WO1994017059A1 - Heterocyclic derivative - Google Patents

Heterocyclic derivative Download PDF

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Publication number
WO1994017059A1
WO1994017059A1 PCT/JP1994/000109 JP9400109W WO9417059A1 WO 1994017059 A1 WO1994017059 A1 WO 1994017059A1 JP 9400109 W JP9400109 W JP 9400109W WO 9417059 A1 WO9417059 A1 WO 9417059A1
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Prior art keywords
ome
substituted
alkyl
bruno
compound
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PCT/JP1994/000109
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French (fr)
Japanese (ja)
Inventor
Yasuyuki Miyazawa
Yoshihiko Hara
Akiyoshi Ueda
Masami Koguchi
Kazuyuki Tomida
Takashi Kawana
Original Assignee
Nippon Soda Co., Ltd.
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Application filed by Nippon Soda Co., Ltd. filed Critical Nippon Soda Co., Ltd.
Priority to AU58914/94A priority Critical patent/AU5891494A/en
Publication of WO1994017059A1 publication Critical patent/WO1994017059A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/66—1,3,5-Triazines, not hydrogenated and not substituted at the ring nitrogen atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/713—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with four or more nitrogen atoms as the only ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/22—O-Aryl or S-Aryl esters thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to a novel heterocyclic derivative, a method for producing the same, and a herbicide containing the derivative as an active ingredient.
  • Herbicides are being used. However, there is a need for the development of drugs that can be used safely and safely at lower doses because they cause phytotoxicity, remain in the environment, and pollute crops.
  • rr 2 is a lower alkyl group, a lower alkoxy group, etc.
  • r 3 is a lower alkyl group, etc.
  • X 2 is 0 or S
  • a! Is CH or N
  • y 1, y 2 and y 3 are H, etc.
  • bi is CH or N.
  • An object of the present invention is to provide a herbicide which can be synthesized industrially advantageously, is effective at a lower dose, has high safety, and has high crop selectivity.
  • the present invention has the general formula (1)
  • A represents a nitrogen atom or a carbon atom substituted by R 3 ;
  • B represents a nitrogen atom or a carbon atom substituted by hydrogen or X;
  • Z represents oxygen, optionally oxidized sulfur, optionally substituted nitrogen, or optionally substituted carbon atom,
  • Q represents a 5- to 6-membered heterocyclic ring containing 1 to 4 nitrogen, oxygen or sulfur, and is bonded to a benzene or pyridin ring at the carbon atom of Q;
  • R, R 2 are each independently hydrogen, d-4 alkyl, d-4 alkoxy, C, - 4 haloalkoxy, haloalkyl, C, - 4 Arukiruami Bruno, current events ⁇ alkyl Ruami Bruno, C, - 4 alkylthio, Represents a halogen or cyano group,
  • R 3 represents hydrogen, d-alkyl, halogen, nitro, formyl, or acyl; R 2 and R 3 may be taken together to form a ring;
  • X, Y are each independently hydrogen, CI- e alkyl, C 3 - 7 cycloalkyl, C 2 - e ⁇ alkenyl, C haloalkyl, C 2 - 6 alkynyl, halogen, nitro, ⁇ Mi Roh, C Arukiruami Bruno, Ashiruami Bruno, CI- 6 alkylsulfonyl ⁇ Mi Bruno, formyl, Ashiru, Shiano, carboxyl, 'I Mi Bruno, human Dorokishiru, Ci - 6 an alkoxy carbonyl, C -!
  • Examples of the 5- to 6-membered heterocyclic ring containing 1 to 4 nitrogen, oxygen, or sulfur of Q include, for example, imidazole, isoxazole, oxazole, oxaziazole, pyrrol, pyrazole, thiazol, thiadiazole, and tereazole.
  • Examples include tolazole, triaryl, dithiazole, pyrimidine, pyridine, pyrazine, oxazine, pyridazine, pyrone, triazine, and dihydro forms of these heterocycles.
  • Y, ⁇ 55 is hydrogen, d-alkyl, C 3 - 7 cycloalkyl, C 2 one 6 alkenyl, haloalkyl, C 2 _ 6 alkynyl, halogen, two Toro, amino, Arukiruami Bruno, Ashiruami Bruno , d alkylsulfonyl ⁇ Mi Bruno, formyl, Ashiru, Shiano, carboxyl, I Mi Bruno, human Dorokishiru, C i-6 alkoxide aryloxycarbonyl, C alkoxy, which may be substituted Benjiruokishi, C 2 - 6 Arukeniruokishi, C i haloalkoxy, C 2 -alkynyloxy, optionally substituted phenoxy, optionally substituted benzyl, aminoxy, C 6 alkylthio, optionally substituted phenyl, alkylsulfonyl, optionally substituted Fuweniruchio,
  • two ⁇ , to Y 55 may form a carbocyclic or heterocyclic ring. ] And so on. And, preferably, Q-Upsilon eta,
  • D 2 When D, is N, D 2 represents NY or 0,
  • Q is particularly preferably an oxazole-5-yl or 2-oxazoline-5-yl group.
  • benzyloxy, phenoxy, benzyl, phenyl, phenylthio, benzoyl, phenylsulfonyl, heterocyclic-oxy, and heterocyclic monothio groups may be substituted by de alkoxy, C, -s alkyl, Halogen, nitro
  • the compound of the present invention can be produced by the following method.
  • the 0-heterocyclic-substituted phenol (or hydroxypyridin) derivative [3] as a raw material in the above reaction can be produced by the method described below.
  • solvents used in the following reactions include alcohols such as methanol, ethanol, and isopropyl alcohol, aromatic hydrocarbons such as benzene and toluene, dichloromethane, and chloroform.
  • C such as mouth holm Hydrogenated hydrocarbons, ethers such as getyl ether and THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, non-protonic polar solvents such as DMF and DMS 0,
  • ethers such as getyl ether and THF
  • ketones such as acetone and MEK
  • esters such as methyl acetate and ethyl acetate
  • non-protonic polar solvents such as DMF and DMS 0
  • Examples include nitriles such as cetonitrile, water and the like.c.
  • Examples of the base used include sodium carbonate, carbonate such as carbonated carbonate, sodium hydroxide, hydroxylated phosphate and the like.
  • Metal hydroxides such as sodium hydroxide, sodium methylate, sodium methylate, etc., metal hydrides such as sodium hydride, alkyl metals such as butyl lithium, lithium diisopropylamide, lithium bismuth Examples thereof include lithium amides such as rimethylsilylamide, and organic bases such as triethylamine and DBU.
  • the acid to be used include mineral acids such as hydrochloric acid, nitric acid, and sulfuric acid, organic acids such as formic acid and acetic acid, and Lewis acids such as aluminum chloride and boronant fluoridated getyl ether.
  • the reaction temperature may be from 190 ° C. to the boiling point of the solvent or lower. (Hereinafter, X, m, and B represent the same meaning as described above.)
  • a compound in which Q is imidazole-41-yl can be produced by reacting imine [7] with Tos MIC (p-toluenesulfonylmethyl isocyanide) in the presence of a base.
  • Tos MIC p-toluenesulfonylmethyl isocyanide
  • the compound [3f] in which Q is 1,3,4-triazol_2-2-yl is obtained by converting the compound [8] to acid chloride or an acid anhydride in DMF at 0 to 120 ° C. It can be produced by reacting with.
  • R 5 represents an alkyl, aryl or CF 3 group.
  • 3-position substitution-1,3,4_triazole-2-yl derivative [3g] is the teaching of J. 0rg. Chem. 4 Volume 4, 4160 pages (1977) Then, the amide [9] is reacted with dimethylformamide and dimethylacetal to synthesize N-[(dimethylamino) methylene] amide [10]. Hydrazines react with [10] To induce Triazole [11]. When L 2 is a methoxymethoxy or benzyloxy group, [11] is treated with an acid, or [3 g] is obtained by a hydrogenolysis reaction using palladium carbon or the like as a catalyst.
  • [3h] is obtained by reacting tin azide with [13] according to the method described in J. Org. Chem. 56, pp. 2395 (1991). Can also be manufactured.
  • a derivative in which Q is thiazol-2-yl is synthesized as follows.
  • the thioamide [15] and the promotone [16] are reacted in an alcohol at 25 to 80 ° C for 1 to 20 hours to synthesize [17].
  • [3i] is produced by performing the same reaction as in the production method of [17] to [3g].
  • R 8 represents alkyl, ⁇ reel, CF 3 group
  • R g represents hydrogen, alkyl, COOR 10 group
  • R 10 represents alkyl group
  • L 2 and RT have the same meanings as above. Represents.
  • the derivative [3j] of Q is thiazole-4-yl is obtained by reacting [19] with the promotone [18] in an alcohol at 25 to 80 for 1 to 20 hours to form a thiazole ring. After being formed, it is produced by performing the same reaction as in the production method of [3 g].
  • R 12 represents alkyl, aryl, R 13 NH group
  • R 13 represents hydrogen, alkyl, aryl group
  • L 2 , R 7 and R 10 represent the same meaning as described above.
  • the derivative [3k] of thiazol-5-yl for Q can also be produced by the same method as described above.
  • R 14 represents hydrogen or an alkyl group
  • L 2 , R 7 , and R 12 represent the same meaning as described above.
  • the derivative [31] of Q is oxazole-2-yl is obtained by reacting the amide [9] with the promoketone [23] at 50 to 160 ° C for 1 to 48 hours with [24]. After that, the reaction can be carried out in the same manner as in the production method of [3 g].
  • R 15 represents a hydrogen, alkyl, phenyl or CF 3 group
  • R 16 represents a hydrogen, an alkyl or phenyl group
  • L 2 and R 7 have the same meanings as described above.
  • oxazole-4-yl Derivative of oxazole-4-yl is also obtained by the same reaction as (31) .c Compound (27) and amide (28) are reacted at 50 to 160 ° C for 1 to 48 hours. After obtaining the oxazole derivative [29], [3n] can be produced by performing the same reaction as in the production method of [3g] from [29].
  • L 3 represents halogen
  • R 17 represents hydrogen, methyl, ethyl group, COOR 10
  • R 18 represents hydrogen, alkyl, phenyl group
  • L 2 , R 7 , R 10 Represents the same meaning as described above.
  • R 22 H, Alkyl, CH 2 Ph or Nitro
  • the derivative [3r] of Q is oxazole-5-yl can also be produced by the following method. That is, by reacting isonitrile [38] with aldehyde [37] in the presence of a base such as sodium carbonate hydride at 25 to 100 for 0.5 to 8 hours. [9], followed by the same reaction as in [3 g].
  • a base such as sodium carbonate hydride
  • R 22 represents a hydrogen, an alkyl, or a benzyl group
  • L 2 and R 7 represent the same meaning as described above.
  • R 23 H, Alkyl, Halogen
  • the derivative [3s] of Q is a condensed oxazole-2-yl is prepared by reacting compound [40] with thiominophenol [41] to give compound [4 2] via compound [42]. It is produced by performing the same reaction as described above.
  • R 23 represents hydrogen, an alkyl group, or halogen, and L 2 and R 7 have the same meanings as described above.
  • Derivative [3x] of Q isoxazole-4-yl is obtained by converting compound [44] into formylolate to form [45], cyclizing with hydroxylamine, and finally phenol. It is produced by removing the protecting group. References for this reaction include Pharmaceutical Journal, Vol. 79, p. 623 (1959). (In the formula, R 24 represents a hydrogen, alkyl, or funinyl group.)
  • (3y) can be produced by reacting benzofuran [47] with hydroxylamine in alcohol at 25 to 80 ° C for 0.5 to 8 hours,
  • 1,2,4-oxaziazol-5-yl derivative [3z] is obtained by converting [34] and amidoxime [48] in the presence of a base in the range of 1 to 8 at 0 to 140 ° C. After reacting for 4 hours to obtain [49], the same reaction as in the production method of [3 g] is performed, It is.
  • R 25 represents hydrogen, alkyl, benzyl, aryl, haloalkyl, alkoxyalkyl, or alkylthioalkyl, and L 2 and R 7 have the same meanings as described above.
  • the derivative of pyrrolyl-3-yl [3c '] is obtained by converting ketone [52] to oxime [53], and then cyclizing it with an acetylene compound to form a pyrrole ring. And then performing the same reaction as in the production method of [3 g].
  • R 26 and R 27 each represent a CN, COORio> phenyl group, and L 2 and R 10 have the same meaning as described above.
  • ketone [55] By reacting ketone [55] with glyoxylic acid and hydrazine, a derivative of 3-pyridazinone-6-yl [3d '] can be produced.
  • the compound represented by the general formula [1] can also be produced by the following method.
  • the compound can be produced by a method similar to the method for synthesizing compound [3] described above. That is, this is a method for producing [1] by reacting a compound represented by the general formula [56] with an appropriate condensing agent shown in the production method of the above [3].
  • R 29 H, Alkyl, CH 2 Ph, Aryl, C00R IO , represents the group shown in Tos. L ⁇ LS. R ⁇ . RU. R. R. R ⁇ has the same meaning as described above.
  • the compound represented by the general formula [57] and sodium azide are mixed in a suitable solvent, preferably using DMF, at a temperature from room temperature to a temperature lower than the boiling point of the solvent, preferably 80 to 120 to 1-. Manufactured by reacting for 24 hours. (Hereinafter, in the formula, R,, R 2 , A, B, Z, X, and m have the above meanings.) N /: i ⁇
  • Examples of the solvent used for this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; Ethers such as ether, THF, etc., ketones such as acetate, MEK, etc., esters such as methyl acetate, ethyl acetate, non-protonic polar solvents such as DMF and DMS 0, acetonitrile, water, etc.
  • Bases used in this reaction include carbonates such as sodium carbonate and potassium carbonate, sodium hydroxide, metal hydroxides such as hydroxylating lime, sodium methylate and sodium ethylate.
  • Metal hydrides such as sodium hydride, hydrogen hydride, lithium amides such as lithium diisopropylamide, lithium bistrimethylsilylamide, triethylamine, DBU, etc. Organic bases and the like.
  • the compound represented by the general formula (60) is reacted with T 0 s MIC in a suitable solvent in a suitable solvent at a temperature from room temperature to a temperature lower than the boiling point of the solvent for 1 to 24 hours. It is manufactured by having
  • solvent used in this reaction examples include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; Ethers, ethers such as THF, ketones such as acetone, MEK, methyl acetate., Ethyl acetate 109
  • Esters such as 27, non-protonic polar solvents such as DMF and DMS 0, and acetonitrile-water.
  • the base used in this reaction include sodium carbonate, carbonate such as sodium carbonate, sodium hydroxide, metal hydroxide such as sodium hydroxide, sodium methylate, and sodium hydroxide.
  • Metal alcohols such as lithium ethylate; metal hydrides such as sodium hydride and potassium hydride; lithium amides such as lithium diisopropylamide and lithium bistrimethylsilyl amide;
  • Organic bases such as triethylamine and DBU are exemplified.
  • the compound represented by the general formula [61] is reacted with a hydrazine in the presence or absence of a suitable base in a suitable solvent at a temperature from room temperature to a temperature lower than the boiling point of the solvent for 1 to 24 hours.
  • a suitable base in a suitable solvent at a temperature from room temperature to a temperature lower than the boiling point of the solvent for 1 to 24 hours.
  • the solvent used in this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; and halogenated hydrocarbons such as dichloromethane and chloroform.
  • Ethers such as getyl ether and THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, non-protonic polar solvents such as DMF and DMSO, acetonitrile, and water And the like.
  • the base used in this reaction include sodium carbonate, carbonate such as carbonated lime, sodium hydroxide, metal hydroxide such as hydroxylated lime, sodium methylate and sodium methacrylate.
  • Metal hydrides such as sodium hydride, hydrogen hydride, etc .; lithium amides such as lithium diisopropylamide and lithium bistrimethylsilyl amide; and triethylamid And organic bases such as DBU.
  • the compound represented by the general formula [62] and the promoketone [16] are reacted with a suitable base in the presence or absence of a suitable base in a suitable solvent at a temperature from room temperature to a temperature lower than the boiling point of the solvent, from 1 to 24. It is manufactured by reacting for hours.
  • Examples of the solvent used in this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; Examples include ethers such as THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, non-protonic polar solvents such as DMF and DMSO, and acetonitrile.
  • the base used in this reaction includes sodium carbonate, carbonated carbonate and the like, sodium hydroxide-hydroxide hydroxide and other metal hydroxides, and sodium methyler.
  • Metal alkoxides such as sodium and sodium hydride, metal hydrides such as sodium hydride and hydrogen hydride, lithium amides such as lithium diisopropylamide, and organic bases such as triethylamine and DBU. And the like. (In the formula, R 8. R 8 represents the same meaning as described above.)
  • the aldehyde represented by the general formula [63] and the isonitrinole [38] are reacted with the aldehyde in the presence of at least two equivalents of a suitable base in a suitable solvent at room temperature to below the boiling point of the solvent. It is produced by reacting at a temperature for 1 to 24 hours.
  • Solvents used in this reaction include, for example, alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; dimethyl ether; Examples include ethers such as THF, non-protonic polar solvents such as DMF and DMS0, and acetonitrile.
  • Examples of the base used in this reaction include carbonates such as sodium carbonate and potassium carbonate, metal hydroxides such as sodium hydroxide and hydroxide rim, sodium methylate, sodium methylate and the like.
  • Solvents used in this reaction include, for example, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as dichloromethane and chloroform, ethers such as getyl ether and THF, DMF, DM Non-protonic polar solvents such as S0 and acetonitril.
  • the base used in this reaction includes sodium carbonate, sodium carbonate and the like, sodium hydroxide, metal hydroxide such as sodium hydroxide, sodium hydride, hydrogen hydride and the like.
  • Metal hydrides such as lithium, lithium amides such as lithium diisopropylamide and lithium pristylmethylsilylamide, organic salts such as triethylamine and DBU, and the like. (Wherein, R 20 represents the same meaning as described above.)
  • the aldehyde represented by the general formula [63] and isonitrile [38] are reacted in a suitable solvent in the presence of a suitable base in an amount equivalent to the aldehyde at a temperature of 0 ° C to room temperature.
  • [1j] is produced by reacting for 1 to 2 hours.
  • the solvent used in this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chromatoform; and dimethyl ether.
  • ethers such as THF, non-protonic polar solvents such as DMF and DMSO, and acetonitrile.
  • Examples of the base used in this reaction include carbonates such as sodium carbonate and potassium carbonate, metal hydroxides such as sodium hydroxide and hydrating power, sodium hydride, potassium hydride and the like.
  • acylimidazole represented by the general formula [64] and the amide oxime [48] are reacted in a suitable solvent in the presence of a suitable base at a temperature of 15 to 140 ° C for 1 to 24 hours. This produces [lk].
  • Solvents used in this reaction include, for example, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as dichloromethane and chloroform, ethers such as getyl ether and THF, DMF, Non-protonic polar solvents such as DMSO, acetonitril, and the like.
  • Examples of the base used in this reaction include carbonates such as sodium carbonate and potassium carbonate, metal hydroxides such as sodium hydroxide and hydroxide hydroxide, sodium hydride, and hydrogen.
  • Metal hydrides such as potassium iodide, and lithium such as lithium diisopropylamide Examples include amides, triethylamine, and organic bases such as DBU. (Wherein, R 25 has the same meaning as described above.)
  • the compound represented by the general formula [1 '] is reacted with a suitable base or acid in the absence of a solvent or in a suitable solvent at a temperature of from 178 ° C to a temperature lower than the boiling point of the solvent, according to a method known in the literature.
  • (11) is produced by reacting the compound of the general formula (1j) with (65) in the presence of a suitable base in a suitable solvent at a temperature of 15-25 for 1 to 24 hours.
  • c is a solvent used in this reaction, for example, alcohols such as methanol, ethanol and isoprene Robanoru, benzene, aromatic hydrocarbons such as toluene, dichloroethylene Rorometan, halogenated hydrocarbons such as black hole Holm , Jettlätel, TH
  • ethers such as F
  • ketones such as acetone and MEK
  • esters such as methyl acetate and ethyl acetate
  • non-protonic polar solvents such as DMF and DMS 0, acetonitrile, and water.
  • Examples of the base used in this reaction include sodium carbonate, carbonates such as carbonated lime, sodium hydroxide, metal hydroxides such as hydroxylated lime, sodium methylate, and sodium methylate.
  • Metal alcohols such as triethyl ethylate; metal hydrides such as sodium hydride and potassium hydride; lithium amides such as lithium diisopropyl amide and lithium p-methylsilyl amide
  • organic bases such as triethylamine and DBU.
  • a compound of the general formula [2] (wherein, R,, R 2 , A and L represent the same meaning as described above); and a compound of the general formula [66] (where B, Q, X, Y, m and n represent the same meaning as described above.) in an organic solvent in the presence of a base.
  • a base include metal hydrides such as sodium hydride, carbonates such as potassium carbonate, and organic bases such as triethylamine.
  • the solvent include DMF, DMS0, THF, and DME.
  • the 0-heterocyclic-substituted thiol (or mercapto pyridine) derivative [66] as the raw material in the above reaction can be produced by the method described below.
  • solvents used in the following reactions include alcohols such as methanol, ethanol, and isopropyl alcohol, aromatic hydrocarbons such as benzene and toluene, dichloromethane, and chloroform.
  • Halo such as mouth form Genated hydrocarbons, ethers such as getyl ether and THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, and non-protonic polar solvents such as DMF and DMS O And nitriles such as acetonitril, and water.
  • the base to be used include carbonates such as sodium carbonate and carbonated carbonate, sodium hydroxide, metal hydroxides such as hydroxided sodium, sodium methylate, and sodium ethylate.
  • Metal alcohols such as metal, hydrogenated metals such as sodium hydride, alkyl metals such as butyllithium, lithium amides such as lithium diisopropylamide and lithium bistrimethylsilylamide And organic bases such as triethylamine, DBU and the like.
  • the acid used include mineral acids such as hydrochloric acid, nitric acid and sulfuric acid, organic acids such as formic acid and acetic acid, aluminum chloride, and Lewis acids such as boron trifluoride dodecyl ether.
  • the reaction temperature is, for example, a temperature of 190 ° C to 250 ° C. (Hereinafter, Q, X, Y, m, n, and B represent the same meaning as described above.)
  • Compound (66) can be produced by reacting a compound of the general formula (68) with sodium sulfide or thioperia, which can be produced by a method similar to the method for synthesizing compound (3) described above. I can do it. References for this reaction include Chemistry Letters, page 1307 (1985).
  • [66] is obtained by deriving the above-mentioned compound [3] to [69], and then applying the method described in J. 0 rg. Chem. 31 Volume 1, p. 398 (1966)
  • the compound can also be produced by hydrolyzing this as [70] by the Newman rearrangement reaction described in (1).
  • aniline derivative [71] was converted to 0 r g a n i c S y n t h e se s C o l
  • [66] can also be produced by applying the method described in 1 ect., Volume 3, page 809. (In the formula, L 4 represents halogen, preferably fluorine.)
  • a compound of the general formula [72] (wherein R,, R 2 , A and Z represent the same meaning as described above), and a compound of the general formula [68] (where B, Q, X, Y , m, n, L 4 is a compound of representing.) as defined above, is the presence coupling base in an organic solvent.
  • the base include metal hydrides such as sodium hydride, carbonates such as carbonated lime, and organic bases such as tritylamine.
  • the solvent include DMF, DMS O, THF, and DME. .
  • the reaction mixture is stirred at 0-90 ° C, optionally at 120 ° C, until the reaction is complete.
  • Examples of the salt of the compound represented by the general formula [1] include environmentally acceptable salts, for example, inorganic acid salts such as hydrochloric acid salt and hydrogen bromide salt, and organic acid salts such as acetate, oxalate, and formate. And alkaline metals, alkaline earth metals, ammonium salts and the like. These salts can be prepared in a conventional manner.
  • the structure of the compound of the present invention was determined from IR, NMR, MS and the like.
  • Triethylamine (0.07 g) was added to a methylene chloride solution of 0.15 g of 5- (2- (4,6-dimethoxypyrimidine-12-yloxy) -16-hydroxyphenyl) oxazole. The reaction was stirred at room temperature and after 15 minutes cyclohexyliso 0.08 g of cyanate was added. After stirring for 1.5 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the obtained oil was recrystallized from a mixed solvent of n-hexane and diethyl ether. Thus, 0.17 g of the desired product was obtained.
  • the compound of the present invention or a salt thereof exhibits a high herbicidal activity under any conditions of upland cropping in any of soil treatment and foliage treatment.
  • foliar spray treatment has a high efficacy against various field weeds such as mexican, california, strawberry, and inubu, and also contains compounds that have selectivity for crops such as corn, wheat, soybeans, and ivy.
  • the compound of the present invention or a salt thereof has an excellent herbicidal activity against weeds such as paddy field weeds such as Nobie, Tamagayari, Omodaka and Houyui, and also includes a compound showing selectivity to rice.
  • the compound of the present invention or a salt thereof can also be applied to the control of weeds in orchards, lawns, track ends, vacant lots and the like.
  • the compound of the present invention or a salt thereof includes those having a plant growth regulating action.
  • the herbicide of the present invention contains one or more of the compound represented by the general formula [1] or a salt thereof as an active ingredient, and has a form similar to that of a general pesticide. That is, the active ingredient compound is generally used in the form of a wettable powder, an emulsion, a granule, a water solvent, a flowable or the like by mixing an appropriate amount with a carrier.
  • the solid carrier include talc, white carbon (silicone force), bentonite, clay, and diatomaceous earth.
  • liquid carrier examples include water, alcohol, benzene, xylene, kerosene, mineral oil, cyclohexane, and the like. Cyclohexanone, dimethylformamide and the like are used. In these preparations, a surfactant may be added if necessary to obtain a uniform and stable form.
  • the active ingredient concentration in the herbicide of the present invention varies depending on the form of the preparation described above.
  • a wettable powder it is 5 to 90%, preferably 10 to 85%. %: 3 to 70%, preferably 5 to 30% in the emulsion: 0.01 to 30%, preferably 0.05 to 10% in the granule
  • the concentration is used.
  • the wettable powder and emulsion thus obtained are diluted with water to a predetermined concentration to form a suspension or emulsion, and the granules are directly sprayed or mixed before or after germination of the weeds. .
  • an appropriate amount of 0.1 g or more of the effective component per 10 is applied.
  • the herbicide of the present invention can also be used by mixing with known fungicides, insecticides, acaricides, herbicides, plant growth regulators and the like. In particular, it is possible to reduce the amount of drug used by mixing and using herbicides. In addition to saving labor, higher effects can be expected due to the synergistic action of the mixed drug. In that case, a combination with a plurality of known herbicides is also possible.
  • Suitable agents to be used in combination with the herbicide of the present invention include acid amides such as carbamate herbicides such as benthiocarb, molinate and dimepirate, tiocarbamate herbicides, butachlor, pretilachlor, mefenacet and the like.
  • Herbicides diphenyl ether herbicides such as chrometoxynil and bifenox; triazine herbicides such as atrazine and cyanadine; sulfonylurea herbicides such as chlorsulfuron and sulfometurone monomethyl; MCP, MCPB Carboxylic acid-based herbicides such as diclohop-methyl, etc., phenoxyphenoxypropionic acid-based herbicides such as diclohop-methyl, and pyridyloxy-benzooxypropionic acid-based herbicides such as fluazifop-butyl, and benzoylprop Benzyl, etc.
  • Minopropionic acid herbicides imidazoline and other imidazolinone herbicides, and other products such as piperophos, dimelone, benzozone, difenzocoat, nabroanilide, and HW-52 (4-ethoxyethoxybenz-1) 2,3-Dichloranilide), triazophenamide, kink-mouth lac, and cyclohexanedione-based herbicides such as sethoxydim and aroxydim-sodium. Vegetable oils and oil concentrates can also be added to these combinations.
  • the soil was filled in a pot of 200 cm 2 , and seedlings of Meishishiba, Karyarigusa and Inubu were sown on the surface layer, and after lightly covering the soil, they were grown in a greenhouse.
  • the emulsion of each test compound was diluted with water and adjusted to a concentration of 400 ppm. (equivalent to 400 g per a) and sprayed on the foliage of weeds with a small sprayer.
  • the weed herbicidal effect was investigated according to the following criteria, and the results are shown in Table 32 below. Survey criteria
  • the numbers 1, 3, 5 7 9 represent the intermediate values between 0, 22, and 4, 4 and 6, 6, 6, 8, 8, and 10, respectively.

Abstract

A compound having improved herbicidal and plant growth regulating effects and represented by general formula (1), wherein A represents nitrogen or R3-substituted carbon; B represents nitrogen or carbon which may be substituted by X; Z represents oxygen, optionally oxidized sulfur, nitrogen or carbon; Q represents a 5- or 6-membered heterocycle having one to four nitrogen, oxygen or sulfur atoms, and is bonded to the benzene or pyridine ring via its carbon atom; R1 and R2 represent each hydrogen, alkyl, alkoxy, haloalkoxy, haloalkyl, alkylamino, dialkylamino, alkylthio, halogen or cyano; R3 represents hydrogen, alkyl, halogen, nitro, formyl or acyl, or alternatively R2 and R3 may be combined together to form a ring; X and Y represent each hydrogen, alkyl, cycloalkyl, alkenyl, haloalkyl, alkynyl, halogen, nitro, amino, alkylamino, etc.; and m and n represent each an integer of 1 to 4.

Description

明  Light
複素環誘導体 Heterocyclic derivatives
技術分野： Technical field:
本発明は、 新規な複素環誘導体、 その製造方法及び該誘導体を有効成分として 含有する除草剤に関するものである。  The present invention relates to a novel heterocyclic derivative, a method for producing the same, and a herbicide containing the derivative as an active ingredient.
背景技術： Background technology:
農園芸作物の栽培にあたり、 多大の労力を必要としてきた雑草防除に多くの除 田  Many cultivation of agricultural and horticultural crops requires a lot of labor.
草剤が使用されるようになってきた。 しかし作物に薬害を生じたり、 環境に残留 したり、 汚染したりすることから、 より低い薬量で効果が確実でしかも安全に使 用できる薬剤の開発が望まれている。 Herbicides are being used. However, there is a need for the development of drugs that can be used safely and safely at lower doses because they cause phytotoxicity, remain in the environment, and pollute crops.
本発明化合物に関連するピリ ミジルォキシ置換サリチル酸及びその硫黄同族体 は、 文献 （例えば、 特開昭 5 9— 5 9 6 6 9、 特開昭 6 2— 1 7 4 0 5 9、 特開 平 3— 2 3 2 8 8 4、 特開平 4 - 7 7 4 8 7 ) に記載されているが、 選択性も含 めた除草剤としては満足すべきものではない。 また下記化合物が、 特開平 5 — 2 0 2 0 3 8 ( 1 9 9 3年 8月 1 0日発行） に除草作用を有することが記載され ている。  Pyrimidyloxy-substituted salicylic acids and their sulfur homologues related to the compounds of the present invention are described in the literature (for example, JP-A-59-56969, JP-A-62-174059, — 2 3 2 8 8 4, Japanese Patent Application Laid-Open No. 4-7 7 4 8 7), but it is not satisfactory as a herbicide including selectivity. Also, Japanese Patent Application Laid-Open No. 5-22038 (published on August 10, 1993) discloses that the following compounds have a herbicidal action.
