CN106279040B - Pyrimidine compound containing oximino and application thereof - Google Patents

Pyrimidine compound containing oximino and application thereof Download PDF

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Publication number
CN106279040B
CN106279040B CN201510309294.0A CN201510309294A CN106279040B CN 106279040 B CN106279040 B CN 106279040B CN 201510309294 A CN201510309294 A CN 201510309294A CN 106279040 B CN106279040 B CN 106279040B
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acid
compound
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CN106279040A (en
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王立增
关爱莹
范晓溪
孙旭峰
王军锋
杨帆
李轲轲
单中刚
刘长令
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Shenyang Sinochem Agrochemicals R&D Co Ltd
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Shenyang Sinochem Agrochemicals R&D Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • 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
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links

Abstract

The invention belongs to the field of agricultural sterilization, insecticide and acaricide, and particularly relates to a novel pyrimidine compound containing an oxime group and application thereof. The oxime group-containing pyrimidine compound has a structure shown in a general formula I:

Description

Pyrimidine compound containing oximino and application thereof
Technical Field
The invention belongs to the field of agricultural sterilization, insecticide and acaricide, and particularly relates to a novel pyrimidine compound containing an oxime group and application thereof.
Background
Patent CN103058935A reports that the following compound formula and specific compound have inhibitory effect on tumor cells and viruses.
Figure BDA0000733339380000011
The pyrimidine compound containing oximino, the structure of which is shown in the general formula I, is not reported.
Disclosure of Invention
The invention aims to provide a pyrimidine compound containing oximino, which can control various germs, pests and mites and can be used for preparing medicines for preventing and controlling germs, pests and mites in agriculture or other fields.
The technical scheme of the invention is as follows:
the invention provides a pyrimidine compound containing oximino, which is shown as a general formula I:
Figure BDA0000733339380000012
in the formula:
R1selected from hydrogen, halogen, C1-C12Alkyl radical, C3-C12Cycloalkyl, halo C1-C12Alkyl radical, C2-C12Alkenyl, halo C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkynyl, C1-C12Alkoxy radical C1-C12Alkyl or halo C1-C12Alkoxy radical C1-C12An alkyl group;
R2selected from hydroxy, amino, cyano, C1-C12Alkoxy radical, C3-C12Cycloalkoxy, halo C1-C12Alkoxy radical, C2-C12Alkenyloxy, halogeno C2-C12Alkenyloxy radical, C2-C12Alkynyloxy, halo C2-C12Alkynyloxy, C1-C12Alkylamino radical, C3-C12Cycloalkylamino, halo C1-C12Alkylamino radical, C1-C12Alkoxy radical C1-C12Alkoxy, halo C1-C12Alkoxy radical C1-C12Alkoxy radical, C1-C12Alkoxy radical C1-C12Alkylamino or halogeno C1-C12Alkoxy radical C1-C12An alkylamino group;
R3selected from hydrogen, halogen, C1-C12Alkyl radical, C1-C12Alkoxy radical, C1-C12Alkylthio or C1-C12An alkylsulfonyl group;
b is selected from-CH2-，-CH2CH2-，-CH2CH2CH2-，-CHR4-，-CR4R5-，-CHR4CH2-，-CR4R5CH2-，-CH2CR4R5-，-CHR4CHR5-，-CR4R5CHR5-，-CHR4CR4R5-or-CR4R5CR4R5-；
R4、R5May be the same or different and are selected from C1-C12Alkyl radical, C3-C12Cycloalkyl radical, C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkenyl, halo C2-C12Alkynyl, C1-C12Alkoxy radical C1-C12Alkyl, aryl C unsubstituted or further substituted by 1 to 51-C6Alkyl or heteroaryl C1-C6Alkyl groups: halogen, C1-C6Alkyl, halo C1-C6Alkyl radical, C1-C6Alkoxy or halo C1-C6An alkoxy group; or R4、R5With carbon bound to form C3-C8A ring of (a);
X1、X2、X3、X4can be the same or different and are respectively selected from hydrogen, halogen, nitro, cyano and C1-C12Alkyl, halo C1-C12Alkyl radical, C3-C12Cycloalkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C1-C12Alkylthio, halo C1-C12Alkylthio radical, C2-C12Alkenyl, halo C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkynyl, C3-C12Alkenyloxy, halogeno C3-C12Alkenyloxy radical, C3-C12Alkynyloxy, halo C3-C12Alkynyloxy, C1-C12Alkylsulfinyl, halogeno C1-C12Alkylsulfinyl radical, C1-C12Alkylsulfonyl, halo C1-C12Alkylsulfonyl radical, C1-C12Alkylcarbonyl, halo C1-C12Alkylcarbonyl group, C1-C12Alkylcarbonyloxy, C1-C12Alkylcarbonylamino, C1-C12Alkylsulfonyloxy, C1-C12Alkoxycarbonyl group, C1-C12Alkoxycarbonyl radical C1-C12Alkyl radical, C1-C12Alkoxycarbonylamino group, C1-C12Alkoxy radical C1-C12Alkoxy or C1-C12Alkoxycarbonyl radical C1-C12An alkoxy group;
R6selected from hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy radical,Halogen substituted C1-C12Alkoxy radical, C3-C12Cycloalkyl radical, C2-C12Alkenyl radical, C2-C12Alkynyl, C2-C12Alkenyloxy, halogeno C2-C12Alkenyloxy radical, C2-C12Alkynyloxy, halo C2-C12Alkynyloxy, C1-C12Alkylthio, halo C1-C12Alkylthio radical, C1-C12Alkoxy radical C1-C12Alkyl, halo C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylthio group C1-C12Alkyl, halo C1-C12Alkylthio group C1-C12Alkyl radical, C1-C12Alkylsulfinyl, halogeno C1-C12Alkylsulfinyl radical, C1-C12Alkylsulfonyl, halo C1-C12Alkylsulfonyl radical, C1-C12Alkylaminosulfonyl radical, C1-C12Alkylamino, halogeno C1-C12Alkylamino radical, di (C)1-C12Alkyl) amino, C1-C12Alkoxycarbonyl, di (C)1-C12Alkyl) amino (C)1-C12Alkyl), halo C1-C12Alkoxycarbonyl, CONH2、CONHNH2、CON(C1-C12Alkyl) NH2、CONHNH(C1-C12Alkyl), CONHN (di (C)1-C12Alkyl)), CONHNHCO (C)1-C12Alkyl), CONHNHCO2(C1-C12Alkyl), CONHNH (phenyl), C1-C12Alkylaminocarbonyl, di (C)1-C12Alkyl) aminocarbonyl, C1-C12Alkylsulfonylamino group, C1-C12Alkylsulfonyl (C)1-C12Alkyl) amino, halo C1-C12Alkylsulfonylamino group, C1-C12Alkoxyamino group, C1-C12Alkoxycarbonylamino group, C1-C12Alkoxy radicalAminocarbonyl, cyano C1-C12Alkyl, cyano C1-C12Alkoxy radical, C1-C12Alkoxycarbonyl radical C1-C12Alkyl radical, C1-C12Alkylaminocarbonyl radical C1-C12Alkyl or di (C)1-C12Alkyl) aminocarbonyl group C1-C12An alkyl group;
q is selected from N or CR7W is selected from N or CR8Y is selected from N or CR9Z is selected from N or CR10(ii) a Q, W, Y, Z is not N at the same time;
R7、R8、R9、R10can be the same or different and are respectively selected from hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro and C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C1-C12Alkoxycarbonyl, CONH2、C1-C12Alkylaminocarbonyl or di (C)1-C12Alkyl) aminocarbonyl;
a is selected from O, S or NR11；
R11Selected from hydrogen, hydroxy, formyl, C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C3-C12Cycloalkyl radical, C1-C12Alkylthio radical, C2-C12Alkenylthio radical, C2-C12Alkenyl radical, C2-C12Alkynyl, halo C2-C12Alkenyl, halo C2-C12Alkynyl, C1-C12Alkoxy radical C1-C12Alkyl, halo C1-C12Alkoxy radical C1-C12Alkyl radical, C1-C12Alkylthio group C1-C12Alkyl, halo C1-C12Alkylthio group C1-C12Alkyl radical, C1-C12Alkylsulfinyl, halogeno C1-C12Alkylsulfinyl radical, C1-C12Alkylsulfonyl, halo C1-C12Alkylsulfonyl radical, C1-C12Alkylaminosulfonyl, di (C)1-C12Alkyl) aminosulfonyl, C1-C12Alkylsulfonylaminocarbonyl group, C1-C12Alkylcarbonylaminosulfonyl radical, C3-C12Cycloalkyloxycarbonyl radical, C1-C12Alkylcarbonyl, halo C1-C12Alkylcarbonyl group, C1-C12Alkoxycarbonyl, halo C1-C12Alkoxycarbonyl group, C1-C12Alkyl carbonyl radical C1-C12Alkyl radical, C1-C12Alkoxycarbonyl radical C1-C12Alkyl radical, C1-C12Alkylaminocarbonyl, di (C)1-C12Alkyl) aminocarbonyl, C2-C12Alkenyloxycarbonyl radical, C2-C12Alkynyloxycarbonyl group, C1-C12Alkoxy radical C1-C12Alkoxycarbonyl group, C1-C12Alkylaminosulfenyl, di (C)1-C12Alkyl) aminosulfanyl, (hetero) arylcarbonyl C which is unsubstituted or further substituted by 1 to 51-C6Alkyl, (hetero) arylcarbonyl, (hetero) aryloxycarbonyl, (hetero) aryl C1-C6Alkyloxycarbonyl or (hetero) aryl C1-C6Alkyl groups: halogen, nitro, cyano, C1-C6Alkyl, halo C1-C6Alkyl radical, C1-C6Alkoxy or halo C1-C6An alkoxy group;
or a salt of a compound of formula I.
Preferred compounds of the invention are: in the general formula I
R1Selected from hydrogen, halogen, C1-C8Alkyl radical, C3-C8Cycloalkyl, halo C1-C8Alkyl radical, C2-C8Alkenyl, halo C2-C8Alkenyl radical, C2-C8Alkynyl, halo C2-C8Alkynyl, C1-C8Alkoxy radical C1-C8Alkyl or halo C1-C8Alkoxy radical C1-C8An alkyl group;
R2selected from hydroxy, amino, cyano, C1-C8Alkoxy radical, C3-C8Cycloalkoxy, halo C1-C8Alkoxy radical, C2-C8Alkenyloxy, halogeno C2-C8Alkenyloxy radical, C2-C8Alkynyloxy, halo C2-C8Alkynyloxy, C1-C8Alkylamino radical, C3-C8Cycloalkylamino, halo C1-C8Alkylamino radical, C1-C8Alkoxy radical C1-C8Alkoxy, halo C1-C8Alkoxy radical C1-C8Alkoxy radical, C1-C8Alkoxy radical C1-C8Alkylamino or halogeno C1-C8Alkoxy radical C1-C8An alkylamino group;
R3selected from hydrogen, halogen, C1-C8Alkyl radical, C1-C8Alkoxy radical, C1-C8Alkylthio or C1-C8An alkylsulfonyl group;
b is selected from-CH2-，-CH2CH2-，-CH2CH2CH2-，-CHR4-，-CR4R5-，-CHR4CH2-，-CR4R5CH2-，-CH2CR4R5-，-CHR4CHR5-，-CR4R5CHR5-，-CHR4CR4R5-or-CR4R5CR4R5-；
R4、R5May be the same or different and are selected from C1-C8Alkyl radical, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, halo C2-C8Alkenyl, halo C2-C8Alkynyl, C1-C8Alkoxy radical C1-C8Alkyl, aryl C unsubstituted or further substituted by 1 to 31-C4Alkyl or heteroaryl C1-C4Alkyl groups: halogen, C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy or halo C1-C4An alkoxy group; or R4、R5With carbon bound to form C3-C8A ring of (a);
X1、X2、X3、X4can be the same or different and are respectively selected from hydrogen, halogen, nitro, cyano and C1-C8Alkyl, halo C1-C8Alkyl radical, C3-C8Cycloalkyl radical, C1-C8Alkoxy, halo C1-C8Alkoxy radical, C1-C8Alkylthio, halo C1-C8Alkylthio radical, C2-C8Alkenyl, halo C2-C8Alkenyl radical, C2-C8Alkynyl, halo C2-C8Alkynyl, C3-C8Alkenyloxy, halogeno C3-C8Alkenyloxy radical, C3-C8Alkynyloxy, halo C3-C8Alkynyloxy, C1-C8Alkylsulfinyl, halogeno C1-C8Alkylsulfinyl radical, C1-C8Alkylsulfonyl, halo C1-C8Alkylsulfonyl radical, C1-C8Alkylcarbonyl, halo C1-C8Alkylcarbonyl group, C1-C8Alkylcarbonyloxy, C1-C8Alkylcarbonylamino, C1-C8Alkylsulfonyloxy, C1-C8Alkoxycarbonyl group, C1-C8Alkoxycarbonyl radical C1-C8Alkyl radical, C1-C8Alkoxycarbonylamino group, C1-C8Alkoxy radical C1-C8Alkoxy or C1-C8Alkoxycarbonyl radical C1-C8An alkoxy group;
R6selected from hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C1-C8Alkyl, halo C1-C8Alkyl radical, C1-C8Alkoxy, halo C1-C8Alkoxy radical, C3-C8Cycloalkyl radical, C2-C8Alkenyl radical, C2-C8Alkynyl, C2-C8Alkenyloxy, halogeno C2-C8Alkenyloxy radical, C2-C8Alkynyloxy, halo C2-C8Alkynyloxy, C1-C8Alkylthio, halo C1-C8Alkylthio radical, C1-C8Alkoxy radical C1-C8Alkyl, halo C1-C8Alkoxy radical C1-C8Alkyl radical, C1-C8Alkylthio group C1-C8Alkyl, halo C1-C8Alkylthio group C1-C8Alkyl radical, C1-C8Alkylsulfinyl, halogeno C1-C8Alkylsulfinyl radical, C1-C8Alkylsulfonyl, halo C1-C8Alkylsulfonyl radical, C1-C8Alkylaminosulfonyl radical, C1-C8Alkylamino, halogeno C1-C8Alkylamino radical, di (C)1-C8Alkyl) amino, C1-C8Alkoxycarbonyl, di (C)1-C8Alkyl) amino (C)1-C8Alkyl), halo C1-C8Alkoxycarbonyl, CONH2、CONHNH2、CON(C1-C8Alkyl) NH2、CONHNH(C1-C8Alkyl), CONHN (di (C)1-C8Alkyl)), CONHNHCO (C)1-C8Alkyl), CONHNHCO2(C1-C8Alkyl), CONHNH (phenyl), C1-C8Alkylaminocarbonyl, di (C)1-C8Alkyl) aminocarbonyl, C1-C8Alkylsulfonylamino group, C1-C8Alkylsulfonyl (C)1-C8Alkyl) amino, halo C1-C8Alkylsulfonylamino group, C1-C8Alkoxyamino group, C1-C8Alkoxycarbonylamino group, C1-C8Alkoxyaminocarbonyl, cyano C1-C8Alkyl, cyano C1-C8Alkoxy radical, C1-C8Alkoxycarbonyl radical C1-C8Alkyl radical, C1-C8Alkylaminocarbonyl radical C1-C8Alkyl or di (C)1-C8Alkyl) aminocarbonyl group C1-C8An alkyl group;
q is selected from N or CR7W is selected from N or CR8Y is selected from N or CR9Z is selected from N or CR10(ii) a Q, W, Y, Z is not N at the same time;
R7、R8、R9、R10can be the same or different and are respectively selected from hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro and C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C1-C12Alkoxycarbonyl, CONH2、C1-C12Alkylaminocarbonyl or di (C)1-C12Alkyl) aminocarbonyl;
a is selected from O, S or NR11；
R11Selected from hydrogen, hydroxy, formyl, C1-C8Alkyl, halo C1-C8Alkyl radical, C1-C8Alkoxy, halo C1-C8Alkoxy radical, C3-C8Cycloalkyl radical, C1-C8Alkylthio radical, C2-C8Alkenylthio radical, C2-C8Alkenyl radical, C2-C8Alkynyl, halo C2-C8Alkenyl, halo C2-C8Alkynyl, C1-C8Alkoxy radical C1-C8Alkyl, halo C1-C8Alkoxy radical C1-C8Alkyl radical, C1-C8Alkylthio group C1-C8Alkyl, halo C1-C8Alkylthio group C1-C8Alkyl radical, C1-C8Alkylsulfinyl, halogeno C1-C8Alkylsulfinyl radical, C1-C8Alkylsulfonyl, halo C1-C8Alkylsulfonyl radical, C1-C8Alkylaminosulfonyl, di (C)1-C8Alkyl) aminosulfonyl, C1-C8Alkylsulfonylaminocarbonyl group, C1-C8Alkylcarbonylaminosulfonyl radical, C3-C8Cycloalkyloxycarbonyl radical, C1-C8Alkylcarbonyl, halo C1-C8Alkylcarbonyl group, C1-C8Alkoxycarbonyl, halo C1-C8Alkoxycarbonyl group, C1-C8Alkyl carbonyl radical C1-C8Alkyl radical, C1-C8Alkoxycarbonyl radical C1-C8Alkyl radical, C1-C8Alkylaminocarbonyl, di (C)1-C8Alkyl) aminocarbonyl, C2-C8Alkenyloxycarbonyl radical, C2-C8Alkynyloxycarbonyl group, C1-C8Alkoxy radical C1-C8Alkoxycarbonyl group, C1-C12Alkylaminosulfenyl, di (C)1-C8Alkyl) aminosulfanyl, (hetero) arylcarbonyl C which is unsubstituted or further substituted by 1 to 31-C6Alkyl, (hetero) arylcarbonyl, (hetero) aryloxycarbonyl, (hetero) aryl C1-C6Alkyloxycarbonyl or (hetero) aryl C1-C6Alkyl groups: halogen, nitro, cyano, C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy or halo C1-C4An alkoxy group;
or a salt of a compound of formula I.
Further preferred compounds of the invention are: in the general formula I
R1Selected from hydrogen, halogen, C1-C4Alkyl radical, C3-C6Cycloalkyl, halo C1-C4Alkyl radical, C2-C4Alkenyl, halo C2-C4Alkenyl radical, C2-C4Alkynyl, halo C2-C4Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl or halo C1-C4Alkoxy radical C1-C4An alkyl group;
R2selected from hydroxy, amino, cyano, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C1-C4Alkylamino or halogeno C1-C4An alkylamino group;
R3selected from hydrogen, halogen or methyl;
b is selected from-CH2-，-CH2CH2-，-CH2CH2CH2-，-CHR4-，-CR4R5-，-CHR4CH2-，-CR4R5CH2-，-CH2CR4R5-；
R4、R5Selected from methyl or ethyl;
X1、X2、X3、X4can be the same or different and are respectively selected from hydrogen, halogen, nitro, cyano and C1-C4Alkyl, halo C1-C4Alkyl radical, C3-C4Cycloalkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C1-C4Alkylthio, halo C1-C4Alkylthio radical, C2-C4Alkenyl radical, C2-C4Alkynyl, C1-C4Alkylsulfinyl radical, C1-C4Alkylsulfonyl radical, C1-C4Alkylcarbonyl or C1-C4Alkoxy radical C1-C4An alkoxy group;
R6selected from hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C1-C8Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C3-C4Cycloalkyl radical, C2-C4Alkenyl radical, C2-C4Alkynyl, C2-C4Alkenyloxy, halogeno C2-C4Alkenyloxy radical, C2-C4Alkynyloxy, halo C2-C4Alkynyloxy, C1-C4Alkylthio, halo C1-C4Alkylthio radical, C1-C4Alkoxy radical C1-C4Alkyl, halo C1-C4Alkoxy radical C1-C4Alkyl radical, C1-C4Alkylthio group C1-C4Alkyl, halo C1-C4Alkylthio group C1-C4Alkyl radical, C1-C4Alkylsulfinyl, halogeno C1-C4Alkylsulfinyl radical, C1-C4Alkylsulfonyl, halo C1-C4Alkylsulfonyl radical, C1-C4Alkylaminosulfonyl radical, C1-C4Alkylamino, halogeno C1-C4Alkylamino radical, di (C)1-C4Alkyl) amino, C1-C4Alkoxycarbonyl, di (C)1-C4Alkyl) amino (C)1-C4Alkyl), halo C1-C4Alkoxycarbonyl, CONH2、CONHNH2、CON(C1-C4Alkyl) NH2、CONHNH(C1-C4Alkyl), CONHN (di (C)1-C4Alkyl)), CONHNHCO (C)1-C4Alkyl), CONHNHCO2(C1-C4Alkyl), CONHNH (phenyl), C1-C4Alkylaminocarbonyl, di (C)1-C4Alkyl) aminocarbonyl, C1-C4Alkylsulfonylamino group, C1-C4Alkylsulfonyl (C)1-C4Alkyl) amino, halo C1-C4Alkylsulfonylamino group, C1-C4Alkoxyamino group, C1-C4Alkoxycarbonylamino group, C1-C4Alkoxyaminocarbonyl, cyano C1-C4Alkyl, cyano C1-C4Alkoxy radical, C1-C4Alkoxycarbonyl radical C1-C4Alkyl radical, C1-C4Alkylaminocarbonyl radical C1-C4Alkyl or di (C)1-C4Alkyl) aminocarbonyl group C1-C4An alkyl group;
q is selected from N or CR7W is selected from N or CR8Y is selected from N or CR9Z is selected from N or CR10(ii) a Q, W, Y, Z is not N at the same time;
R7、R8、R9、R10can be the same or different and are respectively selected from hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro and C1-C12Alkyl, halo C1-C12Alkyl radical, C1-C12Alkoxy, halo C1-C12Alkoxy radical, C1-C12Alkoxycarbonyl, CONH2、C1-C12Alkylaminocarbonyl or di (C)1-C12Alkyl) aminocarbonyl;
a is selected from O, S or NH;
or salts of the compounds of the general formula I with hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, sorbic acid, malic acid or citric acid.
