Information
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Patent Application
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20020032227
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Publication Number
20020032227
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Date Filed
December 04, 200023 years ago
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Date Published
March 14, 200222 years ago
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CPC
- C07D231/06 - having one double bond between ring members or between ring members and non-ring members
- A01N43/50 - 1,3-Diazoles Hydrogenated 1,3-diazoles
- C07D231/12 - with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D233/64 - with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D249/08 - 1,2,4-Triazoles Hydrogenated 1,2,4-triazoles
- C07D257/04 - Five-membered rings
- C07D261/08 - with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D263/10 - with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D263/32 - with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D271/06 - 1,2,4-Oxadiazoles Hydrogenated 1,2,4-oxadiazoles
- C07D271/10 - 1,3,4-Oxadiazoles Hydrogenated 1,3,4-oxadiazoles
- C07D277/10 - with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D285/06 - 1,2,3-Thiadiazoles Hydrogenated 1,2,3-thiadiazoles
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US Classifications
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International Classifications
- C07D249/08
- A61K031/4196
- A61K031/4164
Abstract
A compound represented by general formula (I) or a salt thereof, a process for producing the same, an intermediate for the production thereof, and a bactericide (fungicide) containing the same as the active ingredient wherein R1 represent optionally substituted aryl, optionally substituted heterocycle, mono- or di-substituted methyleneamino, optionally substituted (substituted imino)methyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, substituted carbonyl or substituted sulfonyl; R2 represents alkyl, alkenyl, alkynyl or cycloalkyl; R3 represents optionally substituted heterocycle; R4 represents hydrogen, alkyl, alkoxy, halogen, nitro, cyano or haloalkyl; M represents oxygen, S(O)i (i being 0, 1 or 2), NR16 (R16 being hydrogen, alkyl or acyl) or a single bond; n represents 0 or 1, provided n represent 1 when R3 represents imidazol-1-yl or 1H-1,2,4-triazol-1-yl; and the symbol˜represents the E form, Z form or a mixture thereof.
Description
TECHNICAL FIELD
[0001] The present invention relates to an oxime derivative, particularly a heterocyclic compound substituted with α-(O-substituted oxyimino)-2-substituted benzyl, a process for producing it, intermediates therefor, and a bactericide (fungicide) containing it as an active ingredient.
BACKGROUND ART
[0002] Compounds containing α-(O-substituted oxyimino)-benzyl known so far include benzohydroxymoylazole derivatives having insecticidal activity (JP-A 1-308260, JP-A 5-1046, WO92/09581, JP-A 5-331011, JP-A 5-331012, JP-A 6-41086), oxime derivatives having insecticidal activity (JP-A 3-68559), 1-azolyl-substituted oxime ethers having fungicidal activity (JP-A 60-87269), etc.
[0003] The present invention is to provide a compound having more potent fungicidal activity, higher utility, etc., than the known compounds as well as low toxicity.
DISCLOSURE OF INVENTION
[0004] The present inventors have intensively studied to achieve the above object. As a result, it has been found that a heterocyclic compound substituted with α-(O-substituted oxyimino)-2-substituted benzyl has potent fungicidal activity. After further studies, the present invention has been completed.
[0005] The present invention provides:
[0006] 1. A compound of the formula (I):
1
[0007] wherein R1 is optionally substituted aryl, an optionally substituted heterocyclic group, mono or disubstituted methyleneamino, optionally substituted (substituted imino)methyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, substituted carbonyl or substituted sulfonyl; R2 is alkyl, alkenyl, alkynyl or cycloalkyl; R3 is an optionally substituted heterocyclic group; R4 is hydrogen, alkyl, alkoxy, halogen, nitro, cyano or halogenated alkyl; M is an oxygen atom, S(O)i (in which i is 0, 1 or 2), NR16 (in which R16 is hydrogen, alkyl or acyl) or a single bond; n is 0 or 1, provided that, when R3 is imidazol-1-yl or 1H-1,2,4-triazol-1-yl, n is 1; and˜indicates an E- or Z-isomer or a mixture thereof; or a salt thereof;
[0008] 2. A compound according to the above item 1, wherein the optionally substituted heterocyclic group represented by R1 is pyridyl, pyrimidinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, pyridazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, triazolyl, quinolyl, indolyl, benzisothiazolyl, benzisoxazolyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof;
[0009] 3. A compound according to the above item 1, wherein R1 is phenyl or a heterocyclic group, each of which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro, or a salt thereof;
[0010] 4. A compound according to the above item 1, wherein R1 is phenyl; phenyl substituted with halogen and/or lower alkyl; or pyridyl substituted with halogen and/or halogenated lower alkyl; or a salt thereof:
[0011] 5. A compound according to the above item 1, wherein R1 is phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 4-chloro-2-methylphenyl, 2-chloropyridin-3-yl, 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl or 3-trifluoromethyl-5-chloropyridin-2-yl, or a salt thereof;
[0012] 6. A compound according to the above item 1, wherein R1 is a group of the formula (a):
2
[0013] wherein R9 and R10 are the same or different and are hydrogen, optionally substituted alkyl, acyl, alkylthio, alkylsulfinyl alkylsulfonyl, optionally substituted amino, cycloalkyl, optionally substituted aryl or an optionally substituted heterocyclic group, or R9 and R10 are linked together to form a monocyclic or polycyclic ring which may contain a heteroatom, or a salt thereof;
[0014] 7. A compound according to the above item 1, wherein R9 and R10 are the same or different and are hydrogen, alkyl, haloalkyl, alkoxyalkyl, alkylcarbonyl, optionally substituted phenyl, optionally substituted naphthyl or an optionally substituted heterocyclic group, or R9 and R10 are linked together to form a cyclopentane or cyclohexane ring which may form a condensed ring with another ring, or a salt thereof;
[0015] 8. A compound according to the above item 1, wherein R9 is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl and cyano, or a salt thereof;
[0016] 9. A compound according to the above item 1, wherein R9 is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of chlorine, methyl, trifluoromethyl and methoxy, or a salt thereof;
[0017] 10. A compound according to the above item 1, wherein R9 is morpholino, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof;
[0018] 11. A compound according to the above item 1, wherein R10 is hydrogen or alkyl, or a salt thereof;
[0019] 12. A compound according to the above item 1, wherein R10 is hydrogen, methyl or ethyl, or a salt thereof;
[0020] 13. A compound according to the above item 1, wherein R2 is alkyl or alkenyl, or a salt thereof;
[0021] 14. A compound according to the above item 1, wherein R2 is methyl, ethyl or allyl, or a salt thereof;
[0022] 15. A compound according to the above item 1, wherein R3 is isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiazolinyl, isoxazolinyl, imidazolinyl, oxazolinyl or thiazolidinyl, each of which is unsubstituted or substituted, or a salt thereof;
[0023] 16. A compound according to the above item 1, wherein R3 is imidazolyl; imidazolyl substituted with lower alkyl; imidazolinyl; triazolyl; imidazolinyl substituted with lower alkyl; isoxazolyl; isoxazolyl substituted with lower alkyl; oxadiazolyl; oxadiazolyl substituted with lower alkyl; isoxazolinyl; isoxazolinyl substituted with lower alkyl; oxazolinyl; pyrazolyl; pyrazolyl substituted with lower alkyl; thiazolinyl; furyl; tetrazolyl substituted with lower alkyl; oxazolyl; isothiazolyl substituted with lower alkyl; thiazolidinyl; or thiazolidinyl substituted with lower alkyl; or a salt thereof;
[0024] 17. A compound according to the above item 1, wherein R3 is imidazol-1-yl, imidazol-2-yl, 1-methylimidazol-2-yl, 2-methylimidazol-1-yl, 4-methylimidazol-1-yl, 5-methylimidazol-1-yl, 2-imidazolin-2-yl, 1H-1,2,4-triazol-1-yl, 1-methyl-2-imidazolin-2-yl, isoxazol-3-yl, 3-methylisoxazol-5-yl, 5-methylisoxazol-3-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 2-isoxazolin-3-yl, 2-oxazolin-2-yl, 3-methyl-2-isoxazolin-5-yl, pyrazol-1-yl, 1-methylpyrazol-5-yl, 2-thiazolin-2-yl, 2-furyl, 3-methylisothiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 2-methyltetrazol-5-yl, oxazol-5-yl, isoxazol-5-yl, thiazolidin-2-yl or 3-methylthiazolidin-2-yl, or a salt thereof;
[0025] 18. A compound according to the above item 1, wherein R4 is hydrogen, or a salt thereof;
[0026] 19. A compound according to the above item 1, wherein M is an oxygen atom, or a salt thereof;
[0027] 20. A fungicidal composition comprising a compound according to any one of the above items 1 to 19 or a salt thereof as an active ingredient;
[0028] 21. A process for producing a compound of the formula (I):
3
[0029] wherein each symbol is as defined in the above item 1, which comprises reacting the compound of the formula (V):
4
[0030] wherein A is halogen and the other symbols are as defined in the above item 1, with a compound of the formula (X):
R3—H (X)
[0031] wherein R3 is an optionally substituted heterocyclic group;
[0032] 22. A process according to the above item 21, wherein R3 is pyrrolyl, imidazolyl, pyrazolyl or triazolyl, each of which is unsubstituted or substituted;
[0033] 23. A compound of the formula (V):
5
[0034] wherein A is halogen and the other symbols are as defined in the above item 1, or a salt thereof;
[0035] 24. A compound according to the above item 23, wherein M is an oxygen atom, or a salt thereof;
[0036] 25. A compound of the formula (XIV):
6
[0037] wherein each symbol is as defined in the above item 1, provided that, when M is an oxygen atom and R3 is isoxazol-4-yl, n is 1, or a salt thereof;
[0038] 26. A compound according to the above item 25, wherein M is an oxygen atom, or a salt thereof; and,
[0039] 27. A compound of the formula (XLVIII):
7
[0040] wherein P is a protective group of a hydroxyl group, and the other symbols are as defined in the above item 1, or a salt thereof.
[0041] The term “lower” used herein means having 1 to 8 carbon atoms, preferably 1 to 6 carbon atoms, more preferably 1 to 4 carbon atoms, unless otherwise indicated.
[0042] The aryl of the optionally substituted aryl represented by R1 includes aryl having 6 to 14 carbon atoms such as phenyl, naphthyl, etc.
[0043] The optionally substituted heterocyclic group represented by R1 includes unsubstituted or substituted heterocyclic groups. Examples of the heterocyclic group include 5- to 7-membered heterocyclic groups containing 1 to 4 heteroatoms selected from nitrogen, sulfur and oxygen in the ring, such as pyridyl (e.g., pyridin-2-yl, pyridin-3-yl), pyrimidinyl (e.g., pyrimidin-2-yl, pyrimidin-4-yl), benzoxazolyl (e.g., benzoxazol-2-yl), benzothiazolyl (e.g., benzothiazol-2-yl), benzimidazolyl, isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl), isothiazolyl, thiadiazolyl [e.g., 1,3,4-thiadiazolyl (e.g., 1,3,4-thiadiazol-2-yl), 1,2,4-thiadiazolyl, etc.], pyridazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl (e.g., 1,3,4-oxadiazolyl, 1,2,4-oxadiazolyl, etc.), triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl, etc.), quinolyl (e.g., quinolin-2-yl), indolyl, benzisothiazolyl, benzisoxazolyl, pyrazinyl (e.g., pyrazin-2-yl), etc. The heterocyclic group may form a condensed cyclic group with a carbocycle or another heterocycle. The heterocycle has a bond to M at any possible position in the ring.
[0044] The substituent of the substituted aryl and substituted heterocyclic group represented by R1 includes, for example, lower alkyl (e.g., methyl, ethyl, propyl, butyl, etc.), lower alkenyl (e.g., vinyl, allyl, crotyl, etc.), lower alkynyl (e.g., ethynyl, propargyl, butynyl, etc.), cycloalkyl (e.g., cyclopropyl, cyclopentyl, cyclohexyl, etc.), cycloalkenyl (e.g., cyclopentenyl, cyclohexenyl, etc.), lower alkanoyl (e.g., acetyl, propionyl, isobutyryl, etc.), lower alkylsilyl (e.g., methylsilyl, ethylsilyl, propylsilyl, butylsilyl, etc.), halogenated lower alkyl (e.g., trifluoromethyl, trichloromethyl, chloromethyl, 2-bromoethyl, 1,2-dichloropropyl, etc.), di(lower)alkylamino (e.g., dimethylamino, diethylamino, etc.), phenyl, phenyl(lower)alkyl (e.g., benzyl, phenethyl, etc.), phenyl(lower)alkenyl (e.g., styryl, cinnamyl, etc.), furyl(lower)alkyl (e.g., 3-furylmethyl, 2-furylethyl, etc.), furyl(lower)alkenyl (e.g., 3-furylvinyl, 2-furylallyl, etc.), halogen (e.g., fluorine, chlorine, bromine, iodine), nitro, cyano, lower alkylthio (e.g., methylthio, ethylthio, propylthio, etc.), —OR11 [wherein R11 is hydrogen, lower alkyl group (e.g., methyl, ethyl, propyl, etc.), lower alkenyl (e.g., vinyl, allyl, crotyl, etc.), lower alkynyl (e.g., ethynyl, 2-propynyl, 3-butynyl, etc.), lower alkanoyl (e.g., acetyl, propionyl, butyryl, etc.), phenyl, lower alkoxyphenyl (e.g., 3-methoxyphenyl, 4-ethoxyphenyl, etc.), nitrophenyl (e.g., 3-nitrophenyl, 4-nitrophenyl, etc.), phenyl(lower)alkyl (e.g., benzyl, phenethyl, phenylpropyl, etc.), cyanophenyl(lower)alkyl (e.g., 3-cyanophenylmethyl, 4-cyanophenylethyl, etc.), benzoyl, tetrahydropyranyl, pyridyl, trifluoromethylpyridyl, pyrimidinyl, benzothiazolyl, quinolyl, benzoyl(lower)alkyl (e.g., benzoylmethyl, benzoylethyl, etc.), benzensulfonyl, or lower alkylbenzenesulfonyl (e.g., toluenesulfonyl, etc.)], —CH2—Z—R12 [wherein Z is —O—, —S— or —NR13— (in which R13 is hydrogen or lower alkyl), R12 is phenyl, halophenyl (e.g., 2-chlorophenyl, 4-fluorophenyl, etc.), lower alkoxyphenyl (e.g., 2-methoxyphenyl, 4-ethoxyphenyl, etc.), pyridyl, or pyrimidinyl], etc. In particular, halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro are preferred. More preferred are halogen and lower alkyl. The substituent may be at any possible position in the ring. The number of the substituent(s) is 1 to 5, preferably 1 to 4, more preferably 1 to 3. The substituents may be the same or different.
[0045] R1 is preferably phenyl or a heterocyclic group each of which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro. Preferred examples of R1 include phenyl, phenyl substituted with halogen (preferably chlorine) and/or lower alkyl (preferably methyl) (e.g., 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 4-chloro-2-methylphenyl, etc.), pyridyl substituted with halogen (preferably chlorine) and/or halogenated lower alkyl (preferably trifluoromethyl) (e.g., 2-chloropyridin-3-yl, 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl, 3-trifluoromethyl-5-chloropyridin-2-yl, etc.), etc.
[0046] Mono or disubstituted methyleneamino is also preferred for R1. The mono or disubstituted methyleneamino is represented, for example, by the above formula (a). The alkyl of the optionally substituted alkyl represented by R9 or R10 in the formula (a) includes, for example, alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc. In particular, methyl or ethyl is preferred. Examples of the substituted alkyl include haloalkyl containing as the substituent at least one halogen (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine) (e.g., difluoromethyl, trifluoromethyl, chloromethyl, 2-bromoethyl, 2,3-dichloropropyl, etc.); alkoxyalkyl containing as the substituent alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.) (e.g., methoxymethyl, ethoxymethyl, methoxyethyl, etc.); etc. In particular, trifluoromethyl is preferred for the haloalkyl, and methoxymethyl is preferred for the alkoxyalkyl.
[0047] The acyl represented by R9 or R10 includes, for example, alkylcarbonyl, arylcarbonyl, etc. Examples of the alkylcarbonyl includes C1-6 alkylcarbonyl, preferably C1-4 alkylcarbonyl, such as acetyl, trifluoroacetyl, propionyl, butyryl, etc. Examples of the arylcarbonyl include C6-14 arylcarbonyl such as benzoyl, naphthoyl, etc.
[0048] The alkyl of the alkylthio, alkylsulfinyl and alkylsulfonyl represented by R9 or R10 includes the above alkyl of the optionally substituted alkyl represented by R9 or R10.
[0049] The optionally substituted amino represented by R9 R10 includes, for example, amino, amino mono or disubstituted with alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., monomethylamino, dimethylamino, monoethylamino, etc.), amino monosubstituted with formyl, amino monosubstituted with alkylcarbonyl having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms (e.g., methylcarbonylamino, etc.), etc.
[0050] The cylcloalkyl represented by R9 or R10 includes cycloaklyl having 3 to 7 carbon atoms, preferably 5 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc.
[0051] The optionally substituted aryl represented by R9 or R10 includes, for example, C6-14 aryl such as phenyl, naphthyl (e.g., 1-naphthyl, etc.), fluorenyl, etc. In particular, phenyl is preferred. The aryl may be substituted at any possible position in the group. The number of the substituent(s) is 1 to 3. Examples the substituent include halogen, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl, cyano, etc.
[0052] Examples of the halogen as the substituent of the optionally substituted aryl represented by R9 or R10 include fluorine, chlorine, bromine, and iodine.
[0053] Examples of the optionally substituted alkyl as the substituent of the optionally substituted aryl represented by R9 or R10 include the optionally substituted alkyl represented by R1 described hereinafter. Of them, alkyl or haloalkyl, in particular methyl or trifluoromethyl, is preferred.
[0054] Examples of the optionally substituted hydroxyl as the substituent of the optionally substituted aryl represented by R9 or R10 include hydroxyl, alkoxy, alkenyloxy, alkynyloxy, haloalkoxy, aryloxy, etc. The alkoxy includes, for example, alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, butoxy, etc. In particular, methoxy is preferred. The alkenyloxy includes, for example, alkenyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as vinyloxy, allyloxy, crotyloxy, etc. In particular, allyloxy is preferred. The alkynyloxy includes, for example, alkynyloxy having 2 to 8 carbon atoms, preferably 2 to 4 carbon atoms, such as ethynyloxy, propargyloxy, butynyloxy, etc. In particular, propargyloxy is preferred. The haloalkoxy includes alkoxy described above which is substituted with at least one halogen (e.g., fluorine, chlorine, bromine iodine) such as difluoromethoxy, trifluoromethoxy, chloromethoxy, etc. In particular, difluoromethoxy is preferred. The aryloxy includes, aryloxy having 6 to 12 carbon atoms, preferably 6 to 8 carbon atoms, such as phenoxy, naphthoxy, etc.
[0055] Examples of the alkylthio as the substituent of the optionally substituted aryl represented by R9 or R10 include alkylthio having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, more preferably 1 to 2 carbon atoms, such as methylthio, ethylthio, propylthio, butylthio, etc. In particular, methylthio is preferred.
[0056] Examples of the optionally substituted amino as the substituent of the optionally substituted aryl represented by R9 or R10 include amino, amino mono or disubstituted with alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., monomethylamino, dimethylamino, monoethylamino, etc.), etc.
[0057] The optionally substituted heterocyclic group represented by R9 or R10 includes, for example, heterocyclic groups containing 1 to 4, preferably 1 to 2 heteroatoms (e.g., oxygen, nitrogen, sulfur, etc.) in the ring. At any possible position in the ring, the heterocyclic group contains the bond to the methylene carbon atom in the formula (a). Examples of the heterocyclic group include morpholinyl, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl, pyrazinyl, etc. In particular, morpholinyl (e.g., morpholino, etc.), furyl (e.g., 2-furyl, etc.), thienyl (e.g., 2-thienyl, etc.), pyridyl (e.g., 2-pyridyl, etc.), pyrazinyl (e.g., 2-pyrazinyl, etc.), or pyrimidinyl (e.g., 2-pyrimidinyl, etc.) is preferred. The heterocyclic group is unsubstituted or substituted. Examples of the substituent include the above substituents of the optionally substituted aryl represented by R9 or R10.
[0058] The monocyclic or polycyclic ring which may contain a heteroatom and is formed by R9 and R10 is a 4 to 8 membered ring which is formed by R9 and R10 together with the carbon atom to which R9 and R10 are attached and which may contain at least one heteroatom (e.g., oxygen, nitrogen, sulfur, etc.). The ring may form a condensed ring with another ring. Examples of the monocyclic or polycyclic ring include cyclopentane, cyclohexane, indan, 1,2,3,4-tetrahydronaphthalene, 5,6,7,8-tetrahydroquinoline, 4,5,6,7-tetrahydrobenzo[b]furan, etc. At any possible position in the ring, the monocyclic or polycyclic ring contains the bivalent bond to the methyleneamino nitrogen atom.
[0059] R9 is preferably phenyl unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen (preferably chlorine), optionally substituted alkyl [e.g., alkyl (preferably in particular methyl), haloalkyl (preferably trifluoromethyl), alkoxyalkyl, etc.], optionally substituted hydroxyl [e.g., hydroxyl, alkoxy (preferably methoxy), alkenyloxy, alkynyloxy, haloalkoxy, aryloxy, etc.], alkylthio, optionally substituted amino, nitro, phenyl and cyano; or morpholino, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl or pyrazinyl, each of which is unsubstituted or substituted.
[0060] R10 is preferably hydrogen or alkyl (preferably methyl or ethyl).
[0061] The optionally substituted (substituted imino)methyl represented by R1 is represented, for example, by the formula (b):
8
[0062] wherein R14 and R15 have the same meanings as the above R10 and R9, respectively.
[0063] The optionally substituted alkyl represented by R1 includes, for example, alkyl having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, etc. In particular, methyl and ethyl are preferred. The substituted alkyl includes, for example, haloalkyl containing as the substituent at least one halogen atom (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine) (e.g., difluoromethyl, trifluoromethyl, chloromethyl, 2-bromoethyl, 2,3-dichloropropyl, etc.); alkoxyalkyl groups containing as the substituent alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.) (e.g., methoxymethyl ethoxymethyl, methoxyethyl, etc.), etc. In particular, trifluoromethyl is preferred for the haloalkyl, and methoxymethyl is preferred for the alkoxyalkyl.
[0064] The optionally substituted alkenyl represented by R1 includes, for example, alkenyl having 2 to 8 carbon atoms, preferably 3 to 6 carbon atoms, such as allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, hexadienyl, etc. In particular, allyl is preferred. When the alkenyl is substituted, the substituent is, for example, halogen (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine), alkoxy having 1 to 8, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.), etc.
[0065] The alkynyl represented by R1 includes, for example, alkynyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as propargyl, ethynyl, butynyl, etc. When the alkynyl is substituted, the substituent is, for example, halogen (e.g., fluorine, chlorine, bromine, iodine, preferably fluorine), alkoxy having 1 to 8 carbon atoms, preferably 1 to 4 carbon atoms (e.g., methoxy, ethoxy, propoxy, butoxy, etc.), etc.
[0066] The substituted carbonyl represented by R1 includes, for example, (optionally substituted alkyl)carbonyl, (optionally substituted aryl)carbonyl, (optionally substituted heterocyclic group)carbonyl, etc.
[0067] The substituted sulfonyl represented by R1 includes, for example, (optionally substituted alkyl)sulfonyl, (optionally substituted aryl)sulfonyl, (optionally substituted heterocyclic group)sulfonyl, etc.
[0068] The optionally substituted alkyl, optionally substituted aryl and optionally substituted heterocyclic group in the substituted carbonyl or substituted sulfonyl include those represented by R1 described above.
[0069] The alkyl represented by R2 includes, for example, alkyl having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methyl, ethyl propyl, isopropyl, butyl, isobutyl, t-butyl, etc. In particular, methyl or ethyl is preferred.
[0070] The alkenyl represented by R2 includes, for example, alkenyl having 2 to 8 carbon atoms, preferably 3 to 6 carbon atoms, such as allyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, hexadienyl, etc. In particular, allyl is preferred.
[0071] The alkynyl represented by R2 includes, for example, alkynyl having 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, such as propargyl, ethynyl, butynyl, etc.
[0072] The cycloalkyl represented by R2 includes, for example, cycloalkyl having 3 to 8 carbon atoms, preferably 3 to 6 carbon atoms, such as cyclopropyl, cyclopentyl cyclohexyl, etc.
[0073] R2 is preferably alkyl or alkenyl. In particular, methyl, ethyl and allyl are preferred.
[0074] The optionally substituted heterocyclic group represented by R3 includes unsubstituted or substituted heterocyclic groups. The heterocyclic group is a 5 to 7 membered heterocyclic group containing in the ring 1 to 4 heteroatoms selected from nitrogen, sulfur and oxygen. Examples of the heterocyclic group include isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl), oxazolyl (e.g., oxazol-2-yl, oxazol-5-yl), thiazolyl (e.g., thiazol-2-yl), isothiazolyl (e.g., isothiazol-5-yl), thiadiazolyl [e.g., 1,3,4-thiadiazolyl (e.g., 1,3,4-thiadiazol-2-yl), 1,2,4-thiadiazolyl, etc.], pyrrolyl, pyrazolyl (e.g., pyrazol-1-yl, pyrazol-5-yl), furyl (e.g., 2-furyl), thienyl (e.g., 2-thienyl), imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl), triazolyl [e.g., 1,2,4-triazolyl (e.g., 1H-1,2,4-triazol-1-yl, 4H-1,2,4-triazol-4-yl, 1,2,4-triazol-5-yl), etc.], tetrazolyl (e.g., 1H-tetrazol-5-yl, 2H-tetrazol-5-yl), oxadiazolyl [e.g., 1,3,4-oxadiazolyl (e.g., 1,3,4-oxadiazol-2-yl), 1,2,4-oxadiazolyl (e.g., 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl), etc.], thiazolinyl (e.g., 2-thiazolin-2-yl), isoxazolinyl (e.g., 2-isoxazolin-3-yl), imidazolinyl (e.g., 2-imidazolin-2-yl), oxazolinyl (e.g., 2-oxazolin-2-yl), thiazolidinyl, etc. The heterocyclic group may form a condensed ring with a carbocycle or another heterocycle. At any possible position, the heterocyclic group contains a bond to the oxime carbon atom in the formula (I).
[0075] Examples of the substituent of the substituted heterocyclic group represented by R3 include the above substituents of the substituted heterocyclic group represented by R1. In particular, halogenated lower alkyl or lower alkyl is preferred.
[0076] R3 is preferably imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl, etc.), imidazolinyl (e.g., 2-imidazolin-2-yl, etc.), triazolyl (e.g., 1H-1,2,4-triazol-1-yl, etc.), isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl, etc.), oxazolyl (e.g., oxazol-2-yl, etc.), tetrazolyl (e.g., 1H-tetrazol-5-yl, etc.), oxadiazolyl (e.g., 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, etc.), isoxazolinyl (e.g., 2-isoxazolin-3-yl, 2-isoxazolin-5-yl, etc.), oxazolinyl (e.g., 2-oxazolin-2-yl, etc.), pyrazolyl (e.g., pyrazol-1-yl, pyrazol-5-yl, etc.), thiazolinyl (e.g., 2-thiazolin-2-yl, etc.), furyl (2-furyl, etc.), isothiazolyl (e.g., isothiazol-5-yl, etc.), thiazolidinyl (e.g., thiazolidin-2-yl, etc.), etc., each of which is unsubstituted or substituted.
[0077] R3 is more preferably imidazolyl (e.g., imidazol-1-yl, imidazol-2-yl, etc.); imidazolyl substituted with lower alkyl (preferably methyl) (e.g., l-methylimidazol-2-yl, 2-methylimidazol-1-yl, 4-methylimidazol-1-yl, 5-methylimidazol-1-yl, etc.); imidazolinyl (e.g., 2-imidazolin-2-yl, etc.); triazolyl (e.g., 1H-1,2,4-triazol-1-yl, etc.); imidazolinyl substituted with lower alkyl (preferably methyl) (e.g., 1-methyl-2-imidazolin-2-yl, etc.); isoxazolyl (e.g., isoxazol-3-yl, isoxazol-5-yl, etc.); isoxazolyl substituted with lower alkyl (preferably methyl) (e.g., 3-methylisoxazol-5-yl, 5-methylisoxazol-3-yl, etc.); oxadiazolyl (e.g., 1,2,4-oxadiazol-3-yl, 1,3,4-oxadiazol-2-yl, etc.); oxadiazolyl substituted with lower alkyl (preferably methyl or ethyl) (e.g., 5-methyl-1,2,4-oxadiazol-3-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, etc.); isoxazolinyl (e.g., 2-isoxazolin-3-yl, etc.); isoxazolinyl substituted with lower alkyl (preferably methyl) (e.g., 3-methyl-2-isoxazolin-5-yl, etc.); oxazolinyl (e.g., 2-oxazolin-2-yl, etc.); pyrazolyl (e.g., pyrazol-1-yl, etc.); pyrazolyl substituted with lower alkyl (preferably methyl) (e.g., 1-methylpyrazol-5-yl, etc.); thiazolinyl (e.g., 2-thiazolin-2-yl, etc.); furyl (e.g., 2-furyl, etc.); tetrazolyl substituted with lower alkyl (preferably methyl) (e.g., 2-methyltetrazol-5-yl, etc.); isothiazolyl substituted with lower alkyl (preferably methyl) (e.g., 3-methylisothiazol-5-yl, etc.); thiazolidinyl (e.g., thiazolidin-2-yl, etc.); thiazolidinyl substituted with lower alkyl (e.g., 3-methylthizolidin-2-yl, etc.), etc.
[0078] The alkyl represented by R4 includes the above alkyl represented by R2.
[0079] The alkoxy represented by R4 includes, for example, alkoxy having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, s-butoxy, t-butoxy, etc.
[0080] The halogen represented by R4 includes, for example, fluorine, chlorine, bromine, and iodine.
[0081] The halogenated alkyl represented by R4 includes the above alkyl represented by R2 which is substituted with at least one halogen (e.g., fluorine, chlorine, bromine, iodine), such as trifluoromethyl, etc.
[0082] R4 is preferably hydrogen.
[0083] The alkyl and acyl represented by R16 include the above alkyl and acyl represented by R9 or R10, respectively.
[0084] M is preferably an oxygen atom, sulfur atom or NR16, more preferably an oxygen atom.
[0085] When R3 is imidazol-1-yl or 1,2,4-triazol-1-yl, n is 1.
[0086] The compound of the present invention has two kinds of isomers: E and Z isomers. The present invention includes these isomers and mixtures of the isomers in any mixing ratios. This is herein indicated by the wave line (˜) in the formulas.
[0087] In addition, the compound of the present invention includes its hydrochloric acid salt, sulfuric acid salt, nitric acid salt, oxalic acid salt and p-toluenesulfonic acid salt.
[0088] Specific examples of the compound of the formula (I) of the present invention include compounds described in Examples hereinafter. Particularly preferred are the compounds of the formula (I) wherein
[0089] R1 is phenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 1: Compound Nos. correspond to those in Examples hereinafter);
[0090] R1 is 4-chlorophenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 7);
[0091] R1 is 2-methylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 13);
[0092] R1 is 4-methylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 15);
[0093] R1 is 2-ethylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 16);
[0094] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 39);
[0095] R1 is phenyl, R2 is ethyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 61);
[0096] R1 is phenyl, R2 is allyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 81);
[0097] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 1-methylimidazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 136);
[0098] R1 is 4-chloro-2-methylphenyl, R2 is methyl, R3 is 1-methylimidazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 141);
[0099] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 336);
[0100] R1 is 5-trifluoromethylpyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 387);
[0101] R1 is 5-trifluoromethyl-3-chloropyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 390);
[0102] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 5-methylisoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 436);
[0103] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 3-methylisoxazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 636);
[0104] R1 is 5-trifluoromethyl-3-chloropyridin-2-yl, R2 is methyl, R3 is 3-methylisoxazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 690);
[0105] R1 is 2-methylphenyl, R2 is methyl, R3 is 1,3,4-oxadiazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 712);
[0106] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 1,3,4-oxadiazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 736);
[0107] R1 is 4-chloro-2-methylphenyl, R2 is methyl, R3 is 1,3,4-oxadiazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 741);
[0108] R1 is 4-chlorophenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 807);
[0109] R1 is 2-methylphenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 812);
[0110] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 836);
[0111] R1 is 2-methylphenyl, R2 is methyl, R3 is 5-methyl-1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 912);
[0112] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 5-methyl-1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 936);
[0113] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 1-methyl-2-imidazolin-2-yl, R4 is hydrogen, and n is 1 (Compound No. 1136);
[0114] R1 is 4-chlorophenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 1584);
[0115] R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 2-methyl-2H-tetrazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 2036);
[0116] R1 is 3,5-dichloropyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2276);
[0117] R1 is 5-chloro-3-trifluoromethylpyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2306);
[0118] R1 is a group represented by the formula (a), R9 is 4-chlorophenyl, R10 is methyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2387);
[0119] R1 is a group of by the formula (a), R9 is 3-trifluoromethylphenyl, R10 is methyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2399);
[0120] R1 is a group of the formula (a), R9 is 3,4-dichlorophenyl, R10 is methyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2408);
[0121] R1 is a group represented by the formula (a), R9 is 4-chlorophenyl, R10 is methyl, R2 is methyl, R3 is 3-methylisoxazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 2507);
[0122] R1 is a group of the formula (a), R9 is 3-trifluoromethylphenyl, R10 is methyl, R2 is methyl, R3 is thiazolidin-2-yl, R4 is hydrogen, and n is 1 (Compound No. 2799); or
[0123] R1 is a group of the formula (a), R9 is 3-trifluoromethylphenyl, R10 is methyl, R2 is methyl, R3 is 3-methylthiazolidin-2-yl, R4 is hydrogen, and n is 1 (Compound No. 2839).
[0124] The compound (I) (i.e., the compound of the formula (I); hereinafter the compounds of other formulas are sometimes abbreviated likewise) can be prepared, for example, according to the following synthetic routes.
[0125] [Route 1]
9
[0126] wherein A is halogen (e.g., chlorine, bromine, iodine, etc.), and the other symbols are as defined above.
[0127] The compound of the formula (IV) can be prepared by reacting the compound (IIa) with the compound (III) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0128] In this reaction, the amount of the compound (III) to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (IIa).
[0129] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.
[0130] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran (THF), dioxane, etc.), water, mixtures thereof, etc.
[0131] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 48 hours.
[0132] The compound (IV) thus obtained can be used in the next step as the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0133] The acid halide (Iha) used as the starting material in this reaction can be prepared according to JP-A 5-331124, for example, by halogenating the corresponding carboxylic acid with a thionyl halide (e.g., thionyl chloride, etc.), phosphoryl halide (e.g., phosphoryl chloride, etc.), phosgene, etc.
[0134] [Route 1 (continued)]
10
[0135] wherein each symbol is as defined above.
[0136] The compound of the formula (V) can be prepared by reacting the above compound (IV) with a halogenating agent in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0137] Examples of the halogenating agent to be used include thionyl halides (e.g., thionyl chloride, thionyl bromide, etc.), phosphoryl halides (e.g., phosphoryl chloride, phosphoryl bromide, etc.), phosphorus halides (e.g., phosphorus pentachloride, phosphorus trichloride, phosphorus pentabromide, phosphorus tribromide, etc.), phosgene, oxalyl halides (e.g., oxalyl chloride, etc.), triphenylphosphine/carbon tetrachloride, triphenylphosphine/carbon tetrabromide, etc. The amount of the halogenating agent to be used is 1 equivalent or more, preferably 1 to 4 equivalents.
[0138] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), nitrites (e.g., acetonitrile, etc.), mixed solvents thereof, etc.
[0139] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 120° C. The reaction time varies with the kind of compound, and is 0.1 to 48 hours.
[0140] The compound (V) thus obtained can be used in the next step as the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0141] [Route 1 (continued)]
11
[0142] wherein each symbol is as defined above.
[0143] The compound of the formula (VII) can be prepared by reacting the compound (VI) with the compound (III) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0144] The amount of the compound (III) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (VI).
[0145] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.
[0146] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), water, mixed solvents thereof, etc.
[0147] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 48 hours.
[0148] The compound (VII) thus obtained can be used in the next step as the reaction mixture or the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0149] The compound (VI) used as the starting material in this reaction can be prepared according to Takahashi et al. Tetrahedron Letters 22 (28), 2651-2654 (1981), for example, by halogenating the corresponding phthalide with triphenylphosphine dichloride, etc.
[0150] [Route 1 (continued)]
12
[0151] wherein each symbol is as defined above.
[0152] The compound of the formula (VIII) can be prepared by reacting the compound (VII) with a halogenating agent in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0153] Examples of the halogenating agent to be used include thionyl halides (e.g., thionyl chloride, thionyl bromide, etc.), phosphoryl halides (e.g., phosphoryl chloride, phosphoryl bromide, etc.), phosphorus halides (e.g., phosphorus pentachloride, phosphorus trichloride, etc.), phosgene, and oxalyl halides (e.g., oxalyl chloride, etc.). The amount of the halogenating agent to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0154] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), mixed solvents thereof, etc.
[0155] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 120° C. The reaction time varies with the kind of compound, and is 0.1 to 48 hours.
[0156] The compound (VIII) thus obtained can be used in the next step as the crude product or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0157] [Route 1 (continued)]
13
[0158] wherein each symbol is as defined above.
[0159] The compound of the formula (Va) can be prepared by reacting the compound (VIII) with the compound (IX) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0160] The amount of the compound (IX) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (VIII).
[0161] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.
[0162] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0163] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0164] The compound (Va) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0165] [Route 1 (continued)]
14
[0166] wherein each symbol is as defined above, and, in this reaction, R3 is preferably pyrrolyl (e.g., pyrrol-1-yl, etc.), imidazolyl (e.g., imidazol-1-yl, etc.), pyrazolyl (e.g., pyrazol-1-yl, etc.) or triazolyl (e.g., 1H-1,2,4-triazol-1-yl, etc.).
[0167] The compound of the formula (I) of the present invention can be prepared by reacting the compound (V) with the compound (X) in the presence or absence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0168] The amount of the compound (X) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (V).
[0169] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal hydrides (e.g., sodium hydride, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 5 equivalents.
[0170] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethate, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0171] The reaction temperature is −30° C. to 170° C., preferably −10° C. to 140° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0172] If necessary, the desired compound (I) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0173] [Route 2]
15
[0174] wherein Z is lithium or magnesium halide (e.g., −MgBr, −MgI, etc.), L is halogen (e.g., chlorine, bromine, iodine, etc.), alkoxy (e.g., lower alkoxy such as methoxy, ethoxy, propoxy, etc.), imidazol-1-yl or N-methyl-N-methoxyamino, R3 is an optionally substituted heterocyclic group, and the other symbols are as defined above.
[0175] The compound of the formula (XIV) can be prepared by reacting the compound (XI) with the compound (XII) or (XIII) in an appropriate solvent (alone or as a mixture).
[0176] The amount of the compound (XII) or (XIII) to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XI).
[0177] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), triethylamine, mixed solvents thereof, etc.
[0178] The reaction temperature is −100° C. to 100° C., preferably −80° C. to 40° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0179] The compound (XIV) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0180] The compound (XI) used as the starting material in this reaction can be prepared according to JP-A 3-246268 or JP-A 5-97768, for example, by reacting a compound corresponding to the compound (XI) wherein the moiety Z is halogen with butyl lithium or magnesium.
[0181] [Route 2 (continued)]
16
[0182] wherein each symbol is as defined above.
[0183] The compound of the formula (XIV) can be prepared by reacting the compound (II) with the compound (XV) in an appropriate solvent (alone or as a mixture).
[0184] The amount of the compound (XV) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (II).
[0185] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), triethylamine, mixed solvents thereof, etc.
[0186] The reaction temperature is −100° C. to 100° C., preferably −80° C. to 40° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0187] The compound (XIV) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0188] The compound (XV) can be prepared by reference to A. R. Katritzky, Handbook of Heterocyclic Chemistry, 360-361 (1985), for example, by lithiating the corresponding heterocyclic compound with butyl lithium, etc., or by reacting the corresponding halogenated heterocyclic compound with magnesium.
[0189] [Route 2 (continued)]
17
[0190] wherein each symbol is as defined above.
[0191] The compound of the formula (I) of the present invention can be prepared by reacting the compound (XIV) with the compound (III) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in an appropriate solvent (alone or as a mixture).
[0192] The amount of the compound (III) to be used in this reaction is 1 equivalent or more, preferably 1 to 4 equivalents, based on the compound (XIV).
[0193] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.
[0194] The reaction temperature is 0° C. to 160° C., preferably 60° C. to 130° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0195] If necessary, the desired compound (I) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0196] [Route 2 (continued)]
18
[0197] wherein each symbol is as defined above.
[0198] The compound of the formula (XVI) can be prepared by reacting the compound (XIV) with hydroxylamine or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in an appropriate solvent (alone or as a mixture).
[0199] The amount of the hydroxylamine or a salt thereof to be used in this reaction is 1 equivalent or more, preferably 1 to 4 equivalents, based on the compound (XIV).
[0200] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.
[0201] The reaction temperature is 0° C. to 160° C., preferably 60° C. to 130° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0202] The compound (XVI) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0203] [Route 2 (continued)]
19
[0204] wherein Y is halogen (e.g., chlorine, bromine, iodine, etc.), alkylsulfonyloxy (e.g., lower alkylsulfonyloxy such as methylsulfonyloxy, ethylsulfonyloxy, etc.) or alkoxysulfonyloxy (e.g., lower alkoxysulfonyloxy such as methoxysulfonyloxy, ethoxysulfonyloxy, etc.), and the other symbols are as defined above.
[0205] The compound of the formula (I) of the present invention can be prepared by reacting the compound (XVI) with the compound (XVII) in the presence of a base in an appropriate solvent (alone or as a mixture).
[0206] The amount of the compound (XVII) to be used in this reaction is 1 equivalent, preferably 1 to 2 equivalents, based on the compound (XVI).
[0207] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0208] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0209] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0210] If necessary, the desired compound (I) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0211] [Route 3]
20
[0212] wherein R5 is hydrogen or alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.), and the other symbols are as defined above.
[0213] The compound of the formula (XX) can be prepared by reacting the compound (XVIII) with the compound (XIX) in the absence of a solvent or in an appropriate solvent (alone or as a mixture), for example, by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).
[0214] The amount of the compound (XIX) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XVIII).
[0215] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), mixed solvents thereof, etc.
[0216] The reaction temperature is 0° C. to 180° C., preferably 20° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0217] The compound (XX) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0218] The compound (XVIII) used as the starting material in this reaction can be prepared, for example, according to JP-A 3-246268 or JP-A 5-97768, for example, by reacting the corresponding carboxylic acid ester with ammonia or by subjecting the corresponding α-ketoamide to oximation.
[0219] [Route 3 (continued)]
21
[0220] wherein R6 is hydrogen or alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.), and the other symbols are as defined above.
[0221] The compound of the formula (Ia) of the present invention can be prepared by reacting the compound (XX) with the compound (XXI) in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).
[0222] The amount of the compound (XXI) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XX).
[0223] Examples of the acid to be used include aliphatic carboxylic acids (e.g., acetic acid, etc.). The amount of the acid to be used is 1 equivalent or more, preferably 5 to 50 equivalents, based on the compound (XX).
[0224] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.
[0225] The reaction temperature is 0° C. to 180° C., preferably 20° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0226] If necessary, the desired compound (Ia) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0227] [Route 4]
22
[0228] wherein each symbol is as defined above.
[0229] The compound of the formula (XXII) can be prepared by reacting the compound (XX) with hydroxylamine in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).
[0230] The amount of the hydroxylamine to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XX).
[0231] Examples of the acid to be used include aliphatic carboxylic acids (e.g., acetic acid, etc.). The amount of the acid to be used is 1 equivalent or more, preferably 5 to 50 equivalents, based on the compound (XX).
[0232] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), water, mixed solvents thereof, etc.
[0233] The reaction temperature is −10° C. to 120° C., preferably 0° C. to 80° C. The reaction time varies with the kind of compound, and is 0.1 to 40 hours.
[0234] The compound (XXII) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0235] [Route 4 (continued)]
23
[0236] wherein each symbol is as defined above.
[0237] The compound of the formula (Ib) of the present invention can be prepared by subjecting the compound (XXII) to ring closure reaction in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Y. Lin et al., J. Org. Chem., 44, 4160 (1979).
[0238] Examples of the acid to be used include aliphatic carboxylic acids (e.g., acetic acid, etc.). The amount of the acid to be used is 1 equivalent or more, preferably 5 to 50 equivalents, based on the compound (XXII).
[0239] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.
[0240] The reaction temperature is 20° C. to 180° C., preferably 50° C. to 140° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0241] If necessary, the desired compound (Ib) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0242] [Route 5]
24
[0243] wherein each symbol is as defined above.
[0244] The compound of the formula (Ib) of the present invention can be prepared by reacting the compound (XXIII) with the compound (XXIV) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to S. Chiou et al., J. Heterocyclic Chem., 26, 125 (1989).
[0245] The amount of the compound (XXIV) to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XXIII).
[0246] Examples of the base to be used include amines (e.g., pyridine, triethylamine, etc.). The amount of the base to be used is 1 equivalent or more, preferably 3 to 20 equivalents, based on the compound (XXIII).
[0247] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.
[0248] The reaction temperature is 20° C. to 180° C., preferably 50° C. to 140° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0249] If necessary, the desired compound (Ib) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0250] The compound (XXIII) used as the starting material in this reaction can be prepared, for example, according to Japanese Patent Application No. 5-56143, for example, by subjecting the corresponding α-methoxyimino(substituted)-benzyl cyanide to hydrolysis with a base (e.g., sodium hydroxide, potassium hydroxide, etc.) to give a carboxylic acid, and then halogenating the carboxylic acid with a thionyl halide (e.g., thionyl chloride, etc.), phosphoryl halide (e.g., phosphoryl chloride, etc.), etc.
[0251] [Route 6]
25
[0252] wherein R7 is alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.), and the other symbols are as defined above.
[0253] The compound of the formula (XXVI) can be prepared by reacting the compound (XXV) with a monohydrate of the compound (XXIa) or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in an appropriate solvent (alone or as a mixture).
[0254] The amount of the compound (XXIa) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XXV).
[0255] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), ethers (e.g., THF, dioxane, etc.), water, mixed solvents thereof, etc.
[0256] The reaction temperature is 0° C. to 160° C., preferably 10° C. to 130° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0257] The compound (XXVI) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0258] The compound (XXV) used as the starting material in this reaction can be prepared, for example, according to JP-A 4-295454, for example, by subjecting the corresponding α-ketocarboxylic acid ester or a ketal at the α-position of the ester to oximation.
[0259] [Route 6 (continued)]
26
[0260] wherein each symbol is as defined above.
[0261] The compound of the formula (Ic) of the present invention can be prepared by reacting the compound (XXVI) with the compound (XXVII) in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to C. Ainaworth, J. Am. Chem. Soc., 77, 1148 (1955).
[0262] The amount of the compound (XXVII) to be used in this reaction is 1 equivalent or more, preferably 1 to 20 equivalents, based on the compound (XXVI).
[0263] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.
[0264] The reaction temperature is 20° C. to 200° C., preferably 50° C. to 170° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0265] If necessary, the desired compound (Ic) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0266] [Route 7]
27
[0267] wherein each symbol is as defined above.
[0268] The compound of the formula (XXIX) can be prepared by reacting the compound (XXVIII) with hydroxylamine or a salt thereof (e.g., hydrochloric acid salt, sulfuric acid salt) in the presence or absence of a base in an appropriate solvent (alone or as a mixture).
[0269] The amount of the hydroxylamine or a salt thereof to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XXVIII).
[0270] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, etc.), amines (e.g., pyridine, triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0271] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.
[0272] The reaction temperature is 0° C. to 160° C., preferably 20° C. to 110° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0273] The compound (XXIX) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0274] The compound (XXVIII) used as the starting material in this reaction can be prepared, for example, according to Route 13, 14 or 15, or Japanese Patent Application No. 4-324120, for example, by introducing the cyano moiety to the corresponding (substituted)benzyl halide using an alkaline metal cyanide (e.g., sodium cyanide, etc.), and then subjecting the resulting compound to oximation.
[0275] [Route 7 (continued)]
28
[0276] wherein each symbol is as defined above except that R5 of the compound (XXX) is other than hydrogen and preferably lower alkyl such as methyl, ethyl, propyl, etc.
[0277] The compound of the formula (Id) of the present invention can be prepared by reacting the compound (XXIX) with the compound (XXVII) or (XXX) in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to U.S. Pat. No. 3,910,942.
[0278] The amount of the compound (XXVII) or (XXX) to be used in this reaction is 1 equivalent or more, preferably 1 to 20 equivalents, based on the compound (XXIX).
[0279] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.
[0280] The reaction temperature is 40° C. to 200° C., preferably 60° C. to 180° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0281] If necessary, the desired compound (Id) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0282] The compounds of the formulas (Ie), (If) and (Ig) of the present invention can be prepared according to the following Route 8.
[0283] [Route 8]
29
[0284] wherein each symbol is as defined above.
[0285] The compound of the formula (Ie) of the present invention can be prepared by reacting the compound (XXVIII) with an azide compound in the presence of ammonium chloride in an appropriate solvent (alone or as a mixture) by reference to K. Kubo, J. Med. Chem., 36, 2182 (1993).
[0286] Examples of the azide compound to be used include alkaline metal azides (e.g., sodium azide, potassium azide, etc.), etc. The amount of the azide compound to be used is 1 equivalent or more, preferably 1 to 15 equivalents, based on the compound (XXVIII). The amount of the ammonium chloride to be used is 1 equivalent or more, preferably 1 to 15 equivalents, based on the compound (XXVIII).
[0287] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), ethers (e.g., dioxane, etc.), mixed solvents thereof, etc.
[0288] The reaction temperature is 40° C. to 200° C., preferably 60° C. to 180° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0289] The desired compound (le) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0290] [Route 8 (continued)]
30
[0291] wherein each symbol is as defined above.
[0292] The compound of the formula (If) or (Ig) of the present invention can be prepared by reacting the compound (Ie) with the compound (XXXI) in the presence of a base in an appropriate solvent (alone or as a mixture).
[0293] The amount of the compound (XXXI) be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (Ie).
[0294] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 3 equivalents.
[0295] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0296] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with-the kind of compound, and is 0.5 to 90 hours.
[0297] If necessary, the desired compound (If) and (Ig) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0298] The compounds of the formulas (Ih) and (Ii) of the present invention can be prepared according to the following Route 9.
[0299] [Route 9]
31
[0300] wherein each symbol is as defined above.
[0301] The compound of the formula (XXXII) can be prepared by reacting the compound (XXVIII) with methanol in the presence of an acid by reference to, for example, JP-A 5-271223.
[0302] The amount of the methanol to be used in this reaction is 1 equivalent or more, preferably 1 to 1.2 equivalents, based on the compound (XXVIII).
[0303] Examples of the acid to be used include hydrochloric acid, hydrobromic acid, etc. The amount of the acid to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXVIII).
[0304] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, ethyl ether, etc.), mixed solvents thereof, etc.
[0305] The reaction temperature is −30° C. to 150° C., preferably 0° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0306] The compound (XXXII) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0307] [Route 9 (continued)]
32
[0308] wherein each symbol is as defined above.
[0309] The compound of the formula (XXXIV) can be prepared by reacting the compound (XXXII) or a salt thereof (e.g., hydrochloric acid, hydrobromic acid, etc.) with the compound (XXXIII) by reference to, for example, JP-A 5-271223.
[0310] The amount of the compound (XXXIII) to be used in this reaction is 1 equivalent or more, preferably 1 to 1.2 equivalents, based on the compound (XXXII).
[0311] Examples of the solvent to be used include alcohols (e.g., methanol, ethanol, propanol, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.
[0312] The reaction temperature is −30° C. to 150° C., preferably 0° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0313] The compound (XXXIV) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0314] [Route 9 (continued)]
33
[0315] wherein each symbol is as defined above.
[0316] The compound of the formula (Ih) of the present invention can be prepared by subjecting the compound (XXXIV) or a salt thereof (e.g., hydrochloric acid, hydrobromic acid, etc.) to ring closure reaction in the presence of an acid in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to, for example, JP-A 5-271223.
[0317] Examples of the acid to be used include hydrochloric acids, hydrobromic acid, etc. The amount of the acid to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXIV).
[0318] Examples of the solvent to be used include alcohols (e.g., methanol, ethanol, propanol, etc.), ethers (e.g., THF, dioxane, etc.), mixed solvents thereof, etc.
[0319] The reaction temperature is 10° C. to 150° C., preferably 30° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0320] If necessary, the desired compound (Ih) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0321] [Route 9 (continued)]
34
[0322] wherein each symbol is as defined above.
[0323] The compound of the formula (Ii) of the present invention can be prepared by reacting the compound (Ih) with the compound (XXXI) in the presence of a base in an appropriate solvent (alone or as a mixture).
[0324] The amount of the compound (XXXI) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (Ih).
[0325] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0326] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0327] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0328] If necessary, the desired compound (Ii) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0329] The compound of the formula (Ij) of the present invention can be prepared according to the following Route 10.
[0330] [Route 10]
35
[0331] wherein W is oxygen, sulfur or N—R5, and R5 and the other symbols are as defined above.
[0332] The compound of the formula (Ij) of the present invention can be prepared by reacting the compound (XXVIII) with the compound (XXXV) or a salt thereof (e.g., hydrochloric acid salt, hydrobromic acid salt, etc.) in the presence or absence of a base in the presence or absence of a metal salt in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to Doris P. Schumacher et al., J. Org. Chem., 55, 5291 (1990).
[0333] The amount of the compound (XXXV) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XXVIII).
[0334] Examples of the base to be used include amines (e.g., triethylamine, etc.). The amount of the base to be used is 1 equivalent or more, preferably 1 to 6 equivalents, based on the compound (XXVIII).
[0335] Examples of the metal salt to be used include potassium carbonate, zinc acetate, etc. The amount of the metal salt to be used is 0.01 to 0.5 equivalent, preferably 0.02 to 0.2 equivalent, based on the compound (XXVIII).
[0336] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), alcohols (e.g., butanol, 2-methoxyethanol, ethylene glycol, glycerol, etc.), mixed solvents thereof, etc.
[0337] The reaction temperature is 20° C. to 200° C., preferably 50° C. to 160° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0338] If necessary, the desired compound (Ij) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0339] The compound of the formula (Ik) of the present invention can be prepared according to the following Route 11.
[0340] [Route 11]
36
[0341] wherein each symbol is as defined above.
[0342] The compound of the formula (XXXVI) can be prepared by reacting the compound (XXVIII) or the compound (XXV) with a reducing agent in an appropriate solvent (alone or as a mixture) by reference to, for example, L.-F Tietze and Th. Eicher, “Reaktionen und Synthesen im organisch-chemischen Praktikum”, pp. 84-97 (1981).
[0343] Examples of the reducing agent to be used include alkylaluminum hydrides (e.g., diisobutylaluminum hydride, etc.). The amount of the reducing agent to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0344] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, ethyl ether, etc.), mixed solvents thereof, etc.
[0345] The reaction temperature is −100° C. to 80° C., preferably −70° C. to 30° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0346] The compound (XXXVI) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0347] [Route 11 (continued)]
37
[0348] wherein each symbol is as defined above.
[0349] The compound of the formula (Ik) of the present invention can be prepared by reacting the compound (XXXVI) with the compound (XXXVII) in the presence of a base in an appropriate solvent (alone or as a mixture) according to, for example, JP-A 58-131984.
[0350] The amount of the compound (XXXVII) to be used in this reaction is I equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXVI).
[0351] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0352] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), alcohols (e.g., methanol, ethanol, propanol, etc.), mixed solvents thereof, etc.
[0353] The reaction temperature is 30° C. to 150° C., preferably 50° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0354] If necessary, the desired compound (Ik) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0355] The compound of the formula (In) of the present invention can be prepared according to the following Route 12.
[0356] [Route 12]
38
[0357] wherein R8 is hydrogen, alkyl (e.g., lower alkyl such as methyl, ethyl, propyl, etc.) or halogen (e.g., fluorine, chlorine, bromine, iodine), and the other symbols are as defined above.
[0358] The compound of the formula (XXXIXa) can be prepared by reacting the compound (XXXVIII) with a Lewis acid in an appropriate solvent (alone or a mixture).
[0359] The compound (XXXVIII) is synthesized by a modified method of Routes 1 to 11.
