Cis-2-boc-hexahydropyrrolo[3,4-C]pyrrole → HCID 44469278, compound

HRID 1254814Notes

Reaction equation

HRID 1254814 reaction equation
CC(C)([O-])C.[Na+].[CH2:7]1[C@@H:11]2[CH2:12][NH:13][CH2:14][C@@H:10]2[CH2:9][N:8]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].Br[C:23]1[CH:32]=[C:31]2[C:26]([C:27]([NH:33][C:34]([NH:36][C:37]3[CH:42]=[N:41][CH:40]=[CH:39][N:38]=3)=[O:35])=[CH:28][CH:29]=[N:30]2)=[CH:25][CH:24]=1>C1COCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].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]>[N:38]1[CH:39]=[CH:40][N:41]=[CH:42][C:37]=1[NH:36][C:34](=[O:35])[NH:33][C:27]1[C:26]2[C:31](=[CH:32][C:23]([N:13]3[CH2:12][C@@H:11]4[CH2:7][N:8]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:9][C@@H:10]4[CH2:14]3)=[CH:24][CH:25]=2)[N:30]=[CH:29][CH:28]=1

Participants

7

Reactant 3

HCID 1514452Cis-2-boc-hexahydropyrrolo[3,4-C]pyrroleHCID 23676156Sodium t-butoxideHCID 24859298HCID 24859298, compound

Product 1

HCID 44469278HCID 44469278, compoundYield 91.8%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of sodium tert-butoxide (98 mg, 1.017 mmol) and (3aR,6aS)-tert-butyl hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (95 mg, 0.436 mmol) in THF (3 mL) was stirred under nitrogen. To this was added 1,1′-bis(diphenylphosphino)ferrocene (25 mg, 0.05 mmol), Pd2(DBA)3 (12 mg, 0.02 mmol) and 1-(7-bromoquinolin-4-yl)-3-(pyrazin-2-yl)urea (100 mg, 0.291 mmol). The mixture was then heated at reflux for 12 h before partitioning between CH2Cl2 and water. The mixture was filtered through Celite and the organic phase was separated. The water phase was extracted twice with CH2Cl2 and the combined extracts dried (Na2SO4), filtered and concentrated in vacuo to provide the crude material, which was purified by flash chromatography to give the title compound (127 mg, 83%) as a white solid.

Workup

  1. temperatureThe mixture was then heated
  2. temperatureat reflux for 12 h
  3. custombefore partitioning between CH2Cl2 and water
  4. filtrationThe mixture was filtered through Celite
  5. customthe organic phase was separated
  6. extractionThe water phase was extracted twice with CH2Cl2
  7. dry with materialthe combined extracts dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto provide the crude material, which
  11. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-1b403cbccfa1431893853dbaf995af40
Source dataset
uspto-grants-2013_06
Patent number
US08455648B2

Reaction notes

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