CH196552A - Process for the preparation of d-lysergic acid-l-norepheride. - Google Patents

Process for the preparation of d-lysergic acid-l-norepheride.

Info

Publication number
CH196552A
CH196552A CH196552DA CH196552A CH 196552 A CH196552 A CH 196552A CH 196552D A CH196552D A CH 196552DA CH 196552 A CH196552 A CH 196552A
Authority
CH
Switzerland
Prior art keywords
sep
lysergic acid
preparation
norepheride
acid
Prior art date
Application number
Other languages
German (de)
Inventor
Sandoz Chemische Fabri Vormals
Original Assignee
Chem Fab Vormals Sandoz
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 Chem Fab Vormals Sandoz filed Critical Chem Fab Vormals Sandoz
Publication of CH196552A publication Critical patent/CH196552A/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D457/00Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
    • C07D457/04Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid 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 in position 8
    • C07D457/06Lysergic acid amides

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Description

  

  Verfahren zur Darstellung von     d-Lysergsäure-l-norepherid.            Gegenstand    des vorliegenden Patentes ist  ein Verfahren zur     Darstellung    von     -d-Lyserg-          säure-l-no@rephedrid,        welches        dadurch    gekenn  zeichnet ist,     dass    man     rac.        Lysergsäure-azid     mit     l-Norephedrin        umsetzt    und     die    dabei       entstehenden        isomeren    Verbindungen trennt.  



       Die    rechtsdrehende Komponente     des.    End  produktes, welche     ein        .spez.    Drehvermögen  [al<B>l"</B> =     +    296   (c =     0,2e3    in     Aceton)    be  sitzt und meist nur in amorphem Zustand  erhalten wird, ist     @d'-Lysergsiäure-l-norephe-          ,drid.    Die     Zusammensetzung        mitspricht    der  Bruttoformel     C"ss"0_#N3.     



  Die neue Verbindung gibt die blaue       Kellersche    Farbreaktion und soll für thera  peutische Zwecke Verwendung finden.  



       Beispiel:     1 g frisch     hergestelltes        rac.        Lysergsäure-          azid    wird in     eine        Lösung    von 1 g     l-Nore-          phedrin    in 210     cmg    Alkohol bei 0   eingetra  gen. Beim     Verreiben    tritt rasch Lösung ein.

    Das     Lösungsmittel    wird im Vakuum abge  dampft und zur Entfernung von überschüssi-         gem        Norephedrin    der klebrige Rückstand       mehrere    Male mit je 20 cm'     Wasser        extra-          hiert.    Dann wird die     trockene,    amorphe Sub  stanz in 5     em@        absol.    Alkohol gelöst und     mit.     40     em3    Äther verdünnt.

       l-Lysergsäure-l-nore-          phedrid    scheidet sich sogleich in     glitzernden     Kristallen in Form der     Äther-A@dditionsver-          bindung    ab. Ausbeute 0,4 g.  



  Die Mutterlauge wird abgedampft, der  Rückstand in 10 cm' Alkohol gelöst und  tropfenweise, bis     keine    weitere Fällung mehr  eintritt,     alkoholische        Phosphorsäure    zuge  geben. Der     Niedersohlag        besteht    aus dem  Phosphat von     @d-Lysergsäure-l-norephiedrid,     während     Spuren    von     l-Lys,ergsiäurerl-nore-          phe,driclphosphat    in Lösung bleiben.

   Das  Phosphat wird     abgenutscht,    in 30 cm' Was  ser     gelöste    und .durch Zusatz von     Natrium-          bikarbon:at    .das Alkaloid in Freiheit gesetzt.  Es scheidet     .sich    .als in Wasser     praktisch    un  lösliche, weisse, körnige Flocken ab. Aus  beute 0,5 g.  



       d-Lysergsäure-l-norephedrid    kann durch       Umlösen    aus     Benzol    weiter     gereinigt    werden.    
EMI0002.0001     
  
    Es <SEP> schmilzt. <SEP> unscharf <SEP> zwischen <SEP> 110 <SEP> bis <SEP> <B>130'</B>
<tb>  (korr.). <SEP> Zusammensetzung <SEP> CZJH=; <SEP> 0.N;.. <SEP> Polari  sation: <SEP> 0,0233 <SEP> g <SEP> der <SEP> Verbindung <SEP> zu <SEP> 10,0 <SEP> ein'
<tb>  Aoeton <SEP> gelöst, <SEP> drehten <SEP> im <SEP> 1 <SEP> dm-Rohr <SEP> bei <SEP> 20'
<tb>  um <SEP> 0,69 <SEP>   <SEP> nach <SEP> rechts. <SEP> [a] <SEP> i; <SEP> = <SEP> + <SEP> 296 <SEP>  .
<tb>  



  Die <SEP> neuen <SEP> Verbindungen <SEP> beben <SEP> die <SEP> blaue
<tb>  Kellersche <SEP> Farbreaktion, <SEP> welche <SEP> für <SEP> '_Vlutter  kornalka.loide <SEP> charakteristisch <SEP> ist.



