Synthesis process, and crystalline form of 4-{ 3-[cis-hexahydrocyclopenta[c]pyrrol-2(1h)-yl]propoxy} benzamide hydrochloride and pharmaceutical compositions containing it
ROBERT NICOLAS,GAILLARD MARINA,LECOUVE JEAN-PIERRE,LERESTIF JEAN-MICHEL,MEUNIER LOIC,LETELLIER PHILIPPE
申请号：
NZ60047412
公开号：
NZ600474A
申请日:
2012.06.06
申请国别(地区):
NZ
年份:
2013
代理人:
摘要：
Process for the industrial synthesis of the compound of formula (I) (4-{ 3-[cis-hexahydrocyclopenta[c]pyrrol-2(1H)-yl]propoxy} benzamide hydrochloride) characterised in that the compound of formula (II) is reacted with ammonia at a temperature greater than 100 degrees C to form the compound of formula (III) which is reduced to yield the bicyclic amine of formula (IV) which latter compound is subsequently subjected to - either to a coupling reaction, under basic conditions in a polar medium, with a compound of formula (V) wherein the substituents are as disclosed in the specification, - or to reductive amination, in an acid medium, with a compound of formula (V) wherein the substituents are as disclosed in the specification, - or to reductive amination with the compound of formula (V") to yield the free base of the compound of formula (I), which is placed in the presence of HCl (hydrochloric acid) to form the compound of formula (I), which is isolated in the form of a solid. Also disclosed are the compounds of formula (V) and (V) in particular 4-(3,3-diethoxypropoxy)benzamide the use of compounds of formulae (V), (V) and (V) for preparing a compound of formula (I) crystalline form I of a compound of formula (I) characterised by x-ray powder diffraction spectra, Raman spectra and solid state NMR spectra. Further disclosed is the use of a compound of formula (I) for the manufacture of a medicament for the treatment of the histaminergic system the treatment of cognitive and psycho-behavioural disorders associated with cerebral ageing and with neurodegenerative diseases, and also for the treatment of mood disorders, attention-deficit hyperactivity syndrome, obesity and pain the treatment of cognitive and psycho-behavioural disorders associated with Alzheimers disease, Parkinsons disease, Picks disease, Korsakoffs disease, Lewy body dementias, frontal and subcortical dementias, frontotemporal dementias and vascular dementias.
