WO2006022311A1 - アゾ化合物とその製造方法 - Google Patents
アゾ化合物とその製造方法 Download PDFInfo
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- WO2006022311A1 WO2006022311A1 PCT/JP2005/015390 JP2005015390W WO2006022311A1 WO 2006022311 A1 WO2006022311 A1 WO 2006022311A1 JP 2005015390 W JP2005015390 W JP 2005015390W WO 2006022311 A1 WO2006022311 A1 WO 2006022311A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Definitions
- the present invention relates to an aromatic azo compound having a diazo group at the 5-position of 2,3_dihydrobenzofuran, and 2,3_dihydrobenzazofuran having an amino group or a condensed cyclic amino group at the 5-position. _ It relates to a method for producing dihydrobenzofuran derivatives.
- a compound having a substituted amino group at the 5-position of the 2,3-dihydrobenzofuran ring is an important compound as a raw material for pharmaceuticals, since many compounds have useful physiological activities.
- Patent Document 2 discloses bromination of the 5-position of 2,3-dihydrobenzobenzofuran, reaction with benzylamine to replace bromine with a pendinoleamino group, and subsequent catalytic reduction to remove the pendinoleamino group.
- a method for introducing an amino group at the 5-position of 2,3-dihydrobenzofuran is disclosed.
- Patent Document 1 International Publication No. 00/34262 Pamphlet
- Patent Document 2 Japanese Patent Laid-Open No. 2003-104981
- Patent Document 3 International Publication Pamphlet 98/08842
- Non-Patent Document 1 Tetrahedron: Asymmetry 10 (1999) 1521-1526
- the present invention provides an aromatic azo compound having a diazo group at the 5-position of a 2,3-dihydrobenzofuran ring, and an amino group or isoindoleyl at the 5-position from the raw material.
- the purpose of the present invention is to provide a new and efficient production method suitable for industrial production of 2,3-dihydrobenzofuran derivatives having a group.
- the present inventors have conducted a diazo coupling reaction between a benzene diazonium salt having an electron withdrawing group and a 2,3-dihydrobenzofuran derivative. It was found that the reaction proceeds in high yield when carried out in a mixed solvent of water and a predetermined polar organic solvent, and the present invention has been completed.
- the present invention provides:
- ring A has at least one electron-withdrawing group in addition to the diazo group, and an optionally substituted benzene ring, X— represents an anion).
- R 1 and R 2 are the same or different, respectively.
- Anorekinore, R 3 is is substituted
- a reel that may have been R 5 and R 6 are the same or different and each represents a hydrogen atom, C alkyl, halogen, C alkoxy or C alkylthio)
- R 1 and R 2 are the same or different and each is alkyl, R 3 is substituted
- R 4 , R 5 and R 6 may be the same or different and each represents a hydrogen atom, C alkyl, halogen, C alkoxy or C alkylthio,
- R 7 , R 1Q and R 11 are the same or different and each represents a hydrogen atom, an optionally halogenated C alkyl, nitro, C alkoxysulfonyl, C alkoxysulfur.
- R 9 represents a halogen atom
- R 9 represents halogenated C alkyl, nitro, C alkoxysulfonyl
- diazo coupling reaction between a benzene diazonium salt having an electron withdrawing group and a 2,3-dihydrobenzofuran derivative is carried out between water and a certain polar organic solvent.
- an aromatic azo compound having a diazo group at the 5-position of the 2,3-dihydrobenzofuran ring can be quantitatively obtained.
- each compound may be a racemate or an optically active substance.
- the A ring represents an optionally substituted benzene ring having at least one electron withdrawing group in addition to the diazo group.
- the electron withdrawing group substituted on the A ring include halogenated C alkyl, nitro, C alkoxysulfo.
- Examples include rubamoyl and halogen atoms.
- the halogenated C alkyl includes trifluoromethyl, trifluoro
- Alkoxysulfonyl includes methoxysulfonyl, ethoxysulfonyl and the like.
