CN112745297B - Pyrimidine-containing piperidine amine compound and preparation method and application thereof - Google Patents

Pyrimidine-containing piperidine amine compound and preparation method and application thereof Download PDF

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CN112745297B
CN112745297B CN202011175409.9A CN202011175409A CN112745297B CN 112745297 B CN112745297 B CN 112745297B CN 202011175409 A CN202011175409 A CN 202011175409A CN 112745297 B CN112745297 B CN 112745297B
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piperidyl
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CN112745297A (en
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关爱莹
杨金龙
常秀辉
张鹏飞
王军锋
王立增
张俊龙
杨萌
孙庚�
刘长令
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Jiangsu Yangnong Chemical Co Ltd
Shenyang Sinochem Agrochemicals R&D Co Ltd
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Shenyang Sinochem Agrochemicals R&D Co Ltd
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-diazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—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
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Abstract

The invention discloses a piperidine amine compound containing pyrimidine, which has a structure shown as a general formula I: the definition of each substituent group in the formula is shown in the specification. The compound of the invention simultaneously shows good insecticidal and acaricidal activity, and has excellent control effects on diamondback moth, tetranychus cinnabarinus and the like. Meanwhile, the bactericidal composition has broad-spectrum bactericidal activity and has excellent control effects on cucumber downy mildew, wheat powdery mildew, cucumber anthracnose and the like.

Description

Pyrimidine-containing piperidine amine compound and preparation method and application thereof
Technical Field
The invention belongs to the field of agricultural sterilization, disinsection and acaricidal, and particularly relates to a novel piperidine amine compound containing pyrimidine, and a preparation method and application thereof.
Background
Patent DE 4208254 discloses a piperidine amine compound with a general formula shown as the following, and the compound is applied to agricultural sterilization, insecticide, acaricide and the like. Specific compounds CK1, CK2, CK3, CK4, CK5 and CK6 are disclosed, but no specific biological activity is reported.
Figure BDA0002747185910000011
Patent US 20140113915 discloses the following general formula and specific compound CK7 for medical use.
Figure BDA0002747185910000012
However, the piperidine amine compound containing pyrimidine with the structure shown in the general formula I is not reported.
Disclosure of Invention
The invention aims to provide a piperidine amine compound containing pyrimidine, which can control various germs, pests and mites, a preparation method thereof and application of the piperidine amine compound in preparing medicines for preventing and controlling germs and/or pests and mites in agriculture or other fields.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a piperidine amine compound containing pyrimidine, characterized in that: the piperidine amine compound containing pyrimidine is a compound shown as a general formula I;
Figure BDA0002747185910000021
R 1 selected from halogen, cyano, nitro, carboxyl, C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 3 -C 12 Cycloalkyl radical, C 1 -C 12 Alkoxy, halo C 1 -C 12 Alkoxy radical, C 1 -C 12 Alkylthio, halo C 1 -C 12 Alkylthio radical, C 1 -C 12 Alkylsulfinyl radical, C 1 -C 12 Alkylsulfonyl radical, C 2 -C 12 Alkenyl, halo C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, halo C 2 -C 12 Alkynyl, C 3 -C 12 Alkenyloxy, halogeno C 3 -C 12 Alkenyloxy radical, C 3 -C 12 Alkynyloxy, halo C 3 -C 12 Alkynyloxy, C 1 -C 12 Alkylamino radical, di (C) 1 -C 12 Alkyl) amino, C 1 -C 12 Alkylaminocarbonyl, halogeno C 1 -C 12 Alkylaminocarbonyl radical, C 1 -C 12 Alkoxycarbonyl, halo C 1 -C 12 Alkoxycarbonyl group, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl or C 1 -C 2 Alkylthio group C 1 -C 12 An alkyl group;
R 2 selected from halogen, cyano, nitro, amino, carboxyl, formyl, C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxy, halo C 1 -C 12 Alkoxy or acetal groups;
w is selected from hydrogen, halogen, C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 3 -C 8 Cycloalkyl radicals、C 1 -C 12 Alkoxy radical, C 1 -C 12 Alkylthio or C 1 -C 12 An alkylsulfonyl group;
R 3 selected from hydrogen, hydroxy, formyl, C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxy, halo C 1 -C 12 Alkoxy radical, C 3 -C 12 Cycloalkyl radical, C 1 -C 12 Alkylthio radical, C 2 -C 12 Alkenylthio radical, C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, halo C 2 -C 12 Alkenyl, halo C 2 -C 12 Alkynyl, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl, halo C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylthio group C 1 -C 12 Alkyl, halo C 1 -C 12 Alkylthio group C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylsulfinyl, halogeno C 1 -C 12 Alkylsulfinyl radical, C 1 -C 12 Alkylsulfonyl, halo C 1 -C 12 Alkylsulfonyl radical, C 1 -C 12 Alkylaminosulfonyl, di (C) 1 -C 12 Alkyl) aminosulfonyl, C 1 -C 12 Alkylsulfonylaminocarbonyl group, C 1 -C 12 Alkylcarbonylaminosulfonyl radical, C 3 -C 12 Cycloalkyloxycarbonyl radical, C 1 -C 12 Alkylcarbonyl, halo C 1 -C 12 Alkylcarbonyl group, C 1 -C 12 Alkoxycarbonyl, halo C 1 -C 12 Alkoxycarbonyl group, C 1 -C 12 Alkyl carbonyl radical C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxycarbonyl radical C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylaminocarbonyl, di (C) 1 -C 12 Alkyl) aminocarbonyl, C 2 -C 12 Alkenyloxycarbonyl radical, C 2 -C 12 Alkynyloxycarbonyl, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkoxycarbonyl group, C 1 -C 12 Alkylamino thio, di (C) 1 -C 12 Alkyl) aminothio, arylcarbonyl C which is unsubstituted or further substituted by 1 to 5 1 -C 6 Alkyl, arylcarbonyl, aryloxycarbonyl, aryl C 1 -C 6 Alkyloxycarbonyl, aryl C 1 -C 6 Alkyl, aryl carbonyl C 1 -C 6 Alkyl, arylcarbonyl, aryloxycarbonyl, aryl C 1 -C 6 Alkyloxycarbonyl, aryl C 1 -C 6 Alkyl, heteroaryl carbonyl C 1 -C 6 Alkyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroaryl C 1 -C 6 Alkyloxycarbonyl, heteroaryl C 1 -C 6 Alkyl, heteroaryl carbonyl C 1 -C 6 Alkyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heteroaryl C 1 -C 6 Alkyloxycarbonyl, heteroaryl C 1 -C 6 Alkyl, the following groups being halogen, nitro, cyano, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy or halo C 1 -C 6 An alkoxy group;
q is selected from Q 1 、Q 2 、Q 3 、Q 4 、Q 5 、Q 6 A fused ring or a fused heterocyclic ring;
wherein Q is 1 Selected from the group consisting of 1-5R 4 Substituted phenyl, with R 4 At least 1 of them is an electron-withdrawing group; and the benzene ring is not mono-fluorine substituted; and does not comprise the following compounds: 6-ethyl-5-fluoro-N- (1- (2-fluoro-5-methylphenyl) -piperidin-4-yl) pyrimidin-4-amine;
Q 2 selected from the group consisting of 0-4R 4 A substituted pyridyl group; and does not comprise the following compounds:
5-chloro-6-ethyl-N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine; 5-methoxy-6- (methoxymethyl) -N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine;
Q 3 selected from the group consisting of 0-3R 4 A substituted pyrimidinyl group; and Q 3 Not being unsubstituted 2-a pyrimidinyl group; and does not comprise the following compounds: n- (1- (2,6-dimethylpyrimidin-4-yl) piperidin-4-yl) -6-ethyl-5-fluoropyrimidin-4-amine;
Q 4 selected from the group consisting of 0-3R 4 A substituted pyridazinyl group; and does not include the following compounds:
2-cyclopropyl-5-methoxy-6-methyl-N- (1- (pyridazin-3-yl) piperidin-4-yl) pyrimidin-4-amine;
Q 5 selected from the group consisting of 0-3R 4 A substituted pyrazinyl group;
Q 6 selected from the group consisting of 0-2R 4 Substituted s-triazinyl or s-triazinyl;
R 4 selected from halogen, carboxyl, aldehyde group, amino, cyano, nitro, C 1 -C 12 Alkyl, halo C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxy, halo C 1 -C 12 Alkoxy radical, C 3 -C 12 Cycloalkyl radical, C 1 -C 12 Alkylamino, halogeno C 1 -C 12 Alkylamino radical, di (C) 1 -C 12 Alkyl) amino, halo-di (C) 1 -C 12 Alkyl) amino, C (= O) NR 5 R 6 、C 1 -C 12 Alkylcarbonylamino, C 1 -C 12 Alkylthio, halogeno C 1 -C 12 Alkylthio radical, C 2 -C 12 Alkenyl radical, C 2 -C 12 Alkynyl, C 2 -C 12 Alkenyloxy, halogeno C 2 -C 12 Alkenyloxy radical, C 2 -C 12 Alkynyloxy, halo C 2 -C 12 Alkynyloxy, C 1 -C 12 Alkylsulfonyl, halo C 1 -C 12 Alkylsulfonyl radical, C 1 -C 12 Alkylcarbonyl, halo C 1 -C 12 Alkylcarbonyl group, C 1 -C 12 Alkoxycarbonyl, halogeno C 1 -C 12 Alkoxycarbonyl group, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl, halo C 1 -C 12 Alkoxy radical C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylthio C 1 -C 12 Alkyl, halo C 1 -C 12 Alkylthio group C 1 -C 12 Alkyl radical, C 1 -C 12 Alkoxycarbonyl radical C 1 -C 12 Alkyl, halo C 1 -C 12 Alkoxycarbonyl radical C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylthio carbonyl group C 1 -C 12 Alkyl, halo C 1 -C 12 Alkylthio carbonyl group C 1 -C 12 Alkyl radical, C 1 -C 12 Alkylcarbonyloxy, halo C 1 -C 12 Alkylcarbonyloxy, C 1 -C 12 Alkoxycarbonyloxy, halo C 1 -C 12 Alkoxycarbonyloxy, C 1 -C 12 Alkylsulfonyloxy, halo C 1 -C 12 Alkylsulfonyloxy, C 1 -C 12 Alkoxy radical C 1 -C 12 Alkoxy or halo C 1 -C 12 Alkoxy radical C 1 -C 12 An alkoxy group;
R 5 、R 6 can be the same or different and are respectively selected from hydrogen and C 1 -C 12 Alkyl or halo C 1 -C 12 An alkyl group.
