Tetrahydrofuran → Tert-butyl 3-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-4-oxo-piperidine-1-carboxylate

HRID 57975Notes

Reaction equation

HRID 57975 reaction equation
Br[C:2]1[N:7]=[C:6]([N:8]2[C:16]3[CH:15]=[C:14]([C:17]4[CH:22]=[N:21][CH:20]=[C:19]([CH3:23])[N:18]=4)[N:13]=[CH:12][C:11]=3[CH:10]=[N:9]2)[CH:5]=[CH:4][CH:3]=1.[O:24]=[C:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1.CC(C)([O-])C.[Na+].O1CCCC1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:23][C:19]1[N:18]=[C:17]([C:14]2[N:13]=[CH:12][C:11]3[CH:10]=[N:9][N:8]([C:6]4[N:7]=[C:2]([CH:30]5[C:25](=[O:24])[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:29]5)[CH:3]=[CH:4][CH:5]=4)[C:16]=3[CH:15]=2)[CH:22]=[N:21][CH:20]=1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 867071541-(6-Bromo-2-pyridyl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine

Product 1

HCID 86707157Tert-butyl 3-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-4-oxo-piperidine-1-carboxylateYield 60.6%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
48 °C

Procedure

To a solution of 1-(6-bromo-2-pyridyl)-6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridine (125 mg, 0.340 mmol), tert-butyl 4-oxopiperidine-1-carboxylate (100 mg, 0.51 mmol), palladium acetate (8.0 mg, 0.034 mmol) and sodium tert-butoxide (74 mg, 0.75 mmol) in tetrahydrofuran (8.0 ml, 99 mmol) was added tri-t-butylphosphine (0.020 mL, 0.068 mmol). The mixture was degassed and heat at 48° C. 2 h. The reaction was quenched with water then extract with EtOAc. The organic layers was dried with sodium sulfate, filtered, and concentrated in vacuum. The crude product was purified by flash chromatography (EtOAc/Heptane eluted @75% EtOAc) to give the desired product 100 mg 60% yield. MS (ESI) m/z: 486.1.

Workup

  1. customThe mixture was degassed
  2. custom2 h
  3. customThe reaction was quenched with water
  4. extractionthen extract with EtOAc
  5. dry with materialThe organic layers was dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuum
  8. customThe crude product was purified by flash chromatography (EtOAc/Heptane eluted @75% EtOAc)

Sources & evidence

ORD record
ord-c1c9d3e71f34477c813ea2196b6801c1
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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