WO1994013675A1 - Nouveau procede de production pour un derive de pyrazolotriazole - Google Patents

Nouveau procede de production pour un derive de pyrazolotriazole Download PDF

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Publication number
WO1994013675A1
WO1994013675A1 PCT/JP1993/001803 JP9301803W WO9413675A1 WO 1994013675 A1 WO1994013675 A1 WO 1994013675A1 JP 9301803 W JP9301803 W JP 9301803W WO 9413675 A1 WO9413675 A1 WO 9413675A1
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WO
WIPO (PCT)
Prior art keywords
atom
lower alkyl
alkyl group
compound
general formula
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.)
Ceased
Application number
PCT/JP1993/001803
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English (en)
Japanese (ja)
Inventor
Toshio Okazaki
Toshihiro Watanabe
Isao Yanagisawa
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.)
Yamanouchi Pharmaceutical Co Ltd
Original Assignee
Yamanouchi Pharmaceutical Co Ltd
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 Yamanouchi Pharmaceutical Co Ltd filed Critical Yamanouchi Pharmaceutical Co Ltd
Priority to AU56593/94A priority Critical patent/AU5659394A/en
Publication of WO1994013675A1 publication Critical patent/WO1994013675A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention relates to a novel method for producing a pyrazo-mouth triazole derivative having an angiotensin II (hereinafter abbreviated as All) antagonism, and a novel compound used in the method.
  • All angiotensin II
  • Angiotensin converting enzyme acts on and converts it to All.
  • the virazolotriazole derivative or a salt thereof provided by the present invention acts on the All receptor and suppresses the expression of All, and is therefore useful as a medicine, especially as an All antagonist.
  • the present inventors previously produced the pyrazolotriazole compound (VII) for the first time by the method represented by the following reaction formula, and filed a patent application for this compound (International Publication No. WO 93/05044). )
  • R represents a hydrogen atom or a lower alkyl group
  • R 5 represents an aralkyl group
  • X 3 represents a halogen atom or a sulfonic acid residue.
  • the method involved the production of the desired compound from a pyrazolotriazole compound (I) and a biphenylmethyl halide (or sulfonate). Disclosure of the invention
  • the production method of the present invention is characterized in that an object is produced by a different route from the above production method.
  • the present invention relates to the general formula
  • R is the same or different and represents a hydrogen atom or a lower alkyl group.
  • X 1 and X 2 are the same or different and each represents a halogen atom).
  • R 1 is the same or different and is a lower alkyl group, or both are a lower alkylene group
  • R 2 is a lower alkyl group
  • R 3 is a hydrogen atom or a lithium atom.
  • M is zinc atom, magnesium atom. Copper atom, boron atom, aluminum atom or cadmium atom, ligand X is halogen atom, n is valence of metal M, R 4 Represents a hydrogen atom or a lower alkyl group, and is reacted with a compound (IV) represented by the formula:
  • a novel production method characterized by comprising a third step of obtaining a pyrazolo triazole derivative of the compound (VII) or a salt thereof represented by the following formula:
  • Compounds (II), (IV) and (V) in the above-mentioned production method of the present invention are novel, and the production method of the present invention is characterized in that these novel intermediates are used.
  • the present application also includes the following inventions relating to these novel compounds and their production methods.
  • the lower alkyl group represented by R 1 , R 1 , R 2 or R 4 means a straight or branched carbon chain having 1 to 6 carbon atoms, specifically, a methyl group, an ethyl group, a propyl group.
  • R 1 Two of these R 1 may be combined with each other to form a lower alkylene group.
  • the lower alkylene group formed in this case means a linear or branched carbon chain having 2 to 7 carbon atoms, specifically, an ethylene group, a trimethylene group, a tetramethylene group.
  • Examples of one MXn—i in R 3 include —ZnC1, one MgC1, one CuC1, one BC12, one CdCl, —ZnBr, one MgBr group, one C u B r group, - BB r 2 group, Mataichi B (OR 4) 2 as for example mono- B (OH) 2 group, may be mentioned an B (OCH 3) 2 and the like.
  • the halogen atom in X, X 1 or X 2 means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • the first step is the N-aralkylation of pyrazolotriazole (I) with halogenophenylmethyl halide (II).
  • the product ( ⁇ ) obtained in this step is a new compound.
  • This N-aralkylation is carried out by stirring compound (I) and a corresponding amount of compound (II) in an inert solvent under ice-cooling or room temperature.
  • inert solvent examples include getyl ether, tetrahydrofuran, dioxane, dimethoxetane, hexane, benzene, dichloromethane, chloroform, .N, N-dimethylformamide, N, N-dimethylacetamide. , Water, etc. or mixtures thereof o
  • Bases include potassium t-butoxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, and sodium hydroxide.
  • Sodium hydride, sodium metal, sodium methoxide, pyridine, triethylamine, picolin, lutidine and the like are used.
  • the compound ( ⁇ ⁇ ) obtained in the first step and a corresponding amount of the compound (IV) are reacted with an inert solvent such as getyl ether, tetrahydrofuran, dioxane, hexane or benzene.
  • an inert solvent such as getyl ether, tetrahydrofuran, dioxane, hexane or benzene.
  • a phosphinated Nigel or a palladium catalyst activated with a Grignard reagent such as methylmagnesium bromide or an aluminum halide reagent, if necessary, is used as a reaction promoting substance. .
  • the compound (IV) used in this step is a novel compound and is prepared as follows.
  • R la, R 8 is the lower alkyl group, R 6, R 7 are the same or different connexion hydrogen atom, the lower alkyl group. Or R la, R 6 carbon atoms become both integral It means 3 to 6 lower alkylene groups.
  • R 1 , R, R 4 , M, X or n are as defined above.
  • compound (IV) is reacted with a corresponding amount of compound (X) or compound (XI) in an inert solvent at room temperature to under heating or heating to reflux to obtain compound (IVa). Then, the compound (IVa) is reacted with a corresponding amount of alkyllithium, preferably n-butyllithium, to obtain a lithium compound (IVb). The compound (IVb) is further reacted with a corresponding amount of metal halide. To give compound (IVc), Alternatively, compound (IVd) is obtained by reacting compound (IVb) with a tri-lower alkyl borate in an amount corresponding to the reaction.
  • the elimination reaction can be carried out by acid hydrolysis or acid solvolysis of compound (V).
  • compound (V) and an acid such as acetic acid, trifluoroacetic acid, trichloroacetic acid, hydrochloric acid, sulfuric acid, hydrobromic acid monoacid, etc. are dissolved in methanol,
  • the treatment is carried out in an organic solvent such as ethanol or acetone in the presence or absence of water or in water at room temperature or under heating (or under reflux).
  • the present invention provides a new method for producing an industrially useful pyrazolotriazole derivative (VII).
  • the final compound (VI I) obtained by the production method of the present invention has angiotensin II (All) antagonistic action, it can be used for various diseases (hypertension, chronic heart failure, diabetes) caused by the physiological action of All. It is useful for the treatment of early nephropathy in genital nephropathy (urine microalbumin) and suppression of urinary protein in chronic glomerulonephritis.

