CH237326A - Process for the preparation of a salt of a sulfonamide. - Google Patents

Process for the preparation of a salt of a sulfonamide.

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Publication number
CH237326A
CH237326A CH237326DA CH237326A CH 237326 A CH237326 A CH 237326A CH 237326D A CH237326D A CH 237326DA CH 237326 A CH237326 A CH 237326A
Authority
CH
Switzerland
Prior art keywords
sep
soluble
salt
calcium
water
Prior art date
Application number
Other languages
German (de)
Inventor
Ag Cilag Chemisch Laboratorium
Original Assignee
Cilag Chemisches Ind Lab Ag
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 Cilag Chemisches Ind Lab Ag filed Critical Cilag Chemisches Ind Lab Ag
Publication of CH237326A publication Critical patent/CH237326A/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/69—Benzenesulfonamido-pyrimidines

Description

  

  Verfahren zur Darstellung eines Salzes eines Sulfonamides.    Das in neuerer Zeit bekannt gewordene  2 -     (p-Acetylamino-benzol-sulf        onylamino)    -4,     6-          dimethyl-pyrimidin    hat sich als geeignet er  wiesen zur Bekämpfung infektiöser, insbeson  dere durch Kokken hervorgerufener, Krank  heiten.  



  Es wurde nun gefunden, dass das durch  Ersatz des Wasserstoffatoms seiner     Sulfon-          amidgruppe    durch Kalzium erhältliche     Kal-          ziumsalz    des     2-(p-Acetylamino-benzol-sul-          fonylamino)-4,6-dimethyl-pyrimidins    gegen  über der entsprechenden Wasserstoffverbin  dung die oben     erwähnten    therapeutischen  Eigenschaften in verstärktem Masse aufweist  und ausserdem eine bessere Verträglichkeit  besitzt, indem es insbesondere weniger Ma  genbeschwerden, Erbrechen und Kopfweh  erzeugt als das freie Sulfonamid.

   Dem in  unserem schweizerischen Patent Nr. 221515  beschriebenen     Di=[2-(p-Acetylamino-benzol-          sulfonylamino)-pyridin]-calcium    gegenüber  besitzt es den Vorteil grösserer Löslichkeit in  Wasser. Da zudem seine wässerige Lösung  beinahe neutral reagiert, eignet es sich gut    zu Injektionen, was bei dem     Di-[2-(p-Acetyl-          amino-benzol-sulfonylamino)        -pyridinl    - cal  cium nicht der Fall ist. Die neue Kalzium  verbindung soll zur Bekämpfung infektiöser  Erkrankungen, speziell der durch     Strepto-,          Gono-    und     Pneumokokken    verursachten, ver  wendet werden.  



  Das Verfahren des vorliegenden Patentes  zur Darstellung des neuen     Sulfonamidsalzes     ist dadurch gekennzeichnet, dass man     2-(p-          A        cetylamino    - Benzol -     sulfonylamino)    - 4,6 -     di-          methyl-pyrimidin    und eine zum Austausch  des Wasserstoffes der     Sulfonamidgruppe    ge  gen Kalzium befähigte Verbindung, z. B.

         galziumhydroxyd,    lösliches     Kalziumsalz,     wie     galziumchlorid,    aufeinander     einwirken     lässt, so dass sich das     Di-[2-(p-Acetylamino-          benzol    -     sulfonylamin    o) - 4,6     -dimethyl-pyrimi-          din]-calcium    bildet.

           T.        Ausführungsbeispiel:     6,4 g 2 - (p -     Acetylamino-benzol-sulfonyl-          amino)-4,6-dimethyl-pyrimidin    werden in  einer Lösung von 5 g     Kalziumhydroxyd    in    
EMI0002.0001     
  
    _r00 <SEP> em;# <SEP> Wasser <SEP> kurz <SEP> aufgekocht. <SEP> Aus <SEP> der
<tb>  beiss <SEP> filtrierten <SEP> Lösung <SEP> kristallisieren <SEP> beim
<tb>  Abkühlen <SEP> 6,5 <SEP> b <SEP> Kalziumsalz <SEP> des <SEP> ?-(p- <SEP> Acetyl  amino- <SEP> Benzol <SEP> -sulfonylamino) <SEP> - <SEP> 4.6 <SEP> - <SEP> dimetliyl  pyrimidins <SEP> aus. <SEP> Die <SEP> Ausbeute <SEP> kann <SEP> durch
<tb>  Einengen <SEP> der <SEP> Mutterlauge <SEP> erhöht <SEP> werden.
<tb>  



