N,N'-Dimethylethylenediamine → tert-butyl N-[(3S)-1-[3-methoxy-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate

HRID 57895Notes

Reaction equation

HRID 57895 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[N:13]=[CH:12][C:11]3[CH:14]=[N:15][NH:16][C:10]=3[CH:9]=2)[CH:5]=[N:4][CH:3]=1.Br[C:18]1[N:23]=[C:22]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25]2)[C:21]([O:38][CH3:39])=[CH:20][CH:19]=1.CNCCNC.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Cu](I)I>[CH3:39][O:38][C:21]1[C:22]([N:24]2[CH2:29][CH2:28][CH2:27][C@H:26]([NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[CH2:25]2)=[N:23][C:18]([N:16]2[C:10]3[CH:9]=[C:8]([C:6]4[CH:5]=[N:4][CH:3]=[C:2]([CH3:1])[N:7]=4)[N:13]=[CH:12][C:11]=3[CH:14]=[N:15]2)=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 867070806-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridineHCID 86707086tert-butyl N-[(3S)-1-(6-bromo-3-methoxy-2-pyridyl)-3-piperidyl]carbamate

Product 1

HCID 86707087tert-butyl N-[(3S)-1-[3-methoxy-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamateYield 58.3%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine (0.4734 mmol; 100.0 mg), tert-butyl N-[(3S)-1-(6-bromo-3-methoxy-2-pyridyl)-3-piperidyl]carbamate (0.5681 mmol, 219.5 mg), N,N′-Dimethylethylenediamine (0.4734 mmol; 41.73 mg; 0.0471 mL), copper iodide (0.4734 mmol; 91.08 mg), and potassium carbonate (0.5208 mmol; 72.70 mg) in 1,4-Dioxane (10 mL) was purged with Argon, then sealed and stirred at 100° C. overnight. The mixture was cooled to room temperature, and then filtered through Celite. The filtrate was concentrated; the residue was purified on silica eluted with 0 to 100% EtOAc in DCM to afford tert-butyl N-[(3S)-1-[3-methoxy-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-3-piperidyl]carbamate as a tan solid (142.5 mg, 58%).

Workup

  1. customwas purged with Argon
  2. customsealed
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through Celite
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified on silica
  7. washeluted with 0 to 100% EtOAc in DCM

Sources & evidence

ORD record
ord-5391cd1c9a1b47f2a558cb72146f6c8a
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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