http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-044341-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_24e76490bed88751680a5fef9bc73892 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P31-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D498-04 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D487-04 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D513-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D487-04 |
| filingDate | 2004-05-14-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationDate | 2005-09-07-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-044341-A1 |
| titleOfInvention | PROCESS FOR SYNTHESIS OF INTERMEDIARIES OF BETALACTAMASA INHIBITORS |
| abstract | Bicyclic heteroarylcarboxaldehydes are useful as intermediates for the preparation of beta-lactamase inhibitors. Claim 1: A process for the preparation of bicyclic heteroarylcarboxaldehydes of formula (1), wherein: Y is (CH2) n; n is 1 or 2; X is NR; OR; S or CH2; R is C1-6 alkyl, or (C1-6) arylalkyl; provided that n is 2 when X is NR or O; comprising the steps of: a) nitrosating an amino acid of the formula (2), wherein X and Y are defined as described above, with a nitrosant reagent in order to form a nitrous compound of formula (3), in where X and Y are defined as set forth above; b) reacting the nitrous compound of formula (3) with a dehydrating agent and neutralizing with inorganic base, in order to form the ilium of formula (4), wherein X and Y are defined as described above; c) reacting the ilide of formula (4) with a propriolate ester of HC ° CCO2R1, where R1 is C1-6 alkyl, in aprotic solvents, so as to form a mixture of heteroaryl-bicyclic-3-carboxylate ester of formula (5 ) and heteroaryl-bicyclic-2-carboxylate ester of formula (6), wherein R1, X and Y are defined as described above; d) reacting the mixture of heteroaryl-bicyclic-3-carboxylate ester of formula (5) and heteroaryl-bicyclic-2-carboxylate ester of formula (6) with a MOR5 hydrolyzing reagent where M is an alkali metal or R4N where R4 it is straight or branched C1-6 alkyl, when R5 is H, in an alcohol solvent, or when M is an alkali metal and R5 is C1-6 alkyl, in an aqueous alcohol solvent, to preferably form a salt of the formula (7) wherein X, Y and M are defined as described above; e) isolating the salt of formula (7), f) reacting the salt of formula (7) with acid, to form heteroaryl-bicyclic-2-carboxylic acid of formula (8) wherein X and Y are defined as described above; g) reacting the heteroaryl-bicyclic-2-carboxylic acid of formula (8) or salts thereof, with an acid halide reagent or coupling reagent, in order to form an activated intermediate of the formula (9) where Q is an output group formed from the coupling reagent or acid halide reagent and wherein X and Y are defined as described above; h) reacting an activated intermediate of formula (9) or heteroaryl-bicyclic-carboxylic acid of formula (8) with a substituted hydroxylamine of the formula R3NHOR2, where R2 and R3 are independently C1-6 alkyl, in the presence of a base organic or inorganic base, in order to provide an amide of formula (10), where X, Y, R2 and R3 are defined as set forth above; i) reducing the amide of formula (10) with a reducing agent, in order to achieve a bicyclic heteroarylcarboxaldehyde of formula (1), wherein X and Y are defined as set forth above, and isolating the heteroarylcarboxaldehyde of formula (1). |
| priorityDate | 2003-05-16-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
Incoming Links
Total number of triples: 17.