CN1074443A - The heterocyclic fungicides of bridging - Google Patents
The heterocyclic fungicides of bridging Download PDFInfo
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- CN1074443A CN1074443A CN 93100432 CN93100432A CN1074443A CN 1074443 A CN1074443 A CN 1074443A CN 93100432 CN93100432 CN 93100432 CN 93100432 A CN93100432 A CN 93100432A CN 1074443 A CN1074443 A CN 1074443A
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- 0 CC(COC1)C(*)C1=O Chemical compound CC(COC1)C(*)C1=O 0.000 description 1
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
- A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
- A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses the Fungicidal compounds of formula I.
Description
Disclosed invention relates to mycocidal compound and compositions field.
F.Kr
Hnke(Synthesis 1976,1,1-24) disclose the synthetic of following compound,
Do not disclose this compound agrohorticultural bactericide is arranged.
United States Patent (USP) 4,189 323(Hoechst) discloses the light trigger of following compound as free radical reaction or acid catalyzed reaction.
Haginiwa etc. (pharmaceutical journal, 1975,95,204-210) the synthetic of following compound disclosed.
The present invention relates to comprise the formula I compound of all geometrical isomers and steric isomer, and contain these compounds or its agriculture suitable salt or agricultural composition of metal complex,
In the formula:
X is N or CR
4;
Y is N or CR
5;
Z is N or CR
6;
Q is condensed benzene, naphthalene, thiophene, furans, pyrroles, pyridine or a pyrimidine ring, and they randomly are R separately
7And R
8Replace;
A is an abutment-G
1-G
2-G
3-G
4-, G wherein
1, G
2, G
3Or G
4Be O, S(O independently) p, NR
9, CR
10R
11, C(=O), direct key, perhaps a G
1-G
2, G
2-G
3Or G
3-G
4Can form together-CH=CH-; Make G
1, G
2, G
3And G
4In at least one be not direct key;
R
1, R
2, R
3And R
4Be H, halogen, cyano group, hydroxyl, C independently of one another
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, randomly use 1-2 methyl substituted C
3-C
6Cycloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
4Alkenyl, C
2-C
4Halogenated alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, NR
12R
13, randomly use R
14The phenyl or the phenoxy group that replace; Perhaps R
1And R
4, R
2And R
4Or R
2And R
5Can form together-(CH
2)
3-,-(CH
2)
4Or condensed phenyl ring;
R
5And R
6Be H, halogen, C independently of one another
1-C
2Alkyl or C
1-C
2Alkoxyl group;
R
7Be halogen, cyano group, nitro, hydroxyl, hydroxycarbonyl group, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, (C
1-C
4Alkyl)
3Silyl, C
3-C
6Cycloalkyl, C
2-C
5Alkyl-carbonyl, C
2-C
4Alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
5Alkoxy carbonyl, C
2-C
4Alkoxyalkoxy group, NR
15R
16, C(=O) NR
17R
18; Or phenyl, phenoxy group or thiophenyl, they randomly use R separately
19Replace;
R
8And R
14Be 1-2 halogen, 1-2C independently of one another
1-C
3Alkyl, C
1-C
2Halogen alkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
R
9, R
10And R
11Be H or C independently of one another
1-C
2Alkyl;
R
12, R
13, R
15, R
16, R
17And R
18Be H or C independently of one another
1-C
2Alkyl; Perhaps R
12And R
13, R
15And R
16Or R
17And R
18Can form piperidino-(1-position only), pyrrolidyl or morpholino ring with that nitrogen that they connect;
R
19Be halogen, C
1-C
2Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
P is 0,1 or 2;
Condition is:
ⅰ) work as G
1, G
2, G
3Or G
4In any one when being O, they not with O or S(O) the direct Cheng Jian of p;
ⅱ) work as G
1, G
2, G
3Or G
4In any one is S(O) or S(O)
2The time, they not with C(=O) direct Cheng Jian;
ⅲ) in containing the ring of A, heteroatomic overall number is no more than 2;
ⅳ) when X, Y and Z be that CH, A are CH
2, Q is the unsubstituted benzene of condensed, R
1And R
2When being H, R
3It or not unsubstituted phenyl; And
ⅴ) these compounds are not 2-[4,6-two (trichloromethyl)-1,3,5-triazines-2-yl]-1,10-phenanthroline or 2-(2-pyridyl)-1, the 10-phenanthroline.
The invention still further relates to the method for control fungal diseases of plants, comprise the position that to protect with salt that is suitable on the formula IA compound of effective quantity or their agricultural or metal complex processing.
In formula IA:
X is N or CR
4;
Y is N or CR
5;
Z is N or CR
6;
Q is condensed benzene, naphthalene, thiophene, furans, pyrroles, pyridine or a pyrimidine ring, and they can randomly use R separately
7And R
8Replace;
A is an abutment-G
1-G
2-G
3-G
4-, G wherein
1, G
2, G
3Or G
4Be O, S(O independently of one another) p, NR
9, CR
10R
11, C(=O), a direct key, or G
1-G
2, G
2-G
3Or G
3-G
4Can constitute together-CH=CH-; Make G
1, G
2, G
3And G
4In at least one is not direct key;
R
1, R
2, R
3And R
4Be H, halogen, cyano group, hydroxyl, C independently of one another
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, randomly use 1-2 methyl substituted C
3-C
6Cycloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
4Alkenyl, C
2-C
4Halogenated alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, NR
13R
13, randomly use R
14The phenyl or the phenoxy group that replace, or R
1And R
4, R
2And R
4Or R
2And R
5Can form together-(CH
2)
3-,-(CH
2)
4-or a condensed phenyl ring;
R
5And R
6Be H, halogen, C independently of one another
1-C
2Alkyl or C
1-C
2Alkoxyl group;
R
7Be halogen, cyano group, nitro, hydroxyl, hydroxycarbonyl group, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, (C
1-C
4Alkyl)
3Silyl, C
3-C
6Cycloalkyl, C
2-C
5Alkyl-carbonyl, C
2-C
4Alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
5Alkoxy carbonyl, C
2-C
4Alkoxyalkoxy group, NR
15R
16, C(=O) NR
17R
18; Or randomly be R separately
19The phenyl, phenoxy group or the thiophenyl that replace;
R
8And R
14Be 1-2 halogen, 1-2C independently
1-C
3Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
R
9, R
10And R
11Be H or C independently
1-C
2Alkyl;
R
12, R
13, R
15, R
16, R
17And R
18Be H or C independently
1-C
2Alkyl; Perhaps R
12And R
13, R
15And R
16Or R
17And R
18Can form a piperidino-(1-position only) with that nitrogen-atoms that they connected, pyrrolidyl or morpholino ring;
R
19Be halogen, C
1-C
2Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
P is 0,1 or 2;
Condition is:
ⅰ) work as G
1, G
2, G
3Or G
4In any one when being O, they not with O or S(O) the p Direct Bonding;
ⅱ) work as G
1, G
2, G
3Or G
4In any one be S(O) or S(O)
2The time, they not with C(=O) Direct Bonding; With
ⅲ) in containing the ring of A, heteroatomic sum is no more than 2.
In above narration, no matter " alkyl " speech is to use separately or in such as " alkyl sulfenyl " or compound words such as " haloalkyls ", all be meant the straight or branched alkyl; For example, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, sec-butyl, the tertiary butyl, n-pentyl or n-hexyl.
" alkenyl " is meant the alkene of straight or branched; For example, vinyl, 1-propenyl, 2-propenyl, 3-propenyl and different butenyl isomer.
" alkenyloxy " is meant the alkene oxygen base section of straight or branched.The example of alkene oxygen base comprises H
2C=CHCH
2O-, (CH
3) CH=CHCH
2O-, CH
2=CH(CH
3) CH
2O-and CH
2=CHCH
2CH
2O-.
" alkynyl " comprises the alkynes of straight or branched; For example, ethynyl, 1-proyl, 3-proyl and various butynyl isomer.
" alkynyloxy group " is meant the alkynyloxy group part of straight or branched.Example comprises
HC ≡ CCH
2O-and CH
3C ≡ CCH
2O-.
" alkyl sulfenyl " comprises methylthio group, ethylmercapto group and various rosickyite base and butylthio isomer.
" alkyl silyl " comprises (CH
3)
2(t-C
4H
9) Si, (CH
3)
3Si and (CH
3CH
2)
3Si.
The example of " alkyl sulphinyl " comprises CH
3S(O), CH
3CH
2S(O), CH
3CH
2CH
2S(O), (CH
3)
2CHS(O) and CH
3CH
2CH
2CH
2S(O).
The example of " alkyl sulphonyl " comprises CH
3S(O)
2, CH
3CH
2S(O)
2, CH
3CH
2CH
2S(O)
2, (CH
3)
2CHS(O)
2With various butyl alkylsulfonyl isomer.
" alkoxyl group " comprises methoxyl group, oxyethyl group, positive propoxy, isopropoxy and various butoxy isomer.
" cycloalkyl " comprises cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
No matter " halogen " speech is to use separately or use in such as compound words such as " haloalkyls ", and it comprises fluorine, chlorine, bromine or iodine.In addition, when using in such as compound words such as " haloalkyls ", this alkyl can partly or entirely be replaced by halogen atom, and these halogen atoms can be identical or different.The example of " haloalkyl " comprises CF
3, CH
2CL, CH
2CF
3And CF
2CF
3The example of " halogenated alkoxy " comprises CF
3O-, Cl
3CCH
2O-, CF
2HCH
2CH
2O-and CF
3CH
2O-.
The total number of carbon atoms in the substituting group indicates that with prefix " Ci-Cj " wherein i and j are from 1 to 6 numerals.C for example
1-C
3Alkyl sulphonyl is represented from methyl sulphonyl to the sulfonyl propyl base; C
2Alkoxyalkoxy group is represented CH
3OCH
2O; C
3Alkoxyalkoxy group typical example such as CH
3OCH
2CH
2O; C
4The total that the alkoxyalkoxy group representative replaces with second alkoxyl group contains the various isomer of the alkoxyl group of 4 carbon atoms, and the example comprises CH
3CH
2CH
2OCH
2O and CH
3CH
2OCH
2CH
2O.The example of " alkoxyalkyl " comprises CH
3OCH
2, CH
3OCH
2CH
2And CH
3CH
2OCH
2C
2Alkyl-carbonyl is represented C(=O) CH
3, C
4Alkyl-carbonyl is represented C(=O) CH
2CH
2CH
3And C(=O) CH(CH
3)
2The example of " alkoxy carbonyl " comprises CO
2CH
3, CO
2CH
2CH
3, CO
2CH
2CH
2CH
3, CO
2CH(CH
3)
2With various butoxy carbonyl isomer.
The salt of The compounds of this invention comprises the acid salt that forms with mineral acid or organic acid.These sour examples comprise hydrochloric acid, nitric acid, sulfuric acid, acetate, oxalic acid or 4-toluenesulphonic acids.When The compounds of this invention contains acidic-group, for example when carboxylic acid group, phenolic group or sulfydryl, the salt of The compounds of this invention also comprises those salt that form with organic or inorganic alkali.
The metal complex of The compounds of this invention comprises and metal-salt, for example copper, zinc, manganese and molysite, the complex compound of formation.These complex compounds can prepare before the preparation compound, also can prepare by proper metal salt is added in the prescription.
With regard to maximum fungicidal activity and/or with regard to being easy to synthesize, preferred formula I compound is:
1. the salt or the metal complex that are suitable on following formula I compound or their agricultural, wherein,
X is N or CR
4;
Y is N or CR
5;
Z is N or CR
6;
Q is condensed benzene, naphthalene, thiophene, furans, pyrroles, pyridine or a pyrimidine ring, and they randomly use R separately
7And R
8Replace;
A is the abutment that is selected from following radicals:
-CR
10R
11-;-G-;-（CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11）-;-（CH＝CH）-;-[O-C（＝O）]-;
-[NR
9-C（＝O）]-;-（CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11）-;-（CR
10R
11-G-CR
10R
11）-;
-（CR
10R
11-CH＝CH）-;-（O-CR
10R
11-O）-;
-[O-C（＝O）-CR
10R
11]-;-[CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）]-;-[C（＝O）-CH＝CH]-;
-[O-C（＝O）-O]-;-[NR
9-C（＝O）-NR
9]-;
-（CR
10R
11-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-CR
10R
11-CH＝CH）-;
-（CR
10R
11-CH＝CH-CR
10R
11）-;-（CH＝CH-CH＝CH）-;
-（O-CR
10R
11-O-CR
10R
11）-;
-（O-CR
10R
11-CR
10R
11-O）-;
-[O-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-CR
10R
11-NR
9-C（＝O）]-;
So A forms a 5-8 unit ring with the atom that is connected; The directivity of A can be that the left side and the Q ring key of A closes, and the right and pyridyl ring (are worked as Z=CR
8) or pyrimidine-ring (when Z=N) bonding, or the left side of A and pyridyl ring or pyrimidine-ring bonding, the right and Q bonding;
G is O, S(O) p, NR
9Or C(=O);
R
1, R
2, R
3And R
4Be H, halogen, cyano group, hydroxyl, C independently of one another
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, randomly use 1-2 methyl substituted C
3-C
6Cycloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
4Alkenyl, C
2-C
4Halogenated alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, NR
12R
13, randomly use R
14The phenyl or phenoxy group or the R that replace
1And R
4, R
2And R
4Or R
2And R
5Can form together-(CH
2)
3-,-(CH
2)
4-or a condensed phenyl ring;
R
5And R
6Be H, halogen, C independently
1-C
2Alkyl or C
1-C
2Alkoxyl group;
R
7Be halogen, cyano group, nitro, hydroxyl, hydroxycarbonyl group, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, (C
1-C
4Alkyl)
3Silyl, C
3-C
6Cycloalkyl, C
2-C
5Alkyl-carbonyl, C
2-C
4Alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
5Alkoxy carbonyl, C
2-C
4Alkoxyalkoxy group, NR
15R
16, C(=O) NR
17R
18; Or phenyl, phenoxy group or thiophenyl, their available independently of one another R
19Replace;
R
8And R
14Be 1-2 halogen, 1-2C independently of one another
1-C
3Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
R
9, R
10And R
11Be H or C independently of one another
1-C
2Alkyl;
R
12, R
13, R
15, R
16, R
17And R
18Be H or C independently
1-C
2Alkyl; Perhaps R
12And R
13, R
15And R
16Or R
17And R
18Can form a piperidino-(1-position only) with that nitrogen-atoms that they connected, pyrrolidyl or morpholino ring;
R
19Be halogen, C
1-C
2Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
P is 0,1 or 2.
2. preferred 1 compound, wherein:
X is CR
4;
Y is N or CH;
Z is N or CH; With
A is an abutment that is selected from following group:
-（CR
10R
11-CR
10R
11）-;-（G-CR
10R
11）-;
-（CH＝CH）-;-[O-C（＝O）]-;-[NR
9-C（＝O）]-;
-（CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11）-;-（CR
10R
11-G-CR
10R
11）-;
-（CR
10R
11-CH＝CH）-;-（O-CR
10R
11-O）-;
-[O-C（＝O）-CR
10R
11]-;-[CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）]-;-[C（＝O）-CH＝CH]-;
-[O-C(=O)-O]-; With-[NR
9-C(=O)-NR
9]-.
3. preferred 2 compound, wherein:
Q is condensed benzene, thiophene, furans or a pyridine ring, and they respectively can be from randomly using R
7And R
8Replace;
A is selected from following group:
-（CH
2-CH
2）-;-[CH
2-C（＝O）]-;-（CH＝CH）-;
-[C（＝O）-O]-;-[C（＝O）-NR
9]-;-（CH
2-CH
2-CH
2）-;
-（O-CH
2-O）-;-（CH
2-CH
2-O）-;
-[CH
2-CH
2-S（O）
P]-;-（CH
2-CH
2-NR
9）-;
-（CH
2-O-CH
2）-;-[CH
2-S（O）
P-CH
2]-;
-（CH
2-NR
9-CH
2）-;-[O-C（＝O）-O]-;
R
1, R
2, R
3And R
4Be hydrogen, halogen, C independently
1-C
4Alkyl, C
1-C
4Haloalkyl, cyclopropyl, C
1-C
4Alkoxyl group or C
2-C
3Alkynyl; With
R
7Be halogen, cyano group, C
1-C
4Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy or C
2-C
4Alkoxyalkoxy group.
4. preferred 3 compound, wherein:
Q is randomly available R
7And R
8The fused benzene rings that replaces;
A is selected from following group:
-（CH
2-CH
2）-;-（CH＝CH）-;-[C（＝O）-O]-;
-[C（＝O）-NR
9]-;-（CH
2-CH
2-CH
2）-;-（O-CH
2-O）-;
-（CH
2-CH
2-O）-;-[CH
2-CH
2-S（O）
P]-;
-（CH
2-CH
2-NR
9）-;-（CH
2-O-CH
2）-;
-[CH
2-S(O)
P-CH
2]-and-(CH
2-NR
9-CH
2)-.
With regard to maximum fungicidal activity and/or with regard to being easy to synthesize, particularly preferably be 6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine.
With regard to maximum fungicidal activity and/or with regard to being easy to synthesize, preferable methods is:
1. method of preventing and treating fungal diseases of plants, it comprises with salt that is suitable on the formula IA compound of effective quantity or their agricultural or metal complex handles the position that will protect, wherein:
X is N or CR
4;
Y is N or CR
5;
Z is N or CR
6;
Q is condensed benzene, naphthalene, thiophene, furans, pyrroles, pyridine or pyrimidine ring, their randomly available separately R
7And R
8Replace;
A is the abutment that is selected from following group :-CR
10R
11-;-G-;
-（CR
10R
11-CR
10R
11）-;-（G-CR
10R
11）-;
-（CH＝CH）-;-[O-C（＝O）]-;-[NR
9-C（＝O）]-;
-（CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11）-;-（CR
10R
11-CH＝CH）-;
-（O-CR
10R
11-O）-;-[O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）]-;-[C（＝O）-CH＝CH]-;
-[O-C（＝O）-O]-;-[NR
9-C（＝O）-NR
9]-;
-（CR
10R
11-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-CR
10R
11-CH＝CH）-;
-（CR
10R
11-CH＝CH-CR
10R
11）-;
-（CH＝CH-CH＝CH）-;-（O-CR
10R
11-O-CR
10R
11）-;
-（O-CR
10R
11-CR
10R
11-O）-;
-[O-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-NR
9-C(=O)-CR
10R
11]-; With
-[CR
10R
11-CR
10R
11-NR
9-C（＝O）]-;
Make A form a 5-8 unit ring with the atom that is connected; The directivity of A can be that its left side and Q ring key close, and the right and pyridyl ring (are worked as Z=CR
6) or pyrimidine-ring (working as Z=N) bonding, or, the left side of A and pyridyl ring or pyrimidine-ring bonding, the right and Q bonding;
G is O, S(O) p, NR
9Or C(=O);
R
1, R
2, R
3And R
4Be H, halogen, cyano group, hydroxyl, C independently of one another
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, randomly use 1-2 methyl substituted C
3-C
6Cycloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
4Alkenyl, C
2-C
4Halogenated alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, NR
12R
13, randomly use R
14The phenyl or phenoxy group or the R that replace
1And R
4, R
2And R
4Or R
2And R
5Can form together-(CH
2)
3-,-(CH
2)
4-or a condensed phenyl ring;
R
5And R
6Be H, halogen, C independently
1-C
2Alkyl or C
1-C
2Alkoxyl group;
R
7Be halogen, cyano group, nitro, hydroxyl, hydroxycarbonyl group, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, (C
1-C
4Alkyl)
3Silyl, C
3-C
6Cycloalkyl, C
2-C
5Alkyl-carbonyl, C
2-C
4Alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
5Alkoxy carbonyl, C
2-C
4Alkoxyalkoxy group, NR
15R
16, C(=O) NR
17R
18; Or randomly use R separately
19The phenyl, phenoxy group or the thiophenyl that replace;
R
8And R
14Be 1-2 halogen, 1-2C independently of one another
1-C
3Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
R
9, R
10And R
11Be H or C independently
1-C
2Alkyl;
R
12, R
13, R
15, R
16, R
17And R
18Be H or C independently of one another
1-C
2Alkyl; Perhaps R
12And R
13, R
15And R
16Or R
17And R
18Can constitute a piperidino-(1-position only) with that N that is connected, pyrrolidyl or morpholino ring;
R
19Be halogen, C
1-C
2Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
P is 0,1 or 2.
2. according to a kind of method of preferable methods 1, wherein:
X is CR
4;
Y is N or CH;
Z is N or CH; With
A is an abutment that is selected from following group :-(CR
10R
11-CR
10R
11)-;
-（G-CR
10R
11）-;-（CH＝CH）-;-[O-C（＝O）]-;
-[NR
9-C（＝O）]-;
-（CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11）-;-（CR
10R
11-CH＝CH）-;
-（O-CR
10R
11-O）-;-[O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）]-;-[C（＝O）-CH＝CH]-;
-[O-C(=O)-O]-; With-[NR
9-C(=O)-NR
9]-.
3. according to a kind of method of preferable methods 2, wherein:
Q is condensed benzene, thiophene, furans or pyridine ring, their randomly available separately R
7And R
8Replace;
A is selected from following group:
-（CH
2-CH
2）-;-[CH
2-C（＝O）]-;-（CH＝CH）-;
-[C（＝O）-O]-;-[C（＝O）-NR
9]-;
-（CH
2-CH
2-CH
2）-;-（O-CH
2-O）-;
-（CH
2-CH
2-O）-;-[CH
2-CH
2-S（O）
P]-;
-（CH
2-CH
2-NR
9）-;-（CH
2-O-CH
2）-;
-[CH
2-S（O）
P-CH
2]-;-（CH
2-NR
9-CH
2）-;
-[O-C（＝O）-O]-;
R
1, R
2, R
3And R
4Be H, halogen, C independently of one another
1-C
4Alkyl, C
1-C
4Haloalkyl, cyclopropyl, C
1-C
4Alkoxyl group or C
2-C
3Alkynyl; With
R
7Be halogen, cyano group, C
1-C
4Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy or C
2-C
4Alkoxyalkoxy group.