Among the piperidine amine compounds containing pyrimidine of the present invention, preferable compounds include: in the general formula I:
in the compound of the general formula I
R 1 Selected from halogen, cyano, nitro, carboxyl, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl radical, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy radical, C 1 -C 6 Alkylthio radical, C 1 -C 6 Alkylsulfinyl radical, C 1 -C 6 Alkylsulfonyl, halo C 1 -C 6 Alkylthio radical, C 2 -C 6 Alkenyl, halo C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, halo C 2 -C 6 Alkynyl, C 3 -C 6 Alkenyloxy, halogeno C 3 -C 6 Alkenyloxy radical, C 3 -C 6 Alkynyloxy, halo C 3 -C 6 Alkynyloxy, C 1 -C 6 Alkylamino radical, di (C) 1 -C 6 Alkyl) amino, C 1 -C 6 Alkylaminocarbonyl, halogeno C 1 -C 6 Alkylaminocarbonyl radical, C 1 -C 6 Alkoxycarbonyl, halo C 1 -C 6 Alkoxycarbonyl group, C 1 -C 6 Alkoxy radical C 1 -C 6 Alkyl or C 1 -C 6 Alkylthio group C 1 -C 6 An alkyl group;
R 2 selected from halogen, cyano, nitro, amino, carboxyl, formyl, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy or acetal groups;
w is selected from hydrogen, halogen, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 3 -C 6 Cycloalkyl radical, C 1 -C 6 Alkoxy radical, C 1 -C 6 Alkylthio or C 1 -C 6 An alkylsulfonyl group;
R 3 selected from hydrogen, hydroxy, formyl, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy radical, C 3 -C 6 Cycloalkyl radical, C 1 -C 6 Alkylthio radical, C 2 -C 6 Alkenylthio radical, C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, halo C 2 -C 6 Alkenyl, halo C 2 -C 6 Alkynyl, C 1 -C 6 Alkoxy radical C 1 -C 6 Alkyl, halo C 1 -C 6 Alkoxy radical C 1 -C 6 Alkyl radical, C 1 -C 6 Alkylthio group C 1 -C 6 Alkyl, halo C 1 -C 6 Alkylthio group C 1 -C 6 Alkyl radical, C 1 -C 6 Alkylsulfinyl, halogeno C 1 -C 6 Alkylsulfinyl radical, C 1 -C 6 Alkylsulfonyl, halo C 1 -C 6 Alkylsulfonyl radical, C 1 -C 6 Alkylaminosulfonyl, di (C) 1 -C 6 Alkyl) aminosulfonyl, C 1 -C 6 Alkylsulfonylaminocarbonyl group, C 1 -C 6 Alkylcarbonylaminosulfonyl radical, C 3 -C 6 Cycloalkyloxycarbonyl radical, C 1 -C 6 Alkylcarbonyl, halo C 1 -C 6 Alkylcarbonyl group, C 1 -C 6 Alkoxycarbonyl, halo C 1 -C 6 Alkoxycarbonyl group, C 1 -C 6 Alkyl carbonyl radical C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxycarbonyl radical C 1 -C 6 Alkyl radical, C 1 -C 6 Alkylaminocarbonyl, di (C) 1 -C 6 Alkyl) aminocarbonyl, C 2 -C 6 Alkenyloxycarbonyl radical, C 2 -C 6 Alkynyloxycarbonyl group, C 1 -C 6 Alkoxy radical C 1 -C 6 Alkoxycarbonyl group, C 1 -C 6 Alkylamino thio, di (C) 1 -C 6 Alkyl) aminosulfanyl, (hetero) arylcarbonyl C which is unsubstituted or further substituted by 1 to 5 1 -C 6 Alkyl, (hetero) arylcarbonyl, (hetero) aryloxycarbonyl, (hetero) aryl C 1 -C 6 Alkyloxycarbonyl, (hetero) aryl C 1 -C 6 Alkyl groups: halogen, nitro, cyano, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy or halo C 1 -C 6 An alkoxy group;
q is selected from Q 1 、Q 2 、Q 3 、Q 4 、Q 5 、Q 6 Naphthyl, quinolyl, isoquinolyl, quinazolinyl, o-diazonaphthyl, phthalazinyl, quinoxalinyl, 1,8-naphthyridinyl, 1,7-naphthyridinyl, 1,6-naphthyridinyl, 1,5-naphthyridinyl, pyrido [2,3-d]Pyrimidinyl, pyrido [3,2-d]Pyrimidinyl, pyrido [2,3-b]Pyrazinyl, pyrido [2,3-c]Pyridazinyl, pyrido [2,3-d]Pyridazinyl, benzo [ d ]]Imidazolyl, indazolyl, benzo [ d ]]Thiazolyl, benzo [ d ]]Isothiazolyl, benzo [ d ]]Oxazolyl, benzo [ d ]]Isoxazolyl, benzo [ b ]]Thienyl, benzofuranonyl, or indolyl;
wherein Q is 1 Selected from the group consisting of 1-5R 4 Substituted phenyl, with R 4 At least 1 of them is an electron-withdrawing group; and the benzene ring is not substituted by monofluorine; and does not comprise the following compounds: 6-ethyl-5-fluoro-N- (1- (2-fluoro-5-methylphenyl) -piperidin-4-yl) pyrimidin-4-amine;
Q 2 selected from the group consisting of 0-4R 4 A substituted pyridyl group; and does not comprise the following compounds:
5-chloro-6-ethyl-N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine; 5-methoxy-6- (methoxymethyl) -N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine;
Q 3 selected from the group consisting of 0-3R 4 A substituted pyrimidinyl group; and Q 3 Is not unsubstituted 2-pyrimidinyl; and does not comprise the following compounds: n- (1- (2,6-dimethylpyrimidin-4-yl) piperidin-4-yl) -6-ethyl-5-fluoropyrimidin-4-amine;
Q 4 selected from the group consisting of 0-3R 4 A substituted 3-pyridazinyl group; and does not include the following compounds:
2-cyclopropyl-5-methoxy-6-methyl-N- (1- (pyridazin-3-yl) piperidin-4-yl) pyrimidin-4-amine;
Q 5 selected from the group consisting of 0-3R 4 A substituted 2-pyrazinyl group;
Q 6 selected from the group consisting of 0-2R 4 Substituted s-triazinyl or s-triazinyl;
R 4 selected from halogen, carboxyl, aldehyde group, amino, cyano, nitro, C 1 -C 6 Alkyl, halo C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxy, halo C 1 -C 6 Alkoxy radical, C 3 -C 6 Cycloalkyl, C 1 -C 6 Alkylamino, halogeno C 1 -C 6 Alkylamino radical, di (C) 1 -C 6 Alkyl) amino, halo-di (C) 1 -C 6 Alkyl) amino, C (= O) NR 5 R 6 、C 1 -C 6 Alkylcarbonylamino, C 1 -C 6 Alkylthio, halogeno C 1 -C 6 Alkylthio radical, C 2 -C 6 Alkenyl radical, C 2 -C 6 Alkynyl, C 2 -C 6 Alkenyloxy, halogeno C 2 -C 6 Alkenyloxy radical, C 2 -C 6 Alkynyloxy, halo C 2 -C 6 Alkynyloxy, C 1 -C 6 Alkylsulfonyl, halo C 1 -C 6 Alkylsulfonyl radical, C 1 -C 6 Alkylcarbonyl, halo C 1 -C 6 Alkylcarbonyl group, C 1 -C 6 Alkoxycarbonyl, halo C 1 -C 6 Alkoxycarbonyl group, C 1 -C 6 Alkoxy radical C 1 -C 6 Alkyl, halo C 1 -C 6 Alkoxy radical C 1 -C 6 Alkyl radical, C 1 -C 6 Alkylthio group C 1 -C 6 Alkyl, halo C 1 -C 6 Alkylthio group C 1 -C 6 Alkyl radical, C 1 -C 6 Alkoxycarbonyl radical C 1 -C 6 Alkyl, halo C 1 -C 6 Alkoxycarbonyl radical C 1 -C 6 Alkyl radical, C 1 -C 6 Alkylthio carbonyl group C 1 -C 6 Alkyl, halo C 1 -C 6 Alkylthio carbonyl group C 1 -C 6 Alkyl radical, C 1 -C 6 Alkylcarbonyloxy, halo C 1 -C 6 Alkylcarbonyloxy, C 1 -C 6 Alkoxycarbonyloxy, halo C 1 -C 6 Alkoxycarbonyloxy, C 1 -C 6 Alkylsulfonyloxy, halo C 1 -C 6 Alkylsulfonyloxy, C 1 -C 6 Alkoxy radical C 1 -C 6 Alkoxy or halo C 1 -C 6 Alkoxy radical C 1 -C 6 An alkoxy group;
R 5 、R 6 can be the same or different and are respectively selected from hydrogen and C 1 -C 12 Alkyl or halo C 1 -C 12 An alkyl group.