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

Abstract

On décrit un nouveau procédé de production concernant un dérivé de pyrazolotriazole représenté par la formule générale suivante, aisi qu'un composé utile pour ce procédé: oú les R peuvent être identiques ou différents et représenter chacun hydrogène ou alkyle inférieur.
PCT/JP1993/001803 1992-12-14 1993-12-13 Nouveau procede de production pour un derive de pyrazolotriazole Ceased WO1994013675A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU56593/94A AU5659394A (en) 1992-12-14 1993-12-13 Novel process for producing pyrazolotriazole derivative

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP35365792 1992-12-14
JP4/353657 1992-12-14

Publications (1)

Publication Number Publication Date
WO1994013675A1 true WO1994013675A1 (fr) 1994-06-23

Family

ID=18432336

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1993/001803 Ceased WO1994013675A1 (fr) 1992-12-14 1993-12-13 Nouveau procede de production pour un derive de pyrazolotriazole

Country Status (2)

Country Link
AU (1) AU5659394A (fr)
WO (1) WO1994013675A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007504272A (ja) * 2003-05-16 2007-03-01 イシス イノベイション リミテッド 有機燐光材料および有機オプトエレクトロニクス素子

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4898029A (fr) * 1972-02-28 1973-12-13
JPS60130572A (ja) * 1983-12-15 1985-07-12 Sumitomo Chem Co Ltd ５−（ｐ−ニトロフエニル）テトラゾ−ル誘導体
JPS60172982A (ja) * 1984-02-16 1985-09-06 Fuji Photo Film Co Ltd ピラゾロ〔１，５−ｂ〕〔１，２，４〕トリアゾ−ル誘導体
JPS6291948A (ja) * 1985-10-18 1987-04-27 Fuji Photo Film Co Ltd ハロゲン化銀カラ−写真感光材料

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS4898029A (fr) * 1972-02-28 1973-12-13
JPS60130572A (ja) * 1983-12-15 1985-07-12 Sumitomo Chem Co Ltd ５−（ｐ−ニトロフエニル）テトラゾ−ル誘導体
JPS60172982A (ja) * 1984-02-16 1985-09-06 Fuji Photo Film Co Ltd ピラゾロ〔１，５−ｂ〕〔１，２，４〕トリアゾ−ル誘導体
JPS6291948A (ja) * 1985-10-18 1987-04-27 Fuji Photo Film Co Ltd ハロゲン化銀カラ−写真感光材料

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2007504272A (ja) * 2003-05-16 2007-03-01 イシス イノベイション リミテッド 有機燐光材料および有機オプトエレクトロニクス素子

Also Published As

Publication number Publication date
AU5659394A (en) 1994-07-04

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