NO752109L - - Google Patents
Info
- Publication number
- NO752109L NO752109L NO752109A NO752109A NO752109L NO 752109 L NO752109 L NO 752109L NO 752109 A NO752109 A NO 752109A NO 752109 A NO752109 A NO 752109A NO 752109 L NO752109 L NO 752109L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- acid
- compounds
- isopropyl
- reaction
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 11
- 150000003839 salts Chemical group 0.000 claims description 10
- 150000007513 acids Chemical class 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- ORIBUSCBDFDAIQ-GYYYEOQOSA-N methyl (6ar,9r)-4,6,6a,7,8,9,10,10a-octahydroindolo[4,3-fg]quinoline-9-carboxylate Chemical compound C1=CC(C2[C@H](NC[C@@H](C2)C(=O)OC)C2)=C3C2=CNC3=C1 ORIBUSCBDFDAIQ-GYYYEOQOSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 238000004026 adhesive bonding Methods 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000002746 orthostatic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- HYHBKLWDTGTBME-UHFFFAOYSA-N pyrazin-1-ium;chloride Chemical compound Cl.C1=CN=CC=N1 HYHBKLWDTGTBME-UHFFFAOYSA-N 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
- C07D457/04—Heterocyclic 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/02—Ergot alkaloids of the cyclic peptide type
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Description
Fremgangsmåte for fremstilling av nye heterocykliske forbindelser. Process for the production of new heterocyclic compounds.
Foreliggende forbindelse vedrorer en fremgangsmåte for fremstilling av nye heterocykliske forbindelser med formel I The present compound relates to a method for the production of new heterocyclic compounds of formula I
hvori R1betyr alkyl med 2 til 5 karbonatomer og R2betyr metyl eller etyl, idet forbindelsene med formel.I kan foreligge i fri form som base, eller i form av addisjonssalter med syrer. in which R1 means alkyl with 2 to 5 carbon atoms and R2 means methyl or ethyl, the compounds of formula I can be present in free form as a base, or in the form of addition salts with acids.
Det særegne ved fremgangsmåten i henhold til. oppfinnelsen erThe peculiarity of the procedure according to. the invention is
at et reaksjonsdyktig, funksjonelt derivat av syrer med formel II that a reactive, functional derivative of acids of formula II
hvori R. har den ovennevnte betydning, kondenseres med forbindelser med formel III in which R. has the above meaning, is condensed with compounds of formula III
hvori R2har den ovennevnte betydning, i saltform, og de erholdte forbindelsér med formel I utvinnes som en base eller som syreaddisjonssalter. wherein R2 has the above-mentioned meaning, in salt form, and the obtained compounds of formula I are recovered as a base or as acid addition salts.
R^er foretrukket forgrenet, spesielt i a-stillingen til det nitrogenatom hvortil den er bundet. R^ is preferably branched, especially in the a-position of the nitrogen atom to which it is attached.
Omsetningen utgjor en kondensasjonsreaksjon for amider og kan gjennomfores analogt med kjente metoder. The reaction constitutes a condensation reaction for amides and can be carried out analogously to known methods.
Omsetningen skjer i et under reaksjonsbetingelsene inært organisk løsningsmiddel eller en losningsmiddel-blanding i nærvær av et syrebindende middel. The reaction takes place in an organic solvent that is inert under the reaction conditions or a solvent mixture in the presence of an acid-binding agent.
F.eks. går man frem på den måte at man som reaksjonsdyktig, funksjonelt derivat av en syre med formel II .anvender det addisjonsprodukt som dannes ved omsetningen av en syre med formel II med et kloreringsmiddel og et N-di(lavere) alkylsubstituert syreamid av en alifatisk karboksylsyre med 1 til 3 karbonatomeir, som dimetylformamid eller dimetylacetamid. Likeledes kan også andre reaksjonsdyktige derivater av en syre med formel II anvendes, som kan fremstilles analogt med kjente metoder, f.eks. syreklorid-hydrokloridet, syreazidet eller blandede anhydrider av en syre med formel II med svovelsyre eller trifluoreddiksyre. E.g. one proceeds in such a way that one uses as a reactive, functional derivative of an acid of formula II the addition product formed by the reaction of an acid of formula II with a chlorinating agent and an N-di(lower) alkyl-substituted acid amide of an aliphatic carboxylic acid with 1 to 3 carbon atoms, such as dimethylformamide or dimethylacetamide. Likewise, other reactive derivatives of an acid with formula II can also be used, which can be prepared analogously with known methods, e.g. the acid chloride hydrochloride, acid azide or mixed anhydrides of an acid of formula II with sulfuric acid or trifluoroacetic acid.