  <I>2. <SEP> Ausführungsbeispiel:</I>
<tb>  Eine <SEP> Lösung <SEP> von <SEP> 0,8 <SEP> g <SEP> Natriumliydrozy(1
<tb>  und <SEP> 6.4g <SEP> ?-(p-Acetylamino-benzol-sulfonyl  rimirio)-1,6-dimethyl-pyrimidin <SEP> in <SEP> <B>1,10</B> <SEP> ein
<tb>  Nasser <SEP> wird <SEP> in <SEP> der <SEP> Siedehitze <SEP> mit <SEP> einer <SEP> Lö  sung <SEP> von <SEP> 4,:

  5 <SEP> g <SEP> Kalziumchlorid <SEP> in <SEP> 1.0 <SEP> ein"
<tb>  Wasser <SEP> versetzt. <SEP> Beim <SEP> Erkalten <SEP> li#ristallisi@#  ren <SEP> 6,6 <SEP> g <SEP> @i-@?-(p-Acetylamino-Lenzol-sul  fonylamino)-4,6-dimetliyl-pyrimidin] <SEP> -caleiuni
<tb>  aus. <SEP> Eine <SEP> weitere <SEP> Menge <SEP> des <SEP> Salzes <SEP> hann
<tb>  durch <SEP> Einengen <SEP> der <SEP> Mutterlauge <SEP> gewonnen
<tb>  werden. <SEP> Zwecks <SEP> Reinigung <SEP> wird <SEP> es <SEP> vorteil  haft <SEP> aus <SEP> heissem <SEP> Wasser <SEP> umkristallisiert.
<tb>  



  Das <SEP> Endprodukt <SEP> bildet <SEP> farblose, <SEP> derbe
<tb>  Prismen <SEP> (aus <SEP> Nasser). <SEP> Beim <SEP> Erhitzen <SEP> zer  setzt <SEP> es <SEP> sich, <SEP> ohne <SEP> zn <SEP> schmelzen. <SEP> Eist <SEP> gut
<tb>  löslich <SEP> in <SEP> heissem <SEP> Wasser <SEP> und <SEP> in <SEP> Formamid,
<tb>  wenig <SEP> löslich <SEP> in <SEP> Alkohol, <SEP> sehr <SEP> wenig <SEP> löslich
<tb>  ii! <SEP> Äther <SEP> und <SEP> in <SEP> Kohlenwasserstoffen.



  Process for the preparation of a salt of a sulfonamide. The recently known 2- (p-acetylamino-benzene-sulfonylamino) -4, 6- dimethyl-pyrimidine has proven to be suitable for combating infectious diseases, in particular those caused by cocci.



  It has now been found that the calcium salt of 2- (p-acetylamino-benzene-sulphonylamino) -4,6-dimethyl-pyrimidine, which can be obtained by replacing the hydrogen atom of its sulfonamide group with calcium, compared to the corresponding hydrogen compound Has above-mentioned therapeutic properties to a greater extent and also has better tolerability, in that it produces less stomach problems, vomiting and headaches than the free sulfonamide.

   Compared to the di = [2- (p-acetylamino-benzenesulfonylamino) -pyridine] -calcium described in our Swiss patent No. 221515, it has the advantage of greater solubility in water. Since its aqueous solution reacts almost neutrally, it is well suited for injections, which is not the case with di- [2- (p-acetylamino-benzene-sulfonylamino) -pyridinium-calcium. The new calcium compound will be used to combat infectious diseases, especially those caused by streptococci, gonococci and pneumococci.



  The process of the present patent for the preparation of the new sulfonamide salt is characterized in that 2- (p-acetylamino-benzene-sulfonylamino) -4,6-dimethyl-pyrimidine and one of the hydrogen of the sulfonamide group are able to exchange for calcium Connection, e.g. B.

