BE889905A - HETEROPROSTAGLANDIN DERIVATIVES AND THEIR PREPARATION METHODS - Google Patents

HETEROPROSTAGLANDIN DERIVATIVES AND THEIR PREPARATION METHODS Download PDF

Info

Publication number
BE889905A
BE889905A BE0/205621A BE205621A BE889905A BE 889905 A BE889905 A BE 889905A BE 0/205621 A BE0/205621 A BE 0/205621A BE 205621 A BE205621 A BE 205621A BE 889905 A BE889905 A BE 889905A
Authority
BE
Belgium
Prior art keywords
emi
derivatives
heteroprostaglandin
preparation methods
represents hydrogen
Prior art date
Application number
BE0/205621A
Other languages
French (fr)
Original Assignee
Sanofi Sa
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 Sanofi Sa filed Critical Sanofi Sa
Publication of BE889905A publication Critical patent/BE889905A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/10—Spiro-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
    • C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
    • C07C405/0033—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing sulfur
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
    • C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
    • C07C45/60—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in six-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
    • C07C45/66—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups by dehydration
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
    • C07D339/02—Five-membered rings
    • C07D339/06—Five-membered rings having the hetero atoms in positions 1 and 3, e.g. cyclic dithiocarbonates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing alicyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)

Description

       

   <EMI ID=1.1> 

DE PREPARATION 

  
 <EMI ID=2.1> 

  
La présente invention se rapporte d'une manière générale à des dérivée do prostaglandines et plus particulièrement à de nouveaux composée de etruc-

  
 <EMI ID=3.1> 

  

 <EMI ID=4.1> 


  
 <EMI ID=5.1> 

  
dé la manière suivante :

  

 <EMI ID=6.1> 


  
 <EMI ID=7.1>  

  

 <EMI ID=8.1> 


  
 <EMI ID=9.1> 

  
 <EMI ID=10.1> 

  
que l'hydroxyde de sodium.

  
 <EMI ID=11.1> 

  

 <EMI ID=12.1> 


  
 <EMI ID=13.1> 
 <EMI ID=14.1> 
 
 <EMI ID=15.1> 
 <EMI ID=16.1>  

  
 <EMI ID=17.1>   <EMI ID=18.1> 
 <EMI ID=19.1> 
 <EMI ID=20.1> 
 <EMI ID=21.1> 
 <EMI ID=22.1>   <EMI ID=23.1> 

  

 <EMI ID=24.1> 


  
 <EMI ID=25.1> 

  
 <EMI ID=26.1> 

  

 <EMI ID=27.1> 


  
 <EMI ID=28.1>   <EMI ID=29.1> 

  
 <EMI ID=30.1> 

  

 <EMI ID=31.1> 


  
 <EMI ID=32.1> 

  
et à température ambiante, pour obtenir les dérivés oxoéthylènedithio-

  
 <EMI ID=33.1> 

  

 <EMI ID=34.1> 


  
dana laquelle R a la même signification que précédemment.

  
 <EMI ID=35.1> 

  
 <EMI ID=36.1> 

  
 <EMI ID=37.1> 

  

 <EMI ID=38.1> 


  
 <EMI ID=39.1> 

A 

  
B. Pr&#65533;prration du Synthon B

  
 <EMI ID=40.1> 

  
 <EMI ID=41.1> 

  
 <EMI ID=42.1> 

  

 <EMI ID=43.1> 


  
 <EMI ID=44.1> 

  
C. Préparation du Synthon C

  
 <EMI ID=45.1> 

  
de formule générale :

  

 <EMI ID=46.1> 


  
 <EMI ID=47.1> 

L 

  
 <EMI ID=48.1> 

  
 <EMI ID=49.1> 

  
formule générale :

  

 <EMI ID=50.1> 


  
 <EMI ID=51.1>  <EMI ID=52.1>  <EMI ID=53.1> 

  
 <EMI ID=54.1> 

  
 <EMI ID=55.1> 

  
 <EMI ID=56.1> 

  

 <EMI ID=57.1> 


  
 <EMI ID=58.1> 

  

 <EMI ID=59.1> 
 

  
 <EMI ID=60.1> 

  
 <EMI ID=61.1>  inerte avec l'acétate de pyrrolidine ou l'acétate de pipéridine dans un oolvant approprié, tel que le toluène et à une température allant:

  
 <EMI ID=62.1> 

  
 <EMI ID=63.1> 

  

 <EMI ID=64.1> 


  
 <EMI ID=65.1> 

  
F. Préparation du Synthon F

  
 <EMI ID=66.1> 

  
 <EMI ID=67.1> 

  
 <EMI ID=68.1> 

  

 <EMI ID=69.1> 


  
 <EMI ID=70.1> 

  
. 

