Dry HCl in parallel synthesis of fused pyrimidin-4-ones.

The parallel solution-phase synthesis of substituted thieno[2,3- d]pyrimidin-6-carboxylic acids has been accomplished. This strategy relies on a cyclization of 2-aminothiophen-3,5-dicarboxylates with a set of nitriles, followed by hydrolysis to construct the library of corresponding acids. The convenient procedure for use and dosage of dry HCl for the reaction was elaborated and adapted for semiautomated solution-phase parallel synthesis. With the use of another (hetero)aromatic ortho-aminocarboxylate, mini-libraries of diverse fused pyrimidin-4-ones were synthesized. The scope and limitations of the approach are discussed.

Synthesis of thieno[2,3-d]pyrimidin-2-ylmethanamine combinatorial library with four diversity points.

The parallel solution-phase synthesis of more than 230 substituted thieno[2,3-d]pyrimidin-2-ylmethanamines has been accomplished. This strategy is based on the cyclization of 2-aminothiophen-3-carboxylates with chloroacetonitrile to construct the thieno[2,3-d]pyrimidine core with two diversity points. Derivatization of the active chlorine and functionalization of C-4 position of the pyrimidine ring allow the introduction of other diversity points. The products containing ester groups at the 6-position of the thieno[2,3-d]pyrimidine were used in amide synthesis. Simple manual techniques for parallel reactions, coupled with simple purification procedures, gave highly pure final products. The scope and limitations of the approach are discussed.