PL120037B1 - Process for preparing novel 6-ketodecahydroquinolines - Google Patents

Process for preparing novel 6-ketodecahydroquinolines Download PDF

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Publication number
PL120037B1
PL120037B1 PL1979225532A PL22553279A PL120037B1 PL 120037 B1 PL120037 B1 PL 120037B1 PL 1979225532 A PL1979225532 A PL 1979225532A PL 22553279 A PL22553279 A PL 22553279A PL 120037 B1 PL120037 B1 PL 120037B1
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Poland
Prior art keywords
mixture
group
formula
ketodecahydroquinolines
carbon atoms
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PL1979225532A
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English (en)
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/20Oxygen atoms
    • C07D215/22Oxygen atoms attached in position 2 or 4
    • C07D215/227Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/20Oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/48Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Quinoline Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Description

Opis patentowy opublikowano: 25.10.1983 120037 C- i ; l-LNIA Urzedu Patentowego Nitkuj IziczTiupoliiij Ludni) Int. CU C07D 215/20 Twórca wynalazku: Uprawniony z patentu: Eli Lilly and Company, Indianapolis (Stany Zjednoczone Ameryki) Sposób wytwarzania nowych 6-ketodehahydrochinolin Pnzedttniofcem wynalazku jest sposób wytwarza¬ nia nowych 6-ketodekahydrochinoiin o ogólnymi Wzorze 1, w którym R oznacza, girape alkilowa o 1—3 atomach wegla1, grape alkilowa lub grujpe benzylowa a R1 oznacza grupe o wzorze COOZ', gidlzie Z' oznacza grupe alkilowa o 1—&' aitomiach wegla luib grupe alkilowa o 1—(2 atoniach wegla pod/stawiona grupa fenyiowa.Sposób wedlug wynalazku polega na tym, ze zwiazek o ogólnym wzoirze 2, w (którym R i Z' maja wyzej podane znacizenie, poddaje sie reak¬ cji z chlorowodorkiem pitydyny i tjrójiffletókieim chromu. Zwiazki o Wzorze 2. sa nowe.Okreislemie „grapa alkilowa o 1—12 atomach we¬ gla" oznacza grupe metylowa i etylowa a oikreisle- nie „grapa alkilowa o 1—3 atomach wegla" obej¬ muje równiez grupe ptopylowa i izcpiropylowa.Zwiazki o wzorze 1 wytwarza sie postepujac jak przedstawiono na schemacie. Spoisób postepo¬ wania opisano na przykladzie tyfllko pojedynczego steroizomeru (odnosnie steireochemii mostka we¬ glowego) — izomeru 4a^, 8act. Na schemacie Z<— —CO jest acylowa grupa ochronna, gcMe Z o- znacza grupe alkilowa o 1—3 atomach wejgfla, gru¬ pe alkenyiowa o 2-^3 atomach wegla,, grupe alfci- nylowa o 2—J3 atomach wegla, grupe cykloalkilo- wa o 5—6 atomach wegla, grupe fenyiowa lub podisitawicma grupe fenyiowa, przy czym podlsitaw- nlikiem moze byc grupa metylowa, metotasylowa, 10 15 20 25 30 atom chloru i tym poidobnie w dowolnym polo¬ zeniu pierscienia fenylowego. Grape Z—CO moze stanowic, przykladowo, grupa acetylowa, propio- nylowa*, butyrylowa, proctiolilowa, akryilililowa, benzoilowa, p-tolksilowia, o^chloirobenzoilowa, m- -nietokisymlbenzodiowia i tym podobne.Zgodnie zie schematem, 4^acyloikByHcyMoheksa- non o wzorze 3 poddaje sie reakcji z asitrem a- -chlorowcometyloakrylanowym, przykladowo estrem etylowym i amina o wzorze RNH2, gdzie R ozna¬ cza g*rape alkilowa o 1^3 atomach wegla, girupe allilowa lub grupe benzylowa.Produktem tej reakcji jest mttesza(nina DL-1- ^dlstawionej-3-eitolksykar^ 5,6,7,8-ofctahydlrochinoliny i DL-il-podstawionej-HA 3,4,'4a,5^97-ok1ahydlrochlinoliny o wzorze 4, w kltó- rym kropkowana' linia oznacza alternatywne po¬ lozenie podwójnych wiazan. Otrzymane izomery przeksztalca- sie w sole chlorowodorkowe a ich mieszanine redlukuje sie cyjanoborowodorkiem so¬ dowym otrzymujac trans-DL-l^podisitawlona-B-eito- ksykanbonylo^6iacyloksydekahydlrochinoline o wzo¬ rze 5.. W wyniku hydrolizy tego dwueistnu otrzymuje sie kwas 6nhyidlroklsyr3-Jkarfooksylowy a nastepnie przez reetstryfikacje kwasowej grupy karboksylo¬ wej etanolem otrzymuje sie tranis-iDL-il-poidlstawiona-SHetoiksy- karbonylo-6-hydlroiklsyH^kahydliochkioline o wzorze 120 037120 037 3 4 sadlke ekstrakcyjna Soxleta wypelniona sitami molekularnymi typu 3A. Mieszanine reaikcyljna o- chlodizono, rozcienczono wodnym roztworom wo¬ doroweglLaiiu sodowego i alkaliczna mieszanine 5 ekstrahowano kilkakrotnie chloroformem. Eks¬ trakty chloroformowe polaczono i przemyto nasy¬ conym wodnymi roztworem chlorku sodu i suszo¬ no. Po oid|pedizeniu chlorotformiu otrzymano 10,3 g pozostalosci zawierajacej trans 10 toksyfearbonylo^-hydirolksydekianydrochinolme wy¬ tworzona w powyzszej hydrolizie po chromatografii na 150 g preparatu florisil z uzycieim chlorofor¬ mu zawierajacego zwiekszajace sie (£—10!