公开(公告)号：US11286254B2

公开(公告)日：2022-03-29

申请号：US16760324

申请日：2018-10-30

Applicant: Procos S.P.A.

Inventor： Monica Donnola ,  Matteo Mossotti ,  Mauro Barbero ,  Jacopo Roletto ,  Paolo Paissoni

IPC: C07D453/02

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.

公开(公告)号：US20190010141A1

公开(公告)日：2019-01-10

申请号：US16066328

申请日：2016-12-22

Applicant: Procos S.P.A.

Inventor： Martino Veronese ,  Piergiorgio Bettoni ,  Jacopo Roletto ,  Paolo Paissoni

IPC: C07D401/06

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.

公开(公告)号：US20030009055A1

公开(公告)日：2003-01-09

申请号：US10156059

申请日：2002-05-29

Applicant: PROCOS S.P.A

Inventor： Francesco Velardi ,  Mirco Fornaroli

IPC: C07C227/22 ,  C07D209/54

CPC classification number: C07D209/54 ,  C07C227/12 ,  C07C227/22 ,  C07C2601/14

Abstract: A process for the preparation of gabapentin of formula (I) 1 which comprises: a) reduction of (1-nitromethyl-cyclohexyl)acetonitrile of formula (II) 2 to give 3-imino-2-aza-spironull4.5nulldecan-2-ol of formula (III) 3 b) transformation of compound (III), by alkali treatment, into 2-hydroxy-2-aza-spironull4.5nulldecan-3-one of formula (IV) 4 c) reduction of compound (IV) to give 2-aza-spironull4.5nulldecan-3-one of 5 d) hydrolysis of compound (V) to gabapentin.

Abstract translation: 制备式（I）的加巴喷丁的方法，其包括：a）还原式（II）的（1-硝基甲基 - 环己基）乙腈，得到3-亚氨基-2-氮杂 - 螺[4.5]癸-2-酮 式（Ⅳ）的二醇b）通过碱处理将化合物（Ⅲ）转变成式（Ⅳ）的2-羟基-2-氮杂 - 螺[4.5]癸烷-3-酮c）化合物（Ⅳ）的还原 得到d）将化合物（V）水解成加巴喷丁的2-氮杂 - 螺[4.5]癸烷-3-酮。

公开(公告)号：WO2022153263A1

公开(公告)日：2022-07-21

申请号：PCT/IB2022/050347

申请日：2022-01-17

Applicant: PROCOS S.P.A.

Inventor： VERONESE, Martino ,  BAROZZA, Alessandro ,  BETTONI, Piergiorgio ,  ROLETTO, Jacopo ,  PAISSONI, Paolo

IPC: C07D233/72 ,  C07D233/88

Abstract: Disclosed is a process for the synthesis of imepitoin of formula (I) by reacting 4- chloroaniline, chloroacetic acid and urea in the presence of an apolar or weakly polar aprotic solvent such as xylene, and then reacting the resulting 1-(4- chlorophenyl)imidazolidine-2, 4-dione (II) with morpholine in the presence of morpholine hydrochloride. Crystallisation from dimethyl sulphoxide and methanol provides pure imepitoin (I). The process is cheaper and more easily industrially scalable than the known procedures, thus enabling imepitoin to be produced with high yields and limited costs.

公开(公告)号：WO2021024202A1

公开(公告)日：2021-02-11

申请号：PCT/IB2020/057404

申请日：2020-08-05

Applicant: PROCOS S.P.A.

Inventor： LENA, Alberto ,  BAUDINO, Matteo ,  PRINA CERAI, Gabriele ,  TOPPINO, Antonio ,  ROLETTO, Jacopo ,  PAISSONI, Paolo

IPC: C07D498/22 ,  A61K31/553 ,  A61P35/00

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.

公开(公告)号：WO2019086434A1

公开(公告)日：2019-05-09

申请号：PCT/EP2018/079675

申请日：2018-10-30

Applicant: PROCOS S.P.A.

Inventor： DONNOLA, Monica ,  MOSSOTTI, Matteo ,  BARBERO, Mauro ,  ROLETTO, Jacopo ,  PAISSONI, Paolo

IPC: C07D453/02

CPC classification number: C07D453/02

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 phenylmagnesium 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.