Further preferred compounds of the invention are: I-A, I-a, I-B, I-b, I-C, I-c, I-D, I-d, I-E, I-e, I-F, I-f, I-G, I-g, I-H, I-h, I-I, I-I, I-J, I-j, I-K, I-k, I-L, I-l, I-M, I-m, I-N, I-n, I-O, I-o, I-P, I-p, I-Q, I-q, I-R, I-r, I-S, I-s, I-T or I-T
Figure BDA0000733339380000051
Figure BDA0000733339380000061
Figure BDA0000733339380000071
R1Selected from hydrogen, halogen, C1-C4Alkyl radical, C3-C6Cycloalkyl, halo C1-C4Alkyl radical, C2-C4Alkenyl radical, C2-C4Alkynyl, C1-C4Alkoxy radical C1-C4Alkyl or halo C1-C4Alkoxy radical C1-C4An alkyl group;
R2selected from hydroxy, amino, cyano, C1-C4Alkoxy, halo C1-C4Alkoxy radical, C1-C4Alkylamino or halogeno C1-C4An alkylamino group;
R3selected from hydrogen or methyl;
R4、R5selected from methyl or ethyl;
X1、X2、X3、X4can be the same or different and are respectively selected from hydrogen, halogen, nitro, cyano and C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy, halo C1-C4Alkoxy or C1-C4An alkylcarbonyl group;
R6selected from hydrogen, halogen, cyano, amino, nitro, C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy or halo C1-C4An alkoxy group;
R7、R8、R9、R10can be the same or different and are respectively selected from hydrogen, halogen, cyano, amino, nitro and C1-C4Alkyl, halo C1-C4Alkyl radical, C1-C4Alkoxy or halo C1-C4An alkoxy group;
a is selected from O, S or NH;
or the general formula I-A, I-a, I-B, I-b, I-C, I-c, I-D, I-d, I-E, I-e, I-F, I-f, I-G, I-g, I-H, I-h, I-I, I-I, I-J, I-j, I-K, I-k, I-L, I-l, I-M, I-m, I-N, I-n, I-O, I-o, I-P, I-p, I-Q, I-q, I-R, I-r, I-S, I-s, I-T or I-T and hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, Acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, sorbic acid, malic acid or citric acid.
Still further preferred compounds of the invention are:
in the general formula I-A
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, amino, cyano, methoxy, ethoxy, methylamino or ethylamino;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R8、R9、R10selected from hydrogen, halogen, cyano, methyl, trifluoromethyl, methoxy or trifluoromethoxy;
a is selected from NH;
or, in the general formula I-B
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, amino, cyano, methoxy, ethoxy, methylamino or ethylamino;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R9、R10selected from hydrogen, halogen, cyano, methyl, trifluoromethyl, methoxy or trifluoromethoxy;
a is selected from NH;
or, in the general formula I-F
R1Selected from chlorineMethyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, amino, cyano, methoxy, ethoxy, methylamino or ethylamino;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R10selected from hydrogen, halogen, methyl, trifluoromethyl, methoxy or trifluoromethoxy;
a is selected from NH;
or, in the general formula I-K
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, amino, cyano, methoxy, ethoxy, methylamino or ethylamino;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R8、R9、R10selected from hydrogen, halogen, cyano, methyl, trifluoromethyl, methoxy or trifluoromethoxy;
a is selected from NH;
or, in the general formula I-L
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, amino, cyano, methoxy, ethoxy, methylamino, ethylamino;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R9、R10selected from hydrogen, halogen, cyano, methyl, trifluoromethyl, methoxy or trifluoromethoxy;
a is selected from NH;
alternatively, the compounds of formula I-A, I-B, I-F, I-K or I-L are salts with hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, sorbic acid, malic acid or citric acid.
Still further preferred compounds of the invention are:
in the general formula I-A
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R8、R9、R10selected from hydrogen, halogen, cyano, methyl, trifluoromethyl, methoxy or trifluoromethoxy;
a is selected from NH;
or, in the general formula I-B
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R9、R10selected from hydrogen, halogen or trifluoromethyl;
a is selected from NH;
or, in the general formula I-F
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R10selected from hydrogen, halogen or methyl;
a is selected from NH;
or, in the general formula I-K
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R8、R9、R10selected from hydrogen, halogen, cyano, methyl, trifluoromethyl, methoxy or trifluoromethoxy;
a is selected from NH;
or, in the general formula I-L
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or halogen;
R6、R7、R9、R10selected from hydrogen, halogen or trifluoromethyl;
a is selected from NH;
alternatively, the compounds of formula I-A, I-B, I-F, I-K or I-L are salts with hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, sorbic acid, malic acid or citric acid.
The most preferred compounds of the invention are:
in the general formula I-A
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or chlorine;
R6、R7、R8、R9、R10selected from hydrogen, fluoro, chloro, cyano, methyl or trifluoromethyl;
a is selected from NH;
or, in the general formula I-B
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen or chlorine; (ii) a
R6、R7、R9、R10Selected from hydrogen, chloro or trifluoromethyl;
a is selected from NH;
or, in the general formula I-F
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen or methyl;
X1、X2、X3、X4selected from hydrogen;
R6、R7、R10selected from hydrogen, chlorine or methyl;
a is selected from NH;
or, in the general formula I-L
R1Selected from chlorine, methyl, ethyl, CHF2Or trifluoromethyl;
R2selected from hydroxy and methoxyAn alkyl group or an ethoxy group;
R3selected from hydrogen or methyl;
X1、X2、X3、X4selected from hydrogen;
R6、R7、R9、R10selected from hydrogen, halogen or trifluoromethyl;
a is selected from NH;
alternatively, the compounds of formula I-A, I-B, I-F or I-L form salts with hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, sorbic acid, malic acid or citric acid.
In the definitions of the compounds of the general formula I given above, the terms used are generally defined as follows: halogen: refers to fluorine, chlorine, bromine or iodine. Alkyl groups: straight-chain or branched alkyl radicals, such as methyl, ethyl, propyl, isopropyl, n-butyl-tert-butyl or butyl. Cycloalkyl groups: substituted or unsubstituted cyclic alkyl groups, such as cyclopropyl, cyclopentyl or cyclohexyl. Substituents such as methyl, halogen, and the like. Halogenated alkyl groups: straight-chain or branched alkyl groups in which the hydrogen atoms may be partially or completely substituted with halogen atoms, for example, chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl and the like. Alkoxy groups: straight or branched chain alkyl groups attached to the structure via oxygen atom linkages. Haloalkoxy groups: straight-chain or branched alkoxy groups in which the hydrogen atoms may be partially or completely replaced by halogen atoms. For example, chloromethoxy, dichloromethoxy, trichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, chlorofluoromethoxy, trifluoroethoxy and the like. Alkylthio group: straight or branched chain alkyl groups attached to the structure via a sulfur atom. Haloalkylthio: straight-chain or branched alkylthio groups in which the hydrogen atoms may be partially or wholly replaced by halogen atoms. For example, chloromethylthio, dichloromethylthio, trichloromethylthio, fluoromethylthio, difluoromethylthio, trifluoromethylthio, chlorofluoromethylthio and the like. Cyanoalkyl group: straight-chain or branched alkyl radicals in which the hydrogen atoms may be partly substituted by cyano radicals, e.g. CNCH2-、CNCH2CH2-、CCN(CH3)2CH2-、(CN)2CHCH2-and the like. Cyanoalkoxy group: the cyanoalkyl group is attached to the structure via an oxygen atom bond. Such as CNCH2O-is formed. Alkylamino group: straight or branched chain alkyl, linked to the structure via a nitrogen atom. Haloalkylamino group: straight-chain or branched alkylamino groups in which the hydrogen atoms may be partially or fully substituted by halogen atoms. Dialkylamino group: such as (CH)3)2N-，(CH3CH2)2N-is provided. Dialkylaminoalkyl: such as (CH)3)2NCH2-. Alkenyl: straight-chain or branched alkenes, for example ethenyl, 1-propenyl, 2-propenyl and the different butenyl, pentenyl and hexenyl isomers. Alkenyl also includes polyenes such as 1, 2-allenyl and 2, 4-hexadienyl. Halogenated alkenyl groups: straight-chain or branched alkenes in which the hydrogen atoms may be partially or completely replaced by halogen atoms. Alkynyl: straight-chain or branched alkynes, for example ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. Alkynyl also includes groups consisting of multiple triple bonds, such as 2, 5-hexadiynyl. Halogenated alkynyl group: straight-chain or branched alkynes, in which the hydrogen atoms may be partially or completely replaced by halogen atoms. Alkenyloxy: linear or branched alkenes linked to the structure via oxygen atoms. Haloalkenyloxy: straight-chain or branched alkenyloxy groups in which the hydrogen atoms may be partially or completely replaced by halogen atoms. Alkynyloxy: straight or branched alkynes, linked to the structure via oxygen atom bonds. Haloalkynyloxy: straight-chain or branched alkynyloxy, in which the hydrogen atoms may be partially or completely substituted by halogen atoms. Alkylsulfinyl group: straight or branched chain alkyl groups are attached to the structure via a sulfinyl (-SO-) group, such as methylsulfinyl. Haloalkylsulfinyl group: straight-chain or branched alkylsulfinyl groups in which the hydrogen atoms of the alkyl group may be partially or fully substituted by halogen atoms. An alkylsulfonyl group: straight or branched chain alkyl via sulfonyl (-SO)2-) is attached to a structure, such as a methylsulfonyl group. Haloalkylsulfonyl group: straight-chain or branched alkylsulfonyl wherein the hydrogen atoms of the alkyl group may be partially or wholly substituted by halogen atoms.An alkylcarbonyl group: the alkyl radical being bound to the structure via a carbonyl group, e.g. CH3CO-，CH3CH2CO-. Halogenated alkylcarbonyl group: the hydrogen atoms of the alkyl group of the alkylcarbonyl group may be partially or fully substituted by halogen atoms, e.g. CF3CO-. Alkoxyalkyl groups: alkyl-O-alkyl-, e.g. CH3OCH2-. Haloalkoxyalkyl groups: the hydrogen atoms on the alkyl group of the alkoxyalkyl group may be partially or fully substituted with halogen atoms. Such as ClCH2CH2OCH2-. Alkylthioalkyl: alkyl-S-alkyl-, e.g. CH3SCH2-. Haloalkylthioalkyl: the hydrogen atoms of the alkyl group of an alkylthioalkyl group may be partially or fully substituted by halogen atoms, e.g. ClCH2CH2SCH2-、CF3CH2SCH2-and the like. Alkoxycarbonyl group: the alkoxy group is attached to the structure via a carbonyl group. Such as CH3OCO-，CH3CH2OCO-. Halogenated alkoxycarbonyl group: straight-chain or branched alkoxycarbonyl groups in which the hydrogen atoms may be partially or completely replaced by halogen atoms. Alkyl amino carbonyl: such as CH3NHCO-，CH3CH2NHCO-. Dialkylaminocarbonyl group: such as (CH)3)2NCO-，(CH3CH2)2NCO-. Alkoxycarbonylalkyl groups: such as CH3OCOCH2-，CH3CH2OCOCH2-. Alkoxycarbonylamino group: such as CH3OCONH-，CH3CH2OCONH-. An alkoxyaminocarbonyl group: such as CH3ONHCO-，CH3CH2ONHCO-. Alkylaminocarbonylalkyl: such as CH3NHCOCH2-，CH3CH2NHCOCH2-. Dialkylaminocarbonylalkyl: such as (CH)3)2NCOCH2-，(CH3CH2)2NCOCH2-. Alkenylthio group: linear or branched alkenes linked to the structure via a sulfur atom bond. Such as CH2＝CHCH2S-. Cycloalkyloxy group: a substituted or unsubstituted cyclic alkyl group attached to the structure via an oxygen atom. Cycloalkylamino group: a substituted or unsubstituted cyclic alkyl group attached to the structure via a nitrogen atom. Cycloalkyl oxycarbonyl radical: such as cyclopropyloxycarbonyl, cyclohexyloxycarbonyl, and the like. Alkenyloxycarbonyl radical: such as CH2＝CHCH2OCO-, etc. Alkoxyamino group: such as CH3O NH-. Alkynyloxycarbonyl group: such as CH ≡ CCH2OCO-, etc. Alkoxy alkoxycarbonyl group: such as CH3OCH2CH2OCO-, etc. Alkylaminosulfenyl: such as CH3NHS-、C2H5NHS-. Dialkylaminosulfenyl: such as (CH)3)2NS-、(C2H5)2NS-. Alkylcarbonylalkyl group: alkyl-CO-alkyl-. Alkylsulfonylamino group: alkyl-SO2-NH-. Haloalkylsulfonylamino group: straight-chain or branched alkylsulfonylamino groups, the hydrogen atoms on these alkyl groups may be partially or wholly substituted by halogen atoms. Alkylsulfonylalkylamino group: alkyl-SO2-alkyl-NH-. Alkylaminosulfonyl: alkyl-NH-SO2-. Alkylsulfonylaminocarbonyl group: alkyl-SO2-NH-CO-. Alkylcarbonylamino group: alkyl-CO-NH-. Alkylcarbonylaminosulfonyl: alkyl-CO-NH-SO2-. Dialkylaminosulfonyl: (alkyl group)2-N-SO2-. Alkylcarbonyloxy group: alkyl-CO-O-. Alkylsulfonyloxy group: alkyl-SO2-O-. Alkoxyalkyl amino group: such as CH3O-CH2-NH-. Haloalkoxyalkylamino: CF (compact flash)3O-CH2-NH-. Alkoxyalkoxy group: such as CH3OCH3O-is formed. Haloalkoxyalkyl: such as CF3OCH3O-is formed. Alkoxycarbonylalkoxy group: such as CH3O-CO-CH3And O. The aryl moiety in (hetero) arylcarbonylalkyl, (hetero) arylcarbonyl, (hetero) aryloxycarbonyl, (hetero) arylalkyloxycarbonyl, (hetero) arylalkyl includes phenyl or naphthyl and the like. Heteroaryl is a five or six membered ring containing 1 or more heteroatoms N, O, S. Such as furyl, pyrazolyl, thiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, and the like. (hetero) arylcarbonylalkyl: such as PhCOCH2-. (hetero) aryloxycarbonyl group: such as phenoxycarbonyl, 4-chlorophenoxycarbonyl, 4-nitrophenoxycarbonyl, naphthyloxycarbonyl, etc. Arylalkyloxycarbonyl group: such as benzyloxycarbonyl, 4-chlorobenzyloxyCarbonyl, 4-trifluoromethylbenzyloxycarbonyl, and the like. (hetero) arylcarbonyl group: such as benzoyl, 4-chlorobenzoyl and the like. (hetero) arylalkyloxycarbonyl: such as PhCH2OCO-、4-Cl-PhCH2OCO-, etc. (hetero) arylalkyl: such as benzyl, phenethyl, p-chlorobenzyl, 2-chloro-5-pyridylethyl, 2-chloro-5-thiazolylethyl, and the like.
Tables 1 to 4 respectively list R in the general formula I1、R2、R3、R4、R5Some of the substituents in (1) are specific, but they are not limited to these substituents, and other substituents in formula I are as described above.
Figure BDA0000733339380000121
TABLE 1R1Substituent group
Figure BDA0000733339380000122
TABLE 2R2Substituent group
R2 R2 R2 R2
NH2 NHC4H9-n OH OC4H9-i
CN NHC4H9-i OCH3 OC4H9-t
NHCH3 NHC4H9-t OC2H5 OCH2F
NHC2H5 NHCH2OCH3 OC3H7-n OCHF2
NHC3H7-n OCH2OCH3 OC3H7-i OCF3
NHC3H7-i OCH2OCH2CH3 OC4H9-n OCH2CF3
TABLE 3R3Substituent group
Figure BDA0000733339380000131
TABLE 4R4(R5) Substituent group
Figure BDA0000733339380000132
Some of the compounds of the present invention are illustrated by the specific compounds listed in tables 5-351, but are not intended to limit the present invention. The general formula compounds related in the table are I-A, I-B, I-C, I-D, I-E, I-F, I-G, I-H, I-I, I-K, I-L, I-a, I-b, I-c, I-d, I-e, I-f, I-g, I-h, I-I, I-k or I-l, X is1＝X4＝H。
In the general formula I-A, the compound is shown in the specification,
Figure BDA0000733339380000141
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10For different substituents, see table 5, representing compounds numbered 1-180.
