Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates

Patent metadata

Field	Value
Publication number	US-9790237-B2
Application number	US-201514737599-A
Country	US
Kind code	B2
Filing date	Jun 12, 2015
Priority date	Jun 16, 2014
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively

wherein, R 1 and R 2 are individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NR 3 R 4 , OR 5 , or SR 5 , where R 3 and R 4 are individually selected from acyl or sulfonyl, and where R 5 is aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

First claim

What is claimed is:

1. 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 K 2 CO 3 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).

Assignees

• Johnson Matthey Plc

Inventors

• Coughlin Daniel J
• Wilt Jeremy C
• Gou Da-Ming
• Collier Steven

Classifications

• C07D519/00 Primary

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D417/08

  linked by a carbon chain containing alicyclic rings · CPC title

• C07D471/12

  in which the condensed system contains three hetero rings · CPC title

• C07D261/20

  condensed with carbocyclic rings or ring systems · CPC title