SYNTHESIS OF SUBSTITUTED GAMMA-CARBOLINES CONDENSED WITH A HETEROCYCLE Russian patent published in 2023 - IPC C07D471/16 A61K31/4985 A61P25/00 

FIELD: pharmaceutical chemistry.

SUBSTANCE: methods for preparing compounds of formulas 1J, 1I, 1F. In formula 1J, R is selected from H and C_1-4 alkyl, Q is selected from 4-(4-fluorophenyl)-4-oxobutyl and 3-(4-fluorophenoxy)propyl. The substituted heterocycle-fused gamma-carbolines of formula 1J are useful in the treatment of diseases involving the 5-HT_2A receptor, the serotonin transporter (SERT), pathways involving the D₁ and/or D₂ dopamine receptor signaling systems, and/or the μ-opioid receptor. The process for preparing a compound of formula 1J is carried out by reacting in toluene a compound of formula 1E with a transition metal catalyst selected from the group consisting of groups 8-11 of the Periodic Table, and optionally a base and optionally an alkali metal or ammonium iodide or bromide, and optionally monodentate or bidentate ligand to obtain an intermediate product of formula 1F. The protecting group on the piperidine nitrogen of the compound of formula 1F is then removed to give a compound of formula 1I which is alkylated with a suitable alkylation reagent to give a compound of formula 1J in free or salt form. The method also optionally includes converting a compound of formula 1J in free form to a compound of formula 1J in salt form. Substituents in formulas 1E, 1F, 1I are as indicated in the claims.

EFFECT: increased yield and purity of the resulting substituted heterocycle-condensed gamma-carboline of formula 1J due to the use of toluene as a solvent.

39 cl, 9 ex, 4 tbl