Farmabios S.p.a.

Euticals Prime European Therapeutical Spa

Claudio Gianluca Pozzoli

Valentina Canevari

Matteo Curti

Claudio Giordano

Maurizio Velati

Marco Brusasca

Cristina Manfrotto

Vincenzo Redaelli

Lorenzo Menna

Franco Malanga

Andrea Busca

Marco Nicolini

Fabio Benedetti

A method for the purification and preparation of melphalan that allows to obtain melphalan with purity higher than 99.5% is described.

Process for the purification of melphalan

A process for the preparation of nucleosides, derivatives and analogues thereof by coupling reaction of a protected suitable nitrogeneous purine or pyrimidine base, a derivative or analogue thereof and a protected suitable sugar in the presence of SnClcomprising the removal of SnCl4 by adding DMSO directly into the reaction mixture is described. Preferably said process is used for the preparation of antiviral and antitumor agents having a nucleoside or nucleoside-like structure, still more preferably for the preparation of azacytidine, decitabine, chlorfarabine, cladribine, mizoribine. A residual tin content lower than 300 ppm is obtained with said process.

Synthesis of nucleosides

A process for the preparation of neuromuscular blocking agents with isoquinoline structure, such as atracurium besylate, doxacurium chloride, mivacurium chloride and gantacurium chloride, by chromatographic purification of their mixtures of isomers using a silica modified by treatment with a tertiary amine of formula NRRRor a corresponding quaternary ammonium compound NRRRRXwherein R, R, Rand R, the same or different, are linear or branched C-Calkyl groups or &#x2014;CH&#x2014;Ar groups or two among R, R, Rand Rform a 5- or 6-membered cycle, optionally substituted with a &#x2014;CH&#x2014;Ar group or condensed with an Ar group, Ar being an aryl optionally substituted with one or more electrodonating groups, and Xbeing a suitable anion, is described.

Process for the purification of neuromuscular blocking agents

A process for preparing the [R&#x2014;[R*,R*-(E)]]-2,2'-(1,8-dioxo-4-octene-1,8-diyl) bis(oxy-3,1-propanediyl)bis(1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-[(3,4,5-trimethoxyphenyl) methyl]isoquinolinium) dichloride, commonly known as mivacurium chloride, useful as short-duration neuromuscular blocking agent.

Process for the preparation of mivacurium chloride

A process is described for the preparation of arylpyridine compounds by aryl-aryl cross-coupling reactions between a halopyridine and an arylmagnesium halide carried out in the presence of a catalytic amount of a zinc salt and a catalytic amount of palladium. The zinc salt is preferably selected from ZnCl , ZnBr and/or Zn(OAc) , while the palladium is preferably used in the form of Pd(PPh ) or Pd(OAc) &plus;4 PPh . The reaction can also be carried out in the presence of bidentate phosphines, such as, for example, 1,3-bis(diphenylphosphine)propane or 1,4-bis(diphenylphosphine)-butane. It is thus possible to obtain molar yields higher than 97% (calculated relative to the halopyridine) and a catalyticity of more than 2000.

Process for the preparation of aryl-pyridinyl compounds

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Monza, Italy

Claudio Gianluca Pozzoli