Among the pyrimidine-containing piperidinamines of the present invention, further preferred compounds include: the structural formula of the general formula I is shown as I-1;
Figure BDA0002747185910000041
in the formula, R 1 Selected from halogen, cyano, nitro, carboxyl, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 3 -C 4 Cycloalkyl, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy radical, C 1 -C 4 Alkylthio radical, C 1 -C 4 Alkylsulfinyl radical, C 1 -C 4 Alkylsulfonyl, halo C 1 -C 4 Alkylthio radical, C 2 -C 4 Alkenyl, halo C 2 -C 4 Alkenyl radical, C 2 -C 4 Alkynyl, halo C 2 -C 4 Alkynyl, C 3 -C 4 Alkenyloxy, halogeno C 3 -C 4 Alkenyloxy radical, C 3 -C 4 Alkynyloxy, halo C 3 -C 4 Alkynyloxy, C 1 -C 4 Alkylamino radical, di (C) 1 -C 4 Alkyl) amino, C 1 -C 4 Alkylaminocarbonyl, halogeno C 1 -C 4 Alkylaminocarbonyl radical, C 1 -C 4 Alkoxycarbonyl, halo C 1 -C 4 Alkoxycarbonyl group, C 1 -C 4 Alkoxy radical C 1 -C 4 Alkyl or C 1 -C 4 Alkylthio C 1 -C 4 An alkyl group;
R 2 selected from halogen, cyano, nitro, amino, carboxyl, formyl, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy or acetal groups;
w is selected from hydrogen, halogen, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 3 -C 4 Cycloalkyl radical, C 1 -C 4 Alkoxy radical, C 1 -C 4 Alkylthio or C 1 -C 4 An alkylsulfonyl group;
q is selected from Q 1 、Q 2 、Q 3 、Q 4 、Q 5 Or Q 6 ；
Wherein Q is 1 Selected from the group consisting of 1-5R 4 Substituted phenyl, with R 4 At least 1 of them is an electron-withdrawing group; and the benzene ring is not substituted by monofluorine; and does not comprise the following compounds: 6-ethyl-5-fluoro-N- (1- (2-fluoro-5-methylphenyl) -piperidin-4-yl) pyrimidin-4-amine;
Q 2 selected from the group consisting of 0-4R 4 A substituted pyridyl group; and does not comprise the following compounds:
5-chloro-6-ethyl-N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine; 5-methoxy-6- (methoxymethyl) -N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine;
Q 3 selected from the group consisting of 1-3R 4 Substituted 2-pyrimidinyl or substituted by 0-3R 4 Substituted 4-pyrimidinyl; and does not comprise the following compounds: n- (1- (2,6-dimethylpyrimidin-4-yl) piperidin-4-yl) -6-ethyl-5-fluoropyrimidin-4-amine;
Q 4 selected from the group consisting of 0-3R 4 A substituted 3-pyridazinyl group; and does not include the following compounds:
2-cyclopropyl-5-methoxy-6-methyl-N- (1- (pyridazin-3-yl) piperidin-4-yl) pyrimidin-4-amine;
Q 5 selected from the group consisting of 0-3R 4 A substituted 2-pyrazinyl group;
Q 6 selected from the group consisting of 0-2R 4 Substituted s-triazinyl or s-triazinyl;
R 4 selected from halogen, carboxyl, aldehyde group, amino, cyano, nitro, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy radical, C 3 -C 4 Cycloalkyl, C 1 -C 4 Alkylamino, halogeno C 1 -C 4 Alkylamino radical, di (C) 1 -C 4 Alkyl) amino, halo-di (C) 1 -C 4 Alkyl) amino, C (= O) NR 5 R 6 、C 1 -C 4 Alkylcarbonylamino, C 1 -C 4 Alkylthio, halo C 1 -C 4 Alkylthio radical, C 2 -C 4 Alkenyl radical, C 2 -C 4 Alkynyl, alkynyl,C 2 -C 4 Alkenyloxy, halogeno C 2 -C 4 Alkenyloxy radical, C 2 -C 4 Alkynyloxy, halo C 2 -C 4 Alkynyloxy, C 1 -C 4 Alkylsulfonyl, halo C 1 -C 4 Alkylsulfonyl radical, C 1 -C 4 Alkylcarbonyl, halo C 1 -C 4 Alkylcarbonyl group, C 1 -C 4 Alkoxycarbonyl, halo C 1 -C 4 Alkoxycarbonyl group, C 1 -C 4 Alkoxy radical C 1 -C 4 Alkyl, halo C 1 -C 4 Alkoxy radical C 1 -C 4 Alkyl radical, C 1 -C 4 Alkylthio group C 1 -C 4 Alkyl, halo C 1 -C 4 Alkylthio group C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxycarbonyl radical C 1 -C 4 Alkyl, halo C 1 -C 4 Alkoxycarbonyl radical C 1 -C 4 Alkyl radical, C 1 -C 4 Alkylthio carbonyl group C 1 -C 4 Alkyl, halo C 1 -C 4 Alkylthio carbonyl group C 1 -C 4 Alkyl radical, C 1 -C 4 Alkylcarbonyloxy, halo C 1 -C 4 Alkylcarbonyloxy, C 1 -C 4 Alkoxycarbonyloxy, halo C 1 -C 4 Alkoxycarbonyloxy, C 1 -C 4 Alkylsulfonyloxy, halo C 1 -C 4 Alkylsulfonyloxy, C 1 -C 4 Alkoxy radical C 1 -C 4 Alkoxy or halo C 1 -C 4 Alkoxy radical C 1 -C 4 An alkoxy group;
R 5 、R 6 can be the same or different and are respectively selected from hydrogen and C 1 -C 12 Alkyl or halo C 1 -C 12 An alkyl group.
Among the pyrimidine-containing piperidinamines of the present invention, still further preferred compounds include: the structure of the compound shown in the general formula I-1 is as follows: I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I, I-1J;
Figure BDA0002747185910000051
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Figure BDA0002747185910000061
in the formula:
R 1 selected from halogen, cyano, nitro, carboxyl, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 3 -C 4 Cycloalkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy radical, C 1 -C 4 Alkylthio, halo C 1 -C 4 Alkylthio radical, C 1 -C 4 Alkylsulfinyl radical, C 1 -C 4 Alkylsulfonyl radical, C 2 -C 4 Alkenyl, halo C 2 -C 4 Alkenyl radical, C 2 -C 4 Alkynyl, halo C 2 -C 4 Alkynyl, C 3 -C 4 Alkenyloxy, halogeno C 3 -C 4 Alkenyloxy radical, C 3 -C 4 Alkynyloxy, halo C 3 -C 4 Alkynyloxy, C 1 -C 4 Alkylamino radical, di (C) 1 -C 4 Alkyl) amino, C 1 -C 4 Alkylaminocarbonyl, halogeno C 1 -C 4 Alkylaminocarbonyl radical, C 1 -C 4 Alkoxycarbonyl, halo C 1 -C 4 Alkoxycarbonyl group, C 1 -C 4 Alkoxy radical C 1 -C 4 Alkyl or C 1 -C 4 Alkylthio group C 1 -C 4 An alkyl group;
R 2 selected from halogen, cyano, nitro, amino, carboxyl, formyl, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy or halo C 1 -C 4 Alkoxy or acetal groups;
w is selected from hydrogen, halogen, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 3 -C 4 Cycloalkyl radical, C 1 -C 4 Alkoxy radical, C 1 -C 4 Alkylthio or C 1 -C 4 An alkylsulfonyl group;
n is selected from 0, 1,2, 3 and 4;
R 4 selected from halogen, carboxyl, aldehyde group, amino, cyano, nitro, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy radical, C 3 -C 4 Cycloalkyl radical, C 1 -C 4 Alkylamino, halogeno C 1 -C 4 Alkylamino radical, di (C) 1 -C 4 Alkyl) amino, halo-di (C) 1 -C 4 Alkyl) amino, C (= O) NR 5 R 6 、C 1 -C 4 Alkylcarbonylamino, C 1 -C 4 Alkylthio, halo C 1 -C 4 Alkylthio radical, C 2 -C 4 Alkenyl radical, C 2 -C 4 Alkynyl, C 2 -C 4 Alkenyloxy, halogeno C 2 -C 4 Alkenyloxy radical, C 2 -C 4 Alkynyloxy, halo C 2 -C 4 Alkynyloxy, C 1 -C 4 Alkylsulfonyl, halo C 1 -C 4 Alkylsulfonyl radical, C 1 -C 4 Alkylcarbonyl, halo C 1 -C 4 Alkylcarbonyl group, C 1 -C 4 Alkoxycarbonyl, halogeno C 1 -C 4 Alkoxycarbonyl group, C 1 -C 4 Alkoxy radical C 1 -C 4 Alkyl, halo C 1 -C 4 Alkoxy radical C 1 -C 4 Alkyl radical, C 1 -C 4 Alkylthio group C 1 -C 4 Alkyl, halo C 1 -C 4 Alkylthio group C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxycarbonyl radical C 1 -C 4 Alkyl, halo C 1 -C 4 Alkoxycarbonyl radical C 1 -C 4 Alkyl radical, C 1 -C 4 Alkylthio carbonyl group C 1 -C 4 Alkyl, halo C 1 -C 4 Alkylthio carbonyl group C 1 -C 4 Alkyl radical, C 1 -C 4 Alkylcarbonyloxy, halo C 1 -C 4 Alkylcarbonyloxy, C 1 -C 4 Alkoxycarbonyloxy, halo C 1 -C 4 Alkoxycarbonyloxy, C 1 -C 4 Alkylsulfonyloxy, halo C 1 -C 4 Alkylsulfonyloxy, C 1 -C 4 Alkoxy radical C 1 -C 4 Alkoxy or halo C 1 -C 4 Alkoxy radical C 1 -C 4 An alkoxy group;
wherein, in the general formula I-1D, n =1-4, and R 4 At least 1 of them is an electron-withdrawing group; and the benzene ring is not substituted by monofluorine; and does not comprise the following compounds: 6-ethyl-5-fluoro-N- (1- (2-fluoro-5-methylphenyl) -piperidin-4-yl) pyrimidin-4-amine;
in the general formulas I-1A, I-1B and I-1C, n =0-4; and does not comprise the following compounds:
5-chloro-6-ethyl-N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine; 5-methoxy-6- (methoxymethyl) -N- (1- (5- (trifluoromethyl) pyridin-2-yl) piperidin-4-yl) pyrimidin-4-amine;
general formula I-1E, n =0-3, general formula I-1F, n =1-3; and does not comprise the following compounds: n- (1- (2,6-dimethylpyrimidin-4-yl) piperidin-4-yl) -6-ethyl-5-fluoropyrimidin-4-amine;
in formulae 1-1G, n =0-3; and does not include the following compounds:
2-cyclopropyl-5-methoxy-6-methyl-N- (1- (pyridazin-3-yl) piperidin-4-yl) pyrimidin-4-amine.
