WO2002055482A1 - Procede de preparation d'amides d'acide carboxylique - Google Patents

Procede de preparation d'amides d'acide carboxylique Download PDF

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Publication number
WO2002055482A1
WO2002055482A1 PCT/JP2001/011580 JP0111580W WO02055482A1 WO 2002055482 A1 WO2002055482 A1 WO 2002055482A1 JP 0111580 W JP0111580 W JP 0111580W WO 02055482 A1 WO02055482 A1 WO 02055482A1
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WO
WIPO (PCT)
Prior art keywords
carboxylic acid
group
compound
producing
acid
Prior art date
Application number
PCT/JP2001/011580
Other languages
English (en)
Japanese (ja)
Inventor
Jo Ooyama
Hideo Tanabe
Susumu Harashima
Original Assignee
Sankyo Company,Limited
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 Sankyo Company,Limited filed Critical Sankyo Company,Limited
Publication of WO2002055482A1 publication Critical patent/WO2002055482A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines

Definitions

  • the present invention relates to a method for producing a carboxylic acid amide compound. [Background technology]
  • a method for producing a carboxylic acid amide compound by reacting a carboxylic acid compound and an amino compound a method using a condensing agent or a method for converting a carboxylic acid into an activated form (for example, an acid halide compound or an acid anhydride) After that, a method of reacting with an amino compound is known.
  • a method using an alkanephosphonic anhydride is known (US Pat. No. 5,055,591).
  • a base is used, and as the base, aliphatic and cycloaliphatic tertiary amines, specifically, methylmonorephorin, N-ethylmorpholine, and triethylamine are described.
  • the present inventors have found that by using N-alkylimidazole as a base, a reaction of condensing a carboxylic acid compound and an amino compound in the presence of an alkanephosphonic anhydride can be efficiently performed. Was completed.
  • the production method of the present invention has a general formula
  • R 1 represents a C—C 6 alkyl group.
  • R 2 represents a C 6 alkyl group
  • the "C 6 alkyl group of R 1 and R 2 " is, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a s-butyl group, a t-butyl group, a pentyl group, an isopentyl Group, 2-methylbutyl group, neopentyl group, 1-ethylpropyl group, hexyl group, isohexyl group, 4-methylpentyl group, 3-methylpentynole group, 2-methylpentyl group, 1-methylpentyl group, 3, 3- It may be a dimethylbutyl group, a 2,2-dimethylbutyl group, a 1,1-dimethylbutyl group, a 1,2-dimethylbutyl group, a 1,3-dimethylbutyl group, a 2, '3-dimethylbutyl group,
  • R 1 is preferably, C 3 - a C 6 alkyl group, more preferably a propyl or heptyl group
  • R 2 is preferably one C 4 Al A group, more preferably a methyl group or Echiru group.
  • the carboxylic acid compound is a compound having a carboxyl group and may have another functional group. However, it is desirable that the functional group be protected with an appropriate protecting group.
  • Carboxylic acid compounds include, for example, formic acid, acetic acid, propionic acid, butyric acid, N-t-butoxycarbonyl glycine, N-t-butoxycarbonylalaen, N-benzyloxyl-ponylalanine, N-t-butoxy T-toxin such as carbonylserine, N-t-butoxycanolepo-norestin, N-t-butoxycanoleponinolevalin, N-t-butoxycarbonyl renoleucine, and N-t-butoxycarboninoleisleucine It may be substituted with an amino group protected by cicarpole or benzyloxyboel.
  • protected with t-butoxycarbonyl or benzyloxycarbonyl A C 7 aliphatic carboxylic acid which may be substituted with an amino group; benzoic acid which may be substituted with methyl, methoxy, fluorine, chlorine or amino protected with t-toxycarbonyl or benzyloxycarbonyl. Or having one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur atoms, and having an imino moiety protected by t- or benzyloxycarboel.
  • a 5- or 6-membered heterocyclic carboxylic acid more preferably, formic acid, acetic acid, propionic acid, butyric acid, N-t-ptoxcanoleponinoleglycine, N-t-peptoxyforce / leponinoleanine, N- Benzinoleoxycanololepoenolealanine, N-t-ptoxycanoleponinoreserin, N-t-putoxycarbinorestin, N-t-teptoxycarborubaline, N- t-butoxycarboonuleucine, N-t-toxycarbyl isoleucine, benzoic acid, 4-methylbenzoic acid, 4-methoxybenzoic acid, 4-fluorobenzoic acid, 4-chlorobenzoic acid, 2-t-butoxycarbo-laminobenzoic acid, N-t-butoxycarbolproline, N-benzyloxy Carbonylproline, N-t-butoxycarbol-piperidine-12
  • the above amino compound is a compound having an amino group and may have another functional group, but it is preferable that the functional group is protected with an appropriate protecting group.
  • the amino compounds include, for example, methinoleamine, dimethylamine, ethylamine, propylamine, ptinoleamine, hexinoleamine, O-methinoleglycine, O-methinolealanine, O-ethinolealanine, O-t-ptinolealanine, O-benzylalanine, O-t-no-le-a-yun, otino-erin, and otino-lein.
  • I C 6 alkylamine methyl, methoxy, fluorine, chlorine, methoxycarbol, ethoxycarbol or phenylamine which may be substituted by t-butoxycarbonyl; oxygen and sulfur May have 1 or 2 heteroatoms selected from the group consisting of methoxycarbonyl, ethoxycarbol, tert-carboxycarbonyl or benzyloxycarbonyl.
  • carboxylic acid compound is of the formula
  • the most preferred amino compound is represented by the formula
  • the reaction of the production method of the present invention is carried out by reacting a carboxylic acid compound with an amino compound in an inert solvent in the presence of compound (I) and compound (II).
  • the solvent used does not inhibit the reaction.
  • aliphatic hydrocarbons such as hexane, heptane, lignin, and petroleum ether
  • aromatic hydrocarbons such as benzene, toluene, and xylene
  • methylene chloride Halogenated hydrocarbons such as chlorophonolem, carbon tetrachloride, dichloroethane, chlorobenzene, and dichlorobenzene
  • esters such as ethyl formate, ethyl acetate, propyl acetate, butyl acetate, and getyl carbonate; Sopropyl ether, tetrahydrofuran, dioxane, dimethyloxetane, diethyl Ethers such as le
  • the molar ratio of the amino compound to the carboxylic acid compound is usually 1 to 10, preferably 2 to 10, and the molar ratio of the compound (I) to the carboxylic acid compound is usually 2 to 10. To 10 and preferably 3 to 6, and the molar ratio of the compound (II) to the carbone oxide compound is usually 2 to 15 and preferably 3 to 6.
  • the amount of the solvent to be used per 1 mol of the carboxylic acid compound is usually from 500 to 200 mL, and preferably from 800 to 120 OmL.
  • the reaction temperature varies depending on the type of the carboxylic acid compound, the amino compound, the compound (1), the compound (11) or the solvent, but is usually from ⁇ 20 to 40 ° C., preferably from 0 to 40 ° C. 15 ° C.
  • the reaction time varies depending on the reaction temperature or the type of the carboxylic acid compound, amino compound, compound (1), compound (II) or solvent, but is usually 1 to 5 hours, and preferably 15 minutes. 3 hours.
  • the desired carboxylic acid amide compound is collected according to a conventional method. For example, add water to the reaction mixture, extract with an organic solvent immiscible with water, wash the extract with saturated aqueous sodium bicarbonate, saturated saline and water, dry over anhydrous magnesium sulfate, and evaporate the solvent. Thereby, the desired carboxylic acid amide compound can be obtained. Further, if necessary, the desired carboxylic acid amide compound can be obtained by recrystallization, reprecipitation, and purification using various types of chromatography.
  • the method for producing the carboxylic acid amide compound of the present invention comprises: A carboxylic acid amide compound obtained by reacting a carboxylic acid compound with an amino compound in the presence of an alkanephosphonic anhydride using imidazole, whereby the desired carboxylic acid amide compound can be efficiently produced.
  • a carboxylic acid amide compound obtained by reacting a carboxylic acid compound with an amino compound in the presence of an alkanephosphonic anhydride using imidazole, whereby the desired carboxylic acid amide compound can be efficiently produced.
  • Is useful as a pharmaceutical intermediate or a pharmaceutical US Pat. No. 5,055,591 and Japanese Patent Application Laid-Open No. 5-213913).
  • Ethyl acetate (8 OmL) and aqueous sodium hydrogen carbonate (6 OmL) were added to the reaction solution, the layers were separated, and the obtained organic layer was washed with water (2 ⁇ 5 OmL).
  • the obtained organic layer was evaporated under reduced pressure to 8 OmL, methanol (18 lmL) was added, and the mixture was further evaporated to 14 OmL under reduced pressure, and then decolorized with activated carbon (1.6 g).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne un procédé de préparation d'une amide d'acide carboxylique par réaction d'un acide carboxylique avec un composé amino en présence d'un anhydride alcanephosphonique et un N-alkylimidazole. Ce procédé permet de préparer de manière efficace des amides d'acide carboxylique qui sont des médicaments ou intermédiaires de médicaments utiles.
PCT/JP2001/011580 2001-01-05 2001-12-27 Procede de preparation d'amides d'acide carboxylique WO2002055482A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001-334 2001-01-05
JP2001000334 2001-01-05