4. according to a kind of method of preferable methods 3, wherein:
Q randomly uses R
7And R
8The fused benzene rings that replaces; With
A is selected from following group:
-（CH
2-CH
2）-;-（CH＝CH）-;-[C（＝O）-O]-;
-[C（＝O）-NR
9]-;-（CH
2-CH
2-CH
2）-;
-（O-CH
2-O）-;-（CH
2-CH
2-O）-;
-[CH
2-CH
2-S（O）
P]-;-（CH
2-CH
2-NR
9）-;
-(CH
2-O-CH
2)-;-[CH
2-S(O)
P-CH
2]-and
-（CH
2-NR
9-CH
2）-.
With regard to fungicidal activity and/or with regard to being easy to synthesize, particularly preferably be scheme according to preferred version 4, compound wherein is 6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine.
In the following method one or more, or, can be used for preparing compound of the present invention for conspicuous other modification of this area professional.Except as otherwise noted, substituting group in the following method and previous definition is identical.This area the professional will recognize that, these methods may need to utilize protecting group or functional group's change subsequently, to avoid may bad side reaction taking place responsive substituting group to reaction conditions.One of skill in the art also will appreciate that, formula I compound and intermediate cited below can carry out various electrophilic reactions, nucleophilic reaction, free radical reaction, organometallic reaction, oxidizing reaction and reduction reaction, so that add substituting group or revise existing substituting group.
Y is that N, X are CR in formula I compound
4The time, it can be according to shown in the reaction formula 1, and the amidine of through type II and formula III compound react in the presence of suitable alkali and make.Typically react to relate to amidine II or its conjugation acid salt (for example hydrochloride) are being combined in the presence of the normal alkali from catalytic quantity to 2.5 in the inert solvent with 1 to 1.5 normal formula III compound.Typical alkali comprises alkali metal alcoholates (for example sodium methylate and sodium ethylate) and organic amine alkali (for example triethylamine and triethyl aniline).Typical solvent comprises alcohols (for example methyl alcohol and ethanol), cyclic ethers class (for example tetrahydrofuran (THF) is with diox), pyridine and dimethyl formamide.Temperature of reaction generally is by 50 ℃ of reflux temperatures to employed concrete solvent, and reaction was finished in 1 to 6 hour usually.Work as R
1And R
2When being the substituting group that links to each other through heteroatoms, for example alkoxyl group and halogen can not be used this method.Formula III compound is known in the art, can prepare according to currently known methods.
Reaction formula 1
R wherein
20Be C
1-C
4Alkyl;
Or, when Y is that N, X are CR
4The time, formula I compound can be by shown in the reaction formula 2, and the amidine of through type II and formula IV compound react in the presence of optional a kind of alkali and make.Typically react to relate to amidine II or its conjugation acid salt (for example hydrochloride) are combined in the presence of in 0 to the 2.5 equivalent alkali in the inert solvent with 1 to 1.5 equivalent formula IV compound.Typical alkali comprises alkali metal alcoholates (for example methylate and sodium ethylate) and organic amine alkali (for example triethylamine and Diethyl Aniline).Typical solvent comprises alcohols (for example ethanol of methyl alcohol), cyclic ethers class (for example tetrahydrofuran (THF)), pyridine and dimethyl formamide.Temperature of reaction generally is the reflux temperature from 50 ℃ to used concrete solvent, and reaction was finished in 24 hours usually.Work as R
1And R
2When being the substituting group that links to each other by heteroatoms, for example alkoxyl group and halogen, this method is inapplicable.Formula IV compound is known in the art, can prepare according to method (Hauser et.al., Organic Reaction, 1954,8,59-196).
Reaction formula 2
Perhaps, as shown in reaction formula 3, when Y is that N and X are CR
4The time, amidine that formula I compound can the through type II and formula V compound react in the presence of optional alkali and make L in the formula V compound
1Be hydrogen or suitable leavings group, for example halogen, alkoxyl group, alkyl sulfenyl, dialkyl amido, haloalkyl sulfonyloxy or aryl-sulfonyl oxygen.Amidine or its conjugation acid salt (for example hydrochloride) that typical reaction relates to the formula II combine in the presence of in 0 to the 2.5 equivalent alkali in the inert solvent with 1 to 2.5 normal formula V compound.Work as L
1When being hydrogen, at least will be with 2 normal formula V compounds, because this reagent also plays oxygenant for the dihydro-pyrimidin intermediate.Typical alkali comprises alkali alcoholate (for example sodium methylate and sodium ethylate) and organic amine alkali (for example triethylamine and Diethyl Aniline).Typical solvent comprises alcohol (for example methyl alcohol and ethanol), cyclic ethers (for example tetrahydrofuran (THF) is with diox), pyridine and dimethyl formamide.Temperature of reaction generally is the reflux temperature from 50 ℃ to used concrete solvent, and reaction was finished in 24 hours usually.Work as R
1When being the substituting group that connects through heteroatoms, for example alkoxyl group and halogen, this method is inapplicable.Work as R
2Be to compare L
1Better during leavings group, this method is also inapplicable, because L
1To be retained in the product.Formula V compound is well-known in the art, can prepare according to following method:
Abdulla et al., Tetrahedron, 1979,35,1675-1735; Tominaga et al., Heterocycles, 1989,29,1409-1429; " The Chemistry of Enones ", Patai and Rappoport, Eds., Wiley, 1989.
Reaction formula 3
Or, when Y is that N, X are CR
4, R
2When being H, amidine and formula VI compound that formula I compound can the through type II make by reacting shown in the reaction formula 4.Typical reaction comprises the acid amides of formula II or its conjugation acid salt (for example hydrochloride) and 1 to 3 normal formula VI compound heated under 1 to 6 hour the condition at solubilizing agent not and at 50 to 150 ℃ and combines.Work as R
1When being the substituting group that is connected by heteroatoms, for example alkoxyl group and halogen, this method is inapplicable.
Reaction formula 4
R wherein
20Be C
1-C
4Alkyl
R
1Or R
2The formula I compound that is hydrogen can be according to shown in the reaction formula 5, removes by the reductibility of halogen, alkyl sulfenyl, alkyl sulphinyl or alkyl sulphonyl to make.Reduction for halogen is removed, and is reflected under the hydrogen and carries out in the inert solvent with catalyzer (for example palladium/charcoal).The example of inert solvent has water, alcohol (as methyl alcohol or ethanol), ethyl acetate or toluene, and temperature of reaction is 25 ° to 50 ℃.The dehalogenation effect can be carried out in the presence of the alkali (for example ammonia, ammonium hydroxide, yellow soda ash or sodium acetate) of equivalent, so that with the hydrogen halide neutralization that discharges.
Remove for the reductibility of alkyl sulfenyl, alkyl sulphinyl or alkyl sulphonyl, reaction usually as above do not exist and randomly under hydrogen, react at alkali as catalyzer with Raney nickel.
Reaction formula 5
Work as R
1Or R
2When being alkyl or halogenated alkyl, formula I compound can pass through R
1Or R
2Be that the formula I compound of leavings group (for example halogen, alkyl sulphinyl or alkyl sulphonyl) and the dialkyl malonate of formula VII react in the presence of alkali, then hydrolysis and decarboxylation prepare, as shown in reaction formula 6.First step reaction is to pass through R
1And R
2Be that the formula I compound of leavings group combines in the presence of in 1 to the 4 normal suitable alkali in inert solvent with 1 to 2 normal formula VII compound and carries out.Typical alkali comprises alkalimetal hydride (for example sodium hydride and potassium hydride KH), lithium alkylide (for example butyllithium), alkali metal amide (for example diisopropyl amide lithium) and alkali metal hydroxide (for example sodium hydroxide).Typical solvent comprises nitrile (for example acetonitrile), ethers (for example ether and tetrahydrofuran (THF)), halogenated hydrocarbon (for example chloroform), aromatic hydrocarbons (for example benzene and toluene), ketone (for example acetone) and dimethyl sulfoxide (DMSO).Temperature of reaction is the reflux temperature from 0 ℃ to used concrete solvent normally, and reaction was finished in 0.5 to 24 hour usually.Hydrolysis reaction usually in the water that randomly is added with organic cosolvent (for example methyl alcohol, ethanol, tetrahydrofuran (THF) or diox) in 2 to 4 normal alkali, normally carry out in the presence of alkali metal hydroxide (for example sodium hydroxide) or the alkaline carbonate (as yellow soda ash).Temperature of reaction generally is the reflux temperature from 0 ℃ to the solvent for use mixture, and hydrolysis was finished after 0.2 to 24 hour usually.Hydrolysate (propanedioic acid intermediate) need not to separate, so decarboxylation normally directly is added to 2.5 to 6 normal acid (for example sulfuric acid, hydrochloric acid or acetate) in the hydrolysis reaction mixture and finishes.Then with the mixture of acidifying in room temperature to heating between the reflux temperature of mixture 0.2 to 24 hour so that carry out decarboxylation, obtain R wherein
1Or R
2It is the formula I compound of alkyl or haloalkyl.Formula VII compound is well-known in the art, can prepare according to method.
Reaction formula 6
Wherein:
R
20Be C
1-C
4Alkyl; With
R
21Be C
1-C
5Alkyl or C
1-C
3Haloalkyl.
The compound of formula I is worked as R
1Or R
2Be cyano group, hydroxyl, alkyl sulfenyl, alkoxyl group, halogenated alkoxy, alkenyloxy, alkynyloxy group, dialkyl amido or replacement phenoxy group the time, R that can be by wherein
1Or R
2Be the formula I compound and the nucleophilic L of leavings group (for example halogen, alkyl sulphinyl or alkyl sulphonyl)
2-M
1In the presence of optional alkali, react and prepare, as described in reaction formula 7.The typical R that comprises wherein that reacts
1Or R
2Be the formula I compound and 1 to the 2 normal L of leavings group
2-M
1Compound combines in a kind of inert solvent.Work as M
1When being hydrogen, in reaction, add 1 to 2.2 normal alkali.Typical alkali comprises alkalimetal hydride (for example sodium hydride), basic metal (for example sodium) and lithium alkylide (for example butyllithium).Typical solvent comprises alcohols (for example methyl alcohol and ethanol), ethers (for example ether, tetrahydrofuran (THF) He diox), nitrile (for example acetonitrile), dimethyl formamide and dimethyl sulfoxide (DMSO).The solvent that nucleophilie nucleus ability is arranged, alcohol for example, just they not with nucleophilic L
2-M
1Just can use during competition.Temperature of reaction generally is the reflux temperature from 0 ℃ to used concrete solvent, and reaction was finished in 2 days usually.L
2-M
1Represent common agents, for example sodium alkoxide, alcohol, phenol, sodium cyanide, sodium hydroxide, dialkylamine etc.Can add catalyzer, for example copper, cuprous chloride (I), cupric chloride (II) and cupric oxide (II) react with promotion.
Reaction formula 7
Wherein, L
2Be cyano group, hydroxyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkene oxygen base, C
2-C
4Alkynyloxy group, NR
12R
13, or use R
14The phenoxy group that replaces; M
1Middle hydrogen or basic metal.
The compound of formula I is worked as R
1Or R
2Be alkyl sulphinyl or alkyl sulphonyl, can be according to shown in the reaction formula 8, by R wherein
1Or R
2The formula I compound oxidation that is the alkyl sulfenyl prepares.Typical reaction comprises formula I compound (R
1Or R
2Be the alkyl sulfenyl) mix in the inert solvent with suitable oxygenant.R in want product I
1Or R
2When being alkyl sulphinyl, use 1 to 1.1 normal oxygenant; R in the product I
1Or R
2When being alkyl sulphonyl, using 2 to 2.2 equivalents is oxygenants.Typical oxidizing agents is 3-chloroperoxybenzoic acid, monoperphthalic acid magnesium, peracetic acid, hydrogen peroxide etc.Typical solvent comprises halohydrocarbon (for example methylene dichloride, 1,2-ethylene dichloride and chloroform) and aromatic hydrocarbons (for example toluene).Temperature of reaction generally is the reflux temperature from 0 ℃ to used concrete solvent, and reaction was finished in 24 hours usually.
Reaction formula 8
R wherein
20Be C
1-C
4Alkyl.
Work as R
1Or R
2When being halogen, formula I compound can be used R according to described in the reaction formula 9
1Or R
2Be that the formula I compound of hydroxyl and a kind of halogenating agent react and prepare, the example of halogenating agent comprises phosphorus trichloride, phosphorus pentachloride, phosphorus tribromide, phosphorus pentabromide, Phosphorus Oxychloride, phosphorus oxybromide, thionyl chloride, phosgene etc.Typical reaction comprises R
1And R
2Be that the formula I compound of hydroxyl is with 1.1 to 10 equivalents, preferably 2 to 4 normal excessive halogenating agents mix.This reaction can be carried out in the presence of not at solvent, or carries out in the presence of suitable inert solvent, comprises aromatic hydrocarbons (for example benzene and toluene), halohydrocarbon (for example methylene dichloride and chloroform) and hydrocarbon (for example hexane).Temperature of reaction can be good with 25 ℃ to 100 ℃ from-10 ℃ to 200 ℃.Reaction was generally finished after 1 to 24 hour.
Reaction formula 9
When Y is that N, X are CR
4, R
1When being hydroxyl, formula I compound can be according to shown in the reaction formula 10, and the 'beta '-ketoester of the amidine of through type II and formula VIII reacts in the presence of alkali and prepares.Typical reaction comprise with amidine II or its conjugation acid salt (for example hydrochloride) and 1 to 1.5 normal formula VIII compound in inert solvent in combining in the presence of the normal alkali from catalytic quantity to 1.5.Typical alkali comprises alkali metal hydroxide (for example sodium hydroxide), alkaline carbonate (for example salt of wormwood), amine (for example triethylamine and Diethyl Aniline) and alkali metal alcoholates (for example sodium methylate and sodium ethylate).Typical solvent comprises alcohol (for example methyl alcohol and ethanol), cyclic ethers (for example tetrahydrofuran (THF) is with diox), pyridine, dimethyl formamide and water.Temperature of reaction generally is the reflux temperature from room temperature to used concrete solvent, and reaction was finished in 1 to 24 hour usually.An example of this method by Lafferty etc. propose (J.org.Chem.1967,32,1591-1596).Work as R
2Be (for example alkoxyl group) when connecting by heteroatoms, product often loses R
2, obtain R
2It is the product I of hydroxyl; In the document of above-mentioned Lafferty etc., can also find an example that uses the dialkyl malonate VIII to obtain this reaction of dihydroxy-pyrimidine.In reaction formula 10, also example illustrated method according to people such as Brown (Aust.J.Chem.1982,35,1203-1207), the ester of through type IX and formula X compound prepared in reaction formula I compound, Y wherein is that N, X are CR
4, R
1It is hydroxyl.
Perhaps, can with people's such as Kato method (Chem.Pharm.Bull.1976,24,356-359) be used for the imidoether (its structure is seen reaction formula 11) of formula XII, to prepare same compound.
Reaction formula 10
R wherein
20Be C
1-C
4Alkyl.
The intermediate of formula XII, II and IX can resemble described in the reaction formula 11 by formula XI compound.The imidoether of formula XII can the through type XI nitrile combine in alcoholic solvent (preferably methyl alcohol or ethanol) with 0.1 to 1 normal alkali metal alcoholates (preferably sodium methylate or sodium ethylate) and prepare.Temperature of reaction can be from 0 ℃ to 50 ℃ (preferably room temperature), and reaction was finished after 1 to 48 hour usually.Acid (for example acetate) neutralization is normally used in finishing of reaction, and reaction mixture is concentrated, and is dissolved in (for example ether) in the suitable solvent, filters by-product salt (as, sodium acetate), and filtrate concentrating obtained the imidoether XII, and its is not purified usually just uses.
The intermediate amidine of formula II can the through type XII imidoether and 1.0 to 1.1 normal ammonium salts (for example ammonium chloride, brometo de amonio, amine acetate and ammonium formiate) react in (preferably methyl alcohol or ethanol) or in alcohol-water mixture and prepare.
Temperature of reaction can be from room temperature to used concrete solvent reflux temperature, reaction was finished after 5 hours at 30 minutes usually.Reaction mixture is concentrated, obtain amidine salt (HL
3), be purified with recrystallization method or development method.This amidine salt can be used in the foregoing reaction, or changes into their conjugate base earlier.
Perhaps, the amidine of formula II can be as (Tetra-hedron lett.1990,31,1969-1972) from nitrile XI reagent MeAl(Cl) NH as described in the Garigipati
2Directly preparation.
The ester of formula IX can be prepared by imidoether hydrolysis in the water that contains optional a kind of organic cosolvent of formula XII.Typical reaction comprises the imidoether XII is combined in the organic cosolvent of choosing wantonly with excessive acid (for example sulfuric acid or hydrochloric acid) that the example of organic cosolvent has methyl alcohol, ethanol, tetrahydrofuran (THF) and diox.Temperature of reaction can be from 0 ℃ to used concrete solvent reflux temperature (preferably 0 ℃ to room temperature), reaction was finished in 6 hours usually.
Reaction formula 11
Wherein:
R
20Be C
1-C
4Alkyl,
M
2Be basic metal,
L
3Be negatively charged ion, Cl for example, Br, OAc, or OCHO.
The intermediate of formula XI can utilize method (J.org.chem., 1983,48, the 1375-1377 of Fife according to the explanation in the reaction formula 12; Summary: Heterocycles, 1984,22,2375-2394) the N-oxide compound by formula X I V prepares.As people such as Sakamoto (Chem.Pharm.Bull.1985,33,565-571) and people (Heterocycles.1990 such as Yamanaka, 31,923-967) discussed, there is other modification of several Reissert-Henze reactions to can be used for pyridine and pyrimidine N-oxide compound, so no longer these methods are further gone through.
The N-oxide intermediate of formula X I V can be by with 1 to 1.2 normal suitable oxygenant, and for example 3-chloroperoxybenzoic acid, monoperphthalic acid magnesium, peracetic acid, hydrogen peroxide etc. prepare the compound oxidation of formula VIII.Typical solvent comprises halohydrocarbon (for example methylene dichloride, 1,2-ethylene dichloride and chloroform) and aromatic hydrocarbons (for example benzene and toluene).Temperature of reaction can be from 0 ℃ to used concrete solvent reflux temperature, reaction was finished in 24 hours usually.When Z is N, can form the N-hopcalite; The N-oxide compound of these regional isomerisms all can be used for subsequently the Fife cyanogenation to the intermediate XI.
Reaction formula 12
Many formula X III compounds are that this specialty is known, can prepare with method.Or it is CR that these formula X III compounds are worked as Z
6The time, can prepare with one of several pyridine annulation methods known in the art.Two kinds of such methods have been summarized in the reaction formula 13.
People's such as Chelucci method (J.Heterocyclic Chem.1988,25,1761-1765) comprise use the 2-(2-bromotrifluoromethane)-1,3-two oxa-s penta ring is with N, the alkylation of N-dimethyl hydrazone negatively charged ion, obtain intermediate X VI, it is cyclized into cyclic pyridine X III in the acetate that refluxes (Z is CH; R
3Be H).A kind of effective and safer modification of Cheluccj method, with 1,3-dimethyl-3,4,5,6-tetrahydrochysene-2(1H)-pyrimidone (DMPU) replace deleterious may carcinogenic substance hexamethylphosphoramide (HMPA) as the cosolvent in the alkylated reaction.
(Synthesis 1979 for people such as Kusumi, 221-223) and people such as Koyama (Chem.Pharm.Bull.1983,31, he method 2601-2606) is undertaken by O-allyl group oxime X VII, this material is when 180 ℃ to 200 ℃ following pyrolysis, and (Z is CH to be cyclized into cyclic pyridine X III; R
3Be H).The method of other formation pyridine ring has been discussed in the following document:
Bell et al.(J.Am.Chem.Soc.1991,113,6283-6284); Thummel(Tetrahedron 1991,34,6851-6886); Westerwelle et al.(Chem.Ber.1991,124,571-576); Potts et al.(J.Org.Chem.1982,3027-3038); Ciufolini et al.(J.Am.Chem.Soc.1991,113,8016-8024 and J.Chem.Soc., Chem.Commun.1988,1230-1231);
And Kr
Hnke(Synth.1976,1-24).
The initiator ketone of formula X V is that this specialty is known, can be according to obtaining with the similar method of known steps.Formula X V compound comprises the homologue of indone, Tetralone an intermediate of Sertraline, benzosuberone, benzodihydropyrone, the homologue of thiochromanone, isochromanome, cumarone-3-ketone and other material.
Reaction formula 13
The intermediate of formula X III, when Z is N, can be as described in the reaction formula 14, by the ketone preparation of formula X V.Formula X V compound can with method well known in the art (Hauser etc., Organic Reactions, 1954,8,59-196) change into the derivative X V III of acidylate.These compounds again can be according to the described (Chem.Ber.1957 of people such as Bredereck, 90,942-952) and formamide, or according to the described (Org.Syn.Coll.Vol.1963 of people such as Foster, 4,638-640) react after the desulfurization of Raney nickel changes into pyrimidine X III with the methyl ether reaction or with thiocarbamide.