         Galziumhydroxyd, soluble calcium salt, such as Galziumchlorid, let act on each other, so that the di- [2- (p-acetylaminobenzene - sulfonylamine o) - 4,6-dimethyl-pyrimidine] -calcium is formed.

           T. Exemplary embodiment: 6.4 g of 2 - (p - acetylamino-benzene-sulfonyl-amino) -4,6-dimethyl-pyrimidine are in a solution of 5 g of calcium hydroxide in
EMI0002.0001
  
    _r00 <SEP> em; # <SEP> water <SEP> briefly <SEP> boiled up. <SEP> From <SEP> the
<tb> at <SEP> filtered <SEP> solution <SEP> crystallize <SEP> at
<tb> cooling down <SEP> 6.5 <SEP> b <SEP> calcium salt <SEP> of the <SEP>? - (p- <SEP> acetyl amino- <SEP> benzene <SEP> -sulfonylamino) <SEP> - <SEP> 4.6 <SEP> - <SEP> dimetliyl pyrimidins <SEP>. <SEP> The <SEP> yield <SEP> can <SEP> through
<tb> Concentrate <SEP> the <SEP> mother liquor <SEP> increase <SEP>.
<tb>



  <I> 2. <SEP> Embodiment: </I>
<tb> A <SEP> solution <SEP> of <SEP> 0.8 <SEP> g <SEP> sodium liydrozy (1
<tb> and <SEP> 6.4g <SEP>? - (p-Acetylamino-benzene-sulfonyl rimirio) -1,6-dimethyl-pyrimidine <SEP> in <SEP> <B> 1.10 </B> < SEP> a
<tb> Wet <SEP> becomes <SEP> in <SEP> the <SEP> boiling point <SEP> with <SEP> a <SEP> solution <SEP> of <SEP> 4 ,:

  5 <SEP> g <SEP> calcium chloride <SEP> in <SEP> 1.0 <SEP> on "
<tb> water <SEP> added. <SEP> When <SEP> cools down <SEP> li # ristallisi @ # ren <SEP> 6.6 <SEP> g <SEP> @i - @? - (p-Acetylamino-Lenzol-sulphonylamino) -4.6 -dimetliyl-pyrimidine] <SEP> -caleiuni
<tb> off. <SEP> One <SEP> more <SEP> amount <SEP> of the <SEP> salt <SEP> hann
<tb> obtained by <SEP> concentration <SEP> of the <SEP> mother liquor <SEP>
<tb> be. <SEP> For <SEP> cleaning <SEP>, <SEP> it <SEP> is advantageously <SEP> recrystallized from <SEP> hot <SEP> water <SEP>.
<tb>



  The <SEP> end product <SEP> forms <SEP> colorless, <SEP> coarse
<tb> Prisms <SEP> (from <SEP> Nasser). <SEP> When <SEP> is heated, <SEP> decomposes <SEP>, <SEP> without <SEP> to <SEP> melt. <SEP> Ice <SEP> is good
<tb> soluble <SEP> in <SEP> hot <SEP> water <SEP> and <SEP> in <SEP> formamide,
<tb> little <SEP> soluble <SEP> in <SEP> alcohol, <SEP> very <SEP> little <SEP> soluble
<tb> ii! <SEP> ether <SEP> and <SEP> in <SEP> hydrocarbons.

Claims (1)

