WO2000034267A1 - Procede de production d'un compose d'amide cyclique - Google Patents

Procede de production d'un compose d'amide cyclique Download PDF

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Publication number
WO2000034267A1
WO2000034267A1 PCT/JP1999/006765 JP9906765W WO0034267A1 WO 2000034267 A1 WO2000034267 A1 WO 2000034267A1 JP 9906765 W JP9906765 W JP 9906765W WO 0034267 A1 WO0034267 A1 WO 0034267A1
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Prior art keywords
group
substituent
formula
compound
diazabicyclo
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PCT/JP1999/006765
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English (en)
Japanese (ja)
Inventor
Hideo Hashimoto
Tadashi Fukui
Tadashi Hanaoka
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Takeda Chemical Industries, Ltd.
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Priority to AU15126/00A priority Critical patent/AU1512600A/en
Publication of WO2000034267A1 publication Critical patent/WO2000034267A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Definitions

  • the present invention relates to an industrially useful method for producing active ingredients of pharmaceuticals, agricultural chemicals, and the like, or synthetic intermediates thereof.
  • European Patent Application Publication No. 567 982 (corresponding to Japanese Patent Application Laid-Open No. 6-293740) has the formula:
  • a ri represents a substituted phenyl group
  • R 2 may be the same or different and represent a hydrogen atom or a lower alkyl group, or may be linked to form a lower alkylene group
  • 3 represents a group bonded via a carbon atom
  • R 4 represents a hydrogen atom or a sacyl group, represents a nitrogen atom or a methine group, and and are the same or different and are substituted by a nitrogen atom or a lower alkyl group.
  • the azole compound represented by the formula or a salt thereof is also described in the above publication and JP-A-8-106676,
  • a 1 " 2 represents a halogenated phenyl group
  • R 5 represents an aliphatic or aromatic hydrocarbon group which may have a substituent, or an aromatic bicyclic group which may have a substituent.
  • (R) represents a configuration.
  • a preferable group of the imidazolone derivatives (Hereinafter sometimes referred to as compound (B)), and a synthesis method using (R) -lactic acid derivative as a starting material is described as a method for producing the compound.
  • European Patent Application Publication No. 687672 (corresponding to the publication of Japanese Patent Application Laid-Open No. 8-253452) describes a synthesis method using (S) -lactic acid derivative as a starting material as a method for producing compound (B). Have been.
  • JP-A-8-104676 discloses the formula:
  • a preferable group of compounds [hereinafter may be referred to as compound (C)]. ], And describes a synthesis method for subjecting the above compound (B) to a reduction reaction.
  • WO 9625410 A Japanese Unexamined Patent Application Publication No. Hei 9-183769 has a formula:
  • Ar 3 represents an optionally substituted phenyl group
  • R 6 and R 7 are the same or different and are each a hydrogen atom or a lower alkyl group, or R 6 and R 7 are combined to form a lower group.
  • An alkylene group R s is a hydrogen atom or an acyl group
  • X 2 is a nitrogen atom or a methine group
  • An azole compound having antifungal activity represented by the formula or a salt thereof is disclosed: OH CH,
  • the present invention relates to a compound of the formula useful as an objective compound or an important synthetic intermediate thereof:
  • R 1 represents a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent
  • X represents a divalent group which may have a substituent
  • Y represents a methylene group which may have a substituent
  • compound (II) having a nitrogen-alkyl bond in the molecule thereof. It is something to try.
  • the present invention is a.
  • the basic amines are trimethylamine, triethylamine, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane,
  • R 2 and R 3 each represent a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent, or R 2 and R 3 are (1)
  • X is a divalent group in which 1 to 4 atoms selected from a carbon atom, a nitrogen atom, an oxygen atom, a sulfur atom and a silicon atom are connected in series and may have a substituent.
  • R 4 represents a hydrogen atom, a hydrocarbon group which may have a substituent, or a heterocyclic group which may have a substituent, and other symbols are as defined above.
  • R 1 represents a hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent
  • X represents a divalent group which may have a substituent
  • Y represents a methylene group which may have a substituent
  • Z represents an acyloxy group.
  • the “hydrocarbon group” in the “optionally substituted hydrocarbon group” represented by R 1 examples include an aliphatic hydrocarbon group, an aromatic hydrocarbon group, and an araliphatic hydrocarbon group.