Or the ketone of formula X V can change into wherein L with methods known in the art
4It is the formula X I X compound of leavings group.The intermediate of formula X I X can be by with thiocarbamide reaction, then carry out the desulfurization of Raney nickel, or react with carbonamidine.Change into intermediate pyrimidine X III (Z=N).
Reaction formula 14
In the formula:
R
20Be C
1-C
4Alkyl; With
L
4Be a leavings group, for example halogen, alkoxyl group, alkyl sulfenyl, dialkyl amido, haloalkyl sulfonyloxy and aryl-sulfonyl oxygen.
Formula I compound, when X and Y are nitrogen, can be according to 15 described preparations of reaction formula.The amidine of formula II can be described according to Schaeffer (J.Org.Chem.1962,27,3608-3613), transform accepted way of doing sth I compound (X=Y=N by imidoether reaction with the formula XX; R
1=R
2).Work as R
1When being the substituting group that connects by heteroatoms, for example halogen and alkoxyl group, this method is inapplicable.
The X and the Y that also show in reaction formula 15 wherein are nitrogen, R
2It is the preparation of the formula I compound of chlorine.Its method is, according to described (Angew.Chem.Int.Ed.Engl.1966 such as Schmelzer, 5,960-961), the amidine of through type II and the reaction of formula XX I compound, or according to the described (Aust.J.Chem.1981 of Harris, 34,623-634 and Synth.1980,841-842), the N-cyano amidine of through type XX II and chlorine methylenimine reactant salt.The N-cyano amidine of formula XX II can be described according to Huffman etc. (J.Org.Chem.1963,28,1812-1816) imidoether of through type XII and cyano group acid amides react and prepare.In addition, can with the method for Bader (J.Org.Chem.1965,30,707-711) prepare other formula I compound (X=Y=N).
Reaction formula 15
R in the formula
20Be C
1-C
4Alkyl.
The compound of formula I is when X is that N and Y are CR
5The time, can be described according to reaction formula 16, by the ester preparation of formula IX.Condensation (the Hauser etc. of the claisen formula between ester and the ketone, Organic Reactions, 1954,8,59-196) and claisen condensation (Hauser etc., Organic Reactions between two different esters, 1942,1,266-302) generation is all suc as formula 1 of XX IV intermediate, and the 3-dicarbonyl compound is well-known in the art.Reaction between the amidine of formula XX IV intermediate and formula XX V can resemble that the front mentions in reaction formula 2 carry out.Formula XX V compound comprises amidine, thiocarbamide, urea, O-alkyl isourea and S alkyl isothiourea.In addition, the R in formula XX IV
2When being a leavings group, for example alkoxyl group, the then R in the product
2To be hydroxyl, it can resemble described in the reaction formula of front, is converted to several other substituting groups.
Reaction formula 16
R in the formula
20Be C
1-C
4Alkyl.
Formula I compound is when X and Y are respectively CR
4And CR
5The time, can be described according to reaction formula 17, by the intermediate nitrile preparation of formula XI.The ketone that organometallic reagent and nitrile addition obtain the representative of formula XX VI is well known in the art.The ketone of formula XX VI can transform accepted way of doing sth XX VII intermediate by method well known in the art, and the reaction of Michael's type takes place for intermediate XX VII and ketone, then (works as L with ammonium acetate
1When being leavings group) or oxyamine (work as L
1When being hydrogen) cyclisation, the pyridine (X=CR of production I
4, Y=CR
5); The example of these methods has been discussed: Jameson et al.(Tetrahedron Lett.1991 in the following document, 32,1999-2002), Potts et al.(J.Am.Chem.Soc.1981,103,3585-3586), with Jones(Comprehensive Heterocyclic Chemistry Vol.2,395-510, Katritzky and Rees, Eds., Pergamon).Similar Michael's type reaction between the ketone of formula XX VI and the formula XX VIII compound, the pyridine (X=CR of production I after cyclisation
4, Y=CR
5).
Reaction formula 17
In the formula: M
3Be alkali or alkaline-earth metal; L
1Be hydrogen or leavings group, for example halogen, alkoxyl group, alkyl sulfenyl, dialkyl amido, haloalkyl sulfonyloxy and aryl-sulfonyl oxygen.
Or formula I compound can utilize transition metal-catalyzed aryl coupled reaction preparation as described in the reaction formula 18.The intermediate of formula XX IX is worked as L
5When being halogen, can utilizing the N-oxide intermediate of formula X IV and halogenating agent to react and prepare, the example of halogenating agent has phosphorus pentachloride, phosphorus oxychloride, tribromo oxygen phosphorus etc.Discussion is similar in typical reaction conditions and the reaction formula 9.The tin alkyl intermediate of formula XXX can be described according to people such as Wursthorn (J.Am.Chem.Soc.1978,100,2779-2789), by replacing L with the trialkyl stannyl sodium reagent
5Make, perhaps, when Z is CR
6The time, by carrying out metal-halogen exchange, make with trialkyl tin halides (for example trialkyl tin chloride) reaction again with lithium alkylide (for example butyllithium).The intermediate stannane of formula XXX and L wherein
5The palladium catalyzed coupling effect that is the formula XX XI compound of halogen has formed formula I compound.Typical palladium catalyst comprises four (triphenyl phosphine) palladium (O) and two (triphenyl phosphine) palladium (II) muriate.Typical solvent comprises aromatic hydrocarbons (for example benzene and toluene), cyclic ethers (for example tetrahydrofuran (THF) is with diox) and dimethyl formamide.Relevant coupled reaction is known in the art, sees following document: Solberg for details
et al.（Acta Chem.Scand.1989，43，62-68）;Undheim
et al.（Heterocycles 1990，30，1155-1193）;Gronowitz
et al.（Chem.Scripta 1986，26，305-309）;Fu et al.
(Tetrahedron Lett.1990,31,1665-8); Bailey(Tetrahedron Lett.1986,27,4407-4410); With Heck(Palladium Reagents in Organic Syntheses, 179-321, Academic 1985).
Perhaps, formula I compound can be described in reaction formula 18, and the similar palladium catalyzed coupling of the aryl stannane of through type XX IX intermediate and formula XX XII is used for preparing.Formula XX XI compound is known in the art, can be according to similar method preparation.Formula XX XII compound then can replace L with the trialkyltin sodium reagent by these compounds
5Prepare.This area the professional will appreciate that, the method for many kinds of aryl coupled reactions is arranged in the document, for example: Mitchell et al.(Tetrahedron
Lett.1991,32,2273-2276); Oae et al.(Acc.Chem.Res.1991,24,202-208 and Adv.Heterocyclic Chem.1990,48,1-63); Tamao et al.(The Chemistry of the Metal-Carbon Bond Vol.4,819-887; Hartley, Ed., Wiley); With Strekowski et al.(J.Heterocyclic Chem.1990,27,1393-1400).
Reaction formula 18
In the formula:
L
5It is leavings group, for example a halogen; R
20Be C
1-C
4Alkyl.
Formula I compound, when wherein Z is nitrogen, can through type X V III or the amidine of formula X I X compound and formula XXX III react and prepare (reaction formula 19).Typical reaction conditions is those conditions that reaction formula 2 and reaction formula 3 are discussed respectively.The amidine of formula XXX III can be with the previous method of discussing in reaction formula 11 by corresponding nitrile preparation known in the art.
Reaction formula 19
In the formula:
L
4Be a leavings group, for example halogen, alkoxyl group, alkyl sulfenyl, dialkyl amido, haloalkyl sulfonyloxy and aryl-sulfonyl oxygen.
Formula I compound is when Z is CR
6The time, can utilize Michael's type reaction of formula X I X intermediate and formula XXX IV compound according to described in the reaction formula 20, then carry out cyclisation and prepare.Further details can be with reference to the discussion of reaction formula 17 with about the reference of this method.The intermediate of formula XXX IV is known in the art, can prepare with similar method.
Reaction formula 20
In the formula:
L
4Be a leavings group, for example halogen, alkoxyl group, alkyl sulfenyl, dialkyl amido, haloalkyl sulfonyloxy and aryl-sulfonyl oxygen.
Formula I compound and formula X III intermediate can be according to the general path of preparing of general introduction in reaction formula 21 and 22.In reaction formula 21, a kind of organometallic compound of formula XXX V and a kind of heterocyclic halides of formula XXX VI in the presence of catalyzer (for example suitable palladium or nickel catalyzator) according to step coupling well-known in the art (with reference to the document in reaction formula 18, listed).Formula XXX V compound is aryl boric acid, aryl stannane, aryl zinc, aryl Grignard compound etc., and they are that this specialty is known.In addition, formula XXX VI compound is haloperidid and halogenated pyrimidine, and they are well known in the art, can prepare with method.Select group A
1And A
2, make between them, can form one or several key, so that constitute specific bridged bond A.Have many kinds of synthetic methods to be used for carrying out the cyclisation of formula I compound and formula X III intermediate, comprise but in be limited to: the condensation reaction of lactonization, lactamization, esterification, Friedel-Craft reaction, carbonyl titanium coupling (McMurray reaction) at a low price, witig reaction, acetal formation.For example, work as A
1Be hydroxyl, A
2Be CH
2CO
2During H, use the lactonization of activator (for example 1,3-dicyclohexyl carbodiimide) to produce wherein A to be-OC(O) CH
2-formula X III and formula I compound.Similarly, work as A
1Be hydroxyl, A
2Be CH
2During Br,, obtain A and be-OCH by carrying out etherification with alkaline purification
2-compound; Work as A
1And A
2Be CH
2C(O) during H, the McMurray reaction produces A and is-CH
2CH=CHCH
2-compound; And work as A
1And A
2When being hydroxyl, with 2, the acetal formation of 2-Propanal dimethyl acetal reaction produces A and is-OC(Me)
2The compound of O-.People such as Fu have reported a specific examples (J.Org.Chem. of reaction formula 21 routes, 1991,56,1683-1685), they utilize the palladium catalysis coupling between aryl-boric acid ester and the aryl halide, then carry out the reaction of anionic Friedel-Craft equivalent, production X III intermediate, wherein Q be phenyl ring, A be-C(O)-, R
3Be that H, Z are CH.The effect of two aryl intermediate XXX V and XXX VI can be exchanged, that is, with the similar aryl halide derivative of XXX V and with the coupling of the similar aromatic heterocycle metallic compound of XXX VI, will produce same formula XXX VII intermediate.
Reaction formula 21
In the formula
M
4Be metal group, for example a Sn(R
20)
3, B(OH)
2, B(OR
20)
2, ZnCl, ZnBr, MgCl, MgBr etc.;
L
5Leavings group, for example a halogen;
L
6Be hydrogen or
; With
A
1And A
2Be to be adapted at producing between them key to constitute the group of bridged bond A.
Reaction formula 22 has illustrated a kind of method, wherein utilizes to be similar to the formation bridged bond A of method elder generation that reaction formula 21 is discussed.Suitable synthetic method includes, but is not limited to: esterification, etherificate, acid amides formation, witig reaction etc.Intermediate XXX IX can transform accepted way of doing sth I compound or formula X III intermediate by intramolecular Vllman reaction or relevant aryl coupling.Formula XXX VIII and formula XXX VI compound are aryl and heteroaryl halogenide, and they are known in the art, can be by similar step preparation.The example of this method can find in following document:
Rebek et al.（J.Am.Chem.Soc.1985，107，7487-7493）; Botteghi et al.（Synth.Commun.1991，21，1819-1823）.
Reaction formula 22
Wherein
L
5And L
7Be leavings group, for example halogen independently;
L
6Be hydrogen or
; With
A
1And A
2Be to be adapted at producing between them key to constitute the group of bridged bond A.
The metal complex of The compounds of this invention comprises and copper, zinc, iron, magnesium or the cationic complex compound of manganese.These complex compounds can make by The compounds of this invention is combined with described metal-salt, association reaction (for example ether or tetrahydrofuran (THF)) in aprotic solvent carries out, and also can be in protonic solvent carries out in the mixture of (for example methyl alcohol) or these solvents.Complex compound can be from solution crystallization and precipitation, perhaps when removing solvent, crystallize out.
Need not to further describe, believe that the professional and technical personnel can utilize the present invention according to the above description in the scope of maximum possible.Therefore, following examples are Illustrative, rather than limit the present invention by any way.
Embodiment 1
6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7]-cyclohepta-[1,2-b] pyridine
Steps A: 6,7,8,9-tetrahydrochysene-5H-benzocyclohepta alkene-5-ketone dimethyl hydrazone
With N, N-dimethylhydrazine (37.51 grams, 624.1 mmoles) is added in ethanol (39 milliliters) solution of the 1-benzosuberone (25.00 grams, 156.0 mmoles) that is stirring under nitrogen atmosphere, the mixture heating up that forms is refluxed spend the night.After cool to room temperature, with the reaction mixture concentrating under reduced pressure.Resistates is dissolved in the ethanol, reconcentration; Repeat above-mentioned steps once with ethanol again, repeat twice, obtain 32.65 gram title hydrazone crude products with methylene dichloride.Go up with 1: 25 ethyl acetate/hexane this material chromatography at silica gel (1000 milliliters), obtain the title compound (28.36 restrain 90%) of yellow oily, it is the mixture of cis and trans-isomer(ide): Rf0.05(silica gel, 1: 25 ethyl acetate/hexane);
200 MHz
1H NMR(CDCl
3): main isomer δ 1.75(m, 4H), 2.61(s, 6H), 2.76(m, 4H), 7.1(dd, 1H), 7.2(m, 2H), 7.5(dd, 1H); And minor isomer δ 1.85(m, 4H), 2.38(s, 6H), 2.45(m, 2H), 2.7(m, 2H), 7.2-7.3(m, 4H).
Step B:6-[2-(1,3-dioxolane-2-yl) ethyl]-6,7,8,9-tetrahydrochysene-5H-benzocyclohepta alkene-5-ketone dimethyl hydrazone
In nitrogen atmosphere with under stirring, with (4.35 milliliters of n-Butyl Lithiums, 2.5M hexane solution, 10.87 mmole) be added to (1.66 milliliters of Diisopropylamines that are chilled to 0 ℃, 11.86 mmole) in the solution of anhydrous tetrahydro furan (11.6 milliliters), make LDA solution, under agitation added product (2.000 grams of steps A in introversive this solution in 15 minutes, 9.886 the solution in tetrahydrofuran (THF) (5 milliliters) mmole) keeps temperature to be lower than 5 ℃.The solution that forms was kept 2 hours down at 0 ℃, be cooled to-78 ℃ then.In this solution, in 15 minutes, add the 2-(2-bromotrifluoromethane)-1, (1.28 milliliters of 3-dioxolane, 10.9 mmole) 1,3-dimethyl-3,4,5, the solution in 6-tetrahydrochysene-2-(1H)-pyrimidone (1.32 milliliters), adding speed should make temperature of reaction remain below-65 ℃, then mixture is kept 1 hour down at-78 ℃.Make reaction mixture rise to room temperature, at room temperature place and spend the night.Water makes slowly stopped reaction of reaction mixture, pours into then (250 milliliters) in the water.With the formed mixture of extracted with diethyl ether three times.With the organic extract NaSO that merges
4Concentrating under reduced pressure after dry upward with 1: 4 ethyl acetate/hexane chromatography, obtains yellow oily title compound (2.765 grams, 92.5%) at silica gel (300 milliliters), and it is single geometrical isomer basically:
Rf0.04(silica gel, 1: 4 ethyl acetate/hexane);
200 MHz
1H NMR（CDCl
3）δ1.35（m，2H），
1.52（m，2H），1.81（m，2H），1.91（m，2H），2.56（s，6H），2.75（m，2H），3.77（m，3H），3.9（m，2H），4.69（t，1H），7.05（m，1H），7.15-7.25（m，3H）.
Step C:6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
Under nitrogen atmosphere with glacial acetic acid (207 milliliters) solution of the title compound of step B (31.23 grams, 103.3 mmoles) reflux 2 hours under agitation.Reaction mixture is chilled to room temperature, concentrating under reduced pressure.Resistates is dissolved in the normal heptane, concentrating under reduced pressure several times so that azeotropic is driven residual acetate away.Resistates is dissolved in the HCl aqueous solution (800 milliliters) of 1N, with 4 parts 200 milliliters extracted with diethyl ether to remove the by product of not expecting.With the 1N NaOH aqueous solution aqueous layer is alkalized to pH9 then.With 3 parts of 200 milliliters of extracted with diethyl ether alkalescence water layers, with the extraction liquid MgSO of these merging
4Drying, concentrating under reduced pressure.Resistates is gone up at silica gel (1200 milliliters) and is used the methylene dichloride chromatography, obtains golden brown oily title compound (12.675 grams, 63%): Rf 0.50(silica gel, 1: 1 ethyl acetate/hexane);
200 MHz
1H NMR（CDCl
3）δ2.20
（pent，2H），2.50（t，2H），2.54（t，2H），7.2（m，2H），7.37（m，2H），7.54（d，1H），7.7（d，1H），8.61（dd，1H）.
Step D:6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine-1-oxide compound
Product (10.17 grams, 52.08 mmoles) to step C under nitrogen atmosphere and room temperature 1, descends dropwise to add 3-chloroperoxybenzoic acid (50-60% in stirring in the solution of 2-ethylene dichloride (130 milliliters), commodity, 19.77 gram, 57.29 mmoles), make reactant at room temperature stir and spend the night.Add 1.5 milliliters of dimethyl sulphides and make the reaction all standing, wash with saturated aqueous sodium carbonate (800 milliliters) after 1.5 hours.The dichloromethane extraction aqueous solution with 5 parts 200 milliliters.With the organic layer MgSO that merges
4Dry back concentrating under reduced pressure, resistates on silica gel (1000 milliliters) obtain the title compound (10.45 restrain 95%) of white solid, fusing point 84-87 ℃: Rf 0.12(silica gel, 1: 20 ethanol/methylene with 1: 40 ethanol/methylene chromatography); 400
MHz
1H NMR（CDCl
3）δ2.1-2.2（m，3H），2.45（m，1H），2.6（m，2H），7.15（m，2H），7.27（m，1H），7.37（m，2H），8.05（m，1H），8.3（t，1H）.
Step e: 6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine-2-formonitrile HCN
Under nitrogen and room temperature, to step D product (8.955 grams, 42.40 mmole) in the solution of anhydrous methylene chloride (85 milliliters), under stirring, in 10 minutes, add earlier (6.22 milliliters of trimethylsilyl cyanide, 4.63 gram, 46.6 mmole), in 10 minutes, add dimethylcarbamyl chloride (4.1 milliliters, 4.8 grams, 44.5 mmoles) after 15 minutes.After at room temperature placing 2 days, with saturated NaHCO
3The aqueous solution (800 milliliters) diluting reaction thing is isolated two-layer.Dichloromethane extraction water layer with 3 parts 200 milliliters.With the organic layer drying (MgSO that merges
4) after, concentrating under reduced pressure, resistates is gone up chromatography with 1: 20 ethyl acetate/hexane at silica gel (900 milliliters), obtains white solid title compound (8.257 grams, 88%), fusing point 65.6-66.5 ℃; Rf 0.07(silica gel, 1: 20 ethyl acetate/hexane);
400 MHz
1H NMR（CDCl
3）δ2.28（pentet.
2H），2.54（t，2H），2.57（t，2H），7.25（m，1H），7.4（m，2H），7.6（d，1H），7.68（d，1H），7.73（m，1H）.
Step F: 6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine-2-carbonyl imido acid methyl esters
Under nitrogen atmosphere and room temperature, to step e product (8.25 grams, 37.45 add sodium methoxide solution (3.0 milliliter 25% commercially available methanol solution, 13.11 mmoles) in stirring down in methyl alcohol mmole) (75 milliliters) solution, reactant at room temperature stirred spend the night.Add glacial acetic acid (0.75 milliliter, 787 milligrams, 13.1 mmoles) and make reaction all standing, concentrating under reduced pressure then.Resistates is developed with ether, filters.Filtrate decompression concentrates, and obtains the thick title compound of light yellow oily solid (11.4 gram), fusing point 91.5-98 ℃: Rf 0.25(silica gel, 1: 30 ethanol/methylene); 400 MHz
1H
NMR（CDCl
3）δ2.26（pentet，2H），2.55（t，4H），4.03（s，3H），7.26（d，1H），7.39（t，1H），7.43（t，1H），7.63（d，1H），7.74（d，1H），7.78（d，1H）.
Step G:6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine-2-carbonyl Imidamide hydrochloride
(2.003 restrain with ammonium chloride under nitrogen atmosphere and room temperature, 37.45 water mmole) (18.3 milliliters) solution is added in the solution of crude product imido-ester (37.45 mmole) in dehydrated alcohol (48.3 milliliters) of step F, and the mixture heating up that forms was refluxed 3 hours.With the reaction mixture cooling, concentrating under reduced pressure concentrates under vacuum at last.Develop resulting solid with acetone (50 milliliters), filter the title compound (8.185 grams, 80%) that obtains white solid, it is not melting below 250 ℃: Rf 0.02(silica gel, 1: 30 ethanol/methylene); 400 MHz
1H NMR
（Me
2SO-d
6）δ2.24（pentet，2H），2.49（t，2H），2.56（t，2H），7.37（m，1H），7.45（m，2H），7.87（m，1H），8.09（d，1H），8.23（d，1H），9.44（s，2H），9.55（s，2H）.
The acetone filtrate decompression is concentrated,, obtain extra white solid title compound (695 milligrams, 7%) with methylene dichloride (10 milliliters) development.