Publications (1)

Publication Number Publication Date
WO2002055482A1 true WO2002055482A1 (fr) 2002-07-18

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Application Number Title Priority Date Filing Date
PCT/JP2001/011580 WO2002055482A1 (fr) 2001-01-05 2001-12-27 Procede de preparation d'amides d'acide carboxylique

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WO (1) WO2002055482A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2388260A1 (fr) * 2010-05-21 2011-11-23 Archimica GmbH Procédé de fabrication pour un inhibiteur d'un facteur de coagulation sanguine

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1059994A (ja) * 1996-08-13 1998-03-03 Mitsubishi Chem Corp シアル酸誘導体の製造方法
EP1160236A2 (fr) * 2000-06-02 2001-12-05 Sumitomo Chemical Company, Limited Production d'anhydride mixte et d'un composé d'amide

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH1059994A (ja) * 1996-08-13 1998-03-03 Mitsubishi Chem Corp シアル酸誘導体の製造方法
EP1160236A2 (fr) * 2000-06-02 2001-12-05 Sumitomo Chemical Company, Limited Production d'anhydride mixte et d'un composé d'amide

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2388260A1 (fr) * 2010-05-21 2011-11-23 Archimica GmbH Procédé de fabrication pour un inhibiteur d'un facteur de coagulation sanguine

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