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WO2010071117A1 - Procédé de fabrication de (s)-1-phényl-1,2,3,4-tétrahydroisoquinoléine - Google Patents

Procédé de fabrication de (s)-1-phényl-1,2,3,4-tétrahydroisoquinoléine Download PDF

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Publication number
WO2010071117A1
WO2010071117A1 PCT/JP2009/070853 JP2009070853W WO2010071117A1 WO 2010071117 A1 WO2010071117 A1 WO 2010071117A1 JP 2009070853 W JP2009070853 W JP 2009070853W WO 2010071117 A1 WO2010071117 A1 WO 2010071117A1
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phenyl
tetrahydroisoquinoline
anion
salt
optically active
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Japanese (ja)
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耕平 森
章 西山
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Kaneka Corp
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Kaneka Corp
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    • 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
    • C07D217/10—Quaternary compounds

Definitions

  • the present invention relates to a process for producing (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline useful as a pharmaceutical intermediate.
  • An object of the present invention is to provide a method for efficiently and inexpensively producing (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline having high optical purity.
  • the process for producing (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline with improved optical purity comprises (R) -1-phenyl-1,2,3,4-tetrahydro.
  • the following formula (1) containing isoquinoline as an impurity A salt is formed from (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline represented by the following formula and a non-optically active acid, followed by crystallization to give the following formula (2a):
  • a n ⁇ represents a non-optically active carboxylate anion, a non-optically active sulfonate anion, a non-optically active phosphonate anion, a chloride anion (Cl ⁇ ), a bromide anion (Br ⁇ ), a nitrate anion.
  • the n is preferably 1.
  • the non-optically active acid is preferably acetic acid or p-toluenesulfonic acid.
  • (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline represented by the formula (especially containing (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline as an impurity ( S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline), which is represented by the following formula (3):
  • a salt is precipitated from racemic 1-phenyl-1,2,3,4-tetrahydroisoquinoline and L-tartaric acid represented by formula (I), and the resulting mother liquor is treated with a base.
  • the present invention provides the following formula (2b):
  • B ⁇ represents a non-optically active carboxylate anion or a non-optically active sulfonate anion.
  • S -1-phenyl-1,2,3,4-tetrahydro Also related to isoquinoline salts.
  • B - is acetate anion, such as p- toluenesulfonate anion are preferred.
  • Example 1 is an X-ray powder analysis spectrum of (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / acetate obtained in Example 7.
  • FIG. The vertical axis represents the X-ray intensity (cps), and the horizontal axis represents the diffraction angle (2 ⁇ ).
  • S-form material (S) -1-phenyl-1,2,3 containing (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline, which is a starting material of the present invention, as an impurity , 4-Tetrahydroisoquinoline (hereinafter sometimes referred to as “S-form material”) will be described.
  • S-form material examples include (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline and (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline, A mixture in which (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline is in excess of (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline can be used.
  • optical purity of (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline in the S-form raw material is, for example, 60 to 90% e. e. Degree, preferably 70-90% e.e. e. Degree, more preferably 80-85% e.e. e. Degree.
  • the method for producing or obtaining the S-form material is not particularly limited.
  • 1-phenyl-3,4-dihydroisoquinoline is hydrogenated in the presence of an optically active ruthenium catalyst.
  • the method of making it According to this method, about 60-90% e. e. (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline can be obtained.
  • racemic raw material A racemic 1-phenyl-1,2,3,4-tetrahydroisoquinoline represented by the formula (hereinafter sometimes referred to as “racemic raw material”) is brought into contact with L-tartaric acid in the presence of a solvent, and a precipitate ( Usually a salt formed from a racemic raw material and L-tartaric acid, referred to herein as (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / L-tartrate, In some cases, it is abbreviated as “body tartrate. Preferably, it is a crystal of the salt”, and then the resulting mother liquor is treated with a base, and this method is preferably used.
  • the amount of L-tartaric acid is, for example, about 0.3 to 2 mol, preferably about 0.5 to 1.5 mol, more preferably about 0.8 to 1.2 mol, with respect to 1 mol of the racemic raw material. is there.
  • the solvent examples include water and water-soluble organic solvents (especially alcohols such as methanol and ethanol), and these may be used alone or in combination.
  • a preferred solvent is C 1-2 alcohol or a mixed solvent of C 1-2 alcohol and water.
  • the volume ratio water / C 1-2 alcohol
  • the volume ratio is 50/50 or less, preferably 1/99 to 30/70, more preferably 5/95 to 20 / 80 or so.
  • the contact procedure of the racemic raw material and L-tartaric acid is not particularly limited, but usually, both the racemic raw material and L-tartaric acid are separately dissolved in a solvent, and then one is added to the other.
