CH510647A - Sulphonamides and process for the manufacture thereof - Google Patents

Sulphonamides and process for the manufacture thereof

Info

Publication number
CH510647A
CH510647A CH787169A CH787169A CH510647A CH 510647 A CH510647 A CH 510647A CH 787169 A CH787169 A CH 787169A CH 787169 A CH787169 A CH 787169A CH 510647 A CH510647 A CH 510647A
Authority
CH
Switzerland
Prior art keywords
amino
aminocyclohexanol
formula
trans
halogen
Prior art date
Application number
CH787169A
Other languages
German (de)
Inventor
Bretschneider Hermann Dr Prof
Helmut Dr Egg
Peter Dr Quitt
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Priority to CH787169A priority Critical patent/CH510647A/en
Priority claimed from CH1136566A external-priority patent/CH500176A/en
Priority claimed from CH787569A external-priority patent/CH509992A/en
Publication of CH510647A publication Critical patent/CH510647A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/52—Y being a hetero atom
    • C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
    • C07C311/57—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/59—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea having sulfur atoms of the sulfonylurea groups bound to carbon atoms of six-membered aromatic rings having nitrogen atoms of the sulfonylurea groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/28—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

(A) Cpds. of the formulae:- (I) R1 = H R2 = OH, or together with R' = keto R3 = phenyl opt. subst. by one or more halogen, lower alkyl, lower alkoxy, lower alkylthio, acetyl, amino, acylamino, diacylimido, or lower alkoxy and/or halogen substd. benzamidoethyl; 5-6 membered nitrogen heterocycle attached by the nitrogen atom n = 3 or 4. (B) N-(p-Chlorobenzenesulphonyl)-3,5-dimethyl-1-pyrazole carboxamide. Cpds. I and VI have blood-sugar depressing activity.

Description

  

  
 



  Verfahren zur Herstellung von Sulfonamiden
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von   Sulfony]harnstoffderivaten    der Formel I
EMI1.1     
 in der R Phenyl, das durch Halogen, Niederalkyl-, Niederalkoxy-, Niederalkylthio-, Acetyl-, Amino-, Acylamino- oder Diacylimidogruppen substituiert sein kann, und n die Zahl 3 oder 4 bedeutet.



   Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man eine Verbindung der Formel  ][i[
EMI1.2     
 mit   2-Aminocyclohexanol    bzw. cyclopentanol, zweckmässig mit einem Moläquivalent davon, behandelt.



   Unter niederen Alkylgruppen, die in durch das Sym   bol    R repräsentierten Resten enthalten sind, sollen gerad   kettige    oder verzweigte Alkylgruppen mit 1-6 Kohlenstoffatomen verstanden werden. Beispiele dafür sind Methyl, Äthyl, Propyl, Tsopropyl, Butyl, Pentyl, Hexyl und deren Isomeren. Ein durch das Symbol R dargestelltes Halogenphenyl ist vorzugsweise Chlorphenyl. Eine durch das Symbol R dargestellte Acylaminophenylgruppe kann   aliphatische    oder aromatische Acylreste enthalten. Bei spiele für solche Gruppen sind Acetaminophenyl oder Benzoylaminophenyl. Eine Diacylimidophenylgruppe ist beispielsweise die Phthalimidophenylgruppe.



   Die Ausgangsstoffe der Formel II können in Analogie zu der im nachstehenden Beispiel beschriebenen Verfahrensweise hergestellt werden (vgl. auch die belgische   Pa-      tentsehrift    Nr. 702 280).



   Die erfindungsgemäss erhältlichen Verbindungen der allgemeinen Formel   1    zeichnen sich durch eine aussergewöhnliche blutzuckersenkende Aktivität bei oraler Applikation aus. Die Verbindungen haben eine kurze Verweilzeit im Organismus und werden weitgehend unver ändert ausgeschieden. Sie können daher als Heilmittel in Form pharmazeutischer Präparate Verwendung finden, welche sie in Mischung mit einem geeigneten pharmazeutischen, organischen oder anorganischen inerten Träger   material    enthalten.