、 ' r i
Figure imgf000003_0001
The 'ri
Figure imgf000003_0001
〔式中、 r r 2 は低級アルキル基、 低級アルコキシ基等、 r 3 は低級アル キル基等、 X 2 は 0または S、 a！ は C Hまたは N , y 1 , y 2 及び y 3 は H等、 b i は C H， Nを表す。 〕 ' [In the formula, rr 2 is a lower alkyl group, a lower alkoxy group, etc., r 3 is a lower alkyl group, etc., X 2 is 0 or S, a! Is CH or N, y 1, y 2 and y 3 are H, etc., and bi is CH or N. '
発明の開示： DISCLOSURE OF THE INVENTION:
本発明の目的は工業的に有利に合成でき、 より低い薬量で効果の確実な安全性 の高い、 作物との選択性の良い除草剤を提供することである。 本発明は、 一般式 〔 1〕 An object of the present invention is to provide a herbicide which can be synthesized industrially advantageously, is effective at a lower dose, has high safety, and has high crop selectivity. The present invention has the general formula (1)
〔 1〕
Figure imgf000004_0001
[1]
Figure imgf000004_0001
〔式中、 Aは窒素原子、 もしく は R3 で置換された炭素原子を表し、 Wherein A represents a nitrogen atom or a carbon atom substituted by R 3 ;
Bは窒素原子、 又は水素もしく は Xで置換された炭素原子を表し、  B represents a nitrogen atom or a carbon atom substituted by hydrogen or X;
Zは酸素、 酸化されていても良い硫黄、 置換されていても良い窒素、 又は置換 されていても良い炭素原子を表し、  Z represents oxygen, optionally oxidized sulfur, optionally substituted nitrogen, or optionally substituted carbon atom,
Qは窒素、 酸素もしく は硫黄を 1〜4個含む 5 ~ 6員の複素環を表し、 かつ Q の炭素原子でベンゼン環もしく はピリ ジン環部と結合しており、  Q represents a 5- to 6-membered heterocyclic ring containing 1 to 4 nitrogen, oxygen or sulfur, and is bonded to a benzene or pyridin ring at the carbon atom of Q;
R ， R2 は各々独立して水素、 d-4 アルキル、 d— 4 アルコキシ、 C,—4 ハロアルコキシ、 ハロアルキル、 C,-4 アルキルァミ ノ、 ジじ ^ アルキ ルァミ ノ、 C, - 4 アルキルチオ、 ハロゲン、 シァノ基を表し、 R, R 2 are each independently hydrogen, d-4 alkyl, d-4 alkoxy, C, - 4 haloalkoxy, haloalkyl, C, - 4 Arukiruami Bruno, current events ^ alkyl Ruami Bruno, C, - 4 alkylthio, Represents a halogen or cyano group,
R3 は水素、 d アルキル、 ハロゲン、 ニ トロ、 ホルミル、 ァシル基を表し、 又、 R2 と R3 は一緒になつて環を形成していても良く、 R 3 represents hydrogen, d-alkyl, halogen, nitro, formyl, or acyl; R 2 and R 3 may be taken together to form a ring;
X, Yは各々独立して水素、 Ci—e アルキル、 C3-7 シクロアルキル、 C2-e ァ ルケニル、 C ハロアルキル、 C 2-6 アルキニル、 ハロゲン、 ニトロ、 ァミ ノ、 C アルキルァミ ノ、 ァシルァミ ノ、 Ci-6 アルキルスルホニルァミ ノ、 ホル ミル、 ァシル、 シァノ、 カルボキシル、'ィ ミ ノ、 ヒ ドロキシル、 Ci - 6 アルコキ シカルボニル、 C!- アルコキシ、 置換されても良いベンジルォキシ、 C2- 6 ァ ルケニルォキシ、 d ハロアルコキシ、 C2-6 アルキニルォキシ、 置換されて も良いフエノキシ、 置換されても良いベンジル、 アミ ノォキシ、 Ci-B アルキル チォ、 置換されても良いフヱニル、 Ci- アルキルスルホニル、 置換されても良 いフヱニルチオ、 C2- アルケニルチオ、 C2-6 アルキニルチオ、 置換されても 良いベンゾィル、 置換されても良いフヱニルスルホニル、 置換されても良いへテ 口環一ォキシおよびへテロ環—チォ基を表し、 又、 2つの Xもしく は 2つの Yで炭素環、 又は複素環を形成してもよく、 m , nは 1 ~ 4の整数を表す。 〕 で表される複素環誘導体もしく はそめ塩、 こ れを製造す 方法およびこれを含有する除草剤である。 X, Y are each independently hydrogen, CI- e alkyl, C 3 - 7 cycloalkyl, C 2 - e § alkenyl, C haloalkyl, C 2 - 6 alkynyl, halogen, nitro, § Mi Roh, C Arukiruami Bruno, Ashiruami Bruno, CI- 6 alkylsulfonyl § Mi Bruno, formyl, Ashiru, Shiano, carboxyl, 'I Mi Bruno, human Dorokishiru, Ci - 6 an alkoxy carbonyl, C -! alkoxy, which may be substituted Benjiruokishi, C 2 - 6 § Rukeniruokishi, d haloalkoxy, C 2 - 6 Arukiniruokishi, which may be substituted phenoxy, an optionally substituted benzyl, amino Nookishi, CI- B alkyl Chio, which may be substituted Fuweniru, CI- alkyl sulfonyl, optionally substituted good Fuweniruchio, C 2 - alkenylthio, C 2 - 6 alkynylthio, an optionally substituted Benzoiru, substituted Phenylsulfonyl, heterocyclic monooxy and heterocyclic-thio groups which may be substituted, Further, two Xs or two Ys may form a carbocyclic or heterocyclic ring, and m and n represent an integer of 1 to 4. And a method for producing the same and a herbicide containing the same.
Qの窒素、 酸素もしく は硫黄を 1 〜 4個含む 5 ~ 6員の複素環としては、 例え ば、 イ ミダゾール、 イソォキサゾール、 ォキサゾール、 ォキサジァゾール、 ピロ ール、 ピラゾール、 チアゾ一ル、 チアジアゾール、 テ トラゾ一ル、 卜 リアブール, ジチアゾール、 ピリ ミ ジン、 ピリ ジン、 ピラジン、 ォキサジン、 ピリダジン、 ピ ロン、 ト リアジン、 これらのヘテロ環のジヒ ドロ体等である。  Examples of the 5- to 6-membered heterocyclic ring containing 1 to 4 nitrogen, oxygen, or sulfur of Q include, for example, imidazole, isoxazole, oxazole, oxaziazole, pyrrol, pyrazole, thiazol, thiadiazole, and tereazole. Examples include tolazole, triaryl, dithiazole, pyrimidine, pyridine, pyrazine, oxazine, pyridazine, pyrone, triazine, and dihydro forms of these heterocycles.
さらに具体的には Q— Y nは、  More specifically, Q—Y n
Y2  Y2
Y Y
Y】 Y]
Figure imgf000005_0001
Figure imgf000006_0001
または
Figure imgf000005_0001
Figure imgf000006_0001
Or
〔式中、 Y, 〜Υ55は水素、 d アルキル、 C 3—7 シクロアルキル、 C2一 6 アルケニル、 6 ハロアルキル、 C2_6 アルキニル、 ハロゲン、 ニ トロ、 アミ ノ、 アルキルァミ ノ、 ァシルァミ ノ、 d アルキルスルホニルァミ ノ、 ホルミル、 ァシル、 シァノ、 カルボキシル、 ィ ミ ノ、 ヒ ドロキシル、 C i-6 アル コキシカルボニル、 C アルコキシ、 置換されても良いベンジルォキシ、 C2-6 アルケニルォキシ、 C i ハロアルコキシ、 C2- アルキニルォキシ、 置換され ても良いフヱノキシ、 置換されても良いベンジル、 アミ ノォキシ、 C卜6 アルキ ルチオ、 置換されても良いフヱニル、 アルキルスルホニル、 置換されても 良いフヱニルチオ、 c2_6 アルケニルチオ、 c2_6 アルキニルチオ、 置換されて も良いベンゾィル、 置換されても良いフヱニルスルホニル、 又は置換されても良 いへテロ環—ォキシおよびへテロ環一チォ基を表し、 Wherein, Y, ~Υ 55 is hydrogen, d-alkyl, C 3 - 7 cycloalkyl, C 2 one 6 alkenyl, haloalkyl, C 2 _ 6 alkynyl, halogen, two Toro, amino, Arukiruami Bruno, Ashiruami Bruno , d alkylsulfonyl § Mi Bruno, formyl, Ashiru, Shiano, carboxyl, I Mi Bruno, human Dorokishiru, C i-6 alkoxide aryloxycarbonyl, C alkoxy, which may be substituted Benjiruokishi, C 2 - 6 Arukeniruokishi, C i haloalkoxy, C 2 -alkynyloxy, optionally substituted phenoxy, optionally substituted benzyl, aminoxy, C 6 alkylthio, optionally substituted phenyl, alkylsulfonyl, optionally substituted Fuweniruchio, c 2 _ 6 alkenylthio, c 2 _ 6 alkynylthio, an optionally substituted Benzoiru, which may be substituted off Nirusuruhoniru, or substituted hetero ring to have good - Okishi and to represent heterocyclic one Chio group,
又、 2つの Υ, 〜Y55で炭素環、 又は複素環を形成してもよい。 〕 等である。 そして、 好ましく は、 Q— Υη は、
Figure imgf000006_0002
Further, two Υ, to Y 55 may form a carbocyclic or heterocyclic ring. ] And so on. And, preferably, Q-Upsilon eta,
Figure imgf000006_0002
〔式中、 二 77 は単結合または二重結合を表し、 [In the formula, 2 77 represents a single bond or a double bond;
D , が Nの時は、 D2 は NY又は 0を表し、 When D, is N, D 2 represents NY or 0,
D , が NYの時は、 D2 は CYを表し、 When D, is NY, D 2 represents CY,
D！ が 0の時は、 D2 は Nを表し、 D! When is 0, D 2 represents N,
Y及び nは前記と同じ意味を表す。 〕 である。  Y and n have the same meaning as described above. ].
これらのうち、 Qとしては、 ォキサゾール _ 5—ィル又は 2 —ォキサゾリ ン— 5—ィル基が特に好ましい。 前記 X， Y中のベンジルォキシ、 フエノキシ、 ベンジル、 フエニル、 フエニル チォ、 ベンゾィル、 フヱニルスルホニル、 ヘテロ環—ォキシ、 ヘテロ環一チォ基 を置換する基としては、 d-e アルコキシ、 C, -s アルキル、 ハロゲン、 ニトロAmong them, Q is particularly preferably an oxazole-5-yl or 2-oxazoline-5-yl group. In the above X and Y, benzyloxy, phenoxy, benzyl, phenyl, phenylthio, benzoyl, phenylsulfonyl, heterocyclic-oxy, and heterocyclic monothio groups may be substituted by de alkoxy, C, -s alkyl, Halogen, nitro
、 C 1-6 アルキルチオ、 C!— 6 アルキルスルホニル、 d-S ハロアルキル、 シァ ノ、 フエニル、 ァミ ノ、 d—s アルキルァミ ノ、 ジ一 アルキルァミ ノ、 カル バモィル、 6 アルコキシカルボニル等が挙げられ、 また 2つの置換基で環を形成 してもよい。 , C 1-6 alkylthio, C -! 6 alkylsulfonyl, dS haloalkyl, Xia Roh, phenyl, § Mi Bruno, d-s Arukiruami Bruno, di one Arukiruami Bruno, Cal Bamoiru, include 6 alkoxycarbonyl, etc., and 2 Two substituents may form a ring.
本発明の化合物は、 次の方法によって製造することが出来る。  The compound of the present invention can be produced by the following method.
(製造法一 1 )  (Manufacturing method 1)
Figure imgf000007_0001
Figure imgf000007_0001
一般式 〔2〕 （式中、 , R2 Aは前記と同じ意味を表し、 Lはハロゲン、 アルキルスルホニル基、 ァリールスルホニル基等の脱離基を表す。 ） の化合物と、 一般式 〔3〕 （式中、 B, Q, X, Y, m, nは前記と同じ意味を表す。 ） の化 合物を、 有機溶媒中で塩基の存在下カツプリ ングさせる。 塩基としては、 水素化 ナ ト リ ゥム等の水素化金属類、 炭酸力リゥム等の炭酸塩類、 卜 リェチルァミ ン等 の有機塩基類などであり、 溶媒としては、 DMF, DMS 0, THF， DME等 が挙げられる。 反応混合物は反応が完了するまで、 0~9 0°C、 場合によってはGeneral formula [2] (wherein,, R 2 A are as defined above, L is a halogen, an alkylsulfonyl group, a leaving group such as § reel sulfonyl group.) With a compound of the general formula [3 (Wherein, B, Q, X, Y, m and n have the same meanings as described above). The compound is coupled in an organic solvent in the presence of a base. Examples of the base include metal hydrides such as hydrogenated sodium, carbonates such as carbonated lime, and organic bases such as triethylamine. Solvents include DMF, DMS 0, THF, and DME. And the like. The reaction mixture is allowed to react at 0-90 ° C,
1 2 0でで撹拌される。 Stir at 120.
上記の反応における原料の 0—ヘテロ環置換フヱノール （あるいは、 ヒ ドロキ シピリ ジン） 誘導体 〔3〕 は以下に述べるような方法により製造することができ る。 尚、 特に指定をしていない場合に於いては以下の反応で用いられる溶媒とし ては、 メタノール、 エタノール、 イソプロピルアルコール等のアルコール類、 ベ ンゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホルム等のハ ロゲン化炭化水素類、 ジェチルエーテル、 THF等のエーテル類、 アセ トン、 M E K等のケ トン類、 酢酸メチル、 酢酸ェチル等のエステル類、 DMF, DMS 0 等の非プロ トン性極性溶媒、 ァセ トニト リル等の二ト リル類、 水等が挙げられる c 又、 用いられる塩基としては、 炭酸ナトリ ゥム、 炭酸力リ ゥム等の炭酸塩類、 水 酸化ナ ト リウム、 水酸化力リゥム等の水酸化金属類、 ナト リウムメチラー ト、 ナ ト リゥムェチラ一 ト等の金属アルコラ一ト類、 水素化ナト リゥム等の水素化金属 類、 ブチルリチウム等のアルキル金属類、 リチウムジイソプロピルアミ ド、 リチ ゥムビス 卜 リメチルシリルァミ ド等のリチウムアミ ド類、 ト リェチルァミ ン、 D B U等の有機塩基類等が挙げられる。 又、 用いられる酸としては塩酸、 硝酸、 硫 酸等の鉱酸類、 蟻酸、 酢酸等の有機酸類、 塩化アルミニウム、 ボロント リフロリ ドジェチルエーテル等のルイス酸類などが挙げられる。 又、 反応温度としては、 一 9 0 °C〜溶媒の沸点以下の温度が挙げられる。 （以下、 式中 X, m, Bは前記 と同じ意味を表す。 ） The 0-heterocyclic-substituted phenol (or hydroxypyridin) derivative [3] as a raw material in the above reaction can be produced by the method described below. Unless otherwise specified, solvents used in the following reactions include alcohols such as methanol, ethanol, and isopropyl alcohol, aromatic hydrocarbons such as benzene and toluene, dichloromethane, and chloroform. C such as mouth holm Hydrogenated hydrocarbons, ethers such as getyl ether and THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, non-protonic polar solvents such as DMF and DMS 0, Examples include nitriles such as cetonitrile, water and the like.c. Examples of the base used include sodium carbonate, carbonate such as carbonated carbonate, sodium hydroxide, hydroxylated phosphate and the like. Metal hydroxides such as sodium hydroxide, sodium methylate, sodium methylate, etc., metal hydrides such as sodium hydride, alkyl metals such as butyl lithium, lithium diisopropylamide, lithium bismuth Examples thereof include lithium amides such as rimethylsilylamide, and organic bases such as triethylamine and DBU. Examples of the acid to be used include mineral acids such as hydrochloric acid, nitric acid, and sulfuric acid, organic acids such as formic acid and acetic acid, and Lewis acids such as aluminum chloride and boronant fluoridated getyl ether. The reaction temperature may be from 190 ° C. to the boiling point of the solvent or lower. (Hereinafter, X, m, and B represent the same meaning as described above.)
Figure imgf000008_0001
Figure imgf000008_0001
〔3c〕  (3c)
Qがィ ミ ダゾリ ン一 2—ィルの化合物 〔 3 a〕 とイ ミダゾールー 2—ィルの化 合物 〔3 b, c〕 は、 J. Ame r. C h em. S o c. 9 6巻、 2 4 6 3ぺ一 ジ （ 1 9 7 4年） に記載の方法を応用して製造することができる。 （式中、 L , はアルコキシ、 C I , 1 _イ ミダゾ一ル基を表し、 R4 はアルキル、 ベンジル、 p— トルェンスルホニル基 （To s ) を表す。 ）
Figure imgf000009_0001
The compound [3a] having Q as imidazolin-1-yl and the compound [3b, c] of imidazole-2-yl are described in J. Amer. Chem. Soc. 9 It can be manufactured by applying the method described in Vol. 6, 2463-page (1974). (Wherein, L, represents alkoxy, CI, 1 _ i Midazo Ichiru group, R 4 represents alkyl, benzyl, p- Torr E down sulfonyl group and (To s).)
Figure imgf000009_0001
〔3d〕  [3d]
Qがイ ミダゾールー 4—ィルの化合物 〔 3 d〕 は J. Am e r. C h e m. S o c. 8 2巻、 3 3 8 6ページ （ 1 9 6 0年） に記載の方法を応用して製造する ことができる。  The compound [3d] in which Q is imidazole-4-yl is obtained by the method described in J. Amer. Chem. Soc. 82, pp. 33686 (1966). It can be manufactured by applying.
Figure imgf000009_0002
Figure imgf000009_0002
あるいは、 Qがイ ミ ダゾール— 4一ィルの化合物は、 ィ ミ ン 〔 7〕 と T o s M I C (p - トルエンスルホニルメチルイソシァニド） を、 塩基の存在下反応させ ることにより製造することができる。 詳細は、 J . O r g. C h e m. 4 2巻、 1 1 5 3ページ （ 1 9 7 7年） に記載されている。 （式中、 R4 は前記と同じ意 味を表す。 ） :Alkyl, Aryl, CF3 Alternatively, a compound in which Q is imidazole-41-yl can be produced by reacting imine [7] with Tos MIC (p-toluenesulfonylmethyl isocyanide) in the presence of a base. Can be. The details are described in J. Org. Chem. 42, Vol. 42, page 1153 (1977). (In the formula, R 4 has the same meaning as described above.) : Alkyl, Aryl, CF 3
Figure imgf000010_0001
Figure imgf000010_0001
〔 8〕 〔3f〕  [8] [3f]
Qが 1 , 3 , 4— 卜リアゾール _ 2—ィルの化合物 〔 3 f 〕 は、 化合物 〔 8〕 を酸クロライ ドもしく は、 酸無水物と DM F中、 0〜 1 2 0 °Cで反応させること により製造することができる。 （式中 R 5 はアルキル、 ァリール、 C F3 基を表 す。 ） The compound [3f] in which Q is 1,3,4-triazol_2-2-yl is obtained by converting the compound [8] to acid chloride or an acid anhydride in DMF at 0 to 120 ° C. It can be produced by reacting with. (In the formula, R 5 represents an alkyl, aryl or CF 3 group.)
Figure imgf000010_0002
Figure imgf000010_0002
Re :Alkyl,CH2Ph, Ph NaOR- L2=Halogen R e: Alkyl, CH 2 Ph, Ph NaOR- L 2 = Halogen
or Nitro  or Nitro
R7 R 7
〔11〕
Figure imgf000010_0003
[11]
Figure imgf000010_0003
3位置換— 1 , 3 , 4 _ ト リァゾールー 2 —ィル誘導体 〔 3 g〕 は J. 0 r g. C h e m. 4 4巻、 4 1 6 0ページ （ 1 9 7 9年） の教えに従い、 アミ ド 〔 9〕 とジメチルホルムアミ ド、 ジメチルァセタールを反応させて、 N— 〔 （ジメチル ァミ ノ） メチレン〕 アミ ド 〔 1 0〕 を合成する。 〔 1 0〕 にヒ ドラジン類を反応 させて、 ト リァゾール 〔 1 1〕 へと誘導する。 L2 がメ トキシメ トキシ、 ベンジ ルォキシ基の場合は、 〔 1 1〕 を酸で処理するか、 パラジウム炭素等を触媒にし た加水素化分解反応によって 〔3 g〕 が得られる。 3-position substitution-1,3,4_triazole-2-yl derivative [3g] is the teaching of J. 0rg. Chem. 4 Volume 4, 4160 pages (1977) Then, the amide [9] is reacted with dimethylformamide and dimethylacetal to synthesize N-[(dimethylamino) methylene] amide [10]. Hydrazines react with [10] To induce Triazole [11]. When L 2 is a methoxymethoxy or benzyloxy group, [11] is treated with an acid, or [3 g] is obtained by a hydrogenolysis reaction using palladium carbon or the like as a catalyst.
L 2 がハロゲン、 ニ トロの場合には、 〔 1 1〕 にナ ト リ ウムアルコラ一トを反 応させて、 化合物 〔 1 2〕 を合成する。 〔 1 2〕 から 〔3 g〕 への変換は、 " P r o t e c t i v e G r o u p s i n O r g a n i c S y n t h e s i s " T. W. G r e e n e編集、 J OHN WI LEY & SONS, N. Y, 発行、 第 3章 8 7ページに記載の方法から、 適切な反応を選択して行われるが、 例えば、 1 ) L i C 1等の塩を DMFや DMS 0等の溶媒中で、 加熱する方法。 2 ) H B r 酢酸中加熱する方法。 3) ピリ ジン塩酸塩中加熱する方法。 4 ) 金 属触媒を用いた加水素化分解による方法。 5) ボロン ト リハライ ド等のルイス酸 による脱アルキル化等が挙げられる。 （式中 L2 はメ トキシメ 卜キシ、 ベンジル ォキシ、 ニ トロ基、 ハロゲンを表し、 Re はアルキル、 ベンジル、 フエ二ル基を 表し、 R7 はアルキル、 ベンジル基を表す。 ） When L 2 is halogen or nitrogen, compound [12] is synthesized by reacting [11] with sodium alcoholate. Conversion from [1 2] to [3g] is described in Chapter 3, pages 87, edited by "Protective Group Organic Synthesis", edited by TW Greene, published by JOHN WI LEY & SONS, NY, NY. The reaction is carried out by selecting an appropriate reaction from the above methods. For example, 1) a method in which a salt such as LiC1 is heated in a solvent such as DMF or DMS0. 2) Heating in HBr acetic acid. 3) Heating in pyridine hydrochloride. 4) Hydrogenolysis using a metal catalyst. 5) Dealkylation with a Lewis acid such as boron trihalide. (Wherein L 2 represents main Tokishime Bok alkoxy, benzyl Okishi, nitro group, halogen, R e represents alkyl, benzyl, phenylene Le group, R 7 represents alkyl, a benzyl group.)
Figure imgf000011_0001
Figure imgf000011_0001
Qがテトラゾールー 5—ィルの誘導体は、 J. Ame r. Ch em. S o c. 8 0巻、 3 9 0 8ページ （ 1 9 5 8年） の方法を応用して、 二ト リル 〔 1 3〕 に アジ化ナ ト リゥムと塩化アンモニゥムを DMF中 8 0~ 1 4 0°Cで 1〜4 8時間 反応させることにより製造できる。 SnMe Derivatives in which Q is tetrazol-5-yl can be obtained by applying the method described in J. Amer. Chem. Soc., Vol. 80, pp. 398 (1958). [13] can be produced by reacting sodium azide and ammonium chloride in DMF at 80 to 140 ° C for 1 to 48 hours. SnMe
Figure imgf000012_0001
Figure imgf000012_0001
〔3 h〕 は J. O r g. C h em. 5 6巻、 2 3 9 5ページ （ 1 9 9 1年） に 記載されている方法により、 スズアジ ドと 〔 1 3〕 を反応させても製造すること ができる。 [3h] is obtained by reacting tin azide with [13] according to the method described in J. Org. Chem. 56, pp. 2395 (1991). Can also be manufactured.
Figure imgf000013_0001
Figure imgf000013_0001
〔15〕 〔16〕 〔17〕  (15) (16) (17)
R8 :Alkyl，Aryl，CF3 NaOR7 L2=Halogen R 8: Alkyl, Aryl, CF 3 NaOR 7 L 2 = Halogen
or Nitro R9:H, Alkyl, COOR,0 or Nitro R 9 : H, Alkyl, COOR, 0
Ri  Ri
〔17〕
Figure imgf000013_0002
[17]
Figure imgf000013_0002
〔3i〕  [3i]
Qがチアゾ一ル— 2—ィルの誘導体は以下のようにして合成される。 チオアミ ド 〔 1 5〕 とプロモケ ト ン 〔 1 6〕 をアルコール中 2 5〜8 0 °Cで、 1〜2 0時 間反応させて 〔 1 7〕 を合成する。 次いで 〔 1 7〕 から 〔3 g〕 の製造法と同様 の反応を行うことによって 〔3 i〕 が製造される。 （式中、 R8 はアルキル、 Ύ リール、 C F3 基を表し、 Rg は水素、 アルキル、 C OOR10基を表し、 R10は アルキル基を表し、 L 2 , RT は前記と同じ意味を表す。 ） A derivative in which Q is thiazol-2-yl is synthesized as follows. The thioamide [15] and the promotone [16] are reacted in an alcohol at 25 to 80 ° C for 1 to 20 hours to synthesize [17]. Next, [3i] is produced by performing the same reaction as in the production method of [17] to [3g]. (Wherein, R 8 represents alkyl, 、 reel, CF 3 group, R g represents hydrogen, alkyl, COOR 10 group, R 10 represents alkyl group, and L 2 and RT have the same meanings as above. Represents.)
Figure imgf000014_0001
Figure imgf000014_0001
： H, Alkyl, C00R10 NaOR7 L2=Halogen ： H, Alkyl, C00R 10 NaOR 7 L 2 = Halogen
or Nitro  or Nitro
： Alkyl, Aryl,RI 3NH : Alkyl, Aryl, R I 3 NH
〔20〕
Figure imgf000014_0002
[20]
Figure imgf000014_0002
〔3j〕  [3j]
Qがチアゾール— 4 —ィルの誘導体 〔 3 j〕 は、 〔 1 9〕 とプロモケ トン 〔 1 8〕 をアルコール中 2 5〜 8 0 で、 1〜 2 0時間反応させてチアゾ一ル環を形 成した後に、 〔 3 g〕 の製造法と同様の反応を行うことにより製造される。  The derivative [3j] of Q is thiazole-4-yl is obtained by reacting [19] with the promotone [18] in an alcohol at 25 to 80 for 1 to 20 hours to form a thiazole ring. After being formed, it is produced by performing the same reaction as in the production method of [3 g].
(式中、 は水素、 アルキル、 C OOR!。基を表し、 R12はアルキル、 ァリ一 ル、 R13NH基を表し、 R13は水素、 アルキル、 ァリール基を表し、 L2 , R7 ， R10は前記と同じ意味を表す。 ） (Wherein, represents hydrogen, alkyl, COOR !. group, R 12 represents alkyl, aryl, R 13 NH group, R 13 represents hydrogen, alkyl, aryl group, L 2 , R 7 and R 10 represent the same meaning as described above.
Figure imgf000015_0001
Figure imgf000015_0001
〔21〕 〔19〕 〔22〕  (21) (19) (22)
R14 R 14
〔22〕
Figure imgf000015_0002
〔twenty two〕
Figure imgf000015_0002
〔3k〕  [3k]
Qがチアゾールー 5—ィルの誘導体 〔 3 k〕 も、 前述と同様の方法によって製 造することが出来る。 （式中 R14は水素、 アルキル基を表し、 L2 ， R7 , R12 は前記と同じ意味を表す。 ） The derivative [3k] of thiazol-5-yl for Q can also be produced by the same method as described above. (In the formula, R 14 represents hydrogen or an alkyl group, and L 2 , R 7 , and R 12 represent the same meaning as described above.)
尚、 これらのチアゾール誘導体 〔3 i〜k〕 の合成法は、 C h e m. H e t e r o c y c l i c. C omp o u n d s, 3 4卷、 パー ト 1〜3 ( 1 9 7 8 ~ 1 9 7 9年） 、 あるいは、 "H e t e r o c y c l i c C omp o u n d s " R. C. E 1 d e r f i e 1 d編集、 W I LEY. N. Y. 発行、 5巻、 4 8 4〜 7 2 2ページ （ 1 9 5 7年） に記載されている。
Figure imgf000016_0001
The method for synthesizing these thiazole derivatives [3 i to k] is described in Chem. Heterocyclic c. Comounds, 34 volumes, parts 1 to 3 (1978 to 1979). Or "Heterocyclic Compounds" edited by RC E1 derfie 1d, published by WI LEY. NY, vol. 5, pages 484-7272 (1957).
Figure imgf000016_0001
〔 9〕 〔23〕  [9] [23]
Ri 5 ： H, Alkyl.Ph, CF3 L2=Halogen Ri 5: H, Alkyl.Ph, CF 3 L 2 = Halogen
or Ni tro  or Ni tro
R16 R 16
〔24〕
Figure imgf000016_0002
〔twenty four〕
Figure imgf000016_0002
〔31〕  [31]
Qがォキサゾール— 2—ィルの誘導体 〔 3 1〕 はアミ ド 〔 9〕 とプロモケ トン 〔 2 3〕 を 5 0~ 1 6 0 °Cで 1 ~4 8時間反応させて 〔 2 4〕 とした後に 〔 3 g〕 の製造法と同様の反応を行うことにより製造することが出来る。 （式中、 R15は 水素、 アルキル、 フエニル、 C F3 基を表し、 R16は水素、 アルキル、 フエニル 基を表し、 L2 ， R7 は前記と同じ意味を表す。 ） The derivative [31] of Q is oxazole-2-yl is obtained by reacting the amide [9] with the promoketone [23] at 50 to 160 ° C for 1 to 48 hours with [24]. After that, the reaction can be carried out in the same manner as in the production method of [3 g]. (In the formula, R 15 represents a hydrogen, alkyl, phenyl or CF 3 group, R 16 represents a hydrogen, an alkyl or phenyl group, and L 2 and R 7 have the same meanings as described above.)
+ ヽ, + ヽ,
L2=HalogenL 2 = Halogen
Figure imgf000016_0003
or Nitro Xm
Figure imgf000016_0003
or Nitro Xm
〔 9〕 〔25〕  (9) (25)
Figure imgf000016_0004
Figure imgf000016_0004
〔26〕 〔3m〕 〔 9〕 とビニレンカルボネー トとの反応により化合物 〔 2 5〕 を合成し、 〔 2 6〕 を経て 〔 3 g〕 の製造法と同様の反応を行うことにより、 〔 3 m〕 が得られ る。 （式中、 L2 ， R7 は前記と同じ意味を表す。 ） (26) (3m) Compound (25) is synthesized by reacting (9) with vinylene carbonate, and (3m) is obtained by performing the same reaction as in the production method of (3 g) via (26). You. (In the formula, L 2 and R 7 represent the same meaning as described above.)
Figure imgf000017_0001
Figure imgf000017_0001
〔3n〕  [3n]
Qがォキサゾールー 4 _ィルの誘導体も 〔 3 1〕 と同様の反応により得られる c 化合物 〔 2 7〕 とアミ ド 〔 2 8〕 を 5 0~ 1 6 0 °Cで 1 ~4 8時間反応させてォ キサゾール誘導体 〔 2 9〕 を得た後、 〔 2 9〕 より 〔 3 g〕 の製造法と同様の反 応を行うことにより 〔 3 n〕 を製造することが出来る。 （式中、 L3 はハロゲン を表し、 R17は水素、 メチル、 ェチル基、 C OOR10を表し、 R18は水素、 アル キル、 フ 二ル基を表し、 L2 、 R7 , R10は前記と同じ意味を表す。 ） Derivative of oxazole-4-yl is also obtained by the same reaction as (31) .c Compound (27) and amide (28) are reacted at 50 to 160 ° C for 1 to 48 hours. After obtaining the oxazole derivative [29], [3n] can be produced by performing the same reaction as in the production method of [3g] from [29]. (Wherein L 3 represents halogen, R 17 represents hydrogen, methyl, ethyl group, COOR 10 ; R 18 represents hydrogen, alkyl, phenyl group; L 2 , R 7 , R 10 Represents the same meaning as described above.
Figure imgf000018_0001
Figure imgf000018_0001
〔21〕 〔28〕 〔30〕  (21) (28) (30)
NaOR7 L2=Halogen NaOR 7 L 2 = Halogen
or Nitro  or Nitro
〔30〕
Figure imgf000018_0002
[30]
Figure imgf000018_0002
〔3o〕  [3o]
Qがォキサゾールー 5—ィルの誘導体 〔3 o〕 は、 プロモケ トン 〔2 1〕 とァ ミ ド 〔2 8〕 より得られる 〔3 0〕 を 〔 3 g〕 の製造法と同様の反応を行うこと により、 製造される。 （式中、 L2 , R7 ， R14， R18は前記と同じ意味を表す。） Derivative [3o] of oxazole-5-yl Q reacts [30] obtained from promoketone [21] and amide [28] in the same manner as [3g]. It is manufactured by doing so. (In the formula, L 2 , R 7 , R 14 , and R 18 represent the same meaning as described above.)
〔33〕
Figure imgf000018_0003
(33)
Figure imgf000018_0003
酸クロリ ド 〔 3 1〕 をジァゾケ トン 〔3 2〕 に誘導した後に、 適当なルイス酸 の存在下、 二ト リル類と反応させることにより、 ォキサゾール— 5—ィル誘導体 〔3 3〕 が得られる。 〔3 3〕 から 〔 3 p〕 への変換は 〔 3 g] の製造法と同様 の反応を行うことにより達成される。 （式中、 R19はアルキル、 フヱニル基を表 し、 L2 , R7 は前記と同じ意味を表す。 ） After derivatization of the acid chloride [31] to diazoketone [32], a suitable Lewis acid The oxazole-5-yl derivative [33] is obtained by reacting with a nitrile in the presence of. The conversion from [33] to [3p] is achieved by performing the same reaction as in the production method of [3g]. (In the formula, R 19 represents an alkyl or phenyl group, and L 2 and R 7 represent the same meaning as described above.)
Figure imgf000019_0001
Figure imgf000019_0001
化合物 〔3 4〕 とイソ二 卜 リル類 〔3 5〕 を、 ブチルリチウムや水素化ナ ト リ ゥム等の塩基の存在下、 — 7 8~8 0°Cで 0. 5〜2 4時間反応させることによ り、 化合物 〔3 6〕 を得る。 〔3 6〕 を 〔 3 g〕 の製造法と同様の反応を行うこ とにより、 〔 3 Q〕 を製造することができる。 （式中、 R2。は水素、 アルキル、 ベンジル、 フヱニル基、 COOR21， To s、 リ ン酸エステル基を表し、 R21は アルキル基を表し、 , L2 , R7 は前記と同じ意味を表す。 ） Compound [34] and isonitriles [35] are treated in the presence of a base such as butyllithium or sodium hydride at —78 to 80 ° C for 0.5 to 24 hours. By reacting, the compound [36] is obtained. [3Q] can be produced by subjecting [36] to the same reaction as in the production method of [3g]. (Wherein, R 2 represents hydrogen, alkyl, benzyl, phenyl, COOR 21 , Tos, a phosphate group, R 21 represents an alkyl group,, L 2 and R 7 have the same meanings as described above. Represents.)
