Diethyl Ether → (4-Isopropyl-piperazin-1-yl)-(6-piperidin-1-ylmethyl-pyridin-3-yl)-methanone

Participants

Reaction Steps

A solution of 6-piperidin-1-ylmethyl-nicotinic acid methyl ester (0.300 g, 1.28 mmol), and MgBr2.OEt2 (0.900 g, 3.84 mmol) in THF (15 mL) was stirred for 15 min. A solution of 1-isopropyl-piperazine (0.325 g, 2.56 mmol) in THF (2 mL) was then added to the reaction drop-wise and the mixture was heated at reflux for 48 h. The reaction mixture was cooled to rt, concentrated, treated with 1 N aq. NaHCO3 (50 mL), and extracted with ethyl acetate (3×50 mL). The organic layers were combined, dried (Na2SO4), and concentrated. Chromatography of the residue (SiO2; 3-6% 2 M NH3 in MeOH/DCM) gave the title compound as an oil (0.297 g, 70%). MS (ESI): exact mass calcd. for C19H30N4O, 330.2; m/z found, 331.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.55 (d, J=2.2, 1H), 7.87 (dd, J=7.8, 2.0, 1H), 7.62 (d, J=7.6, 1H), 3.78 (br s, 2H), 3.67 (s, 2H), 3.48 (br s, 2H), 2.77-2.73 (m, 1H), 2.65-2.48 (m, 8H), 1.65-1.59 (m, 4H), 1.49-1.48 (m, 2H), 1.09 (d, J=6.6, 6H).

Provenance & Evidence