In reading about Synthesis of Essential Drugs, I have found in my lab (not a very good book, from a chemical point of view, a lot of mistakes), I have come upon a very strange way to synthesize benzodiazepines (actually triazolobenzodiazepines).
This synthesis starts by a nucleophilic substitution of hydrazine on a 2-chloroquinoline (2,6-dichloro-4-phenylquinoline), boiling this hydrazinoquinoline with orthoacetate in xylene affords triazoloquinoline intermediates.
This intermediate undergoes the key step of the synthesis, a oxidative ring opening of the quinoline with sodium periodate and ruthenium oxide, leading to the triazolobenzophenone.
The 1,3,4-triazole is treated with formaldehyde to provide hydroxymethyl intermediate, subsequent bromination using phosphorous tribromide gives bromomethyltriazole which after spontaneous cyclization with ammonia produces the Alprazolam.
Sorry for the lack of informations, I don't have the two patents concerning this molecule.
This synthesis starts by a nucleophilic substitution of hydrazine on a 2-chloroquinoline (2,6-dichloro-4-phenylquinoline), boiling this hydrazinoquinoline with orthoacetate in xylene affords triazoloquinoline intermediates.
This intermediate undergoes the key step of the synthesis, a oxidative ring opening of the quinoline with sodium periodate and ruthenium oxide, leading to the triazolobenzophenone.
The 1,3,4-triazole is treated with formaldehyde to provide hydroxymethyl intermediate, subsequent bromination using phosphorous tribromide gives bromomethyltriazole which after spontaneous cyclization with ammonia produces the Alprazolam.
Sorry for the lack of informations, I don't have the two patents concerning this molecule.
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