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US 5,665,878 AGranted
Stereoselective process for producing dihydro-2,3-benzodiazepine derivatives
AssigneeEli Lilly and Company
InventorsBenjamin A. Anderson, Marvin M. Hansen, David L. Varie, Jeffrey T. Vicenzi, Milton J. Zmijewski
Life of this patent
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Abstract
A process for stereoselectively forming N-substituted dihydro-2,3 benzodiazepines which are useful as AMPA receptor antagonists. The process includes an opening reduction step which sets the stereochemistry of the intermediates and the final compounds to the desired enantiomer. The reduction step may be carried out by an enzymatic reduction.
Claims25
A process for preparing a compound having the general formula:
- ##STR17## wherein R Aryl represents an unsubstituted or substituted aryl group is hydrogen or C.sub.1 -C.sub.10 alkyl;
- and
- X is hydrogen, C.sub.1 -C.sub.10 alkyl, acyl, aryl or carboxyl, or a substituted derivative thereof;
- said process comprising the steps of:
- a) providing a quantity of a compound having the formula:
- ##STR18## b) asymmetrically reducing the compound of formula II to yield a compound having the formula:
- ##STR19## c) reacting the compound of formula III with an arylaldehyde compound of formula Aryl.CHO to yield an isochroman compound having the formula:
- ##STR20## d) reacting the compound of formula IV with an oxidizing agent to yield a compound of the formula:
- ##STR21## e) reacting the compound of formula V with a hydrazide derivative of formula H.sub.2 NNHX to yield a compound of the formula:
- ##STR22## f) reacting the compound of formula VI with a (i) sulfonyl halide reagent and a base, to form an intermediate sulfonate;
- or (ii) by direct Mitsunobu cyclization to yield the compound of formula I.
8 more elements
A process for preparing a compound having the general formula:
- ##STR25## wherein R is hydrogen or a C.sub.1 -C.sub.10 alkyl;
- Aryl represents an unsubstituted or substituted aryl group;
- and
- X is hydrogen, C.sub.1 -C.sub.10 alkyl, acyl, aryl, carboxyl or a substituted derivative thereof, or a protecting group, or a pharmaceutically acceptable salt thereof, said process comprising cyclising a compound having the general formula ##STR26## wherein Z represents a leaving atom or group to afford a compound having the general formula I, whereafter, if desired, forming a pharmaceutically acceptable salt.
1 more element
Dependencies are inferred from the claim text.