Figure imgf000020_0001
Figure imgf000020_0001
NaORv L2=Halogen NaORv L 2 = Halogen
R22 ： H, Alkyl, CH2Ph or Nitro R 22 : H, Alkyl, CH 2 Ph or Nitro
〔39〕
Figure imgf000020_0002
(39)
Figure imgf000020_0002
〔3r〕  (3r)
Qがォキサゾールー 5—ィルの誘導体 〔3 r〕 は次の方法によっても製造され る。 即ち、 アルデヒ ド 〔3 7〕 にイソ二トリル 〔3 8〕 を炭酸力リゥムゃ水素化 ナトリウム等の塩基の存在下、 2 5〜 1 0 0 で0. 5 ~ 8時間反応させること で 〔3 9〕 を得た後、 〔 3 g〕 の製造法と同様の反応を行う方法である。 （式中、 R22は水素、 アルキル、 ベンジル基を表し、 L2 , R7 は前記と同じ意味を表す。） The derivative [3r] of Q is oxazole-5-yl can also be produced by the following method. That is, by reacting isonitrile [38] with aldehyde [37] in the presence of a base such as sodium carbonate hydride at 25 to 100 for 0.5 to 8 hours. [9], followed by the same reaction as in [3 g]. (In the formula, R 22 represents a hydrogen, an alkyl, or a benzyl group, and L 2 and R 7 represent the same meaning as described above.)
〔40〕 〔41〕 (40) (41)
R23 ： H, Alkyl, Halogen R 23: H, Alkyl, Halogen
〔42〕 (42)
Figure imgf000021_0001
Figure imgf000021_0001
Qが縮合ォキサゾールー 2—ィルの誘導体 〔 3 s〕 は化合物 〔4 0〕 に了ミ ノ フエノール 〔4 1〕 を反応させることにより、 化合物 〔4 2〕 を経て、 〔3 g] の製造法と同様の反応を行うことにより、 製造される。 （式中、 R23は水素、 ァ ルキル基、 ハロゲンを表し、 L2 ， R7 は前記と同じ意味を表す。 ） The derivative [3s] of Q is a condensed oxazole-2-yl is prepared by reacting compound [40] with thiominophenol [41] to give compound [4 2] via compound [42]. It is produced by performing the same reaction as described above. (In the formula, R 23 represents hydrogen, an alkyl group, or halogen, and L 2 and R 7 have the same meanings as described above.)
尚、 ォキサゾール誘導体 〔3 l ~s〕 の製造法に関する著書としては多数ある 力く、 " H e t e r o c y c l i c C omp o u n d s " 4 5卷、 I . J. T u r c h i編集、 JOHN W I LEY, N. Y. 発行 （ 1 9 8 6年） 及び、 " H e t e r o c y c l i c C omp o un d s " R. C . E l d e r f i e l d 編集、 WI L EY. N. Y. 発行、 5卷、 2 9 8 ~ 4 5 1頁 （ 1 9 57年） に記 載の方法、 文献を参考にすることができる。 In addition, there are many books on the production method of the oxazole derivative [3l to s], which are published in “Heterocyclic Compounds”, Vol. 45, edited by I. J. Turchi, published by John Wiley, NY (19 86 years) and "Heterocyclic Composites" edited by R. C. Elderfield, published by WI EY. NY, Vol. 5, pp. 298-451 (1957). And the literature can be referred to.
Figure imgf000022_0001
Figure imgf000022_0001
Figure imgf000022_0002
Figure imgf000022_0002
〔3v〕  [3v]
化合物 〔4 3〕 とヒ ドロキシルァミ ンをエタノール中、 5 0 ~ 7 0 で 0. 5 〜 8時.間反応させることでィソォキサゾール一 3—ィル体 〔 3 t〕 とィソォキサ ゾリ ン— 5—ィル体 〔 3 u〕 の混合物が得られる。 〔3 t〕 と 〔3 u〕 はクロマ トグラフィーゃ再結晶により、 容易に分離できる。 〔3 t〕 と 〔3 u〕 と各々 D D Q等の酸化剤によって酸化することで、 イソォキサゾ一ル— 3—ィル体 〔3 v〕 及び、 イソォキサゾ一ル— 5 _ィル体 〔3w〕 を製造することが出来る。 （式中、 R, 8, R23は前記と同じ意味を表す。 ） The compound [43] and hydroxylamine are reacted in ethanol at 50 to 70 for 0.5 to 8 hours to give the isoxazole-13-yl form [3t] and isoxoxazolin-5-y. Thus, a mixture of [3 u] is obtained. [3t] and [3u] can be easily separated by chromatography-recrystallization. By oxidizing [3t] and [3u] with an oxidizing agent such as DDQ, respectively, the isoxazole-3-yl form [3v] and the isoxazole-5-yl form [3w] are obtained. Can be manufactured. (Wherein, R, 8, R 23 are as defined above.)
Figure imgf000022_0003
Figure imgf000022_0003
〔46〕 〔3x〕 P T/JP94/00109 (46) (3x) PT / JP94 / 00109
2 1 twenty one
Qがイソォキサゾールー 4—ィルの誘導体 〔3 x〕 は、 化合物 〔4 4〕 をホル ミルイ匕して 〔4 5〕 とした後に、 ヒ ドロキシルァミ ンによって環化させ、 最後に フエノールの保護基を外すことにより製造される。 この反応の参考文献としては、 薬学雑誌、 7 9卷、 6 2 3頁 （ 1 9 5 9年） が挙げられる。 （式中、 R24は水素、 アルキル、 フニ二ル基を表す。 ) Derivative [3x] of Q isoxazole-4-yl is obtained by converting compound [44] into formylolate to form [45], cyclizing with hydroxylamine, and finally phenol. It is produced by removing the protecting group. References for this reaction include Pharmaceutical Journal, Vol. 79, p. 623 (1959). (In the formula, R 24 represents a hydrogen, alkyl, or funinyl group.)
Figure imgf000023_0001
Figure imgf000023_0001
〔47〕 〔3y〕  (47) (3y)
あるいは、 ベンゾフラン 〔4 7〕 とヒ ドロキシルァミ ンとをアルコール中、 2 5 ~ 8 0 °Cで 0. 5〜 8時間反応させることで 〔 3 y〕 を製造することが出来る,  Alternatively, (3y) can be produced by reacting benzofuran [47] with hydroxylamine in alcohol at 25 to 80 ° C for 0.5 to 8 hours,
tro tro
Figure imgf000023_0002
Figure imgf000023_0002
〔3z〕  [3z]
1， 2, 4—ォキサジァゾール— 5—ィルの誘導体 〔 3 z〕 は、 〔3 4〕 とァ ミ ドキシム 〔4 8〕 とを塩基の存在下、 0〜 1 4 0°Cで 1〜 8時間反応させて 〔4 9〕 とした後に、 〔3 g〕 の製造法と同様の反応を行うことにより、 製造さ れる。 （式中、 R25は水素、 アルキル、 ベンジル、 ァリール、 ハロアルキル、 ァ ルコキシアルキル、 アルキルチオアルキルを表し、 ， L2 , R7 は前記と同 じ意味を表す。 ） 1,2,4-oxaziazol-5-yl derivative [3z] is obtained by converting [34] and amidoxime [48] in the presence of a base in the range of 1 to 8 at 0 to 140 ° C. After reacting for 4 hours to obtain [49], the same reaction as in the production method of [3 g] is performed, It is. (In the formula, R 25 represents hydrogen, alkyl, benzyl, aryl, haloalkyl, alkoxyalkyl, or alkylthioalkyl, and L 2 and R 7 have the same meanings as described above.)
o o
〔51〕
Figure imgf000024_0001
(51)
Figure imgf000024_0001
〔3a'〕  [3a ']
化合物 〔 50〕 と酸クロリ ドもしく は、 酸無水物との反応を行い、 〔 5 1〕 を 得た後に、 〔 3 g〕 の製造法と同様の反応を行うことにより、 1， 2， 4—ォキ サジァゾ一ル— 3—ィルの誘導体 〔3 a ' 〕 が製造される。 （式中、 L2 , R5 , R7 は前記と同じ意味を表す。 ） The compound [50] is reacted with an acid chloride or an acid anhydride to obtain [51], followed by the same reaction as in the production method of [3 g] to obtain 1, 2, and A derivative of 4-oxaziazol-3-yl [3a '] is produced. (In the formula, L 2 , R 5 and R 7 represent the same meaning as described above.)
Figure imgf000024_0002
Figure imgf000024_0002
〔47〕 〔3b'〕  (47) (3b ')
ベンゾフラン 〔 4 7〕 とヒ ドラジン類を 2 5 ~ 8 0でで 0. 5〜 8時間反応さ せることで、 ピラゾールー 4—ィルの誘導体 〔3 b' 〕 を製造することが出来る, (式中、 R6 は前記と同じ意味を表す。 ） By reacting benzofuran [47] with hydrazines at 25 to 80 for 0.5 to 8 hours, pyrazole-4-yl derivative [3 b '] can be produced. (Wherein, R 6 has the same meaning as described above.)
Figure imgf000025_0001
Figure imgf000025_0001
〔52〕 or 0CH2Ph 〔53〕 〔54〕 (52) or 0CH 2 Ph (53) (54)
R26, R27 ： CN, COOR10, Ph R26, R27 ： CN, COOR 10 , Ph
Figure imgf000025_0002
Figure imgf000025_0002
〔3c'〕  [3c ']
ピロ一ルー 3—ィルの誘導体 〔3 c ' 〕 はケ 卜ン 〔52〕 をォキシム 〔5 3〕 と した後に、 アセチレン化合物との反応で環化させて、 ピロール環を形成して 〔54〕 とした後に 〔3 g〕 の製造法と同様の反応を行うことにより、 製造され る。 （式中 R26, R27は CN, C OORio> フヱニル基を表し、 L2 , R10は前 記と同じ意味を表す。 ） The derivative of pyrrolyl-3-yl [3c '] is obtained by converting ketone [52] to oxime [53], and then cyclizing it with an acetylene compound to form a pyrrole ring. And then performing the same reaction as in the production method of [3 g]. (In the formula, R 26 and R 27 each represent a CN, COORio> phenyl group, and L 2 and R 10 have the same meaning as described above.)
Figure imgf000025_0003
Figure imgf000025_0003
〔55〕 〔3d'〕  [55] [3d ']
ケ トン 〔5 5〕 を、 グリオキシル酸とヒ ドラジンと反応させることにより、 3 一ピリダジノ ン一 6—ィルの誘導体 〔3 d' 〕 を製造することができる。  By reacting ketone [55] with glyoxylic acid and hydrazine, a derivative of 3-pyridazinone-6-yl [3d '] can be produced.
又、 次の方法によっても一般式 〔 1〕 で表される化合物は製造することが出来 る。  The compound represented by the general formula [1] can also be produced by the following method.
(製造法一 2 )
Figure imgf000026_0001
(Production method 1)
Figure imgf000026_0001
上述の、 化合物 〔3〕 の合成法に準じた方法で製造することが出来る。 即ち、 一般式 〔5 6〕 で示される化合物と、 上記 〔3〕 の製造法で示された、 適当な縮 合剤を反応させることにより 〔 1〕 を製造する方法である。  The compound can be produced by a method similar to the method for synthesizing compound [3] described above. That is, this is a method for producing [1] by reacting a compound represented by the general formula [56] with an appropriate condensing agent shown in the production method of the above [3].
但し、 置換ピリ ミジンを含有する事で問題がある場合は、 この方法は用いられ ない。 （式中、 ， R2 ， A, B, Q, X, Y, Z, m, nは前記の意味を表 し、 Rは However, if there is a problem with containing the substituted pyrimidine, this method is not used. (Where,, R 2 , A, B, Q, X, Y, Z, m, n represent the above-mentioned meanings, and R is
COL, COCHO CN CHO /NH2 S ^ /NH2 COL, COCHO CN CHO / NH 2 S ^ / NH 2
Figure imgf000026_0002
Figure imgf000026_0002
OHOH
HN. -NHNH2 HN OEt H2N OHC C00R, HN.-NHNH 2 HN OEt H 2 N OHC C00R,
128 28 29 R 28 CN, COOR10 128 28 29 R 28 CN, COOR 10
R29 ： H, Alkyl, CH2Ph, Aryl, C00RI O,Tos に示した基を表す。 L^ LS. R^. RU. R . R . R^ は前記と同じ意味を表す。 ） a ) テトラゾ一ル 〔 1 a〕 の製造法 CNR 29 : H, Alkyl, CH 2 Ph, Aryl, C00R IO , represents the group shown in Tos. L ^ LS. R ^. RU. R. R. R ^ has the same meaning as described above. A) Method for producing tetrazole [1a] CN
R,
Figure imgf000027_0001
〔la〕 R,
Figure imgf000027_0001
[La]
一般式 〔5 7〕 で示される化合物とアジ化ナ ト リゥムを適当な溶媒中、 好まし く は DMFを用い、 室温〜溶媒の沸点未満の温度、 好ましく は 8 0〜 1 2 0 で 1 - 2 4時間反応させることにより製造される。 （以下、 式中、 R, , R2 , A, B, Z, X， mは前記の意味を示す。 ） N /： i〇 The compound represented by the general formula [57] and sodium azide are mixed in a suitable solvent, preferably using DMF, at a temperature from room temperature to a temperature lower than the boiling point of the solvent, preferably 80 to 120 to 1-. Manufactured by reacting for 24 hours. (Hereinafter, in the formula, R,, R 2 , A, B, Z, X, and m have the above meanings.) N /: i〇
b) ピロール 〔 l b〕 ， 〔 l c〕 ， 〔 l d〕 の製 \造N法 b) Production of pyrrole [lb], [lc] and [ld]
Figure imgf000027_0002
一般式 〔5 8〕 、 あるいは 〔 5 9〕 で示される化合物と T 0 s M I C等のイソ シアニド類を適当な塩基の存在下、 適当な溶媒中、 室温〜溶媒の沸点未満の温度 で 1 ~ 2 4時間反応させることにより製造される。 この反応に用いられる溶媒と しては、 例えば、 メ タノール、 エタノール、 イソプロパノール等のアルコール類、 ベンゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホルム等の ハロゲン化炭化水素類、 ジェチルエーテル、 T H F等のエーテル類、 アセ ト ン、 M E K等のケ トン類、 酢酸メチル、 酢酸ェチル等のエステル類、 D M F， D M S 0等の非プロ トン性極性溶媒、 ァセ トニト リル、 水等が挙げられる。 又、 この反 応に用いられる塩基としては、 炭酸ナト リウム、 炭酸カリウム等の炭酸塩類、 水 酸化ナ ト リウム、 水酸化力リゥム等の水酸化金属類、 ナ ト リウムメチラー ト、 ナ ト リウムェチラ一 ト等の金属アルコラ一 ト類、 水素化ナト リウム、 水素化力リゥ ム等の水素化金属類、 リチウムジイソプロピルアミ ド、 リチウムビス ト リ メチル シリルァミ ド等のリチウムアミ ド類、 卜 リェチルァミ ン、 D B U等の有機塩基類 等が挙げられる。
Figure imgf000027_0002
A compound represented by the general formula [58] or [59] and an isomeric compound such as T s MIC. It is produced by reacting cyanides in the presence of a suitable base in a suitable solvent at room temperature to a temperature lower than the boiling point of the solvent for 1 to 24 hours. Examples of the solvent used for this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; Ethers such as ether, THF, etc., ketones such as acetate, MEK, etc., esters such as methyl acetate, ethyl acetate, non-protonic polar solvents such as DMF and DMS 0, acetonitrile, water, etc. No. Bases used in this reaction include carbonates such as sodium carbonate and potassium carbonate, sodium hydroxide, metal hydroxides such as hydroxylating lime, sodium methylate and sodium ethylate. Metal hydrides such as sodium hydride, hydrogen hydride, lithium amides such as lithium diisopropylamide, lithium bistrimethylsilylamide, triethylamine, DBU, etc. Organic bases and the like.
c ) イ ミ ダゾール 〔 1 e〕 の製造法 c) Method for producing imidazole [1e]
Figure imgf000028_0001
文献公知の方法に従い、 一般式 〔 6 0〕 で示される化合物と T 0 s M I Cを適 当な塩基の存在下、 適当な溶媒中、 室温〜溶媒の沸点未満の温度で 1 ~ 2 4時間 反応させることにより製造される。
Figure imgf000028_0001
According to a method known in the literature, the compound represented by the general formula (60) is reacted with T 0 s MIC in a suitable solvent in a suitable solvent at a temperature from room temperature to a temperature lower than the boiling point of the solvent for 1 to 24 hours. It is manufactured by having
この反応に用いられる溶媒としては、 例えば、 メタノール、 エタノール、 イソ プロパノール等のアルコール類、 ベンゼン、 トルエン等の芳香族炭化水素類、 ジ クロロメタン、 クロ口ホルム等のハロゲン化炭化水素類、 ジェチルエーテル、 T H F等のエーテル類、 アセ トン、 M E K等のケ トン類、 酢酸メチル.、 酢酸ェチル 109 Examples of the solvent used in this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; Ethers, ethers such as THF, ketones such as acetone, MEK, methyl acetate., Ethyl acetate 109
2 7 等のエステル類、 DMF, DMS 0等の非プロ トン性極性溶媒、 ァセ トニト リル- 水等が挙げられる。 又、 この反応に用いられる塩基としては、 炭酸ナ ト リ ウム、 炭酸力リゥム等の炭酸塩類、 水酸化ナ ト リウム、 水酸化力リゥム等の水酸化金属 類、 ナ ト リ ウムメチラー ト、 ナ ト リ ウムェチラー ト等の金属アルコラ一ト類、 水 素化ナ ト リウム、 水素化カリ ウム等の水素化金属類、 リチウムジイソプロピルァ ミ ド、 リチウムビス ト リメチルシリルアミ ド等のリチウムアミ ド類、 ト リェチル ァミ ン、 DBU等の有機塩基類等が挙げられる。 Esters such as 27, non-protonic polar solvents such as DMF and DMS 0, and acetonitrile-water. Examples of the base used in this reaction include sodium carbonate, carbonate such as sodium carbonate, sodium hydroxide, metal hydroxide such as sodium hydroxide, sodium methylate, and sodium hydroxide. Metal alcohols such as lithium ethylate; metal hydrides such as sodium hydride and potassium hydride; lithium amides such as lithium diisopropylamide and lithium bistrimethylsilyl amide; Organic bases such as triethylamine and DBU are exemplified.
d) ピラゾロン 〔 1 f 〕 の製造法 d) Production method of pyrazolone [1f]
Figure imgf000029_0001
Figure imgf000029_0001
一般式 〔6 1〕 で示される化合物とヒ ドラジン類を適当な塩基の存在下、 若し く は非存在下、 適当な溶媒中、 室温〜溶媒の沸点未満の温度で 1 ~ 24時間反応 させることにより製造される。 この反応に用いられる溶媒と しては、 例えば、 メ タノ一ル、 エタノール、 イソプロパノール等のアルコール類、 ベンゼン、 トルェ ン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホルム等のハロゲン化炭化水 素類、 ジェチルエーテル、 THF等のエーテル類、 アセ トン、 MEK等のケ トン 類、 酢酸メチル、 酢酸ェチル等のエステル類、 DMF, DMSO等の非プロ トン 性極性溶媒、 ァセ トニト リル、 水等が挙げられる。 又、 この反応に用いられる塩 基としては、 炭酸ナト リウム、 炭酸力リゥム等の炭酸塩類、 水酸化ナトリウム、 水酸化力リ ゥム等の水酸化金属類、 ナト リ ウムメチラー ト、 ナ トリ ゥムェチラ一 ト等の金属アルコラ一ト類、 水素化ナ ト リウム、 水素化力リ ゥム等の水素化金属 類、 リチウムジイソプロピルアミ ド、 リチウムビス 卜 リメチルシリルアミ ド等の リチウムアミ ド類、 ト リェチルァミ ン、 D B U等の有機塩基類等が挙げられる。 The compound represented by the general formula [61] is reacted with a hydrazine in the presence or absence of a suitable base in a suitable solvent at a temperature from room temperature to a temperature lower than the boiling point of the solvent for 1 to 24 hours. It is manufactured by Examples of the solvent used in this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; and halogenated hydrocarbons such as dichloromethane and chloroform. , Ethers such as getyl ether and THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, non-protonic polar solvents such as DMF and DMSO, acetonitrile, and water And the like. Examples of the base used in this reaction include sodium carbonate, carbonate such as carbonated lime, sodium hydroxide, metal hydroxide such as hydroxylated lime, sodium methylate and sodium methacrylate. Metal hydrides such as sodium hydride, hydrogen hydride, etc .; lithium amides such as lithium diisopropylamide and lithium bistrimethylsilyl amide; and triethylamid And organic bases such as DBU.
(式中、 R6 , R 10は前記と同じ意味を表す。 ） e ) チアゾ一ル 〔 1 g〕 の製造法 (In the formula, R 6 and R 10 represent the same meaning as described above.) e) Production method of thiazole [1g]
Figure imgf000030_0001
Figure imgf000030_0001
〔62〕 〔16〕 〔lg〕  (62) (16) (lg)
一般式 〔6 2〕 で示される化合物とプロモケ トン 〔 1 6〕 を適当な塩基の存在 下、 若しく は非存在下、 適当な溶媒中、 室温〜溶媒の沸点未満の温度で 1〜 2 4 時間反応させることにより製造される。 この反応に用いられる溶媒としては、 例 えば、 メタノール、 エタノール、 イソプロパノール等のアルコール類、 ベンゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホルム等のハロゲン化 炭化水素類、 ジェチルエーテル、 THF等のエーテル類、 アセ トン、 MEK等の ケ トン類、 酢酸メチル、 酢酸ェチル等のエステル類、 DMF, DMSO等の非プ 口 トン性極性溶媒、 ァセ トニト リル等が挙げられる。 又、 この反応に用いられる 塩基と しては、 炭酸ナ ト リゥム、 炭酸力リゥム等の炭酸塩類、 水酸化ナ ト リ ゥム- 水酸化力リ ゥム等の水酸化金属類、 ナ ト リウムメチラー ト、 ナ ト リゥムェチラ一 卜等の金属アルコラ一ト類、 水素化ナトリウム、 水素化力リゥム等の水素化金属 類、 リチウムジイソプロピルアミ ド等のリチウムアミ ド類、 ト リェチルァミ ン、 D B U等の有機塩基類等が挙げられる。 （式中、 R8 . R8 は前記と同じ意味を 表す。 ） The compound represented by the general formula [62] and the promoketone [16] are reacted with a suitable base in the presence or absence of a suitable base in a suitable solvent at a temperature from room temperature to a temperature lower than the boiling point of the solvent, from 1 to 24. It is manufactured by reacting for hours. Examples of the solvent used in this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; Examples include ethers such as THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, non-protonic polar solvents such as DMF and DMSO, and acetonitrile. The base used in this reaction includes sodium carbonate, carbonated carbonate and the like, sodium hydroxide-hydroxide hydroxide and other metal hydroxides, and sodium methyler. Metal alkoxides such as sodium and sodium hydride, metal hydrides such as sodium hydride and hydrogen hydride, lithium amides such as lithium diisopropylamide, and organic bases such as triethylamine and DBU. And the like. (In the formula, R 8. R 8 represents the same meaning as described above.)
f ) ォキサゾール 〔 1 h〕 の製造法 f) Preparation of oxazole [1h]
Figure imgf000031_0001
Figure imgf000031_0001
一般式 〔6 3〕 で示されるアルデヒ ドとイソ二ト リノレ 〔3 8〕 をアルデヒ ドに 対して 2等量以上の適当な塩基の存在下、 適当な溶媒中、 室温〜溶媒の沸点未満 の温度で 1〜2 4時間反応させることにより製造される。 この反応に用いられる 溶媒としては、 例えば、 メタノール、 エタノール、 イソプロパノール等のアルコ ール類、 ベンゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロロホ ルム等のハロゲン化炭化水素類、 ジェチルエーテル、 THF等のエーテル類、 D MF, DMS 0等の非プロ トン性極性溶媒、 ァセ トニト リル等が挙げられる。 又、 この反応に用いられる塩基としては、 炭酸ナト リウム、 炭酸カリウム等の炭酸塩 類、 水酸化ナトリウム、 水酸化力リゥム等の水酸化金属類、 ナト リ ウムメチラ一 ト、 ナ ト リゥムェチラ一ト等の金属アルコラ一ト類、 水素化ナト リ ゥム、 水素化 カリウム等の水素化金属類、 リチウムジイソプロピルアミ ド、 リチウムビス ト リ メチルシリルァミ ド等のリチウムアミ ド類、 卜 リェチルァミ ン、 D B U等の有機 塩基類等が挙げられる。 （式中、 R22は前記と同じ意味を表す。 ） The aldehyde represented by the general formula [63] and the isonitrinole [38] are reacted with the aldehyde in the presence of at least two equivalents of a suitable base in a suitable solvent at room temperature to below the boiling point of the solvent. It is produced by reacting at a temperature for 1 to 24 hours. Solvents used in this reaction include, for example, alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chloroform; dimethyl ether; Examples include ethers such as THF, non-protonic polar solvents such as DMF and DMS0, and acetonitrile. Examples of the base used in this reaction include carbonates such as sodium carbonate and potassium carbonate, metal hydroxides such as sodium hydroxide and hydroxide rim, sodium methylate, sodium methylate and the like. Metal alkoxides, sodium hydride, metal hydrides such as potassium hydride, lithium diisopropylamide, lithium amides such as lithium bistrimethylsilylamide, organic compounds such as triethylamine and DBU Bases and the like. (Wherein, R 22 has the same meaning as described above.)
g) ォキサゾ一ル 〔 1 i〕 の製造法 P T/JP94/00109 g) Production method of oxazole [1i] PT / JP94 / 00109
3 0 3 0
Figure imgf000032_0001
Figure imgf000032_0001
一般式 〔6 4〕 で示されるァシルイ ミダゾールとイソ二ト リル類を適当な塩基 の存在下、 適当な溶媒中、 一 7 8〜 8 0での温度で 1〜 2 4時間反応させること により 〔 1 i〕 が製造される。 この反応に用いられる溶媒としては、 例えば、 ベ ンゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホルム等のハ ロゲン化炭化水素類、 ジェチルエーテル、 THF等のエーテル類、 DMF， DM S 0等の非プロ トン性極性溶媒、 ァセ トニ卜 リル等が挙げられる。 又、 この反応 に用いられる塩基としては、 炭酸ナト リゥ厶、 炭酸力リゥム等の炭酸塩類、 水酸 化ナ ト リ ウム、 水酸化力リゥム等の水酸化金属類、 水素化ナ ト リウム、 水素化力 リ ウム等の水素化金属類、 リチウムジイソプロピルアミ ド、 リチウムピス ト リ メ チルシリルァミ ド等のリチウムアミ ド類、 卜 リェチルァミ ン、 D B U等の有'機塩 基類等が挙げられる。 （式中、 R20は前記と同じ意味を表す。 ) By reacting the acylimidazole represented by the general formula [64] with isonitriles in the presence of a suitable base in a suitable solvent at a temperature of 178 to 80 for 1 to 24 hours, 1 i] is manufactured. Solvents used in this reaction include, for example, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as dichloromethane and chloroform, ethers such as getyl ether and THF, DMF, DM Non-protonic polar solvents such as S0 and acetonitril. The base used in this reaction includes sodium carbonate, sodium carbonate and the like, sodium hydroxide, metal hydroxide such as sodium hydroxide, sodium hydride, hydrogen hydride and the like. Metal hydrides such as lithium, lithium amides such as lithium diisopropylamide and lithium pristylmethylsilylamide, organic salts such as triethylamine and DBU, and the like. (Wherein, R 20 represents the same meaning as described above.)
h) ォキサゾリ ン 〔 1 j〕 の製造法 h) Production method of oxazoline [1j]
Figure imgf000032_0002
一般式 〔6 3〕 で示されるアルデヒ ドとイソ二ト リル 〔3 8〕 をアルデヒ ドに 対してほぼ等量の適当な塩基の存在下、 適当な溶媒中、 0°C〜室温の温度で 1〜 2時間反応させることにより 〔 1 j〕 が製造される。 この反応に用いられる溶媒 と しては、 例えば、 メタノール、 エタノール、 イソプロパノール等のアルコール 類、 ベンゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホルム 等のハロゲン化炭化水素類、 ジェチルエーテル、 THF等のエーテル類、 DMF, DM S 0等の非プロ トン性極性溶媒、 ァセ トニト リル等が挙げられる。 又、 この 反応に用いられる塩基としては、 炭酸ナト リウム、 炭酸カリウム等の炭酸塩類、 水酸化ナ ト リ ウム、 水酸化力リゥム等の水酸化金属類、 水素化ナト リウム、 水素 化カリ ウム等の水素化金属類、 リチウムジイソプロピルアミ ド、 リチウムピス ト リメチルシリルァミ ド等のリチウムアミ ド類、 ト リェチルァミ ン、 D B U等の有 機塩基類等が挙げられる。 （式中、 R22は前記と同じ意味を表す。 )
Figure imgf000032_0002
The aldehyde represented by the general formula [63] and isonitrile [38] are reacted in a suitable solvent in the presence of a suitable base in an amount equivalent to the aldehyde at a temperature of 0 ° C to room temperature. [1j] is produced by reacting for 1 to 2 hours. Examples of the solvent used in this reaction include alcohols such as methanol, ethanol, and isopropanol; aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as dichloromethane and chromatoform; and dimethyl ether. And ethers such as THF, non-protonic polar solvents such as DMF and DMSO, and acetonitrile. Examples of the base used in this reaction include carbonates such as sodium carbonate and potassium carbonate, metal hydroxides such as sodium hydroxide and hydrating power, sodium hydride, potassium hydride and the like. Metal hydrides, lithium amides such as lithium diisopropylamide and lithium pristylmethylsilylamide, and organic bases such as triethylamine and DBU. (Wherein, R 22 has the same meaning as described above.)
i ) ォキサジァゾール 〔 l k〕 の製造法  i) Preparation of oxaziazole [lk]
Figure imgf000033_0001
Figure imgf000033_0001
一般式 〔6 4〕 で示されるァシルイ ミダゾールとアミ ドキシム 〔4 8〕 を適当 な塩基の存在下、 適当な溶媒中、 — 1 5〜 1 4 0 °Cの温度で 1〜 24時間反応さ せることにより 〔 l k〕 が製造される。 この反応に用いられる溶媒としては、 例 えば、 ベンゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホル ム等のハロゲン化炭化水素類、 ジェチルエーテル、 THF等のエーテル類、 DM F, DM S 0等の非プロ トン性極性溶媒、 ァセ トニ ト リル等が挙げられる。 又、 この反応に用いられる塩基としては、 炭酸ナ ト リ ウム、 炭酸カリウム等の炭酸塩 類、 水酸化ナト リ ウム、 水酸化力リゥム等の水酸化金属類、 水素化ナ ト リ ウム、 水素化カリ ウム等の水素化金属類、 リチウムジイソプロピルアミ ド等のリチウム アミ ド類、 ト リェチルァミ ン、 DBU等の有機塩基類等が挙げられる。 （式中、 R25は前記と同じ意味を表す。 ） The acylimidazole represented by the general formula [64] and the amide oxime [48] are reacted in a suitable solvent in the presence of a suitable base at a temperature of 15 to 140 ° C for 1 to 24 hours. This produces [lk]. Solvents used in this reaction include, for example, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as dichloromethane and chloroform, ethers such as getyl ether and THF, DMF, Non-protonic polar solvents such as DMSO, acetonitril, and the like. Examples of the base used in this reaction include carbonates such as sodium carbonate and potassium carbonate, metal hydroxides such as sodium hydroxide and hydroxide hydroxide, sodium hydride, and hydrogen. Metal hydrides such as potassium iodide, and lithium such as lithium diisopropylamide Examples include amides, triethylamine, and organic bases such as DBU. (Wherein, R 25 has the same meaning as described above.)
