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

HRID 449651Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C[Si]([N-:45][Si](C)(C)C)(C)C.[Li+]>C1COCC1.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]>[CH3:15][N:12]1[CH2:13][CH2:14][N:9]([CH2:8][C:5]2[CH:4]=[CH:3][C:2]([NH2:45])=[N:7][CH:6]=2)[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a sealed tube under nitrogen was added 1-((6-chloropyridin-3-ylmethyl)-4-methylpiperazine (13.5 g, 59.8 mmol, Eq:1.00), 2-(dicyclohexylphosphino)biphenyl (4.19 g, 12.0 mmol, Eq:0.20), tris(dibenzylideneacetone)-dipalladium (0) (5.48 g, 5.98 mmol, Eq: 0.10), and lithium bis(trimethylsilyl)amide, 150 ml of a 1.0M solution in THF. An additional 150 ml THF was added. The flask was degassed with argon. The flask was capped and the reaction heated at 100° C. overnight. 3M HCl was added along with DCM to the material and the layers were separated. The aqueous layer was bacidified with 3M NaOH. The aqueous layer was then extracted 3 times with DCM to provide 3.2 g (25.9%) of a yellow powder which was used without further purification.

Workup

customThe flask was degassed with argon
customThe flask was capped
addition3M HCl was added along with DCM to the material
customthe layers were separated
extractionThe aqueous layer was then extracted 3 times with DCM

Sources & evidence

ORD record: ord-a1c7c3ab071e46c8bba870d113e02814
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481540B2

Reaction notes

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