  • the racemic raw material solution is added to the L-tartaric acid solution.
  • the R-form tartrate is formed and precipitated as described above.
  • the mixing temperature and time can be appropriately set according to the solvent to be used, but are, for example, ⁇ 10 to 30 ° C. and 1 hour or longer.
  • the target S body material is dissolved in the mixed solution.
  • an S form raw material solution can be obtained.
  • This S-form material solution may be used as a starting material as it is, but it is usually used as a concentrated oil or solid after appropriate post-treatment such as base treatment, concentration, washing and solidification (crystallization). .
  • alkali such as sodium oxide, potassium hydroxide, sodium carbonate, potassium carbonate
  • the amount of alkali is not particularly limited, but may be, for example, about 0.5 to 10 moles per mole of the racemic raw material.
  • an S-form material is precipitated. This precipitate may be recovered by filtration as it is, or may be extracted and recovered by adding an organic solvent such as toluene, ethyl acetate, methyl tert-butyl ether or the like.
  • the optical purity of the S-form material thus obtained is about 70 to 90% e.e. e. Degree, preferably 75-88% e.e. e. Degree, more preferably 80-85% e.e. e. Degree.
  • S form salt crystal (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline salt crystal (hereinafter referred to as “S form salt crystal”). ) To improve its optical purity.
  • the S-form salt crystal has the following formula (2a): It is represented by Here, in the formula (2a), A n-non optically active carboxylate anions, non-optically active sulfonate anions, non-optically active phosphonate anion, chloride anion, bromide anion, nitrate anion, hydrogen sulfate anion, Or it represents a perchlorate anion. N in A n- represents the valence of the anion.
  • non-optically active carboxylate anion examples include, for example, formate anion, acetate anion, cyanoacetate anion, dichloroacetate anion, trifluoroacetate anion, propionate anion, butanoate anion, isobutanoate Anion, pivalate anion, phenylacetate anion, benzoate anion, acrylate anion, cinnamate anion, oxalate anion, malonate anion, adipate anion and the like.
  • non-optically active sulfonate anion examples include methanesulfonate anion, trifluoromethanesulfonate anion, ethanesulfonate anion, benzenesulfonate anion, p-toluenesulfonate anion, p-chlorobenzenesulfonate anion, p-nitrobenzenesulfonate anion, and the like. Can be mentioned.
  • a n- is such preferably non-optically active carboxylate anions, non-optically active sulfonate anions.
  • N is preferably 1.
  • the salt crystals formed by these preferred anions can be represented by the following formula (2b), and this compound is a novel compound not described in any literature.
  • B ⁇ represents a non-optically active carboxylate anion or a non-optically active sulfonate anion
  • the most preferred A n- and B - is acetate anion, a p- toluenesulfonate anion, more preferably an acetate anion.
  • the S-form salt crystal can be produced by forming a salt from the S-form material and a non-optically active acid (achiral acid) and crystallization.
  • non-optically active acid examples include a non-optically active carboxylate anion, a non-optically active sulfonate anion, a non-optically active phosphonate anion, a chloride anion, a bromide anion, a nitrate anion, a hydrogen sulfate anion, or a perchlorate anion.
  • a non-optically active carboxylate anion examples include a non-optically active carboxylate anion, a non-optically active sulfonate anion, a non-optically active phosphonate anion, a chloride anion, a bromide anion, a nitrate anion, a hydrogen sulfate anion, or a perchlorate anion.
  • acids include inorganic acids such as hydrogen chloride, hydrogen bromide, sulfuric acid, nitric acid, perchloric acid, and phosphoric acid; formic acid, acetic acid, cyanoacetic acid, dichloroacetic acid, trifluoroacetic acid, propionic acid, butyric acid, Carboxylic acids such as isobutyric acid, pivalic acid, phenylacetic acid, benzoic acid, acrylic acid, cinnamic acid, oxalic acid, malonic acid, adipic acid; methanesulfonic acid, trifluoromethanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p- Examples thereof include sulfonic acids such as toluenesulfonic acid, p-chlorobenzenesulfonic acid, and p-nitrobenzenesulfonic acid. From the viewpoint of obtaining a compound with high optical purity, acetic acid,
  • the amount of the non-optically active acid used is, for example, about 0.5 to 10 mol, preferably about 0.9 to 7 mol, and more preferably about 1 to 5 mol, relative to 1 mol of the S-form material. Yes, it may be about 0.8 to 1.5 moles.
  • a solvent When the acid and the S-form material are mixed, a solvent is usually used.