[0360] Examples of the Lewis acid to be used include aluminium chloride, aluminium bromide, boron trifluoride, boron trichloride, ferric chloride, etc.
[0361] The amount of the Lewis acid to be used is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XXXVIII).
[0362] Examples of the solvent to be used include anisole, nitromethane, nitroethane, mixed solvents thereof, etc.
[0363] The reaction temperature is −30° C. to 120° C., preferably −10° C. to 80° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0364] Alternatively, the compound (XXXIXa) can be prepared by reacting the compound (XXXVIII) with hydrogen in the presence of a catalyst in an appropriate solvent (alone or as a mixture).
[0365] The amount of the hydrogen to be used is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXVIII).
[0366] Examples of the catalyst to be used include palladium-carbon, etc. The amount of the catalyst to be used is 0.01 equivalent or more, preferably 0.01 to 0.2 equivalent, based on the compound (XXXVIII).
[0367] Examples of the solvent to be used include ethyl acetate, alcohols (e.g., methanol, ethanol, propanol, etc.), water, mixed solvents thereof, etc.
[0368] The reaction temperature is −30° C. to 120° C., preferably −10° C. to 80° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0369] The compound (XXXIXa) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0370] [Route 12 (continued)]
39
[0371] wherein each symbol is as defined above.
[0372] The compound of the formula (In) of the present invention can be prepared by reacting the compound (XXXIX) with the compound (XL) in the presence of a base in an appropriate solvent (alone or as a mixture).
[0373] The amount of the compound (XL) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XXXIX).
[0374] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0375] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.); halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0376] The reaction temperature is 0° C. to 190° C., preferably 10° C. to 160° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0377] If necessary, the desired compound (In) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0378] The compound (XXVIII) which can be used as the starting material in the above Schemes 19, 21, 23, 27 and 28 can be prepared according to the following Route 13, 14 or 15.
[0379] [Route 13]
40
[0380] wherein each symbol is as defined above.
[0381] The compound of the formula (XXVIII) can be prepared by reacting the compound (V) with an alkaline metal cyanide (e.g., sodium cyanide, potassium cyanide, etc.) in an appropriate solvent (alone or as a mixture).
[0382] The amount of the alkaline metal cyanide to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (V).
[0383] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0384] The reaction temperature is 0° C. to 190° C., preferably 20° C. to 160° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0385] The compound (XXVIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.
[0386] [Route 14]
41
[0387] wherein each symbol is as defined above.
[0388] The compound of the formula (XXVIII) can be prepared by reacting the compound (XVIII) with an acid anhydride in the presence or absence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to, for example, J. Goto et al., J. Antibiotics, 37, 557 (1984).
[0389] Examples of the acid anhydride to be used include acetic anhydride, trifluoroacetic anhydride, etc. The amount of the acid anhydride to be used is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XVIII).
[0390] Examples of the base to be used include amines (e.g., pyridine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 30 equivalents, based on the compound (XVIII). Examples of the solvent to be used is aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g. cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), mixed solvents thereof, etc.
[0391] The reaction temperature is −30° C. to 160° C., preferably −10° C. to 110° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0392] The compound (XXVIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0393] [Route 15]
42
[0394] wherein R4 is as defined above.
[0395] The compound of the formula (XLII) can be prepared by reacting the compound (XLI) with an alkyl nitrite in the presence of a base in an appropriate solvent (alone or as a mixture) in the presence or absence of a phase-transfer catalyst.
[0396] Examples of the alkyl nitrite to be used include methyl nitrite, ethyl nitrite, propyl nitrite, isopropyl nitrite, butyl nitrite, isoamyl nitrite, etc. The amount of the alkyl nitrite to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0397] Examples of the phase-transfer catalyst to be used include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium hydrogensulfate, tetramethylammonium bromide, benzyltriethylammonium chloride, tris(3,6-dioxaheptyl)amine, etc. The amount of the phase-transfer catalyst to be used is 0.005 to 0.5 equivalent, preferably 0.01 to 0.2 equivalent.
[0398] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0399] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), alcohols (e.g., methanol, butanol, etc.), water, mixed solvents thereof, etc.
[0400] The reaction temperature is −10° C. to 120° C., preferably 0° C. to 80° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0401] The compound (XLII) or a salt thereof (e.g., sodium salt, potassium salt, etc.) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0402] The compound (XLI) used as the starting material in this reaction is commercially available from Aldrich.
[0403] [Route 15 (continued)]
43
[0404] wherein each symbol is as defined above.
[0405] The compound of the formula (XLIII) can be prepared by reacting the compound (XLII) or a salt thereof (e.g., sodium salt, potassium salt, etc.) with the compound (XVII) in the presence or absence of a base in the presence or absence of a phase-transfer catalyst in an appropriate solvent (alone or as a mixture).
[0406] The amount of the compound (XVII) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XLII).
[0407] Examples of the phase-transfer catalyst to be used include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium hydrogensulfate, tetramethylammonium bromide, benzyltriethylammonium chloride, tris(3,6-dioxaheptyl)amine, etc. The amount of the phase-transfer catalyst to be used is 0.005 to 0.5 equivalent, preferably 0.01 to 0.2 equivalent.
[0408] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0409] Examples of the solvent to be used is N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0410] The reaction temperature is −20° C. to 140° C., preferably 10° C. to 120° C. The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0411] The compound (XLIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0412] [Route 15 (continued)]
44
[0413] wherein each symbol is as defined above.
[0414] The compound of the formula (XLIV) can be prepared by reacting the compound (XLIII) with a halogenating agent in the presence of a reaction initiator in an appropriate solvent (alone or as a mixture).
[0415] Examples of the halogenating agent to be used include halogenated succinimide (e.g., N-chlorosuccinimide, N-bromosuccinimide, etc.), chlorine, and bromine. The amount of the halogenating agent to be used is 1 equivalent or more, preferably 1 to 1.5 equivalent.
[0416] Examples of the reaction initiator to be used include peroxides (e.g., benzoyl peroxide, etc.), azobisisobutyronitrile, etc. The amount of the reaction initiator to be used is 0.01 equivalent or more, preferably 0.03 to 0.3 equivalent.
[0417] Examples of the solvent to be used include aromatic hydrocarbons (e.g., benzene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., carbon tetrachloride, 1,2-dichloroethane, etc.), mixed solvents thereof, etc.
[0418] The reaction temperature is 20° C. to 160° C., preferably 50° C. to 120° C. The reaction time varies with the kind of compound, and is 0.1 to 48 hours.
[0419] The compound (XLIV) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0420] [Route 15 (continued)]
45
[0421] wherein each symbol is as defined above.
[0422] The compound of the formula (XXVIIIa) can be prepared by reacting the compound (XLIV) with the compound (IX) in the presence of a base in the presence or absence of a phase-transfer catalyst in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0423] The amount of the compound (IX) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (XLIV).
[0424] Examples of the phase-transfer catalyst to be used include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium hydrogensulfate, tetramethylammonium bromide, benzyltriethylammonium chloride, tris(3,6-dioxaheptyl)amine, etc. The amount of the phase-transfer catalyst to be used is 0.005 to 0.5 equivalent, preferably 0.01 to 0.2 equivalent.
[0425] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0426] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0427] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0428] The compound (XXVIIIa) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0429] The compound (XXXIX) which can be used as the starting material in Scheme 31 described above can also be prepared according to the following Route 16.
[0430] [Route 16]
46
[0431] wherein P is a protective group of a hydroxyl group, and the other symbols are as defined above.
[0432] The compound (XLVI) can be prepared by protecting the hydroxyl group of the commercially available compound (XLV) with an appropriate protective group.
[0433] The hydroxyl group can be protected with a group represented by P by a conventional method for protecting a hydroxyl group described in, for example, T. W. Green, “Protective Groups in Organic Synthesis”, p. 1-113, John Willy & Sons (1981); C. B. Reese, “Protective Groups in Organic Chemistry”, J. F. McOmie (ed.), p.95-143, Plenum Press (1973), etc.
[0434] For example, the compounds (XLVI) protected with tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydrothiofuranyl, 1-ethoxyethyl and 1-methyl-1-methoxyethyl can be prepared by reacting the compound (XLV) with the corresponding olefins in the presence of an acid catalyst in an appropriate solvent or in the absence of a solvent.
[0435] The corresponding olefins are 3,4-dihydro-2H-pyran, 2,3-dihydro-4H-thiin, dihydrofuran, dihydrothiofuran, ethyl vinyl ether, and 2-methoxypropene, respectively, and they are commercially available or can be prepared by known methods.
[0436] The amount of the olefin to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the compound (XLV).
[0437] Examples of the acid catalyst include hydrogen chloride, phosphorus oxychloride, p-toluenesulfonic acid, p-toluenesulfonic acid pyridine salt, montmorillonite, bistrimethyl sulfate, acetic acid, p-toluenesulfonic acid polyvinyl pyridinium, trifluoroacetic acid, boron trifluoride etherate (BF3·OEt2) and acidic ion-exchange resins, etc.
[0438] When a solvent is used, non-alcoholic solvents can be used. Examples of the solvent include hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), ethers (e.g., diethyl ether, tetrahydrofuran, dioxane, etc.), esters (e.g., ethyl acetate, etc.), N,N-dimethylformamide, mixed solvents thereof, etc.
[0439] The reaction temperature is −30° C. to 100° C., preferably 0° C. to 60° C. The reaction time is normally 15 minutes to 24 hours.
[0440] The compound (XLVI) protected with a silyl enol type protective group can be obtained by reacting the compound (XLV) with an appropriate silylating agent. In general, it can be obtained by reacting the compound (XLV) with chlorosilane in the presence of a base in an appropriate solvent.
[0441] Chlorosilane is commercially available or can be prepared by a known method.
[0442] The amount of the chlorosilane to be used is 1 to 5 equivalents, preferably 1 to 2 equivalents, based on the compound (XLV).
[0443] Examples of the base to be used include organic bases (e.g., N,N-dimethylaniline, pyridine, triethylamine, imidazole, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal hydrides (e.g., sodium hydride, potassium hydride, etc.), metal bicarbonates (e.g., sodium bicarbonate, potassium bicarbonate, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0444] Examples of the solvent to be used include hydrocarbons (e.g., hexane, benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane, etc.), ethers (e.g., diethyl ether, tetrahydrofuran, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g., acetonitrile, etc.), N,N-dimethylformamide, dimethyl sulfoxide, mixed solvents thereof, etc.
[0445] The reaction temperature is −20° C. to 100° C., preferably 0° C. to 60° C.
[0446] The reaction time is 5 minutes to 30 hours, preferably 30 minutes to 15 hours.
[0447] The compound (XLVI) protected with methoxymethyl or triphenylmethyl and the compound (XLVI) protected with tetrahydrofuranyl or 1-ethoxyethyl described above can be obtained by reacting the compound (XLV) with the corresponding halide in the presence of a base.
[0448] The corresponding halides are halomethyl methyl ether, triphenylmethyl halide, 2-halotetrahydrofuran and 1-haloethyl ether, respectively, and they are commercially available or can be prepared by a known method.
[0449] Examples of the halide to be used include chlorides, and bromides.
[0450] The amount of the halide to be used, the kind of base and solvent, and the reaction conditions, etc., are similar to those in the above reaction of the compound (XLV) with chlorosilane.
[0451] Alternatively, the compound (XLVI) protected with methoxymethyl described above can also be obtained by reacting the compound (XLV) with dimethoxymethane in the presence of an appropriate catalyst (e.g., phosphorus pentaoxide, etc.).
[0452] The solvent to be used and the reaction conditions are similar to those in the reaction of the compound (XLV) with olefin.
[0453] The compound (XLVI) thus obtained can be used in the next step as the reaction mixture or the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0454] [Route 16 (continued)]
47
[0455] wherein each symbol is as defined above.
[0456] The compound (XLVII) can be prepared by reacting the compound (XLVI) with lithium or magnesium in an appropriate solvent.
[0457] The amount of the lithium or magnesium to be used is 1 to 4 equivalents, preferably 1 to 2 equivalents, based on the compound (XLVI).
[0458] Examples of the solvent to be used include ethers such as dry THF, diethyl ether, dibutyl ether, etc. These solvents can be used alone or as mixtures with other solvents such as hydrocarbons (e.g., toluene, etc.), amines (e.g., triethylamine, etc.), etc.
[0459] The reaction temperature is room temperature to 150° C., preferably 40° C. to 100° C.
[0460] The reaction time is 10 minutes to 48 hours, preferably 30 minutes to 6 hours.
[0461] If necessary, as a reaction activating agent, a small amount of iodine, dibromoethane, ethyl bromide, etc., can be used. The amount thereof is 0.001 to 0.4 equivalent, preferably 0.005 to 0.2 equivalent.
[0462] The compound (XLVII) thus obtained can be used in the next step as the reaction mixture or the crude product.
[0463] [Route 16 (continued)]
48
[0464] wherein each symbol is as defined above.
[0465] The compound of the formula (XLVIII) can be prepared by reacting the compound (XLVII) with the compound (XII) or (XIII) in an appropriate solvent (alone or as a mixture).
[0466] The amount of the compound (XII) or (XIII) to be used in this reaction is 1 equivalent or more, preferably 1 to 3 equivalents, based on the compound (XLVII).
[0467] Examples of the solvent to be used is aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), ethers (e.g., THF, diethyl ether, dioxane, etc.), triethylamine, mixed solvents thereof, etc.
[0468] The reaction temperature is −100° C. to 100° C., preferably −80° C. to 40° C.
[0469] The reaction time varies with the kind of compound, and is 0.5 to 80 hours.
[0470] The compound (XLVIII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0471] [Route 16 (continued)]
49
[0472] wherein each symbol is as defined above.
[0473] The compound (XLIX) can be prepared by reacting the compound (XLVIII) with the compound (III) or a salt thereof in an appropriate solvent.
[0474] The amount of the compound (III) to be used is 1 to 4 equivalents, preferably 1 to 2.5 equivalents, based on the compound (XLVIII).
[0475] Examples of the salt of the compound (III) include mineral acid salts such as a hydrochloric acid salt, sulfuric acid salt, etc. When the salt is used, it is neutralized with a base for the reaction. Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, etc.), etc. The amount of the base to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the compound (III).
[0476] Examples of the solvent to be used is hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol, etc.), water, mixed solvents thereof, etc.
[0477] The reaction temperature is 0° C. to 150° C., preferably 20° C. to 100° C.
[0478] The reaction time is normally 15 minutes to 24 hours.
[0479] The compound (XLIX) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0480] [Route 16 (continued)]
50
[0481] wherein each symbol is as defined above.
[0482] The compound (XXXIX) can be obtained by deprotecting the protective group of the hydroxyl group of the compound (XLIX).
[0483] The hydroxyl group can be deprotected by a conventional method for deprotecting a protected hydroxyl group described in, e.g., T. W. Green, “Protective Groups in Organic Synthesis”, p. 1-113, John Willy & Sons (1981); C. B. Reese, “Protective Groups in Organic Chemistry”, J. F. McOmie (ed.), p.95-143, Plenum Press (1973).
[0484] For example, the deprotection can be carried out by treating the compound (XLIX) with an acid when the protective group of the hydroxyl group is alkyl (e.g., t-butyl, etc.), alkenyl (e.g., allyl, etc.), aralkyl (e.g., triphenylmethyl, etc.), trialkylsilyl (e.g., t-butyldimethylsilyl, triisopropylsilyl, etc.), alkyldiarylsilyl (e.g., t-butyldiphenylsilyl, etc.), triaralkylsilyl (e.g., tribenzylsilyl, etc.), alkoxyalkyl (e.g., methoxymethyl, l-ethoxyethyl, 1-methyl-1-methoxyethyl, etc.), alkoxyalkoxyalkyl (e.g., methoxyethoxymethyl, etc.), alkylthioalkyl (e.g., methylthiomethyl, etc.), tetrahydropyranyl (e.g., tetrahydropyran-2-yl, 4-methoxytetrahydropyran-4-yl, etc.), tetrahydrothiopyranyl (e.g., tetrahydrothiopyran-2-yl, etc.), tetrahydrofuranyl (e.g., tetrahydrofuran-2-yl, etc.), tetrahydrothiofuranyl (e.g., tetrahydrothiofuran-2-yl, etc.), aralkyloxyalkyl (e.g., benzyloxymethyl, etc.), etc.
[0485] In general, the acid to be used includes, for example, inorganic acids such as hydrohalogenic acids (e.g., hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.), hydrogen halides (e.g., hydrogen chloride, hydrogen bromide, hydrogen iodide, etc.), boric acid, phosphoric acid, sulfuric acid, etc., sulfonic acids (e.g., aliphatic sulfonic acids such as trifluoromethanesulfonic acid, etc., and aromatic sulfonic acids such as toluenesulfonic acid, etc.), carboxylic acids (e.g., acetic acid, trifluoroacetic acid, etc.), silica gel, Lewis acids [e.g., aluminium halides (e.g., aluminium chloride, etc.), zinc chloride, titanium tetrachloride, etc.], etc. One or more suitable acids can be selected from these acids to use them in the reaction.
[0486] The amount of the acid to be used is a trace amount to 1 equivalent. Alternatively, a carboxylic acid can be used as a solvent.
[0487] Examples of the solvent to be used is hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0488] The reaction temperature is −80° C. to 150° C., preferably −10° C. to 80° C.
[0489] The reaction time is 1 minute to 3 hours, preferably 5 minutes to 1 hour.
[0490] When the protective group is substituted silyl, for example, the deprotection can be carried out in basic conditions (e.g., sodium hydroxide/water-containing ethanol, etc.) or in the presence of fluoride ion (e.g., n-Bu4N+F—, C5H5N+HF—, etc.).
[0491] The compound (XXXIX) thus obtained can be used in the next step as the reaction mixture or crude product.
[0492] If necessary, the product can be purified by a conventional method (e.g., column chromatography, recrystallization, etc.).
[0493] [Route 16 (continued)]
51
[0494] wherein each symbol is as defined above.
[0495] The compound (XXXIX) can be prepared by reacting the compound (XLVIII) with the compound (III) or a salt thereof in the presence of a base in an appropriate solvent. The amount of the compound (III) to be used is 1 to 4 equivalents, preferably 1 to 2.5 equivalents, based on the compound (XLVIII).
[0496] Examples of the salt of the compound (III) include mineral acid salts such as a hydrochloric acid salt, sulfuric acid salt, etc. When the salt is used, the salt is neutralized with a base for the reaction.
[0497] Examples of the base to be used include amines (pyridine, etc.), etc. The amount of the base to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the salt of the compound (III).
[0498] Examples of the solvent to be used is hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol, etc.), water, mixed solvents thereof, etc.
[0499] The reaction temperature is 0° C. to 150° C., preferably 20° C. to 200° C.
[0500] The reaction time is normally 15 minutes to 24 hours.
[0501] The compound (XXXIX) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., column chromatography, recrystallization, etc.).
[0502] [Route 16 (continued)]
52
[0503] wherein each symbol is as defined above.
[0504] The compound (L) can be prepared by reacting the compound (XLVIII) with hydroxylamine or a salt thereof in an appropriate solvent.
[0505] The amount of the hydroxylamine to be used is 1 to 4 equivalents, preferably 1 to 2.5 equivalents, based on the compound (XLVIII).
[0506] Examples of the salt of hydroxylamine include mineral acid salts such as a hydrochloric acid salt, sulfuric acid salt, etc. When the salt is used, it is neutralized with a base for the reaction. Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, etc.), etc. The amount of the base to be used is 1 to 3 equivalents, preferably 1 to 2 equivalents, based on the salt of hydroxylamine.
[0507] Examples of the solvent to be used include hydrocarbons (e.g., benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g., chloroform, 1,2-dichloroethane, etc.), ethers (e.g., tetrahydrofuran, dioxane, etc.), alcohols (e.g., methanol, ethanol, n-propanol, isopropanol, etc.), water, mixed solvents thereof, etc.
[0508] The reaction temperature is 0° C. to 150° C., preferably 20° C. to 100° C.
[0509] The reaction time is normally 15 minutes to 24 hours.
[0510] The compound (L) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., column chromatography, recrystallization, etc.).
[0511] [Route 16 (continued)]
53
[0512] wherein each symbol is as defined above.
[0513] The compound of the formula (XLIX) can be prepared by reacting the compound (L) with the compound (XVII) in the presence of a base in an appropriate solvent (alone or as a mixture). The amount of the compound (XVII) to be used in this reaction is 1 equivalent or more, preferably 1 to 2 equivalents, based on the compound (L).
[0514] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 2 equivalents.
[0515] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0516] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C.
[0517] The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0518] The compound (XLIX) thus obtained can be used in the next step as the reaction mixture or crude product, or after purifying it by a conventional method (e.g., chromatography, recrystallization, etc.).
[0519] The compound of the formula (Il) of the present invention can be prepared according to the following Route 17.
[0520] [Route 17]
54
[0521] wherein V is oxygen, sulfur or N—R5, and R5 and the other symbols are as defined above.
[0522] The compound of the formula (Il) of the present invention can be prepared by reacting the compound (XXXVI) with the compound (LI) or a salt thereof (e.g., hydrochloric acid salt, hydrobromic acid salt, etc.) in the presence or absence of a base, or in the presence or absence of an acid, or in the presence or absence of a metal salt, in the absence of a solvent or in an appropriate solvent (alone or as a mixture) by reference to, e.g., T. W. Green, “Protective Groups in Organic Synthesis”, p. 109-151, John Willy & Sons (1981).
[0523] The amount of the compound (LI) to be used in this reaction is 1 equivalent or more, preferably 1 to 5 equivalents, based on the compound (XXXVI).
[0524] Examples of the base to be used include amines (e.g., triethylamine, etc.), etc. The amount of the base to be used is 1 equivalent or more, preferably 1 to 6 equivalents, based on the compound (XXXVI).
[0525] Examples of the acid to be used include inorganic acids (e.g., hydrochloric acid, sulfuric acid, etc.) and sulfonic acids (e.g., p-toluenesulfonic acid, etc.). The amount of the acid to be used is 0.01 to 0.5 equivalent, preferably 0.02 to 0.2 equivalent, based on the compound (XXXVI).
[0526] Examples of the metal salt to be used include potassium carbonate, zinc acetate, etc. The amount of the metal salt to be used is 0.01 to 0.5 equivalent, preferably 0.02 to 0.2 equivalent, based on the compound (XXXVI).
[0527] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), alcohols (e.g., butanol, 2-methoxyethanol, ethylene glycol, glycerol, etc.), mixed solvents thereof, etc.
[0528] The reaction temperature is 20° C. to 200° C., preferably 50° C. to 160° C.
[0529] The reaction time varies with the kind of compound, and is 0.5 to 90 hours.
[0530] If necessary, the desired compound (Il) thus obtained can be purified by a conventional method (e.g., chromatography, recrystallization, etc.).
[0531] The compound of the formula (Im) of the present invention can be prepared, for example, according to the following Route 18.
[0532] [Route 18]
55
[0533] wherein each symbol is as defined above.
[0534] The compound of the formula (LII) can be prepared by reacting the compound (XXXIXb) with a halogenating agent in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0535] Examples of the halogenating agent to be used include thionyl halides (e.g., thionyl chloride, thionyl bromide, etc.), phosphoryl halides (e.g., phosphoryl chloride, phosphoryl bromide, etc.), phosphorus halides (e.g., phosphorus pentachloride, phosphorus trichloride, phosphorus pentabromide, phosphorus tribromide, etc.), phosgene, oxalyl halides (e.g., oxalyl chloride, etc.), triphenylphosphine/carbon tetrachloride, triphenylphosphine/carbon tetrabromide, etc. The amount of the halogenating agent to be used is 1 equivalent or more.
[0536] Examples of the solvent to be used include aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), nitriles (e.g., acetonitrile, etc.), mixed solvents thereof, etc.
[0537] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 120° C.
[0538] The reaction time varies with the kind of compound, and is 0.1 to 48 hours.
[0539] The compound (LII) thus obtained can be used in the next step as the crude product, or after purifying it by a conventional method (e.g., column chromatography, recrystallization, etc.).
[0540] [Route 18 (continued)]
56
[0541] wherein each symbol is as defined above.
[0542] The compound of the formula (Im) can be prepared by reacting the compound (LII) with the compound (IX) in the presence of a base in the absence of a solvent or in an appropriate solvent (alone or as a mixture).
[0543] The amount of the compound (IX) to be used in this reaction is 1 equivalent or more based on the compound (LII).
[0544] Examples of the base to be used include metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), metal carbonates (e.g., sodium carbonate, potassium carbonate, etc.), metal alkoxides (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.), etc. The amount of the base to be used is 1 equivalent or more.
[0545] Examples of the solvent to be used include N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), aromatic hydrocarbons (e.g., toluene, benzene, xylene, etc.), saturated hydrocarbons (e.g., cyclohexane, hexane, etc.), halogenated hydrocarbons (e.g., dichloromethane, 1,2-dichloroethane, etc.), ethers (e.g., THF, dioxane, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitrites (e.g., acetonitrile, etc.), water, mixed solvents thereof, etc.
[0546] The reaction temperature is −30° C. to 150° C., preferably −10° C. to 100° C. The reaction time varies with the kind of compound, and is 0.5 to 120 hours.
[0547] If necessary, the desired compound (Im) thus obtained can be purified by a conventional method (e.g., column chromatography, recrystallization, etc.).
[0548] The compound of the formula (I) of the present invention is effective against a wide variety of phytopathogenic fungi on crop plants (e.g., rice, wheat, barley, rye, corn, common millet, millet, buckwheat, soybean, redbean, peanut, etc.), fruit trees (e.g., citrus fruits, grape, apple, pear, peach, etc.), vegetables (e.g., cucumber, eggplant, tomato, pumpkin, kidney bean, etc.), etc., or seeds thereof. It is also effective against phytopathogenic fungi in soil. The compound of the present invention shows potent fungicidal activity particularly against Pyricularia oryzae, Rhizoctonia solani, Erysiphe graminis, Sphaerotheca fuliginea, Erysiphe cichoracearum, Phytophthora infestans, Pseudoperonospora cubensis, Peronospora manshurica, Plasmopara viticola, Botrytis cinerea of vegetables, grape, etc., Pythium aphanidermatum, Sclerotinia sclerotiorum of buckwheat, soybean, colza, etc., Corticium rolfsii of soybean, redbean, potato, peanut, etc., Pseudocercosporella herpotrichoides, of cereals, etc. Therefore, the compound (I) of the present invention is useful as fungicides, particularly as agricultural fungicides.
[0549] Application of the compound (I) of the present invention may be made to plants by any conventional procedure such as atomizing, scattering or spreading of the active compound. Application may also be made through treatment of seeds of plants, soil where plants grow, soil for seeding, paddy field or water for perfusion with the active compound. Application may be performed before or after the infection with phytopathogenic fungi on plants.
[0550] The compound can be used in a conventional formulation form suitable for agricultural fungicides such as solutions, wettable powders, emulsions, suspensions, concentrated liquid preparations, tablets, granules, aerosols, powders, pastes, dusts, etc.
[0551] Such formulation form can be prepared in a conventional manner by mixing at least one compound of the present invention with an appropriate solid or liquid carrier(s) and, if necessary, an appropriate adjuvant(s) (e.g., surfactants, spreaders, dispersants, stabilizers, etc.) for improving the dispersibility and other properties of the active ingredient.
[0552] Examples of the solid carriers or diluents include botanical materials (e.g., flour, tobacco stalk powder, soybean powder, walnut-shell powder, vegetable powder, saw dust, bran, bark powder, cellulose powder, vegetable extract residue, etc.), fibrous materials (e.g., paper, corrugated cardboard, old rags, etc.), artificial plastic powders, clays (e.g., kaolin, bentonite, fuller's earth, etc.), talc, other inorganic materials (e.g., pyrophyllite, sericite, pumice, sulfur powder, active carbon, etc.), chemical fertilizers (e.g., ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.), etc.
[0553] Examples of the liquid carriers or diluents include water, alcohols (e.g., methanol, ethanol, etc.), ketones (e.g., acetone, ethyl methyl ketone, etc.), ethers (e.g., diethyl ether, dioxane, cellosolve, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, methylnaphthalene, etc.), aliphatic hydrocarbons (e.g., gasoline, kerosene, lamp oil, etc.), esters, nitriles, acid amides (e.g., dimethylformamide, dimethylacetamide, etc.), halogenated hydrocarbons (e.g., dichloroethane, carbon tetrachloride, etc.), etc.
[0554] Examples of the surfactants include alkyl sulfates, alkyl sulfonates, alkylaryl sulfonates, polyethylene glycol ethers, polyhydric alcohol esters, etc.
[0555] Examples of the spreaders or dispersants include casein, gelatin, starch powder, carboxymethyl cellulose, gum arabic, alginic acid, lignin, bentonite, molasses, polyvinyl alcohol, pine oil, agar, etc.
[0556] Examples of the stabilizers include PAP (a mixture of isopropylphosphate), tricresyl phosphate (TCP), tolu oil, epoxidized oil, surfactants, fatty acids and their esters, etc.
[0557] The composition of the present invention may contain other fungicides, insecticides, herbicides or fertilizers in addition to the above ingredients.
[0558] In general, the above composition contains at least one compound of the formula (I) of the present invention in a concentration of 1 to 95% by weight, preferably 2.0 to 80% by weight. The composition can be used as such or in a diluted form. About 1.0 g to 5 kg/hectare, preferably about 10 g to 1000 g/hectare, of the compound of the present invention is used in a concentration of normally about 1 to 5,000 ppm, preferably about 10 to 1,000 ppm.
EXAMPLES
[0559] The following Examples and Test Examples further illustrate the present invention in detail, but are not to be construed to limit the scope thereof. The 1H-NMR (CDCl3) data in Examples were determined at 270 MHz in CDCl3 using tetramethylsilane as an internal standard and indicated in δ values (ppm). The coupling constants (J) are indicated in Hz. In the data, s is a singlet, d is a doublet, t is a triplet, q is a quartet, m is a multiplet, brs is a broad singlet.
Synthesis of α-ethoxyimino-2-phenoxymethylbenzyl Chloride
[0560] Dichloroethane (50 ml), thionyl chloride (6.54 g, 0.055 mol) and dimethylformamide (0.25 ml) were added to 2-phenoxymethylbenzoic acid (11.41 g, 0.05 mol), and the mixture was stirred at 80° C. for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was dissolved in dichloromethane (25 ml). The solution was added to a mixture of ethoxyamine hydrochloride (5.85 g, 0.06 mol), pyridine (9.89 g, 0.125 mol) and dry dichloromethane (50 ml) under ice-cooling over 20 minutes, and then the resulting mixture was stirred at room temperature for 2 hours. After completion of the reaction, water (200 ml) was added, adjusted to pH<2 with conc. hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Acetonitrile (150 ml), triphenylphosphine (20.98 g, 0.08 mol) and carbon tetrachloride (24.61 g, 0.16 mol) were added to the residue, and the mixture was stirred under reflux for 1.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give α-ethoxyimino-2-phenoxymethylbenzyl chloride (13.51 g, 93.2%) as a colorless oil.
[0561]
1
H-NMR (CDCl3) δ ppm: 3.14 (3H, t, J=6.7), 4.27 (2H, q, J=6.7), 5.28 (2H, s), 6.93-7.70 (9H, m).
Synthesis of 1-(α-ethoxyimino-2-phenoxymethylbenzyl)-1H-1,2,4-triazole
[0562] Dimethylformamide (3 ml) and 60% sodium hydride (0.12 g, 3 mmol) were added to 1H-1,2,4-triazole (0.20 g, 3 mmol), and the mixture was stirred at room temperature for 10 minutes. Then α-ethoxyimno-2-phenoxymethylbenzyl chloride (0.43 g, 1.5 mmol) was added, and the mixture was stirred at 120° C. for 5 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 1-(α-ethoxyimino-2-phenoxymethylbenzyl)-1H-1,2,4-triazole (0.42 g, 86.9%) as colorless crystals. mp. 78.5-80.5° C.
[0563]
1
H-NMR (CDCl3) δ ppm: 1.35 (3H, t, J=6.7), 4.30 (2H, q, J=6.7), 4.93 (2H, s), 6.76-7.55 (9H, m), 7.94 (1H, s), 9.14 (1H, s).
Synthesis of 2-chloromethyl-α-methoxyiminobenzyl Chloride
[0564] 2-Chloromethylbenzoyl chloride (18.90 g, 0.1 mol) was dissolved in dichloromethane (50 ml). The solution was added to a mixture of methoxyamine hydrochloride (12.53 g, 0.15 mol), pyridine (19.78 g, 0.25 mol) and dry dichloromethane (150 ml) under ice-cooling over 1 hour, and then the resulting mixture was stirred at 0° C. for 2 hours. After completion of the reaction, water (300 ml) was added, adjusted to pH<2 with conc. hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in dichloromethane (200 ml), and phosphorus pentachloride (20.82 g, 0.1 mol) was added under ice-cooling over 5 minutes. The mixture was stirred at 0° C. for 1 hour. After completion of the reaction, saturated aqueous sodium bicarbonate solution (400 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-chloromethyl-α-methoxyiminobenzyl chloride (18.15 g, 83.2%) as a colorless oil.
[0565]
1
H-NMR (CDCl3) δ ppm: 4.12 (3H, s), 4.83 (2H, s), 7.40-7.62 (4H, m).
Synthesis of 2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl Chloride
[0566] 3-Chlorophenol (3.09 g, 0.024 mol), dimethylformamide (20 ml) and potassium carbonate (4.15 g, 0.03 mol) were added to 2-chloromethyl-α-methoxyiminobenzyl chloride -(4.36 g, 0.02 mol), and the mixture was stirred at room temperature for 4 days. After completion of the reaction, ether (250 ml) was added, and the mixture was washed with brine (200 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl chloride (5.66 g, 91.2%) as a colorless oil.
[0567]
1
H-NMR (CDCl3) δ ppm: 4.02 (3H, s), 5.25 (2H, s), 6.80-7.70 (8H, m).
Synthesis of 1-[2-(3-chlorophenoxymethyl)-α-methoxy-iminobenzyl]imidazole
[0568] Dimethylformamide (3 ml) and 60% sodium hydride (0.16 g, 3.9 mmol) were added to imidazole (0.27 g, 3.9 mmol), and the mixture was stirred at room temperature for 10 minutes. Then, 2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl chloride (0.40 g, 1.3 mmol) was added, and the mixture was stirred at 110° C. for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 1-[2-(3-chlorophenoxymethyl)-α-methoxyiminobenzyl]imidazole (0.29 g, 65.3%) as colorless crystals. mp. 96.5-97.5° C.
[0569]
1
H-NMR (CDCl3) δ ppm: 3.97 (3H, s), 5.00 (2H, s), 6.63-7.60 (10H, m), 7.98 (1H, s).
[0570] According to the same manner as that of the synthesis of the intermediate in Example 1 or 2, various compounds of the formula (V) of the present invention, which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds obtained in Examples 1 and 2 are also listed.
1|
|
|
57
|
NoR1R2nPhysical data
|
V-1C6H5Me01H-NMR(CDCl3) δ ppm:4.02(3H, s), 6.94-7.55(9H, m)
V-2C6H5Me11H-NMR(CDCl3) δ ppm:4.02(3H, s), 5.28(2H, s),
6.93-7.69(9H, m)
V-3C6H5Et11H-NMR(CDCl3) δ ppm:1.34(3H, t, J=6.7),
4.27(2H, q, J=6.7), 5.28(2H, s), 6.93-7.70(9H, m)
V-4C6H5Allyl11H-NMR(CDCl3) δ ppm:4.69-4.72(2H, m),
5.24-5.38(2H, m), 5.25(2H, s), 5.94-6.08(1H, m), 6.93-7.71(9H, m)
V-52-Cl—C6H4Me11H-NMR(CDCl3) δ ppm:4.07(3H, s), 5.37(2H, s), 6.88-
7.79(8H, m)
V-63-Cl—C6H4Me11H-NMR(CDCl3) δ ppm:4.02(3H, s), 5.25(2H, s),
6.80-7.70(8H, m)
V-74-Cl—C6H4Me11H-NMR(CDCl3) δ ppm:4.01(3H, s), 5.24(2H, s),
6.85-7.70(8H, m)
V-82-Me—C6H4Me11H-NMR(CDCl3) δ ppm:2.30(3H, s), 4.03(3H, s), 5.23(2H, s),
6.80-7.70(8H, m)
V-94-Me—C6H4Me11H-NMR(CDCl3) δ ppm:2.28(3H, s), 4.03(3H, s), 5.25(2H, s),
6.84(2H, d, J=8.5), 7.08(2H, d, J=8.5)
V-102-Et—C6H4Me11H-NMR(CDCl3) δ ppm:1.24(3H, t, J=7.3),
2.73(2H, q, J=7.3), 4.05(3H, s), 5.29(2H, s), 6.81-7.70(8H, m)
V-112,5-Me2—C6H3Me11H-NMR(CDCl3) δ ppm:2.25(3H, s), 2.30(3H, s), 4.05(3H, s),
5.26(2H, s), 6.65—7.70(7H, m)
V-122,6-Me2—C6H3Me11H-NMR(CDCl3) δ ppm:2.28(6h, s), 4.02(3H, s), 5.02(2H, s),
6.93-7.62(6H, m), 7.90(1H, d, J=7.9)
V-132-Cl-pyridin-3-ylMe1mp 65-66° C.
|
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl Ketone
[0571] THF (2 ml) and bromoethane (0.1 ml) were added to magnesium (0.49 g, 0.02 mol) in a stream of nitrogen, and the mixture was stirred at 50° C. for 10 minutes. Then, a mixture of 1-bromo-2-(2,5-dimethylphenoxymethyl)benzene (2.91 g, 0.01 mol) and THF (8 ml) was added at 50 to 60° C. over 30 minutes, and the mixture was stirred at 50 to 60° C. for 1 hour. After completion of the reaction, the reaction mixture was added to a mixture of 3-methylisoxazol-5-carbonyl chloride (1.45 g, 0.01 mol) and THF (15 ml) at −70 to −60° C. over 15 minutes, and then the mixture was stirred at −70 to −60° C. for 0.5 hours. After completion of the reaction, saturated aqueous ammonium chloride solution (150 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone (0.56 g, 17.4%) as colorless crystals. mp. 106-108° C.
[0572]
1
H-NMR (CDCl3) δ ppm: 2.13 (3H, s), 2.28 (3H, s), 2.38 (3H, s), 5.28 (2H, s), 6.66 (1H, s), 6.67 (1H, d, J=6.7), 6.72 (1H, s), 7.00 (1H, d, J=7.9), 7.46-7.83 (4H, m).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl Ketone O-methyloxime
[0573] n-Propanol (2 ml) and methoxyamine hydrochloride (0.25 g, 3 mmol) were added to 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone (0.33 g, 1 mmol), and the mixture was stirred under reflux for 15 hours. After completion of the reaction, water (200 ml) was added, the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.18 g, 51.4%, as colorless crystals) and isomer B (0.15 g, 42.8%, as colorless crystals) of 2-(2,5-dimethylphenoxymethyl)phenyl 3-methylisoxazol-5-yl ketone O-methyloxime. One of the isomers A and B is the E-isomer and the other is Z-isomer.
[0574] Isomer A: mp. 113-114° C.
[0575]
1
H-NMR (CDCl3) δ ppm: 2.11 (3H, s), 2.25 (3H, s), 2.33 (3H, s), 4.12 (3H, s), 4.98 (2H, s), 6.51 (1H, s), 6.64 (1H, d, J=7.3), 6.91 (1H, s), 6.97 (1H, d, J=7.3), 7.38-7.62 (4H, m).
[0576] Isomer B: mp. 107-108° C.
[0577]
1
H-NMR (CDCl3) δ ppm: 2.13 (3H, s), 2.24 (3H, s), 2.26 (3H, s), 4.04 (3H, s), 4.93 (2H, s), 5.99 (1H, s), 6.53 (1H, s), 6.65 (1H, d, J=7.9), 6.99 (1H, d, J=7.3), 7.21-7.52 (3H, m), 7.68 (1H, d, J=7.9).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl Ketone
[0578] THF (2 ml) and bromoethane (0.1 ml) were added to magnesium (0.49 g, 0.02 mol) in a stream of nitrogen, and the mixture was stirred at 50° C. for 10 minutes. Then, a mixture of 1-bromo-2-(2,5-dimethylphenoxymethyl)benzene (2.91 g, 0.01 mol) and THF (8 ml) was added at 50 to 60° C. over 30 minutes, and the mixture was stirred at 50 to 60° C. for 1 hour. After completion of the reaction, the reaction mixture was added to a mixture of 3-cyanoisoxazole (1.45 g, 0.015 mol) and THF (15 ml) at 20° C. or lower over 15 minutes, and then the mixture was stirred at room temperature for 2 hours. After completion of the reaction, 2N sulfuric acid (200 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl ketone (0.20 g, 6.3%) as colorless crystals. mp. 90.5-92° C.
[0579]
1
H-NMR (CDCl3) δ ppm: 2.16 (3H, s), 2.29 (3H, s), 5.32 (2H, s), 6.66 (1H, s), 6.67 (1H, d, J=6.7), 6.86 (1H, d, J=1.2), 7.00 (1H, d, J=7.3), 7.47 (1H, t, J=7.3), 7.60-8.03 (3H, m), 8.50 (1H, d, J=1.8).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl Ketone O-methyloxime
[0580] n-Propanol (2 ml) and methoxyamine hydrochloride (0.50 g, 6 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-phenyl isoxazol-3-yl ketone (0.64 g, 2 mmol), and the mixture was stirred under reflux for 17 hours. After completion of the reaction, water (100 ml) was added, the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (benzene/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl isoxazol-3-yl ketone O-methyloxime (a mixture of isomers A/B) (0.55 g, 81.8%) as colorless crystals. mp. 104-108° C.
[0581]
1
H-NMR (CDCl3) δ ppm: 2.13 (2.15) (3H, s), 2.23 (2.25) (3H, s), 4.01 (4.08) (3H, s), 4.95 (5.01) (2H, s), 6.52-7.00 (4H, m), 7.29-7.64 (4H, m), 8.39 (8.45) (1H, d, J=1.8).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl Ketone
[0582] Dichloroethane (20 ml), thionyl chloride (1.31 g, 0.011 mol) and dimethylformamide (0.1 ml) were added to 2-(2,5-dimethylphenoxymethyl)benzoic acid (2.56 g, 0.01 mol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure to give crude 2-(2,5-dimethylphenoxymethyl)benzoyl chloride. 1.6M n-butyllithium/n-hexane solution (6.25 ml, 0.01 mol) was added to a mixture of 1-methylpyrazole (0.99 g, 0.012 mol) and THF (10 ml) at −70 to −60° C. over 15 minutes, and then the mixture was stirred at −70° C. to room temperature for 1 hour. The reaction mixture was cooled to −70° C., and a solution of the crude 2-(2,5-dimethylphenoxymethyl)benzoyl chloride in THF (10 ml) was added, and the mixture was stirred at −70° C. for 1 hour. After completion of the reaction, 1N hydrochloric acid (100 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl ketone (0.50 g, 15.6%) as colorless crystals.
[0583] mp. 88-89° C.
[0584]
1
H-NMR (CDCl3) δ ppm: 2.04 (3H, s), 2.28 (3H, s), 4.22 (3H, s), 5.23 (2H, s), 6.50 (1H, d, J=2.4), 6.65 (1H, s), 6.66 (1H, d, J=6.7), 6.97 (1H, d, J=7.3), 7.38-7.76 (4H, m).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl Ketone O-ethyloxime
[0585] n-Propanol (2 ml) and ethoxyamine hydrochloride (0.18 g, 1.8 mmol) were added to 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl ketone (0.20 g, 0.6 mmol), and the mixture was stirred under reflux for 3 days. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.11 g, 50.4%, as colorless crystals) and isomer B (0.10 g, 45.9%, as colorless crystals) of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methylpyrazol-5-yl ketone O-ethyloxime.
[0586] Isomer A: mp. 74-76° C.
[0587]
1
H-NMR (CDCl3) δ ppm: 1.30 (3H, t, J=7.3), 2.13 (3H, s), 2.23 (3H, s), 4.13 (3H, s), 4.24 (2H, q, J=7.3), 4.95 (2H, s), 5.92 (1H, d, J=2.4), 6.51 (1H, s), 6.64 (1H, d, J=7.9), 6.99 (1H, d, J=7.3), 7.17-7.64 (5H, m).
[0588] Isomer B: mp. 84-86° C.
[0589]
1
H-NMR (CDCl3) δ ppm: 1.33 (3H, t, J=6.7), 2.23 (3H, s), 2.29 (3H, s), 3.68 (3H, s), 4.29 (2H, q, J=6.7), 5.14 (2H, s), 6.30 (1H, d, J=1.8), 6.58 (1H, s), 6.68 (1H, d, J=7.3), 7.03 (1H, d, J=7.3), 7.16-7.47 (3H, m), 7.52 (1H, d, J=1.8), 7.73 (1H, d, J=7.9).
[0590] According to the same manner as that of the syntheses of the intermediates in Examples 3 to 5, various compounds of the formula (XIV) of the present invention, which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds obtained in Examples 3 to 5 are also listed.
2|
|
|
58
|
NoR1R3nPhysical data
|
XIV-1C6H51-Me-imidazol-01H-NMR(CDCl3) δ ppm:3.94(3H, s),
2-yl6.92-7.30(7H, m), 7.43(H, td, J=8.6,
1.8), 7.64(1H, dd, J=7.9, 1.8)
XIV-22,5-Me2pl —C6H31-Me-imidazol-11H-NMR(CDCl3) δ ppm:2.07(3H, s),
2-yl2.26(3H, s), 4.01(3H, s), 5.23(2H, s),
6.00(1H, s), 6.64(1H, d, J=7.3),
6.97(1H, d, J=7.3), 7.05(1H, s),
7.19(1H, s), 7.40-7.83(4H, m)
XIV-3C6H5Isoxazol-3-yl11H-NMR(CDCl3) δ ppm:5.34(2H, s),
6.85-7.28(6H, m), 7.46(1H, t, J=7.3),
7.61(1H, td, J=7.9, 1.2), 7.74(1H, d,
J=7.9), 7.99(1H, dd, J=7.3, 1.2),
8.50(1H, dd, J=1.2)
XIV-42-Me—C6H4Isoxazol-3-yl11H-NMR(CDCl3) δ ppm:2.21(3H,s),
5.34(2H, s), 6.80-7.14(5H, m), 7.44-
8.02(4H, m), 8.49(1H, d, J=1.2)
XIV-52,5-Me2—C6H3Isoxazol-3-yl1mp 90.5-92° C.
XIV-6C6H55-Me-isoxazol-11H-NMR(CDCl3) δ ppm:2.49(3H, s),
3-yl5.34(2H, s), 6.46(1H, d, J=1.2), 6.88-
7.99(9H, m)
XIV-72,5-Me2—C6H35 Me-11H-NMR(CDCl3) δ ppm:2.17(3H, s),
isoxazol-3-yl2.28(3H, s), 2.49(3H, s), 5.32(2H, s),
6.46(1H, s), 6.66-7.02(3H, m), 7.42-
8.00(4H, m)
XIV-82-Me—C6H43-Me-11H-NMR(CDCl3) δ ppm:2.18(3H, s),
isoxazol-5-yl2.38(3H, s), 5.30(2H, s), 6.71(1H, s),
6.81-7.80(8H, m)
XIV-92,5-Me2—C6H33-Me-1mp 106-108° C.
isoxazol-5-yl
XIV-102,5-Me2—C6H32-Isoxazolin-11H-NMR(CDCl3) δ ppm:2.17(3H, s),
3-yl2.31(3H, s), 3.20(2H, t, J=11.0),
4.42(2H, t, J=11.0), 5.20(2H, s), 6.68-
7.84(7H, m)
XIV-112,5-Me2—C6H35,5-Me2-2-11H-NMR(CDCl3) δ ppm:1.35(6H, s),
isoxazolin-3-yl2.16(3H, s), 2.30(3H, s), 2.96(2H, s),
5.22(2H, s), 6.67-7.80(7H, m)
XIV-122,5-Me2—C6H31-Me-1mp 88-89° C.
pyrazol-5-yl
XIV-132,5-Me2—C6H32-Furyl11H-NMR(CDCl3) δ ppm:2.10(3H, s),
2.26(3H, s), 5.25(2H, s), 6.55-
6.67(3H, m), 6.97(1H, d, J=7.3),
7.06(1H, d, J=3.7), 7.39-7.80(5H, m)
XIV-142,5-Me2—C6H3Thiazol-2-yl11H-NMR(CDCl3) δ ppm:2.11(3H, s),
2.27(3H, s), 5.30(2H, s), 6.64(1H, s),
6.65(1H, d, J=2.5), 6.98(1H, d, J=7.9),
7.45-8.10(6H, m)
XIV-152,5-Me2—C6H33-Me-11H-NMR(CDCL3) δ ppm:2.07(3H, s),
isothiazol-5-yl2.27(3H, s), 2.53(3H, s), 5.25(2H, s),
6.60-7.82(8H, m)
XIV-164-Cl-2-Me—C6H35-Me-1mp 103-104° C.
isoxazol-3-yl
XIV-173-Me-C6H4Isoxazol-3-yl11H-NMR(CDCl3) δ ppm:2.30(3H, s),
5.32(2H, s), 6.66-6.77(3H, m),
6.87(1H, s), 7.12(1H, t, J=7.3), 7.46-
7.76(3H, m), 8.00(1H, d, J=7.9),
8.50(1H, s)
XIV-184-Me-C6H4Isoxazol-3-yl11H-NMR(CDCl3) δ ppm:2.26(3H, s),
5.30(2H, s), 6.77(2H, d, J=8.6),
6.86(1H, d, J=1.8), 7.04(2H, d,
J=8.6), 7.45-7.98(4H, m), 8.50(1H, d,
J=1.8)
XIV-192-Cl-C6H4Isoxazol-3-yl1mp 92.0-93.0° C.
XIV-203-Cl-C6H4Isoxazol-3-yl1mp 75.0-76.0° C.
XIV-214-Cl-C6H4Isoxazol-3-yl11H-NMR(CDCl3) δ ppm:5.32(2H, s),
6.80-6.83(2H, m), 6.86(1 H, d, J=1.8),
7.19-7.22(2H, m), 7.45-8.02(4H, m),
8.52(1H, d, J=1.2)
XIV-223-CF3—C6H4Isoxazol-3-yl11H-NMR(CDCl3) δ ppm:5.38(2H, s),
6.87(1H, d, J=1.8), 7.04-7.75(7H, m),
8.04(1H, d, J=7.9), 8.52(1H, d,
J=1.8)
XIV-234-Cl-2-Me—C6H3Isoxazol-3-yl1mp 107.0-108.0° C.
XIV-242-Me—C6H45-Me-1mp 77.5-78.5° C.
isoxazol-3-yl
XIV-253-Me—C6H45-Me-11H-NMR(CDCl3) δ ppm:2.30(3H, s),
isoxazol-3-yl2.49(3H, s), 5.32(2H, s), 6.47(1H, d,
J=1.2), 6.67-6.85(3H, m), 7.12(1H, t,
J=7.3), 7.41-7.98(4H, m)
XIV-264-Me—C6H45-Me-11H-NMR(CDCl3) δ ppm:2.26(3H, s),
isoxazol-3-yl12.49(3H, s), 5.30(2H, s), 6.46(1H, s),
6.77-6.80(2H, m), 7.05(2H, d, J=7.9),
7.40-7.97(4H, m)
XIV-272-Cl—C6H45-Me-1mp 93.5-94.5° C.
isoxazol-3-yl
XIV-283-CL—C6H45-Me-1mp 72.0-73.0° C.
isoxazol-3-yl
XIV-294-Cl—C6H45-Me-1mp 95.0-96.0° C.
isoxazol-3-yl
XIV-303-CF3—C6H45-Me-1mp 58.5-59.5° C.
isoxazol-3-yl
XIV-314-Ph—C6H45-Me-1mp 116.5-117.5° C.
isoxazol-3-yl
XIV-322-Me—C6H4Isoxazol-5-yl1mp 67.5-68.5° C.
XIV-332,5-Me2—C6H3Isoxazol-5-yl1mp 103.5-105.0° C.
XIV-344-Cl-2-Me—C6H3Isoxazol-5-yl1mp 109.5-111.0° C.
XIV-35C6H53-Me-01H-NMR(CDCl3) δ ppm:2.30(3H, s),
isoxazol-5-yl6.76(1H, s), 6.91(1H, d, J=7.3), 6.99-
7.51(7H, m), 7.63(1H, dd, J=7.3, 1.8)
XIV-363-Me—C6H43-Me-1mp 68.0-69.0° C.
isoxazol-5-yl
XIV-372-Cl—C6H43-Me-1mp 104.0-105.0° C.
isoxazol-5-yl
XIV-383-Cl—C6H43-Me-1mp 92.5-93.5° C.
isoxazol-5-yl
XIV-393-CF3—C6H43-Me-1mp 80.5-81.5° C.
isoxazol-5-yl
XIV-404-Cl-2-Me—C6H33-Me-1mp 125.5-126.5° C.
isoxazol-5-yl
XIV-414-Ph—C6H43-Me-1mp 127.0-128.0° C.
isoxazol-5-yl
XIV-42C6H51-Me-11H-NMR(CDCl3) δ ppm:4.01(3H, s),
imidazol-2-yl5.24(2H, s), 6.80-6.83(2H, m),
6.91(1H, t, J=7.3), 7.04(1H, s), 7.18-
7.81(7H, m)
XIV-432-Me—C6H41-Me-11H-NMR(CDCl3) δ ppm:2.13(3h, s),
imidazol-2-yl4.01(3H, s), 5.25(2H, s), 6.78-6.85(2H,
m), 7.05(1H, s), 7.10(1H, d, J=7.3),
7.18(1H, s), 7.39-7.83(4H, m)
XIV-443-Me—C6H41-Me-11H-NMR(CDCl3) δ ppm:2.28(3H, s),
imidazol-2-yl4.01(3H, s), 5.21(2H, s), 6.59-6.74(3H,
m), 7.04(1H, s), 7.09(1H, t, J=7.9),
7.18(1H, s), 7.39-7.80(4H, m)
XIV-454-Me—C6H41-Me-11H-NMR(CDCl3) δ ppm:2.25(3H, s),
imidazol-2-yl4.02(3H, s), 5.20(2H, s), 6.69-6.72(2H,
m), 6.99-7.02(2H, m), 7.05(1H, s),
7.18(1H, s), 7.38-7.79(4H, m)
XIV-462-Cl—C6H41-Me-1mp 87.0-88.0° C.
imidazol-2-yl
XIV-473-Cl—C6H41-Me-11H-NMR(CDCl3) δ ppm:4.03(3h, S),
imidazol-2-yl5.23(2H, s), 6.70(1H, dd, J=8.6, 1.8),
6.82(1H, t, J=1.8), 6.90(1H, dd, J=7.3,
1.2), 7.06(1H, s), 7.13(1H, t, J=7.9),
7.19(1H, d, J=1.2), 7.40-7.81(3H, m)
XIV-484-Cl—c6H41-Me-11H-NMR(CDCl3) δ ppm:4.03(3H, s),
imidazol-2-yl5.22(2H, s), 6.73-6.78(2H, m),
7.06(1H, s), 7.13-7.59(6H, m),
7.80(1H, dd, J=7.3, 1.2)
XIV-492,4-Cl2—C6H31-Me-1mp 141.0-142.0°0 C.
imidazol-2-yl
XIV-503,4-Cl2—C6H31-Me-1mp 78.0-79.0° C.
imidazol-2-yl
XIV-514-Cl-2-Me—C6H31-Me-1mp 101.0-102.0° C.
imidazol-2-yl
XIV-523-CF3—C6H41-Me-11H-NMR(CDCl3) δ ppm:4.01(3H, s),
imidazol-2-yl5.28(2H, s), 6,97-7.61(9H, m),
7.80(1H, dd, J=7.9, 1.8)
XIV-532-MeO—C6H41-Me-1mp 88.0-89.0° C.
imidazol-2-yl
XIV-543-MeO—C6H41-Me-11H-NMR(CDCl3) δ ppm:3.74(3H, s),
imidazol-2-yl4.02(3H, s), 5.21(2H, s), 6.38-6.50(3H,
m), 7.05(1H, s), 7.11(1H, t, J=7.9),
7.18(1H, s), 7.42-7.79(4H, m)
XIV-554-F—C6H41-Me-11H-NMR(CDCl3) δ ppm:4.03(3H, s),
imidazol-2-yl5.21(2H, s), 6.72-6.95(4H, m),
7.06(1H, s), 7.18(1H, d, J=1.2), 7.42-
7.80(4H, m)
XIV-563-i-Pr—C6H41-Me-11H-NMR(CDCl3) δ ppm:1.20(6H, d,
imidazol-2-ylJ=7.3), 2.83(1H, sept, J=7.3), 4.00(3H,
s), 5.21(2H, s), 6.60-6.80(3H, m),
7.03(1H, s), 7.11-7.79(6H, m)
XIV-574-Ph—C6H41-Me-11H-NMR(CDCl3) δ ppm:4.03(3H, s),
imidazol-2-yl5.28(2H, s), 6.87-6.90(2H, m),
7.06(1H, s), 7.19(1H, s), 7.28-
7.84(11H, m)
XIV-58C6H53,5-Me2-11H-NMR(CDCl3) δ ppm:2.17(3H, s),
isoxazol-4-yl2.25(3H, s), 5.19(2H, s), 6.78—6.82(2H,
m), 6.93(1H, t, J=7.3), 7.21-7.67(6H, m)
XIV-592,5-Me2—C6H33,5-Me2-1mp 109.0-110.5° C.
isoxazol-4-yl
XIV-602-Me—C6H33-Me-2-isoxazolin-11H-NMR(CDCl3) δ ppm:2.02(3H, s),
5-yl2.32(3H, s), 3.08(1H, m), 3.53-
3.62(1H, m), 5.33-5.46(2H, m),
5.69(1H, dd, J=11.6, 6.7), 6.88(1H, s),
6.91(1H, s), 7.15(1H, t, J=8.5), 7.43-
8.01(4H, m)
XIV-612,5-Me2—C6H33-Me-2-isoxazolin-1mp 88.0-90.0° C.