  • the aliphatic hydrocarbon group examples include an alkyl group, a cycloalkyl group, a cycloalkylalkyl group, an alkenyl group, and an alkynyl group.
  • the alkyl group include methyl, ethyl, n-propyl, isopropyl, and n.
  • the cycloalkyl group includes, for example, cyclo Examples thereof include cycloalkyl groups having 3 to 10 carbon atoms such as propyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and adamantyl. Particularly, cycloalkyl groups having 3 to 6 carbon atoms (eg, cyclopropyl, cyclobutyl) Tyl, cyclopentyl and cyclohexyl) are preferred.
  • Examples of the cycloalkylalkyl group include those having 4 to 12 carbon atoms such as cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl. Among them, cycloalkylalkyl groups having 6 to 8 carbon atoms (eg, cyclopentylmethyl, Cyclohexylmethyl) is preferred.
  • Examples of the alkenyl group include those having 2 to 4 carbon atoms such as vinyl, probenyl, and butenyl, and alkenyl having 2 to 3 carbon atoms (eg, vinyl, probenyl) is preferable.
  • alkynyl group examples include those having 2 to 4 carbon atoms, such as ethynyl, propynyl, and butynyl. Among them, alkynyl having 2 to 3 carbon atoms (eg, ethynyl, propynyl) is preferable.
  • aromatic hydrocarbon group examples include those having 6 to 14 carbon atoms such as phenyl, naphthyl, biphenyl, anthryl, and indenyl, and particularly preferably an aryl group having 6 to 10 carbon atoms (eg, phenyl, naphthyl). .
  • Examples of the araliphatic hydrocarbon group include aralkyl groups having 7 to 15 carbon atoms, such as benzyl, phenethyl, phenylpropyl, naphthylmethyl, indanyl, indanylmethyl, 1,2,3,4-tetrahydronaphthyl, 2,3,4-tetrahydronaphthylmethyl and the like are preferable, and an aralkyl group having 7 to 11 carbon atoms (eg, benzyl, phenethyl, naphthylmethyl and the like) is particularly preferable.
  • aralkyl groups having 7 to 15 carbon atoms such as benzyl, phenethyl, phenylpropyl, naphthylmethyl, indanyl, indanylmethyl, 1,2,3,4-tetrahydronaphthyl, 2,3,4-tetrahydronaphthylmethyl and the like are preferable, and an a
  • the “heterocyclic group” of the “heterocyclic group optionally having substituent (s)” for R 1 represents a group formed by removing one hydrogen atom bonded to the heterocyclic ring.
  • the ring includes, for example, a 5- to 8-membered ring containing 1 to several, preferably 1 to 4 hetero atoms such as a nitrogen atom (which may be oxidized), an oxygen atom and a sulfur atom, or a fused ring thereof. Show.
  • heterocyclic group examples include pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, furyl, chenyl, oxazolyl, isoxazolyl, and 1,2: 3-oxadiazolyl, 1,2,4 mono-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, thiazolyl, isothiazolyl, 1,2,3_thiaziazolyl , 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, pyrrolidinyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, piberidinyl, piperazinyl, indolyl, pyranyl, thioviranyl, dioxynil, diox
  • Examples of the substituent in the “hydrocarbon group which may have a substituent” and the “heterocyclic group which may have a substituent” represented by R 1 include, for example, an aryl group (halogenated may be), a heterocyclic group, Okiso group, a hydroxyl group, Ji Bok 6 alkoxy group, Ji 3 _ 1 () cycloalkyl O alkoxy group,. Ariruokishi group, C 7 _ 19 7 Lal Kiruokishi group, a heterocyclic Okishi group, a mercapto group, 6 alkylthio group (the sulfur atom may be Okishido reduction), C 3 ⁇ .
  • a cycloalkylthio group (the sulfur atom may be oxidized); Ariruchio group (the sulfur atom may be O key Sid reduction), Ji 7 _ 19 Ararukiruchio group (the sulfur atom may be Okishido reduction), heterocyclic Chio group, a heterocyclic sulfinyl group, a heterocyclic sulfonyl group, an amino group, a mono flicking 6 alkylamino group, di C ⁇ - 6 alkylamino group, tri ⁇ - 6 alkyl ammonium Nio group.