  • the solvent include water; alcohol solvents such as methanol, ethanol and isopropanol; ether solvents such as tetrahydrofuran, 1,4-dioxane, ethylene glycol dimethyl ether and methyl tert-butyl ether; ester solvents such as ethyl acetate and isopropyl acetate; Hydrocarbon solvents such as benzene, toluene, xylene and hexane; ketone solvents such as acetone and methyl ethyl ketone; nitrile solvents such as acetonitrile, propionitrile and benzonitrile; halogen solvents such as methylene chloride, chloroform and chlorobenzene; N Amide solvents such as N, N-dimethylformamide and N, N-dimethylacetamide; sulfoxide solvents such as
  • the mixing ratio when using two or more solvents in combination is not particularly limited.
  • Preferable examples include methyl tert-butyl ether, ethyl acetate, toluene, and hexane.
  • the amount of the solvent used is not particularly limited, but too much is not preferable in terms of cost and post-treatment. Therefore, the amount of the solvent used is preferably 50 parts by mass or less, more preferably 20 parts by mass or less, with respect to 1 part by mass of the S-form material.
  • a method of crystallizing a salt of S form by mixing the S form raw material with a non-optically active acid in a solvent.
  • B A method in which the S-form raw material and a non-optically active acid are mixed in a solvent and then cooled to crystallize the salt of the S-form.
  • C A method of crystallizing a salt of S form by mixing the S form raw material and a non-optically active acid in a solvent and then adding a poor solvent such as hexane.
  • (D) A method of crystallizing a salt of S form by mixing the S form raw material and a non-optically active acid in a solvent and then concentrating under reduced pressure.
  • (E) A method of crystallizing a salt of S form by mixing the S form raw material and a non-optically active acid in a solvent and then concentrating and replacing with a poor solvent such as hexane.
  • crystallization can be performed by appropriately combining the methods (a) to (e).
  • a seed crystal may be added in the crystallization of the salt of the S form.
  • the optical purity can be increased by performing recrystallization such as cooling and crystallization by heating and dissolving the S-form salt crystal in a solvent.
  • the operating temperature in the method for crystallizing the S-form salt of (a) to (e) is not particularly limited, but may be appropriately selected depending on the type of salt and the type of solvent used, preferably the type of solvent used or the mixture It is preferable to set the solvent species according to the target precipitation amount and crystal quality at a temperature lower than the temperature at which the total amount of the S-form salt crystals dissolves.
  • the S-form salt crystals precipitated by the crystallization methods (a) to (e) can be separated and obtained by a method such as vacuum filtration, pressure filtration, or centrifugation. Further, when the mother liquor remains in the acquired crystal and the purity of the crystal is lowered, the quality can be improved by further washing with a solvent as necessary.
  • the S-form salt crystals obtained as described above are usually dried. There are no particular restrictions on the method for drying the crystals, but it is preferable to dry under reduced pressure (vacuum drying) at about 60 ° C. or less, avoiding thermal decomposition and melting of the S-form salt crystals.
  • the optical purity of the S-form salt crystal thus obtained is, for example, + 5% e. e. Or more, preferably + 10% e.e. e. Or more, more preferably + 15% e.e. e. It has been improved.
  • the optical purity of the S-form salt crystal is, for example, 75% e.e. e. Or more, preferably 80% e.e. e. Or more, more preferably 95% e.e. e. That's it. 99% e.e. by optimizing crystallization conditions. e. It is also possible to obtain the above S-form salt crystals.
  • S-form purified product is obtained by treating the S-form salt crystals obtained as described above with a base.
  • This S-form purified product has an optical purity equivalent to that of the S-form salt crystal, and there is no decrease in optical purity due to the base treatment of the S-form salt crystal.
  • the S-form salt crystal When the S-form salt crystal is treated with a base, the S-form salt crystal is preferably dissolved in water, and then the base is added.
  • the water may be in an amount sufficient to dissolve a part of the S-form salt crystals and react with the base.
  • the amount of water used is preferably 50 parts by mass or less, and more preferably 5 to 20 parts by mass with respect to 1 part by mass of S-form salt crystals.
  • Examples of the base include metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide, and magnesium hydroxide (particularly alkali metal or alkaline earth metal hydroxide); sodium carbonate, potassium carbonate, magnesium carbonate, and the like.
  • Metal carbonates especially alkali metal or alkaline earth metal carbonates
  • metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate (particularly alkali metal or alkaline earth metal hydrogen carbonates); ammonia, triethylamine, etc. Examples of the amines can be exemplified.
  • the base is preferably sodium hydroxide or potassium hydroxide from an economical viewpoint.
  • the amount of the base used is determined based on the pH of water.