- C Alkoxysulfenyl includes methoxysulfinyl, ethoxysulfinyl, etc.
- N, N DiC alkylaminosulfonyl includes N, N dimethylaminosulfonyl
- C alkyl carbonyl includes acetyl, propionyl, butyryl, isobutyryl
- C Alkoxycarbonyl includes methoxycarbonyl, ethoxycarbonyl, pro
- N, N Di C alkyl rubamoyl includes N, N dimethylcarbamoyl,
- halogen atom examples include fluorine, chlorine, bromine and iodine.
- nitro, C alkoxysulfonyl, etc. are preferred as electron withdrawing groups.
- the substitution position of is preferably the para-position and ortho-position of the A ring.
- the number of electron withdrawing groups is preferably 1 to 3.
- At least one electron withdrawing group other than a diazonium group, represented by A ring, and further substituted, may be, or may be benzene ring" in "A further substituted or may be Examples of the substituent of “R, benzene ring” include a C alkyl group.
- the benzene diazonium salt represented by the above formula (I) is an anion represented by X—.
- halogen anions eg, fluorine, chlorine, bromine, iodine
- tetrahalogenoborates eg, tetrafluoroborate
- R 1 and R 2 are the same or different and each represents C
- R 5 and R 6 are the same or different and each represents a hydrogen atom, C alkyl, halogen,
- C represents alkoxy or C alkylthio.
- C alkyl represented by R 1 or R 2 examples include methyl, ethyl, propyl,
- Examples of the “aryl group” in the “optionally substituted aryl group” represented by R 3 include phenyl, naphthyl and the like, and the “aryl group” in the “optionally substituted aryl group” is exemplified.
- substituents include: (1) halogen atoms (eg, fluorine, chlorine, bromine, iodine, etc.), (2) C alkylene dioxy (eg, methylenedioxy, ethylenedioxy, etc.)
- Halogenated may, C alkyl, (6) Halogenated
- C arylenoyl eg, phenolic, 1
- C 1 -alkyl is preferable.
- aryl group means that each substituent is substituted when the number of substituents which may have, for example, 1 to 5, preferably:! May be the same or different.
- Examples of the “optionally halogenated C alkyl” include 1 to 5, preferably
- C alkyl eg, methinole, ethyl, propyl, isopropylinole, butyl, isobutyl, sec-
- halogen atoms eg, fluorine, chlorine, bromine, iodine, etc.
- C alkenyl eg, vinyl, aranole, isopropenyl, butenyl, isobutenyl, sec ⁇
- halogen atoms eg, fluorine, chlorine, bromine, iodine, etc.
- Butenyl and the like include biel, aryl, isopropenyl, butenyl, isobutenyl, sec-butenyl, 3,3,3-trifluoro-1-propenyl, 4,4,4 trifluoro-1-butenyl, and the like.
- Examples of the “optionally halogenated C alkynyl” include 1 to 5, preferably
- C alkynyl eg, etul, propargyl, butur, 1_hexyl, etc.
- halogen atoms eg, fluorine, chlorine, bromine, iodine, etc.
- I can get lost.
- Specific examples include ethur, propargyl, buthur, 1_hexyl, 3,3,3_trifluoro-1_propynyl, 4,4,4_trifluoro_1-butul, and the like.
- C cycloalkyl eg, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexane
- 1 to 3 halogen atoms eg, fluorine, chlorine, bromine, iodine, etc.
- Specific examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4,4-dichlorocyclohexenole, 2,2,3,3 tetrafluorocyclopentyl, 4 chlorocyclohexyl and the like.
- C alkoxy eg, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutyl
- halogen atoms eg, fluorine, chlorine, bromine, iodine, etc.
- halogen atoms eg, fluorine, chlorine, bromine, iodine, etc.
