Process for preparing substituted benzo[1,2-G]-chrome-3-ene, benzo[1,2-G]-thiochrom-3-ene and benzo[1,2-G]-1,2-dihydroquinoline derivatives

A process for preparing a compound of formula (1)

• 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 (R4)s-heteroaryl where heteroaryl is selected from the group consisting of pyridyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, imidazolyl and pyrrazolyl;
• R1 is lower alkyl of 1 to 6 carbons;
• R2 and R4 are alkyl of 1 to 6 carbons, F, Cl, Br, I, NO2, N3, (CH2)pCOOH, (CH2)pCOOR1;
• 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 R2 groups, or Y is —(CR3═CR3)2—;
• R3 is H or lower alkyl of 1 to 6 carbons;
• A is (CH2)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 —(CR3═CR3)2— then A is (CH2)q and q is 0;
• B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR8, CONR9R10, —CH2OH, CH2OR11, CH2OCOR11, CHO, CH(OR12)2, CHOR13O, —COR7, CR7(OR12)2, CR7OR13O, or Si(C1-6alkyl)3, where R7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R8 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 R8 is phenyl or lower alkylphenyl, R9 and R10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R11 is lower alkyl, phenyl or lower alkylphenyl, R12 is lower alkyl, and R13 is divalent alkyl radical of 2-5 carbons,
• the process comprising the steps of:
• reacting a compound of formula (2)
• where X1 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 X1, and to provide an intermediate tertiary alcohol;
• dehydrating the intermediate tertiary alcohol to provide a compound of formula (3), and
• providing a reagent of the formula X3—Y(R2)—A—B where X3 is halogen, converting one of the compounds selected from the group consisting of the compound of formula (3) and a compound of the formula X3—Y(R2)—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 CHR3═CR3—CR3═CR3—B in the presence of a catalyst, to provide the compound of formula (1).