Solid-phase supported synthesis: a possibility for rapid scale-up of chemical reactions.
The direct scale-up of a solid-phase synthesis has been demonstrated with 4-(2-amino-6-phenylpyrimidin-4-yl)benzamide and an arylsulfonamido-substituted hydroxamic acid derivative as examples. These compounds were obtained through combinatorial chemistry and solution-phase synthesis was used in parallel to provide a comparison. By applying highly loaded polystyrene-derived resins as the solid support, a good ratio between the product and the starting resin is achieved. We have demonstrated that the synthesis can be scaled up directly on the solid support, successfully providing the desired compounds easily and quickly in sufficient quantities for early development demands.
Meisenbach
M
M
Chemical and Analytical Development, Novartis Pharma AG, 4002 Basel, Switzerland. mark.meisenbach@novartis.com
Allmendinger
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T
Mak
C P
CP
D002625:Chemistry, Organic / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006877:Hydroxamic Acids / Q000737:chemistry; D008956:Models, Chemical; D011743:Pyrimidines / Q000737:chemistry; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods; D013997:Time Factors
D006877:Hydroxamic Acids; D011743:Pyrimidines