5-yl
XIV-62C6H54-Me-1,2,3-11H-NMR(CDCl3) δ ppm 2.77(3H, s),
thiadiazol-5-yl5.26(2H, s), 6.76(1H, s), 6.79(1H, d,
J=1.2), 6.94(1H, t, J=7.3), 7.21-
7.74(6H, m)
XIV-632,5-Me2—C6H34-Me-1,2,3-1mp 98.5-99.5° C.
thiadiazol-5-yl
XIV-642-Me—C6H45-Me-2-isoxazolin-1
3-yl
XIV-65C6H55-Me-2-isoxazolin-1
3-yl
XIV-664-Cl—C6H45-Me-2-isoxazolin-1
3-yl
XIV-673-CF3—C6H45-Me-2-isoxazolin-1
3-yl
XIV-684-Cl-2-Me—C6H35-Me-2-isoxazolin-1
3-yl
XIV-694-Cl—C6H42-Isoxazolin-3-yl1
XIV-703-CF3—C6H42-Isoxazolin-3-yl1
XIV-714-Cl-2-Me—C6H32-Isoxazolin-3-yl1
XIV-722-Me—C6H42-Isoxazolin-3-yl1
XIV-73C6H52-Isoxazolin-3-yl0
XIV-74C6H5Isoxazol-3-yl0
|
Synthesis of 2-(4-chlorophenoxymethyl)phenyl 1-methyl-1H-1,2,4-triazol-5-yl Ketone O-methyloxime
[0591] Dimethylformamide dimethylacetal (0.53 g, 4.5 mmol) was added to 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetamide (0.48 g, 1.5 mmol), and the mixture was stirred under reduced pressure (ca. 40 mmHg) at 60° C. for 0.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and a mixture of methylhydrazine (0.08 g, 1.8 mmol) and acetic acid (3 ml) was added to the residue. The mixture was stirred at 90° C. for 1 hour. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (100 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 1-methyl-1H-1,2,4-triazol-5-yl ketone O-methyloxime (0.31 g, 57.9%) as colorless crystals.
[0592] mp. 113-114° C.
[0593]
1
H-NMR (CDCl3) δ ppm: 4.01 (3H, s), 4.08 (3H, s), 4.91 (2H, s), 6.67-6.70 (2H, m), 7.15-7.18 (2H, m), 7.26-7.54 (4H, m), 7.83 (1H, s).
[0594] Example 7
Synthesis of 2-(4-chlorophenoxymethyl)-N-hydroxyaminomethylene-α-methoxyiminophenylacetamide
[0595] Dimethylformamide dimethylacetal (0.53 g, 4.5 mmol) was added to 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetamide (0.48 g, 1.5 mmol), and the mixture was stirred under reduced pressure (ca. 40 mmHg) at 60° C. for 0.5 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, and a mixture of aqueous 50% hydroxylamine solution (0.20 g, 2 mmol) and acetic acid (3 ml) was added to the residue under ice-cooling. The mixture was stirred at room temperature for 1 hour. After completion of the reaction, ethyl acetate (150 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (100 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)-N-hydroxyaminomethylene-α-methoxyiminophenylacetamide (0.41 g, 75.6%) as colorless crystals.
[0596] mp. 185-186° C. (decomposition)
[0597]
1
H-NMR (CDCl3) δ ppm: 4.00 (3H, s), 4.93 (2H, s), 6.76-6.80 (2H, m), 6.86 (1H, d, J=8.5), 7.18-7.22 (2H, m), 7.37-7.52 (3H, m), 7.70 (1H, d, J=10.4), 9.50 (1H, d, J=9.8).
Synthesis of 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-5-yl Ketone O-methyloxime
[0598] Dioxane (2 ml) and acetic acid (1.5 ml) were added to 2-(4-chlorophenoxymethyl)-N-hydroxyaminomethylene-α-methoxyiminophenylacetamide (0.36 g, 1 mmol), and the mixture was stirred at 120° C. for 4 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (100 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.14 g, 40.8%) as colorless crystals.
[0599] mp. 96-97.5° C.
[0600]
1
H-NMR (CDCl3) δ ppm: 4.09 (3H, s), 4.94 (2H, s), 6.66-6.70 (2H, m), 7.14-7.17 (2H, m), 7.28-7.60 (4H, m), 8.44 (1H, s).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl Ketone O-methyloxime
[0601] Dichloroethane (5 ml), thionyl chloride (0.65 g, 5.5 mmol) and dimethylformamide (0.05 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetic acid (1.57 g, 5 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, pyridine (3 ml) and 1-hydroxyimino-1-propylamine (0.88 g, 10 mmol) were added to the residue, and the mixture was stirred under reflux for 0.5 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with IN hydrochloric acid (150 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 3-ethyl-1,2,4-oxadiazol-5-yl ketone O-methyloxime (0.63 g, 34.5%) as colorless crystals.
[0602] mp. 111.5-112.5° C.
[0603]
1
H-NMR (CDCl3) δ ppm: 1.30 (3H, t, J=7.3), 2.09 (3H, s), 2.25 (3H, s), 2.77 (2H, q, J=7.3), 4.11 (3H, s), 4.95 (2H, s), 6.54 (1H, s), 6.65 (1H, d, J=7.9), 6.98 (1H, d, J=7.3), 7.27-7.66 (4H, m).
Synthesis of 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetohydrazide
[0604] Methanol (10 ml), THF (10 ml) and hydrazine monohydrate (1.68 g, 0.03 mol) were added to methyl 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetate (3.27 g, 0.01 mol), and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, water (200 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetohydrazide (2.93 g, 89.6%) as colorless crystals.
[0605] mp. 124.5-126° C.
[0606]
1
H-NMR (CDCl3) δ ppm: 2.18 (3H, s), 2.29 (3H, s), 3.88 (2H, d, J=4.3), 3.96 (3H, s), 4.92 (2H, s), 6.61 (1H, s), 6.67 (1H, d, J=7.3), 7.01 (1H, d, J=7.3), 7.21-7.59 (4H, m), 7.76 (1H, brs).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1,3,4-oxadiazol-2-yl Ketone O-methyloxime
[0607] Ethyl orthoformate (2 ml) was added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetohydrazide (0.49 g, 1.5 mmol), and the mixture was stirred under reflux for 4 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 1,3,4-oxadiazol-2-yl ketone O-methyloxime (0.10 g, 19.8%) as colorless crystals.
[0608] mp. 134-135° C.
[0609]
1
H-NMR (CDCl3) δ ppm: 2.08 (3H, s), 2.25 (3H, s), 4.08 (3H, s), 4.96 (2H, s), 6.54 (1H, s), 6.65 (1H, d, J=7.3), 6.97 (1H, d, J=7.9), 7.32-7.64 (4H, m), 8.93 (1H, s).
Synthesis of α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime
[0610] 28% sodium methoxide/methanol solution (1.31 g, 6.8 mmol) was added to a mixture of hydroxylamine hydrochloride (0.47 g, 6.8 mmol) and methanol (10 ml) under ice-cooling over 5 minutes. Then, 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (1.02 g, 3.4 mmol) was added, and the mixture was stirred under reflux for 1.5 hours. After completion of the reaction, water (200 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime (0.87 g, 76.7%) as colorless crystals.
[0611] mp. 200° C. (decomposition)
[0612]
1
H-NMR (CDCl3) δ ppm: 3.92 (3H, s), 4.93 (2H, s), 5.04 (2H, brs), 6.79-6.87 (2H, m), 7.15-7.21 (3H, m), 7.33-7.52 (3H, m).
Synthesis of 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-3-yl Ketone O-methyloxime
[0613] Ethyl orthoformate (2 ml) was added to α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime (0.40 g, 1.2 mmol), and the mixture was stirred under reflux for 4 hours. After completion of the reaction, toluene (10 ml) was added, and the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.36 g, 87.3%) as colorless crystals.
[0614] mp. 107-108° C.
[0615]
1
H-NMR (CDCl3) δ ppm: 4.08 (3H, s), 4.96 (2H, s), 6.72-6.75 (2H, m), 7.14-7.18 (2H, m), 7.28-7.60 (4H, m), 8.76 (1H, s).
Synthesis of 2-(4-chlorophenoxymethyl)phenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime
[0616] Acetic anhydride (2 ml) was added α-amino-2-(4-chlorophenoxymethyl)-α-hydroxyiminoacetophenone O-methyloxime (0.40 g, 1.2 mmol), and the mixture was stirred under reflux for 5 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, ether (100 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (50 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(4-chlorophenoxymethyl)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.35 g, 81.5%) as colorless crystals.
[0617] mp. 125-126° C.
[0618]
1
H-NMR (CDCl3) δ ppm: 2.65 (3H, s), 4.07 (3H, s), 4.96 (2H, s), 6.74-6.77 (2H, m), 7.15-7.18 (2H, m), 7.26-7.59 (4H, m).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1H-tetrazol-5-yl Ketone O-methyloxime
[0619] Sodium azide (1.30 g, 20=mol), ammonium chloride (1.07 g, 20 mmol) and dimethylformamide (10 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetonitrile (0.59 g, 2 mmol), and the mixture was stirred at 115° C. for 9 hours. After completion of the reaction, ethyl acetate (150 ml) was added, and the mixture was washed with saturated brine (100 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 1H-tetrazol-5-yl ketone O-methyloxime (0.59 g, 87.4%) as colorless crystals.
[0620] mp. 168-170° C.
[0621]
1
H-NMR (CDCl3) δ ppm: 2.00 (3H, s), 2.25 (3H, s), 4.05 (3H, s), 4.95 (2H, s), 6.52 (1H, s), 6.65 (1H, d, J=7.3), 6.96 (1H, d, J=7.3), 7.32-7.63 (4H, m).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1-methyl-1H-tetrazol-5-yl Ketone O-methyloxime and 2-(2,5-dimethylphenoxymethyl)phenyl 2-methyl-2H-tetrazol-5-yl Ketone O-methyloxime
[0622] Dimethylformamide (3 ml) and potassium carbonate (0.33 g, 2.4 mmol) were added to 2-(2,5-dimethylphenoxymethyl)phenyl 1H-tetrazol-5-yl ketone O-methyloxime (0.40 g, 1.2 mmol), and the mixture was stirred at room temperature for 5 minutes. Then, dimethyl sulfate (0.23 g, 1.8 mmol) was added under ice-cooling, and the mixture was stirred at room temperature overnight. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with brine (50 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl 1-methyl-1H-tetrazol-5-yl ketone O-methyloxime as colorless crystals (0.16 g, 37.9%) [mp. 115.5-116.5° C.; 1H-NMR (CDCl3) δ ppm: 1.97 (3H, s), 2.26 (3H, s), 4.06 (3H, s), 4.13 (3H, s), 4.89 (2H, s), 6.50 (1H, s), 6.65 (1H, d, J=7.9), 6.97 (1H, d, J=7.9), 7.34-7.58 (4H, m)] and 2-(2,5-dimethylphenoxymethyl)phenyl 2-methyl-2H-tetrazol-5-yl ketone O-methyloxime as colorless crystals (0.08 g, 19.0%) [mp. 131-132° C.; 1H-NMR (CDCl3) δ ppm: 2.12 (3H, s), 2.24 (3H, s), 4.09 (3H, s), 4.34 (3H, s), 4.96 (2H, s), 6.54 (1H, s), 6.64 (1H, d, J=7.9), 6.98 (1H, d, J=7.3), 7.29-7.53 (3H, m), 7.69 (1H, d, J=7.3)].
Synthesis of 2-(3-chlorophenoxymethyl)phenyl 1-methyl-2-imidazolin-2-yl Ketone O-methyloxime
[0623] Xylene (5 ml) and benzene (5 ml) were added to 2-(3-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (1.0 g, 3.3 mmol), N-methylethylenediamine (740 mg, 10 mmol) and zinc acetate dihydrate (100 mg, 0.46 mmol), and the mixture was subjected to azeotropic dehydration and stirred at 140° C. for 18 hours. After allowing the mixture to stand for cooling, ethyl acetate was added to the reaction mixture. The mixture was washed successively with water and saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on activated alumina containing water (5%) (ethyl acetate/n-hexane) and column chromatography on silica gel (ethyl acetate/n-hexane) to give isomer A (720 mg, 60%, as an oil) and isomer B (220 mg, 19%, as an oil) of 2-(3-chlorophenoxymethyl)phenyl 1-methyl-2-imidazolin-2-yl ketone O-methyloxime.
[0624] Isomer A: 1H-NMR (CDCl3) δ ppm: 2.75 (3H, s), 3.41 (2H, t, J=9.8), 3.92 (2H, t, J=9.8), 3.97 (3H, s), 5.35 (2H, s), 6.84 (1H, ddd, J=8.0, 2.4, 0.9), 6.93 (1H, ddd, J=8.0, 1.8, 0.9), 6.99 (1H, dd, J=2.4, 1.8), 7.19 (1H, t, J=8.0), 7.32-7.44 (2H, m), 7.51 (1H, dd, J=7.3, 1.4), 7.64 (1H, d, J=7.0).
[0625] Isomer B: 1H-NMR (CDCl3) δ ppm: 3.03 (3H, s), 3.38 (2H, t, J=9.9), 3.77 (2H, t, J=9.9), 3.97 (3H, s), 4.99 (2H, s), 6.83 (1H, dd, J=8.5, 2.5), 6.91 (1H, d, J=7.8), 6.94 (1H, brs), 7.16 (1H, dd, J=8.3, 7.8), 7.23 (1H, d, J=7.6), 7.34-7.39 (2H, m), 7.49 (1H, d, J=6.4).
Synthesis of 2-(3-methylphenoxymethyl)phenyl 2-oxazolin-2-yl Ketone O-methyloxime
[0626] Ethylene glycol (2 ml) and benzene (10 ml) were added to 2-(3-methylphenoxymethyl)-α-methoxyiminophenylacetonitrile (1.0 g, 3.6 mmol), 2-aminoethanol (400 mg, 6.6 mmol) and zinc acetate dihydrate (100 mg, 0.46 mmol), and the mixture was subjected to azeotropic dehydration and stirred at 100° C. for 20 hours. After allowing the mixture to stand for cooling, ethyl acetate was added to the reaction mixture. The mixture was washed successively with water and saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2-(3-methylphenoxymethyl)phenyl 2-oxazolin-2-yl ketone O-methyloxime (280 mg, 24%) as an oil.
[0627]
1
H-NMR (CDCl3) δ ppm: 2.31 (3H, s), 4.00 (2H, t, J=9.8), 4.03 (3H, s), 4.32 (2H, t, J=9.8), 5.21 (2H, s), 6.72-6.78 (3H, m), 7.14 (1H, t, J=7.6), 7.31-7.48 (3H, m), 7.62 (1H, d, J=7.6).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 2-thiazolin-2-yl Ketone O-methyloxime
[0628] 2-Aminoethanethiol hydrochloride (2.80 g, 24.6 mmol), zinc acetate dihydrate (600 mg, 2.7 mmol), toluene (12 ml) and triethylamine (3.12 g, 30.8 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetonitrile (6.00 g, 20.4 mmol), and the mixture was stirred under reflux for 14 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl 2-thiazolin-2-yl ketone O-methyloxime (5.71 g, 79.0%) as crystals.
[0629] mp. 79-82° C.
[0630]
1
H-NMR (CDCl3) δ ppm: 2.24 (2.23) (3H, s), 2.29 (2.28) (3H, s), 3.21 (3.27) (2H, t, J=8.6), 4.07 (4.02) (3H, s), 4.24 (3.36) (2H, t, J=8.6), 5.11 (4.93) (2H, s), 6.56-7.63 (7H, m).
Synthesis of 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde
[0631] 1M diisobutylaluminum hydride/toluene solution (5.5 ml, 5.5 mmol) was added dropwise to a mixture of methyl 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetate (1.64 g, 5 mmol) and dichloromethane (15 ml) at −70° C. over 0.5 hours, and then the mixture was stirred at −70° C. to room temperature for 3 hours. Methanol (3 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The precipitated insoluble materials were removed, and the mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde (0.54 g, 36.3%) as a colorless oil.
[0632]
1
H-NMR (CDCl3) δ ppm: 2.16 (3H, s), 2.28 (3H, s), 4.11 (3H, s), 4.86 (2H, s), 6.55 (1H, s), 6.67 (1H, d, J=7.3), 6.99-7.58 (5H, m), 9.69 (1H, s).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl. oxazol-5-yl Ketone O-methyloxime
[0633] p-Toluenesulfonylmethylisocyanide (0.23 g, 1.2 mmol), potassium carbonate (0.18 g, 1.3 mmol) and methanol (2 ml) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde (0.30 g, 1 mmol), and the mixture was stirred under reflux for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 2-(2,5-dimethylphenoxymethyl)phenyl oxazol-5-yl ketone O-methyloxime (0.15 g, 44.6%) as colorless crystals.
[0634] mp. 90-91° C.
[0635]
1
H-NMR (CDCl3) δ ppm: 2.12 (3H, s), 2.24 (3H, s), 4.01 (3H, s), 4.96 (2H, s), 6.54 (1H, s), 6.65 (1H, d, J=7.3), 6.88 (1H, s), 6.98 (1H, d, J=7.3), 7.24-7.69 (4H, m), 7.94 (1H, s).
Synthesis of 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl Ketone O-methyloxime
[0636] Zinc acetate dihydrate (400 mg, 1.8 mmol), ethanolamine (975 mg, 15.9 mol) and xylene (8 ml) were added to 2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile (4.00 g, 13.3 mmol), and the mixture was stirred under reflux for 63 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (1.31 g, 28.6%, as crystals) and isomer B (0.45 g, 9.8%, as crystals) of 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime.
[0637] Isomer A: mp. 97-100° C.
[0638]
1
H-NMR (CDCl3) δ ppm: 3.73 (2H, t, J=7.9), 3.96 (2H, t, J=7.9), 4.07 (3H, s), 5.00 (2H, s), 6.92-7.65 (8H, m).
[0639] Isomer B: mp. 109-112° C.
[0640]
1
H-NMR (CDCl3) δ ppm: 3.92 (2H, t, J=9.8), 4.02 (3H, s), 4.39 (2H, t, J=9.8), 5.07 (2H, s), 6.94-7.46 (8H, m).
Synthesis of 2-hydroxyphenyl 2-oxazolin-2-yl Ketone O-methyloxime
[0641] Anisole (152 ml) and aluminium chloride (16.3 g, 122 mmol) were added to 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (19.08 g, 55.3 mmol), and the mixture was stirred under ice-cooling for 1.5 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (6.82 g, 56%) as an oil.
[0642]
1
H-NMR (CDCl3) δ ppm: 4.07 (3H, s), 4.15 (2H, t, J=9.5), 4.50 (2H, t, J=9.5), 6.85-7.35 (5H, m).
Synthesis of 2-(5-trifluoromethyl-2-pyridyloxy)-phenyl 2-oxazolin-2-yl Ketone O-methyloxime
[0643] DMF (2.2 ml), potassium carbonate (210 mg, 1.5 mmol) and 2-chloro-5-trifluoromethylpyridine (220 mg, 1.2 mmol) were added to 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (220 mg, 1.0 mmol), and the mixture was stirred at 100° C. for 2.5 hours. After completion of the reaction, 1N NaOH (100 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(5-trifluoromethyl-2-pyridyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (190 mg, 52.1%) as an oil.
[0644]
1
H-NMR (CDCl3) δ ppm: 3.78 (2H, t, J=9.8), 3.98 (3H, s), 4.16 (2H, t, J=9.8), 6.94-7.87 (6H, m), 8.43 (1H, brs).
[0645] Isomer A: mp. 97-100° C.
[0646]
1
H-NMR (CDCl3) δ ppm: 3.73 (2H, t, J=7.9), 3.96 (2H, t, J=7.9), 4.07 (3H, s), 5.00 (2H, s), 6.92-7.65 (8H, m).
[0647] Isomer B: mp. 109-112° C.
[0648]
1
H-NMR (CDCl3) δ ppm: 3.92 (2H, t, J=9.8), 4.02 (3H, s), 4.39 (2H, t, J=9.8), 5.07 (2H, s), 6.94-7.46 (8H, m).
Synthesis of 2-hydroxyphenyl 2-oxazolin-2-yl Ketone O-methyloxime
[0649] Anisole (152 ml) and aluminium chloride (16.3 g, 122 mmol) were added to 2-(4-chlorobenzyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (19.08 g, 55.3 mmol), and the mixture was stirred under ice-cooling for 1.5 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (6.82 g, 56.0%) as an oil.
[0650]
1
H-NMR (CDCl3) δ ppm: 4.07 (3H, s), 4.15 (2H, t, J=9.5), 4.50 (2H, t, J=9.5), 6.85-7.35 (5H, m).
Synthesis of 2-(5-trifluoromethyl-2-pyridyloxy)-phenyl 2-oxazolin-2-yl Ketone O-methyloxime
[0651] DMF (2.2 ml), potassium carbonate (210 mg, 1.5 mmol) and 2-chloro-5-trifluoromethylpyridine (220 mg, 1.2 mmol) were added to 2-hydroxyphenyl 2-oxazolin-2-yl ketone O-methyloxime (220 mg, 1.0 mmol), and the mixture was stirred at 100° C. for 2.5 hours. After completion of the reaction, 1N NaOH (100 ml) was added, and the mixture was extracted with ether. The ether layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(5-trifluoromethyl-2-pyridyloxy)phenyl 2-oxazolin-2-yl ketone O-methyloxime (190 mg, 52.1%) as an oil.
[0652]
1
H-NMR (CDCl3) δ ppm: 3.78 (2H, t, J=9.8), 3.98 (3H, s), 4.16 (2H, t, J=9.8), 6.94-7.87 (6H, m), 8.43 (1H, brs).
Synthesis of 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile
[0653] Dimethyl sulfoxide (3 ml) and 95% sodium cyanide (0.31 g, 6 mmol) were added to 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminobenzyl chloride (1.03 g, 3 mmol), and the mixture was stirred at 100° C. for 4 hours. After completion of the reaction, ethyl acetate (150 ml) was added, and the mixture was washed with saturated brine (100 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile (0.92 g, 91.5%) as crystals.
[0654]
1
H-NMR (CDCl3) δ ppm: 4.20 (3H, s), 5.15 (2H, s), 6.90-7.41 (6H, m), 7.52 (1H, d, J=2.4).
Synthesis of 5-chloro-2-(4-chlorobenzyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime
[0655] 28% sodium methoxide/methanol solution (1.04 g, 5.4 mmol) was added to a mixture of hydroxylamine hydrochloride (0.38 g, 5.4 mmol) and methanol (6 ml) under ice-cooling over 5 minutes. Then, 5-chloro-2-(4-chlorobenzyloxy)-α-methoxyiminophenylacetonitrile (0.91 g, 2.7 mmol) was added, and the mixture was stirred under reflux for 1.5 hours. After completion of the reaction, water (100 ml) was added, and the mixture was extracted with dichloromethane. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give α-amino-5-chloro-2-(4-chlorobenzyloxy)-α-hydroxyiminoacetophenone O-methyloxime as a crude product.
[0656] Acetic anhydride (2 ml) was added to the crude product, and the mixture was stirred under reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure, ethyl acetate (100 ml) was added, and the mixture was washed with saturated aqueous sodium bicarbonate solution (80 ml) twice. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) and recrystallized from ethyl acetate/n-hexane to give 5-chloro-2-(4-chlorobenzyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.35 g, 33.0%) as colorless crystals.
[0657] mp. 127-128.5° C.
[0658]
1
H-NMR (CDCl3) δ ppm: 2.38 (3H, s), 4.12 (3H, s), 4.85 (2H, s), 6.84-7.61 (7H, m).
Synthesis of 5-chloro-2-hydroxyphenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime
[0659] Aluminium chloride (0.27 g, 2 mmol) was added to a mixture of 5-chloro-2-(4-chlorobenzyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.39 g, 1 mmol) and anisole (3 ml) under ice-cooling, and the mixture was stirred at the same temperature for 1 hour. After completion of the reaction, aqueous sodium bicarbonate solution (100 ml) was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 5-chloro-2-hydroxyphenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.22 g, 82.2%) as colorless crystals. A part of the crystals was recrystallized from ether/n-hexane to give crystals (mp. 92-93.5° C.)
[0660]
1
H-NMR (CDCl3) δ ppm: 2.75 (3H, s), 4.06 (3H, s), 6.82-7.27 (3H, m), 10.22 (1H, s).
Synthesis of 5-chloro-2-(5-trifluoromethyl-2-pyridyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl Ketone O-methyloxime
[0661] Dimethylformamide (1 ml), potassium carbonate (0.10 g, 0.74 mmol) and 5-trifluoromethyl-2-chloropyridine (0.10 g, 0.56 mmol) were added to 5-chloro-2-hydroxyphenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.10 g, 0.37 mmol), and the mixture was stirred at 110° C. for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with saturated brine (80 ml) twice. The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 5-chloro-2-(5-trifluoromethyl-2-pyridyloxy)phenyl 5-methyl-1,2,4-oxadiazol-3-yl ketone O-methyloxime (0.14 g, 91.7%) as a colorless oil.
[0662]
1
H-NMR (CDCl3) δ ppm: 2.46 (3H, s), 4.03 (3H, s), 6.77 (1H, d, J=9.2), 7.16 (1H, d, J=9.2), 7.44-7.86 (3H, m), 8.36 (1H, d, J=1.8).
Synthesis of 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetonitrile
[0663] Dimethyl sulfoxide (2 ml) and 95% sodium cyanide (0.21 g, 0.004 mol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminobenzyl chloride (0.60 g, 0.002 mol), and the mixture was stirred at 110° C. for 2 hours. After completion of the reaction, ether (100 ml) was added, and the mixture was washed with water twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)-αmethoxyiminophenylacetonitrile (0.45 g, 76.4%) as colorless crystals.
[0664]
1
H-NMR (CDCl3) δ ppm: 2.24 (s, 3H), 2.30 (s, 3H) 4.13 (s, 3H), 5.26 (s, 2H), 6.62-7.76 (m, 7H).
Synthesis 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile
[0665] Trifluoroacetic anhydride (3.15 g, 15 mmol) was added to a mixture of 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetamide (1.19 g, 6 mmol) and pyridine (12 ml) under ice-cooling over 20 minutes, and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, ether (150 ml) was added, and the mixture was washed with 1N hydrochloric acid (150 ml), water (100 ml) and saturated aqueous sodium bicarbonate solution (100 ml). The ether layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(4-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (1.57 g, 87.0%) as colorless crystals.
[0666] mp. 69-71° C.
[0667]
1
H-NMR (CDCl3) δ ppm: 4.02 (3H, s), 4.99 (2H, s), 6.86-6.89 (2H, m), 7.23-7.26 (2H, m), 7.36-7.56 (4H, m).
Synthesis of α-methoxyimino-2-methylphenylacetonitrile
[0668] 85% potassium hydroxide (4.0 g, 61 mmol) and 2-methylphenylacetonitrile (6.6 g, 50 mmol) were added to toluene (33 ml), and the mixture was ice-cooled. Methanol (6.6 ml) was added dropwise, and then butyl nitrite (7.0 ml, 60 mmol) was added dropwise while maintaining the temperature of the mixture at 25 to 35° C. The resulting mixture was stirred under ice-cooling for 3 hours. After allowing the mixture to stand at room temperature overnight, water was added to the reaction mixture, and the resulting potassium salt of α-hydroxyimino-2-methylphenylacetonitrile was extracted. Water was added to the extract to a volume of 100 ml. Toluene (50 ml) and tetrabutylammonium bromide (800 mg, 2.5 mmol) were added, and dimethyl sulfate (5.7 ml, 60 mmol) was added under ice-cooling in 4 divided portions. The mixture was stirred at room temperature for additional 30 minutes, and then the organic layer was separated, washed successively with aqueous 1N sodium hydroxide solution and saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give two geometrical isomers A (6.0 g, 69%, as an oil) and B (1.2 g, 14%, as an oil) of α-methoxyimino-2-methylphenylacetonitrile.
[0669] Isomer A: 1H-NMR (CDCl3) δ ppm: 2.51 (3H, s), 4.20 (3H, s), 7.25-7.36 (3H, m), 7.54 (1H, d, J=7.9).
[0670] Isomer B: 1H-NMR (CDCl3) δ ppm: 2.31 (3H, s), 4.06 (3H, s), 7.25-7.39 (4H, m).
Synthesis of 2-bromomethyl-α-methoxyiminophenylacetonitrile
[0671] Benzene (80 ml) was added to α-methoxyimino-2-methylphenylacetonitrile (isomer A) (4.0 g, 23 mmol) and N-bromosuccinimide (4.9 g, 28 mmol), and the mixture was heated under reflux for 1 hour in the presence of azobisisobutyronitrile (190 mg, 1.2 mmol) as a radical initiator. After allowing the mixture to stand for cooling, n-hexane (100 ml) was added, and the mixture was allowed to stand overnight, and the resulting insoluble materials were filtered off. The filtrate was concentrated to dryness under reduced pressure and purified by column chromatography on silica gel (ethyl acetate/n-hexane) to give 2-bromomethyl-α-methoxyiminophenyl-acetonitrile (4.4 g, 76%) as an oil.
[0672]
1
H-NMR (CDCl3) δ ppm: 4.30 (3H, s), 4.79 (2H, s), 7.42-7.50 (3H, m), 7.66-7.69 (1H, m).
Synthesis of 2-(3-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile
[0673] 2-Bromomethyl-α-methoxyiminophenylacetonitrile (5.0 g, 20 mmol) and 3-chlorophenol (3.0 g, 23 mmol) were dissolved in dimethylformamide (25 ml), and the mixture was stirred at room temperature for 2 hours in the presence of potassium carbonate (3.3 g, 24 mmol). After completion of the reaction, diethyl ether (ca. 100 ml) was added to the reaction mixture, and the mixture was washed successively with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane) and crystallized from diethyl ether/n-hexane to give 2-(3-chlorophenoxymethyl)-α-methoxyiminophenylacetonitrile (3.7 g, 62%) as colorless crystals.
[0674] mp. 62-63° C.
[0675]
1
H-NMR (CDCl3) δ ppm: 4.11 (3H, s), 5.25 (2H, s), 6.82 (1H, d, J=8.3), 6.95-6.97 (2H, m), 7.21 (1H, t, J=8.3), 7.45-7.53 (2H, m), 7.67 (1H, d, J=7.3), 7.75 (1H, dd, J=7.3, 1.5).
Synthesis of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene
[0676] Pyridinium p-toluenesulfonate (0.30 g, 0.0012 mol) was added to a solution of 2-bromobenzylalcohol (25 g, 0.134 mol) in dichloromethane (100 ml), and the mixture was stirred at room temperature. 3,4-Dihydro-2H-pyran (16.86 g, 0.20 mol) was added thereto. The mixture was stirred at room temperature for 2 hours. Then, saturated aqueous sodium bicarbonate solution (200 ml) was added, and the mixture was extracted with dichloromethane (200 ml). After drying over anhydrous magnesium sulfate, the solvent was evaporated to give the desired 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (36.00 g, yield: 99.3%) as an oil.
[0677]
1
H-NMR (CDCl3) δ ppm: 1.45-1.80 (6H, m), 3.45-3.55 (1H, m), 3.80-3.90 (1H, m), 4.52 (1H, d, J=15.0), 4.80 (1H, m), 4.90 (1H, d, J=15.0), 7.16 (1H, t, J=7.3), 7.31 (1H, t, J=7.3), 7.51 (1H, d, J=7.3), 7.54 (1H, d, J=7.3).
Synthesis of 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl Ketone
[0678] Magnesium (0.73 g, 0.03 mol) and bromoethane (0.2 ml) were added to a mixture of 1-bromo-2-(2-tetrahydropyranyloxymethyl)benzene (5.42 g, 0.02 mol) and THF (50 ml) under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 60° C. for 1 hour to prepare Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-3, N-dimethyl-5-isoxazolcarboxamide (3.40 g, 0.02 mol) and THF (40 ml). The mixture was stirred at −60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, yield: 67.9%) as a colorless oil.
[0679]
1
H-NMR (CDCl3) δ ppm: 1.41-1.74 (6H, m), 2.39 (3H, s), 3.45-3.51 (1H, m), 3.75-3.83 (1H, m), 4.59-4.60 (1H, m), 4.71 (1H, d, J=12.8), 4.94 (1H, d, J=12.8), 6.69 (1H, s), 7.38-7.63 (4H, m).
Synthesis of 2-hydroxymethylphenyl 3-methylisoxazol-5-yl Ketone O-methyloxime
[0680] Methanol (25 ml), methoxyamine hydrochloride (2.17 g, 0.026 mol) and pyridine (2.1 ml, 0.026 mol) were added to 2-(2-tetrahydropyranyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone (4.09 g, 0.013 mol), and the mixture was stirred under reflux for 3 hours. After completion of the reaction, half-saturated brine (200 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.63 g, yield: 19.7%, as a colorless oil) and isomer B (1.62 g, yield: 50.7%, as a colorless oil) of 2-hydroxymethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime.
[0681] Isomer A: 1H-NMR (CDCl3) δ ppm: 2.39 (3H, s), 2.74 (1H, t, J=6.7), 4.17 (3H, s), 4.54 (2H, d, J=6.7), 7.02 (1H, s), 7.33-7.55 (4H, m)
[0682] Isomer B: 1H-NMR (CDCl3) δ ppm: 1.89 (1H, t, J=6.1), 2.28 (3H, s), 4.03 (3H, s), 4.52 (2H, d, J=6.1), 6.05 (1H, s), 7.17-7.62 (4H, m).
Synthesis of 2-(3-chloro-5-trifluoromethyl-2-pyridyloxymethyl)phenyl 3-methylisoxazol-5-yl Ketone O-methyloxime
[0683] THF (7.5 ml), 2,3-dichloro-5-trifluoromethylpyridine (0.81 g, 3.75 mmol) and 60% sodium hydride (0.12 g, 3.0 mmol) were added to 2-hydroxymethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.62 g, 2.5 mmol) under ice-cooling, and the mixture was stirred at room temperature overnight. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ether (150 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give isomer A (0.29 g, yield: 27.2%) and isomer B (0.76 g, yield: 71.4%) of 2-(3-chloro-5-trifluoromethyl-2-pyridyloxymethyl)phenyl 3-methylisoxazol-5-yl ketone O-methyloxime.
[0684] Isomer A: mp. 77-79° C., 1H-NMR (CDCl3) δ ppm: 2.37 (3H, s), 4.14 (3H, s), 5.45 (2H, s), 6.97 (1H, s), 7.36-7.63 (4H, m), 7.79 (1H, d, J=2.4), 8.09 (1H, d, J=2.4).
[0685] Isomer B: 1H-NMR (CDCl3) δ ppm: 2.28 (3H, s), 4.04 (3H, s), 5.33 (2H, s), 6.01 (1H, s), 7.20-7.65 (4H, m), 7.80 (1H, d, J=2.2), 8.08 (1H, d, J=2.2).
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl thiazolidin-2-yl Ketone O-methyloxime
[0686] Toluene (3 ml), butanol (3 ml), cysteamine hydrochloride (0.34 g, 3.0 mmol) and triethylamine (0.42 ml, 3 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetoaldehyde (0.45 g, 1.5 mmol), and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, half-saturated brine (100 ml) was added, and the mixture was extracted with dichloromethane (50 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl thiazolidin-2-yl ketone O-methyloxime (0.49 g, yield 91.6%) as a colorless oil.
[0687]
1
H-NMR (CDCl3) δ ppm: 2.28 (6H, s), 2.40 (1H, brs), 2.81-3.06 (3H, m), 3.38-3.55 (1H, m), 3.87 (3H, s), 4.85-5.50 (3H, m), 6.67-7.64 (7H, m)
Synthesis of 2-(2,5-dimethylphenoxymethyl)phenyl 1,3-dioxolan-2-yl Ketone O-methyloxime
[0688] Benzene (4 ml), ethylene glycol (0.12 g, 2.0 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.05 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde (0.3 g, 1.0 mmol), and the mixture was subjected to azeotropic dehydration for 2 hours. After completion of the reaction, half-saturated brine (100 ml) was added, and the mixture was extracted with dichloromethane (50 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl 1,3-dioxolan-2-yl ketone O-methyloxime (0.30 g, yield 87.9%) as colorless crystals. mp 136-137° C.
[0689]
1
H-NMR (CDCl3) δ ppm: 2.28 (3H, m), 2.29 (3H, s), 3.59-3.85 (4H, m), 3.92 (3H, s), 5.04 (1H, s), 5.09 (1H, s), 5.63 (1H, s), 6.66-7.62 (7H, m).
Synthesis of 1-bromo-2-(1-ethoxyethyl)oxymethylbenzene
[0690] Pyridinium p-toluenesulfonate (0.50 g, 0.002 mol) was added to a mixture of 2-bromobenzylalcohol (18.70 g, 0.1 mol), dichloromethane (150 ml) and ethyl vinyl ether (14.42 g, 0.2 mol) under ice-cooling, and the mixture was stirred at room temperature for 3 hours. After completion of the reaction, half-saturated aqueous sodium bicarbonate solution (300 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 1-bromo-2-(1-ethoxyethyl)oxymethylbenzene (25.44 g, yield: 98.2%) as a colorless oil.
[0691]
1
H-NMR (CDCl3) δ ppm: 1.22 (3H, t, J=7.3), 1.41 (3H, t, J=5.5), 3.49-3.77 (2H, m), 4.59 (1H, d, J=12.8), 4.70 (1H, d, J=12.8), 4.87 (1H, q, J=5.5), 7.11-7.55 (4H, m).
Synthesis of 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl Ketone
[0692] A mixture of 1-bromo-2-(1-ethoxyethyl)oxymethylbenzene (12.96 g, 0.05 mol) and THF (45 ml) was added to a mixture of magnesium (1.82 g, 0.075 mol) and bromoethane (0.2 ml) and THF (5 ml) at 45 to 55° C. under an atmosphere of nitrogen gas, and the resulting mixture was stirred at 50 to 55° C. for 1 hour to prepare a Grignard reagent. The Grignard reagent was added dropwise to a mixture of N-methoxy-5, N-dimethyl-3-isoxazolcarboxamide (5.62 g, 0.033 mol) and THF (40 ml) cooled to −50° C. The mixture was stirred at −60° C. to room temperature for 1 hour, water (200 ml) was added, and the mixture was extracted with ether (200 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetatein-hexane) to give 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone (8.61 g, yield: 90.2%) as a colorless oil.
[0693]
1
H-NMR (CDCl3) δ ppm: 1.16 (3H, t, J=6.7), 1.27 (3H, d, J=5.5), 2.52 (3H, s), 3.43-3.65 (2H, m), 4.68-4.92 (3H, m), 6.50 (1H, s), 7.36-7.84 (4H, m).
Synthesis of 2-(l-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl Ketone O-methyloxime
[0694] 2-(1-Ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone (4.34 g, 0.015 mol) was added to a mixture of methanol (30 ml), methoxyamine hydrochloride (2.51 g, 0.03 mol) and 28% sodium methylate/methanol solution (7.23 g, 0.0375 mol), and the mixture was stirred under reflux for 3 hours. After completion of the reaction, half-saturated brine (200 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (4.32 g, yield: 90.5%) as a colorless oil.
[0695]
1
H-NMR (CDCl3) δ ppm: 1.11-1.26 (6H, m), 2.47 (2.43) (3H, s), 3.39-3.60 (2H, m), 4.08 (3.97) (3H, s), 4.11-4.70 (3H, m), 6.61 (6.37) (1H, s), 7.19-7.56 (4H, m).
Synthesis of 2-hydroxymethylphenyl 5-methylisoxazol-3-yl Ketone O-methyloxime
[0696] Methanol (26 ml) and pyridinium p-toluenesulfonate (0.33 g, 0.0013 mol) were added to 2-(1-ethoxyethyl)oxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (4.14 g, 0.013 mol), and the mixture was stirred under reflux for 0.5 hour. After completion of the reaction, half-saturated brine (300 ml) was added, and the mixture was extracted with dichloromethane (100 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-hydroxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (2.95 g, yield: 92.1%) as a colorless oil.
[0697]
1
H-NMR (CDCl3) δ ppm: 2.43 (3.18) (1H, t, J=6.7), 2.44 (2.50) (3H, s), 3.99 (4.11) (3H, s), 4.47 (4.57) (2H, d, J=6.7), 6.44 (6.62) (1H, s), 7.19-7.60 (4H, m).
Synthesis of 2-(5-chloro-3-trifluoromethyl-2-pyridyloxymethyl)phenyl 5-methylisoxazol-3-yl Ketone O-methyloxime
[0698] THF (3 ml), 2,5-dichloro-3-trifluoromethylpyridine (0.32 g, 1.5 mmol) and 60% sodium hydride (0.05 g, 1.2 mmol) were added to 2-hydroxymethylphenyl 5-methylisoxazol-3-yl ketone O-methyloxime (0.25 g, 1.0 mmol) under ice-cooling, and the mixture was stirred at room temperature overnight. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ether (150 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(5-chloro-3-trifluoromethyl-2-pyridyloxymethyl)phenyl 5-methylisoxazol-3-yl ketone O-methyloxime (0.41 g, yield: 96.3%) as colorless crystals.
[0699] mp. 120-121° C. (ether/n-hexane)
[0700]
1
H-NMR (CDCl3) δ ppm: 2.45 (3H, s), 3.99 (3H, s) , 5.34 (2H, s), 6.39 (1H, s), 7.23-7.64 (2H, m), 7.79 (1H, d, J=2.5), 8.06 (1H, d, J=2.5).
Synthesis of 2-chloromethylphenyl 3-methylisoxazol-5-yl Ketone O-methyloxime
[0701] Benzene (5 ml) and thionyl chloride (0.36 g, 3.0 mmol) were added to 2-hydroxymethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.62 g, 2.5 mmol), and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-chloromethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.26 g, yield: 39.3%) as a colorless oil.
[0702]
1
H-NMR (CDCl3) δ ppm: 2.29 (3H, s), 4.04 (3H, s), 4.47 (2H, s), 6.05 (1H, s), 7.18-7.60 (4H, m).
Synthesis of 2-(3,4-dichloro-α-methylbenzylideneaminooxymethyl)phenyl 3-methylisoxazol-5-yl Ketone O-methyloxime
[0703] DMF (3 ml), 3,4-dichloroacetophenone oxime (0.31 g, 1.5 mmol) and potassium carbonate (0.28 g, 2.0 mmol) were added to 2-chloromethylphenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.26 g, 1.0 mmol), and the mixture was stirred at 60° C. for 2 hours. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ether (150 ml). The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-(3,4-dichloro-α-methylbenzylideneaminooxymethyl)phenyl 3-methylisoxazol-5-yl ketone O-methyloxime (0.37 g, yield: 85.6%) as colorless crystals.
[0704]
1
H-NMR (CDCl3) δ ppm: 2.01 (3H, s), 2.21 (3H, s), 4.04 (3H, s), 5.13 (2H, s), 5.96 (1H, s), 7.20-7.64 (7H, m). mp. 84-85° C.
Synthesis of 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetaldehyde
[0705] 1M diisobutylaluminum hydride/toluene solution (11 ml, 16.5 mmol) was added dropwise to a mixture of methyl 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetate (4.83 g, 11.8 mmol) and dichloromethane (47 ml) at −65° C. or lower over 4 minutes, and the mixture was stirred at −78° C. to room temperature for 3 hours. Methanol (7 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The precipitated insoluble materials were removed, and the remaining mixture was concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetaldehyde (2.11 g, 47.3%) as a colorless oil.
[0706]
1
H-NMR (CDCl3) δ ppm: 2.19 (3H, s), 4.11 (3H, s), 5.09 (2H, s), 7.09-7.12 (1H, m), 7.36-7.52 (4H, m), 7.59 (1H, d, J=7.9), 7.77 (1H, d, J=7.9), 7.85 (1H, s), 9.70 (1H, s).
Synthesis of 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]phenyl Thiazolidin-2-yl Ketone O-methyloxime
[0707] Toluene (2.5 ml), butanol (2.5 ml), cysteamine hydrochloride (0.29 g, 2.54 mmol) and triethylamine (0.26 g, 2.54 mmol) were added to 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]-α-methoxyiminophenylacetaldehyde (0.48 g, 1.27 mmol), and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, half-saturated brine (100 ml) was added, and the mixture was extracted with dichloromethane (50 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/n-hexane) to give 2-[(α-methyl-3-trifluoromethylbenzylidene)aminooxy]phenyl thiazolidin-2-yl ketone O-methyloxime (0.52 g, yield 93.6%) as a colorless oil.
[0708]
1
H-NMR (CDCl3) δ ppm: 2.39 (3H, s), 2.75-3.10 (3H, m), 3.50 (2H, m), 3.86 (3H, s), 5.20-5.30 (2H, m), 5.45 (1H, m), 7.37-7.61 (6H, m), 7.82 (1H, d, J=7.9), 7.91 (1H, s).
[0709] According to the same manner as that in Examples 24 and 30, various compounds of the formula (XLVIII), which are intermediates for production of the compound (I), were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds (XLVIII-7) and (XLVIII-4) obtained in Examples 24 and 30, respectively, are also listed.
3|
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NoR3R4PPhysical data
|
XLVIII-1Isoxazol-3-ylHTetrahydropyranyl
XLVIII-2Isoxazol-3-ylH1-C2H5OC2H41H-NMR(CDCl3)δppm :1.16(3H, t,
J=7.3), 1.26(3H, d, J=5.5), 3.40-
3.65(2H, m), 4.70-4.93(3H, m),
6.89(1H, d, J=1.8), 7.37-7.87(4H,
m), 8.53(1H, J=1.8)
XLVIII-35-Me-HTetrahydropyranyl
Isoxazol-3-yl
XLVIII-45-Me-H1-C2H5OC2H41H-NMR(CDCl3)δppm: 1.16(3H, t,
isoxazol-3-ylJ=6.7), 1.27(3H, d, J=5.5), 2.52(3H,
s), 3.43-3.65(2H, m), 4.68-4.92(3H,
m), 6.50(1H, s), 7.36-7.84(4H, m).
XLVIII-5Isoxazol-5-ylHTetrahydropyranyl
XLVIII-6Isoxazol-5-ylH1-C2H5OC2H4
XLVIII-73-Me-HTetrahydropyranyl1H-NMR(CDCl3)δppm: 1.41-1.74
soxazol-5-yl(6H, m), 2.39(3H, s), 3.45-3.51(1H,
m), 3.75-3.83(1 H, m), 4.59-4.60
(1H, m), 4.71(1H, d, J=12.8), 4.94
(1H, d, J=12.8), 6.69(1H, s), 7.38-
7.63(4H, m).
XLVIII-83-Me-H1-C2H5OC2H41H-NMR(CDCl3)δppm: 1.16(3H, t,
isoxazol-5-ylJ=7.3), 1.25(3H, d, J=5.5), 2.40(3H,
s), 3.42-3.61(2H, m), 4.68-4.88(3H,
m), 6.70(1H, s), 7.37-7.66(4H, m)
XLVIII-91,3,4-HTetrahydropyranyl
Oxadiazol-2-yl
XLVIII-101,3,4-
Oxadiazol-2-ylH1-C2H5OC2H4
XLVIII-111-Me-imidazol-HTetrahydropyranyl
2-yl
XLVIII-121-Me-imidazol-H1-C2H5OC2H4
2-yl
XLVIII-132-Isoxazolin-3-HTetrahydropyranyl
yl
XLVIII-142-Isoxazolin-3-H1-C2H5OC2H4
yl
XLVIII-155-Me-2-HTetrahydropyranyl
isoxazolin-3-yl
XLVIII-165-Me-2-H1-C2H5OC2H4
isoxazolin-3-yl
XLVIII-172-FurylHTetrahydropyranyl
XLVIII-182-FurylH1-C2H5OC2H4
XLVIII-195-Me-1,2,4-HTetrahydropyranyl
oxadiazol-3-yl
XLVIII-205-Me-1,2,4-H1-C2H5OC2H4
oxadiazol-3-yl
|
[0710] According to the same manner as that in Examples described above, various compounds of the formula (I) were synthesized. The compounds thus obtained and their physical data are as follows. In the following tables, the physical data of the compounds obtained in the above Examples are also listed. “No.” represents a compound number. When the product is obtained as a mixture of isomers A/B, the δ values of either isomer are indicated in the parentheses.
[0711] The basic structures of the compound (I) in the tables are as follows:
4|
|
|
596061
|
NoR1R2R3nPhysical data
|
1C6H5MeImidazol-1-yl1mp 66-67.5° C.
22-F—C6H4MeImidazol-1-yl1
33-F—C6H4MeImidazol-1-yl1
44-F—C6H4MeImidazol-1-yl1
52-Cl—C6H4MeImidazol-1-yl1mp 79.5--80.5° C.
63-Cl—C6H4MeImidazol-1-yl1mp 96.5-97.5° C.
74-Cl—C6H4MeImidazol-1-yl1mp 88-88.5° C.
82-Br—C6H4MeImidazol-1-yl1
93-Br—C6H4MeImidazol-1-yl1
104-Br—C6H4MeImidazol-1-yl1
113-I—C6H4MeImidazol-1-yl1
124-I—C6H4MeImidazol-1-yl1
132-Me—C6H4MeImidazol-1-yl11H-NMR(CDCl3) δ ppm:
2.16(3H, s), 3.99(3H, s),
4.98(2H, s), 6.68-7.66(10H,
m), 7.96(1H, s)
143-Me—C6H4MeImidazol-1-yl1
154-Me—C6H4MeImidazol-1-yl1mp 58-65° C.
162-Et—C6H4MeImidazol-1-yl11H-NMR(CDCl3) δ ppm:
1.16(3H, t, J=7.3), 2.60(2H, q,
J=7.3), 3.99(3H, s), 4.98(2H,
s), 6.69-7.67(10H, m),
7.96(1H, s)
173-Et—C6H4MeImidazol-1-yl1
184-Et—C6H4MeImidazol-1-yl1
192-MeO—C6H4MeImidazol-1-yl1
203-MeO—C6H4MeImidazol-1-yl1
214-MeO—C6H4MeImidazol-1-yl1
222-CF3—C6H4MeImidazol-1-yl1
233-CF3—C6H4MeImidazol-1-yl1
244-CF3—C6H4MeImidazol-1-yl1
252,3-F2—C6H3MeImidazol-1-yl1
262,4-F2—C6H3MeImidazol-1-yl1
272,5-F2—C6H3MeImidazol-1-yl1
282,6-F2—C6H3MeImidazol-1-yl1
293,4-F2—C6H3MeImidazol-1-yl1
303,5-F2—C6H3MeImidazol-1-yl1
312,3-Cl2—C6H3MeImidazol-1-yl1
322,4-Cl2—C6H3MeImidazol-1-yl1
332,5-Cl2—C6H3MeImidazol-1-yl1
342,6-Cl2—C6H3MeImidazol-1-yl1
353,4-Cl2—C6H3MeImidazol-1-yl1
363,5-Cl2—C6H3MeImidazol-1-yl1
372,3-Me2C6H3MeImidazol-1-yl1
382,4-Me2—C6H3MeImidazol-1-yl1
392,5-Me2—C6H3MeImidazol-1-yl11H-NMR(CDCl3) δ ppm:
2.11(3H, s), 2.26(3H, s),
3.99(3H, s), 4.96(2H, s),
6.52(1H, s), 6.66(1H, d,
J=7.3), 6.98-7.66(7H, m),
7.96(1H, s)
402,6-Me2—C6H3MeImidazol-1-yl11H-NMR(CDCl3) δ ppm:
2.17(6H, s), 4.01 (3H, s),
4.78(2H, s), 6.89—7.85(9H, m),
8.04(1H, s)
413,4-Me2—C6H3MeImidazol-1-yl1
423,5-Me2—C6H3MeImidazol-1-yl1
432-Cl-4-Me—C6H3MeImidazol-1-yl1
442-Cl-5-Me—C6H3MeImidazol-1-yl1
454-Cl-2-Me—C6H3MeImidazol-1-yl1
464-Cl-3-Me—C6H3MeImidazol-1-yl1
472,3,5-Me3—C6H2MeImidazol-1-yl1
483-Ph—C6H4MeImidazol-1-yl1
494-Ph—C6H4MeImidazol-1-yl1
502-i-Pr—C6H4MeImidazol-1-yl1
513-i-Pr—C6H4MeImidazol-1-yl1
524-i-Pr—C6H4MeImidazol-1-yl1
533-t-Bu—C6H4MeImidazol-1-yl1
544-t-Bu—C6H4MeImidazol-1-yl1
553-i-PrO—C6H4MeImidazol-1-yl1
564-i-PrO—C6H4MeImidazol-1-yl1
572-Cl-MeImidazol-1-yl1mp 107.5-108.5° C.
pyridin-3-yl
584-MeS—C6H4MeImidazol-1-yl1
59Pyridin-3-ylMeImidazol-1-yl1
602,4,5-Cl3—C6H2MeImidazol-1-yl1
61C6H5EtImidazol-1-yl11H-NMR(CDCl3) δ ppm:
1.30(3H, t, J=6.7), 4.21(2H, q,
J=6.7), 5.02(2H, s), 6.78-
7.64(11H, m), 8.04(1H, s)
622-F—C6H4EtImidazol-1-yl1
633-F—C6H4EtImidazol-1-yl1
644-F—C6H4EtImidazol-1-yl1
652-Cl—C6H4EtImidazol-1-yl1
663-Cl—C6H4EtImidazol-1-yl1
674-Cl—C6H4EtImidazol-1-yl1
682-Br—C6H4EtImidazol-1-yl1
693-Br—C6H4EtImidazol-1-yl1
704-Br—C6H4EtImidazol-1-yl1
713-I—C6H4EtImidazol-1-yl1
722-Me—C6H4EtImidazol-1-yl1
733-Me—C6H4EtImidazol-1-yl1
744-Me—C6H4EtImidazol-1-yl1
752-Et—C6H4EtImidazol-1-yl1
763-Et—C6H4EtImidazol-1-yl1
774-Et—C6H4EtImidazol-1-yl1
782-MeO—C6H4EtImidazol-1-yl1
793-MeO—C6H4EtImidazol-1-yl1
804-MeO—C6H4EtImidazol-1-yl1
81C6H5AllylImidazol-1-yl11H-NMR(CDCl3) δ ppm: 4.63-
4.66(2H, m), 5.02(2H, s), 5.20-
5.33(2H, m), 5.86-6.01 (1H, m),
6.77-7.64(11H, m), 8.03(1H, s)
822-F—C6H4AllylImidazol-1-yl1
833-F—C6H4AllylImidazol-1-yl1
844-F—C6H4AllylImidazol-1-yl1
852-Cl—C6H4AllylImidazol-1-yl1
863-Cl—C6H4AllylImidazol-1-yl1
874-Cl—C6H4AllylImidazol-1-yl1
882-Br—C6H4AllylImidazol-1-yl1
893-Br—C6H4AllylImidazol-1-yl1
904-Br—C6H4AllylImidazol-1-yl1
913-I—C6H4AllylImidazol-1-yl1
922-Me—C6H4AllylImidazol-1-yl1
933-Me—C6H4AllylImidazol-1-yl1
944-Me—C6H4AllylImidazol-1-yl1
952-Et—C6H4AllylImidazol-1-yl1
963-Et—C6H4AllylImidazol-1-yl1
974-Et—C6H4AllylImidazol-1-yl1
982-MeO—C6H4AllylImidazol-1-yl1
993-MeO—C6H4AllylImidazol-1-yl1
1004-MeO—C6H4AllylImidazol-1-yl1
101C6H5Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.85(3H, s), 3.95(3H, s),
4.93(2H, s), 6.80-7.57(11H, m)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 3.51(3H, s), 3.99(3H, s),
4.91(2H, s), 6.83-7.57(11H, m)
1022-F—C6H4Me1-Me-1
imidazol-2-yl
1033-F—C6H4Me1-Me-1
imidazol-2-yl
1044-F—C6H4Me1-Me-1Isomer A: mp 99.5-100.5° C.
imidazol-2-ylIsomer B: mp 114.5-115.5 C.