In the general formula I-1H, n =0-3;
in the general formulas I-1I and I-1J, n =0-2;
R 5 、R 6 can be the same or different and are respectively selected from hydrogen and C 1 -C 4 Alkyl or halo C 1 -C 4 An alkyl group.
Among the pyrimidine-containing piperidinamines of the present invention, further preferred compounds include: compounds shown in general formulas I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I and I-1J;
R 1 selected from halogen, cyano, nitro, carboxyl, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 An alkoxy group;
R 2 selected from halogen, cyano, nitro, amino, carboxyl, formyl, C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy or halo C 1 -C 4 An alkoxy or acetal group;
w is selected from hydrogen, halogen, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 3 -C 4 Cycloalkyl radical, C 1 -C 4 Alkoxy radical, C 1 -C 4 Alkylthio or C 1 -C 4 An alkylsulfonyl group;
n is selected from 0, 1,2, 3 and 4;
R 4 selected from halogen, carboxyl, aldehyde group, amino, cyano, nitro, C 1 -C 4 Alkyl, halo C 1 -C 4 Alkyl radical, C 1 -C 4 Alkoxy, halo C 1 -C 4 Alkoxy, C (= O) NR 5 R 6 、C 1 -C 4 Alkylcarbonylamino, C 1 -C 4 An alkoxycarbonyl group;
R 5 、R 6 can be the same or different and are respectively selected from hydrogen and C 1 -C 4 Alkyl or halo C 1 -C 4 An alkyl group.
Among the pyrimidine-containing piperidinamines of the present invention, further preferred compounds include: in the compounds shown in the general formulas I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I and I-1J:
R 1 selected from fluoro, chloro, bromo, iodo, cyano, nitro, carboxy, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, monofluoromethyl, monochloromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, methoxymethyl, ethoxymethyl or trifluoroethoxymethyl;
R 2 selected from fluorine, chlorine, bromine, iodine, cyano, nitro, amino, carboxyl, formyl, methyl, ethyl, methoxy, ethoxy or trifluoroethoxy,An acetal group;
w is selected from hydrogen, fluoro, chloro, bromo, iodo, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, monofluoromethyl, monochloromethyl, difluoromethyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, methylthio, ethylthio, methylsulfonyl or ethylsulfonyl;
n is selected from 0, 1,2 and 3;
R 4 selected from the group consisting of fluoro, chloro, bromo, iodo, carboxy, aldehyde, cyano, amino, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, difluoromethyl, trifluoromethyl, trichloromethyl, chloromethyl, difluorochloromethyl, dichlorofluoromethyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, tert-butoxy, trifluoromethoxy, trifluoroethoxy, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, methylcarbonylamino, methylaminocarbonyl, ethylaminocarbonyl, or dimethylaminocarbonyl.
Still more preferred compounds of the piperidine amines containing pyrimidine according to the invention include: in the compounds shown in general formulas I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I and I-1J:
R 1 selected from fluoro, chloro, bromo, iodo, methyl, ethyl or difluoromethyl;
R 2 selected from fluoro, chloro, bromo, iodo, nitro, amino, formyl, methyl, ethyl, methoxy, ethoxy or acetal groups;
w is selected from hydrogen, fluorine, chlorine, bromine, iodine or methyl;
n is selected from 0, 1,2 and 3;
R 4 selected from fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, chloromethyl, difluoromethyl, trifluoromethyl, trichloromethyl, methoxy, methoxycarbonyl or trifluoromethoxy.
Still more preferred compounds of the piperidine amines containing pyrimidine according to the invention include: in the compounds shown in general formulas I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I and I-1J:
R 1 selected from fluoro, chloro, bromo, iodo, methyl, ethyl or difluoromethyl;
R 2 selected from fluoro, chloro, bromo, iodo, nitro, amino, formyl, methyl, methoxy or acetal groups;
w is selected from hydrogen;
n is selected from 0, 1,2 and 3;
R 4 selected from fluorine, chlorine, bromine, iodine, carboxyl, aldehyde group, cyano, nitro, methyl, ethyl, difluoromethyl, trifluoromethyl, trichloromethyl, methoxy, methoxycarbonyl or trifluoromethoxy.
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. Electron withdrawing groups include: (nitro: -NO) 2 . Cyano group: -CN. Tertiary amine cation-NR 3 . Sulfonic acid group-SO 3 H. Trihalomethyl group: -CX 3 X = F, cl, br, I. Formyl group: -CHO. Acyl group: -CO-alkoxy. Carboxyl group: -COOH. Halogen atom: F. cl, br, I) alkyl: straight-chain or branched alkyl groups, such as methyl, ethyl, propyl, isopropyl, n-butyl or tert-butyl. Cycloalkyl: substituted or unsubstituted cyclic alkyl groups, such as cyclopropyl, cyclopentyl or cyclohexyl. Substituents such as methyl, halogen, and the like. A haloalkyl group: 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. 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. Haloalkylsulfonyl group: straight-chain or branched alkylsulfonyl wherein the hydrogen atoms of the alkyl group may be partially or wholly substituted by halogen atoms. Alkylaminosulfenyl: such as CH 3 NHS-、C 2 H 5 NHS-. A dialkylaminosulfenyl group: such as (CH) 3 ) 2 NS-、 (C 2 H 5 ) 2 NS-. Alkylamino sulfonyl group: alkyl-NH-SO 2 -. Dialkylaminosulfonyl: (alkyl group) 2 -N-SO 2 -. Alkylsulfonylaminocarbonyl group: alkyl-SO 2 -NH-CO-. Alkylcarbonylaminosulfonyl: alkyl-CO-NH-SO 2 -. Alkylcarbonylalkyl group: alkyl-CO-alkyl-. Alkylsulfonyloxy group: alkyl-S (O) 2 -O-. Haloalkylsulfonyloxy: the hydrogen atoms of the alkyl group of the alkylsulfonyloxy group may be partially or wholly substituted by halogen atoms, e.g. CF 3 -SO 2 -O. Cycloalkyloxycarbonyl group: such as cyclopropyloxycarbonyl, cyclohexyloxycarbonyl, 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. Halogenated alkoxycarbonyl group: the hydrogen atoms of the alkyl group of the alkoxycarbonyl group may be partially or wholly replaced by halogen atoms, e.g. ClCH 2 CH 2 OCO-、CF 3 CH 2 OCO-, etc. An alkoxyalkyl group: alkyl-O-alkyl-, e.g. CH 3 OCH 2 -. Haloalkoxyalkyl groups: the hydrogen atoms of the alkyl groups of alkoxyalkyl groups may be partially or fully substituted by halogen atoms, e.g. ClCH 2 CH 2 OCH 2 -、 CF 3 CH 2 OCH 2 -and the like. Alkoxycarbonylalkyl groups: alkoxycarbonyl-alkyl-, e.g. CH 3 OCOCH 2 -. Haloalkoxycarbonylalkyl: the hydrogen atoms of the alkyl group of the alkoxycarbonylalkyl group may be partially or fully substituted by halogen atoms, e.g. CF 3 CH 2 OCOCH 2 -. Alkylcarbonyloxy group: such as CH 3 COO-, etc. Haloalkylcarbonyloxy: the hydrogen atoms of the alkylcarbonyloxy group may be partially or fully substituted by halogen atoms, e.g. CF 3 COO-, etc. Alkoxycarbonyloxy: alkoxycarbonyl-oxy-, e.g. CH 3 OCOO-. Haloalkoxycarbonyl group: the hydrogen atoms of the alkyl group of the alkoxycarbonyloxy group may be partially or wholly substituted by halogen atoms, e.g. CF 3 OCOO-. Alkylthio-carbonylalkyl: alkylthiocarbonyl-alkyl-, e.g. CH 3 SCOCH 2 -. Haloalkylthiocarbonylalkyl: the hydrogen atoms of the alkyl group of the alkylthiocarbonylalkyl group may be partially or wholly replaced by halogen atoms, e.g. CF 3 CH 2 SCOCH 2 -. Alkoxy groups: such as CH 3 OCH 2 O-, etc. Haloalkoxyalkyl: the hydrogen atoms of the alkoxy groups being partially or wholly replaced by halogen atoms, e.g. CF 3 OCH 2 O-is added. Alkoxy alkoxycarbonyl group: such as CH 3 OCH 2 CH 2 OCO-, etc. Alkylthio group: straight or branched chain alkyl groups attached to the structure via a sulfur atom. Halogenated alkylthio groups: 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. Alkylthioalkyl: alkyl-S-alkyl-, e.g. CH 3 SCH 2 -. Haloalkylthioalkyl: the hydrogen atoms of the alkyl group of an alkylthioalkyl group may be partially or fully substituted by halogen atoms, e.g. ClCH 2 CH 2 SCH 2 -、CF 3 CH 2 SCH 2 -and the like. Alkylamino group: straight or branched chain alkyl groups attached 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 ) 2 N-，(CH 3 CH 2 ) 2 N-is provided. Halogenated dialkylamino group: the hydrogen atoms of the alkyl groups being partially or wholly replaced by halogen atoms, e.g. (CF) 3 ) 2 N-，(CF 3 CH 2 ) 2 N-is provided. 