G.d. Searle & Company

Pharmacia Corporation (of Pfizer, Inc.)

Thomas R Kowar

Joseph J Wieczorek

Richard M Weier

John S Ng

Bernhard Erb

Ping T Wang

Yuen-Lung L Sing

Leo J Letendre

Mark John Pozzo

Edward E Yonan

Chin Liu

Jon P Lawson

Dennis K Anderson

Sastry A Kunda

Julio A Baez

Mike G Scaros

John H Dygos

Kathleen T McLaughlin

Michael L Prunier

Gatis Plume

Richard J Salzmann

Intermediates in the preparation of 9,11-epoxy steroids are disclosed. Particularly, disclosed are 11,12-epoxy steroid, 4,5-9,11-diepoxy steroid and 12-keto steroid intermediates.

Processes for preparation of 9,11-epoxy steroids and intermediates useful therein

Processes for the preparation of 4,5-dihydro-5,7-lactone steroid compounds are provided.

Processes for preparation of 9, 11-epoxy steroids and intermediates useful therein

The present invention relates to a novel process for the preparation of N-heterocyclealkanamide derivatives having the following formula: ##STR1## which comprises reacting 1-(2-chloroethyl)piperidine with 2-chlorobenzeneacetonitrile to give (.+-.)-.alpha.-(2-chlorophenyl)-1-piperidinebutanenitrile; alkylating the piperidenebutanenitrile to give (.+-.)-.alpha.-(2-chlorophenyl)-.alpha.-(2,2-dimethoxyethyl)piperidine-1-b utanenitrile; hydrolyzing the resulting alkylated piperidinebutanenitrile to give (.+-.)-.alpha.-(2-chlorophenyl)-.alpha.-(2-oxoethyl)piperidine-1-butanenit rile; reacting the resulting piperidinebutanenitrile with isopropylamine to form (.+-.)-.alpha.-(2-chlorophenyl)-.alpha.-�2-�(1-methylethyl)imino!ethyl!pip eridine-1-butanenitrile; reducing the resulting imine to form (.+-.)-.alpha.-(2-chlorophenyl)-.alpha.-�2-�(1-methylethyl)amino!ethyl!-pi peridine-1-butanenitrile; acetylating the resulting amine to form (.+-.)-N-�3-(2-chlorophenyl)-3-cyano-5-(1-piperidinyl)pentyl!-N-(1-methyle thyl)acetamide; hydrolyzing the resulting acetylated amino substituted piperidine butanenitrile to form (.+-.)-.alpha.-�2-�acetyl(1-methylethyl)amino!ethyl!-.alpha.-(2-chlorophen yl)-1-piperidinebutanamide; and isolating the resulting piperidinebutanamide.

Process for the preparation of heterocyclic alkylamide derivatives

The present invention relates to a novel process for the preparation of heterocyclic alkylamide derivatives having the following formula: ##STR1## and the pharmaceutically acceptable acid addition salt thereof wherein X represents halo, alkyl having 1 to 6 carbon atoms, hydrido, trifluoromethyl, phenyl, or lower alkoxy having 1 to 6 carbon atoms; Y represents the group --CN or --CONH.sub.2 ; R.sub.2 represents alkyl having 1 to 6 carbon atoms; R.sub.3 represents acetyl, benzoyl, phenacetyl or trifluoroacetyl; m is the integer 1 or 2 and n is an integer from 1 to 3 inclusive; which comprises alkylating an aminoalkanol using a benzaldehyde/aminoalkanol/ketone mixture in the presence of a platinum catalyst to give an alkyl substituted phenylmethylaminoalkanol; halogenating the alkanol using a halogenating agent to give a haloalkyl alkylbenzenemethanamine salt; treating the salt with substituted phenyl piperidinealkanenitrile or substituted phenyl pyrrolidinealkanenitrile in the presence of base and dimethyl sulfoxide to give a substituted phenyl substituted aminoalkyl piperidinealkanenitrile or substituted aminoalkyl pyrrolidinealkanenitrile; hydration of the nitrile to give the corresponding amide; and N-debenzylation of the amide followed by acetylation to give the compounds of formula I wherein Y is --CONH.sub.2.

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Mt. Prospect, IL, United States of America

Thomas R Kowar