Teva Pharmaceutical Fine Chemicals S.r.l.

Teva Pharmaceutical Industries Limited

Teva Gyogyszergyar Zartkoruen Mukodo Reszvenytarsasag

Icrom S.p.a.

Teva Pharmaceutical Fine Chemicals

Paola Daverio

Stefano Bianchi

Silvia Mantovani

Eugenio Castelli

Judith Aronhime

Adrienne Kovacsne-Mezei

Valeriano Merli

Alessandra Vailati

Paolo Riva

Giuseppe Lo Monaco

Merli Valeriano

Angelo Spreafico

Augusto Canavesi

Matteo Colombo

Stella Borrelli

A process for the preparation of diaminophenothiazinium compounds is described, which allows achieving quickly and effectively a high degree of purity of the same.

Process for the preparation of diaminophenothiazinium compounds having a high degree of purity

The present invention provides improved processes for the preparation of atomoxetine hydrochloride under reaction conditions that improve reaction yields and facilitate commercial synthesis. In particular, the invention is directed to the synthesis of atomoxetine HCl by adding HCl to a mixture of (R)-(&#x2212;)-tomoxetine (S)-(+)-mandelate with an organic solvent, with or without a base and water.

Process for the preparation of atomoxetine hydrochloride

The invention is directed to levalbuterol HCl Form B and methods of making the same.

Levalbuterol hydrochloride polymorph B

Provided are processes for the preparation of (R)-SLB.D-DBTA salt and levalbuterol hydrochloride. Also provided are levalbuterol hydrochloride degradation products and processes for preparing them. Pharmaceutical compositions comprising at least one levalbuterol hydrochloride of the invention and at least one pharmaceutically-acceptable excipient are also provided.

Enantiomerically pure (R)-albuterol dibenzoyltartrate and protected analogs thereof

The present invention provides novel crystalline polymorph forms of atomoxetine hydrochloride denominated Forms B and C and methods for their preparation, as well as methods for the preparation of Form A. The present invention provides pharmaceutical compositions that comprise atomoxetine hydrochloride Form B, Form C, or mixtures thereof that can be used to treat attention deficit/hyperactivity disorder.

Polymorphs of atomoxetine hydrochloride

The invention is directed to processes for making levalbuterol HCl Polymorph A from by suspending or forming a first slurry of (R)-SLB(D)-DBTA in at least a first organic solvent, adding HCl to the suspension or slurry of the solid (R)-SLB.D-DBTA until the (R)-SLB.D-DBTA forms levalbuterol HCl Polymorph A, and isolating the levalbuterol HCl Polymorph A.

Levalbuterol hydrochloride Polymorph A

A crystalline Form II of memantine hydrochloride, pharmaceutical compositions containing crystalline Form II, and methods of preparing crystalline Forms I and II of memantine hydrochloride are provided.

Polymorphs of memantine hydrochloride

The invention encompasses processes for the preparation of darifenacin hydrobromide.

Processes for preparing darifenacin hydrobromide

The present invention provides enantiomerically pure (R)-(&#x2212;)-tomoxetine (S)-(+)-mandelate and atomoxetine HCl. The present invention further provides enantiomerically pure (R)-(&#x2212;)-tomoxetine (S)-(+)-mandelate prepared from racemic tomoxetine. The present invention also provides enantiomerically pure atomoxetine HCl prepared from (R)-(&#x2212;)-tomoxetine (S)-(+)-mandelate.

Enantiomerically pure atomoxetine and tomoxetine mandelate

The present invention provides improved processes for the preparation of atomoxetine hydrochloride under reaction conditions that improve reaction yields and facilitate commercial synthesis. In particular, the invention is directed to the synthesis of atomoxetine HCl by adding HCl to a mixture of (R)-(&#x2212;)-tomoxetine (S)-(+)-mandelate with an organic solvent, with or without a base and water. In preferred embodiments, the atomoxetine hydrochloride produced is Form A.

Processes for the preparation of atomoxetine hydrochloride

Provided are processes for preparing tomoxetine comprising reacting N-methyl-3-hydroxy-3-phenylpropylamine with dimethylsulfoxide (DMSO) and 2-fluorotoluene in the presence of an alkali base to form tomoxetine. Also provided is the conversion of said tomoxetine into atomoxetine or a pharmaceutically acceptable salt thereof.

Processes for the preparation of tomoxetine

The present invention provides a process for the optical resolution of racemic tomoxetine under reaction conditions that improve reaction yields and optical purity. The invention also provides an epimerization process for the (S)-(+) enantiomer. The invention further provides the conversion of the enantiomer obtained from the optical resolution into atomoxetine or a pharmaceutically acceptable salt thereof.

Process for the optical resolution and recycling of tomoxetine

Processes for separation of enantiomers of clopidogrel, and converting one enantiomer of clopidogrel to another enantiomer of clopidogrel are provided. The enantiomers are separated by crystallizing the (S) enantiomer as camphor sulfonate salt from a hydrocarbon, or a mixture of a hydrocarbon and a co-solvent, preferably DMF:toluene. The (R) enantiomer is then racemized and recycled by reaction with a catalytic amount of a base, preferably with t-butoxide.

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Milan, Italy

Paola Daverio