- C alkylthio eg, methylthio, ethylthio, propylthio, isopropylthio
- Butylthio, sec-butylthio, tert-butylthio and the like Specific examples include methylthio, difluoromethylthio, trifluoromethylthio, ethylthio, propylthio, isopropylthio, butylthio, 4, 4, 4 trifluorobutylthio, pentylthio, hexylthio and the like.
- acyl for example, formyl, carboxy, rubamoyl, C alkyl
- C alkoxycarbonyl eg, methoxycarbonyl, ethoxycarbonyl
- 5- or 6-membered heterocyclic carboninole eg, nicotinol, isonicotinoyl, 2_thenoinole, 3_thenoinole, 2-fluoroinole, 3-fluoroinole, morpholinocarbonyl, thiomorpholinocarbonyl , Piperidinocarbonyl, 1 Pyrrolidinylcarbonyl, etc.
- rubamoyl eg, phenylcarbamoyl, 1_naphthylcarbamoyl, 2_naphthylcarbamoyl, etc.
- thiocarbamoyl eg, 5- or 6-membered heterocyclic rubamoyl (eg, 2-pyridylcarbamoyl, 3_pyridylcarbamoyl) , 4_pyridylcarbamoyl, 2—Cheylcarbamoyl, 3_Cheylcarbamoyl, etc.), C alkylsulfonyl (eg, phenylcarbamoyl, 1_naphthylcarbamoyl, 2_naphthylcarbamoyl, etc.), thiocarbamoyl, 5- or 6-membered heterocyclic rubamoyl (eg, 2-pyridylcarbam
- methylsulfonyl e.g., methylsulfonyl, ethylsulfonyl, etc.
- C arylsulfonyl e.g., phenyl
- Inyl eg, phenyl sulfier, 1_naphthyl sulfiel, 2_naphthyl sulfinyl, etc.
- acylamino examples include formylamino, C alkylcarbonylamino
- acetylamino acetylamino
- c-aryl carbonylamino e.g., phenylcarbonyl
- acyloxy for example, C alkylcarbonyloxy (for example, acetate
- aryl-force ruberamoyloxy eg, phenylcarbamoyloxy, naphthylcarb
- nicotinyloxy eg, nicotinyloxy and the like.
- Examples of the “substituent” of the “optionally substituted 5- to 7-membered saturated cyclic amino” include C alkyl (eg, methinole, ethyl, propyl, iso
- 10-membered aromatic heterocyclic group eg, 2_ or 3_ chenyl, 2—, 3_ or 4_ pyridinole, 2_, 3_, 4_, 5_ or f or 8_ quinolinole, 1 _ , 3 _, 4_ or f 5_ isoquinolinol, 1-, 2_ or 3 _ indolyl, 2_ benzothiazolyl, 2_ benzo [b] chenyl, benzo [b] furanyl, etc.) It is done.
- C alkyl represented by R 4 , R 5 or R 6 includes C 1 alkyl represented by R 1 or R 2
- halogen represented by R 4 , R 5 or R 6 examples include fluorine, chlorine, bromine and iodine.
- C alkoxy represented by R 4 , R 5 or R 6 includes methoxy, ethoxy, propoxy
- C alkylthio represented by R 4 , R 5 or R 6 includes methylthio, ethylthio,
- propylthio isopropylthio, butylthio, sec-butylthio, tert-butylthio and the like.
- R 4 , R 5 and R 6 are preferably C alkyl.
- R 7 , R 8 , R 1Q and R 11 are the same or different and each is a hydrogen atom, C halogenoquinole which may be halogenated, nitro, C alkoxysulfo
- Sulfonyl eg, N, N-dimethylaminosulfonyl, etc.
- cyan C alkyl-carbo
- Nyl eg, acetyl, propionyl, etc.
- c alkoxycarbonyl eg, methoxycal Bonyl, ethoxycarbonyl, etc.
- N, N di C alkyl rubamoyl eg, N, N
- Dimethylcarbamoyl, N, N jetylcarbamoyl, etc.) or a halogen atom eg, fluorine, chlorine, bromine, iodine.
