Piperazine → 5-(Piperazin-1-yl)isoquinoline

HRID 1371509Notes

Reaction equation

HRID 1371509 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[NH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.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]>[N:12]1([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]=[CH:7]3)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 4837PiperazineHCID 634876Binap, (A+-)-HCID 7364875-BromoisoquinolineHCID 23676156Sodium t-butoxide

Product 1

HCID 184141255-(Piperazin-1-yl)isoquinolineYield 63%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromoisoquinoline (250 mg, 1.2 mmol) is dissolved in toluene (5 mL). To the solution is added piperazine (258 mg, 3.0 mmol), Pd2dba3 (55 mg, 0.06 mmol), BINAP (112 mg, 0.18 mmol), and sodium t-butoxide (162 mg, 1.68 mmol). The mixture is degassed and then heated to 90° C. for about 12 hours. The reaction is allowed to cool to r.t., diluted with diethyl ether and filtered through celite. The filtrate is concentrated, and the dark residue is chromatographed on silica gel to give about 160 mg of 5-(piperazin-1-yl)isoquinoline (63%). EIS-MS: Found 214.0 (M+1).

Workup

  1. customThe mixture is degassed
  2. temperatureto cool to r.t.
  3. additiondiluted with diethyl ether
  4. filtrationfiltered through celite
  5. concentrationThe filtrate is concentrated
  6. customthe dark residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-7257c897616f4f16a397f33f5291d81e
Source dataset
uspto-grants-2007_01
Patent number
US07157463B2

Reaction notes

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