Step H:6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
(2.507 restrain to the step G product that is stirring under nitrogen atmosphere and room temperature, 9.158 add sodium methoxide solution (the commercially available methanol solution of 3.14 milliliter of 25% weight in methyl alcohol mmole) (92 milliliters) earlier, 13.74 mmole), add (1.83 milliliters of Acetylacetaldehyde Dimethyl Acetal then, 1.815 gram, 13.74 mmoles).With the vlil that forms 2 hours, be cooled to room temperature, then concentrating under reduced pressure.Resistates is dissolved in the methylene dichloride, and concentrating under reduced pressure (secondary) again is to remove remaining methyl alcohol.With ethanol/methylene on silica gel (280 milliliter) the chromatography of resistates, obtain yellow solid title compound (2.55 grams, 97%), fusing point 161.5-164.5 ℃ with 1: 50.Flecked with Acetylacetaldehyde Dimethyl Acetal (4% weight).With this solid recrystallization in 1-chlorobutane (45 milliliters)/hexane (25 milliliters), obtain pure title compound (1.990 grams, 76%), be cream-colored granular solids.Fusing point 166-166.5 ℃: Rf 0.25(silica gel, 1: 20 ethanol/methylene);
200 MHz
1H NMR（CDCl
3）δ
2.26（pentet，2H），2.56（t，2h），2.58（t，2H），2.65（s，3H），7.15（d，1H），7.22（dd，1H），7.34（dt，1H），7.41（dt，1H），7.70（d，1H），7.91（dd，1H），8.36（d，1H），8.77（d，1H）.
With the mother liquor concentrating under reduced pressure,, obtain extra pale brown look solid title compound (265 milligrams, 10%) with hexane (8 milliliters)/1-chlorobutane (2 milliliters) development resistates.
Embodiment 2
6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine, with the complex compound of zinc chloride
Under nitrogen atmosphere and room temperature with (0.468 milliliter of the zinc chloride diethyl ether solution of 1M, 63.8 milligram, 0.468 mmole) be added to stirring 6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7]-cyclohepta-[1,2-b] in the solution of pyridine (150 milliliters, 0.52 mmole) in anhydrous tetrahydro furan (8 milliliters).In adition process, form precipitation.After at room temperature 2 hours, with the reaction mixture concentrating under reduced pressure.Develop formed orange solids and concentrating under reduced pressure with tetrahydrofuran (THF), carry out in succession four times, obtain orange solids shape title complex compound, it is not melting below 250 ℃: IR(KBr) 1578,1396,774cm
-1
Embodiment 3
2-(4,6-dimethyl-2-pyrimidyl)-6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
Steps A: the methylene radical 2-[(dimethylamino)]-2,3,4,5-tetrahydrochysene-1H-benzocyclohepta alkene-1-ketone
At nitrogen with under stirring, with 1-benzosuberone (14.01 milliliters, 15.00 grams, 93.62 mmoles) at N, the vlil in the dinethylformamide dimethyl acetal (24.88 milliliters, 22.31 grams, 187.2 mmoles) 26 hours.Reaction mixture is cooled to room temperature, and concentrating under reduced pressure concentrates under vacuum at last.Develop formed orange/yellow solid with hexane (65 milliliters), filter, obtain light yellow solid shape title compound (18.60 grams, 92%), fusing point is 38.5-89.5 ℃: Rf 0.06(silica gel, earlier with 1: 4 ethyl acetate/hexane wash-out, use 1: 2 ethyl acetate/hexane wash-out then); 200 MHz
1H NMR（CDCl
3）δ1.85（pentet，2H），2.34（t，2H），2.76（t，2H），3.13（s，6H），7.11（dd，1H），7.31（m，2H），7.65（dd，1H），7.77（s，1H）.
Step B:2-(4,6-dimethyl-2-pyrimidyl)-6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
Under nitrogen atmosphere and room temperature with 1-(4,6-dimethyl-2-pyrimidyl)-ethyl ketone (212 milligrams, 1.41 mmoles) is added to (316 milligrams of the potassium tert.-butoxides that stirring.2.82 in anhydrous tetrahydro furan mmole) (7 milliliters) solution.After following 2 hours of the room temperature, the product (304 milligrams, 1.41 mmoles) of steps A is once added, reactant at room temperature stirs and spends the night.To wherein adding ammonium acetate (1.087 grams, 14.10 mmoles), add glacial acetic acid (3.5 milliliters) then.Under still head,, distilled out tetrahydrofuran (THF) 4 hours with the reactant heating.After cool to room temperature, with the reactant concentrating under reduced pressure.With saturated aqueous sodium carbonate resistates is diluted, make the mixture of gained be alkalescence (pH10), use twice of chloroform extraction.Using MgSO
4After the drying, with the organic extract liquid concentrating under reduced pressure, resistates is gone up chromatography at silica gel (50 milliliters), earlier with 1: 4 ethyl acetate/hexane wash-out, use 1: 3 ethyl acetate/hexane wash-out then, obtain pale brown look solid title compound, fusing point 120.5-123 ℃: Rf0.27(silica gel, 1: 1 ethyl acetate/hexane);
400 MHz
1H NMR（CDCl
3）δ2.26（pent，
2H），2.57（m，4H），2.60（s，6H），7.03（s，1H），7.22（d，1H），7.34（t，1H），7.41（t，1H），7.69（d，1H），7.95（d，1H），8.32（d，1H）.
Embodiment 4
6,7-dihydro-2-(2-pyridyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
Under nitrogen and room temperature, in the solution of anhydrous tetrahydro furan (23.2 milliliters), add 2-acetylpyridine (0.52 milliliter, 563 milligrams, 4.64 mmoles) to the potassium tert.-butoxide that stirs (1.042 grams, 9.290 mmoles).After at room temperature 2 hours, the once adding of product (1.00 grams, 4.64 mmoles) with embodiment 3 steps A makes reactant at room temperature stir and spends the night.Ammonium acetate (3.58 grams, 46.45 mmoles) and glacial acetic acid (11.6 milliliters) are added in the reactant successively.Under still head,, steam tetrahydrofuran (THF) in 2 hours with the reactant heating.After being cooled to room temperature, with the reactant concentrating under reduced pressure.Water and minimum of chloroform dilution resistates add solid yellow soda ash, are alkalescence (pH10) up to water layer, use three parts of chloroform extraction mixtures then.With the organic extract liquid MgSO that merges
4Dry back concentrating under reduced pressure, resistates is gone up chromatography with chloroform at silica gel (140 milliliters), obtains Vandyke brown oily title compound (750 milligrams, 59%): Rf 0.08(silica gel, chloroform);
400 MHz
1H NMR（CDCl
3）δ2.27
（pent，2H），2.56（t，2H），2.59（t，2H），7.29（m，2H），7.38（t，1H），7.44（t，1H），7.68（d，1H），7.81（t，1H），7.87（d，1H），8.32（d，1H），8.57（d，1H），8.68（d，1H）.
Further wash-out to obtain purity be 65%(weight) extra title compound (245 grams, proofread and correct yield is 13% behind the impurity).
Embodiment 5
6,7-dihydro-2-(6-methyl-2-pyridyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
In nitrogen atmosphere with under stirring, in 10 minutes to 0 ℃ 6,7-dihydro-2-(2-pyridyl)-5H-benzo [6,7] cyclohepta-[1,2-b] (250 milligrams of pyridines, 0.918 mmole) add the lithium methide diethyl ether solution (0.66 milliliter, 20 milligrams, 0.92 mmole) of 1.4M in the solution in anhydrous diethyl ether (4.6 milliliters).Reactant is warming to room temperature, and 1 hour post-heating refluxes and spends the night.After cool to room temperature, slowly add entry and make the reaction all standing.Twice of extracted with diethyl ether water layer used in layering.With the organic layer MgSO that merges
4Concentrating under reduced pressure after dry.In nitrogen atmosphere with under stirring, add saturated potassium permanganate acetone soln in the resistates acetone soln under room temperature, no longer disappear up to purple, then with this mixture process diatomite (Celite
) filter.Filtrate decompression concentrates, and resistates is gone up chromatography with 1: 50 ethyl acetate/hexane at silica gel (50 milliliters), obtains the title compound (10 milligrams, 4%) of white solid earlier, fusing point 144-145 ℃: Rf:0.34(silica gel, 1: 10 ethyl acetate/hexane); 400 MHz
1H NMR(CDCl
3)
δ2.27（pent，2H），2.57（m，4H），2.64（s，3H），7.16（d，1H），7.29（m，1H），7.38（m，1H），7.44（m，1H），7.69（m，2H），7.87（d，1H），8.35（m，2H）.
Further wash-out obtains the initial substance (title compound of embodiment 4,125 milligrams, 50%) of white solid, fusing point 72-73.5 ℃.
Embodiment 6
6,7-dihydro-2-(6-methyl-2-pyridyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyrimidine
Under nitrogen atmosphere and room temperature, with (1.70 milliliters of triethylamines, 1.23 gram, 12.2 mmoles) under stirring, be added to 2-(4,6-dimethyl-2-pyrimidyl)-6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine (1.311 grams, 6.090 mmoles) and 6-methyl-2-pyridine carbonyl Imidamide (1.045 grams, 6.090 in the mixture of hydrochloride mmole) in dehydrated alcohol (15.2 milliliters), mixture heating up is refluxed spend the night then.After cool to room temperature, the concentrating under reduced pressure reactant.With methylene dichloride (80 milliliters) dilution resistates, use saturated sodium bicarbonate aqueous solution (25 milliliters) and water (25 milliliters) to wash successively.These water layers are all used dichloromethane extraction.The organic layer that merges is being used MgSO
4After the drying, concentrating under reduced pressure is gone up chromatography with ethyl acetate at silica gel (350 milliliters), obtains the impure title compound (1.17 gram) of yellow solid shape.This material was with ethyl acetate/dichloromethane (100 milliliters) chromatography on silica gel of 1: 1, chromatography again on neutral I aluminum oxide (100 milliliters) then, earlier with 1: 1 dichloromethane/hexane wash-out, use the methylene dichloride wash-out then, use 1: 1 ethyl acetate/dichloromethane to wash at last, obtain the pure title compound (565 milligrams, 32%) of white solid, fusing point 151-153 ℃: Rf 0.17(silica gel, 1: 20 ethanol/methylene);
200 MHz
1H NMR（CDCl
3）δ
2.31（p，2H），2.57（t，2H），2.60（t，2H），2.74（s，3H），7.27（m，2H），7.45（m，2H），7.73（t，1H），7.90（m，1H），8.42（d，1H），8.78（s，1H）.
Embodiment 7
8-bromo-6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine and 10-bromo-6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
Steps A: 8-bromo-6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine and 10-bromo-6,7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
Under nitrogen atmosphere and room temperature, with N-bromosuccinimide (60.159 grams, 338.00 mmole) under agitation be added to 6 in batches, 7-dihydro-5H-benzo [6,7] cyclohepta-[1,2-b] in the solution of pyridine (60.00 gram, 307.3 mmoles) in trifluoroacetic acid (1025 milliliters), reactant at room temperature stirred 4 days.With the reaction mixture concentrating under reduced pressure, resistates dilutes with the 1N NaOH aqueous solution.Alkaline mixed aqueous solution with 3 parts of ethyl acetate extractions formation.With the organic extract liquid MgSO that merges
4After the drying, concentrating under reduced pressure, resistates obtain the 10-bromine isomer (31.015 grams, 37%) of light brown oily earlier: Rf:0.43(silica gel, methylene dichloride with dichloromethane/hexane (1200 milliliters) chromatography on silica gel of 1: 3);
400 MHz
1H NMR（CDCl
3）δ2.23（pent，2H），2.49（t，4H），7.12（d，1H），7.21（dd，1H），7.46（dd，1H），7.55（dd，1H），7.87（d，1H），8.61（dd，1H）.
Further use 1: 3 dichloromethane/hexane wash-out, use the methylene dichloride wash-out then, obtain the mixture (amounting to 33.00 grams, wherein about 7.68 gram 10-bromine isomer, 17.58 gram 8-bromine isomer and unreacted material of 7.74 grams) of 8-bromine isomer, 10-bromine isomer and unreacted initial substance.Some mixes fraction with 1: 20 ethyl acetate/hexane or 1: 1 dichloromethane/hexane chromatography again on silica gel, obtains 8-bromine isomer (8.35 restrain, 10%, be infected with a small amount of unreacted initial substance): Rf 0.33(silica gel, methylene dichloride);
400 MHz，
1H NMR（C
6D
6）δ1.82
（pent，2H），2.01（t，2H），2.58（t，2H），6.66（t，1H），6.83（t，1H），6.89（d，1H），7.41（d，1H），7.87（d，1H），8.53（d，1H）.
Step B:8-bromo-6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b]-pyridine
Synthetic method (step D to H) according to narration in embodiment 1, the 8-bromine isomer of a part of steps A changed into be infected with 7%6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] title compound of pyridine, it is a yellow solid, and fusing point is 112-116 ℃: Rf:0.07(silica gel, 1: 1 ethyl acetate/hexane);
400 MHz
1H NMR（CDCl
3）δ2.25（pent，2H），2.56（t，2H），2.66（s，3H），2.78（t，2H），7.17（d，1H），7.24（t，1H），7.61（d，1H），7.72（d，1H），7.83（d，1H），8.40（d，1H），8.77（d，1H）.
Step C:10-bromo-6,7-dihydro-2-(4-methyl)-the 2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine
According at the synthetic method described in the embodiment 1 (step D to H), the 10-bromine isomer of a part of steps A is changed into title compound, it is the yellow oily solid, fusing point 137-138 ℃: Rf 0.10(silica gel, 1: 2 ethyl acetate/hexane); 400 MHz
1H NMR（CDCl
3）δ2.25（pent，2H），2.51（t，2H），2.58（t，2H），2.67（s，3H），7.10（d，1H），7.18（d，1H），7.46（d，1H），7.72（d，1H），8.05（s，1H），8.40（d，1H），8.78（d，1H）.
The example of The compounds of this invention is shown among the table 1-9.These compounds change into their conjugation acid salt or metal complex easily.The meaning of dummy suffix notation is as follows:
T-represents uncle c-Pr-cyclopropyl
Sec-represents secondary TMS-three silyls
N-represents positive CO
2The H-hydroxycarbonyl group
NHEt-ethylamino n-Pr-n-propyl
The SPh-thiophenyl t-Bu-tertiary butyl
I-Pr-sec.-propyl O-n-Bu n-butoxy
O-i-Pr-isopropoxy n-Bu-normal-butyl
Bu-butyl n-Hex-n-hexyl
Hex-hexyl sec-Bu-sec-butyl
CN-cyano group s-i-Pr-iprotiazem base