  • the pH of the water after the base treatment is, for example, 7 or more, preferably about 10 to 13.
  • the amount of the base used can be appropriately set within this pH range.
  • the amount is preferably 0.5 to 20 mol, more preferably 1 to 5 mol, per 1 mol of the S-form salt crystal.
  • the base dissolved in water may be used.
  • the purified S-form obtained by removing the salt in this manner is recovered from the base treatment solution by an appropriate method.
  • the recovery method include a method in which an organic solvent such as ethyl acetate, toluene, or methyl tert-butyl ether is added for extraction, and the solvent is distilled off by an operation such as heating under reduced pressure.
  • separating acquisition is more preferable.
  • Examples of the method for precipitating crystals include a method of slowly adding a base to the aqueous solution of the S-form salt crystals.
  • an organic solvent compatible with water such as methanol, ethanol, isopropanol, acetone, and acetonitrile, may be further added.
  • Examples of the method for separating crystals of the purified S-form include vacuum filtration, pressure filtration, or centrifugation. Further, when the mother liquor remains in the acquired crystal and the purity of the crystal is lowered, the quality can be improved by further washing with a solvent as necessary.
  • the S-form purified product obtained as described above is usually dried. Although there is no restriction
  • Example 1 Production of S Form Raw Material
  • a solution consisting of 1726 mg (11.5 mmol, 1 equivalent) of L-tartaric acid and 10 mL of methanol 2750 mg of racemic 1-phenyl-1,2,3,4-tetrahydroisoquinoline (racemic raw material)
  • a methanol solution (10 mL) having a chemical purity of 87.4% by mass and 11.5 mmol was added dropwise and cooled to 5 ° C., crystals were precipitated.
  • the precipitated (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / L-tartaric acid salt crystals (R-form tartrate crystals) were removed by vacuum filtration.
  • Example 2 Production of S-form salt crystals (acetate) 82% e.e. produced in Example 1. e. Into an ethyl acetate solution (6 mL) of 848 mg (chemical purity 93 mass%, (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline pure content 780 mg, 3.7 mmol) of 200 mg of acetic acid (3.3 mmol, 0.9 eq) was added and warmed to 60 ° C. When hexane (8 ml) was added and cooled to 25 ° C., crystals were precipitated.
  • Example 3 Production of S Form Purified Product 647 mg of S form salt crystals produced in Example 2 (chemical purity 98.9% by mass, (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / acetic acid Pure salt (640 mg, 2.4 mmol) and water (8 ml) were mixed and cooled to 5 ° C. 640 mg (4.8 mmol, 2 equivalents) of a 30% by mass aqueous sodium hydroxide solution was added, and the mixture was stirred for 4 hours while raising the temperature from 5 ° C to 25 ° C.
  • Example 4 Preparation of S-form salt crystal (acetate) L-tartaric acid 751 mg (5.0 mmol, 1 equivalent) was added to a solution of 1 mL of water and racemic 1-phenyl-1,2,3,4-tetrahydroisoquinoline ( Racemic raw material) 1197 mg (chemical purity 87.4% by mass, 5 mmol) of ethanol solution (9 mL) was added dropwise and cooled to 5 ° C. to precipitate crystals. After stirring for 1 hour, the precipitated (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / L-tartaric acid salt crystals (R-form tartrate) were removed by vacuum filtration.
  • the salt crystals were washed with 3 mL of ethanol, and the washing solution was added to the mother liquor.
  • the optical purity of (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline in the mother liquor obtained was measured, it was 84% e. e. Met.
  • 10 mL of water was added here, and ethanol was distilled off under reduced pressure.
  • 10 mL of toluene was added, and a 30% by mass aqueous sodium hydroxide solution was further added until pH 13 was reached. After the aqueous layer was separated, the organic layer was washed with 5 mL of saturated brine and concentrated under reduced pressure to obtain a colorless oil (S body raw material).
  • Example 5 Preparation of S-form salt crystal (acetate) L-tartaric acid (751 mg, 5.0 mmol, 1 equivalent) and a solution of 1 mL of water were mixed with racemic 1-phenyl-1,2,3,4-tetrahydroisoquinoline ( When 1197 mg (87.4% by mass, 5 mmol) of an ethanol solution (9 mL) was added dropwise and cooled to 5 ° C., crystals were precipitated. After stirring for 1 hour, the precipitated (R) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / L-tartaric acid salt crystals (R-form tartrate) were filtered under reduced pressure and washed with 3 mL of ethanol. .
