Sepracor, Inc.

Yaping Hong

Roger P Bakale

Charles M Zepp

Yun Gao

Chris Hugh Senanayake

Chrisantha Hugh Senanayake

Thomas P Jerussi

Paul D Rubin

John R McCullough

Gerald J Tanoury

Patrick Koch

Xiaoyi Nie

Fran A McConville

Richard R Feinberg

Tingjian Xiang

Martin P Redmon

Kostas Saranteas

Stephen Alan Wald

Fran A Mcconville

The invention is directed to compositions comprising, and methods of using, racemic N-desmethylzopiclone, optically pure (+)-N-desmethylzopiclone, and optically pure (&#x2212;)-N-desmethylzopiclone in the treatment and prevention of diseases and conditions in mammals. The invention is further directed to novel methods of preparing N-desmethylzopiclone, optically pure (+)-N-desmethylzopiclone, and optically pure (&#x2212;)-N-desmethylzopiclone.

Methods of treating and preventing a convulsive state

Polymorphic crystalline forms of the antihistaminic drug norasternizole are disclosed. Processes for the production of the preferred polymorph are also disclosed.

Norastemizole polymorphs

The invention is directed to compositions comprising, and methods of using, racemic N-desmethylzopiclone, optically pure (&plus;)-N-desmethylzopiclone, and optically pure (&minus;)-N-desmethylzopiclone in the treatment and prevention of diseases and conditions in mammals. The invention is further directed to novel methods of preparing N-desmethylzopiclone, optically pure (&plus;)-N-desmethylzopiclone, and optically pure (&minus;)-N-desmethylzopiclone.

Methods of making and using N-desmethylzopiclone

Methods of treating muscle spasms using N-desmethylzopiclone

A method of preparation of optically pure isomers of hydroxyitraconazole, in particular the two cis dioxolane diastereomers of the sec-butyl (S,S)-isomer, and to phosphate and sulfate derivatives thereof is disclosed. Pharmaceutical compositions containing these compounds and to their use for the treatment of fungal infection are also disclosed.

2R,4S,S,S- and 2S,4R,S,S-hydroxyitraconazole

A method of preparation of optically pure isomers of hydroxyitraconazole, in particular the two cis dioxolane diastereomers of the sec-butyl (R,S)-isomer, and to phosphate and sulfate derivatives thereof is disclosed. Pharmaceutical compositions containing these compounds and their use for the treatment of fungal infection are also disclosed.

2R, 4S, R, S- and 2S, 4R, R, S-hydroxyitraconazole

A method of preparation of optically pure isomers of hydroxyitraconazole, in particular the two cis dioxolane diastereomers of the sec-butyl (R,S)-isomer, and to phosphate and sulfate derivatives thereof is disclosed. Pharmaceutical compositions containing these compounds and to their use for the treatment of fungal infection are also disclosed.

2R,4S,R, S-  and 2S,4R,R,S-hydroxyitraconazole

The present invention is a method of preparing 2-substituted imidazoles from readily available imidazoles having a leaving group in the 2-position, by alkylating the imidazole under mild conditions to afford a 3-N-alkylated imidazolium salt; and coupling the imidazolium salt with a nucleophile also under mild conditions to afford a 2-substituted 3-N-alkylated imidazolium salt. The reaction product can optionally be isolated and purified. The 2-substituted 3-N-alkylated imidazolium salt is hydrolyzed to afford a 2-substituted imidazole. Alternatively, the imidazole is coupled with a nucleophile in the presence of fluoride ion to provide a 2-substituted imidazole.

Method for synthesizing 2-substituted imidazoles

A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed, as are the novel, substantially optically pure 1-amino-2-indanols and 1-amido-2-indanols obtained thereby. A preferred process converts indene to cis-1-amino-2-indanol.

Optically pure 1-amino-2-indanols

A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed. Novel, optically active 1-amido-2-indanols and 1-amino-2-alkanols are also disclosed.

Optically pure 1-amido-2-indanols

A two-step process for the conversion of a trans-1-amino-2-hydroxycycloalkane stereoselectively to a cis-1-amino-2-hydroxycycloalkane is disclosed. The novel step, a one-step hydrolysis with formal inversion, can be used to convert an amide of a trans-1-amino-2-hydroxycycloalkane to a cis-1-amino-2-hydroxycycloalkane. Methods for obtaining the trans-1-amino-2-hydroxycycloalkanes and their amides from alkenes are also disclosed. A preferred process converts indene to cis-1-amino-2-indanol.

Process for preparing cyclic CIS-1-amino-2-alkanols

A method for the enantioselective reduction of prochiral ketones using catalytic amounts of tetrahydroindeno[1,2-d][1,3,2] oxazaboroles of formula II is disclosed. ##STR1## The oxazaboroles can be generated in situ from the corresponding cis-1-amino-2-indanols or imino indanols (III) ##STR2## Novel compounds of formulas II and III are also disclosed.

Tetrahydroindeno[1,2-D][1,3,2]oxazaboroles and their use as

A method for the enantioselective reduction of an .alpha.-iminoketone to an .alpha.-aminoalcohol is disclosed. The method utilizes a borane reducing agent as the reducing agent and a chiral 1,3,2-oxazaborole as the catalyst. The method is applied to the synthesis of R-albuterol from methyl 5-acetylsalicylate in high yield and high optical purity.

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Framingham, MA, United States of America

Yaping Hong