Methods for synthesizing libraries of dihydro-quinazolinones

A method for synthesizing 2,3-dihydro-3-alkoxy-4(1H)-quinazolinones, which comprises:

• (a) selecting a solid support comprising an alkoxylamine moiety covalently attached to said solid support;
• (b) reacting said alkoxylamine moiety covalently attached to said solid support with one or more isatoic anhydrides to afford a 2-amino-O-alkyl benzhydroxamic acid covalently attached to said solid support;
• and
• (c) reacting said 2-amino-O-alkyl benzhydroxamic acid covalently attached to said solid support with one or more aldehydes in the presence of a Lewis acid catalyst to afford a 2,3-dihydro-3-alkoxy-4(1H)-quinazolinone covalently attached to said solid support.

A method of synthesizing 2,3-dihydro-3-alkoxy-4(1H)-quinazolinones of the formula (IV):

• which comprises:
• reacting one or more 2-amino-O-alkyl benzhydroxamic acids with an aldehyde in the presence of a Lewis acid catalyst, wherein said aldehyde has the formula R9CHO;
• wherein R1, R2, R3 and R4 are independently hydrogen, halogen, C1-C6 alkyl, C1-C6 alkenyl, hydroxy, C1-C6 alkoxy, NO2, SO2Ph, phenyl, SO2NR6R7, NR6R7, OCOR8, SR8, CO2R8, NHCOR8;
• or R1 and R2, R2 and R3, or R3 and R4 can be taken together to form a 5-7 membered carbocyclic aromatic group or heterocyclic aromatic group wherein the heterocyclic aromatic group is selected from the group consisting of furyl, thienyl, pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, and indolyl;
• R5 is hydrogen, C1-C6 alkyl, C1-C6 alkenyl, benzyl, phenyl, CH2-furyl, or CH2-pyridyl, wherein the alkyl, alkenyl, benzyl, phenyl, furyl and pyridyl groups may be further substituted with substituents independently selected from the group consisting of C1-C6 alky, C1-C6 alkoxy, halogen, NO2, CF3, and CN;
• R6 and R7 are independently H, or C1-C6 alkyl, or taken together are (CH2)f wherein f is 3-6;
• R8 is hydrogen, C1-C6 alkyl, benzyl, phenyl, or substituted phenyl with 1-3 substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, halogen, NO2, CF3, and CN;
• R9 is hydrogen, C1-C6 branched or straight alkyl, C1-C6 branched or straight alkenyl, C1-C6 aralkyl, C1-C6 aralkenyl, C1-C10 cycloalkenyl, C1-C10 bicycloalkenyl, C1-C6 cycloalkyl, phenyl, phenyl substituted with 1-3 substituents independently selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 alkoxy, SR8, OR8, CF3, OCF3, and NO2, a 5-10 membered carbocyclic aromatic group or heterocyclic aromatic group wherein the heterocyclic group is selected from the group consisting of furyl, thienyl, pyridyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridazinyl, pyrimidinyl, pyrazinyl, and indolyl, wherein the heterocyclic aromatic group can be further substituted with a phenyl group which may be substituted with 1-3 substituents independently selected from the group consisting of CF3, halogen, C1-C6 alkyl, C1-C6 alkoxy, and OCOR8;
• R10 is H, C1-C6 alkyl, C1-C6 alkenyl, phenyl or phenyl substituted with 1-3 substituents independently selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, halogen, NO2, CF3, and CN;
• and
• J is C.