OPh-phenoxy group CO
2The Me-methoxycarbonyl
C-Hex-cyclohexyl S(O) Me-methylsulfinyl
NO
2-nitro S(O)
2The Me-methyl sulphonyl
SEt-ethylmercapto group S(O)
2The Et-ethylsulfonyl
SMe-methylthio group S(O)
2N-Bu-normal-butyl alkylsulfonyl
OH-hydroxyl TBS-tertiary butyl dimethyl silanyl
OMe-methoxyl group Et-ethyl
I-represents different OEt-oxyethyl group
Ph phenyl Pr propyl group
C-representative ring NMe
2Dimethylamino
Me methyl N Et
2Diethylamino
The Ac ethanoyl
Table 1
X Y Z n X Y Z n
N CH CH 1 CH N COEt 3
N CH CH 2 CH N CF 1
N CH CH 3 CH N CF 2
N CH N 2 CH N CF 3
N CH N 3 CH CH CMe 2
N CH N 4 CH CH CMe 3
N CH CMe 3 CH CH CF 2
N CH CF 3 CH CH CF 3
CH N CEt 3 CH CH COEt 3
CH N COMe 3 CH CH CEt 3
CH N CCl 3 CH CH CBr 3
CH N CBr 3 CH CH COMe 3
R
1And R
2Be Me; R
3, R
7And R
8Be H
X Y Z n X Y Z n
N N CH 2 CH COEt N 3
N N CH 3 CH CF N 2
N N N 3 CH CF N 3
N N N 4 CH CMe N 4
N CH CH 2 CH CF CH 3
N CH CH 3 CH CMe CH 3
N CH N 3 CH COMe CH 3
N CH N 4 CH CEt CH 3
CH CCl N 3 CH COEt CH 3
CH CBr N 3 CH CI CH 2
CH CEt N 3 CH CMe CF 3
CH COMe N 3 CH CMe CMe 3
X and Y are CH; Z is N; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H Me 2 c-Pr Me 4
H Me 3 Me F 1
H Me 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X, Y and Z are CH; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H Me 2 c-Pr Me 4
H Me 3 Me F 1
H Me 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X and Z are CH; Y is N; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H c-Pr 2 c-Pr Me 4
H c-Pr 3 Me F 1
H c-Pr 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X is CH; Y and d Z are N; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H c-Pr 2 c-Pr Me 4
H c-Pr 3 Me F 1
H c-Pr 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X is CR
4; R
1Be Me; R
2, R
3, R
7And R
8Be H
Y Z R
4n Y Z R
4n
N CH F 1 CH N CH
2OEt 3
N CH Cl 2 CH N vinyl 3
N CH Br 3 CH CH CH=CF
23
N CH I 4 CH CH OCH
2CH=CH
23
N CH CN 2 CH CH C≡C-Me 3
N CH OH 3 CH CH OCH
2C≡C-Me 3
N CH Me 4 CH CH NH
23
N CH i-Pr 2 CH CH 4-CF
3Ph 3
N CH n-Bu 3 CH CH OPh 3
N N CH
2Cl 4 N CH F 3
N N n-C
4F
92 CH N F 3
N N S-sec-Bu 3 CH CH F 3
CH N S(O)Me 2 N CH Cl 3
CH N S(O)
2Et 3 CH N Cl 3
CH N c-Pr 2 N CH Me 3
CH N O-i-Pr 3 CH N Me 3
CH N OCH
2CF
32
X is CH; R
1And R
2Be Me; R
7And R
8Be H
X Z R
3n X Z R
3n
N CH F 1 CH N C≡CH 3
N CH Cl 2 CH N OCH
2C≡C-Me 3
N CH CN 3 CH CH 4-morpholinyls 3
N CH OH 4 CH CH NEt
23
N CH Me 2 CH CH 2-Me-Ph 3
N CH n-Pr 3 CH CH 4-OCF
2CF
2H-Ph 3
N CH CF
34 CH CH O-3-F-Ph 3
N CH SEt 2 N CH Me 3
N CH S(O)
2Me 3 CH N Me 3
N N 2-Me-c-Pr 4 CH CH Me 3
N N O-n-Bu 2 N CH OMe 3
N N OMe 3 CH N OMe 3
CH N OCHF
22 N CH SMe 3
CH N CH
2OMe 3 CH N SMe 3
CH N CH=CHMe 2 N CH OCHF
23
CH N CH=CCl
23 CH N OCHF
23
CH N OCH(Me)CH=CH
22
X and Y are CH; Z is N; R
3And R
8Be H
R
1R
2R
7n R
1R
2R
7n
Me H 6-F 1 Me Me 3-OCH
2C≡CH 3
Me H 4-Cl 2 Me Me 4-OMe 2
Me H 5-CN 3 Me Me 3-O-i-Pr 3
Me H 5-NO
24 Me Me 4-OCF
23
Me H 4-OH 1 Me Me 5-CH
2OEt 3
Me H 5-CO
2H 2 H H 4-CO
2Me 3
Me H 4-Me 3 H H 6-OCH
2OMe 3
Me H 3-n-Hex 4 H H 4-NHEt 3
Me H 4-CH
2CF
32 H H 5-C(=O)NMe
23
Me H 4-S-i-Pr 3 H Me 4-Ph 3
Me H 5-S(O)
2Et 4 H Me 5-(4-F-Ph) 3
Me Me 4-TMS 2 H CF
34-OPh 3
Me Me 4-c-Hex 3 c-Pr H 5-SPh 3
Me Me 4-Ac 4 Me H 3-Me 3
Me Me 5-CH
2CH=CH
22 Me H 5-Me 3
Me Me 4-OCH
2CH=CHMe 3 Me H 6-Me 3
Me Me 4-C≡C-Me 2
X and Y are CH; Z is N; R
1Be Me; R
3Be H
R
2R
7R
8n R
2R
7R
8n
H 3-F 6-F 2 Me 6-Me 5-Me 3
H 5-Cl 4-Cl 3 Me 4-OMe 5-Me 3
H 5-Me 4-Br 4 Me 4-OCF
35-Me 3
H 4-Me 5-Me 2 Me 3-Cl 5-Cl 3
H 4-Me 5-Me 3 Me 3-F 5-F 3
H 4-Me 5-Me 4 H 4-F H 3
H 5-F 4-Et 2 H 4-Cl H 3
H 6-OMe 4-Et 3 H 4-i-Pr H 3
H 4-Me 3-n-Pr 4 H 4-OCF
3H 3
H 5-Cl 4-CF
32 H 4-OMe H 3
H 3-Br 4-CH
2CF
33 H 4-Et H 3
Me 5-OMe 4-OMe 2 H 4-t-Bu H 3
Me 4-F 5-OEt 3 H 4-TMS H 3
Me 5-Cl 4-OCHF
22 H 4-TBS H 3
Me 4-F 5-Me 3 H 4-I H 3
Me 3-F 5-Me 2 H 4-OEt H 3
Me 3-Me 5-Me 3
X, Y and Z are CH; R
3And R
8Be H
R
1R
2R
7n R
1R
2R
7n
Me H 6-F 1 Me Me 3-OCH
2C≡CH 3
Me H 4-Cl 2 Me Me 4-OMe 2
Me H 5-CN 3 Me Me 3-O-i-Pr 3
Me H 5-NO
24 Me Me 4-OCF
23
Me H 4-OH 1 Me Me 5-CH
2OEt 3
Me H 5-CO
2H 2 H H 4-CO
2Me 3
Me H 4-Me 3 H H 6-OCH
2OMe 3
Me H 3-n-Hex 4 H H 4-NHEt 3
Me H 4-CH
2CF
32 H H 5-C(=O)NMe
23
Me H 4-S-i-Pr 3 H Me 4-Ph 3
Me H 5-S(O)
2Et 4 H Me 5-(4-F-Ph) 3
Me Me 4-TMS 2 H CF
34-OPh 3
Me Me 4-c-Hex 3 c-Pr H 5-SPh 3
Me Me 4-Ac 4 Me H 3-Me 3
Me Me 5-CH
2CH=CH
22 Me H 5-Me 3
Me Me 4-OCH
2CH=CHMe 3 Me H 6-Me 3
Me Me 4-C≡C-Me 2
X, Y and Z are CH; R
1Be Me; R
3Be H
R
2R
7R
8n R
2R
7R
8n
H 3-F 6-F 2 Me 6-Me 5-Me 3
H 5-Cl 4-Cl 3 Me 4-OMe 5-Me 3
H 5-Me 4-Br 4 Me 4-OCF
35-Me 3
H 4-Me 5-Me 2 Me 3-Cl 5-Cl 3
H 4-Me 5-Me 3 Me 3-F 5-F 3
H 4-Me 5-Me 4 H 4-F H 3
H 5-F 4-Et 2 H 4-Cl H 3
H 6-OMe 4-Et 3 H 4-i-Pr H 3
H 4-Me 3-n-Pr 4 H 4-OCF
3H 3
H 5-Cl 4-CF
32 H 4-OMe H 3
H 3-Br 4-CH
2CF
33 H 4-Et H 3
Me 5-OMe 4-OMe 2 H 4-t-Bu H 3
Me 4-F 5-OEt 3 H 4-TMS H 3
Me 5-Cl 4-OCHF
22 H 4-TBS H 3
Me 4-F 5-Me 3 H 4-I H 3
Me 3-F 5-Me 2 H 4-OEt H 3
Me 3-Me 5-Me 3
X and Z are CH; Y is N; R
3And R
8Be H
R
1R
2R
7n R
1R
2R
7n
Me H 6-F 1 Me Me 3-OCH
2C≡CH 3
Me H 4-Cl 2 Me Me 4-OMe 2
Me H 5-CN 3 Me Me 3-O-i-Pr 3
Me H 5-NO
24 Me Me 4-OCF
23
Me H 4-OH 1 Me Me 5-CH
2OEt 3
Me H 5-CO
2H 2 H H 4-CO
2Me 3
Me H 4-Me 3 H H 6-OCH
2OMe 3
Me H 3-n-Hex 4 H H 4-NHEt 3
Me H 4-CH
2CF
32 H H 5-C(=O)NMe
23
Me H 4-S-i-Pr 3 H Me 4-Ph 3
Me H 5-S(O)
2Et 4 H Me 5-(4-F-Ph) 3
Me Me 4-TMS 2 H CF
34-OPh 3
Me Me 4-c-Hex 3 c-Pr H 5-SPh 3
Me Me 4-Ac 4 Me H 3-Me 3
Me Me 5-CH
2CH=CH
22 Me H 5-Me 3
Me Me 4-OCH
2CH=CHMe 3 Me H 6-Me 3
Me Me 4-C≡C-Me 2
X and Z are CH; Y is N; R
1Be Me; R
3Be H
R
2R
7R
8n R
2R
7R
8n
H 3-F 6-F 2 Me 6-Me 5-Me 3
H 5-Cl 4-Cl 3 Me 4-OMe 5-Me 3
H 5-Me 4-Br 4 Me 4-OCF
35-Me 3
H 4-Me 5-Me 2 Me 3-Cl 5-Cl 3
H 4-Me 5-Me 3 Me 3-F 5-F 3
H 4-Me 5-Me 4 H 4-F H 3
H 5-F 4-Et 2 H 4-Cl H 3
H 6-OMe 4-Et 3 H 4-i-Pr H 3
H 4-Me 3-n-Pr 4 H 4-OCF
3H 3
H 5-Cl 4-CF
32 H 4-OMe H 3
H 3-Br 4-CH
2CF
33 H 4-Et H 3
Me 5-OMe 4-OMe 2 H 4-t-Bu H 3
Me 4-F 5-OEt 3 H 4-TMS H 3
Me 5-Cl 4-OCHF
22 H 4-TBS H 3
Me 4-F 5-Me 3 H 4-I H 3
Me 3-F 5-Me 2 H 4-OEt H 3
Me 3-Me 5-Me 3
R
2, R
3, R
7And R
8Be H; X is CR
4
Y Z R
1-R
4n Y Z R
1-R
4n
N CH -(CH
2)
3- 2 CH CH -(CH
2)
4- 2
N CH -(CH
2)
3- 3 CH CH -(CH
2)
4- 3
N CH -(CH
2)
3- 4 CH CH -(CH
2)
4- 4
CH N -(CH
2)
3- 2 N N -(CH
2)
4- 2
CH N -(CH
2)
3- 3 N N -(CH
2)
4- 3
CH N -(CH
2)
3- 4 N CH -CH=CH-CH=CH- 1
CH CH -(CH
2)
3- 2 N CH -CH=CH-CH=CH- 2
CH CH -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 3
CH CH -(CH
2)
3- 4 CH N -CH=CH-CH=CH- 2
N N -(CH
2)
3- 2 CH N -CH=CH-CH=CH- 3
N N -(CH
2)
3- 3 CH N -CH=CH-CH=CH- 4
N CH -(CH
2)
4- 1 CH CH -CH=CH-CH=CH- 2
N CH -(CH
2)
4- 2 CH CH -CH=CH-CH=CH- 3
N CH -(CH
2)
4- 3 CH CH -CH=CH-CH=CH- 4
CH N -(CH
2)
4- 2 N N -CH=CH-CH=CH- 2
CH N -(CH
2)
4- 3 N N -CH=CH-CH=CH- 3
CH N -(CH
2)
4- 4
R
1Be Me; R
3, R
7And R
8Be H; X is CR
4
Y Z R
2-R
4n Y Z R
2-R
4n
N CH -(CH
2)
3- 2 CH N -(CH
2)
4- 3
N CH -(CH
2)
3- 3 CH CH -(CH
2)
4- 2
CH N -(CH
2)
3- 2 CH CH -(CH
2)
4- 3
CH N -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 2
CH CH -(CH
2)
3- 2 N CH -CH=CH-CH=CH- 3
CH CH -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 4
N CH -(CH
2)
4- 2 CH N -CH=CH-CH=CH- 2
N CH -(CH
2)
4- 3 CH N -CH=CH-CH=CH- 3
CH N -(CH
2)
4- 2 CH N -CH=CH-CH=CH- 4
R
1Be Me; R
3, R
7And R
8Be H; Y is CR
5
X Z R
2-R
5n X Z R
2-R
5n
CH N -(CH
2)
3- 2 N CH -(CH
2)
3- 2
CH N -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 3
CH N -CH=CH-CH=CH- 2 N CH -CH=CH-CH=CH- 4
CH N -CH=CH-CH=CH- 3 N N -CH=CH-CH=CH- 2
CH CH -CH=CH-CH=CH- 2 N N -CH=CH-CH=CH- 3
CH CH -CH=CH-CH=CH- 3
Table 2
R
1Be Me; R
2, R
3, R
7And R
8Be H
X Y Z n X Y Z n
N CH CH 1 CH N COEt 3
N CH CH 2 CH N CF 1
N CH CH 3 CH N CF 2
N CH N 2 CH N CF 3
N CH N 3 CH CH CMe 2
N CH N 4 CH CH CMe 3
N CH CMe 3 CH CH CF 2
N CH CF 3 CH CH CF 3
CH N CEt 3 CH CH COEt 3
CH N COMe 3 CH CH CEt 3
CH N CCl 3 CH CH CBr 3
CH N CBr 3 CH CH COMe 3
R
1And R
2Be Me; R
3, R
7And R
8Be H
X Y Z n X Y Z n
N N CH 2 CH COEt N 3
N N CH 3 CH CF N 2
N N N 3 CH CF N 3
N N N 4 CH CMe N 4
N CH CH 2 CH CF CH 3
N CH CH 3 CH CMe CH 3
N CH N 3 CH COMe CH 3
N CH N 4 CH CEt CH 3
CH CCl N 3 CH COEt CH 3
CH CBr N 3 CH CI CH 2
CH CEt N 3 CH CMe CF 3
CH COMe N 3 CH CMe CMe 3
X and Y are CH; Z is N; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H Me 2 c-Pr Me 4
H Me 3 Me F 1
H Me 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X, Y and Z are CH; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H Me 2 c-Pr Me 4
H Me 3 Me F 1
H Me 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X and Z are CH; Y is N; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H c-Pr 2 c-Pr Me 4
H c-Pr 3 Me F 1
H c-Pr 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X is CR
4; R
1Be Me; R
2, R
3, R
7And R
8Be H
Y Z R
4n Y Z R
4n
N CH F 1 CH N CH
2OEt 3
N CH Cl 2 CH N vinyl 3
N CH Br 3 CH CH CH=CF
23
N CH I 4 CH CH OCH
2CH=CH
23
N CH CN 2 CH CH C≡C-Me 3
N CH OH 3 CH CH OCH
2C≡C-Me 3
N CH Me 4 CH CH NH
23
N CH i-Pr 2 CH CH 4-CF
3Ph 3
N CH n-Bu 3 CH CH OPh 3
N N CH
2Cl 4 N CH F 3
N N n-C
4F
92 CH N F 3
N N S-sec-Bu 3 CH CH F 3
CH N S(O)Me 2 N CH Cl 3
CH N S(O)
2Et 3 CH N Cl 3
CH N c-Pr 2 N CH Me 3
CH N O-i-Pr 3 CH N Me 3
CH N OCH
2CF
32
X is CH; R
1And R
2Be Me; R
7And R
8Be H
X Z R
3n X Z R
3n
N CH F 1 CH N C≡CH 3
N CH Cl 2 CH N OCH
2C≡C-Me 3
N CH CN 3 CH CH 4-morpholinyls 3
N CH OH 4 CH CH NEt
23
N CH Me 2 CH CH 2-Me-Ph 3
N CH n-Pr 3 CH CH 4-OCF
2CF
2H-Ph 3
N CH CF
34 CH CH O-3-F-Ph 3
N CH SEt 2 N CH Me 3
N CH S(O)
2Me 3 CH N Me 3
N N 2-Me-c-Pr 4 CH CH Me 3
N N O-n-Bu 2 N CH OMe 3
N N OMe 3 CH N OMe 3
CH N OCHF
22 N CH SMe 3
CH N CH
2OMe 3 CH N SMe 3
CH N CH=CHMe 2 N CH OCHF
23
CH N CH=CCl
23 CH N OCHF
23
CH N OCH(Me)CH=CH
22
X and Z are CH; Y is N; R
3And R
8Be H
R
1R
2R
7n R
1R
2R
7n
Me H 6-F 1 Me Me 3-OCH
2C≡CH 3
Me H 4-Cl 2 Me Me 4-OMe 2
Me H 5-CN 3 Me Me 3-O-i-Pr 3
Me H 5-NO
24 Me Me 4-OCF
23
Me H 4-OH 1 Me Me 5-CH
2OEt 3
Me H 5-CO
2H 2 H H 4-CO
2Me 3
Me H 4-Me 3 H H 6-OCH
2OMe 3
Me H 3-n-Hex 4 H H 4-NHEt 3
Me H 4-CH
2CF
32 H H 5-C(=O)NMe
23
Me H 4-S-i-Pr 3 H Me 4-Ph 3
Me H 5-S(O)
2Et 4 H Me 5-(4-F-Ph) 3
Me Me 4-TMS 2 H CF
34-OPh 3
Me Me 4-c-Hex 3 c-Pr H 5-SPh 3
Me Me 4-Ac 4 Me H 3-Me 3
Me Me 5-CH
2CH=CH
22 Me H 5-Me 3
Me Me 4-OCH
2CH=CHMe 3 Me H 6-Me 3
Me Me 4-C≡C-Me 2
X and Z are CH; Y is N; R
1Be Me; R
3Be H
R
2R
7R
8n R
2R
7R
8n
H 3-F 6-F 2 Me 6-Me 5-Me 3
H 5-Cl 4-Cl 3 Me 4-OMe 5-Me 3
H 5-Me 4-Br 4 Me 4-OCF
35-Me 3
H 4-Me 5-Me 2 Me 3-Cl 5-Cl 3
H 4-Me 5-Me 3 Me 3-F 5-F 3
H 4-Me 5-Me 4 H 4-F H 3
H 5-F 4-Et 2 H 4-Cl H 3
H 6-OMe 4-Et 3 H 4-i-Pr H 3
H 4-Me 3-n-Pr 4 H 4-OCF
3H 3
H 5-Cl 4-CF
32 H 4-OMe H 3
H 3-Br 4-CH
2CF
33 H 4-Et H 3
Me 5-OMe 4-OMe 2 H 4-t-Bu H 3
Me 4-F 5-OEt 3 H 4-TMS H 3
Me 5-Cl 4-OCHF
22 H 4-TBS H 3
Me 4-F 5-Me 3 H 4-I H 3
Me 3-F 5-Me 2 H 4-OEt H 3
Me 3-Me 5-Me 3
Table 3
R
1Be Me; R
2, R
3, R
7And R
8Be H
X Y Z n X Y Z n
N CH CH 1 CH N COEt 3
N CH CH 2 CH N CF 1
N CH CH 3 CH N CF 2
N CH N 2 CH N CF 3
N CH N 3 CH CH CMe 2
N CH N 4 CH CH CMe 3
N CH CMe 3 CH CH CF 2
N CH CF 3 CH CH CF 3
CH N CEt 3 CH CH COEt 3
CH N COMe 3 CH CH CEt 3
CH N CCl 3 CH CH CBr 3
CH N CBr 3 CH CH COMe 3
R
1And R
2Be Me; R
3, R
7And R
8Be H
X Y Z n X Y Z n
N N CH 2 CH COEt N 3
N N CH 3 CH CF N 2
N N N 3 CH CF N 3
N N N 4 CH CMe N 4
N CH CH 2 CH CF CH 3
N CH CH 3 CH CMe CH 3
N CH N 3 CH COMe CH 3
N CH N 4 CH CEt CH 3
CH CCl N 3 CH COEt CH 3
CH CBr N 3 CH CI CH 2
CH CEt N 3 CH CMe CF 3
CH COMe N 3 CH CMe CMe 3
X and Y are CH; Z is N; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H Me 2 c-Pr Me 4
H Me 3 Me F 1
H Me 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H
X and Z are CH; Y is N; R
3, R
7And R
8Be H
R
1R
2n R
1R
2n
H H 2 c-Pr Me 1
H H 3 c-Pr Me 2
H H 4 c-Pr Me 3
H c-Pr 2 c-Pr Me 4
H c-Pr 3 Me F 1
H c-Pr 4 Me Cl 2
H OMe 2 Me Br 3
H SMe 3 Me CN 4
H Cl 4 Me Et 1
H OEt 3 Me OH 2
H Ph 3 H n-Hex 3
Me H 1 H t-Bu 4
Me H 2 H CF
32
Me H 3 Me SMe 3
Me H 4 Me S(O)
2-n-Bu 2
Me Me 1 Me 2-Me-c-Pr 3
Me Me 2 c-Hex H 2
Me Me 3 Me OMe 3
Me Me 4 Me OCH
2CF
32
Me OMe 2 Me OCH
2OMe 3
Me OMe 3 Me CH=CHMe 2
Me OMe 4 OCH
2CH=CH
2H 3
Et H 2 OH Me 2
Et H 3 n-Bu NMe
23
Et H 4 C≡C-Me H 2
CF
3H 3 Me OPh 3
i-Pr H 3 Ph OCH
2C≡CH 2
N-Bu H 3 Me piperidino 3
c-Hex H 3 CH=CCl
2H 2
Ph H 2 NHEt H 3
t-Bu H 3 Me 4-CF
3-Ph 3
OMe H 3 CH
2CH
2OMe S(O)Me 3
SMe H 2 CH
2C≡CH H 3
X is CR
4; R
1Be Me; R
2, R
3, R
7And R
8Be H
Y Z R
4n Y Z R
4n
N CH F 1 CH N CH
2OEt 3
N CH Cl 2 CH N vinyl 3
N CH Br 3 CH CH CH=CF
23
N CH I 4 CH CH OCH
2CH=CH
23
N CH CN 2 CH CH C≡C-Me 3
N CH OH 3 CH CH OCH
2C≡C-Me 3
N CH Me 4 CH CH NH
23
N CH i-Pr 2 CH CH 4-CF
3Ph 3
N CH n-Bu 3 CH CH OPh 3
N N CH
2Cl 4 N CH F 3
N N n-C
4F
92 CH N F 3
N N S-sec-Bu 3 CH CH F 3
CH N S(O)Me 2 N CH Cl 3
CH N S(O)
2Et 3 CH N Cl 3
CH N c-Pr 2 N CH Me 3
CH N O-i-Pr 3 CH N Me 3
CH N OCH
2CF
32
X is CH; R
1And R
2Be Me; R
7And R
8Be H
X Z R
3n X Z R
3n
N CH F 1 CH N C≡CH 3
N CH Cl 2 CH N OCH
2C≡C-Me 3
N CH CN 3 CH CH 4-morpholinyls 3
N CH OH 4 CH CH NEt
23
N CH Me 2 CH CH 2-Me-Ph 3
N CH n-Pr 3 CH CH 4-OCF
2CF
2H-Ph 3
N CH CF
34 CH CH O-3-F-Ph 3
N CH SEt 2 N CH Me 3
N CH S(O)
2Me 3 CH N Me 3
N N 2-Me-c-Pr 4 CH CH Me 3
N N O-n-Bu 2 N CH OMe 3
N N OMe 3 CH N OMe 3
CH N OCHF
22 N CH SMe 3
CH N CH
2OMe 3 CH N SMe 3
CH N CH=CHMe 2 N CH OCHF
23
CH N CH=CCl
23 CH N OCHF
23
CH N OCH(Me)CH=CH
22
Table 4
R
1Be Me; R
2, R
3, R
7And R
1And R
2Be Me; R
3, R
7
R
8Be H; U is S and R
8, be H; U is O
X Y Z n X Y Z n
N CH CH 1 N N CH 2
N CH CH 2 N N CH 3
N CH CH 3 N N N 3
N CH N 2 N N N 4
N CH N 3 N CH CH 2
N CH N 4 N CH CH 3
