Patents Assigned to Procos S.p.A.
  • Patent number: 11459303
    Abstract: Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.
    Type: Grant
    Filed: June 19, 2020
    Date of Patent: October 4, 2022
    Assignee: Procos S.P.A.
    Inventors: Monica Donnola, Alessandro Barozza, Jacopo Roletto, Paolo Paissoni
  • Publication number: 20220251111
    Abstract: The present invention relates to a process for the preparation of an amorphous form of midostaurin with a low content of residual organic solvent.
    Type: Application
    Filed: August 5, 2020
    Publication date: August 11, 2022
    Applicant: Procos S.P.A.
    Inventors: Alberto Lena, Matteo Baudino, Gabriele Prina Cerai, Antonio Toppino, Jacopo Roletto, Paolo Paissoni
  • Publication number: 20220204455
    Abstract: Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.
    Type: Application
    Filed: June 19, 2020
    Publication date: June 30, 2022
    Applicant: Procos S.P.A.
    Inventors: Monica Donnola, Alessandro Barozza, Jacopo Roletto, Paolo Paissoni
  • Patent number: 11344550
    Abstract: The present invention concerns a process for the preparation of the crystalline form III of Tipiracil hydrochloride having a content of residual solvents lower than the ICH limits. Said process is advantageous with respect to the known processes because it allows the production of the form III of Tipiracil hydrochloride suitable for use in the preparation of pharmaceutical finished products.
    Type: Grant
    Filed: October 23, 2018
    Date of Patent: May 31, 2022
    Assignee: Procos S.P.A.
    Inventors: Fabio Morana, Stefano Gobbato, Lucia Cozzi, Jacopo Roletto, Paolo Paissoni
  • Publication number: 20220098170
    Abstract: Disclosed is a process for the synthesis of gepirone of formula (I) from 8-(pyrimidin-2-yl)-5,8-diazaspiro[4,5]decan-5-ium bromide. The process according to the invention is economically efficient and easily industrially scalable.
    Type: Application
    Filed: January 13, 2020
    Publication date: March 31, 2022
    Applicant: Procos S.P.A.
    Inventors: Giampiero Colombano, Mauro Barbero, Giovanni Battista Giovenzana, Jacopo Roletto, Paolo Paissoni
  • Patent number: 11286254
    Abstract: The present invention discloses a process for the preparation of 2-benzhydryl-3-quinuclidinone (1). (I). The process of the invention allows to obtain the intermediate 2-benzhydryl-3-quinuclidinone (1) by reaction of 2-benzylidene-3-quinuclidinone (2) with the Grignard reagent phenyl-magnesium halide, in particular chloride or bromide, in the presence of catalytic amounts of copper (I) salts. Taking advantage of the high efficiency of the catalytic system of the copper (I) salts, 2-benzhydryl-3-quinuclidinone (1) is obtained in higher yields than those of the known processes. Advantageously, since the amounts of copper (I) salts are catalytic, the latter can easily be removed from the reaction mixture, and the process is carried out in the presence of solvents less toxic and expensive than those used in the state of the art.
    Type: Grant
    Filed: October 30, 2018
    Date of Patent: March 29, 2022
    Assignee: Procos S.P.A.
    Inventors: Monica Donnola, Matteo Mossotti, Mauro Barbero, Jacopo Roletto, Paolo Paissoni
  • Patent number: 11028057
    Abstract: The invention relates to a process for the synthesis of 6-chloromethyluracil (6-(chloromethyl)pyrimidin-2,4(1H,3H)-dione) from ethyl 4-chloroacetoacetate and S-methylisothiourea hemisulfate via isolation of the novel intermediate 6-(chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one, and its subsequent treatment with aqueous sulfuric acid. Formula (I).
    Type: Grant
    Filed: February 13, 2019
    Date of Patent: June 8, 2021
    Assignee: Procos S.P.A.
    Inventors: Fabio Morana, Stefano Gobbato, Jacopo Roletto, Paolo Paissoni
  • Publication number: 20200407330
    Abstract: The invention relates to a process for the synthesis of 6-chloromethyluracil (6-(chloromethyl)pyrimidin-2,4(1H,3H)-dione) from ethyl 4-chloroacetoacetate and S-methylisothiourea hemisulfate via isolation of the novel intermediate 6-(chloromethyl)-6-hydroxy-2-(methylthio)-5,6-dihydropyrimidin-4(1H)-one, and its subsequent treatment with aqueous sulfuric acid. Formula (I).
    Type: Application
    Filed: February 13, 2019
    Publication date: December 31, 2020
    Applicant: Procos S.P.A.