1052-Cl—C6H4Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.91 (3H, s), 3.96(3H, s),
5.04(2H, s), 6.81-7.65(10H, m)
Isomer B: mp 146.5-147.5° C.
1063-Cl—C6H4Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.88(3H, s), 3.96(3H, s),
4.94(2H, s), 6.69-7.54(10H, m)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 3.53(3H, s), 4.00(3H, s),
4.94(2H. s), 6.74-7.55(10H, m)
1074-Cl—C6H4Me1-Me-1Isomer A: mp 122.0-123.0° C.
imidazol-2-ylIsomer B: mp 144.5-145.5° C.
1082-Br—C6H4Me1-Me-1
imidazol-2-yl
1093-Br—C6H4Me1-Me-1
imadazol-2-yl
1104-Br—C6H4Me1-Me-1
imidazol-2-yl
1113-I—C6H4Me1-Me-1
imidazol-2-yl
1122-Me—C6H4Me1-Me-1Isomer A: 1H-NMR(CDCL3) δ
imidazol-2-ylppm: 2.18(3H, s), 3.85(3H, s),
3.96(3H, s), 4.93(2H, s), 6.73-
7.60(10H, m)
Isomer B: mp 126.0-127.0° C.
1133-Me—C6H4Me1-Me-1Isomer A: mp 88.0-91.0° C.
imidazol-2-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.31 (3H, s), 3.51(3H, s),
4.01(3H, s), 4.89(2H, s), 6.63-
7.65(10H, m)
1144-Me—C6H4Me1-Me-1Isomer A: mp 105.5-106.5° C.
imidazol-2-ylIsomer B: mp 118.5-119.5° C.
1152-Et—C6H4Me1-Me-1
imidazol-2-yl
1163-Et—C6H4Me1-Me-1
imidazol-2-yl
1174-Et—C6H4Me1-Me-1
imidazol-2-yl
1182-MeO—C6H4Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.85(3H, s), 3.91(3H, s),
3.96(3H, s),
5.04(2H, s), 6.74-7.65(10H, m)
Isomer B: mp 108.5-109.5° C.
1193-MeO—C6H4Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.74(3H, s), 3.85(3H, s),
3.95(3H, s), 4.91(2H, s),
6.38-7.56(10H, m)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 3.52(3H, s), 3.77(3H, s),
4.00(3H, s), 4.89(2H, s), 6.44-
7.56(10H, m)
1204-MeO—C6H4Me1-Me-1
imidazol-2-yl
1212-CF3—C6H4Me1-Me-1
imidazol-2-yl
1223-CF3—C6H4Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.86(3H, s), 3.95(3H, s),
4.99(2H, s), 6.92-7.54(10H, m)
Isomer B: mp 106.0-107.0° C.
1234-CF3—C6H4Me1-Me-1
imidazol-2-yl
1242,4-F2—C6H3Me1-Me-1
imidazol-2-yl
1252,5-F2—C6H3Me1-Me-1
imidazol-2-yl
1262,6-F2—C6H3Me1-Me-1
imidazol-2-yl
1273,4-F2—C6H3Me1-Me-1
imidazol-2-yl
1283,5-F2—C6H3Me1-Me-1
imidazol-2-yl
1292,3-Cl2—C6H3Me1-Me-1
imidazol-2-yl
1302,4-Cl2—C6H3Me1-Me-1Isomer A: mp 115.0-116.0° C.
imidazol-2-ylIsomer B: mp 157.5-158.5° C.
1312,5-Cl2—C6H3Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.94(3H, s), 3.98(3H, s),
5.04(2H, s), 6.82-7.65(9H, m)
Isomer B: mp 128.5-130.0° C.
|
1323,4-Cl2—C6H3Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.91(3H, s), 3.96(3H, s),
4.94(2H, s), 6.67-7.65(9H, m)
Isomer B: mp 124.5-125.5° C.
1333,4-Cl2—C6H3Me1-Me-1
imidazol-2-yl
1342,3-Me2—C6H3Me1-Me-1
imidazol-2-yl
1352,4-Me2—C6H3Me1-Me-1
imidazol-2-yl
1362,5-Me2—C6H3Me1-Me-1Isomer A1H-NMR(CDCl3) δ
imidazol-2-ylppm: 2.13(3H, s), 2.24(3H, s),
3.86(3H, s), 3.97(3H, s),
4.92(2H, s), 6.55(1H, s),
6.63(1H, d, J=7.9), 6.91(1H,
s), 6.98(1H, d, J=7.9),
7.26(1H, s), 7.29-7.60(4H, m)
Isomer B1H-NMR(CDCl3) δ
ppm: 2.21(3H, s), 2.29(3H, s),
3.49(3H, s), 4.03(3H, s),
4.92(2H, s), 6.53(1 H, s),
6.67(1H, d, J=7.3), 6.95(1H, d,
J=1.2), 7.01(1H, d, 7.3),
7.17(1H, d, J=1.2), 7.30-
7.65(4H, m)
1373,4-Me2—C6H3Me1-Me-1
imidazol-2-yl
1383,5-Me2—C6H3Me1-Me-1
imidazol-2-yl
1392-Cl-4-Me—C6H3Me1-Me-1
imidazol-2-yl
1402-Cl-5-Me—C6H3Me1-Me-1
imidazol-2-yl1
1414-Cl-2-Me—C6H3Me1-Me-1Isomer A: mp 87.0-88.0° C.
imidazol-2-ylIsomer B: mp 134.0-135.0° C.
1424-Cl-3-Me—C6H3Me1-Me-1
imidazol-2-yl
1433-Ph—C6H4Me1-Me-1
imidazol-2-yl
1444-Ph—C6H4Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 3.87(3H, s), 3.97(3H,
s), 4.98(2H, s), 6.88-7.64(15H, m)
Isomer B: mpl4l.5-142.5t
1453-i-PrO—C6H4Me1-Me-1
imidazol-2-yl
1463-i-Pr-C6H4Me1-Me-1Isomer A: 1H-NMR(CDCl3) δ
imidazol-2-ylppm: 1.20(6H, d, J=7.3),
2.83(1H, sept, J=7.3),
3.82(3H, s), 3.96(3H, s),
4.91(2H, s), 6.61-7.57(10H, m)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 1.23(6H, d, J=7.3),
2.86(1H, sept, J=7.3),
3.50(3H, s), 4.00(3H, s),
4.88(2H, s), 6.64-7.58(10H, m)
1474-i-Pr—C6H4Me1-Me-1
imidazol-2-yl
1483-t-Bu—C6H4Me1-Me-1
imidazol-2-yl
1492-MeS—C6H4Me1-Me-1
imidazol-2-yl1
1504-MeS—C6H4Me1-Me-1
imidazol-2-yl
|
1512,3,6-F3C6H2Me1-Me-1
imidazol-2-yl
1522,4,5-CL3—C6H2Me1-Me-1
imidazol-2-yl
1533-PhO—C6H4Me1-Me-1
imidazol-2-yl
1543,4,5-(MeO)3—C6H2Me1-Me-1
imidazol-2-yl
1552,3,5-Me3—C6H2Me1-Me-1
imidazol-2-yl
1563,4,5-Me3—C6H2Me1-Me-1
imidazol-2-yl
157C6F5Me1-Me-1
imidazol-2-yl
1584-Cl-3-Et—C6H3Me1-Me-1
imidazol-2-yl
1593-EtO—C6H4Me1-Me-1
imidazol-2-yl
1604-EtO—C6H4Me1-Me-1
imidazol-2-yl
|
161C6H5Me1-Me-01H-NMR(CDCl3) δ ppm:
imiazol-2-yl3.48(3H, s), 4.02(3H, s), 6.67-
7.36(10H, m), 7.75(1H, dd,
J=7.3, 1.8)
1624-F—C6H4Me1-Me-0
imidazol-2-yl
1633-Cl—C6H4Me1-Me-0
imidazol-2-yl
1644-Cl—C6H4Me1-Me-0
imidazol-2-yl
1653-Me—C6H4Me1-Me-0
imidazol-2-yl
1664-Me—C6H4Me1-Me-0
imidazol-2-yl
1674-Et—C6H4Me1-Me-0
imidazol-2-yl
1684-NO2—C6H4Me1-Me-0
imidazol-2-yl
1693,4-Cl2—C6H3Me1-Me-0
imidazol-2-yl
1703,5-Cl2—C6H3Me1-Me-0
imidazol-2-yl
1713,4-Me2—C6H3Me1-Me-0
imidazol-2-yl
1723,5-Me2—C6H3Me1-Me-0
imidazol-2-yl
1733-PhO—C6H4Me1-Me-0
imidazol-2-yl
1744-Cl-3-Et—C6H3Me1-Me-0
imidazol-2-yl
1753-EtO—C6H4Me1-Me-0
imidazol-2-yl
1763-CF3C6H4Me1-Me-0
imidazol-2-yl
1774-CF3—C6H4Me1-Me-0
imidazol-2-yl
1783-i-PrO—C6H4Me1-Me-0
imidazol-2-yl
1793-i-Pr—C6H4Me1-Me-0
imidazol-2-yl
1804-Cl-3-Me—C6H3Me1-Me-0
imidazol-2-yl
181Pyridin-2-ylMe1-Me-1
imidazol-2-yl
182Pyridin-3-ylMe1-Me-1
imidazol-2-yl
1835-Cl-Me1-Me-1
pyridin-2-ylimidazol-2-yl
1843-Cl-Me1-Me-1
pyridin-2-ylimidazol-2-yl
1856-Cl-Me1-Me-1
pyridin-2-ylimidazol-2-yl
1862-Cl-Me1-Me-1
pyridin-3-ylimidazol-2-yl
1875-CF3-Me1-Me-1
pyridin-2-ylimidazol-2-yl
1883-CF3-Me1-Me-1
pyridin-2-ylimidazol-2-yl
1896-CF3-3-Cl-Me1-Me-1
pyridin-2-ylimidazol-2-yl
1905-CF3-3-Cl-Me1-Me-1
pyridin-2-ylimidazol-2-yl
191Benzothiazol-Me1-Me-1
2-ylimidazol-2-yl
192Benzoxazol-Me1-Me-1
2-ylimidazol-2-yl
193Quinolin-2-ylMe1-Me-1
imidazol-2-yl
1945-CF3-1,3,4-Me1-Me-1
thiadiazol-2-ylimidazol-2-yl
195Pyrimidin-2-ylMe1-Me-1
imidazol-2-yl
1965-Cl-6-Me-Me1-Me-1
pyrimidin-4-ylimidazol-2-yl
1975-Et-6-Me-Me1-Me-1
pyrimidin-4-ylimidazol-2-yl
1986-Cl-Me1-Me-1
pyrazin-2-ylimidazol-2-yl
1993,6-Me2-Me1-Me-1
pyrazin-2-ylimidazol-2-yl
2005-Me-Me1-Me-1
isoxazol-3-ylimidazol-2-yl
201C6H5Me5-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl1.95(3H, s), 3.92(3H, s),
5.18(2H, s), 6.86-7.71(11H, m)
2022-F—C6H4Me5-Me-1
imidazol-1-yl
2033-F—C6H4Me5-Me-1
imidazol-1-yl
2044-F—C6H4Me5-Me-1
imidazol-1-yl
2052-Cl—C6H4Me5-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl1.94(3H, d, J=1.2), 3.96(3H,
s), 5.24(2H, s), 6.86-7.82(10H, m)
2063-Cl—C6H4Me5-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl1.96(3H, s), 3.93(3H, s),
5.18(2H, s), 6.79-7.67(10H, m)
2074-Cl—C6H4Me5-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl1.94(3H, s), 3.92(3H, s),
5.13(2H, s), 6.82-7.66(10H, m)
2082-Me—C6H4Me5-Me-1
imidazol-1-yl
2093-Me—C6H4Me5-Me-1
imidazol-1-yl
2104-Me—C6H4Me5-Me-1
imidazol-1-yl
2112-MeO—C6H4Me5-Me-1
imidazol-1-yl
2123-MeO—C6H4Me5-Me-1
imidazol-1-yl
2134-MeO—C6H4Me5-Me-1
imidazol-1-yl
2142,5-Me2—C6H3Me5-Me-1
imidazol-1-yl
215C6H5Et5-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl1.28(3H, t, J=7.3), 1.96(3H, s),
4.19(2H, q, J=7.3), 5.20(2H,
s), 6.86-7.72(11H, m)
2164-Cl—C6H4Et5-Me-1
imidazol-1-yl
2174-Me—C6H4Et5-Me-1
imidazol-1-yl
218C6H5Allyl5-Me-1
imidazol-1-yl
2194-Cl—C6H4Allyl5-Me-1
imidazol-1-yl
2204-Me—C6H4Allyl5-Me-1
imidazol-1-yl
221C6H5Me4-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl2.19(3H, s), 3.95(3H, s),
5.00(2H, s), 6.79-7.63(10H,
m), 7.90(1H ,s)
2222-F—C6H4Me4-Me-1
imidazol-1-yl
2233-F—C6H4Me4-Me-1
imidazol-1-yl
2244-F—C6H4Me4-Me-1
imidazol-1-yl
2252-Cl—C6H4Me4-Me-11H-NMR(CDCl3) δ]ppm:
imidazol-1-yl2.18(3H, d, J=1.2), 3.99(3H,
s), 5.05(2H, s), 6.77-7.72(9H,
m), 7.90(1H, d, J=1.2)
2263-Cl—C6H4Me4-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl2.19(3H, s), 3.96(3H, s),
4.99(2H, s), 6.95-7.59(9H, m),
7.88(1H, d, J=1.2)
2274-Cl—C6H4Me4-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl2.18(3H, s), 3.95(3H, s),
4.97(2H, s), 6.70-7.59(9H, m),
7.88(1H, d, J=1.2)
2282-Me—C6H4Me4-Me-1
imidazol-1-yl
2293-Me—C6H4Me4-Me-1
imidazol-1-yl
2304-Me—C6H4Me4-Me-1
imidazol-1-yl
2312-MeO—C6H4Me4-Me-1
imidazol-1 yl
2323-MeO—C6H4Me4-Me-1
imidazol-1-yl4-Me-
2334-MeO—C6H4Me4-Me-1
imidazol-1-yl
2342,5-Me2—C6H3Me4-Me-1
imidazol-1-yl
235C6H5Et4-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl1.30(3H, t, J=7.3), 2.19(3H, s),
4.21(2H, q, J=7.3), 5.02(2H,
s), 6.78-7.63(10H, m),
7.96(1H, s)
2364-Cl—C6H4Et4-Me-1
imidazol-1-yl
2374-Me—C6H4Et4-Me-1
imidazol-1-yl
238C6H5Allyl4-Me-1
imidazol-1-yl
2394-Cl—C6H4Allyl4-Me-1
imidazol-1-yl
2404-Me—C6H4Allyl4-Me-1
imidazol-1-yl
241C6H5Me2-Me-11H-NMR(CDCl3) δ ppm:
imidazol-1-yl2.21(3H, s), 3.93(3H, s),
5.18(2H, s), 6.89-7.71(11H, m)
2422-F—C6H4Me2-Me-1
imidazol-1-yl
2433-F—C6H4Me2-Me-1
imidazol-1-yl
2444-F—C6H4Me2-Me-1
imidazol-1-yl
2452-Cl—C6H4Me2-Me-1
imidazol-1-yl
2463-Cl—C6H4Me2-Me-1
imidazol-1-yl
2474-Cl—C6H4Me2-Me-1
imidazol-1-yl
2482-Me—C6H4Me2-Me-1
imidazol-1-yl
2493-Me—C6H4Me2-Me-1
imidazol-1-yl
2504-Me—C6H4Me2-Me-1
imidazol-1-yl
2512-MeO—C6H4Me2-Me-1
imidazol-1-yl
2523-MeO—C6H4Me2-Me-1
imidazol-1-yl
2534-MeO—C6H4Me2-Me-1
imidazol-1-yl
2542,5-Me2—C6H3Me2-Me-1
imidazol-1-yl
255C6H5Et2-Me-1
imidazol-1-yl
2564-Cl—C6H4Et2-Me-1
imidazol-1-yl
2574-Me—C6H4Et2-Me-1
imidazol-1-yl
258C6H5Allyl2-Me-1
imidazol-1-yl
2594-Cl—C6H4Allyl2-Me-1
imidazol-1-yl
2604-Me—C6H4Allyl2-Me-1
imidazol-1-yl
261C6H5Me1H-1,2,4-1mp 86-87° C.
Triazol-1-yl
2622-F—C6H4Me1H-1,2,4-1
Triazol-1-yl
2633-F—C6H4Me1H-1,2,4-1
Triazol-1-yl
2644-F—C6H4Me1H-1,2,4-1
Triazol-1-yl
2652-Cl—C6H4Me1H-1,2,4-1mp 101.5-102.5° C.
Triazol-1-yl
2663-Cl—C6H4Me1H-1,2,4-11H-NMR(CDCl3) δ ppm:
Triazol-1-yl4.06(3H, s), 4.94(2H, s), 6.63-
7.65(8H, m), 7.96(1H, s),
9.12(1H, s)
2674-Cl—C6H4Me1H-1,2,4-1mp 101-102° C.
Triazol-1-yl
2682-Me—C6H4Me1H-1,2,4-1
Triazol-1-yl
2693-Me—C6H4Me1H-1,2,4-1
Triazol-1-yl
2704-Me—C6H4Me1H-1,2,4-1mp 98.5-99.5° C.
Triazol-1-yl
2712-MeO—C6H4Me1H-1,2,4-1
Triazol-1-yl
2723-MeO—C6H4Me1H-1,2,4-1
Triazol-1-yl
2734-MeO—C6H4Me1H-1,2,4-1
Triazol-1-yl
2742,5-Me2—C6H3Me1H-1,2,4-1mp 96° 98° C.
Triazol-1-yl
275C6H5Et1H-1,2,4-1mp 78.5-80.5° C.
Triazol-1-yl
2764-Cl—C6H4Et1H-1,2,4-1
Triazol-1-yl
2774-Me—C6H4Et1H-1,2,4-1
Triazol-1-yl
278C6H5Allyl1H-1,2,4-11H-NMR(CDCl3) δ ppm: 4.71-
Triazol-1-yl4.74(2H, m), 4.94(2H, s), 5.25-
5.37(2H, m), 5.91-6.06(1H, m),
6.76-7.59(9H, m), 7.96(1H, s),
9.13(1H, s)
2794-Cl—C6H4Allyl1H-1,2,4-1
Triazol-1-yl
2804-Me—C6H4Allyl1H-1,2,4-1
Triazol-1-yl
281C6H5MePyrazol-1-yl11H-NMR(CDCl3) δ ppm:
4.02(3H, s), 4.78(2H, s),
6.40(1H, dd, J=3.1, 1.8), 6.78-
7.62(10H, m), 8.42(1H, d,
J=2.4)
2822-F—C6H4MePyrazol-1-yl1
2833-F—C6H4MePyrazol-1-yl1
2844-F—C6H4MePyrazol-1-yl1
2852-Cl—C6H4MePyrazol-1-yl1mp 90-91° C.
2863-Cl—C6H4MePrazol-1-yl11H-NMR(CDCl3) δ ppm:
4.26(3H, s), 4.78(2H, s), 6.42-
7.62(10H, m), 8.45(1H, d,
J=2.4)
2874-Cl—C6H4MePyrazol-1-yl1mp 94-95° C.
2882-Me—C6H4MePyrazol-1-yl1
2893-Me—C6H4MePyrazol-1-yl1
2904-Me—C6H4MePyrazol-1-yl1mp 82-83° C.
2912-Cl-MePyrazol-1-yl1mp 87.5-88.5° C.
pyridin-3-yl
2923-MeO—C6H4MePyrazol-1-yl1
2934-MeO—C6H4MePyrazol-1-yl1
2942,5-Me2—C6H3MePyrazol-1-yl1mp 78-80° C.
295C6H5EtPyrazol-1-yl11H-NMR(CDCl3) δ ppm:
1.36(3H, t, J=6.7), 4.27(2H, q,
J=6.7), 4.79(2H, s), 6.40-
7.61 (11H, m), 8.48(1H, d,
J=3.1)
2964-Cl—C6H4EtPyrazol-1-yl1
2974-Me—C6H4EtPyrazol-1-yl1
298C6H5AllylPyrazol-1-yl11H-NMR(CDCl3) δ ppm: 4.69-
4.73(2H, m), 4.80(2H, s), 5.23-
5.38(2H, m), 5.96-6.10(1H, m),
6.40-7.62(11H, m), 8.48(1H, d,
J=2.4)
2994-Cl—C6H4AllylPyrazol-1-yl1
300C6H5MePyrazol-1-yl01H-NMR(CDCl3) δ ppm:
4.03(3H, s), 6.34(1H, t, J=2.9),
6.82-7.63(10H, m), 8.37(1H,
d, J=2.9)
301C6H5MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
4.06(3.99)(3H, s),
5.05(4.96)(2H, s), 6.73-
7.61(10H, m), 8.46(8.39)(1H,
d, J=1.8)
3022-F—C6H4MeIsoxazol-3-yl1
3033-F—C6H4MeIsoxazol-3-yl1
3044-F—C6H4MeIsoxazol-3-yl1
3052-Cl—C6H4MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
4.08(4.01)(3H, s),
5.14(5.12)(2H, s), 6.76-
7.68(9H, m), 8.46(8.40)(1H, d,
J=1.8)
3063-Cl—C6H4MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
4.07(4.01)(3H, s),
5.04(4.95)(2H, s), 6.70-
7.56(9H, m), 8.48(8.40)(1H, d,
J=1.8)
3074-Cl—C6H4MeIsoxazol-3-yl14.06(3.99)(3H, s),
5.03(4.94)(3H, s),
6.72-7.56(9H, m),
8.47(8.39)(1H, d, J=1.8)
3082-Br—C6H4MeIsoxazol-3-yl1
3093-Br—C6H4MeIsoxazol-3-yl1
3104-Br—C6H4MeIsoxazol-3-yl1
3113-I—C6H4MeIsoxazol-3-yl1
3122-Me—C6H4MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
2.20(2.17)(3H, s),
4.07(4.00)(3H, s),
5.03(4.97)(2H, s), 6.68-
7.64(9H, m), 8.44(8.39)(1H, d,
J=1.8)
3133-Me—C6H4MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
2.29(2.27)(3H, s),
4.07(4.00)(3H, s),
5.03(4.95)(2H, s), 6.62-
7.61(9H, m), 8.47(8.39)(1H, d,
J=1.8)
3144-Me—C6H4MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
2.25(3H, s), 4.06(3.99)(3H, s),
5.01(4.93)(2H, s), 6.70-
7.60(9H, m), 8.46(8.39)(1H, d,
J=1.8)
3152-Et—C6H4MeIsoxazol-3-yl1
3163-Et—C6H4MeIsoxazol-3-yl1
3174-Et—C6H4MeIsoxazol-3-yl1
3182-MeO—C6H4MeIsoxazol-3-yl1
3193-MeO—C6H4MeIsoxazol-3-yl1
3204-MeO—C6H4MeIsoxazol-3-yl1
3212-CF3—C6H4MeIsoxazol-3-yl1
3223-CF3—C6H4MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
4.05(3.98)(3H, s),
5.10(5.01)(2H, s), 6.74(1H, d,
J=1.8), 6.94-7.57(8H, m),
8.47(8.40)(1H, d, J=1.8)
3234-CF3—C6H4MeIsoxazol-3-yl1
3242,4-F2—C6H3MeIsoxazol-3-yl1
3252,5-F2—C6H3MeIsoxazol-3-yl1
3262,6-F2—C6H3MeIsoxazol-3-yl1
3273,4-F2—C6H3MeIsoxazol-3-yl1
3283,5-F2—C6H3MeIsaxazol-3-yl1
3292,3-Cl2—C6H3MeIsoxazol-3-yl1
3302,4-Cl2—C6H3MeIsoxazol-3-yl1
3312,5-Cl2—C6H3MeIsoxazol-3-yl1
3323,4-Cl2—C6H3MeIsoxazol-3-yl1
3333,5-Cl2—C6H3MeIsoxazol-3-yl1
3342,3-Me2—C6H3MeIsoxazol-3-yl1
3352,4-Me2—C6H3MeIsoxazol-3-yl1
3362,5-Me2—C6H3MeIsoxazol-3-yl1mp 104-108° C.
3373,4-Me2—C6H3MeIsoxazol-3-yl1
3383,5-Me2—C6H3MeIsoxazol-3-yl1
3392-Cl-4-Me—C6H3MeIsoxazol-3-yl1
3402-Cl-5-Me—C6H3MeIsoxazol-3-yl1
3414-Cl-2-Me—C6H3MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
2.16(2.13)(3H, s),
4.07(3.99)(3H, s),
5.01 (4.95)(2H, s), 6.59-
7.58(8H, m), 8.45(8.40)(1H, d,
J=1.8)
3424-Cl-3-Me—C6H3MeIsoxazol-3-yl1
3433-Ph—C6H4MeIsoxazol-3-yl1
3444-Ph—C6H4MeIsoxazol-3-yl1
3453-i-PrO—C6H4MeIsoxazol-3-yl1
3463-i-Pr—C6H4MeIsoxazol-3-yl1
3474-i-Pr—C6H4MeIsoxazol-3-yl1
3483-t-Bu—C6H4MeIsoxazol-3-yl1
3492-MeS—C6H4MeIsoxazol-3-yl1
3504-MeS—C6H4MeIsoxazol-3-yl1
3512,3,6-F3—C6H2MeIsoxazol-3-yl1
3522,4,5-Cl3—C6H2MeIsoxazol-3-yl1
3533-PhO—C6H4MeIsoxazol-3-yl1
3543,4,5-(MeO)3—C6H2MeIsoxazol-3-yl1
3552,3,5-Me3p13 C6H2MeIsoxazol-3-yl1
3563,4,5-Me3—C6H2MeIsoxazol-3-yl1
357C6F5MeIsoxazol-3-yl1
3584-Cl-3-Et—C6H3MeIsoxazol-3-yl1
3593-EtO—C6H4MeIsoxazol-3-yl1
3604-EtO—C6H4MeIsoxazol-3-yl1
361C6H5MeIsoxazol-3-yl0
3624-F—C6H4MeIsoxazol-3-yl0
3633-Cl—C6H4MeIsoxazol-3-yl0
3644-Cl—C6H4MeIsoxazol-3-yl0
3653-Me—C6H4MeIsoxazol-3-yl0
3664-Me—C6H4MeIsoxazol-3-yl0
3674-Et—C6H4MeIsoxazol-3-yl0
3684-NO2—C6H4MeIsoxazol-3-yl0
3693,4-C2—C6H3MeIsoxazol-3-yl0
3703,5-Cl2—C6H3MeIsoxazol-3-yl0
3713,4-Me2—C6H3MeIsoxazol-3-yl0
3723,5-Me2—C6H3MeIsoxazol-3-yl0
3733-PhO—C6H4MeIsoxazol-3-yl0
3744-Cl-3-Et—C6H3MeIsoxazol-3-yl0
3753-EtO—C6H4MeIsoxazol-3-yl0
3763-CF3—C6H4MeIsoxazol-3-yl0
3774-CF3—C6H4MeIsoxazol-3-yl0
3783-i-PrO—C6H4MeIsoxazol-3-yl0
3793-i-Pr—C6H4MeIsoxazol-3-yl0
3804-Cl-3-Me—C6H3MeIsoxazol-3-yl0
381pyridin-2-ylMeIsoxazol-3-yl1
382pyridin-3-ylMeIsoxazol-3-yl1
3835-Cl-MeIsoxazol-3-yl1
pyridin-2-yl
3843-Cl-MeIsoxazol-3-yl1
pyridin-2-yl
3856-Cl-MeIsoxazol-3-yl1
pyridin-2-yl
3862-Cl-MeIsoxazol-3-yl1
pyridin-3-yl
3875-CF3-MeIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
pyridin-2-yl3.98(3H. s), 5.32(2H, s),
6.63(1H, d, J=8.5), 6.73(1H, d,
J=1.8), 7.27-7.71(5H, m),
8.30(1H; s), 8.39(1 H, d, J=1.8)
3883-CF3-MeIsoxazol-3-yl1mp 125-126.5° C.
pyridin-2-yl
3896-CF3-3-Cl-MeIsoxazol-3-yl1
pyridin-2-yl
3905-CF-3-Cl-MeIsoxazol-3-yl11H-NMR(CDCl3) δ
pyridin-2-ylppm: 4.00(3H, s), 5.41(2H, s),
6.76(1H, d, J=1.8), 7.27-
7.78(5H, m), 8.15(1H, s),
8.46(1H, d, J=1.8)
391Benzothiazol-MeIsoxazol-3-yl1
2-yl
392Benzoxazol-MeIsoxazol-3-yl1
2-yl
393Quinolin-2-ylMeIsoxazol-3-yl1
3945-CF3-1,3,4-MeIsoxazol-3-yl1
thiadiazol-2-yl
395pyrimidin-2-ylMeIsoxazol-3-yl1
3965-Cl-6-Me-MeIsoxazol-3-yl1
pyrimidin-4-yl
3975-Et-6-Me-MeIsoxazol-3-yl1
pyrimidin-4-yl
3986-Cl-MeIsoxazol-3-yl1
pyrazin-2-yl
3993,6-Me2-MeIsoxazol-3-yl1
pyrazin-2-yl
4005-Me-MeIsoxazol-3-yl1
Isoxazol-3-yl
401C6H5Me5-Me-12.43(3H, s), 3.97(4.04)(3H, s),
isoxazol-3-yl4.96(5.06)(2H, s),
6.35(6.55)(1H, s), 6.83-
7.60(9H, m)
4022-F—C6H4Me5-Me-1
isoxazol-3-yl
4033-F—C6H4Me5-Me-1
isoxazol-3-yl
4044-F—C6H4Me5-Me-1
isoxazol-3-yl
4052-Cl—C6H4Me5-Me-11H-NMR(CDCl3) δ ppm:
isoxazol-3-yl2.44(3H, s), 4.07(3.98)(3H, s),
5.15(5.06)(2H, s), 6.38(
6.57)(1H, s), 6.78-7.66(8H, m)
4063-Cl—C6H4Me5-Me-1mp 111.0-123.0° C.
isoxazol-3-yl
4074-Cl—C6H4Me5-Me-1mp 74.0-85.0° C.
isoxazol-3-yl
4082-Br—C6H4Me5-Me-1
isoxazol-3-yl
4093-Br—C6H4Me5-Me-1
isoxazol-3-yl
4104-Br—C6H4Me5-Me-1
isoxazol-3-yl
4113-I—C6H4Me5-Me-1
isoxazol-3-yl
4122-Me—C6H4Me5-Me-11H-NMR(CDCl3) δ ppm:
isoxazol-3-yl2.20(2.22)(3H, s),
2.42(2.42)(3H, s),
3.98(4.06)(3H, s),
4.97(5.04)(2H, s),
6.35(6.53)(1H, s), 6.69-
7.63(8H, m)
4133-Me—C6H4Me5-Me-1mp 92.0-93.0° C.
isoxazol-3-yl
4144-Me—C6H4Me5-Me-1mp 104.0-105.5° C.
isoxazol-3-yl
4152-Et—C6H4Me5-Me-1
isoxazol-3-yl
4163-Et—C6H4Me5-Me-1
isoxazol-3-yl
4174-Et—C6H4Me5-Me-1
isoxazol-3-yl
4182-MeO—C6H4Me5-Me-1
isoxazol-3-yl
4193-MeO—C6H4Me5-Me-1
isoxazol-3-yl
4204-MeO—C6H4Me5-Me-1
isoxazol-3-yl
4212-CF3—C6H4Me5-Me-1
isoxazol-3-yl
4223-CF3—C6H4Me5-Me-11H-NMR(CDCl3) δ ppm:
isoxazol-3-yl2.43(2.44)(3H, s),
4.03(3.97)(3H, s),
5.00(5.09)(2H, s), 6.35(1H, s),
6,56(6.57)(1H, s), 7.00-
7.64(7H, m)
4234-CF3—C6H4Me5-Me-1
isoxazol-3-yl
4242,4-F2—C6H3Me5-Me-1
isoxazol-3-yl
4252,5-F2—C6H3Me5-Me-1
isoxazol-3-yl
4262,6-F2—C6H3Me5-Me-1
isoxazol-3-yl
4273,4-F2—C6H3Me5-Me-1
isoxazol-3-yl
4283,5-F2—C6H3Me5-Me-1
isoxazol-3-yl
4292,3-Cl2—C6H3Me5-Me-1
isoxazol-3-yl
4302,4-Cl2C6H3Me5-Me-1
isoxazol-3-yl
4312,5-Cl2-C6H3Me5-Me-1
isoxazol-3-yl
4323,4-Cl2—C6H3Me5-Me-1
isoxazol-3-yl
4333,5-Cl2—C6H3Me5-Me-1
isoxazol-3-yl
4342,3-Me2—C6H3Me5-Me-1
isoxazol-3-yl
4352,4-Me2—C6H3Me5-Me-1
isoxazol-3-yl
4362,5-Me2—C6H3Me5-Me-11H-NMR(CDCl3) δ ppm:
isoxazol-3-yl2.15(2.16)(3H, s),
2.24(2.25)(3H, s),
2.42(2.43)(3H, s),
3.99(4.07)(3H, s),
4.95(5.01)(2H, s), 6.36-
7.64(8H, m)
4373,4-Me2—C6H3Me5-Me-1
isoxazol-3-yl
4383,5-Me2—C6H3Me5-Me-1
isoxazol-3-yl
4392-Cl-4-Me—C6H3Me5-Me-1
isoxazol-3-yl
4402-Cl-5-Me—C6H3Me5-Me-1
isoxazol-3-yl
4414-Cl-2-Me—C6H3Me5-Me-1mp 79-83° C.
isoxazol-3-yl
4424-Cl-3-Me—C6H3Me5-Me-1
isoxazol-3-yl
4433-Ph—C6H4Me5-Me-1
isoxazol-3-yl
4444-Ph—C6H4Me5-Me-1mp 105.0-115.° C.
isoxazol-3-yl
4453-i-PrO—C6H4Me5-Me-1
isoxazol-3-yl
4463-i-Pr—C6H4Me5-Me-1
isoxazol-3-yl
4474-i-Pr—C6H4Me5-Me-1
isoxazol-3-yl
4483-t-Bu—C6H4Me5-Me-1
isoxazol-3-yl
4492-MeS—C6H4Me5-Me-1
isoxazol-3-yl
4504-MeS—C6H4Me5-Me-1
isoxazol-3-yl
4512,3,6-F3—C6H2Me5-Me-1
isoxazol-3-yl
4522,4,5-Cl3—6H2Me5-Me-1
isoxazol-3-yl
4533-PhO—C6H4Me5-Me-1
isoxazol-3-yl
4543,4,5-(MeO)3—C6H2Me5-Me-1
isoxazol-3-yl
4552.3.5-(Me3—C6H2Me5-Me-1
isoxazol-3-yl
4563,4,5-Me3—C6H2Me5-Me-1
isoxazol-3-yl
457C6F5Me5-Me-1
isoxazol-3-yl
4584-Cl-3-Et—C6H3Me5-Me-1
isoxazol-3-yl
4593-EtO—C6H4Me5-Me-1
isoxazol-3-yl
4604-EtO—C6H4Me5-Me-1
isoxazol-3-yl
461C6H5Me5-Me-0
isoxazol-3-yl
4624-F—C6H4Me5-Me-0
isoxazol-3-yl
4633-Cl—C6H4Me5-Me-0
isoxazol-3-yl
4644-Cl—C6H4Me5-Me-0
isoxazol-3-yl
4653-Me—C6H4Me5-Me-0
isoxazol-3-yl
4664-Me—C6H4Me5-Me-0
isoxazol-3-yl
4674-Et—C6H4Me5-Me-0
isoxazol-3-yl
4684-NO2—C6H4Me5-Me-0
isoxazol-3-yl
4693,4-Cl2—C6H3Me5-Me-0
isoxazol-3-yl
4703,5-Cl2—C6H3Me5-Me-0
isoxazol-3-yl
4713,4-Me2—C6H3Me5-Me-0
isoxazol-3-yl
4723,5-Me2—C6H3Me5-Me-0
isoxazol-3-yl
4733-PhO—C6H4Me5-Me-0
isoxazol-3-yl
4744-Cl-3-Et—C6H3Me5-Me-0
isoxazol-3-yl
4753-EtO—C6H4Me5-Me-0
isoxazol-3-yl
4763-CF3—C6H4Me5-Me-0
isoxazol-3-yl
4774-CF3—C6H4Me5-Me-0
isaxazol-3-yl
4783-i-PrO—C6H4Me5-Me-0
isoxazol-3-yl
4793-i-Pr—C6H4Me5-Me-0
isoxazol-3-yl
4804-Cl-3-Me—C6H3Me5-Me-0
isoxazol-3-yl
481Pyridin-2-ylMe5-Me-1
isoxazol-3-yl
482Pyridin-3-ylMe5-Me-1
isoxazol-3-yl
4835-Cl-Me5-Me-1
pyridin-2-ylisoxazol-3-yl
4843-Cl-Me5-Me-11H-NMR(CDCl3) δ
pyridin-2-ylisoxazol-3-ylppm: 2.42(3H, s), 3.97(3H, s),
5.35(2H, s), 6.35(1H, s), 6.76-
6.81(1H, m), 7.24-7.93(6H, m).
4856-Cl-Me5-Me-1
pyridin-2-ylisoxazol-3-yl
4862-Cl-Me5-Me-1
pyridin-3-ylisoxazol-3-yl
4875-CF3-Me5-Me-11H-NMR(CDCL3) δ
pyridin-2-ylisoxazol-3-ylppm: 2.43(3H, s), 3.96(3H, s),
5.32(2H, s), 6.34(1H, d,
J=1.2), 6.67(1 H, d, J=8.5),
7.24-7.72(5H, m), 8.31(1H, s)
4883-CF3-Me5-Me-1
pyridin-2-ylisoxazol-3-yl
4896-CF3-3-Cl-Me5-Me-1
pyridin-2-ylisoxazol-3-yl
4905-CF3-3-Cl-Me5-Me-11H-NMR(CDCl3) δ
pyridin-2-ylisoxazol-3-ylppm:2.43(3H, s), 3.97(3H, s),
5.40(2H, s), 6.37(1H, s), 7.25-
8.17(6H, m).
491Benzothiazol-Me5-Me-1
2-ylisoxazol-3-yl
492Benzoxazol-Me5-Me-1
2-ylisoxazol-3-yl
493Quinolin-2-ylMe5-Me-1
isoxazol-3-yl
4945-CF3-1,3,4-Me5-Me-1
thiadiazol-2-ylisoxazol-3-yl
495Pyrimidin-2-ylMe5-Me-1
isoxazol-3-yl
4965-Cl-6-Me-Me5-Me-1
pyrimidin-4-ylisoxazol-3-yl
4975-Et-6-Me-Me5-Me-1
pyrimidin-4-ylisoxazol-3-yl
4986-Cl-Me5-Me-1
pyrazin-2-ylisoxazol-3-yl
4993,6-Me2-Me5-Me-1
pyrazin-2-ylisoxazol-3-yl
5005-Me-Me5-Me-1
isoxazol-3-ylisoxazol-3-yl
501C6H5MeIsoxazol-5-yl1
5022-F—C6H4MeIsoxazol-5-yl1
5033-F—C6H4MeIsoxazol-5-yl1
5044-F—C6H4MeIsoxazol-5-yl1
5052-Cl—C6H4MeIsoxazol-5-yl1
5063-Cl—C6H4MeIsoxazol-5-yl1
5074-Cl—C6H4MeIsoxazol-5-yl1Isomer A: 1H-NMR(CDCl3) δ
ppm: 4.11(3H, s), 4.99(2H, s),
6.68-6.73(2H, m), 7.11(1H, d,
J=1.8), 7.14-7.18(2H, m),
7.40-7.57(4H, m), 8.34(1H, d,
J=1.8)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 4.03(3H, s), 4.92(2H, s),
6.21(1H, d, J=1.8), 6.68-
6.74(2H, m), 7.13-7.23(3H, m),
7.41-7.61(3H, m), 8.24(1H, d,
J=1.8)
5082-Br—C6H4MeIsoxazol-5-yl1
5093-Br—C6H4MeIsoxazol-5-yl1
5104-Br—C6H4MeIsoxazol-5-yl1
5113-I—C6H4MeIsoxazol-5-yl1
5122-Me—C6H4MeIsoxazol-5-yl1Isomer A: mp 7l.5-72.5° C.
Isomer B: mp 68.0-69.0° C.
5133-Me—C6H4MeIsoxazol-5-yl1
5144-Me—C6H4MeIsoxazol-5-yl1
5152-Et—C6H4MeIsoxazol-5-yl1
5163-Et—C6H4MeIsoxazol-5-yl1
5174-Et—C6H4MeIsoxazol-5-yl1
5182-MeO—C6H4MeIsoxazol-5-yl1
5193-MeO—C6H4MeIsoxazol-5-yl1
5204-MeO—C6H4MeIsoxazol-5-yl1
5212-CF3—C6H4MeIsoxazol-5-yl1
5223-CF3—C6H4MeIsoxazol-5-yl1Isomer A: 1H-NMR(CDCl3) δ
ppm: 4.10(3H, s), 5.07(2H, s),
6.91-7.02(2H, m), 7.11(1H, d,
J=1.8), 7.15-7.59(6H, m),
8.34(1H, d, J=1.8)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 4.03(3H, s), 4.99(2H, s),
6.22(1H, d, J=1.8), 6.92-
7.62(8H, m), 8.24(1H, d,
J=1.8)
5234-CF3—C6H4MeIsoxazol-5-yl1
5242,4-F2—C6H3MeIsoxazol-5-yl1
5252,5-F2—C6H3MeIsoxazol-5-yl1
5262,6-F2—C6H3MeIsaxazol-5-yl1
5273,4-F2—C6H3MeIsoxazol-5-yl1
5283,5-F2—C6H3MeIsoxazol-5-yl1
5292,3-Cl2—C6H3MeIsoxazol-5-yl1
5302,4-Cl2—C6H3MeIsoxazol-5-yl1
5312,5-Cl2—C6H3MeIsoxazol-5-yl1
5323,4-Cl2—C6H3MeIsoxazol-5-yl1
5333,5-Cl2—C6H3MeIsoxazol-5-yl1
5342,3-Me2—C6H3MeIsoxazol-5-yl1
5352,4-Me2—C6H3MeIsoxazol-5-yl1
5362,5-Me2—C6H3MeIsoxazol-5-yl1Isomer A: mp 137.5-138.5° C.
Isomer B: mp 93.0-94.5° C.
5373,4-Me2—C6H3MeIsoxazol-5-yl1
5383,5-Me2—C6H3MeIsoxazol-5-yl1
5392-Cl-4-Mep—C6H3MeIsoxazol-5-yl1
5402-Cl-5-Me—C6H3MeIsoxazol-5-yl1
5414-Cl-2-Me—C6H3MeIsoxazol-5-yl1Isomer A: mp 84.0-85.0° C.
Isomer B: 1H-NMR(CDCl3) δ
ppm: 2.16(3H, s), 4.04(3H, s),
4.93(2H, s), 6.20(1H, d,
J=1.8), 6.62(1H, d, J=8.5),
6.99-7.63(6H, m), 8.22(1H, d,
J=1.8)
5424-Cl-3-Me—C6H3MeIsoxazol-5-yl1
5433-Ph—C6H4MeIsoxazol-5-yl1
5444-Ph—C6H4MeIsoxazol-5-yl1
5453-i-PrO—C6H4MeIsoxazol-5-yl1
5463-i-Pr—C6H4MeIsoxazol-5-yl1
5474-i-Pr—C6H4MeIsoxazol-5-yl1
5483-t-Bu—C6H4MeIsoxazol-5-yl1
5492-MeS—C6H4MeIsoxazol-5-yl1
5504-MeS—C6H4MeIsoxazol-5-yl1
5512,3,6-F3—C6H2MeIsoxazol-5-yl1
5522,4,5-Cl3—C6H2MeIsoxazol-5-yl1
5533-PhO—C6H4MeIsoxazol-5-yl1
5543,4,5-(MeO)3—C6H2MeIsoxazol-5-yl1
5552,3,5-Me3—C6H2MeIsoxazol-5-yl1
5563,4,5-Me3—C6H2MeIsoxazol-5-yl1
557C6F5MeIsoxazol-5-yl1
5584-Cl-3-Et—C6H3MeIsoxazol-5-yl1
5593-EtO—C6H4MeIsaxazol-5-yl1
5604-EtO—C6H4MeIsoxazol-5-yl1
561C6H5MeIsoxazol-5-yl0
5624-F—C6H4MeIsoxazol-5-yl0
5633-Cl—C6H4MeIsoxazol-5-yl0
5644-Cl—C6H4MeIsoxazol-5-yl0
5653-Me—C6H4MeIsoxazol-5-yl0
5664-Me—C6H4MeIsoxazol-5-yl0
5674-Et—C6H4MeIsoxazol-5-yl0
5684-NO2—C6H4MeIsoxazol-5-yl0
5693,4-Cl2—C6H3MeIsoxazol-5-yl0
5703,5-Cl2—C6H3MeIsoxazol-5-yl0
5713,4-Me2—C6H3MeIsoxazol-5-yl0
5723,5-Me2—C6H3MeIsoxazol-5-yl0
5733-PhO—C6H4MeIsoxazol-5-yl0
5744-Cl-3-Et—C6H3MeIsoxazol-5-yl0
5753-EtO—C6H4MeIsoxazol-5-yl0
5763-CF3—C6H4MeIsoxazol-5-yl0
5774-CF3—C6H4MeIsoxazol-5-yl0
5783-i-PrO—C6H4MeIsoxazol-5-yl0
5793-i-Pr—C6H4MeIsoxazol-5-yl0
5804-Cl-3-Me—C6HMeIsoxazol-5-yl0
581Pyridin-2-ylMeIsoxazol-5-yl1
582Pyridin-3-ylMeIsoxazol-5-yl1
5835-Cl-MeIsoxazol-5-yl1
pyridin-2-yl
5843-Cl-MeIsoxazol-5-yl1
pyridin-2-yl
5856-Cl-MeIsoxazol-5-yl1
pyridin-2-yl
5862-Cl-MeIsoxazol-5-yl1
pyridin-3-yl
5875-CF3-MeIsoxazol-5-yl1
pyridin-2-yl
5883-CF3-MeIsoxazol-5-yl1
pyridin-2-yl
5896-CF3-3-Cl-MeIsoxazol-5-yl1
pyridin-2-yl
5905-CF3-3-Cl-Meisoxazol-5-yl1
pyridin-2-yl
591Benzothiazol-MeIsoxazol-5-yl1
2-yl
592Benzoxazol-MeIsoxazol-5-yl1
2-yl
593Quinolin-2-ylMeIsoxazol-5-yl1
5945-CF3-1,3,4-MeIsoxazol-5-yl1
thiadiazol-2-yl
595Pyrimidin-2-ylMeIsoxazol-5-yl1
5965-Cl-6-Me-MeIsoxazol-5-yl1
pyrimidin-4-yl
5975-Et-6-Me-MeIsoxazol-5-yl1
pyrimidin-4-yl
5986-Cl-MeIsoxazol-5-yl1
Pyrazin-2-yl
5993,6-Me2-MeIsoxazol-5-yl1
Pyrazin-2-yl
6005-Me-MeIsoxazol-5-yl1
isoxazol-3-yl
601C6H5Me3-Me-1Isomer A: mp 99.0-100.0° C.
isoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.27(3H, s), 4.02(3H, s),
4.95(2H, s), 5.99(1H, s), 6.80-
7.65(9H, m)
6022-F—C6H4Me3-Me-1
isoxazol-5-yl
6033-F—C6H4Me3-Me-1
isoxazol-5-yl
6044-F—C6H4Me3-Me-1
isoxazol-5-yl
6052-Cl—C6H4Me3-Me-1Isomer A: mp 87.0-88.0° C.
isoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.27(3H, s), 4.04(3H, s),
5.01(2H, s), 6.02(1H, s), 6.81-
7.74(8H, m)
6063-Cl—C6H4Me3-Me-1Isomer A: 1H-NMR(CDCl3) δ
isoxazol-5-ylppm: 2.35(3H, s), 4.10(3H, s),
5.00(2H, s), 6.66-6.91(3H, m),
6.94(1H, s), 7.10-7.57(5H, m).
Isomer B: 1H-NMR(CDCl3) δ
ppm: 2.28(3H, s), 4.03(3H, s),
4.94(2H, s), 6.01(1H, s), 6.68-
7.65(8H, m)
6074-Cl-C6H4Me3-Me-1Isomer A: mp 110.0-111.0° C.
isoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.27(3H, s), 4.01(3H, s),
4.92(2H, s), 5.99(1H, s), 6.71-
7.60(8H, m)
6082-Br—C6H4Me3-Me-1
isoxazol-5-yl
6093-Br—C6H4Me3-Me-1
isoxazol-5-yl
6104-Br—C6H4Me3-Me-1
isoxazol-5-yl
6113-I—C6H4Me3-Me-1
isoxazol-5-yl
6122-Me—C6H4Me3-Me-1Isomer A: mp 80.0-81.0° C.
isoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.17(3H, s), 2.26(3H, s),
4.03(3H, s), 4.93(2H, s),
5.98(1H, s), 6.71-7.68(8H, m)
6133-Me—C6H4Me3-Me-1Isomer A: mp 109.0-110.0° C.
isoxazol-5-ylIsomer B: mp 94.5-95.5° C.
6144-Me—C6H4Me3-Me-1Isomer A: mp 126.0-127.0° C.
isoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.25(3H, s), 2.27(3H, s),
4.02(3H, s), 4.92(2H, s),
5.99(1H, s), 6.70-7.64(8H, m)
6152-Et—C6H4Me3-Me-1
isoxazol-5-yl
6163-Et—C6H4Me3-Me-1
isoxazol-5-yl
6174-Et—C6H4Me3-Me-1
isoxazol-5-yl
6182-MeO—C6H4Me3-Me-1
isoxazol-5-yl
6193-MeO—C6H4Me3-Me-1
isoxazol-5-yl
6204-MeO—C6H4Me3-Me-1
isoxazol-5-yl
6212-CF3—C6H4Me3-Me-1
isoxazol-5-yl
6223-CF3—C6H4Me3-Me-1Isomer A: 1H-NMR(CDCl3) δ
isoxazol-5-ylppm: 2.34(3H, s), 4.08(3H, s),
5.05(2H, s), 6.92(1H, s), 6.94-
7.57(8H, m)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 2.27(3H, s), 4.02(3H, s),
4.99(2H, s), 6.01(1H, s), 6.96-
7.61 (8H, m)
6234-CF3—C6H4Me3-Me-1
isoxazol-5-yl
6242,4-F2—C6H3Me3-Me-1
isoxazol-5-yl
6252,5-F2—C6H3Me3-Me-1
isoxazol-5-yl
6262,6-F2—C6H3Me3-Me-1
isoxazol-5-yl
6273,4-F2—C6H3Me3-Me-1
isoxazol-5-yl
6283,5-F2—C6H3Me3-Me-1
isoxazol-5-yl
6292,3-Cl2—C6H3Me3-Me-1
isoxazol-5-yl
6302,4-Cl2—C6H3Me3-Me-1
isoxazol-5-yl
6312,5-Cl2—C6H3Me3-Me-1
isoxazol-5-yl
6323,4-Cl2—C6H3Me3-Me-1
isoxazol-5-yl
6333,5-Cl2—C6H3Me3-Me-1
isoxazol-5-yl
6342,3-Me2—C6H3Me3-Me-1
isoxazol-5-yl
6352,4-Me2—C6H3Me3-Me-1
isoxazol-5-yl
6362,5-Me2—C6H3Me3-Me-1Isomer A mp 113-114° C.
isoxazol-5-ylIsomer B mp 107-108° C.
6373,4-Me2—C6H3Me3-Me-1
isoxazol-5-yl
6383,5-Me2—C6H3Me3-Me-1
isoxazol-5-yl
6392-Cl-4-Me—C6H3Me3-Me-1
isoxazol-5-yl
6402-Cl-5-Me—C6H3Me3-Me-1
isoxazol-5-yl
6414-Cl-2-Me—C6H3Me3-Me-1Isomer A: mp 76.5-77.5° C.
isoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.12(3H, s), 2.26(3H, s),
4.03(3H, s), 4.93(2H, s),
5.97(1H, s), 6.62(1H, d,
J=8.5), 6.99-7.62(6H, m)
6424-Cl-3-Me—C6H3Me3-Me-1
isoxazol-5-yl
6433-Ph—C6H4Me3-Me-1
isoxazol-5-yl
6444-Ph—C6H4Me3-Me-1Isomer A: mp 130.5-131.5° C.
isoxazol-5-ylIsomer B: mp 102.5-103.5° C.
6453-i-PrO—C6H4Me3-Me-1
isoxazol-5-yl
6463-i-Pr—C6H4Me3-Me-1
isoxazol-5-yl
6474-i-Pr—C6H4Me3-Me-1
isoxazol-5-yl
6483-t-Bu—C6H4Me3-Me-1
isoxazol-5-yl
6492-MeS—C6H4Me3-Me-1
isoxazol-5-yl
6504-MeS—C6H4Me3-Me-1
isoxazol-5-yl
6512,3,6-F3—C6H2Me3-Me-1
isoxazol-5-yl
6522,4,5-Cl3—C6H2Me3-Me-1
isoxazol-5-yl
6533-PhO—C6H4Me3-Me-1
isoxazol-5-yl
6543,4,5-(MeO)3—C6H2Me3-Me-1
isoxazol-5-yl
6552,3,5-Me3—C6H2Me3-Me-1
isoxazol-5-yl
6563,4,5-Me3—C6H2Me3-Me-1
isoxazol-5-yl
657C6F5Me3-Me-1
isoxazol-5-yl
6584-Cl-3-Et—C6H3Me3-Me-1
isoxazol-5-yl
6593-EtO—C6H4Me3-Me-1
isoxazol-5-yl
6604-EtO—C6H4Me3-Me-1
isoxazol-5-yl
661C6H5Me3-Me-0Isomer A: mp 100.0-105.5° C.
isoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.28(3H, s), 3.94(3H, s),
6.17(1H, s),
6.92-7.41(9H, m)
6624-F—C6H4Me3-Me-0
isoxazol-5-yl
6633-Cl—C6H4Me3-Me-0
isoxazol-5-yl0
6644-Cl—C6H4Me3-Me-0
isoxazol-5-yl
6653-Me—C6H4Me3-Me-0
isoxazol-5-yl
6664-Me—C6H4Me3-Me-0
isoxazol-5-yl
6674-Et—C6H4Me3-Me-0
isoxazol-5-yl
6684-NO2—C6H4Me3-Me-0
isoxazol-5-yl
6693,4-Cl2—C6H3Me3-Me-0
isoxazol-5-yl
6703,5-Cl2—C6H3Me3-Me-0
isoxazol-5-yl
6713,4-Me2—C6H3Me3-Me-0
isoxazol-5-yl
6723,5-Me2—C6H3Me3-Me-0
isoxazol-5-yl
6733-PhO—C6H4Me3-Me-0
isoxazol-5-yl
6744-Cl-3-Et—C6H3Me3-Me-0
isoxazol-5-yl
6753-EtO—C6H4Me3-Me-0
isoxazol-5-yl
6763-CF3—C6H4Me3-Me-0
isoxazol-5-yl
6774-CF3—C6H4Me3-Me-0
isoxazol-5-yl
6783-i-PrO—C6H4Me3-Me-0
isoxazol-5-yl
6793-i-Pr—C6H4Me3-Me-0
isoxazol-5-yl
6804-Cl-3-Me—C6H3Me3-Me-0
isoxazol-5-yl
681Pyridin-2-ylMe3-Me-1
isoxazol-5-yl
682Pyridin-3-ylMe3-Me-1
isoxazol-5-yl
6835-Cl-Me3-Me-1
pyridin-2-ylisoxazol-5-yl
6843-Cl-Me3-Me-1
pyridin-2-ylisoxazol-5-yl
6856-Cl-Me3-Me-1
pyridin-2-ylisoxazol-5-yl
6862-Cl-Me3-Me-1
pyridin-3-ylisoxazol-5-yl
6875-CF3-Me3-Me-1Isomer A: mp 88.0-90.0° C.
pyridin-2-ylisoxazol-5-ylIsomer B: 1H-NMR(CDCl3) δ
ppm: 2.28(3H, s), 4.01(3H, s),
5.32(2H, s), 6.00(1H, s),
6.64(1H, d, J=9.2),7.22-
7.73(5H, m), 8.30(1H, d,
J=1.2)
6883-CF3-Me3-Me-1
pyridin-2-ylisoxazol-5-yl
6896-CF3-3-Cl-Me3-Me-1
pyridin-2-ylisoxazol-5-yl
6905-CF3-3-Cl-Me3-Me-1Isomer A: mp 77.0-79.0° C.
pyridin-2-ylisaxazol-5-ylIsomer B: 1H-NMR(CDCL3) δ
ppm: 2.27(3H, s), 4.03(3H, s),
5.39(2H, s), 6.02(1H, s), 7.22-
7.67(4H, m), 7.79(1H, d,
J=1.8), 8.17(1H, d, J=1.8)
691Benzothiazol-Me3-Me-1
2-ylisoxazol-5-yl
692Benzoxazol-Me3-Me-1
2-ylisoxazol-5-yl
693Quinolin-2-ylMe3-Me-1
isoxazol-5-yl
6945-CF3-1,3,4-Me3-Me-1
thiadiazol-2-ylisoxazol-5-yl
695Pyrimidin-2-ylMe3-Me-1
isoxazol-5-yl
6965-Cl-6-Me-Me3-Me-1
pyrimidin-4-ylisoxazol-5-yl
6975-Et-6-Me-Me3-Me-1
pyrimidin-4-ylisoxazol-5-yl
6986-Cl-Me3-Me-1
pyrazin-2-ylisoxazol-5-yl
6993,6-Me2-Me3-Me-1
pyrazin-2-ylisoxazol-5-yl
7005-Me-Me3-Me-1
isoxazol-3-ylisoxazol-5-yl
701C6H5Me1,3,4-Oxadiazol-2-yl1mp 88.0-89.0° C.
