YU45099B - PROCEDURE FOR THE PRODUCTION OF N-SUBSTITUTED MORPHINANES - Google Patents

PROCEDURE FOR THE PRODUCTION OF N-SUBSTITUTED MORPHINANES

Info

Publication number
YU45099B
YU45099B YU227772A YU227772A YU45099B YU 45099 B YU45099 B YU 45099B YU 227772 A YU227772 A YU 227772A YU 227772 A YU227772 A YU 227772A YU 45099 B YU45099 B YU 45099B
Authority
YU
Yugoslavia
Prior art keywords
compound
formula
carbon atoms
give
alkyl
Prior art date
Application number
YU227772A
Other languages
Serbo-Croatian (sh)
Other versions
YU227772A (en
Inventor
I. Pachter
B. Bellean
I. Monković
Original Assignee
Bristol-Myers Company
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 Bristol-Myers Company filed Critical Bristol-Myers Company
Publication of YU227772A publication Critical patent/YU227772A/en
Publication of YU45099B publication Critical patent/YU45099B/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
    • C07D303/02—Compounds containing oxirane rings
    • C07D303/36—Compounds containing oxirane rings with hydrocarbon radicals, substituted by nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
    • C07C49/753—Unsaturated compounds containing a keto groups being part of a ring containing ether groups, groups, groups, or groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/22—Bridged ring systems
    • C07D221/28—Morphinans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
    • C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

POSTUPAK ZA PROIZVODNJU N-SUPSTITUISANIH MORFINANA, formule gde R1 predstavlja u kojima R4 predstavlja H ili CH3; R2 predstavlja H,/nizi/alkil sa 1-6 ugljenikovih atoma 2-6 atoma ugljenika, trihloracetil ili cinamoil; ili njegove farmaceutski prihvatljive kisele adicione soli, naznacen time, sto reaguje jedinjenje formule u kojoj je R2 /nizi/ alkil sa 1-6 atoma ugljenika, sa alkilujucim ili acilujucim agensom, formule W - /Z/ - X u kojoj je W radikal, odabran iz grupe, koja se sastoji od gde je R4; H ili CH3; Z je karbonil ili metilenska grupa, a X je hlor, brom ili jod, pri temperaturi od oko 15 C do oko temperature refluksa, tokom oko 5 do 20 casova, u metilenhloridu ili dietiletru, u prisustvu organskog tercijernog amina kao akceptora protona, odabranog medju trimetilaminom, trietilaminom, piridinom, dimetilanilinom, N-metilpiperidinom, - pri cemu se dobija jedinjenje formule u kojoj su R2, W i Z kao gore, sto se dobijeno jedinjenje zatim, epoksidira perbenzoevom kiselinom u metilenhloridu, pri cemu se dobija epoksid formule gde su R2, Z i W kao gore; sto navedeni epoksid reaguje sa litijumaluminijumhidridom pri povisenoj temperaturi, u benzolu, etanolu ili tetrahidrofuranu, pri cemu se dobija jedinjenje formule gde su R2 i W kao gore, a ako se zeli, sto se, potom, aciluje 14-hidroksi grupa dobijenog jedinjenja da bi se dobilo jedinjenje formule XXXXXI gde je R1 kao gore R2 je nizi alkil sa od 1-6 atoma ugljenika, a R je nizi acil sa od 2-6 atoma ugljenika, trihloracetil ili cinamoil; i sto se, po zelji, cepa etarska funkcija jedinjenja XXXXIIIc tretiranjem bromovodonicnom kiselinom, bortribromidom ili piridinhidrohloridom, pri cemu se dobija 3,14-dihidroksi jedinjenje, formule i sto se dobijeno jedinjenje, po zelji, prevodi u jedinjenje formule XXXXI, gde su R i R2 kako je gore definisano, ili u njegovu netoksicnu, farmaceutski prihvatljivu kiselu adicionu so.A process for the production of N-SUBSTITUTED MORPHINANES, of the formula wherein R 1 represents wherein R 4 represents H or CH 3; R 2 represents H, (lower) alkyl of 1-6 carbon atoms, 2-6 carbon atoms, trichloroacetyl or cinamoyl; or a pharmaceutically acceptable acid addition salt thereof, which reacts with a compound of formula wherein R 2 is / lower / alkyl of 1-6 carbon atoms, with an alkylating or acylating agent of formula W - / Z / - X wherein W is a radical, selected from the group consisting of wherein R4 is; H or CH3; Z is a carbonyl or methylene group and X is chlorine, bromine or iodine, at a temperature of about 15 C to about reflux temperature, for about 5 to 20 hours, in methylene chloride or diethyl ether, in the presence of an organic tertiary amine as a proton acceptor selected from trimethylamine, triethylamine, pyridine, dimethylaniline, N-methylpiperidine, - to give a compound of formula wherein R 2, W and Z are as above, the compound obtained is then epoxidized with perbenzoic acid in methylene chloride to give an epoxy of formula wherein R2, Z and W as above; said epoxide being reacted with lithium aluminum hydride at elevated temperature in benzene, ethanol or tetrahydrofuran to give a compound of formula wherein R 2 and W are as above and, if desired, then acylating the 14-hydroxy group of the resulting compound to there is obtained a compound of formula XXXXXI wherein R 1 is as above R 2 is lower alkyl of 1-6 carbon atoms and R is lower acyl of 2-6 carbon atoms, trichloroacetyl or cinamoyl; and optionally cleaving the ether function of compound XXXXIIIc by treatment with hydrobromic acid, boron tribromide or pyridine hydrochloride to give the 3,14-dihydroxy compound of the formula and converting the resulting compound, if desired, into a compound of formula R XXXXI, wherein and R2 as defined above, or a non-toxic, pharmaceutically acceptable acid addition salt thereof.

