Process for the preparation of 2,2'-bipyrrolyl-pyrromethene (prodigiosins) derivatives

A process for the preparation of a 5-›(2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole compound of formula (I):

• ##STR11## wherein R1 represents hydrogen, phenyl, C.sub.1 -C.sub.20 alkyl or C.sub.2 -C.sub.20 alkenyl, wherein the alkyl and alkenyl groups are unsubstituted or substituted by 1 to 3 substituents chosen independently from halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, aryl and aryloxy;
• R2 represents hydrogen, C.sub.1 -C.sub.6 alkyl, cyano, carboxy or (C.sub.1 -C.sub.6 alkoxy)carbonyl;
• R3 represents halogen, hydroxy or C.sub.1 -C.sub.11 alkoxy unsubstituted or substituted by phenyl;
• R4 represent hydrogen, C.sub.1 -C.sub.6 alkyl or phenyl;
• each of R5 and R6 independently represents hydrogen, C.sub.2 -C.sub.20 alkanoyl, C.sub.3 -C.sub.20 alkenoyl, phenyl, C.sub.1 -C.sub.20 alkyl or C.sub.2 -C.sub.20 alkenyl, wherein the alkanoyl, alkenoyl, alkyl and the alkenyl groups are unsubstituted or substituted by 1 to 3 substituents chosen independently from halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, aryl, aryloxy, cyano, carboxy, (C.sub.1 -C.sub.6 alkoxy) carbonyl, (C.sub.3 -C.sub.4 alkenyl) carbamoyl, aralkylcarbamoyl, arylcarbamoyl and -CONRcRd in which each of Rc and Rd independently is hydrogen or C.sub.1 -C.sub.6 alkyl or Rc and Rd, taken together with the nitrogen atom to which they are linked, form a morpholino or piperidino ring;
• or two of R4, R5 and R6 taken together form a C.sub.4 -C.sub.12 polymethylene chain, which are unsubstituted or substituted by a C.sub.1 -C.sub.12 alkyl, by a C.sub.2 -C.sub.12 alkenyl or by a C.sub.1 -C.sub.12 alkylidene group, wherein the alkyl, alkenyl and alkylidene groups are in turn unsubstituted or substituted by a substituent chosen from halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, cyano, carboxy, (C.sub.1 -C.sub.6 alkoxy)carbonyl, aryloxy and aryl;
• the remaining one being hydrogen or C.sub.1 -C.sub.12 alkyl;
• and the pharmaceutically acceptable salts thereof;
• the process comprising reacting a compound of formula (VIII) ##STR12## wherein R2, R3, R4, R5, R6 are as defined above and X is a leaving group, with a compound of formula (IX) ##STR13## wherein R1 is as defined above and R7 is hydrogen or a lower alkyl chain;
• and, if desired, converting a compound of formula (I) into another compound of formula (I) and/or, if desired, salifying a compound of formula (I) and/or, if desired, converting a salt of a compound of formula (I) into a free compound and/or, if desired, separating a mixture of isomers of a compound of formula (I) into the single isomers.