7022-F—C6H4Me1,3,4-Oxadiazol-2-yl
7033-F—C6H4Me1,3,4-Oxadiazol-2-yl1
7044-F—C6H4Me1,3,4-Oxadiazol-2-yl1
7052-Cl—C6H4Me1,3,4-Oxadiazol-2-yl1mp l20.0-121.0° C.
7063-Cl—C6H4Me1,3,4-Oxadiazol-2-yl1mp 97.0-98.0° C.
7074-Cl—C6H4Me1,3,4-Oxadiazol-2-yl1mp 120-122° C.
7082-Br—C6H4Me1,3,4-Oxadiazol-2-yl1
7093-Br—C6H4Me1,3,4-Oxadiazol-2-yl1
7104-Br—C6H4Me1,3,4-Oxadiazol-2-yl1
7113-I—C6H4Me1,3,4-Oxadiazol-2-yl1
7122-Me—C6H4Me1,3,4-Oxadiazol-2-yl1mp 95-96.5° C.
7133-Me—C6H4Me1,3,4-Oxadiazol-2-yl1mp 78.5-79.5° C.
7144-Me—C6H4Me1,3,4-Oxadiazol-2-yl1
7152-Et—C6H4Me1,3,4-Oxadiazol-2-yl1
7163-Et—C6H4Me1,3,4-Oxadiazol-2-yl11H-NMR(CDCl3) δ ppm:
1.14(3H, t, J=7.3), 2.56(2H, q,
J=7.3), 4.08(3H, s), 4.99(2H,
s), 6.73-7.65(8H, m), 8.43(1H, s)
7174-Et—C6H4Me1,3,4-Oxadiazol-2-yl1
7182-MeO—C6H4Me1,3,4-Oxadiazol-2-yl1mp 85.0-86.5° C.
7193-MeO—C6H4Me1,3,4-Oxadiazol-2-yl1
7204-MeO—C6H4Me1,3,4-Oxadiazol-2-yl1
7212-CF3—C6H4Me1,3,4-Oxadiazol-2-yl1
7223-CF3—C6H4Me1,3,4-Oxadiazol-2-yl11H-NMR(CDCl3) δ ppm:
4.06(3H, s), 5.03(2H, s), 6.92-
7.59(8H, m), 8.44(1H, s)
7234-CF3—C6H4Me1,3,4-Oxadiazol-2-yl1
7242,4-F2—C6H3Me1,3,4-Oxadiazol-2-yl1
7252,5-F2—C6H3Me1,3,4-Oxadiazol-2-yl1
7262,6-F2—C6H3Me1,3,4-Oxadiazol-2-yl1
7273,4-F2—C6H3Me1,3,4-Oxadiazol-2-yl1
7283,5-F2—C6H3Me1,3,4-Oxadiazol-2-yl1
7292,3-Cl2—C6H3Me1,3,4-Oxadiazol-2-yl1
7302,4-Cl2—C6H3Me1,3,4-Oxadiazol-2-yl1
7312,5-Cl2—C6H3Me1,3,4-Oxadiazol-2-yl1mp 152.0-153.0° C.
7323,4-Cl2—C6H3Me1,3,4-Oxadiazol-2-yl11H-NMR(CDCl3) δ ppm:
4.08(3H, s), 4.96(2H, s),
6.63(1H, dd, J=2.4, 8.5),
6.89(1H, d, J=3.1), 7.24-
7.57(5H, m), 8.46(1H, s)
7333,5-Cl2—C6H3Me1,3,4-Oxadiazol-2-yl1
7342,3-Me2—C6H3Me1,3,4-Oxadiazol-2-yl1
7352,4-Me2—C6H3Me1,3,4-Oxadiazol-2-yl1
7362,5-Me2—C6H3Me1,3,4-Oxadiazol-2-yl1mp 134-135° C.
7373,4-Me2—C6H3Me1,3,4-Oxadiazol-2-yl1
7383,5-Me2—C6H3Me1,3,4-Oxadiazol-2-yl1
7392-Cl-4-Me—C6H3Me1,3,4-Oxadiazol-2-yl1
7402-Cl-5-Me—C6H3Me1,3,4-Oxadiazol-2-yl1
7414-Cl-2-Me—C6H3Me1,3,4-Oxadiazol-2-yl1mp 85.5-86.5° C.
7424-Cl-3-Me—C6H3Me1,3,4-Oxadiazol-2-yl1
7433-Ph—C6H4Me1,3,4-Oxadiazol-2-yl1
7444-Ph—C6H4Me1,3,4-Oxadiazol-2-yl1
7453-i-PrO—C6H4Me1,3,4-Oxadiazol-2-yl1
7463-i-Pr—C6H4Me1,3,4-Oxadiazol-2-yl1
7474-i-Pr—C6H4Me1,3,4-Oxadiazol-2-yl1
7483-t-Bu—C6H4Me1,3,4-Oxadiazol-2-yl1
7492-MeS—C6H4Me1,3,4-Oxadiazol-2-yl1
7504-MeS—C6H4Me1,3,4-Oxadiazol-2-yl1
7512,3,6-F3—C6H2Me1,3,4-Oxadiazol-2-yl1
7522,4,5-Cl3—C6H2Me1,3,4-Oxadiazol-2-yl1
7533-PhO—C6H4Me1,3,4-Oxadiazol-2-yl1
7543,4,5-(MeO)3—C6H2Me1,3,4-Oxadiazol-2-yl1
7552,3,5-Me3—C6H2Me1,3,4-Oxadiazol-2-yl1
7563,4,5-Me3—C6H2Me1,3,4-Oxadiazol-2-yl1
757C6F5Me1,3,4-Oxadiazol-2-yl1
7584-Cl-3-Et—C6H3Me1,3,4-Oxadiazol-2-yl1
7593-EtO—C6H4Me1,3,4-Oxadiazol-2-yl1
7604-EtO—C6H4Me1,3,4-Oxadiazol-2-yl1
761C6H5Me1,3,4-Oxadiazol-2-yl0
7624-F—C6H4Me1,3,4-Oxadiazol-2-yl0
7633-Cl—C6H4Me1,3,4-Oxadiazol-2-yl0
7644-Cl—C6H4Me1,3,4-Oxadiazol-2-yl0
7653-Me—C6H4Me1,3,4-Oxadiazol-2-yl0
7664-Me—C6H4Me1,3,4-Oxadiazol-2-yl0
7674-Et—C6H4Me1,3,4-Oxadiazol-2-yl0
7684-NO2—C6H4Me1,3,4-Oxadiazol-2-yl0
7693,4-Cl2—C6H3Me1,3,4-Oxadiazol-2-yl0
7703,5-Cl2—C6H3Me1,3,4-Oxadiazol-2-yl0
7713,4-Me2—C6H3Me1,3,4-Oxadiazol-2-yl0
7723,5-Me2—C6H3Me1,3,4-Oxadiazol-2-yl0
7733-PhO—C6H4Me1,3,4-Oxadiazol-2-yl0
7744-Cl-3-Et—C6H3Me1,3,4-Oxadiazol-2-yl0
7753-EtO—C6H4Me1,3,4-Oxadiazol-2-yl0
7763-CF3—C6H4Me1,3,4-Oxadiazol-2-yl0
7774-CF3—C6H4Me1,3,4-Oxadiazol-2-yl0
7783-i-PrO—C6H4Me1,3,4-Oxadiazol-2-yl0
7793-i-Pr—C6H4Me1,3,4-Oxadiazol-2-yl0
7804Cl-3-Me—C6H3Me1,3,4-Oxadiazol-2-yl0
781Pyridin-2-ylMe1,3,4-Oxadiazol-2-yl1
782Pyridin-3-ylMe1,3,4-Oxadiazol-2-yl1
7835-Cl-Me1,3,4-Oxadiazol-2-yl1
pyridin-2-yl
7843-Cl-Me1,3,4-Oxadiazol-2-yl1
pyridin-2-yl
7856-Cl-Me1,3,4-Oxadiazol-2-yl1
pyridin-2-yl
7862-Cl-Me1,3,4-Oxadiazol-2-yl1
pyridin-3-yl
7875-CF3-Me1,3,4-Oxadiazol-2-yl1
pyridin-2-yl
7883-CF3-Me1,3,4-Oxadiazol-2-yl1
pyridin-2-yl
7896-CF3-3-Cl-Me1,3,4-Oxadiazol-2-yl1
pyridin-2-yl
7905-CF3-3-Cl-Me1,3,4-Oxadiazol-2-yl1
pyridin-2-yl
791Benzothiazol-Me1,3,4-Oxadiazol-2-yl1
2-yl
792Benzoxazol-Me1,3,4-Oxadiazol-2-yl1
-2-yl
793Quinolin-2-ylMe1,3,4-Oxadiazol-2-yl1
7945-CF3-1,3,4-Me1,3,4-Oxadiazol-2-yl1
thiadiazol-2-yl
795Pyrimidin-2-ylMe1,3,4-Oxadiazol-2-yl1
7965-Cl-6-Me-Me1,3,4-Oxadiazol-2-yl1
pyrimidin-4-ylMe
7975-Et-6-Me-Me1,3,4-Oxadiazol-2-yl1
pyrimidin-4-yl
7986-Cl-Me1,3,4-Oxadiazol-2-yl1
pyrazin-2-yl
7993,6-Me2-Me1,3,4-Oxadiazol-2-yl1
pyrazin-2-yl
8005-Me-Me1,3,4-Oxadiazol-2-yl1
isoxazol-3-yl
801C6H5Me1,2,4-Oxadiazol-3-yl1mp 70.5-71.5° C.
8022-F—C6H4Me1,2,4-Oxadiazoi-3-yl1
8033-F—C6H4Me1,2,4-Oxadiazol-3-yl1
8044-F—C6H4Me1,2,4-Oxadiazol-3-yl1
8052-Cl—C6H4Me1,2,4-Oxadiazol-3-yl1mp 139.0-140.0° C.
8063-Cl—C6H4Me1,2,4-Oxadiazol-3-yl1
8074-Cl—C6H4Me1,2,4-Oxadiazol-3-yl1mp 107-108° C.
8082-Br—C6H4Me1,2,4-Oxadiazol-3-yl1
8093-Br—C6H4Me1,2,4-Oxadiazol-3-yl1
8104-Br—C6H4Me1,2.4-Oxadiazol-3-yl1
8113-I—C6H4Me1,2,4-Oxadiazol-3-yl1
8122-Me—C6H4Me1,2,4-Oxadiazol-3-yl1mp 79-80° C.
8133-Me—C6H4Me1,2,4-Oxadiazol-3-yl1
8144-Me—C6H4Me1,2,4-Oxadiazol-3-yl1mp 92.5-93.5° C.
8152-Et—C6H4Me1,2,4-Oxadiazol-3-yl1
8163-Et—C6H4Me1,2,4-Oxadiazol-3-yl1
8174-Et—C6H4Me1,2,4-Oxadiazol-3-yl1
8182-MeO—C6H4Me1,2,4-Oxadiazol-3-yl1
8193-MeO—C6H4Me1,2,4-Oxadiazol-3-yl1
8204-MeO—C6H4Me1,2,4-Oxadiazol-3-yl1
8212-CF3—C6H4Me1,2,4-Oxadiazol-3-yl1
8223-CF3—C6H4Me1,2,4-Oxadiazol-3-yl1
8234-CF3—C6H4Me1,2,4-Oxadiazol-3-yl1
8242,4-F2—C6H3Me1,2,4-Oxadiazol-3-yl1
8252,5-F2—C6H3Me1,2,4-Oxadiazol-3-yl1
8262,6-F2—C6H3Me1,2,4-Oxadiazol-3-yl1
8273,4-F2—C6H3Me1,2,4-Oxadiazol-3-yl1
8283,5-F2—C6H3Me1,2,4-Oxadiazol-3-yl1
8292,3-Cl2—C6H3Me1 ,2,4-Oxadiazol-3-yl1
8302,4-Cl2—C6H3Me1,2,4-Oxadiazol-3-yl1
8312,5-Cl2—C6H3Me1,2,4-Oxadiazol-3-yl1
8323,4-Cl2—C6H3Me1,2,4-Oxadiazol-3-yl1
8333,5-Cl2—C6H3Me1,2,4-Oxadiazol-3-yl1
8342,3-Me2—C6H3Me1,2,4-Oxadiazol-3-yl1
8352,4-Me2—C6H3Me1,2,4-Oxadiazol-3-yl1
8362,5-Me2—C6H3Me1,2,4-Oxadiazol-3-yl1Isomer A: mp 116.5-117.5° C.
Isomer B: mp 69-71° C.
8373,4-Me2—C6H3Me1,2,4-Oxadiazol-3-yl1
8383,5-Me2—C6H3Me1,2,4-Oxadiazol-3-yl1
8392-Cl-4-Me—C6H3Me1,2,4-Oxadiazol-3-yl1
8402-Cl-5-Me—C6H3Me1,2,4-Oxadiazol-3-yl1
8414-Cl-2-Me—C6H3Me1,2,4-Oxadiazol-3-yl1mp 127-128° C.
8424-Cl-3-Me—C6H3Me1,2,4-Oxadiazol-3-yl1
8433-Ph—C6H4Me1,2,4-Oxadiazol-3-yl1
8444-Ph—C6H4Me1,2,4-Oxadiazol-3-yl1mp 147.5-148.5° C.
8453-i-PrO—C6H4Me1,2,4-Oxadiazol-3-yl1
8463-i-Pr—C6H4Me1,2,4-Oxadiazol-3-yl1
8474-i-Pr—C6H4Me1,2,4-Oxadiazol-3-yl1
8483-t-Bu—C6H4Me1,2,4-Oxadiazol-3-yl1
8492-MeS—C6H4Me1,2,4-Oxadiazol-3-yl1
8504-MeS—C6H4Me1,2,4-Oxadiazal-3-yl1
8512,3,6-F3—C6H2Me1,2,4-Oxadiazol-3-yl1
8522,4,5-Cl3—C6H2Me1,2,4-Oxadiazol-3-yl1
8533-PhO—C6H4Me1,2,4-Oxadiazol-3-yl1
8543,4,5-(MeO)3—C6H2Me1,2,4-Oxadiazol-3-yl1
8552,3,5-Me3—C6H2Me1,2,4-Oxadiazol-3-yl1
8563,4,5-Me3—C6H2Me1,2,4-Oxadiazol-3-yl1
857C6F5Me1,2,4-Oxadiazol-3-yl1
8584-Cl-3-Et—C6H3Me1,2,4-Oxadiazol-3-yl1
8593-EtO—C6H4Me1,2,4-Oxadiazol-3-yl1
8604-EtO—C6H4Me1,2,4-Oxadiazol-3-yl1
861C6H5Me1,2,4-Oxadiazol-3-yl0
8624-F—C6H4Me1,2,4-Oxadiazol-3-yl0
8633-Cl—C6H4Me1,2,4-Oxadiazol-3-yl0
8644-Cl—C6H4Me1,2,4-Oxadiazol-3-yl0
8653-Me—C6H4Me1,2,4-Oxadiazol-3-yl0
8664-Me—C6H4Me1,2,4-Oxadiazol-3-yl0
8674-Et—C6H4Me1,2,4-Oxadiazol-3-yl0
8684-NO2—C6H4Me1,2,4-Oxadiazol-3-yl0
8693,4-Cl2—C6H3Me1,2,4-Oxadiazol-3-yl0
8703,5-Cl2—C6H3Me1,2,4-Oxadiazol-3-yl0
8713,4-Me2—C6H3Me1,2,4-Oxadiazol-3-yl0
8723,5-Me2—C6H3Me1,2,4-Oxadiazol-3-yl0
8733-PhO—C6H4Me1,2,4-Oxadiazol-3-yl0
8744-Cl-3-Et—C6H3Me1,2,4-Oxadiazol-3-yl0
8753-EtO—C6H4Me1,2,4-Oxadiazol-3-yl0
8763-CF3—C6H4Me1,2,4-Oxadiazol-3-yl0
8774-CF3—C6H4Me1,2,4-Oxadiazol-3-yl0
8783-i-PrO—C6H4Me1,2,4-Oxadiazol-3-yl0
8793-i-Pr—C6H4Me1,2,4-Oxadiazol-3-yl0
8804-Cl-3-Me—C6H3Me1,2,4-Oxadiazol-3-yl0
881Pyridin-2-ylMe1,2,4-Oxadiazol-3-yl1
882Pyridin-3-ylMe1,2,4-Oxadiazol-3-yl1
8835-Cl-Me1,2,4-Oxadiazol-3-yl1
pyridin-2-yl
8843-Cl-Me1,2,4-Oxadiazol-3-yl1
pyridin-2-yl
8856-Cl-Me1,2,4-Oxadiazol-3-yl1
pyridin-2-yl
8862-Cl-Me1,2,4-Oxadiazol-3-yl1mp 177-178.5° C.
pyridin-3-yl
8875-CF3-Me1,2,4-Oxadiazol-3-yl1
pyridin-2-yl
8883-CF3-Me1,2,4-Oxadiazol-3-yl1
pyridin-2-yl
8896-CF3-3-Cl-Me1,2,4-Oxadiazol-3-yl1
pyridin-2-yl
8905-CF3-3-Cl-Me1,2,4-Oxadiazol-3-yl1
pyridin-2-yl
891Benzothiazol-Me1,2,4-Oxadiazol-3-yl1
2-yl
892Benzoxazol-Me1,2,4-Oxadiazol-3-yl1
2-yl
893Quinolin-2-ylMe1,2,4-Oxadiazol-3-yl1
8945-CF3-1,3,4-Me1,2,4-Oxadiazol-3-yl1
thiadiazol-2-yl
895Pyrimidin-2-ylMe1,2,4-Oxadiazol-3-yl1
8965-Cl-6-Me-Me1,2,4-Qxadiazol-3-yl1
pyrimidin-4-yl
8975-Et-6-Me-Me1,2,4-Oxadiazol-3-yl1
pyrimidin-4-yl
8986-Cl-Me1,2,4-Oxadiazol-3-yl1
pyrazin-2-yl
8993,6-Me2-Me1,2,4-Oxadiazol-3-yl1
pyrazin-2-yl
9005-Me-Me1,2,4-Oxadiazol-3-yl1
isoxazol-3-yl
901C6H5Me5-Me-1,2,4-11H-NMR(CDCl3) δ ppm:
oxadiazol-3-yl2.64(3H, s), 4.07(3H, s),
4.98(2H, s), 6.82-6.94(2H, m),
7.18-7.63(7H, m)
9022-F—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9033-F—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9044-F—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9052-Cl—C6H4Me5-Me-1,2,4-1mp 88.5-89.5° C.
oxadiazol-3-yl
9063-Cl—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9074-Cl—C6H4Me5-Me-1,2,4-1mp 125-126° C.
oxadiazol-3-yl
9082-Br—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9093-Br—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9104-Br—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9113-I—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9122-Me—C6H4Me5-Me-1,2,4-1mp 86-87.5° C.
oxadiazol-3-yl
9133-Me—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9144-Me—C6H4Me5-Me-1,2,4-1mp 92.5-93.5° C.
oxadiazol-3-yl
9152-Et—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9163-Et—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9174-Et—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9182-MeO—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9193-MeO—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9204-MeO—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9212-CF3—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9223-CF3—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9234-CF3—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9242,4-F2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9252,5-F2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9262,6-F2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9273,4-F2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9283,5-F2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9292,3-Cl2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9302,4-Cl2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9312,5-Cl2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9323,4-Cl2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9333,5-Cl2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9342,3-Me2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9352,4-Me2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9362,5-Me2—C6H3Me5-Me-1,2,4-1Isomer A mp 98-100° C.
oxadiazol-3-ylIsomer B mp 130-131.5° C.
9373,4-Me2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9383,5-Me2—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9392-Cl-4-Me—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9402-Cl-5-Me—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9414-Cl-2-Me—C6H3Me5-Me-1,2,4-1mp 115-116° C.
oxadiazol-3-yl
9424-Cl-3-Me—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9433-Ph—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9444-Ph—C6H4Me5-Me-1,2,4-1mp 124.5-125.5° C.
oxadiazol-3-yl
9453-i-PrO—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9463-i-Pr—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9474-i-Pr—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9483-t-Bu—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9492-MeS—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9504-MeS—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9512,3,6-F3—C6H2Me5-Me-1,2,4-1
oxadiazol-3-yl
9522,4,5-Cl3—C6H2Me5-Me-1,2,4-1
oxadiazol-3-yl
9533-PhO—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9543,4,5-(MeO)3—C6H2Me5-Me-1,2,4-1
oxadiazol-3-yl
9552,3,5-Me3—C6H2Me5-Me-1,2,4-1
oxadiazol-3-yl
9563,4,5-Me3—C6H2Me5-Me-1,2,4-1
oxadiazol-3-yl
957C6F5Me5-Me-1,2.4-1
oxadiazol-3-yl
9584-Cl-3-Et—C6H3Me5-Me-1,2,4-1
oxadiazol-3-yl
9593-EtO—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
9604-EtO—C6H4Me5-Me-1,2,4-1
oxadiazol-3-yl
961C6H5Me5-Me-1,2,4-0
oxadiazol-3-yl
9624-F—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9633-Cl—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9644-Cl—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9653-Me—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9664-Me—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9674-Et—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9684-NO2—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9693,4-Cl2—C6H3Me5-Me-1,2,4-0
oxadiazol-3-yl
9703,5-Cl2—C6H3Me5-Me-1,2,4-0
oxadiazol-3-yl
9713,4-Me—C6H3Me5-Me-1,2,4-0
oxadiazol-3-yl
9723,5-Me—C6H3Me5-Me-1,2,4-0
oxadiazol-3-yl
9733-PhO—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9744-Cl-3-Et—C6H3Me5-Me-1,2,4-0
oxadiazol-3-yl
9753-EtO—C6H4Me5-Me-1,2.4-0
oxadiazol-3-yl
9763-CF3—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9774-CF3—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9783-i-PrO—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9793-i-Pr—C6H4Me5-Me-1,2,4-0
oxadiazol-3-yl
9804-Cl-3-Me—C6H3Me5-Me-1,2,4-0
oxadiazol-3-yl
981Pyridin-2-ylMe5-Me-1,2,4-1
oxadiazol-3-yl
982Pyridin-3-ylMe5-Me-1,2,4-1
oxadiazol-3-yl
9835-Cl-Me5-Me-1,2,4-1
pyridin-2-yloxadiazol-3-yl
9843-Cl-Me5-Me-1,2,4-1
pyridin-2-yloxadiazol-3-yl
9856-Cl-Me5-Me-1,2,4-1
pyridin-2-yloxadiazol-3-yl
9862-Cl-Me5-Me-1,2,4-1mp 82.5-84.5° C.
pyridin-3-yloxadiazol-3-yl
9875-CF3-Me5-Me-1,2,4-1
pyridin-2-yloxadiazol-3-yl
9883-CF3-Me5-Me-1,2,4-1
pyridin-2-yloxadiazol-3-yl
9896-CF3-3-Cl-Me5-Me-1,2,4-1
pyridin-2-yloxadiazol-3-yl
9905-CF3-3-Cl-Me5-Me-1,2,4-1
pyridin-2-yloxadiazol-3-yl
991Benzothiazol-Me5-Me-1,2,4-1
2-yloxadiazol-3-yl
992Benzoxazol-Me5-Me-1,2,4-1
2-yloxadiazol-3-yl
993Quinolin-2-ylMe5-Me-1,2,4-1
oxadiazol-3-yl
9945-CF3-1,3,4-Me5-Me-1,2,4-1
thiadiazol-2-yloxadiazol-3-yl
995Pyrimidin-2-ylMe5-Me-1,2,4-1
oxadiazol-3-yl
9965-Cl-6-Me-Me5-Me-1,2,4-1
pyrimidin-4-yloxadiazol-3-yl
9975-Et-6-Me-Me5-Me-1,2,4-1
pyrimidin-4-yloxadiazol-3-yl
9986-Cl-Me5-Me-1,2,4-1
pyrazin-2-yloxadiazol-3-yl
9993,6-Me2-Me5-Me-1,2,4-1
pyrazin-2-yloxadiazol-3-yl
10005-Me-Me5-Me-1,2,4-1
isoxazol-3-yloxadiazol-3-yl
1001C6H5Me1-Me-1H-1mp 83.0-84.5° C.
tetrazol-5-yl
10022-F-C6H4Me1-Me-1H-1
tetrazol-5-yi
10033-F—C6H4Me1-Me-1H-1
tetrazol-5-yl
10044-F—C6H4Me1-Me-1H-1
tetrazoi-5-yl
10052-Cl—C6H4Me1-Me-1H-1mp 118-119° C.
tetrazol-5-yl
10063-Cl—C6H4Me1-Me-1H-1
tetrazol-5-yl
10074-Cl—C6H4Mei-Me-1H-1mp 95-96° C.
tetrazol-5-yl
10082-Br—C6H4Me1-Me-1H-1
tetrazol-5-yl
10093-Br—C6H4Me1-Me-1H-1
tetrazol-5-yl
10104-Br—C6H4Me1-Me-1H-1
tetrazol-5-yl
10113-I-C6H4Me1-Me-1H-1
tetrazol-5-yl
10122-Me—C6H4Me1-Me-1H-1mp 111-112° C.
tetrazol-5-yl
10133-Me—C6H4Me1-Me-1H-1
tetrazol-5-yl
10144-Me—C6H4Me1-Me-1H-1mp 138.5-139.5° C.
tetrazol-5-yl
10152-Et—C6H4Me1-Me-1H-1
tetrazol-5-yl
10163-Et—C6H4Me1-Me-1H-1
tetrazol-5-yl
10174-Et—C6H4Me1-Me-1H-1
tetrazol-5-yl
10182-MeO—C6H4Me1-Me-1H-1
tetrazol-5-yl
10193-MeO—C6H4Me1-Me-1H-1
tetrazol-5-yl
10204-MeO—C6H4Me1-Me-1H-1
tetrazol-5-yl
10212-CF3—C6H4Me1-Me-1H-1
tetrazol-5-yl1
10223-CF3—C6H4Me1-Me-1H-11H-NMR(CDCl3) δ ppm:
tetrazol-5-yl4.03(3H, s), 4.21(3H, s),
4.99(2H, s), 6.82-7.53(8H, m)
10234-CF3—C6H4Me1-Me-1H-1
tetrazol-5-yl
10242,4-F2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10252,5-F2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10262,6-F2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10273,4-F2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10283,5-F2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10292,3-Cl2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10302,4-Cl2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10312,5-Cl2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10323,4-Cl2—C6H3Me1-Me-1H-1mp 127-127.5° C.
tetrazol-5-yl
10333,5-Cl2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10342,3-Me2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10352,4-Me2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10362,5-Me2—C6H3Me1-Me-1H-1mp 115.5p14 116.5° C.
tetrazol-5-yl
10373,4-Me2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10383,5-Me2—C6H3Me1-Me-1H-1
tetrazol-5-yl
10392-Cl-4-Me—C6H3Me1-Me-1H-1
tetrazol-5-yl
10402-Cl-5-Me—C6H3Me1-Me-1H-1
tetrazol-5-yl
10414-Cl-2-Me—C6H3Me1-Me-1H-1mp 126.5-127.5° C.
tetrazol-5-yl
10424-Cl-3-Me—C6H3Me1-Me-1H-1
tetrazol-5-yl
10433-Ph—C6H4Me1-Me-1H-1
tetrazol-5-yl
10444-Ph—C6H4Me1-Me-1H-1mp 130.5-131.5° C.
tetrazol-5-yl
10453-i-PrO—C6H4Me1-Me-1H-1
tetrazol-5-yl
10463-i-Pr—C6H4Me1-Me-1H-1
tetrazol-5-yl
10474-i-Pr—C6H4Me1-Me-1H-1
tetrazol-5-yl
10483-t-Bu—C6H4Me1-Me-1H-1
tetrazol-5-yl
10492-MeS—C6H4Me1-Me-1H-1
tetrazol-5-yl
10504-MeS—C6H4Me1-Me-1H-1
tetrazol-5-yl
10512,3,6-F3—C6H2Me1-Me-1H-1
tetrazol-5-yl
10522,4,5-Cl3—C6H2Me1-Me-1H-1
tetrazol-5-yl
10533-PhO—C6H4Me1-Me-1H-1
tetrazol-5-yl
10543,4,5-(MeO)3—C6H2Me1-Me-1H-1
tetrazol-5-yl
10552,3,5-Me3—C6H2Me1-Me-1H-1
tetrazol-5-yl
10563,4,5-Me3—C6H2Me1-Me-1H-1
tetrazol-5-yl
1057C6F5Me1-Me-1H-1
tetrazol-5-yl
10584-Cl-3-Et—C6H3Me1-Me-1H-1
tetrazol-5-yl
10593-EtO—C6H4Me1-Me-1H-1
tetrazol-5-yl
10604-EtO—C6H4Me1-Me-1H-1
tetrazol-5-yl
1061C6H5Me1-Me-1H-0
tetrazol-5-yl
10624-F—C6H4Me1-Me-1H-0
tetrazol-5-yl
10633-Cl—C6H4Me1-Me-1H-0
tetrazol-5-yl
10644-Cl—C6H4Me1-Me-1H-0
tetrazol-5-yl
10653-Me—C6H4Me1-Me-1H-0
tetrazol-5-yl
10664-Me—C6H4Me1-Me-1H-0
tetrazol-5-yl
10674-Et—C6H4Me1-Me-1H-0
tetrazol-5-yl
10684-NO2—C6H4Me1-Me-1H-0
tetrazol-5-yl
10693,4-Cl2—C6H3Me1-Me-1H-0
tetrazol-5-yl
10703,5-Cl2—C6H3Me1-Me-1H-0
tetrazol-5-yl
10713,4-Me2—C6H3Me1-Me-1H-0
tetrazol-5-yl
10723,5-Me2—C6H3Me1-Me-1H-0
tetrazol-5-yl
10733-PhO—C6H4Me1-Me-1H-0
tetrazol-5-yl
10744-Cl-3-Et—C6H3Me1-Me-1H-0
tetrazol-5-yl
10753-EtO—C6H4Me1-Me-1H-0
tetrazol-5-yl
10763-CF3—C6H4Me1-Me-1H-0
tetrazol-5-yl
10774-CF3—C6H4Me1-Me-1H-0
tetrazol-5-yl
10783-i-PrO—C6H4Me1-Me-1H-0
tetrazol-5-yl
10793-i-Pr—C6H4Me1-Me-1H-0
tetrazol-5-yl
10804-Cl-3-Me—C6H3Me1-Me-1H-0
tetrazol-5-yl
1081Pyridin-2-ylMe1-Me-1H-1
tetrazol-5-yl
1082Pyridin-3-ylMe1-Me-1H-1
tetrazol-5-yl
10835-Cl-Me1-Me-1H-1
pyridin-2-yltetrazol-5-yl
10843-Cl-Me1-Me-1H-1
pyridin-2-yltetrazol-5-yl
10856-Cl-Me1-Me-1H-1
pyridin-2-yltetrazol-5-yl
10862-Cl-Me1-Me-1H-1
pyridin-3-yltetrazol-5-yl
10875-CF3-Me1-Me-1H-1
pyridin-2-yltetrazol-5-yl
10883-CF3-Me1-Me-1H-1
pyridin-2-yltetrazol-5-yl
10896-CF3-3-Cl-Me1-Me-1H-1
pyridin-2-yltetrazol-5-yl
10905-CF3-3-Cl-Me1-Me-1H-1
pyridin-2-yltetrazol-5-yl
1091Benzothiazol-Me1-Me-1H-1
2-yltetrazol-5-yl
1092Benzoxazol-Me1-Me-1H-1
2-yltetrazol-5-yl
1093Quinolin-2-ylMe1-Me-1H-1
tetrazol-5-yl
10945-CF3-1,3,4-Me1-Me-1H-1
thiadiazol-2-yltetrazol-5-yl
1095Pyrimidin-2-ylMe1-Me-1H-1
tetrazol-5-yl
10965-Cl-6-Me-Me1-Me-1H-1
pyrimidin-4-yltetrazol-5-yl
10975-Et-6-Me-Me1-Me-1H-1
pyrimidin-4-yltetrazol-5-yl
10986-Cl-Me1-Me-1H-1
pyrazin-2-yltetrazol-5-yl
10993,6-Me2-Me1-Me-1H-1
pyrazin-2-yltetrazol-5-yl
11005-Me-Me1-Me-1H-1
isoxazol-3-yltetrazol-5-yl
1101C6H5Me1-Me-2-11H-NMR(CDCl3) δ ppm: 2.75(3H, s),
imidazolin-2-yl3.40(2H, t, J=9.8), 3.92(2H, t, J=9.8),
3.97(3H, s), 5.37(2H, s), 6.93-6.98(3H,
m), 7.25-7.35(3H, m), 7.40(1H, t, J=7.5),
7.52(1H, d, J=7.5), 7.68(1H, d, J=7.5)
11022-F—C6H4Me1-Me-2-1
imidazolin-2-yl
11033-F—C6H4Me1-Me-2-1
imidazolin-2-yl
11044-F—C6H4Me1-Me-2-1
imidazolin-2-yl
11052-CF3—C6H4Me1-Me-2-1
imidazolin-2-yl
11063-CF3—C6H4Me1-Me-2-1
imidazolin-2-yl
11074-CF3—C6H4Me1-Me-2-1
imidazolin-2-yl
11082-Br—C6H4Me1-Me-2-1
imidazolin-2-yl
11093-Br—C6H4Me1-Me-2-1
imidazolin-2-yl
11104-Br—C6H4Me1-Me-2-1
imidazolin-2-yl
11113-I—6H4Me1-Me-2-1
imidazolin-2-yl
11122-Me—C6H4Me1-Me-2-11H-NMR(CDCl3) δ ppm: 2.33(3H, s),
imidazolin-2-yl2.74(3H, s), 3.40(2H, t, J=9.8), 3.93(2H,
t, J=9.8), 4.02(3H, s), 5.38(2H, s), 6.82-
6.88(2H, m), 7.31-7.35(2H, m), 7.33(1H,
t, J=7.7), 7.41(1H, t, J=7.7), 7.51(1H, d,
J=7.7), 7.76(1H, d, J=7.7)
11133-Me—C6H4Me1-Me-2-11H-NMR(CDCl3) δ ppm: 2.32(3H, s),
imidazolin-2-yl2.75(3H, s), 3.40(2H, t, J=9.8), 3.92(2H,
t, J=9.8), 3.90(3H, s), 5.35(2H, s), 6.75-
6.80(3H, m), 7.16(1H, t, J=7.6), 7.30-
7.43(2H, m), 7.51(1H, dd, J=7.6, 1.5),
7.68(1H, d, J=7.6)
11144-Me—C6H4Me1-Me-2-11H-NMR(CDCl3) δ ppm: 2.28(3H, s),
imidazolin-2-yl2.75(3H, s), 3.40(2H, t, J=9.8), 3.92(2H,
t, J=9.8), 3.98(3H, s), 5.34(2H, s),
6.85(2H, d, J=8.5), 7.07(2H, d, J=8.5),
7.29-7.42(2H, m), 7.51(1H, dd, J=7.6,
1.5), 7.67(1H, d, J=7.6)
11152-Et—C6H4Me1-Me-2-1
imidazolin-2-yl
11163-Et—C6H4Me1-Me-2-1
imidazolin-2-yl
11174-Et—C6H4Me1-Me-2-1
imidazolin-2-yl
11182-MeO—C6H4Me1-Me-2-1
imidazolin-2-yl
11193-MeO—C6H4Me1-Me-2-1
imidazolin-2-yl
11204-MeO—C6H4Me1-Me-2-1
imidazolin-2-yl
11212-Cl—C6H4Me1-Me-2-11H-NMR(CDCl3) δ ppm: 2.75(3H, s),
imidazolin-2-yl3.41 (2H, t, J=9.8), 3.93(2H, t, J=9.8),
4.02(3H, s), 5.47(2H, s), 6.86-6.93(2H, m),
7.18(1H, ddd, J=8.5, 7.6, 1.5), 7.31-
7.45(3H, m), 7.49(1H, dd, J=7.6, 1.5),
7.81(1H, d, J=7.6)
11223-Cl—C6H4Me1-Me-2-1Isomer A 1H-NMR(CDCl3) δ ppm: 2.75(3H,
imidazolin-2-yls), 3.41 (2H, t, J=9.8), 3.92(2H, t, J=9.8),
3.97(3H, s), 5.35(2H, s), 6.84-6.99(3H, m),
7.19(1H, t, J=8.0), 7.32-7.44(2H, m),
7.51(1H, dd, J=7.3, 1.4), 7.64(1H, d,
J=7.0)
Isomer B 1H-NMR(CDCl3) δ ppm: 3.03(3H,
s), 3.38(2H, t, J=9.9), 3.77(2H, t, J=9.9),
3.97(3H, s), 4.99(2H, s), 6.83-7.16(4H, m),
7.23(1H, d, J=7.6), 7.34-7.39(2H, m),
7.49(1H, d, J=6.4)
11234-Cl—C6H4Me1-Me-2-1mp 53-56° C.
imidazolin-2-yl
11242,4-F2—C6H3Me1-Me-2-1
imidazolin-2-yl
11252,5-F2—C6H3Me1-Me-2-1
imidazolin-2-yl
11262,6-F2—C6H3Me1-Me-2-1
imidazolin-2-yl
11273,4-F2—C6H3Me1-Me-2-1
imidazolin-2-yl
11283,5-F2—C6H3Me1-Me-2-1
imidazolin-2-yl
11292,3-Cl2—C6H3Me1-Me-2-1
imidazolin-2-yl
11302,4-Cl2—C6H3Me1-Me-2-1
imidazolin-2-yl
11312,5-Cl2—C6H3Me1-Me-2-1
imidazolin-2-yl
11323,4-Cl2—C6H3Me1-Me-2-1
imidazolin-2-yl
11333,5-Cl2—C6H3Me1-Me-2-1
imidazolin-2-yl
11342,3-Me2—C6H3Me1-Me-2-1
imidazolin-2-yl
11352,4-Me2—C6H3Me1-Me-2-1
imidazolin-2-yl
11362,5-Me2—C6H3Me1-Me-2-1mp 88-90° C.
imidazolin-2-yl
11373,4-Me2—C6H3Me1-Me-2-1
imidazolin-2-yl
11383,5-Me2—C6H3Me1-Me-2-1
imidazolin-2-yl
11392-C1-4-Me—C6H3Me1-Me-2-1
imidazolin-2-yl
11402-Cl-5-Me—C6H3Me1-Me-2-1
imidazolin-2-yl
11414-Cl-2-Me—C6H3Me1-Me-2-imidazolin-1
2-yl
11424-Cl-4-Me—C6H3Me1-Me-2-imidazolin1
2-yl
11433-Ph—C6H4Me1-Me-2-imidazolin-1
2-yl
11444-Ph—C6H4Me1-Me-2-imidazolin-1
2-yl
11453-i-PrO—6H4Me1-Me-2-imidazolin-1
2-yl
11463-i-Pr—C6H4Me1-Me-2-imidazolin-1
2-yl
11474-i-Pr—C6H4Me1-Me-2-imidazolin-1
2-yl
11483-t-Bu—C6H4Me1-Me-2-imidazolin-1
2-yl
11492-MeS—C6H4Me1-Me-2-imidazolin-1
2-yl
11504-MeS—C6H4Me1-Me-2-imidazolin-1
2-yl
11512,3,6-F3—C6H2Me1-Me-2-imidazolin-1
2-yl
11522,4,5-Cl3—C6H2Me1-Me-2-imidazolin-1
2-yl
11533-PhO—C6H4Me1-Me-2-imidazolin-1
2-yl
11543,4,5-(MeO)3—C6H2Me1-Me-2-imidazolin-1
2-yl
11552,3,5-Me3—C6H2Me1-Me-2-imidazolin-1
2-yl
11562,3,5-Me3—C6H2Me1-Me-2-imidazolin-1
2-yl
1157C6F5Me1-Me-2-imidazolin-1
2-yl
11584-Cl-3-Et—C6H3Me1-Me-2-imidazolin-1
2-yl
11593-EtO—C6H4Me1-Me-2-imidazolin-1
2-yl
11604-EtO—C6H4Me1-Me-2-imidazolin-1
2-yl
1161C6H5Me1-Me-2-imidazolin-01H-NMR(CDCl3) δ ppm:
2-yl2.80(2.91 )(3H, s),
3.03(3.14)(2H, s),
3.53(3.61)(2H, t, J=9.8),
4.05(3.95)(3H, s), 6.96-
7.72(9H, m)
11624-F—C6H4Me1-Me-2-imidazolin-0
2-yl
11633-Cl—C6H4Me1-Me-2-imidazolin-0
2-yl
11644-Cl—C6H4Me1-Me-2-imidazolin-0
2-yl
11653-Me—C6H4Me1-Me-2-imidazolin-0
2-yl
11664-Me—C6H4Me1-Me-2-imidazolin-0
2-yl
11674-Et—C6H4Me1-Me-2-imidazolin-0
2-yl
11684-NO2—C6H4Me1-Me-2-imidazolin-0
2-yl
11693,4-Cl2—C6H3Me1-Me-2-imidazolin-0
2-yl
11703,5-Cl2—C6H3Me1-Me-2-imidazolin-0
2-yl
11713,4-Me2—C6H3Me1-Me-2-imidazolin-0
2-yl
11723,5-Me2—C6H3Me1-Me-2-imidazolin-0
2-yl
11733-PhO—C6H4Me1-Me-2-imidazolin-0
2-yl
11744-Cl-3-Et—C6H3Me1-Me-2-imidazolin-0
2-yl
11753-EtO—C6H4Me1-Me-2-imidazolin-0
2-yl
11763-CF3—C6H4Me1-Me-2-imidazolin-0
2-yl
11774-CF3—C6H4Me1-Me-2-imidazolin-0
2-yl
11783-i-PrO—C6H4Me1-Me-2-imidazolin-0
2-yl
11793-i-Pr—C6H4Me1-Me-2-imidazolin-0
2-yl
11804-Cl-3-Me—C6H3Me1-Me-2-imidazolin-0
2-yl
1181Pyridin-2-ylMe1-Me-2-imidazolin-1
2-yl
1182Pyridin-3-ylMe1-Me-2-imidazolin1
2-yl
11835-Cl-Me1-Me-2-imidazolin-1
pyridin-2-yl2-yl
11843-Cl-Me1-Me-2-imidazolin-1
pyridin-2-yl2-yl
11856-Cl-Me1-Me-2-imidazolin-1
pyridin-2-yl2-yl
11862-Cl-Me1-Me-2-imidazolin-1
pyridin-3-yl2-yl
11875-CF3-Me1-Me-2-imidazolin-1
pyridin-2-yl2-yl
11883-CF3-Me1-Me-2-imidazolin-1
pyridin-2-yl2-yl
11896-CF3-3-Cl-Me1-Me-2-imidazolin-1
pyridin-2-yl2-yl
11905-CF3-3-Cl-Me1-Me-2-imidazolin-1
pyridin-2-yl2-yl
1191Benzothiazol-Me1-Me-2-imidazolin-1
-2-yl2-yl
1192Benzoxazol-Me1-Me-2-imidazolin-1
-2-yl2-yl
1193Quinolin-2-ylMe1-Me-2-imidazolin-1
2-yl
11945-CF3-1,3,4-Me1-Me-2-imidazolin-1
thiadiazol-2-yl2-yl
1195Pyrimidin-2-ylMe1-Me-2-imidazolin-1
2-yl
11965-Cl-6-Me-Me1-Me-2-imidazolin-1
pyrimidin-4-yl2-yl
11975-Et-6-Me-Me1-Me-2-imidazolin-1
pyrimidin-4-yl2-yl
11986-Cl-Me1-Me-2-imidazolin-1
pyrazin-2-yl2-yl
11993,6-Me2-Me1-Me-2-imidazolin-1
pyrazin-2-yl2-yl
12005-Me-Me1-Me-2-imidazolin-1
isoxazol-3-yl2-yl
1201C6H5Me2-Isoxazolin-3-yl1
12022-F—C6H4Me2-Isoxazolin-3-yl1
12033-F—C6H4Me2-Isoxazolin-3-yl1
12044-F—C6H4Me2-Isoxazolin-3-yl1
12052-Cl—C6H4Me2-Isoxazolin-3-yl1
12063-Cl—C6H4Me2-Isoxazolin-3-yl1
12074-Cl—C6H4Me2-Isoxazolin-3-yl1
12082-Br—C6H4Me2-Isoxazolin-3-yl1
12093-Br—C6H4Me2-Isoxazolin-3-yl1
12104-Br—C6H4Me2-Isoxazolin-3-yl1
12113-I—C6H4Me2-isoxazolin-3-yl1
12122-Me—C6H4Me2-Isoxazolin-3-yl1
12133-Me—C6H4Me2-Isoxazolin-3-yl1
12144-Me—C6H4Me2-Isoxazolin-3-yl1
12152-Et—C6H4Me2-Isoxazolin-3-yl1
12163-Et—C6H4Me2-Isoxazolin-3-yl1
12174-Et—C6H4Me2-Isoxazolin-3-yl1
12182-MeO—C6H4Me2-Isoxazolin-3-yl1
12193-MeO—C6H4Me2-Isoxazolin-3-yl1
12204-MeO—C6H4Me2-Isoxazolin-3-yl1
12212-CF3—C6H4Me2-Isoxazolin-3-yl1
12223-CF3—C6H4Me2-Isoxazolin-3-yl1
12234-CF3—C6H4Me2-Isoxazolin-3-yl1
12242,4-F2—C6H3Me2-Isoxazolin-3-yl1
12252,5-F2—C6H3Me2-Isoxazolin-3-yl1
12262,6-F2—6H3Me2-Isoxazolin-3-yl1
12273,4-F2—C6H3Me2-Isoxazolin-3-yl1
12283,5-F2—C6H3Me2-Isoxazolin-3-yl1
12292,3-Cl2—C6H3Me2-Isaxazolin-3-yl1
12302,4-Cl2—C6H3Me2-Isoxazolin-3-yl1
12312,5-Cl2—C6H3Me2-Isoxazolin-3-yl1
12323,4-Cl2—C6H3Me2-Isoxazolin-3-yl1
12333,5-Cl2—C6H3Me2-Isoxazolin-3-yl1
12342,3-Me2—C6H3Me2-Isoxazolin-3-yl 1
12352,4-Me2—C6H3Me2-Isoxazolin-3-yl1
12362,5-Me2—C6H3Me2-Isoxazolin-3-yl12.17-2.29(6H, m), 3.24-
3.38(2H, m), 3.95(4.00)(3H, s),
4.28(4.44)(2H, t, J=10.4),
4.93-5.06(2H, m), 6.59-
7.58(7H, m)
12373,4-Me2—C5H3Me2-Isoxazolin-3-yl1
12383,5-Me2—C6H3Me2-Isoxazolin-3-yl1
12392-Cl-4-Me—C6H3Me2-Isoxazolin-3-yl1
12402-Cl-5-Me—C6H3Me2-Isoxazolin-3-yl1
12414-Cl-2-Me—C6H3Me2-Isoxazolin-3-yl1
12424-Cl-3-Me—C6H3Me2-Isoxazolin-3-yl1
12433-Ph—C6H4Me2-Isoxazolin-3-yl1
12444-Ph—C6H4Me2-Isoxazolin-3-yl1
12453-i-PrO—C6H4Me2-Isoxazolin-3-yl1
12463-i-Pr—C6H4Me2-Isaxazolin-3-yl1
12474-i-Pr—C6H4Me2-Isoxazolin-3-yl1
12483-t-Bu—C6H4Me2-Isoxazolin-3-yl1
12492-MeS—C6H4Me2-Isoxazolin-3-yl1
12504-MeS—C6H4Me2-Isoxazolin-3-yl1
12512,3,6-F3—C6H2Me2-Isoxazolin-3-yl1
12522,4,5-Cl3—C6H2Me2-Isoxazolin-3-yl1
12533-PhO—C6H4Me2-Isoxazolin-3-yl1
12543,4,5-(MeO)3—C6H2Me2-Isoxazolin-3-yl1
12552,3,5-Me3—C6H2Me2-Isoxazolin-3-yl1
12563,4,5-Me3—C6H2Me2-Isoxazolin-3-yl1
1257C6F5Me2-Isoxazolin-3-yl1
12584-Cl-3-Et—C6H3Me2-Isoxazolin-3-yl1
12593-EtO-C6H4Me2-Isoxazolin-3-yl1
12604-EtO—C6H4Me2-Isoxazolin-3-yl1
1261C6H5Me2-Isoxazolin-3-yl0
12624-F—C6H4Me2-Isoxazolin-3-yl0
12633-Cl—C6H4Me2-Isoxazolin-3-yl0
12644-Cl—C6H4Me2-Isoxazolin-3-yl0
12653-Me—C6H4Me2-Isoxazolin-3-yl0
12664-Me—C6H4Me2-Isoxazolin-3-yl0
12674-Et—C6H4Me2-Isoxazolin-3-yl0
12684-NO2p13 C6H4Me2-Isoxazolin-3-yl0
12693,4-Cl2—C6H3Me2-Isoxazolin-3-yl0
12703,5-Cl2—C6H3Me2-Isoxazolln-3-yl0
12713,4-Me2—C6H3Me2-Isoxazolin-3-yl0
12723,5-Me2p13 C6H3Me2-Isoxazolin-3-yl0
12733-PhO—C6H4Me2-Isoxazolin-3-yl0
12744-Cl-3-Et—C6H3Me2-Isoxazolin-3-yl0
12753-EtO—C6H4Me2-Isoxazolin-3-yl0
12763-CF3—C6H4Me2-Isoxazolin-3-yl0
12774-CF3—C6H4Me2-Isoxazolin-3-yl0
12783-i-PrO—C6H4Me2-Isoxazolin-3-yl0
12793-i-Pr—C6H4Me2-Isoxazolin-3-yl0
12804-Cl-3-Me—C6H3Me2-Isoxazolin-3-yl0
1281Pyridin-2-ylMe2-Isoxazolin-3-yl1
1282Pyridin-3-ylMe2-Isoxazolin-3-yl1
12835-Cl-Me2-Isoxazolin-3-yl1
pyridin-2-yl
12843-Cl-Me2-Isoxazolin-3-yl1
pyridin-2-yl
12856-Cl-Me2-Isoxazolin-3-yl1
pyridin-2-yl
12862-Cl-Me2-Isoxazolin-3-yl1
pyridin-3-yl
12875-CF3-Me2-Isoxazolin-3-yl1
pyridin-2-yl
12883-CF3-Me2-Isoxazolin-3-yl1
pyridin-2-yl
12896-CF3-3-Cl-Me2-Isoxazolin-3-yl1
pyridin-2-yl
12905-CF3-3-Cl-Me2-Isoxazolin-3-yl1
pyridin-2-yl
1291Benzothiazol-Me2-Isoxazolin-3-yl1
2-yl
1292Benzoxazol-Me2-Isoxazolin-3-yl1
2-yl
1293Quinolin-2-ylMe2-Isoxazolin-3-yl1
12945-CF3-1,3,4-Me2-Isoxazolin-3-yl1
thiadiazol-2-yl
1295Pyrimidin-2-ylMe2-Isoxazolin-3-yl1
12965-Cl-6-Me-Me2-Isoxazolin-3-yl1
pyrimidin-4-yl
12975-Et-6-Me-Me2-Isoxazolin-3-yl1
pyrimidin-4-yl
12986-Cl-Me2-Isoxazolin-3-yl1
pyrazin-2-yl
12993,6-Me2-Me2-Isoxazolin-3-yl
pyrazin-2-yl
13005-Me-Me2-Isoxazolin-3-yl1
isoxazol-3-yl
1301C6H5Me2-Oxazolin-2-yl1mp 69-70° C.
13022-F—C6H4Me2-Oxazolin-2-yl1
13033-F—C6H4Me2-Oxazolin-2-yl1
13044-F—C6H4Me2-Oxazolin-2-yl1
13052-Cl—C6H4Me2-Oxazolin-2-yl1mp 89-90° C.
13063-Cl—C6H4Me2-Oxazolin-2-yl1mp 82-83° C.
13074-Cl‘C6H4Me2-Oxazolin-2-yl1mp 76-80° C.
13083-Br—C6H4Me2-Oxazolin-2-yl1
13094-Br—C6H4Me2-Oxazolin-2-yl1
13102-Me—C6H4Me2-Oxazolin-2-yl11H-NMR(CDCl3) δ ppm:
2.30(3H, s), 4.02(2H, t, J=9.8),
4.05(3H, s), 4.32(2H, t, J=9.8),
5.25(2H, s), 6.82(1H, d,
J=8.3), 6.86(1 H, t, J=7.6),
7.10-7.16(2H, m), 7.35(1H, t,
J=7.6), 7.41-7.48(2H, m),
7.68(1H, d, J=7.6)
13113-Me—C6H4Me2-Oxazolin-2-yl11H-NMR(CDC3) δ ppm:
2.31(3H, s), 4.00(2H, t, J=9.8),
4.03(3H, s), 4.32(2H, t, J=9.8),
5.21(2H, s), 6.72-6.78(3H, m),
7.14(1H, t, J=7.6), 7.31-
7.48(3H, m), 7.62(1H, d,
J=7.6)
13124-Me—C6H4Me2-Oxazolin-2-yl11H-NMR(CDCl3) δ ppm:
2.27(3H, s), 4.00(2H, t, J=9.6).
4.03(3H, s), 4.31(2H, t, J=9.6),
5.20(2H, s), 6.84(2H, d,
J=8.6), 7.06(21-i, d, J=8.6),
7.31-7.47(3H, m), 7.62(1 H, d,
J=7.6)
13133-Et—C6H4Me2-Oxazolin-2-yl1
13142-MeO—C6H4Me2-Oxazolin-2-yl1
13153-MeO—C6H4Me2-Oxazolin-2-yl1
13164-MeO—C6H4Me2-Oxazolin-2-yl1
13174-Et—C6H4Me2-Oxazolin-2-yl1
13183-CF3—C6H4Me2-Oxazolin-2-yl1
13194-CF3—C6H4Me2-Oxazolin-2-yl1
13203,5-F2—C6H3Me2-Oxazolin-2-yl1
13212,3-Cl2—C6H3Me2-Oxazolin-2-yl1
13222,4-Cl2—C6H3Me2-Oxazolin-2-yl1
13232,5-Cl2—C6H3Me2-Oxazolin-2-yl1
13243,4-Cl2—C6H3Me2-Oxazolin-2-yl1
13253,5-Cl2—C6H3Me2-Oxazolin-2-yl1
13262,3-Me2—C5H3Me2-Oxazolin-2-yl1
13272,4-Me2—C6H3Me2-Oxazolin-2-yl1
13282,5-Me2—C6H3Me2-Oxazolin-2-yl1mp 81-85° C.
