Cipamfylline, HEP-688, BRL-61063

西潘茶碱Chemical Name: 8-Amino-1,3-bis(cyclopropylmethyl)xanthine
CAS No. 132210-43-6
项目整合开发状态: Phase II
项目研究机构: GlaxoSmithKline (Originator), Leo (Licensee)
合成路线:N,N'-Bis(cyclopropylmethyl)urea (II) was prepared by the action of phosgene on cyclopropylmethylamine (I).Cyclization of urea (II) with cyanoacetic acid (III) in hot acetic anhydride produced the 6-aminouracil (IV).Subsequent nitrosation of (IV) by means of sodium nitrite and formic acid afforded the 5-nitroso derivative (V),which was further reduced to the 5,6-diaminouracil (VI) with sodium dithionite.Formylation of diamine (VI),followed by cyclization of the intermediate formamide (VII),gave rise to 1,3-bis(cyclopropylmethyl)xanthine (VIII).Nitration of xanthine (VIII) with HNO3 in acetic acid yielded the 8-nitro derivative (IX),which was finally reduced to the corresponding amine employing either tin and HCl or sodium dithionite.