   Beispiel
2,55 g O,N-Bis-Tosylcarbamoyl-trans-2-aminocyclohexanol und 0,8 g   trans-2-Aminocyclohexanol    werden mit 2 ml abs. Pyridin 4 Stunden auf 1200 C erhitzt. Das Reaktionsprodukt wird nach dem Erkalten mit 20 ml 1 n NaOH versetzt. Nach Filtration wird die Lösung mit   CO    gesättigt, nochmals filtriert und mit 2 n Salzsäure angesäuert. Der   l-(p-Toluolsulfonyl)-3-(trans-2-hydroxy-      cyclohexyl)-harn stoff    kristallisiert beim Stehen.



   Das Ausgangsmaterial kann wie folgt hergestellt werden:
Zu einer Lösung von 5,75 g trans-2-Amino-cyclohexanol in 50 ml abs. Dimethylformamid wird nach Zugabe von 7,5 ml Triäthylamin langsam unter Eiskühlung und Rühren 17 ml p-Toluolsulfonylisocyanat getropft. Nach 2tägigem Stehen bei Raumtemperatur wird das Lösungsmittel   verdampft    und der Rückstand in 50 ml 2 n NaOH gelöst. Beim Sättigen der Lösung mit   CO    scheidet sich ein braunes Harz ab, von dem abdekantiert wird. Nach erschöpfender Ätherextraktion wird die wässrige Lösung mit 2n Salzsäure angesäuert. Das sich dabei abscheidende ölige   O,N-Bis-Tosylcarbamoyl-trans-2-aminocyclo-    hexanol kristallisiert beim Stehen. 

  Schmelzpunkt nach Umfällen aus verdünnter Natronlauge und   Umkristallit    sieren aus Alkohol   200-2050    C. 



  
 



  Process for the preparation of sulfonamides
The present invention relates to a process for the preparation of sulfonyl urea derivatives of the formula I.
EMI1.1
 in which R is phenyl, which can be substituted by halogen, lower alkyl, lower alkoxy, lower alkylthio, acetyl, amino, acylamino or diacylimido groups, and n is the number 3 or 4.



   The process according to the invention is characterized in that a compound of the formula] [i [
EMI1.2
 treated with 2-aminocyclohexanol or cyclopentanol, suitably with a molar equivalent thereof.



   Lower alkyl groups contained in radicals represented by the symbol R are to be understood as meaning straight-chain or branched alkyl groups with 1-6 carbon atoms. Examples are methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl and their isomers. Halophenyl represented by the symbol R is preferably chlorophenyl. An acylaminophenyl group represented by the symbol R may contain aliphatic or aromatic acyl groups. Examples of such groups are acetaminophenyl or benzoylaminophenyl. A diacylimidophenyl group is, for example, the phthalimidophenyl group.



   The starting materials of the formula II can be prepared analogously to the procedure described in the example below (cf. also the Belgian patent document No. 702 280).



   The compounds of general formula 1 obtainable according to the invention are distinguished by an exceptional blood sugar-lowering activity when administered orally. The compounds have a short residence time in the organism and are largely excreted unchanged. They can therefore be used as remedies in the form of pharmaceutical preparations which they contain as a mixture with a suitable pharmaceutical, organic or inorganic inert carrier material.



   example
2.55 g of O, N-bis-tosylcarbamoyl-trans-2-aminocyclohexanol and 0.8 g of trans-2-aminocyclohexanol are mixed with 2 ml of abs. Pyridine heated to 1200 C for 4 hours. After cooling, the reaction product is mixed with 20 ml of 1N NaOH. After filtration, the solution is saturated with CO, filtered again and acidified with 2N hydrochloric acid. The l- (p-toluenesulfonyl) -3- (trans-2-hydroxy-cyclohexyl) -urea crystallizes on standing.



