FIELD: chemistry; medicine.
SUBSTANCE: present invention relates to a method of producing (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline-6,7-diol (formula I) and (6aR,10aR)-7-propyl-6,6a,7,8,9,10,10a,11-octahydro-[1,3]dioxolo[4',5':5,6]benzo[1,2-g]quinoline (formula Ib) and salts thereof, which are used in treating neurodegenerative diseases and disorders, such as Parkinson's disease.
Invention also relates to novel intermediate compounds from said method. Method of producing a compound of formula (I) from a compound of formula (Ib) involves the following steps. Step 0), sub-step (i) reacting compound (A1) with 3-chloropropane-1-amine to obtain compound (a2i) or sub-step (S1) with reacting compound (a6i) with tert-butyl-2-bromoacetate and zinc to form a mixture, then treatment of mixture from substage (S1) with acetic acid, then reaction of said mixture with 3-chloropropane-1-amine hydrochloride to obtain compound (a2i). Step 1), sub-step (ii) of reducing compound (a2i) obtained in sub-step (i) or sub-step (S1), to obtain compound (a2ii), then sub-step (iii) of separating compound (a2ii) using L-tartaric acid to obtain A2-hemi-L-tartrate, according to the following reaction scheme:
then performing a step, in which compound (A2) or its salt reacts to obtain compound (A3) or its salt according to the following reaction scheme:
then the compound (A3) or its salt is reacted to obtain compound A4 or its salt according to the following scheme reactions:
,
then compound (A4) or its salt is reacted to obtain compound (A5) or its salt according to the following reaction scheme:
,
then the compound (A5) or its salt is reduced to obtain compound (Ib) or its salt according to the following scheme reaction:
.
EFFECT: providing improved methods of producing desired compounds (I) and (Ib), including high output of products and avoiding or reducing syntheses which interfere with large-scale production.
21 cl, 11 ex