N CH CMe 3 N CH N 3
N CH CF 3 N CH N 4
CH N CEt 3 CH CCl N 3
CH N COMe 3 CH CBr N 3
CH N CCl 3 CH CEt N 3
CH N CBr 3 CH COMe N 3
CH N COEt 3 CH COEt N 3
CH N CF 1 CH CF N 2
CH N CF 2 CH CF N 3
CH N CF 3 CH CMe N 4
CH CH CMe 2 CH CF CH 3
CH CH CMe 3 CH CMe CH 3
CH CH CF 2 CH COMe CH 3
CH CH CF 3 CH CEt CH 3
CH CH COEt 3 CH COEt CH 3
CH CH CEt 3 CH CI CH 2
CH CH CBr 3 CH CMe CF 3
CH CH COMe 3 CH CMe CMe 3
X and Y are CH; Z is N; R
3And R
8Be H; R
7Be 5-Me; U is S;
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H Me 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Y are CH; Z is N; R
3, R
7And R
8Be H; U is O
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X, Y and Z are CH; R
3And R
8Be H; R
7Be 5-Me; U is O
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H Me 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X, Y and Z are CH; R
3And R
7Be H; R
8Be Me; U is NR
8
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X and Z are CH; Y is N; R
3And R
8Be H; R
7Be 5-Me; U is O
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H c-Pr 2 Me OMe 3
H c-Pr 3 Me OMe 4
H c-Pr 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Z are CH; Y is N; R
3, R
7And R
8Be H; U is S
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X is CR
4; R
1Be Me; R
2, R
3, R
7And R
8Be H; U is NH
Y Z R
4n Y Z R
4n
N CH F 1 CH N CH
2OEt 3
N CH Cl 2 CH N vinyl 3
N CH Br 3 CH CH CH=CF
23
N CH I 4 CH CH OCH
2CH=CH
23
N CH CN 2 CH CH C≡C-Me 3
N CH OH 3 CH CH OCH
2C≡C-Me 3
N CH Me 4 CH CH NH
23
N CH i-Pr 2 CH CH 4-CF
3Ph 3
N CH n-Bu 3 CH CH OPh 3
N N CH
2Cl 4 N CH F 3
N N n-C
4F
92 CH N F 3
N N S-sec-Bu 3 CH CH F 3
CH N S(O)Me 2 N CH Cl 3
CH N S(O)
2Et 3 CH N Cl 3
CH N c-Pr 2 N CH Me 3
CH N O-i-Pr 3 CH N Me 3
CH N OCH
2CF
32
X is CH; R
1And R
2Be Me; R
7And R
8Be H; U is S
X Z R
3n X Z R
3n
N CH F 1 CH N C≡CH 3
N CH Cl 2 CH N OCH
2C≡C-Me 3
N CH CN 3 CH CH 4-morpholinyls 3
N CH OH 4 CH CH NEt
23
N CH Me 2 CH CH 2-Me-Ph 3
N CH n-Pr 3 CH CH 4-OCF
2CF
2H-Ph 3
N CH CF
34 CH CH O-3-F-Ph 3
N CH SEt 2 N CH Me 3
N CH S(O)
2Me 3 CH N Me 3
N N 2-Me-c-Pr 4 CH CH Me 3
N N O-n-Bu 2 N CH OMe 3
N N OMe 3 CH N OMe 3
CH N OCHF
22 N CH SMe 3
CH N CH
2OMe 3 CH N SMe 3
CH N CH=CHMe 2 N CH OCHF
23
CH N CH=CCl
23 CH N OCHF
23
CH N OCH(Me)CH=CH
22
R
2, R
3, R
7And R
8Be H; X is CR
4; U is S
Y Z R
1-R
4n Y Z R
1-R
4n
N CH -(CH
2)
3- 2 CH CH -(CH
2)
4- 2
N CH -(CH
2)
3- 3 CH CH -(CH
2)
4- 3
N CH -(CH
2)
3- 4 CH CH -(CH
2)
4- 4
CH N -(CH
2)
3- 2 N N -(CH
2)
4- 2
CH N -(CH
2)
3- 3 N N -(CH
2)
4- 3
CH N -(CH
2)
3- 4 N CH -CH=CH-CH=CH- 1
CH CH -(CH
2)
3- 2 N CH -CH=CH-CH=CH- 2
CH CH -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 3
CH CH -(CH
2)
3- 4 CH N -CH=CH-CH=CH- 2
N N -(CH
2)
3- 2 CH N -CH=CH-CH=CH- 3
N N -(CH
2)
3- 3 CH N -CH=CH-CH=CH- 4
N CH -(CH
2)
4- 1 CH CH -CH=CH-CH=CH- 2
N CH -(CH
2)
4- 2 CH CH -CH=CH-CH=CH- 3
N CH -(CH
2)
4- 3 CH CH -CH=CH-CH=CH- 4
CH N -(CH
2)
4- 2 N N -CH=CH-CH=CH- 2
CH N -(CH
2)
4- 3 N N -CH=CH-CH=CH- 3
CH N -(CH
2)
4- 4
R
1Be Me; R
3, R
7And R
8Be H; X is CR
4; U is O
Y Z R
2-R
4n Y Z R
2-R
4n
N CH -(CH
2)
3- 2 CH N -(CH
2)
4- 3
N CH -(CH
2)
3- 3 CH CH -(CH
2)
4- 2
CH N -(CH
2)
3- 2 CH CH -(CH
2)
4- 3
CH N -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 2
CH CH -(CH
2)
3- 2 N CH -CH=CH-CH=CH- 3
CH CH -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 4
N CH -(CH
2)
4- 2 CH N -CH=CH-CH=CH- 2
N CH -(CH
2)
4- 3 CH N -CH=CH-CH=CH- 3
CH N -(CH
2)
4- 2 CH N -CH=CH-CH=CH- 4
R
1Be Me; R
3With d R
8Be H; Y is CR
5; U is NR
7; R
7Be Me
X Z R
2-R
5n X Z R
2-R
5n
CH N -(CH
2)
3- 2 N CH -(CH
2)
3- 2
CH N -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 3
CH N -CH=CH-CH=CH- 2 N CH -CH=CH-CH=CH- 4
CH N -CH=CH-CH=CH- 3 N N -CH=CH-CH=CH- 2
CH CH -CH=CH-CH=CH- 2 N N -CH=CH-CH=CH- 3
CH CH -CH=CH-CH=CH- 3
Table 5
R
1Be Me; R
2, R
3, R
7And R
8R
1And R
2Be Me; R
3, R
7With
Be H; U is O R
8Be H; U is S
X Y Z n X Y Z n
N CH CH 1 N N CH 2
N CH CH 2 N N CH 3
N CH CH 3 N N N 3
N CH N 2 N N N 4
N CH N 3 N CH CH 2
N CH N 4 N CH CH 3
N CH CMe 3 N CH N 3
N CH CF 3 N CH N 4
CH N CEt 3 CH CCl N 3
CH N COMe 3 CH CBr N 3
CH N CCl 3 CH CEt N 3
CH N CBr 3 CH COMe N 3
CH N COEt 3 CH COEt N 3
CH N CF 1 CH CF N 2
CH N CF 2 CH CF N 3
CH N CF 3 CH CMe N 4
CH CH CMe 2 CH CF CH 3
CH CH CMe 3 CH CMe CH 3
CH CH CF 2 CH COMe CH 3
CH CH CF 3 CH CEt CH 3
CH CH COEt 3 CH COEt CH 3
CH CH CEt 3 CH CI CH 2
CH CH CBr 3 CH CMe CF 3
CH CH COMe 3 CH CMe CMe 3
X, Y and Z are CH; R
3And R
8Be H; R
7Be 2-Me; U is S
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H Me 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X, Y and Z are CH; R
3And R
8Be H; R
7Be 2-Me; U is O
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X and Z are CH; Y is N; R
3And R
8Be H; R
7Be Me; U is NR
7
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H c-Pr 2 Me OMe 3
H c-Pr 3 Me OMe 4
H c-Pr 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Z are CH; Y is N; R
3, R
7And R
8Be H; U is O
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X is CR
4; R
1Be Me; R
2, R
3, R
7And R
8Be H; U is S
Y Z R
4n Y Z R
4n
N CH F 1 CH N CH
2OEt 3
N CH Cl 2 CH N vinyl 3
N CH Br 3 CH CH CH=CF
23
N CH I 4 CH CH OCH
2CH=CH
23
N CH CN 2 CH CH C≡C-Me 3
N CH OH 3 CH CH OCH
2C≡C-Me 3
N CH Me 4 CH CH NH
23
N CH i-Pr 2 CH CH 4-CF
3Ph 3
N CH n-Bu 3 CH CH OPh 3
N N CH
2Cl 4 N CH F 3
N N n-C
4F
92 CH N F 3
N N S-sec-Bu 3 CH CH F 3
CH N S(O)Me 2 N CH Cl 3
CH N S(O)
2Et 3 CH N Cl 3
CH N c-Pr 2 N CH Me 3
CH N O-i-Pr 3 CH N Me 3
CH N OCH
2CF
32
X is CH; R
1And R
2Be Me; R
7Be H; R
8Be Et; U is O
X Z R
3n X Z R
3n
N CH F 1 CH N C≡CH 3
N CH Cl 2 CH N OCH
2C≡C-Me 3
N CH CN 3 CH CH 4-morpholinyls 3
N CH OH 4 CH CH NEt
23
N CH Me 2 CH CH 2-Me-Ph 3
N CH n-Pr 3 CH CH 4-OCF
2CF
2H-Ph 3
N CH CF
34 CH CH O-3-F-Ph 3
N CH SEt 2 N CH Me 3
N CH S(O)
2Me 3 CH N Me 3
N N 2-Me-c-Pr 4 CH CH Me 3
N N O-n-Bu 2 N CH OMe 3
N N OMe 3 CH N OMe 3
CH N OCHF
22 N CH SMe 3
CH N CH
2OMe 3 CH N SMe 3
CH N CH=CHMe 2 N CH OCHF
23
CH N CH=CCl
23 CH N OCHF
23
CH N OCH(Me)CH=CH
22
Table 6
R
1Be Me; R
2, R
3And R
8Be H; R
7Be 2-Me; U is O
X Y Z n X Y Z n
N CH CH 1 CH N COEt 3
N CH CH 2 CH N CF 1
N CH CH 3 CH N CF 2
N CH N 2 CH N CF 3
N CH N 3 CH CH CMe 2
N CH N 4 CH CH CMe 3
N CH CMe 3 CH CH CF 2
N CH CF 3 CH CH CF 3
CH N CEt 3 CH CH COEt 3
CH N COMe 3 CH CH CEt 3
CH N CCl 3 CH CH CBr 3
CH N CBr 3 CH CH COMe 3
R
1And R
2Be Me; R
3, R
7And R
8Be H; U is S
X Y Z n X Y Z n
N N CH 2 CH COEt N 3
N N CH 3 CH CF N 2
N N N 3 CH CF N 3
N N N 4 CH CMe N 4
N CH CH 2 CH CF CH 3
N CH CH 3 CH CMe CH 3
N CH N 3 CH COMe CH 3
N CH N 4 CH CEt CH 3
CH CCl N 3 CH COEt CH 3
CH CBr N 3 CH CI CH 2
CH CEt N 3 CH CMe CF 3
CH COMe N 3 CH CMe CMe 3
X and Y are CH; Z is N; R
3And R
8Be H; R
7Be 2-Me; U is O
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H Me 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Y are CH; Z is N; R
3, R
7And R
8Be H; U is S
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X and Z are CH; Y is N; R
3And R
8Be H; R
7Be Me; U is NR
7
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H c-Pr 2 Me OMe 3
H c-Pr 3 Me OMe 4
H c-Pr 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Z are CH; Y is N; R
3And R
8Be H; R
7Be 2-i-Pr; U is S
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
Table 7
Wherein V and W are N or C independently.R
1Be Me; R
2, R
3, R
7And R
8Be H; V is N; W is CH
X Y Z n X Y Z n
N CH CH 1 CH N COEt 3
N CH CH 2 CH N CF 1
N CH CH 3 CH N CF 2
N CH N 2 CH N CF 3
N CH N 3 CH CH CMe 2
N CH N 4 CH CH CMe 3
N CH CMe 3 CH CH CF 2
N CH CF 3 CH CH CF 3
CH N CEt 3 CH CH COEt 3
CH N COMe 3 CH CH CEt 3
CH N CCl 3 CH CH CBr 3
CH N CBr 3 CH CH COMe 3
R
1And R
2Be Me; R
3, R
7And R
8Be H; V is CH; W is N
X Y Z n X Y Z n
N N CH 2 CH COEt N 3
N N CH 3 CH CF N 2
N N N 3 CH CF N 3
N N N 4 CH CMe N 4
N CH CH 2 CH CF CH 3
N CH CH 3 CH CMe CH 3
N CH N 3 CH COMe CH 3
N CH N 4 CH CEt CH 3
CH CCl N 3 CH COEt CH 3
CH CBr N 3 CH CI CH 2
CH CEt N 3 CH CMe CF 3
CH COMe N 3 CH CMe CMe 3
X and Y are CH; Z is N; R
3, R
7AndR
8And H; V is N; W is CH
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H Me 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Y are CH; Z is N; R
3And R
8Be H; R
7Be 4-Me; V is CH; W is N
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X, Y and Z are CH; R
3Be R
8Be H; R
7Be 4-Me; V and W are N
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H Me 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X, Y and Z are CH; R
3Be H; R
7Be 4-Me; R
8Be Me; V is N; W is CR
8
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X and Z are CH; Y is N; R
3, R
7And R
8Be H; V is N; W is CH
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H c-Pr 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Z are CH; Y is N; R
3, R
7And R
8Be H; V is CH; W is N
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
R
2, R
3, R
7And R
8Be H; X is CR
4; V is N; W is CH
X Z R
1-R
4n Y Z R
1-R
4n
N CH -(CH
2)
3- 2 CH CH -(CH
2)
4- 2
N CH -(CH
2)
3- 3 CH CH -(CH
2)
4- 3
N CH -(CH
2)
3- 4 CH CH -(CH
2)
4- 4
CH N -(CH
2)
3- 2 N N -(CH
2)
4- 2
CH N -(CH
2)
3- 3 N N -(CH
2)
4- 3
CH N -(CH
2)
3- 4 N CH -CH=CH-CH=CH- 1
CH CH -(CH
2)
3- 2 N CH -CH=CH-CH=CH- 2
CH CH -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 3
CH CH -(CH
2)
3- 4 CH N -CH=CH-CH=CH- 2
N N -(CH
2)
3- 2 CH N -CH=CH-CH=CH- 3
N N -(CH
2)
3- 3 CH N -CH=CH-CH=CH- 4
N CH -(CH
2)
4- 1 CH CH -CH=CH-CH=CH- 2
N CH -(CH
2)
4- 2 CH CH -CH=CH-CH=CH- 3
N CH -(CH
2)
4- 3 CH CH -CH=CH-CH=CH- 4
CH N -(CH
2)
4- 2 N N -CH=CH-CH=CH- 2
CH N -(CH
2)
4- 3 N N -CH=CH-CH=CH- 3
CH N -(CH
2)
4- 4
R
1Be Me; R
3, R
7And R
8Be H; X is CR
4; W is CH; V is N
X Z R
2-R
4n Y Z R
2-R
4n
N CH -(CH
2)
3- 2 CH N -(CH
2)
4- 3
N CH -(CH
2)
3- 3 CH CH -(CH
2)
4- 2
CH N -(CH
2)
3- 2 CH CH -(CH
2)
4- 3
CH N -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 2
CH CH -(CH
2)
3- 2 N CH -CH=CH-CH=CH- 3
CH CH -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 4
N CH -(CH
2)
4- 2 CH N -CH=CH-CH=CH- 2
N CH -(CH
2)
4- 3 CH N -CH=CH-CH=CH- 3
CH N -(CH
2)
4- 2 CH N -CH=CH-CH=CH- 4
R
1Be Me; R
3, R
7And R
8Be H; Y is CR
5; V and W are N
X Z R
2-R
5n X Z R
2-R
5n
CH N -(CH
2)
3- 2 N CH -(CH
2)
3- 2
CH N -(CH
2)
3- 3 N CH -CH=CH-CH=CH- 3
CH N -CH=CH-CH=CH- 2 N CH -CH=CH-CH=CH- 4
CH N -CH=CH-CH=CH- 3 N N -CH=CH-CH=CH- 2
CH CH -CH=CH-CH=CH- 2 N N -CH=CH-CH=CH- 3
CH CH -CH=CH-CH=CH- 3
Table 8
Wherein V and W are N or C independently.R
1Be Me; R
2, R
3, R
7And R
8Be H; V is N; W is CH
X Y Z n X Y Z n
N CH CH 1 CH N COEt 3
N CH CH 2 CH N CF 1
N CH CH 3 CH N CF 2
N CH N 2 CH N CF 3
N CH N 3 CH CH CMe 2
N CH N 4 CH CH CMe 3
N CH CMe 3 CH CH CF 2
N CH CF 3 CH CH CF 3
CH N CEt 3 CH CH COEt 3
CH N COMe 3 CH CH CEt 3
CH N CCl 3 CH CH CBr 3
CH N CBr 3 CH CH COMe 3
R
1And R
2Be Me; R
3, R
7And R
8Be H; V is CH; W is N
X Y Z n X Y Z n
N N CH 2 CH COEt N 3
N N CH 3 CH CF N 2
N N N 3 CH CF N 3
N N N 4 CH CMe N 4
N CH CH 2 CH CF CH 3
N CH CH 3 CH CMe CH 3
N CH N 3 CH COMe CH 3
N CH N 4 CH CEt CH 3
CH CCl N 3 CH COEt CH 3
CH CBr N 3 CH CI CH 2
CH CEt N 3 CH CMe CF 3
CH COMe N 3 CH CMe CMe 3
X, Y and Z are CH; R
3And R
7Be H; R
8Be 5-Me; V is N; W is CH
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H Me 2 Me OMe 3
H Me 3 Me OMe 4
H Me 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X, Y and Z are CH; R
3And R
7Be H; R
8Be 5-Et; V and W are N
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X and Z are CH; Y is N; R
3, R
7And R
8Be H; V is N; W is CH
R
1R
2n R
1R
2n
H H 2 Me Me 3
H H 3 Me Me 4
H H 4 Me OMe 2
H c-Pr 2 Me OMe 3
H c-Pr 3 Me OMe 4
H c-Pr 4 Et H 2
H OMe 2 Et H 3
H SMe 3 Et H 4
H Cl 4 CF
3H 3
H OEt 3 i-Pr H 3
H Ph 3 n-Bu H 3
Me H 1 c-Hex H 3
Me H 2 Ph H 2
Me H 3 t-Bu H 3
Me H 4 OMe H 3
Me Me 1 SMe H 2
Me Me 2
X and Z are CH; Y is N; R
3Be H; R
7Be Me; R
8Be 5-Me; V is CR
7; W is N
R
1R
2n R
1R
2n
c-Pr Me 1 Me OMe 3
c-Pr Me 2 Me OCH
2CF
32
c-Pr Me 3 Me OCH
2OMe 3
c-Pr Me 4 Me CH=CHMe 2
Me F 1 OCH
2CH=CH
2H 3
Me Cl 2 OH Me 2
Me Br 3 n-Bu NMe
23
Me CN 4 C≡C-Me H 2
Me Et 1 Me OPh 3
Me OH 2 Ph OCH
2C≡CH 2
H n-Hex 3 Me piperidino 3
H t-Bu 4 CH=CCl
2H 2
H CF
32 NHEt H 3
Me SMe 3 Me 4-CF
3-Ph 3
Me S(O)
2-n-Bu 2 CH
2CH
2OMe S(O)Me 3
Me 2-Me-c-Pr 3 CH
2C≡CH H 3
c-Hex H 2
X is CR
4; R
1Be Me; R
2, R
3, R
7And R
8Be H; V is N; W is CH
Y Z R
4n Y Z R
4n
N CH F 1 CH N CH
2OEt 3
N CH Cl 2 CH N vinyl 3
N CH Br 3 CH CH CH=CF2 3
N CH I 4 CH CH OCH2CH=CH2 3
N CH CN 2 CH CH C≡C-Me 3
N CH OH 3 CH CH OCH
2C≡C-Me 3
N CH Me 4 CH CH NH
23
N CH i-Pr 2 CH CH 4-CF
3Ph 3
N CH n-Bu 3 CH CH OPh 3
N N CH
2Cl 4 N CH F 3
N N n-C
4F
92 CH N F 3
N N S-sec-Bu 3 CH CH F 3
CH N S(O)Me 2 N CH Cl 3
CH N S(O)Et 3 CH N Cl 3
CH N c-Pr 2 N CH Me 3
CH N O-i-Pr 3 CH N Me 3
CH N OCH
2CF
32
X is CH; R
1And R
2Be Me; R
7Be H; R
8Be 5-Me; V is CH; W is N
X Z R
3n X Z R
3n
N CH F 1 CH N C≡CH 3
N CH Cl 2 CH N OCH
2C≡C-Me 3
N CH CN 3 CH CH 4-morpholinyls 3
N CH OH 4 CH CH NEt
23
N CH Me 2 CH CH 2-MePh 3
N CH n-Pr 3 CH CH 4-OCF
2CF
2H-Ph 3
N CH CF
34 CH CH O-3-F-Ph 3
N CH SEt 2 N CH Me 3
N CH S(O)
2Me 3 CH N Me 3
N N 2-Me-c-Pr 4 CH CH Me 3
N N O-n-Bu 2 N CH OMe 3
N N OMe 3 CH N OMe 3
CH N OCHF
22 N CH SMe 3
CH N CH
2OMe 3 N CH SMe 3
CH N CH=CHMe 2 N CH OCHF
23
CH N CH=CCl
23 CH N OCHF
23
CH N OCH(Me)CH=CH
22
Table 9
Wherein the left side of A links to each other with phenyl ring, and the right and pyridyl ring (are worked as Z=CR
6The time) or link to each other with pyrimidine-ring (when the Z=N).
