PROCESS FOR THE INDUSTRIAL SYNTHESIS OF LURASIDONE

摘要

Disclosed is a process for the industrial synthesis of Lurasidone from (1R,2R)-cyclohexane-1,2-diyldimethanol (1), 3-(piperazin-1-yl)benzo[d]isothiazole (3) and (3aR,4R,7R,7aS)-3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1,3-dione (6).). Said process is optimised to obtain Lurasidone with high yields and high purities by preparing highly pure synthesis intermediates, using critical raw materials and reagents in amounts close to the stoichiometric amounts, increasing productivity and reducing the costs and environmental impact of the process.;

主权项

1. A process for the preparation of Lurasidone starting from (1R,2R)-cyclohexane-1,2-diyldimethanol 1 which comprises the following steps:
a) mesylating 1 to give (1R,2R)-1,2-bis(methanesulfonyloxymethyl)cyclohexane 2; b) reacting 2 with 3-(piperazin-1-yl)benz[d]isothiazole 3 in an organic solvent in the presence of a calcium or magnesium oxide or hydroxide, to give (3aR,7aR)-4′-(benz[d]isothiazol-3-il)octahydrospiro[2H-isoindol-2,1′-piperazinium] methanesulfonate 4; c) reacting 4 obtained in step b) with (3aR,4S,7R,7aS)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione 5 to give Lurasidone.