  • Cycloalkylamino group C 6 - 10 Ariru amino group, C 7 - 19 Ararukiruamino group, a heterocyclic Amino group, cyclic amino group, a nitro group, a halogen atom, Shiano group, forces Rupokishiru group.
  • Ariru Ichiriki Ruponiru group (: I 6 Arukanoiru group, C 3 - 5 Aruke Noiru group, C 6 - 1Q Ariru Ichiriki Ruponiruokishi groups, C 2 - 6 alkanoyloxy noisy Ruo alkoxy group, C 3 - 5 alkenyl noisy Ruo alkoxy group
  • aryl group examples include phenyl, naphthyl, 2-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, and the like
  • (: 6- alkoxy group” includes, for example, methoxy, ethoxy, n-propoxy, Isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n_hexyloxy and the like include “(: 3 ⁇ .cycloalkyloxy group” such as cyclopropyloxy, Kishiruokishi etc., as "C 6 _ 1Q Ariruokishi group” for example, phenoxy, etc.
  • Nafuchiruokishi is, as "c 7 _ 19 Ararukiruokishi group” for example, Benjiruokishi, 1 phenylene Ruechiruokishi, 2-phenylalanine E chill O alkoxy, Benzhydryloxy and the like, "( ⁇ _ 6 alkylthio group (the sulfur atom is oxidized Is as also may) "have for example, methylthio, Echiruchio, .eta.
  • tri C i-e alkyl ammonium Nio group such as trimethyl ammonium Nio is, "C 3 - 1 () cyclo
  • alkylamino group examples include cyclopropylamino, Cyclopentyl Rua Mino, etc. Kishiruamino cyclohexane is: a '(6 _ 1 () Ariruamino group ", for example, Anirino, such as N- Mechiruanirino is - as the".
  • Araru Kiruamino group for example, Benjiruamino, 1 1-phenylethylamino, 2-phenylethylamino, benzhydrylamino and the like.
  • cyclic amino group include 1-pyrrolidinyl, piperidino, 1-piperazinyl, morpholino and thiomorpholino.
  • halogen atom include fluorine, chlorine, bromine and iodine
  • examples of the "J. alkoxy monocarbonyl group” include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, and isopropoxy.
  • Pol cycloalkenyl O alkoxycarbonyl is, as the "C 6 _ 1 Q ⁇ Li one Ruo Kishi carbonyl group", for example, phenoxy carbonyl, such as Nafuchiruoki aryloxycarbonyl is, "Ji 7 - 1 9 Ararukiruokishi _ Karuponiru group", as listed above, benzyl O carboxymethyl Cal Poni Le and benzhydryl Ruo alkoxycarbonyl is, "C 6 _ 1 Q ⁇ Li one Rukaruponiru group” the example, Benzoiru, naphthoyl, Fueniruasechiru etc., as "Ji 6 Arukanoiru group", for example, formyl, Asechiru, propionyl, butyryl, valeryl, Pibaroiru like: the "(3 _ 5 Arukenoiru group”, for example, Acryloyl, Crotnoyl But,
  • Aminokaruponiru group is used, specifically, for example, force Rubamoiru, N- methylcarbamoyl, N- E Ji carbamoyl, N, N- dimethyl-carba Moyl, N, N-Jetylcarbamoyl, N-phenylcarbamoyl, N-acetylcarbamoyl, N-benzoylcarbamoyl, N- (p-methoxyphenyl) potassylcarbamoyl, 1-pyrrolidinylcarbonyl, piperidinylmethyl squaring Lupo sulfonyl, -1-piperidines Rajini Luca Lupo sulfonyl, such as
  • Rubamoiruokishi group which may force Rubamoiruokishi group "even though, for example, ⁇ - 4 alkyl group (e.g., methyl, E Chi le, etc.), phenyl
  • a carbamoyloxy group optionally substituted with one or two substituents selected from groups such as carbamoyloxy, N-methylcarbamoyloxy, N, N-dimethylcarbamoyl Okishi, N over E Ji carbamoyl O carboxymethyl, etc.
  • N- Hue carbamoylmethyl O alkoxy is, as "C, _ 6 alk noisy Rua amino group", for example, Asetoamido, propionamide, Puchiroamido, Bareroamido, Pibaroamido; ⁇ etc. is , RCe.
