CH:50][C:48]([CH3:49])=[CH:47][CH:46]=3)(=[O:44])=[O:43])[C:35]2=[N:36][CH:37]=1.[NH:52]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[NH2:53].CC([O-])(C)C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:41][C:39]1[N:38]([S:42]([C:45]2[CH:51]=[CH:50][C:48]([CH3:49])=[CH:47][CH:46]=2)(=[O:44])=[O:43])[C:35]2=[N:36][CH:37]=[C:32]([NH:53][NH:52][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[N:33]=[C:34]2[CH:40]=1

Participants

7

Reactant 4

HCID 70091tert-Butyl carbazateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 58557085HCID 58557085, compound

Product 1

HCID 58557307HCID 58557307, compoundYield 14%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (0.250 g, 0.273 mmol) and 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (0.232 g, 0.546 mmol) were combined in 1,4-dioxane (15 mL). The flask was evacuated with some bubbling of solvent and then carefully refilled with nitrogen (3 times). Nitrogen was then bubbled directly into the reaction mixture. The mixture was then heated at about 80° C. for about 10 min and then removed from the heating source. 2-Bromo-6-methyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (1.0 g, 2.73 mmol), tert-butyl hydrazinecarboxylate (0.541 g, 4.10 mmol) and NaOt-Bu (0.501 mL, 4.10 mmol) were added and the reaction was heated at about 80° C. for about 1 h. The reaction was cooled to ambient temperature and the solvents removed under reduced pressure. The black residue was then taken up in EtOAc (50 mL) and filtered. The filtrate was washed with saturated aqueous NH4Cl (50 mL), EDTA (1.0 M aqueous, 50 mL) and saturated aqueous NaHCO3 (50 mL). The solution was dried over anhydrous Na2SO4, filtered, and concd under reduced pressure. The material was purified by chromatography on silica gel (80 g) eluting with 25-100% EtOAc in heptane to provide tert-butyl 2-(6-methyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarboxylate (0.160 g, 14%) as a brown oil: LCMS (Table 1, Method a) Rt=2.51 min; MS m/z: 418 (M+H)+.

Workup

  1. customThe flask was evacuated with
  2. customsome bubbling of solvent
  3. additioncarefully refilled with nitrogen (3 times)
  4. customNitrogen was then bubbled directly into the reaction mixture
  5. customremoved from the heating source
  6. temperaturethe reaction was heated at about 80° C. for about 1 h
  7. temperatureThe reaction was cooled to ambient temperature
  8. customthe solvents removed under reduced pressure
  9. filtrationfiltered
  10. washThe filtrate was washed with saturated aqueous NH4Cl (50 mL), EDTA (1.0 M aqueous, 50 mL) and saturated aqueous NaHCO3 (50 mL)
  11. dry with materialThe solution was dried over anhydrous Na2SO4
  12. filtrationfiltered
  13. customThe material was purified by chromatography on silica gel (80 g)
  14. washeluting with 25-100% EtOAc in heptane

Sources & evidence

ORD record
ord-25125604ecb84508b0d15d7b939eecd7
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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