GB772516A - Piperidines and process of making same - Google Patents

Piperidines and process of making same

Info

Publication number
GB772516A
GB772516A GB37100/54A GB3710054A GB772516A GB 772516 A GB772516 A GB 772516A GB 37100/54 A GB37100/54 A GB 37100/54A GB 3710054 A GB3710054 A GB 3710054A GB 772516 A GB772516 A GB 772516A
Authority
GB
United Kingdom
Prior art keywords
diphenyl
acid
pyridine
give
hydrogen
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
GB37100/54A
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 GB772516A publication Critical patent/GB772516A/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
    • C07D211/10—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
    • C07D211/02—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
    • C07D211/18—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

Landscapes

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

Abstract

The invention comprises piperidines of general formula <FORM:0772516/IV(b)/1> in which R represents hydrogen or an alkyl radical containing not more than 4 carbon atoms, R1 is an alkyl or hydroxy-alkyl radical containing not more than 6 carbon atoms and in which the phenyl radicals are unsubstituted or contain alkyl or alkoxy groups containing not more than 4 carbon atoms or halogen atoms, and acid addition salts thereof. Of special importance are the compounds in which R is hydrogen and the phenyl groups are unsubstituted, e.g. 2-(11,11-diphenyl-ethyl)-piperidine and their acid addition salts. These new piperidines are obtained by hydrogenating a pyridine of formula <FORM:0772516/IV(b)/2> or a quaternary derivative thereof. The resulting secondary piperidines can be substituted at the nitrogen atom by known methods. The piperidines so obtained may then be converted into their acid addition salts. The hydrogenation may be carried out with hydrogen using a noble metal, such as platinum, or nickel or copper chromite as catalyst. Alternatively nascent hydrogen may be used with an alkali metal, such as sodium, in an alcohol such as butanol, as catalyst. For the N-substitution the usual methods may be used, e.g. reaction with formaldehyde and formic acid or hydrogen to introduce a methyl group. Therapeutically, useful acid addition salts may be obtained by reacting the free piperidine bases with acids such as hydrohalic acids, sulphuric acid, nitric acid, phosphoric acid, thiocyanic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, malic acid, methane sulphonic acid, ethane sulphonic acid, hydroxyethane sulphonic acid and benzene or toluene sulphonic acids. In the examples (a) 2-(11,11-diphenyl-ethyl)-pyridine is reduced by hydrogen in the presence of platinum oxide to give 2-(11,11-diphenyl-ethyl)-piperidine which is treated with alcoholic hydrochloric acid to give the hydrochloride; other salts, e.g. the hydrobromide, sulphate, nitrate, phosphate and acetate may be obtained similarly; (b) 2-(11,11-diphenyl-propyl)-pyridine is treated with hydrogen in the presence of nickel to give 2-(11,11 - diphenyl - propyl) - piperidine which is treated with hydrochloric acid to give the hydrochloride; (c) 2-(11,11-diphenyl-propyl)-piperidine is heated with formic acid and formaldehyde to give 1 - methyl - 2 - (11,11-diphenyl-21-hydroxy-ethyl)-pyridine is treated with hydrogen in the presence of platinum oxide to give 2-(11,11-diphenyl-21-hydroxyethyl) piperidine which is converted to the hydrochloride by treatment with hydrochloric acid; (c) 2-(11,11-diphenyl-31-hydroxypropyl)-pyridine in butanol solution is treated with sodium to give 2-(11,11-diphenyl-31-hydroxypropyl)-piperidine; and (f) 2-(11,11-diphenyl-41-hydroxybutyl)-pyridine is treated with hydrogen in the presence of platinum oxide to give 2-(11,11-diphenyl-41-hydroxybutyl)-piperidine. The pyridine derivative used as starting material in (a) is obtained by treating 2-diphenyl-methyl-pyridine with sodamide and methyl iodide; the 2-(11,11-diphenyl-propyl)-pyridine used as starting material in (b) is obtained in an analogous manner by using ethyl bromide or ethyl iodide as alkylating agent instead of methyl iodide. The starting material used in (d) above, i.e. 2-(11,11-diphenyl-21-hydroxy-ethyl)-pyridine, is obtained by treating diphenyl-pyridy-(2)-acetic acid ethyl ester with lithium-aluminium hydride; the diphenyl pyridy-(2) acetic acid ester is obtained by treating 2-diphenylmethyl-pyridine with lithium phenyl and adding chloroformic acid ethyl ester to the resulting mixture. The 2-(11,11-diphenyl-31-hydroxypropyl)-pyridine used in (e) above is obtained by an analogous method. The 2-(11,11-diphenyl-41-hydroxybutyl)-pyridine used in (f) is obtained by reacting the lithium compound from 2-diphenyl-methyl-pyridine in ether with a solution of acrylic acid ethyl ester to give 2-(11,11-diphenyl-31-carbethoxypropyl)-pyridine which is treated with lithium-aluminium hydride to give the desired compound.ALSO:New piperidine derivatives of general formula <FORM:0772516/VI/1> in which R is hydrogen or an alkyl radical containing not more than 4 carbon atoms and R1 is an alkyl or hydroxy alkyl radical containing not more than 6 carbon atoms, and in which the phenyl radicals may be substituted by alkyl or alkoxy radicals containing not more than 4 carbon atoms; and their acid addition salts may be used in pharmaceutical preparations which contain them in admixture with the adjuvant as a carrier which facilitates administration e.g. water, gelatine, lactose, starch, magnesium stearate, talc, vegetable oils, benzyl alcohols, gums, polyalkylene glycols, petroleum jelly or cholesterol. The mixtures may also contain preservatives or stabilizing, wetting or emulsifying agents.
GB37100/54A 1953-12-22 1954-12-22 Piperidines and process of making same Expired GB772516A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CH772516X 1953-12-22

Publications (1)

Publication Number Publication Date
GB772516A true GB772516A (en) 1957-04-17

Family

ID=4535529

Family Applications (1)

Application Number Title Priority Date Filing Date
GB37100/54A Expired GB772516A (en) 1953-12-22 1954-12-22 Piperidines and process of making same

Country Status (1)

Country Link
GB (1) GB772516A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3088869A (en) * 1961-08-29 1963-05-07 Smith Kline French Lab Antiemetic compositions and methods of treating nausea and vomiting
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
US3088869A (en) * 1961-08-29 1963-05-07 Smith Kline French Lab Antiemetic compositions and methods of treating nausea and vomiting
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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