  Process for the preparation of d-lysergic acid-l-norepheride. The present patent is a process for the preparation of -d-lysergic acid-l-no @ rephedrid, which is characterized in that one rac. Lysergic acid acid reacts with l-norephedrine and separates the isomeric compounds that are formed.



       The clockwise component of the end product, which is a .spec. Rotational power [al <B> l "</B> = + 296 (c = 0.2e3 in acetone) and is usually only obtained in an amorphous state is @ d'-lysergic acid-l-norephe-, drid Composition corresponds to the gross formula C "ss" 0_ # N3.



  The new compound gives the blue cellar color reaction and is intended to be used for therapeutic purposes.



       Example: 1 g of freshly made rac. Lysergic acid azide is added to a solution of 1 g of l-norephedrine in 210 cmg of alcohol at 0. When rubbed in, it dissolves quickly.

    The solvent is evaporated off in vacuo and the sticky residue is extracted several times with 20 cm of water each time to remove excess norephedrine. Then the dry, amorphous substance is in 5 em @ absol. Alcohol dissolved and with. 40 em3 ether diluted.

       L-lysergic acid-l-norephedrid is immediately deposited in glittering crystals in the form of the ether-addition compound. Yield 0.4g.



  The mother liquor is evaporated, the residue is dissolved in 10 cm 'of alcohol and alcoholic phosphoric acid is added dropwise until no further precipitation occurs. The lower soil consists of the phosphate of @ d-lysergic acid-l-norephiedrid, while traces of l-lys, ergsic acid-norephe, driclphosphate remain in solution.

   The phosphate is sucked off, dissolved in 30 cm of water, and the alkaloid is set free by adding sodium bicarbonate. It separates out as white, granular flakes that are practically insoluble in water. From booty 0.5 g.



       d-Lysergic acid-l-norephedride can be further purified by dissolving it from benzene.
EMI0002.0001
  
    It <SEP> melts. <SEP> unset <SEP> between <SEP> 110 <SEP> to <SEP> <B> 130 '</B>
<tb> (corr.). <SEP> Composition <SEP> CZJH =; <SEP> 0.N; .. <SEP> polarization: <SEP> 0.0233 <SEP> g <SEP> of the <SEP> connection <SEP> to <SEP> 10.0 <SEP> on '
<tb> Aoeton <SEP> released, <SEP> turned <SEP> in <SEP> 1 <SEP> dm pipe <SEP> at <SEP> 20 '
<tb> by <SEP> 0.69 <SEP> <SEP> after <SEP> right. <SEP> [a] <SEP> i; <SEP> = <SEP> + <SEP> 296 <SEP>.
<tb>



  The <SEP> new <SEP> connections <SEP> quake <SEP> the <SEP> blue ones
<tb> Kellersche <SEP> color reaction, <SEP> which <SEP> for <SEP> '_Vlutter kornalka.loide <SEP> is characteristic <SEP>.

 

Claims (1)