%) ilosci metanolu jako eluenta. 15 Przygotowano rozitwor z 8,8 g transHDL-\l-(pto- pylo-B-e;to(ksyikarbonydo-6-hydlroiksyicyekahyidlrochi- noliny i 4O0 ml dwuchloirometylaniu i podano don 4,1 g octanu sodowego. Nastepnie dodano 10,8 g odczynnika chlorowodorek pirydyny, trójtlenek 20 chromu i otrzymana mlieszanine mieszano w ciagu okolo 22 godzin, po czym przesaczono i przesacz zatezono pod piróznia. Oitrzymany koncentrat roz¬ puszczono w chloroformie a roztwór chloroformo- wy poddano chromatografii na 150 g preparatu florisil z. uzyciem chloroformu zawierajacego zwiejkszajace sie .(1—12%) iloisici metanolu jako e- luenta. Metoda chromatografii ciemkowarstwowej stwierdzono, ze frakcje zawieraja trans-DL-il-pro- pylo-S-etoksyikairtoonylo-G-lketoideikahydrochinoline.Charakterystyka produktu /Izwiiazek trans o, wzo¬ rze 1, w którym R=n^CaH7 a R1=COOC2H5/ Widmo IR/CHay 1715 -cm-1 keton C=0 17i25 cm-1 ester G=0 Widdno NMR '/GOdJ /\W JYEHz/ . 53 cykle/s, triplet, N^CH2^CH2—CH3 77 cykli/ls, triplet, —O—CH2—CH3 250 cykli/s, kwartet, —O^CH2—-CH3 2. Utleniajac grupe hydroksylowa odczynnikiem • Saretta (chlorowodorek pirydyny i trójltlenek chromoi) otrzymuje sie odpowiedni nowy 6-keto zwliazelk o Wzorze 1.Zwiazki o wzorze 1 stanowia produkty posred¬ nie do wytwarzania nowych oktanydropirazolo[3,4- ig]chinolin, .które isa przydatne jaJko srodki lecz¬ nicze o dzialaniu agonistycznyrn wzgledem dopa- miny.Przyikilatd Mieszanine 10 ml propyloamfiny i 400 ml toluenu ochlodzono w mieszaninie wody z liodieni. Dodano do niej po kropli roztwór 16,5 g a-^bromometyloi/aikrylanu etylu..Otrzymana imlieszanine mieszano i chlodzono w ciagu okolo 25 mliniut. Nafstejpnie do.dlano po- kropli roztwór 11 g 4-lhenzoilloksycyklo-ihe'ksanonu w 75 ml toluenu. Te nowa mlieszanine ogtrzewano w temperaturze wrzenia pod chloidnica zwrotna w atmosferze azotu w ciagiu 213 godzin. Chlodnice zwrotna wyposazono w nasadke ekstrakcyjna Soxleta wypelniona sitami molekularnymi typu 5A w celu usuniecia wody. ¦Naistejpinlie mieszanine reakcyjna oichlodzono i przesaczono. W pozosta¬ losci {po odpedzaniu rozpuszczalników znajdowaly sie l-propylo-3-etoiklsyika^bonylo-6-lbenzoilolksy^l,2, 3,4,5,6,7,8K)k)tahydTochmolina ora-z .l-pa:opylo-3^eto- klsyikairibonylo-6-ibenzoiloiksy-il,2(^3,4,4a,i5,6,,7-olktahy- drochinolina.Pozostalosc te rozpuszczono w mieszaninie eter— chloroform i otrzymany rozfe^ór... nasycono gazo¬ wym chlorowodorem przy jednoczesnym utrzymy¬ waniu temperatury reakcji w granicach 0—5°C.Rozpuszczalnik zdekanltowano znaid krysztalów chlorowodorków tak otrzymanych. Ohlorowodbirlkji rozpuszczono w 100 ml metanolu, dodano 300 ml THF i koncowy rozitfwóirocliiojdlzono w mieszani¬ nie wody z lodem. Podczas miLeseania i ochladza¬ nia dodano nastepnie porcjami 15.sg wodoir'ku sodowego, po.czyim miesaanane reaikcyj^ na mieszano ptzez dalsze ly2l5 £odlzftny i rozcien^ czono nastepnie woidlnym roztworem weglanu so¬ dowego. , •.. .Wodina alkaliczna mieszanine eksibrajaowano da^ lej kilkakrotnie octanem etylu, ekstrakty poiaczo-.. no i przemyto nasyconym . wodnym < roztworem chlorku sodu i suszono. Po odpedzeniu rozpusz- czalniika otrzymano trans-DLnl^ropylo-G^01^ lrarbonylor^-lbenizoilofesy^ Zwiazek ten trozpmszic^ono w m&eszan^nje 400.,ml metanolu i 100 ml 2N wodoejgo rozporu wodo¬ rotlenku sodowego, mieszano -w temtperat^i^zie .po¬ kojowej w atmosferze azotu w ,. c iajgia -6^4 godzin i po tym czasie lotne substancje usunieto .przez oidjparowanie pod próznia., .Otrzymana, pozostalosc rozproszono w 800 ml etanole i li5 ml 1 2N wodL nego roztworu kwasu, sokiego. ; : Mieszanine estryfikacyjna ogrzewano w tempe¬ raturze wrzenjia pod chlodnica. zawrotna i odde¬ stylowano- okolo 300 ml rozpuszczalnika. Dodano nastepnie dalsze 300 ml etanofllu i mieszanine re- aikcyjna ogrzewano w temperaturze wrzenia w ciagu 26 godlzin w aparaturze wyposazonej w na- PL PL PL PL PL PL PL PL

