Patent ID: 6211385
Filing Date: 2001-04-03
Classification: C07D

Abstract:
A process for preparing a compound of formula (1) ##STR9##where X is S;R is alkyl of 1 to 10 carbons, alkenyl of 1 to 10 carbons and of 1 to 3 double bonds, alkynyl of 1 to 10 carbons and of 1 to 3 triple bonds, aryl or (R.sub.4).sub.s -heteroaryl where heteroaryl is selected from the group consisting of pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl and pyrrazolyl;R.sub.1 is lower alkyl of 1 to 6 carbons;R.sub.2 and R.sub.4 are alkyl of 1 to 6 carbons, F, Cl, Br, I, NO.sub.2, N.sub.3, (CH.sub.2).sub.p COOH, (CH.sub.2).sub.p COOR.sub.1 ;o, p and s are integers each independently having the value of 0 to 2;Y is a phenyl or naphthyl group, or heteroaryl selected from a group consisting of pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl and pyrrazolyl, said phenyl and heteroaryl groups being optionally substituted with one or two R.sub.2 groups, or Y is --(CR.sub.3.dbd.CR.sub.3).sub.2 --;R.sub.3 is H or lower alkyl of 1 to 6 carbons;A is (CH.sub.2).sub.q where q is 0-5, lower branched chain alkyl having 3-6 carbons, cycloalkyl having 3-6 carbons, alkenyl having 2-6 carbons and 1 or 2 double bonds, alkynyl having 2-6 carbons and 1 or 2 triple bonds, with the proviso that when Y is --(CR.sub.3.dbd.CR.sub.3).sub.2 -- then A is (CH.sub.2).sub.q and q is 0;B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR.sub.8, CONR.sub.9 R.sub.10, --CH.sub.2 OH, CH.sub.2 OR.sub.11, CH.sub.2 OCOR.sub.11, CHO, CH(OR.sub.12).sub.2, CHOR.sub.13 O, --COR.sub.7, CR.sub.7 (OR.sub.12).sub.2, CR.sub.7 OR.sub.13 O, or Si(C.sub.1-6 alkyl).sub.3, where R.sub.7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R.sub.8 is an alkyl group of 1 to 10 carbons or (trimethylsilyl)alkyl where the alkyl group has 1 to 10 carbons, or a cycloalkyl group of 5 to 10 carbons, or R.sub.8 is phenyl or lower alkylphenyl, R.sub.9 and R.sub.10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R.sub.11 is lower alkyl, phenyl or lower alkylphenyl, R.sub.12 is lower alkyl, and R.sub.13 is divalent alkyl radical of 2-5 carbons,the process comprising the steps of:reacting a compound of formula (2) ##STR10##where X.sub.1 is halogen with an organometal reagent of the formula R--M where M is a monovalent, divalent or trivalent metal, to selectively react with the endocyclic ketone function of the compound of formula (2) in preference over the halogen X.sub.1, and to provide an intermediate tertiary alcohol;dehydrating the intermediate tertiary alcohol to provide a compound of formula (3), and ##STR11##providing a reagent of the formula X.sub.3 --Y(R.sub.2)--A--B where X.sub.3 is halogen, converting one of the compounds selected from the group consisting of the compound of formula (3) and a compound of the formula X.sub.3 --Y(R.sub.2)--A--B into an organometal reagent, and reacting the organometal reagent with the other compound of said group, or reacting the compound of formula (3) with a reagent of the formula CHR.sub.3.dbd.CR.sub.3 --CR.sub.3.dbd.CR.sub.3 --B in the presence of a catalyst, to provide the compound of formula (1).