METHOD FOR THE OBTAINMENT OF 2-ALKOXY-6-[1-(2,6-DIFLUOROPHENYL)CYCLOPROPYL]-5-METHYLPIPERIMIDINE-4(3H)-ON Russian patent published in 2018 - IPC C07D239/36 

FIELD: chemistry.

SUBSTANCE: invention relates to the improved process for the preparation of the 2-alkoxy or 2-(C_5-6cycloalkyl)oxy-6-[1-(2,6-difluorophenyl)cyclopropyl]-5-methylpyrimidine-4(3H)-on, which are the bioisosteric analogs of the non-nucleoside HIV-1 reverse transcriptase inhibitors. Method consists in boiling the 6-[1-(2,6-difluorophenyl)cyclopropyl]-5-methyl-2-(nitroamino)pyrimidine-4(3H)-on, which is previously obtained by means of condensation of nitroguanidine with the ethyl-3-[1-(2,6-difluorophenyl)cyclopropyl]-2-methyl-3-oxopropanoate, with the corresponding alcohol in the presence of amine, followed by evaporation of the reaction mass and by the product recovery. Boiling process is carried out using as the amine of N-methylpiperidine, which is taken in excess with respect to the starting nitroamine. Starting corresponding alcohol is used in bulk excess in relation to N-methylpiperidine. Product is isolated by successive four-fold addition and distillation under reduced pressure of xylene, and before the last distillation of xylene, the adsorptive filtration of the xylene solution is carried out. Method allows to obtain the new and known compounds with the higher yield (84–94 % instead of 64 %) and with the higher purity.

EFFECT: method is also simpler, because it does not require the use of chromatographic recovery and purification of products.

1 cl, 8 ex