  
(finirai" 

  

 <EMI ID=71.1> 


  
 <EMI ID=72.1> 

  
 <EMI ID=73.1> 

  
 <EMI ID=74.1> 

  

 <EMI ID=75.1> 


  
 <EMI ID=76.1> 

  
 <EMI ID=77.1> 
 <EMI ID=78.1> 
 <EMI ID=79.1>  
 <EMI ID=80.1> 
 <EMI ID=81.1> 

  
gtoéralo : 

  

 <EMI ID=82.1> 


  
 <EMI ID=83.1>  
 <EMI ID=84.1> 
 <EMI ID=85.1> 
 <EMI ID=86.1> 
 <EMI ID=87.1> 

  

 <EMI ID=88.1> 
 

  
 <EMI ID=89.1> 

  

 <EMI ID=90.1> 


  
 <EMI ID=91.1> 
 <EMI ID=92.1> 
  <EMI ID=93.1> 

  
ce mélange étant par la ('mite hydrogène à pression atmosphérique sur

  
 <EMI ID=94.1> 

  
ci-dessus, <EMI ID=95.1>  <EMI ID=96.1> 

  

 <EMI ID=97.1> 


  
 <EMI ID=98.1> 

  
 <EMI ID=99.1> 

  
 <EMI ID=100.1> 

  

 <EMI ID=101.1> 


  
 <EMI ID=102.1>  
 <EMI ID=103.1> 
 <EMI ID=104.1> 

  
 <EMI ID=105.1> 

  
 <EMI ID=106.1> 

  
 <EMI ID=107.1> 

  
acétal-2 (R)-heptyloxy-3 cyclopentane de formule générale :

  

 <EMI ID=108.1> 


  
 <EMI ID=109.1> 

  
 <EMI ID=110.1> 

  
Mit

  
 <EMI ID=111.1> 

  

 <EMI ID=112.1> 


  
 <EMI ID=113.1>  
 <EMI ID=114.1> 
 <EMI ID=115.1> 

  
 <EMI ID=116.1> 

  

 <EMI ID=117.1> 


  
 <EMI ID=118.1> 

  
 <EMI ID=119.1> 

  
soit

  
 <EMI ID=120.1>   <EMI ID=121.1> 

  

 <EMI ID=122.1> 


  
 <EMI ID=123.1> 

  
 <EMI ID=124.1> 

  

 <EMI ID=125.1> 


  
 <EMI ID=126.1> 

  
t&#65533;nul8 ....&18  
 <EMI ID=127.1> 
 <EMI ID=128.1> 

  

 <EMI ID=129.1> 


  
 <EMI ID=130.1> 

  
'W8w ,-".iy  
 <EMI ID=131.1> 
 <EMI ID=132.1>   <EMI ID=133.1>  

  
 <EMI ID=134.1>  

  
 <EMI ID=135.1> 

  
P.F. : 129-130[deg.]C

  
 <EMI ID=136.1> 

  
 <EMI ID=137.1> 

  
form4 au cours de la réaction et ce au moyen d'une trompe à eau de façon

  
 <EMI ID=138.1> 

  
 <EMI ID=139.1> 

  
 <EMI ID=140.1> 

  
 <EMI ID=141.1> 

  
 <EMI ID=142.1> 

  
 <EMI ID=143.1> 

  
noua pression réduite.

  
De cette manière, on obtient le composé IV après cristallisation dama l'éther de pétrole.

  
 <EMI ID=144.1> 

  

 <EMI ID=145.1> 
 

  
 <EMI ID=146.1> 

  
ajouta 9g de comparé IV pain lorsque le solide est dissous, on introduit

  
 <EMI ID=147.1> 

  
 <EMI ID=148.1> 

  
 <EMI ID=149.1> 

  
sur couche mince (solvant : chloroforme/ether éthylique 3/1). On détruit

  
 <EMI ID=150.1> 

  
 <EMI ID=151.1> 

  
Après évaporation des solvants, on récupère une huile Jaune.

  
 <EMI ID=152.1> 

  
dans l'éthanol aqueux.

  
 <EMI ID=153.1> 

  
 <EMI ID=154.1> 

  
 <EMI ID=155.1> 
 <EMI ID=156.1> 
 <EMI ID=157.1>  

  
 <EMI ID=158.1> 

  
 <EMI ID=159.1> 

  
 <EMI ID=160.1> 

  

 <EMI ID=161.1> 


  
 <EMI ID=162.1> 
 <EMI ID=163.1> 
 <EMI ID=164.1>  Coeme ce composé est particulièrement instable, il est réduit en (R)-

  
 <EMI ID=165.1> 

  
risât Ion"

  

 <EMI ID=166.1> 


  
 <EMI ID=167.1> 

  
 <EMI ID=168.1> 

  
 <EMI ID=169.1> 

  
 <EMI ID=170.1> 

  

 <EMI ID=171.1> 


  
 <EMI ID=172.1> 

R- 

  
 <EMI ID=173.1> 
 <EMI ID=174.1> 
  <EMI ID=175.1> 

  

 <EMI ID=176.1> 


  
 <EMI ID=177.1> 
 <EMI ID=178.1> 
  <EMI ID=179.1> 
 <EMI ID=180.1> 
 
 <EMI ID=181.1> 
 <EMI ID=182.1>  

S.M.

  
 <EMI ID=183.1> 

  
EXEMPLE 5

  
 <EMI ID=184.1> 

  
 <EMI ID=185.1> 

  
 <EMI ID=186.1> 

  
 <EMI ID=187.1> 

  
 <EMI ID=188.1> 

  
 <EMI ID=189.1> 

  
produit désiré cristallise dans l'éther de petrole.

