Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D457/00—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid
  • C07D457/04—Heterocyclic compounds containing indolo [4, 3-f, g] quinoline ring systems, e.g. derivatives of ergoline, of the formula:, e.g. lysergic acid 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 in position 8

Definitions

• the invention relates to N-substituted 9,10-dihydrolysergic acid esters and a process for their preparation.
• X represents a hydrogen or halogen atom
• the alkyl group is simultaneously introduced into the 1-position of the compound of the general formula II and the group in the 8-position is esterified or transesterified by the same alkyl group which was introduced into the 1-position.
• R represents a hydrogen atom or an organic radical which can be hydrolyzed in an alkaline medium. Therefore, those 9,10-dihydrolysergic acid esters in which R represents any organic radical of higher molecular weight can also be used for the process according to the invention than the introduced group R is.
• This organic radical R is the intermediate alkaline Hy drolysis replaced by a lower group R.
• the compounds of the general formulas 11 and 111 are known and described or can be prepared by processes known per se.
• Tetrabutylammonium bromide, tetrabutylammonium hydrogen sulfate, triethylbenzylammonium chloride, tricaprylmethylammonium chloride or tetrabutylphosphonium bromide, for example, can be used as the catalyst for phase transfer.
• the phase transfer catalyst is used in an amount of 0.1 to 3 moles to 1 mole of 9,10-dihydrolysergic acid.
• the amount of catalyst within these limits greatly affects the rate of the reaction. Since 9,10-dihydrolysergic acid and its derivatives are very sensitive compounds, a rapid course of the reaction is desirable. Therefore, the use of the catalyst in an amount close to the above upper limit is advantageous.
• the water-immiscible inert organic solvent can e.g. Benzene, toluene, xylene or a saturated hydrocarbon such as pentane, hexane, heptane or cyclohexane.
• the alkaline aqueous phase is a 20-50% aqueous alkali hydroxide solution, e.g. Caustic soda.
• the inventive method is carried out at room temperature or moderately elevated temperature.
• the substitution of the 9,10-dihydrolysergic acid derivatives in the 8-position is faster than in the 1-position. Therefore, the esters and the N-substituted esters can be isolated from the reaction mixture at the beginning of the reaction. By continuing the reaction, the concentration of the ester is reduced until it completely disappears at the end of the reaction and only the N-substituted ester is obtained.
• alkyl, alkenyl or cycloalkyl group is introduced into a 9,10-dihydrolysergic acid alkyl, alkenyl or cycloalkyl ester according to the invention, a 1- (alkyl or alkenyl or cycloalkyl) - 9,10-dihydrolysergic acid alkyl, alkenyl or cycloalkyl esters can be obtained.
• the compounds according to the invention are important intermediate compounds for the synthesis of therapeutically highly effective compounds with an N-substituted group in the 1-position.
• the further reactions of the synthesis proceed primarily in the direction of reducing the ester group in the 8-position to the primary alcohol group, into which a suitable acid residue, e.g. the 5-bromnicotinic acid residue is introduced. Therefore, the simultaneous introduction of the R group in the 1-position and the esterification of the carboxy group in the 8-position, which are thereby for the reduction in. the alcohol group becomes more accessible, very advantageous.
• the toluene extract is separated from the aqueous phase and then the aqueous phase is extracted twice with 200 ml of toluene and 0.63 g (5 mmol) of dimethyl sulfate.
• the combined toluene extracts are washed with water and evaporated to dryness in vacuo. There will be 2.14 g or 71.8% of theory Th. Crystalline 1-methyl-9,10-dihydrolysergic acid methyl ester obtained.
• the compound has the properties given in Example 1.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (2)

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Family Applications (1)

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• 1977
  • 1977-07-21 YU YU1819/77A patent/YU40004B/xx unknown
• 1978
  • 1978-06-29 FI FI782081A patent/FI64369C/fi not_active IP Right Cessation
  • 1978-07-06 AT AT0490078A patent/AT363195B/de not_active IP Right Cessation
  • 1978-07-07 US US05/922,692 patent/US4230859A/en not_active Expired - Lifetime
  • 1978-07-12 PT PT68278A patent/PT68278A/pt unknown
  • 1978-07-14 ES ES471716A patent/ES471716A1/es not_active Expired
  • 1978-07-18 CS CS784790A patent/CS216231B2/cs unknown
  • 1978-07-18 DE DE7878100419T patent/DE2860896D1/de not_active Expired
  • 1978-07-18 EP EP78100419A patent/EP0000533B1/de not_active Expired
  • 1978-07-20 SU SU782637592A patent/SU784775A3/ru active
  • 1978-07-21 JP JP8850978A patent/JPS5436296A/ja active Granted

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