- R 7 , R 8 , R 1Q or R 11 is represented as “norogenated, or may be, C alkyl”.
- halogen atoms eg, fluorine, chlorine, bromine, or iodine
- C alkyl eg, methinole, ethyl
- Propyl isopropyl
- Specific examples include methinole, chloromethinole, difluoromethyl, trichloromethylenole, trifluoroleomethyl, ethyl, 2-bromoethyl, 2, 2, 2_trifluoroethyl, pentafluoroethyl, propinole, 3, 3, 3_trifluoropropyl.
- these salts include, for example, inorganic acids (for example, hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid, etc.) Or organic acids (for example, acetic acid, trifluoroacetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citrate, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, etc. ) And the like are used.
- inorganic acids for example, hydrochloric acid, phosphoric acid, hydrobromic acid, sulfuric acid, etc.
- organic acids for example, acetic acid, trifluoroacetic acid, formic acid, propionic acid, fumaric acid, maleic acid, succinic acid, tartaric acid, citrate, malic acid, oxalic acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, etc.
- an inorganic base for example, an alkali metal or an alkaline earth metal such as sodium, potassium, calcium, magnesium
- organic base for example, triethylamine
- R 9 represents a halogenated C alkyl (eg, trichloromethyl, trif
- Alkoxysulfinyl eg, methoxysulfinyl, ethoxys
- N, N-di C alkylaminosulfonyl eg, N, N-dimethylamino
- Shea C alkyl-carbonyl eg, acetyl, propionyl, etc.
- C alkoxycarbonyl eg, methoxycarbonyl, ethoxycarbonyl, etc.
- N, N Di-C alkyl rubamoyl eg, N, N-dimethylcarbamoyl, N, N-jet
- Tilcarbamoyl etc. or a halogen atom (eg, fluorine, chlorine, bromine, iodine).
- a halogen atom eg, fluorine, chlorine, bromine, iodine
- the benzenediazonium salt represented by the formula (I) is produced according to a method known per se, for example, the method described in New Experimental Chemistry Course 14, P.1564-P. 1573, or the like.
- the power to do S for example, the expression ():
- a ring has the same meaning as in formula (I)
- the produced benzene diazo salt may be isolated from the reaction solution and used for the diazo coupling reaction in the next step, or may be polar so as to have a predetermined ratio in the reaction solution without isolation.
- An organic solvent and a 2,3-dihydrobenzofuran derivative may be added and subjected to a diazo coupling reaction in situ.
- the azo coupling reaction between the benzenediazonium salt represented by the formula (I) and the 2,3-dihydrobenzofuran derivative represented by the formula (II) By proceeding in a mixed solvent consisting essentially of the solvent, the process proceeds with good yield.
- the organic solvent may be any solvent as long as it does not inhibit the reaction.
- nitriles eg, acetonitrile, propionitrile, etc.
- esters eg, methyl acetate, ethyl acetate, ethyl propionate, etc.
- ketones Eg, acetone, 2-butanone, etc.
- alcohols eg, methanol, ethanol, propanol, methoxyethanol, etc.
- ethers eg, ethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.
- organic solvents may be used alone or in combination of two or more.
- substantially means that the reaction is impractical in addition to a mixed solvent containing no other solvent (that is, a solvent other than water and an organic solvent (excluding carboxylic acid solvents)). It includes a mixed solvent containing other solvents in an amount ratio that does not inhibit to any extent.
- the carboxylic acid solvent means a solvent having a carboxyl group.
- the “amount ratio that does not inhibit the reaction to an impractical level” may vary depending on the type of other organic solvent, but usually 70% (v / v) or more of the mixed solvent is preferable. It is preferably 80% (v / v) or more, more preferably 90% (v / v) or more.
- the “other solvent” that can be used is not particularly limited.
- carboxylic acids eg, carboxylic solvents such as formic acid, acetic acid, propionic acid, butyric acid
- amides eg, dimethylformamide, dimethylacetamide.
