Synthesis of 2,3-Dihydro-4(1H)- quinazolinones

Abstract

An improved procedure for the synthesis of 2-substituted 2,3-dihydro-4(1H)-quinazolinones through diastereomer separation of the corresponding quinazolinones derivatives is presented. The determination of their absolute configurations was obtained by X-Ray diffraction.

Synthesis, Resolution and Absolute Configuration of 2,3-Dihydro-2-<i>Tert</i>-Butyl-3-<i>N</i>-Benzylquinazolin-4-One: A Possible Chiral Auxiliary for Synthesis of <i>β</i>-Amino Cyclohexancarboxylic Acid

“…The present paper describes the synthesis and resolution of 2,3-dihydro-2-tert-butyl-3-N-benzylquinazolin-4-one rac-11 as a possible precursor of cis-and trans-2-aminocyclohexanecarboxylic acids. In this compound, it is important to mention that the tert-butyl group at C(2) adopts a pseudoaxial position, as shown by analysis of X-ray diffraction [10]- [12], and we would expect higher induction in asymmetric hydrogenation reaction: the ad-dition of the hydrogen on the syn face, leading to the exclusive formation of the only one diastereomer.…”

“…of NaHMDS in hexane (1.0 M). The resulting solution was stirred at −78˚C for 10 min and treated successively with the resolution agent (N-phthalyl-L-alanine chloride) [12] [24]. The mixture was stirred at the same temperature for 1 h and treated with saturated ammonium chloride solution and then with water.…”

“…Enantiomerically pure quinazolinone 1 was reduced diastereoselectively by hydrogenation with PtO 2 , resulting in octahydroquinazolinone diastereomers. Both cis-annelated derivatives (2 and 3) could be epimerized in the presence of t-BuO − K + , giving the corresponding trans-fused derivatives (4 and 5) respectively in good yields (Scheme 1) [10]- [12].…”

Synthesis of Condensed Heterocycles, Containing Partially Saturated Pyrimidine Nuclei, from Aromatic Pyrimidine Derivatives

“…Catalytic reduction of the C2 substituent free quinazolin‐4(3 H )‐ones 1 over palladium on charcoal or platinum oxide at ambient temperature afforded 2,3‐dihydro‐4(1 H )‐quinazolines 2 in 92–95% yields (Scheme ).…”

“…These transformations allow increasing the structural diversity and changing the overall geometry of those heterocycles. Catalytic reduction of the C2 substituent free quinazolin-4(3H)ones 1 over palladium on charcoal [22] or platinum oxide [23] at ambient temperature afforded 2,3-dihydro-4(1H)quinazolines 2 in 92-95% yields (Scheme 1).…”