Multi-step polymer-assisted solution-phase (PASP) library synthesis of functionalized diaminobenzamides

A parallel solution-phase library synthesis of functionalized diaminobenzam ides is described. The four-step library synthesis is accomplished using po lymer-assisted solution-phase (PASP) synthesis techniques. This high-yieldi ng, multi-step sequence utilizes sequestering resins for the removal of rea ctants, reactant by-products, and employs a resin capture/release strategy as a key library synthesis step. Step one of the sequence relies on the dis placement of an activated fluoro-group from the aromatic ring of la, b with a variety of primary amines to introduce the first diversity position. Ste p two is hydrolysis of the benzoate ester to a benzoic acid which is subseq uently captured on a polyamine resin, washed, and released to give 4a, b in pure form. Step three utilizes PASP resins to mediate the amide coupling o f a benzoic acid with a variety of primary amines to give the aminonitroben zamides 5a, b and introduces the second diversity position. Step four is th e parallel reduction of the aminonitrobenzamides 5a, b to the functionalize d diaminobenzamides 6a, b. This library synthesis proceeds with high overal l purities which average 80 % over the 4-step sequence.