1-[(6-Chloropyridin-3-yl)methyl]-4-methylpiperazine → 5-((4-Methylpiperazin-1-yl)methyl)pyridin-2-amine

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Reaction Conditions

Reaction Steps

To 1-((6-chloropyridin-3-yl)methyl)-4-methylpiperazine (6.79 g, 30.1 mmol, Eq: 1.00), 2-(dicyclohexylphosphino)biphenyl (2.11 g, 6.02 mmol, Eq: 0.20) and tris(dibenzylideneacetone)dipalladium (0) (2.75 g, 3.01 mmol, Eq: 0.10) in a sealed tube was added THF (75 ml). The solution was placed under nitrogen. Lithium bis(trimethylsilyl)amide (75.2 ml, 75.2 mmol, Eq: 2.50) was added. The solution was degassed with argon and the tube was sealed and heated at 100° C. for 18 h. The solution was filtered through Celite™. The solvent was evaporated under reduced pressure. The residue was taken up in DCM. HCl (1N, 10 ml) was added slowly to adjust to pH=1 by adding 6 N HCl and water (as needed). The layers were separated. The organic layer was extracted once with water. The aqueous layers were combined and were brought to pH 10 by a slow addition of solid NaOH. Dichloromethane was added. The layers were separated. The aqueous layer was extracted three times with DCM. The organic layers were combined and dried over Na2SO4. The solvent was evaporated. The residue was triturated with Et2O. The solid was collected by filtration and dried to give 5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamine (2.3 g, 37%). LC/MS-ESI observed [M+H]+ 207.

Provenance & Evidence