- N-methylpyrrolidone hexamethylphosphoramide and the like
- dimethylsulfoxy and the like e.g., dimethylsulfoxy and the like.
- acetonitrile, acetone and methyl acetate are preferable as the organic solvent.
- the mixing ratio of water and organic solvent is 1:99 to 99: 1, preferably 10:90 to 90:10 by volume.
- the azo coupling reaction may be carried out by reacting 1 mol of the 2,3-dihydrobenzofuran derivative represented by the formula (II) with the benzenediazonium salt represented by the formula (I). Perform in mole ratio.
- the reaction temperature is 20 to 200 ° C, preferably 0 to 150 ° C, and the reaction time is 0.5 to 100 hours.
- the obtained compound of the formula (III) can be easily isolated by a conventional method such as extraction or crystallization, if necessary.
- Reduction can be achieved by using sodium nitrite or palladium or Raney as the reducing agent.
- a catalytic reduction method using Nikel or the like as a catalyst is used.
- sodium nitrite is preferred.
- the sodium nitrite used for formula (III) is 0.5-20 equivalents and the reaction temperature is 20 forces 200 ° C, preferably 0-150 ° C. It is.
- This reduction reaction proceeds in a good yield by performing it in a mixed solvent of water and an organic solvent.
- the organic solvent any solvent may be used as long as it does not inhibit the reaction.
- nitriles eg, acetonitrile, propionitryl
- esters eg, methyl acetate, ethyl acetate, ethyl propionate
- Ketones eg, acetone, 2-butanone, etc.
- carboxylic acids eg, formic acid, acetic acid, propionic acid, butyric acid, etc.
- alcohols eg, methanol, ethanol, propanol, methoxyethanol, etc.
- ethers examples, ethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.
- amides eg, dimethylformamide, dimethylacetamide, N_methylpyrrolidone, hexamethylphosphamide, etc.
- dimethyl sulfoxide etc.
- the reaction temperature is ⁇ 20 to 200 ° C., preferably 0 to 150 ° C.
- the reduction reaction may be any solvent as long as the reaction is not inhibited.
- nitriles eg, acetonitrile, propionitryl
- esters eg, methyl acetate, ethyl acetate, ethyl propionate
- ketones Eg, acetone, 2-butanone, etc.
- carboxylic acids eg, formic acid, acetic acid, propionic acid, butyric acid, etc.
- alcohols eg, methanol, ethanol, propanol, methoxyethanol, etc.
- ethers Examples, ethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, etc.
- amides eg, dimethylformamide, dimethylacetamide, N-methylpyrroli
- Compound (V) can be produced by reacting compound (IV) with compound (VI), optionally in the presence of a base.
- Examples of the “leaving group” represented by L 1 and L 2 in the compound (VI) include hydroxy, halogen atom (eg, fluorine, chlorine, bromine, iodine, etc.), halogenated C
- alkylsulfonyloxy eg, methanesulfonyloxy, ethanesulfonyloxy, trichloromethanesulfonyloxy, etc.
- optionally substituted c-arylsulfone Nyloxy etc. are mentioned. “Optionally substituted C arylsulfonyl
- xy examples include C-anolequinole (eg, methinole, ethyl, propyl, isopropylinole,
- the amount of compound (VI) to be used is about 1.0 to about 5.0 monole, preferably about 1.0 to about 2.0 monole per 1 mol of compound (IV).
- base examples include basic salts such as sodium carbonate, potassium carbonate, cesium carbonate and sodium hydrogen carbonate, aromatic amines such as pyridine and lutidine, triethylamine, tripropinoleamine, tributylamine, Tertiary amines such as cyclohexyldimethylamine, 4-dimethylaminoviridine, N, N-dimethylaniline, N-methylbiperidine, N-methylpyrrolidine, N-methylmorpholine, sodium hydride, potassium hydride, etc.
