Process for preparing 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3A,4,5,6-hexahydro-1H-benz de!isoqui nolin-1-one
AssigneeSyntex (U.S.A.) Inc.
InventorsJames Robinson, III, John C. Rohloff, Bruce A. Kowalczyk
Life of this patent
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Abstract
This invention relates to a process for preparing 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-tetrahydro-1H-benz de!isoquin olin-1-one, particularly 2-(1-azabicyclo 2.2.2!oct-3S-yl)-2,3,3aS,4,5,6-tetrahydro-1H-benz de!isoqu inolin-1-one, and to intermediates useful in such process.
Claims8
A process for preparing 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one and the pharmaceutically acceptable salts, individual stereoisomers and mixture of stereoisomers thereof, which process comprises:
- (A) reacting a compound of Formula 5:
- ##STR5## in which L is a leaving group, with 1-azabicyclo 2.2.2!oct-3-ylamine to give N-(1-azabicyclo 2.2.2!oct-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ylcarboxami de;
- (B) reducing the N-(1-azabicyclo 2.2.2!oct-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ylcarboxami de to give (1-azabicyclo 2.2.2!oct-3-yl)-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)ami ne;
- (C) reacting the (1-azabicyclo 2.2.2!oct-3-yl)(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)amin e with a formylating agent and then treating with a Lewis acid to give 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one;
- and
- (D) optionally separating a diastereomeric mixture of the 2H -(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquinol in-1-one into individual stereoisomers or mixtures of stereoisomers;
- (E) optionally converting the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one to a pharmaceutically acceptable acid addition salt;
- and
- (F) optionally converting an acid addition salt of the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one to non-salt form.
A process for preparing 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one and the pharmaceutically acceptable salts, individual stereoisomers and mixture of stereoisomers thereof, which process comprises:
- (A) reducing N-(1-azabicyclo 2.2.2!oct-3-yl)-1,2,3,4-tetrahydronaphthalen-1-ylcarboxami de to give (1-azabicyclo 2.2.2!oct-3-yl)-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)ami ne;
- (B) reacting the (1-azabicyclo 2.2.2!oct-3-yl)(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)amin e with a formylating agent and then treating with a Lewis acid to give 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one;
- and
- (C) optionally separating a diastereomeric mixture of the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one into individual stereoisomers or mixtures of stereoisomers;
- (D) optionally converting the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one to a pharmaceutically acceptable acid addition salt;
- and
- (E) optionally converting an acid addition salt of the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one to non-salt form.
A process for preparing 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one and the pharmaceutically acceptable salts, individual stereoisomers and mixture of stereoisomers thereof, which process comprises:
- (A) reacting (1-azabicyclo 2.2.2!oct-3-yl)(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)amin e with a formylating agent and then treating with a Lewis acid to give 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one;
- and
- (B) optionally separating a diastereomeric mixture of the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one into individual stereoisomers or mixtures of stereoisomers;
- (C) optionally converting the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one to a pharmaceutically acceptable acid addition salt;
- and
- (D) optionally converting an acid addition salt of the 2-(1-azabicyclo 2.2.2!oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz de!isoquino lin-1-one to non-salt form.
Dependencies are inferred from the claim text.