TABLE 5
Numbering R6 R7 R8 R9 R10
1 H H H H H
2 H H F H H
3 H F H H H
4 H H H F H
5 H H Cl H H
6 H Cl H H H
7 H H H Cl H
8 H H Br H H
9 H Br H H H
10 H H H Br H
11 H H I H H
12 H I H H H
13 H H H I H
14 H H CH3 H H
15 H CH3 H H H
16 H H H CH3 H
17 H H OCH3 H H
18 H OCH3 H H H
19 H H H OCH3 H
20 H H CF3 H H
21 H CF3 H H H
22 H H H CF3 H
23 H H OCF3 H H
24 H OCF3 H H H
25 H H H OCF3 H
26 H H NO2 H H
27 H NO2 H H H
28 H H H NO2 H
29 H H CN H H
30 H CN H H H
31 H H H CN H
32 H H CH(CH3)2 H H
33 H CH(CH3)2 H H H
34 H H H CH(CH3)2 H
35 H H H t-Bu H
36 H H SCH3 H H
37 H SCH3 H H H
38 H H H SCH3 H
39 H H SCF3 H H
40 H SCF3 H H H
41 H H H SCF3 H
42 H H COCH3 H H
43 H COCH3 H H H
44 H H H COCH3 H
45 H H SOCH3 H H
46 H SOCH3 H H H
47 H H H SOCH3 H
48 H H SO2CH3 H H
49 H SO2CH3 H H H
50 H H H SO2CH3 H
51 H H OCHF2 H H
52 H OCHF2 H H H
53 H H H OCHF2 H
54 H H CO2CH3 H H
55 H CO2CH3 H H H
56 H H H CO2CH3 H
57 H H N(CH3)2 H H
58 H N(CH3)2 H H H
59 H H H N(CH3)2 H
60 H H N(C2H5)2 H H
61 H N(C2H5)2 H H H
62 H H H N(C2H5)2 H
63 H H NHCOCH3 H H
64 H NHCOCH3 H H H
65 H H H NHCOCH3 H
66 H H NHSO2CH3 H H
67 H NHSO2CH3 H H H
68 H H H NHSO2CH3 H
69 H H OCH2CH＝CH2 H H
70 H OCH2CH＝CH2 H H H
71 H H H OCH2CH＝CH2 H
72 H H OCH2C≡CH H H
73 H OCH2C≡CH H H H
74 H H H OCH2C≡CH H
75 H F F H H
76 H H F F H
77 F H F H H
78 H H F H F
79 H F H F H
80 F F H H H
81 H Cl Cl H H
82 H H Cl Cl H
83 Cl H Cl H H
84 H H Cl H Cl
85 H Cl H Cl H
86 Cl Cl H H H
87 H H NO2 NO2 H
88 NO2 H NO2 H H
89 H H NO2 H NO2
90 NO2 NO2 H H H
91 H H CN CN H
92 CN H CN H H
93 H H CN H CN
94 CN CN H H H
95 H CH3 CH3 H H
96 H H CH3 CH3 H
97 CH3 H CH3 H H
98 H H CH3 H CH3
99 H CH3 H CH3 H
100 CH3 CH3 H H H
101 H H CF3 CF3 H
102 CF3 H CF3 H H
103 H H CF3 H CF3
104 CF3 CF3 H H H
105 H H OCF3 OCF3 H
106 OCF3 H OCF3 H H
107 H H OCF3 H OCF3
108 OCF3 OCF3 H H H
109 H Cl CH3 H H
110 H H CH3 Cl H
111 H Cl H CH3 H
112 H H Cl CH3 H
113 Cl H CH3 H H
114 H H CH3 H Cl
115 H CH3 Br H H
116 H CH3 H Cl H
117 H NO2 CH3 H H
118 H H CH3 NO2 H
119 H H CH3 OCH3 H
120 NO2 H CH3 H H
121 H H Cl CF3 H
122 CF3 H Cl H H
123 H H Cl NO2 H
124 NO2 H Cl H H
125 H H CF3 Br H
126 H H CF3 NO2 H
127 H CF3 H NO2 H
128 H CF3 H Cl H
129 H H F CN H
130 H H Cl CN H
131 H H NO2 CN H
132 H H NO2 CH3 H
133 H H NO2 CF3 H
134 H H NO2 Cl H
135 Cl H NO2 H H
136 H NO2 H CH3 H
137 H NO2 H Cl H
138 H F CN H H
139 H H CN NO2 H
140 H H CN Cl H
141 CH3 H CN H H
142 H Cl Cl Cl H
143 Cl Cl Cl H H
144 Cl H Cl Cl H
145 H H Cl Cl Cl
146 Cl Cl H Cl H
147 H H CH3 CH3 CH3
148 H H OCH3 OCH3 OCH3
149 H Cl Cl Br H
150 H H F F Cl
151 H H CH3 Br Br
152 H H CF3 Cl Cl
153 H H CF3 Br Br
154 H H F Cl Br
155 H H Cl NO2 Cl
156 H H Br NO2 Br
157 H H Cl CN Cl
158 H H Cl CF3 Cl
159 H H Br CF3 Br
160 H CH3 Cl H Cl
161 H H Cl CONH2 Cl
162 H H Cl CO2CH3 Cl
163 H H Cl NHCOCH3 Cl
164 H H Cl OCF3 Cl
165 H H Br F Br
166 H H Br CH3 Br
167 H H Cl COCH3 Cl
168 Cl H Cl NO2 H
169 H H F F Cl
170 H H Cl CF3 Br
171 H H CH3 NO2 Cl
172 H H CH3 NO2 Br
173 H H CH3 Cl NO2
174 H H CH3 Br NO2
175 H H NO2 CF3 Cl
176 H H NO2 CF3 Br
177 H H F Br Br
178 H H CN Cl Cl
179 H H CN Br Br
180 F F F H F
Table 6: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 181-360.
Table 7: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 361-540.
Table 8: when A ═ NH, R1＝Cl，R2＝OCF3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Corresponding to 1-180 in Table 5 in sequence in accordance with Table 5, the compound number is 541-720.
Table 9: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 721-900.
Table 10: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 901-1080.
Table 11: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is 1081-1260.
Table 12: when A ═ NH, R1＝CH3，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the compound is represented by the number 1261-1440.
Table 13: when A ═ NH, R1＝C2H5，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 1441-1620.
Table 14: when A ═ NH, R1＝CHF2，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 1621-1800.
Table 15: when A ═ NH, R1＝CF3，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compounds are numbered 1801-1980.
Table 16: when A ═ NH, R1＝CH3，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 1981-2160.
Table 17: when A ═ NH, R1＝C2H5，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 2161-2340.
Table 18: when A ═ NH, R1＝CHF2，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compounds are numbered 2341-2520.
Table 19: when A ═ NH, R1＝CF3，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, represent the compound number 2521-2700.
Table 20: when A ═ NH, R1＝CH3，R2＝OC2H5，R3＝X2＝X3When H is substitutedRadical R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 2701-2880.
Table 21: when A ═ NH, R1＝C2H5，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, compound numbers 2881-3060.
Table 22: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10Consistent with Table 5, representative compound numbers 3061-3240.
Table 23: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 3241-3420.
Table 24: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 3421-3600.
Table 25: when A ═ NH, R1＝CH3，R2＝OH，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 3601-3780.
Table 26: when A ═ NH, R1＝CH3，R2＝OCH3，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 3781-3960.
Table 27: when A ═ NH, R1＝CH3，R2＝OC2H5，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 3961-4140.
Table 28: when A ═ NH, R1＝C2H5，R2＝OH，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 4141-4320.
Table 29: when A ═ NH, R1＝C2H5，R2＝OCH3，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 4321-4500.
Table 30: when A ═ NH, R1＝C2H5，R2＝OC2H5，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 4501-4680.
Table 31: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, representative compound numbers 4681-4860.
Table 32: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10Watch and watch5 correspond to the compound with the number 4861-5040.
Table 33: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 5041-5220.
Table 34: when A ═ NH, R1＝CH3，R2＝OH，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 5221-5400.
Table 35: when A ═ NH, R1＝CH3，R2＝OCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 5401-5580.
Table 36: when A ═ NH, R1＝CH3，R2＝OC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is No. 5581-5760.
Table 37: when A ═ NH, R1＝C2H5，R2＝OH，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 5761-5940.
Table 38: when A ═ NH, R1＝C2H5，R2＝OCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound number is5941-6120。
Table 39: when A ═ NH, R1＝C2H5，R2＝OC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, representative compound number 6121-6300.
Table 40: when A ═ NH, R1＝Cl，R2＝NH2，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is 6301-6480.
Table 41: when A ═ NH, R1＝Cl，R2＝NHCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the compound is represented by the number 6481-6660.
Table 42: when A ═ NH, R1＝Cl，R2＝NHC2H5，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, compound numbers 6661-6840 are represented.
Table 43: when A ═ NH, R1＝Cl，R2＝NH2，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the numbers for the representative compounds are 6841-7020.
Table 44: when A ═ NH, R1＝Cl，R2＝NHCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 7021-7200.
Table 45: when A ═ NH, R1＝Cl，R2＝NHC2H5，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 7201-7380.
Table 46: when A ═ NH, R1＝Cl，R2＝NH2，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound number is 7381-7560.
Table 47: when A ═ NH, R1＝Cl，R2＝NHCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 7561-7740.
Table 48: when A ═ NH, R1＝Cl，R2＝NHC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 7741-7920.
Table 49: when A ═ O, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 7921-8100.
Table 50: when A ═ O, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compounds are numbered 8101-8280.
Table 51: when A ═ O, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Table 5Consistently, the representative compound is numbered 8281-8460.
Table 52: when A ═ O, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 8461-8640.
Table 53: when A ═ O, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 8821-9000.
Table 54: when A ═ O, R1＝Cl，R2＝OC2H5，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 9001-9180.
Table 55: when A ═ S, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 9181-9360.
Table 56: when A ═ S, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is identified by the numbers 9361-9540.
Table 57: when A ═ S, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 9541-9720.
Table 58: when A ═ S, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When being ClSubstituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 9721-9900.
Table 59: when A ═ S, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 9901-10080.
Table 60: when A ═ S, R1＝Cl，R2＝OC2H5，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10In agreement with Table 5, compound numbers 10081-10260.
In the general formula I-B,
Figure BDA0000733339380000211
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Are different substituents, see Table 61, and represent compound numbers 10261-10350.
Watch 61
Numbering R6 R7 R9 R10
10261 H H H H
10262 H H H F
10263 H H F H
10264 H F H H
10265 F H H H
10266 H H H Cl
10267 H H Cl H
10268 H Cl H H
10269 Cl H H H
10270 H H H Br
10271 H H Br H
10272 H Br H H
10273 Br H H H
10274 H H H NO2
10275 H H NO2 H
10276 H NO2 H H
10277 NO2 H H H
10278 H H H CN
10279 H H CN H
10280 H CN H H
10281 CN H H H
10282 H H H CF3
10283 H H CF3 H
10284 H CF3 H H
10285 CF3 H H H
10286 H H H CH3
10287 H H CH3 H
10288 H CH3 H H
10289 CH3 H H H
10290 H H H OCH3
10291 H H OCH3 H
10292 H OCH3 H H
10293 OCH3 H H H
10294 H H H OCF3
10295 H H OCF3 H
10296 H OCF3 H H
10297 OCF3 H H H
10298 H H Cl Cl
10299 Cl Cl H H
10300 Cl H H Cl
10301 H Cl Cl H
10302 Cl H Cl H
10303 H Cl H Cl
10304 H H NO2 Cl
10305 H H CN Cl
10306 H H CF3 Cl
10307 H H NO2 Br
10308 Cl H H NO2
10309 H H Cl NO2
10310 H H CN CH3
10311 CH3 H Br H
10312 CH3 H NO2 H
10313 CH3 CH3 H H
10314 H H Cl CF3
10315 H Cl H CF3
10316 H CN H F
10317 F H H CN
10318 H H CN F
10319 F CN H H
10320 H H OCH3 OCH3
10321 H Cl Cl Cl
10322 Cl Cl Cl H
10323 Cl H Cl Cl
10324 Cl Cl H Cl
10325 Cl H Br F
10326 Br H Br Br
10327 Br Br H Br
10328 F H F F
10329 F F H F
10330 CH3 H CH3 CH3
10331 CH3 CH3 H CH3
10332 CH3 CH3 H Cl
10333 Cl H CH3 CH3
10334 CH3 CH3 H Br
10335 Br H CH3 CH3
10336 CH3 H Cl Cl
10337 Cl Cl H CH3
10338 H Cl CF3 Br
10339 Cl H Cl CH3
10340 CH3 H Br Br
10341 F F F F
10342 Cl Cl Cl Cl
10343 Br Br Br Br
10344 CH3 CH3 CH3 CH3
10345 Cl Cl F F
10346 Cl Cl CH3 CH3
10347 Cl Cl CN CN
10348 Br Br CN CN
10349 CH3 CH3 Cl Cl
10350 I I I I
Table 62: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound number 10351-10440.
Table 63: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 10441-10530.
Table 64: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is compound No. 10531-10620.
Table 65: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 10621-10710.
Table 66: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 10711-10800.
Table 67: when A ═ NH, R1＝CH3，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound number is 10801-10890.
Table 68: when A ═ NH, R1＝C2H5，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is No. 10891-10980.
Table 69: when A ═ NH, R1＝CHF2，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, representative compounds are numbered 10981-11070.
Table 70: when A ═ NH, R1＝CF3，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 11071-11160.
Table 71: when A ═ NH, R1＝CH3，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 11161-11250.
Table 72: when A ═ NH, R1＝C2H5，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 11251-11340.
Table 73: when A ═ NH, R1＝CHF2，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 11341-11430.
Table 74: when A ═ NH, R1＝CF3，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, represents the compound number 11431-11530.
Table 75: when A ═ NH, R1＝CH3，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 11521-11610.
Table 76: when A ═ NH, R1＝C2H5，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Table 61 is identical and represents the compound number 11611-11700.
Table 77: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10Consistent with Table 61, representative compound number 11701-11790.
Table 78: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 11791-11880.
Table 79: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10In agreement with Table 61, represents compound number 11881-11970.
Table 80: when A ═ NH, R1＝CH3，R2＝OH，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10In agreement with Table 61, the representative compound is 11971-12060.
Table 81: when A ═ NH, R1＝CH3，R2＝OCH3，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 12061-12150.
Table 82: when A ═ NH, R1＝CH3，R2＝OC2H5，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 12151-12240.
Table 83: when A ═ NH, R1＝C2H5，R2＝OH，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 12241-12330.
Table 84: when A ═ NH, R1＝C2H5，R2＝OCH3，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 12331-12420.
Table 85: when A ═ NH, R1＝C2H5，R2＝OC2H5，R3＝X2When H is equal to X3＝OCH3When the substituent R is6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 12421-12510.
Table 86: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 12511-12600.
Table 87: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the compound numbers 12601-12690.
Table 88: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the compound is identified by the numbers 12691-12780.
Table 89: when A ═ NH, R1＝CH3，R2＝OH，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 12781-12870.
Table 90: when A ═ NH, R1＝CH3，R2＝OCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is compound No. 12871-12960.
Table 91: when A ═ NH, R1＝CH3，R2＝OC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is identified by the numbers 12961-13050.
Table 92: when A ═ NH, R1＝C2H5，R2＝OH，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 13051-13140.
Table 93: when A ═ NH, R1＝C2H5，R2＝OCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 13141-13230.
Table 94: when A ═ NH, R1＝C2H5，R2＝OC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is 13231-13320.
Table 95: when A ═ NH, R1＝Cl，R2＝NH2，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 13321-13410。
Table 96: when A ═ NH, R1＝Cl，R2＝NHCH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 13411-13500.
Table 97: when A ═ NH, R1＝Cl，R2＝NHC2H5，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound number 13501-13590.
Table 98: when A ═ NH, R1＝Cl，R2＝NH2，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is number 13591-13680.
Table 99: when A ═ NH, R1＝Cl，R2＝NHCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 13681-13770.
Table 100: when A ═ NH, R1＝Cl，R2＝NHC2H5，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is code No. 13771-13860.
Table 101: when A ═ NH, R1＝Cl，R2＝NH2，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound numbers 13861-13950.
Table 102: when A ═ NH, R1＝Cl，R2＝NHCH3，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound number 13951-14040.
Table 103: when A ═ NH, R1＝Cl，R2＝NHC2H5，R3＝CH3，X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 14041-14130.
In the general formula I-C, the compound,
Figure BDA0000733339380000251
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R8、R9、R10Are different substituents, see Table 104, for compounds numbered 14131-14150.
Table 104
Numbering R6 R8 R9 R10
14131 H H H H
14132 H Cl H H
14133 H OCH3 H H
14134 H OCH2CF3 H H
14135 H H H CH3
14136 H H H CF3
14137 H H Br H
14138 H H CF3 H
14139 H H CF3 Cl
14140 H H OCH3 H
14141 Cl Cl H H
14142 H Cl Cl H
14143 Cl H Cl H
14144 H Cl H CH3
14145 CH3 Cl H H
14146 H Cl CH3 H
14147 H Cl Cl CF3
14148 Cl H NHCH3 H
14149 Cl H SO2CH3 H
14150 H Cl Cl Cl
Table 105: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R8、R9、R10Consistent with Table 104, the representative compound is numbered 14151-14170.
Table 106: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R8、R9、R10Consistent with Table 104, the representative compound is numbered 14171-14190.
Table 107: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R8、R9、R10Consistent with Table 104, the representative compound is numbered 14191-14210.
Table 108: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R8、R9、R10Consistent with Table 104, the representative compound is numbered 14211-14230.
Table 109: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2When H is equal to X3When Cl, the substituent R6、R8、R9、R10Consistent with Table 104, the numbers of compounds are 14231-14250.
Table 110: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R8、R9、R10Consistent with Table 104, the representative compound is numbered 14251-14270.
Table 111: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R8、R9、R10Consistent with Table 104, the representative compound is numbered 14271-14290.
Table 112: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝CH3When, X2＝X3When H, the substituent R6、R8、R9、R10Consistent with Table 104, compound number 14291-14310 is represented.
In the general formula I-D,
Figure BDA0000733339380000261
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R10Are different substituents, see Table 113, and represent compound number 14311-14320.
Watch 113
Numbering R6 R7 R8 R10
14311 Cl H H H
14312 H H H Br
14313 H H Cl Cl
14314 OCH3 H H H
14315 OCH3 OCH3 H H
14316 OCH3 Cl H H
14317 NHCH3 Cl H H
14318 Cl Cl Cl Cl
14319 Cl H Cl H
14320 Cl Cl H H
Table 114: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R10Consistent with Table 113, representative compound number 14321-14330.
Table 115: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R8、R10Consistent with Table 113, representative compound number 14331-14340.
Table 116: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R10Consistent with Table 113, representative compound number 14341-14350.
Table 117: when A is＝NH，R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R10Consistent with Table 113, representative compound number 14351-14360.
Table 118: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R8、R10In agreement with Table 113, representative compound number 14361-14370.
Table 119: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R8、R10Consistent with Table 113, representative compound number 14371-14380.
In the general formula I-E, the compound is shown in the specification,
Figure BDA0000733339380000271
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R9Are different substituents, see Table 120, and represent compound number 14381-14386.
Watch 120
Numbering R6 R7 R9
14381 H H H
14382 Cl H H
14383 CH3 H H
14384 CH3 CH3 H
14385 OCH3 OCH3 H
14386 Cl Cl H
Table 121: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R9Consistent with Table 120, representative compound number 14387-14392.
Table 122: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R9Consistent with Table 120, representative compound number 14393-14398.
Table 123: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9Consistent with Table 120, representative compound number 14399-14404.
Table 124: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9Consistent with Table 120, representative compound number 14405-14410.
Table 125: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R9Consistent with Table 120, representative compound numbers 14411-14416.
Table 126: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R9Consistent with Table 120, the representative compound is numbered 14417-14422.
In the general formula I-F,
Figure BDA0000733339380000281
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R10Are different substituents, see Table 127, for compounds numbered 14423-14427.
Watch 127
Numbering R6 R7 R10
14423 H H H
14424 Cl H H
14425 Cl CH3 H
14426 Cl H Cl
14427 Cl Cl Cl
Table 128: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, the representative compound is numbered 14428-14432.
Table 129: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R10In agreement with Table 127, represents the compound number 14433-14437.
Table 130: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R10Consistent with Table 127, represents compound numbers 14438-14442.
Table 131: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R10Consistent with Table 127, representative compound number 14443-14447.
Table 132: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, representative compound numbers 14448-14452.
Table 133: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, represents compound number 14453-14457.
In the general formula I-G,
Figure BDA0000733339380000282
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R8、R9Are different substituents, see Table 134, for compounds numbered 14458-14459.
Table 134
Numbering R6 R8 R9
14458 H H H
14459 Cl H H
Table 135: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 14460-14461.
Table 136: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 14462-14463.
Table 137: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R8、R9Consistent with Table 134, representative compound numbers 14464-14465.
Table 138: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 14466-14467.
Table 139: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, representative compound numbers 14468-14469.
Table 140: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 14470-14471.
In the general formula I-H, the compound is shown in the specification,
Figure BDA0000733339380000291
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R9、R10Are different substituents, see Table 141, and represent compounds numbered 14472-14473.
Table 141
Numbering R6 R9 R10
14472 H H H
14473 H Cl H
Table 142: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R9、R10Consistent with Table 141, represents compound number 14474-14475.
Table 143: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R9、R10Consistent with Table 141, representative compound numbers 14476-14477.
Table 144: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R9、R10Consistent with Table 141, the representative compound is numbered 14478-14479.
Table 145: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R9、R10Consistent with Table 141, representative compound numbers 14480-14481.
Table 146: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R9、R10Consistent with Table 141, representative compound numbers 14482-14483.
Table 147: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R9、R10Consistent with Table 141, representative compound numbers 14484-14485.
In the general formula I-I,
Figure BDA0000733339380000301
when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7Are different substituents, see Table 148, for compounds numbered 14486-14488.
Watch 148
Numbering R6 R7
14486 H H
14487 H Cl
14488 Cl Cl
Table 149: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7Consistent with Table 148, representative compounds are numbered 14489-14491.
Table 150: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7Consistent with Table 148, the representative compound is numbered 14492-14494.
