Traceless Solid-Phase Synthesis of Trisubstituted Quinazolines

ACS Comb Sci. 2015 Aug 10;17(8):470-3. doi: 10.1021/acscombsci.5b00060. Epub 2015 Jul 13.


A traceless polymer-supported synthesis of 4-benzoylquinazolines was developed using the following commercially available building blocks: Fmoc-α-amino acids, 2-nitrobenzensulfonyl chlorides and α-bromoacetophenones. The acyclic intermediates underwent base-catalyzed rearrangement involving C-C and N-N bond formation followed by ring expansion and yielded resin-bound dihydroquinazoline-2-carboxylic acids. After they were released from the resin by treatment with trifluoroacetic acid, base-mediated decarboxylation produced the target quinazolines in moderate-to-high yields and purities.

Keywords: amino acids; bromoketone; indazole oxides; nitrobenzenesulfonyl chlorides; quinazolines; solid-phase synthesis; traceless synthesis; α-bromoacetophenones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / chemistry
  • Amino Acids / chemistry
  • Fluorenes / chemistry
  • Molecular Structure
  • Nitrobenzenes / chemistry
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry


  • Acetophenones
  • Amino Acids
  • Fluorenes
  • N(alpha)-fluorenylmethyloxycarbonylamino acids
  • Nitrobenzenes
  • Quinazolines
  • phenacyl bromide
  • 2-nitrobenzenesulfenyl chloride