Process for preparing diaminophenothiazinium compounds

摘要

Process for preparing compounds of the diaminophenothiazinium type of formula (II) below. The products have a high degree of purity and are useful for the preparation of medicaments.;
In which the R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 groups having the same definition as in formula (I), and R representing a group chosen from:
a phenyl or benzyl group, optionally substituted with one or more functions chosen from: a C1-C4 alkyl, a halogen atom, a C1-C4 haloalkyl and a nitro group,a linear, branched or cyclic C1-C8 alkyl group,a C1-C8 alkylamino group,a C1-C8 alkoxy group,a phenyloxy or benzyloxy group optionally substituted on the aromatic nucleus with one or more functions chosen from: a C1-C4 alkyl, a halogen atom, a C1-C4 haloalkyl and a nitro group,Z representing an atom chosen from O and S.

主权项

1. A process for preparing a compound corresponding to formula (I) below: in which each of R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 is chosen, independently of the others, from the group constituted of:
a hydrogen atom,saturated or unsaturated, linear, or branched C1-C6 alkyl groups, or C3-C6 cycloalkyl groups, optionally substituted with one or more functions chosen from a halogen atom, and a C1-C6 alkoxy, C alkoxycarbonyl or —CONH2 function,aryl groups optionally substituted with one or more functions chosen from: a C1-C4 alkyl, a halogen atom, and a C1-C6 alkoxy, C1-C6 alkyloxycarbonyl or —CONH2 function,
X− represents an organic or inorganic anion, wherein the process comprises at least one step during which a compound of formula (II): in which R represents a group chosen from:
a phenyl or benzyl group, optionally substituted with one or more functions chosen from: a C1-C4 alkyl, a halogen atom, a C1-C4 haloalkyl and a nitro group,a phenyloxy or benzyloxy group optionally substituted on the aromatic nucleus with one or more functions chosen from: a C1-C4 alkyl, a halogen atom, a C1-C4 haloalkyl and a nitro group, Z represents an atom chosen from O and S, is subjected to a purification step, this step comprising at least one filtration through a filtration support chosen from: a silica gel, a neutral, basic or acidic alumina gel, a microporous membrane, a resin grafted with metal-capturing groups, and fibers grafted with metal-capturing groups,and thereafter a step for deprotection of the amine of the phenothiazine ring of the compound of formula (II), wherein the deprotection step of compound (II) to produce compound (I) is achieved in a one-pot process.