Compositions containing N-amino- and N-hydroxy-quinazolinones and methods for preparing libraries thereof
AssigneeSepracor Inc.
InventorYun Gao
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Abstract
The present invention is directed to certain N-amino- and N-hydroxy-quinazolinone compounds and synthetic methods for synthesis thereof, which compounds may find use in combinatorial libraries. More specifically, the invention is directed to the synthesis of 3-hydroxy- and 3-amino-4(1H)-quinazolinones via the reaction of an appropriate 2-aminobenzamide compound with a carboxylic acid or acyl halide at ambient temperature performed on a solid support or in solution.
Claims14
A method for synthesizing a 3-hydroxy quinazolinone, comprising:
- (a) reacting a free amine moiety bound to a solid support with an appropriate isatoic anhydride to afford a 2-aminobenzamide bound to said solid support;
- (b) reacting said 2-aminobenzamide with a carboxylic acid in the presence of an activating agent to afford a 3-hydroxy quinazolinone bound to said solid support;
- and
- (c) reacting said 3-hydroxy quinazolinone bound to said solid support under acidic hydrolysis conditions to yield unbound 3-hydroxy quinazolinone.
A method of synthesizing an N-hydroxy quinazolinone on a solid support which comprises:
- (a) selecting a solid support comprising at least one compound covalently attached to said solid support which compound comprises a moiety having at least one nucleophilic site;
- (b) reacting said moiety of said compound covalently attached to said solid support with a diverse array of isatoic anhydrides in an aprotic organic solvent at an appropriate temperature range to afford a 3-alkoxy-2-aminobenzamide;
- (c) reacting said 3-alkoxy-2-aminobenzamide bound to said solid support with a carboxylic acid in the presence of an activating agent or an acid chloride and a coupling agent to afford a 3-alkoxy quinazolinone bound to said solid support.
A method for synthesizing a 3-amino quinazolinone, comprising:
- (a) reacting a hydrazine moiety with a free amino group bound to a solid support with an appropriate isatoic anhydride to afford a 1,2 disubstituted anthraniloylhydrazine;
- (b) reacting said 1,2 disubstituted anthraniloylhydrazine with a carboxylic acid in the presence of an activating agent to afford a 3-amino quinazolinone bound to said solid support, and
- (c) reacting said 3-amino quinazolinone bound to said solid support under acidic hydrolysis conditions to yield unbound 3-hydroxy quinazolinone.
A method of synthesizing an N-amino quinazolinone on a solid support which comprises:
- (a) selecting a solid support comprising at least one compound covalently attached to said solid support which compound comprises a moiety having at least one nucleophilic site;
- (b) reacting said moiety of said compound covalently attached to said solid support with a diverse array of isatoic anhydrides in an aprotic solvent to afford a 1,2 disubstituted anthraniloyl hydrazine;
- and
- (c) reacting said 1,2 disubstituted anthraniloyl hyrdrazine bound to said solid support with a carboxylic acid in the presence of a coupling agent to afford a 3-hydrazino-quinazolinone bound to said solid support.
Dependencies are inferred from the claim text.