X and Z are CH; Y is N; R
1Be Me; R
2, R
3, R
7And R
8Be H
-A- -A-
-O- -S(O)
2-CH
2-CH
2-
-NH- -CH
2-S-CH
2-
-S(O)- -CH
2-S(O)
2-CH
2-
-CH(Et)- -CH
2-C(=O)-CH
2-
-C(=O)- -CH
2-C(=O)-O
-C(=O)-CH(Me)- -N(Me)-C(=O)-NH-
-O-CH
2-CH
2-O- -C(Me)
2-CH=CH-
-CH
2-CH
2-S(O)- -CH=CH-CH=CH-
-C(=O)-NH- -CH
2-CH
2-CH
2-O-
-C(Et)
2-CH
2- -S(O)-CH
2-CH
2-CH
2-
-CH
2-CH
2-S(O)
2- -O-C(=O)-CH
2-CH
2-
-CH
2-CH
2-S- -C(=O)-CH=CH-
X, Y and Z are CH; R
1Be Me; R
2, R
3, R
7And R
8Be H
-A- -A-
-S- -CH
2-CH
2-CH
2-NH-
-N(Et)- -CH
2-S(O)-CH
2-
-S(O)
2- -CH
2-N(Me)-CH
2-
-C(Me)
2- -O-C(=O)-CH
2-
-CH
2-C(=O)- -CH
2-O-C(=O)-
-CH
2N(Me)- -C(=O)-O-CH
2-
-C(=O)-O- -CH
2-CH=CH-
-CH
2-CH
2-S(O)
2- -CH
2-CH=CH-CH
2-
-N(Me)-C(=O)- -CH
2-CH
2-CH
2-S-
-CH
2-CH
2-S(O)- -CH
2-CH
2-CH
2-N(Me)-
-CH
2-CH
2-O- -CH
2-O-
-S(O)-CH
2-CH
2- -CH=CH-C(=O)-
X, Y and Z are CH; R
1Be Me; R
2, R
3, R
7And R
8Be H
-A- -A-
-CH=CH- -CH(Me)-O-CH
2-
-O-C(=O)- -CH
2-CH(Me)-CH
2-CH
2-
-C(Me)
2-CH
2- -O-CH
2-CH
2-CH
2-
-CH
2-CH(Me)- -S-CH
2-CH
2-CH
2-
-O-CH
2- -S(O)
2-CH
2-CH
2-CH
2-
-O-CH(Me)- -S(O)
2-C(Me)
2-CH
2-CH
2-
-O-C(Me)
2- -NH-CH
2-CH
2-CH
2-
-N(Me)-CH
2- -N(Me)-CH
2-CH
2-CH
2-
-NH-CH
2- -O-CH
2-O-CH
2-
-S-CH
2- -C(=O)-NH-CH
2-
-S(O)
2-CH
2- -C(=O)-N(Me)-CH
2-
-CH
2-C(Me)
2-CH
2- -C(=O)-N(Et)-CH
2-
-CH(Me)-CH
2-CH
2- -NH-C(=O)-CH
2-
-O-CH
2-O- -N(Me)-C(=O)-CH
2-
-O-CH(Me)-O- -N(Et)-C(=O)-CH
2-
-O-CH(Et)-O- -C(=O)-CH
2-CH
2-
-O-C(Me)
2-O- -CH
2-NH-C(=O)-
-O-CH
2-CH
2- -CH
2-O-CH
2-CH
2-
-O-C(Me)
2-CH
2- -CH
2-CH
2-C(=O)-
-S-CH
2-CH
2- -CH
2-CH
2-NH-
-S-C(Me)
2-CH
2- -CH
2-CH
2-N(Me)-
-NH-CH
2-CH
2- -CH
2-CH
2-N(Et)-
-N(Me)-CH
2-CH
2- -CH
2-C(=O)-NH-
-O-C(=O)-O- -CH
2-C(=O)-N(Me)-
-CH
2-O-CH
2- -CH
2-C(=O)-N(Et)-
X and Y are CH; Z is N; R
1Be Me; R
2, R
3, R
7And R
8Be H
-A- -A-
-CH=CH- -CH(Me)-O-CH
2-
-O-C(=O)- -CH
2-CH(Me)-CH
2-CH
2-
-C(Me)
2-CH
2- -O-CH
2-CH
2-CH
2-
-CH
2-CH(Me)- -S-CH
2-CH
2-CH
2-
-O-CH
2- -S(O)
2-CH
2-CH
2-CH
2-
-O-CH(Me)- -S(O)
2-C(Me)
2-CH
2-CH
2-
-O-C(Me)
2- -NH-CH
2-CH
2-CH
2-
-N(Me)-CH
2- -N(Me)-CH
2-CH
2-CH
2-
-NH-CH
2- -O-CH
2-O-CH
2-
-S-CH
2- -C(=O)-NH-CH
2-
-S(O)
2-CH
2- -C(=O)-N(Me)-CH
2-
-CH
2-C(Me)
2-CH
2- -C(=O)-N(Et)-CH
2-
-CH(Me)-CH
2-CH
2- -NH-C(=O)-CH
2-
-O-CH
2-O- -N(Me)-C(=O)-CH
2-
-O-CH(Me)-O- -N(Et)-C(=O)-CH
2-
-O-CH(Et)-O- -C(=O)-CH
2-CH
2-
-O-C(Me)
2-O- -CH
2-NH-C(=O)-
-O-CH
2-CH
2- -CH
2-O-CH
2-CH
2-
-O-C(Me)
2-CH
2- -CH
2-CH
2-C(=O)-
-S-CH
2-CH
2- -CH
2-CH
2-NH-
-S-C(Me)
2-CH
2- -CH
2-CH
2-N(Me)-
-NH-CH
2-CH
2- -CH
2-CH
2-N(Et)-
-N(Me)-CH
2-CH
2- -CH
2-C(=O)-NH-
-O-C(=O)-O- -CH
2-C(=O)-N(Me)-
-CH
2-O-CH
2- -CH
2-C(=O)-N(Et)-
X and Z are CH; Y is N; R
1Be Me; R
2, R
3, R
7And R
8Be H
-A- -A-
-CH=CH- -CH(Me)-O-CH
2-
-O-C(=O)- -CH
2-CH(Me)-CH
2-CH
2-
-C(Me)
2-CH
2- -O-CH
2-CH
2-CH
2-
-CH
2-CH(Me)- -S-CH
2-CH
2-CH
2-
-O-CH
2- -S(O)
2-CH
2-CH
2-CH
2-
-O-CH(Me)- -S(O)
2-C(Me)
2-CH
2-CH
2-
-O-C(Me)
2- -NH-CH
2-CH
2-CH
2-
-N(Me)-CH
2- -N(Me)-CH
2-CH
2-CH
2-
-NH-CH
2- -O-CH
2-O-CH
2-
-S-CH
2- -C(=O)-NH-CH
2-
-S(O)
2-CH
2- -C(=O)-N(Me)-CH
2-
-CH
2-C(Me)
2-CH
2- -C(=O)-N(Et)-CH
2-
-CH(Me)-CH
2-CH
2- -NH-C(=O)-CH
2-
-O-CH
2-O- -N(Me)-C(=O)-CH
2-
-O-CH(Me)-O- -N(Et)-C(=O)-CH
2-
-O-CH(Et)-O- -C(=O)-CH
2-CH
2-
-O-C(Me)
2-O- -CH
2-NH-C(=O)-
-O-CH
2-CH
2- -CH
2-O-CH
2-CH
2-
-O-C(Me)
2-CH
2- -CH
2-CH
2-C(=O)-
-S-CH
2-CH
2- -CH
2-CH
2-NH-
-S-C(Me)
2-CH
2- -CH
2-CH
2-N(Me)-
-NH-CH
2-CH
2- -CH
2-CH
2-N(Et)-
-N(Me)-CH
2-CH
2- -CH
2-C(=O)-NH-
-O-C(=O)-O- -CH
2-C(=O)-N(Me)-
-CH
2-O-CH
2- -CH
2-C(=O)-N(Et)-
X and Z are CH; Y is N; R
1And R
2Be Me; R
3, R
7And R
8Be H
-A- -A-
-CH=CH- -CH(Me)-O-CH
2-
-O-C(=O)- -CH
2-CH(Me)-CH
2-CH
2-
-C(Me)
2-CH
2- -O-CH
2-CH
2-CH
2-
-CH
2-CH(Me)- -S-CH
2-CH
2-CH
2-
-O-CH
2- -S(O)
2-CH
2-CH
2-CH
2-
-O-CH(Me)- -S(O)
2-C(Me)
2-CH
2-CH
2-
-O-C(Me)
2- -NH-CH
2-CH
2-CH
2-
-N(Me)-CH
2- -N(Me)-CH
2-CH
2-CH
2-
-NH-CH
2- -O-CH
2-O-CH
2-
-S-CH
2- -C(=O)-NH-CH
2-
-S(O)
2-CH
2- -C(=O)-N(Me)-CH
2-
-CH
2-C(Me)
2-CH
2- -C(=O)-N(Et)-CH
2-
-CH(Me)-CH
2-CH
2- -NH-C(=O)-CH
2-
-O-CH
2-O- -N(Me)-C(=O)-CH
2-
-O-CH(Me)-O- -N(Et)-C(=O)-CH
2-
-O-CH(Et)-O- -C(=O)-CH
2-CH
2-
-O-C(Me)
2-O- -CH
2-NH-C(=O)-
-O-CH
2-CH
2- -CH
2-O-CH
2-CH
2-
-O-C(Me)
2-CH
2- -CH
2-CH
2-C(=O)-
-S-CH
2-CH
2- -CH
2-CH
2-NH-
-S-C(Me)
2-CH
2- -CH
2-CH
2-N(Me)-
-NH-CH
2-CH
2- -CH
2-CH
2-N(Et)-
-N(Me)-CH
2-CH
2- -CH
2-C(=O)-NH-
-O-C(=O)-O- -CH
2-C(=O)-N(Me)-
-CH
2-O-CH
2- -CH
2-C(=O)-N(Et)-
Compound of the present invention is used for preparation with the composition that is suitable on the agricultural usually.Fungicidal composition of the present invention comprises at least a at least a above-mentioned formula I compound of effective quantity and the following material: (a) tensio-active agent, (b) organic solvent and (c) at least a solid or liquid diluent.The preparation that is suitable for can be prepared with ordinary method.But they comprise pulvis, granula, pill, solution, suspension, milk sap wet-milling, emulsifiable concentrate, flowable dry etc.Sprayable preparation can dilute in suitable medium, and the sprayed volume when using arrives several hectolitres as per hectare 1.High concentration composition is mainly as using for the intermediate of further preparing usefulness.The active ingredient, thinner and the tensio-active agent that generally contain effective quantity in the preparation, in its consumption probable ranges below, its summation is a 100%(weight).
Weight percentage
Activeconstituents thinner tensio-active agent
But wet-milling 25-90 0-74 1-10
Oil suspension, emulsion, solution 5-50 40-95 0-15
(comprising emulsifiable concentrate)
Dust agent 1-25 70-99 0-5
Granula, erbium material and pill 0.01-99 5-99.99 0-15
High concentration composition 90-99 0-10 0-2
The typical solid thinner is referring to following document: Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey.Following document has been introduced typical liquid diluent and solvent, has listed the purposes of tensio-active agent and recommendation: Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950; McCutcheon ' s Detergents and Emulsifiers Annual, Allured Publ.Corp., Ridgewood, New Jersey, and Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ.Co., Inc., New York, 1964.All preparations can contain minor amounts of additives to reduce foam, caking, burn into microorganism growth etc.
It is well-known preparing these method for compositions.Solution is to make by simply component being mixed.The fine-grained solids composition is by the blending mode and normally grinds in for example hammer mill or fluid energy mill and make.The water dispersible granules can be by making the cohesion of fine powder composition; For example referring to, Cross etc., Pesticide Formulations, Washington, D.C., 1988, PP251-259.Suspension is to prepare with wet milling process; For example, see United States Patent (USP) 3,060,084.Granula and pill can be by spraying to active substance on the preformed particulate vector or utilizing the condensation technique preparation.Referring to Browning, " Agglomeration ", Chemical Engineering, December 4,1967, PP 147-148; Perry ' s Chemical Engineer ' s Handbook, 4th Ed., McGraw-Hill, New York, 1963, PP 8-57 reaches thereafter and WO 91/13546.Pill can be according to United States Patent (USP) 4,172,714 described preparations.Dispersible and the water miscible particle of water can be by German Patent 3,246,493 described preparations.
About the further information of preparation process, referring to United States Patent (USP) 3,235,361, the 6 section 16 row is to the 7th section 19 row and embodiment 10 to 41; United States Patent (USP) 3,309,192, the 5 section 43 row is to the 7th section 62 row and embodiment 8,12,15,39,41,52,53,58,132,138-140,162-164,166,167 and 169-182; United States Patent (USP) 2,891,855, the 3 section 66 row is to the 5th section 17 row and embodiment 1-4;
Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; With Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.
In following examples, all percentage compositions are weight, and all preparations are processing according to a conventional method all.Compound number is referring to the concordance list A of back.
Embodiment A
But wet-milling
Compound 1 65.0%
4-dodecylphenol polyglycol ether 2.0%
Sodium lignosulfonate 4.0%
Sodium silicoaluminate 6.0%
Polynite (incinerating) 23.0%
Embodiment B
Granula
Compound 1 10.0%
Attapulgite particle (low volatile, 0.71/0.30 millimeter; USS screen size 25-50) 90.0%
Embodiment C
The pill of extruding
Compound 1 25.0%
Anhydrous sodium sulphate 10.0%
Calcium lignosulfonate crude product 5.0%
Sodium alkyl naphthalene sulfonate 1.0%
Calcium/magnesium wilkinite 59.0%
Embodiment D
Emulsifiable concentrate
Compound 1 20.0%
The blend 10.0% of oil-soluble sulfonic acid salt and Soxylat A 25-7
Isophorone 90.0%
Compound of the present invention can be used as plant disease controlling agent and uses.Therefore; the invention still further relates to the method for the Plant diseases that a kind of control causes by fungal plant pathogen, comprise the fungicidal composition of using a kind of formula I compound of effective quantity or containing this compound to the plant that will protect or its part or the seed that will protect or seedling.Compound of the present invention and composition provide the control of the disease that the broad spectrum fungus phytopathogen is caused, and these pathogenic agent belong to basidiomycetes, ascomycetes, oomycetes and imperfect fungi.They are effective for the Plant diseases of control wide spectrum, particularly for the blade pathogenic agent of ornamental plant, vegetables, field crop, cereal and fruit crop.These pathogenic agent comprise that the living single shaft of grape is mould, phytophthora infestans, the tobacco downy mildew, the false downy mildew of Cuba, the melon and fruit corruption is mould, alternaria brassica, the withered septoria musiva of grain husk, ball seat tail spore, Semen arachidis hypogaeae tail spore, climing trichobacteria of false young mistress Chard dish is given birth to the tail spore, Botrytis cinerea, fruit gives birth to chain sclerotinia sclerotiorum, Pyricularia oryzae, little tail bundle is mould, venturia inaequalis, the standing grain powdery mildew, grape snag shell bacterium, Puccinia recondita, puccinia graminis, coffee camel spore rest fungus, bar shaped handle rest fungus, Semen arachidis hypogaeae handle rest fungus, dry thread Pyrenomycetes, the monofilament shell, point sickle spore, Garden Dahlia wheel branch spore, the melon and fruit corruption is mould, big male epidemic disease is mould and with these pathogenic agent other Pseudomonas and the bacterial classification of substantial connection are arranged.
Compound of the present invention also can mix with one or more other sterilant, mycocide, nematocides, bactericide, miticide, semiochemicals, repellent, attractive substance, pheromone, ingest stimulant or other bioactive compounds, forms the polycomponent agricultural chemicals with agricultural protection effect more widely.The compounds of this invention can be prepared other agricultural protectant example therewith to be had: sterilant, for example put phosphorus for a long time, carbofuran, tetrachlorvinphos, the Malathion, methyl 1, methomyl, chlordimeform, diazinon, its U.S. spirit (deltamethrin) of moral, thioxamyl, kill the chrysanthemum ester, Ai Sifen valerate (esfenvalerate), TH-6040, Entocon ZR 515, Bu Pulufeijin (buprofezin), sulphur two carbon (thiodicarb), Ortho 12420, R-1582, Chlorpyrifos 94, Rogor, Fei Pulongni (fipronil), fluorine Fen Pulong (flufenprox), Dyfonate, propylamine phosphorus, methidathion, acephatemet, R-1504, phosphamidon, the excellent phosphorus that kills, Aphox, phorate, Terbufos, Dipterex, methoxychlor, two fragrant spirits (bifenthrin), biphenyl ester (biphenate) match fluorine spirit (cyfluthrin), divide and pounce on the chrysanthemum ester, ester in the fluorine (fluvalinate), fluorine match spirit (flucythrinate), special Latin America's spirit (tralomethrin), Metaldehyde and tubatoxin; Mycocide, for example derosal, thiuram, dodine, maneb, chloroneb, F-1991, Sai Moni (Cymoxanil), sweet smell must (fenpropidine), sweet smell must excellent (fenpropimorph), cycloheximide triazole, Vancide 89, thiophanate methyl, Apl-Luster, phosethyl Al, m-tetrachlorophthalodinitrile, the chlorine ammonium nitrate, metalaxyl, Difolatan, different third is fixed, oxygen enemy bacterium (oxadixyl), vinclozolin, kasugamycin, Mai Dingni (myclobutanil), Te Bukena azoles (tebuconazole), enemy's Fen Kena azoles (difenoconazole), enemy's Ni Kena azoles (diniconazole), fluorine Kui Kena azoles (fluquinconazole), different Pu Kena azoles (ipconazole), Mei Tekena azoles (metconazole), penta can receive azoles (Penconazole), third can receive azoles (Propiconazole), list can be received azoles (Uniconazole), fluorine Sanya excellent (flutriafol), Prochloraz, Pai Lifen (pyrifenox), fenarimol, Triabimeno I, two crohn's disease azoles (diclobutrazol), Cupravit, Furalaxyl, Phaltan, azoles is drawn in the fluorine match, miewensu, two chromium gold (diclomezine), Hinosan, Fujione, clothing Pu Benfu (iprobenfos), Mi Puluoni (mepronil), Neo-Asozin, five match clones (pencycuron), thiabendazole, Pai Luokelong (pyroquilon), tricyclazole, validamycin and fluorine Te Lanni (flutolanil); Nematocides, for example go out prestige, Nemacur and Fu Saitan (fosthietan) of sulfone; Bactericide, for example terramycin, Streptomycin sulphate and three alkali blue vitriol; Miticide, for example Niagara 9044, chinomethionate, G-23922, kelthane, Hooker HRS 16, cyhexatin, six thiophenes restrain this (hexythiazox), U-36059, propargite, Te Bufenpai rad (tebufenpyrad) and fenbutatin oxide; And biological reagent, for example Bacillus thuringiensis, baculovirus and avermectins B.
In some situation, similar to prevention and treatment range, but other different mycocide of the mode of action is used in combination, for control resistance fungi particularly advantageous.
Control of plant disease is normally by to the plant part that will protect; for example root, stem, leaf, fruit, seed, stem tuber or bulb; or to the plant-growth that will protect in medium (soil or sand ground) wherein, before introduced disease or use later on that the The compounds of this invention of effective quantity realizes.Also can with compound administration on seed with protection seed and seedling.
These compounds have rate of application can be subjected to a lot of Effect of Environmental, should determine under actual service conditions, when with from being less than 1 gram/hectare when the rate of application of 5000 gram/hectare activeconstituentss is handled, leaf are protected.When handling kind of a period of the day from 11 p.m. to 1 a.m, can protect seed and seedling usually with the rate of application of every kilogram of seed 0.1 to 10 gram.
Following test has confirmed the preventing efficiency of The compounds of this invention to concrete pathogenic agent.Yet the provide protection that these compounds are prevented and treated pathogenic agent is not limited to these kinds.About the explanation of compound referring to concordance list A.
Earlier test compound is dissolved in the acetone, its quantity equals 3% of final volume, is suspended in the concentration of 200ppm subsequently and contains 250ppm tensio-active agent Trem
The 014(polyol ester) in the purified water.Then formed test suspension is used for following test.
Test A
Test suspension is sprayed onto the degree of trickling on wheat seedling.Next day inoculated wheat seeding with standing grain powdery mildew (former dose of wheat powdery mildew) spore powder, cultivates 7 days down in 20 ℃ in the growth case, then degree of disease defined the level.
Test B
Test suspension is sprayed onto the degree of trickling on wheat seedling.Next day inoculated wheat seeding with the spore suspension of the sick rest fungus of concealment (agent of wheat rust leaf disease cause of disease), cultivates 24 hours down in 20 ℃ in saturated atmosphere, moves on to then in the growth case and cultivates 6 days at 20 ℃, after this degree of disease defined the level.
Test C
Test suspension is sprayed onto the degree of trickling on the rice seedling.Next day inoculated seedling with the spore suspension of Pyricularia oryzae (agent of rice blast cause of disease), cultivates 24 hours down in 27 ℃ in saturated atmosphere, moves to then in the growth case and cultivates 5 days at 30 ℃, after this degree of disease defined the level.
Test D
Test suspension is sprayed onto the degree of trickling on tomato seedling.Next day inoculated seedling with the spore suspension of phytophthora infestans (tomato and potato late blight pathogenic agent), cultivates 24 hours under saturated atmosphere at 20 ℃, moves to then in the growth room to cultivate 5 days at 20 ℃, after this degree of disease defined the level.
Test E
Test suspension is sprayed onto the degree of trickling on grape seedling.The spore suspension that next day given birth to single shaft mould (downy mildew of garpe pathogenic agent) with grape is inoculated seedling, under saturated atmosphere, cultivated 24 hours in 20 ℃, move in the growth room and cultivated 6 days down, in saturated atmosphere, cultivated 24 hours down then, after this degree of disease is defined the level in 20 ℃ at 20 ℃.
Test F
Test suspension is sprayed onto the degree of trickling on cucumber seedling.Next day, cultivated 48 hours under saturated atmosphere at 20 ℃ the seedling inoculation with Botrytis cinerea (pathogenic agent of various crop gray mold), moved in the growth case to cultivate 5 days at 20 ℃, then degree of disease defined the level.
Concordance list A
Test A-F the results are shown in the table 1.In this table, grade 100 expressions 100% prevent and treat disease, 0 expression of grade no preventing efficiency (with respect to control group).The NT=not test (N.T.).
Concordance list A
A, oil
1The HNMR data rows is in concordance list C.
B, 97% compound+3% dimethyl formamide.
C, 90% compound+10%2-[(dimethylamino) methylene radical]-3, the naphthalenone of 4-dihydro-1(2H).
D, 93% compound+7% compound 1.
Concordance list B
Compound number MI
mA Y Z R
1R
2R
3R
7R
8Fusing point (℃)
24 ZnCl
2-(CH
2)
3- N CH Me H H H H >250
Concordance list C
Compound number
1H NMR data a
9 2.30(p,2H),2.58(t,2H),2.63(t,2H),2.76(s,3H),
7.25(m,1H),7.40(m,3H),7.85(t,1H),7.92(d,1H),
8.56(d,1H),8.83(d,1H)
15 3.03(s,4H),7.28(dd,1H),7.42(m,3H),7.87(t,1H),
8.54(d,1H),8.66(d,1H),8.76(s,1H),8.83(d,1H)
17 2.44(s,3H),2.68(s,3H),3.00(s,4H),7.09(s,1H),
7.29(m,1H),7.43(m,2H),8.28(s,1H),8.54(m,1H),
8.74(s,1H)
2.77(s,3H),4.01(s,2H),7.29(d,1H),7.55(m,2H),
7.65(d,1H),7.79(t,1H),8.32(d,1H),8.47(d,1H),
9.04(s,1H)
A.
1The HNMR data are unit with ppm, and downfield is a standard with the tetramethylsilane.The coupling situation is expressed as follows: (s) unimodal, (d) bimodal, (t) triplet, (q) quartet, (p) quintet, (m) multiplet, (dd) two bimodal.Except as otherwise noted, all molten CDCl of sample
3In.
