WO1998058924A1 - A process for the preparation of oxatomide - Google Patents

A process for the preparation of oxatomide Download PDF

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Publication number
WO1998058924A1
WO1998058924A1 PCT/EP1998/003770 EP9803770W WO9858924A1 WO 1998058924 A1 WO1998058924 A1 WO 1998058924A1 EP 9803770 W EP9803770 W EP 9803770W WO 9858924 A1 WO9858924 A1 WO 9858924A1
Authority
WO
WIPO (PCT)
Prior art keywords
oxatomide
alkali
formula
water
acid
Prior art date
Application number
PCT/EP1998/003770
Other languages
English (en)
French (fr)
Inventor
Leonardo Ambrosini
Carlo Bombarda
Original Assignee
Bidachem S.P.A.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bidachem S.P.A. filed Critical Bidachem S.P.A.
Priority to AU86282/98A priority Critical patent/AU8628298A/en
Publication of WO1998058924A1 publication Critical patent/WO1998058924A1/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Definitions

  • the present invention relates to a process for the preparation of oxatomide.
  • Oxatomide ( 1- [ 3- [ 4- ( diphenyl ethyl ) -1-piperazi- nyl]propyl]-l , 3-dihydro-2H-benzimidazol-2-one ) , is an anti-allergic and antiasthmatic known medicament.
  • the process for the preparation of oxatomide according to the invention comprises the following steps: a) reaction of i ⁇ opropen-2-yl benzimidazolone of formula (II) with a 3-halo-propyl-4-(diphenylme- thyl )piperazine salt of formula (III) in the presence of alkali and subsequent acid hydrolysis, to give oxatomide as a salt; b) transformation of (IV) into oxatomide free base (I) by means of alkali in water-organic solution.
  • X is a halogen, preferably chlorine .
  • Step a) is effected reacting isopropen-2-yl benzimidazolone (II) with a 3-halopropyl-(diphenylme- thyl )piperazine salt (III) in the presence of alkali and of a suitable organic solvent, at a temperature ranging from -10°C to 120°C; this condensation is followed by an acid hydrolysis to carry out the deprotection of the oxatomide isopropen-2-yl derivative (intermediate not isolated) thereby obtaining the salified oxatomide.
  • Compound of formula (III) is preferably 3- chloropropyl-( diphenylmethyl )piperazine dihydrochloride .
  • alkalis for activating the benzimidazolone derivative and for liberating piperazine free base from its salt (carried out in situ), are alkali or alkaline-earth hydroxides, alkali or alkaline- earth hydrides and alkali alkoxide ⁇ ;
  • suitable solvents are aromatic and aliphatic hydrocarbons, halogenated hydrocarbons, cyclic aliphatic ethers such as dioxolane and dioxane, alcohols, amides, water or mixtures thereof.
  • Step b) is effected treating compound (IV) in a suitable solvent in the presence of alkali.
  • suitable solvents are cyclic aliphatic ethers, such as dioxolane and dioxane, ketone ⁇ , alcohols, amides, water or mixtures thereof.
  • alkali are alkali or alkaline-earth carbonates or hydrogen carbonates, alkali or alkaline- earth hydroxides, organic amines such as triethyla ine , piperazine, alkali alkoxides, ammonia.
  • the process of the present invention is particularly convenient for use on industrial scale, in that the desired molecule is obtained in two only reaction steps, in a 70% process yield.
  • Oxatomide Oxatomide hydrochloride (10 g) was dissolved in a isopropanol-water 95:5 mixture (110 g) under reflux; a solution of potassium hydroxide (5 g) dissolved in an isopropanol-water 95:5 mixture (13.5 g) was added.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/EP1998/003770 1997-06-24 1998-06-19 A process for the preparation of oxatomide WO1998058924A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU86282/98A AU8628298A (en) 1997-06-24 1998-06-19 A process for the preparation of oxatomide

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT97MI001489A IT1292409B1 (it) 1997-06-24 1997-06-24 Procedimento per la preparazione di oxatomide
ITMI97A001489 1997-06-24

Publications (1)

Publication Number Publication Date
WO1998058924A1 true WO1998058924A1 (en) 1998-12-30

Family

ID=11377424

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1998/003770 WO1998058924A1 (en) 1997-06-24 1998-06-19 A process for the preparation of oxatomide

Country Status (3)

Country Link
AU (1) AU8628298A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
IT (1) IT1292409B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)
WO (1) WO1998058924A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113387893A (zh) * 2021-06-18 2021-09-14 山东汇海医药化工有限公司 一种奥沙米特的合成方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2714437A1 (de) * 1976-04-02 1977-10-20 Janssen Pharmaceutica Nv Piperazin- und piperidinderivate, verfahren zu ihrer herstellung und arzneipraeparate
DD299588A7 (de) * 1990-03-14 1992-04-30 Arzneimittelwerk Dresden Gmbh, Verfahren zur herstellung von 1-(3-(4-diphenylmethyl)-1-(piperazinyl)-propyl)-1.3-dihydro-2h-benzimidazol-2-on-hydrat

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2714437A1 (de) * 1976-04-02 1977-10-20 Janssen Pharmaceutica Nv Piperazin- und piperidinderivate, verfahren zu ihrer herstellung und arzneipraeparate
DD299588A7 (de) * 1990-03-14 1992-04-30 Arzneimittelwerk Dresden Gmbh, Verfahren zur herstellung von 1-(3-(4-diphenylmethyl)-1-(piperazinyl)-propyl)-1.3-dihydro-2h-benzimidazol-2-on-hydrat

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113387893A (zh) * 2021-06-18 2021-09-14 山东汇海医药化工有限公司 一种奥沙米特的合成方法

Also Published As

Publication number Publication date
ITMI971489A1 (it) 1998-12-24
IT1292409B1 (it) 1999-02-08
AU8628298A (en) 1999-01-04
ITMI971489A0 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1997-06-24

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