1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → tert-butyl N-[(3S)-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-6-oxo-3-piperidyl]carbamate

HRID 57904Notes

Reaction equation

HRID 57904 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[C:29](=[O:30])[CH2:28][CH2:27][C@H:26]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:25]2)[CH:21]=[CH:20][CH:19]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][C:2]1[N:7]=[C:6]([C:8]2[N:13]=[CH:12][C:11]3[CH:14]=[N:15][N:16]([C:18]4[N:23]=[C:22]([N:24]5[C:29](=[O:30])[CH2:28][CH2:27][C@H:26]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:36])([CH3:35])[CH3:37])[CH2:25]5)[CH:21]=[CH:20][CH:19]=4)[C:10]=3[CH:9]=2)[CH:5]=[N:4][CH:3]=1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 867070806-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridineHCID 86707098tert-butyl N-[(3S)-1-(6-bromo-2-pyridyl)-6-oxo-3-piperidyl]carbamate

Product 1

HCID 86707097tert-butyl N-[(3S)-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-6-oxo-3-piperidyl]carbamateYield 28%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine (75 mg, 0.36 mmol), tert-butyl N-[(3S)-1-(6-bromo-2-pyridyl)-6-oxo-3-piperidyl]carbamate (158 mg, 0.426 mmol), tris(dibenzylideneacetone)dipalladium(0) (32 mg, 0.036 mmol), xantphos (42 mg, 0.071 mmol), and sodium tert-butoxide (70 mg, 0.71 mmol) in toluene 6.0 mL was stirred at 100° C. 18 h. The reaction was filtered through celite. The crude product was purified by flash chromatography (EtOAc/Heptane eluted at 100% EtOAc) to give tert-butyl N-[(3S)-1-[6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-6-oxo-3-piperidyl]carbamate (50 mg) in 28% yield.

Workup

  1. custom18 h
  2. filtrationThe reaction was filtered through celite
  3. customThe crude product was purified by flash chromatography (EtOAc/Heptane eluted at 100% EtOAc)

Sources & evidence

ORD record
ord-c9181c58670447f2ae7a117328be304f
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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