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US 9,790,237 B2Granted
Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates
AssigneeJohnson Matthey Public Limited Company
InventorsDaniel J. Coughlin, Jeremy C. Wilt, Da-Ming Gou, Steven Collier
Life of this patent
Estimating the term…
Abstract
Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively wherein, R1 and R2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR3R4, OR5, or SR5, where R3 and R4 are individually selected from acyl or sulfonyl, and where R5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.
Claims1
A process for preparing lurasidone comprising the steps of:
- (i) alkylating (3aR,4S,7R,7aS)-hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione by reacting it with (5aR,9aR)-octahydrobenzo[e][1,3,2]dioxathiepine-3,3-dioxide in the presence of K2CO3 to form potassium ((1R,2R)-2-(((3aR,4S,7R,7aS)-1,3-dioxooctahydro-2H-4,7-methanoisoindol -2-yl)methyl)cyclohexyl)methyl sulfate;
- (ii) hydrolyzing potassium ((1R,2R)-2-(((3 aR,4S,7R,7 aS)-1,3 -dioxooctahydro-2H-4,7-methanoisoindol -2-yl)methyl)cyclohexyl)methyl sulfate to form (3aR,4S,7R,7aS)-2-(((1R,2R)-2-(hydroxymethyl) cyclohexyl)methyl) hexahydro-1H-4,7-methanoisoindole-1,3 (2H)-dione;
- (iii) reacting (3aR,4S,7R,7aS)-2-(((1R,2R)-2-(hydroxymethyl)cyclohexyl)methyl) hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione with methanesulfonyl chloride to form ((1R,2R)-2-(((3 aR,4S,7R,7aS)-1,3-dioxooctahydro-2H-4,7-methanoisoindol-2-yl) methyl)cyclohexyl)methyl methanesulfonate;
- and
- (iv) reacting 3-(piperazin-l-yl)benzo[d]isothiazole with ((1R,2R)-2-(((3aR,4S,7R,7aS)- 1,3-dioxooctahydro-2H-4,7-methanoisoindol-2-yl)methyl)cyclohexyl)methyl methanesulfonate to form (3 aR,4S,7R,7aS)-2(((1R,2R)-2-((4-(benzo[d]isothiazol-3-yl)piperazin-1- yl) methyl)cyclohexyl)methyl)hexahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (Lurasidone).
2 more elements
Dependencies are inferred from the claim text.