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. Alkenyloxy: linear or branched alkenes linked to the structure via oxygen atoms. Haloalkenyloxy: linear or branched alkenyloxyThe hydrogen atoms on these alkenyloxy groups may be partially or completely substituted with halogen atoms. Alkenylthio group: linear or branched alkenes linked to the structure via a sulfur atom bond. Such as CH 2 ＝CHCH 2 S-. Alkenyloxycarbonyl radical: such as CH 2 ＝CHCH 2 OCO-, etc. 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. Alkynyloxy: straight or branched alkynes, attached 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. Alkynyloxycarbonyl group: such as CH ≡ CCH 2 OCO-, etc. 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. CH 3 CO-，CH 3 CH 2 CO-. 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. CF 3 CO-. Alkoxycarbonyl group: the alkoxy group is attached to the structure via a carbonyl group. Such as CH 3 OCO-，CH 3 CH 2 OCO-. Aminocarbonyl group: such as NH 2 CO-. Alkyl amino carbonyl: alkyl-NH-CO-, e.g. CH 3 NHCO-， CH 3 CH 2 NHCO-. Dialkylaminocarbonyl group: such as (CH) 3 ) 2 NCO-，(CH 3 CH 2 ) 2 NCO-. The aryl moiety in (hetero) aryl, (hetero) arylalkyl, (hetero) arylcarbonyl, (hetero) arylmethylcarbonyl, (hetero) arylcarbonylalkyl, (hetero) aryloxycarbonyl, (hetero) arylalkyloxycarbonyl, and the like includes phenyl or naphthyl. Heteroaryl is a five or six membered ring containing 1 or more N heteroatoms. Such as pyridyl, pyrimidinyl, pyrazinonyl, pyridazinyl, triazinyl and the like. (hetero) aryl group: such as phenyl, and the like.
Table 1, table 2, table 3 and Table 4 show the R in the general formula I 1 、R 2 、R 3 And a part of W are specifically substituents, but they are not limited to these substituents.
Figure BDA0002747185910000091
TABLE 1R 1 Substituent group
Figure BDA0002747185910000092
Figure BDA0002747185910000101
TABLE 2R 2 Substituent group
Figure BDA0002747185910000102
TABLE 3R 3 Substituent group
Figure BDA0002747185910000103
/>
Figure BDA0002747185910000111
TABLE 4W substituents
Figure BDA0002747185910000112
Some of the compounds of the present invention can be illustrated by specific compounds listed in tables 5 to 114, but are not intended to limit the present invention. In the general formula compounds I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I, I-1J referred to in the table, W = R 3 ＝H。
In the general formula I-1A, some of the compounds of the present invention are represented by the compounds shown in tables 5 to 15;
Figure BDA0002747185910000121
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 5, and represent the compound numbers of 5-1-5-198 in sequence.
TABLE 5
Figure BDA0002747185910000122
/>
Figure BDA0002747185910000131
Table 6: in the general formula I-1A, when R is 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 of Table 5, the compound numbers are in turn 6-1-6-198.
Table 7: in the general formula I-1A, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 of Table 5, the compound numbers are in turn 7-1-7-198.
Table 8: in the general formula I-1A, when R is 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 of Table 5, the compound numbers are in turn 8-1-8-198.
Table 9: in the general formula I-1A, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 of Table 5, representing the compound numbers 9-1-9-198 in turn.
Table 10: in the general formula I-1A, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to the table 5 in sequence5-1-5-198 of 5, representing compound numbers 10-1-10-198 in sequence.
Table 11: in the general formula I-1A, when R 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 in Table 5, the compound numbers are in turn 11-1-11-198.
Table 12: in the general formula I-1A, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 of Table 5, the compound numbers are in turn 12-1-12-198.
Table 13: in the general formula I-1A, when R 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 of Table 5, the compound numbers are in turn 13-1-13-198.
TABLE 13-1: in the general formula I-1A, when R is 1 ＝CH 3 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 in Table 5, representing the compound numbers 13-1-13-1-198 in turn.
Table 14: in the general formula I-1A, when R is 1 ＝C 2 H 5 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 of Table 5, the compound numbers are in turn 14-1-14-198.
TABLE 14-1: in the general formula I-1A, when R 1 ＝C 2 H 5 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 in Table 5, the compound numbers are 14-1-14-1-198 in turn.
Table 15: in the general formula I-1A, when R is 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 5 in turn to 5-1-5-198 in Table 5, the compound numbers are 15-1-15-198 in turn.
Table 15-1: in the general formula I-1A, when R is 1 ＝CHF 2 、R 2 (= F), substituent (R) 4 ) n In accordance with Table 5, the data of Table 5 are sequentially mapped5-1-5-198, which represents a compound number of 15-1-15-1-198 in sequence.
In the general formula I-1B, some of the compounds of the present invention are represented by the compounds shown in tables 16 to 26;
Figure BDA0002747185910000141
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 16, and represent the compound numbers of 16-1-16-198 in sequence.
TABLE 16
Figure BDA0002747185910000142
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Figure BDA0002747185910000151
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Figure BDA0002747185910000161
Table 17: in the general formula I-1B, when R is 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding to Table 16 in turn to 16-1 to 16-198 in Table 16, the numbers of the representative compounds are in turn 17-1 to 17-198.
Table 18: in the general formula I-1B, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 of Table 16, the compound numbers are in turn 18-1-18-198.
Table 19: in the general formula I-1B, when R is 1 ＝Cl、R 2 = CHO, substituent (R) 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 of Table 16, the compound numbers are in turn 19-1-19-198.
Table 20: in the general formula I-1B, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding to Table 16 in sequence from 16-1 to 16-198 of Table 16, representing compound numbers from 20-1 to 20-198 in sequence.
Table 21: in the general formula I-1B, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 in Table 16, the compound numbers are in turn 21-1-21-198.
Table 22: in the general formula I-1B, when R is 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 in Table 16, the compound numbers are in turn 22-1-22-198.
Table 23: in the general formula I-1B, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to Table 16 in this order to 16-1-16-198 in Table 16, the numbers of the representative compounds are 23-1-23-198 in this order.
Table 24: in the general formula I-1B, when R is 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 of Table 16, the compound numbers are in turn 24-1-24-198.
Table 24-1: in the general formula I-1B, when R is 1 ＝CH 3 、R 2 (= F), substituent (R) 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 in Table 16, the compound numbers are in turn 24-1-24-1-198.
Table 25: in the general formula I-1B, when R is 1 ＝C 2 H 5 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 16 in sequence from 16-1 to 16-198 of Table 16, representing compound numbers from 25-1 to 25-198 in sequence.
TABLE 25-1: in the general formula I-1B, when R is 1 ＝C 2 H 5 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 in Table 16, representing the compound numbers 25-1-25-1-198 in turn.
Table 26: in the general formula I-1B, when R is 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 in Table 16, the compound numbers are in turn 26-1-26-198.
TABLE 26-1: in the general formula I-1B, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 16 in turn to 16-1-16-198 in Table 16, representing the compound numbers 26-1-26-1-198 in turn.
In the general formula I-1C, some of the compounds of the present invention are represented by the compounds shown in tables 27 to 37;
Figure BDA0002747185910000162
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when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 27, and represent the compound numbers of 27-1-27-135 in sequence.
Watch 27
Figure BDA0002747185910000163
Figure BDA0002747185910000171
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Table 28: in the general formula I-1C, when R 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding to Table 27 in this order to 27-1 to 27-135 in Table 27, the numbers of the representative compounds are 28-1 to 28-135 in this order.