Claims (1)

1.
PL1979225532A 1979-01-22 1979-06-29 Process for preparing novel 6-ketodecahydroquinolines PL120037B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US506179A 1979-01-22 1979-01-22
US06/031,641 US4198415A (en) 1979-01-22 1979-04-19 Prolactin inhibiting octahydro pyrazolo[3,4-g]quinolines

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PL120037B1 true PL120037B1 (en) 1982-02-27

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ID=26673868

Family Applications (4)

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PL1979216719A PL122153B1 (en) 1979-01-22 1979-06-29 Process for preparing novel octahydropyrazolo-/3,4-g/ quinolinesnov
PL1979225532A PL120037B1 (en) 1979-01-22 1979-06-29 Process for preparing novel 6-ketodecahydroquinolines
PL1979225533A PL119785B1 (en) 1979-01-22 1979-06-29 Method of manufacture of novel 6-hydroxydecahydroquinolines
PL1979225531A PL119715B1 (en) 1979-01-22 1979-06-29 Process for preparing novel 6-keto-7-dimethylaminomethylen-decahydroquinolinesekagidrokhinolinov

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PL1979216719A PL122153B1 (en) 1979-01-22 1979-06-29 Process for preparing novel octahydropyrazolo-/3,4-g/ quinolinesnov