PATENTANSPRUCH: Verfahren zur Darstellung von d-Lyserg- säure-l-norephedrid, dadurch gekennzeichnet, EMI0002.0004 dass <SEP> man <SEP> rae. <SEP> Lysergsäure-azid <SEP> mit <SEP> l-1 <SEP> ore phedrin <SEP> umsetzt <SEP> und <SEP> die <SEP> dabei <SEP> entstehenden <tb> isomeren <SEP> Verbindungen <SEP> trennt. <tb> d-Lyse <SEP> rl,rsäure-l-norephodri.d <SEP> schmilzt <SEP> un scharf <SEP> zwischen <SEP> 110 <SEP> bis <SEP> <B>13,0</B> <SEP> <SEP> und <SEP> entspricht <tb> der <SEP> Bruttoformel <SEP> C"H"0zN9. <SEP> [a];;' <SEP> =-f- <SEP> <B>296'.</B> <tb> Die <SEP> neue <SEP> Verbindung <SEP> gibt, <SEP> die <SEP> blaue <tb> Kellersche <SEP> Farbreaktion <SEP> und <SEP> soll <SEP> in <SEP> der <tb> Therapie <SEP> Verwendung <SEP> finden. PATENT CLAIM: Process for the preparation of d-lysergic acid-l-norephedride, characterized in EMI0002.0004 that <SEP> man <SEP> rae. <SEP> Lysergic acid-azide <SEP> with <SEP> l-1 <SEP> ore phedrine <SEP> converts <SEP> and <SEP> the <SEP> resulting <SEP> <tb> isomeric <SEP> compounds <SEP> separates. <tb> d-lysis <SEP> rl, räure-l-norephodri.d <SEP> melts <SEP> not sharp <SEP> between <SEP> 110 <SEP> to <SEP> <B> 13.0 </ B> <SEP> <SEP> and <SEP> corresponds <tb> the <SEP> gross formula <SEP> C "H" 0zN9. <SEP> [a] ;; ' <SEP> = -f- <SEP> <B> 296 '. </B> <tb> The <SEP> new <SEP> connection <SEP> gives, <SEP> the <SEP> blue one <tb> Kellersche <SEP> Color reaction <SEP> and <SEP> should <SEP> in <SEP> the <tb> Therapy <SEP> Find use <SEP>.
CH196552D 1936-06-20 1936-06-20 Process for the preparation of d-lysergic acid-l-norepheride. CH196552A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH191342T 1936-06-20
CH196552T 1936-06-20

Publications (1)

Publication Number Publication Date
CH196552A true CH196552A (en) 1938-03-15

Family

ID=4437558

Family Applications (7)

Application Number Title Priority Date Filing Date
CH191342D CH191342A (en) 1936-06-20 1936-06-20 Method for the preparation of rac. Lysergic acid ethanolamide.
CH196552D CH196552A (en) 1936-06-20 1936-06-20 Process for the preparation of d-lysergic acid-l-norepheride.
CH196550D CH196550A (en) 1936-06-20 1936-06-20 Process for the preparation of d-lysergic acid-d-isopropanolamide.
CH196551D CH196551A (en) 1936-06-20 1936-06-20 Method for the preparation of rac. Lysergic acid tyramide.
CH196549D CH196549A (en) 1936-06-20 1936-06-20 Method for the preparation of rac. Lysergic acid isopropanolamide.
CH223016D CH223016A (en) 1936-06-20 1939-06-06 Process for the preparation of d-lysergic acid-d-1-oxy-butyl-amide- (2).
CH223015D CH223015A (en) 1936-06-20 1939-06-06 Process for the preparation of d-lysergic acid-d-1-oxy-butyl-amide- (2).

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CH191342D CH191342A (en) 1936-06-20 1936-06-20 Method for the preparation of rac. Lysergic acid ethanolamide.

Family Applications After (5)

Application Number Title Priority Date Filing Date
CH196550D CH196550A (en) 1936-06-20 1936-06-20 Process for the preparation of d-lysergic acid-d-isopropanolamide.
CH196551D CH196551A (en) 1936-06-20 1936-06-20 Method for the preparation of rac. Lysergic acid tyramide.
CH196549D CH196549A (en) 1936-06-20 1936-06-20 Method for the preparation of rac. Lysergic acid isopropanolamide.
CH223016D CH223016A (en) 1936-06-20 1939-06-06 Process for the preparation of d-lysergic acid-d-1-oxy-butyl-amide- (2).
CH223015D CH223015A (en) 1936-06-20 1939-06-06 Process for the preparation of d-lysergic acid-d-1-oxy-butyl-amide- (2).

Country Status (2)

Country Link
CH (7) CH191342A (en)
FR (1) FR825057A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1034641B (en) * 1955-03-07 1958-07-24 Lilly Co Eli Process for the production of lysergic acid amides

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1096364B (en) * 1956-08-09 1961-01-05 Miroslav Semonsky Dr Ing Process for the preparation of pharmacodynamically active substituted amides of d-lysergic acid and their salts
US4902691A (en) * 1988-12-19 1990-02-20 Eli Lilly And Company Heteroalkylamides of (8-β)-1-alkyl-6-(substituted)ergolines useful for blocking 5HT2 receptors

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1034641B (en) * 1955-03-07 1958-07-24 Lilly Co Eli Process for the production of lysergic acid amides

Also Published As

Publication number Publication date
CH223016A (en) 1942-08-15
FR825057A (en) 1938-02-23
CH191342A (en) 1937-06-15
CH223015A (en) 1942-08-15
CH196549A (en) 1938-03-15
CH196551A (en) 1938-03-15
CH196550A (en) 1938-03-15

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