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

• Published in: Combinatorial chemistry & high throughput screening Vol. 3; no. 2; p. 139
• Main Authors: South, M S, Case, B L, Dice, T A, Franklin, G W, Hayes, M J, Jones, D E, Lindmark, R J, Zeng, Q, Parlow, J J
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.04.2000
• Subjects: Amines - chemical synthesis; Benzamides - chemical synthesis; Chromatography, High Pressure Liquid; Combinatorial Chemistry Techniques - methods; Mass Spectrometry; Molecular Structure; Polymers - chemistry
• ISSN: 1386-2073
• DOI: 10.2174/1386207003331724

A parallel solution-phase library synthesis of functionalized diaminobenzamides is described. The four-step library synthesis is accomplished using polymer-assisted solution-phase (PASP) synthesis techniques. This high-yielding, multi-step sequence utilizes sequestering resins for the removal of reactants, reactant by-products, and employs a resin capture/release strategy as a key library synthesis step. Step one of the sequence relies on the displacement of an activated fluoro-group from the aromatic ring of 1a, b with a variety of primary amines to introduce the first diversity position. Step two is hydrolysis of the benzoate ester to a benzoic acid which is subsequently 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 of a benzoic acid with a variety of primary amines to give the aminonitrobenzamides 5a, b and introduces the second diversity position. Step four is the parallel reduction of the aminonitrobenzamides 5a, b to the functionalized diaminobenzamides 6a, b. This library synthesis proceeds with high overall purities which average 80 % over the 4-step sequence.