Patent ID: 6037470
Filing Date: 2000-03-14
Classification: A61P,C07D

Abstract:
A method of forming a compound having the formula (I): ##STR19## wherein: Z is selected from the group consisting of CH.sub.2, CH.sub.2 CH.sub.2, CH(CH.sub.3), CH.dbd.CH, C.tbd.C, NH, N(C.sub.1 -C.sub.3 alkyl), O, S, C(O)CH.sub.2 and OCH.sub.2 ;R.sup.1 and R.sup.2 are independently selected from the group consisting of hydrogen and a C.sub.1 -C.sub.8 straight or branched alkyl or a C.sub.3 -C.sub.8 cycloalkyl;R.sup.3 is a C.sub.1 -C.sub.12 straight or branched alkyl;R.sup.4 is a C.sub.3 -C.sub.10 cycloalkyl optionally substituted with OH, or a C.sub.3 -C.sub.10 cycloalkenyl optionally substituted with OH; andR.sup.8 is a C.sub.1 -C.sub.8 straight or branched alkyl or a C.sub.3 -C.sub.8 cycloalkyl, optionally substituted with OH;said method comprising the steps of;(a) reacting a compound of the formula (II) ##STR20## wherein Z, R.sup.3 and R.sup.4 are as defined above, with an effective amount of ethyl cyanoacetate to form a compound of the formula (III) ##STR21## wherein Z, R.sup.3 and R.sup.4 are as defined above; (b) subjecting said compound (III) to successive steps of nitrosating with a nitrosating agent to form a nitro group, reduction of the nitro group to an amine group with a reducing agent, and acylation of the amine group to an amide group with an acylating agent, to form compound (IV) ##STR22## wherein Z, R.sup.3, R.sup.4 and R.sup.8 are as defined above; (c) reacting said compound (IV) with an effective amount of a base to form compound (V) ##STR23## wherein Z, R.sup.3, R.sup.4 and R.sup.8 are as defined above; (d) reacting said compound (V) with an effective amount of a desulfurization compound to form compound (VI) ##STR24## wherein Z, R.sup.3, R.sup.4 and R.sup.8 are as defined above; and (e) subjecting said oxo group of compound (VI) to the successive steps of halogenation with a halogenating agent and displacement with an amine of the formula NR.sup.1 R.sup.2, wherein R.sup.1 and R.sup.2 are as defined above, to form said compound of formula 1.