Som organiske losningsmidler er f.eks. kloroform, metylenklorid, acetonitril eller dimetylformamid egnet, som syrebindende middel er tertiære organiske baser som f.eks. pyridin eller dets homologe egnet. Som klbreringsmiddel kan f.eks. anvendes tionylklorid, fosgen eller oksalylklorid. Omsetningen gjennomfores ved temperaturer mellom -30 og 0°C og under normaltrykk. As organic solvents are e.g. chloroform, methylene chloride, acetonitrile or dimethylformamide are suitable, as acid-binding agents are tertiary organic bases such as e.g. pyridine or its homologues are suitable. As a gluing agent, e.g. thionyl chloride, phosgene or oxalyl chloride are used. The reaction is carried out at temperatures between -30 and 0°C and under normal pressure.
Hensiktsmessig anvendes mol av en forbindelse med formel IIIAppropriately, moles of a compound of formula III are used
i saltform 1,2 til 2,4 mol av en syre med formel II. For forbindelsene med formel III er den foretrukne såitform hydro-kloridet. Reaksjonsforlopet er uavhengig av rekkefolgen for tilsetningen av reaksjonskomponentene. in salt form 1.2 to 2.4 mol of an acid of formula II. For the compounds of formula III, the preferred seed form is the hydrochloride. The course of the reaction is independent of the order in which the reaction components are added.
Opparbeidelsen av reaksjonsblåndingen og isoleringen av forbindelsene med formel I kan skje på i og for seg kjent måte. The preparation of the reaction mixture and the isolation of the compounds of formula I can take place in a manner known per se.
Fra de fri baser lar seg på kjent måte syreaddisjonssaltene utvinne og omvendt. From the free bases, the acid addition salts can be recovered in a known manner and vice versa.
De som utgangsprodukt anvendte forbindelser med formel IIThe compounds of formula II used as starting product
er nye og kan erholdes analogt med kjent metoder. F.eks. går man frem på den måte at forbindelser med formel IV are new and can be obtained analogously to known methods. E.g. one proceeds in such a way that compounds of formula IV
hvori R 1 har den ovennevnte betydning, under milde alkaliske betingelser, fordelaktig ved behandling med natronlut i et organiskelosningsmiddel eller en losningsmiddelblanding forsepés."og deretter gjores svakt sure. in which R 1 has the above meaning, under mild alkaline conditions, advantageously by treatment with caustic soda in an organic solvent or a solvent mixture, saponified and then made weakly acidic.
Forbindelsene med formel IV kan erholdes ved alkylering av 6-nor-9,10-dihydrolysergsyremetylester. The compounds of formula IV can be obtained by alkylation of 6-nor-9,10-dihydrolysergic acid methyl ester.
Forbindelsene med formel III er tidligere kjent.The compounds of formula III are previously known.
Forbindelsene med formel I i fri form eller i form avThe compounds of formula I in free form or in the form of
fysiologisk tålbare addisjonssalter med syrer utmerker seg ved interessante farmakodynamiske egenskaper. De kan anvendes som legemidler. Således kan de påggrunn av derés vasoaktivitet og deres arterielle,kartoniserende egenskaper anvendes for behandling av begynnende migreneangrep. På„xjrunn av deres vene-toniserende virkning kan de også finne anvendelse ved behandling av ortostatiske lidelser. physiologically tolerable addition salts with acids are distinguished by interesting pharmacodynamic properties. They can be used as medicines. Thus, due to their vasoactivity and their arterial, cartonizing properties, they can be used for the treatment of incipient migraine attacks. Due to their vein-tonic effect, they can also be used in the treatment of orthostatic disorders.
For de ovennevnte anvendelser kommer spesielt forbindelsen méd formel I hvori R^ står for isopropyl, i betraktning. For the above-mentioned applications, the compound of formula I in which R 1 stands for isopropyl is particularly taken into account.
Legemiddelpreparater kan fremstilles f.eks. i form av en losning eller en tablett ved hjelp av kjente metoder under anvendelse av vanlige hjelpe- og bærerstoffer. Pharmaceutical preparations can be prepared, e.g. in the form of a solution or a tablet by means of known methods using common excipients and carriers.
I de etterfolgende eksempler som skal illustrere oppfinnelsen,In the following examples to illustrate the invention,
er alle temperaturangivelser i uten korreksjon. Hvis fremstilling-en av utgangsforbindelsene ikke er beskrevet er disse kjente eller kan fremstilles etter i og for seg kjente eller analogt med i og for seg kjente metoder. all temperature indications are without correction. If the preparation of the starting compounds is not described, these are known or can be prepared according to per se known or analogous to per se known methods.