  • aryloxyponylamino groups include rc ⁇ , such as benzamide, naphthamide, and fuimiido.
  • the alkoxy one carboxamide group ", methoxide Shikarupokisamido (CH 3 OCONH-), ethoxy Cal poke Sami de, etc.
  • tert- butoxide shea carboxamide is
  • Ariruokishi - it is a carboxamide group "for example, off Enoxycarpoxamide (C 6 H 5 OC ⁇ NH—) and the like are examples of “.aralkyloxy-l-l-poxamide group” such as benzyloxycarpoxamide (C 6 H 5 CH 2 OCONH—) and benzhydryl-loxyl-l-poxyamide
  • Examples of the “.alkoxy-carbonyloxy group” include, for example, methoxycarbonyloxy, ethoxycarbonyloxy, n-propoxycarbonyloxy, isopropoxycarbonyloxy, n-butoxycarboxyloxy, tert-butoxy.
  • Calponyloxy, n-pentylo Examples of “C 6 — i. Aryloxy one-pot carbonyl group” include xycarbonyloxy, n-hexyloxycarbonyloxy, and the like, for example, phenoxycarbonyloxy, naphthyloxycarboxy, and the like. , “C 7 — i 9 aralkyloxy group” Examples thereof include benzyloxycarbonyloxy, 11-phenylethyloxycarbonyloxy, 2-phenylethyloxycarbonyloxy, benzhydryloxycarbonylcarbonyl, and the like, and “C 3 _i.cycloalkyloxy”.
  • a ureido group which may be substituted with 1 to 3 substituents selected from a phenyl group and the like is used, for example, ureido, 1-methylureido, 3-methylureido, 3, Examples include 3-dimethylureide, 1,3-dimethylureide, and 3-phenylureide.
  • R 1 is an aromatic hydrocarbon group which may have a substituent or a heterocyclic group which may have a substituent
  • substituents include, for example, those described above.
  • Examples "Ji 4 _ 7 a cycloalkyl alkyl group”, for example, cyclopropylmethyl, Shikurobe Nchirumechiru Etc. is.:
  • pro Bae alkenyl is, as the "C 2 _ 3 alkynyl group", for example Echiniru, etc.
  • Puropini Le is, "C 6 - i Ariru Examples of the “group” include phenyl, naphthyl, and the like, “(: 7 ⁇ aeralkyl group) includes, for example, benzyl, phenethyl, naphthylmethyl, and the like, and” (:: 6 halogenoalkyl group) includes, for example, fluoromethyl, 2-fluoroethyl, Examples thereof include 1,1-difluoroethyl, 2,2,3,3-tetrafluoropropyl pill, etc. “An optionally substituted hydrocarbon group” and “having a substituent” represented by R 1 . These substituents in the “optionally substituted heterocyclic group” are not limited to one, and may be the same or different and may be plural (2 to 4).
  • the heterocyclic group in the xy group, the heterocyclic thio group, the heterocyclic sulfinyl group, the heterocyclic sulfonyl group and the heterocyclic amino group represents a group formed by removing one hydrogen atom bonded to the heterocyclic ring.
  • the heterocyclic ring is a 5- to 8-membered ring containing 1 to several, preferably 1 to 4 hetero atoms such as a nitrogen atom (which may be oxidized), an oxygen atom, and a sulfur atom, or a fused ring thereof. Is shown.
  • heterocyclic group examples include pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, furyl, chenyl, oxazolyl, isoxazolyl, 1,2,3- Oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4_oxadiazolyl, thiazolyl, isothiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2 , 5—Thiadiazolyl, 1,3,4-Thiadiazolyl, pyrrolidinyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, piberidinyl, piperazinyl, indolyl, vilanyl, thioviranyl, dioxinyl, dioxo
  • the “divalent group” in the “divalent group optionally having a substituent” represented by X is X Is one selected from a carbon atom, a nitrogen atom, an oxygen atom, a sulfur atom, and a silicon atom, or two to four atoms connected in series, for example, a divalent hydrocarbon group
  • X Is one selected from a carbon atom, a nitrogen atom, an oxygen atom, a sulfur atom, and a silicon atom, or two to four atoms connected in series for example, a divalent hydrocarbon group
  • lower alkylene methylene, ethylene, propylene, etc.
