GB1441519A - Cinchonidine and cinchonidine derivatives - Google Patents

Cinchonidine and cinchonidine derivatives

Info

Publication number
GB1441519A
GB1441519A GB5284374A GB5284374A GB1441519A GB 1441519 A GB1441519 A GB 1441519A GB 5284374 A GB5284374 A GB 5284374A GB 5284374 A GB5284374 A GB 5284374A GB 1441519 A GB1441519 A GB 1441519A
Authority
GB
United Kingdom
Prior art keywords
trifluoromethyl
ethyl
bis
compound
piperidyl
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
GB5284374A
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.)
F Hoffmann La Roche AG
Original Assignee
F Hoffmann La Roche 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 F Hoffmann La Roche AG filed Critical F Hoffmann La Roche AG
Publication of GB1441519A publication Critical patent/GB1441519A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic 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
    • C07D215/16—Heterocyclic 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
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic 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
    • C07D215/12—Heterocyclic 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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic 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
    • C07D215/16—Heterocyclic 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
    • C07D215/18—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C07D453/04—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine

Landscapes

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

Abstract

1441519 Cinchonidine and cinchonine derivatives F HOFFMANN-LA ROCHE & CO AG 6 Dec 1974 [7 Dec 1973] 52843/74 Heading C2C Novel compounds of the Formulµ I and II wherein R 1 is halogen or CF 3 and R 2 is ethyl or vinyl, enantiomers and racemates and acid addition salts thereof may be prepared by (a) reacting a compound of the Formula III or an enantiomer or a racemate thereof with a compound of the Formula IV (b) reducing a compound of the Formula V or an enantiomer or a racemate thereof, (c) hydroxylating a compound of the Formula VI or (d) cyclising a compound of the Formula VII or an enantiomer or racemate thereof and optionally reducing a vinyl group at R 2 if present to an ethyl group, resolving a racemate, forming an acid addition salt from a free base or from another acid addition salt or forming a base from an acid-addition salt. Intermediates of Formula III are prepared by cyclizing a 1,1 - dichloro - 3[3(ethyl or vinyl)- 4-piperidinyl]propan-2-ol. Intermediates of the Formula IV are prepared by cyclizing an R 1 substituted aniline with ethyl 4,4,4-trifluoroacetoacetate to yield an R 1 -substituted - 2 - trifluoromethyl - 4 - quinolinol followed by bromination to an R 1 -substituted-2- trifluoromethyl - 4 - bromoquinoline and thereafter formation of the lithium compound in situ. 2<SP>1</SP>,8<SP>1</SP> - Bis(trifluoromethyl) - dihydrocinchonidinone racemate and 2<SP>1</SP>,8<SP>1 </SP>- bis(trifluoromethyl) - dihydrocinchoninone racemate are prepared by cyclizing isomeric erythro-1,1- dichloro - 3 - (3 - ethyl - 4 - piperidinyl) - propan - 2# - ol hydrochlorides by treatment with base, silver nitrate and then ethanol and hydrogen chloride to yield racemic ethyl 4,5-erythro-5- ethyl - quininelidine - 2# - carboxylate which on reaction with 2,8-bis(trifluoromethyl)-4-quinolyl lithium, generated in situ from the 4-bromo compound, yields the required intermediates. 21,81 - Bis(trifluoromethyl) - desorydihydrocinchonidine and 2<SP>1</SP>,8<SP>1</SP> - bis(trifluoromethyl)- desoxydihydrocinchonine are prepared by cyclizing 2-trifluoromethylaniline with 1,1,1-trifluoro- 2,4 - pentanedione to form. 2,8 - Bis(trifluoromethyl)lepidine which on reaction with a lithium compound and then methyl 3(R)-ethyl-4(5)- piperidine acetate yields 2,8-bis(trifluoromethyl)- 4 - [3 - (3(R) - ethyl - 4(S) - piperidyl) - 2 - oxopropyl] - quinoline which is reduced to an epimeric mixture of 2,8-bis(trifluoromethyl)-4- [3 - (3(R) - ethyl - 4(S) - piperidyl) - 2# - hydroxy propyl] - quinolines which is esterified to an epimeric mixture of 2,8-bis(trifluoromethyl)-4- [3 - (3(R) - ethyl - 4(S) - piperidyl) - 2# - acetoxypropropyl]quinolines which is cyclized to the required compounds. Diasteromeric 2,8 - bis(trifluoromethyl) - 4 - [3 - (3(R) - ethyl - 4(S) - piperidyl) - 1#,2#- oxapropylquinolines are prepared by reacting 2,8-bis(trifluoromethyl)-lepidine with a lithium compound followed by N-benzoyl-cincholoipan ethyl ester to yield 2,8-bis(trifluoromethyl) - 4- [3 - (1 - benzoyl - 3(R) - ethyl - 4(S) - piperidyl)- 2 - oxopropyl] - quinoline which is brominated under free radical conditions to yield a mixture of epimine 2,8-bis(trifluoromethyl)-4- [3 - (1 - benzoyl) - 3(R) - ethyl - 4(S) - piperidyl)- 1# - bromo - 2 - oxopropyl] - quinolines which are cyclized to a mixture of diastereomeric 2,8- bis(trifluoromethyl)- 4 - [3 - (1 - benzoyl - 3(R)- ethyl - 4(S) - piperidyl) - 1#,2# - oxapropyl]- quinolines which are reduced to the required compounds. Pharmaceutical compositions of the compounds I and II with the usual excipients show antimalarial activity when administered orally parenterally or rectally.
GB5284374A 1973-12-07 1974-12-06 Cinchonidine and cinchonidine derivatives Expired GB1441519A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US42264573A 1973-12-07 1973-12-07

