1-Methylpiperazine → 1-Ethyl-6-(4-methylpiperazin-1-yl)indole-3-carbonitrile

HRID 502252Notes

Reaction equation

HRID 502252 reaction equation
Cl[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:13]#[N:14])=[CH:7][N:8]2[CH2:11][CH3:12])=[CH:4][CH:3]=1.ClC1C=C2C(C=CN2)=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[CH3:58][N:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]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].ClCCl.COCCOC>[CH2:11]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([N:62]3[CH2:63][CH2:64][N:59]([CH3:58])[CH2:60][CH2:61]3)[CH:10]=2)[C:6]([C:13]#[N:14])=[CH:7]1)[CH3:12]

Participants

9

Reactant 5

HCID 531671-MethylpiperazineHCID 62657Potassium Phosphate, TribasicHCID 871116-ChloroindoleHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 594261566-Chloro-1-ethylindole-3-carbonitrile

Product 1

HCID 594264431-Ethyl-6-(4-methylpiperazin-1-yl)indole-3-carbonitrileYield 72%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

6-chloro-1-ethylindole-3-carbonitrile (1.02 g, 5.0 mmol), prepared from 6-chloroindole using the procedures described in example 1A, is mixed with K3PO4 (1.48 g, 7.0 mmol), Pd2(dba)3 (0.11 g, 0.12 mmol), biphenyl-2-yldicyclohexylphosphane (0.17 g, 0.48 mmol), 1-methylpiperazine (0.60 g, 0.67 mL 6.0 mmol) and dry DME (10.0 mL). The mixture is stirred at 100° C. overnight. After cooling, the solvent is replaced with dichloromethane and chromatographed (silica gel, DCM, then EtOAc, finally DCM/MeOH, 9/1) to provide 1-ethyl-6-(4-methylpiperazin-1-yl)indole-3-carbonitrile (0.96 g, 72%).

Workup

  1. temperatureAfter cooling
  2. customchromatographed (silica gel, DCM

Sources & evidence

ORD record
ord-f62441dae984499981f37804256363fb
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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