1-(But-3-yn-1-yl)piperidine → 2-(4-Piperidin-1-yl-but-1-ynyl)-5-piperidin-1-ylmethyl-pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of trifluoro-methanesulfonic acid 5-piperidin-1-ylmethyl-pyridin-2-yl ester (0.10 g, 0.31 mmol), 1-but-3-ynyl-piperidine (0.051 g, 0.37 mmol), and TEA (2 mL) in dry DMF (1 mL) was added dichlorobis(triphenylphosphine)-palladium(II) (0.004 g, 0.006 mmol) and copper(I) iodide (0.004 g, 0.016 mmol). The reaction mixture was heated at 80° C. for 4 h, cooled to rt, diluted with DCM (25 mL), and filtered through a pad of diatomaceous earth. The mixture was diluted with 1 N NaOH (25 mL) and extracted with DCM (3×25 mL). The organic layers were combined, dried (Na2SO4), and concentrated, and chromatography of the resulting residue (SiO2: 3-6% 2 M NH3 in MeOH/DCM) gave the title compound (0.01 g, 10%). MS (ESI): exact mass calcd. for C20H29N3, 311.2; m/z found, 312.5 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.45 (d, J=2.0, 1H), 7.62 (d, J =8.3, 1H), 7.25 (d, J=8.1, 1H), 3.47 (s, 2H), 2.74-2.70 (m, 4H), 2.62-2.59 (m, 4H), 2.37 (br s, 4H), 1.65-1.55 (m, 8H), 1.46-1.44 (m, 4H).

Provenance & Evidence