(製造方法一 3)  (Production method 1)
試 剤 Reagent
塩 基 Base
Figure imgf000034_0001
Figure imgf000034_0001
一般式 〔 1 ' 〕 で示される化合物を、 文献公知の方法に従い、 適当な塩基、 も しく は酸の存在下、 無溶媒又は適当な溶媒中、 一 7 8 °C〜溶媒の沸点未満の温度 で、 適当な試剤 （例えば、 ヨウ化メチル等のアルキル化剤、 ァセチルクロリ ドの ようなァシル化剤、 メタンスルホニルクロリ ドのようなスルホ二ル化剤等） と、 1 ~ 24時間反応させ、 ヘテロ環 Q ' 上の置換基 Y' n ' もしく はベンゼン環 （ ピリ ジン環） 上の置換基 X' m' を誘導化して 〔 1〕 を合成する。 （但し、 式中 、 R, ， R2 ， A, B, Q, X， Y, Z, m, nは前記と同じ意味を表し、 Q ' , Χ' , Υ' , m' , η' はそれぞれ Q, X， Y， m, nと同意味を示す。 ） a ) ォキサゾリ ン The compound represented by the general formula [1 '] is reacted with a suitable base or acid in the absence of a solvent or in a suitable solvent at a temperature of from 178 ° C to a temperature lower than the boiling point of the solvent, according to a method known in the literature. And reacting with an appropriate reagent (eg, an alkylating agent such as methyl iodide, an acylating agent such as acetyl chloride, a sulfonylating agent such as methanesulfonyl chloride) for 1 to 24 hours, [1] is synthesized by derivatizing the substituent Y'n 'on the ring Q' or the substituent X'm 'on the benzene ring (pyridin ring). (Wherein, R,, R 2 , A, B, Q, X, Y, Z, m, n represent the same meaning as described above, and Q ′, Χ ′, Υ ′, m ′, η ′ Each has the same meaning as Q, X, Y, m, n.) A) Oxazoline
Figure imgf000034_0002
Figure imgf000034_0002
Ζ2:0， S Ζ 2 : 0, S
一般式 〔 1 j〕 の化合物と 〔6 5〕 を適当な塩基の存在下、 適当な溶媒中、 一 1 5-2 5 の温度で 1〜 24時間反応させることにより 〔 1 1〕 が製造される c この反応に用いられる溶媒と しては、 例えば、 メタノール、 エタノール、 イソプ ロバノール等のアルコール類、 ベンゼン、 トルエン等の芳香族炭化水素類、 ジク ロロメタン、 クロ口ホルム等のハロゲン化炭化水素類、 ジェチルェ一テル、 TH F等のエーテル類、 アセ トン、 MEK等のケ トン類、 酢酸メチル、 酢酸ェチル等 のエステル類、 DMF， DMS 0等の非プロ トン性極性溶媒、 ァセ トニ ト リル、 水等が挙げられる。 又、 この反応に用いられる塩基としては、 炭酸ナ ト リ ウム、 炭酸力リゥム等の炭酸塩類、 水酸化ナ ト リ ウム、 水酸化力リゥム等の水酸化金属 類、 ナ ト リ ウムメチラー ト、 ナ ト リ ウムェチラー ト等の金属アルコラ一ト類、 水 素化ナ ト リ ウム、 水素化カリ ウム等の水素化金属類、 リチウムジイソプロピルァ ミ ド、 リチウムピス ト リ メチルシリルアミ ド等のリチウムアミ ド類、 ト リェチル アミ ン、 D BU等の有機塩基類等が挙げられる。 （式中、 Z2 は酸素、 硫黄を表 し、 R30はアルキル、 ァリールを表し、 R22は前記と同じ意味を表す。 ） (11) is produced by reacting the compound of the general formula (1j) with (65) in the presence of a suitable base in a suitable solvent at a temperature of 15-25 for 1 to 24 hours. that c is a solvent used in this reaction, for example, alcohols such as methanol, ethanol and isoprene Robanoru, benzene, aromatic hydrocarbons such as toluene, dichloroethylene Rorometan, halogenated hydrocarbons such as black hole Holm , Jettlätel, TH Examples include ethers such as F, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, non-protonic polar solvents such as DMF and DMS 0, acetonitrile, and water. . Examples of the base used in this reaction include sodium carbonate, carbonates such as carbonated lime, sodium hydroxide, metal hydroxides such as hydroxylated lime, sodium methylate, and sodium methylate. Metal alcohols such as triethyl ethylate; metal hydrides such as sodium hydride and potassium hydride; lithium amides such as lithium diisopropyl amide and lithium p-methylsilyl amide And organic bases such as triethylamine and DBU. (In the formula, Z 2 represents oxygen or sulfur, R 30 represents alkyl or aryl, and R 22 represents the same meaning as described above.)
(製造方法一 4 )  (Manufacturing method 1)
Figure imgf000035_0001
一般式 〔2〕 （式中、 R, ， R2 ， A, Lは前記と同じ意味を表す。 ） の化合 物と、 一般式 〔6 6〕 （式中、 B, Q, X, Y, m， nは前記と同じ意味を表す。） の化合物を、 有機溶媒中で塩基の存在下カップリ ングさせる。 塩基としては、 水 素化ナ ト リウム等の水素化金属類、 炭酸カリウム等の炭酸塩類、 ト リェチルアミ ン等の有機塩基類であり、 溶媒としては、 DMF， DMS 0, THF， DME等 が挙げられる。 反応混合物は反応が完了するまで、 0~9 0°C、 場合によっては 1 2 0 °Cで撹拌される。
Figure imgf000035_0001
A compound of the general formula [2] (wherein, R,, R 2 , A and L represent the same meaning as described above); and a compound of the general formula [66] (where B, Q, X, Y, m and n represent the same meaning as described above.) in an organic solvent in the presence of a base. Examples of the base include metal hydrides such as sodium hydride, carbonates such as potassium carbonate, and organic bases such as triethylamine. Examples of the solvent include DMF, DMS0, THF, and DME. Can be The reaction mixture is stirred at 0 to 90 ° C, and in some cases at 120 ° C, until the reaction is completed.
上記の反応における原料の 0 _ヘテロ環置換チオール （あるいは、 メルカプト ピリ ジン） 誘導体 〔 6 6〕 は以下に述べるような方法により製造することができ る。 尚、 特に指定をしていない場合に於いては以下の反応で用いられる溶媒とし ては、 メタノール、 エタノール、 イソプロピルアルコール等のアルコール類、 ベン ゼン、 トルエン等の芳香族炭化水素類、 ジクロロメタン、 クロ口ホルム等のハロ ゲン化炭化水素類、 ジェチルエーテル、 TH F等のエーテル類、 アセ トン、 ME K等のケ トン類、 酢酸メチル、 酢酸ェチル等のエステル類、 DMF, DMS O等 の非プロ トン性極性溶媒、 ァセ トニト リル等の二ト リル類、 、 水等が挙げられる 。 又、 用いられる塩基としては、 炭酸ナト リゥム、 炭酸力リ ゥム等の炭酸塩類、 水酸化ナト リ ウム、 水酸化力リゥム等の水酸化金属類、 ナ ト リ ウムメチラー ト、 ナ ト リ ウムェチラ一 卜等の金属アルコラ一 卜類、 水素化ナト リ ゥム等の水素化金 属類、 ブチルリチウム等のアルキル金属類、 リチウムジイソプロピルアミ ド、 リ チウムビス ト リメチルシリルァミ ド等のリチウムアミ ド類、 ト リェチルァミ ン、 D BU等の有機塩基類等が挙げられる。 又、 用いられる酸としては塩酸、 硝酸、 硫酸等の鉱酸類、 蟻酸、 酢酸等の有機酸類、 塩化アルミニウム、' ボロン ト リフロ リ ドジェチルエーエル等のルイス酸類が挙げられる。 又、 反応温度としては、 一 9 0 °C〜 2 5 0 °Cの温度が挙げられる。 （以下、 式中 Q, X， Y, m, n, Bは 前記と同じ意味を表す。 ） The 0-heterocyclic-substituted thiol (or mercapto pyridine) derivative [66] as the raw material in the above reaction can be produced by the method described below. Unless otherwise specified, solvents used in the following reactions include alcohols such as methanol, ethanol, and isopropyl alcohol, aromatic hydrocarbons such as benzene and toluene, dichloromethane, and chloroform. Halo such as mouth form Genated hydrocarbons, ethers such as getyl ether and THF, ketones such as acetone and MEK, esters such as methyl acetate and ethyl acetate, and non-protonic polar solvents such as DMF and DMS O And nitriles such as acetonitril, and water. Examples of the base to be used include carbonates such as sodium carbonate and carbonated carbonate, sodium hydroxide, metal hydroxides such as hydroxided sodium, sodium methylate, and sodium ethylate. Metal alcohols such as metal, hydrogenated metals such as sodium hydride, alkyl metals such as butyllithium, lithium amides such as lithium diisopropylamide and lithium bistrimethylsilylamide And organic bases such as triethylamine, DBU and the like. Examples of the acid used include mineral acids such as hydrochloric acid, nitric acid and sulfuric acid, organic acids such as formic acid and acetic acid, aluminum chloride, and Lewis acids such as boron trifluoride dodecyl ether. The reaction temperature is, for example, a temperature of 190 ° C to 250 ° C. (Hereinafter, Q, X, Y, m, n, and B represent the same meaning as described above.)
〔68〕 (68)
JMe:
Figure imgf000036_0001
JMe:
Figure imgf000036_0001
〔 3〕 〔69〕 〔70〕  (3) (69) (70)
Figure imgf000036_0002
Figure imgf000036_0002
〔71〕 〔66〕 上述の、 化合物 〔3〕 の合成法に準じた方法で製造する事の出来る、 一般式 〔6 8〕 の化合物に硫化ナトリウムやチォゥレア等を反応させて、 化合物 〔6 6〕 を製造することが出来る。 この反応の参考文献としては、 C h em i s t r y L e t t e r s, 1 3 0 7ページ （ 1 9 8 5年） が挙げられる。 (71) (66) Compound (66) can be produced by reacting a compound of the general formula (68) with sodium sulfide or thioperia, which can be produced by a method similar to the method for synthesizing compound (3) described above. I can do it. References for this reaction include Chemistry Letters, page 1307 (1985).
あるいは、 〔6 6〕 は、 前述の化合物 〔3〕 を 〔6 9〕 に誘導した後、 J. 0 r g. C h e m. 3 1巻、 3 9 8 0ページ （ 1 9 6 6年） に記載された、 ニュー マン転位反応により 〔7 0〕 として、 これを加水分解する事によっても製造する ことが出来る。  Alternatively, [66] is obtained by deriving the above-mentioned compound [3] to [69], and then applying the method described in J. 0 rg. Chem. 31 Volume 1, p. 398 (1966) The compound can also be produced by hydrolyzing this as [70] by the Newman rearrangement reaction described in (1).
又、 ァニリ ン誘導体 〔 7 1〕 を 0 r g a n i c S y n t h e s e s C o l In addition, the aniline derivative [71] was converted to 0 r g a n i c S y n t h e se s C o l
1 e c t . , 3巻、 8 0 9ページに記載の方法を応用しても、 〔6 6〕 を製造す ることが出来る。 （式中、 L4 はハロゲン、 好ましくはフッ素を表す。 ） [66] can also be produced by applying the method described in 1 ect., Volume 3, page 809. (In the formula, L 4 represents halogen, preferably fluorine.)
(製造法一 5 )  (Production method 5)
Figure imgf000037_0001
Figure imgf000037_0001
〔68〕 〔72〕 〔 1〕  (68) (72) (1)
一般式 〔7 2〕 （式中、 R, ， R2 ， A, Zは一前記と同じ意味を表す。 ) の 化合物と、 一般式 〔6 8〕 （式中、 B, Q, X, Y, m, n， L4 は前記と同じ 意味を表す。 ） の化合物を、 有機溶媒中で塩基の存在下カップリングさせる。 塩 基としては、 水素化ナトリゥム等の水素化金属類、 炭酸力リゥム等の炭酸塩類、 トリヱチルァミ ン等の有機塩基類であり、 溶媒としては、 DMF， DMS O, T HF， DME等が挙げられる。 反応混合物は反応が完了するまで、 0〜9 0°C、 場合によっては 1 2 0°Cで撹拌される。 A compound of the general formula [72] (wherein R,, R 2 , A and Z represent the same meaning as described above), and a compound of the general formula [68] (where B, Q, X, Y , m, n, L 4 is a compound of representing.) as defined above, is the presence coupling base in an organic solvent. Examples of the base include metal hydrides such as sodium hydride, carbonates such as carbonated lime, and organic bases such as tritylamine. Examples of the solvent include DMF, DMS O, THF, and DME. . The reaction mixture is stirred at 0-90 ° C, optionally at 120 ° C, until the reaction is complete.
一般式 〔 1〕 で表される化合物の塩としては、 環境容認性の塩、 例えば、 塩酸 塩、 臭化水素塩等の無機酸塩類、 酢酸塩、 蓚酸塩、 蟻酸塩等の有機酸塩類等、 及 びアルカリ金属、 アルカリ土類金属、 アンモニゥム塩等が挙げられる。 これらの 塩は慣用の方法で製造し得る。 本発明化合物の構造は、 I R， NMR， MS等から決定した。 Examples of the salt of the compound represented by the general formula [1] include environmentally acceptable salts, for example, inorganic acid salts such as hydrochloric acid salt and hydrogen bromide salt, and organic acid salts such as acetate, oxalate, and formate. And alkaline metals, alkaline earth metals, ammonium salts and the like. These salts can be prepared in a conventional manner. The structure of the compound of the present invention was determined from IR, NMR, MS and the like.
発明を実施するための最良の形態： BEST MODE FOR CARRYING OUT THE INVENTION
次に実施例を挙げ本発明化合物を更に詳細に説明する。  Next, the compound of the present invention will be described in more detail with reference to examples.
実施例 1 Example 1
1 —メチル一 4— ( 2— （ 4， 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フエニル） ビラゾール （化合物番号 1 4— 1 3 ) の合成  Synthesis of 1-Methyl-1- (2- (4,6-Dimethoxypyrimidine-1-2-yloxy) phenyl) virazole (Compound No. 14-14)
Figure imgf000038_0001
Figure imgf000038_0001
2 - ( 1 —メチルーピラゾールー 4一ィル） フエノール 0. 3 2 gを DMF 5 m 1に溶解し、 6 0 %N a H 0. 1 gを加え、 5 0 °Cで 3 0分間、 撹拌した。 次 いで、 2—メタンスルホ二ルー 4 , 6—ジメ トキシピリ ミ ジン 0. 4 5 gを加え、 5 0 °Cで 3 0分間撹拌した後、 室温で 1 4時間撹拌した。 反応終了後、 溶媒を減 圧下留去し、 得られた残査を酢酸ェチル—水に溶解し、 有機層を水洗、 次いで無 水硫酸マグネシウムで乾燥した。 濾過後、 溶媒を減圧下留去し、 得られた残査を カラムクロマト （シリカゲル；溶出溶媒：へキサンーァセトン = 8— 2 ) で精製 し、 目的物 0. 3 1 gを得た。  2-(1 -Methyl-pyrazole-4-yl) Dissolve 0.32 g of phenol in 5 ml of DMF, add 0.1 g of 60% NaH, and 30 minutes at 50 ° C Stirred. Next, 0.45 g of 2-methanesulfonyl-4,6-dimethoxypyrimidine was added, and the mixture was stirred at 50 ° C. for 30 minutes and then at room temperature for 14 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and the obtained residue was dissolved in ethyl acetate-water. The organic layer was washed with water and dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (silica gel; elution solvent: hexaneacetone = 8-2) to obtain 0.31 g of the desired product.
実施例 2 Example 2
3—シァノ ー 4 一 （ 2— （ 4 , 6—ジメ 卜キシピリ ミ ジン一 2—ィルォキシ） フエニル） ピロール （化合物番号 1 7— 2 ) の合成  Synthesis of 3-cyano 41- (2— (4,6-dimethylmethoxypyrimidine-1-2-yloxy) phenyl) pyrrole (Compound No. 17—2)
Figure imgf000038_0002
2— （ 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） 桂皮二 ト リノレ 1. 1 2と丁 0 51^ 1 じ 0. 7 6 gの TH F 1 0 m 1溶液を、 窒素気流中、 撹拌下、 6 0 %N a H 0. 1 8 gの THF l O m l懸濁液に滴下した。 室温で 1時間撹拌し た後、 氷水に注入し、 次いで酢酸ェチルを加え抽出した。 有機層を水洗、 次いで 無水硫酸マグネシウムで乾燥した。 濾過後、 溶媒を減圧下留去した。 得られた残 査をカラムクロマ ト （シリ 力ゲル ； 溶出溶媒 ： へキサン—ァセ ト ン = 8— 2 ) で 精製し、 目的物 0. 3 2 gを得た。
Figure imgf000038_0002
2— (4,6-Dimethoxypyrimidine-1—2-yloxy) Cinnamon 2 Trinole 1.12 and 0.15 1 1 0.76 g of THF 10 ml solution in a stream of nitrogen Under stirring, a suspension of 60% NaH 0.18 g in THF 10 ml was added dropwise. After stirring at room temperature for 1 hour, the mixture was poured into ice water, and then ethyl acetate was added for extraction. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography (silica gel; elution solvent: hexane-aceton = 8-2) to obtain 0.32 g of the desired product.
実施例 3 Example 3
4 —メチル一 5— （ 2—クロル一 6— ( 2— （ 4 , 6—ジメ 卜キシピリ ミ ジン 一 2—ィルォキシ） フヱニル） ォキサゾ一ル （化合物番号 1 3— 8 0 ) の合成  Synthesis of 4-Methyl-5- (2-Chloro-6- (2- (4,6-Dimethoxypyrimidine-12-yloxy) phenyl) oxazole (Compound No. 13-80)
Figure imgf000039_0001
Figure imgf000039_0001
2— （ 4 —メチルォキサゾ一ル一 5—ィル） 一 3—クロ口フエノール 0. 2 5 g、 2 —メ タンスルホ二ルー 4 , 6—ジメ トキシピリ ミ ジン 0. 1 9 gと炭酸力 リウム 0. 4 2 gの DMF 5 m l溶液を 5 0 で 1 4時間撹拌した。 反応終了後、 反応液を氷水に注入し、 次いで酢酸ェチルを加え抽出した。 有機層を水洗、 次い で無水硫酸マグネシウムで乾燥した。 濾過後、 溶媒を減圧下留去し、 目的物 3 4 gを得た。  2- (4-Methyloxazole-1-5-yl) 1-3-Chlorophenol 0.25 g, 2—Methanesulfonyl 4,6, -Dimethoxypyrimidine 0.19 g and potassium carbonate 0 A solution of 42 g of DMF in 5 ml was stirred at 50 for 14 hours. After completion of the reaction, the reaction solution was poured into ice water, and then ethyl acetate was added for extraction. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure to obtain 34 g of the desired product.
実施例 4 Example 4
1 —ベンジル一 5— ( 4 , 6—ジメ トキシピリ ミ ジン一 2 —ィルォキシ） フエ ニル） ィミダゾ一ル （化合物番号 2 - 1 3 ) の合成
Figure imgf000040_0001
1—Benzyl-5- (4,6-dimethoxypyrimidine-2- (yloxy) phenyl) imidazole (Compound No. 2-13)
Figure imgf000040_0001
2 - ( 1一べンジルイ ミダゾ一ル一 5 _ィル） フエノール 2. 5 g、 2—メタ ンスルホニルー 4, 6—ジメ トキシピリ ミ ジン 2. 2 gと炭酸カリウム 2. 7 6 gの DMF 2 0 m 1溶液を 5 0°Cで 1 4時間撹拌した。 反応終了後、 反応液を氷 水に注入し、 次いで酢酸ェチルを加え抽出した。 有機層を水洗、 次いで無水硫酸 マグネシウムで乾燥した。 濾過後、 溶媒を減圧下留去し、 得られた残留物をカラ ムクロマ ト （シリカゲル ；溶出溶媒：塩化メチレン一アセ トン = 8 5— 1 5) で 精製し、 目的物 2. 7 5 gを得た。  2- (1 benzoylimidazole-5-yl) phenol 2.5 g, 2-methanesulfonyl-4,6-dimethoxypyrimidine 2.2 g and potassium carbonate 2.76 g DMF 20 The m1 solution was stirred at 50 ° C. for 14 hours. After completion of the reaction, the reaction solution was poured into ice water, and then ethyl acetate was added for extraction. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (silica gel; elution solvent: methylene chloride-acetone = 85-15) to give 2.75 g of the desired product Obtained.
実施例 5 Example 5
2—メチル一 5— (2—フルオロー 6— (4， 6—ジメ トキシピリ ミ ジン _ 2 一ィルォキシ） フヱニル） ォキサゾール （化合物番号 1 3— 1 0 2) の合成  Synthesis of 2-methyl-5- (2-fluoro-6- (4,6-dimethoxypyrimidine_2-yloxy) phenyl) oxazole (Compound No. 13-3-102)
Figure imgf000040_0002
Figure imgf000040_0002
2 - ( 2—メチルォキサゾ一ルー 5—ィル） 一 3—フルオロフエノ一ル 0. 1 2 g、 2—メタンスルホ二ルー 4 , 6—ジメ トキシピリ ミ ジン 0. 1 2 gと炭酸 カリ ウム 0. 1 8 gの DMF 4m l溶液を 5 0 °Cで 1 4時間撹拌した。 反応終了 後、 反応液を氷水に注入し、 次いで酢酸ェチルを加え抽出した。 有機層を水洗、 次いで無水硫酸マグネシウムで乾燥した。 濾過後、 溶媒を減圧下留去し、 得られ た残査を石油エーテルで処理し、 目的物 0. 1 gを得た。  2- (2-methyloxazolyl 5-yl) 1-3-fluorophenol 0.12 g, 2-methanesulfonyl 4,6, -dimethoxypyrimidine 0.12 g and potassium carbonate 0.1 8 g of a 4 ml solution of DMF was stirred at 50 ° C. for 14 hours. After completion of the reaction, the reaction solution was poured into ice water, and then ethyl acetate was added for extraction. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the obtained residue was treated with petroleum ether to obtain 0.1 g of the desired product.
実施例 6 3— ( 2 - ( 4， 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フエニル） ― 2—ィソォキサゾリン （化合物番号 4 - 1 2) の合成 Example 6 Synthesis of 3- (2- (4,6-Dimethoxypyrimidine-1-2-yloxy) phenyl) -2-isosoxazoline (Compound No. 4-1-2)
Figure imgf000041_0001
Figure imgf000041_0001
2 - ( 2—イソォキサゾリン一 5—ィル） フエノ ル 0 6 gと 4， 6—ジメ トキシー 2—メタンスルホニルピリ ミ ジン 0. 7 8 gを DM Fに溶解し、 撹拌下、 室温にて6 0%N aH 0. 1 6 gを加え、 3 0 ~ 4 0 °Cで 2. 5時間撹拌した。 反応終了後、 反応液を氷水に注入し、 濾別した。 得られた結晶を酢酸ェチルに溶 解し、 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去した。 得られた結晶を n—へキサンで洗浄し、 目的物 l gを得 た。  Dissolve 0.66 g of 2- (2-isoxazoline-1-yl) phenol and 0.78 g of 4,6-dimethoxy-2-methanesulfonylpyrimidine in DMF and stir at room temperature under stirring. 0.16 g of 0% NaH was added, and the mixture was stirred at 30 to 40 ° C for 2.5 hours. After completion of the reaction, the reaction solution was poured into ice water and filtered. The obtained crystals were dissolved in ethyl acetate, and the organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained crystals were washed with n-hexane to obtain the desired product (lg).
実施例 7 Example 7
5— ( 2 - ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フエニル） ィ ソォキサゾール （化合物番号 5— 1 2 ) の合成  Synthesis of 5- (2- (4,6-dimethoxypyrimidine-1-2-yloxy) phenyl) isoxazole (Compound No. 5-12)
Figure imgf000041_0002
Figure imgf000041_0002
6 0 %N a H 0. 1 1 gを DM Fに懸濁させ、 撹拌下、 5 °Cにて 2— (イソォ キサゾール— 5—ィル） フヱノール 0. 4 gの DMF溶液を滴下した。 3 0~4 0 °Cで 3 0分間撹拌し、 次いで、 4, 6—ジメ トキシ一 2—メタンスルホ二ルビ リ ミジン 0. 5 3 gを加え、 室温で 5時間撹拌した。 反応終了後、 反応液を氷水 に注入し、 酢酸ェチルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水硫 酸マグネシウムで乾燥した後、 溶媒を減圧下留去した。 得られた残査をカラムク ロマ卜にて精製し、 目的物 3 gを得た。 0.11 g of 60% NaH was suspended in DMF, and a DMF solution of 0.4 g of 2- (isoxazole-5-yl) phenol was added dropwise at 5 ° C. with stirring. The mixture was stirred at 30 to 40 ° C. for 30 minutes, and then 0.53 g of 4,6-dimethoxy-12-methanesulfonylbilimidine was added, followed by stirring at room temperature for 5 hours. After the completion of the reaction, the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue is collected Purification by chromatography gave 3 g of the desired product.
実施例 8 Example 8
1一 （4， 6—ジメ トキシピリ ミ ジン一 2—ィル） 一 2— （2— (4， 6—ジ メ トキシピリ ミ ジン一 2—ィルォキシ） フヱニル） ベンズイ ミ ダゾール （化合物 番号 1一 1 2 ) の合成  1- (4,6-Dimethoxypyrimidine 1-2-yl) 1 2- (2- (4,6-Dimethoxypyrimidine-1-2-yloxy) phenyl) Benzimidazole (Compound No. 1-11-2) Synthesis of
Figure imgf000042_0001
Figure imgf000042_0001
6 0 %N a H 0. 2 1 gを DMFに懸濁させ、 撹拌下、 室温にて 2 - ィミダゾールー 2—ィル） フエノール 1 gの DMF溶液を滴下した。 3 0 ~ 4 0 °Cで 3 0分間撹拌し、 次いで、 4, 6—ジメ 卜キシ一 2—メタンスルホニルピリ ミ ジン 1. 0 1 gを加え、 4 0°Cで 4時間撹拌した。 反応終了後、 反応液を氷水 に注入し、 酢酸ェチルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水硫 酸マグネシウムで乾燥した後、 溶媒を減圧下留去した。 得られた残査をカラムク 口マ トにて精製し、 目的物 0. l gを得た。  60% NaH 0.21 g was suspended in DMF, and a DMF solution of 1 g of 2-imidazole-2-yl) phenol was added dropwise at room temperature with stirring. The mixture was stirred at 30 to 40 ° C for 30 minutes, and then 1.01 g of 4,6-dimethyloxy-2-methanesulfonylpyrimidine was added, followed by stirring at 40 ° C for 4 hours. After the completion of the reaction, the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified with a column chromatography to obtain 0.1 g of the desired product.
実施例 9 Example 9
5— ( 2 - (4, 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） 一 6—フエノ キシ） フエ二ルォキサゾ一ル （化合物番号 2 0— 2 2 ) の合成  Synthesis of 5- (2- (4,6-dimethoxypyrimidine-1-2-yloxy) -1-6-phenoxy) phenyloxazole (Compound No. 20-22)
0 N OMe0 N OMe
Figure imgf000042_0002
N、
Figure imgf000042_0002
N,
OMe  OMe
2 - '一ル— 5—ィル） — 3 フエノキシフエノール 0. 4 3 gと炭 酸カリウム 0. 4 7 gを DMFに懸濁させ、 3 0~4 0°Cで 3 0分間撹拌した後 4， 6—ジメ トキシ一 2 _メ タンスルホニルピリ ミ ジン 0. 3 6 gを加え、 5 0 °Cで一晩撹拌した。 反応終了後、 反応液を氷水に注入し、 酢酸ェチルで抽出した c 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒 を減圧下留去して、 目的物 0. 3 9 gを得た。 2-'1-5-yl)-3 0.4 g of phenoxyphenol and 0.47 g of potassium carbonate are suspended in DMF and stirred at 30 to 40 ° C for 30 minutes. After that, 0.36 g of 4,6-dimethoxy-2-methansulfonylpyrimidine was added, and 50 Stirred overnight at ° C. After completion of the reaction, the reaction mixture was poured into ice water, the c organic layer was extracted with acetic acid Echiru washed with water and saturated brine, dried over anhydrous magnesium sulfate, the solvent was evaporated off under reduced pressure, the desired product 0 39 g were obtained.
実施例 1 0 Example 10
4一 （ p— トルェンスルホニル） 一 5 _ ( 2 _ ( 4 , 6—ジメ トキシピリ ミ ジ ンー 2—ィルォキシ） 一 6—フエノキシフエニル） 一 2—ォキサゾリ ン （化合物 番号 2 7 - 2 0 ) の合成  4- (p-toluenesulfonyl) -5- (2_ (4,6-dimethoxypyrimidin-2-yloxy) -16-phenoxyphenyl) 1-2-oxazoline (Compound No. 27-7-20) Synthesis of
Figure imgf000043_0001
Figure imgf000043_0001
2 - (4, 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） 一 6—フエノキシベ ンズアルデヒ ド 0. 4 7 gとTo sM I C 0. 2 6 gをメタノールに懸濁させ、 撹拌下、 0てにて炭酸カリウム 0. 1 8 gを加え、 同温度で 1 5分撹拌した。 反 応終了後、 反応液を氷水に注入し、 濾別した。 得られた結晶を酢酸ェチルに溶解 し、 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去した。 得られた残査をベンゼン、 石油エーテルの混合溶媒で再 結晶させ、 目的物 5 gを得た。  2-(4,6-Dimethoxypyrimidine-1-2-yloxy)-1- 6-phenoxybenzaldehyde 0.47 g and TosM IC 0.26 g are suspended in methanol, and the suspension is stirred at room temperature. 0.18 g of potassium carbonate was added, and the mixture was stirred at the same temperature for 15 minutes. After completion of the reaction, the reaction solution was poured into ice water and filtered. The obtained crystals were dissolved in ethyl acetate, the organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was recrystallized from a mixed solvent of benzene and petroleum ether to obtain 5 g of the desired product.
実施例 1 1 Example 1 1
4一カルボキシル一 5— ( 2 - ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォ キシ） フエニル） ォキサゾール （化合物番号 1 3— 9) の合成  Synthesis of 4-carboxyl-5- (2- (4,6-dimethoxypyrimidine-12-yloxy) phenyl) oxazole (Compound No. 13-9)
Figure imgf000043_0002
Figure imgf000043_0002
( 2 ( 4， 6—ジメ トキシピリ ミ ジン一 2 ィルォキシ） フエニル） ォキサゾール 0. 6 9 gを TH Fに溶解し、 撹拌下、 ― 1 5 °Cにて 1 0 %N a OH水溶液を滴下し、 4 0 °Cで 2時間撹拌した。 反応終了 後、 反応液に 3 N— H C 1水溶液を加え、 酸性にした後、 酢酸ェチルで抽出した < 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒 を減圧下留去した。 得られた残査をエーテルで洗浄し、 目的物 0. 4 gを得た。 実施例 1 2 (2 (4,6-dimethoxypyrimidine 1 0.69 g of iloxy) phenyl) oxazole was dissolved in THF, a 10% aqueous NaOH solution was added dropwise at −15 ° C. with stirring, and the mixture was stirred at 40 ° C. for 2 hours. After completion of the reaction, the reaction solution was added with 3N-HC1 aqueous solution to make it acidic, and then extracted with ethyl acetate. <The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was decompressed. Distilled off under. The obtained residue was washed with ether to obtain 0.4 g of the desired product. Example 1 2
4—エトキシカルボ二ルー 5— ( 2 - ( 4， 6—ジメ 卜キシピリ ミ ジン一 2— ィルチオ） フヱニル） ォキサゾール （化合物番号 1 3— 1 6 0 ) の合成  Synthesis of 4-ethoxycarbonyl-5- (2- (4,6-dimethylmethoxypyrimidine-1-dithio) phenyl) oxazole (Compound No. 13—160)
( 2
Figure imgf000044_0001
(2
Figure imgf000044_0001
Fに溶解し、 撹拌下、 室温にて N, N' —カルボニルジイミダゾ一ル 1. 2 2 g を加え、 4 0~5 0°Cで 5 0分撹拌した。 この反応液を、 イソシァノ酢酸ェチル 1. 5 5 gの TH F溶液に、 撹拌下、 一 1 5 °Cにて D B U 2 gを滴下した直後、 一 5 °Cにて滴下し、 室温で二日間撹拌した。 反応終了後、 反応液を氷水に注入し、 3 0分撹拌した後、 エーテルと酢酸ェチルの混合溶媒で抽出した。 有機層を水及 び飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去 した。 得られた残査をカラムクロマ卜にて精製し、 目的物 1. 3 6 gを得た。 実施例 1 3 F, and 1.2 g of N, N'-carbonyldiimidazole was added at room temperature under stirring, and the mixture was stirred at 40 to 50 ° C for 50 minutes. This reaction solution was added dropwise to 1.55 g of THF solution of ethyl isocyanoacetate with stirring under stirring at 15 ° C immediately after adding 2 g of DBU at 15 ° C, and then dropped at 15 ° C for 2 days at room temperature. Stirred. After completion of the reaction, the reaction solution was poured into ice water, stirred for 30 minutes, and extracted with a mixed solvent of ether and ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography to obtain 1.36 g of the desired product. Example 13
5— （ 2 —アミ ノー 6— ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フ ニル） ォキサゾール （化合物番号 1 3— 1 1 8 ) の合成 9 Synthesis of 5— (2—Amino 6— (4,6-Dimethoxypyrimidine-1-2-yloxy) phenyl) oxazole (Compound No. 13—1 18) 9
4 3 4 3
Figure imgf000045_0001
Figure imgf000045_0001
鉄粉 0. 2 4 gを 6 0%酢酸水 3. 2 m 1に懸濁させ、 撹拌下、 5 0°Cにて 5 - (2— （4, 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） 一 6—二トロフエ ニル） ォキサゾール 0. 6 gの MEK溶液を滴下し、 6 0〜7 0°Cで 2時間撹拌 した。 反応終了後、 反応液に酢酸ェチルを加え、 濾過した。 濾液を水及び飽和食 塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去した。 得 られた残査をカラムクロマ 卜にて精製し、 目的物 0. 4 5 gを得た。  0.24 g of iron powder was suspended in 3.2 ml of 60% aqueous acetic acid and stirred at 50 ° C under stirring at 5 °-(2- (4,6-dimethoxypyrimidine-1-2-yloxy). ) 1-6-Trophenyl) oxazole 0.6 g of MEK solution was added dropwise and stirred at 60 to 70 ° C for 2 hours. After the reaction was completed, ethyl acetate was added to the reaction solution, followed by filtration. The filtrate was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography to obtain 0.45 g of the desired product.