- alkali metal hydrides examples include alkali metal hydrides, metal amides such as sodium amide, lithium diisopropylamide, lithium hexamethyldisilazide, and metal alkoxides such as sodium methoxide, sodium ethoxide, and strong tert-butoxide. It is done.
- the amount of the base to be used is about 1.0 to about 10.0 mol, preferably about 2.0 to about 5.0 mol, per 1 mol of compound (IV). If desired, it can also be produced by reacting in the presence of a quaternary ammonium salt together with a base.
- quaternary ammonium salt examples include tetraptylammonium salt and the like.
- the quaternary ammonium salt is used in an amount of about 0.1 to about 2.0 moles, preferably f-thread thread thread 1.0 monole, per mole of compound (IV).
- This reaction is advantageously performed using a solvent inert to the reaction.
- a solvent is not particularly limited as long as the reaction proceeds.
- a solvent is not particularly limited as long as the reaction proceeds.
- a solvent such as a solvent or a mixed solvent thereof is preferable.
- the reaction time is usually about 30 minutes and about 48 hours, preferably about 1 hour and about 24 hours.
- the reaction temperature is usually about ⁇ 20 to about 200 ° C., preferably about 0 to about 150 ° C.
- optically active compound (IV) can be optically resolved by a known method. Specifically, for example, the compound (IV) or a salt thereof is induced to form a salt with an optically active acidic compound and optically resolved as follows, whereby the optically active form of compound (IV) or a salt thereof is obtained.
- Manufacture power S is possible.
- a diastereomeric salt is formed by reacting compound (IV) with an optically active acidic compound as an acidic resolving agent in a suitable solvent.
- the optically active acidic compound include an optically active tartaric acid derivative such as an optically active ⁇ , ⁇ '-sianole tartaric acid derivative, an optically active amino acid derivative such as an optically active N-asinole amino acid, a formula:
- Ar represents an optionally substituted aromatic hydrocarbon group
- R a and R b represent a hydrogen atom, an optionally substituted lower alkyl group, a substituent, respectively.
- a lower alkoxy group which may have a substituent, a force indicating a halogen atom or a nitro group, or R b together with a substituent, an alkylene group or a substituent. It has a label, but it shows a real range. * Indicates the position of the asymmetric carbon.
- Optically active phosphorus represented by And acid derivatives.
- the preferred acyl group of the diacil tartaric acid derivative is, for example, a lower (C) alkanoyl group such as acetylenole, propionyl, butyryl, valeryl, benzoyl, ⁇ -
- Aroyl groups such as chlorobenzoyl and naphthoyl. ⁇ ⁇ ⁇ '_ Di-acyl tartaric acid
- the most preferred one is ⁇ , ⁇ '-di- ( ⁇ -toluoyl) tartaric acid.
- ⁇ ⁇ acyl group of the ⁇ ⁇ acylamino acid derivative include lower (C) alkanoyl groups such as acetyl, propionyl, butyryl, and valeryl, benzoyl, ⁇ -chloro
- Examples include aroyl groups such as rubenzoyl and naphthoyl.
- Examples of amino acids include
- phenyldaricin Most preferred as a sacylamino acid derivative is __ (3,5-dinitrobenzoyl) 1-a-phenylglycine.
- the optically active phosphoric acid derivative can be easily obtained according to the method described in JP-A 61-103886, J. Org. Chem., 50, 4508 (1985), etc.
- This compound can also be easily obtained as a commercial product.
- the obtained compound (V) has low toxicity, for example, neurotrophic factor-like action, neurotrophic factor activity enhancing action, neurodegeneration inhibitory action, ⁇ -amyloid toxicity inhibitory action, neurogenesis and regeneration promoting action, neural stem cell and It has excellent pharmaceutical actions such as proliferation and differentiation promoting action in sputum or nerve cells, and is useful as a medicine for mammals including humans.
- Compounds (III) and (Ilia) are useful as intermediates for the synthesis of compound (V).