  • one or two atoms selected from oxygen, nitrogen and sulfur atoms or one or two and lower alkylene selected from oxygen, nitrogen and sulfur atoms (Methylene, ethylene, propylene, etc.) in series.
  • One have a substituent as a divalent group may be for example NR 4 - CH 2 -, - NR 4 - CH 2 CH 2 -, - 0_CH 2 _, -? O- CH CH -?, One S— CH 2 —, -S-CH 2 CH-, one CH 2 — NR 4 — C H 2 — — CH 2 — O— CH 2 — — CH 2 — S— CH 2 — (wherein R 4 has the same meaning as described above.), Among which — NR 4 — CH 2 — (wherein, R 4 has the same meaning as described above.).
  • Examples of the optionally substituted methylene group represented by Y include unsubstituted methylene, 1,1-ethylene, 11-propylene, 22-propylene, 11-butylene, 22- Examples include methylene in which methylene such as butylene is substituted by one or two C 3 alkyl groups.
  • R 4 is preferably a hydrocarbon group which may have a substituent.
  • the hydrocarbon group an alkyl group such as methyl, ethyl, propyl and isopropyl is particularly preferable.
  • salts with inorganic acids, salts with organic acids, salts with acidic amino acids and the like when these compounds have a basic group such as 1 NH 2 as a substituent,
  • inorganic acids include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like.
  • Preferred examples of the salt with an organic acid include, for example, formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid , P-toluenesulfonic acid and the like.
  • Preferable examples of the salt with an acidic amino acid include, for example, salts with aspartic acid, glutamic acid and the like.
  • the compound has an acidic group such as —COOH as a substituent, it may form a salt with an alkali metal such as lithium, sodium, and potassium.
  • the reaction of the present invention is carried out by reacting the compound (I) with an acid anhydride.
  • the acid anhydride include carboxylic anhydride and sulfonic anhydride, but carboxylic anhydride is preferable.
  • Compound (III) is an example of a carboxylic anhydride. I can do it.
  • R 1 the above-mentioned
  • compound (III) include, for example, acetic anhydride, succinic anhydride, phthalic anhydride, propionic anhydride, butyric anhydride, isobutyric anhydride, valeric anhydride, cinnamic anhydride, benzoic anhydride, toluic anhydride, itaconic anhydride Acids, dartaric anhydride, maleic anhydride, citraconic anhydride, daltaconic anhydride, diglycolic anhydride, diphenic anhydride and the like. Among them, acetic anhydride is preferably used.
  • the reaction of the present invention is preferably carried out in the presence or absence of a solvent, usually in the presence of an organic base.
  • the organic base include an organic base having a pKa of 5 or more in an aqueous solution, for example, basic amines.
  • the basic amines include organic cyclic amines and tertiary amines.
  • the organic cyclic amines include trimethylamine and triethylamine.
  • Examples of the tertiary amines include 1,5-diazabicyclo [4.3.0] non-5-ene and 1,4. -Diazabicyclo
  • ethers such as tetrahydrofuran, dioxane, diethyl ether, diisopropyl ether, dimethylene glycol dimethyl ether, diethylene glycol methyl ether, esters such as ethyl acetate, butyl acetate, benzene, toluene, xylene, etc.
  • Aromatic hydrocarbons ketones such as acetone and ethyl methyl ketone, nitriles such as acetonitrile and benzonitrile, hydrocarbons such as cyclohexane, hexane, heptane and pentane, dimethylformamide, dimethyl sulfoxide De, Jimechirua acetamide, to hexa aprotic polar solvents such as triamide Among these, an aprotic polar solvent is preferably used.
  • the amount of the acid anhydride to be used is 0.5 to 20 mol, preferably 1 to 5 mol, per 1 mol of compound (I).
  • the amount of the organic base to be used is generally 5 to 20 mol, preferably 1 to 5 mol, per 1 mol of compound (I).
  • the amount of the solvent to be used is generally 0.1-100 liters, preferably 0.5-5 liters, per 1 mol of compound (I).
  • the compound (I), the acid anhydride, the organic base and the solvent may be mixed in any order.
  • the compound (I), the organic base, the acid anhydride and the solvent are sequentially added.
  • the reaction temperature is usually 0 to 200 ° C, preferably 50 to 90 ° C, and the reaction time is about 0.5 to 20 hours, preferably about 1 to 5 hours.