YU227772A 1971-09-08 1972-09-07 PROCEDURE FOR THE PRODUCTION OF N-SUBSTITUTED MORPHINANES YU45099B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US17883771A 1971-09-08 1971-09-08
US00217633A US3819635A (en) 1971-09-08 1972-01-13 14-hydroxymorphinan derivatives

Publications (2)

Publication Number Publication Date
YU227772A YU227772A (en) 1982-02-28
YU45099B true YU45099B (en) 1992-07-20

Family

ID=26874723

Family Applications (1)

Application Number Title Priority Date Filing Date
YU227772A YU45099B (en) 1971-09-08 1972-09-07 PROCEDURE FOR THE PRODUCTION OF N-SUBSTITUTED MORPHINANES

Country Status (19)

Country Link
US (1) US3819635A (en)
JP (1) JPS5310596B2 (en)
AU (1) AU470102B2 (en)
BE (1) BE788478A (en)
CA (1) CA999578A (en)
CH (1) CH590845A5 (en)
CY (1) CY980A (en)
DD (1) DD100255A5 (en)
DE (3) DE2265256C2 (en)
DK (1) DK141624B (en)
FR (1) FR2154481B1 (en)
GB (2) GB1412130A (en)
HK (1) HK2679A (en)
IE (2) IE36688B1 (en)
KE (1) KE2911A (en)
MY (1) MY7900027A (en)
NL (1) NL162072C (en)
SE (2) SE398877B (en)
YU (1) YU45099B (en)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3910920A (en) * 1973-11-07 1975-10-07 Bristol Myers Co 3,14,17-Substituted-6,7-tetramethylenemorphinans
US3980641A (en) * 1975-07-31 1976-09-14 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinans
US4017497A (en) * 1975-11-18 1977-04-12 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinan derivatives
US4052389A (en) * 1976-03-23 1977-10-04 Bristol-Myers Company Derivatives of 9,10-dihydroxy-1-(p-alkoxybenzyl)-perhydroisoquinoline oxazine-3-one
US4139534A (en) * 1977-02-17 1979-02-13 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinan derivatives
US4058531A (en) * 1976-03-23 1977-11-15 Bristol-Myers Company Process for the preparation of 14-hydroxymorphinan derivatives
JPS52136176A (en) * 1976-03-23 1977-11-14 Bristol Myers Co Method of improving 144hydroxymorphinan derivatives
GB1587831A (en) * 1977-03-23 1981-04-08 Reckitt & Colmann Prod Ltd Morphine derivatives
GB1593191A (en) * 1977-03-23 1981-07-15 Reckitt & Colmann Prod Ltd Derivatives of morphine
US4115389A (en) * 1977-05-02 1978-09-19 Bristol-Myers Company Process of N-demethylating (-)-1-(p-methoxybenzyl)-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline
US4338320A (en) * 1978-11-15 1982-07-06 The Board Of Regents Of The University Of Nebraska Esters of 6'-hydroxycinchonine, and a method of treating arrythmia with them
US4228285A (en) * 1979-02-28 1980-10-14 Bristol-Myers Company 14-Hydroxy-6-oxamorphinans and 14-hydroxy-6-oxaisomorphinans
US4272540A (en) * 1979-04-24 1981-06-09 Sisa, Incorporated 14-Methoxymorphinan-6-one compounds and therapeutic methods of treating pain and drug dependence with them