   The starting material can be made as follows:
To a solution of 5.75 g of trans-2-amino-cyclohexanol in 50 ml of abs. After adding 7.5 ml of triethylamine, dimethylformamide is slowly added dropwise, with ice-cooling and stirring, to 17 ml of p-toluenesulfonyl isocyanate. After standing for 2 days at room temperature, the solvent is evaporated and the residue is dissolved in 50 ml of 2N NaOH. When the solution is saturated with CO, a brown resin is deposited, from which it is decanted. After exhaustive ether extraction, the aqueous solution is acidified with 2N hydrochloric acid. The oily O, N-bis-tosylcarbamoyl-trans-2-aminocyclohexanol which separates out crystallizes on standing.

  Melting point after reprecipitation from dilute sodium hydroxide solution and recrystallization from alcohol 200-2050 C.

Claims (1)

PATENTANSPRUCH PATENT CLAIM Verfahren zur Herstellung von Sulfonylharnstoffderi vaten der Formel EMI2.1 in der R Phenyl, das durch Halogen, Niederalkyl-, Niederalkoxy-, Niederalkylthio-, Acetyl-, Amino-, Acylami- no- oder Diacylimidogruppen substituiert sein kann, und n die Zahl 3 oder 4 bedeutet, dadurch gekennzeichnet, dass man eine Verbindung der Formel II EMI2.2 mit 2-Amino-cyclohexanol bzw. -cyclopentanol behandelt. Process for the preparation of sulfonylurea derivatives of the formula EMI2.1 in which R is phenyl, which can be substituted by halogen, lower alkyl, lower alkoxy, lower alkylthio, acetyl, amino, acylamino or diacylimido groups, and n is the number 3 or 4, characterized in that a compound the formula II EMI2.2 treated with 2-amino-cyclohexanol or -cyclopentanol. UNTERANSPRÜCHE 1. Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass man eine Verbindung der Formel II, in der R p-Tolyl darstellt und n = 4 ist, mit 2-Aminocyclohexanol umsetzt. SUBCLAIMS 1. The method according to claim, characterized in that a compound of the formula II in which R is p-tolyl and n = 4, is reacted with 2-aminocyclohexanol. 2. Verfahren nach Patentanspruch und Unteranspruch 1, dadurch gekennzeichnet, dass man O,N-Bis-Tosylcarbamoyl-trans-2-aminocyclohexanol mit trans-2-Amino cydohexanol umsetzt. 2. The method according to claim and dependent claim 1, characterized in that O, N-bis-tosylcarbamoyl-trans-2-aminocyclohexanol is reacted with trans-2-amino cydohexanol. 3. Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass man 1 Moläquivalent 2-Aminocyclohexanol bzw. -cyclopentanol einsetzt. 3. The method according to claim, characterized in that 1 mol equivalent of 2-aminocyclohexanol or -cyclopentanol is used.
CH787169A 1966-08-08 1966-08-08 Sulphonamides and process for the manufacture thereof CH510647A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CH787169A CH510647A (en) 1966-08-08 1966-08-08 Sulphonamides and process for the manufacture thereof

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CH1136566A CH500176A (en) 1966-08-08 1966-08-08 Sulphonamides and process for the manufacture thereof
CH787169A CH510647A (en) 1966-08-08 1966-08-08 Sulphonamides and process for the manufacture thereof
CH787569A CH509992A (en) 1966-08-08 1966-08-08 Process for the preparation of sulfonamides
CH787469A CH509991A (en) 1966-08-08 1966-08-08 Sulphonamides and process for the manufacture thereof

Publications (1)

Publication Number Publication Date
CH510647A true CH510647A (en) 1971-07-31

Family

ID=27429105

Family Applications (1)

Application Number Title Priority Date Filing Date
CH787169A CH510647A (en) 1966-08-08 1966-08-08 Sulphonamides and process for the manufacture thereof

Country Status (1)

Country Link
CH (1) CH510647A (en)

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