  • R 1 and X in compound (I) have a functional group such as a hydroxyl group or a carboxyl group in carrying out this reaction, these groups are protected with respective protecting groups in advance, and It is preferred to deprotect after the end of the reaction.
  • a protecting group for the protection and deprotection reactions with such a protecting group, methods generally known in the field of peptide chemistry can be employed.
  • Compound (II), which is the target compound of this reaction can be obtained from the reaction solution by a conventional method, for example, separation, concentration, distillation, crystallization, or a combination thereof.
  • Compound (IV) may be obtained in the above reaction of the present invention.
  • compound (IV) when the reaction is carried out in the presence of a relatively weak base such as triethylamine, compound (IV) is obtained.
  • the acyloxy group represented by Z is an acyloxy moiety of an acid generated from the acid anhydride used.
  • Z is an acetyloxy group.
  • the salt of the compound represented by the formula (IV) include those similar to the salts described as the salt of the compound represented by the formula (I).
  • Compound (IV) can be isolated and purified from the reaction solution by a conventional method, for example, separation, concentration, distillation, crystallization, or a combination thereof.
  • the reaction mixture containing the compound (IV) is Preferably, when the reaction is carried out in the presence of a relatively strong basic amine such as 1,8-diazabicyclo [5.4.0] -7-pandene, the ring is closed to produce the compound (II).
  • X—C ⁇ — has the formula:
  • a 1-2 represent a halogenated phenyl group, (R) represents a steric configuration
  • Y is methylene
  • R 1 has a substituent.
  • the compound which is an aliphatic or aromatic hydrocarbon group which may be optionally substituted or an aromatic bicyclic group which may have a substituent, that is, the compound (C) is a compound having antifungal activity itself, It is used as an active ingredient of pesticides (see JP-A-8-104676).
  • Other compounds (II) may also exhibit antifungal activity by themselves, but can be led to other compounds using a known reaction as appropriate.
  • X is a compound represented by the formula:
  • a compound represented by the formula (V) [hereinafter simply referred to as compound (V)] is converted into a compound represented by the formula (VI) [hereinafter simply referred to as compound (VI)] or a compound represented by the formula (VII)
  • Compound (Ia) can be produced by reacting a compound represented by the following formula [hereinafter referred to as compound (VII)].
  • Examples of the leaving group represented by X 1 include a phenyloxy group, a chlorophenyl group, a nitrophenyl group, and the like. Among them, a phenyloxy group is preferable.
  • the reaction of compound (V) with compound (VI) or compound (VII) is carried out in the presence or absence of a base in a solvent that does not inhibit the reaction or in the absence of a solvent.
  • the compound (VI) or the compound (VII) is preferably reacted in an amount of about 0.5 to 5 mol, preferably about 0.7 to 1.5 mol, per 1 mol of the compound (V). More preferred.
  • examples of the base include inorganic bases (eg, potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, etc.) and organic bases (eg, triethylamine, pyridine, diisopropyleluamine, etc.).
  • Organic bases such as triethylamine and pyridine are particularly preferable.
  • the amount of the base to be used is preferably about 0.5 to 10 times (molar ratio), more preferably about 0.9 to 5 times (molar ratio) based on compound (V). preferable.
  • examples of the solvent include sulfoxides such as dimethyl sulfoxide; ethers such as dimethyl ether, tetrahydrofuran and dioxane; nitriles such as acetonitrile; and aromatic hydrocarbons such as benzene, toluene and xylene.
  • the reaction temperature is suitably about ⁇ 10 to 150 ° C., preferably about 0 to 120 ° C.
  • the reaction time is suitably from about 0.1 to 50 hours, preferably from about 0.5 to 30 hours.
  • Compound (I) which is a starting compound of the present invention, can be synthesized, for example, by a reaction represented by the following formula.
  • Q represents a general protecting group for a hydroxyl group, and other symbols are as defined above.
  • a compound represented by the formula (VIII) [hereinafter, simply referred to as a compound (VI II)]
  • a compound represented by the formula (X) [hereinafter simply referred to as a compound (X)] is synthesized from the compound represented by the formula (IX) by a general amidation reaction, followed by a general deprotection from the compound (X).
  • Compound (I) can be produced by a group reaction.
