Microwave Heated Flow Synthesis of Spiro-oxindole Dihydroquinazolinone Based IRAP Inhibitors
2014 (English)In: Organic Process Research & Development, ISSN 1083-6160, E-ISSN 1520-586X, Vol. 18, no 11, 1582-1588 p.Article in journal (Refereed) Published
A fast and convenient synthetic route towards spiro-oxindole dihydroquinazolinones as novel and drug-like insulin-regulated aminopeptidase (IRAP) inhibitors is reported. The synthesis is performed using a MW heated continuous flow system employing 200 mm X 3 mm i MW absorbing silicon carbide (SiC) or MW transparent borosilicate tubular reactors. A three-component MW-flow reaction to build up the spiro compounds (9 examples, 4087% yield), using the SiC reactor, as well as a SuzukiMiyaura cross-coupling reaction (71%), employing the borosilicate reactor, are presented with residence times down to 168 s. The continuous MW-flow routes provide a smooth and scalable synthetic methodology towards this class of IRAP inhibitors.
Place, publisher, year, edition, pages
2014. Vol. 18, no 11, 1582-1588 p.
IdentifiersURN: urn:nbn:se:uu:diva-240315DOI: 10.1021/op500237kISI: 000345552100043OAI: oai:DiVA.org:uu-240315DiVA: diva2:776212