Patent ID: 9409919
Filing Date: 2016-08-09
CPC Classification: B01J,C07D

Claim Text:
1. A process for the preparation of N-(2-((2R,12bS)-2′-oxo-1,3,4,6,7,12b-hexa-hydrospiro[benzofuro[2,3-a]quinolizine-2,4′-imidazolidine]-3′-yl)ethyl)-methane-sulfonamide, wherein the process comprises the following steps: in the first step (S)-1,3,4,6,7,12b-hexahydro-2H-benzo[b]furo[2,3-a]quinolizin-2-one of formula II: and N-(2-aminoethyl)methanesulfonamide of formula III: are contacted with trimethylsilyl cyanide in the presence of an agent capable of capturing water molecules, in an organic solvent, followed by adding hydrogen chloride to obtain (2R,12bS)-[2-[(cyano-1,3,4,6,7,12b-hexahydrobenzofuro-[2,3-a]quinolizine-2-yl)-amino]ethyl]methanesulfonamide dihydrochloride, in the second step (2R,12bS)-[2-[(cyano-1,3,4,6,7,12b-hexahydrobenzofuro-[2,3-a]quinolizine-2-yl)-amino]-ethyl]methanesulfonamide dihydrochloride is contacted with 1,1′-carbonyldiimidazole in the presence of a hydrogen chloride acceptor in an organic solvent to obtain (2R,12bS)-1,3,4,6,7,12b-hexahydro-[2,3-methylsulfonyl)-2-oxo-1-imidazolidinyl]-2H-benzo-furo[2,3-a]quinolizine-2-carbonitrile, and in the third step (2R,12bS)-1,3,4,6,7,12b-hexahydro-[2,3-methylsulfonyl)-2-oxo-1-imidazolidinyl]-2H-benzofuro[2,3-a]quinolizine-2-carbonitrile is contacted with hydrogen in the presence of Raney nickel catalyst and sodium methoxide or potassium tert-butoxide in methanol solvent to yield N-(2-((2R,12bS)-2′-oxo-1,3,4,6,7,12b-hexahydrospiro-[benzofuro[2,3-a]quinolizine-2,4′-imidazolidine]-3′-yl)ethyl)-methanesulfonamide.