Schering Corporation

Schering-plough Corporation

Martin Steinman

Yee-Shing Wong

Dinesh Gala

Pirouz Tahbaz

Ashit K Ganguly

Doris P Schumacher

Donald Hou

Guang-Zhong Wu

Xing Chen

Nicholas I Carruthers

Esther Babad

Yee S Wong

George G Wu

Allen Barnett

Ingrid Mergelsberg

William Billard

Brigitte Giesinger

Louis Iorio

Dominik Scherer

Pirouz Tabhaz

Gordon Crosby, Jr

The invention relates to intermediates of the formulae ##STR1## said intermediates being useful in a process for producing a compound of the formula ##STR2## wherein Bn is benzyl and R.sub.1, .sub.2 and R.sub.3 are as defined in the specification,

3-hydroxy gamma-lactone based enantioselective synthesis of azetidinones

Aminomethyl-phenylimidazoles are produced by reaction of an ester of a hydroxymethyl-phenylimidazole with an amine. A particularly preferred ester is the acetate ester. The aminomethyl-phenylimidazoles have useful properties as highly selective partial agonists or antagonists at brain dopamine receptor subtypes. A preferred compound prepared is 5-fluoro-2-�4-�(2-phenyl-1H-imidazol-5-yl)methyl!-1-piperazinyl!pyrimidine . Esters of the hydroxymethyl-phenylimidazoles are useful intermediates.

Preparation of aminomethyl-phenylimidazoles

The invention relates to a process for producing a compound of the formula ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined in the specification, which comprises the steps of: (a) reacting a lactone with an imine to obtain a chiral diol of the formula IV; (b) oxidizing the diol to obtain an aldehyde of formula V; (c) condensing the aldehyde with an enolether followed by dehydration to obtain a compound of formula VI; (d) hydrogenating the compound of formula VI to obtain a ketone of formula VII; and (e) chirally catalytically reducing the ketone, wherein steps (b)-(d) are shown in the following reaction scheme: ##STR2##

The invention relates to a process for producing the compound of the formula ##STR1## which comprises reacting lactone of formula II ##STR2## with an imine of formula III': ##STR3## and converting the resulting chiral diol of formula VI: ##STR4## through several steps to obtain a compound of formula I'.

3-hydroxy .gamma.-lactone based enantionselective synthesis of

Disclosed are a process and intermediates of the formulae ##STR1## wherein R is --CH.sub.2 OH or --OH and R.sup.3 is H or C.sub.1 -C.sub.6 alkyl; useful for preparing benzazepines of the formula ##STR2## having activity as selective D1 antangonists.

Process for preparing benzazepine intermediates for the synthesis of D1

The present invention relates to a process for preparing bicyclic compounds and intermediates thereof. The compounds are useful as anti-allergic, anti-inflammatory and/or cytoprotective agents.

Processes for preparing bicyclic compounds

The process for making certain bicyclic compounds and intermediates which are useful as anti-allergic, anti-inflammatory and cytoprotective agents.

Processes for preparing bicyclic compounds and intermediates thereof

There is disclosed a compound represented by the formula ##STR1## where P is a hydroxy protecting group.

Anhydro penicillin derivatives

There is disclosed an improved process for preparing albuterol which comprises reacting a 5-(haloacetyl)-2-hydroxybenzaldehyde with 1,1-dimethylethanamine in an organic solvent and in an inert atmosphere to form 5-[[(1,1-dimethylethyl)amino]acetyl]- 2-hydroxybenzaldehyde and reducing the carbonyl functions to the corresponding hydroxy groups to form albuterol.

Method for the preparation of .alpha..sup.1

The invention describes a method for determining the BZ-1 receptor activity of a test sample or a potential anxiolytic drug.

Method for measuring the BZ-1 receptor binding activity in a test sample

There is disclosed an improved process for preparing albuterol which comprises reacting a 5-(haloacetyl)-2-hydroxybenzaldehyde with 1,1-dimethylethanamine in an organic solvent and in an inert atmosphere to form 5-[[(1,1-dimethylethyl)amino]acetyl]-2-hydroxybenzaldehyde and reducing the carbonyl functions to the corresponding hydroxy groups to form albuterol.

Intermediates in the preparation of alpha1(((1,1-dimethylethyl) amino)

There is disclosed a compound represented by the formula ##STR1## wherein each P is hydrogen or a hydroxy protecting group and R and R' are each the same and are hydrogen, ##STR2## wherein R' is lower alkyl and R'' is a carboxy protecting group. The compounds are useful as intermediates for preparing penems.

Synthesis of azetidinones

Processes for preparing bicyclic compounds useful as anti-allergic, anti-inflammatory and/or cytoprotective agents are described, together with a process for preparing intermediates thereof.

Process for preparing intermediates for pharmaceutically useful bicyclic

A multi-step stereospecific process for preparing (3S,4R,5R)-1-(allyloxycarbonyl)-methyl-3-(1-hydroxyethyl)-4-beta-naphthoxy thi ocarbonylthio-2-azetidinone, stereoisomers thereof or hydroxy protected analogs thereof from anhydropenicillin. The azetidinones are intermediates useful for producing penems which are a known group or antibacterial compounds. The process involves protecting the hydroxy group of anhydropenicillin with a readily removable hydroxy protecting group, then reacting the resulting compound by treatment with oxygen and cuprous chloride in methanol, followed by reaction with ozone to produce a hydroxy protected dithiobis azetidinone and convert the methylidene groups originally in the 2-position of anhydropenicillin and in the bis-compound, to a (methoxycarbonyl)-carbonyl group. The resulting compound is converted to the unprotected dithiobis compound by reaction with ammonium hydroxide, then allyliodoacetate followed by an acid. Reaction of the resulting compound with zinc and a mineral acid followed by reaction with 0-2-naphthalenylcarbonochloridothioate converts the unprotected dithiobis compound to 1-(allyloxycarbonyl)methyl-3-(1-hydroxyethyl)-4-beta-naphthoxy (thiocarbonyl)thio-2-azetidinone.

Synthesis of azetidinones using CuCl

There is disclosed a high yielding process for cleaving penicillinates with acyl or aroyl nitrates to produce acyloxy or aroyloxy azetidinones which are intermediates in the multistep process for producing penems from penicillinates.

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Livingston, NJ, United States of America

Martin Steinman