Table 1
Compound number test A test B test C test D test E test F
1 86 100 93 75 47
*99
2 100 100 99 61
*91 99
3 94 97 74 87 100 84
4 27 32 18 15
*24 14
5 98 97 94 88 100
*83
6 94 91 67 95 63 72
7 95 98 89 17 100 83
8 100 55 90 0 96 10
12 97 86 77 72 76 80
13 73 95 75 92 100 28
14 37 42 39 0 100 0
15 94 99 60 32 100 42
16 90 97 60 79 97 63
17 21 92 0 NT 97 0
18 61 85 53 0 61 94
19 72 90 0 NT 91 6
20 89 79 0 0 63 7
21 0 82 94 8
*70 0
24 39
*83
*88
*0
*89
*90
*
*Compound sprays with the concentration of 40ppm.
Claims (9)
1, the formula I compound that comprises all geometrical isomers and steric isomer, and agricultural goes up salt and the metal complex that is suitable for
In the formula:
X is N or CR
4
Y is N or CR
5
Z is N or CR
6
Q is condensed benzene, naphthalene, thiophene, furans, pyrroles, pyridine or pyrimidine ring, and they separately can be randomly by R
7And R
8Replace;
A is abutment-G
1-G
2-G
3-G
4-, G wherein
1, G
2, G
3Or G
4Be O, S (O) p, NR independently
9, CR
10R
11, C (=O), direct key, perhaps a G
1-G
2, G
2-G
3Or G
3-G
4Can form together-CH=CH-; Make G
1, G
2, G
3And G
4In at least one be not direct key;
R
1, R
2, R
3And R
4Be H, halogen, cyano group, hydroxyl, C independently
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, randomly use 1-2 methyl substituted C
3-C
6Cycloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
4Alkenyl, C
2-C
4Halogenated alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, NR
12R
13, randomly use R
14The phenyl or the phenoxy group that replace; Or R
1And R
4, R
2And R
4Or R
2And R
5Can form together-(CH
2)
3-,-(CH
2)
4-or a condensed benzyl ring;
R
5And R
6Be H, halogen, C independently
1-C
2Alkyl or C
1-C
2Alkoxyl group;
R
7Be halogen, cyano group, nitro, hydroxyl, hydroxycarbonyl group, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, (C
1-C
4Alkyl)
3Silyl, C
3-C
6Cycloalkyl, C
2-C
5Alkyl-carbonyl, C
2-C
4Alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
5Alkoxy carbonyl, C
2-C
4Alkoxyalkoxy group, NR
15R
16, C (=O) NR
17R
18Or randomly use R separately
19The phenyl, phenoxy group or the thiophenyl that replace;
R
8And R
14Be 1-2 halogen, 1-2C independently of one another
1-C
3Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
R
9And R
10And R
11Be H or C independently
1-C
2Alkyl;
R
12, R
13, R
15, R
16, R
17And R
18Be H or C independently of one another
1-C
2Alkyl; Or R
12And R
13, R
15And R
16Or R
17And R
18Can form a piperidino-(1-position only), pyrrolidyl and morpholino ring with that nitrogen-atoms that they are attached thereto;
R
19Be halogen, C
1-C
2Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
P is 0,1 or 2;
Condition is:
ⅰ) work as G
1, G
2, G
3Or G
4In any one when being O, then they not with O or the direct Cheng Jian of S (O) p;
ⅱ) work as G
1, G
2, G
3Or G
4In any one is S (O) or S (O)
2The time, they not with C (=O) direct Cheng Jian;
ⅲ) the heteroatomic overall number that contains in the ring of A is no more than 2;
ⅳ) when X, Y and Z be that CH, A are CH
2, Q is the unsubstituted benzene of condensed, R
1And R
2When being H, R then
3It or not unsubstituted phenyl; With
ⅴ) these compounds are not 2-[4,6-two (trichloromethyl)-1,3,5-triazines-2-yl]-1,10-phenanthroline or 2-(2-pyridyl)-1,10-phenanthroline.
2, the compound of claim 1, wherein A is an abutment that is selected from following group:
-CR
10R
11-;-G-;
-（CR
10R
11-CR
10R
11）-;-（G-CR
10R
11）-;
-（CH＝CH）-;-[O-C（＝O）]-;-[NR
9-C（＝O）]-;
-（CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11）-;-（CR
10R
11-CH＝CH）-;
-（O-CR
10R
11-O）-;-[O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）]-;-[C（＝O）-CH＝CH]-;
-[O-C（＝O）-O]-;-[NR
9-C（＝O）-NR
9]-;
-（CR
10R
11-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-CR
10R
11 -CH=CH ）-;
-（CR
10R
11-CH＝CH-CR
10R
11）-;
-（CH＝CH-CH＝CH）-;-（O-CR
10R
11-O-CR
10R
11）-;
-（O-CR
10R
11-CR
10R
11-O）-;
-[O-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-NR
9-C(=O)-CR
10R
11]-; With
-[CR
10R
11-CR
10R
11-NR
9-C（＝O）]-;
So A forms a 5-8 unit ring with the atom that is connected; With the directivity of A can be that its left side and Q ring key close, the right and pyridyl ring (are worked as Z=CR
6The time) or pyrimidine-ring (when Z=N) bonding, the perhaps left side of A and pyridyl ring or pyrimidine-ring bonding, the right and Q bonding; G is O, S(O) p, NR
9Or C(=O).
3, the compound of claim 2, wherein:
X is CR
4;
Y is N or CH;
Z is N or CH; With
A is an abutment that is selected from following group:
-（CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11）-;-（CH＝CH）-;-[O-C（＝O）]-;
-[NR
9-C（＝O）]-;
-（CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11）-;-（CR
10R
11-CH＝CH）-;
-（O-CR
10R
11-O）-;-[O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）]-;-[C（＝O）-CH＝CH]-;
-[O-C(=O)-O]-; With-[NR
9-C(=O)-NR
9]-.
4, the compound of claim 3, wherein:
Q is condensed benzene, thiophene, furans or a pyridine ring, and they can randomly use R separately
7And R
8Replace;
A is selected from following group:
-（CH
2-CH
2）-;-[CH
2-C（＝O）]-;-（CH＝CH）-;
-[C（＝O）-O]-;-[C（＝O）-NR
9]-;
-（CH
2-CH
2-CH
2）-;-（O-CH
2-O）-;
-（CH
2-CH
2-O）-;-[CH
2-CH
2-S（O）
p]-;
-（CH
2-CH
2-NR
9）-;-（CH
2-O-CH
2）-;
-[CH
2-S（O）
P-CH
2]-;-（CH
2-NR
9-CH
2）-;
-[O-C（＝O）-O]-;
R
1, R
2, R
3And R
4Be H, halogen, C independently
1-C
4Alkyl, C
1-C
4Haloalkyl, cyclopropyl, C
1-C
4Alkoxyl group or C
2-C
3Alkynyl; With
R
7Be halogen, cyano group, C
1-C
4Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy or C
2-C
4Alkoxyalkoxy group.
5, the compound of claim 4, wherein:
Q is one can randomly use R
7And R
8The fused benzene rings that replaces; With
A is selected from following group:
-（CH
2-CH
2）-;-（CH＝CH）-;-[C（＝O）-O]-;
-[C（＝O）-NR
9]-;-（CH
2-CH
2-CH
2）-;
-（O-CH
2-O）-;-（CH
2-CH
2-O）-;
-[CH
2-CH
2-S（O）
p]-;-（CH
2-CH
2-NR
9）-;
-(CH
2-O-CH
2)-;-[CH
2-S(O)
P-CH
2]-and
-（CH
2-NR
9-CH
2）-。
6, a kind of compound of claim 5, promptly 6,7-dihydro-2-(4-methyl-2-pyrimidyl)-5H-benzo [6,7] cyclohepta-[1,2-b] pyridine.
7, a kind of fungicide composition, wherein contain the formula I compound of effective quantity or its agricultural goes up salt or the metal complex that is suitable for, and at least a in the following material: (a) tensio-active agent, (b) organic solvent, (c) at least a solid or liquid diluent, the formula I is
In the formula:
X is N or CR
4;
Y is N or CR
5;
Z is N or CR
6;
Q is condensed benzene, naphthalene, thiophene, furans, pyrroles, pyridine or pyrimidine ring, and they can randomly use R separately
7And R
8Replace;
A is an abutment that is selected from following group:
-CR
10R
11-;-G-;-（CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11）-;-（CH＝CH）-;-[O-C（＝O）]-;
-[NR
9-C（＝O）]-;-（CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11）-;-（CR
10R
11-G-CR
10R
11）-;
-（CR
10R
11-CH＝CH）-;-（O-CR
10R
11-O）-;
-[O-C（＝O）-CR
10R
11]-;-[CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11]-;-[CR
10R
11-NR
9-C（＝O）]-;
-[C（＝O）-CH＝CH]-;-[O-C（＝O）-O]-;
-[NR
9-C（＝O）-NR
9]-;
-（CR
10R
11-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（G-CR
10R
11-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-G-CR
10R
11-CR
10R
11）-;
-（CR
10R
11-CR
10R
11-CH＝CH）-;
-（CR
10R
11-CH＝CH-CR
10R
11）-;-（CH＝CH-CH＝CH）-;
-（O-CR
10R
11-O-CR
10R
11）-;
-（O-CR
10R
11-CR
10R
11-O）-;
-[O-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-O-C（＝O）-CR
10R
11]-;
-[CR
10R
11-CR
10R
11-O-C（＝O）]-;
-[NR
9-C（＝O）-CR
10R
11-CR
10R
11]-;
-[CR
10R
11-NR
9-C（＝O）-CR
10R
11]-;
-[CR
10R
11-CR
10R
11-NR
9-C（＝O）]-;
So the atom that A is connected with it forms a 5-8 unit ring together; The directivity of A can be that its left side and Q ring key close, and the right and pyridyl ring (are worked as Z=CR
6The time) or pyrimidine-ring (when Z=N) bonding, the perhaps left side and pyridyl ring or pyrimidine-ring bonding, the right and Q bonding;
G is O, S(O) p, NR
9Or C(=O);
P is 0,1 or 2;
R
1, R
2, R
3And R
4Be H, halogen, cyano group, hydroxyl, C independently of one another
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, can be randomly with 1-2 methyl substituted C
3-C
6Cycloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
4Alkenyl, C
2-C
4Halogenated alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, NR
12R
13, randomly can be R
14The phenyl or the phenoxy group that replace; Or R
1And R
4, R
2And R
4Or R
2And R
5Can form together-(CH
2)
3-,-(CH
2)
4-or the condensed benzyl ring;
R
5And R
6Be H, halogen, C independently
1-C
2Alkyl or C
1-C
2Alkoxyl group;
R
7Be halogen, cyano group, nitro, hydroxyl, hydroxycarbonyl group, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, (C
1-C
4Alkyl)
3Silyl, C
3-C
6Cycloalkyl, C
2-C
5Alkyl-carbonyl, C
2-C
4Alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
5Alkoxy carbonyl, C
2-C
4Alkoxyalkoxy group, NR
15R
16, C(=O) NR
17R
18; Or randomly use R separately
19The phenyl, phenoxy group or the thiophenyl that replace;
R
8And R
14Be 1-2 halogen, 1-2C independently of one another
1-C
3Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
R
9, R
10And R
11Be H or C independently of one another
1-C
2Alkyl;
R
12, R
13, R
15, R
16, R
17And R
18Be H or C independently of one another
1-C
2Alkyl; Perhaps R
12And R
13, R
15And R
16Or R
17And R
18Can form a piperidino-(1-position only) with the nitrogen-atoms that they connected, pyrrolidyl or morpholino ring;
R
19Be halogen, C
1-C
2Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
Condition is:
ⅰ) work as G
1, G
2, G
3Or G
4In any one when being O, then they not with O or S(O) the p Direct Bonding;
ⅱ) work as G
1, G
2, G
3Or G
4In any one be S(O) or S(O)
2The time, then they not with C(=O) Direct Bonding;
ⅲ) the heteroatomic sum in containing the ring of A is no more than 2; With
ⅳ) when X, Y and Z be that CH, A are CH
2, Q is the unsubstituted benzene of condensed, R
1And R
2When being H, R then
3It or not unsubstituted phenyl; And
ⅴ) described compound is not 2-[4,6-two (trichloromethyl)-1,3,5-triazines-2-yl]-1,10-phenanthroline or 2-(2-pyridyl)-1, the 10-phenanthroline.
8, a kind of method of preventing and treating the Plant diseases that causes by fungal plant pathogen; it comprises to the plant that will protect or its part; or to the plant seed that will protect or its seedling, formula I A compound or its agricultural of using effective quantity go up salt or the complex compound that is suitable for
Wherein:
X is N or CR
4;
Y is N or CR
5;
Z is N or CR
6;
Q is condensed benzene, naphthalene, thiophene, furans, pyrroles, pyridine or pyrimidine ring, and they can randomly be R separately
7And R
8Replace;
A is an abutment-G
1-G
2-G
3-G
4-, G wherein
1, G
2, G
3Or G
4Be O, S(O independently of one another) p, NR
9, CR
10R
11, C(=O), direct key, perhaps a G
1-G
2, G
2-G
3Or G
3-G
4Can form together-CH=CH-; G
1, G
2, G
3And G
4In at least one be not direct key;
R
1, R
2, R
3And R
4Be H, halogen, cyano group, hydroxyl, C independently of one another
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, randomly use 1-2 methyl substituted C
3-C
6Cycloalkyl, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
4Alkenyl, C
2-C
4Halogenated alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, NR
12R
13, can randomly use R
14The phenyl or the phenoxy group that replace; Perhaps R
1And R
4, R
2And R
4Or R
2And R
5Formation-(CH together
2)
3-,-(CH
2)
4-or a condensed phenyl ring;
R
5And R
6Be H, halogen, C independently of one another
1-C
2Alkyl or C
1-C
2Alkoxyl group;
R
7Be halogen, cyano group, nitro, hydroxyl, hydroxycarbonyl group, C
1-C
6Alkyl, C
1-C
4Haloalkyl, C
1-C
4Alkyl sulfenyl, C
1-C
4Alkyl sulphinyl, C
1-C
4Alkyl sulphonyl, (C
1-C
4Alkyl)
3Silyl, C
3-C
6Cycloalkyl, C
2-C
5Alkyl-carbonyl, C
2-C
4Alkenyl, C
2-C
4Alkenyloxy, C
2-C
4Alkynyl, C
2-C
4Alkynyloxy group, C
1-C
4Alkoxyl group, C
1-C
4Halogenated alkoxy, C
2-C
4Alkoxyalkyl, C
2-C
5Alkoxy carbonyl, C
2-C
4Alkoxyalkoxy group, NR
15R
16, C(=O) NR
17R
18; Or can randomly use R separately
19The phenyl, phenoxy group or the thiophenyl that replace;
R
8And R
14Be 1-2 halogen, 1-2C independently of one another
1-C
3Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
R
9, R
10And R
11Be H or C independently
1-C
2Alkyl;
R
12, R
13, R
15, R
16, R
17And R
18Be H or C independently of one another
1-C
2Alkyl; Perhaps R
12And R
13, R
15And R
16Or R
17And R
18Can form a piperidino-(1-position only) with the nitrogen-atoms that they connected, pyrrolidyl or morpholino ring;
R
19Be halogen, C
1-C
2Alkyl, C
1-C
2Haloalkyl, C
1-C
2Alkoxyl group or C
1-C
2Halogenated alkoxy;
P is 0,1 or 2;
Condition is:
ⅰ) work as G
1, G
2, G
3Or G
4In any one when being O, they not with O or S(O) the direct Cheng Jian of p;
ⅱ) work as G
1, G
2, G
3Or G
4In any one be S(O) or S(O)
2The time, they not with S(O) direct Cheng Jian; With
ⅲ) the heteroatoms sum in containing the ring of A is no more than 2.
9, a kind of method of preventing and treating the Plant diseases that is caused by fungal plant pathogen comprises plant or its part to protecting, or plant seed or seedling to protecting, uses the composition of the claim 7 of effective quantity.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US82172492A | 1992-01-15 | 1992-01-15 | |
| US821,724 | 1992-01-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1074443A true CN1074443A (en) | 1993-07-21 |
Family
ID=25234144
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 93100432 Pending CN1074443A (en) | 1992-01-15 | 1993-01-15 | The heterocyclic fungicides of bridging |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0623125A1 (en) |
| CN (1) | CN1074443A (en) |
| AU (1) | AU3427093A (en) |
| WO (1) | WO1993014080A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102770433A (en) * | 2010-02-24 | 2012-11-07 | 先正达参股股份有限公司 | Novel microbicides |
| CN113793910A (en) * | 2021-10-22 | 2021-12-14 | 浙江华显光电科技有限公司 | Organic optoelectronic device and display or lighting device comprising same |
| CN114258915A (en) * | 2022-02-16 | 2022-04-01 | 云南农业大学 | Application of 9-phenanthrol in rice blast prevention and control |
| CN115023421A (en) * | 2020-02-12 | 2022-09-06 | 优迈特株式会社 | Fluorine-containing pyrimidine compound and method for producing same |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20080145A1 (en) | 2006-03-21 | 2008-02-11 | Janssen Pharmaceutica Nv | TETRAHYDRO-PYRIMIDOAZEPINE AS MODULATORS OF TRPV1 |
| WO2008013622A2 (en) * | 2006-07-27 | 2008-01-31 | E. I. Du Pont De Nemours And Company | Fungicidal azocyclic amides |
| JP5058588B2 (en) | 2006-12-26 | 2012-10-24 | キヤノン株式会社 | Azafluorene derivative and organic light-emitting device using the same |
| JP5562865B2 (en) | 2007-12-17 | 2014-07-30 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | TRPV1 imidazolo-, oxazolo-, and thiazolopyrimidine modulators |
| WO2009081222A1 (en) | 2007-12-21 | 2009-07-02 | Glenmark Pharmaceuticals, S.A. | Substituted tricyclic pyridine or pyrimidine vanilloid receptor ligands |
| KR101840313B1 (en) * | 2011-02-14 | 2018-03-21 | 에스에프씨 주식회사 | Pyridine derivative compound and organic electroluminescent device comprising the same |
| GB2503789A (en) * | 2012-05-15 | 2014-01-08 | Syngenta Participations Ag | Quinazoline derivatives as antifungal agents |
| WO2013180376A1 (en) * | 2012-05-30 | 2013-12-05 | Alpha Chem Co., Ltd. | New electron transport material and organic electroluminescent device using the same |
| EP2738171A1 (en) * | 2012-11-30 | 2014-06-04 | Syngenta Participations AG. | Pesticidally active tricyclic pyridyl derivatives |
| AR095443A1 (en) * | 2013-03-15 | 2015-10-14 | Fundación Centro Nac De Investig Oncológicas Carlos Iii | HEREROCICLES CONDENSED WITH ACTION ON ATR |
| DK3466949T3 (en) * | 2013-12-24 | 2021-03-15 | Bristol Myers Squibb Co | TRICYCLIC COMPOUND AS ANTICANCY AGENTS |
| US9458156B2 (en) | 2014-12-23 | 2016-10-04 | Bristol-Myers Squibb Company | Tricyclic compounds as anticancer agents |
| CN118660882A (en) * | 2022-02-09 | 2024-09-17 | 默克专利有限公司 | Material for organic electroluminescent device |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4189323A (en) * | 1977-04-25 | 1980-02-19 | Hoechst Aktiengesellschaft | Radiation-sensitive copying composition |
| GR75076B (en) * | 1980-10-17 | 1984-07-13 | Ciba Geigy | |
| EP0278610A3 (en) * | 1987-02-13 | 1990-03-14 | Sumitomo Chemical Company, Limited | Novel pyridinyl-s-triazine derivatives, method for production thereof and a fungicide containing them as the active ingredient |
| KR880013917A (en) * | 1987-05-19 | 1988-12-22 | 모리 히데오 | New pyridinylpyrimidine derivatives, preparations thereof and fungicides using the same |
| DE3937284A1 (en) * | 1989-11-09 | 1991-05-16 | Hoechst Ag | PYRIMIDINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF, THE AGENTS CONTAINING THEY AND THEIR USE AS FUNGICIDES |
-
1992
- 1992-12-30 AU AU34270/93A patent/AU3427093A/en not_active Abandoned
- 1992-12-30 WO PCT/US1992/011329 patent/WO1993014080A1/en not_active Application Discontinuation
- 1992-12-30 EP EP93902842A patent/EP0623125A1/en not_active Withdrawn
-
1993
- 1993-01-15 CN CN 93100432 patent/CN1074443A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102770433A (en) * | 2010-02-24 | 2012-11-07 | 先正达参股股份有限公司 | Novel microbicides |
| CN115023421A (en) * | 2020-02-12 | 2022-09-06 | 优迈特株式会社 | Fluorine-containing pyrimidine compound and method for producing same |
| CN115023421B (en) * | 2020-02-12 | 2024-05-24 | 优迈特株式会社 | Fluorine-containing pyrimidine compound and process for producing the same |
| CN113793910A (en) * | 2021-10-22 | 2021-12-14 | 浙江华显光电科技有限公司 | Organic optoelectronic device and display or lighting device comprising same |
| CN114258915A (en) * | 2022-02-16 | 2022-04-01 | 云南农业大学 | Application of 9-phenanthrol in rice blast prevention and control |
Also Published As
| Publication number | Publication date |
|---|---|
| AU3427093A (en) | 1993-08-03 |
| WO1993014080A1 (en) | 1993-07-22 |
| EP0623125A1 (en) | 1994-11-09 |
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