Combinatorial solid phase synthesis of a library of indole derivatives

A process for producing a plurality of indole compounds of formula:

• ##STR21## wherein:
• R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5, which are the same or different, are each hydrogen or a structural diversity element, with the proviso that at least one of R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 is different from hydrogen;
• R.sub.0 is --NR.sub.6 R.sub.7 or --OR.sub.8, wherein R.sub.6, R.sub.7, and R.sub.8, which are the same or different, are each hydrogen or a structural diversity element;
• A is CH or N, and may occupy any of the unsubstituted positions of the phenyl ring;
• and
• n is zero or an integer from 1 to 4;
• which process comprises the steps of:
• (a) coupling to a solid support a first scaffold of formula:
• ##STR22## wherein:
• R.sub.4 and R.sub.5, which are the same or different, are each hydrogen or a structural diversity element;
• A is CH or N, and may occupy any of the unsubstituted positions of the phenyl ring;
• n is zero or an integer from 1 to 4;
• L is a leaving group;
• and
• X is hydrogen or an activating group;
• (b) reacting said first scaffold coupled to the solid support with a second scaffold of formula:
• ##STR23## wherein R.sub.2 and R.sub.3, which are the same or different, are each hydrogen or a structural diversity element;
• in the presence of a transition metal as catalyst, and optionally in the presence of a Cu(I) salt, to give indole compounds of formula (Ia) supported on the solid support:
• ##STR24## (c) optionally alkylating, acylating or sulfonylating the said compounds of formula (Ia) at the nitrogen atom in position 1 to give indole compounds of formula (Ib):
• ##STR25## wherein R.sub.1 is a structural diversity element;
• (d) optionally cleaving the said compounds of formula (Ia) or (Ib) from the solid support to give indole compounds of formula (I).