SUBSTITUTED 4-ARYL-HEXAHYDRO-7H-IMIDAZOLO[1,5-B][1,2]OXAZINE-7-ONES AND METHOD FOR PRODUCTION THEREOF Russian patent published in 2018 - IPC C07D498/04 A61K31/5365 A61P31/00 A61P25/24 A61P29/00 A61P11/06 

FIELD: chemistry.

SUBSTANCE: present invention relates to a process for the preparation of substituted 4-aryl-hexahydro-7H-imidazole[1,5-b][1,2]oxazine-7-ones of the general formula:

showing inhibitory activity against phosphodiesterase of subtype 4. Method consists in the fact that 5,6-dihydro-4H-1,2-oxazine-N-oxides of general formula:

are sequentially treated with trimethylsilyl bromide with a nitrogenous base and metal bromide in an aprotic solvent medium at a reduced temperature followed by treatment of the corresponding bromides with sodium azide at elevated temperature in an aprotic solvent medium to give the corresponding 3-azidomethyl-5,6-dihydro-4H-1,2-oxazines of the general formula:

that are reacted with sodium cyanoborohydride in a protonic acid, followed by catalytic reduction of the corresponding 3-azidomethyl-1,2-oxazines of the general formula:

hydrogen in the presence of a metal catalyst in a low-molecular alcohol medium and treating the reaction mixture with a carbamoylating reagent with a nitrogenous base in an aprotic solvent. Invention also relates to a novel compound 4-[3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl]hexahydro-7H-imidazolo[1,5-b][1,2]oxazine-7-one.

EFFECT: compounds having inhibitory activity against phosphodiesterase of subtype 4.

4 cl, 1 dwg, 1 tbl, 13 ex