Betegnelsen for forbindelsen med formel I er avledet av grunnskjellettet med formel V The designation for the compound of formula I is derived from the basic skeleton of formula V
som for enkelhets skyld benevnes ergopeptin. which for simplicity is called ergopeptin.
Eksempel 1: 6-nor-6~isopropyl-9,10-dihydro-2 1 [2-metyl-5 1 cc-isopropyl-ergopeptin Example 1: 6-nor-6-isopropyl-9,10-dihydro-2 1 [2-methyl-5 1 cc-isopropyl-ergopeptin
Til en losning av 300 ml dimetylformamid og 150 ml acetonitril tildryppes ved -10 til -15°C 8,6 ml oksalylklorid opplost i 20 ml acetonitril i ldpet .av 10 min. og blandingen omrdres så videre i 10 min. Deretter tilfores ved -20°C 32 g vannfri 6-nor-6-isopropyl-9,10-dihydro-lysergsyre og det omrdres i 30 min. ved -10°C. Etter avkjdling til -20°C tilsettes 200 ml pyridin og 16,3 g (2R, 5S,10aS,10bS)-2-amino-2-metyl-5-isoprppyl-3, 6-diokso-10b-hydroksy-octahydro-8H-oxazolo£3, 2-aJpyrrolo £ 2,1-cT] pyrazin-hydroklorid og det omrdres i 2 timer ved 0°C. For opparbeidelse tilsettes 100 ml pufferldsning pH = 4 og reaksjonsblandingen ekstraheres mellom métylenklorid og 2N sodaldsning. De organiske faser vaskes 2 garcpr med vann, tdrres med natriumsulfat og inndampes til tdrrhet på rotasjonsinndamper. Den erholdte rå base loses etter tdrring i hdyvakuum i omtrent 150 ml etanol og ldsningen podes. Den i overskriften nevnte forbindelse har et smeltepunkt på 194°C (spalting) , ui To a solution of 300 ml of dimethylformamide and 150 ml of acetonitrile, at -10 to -15°C, 8.6 ml of oxalyl chloride dissolved in 20 ml of acetonitrile are added dropwise over 10 min. and the mixture is then rotated further for 10 min. 32 g of anhydrous 6-nor-6-isopropyl-9,10-dihydro-lysergic acid are then added at -20°C and the mixture is stirred for 30 minutes. at -10°C. After cooling to -20°C, 200 ml of pyridine and 16.3 g of (2R, 5S, 10aS, 10bS)-2-amino-2-methyl-5-isopropyl-3, 6-dioxo-10b-hydroxy-octahydro- 8H-oxazolo£3,2-aJpyrrolo £2,1-cT] pyrazine hydrochloride and it is stirred for 2 hours at 0°C. For work-up, 100 ml buffer solution pH = 4 is added and the reaction mixture is extracted between methylene chloride and 2N sodium hydroxide solution. The organic phases are washed 2 times with water, dried with sodium sulfate and evaporated to dryness on a rotary evaporator. The crude base obtained is dissolved after drying in high vacuum in approximately 150 ml of ethanol and the solution is inoculated. The compound mentioned in the title has a melting point of 194°C (decomposition), ui
ftxj<20>-32,3° (c = 0,995 i metanol).ftxj<20>-32.3° (c = 0.995 in methanol).
D D
Fremstilling av hydrogentartratet:Preparation of the hydrogen tartrate:
8,3 g base (C3i<H>4iN5°5)<l>oses ved omtrent 50°G i 120 ml etanol og tilsettes 2,22 g L-vinsyre opplost i omtrent 10 ml etanol. Ved avkjdling til romtemperatur utkrystalliseres saltet. Det utskilte salt skilles fra moderluten, vaskes med litt etanol og tdrres deretter ved 80°C under hdyvakuum. Smeltepunkt 200°C (spalting), [cf]<20>= -18,4° (c = 1,0 i etanol). 8.3 g of base (C3i<H>4iN5°5)<l>ose at about 50°G in 120 ml of ethanol and add 2.22 g of L-tartaric acid dissolved in about 10 ml of ethanol. When cooled to room temperature, the salt crystallizes. The separated salt is separated from the mother liquor, washed with a little ethanol and then dried at 80°C under high vacuum. Melting point 200°C (decomposition), [cf]<20>= -18.4° (c = 1.0 in ethanol).
