6-(Piperazin-1-yl)pyridine-3-carbonitrile → 6-[4-(1-Benzylisoquinolin-4-yl)piperazin-1-yl]nicotinonitrile

HRID 42219

Reaction equation

HRID 42219 reaction equation
[CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](Br)=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:19]1([C:25]2[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][N:26]=2)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.CC(C)([O-])C.[Na+]>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].O1CCOCC1>[CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([N:22]2[CH2:23][CH2:24][N:19]([C:25]3[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][N:26]=3)[CH2:20][CH2:21]2)=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 27371846-(Piperazin-1-yl)pyridine-3-carbonitrileHCID 236284181-Benzyl-4-bromoisoquinolineHCID 23676156Sodium t-butoxide

Product 1

HCID 250663226-[4-(1-Benzylisoquinolin-4-yl)piperazin-1-yl]nicotinonitrileYield 25%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 40 mL vial 120 mg (0.40 mmol) 1-benzyl-4-bromo-isoquinoline (see above), 160 mg (0.84 mmol) 6-piperazin-1-yl-nicotinonitrile, 40 mg (0.04 mmol) tris(dibenzylideneaceton)dipalladium(0), and 60 mg (±)-(1,1′-binaphthalene-2-2′diyl)bis(diphenylphosphine) are added to 5 mL dioxane. After flushing the vial with nitrogen for 5 min, the reaction mixture is stirred for 2 min followed by the addition of 150 mg (1.55 mmol) sodium tert-butoxide. After flushing with nitrogen for 5 min, the vial is sealed and heated at 80° C. for 12 h. After cooling, the mixture is loaded onto a silica column directly and purified. The eluent containing the correct mass is concentrated in vacuo and the resulting residue is purified by reversed phase HPLC using a Varian Prostar system equipped with a Waters xTerra column (50×100 mm) and a solvent gradient of 0.1% NH3 in water/0.1% NH3 in acetonitrile (0→100%). Pure fractions are pooled and evaporated to give 40 mg (0.10 mmol, 25% yield) of the title compound.

Workup

  1. customAfter flushing the vial with nitrogen for 5 min
  2. customAfter flushing with nitrogen for 5 min
  3. customthe vial is sealed
  4. temperatureAfter cooling
  5. custompurified
  6. additionThe eluent containing the correct mass
  7. concentrationis concentrated in vacuo
  8. customthe resulting residue is purified by reversed phase HPLC
  9. customequipped with a Waters xTerra column (50×100 mm)
  10. customevaporated

Sources & evidence

ORD record
ord-d0f04cd803e144d090b52d5afa8a6e4a
Source dataset
uspto-grants-2013_09
Patent number
US08536168B2

Linked notes

Loading…