Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic 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
  • C07D401/02—Heterocyclic 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
  • C07D401/06—Heterocyclic 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.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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ID=11377424

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Cited By (1)

Citations (2)

• 1997
  • 1997-06-24 IT IT97MI001489A patent/IT1292409B1/it active IP Right Grant
• 1998
  • 1998-06-19 AU AU86282/98A patent/AU8628298A/en not_active Abandoned
  • 1998-06-19 WO PCT/EP1998/003770 patent/WO1998058924A1/en active Application Filing

Patent Citations (2)

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