実施例 1 4 Example 14
4ーメチルチオ一 5— (2— (4, 6—ジメ トキシピリ ミ ジン _ 2—ィルォキ シ） — 6—フルオロフヱニル） 一 2—ォキサゾリ ン （化合物番号 2 7— 1 4) の 合成  Synthesis of 4-methylthio-1-5- (2- (4,6-dimethoxypyrimidine_2-yloxy) —6-fluorophenyl) -12-oxazoline (Compound No. 27-14)
4— ( p— トルエンスルホニル） -- 5— 4— (p—Toluenesulfonyl)-5—
ン
Figure imgf000045_0002
一 2—ィルォキシ） 一 6—フルオロフヱ In
Figure imgf000045_0002
One 2-yloxy) one 6-fluorophenyl
の DM F溶液に、 撹拌下、 室温にて、 1 5 %メチルメルカプタンナ ト リゥム水溶 液 1. 4 gを滴下し、 同温度で 2 0分撹拌した。 反応終了後、 反応液に氷水を加 え、 エーテルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネ シゥムで乾燥した後、 溶媒を減圧下留去した。 得られた残査をカラムクロマ トに て精製し、 目的物 0. 1 9 gを得た。 実施例 1 5 1.4 g of a 15% aqueous solution of methyl mercaptan sodium was added dropwise to the DMF solution at room temperature under stirring at room temperature, followed by stirring at the same temperature for 20 minutes. After the reaction was completed, ice water was added to the reaction solution, and the mixture was extracted with ether. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography to obtain 0.19 g of the desired product. Example 15
2—メチルー 4 — ( 2— （ 4 , 6—ジメ トキシピリ ミ ジン一 2 —ィルォキシ） フユニル） チアゾール （化合物番号 2 1 — 5 ) の合成  Synthesis of 2-Methyl-4— (2— (4,6-Dimethoxypyrimidine-2- (yloxy) fuunyl) thiazole (Compound No. 21-5)
Me  Me
Figure imgf000046_0001
Figure imgf000046_0001
6 0 %N a H 0. 0 9 gを DMFに懸濁させ、 撹拌下、 室温にて、 2 _ ( 2 — メチルチアゾ一ル— 4—ィル） フエノール 0. 4 gの DMF溶液を滴下した。 3 0~4 0 °Cで 3 0分間撹拌し、 次いで、 4 , 6—ジメ トキシー 2 —メタンスルホ ニルピリ ミ ジン 0. 4 4 gを加え、 5 0 °Cで一晩撹拌した。 反応終了後、 反応液 を氷水に注入し、 酢酸ェチルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去した。 得られた残査をカ ラムクロマ トにて精製し、 目的物 0. 3 4 gを得た。  0.09 g of 60% NaH was suspended in DMF, and a DMF solution of 0.4 g of 2_ (2-methylthiazol-4-yl) phenol was added dropwise at room temperature with stirring. . The mixture was stirred at 30 to 40 ° C for 30 minutes, 0.44 g of 4,6-dimethoxy-2-methanesulfonylpyrimidine was added, and the mixture was stirred at 50 ° C overnight. After the completion of the reaction, the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography to obtain 0.34 g of the desired product.
実施例 1 6 Example 16
2 — ( 2— （ 4， 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フヱニル） ベ ンズォキサゾ一ル （化合物番号 1 1 一 4 ) の合成  Synthesis of 2— (2— (4,6-Dimethoxypyrimidine-1-2-yloxy) phenyl) benzoxazole (Compound No. 11-14)
Figure imgf000046_0002
Figure imgf000046_0002
6 0 %N a H 0. 1 5 gを DMFに懸濁させ、 撹拌下、 室温にて 2— (ベンズ ォキサゾールー 2 _ィル） フエノール 0. 7 gの DMF溶液を滴下した。 3 0〜 4 0。Cで 3 0分間撹拌し、 次いで、 4， 6—ジメ 卜キシ— 2 —メタンスルホニル ピリ ミ ジン 0. 7 gを加え、 5 0 °Cで一晩撹拌した。 反応終了後、 反応液を氷水 P T/JP94/00109 0.15 g of 60% NaH was suspended in DMF, and a DMF solution of 0.7 g of 2- (benzoxazole-2-yl) phenol was added dropwise at room temperature with stirring. 30-40. The mixture was stirred at C for 30 minutes, and then 0.7 g of 4,6-dimethoxy-2-methanesulfonylpyrimidine was added, followed by stirring at 50 ° C overnight. After the reaction is completed, the reaction solution is PT / JP94 / 00109
4 5 に注入し、 酢酸ェチルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水硫 酸マグネシウムで乾燥した後、 溶媒を減圧下留去した。 得られた残査をカラムク 口マ トにて精製し、 目的物 0. 6 2 gを得た。 Injected into 4 and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography to obtain 0.62 g of the desired product.
実施例 1 7 Example 17
2 - ( 2— ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フェニル） ベ ンズチアゾール （化合物番号 2 2 _ 4 ) の合成  Synthesis of 2- (2- (4,6-dimethoxypyrimidine-1-2-yloxy) phenyl) benzthiazole (Compound No. 22_4)
Figure imgf000047_0001
Figure imgf000047_0001
6 0 %N a H 0. 2 gを DMFに懸濁させ、 撹拌下、 室温にて、 2— (ベンズ チアゾール— 2—ィル） フエノール 1. 0 gの DM F溶液を滴下した。 3 0~4 0 °Cで 3 0分間撹拌し、 次いで、 4， 6—ジメ トキシー 2—メタンスルホ二ルビ リ ミ ジン 0. 9 6 gを加え、 6 0 °Cで 5時間、 さらに室温で一晩撹拌した。 反応 終了後、 反応液を氷水に注入し、 ジェチルエーテルで抽出した。 有機層を水及び 飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去し た。 得られた残査をカラムクロマ トにて精製し、 目的物 1. 2 gを得た。  0.2 g of 60% NaH was suspended in DMF, and a solution of 1.0 g of 2- (benzthiazole-2-yl) phenol in 1.0 g of DMF was added dropwise at room temperature with stirring. The mixture was stirred at 30 to 40 ° C for 30 minutes, and then 0.96 g of 4,6-dimethoxy-2-methanesulfonylbilimidine was added, and the mixture was stirred at 60 ° C for 5 hours and further at room temperature. Stirred overnight. After completion of the reaction, the reaction solution was poured into ice water and extracted with getyl ether. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography to obtain 1.2 g of the desired product.
実施例 1 8 Example 18
5— ( 2— （ 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） 一 6— ( 4 , 6—ジメ トキシ ト リアジン一 2—ィルォキシ） フエニル） ォキサゾ一ル （化合物 番号 1 0— 1 2) の合成 5- (2— (4,6-Dimethoxypyrimidine-1-2-yloxy) -1 6— (4,6-Dimethoxytriazine-1-2-yloxy) phenyl) oxazole (Compound No. 10—12) Synthesis of
OMe
Figure imgf000048_0001
炭酸カリウム 0. 1 4 gと 5— （ 2— ( 4 , 6—ジメ トキシピリ ミ ジン一 2 _ ィルォキシ） 一 6—ヒ ドロキシフヱニル） ォキサゾール 0. 1 5 gの DMF溶液 に、 2 _クロロー 4, 6—ジメ トキシ ト リアジン 0. 1 3 gの DM F溶液を一気 に加えた。 反応液を室温で一晩、 撹拌した。 反応終了後、 反応液を氷水に注入し、 酢酸ェチルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシ ゥムで乾燥した後、 溶媒を減圧下留去して、 目的物 0. 2 2 gを得た。 OMe
Figure imgf000048_0001
0.14 g of potassium carbonate and 5— (2— (4,6-dimethoxypyrimidine-12-yloxy) -16-hydroxyphenyl) oxazole 0.15 g of DMF solution of 2-chloro-4,6 —Dimethoxytriazine 0.13 g of DMF solution was added at once. The reaction was stirred at room temperature overnight. After completion of the reaction, the reaction solution was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.22 g of the desired product.
実施例 1 9 Example 19
5 - ( 2— （ 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） 一 6— (N— シクロへキシルカルバモイルォキシ） フヱニル） ォキサゾール （化合物番号 1 3 1 3 2 ) の合成  Synthesis of 5- (2- (4,6-dimethoxypyrimidine-1-2-yloxy) -16- (N-cyclohexylcarbamoyloxy) phenyl) oxazole (Compound No. 131332)
Figure imgf000048_0002
Figure imgf000048_0002
5 - ( 2— ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） 一 6—ヒ ドロ キシフヱニル） ォキサゾール 0. 1 5 gの塩化メチレン溶液にト リェチルァミ ン 0. 0 7 gを加えた。 反応液を室温で撹拌して、 1 5分後にシクロへキシルイソ シァネート 0. 0 8 gを加えた。 さらに、 1. 5時間撹拌後、 反応液に水を加え、 酢酸ェチルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシ ゥムで乾燥した後、 溶媒を減圧下留去して、 得られた油状物を n—へキサンとジ ェチルエーテルの混合溶媒より再結晶して、 目的物 0. 1 7 gを得た。 Triethylamine (0.07 g) was added to a methylene chloride solution of 0.15 g of 5- (2- (4,6-dimethoxypyrimidine-12-yloxy) -16-hydroxyphenyl) oxazole. The reaction was stirred at room temperature and after 15 minutes cyclohexyliso 0.08 g of cyanate was added. After stirring for 1.5 hours, water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the obtained oil was recrystallized from a mixed solvent of n-hexane and diethyl ether. Thus, 0.17 g of the desired product was obtained.
実施例 2 0 Example 20
2 — （ 3 —メチル— 1 , 2 , 4 _ォキサジァゾ一ルー 5—ィル） 一 3 — ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） ピリ ジン （化合物番号 2 6 — 1 4 ) の合成  2 — (3-Methyl-1,2,4_ oxaziazolyl-5-yl)-1-3-(4,6-Dimethoxypyrimidine-1-2-yloxy) pyridine (Compound No. 26-14) Synthesis
Figure imgf000049_0001
Figure imgf000049_0001
3—ヒ ドロキシピコリ ン酸 4. 2 gの DMF溶液に、 Ν， Ν' —カルボニルジ イミダゾール 5. 4 gを加えた。 発熱、 発泡が収まった後に、 ァセトアミ ドキシ ム 2. 4 4 gと トリエチルァミ ン 3. 5 4 gの DM F溶液を加えた。 反応液を室 温で 3時間撹拌して、 さらに 1 2 0 °Cで 2時間反応させた。 反応終了後、 反応液 を氷水に注入し、 1 2 N—塩酸で p Hを？〜 8に調整して、 酢酸ェチルで抽出し た。 有機層を水及び飽和食塩水で洗浄し、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去して、 1. 9 gの 2— ( 3—メチル— 1 , 2， 4 —ォキサジァ ゾール一 5—ィル） 一 3—ヒ ドロキシピリ ジンを得た。  To a solution of 4.2 g of 3-hydroxypicolinic acid in DMF, 5.4 g of Ν, Ν'-carbonyldiimidazole was added. After the exotherm and foaming had subsided, a DMF solution of 2.44 g of acetoamide and 3.54 g of triethylamine was added. The reaction solution was stirred at room temperature for 3 hours, and further reacted at 120 ° C. for 2 hours. After the reaction, pour the reaction mixture into ice water and adjust the pH with 12 N hydrochloric acid. Adjusted to ~ 8 and extracted with ethyl acetate. The organic layer was washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure to obtain 1.9 g of 2- (3-methyl-1, 2,4, -oxaziazole). 5-yl) 1-3-Hydroxypyridin was obtained.
上記ヒ ドロキシピリ ジン 1 gと炭酸カリウム 1. 5 5 gのDMF溶液に、 4， 6 —ジメ トキシ一 2—メタンスルホニルピリ ミ ジン 1. 2 3 gを加え、 5 0 °Cで 2日間撹拌した。 反応溶液に水を加え、 析出した結晶をろ過した。 結晶を酢酸ェ チルに溶かして、 無水硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去して、 目的物 1. 2 gを得た。  To a DMF solution of 1 g of the above hydroxypyridin and 1.55 g of potassium carbonate was added 1.23 g of 4,6-dimethoxy-12-methanesulfonylpyrimidine, and the mixture was stirred at 50 ° C for 2 days. . Water was added to the reaction solution, and the precipitated crystals were filtered. The crystals were dissolved in ethyl acetate, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 1.2 g of the desired product.
実施例 2 1 5 - (2—クロロー 6— (4— ト リフロロメチル一 5， 6—ジヒ ドロフロ 〔2 3 d〕 ピリ ミ ジン— 2—ィルォキシ） フヱニル） ォキサゾール （化合物番号 1 3 8 9 ) の合成 o Example 2 1 Synthesis of 5- (2-chloro-6- (4-trifluoromethyl-1,5,6-dihydrofuro [23d] pyrimidine-2-yloxy) phenyl) oxazole (Compound No. 1389) o
Figure imgf000050_0001
Figure imgf000050_0001
2 - (ォキサゾ一ルー 5 _ィル） 一 3—クロ口フエノール 0. 2 gと炭酸カリ ゥム 0. 4 1 gを DM Fに懸濁させ、 3 0〜 4 0 °Cで 3 0分間撹拌した後、 2— メ タ ンスルホニル一 4— ト リ フロロメチルー 5 , 6—ジヒ ドロフロ 〔2, 3 d〕 ピリ ミ-ジン 0. 2 9 gを加え、 5 0°Cでー晚撹拌した。 反応終了後、 反応液を氷 水に注入し、 酢酸ェチルで抽出した。 有機層を水及び飽和食塩水で洗浄し、 無水 o  2- (Oxazolyl-5_yl) 1-3-Chlorophenol (0.2 g) and potassium carbonate (0.41 g) are suspended in DMF and allowed to stand at 30 to 40 ° C for 30 minutes. After stirring, 0.29 g of 2-methansulfonyl-1-4-trifluoromethyl-5,6-dihydrofuro [2,3d] pyrimidine was added, and the mixture was stirred at 50 ° C. at −50 ° C. After completion of the reaction, the reaction solution was poured into ice water and extracted with ethyl acetate. Wash the organic layer with water and brine, dry
硫酸マグネシウムで乾燥した後、 溶媒を減圧下留去して、 目的物 2 9 gを得 た。 After drying over magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 29 g of the desired product.
実施例 2 2 Example 22
5— ( 2 - ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フヱニル） ォ キサゾール （化合物番号 1 3— 1 ) の合成  Synthesis of 5- (2- (4,6-dimethoxypyrimidine-1-2-yloxy) phenyl) oxazole (Compound No. 13-1)
Figure imgf000050_0002
Figure imgf000050_0002
2— (2 _ホルミルフエノキシ） 一 4, 6—ジメ トキシピリ ミ ジン 0. 5 2 g と p— トルエンスルホニルメチルイソシアニ ド 0. 4 92及び0. 6 9 gの炭酸 カリ ウムを 1 0m lのメタノール中 1 5分間撹拌還流した。 反応液に氷を加え、 析出した固体をろ過した。 固体を酢酸ェチルに溶解し無水硫酸マグネシゥムで乾 燥後、 溶媒を減圧下留去して、 目的物 5 4 gを得た。 実施例 2 3 0.5 m of 2- (2-formylphenoxy) -1,4-dimethoxypyrimidine and 0.492 and 0.69 g of p-toluenesulfonylmethyl isocyanide in 10 m The mixture was stirred and refluxed for 15 minutes in 1 l of methanol. Ice was added to the reaction solution, and the precipitated solid was filtered. The solid was dissolved in ethyl acetate and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 54 g of the desired product. Example 2 3
5— （ 2— （ 4 , 6—ジメ トキシピリ ミ ジン一 2—ィ フェニル） テ トラゾール （化合物番号 1 8— 1 ) の合成  Synthesis of 5- (2— (4,6-dimethoxypyrimidine-1-2-diphenyl) tetrazole (Compound No. 18—1)
Figure imgf000051_0001
Figure imgf000051_0001
2 - (テトラゾールー 5—ィル） フエノール 1. 6 2 gの DM F溶液を、 0. 8 8 gの 6 0 %N a Hの DMF懸濁液中に加えた。 6 0 °Cで 4 0分後に 2. 4 g の 4， 6—ジメ トキシ一 2—メタンスルホニルビリ ミ ジンを加え、 さらに 1時間 反応させた。 反応液を氷にあけて、 酢酸ェチルで抽出した。 有機層を無水硫酸マ グネシゥムで乾燥後、 溶媒を減圧下で留去して、 目的物 2. 5 gを得た。  A solution of 1.62 g of 2- (tetrazol-5-yl) phenol in DMF was added to 0.888 g of a 60% NaH suspension in DMF. After 40 minutes at 60 ° C, 2.4 g of 4,6-dimethoxy-12-methanesulfonylvirimidine was added, and the reaction was further performed for 1 hour. The reaction solution was poured on ice and extracted with ethyl acetate. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 2.5 g of the desired product.
実施例 2 4 Example 2 4
2—メチル一 5— （ 2— ( 4 , 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フエニル） テトラゾール （化合物番号 1 9一 2 ) の合成  Synthesis of 2-methyl-5- (2- (4,6-dimethoxypyrimidine-12-yloxy) phenyl) tetrazole (Compound No. 191-2)
Figure imgf000051_0002
Figure imgf000051_0002
5 - ( 2 - ( 4， 6—ジメ トキシピリ ミ ジン一 2—ィルォキシ） フエニル） テ トラゾール 1. 0 gを DMF 1 5 m 1 に溶解した。 6 0 %N a H 0. 1 5 gを加 え、 5分後にヨウ化メチル 1. 0 8 gを加えた。 室温で 3時間反応させた後、 反 応液に水を加えた。 酢酸ェチルで抽出して、 無水硫酸マグネシウムで乾燥後溶媒 を留去して、 得られた固体をへキサン Zエーテルより再結晶して、 目的物 0. 3 2 gを得た。 実施例 2 5 1.0 g of 5- (2- (4,6-dimethoxypyrimidine-1-2-yloxy) phenyl) tetrazol was dissolved in 15 ml of DMF. 0.15 g of 60% NaH was added, and 5 minutes later, 1.08 g of methyl iodide was added. After reacting at room temperature for 3 hours, water was added to the reaction solution. After extraction with ethyl acetate, drying over anhydrous magnesium sulfate and distilling off the solvent, the obtained solid was recrystallized from hexane Z ether to obtain 0.32 g of the desired product. Example 2 5
4— ( 2 - ( 4 , 6—ジメ トキシピリ ミ ジン _ 2—ィルォキシ） フエニル） ィ ミダゾール （化合物番号 2— 1 ) の合成  Synthesis of 4- (2- (4,6-dimethoxypyrimidine_2-yloxy) phenyl) imidazole (Compound No. 2-1)
NCH NCH
〇〇
Figure imgf000052_0001
Figure imgf000052_0001
1 一べンジルー 5— ( 4 , 6—ジメ トキシピリ ミ ジン _ 2—ィルォキシ） フエ ニル） イ ミダゾ一ル 2 gをエタノール 2 0 m 1 に溶解し、 パラジウム黒 0. ·5 g 及び 1 , 4 ーシクロへキサジェン 4. 1 gを加え、 窒素雰囲気下、 1 0時間加熱 還流した。 反応終了後、 不溶物を濾別し、 溶媒を減圧下留去した。 得られた残査 をカラムクロマ 卜 （シリカゲル ；溶出溶媒 ：塩化メチレン一アセ ト ン = 9 ： 1 ) で精製し、 目的物 0. 8 gを得た。  1 Benzyl 5- (4,6-Dimethoxypyrimidine_2-yloxy) phenyl) imidazole 2 g is dissolved in ethanol 20 m 1, and 0.5 g of palladium black and 1,4 g Then, 4.1 g of -cyclohexadiene was added, and the mixture was refluxed for 10 hours under a nitrogen atmosphere. After completion of the reaction, insolubles were filtered off, and the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography (silica gel; elution solvent: methylene chloride-aceton = 9: 1) to obtain 0.8 g of the desired product.
実施例 2 6 Example 26
2 H - 6 - ( 2 — （4 , 6—ジメ 卜キシピリ ミ ジン一 2—ィルォキシ） フエ二 ル） ピリ ダジン— 3—オン （化合物番号 2 6— 2 4 ) の合成  Synthesis of 2H-6- (2— (4,6-dimethoxypyrimidine-1-2-yloxy) phenyl) pyridazin-3-one (Compound No. 26—24)
Figure imgf000052_0002
Figure imgf000052_0002
2 - ( 2 H—ピリ ダジン一 3—オン一 6 _ィル） フエノール 0. 5 gの DMF 溶液 2 0 m 1 に、 6 0 %N a H 0. 1 1 gを加え、 5 0 で 3 0分間、 撹拌した ( 次いで、 2 —メ タ ンスルホニル一 4 , 6—ジメ トキシピリ ミ ジン 1. 1 6 gを加 え、 室温で 1 4時間撹拌した後、 6 0 °Cで 5時間撹拌した。 反応終了後、 溶媒を 減圧下留去し、 得られた残査を酢酸ェチルー水に溶解し、 有機層を水洗、 次いで 無水硫酸マグネシウムで乾燥した。 濾過後、 溶媒を減圧下留去し、 得られた残査 をカラムクロマ ト （シリカゲル；溶出溶媒：塩化メチレン一アセ ト ン = 9 ： 1 ) で精製し、 目的物 0. 3 gを得た。 2-(2H-pyridazin-3-one-one_6_yl) Phenyl (0.5 g) in DMF solution (20 ml), add 60% NaH 0.1 (1 g), and add 50 The mixture was stirred for 0 minutes ( then, 1.16 g of 2-methansulfonyl-1.4,6-dimethoxypyrimidine was added, and the mixture was stirred at room temperature for 14 hours and then at 60 ° C. for 5 hours). After completion of the reaction, the solvent was distilled off under reduced pressure, the obtained residue was dissolved in ethyl acetate-water, and the organic layer was washed with water. It was dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (silica gel; elution solvent: methylene chloride-aceton = 9: 1) to obtain 0.3 g of the desired product.
上記実施例を含め、 本発明化合物の代表例を以下表 1〜表 3 0に示す。 Representative examples of the compounds of the present invention, including the above Examples, are shown in Tables 1 to 30 below.
第 1 表 Table 1
Figure imgf000054_0001
Figure imgf000054_0001
No. Xn** Ri R2 R3 Yl Y3 Y2 A Z 物性値No. Xn ** Ri R 2 R 3 Yl Y 3 Y 2 AZ Physical properties
1-1 H OMe OMe H H H H CR3 0 1-1 H OMe OMe HHHH CR 30
1-2 6-F OMe OMe H H H H CR3 0 1-2 6-F OMe OMe HHHH CR 30
1-3 6- CI OMe OMe H H H H CR3 0 1-3 6- CI OMe OMe HHHH CR 30
1-4 H OMe OMe H Me H H CR3 0 1.5581-4 H OMe OMe H Me HH CR 3 0 1.558
1-5 6 - CI OMe OMe H Me H H CR3 0 1-5 6-CI OMe OMe H Me HH CR 30
1-6 H OMe OMe H H Me H CR3 0 1-6 H OMe OMe HH Me H CR 3 0
1-7 6-C1 OMe OMe H H Me H CR3 0 1-7 6-C1 OMe OMe HH Me H CR 30
1-8 H OMe OMe H CH2COOH H H CR3 0 1-8 H OMe OMe H CH2COOH HH CR 30
1-9 6 - CI OMe OMe H CH2C00H H H CR3 0 1-9 6-CI OMe OMe H CH 2 C00H HH CR 30
1-10 H OMe OMe H CH2C00Me H H CR3 0 1-10 H OMe OMe H CH 2 C00Me HH CR 30
1-11 6-C1 OMe OMe H CH2C00 e H H CR3 0 1-11 6-C1 OMe OMe H CH 2 C00 e HH CR 30
1-12 H OMe OMe H Py* -（CH)r CR3 0 158-160 物性値は融点 （ ー **) 、 もしく は 2 5 °Cでの屈折率 ** 。 1-12 H OMe OMe H Py *-(CH) r CR 30 158-160 Physical properties are melting point (-**) or refractive index at 25 ° C **.
* P yは 4 , 6—ジメ トキシー 2—ピリ ミ ジルを表す。  * Py represents 4,6-dimethoxy-2-pyrimidyl.
** Hはすべて Hであることを表す。 指定してある場合は、 その他の原子は H であることを表す。 （以下第 2表以降においても同じ。 ） ** H represents H. If specified, the other atoms are H. (The same applies to Table 2 and thereafter.)