  • Example 7 The X-ray crystallographic spectrum of (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / acetate prepared in Example 2 is shown in FIG. 2 ⁇ is about 8.9 °, 11.0 °, 13.0 °, 13.7 °, 15.8 °, 17.9 °, 19.1 °, 20.0 °, 21.5 °, 23. The most prominent peaks were seen in XRD at 4 ° and 26.7 °.
  • X-ray powder crystal analyzer MiniFlex-ll manufactured by Rigaku Corporation Measurement conditions: CuK ⁇ 1 wire Tube voltage 30 kV Current between 15 mA
  • Example 8 The (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline / p-toluenesulfonate prepared in Example 6 was analyzed by X-ray crystal in the same manner as in Example 7. At 2 ⁇ of about 8.7 °, 9.7 °, 11.0 °, 17.1 °, 17.5 °, 19.0 °, 19.9 °, 20.4 °, and 21.6 °, The most prominent peak was seen in XRD.
  • the present invention is useful for increasing the optical purity of (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline.
  • This (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline is useful as a pharmaceutical intermediate.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Selon l'invention, par la formation d'un sel à partir d'un acide non optiquement actif et de la (S)-1-phényl-1,2,3,4-tétrahydroisoquinoléine représentée par la formule (1) : (1) qui comporte la (R)-1-phényl-1,2,3,4-tétrahydroisoquinoléine en tant qu'impureté, et par la  cristallisation, sont fabriqués des cristaux de sel de (S)-1-phényl-1,2,3,4-tétrahydroisoquinoléine qui est représentée par la formule (2a) : (2a) (dans la formule (2a), An- représente un anion carboxylate non optiquement actif, un anion sulfonate non optiquement actif, un anion phosphonate non optiquement actif, un anion chlorure, un anion bromure, un anion nitrate, un anion hydrogénosulfate ou un anion perchlorate, le n de An- représentant la valence de l'anion). Puis, par le traitement des cristaux de sel par une base, la (S)-1-phényl-1,2,3,4-tétrahydroisoquinoléine est fabriquée.
PCT/JP2009/070853 2008-12-15 2009-12-14 Procédé de fabrication de (s)-1-phényl-1,2,3,4-tétrahydroisoquinoléine Ceased WO2010071117A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001288171A (ja) * 2000-04-10 2001-10-16 Sumitomo Chem Co Ltd 光学活性テトラヒドロイソキノリン誘導体の製造方法
WO2008019055A2 (fr) * 2006-08-03 2008-02-14 Teva Pharmaceutical Industries Ltd. Procédé de dédoublement optique de 1-phényl-1,2,3,4-tétrahydroisoquinoléine

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* Cited by examiner, † Cited by third party
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CN1204130C (zh) * 2002-11-22 2005-06-01 中国科学院成都有机化学研究所 光学纯四氢呋喃－2－甲酸制备工艺

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001288171A (ja) * 2000-04-10 2001-10-16 Sumitomo Chem Co Ltd 光学活性テトラヒドロイソキノリン誘導体の製造方法
WO2008019055A2 (fr) * 2006-08-03 2008-02-14 Teva Pharmaceutical Industries Ltd. Procédé de dédoublement optique de 1-phényl-1,2,3,4-tétrahydroisoquinoléine

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
"1, 2, 3, 4-Tetrahydro-I-phenylisoquinoline (IQL base racemate) and 1, 2, 3, 4-tetrahydro- 1-phenylisoquinoline oxalate salt (IQL-oxalate racemate), (No. IPCOM000139416D)", IP.COM JOURNAL, vol. 6, no. 9A, 24 August 2006 (2006-08-24), pages 10 *
HIROYUKI NOHIRA: "Shizen Bunsho no Joken to Jitsuyorei", KABAKU ZOKAN 97 'FUSEI GOSEI TO KOGAKU BUNKATSU NO SHINPO', 15 October 1982 (1982-10-15), pages 165 - 174 *
KAZUHIKO SAIGO: "3.Yusen Shoshutsuho", KIKAN KAGAKU SOSETSU NO.6 'KOGAKU ISEITAI NO BUNRI', 10 June 1999 (1999-06-10), pages 32 - 44 *
LUDWIG, M. ET AL.: "Affinity of 1-aryl-1, 2, 3, 4-tetrahydroisoquinoline derivatives to the ion channel binding site of the NMDA receptor complex", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 41, no. 8, 2006, pages 1003 - 1010 *
NAITO, R. ET AL.: "Synthesis and Antimuscarinic Properties of Quinuclidin-3-yl 1, 2, 3, 4- Tetrahydroisoquinoline-2-carbxylate Derivatives as Novel Muscarinic Receptor Antagonists", JOURNAL OF MEDICINAL CHEMISTRY, vol. 48, 2005, pages 6597 - 6606 *

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