Table 151: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7Consistent with Table 148, the representative compound is numbered 14495-14497.
Table 152: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7Consistent with Table 148, the representative compound is numbered 14498-14500.
Table 153: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R7Consistent with Table 148, compound No. 14501-14503.
Table 154: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7Consistent with Table 148, compound No. 14504-14506.
In the general formula I-K, the compound,
Figure BDA0000733339380000302
table 155: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, compound No. 14507-14686.
Table 156: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 14687-14866.
Table 157: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 14867-15046.
Table 158: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 15047-15226.
Table 159: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is compound number 15227-.
Table 160: when A ═ NH, R1＝Cl，R2＝OCH2CH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is 15407-15586.
Table 161: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 15587-15766.
Table 162: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 15767-15946.
Table 163: when A ═ NH, R1＝Cl，R2＝OCH2CH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 15947-16126.
In the general formula I-L,
Figure BDA0000733339380000311
table 164: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound number 16127-16216.
Table 165: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 16217-16306.
Table 166: when A ═ NH, R1＝Cl，R2＝OC2H5，R3＝X2＝X3When H, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound number 16307-16396.
Table 167: when A ═ NH, R1＝Cl，R2＝OH，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound is numbered 16397-16486.
Table 168: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound number 16487-16576.
Table 169: when A ═ NH, R1＝Cl，R2＝OCH2CH3，R3＝X2When H is equal to X3When Cl, the substituent R6、R7、R9、R10Consistent with Table 61, representative compound number 16577-16666.
Table 170: when A ═ NH, R1＝Cl，R2＝OH，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 16667-16756.
Table 171: when A ═ NH, R1＝Cl，R2＝OCH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 16757 and 16846.
Table 172: when A ═ NH, R1＝Cl，R2＝OCH2CH3，R3＝CH3When, X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 16847-169936.
In the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11See Table 173 for representativenessThe compound was numbered 169937-17076.
Watch 173
Figure BDA0000733339380000312
Figure BDA0000733339380000321
Figure BDA0000733339380000331
Table 174: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, representative compound number 17077-17216.
Table 175: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R8＝R10As Cl, substituent R11In agreement with Table 173, the representative compound is numbered 17217-17356.
Table 176: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3When H, R6＝R7＝R8＝R9＝R10As Cl, substituent R11Consistent with Table 173, compound numbers 17357-17496 are represented.
Table 177: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, represents a combinationItem number 17497-.
Table 178: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11In agreement with Table 173, compound No. 17637-17776.
Table 179: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, representative compound number 17777-17916.
Table 180: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, compound No. 17917-18056.
Table 181: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R8＝R10As Cl, substituent R11Consistent with Table 173, representative compound number 18057-18196.
Table 182: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3When H, R6＝R7＝R8＝R9＝R10As Cl, substituent R11Consistent with Table 173, the representative compound is numbered 18197 and 18336.
Table 183: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, the representative compound is numbered 18337-18476.
Table 184: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, compound number 18477-18616 is represented.
Table 185: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, the representative compound is numbered 18617-18756.
Table 186: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R8＝R10As Cl, substituent R11In agreement with Table 173, the representative compound is numbered 18757-18896.
Table 187: in the general formula I-A, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3When H, R6＝R7＝R8＝R9＝R10As Cl, substituent R11In agreement with Table 173, representative compound number 18897-19036.
Table 188: in the general formula I-B, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Is consistent with table 173The Table compound is numbered 19037-19176.
Table 189: in the general formula I-B, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, representative compound number 19177-19316.
Table 190: in the general formula I-B, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 19317-19456.
Table 191: in the general formula I-B, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, compound number 19457-19596 is represented.
Table 192: in the general formula I-B, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, representative compound number 19597-19736.
Table 193: in the general formula I-B, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, representative compounds are numbered 19737-19876.
Table 194: in the general formulae I-E, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R9When H, R6＝R7As Cl, substituent R11Consistent with Table 173, representative compound number 19877-20016.
Table 195: in the general formulae I-E, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R9When H, R6＝R7As Cl, substituent R11Consistent with table 173, compound No. 20017-20156 is represented.
Table 196: in the general formulae I-E, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R9When H, R6＝R7As Cl, substituent R11Consistent with table 173, representative compound number 20157-20296.
TABLE 197: in the general formulae I-E, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R9When H, R6＝R7＝OCH3Substituent R11Consistent with Table 173, compound number 20297-20436 is represented.
Table 198: in the general formulae I-E, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R9When H, R6＝R7＝OCH3Substituent R11Consistent with Table 173, compound numbers 20437-20576 are represented.
Table 199: in the general formulae I-E, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R9When H, R6＝R7＝OCH3Substituent R11In agreement with Table 173, compound No. 20577-20716 is represented.
Table 200: in the general formula I-F, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R10When H, R6＝Cl，R7＝CH3Get itSubstituent R11In agreement with Table 173, representative compound number 20717-.
Table 201: in the general formula I-F, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R10When H, R6＝Cl，R7＝CH3Substituent R11In agreement with Table 173, representative compound number 20857-20996.
Table 202: in the general formula I-F, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R10When H, R6＝Cl，R7＝CH3Substituent R11Consistent with Table 173, compound number 20997-21136 is represented.
Table 203: in the general formula I-H, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R10When H, R9As Cl, substituent R11Consistent with Table 173, compound number 21137-21276 is represented.
Table 204: in the general formula I-H, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R10When H, R9As Cl, substituent R11Consistent with Table 173, compound number 21277-21416 is represented.
Table 205: in the general formula I-H, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R10When H, R9As Cl, substituent R11In agreement with Table 173, the representative compound is numbered 21417-21556.
Table 206: in the general formula I-K, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11In agreement with Table 173, the representative compound is numbered 21557-21696.
Table 207: in the general formula I-K, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11In agreement with Table 173, compound No. 21697-21836.
Table 208: in the general formula I-K, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11In agreement with Table 173, representative compound number 21837-21976.
Table 209: in the general formula I-K, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 21977-22116.
Table 210: in the general formula I-K, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 22117-22256.
Table 211: in the general formula I-K, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, representative compound is numbered 22257-22396.
Table 212: in the general formula I-L, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 22397-22536.
Table 213: in the general formula I-L, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 22537-22676.
Table 214: in the general formula I-L, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 22677-22816.
Table 215: in the general formula I-L, when A ═ NR11，R1＝Cl，R2＝OH，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, compound No. 22817-22956.
Table 216: in the general formula I-L, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, representative compound number 22957-23096.
Table 217: in the general formula I-L, when A ═ NR11，R1＝Cl，R2＝OC2H5，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, compound number 23097-23236 was represented.
Table 218: in the general formula I-L, when A ═ NR11，R1＝Cl，R2＝OCH3，X2＝X3＝R3When H, R6＝R7＝R9＝R10As Cl, substituent R11Consistent with Table 173, compound number 23237-23376 was represented.
The salts of some of the compounds of the present invention can be illustrated by the salts of the specific compounds listed in Table 219, but are not intended to limit the present invention.
TABLE 219 salts of partial Compounds
Figure BDA0000733339380000361
Figure BDA0000733339380000371
In the general formula I-a,
Figure BDA0000733339380000372
table 220: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, representative compound numbers 23403-23582.
Table 221: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compounds are numbered 23583-23762.
Table 222: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 23763-23942.
Table 223: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound is numbered 23943-24122.
Table 224: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 24123-24302.
Table 225: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compounds are numbered 24303-24482.
In the general formula I-b,
Figure BDA0000733339380000381
table 226: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 24483-245872.
Table 227: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 245254.
Table 228: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 24663-24752.
Table 229: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is number 24753-24842.
Table 230: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R7、R9、R10In agreement with Table 61, representative compound number 24843-24932.
Table 231: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound number is 24933-25022.
Table 232: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 25023-25112.
Table 233: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H is equal toSubstituent R6、R7、R9、R10Consistent with Table 61, the representative compound is numbered 25113-25202.
In the general formula I-c, the compound is represented by,
Figure BDA0000733339380000382
table 234: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R8、R9、R10Consistent with Table 104, the numbers of compounds 25203 and 25222 are indicated.
Table 235: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R8、R9、R10Consistent with Table 104, the numbers of compounds 25223 and 25242.
Table 236: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R8、R9、R10Consistent with Table 104, the numbers of compounds 25243 and 25262 are indicated.
Table 237: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R8、R9、R10Consistent with Table 104, the numbers of compounds 25263 and 25282.
Table 238: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝X2＝X3＝R4When H, the substituent R6、R8、R9、R10Corresponding to Table 104, represents the compoundsNumbered 25283 and 25302.
Table 239: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R8、R9、R10In agreement with Table 104, the representative compound is numbered 25303-25322.
In the general formula I-d,
Figure BDA0000733339380000391
table 240: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R8、R10In agreement with Table 113, the representative compound was numbered 25323-25332.
Table 241: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R10In agreement with Table 3113, the representative compound is numbered 25333-25342.
Table 242: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R8、R10In agreement with Table 113, the representative compound was numbered 25343-25352.
Table 243: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R10In agreement with Table 113, the representative compound was numbered 25353-25362.
Table 244: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R8、R10Consistent with Table 113, the representative compound is numbered 25363-25372.
Table 245: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R10In agreement with Table 113, the representative compound was numbered 2537-25382.
In the general formula I-e, the compounds of formula I-e,
Figure BDA0000733339380000392
table 246: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R9In agreement with Table 120, the representative compound is numbered 25383-25388.
Table 247: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9Consistent with Table 120, representative compound number 25389-25394.
Table 248: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R9In agreement with Table 120, the representative compound was numbered-25395-25400.
Table 249: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H is not substitutedR6、R7、R9Consistent with Table 120, the representative compound is numbered 25401 and 25406.
Table 250: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R9Consistent with Table 120, the representative compound is numbered 25407 and 25412.
Table 251: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9Consistent with Table 120, the representative compound is numbered 25413-25418.
In the general formula I-f,
Figure BDA0000733339380000401
table 252: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, the compound number 25419-25423.
Table 253: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, the numbers of compounds 25424 and 25428 are indicated.
Table 254: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R10In agreement with Table 127, the representative compound was numbered 25429-25433.
Table 255: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, compound numbers 25434-25438 were represented.
Table 256: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, the representative compound was numbered 25439-25443.
Table 257: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R10Consistent with Table 127, representative compound number 25444-25448.
In the general formula I-g,
Figure BDA0000733339380000402
table 258: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R8、R9In agreement with Table 134, the representative compound was numbered 25449-25450.
Table 259: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 25451 and 25452.
Table 260: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered-25453-25454.
Table 261: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 25455-25456.
Table 262: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 25457-25458.
Table 263: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R8、R9Consistent with Table 134, the representative compound is numbered 25459-.
In the general formula I-h,
Figure BDA0000733339380000411
table 264: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R9、R10Consistent with Table 141, compound number 25461-25462.
Table 265: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R9、R10In agreement with Table 141, the representative compound is numbered 25463 and 25464.
Table 266: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R9、R10In agreement with Table 141, the representative compound number was 25465-25466.
TABLE 267: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R9、R10In agreement with Table 141, the representative compound was numbered 25467-25468.
Table 268: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R9、R10In agreement with Table 141, the representative compound is numbered 25469-25470.
Table 269: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R9、R10In agreement with Table 141, the representative compound was numbered 25471-.
In the general formula I-I,
Figure BDA0000733339380000412
table 270: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7Consistent with Table 148, compound numbers 25473 and 25475 were represented.
Table 271: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7In agreement with Table 148, representative CompoundsNumber 25476 and 25478.
Table 272: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7In agreement with Table 148, the representative compound was numbered 25479-25481.
TABLE 273: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7Consistent with Table 148, compound numbers 25482 and 25484 are represented.
Table 274: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7Consistent with Table 148, the representative compound is numbered 25485 and 25487.
Table 275: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7In agreement with Table 148, the representative compound was numbered 25488-25490.
In the general formula I-k, the alkyl group,
Figure BDA0000733339380000421
table 276: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 25491-25670.
Table 277: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, representative compound was numbered 25671-25850.
Table 278: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 25851-.
Table 279: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, representative compound number 26031-26210.
Table 280: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R8、R9、R10Consistent with Table 5, the representative compound is numbered 26211-26390.
Table 281: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R8、R9、R10In agreement with Table 5, the representative compound is numbered 26391-26570.
In the general formula I-l,
Figure BDA0000733339380000422
table 282: when A ═ NH, R1＝Cl，R2＝OH，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 26571-26660.
Table 283: when A ═ NH, R1＝Cl，R2＝OH，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 26661-26750.
Table 284: when A ═ NH, R1＝Cl，R2＝OCH3，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 26751-26840.
Table 285: when A ═ NH, R1＝Cl，R2＝OCH3，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is No. 26841-26930.
Table 286: when A ═ NH, R1＝Cl，R2＝OC2H5，R5＝CH3，R3＝R4＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, the representative compound is numbered 26931-27020.
Table 287: when A ═ NH, R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，R3＝X2＝X3When H, the substituent R6、R7、R9、R10In agreement with Table 61, representative compound number 27021-27110.
Table 288: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, representative compound is numbered 27111-27250.
Table 289: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 27251-27390.
Table 290: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, compound number 27391-27530.
Table 291: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, the representative compound is numbered 27531-27670.
Table 292: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, the representative compound is numbered 27671-27810.
Table 293: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, compound number 27811-27950.
Table 294: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, the representative compound is numbered 27951-28090.
Table 295: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound numbers 28091 and 28230.
Table 296: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, compound numbers 28231 and 28370 are represented.
Table 297: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11In agreement with Table 173, the representative compound is numbered 28371-28510.
Table 298: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 28511-28650.
Table 299: in the general formula I-a, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, the representative compound is numbered 28651-28790.
Table 300: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, the representative compound is numbered 28791-29070.
Table 301: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, the representative compound is numbered 29071-29210.
Table 302: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound number 29211-29350 is represented.
Table 303: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound number 29351-29490 was represented.
Table 304: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, representative compound is numbered 29491-29630.
Table 305: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound No. 29631-29770 was represented.
Table 306: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, compound number 29771-29910 is represented.
Table 307: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, the representative compound numbers 29911-30050.
Table 308: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, the representative compound numbers 30051-30190.
Table 309: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, the representative compound is numbered 30191-30330.
Table 310: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, the representative compound is numbered 30331-30470.
Table 311: in the general formula I-b, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, compound No. 30471-30610.
Table 312: in the general formula I-e, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R9When H, R6＝R7＝OCH3Substituent R11In agreement with Table 173, compound No. 30611-30750.
Table 313: in the general formula I-e, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R9When H, R6＝R7＝OCH3Substituent R11Consistent with Table 173, compound number 30751-30890 is represented.
Table 314: in the general formula I-e, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R9When H, R6＝R7＝OCH3Substituent R11Consistent with Table 173, compound number 30890-31030 is represented.
Table 315: in the general formula I-e, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R9When H, R6＝R7＝OCH3Substituent R11In agreement with Table 173, compound number 31031-31170.
Table 316: in the general formula I-e, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R9When H, R6＝R7＝OCH3Substituent R11In agreement with Table 173, compound No. 31171-31310.
Table 317: in the general formula I-e, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R9When H, R6＝R7＝OCH3Substituent R11In agreement with Table 173, the representative compound is numbered 31311-31450.
Table 318: in the general formula I-f, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R10When H, R6＝Cl，R7＝CH3Substituent R11Consistent with Table 173, the representative compound is numbered 31451-31590.
Table 319: in the general formula I-f, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R10When H, R6＝Cl，R7＝CH3Substituent R11In agreement with Table 173, representative compound number 31591-31730.
Table 320: in the general formula I-f, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R10When H, R6＝Cl，R7＝CH3Substituent R11Consistent with Table 173, compound numbers 31731-31870 are represented.
Table 321: in the general formula I-f, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R10When H, R6＝Cl，R7＝CH3Substituent R11In agreement with Table 173, the representative compound was numbered 31871-32010.
Table 322: in the general formula I-f, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R10When H, R6＝Cl，R7＝CH3Substituent R11Consistent with Table 173, compound number 32011-32150 is represented.
Table 323: in the general formula I-f, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R10When H, R6＝Cl，R7＝CH3Substituent R11Consistent with Table 173, the representative compound is numbered 32151-32290.
Table 324: in the general formula I-h, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R10When H, R9As Cl, substituent R11Consistent with Table 173, the representative compound is numbered 32291-32430.
Table 325: in the general formula I-h, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R10When H, R9As Cl, substituent R11In agreement with Table 173, the representative compound number was 32431-32570.
Table 326: in the general formula I-h, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R10When H, R9As Cl, substituent R11Consistent with Table 173, the representative compound is numbered 32571-32710.
TABLE 327: in the general formula I-h, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R10When H, R9As Cl, substituent R11In agreement with Table 173, the representative compound is numbered 32711-32850.
Table 328: in the general formula I-h, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R10When H, R9As Cl, substituent R11In agreement with Table 173, the representative compound is numbered 32851-32990.
Table 329: in the general formula I-h, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R10When H, R9As Cl, substituent R11In agreement with Table 173, compound number 32991-33130.
Table 330: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R4＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11In agreement with Table 173, compound number 33131-33270.
Table 331: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, the representative compound is numbered 33271-33410.
Table 332: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, the representative compound is Nos. 33411-33550.
Table 333: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, compound numbers 33551 and 33690 are shown.
Table 334: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11Consistent with Table 173, the representative compound is identified by the numbers 33691-33830.
Table 335: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8When H, R9＝CN，R10(ii) F, substituent R11In agreement with Table 173, the representative compound is 33831-33970.
Table 336: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound No. 33971-34110.
Table 337: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, compound number 34111-34250 is represented.
Table 338: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound number 34251-34390 is represented.
Table 339: in the general formula I-k, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R8＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound number 34391-34530 was represented.
Table 340: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound number 34531-34670 was represented.
Table 341: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, representative compound is numbered 34671-34810.
Table 342: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, compound number 34811-34950.
Table 343: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11In agreement with Table 173, the representative compound is numbered 34951-35090.
Table 344: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, the representative compound is numbered 35091-35230.
Table 345: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7＝R10When H, R9＝CF3Substituent R11Consistent with Table 173, representative compound number 35231-35370.
Table 346: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OH，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, representative compound number 35371-35510.
Table 347: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OH，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, representative compound number 35511-35650.
Table 348: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OCH3，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, representative compound number 35651-35790.
Table 349: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OCH3，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11In agreement with Table 173, representative compound number 35791-35930.
Table 350: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OC2H5，R5＝CH3，X2＝X3＝R3＝R4＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, the representative compound is numbered 35931-36070.
Table 351: in the general formula I-l, when A ═ NR11，R1＝Cl，R2＝OC2H5，R4＝R5＝CH3，X2＝X3＝R3＝R6＝R7When H, R9＝CF3，R10As Cl, substituent R11Consistent with Table 173, the representative compound is numbered 36071-36210.
The compounds of the invention are prepared according to the following process, wherein the radicals are as defined above unless otherwise stated: the preparation of compounds of formula I can be divided into the preparation of compounds of formula I-1 when a ═ NH; when A ═ NR11(however, R is not limited thereto11Not equal to H), preparation of compounds of general formula I-2; and when a ═ O or S, the preparation of compounds of general formula I-3, in particular respectively:
in the first case, when a ═ NH, the compound of formula I-1 can be prepared by the following three methods.
The method comprises the following steps: substituted pyrimidine chlorides were reacted with the corresponding substituted amines, as shown in the equation below. Reference is made to EP0370704, EP0356158, EP0264217, EP0665225, JP10036355, US4985426 for the synthesis process.
Figure BDA0000733339380000461
According to the above reaction scheme, the compound represented by the general formula I-1 can be prepared by condensing the substituted pyrimidine chloride represented by the general formula II with the amine represented by the general formula III in a suitable solvent.
The reaction is carried out in a suitable solvent, which may be selected from benzene, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, pyridine, dichloromethane, chloroform, dichloroethane, methyl acetate or ethyl acetate, etc. The reaction may be carried out in the presence or absence of a base, and when the reaction is carried out in the presence of a base, the reaction is accelerated. The base may be selected from alkali metal hydrides, such as sodium hydride; alkali metal hydroxides such as sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodium carbonate or potassium carbonate; organic amines, such as pyridine or triethylamine. The reaction temperature can be between room temperature and the boiling point temperature of the solvent, and is usually 20-100 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours.