Publications (1)

Publication Number Publication Date
GB1441519A true GB1441519A (en) 1976-07-07

Family

ID=23675777

Family Applications (1)

Application Number Title Priority Date Filing Date
GB5284374A Expired GB1441519A (en) 1973-12-07 1974-12-06 Cinchonidine and cinchonidine derivatives

Country Status (17)

Country Link
JP (1) JPS5088076A (en)
AT (2) AT339310B (en)
BE (1) BE823023A (en)
BR (1) BR7410249A (en)
CA (1) CA1039283A (en)
CH (1) CH605916A5 (en)
DE (1) DE2458146A1 (en)
DK (1) DK141700B (en)
FR (1) FR2292476A1 (en)
GB (1) GB1441519A (en)
IL (1) IL46181A (en)
KE (1) KE2718A (en)
MY (1) MY7700239A (en)
NL (1) NL7415931A (en)
PH (1) PH10837A (en)
SE (1) SE415100B (en)
ZA (1) ZA747664B (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2381044A1 (en) * 1977-02-17 1978-09-15 Hoffmann La Roche PROCESS FOR THE PREPARATION OF MEFLOQUINE
HU191508B (en) * 1982-12-02 1987-02-27 Alkaloida Vegyeszeti Gyar,Hu Process for preparing new chloromethyl-quinoline derivatives
HU188235B (en) * 1982-12-11 1986-03-28 Alkaloida Vegyeszeti Gyar,Hu Process for producing fluoro-methyl-quinoline derivatives
AU9740998A (en) * 1997-09-08 1999-03-29 F. Hoffmann-La Roche Ag Piperidine derivatives against malaria
JP2002360830A (en) * 2001-06-04 2002-12-17 Heiwa Corp Stock ball prize winning device

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1217427A (en) * 1967-12-21 1970-12-31 America Home Products Corp Cinchona alkaloid derivatives
CH590275A5 (en) * 1970-03-16 1977-07-29 Hoffmann La Roche
CH565792A5 (en) * 1971-01-07 1975-08-29 Hoffmann La Roche

Also Published As

Publication number Publication date
SE415100B (en) 1980-09-08
BE823023A (en) 1975-06-06
PH10837A (en) 1977-09-09
JPS5088076A (en) 1975-07-15
MY7700239A (en) 1977-12-31
DK141700B (en) 1980-05-27
FR2292476B1 (en) 1979-05-18
AU7559274A (en) 1976-05-27
IL46181A0 (en) 1975-03-13
CA1039283A (en) 1978-09-26
DK637674A (en) 1975-07-28
ATA24577A (en) 1979-05-15
CH605916A5 (en) 1978-10-13
DE2458146A1 (en) 1975-06-12
FR2292476A1 (en) 1976-06-25
NL7415931A (en) 1975-06-10
KE2718A (en) 1977-07-15
ZA747664B (en) 1976-01-28
ATA977974A (en) 1977-02-15
AT339310B (en) 1977-10-10
AT353792B (en) 1979-12-10
DK141700C (en) 1980-12-08
SE7415160L (en) 1975-06-09
IL46181A (en) 1978-03-10
BR7410249A (en) 1976-06-29

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Legal Events

Date Code Title Description
PS Patent sealed [section 19, patents act 1949]
PCNP Patent ceased through non-payment of renewal fee