D D
Den som utgangsmaterial anvendte 6-nor-6-isopropyl-9,10-dihydrolysergsyre kan f.eks. fremstilles ved alkylering av 6-nor-9,10-dihydrolergsyremetylester med isopropylbromid og forsepning av den således erholdte 6-nor-6-isopropyl-9,10-dihydrolysergsyremetylestere (smeltepunkt 194°C). The 6-nor-6-isopropyl-9,10-dihydrolysergic acid used as starting material can e.g. is produced by alkylation of 6-nor-9,10-dihydrolysergic acid methyl ester with isopropyl bromide and saponification of the thus obtained 6-nor-6-isopropyl-9,10-dihydrolysergic acid methyl ester (melting point 194°C).
6-nor-6-isopropyl-9,10-dihydrolysergsyre smelter ved 290°C under spalting. [_ aj ^ = -101° (c = 0,6 i metanol) . 6-nor-6-isopropyl-9,10-dihydrolysergic acid melts at 290°C during cleavage. [_ aj ^ = -101° (c = 0.6 in methanol) .
D D
Eksempel 2: 6-nor-6-isopropyl-9, l°-dihydro-2^(3-_ Example 2: 6-nor-6-isopropyl-9,1°-dihydro-2^(3-_
etyl-5-_]_ a-isopropylergopeptin_ethyl-5-_]_ a-isopropylergopeptin_
Fremstilles analogt med eksempel 1. Den i overskriften nevnte forbindelse smelter ved 176-178°C under spalting. Prepared analogously to example 1. The compound mentioned in the title melts at 176-178°C during cleavage.
[_ ctj2^ = -23° (c =0,5 i metylenklorid) .[_ ctj2^ = -23° (c =0.5 in methylene chloride) .
D D
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH853374A CH602767A5 (en) | 1974-06-21 | 1974-06-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO752109L true NO752109L (en) | 1975-12-23 |
Family
ID=4341635
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO752109A NO752109L (en) | 1974-06-21 | 1975-06-13 |
Country Status (21)
| Country | Link |
|---|---|
| JP (1) | JPS5113798A (en) |
| AT (1) | AT356292B (en) |
| AU (1) | AU503060B2 (en) |
| BE (1) | BE830441A (en) |
| CA (1) | CA1057285A (en) |
| DD (1) | DD118088A5 (en) |
| DE (1) | DE2525962A1 (en) |
| DK (1) | DK140670B (en) |
| ES (1) | ES438704A1 (en) |
| FI (1) | FI751753A7 (en) |
| FR (1) | FR2275212A1 (en) |
| GB (1) | GB1499420A (en) |
| HU (1) | HU169390B (en) |
| IE (1) | IE41564B1 (en) |
| IL (1) | IL47522A (en) |
| NL (1) | NL7507177A (en) |
| NO (1) | NO752109L (en) |
| PH (1) | PH13361A (en) |
| SE (1) | SE7506758L (en) |
| YU (1) | YU157375A (en) |
| ZA (1) | ZA753967B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH601321A5 (en) * | 1975-01-06 | 1978-07-14 | Sandoz Ag | |
| CH619468A5 (en) * | 1976-01-12 | 1980-09-30 | Sandoz Ag | |
| GB0409785D0 (en) | 2004-04-30 | 2004-06-09 | Resolution Chemicals Ltd | Preparation of cabergoline |
| GB0505965D0 (en) | 2005-03-23 | 2005-04-27 | Resolution Chemicals Ltd | Preparation of cabergoline |
| US7339060B2 (en) | 2005-03-23 | 2008-03-04 | Resolution Chemicals, Ltd. | Preparation of cabergoline |
-
1975
- 1975-06-11 DE DE19752525962 patent/DE2525962A1/en not_active Withdrawn
- 1975-06-12 DK DK266475AA patent/DK140670B/en unknown
- 1975-06-12 SE SE7506758A patent/SE7506758L/en unknown
- 1975-06-12 FI FI751753A patent/FI751753A7/fi unknown
- 1975-06-13 NO NO752109A patent/NO752109L/no unknown
- 1975-06-16 GB GB25527/75A patent/GB1499420A/en not_active Expired
- 1975-06-17 NL NL7507177A patent/NL7507177A/en not_active Application Discontinuation
- 1975-06-17 PH PH17276A patent/PH13361A/en unknown
- 1975-06-17 FR FR7518879A patent/FR2275212A1/en active Granted
- 1975-06-19 DD DD186767A patent/DD118088A5/xx unknown
- 1975-06-19 AU AU82273/75A patent/AU503060B2/en not_active Expired