Substituted pyrimidine chlorides of formula II are key intermediates for the preparation of compounds of formula I-1 and can be synthesized by methods described in documents CN103058935A, US4977264, Journal of the American Chemical Society, 79,1455(1957), Journal of the Chemical Society, p.p.3478-3481 (1955). The corresponding starting materials XII, XIV are commercially available.
Figure BDA0000733339380000462
According to the above reaction scheme, the substituted pyrimidine chloride represented by the general formula II can be prepared by condensing compound XII and XIV in a suitable solvent under suitable acid, alkali or neutral conditions.
The reaction is usually carried out in the range from room temperature to the boiling point of the solvent, and the reaction temperature is preferably 20 to 100 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours. Suitable solvents may be selected from, for example, methanol, ethanol, isopropanol, water, tetrahydrofuran, dioxane, N-dimethylformamide, N-methylpyrrolidone or dimethylsulfoxide, etc. Suitable bases may be selected from, for example, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, or sodium hydride, among others. Suitable acids may be selected from formic acid, acetic acid, propionic acid, hydrochloric acid, sulfuric acid, oxalic acid, nitric acid, phosphoric acid, and the like.
The amine compound shown in the general formula III or the salt thereof is a key intermediate for preparing the compound shown in the general formula I-1, and can be prepared by the following methods: specific reference is made to documents US4895849, JP10036355, EP665225, US20070093498, WO2007046809, US5783522A, WO02083647a1, CN1927860A, Organic Syntheses, col.vol.10, p.501 (2004); vol.75, p.61(1998) or Organic Syntheses, col.Vol.10, p.102 (2004); vol.75, p.53 (1998). The corresponding starting materials IV, V and VII are commercially available.
(1) The preparation method of the cyano reduction method comprises the following steps:
Figure BDA0000733339380000471
wherein L is a leaving group which is halogen, methyl sulfonate or p-toluene sulfonate, and M is an alkyl chain having one carbon less than B.
And (3) reacting the general formula IV with V in a proper solvent in the presence of a proper alkali, and processing to obtain VI. The preparation can be carried out by the method described in Fine chemistry, 2005,22(12): 944-. The reaction is usually carried out in the range from room temperature to the boiling point of the solvent, and the reaction temperature is preferably 20 to 100 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours. Suitable solvents may be selected from, for example, acetone, butanone, tetrahydrofuran, acetonitrile, toluene, xylene, benzene, N-dimethylformamide, dimethyl sulfoxide, methanol or ethanol, etc. Suitable bases may be selected from, for example, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, or sodium hydride, etc.
In a suitable solvent, VI is subjected to hydrogenation reduction in the presence of a suitable catalyst and ammonia water to obtain III. Specific preparations can be found in documents j.am.chem.soc,70,3788 (1948); 82,681 (1960); 82,2386 (1960); chem, 49,2990 (1971); chem,37,335 (1972); organic Syntheses, Coll.Vol.3, p.229, p.720(1955), Vol.23, p.71(1943) or Vol.27, p.18 (1947). The reaction is usually carried out in the range from room temperature to the boiling point of the solvent, and the reaction temperature is preferably 20 to 100 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours. Suitable solvents may be selected from methanol, ethanol, isopropanol, benzene, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, chloroform, dichloromethane, methyl acetate, ethyl acetate, tetrahydrofuran, dioxane, N-dimethylformamide, N-methylpyrrolidone, or dimethylsulfoxide, and the like. Suitable catalysts may be selected from raney nickel, palladium on carbon or platinum oxide and the like.
(2) Preparing amine and salt thereof by using substituted p-hydroxyphenylalkylamine as raw material:
Figure BDA0000733339380000472
in the formula, Boc2O means di-tert-butyl dicarbonate.
Firstly, in a proper solvent and in the presence of a proper alkali, di-tert-butyl dicarbonate reacts with corresponding p-hydroxyphenylalkylamine VII at 0-100 ℃ to prepare the Boc-protected p-hydroxyphenylalkylamine VIII. The reaction temperature is preferably 0-50 ℃; the reaction time is 30 minutes to 20 hours, preferably 0.5 to 10 hours. Suitable solvents are selected from benzene, toluene, xylene, chloroform, dichloromethane, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone or dimethylsulfoxide, etc.; suitable bases are selected from alkali metal carbonates such as sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate.
And then, performing condensation reaction on the VIII and the V in a proper solvent and in the presence of a proper alkali at 0-100 ℃ to obtain IX. The reaction time is 30 minutes to 20 hours, preferably 0.5 to 10 hours. Suitable solvents are selected from benzene, toluene, xylene, chloroform, dichloromethane, acetone, butanone, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone or dimethylsulfoxide, etc.; suitable bases are selected from alkali metal hydrides such as sodium hydride, alkali metal hydroxides such as sodium hydroxide or potassium hydroxide, alkali metal carbonates such as sodium carbonate or potassium carbonate, organic amines such as pyridine or triethylamine.
And deprotecting IX in a suitable solvent with a suitable acid to obtain a corresponding salt X, and alkalifying to obtain III. The reaction temperature is preferably 0-50 ℃; the reaction time is 30 minutes to 20 hours, preferably 0.5 to 10 hours. Suitable solvents are selected from ethyl acetate, methyl formate, benzene, toluene, xylene, chloroform, dichloromethane, water, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone, or dimethylsulfoxide, etc.; suitable acids are selected from hydrochloric acid, trifluoroacetic acid, sulfuric acid, acetic acid, propionic acid, butyric acid, oxalic acid, adipic acid, dodecanedioic acid, lauric acid, stearic acid, fumaric acid, maleic acid, benzoic acid, or phthalic acid, and the like; the base is selected from alkali metal hydrides such as sodium hydride, alkali metal hydroxides such as sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodium carbonate or potassium carbonate, organic amines such as pyridine or triethylamine. See WO2004093800A for a specific preparation method.
The second method comprises the following steps: the substituted pyrimidine chloride reacts with corresponding substituted p-hydroxyphenylalkylamine, and then is condensed with an intermediate V to obtain a target product I-1, wherein the reaction formula is as follows.
Figure BDA0000733339380000481
The compound represented by the general formula I-1 can be prepared by condensing substituted pyrimidine chloride shown in the general formula II with p-hydroxyphenylalkylamine shown in the general formula VII in a suitable solvent to prepare XI, and condensing the XI with an intermediate V under the action of alkali to prepare I-1.
The condensation reaction of II with VII is carried out in a suitable solvent, which may be selected from benzene, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, pyridine, dichloromethane, chloroform, dichloroethane, methyl acetate or ethyl acetate, etc. The reaction may be carried out in the presence or absence of a base, and when the reaction is carried out in the presence of a base, the reaction is accelerated. The base may be selected from metal hydrides, such as sodium hydride; alkali metal hydroxides such as sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodium carbonate or potassium carbonate; organic amines, such as pyridine or triethylamine. The reaction temperature can be between room temperature and the boiling point temperature of the solvent, and is usually 20-100 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours.
The condensation reaction of XI and V produced is carried out in a suitable solvent selected from benzene, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, tetrahydrofuran, acetonitrile, dioxane, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, pyridine, dichloromethane, chloroform, dichloroethane, methyl acetate or ethyl acetate, etc. The reaction is carried out in the presence of a base, which may be selected from metal hydrides, such as sodium hydride; alkali metal hydroxides such as sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodium carbonate or potassium carbonate; organic amines, such as pyridine or triethylamine. The reaction temperature may be between room temperature and the boiling point of the solvent, and is usually 20 to 200 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours. The specific preparation method is disclosed in JP11049759, EP0370704, EP0196524 and US 4895849.
The third method comprises the following steps: substituted pyrimidine chlorine XII reacts with corresponding substituted amine III, the obtained XIII is condensed with intermediate XIV, and the target product I-1 can be obtained, and the reaction formula is as follows. For the synthesis methods, reference is made to CN103058935A, EP0370704, EP0356158, EP0264217, EP0665225, JP10036355, US 4985426.
Figure BDA0000733339380000491
The process for preparing XIII by reacting intermediates XII and III is referred to as the first process for preparing the object I-1 by reacting intermediates II and III.
Reaction of XIII with intermediate XIV to prepare I-1 is carried out in a suitable solvent, with or without a base. The reaction is usually carried out in the range from room temperature to the boiling point of the solvent, and the reaction temperature is preferably 20 to 100 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours. Suitable solvents may be selected from, for example, tetrahydrofuran, acetonitrile, toluene, xylene, benzene, N-dimethylformamide, dichloromethane, chloroform, dichloroethane, dimethyl sulfoxide, methanol or ethanol, etc. Suitable bases may be selected from, for example, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, or the like.
The other raw materials involved in the process for preparing the compounds of the above general formula I-1 are, for example, those of the general formulae IV, V, VII, XII, XIV and Boc2All compounds represented by O are commercially available.
In the second case, when A ═ NR11(however, R is not limited thereto11Not equal to H), compounds of formula I-2 can be prepared by reference to the following references, JP08269021, JP3543411, JP1995-72621, JP1995-96669, JP3511729, JP08291149, EP530149, WO 9208704.
In the third case, when a ═ O or S, the preparation of the compounds of general formula I-3 refers to the processes described in patents WO2012075917, EP 534341.
A compound of the formula I-2 (R)11Not equal to H) and compounds of general formula I-3 (a ═ O or S) the structural formulae are as follows:
Figure BDA0000733339380000492
the preparation method of the compound salt of the general formula I comprises the following steps:
preparation of pyrimidinamine salt formation:
the compound of the general formula I-1 reacts with organic acid or inorganic acid to obtain corresponding salt I-1A, and the compound of the general formula I-2 reacts with organic acid or inorganic acid to obtain corresponding salt I-2A, wherein the reaction formula is as follows:
Figure BDA0000733339380000501
the salt-forming reaction of the compound shown in the general formula I-1 or the general formula I-2 and the organic acid or the inorganic acid is usually carried out within the range from room temperature to the boiling point temperature of the solvent, and the preferable reaction temperature is 20-100 ℃. The reaction time is 30 minutes to 20 hours, usually 1 to 10 hours. Suitable solvents may be selected from water, methanol, ethanol, isopropanol, benzene, toluene, xylene, acetone, methyl ethyl ketone, methyl isobutyl ketone, chloroform, dichloromethane, methyl acetate, ethyl acetate, tetrahydrofuran, dioxane, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, or the like.
Acids which may form salts with the compounds of formula I-1 or formula I-2 of the present invention include: carboxylic acids such as acetic acid, propionic acid, butyric acid, oxalic acid, trifluoroacetic acid, adipic acid, dodecanedioic acid, lauric acid, stearic acid, trifluoroacetic acid, fumaric acid, maleic acid, malic acid, citric acid, benzoic acid, p-toluic acid, phthalic acid, or the like; sulfonic acids such as methanesulfonic acid, 1, 3-propanedisulfonic acid, p-toluenesulfonic acid, dodecylbenzenesulfonic acid, or the like; and inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, carbonic acid, or the like, and further preferably hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, trifluoroacetic acid, methanesulfonic acid, or p-toluenesulfonic acid.
In addition, in the compounds of formula I, the nitrogen of the pyrimidine ring and other nitrogen-containing heterocycles can also form salts, and the preparation method can be referred to documents DE19647317, JP2001504473, US5925644, WO9822446, ZA9710187 and the like.
The compound of the general formula I shows excellent activity on various germs, pests and mites in agriculture or other fields. The compound of the general formula also overcomes the defect of higher toxicity of the same type of compounds, and greatly improves the toxicology aspect. Therefore, the technical scheme of the invention also comprises the application of the compound shown in the general formula I in preparing bactericides, insecticides and acaricides in the fields of agriculture, forestry or sanitation.
The examples of pests mentioned below are intended only to illustrate the invention, but in no way limit it.
The compounds of the general formula I can be used for controlling the following diseases: oomycete diseases such as downy mildew (cucumber downy mildew, rape downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, loofah downy mildew, wax gourd downy mildew, melon downy mildew, Chinese cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), white rust (rape white rust, Chinese cabbage white rust), damping-off (rape damping-off, tobacco damping-off, tomato damping-off, pepper damping-off, eggplant damping-off, cucumber damping-off, cotton seedling damping-off), cotton rot (hot pepper rot, loofah sponge rot, wax gourd blight), epidemic diseases (broad bean blight, cucumber blight, pumpkin blight, melon blight, hot pepper, leek blight, garlic blight, cotton blight, tomato blight, etc.; fungi imperfecti diseases such as wilt (sweet potato wilt, cotton wilt, sesame wilt, castor wilt, tomato wilt, bean wilt, cucumber wilt, pumpkin wilt, winter melon wilt, watermelon wilt, sweet melon wilt, hot pepper wilt, broad bean wilt, rape wilt, soybean wilt), root rot (hot pepper root rot, eggplant root rot, bean rot, cucumber root rot, bitter gourd root rot, cotton black root rot, broad bean root rot), damping off (seedling blight of cotton, sesame seedling blight, hot pepper seedling blight, cucumber damping off, cabbage stalk rot), anthracnose (sorghum anthracnose, cotton anthracnose, kenaf anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, mulberry leaf, hot pepper, bean disease, cucumber anthracnose, red sesame anthracnose, jute anthracnose, flax anthracnose, tobacco anthracnose, eggplant disease, hot pepper anthracnose, vegetable bean disease, and cucumber blight, Balsam pear anthracnose, pumpkin anthracnose, wax gourd anthracnose, watermelon anthracnose, melon anthracnose, litchi anthracnose), verticillium wilt (cotton verticillium wilt, sunflower verticillium wilt, tomato verticillium wilt, hot pepper verticillium wilt, eggplant verticillium wilt), scab (pumpkin scab, wax gourd scab, melon scab), gray mold (boll gray mold, red ramie gray mold, tomato gray mold, hot pepper gray mold, bean gray mold, celery gray mold, spinach gray mold, kiwi gray mold), brown spot (cotton brown spot, jute brown spot, beet brown spot, peanut brown spot, pepper brown spot, wax gourd brown spot, soybean brown spot, sunflower brown spot, pea brown spot, broad bean brown spot), black spot (flax brown spot, rape black spot, sesame black spot, sunflower black spot, castor black spot, tomato black spot, pepper black spot, eggplant black spot, bean black spot, cucumber black spot, celery black spot, carrot black rot, carrot black spot, apple black spot, peanut black spot), spot blight (tomato spot blight, pepper spot blight, celery spot blight), early blight (tomato early blight, pepper early blight, eggplant early blight, potato early blight, celery early blight), ring spot (soybean ring spot, sesame ring spot, bean ring spot), leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight), stem base rot (tomato stem base rot, bean stem base rot), and others (corn round spot, kenaf waist fold, rice blast, black sheath blight, sugarcane eye spot, cotton boll aspergillosis, peanut crown rot, soybean stem blight, soybean black spot, melon big spot, peanut net spot, tea leaf spot, red leaf spot, black leaf spot, peanut net spot, tea leaf spot, tomato black spot, potato leaf spot, potato black spot, tomato leaf, Pepper white spot disease, white gourd leaf spot disease, celery black rot disease, spinach heart rot disease, kenaf leaf mold disease, kenaf spot disease, jute stem spot disease, soybean purple spot disease, sesame leaf spot disease, castor gray spot disease, tea brown leaf spot disease, eggplant brown orbicular spot disease, kidney bean red spot disease, bitter gourd leukoderma, watermelon spot disease, jute bottom rot disease, sunflower root stem rot disease, kidney bean carbon rot disease, soybean target spot disease, eggplant rod spore leaf spot disease, cucumber target spot disease, tomato leaf mold, eggplant leaf mold, broad bean red spot disease and the like); basidiomycete diseases such as rust (wheat stripe rust, wheat stalk rust, wheat leaf rust, peanut rust, sunflower rust, sugarcane rust, leek rust, onion rust, chestnut rust, soybean rust), smut (maize head smut, maize smut, sorghum head smut, sorghum loose smut, sorghum stalk smut, chestnut kernel smut, sugarcane head smut, kidney bean rust) and others (such as wheat sharp eyespot, rice sheath blight, etc.); ascomycetous diseases, such as powdery mildew (wheat powdery mildew, rape powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, towel gourd powdery mildew, pumpkin powdery mildew, wax gourd powdery mildew, melon powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia rot (flax sclerotinia rot, rape sclerotinia rot, soybean sclerotinia rot, peanut sclerotinia rot, tobacco sclerotinia rot, pepper sclerotinia rot, eggplant sclerotinia rot, kidney bean sclerotinia rot, pea sclerotinia rot, cucumber sclerotinia rot, bitter gourd sclerotinia rot, wax gourd sclerotinia rot, watermelon sclerotinia rot, celery sclerotinia rot), scab (apple scab, pear scab) and the like. Particularly, the composition has good control effect on corn rust, rice blast, cucumber gray mold and cucumber downy mildew under lower dosage.
The compounds of the general formula I can be used for controlling the following pests:
coleoptera (Coleoptera) (beetle): bean species (Acanthoscelides spp.) (elephant), phaseolus vulgaris (Acanthoscelides obtectus) (common pisiform), Ceratoptera alba (Agrilus planipes) and Ceratopteris versicolor (Quadrifolia narrow Germin), Flammulina species (Agriotes spp.) (wireworm), Anoplophora glabripennis (Aphis longipes), Gomphytus species (Anthonoma spp.) (Arthrobacter flavidus), Gomphytus grandis (Anthronus grandis) (Arthrobacter asiaticus), Gomphytus species (Aphidius spp.) (Aprionus spp.) (Arthrospora), Cochlothiaoma sp. (Anacardia), Cochlothiajaponica (Aponia spp.) (grub), Cochlothuroides (Atacys specularis) (Black piss specula (Atanthus spec), Pieris versicolor (Pieris indica) (Pieris indica), Pieris indica (Pieris indica) (Pieris) and Pieris (Pieris indica) (Pieris chinensis (Pieris) of (Pieris) variety (Pieris illustrates (Pieris) and Pieris (Pieris) such as Pieris (Pieris sinensis (Pieris variety (Pieris) and Pieris (Pieris), Cacoesia species (Cacoesia spp.), Callosobruchus maculatus (Callosobruchus maculatus) (southern cowpea weevil), yellow spot dew beetle (Carpophilus hemiptera) (stemona), testudina caragana (Cassida vittata), longicorn species (ccroscrna spp.), cerrotoma species (Ccrotoma spp.), trichomonas sp (chrysomella), leuconychus (ceromorpha trifoliatus) (setaria viridis), chlorophyta species (ceromorpha spp.), elephantopus (ceromorpha spp.), Chinese cabbage turtle species (ceromorphus assius) (cabbage caterpillar), turnip elephant species (ceromorphus purpureus), western cabbage beetle (ceromorphus), western red beetle (collybia), western red beetle (ceromorphus flavus), red beetle (collybia), red beetle (collygus purpurea), red beetle (collygus purpurea), red beetle (collygus), red beetle (red beetle), red beetle (collygus), red beetle (red beetle) and red beetle (red beetle), red beetle (red beetle), red beetle (red beetle), red beetle (red beetle, Examples of such plants include, but are not limited to, Cryptolepis pusillus (Cryptolepis pulillus) (Aphelenchus fasciatus), Rhynchophyllus (Cryptolepis grain beetle), Ctenodera species (Ctenodera spp.) (nematodes), elephant species (Curculio spp.) (weevil), Rhinocephalus species (Cycleephora spp.) (Holotrichia dioides), Rhinocephalus degraphus (Hyponella fasciata) (Trichophyllus fasciatus), Rhinocephalus (Deporus marginatus) (Margarita fasciatus), Rhizophora paragua (Mesorus paraphyllus), Rhizophora paragua (Mesorus) (Pharmanopsis paraphyllus), Rhizophora striatus (Hypoglaucus) and Rhizophora leucotrichia (Meadora), Rhizophora leucotrichia (Piropis leucotrichia), Rhizophora leucotrichia (Piropis fasciata (Meadowrue), Rhizophora leucotrichia fasciata (Pilus) and Rhizophora) species (Meadowraenophora), Rhizophora fascicularia), Rhizophora (Piropis sp. (Pirophus fascicularis) and Rhizophyllus (Piropis) or Piropis sp. (Meadonis (Pirophus fascicularia) or Piropis (Piropis) or Pirophus fasciatus (Piropis) or A) or Piropis) or Pirophus fasciatus (Piropis) or Piropis (Pirophus fasciatus), Piropis fasci, Lucerne medicago sativa (hyperbaric) (medicago sativa), medicago species (hyperboes spp.) (argentina stem weevil (Hyperodes weevil)), coffee chervil (polyphnemus hamperei) (coffee chervil), scotland species (Ips spp.) (echinacea purpurea), tobacco beetle (Lasioderma serricorne) (tobacco beetle), potato beetle (leptotarsa decemlata) (colorado potato beetle), lipoglorys fuscus, lipogynys suturalis, rice water weevil (lisurena oryzophilus) (rice water weevil), silphigus species (lycospera spellensis), meldonia sp.) (meclizia purpurea/tenera), meldonia terrestris (meldonia), meldonia spp (meldonia spp.) (Mewlela spp.) (Mewlera), Mesorrel louse beetle (Mewlela spp.) (Messoides), Mesorrel louse beetle sporulata (Mewlela spp. (Messochloes sporea), Mewless beetle spp. (Messel beetle spruce) Rhinoceros rhynchophylla (oriycetes rhinoceros) (date palm beetle), ceremony saw beetle (oryzaephiulus mercator) (market saw beetle), cercaria terrestris (elephant), cercaria terrestris (odontobrama), cercaria species (oxytrophus spp), cercaria nigripes (auricle melas mellea) (orange leaf beetle), cercaria terrestris (auricle oryzae), cerbrotica rosea (purpureus), cercaria species (panomyopis p), panopis palustris (ostrinia nubilalis), cercaria terrestris (purpurea), cercaria macrotrichia (peruvignonensis), cercaria terrestris (purpurea), cercaria macrotrichia (pernya), cercaria stris (purpurea), cercaria macrotrichia terrestris (purpurea), cercaria terrestris (bullosa) (common beetle species), cercaria stringta (bullosa) (common beetle species (pink) (common beetle species), cerifera), cerbrotica striga (mangle), cerifera), cerbrotica striga (mangle), cercospinus mangle), cerifera (mangle) and cerifera) including rhizopus mangle (mangle) and cerifera (mangle, cerifera) including rhizopus mangle, cerifera, mangle, Root gill species (rhizomorphous spp.) (european scarab (european chafer)), cryptorhynchophorus species (ryophorus spp.) (elephant), silly species (Scolytus spp.) (wooddull moth), shonophorus species (shonophorus spp.) (cereal elephant), pisum sativum leaf (Sitona linkuntze) (pea leaf weevil (pca leaf weevil)), rice weevil species (Sitophilus spp.) (cereal weevil), rice elephant (Sitophilus grandis) (paddy insect (granavirus), rice elephant (Sitophilus oryzae) (rice weevil), rice paneum (stewartum), triphyllum sativum (triborum), and red beetle (Tribolium), red beetle (Tribolium sativum), red beetle (Tribolium), red beetle (red beetle), red beetle (red beetle, red.