Figure imgf000055_0001
Figure imgf000055_0001
No. Xn Ri 2 Rs Y4 Ys Ye A I 物性値-1 ■ H O e OMe H H H H CR3 0 180-181-2 6-F OMe OMe H H H H CR3 0No. Xn Ri 2 Rs Y4 Ys Ye AI Physical property values -1 ■ HO e OMe HHHH CR 30 0 180-181-2 6-F OMe OMe HHHH CR 30
-3 6 - CI OMe OMe H H H H CR3 0-3 6-CI OMe OMe HHHH CR 30
-4 H OMe OMe H Me H H CR3 0-4 H OMe OMe H Me HH CR 30
-5 " 6- CI OMe OMe H Me H H CR3 0-5 "6- CI OMe OMe H Me HH CR 30
-6 H OMe OMe H H Me H CR3 0-6 H OMe OMe HH Me H CR 3 0
-7 6-C1 OMe OMe H CH2Ph H H CR3 0-7 6-C1 OMe OMe H CH 2 Ph HH CR 30
-8 H OMe OMe H H Ph H CR3 0-8 H OMe OMe HH Ph H CR 30
-9 6- CI OMe OMe H CH2COOH H H CR3 0-9 6- CI OMe OMe H CH2COOH HH CR 30
-10 H OMe OMe H CH2COOH H H CR3 0 -10 H OMe OMe H CH2COOH HH CR 30
- 11 6- CI OMe OMe H CH2C00 e H H CR3 0-11 6- CI OMe OMe H CH 2 C00 e HH CR 30
-12 H OMe OMe H CH2C00Me H H CR3 0-12 H OMe OMe H CH 2 C00Me HH CR 30
-13 H OMe OMe H CH2Ph H H CR3 0 1.599-14 H OMe OMe H Tos H H CR3 0-13 H OMe OMe H CH 2 Ph HH CR 3 0 1.599 -14 H OMe OMe H Tos HH CR 30
-15 H OMe OMe H Ac H H CR3 0 -15 H OMe OMe H Ac HH CR 30
Figure imgf000056_0001
Figure imgf000056_0001
No. Xn Ri R2 R3 YT Y8 Yg A Z 物性値-1 H O e OMe H Me H H CR3 0No. Xn Ri R 2 R 3 YT Y 8 Yg AZ Physical property value -1 HO e OMe H Me HH CR 30
-2 6 - CI OMe OMe H Me H H CR3 0-2 6-CI OMe OMe H Me HH CR 30
-3 6-F OMe OMe H Me H H CR3 0-3 6-F OMe OMe H Me HH CR 30
-4 H OMe OMe H CH2Ph- CI. -4 H H CR3 0-4 H OMe OMe H CH 2 Ph- CI. -4 HH CR 30
-5 6 - CI OMe OMe H CH2Ph-Cl- -4 H H CR3 0-5 6-CI OMe OMe H CH 2 Ph-Cl- -4 HH CR 30
-6 6-F OMe OMe H CH2Ph-Cl- -4 H H CR3 0-6 6-F OMe OMe H CH 2 Ph-Cl- -4 HH CR 30
-7 H OMe OMe H CH2C00H H H CR3 0-7 H OMe OMe H CH 2 C00H HH CR 30
-8 6 - CI OMe OMe H CH2C00H H H CR3 0-8 6-CI OMe OMe H CH 2 C00H HH CR 30
-9 6-F OMe OMe H CH2C00H H H CR3 0-9 6-F OMe OMe H CH 2 C00H HH CR 30
-10 H OMe OMe H CH2C00Me H H CR3 0-10 H OMe OMe H CH 2 C00Me HH CR 30
-11 6 - CI OMe OMe H CH2C00Me H H CR3 0-11 6-CI OMe OMe H CH 2 C00Me HH CR 30
-12 6-F OMe OMe H CH2C00Me H H CR3 0-12 6-F OMe OMe H CH 2 C00Me HH CR 30
-13 H OMe OMe H CH2Ph H H CR3 0-13 H OMe OMe H CH 2 Ph HH CR 30
-14 6- CI OMe OMe H CH2Ph H H CR3 0-14 6- CI OMe OMe H CH 2 Ph HH CR 30
-15 6-F OMe OMe H CH2Ph H H CR3 0 第 4 表 -15 6-F OMe OMe H CH 2 Ph HH CR 30 Table 4
Figure imgf000057_0001
Figure imgf000057_0001
D  D
ί υ. ΛΙΙ K 2 Λ 3 v A 7 ί υ. ΛΙΙ K 2 Λ 3 v A 7
n L 物性値-1 6-Br OMe OMe H H CR3 0n L Physical properties -1 6-Br OMe OMe HH CR 30
-2 6 - C I O e OMe H H CR3 0-2 6-CIO e OMe HH CR 30
-3 6-F OMe OMe H H CR3 0-3 6-F OMe OMe HH CR 30
-4 6- 1 OMe OMe H H CR3 0-4 6- 1 OMe OMe HH CR 30
-5 6-OPh OMe OMe H H CR3 0-5 6-OPh OMe OMe HH CR 30
-6 H OMe -OCH2 CH2 - H CR3 0-6 H OMe -OCH 2 CH 2 -H CR 30
-7 H OMe CF3 H H CR3 0-7 H OMe CF 3 HH CR 30
-8 H OMe Me H H CR3 0-8 H OMe Me HH CR 30
-9 H Me Me H H CR3 0-9 H Me Me HH CR 30
-10 H OMe NHMe H H CR3 0-10 H OMe NHMe HH CR 30
-11 H OMe Me 2 H H CR3 0-11 H OMe Me 2 HH CR 30
-12 H OMe OMe H H CR3 0 115-117-13 H OMe OPr- i H H CR3 0-12 H OMe OMe HH CR 3 0 115-117-13 H OMe OPr- i HH CR 30
-14 H OMe SMe H H CR3 0-14 H OMe SMe HH CR 30
-15 H Me SMe H H CR3 0-15 H Me SMe HH CR 30
-16 H OMe OMe H Me CR3 0-16 H OMe OMe H Me CR 30
-17 6-C 1 OMe OMe H Me CR3 0-17 6-C 1 OMe OMe H Me CR 30
-18 6-F OMe OMe H Me CR3 0-18 6-F OMe OMe H Me CR 30
-19 6-OPh OMe OMe H Me CR3 0-19 6-OPh OMe OMe H Me CR 30
-20 H OMe OMe H Ph CR3 0-20 H OMe OMe H Ph CR 30
-21 6-C 1 OMe OMe H Ph CR3 0-21 6-C 1 OMe OMe H Ph CR 30
-22 6-F OMe OMe H Ph CR3 0 -22 6-F OMe OMe H Ph CR 30
- 23 H OMe OMe H COOH CR3 0-23 H OMe OMe H COOH CR 30
-24 H OMe OMe H COOMe CR3 0-24 H OMe OMe H COOMe CR 30
-25 6- C I OMe OMe H COOMe CR3 0-25 6- CI OMe OMe H COOMe CR 30
-26 6-F OMe OMe H COOMe CR3 0 -26 6-F OMe OMe H COOMe CR 30
Ri
Figure imgf000058_0001
Ri
Figure imgf000058_0001
No. Xn Ri R2 R3 Yll Yl z A Z 物性値-1 6-Br OMe OMe H H H CR3 0No. Xn Ri R 2 R 3 Yll Y lz AZ Physical property value -1 6-Br OMe OMe HHH CR 30
-2 6-C1 OMe OMe H H H CR3 0-2 6-C1 OMe OMe HHH CR 30
-3 6-F OMe OMe H H H CR3 0-3 6-F OMe OMe HHH CR 30
-4 H OMe - 0CH2CH2- COOH H CR3 0-4 H OMe-0CH 2 CH 2 -COOH H CR 30
-5 H OMe -0CH2CH2- COOMe H CR3 0-5 H OMe -0CH 2 CH 2 -COOMe H CR 30
-6 H OMe -0CH2CH2- H H CR3 0-6 H OMe -0CH 2 CH 2 -HH CR 30
-7 H OMe -0CH2CH2- Me H CR3 0-7 H OMe -0CH 2 CH 2 -Me H CR 30
-8 H OMe -0CH2CH2- Ph H CR3 0-8 H OMe -0CH 2 CH 2 -Ph H CR 30
-9 H OMe O e H COOH H CR3 0-9 H OMe O e H COOH H CR 30
-10 H OMe OMe H COOMe H CR3 0-10 H OMe OMe H COOMe H CR 3 0
-11 H OMe OMe H H H CR3 0-11 H OMe OMe HHH CR 30
-12 H OMe OMe H H H CR3 0 Gum-13 H OMe OMe H H H CR3 0-12 H OMe OMe HHH CR 30 Gum-13 H OMe OMe HHH CR 30
-14 H OMe OMe H Me H CR3 0-14 H OMe OMe H Me H CR 30
-15 H OMe OMe H Ph H CR3 0-15 H OMe OMe H Ph H CR 30
-16 6-1 OMe OMe H H H CR3 0-16 6-1 OMe OMe HHH CR 30
-17 6-OMe OMe OMe H H H CR3 0 -17 6-OMe OMe OMe HHH CR 30
Figure imgf000059_0001
Figure imgf000059_0001
No. Xn Ri R2 Rs Yl 3 Yl 4 A Z 物性値-1 H OMe OMe H H COOH CR3 0No. Xn Ri R2 Rs Yl 3 Yl 4 AZ Physical property value -1 H OMe OMe HH COOH CR 30
-2 H O e OMe H H COOMe CR3 0-2 HO e OMe HH COOMe CR 30
-3 H OMe OMe H H H CR3 0 Gum-4 H OMe OMe H H Me CR3 0-3 H OMe OMe HHH CR 30 Gum-4 H OMe OMe HH Me CR 30
-5 H OMe OMe H H Ph CR3 0-5 H OMe OMe HH Ph CR 30
-6 6-F CF3 -OCH2CH2- H H CR3 0-6 6-F CF 3 -OCH2CH2- HH CR 30
-7 6 - CI CF3 -OCH2CH2- H H CR3 0-7 6-CI CF 3 -OCH2CH2- HH CR 30
-8 6- Br CF3 -0CH2CH2- H H CR3 0-8 6- Br CF 3 -0CH 2 CH 2 -HH CR 30
-9 6-1 CF3 -0CH2CH2- H H CR3 0-9 6-1 CF 3 -0CH 2 CH 2 -HH CR 30
-10 6-F OMe OMe H H H CR3 0-10 6-F OMe OMe HHH CR 30
-11 6- CI OMe OMe H H H CR3 0-11 6- CI OMe OMe HHH CR 30
-12 6 - Br OMe OMe H H H CR3 0-12 6-Br OMe OMe HHH CR 30
-13 6-1 OMe OMe H H H CR3 0-13 6-1 OMe OMe HHH CR 30
-14 H OMe -OCH2CH2- H COOH CR3 0 -14 H OMe -OCH2CH2- H COOH CR 30
- 15 H OMe -OCH2CH2- H COOMe CR3 0-15 H OMe -OCH2CH2- H COOMe CR 30
-16 H OMe -0CH2CH2- H H CR3 0-16 H OMe -0CH 2 CH 2 -HH CR 30
-17 H CF3 -OCH2CH2- H H CR3 0-17 H CF 3 -OCH2CH2- HH CR 30
-18 H OMe - 0CH2CH2- H Me CR3 0 -18 H OMe-0CH 2 CH 2 -H Me CR 30
- 19 H OMe OMe H H Me CR3 0-19 H OMe OMe HH Me CR 30
-20 H OMe H Ph CR3 0 -20 H OMe H Ph CR 30
0 εΗ0 lid Η Η 3Η0 3W0 Η 9ΐ-Ι0 ε Η0 lid Η Η 3Η0 3W0 Η 9ΐ-Ι
0 εΗ3 Η Η 3 0 Η η-ι0 ε Η3 Η Η 3 0 η η-ι
0 εΗ3 Η Η Η 8W0 Η εΐ -丄0 ε Η3 Η Η Η 8W0 Η εΐ-丄
0 εΗ3 Η -2Η0ζΗ00- 9W0 Η ζι-ι0 ε Η3 Η- 2 Η0 ζ Η00- 9W0 Η ζι-ι
0 εΗ3 Η -5Η3ΖΗ30- 9W0 Η π-ι0 ε Η3 Η- 5 Η3 Ζ Η30- 9W0 Η π-ι
0 εΗ3 Η Η -SH3SH30- εί13 Η ΟΙ-ί0 ε Η3 Η Η- S H3 S H30- ε ί13 ΟΙ ΟΙ-ί
0 εΗ3 Η Η d - 9 6-10 ε Η3 Η Η d-9 6-1
0 SH0 Η Η Η ίΙ-9 2-L0 S H0 Η Η Η ίΙ-9 2-L
0 εϋ3 Η -3Η3ΖΗ30- ά-9 L-L0 ε ϋ3 Η- 3 Η3 Ζ Η30- ά-9 LL
0 εΗ0 Η -ΖΗ3ΖΗ30- ά-9 9-丄0 ε Η0 Η- Ζ Η3 Ζ Η30- ά-9 9- 丄
0 εΗ0 Η Η -ζΗ32Η0Ο- 8dO ά-9 - 9-10 ε Η0 Η Η- ζ Η3 2 Η0Ο- 8 dO ά-9-9-1
0 εΗ0 aw Η Η 13-9 ト丄0 ε Η0 aw Η Η 13-9 ton
0 εΗ0 Η Η Η 13-9 -L0 ε Η0 Η Η Η 13-9 -L
0 εΗ3 Η -2Η33Η30- 13-9 Z-L0 ε Η3 Η- 2 Η3 3 Η30-13-9 ZL
0 εΗ3 Η Η -ΖΗ32Η00- Ϊ3-9 ί -丄 厨舅 z V 91入 9 ΙΑ 'ON 0 ε Η3 Η Η - Ζ Η3 2 Η00- Ϊ3-9 ί -丄Kuriyashuto z V 91 input 9 iota Alpha 'ON
Figure imgf000060_0001
Figure imgf000060_0001
8 S  8 S
60I00/^6dT/XDd 6S0Lllt6 OM 第 8 表 60I00 / ^ 6dT / XDd 6S0Lllt6 OM Table 8
Figure imgf000061_0001
Figure imgf000061_0001
No. Xn R, R2 R Y, 7 A 1 物性値 No. Xn R, R 2 RY, 7 A 1 Physical properties
113-115
Figure imgf000061_0002
113-115
Figure imgf000061_0002
8-21 H OMe OMe H H Ν 0  8-21 H OMe OMe H H Ν 0
8-22 H OMe OMe H H Ν s  8-22 H OMe OMe H H Ν s
8-23 6- CI OMe OMe H H Ν 0  8-23 6- CI OMe OMe H H Ν 0
8-24 6 - CI OMe OMe H H Ν s  8-24 6-CI OMe OMe H H Ν s
8-25 H OMe -OCH2CH2- H CR3 0 8-25 H OMe -OCH2CH2- H CR 30
8-26 H OMe -OCH2CH2- Me CR3 0 8-26 H OMe -OCH2CH2-Me CR 30
8-27 H OMe -0CH2CH2- 3-NO2-PI1 CR3 0 8-27 H OMe -0CH 2 CH 2 - 3-NO2-PI1 CR 3 0
8-28 H OMe -OCH2CH2- H CRg s  8-28 H OMe -OCH2CH2- H CRg s
8-29 H OMe - 0CH2CH2 - Me CR3 s 8-29 H OMe-0CH 2 CH 2 -Me CR 3 s
8-30 H OMe -OCH2CH2- 3-NO2-PI1 CR3 s 8-30 H OMe -OCH2CH2- 3-NO2-PI1 CR 3 s
8-31 6-C1 OMe -0CH2CH2- H CR3 s 8-31 6-C1 OMe -0CH 2 CH 2 -H CR 3 s
8-32 6- CI OMe -0CHzCH2- Me CR3 0 8-32 6- CI OMe -0CH z CH 2 -Me CR 30
8-33 6- CI OMe -OCH2CH2- 3-N02-Ph CR3 s 8-33 6- CI OMe -OCH2CH2- 3-N0 2 -Ph CR 3 s
8-34 H OMe OMe H CH2S e CR3 0 64-658-34 H OMe OMe H CH 2 S e CR 3 0 64-65
8-35 H OMe OMe H CH2S02 e CR3 0 160-1628-35 H OMe OMe H CH 2 S0 2 e CR 3 0 160-162
8-36 6 - Br OMe OMe H Me CR3 0 8-36 6-Br OMe OMe H Me CR 3 0
8-37 6-1 OMe OMe H Me CR3 0 8-37 6-1 OMe OMe H Me CR 3 0
8-38 6-OPh OMe OMe H Me CR3 0 8-38 6-OPh OMe OMe H Me CR 30
Figure imgf000062_0001
Figure imgf000062_0001
No. Xn R, R2 R3 Y18 A Z 物性値No. Xn R, R 2 R 3 Y 18 AZ Physical properties
Q_ U U U Q_ U U U
y 丄 Π uiwe U G n Π n y 丄 Π uiwe U G n Π n
し U  U
Q_9 u u  Q_9 u u
o r uiwe uivie fl n n  o r uiwe uivie fl n n
し U  U
u u  u u
y 0 し丄 UMc UMc n n し 1 n u y 0 丄 UMc UMc n n 1 1 n u
u  u
Π UMc UlVlc Π n  Π UMc UlVlc Π n
し K3 u  Then K3 u
o n  o n
0 门 UMc UMc Π Me ΓしΡ u 0 门 UMc UMc Π Me Γ Ρ u
Ρ n  Ρ n
U し J Π UΜMc UMc Π ΓしΡ u U J J Π UΜMc UMc Π Γ Ρ u
0 u Ph n 0 u Ph n
し u  Then u
0 D し丄 UlVlc Π UMΜΡc u Π P i lhl n  0 D 丄 UlVlc Π UMΜΡc u Π P i lhl n
し u  Then u
Q Q u  Q Q u
y_ y n UlVlc uiwe Π n y_ y n UlVlc uiwe Π n
6, 1： し i 2 r n し U  6, 1: i 2 r n then U
9-10 H OMe OMe H H CR3 s 9-10 H OMe OMe HH CR 3 s
9-11 6 - CI OMe OMe H H CR3 s 9-11 6-CI OMe OMe HH CR 3 s
9-12 H OMe OMe H Me CR3 s 9-12 H OMe OMe H Me CR 3 s
9-13 6 - CI OMe OMe H Me CR3 s 9-13 6-CI OMe OMe H Me CR 3 s
9-14 H OMe -0CH2CH2- H CR3 0 9-14 H OMe -0CH 2 CH 2 -H CR 30
9-15 H OMe -OCH2CH2- Me CR3 0 9-15 H OMe -OCH2CH2-Me CR 30
9 - 16 H OMe -OCH2CH2- 3-N02-Ph CR3 0 9 - 16 H OMe -OCH2CH2- 3- N0 2 -Ph CR 3 0
9-17 H OMe -0CH2CH2- H CR3 s 9-17 H OMe -0CH 2 CH 2 -H CR 3 s
9-18 H OMe -OCH2CH2- Me CR3 s 9-18 H OMe -OCH2CH2-Me CR 3 s
9-19 H OMe -OCH2CH2- 3-N02-Ph CR3 s 9-19 H OMe -OCH2CH2- 3-N0 2 -Ph CR 3 s
9-20 6-C1 OMe -0CH2CH2- H CR3 s 9-20 6-C1 OMe -0CH 2 CH 2 -H CR 3 s
9-21 6- CI OMe -OCH2CH2- Me CR3 0 9-21 6- CI OMe -OCH2CH2-Me CR 30
9-22 6- CI OMe -0CH2CH2- 3-NO2-PI1 CR3 s 9-22 6- CI OMe -0CH 2 CH 2 - 3-NO2-PI1 CR 3 s
9-23 6 - CI OMe -OCH2CH2- 4-MeO-Ph CR3 0 9-23 6-CI OMe -OCH2CH2- 4-MeO-Ph CR 30
9-24 6- CI OMe -OCH2CH2- 4-MeS-Ph CR3 0 9-24 6- CI OMe -OCH2CH2- 4-MeS-Ph CR 30
9-25 6-F OMe OMe H Me CR3 0 1069-25 6-F OMe OMe H Me CR 3 0 106
9-26 6-F OMe OMe H CF3 CR3 0 9-26 6-F OMe OMe H CF 3 CR 30
9-27 6- Br OMe OMe H CF3 CR3 0 9-27 6- Br OMe OMe H CF 3 CR 30
9-28 6-1 OMe OMe H CF3 CR3 0
Figure imgf000063_0001
9-28 6-1 OMe OMe H CF 3 CR 3 0
Figure imgf000063_0001
I I
第 11 表 Table 11
Figure imgf000064_0001
Figure imgf000064_0001
No. Xn R. R2 Ra Yl 9 Y20 A Z 物性値No. Xn R. R 2 Ra Yl 9 Y20 AZ Physical properties
LI- 1 H OMe OMe H H H CR3 0 LI- 1 H OMe OMe HHH CR 30
LI- 2 6-F OMe OMe H H H CR3 0 LI- 26-F OMe OMe HHH CR 30
LI- 3 6-C1 OMe OMe H H H CR3 0 LI- 36-C1 OMe OMe HHH CR 30
LI - 4 H OMe OMe H -（CH)4 CR3 0 88-90LI-4 H OMe OMe H-(CH) 4 CR 3 0 88-90
Ll-5 H OMe OMe H H H CR3 s Ll-5 H OMe OMe HHH CR 3 s
d-6 H OMe OMe H H Me CR3 0 d-6 H OMe OMe HH Me CR 30
Ll-7 H OMe OMe H H Ph CR3 0 Ll-7 H OMe OMe HH Ph CR 30
.1-8 6-F OMe OMe H CF3 H CR3 0 .1-8 6-F OMe OMe H CF 3 H CR 30
.1-9 H OMe OMe H Me H CR3 0 1.528.1-9 H OMe OMe H Me H CR 3 0 1.528
.1-10 H OMe OMe H Et H CR3 0 .1-10 H OMe OMe H Et H CR 30
.1-11 H OMe OMe H Ph H CR3 0 .1-11 H OMe OMe H Ph H CR 30
.1-12 6-F OMe OMe H Me Me CR3 0 .1-12 6-F OMe OMe H Me Me CR 30
.1-13 H OMe OMe H Me Me CR3 0 .1-13 H OMe OMe H Me Me CR 30
.1-14 H OMe OMe H Et Me CR3 0 .1-14 H OMe OMe H Et Me CR 30
.1-15 H OMe OMe H Ph Me CR3 0 .1-15 H OMe OMe H Ph Me CR 30
.1-16 6- CI OMe OMe H Me Me CR3 0 .1-16 6- CI OMe OMe H Me Me CR 30
.1-17 6-Br OMe OMe H Me Me CR3 0 .1-17 6-Br OMe OMe H Me Me CR 30
.1-18 6-1 OMe OMe H Me Me CR3 0 第 12 表 .1-18 6-1 OMe OMe H Me Me CR 30 Table 12
Figure imgf000065_0001
Figure imgf000065_0001
No. Xn Ri R2 R3 Y21 Y22 A Z 物性値-1 6-F O e OMe H Me COOH CR3 0No. Xn Ri R 2 R 3 Y21 Y22 AZ Physical property value -1 6-FO e OMe H Me COOH CR 30
-2 6-F OMe OMe H Me COOMe CR3 0-2 6-F OMe OMe H Me COOMe CR 30
-3 6-F OMe OMe H Me Et CR3 0-3 6-F OMe OMe H Me Et CR 30
-4 6-C1 OMe OMe H H H CR3 S-4 6-C1 OMe OMe HHH CR 3 S
-5 6-F OMe OMe H H H CR3 0-5 6-F OMe OMe HHH CR 30
-6 H OMe OMe H H H CR3 0-6 H OMe OMe HHH CR 30
-7 H OMe OMe H Me H CR3 0-7 H OMe OMe H Me H CR 30
-8 6- CI OMe OMe H Ph H CR3 0-8 6- CI OMe OMe H Ph H CR 30
-9 6-F OMe OMe H Ph H CR3 0 1.594-10 6-1 OMe OMe H Ph H CR3 0-9 6-F OMe OMe H Ph H CR 30 0 1.594-10 6-1 OMe OMe H Ph H CR 30
-11 6-F OMe OMe H Me Me CR3 0-11 6-F OMe OMe H Me Me CR 30
-12 6-F OMe OMe H Me Ph CR3 0-12 6-F OMe OMe H Me Ph CR 30
-13 H OMe OMe H Me Me CR3 0-13 H OMe OMe H Me Me CR 3 0
-14 6-C1 OMe OMe H Me Me CR3 0-14 6-C1 OMe OMe H Me Me CR 30
-15 H OMe OMe H Ph Me CR3 0 -15 H OMe OMe H Ph Me CR 30
Figure imgf000066_0001
Figure imgf000066_0001
No. Xn R2 R3 A Y2 Y24 Z 物性値
Figure imgf000066_0002
n U ΌΌ ΌΙ u n No. Xn R 2 R 3 A Y2 Y 24 Z Physical properties
Figure imgf000066_0002
n U ΌΙ ΌΙ un
13-2 H し i し 1 n し U  13-2 H then i then 1 n then U
13-3 H n Upしr u n Urしrト u u u u n  13-3 H n Up and r u n Ur and r u u u u n
し U u ェ  U u
Id - 4 H Me OMe u n  Id-4 H Me OMe un
し u  Then u
Id - 5 M6 OMe CO  Id-5 M6 OMe CO
し 0 r  Then 0 r
1 q U PR u u  1 q U PR u u
丄 Γ OMe n u Me Γ OMe n u
1 Q-7 u OMe H 11 PR 0 H H 11 c 0 1 Q-7 u OMe H 11 PR 0 HH 11 c 0
10  Ten
0 u Π ρ OMe H H pnflF† n u  0 u ρ ρ OMe H H pnflF † n u
1 u  1 u
丄 nup OMe H 11 11 n 1R4 -丄 nup OMe H 11 11 n 1R4-
1 1
丄 q_i 丄 q_i
ΰ 丄 U Π OMe li u n u n 丄 1 <93— 11 Π OMe M n π n u  ΰ 丄 U Π OMe li u n u n 丄 1 <93-- 11 Π OMe M n π n u
13-12 H OMe OMe H CRs H COOMe 0 91-93 13-12 H OMe OMe H CRs H COOMe 0 91-93
13-13 H O e OMe H CR3 H p-Tos 0 136-13813-13 HO e OMe H CR 3 H p-Tos 0 136-138
13-14 H OMe OMe H CR3 H COOPr-i 0 111-11313-14 H OMe OMe H CR 3 H COOPr-i 0 111-113
13-15 H OMe OMe H CR3 Me H 0 13-15 H OMe OMe H CR 3 Me H 0
13-16 H OMe OMe H CR3 H Me 0 13-16 H OMe OMe H CR 3 H Me 0
13-17 H OMe OMe H CR3 Me Me 0 13-17 H OMe OMe H CR 3 Me Me 0
13-18 H OMe -0CH2CH2 CR3 H H 0 13-18 H OMe -0CH 2 CH 2 CR 3 HH 0
13-19 H OMe CR3 H H s 13-19 H OMe CR 3 HH s
13-20 H Me -0CH2CH2 CR3 H H 0 13-20 H Me -0CH 2 CH 2 CR 3 HH 0
13-21 H Me CR3 H H s 13-21 H Me CR 3 HH s
13-22 H CF3 -0CH2CH2 CRs H H 0 13-22 H CF 3 -0CH 2 CH 2 CRs HH 0
13-23 H CF3 CR3 H H s13-23 H CF 3 CR 3 HH s
13-24 H OMe OMe H CR3 H H s 13-24 H OMe OMe H CR 3 HH s
13-25 *1 OMe OMe H CR3 H H 0 130-13213-25 * 1 OMe OMe H CR 3 HH 0 130-132
13-26 2-C1-4-C1 OMe OMe H CR3 H H 0 101-10413-26 2-C1-4-C1 OMe OMe H CR 3 HH 0 101-104
13-27 3 - CI OMe OMe H CRs H H 0 125-127 P / 109 13-27 3-CI OMe OMe H CRs HH 0 125-127 P / 109
6 5 第 13 (つづき） 6 5 13th (continued)
No. Xn Ri R2 R3 A Y2 Y24 Z 物性値-28 3-F Me OMe H CR3 H H sNo. Xn Ri R 2 R 3 A Y2 Y 2 4 Z Physical properties -28 3-F Me OMe H CR 3 HH s
-29 3-F OMe OMe H CR3 H H 0 141-142-30 3-Me-4-0Me OMe OMe H CR3 H H 0 147-150-31 3-OMe Me OMe H CR3 H H 0-29 3-F OMe OMe H CR 3 HH 0 141-142-30 3-Me-4-0Me OMe OMe H CR 3 HH 0 147-150-31 3-OMe Me OMe H CR 3 HH 0
-32 3-OMe CF3 OMe H CR3 H H 0-32 3-OMe CF 3 OMe H CR 3 HH 0
-33 3-OMe OMe OMe H CR3 H H 0 148-149-34 4-C1 OMe OMe H CR3 H H 0 125-128-35 4-C卜 5 - Me OMe OMe H CR3 H H 0 158-160-36 4 - C卜 6 - CI OMe -OCH2CH2一 CR3 H H 0-33 3-OMe OMe OMe H CR 3 HH 0 148-149-34 4-C1 OMe OMe H CR 3 HH 0 125-128-35 4-C 5-Me OMe OMe H CR 3 HH 0 158-160- 36 4-C 6-CI OMe -OCH 2 CH 2 1 CR 3 HH 0
-37 4-C00Me OMe OMe H CR3 H H 0 172-38 4-Me-5-Me OMe OMe H CR3 H H 0 115-116 - 39 4-OMe Me OMe H CR3 H H 0-37 4-C00Me OMe OMe H CR 3 HH 0 172-38 4-Me-5-Me OMe OMe H CR 3 HH 0 115-116 - 39 4-OMe Me OMe H CR 3 HH 0
-40 4-OMe CF3 OMe H CR3 H H 0-40 4-OMe CF 3 OMe H CR 3 HH 0
-41 4-OMe OMe OMe H CR3 H H 0 92-94-42 4-OMe OMe -0CH2CH2 ― CR., H H 0-41 4-OMe OMe OMe H CR 3 HH 0 92-94-42 4-OMe OMe -0CH 2 CH 2 ― CR., HH 0
-43 5-C1 OMe OMe H CR3 H H 0 151-152-44 5-Et OMe OMe H CR3 H H 0 87-89-45 5-i-Pr OMe OMe H CR3 H H 0 1.425-46 5-Me OMe OMe H CR3 H H 0 115-116-47 5-Me-6-Cl OMe OMe H CR3 H H 0 95-97-48 5-Me-6-Me OMe OMe H CR3 H H 0 92-94-49 5-OMe Me OMe H CR3 H H 0-43 5-C1 OMe OMe H CR 3 HH 0 151-152-44 5-Et OMe OMe H CR 3 HH 0 87-89-45 5-i-Pr OMe OMe H CR 3 HH 0 1.425-46 5-Me OMe OMe H CR 3 HH 0 115-116-47 5-Me-6-Cl OMe OMe H CR 3 HH 0 95-97-48 5-Me-6-Me OMe OMe H CR 3 HH 0 92-94-49 5-OMe Me OMe H CR 3 HH 0
-50 5-OMe CF3 OMe H CR3 H H 0-50 5-OMe CF 3 OMe H CR 3 HH 0
-51 5-OMe OMe OMe H CR3 H H 0 123-125-52 5-t-Bu OMe OMe H CR3 H H 0 Cum-53 6- (3， 5-Dimet oxybenzoy loxy) OMe OMe H CR3 H H 0 139-140-54 6- (3， 5-Dimethoxybenzyloxy) OMe OMe H CR3 H H 0 130-131-55 6-(4-chlorobenzoyloxy) OMe OMe H CR3 H H 0-51 5-OMe OMe OMe H CR 3 HH 0 123-125-52 5-t-Bu OMe OMe H CR 3 HH 0 Cum-53 6- (3,5-Dimet oxybenzoy loxy) OMe OMe H CR 3 HH 0 139-140-54 6- (3,5-Dimethoxybenzyloxy) OMe OMe H CR 3 HH 0 130-131-55 6- (4-chlorobenzoyloxy) OMe OMe H CR 3 HH 0
-56 6-Br OMe OMe H CR3 H H 0 117-120-57 6 - Br OMe OMe H CR3 H Me 0-56 6-Br OMe OMe H CR 3 HH 0 117-120-57 6-Br OMe OMe H CR 3 H Me 0
-58 6-Br OMe OMe H CR3 Me H 0-58 6-Br OMe OMe H CR 3 Me H 0
-59 6-Br OMe OMe H CR3 Me Me 0-59 6-Br OMe OMe H CR 3 Me Me 0
-60 6-CF3 OMe OMe H CR3 H H 0 100-102-61 6 - CF3 OMe OMe H CR3 H H s 2： -60 6-CF 3 OMe OMe H CR 3 HH 0 100 -102 -61 6-CF 3 OMe OMe H CR 3 HH s 2:
ェ ェYe
Figure imgf000068_0001
Figure imgf000068_0001
9 9
6 7 第 13 (つづき） 6 7 13th (continued)
No. Xn R , R2 R3 A Z 物性値3-95 6-F OMe OMe H CR3 H H 0 77-783-96 6-F OMe OMe H CR3 H H S No. Xn R, R 2 R 3 AZ physical properties 3-95 6-F OMe OMe H CR 3 HH 0 77-783-96 6-F OMe OMe H CR 3 HHS
3-97 6-F Me OMe H CR3 H H 03-97 6-F Me OMe H CR 3 HH 0
3-98 6-F Me OMe H CR3 H H S3-98 6-F Me OMe H CR 3 HHS
3-99 6-F CF3 OMe H CR3 H H 03-99 6-F CF 3 OMe H CR 3 HH 0
3-100 6-F CF3 OMe H CR3 H H s3-100 6-F CF 3 OMe H CR 3 HH s
3-101 -F OMe OMe H CR3 H Me 0 1. 474 u OMe H 3 Up u n u 3-101 -F OMe OMe H CR 3 H Me 0 1.474 u OMe H 3 Up unu
OMe Mp  OMe Mp
3 n
Figure imgf000069_0001
3 n
Figure imgf000069_0001
ΰ VJU fi u - Mp -0CH; 3 H n u ΰ VJU fi u-Mp -0CH ; 3 H nu
Q 07 u r Mp -0CH; C Q 07 ur Mp -0CH ; C
Π 2 H  Π 2 H
fi - F -OCH; CR3 H H 0fi-F -OCH; CR 3 HH 0
£7 6-F 3 -0CH2CH2 CR3 H H s £ 7 6-F 3 -0CH 2 CH 2 CR 3 HH s
ϋ fi - 1 OMe H 3 H H n 128 - 130 3 - 1 1 1 u OMe OMe H 3 H Me n i Qj OMe OMe H CR3 Me H 0ϋ fi-1 OMe H 3 HH n 128-130 3-1 1 1 u OMe OMe H 3 H Me ni Qj OMe OMe H CR 3 Me H 0
3-113 G- 1 OMe OMe H CR3 Me Me 03-113 G- 1 OMe OMe H CR 3 Me Me 0
3-114 6- j -Pr OMe OMe H CR3 H H 03-114 6- j -Pr OMe OMe H CR 3 HH 0
3 - 1 15 d 6- e OMe OMe H CR3 H H 0 125-128 u -Mp OMe OMe H CR3 H H s3-1 15 d 6- e OMe OMe H CR 3 HH 0 125-128 u -Mp OMe OMe H CR 3 HH s
-4- OMe 0 96-99  -4- OMe 0 96-99
OMe OMe H CR3 H H 0 95-973-119 6-N02 OMe OMe u H H 0 144-1463- 120 6-N02 U e OMe H u u c OMe OMe H CR 3 HH 0 95-973-119 6-N0 2 OMe OMe u HH 0 144-1463- 120 6-N0 2 U e OMe H uuc
CR 3 CR 3
3-121 6-OAc OMe OMe H CR3 H H 0 Gum3-122 6-OAl l yl OMe OMe H CR3 H H 0 1. 5723-123 6-OBn OMe OMe H CR3 H H 0 137-1383-124 6-0C3H6C00Et OMe OMe H CR3 H H 0 1. 5513-125 6-0C 3H6C00H OMe OMe H CRS H H 0 159-1603-126 OMe OMe H CR3 H H 0 1. 5323-127 6-0CH2C00Et OMe OMe H CR3 H H 0 95-97 9-H3=H3-H0=H0-S :ΐ*3-121 6-OAc OMe OMe H CR 3 HH 0 Gum3-122 6-OAllyl OMe OMe H CR 3 HH 0 1. 5723-123 6-OBn OMe OMe H CR 3 HH 0 137-1383-124 6- 0C 3 H 6 C00Et OMe OMe H CR 3 HH 0 1.555-125 6-0C 3 H 6 C00H OMe OMe H CR S HH 0 159-1603-126 OMe OMe H CR 3 HH 0 1. 5323-127 6- 0CH 2 C00Et OMe OMe H CR 3 HH 0 95-97 9-H3 = H3-H0 = H0-S: ΐ *
S8-6i s 13000 H H 删 H 09ΐ-δΐS8-6i s 13000 H H 删 H 09ΐ-δΐ
0 aw 4d 6ao H 删 H 69Ϊ-2Ι s H H εΏ H 9W0 na-l-9 8ST-ST s H H εΏ H UdS-9 AST-SI0 aw 4d 6 ao H 删 H 69Ϊ-2Ι s HH ε Ώ H 9W0 na-l-9 8ST-ST s HH ε Ώ H UdS-9 AST-SI
0 H H εΏ H o ildS-9 991-εΐ s H H £Ώ H dOS-9 SST-8T0 HH ε Ώ H o ildS-9 991-εΐ s HH £ Ώ H dOS-9 SST-8T
0 H H εΗ3 H ados- 9 SI-SI s H H εΏ H 3W0S-9 ssi-ει0 HH ε Η3 H ados- 9 SI-SI s HH ε Ώ H 3W0S-9 ssi-ει