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PL1979225533A PL119785B1 (en) 1979-01-22 1979-06-29 Method of manufacture of novel 6-hydroxydecahydroquinolines
PL1979225531A PL119715B1 (en) 1979-01-22 1979-06-29 Process for preparing novel 6-keto-7-dimethylaminomethylen-decahydroquinolinesekagidrokhinolinov

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US (1) US4198415A (pl)
EP (2) EP0050881B1 (pl)
AT (1) AT371819B (pl)
AU (1) AU528076B2 (pl)
CA (1) CA1136140A (pl)
CH (3) CH644377A5 (pl)
DD (5) DD148340A5 (pl)
DE (2) DE2966951D1 (pl)
DK (1) DK268879A (pl)
EG (1) EG14696A (pl)
ES (4) ES482089A1 (pl)
FI (1) FI65247C (pl)
FR (5) FR2446832A1 (pl)
GB (4) GB2040915B (pl)
GR (1) GR72516B (pl)
IE (1) IE48394B1 (pl)
IL (1) IL57668A (pl)
LU (1) LU81439A1 (pl)
MY (1) MY8500683A (pl)
NZ (2) NZ190835A (pl)
PH (3) PH14909A (pl)
PL (4) PL122153B1 (pl)
PT (1) PT69829A (pl)
RO (2) RO77563A (pl)
ZA (1) ZA793243B (pl)

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FR2578254B1 (fr) * 1985-03-01 1987-03-06 Roussel Uclaf Nouveaux derives de la pyrazolobenzoxazine, leurs sels, procede de preparation, application a titre de medicaments, compositions les renfermant, et des intermediaires
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DD144670A5 (de) 1980-10-29
EP0013787B1 (en) 1984-05-02
RO82159B (ro) 1983-06-30
IE48394B1 (en) 1985-01-09
AT371819B (de) 1983-08-10
PL119785B1 (en) 1982-01-30
IL57668A (en) 1983-06-15
FR2446822B1 (pl) 1981-10-02
AU4844579A (en) 1980-07-31
FI65247B (fi) 1983-12-30
NZ201279A (en) 1984-07-06
GB2092580A (en) 1982-08-18
ES482089A1 (es) 1980-08-01
PL122153B1 (en) 1982-06-30
AU528076B2 (en) 1983-04-14
CH644377A5 (fr) 1984-07-31
ZA793243B (en) 1981-02-25
GB2092580B (en) 1983-08-03
NZ190835A (en) 1984-07-06
FR2446820A1 (fr) 1980-08-14
IE791209L (en) 1980-07-22
DD148517A5 (de) 1981-05-27
LU81439A1 (fr) 1979-09-12
FR2446822A1 (fr) 1980-08-14
EP0050881A1 (en) 1982-05-05
PT69829A (en) 1979-07-01
PL216719A1 (pl) 1980-06-16
MY8500683A (en) 1985-12-31
FR2446821A1 (fr) 1980-08-14
PL119715B1 (en) 1982-01-30
PH14908A (en) 1982-01-29
GB2040915A (en) 1980-09-03
FR2446832A1 (fr) 1980-08-14
DE2966945D1 (de) 1984-05-30
CH644365A5 (fr) 1984-07-31
EP0013787A1 (en) 1980-08-06
IL57668A0 (en) 1979-10-31
GB2092579A (en) 1982-08-18
GB2040915B (en) 1983-05-11
FR2446832B1 (pl) 1983-08-05
CH644607A5 (fr) 1984-08-15
ATA452479A (de) 1982-12-15
GR72516B (pl) 1983-11-16
EG14696A (en) 1986-09-30
DD148340A5 (de) 1981-05-20
DE2966951D1 (en) 1984-06-07
FR2446834A1 (fr) 1980-08-14
FI65247C (fi) 1984-04-10
RO77563A (ro) 1981-11-04
ES482087A1 (es) 1980-04-01
FR2446834B1 (pl) 1982-03-05
ES482090A1 (es) 1980-04-01
GB2092581A (en) 1982-08-18
DK268879A (da) 1980-07-23
DD148518A5 (de) 1981-05-27
PH14991A (en) 1982-03-12
US4198415A (en) 1980-04-15
ES482091A1 (es) 1980-04-01
FI792046A7 (fi) 1980-07-23
DD148339A5 (de) 1981-05-20
EP0050881B1 (en) 1984-04-25
PH14909A (en) 1982-01-29
RO82159A (ro) 1983-07-07
CA1136140A (en) 1982-11-23

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