13293,4-Me2—C6H3Me2-Oxazolin-2-yl1
13302-Cl-4-Me—C6H3Me2-Oxazolin-2-yl1
13312-Cl-5-Me—C6H3Me2-Oxazolin-2-yl1
13324-Cl-3-Me—C6H3Me2-Oxazolin-2-yl1
13333-Ph—C6H4Me2-Oxazolin-2-yl1
13343-i-PrO—C6H4Me2-Oxazolin-2-yl1
13353-PhO—C6H4Me2-Oxazolin-2-yl1
13364-Cl-2-Me—C6H3Me2-Oxazolin-2-yl1
13374-Cl-3-Et—C6H3Me2-Oxazolin-2-yl1
13383-EtO—C6H4Me2-Oxazolin-2-yl1
13392-Cl-4-Me—C6H3Me2-Oxazolin-2-yl1
13402,4,5-Cl3—C6H2Me2-Oxazolin-2-yl1
1341C6H5Me2-Oxazolin-2-yl0Isomer A: 1H-NMR(CDCl3) δ
ppm: 3.63(2H, t, J=9.8),
4.08(308(2H, t, J=9.8), 6.94-
7.40(8H, m), 7.69(1 H, dd,
J=7.9, 1.9)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 3.91 (2H, t, J=9.8),
3.96(3H, s), 4.37(2H, t, J=9.8),
6.91-7.37(9H, m)
13424-F—C6H4Me2-Oxazolin-2-yl0
13433-Cl—C6H4Me2-Oxazolin-2-yl0
13444-Cl—C6H4Me2-Oxazolin-2-yl0
13454-Me—C6H4Me2-Oxazolin-2-yl0
13463,5-Cl2—C6H3Me2-Oxazolin-2-yl0
13473,4-Me2—C6H3Me2-Oxazolin-2-yl0
13182-Cl-Me2-Oxazolin-2-yl1
pyridin-3-yl
13495-CF3-Me2-Oxazolin-2-yl1
pyridin-2-yl
13505-Cl-Me2-Oxazolin-2-yl1
pyridin-2-yl
1351C6H5Me5-Me-2-isoxazolin-1
3-yl
13522-F—C6H4Me5-Me-2-isoxazolin-1
3-yl
13533-F—C6H4Me5-Me-2-isoxazolin-1
3-yl
13544-F—C6H4Me5-Me-2-isoxazolin-1
3-yl
13552-Cl—C6H4Me5-Me-2-isoxazolin-1
3-yl
13563-Cl—C6H4Me5-Me-2-isoxazolin-1
3-yl
13574-Cl—C6H4Me5-Me-2-isoxazolin-1
3-yl
13583-Br—C6H4Me5-Me-2-isoxazolin-1
3-yl
13594-Br—C6H4Me5-Me-2-isoxazolin-1
3-yl
13602-Me—C6H4Me5-Me-2-isoxazolin-1
3-yl
13613-Me—C6H4Me5-Me-2-isoxazolin-1
3-yl
13624-Me—C6H4Me5-Me-2-isoxazolin-1
3-yl
13633-Et—C6H4Me5-Me-2-isoxazolin-1
3-yl
13642-MeO—C6H4Me5-Me-2-isoxazolin-1
3-yl
13653-MeO—C6H4Me5-Me-2-isoxazolin-1
3-yl
13664-MeO—C6H4Me5-Me-2-isoxazolin-1
3-yl
13674-Et—C6H4Me5-Me-2-isoxazolin-1
3-yl
13683-CF3—C6H4Me5-Me-2-isoxazolin-1
3-yl
13694-CF3—C6H4Me5-Me-2-isoxazolin-1
3-yl
13703,5-F2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13712,3-Cl2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13722,4-Cl2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13732,5-Cl2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13743,4-Cl2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13753,5-Cl2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13762,3-Me2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13772,4-Me2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13782,5-Me2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13793,4-Me2—C6H3Me5-Me-2-isoxazolin-1
3-yl
13802-C1-4-Me—C6H3Me5-Me-2-isoxazolin-1
3-yl
13812-Cl-5-Me—C6H3Me5-Me-2-isoxazolin-1
3-yl
13824-Cl-3-Me—C6H3Me5-Me-2-isoxazolin-1
3-yl
13833-Ph—C6H4Me5-Me-2-isoxazolin-1
3-yl
13843-i-PrO—C6H4Me5-Me-2-isoxazolin-1
3-yl
13853-PhO—C6H4Me5-Me-2-isoxazolin-1
3-yl
13864-Cl-2-Me—C6H3Me5-Me-2-isoxazolin-1
3-yl
13874-Cl-3-Et—C6H3Me5-Me-2-isoxazolin-1
3-yl
13883-EtO—C6H4Me5-Me-2-isoxazolin-1
3-yl
13892-Cl-4-Me—C6H3Me5-Me-2-isoxazolin-1
3-yl
13902,4,5-Cl3—C6H2Me5-Me-2-isoxazolin-1
3-yl
1391C6H5Me5-Me-2-isoxazolin-0
3-yl
13924-F—C6H4Me5-Me-2-isoxazolin-0
3-yl
13933-Cl—C6H4Me5-Me-2-isoxazolin-0
3-yl
13944-Cl—C6H4Me5-Me-2-isoxazolin-0
3-yl
13954-Me—C6H4Me5-Me-2-isoxazolin-0
3-yl
13963,5-Cl2—C6H3Me5-Me-2-isoxazolin-0
3-yl
13973,4-Me2—C6H3Me5-Me-2-isoxazolin-0
3-yl
13982-Cl-Me5-Me-2-isoxazolin-1
pyridin-3-yl3-yl
13995-CF3-Me5-Me-2-isoxazolin-1
pyridin-2-yl3-yl
14005-Cl-Me5-Me-2-isoxazolin-1
pyridin-2-yl3-yl
1401C6H5Meimidazol-2-yl1
14022-F—C6H4MeImidazol-2-yl1
14033-F—C6H4MeImidazol-2-yl1
14044-F—C6H4MeImidazol-2-yl1
14052-Cl—C6H4MeImidazol-2-yl1
14063-Cl—C6H4MeImidazol-2-yl 1
14074-Cl—C6H4MeImidazol-2-yl1
14083-Br—C6H4MeImidazol-2-yl1
14094-Br—C6H4MeImidazol-2-yl1
14102-Me—C6H4MeImidazol-2-yl1
14113-Me—C6H4MeImidazol-2-yl1
14124-Me—C6H4MeImidazol-2-yl1
14133-Et—C6H4MeImidazol-2-yl1
14142-MeO—C6H4MeImidazol-2-yl1
14153-MeO—C6H4MeImidazol-2-yl1
14164-MeO—C6H4MeImidazol-2-yl1
14174-Et—C6H4MeImidazol-2-yl1
14183-CF3—C6H4MeImidazol-2-yl1
14194-CF3—C6H4MeImidazol-2-yl1
14203,5-F2—C6H3MeImidazol-2-yl1
14212,3-Cl2—C6H3MeImidazol-2-yl1
14222,4-Cl2—C6H3MeImidazol-2-yl1
14232,5-Cl2—C6H3MeImidazol-2-yl1
14243,4-Cl2—C6H3MeImidazol-2-yl1
14253,5-Cl2—C6H3MeImidazol-2-yl1
14262,3-Me2—C6H3MeImidazol-2-yl1
14272,4-Me2—C6H3MeImidazol-2-yl1
14282,5-Me2—C6H3MeImidazol-2-yl1mp 153-154° C.
14293,4-Me2—C6H3MeImidazol-2-yl1
14302-Cl-4-Me—C6H3MeImidazol-2-yl1
14312-Cl-5-Me—C6H3MeImidazol-2-yl1
14324-Cl-3-Me—C6H3MeImidazol-2-yl1
14333-Ph—C6H4MeImidazol-2-yl1
14343-i-PrO—C6H4MeImidazol-2-yl1
14353-PhO—C6H4MeImidazol-2-yl1
14364-Cl-2-Me—C6H3MeImidazol-2-yl1
14374-Cl-3-Et—C6H3MeImidazol-2-yl1
14383-EtO—C6H4MeImidazol-2-yl1
14392-Cl-4-Me—C6H3MeImidazol-2-yl1
14402,4,5-Cl3—C6H2MeImidazol-2-yl1
1441C6H5MeImidazol-2-yl0
14424-F—C6H4MeImidazol-2-yl0
14433-Cl—C6H4MeImidazol-2-yl0
14444-Cl—C6H4MeImidazol-2-yl0
14454-Me—C6H4MeImidazol-2-yl0
14463,5-Cl2—C6H3MeImidazol-2-yl0
14473,4-Me2—C6H3MeImidazol-2-yl0
14482-Cl-MeImidazol-2-yl1
pyridin-3-yl
14495-CF3-MeImidazol-2-yl1
pyridin-2-yl
14505-Cl-MeImidazol-2-yl1
pyridin-2-yl
1451C6H5Me2-Imidazolin-2-yl1mp 91-92° C.
14522-F—C6H4Me2-Imidazolin-2-yl1
14533-F—C6H4Me2-Imidazolin-2-yl1
14544-F—C6H4Me2-Imidazolin-2-yl1
14552-Cl—C6H4Me2-Imidazolin-2-yl1mp 121-123° C.
14563-Cl—C6H4Me2-Imidazolin-2-yl11H-NMR(CDCl3) δ ppm:
3.67(4H, brs), 3.95(4.02)(3H,
s), 4.97(5.11)(2H, s), 6.78-
6.81(1H, m), 6.90-6.95(2H, m),
7.13-7.23(2H, m), 7.35-
7.41(2H, m), 7.49-7.51(1H, m)
14574-Cl—C6H4Me2-Imidazolin-2-yl1mp 113-114° C.
14583-Br—C6H4Me2-Imidazolin-2-yl1
14594-Br—C6H4Me2-Imidazolin-2-yl1
14602-Me—C6H4Me2-Imidazolin-2-yl1mp 96-100° C.
14613-Me—C6H4Me2-Imidazolin-2-yl11H-NMR(CDCl3) δ ppm:
2.31(2.27)(3H, s), 3.66(4H,
brs), 4.02(3.94)(3H, s),
5.11(4.95)(2H, s), 6.54-
6.76(3H, m), 7.04-7.15(1H, m),
7.21-7.41(3H, m), 7.50-
7.53(1H, m)
14624-Me—C6H4Me2-Imidazolin-2-yl1mp 89-90° C.
14633-Et—C6H4Me2-Imidazolin-2-yl1
14642-MeO—C6H4Me2-Imidazolin-2-yl1
14653-MeO—C6H4Me2-Imidazolin-2-yl1
14664-MeO—C6H4Me2-Imidazolin-2-yl1
14674-Et—C6H4Me2-Imidazolin-2-yl1
14683-CF3—C6H4Me2-Imidazolin-2-yl1
14694-CF3—C6H4Me2-Imidazolin-2-yl1
14703,5-F2—C6H3Me2-Imidazolin-2-yl1
14712,3-Cl2—C6H3Me2-Imidazolin-2-yl1
14722,4-Cl2—C6H3Me2-Imidazolin-2-yl1
14732,5-Cl2—C6H3Me2-Imidazolin-2-yl1
14743,4-Cl2—C6H3Me2-Imidazolin-2-yl1
14753,5-Cl2—C6H3Me2-Imidazolin-2-yl1
14762,3-Me2—C6H3Me2-Imidazolin-2-yl1
14772,4-Me2—C6H3Me2-Imidazolin-2-yl1
14782,5-Me2—C6H3Me2-Imidazolin-2-yl1mp 97-101° C.
14793,4-Me2—C6H3Me2-Imidazolin-2-yl1
14802-Cl-4-Me—C6H3Me2-Imidazolin-2-yl1
14812-Cl-5-Me—C6H3Me2-Imidazolin-2-yl1
14824-Cl-3-Me—C6H3Me2-Imidazolin-2-yl1
14833-Ph—C6H4Me2-Imidazolin-2-yl1
14843-i-PrO—C6H4Me2-Imidazolin-2-yl1
14853-PhO—C6H4Me2-Imidazolin-2-yl1
14864-Cl-2-Me—C6H3Me2-Imidazolin-2-yl1
14874-Cl-3-Et—C6H3Me2-Imidazolin-2-yl1
14883-EtO—C6H4Me2-Imidazolin-2-yl1
14892-Cl-4-Me—C6H3Me2-Imidazolin-2-yl1
14902,4,5-Cl3—C6H2Me2-Imidazolin-2-yl 1
1491C6H5Me2-Imidazolin-2-yl0mp 95-99° C.
14924-F—C6H4Me2-Imidazolin-2-yl0
14933-Cl—C6H4Me2-Imidazolin-2-yl0
14944-Cl—C6H4Me2-Imidazolin-2-yl0
14954-Me—C6H4Me2-Imidazolin-2-yl0
14963,5-Cl2—C6H3Me2-Imidazolin-2-yl0
14973,4-Me2—C6H3Me2-Imidazolin2-yl0
14982-Cl-Me2-Imidazolin-2-yl1
pyridin-3-yl
14995-CF3-Me2-Imidazolin-2-yl1
pyridin-2-yl
15005-Cl-Me2-Imidazolin-2-yl1
pyridin-2-yl
1501C6H5Me2-Thiazolin-2-yl1
15022-Cl—C6H4Me2-Thiazolin-2-yl1
15033-Cl—C6H4Me2-Thiazolin-2-yl1
15044-Cl—C6H4Me2-Thiazolin-2-yl1
15052-Me—C6H4Me2-Thiazolin-2-yl1
15063-Me—C6H4Me2-Thiazolin-2-yl1
15074-Me—C6H4Me2-Thiazolin-2-yl1
15082-MeO—C6H4Me2-Thiazolin-2-yl1
15094-Br—C6H4Me2-Thiazolin-2-yl1
15103-CF3—C6H4Me2-Thiazolin-2-yl1
15112,4-Cl2—C6H3Me2-Thiazolin-2-yl1
15122,5-Cl2—C6H3Me2-Thiazolin-2-yl1
15132,4-Me2—C6H3Me2-Thiazolin-2-yl1
15142,5-Me2—C6H3Me2-Thiazolin-2-yl1mp 79-82° C.
1515C6H5Me2-Thiazolin-2-yl01H-NMR(CDCl3) δ ppm:
2.88(3.22)(2H, t, J=8.0),
3.90(4.29)(2H, t, J=8.0),
4.06(3.95)(3H, s), 6.91-
7.58(9H, m)
15164-Cl—C6H4Me2-Thiazolin-2-yl0
15174-Me—C6H4Me2-Thiazolin-2-yl0
15182-Cl-Me2-Thiazolin-2-yl1
pyridin-3-yl
15195-CF3-Me2-Thiazolin-2-yl1
pyridin-2-yl
15205-Cl-Me2-Thiazolin-2-yl1
pyridin-2-yl
1521C6H5MeThiazol-2-yl1
15222-Cl—C6H4MeThiazol-2-yl1
15233-Cl—C6H4MeThiazol-2-yl1
15244-Cl—C6H4MeThiazol-2-yl1
15252-Me—C6H4MeThiazol-2-yl1
15263-Me—C6H4MeThiazol-2-yl1
15274-Me—C6H4MeThiazol-2-yl1
15282-MeO—C6H4MeThiazol-2-yl1
15294-Br—C6H4MeThiazol-2-yl1
15303-CF3—C6H4MeThiazol-2-yl1
15322,5-Cl2—C6H3MeThiazol-2-yl1
15332,4-Me2—C6H3MeThiazol-2-yl1
15342,5-Me2—C6H3MeThiazol-2-yl1mp 112-113.5° C.
1535C6H5MeThiazol-2-yl0
15364-Cl—C6H4MeThiazol-2-yl0
15374-Me—C6H4MeThiazol-2-yl0
15382-Cl-MeThiazol-2-yl1
pyridin-3-yl
15395-CF3-MeThiazol-2-yl 1
pyridin-2-yl
15405-Cl-MeThiazol-2-yl1
pyridin-2-yl
1541C6H5Me1-Me-pyrazol-5-yl1
15422-Cl—C6H4Me1-Me-pyrazol-5-yl1
15433-Cl—C6H4Me1-Me-pyrazol-5-yl1
15444-Cl—C6H4Me1-Me-pyrazol-5-yl1
15452-Me—C6H4Me1-Me-pyrazol-5-yl1
15463-Me—C6H4Me1-Me-pyrazol-5-yl1
15474-Me—C6H4Me1-Me-pyrazol-5-yl1
15482-MeO—C6H4Me1-Me-pyrazol-5-yl1
15494-Br—C6H4Me1-Me-pyrazol-5-yl1
15502,5-Me2—C6H3Et1-Me-pyrazol-5-yl1Isomer A: mp 74-76° C.
Isomer B: mp 84-86° C.
15512,4-Cl2—C6H3Me1-Me-pyrazol-5-yl1
15522,5-Cl2—C6H3Me1-Me-pyrazol-5-yl1
15532,4-Me2—C6H3Me1-Me-pyrazol-5-yl1
15542,5-Me2—C6H3Me1-Me-pyrazol-5-yl1Isomer A: 1H-NMR(CDCl3) δ
ppm: 2.12(3H, s), 2.24(3H, s),
3.98(3H, s), 4.12(3H, s),
4.93(2H, s), 5.92(1H, d,
J=1.8), 6.52(1H, s), 6.64-
7.64(7H, m)
Isomer B: mp 108-110° C.
1555C6H5Me1-Me-pyrazol-5-yl0
15564-Cl—C6H4Me1-Me-pyrazol-5-yl0
15574-Me—C6H4Me1-Me-pyrazol-5-yl0
15582-Cl-Me1-Me-pyrazol-5-yl1
pyridin-3-yl
15595-CF3-Me1-Me-pyrazol-6-yl1
pyridin-2-yl
15605-Cl-Me1-Me-pyrazol-5-yl1
pyridin-2-yl
1561C6H5Me1-Me-1,2,4-triazol-11H-NMR(CDCl3) δ ppm:
5-yl4.00(3H, s), 4.03(3H, s),
4.92(2H, s), 6.74-6.94(3H, m),
7.18-7.57(5H, m), 7.83(1H, s)
15622-Cl—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15633-Cl—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15644-Cl—C6H4Me1-Me-1,2,4-triazol-1mp 113-114°]C.
5-yl
15652-Me—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15663-Me—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15674-Me—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15682-MeO—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15694-Br—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15703-CF3—C6H4Me1-Me-1,2,4-triazol-1
5-yl
15712,4-Cl2—C6H3Me1-Me-1,2,4-triazol-1
5-yl
15722,5-Cl2—C6H3Me1-Me-1,2,4-triazol-1
5yl
15732,4-Me2—C6H3Me1-Me-1,2,4-triazol-1
5-yl
15742,5-Me2—C6H3Me1-Me-1,2,4-triazol-1mp 101-102° C.
5-yl
1575C6H5Me1-Me-1,2,4-triazol-13.98(6H, s), 6.85-7.48(9H, m),
5-yl7.80(1H, s)
15764-Cl—C6H4Me1-Me-1,2,4-triazol-0
5-yl
15774-Me—C6H4Me1-Me-1,2,4-triazol-0
5-yl
15782-Cl-Me1-Me-1,2,4-triazol-1mp 99-100° C.
pyridin-3-yl5-yl
15795-CF3-Me1-Me-1,2,4-triazol-1
pyridin-2-yl5-yl
15805-Cl-Me1-Me-1,2,4-triazol-1
pyridin-2-yl5-yl
1581C6H5Me1,2,4-Oxadiazol-5-yl1mp 109.0-110.0° C.
15822-Cl—C6H4Me1,2,4-Oxadiazol-5-yl1
15833-Cl—C6H4Me1,2,4-Oxadiazol-5-yl1
15844-Cl—C6H4Me1,2,4-Oxadiazol-5-yl1mp 96-97.5° C.
15852-Me—C6H4Me1,2,4-Oxadiazol-5-yl1
15863-Me—C6H4Me1,2,4-Oxadiazol-5-yl1
15874-Me—C6H4Me1,2,4-Oxadiazol-5-yl1
15882-MeO—C6H4Me1,2,4-Oxadiazol-5-yl1
15894-Br—C6H4Me1,2,4-Oxadiazol-5-yl1
15902,5-Me2—C6H3Me3-Et-1,2,4-1mp 111.5-112.5° C.
oxadiazol-5-yl
15912,4-Cl2—C6H3Me1,2,4-Oxadiazol-5-yl1
15922,5-Cl2—C6H3Me1,2,4-Oxadiazol-5-yl1
15932,4-Me2—C6H3Me1,2,4-Oxadiazol-5-yl1
15942,5-Me2—C6H3Me1,2,4-Oxadiazol-5-yl1mp 75-76° C.
1595C6H5Me1,2,4-Oxadiazol-5-yl0mp 115.5-116.5° C.
15964-Cl—C6H4Me1,2,4-Oxadiazol-5-yl0
15974-Me—C6H4Me1,2,4-Oxadiazol-5-yl0
15982-Cl-Me1,2,4-Oxadiazol-5-yl1
pyridin-3-yl
15995-CF3-Me1,2,4-Oxadiazol-5-yl1
pyridin-2-yl
16005-Cl-Me1,2,4-Oxadiazol-5-yl1
pyridin-2-yl
1601C6H5Me2-Thienyl1
16022-Cl-C6H4Me2-Thienyl1
16033-Cl—C6H4Me2-Thienyl1
16044-Cl—C6H4Me2-Thienyl1
16052-Me—C6H4Me2-Thienyl1
16063-Me—C6H4Me2-Thienyl1
16074-Me—C6H4Me2-Thienyl1
16082-MeO—C6H4Me2-Thienyl1
16094-Br—C6H4Me2-Thienyl1
16103-CF3—C6H4Me2-Thienyl1
16112,4-Cl2—C6H3Me2-Thienyl1
16122,5-Cl2—C6H3Me2-Thienyl1
16132,4-Me2—C6H3Me2-Thienyl1
16142,5-Me2—C6H3Me2-Thienyl1Isomer A: mp 81-84° C.
Isomer B: mp 106-107° C.
1615C6H5Me2-Thienyl0
16164-Cl—C6H4Me2-Thienyl0
16174-Me—C6H4Me2-Thienyl0
16182-Cl-Me2-Thienyl1
pyridin-3-yl
16195-CF3-Me2-Thienyl1
pyridin-2-yl
16205-Cl-Me2-Thienyl1
pyridin-2-yl
1621C6H5Me2-Furyl1
16222-Cl—C6H4Me2-Furyl1
16233-Cl—C6H4Me2-Furyl1
16244-Cl—C6H4Me2-Furyl1
16252-Me—C6H4Me2-Furyl1
16263-Me—C6H4Me2-Furyl1
16274-Me—C6H4Me2-Furyl1
16282-MeO—C6H4Me2-Furyl1
16294-Br—C6H4Me2-Furyl1
16303-CF3—C6H4Me2-Furyl1
16312,4-Cl2—C6H3Me2-Furyl1
16322,5-Cl2—C6H3Me2-Furyl1
16332,4-Me2—C6H3Me2-Furyl1
16342,5-Me2—C6H3Me2-Furyl1Isomer A: mp 81-82° C.
Isomer B: mp 110-112° C.
1635C6H5Me2-Furyl0
16364-Cl—C6H4Me2-Furyl0
16374-Me—C6H4Me2-Furyl0
16382-Cl-Me2-Furyl0
pyridin-3-yl
16395-CF3-Me2-Furyl1
pyridin-2-yl
16405-Cl-Me2-Furyl1
pyridin-2-yl
1641C6H5Me3-Me-isothiazol-5-yl1
16422-Cl—C6H4MeIsothiazol-5-yl1
16433-Cl—C6H4MeIsothiazol-5-yl1
16444-Cl—C6H4Me3-Me-isothiazol-5-1
16452-Me—C6H4Me3-Me-isothiazol-5-yl1
16463-Me—C6H4MeIsothiazol-5-yl1
16474-Me—C6H4MeIsothiazol-5-yl1
16482-MeO—C6H4MeIsothiazol-5-yl1
16494-Br—C6H4MeIsothiazol-5-yl1
16503-CF3—C6H4MeIsothiazol-5-yl1
16512,4-Cl2—C6H3MeIsothiazol-5-yl1
16522,5-Cl2—C6H3MeIsothiazol-5-yl1
16532,4-Me2—C6H3MeIsothiazol-5-yl1
16542,5-Me2—C6H3Me3-Me-isothiazol-5-yl11H-NMR(CDCl3) δ ppm:
2.06(3H, s), 2.23(3H, s),
2.40(3H, s), 4.21 (3H, s),
5.01(2H, s), 6.51(1H, s), 6.60-
6.65(1H, m), 6.71(1H, s),
6.96(1H, d, J=7.9), 7.37-
7.71(4H, m)
1655C6H5MeIsothiazol-5-yl0
16564-Cl—C6H4MeIsothiazol-5-yl0
16574-Me—C6H4MeIsothiazol-5-yl0
16582-Cl-MeIsothiazol-5-yl1
pyridin-3-yl
16595-CF3-MeIsothiazol-5-yl1
pyridin-2-yl
16605-Cl-MeIsothiazol-5-yl1
pyridin-2-yl
1661C6H5EtIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
1.35(1.28)(3H, t, J=7.3),
4.31(4.26)(2H, q, J=7.3),
5.06(4.98)(2H, s), 6.81-
7.60(10H, m), 8.46(8.38)(1H,
d, J=1.8)
16622-Cl—C6H4EtIsoxazol-3-yl1
16633-Cl—C6H4EtIsoxazol-3-yl1
16644-Cl—C6H4EtIsoxazol-3-yl1
16652-Me—C6H4EtIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
1.36(1.28)(3H, t, J=7.3),
2.20(2.18)(3H, s), 4.23-
4.37(2H, m), 5.04(4.98)(2, s),
6.68-7.63(9H, m),
8.44(8.38)(1H, d, J=1.8)
16663-Me—C6H4EtIsoxazol-3-yl1
16672-Me—C6H4AllylIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
2.20(2.17)(3H, s), 4.69-
4.78(2H, m), 5.05(4.98)(2H, s),
5.18-5.38(2H, m), 5.92-
6.08(1H, m), 6.69-7.63(9H, m),
8.45(8.38)(1H, d, J=1.8)
16882-MeO—C6H4EtIsoxazol-3-yl1
16694-Br—C6H4EtIsoxazol-3-yl1
16703-CF3—C6H4EtIsoxazol-3-yl1
16712,4-Cl2—C6H3EtIsoxazol-3-yl1
16722,5-Cl2—C6H3EtIsoxazol-3-yl1
16732,4-Me2—C6H3EtIsoxazol-3-yl1
16742,5-Me2—C6H3EtIsoxazol-3-yl11H-NMR(CDCl3) δ ppm:
1.37(1.29)(3H, t, J=7.3),
2.16(2.13)(3H, s),
2.25(2.22)(3H, s), 4.23-
4.38(2H, m), 5.03(4.96)(2H, s),
6.53-7.64(8H, m),
8.45(8.39)(1H, d, J=1.8)
1675C6H5EtIsoxazol-3-yl0
16764-Cl—C6H4EtIsoxazol-3-yl0
16774-Me—C6H4EtIsoxazol-3-yl0
16782-Cl-EtIsoxazol-3-yl1
pyridin-3-yl
16795-CF3-EtIsoxazol-3-yl1
pyridin-2-yl
16805-Cl-EtIsoxazol-3-yl1
pyridin-2-yl
1681C6H5Me1,3,4-Thiadiazol-2-yl1
16822-Cl—C6H4Me1,3,4-Thiadiazol-2-yl1
16833-Cl—C6H4Me1,3,4-Thiadiazol-2-yl1
16844-Cl—C6H4Me1,3,4-Thiadiazol-2-yl1
16852-Me—C6H4Me1,3,4-Thiadiazol-2-yl1
16863-Me—C6H4Me1,3,4-Thiadiazol-2-yl1
16874-Me—C6H4Me1,3,4-Thiadiazol-2-yl1
16882-MeO—C6H4Me1,3,4-Thiadiazol-2-yl1
16894-Br—C6H4Me1,3,4-Thiadiazol-2-yl1
16903-CF3—C6H4Me1,3,4-Thiadiazol-2-yl1
16912,4-Cl2—C6H3Me1,3,4-Thiadiazol-2-yl1
16922,5-Cl2—C6H3Me1,3,4-Thiadiazol-2-yl1
16932,4-Me2—C6H3Me1,3,4-Thiadiazol-2-yl1
16942,5-Me2—C6H3Me1,3,4-Thiadiazol-2-yl1
1695C6H5Me1,3,4-Thiadiazol-2-yl0
16964-Cl—C6H4Me1,3,4-Thiadiazol-2-yl0
16974-Me—C6H4Me1,3,4-Thiadiazol-2-yl0
16982-Cl-Me1,3,4-Thiadiazol-2-yl1
pyridin-3-yl
16995-CF3-Me1,3,4-Thiadiazol-2-yl1
pyridin-2-yl
17005-Cl-Me1,3,4-Thiadiazol-2-yl1
pyridin-2-yl
1701C6H5MeOxazol-2-yl1
17022-Cl—C6H4MeOxazol-2-yl1
17033-Cl—C6H4MeOxazol-2-yl1
17044-Cl—C6H4MeOxazol-2-yl1
17052-Me—C6H4MeOxazol-2-yl1
17063-Me—C6H4MeOxazol-2-yl1
17074-Me—C6H4MeOxazol-2-yl1
17082-MeO—C6H4MeOxazol-2-yl1
17094-Br—C6H4MeOxazol-2-yl1
17103-CF3—C6H4MeOxazol-2-yl1
17112,4-Cl2—C6H3MeOxazol-2-yl1
17122,5-Cl2—C6H3MeOxazol-2-yl1
17132,4-Me2—C6H3MeOxazol-2-yl1
17142,5-Me2—C6H3MeOxazol-2-yl1
1715C6H5MeOxazol-2-yl0
17164-Cl—C6H4MeOxazol-2-yl0
17174-Me—C6H4MeOxazol-2-yl0
17182-Cl-MeOxazol-2-yl1
pyridin-3-yl
17195-CF3-MeOxazol-2-yl1
pyridin-2-yl
17205-Cl-MeOxazol-2-yl1
pyridin-2-yl
1721C6H5MeOxazol-5-yl11H-NMR(CDCl3) δ ppm:
4.00(385),(3H, s),
4.98(4.97)(2H, s), 6.78-
7.66(10H, m), 7.92(1H, s)
17222-Cl—C6H4MeOxazol-5-yl1
17233-Cl—C6H4MeOxazol-5-yl1
17244-Cl—C6H4MeOxazol-5-yl1mp 71-73° C.
17252-Me—C6H4MeOxazol-5-yl1
17263-Me—C6H4MeOxazol-5-yl1
17274-Me—C6H4MeOxazol-5-yl1
17282-MeO—C6H4MeOxazol-5-yl1
17294-Br—C6H4MeOxazol-5-yl1
17303-CF3—C6H4MeOxazol-5-yl13.99(3H, s), 5.01(2H, s),
6.88(1H, s),
6.94-7.62(8H, m), 7.93(1H, s)
17312,4-Cl2—C6H3MeOxazol-5-yl1
17322,5-Cl2—C6H3MeOxazol-5-yl1
17332,4-Me2—C6H3MeOxazol-5-yl1
17342,5-Me2—C6H3MeOxazol-5-yl1mp 90-91° C.
1735C6H5MeOxazol-5-yl0mp 76.5-77.5° C.
17364-Cl—C6H4MeOxazol-5-yl0
17374-Me—C6H4MeOxazol-5-yl0
17382-Cl-MeOxazol-5-yl1
pyridin-3-yl
17395-CF3-MeOxazol-5-yl1
pyridin-2-yl
17405-Cl-MeOxazol-5-yl1
pyridin-2-yl
1741C6H5Me5,5-Me2-2-1
isoxazolin-3-yl
17422-Cl—C6H4Me5,5-Me2-2-1
isoxazolin-3-yl
17433-Cl—C6H4Me5,5-Me2-2-1
isoxazolin-3-yl
17444-Cl—C6Hhd 4Me5,5-Me2-2-1
isoxazolin-3-yt
17452-Me—C6H4Me5,5-Me2-2-1
isoxazolin-3-yl
17463-Me—C6H4Me5,5-Me2-2-1
isoxazolin-3-yl
17474-Me—C6H4Me5,5-Me2-2-1
isoxazolin-3-yl
17482-MeO—C6H4Me5,5-Me2-2-1
isoxazolin-3-yl
17494-Br—C6H4Me5,5-Me2-2-1
isoxazolin-3-yl
17502,5-Me2—C6H3Et5,5-Me2-2-11H-NMR(CDCl3) δ ppm:
isoxazolin-3-yl1.25(1.33)(3H, t, J=7.3),
1.36(1.55)(6H, s),
2.20(2.21(3H, s), 2.27(2.26)
(3H, s), 3.03-3.22(2H, m),
4.15-4.27(2H, m), 4.92-
5.08(2H, m), 6.57-7.53(7H, m)
17512,4-Cl2—C6H3Me5,5-Me2-2-1
isoxazolin-3-yl
17522,5-Cl2—C6H3Me5,5-Me2-2-1
isoxazolin-3-yl
17532,4-Me2—C6H3Me5,5-Me2-2-1
isoxazolin-3-yl
17542,5-Me2—C6H3Me5,5-Me2-2-1mp 86-89° C.
isoxazolin-3-yl
1755C6H5Me5,5-Me2-2-0
isoxazolin-3-yl
17564-Cl—C6H4Me5,5-Me2-2-0
isoxazolin-3-yl
17574-Me—C6H4Me5,5-Me2-2-0
isoxazolin-3-yl
17582-Cl-Me5,5-Me2-2-1
pyridin-3-ylisoxazolin-3-yl
17595-CF3-Me5,5-Me2-2-1
pyridin-2-ylisoxazolin-3-yl
17605-Cl-Me5,5-Me2-2-1
pyridin-2-ylisoxazolin-3-yl
1761C6H5Et3-Me-isoxazol-5-yl1
17622-Cl—C6H4Et3-Me-isoxazol-5-yl1
17633-Cl—C6H4Et3-Me-isoxazol-5-yl1
17644-Cl—C6H4Et3-Me-isoxazol-5-yl1Isomer A: 1H-NMR(CDCl3) δ
ppm: 1.38(3H, t, J=7.3),
2.16(3H, s), 2.34(3H, s),
4.37(2H, q, J=7.3), 5.02(2H,
s), 6.68-7.63(9H, m)
Isomer B: 1H-NMR(CDCl3) δ
ppm: 1.29(3H, t, J=7.3),
2.18(3H, s), 2.26(3H, s),
4.30(2H, q, J=7.3), 4.97(2H,
s), 5.96(1H, s), 6.70-7.67(8H, m)
17652-Me—C6H4Et3-Me-isoxazol-5-yl1
17663-Me—C6H4Et3-Me-isaxazol-5-yl1
17674-Me—C6H4Et3-Me-isoxazol-5-yl1
17682-MeO—C6H4Et3-Me-isoxazol-5-yl1
17694-Br—C6H4Et3-Me-isoxazol-5-yl1
17703-CF3—C6H4Et3-Me-isoxazol-5-yl1
17712,4-Cl2—C6H3Et3-Me-isoxazol-5-yl1
17722,5-Cl2—C6H3Et3-Me-isoxazol-5-yl1
17732,4-Me2—C6H3Et3-Me-isoxazol-5-yl1
17742,5-Me2—C6H3Et3-Me-isoxazol-5-yl1
1775C6H5Et3-Me-isoxazol-5-yl0
17764-Cl—C6H4Et3-Me-isoxazol-5-yl0
17774-Me—C6H4Et3-Me-isoxazol-5-yl0
17782-Cl-Et3-Me-isoxazol-5-yl1
pyridin-3-yl
17795-CF3-Et3-Me-isoxazol-5-yl1
pyridin-2-yl
17805-Cl-Et3-Me-isoxazol-5-yl1
pyridin-2-yl
1781C6H5Et1-Me-1
imidazol-2-yl
17822-Cl—C6H4Et1-Me-1
imidazol-2-yl
17833-Cl—C6H4Et1-Me-1
imidazol-2-yl
17844-Cl—C6H4Et1-Me-1
imidazol-2-yl
17852-Me—C6H4Et1-Me-1
imidazol-2-yl
17863-Me—C6H4Et1-Me-1
imidazol-2-yl
17874-Me—C6H4Et1-Me-1
imidazol-2-yl
17882-MeO—C6H4Et1-Me-1
imidazol-2-yl
17894-Br—C6H4Et1-Me-1
imidazol-2-yl
17903-CF3—C6H4Et1-Me-1
imidazol-2-yl
17912,4-Cl2—C6H3Et1-Me-1
imidazol-2-yl
17922,5-Cl2—C6H3Et1-Me-1
imidazol-2-yl
17932,4-Me2—C6H3Et1-Me-1
imidazol-2-yl
17942,5-Me2—C6H3Et1-Me-1
imidazol-2-yl
1795C6H5Et1-Me-0
imidazol-2-yl
17964-Cl—C6H4Et1-Me-0
imidazol-2-yl
17974-Me—C6H4Et1-Me-0
imidazol-2-yl
17982-Cl-Et1-Me-1
pyridin-3-ylimidazol-2-yl
17995-CF3-Et1-Me-1
pyridin-2-ylimidazol-2-yl
18005-Cl-Et1-Me-1
pyridin-2-ylimidazol-2-yl
1801Pyridin-2-ylMe1-Me-2-imidazolin-0
2-yl
18025-Cl-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
18033-Cl-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
18046-Cl-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
18053,5-Cl2-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
18065-CF3-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
18073-CF3-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
18086-CF3-3-Cl-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
18095-CF3-3-Cl-Me1-Me-2-imidazolin-0
pyridin-2-yl2-yl
1810Benzothiazol-Me1-Me-2-imidazolin-0
2-yl2-yl
1811Benzoxazol-Me1-Me-2-imidazolin-0
2-yl2-yl
1812Quinolin-2-ylMe1-Me-2-imidazolin-0
2-yl
18135-CF3-1,3,4-Me1-Me-2-imidazolin-0
thiadiazol-2-yl2-yl
1814Pyrimidin-2-ylMe1-Me-2-imidazolin-0
2-yl
18156-Cl-pyrimidin-4-ylMe1-Me-2-imidazolin-0
2-yl
18165-Et-6-Me-Me1-Me-2-imidazolin-0
pyrimidin-2-yl2-yl
18176-Cl-Me1-Me-2-imidazolin-0
pyrazin-2-yl2-yl
18183,6-Me2-Me1-Me-2-imidazolin-0
pyrazin-2-yl2-yl
18193-Ph-Me1-Me-2-imidazolin-0
isoxazol-5-yl2-yl
18205-Me-Me1-Me-2-tmidazolin-0
isoxazol-3-yl2-yl
1821Pyridin-2-ylMe2-Oxazolin-2-yl0
18225-Cl-Me2-Oxazolin-2-yl0
pyridin-2-yl
18233-Cl-Me2-Oxazolin-2-yl0
pyridin-2-yl
18246-Cl-Me2-Oxazolin-2-yl0
pyridin-2-yl
18253,5-Cl2-Me2-Oxazolin-2-yl01H-NMR(CDCl3) δ ppm:
pyridin-2-yl3.97(4.06)(3H, s), 3.86-
4.29(4H, m), 6.82-7.91(6H, m)
18265-CF3-Me2-Oxazolin-2-yl01H-NMR(CDCl3) δ ppm:
pyridin-2-yl3.78(2H, t, J=9.8), 3.98(3H, s),
4.16(2H, t, J=9.8), 6.94-
7.87(6H, m), 8.43(1H, brs)
18273-CF3-Me2-Oxazolin-2-yl0
pyridin-2-yl
18286-CF3-3-Cl-Me2-Oxazolin-2-yl0
pyridin-2-yl
18295-CF3-3-Cl-Me2-Oxazolin-2-yl01H-NMR(CDCl3) δ ppm:
pyridin-2-yl3.92(2H, t, J=9.8), 3.95(3H, s),
4.28(2H, t, J=9.8), 7.15-
7.95(5H, m), 8.22(1H,brs)
1830Benzothiazol-Me2-Oxazolin-2-yl01H-NMR(CDCl3) δ ppm:
2-yl
3.84(2H, t, J=9.8), 4.03(3H, s),
4.25(2H, t, J=9.8), 7.23-
7.74(8H, m)
1831Benzoxazol-Me2-Oxazolin-2-yl0mp 100-103° C.
2-yl
1832Quinolin-2-ylMe2-Oxazolin-2-yl0
18335-CF3-1,3,4-Me2-Oxazolin-2-yl0
thiadiazol-2-yl
1834Pyrimidin-2-ylMe2-Oxazolin-2-yl0
18356-Cl-pyrimidin-4-ylMe2-Oxazolin-2-yl0mp 103-105° C.
18365-Et-6-Me-Me2-Oxazolin-2-yl0
pyrimidin-2-yl
18376-Cl-Me2-Oxazolin-2-yl0
pyrazin-2-yl
18383,6-Me2-Me2-Oxazolin-2-yl0
pyrazin-2-yl
18393-Ph-Me2-Oxazolin-2-yl0
isoxazol-5-yl
18405-Me-Me2-Oxazolin-2-yl0
isoxazol-3-yl
1841Pyridin-2-ylMe2-Isoxazolin-3-yl0
18425-Cl-Me2-Isoxazolin-3-yl0
pyridin-2-yl
18433-Cl-Me2-Isoxazolin-3-yl0
pyridin-2-yl
18446-Cl-Me2-Isoxazolin-3-yl0
pyridin-2-yl
18453,5-Cl2-Me2-Isoxazolin-3-yl0
pyridin-2-yl
18465-CF3-Me2-Isoxazolin-3-yl0
pyridin-2-yl
18473-CF3-Me2-Isoxazolin-3-yl0
pyridin-2-yl
18486-CF3-3-Cl-Me2-Isoxazolin-3-yl0
pyridin-2-yl
18495-CF3-3-Cl-Me2-Isoxazolin-3-yl0
pyridin-2-yl
1850Benzothiazol-Me2-Isoxazolin-3-yl0
2-yl
1851Benzoxazol-Me2-Isoxazolin-3-yl0
2-yl
1852Quinolin-2-ylMe2-Isoxazolin-3-yl0
18535-CF3-1,3,4-Me2-Isoxazolin-3-yl0
thiadiazol-2-yl
1854Pyrimidin-2-ylMe2-Isoxazolin-3-yl0
18556-Cl-pyrimidin-4-ylMe2-Isoxazolin-3-yl0
18565-Et-6-Me-Me2-Isoxazolin-3-yl0
pyrimidin-2-yl
18576-Cl-Me2-Isoxazolin-3-yl0
pyrazin-2-yl
18583,6-Me2-Me2-Isoxazolin-3-yl0
pyrazin-2-yl
18593-Ph-Me2-Isoxazolin-3-yl0
isoxazol-5-yl
18605-Me-Me2-Isoxazolin-3-yl0
isoxazol-3-yl
1861Pyridin-2-ylMe3-Me-isoxazol-5-yl0
18625-Cl-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
18633-Cl-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
18646-Cl-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
18653,5-Cl2-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
18665-CF3-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
18673-CF3-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
18686-CF3-3-Cl-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
18695-CF3-Cl-Me3-Me-isoxazol-5-yl0
pyridin-2-yl
1870Benzothiazol-Me3-Me-isoxazol-5-yl0
2-yl
1871Benzoxazol-Me3-Me-isoxazol-5-yl0
2-yl
1872Quinolin-2-ylMe3-Me-isoxazol-5-yl0
18735-CF31,3,4-Me3-Me-isoxazol-5-yl0
thiadiazol-2-yl
1874Pyrimidin-2-ylMe3-Me-isoxazol-5-yl0
18756-Cl-pyrimidin-4-ylMe3-Me-isoxazol-5-yl0
18765-Et-6-Me-Me3-Me-isoxazol-5-yl0
pyrimidin-2-yl
18776-Cl-Me3-Me-isoxazol-5-yl0
pyrazin-2-yl
18783,6-Me2-Me3-Me-isoxazol-5-yl0
pyrazin-2-yl
18793-Ph-Me3-Me-isoxazol-5-yl0
isoxazol-5-yl
18805-Me-Me3-Me-isoxazol-5-yl0
isoxazol-3-yl
1881Pyridin-2-ylMe1-Me-0
imidazol-2-yl
18825-Cl-Me1-Me-0
pyridin-2-ylimidazol-2-yl
18833-Cl-Me1-Me-0
pyridin-2-ylimidazol-2-yl
18846-Cl-Me1-Me-0
pyridin-2-ylimidazol-2-yl
18853,5-Cl2-Me1-Me-0
pyridin-2-ylimidazol-2-yl
18865-CF3-Me1-Me-0
pyridin-2-ylimidazol-2-yl
18873-CF3-Me1-Me-0
pyridin-2-ylimidazol-2-yl
18886-CF3-3-Cl-Me1-Me-0
pyridin-2-ylimidazol-2-yl
18895-CF3-3-Cl-Me1-Me-0
pyridin-2-ylimidazol-2-yl
1890Benzothiazol-Me1-Me-0
2-ylimidazol-2-yl
1891Benzoxazol-Me1-Me-0
2-ylimidazol-2-yl
1892Quinolin-2-ylMe1-Me-0
imidazol-2-yl
18935-CF3-1,3,4-Me1-Me-0
thiadiazol-2-ylimidazol-2-yl
1894Pyrimidin-2-ylMe1-Me-0
imidazol-2-yl
18956-Cl-pyrimidin-4-ylMe1-Me-0
imidazol-2-yl
18965-Et-6-Me-Me1-Me-0
pyrimidin-2-ylimidazol-2-yl
18976-Cl-Me1-Me-0
pyrazin-2-ylimidazol-2-yl
18983,6-Me2-Me1-Me-0
pyrazin-2-ylimidazol-2-yl
18993-Ph-Me1-Me-0
isoxazol-5-ylimidazol-2-yl
19005-Me-Me1-Me-0
isoxazol-3-ylimidazol-2-yl
1901Pyridin-2-ylMeIsoxazol-3-yl0
19025-Cl-MeIsoxazol-3-yl0
pyridin-2-yl
19033-Cl-MeIsoxazol-3-yl0
pyridin-2-yl
19046-Cl-MeIsoxazol-3-yl0
pyridin-2-yl
19053,5-Cl2-MeIsoxazol-3-yl0
pyridin-2-yl
19065-CF3-MeIsoxazol-3-yl0
pyridin-2-yl
19073-CF3-MeIsoxazol-3-yl0
pyridin-2-yl
19086-CF3-3-Cl-MeIsoxazol-3-yl0
pyridin-2-yl
19095-CF3-3-Cl-MeIsoxazol-3-yl0
pyridin-2-yl
1910Benzothiazol-MeIsoxazol-3-yl0
2-yl
1911Benzoxazol-MeIsoxazol-3-yl0
2-yl
1912Quinolin-2-ylMeIsoxazol-3-yl0
19135-CF3-1,3,4-MeIsoxazol-3-yl0
thiadiazol-2-yl
1914Pyrimidin-2-ylMeIsoxazol-3-yl0
19156-Cl-pyrimidin-4-ylMeIsoxazol-3-yl0
19165-Et-6-Me-MeIsoxazol-3-yl0
pyrimidin-2-yl
19176-Cl-MeIsoxazol-3-yl0
pyrazin-2-yl
19183,6-Me2-MeIsoxazol-3-yl0
pyrazin-2-yl
19193-Ph-MeIsoxazol-3-yl0
isoxazol-5-yl
19205-Me-MeIsoxazol-3-yl0
isoxazol-3-yl
1921Pyridin-2-ylMe5-Me-isoxazol-3-yl0
19225-Cl-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
19233-Cl-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
19246-Cl-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
19253,5-Cl2-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
19265-CF3-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
19273-CF3-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
19286-CF3-3-Cl-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
19295-CF3-3-Cl-Me5-Me-isoxazol-3-yl0
pyridin-2-yl
1930Benzothiazol-Me5-Me-isoxazol-3-yl0
2-yl
1931Benzoxazol-Me5-Me-isoxazol-3-yl0
2-yl
1932Quinolin-2-ylMe5-Me-isoxazol-3-yl0
19335-CF3-1,3,4-Me5-Me-isoxazol-3-yl0
thiadiazol-2-yl
1934Pyrimidin-2-ylMe5-Me-isoxazol-3-yl0
19356-Cl-pyrimidin-4-ylMe5-Me-isoxazol-3-yl0
19365-Et-6-Me-Me5-Me-isoxazol-3-yl0
pyrimidin-2-yl
19376-Cl-Me5-Me-isoxazol-3-yl0
pyrazin-2-yl
19383,6-Me2-Me5-Me-isoxazol-3-yl0
pyrazin-2-yl
19393-Ph-Me5-Me-isoxazol-3-yl0
isoxazol-5-yl
19405-Me-Me5-Me-isoxazol-3-yl0
isoxazol-3-yl
1941Pyridin-2-ylMe1,2,4-Oxadiazol-3-yl0
19425-Cl-Me1,2,4-Oxadiazol-3-yl0
pyridin-2-yl
19433-Cl-Me1,2,4-Oxadiazol-3-yl0
pyridin-2-yl
19446-Cl-Me1,2,4-Oxadiazol-3-yl0
pyridin-2-yl
19453,5-Cl2-Me1,2,4-Oxadiazol-3-yl0
pyridin-2-yl
19465-CF3-Me1,2,4-Oxadiazol-3-yl0
pyridin-2-yl
19473-CF3-Me1,2,4-Oxadiazol-3-yl0
pyridin-2-yl
19486-CF3-3-Cl-Me1,2,4-Oxadiazol-3-yl
pyridin-2-yl
19495-CF3-3-Cl-Me1,2,4-Oxadiazol-3-yl0
pyridin-2-yl
1950Benzothiazol-Me1,2,4-Oxadiazol-3-yl0
2-yl
1951Benzoxazol-Me1,2,4-Oxadiazol-3-yl0
2-yl
1952Quinolin-2-ylMe1,2,4-Oxadiazol-3-yl0
19535-CF3-1,3,4-Me1,2,4-Oxadiazol-3-yl0
thiadiazol-2-yl
1954Pyrimidin-2-ylMe1,2,4-Oxadiazol-3-yl0
19556-Cl-pyrimidin-4-ylMe1,2,4-Oxadiazol-3-yl0
19565-Et-6-Me-Me1,2,4-Oxadiazol-3-yl0
pyrimidin-2-yl
19576-Cl-Me1,2,4-Oxadiazol-3-yl0
pyrazin-2-yl
19583,6-Me2-Me1,2,4-Oxadiazol-3-yl0
pyrazin-2-yl
19593-Ph-Me1,2,4-Oxadiazol-3-yl0
isoxazol-5-yl
19605-Me-Me1,2,4-Oxadiazol-3-yl0
isoxazol-3-yl
1961Pyridin-2-ylMe5-Me-1,2,4-0
oxadiazol-3-yl
19625-Cl-Me5-Me-1,2,4-0
pyridin-2-yloxadiazol-3-yl
19633-Cl-Me5-Me-1 2,4-0
pyridin-2-yloxadiazol-3-yl
19646-Cl-Me5-Me-1,2,4-0
pyridin-2-yloxadiazol-3-yl
19653,5-Cl2-Me5-Me-1,2,4-0
pyridin-2-yloxadiazol-3-yl
19665-CF3-Me5-Me-1,2,4-0
pyridin-2-yloxadiazol-3-yl
19673-CF3-Me5-Me-1,2,4-0
pyridin-2-yloxadiazol-3-yl
19686-CF3-3-Cl-Me5-Me-1,2,4-0
pyridin-2-yloxadiazol-3-yl
19695-CF3-3-Cl-Me5-Me-1,2,4-0
pyridin-2-yloxadiazol-3-yl
1970Benzothiazol-Me5-Me-1,2,4-0
2-yloxadiazol-3-yl
1971Benzoxazol-Me5-Me-1,2,4-0
2-yloxadiazol-3-yl
1972Quinolin-2-ylMe5-Me-1,2,4-0
oxadiazol-3-yl
19735-CF3-1,3,4-Me5-Me-1,2,4-0
thiadiazol-2-yloxadiazol-3-yl
1974Pyrimidin-2-ylMe5-Me-1,2,4-0
oxadiazol-3-yl
19756-Cl-pyrimidin-4-ylMe5-Me-1,2,4-0
oxadiazol-3-yl
19765-Et-6-Me-Me5-Me-1,2,4-0
pyrimidin-2-yloxadiazol-3-yl
19776-Cl-Me5-Me-1,2,4-0
pyrazin-2-yloxadiazol-3-yl
19783,6-Me2-Me5-Me-1,2,4-0
pyrazin-2-yloxadiazol-3-yl
19793-Ph-Me5-Me-1,2,4-0
isoxazol-5-yloxadiazol-3-yl
19805-Me-Me5-Me-1,2,4-0
isoxazol-3-yloxadiazol-3-yl
1981Pyridin-2-ylMe1,3,4-Oxadiazol-2-yl0
19825-Cl-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
19833-Cl-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
19846-Cl-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
19853,5-Cl2-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
19865-CF3-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
19873-CF3-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
19886-CF3-3-Cl-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
19895-CF3-3-Cl-Me1,3,4-Oxadiazol-2-yl0
pyridin-2-yl
1990Benzothiazol-Me1,3,4-Oxadiazol-2-yl0
2-yl
1991Benzoxazol-Me1,3,4-Oxadiazol-2-yl0
2-yl
1992Quinolin-2-ylMe1,3,4-Oxadiazol-2-yl0
19935-CF3-1,3,4-Me1,3,4-Oxadiazol-2-yl0
thiadiazol-2-yl
1994Pyrimidin-2-ylMe1,3,4-Oxadiazol-2-yl0
19956-Cl-pyrimidin-4-ylMe1,3,4-Oxadiazol-2-yl0
19965-Et-6-Me-Me1,3,4-Oxadiazol-2-yl0
pyrimidin-2-yl
19976-Cl-Me1,3,4-Oxadiazol-2-yl0
pyrazin-2-yl
19983,6-Me2-Me1,3,4-Oxadiazol-2-yl0
pyrazin-2-yl
19993-Ph-Me1,3,4-Oxadiazol-2-yl0
isoxazol-5-yl
20005-Me-Me1,3,4-Oxadiazol-2-yl0
isoxazol-3-yl
2001C6H5Me2-Me-2H-1mp 63.0-66.0° C.
tetrazol-5-yl
20022-F—C6H4Me2-Me-2H-1
tetrazol-5-yl
20033-F—C6H4Me2-Me-2H-1
tetrazol-5-yl
20044-F—C6H4Me2-Me-2H-1
tetrazol-5-yl
20052-Cl—C6H4Me2-Me-2H-1mp 122-123° C.
tetrazol-5-yl
20063-Cl—C6H4Me2-Me-2H-1
tetrazol-5-yl
20074-Cl—C6H4Me2-Me-2H-1mp 120-121.5° C.
tetrazol-5-yl
20082-Br—C6H4Me2-Me-2H-1
tetrazol-5-yl
20093-Br—C6H4Me2-Me-2H-1
tetrazol-5-yl
20104-Br—C6H4Me2-Me-2H-1
tetrazol-5-yl
20113-I—C6H4Me2-Me-2H-1
tetrazol-5-yl
20122-Me—C6H4Me2-Me-2H-1mp 118-119° C.
tetrazol-5-yi1
20133-Me—C6H4Me2-Me-2H-1
tetrazol-5-yl
20144-Me—C6H4Me2-Me-2H-1mp 102.0-103.0° C.
tetrazol-5-yl
20152-Et—C6H4Me2-Me-2H-1
tetrazol-5-yl
20163-Et—C6H4Me2-Me-2H-1
tetrazol-5-yl
20174-Et—C6H4Me2-Me-2H-1
tetrazol-5-yl
20182-MeO—C6H4Me2-Me-2H-1
tetrazol-5-yl
20193-MeO—C6H4Me2-Me-2H-1
tetrazol-5-yl
20204-MeO—C6H4Me2-Me-2H-1
tetrazol-5-yl
20212-CF3—C6H4Me2-Me-2H-1
tetrazol-5-yl
20223-CF3—C6H4Me2-Me-2H-1
tetrazol-5-yl
20234-CF3—C6H4Me2-Me-2H-1
tetrazol-5-yl
20242,4-F2—C6H4Me2-Me-2H-1
tetrazol-5-yl
20252,5-F2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20262,6-F2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20273,4-F2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20283,5-F2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20292,3-Cl2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20302,4-Cl2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20312,5-Cl2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20323,4-Cl2—C6H3Me2-Me-2H-1mp 98-99° C.