0 H H eao H m 9W0 8W0S-9 29ΐ-ετ s H H H 9W0 dz0S-9 ΐ9ΐ-ετ m-zn 0 H H Eao H 9W0 q - 9 09ΐ-ετ s H H H OS-9 6ίΊ-ετ0 HH e ao H m 9W0 8W0S-9 29ΐ-ετ s HHH 9W0 d z 0S-9 ΐ9ΐ-ετ m-zn 0 HH E ao H 9W0 q-9 09ΐ-ετ s HHH OS-9 6ίΊ-ετ
0 H H H OS- 9 8Η- εΐ s H H H m 9WS-9 ΐ-ετ0 H H H OS- 9 8Η- εΐ s H H H m 9WS-9 ΐ-ετ
06-68 0 H H H 3W0 m aWS-9 9Η -06-68 0 H H H 3W0 m aWS-9 9Η-
0 H H £Ώ H 3 HS-9 0 HH £ Ώ H 3 HS-9
\z -oz\ 0 H H εΗ0 H AxoiA3JBdOJ,j-9 -εΐ\ z -oz \ 0 HH ε Η0 H AxoiA3JBdOJ, j-9 -εΐ
2ΐΐ-ΐΐΐ 0 H H H ( xo{Auojins3uanioj,-d)-9 ε ΐ- ει 3 0 H H eao H I-JdQ-9 ζη-2ΐ2ΐΐ-ΐΐΐ 0 HHH (xo {Auojins3uanioj, -d) -9 ε ΐ- ει 3 0 HH e ao H I-JdQ-9 ζη-2ΐ
0 H H 2H0zH00- 3W0-90 HH 2 H0 z H00-3W0-9
0 H H ιΏ H 3W0-9 θ -ετ0 HH ι Ώ H 3W0-9 θ -ετ
0 H H εΗ3 H aWO-9 6ει- ει s H H Eao H 3W0 聊 嚷- 9 8εΐ-ετ n-zQ 0 . H H H 8W0 3W0-9 Α2ΐ-εΐ0 HH ε Η3 H aWO-9 6ει- ει s HH E ao H 3W0 Liaison- 9 8εΐ-ετ n-zQ 0 .HHH 8W0 3W0-9 Α2ΐ-εΐ
8ト S 0 H H H 9K0 HO-9 9ει-ετ8 G S 0 H H H 9K0 HO-9 9ει-ετ
88-丄 8 0 H H sao H 3W0 130-9 88- 丄 8 0 HH s ao H 3W0 130-9
0 H H H 3H0 13003HNS30-9 0 H H H 3H0 13003HNS30-9
0 H H eao H 9W0 o U-X8HHNO0O-9 εετ-ετ n\-m 0 H H H 3 3-ΧΘΗΗΝ030-9 SSI-SI0 HH e ao H 9W0 o U-X8HHNO0O-9 εετ-ετ n \ -m 0 HHH 3 3-ΧΘΗΗΝ030-9 SSI-SI
02Ι-8Π 0 H H sao H a ■030 - 9 ΐθΐ-ετ 02Ι-8Π 0 HH s ao H a 030-9 ΐθΐ-ετ
0 H H H awo 3Wz0SzH30-9 οετ-ετ0 HHH awo 3W z 0S z H30-9 οετ-ετ
0 H H sao H 3 8NSzH30-9 62Ϊ-8Ϊ0 HH s ao H 3 8NS z H30-9 62Ϊ-8Ϊ
0 H H H a H30-9 82ΐ-ετ 爾珊 z "人 εζ入 V 5a 'a 0 HHH a H30-9 82 ΐ-ετ z z "people ε input V 5 a 'a
(#. ^) \ m  (#. ^) \ m
89 IOO/f6dT/X3d 第 14 表 89 IOO / f6dT / X3d Table 14
Figure imgf000071_0001
Figure imgf000071_0001
No. Xn R . R2 R3 2 5 2 6 Y 2 7 A Z 物性値-1 H O e OMe H H OH H CR3 0 No. Xn R. R 2 R 3 2 5 2 6 Y 27 AZ Physical property value -1 HO e OMe HH OH H CR 30
- 2 H OMe OMe H H OH Me CR3 0-2 H OMe OMe HH OH Me CR 30
-3 H OMe OMe . H H OH CF3 CR3 0-3 H OMe OMe .HH OH CF 3 CR 30
-4 H OMe OMe H H OH Ph CR3 0-4 H OMe OMe HH OH Ph CR 30
-5 H OMe OMe H H OH C I CR3 0-5 H OMe OMe HH OH CI CR 30
-6 H OMe OMe H H OH OH CR3 0 -6 H OMe OMe HH OH OH CR 30
- 7 H OMe OMe H H OH OMe C vRlv 3 n u-7 H OMe OMe H H OH OMe C vRlv 3 n u
-8 H OMe OMe H H OH SMe CR3 0-8 H OMe OMe HH OH SMe CR 30
-9 H OMe OMe H H OH S02Me CR3 0-9 H OMe OMe HH OH S0 2 Me CR 30
-10 H OMe OMe H H OH SH CR3 0-10 H OMe OMe HH OH SH CR 30
-11 H OMe OMe H H OH 腦 e CR3 0 -11 H OMe OMe HH OH brain e CR 30
- 12 H OMe OMe H H OH CN CR3 0-12 H OMe OMe HH OH CN CR 30
-13 H OMe OMe H Me H H CR3 0 90-14 H OMe OMe H Me OH Me CR3 0-13 H OMe OMe H Me HH CR 30 90 -14 H OMe OMe H Me OH Me CR 30
-15 H OMe OMe H Me Me OH CR3 0-15 H OMe OMe H Me Me OH CR 30
-16 H OMe OMe H Me C I Me CR3 0-16 H OMe OMe H Me CI Me CR 30
-17 H OMe OMe H Me Me C I CR3 0-17 H OMe OMe H Me Me CI CR 30
-18 H OMe OMe H Me C I C I CR3 0-18 H OMe OMe H Me CICI CR 30
-19 H OMe OMe H Me H Me CR3 0-19 H OMe OMe H Me H Me CR 3 0
-20 H OMe OMe K Me H Me CR3 0-20 H OMe OMe K Me H Me CR 3 0
-21 H OMe OMe H Ph Me C I CR3 0-21 H OMe OMe H Ph Me CI CR 30
-22 H OMe OMe H Ph C I Me CR3 0-22 H OMe OMe H Ph CI Me CR 30
-23 H OMe OMe H Py* H H CR3 0 175-176-23 H OMe OMe H Py * HH CR 3 0 175-176
* P yは 4 , 6 —ジメ トキシピリ ミ ジン _ 2 —ィルを表す c * P y represents 4, 6 —dimethoxypyrimidine _ 2 —yl c
Figure imgf000072_0001
Figure imgf000072_0001
碎歸一  Return
N P / P / 109 N P / P / 109
7 1 7 1
Figure imgf000073_0001
Figure imgf000073_0001
No. n Ri R2 R3 Y31 133 132 A Z 物性値-1 . H OMe OMe H 2-pyridy 1 H CI CR3 0 No. n Ri R 2 R3 Y31 133 132 AZ Physical property values -1. H OMe OMe H 2-pyridy 1 H CI CR 30
- 2 H OMe OMe H 2-pyridy 1 H OH CR3 0-2 H OMe OMe H 2-pyridy 1 H OH CR 30
-3 H OMe OMe H Et H CI CR3 0-3 H OMe OMe H Et H CI CR 30
-4 H OMe OMe H Et H H CR3 0-4 H OMe OMe H Et HH CR 30
-5 6-F OMe OMe H Et H OH CR3 0-5 6-F OMe OMe H Et H OH CR 30
-6 6-C1 OMe OMe H Et H OH CR3 0-6 6-C1 OMe OMe H Et H OH CR 30
-7 H OMe OMe H Me H CI CR3 0-7 H OMe OMe H Me H CI CR 30
-8 H OMe -0CH2CH2 Me H H CR3 0-8 H OMe -0CH 2 CH 2 Me HH CR 30
-9 H OMe OMe H Me H OH CR3 0-9 H OMe OMe H Me H OH CR 30
-10 6- CI OMe -OCH2CH2 Me H OH CR3 0-10 6- CI OMe -OCH2CH2 Me H OH CR 30
-11 6-F OMe -OCH2CH2 Me H OH CR3 0-11 6-F OMe -OCH2CH2 Me H OH CR 30
-12 H OMe OMe H Ph H CI CR3 0-12 H OMe OMe H Ph H CI CR 30
-13 H OMe -0CH2CH2 Ph H H CR3 0-13 H OMe -0CH 2 CH 2 Ph HH CR 30
-14 H OMe OMe H Ph H OH CR3 0 第 17 表 -14 H OMe OMe H Ph H OH CR 30 Table 17
RiRi
Figure imgf000074_0001
Figure imgf000074_0001
No. Xn R. R2 R3 Y34 Y3 a Y36 Y37 A Z 物性値-1 H OMe OMe H H H H H CR3 0No. Xn R. R 2 R 3 Y34 Y3 a Y36 Y37 AZ Property-1 H OMe OMe HHHHH CR 30
-2 H OMe OMe H H H CN H CR3 0 169-170-3 H OMe OMe H H H COOMe H CR3 0-2 H OMe OMe HHH CN H CR 3 0 169-170-3 H OMe OMe HHH COOMe H CR 30
-4 H OMe OMe H H H COOEt H CR3 0 153-155-5 H OMe OMe H H H COOH H CR3 0 220-225-6 H OMe OMe H H H NO 2 H CR3 0-4 H OMe OMe HHH COOEt H CR 3 0 153-155-5 H OMe OMe HHH COOH H CR 3 0 220-225-6 H OMe OMe HHH NO 2 H CR 30
-7 H OMe -0CH2 CH2- H H CN H CRa 0-7 H OMe -0CH 2 CH 2 -HH CN H CR a 0
-8 H OMe -OCH2 CH2- H H COOMe H CR3 0-8 H OMe -OCH2 CH 2 -HH COOMe H CR 30
-9 H OMe OMe H CHO H CN H CR3 0-9 H OMe OMe H CHO H CN H CR 30
-10 H OMe OMe H CHO H COOEt H CR3 0-10 H OMe OMe H CHO H COOEt H CR 30
-11 6- CI OMe OMe H H H CN H CR3 0-11 6- CI OMe OMe HHH CN H CR 30
-12 6-F OMe OMe H H H CN H CR3 0-12 6-F OMe OMe HHH CN H CR 30
-13 6-C1 OMe OMe H H H CN H CR3 s-13 6-C1 OMe OMe HHH CN H CR 3 s
-14 6-F OMe OMe H H H CN H CR3 s-14 6-F OMe OMe HHH CN H CR 3 s
-15 6-F OMe OMe H H H COOMe H CR3 0 180-181-16 6- CI OMe OMe H H H COOMe H CR3 0-15 6-F OMe OMe HHH COOMe H CR 3 0 180-181-16 6- CI OMe OMe HHH COOMe H CR 30
-17 6-OPy* OMe OMe H H H COOEt H CR3 0 165-168-17 6-OPy * OMe OMe HHH COOEt H CR 3 0 165-168
* P yは 4 , 6—ジメ トキシピリ ミ ジン— 2—ィルを表す c 第 18 表 * P y represents 4, 6-dimethoxypyrimidine-2-yl c Table 18
Figure imgf000075_0001
Figure imgf000075_0001
No. Xn R, R2 R3 Y38 A Z 物性値-1 H OMe OMe H H CR3 0 146-148-2 H OMe OMe H Me CR3 0No. Xn R, R 2 R 3 Y38 AZ Physical property value -1 H OMe OMe HH CR 3 0 146-148-2 H OMe OMe H Me CR 30
-3 ' H OMe OMe H Et CR3 0 amorphous-4 H OMe OMe H i-Pr CR3 0 100「102-5 H OMe OMe H Ph CR3 0-3 'H OMe OMe H Et CR 30 amorphous-4 H OMe OMe Hi-Pr CR 30 100 `` 102-5 H OMe OMe H Ph CR 30
-6 H OMe OMe H CH2Ph CR3 0 Gum-7 H OMe OMe H CH20H CR3 0 -6 H OMe OMe H CH 2 Ph CR 30 Gum-7 H OMe OMe H CH 20 H CR 30
- 8 H OMe OMe H Na CR3 0 123-127-9 H OMe OMe H CH2SMe CR3 0 Gum-10 H OMe OMe H CH2S02Me CR3 0 54-56 - 11 H OMe OMe H CH2OMe CR3 0 86-89-12 H OMe OMe H CH2COOMe CR3 0 amorphous-13 H OMe OMe H CH2COOH CR3 0 170-172-14 H OMe OMe H CH2CN CR3 0 - 8 H OMe OMe H Na CR 3 0 123-127-9 H OMe OMe H CH 2 SMe CR 3 0 Gum-10 H OMe OMe H CH 2 S0 2 Me CR 3 0 54-56 - 11 H OMe OMe H CH 2 OMe CR 3 0 86-89-12 H OMe OMe H CH 2 COOMe CR 3 0 amorphous-13 H OMe OMe H CH2COOH CR 3 0 170-172-14 H OMe OMe H CH 2 CN CR 30
- 15 H OMe OMe H Ac CR3 0-15 H OMe OMe H Ac CR 30
-16 H OMe OMe H 2-Cl-PhCO CR3 0-16 H OMe OMe H 2-Cl-PhCO CR 30
-17 H OMe OMe H S02Me CR3 0 91-93-18 H OMe OMe H SO2T0I-P CR3 0 -17 H OMe OMe H S0 2 Me CR 3 0 91-93-18 H OMe OMe H SO2T0I-P CR 3 0
-19 H OMe OMe H S02NMe2 CR3 0-19 H OMe OMe H S0 2 NMe 2 CR 3 0
-20 H OMe OMe H NH2 CR3 0-20 H OMe OMe H NH 2 CR 3 0
-21 H OMe OMe H NHCOOEt CR3 0 -21 H OMe OMe H NHCOOEt CR 30
- 22 H OMe OMe H NHPh CR3 0-22 H OMe OMe H NHPh CR 30
-23 6 - CI OMe OMe H H CR3 0-23 6-CI OMe OMe HH CR 30
-24 6 - CI OMe OMe H Me CR3 0 -24 6-CI OMe OMe H Me CR 30
- 25 6-C1 OMe OMe H c-Hex CR3 0-25 6-C1 OMe OMe H c-Hex CR 30
-26 H OMe OMe H K CR3 0 230-235-27 6- CI OMe OMe H Me CR3 s-26 H OMe OMe HK CR 3 0 230-235-27 6- CI OMe OMe H Me CR 3 s
-28 6 - CI OMe OMe H c-Hex CR3 s-28 6-CI OMe OMe H c-Hex CR 3 s
-29 H OMe OMe H H CR3 s-29 H OMe OMe HH CR 3 s
-30 6-F OMe OMe H H C 3 0-30 6-F OMe OMe HHC 30
-31 6-F OMe OMe H H CR3 s-31 6-F OMe OMe HH CR 3 s
-32 H OMe OMe H t-Bu CR3 0-32 H OMe OMe H t-Bu CR 30
-33 H OMe OMe H 2-Pyridyl CR3 0 OM u ι-33 H OMe OMe H 2-Pyridyl CR 30 OM u ι
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Figure imgf000077_0001
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No. X' n R, R2 Rs A Y23 Y24 Z 物性値-1 H Me Me H CR3 H H 0 No. X 'n R, R 2 Rs A Y23 Y24 Z Physical property values -1 H Me Me H CR 3 HH 0
- 2 3， 5-Dimethyl OMe OMe H CR3 H H 0 Gum-3 3-Bu-t OMe OMe H CR3 H H 0 1.548-4 4- C】 OMe OMe H CR3 H H 0 92 - 95-5 2-OMe OMe OMe H CR3 H H 0-23, 5-Dimethyl OMe OMe H CR 3 HH 0 Gum-3 3-Bu-t OMe OMe H CR 3 HH 0 1.548-4 4- C] OMe OMe H CR 3 HH 0 92-95-5 2- OMe OMe OMe H CR 3 HH 0
-6 H OMe OMe H CR3 H Bn 0-6 H OMe OMe H CR 3 H Bn 0
-7 4-OMe OMe OMe H CR3 H H 0 94-96-8 4-CN OMe OMe H CR3 H H 0 Gum - 9 2， 5-Dimethyl OMe OMe H CR3 H H 0 Gum-10 3， 5 - Dimethoxy OMe OMe H CR3 H H 0 107-110-11 H OMe OMe H CR3 Me H o-7 4-OMe OMe OMe H CR 3 HH 0 94-96-8 4-CN OMe OMe H CR 3 HH 0 Gum-92,5-Dimethyl OMe OMe H CR 3 HH 0 Gum-10 3,5-Dimethoxy OMe OMe H CR 3 HH 0 107-110-11 H OMe OMe H CR 3 Me Ho
-12 3-F OMe OMe H CR3 H H 0-12 3-F OMe OMe H CR 3 HH 0
-13 2, 4, 6-Trimethyl OMe OMe H CR3 H H 0 163-165-14 2-Ph OMe OMe H CR3 H H 0 119-121-15 4-N02 OMe OMe H CR3 H H 0-13 2, 4, 6-Trimethyl OMe OMe H CR 3 HH 0 163-165-14 2-Ph OMe OMe H CR 3 HH 0 119-121-15 4-N0 2 OMe OMe H CR 3 HH 0
-16 3, 4- Dimethyl OMe OMe H CR3 H H 0 Gum-17 H OMe OMe H CR3 H Me 0 1.571-18 2-NO2 OMe OMe H CR3 H H 0-16 3, 4-Dimethyl OMe OMe H CR 3 HH 0 Gum-17 H OMe OMe H CR 3 H Me 0 1.571-18 2-NO2 OMe OMe H CR 3 HH 0
-19 2-NH2-4-CF3 OMe OMe H CR3 H H 0-19 2-NH2-4-CF3 OMe OMe H CR 3 HH 0
-20 2， 6-Dimethyl OMe OMe H CR3 H H 0 141-143-21 2-(CH)4-3 OMe OMe H CR3 H H 0 89-92-22 H OMe OMe H CR3 H H 0 1.603-23 2-F OMe OMe H CR3 H H 0-20 2,6-Dimethyl OMe OMe H CR 3 HH 0 141-143-21 2- (CH) 4 -3 OMe OMe H CR 3 HH 0 89-92-22 H OMe OMe HCR 3 HH 0 1.603-23 2-F OMe OMe H CR 3 HH 0
-24 2-CONH2 OMe OMe H CR3 H H 0-24 2-CONH2 OMe OMe H CR 3 HH 0
-25 3-NO2 OMe OMe H CR3 H H 0 /175 -25 3-NO2 OMe OMe H CR 3 HH 0 / 175
7 6 7 6
20 表 （つづき） 20 Table (continued)
No. χ' η R, R2 R3 A Y 23 Y 24 Z 物性値-26 3-CN OMe OMe H CR3 H H 0No. χ ' η R, R 2 R 3 AY 23 Y 24 Z Physical properties -26 3-CN OMe OMe H CR 3 HH 0
-27 4 - Me OMe OMe H CR3 H H 0 125-127-28 4-F OMe OMe H CR3 H H 0 73-75-29 H OMe OMe N H H 0 97-99-30 3-NMe2 OMe OMe H CR3 H H 0 1.594-31 3-Me OMe OMe H CR3 H H 0 70-72-32 3 - CI OMe OMe H CR3 H H 0-27 4-Me OMe OMe H CR 3 HH 0 125-127-28 4-F OMe OMe H CR 3 HH 0 73-75-29 H OMe OMe NHH 0 97-99-30 3-NMe 2 OMe OMe H CR 3 HH 0 1.594-31 3-Me OMe OMe H CR 3 HH 0 70-72-32 3-CI OMe OMe H CR 3 HH 0
-33 2- Me OMe OMe H CR3 H H 0 130-132-34 2, 3 - Dimethyl OMe OMe H CR3 H H 0 80-82-35 3-OMe OMe OMe H CR3 H H 0 Gum-36 2-NO2-CF3 OMe OMe H CR3 H H 0 108-109-37 2-C1 OMe OMe H CR3 H H 0-33 2-Me OMe OMe H CR 3 HH 0 130-132-34 2, 3-Dimethyl OMe OMe H CR 3 HH 0 80-82-35 3-OMe OMe OMe H CR 3 HH 0 Gum-36 2-NO2 -CF3 OMe OMe H CR 3 HH 0 108-109-37 2-C1 OMe OMe H CR 3 HH 0
-38 2, 4- Dimethyl OMe OMe H CR3 H H 0 99-102-39 2-CN OMe OMe H CR3 H H 0-38 2, 4-Dimethyl OMe OMe H CR 3 HH 0 99-102-39 2-CN OMe OMe H CR 3 HH 0
-40 H OMe OMe H CR3 Me Me 0 -40 H OMe OMe H CR 3 Me Me 0
第 21 表 Table 21
Figure imgf000079_0001
Figure imgf000079_0001
No. Xn Ri R2 R3 Y 0 Y41 A Z 物性値-1 H OMe OMe H H H CR3 0No. Xn Ri R 2 R 3 Y 0 Y41 AZ Physical property value -1 H OMe OMe HHH CR 30
-2 6-F O e OMe H H H CR3 0 -2 6-FO e OMe HHH CR 30
- 3 6- CI OMe OMe H H H CR3 0-3 6- CI OMe OMe HHH CR 30
-4 H OMe OMe H H H CR3 S-4 H OMe OMe HHH CR 3 S
-5 H OMe OMe H Me H CR3 0 109-110-6 6 - CI OMe OMe H Me H CR3 0-5 H OMe OMe H Me H CR 3 0 109-110-6 6-CI OMe OMe H Me H CR 30
-7 6-F OMe OMe H Me H CR3 0-7 6-F OMe OMe H Me H CR 30
-8 6-OMe OMe OMe H Me H CR3 0-8 6-OMe OMe OMe H Me H CR 30
-9 H OMe OMe H 4-Cl-Ph H CR3 0-9 H OMe OMe H 4-Cl-Ph H CR 30
-10 H OMe OMe H Ph H CR3 0-10 H OMe OMe H Ph H CR 30
-11 H OMe OMe H Me Me CR3 0-11 H OMe OMe H Me Me CR 30
-12 6-F OMe OMe H Me Me CR3 0-12 6-F OMe OMe H Me Me CR 30
-13 6 - CI OMe OMe H Me Me CR3 0-13 6-CI OMe OMe H Me Me CR 3 0
-14 6 - Br OMe OMe H Me Me CR3 0-14 6-Br OMe OMe H Me Me CR 30
-15 6-1 OMe OMe H Me Me CR3 0-15 6-1 OMe OMe H Me Me CR 3 0
-16 H OMe OMe H NHPh Me CR3 0 -16 H OMe OMe H NHPh Me CR 30
Figure imgf000080_0001
Figure imgf000080_0001
No. Xn Ri R2 R3 Y4 2 I 43 A z 物性値-1 H OMe OMe H H H CR3 0No. Xn Ri R2 R3 Y4 2 I 43 Az Physical property -1 H OMe OMe HHH CR 30
-2 6-F OMe OMe H H H CR3 0-2 6-F OMe OMe HHH CR 30
-3 6 - CI OMe OMe H H H CR3 0-3 6-CI OMe OMe HHH CR 30
-4 H OMe OMe H /ハ ヽ -4 H OMe OMe H / C ヽ
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-5 H OMe OMe H H H CR3 s-5 H OMe OMe HHH CR 3 s
-6 H OMe OMe H H Me CR3 0-6 H OMe OMe HH Me CR 30
-7 H OMe OMe H H Ph CR3 0-7 H OMe OMe HH Ph CR 30
-8 H OMe OMe H H OH CR3 0-8 H OMe OMe HH OH CR 30
-9 H OMe OMe H H CI CR3 0-9 H OMe OMe HH CI CR 30
-10 H OMe OMe H H SMe CR3 0-10 H OMe OMe HH SMe CR 30
-11 H OMe OMe H H 匪 e CR3 0-11 H OMe OMe HH Marauder e CR 3 0
-12 H OMe OMe H H COOMe CR3 0-12 H OMe OMe HH COOMe CR 30
-13 H OMe OMe H H COOH CR3 0-13 H OMe OMe HH COOH CR 30
-14 H OMe OMe H H OMe CR3 0-14 H OMe OMe HH OMe CR 30
-15 6 - CI OMe OMe H H COOMe CR3 0-15 6-CI OMe OMe HH COOMe CR 30
-16 6-F OMe OMe H H CF3 CR3 0-16 6-F OMe OMe HH CF 3 CR 30
-17 6 - CI OMe OMe H H CF3 CR3 0
Figure imgf000081_0001
-17 6-CI OMe OMe HH CF 3 CR 3 0
Figure imgf000081_0001
第 24 表 Table 24
Figure imgf000082_0001
Figure imgf000082_0001
No. Xn Ri R2 R3 A Y38 Z 物性値-1 H OMe OMe H CR3 Me 0 No. Xn Ri R 2 R 3 A Y38 Z Physical properties -1 H OMe OMe H CR 3 Me 0
- 2 H OMe OMe H CR3 Ac 0 -2 H OMe OMe H CR 3 Ac 0
- 3 H OMe OMe H CR3 S02Me 0-3 H OMe OMe H CR 3 S0 2 Me 0
-4 H OMe -0CH2CH2 CR3 Me 0-4 H OMe -0CH 2 CH 2 CR 3 Me 0
-5 H OMe -0CH2CH2 CR3 Ac 0-5 H OMe -0CH 2 CH 2 CR 3 Ac 0
-6 H OMe -OCH2CH2 CR3 S02Me 0 -6 H OMe -OCH2CH2 CR 3 S0 2 Me 0
第 25 表 Table 25
2 Two
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Figure imgf000083_0001
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Figure imgf000083_0001
No. Xn R. R2 R3 A Y23 Y24 Z 物性値-1 . H OMe OMe H CR3 H H 0 135-138-2 H O e OMe H CR3 H COOEt 0No. Xn R. R 2 R 3 A Y23 Y24 Z Physical properties -1. H OMe OMe H CR 3 HH 0 135-138-2 HO e OMe H CR 3 H COOEt 0
-3 H OMe OMe H CR3 H COOMe 0-3 H OMe OMe H CR 3 H COOMe 0
-4 H OMe OMe H CR3 H COOH 0-4 H OMe OMe H CR 3 H COOH 0
-5 H OMe - 0CH2CH2 CR3 H H 0-5 H OMe-0CH 2 CH 2 CR 3 HH 0
-6 H OMe -0CH2CH2 CR3 H COOEt 0-6 H OMe -0CH 2 CH 2 CR 3 H COOEt 0
-7 H OMe -OCH2CH2 CR3 H COOMe 0-7 H OMe -OCH2CH2 CR 3 H COOMe 0
-8 H OMe -0CH2CH2 CR3 H COOH 0-8 H OMe -0CH 2 CH 2 CR 3 H COOH 0
-9 H Me Me H CR3 H H 0-9 H Me Me H CR 3 HH 0
-10 H OMe CI H CR3 H H 0-10 H OMe CI H CR 3 HH 0
-11 H OMe OMe H CR3 H p-Toluenesulfony 1 0 Gum -11 H OMe OMe H CR 3 H p-Toluenesulfony 10 Gum
109 109
8 2 8 2
Figure imgf000084_0001
Figure imgf000084_0001
No. Xn R, R2 R3 Q-Yn A B Z 物性値-1 H OMe OMe H 3-methoxy car bony 1 pyr rol-4-yl CRS N 0No. Xn R, R 2 R 3 Q-Yn ABZ Physical properties -1 H OMe OMe H 3-methoxy car bony 1 pyr rol-4-yl CR S N 0
-2 H OMe OMe H 3-cyanopyrrol-4-yl CR3 N 0-2 H OMe OMe H 3-cyanopyrrol-4-yl CR 3 N 0
-3 H OMe OMe H pyrazol-4-yl CR3 N 0-3 H OMe OMe H pyrazol-4-yl CR 3 N 0
-4 H OMe OMe H isoxazol-4-yl CR3 N 0-4 H OMe OMe H isoxazol-4-yl CR 3 N 0
-5 H OMe OMe H thiazol-2-yl CR3 N 0-5 H OMe OMe H thiazol-2-yl CR 3 N 0
-6 H . OMe OMe H imidazol-4-yl CR3 N 0-6 H. OMe OMe H imidazol-4-yl CR 3 N 0
-7 H OMe OMe oxazol-4-yl N N 0-7 H OMe OMe oxazol-4-yl N N 0
-8 H OMe OMe tetrazol-5-yl N N 0-8 H OMe OMe tetrazol-5-yl N N 0
-9 H OMe OMe 3-cyanopyrrol-4-yl N N 0-9 H OMe OMe 3-cyanopyrrol-4-yl N N 0
-10 H OMe OMe pyrazol-4-yl N N 0 -10 H OMe OMe pyrazol-4-yl N N 0
- 11 H OMe OMe isoxazol-4-yl N N 0-11 H OMe OMe isoxazol-4-yl N N 0
-12 H OMe OMe thiazol-2-yl N N 0-12 H OMe OMe thiazol-2-yl N N 0
-13 H OMe OMe imidazol-4-yl N N 0-13 H OMe OMe imidazol-4-yl N N 0
-14 H OMe OMe H 3-methyl-l, 2, 4 - oxadiazo卜 5 - yl CR3 N 0 128-132-15 H OMe OMe H 5-trif luoromethyl-l, 2, 4 - oxadiazoト 3-yl CR3 N 0-14 H OMe OMe H 3-methyl-l, 2, 4-oxadiazo 5-yl CR 3 N 0 128-132-15 H OMe OMe H 5-trif luoromethyl-l, 2, 4-oxadiazo 3 -yl CR 3 N 0
-16 H OMe OMe H 4-(p-toluenesulf onyl)-2-oxazol in-5-y 1 CR3 N 0 Gum-17 H OMe OMe H 5-trif luoromethyl-l, 3, 4 - triazo卜 2 - yl CR3 N 0-16 H OMe OMe H 4- (p-toluenesulf onyl) -2-oxazol in-5-y 1 CR 3 N 0 Gum-17 H OMe OMe H 5-trif luoromethyl-l, 3, 4-triazo 2- yl CR 3 N 0
-18 H OMe OMe H 3-e thoxy car bony lpyrrol-4-yl CR3 N 0 75-80-19 H OMe OMe H 5-trif luoromethyl-l, 3, 4 - triazo卜 3 - yl CR3 C 0-18 H OMe OMe H 3-e thoxy car bony lpyrrol-4-yl CR 3 N 0 75-80-19 H OMe OMe H 5-trif luoromethyl-l, 3, 4-triazo 3-yl CR 3 C 0
-20 6-F OMe OMe H 5-trif luoromethyl-l, 3, 4 - triazo卜 3 - yl CR3 C 0-20 6-F OMe OMe H 5-trif luoromethyl-l, 3, 4-triazo tri 3-yl CR 3 C 0
-21 H OMe OMe H 6-pyridazinon-3-yl CRS C 0-21 H OMe OMe H 6-pyridazinon-3-yl CR S C 0
-22 H OMe OMe H l-methylpyridazin-6-on-3-y 1 CR3 C 0-22 H OMe OMe H l-methylpyridazin-6-on-3-y 1 CR 3 C 0
-23 H OMe OMe H 4, 5-di me thoxy car bony 1 pyr rol-2-yl CR3 C 0-23 H OMe OMe H 4, 5-di me thoxy car bony 1 pyr rol-2-yl CR 3 C 0
-24 H OMe OMe H pyridazin-6-on-3-yl CR3 C 0 154-156-25 H OMe OMe H l-(4, 6-dimethoxypyriraidin-2-yl )- CR3 C 0 175-177 -24 H OMe OMe H pyridazin-6-on-3-yl CR 3 C 0 154-156-25 H OMe OMe H l- (4, 6-dimethoxypyriraidin-2-yl)-CR 3 C 0 175-177
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Figure imgf000087_0001
Figure imgf000087_0001
No. Xn Ri R2 Rs I 54 A I 物性値No. Xn Ri R 2 Rs I 54 AI Physical properties
29 - 1 H OMe OMe H H CR3 0 170-17229-1 H OMe OMe HH CR 30 170-172
29-2 H OMe -0CH2CH2- H CR3 0 29-2 H OMe -0CH 2 CH 2 -H CR 30
29-3 H OMe OMe H H CR3 s 29-3 H OMe OMe HH CR 3 s
29-4 H OMe -0CH2CH2- H CR3 s29-4 H OMe -0CH 2 CH 2 -H CR 3 s
9-5 H UMe Me H H CR3 0 9-5 H UMe Me HH CR 30
29-6 H OMe CF3 H H CR3 0 29-6 H OMe CF 3 HH CR 30
29-7 H OMe Me 2 H H CR3 0 29-7 H OMe Me 2 HH CR 3 0
29-8 H OMe -OCH=CH- H CR3 0 29-8 H OMe -OCH = CH- H CR 30
29 - 9 H OMe OMe H Me CR3 0 29-9 H OMe OMe H Me CR 30
29-10 H OMe -0CH2CH2- Me CR3 0 29-10 H OMe -0CH 2 CH 2 -Me CR 3 0
29-11 H OMe OMe H Me CR3 s 29-11 H OMe OMe H Me CR 3 s
29-12 H OMe -OCH2CH2- Me CR3 s 29-12 H OMe -OCH2CH2- Me CR 3 s
29-13 H OMe OMe CI Me CR3 0 29-13 H OMe OMe CI Me CR 3 0
29-14 H OMe OMe Br Me CR3 0 29-14 H OMe OMe Br Me CR 30
29-15 H Me Me H Me CR3 0 29-15 H Me Me H Me CR 3 0
29-16 6 - CI OMe OMe H H CR3 0 29-16 6-CI OMe OMe HH CR 30
Figure imgf000088_0001
Figure imgf000088_0001
No. Xn R, R2 R3 Y 55 A Z 物性値
Figure imgf000088_0002
No. Xn R, R 2 R 3 Y 55 AZ Physical properties
Figure imgf000088_0002
-2 H OMe OMe H H CR3 0-2 H OMe OMe HH CR 30
-3 H OMe -OCH2CH2- Me CR3 0-3 H OMe -OCH2CH2-Me CR 30
-4 H Me Me H Me CR3 0-4 H Me Me H Me CR 30
-5 H OMe OMe H Me CR3 0-5 H OMe OMe H Me CR 30
-6 H OMe OMe CI Me CR3 0-6 H OMe OMe CI Me CR 30
-7 H OMe OMe Br Me CR3 0-7 H OMe OMe Br Me CR 30
-8 H OMe -OCH2CH2- Me CR3 s-8 H OMe -OCH2CH2- Me CR 3 s
-9 H OMe OMe H Me CR3 S-9 H OMe OMe H Me CR 3 S
-10 6 - CI OMe OMe H NH2 CR3 0-10 6-CI OMe OMe H NH 2 CR 3 0
-11 6-C1 OMe OMe H NH2 CR3 s-11 6-C1 OMe OMe H NH 2 CR 3 s
-12 6-C1 OMe OMe H OEt CR3 0-12 6-C1 OMe OMe H OEt CR 30
-13 6- CI OMe OMe H OEt CR3 s-13 6- CI OMe OMe H OEt CR 3 s
-14 6-C1 OMe OMe H Ph CR3 0-14 6-C1 OMe OMe H Ph CR 30
-15 6- CI OMe OMe H Ph CR3 s-15 6- CI OMe OMe H Ph CR 3 s
-16 H OMe -0CH=CH- H SMe CR3 0-16 H OMe -0CH = CH- H SMe CR 30
-17 H OMe CF3 H SMe CR3 0-17 H OMe CF 3 H SMe CR 30
-18 H OMe Me H SMe CR3 0-18 H OMe Me H SMe CR 30
-19 H OMe NMe2 H SMe CR3 0-19 H OMe NMe 2 H SMe CR 3 0
-20 H OMe - 0CH2CH2 - SMe CR3 s-20 H OMe-0CH 2 CH 2 -SMe CR 3 s
-21 H OMe OMe H SMe CR3 s-21 H OMe OMe H SMe CR 3 s
-22 6 - CI OMe OMe H S02Me CR3 0-22 6-CI OMe OMe H S0 2 Me CR 30
-23 6- CI OMe OMe H S02Me C 3 s ！ -23 6- CI OMe OMe H S0 2 Me C 3 s !
oo 第 31 表  oo table 31
化合物 Compound
化合物の NMRデータ （<5値）  Compound NMR data (<5 values)
番 号 No.