Table 29: in the general formula I-1C, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n Corresponding to Table 27 in this order, 27-1 to 27-135 in Table 27, represent the numbers of the compounds in this order, 29-1 to 29-135.
Table 30: in the general formula I-1C, when R is 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n Corresponding in sequence to 27-1-27-135 of Table 27 in agreement with Table 27, represents the compoundThe numbers of the materials are 30-1 to 30-135 in sequence.
Table 31: in the general formula I-1C, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding to Table 27 in this order, 27-1 to 27-135 in Table 27, represent the numbers of the compounds 31-1 to 31-135 in this order.
Table 32: in the general formula I-1C, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to Table 27 in this order, 27-1 to 27-135 in Table 27, represent the numbers of the compounds in this order, 32-1 to 32-135.
Table 33: in the general formula I-1C, when R is 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding to Table 27 in this order to 27-1 to 27-135 in Table 27, the numbers of the representative compounds are 33-1 to 33-135 in this order.
Table 34: in the general formula I-1C, when R 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to Table 27 in this order to 27-1 to 27-135 of Table 27, and representing the numbers of the compounds in this order of 34-1 to 34-135.
Table 35: in the general formula I-1C, when R 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 27 in this order to 27-1 to 27-135 in Table 27, the numbers of the representative compounds are 35-1 to 35-135 in this order.
TABLE 35-1: in the general formula I-1C, when R is 1 ＝CH 3 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 27 in this order, 27-1 to 27-135 in Table 27, the numbers of the representative compounds are 35-1-1 to 35-1 to 135 in this order.
Table 36: in the general formula I-1C, when R is 1 ＝C 2 H 5 、R 2 (= Cl), substituent (R) 4 ) n Corresponding to Table 27 in this order, 27-1 to 27-135 in Table 27, represent the numbers of the compounds 36-1 to 36-135 in this order.
TABLE 36-1: in the general formula I-1C, when R is 1 ＝C 2 H 5 、R 2 When = F, substituent (R) 4 ) n In agreement with Table 27, the generations of 27-1-27-135 of Table 27 are corresponded in orderThe compound numbers in the table are 36-1-36-1-135 in sequence.
Table 37: in the general formula I-1C, when R 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 27 in this order, 27-1 to 27-135 in Table 27, represent the numbers of the compounds 37-1 to 37-135 in this order.
TABLE 37-1: in the general formula I-1C, when R 1 ＝CHF 2 、R 2 (= F), substituent (R) 4 ) n Corresponding to Table 27 in this order, 27-1 to 27-135 in Table 27, represent the numbers of the compounds 37-1-1 to 37-1 to 135 in this order.
In the general formula I-1D, some of the compounds of the present invention are represented by the compounds shown in tables 38 to 48;
Figure BDA0002747185910000181
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 38, and represent the compound numbers 38-1-38-258 in sequence.
Watch 38
Figure BDA0002747185910000182
Figure BDA0002747185910000191
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Figure BDA0002747185910000201
Table 39: in the general formula I-1D, when R 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding in sequence to Table 38 in Table 38, 38-1-38-258 in Table 38, represents the compound numbers in sequence 39-1-39-258.
Table 40: in the general formula I-1D, when R is 1 ＝Cl、R 2 ＝OCH 3 When the utility model is used, the water is discharged,substituent (R) 4 ) n Corresponding to Table 38 in turn to 38-1-38-258 in Table 38, the compound numbers are in turn 40-1-40-258.
Table 41: in the general formula I-1D, when R 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n Corresponding to Table 38 in the order 38-1-38-258 of Table 38, representing the compound numbers 41-1-41-258 in the order.
Table 42: in the general formula I-1D, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding in sequence to Table 38 in Table 38, 38-1-38-258 in Table 38, represents the compound numbers 42-1-42-258 in sequence.
Table 43: in the general formula I-1D, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to Table 38 in the order 38-1-38-258 of Table 38, representing the compound numbers in the order 43-1-43-258.
Table 44: in the general formula I-1D, when R is 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding in sequence to Table 38 in Table 38, 38-1-38-258, represents compound numbers in sequence of 44-1-44-258.
Table 45: in the general formula I-1D, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to Table 38 in sequence, 38-1-38-258 of Table 38, represents the compound numbers 45-1-45-258 in sequence.
Table 46: in the general formula I-1D, when R is 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n Corresponding in sequence to Table 38 in Table 38, 38-1-38-258, represents compound numbers in sequence 46-1-46-258.
TABLE 46-1: in the general formula I-1D, when R is 1 ＝CH 3 、R 2 (= F), substituent (R) 4 ) n In agreement with Table 38, this corresponds in turn to 38-1-38-258 of Table 38, representing the compound numbers 46-1-46-1-258 in turn.
Table 47: in the general formula I-1D, when R is 1 ＝C 2 H 5 、R 2 When = Cl, substituent (R) 4 ) n In agreement with Table 38, this corresponds in turn to 38-1-38-258 of Table 38, representing the compound numbers 47-1-47-258 in turn.
TABLE 47-1: in the general formula I-1D, when R is 1 ＝C 2 H 5 、R 2 (= F), substituent (R) 4 ) n In agreement with Table 38, this corresponds in turn to 38-1-38-258 of Table 38, representing the compound numbers 47-1-47-1-258 in turn.
Table 48: in the general formula I-1D, when R 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 38 in the order 38-1-38-258 of Table 38, representing the compound numbers in the order 48-1-48-258.
TABLE 48-1: in the general formula I-1D, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 38 in turn to 38-1-38-258 in Table 38, the compound numbers are in turn 48-1-48-1-258.
In the general formula I-1E, some of the compounds of the present invention are represented by the compounds shown in tables 49 to 59;
Figure BDA0002747185910000211
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 49 and represent the compound numbers 49-1-49-72 in sequence.
Watch 49
Figure BDA0002747185910000212
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Figure BDA0002747185910000221
TABLE 50: in the general formula I-1E, when R 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding in sequence to 49-1-49-72 of Table 49 in accordance with Table 49 represents a compoundThe serial numbers of the materials are 50-1 to 50-72.
Table 51: in the general formula I-1E, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n In agreement with Table 49, this corresponds in turn to 49-1-49-72 of Table 49 and represents the compound numbers 51-1-51-72 in turn.
Table 52: in the general formula I-1E, when R is 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n In agreement with Table 49, this corresponds in turn to 49-1-49-72 of Table 49, representing the compound numbers 52-1-52-72 in turn.
Table 53: in the general formula I-1E, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n In agreement with Table 49, corresponding in turn to 49-1-49-72 of Table 49, represent the compound numbers 53-1-53-72 in turn.
Table 54: in the general formula I-1E, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n In agreement with Table 49, this corresponds in turn to 49-1-49-72 of Table 49, representing the compound numbers 54-1-54-72 in turn.
Table 55: in the general formula I-1E, when R is 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding in sequence to 49-1-49-72 of Table 49, in accordance with Table 49, represents the compound numbers 55-1-55-72 in sequence.
Table 56: in the general formula I-1E, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n In agreement with Table 49, this corresponds in turn to 49-1-49-72 of Table 49 and represents the compound numbers 56-1-56-72 in turn.
Table 57: in the general formula I-1E, when R 1 ＝CH 3 、R 2 (= Cl), substituent (R) 4 ) n In agreement with Table 49, corresponding in turn to 49-1-49-72 of Table 49, represent the compound numbers 57-1-57-72 in turn.
TABLE 57-1: in the general formula I-1E, when R 1 ＝CH 3 、R 2 When = F, substituent (R) 4 ) n In agreement with Table 49, corresponding in turn to 49-1-49-72 of Table 49, represent the compound numbers 57-1-57-1-72 in turn.
Table 58: in the general formula I-1E, when R 1 ＝C 2 H 5 、R 2 (= Cl), substituent (R) 4 ) n In agreement with Table 49, this corresponds in turn to 49-1-49-72 of Table 49, representing the compound numbers 58-1-58-72 in turn.
TABLE 58-1: in the general formula I-1E, when R is 1 ＝C 2 H 5 、R 2 When = F, substituent (R) 4 ) n In agreement with Table 49, this corresponds in turn to 49-1-49-72 of Table 49, representing the compound numbers 58-1-58-1-72 in turn.
Table 59: in the general formula I-1E, when R is 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n In agreement with Table 49, corresponding in turn to 49-1-49-72 of Table 49, represents the compound numbers 59-1-59-72 in turn.
Table 59-1: in the general formula I-1E, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n In agreement with Table 49, this corresponds in turn to 49-1-49-72 of Table 49, representing a compound number of 59-1-59-1-72 in turn.
In the general formula I-1F, some of the compounds of the present invention are represented by the compounds shown in tables 60 to 70;
Figure BDA0002747185910000222
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 60, and represent the numbers of the compounds which are 60-1 to 60-68 in sequence.