  
De cette manière, on obtient le composé XII souhaité avec un rendement

  
 <EMI ID=190.1> 

  
 <EMI ID=191.1> 

  
 <EMI ID=192.1> 
 <EMI ID=193.1> 
 <EMI ID=194.1>  

  
Lorsque la solution est devenue claire, on la reprend dama du dichloro-

  
 <EMI ID=195.1> 

  
 <EMI ID=196.1> 

  
 <EMI ID=197.1> 

  
 <EMI ID=198.1> 

  
 <EMI ID=199.1>  <EMI ID=200.1> 

  
solution benzénique 2N en acétate de pyrrolidine.

  
On abandonne le milieu réactionnel durant environ 8 heures à OOC puis on

  
 <EMI ID=201.1> 

  
la phase organique et on la concentre soue pression réduite. L'aldéhyde

  
 <EMI ID=202.1> 

  
 <EMI ID=203.1> 

  
l'étape suivante.

  
Do cette manière, on obtient le compose XIV souhaité ou Synthon E. R.M.N. à 60 MHz

  

 <EMI ID=204.1> 


  
 <EMI ID=205.1>   <EMI ID=206.1> 

  
 <EMI ID=207.1> 

  
 <EMI ID=208.1> 

  
Aprèr, 30 minutes d'agitation à température ambiante, on filtre la solu-

  
 <EMI ID=209.1> 

  
 <EMI ID=210.1> 

  
réduite pour obtenir une huile foncée que l'on purifie par chromatographie

  
 <EMI ID=211.1> 

  
 <EMI ID=212.1> 

  
forae d'une huile incolore.

  
 <EMI ID=213.1> 

  

 <EMI ID=214.1> 


  
 <EMI ID=215.1> 

  
 <EMI ID=216.1> 

  
esbi&#65533;te.

  
 <EMI ID=217.1> 

  
 <EMI ID=218.1>   <EMI ID=219.1> 

  
 <EMI ID=220.1> 

  
 <EMI ID=221.1> 

  
 <EMI ID=222.1> 

  

 <EMI ID=223.1> 


  
 <EMI ID=224.1> 

  
 <EMI ID=225.1> 

  
 <EMI ID=226.1> 

  
 <EMI ID=227.1> 

  
 <EMI ID=228.1> 

  
 <EMI ID=229.1> 

  
 <EMI ID=230.1> 

  

 <EMI ID=231.1> 


  
 <EMI ID=232.1>  
 <EMI ID=233.1> 
 <EMI ID=234.1>   <EMI ID=235.1> 

  

 <EMI ID=236.1> 


  
 <EMI ID=237.1> 

  

 <EMI ID=238.1> 


  
 <EMI ID=239.1>   <EMI ID=240.1> 

  

 <EMI ID=241.1> 


  
 <EMI ID=242.1> 

  

 <EMI ID=243.1> 


  
8IIl4J

  
 <EMI ID=244.1> 

  

 <EMI ID=245.1> 


  
 <EMI ID=246.1> 

  
 <EMI ID=247.1>  

  
 <EMI ID=248.1> 

  

 <EMI ID=249.1> 


  
 <EMI ID=250.1> 
 <EMI ID=251.1> 
 
 <EMI ID=252.1> 
 <EMI ID=253.1> 

  

 <EMI ID=254.1> 


  
SJ4.

  
 <EMI ID=255.1>  <EMI ID=256.1>  

  
 <EMI ID=257.1> 

  
on reprend par le chlorure de méthylène.

  
 <EMI ID=258.1> 

  
sodiua et on concentre. On sépare alorn par chromatographie aur couche mince l'huile résultante (solvant: éther éthylique/éther de pétrole 1/1).

  
 <EMI ID=259.1>  .noua forme d'une huile incolore.

  
 <EMI ID=260.1> 

  

 <EMI ID=261.1> 


  
 <EMI ID=262.1> 

  

 <EMI ID=263.1> 


  
 <EMI ID=264.1> 
 <EMI ID=265.1> 
 
 <EMI ID=266.1> 
 <EMI ID=267.1> 

  
 <EMI ID=268.1> 

  
 <EMI ID=269.1> 

  
1 

  
 <EMI ID=270.1> 

  
compooé.

  
 <EMI ID=271.1> 

  
 <EMI ID=272.1> 

  
 <EMI ID=273.1> 

S. H.

  
 <EMI ID=274.1> 

  
 <EMI ID=275.1>  
 <EMI ID=276.1> 
 <EMI ID=277.1> 

  

 <EMI ID=278.1> 


  
 <EMI ID=279.1> 

  

 <EMI ID=280.1> 
 

  
 <EMI ID=281.1>   <EMI ID=282.1> 

  

 <EMI ID=283.1> 


  
 <EMI ID=284.1>  

  
 <EMI ID=285.1> 
 <EMI ID=286.1> 
 <EMI ID=287.1> 

  

 <EMI ID=288.1> 
 

  
 <EMI ID=289.1> 

  
cT<l&#65533;p<eKc*.