  • Compound (VIII) is known, for example, ( ⁇ ) -3-hydroxybutyric acid, (R)-(—)-3-hydroxybutyric acid, its sodium salt, DL-3-hydroxybutyric acid, its sodium salt, (S )-(+)-3-Hydroxybutyric acid, its sodium salt, 4-hydroxybutyric acid, its sodium salt, 10-hydroxydecanoic acid, 12-hydroxydodecanoic acid, and 16-hydroxyhexadecanoic acid are commercially available. It is also listed in the catalog published by Aldrich. BEST MODE FOR CARRYING OUT THE INVENTION
  • the reaction solution was cooled to about 30 ° C, and 46 L of ethyl acetate and 30 L of water were added to separate the solution.
  • the organic layer was concentrated, and 32 L of methanol-denatured ethanol and 32 L of water were added to the residue. After cooling, the precipitated crystals were separated by a centrifugal separator, and washed with 13 L of a mixed solution of methanol-modified ethanol-water (1: 1).
  • the reaction solution was cooled to about 30 ° C, and 46 L of ethyl acetate and 30 L of water were added to separate the solution.
  • 30 L of ethyl acetate was added to the aqueous layer to separate the layers.
  • 30 L of ethyl acetate was added to the aqueous layer to carry out liquid separation.
  • the organic layers were combined and washed with 20 L of an aqueous sodium hydroxide solution.
  • the organic layer was heated with 0.11 ⁇ hydrochloric acid, then adjusted to pH 2 to 4 with dilute hydrochloric acid, and separated. 10 L of ethyl acetate was added to the aqueous layer to separate the layers.
  • the organic layers were combined, concentrated, and 32 L of methanol-denatured ethanol and 32 L of water were added to the residue.
  • the mixture was stirred at about 60 ° C for about 1 hour, at about 20 ° C for about 1 hour, and at about 5 ° C for about 1 hour.
  • the precipitated crystals were separated and washed with 13 L of a cooled methanol-denatured ethanol-water (1: 1) mixed solution.
  • the reaction solution was cooled to about 30 ° C., 45 ml of ethyl acetate was added, and 30 ml of water was added for liquid separation.
  • the organic layer was concentrated, and methanol-denatured ethanol was added to the residue at 3 Om, and water (30 ml) was added. After cooling, the precipitated crystals were separated and washed with 1 Om 1 of a mixed solution of methanol-denatured ethanol-water (1: 1).
  • a cyclic amide compound can be produced industrially advantageously.

Abstract

L'invention concerne un procédé de production industrielle avantageux d'un composé représenté par la formule (II), (dans laquelle R1 représente un groupe hydrocarboné éventuellement substitué ou un groupe hétérocyclique éventuellement substitué; X désigne un groupe divalent éventuellement substitué; et Y symbolise un groupe méthylène éventuellement substitué), ou d'un sel de celui-ci. Ce procédé consiste notamment à faire réagir un composé représenté par la formule (I), (dans laquelle R1, X, et Y ont la même signification que ci-dessus), ou un sel de celui-ci, avec un anhydride acide.
PCT/JP1999/006765 1998-12-04 1999-12-02 Procede de production d'un compose d'amide cyclique WO2000034267A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU15126/00A AU1512600A (en) 1998-12-04 1999-12-02 Process for producing cyclic amide compound

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP10/346033 1998-12-04
JP34603398 1998-12-04

Publications (1)

Publication Number Publication Date
WO2000034267A1 true WO2000034267A1 (fr) 2000-06-15

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003086271A3 (fr) * 2002-04-17 2004-02-26 Ranbaxy Lab Ltd Derives azole utilises en tant qu'agents antifongiques

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JPS5139039A (ja) * 1974-09-28 1976-04-01 Mitsubishi Paper Mills Ltd Karaayokankozairyo
