tert-Butyl carbamate → 1,1-Dimethylethyl N-(5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazin-2-yl)carbamate

HRID 1854384Notes

Reaction equation

HRID 1854384 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]=[CH:39][N:38]([S:41]([C:44]3[CH:50]=[CH:49][C:47]([CH3:48])=[CH:46][CH:45]=3)(=[O:43])=[O:42])[C:35]2=[N:36][CH:37]=1.[C:51](=[O:58])([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[NH2:52].CC([O-])(C)C.[Na+]>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].O1CCOCC1>[S:41]([N:38]1[C:35]2=[N:36][CH:37]=[C:32]([NH:52][C:51](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])[N:33]=[C:34]2[CH:40]=[CH:39]1)([C:44]1[CH:50]=[CH:49][C:47]([CH3:48])=[CH:46][CH:45]=1)(=[O:43])=[O:42]

Participants

7

Reactant 4

HCID 77922tert-Butyl carbamateHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 23676156Sodium t-butoxideHCID 529876432-Bromo-5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazine

Product 1

HCID 580097831,1-Dimethylethyl N-(5-((4-methylphenyl)sulfonyl)-5H-pyrrolo(2,3-b)pyrazin-2-yl)carbamateYield 18.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a flask was added Pd2(dba)3 (1.3 g, 1.42 mmol), di-tert-butyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (1.21 g, 2.84 mmol), and 1,4-dioxane (75 mL). The catalyst-ligand mixture was degassed via vacuum/nitrogen purge (3 times) and heated at about 80° C. for about 10 min. Then 2-bromo-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (5.0 g, 14.2 mmol, Preparation #7), tert-butyl carbamate (2.5 g, 21.29 mmol), and NaOt-Bu (2.05 g, 21.29 mmol) were added. After an additional vacuum/nitrogen purge, the reaction was heated at about 80° C. for about 16 h. The reaction was cooled to ambient temperature and diluted with EtOAc (70 mL). The reaction mixture was filtered and the filtrate was washed with water (3×20 mL). The organic layer was dried over anhydrous MgSO4, filtered, and solvent removed under reduced pressure to give a reddish-brown solid. The crude material was purified via silica gel chromatography eluting with a gradient of 10-50% EtOAc in heptane to yield tert-butyl 5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-ylcarbamate as a yellow amorphous solid (1.0 g, 18%): LC/MS (Table 2, Method a) Rt=2.63 min; MS m/z: 389 (M+H)+.

Workup

  1. customThe catalyst-ligand mixture was degassed via vacuum/nitrogen
  2. custompurge (3 times)
  3. customAfter an additional vacuum/nitrogen purge
  4. temperaturethe reaction was heated at about 80° C. for about 16 h
  5. temperatureThe reaction was cooled to ambient temperature
  6. additiondiluted with EtOAc (70 mL)
  7. filtrationThe reaction mixture was filtered
  8. washthe filtrate was washed with water (3×20 mL)
  9. dry with materialThe organic layer was dried over anhydrous MgSO4
  10. filtrationfiltered
  11. customsolvent removed under reduced pressure
  12. customto give a reddish-brown solid
  13. customThe crude material was purified via silica gel chromatography
  14. washeluting with a gradient of 10-50% EtOAc in heptane

Sources & evidence

ORD record
ord-94be65a5da234fbfa39d9593ef17b2a4
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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