  

 <EMI ID=290.1> 


  
 <EMI ID=291.1> 

  
Eg&#65533;t :.."':)1

  

 <EMI ID=292.1> 


  
 <EMI ID=293.1> 

  

 <EMI ID=294.1> 


  
 <EMI ID=295.1>  Ce composé a été obtenu colon la méthode décrite à l'Exemple 7d) cideasua.

  

 <EMI ID=296.1> 


  
 <EMI ID=297.1> 

  
pentane.

  

 <EMI ID=298.1> 


  
 <EMI ID=299.1> 

  

 <EMI ID=300.1> 


  
 <EMI ID=301.1> 

  
 <EMI ID=302.1> 

  

 <EMI ID=303.1> 




   <EMI ID = 1.1>

OF PREPARATION

  
 <EMI ID = 2.1>

  
The present invention relates generally to derivatives of prostaglandins and more particularly to new compounds of etruc-

  
 <EMI ID = 3.1>

  

 <EMI ID = 4.1>


  
 <EMI ID = 5.1>

  
as follows :

  

 <EMI ID = 6.1>


  
 <EMI ID = 7.1>

  

 <EMI ID = 8.1>


  
 <EMI ID = 9.1>

  
 <EMI ID = 10.1>

  
than sodium hydroxide.

  
 <EMI ID = 11.1>

  

 <EMI ID = 12.1>


  
 <EMI ID = 13.1>
 <EMI ID = 14.1>
 
 <EMI ID = 15.1>
 <EMI ID = 16.1>

  
 <EMI ID = 17.1> <EMI ID = 18.1>
 <EMI ID = 19.1>
 <EMI ID = 20.1>
 <EMI ID = 21.1>
 <EMI ID = 22.1> <EMI ID = 23.1>

  

 <EMI ID = 24.1>


  
 <EMI ID = 25.1>

  
 <EMI ID = 26.1>

  

 <EMI ID = 27.1>


  
 <EMI ID = 28.1> <EMI ID = 29.1>

  
 <EMI ID = 30.1>

  

 <EMI ID = 31.1>


  
 <EMI ID = 32.1>

  
and at room temperature, to obtain the oxoethylenedithio- derivatives

  
 <EMI ID = 33.1>

  

 <EMI ID = 34.1>


  
in which R has the same meaning as before.

  
 <EMI ID = 35.1>

  
 <EMI ID = 36.1>

  
 <EMI ID = 37.1>

  

 <EMI ID = 38.1>


  
 <EMI ID = 39.1>

AT

  
B. Pr &#65533; prration of Synthon B

  
 <EMI ID = 40.1>

  
 <EMI ID = 41.1>

  
 <EMI ID = 42.1>

  

 <EMI ID = 43.1>


  
 <EMI ID = 44.1>

  
C. Preparation of Synthon C

  
 <EMI ID = 45.1>

  
of general formula:

  

 <EMI ID = 46.1>


  
 <EMI ID = 47.1>

L

  
 <EMI ID = 48.1>

  
 <EMI ID = 49.1>

  
general formula:

  

 <EMI ID = 50.1>


  
 <EMI ID = 51.1> <EMI ID = 52.1> <EMI ID = 53.1>

  
 <EMI ID = 54.1>

  
 <EMI ID = 55.1>

  
 <EMI ID = 56.1>

  

 <EMI ID = 57.1>


  
 <EMI ID = 58.1>

  

 <EMI ID = 59.1>
 

  
 <EMI ID = 60.1>

  
 <EMI ID = 61.1> inert with pyrrolidine acetate or piperidine acetate in a suitable solvent, such as toluene and at a temperature ranging:

  
 <EMI ID = 62.1>

  
 <EMI ID = 63.1>

  

 <EMI ID = 64.1>


  
 <EMI ID = 65.1>

  
F. Preparation of Synthon F

  
 <EMI ID = 66.1>

  
 <EMI ID = 67.1>

  
 <EMI ID = 68.1>

  

 <EMI ID = 69.1>


  
 <EMI ID = 70.1>

  
.

  
(will finish "

  

 <EMI ID = 71.1>


  
 <EMI ID = 72.1>

  
 <EMI ID = 73.1>

  
 <EMI ID = 74.1>

  

 <EMI ID = 75.1>


  
 <EMI ID = 76.1>

  
 <EMI ID = 77.1>
 <EMI ID = 78.1>
 <EMI ID = 79.1>
 <EMI ID = 80.1>
 <EMI ID = 81.1>

  
gtoéralo:

  

 <EMI ID = 82.1>


  
 <EMI ID = 83.1>
 <EMI ID = 84.1>
 <EMI ID = 85.1>
 <EMI ID = 86.1>
 <EMI ID = 87.1>

  

 <EMI ID = 88.1>
 

  
 <EMI ID = 89.1>

  

 <EMI ID = 90.1>


  
 <EMI ID = 91.1>
 <EMI ID = 92.1>
  <EMI ID = 93.1>

  
this mixture being by the ('hydrogen moth at atmospheric pressure on

  
 <EMI ID = 94.1>

  
above, <EMI ID = 95.1> <EMI ID = 96.1>

  

 <EMI ID = 97.1>


  
 <EMI ID = 98.1>

  
 <EMI ID = 99.1>

  
 <EMI ID = 100.1>

  