Watch 60
No. (R 4 )n No. (R 4 )n No. (R 4 )n
60-1 — 60-2 5-CO 2 C 2 H 5 60-3 4-Cl-5-NO 2
60-4 4-F 60-5 5-CO 2 C(CH 3 ) 60-6 4-Cl-5-CN
60-7 4-Cl 60-8 5-CHO 60-9 4-Cl-5-CH 3
60-10 4-CN 60-11 5-NH 2 60-12 4-Cl-6-CH 3
60-13 4-NO 2 60-14 5-CONH 2 60-15 4-Cl-6-CH(CH 3 ) 2
60-16 4-CH 3 60-17 5-CONHCH 3 60-18 4-Cl-5-CF 3
60-19 4-CF 3 60-20 5-CONHC 2 H 5 60-21 4-Cl-5-OCH 3
60-22 4-OCH 3 60-23 5-CONHCH(CH 3 ) 2 60-24 4-Cl-6-OCH 3
60-25 4-SCH 3 60-26 5-CSNH 2 60-27 4-Cl-5-CO 2 CH 3
60-28 4-NH 2 60-29 5-CSNHCH 3 60-30 4-Cl-5-CONHCH 3
60-31 5-Cl 60-32 4-F-5-Cl 60-33 4-CN-6-CH 3
60-34 5-Br 60-35 4-Cl-5-F 60-36 4,6-2CH 3
60-37 5-I 60-38 4,5-2Cl 60-39 4-CH 3 -5-CO 2 C 2 H 5
60-40 5-CN 60-41 4,6-2Cl 60-42 4-CH 3 -5-CO 2 H
60-43 5-C 2 H 5 60-44 4-Cl-5-Br 60-45 4-CH 3 -5-CONH 2
60-46 5-CH 2 CH 2 CH 3 60-47 4-Cl-5-I 60-48 4-C(CH 3 ) 3 -6-CF 3
60-49 5-CO 2 CH 3 60-50 4,6-2Br 60-51 4-CF 3 -5-CO 2 CH 3
60-52 4-CF 3 -5-CO 2 C 2 H 5 60-53 4-CO 2 CH 3 -6-CH 3 60-54 4,6-2Cl-5-Br
60-55 4-CF 3 -5-CONH 2 60-56 4-CO 2 C 2 H 5 -6-CH 3 60-57 4,5-2Cl-6-CH 3
60-58 4-OCH 3 -5-Br 60-59 5-CO 2 C 2 H 5 -6-CH 3 60-60 4,6-2Cl-5-CHO
60-61 4,6-2OCH 3 60-62 4-N(CH 3 ) 2 -5-F 60-63 4-Cl-5-NO 2 -6-CH 3
60-64 4-CO 2 CH 3 -6-Cl 60-65 4,6-2F-5-Cl 60-66 4-Cl-5-NO 2 --6-CO 2 C 2 H 5
60-67 4-CO 2 C 2 H 5 -6-Cl 60-68 4,6-2F-5-Br
Table 61: in the general formula I-1F, when R 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding to Table 60 in the order of 60-1 to 60-68, the numbers of the representative compounds are in the order of 61-1 to 60-68.
Table 62: in the general formula I-1F, when R 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n Corresponding to Table 60 in the order 60-1 to 60-68, the compound numbers are 62-1 to 62-68 in the order.
Table 63: in the general formula I-1F, when R is 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n Corresponding to Table 60 in sequence from 60-1 to 60-68 of Table 60, the numbers of the representative compounds are in sequence from 63-1 to 63-68.
Table 64: in the general formula I-1F, when R 1 ＝Cl、R 2 When = Br, substituent (R) 4 ) n Corresponding to Table 60 in sequence from 60-1 to 60-68 of Table 60, the numbers of the representative compounds are in sequence from 64-1 to 64-68.
Table 65: in the general formula I-1F, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to Table 60 in turn, 60-1 to 60-68 in Table 60 represent compounds having numbers in turn 65-1 to 65-68.
Table 66: in the general formula I-1F, when R 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding to Table 60 in turn from 60-1 to 60-68 of Table 60, represent compoundsThe numbers are 66-1-66-68 in sequence.
Table 67: in the general formula I-1F, when R 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to Table 60 in turn, 60-1 to 60-68 in Table 60 represent the compound numbers 67-1 to 67-68 in turn.
Table 68: in the general formula I-1F, when R is 1 ＝CH 3 、R 2 (= Cl), substituent (R) 4 ) n Corresponding to Table 60 in turn to 60-1 to 60-68 in Table 60, the numbers of the representative compounds are in turn 68-1 to 68-68.
Table 68-1: in the general formula I-1F, when R is 1 ＝CH 3 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 60 in turn, 60-1 to 60-68 in Table 60 represent the numbers of the compounds in turn 68-1-1 to 68.
Table 69: in the general formula I-1F, when R 1 ＝C 2 H 5 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 60 in sequence from 60-1 to 60-68 of Table 60, the numbers of the representative compounds are 69-1 to 69-68 in sequence.
TABLE 69-1: in the general formula I-1F, when R 1 ＝C 2 H 5 、R 2 (= F), substituent (R) 4 ) n Corresponding to Table 60 in turn to 60-1-60-68 in Table 60, the numbers of the representative compounds are 69-1-69-1-68 in turn.
Table 70: in the general formula I-1F, when R 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 60 in turn, 60-1 to 60-68 in Table 60 represent the compound numbers 70-1 to 70-68 in turn.
TABLE 70-1: in the general formula I-1F, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 60 in turn to 60-1 to 60-68 in Table 60, the numbers of the representative compounds are 70-1-1 to 70-1 to 68 in turn.
In the general formula I-1G, some of the compounds of the present invention are represented by the compounds shown in tables 71 to 81;
Figure BDA0002747185910000241
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 71, and represent the compound numbers 71-1-71-36 in sequence.
Watch 71
No. (R 4 )n No. (R 4 )n No. (R 4 )n
71-1 — 71-2 6-CO2CH3 71-3 6-CON(CH 3 ) 2
71-4 6-Cl 71-5 6-CO2C2H5 71-6 6-CON(C 2 H 5 ) 2
71-7 6-Br 71-8 6-CO2C(CH3)3 71-9 6-CSNH 2
71-10 6-CN 71-11 6-CO2H 71-12 6-CSNHCH 3
71-13 6-CH 3 71-14 6-NH2 71-15 4-F-6-CN
71-16 6-OCH 3 7117 6-N(CH3)2 71-18 4-F-6-CO 2 CH 3
71-19 6-SCH 3 71-20 6-CONH2 71-21 4-F-6-CONHCH 3
71-22 6-SOCH 3 71-23 6-CONHCH3 71-24 4-Cl-5-NHCOCH 3
71-25 6-SO 2 CH 3 71-26 6-CONHC2H5 71-27 4-Cl-6-CN
71-28 4-Cl-6-CO 2 CH 3 71-29 4-Br-6-CN 71-30 4-CH 3 -6-CN
71-31 4-Cl-6-CONHCH 3 71-32 4-Br-6-CO 2 CH 3 71-33 4-CH 3 -6-CO 2 CH 3
71-34 5,6-2Cl 71-35 4-Br-6-CONHCH 3 71-36 4-CH 3 -6-CONHCH 3
Table 72: in the general formula I-1G, when R is 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1 to 71-36 of Table 71, representing compounds numbered in turn 72-1 to 72-36.
Table 73: in the general formula I-1G, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n Corresponding to Table 71 in turn to 71-1-71-36 of Table 71, the representative compound numbers are 73-1-73-36 in turn.
Table 74: in the general formula I-1G, when R is 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1-71-36 of Table 71, the compound numbers are 74-1-74-36 in turn.
Table 75: in the general formula I-1G, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1 to 71-36 of Table 71, the representative compound numbers are 75-1 to 75-36 in turn.
Table 76: in the general formula I-1G, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to Table 71 in turn to 71-1 to 71-36 in Table 71, the numbers of the representative compounds are 76-1 to 76-36 in turn.
Table 77: in the general formula I-1G, when R 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding to Table 71 in turn to 71-1 to 71-36 in Table 71, the representative compound numbers are in turn 77-1 to 77-36.
Table 78: in the general formula I-1G, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to 71-1-71-36 in Table 71 in sequence, and representing the compound numbers 78-1-78-36 in sequence。
Table 79: in the general formula I-1G, when R is 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1-71-36 in Table 71, the numbers of the representative compounds are 79-1-79-36 in turn.
TABLE 79-1: in the general formula I-1G, when R is 1 ＝CH 3 、R 2 (= F), substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1-71-36 in Table 71, the numbers of the representative compounds are 79-1-1-79-1-36 in turn.
Table 80: in the general formula I-1G, when R is 1 ＝C 2 H 5 、R 2 (= Cl), substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1 to 71-36 in Table 71, the numbers of the representative compounds are in turn 80-1 to 80-36.
TABLE 80-1: in the general formula I-1G, when R is 1 ＝C 2 H 5 、R 2 (= F), substituent (R) 4 ) n Corresponding to 71-1-71-36 in Table 71 in turn in accordance with Table 71, the numbers of the representative compounds are 80-1-1-80-1-36 in turn.
Table 81: in the general formula I-1G, when R is 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1 to 71-36 in Table 71, the numbers of the representative compounds are 81-1 to 81-36 in turn.
TABLE 81-1: in the general formula I-1G, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 71 in turn to 71-1-71-36 in Table 71, the numbers of the representative compounds are 81-1-1-81-1-36 in turn.
In the general formula I-1H, some of the compounds of the present invention are represented by the compounds shown in tables 82 to 92;
Figure BDA0002747185910000251
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 82, and the numbers of the representative compounds are as followsThe times are 82-1-82-36.