tetrazol-5-yl
20333,5-Cl2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20342,3-Me2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20352,4-Me2—C6H3Me2-Me-2H-1
tetrazol-5-yt
20362,5-Me2—C6H3Me2-Me-2H-1mp 131-132° C.
tetrazol-5-yl
20373,4-Me2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20383,5-Me2—C6H3Me2-Me-2H-1
tetrazol-5-yl
20392-Cl-4-Me—C6H3Me2-Me-2H-1
tetrazol-5-yl
20402-Cl-5-Me—C6H3Me2-Me-2H-1
tetrazol-5-yl
20414-Cl-2-Me—C6H3Me2-Me-2H-1mp 135-136.5° C.
tetrazol-5-yl
20424-Cl-3-Me—C6H3Me2-Me-2H-1
tetrazol-5-yl
20433-Ph—C6H4Me2-Me-2H-1
tetrazol-5-yl
20444-Ph—C6H4Me2-Me-2H-1mp 108.0-110.0° C.
tetrazol-5-yl
20453-i-PrO—C6H4Me2-Me-2H-1
tetrazol-5-yl
20463-i-Pr—C6H4Me2-Me-2H-1
tetrazol-5-yl
20474-i-Pr—C6H4Me2-Me-2H-1
tetrazol-5-yl
20483-t-Bu—C6H4Me2-Me-2H-1
tetrazol-5-yl
20492-MeS—C6H4Me2-Me-2H-1
tetrazol-5-yl
20504-MeS—C6H4Me2-Me-2H-1
tetrazol-5-yl
20512,3,6-F3—C6H2Me2-Me-2H-1
tetrazol-5-yl
20522,4,5-Cl3—C6H2Me2-Me-2H-1
tetrazol-5-yl
20533-PhO—C6H4Me2-Me-2H-1
tetrazol-5-yl
20543,4,5-(MeO)3—C6H2Me2-Me-2H-1
tetrazol-5-yl
20552,3,5-Me3—C6H2Me2-Me-2H-1
tetrazol-5-yl
20563,4,5-Me3—C6H2Me2-Me-2H-1
tetrazol-5-yl
2057C6F5Me2-Me-2H-1
tetrazol-5-yl
20584-Cl-3-Et—C6H3Me2-Me-2H-1
tetrazol-5-yl
20593-EtO—C6H4Me2-Me-2H-1
tetrazol-5-yl
20604-EtO—C6H4Me2-Me-2H-1
tetrazol-5-yl
2061C6H5Me2-Me-2H-0
tetrazol-5-yl
20624-F—C6H4Me2-Me-2H-0
tetrazol-5-yl
20633-Cl—C6H4Me2-Me-2H-0
tetrazol-5-yl
20644-Cl—C6H4Me2-Me-2H-0
tetrazol-5-yl
20653-Me—C6H4Me2-Me-2H-0
tetrazol-5-yl
20664-Me—C6H4Me2-Me-2H-0
tetrazol-5-yl
20674-Et—C6H4Me2-Me-2H-0
tetrazol-5-yl
20684-NO2—C6H4Me2-Me-2H-0
tetrazol-5-yl
20693,4-Cl2—C6H3Me2-Me-2H-0
tetrazol-5-yl
20703,5-Cl2—C6H3Me2-Me-2H-0
tetrazol-5-yl
20713,4-Me2—C6H3Me2-Me-2H-0
tetrazol-5-yl
20723,5-Me2—C6H3Me2-Me-2H-0
tetrazol-5-yl
20733-PhO—C6H4Me2-Me-2H-0
tetrazol-5-yl
20744-Cl-3-Et—C6H3Me2-Me-2H-0
tetrazol-5-yl
20753-EtO—C6H4Me2-Me-2H-0
tetrazol-5-yl
20763-CF3—C6H4Me2-Me-2H-0
tetrazol-5-yl
20774-CF3—C6H4Me2-Me-2H-
tetrazol-5-yl
20783-i-PrO—C6H4Me2-Me-2H-0
tetrazol-5-yl
20793-i-Pr—C6H4Me2-Me-2H-0
tetrazol-5-yl
20804-Cl-3-Me—C6H3Me2-Me-2H-0
tetrazol-5-yl
2081Pyridin-2-ylMe2-Me-2H-1
tetrazol-5-yl
2082Pyridin-3-ylMe2-Me-2H-1
tetrazol-5-yl
20835-Cl-Me2-Me-2H-1
pyridin-2-yltetrazol-5-yl
20843-Cl-Me2-Me-2H-1
pyridin-2-yltetrazol-5-yl
20856-Cl-Me2-Me-2H-1
pyridin-2-yltetrazol-5-yl
20862-Cl-Me2-Me-2H-1
pyridin-3-yltetrazol-5-yl
20875-CF3-Me2-Me-2H-1
pyridin-2-yltetrazol-5-yl
20883-CF3-Me2-Me-2H-1
pyridin-2-yltetrazol-5-yl
20896-CF3-3-Cl-Me2-Me-2H-1
pyridin-2-yltetrazol-5-yl
20905-CF3-3-Cl-Me2-Me-2H-1
pyridin-2-yltetrazol-5-yl
2091Benzothiazol-Me2-Me-2H-1
2-yltetrazol-5-yl
2092Benzoxazol-Me2-Me-2H-1
2-yltetrazol-5-yl
2093Quinolin-2-ylMe2-Me-2H-1
tetrazol-5-yl
20945-CF3-1,3,4-Me2-Me-2H-1
thiadiazol-2-yttetrazol-5-yl
2095Pyrimidin-2-ylMe2-Me-2H-1
tetrazol-5-yl
20965-Cl-6-Me-Me2-Me-2H-1
pyrimidin-4-yltetrazol-5-yl
20975-Et-6-Me-Me2-Me-2H-1
pyrimidin-4-yltetrazol-5-yl
20986-Cl-Me2-Me-2H-1
pyrazin-2-yltetrazol-5-yl
20993,6-Me2-Me2-Me-2H-1
pyrazin-2-yltetrazol-5-yl
21005-Me-Me2-Me-2H-1
isoxazol-3-yltetrazol-5-yl
|
NoR1R3R4nPhysical data
|
2101C6H51,2,4-Oxadiazol-3-yl5-Cl1
21022-Cl—C6H41,2,4-Oxadiazol-3-yl5-Cl1
21032-Me—C6H41,2,4-Oxadiazol-3-yl5-Cl1
21042,5-Me2—C6H31,2,4-Oxadiazol-3-yl5-Cl1
21054-Cl-2-Me—C6H31,2,4-Oxadiazol-3-yl5-Cl1
21064-Cl—C6H41,2,4-Oxadiazol-3-yl5-Cl0
21074-Me—C6H41,2,4-Oxadiazol-3-yl5-Cl0
2108C6H51,2,4-Oxadiazol-3-yl5-Cl0
21095-CF3-1,2,4-Oxadiazol-3-yl5-Cl1
pyridin-2-yl
21105-CF3-1,2,4-Oxadiazol-3-yl5-Cl0
pyridin-2-yl
2111C6H55-Me-1,2,4-5-Cl1
oxadiazol-3-yl
21122-Cl—C6H45-Me-1,2,4-5-Cl1
oxadiazol-3-yl
21132-Me—C6H45-Me-1,2,4-5-Cl1
oxadiazol-3-yl
21142,5-Me2—C6H35-Me-1,2,4-5-Cl1
oxadiazol-3-yl
21154-Cl-2-Me—C6H35-Me-1,2,4-5-Cl1
oxadiazol-3-yl
21164-Cl—C6H45-Me-1,2,4-5-Cl0
oxadiazol-3-yl
21174-Me—C6H45-Me-1,2,4-5-Cl0
oxadiazol-3-yl
2118C6H55-Me-1,2,4-5-Cl0
oxadiazol-3-yl
21195-CF3-5-Me-1,2,4-5-Cl1
pyridin-2-yloxadiazol-3-y
21205-CF3-5-Me-1,2,4-5-Cl01H-NMR(CDCl3) δ ppm:
pyridin-2-yloxadiazol-3-yl2.46(3H, s), 4.03(3H, s),
6.77(1H, d, J=9.2), 7.16(1H, d,
J=9.2), 7.44-7.86(3H, m),
8.36(1H, d, J=1.8)
2121C6H5Isoxazol-3-yl5-Cl1
21222-Cl—C6H4Isoxazol-3-yl5-Cl1
21232-Me—C6H4Isoxazol-3-yl5-Cl1
21242,5-Me2—C6H3Isoxazol-3-yl5-Cl1
21254-Cl-2-Me—C6H3Isoxazol-3-yl5-Cl1
21264-Cl—C6H4Isoxazol-3-yl5-Cl0
21274-Me—C6H4Isoxazol-3-yl5-Cl0
2128C6H5Isoxazol-3-yl5-Cl0
21295-CF3-Isoxazol-3-yl5-Cl1
pyridin-2-yl
21305-CF3-Isoxazol-3-yl5-Cl0
pyridin-2-yl
2131C6H53-Me-5-Cl1
isoxazol-5-yl
21322-Cl—C6H43-Me-5-Cl1
isoxazol-5-yl
21332-Me—C6H43-Me-5-Cl1
isoxazol-5-yl
21342,5-Me2—C6H33-Me-5-Cl1
isoxazol-5-yl
21354-Cl-2-Me—C6H33-Me-5-Cl-1
isoxazol-5-yl
21364-Cl—C6H43-Me-5-Cl0
isoxazol-5-yl
21374-Me—C6H43-Me-5-Cl0
isoxazol-5-yl
2138C6H53-Me-5-Cl0
isoxazol-5-yl
21395-CF3-3-Me-5-Cl1
pyridin-2-ylisoxazol-5-yl
21405-CF3-3-Me-5-Cl0
pyridin-2-ylisoxazol-5-yl
2141C6H51-Me-imidazol-2-yl5-Cl1
21422-Cl—C6H41-Me-imidazol-2-yl5-Cl1
21432-Me—C6H41-Me-imidazol-2-yl5-Cl1
21442,5-Me2—C6H31-Me-imidazol-2-yl5-Cl1
21454-Cl-2-Me—C6H31-Me-imidazol-2-yl5-Cl1
21464-Cl—C6H41-Me-imidazol-2-yl5-Cl0
21474-Me—C6H41-Me-imidazol-2-yl5-Cl0
2148C6H51-Me-imidazol-2-yl5-Cl0
21495-CF3-1-Me-imidazol-2-yl5-Cl1
pyridin-2-yl
21505-CF3-1-Me-imidazol-2-yl5-Cl0
pyridin-2-yl
2151C6H51-Me-imidazol-2-yl5-F1
21522-Cl—C6H41-Me-imidazol-2-yl5-F1
21532-Me—C6H41-Me-imidazol-2-yl5-F1
21542,5-Me2—C6H31-Me-imidazol-2-yl5-F1
21554-Cl-2-Me—C6H31-Me-imidazol-2-yl5-F1
21564-Cl—C6H41-Me-imidazol-2-yl5-F0
21574-Me—C6H41-Me-imidazol-2-yl5-F0
2158C6H51-Me-imidazol-2-yl5-F0
21595-CF3-1-Me-imidazol-2-yl5-F1
pyridin-2-yl
21605-CF3-1-Me-imidazol-2-yl5-F0
pyridin-2-yl
2161C6H51,2,4-Oxadiazol-3-yl5-F1
21622-Cl—C6H41,2,4-Oxadiazol-3-yl5-F1
21632-Me—C6H41,2,4-Oxadiazol-3-yl5-F1
21642,5-Me2—C6H31,2,4-Oxadiazol-3-yl5-F1
21654-Cl-2-Me—C6H31,2,4-Oxadiazol-3-yl5-F1
21664-Cl—C6H41,2,4-Oxadiazol-3-yl5-F0
21674-Me—C6H41,2,4-Oxadiazol-3-yl5-F0
2168C6H51,2,4-Oxadiazol-3-yl5-F0
21695-CF3-1,2,4-Oxadiazol-3-yl5-F1
pyridin-2-yl
21705-CF3-1,2,4-Oxadiazol-3-yl5-F0
pyridin-2-yl
2171C6H55-Me-1,2,4-5-F1
oxadiazol-3-yl
21722-Cl—c6H45-Me-1,2,4-5-F1
oxadiazol-3-yl
21732-Me—C6H45-Me-1,2,4-5-F1
oxadiazol-3-yl
21742,5-Me2—C6H35-Me-1,2,4-5-F1
oxadiazoi-3-yl
21754-Cl-2-Me—C6H35-Me-1,2,4-5-F1
oxadiazol-3-yl
21764-Cl—C6H45-Me-1,2,4-5-F0
oxadiazol-3-yl
21774-Me—C6H45-Me-1,2,4-5-F0
oxadiazol-3-yi
2178C6H55-Me-1,2,4-5-F0
oxadiazol-3-yl
21795-CF3-5-Me-1,2,4-5-F1
pyridin-2-yloxadiazol-3-yl
21805-CF3-5-Me-1,2,4-5-F0
pyridin-2-yloxadiazol-3-yl
2181C6H5Isoxazol-3-yl5-F1
21822-Cl—C5H4Isoxazol-3-yl5-F1
21832-Me—C6H4Isoxazol-3-yl5-F1
21842,5-Me2—C6H3Isoxazol-3-yl5-F1
21854-Cl-2-Me—C6H3Isoxazol-3-yl5-F1
21864-Cl—C6H4Isoxazol-3-yl5-F0
21874-Me—C6H4Isoxazol-3-yl5-F0
2188C6H5Isoxazol-3-yl5-F0
21895-CF3-Isoxazol-3-yl5-F1
pyridin-2-yl
21905-CF3-Isoxazol-3-yl5-F1
pyridin-2-yl
2191C6H53-Me-5-F1
isoxazol-5-yl
21922-Cl—C6H43-Me-5-F1
isoxazol-5-yl
21932-Me—C6H43-Me-5-F1
isoxazol-5-yl
21942,5-Me2—C6H33-Me-5-F1
isoxazol-5-yl
21954-Cl-2-Me—C6H33-Me-5-F1
isoxazol-5-yl
21964-Cl—C6H43-Me-5-F0
Isoxazol-5-yl
21974-Me—C6H43-Me-5-F0
isoxazol-5-yl
2198C6H53-Me-5-F0
isoxazol-5-yl
21995-CF3-3-Me-5-F1
pyridin-2-ylisoxazol-5-yl
22005-CF3-3-Me-5-F0
pyridin-2-ylisoxazol-5-yl
2201C6H55-Me-1,3,4-H1
oxadiazol-2-yl
22022-Cl—C6H45-Me-1,3,4-H1
oxadiazol-2-yl
22034-Cl—C6H45-Me-1,3,4-H1
oxadiazol-2-yl
22042-Me—C6H45-Me-1,3,4-H1
oxadiazol-2-yl
22054-Me—C6H45-Me-1,3,4-H1
oxadiazol-2-yl
22063-CF3—C6H45-Me-1,3,4-H1
oxadiazol-2-yl
22072,5-Me2—C6H35-Me-1,3,4-H1mp 134.0-139.0° C.
oxadiazol-2-yl
22084-Cl-2-Me—C6H35-Me-1,3,4-H11H-NMR(CDCl3) δ ppm 2.12(3H,
oxadiazol-2-yls), 2.58(3H, s), 4.05(3H, s),
4.97(2H, s), 6.63(1H, d, J=8.5),
6.99-7.64(6H, m)
22092,5-Cl2—C6H35-Me-1,3,4-H1
oxadiazol-2-yl
22105-CF3-5-Me-1,3,4-H1
pyridin-2-yloxadiazol-2-yl
2211C6H5Thiazolidin-2-ylH1
22122-Cl—C6H4Thiazolidin-2-ylH1
22134-Cl—C6H4Thiazolidin-2-ylH1
22142-Me—C6H4Thiazolidin-2-ylH1
22154-Me—C6H4Thiazolidin-2-ylH1
22163-CF3—C6H4Thiazolidin-2-yl1I
22172,5-Me2—C6H3Thiazolidin-2-ylH11H-NMR(CDCl3) δ ppm 2.28(6H,
s), 2.40(1H, brs), 2.81-3.06(3H, m),
3.38-3.55(1H, m), 3.87(3H, s),
4.85-5.50(3H, m), 6.67-7.64(7H, m)
22184-Cl-2-Me—C6H3Thiazolidin-2-ylH1
22192,5-Cl2-—C6H3Thiazolidin-2-ylH1mp 121.0-122.0° C.
22205-CF3-Thiazolidin-2-ylH1
pyridin-2-yl
2221C6H53,5-Me2-H11H-NMR(CDCl3) δppm:
isoxazol-4-yl2.00(1.96)(3H, s), 2.17(3H, s),
3.94(3.91)(3H, s), 5.19(4.94)(2H,
s), 6.83-7.66(9H, m)
22222-Cl—C6H43,5-Me2-H1
isoxazol-4-yl
22234-Cl—C6H43,5-Me2-H1
isoxazol-4-yl
22242-Me—C6H43,5-Me2-H1
isaxazol-4-yl
22254-Me—C6H43,5-Me2-H1
isoxazol-4-yl
22263-CF3—C6H43,5-Me2-H1
isoxazol-4-yl
22272,5-Me2—C6H33,5-Me2-H11~NMR(CDCI3) 8 ppm:1.95-
isoxazol-4-yl2.28(12H, m), 3.94(3.99)(3H, s),
4.93(5.18)(2H, s), 6.57-7.71 (7H, m)
22284-Cl-2-Me—C6H33,5-Me2-H11H-NMR(CDCl3) δ ppm:
isoxazol-4-yl1.95(1.98)(3H, s), 2.13--2.23(6H,
m), 3.93(3.98)(3H, s),
4.91(5.17)(2H, s), 6.65-6.72(2H,
m), 7.01-7.66(5H, m)
22292,5-Cl2—C6H33,5-Me2-H1
isoxazol-4-yl
22305-CF3-3,5-Me2-H1
pyridin-2-ylisoxazol-4-yl
2231C6H51,3-Dioxolan-2-ylH1
22322-Cl—C6H41,3-Dioxolan-2-ylH1
22334-Cl—C6H41,3-Dioxolan-2-ylH1
22342-Me—C6H41,3-Dioxolan-2-ylH1
22354-Me—C6H41,3-Dioxolan-2-ylH1
22363-CF3—C6H41,3-Dioxolan-2-ylH1
22372,5-Me2—C6H31,3-Dioxolan-2-ylH11H-NMR(CDCl3) δ ppm 2.28(3H,
s), 2.29(3H, s), 3.59-3.85(4H, m),
3.92(3H, s), 5.04(1H, s), 5.09(1H,
s), 5.63(1H, s), 6.66-7.62(7H, m)
22384-Cl-2-Me—C6H31,3-Dioxolan-2-ylH1
22392,5-Cl2—C6H31,3-Dioxolan-2-ylH1
22405-CF3-1,3-Dioxolan-2-ylH1
pyridin-2-yl
2241C6H53-Me-2-isoxazolin-H1
5-yl
22422-Cl—C6H43-Me-2-isoxazolin-H1
5-yl
22434-Cl—C6H43-Me-2-isoxazolin-H1
5-yl
22442-Me—C6H43-Me-2-isoxazolin-H11H-NMR(CDCl3) δ ppm:
5-yl1.88(3H, s), 2.26(2.27)(3H, s),
2.84-3.38(2H, m), 3.95(3.87)(3H,
s), 4.87-5.38(2H, m), 5.74-
5.81(1H, m), 6.84-6.89(2H, m),
7.11-7.60(6H, m)
22454-Me—C6H43-Me-2-isoxazolin-H1
5-yl
22463-CF3—C6H43-Me-2-isoxazolin-H1
5-yl
22472,5-Me2—C6H33-Me-2-isoxazolin-H11~NMR(CDCI3) & ppm:
5-yl1.88(3H, s), 2.20(2.22)(3H, s),
2.30(3H, s), 2.84-3.37(2H, m),
3.96(3.88)(3H, s), 4.85-5.35(2H,
m), 5.74-5.82(1H, m), 6.67-
6.69(2H, m), 7.01(5H, m)
22484-Cl-2-Me—C6H33-Me-2-isoxazolin-H1
5-yl
22492,5-Cl2—C6H33-Me-2-isoxazolin-H1
5-yl
22505-CF3-3-Me-2-isoxazolin-H1
pyridin-2-yl5-yl
2251C6H54-Me-1,2,3-H1mp 90.5-91.5° C.
thiadiazol-5-yl
22522-Cl—C6H44-Me-1,2,3-H1
thiadiazol-5-yl
22534-Cl—C6H44-Me-1,2,3-H1
thiadiazol-5-yl
22542-Me—C6H44-Me-1,2,3-H1
thiadiazol-5-yl
22554-Me—C6H44-Me-1,2,3-H1
thiadiazol-5-yl
22563-CF3—C6H44-Me-1,2,3-H1
thiadiazol-5-yl
22572,5-Me2—C6H34-Me-1,2,3-H11H-NMR(CDCl3) δ ppm:
thiadiazol-5-yl2.01(3H, s), 2.14(3H, s),
2.25(3H, s), 4.18(3H, s),
4.98(2H, s), 6.51(1H, s),
6.65(1H, d, J=7.9), 6.96(1H, d,
J=7.3), 7.24-7.96(4H, m)
22584-Cl-2-Me—C6H34-Me-1,2,3-H1
thiadiazol-5-yl
22592,5-Cl2—C6H34-Me-1,2,3-H1
thiadiazol-5-yl
22605-CF3-4-Me-1,2,3-H1
pyridin-2-ylthiadiazol-5-yl
22613,5-Cl2-Isoxazol-3-ylH0
pyridin-2-yl
22623,5-Cl2-Isoxazol-5-yl H0
pyridin-2-yl
22633,5-Cl2-5-Me-H0
pyridin-2-ylisoxazol-3-yl
22643,5-Cl2-3-Me-H0
pyridin-2-ylisoxazol-5-yl
22653,5-Cl2-2-Isoxazolin-3-ylH0
pyridin-2-yl
22663,5-Cl2-5-Me-2-isoxazolin-H0
pyridin-2-yl3-yl
22673,5-Cl2-3-Me-2-isoxazolin-H0
pyridin-2-yl5-yl
22683,5-Cl2-2-FurylH0
pyridin-2-yl
22693,5-Cl2-Thiazolidin-2-ylH0
pyridin-2-yl
22703,5-Cl2-1-Me-H0
pyridin-2-ylimidazol-2-yl
22713,5-Cl2-1,2,4-Oxadiazol-H0
pyridin-2-yl3-yl
22723,5-Cl2-5-Me-1,2,4-H0
pyridin-2-yloxadiazol-3-yl
22733,5-Cl2-1,2,4-oxadiazol-5-ylH0
pyridin-2-yl
22743,5-Cl2-1,3,4-oxadiazol-2-ylH0
pyridin-2-yl
22753,5-Cl2-5-Me-1,3,4H0
pyridin-2-yloxadiazol-2-yl
22763,5-Cl2-Isoxazol-3-ylH1mp 136-137° C.
pyridin-2-yl
22773,5-Cl2-Isoxazol-5-ylH1
pyridin-2-yl
22783,5-Cl2-5-Me-H11H-NMR(CDCl3) δ ppm: 2.34(3H,
pyridin-2-ylisoxazol-3-yls), 3.97(3H, s), 5.32(2H, s),
6.36(1H, s), 7.24-7.85(6H, m).
22793,5-Cl2-3-Me-H1Isomer A: 1H-NMR(CDCl3) δ ppm:
pyridin-2-ylisoxazol-5-yl2.35(3H, s), 4.12(3H, s), 5.40(2H,
s), 6.95(1H, s), 7.37-7.86(6H, m)
Isomer B: 1H-NMR(CDCl3) δ ppm:
2.28(3H, s), 4.03(3H, s), 5.30(2H,
s), 6.01(1H, s), 7.21-7.86(6H, s)
22803,5-Cl2-2-Isoxazolin-3-ylH1
pyridin-2-yl
22813,5-Cl2-5-Me-2-H1
pyridin-2-ylisoxazolin-3-yl
22823,5-Cl2-3-Me-2-H1
pyridin-2-ylisoxazolin-5-yl
22833,5-Cl2-2-FurylH1
pyridin-2-yl
22843,5-Cl2-Thiazolidin-2-ylH1
pyridin-2-yl
22853,5-Cl2-1-Me-H1
pyridin-2-ylimidazol-2-yl
22863,5-Cl2-1,2,4-Oxadiazol-H1
pyridin-2-yl3-yl
22873,5-Cl2-5-Me-1,2,4-H1
pyridin-2-yloxadiazol-3-yl
22883,5-Cl2-1,2,4-Oxadiazol-H1
pyridin-2-yl5-yl
22893,5-Cl2-1,3,4-Oxadiazol-H1
pyridin-2-yl2-yl
22903,5-Cl2-5-Me-1,3,4-H1
pyridin-2-yloxadiazol-2-yl
22915-Cl-3-CF3-Isoxazol-3-ylH0
pyridin-2-yl
22925-Cl-3-CF3-Isoxazol-5-ylH0
pyridin-2-yl
22935-Cl-3-CF3-5-Me-H0
pyridin-2-ylisoxazol-3-yl
22945-Cl-3-CF3-3-Me-H0
pyridin-2-ylisoxazol-5-yl
22955-Cl-3-CF3-2-Isoxazolin-3-ylH0
pyridin-2-yl
22965-Cl-3-CF3-5-Me-2-isoxazolin-H0
pyridin-2-yl3-yl
22975-Cl-3-CF3-3-Me-2-isoxazolin-H0
pyridin-2-yl5-yl
22985-Cl-3-CF3-2-FurylH0
pyridin-2-yl
22995-Cl-3-CF3-Thiazolidin-2-ylH0
pyridin-2-yl
23005-Cl-3-CF3-1-Me-H0
pyridin-2-ylimidazol-2-ylH0
23015-Cl-3-CF3-1,2,4-Oxadiazol-H0
pyridin-2-yl3-yl
23025-Cl-3-CF3-5-Me-1,2,4-H0
pyridin-2-yloxadiazol-3-yl
23035-Cl-3-CF3-1,2,4-Oxadiazol-H0
pyridin-2-yl5-yl
23045-Cl-3-CF3-1,3,4-Oxadiazol-H0
pyridin-2-yl2-yl
23055-Cl-3-CF3-5-Me-1,3,4-H0
pyridin-2-yloxadiazol-2-yl
23065-Cl-3-CF3-Isoxazol-3-ylH1mp 97.5-98.5° C.
pyridin-2-yl
23075-Cl-3-CF3-Isoxazol-5-ylH1
pyridin-2-yl
23085-Cl-3-CF3-5-Me-H1mp 120-121° C.
pyridin-2-ylisoxazol-3-yl
23095-Cl-3-CF3-3-Me-H1Isomer A: 1H-NMR(CDCl3) δ ppm:
pyridin-2-ylisoxazol-5-yl2.37(3H, s), 4.14(3H, s), 5.45(2H,
s), 6.97(1H, s), 7.36-7.63(4H, m),
7.79(1H, d, J=2.4), 8.09(1H, d,
J=2.4)
Isomer B: 1H-NMR(CDCl3) δ ppm:
2.28(3H, s), 4.04(3H, s), 5.33(2H,
s), 6.01(1H, s), 7.20-7.65(4H, m),
7.80(1H, d, J=2.4), 8.08(1H, d,
J=2.4)
23105-Cl-3-CF3-2-Isoxazolin-3-ylH1
pyridin-2-yl
23115-Cl-3-CF3-5-Me-2-isoxazolin-H1
pyridin-2-yl3-yl
23125-Cl-3-CF3-3-Me-2-isoxazolin-H1
pyridin-2-yl5-yl
23135-Cl-3-CF3-2-FurylH1
pyridin-2-yl
23145-Cl-3-CF3-Thiazolidin-2-ylH1
pyridin-2-yl
23155-Cl-3-CF3-1-Me-H1
pyridin-2-ylimidazol-2-yl
23165-Cl-3-CF3-1,2,4-Oxadiazol-3-ylH1
pyridin-2-yl
23175-Cl-3-CF3-5-Me-1,2,4-H1
pyridin-2-yloxadiazol-3-yl
23185-Cl-3-CF3-1,2,4-Oxadiazol-5-ylH1
pyridin-2-yl
23195-Cl-3-CF3-1,3,4-Oxadiazol-2-ylH1
pyridin-2-yl
23205-Cl-3-CF3-5-Me-1,3,4-H1
pyridin-2-yloxadiazol-2-yl
|
NoR3R9R10Physical data
|
23211-Me-imidazol-2-yl2,4-F2—C6H3Me
23221-Me-imidazol-2-yl2,5-F2—C6H3Me
23231-Me-imidazol-2-yl3,4-F2—C6H3Me
23241-Me-imidazol-2-yl3,5-F2C6H3Me
23251-Me-imidazol-2-yl2,3-Cl2—C6H3Me
23261-Me-imidazol-2-yl2,4-Cl2—C6H3Me
23271-Me-imidazol-2-yl2,5-Cl2—C6H3Me
23281-Me-imidazol-2-yl3,4-Cl2—C6H3Me
23291-Me-imidazol-2-yl3,5-Cl2—C6H3Me
23301-Me-imidazol-2-yl3,4-Me2—C6H3Me
23311-Me-imidazol-2-yl2,4-Me2—C6H3Me
23321-Me-imidazol-2-yl3-Ph—C6H4Me
23331-Me-imidazol-2-yl4-Ph—C6H4Me
23341-Me-imidazol-2-ylMorpholinoMe
23351-Me-imidazol-2-yl2,6-Me2-Me
morpholino
23361-Me-imidazol-2-ylC6H5Et
23371-Me-imidazol-2-yl4-F—C6H4Et
23381-Me-imidazol-2-yl4-Cl—C6H4Et
23391-Me-imidazol-2-yl4-Me—C6H4Et
23401-Me-imidazol-2-yl3,4-Cl2—C6H3Et
23411H-1,2,4-C6H5Me
Triazol-1-yl
23421H-1,2,4-2-F—C6H4Me
Triazol-1-yl
23431H-1,2,4-3-F—C6H4Me
Triazol-1-yl
23441H-1,2,4-4-F—C6H4Me
Triazol-1-yl
23451H-1,2,4-2-Cl—C6H4Me
Triazol-1-yl
23461H-1,2,4-3-Cl—C6H4Me
Triazol-1-yl
23471H-1,2,4-4-Cl—C6H4Me
Triazol-1-yl
23481H-1,2,4-2-Br—C6H4Me
Triazol-1-yl
23491H-1,2,4-3-Br—C6H4Me
Triazol-1-yl
23501H-1,2,4-4-Br—C6H4Me
Triazol-1-yl
23511H-1,2,4-3-I—C6H4Me
Triazol-1-yl
23521H-1,2,4-2-Me-C6H4Me
Triazol-1-yl
23531H-1,2,4-3-Me—C6H4Me
Triazol-1-yl
23541H-1,2,4-4-Me—C6H4Me
Triazol-1-yl
23551H-1,2,4-3-Et—C6H4Me
Triazol-1-yl
23561H-1,2,4-4-Et—C6H4Me
Triazol-1-yl
23571H-1,2,4-3-MeO—C6H4Me
Triazol-1-yl
23581H-1,2,4-4-MeO—C6H4Me
Triazol-1-yl
23591H-1,2,4-3-CF3—C6H4Me
Triazol-1-yl
23601H-1,2,4-4-CF3—C6H4Me
Triazol-1-yl
23611H-1,2,4-2,4-F2—C6H3Me
Triazol-1-yl
23621H-1,2,4-2,5-F2—C6H3Me
Triazol-1-yl
23631H-1,2,4-3,4-F2—C6H3Me
Triazol-1-yl
23641H-1,2,4-3,5-F2—C6H3Me
Triazol-1-yl
23651H-1,2,4-2,3-Cl2—C6H3Me
Triazol-1-yl
23661H-1,2,4-2,4-Cl2—C6H3Me
Triazol-1-yl
23671H-1,2,4-2,5-Cl2—C6H3Me
Triazol-1-yl
23681H-1,2,4-3,4-Cl2—C6H3Me
Triazol-1-yl
23691H-1,2,4-3,5-Cl2—C6H3Me
Triazol-1-yl
23701H-1,2,4-3,4-Me2—C6H3Me
Triazol-1-yl
23711H-1,2,4-2,4-Me2—C6H3Me
Triazol-1-yl
23721H-1,2,4-3-Ph—C6H4Me
Triazol-1-yl
23731H-1,2,4-4-Ph—C6H4Me
Triazol-1-yl
23741H-1,2,4-MorpholinoMe
Triazol-1-yl
23751H-1,2,4-2,6-Me2-Me
Triazol-1-ylmorpholino
23761H-1,2,4-C6H5Et
Triazol-1-yl
23771H-1,2,4-4-F—C6H4Et
Triazol-1-yl
23781H-1,2,4-4-Cl—C6H4Et
Triazol-1-yl
23791H-1,2,4-4-Me—C6H4Et
Triazol-1-yl
23801H-1,2,4-3,4-Cl2-C6H3Et
Triazol-1-yl
2381Isoxazol-3-ylC6H5Me
2382Isoxazol-3-yl2-F—C6H4Me
2383Isoxazol-3-yl3-F—C6H4Me
2384Isoxazol-3-yl4-F—C6H4Me
2385Isoxazol-3-yl2-Cl—C6H4Me
2386Isoxazol-3-yl3-Cl—C6H4Me
2387Isoxazol-3-yl4Cl—C6H4Me1H-NMR(CDCl3) δ ppm: 2.04(3H, s),
4.00(3H, s), 5.13(2H, s), 6.74(1H, d,
J=1.7), 7.25-7.55(8H, m), 8.36(1H,
d, J=1.7)
2388Isoxazol-3-yl2-Br—C6H4Me
2389Isoxszol-3-yl3-Br—C6H4Me
2390Isoxazol-3-yl4-Br—C6H4Me
2391Isoxazol-3-yl3-I—C6H4Me
2392Isoxazol-3-yl2-Me—C6H4Me
2393Isoxazol-3-yl3-Me—C6H4Me
2394Isoxazol-3-yl4-Me—C6H4Me1H-NMR(CDCl3) δ ppm: 2.05(3H, s),
2.34(3H, s), 4.00(3H, s), 5.13(2H, s),
6.73(1H, d, J=1.7), 7.11-7.57(8H, m),
8.35(1H, d, J=1.7)
2395Isoxazol-3-yl3-Et—C6H4Me
2396Isoxazol-3-yl4-Et—C6H4Me
2397Isoxazol-3-yl3-MeO—C6H4Me
2398Isoxazol-3-yl4-MeO—C6H4Me1H-NMR(CDCl3) δ ppm: 2.05(3H, s),
3.81(3H, s), 4.00(3H, s), 5.12(2H, s),
6.73(1H, d, J=1.7), 6.82-6.86(2H, m),
7.25-7.56(6H, m), 8.35(1H, d, J=1.7)
2399Isoxazol-3-yl3-CF3—C6H4Me1H-NMR(CDCl3) δ ppm: 2.07(3H, s),
4.00(3H, s), 5.17(2H, s), 6.74(1H, d,
J=1.7). 7.26-7.74(7H, m), 7.82(1H, s),
8.36(1H, d, J=1.7)
2400Isoxazol-3-yl4-CF3—C6H4Me1H-NMR(CDCl3) δ ppm: 2.07(3H, s),
4.00(3H, s), 5.16(2H, s), 6.74(1H, d,
J=1.8), 7.26-7.67(8H, m), 8.36(1H, d,
J=1.8)
2401Isoxazol-3-yl2,4-F2—C6H3Me
2402Isoxazol-3-yl2,5-F2—C6H3Me
2403Isoxazol-3-yl3,4-F2—C6H3Me
2404Isoxazol-3-yl3,5-F2—C6H3Me
2405Isoxazol-3-yl2,3-Cl2—C6H3Me
2406Isoxazol-3-yl2,4-Cl2—C6H3Me
2407Isoxazol-3-yl2,5-Cl2—C6H3Me
2408Isoxazol-3-yl3,4-Cl2—C6H3Me1H-NMR(CDCl3) δ ppm: 2.01 (3H,
s), 4.00(3H, s), 5.14(2H, s),
6.75(1H, d, J=1.7), 7.25-7.65(7H,
m), 8.36(1H, d, J=1.7)
2409Isoxazol-3-yl3,5-Cl2—C6H3Me
2410Isoxazol-3-yl3,4-Me2—C6H3Me
2411Isoxazol-3-yl2,4-Me2—C6H3Me
2412Isoxazol-3-yl3-Ph—C6H4Me
2413Isoxazol-3-yl4-Ph—C6H4Me
2414Isoxazol-3-ylMorpholinoMe
2415Isoxazol-3-yl2,6-Me2-Me
morpholino
2416Isoxazol-3-ylC6H5Et
2417Isoxazol-3-yl4-F—C6H4Et
2418Isoxazol-3-yl4-Cl—C6H4Et
2419Isoxazol-3-yl4-Me—C6H4Et
2420Isoxazol-3-yl3,4-Cl2—C6H3Et
24215-Me-C6H5Me
isoxazol-3-yl
24225-Me-2-F—C6H4Me
isoxazol-3-yl
24235-Me-3-F—C6H4Me
isoxazol-3-yl
24245-Me-4-F—C6H4Me
isoxazol-3-yl
24255-Me-2-Cl—C6H4Me
isoxazol-3-yl
24265-Me-3-Cl—C6H4Me
isoxazol-3-yl
24275-Me-4-Cl—C6H4Me
isoxazol-3-yl
24285-Me-2-Br—C6H4Me
isoxazol-3-yl
24295-Me-3-Br—C6H4Me
isoxazol-3-yl
24305-Me-4-Br—C6H4Me
isoxazol-3-yl
24315-Me-3-I—C6H4Me
isoxazol-3-yl
24325-Me-2-Me—C6H4Me
isoxazol-3-yl
24335-Me-3-Me—C6H4Me
isoxazol-3-yl
24345-Me-4-Me—C6H4Me
isoxazol-3-yl
24355-Me-3-Et—C6H4Me
isoxazol-3-yl
24365-Me-4-Et—C6H4Me
isoxazol-3-yl
24375-Me-3-MeO—C6H4Me
isoxazol-3-yl
24385-Me-4-MeO—C6H4Me
isoxazol-3-yl
24395-Me-3-CF3—C6H4Me1H-NMR(CDCl3) δ ppm: 2.11(3H, s), 2.40(3H, s)
isoxazol-3-yl3.98(3H, s), 5.17(2H, s), 6.35(1H, d, J=0.7),
7.24-7.76(7H, m), 7.83(1H, s)
24405-Me-4-CF3—C6H4Me
isoxazol-3-yl
24415-Me-2,4-F2—C6H3Me
isoxazol-3-yl
24425-Me-2,5-F2—C6H3Me
isoxazol-3-yl
24435-Me-3,4-F2—C6H3Me
isoxazol-3-yl
24445-Me-3,5-F2—C6H3Me
isoxazol-3-yl
24455-Me-2,3-Cl2—C6H3Me
isoxazol-3-yl
24465-Me-2,4-Cl2—C6H3Me
isoxazol-3-yl
24475-Me-2,5-Cl2—C6H3Me
isoxazol-3-yl
24485-Me-3,4-Cl2—C6H3Me1H-NMR(CDCl3) δ ppm: 2.05(3H, s),
isoxazol-3-yl2.47(3H, s) 3.98(3H, s), 5.14(2H,
s), 6.35(1H, s), 7.23-7.53(6H, m),
7.66(1H, d, J=1.7)
24495-Me-3,5-Cl2—C6H3Me
isoxazol-3-yl
24505-Me-3,4-Me2—C6H3Me
isoxazol-3-yl
24515-Me-2,4-Me2—C6H3Me
isoxazol-3-yl
24525-Me-3-Ph—C6H4Me
isoxazol-3-yl
24535-Me-4-Ph—C6H4Me
isoxazol-3-yl
24545-Me-MorpholinoMe
isoxazol-3-yl
24555-Me-2,6-Me2-Me
isoxazol-3-ylmorpholino
24565-Me-C6H5Et
isoxazol-3-yl
24575-Me-4-F—C6H4Et
isoxazol-3-yl
24585-Me-4-Cl—C6H4Et
isoxazol-3-yl
24595-Me-4-Me—C6H4Et
isoxazol-3-yl
24605-Me-3,4-Cl2—C6H3Et
isoxazol-3-yl
2461Isoxazol-5-ylC6H5Me
2462Isoxazol-5-yl2-F—C6H4Me
2463Isoxazol-5-yl3-F—C6H4Me
2464Isoxazol-5-yl4-F—C6H4Me
2465Isoxazol-5-yl2-Cl—C6H4Me
2466Isoxazol-5-yl3-Cl—C6H4Me
2467Isoxazol-5-yl4-Cl—C6H4Me
2468Isoxazol-5-yl2-Br—C6H4Me
2469Isoxazol-5-yl3-Br—C6H4Me
2470Isoxazol-5-yl4-Br—C6H4Me
2471Isoxazol-5-yl3-I—C6H4Me
2472Isoxazol-5-yl2-Me—C6H4Me
2473Isoxazol-5-yl3-Me—C6H4Me
2474Isoxazol-5-yl4-Me—C6H4Me
2475Isoxazol-5-yl3-Et—C6H4Me
2476Isoxazol-5-yl4-Et—C6H4Me
2477Isoxazol-5-yl3-MeO—C6H4Me
2478Isoxazol-5-yl4-MeO—C6H4Me
2479Isoxazol-5-yl3-CF3—C6H4Me
2480Isoxazol-5-yl4-CF3—C6H4Me
2481Isoxazol-5-yl2,4-F2—C6H3Me
2482Isoxazol-5-yl2,5-F2C6H3Me
2483Isoxazol-5-yl3,4-F2—C6H3Me
2484Isoxazol-5-yl3,5-F2—C6H3Me
2485Isoxazol-5-yl2,3-Cl2—C6H3Me
2486Isoxazol-5-yl2,4-Cl2—C6H3Me
2487Isoxazol-5-yl2,5-Cl2—C6H3Me
2488Isoxazol-5-yl3,4-Cl2—C6H3Me
2489Isoxazol-5-yl3,5-Cl2—C6H3Me
2490Isoxazol-5-yl3,4-Me2—C6H3Me
2491Isoxazol-5-yl2,4-Me2—C6H3Me
2492Isoxazol-5-yl3-Ph—C6H4Me
2493Isoxazol-5-yl4-Ph—C6H4Me
2494Isoxazol-5-ylMorpholinoMe
2495Isoxazol-5-yl2,8-Me2-Me
morpholino
2496Isoxazol-5-ylC6H5Et
2497Isoxazol-5-yl4-F—C6H4Et
2498Isoxazol-5-yl4-Cl—C6H4Et
2499Isoxazol-5-yl4-Me—C6H4Et
2500Isoxazol-5-yl3,4-Cl2—C6H3Et
25013-Me-C6H5Me
isoxazol-5-yl
25023-Me-2-F—C6H4Me
isoxazol-5-yl
25033-Me-3-F—C6H4Me
isoxazol-5-yl
25043-Me-4-F—C6H4Me
isoxazol-5-yl
25053-Me-2-Cl—C6H4Me
isoxazol-5-yl
25063-Me-3-Cl—C6H4Me
isoxazol-5-yl
25073-Me-4-Cl—C6H4Me1H-NMR(CDCl3) δ
isoxazol-5-ylppm: 2.03(3H, S), 2.19(3H, S),
4.03(3H, S), 5.12(2H, S),
5.94(2H, S), 7.19-7.56(8H, m)
25083-Me-2-Br—C6H4Me
isoxazol-5-yl
25093-Me-3-Br—C6H4Me
isoxazol-5-yl
25103-Me-4-Br—C6H4Me
isoxazol-5-yl
25113-Me-3-I—C6H4Me
isoxazol-5-yl
25123-Me-2-Me—C6H4Me
isoxazol-5-yl
25133-Me-3-Me—C6H4Me
isoxazol-5-yl
25143-Me-4-Me—C6H4Me
isoxazol-5-yl
25153-Me-3-Et—C6H4Me
isoxazol-5-yl
25163-Me-4-Et—C6H4Me
isoxazol-5-yl
25173-Me-3-MeO—C6H4Me
isoxazol-5-yl
25183-Me-4-MeO—C6H4Me
isoxazol-5-yl
25193-Me-3-CF3—C6H4Me
isoxazol-5-yl
25203-Me-4-CF3—C6H4Me
isoxazol-5-yl
25213-Me-2,4-F2—C6H3Me
isoxazol-5-yl
25223-Me-2,5-F2—C6H3Me
isoxazol-5-yl
25233-Me-3,4-F2—C6H3Me
isoxazol-5-yl
25243-Me-3,5-F2—C6H3Me
isoxazol-5-yl
25253-Me-2,3-Cl—C6H3Me
isoxazol-5-yl
25263-Me-2,4-Cl2—C6H3Me
isoxazol-5-yl
25273-Me-2,5-Cl2—C6H3Me
isoxazol-5-yl
25283-Me-3,4-Cl2—C6H3Memp 84.0-85.0° C.
isoxazol-5-yl
25293-Me-3,5-Cl2—C6H3Me
isoxazol-5-yl
25303-Me-3,4-Me2—C6H3Me
isoxazol-5-yl
25313-Me-2,4-Me2—C6H3Me
isoxazol-5-yl
25323-Me-3-Ph—C6H4Me
isoxazol-5-yl
25333-Me-4-Ph—C6H4Me
isoxazol-5-yl
25343-Me-MorpholinoMe
isoxazol-5-yl
25353-Me-2,6-Me2-Me
isoxazol-5-ylmorpholino
25363-Me-C6H5Et
isoxazol-5-yl
25373-Me-4-F—C6H4Et
isoxazol-5-yl
25383-Me-4-Cl—C6H4Et
isoxazol-5-yl
25393-Me-4-Me—C6H4Et
isoxazol-5-yl
25403-Me-3,4-Cl2—C6H3Et
isoxazol-5-yl
25411,3,4-Oxadiazol-C6H5Me
2-yl
25421,3,4-Oxadiazol-2-F—C6H4Me
2-yl
25431,3,4-Oxadiazol-3-F—C6H4Me
2-yl
25441,3,4-Oxadiazol-4-F—C6H4Me
2-yl
25451,3,4-Oxadiazol-2-Cl—C6H4Me
2-yl
25461,3,4-Oxadiazol-3-Cl—C6H4Me
2-yl
25471,3,4-Oxadiazol-4-Cl—C6H4Me
2-yl
25481,3,4-Oxadiazol-2-Br—C6H4Me
2-yl
25491,3,4-Oxadiazol-3-Br—C6H4Me
2-yl
25501,3,4-Oxadiazol-4-Br—C6H4Me
2-yl
25511,3,4-Oxadiazol-3-I—C6H4Me
2-yl
25521,3,4-Oxadiazol-2-Me—C6H4Me
2-yl
25531,3,4-Oxadiazol-3-Me—C6H4Me
2-yl
25541,3,4-Oxadiazol-4-Me—C6H4Me
2-yl
25551,3,4-Oxadiazol-3-Et—C6H4Me
2-yl
25561,3,4-Oxadiazol-4-Et—C6H4Me
2-yl
25571,3,4-Oxadiazol-3-MeO—C6H4Me
2-yl
25581,3,4-Oxadiazol-4-MeO—C6H4Me
2-yl
25591,3,4-Oxadiazol-3-CF3—C6H4Me
2-yl
25601,3,4-Oxadiazol-4-CF3—C6H4Me
2-yl
25611,3,4-Oxadiazol-2,4-F2—C6H3Me
2-yl
25621,3,4-Oxadiazol-2,5-F2—C6H3Me
2-yl
25631,3,4-Oxadiazol-3,4-F2—C6H3Me
2-yl
25641,3,4-Oxadiazol-3,5-F2—C6H3Me
2-yl
25651,3,4-Oxadiazol-2,3-Cl2—C6H3Me
2-yl
25661,3,4-Oxadiazol-2,4-Cl2—C6H3Me
2-yl
25671,3,4-Oxadiazol-2,5-Cl2—C6H3Me
2-yl
25681,3,4-Oxadiazol-3,4-Cl2—C6H3Me
2-yl
25691,3,4-Oxadiazol-3,5-Cl2—C6H3Me
2-yl
25701,3,4-Oxadiazol-3,4-Me2—C6H3Me
2-yl
25711,3,4-Oxadiazol-2,4-Me2—C6H3Me
2-yl
25721,3,4-Oxadiazol-3-Ph—C6H4Me
2-yl
25731,3,4-Oxadiazol-4-Ph—C6H4Me
2-yl
25741,3,4-Oxadiazol-MorpholinoMe
2-yl
25751,3,4-Oxadiazol-2,6-Me2-Me
2-ylmorpholino
25761,3,4-Oxadiazol-C6H5Et
2-yl
25771,3,4-Oxadiazol-4-F—C6H4Et
2-yl
25781,3,4-Oxadiazol-4-Cl—C6H4Et
2-yl
25791,3,4-Oxadiazol-4-Me—C6H4Et
2-yl
25801,3,4-Oxadiazol-3,4-Cl2—C6H3Et
2-yl
25815-Me-1,3,4-C6H5Me
oxadiazol-2-yl
25825-Me-1,3,4-2-F—C6H4Me
oxadiazol-2-yl
25835-Me-1,3,4-3-F—C6H4Me
oxadiazol-2-yl
25845-Me-1,3,4-4-F—C6H4Me
oxadiazol-2-yl
25855-Me-1,3,4-2-Cl—C6H4Me
oxadiazol-2-yl
25865-Me-1,3,4-3-Cl—C6H4Me
oxadiazol-2-yl
25875-Me-1,3,4-4-Cl—C6H4Me
oxadiazol-2-yl
25885-Me-1,3,4-2-Br—C6H4Me
oxadiazol-2-yl
25895-Me-1,3,4-3-Br—C6H4Me
oxadiazol-2-yl
25905-Me-1,3,4-4-Br—C6H4Me
oxadiazol-2-yl
25915-Me-1,3,4-3-I—C6H4Me
oxadiazol-2-yl
25925-Me-1,3,4-2-Me—C6H4Me
oxadiazol-2-yl
25935-Me -1,3,4-3-Me—C6H4Me
oxadiazol-2-yl
25945-Me-1,3,4-4-Me—C6H4Me
oxadiazol-2-yl
25955-Me-1,3,4-3-Et—C6H4Me
oxadiazol-2-yl
25965-Me-1,3,4-4-Et—C6H4Me
oxadiazol-2-yl
25975-Me-1,3,4-3-MeO—C6H4Me
oxadiazol-2-yl
25985-Me-1,3,4-4-MeO—C6H4Me
oxadiazol-2-yl
25995-Me-1,3,4-3-CF3—C6H4Me
oxadiazol-2-yl
26005-Me-1,3,4-4-CF3—C6H4Me
oxadiazol-2-yl
26015-Me-1,3,4-2,4-F2—C6H3Me
oxadiazol-2-yl
26025-Me-1,3,4-2,5-F2—C6H3Me
oxadiazol-2-yl
26035-Me-1,3,4-3,4-F2—C6H3Me
oxadiazol-2-yl
26045-Me-1,3,4-3,5-F2—C6H3Me
oxadiazol-2-yl
26055-Me-1,3,4-2,3-Cl2—C6H3Me
oxadiazol-2-yl
26065-Me-1,3,4-2,4-Cl2—C6H3Me
oxadiazol-2-yl
26075-Me-1,3,4-2,5-Cl2—C6H3Me
oxadiazol-2-yl
26085-Me-1,3,4-3,4-Cl2—C6H3Me
oxadiazol-2-yl
26095-Me-1,3,4-3,5-Cl2—C6H3Me
oxadiazol-2-yl
26105-Me-1,3,4-3,4-Me2—C6H3Me
oxadiazol-2-yl
26115-Me-1,3,4-2,4-Me2—C6H3Me
oxadiazol-2-yl
26125-Me-1,3,4-3-Ph—C6H4Me
oxadiazol-2-yl
26135-Me-1,3,4-4-Ph—C6H4Me
oxadiazol-2-yl
26145-Me-1,3,4-MorpholinoMe
oxadiazol-2-yl
26155-Me-1,3,4-2,6-Me2-Me
oxadiazoi-2-ylmorpholino
26165-Me-1,3,4-C6H5Et
oxadiazol-2-yl
26175-Me-1,3,4-4-F—C6H4Et
oxadiazol-2-yl
26185-Me-1,3,4-4-Cl—C6H4Et
oxadiazol-2-yl
26195-Me-1,3,4-4-Me—C6H4Et
oxadiazol-2-yl
26205-Me-1,3,4-3,4-Cl2—C6H3
oxadiazol-2-yl
2621Oxazol-5-ylC6H5Memp 92.0-93.5° C.
2622Oxazol-5-yl2-F—C6H4Me
2623Oxazol-5-yl3-F—C6H4Me
2624Oxazol-5-yl4-F—C6H4Me
2625Oxazol-5-yl2-Cl—C6H4Me
2626Oxazol-5-yl3-Cl—C6H4Me
2627Oxazol-5-yl4-Cl—C6H4Me1H-NMR(CDCl3) δ ppm:
2.02(3H, S), 4.01(3H, S),
5.14(2H, S), 6.82(1H, S), 7.21-
7.58(8H, m), 7.90(1H, S)
2628Oxazol-5-yl2-Br—C6H4Me
2629Oxazol-5-yl3-Br—C6H4Me
2630Oxazol-5-yl4-Br—C6H4Me
2631Oxazol-5-yl3-I—C6H4Me
2632Oxazol-5-yl2-Me—C6H4Me
2633Oxazol-5-yl3-Me—C6H4Me
2634Oxazol-5-yl4-Me—C6H4Me
2635Oxazol-5-yl3-Et—C6H4Me
2636Oxazol-5-yl4-Et—C6H4Me
2637Oxazol-5-yl3-MeO—C6H4Me
2638Oxazol-5-yl4-MeO—C6H4Me
2639Oxazol-5-yl3-CF3—C6H4Me1H-NMR(CDCl3) δ ppm:
2.06(3H, S), 4.01(3H, S),
5.17(2H, S), 6.83(1H, S), 7.22-
7.26(1H, m), 7.38-7.59(5H, m),
7.72(1H, d, j=7.9), 7.81(1H, S),
7.91(1H, S)
2640Oxazol-5-yl4-CF3—C6H4Me
2641Oxazol-5-yl2,4-F2—C6H3Me
2642Oxazol-5-yl2,5-F2—C6H3Me
2643Oxazol-5-yl3,4-F2—C6H3Me
2644Oxazol-5-yl3,5-F2—C6H3Me
2645Oxazol-5-yl2,3-Cl2—C6H3Me
2646Oxazol-5-yl2,4-Cl2—C6H3Me1H-NMR(CDCl3) δ ppm:
2.02(3H, S), 4.00(3H, S),
5.13(2H, S), 6.85(1H, S), 7.13-
7.58(7H, m)7.91(1H, S)
2647Oxazol-5-yl2,5-Cl2—C6H3Me
2648Oxazol-5-yl3,4-Cl2—C6H3Memp 94.0-95.0° C.
