GB756713A - Substituted piperidines and process of making them - Google Patents

Substituted piperidines and process of making them

Info

Publication number
GB756713A
GB756713A GB19474/54A GB1947454A GB756713A GB 756713 A GB756713 A GB 756713A GB 19474/54 A GB19474/54 A GB 19474/54A GB 1947454 A GB1947454 A GB 1947454A GB 756713 A GB756713 A GB 756713A
Authority
GB
United Kingdom
Prior art keywords
piperidine
methyl
para
diphenylmethyl
pyridine
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
GB19474/54A
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.)
BASF Schweiz AG
Original Assignee
Ciba AG
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 Ciba AG filed Critical Ciba AG
Publication of GB756713A publication Critical patent/GB756713A/en
Expired legal-status Critical Current

Links

Classifications

    • 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
    • C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • 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
    • C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/12—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
    • 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
    • C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • 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
    • C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms

Landscapes

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

Abstract

The invention comprises 2-diphenylmethylpiperidines of the formula <FORM:0756713/IV(a)/1> where R is hydrogen and R1 and R2 may be one or more halogen atoms or alkyl or alkoxy groups of up to 3 carbon atoms and R1 may also be hydrogen, or R is an aliphatic hydrocarbon residue of up to 3 carbon atoms and R1 and R2 may each be hydrogen or halogen atoms or alkyl or alkoxy groups of up to 3 carbon atoms, and acid addition salts of these compounds. The compounds are made by hydrogenating an appropriately substituted 2-diphenylmethylpyridine or a 2-diphenylmethyl-pyridinium compound which is N-substituted by a lower aliphatic hydrocarbon radical. A secondary piperidine of the formula I may be converted into a tertiary piperidine by introducing an aliphatic hydrocarbon radical R by known methods. The hydrogenation of the pyridine or pyridinium compound is suitably carried out by reaction with hydrogen in the presence of a catalyst such as platinum, nickel or copper chromite. The free base may be converted into its salts with acids such as hydrohalic, sulphuric, nitric, phosphoric, thiocyanic, acetic, propionic, oxalic, malonic, succinic, malic, methane sulphonic, ethane sulphonic, oxyethane sulphonic, benzene sulphonic or toluene sulphonic acids. Preferred products comprise compounds of the formula I in which one phenyl radical is substituted by a methyl or methoxy group. In examples: (1) 2-diphenylmethylpiperidine obtained by catalytic hydrogenation of 2-diphenylmethyl-pyridine is heated with formaldehyde and formic acid to give 2-diphenylmethyl-1-methyl piperidine which is converted into its picrate; (2) 2-diphenylmethylpyridinium methosulphate is hydrogenated in the presence of platinum oxide to give the product of (1); (3) 2-(para-chlorophenyl-phenylmethyl)-pyridine is hydrogenated to give 2-(para - chlorophenyl - phenyl - methyl) - piperidine which is converted into its hydrochloride; (4) 2 - (para:para1 - dichlorodiphenyl - methyl) pyridine is hydrogenated to give 2-(para:para1-dichlorodiphenyl - methyl) piperidine and its hydrochloride; (5) 2-diphenylmethyl-piperidine is reacted with allyl bromide to give 2-diphenylmethyl-1-allyl piperidine which is converted to its picrate; (6) 2 - (para:para1 - dimethoxy-diphenyl-methyl)-piperidine is hydrogenated to give 2 - (para:para1 - dimethoxydiphenyl - methyl) - piperidine; (7) 2 - (para:para1 - dimethyldiphenyl-methyl) pyridine is hydrogenated to 2 - (para:para1 - dimethyldiphenyl-methyl) piperidine which is converted into its hydrochloride; and (8) 2-[phenyl-(meta: para-dimethylphenyl) - methyl] - pyridine is hydrogenated to 2 - [phenyl - (meta: para - dimethylphenyl)-methyl]-piperidine. Starting materials. Substituted 2-diphenyl-methyl-pyridines are made by reacting a diphenylacetic acid derivative such as a diphenyl-acetonitrile with a 2-halogen pyridine to give a pyridyl diphenylacetic acid derivative, splitting the functional derivative of the carboxyl group and, if desired, quaternating the resulting pyridine compound. The preparation of the starting materials of Examples 1, 3, 4, 6, 7 and 8 by this method, is described.ALSO:Pharmaceutical preparations comprise 2-diphenylmethyl-piperidines of the formula: <FORM:0756713/VI/1> where R represents hydrogen, R1 and R2 are one or more halogen atoms or alkyl or alkoxy groups of up to 3 carbon atoms and R1 may also be hydrogen or R is an aliphatic hydrocarbon radical of up to 3 carbon atoms and R1 and R2 are one or more hydrogen or halogen atoms or alkyl or alkoxy groups of up to 3 carbon atoms and acid addition salts of these compounds (see Group IV(b)) admixed with an organic or inorganic carrier suitable for enteral or parenteral administration. Suitable substances which may be admixed include water, gelatine, lactose, starch, magnesium stearate, talc, vegetable oils, benzyl alcohols, gums and polyalkylene glycols. Auxiliary substances such as preservatives, stabilizing, wetting or emulsifying agents, salts to control osmolic pressure or buffer substances may be added. The preparations may be used as tablets, dragees, salves, creams, solutions suspensions or emulsions. Specified 2-diphenylmethyl-piperidines include 2-diphenylmethyl-1-methyl-piperidine, 2-(p-chlorophenyl - phenyl - methyl) - piperidine, 2 - (p - chlorophenyl - phenyl -methyl) - piperidine, 2 - (p : p1 - dichlorodi - phenyl - methyl) - piperidine, 2 - diphenyl - methyl - 1 - allyl - piperidine, 2 - (p : p1 - dimeth - oxydiphenyl methyl) - piperidine, 2 - p : p1 - dimethyldiphenyl - methyl) - piperidine and 2 - (phenyl - (m : p - dimethylphenyl) - methyl) - piperidine. In examples (1) tablets are made comprising 2 - (p : p1 - dichlorodiphenylmethyl)-piperidine, talcum, lactose, gelatine, wheat starch, arrowroot and magnesium stearate and (2) a liquid preparation is made comprising 2 - (p : p1 - dichlorodiphenylmethyl) - piperidine, sodium chloride, secondary sodium phosphate and primary sodium phosphate in water.
GB19474/54A 1953-07-06 1954-07-02 Substituted piperidines and process of making them Expired GB756713A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH756713X 1953-07-06

Publications (1)

Publication Number Publication Date
GB756713A true GB756713A (en) 1956-09-05

Family

ID=4534337

Family Applications (1)

Application Number Title Priority Date Filing Date
GB19474/54A Expired GB756713A (en) 1953-07-06 1954-07-02 Substituted piperidines and process of making them

Country Status (1)

Country Link
GB (1) GB756713A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3048594A (en) * 1957-03-22 1962-08-07 Ciba Geigy Corp 1-ethyl-2-diphenylmethyl-piperidines
EP0738714A2 (en) * 1992-02-28 1996-10-23 MERCK &amp; CO. INC. Process for preparing new fibrinogen receptor antagonists

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3048594A (en) * 1957-03-22 1962-08-07 Ciba Geigy Corp 1-ethyl-2-diphenylmethyl-piperidines
EP0738714A2 (en) * 1992-02-28 1996-10-23 MERCK &amp; CO. INC. Process for preparing new fibrinogen receptor antagonists
EP0738714A3 (en) * 1992-02-28 1996-11-20 MERCK &amp; CO. INC. Process for preparing new fibrinogen receptor antagonists

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