Oxazolidinone combinatorial libraries, compositions and methods of preparation

A method of preparing combinatorial libraries of compounds of the formula Ib, comprising the steps of:

• a) attaching a plurality of aryl oxazolidinones to a plurality of solid supports;
• b) functionalizing the 4-position of the aryl groups of the attached oxazolidinones to produce an R1 substituent;
• and, optionally,
• c) removing the oxazolidinones from the solid supports;
• wherein compounds of formula Ib have the structure:
• wherein R2, R3, R4 and R5 are, independently, hydrogen alkyl, heteroalkyl, heteroaryl or an electron withdrawing group;
• R6 is acyl or sulfonyl;
• and
• R1 is one of the following functional groups:
• C(O)NR7R8, wherein R7 and R8 are, independently, hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;
• C(O)OR9, wherein R9 is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;
• C(O)R10, wherein R10 is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;
• SR11, wherein R11 is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;
• S(O)2R11, wherein R11 is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;
• S(O)R11, wherein R11 is hydrogen, alkyl, heteroalkyl, aryl or heteroaryl;
• NR12R13, wherein R12 and R13 are, independently, hydrogen, acyl, sulfonyl, alkyl, heteroalkyl, aryl or heteroaryl;
• 2-oxazolyl, wherein R14 is at the 4-position and R15 is at the 5-position of the oxazolyl, and wherein R14 and R15 are, independently, hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or an electron withdrawing group;
• 2-aminothiazolyl, wherein R16 is at the 4-position and R17 is at the 5-position of the thiazole, and wherein R16 and R17, are, independently, hydrogen, alkyl, heteroalkyl, aryl, heteroaryl or an electron withdrawing group;
• CH2NR18R19, wherein R18 and R19 are, independently, hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, acyl or sulfonyl;
• and
• wherein the aryl oxazolidinones in step a) comprise the structure
• wherein R2, R3, R4 and R5 are defined above;
• Q1 is selected from —C(O)O-PG, —S-PG, —CH(OC1-4alkyl)2, where PG is a protecting group;
• and
• Q2 is N3, wherein the resin includes a carbonyl containing moiety and attaching the plurality of aryl oxazolidinones to the plurality of solid supports in step a comprises converting Q2 to an iminophosphorane or an amine and reacting the iminophosphorane or the amine with the carbonyl moiety of the resin to form an imine.