2649Oxazol-5-yl3,5-Cl2—C6H3Me
2650Oxazol-5-yl3,4-Me2—C6H3Me
2651Oxazol-5-yl2,4-Me2—C6H3Me
2652Oxazol-5-yl3-Ph—C6H4Me
2653Oxazol-5-yl4-Ph—C6H4Me
2654Oxazol-5-ylMorpholinoMe
2655Oxazol-5-yl2,6-Me2-Me
morpholino
2656Oxazol-5-ylC6H5Et
2657Oxazol-5-yl4-F—C6H4Et
2658Oxazol-5-yl4-Cl—C6H4Et
2659Oxazol-5-yl4-Me—C6H4Et
2660Oxazol-5-yl3,4-Cl2—C6H3Et
26615-Me-1,2,4-C6H5Me1H-NMR(CDCl3) δ
oxadiazol-3-ylppm: 2.11(3H, s), 2.95(3H, s),
4.08(3H, s), 5.16(2H, s),
7.26-7.58(9H, m)
26625-Me-1,2,4-2-F—C6H4Me
oxadiazol-3-yl
26635-Me-1,2,4-3-F—C6H4Me
oxadiazol-3-yl
26645-Me-1,2,4-4-F—C6H4Me
oxadiazol-3-yl
26655-Me-1,2,4-2-Cl—C6H4Me
oxadiazol-3-yl
26665-Me-1,2,4-3-Cl—C6H4Me
oxadiazol-3-yl
26675-Me-1,2,4-4-Cl—C6H4Me
oxadiazol-3-yl
26685-Me-1,2,4-2-Br—C6H4Me
oxadiazol-3-yl
26695-Me-1,2,4-3-Br—C6H4Me
oxadiazol-3-yl
26705-Me-1,2,4-4-Br—C6H4Me
oxadiazol-3-yl
26715-Me-1,2,4-3-I—C6H4Me
oxadiazol-3-yl
26725-Me-1,2,4-2-Me—C6H4Me
oxadiazol-3-yl
26735-Me-1,2,4-3-Me—C6H4Me
oxadiazol-3-yl
26745-Me-1,2,4-4-Me—C6H4Me
oxadiazol-3-yl
26755-Me-1,2,4-3-Et—C6H4Me
oxadiazol-3-yl
26765-Me-1,2,4-4-Et—C6H4Me
oxadiazol-3-yl
26775-Me-1,2,4-3-MeO—C6H4Me
oxadiazol-3-yl
26785-Me-1,2,4-4-MeO—C6H4Me
oxadiazol-3-yl
26795-Me-1,2,4-3-CF3—C6H4Me
oxadiazol-3-yl
26805-Me-1,2,4-4-CF3—C6H4Me
oxadiazol-3-yl
26815-Me-1,2,4-2,4-F2—C6H3Me
oxadiazol-3-yl
26825-Me-1,2,4-2,5-F2—C6H3Me
oxadiazol-3-yl
26835-Me-1,2,4-3,4-F2—C6H3Me
oxadiazol-3-yl
26845-Me-1,2,4-3,5-F2—C6H3Me
oxadiazol-3-yl
26855-Me-1,2,4-2,3-Cl2—C6H3Me
oxadiazol-3-yl
26865-Me-1,2,4-2,4-Cl2—C6H3Me
oxadiazol-3-yl
26875-Me-1,2,4-2,5-Cl2—C6H3Me
oxadiazol-3-yl
26885-Me-1,2,4-3,4-Cl2—C6H3Me
oxadiazol-3-yl
26895-Me-1,2,4-3,5-Cl2—C6H3Me
oxadiazol-3-yl
26905-Me-1,2,4-3,4-Me2—C6H3Me
oxadiazol-3-yl
26915-Me-1,2,4-2,4-Me2—C6H3Me
oxadiazol-3-yl
26925-Me-1,2,4-3-Ph—C6H4Me
oxadiazol-3-yl
26935-Me-1,2,4-4-Ph—C6H4Me
oxadiazol-3-yl
26945-Me-1,2,4-MorpholinoMe
oxadiazol-3-yl
26955-Me-1,2,4-2,6-Me2-Me
oxadiazol-3-ylmorpholino
26965-Me-1,2,4-C6H5Et
oxadiazol-3-yl
26975-Me-1,2,4-4-F—C6H4Et
oxadiazol-3-yl
26985-Me-1,2,4-4-Cl—C6H4Et
oxadiazol-3-yl
26995-Me-1,2,4-4-Me—C6H4Et
oxadiazol-3-yl
27005-Me-1,2,4-3,4-Cl2—C6H3Et
oxadiazol-3-yl
27011-Me-1H-C6H5Memp 119-120° C.
tetrazol-5-yl
27021-Me-1H-2-F—C6H4Me
tetrazol-5-yl
27031-Me-1H-3-F—C6H4Me
tetrazol-5-yl
27041-Me-1H-4-F—C6H4Me
tetrazol-5-yl
27051-Me-1H-2-Cl—C6H4Me
tetrazol-5-yl
27061-Me-1H-3-Cl—C6H4Me
tetrazol-5-yl
27071-Me-1H-4-Cl—C6H4Me
tetrazol-5-yl
27081-Me-1H-2-Br—C6H4Me
tetrazol-5-yl
27091-Me-1H-3-Br—C6H4Me
tetrazol-5-yl
27101-Me-1H-4-Br—C6H4Me
tetrazol-5-yl
27111-Me-1H-3-I—C6H4Me
tetrazol-5-yl
27121-Me-1H-2-Me—C6H4Me
tetrazol-5-yl
27131-Me-1H-3-Me—C6H4Me
tetrazol-5-yl
27141-Me-1H-4-Me—C6H4Me
tetrazol-5-yl
27151-Me-1H-3-Et—C6H4Me
tetrazol-5-yl
27161-Me-1H-4-Et—C6H4Me
tetrazol-5-yl
27171-Me-1H-3-MeO—C6H4Me
tetrazol-5-yl
27181-Me-1H-4-MeO—C6H4Me
tetrazol-5-yl
27191-Me-1H-3-CF3—C6H4Me
tetrazol-5-yl
27201-Me-1H-4-CF3—C6H4Me
tetrazol-5-yl
27211-Me-1H-2,4-F2—C6H3Me
tetrazol-5-yl
27221-Me-1H-2,5-F2—C6H3Me
tetrazol-5-yl
27231-Me-1H-3,4-F2—C6H3Me
tetrazol-5-yl
27241-Me-1H-3,5-F2—C6H3Me
tetrazol-5-yl
27251-Me-1H-2,3-Cl2—C6H3Me
tetrazol-5-yl
27261-Me-1H-2,4-Cl2—C6H3Me
tetrazol-5-yl
27271-Me-1H-2,5-Cl2—C6H3Me
tetrazol-5-yl
27281-Me-1H-3,4-Cl2—C6H3Me
tetrazol-5-yl
27291-Me-1H-3,5-Cl2—C6H3Me
tetrazol-5-yl
27301-Me-1H-3,4-Me2—C6H3Me
tetrazol-5-yl
27311-Me-1H-2,4-Me2—C6H3Me
tetrazol-5-yl
27321-Me-1H-3-Ph—C6H4Me
tetrazol-5-yl
27331-Me-1H-4-Ph—C6H4Me
tetrazol-5-yl
27341-Me-1H-morpholinoMe
tetrazol-5-yl
27351-Me-1H-2,6-Me2-Me
tetrazol-5-ylmorpholino
27361-Me-1H-C6H5Et
tetrazol-5-yl
27371-Me-1H-4-F—C6H4Et
tetrazol-5-yl
27381-Me-1H-4-Cl—C6H4Et
tetrazol-5-yl
27391-Me-1H-4-Me—C6H4Et
tetrazol-5-yl
27401-Me-1H-3,4-Cl2—C6H3Et
tetrazol-5-yl
27412-Me-2H-C6H5Memp 96-98° C.
tetrazol-5-yl
27422-Me-2H-2-F—C6H4Me
tetrazol-5-yl
27432-Me-2H-3-F—C6H4Me
tetrazol-5-yl
27442-Me-2H-4-F—C6H4Me
tetrazol-5-yl
27452-Me-2H-2-Cl—C6H4Me
tetrazol-5-yl
27462-Me-2H-3-Cl—C6H4Me
tetrazol-5-yl
27472-Me-2H-4-Cl—C6H4Me
tetrazol-5-yl
27482-Me-2H-2-Br—C6H4Me
tetrazol-5-yl
27492-Me-2H-3-Br—C6H4Me
tetrazol-5-yl
27502-Me-2H-4-Br—C6H4Me
tetrazol-5-yl
27512-Me-2H-3-I—C6H4Me
tetrazol-5-yl
27522-Me-2H-2-Me—C6H4Me
tetrazol-5-yl
27532-Me-2H-3-Me—C6H4Me
tetrazol-5-yl
27542-Me-2H-4-Me—C6H4Me
tetrazol-5-yl
27552-Me-2H-3-Et—C6H4Me
tetrazol-5-yl
27562-Me-2H-4-Et-C6H4Me
tetrazol-5-yl
27572-Me-2H-3-MeO—C6H4Me
tetrazol-5-yl
27582-Me-2H-4-MeO—C6H4Me
tetrazol-5-yl
27592-Me-2H-3-CF3—C6H4Me
tetrazol-5-yl
27602-Me-2H-4-CF3—C6H4Me
tetrazol-5-yl
27612-Me-2H-2,4-F2—C6H3Me
tetrazol-5-yl
27622-Me-2H-2,5-F2—C6H3Me
tetrazol-5-yl
27632-Me-2H-3,4-F2—C6H3Me
tetrazol-5-yl
27642-Me-2H-3,5-F2—C6H3Me
tetrazol-5-yl
27652-Me-2H-2,3-Cl2—C6H3Me
tetrazol-5-yl
27662-Me-2H-2,4-Cl2—C6H3Me
tetrazol-5-yl
27672-Me-2H-2,5-Cl2—C6H3Me
tetrazol-5-yl
27682-Me-2H-3,4-Cl2—C6H3Me
tetrazol-5-yl
27692-Me-2H-3,5-Cl2—C6H3Me
tetrazol-5-yl
27702-Me-2H-3,4-Me2—C6H3Me
tetrazol-5-yl
27712-Me-2H-2,4-Me2—C6H3Me
tetrazol-5-yl
27722-Me-2H-3-Ph—C6H4Me
tetrazol-5-yl
27732-Me-2H-4-Ph—C6H4Me
tetrazol-5-yl
27742-Me-2H-MorpholinoMe
tetrazol-5-yl
27752-Me-2H-2,6-Me2-
tetrazol-5-ylmorpholino
27762-Me-2H-C6H5Et
tetrazol-5-yl
27772-Me-2H-4-F—C6H4Et
tetrazol-5-
27782-Me-2H-4-Cl—C6H4Et
tetrazol-5-yl
27792-Me-2H-4-Me—C6H4Et
tetrazol-5-yl
27802-Me-2H-3,4-Cl2—C6H3Et
tetrazol-5-yl
2781Thiazolidin-2-ylC6H5Me
2782Thiazolidin-2-yl2-F—C6H4Me
2783Thiazolidin-2-yl3-F—C6H4Me
2784Thiazolidin-2-yl4-F—C6H4Me
2785Thiazolidin-2-yl2-Cl—C6H4Me
2786Thiazoiidin-2-yl3-Cl—C6H4Me
2787Thiazolidin-2-yl4-Cl—C6H4Me
2788Thiazolidin-2-yl2-Br—C6H4Me
2789Thiazolidin-2-yl3-Br—C6H4Me
2790Thiazolidin-2-yl4-Br—C6H4Me
2791Thiazolidin-2-yl3-I—C6H4Me
2792Thiazolidin-2-yl2-Me—C6H4Me
2793Thiazolidin-2-yl3-Me—C6H4Me
2794Thiazolidin-2-yl4-Me—C6H4Me
2795Thiazolidin-2-yl3-Et—C6H4Me
2796Thiazolidin-2-yl4-Et—C6H4Me
2797Thiazolidin-2-yl3-MeO—C6H4Me
2798Thiazolidin-2-yl4-MeO—C6H4Me
2799Thiazolidin-2-yl3-CF3—C6H4Me1H-NMR(CDCl3) δ ppm:
2.39(3H, S), 2.75-3.10(3H,
m)3.50(2H, m), 3.86(3H, S),
5.20-5.30(2H, m), 5.30-
5.50(1H, m), 7.37-7.61(6H,
m),7.82(1H, j=7.9),
7.91(1H, S)
2800Thiazolidin-2-yl4-CF3—C6H4Me
2801Thiazolidin-2-yl2,4-F2—C6H3Me
2802Thiazolidin-2-yl2,5-F2—C6H3Me
2803Thiazolidin-2-yl3,4-F2—C6H3Me
2804Thiazolidin-2-yl3,5-F2—C6H3Me
2805Thiazolidin-2-yl2,3-Cl2—C6H3Me
2806Thiazolidin-2-yl2,4-Cl2—C6H3Me
2807Thiazolidin-2-yl2,5-Cl2—C6H3Me
2808Thiazolidin-2-yl3,4-Cl2—C6H3Me
2809Thiazolidin-2-yl3,5-Cl2—C6H3Me
2810Thiazolidin-2-yl3,4-Me2—C6H3Me
2811Thiazolidin-2-yl2,4-Me2—C6H3Me
2812Thiazolidin-2-yl3-Ph—C6H4Me
2813Thiazolidin-2-yl4-Ph—C6H4Me
2814Thiazolidin-2-ylMorpholinoMe1H-NMR(CDCl3) δ ppm:
1.98(3H, S), 2.70-2.80(1H, m),
2.89-3.06(2H, m), 3.10(4H, t
j=4.9), 3.4-3.5(2H, m), 3.69(4H,
tj=4.9), 3.83(3H, S), 4.91(2H, S),
5.40(1H, S)7.33-7.55(4H, m)
2815Thiazolidin-2-yl2,6-Me2-Me
morpholino
2816Thiazolidin-2-ylC6H5Et
2817Thiazolidin-2-yl4-F—C6H4Et
2818Thiazolidin-2-yl4-Cl—C6H4Et
2819Thiazolidin-2-yl4-Me—C6H4Et
2820Thiazolidin-2-yl3,4-Cl2—C6H3Et
28213-Me-thiazolidin-C6H5Me
2-yl
28223-Me-thiazolidin-2-F—C6H4Me
2-yl
28233-Me-thiazolidin-3-F—C6H4Me
2-yl
28243-Me-thiazolidin-4-F—C6H4Me
2-yl
28253-Me-thiazolidin-2-Cl—C6H4Me
2-yl
28263-Me-thiazolidin-3-Cl—C6H4Me
2-yl
28273-Me-thiazolidin-4-Cl—C6H4Me
2-yl
28283-Me-thiazolidin-2-Br—C6H4Me
2-yl
28293-Me-thiazolidin-3-Br—C6H4Me
2-yl
28303-Me-thiazolidin-4-Br—C6H4Me
2-yl
28313-Me-thiazolidin-3-I—C6H4Me
2-yl
28323-Me-thiazolidin-2-Me—C6H4Me
2-yl
28333-Me-thiazolidin-3-Me—C6H4Me
2-yl
28343-Me-thiazolidin-4-Me—C6H4Me
2-yl
28353-Me-thiazolidin-3-Et—C6H4Me
2-yl
28363-Me-thiazolidin-4-Et—C6H4Me
2-yl
28373-Me-thiazolidin-3-MeO—C6H4Me
2-yt
28383-Me-thiazolidin-4-MeO—C6H4Me
2-yl
28393-Me-thiazolidin-3-CF3—C6H4Me1H-NMR(CDCl3) δ ppm:
2-yl2.31(3H, d j=3.7), 2.47(3H, d
j=14.7), 2.83-3.25(4H, m),
3.84(3H, S), 4.94((1H, d j=54.9),
5.14-5.35(2H, m), 7.19-
7.80(6H, m), 7.83(1H, d j=7.9),
7.93(1H, S)
28403-Me-thiazolidin-4-CF3—C6H4Me
2-yl
28413-Me-thiazolidin-2,4-F2—C6H3Me
2-yl
28423-Me-thiazolidin-2,5-F2—C6H3Me
2-yl
28433-Me-thiazolidin-3,4-F2—C6H3Me
2-yl
28443-Me-thiazolidin-3,5-F2—C6H3Me
2-yl
28453-Me-thiazolidin-2,3-Cl2—C6H3Me
2-yl
28463-Me-thiazolidin-2,4-Cl2—C6H3Me
2-yl
28473-Me-thiazolidin-2,5-Cl2—C6H3Me
2-yl
28483-Me-thiazolidin-3,4-Cl2—C6H3Me
2-yl
28493-Me-thiazolidin-3,5-Cl2—C6H3Me
2-yl
28503-Me-thiazolidin-3,4-Me2—C6H3Me
2-yl
28513-Me-thiazolidin-2,4-Me2—C6H3Me
2-yl
28523-Me-thiazolidin-3-Ph—C6H4Me
2-yl
28533-Me-thiazolidin-4-Ph—C6H4Me
2-yl
28543-Me-thiazolidin-MorpholinoMe
2-yl
28553-Me-thiazolidin-2,6-Me2-Me
2-ylmorpholino
28563-Me-thiazolidin-C6H5Et
2-yl
28573-Me-thiazolidin-4-F—C6H4Et
2-yl
28583-Me-thiazolidin-4-Cl—C6H4Et
2-yl
28593-Me-thiazolidin-4-Me—C6H4Et
2-yl
28603-Me-thiazolidin-3,4-Cl2—C6H3Et
2-yl
28612-Isoxazolin-3-ylC6H5Me
28622-Isoxazolin-3-yl2-F—C6H4Me
28632-Isoxazolin-3-yl3-F—C6H4Me
28642-Isoxazolin-3-yl4-F—C6H4Me
28652-Isoxazolin-3-yl2-Cl—C6H4Me
28662-Isoxazolin-3-yl3-Cl—C6H4Me
28672-Isoxazolin-3-yl4-Cl—C6H4Me
28682-Isoxazolin-3-yl2-Br—C6H4Me
28692-Isoxazolin-3-yl3-Br—C6H4Me
28702-Isoxazolin-3-yl4-Br—C6H4Me
28712-Isoxazolin-3-yl3-I—C6H4Me
28722-Isoxazolin-3-yl2-Me—C6H4Me
28732-Isoxazolin-3-yl3-Me—C6H4Me
28742-Isoxazolin-3-yl4-Me—C6H4Me
28752-Isoxazolin-3-yl3-Et—C6H4Me
28762-Isoxazolin-3-yl4-Et—C6H4Me
28772-Isoxazolin-3-yl3-MeO—C6H4Me
28782-Isoxazolin-3-yl4-MeO—C6H4Me
28792-Isoxazolin-3-yl3-CF3—C6H4Me
28802-Isoxazolin-3-yl4-CF3—C6H4Me
28812-Isoxazolin-3-yl2,4-F2—C6H3Me
28822-Isoxazolin-3-yl2,5-F2—C6H3Me
28832-Isoxazolin-3-yl3,4-F2—C6H3Me
28842-Isoxazolin-3-yl3,5-F2—C6H3Me
28852-Isoxazolin-3-yl2,3-Cl2—C6H3Me
28862-Isoxazolin-3-yl2,4-Cl2—C6H3Me
28872-Isoxazolin-3-yl2,5-Cl2—C6H3Me
28882-Isoxazolin-3-yl3,4-Cl2—C6H3Me
28892-Isoxazolin-3-yl3,5-Cl2—C6H3Me
28902-Isoxazolin-3-yl3,4-Me2—C6H3Me
28912-Isoxazolin-3-yl2,4-Me2—C6H3Me
28922-Isoxazolin-3-yl3-Ph—C6H4Me
28932-Isoxazolin-3-yl4-Ph—C6H4Me
28942-Isoxazolin-3-ylMorpholinoMe
28952-Isoxazolin-3-yl2,6-Me2-Me
morpholino
28962-Isoxazolin-3-ylC6H5Et
28972-Isoxazolin-3-yl4-F—C6H4Et
28982-Isoxazolin-3-yl4-Cl—C6H4Et
28992-Isoxazolin-3-yl4-Me—C6H4Et
29002-Isoxazolin-3-yl3,4-Cl2—C6H3Et
29015-Me-2-C6H5Me
isoxazolin-3-yl
29025-Me-2-2-F—C6H4Me
isoxazolin-3-yl
29035-Me-2-3-F—C6H4Me
isoxazolin-3-yl
29045-Me-2-4-F—C6H4Me
isoxazolin-3-yl
29055-Me-2-2-Cl—C6H4Me
isoxazolin-3-yl
29065-Me-2-3-Cl—C6H4Me
isoxazolin-3-yl
29075-Me-2-4-Cl—C6H4Me
isoxazolin-3-yl
29085-Me-2-2-Br—C6H4Me
isoxazolin-3-yl
29095-Me-2-3-Br—C6H4Me
isoxazolin-3-yl
29105-Me-2-4-Br—C6H4Me
isoxazolin-3-yl
29115-Me-2-3-I—C6H4Me
isoxazolin-3-yl
29125-Me-2-2-Me—C6H4Me
isoxazolin-3-yl
29135-Me-2-3-Me—C6H4Me
isoxazolin-3-yl
29145-Me-2-4-Me—C6H4Me
isoxazolin-3-yl
29155-Me-2-3-Et—C6H4Me
isoxazolin-3-yl
29165-Me-2-4-Et—C6H4Me
isoxazolin-3-yl
29175-Me-2-3-MeO—C6H4Me
isoxazolin-3-yl
29185-Me-2-4-MeO—C6H4Me
isoxazolin-3-yl
29195-Me-2-3-CF3—C6H4Me
isoxazolin-3-yl
29205-Me-2-4-CF3—C6H4Me
isoxazolin-3-yl
29215-Me-2-2,4-F2—C6H3Me
isoxazolin-3-yl
29225-Me-2-2,5-F2—C6H3Me
isoxazolin-3-yl
29235-Me-2-3,4-F2—C6H3Me
isoxazolin-3-yl
29245-Me-2-3,5-F2—C6H3Me
isoxazolin-3-yl
29255-Me-2-2,3-Cl2—C6H3Me
isoxazolin-3-yl
29265-Me-2-2,4-Cl2—C6H3Me
isoxazolin-3-yl
29275-Me-2-2,5-Cl2—C6H3Me
isoxazolin-3-yl
29285-Me-2-3,4-Cl2—C6H3Me
isoxazolin-3-yl
29295-Me-2-3,5-Cl2—C6H3Me
isoxazolin-3-yl
29305-Me-2-3,4-Me—C6H3Me
isoxazolin-3-yl
29315-Me-2-2,4-Me2—C6H3Me
isoxazolin-3-yl
29325-Me-2-3-Ph—C6H4Me
isoxazolin-3-yl
29335-Me-2-4-Ph—C6H4Me
isoxazolin-3-yl
29345-Me-2-MorpholinoMe
isoxazolin-3-yl
29355-Me-2-2,6-Me2-Me
isoxazolin-3-ylmorpholino
29365-Me-2-C6H5Et
isoxazolin-3-yl
29375-Me-2-4-F—C6H4Et
isoxazolin-3-yl
29385-Me-2-4-Cl—C6H4Et
isoxazolin-3-yl
29395-Me-2-4-Me—C6H4Et
isoxazolin-3-yl
29405-Me-2-3,4-Cl2—C6H3Et
isoxazolin-3-yl
2941Imidazol-1-ylC6H5H1H-NMR(CDCl3) δ ppm:
4.04(3H, S), 5.18(2H, S),
7.03(1H, S), 7.15-7.17(1H, m),
7.29-7.65(9H, m), 7.90(1H, S),
8.05(1H, S)
2942Imidazol-1-yl4-F—C6H4H
2943Imidazol-1-yl4-Cl—C6H4Hmp 92.5-93.0° C.
2944Imidazol-1-yl4-Me—C6H4H
2945Imidazol-1-yl3,4-Cl2—C6H3H
29461-Me-imidazol-2-ylC6H5H
29471-Me-imidazol-2-yl4-F—C6H4H
29481-Me-imidazol-2-yl4-Cl—C6H4H
29491-Me-imidazol-2-yl4-Me—C6H4H
29501-Me-imidazol-2-yl3,4-Cl2—C6H3H
29511,2,4-Triazol-1-ylC6H5Hmp 76.5-77.5° C.
29521,2,4-Triazol-1-yl4-F—C6H4H
29531,2,4-Triazol-1-yl4-Cl—C6H4H
29541,2,4-Triazol-1-yl4-Me—C6H4H
29551,2,4-Triazol-1-yl3,4-Cl2—C6H3H
29565-Me-1,2,4-C6H5H
oxadiazol-3-yl
29575-Me-1,2,4-4-F—C6H4H
oxadiazol-3-yl
29585-Me-1,2,4-4-Cl—C6H4H
oxadiazol-3-yl
29595-Me-1,2,4-4-Me—C6H4H
oxadiazol-3-yl
29605-Me-1,2,4-3,4-Cl2—C6H3H
oxadiazol-3-yl
2961Isoxazol-3-ylC6H5H
2962Isoxazol-3-yl4-F—C6H4H
2963Isoxazol-3-yl4-Cl—C6H4H
2964Isoxazol-3-yl4-Me—C6H4H
2965Isoxazol-3-yl3,4-Cl2—C6H3H
29665-Me-C6H5H
isoxazol-3-yl
29675-Me-4-F—C6H4
isoxazol-3-yl
29685-Me-4-Cl—C6H4H
isoxazol-3-yl
29695-Me-4-Me—C6H4H
isoxazol-3-yl
29705-Me-3,4-Cl2—C6H3H
isoxazol-3-yl
2971Isoxazol-5-ylC6H5H
2972Isoxazol-5-yl4-F—C6H4H
2973Isoxazol-5-yl4-Cl—C6H4H
2974Isoxazol-5-yl4-Me—C6H4H
2975Isoxazol-5-yl3,4-Cl2—C6H3H
29763-Me-C6H5H
isoxazol-5-yl
29773-Me-4-F—C6H4H
isoxazoi-5-yl
29783-Me-4-Cl—C6H4H
isoxazol-5-yl
29793-Me-4-Me—C6H4H
isoxazol-5-yl
29803-Me-3,4-Cl2—C6H3H
isoxazot-5-yl
2981Oxazol-5-ylC6H5Hmp 77-78.5° C.
2982Oxazol-5-yl4-F—C6H4H
2983Oxazol-5-yl4-Cl—C6H4H
2984Oxazol-5-yl4-Me—C6H4H
2985Oxazol-5-yl3,4-Cl2—C6H3H
29862-Isoxazolin-3-ylC6H5H
29872-Isoxazolin-3-yl4-F—C6H4H
29882-Isoxazolin-3-yl4-Cl—C6H4H
29892-Isoxazolin-3-yl4-Me—C6H4H
29902-Isoxazolin-3-yl3,4-Cl2—C6H3H
2991Thiazolidin-2-ylC6H5H
2992Thiazolidin-2-yl4-F—C6H4H
2993Thiazolidin-2-yl4-Cl—C6H4H
2994Thiazolidin-2-yl4-Me—C6H4H
2995Thiazolidin-2-yl3,4-Cl2—C6H3H
29963-Me-thiazolidin-C6H5H
2-yl
29973-Me-thiazolidin-4-F—C6H4H
2-yl
29983-Me-thiazolidin-4-Cl—C6H4H
2-yl
29993-Me-thiazolidin-4-Me—C6H4H
2-yl
30003-Me-thiazolidin-3,4-Cl2—C6H3H
2-yl
3001Oxazol-4-ylC6H5Memp 94.5-96.0° C.
3002Oxazol-4-yl4-F—C6H4Me
3003Oxazol-4-yl4-Cl—C6H4Me1H-NMR(CDCl3) δ ppm:
2.04(3H, S), 4.14(3H, S),
5.22(2H, S), 7.27-7.56(8H, m),
7.77(1H, S), 7.97(1H, S)
3004Oxazol-4-yl4-Me—C6H4Me
3005Oxazol-4-yl3,4-Cl2—C6H3Me1H-NMR(CDCl3) δ ppm:
2.01(3H, S), 4.15(3H, S),
5.24(2H, S), 5.50-7.62(6H, m),
7.66(1H, tj=1.2), 7.76(1H, S).
7.97(1H, S)
3006Oxazol-4-ylC6H5Hmp 97-98° C.
3007Oxazol-4-yl4-Cl—C6H4H
3008Oxazol-4-ylC6H5Et
3009Oxazol-4-yl4-Cl—C6H4Et
3010Oxazol-4-yl3,4-Cl2—C6H3Et
30111-Me-1H-C6H5Memp 119-120° C.
tetrazol-5-yl
30121-Me-1H-4-F—C6H4Me
tetrazol-5-yl
30131-Me-1H-4-Cl—C6H4Me
tetrazol-5-yl
30141-Me-1H-4-Me—C6H4Me
tetrazol-5-yl
30151-Me-1H-3,4-Cl2—C6H3Me
tetrazol-5-yl
3016Oxazol-4-yl3-CF3—C6H4Me1H-NMR(CDCl3) δ ppm:
2.07(3H, S), 4.15(3H, S),
5.26(2H, S), 7.35-7.77(8H, m),
7.82(1H, S), 7.97(1H, S)
30171-Me-1H-4-Cl—C6H4H
tetrazol-5-yl
30181-Me-1H-C6H5Et
tetrazol-5-yl
30191-Me-1H-4-Cl—C6H4Et
tetrazol-5-yl
3020Oxazol-4-yl2,4-Cl2—C6H3Me1H-NMR(CDCl3) δ ppm:
2.04(3H, S), 4.14(3H, S),
5.22(2H, S), 7.13-7.56(7H, m),
7.78(1H, S), 7.98(1H, S)
30211,2,4-Oxadiazol-C6H5Me
5-yl
30221,2,4-Oxadiazol-4-F—C6H4Me
5-yl
30231,2,4-Oxadiazol-4-Cl—C6H4Me
5-yl
30241,2,4-Oxadiazol-4-Me—C6H4Me
5-yl
30251,2,4-Oxadiazol-3,4-Cl2—C6H3Me
5-yl
30261,2,4-Oxadiazol-C6H5Hmp 1201-121° C.
5-yl
30271,2,4-Oxadiazol-4-Cl—C6H4H
5-yl
30281,2,4-Oxadiazol-C6H5Et
5-yl
30291,2,4-Oxadiazol-4-Cl—C6H4Et
5-yl
30301,2,4-Oxadiazol-3,4-Cl2—C6H3Et
5-yl
30311-Me-1,2,4-C6H5Me
triazol-5-yl
30321-Me-1,2,4-4-F—C6H4Me
triazol-5-yl
30331-Me-1,2,4-4-Cl—C6H4Me
triazol-5-yl
30341-Me-1,2,4-4-Me—C6H4Me
triazol-5-yl
30351-Me-1,2,4-3,4-Cl2—C6H3Me
triazol-5-yl
30361-Me-1,2,4-C6H5H1H-NMR(CDCl3) δ ppm:
triazol-5-yl4.03(3H, S), 4.12(3H, S),
5.07(2H, S), 7.27-7.55(9H,
m), 7.79(1H, S), 7.80(1H, S)
30371-Me-1,2,4-4-Cl—C6H4H
triazol-5-yl
30381-Me-1,2,4-C6H5Et
triazol-5-yl
30391-Me-1,2,4-4-Cl—C6H4Et
triazol-5-yl
30401-Me-1,2,4-3,4-Cl2—C6H3Et
triazol-5-yl
3041Imidazol-1-ylC6H5Me1H-NMR(CDCl3) δ
ppm: 2.09(3H, s), 4.03(3H, s),
5.28(2H, s), 7.01(1H, s),
7.14(1H, d, J=2.4), 7.30-
7.62(9H, m), m), 8.03(1H, s)
3042Imidazol-1-yl2-F—C6H4Me
3043Imidazol-1-yl3-F—C6H4Me
3044Imidazol-1-yl4-F—C6H4Me
3045Imidazol-1-yl2-Cl—C6H4Me
3046Imidazol-1-yl3-Cl—C6H4Me
3047Imidazol-1-yl4-Cl—C6H4Me1H-NMR(CDCl3) δ
ppm: 2.07(3H, s), 4.06(3H, s),
5.18(2H, s), 7.01-7.52(10H, m),
8.01(1H, s)
3048Imidazol-1-yl2-Br—C6H4Me
3049Imidazol-1-yl3-Br—C6H4Me
3050Imidazoi-1-yl4-Br—C6H4Me
3051Imidazol-1-yl3-I—C6H4Me
3052Imidazol-1-yl2-Me—C6H4Me
3053Imidazol-1-yl3-Me—C6H4Me
3054Imidazol-1-yl4-Me—C6H4Me
3055Imidazol-1-yl3-Et—C6H4Me
3056Imidazol-1-yl4-Et—C6H4Me
3057Imidazol-1-yl3-MeO—C6H4Me
3058Imidazol-1-yl4-MeO—C6H4Me
3059Imidazol-1-yl3-CF3—C6H4Me1H-NMR(CDCl3) δ ppm: 2.09(3H,
s), 4.04(3H, s), 5.22(2H, s),
7.01(1H, d, J=1.2), 7.15(1 H, d,
J=1.2), 7.35-7.85(8H, m),
8.02(1H, s)
3060Imidazol-1-yl4-CF3—C6H4Me
3061Imidazol-1-yl2,4-F2—C6H3Me
3062Imidazol-1-yl2,5-F2—C6H3Me
3063Imidazol-1-yl3,4-F2—C6H3Me
3064Imidazol-1-yl3,5-F2—C6H3Me
3065Imidazol-1-yl2,3-Cl2—C6H3Me
3066Imidazol-1-yl2,4-Cl2—C6H3Me1H-NMR(CDCl3) δ ppm: 2.06(3H,
s), 4.03(3H, s), 5.16(2H, s),
7.02(1H, s), 7.13-7.52(8H, m),
8.01(1H, s)
3067Imidazol-1-yl2,5-Cl2—C6H3Me
3068Imidazol-1-yl3,4-Cl2—C6H3Me1H-NMR(CDCl3) δ ppm: 2.03(3H,
s), 4.04(3H, s), 5.19(2H, s),
7.01(1H, s), 7.13-7.52(7H, m),
7.66(1H, s), 8.01(1H, s)
3069Imidazol-1-yl3,5-Cl2—C6H3Me
3070Imidazol-1-yl3,4-Me2—C6H3Me
3071Imidazol-1-yl2,4-Me2—C6H3Me
3072Imidazol-1-yl3-Ph—C6H4Me
3073Imidazol-1-yl4-Ph—C6H4Me
3074Imidazol-1-ylMorpholinoMe
3075Imidazol-1-yl2,6-Me2-Me
morpholino
3076Imidazol-1-ylC6H5Et
3077Imidazol-1-yl4-F—C6H4Et
3078Imidazol-1-yl4-Cl—C6H4Et
3079Imidazol-1-yl4-Me—C6H4Et
3080Imidazol-1-yl3,4-Cl2—C6H3Et
30811-Me-imidazol-2-ylC6H5Me
30821-Me-imidazol-2-yl2-F—C6H4Me
30831-Me-imidazol-2-yl3-F—C6H4Me
30841-Me-imidazol-2-yl4-F—C6H4Me
30851-Me-imidazol-2-yl2-Cl—C6H4Me
30861-Me-imidazol-2-yl3-Cl—C6H4Me
30871-Me-imidazol-2-yl4-Cl—C6H4Me
30881-Me-imidazol-2-yl2-Br—C6H4Me
30891-Me-imidazol-2-yl3-Br—C6H4Me
30901-Me-imidazol-2-yl4-Br—C6H4Me
30911-Me-imidazol-2-yl3-I—C6H4Me
30921-Me-imidazol-2-yl2-Me—C6H4Me
30931-Me-imidazol-2-yl3-Me—C6H4Me
30941-Me-imidazol-2-yl4-Me—C6H4Me
30951-Me-imidazol-2-yl3-Et—C6H4Me
30961-Me-imidazol-2-yl4-Et—C6H4Me
30971-Me-imidazol-2-yl3-MeO—C6H4Me
30981-Me-imidazol-2-yl4-MeO—C6H4Me
30991-Me-imidazol-2-yl3-CF3—C6H4Me
31001-Me-imidazol-2-yl4-CF3—C6H4Me
3101Imidazol-1-ylMeMe1H-NMR(CDCl3) δ
ppm: 1.70(3H, s), 1.78(3H, s),
4.03(3H, s), 5.01(2H, s),
7.02(1H, s), 7.16(1H, d,
J=1.2), 7.31-7.49(4H, m),
7.99(1H, s)
3102Imidazol-1-ylCyclohexylMe
3103Imidazol-1-ylt-BuMe
3104Imidazol-1-yl5-Me-Me
isoxazol-3-yl
3105Imidazol-1-ylPyridin-3-ylMe
31061-Me-imidazol-2-ylMeMe
31071-Me-imidazol-2-ylCyclohexylMe
31081-Me-imidazol-2-ylt-BuMe
31091-Me-imidazol-2-yl5-Me-Me
isoxazol-3-yl
31101-Me-imidazol-2-ylPyridin-3-ylMe
3111Isoxazol-3-ylMeMe
3112Isoxazol-3-ylCyclohexylMe
3113Isoxazol-3-ylt-BuMe
3114Isoxazol-3-yl5-Me-Me
isoxazol-3-yl
3115Isoxazol-3-ylPyridin-3-ylMe
31165-Me-MeMe
isoxazol-3-yl
31175-Me-CyclohexylMe
isoxazol-3-yl
31185-Me-t-BuMe
isoxazol-3-yl
31195-Me-5-Me-Me
isoxazol-3-ylisoxazol-3-yl
31205-Me-Pyridin-3-ylMe
isoxazol-3-yl
31213-Me-MeMe
isoxazol-5-yl
31223-Me-CyclohexylMe
isoxazol-5-yl
31233-Me-t-BuMe
isoxazol-5-yl
31243-Me-5-Me-Me
isoxazol-5-ylisoxazol-3-yl
31253-Me-Pyridin-3-ylMe
isoxazol-5-yl
31261,3,4-Oxadiazol-MeMe
2-yl
31271,3,4-Oxadiazol-CyclohexylMe
2-yl
31281,3,4-Oxadiazol-t-BuMe
2-yl
31291,3,4-Oxadiazol-5-Me-Me
2-ylisoxazol-3-yl
31301,3,4-Oxadiazol-Pyridin-3-ylMe
2-yl
3131Thiazolidin-2-ylMeMe
3132Thiazolidin-2-ylCyclohexylMe
3133Thiazolidin-2-ylt-BuMe
3134Thiazolidin-2-yl5-Me-Me
isoxazol-3-yl
3135Thiazolidin-2-ylPyridin-3-ylMe
3136Pyrazol-1-ylC6H5H1H-NMR(CDCl3) δ
ppm: 4.03(3H, s), 4.93(2H, s),
6.43(1H, t, J=2.4), 7.31-
7.60(10H, m), 7.99(1H, s),
8.51(1H, d, J=2.4)
3137Pyrazol-1-ylC6H5Me
3138Pyrazol-1-yl4-F—C6H4Me
3139Pyrazol-1-yl4-Cl—C6H4Me
3140Pyrazol-1-yl4-Me—C6H4Me
|
[0712] The following Test Examples illustrate the effects of the fungicide of the present invention. (I. Controlling effects on various plant diseases by foliage application (pot experiment))
Experimental Method
[0713] A test compound was dissolved in a small amount of N,N-dimethylformamide, and the solution was diluted to a given concentration with distilled water containing a spreader. Thus, a liquid sample to be tested was prepared. The liquid sample was sprayed to test plants, and 24 hours thereafter, pathogens were inoculated by the method described below.
[0714] The percent control was calculated according to the following equation:
Percent control (%)=100×severity, number of lesions, etc. in untreated plot−severity, number of lesions, etc. in treated plot/severity, number of lesions, etc. in untreated plot
Test Example 1
[0715] Controlling Effect on Pyricularia oryzae
[0716] Two-week rice seedlings (cv.: AICHIASAHI) were transplanted in plastic cups (each 9 cm in diameter) and cultivated further 2 weeks. The test compound in the form of a solution or a suspension was sprayed to the foliage of the rice seedlings, to which a conidia suspension of Pyricularia oryzae cultured in an oatmeal medium was inoculated by spraying. After the inoculation, the test plant was kept in a moist chamber (28° C., 100% R.H.) for 24 hours, followed by cultivation in a greenhouse for 5 days. Six days after the inoculation, the number of lesions on the leaves of the inoculated plant was measured to calculate the percent control.
[0717] The results are as follows.
5|
|
Controlling effect on Pyricularia
orvzae by foliage application at 500
Compound No.ppm (percent control)
|
190
597
690
797
1390
1590
1690
3970
4090
6197
8197
105A97
106A97
107A90
112A97
113A97
114A90
118B70
122A97
131A90
132A70
136A90
136B70
141A70
141B70
146A97
20190
20590
20690
20790
21570
22170
22570
22670
24170
26170
26690
26790
28170
28790
29590
30070
30570
30670
31270
31390
31490
32290
33670
43670
512A90
512B97
536B70
541B70
605A90
607A90
612A90
613A70
614B70
636A97
636B70
641A70
690A97
70570
70670
71290
71397
71670
72290
73170
73270
74170
80170
81270
91270
936A97
111297
123697
131070
132890
146090
146170
1554A70
158170
158470
167470
2799100
283990
304190
Reference
Fthalide97
|
Test Example 2
[0718] Controlling Effect on Sphaerotheca fuliginea
[0719] Seeds of cucumber (cv.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The liquid test sample in the form of a solution or suspension was sprayed on the surface of their first leaves. The pathogen was inoculated to the leaves by spraying a conidia suspension of Sphaerotheca fuliginea which had been cultured on the cucumber leaves. After the inoculation, the plants were kept in a greenhouse at 20° C. for 10 days. Then, the infected area on the leaf was observed, and the percent control was calculated.
[0720] The results are as follows.
6|
|
Controlling effect on Sphaerotheca
fuliginea by foliage application at
Compound No.500 ppm (percent control)
|
1100
5100
7100
13100
15100
16100
39100
40100
57 90
101A 70
104A 97
105A100
106A100
106B 97
107A100
112A100
112B 90
113A100
113B 90
114A100
119A 97
122A100
122B100
130A100
131A100
131B100
132A100
136A100
136B100
141A100
141B100
144A100
144B 70
146A 97
161100
201100
205100
206100
207100
215100
221 97
226 70
227 97
261 97
266 97
267100
270 97
275100
278 97
294 97
300 70
305100
306 97
312100
313100
314100
322100
336100
412100
436100
512A100
512B100
536A 90
536B100
541A100
541B100
605A100
605B100
606A100
606B 90
607A 97
607B 97
612A100
612B100
613A100
613B 97
614B 97
636A100
636B100
641A100
641B100
690A100
690B100
701 97
705100
706100
707100
712100
713100
716100
722100
731100
732100
736100
741100
801100
805 97
807100
812100
836A100
836B100
844 97
905 90
912100
936A100
936B 97
1112100
1114 70
1121100
1122B100
1123 97
1136100
1161 70
1236100
1304 70
1310 90
1311 70
1312 70
1328100
1341A 70
1341B 70
1428100
1478 70
1514 97
1515 70
1581 70
1854100
1590 70
1634A100
1634B 70
1674 70
1721100
1734 90
1735100
1826 70
2001 70
2012100
2014100
2036100
2044 97
2120 70
2507100
2528100
2799100
2839100
3041 97
Reference
Fenarimol 97
|
Test Example 3
[0721] Controlling Effect on Botrytis cinerea
[0722] The seeds of cucumber (cv.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the surface of their first leaves, and mycelial disks (4 mm φ) of Botrytis cinerea cultured on the potato sucrose agar medium were put on the leaf surfaces to inoculate the cucumber seedlings with the pathogen. The plants were kept in a moist chamber at 20° C. for 3 days. The diameter of the lesions on the leaves was measured and the percent control was calculated.
[0723] The results are as follows.
7|
|
Controlling effect on Botrytis cinerea
by foliage application at 500 ppm
Compound No.(percent control)
|
1100
5 70
6100
7100
13 70
15100
40 70
61100
81 90
106A 70
122A 70
130A 70
132A 70
141A 90
144A 70
201 70
205 70
206 97
207100
215 97
314 70
605A 70
607A 70
713 70
732 70
741 90
Reference
Fenarimol 97
|
Test Example 4
[0724] Controlling Effect on Erysiphe araminis f. sp. tritici
[0725] The seeds of wheat (cv.: NOR1 N No. 61) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the seedlings, and conidia of Erysiphe graminis f. sp. tritici cultured on wheat leaves were dropped on the test plants to inoculate the plants with the pathogen. After the inoculation, the plants were kept in a greenhouse at 20° C. for 10 days. The infected area on the leaf was observed, and the percent control was calculated.
[0726] The results are as follows.
8|
|
Controlling effect on Erysiphe
graminis f. sp. tritici by foliage
application at 500 ppm
Compound No.(percent control)
|
190
590
6100
7100
1390
1597
1690
4097
5770
6197
8197
104A90
104B70
105A70
106A70
107A70
112A100
113A90
114A90
122A97
131A90
132A70
136A90
136B70
141A90
16170
20190
20690
207100
21590
22170
22670
22770
23590
26197
26570
26697
26797
27090
27590
27890
28190
29590
30590
30670
312100
31370
31470
32270
33697
41270
43690
512A97
512B97
536A97
536B100
541A90
541B90
605A90
605B90
606A70
607A90
607B70
612A100
612B100
613A90
613B70
614B70
636A100
636B100
641A90
641B90
690A100
690B100
70170
70690
70790
712100
71390
71670
72290
73170
73270
736100
74190
80190
812100
836A97
836B97
91290
936A97
936B90
110190
111290
111470
112190
1122A70
1122B90
112390
113690
116190
123690
131090
131170
132890
1341A90
1341B90
142870
145570
146090
147890
151470
151590
1554A70
1554B70
1584100
1634A97
165470
166570
166770
167470
172190
173470
173597
182990
201270
203690
279997
283997
Reference
Fenarimol97
|
Test Example 5
[0727] Controlling Effect on Puccinia coronata
[0728] The seeds of oat (cv.: PC-38) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the seedlings. Spores of Puccinia coronata cultured on oat leaves were collected, diluted about 10-fold with talc, and sprayed to the test plants to inoculate the plants with the pathogen. After the inoculation, the plants were kept in a moist chamber at 20° C. for 1 day and then in a greenhouse at 20° C. for 8 days. The infected area on the leaf was observed, and the percent control was calculated.
[0729] The results are as follows.
9|
|
Controlling effect on Puccinia
coronata by foliage application
Compound No.at 500 ppm (percent control)
|
197
590
6100
797
1397
15100
16100
4070
5790
6197
8197
112A100
136A100
136B97
16197
20190
20570
20697
20797
21590
26790
27590
27890
29870
31297
336100
43690
536A90
536B97
612A97
636A100
636B90
70197
712100
72297
736100
80197
91497
936A90
100170
111270
111370
113690
123697
132870
147870
158470
172170
200170
Reference
Fenarimol97
|
Test Example 6
[0730] Controlling Effect on Pseudoperonospora cubensis
[0731] The seeds of cucumber (var.: TSUKUBASHIROIBO) were sown in plastic cups (each 9 cm in diameter), followed by cultivation for 2 to 3 weeks. The test compound in the form of a solution or suspension was sprayed to the surface of their first leaves, and a zoosporangia suspension of Pseudoperonospora cubensis cultured on cucumber leaves was dropped on the above leaf surfaces to inoculate the test plants with the pathogen. After the inoculation, the plants were kept in a moist chamber at 20° C. for 10 days. Then, the area of the lesions around the inoculum were observed and the percent control was calculated.
[0732] The results are as follows.
10|
|
Controlling effect on
Pseudoperonospora cubensis by foliage
application at 500 ppm
Compound No.(percent control)
|
105A100
106A100
106B100
112A 97
113A100
119A 85
122A100
130A100
131A100
132A100
141A100
144A100
146A100
305100
306100
313100
314100
412100
512A100
512B100
536B100
541A100
541B100
605A100
606A 95
606B100
607A 97
607B 97
612A100
612B100
613A 70
613B100
614B100
641A100
690A100
690B100
701100
705100
706100
713100
716100
722100
731100
732100
741100
801100
844100
905 99
1721100
2014100
2044100
2507100
2528100
2799 95
2839 95
Reference
Benalaxyl 97
|
[0733] As described above, the present invention provides a novel oxime derivative, particularly a heterocyclic compound substituted with α-(O-substituted oxyimino)-2-substituted benzyl, having potent fungicidal activity, a process for producing it, intermediates therefor, and a fungicide containing it as an active ingredient.
Claims
- 1. A compound of the formula (I):
- 2. A compound according to claim 1, wherein the optionally substituted heterocyclic group represented by R1 is pyridyl, pyrimidinyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, pyridazinyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, oxazolyl, thiazolyl, oxadiazolyl, triazolyl, quinolyl, indolyl, benzisothiazolyl, benzisoxazolyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof.
- 3. A compound according to claim 1, wherein R1 is phenyl or a heterocyclic group, each of which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, lower alkyl, halogenated lower alkyl, lower alkoxy, lower alkylthio, phenyl, phenoxy and nitro, or a salt thereof.
- 4. A compound according to claim 1, wherein R1 is phenyl; phenyl substituted with halogen and/or lower alkyl; or pyridyl substituted with halogen and/or halogenated lower alkyl; or a salt thereof.
- 5. A compound according to claim 1, wherein R1 is phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 4-chloro-2-methylphenyl, 2-chloropyridin-3-yl, 3,5-dichloropyridin-2-yl, 5-trifluoromethylpyridin-2-yl, 5-trifluoromethyl-3-chloropyridin-2-yl or 3-trifluoromethyl-5-chloropyridin-2-yl, or a salt thereof.
- 6. A compound according to claim 1, wherein R1 is a group of the formula (a):
- 7. A compound according to claim 1, wherein R9 and R10 are the same or different and are hydrogen, alkyl, haloalkyl, alkoxyalkyl, alkylcarbonyl, optionally substituted phenyl, optionally substituted naphthyl or an optionally substituted heterocyclic group, or R9 and R10 are linked together to form a cyclopentane or cyclohexane ring which may form a condensed ring with another ring, or a salt thereof.
- 8. A compound according to claim 1, wherein R9 is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of halogen, optionally substituted alkyl, optionally substituted hydroxyl, alkylthio, optionally substituted amino, nitro, phenyl and cyano, or a salt thereof.
- 9. A compound according to claim 1, wherein R9 is phenyl which is unsubstituted or substituted with 1 to 3 substituents selected from the group consisting of chlorine, methyl, trifluoromethyl and methoxy, or a salt thereof.
- 10. A compound according to claim 1, wherein R9 is morpholino, pyridyl, pyridazinyl, pyrazolyl, pyrimidinyl, furyl, thienyl, oxazolyl, isoxazolyl, benzothiazolyl, quinolyl, quinazolinyl or pyrazinyl, each of which is unsubstituted or substituted, or a salt thereof.
- 11. A compound according to claim 1, wherein R10 is hydrogen or alkyl, or a salt thereof.
- 12. A compound according to claim 1, wherein R10 is hydrogen, methyl or ethyl, or a salt thereof.
- 13. A compound according to claim 1, wherein R2 is alkyl or alkenyl, or a salt thereof.
- 14. A compound according to claim 1, wherein R2 is methyl, ethyl or allyl, or a salt thereof.
- 15. A compound according to claim 1, wherein R3 is isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, furyl, thienyl, imidazolyl, triazolyl, tetrazolyl, oxadiazolyl, thiazolinyl, isoxazolinyl, imidazolinyl, oxazolinyl or thiazolidinyl, each of which is unsubstituted or substituted, or a salt thereof.
- 16. A compound according to claim 1, wherein R3 is imidazolyl; imidazolyl substituted with lower alkyl; imidazolinyl; triazolyl; imidazolinyl substituted with lower alkyl; isoxazolyl; isoxazolyl substituted with lower alkyl; oxadiazolyl; oxadiazolyl substituted with lower alkyl; isoxazolinyl; isoxazolinyl substituted with lower alkyl; oxazolinyl; pyrazolyl; pyrazolyl substituted with lower alkyl; thiazolinyl; furyl; tetrazolyl substituted with lower alkyl; oxazolyl; isothiazolyl substituted with lower alkyl; thiazolidinyl; or thiazolidinyl substituted with lower alkyl; or a salt thereof.
- 17. A compound according to claim 1, wherein R3 is imidazol-1-yl, imidazol-2-yl, 1-methylimidazol-2-yl, 2-methylimidazol-1-yl, 4-methylimidazol-1-yl, 5-methylimidazol-1-yl, 2-imidazolin-2-yl, 1H-1,2,4-triazol-1-yl, 1-methyl-2-imidazolin-2-yl, isoxazol-3-yl, 3-methylisoxazol-5-yl, 5-methylisoxazol-3-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-ethyl-1,2,4-oxadiazol-5-yl, 2-isoxazolin-3-yl, 2-oxazolin-2-yl, 3-methyl-2-isoxazolin-5-yl, pyrazol-1-yl, 1-methylpyrazol-5-yl, 2-thiazolin-2-yl, 2-furyl, 3-methylisothiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 2-methyltetrazol-5-yl, oxazol-5-yl, isoxazol-5-yl, thiazolidin-2-yl or 3-methylthiazolidin-2-yl, or a salt thereof.
- 18. A compound according to claim 1, wherein R4 is hydrogen, or a salt thereof.
- 19. A compound according to claim 1, wherein M is an oxygen atom, or a salt thereof.
- 20. A compound according to claim 19, wherein R1 is phenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 1);
R1 is 4-chlorophenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 7); R1 is 2-methylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 13); R1 is 4-methylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 15); R1 is 2-ethylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 16); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 39); R1 is phenyl, R2 is ethyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 61); R1 is phenyl, R2 is allyl, R3 is imidazol-1-yl, R4 is hydrogen, and n is 1 (Compound No. 81); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 1-methylimidazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 136); R1 is 4-chloro-2-methylphenyl, R2 is methyl, R3 is 1-methylimidazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 141); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 336); R1 is 5-trifluoromethylpyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 387); R1 is 5-trifluoromethyl-3-chloropyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 390); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 5-methylisoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 436); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 3-methylisoxazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 636); R1 is 5-trifluoromethyl-3-chloropyridin-2-yl, R2 is methyl, R3 is 3-methylisoxazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 690); R1 is 2-methylphenyl, R2 is methyl, R3 is 1,3,4-oxadiazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 712); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 1,3,4-oxadiazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 736); R1 is 4-chloro-2-methylphenyl, R2 is methyl, R3 is 1,3,4-oxadiazol-2-yl, R4 is hydrogen, and n is 1 (Compound No. 741); R1 is 4-chlorophenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 807); R1 is 2-methylphenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 812); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 836); R1 is 2-methylphenyl, R2 is methyl, R3 is 5-methyl-1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 912); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 5-methyl-1,2,4-oxadiazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 936); R1 is 2,5-dimethyl phenyl, R2 is methyl, R3 is 5 -methyl-2-imidazolin-2-yl, R4 is hydrogen, and n is 1 (Compound No. 1136); R1 is 4-chlorophenyl, R2 is methyl, R3 is 1,2,4-oxadiazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 1584); R1 is 2,5-dimethylphenyl, R2 is methyl, R3 is 2-methyl-2H-tetrazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 2036); R1 is 3,5-dichloropyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2276); R1 is 5-chloro-3-trifluoromethylpyridin-2-yl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2306); R1 is a group represented by the formula (a), R9 is 4-chlorophenyl, R10 is methyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2387); R1 is a group of by the formula (a), R9 is 3-trifluoromethylphenyl, R10 is methyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2399); R1 is a group of the formula (a), R9 is 3,4-dichlorophenyl, R10 is methyl, R2 is methyl, R3 is isoxazol-3-yl, R4 is hydrogen, and n is 1 (Compound No. 2408); R1 is a group represented by the formula (a), R9 is 4-chlorophenyl, R10 is methyl, R2 is methyl, R3 is 3-methylisoxazol-5-yl, R4 is hydrogen, and n is 1 (Compound No. 2507); R1 is a group of the formula (a), R9 is 3-trifluoromethylphenyl, R10 is methyl, R2 is methyl, R3 is thiazolidin-2-yl, R4 is hydrogen, and n is 1 (Compound No. 2799); or R1 is a group of the formula (a), R9 is 3-trifluoromethylphenyl, R10 is methyl, R2 is methyl, R3 is 3-methylthiazolidin-2-yl, R4 is hydrogen, and n is 1 (Compound No. 2839).
- 21. A fungicidal composition comprising a compound according to any one of claims 1 to 20 or a salt thereof as an active ingredient.
- 22. A process for producing a compound of the formula (I):
- 23. A process according to claim 22, wherein R3 is pyrrolyl, imidazolyl, pyrazolyl or triazolyl, each of which is unsubstituted or substituted.
- 24. A compound of the formula (V):
- 25. A compound according to claim 24, wherein M is an oxygen atom, or a salt thereof.
- 26. A compound of the formula (XIV):
- 27. A compound according to claim 26, wherein M is an oxygen atom, or a salt thereof.
- 28. A compound of the formula (XLVIII):
- 29. A method for controlling or preventing phytopathogenic fungi which comprises applying as an active ingredient a compound according to claim 1 to a locus where phytopathogenic fungi propagate or will propagate.
- 30. Use of a compound according to claim 1 in the manufacture of a fungicidal composition.
Priority Claims (1)
Number |
Date |
Country |
Kind |
087819/1994 |
Apr 1994 |
JP |
|
Divisions (2)
|
Number |
Date |
Country |
Parent |
09370255 |
Aug 1999 |
US |
Child |
09728321 |
Dec 2000 |
US |
Parent |
08693224 |
Aug 1996 |
US |
Child |
09370255 |
Aug 1999 |
US |