Efficient solid-phase synthesis of 3-substituted-5-oxo-5H-thiazolo[2,3-b]-quinazoline-8-carboxamides under mild conditions with two diversity positions

J Comb Chem. 2007 Nov-Dec;9(6):912-5. doi: 10.1021/cc700122a. Epub 2007 Oct 2.

Abstract

Highly efficient solid-phase synthesis of thiazolo[2,3,b]quinazolines under mild conditions was developed using resin-bound 2-amino-terephthalamic acid, Fmoc-NCS, and bromoketones. Primary amines immobilized to an acid-cleavable backbone amide linker were acylated with 1-methyl-2-aminoterephtalate. Following cleavage of the methyl ester, Fmoc-NCS was used to form a resin-bound thiourea. Bromoketones were subsequently added to form an aminothiazole ring and the cyclization was performed using DIC/HOBt to afford thiazolo[2,3,b]quinazolines. Highly efficient solid-phase synthesis is amenable to high throughput/combinatorial synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Antifungal Agents / chemical synthesis*
  • Combinatorial Chemistry Techniques*
  • Models, Chemical
  • Quinazolines / chemistry*
  • Thiazoles / chemistry*

Substances

  • Amides
  • Antifungal Agents
  • Quinazolines
  • Thiazoles