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.

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.

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.

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.

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.

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.