Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
  • C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
  • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
  • C07C45/46—Friedel-Crafts reactions
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
  • C07C49/782—Ketones containing a keto group bound to a six-membered aromatic ring polycyclic
  • C07C49/788—Ketones containing a keto group bound to a six-membered aromatic ring polycyclic with keto groups bound to a condensed ring system
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
  • C07C49/782—Ketones containing a keto group bound to a six-membered aromatic ring polycyclic
  • C07C49/792—Ketones containing a keto group bound to a six-membered aromatic ring polycyclic containing rings other than six-membered aromatic rings

Definitions

• R substituent when the R substituent is a lower alkyl group, ethyl, isobutyl and hexyl are preferred. When the R and/or R substituent is lower alkyl, methyl is preferred. When the R substituent is cycloalkyl, cyclohexyl is preferred and when the R substituent is lower alkanoyl, acetyl is preferred.
• formaldehyde is suitably provided in the form of a polymer thereof such as paraformaldehyde.
• this reaction is carried out using an acid addition salt, especially a hydrohalide salt such as the hydrochloride, of a compound of formula II and, in this case, it may be advisable to include in the reaction mixture a small amount of the acid corresponding to the acid addition salt used.
• suitable solvents include anhydrous ethers such as diethyl ether and tetrahydrofuran and where an alkali-metal borohydride is used suitable solvents include alkanols containing from 1 to 4 carbon atoms such as methanol and ethanol or dioxane or an aqueous solution thereof.
• Lithium aluminum hydride is the preferred alkali-metal aluminum hydride and sodium borohydride is the preferred alkali-metal borohydride.
• the compounds of formula I above wherein R signifies a lower alkanoyl group can be prepared by the introduction of this group into the corresponding compound of formula Ib above.
• the lower alkanoylation can be carried using conventional techniques, for example, using a lower alkanoyl halide such as acetyl chloride or propionyl bromide or an anhydride of an alkanoic acid containing up to 6 carbon atoms such as acetic anhydride.
• the lower-alkanoylation is carried out using an anhydride of an alkanoic acid containing up to 6 carbon atoms in the presence of a catalytic amount of a strong acid such as perchloric acid.
• the compounds of formula II above and their acid addition salts are known and can be prepared, for example, by reducing 1-methyl-6,7-dimethoxy-3,4-dihydro-isoquinoline and, where required, converting the product into an acid addition salt.
• ketone starting materials of formula III above are also known and can be prepared, for example, by reacting a compound of the genreal formula wherein R and R are as described above with a compound of the general formula wherein R is as described above under the conditions employed for a Friedel-Crafts reaction.
• a preferred class of ketone starting materials include those compounds of formula III in which R, and R each represent lower alkyl.
• the isoquinoline derivatives provided by the invention can occur in racemic and optically active form and that the invention includes within its scope both the racemic and the optically active forms.
• a racemate can, if desired, be separated into its optical isomers in accordance with conventional methods, for example, by fractional crystallization of its salts formed with optically active acids.
• the optical isomers can, however, also be obtained by using an optically active starting material of formula II or by resolving an appropriate intermediate obtained during the process.
• the compounds of formula I above and the pharmaceutically acceptable acid addition salts thereof can be used as medicaments in the form of pharmaceutical preparation which contain them in association with a compatible pharmaceutical carrier.
• the carrier material may be an organic or inorganic inert carrier material which is suitable for enteral (e.g. oral) or parenteral administration. Examples of such carrier materials are water, gelatin, starch, talc, magnesium stearate, lactose and polyalkylene glycols.
• the pharmaceutical preparations can be made up in solid form (e.g. tablets, dragees and capsules) or in liquid form (e.g. solutions, suspensions and emulsions).
• EXAMPLE 4 (A) The preparation of the starting material 4-(2-cyclohexyl-acetyl)-1,2-dimethyl-benzene was prepared from 107 g. of 2-cyclohexyl-acetyl chloride, 94 g. of aluminum chloride and 70 g. of ortho-xylene in dichloromethane by a procedure analogous to that described in part A of Example 1.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)
• Other In-Based Heterocyclic Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=10477318

Family Applications (1)

Country Status (24)

Cited By (1)

• 1970
  • 1970-11-30 GB GB5670270A patent/GB1313017A/en not_active Expired
• 1971
  • 1971-11-01 ZA ZA717308A patent/ZA717308B/xx unknown
  • 1971-11-01 EG EG480/71A patent/EG10512A/xx active
  • 1971-11-02 IL IL38066A patent/IL38066A0/xx unknown
  • 1971-11-03 AU AU35297/71A patent/AU454027B2/en not_active Expired
  • 1971-11-05 CH CH1612571A patent/CH559725A5/xx not_active IP Right Cessation
  • 1971-11-11 DE DE19712156049 patent/DE2156049A1/de active Pending
  • 1971-11-19 BR BR7706/71A patent/BR7107706D0/pt unknown
  • 1971-11-22 US US00203100A patent/US3812133A/en not_active Expired - Lifetime
  • 1971-11-23 CS CS8160A patent/CS164916B2/cs unknown
  • 1971-11-24 RO RO68853A patent/RO60141A/ro unknown
  • 1971-11-26 DD DD159187A patent/DD95232A5/xx unknown
  • 1971-11-26 NL NL7116272A patent/NL7116272A/xx unknown
  • 1971-11-27 BG BG019118A patent/BG20355A3/xx unknown
  • 1971-11-29 AT AT1024271A patent/AT317215B/de not_active IP Right Cessation
  • 1971-11-29 DK DK583771AA patent/DK129236B/da unknown
  • 1971-11-29 BE BE775949A patent/BE775949A/xx unknown
  • 1971-11-29 SE SE7115274A patent/SE374110B/xx unknown
  • 1971-11-29 ES ES397454A patent/ES397454A1/es not_active Expired
  • 1971-11-30 SU SU1721026A patent/SU453837A3/ru active
  • 1971-11-30 FI FI713419A patent/FI49605C/fi active
  • 1971-11-30 HU HUHO1436A patent/HU162419B/hu unknown
  • 1971-11-30 FR FR7142902A patent/FR2115493B1/fr not_active Expired
• 1974
  • 1974-12-31 MY MY197444A patent/MY7400044A/xx unknown

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