- 1975-06-19 HU HUSA2806A patent/HU169390B/hu unknown
- 1975-06-19 IE IE1375/75A patent/IE41564B1/en unknown
- 1975-06-19 IL IL47522A patent/IL47522A/en unknown
- 1975-06-19 ES ES438704A patent/ES438704A1/en not_active Expired
- 1975-06-19 BE BE157509A patent/BE830441A/en unknown
- 1975-06-19 YU YU01573/75A patent/YU157375A/en unknown
- 1975-06-20 JP JP50074583A patent/JPS5113798A/ja active Pending
- 1975-06-20 AT AT473575A patent/AT356292B/en not_active IP Right Cessation
- 1975-06-20 ZA ZA3967A patent/ZA753967B/en unknown
- 1975-06-20 CA CA229,783A patent/CA1057285A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| IE41564L (en) | 1975-12-21 |
| ES438704A1 (en) | 1977-06-01 |
| DE2525962A1 (en) | 1976-01-08 |
| AU503060B2 (en) | 1979-08-23 |
| FR2275212B1 (en) | 1979-08-10 |
| YU157375A (en) | 1982-05-31 |
| CA1057285A (en) | 1979-06-26 |
| IL47522A0 (en) | 1975-08-31 |
| DK140670C (en) | 1980-03-17 |
| PH13361A (en) | 1980-03-20 |
| DD118088A5 (en) | 1976-02-12 |
| IL47522A (en) | 1977-12-30 |
| FR2275212A1 (en) | 1976-01-16 |
| DK140670B (en) | 1979-10-22 |
| AT356292B (en) | 1980-04-25 |
| DK266475A (en) | 1975-12-22 |
| ATA473575A (en) | 1979-09-15 |
| ZA753967B (en) | 1977-01-26 |
| FI751753A7 (en) | 1975-12-22 |
| BE830441A (en) | 1975-12-19 |
| JPS5113798A (en) | 1976-02-03 |
| SE7506758L (en) | 1975-12-22 |
| NL7507177A (en) | 1975-12-23 |
| AU8227375A (en) | 1976-12-23 |
| HU169390B (en) | 1976-11-28 |
| GB1499420A (en) | 1978-02-01 |
| IE41564B1 (en) | 1980-01-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6426346B1 (en) | 6-membered aromatics as factor Xa inhibitors | |
| KR950007753B1 (en) | Novel indole derivatives, preparation method thereof and pharmaceutical composition containing the same | |
| US4868331A (en) | Substituted amino-5,6,7,8-tetrahydronaphthyl-oxyacetic acids, processes for their preparation and their use as medicaments | |
| US7989494B2 (en) | Polymorphs of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide | |
| US7645759B2 (en) | Non-peptide bradykinin antagonists and pharmaceutical compositions therefrom | |
| NO153054B (en) | ANALOGY PROCEDURE FOR THE PREPARATION OF THERAPEUTIC ACTIVE CYCLIC IMINOS ACIDS | |
| NO151876B (en) | PROCEDURE AND APPARATUS FOR ANIMAL LINING | |
| TW202521533A (en) | Glp-1r agonist and therapeutic method thereof | |
| CN116262734A (en) | Novel oxopyridine compound and its preparation method and use | |
| US6080768A (en) | Derivatives of 2-amino-1,2,3,4-tetrahydronaphthalene active on the cardiovascular system | |
| NO752109L (en) | ||
| NO752493L (en) | ||
| NO744175L (en) | ||
| WO2002002519A2 (en) | THROMBIN OR FACTOR Xa INHIBITORS | |
| NO139169B (en) | ANALOGICAL PROCEDURE FOR THE PREPARATION OF THERAPEUTICALLY ACTIVE AMINOAL ALCOHOL DERIVATIVES OF TRANS-HYDROXY-CINNAMIC ACIDS | |
| NO135421B (en) | ||
| NO124430B (en) | ||
| US3499906A (en) | 5,9-diethyl-2'-hydroxy-2-substituted-6,7-benzomorphans | |
| US4791115A (en) | 2,6-dimethyl-8α-pivaloylamino-9,10-didehydro-ergoline | |
| US2912436A (en) | Brominated alkaloids | |
| US3583992A (en) | 1-methyl-d-lysergic acid-dihydroxy-alkyl-amides | |
| US2090429A (en) | Lysergic acid hydkazide and a | |
| US4035501A (en) | N-lysergyl-amino-pyridines | |
| CN103420994B (en) | As the dabigatran ester derivative and its production and use of prodrug | |
| CN103420984A (en) | Dabigatran derivative used as prodrug, and preparation method and application thereof |