 <EMI ID = 101.1>


  
 <EMI ID = 102.1>
 <EMI ID = 103.1>
 <EMI ID = 104.1>

  
 <EMI ID = 105.1>

  
 <EMI ID = 106.1>

  
 <EMI ID = 107.1>

  
acetal-2 (R) -heptyloxy-3 cyclopentane of general formula:

  

 <EMI ID = 108.1>


  
 <EMI ID = 109.1>

  
 <EMI ID = 110.1>

  
Mit

  
 <EMI ID = 111.1>

  

 <EMI ID = 112.1>


  
 <EMI ID = 113.1>
 <EMI ID = 114.1>
 <EMI ID = 115.1>

  
 <EMI ID = 116.1>

  

 <EMI ID = 117.1>


  
 <EMI ID = 118.1>

  
 <EMI ID = 119.1>

  
is

  
 <EMI ID = 120.1> <EMI ID = 121.1>

  

 <EMI ID = 122.1>


  
 <EMI ID = 123.1>

  
 <EMI ID = 124.1>

  

 <EMI ID = 125.1>


  
 <EMI ID = 126.1>

  
t &#65533; nul8 .... & 18
 <EMI ID = 127.1>
 <EMI ID = 128.1>

  

 <EMI ID = 129.1>


  
 <EMI ID = 130.1>

  
'W8w, - ". Iy
 <EMI ID = 131.1>
 <EMI ID = 132.1> <EMI ID = 133.1>

  
 <EMI ID = 134.1>

  
 <EMI ID = 135.1>

  
M.P .: 129-130 [deg.] C

  
 <EMI ID = 136.1>

  
 <EMI ID = 137.1>

  
form4 during the reaction by means of a water pump so

  
 <EMI ID = 138.1>

  
 <EMI ID = 139.1>

  
 <EMI ID = 140.1>

  
 <EMI ID = 141.1>

  
 <EMI ID = 142.1>

  
 <EMI ID = 143.1>

  
reduced pressure.

  
In this way, compound IV is obtained after crystallization from petroleum ether.

  
 <EMI ID = 144.1>

  

 <EMI ID = 145.1>
 

  
 <EMI ID = 146.1>

  
added 9g of compared IV bread when the solid is dissolved, we introduce

  
 <EMI ID = 147.1>

  
 <EMI ID = 148.1>

  
 <EMI ID = 149.1>

  
on a thin layer (solvent: chloroform / ethyl ether 3/1). We destroy

  
 <EMI ID = 150.1>

  
 <EMI ID = 151.1>

  
After evaporation of the solvents, a yellow oil is recovered.

  
 <EMI ID = 152.1>

  
in aqueous ethanol.

  
 <EMI ID = 153.1>

  
 <EMI ID = 154.1>

  
 <EMI ID = 155.1>
 <EMI ID = 156.1>
 <EMI ID = 157.1>

  
 <EMI ID = 158.1>

  
 <EMI ID = 159.1>

  
 <EMI ID = 160.1>

  

 <EMI ID = 161.1>


  
 <EMI ID = 162.1>
 <EMI ID = 163.1>
 <EMI ID = 164.1> As this compound is particularly unstable, it is reduced to (R) -

  
 <EMI ID = 165.1>

  
risât Ion "

  

 <EMI ID = 166.1>


  
 <EMI ID = 167.1>

  
 <EMI ID = 168.1>

  
 <EMI ID = 169.1>

  
 <EMI ID = 170.1>

  

 <EMI ID = 171.1>


  
 <EMI ID = 172.1>

R-

  
 <EMI ID = 173.1>
 <EMI ID = 174.1>
  <EMI ID = 175.1>

  

 <EMI ID = 176.1>


  
 <EMI ID = 177.1>
 <EMI ID = 178.1>
  <EMI ID = 179.1>
 <EMI ID = 180.1>
 
 <EMI ID = 181.1>
 <EMI ID = 182.1>

S.M.

  
 <EMI ID = 183.1>

  
EXAMPLE 5

  
 <EMI ID = 184.1>

  
 <EMI ID = 185.1>

  
 <EMI ID = 186.1>

  
 <EMI ID = 187.1>

  
 <EMI ID = 188.1>

  
 <EMI ID = 189.1>

  
desired product crystallizes from petroleum ether.

  
In this way, the desired compound XII is obtained with a yield

  
 <EMI ID = 190.1>

  
 <EMI ID = 191.1>

  
 <EMI ID = 192.1>
 <EMI ID = 193.1>
 <EMI ID = 194.1>

  
When the solution has become clear, it is taken again dama of dichloro-

  
 <EMI ID = 195.1>

  
 <EMI ID = 196.1>

  
 <EMI ID = 197.1>

  
 <EMI ID = 198.1>

  
 <EMI ID = 199.1> <EMI ID = 200.1>

  
2N benzene solution in pyrrolidine acetate.

  
The reaction medium is left for about 8 hours at OOC and then

  
 <EMI ID = 201.1>

  
the organic phase and it is concentrated under reduced pressure. Aldehyde

  
 <EMI ID = 202.1>

  
 <EMI ID = 203.1>

  
the next step.

