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US 5,686,614 AGranted
Preparation of chiral 5-aminocarbonyl-5H-dibenzoa,d!cyclohepten-5,10-imines by optical resolution
AssigneeNeurogen Corporation
InventorsTappey H. Jones, Kenner C. Rice
Life of this patent
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Abstract
Disclosed are processes for resolving a racemic mixture of 5-aminocarbonyl-5H-dibenzoa,d!cyclohepten-5,10-imines into component enantiomers comprising recrystallizaton of diasteriomeric tartrate salts.
Claims12
A process for resolving a racemic mixture of 5-aminocarbonyl-5H-dibenzoa,d!cycloheptene-5,10-imines into its component enantiomers comprising selectively crystallizing a first diasteriomeric tartrate salt from a mixture of two diasteriomeric tartrate salts of the 5-aminocarbonyl-5H-dibenzoa,d!cycloheptene-5,10-imines in a mixture of ethanol and water,
- the 5-aminocarbonyl-5H-dibenzoa,d!cycloheptene-5,10-imines having the formula ##STR6## wherein wherein each of R.sub.1 and R.sub.2 is independently selected from hydrido, linear or branched alkyl groups of from one to twenty carbon atoms, alkenyl groups from two to twenty carbon atoms, alkynyl groups from two to twenty carbon atoms, cycloalkyl groups of three to eight carbon atoms, cycloalkenyl groups from three to eight carbon atoms, and wherein R.sub.1 and R.sub.2 may be taken together to form a N-containing cyclic structure having two to eight carbon atoms, any of the said groups being optionally substituted with one or more substituents selected from alkyl, haloalkyl, hydroxyalkyl, alkenyl, oxo, hydroxyl, alkoxy, thio, alkoxyalkyl, amino, halo, cyano or mercapto, and wherein R.sub.3 and R.sub.4 are independently selected from hydrido, linear or branched alkyl groups of from one to ten carbon atoms, alkenyl groups from two to ten carbon atoms, alkynyl groups from two to ten carbon atoms, hydroxyl, amino, alkylamino, alkoxy, cyano, nitro, haloalkyl and mercapto, and wherein R.sub.5 is selected from hydrido, linear or branched alkyl groups of from one to about ten carbon atoms, alkenyl groups from two to ten carbon atoms, alkynyl groups from two to about ten carbon atoms, hydroxyl, phenyl, haloalkyl, aminoalkyl, 1-phenylmethyl, 2-phenylethyl and alkoxy, and wherein R.sub.1 and R.sub.5 taken together form a cyclic structure containing two nitrogen atoms possessing from two to six carbon atoms, any of the said groups being optionally substituted by alkyl, oxo, thio, alkoxy, hydroxy, amino, alkylamino, phenyl, haloalkyl and thio.
A process for resolving a racemic mixture of 5-aminocarbonyl-5H-dibenzoa,d!cycloheptene-5,10-imines into its component enantiomers comprising
- (a) selectively crystallizing a first diasteriomeric tartrate salt from an ethanol and water solution of diasteriomeric tartrate salts of the 5-aminocarbonyl-5H-dibenzoa,d!cycloheptene-5,10-imines, the mixture of diasteriomeric tartrate salts being prepared using a first enantiomer of tartaric acid;
- (b) separating the first diasteriomeric tartrate salt from the solution and isolating a filtrate;
- and
- (c) forming a second diasteriomeric tartrate salt from material dissolved in the filtrate obtained in (b), the second diasteriomeric tartrate salt being prepared using a second enantiomer of tartaric acid:
- the 5-aminocarbonyl-5H-dibenzoa,d!cycloheptene-5,10-imines having the formula ##STR7## wherein each of R.sub.1 and R.sub.2 is independently selected from hydrido, linear or branched alkyl groups of from one to twenty carbon atoms, alkenyl groups from two to twenty carbon atoms, alkynyl groups from two to twenty carbon atoms, cycloalkyl groups of three to about eight carbon atoms, cycloalkenyl groups from three to eight carbon atoms, and wherein R.sub.1 and R.sub.2 may be taken together to form a N-containing cyclic structure having two to eight carbon atoms, any of the said groups being optionally substituted with one or more substituents selected from alkyl, haloalkyl, hydroxyalkyl, alkenyl, oxo, hydroxyl, alkoxy, thio, alkoxyalkyl, amino, halo, cyano or mercapto, and wherein R.sub.3 and R.sub.4 are independently selected from hydrido, linear or branched alkyl groups of from one to ten carbon atoms, alkenyl groups from two to ten carbon atoms, alkynyl groups from two to ten carbon atoms, hydroxyl, amino, alkylamino, alkoxy, cyano, nitro, haloalkyl and mercapto, and wherein R.sub.5 is selected from hydrido, linear or branched alkyl groups of from one to ten carbon atoms, alkenyl groups from two to ten carbon atoms, alkynyl groups from two to ten carbon atoms, hydroxyl, phenyl, haloalkyl, aminoalkyl, 1-phenylmethyl, 2-phenylethyl and alkoxy, and wherein R.sub.1 and R.sub.5 taken together form a cyclic structure containing two nitrogen atoms possessing from two to six carbon atoms, any of the said groups being optionally substituted by alkyl, oxo, thio, alkoxy, hydroxy, amino, alkylamino, phenyl, haloalkyl and thio.
2 more elements
Dependencies are inferred from the claim text.