Hydrochloric Acid → (S)-1-Isopropyl-4-[1-(6-cyanopyridin-3-yl)-piperidine-4-carbonyl]-2-methyl piperazine hydrochloride

Participants

Reaction Steps

(S)-1-Isopropyl-4-(piperidine-4-carbonyl)-2-methylpiperazine dihydrochloride (D29) (0.2 g), 2-cyano-5-bromopyridine (0.14 g) and potassium carbonate (0.22 g) were stirred in DMSO (4 ml) at 120° C. for 2 h. After cooling, the potassium carbonate was filtered off and the DMSO filtrate was diluted with MeOH (20 ml). The crude mixture was poured onto a 10 g isolute SCX column which was washed first with MeOH (50 ml) and then eluted with 10% ammonia in MeOH (50 ml). The product was further purified by column chromatography (silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]. Fractions containing the required product were evaporated to give the free base which was dissolved in DCM (10 ml) and treated with 1N HCl in diethyl ether to give the title compound (E78) as a light yellow solid (30 mg). LCMS electrospray (+ve) 356.(MH+). 1H NMR [DMSO-d6]δ: 1.09 (3H, d, J=6.4 Hz), 1.33-1.35 (6H, d, J=6.5 Hz), 1.54-1.74 (4H, m), 2.98-3.16 (5H, m), 3.23-3.68 (3H, m), 3.83-4.45 (5H, m), 7.37 (1H, dd, J=8.8 Hz), 7.72 (1H, d, J=8.8 Hz), 8.4(1H, d, J=2.8 Hz), 10.9 (1H, bs)

Provenance & Evidence