Ethyl Acetate → tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate

HRID 2204512Notes

Reaction equation

HRID 2204512 reaction equation
[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH:3]1[C:15](=O)[NH:16][CH2:17][C:18]1[N:19]=[C:20]2[CH:26]=[CH:25][N:24]([S:27]([C:30]3[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[C:21]2=[N:22][CH:23]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1.CCOC(C)=O>O1CCOCC1.C(O[Hg]OC(=O)C)(=O)C>[CH3:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:12])[CH3:13])=[O:9])[CH2:4][CH:3]1[C:15]1[N:19]2[C:20]3[CH:26]=[CH:25][N:24]([S:27]([C:30]4[CH:31]=[CH:32][C:33]([CH3:34])=[CH:35][CH:36]=4)(=[O:28])=[O:29])[C:21]=3[N:22]=[CH:23][C:18]2=[CH:17][N:16]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 87949Lawesson's reagentHCID 58009799tert-butyl 4-methyl-3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate

Product 1

HCID 58009941tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylateYield 44.9%

Reagents, catalysts & solvents 2

HCID 16683746DiacetyloxymercuryCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl 4-methyl-3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate (44 g, 83 mmol, Example #13, Step H) in 1,4-dioxane (500 mL) was added Lawesson's reagent (20.2 g, 50.0 mmol). The reaction was heated at about 80° C. for about 1 h. The reaction was allowed to cool to ambient temperature followed by the addition of diacetoxymercury (26.6 g, 83.0 mmol). After about 1 h, additional diacetoxymercury (13.3 g, 42.0 mmol) was added. After about 15 min, the reaction was poured into stirred EtOAc (2 L). After about 15 min the reaction was filtered through Celite® and the filtrate was concentrated under reduced pressure. The resulting residue was triturated with EtOAc (500 mL) and filtered. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography (330 g column) eluting with a gradient of 10-50% EtOAc in heptane to provide tert-butyl 4-methyl-3-(6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)piperidine-1-carboxylate (19 g, 44%) as a white solid: LC/MS (Table 2, Method a) Rt=2.57 min; MS m/z: 510 (M+H)+.

Workup

  1. temperatureto cool to ambient temperature
  2. waitAfter about 15 min
  3. additionthe reaction was poured
  4. filtrationAfter about 15 min the reaction was filtered through Celite®
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe resulting residue was triturated with EtOAc (500 mL)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. custompurified by silica gel chromatography (330 g column)
  10. washeluting with a gradient of 10-50% EtOAc in heptane

Sources & evidence

ORD record
ord-78c2bfd5806c460e8441775bacd67fbc
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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