Abstract
Quinazolin-4(3H)-ones have been prepared in one step from 2-aminobenzamides and orthoesters in the presence of acetic acid. Simple 2-aminobenzamides were easily converted to the heterocycles by refluxing in absolute ethanol with 1.5 equivalents of the orthoester and 2 equivalents of acetic acid for 12–24 h. Ring-substituted and hindered 2-aminobenzamides as well as cases incorporating an additional basic nitrogen required pressure tube conditions with 3 equivalents each of the orthoester and acetic acid in ethanol at 110 °C for 12–72 h. The reaction was tolerant towards functionality on the benzamide and a range of structures was accessible. Workup involved removal of the solvent under vacuum and either recrystallization from ethanol or trituration with ether-pentane. Several 5,6-dihydropyrimidin-4(3H)-ones were also prepared from 3-amino-2,2-dimethylpropionamide. All products were characterized by melting point, FT-IR, 1H-NMR, 13C-NMR, and HRMS.
Highlights
Quinazolin-4(3H)-ones are valuable scaffolds in pharmaceutical chemistry due to their diverse biological activities
We report the synthesis of 2-alkyl- and 2-arylquinazolin-4(3H)-ones from inexpensive
The process is similar to earlier acid-catalyzed processes reported by our group for the preparation of 2-substituted 2,3-dihydroquinazolin-4(1H)-ones [7] and benzimidazoles [8] as well as for a synthesis of benzimidazo[1,2-c]quinazolines described by others [9]
Summary
Quinazolin-4(3H)-ones are valuable scaffolds in pharmaceutical chemistry due to their diverse biological activities. Some examples of 2-alkyland 2-arylquinazolin-4(3H)-ones currently on the market include the sedative-hypnotics methaqualone (quaalude, 1) [2] and afloqualone (2) [3,4] as well as the antifungal albaconazole (3) [5]. We report the synthesis of 2-alkyl- and 2-arylquinazolin-4(3H)-ones from inexpensive. The process is similar to earlier acid-catalyzed processes reported by our group for the preparation of 2-substituted 2,3-dihydroquinazolin-4(1H)-ones [7] and benzimidazoles [8] as well as for a synthesis of benzimidazo[1,2-c]quinazolines described by others [9]. Using the conditions disclosed a small library of substituted quinazolin-4(3H)-ones has been generated with high yields (Figure 1). We report the synthesis of a modest selection of 5,6-dihydropyrimidin-4(3H)-ones from
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