  
In this way, we obtain the desired compound XIV or Synthon E. R.M.N. at 60 MHz

  

 <EMI ID = 204.1>


  
 <EMI ID = 205.1> <EMI ID = 206.1>

  
 <EMI ID = 207.1>

  
 <EMI ID = 208.1>

  
After 30 minutes of stirring at room temperature, the solution is filtered.

  
 <EMI ID = 209.1>

  
 <EMI ID = 210.1>

  
reduced to obtain a dark oil which is purified by chromatography

  
 <EMI ID = 211.1>

  
 <EMI ID = 212.1>

  
forae of a colorless oil.

  
 <EMI ID = 213.1>

  

 <EMI ID = 214.1>


  
 <EMI ID = 215.1>

  
 <EMI ID = 216.1>

  
esbi &#65533; te.

  
 <EMI ID = 217.1>

  
 <EMI ID = 218.1> <EMI ID = 219.1>

  
 <EMI ID = 220.1>

  
 <EMI ID = 221.1>

  
 <EMI ID = 222.1>

  

 <EMI ID = 223.1>


  
 <EMI ID = 224.1>

  
 <EMI ID = 225.1>

  
 <EMI ID = 226.1>

  
 <EMI ID = 227.1>

  
 <EMI ID = 228.1>

  
 <EMI ID = 229.1>

  
 <EMI ID = 230.1>

  

 <EMI ID = 231.1>


  
 <EMI ID = 232.1>
 <EMI ID = 233.1>
 <EMI ID = 234.1> <EMI ID = 235.1>

  

 <EMI ID = 236.1>


  
 <EMI ID = 237.1>

  

 <EMI ID = 238.1>


  
 <EMI ID = 239.1> <EMI ID = 240.1>

  

 <EMI ID = 241.1>


  
 <EMI ID = 242.1>

  

 <EMI ID = 243.1>


  
8IIl4J

  
 <EMI ID = 244.1>

  

 <EMI ID = 245.1>


  
 <EMI ID = 246.1>

  
 <EMI ID = 247.1>

  
 <EMI ID = 248.1>

  

 <EMI ID = 249.1>


  
 <EMI ID = 250.1>
 <EMI ID = 251.1>
 
 <EMI ID = 252.1>
 <EMI ID = 253.1>

  

 <EMI ID = 254.1>


  
SJ4.

  
 <EMI ID = 255.1> <EMI ID = 256.1>

  
 <EMI ID = 257.1>

  
the residue is taken up in methylene chloride.

  
 <EMI ID = 258.1>

  
sodiua and we concentrate. The resulting oil is then separated by thin layer chromatography (solvent: ethyl ether / petroleum ether 1/1).

  
 <EMI ID = 259.1>. Forms a colorless oil.

  
 <EMI ID = 260.1>

  

 <EMI ID = 261.1>


  
 <EMI ID = 262.1>

  

 <EMI ID = 263.1>


  
 <EMI ID = 264.1>
 <EMI ID = 265.1>
 
 <EMI ID = 266.1>
 <EMI ID = 267.1>

  
 <EMI ID = 268.1>

  
 <EMI ID = 269.1>

  
1

  
 <EMI ID = 270.1>

  
compooé.

  
 <EMI ID = 271.1>

  
 <EMI ID = 272.1>

  
 <EMI ID = 273.1>

S. H.

  
 <EMI ID = 274.1>

  
 <EMI ID = 275.1>
 <EMI ID = 276.1>
 <EMI ID = 277.1>

  

 <EMI ID = 278.1>


  
 <EMI ID = 279.1>

  

 <EMI ID = 280.1>
 

  
 <EMI ID = 281.1> <EMI ID = 282.1>

  

 <EMI ID = 283.1>


  
 <EMI ID = 284.1>

  
 <EMI ID = 285.1>
 <EMI ID = 286.1>
 <EMI ID = 287.1>

  

 <EMI ID = 288.1>
 

  
 <EMI ID = 289.1>

  
cT <l &#65533; p <eKc *.

  

 <EMI ID = 290.1>


  
 <EMI ID = 291.1>

  
Eg &#65533; t: .. "':) 1

  

 <EMI ID = 292.1>


  
 <EMI ID = 293.1>

  

 <EMI ID = 294.1>


  
 <EMI ID = 295.1> This compound was obtained using the method described in Example 7d) cideasua.

  

 <EMI ID = 296.1>


  
 <EMI ID = 297.1>

  
pentane.

  

 <EMI ID = 298.1>


  
 <EMI ID = 299.1>

  

 <EMI ID = 300.1>


  
 <EMI ID = 301.1>

  
 <EMI ID = 302.1>

  

 <EMI ID = 303.1>

Claims (1)