    Inventors: Fabio Morana, Stefano Gobbato, Jacopo Roletto, Paolo Paissoni
  • Publication number: 20200339561
    Abstract: The present invention discloses a process for the preparation of 2-benzhydryl-3-quinuclidinone (1). (I). The process of the invention allows to obtain the intermediate 2-benzhydryl-3-quinuclidinone (1) by reaction of 2-benzylidene-3-quinuclidinone (2) with the Grignard reagent phenyl-magnesium halide, in particular chloride or bromide, in the presence of catalytic amounts of copper (I) salts. Taking advantage of the high efficiency of the catalytic system of the copper (I) salts, 2-benzhydryl-3-quinuclidinone (1) is obtained in higher yields than those of the known processes. Advantageously, since the amounts of copper (I) salts are catalytic, the latter can easily be removed from the reaction mixture, and the process is carried out in the presence of solvents less toxic and expensive than those used in the state of the art.
    Type: Application
    Filed: October 30, 2018
    Publication date: October 29, 2020
    Applicant: Procos S.P.A.
    Inventors: Monica Donnola, Matteo Mossotti, Mauro Barbero, Jacopo Roletto, Paolo Paissoni
  • Publication number: 20200330465
    Abstract: The present invention concerns a process for the preparation of the crystalline form III of Tipiracil hydrochloride having a content of residual solvents lower than the ICH limits. Said process is advantageous with respect to the known processes because it allows the production of the form III of Tipiracil hydrochloride suitable for use in the preparation of pharmaceutical finished products.
    Type: Application
    Filed: October 23, 2018
    Publication date: October 22, 2020
    Applicant: Procos S.P.A.
    Inventors: Fabio Morana, Stefano Gobbato, Lucia Cozzi, Jacopo Roletto, Paolo Paissoni
  • Patent number: 10626102
    Abstract: Disclosed is a process for the synthesis of efinaconazole (I), starting from 1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole and 4-methylenepiperidine, as free base or hydrochloride, in an organic solvent, under anhydrous conditions and in the presence of neutralising agents and reaction-promoting metal species. (1) The process is particularly advantageous because it gives rise to efinaconazole in high yields and purity, and uses little more than the stoichiometric amount of 4-methylenepiperidine, a rather expensive commercially available reagent.
    Type: Grant
    Filed: December 22, 2016
    Date of Patent: April 21, 2020
    Assignee: Procos S.P.A.
    Inventors: Martino Veronese, Piergiorgio Bettoni, Jacopo Roletto, Paolo Paissoni
  • Publication number: 20190010141
    Abstract: Disclosed is a process for the synthesis of efinaconazole (I), starting from 1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole and 4-methylenepiperidine, as free base or hydrochloride, in an organic solvent, under anhydrous conditions and in the presence of neutralising agents and reaction-promoting metal species. (1) The process is particularly advantageous because it gives rise to efinaconazole in high yields and purity, and uses little more than the stoichiometric amount of 4-methylenepiperidine, a rather expensive commercially available reagent.
    Type: Application
    Filed: December 22, 2016
    Publication date: January 10, 2019
    Applicant: Procos S.P.A.
    Inventors: Martino Veronese, Piergiorgio Bettoni, Jacopo Roletto, Paolo Paissoni
  • Patent number: 8877935
    Abstract: A process for the preparation of Dalfampridine (1), 4-aminopyridine, starting from 4-pyridinecarbonitrile using a one-pot procedure. Said process is carried out with no need for isolating intermediates and is particularly advantageous as far as environment, yields, productivity and purity of the resulting product are concerned, both in the reaction mixture and in the isolated crystal.
    Type: Grant
    Filed: June 7, 2011
    Date of Patent: November 4, 2014
    Assignee: Procos S.p.A.
    Inventors: Fabio Garavaglia, Alessandro Barozza, Jacopo Roletto, Paolo Paissoni
  • Patent number: 6521788
    Abstract: A process for the preparation of gabapentin of formula (I) which comprises: a) reduction of (1-nitromethyl-cyclohexyl)acetonitrile of formula (II)  to give 3-imino-2-aza-spiro[4.5]decan-2-ol of formula (III) b) transformation of compound (III), by alkali treatment, into 2-hydroxy-2-aza-spiro[4.5]decan-3-one of formula (IV) c) reduction of compound (IV) to give 2-aza-spiro[4.5]decan-3-one of formula (V) d) hydrolysis of compound (V) to gabapentin.
    Type: Grant
    Filed: May 29, 2002
    Date of Patent: February 18, 2003
    Assignee: Procos S.p.A.
    Inventors: Francesco Velardi, Mirco Fornaroli
  • Patent number: 6518456
    Abstract: A process for the production and purification of gabapentin, i.e. 1-(aminomethyl)cyclohexyl-acetic acid, which comprises hydrolysis of 2-aza-spiro[4.5]decan-3-one with HCl, treatment of the resulting product and filtration with acetone, dissolution in water at isoelectric pH and crystallization or digestion in the hot in mixtures of diisopropyl ether with ethanol or methanol.
    Type: Grant
    Filed: June 14, 2002
    Date of Patent: February 11, 2003
    Assignee: Procos S.p.A.
    Inventors: Diego Peverali, Mirco Fornaroli, Francesco Velardi