Multi-Step Polymer-Assisted Solution-Phase (PASP) Library Synthesis of Functionalized Diaminobenzamides
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.
Source: Combinatorial Chemistry & High Throughput Screening, Volume 3, Number 2, April 2000 , pp. 139-151(13)
Publisher: Bentham Science Publishers
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Abstract:
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 percent over the 4-step sequence.
Keywords: Multi step polymer; Assisted Solution phase; Library synthesis; Functionalized Diaminobenzamides
Language: English
Document Type: Regular paper
DOI: 10.2174/1386207003331724
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