EMI0002.0002 PATENTANSPRUCH: <tb> Verfahren <SEP> zur <SEP> Darstellung <SEP> eine., <SEP> Salzes <tb> eines <SEP> Sitlfoiianiicles, <SEP> dadurch <SEP> gekennzeichnet, <tb> dass <SEP> man <SEP> ?-(p-_1cc#tylan <SEP> @ino-bcnzol-sulfonyl ,iniino)-4,fi-dirnetliyl-p.#-rimidin <SEP> und <SEP> eine <SEP> zum <tb> Aust; EMI0002.0002 PATENT CLAIM: <tb> Method <SEP> for <SEP> representation <SEP> a., <SEP> salt <tb> of a <SEP> Sitlfoiianiicles, <SEP> characterized by <SEP>, <tb> that <SEP> man <SEP>? - (p-_1cc # tylan <SEP> @ ino-bcnzol-sulfonyl, iniino) -4, fi-dirnetliyl-p. # - rimidin <SEP> and <SEP> a <SEP> to <tb> Aust; iuscli <SEP> des <SEP> Wasserstoffes <SEP> der <SEP> Sulfon aniidgruppe <SEP> gegen <SEP> Kalzium <SEP> befähigte <SEP> Ver bindung <SEP> aufeinander <SEP> einwirken <SEP> lässt, <SEP> so <SEP> <B>d <SEP> ass</B> <tb> sieh <SEP> das <SEP> Di-[2-(p-Acel,ylamino-benzol-sijl fonylaniino)-4,6-dimetliyl-pyrimidin] <SEP> -ca.lcium <tb> bildet. <tb> Das <SEP> Verfahrensprodukt <SEP> bildet <SEP> farblose, <tb> derhe <SEP> Prismen <SEP> (rius <SEP> Wasser). <SEP> Beim <SEP> Erhitzen <tb> zersetzt <SEP> es <SEP> sieh. <SEP> ohne <SEP> zu <SEP> schmelzen. <SEP> Es <SEP> ist <SEP> gut <tb> löslich <SEP> in <SEP> heissem <SEP> -Wasser <SEP> und <SEP> in <SEP> Formamid. <tb> wenig <SEP> löslich <SEP> in <SEP> Alkohol, <SEP> sehr <SEP> wenig <SEP> löslich <tb> iii <SEP> Äther <SEP> und <SEP> in <SEP> Kohlenwasserstoffen. iuscli <SEP> of the <SEP> hydrogen <SEP> of the <SEP> sulfonic aniide group <SEP> against <SEP> calcium <SEP> capable <SEP> compound <SEP> can act on each other <SEP> <SEP>, <SEP > so <SEP> <B> d <SEP> ass </B> <tb> see <SEP> the <SEP> di- [2- (p-acel, ylamino-benzene-sijl fonylaniino) -4,6-dimethyl-pyrimidine] <SEP> -ca.lcium <tb> forms. <tb> The <SEP> process product <SEP> forms <SEP> colorless, <tb> derhe <SEP> prisms <SEP> (rius <SEP> water). <SEP> During <SEP> heating <tb> decomposes <SEP> see it <SEP>. <SEP> without <SEP> to <SEP> melt. <SEP> It <SEP> is <SEP> good <tb> soluble <SEP> in <SEP> hot <SEP> water <SEP> and <SEP> in <SEP> formamide. <tb> little <SEP> soluble <SEP> in <SEP> alcohol, <SEP> very <SEP> little <SEP> soluble <tb> iii <SEP> ether <SEP> and <SEP> in <SEP> hydrocarbons. <SEP> Die <tb> neue <SEP> Verbindung <SEP> soll <SEP> zur <SEP> Bekämpfung <SEP> infek tiöser <SEP> Erkranknngen, <SEP> speziell <SEP> der <SEP> durch <tb> Strepto-. <SEP> Gono- <SEP> und <SEP> Pneumokokken <SEP> verur sachten, <SEP> Ver@veridting <SEP> finden. <SEP> The <tb> new <SEP> connection <SEP> should <SEP> to <SEP> fight <SEP> infectious <SEP> diseases, <SEP> especially <SEP> the <SEP> <tb> Strepto-. <SEP> Gono- <SEP> and <SEP> pneumococci <SEP> caused, find <SEP> Ver @ veridting <SEP>.
CH237326D 1943-03-13 1943-03-13 Process for the preparation of a salt of a sulfonamide. CH237326A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH237326T 1943-03-13
CH213815T 1943-03-13

Publications (1)

Publication Number Publication Date
CH237326A true CH237326A (en) 1945-04-15

Family

ID=25725501

Family Applications (1)

Application Number Title Priority Date Filing Date
CH237326D CH237326A (en) 1943-03-13 1943-03-13 Process for the preparation of a salt of a sulfonamide.

Country Status (1)

Country Link
CH (1) CH237326A (en)

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