US4322427A (en) * 1981-04-16 1982-03-30 Bristol-Myers Company Analgetic compositions and methods of use
DE69414085T2 (en) * 1993-07-19 1999-03-18 Toray Industries, Inc., Tokio/Tokyo ACTIVE SUBSTANCE TO PROTECT BRAIN CELLS
AU686203B2 (en) * 1993-07-23 1998-02-05 Toray Industries, Inc. Morphinan derivative and medicinal use
CZ281174B6 (en) * 1993-08-13 1996-07-17 Galena, A.S. Process for preparing 3,14beta-dihydroxy-17-normorphinan
EP1056443B1 (en) 1998-02-25 2004-05-06 Abbott Laboratories Butorphanol sustained release formulations
US20040167164A1 (en) * 1998-05-05 2004-08-26 Jose Pozuelo Compositions and methods for treating particular chemical addictions and mental illnesses
US7501433B2 (en) * 2002-05-17 2009-03-10 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
US7923454B2 (en) 2002-05-17 2011-04-12 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
EP1506174B1 (en) 2002-05-17 2015-09-30 Taiwanj Pharmaceuticals Co., Ltd. Use of naltrexone for treating kidney and liver damage
US8017622B2 (en) 2003-05-16 2011-09-13 Jenken Biosciences, Inc. Opioid and opioid-like compounds and uses thereof
CN103073496B (en) * 2013-02-18 2015-08-26 苏州立新制药有限公司 The preparation method of Dextromethorphane Hbr
JP6464181B2 (en) 2014-10-14 2019-02-06 久光製薬株式会社 Patch

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3166559A (en) * 1965-01-19 J-lower alkoxy-x-phenyloxy-ix-hydroxy-
GB1028407A (en) * 1962-04-06 1966-05-04 Shionogi & Co Improvements in or relating to morphinan derivatives and their preparation
FR1362540A (en) * 1963-04-05 1964-06-05 Shionogi & Co Substituted n derivatives of morphinan and their production

Also Published As

Publication number Publication date
AU470102B2 (en) 1976-03-04
DK141624C (en) 1980-10-13
DE2265256C2 (en) 1985-10-24
JPS4834864A (en) 1973-05-22
US3819635A (en) 1974-06-25
YU227772A (en) 1982-02-28
HK2679A (en) 1979-01-19
GB1412130A (en) 1975-10-29
DE2265255C2 (en) 1986-06-05
GB1412129A (en) 1975-10-29
DE2265255A1 (en) 1977-01-27
MY7900027A (en) 1979-12-31
SE7506292L (en) 1975-06-02
FR2154481B1 (en) 1976-04-23
IE36688B1 (en) 1977-02-02
DK141624B (en) 1980-05-12
SE398877B (en) 1978-01-23
DD100255A5 (en) 1973-09-12
DE2265256A1 (en) 1977-01-27
FR2154481A1 (en) 1973-05-11
DE2243961A1 (en) 1973-04-05
NL162072C (en) 1980-04-15
CA999578A (en) 1976-11-09
AU4622872A (en) 1974-03-07
CH590845A5 (en) 1977-08-31
KE2911A (en) 1979-01-26
IE36687B1 (en) 1977-02-02
NL7212176A (en) 1973-03-12
IE36687L (en) 1973-03-08
NL162072B (en) 1979-11-15
BE788478A (en) 1973-03-06
CY980A (en) 1979-03-23
DE2243961C2 (en) 1988-07-21
JPS5310596B2 (en) 1978-04-14
SE403286B (en) 1978-08-07

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