Dermaptera (Dcrmaptcra) (earwigs).
Vein winged order (Dictyoptera) (cockroach): german cockroach (Blattella germanica) (German cockroach), blattaria orientalis (Blatta orientalis), Blatta palustris (Blatta cockroach), Blatta australiana (parcoblata penylvanica), Periplaneta americana (perilanta americana) (austria americana), Blatta australiana (australia cockroach)), Periplaneta fusca (pcripa rubra) (australia cockroach), Periplaneta fuliginosa (brown cockroach), Periplaneta smokosa (perilanta fuliginosa) (Periplaneta fuliginosa (cockroach)), and Periplaneta fuliginosa (brown cockroach) (Periplaneta subcapium (brown cockroach)), and Periplaneta fuligina (brown cockroach) (Periplaneta rubra americana (brown cockroach)).
Diptera (Diptera) (flies): mosquito species (Aedes spp.) (mosquito), lucerne fly larvae (Agromyza frontella) (alfa blotch), agromyzis species ((Agromyza spp.) (leaf miner), trypetid species (anastrep spp.) (fruit fly), garleria persica (anastrepa subsp.) (fruit fly), garleria persica (garleria persica) (garleria persica (tail fly)), mosquito species (anophes spp.) (mosquito), fruit fly species (batrachta spp.) (fruit fly), melon fly (Bactrocera bitrae) (melon), citrus fruit fly (Bactrocera persica), mosquito species (ceitis spp.) (mosquito), mosquito fly larvae (sea fly larvae) (sea fly), sea fly larvae (sea fly larvae) (deer spp.) (moth), sea fly larvae (sea fly larvae) (moth larvae) (bilus persica spp.) (fruit fly) (moth larvae) (mosquito larvae) (deer spp.) (fruit fly) (garrisb) (mosquito larvae) (sea fly) (moth) Leaf of rape mosquito (Dasineura brassicae) (cabbage mosquito), Dimochi species (Delia spp.), Grapholitha platura (root maggot (seed corn bug)), Drosophila species (Drosophila spp.) (vinegar fly), Musca species (Fannia spp.) (housefly), yellow belly fly (Fannia canthus) (summer fly (litter house fly)), Grey belly fly (grey belly fly) (Grey belly fly), Gasterophilus intestinalis (Gasterophilus intestinalis) (horse bot), Gracillia persea, Haematobia irritani (Haematobia irrita) (fly), Black fly species (Hymenea spp.) (root maggot) (root fly), Musca (cabbage fly), Musca fly (seedling fly), Musca fly (leaf fly), Musca fly (cabbage fly) (fly), Musca fly (leaf fly), Musca fly (cabbage fly (leaf fly) (fly), Musca fly (leaf fly) (fly, cabbage fly (leaf fly) (fly), Musca fly (leaf fly) (fly), Musca fly (leaf fly) (fly) and Musca fly (leaf fly) (fly) of Musca fly), Musca fly (leaf, Musca fly) (fly) of Musca fly), Musca fly (fly) (fly, Musca fly) (fly, The plant includes, but is not limited to, the species fall houseflies (Musca australis) (face fly), houseflies (Vusca domestica) (house fly), sheep houseflies (oesteurs ovis) (sheep nose fly (sheet boot fly)), european stem flies (ostrinia fructicosa) (carrot rust fly (carrotr fly)), cherry fruit flies (rhagopetis cerasi) (cherry fruit fly)), apple fruit flies (rhapontella pomonella) (apple maggot)), red mud fly (Sitodiplosis mossambucus) (cattle yellow fly (stable fly)), and cattle fly (stable fly)).
Hemiptera (Hemiptera) (stinkbug): apolygus lucorum (Acrosteronum hieron) (green stink bug), Oryza sativa (Blissus leucopterus) (long stink bug), Oryza sativa (Caloris norvegicus) (potato stink bug), Tropical stink bug (Cimex hemipterus) (tropical stink), stinkbug (Cimex leucopterus) (bed bug), Daghertus fasciatus, Dichelops furcatus, Oryza sativa (Eucotton stainer), Edestabunda (Oryza sativa), Oryza sativa (Lepidorum), Oryza sativa (Oryza sativa) and Oryza sativa (Oryza sativa) by (Oryza sativa) and/or Oryza sativa (Oryza sativa) for treating plant (Oryza sativa) and/Oryza sativa (Oryza sativa) for treating plant, Lygus hesperus (Lygus hesperus) (western tarnished plant bug), hibiscus syriacus linnaeus (macrocytoericcus hirsutus), neuroolpus longirostris, rice green bugs (Nezara viridula) (southern green stink bug), Lygus planterum (phytolocoris spp.) (Lygus), california planterus (phytoorius californicus), phytoorius relatus, piezocoritus guilidingdinggi, tetrad bugs (podocarpus utilis linus) (folulated plant bug), psycaninum vaccicola, pseudostellaria persica, scorpio corina and trypanosoma (trypanosoma) seed (nose cone).
Homoptera (Homoptera) (aphid, scale, whitefly, leafhopper): piper pisum (Acrythosiphopkinsum) (pea aphid)), Coccinum species (Adelges spp.) (adelgids), Beeuglena brassicae (Aleurodes proteella) (Beeuglena cabbage whitefly), Aleurodicus disperses (Aleurodicus disperses), Aleurothrix striatus (Aleurothrix luteus) (gloomy whitley), Begoniothyria albonensis species (Aluaspis spp.) (Aluraceae biguella), Pectinatus species (Aphrophola sp.) (Aphrophophora spp.) (leafhopper), Rhodococcus rhododendron (Aoniella natura), Begoniothrix gloeosporioides (Begonioth), Begoniothrix gloeosporus (Begoniothrix), Begoniothrix aphid (Begoniothrix), Begoniothrix) aphid (Begoniothrix), Begoniothrix sp (Begoniothrix) and Begoniothrix aphid (Begoniothrix) Aphis (Begonioth), Begonioth (Aphis) Aphis sp), Begonioth (Begonia), Begonioth (Aphis sp), Begonioth (Begonioth) Aphis sp), Begonia), Begonioth (Begonia), Begoniothrix) and Begoniothrix) species (Begoniothrix) of Aphis, Begoniothrix, Aphis, Asparagus tubular aphid (Brachyryyncria asparagi) (Asparagus aphid), Brevennia rehi, cabbage aphid (Brevicornus brassicae) (cabbage aphid), Lecanicillium species (Ceroplastes spp.) (scale), Ceriporiococcus rubens (Ceroplastes rubens) (red wax scale), Cestrum species (Chionastis spp.) (Iceltica), Lecanicillium species (Chrysomophagus spp.) (scale), Ceriporiococcus species (Coccus spp.) (scale), apple pink aphid (Dysapphigenia plantaginea) (sysplex aphid), Phyllopsis viridis (apple aphid) and Lecanicola (apple aphid) plant (apple aphid), Phyllospora major (apple aphid), Phyllospora (apple aphid) and Lecanicola (apple aphid), Phyllospora grandis (apple aphid), Phyllophora gossypium (apple aphid), Leonicola (apple aphid (apple), and Leonicola (apple aphid), Phyllophora variety (apple aphid) and Leonicola (apple aphid) of Leonicola (apple aphid (apple), Leonicola (apple aphid), and leaf, apple aphid (apple), and leaf, leaf strain (apple stem) (maize) plant, leaf strain (apple stem, leaf, Leaf of the species Mylopharyngodium (Macrosiphum grandium) (English grandis)), Long pipe aphid (Macrosiphum rosae) (Rose aphid (rose aphid)), four-leaf hopper (Macrosteles quadratus) (purple leaf hopper (ash leaf hopper)), Mahanarva frimbiola, Meopodium diricum (wheat germ) aphid (rose aphid), Midis Longicornis, peach aphid (Myzus persicae) (peach aphid (green apple aphid)), Nephophylum spruce (Nephotettix spreng) (leaf hopper), Nephotettix cinctix (green leaf hopper), Phosphaera (brown apple aphid) (Phosphaera), Phosphaera (brown apple aphid) (leaf hopper), Phosphaera (leaf hopper), Phosphaericoides) (leaf hopper) (leaf hopper), leaf hopper (leaf hopper) (leaf hopper (leaf), leaf hopper (leaf hopper (leaf hopper) and leaf hopper (leaf hopper) (leaf hopper (leaf hopper) leaf, leaf hopper (leaf hopper) Pygeum sp (mealybugs), pygeus sp (mealybugs), begecky sp (Pseudococcus spp), mealybugs (Pseudococcus brcvps) (pink apple), pernicia pelyridis (quadrspididatus) (saint josephse), pygecky sp (Rhapalosiphum sp.) (aphid), corn leaf aphid (rhaalophilus maida) (corn aphid), corn leaf aphid (bitter orange apple tree), red apple wax apple tree (white apple, Whitefly species (Trialeurodes spp.) (whitefly), greenhouse whitefly (Trialeurodes vaporariorum) (greenhouses whitefly), brown wing whitefly (Trialeurodes abutiloneus) (bandtwing whitefly), cupula species (Unaspis spp.) (scale), arrowhead (Unaspis yanonensis) (arrowhead scale), and Zulia entreriana.
Hymenoptera (Hymenoptera) (ants, wasps and bees): incised leaf ant species (Acrommerx spp.), Sinkiang leaf bees (Athalia rosae), leaf ant species (Atta spp.), Ieafcutting ants, Black ant species (Camponus spp.), wooden ants (carpenter ant), pine leaf bee species (Diprion spp.), leaf bees (sawfly), Formica spp. (Formica spp.), Argentina argentea (Iridogyrmex pollicis) (Argentintinentant), Coccinum subspecies (Monorium spp.), little termites (Monoformium nigrum) (littlet lake ant), Japanese termites (Pharmanye Solenopsis), New pine leaf bee species (Neomerium spp.), family bee species (Meliotica spp.), family bee species (Melisseria meleagle bee), genus Melissa (Melisseria meleagiensis (Solomon), and species of Melissa bee (Solomon spp.) (Polionus spp.), Quadrature, Melissus spp. (Solomone spp.) (Solidanus spp.), and the like), and the species of Melisseria meldonsis (Solomonas, Wasp species (vespela spp.) (yellow jack) and trichogramma species (Xylocopa spp.) (carpenter bee).
Isoptera (Isoptera) (termites): coptotermes spp, Coptotermes curcus, Coptotermes flavus, Coptotermes formosanus, Coptotermes spp, Coptotermes formosanus, Coptotermes spp, Coptotermes formosanus, Coptotermes formotermes spp, Heterotermes spp, Coptotermes formotermes formosanus, Coptotermes formosanus spp, Coptotermes formosanus spp, Coptotermes formosanus spp, Coptotermes formosanus spp, Coptotermes, Reticulitermes banyulensis, Spodoptera grassland (Reticulitermes grassei), Reticulitermes flavipes (Reticulitermes flavipes) (eastern soil-dwelling termites), Reticulitermes flavipes (Reticulitermes hagenii), West Scleropectium (Reticulitermes heperus) (West soil-dwelling termites), Moraxeticles sanguineus (Reticulitermes santonensis), Norterex benthamoides (Reticulitermes speratus), Reticulitermes nigripes (Reticulitermes tibialis), Reticulitermes virginicus (Reticulitermes virginicus), Reticulitermes formosanus species (Schedorthes spp.) and Zootes spp (Zooter termite spp.).
Lepidoptera (Lepidoptera) (moths and butterflies): achoea janata, Trichosporon species (Adoxophyceae spp.), Trichosta gossypii (Adoxophyceae orana), Gekko sp (Agrotis spp.), cutworm ((Agrotis ipsilon) (Black cutter), Trichosta gossypii (Alabama argillacea) (Cotton leaf worm), Amorbia cuneata (Amomum cubensis), Amorbia cuneata, Amylosis trastuella (Na orange) Teng, Anacoptida, Spodoptera fortunei (Na orange), Anacoptids degelata, Spodoptera cuneata (Anarctia lineata) (peach twigs borrer), Athiophylla (Anomyia sanguinea), Trichosta (Boomula japonica) (Boyloptera), Trichosta niponica (Boyloptera), Spodoptera (Ostrinia), Spodoptera (Boyloptera), Spodoptera fructicola (Boyloides kura), Spodoptera (Boyloptera) variety (Boyloptera), Spodopterocarpus (Boyloptera), Spodoptera (Boyloptera) and Boylophyta (Boylopterocarpus (Boylophysa) variety (Boylophysa) including Boylophysa, Spodopterocarpus (Boylophysa) and Boylophysa (Boylophysa) can, The species of the genus Spodoptera (Caloptilia spp.) (Spodoptera exigua), Capua reticulana, peach fruit moth (Carposina niponensis) (peach fruit moth)), Bombycis (Chilo spp.), mango lateral-thread Philippine moth (Chuumetia transversa) (mango shoot front borner), rose leaf roller (Choristeura rosaria) (oblitera rosea) (oblitera), noctuid barrel (noctuid roller), Spodoptera species (Chrysodexis p.), Ostrinia punctata (Cnaphaloceras medialis) (Spodoptera grasses (Spodoptera)), Spodoptera litura (Spodoptera), Coprinus litura (apple leaf moth) (apple moth (Cypress), Spirochaeta (Spirochaeta), Plutella xylostella (Spirocha), Spirochalia xylostella), Spirochalia striata (Conemonorhala), Spirochalia xylostella (Spodoptera), Spirochalia xylostella (Sporina), Spirochada (Sporina), Spirocha (Sporina), Sporina (Sporidina (Sporina), Sporina) and Sporina) species (Sporina) of the family, Sporina (Sporina) and Sporina (Sporina) in the family, Sporina (Sporina) of the family, Sporina (Sporina) and Sporina (Sp, the species Darna diducta, Diaphania sp (Diaphania spp.) (stem borer)), borer sp (Diaphania spp.) (stem borer (staged borer)), borer (Diaphania saccharalis) (sungar borer), southwestern corn stalk (Diaphania grandiflora) (southwestern corn borer), diamond-back seed (eared diamond-back) eared (eared diamond-back), cotton bollworm (eared bollworm), and diamond-back (earia insulata) (egyptiana boreworm), diamond-back (eared diamond-back) (roughh northern pink bollworm), dynastigma (apple stem borer), ostrinia (ostrinia), ostrinia nubila (ostrinia nubila), ostrinia nubilalis (ostrinia nubilalis), ostrinia nubilalis) (ostrinia nubilalis), ostrinia nubilalis (ostrinia nubilalis) (ostrinia nubila nubilalis), ostrinia nubilalis (ostrinia nubilalis), ostrinia nubilalis) (ostrinia nubilalis (ostrinia nubila nubilalis) (ostrinia nubilalis), ostrinia nubilalis (ostrinia nubila nubilalis), ostrinia nubila nubilalis (ostrinia nubilalis), ostrinia nubilalis (ostrinia nubilalis, Noctuid (epiotia aporema), scolyptera bananas (eriodictyon x) (banana skipper), euglenopsis lucida (Eupoecilia ambiguella) (grape berry moth (grape berry moth)), Euxoa auricularia (Euxoa auricularis) (army cutworm), cutworm (ferula sp.) (cutworm), hornworm (gorworm sp.) (moth), oriental moth (grapholitta molesta) (peach (apricot) seed heart worm (original fruit moth)), borer (moth) (soybean leaf moth (cabbage leaf moth)), budworm sp.) (Helicoverpa sp.) (Helicoverpa sp.)), cotton bollworm (corn earworm) (Helicoverpa punctifera), Helicoverpa punctifera (Helicoverpa punctifera) (Helicosa (Helicoverpa sp.)), Helicoverpa sp.) (Helicover, Tomato moth (Keifera lycopersicella) (tomato pinum), white-fin webworm (Leucinodes orbornata) of Solanum, egg plant fruit moth (egg plant fruit borrelia), leaf miner (Leucoptera malinella), the species Plutella xylostella (Lithocollectis spp.), grape leaf moth (Lobesia borrelia) (grape fruit mot), the species Loxagrus (Loxagrus spp.), the species Laurella punctata (Laurella punctata), the species Laurella cerifera (Loxagrus alburena), the species Laurella punctata (Bean white-leaf diculus (Bean) of Leguminosae), the species Lymantria (Lymantria disparis) (grape fruit bud), the species Lymantria dispar) (gypsylla), the species (Lyonetia punctifera), the species Lyonella (apple leaf moth (apple leaf miner), the oil bag (cabbage), the species (cabbage moth) (cabbage leaf borer), the species (leaf moth (Lymantria), the species (Lyonetia punctifera), the species (Lyoneura) of Plutella (Plutella), the species (Plutella) of Plutella (Plutella), the species (Plutella) of Spinacea brueckea fructia (Spinacea), the species of Spinacea (Spodophylla) of Plutella (Spinacea), the species of Spinacea (Spinea), the genus (Spinacea) of Spinacea (Spinaceus), Winter loopers (Operphthora briata) (winter moth)), European corn borer (Ostrinia nubilalis) (European corn borer (European corn borner)), Oxydia vesula, Ostrinia fructicola (Pandemia cerosa) (common grape leaf moth (common currant torax)), apple leaf moth (Pandemia hepiali) (brown apple pitridix), African damascena (Papilio demodula), Red wheat moth (Pectinophora gossypiella) (red bell (pink bollworm)), Arctia species (Peridroma spp.) (Rhizopus), European red tiger (Peridroma sacchrina) (cabbage caterpillar (cabbage)), European red cabbage looper (Peripleria punctatus), European red cabbage moth (cabbage caterpillar), European red cabbage caterpillar (Peripleria spodoptera), European red cabbage caterpillar (cabbage caterpillar), European red cabbage caterpillar (cabbage caterpillar), European cabbage caterpillar (cabbage caterpillar), cabbage caterpillar (cabbage caterpillar) (cabbage caterpillar variety of the species (cabbage caterpillar), cabbage caterpillar (cabbage caterpillar) of the species (cabbage caterpillar, cabbage caterpillar (cabbage caterpillar), cabbage caterpillar (cabbage caterpillar ) of the species of, Cabbage moth (Plutella xylostella) (diamondback moth), grape berry moth (polychrosia virosa) (grapple berry mountain moth), orange fruit moth (Prays endocarps), olive moth (prasys oleae) (olive moth), armyworm species (pseudotales spp.) (noctuid), pseudolitea unipicta (marcescens), soybean looper (pseudolitea includens) (soybe looper), looper (raphanus nu), tryporyza incertulas (scirphaga incertulas), stem borer (Sesamia fischeri), stem moth (Sesamia infusoriana) and Spirospongia armyworm (Spodoptera), cabbage looper (Spirochaetes), cabbage looper (Spirocha spongiosa), cabbage looper (Spodoptera spongiosa), cabbage looper (Spodopterocarpus niponensis) (Spodoptera spongiosa), cabbage looper (Spodopterocarpus niponaria), cabbage looper (Spodopterocarpus nipona), cabbage looper) (Spodoptera), Spodopterocarpus (Spodoptera), Spodoptera) moth (Spodopterocarpus (Spodoptera), Spodoptera) and Spodopterocarpus (Spodopterocarpa) are) species (Spodopterocarpus (Spodopterocarpa) including Spodoptera) and Spodoptera) including Spodopterocarpus (Spodoptera) and Spodoptera) including Spodo, Southern Spodoptera oridania (southern armyworm), athetosis species (synanthondon spp.) (root borer), Therla basilides, Thermia gemmatalis, Chlamydomonas (tienola bisselella) (webbings moth.), Trichoplusia ni (Trichoplusia ni) (camera bbeller), Tolyta domestica (Tuts absoluta), Nematoda species (Yponomeuta spp.), Coffeta (Zeuzeracow corn), and Zeuzera pyrina (Pleurotus parviensis).
