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

HRID 57924Notes

Reaction equation

HRID 57924 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.Cl[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)[C:21]([CH3:39])=[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]>[CH3:39][C:21]1[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]([CH3:36])([CH3:35])[CH3:37])[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 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 86707113tert-butyl N-[(3S)-1-(6-chloro-3-methyl-2-pyridyl)-6-oxo-3-piperidyl]carbamate

Product 1

HCID 86707114tert-butyl N-[(3S)-1-[3-methyl-6-[6-(6-methylpyrazin-2-yl)pyrazolo[4,3-c]pyridin-1-yl]-2-pyridyl]-6-oxo-3-piperidyl]carbamateYield 20.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-(6-methylpyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridine (150 mg, 0.710 mmol), tert-butyl N-[(3S)-1-(6-chloro-3-methyl-2-pyridyl)-6-oxo-3-piperidyl]carbamate (497 mg, 1.42 mmol), tris(dibenzylideneacetone)dipalladium(0) (65 mg, 0.071 mmol), xantphos (84 mg, 0.14 mmol), and sodium tert-butoxide (140 mg, 1.42 mmol) in toluene 3.0 mL was stirred at 110° C. 18 h. The reaction was filtered through celite. The crude product was purified by flash chromatography (EtOAc/Heptane then MeOH/DCM eluted at 10% MeOH) to give the desired product 75 mg 20% yield. MS (ESI) m/z: 515.1.

Workup

  1. custom18 h
  2. filtrationThe reaction was filtered through celite
  3. customThe crude product was purified by flash chromatography (EtOAc/Heptane
  4. washMeOH/DCM eluted at 10% MeOH)

Sources & evidence

ORD record
ord-ab136a8b0c7f4e91a4f42817369e7c8a
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

Loading…