Synthesis of 2-Aminoquinazolinones via Carbonylative Coupling of ortho-Iodoanilines and Cyanamide
Linda Åkerbladh and Luke R. Odell*
*Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University Box-574, SE-751 23 Uppsala, Sweden, Email: luke.odellorgfarm.uu.se
L. Åkerbladh, L. R. Odell, J. Org. Chem., 2016, 81, 2966-2973.
DOI: 10.1021/acs.joc.6b00249 (free Supporting Information)
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A convenient and efficient synthesis of 2-aminoquinazolin-4(3H)-ones and N1-substituted 2-aminoquinazolin-4(1H)-ones proceeds via carbonylative coupling of readily available ortho-iodoanilines with cyanamide followed by in situ ring closure of an N-cyanobenzamide intermediate. The products were easily isolated by precipitation in good yields for a wide range of substrates.
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In addition, a one-step cascade carbonylation/cyclization method (85 °C, 20 h) can also be employed and is especially suitable for temperature sensitive reactions.
Luke R. Odell, March 3, 2017