Mallophaga ((Mallophaga) feather louse (chewing lice)): sheep feather louse (Bovicola ovis) (sheet biting louse), turkey short horn feather louse (chicken body louse), and chicken feather louse (Menopon gallina) (common henhouse).
Orthoptera (Orthoptera) (grasshopper, locust and cricket): arana nigra (anacrus simplex) (Mormon horns (Mormon cricket)), mole cricket (Gryllotalpidae) (mole cricket)), eastern asia migratory locust (Locusta migratoria), grasshopper species (Melanoplus spp.) (grasshopper), acephalus wing slender thorns (Microcentrum rethreshold) (angular wing broad katydid)), pterophyces species (pterophyces spp.) (pterophyces sp.) (grasshopper), steleophaga egr, pterygrasus furcifera (scudderis) (harlequin bushy bush (fork tailed bustydidid)), and tuberous ridge (vani.
Phthiraptera (Phthiraptera) (sucking lice): the blood sucking lice species (haemattopinus spp.) (cattle and pig lice), sheep jaw lice (sheep lice), head lice (pedigree capitis) (body lice), human body lice (pedigree humanus (body lice) and crab lice (crab lice)).
Siphonaptera (daphnaptera) (fleas): ctenocephalides canis (dog flea), Ctenocephalides felis (cat flea) and human flea (Pulex irutans) (human flea).
Thysanoptera (thrips): frankliniella fusca (Frankliniella fusca) (tobaco third), Frankliniella occidentalis (western flower) Frankliniella hultrias (western flower), Frankliniella shultzii (Frankliniella williamsii) (corn Thrips), Frankliniella glasshouse Thrips (IIelothrips hamoralidis) (greenhous third), Riphisprothrips cruentus, Scirpus sp (Sciroththrips spp), Platycodon grandiflorum (Scirthricirris) (citrus trough), Frankliniella tabacum (Scirthrips spp), Talothriparia (yellow Thrips spp), and Throughthrips (Thripus spp).
Thysanoptera (Thysanura) (bristletail): chlamydomonas species (Lepisma spp.) (silverfish) and locusta species (Thermobia spp.) (locusta spp.).
From the order of Acarina (Acarina) (mites (mite) and cicadas (tick)): woodbee scutellariae (acarapis woodi) (parasitic mites in the trachea of bees), dermatophagoides farinae (Acarus spp.), dermatophagoides farinae (food mites), Acarus macrorhizus (Acarus sriro) (corn mite (grain mite)), mangifera gemini (Aceria mangifera) (mango bud mite), acanthophyrus stictus (Acarus spp.), acanthophycus solani (acanthophyrus sp.), acanthophysalis lycopersici (acanthophyrus sp.), tomaticus setosum (tomatophysus) tomatin (tomatophyceae), acanthophycus purpureus (acanthophyceae), acanthophyrus stictus (acanthophyceae) (apple pythium sp.), procumbens (acanthophyrus sp.), procumbens (mangiferus sp.), rhipifera (mangiferus sp.), rhynchopus sp.), euonymus (bracteus sp.), rhynchopus sp.), euonymus (mangiferus sp.), and mangiferus sp (mangiferus sp.), euonymus sp (mangiferus sp.), euonymus sp (mangiferus sp.), euonymus sp (mangiferus sp.), euonymus sp (mangiferus sp.), euonymus, House dust mite (Dermatophagoides pteronyssinus) (house dust mite), Tetranychus sp (Eotetranus spp.), hornbeam Tetranychus carpesii (Eotetranthus carpini (yellow spider mite), Tetranychus sp.), Gephyrus sp (Epithromyces sp.), Gephylus sp (Eriophenous spp.), hard tick sp (I.D.; es sp.), ticks (tick), Tetranychus sp (Notederus sp.), Microphyrus sp.), Microphycus sp. sp.gracilis (Notederus sp.), Microphycus sp.Olidonensis (Oligonurus sp.), Calycophycus (Ochrophycus sp.), coffee mites (Ocigonurus sp.), Tetranycus rue (Ocygorum sp.), Calmetrycus (Ochropterus), Tetranychus (Ochronus sp.), Tetranychus urticae (Ochrotus sp.), Tetranychus (Phomophus), Tetranychus urticae (Tetranychus sp.), red spider (Tetranychus urticae) (Phoenii)) and Tetranychus urticae (Tetranychus (Tetranyx), Tetranyx (Tetranychus sp.), red), Tetranyi (Tetranychus (Tetranyx) and Tetranyi (Tetranychus) and Tetranyx (Tetranyx) or Tetranychus (Tetranyx (Tetranychus (Tetranyx) or Tetranyx (Tetranyx) or P. sp.), red mites (Tetranychus (Tetranyx) to be), or Tetranyx) to be) to (, Rhizomorpha species (rhizomorph spp.) (root mite (bulb mite)), Sarcoptes scabies (Sarcoptes scabies) (itch mite), coronaria avocado (tetragonophys perseafarae), Tetranychus species (Tetranychus spp.), Tetranychus urticae (Tetranychus urticae) (twospoked spider mite)) and Varroa destructor (Varroa destructor) (honey bee mite).
Nematoda (nematodes): the species Aphelenchoides (Aphelenchoides spp.) (bud and leaf and pine wood nematodes (bud and leaf & pine wood nematodes)), the species nematodiasis (Belonolaevis spp.) (sting nematodes), the species Cyclotella minor (Criconella spp.) (ring nematodes), the species Dirofilaria immitis (dog heartword), the species Ditylenchus spp. (stem and bulb nematodes), the species Trichophythora (Heterodera spp.) (Cytospora spp.), the species Heterocladia (Heterocladia zeae) (maize nematodides), the species Melilodinia spp. (Hichlamyella spp.) (Melilotus spp.)), the species Heterocladospora spp.) (Melilotus spp.)), the species Melilotus spp.) (Melilotus spp.)), the species (Melilotus spp.) (, The species of the genus Rapholus (Rapholus spp.) (Burrowing nematode) and the species of the Leptochloa (Rotylenchus reniformis) (kidney-shaped nematode).
General class (general classes of insects): white pine worm (Scutigerella immaculata).
Particularly, the composition has good control effect on peach aphids, diamond back moths, armyworms and tetranychus cinnabarinus under lower dosage.
Owing to their positive properties, the abovementioned compounds can be used advantageously for protecting crops, domestic animals and breeding animals of agricultural and horticultural importance, as well as the environment in which humans are often exposed, against harmful germs, pests and mites.
The amount of the compound used to achieve the desired effect will vary depending on factors such as the compound used, the crop to be protected, the type of pest, the extent of infection, the climatic conditions, the method of application, and the dosage form employed.
A dose of 10g to 5 kg of compound per hectare provides adequate control.
The invention also discloses a sterilization, disinsection and acaricidal composition which takes the compound shown in the general formula I as an active component. The weight percentage of the active components in the composition for killing bacteria, insects and mites is 0.1-99%. The composition also comprises an agriculturally, forestry and hygienically acceptable carrier.
The compositions of the present invention may be administered in the form of a formulation. The compounds of formula I as active ingredients are dissolved or dispersed in carriers or formulated to be more easily dispersible for bactericidal, insecticidal use. For example: the chemical preparations can be prepared into wettable powder, oil suspension, water suspension, aqueous emulsion, aqueous solution or missible oil and the like. In these compositions, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant may be added.
The technical scheme of the invention also comprises a method for preventing and controlling germs, pests and mites, which comprises the following steps: the effective amount of the bactericidal, insecticidal and acaricidal composition is applied to the pathogenic bacteria, the pests and the mites or the growth medium thereof. Preferably, an effective amount of 10 to 1000 grams per hectare is generally selected, with an effective amount of 20 to 500 grams per hectare being preferred.
For certain applications, for example in agriculture, one or more other fungicides, insecticides, acaricides, herbicides, plant growth regulators or fertilizers and the like can be added to the fungicidal, insecticidal and acaricidal compositions of the present invention, whereby additional advantages and effects can be produced.
The compound has broad-spectrum bactericidal, insecticidal and acaricidal activity, has excellent control effects on diamondback moth, armyworm, aphid, carmine spider mite and the like, particularly has better control effects on the aphid and the carmine spider mite, also has excellent control effects on cucumber downy mildew, corn rust, wheat powdery mildew, rice blast and anthracnose, and can obtain good effects at very low dosage. The compound of the invention also has the characteristics of simple preparation method and the like.
It should be understood that various changes and modifications may be made within the scope of the present invention as defined by the claims.
Detailed Description
The following specific examples are intended to further illustrate the invention, but the invention is in no way limited to these examples (all materials are commercially available unless otherwise indicated).
Synthetic examples
Example 1: preparation of intermediate 4, 6-dichloropyrimidine-5-carbaldehyde oxime
Figure BDA0000733339380000581
6.75g (0.10mol) of hydroxylamine hydrochloride were added in portions to a solution of 17.70g (0.10mol) of 4, 6-dichloro-5-formylpyrimidine in 100mL of N, N-dimethylformamide with stirring at room temperature, and stirring was continued for 2 to 3 hours after completion of the addition. Then slowly heating to 50-60 deg.C, stirring and reacting for 5-7 hours, after TLC monitoring reaction is finished, pouring the reaction liquid into 50mL water, extracting the water phase with (3X 50mL) ethyl acetate, drying with anhydrous magnesium sulfate, filtering, and desolventizing. The residue was dissolved in 50ml of ethyl acetate, left overnight and filtered with suction to give 16.32g of a pale yellow solid. Yield 85.0%, melting point 224.5 ℃.
Example 2: preparation of intermediate 4, 6-dichloropyrimidine-5-aldehyde-O-methyloxime
Figure BDA0000733339380000582
8.35g (0.10mol) of methoxyamine hydrochloride are added in portions to a solution of 17.70g (0.10mol) of 4, 6-dichloro-5-formylpyrimidine in 100mL of N, N-dimethylformamide with stirring at room temperature, and stirring is continued for 2 to 3 hours after the addition is completed. Then slowly heating to 50-60 deg.C, stirring and reacting for 5-7 hours, after TLC monitoring reaction is finished, pouring the reaction liquid into 50mL water, extracting the water phase with (3X 50mL) ethyl acetate, drying with anhydrous magnesium sulfate, filtering, and desolventizing. The residue was dissolved in 50ml of ethyl acetate, left overnight and filtered with suction to give 17.10g of a pale yellow solid. Yield 83.0%, melting point 211.9 ℃.
Example 3: preparation of intermediate 4, 6-dichloropyrimidine-5-aldehyde-O-glyoxime
Figure BDA0000733339380000591
9.75g (0.10mol) of ethoxyamine hydrochloride are added in portions to a solution of 17.70g (0.10mol) of 4, 6-dichloro-5-formylpyrimidine in 100mL of N, N-dimethylformamide with stirring at room temperature, and stirring is continued for 2 to 3 hours after the addition is completed. Then slowly heating to 50-60 deg.C, stirring and reacting for 5-7 hours, after TLC monitoring reaction is finished, pouring the reaction liquid into 50mL water, extracting the water phase with (3X 50mL) ethyl acetate, drying with anhydrous magnesium sulfate, filtering, and desolventizing. The residue was dissolved in 50ml of ethyl acetate, left overnight and filtered with suction to give 17.93g of a pale yellow solid. The yield thereof was found to be 81.5%.
Example 4: preparation of intermediate 2- (4- (5-trifluoromethylpyridine-2-oxy) phenyl) ethylamine
1) Preparation of 2- (4- (5- (trifluoromethyl) pyridin-2-yloxy) phenyl) acetonitrile
Figure BDA0000733339380000592
18.15g (0.1mol) of 2-chloro-5-trifluoromethylpyridine and 15.96g (0.12mol) of p-hydroxyphenylacetonitrile are added to 200ml of butanone, 27.60g (0.2mol) of potassium carbonate are added, the mixture is heated to reflux with stirring, the reaction is carried out for 4 to 10 hours, after the completion of the TLC monitoring reaction, the solvent is evaporated under reduced pressure, 300ml of ethyl acetate is added for extraction, the organic phase is washed successively with 5% aqueous sodium hydroxide solution and 50ml of saturated saline solution each, the solvent is removed under reduced pressure, and the residue is subjected to column chromatography (eluent is ethyl acetate and petroleum ether (boiling range 60 to 90 ℃ C.) at a volume ratio of 1:5) to obtain 22.50g of a white solid, the yield is 81%, and the melting point is 48.
2) Preparation of 2- (4- (5-trifluoromethylpyridine-2-oxy) phenyl) ethylamine
Figure BDA0000733339380000593
A mixture of 2.78g (0.01mol) of 2- (4- (5-trifluoromethylpyridine-2-oxyl) phenyl) acetonitrile, Raney nickel (1.0g), 10ml of 25 percent ammonia water and 50ml of ethanol is stirred and reacted for 3 to 15 hours at room temperature in a hydrogen atmosphere, after TLC monitoring reaction is finished, the Raney nickel is filtered, the solvent is evaporated under reduced pressure to obtain viscous liquid, and after cooling, 2.20g of white solid is obtained, the yield is 78 percent, and the melting point is 82 to 83 ℃.
Example 5: preparation of intermediate 2- (4- (6-chloro-2-methylpyrimidin-4-oxy) phenyl) ethylamine hydrochloride
1) Preparation of N-Boc-4-hydroxyphenylethylamine
Figure BDA0000733339380000594
Dissolving 11.3g (0.1mol) of 4-hydroxy phenethylamine in 80ml of tetrahydrofuran, sequentially adding 10.08g (0.12mol) of sodium bicarbonate and 50ml of water, dropwise adding 21.80g (0.1mol) of di-tert-butyl dicarbonate under stirring at room temperature, continuing to react for 4-10 hours, after TLC monitoring reaction is finished, evaporating under reduced pressure to remove the solvent, adding (3X 50ml) ethyl acetate for extraction, washing an organic phase with 50ml of saturated saline solution, performing desolvation under reduced pressure, and performing column chromatography on residues (eluent is ethyl acetate and petroleum ether (boiling range is 60-90 ℃) at a volume ratio of 1:4) to obtain 17.15g of white solid, wherein the yield is 81%, and the melting point is 48-49 ℃.
2) Preparation of N-Boc-2- (4- (6-chloro-2-methylpyrimidin-4-oxy) phenyl) ethylamine
Figure BDA0000733339380000601
Adding 2.37g (0.01mol) of N-Boc-4-hydroxyphenylethylamine and 1.63g (0.01mol) of 2-methyl-4, 6-dichloropyrimidine into 50ml of butanone, then adding 2.76g (0.02mol) of potassium carbonate, heating to reflux under stirring, reacting for 4-10 hours, after TLC monitoring reaction is finished, evaporating under reduced pressure to remove the solvent, adding (3X 50ml) of ethyl acetate for extraction, washing an organic phase by 50ml of saturated saline, performing desolvation under reduced pressure, and performing column chromatography on a residue (eluent is ethyl acetate and petroleum ether (boiling range is 60-90 ℃) at a volume ratio of 1:5) to obtain 2.87g of a white solid, wherein the yield is 79.0%, and the melting point is 105-.
3) Preparation of 2- (4- (6-chloro-2-methylpyrimidin-4-oxy) phenyl) ethylamine hydrochloride
Figure BDA0000733339380000602
Adding 3.64g (0.01mol) of N-Boc-2- (4- (6-chloro-2-methylpyrimidine-4-oxyl) phenyl) ethylamine into 50ml of ethyl acetate, dropwise adding 15ml of concentrated hydrochloric acid while stirring at room temperature to dissolve solids, continuously stirring for 4-5 hours to precipitate a large amount of solids, performing suction filtration, and washing a filter cake with 10ml of ethyl acetate to obtain 2.55g of white solids, wherein the yield is 85.0 percent, and the melting point is 224-.
Example 6: preparation of Compound 489
Figure BDA0000733339380000603
2.20g (0.01mol) of 4, 6-dichloropyrimidine-5-aldehyde-O-glyoxime and 2.93g (0.01mol) of 4- (4- (2-ethylamino) phenoxy) -3-fluorobenzonitrile are added to 30ml of N, N-dimethylformamide, 2.76g (0.02mol) of potassium carbonate are added, the mixture is heated to reflux and reacted for 3 to 10 hours, after the TLC monitoring reaction is finished, the solvent is evaporated under reduced pressure, 3X 50ml of ethyl acetate is added for extraction, the organic phase is washed with 50ml of saturated saline, desolventization under reduced pressure is carried out, and column chromatography of the residue is carried out (eluent is ethyl acetate and petroleum ether (boiling range: 60 ℃ C.) at a volume ratio of 1:3) to obtain 3.60g of white solid, the yield is 82.0%, and the melting point is 97.8 ℃.
Example 7: preparation of compound 10283
Figure BDA0000733339380000604
1.92g (0.01mol) of 4, 6-dichloropyrimidine-5-carbaldehyde oxime and 2.82g (0.01mol) of 2- (4- (5-trifluoromethylpyridine-2-oxyl) phenyl) ethylamine were added to 30ml of N, N-dimethylformamide, 2.76g (0.02mol) of potassium carbonate were added, the mixture was heated to reflux and reacted for 3 to 10 hours, after the completion of the reaction monitored by TLC, the solvent was distilled off under reduced pressure, ethyl acetate (3X 50ml) was added for extraction, the organic phase was washed with 50ml of saturated saline, desolventization under reduced pressure was carried out, and column chromatography of the residue (eluent ethyl acetate and petroleum ether (boiling range: 60 to 90 ℃ C.) at a volume ratio of 1:3) gave 3.70g of a white solid, yield 84.5%, and melting point 208.0 ℃.
