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GB1261481A - Benzomorphans - Google Patents

Benzomorphans

Info

Publication number
GB1261481A
GB1261481A GB250170A GB250170A GB1261481A GB 1261481 A GB1261481 A GB 1261481A GB 250170 A GB250170 A GB 250170A GB 250170 A GB250170 A GB 250170A GB 1261481 A GB1261481 A GB 1261481A
Authority
GB
United Kingdom
Prior art keywords
aryl
hydrogen
lithium reagent
alkyl
methyl
Prior art date
Legal status (The legal status 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 status listed.)
Expired
Application number
GB250170A
Inventor
Franklin Moore Robinson
Paul Stanley Anderson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
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 Merck and Co Inc filed Critical Merck and Co Inc
Publication of GB1261481A publication Critical patent/GB1261481A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
    • C07D213/20—Quaternary compounds thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/02—Preparation by ring-closure or hydrogenation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • C07D221/26—Benzomorphans

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

1,261,481. Benzomorphans. MERCK & CO. Inc. 19 Jan., 1970 [23 Jan., 1969], No. 2501/70. Heading C2C. Novel benzomorphans of the general Formula I (wherein R 2 is hydrogen, cyano, RCO or RCH 2 where R is hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, alkylcycloalkyl, alkenylcycloalkyl, methylene cycloalkyl, alkylcycloalkenyl or spiroalkyl; R 3 is alkyl, aryl or substituted aryl that is capable of forming an aryl lithium reagent; R 5 is hydrogen, alkyl, aryl or substituted aryl, provided the substituent will not react with an aryl lithium reagent; and R 9 is alkyl, aryl or substituted aryl, provided that the substituent will not react with an aryl lithium reagent) may be formed by reacting a 1,2,3,6-tetrahydropyridine (f) wherein Y is methyl or p-methoxybenzyl with a p-methoxybenzyl or methyl halide respectively rearranging the resulting quaternary salt with a lithium reagent to produce compound IVb. and cyclizing IVb with hydrobromic acid to yield I in which R 2 is methyl. This compound may be acylated at the 2<SP>1</SP> position, the acylated compound heated with cyanogen bromide to replace the 2-Me with 2-CN and hydrolysing the acyl and cyano groups to produce I in which R 2 is hydrogen. This compound may be reacted with RCOX where X is a halogen and R is as previously defined except that it is not hydrogen, and reducing the 2-acyl-2<SP>1</SP> acyloxy derivative formed to produce I wherein R 2 is -CH 2 R. The 2-acyl-2<SP>1</SP> acyloxy and the 2<SP>1</SP>-acyloxy-2- cyano derivatives may be partially hydrolysed to produce I wherein R 2 is RCO and CN respectively. The 1,2,3,6-tetrahydropyridine (f) may be produced from a correspondingly 2,5-disubstituted pyridine by forming a quaternary with a methyl or p-methoxybenzyl halide, reducing the quaternary with sodium borohydride to yield: which on hydroboration followed by peroxide oxidation gives the 4-piperidinol which may be further oxidized to 4-piperidone by pyridine/ sulphur trioxide and this product reacted with a Grignard as lithium reagent of R 5 to yield (f). Pharmaceutical compositions of the compounds I or salts thereof with the usual excipients show analgesic activity when administered orally or parenterally.
GB250170A 1969-01-23 1970-01-19 Benzomorphans Expired GB1261481A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US79357269A 1969-01-23 1969-01-23

Publications (1)

Publication Number Publication Date
GB1261481A true GB1261481A (en) 1972-01-26

Family

ID=25160231

Family Applications (1)

Application Number Title Priority Date Filing Date
GB250170A Expired GB1261481A (en) 1969-01-23 1970-01-19 Benzomorphans

Country Status (6)

Country Link
BR (1) BR6914879D0 (en)
CH (1) CH534164A (en)
DE (1) DE2002864A1 (en)
FR (1) FR2034487B1 (en)
GB (1) GB1261481A (en)
NL (1) NL7000102A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4234591A (en) * 1976-06-21 1980-11-18 Acf Chemiefarma N.V. Analgesic and morphine-antagonistic 9-phenyl-6,7-benzomorphans

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2828039A1 (en) * 1978-06-26 1980-01-10 Boehringer Sohn Ingelheim 2- (2-ALKOXYETHYL) -2'-HYDROXY-6,7-BENZOMORPHANES THEIR ACID ADDITION SALTS, THESE MEDICINAL PRODUCTS, AND METHOD FOR THE PRODUCTION THEREOF
US4208523A (en) * 1978-11-30 1980-06-17 Sterling Drug Inc. 11-Lower-alkyl-, 11-phenyl-lower-alkyl- and 11-cyclo-lower-alkyl-lower-alkyl-hexahydro-2,6-methano-3-benzazocines

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4234591A (en) * 1976-06-21 1980-11-18 Acf Chemiefarma N.V. Analgesic and morphine-antagonistic 9-phenyl-6,7-benzomorphans
US4288444A (en) * 1976-06-21 1981-09-08 Acf Chemiefarma N.V. Analgesic and morphine-antagonistic 6,7-benzomorphans

Also Published As

Publication number Publication date
DE2002864A1 (en) 1970-07-30
BR6914879D0 (en) 1973-02-08
CH534164A (en) 1973-02-28
FR2034487A1 (en) 1970-12-11
FR2034487B1 (en) 1973-04-06
NL7000102A (en) 1970-07-27

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