Revendications <EMI ID=304.1> Claims <EMI ID = 304.1> <EMI ID=305.1>  <EMI ID = 305.1> <EMI ID=306.1>  <EMI ID = 306.1> <EMI ID=307.1>  <EMI ID = 307.1> auquel ils août attachée, représentent un groupement carbonyle et Z représente hydrogène ou hydroxy ainsi que les sels de métaux alcalins to which they are attached, represent a carbonyl group and Z represents hydrogen or hydroxy as well as the alkali metal salts <EMI ID=308.1>  <EMI ID = 308.1> <EMI ID=309.1>  <EMI ID = 309.1> <EMI ID=310.1>  <EMI ID = 310.1> <EMI ID=311.1>  <EMI ID = 311.1> <EMI ID=312.1>  <EMI ID = 312.1> <EMI ID=313.1>  <EMI ID = 313.1> <EMI ID=314.1> <EMI ID=315.1>  <EMI ID = 314.1>   <EMI ID = 315.1> <EMI ID=316.1>  <EMI ID = 316.1> <EMI ID=317.1>  <EMI ID = 317.1> et Z' représente hydrogène ou un radical 0-R, and Z 'represents hydrogen or an O-R radical, <EMI ID=318.1>  <EMI ID = 318.1> pour obtenir : to get : <EMI ID=319.1>  <EMI ID = 319.1> lesquelles X représente hydrogène ou hydroxy which X represents hydrogen or hydroxy liait linked <EMI ID=320.1>  <EMI ID = 320.1> <EMI ID=321.1>  <EMI ID = 321.1> dans laquelle Z représente hydrogène ou hydroxy, dérivé@ que l'on in which Z represents hydrogen or hydroxy, derivative @ which is <EMI ID=322.1> <EMI ID=323.1>  <EMI ID = 322.1> <EMI ID = 323.1> <EMI ID=324.1>  <EMI ID = 324.1> <EMI ID=325.1>  <EMI ID = 325.1> w w <EMI ID=326.1>  <EMI ID = 326.1> <EMI ID=327.1>  <EMI ID = 327.1> et A est tel que : <EMI ID=328.1> and A is such that: <EMI ID = 328.1> <EMI ID=329.1> - lorsque B représente <EMI ID=330.1> , A représente  <EMI ID = 329.1> - when B represents  <EMI ID = 330.1>  , A represents <EMI ID=331.1>  <EMI ID = 331.1> <EMI ID=332.1>  <EMI ID = 332.1> <EMI ID=333.1> <EMI ID=334.1> <EMI ID=335.1>  <EMI ID = 333.1>  <EMI ID = 334.1>   <EMI ID = 335.1> <EMI ID=336.1>  <EMI ID = 336.1> Ir "JI lL"* Ir "JI lL" * <EMI ID=337.1>  <EMI ID = 337.1> <EMI ID=338.1>  <EMI ID = 338.1> <EMI ID=339.1>  <EMI ID = 339.1> rqw6omlu rqw6omlu <EMI ID=340.1>  <EMI ID = 340.1> <EMI ID=341.1>  <EMI ID = 341.1> ..I.HW <EMI ID=342.1> <EMI ID=343.1> <EMI ID=344.1> <EMI ID=345.1> <EMI ID=346.1> <EMI ID=347.1> ..I.HW  <EMI ID = 342.1>  <EMI ID = 343.1>  <EMI ID = 344.1>  <EMI ID = 345.1> <EMI ID = 346.1> <EMI ID = 347.1> <EMI ID=348.1>  <EMI ID = 348.1> <EMI ID=349.1>  <EMI ID = 349.1> <EMI ID=350.1>  <EMI ID = 350.1> <EMI ID=351.1> <EMI ID=352.1>  <EMI ID = 351.1>  <EMI ID = 352.1> - . w...b.... -. w ... b .... <EMI ID=353.1>  <EMI ID = 353.1> <EMI ID=354.1>  <EMI ID = 354.1> <EMI ID=355.1>  <EMI ID = 355.1> <EMI ID=356.1>  <EMI ID = 356.1> <EMI ID=357.1>  <EMI ID = 357.1> <EMI ID=358.1>  <EMI ID = 358.1> <EMI ID=359.1> <EMI ID=360.1>  <EMI ID = 359.1> <EMI ID = 360.1> <EMI ID=361.1>  <EMI ID = 361.1> <EMI ID=362.1> <EMI ID=363.1>  <EMI ID = 362.1>  <EMI ID = 363.1> <EMI ID=364.1>  <EMI ID = 364.1> 'Wa 9 futà" l&#65533;e 'Wa 9 futà "l &#65533; e <EMI ID=365.1>  <EMI ID = 365.1> <EMI ID=366.1>  <EMI ID = 366.1> <EMI ID=367.1>  <EMI ID = 367.1> <EMI ID=368.1>  <EMI ID = 368.1> <EMI ID=369.1>  <EMI ID = 369.1> <EMI ID=370.1>  <EMI ID = 370.1> <EMI ID=371.1>  <EMI ID = 371.1> <EMI ID=372.1>  <EMI ID = 372.1> <EMI ID=373.1>  <EMI ID = 373.1> <EMI ID=374.1>  <EMI ID = 374.1> <EMI ID=375.1>  <EMI ID = 375.1> <EMI ID=376.1>  <EMI ID = 376.1> <EMI ID=377.1>   <EMI ID = 377.1> "en "in <EMI ID=378.1> <EMI ID=379.1>  <EMI ID = 378.1> <EMI ID = 379.1>
BE0/205621A 1980-08-12 1981-08-10 HETEROPROSTAGLANDIN DERIVATIVES AND THEIR PREPARATION METHODS BE889905A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB8026240 1980-08-12

