(R)-tert-butyl 3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamothioyl)piperidine-1-carboxylate → (R)-tert-butyl 3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

HRID 1969782Notes

Reaction equation

HRID 1969782 reaction equation
[S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([CH2:20][NH:21][C:22]([C@@H:24]3[CH2:29][CH2:28][CH2:27][N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25]3)=S)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]>O1CCOCC1.FC(F)(F)C([O-])=O.[Hg+2].FC(F)(F)C([O-])=O>[S:1]([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:22]([C@@H:24]4[CH2:29][CH2:28][CH2:27][N:26]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25]4)=[N:21][CH:20]=3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]

Participants

4

Reactant 1

HCID 58557198(R)-tert-butyl 3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamothioyl)piperidine-1-carboxylate

Product 1

HCID 58557605(R)-tert-butyl 3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 2723924Mercury bis(trifluoroacetate)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-tert-butyl 3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamothioyl)-piperidine-1-carboxylate (5.61 g, 10.3 mmol) in 1,4-dioxane (96 mL) was added mercury (II) trifluoroacetate (4.38 g, 10.3 mmol). The reaction mixture was stirred at ambient temperature for about 2 h then filtered through a pad of Celite®. The Celite® pad was rinsed with EtOAc (50 mL) and the filtrate was concd under reduced pressure. The crude residue was dissolved in EtOAc (40 mL) and the organic phase was washed with saturated aqueous NaHCO3 (2×40 mL) and brine (30 mL), dried over anhydrous MgSO4, filtered, and coned under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to afford (R)-tert-butyl 3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (4.4 g, 87%): LC/MS (Table 1, Method b) Rt=2.49 min; MS m/z: 496 (M+H)+.

Workup

  1. filtrationthen filtered through a pad of Celite®
  2. washThe Celite® pad was rinsed with EtOAc (50 mL)
  3. dissolutionThe crude residue was dissolved in EtOAc (40 mL)
  4. washthe organic phase was washed with saturated aqueous NaHCO3 (2×40 mL) and brine (30 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. customThe crude material was purified by silica gel chromatography
  8. washeluting with a gradient of 0-5% MeOH in DCM

Sources & evidence

ORD record
ord-aaca21f669b0494ab5bbb28e421cad37
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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