New and efficient technique for the synthesis of Urapidil using β-cyclodextrin as an inverse phase-transfer catalyst

摘要

A novel and efficient procedure has been developed for the preparation of Urapidil, (6-({3-4-(2-methoxyphenyl) piperazin-1-yl] propyl} amino)-1,3-dimethyl pyrimidine-2,4-(1H, 3H)-dione), from 6-[(3-chloropropyl) amino]-l, 3-dimethyluracil and l-(2-methoxyphenyl) piperazine hydrochloride under inverse phase-transfer catalysis (IPTC) conditions. To optimize the reaction conditions, the alkyla-tion reaction was carried out with a range of inverse phase-transfer catalysts, agitation speeds, reaction times, reaction temperatures, mole ratios and catalyst loadings. In addition, the factors affecting the rate of reaction were studied and the rate constant obtained is consistent with the pseudo-first order rate equation. When β-cyciodextrin was used as a catalyst, Urapidil was obtained as a white crystalline powder in 82.6% isolated yield with 99.6% purity after 2-3 h reaction in alkaline aqueous media at 95 °C with an agitation rate of 1500 rpm.