Publications (1)

Publication Number Publication Date
BE889905A true BE889905A (en) 1982-02-10

Family

ID=10515399

Family Applications (1)

Application Number Title Priority Date Filing Date
BE0/205621A BE889905A (en) 1980-08-12 1981-08-10 HETEROPROSTAGLANDIN DERIVATIVES AND THEIR PREPARATION METHODS

Country Status (8)

Country Link
JP (1) JPS5754141A (en)
KR (2) KR840002175B1 (en)
AT (1) AT378179B (en)
BE (1) BE889905A (en)
HU (1) HU185645B (en)
MA (1) MA19238A1 (en)
SU (1) SU1145925A3 (en)
ZA (1) ZA814947B (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3346657C1 (en) * 1983-12-23 1985-01-24 Braun Ag, 6000 Frankfurt Rocker arm drive for small electrical devices
DE3346655C1 (en) * 1983-12-23 1985-01-24 Braun Ag, 6000 Frankfurt Device for converting the rotary movement of an eccentric into a reciprocating movement

Also Published As

Publication number Publication date
SU1145925A3 (en) 1985-03-15
KR830006158A (en) 1983-09-17
KR850000670B1 (en) 1985-05-09
HU185645B (en) 1985-03-28
KR850002757A (en) 1985-05-15
ZA814947B (en) 1982-07-28
MA19238A1 (en) 1982-04-01
AT378179B (en) 1985-06-25
KR840002175B1 (en) 1984-11-26
JPS5754141A (en) 1982-03-31
ATA354581A (en) 1984-11-15

Similar Documents

Publication Publication Date Title
EP0001534B1 (en) Pyrrole derivatives, method for their preparation and their therapeutical use
EP0012643A2 (en) 1-Phenyl-3-(4-piperidyl)-propan-1-one derivatives, processes for their preparation, and medicaments containing them
BE1003843A4 (en) Stereospecific PROCESS FOR PREPARATION OF THE FURO ENANTIOMERS (3,4-C) PYRIDINE COMPOUNDS AND THEREBY.
EP0102283B1 (en) Process for the preparation of quinuclidine derivatives substituted in position 3
EP0042322B1 (en) Indene derivatives, their preparation and medicines containing them
SU910118A3 (en) Process for producing n -glucofuranozid-6-yl-n -nitrosocarbamide
BE889905A (en) HETEROPROSTAGLANDIN DERIVATIVES AND THEIR PREPARATION METHODS
FR2523977A1 (en) METHOD AND KEY INTERMEDIATE COMPOUNDS FOR THE PREPARATION OF 19-NORANDROSTENEDIONE
CH650516A5 (en) 20-ISONITRIL 17 (20) UNSATURATED STEROID DERIVATIVES, THEIR PREPARATION PROCESS AND THEIR USE IN THE PREPARATION OF 17ALPHA-HYDROXY 20-CETO STEROIDS.
EP0074873A1 (en) Derivatives of 3-phenoxy-3-propanol, their preparation and their therapeutic use
CH646694A5 (en) DERIVATIVES OF 3,4,5-TRIMETHOXY CINNAMOYLE PIPERAZINE AND THEIR PREPARATION PROCESS.
CH638183A5 (en) PYRROLIDINE AND PIPERIDINE DERIVATIVES.
EP0005654B1 (en) Process for the isomerization of 3-vinyl-piperidine derivatives
FR2560873A1 (en) PIPERIDINE DERIVATIVE MEDICINES, NOVEL PIPERIDINE DERIVATIVES AND METHODS FOR PREPARING THE SAME
EP0708759B1 (en) Method for preparing substituted pyrazines
FR2468587A1 (en) NEW VITAMIN D3 DERIVATIVE, ITS THERAPEUTIC USES, ITS PREPARATION AND INTERMEDIATES OF ITS PREPARATION
US5171867A (en) Method of preparing 2,5-dimethyl-4-hydroxy-2h-furan-3-one
FR2509306A1 (en) NOVEL CYCLOPENTENE DERIVATIVES USEFUL AS SYNTHESIS INTERMEDIATES AND PROCESS FOR THEIR PREPARATION
EP0067106B1 (en) Phenol ethers active on the cardiovascular system, process for their preparation and their use in medicines
EP0097550B1 (en) Process for the preparation of cystamine derivatives having an oncostatic activity
EP0215722A1 (en) Method for the preparation of D-ribose
EP0403318A1 (en) Process for the preparation of an anti-tumor substance, 3-amino-1-(2-amino-1H-imidazolyl-4)-2-chloro-1-propanol and his salts in the threo-racemic-form, for use as a medicament
FR2555180A1 (en) DIALCOXY-4,5-DIOXOLAN-1,3-CARBOXYLIC-2 ACIDS, THEIR DERIVATIVES, PROCESS FOR PREPARING THEM AND THEIR APPLICATION
EP0082059A1 (en) Alpha-Beta-unsaturated oxime ethers, process for their preparation and their use as medicines
FR2633622A1 (en) SULFONYL INDOLIZINE DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS SYNTHESIS INTERMEDIATES

Legal Events

Date Code Title Description
RE Patent lapsed

Owner name: SANOFI

Effective date: 19870831