Example 8: preparation of compound 10306
Figure BDA0000733339380000611
1.92g (0.01mol) of 4, 6-dichloropyrimidine-5-formaldoxime and 3.17g (0.01mol) of 2- (4- (3-chloro-5- (trifluoromethyl) pyridin-2-yloxy) phenyl) ethylamine were added to 30ml of N, N-dimethylformamide, 2.76g (0.02mol) of potassium carbonate were added, the mixture was heated to reflux and reacted for 3 to 10 hours, after completion of the reaction monitored by TLC, the solvent was distilled off under reduced pressure, ethyl acetate (3X 50ml) was added for extraction, the organic phase was washed with 50ml of saturated saline, desolventization under reduced pressure, and the residue was subjected to column chromatography (eluent: ethyl acetate and petroleum ether (boiling range: 60 ℃ C. to 90 ℃ C.) in a volume ratio of 1:3) to obtain 3.82g of a white solid, yield 81.0%, melting point 198.0 ℃.
Example 9: preparation of compound 10373
Figure BDA0000733339380000612
Adding 2.06g (0.01mol) of 4, 6-dichloropyrimidine-5-aldehyde-O-methyloxime and 2.82g (0.01mol) of 2- (4- (5-trifluoromethylpyridine-2-oxy) phenyl) ethylamine into 30ml of N, N-dimethylformamide, adding 2.76g (0.02mol) of potassium carbonate, heating to reflux, reacting for 3-10 hours, after TLC monitoring reaction is finished, evaporating the solvent under reduced pressure, adding (3X 50ml) of ethyl acetate for extraction, washing an organic phase by using 50ml of saturated saline, performing reduced pressure desolventization, performing column chromatography on a residue (eluent is ethyl acetate and petroleum ether (boiling range is 60-90 ℃) at a volume ratio of 1:3) to obtain 3.63g of white solid, wherein the yield is 80.5%, and the melting point is 76.6 ℃.
Example 10: preparation of compound 10463
Figure BDA0000733339380000613
2.20g (0.01mol)4, 6-dichloropyrimidine-5-aldehyde-O-glyoxime and 2.82g (0.01mol)2- (4- (5-trifluoromethylpyridine-2-oxy) phenyl) ethylamine were added to 30ml of N, N-dimethylformamide, 2.76g (0.02mol) of potassium carbonate were added, the mixture was heated to reflux and reacted for 3 to 10 hours, after the completion of the TLC monitoring reaction, the solvent was distilled off under reduced pressure, ethyl acetate (3X 50ml) was added for extraction, the organic phase was washed with 50ml of saturated saline, desolventization under reduced pressure was carried out, column chromatography of the residue was carried out (eluent ethyl acetate and petroleum ether (boiling range: 60 ℃ C. -90 ℃ C.), volume ratio was 1:3) to obtain 3.87g of a white oily substance, and yield was 83.1%.
Example 11: preparation of Compound 10643
Figure BDA0000733339380000614
2.06g (0.01mol) of 4, 6-dichloropyrimidine-5-aldehyde-O-methyloxime and 3.17g (0.01mol) of 2- (3-chloro-4- (5- (trifluoromethyl) pyridin-2-yloxy) phenyl) ethylamine were added to 30ml of N, N-dimethylformamide, 2.76g (0.02mol) of potassium carbonate was added, the mixture was heated to reflux and reacted for 3 to 10 hours, after completion of the TLC monitoring reaction, the solvent was distilled off under reduced pressure, ethyl acetate (3X 50ml) was added for extraction, the organic phase was washed with 50ml of saturated saline, and desolventization under reduced pressure was carried out, and column chromatography of the residue was carried out (eluent was ethyl acetate and petroleum ether (boiling range 60-90: 1) at a volume ratio to give 3.91g of a white solid, yield 80.4%, melting point 107.8 ℃.
Example 12: preparation of Compound 14435
Figure BDA0000733339380000621
2.20g (0.01mol) of 4, 6-dichloropyrimidine-5-aldehyde-O-glyoxime and 3.00g (0.01mol) of 2- (4- (6-chloro-2-methylpyrimidine-4-oxy) phenyl) ethylamine were added to 30ml of N, N-dimethylformamide, 2.76g (0.02mol) of potassium carbonate were added, the mixture was heated to reflux and reacted for 3 to 10 hours, after the completion of the reaction monitored by TLC, the solvent was distilled off under reduced pressure, ethyl acetate (3X 50ml) was added for extraction, the organic phase was washed with 50ml of saturated saline, desolventized under reduced pressure, and the residue was subjected to column chromatography (eluent: ethyl acetate and petroleum ether (boiling range: 60 to 90 ℃ C.) at a volume ratio of 1:3) to give 3.81g of a white solid, yield 85.3%, melting point 133.7 ℃.
Example 13: preparation of compound 16329
Figure BDA0000733339380000622
2.20g (0.01mol) of 4, 6-dichloropyrimidine-5-aldehyde-O-glyoxime and 2.68g (0.01mol) of 2- (4- (5-trifluoromethylpyridine-2-oxy) phenyl) methylamine are added into 30ml of N, N-dimethylformamide, 2.76g (0.02mol) of potassium carbonate is added, the mixture is heated to reflux and reacted for 3 to 10 hours, after the TLC monitoring reaction is finished, the solvent is evaporated under reduced pressure, 3X 50ml of ethyl acetate is added for extraction, an organic phase is washed by 50ml of saturated saline, the mixture is desolventized under reduced pressure, and the residue is subjected to column chromatography (eluent is ethyl acetate and petroleum ether (boiling range is 60 to 90 ℃) at the volume ratio of 1:3) to obtain 3.59g of white oily matter with the yield of 79.6%.
Other compounds of formula I may be prepared by the preparation methods provided by the present invention.
Melting Point of some Compounds (melting Point instrument uncorrected) and Nuclear magnetic data: (1HNMR, 300MHz, internal standard TMS, solvent CDCl3) The following were used:
compound 489: the melting point was 97.8 ℃. ppm 1.26(3H, t),2.97(2H, t),3.91(2H, q),4.08(2H, q),6.96(3H, m),7.30(2H, d),7.37(1H, d),7.47(1H, d),8.32(1H, s),8.41(2H, m),8.58(1H, s).
Compound 10306: the melting point was 198.0 ℃. (ppm) 2.98(2H, t),4.03(2H, q),7.19(2H, d),7.36(2H, d),8.07(1H, d),8.26(3H, m),8.50(1H, s),9.30(1H, s).
Compound 10283: the melting point was 208.0 ℃. (ppm) 2.96(2H, t),4.03(2H, q),7.18(3H, m),7.33(2H, d),8.00(1H, m),8.31(3H, m),8.50(1H, s),9.78(1H, s).
Compound 10373: the melting point was 76.6 ℃. (ppm) 2.99(2H, t),3.81(3H, s),3.91(2H, q),7.01(1H, d),7.11(2H, d),7.32(2H, d),7.90(1H, m),8.34(1H, s),8.42(2H, m),8.58(1H, s).
Compound 10463: an oil. ppm 1.25(3H, t),2.98(2H, t),3.93(2H, q),4.08(2H, q),7.00(1H, d),7.10(2H, d),7.30(2H, d),7.90(1H, m),8.33(1H, s),8.43(2H, m),8.59(1H, s).
Compound 10486: the melting point was 77.1 ℃. ppm 1.24(3H, t),2.99(2H, t),3.94(2H, q),4.08(2H, q),7.12(2H, d),7.31(2H, d),7.98(1H, s),8.26(1H, d),8.33(1H, s),8.43(1H, s),8.58(1H, s).
Compound 10643: the melting point was 107.8 ℃. ppm:2.98(2H, t),3.94(2H, q),7.09(1H, d),7.19(2H, m),7.43(1H, m),7.96(1H, m),8.38(3H, m),8.59(1H, s).
Compound 10733: an oil. ppm 1.26(3H, t),2.98(2H, t),3.94(2H, q),4.11(2H, q),7.09(1H, d),7.19(2H, m),7.38(1H, s),7.93(1H, m),8.36(1H, m),8.45(2H, m),8.60(1H, s).
Compound 14435: the melting point was 133.7 ℃. ppm 1.24(3H, t),1.62(3H, s),4.14(2H, q),4.77(2H, t),6.82(1H, s),7.26(2H, d),7.33(2H, d),8.34(1H, s),8.63(1H, s),8.78(1H, s).
Compound 16329: an oil. ppm 1.28(3H, t),4.18(2H, q),4.84(2H, d),7.03(1H, d),7.15(2H, d),7.41(2H, d),7.90(1H, dd),8.35(1H, s),8.42(1H, m),8.64(1H, s),8.82(1H, s).
Compound 16388: an oil. ppm:1.27(3H, t),4.10(2H, q),4.75(2H, d),7.02(1H, d),7.15(2H, d),7.41(2H, d), 7.50(1H, s),8.81(1H, s).
Examples of measurement of biological Activity
EXAMPLE 14 Bactericidal Activity assay
(1) Living body protecting Activity assay
The measurement method is as follows: the living potted plant determination method is adopted, i.e. a sample of the compound to be tested is dissolved by a small amount of solvent (the type of the solvent is acetone, methanol, DMF, etc., and is selected according to the dissolving capacity of the solvent to the sample, and the volume ratio of the solvent amount to the liquid spraying amount is equal to or less than 0.05), and diluted by water containing 0.1 percent of Tween 80 to prepare the liquid to be tested with the required concentration. The solution to be tested is sprayed on diseased host plants (the host plants are standard potted seedlings cultured in a greenhouse) on a crop sprayer, and disease inoculation is carried out after 24 hours. According to the characteristics of diseases, inoculating the disease plants needing temperature and moisture control culture, then culturing in an artificial climate chamber, transferring into a greenhouse for culture after the diseases are infected, and directly inoculating and culturing the disease plants without moisture control culture in the greenhouse. The results of the activity to be protected test are as follows:
the compound disease control effect evaluation is carried out after full disease (usually a week) of the living control of cucumber downy mildew.
In vivo protective activity of part of the compounds:
when the concentration of the liquid medicine is 400ppm, the control effect of the compounds 489, 10306, 10463, 10486, 10643 and the like on cucumber downy mildew is 100 percent, and the control effect of the compounds 14435, 16388 and the like on cucumber downy mildew is 95 percent;
when the concentration of the liquid medicine is 100ppm, the control effect of the compounds 489, 10306, and the like on cucumber downy mildew is 100 percent, and the control effect of the compounds 10463, 16388, and the like on cucumber downy mildew is 90 percent;
when the concentration of the liquid medicine is 25ppm, the control effect of the compound 489 and the like on wheat powdery mildew is 100 percent, and the control effect of the compound 10306 and the like on cucumber downy mildew is 85 percent;
in vivo protective activity against wheat powdery mildew:
when the concentration of the liquid medicine is 400ppm, the control effect of the compounds 10463, 10486, 10643, 16329 and the like on wheat powdery mildew is 100 percent;
in vivo protective activity against corn rust:
when the concentration of the liquid medicine is 400ppm, the control effect of the compounds 10283, 10306, 10373, 10463, 10486, 10643 and the like on the corn rust is 100 percent, the control effect of the compound 16329 and the like on the corn rust is 95 percent, and the control effect of the compound 14435 and the like on the corn rust is 80 percent;
when the concentration of the liquid medicine is 100ppm, the control effect of the compounds 10306, 10373 and the like on the corn rust is 100 percent, the control effect of the compounds 10283 and the like on the corn rust is 90 percent, and the control effect of the compounds 10463, 10486 and the like on the corn rust is 80 percent;
when the concentration of the liquid medicine is 25ppm, the control effect of the compound 10373 on the corn rust is 90 percent, and the control effect of the compound 10486 on the corn rust is 80 percent.
(2) In vitro bactericidal activity assay
The measurement method is as follows: the high-throughput screening method is adopted, i.e. a compound sample to be detected is dissolved by using a proper solvent (the type of the solvent is acetone, methanol, DMF, and the like, and is selected according to the dissolving capacity of the solvent on the sample), and a liquid to be detected with the required concentration is prepared. Under an ultraclean working environment, adding a solution to be detected into micropores of a 96-hole culture plate, adding a pathogen propagule suspension into the micropore, and placing the treated culture plate in a constant-temperature incubator for culture. And (4) after 24 hours, carrying out investigation, visually observing the germination or growth condition of the pathogen propagules during the investigation, and evaluating the bacteriostatic activity of the compound according to the germination or growth condition of the control treatment.
The results of the in vitro bacteriostatic activity (expressed as inhibition) test of some compounds are as follows:
inhibition rate of Pyricularia oryzae:
at a chemical concentration of 25ppm, the inhibition ratio of compound 14435 or the like against rice blast was 80%.
Inhibition rate of anthrax bacteria:
when the concentration of the chemical solution is 400ppm, the inhibition rate of the compound 489 and the like on anthracnose is 95%.
EXAMPLE 15 insecticidal and acaricidal Activity assay
Several insects were tested for insecticidal activity using the compounds of the present invention. The measurement method is as follows:
after dissolving a test compound in a mixed solvent of acetone/methanol (1: 1), the test compound was diluted with water containing 0.1% (wt) Tween 80 to a desired concentration.
The insecticidal activity is determined by taking diamondback moth, armyworm, green peach aphid and tetranychus cinnabarinus as targets and adopting an airrbrush spraying method.
(1) Activity assay for diamondback moth
The determination method comprises the following steps: the cabbage leaves were punched out into a 2 cm-diameter disk by a punch, and the pressure of airbrush spray treatment was 10psi (approximately 0.7 kg/cm)2) Spraying on the front and back sides of each leaf disc, wherein the liquid spraying amount is 0.5 ml. After drying in the shade, 10 test insects of 2 years old are inoculated in each treatment, and the treatment is repeated for 3 times. And (4) after treatment, placing the treated mixture into an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% for culture, investigating the number of the survival insects after 72 hours, and calculating the mortality.
Partial test results for plutella xylostella are as follows:
when the concentration of the liquid medicine is 600ppm, the lethality of the compounds 489, 10283, 10306, 10373, 10463, 10486, 10643 and the like to diamond back moth is 100%;
when the concentration of the drug solution is 100ppm, the lethality of the compounds 489 and 10283 to plutella xylostella is 89% and 80%, respectively.
(2) Determination of the Activity on armyworm:
the determination method comprises the following steps: the corn leaves were cut into 2cm long sections and the airbrush spray treatment pressure was 10psi (approx. 0.7 kg/cm)2) Spraying on the front and back sides of each leaf segment, wherein the liquid spraying amount is 0.5 ml. After drying in the shade, 10 test insects of 2 years old are inoculated in each treatment, and the treatment is repeated for 3 times. And (4) after treatment, placing the treated mixture into an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% for culture, investigating the number of the survival insects after 72 hours, and calculating the mortality.
The results of the partial test on armyworm are as follows:
when the concentration of the liquid medicine is 600ppm, the lethality of the compounds 489, 10283, 10373, 10463, 10486, 10643 and the like to armyworms is 100%;
when the concentration of the liquid medicine is 100ppm, the lethality of the compounds 489, 10463 and 10643 and the like to armyworms is 100%, the lethality of the compounds 10373 and the like to armyworms is 95%, and the lethality of the compounds 10283 and the like to armyworms is 85%;
when the concentration of the chemical solution is 10ppm, the lethality of the compound 489 and the like to armyworms is 88%.
(3) And (3) measuring the activity of the green peach aphids:
the determination method comprises the following steps: a culture dish with the diameter of 6cm is taken, a layer of filter paper is covered on the bottom of the culture dish, and a proper amount of tap water is dripped for moisturizing. And (3) shearing cabbage leaves with proper size (the diameter is about 3cm) and 15-30 heads of aphids from the cabbage plants for culturing the myzus persicae, removing the aphids with the wing aphids and the front sides of the leaves, and placing the leaves in a culture dish with the back sides upward. The airbrush spray treatment was carried out at a pressure of 10psi (approx. 0.7kg/cm2) and a liquid spray volume of 0.5ml, with 3 repetitions of the treatment. And (3) after treatment, placing the treated mixture into an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% for culture, investigating the number of the survival insects after 48 hours, and calculating the mortality.
The results of a part of the tests on myzus persicae are as follows:
when the concentration of the liquid medicine is 600ppm, the lethality of the compounds 489, 10283, 10306, 10373, 10463, 10486, 10643, 16329, 16388 and the like to the myzus persicae is 100 percent;
when the concentration of the liquid medicine is 100ppm, the lethality of the compounds 489, 10283, 10306, 10373, 10463, 10486, 10643, 16388 and the like to the green peach aphids is 100 percent;
when the concentration of the liquid medicine is 10ppm, the lethality of the compounds 489, 10283, 10306, 10463, 10643 and the like to the green peach aphids is 100 percent;
when the concentration of the liquid medicine is 5ppm, the lethality of the compound 10463 and the like to the green peach aphids is 100%.
(4) And (3) measuring tetranychus cinnabarinus:
the determination method comprises the following steps: collecting two bean seedlings of true leaf vegetable, inoculating Tetranychus cinnabarinus, examining the base number, and treating with airrbrush sprayer under 10psi (about 0.7 kg/cm)2) The amount of the sprayed liquid was 0.5 ml. Each treatment was repeated 3 times, and after treatment, the treated mites were placed in a standard observation room, and after 72 hours, the number of live mites was investigated, and the mortality was calculated.
Partial test results on tetranychus cinnabarinus are as follows:
when the concentration of the liquid medicine is 600ppm, the lethality of the compounds 489, 10283, 10373, 10463, 10643 and the like to tetranychus cinnabarinus is 100%;
when the concentration of the liquid medicine is 100ppm, the lethality of the compounds 10283, 10373, 10463, 10643 and the like to tetranychus cinnabarinus is 100%, and the lethality of the compounds 489 and the like to tetranychus cinnabarinus is 98%;
when the concentration of the liquid medicine is 10ppm, the lethality of the compound 10643 to tetranychus cinnabarinus is 100%, and the lethality of the compounds 10283, 10373 and the like to tetranychus cinnabarinus is 98-99%.
In addition, toxicology experimental determination is carried out, and specific results are as follows:
compound 10283 of this patent is administered in half the acute oral Lethal Dose (LD) to male and female rats50)>50mg/kg, acute oral toxicity is low toxicity or poisoning. CK1, CK2(CN103772357A compounds No. 22 and 254) are used for acute oral half-Lethal Dose (LD) of male and female rats50)<50mg/kg, and the acute oral toxicity is high toxicity or virulent.
Figure BDA0000733339380000651

Claims (5)

1. An oxime group-containing pyrimidine compound is characterized in that the structure of the compound is shown as a general formula I-B:
Figure FDA0002661020850000011
in the formula:
R1selected from halogens;
R2selected from hydroxy or C1-C4An alkoxy group;
R3selected from hydrogen;
X1、X2、X3、X4selected from hydrogen;
R6selected from hydrogen;
R7selected from hydrogen;
R9selected from halogen C1-C4An alkyl group;
R10selected from hydrogen or halogen;
a is selected from NH;
or salts of the compounds of the general formula I-B with hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, sorbic acid, malic acid or citric acid.
2. The compound of claim 1, wherein:
in the general formula I-B
R1Selected from chlorine;
R2selected from hydroxy, methoxy or ethoxy;
R3selected from hydrogen;
X1、X4selected from hydrogen; x2、X3Selected from hydrogen;
R6、R7selected from hydrogen, chlorine;
R9is selected from trifluoromethyl;
R10selected from hydrogen or chlorine;
a is selected from NH;
alternatively, the compounds of formula I-B are salts with hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, benzoic acid, phthalic acid, maleic acid, sorbic acid, malic acid, or citric acid.
3. The use of the compound of the general formula I-B or a salt thereof according to claim 1 for the preparation of a fungicide, insecticide, acaricide, or a medicament in the agricultural, forestry or sanitary field.
4. The bactericidal, insecticidal and acaricidal composition is characterized by comprising the following components in parts by weight: contains the compound of the general formula I-B or the salt thereof as claimed in claim 1 as an active component, wherein the weight percentage of the active component in the composition is 0.1-99%.
5. A method for preventing and controlling germs, pests and mites in the agricultural field without treatment purpose is characterized in that: applying an effective amount of the composition of claim 4 to said pathogen, pest mite or growth medium thereof.
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WO2013113719A1 (en) * 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds ii
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WO2013113719A1 (en) * 2012-02-03 2013-08-08 Basf Se Fungicidal pyrimidine compounds ii
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