GB1547798A (en) * 1975-07-08 1979-06-27 Troponwerke Dinklage & Co N-(3-2-hydroxypropopyl)-4-methyl-2-oxo-2h-1-benzopyran-7-yl)- carboxamide derivatives
EP0008421A2 (fr) * 1978-08-11 1980-03-05 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Benzodiazépines, procédé pour leur préparation et produits pharmaceutiques les contenant
US4418198A (en) * 1981-11-16 1983-11-29 The Dow Chemical Company Substituted pyridine carbonyl amino ethyl esters of 2-methyl-2-propenoic acid
EP0164100A2 (fr) * 1984-06-06 1985-12-11 Polaroid Corporation Polymères pyridinium ylides et produits préparés à partir de ceux-ci
EP0169051A2 (fr) * 1984-07-17 1986-01-22 Eli Lilly And Company Composés de pyridazinylurées
EP0212373A2 (fr) * 1985-08-03 1987-03-04 BASF Aktiengesellschaft Composés photoréactifs
EP0224951A1 (fr) * 1985-11-26 1987-06-10 Agfa-Gevaert N.V. Elément récepteur d'image comprenant des agents anti-altération de couleurs
EP0226947A1 (fr) * 1985-12-21 1987-07-01 Shell Internationale Researchmaatschappij B.V. Nouveaux imidazolinones herbicides
EP0330209A2 (fr) * 1988-02-26 1989-08-30 BASF Aktiengesellschaft Polymères photoréactifs et procédé pour la fabrication d'une réserve à deux couches
US5094765A (en) * 1990-04-30 1992-03-10 Texaco Inc. Lubricating oil composition
JPH0625160A (ja) * 1992-07-10 1994-02-01 Ishihara Sangyo Kaisha Ltd 環状アミド系化合物、それらの製造方法及びそれらを含有する除草剤
WO1995033719A1 (fr) * 1994-06-02 1995-12-14 Zeneca Limited Pyrrolidone, thiazolidones ou oxazolidones substitues utilises comme herbicides
WO1996025410A1 (fr) * 1995-02-17 1996-08-22 Takeda Chemical Industries, Ltd. Production et utilisation de composes de type azole

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3786058A (en) * 1971-03-29 1974-01-15 Ici Ltd Certain bis(pyridinium quaternary salts)
US3907782A (en) * 1971-03-29 1975-09-23 Ici Ltd Fumaramido bis(pyridinium salts)
JPS5139039A (ja) * 1974-09-28 1976-04-01 Mitsubishi Paper Mills Ltd Karaayokankozairyo
GB1547798A (en) * 1975-07-08 1979-06-27 Troponwerke Dinklage & Co N-(3-2-hydroxypropopyl)-4-methyl-2-oxo-2h-1-benzopyran-7-yl)- carboxamide derivatives
EP0008421A2 (fr) * 1978-08-11 1980-03-05 F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft Benzodiazépines, procédé pour leur préparation et produits pharmaceutiques les contenant
US4418198A (en) * 1981-11-16 1983-11-29 The Dow Chemical Company Substituted pyridine carbonyl amino ethyl esters of 2-methyl-2-propenoic acid
EP0164100A2 (fr) * 1984-06-06 1985-12-11 Polaroid Corporation Polymères pyridinium ylides et produits préparés à partir de ceux-ci
EP0169051A2 (fr) * 1984-07-17 1986-01-22 Eli Lilly And Company Composés de pyridazinylurées
EP0212373A2 (fr) * 1985-08-03 1987-03-04 BASF Aktiengesellschaft Composés photoréactifs
EP0224951A1 (fr) * 1985-11-26 1987-06-10 Agfa-Gevaert N.V. Elément récepteur d'image comprenant des agents anti-altération de couleurs
EP0226947A1 (fr) * 1985-12-21 1987-07-01 Shell Internationale Researchmaatschappij B.V. Nouveaux imidazolinones herbicides
EP0330209A2 (fr) * 1988-02-26 1989-08-30 BASF Aktiengesellschaft Polymères photoréactifs et procédé pour la fabrication d'une réserve à deux couches
US5094765A (en) * 1990-04-30 1992-03-10 Texaco Inc. Lubricating oil composition
JPH0625160A (ja) * 1992-07-10 1994-02-01 Ishihara Sangyo Kaisha Ltd 環状アミド系化合物、それらの製造方法及びそれらを含有する除草剤
WO1995033719A1 (fr) * 1994-06-02 1995-12-14 Zeneca Limited Pyrrolidone, thiazolidones ou oxazolidones substitues utilises comme herbicides
WO1996025410A1 (fr) * 1995-02-17 1996-08-22 Takeda Chemical Industries, Ltd. Production et utilisation de composes de type azole

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003086271A3 (fr) * 2002-04-17 2004-02-26 Ranbaxy Lab Ltd Derives azole utilises en tant qu'agents antifongiques

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