公开(公告)号：WO2019086292A1

公开(公告)日：2019-05-09

申请号：PCT/EP2018/078964

申请日：2018-10-23

Applicant: PROCOS S.P.A.

Inventor： MORANA, Fabio ,  GOBBATO, Stefano ,  COZZI, Lucia ,  ROLETTO, Jacopo ,  PAISSONI, Paolo

IPC: C07D403/06 ,  A61K31/506 ,  A61P35/00

Abstract: PROCESS FOR THE PREPARATION OF THE CRYSTALLINE FORM III OF TIPIRACIL HYDROCHLORIDE 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.

公开(公告)号：WO2017072216A1

公开(公告)日：2017-05-04

申请号：PCT/EP2016/075899

申请日：2016-10-27

Applicant: PROCOS S.p.A.

Inventor： MOSSOTTI, Matteo ,  BAROZZA, Alessandro ,  ROLETTO, Jacopo ,  PAISSONI, Paolo

IPC: C07D213/64

CPC classification number: C07D213/64

Abstract: Disclosed is a process for the synthesis of Pirfenidone (1) from 5-methyl- 2(1H)-pyridinone and chlorobenzene in the presence of a catalytic system consisting of a copper salt and an organic ligand, in thepresence of a base. The process exploits the high efficiency of the catalytic system consisting of copper(I) salt and an organic ligandin the presence of an inorganic base in the N-amidation reaction of chlorobenzene, a cheap reagent also usable as solvent in this case; reaction conditions at high temperatures, at atmosphere pressureor higher, produce a reaction with good yields.

Abstract translation: 公开了一种由5-甲基-2（1H） - 吡啶酮和氯苯在由铜盐和有机配体组成的催化体系存在下合成吡非尼酮（1）的方法， 在一个基地的存在。 该方法利用在氯苯的N-酰胺化反应中存在无机碱的情况下由铜（I）盐和有机配体组成的催化体系的高效率，在这种情况下，廉价试剂也可用作溶剂; 在高温下，在大气压力或更高温度下的反应条件，产生良好收率的反应。

公开(公告)号：WO2015056205A1

公开(公告)日：2015-04-23

申请号：PCT/IB2014/065361

申请日：2014-10-16

Applicant: PROCOS S.P.A.

Inventor： ANGELINI, Tommaso ,  BETTONI, Piergiorgio ,  ROLETTO, Jacopo ,  PAISSONI, Paolo

IPC: C07D417/12

CPC classification number: C07D417/12

Abstract: Disclosed is a process for the industrial synthesis of Lurasidone from (1R,2R)-cyclohexane-1,2-diyldimethanol (1), 3-(piperazin-1- yl)benzo[d]isothiazole (3) and (3aR,4R,7R,7aS)-3a,4,7,7a-tetrahydro-4,7- methanoisobenzofuran-1,3-dione (6).). Said process is optimised to obtain Lurasidone with high yields and high purities by preparing highly pure synthesis intermediates, using critical raw materials and reagents in amounts close to the stoichiometric amounts, increasing productivity and reducing the costs and environmental impact of the process.

Abstract translation: 公开了从（1R，2R） - 环己烷-1,2-二基二甲醇（1），3-（哌嗪-1-基）苯并[d]异噻唑（3）和（3aR，4R）的工业合成卢拉西酮的方法 ，7R，7aS）-3a，4,7,7a-四氢-4,7-甲烷异苯并呋喃-1,3-二酮（6））。 所述方法被优化以通过制备高纯度的合成中间体来获得具有高产率和高纯度的Lurasidone，使用临近的原料和试剂，其量接近化学计量量，提高生产率并降低该方法的成本和环境影响。

公开(公告)号：WO2020254580A1

公开(公告)日：2020-12-24

申请号：PCT/EP2020/067105

申请日：2020-06-19

Applicant: PROCOS S.P.A.

Inventor： DONNOLA, Monica ,  BAROZZA, Alessandro ,  ROLETTO, Jacopo ,  PAISSONI, Paolo

IPC: C07D233/22 ,  A61K31/415

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.