- compound (V) is, for example, a neurodegenerative disease (eg, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, spinocerebellar degeneration), mental Neurological disorders (eg, schizophrenia), head trauma, spinal cord injury, cerebrovascular disorder, cerebrovascular It is effective against dementia, peripheral neuropathy (eg, diabetic neuropathy, etc.), etc., and is used as a prophylactic / therapeutic agent for these diseases.
- Compound (V) is also used for circulatory diseases such as stroke.
- Examples of the compound (V) include (5) -dimethoxy-2_ [2,2,4,6,7_pentamethinole 3 _ (4_methinorefinole) 1, 2, _Dihydro 1-Benzofuran 5-Inole] isoindoline, 5,6-Dimethoxy _ 2_ [3- (4-Isopropylphenol) 1, 2, 2, 4, 6, 7 Pentamethyl 1 2 , 3 Dihydro-1 1-benzofuran-5 Inole] isoindoline, not included in Compound V) (R) _ 5, 6-Dimethoxy 1 2_ [2, 2, 4, 6,, 7 Pentamethyl 1 3- (4 Methylphenol 1) 2,3 Dihydro-1 1-Benzofuran 1_Inole] isoindoline or (R) _ 5,6-Dimethoxy _ 2_ [2, 2, 4, 6, 7_Pentamethylol 3- (4-methylphenol) 2) 1 2, 3 Dihydro 1-benzofuran 1-5] isoindoline hydroch
- Compound (V) can be used as a prophylactic / therapeutic agent for the above diseases in a pharmaceutical composition or preparation according to known methods, for example, the methods described in EP483772A, WO00 / 34262 and WO 03/051355. .
- the wet crystals were added to a mixed solution of toluene and 2N aqueous sodium hydroxide solution, and after separation, the organic layer was concentrated.
- the concentrate was recrystallized from aqueous methanol, and the obtained crystals were dried under reduced pressure to give the title compound (3.5 g, yield 86%).
- the wet crystals were added to a mixed solution of toluene (20 mL) and 2N aqueous sodium hydroxide (20 mL), dissolved by heating at 60 ° C. After liquid separation, the organic layer was concentrated. The concentrate was dissolved in methanol (10 mL) with heating, and water (10 mL) was added. The mixture was stirred at 65 to 70 ° C for 1 hour, then allowed to cool to room temperature, and further stirred at 0 to 5 ° C for 1 hour. The precipitated crystals were collected by filtration, and the crystals were washed with a mixed solution of methanol (5 mL) and water (5 mL). The crystals were dried under reduced pressure to give the title compound (2.4 g, yield 87%).
- an aromatic azo compound having a diazo group at the 5-position of the 2,3-dihydrobenzofuran ring, and having an amino group or an isoindolyl group at the 5-position from the raw material can be provided.
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006531962A JPWO2006022311A1 (ja) | 2004-08-27 | 2005-08-25 | アゾ化合物とその製造方法 |
US11/661,183 US7521545B2 (en) | 2004-08-27 | 2005-08-25 | Azo compounds and process for production thereof |
CA002576063A CA2576063A1 (en) | 2004-08-27 | 2005-08-25 | Azo compounds and process for production thereof |
EP05774858A EP1783121A4 (en) | 2004-08-27 | 2005-08-25 | AZOVER BINDINGS AND METHOD FOR THE PRODUCTION THEREOF |
IL180999A IL180999A (en) | 2004-08-27 | 2007-01-28 | Azo compounds and process for production thereof |
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JP2004248217 | 2004-08-27 | ||
JP2004-248217 | 2004-08-27 |