5-12 3.80(s, 6H), 5.78(s, 1H)， 6.70(d, 1H),7.25-7.52 (m, 3H), 8.05(dd, 1H)， 8.23(d, IH)  5-12 3.80 (s, 6H), 5.78 (s, 1H), 6.70 (d, 1H), 7.25-7.52 (m, 3H), 8.05 (dd, 1H), 8.23 (d, IH)
6-3 3.78(s, 6H), 5.71 (s, IH), 6.77(d, 1H)， 7.25-7.52 (m, 3H), 7.98-8.03  6-3 3.78 (s, 6H), 5.71 (s, IH), 6.77 (d, 1H), 7.25-7.52 (m, 3H), 7.98-8.03
(m, 1H),8.37(d, IH)  (m, 1H), 8.37 (d, IH)
10-5 3.82(s, 6H),5.74(s, 1H),7.18(t, 2H)， 7.27(s, 1H)， 7.35(s， 1H)， 7.50  10-5 3.82 (s, 6H), 5.74 (s, 1H), 7.18 (t, 2H), 7.27 (s, 1H), 7.35 (s, 1H), 7.50
(t, IH), 7.57(s, IH), 7.96 (m， IH), 8.19 (m, IH)  (t, IH), 7.57 (s, IH), 7.96 (m, IH), 8.19 (m, IH)
10-10 2.23(s, 3H), 3.79(s, 12H), 5.72(s, 2H)， 7.18(d, 2H), 7.24(s, IH), 7.40  10-10 2.23 (s, 3H), 3.79 (s, 12H), 5.72 (s, 2H), 7.18 (d, 2H), 7.24 (s, IH), 7.40
10-12 3.80(s， 6H), 3.98(s, 6H), 5.75(s, 1H),7.25(dl, H),7.20(d, IH), 7.39 10-12 3.80 (s, 6H), 3.98 (s, 6H), 5.75 (s, 1H), 7.25 (dl, H), 7.20 (d, IH), 7.39
(s IH) 7 45(t, IH).7 76(s, IH)  (s IH) 7 45 (t, IH). 7 76 (s, IH)
10-14 2.35(s， 6H), 3.80(s, 6H)， 5.72(s, IH), 6.72(s, 1H),7.12-7.20 (m, 2H)，  10-14 2.35 (s, 6H), 3.80 (s, 6H), 5.72 (s, IH), 6.72 (s, 1H), 7.12-7.20 (m, 2H),
7.31 (s, IH), 7.45(t, IH), 7.68(s, IH)  7.31 (s, IH), 7.45 (t, IH), 7.68 (s, IH)
1.40(s,9H),3.81(s, 6H),5.76(s, IH), 7.19-7.28 (m, IH), 7.36-7.46 (m, IH), 7.49(s, IH), 7.83(d, IH), 7.90(s, IH)  1.40 (s, 9H), 3.81 (s, 6H), 5.76 (s, IH), 7.19-7.28 (m, IH), 7.36-7.46 (m, IH), 7.49 (s, IH), 7.83 (d, IH), 7.90 (s, IH)
13-70 2.35(s, 6H), 6.72(s, IH), 7.21-7.37 (m, 2H), 7.40(s, IH), 7.35-7.45  13-70 2.35 (s, 6H), 6.72 (s, IH), 7.21-7.37 (m, 2H), 7.40 (s, IH), 7.35-7.45
(m, 1H),7.87(s, IH)  (m, 1H), 7.87 (s, IH)
2 19(s 3H) 3 76(s, 6H) 5 70(s, IH) 7 20(dd IH) 7 40(s IH) 7 42 (d, 1H),7.80(d, IH) 2 19 ( s 3H) 3 76 (s, 6H) 5 70 (s, IH) 7 20 (dd IH) 7 40 (s IH) 7 42 (d, 1H), 7.80 (d, IH)
13-134 1.35(s， 3H), 3.79(s, 6H),4.30 (q, 2H), 5.74(s, 1H),7.20(dt， 2H),7.39  13-134 1.35 (s, 3H), 3.79 (s, 6H), 4.30 (q, 2H), 5.74 (s, 1H), 7.20 (dt, 2H), 7.39
- 7.51 (m, 2H), 7.87(s, IH)  -7.51 (m, 2H), 7.87 (s, IH)
13-142 1.35(d, 6H), 3.78(s, 6H),4.55-4.75 (m, 1H)， 5.70(s， 1H),6.85(t, 2H),  13-142 1.35 (d, 6H), 3.78 (s, 6H), 4.55-4.75 (m, 1H), 5.70 (s, 1H), 6.85 (t, 2H),
7.30(t, IH), 7.43(s, IH), 7.79(s, IH)  7.30 (t, IH), 7.43 (s, IH), 7.79 (s, IH)
18-3 1.52(t, 3H)， 3.74(d, 6H),4.41(dd, 2H),7.28-7.69 (m, 4H)  18-3 1.52 (t, 3H), 3.74 (d, 6H), 4.41 (dd, 2H), 7.28-7.69 (m, 4H)
18-6 3.77(s, 6H)， 5.62(s, 2H)， 5.71(s, 1H),7.02-7.43 (m， 8H),7.55-7.65  18-6 3.77 (s, 6H), 5.62 (s, 2H), 5.71 (s, 1H), 7.02-7.43 (m, 8H), 7.55-7.65
(m, IH)  (m, IH)
18-9 2.16(s， 3H), 3.77(s, 6H)， 5· 49(s, 2H),5.71 (s, 1H),7.33-7.72 (m, 4H) 18-9 2.16 (s, 3H), 3.77 (s, 6H), 5.49 (s, 2H), 5.71 (s, 1H), 7.33-7.72 (m, 4H)
18-12 3.69(s， 3H), 3.77(s, 6H), 5.32(s, 2H),5.71 (s， 1H),7.31-7.73 (m, 4H)18-12 3.69 (s, 3H), 3.77 (s, 6H), 5.32 (s, 2H), 5.71 (s, 1H), 7.31-7.73 (m, 4H)
19-3 1.50(t， 3H)， 3.74(s, 6H),4.57(dd, 2H)， 5.69(s, 1H),7.29-7.56 (m, 3H), 19-3 1.50 (t, 3H), 3.74 (s, 6H), 4.57 (dd, 2H), 5.69 (s, 1H), 7.29-7.56 (m, 3H),
8.22(dd, IH) 第 31 表 （つづき）8.22 (dd, IH) Table 31 (continued)
O  O
化合物 レ Α4ίπ/ NT T 1 T? 一々 ヽ Compound Α4Απ / NT T 1 T?
番 号 No.
19-4 1.53(d, 6Η), 3.73(s, 6H),4.92-5.04 (m, 1H 5.68(s, 1H),7.28-7.55  19-4 1.53 (d, 6Η), 3.73 (s, 6H), 4.92-5.04 (m, 1H 5.68 (s, 1H), 7.28-7.55
(m, 3H), 8.23(dd, IH)  (m, 3H), 8.23 (dd, IH)
19-6 3.68(s 6H),5.60(s IH), 5.67(s, 2H),7.15-7.56 (m, 8H), 8.24(dd, IH) 19-6 3.68 (s 6H), 5.60 (s IH), 5.67 (s, 2H), 7.15-7.56 (m, 8H), 8.24 (dd, IH)
19-9 2.13(s 3H), 3.74(s, 6H), 5.50(s, 2H 5.69(s, IH), 7.31-7.59 (m, 3H), 19-9 2.13 (s 3H), 3.74 (s, 6H), 5.50 (s, 2H 5.69 (s, IH), 7.31-7.59 (m, 3H),
8.24(dd, IH)  8.24 (dd, IH)
19-11 3 32(s, 3H), 3 74(s, 6H), 5 69(s, IH), 5 77(s, 2H), 7.31-7 60 (m, 3H),  19-11 3 32 (s, 3H), 3 74 (s, 6H), 5 69 (s, IH), 5 77 (s, 2H), 7.31-7 60 (m, 3H),
8.25(dd, IH)  8.25 (dd, IH)
1Q c/- ]9 3 74 (s 9H) 5 34(s 2H) 5 68(s IH) 7 31-7 56 (m 3H), 8 23(dd IH) 1Q c /-] 9 3 74 (s 9H) 5 34 (s 2H) 5 68 (s IH) 7 31-7 56 (m 3H), 8 23 (dd IH)
20-2 2.29(s 6H), 3.81 (s 6H),5.72(s, IH), 6.62(d, 2H),6.76(d, 1H 6.89 20-2 2.29 (s 6H), 3.81 (s 6H), 5.72 (s, IH), 6.62 (d, 2H), 6.76 (d, 1H 6.89
(m IH) 7 0 (m IH) 7 32 (t IH) 740(s IH) 7 79(s IH) (m IH) 7 0 (m IH) 7 32 (t IH) 740 (s IH) 7 79 (s IH)
20-8 3.81(s, 6H),5.76(s, 1H 6.95-7.05 (m, 3H),7.17-7.31 (m, 2H 7.40- 7.50 (m, IH), 7.55-7.62 (m, 2H), 7.75(d, IH) 20-8 3.81 (s, 6H), 5.76 (s, 1H 6.95-7.05 (m, 3H), 7.17-7.31 (m, 2H 7.40-7.50 (m, IH), 7.55-7.62 (m, 2H), 7.75 (d, IH)
20-9 2.18(s, 3H), 2.29(s, 3H),3.81 (s 6H 5.73(s, 1H 6.61-6.72 (m, 2H),  20-9 2.18 (s, 3H), 2.29 (s, 3H), 3.81 (s 6H 5.73 (s, 1H 6.61-6.72 (m, 2H),
6.88-7.00 (m, 2H), 7.13(d, IH), 7.26(d, IH), 7.43(s, IH), 7.81(s, IH) 6.88-7.00 (m, 2H), 7.13 (d, IH), 7.26 (d, IH), 7.43 (s, IH), 7.81 (s, IH)
20 - 16 2.22(s, 6H), 3.80(s, 6H 5.72(s, IH), 6.69-6.88 (m, 3H 6.99-7.10 20-16 2.22 (s, 6H), 3.80 (s, 6H 5.72 (s, IH), 6.69-6.88 (m, 3H 6.99-7.10
(m, 2H 7.29(t 1H),7.40(s, 1H),7.79(s, IH)  (m, 2H 7.29 (t 1H), 7.40 (s, 1H), 7.79 (s, IH)
3.78(s, 3H), 3.81(s, 6H), 5.73(s, 1H 6.53-6.69 (m, 3H), 6.92(d, IH), 7.06(d, 1H),7.17-7.40 (m, 3H),7.79(s, IH)  3.78 (s, 3H), 3.81 (s, 6H), 5.73 (s, 1H 6.53-6.69 (m, 3H), 6.92 (d, IH), 7.06 (d, 1H), 7.17-7.40 (m, 3H) , 7.79 (s, IH)
22-4 3.82(s, 6H), 5.78(s, 1H),7.25-7.60 (m, 5H),7.88(d IH), 8.05(d, IH),  22-4 3.82 (s, 6H), 5.78 (s, 1H), 7.25-7.60 (m, 5H), 7.88 (d IH), 8.05 (d, IH),
8.49(dd, IH)  8.49 (dd, IH)
25-11 2, 42(s, 3H), 3.76(s, 6H), 5.81(s, 1H 7.29(d, 2H), 7.34(dd, IH), 7.65  25-11 2, 42 (s, 3H), 3.76 (s, 6H), 5.81 (s, 1H 7.29 (d, 2H), 7.34 (dd, IH), 7.65
(d 1H),7.77(d, 2H),7.78(s 1H),8.43(dd, IH)  (d 1H), 7.77 (d, 2H), 7.78 (s 1H), 8.43 (dd, IH)
2.45(s, 3H 3.83(s, 6H), 5.85(s, IH), 5.88(d, IH), 6.33(d, 1H 7.02 (d lH),7.34(d, 2H), 7.39(dd, 1H),7.60(s IH), 7.81 (d, 2H), 8.49(dd, IH) 本発明化合物又はその塩は、 畑作条件で、 土壌処理、 茎葉処理のいずれの方法 でも高い除草活性を示す。 特に茎葉散布処理で、 メヒシバ、 カャッリグサ、 イチ ビ、 ィヌビュ等の各種の畑雑草に高い効力を示し、 トウモロコシ、 ムギ、 大豆、 ヮタ等の作物に選択性を示す化合物も含まれている。 2.45 (s, 3H 3.83 (s, 6H), 5.85 (s, IH), 5.88 (d, IH), 6.33 (d, 1H 7.02 (d lH), 7.34 (d, 2H), 7.39 (dd, 1H) , 7.60 (s IH), 7.81 (d, 2H), 8.49 (dd, IH) The compound of the present invention or a salt thereof exhibits a high herbicidal activity under any conditions of upland cropping in any of soil treatment and foliage treatment. In particular, foliar spray treatment has a high efficacy against various field weeds such as mexican, california, strawberry, and inubu, and also contains compounds that have selectivity for crops such as corn, wheat, soybeans, and ivy.
本発明化合物又はその塩は、 水田雑草のノビエ、 タマガヤッリ、 ォモダカ、 ホ 夕ルイ等の雑草に対し、 優れた殺草効力を有し、 イネに選択性を示す化合物も含 まれている。  The compound of the present invention or a salt thereof has an excellent herbicidal activity against weeds such as paddy field weeds such as Nobie, Tamagayari, Omodaka and Houyui, and also includes a compound showing selectivity to rice.
また本発明化合物又はその塩は、 果樹園、 芝生、 線路端、 空き地等の雑草の防 除にも適用することが出来る。  The compound of the present invention or a salt thereof can also be applied to the control of weeds in orchards, lawns, track ends, vacant lots and the like.
更に本発明化合物又はその塩には植物生長調節作用を有するものも含まれる。 本発明除草剤は、 前記一般式 〔 1〕 で示される化合物もしくはその塩の 1又は 2以上を有効成分として含有し、 通常の農薬と同様の形態を有する。 即ち、 有効 成分化合物は一般に適当な量を担体と混合して水和剤、 乳剤、 粒剤、 水溶剤、 フ ロアブル剤等の形に製剤化して使用される。 固体担体としてはタルク、 ホワイ ト カーボン （シリ力） 、 ベン卜ナイ ト、 クレイ、 ケイソゥ土等が挙げられ、 液体担 体としては、 水、 アルコール、 ベンゼン、 キシレン、 ケロシン、 鉱油、 シクロへ キサン、 シクロへキサノン、 ジメチルホルムアミ ド等が用いられる。 これらの製 剤に於て、 均一かつ安定な形態を取るために必要ならば、 界面活性剤を添加する こともできる。  Further, the compound of the present invention or a salt thereof includes those having a plant growth regulating action. The herbicide of the present invention contains one or more of the compound represented by the general formula [1] or a salt thereof as an active ingredient, and has a form similar to that of a general pesticide. That is, the active ingredient compound is generally used in the form of a wettable powder, an emulsion, a granule, a water solvent, a flowable or the like by mixing an appropriate amount with a carrier. Examples of the solid carrier include talc, white carbon (silicone force), bentonite, clay, and diatomaceous earth. Examples of the liquid carrier include water, alcohol, benzene, xylene, kerosene, mineral oil, cyclohexane, and the like. Cyclohexanone, dimethylformamide and the like are used. In these preparations, a surfactant may be added if necessary to obtain a uniform and stable form.
本発明除草剤における有効成分濃度は前述した製剤の形により種々の濃度に変 化するものであるが、 例えば、 水和剤に於いては、 5 ~ 9 0 %、 好ましくは 1 0 〜 8 5 % ：乳剤に於いては、 3 ~ 7 0 %、 好ましくは 5〜 3 0 %：粒剤に於いて は、 0 . 0 1〜 3 0 %、 好ましくは、 0 . 0 5 ~ 1 0 %の濃度が用いられる。 このようにして得られた水和剤、 乳剤は水で所定の濃度に希釈して懸濁液或は 乳濁液として、 粒剤はそのまま雑草の発芽前又は発芽後に散布処理もしくは混和 処理される。 実際に本発明除草剤を適用するに当たっては 1 0アール当り有効成 分 0 . 1 g以上の適当量が施用される。 又、 本発明除草剤は公知の殺菌剤、 殺虫剤、 殺ダニ剤、 除草剤、 植物成長調整 剤等と混合して使用することも出来る。 特に、 除草剤と混合使用することにより、 使用薬量を減少させることが可能である。 又、 省力化をもたらすのみならず、 混 合薬剤の相乗作用により一層高い効果も期待できる。 その場合、 複数の公知除草 剤との組合せも可能である。 本発明除草剤と混合使用するにふさわしい薬剤とし ては、 ベンチォカーブ、 モリネー ト、 ジメ ピぺレー ト等のカーバメィ ト系除草剤、 チォカーバメィ ト系除草剤、 ブタクロール、 プレチラクロール、 メフエナセッ ト 等の酸アミ ド系除草剤、 クロメ トキシニル、 ビフヱノ ックス等のジフエ二ルェ一 テル系除草剤、 ア トラジン、 シアナジン等のト リアジン系除草剤、 クロルスルフ ロン、 スルホメチュロン一メチル等のスルホニルゥレア系除草剤、 M C P， M C P B等のフユノキシアル力ンカルボン酸系除草剤、 ジクロホップ—メチル等のフ エノキシフエノキシプロピオン酸系除草剤、 フルアジホップブチル等のピリ ジル ォキシフヱノキシプロピオン酸系除草剤、 ベンゾィルプロップェチル、 フランプ 口ップェチル等のベンゾィルァミ ノプロピオン酸系除草剤、 イマザキン等のィ ミ ダゾリ ノ ン系除草剤、 その他として、 ピぺロホス、 ダイムロン、 ベン夕ゾン、 ダ イフェンゾコー ト、 ナブロアニリ ド、 H W— 5 2 ( 4 —エトキシメ トキシベンズ 一 2， 3 —ジクロルァニライ ド） 、 ト リァゾフエナミ ド、 キンク口ラック、 更に、 セ トキシジム、 ァロキシジム—ソディ ゥム等のシクロへキサンジオン系の除草剤 等が挙げられる。 又、 これらの組み合わせた物に植物油及び油濃縮物を添加する ことも出来る。 The active ingredient concentration in the herbicide of the present invention varies depending on the form of the preparation described above. For example, in the case of a wettable powder, it is 5 to 90%, preferably 10 to 85%. %: 3 to 70%, preferably 5 to 30% in the emulsion: 0.01 to 30%, preferably 0.05 to 10% in the granule The concentration is used. The wettable powder and emulsion thus obtained are diluted with water to a predetermined concentration to form a suspension or emulsion, and the granules are directly sprayed or mixed before or after germination of the weeds. . In actually applying the herbicide of the present invention, an appropriate amount of 0.1 g or more of the effective component per 10 ares is applied. The herbicide of the present invention can also be used by mixing with known fungicides, insecticides, acaricides, herbicides, plant growth regulators and the like. In particular, it is possible to reduce the amount of drug used by mixing and using herbicides. In addition to saving labor, higher effects can be expected due to the synergistic action of the mixed drug. In that case, a combination with a plurality of known herbicides is also possible. Suitable agents to be used in combination with the herbicide of the present invention include acid amides such as carbamate herbicides such as benthiocarb, molinate and dimepirate, tiocarbamate herbicides, butachlor, pretilachlor, mefenacet and the like. Herbicides, diphenyl ether herbicides such as chrometoxynil and bifenox; triazine herbicides such as atrazine and cyanadine; sulfonylurea herbicides such as chlorsulfuron and sulfometurone monomethyl; MCP, MCPB Carboxylic acid-based herbicides such as diclohop-methyl, etc., phenoxyphenoxypropionic acid-based herbicides such as diclohop-methyl, and pyridyloxy-benzooxypropionic acid-based herbicides such as fluazifop-butyl, and benzoylprop Benzyl, etc. Minopropionic acid herbicides, imidazoline and other imidazolinone herbicides, and other products such as piperophos, dimelone, benzozone, difenzocoat, nabroanilide, and HW-52 (4-ethoxyethoxybenz-1) 2,3-Dichloranilide), triazophenamide, kink-mouth lac, and cyclohexanedione-based herbicides such as sethoxydim and aroxydim-sodium. Vegetable oils and oil concentrates can also be added to these combinations.
次に、 本発明除草剤に関する製剤例を若干示すが、 有効成分化合物、 添加物及 び添加割合は、 本実施例にのみ限定されることなく、 広い範囲で変更可能である ( 実施例 2 7 水和剤 Next, some formulation examples of the herbicide of the present invention are shown, but the active ingredient compounds, additives and the addition ratio can be changed in a wide range without being limited only to this example ( Example 27). Wettable powder
本発明化合物 2 0部  Compound of the present invention 20 parts
ホワイ トカーボン 2 0部  White carbon 20 parts
ケイソゥ土 5 2部  Diatomaceous earth 5 2 parts
アルキル硫酸ソーダ 8部 以上を均一に混合、 微細に粉碎して、 有効成分 2 0 %の水和剤を得た。 Sodium alkyl sulfate 8 parts The above components were uniformly mixed and finely pulverized to obtain a 20% wettable powder of the active ingredient.
実施例 2 8 乳剤 Example 28 Emulsion
本発明化合物 2 0部  Compound of the present invention 20 parts
キシレン 5 5部  Xylene 5 5 parts
ジメチルホルムァミ ド 1 5部  Dimethylformamide 15 parts
ポリオキシエチレンフヱニルエーテル 1 0部  Polyoxyethylene phenyl ether 10 parts
以上を混合、 溶解して有効成分 2 0 %の乳剤を得た。  The above ingredients were mixed and dissolved to obtain an emulsion containing 20% of the active ingredient.
実施例 2 9 粒剤 Example 2 9 granules
本発明化合物 5部  5 parts of the compound of the present invention
タルク 4 0部  Talc 40 parts
ク レー 3 8部  Cray 3 8 copies
ベントナイ ト 1 0部  Bentonite 10 parts
アルキル硫酸ソーダ 7部  Sodium alkyl sulfate 7 parts
以上を均一に混合して微細に粉砕後、 直径 5〜 1. 0 mmの粒状に造粒し て有効成分 5 %の粒剤を得た。 産業上の利用可能性：  The above mixture was uniformly mixed and finely ground, and then granulated into granules having a diameter of 5 to 1.0 mm to obtain granules having an active ingredient of 5%. Industrial applicability:
次に本発明除草剤の効果に関する試験例を示す。  Next, test examples relating to the effect of the herbicide of the present invention will be shown.
試験例 1 茎葉散布処理 Test Example 1 Foliage application
2 0 0 c m2 のポッ トに土壌を充塡し、 表層にメ ヒシバ、 力ャッリグサ、 ィヌ ビュの各種子を播き、 軽く覆土後温室内で生育させた。 各雑草が 5~ 1 0 c mの 草丈に生育した時点で各供試化合物の乳剤を水で希釈して調整した 4 0 0 0 p p mの薬液を 1 0 0 1ノ 1 0 aの割合 （ 1 0 a当り 4 0 0 g相当） で小型噴霧器に て雑草の茎葉部に散布した。 3週間後に雑草の除草効果を下記の調査基準に従つ て調査し、 その結果を以下の表 3 2に示した。 調査基準 The soil was filled in a pot of 200 cm 2 , and seedlings of Meishishiba, Karyarigusa and Inubu were sown on the surface layer, and after lightly covering the soil, they were grown in a greenhouse. When each weed grew to a height of 5 to 10 cm, the emulsion of each test compound was diluted with water and adjusted to a concentration of 400 ppm. (equivalent to 400 g per a) and sprayed on the foliage of weeds with a small sprayer. Three weeks later, the weed herbicidal effect was investigated according to the following criteria, and the results are shown in Table 32 below. Survey criteria
殺 草 率 殺草指数  Weed kill rate Weed kill index
0 % 0  0% 0
2 0 ~ 2 9 % 2  2 0 ~ 2 9% 2
4 0~4 9 % 4  4 0 ~ 4 9% 4
6 0-69% 6  6 0-69% 6
80〜 89 % 8  80-89% 8
1 00 % 1 0  1 00% 10
又、 1 , 3, 5 7 9の数値は、 各々 0と 2 2と 4， 4と 6， 6と 8, 8 と 1 0の中間の値を示す c  The numbers 1, 3, 5 7 9 represent the intermediate values between 0, 22, and 4, 4 and 6, 6, 6, 8, 8, and 10, respectively.
(無処理区の地上部生草重 -処理区の地上部生草重） 殺草率 （％) X 1 00 無処理区の地上部生草重 (Aboveground fresh grass weight in untreated area-Aboveground fresh grass weight in treated area) Herbicidal rate (%) X 100 Above-ground fresh grass weight in untreated area
第 32 表 Table 32
数  number
No. メ ヒシ 力ャッリ グサ ィ ヌ ビュ-13 9 10 9 - 11 10 10 10-1 10 10 10 - 8 9 10 9-56 10 10 10-71 10 10 10-95 10 10 10-110 10 10 10-115 9 10 10-135 10 10 10-137 10 10 10-10 8 10 10-6 10 10 10  No.Mechanical Power Signal -13 9 10 9-11 10 10 10 -1 10 10 10-8 9 10 9-56 10 10 10-71 10 10 10-95 10 10 10-110 10 10 10 -115 9 10 10-135 10 10 10-137 10 10 10-10 8 10 10-6 10 10 10

Claims

請求の範囲 The scope of the claims
1. 一般式 〔 1〕  1. General formula [1]
Figure imgf000096_0001
Figure imgf000096_0001
〔式中、 Aは窒素原子、 もしく は R3 で置換された炭素原子を表し、 Wherein A represents a nitrogen atom or a carbon atom substituted by R 3 ;
Bは窒素原子、 又は水素もしく は Xで置換された炭素原子を表し、  B represents a nitrogen atom or a carbon atom substituted by hydrogen or X;
Zは酸素、 酸化されていても良い硫黄、 置換されていても良い窒素、 又は置換 されていても良い炭素原子を表し、  Z represents oxygen, optionally oxidized sulfur, optionally substituted nitrogen, or optionally substituted carbon atom,
Qは窒素、 酸素もしく は硫黄を 1〜4個含む 5~6員の複素環を表し、 かつ Q の炭素原子でベンゼン環もしくはピリ ジン環部と結合しており、  Q represents a 5- to 6-membered heterocyclic ring containing 1 to 4 nitrogen, oxygen or sulfur, and is bonded to the benzene or pyridyl ring at the carbon atom of Q;
R！ , R2 は各々独立して水素、 C!— 4 アルキル、 Cい 4 アルコキシ、 d- 4 ハロアルコキシ、 ハロアルキル、 C l - 4 アルキルァミ ノ、 ジ d-4 アルキ ルァミ ノ、 C ,-4 アルキルチオ、 ハロゲン、 シァノ基を表し、 R! , R 2 are each independently hydrogen, C -! 4 alkyl, C physician 4 alkoxy, d-4 haloalkoxy, haloalkyl, C l - 4 Arukiruami Bruno, di d-4 alkyl Ruami Roh, C, - 4 alkylthio, Represents a halogen or cyano group,
R3 は水素、 C】-4 アルキル、 ハロゲン、 ニトロ、 ホルミル、 ァシル基を表し、 又、 R2 と R3 は一緒になつて環を形成していても良く、 R 3 is hydrogen, C] - 4 represents alkyl, halogen, nitro, formyl, a Ashiru group, and, R 2 and R 3 may form a connexion ring such together,
X, Yは各々独立して水素、 C i アルキル、 C3- シクロアルキル、 C2-S ァ ルケニル、 ハロアルキル、 C2-6 アルキニル、 ハロゲン、 ニトロ、 ァミ ノ、 C アルキルァミ ノ、 ァシルァミ ノ、 C !-6 アルキルスルホニルァミ ノ、 ホル ミル、 ァシル、 シァノ、 カルボキシル、 ィ ミ ノ、 ヒ ドロキシル、 C !-6 アルコキ シカルボニル、 6 アルコキシ、 置換されても良いベンジルォキシ、 C2- 6 Ύ ルケニルォキシ、 d- 6 ハロアルコキシ、 C2-6 アルキニルォキシ、 置換されて も良いフエノキシ、 置換されても良いベンジル、 アミ ノォキシ、 C i— 6 アルキル チォ、 置換されても良いフヱニル、 d アルキルスルホニル、 置換されても良 いフエ二ルチオ、 C2-6 アルケニルチオ、 C2_6 アルキニルチオ、 置換されても 良いベンゾィル、 置換されても良いフヱニルスルホニル、 又は置換されても良い ヘテロ環—ォキシおよびへテロ環—チォ基を表し、 X, Y are each independently hydrogen, C i alkyl, C 3 - cycloalkyl, C 2 - S § alkenyl, haloalkyl, C 2 - 6 alkynyl, halogen, nitro, § Mi Roh, C Arukiruami Bruno, Ashiruami Bruno, C -! 6 alkylsulfonyl § Mi Bruno, formyl, Ashiru, Shiano, carboxyl, I Mi Bruno, human Dorokishiru, C -! 6 an alkoxy carbonyl, 6 alkoxy, may be substituted Benjiruokishi, C 2 - 6 Ύ Rukeniruokishi , d-6 haloalkoxy, C 2 - 6 Arukiniruokishi, which may be substituted phenoxy, an optionally substituted benzyl, amino Nookishi, C i-6 alkyl Chio, which may be substituted Fuweniru, d alkylsulfonyl, be substituted have good phenylene thioether, C 2 - 6 alkenylthio, C 2 _ 6 alkynylthio, an optionally substituted Benzoiru, substituted There off We sulfonyl sulfonyl, or may be substituted Represents a heterocyclic-oxy and heterocyclic-thio group,
又、 2つ Xもしくは 2つの Yで炭素環、 又は複素環を形成してもよく m, nは 1〜4の整数を表す。 〕 で表される複素環誘導体及びその塩。  Also, two Xs or two Ys may form a carbocyclic or heterocyclic ring, and m and n represent an integer of 1 to 4. ] The heterocyclic derivative represented by these, and its salt.
2. Q— Yn力  2. Q—Yn force
0
Figure imgf000097_0001
0
Figure imgf000097_0001
J 54 Y 55 J 54 Y 55
N =^ N二  N = ^ N two
N 0 N' S  N 0 N 'S
または  Or
〔式中、 Y, ~Υ55は水素、 d-6 アルキル、 C3 - 7 シクロアルキル、 C2- アルケニル、 （ 卜 ハロアルキル、 C2- 6 アルキニル、 ハロゲン、 ニトロ、 アミ ノ、 d アルキルァミ ノ、 ァシルァミ ノ、 C!-6 アルキルスルホニルァミ ノ、 ホルミル、 ァシル、 シァノ、 カルボキシル、 ィ ミ ノ、 ヒ ドロキシル、 アル コキシカルボニル、 d アルコキシ、 置換されても良いベンジルォキシ、 C2一 f アルケニルォキシ、 C!- ハロアルコキシ、 C2- 6 アルキニルォキシ、 置換され ても良いフヱノキシ、 置換されても良いベンジル、 アミ ノォキシ、 アルキ ルチオ、 置換されても良いフヱニル、 アルキルスルホニル、 置換されても 良いフエ二ルチオ、 C2- アルケニルチオ、 C2- e アルキニルチオ、 置換されて も良いベンゾィル、 置換されても良いフヱニルスルホニル、 又は置換されても良 いへテロ環一ォキシおよびへテロ環一チォ基を表し、 Wherein, Y, ~ Υ 55 is hydrogen, d-6 alkyl, C 3 - 7 cycloalkyl, C 2 - Alkenyl, (Bok haloalkyl, C 2 - 6 alkynyl, halogen, nitro, amino, d Arukiruami Bruno, Ashiruami Bruno, C -! 6 alkylsulfonyl § Mi Bruno, formyl, Ashiru, Shiano, carboxyl, I Mi Bruno, human Dorokishiru , alkoxide aryloxycarbonyl, d alkoxy, which may be substituted Benjiruokishi, C 2 one f Arukeniruokishi, C -! haloalkoxy, C 2 - 6 Arukiniruokishi, which may be substituted Fuwenokishi may be substituted benzyl, Ami Nookishi, alkyl thio, may be substituted Fuweniru, alkylsulfonyl, an optionally substituted phenylene thioether, C 2 - alkenylthio, C 2 - e alkynylthio, an optionally substituted Benzoiru, substituted Phenylsulfonyl, or an optionally substituted heterocycle It represents B ring one Chio group,
又、 2つの Υ, ~Y55で炭素環、 又は複素環を形成してもよい。 〕 である請求 項 1記載の複素環誘導体及びその塩。 Also, two Upsilon, may form a carbon ring ~ Y 55, or a heterocyclic ring. The heterocyclic derivative according to claim 1, and a salt thereof.
3. Q— Υη 力く、
Figure imgf000098_0001
3. Q— Υ η power,
Figure imgf000098_0001
〔式中、 ： は単結合または二重結合を表し、 [In the formula, represents a single bond or a double bond,
D！ が Nの時は、 D2 は NY又は 0を表し、 D! When is N, D 2 represents NY or 0,
D が NYの時は、 D2 は CYを表し、 When D is NY, D 2 represents CY,
D が 0の時は、 D2 は Nを表し、 When D is 0, D 2 represents N,
Y及び nは前記と同じ意味を表す。 〕 である請求項 1記載の複素環誘導体 及びその塩。  Y and n have the same meaning as described above. 2. The heterocyclic derivative according to claim 1, which is or a salt thereof.
4. Qが、 ォキサゾールー 5—ィル又は 2—ォキサゾリ ン— 5—ィル基である請 求項 1記載の複素環誘導体及びその塩。 4. The heterocyclic derivative according to claim 1, wherein Q is an oxazole-5-yl or 2-oxazoline-5-yl group, and a salt thereof.
5. 一般式 〔2〕 5. General formula [2]
し ,Ri R2 , Ri R 2
〔2〕  [2]
〔式中、 R, , R2 , Aは前記と同じ意味を表し、 Lは脱離基を表す。 〕 で表 される化合物と、 一般式 〔3〕 [Wherein, R,, R 2 and A have the same meaning as described above, and L represents a leaving group. And a compound represented by the general formula (3):
Figure imgf000099_0001
Figure imgf000099_0001
Xm  Xm
〔3〕  [3]
〔式中、 B， Q, X， Y, m, ηは前記と同じ意味を表す。 〕 で表される化合 物を力ップリングさせる事を特徴とする一般式 〔4〕  [Wherein, B, Q, X, Y, m, and η represent the same meaning as described above. The general formula [4] characterized in that the compound represented by
Figure imgf000099_0002
Figure imgf000099_0002
〔式中、 A， B， Q， R, , R2 , X, Y, m, ηは前記の意味を表す。 ：） で 表される化合物の製造方法。 [Where A, B, Q, R,, R 2 , X, Y, m, and η represent the above-mentioned meanings. :) A method for producing a compound represented by
6. 請求項 1、 請求項 2、 請求項 3または請求項 4記載の複素環誘導体もしくは その塩の 1種又は 2種以上を有効成分として含有することを特徴とする除草剤。  6. A herbicide comprising, as an active ingredient, one or more of the heterocyclic derivative or a salt thereof according to claim 1, 2, 3, or 4.
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