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PCT/JP2005/015390 WO2006022311A1 (ja) | 2004-08-27 | 2005-08-25 | アゾ化合物とその製造方法 |
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US (1) | US7521545B2 (ja) |
EP (1) | EP1783121A4 (ja) |
JP (1) | JPWO2006022311A1 (ja) |
KR (1) | KR20070046136A (ja) |
CN (1) | CN101010311A (ja) |
CA (1) | CA2576063A1 (ja) |
IL (1) | IL180999A (ja) |
WO (1) | WO2006022311A1 (ja) |
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JP7079216B2 (ja) * | 2018-03-13 | 2022-06-01 | Jnc株式会社 | アゾベンゼン誘導体及びその製造方法 |
CN114456084B (zh) * | 2022-02-09 | 2023-06-30 | 中国科学院化学研究所 | 一种芳香偶氮化合物的合成方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH10330380A (ja) * | 1996-08-29 | 1998-12-15 | Takeda Chem Ind Ltd | 縮合環状エーテル類、その製造法および剤 |
JP2002265460A (ja) * | 2000-12-28 | 2002-09-18 | Takeda Chem Ind Ltd | 光学活性2,3−ジヒドロベンゾフラン化合物の製造法 |
JP2003104981A (ja) * | 2001-07-13 | 2003-04-09 | Takeda Chem Ind Ltd | ベンゾフラン誘導体の製造法 |
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US2397212A (en) * | 1939-07-14 | 1946-03-26 | Regents | Process of producing tocopherollike compounds |
WO1998008842A1 (en) | 1996-08-29 | 1998-03-05 | Takeda Chemical Industries, Ltd. | Cyclic ether compounds as sodium channel modulators |
CN1297550C (zh) * | 1998-12-04 | 2007-01-31 | 武田药品工业株式会社 | 苯并呋喃衍生物及其制备和用途 |
ES2317935T3 (es) * | 2000-10-05 | 2009-05-01 | Takeda Pharmaceutical Company Limited | Promotores de la proliferacion y diferenciacion de celulas pluripotenciales y/o celulas precursoras neuronales. |
CA2432410A1 (en) | 2000-12-28 | 2002-07-11 | Takeda Chemical Industries, Ltd. | Process for preparing optically active 2,3-dihydro- benzofuran compounds |
ATE406357T1 (de) | 2001-07-13 | 2008-09-15 | Takeda Pharmaceutical | Verfahren zur herstellung von benzofuranderivaten |
-
2005
- 2005-08-25 EP EP05774858A patent/EP1783121A4/en not_active Withdrawn
- 2005-08-25 CN CNA2005800289557A patent/CN101010311A/zh active Pending
- 2005-08-25 CA CA002576063A patent/CA2576063A1/en not_active Abandoned
- 2005-08-25 JP JP2006531962A patent/JPWO2006022311A1/ja active Pending
- 2005-08-25 US US11/661,183 patent/US7521545B2/en not_active Expired - Fee Related
- 2005-08-25 WO PCT/JP2005/015390 patent/WO2006022311A1/ja active Application Filing
- 2005-08-25 KR KR1020077004298A patent/KR20070046136A/ko not_active Application Discontinuation
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH10330380A (ja) * | 1996-08-29 | 1998-12-15 | Takeda Chem Ind Ltd | 縮合環状エーテル類、その製造法および剤 |
JP2002265460A (ja) * | 2000-12-28 | 2002-09-18 | Takeda Chem Ind Ltd | 光学活性2,3−ジヒドロベンゾフラン化合物の製造法 |
JP2003104981A (ja) * | 2001-07-13 | 2003-04-09 | Takeda Chem Ind Ltd | ベンゾフラン誘導体の製造法 |
Non-Patent Citations (1)
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See also references of EP1783121A4 * |
Also Published As
Publication number | Publication date |
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US7521545B2 (en) | 2009-04-21 |
US20080009539A1 (en) | 2008-01-10 |
CA2576063A1 (en) | 2006-03-02 |
EP1783121A1 (en) | 2007-05-09 |
KR20070046136A (ko) | 2007-05-02 |
JPWO2006022311A1 (ja) | 2008-05-08 |
IL180999A (en) | 2010-11-30 |
CN101010311A (zh) | 2007-08-01 |
IL180999A0 (en) | 2007-07-04 |
EP1783121A4 (en) | 2009-08-05 |
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