Table 82
No. (R 4 )n No. (R 4 )n No. (R 4 )n
82-1 — 82-2 6-CO2CH3 82-3 6-CON(CH 3 ) 2
82-4 3-Cl 82-5 6-CO2C2H5 82-6 6-CON(C 2 H 5 ) 2
82-7 6-Cl 82-8 6-CO2C(CH3)3 82-9 6-CSNH 2
82-10 6-CN 82-11 6-CO2H 82-12 6-CSNHCH 3
82-13 6-CH 3 82-14 6-NH2 82-15 5-F-6-CN
82-16 6-OCH 3 82-17 6-N(CH3)2 82-18 5-F-6-CO 2 CH 3
82-19 6-SCH 3 82-20 6-CONH2 82-21 5-F-6-CONHCH 3
82-22 6-SOCH 3 82-23 6-CONHCH3 82-24 5-Cl-5-NHCOCH 3
82-25 6-SO 2 CH 3 82-26 6-CONHC2H5 82-27 5-Cl-6-CN
82-28 5-Cl-6-CO 2 CH 3 82-29 5-Br-6-CN 82-30 5-CH 3 -6-CN
82-31 5-Cl-6-CONHCH 3 82-32 5-Br-6-CO 2 CH 3 82-33 5-CH 3 -6-CO 2 CH 3
82-34 5,6-2Cl 82-35 5-Br-6-CONHCH 3 82-36 5-CH 3 -6-CONHCH 3
Table 83: in the general formula I-1H, when R is 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding to Table 82 in turn, 82-1 to 82-36 in Table 82 represent compounds having the numbers 83-1 to 83-36 in turn.
Table 84: in the general formula I-1H, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n In agreement with Table 82, this corresponds in turn to 82-1-82-36 of Table 82, representing a compound number in turn 84-1-84-36.
Table 85: in the general formula I-1H, when R is 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n In agreement with Table 82, the numbers of the representative compounds, which correspond in turn to 82-1 to 82-36 of Table 82, are in turn 85-1 to 85-36.
Table 86: in the general formula I-1H, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding in sequence to Table 82 from 82-1 to 82-36 of Table 82, and representing a compound number of 86-1 to 86-36 in sequence.
Table 87: in the general formula I-1H, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to Table 82 in turn, 82-1 to 82-36 in Table 82 indicate that the numbers of the compounds are 87-1 to 87-36 in turn.
Table 88: in the general formula I-1H, when R is 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding in sequence to Table 82, 82-1-82-36 of Table 82, represents compound numbers 88-1-88-36 in sequence.
Table 89: in the general formula I-1H, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n In agreement with Table 82, the numbers of the representative compounds, which correspond in turn to 82-1 to 82-36 of Table 82, are 89-1 to 89-36.
Table 90: in the general formula I-1H, when R is 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 82 in turn, 82-1 to 82-36 in Table 82 represent compounds having the numbers 90-1 to 90-36 in turn.
TABLE 90-1: in the general formula I-1H, when R 1 ＝CH 3 、R 2 (= F), substituent (R) 4 ) n Corresponding to 82-1-82-36 in Table 82 in turn, the numbers of the representative compounds are 90-1-90-1-36 in turn.
Table 91: in the general formula I-1H, when R is 1 ＝C 2 H 5 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 82 in turn, 82-1 to 82-36 in Table 82 represent the numbers of the compounds in turn 91-1 to 91-36.
TABLE 91-1: in the general formula I-1H, when R 1 ＝C 2 H 5 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 82 in turn, 82-1 to 82-36 in Table 82 represent the numbers of the compounds in turn 91-1-1 to 91-1 to 36.
Table 92: in the general formula I-1H, when R is 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 82 in turn, 82-1 to 82-36 of Table 82 indicate that the compound numbers are in turn 92-1 to 92-36.
TABLE 92-1: in the general formula I-1H, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 82 in turn, 82-1-82-36 in Table 82 represents the number of the compound in turn 92-1-92-1-36.
In the general formula I-1I, some of the compounds of the present invention are represented by the compounds shown in tables 93 to 103;
Figure BDA0002747185910000261
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 93, and represent the compound numbers 93-1-93-24 in sequence.
Watch 93
No. (R 4 )n No. (R 4 )n No. (R 4 )n
93-1 5-F-6-CN 93-2 5-Br-6-CO 2 CH 3 93-3 6-CO 2 CH 3
93-4 5-Cl-6-CN 93-5 5-F-6-CONHCH 3 93-6 6-CO 2 H
93-7 5-Br-6-CN 93-8 5-Cl-6-CONHCH 3 93-9 6-CONH 2
93-10 5-CH 3 -6-CN 93-11 5-Br-6-CONHCH 3 93-12 6-CONHCH 3
93-13 5-F-6-CO 2 CH 3 93-14 5-CH 3 -6-CO 2 CH 3 93-15 6-CONHC 2 H 5
93-16 5-Cl-6-CO 2 CH 3 93-17 6-CN 93-18 6-CON(CH 3 ) 2
93-19 6-CON(C 2 H 5 ) 2 93-20 6-CSNHCH 3 93-21 6-CSN(CH 3 ) 2
93-22 6-CSNH 2 93-23 6-CSNHC 2 H 5 93-24 6-CSN(C 2 H 5 ) 2
Table 94: in the general formula I-1I, when R is 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n In agreement with Table 93, corresponding in turn to 93-1 to 93-24 of Table 93, the representative compound numbers are in turn 94-1 to 94-24.
Table 95: in the general formula I-1I, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n In agreement with Table 93, corresponding in turn to 93-1 to 93-24 of Table 93, the representative compound numbers are, in turn, 95-1 to 95-24.
Table 96: in the general formula I-1I, when R 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n In agreement with Table 93, corresponding in turn to 93-1 to 93-24 of Table 93, the representative compound numbers are in turn 96-1 to 96-24.
Table 97: in the general formula I-1I, when R 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding to Table 93 in turn, corresponding to 93-1 to 93-24 in Table 93, the numbers of the representative compounds are 97-1 to 97-24 in turn.
Table 98: in the general formula I-1I, when R 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n In agreement with Table 93, corresponding in turn to 93-1 to 93-24 of Table 93, represent the compound numbers 98-1 to 98-24 in turn.
TABLE 99: in the general formula I-1I, when R is 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n In agreement with Table 93, corresponding in turn to 93-1 to 93-24 of Table 93, represent the compound numbers 99-1 to 99-24 in turn.
Table 100: in the general formula I-1I, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to Table 93 in sequence from 93-1 to 93-24 of Table 93, representing compound numbers from 100-1 to 100-24 in sequence.
Table 101: in the general formula I-1I, when R is 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n In agreement with Table 93, corresponding in sequence to 93-1 to 93-24 of Table 93, the representative compound numbers are in sequence 101-1 to 101-24.
TABLE 101-1: in the general formula I-1I, when R is 1 ＝CH 3 、R 2 When = F, substituent (R) 4 ) n In agreement with Table 93, corresponding in turn to 93-1-93-24 of Table 93, the representative compound numbers are in turn 101-1-1-101-1-24.
Table 102: in the general formula I-1I, when R is 1 ＝C 2 H 5 、R 2 When = Cl, substituent (R) 4 ) n In agreement with Table 93, corresponding in turn to 93-1 to 93-24 of Table 93, represent the compound numbers 102-1 to 102-24 in turn.
TABLE 102-1: in the general formula I-1I, when R is 1 ＝C 2 H 5 、R 2 When = F, substituent (R) 4 ) n In agreement with Table 93, corresponding in turn to 93-1-93-24 of Table 93, represents the compound numbers 102-1-102-1-24 in turn.
Table 103: in the general formula I-1I, when R is 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding in sequence to Table 93 in tables 93 and 93-1-93-24, representing compound numbers in sequence 103-1-103-24.
Table 103-1: in the general formula I-1I, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n In agreement with Table 93, corresponding in turn to 93-1-93-24 of Table 93, the representative compound numbers are in turn 103-1-103-1-24.
In the general formula I-1J, some of the compounds of the present invention are represented by the compounds shown in tables 104 to 114;
Figure BDA0002747185910000271
when R is 1 ＝Cl、R 2 ＝CH 3 When (R) 4 ) n The substituents are shown in Table 104, and represent the compound number of 104-1-104-40。
Table 104
No. (R 4 )n No. (R 4 )n No. (R 4 )n
104-1 4-Cl 104-2 4-OCH 3 -6-NHCH 3 104-3 4-N(CH 3 ) 2
104-4 4-CN 104-5 4,6-2SCH 3 104-6 4-NH 2 -6-Cl
104-7 4-SCH 3 104-8 4-SCH 3 -6-Cl 104-9 4-NH 2 -6-OCH 3
104-10 4-SOCH 3 104-11 4-SCH 3 -6-NHCH 3 104-12 4-NH 2 -6-SCH 3
104-13 4-SO 2 CH 3 104-14 4-SOCH 3 -6-Cl 104-15 4-NH 2 -6-SOCH 3
104-16 4,6-2Cl 104-17 4-SO 2 CH 3 -6-Cl 104-18 4-NH 2 -6-SO 2 CH 3
104-19 4-CN-6-Cl 104-20 4-NHCOCH 3 -6-Cl 104-21 4-NH-i-Pr-6-Cl
104-22 4,6-2CH 3 104-23 4-NHCOCH 3 -6-OCH 3 104-24 4-NH-i-Pr-6-CN
104-25 4,6-2OCH 3 104-26 4-NHCOCH 3 -6-SCH 3 104-27 4-NH-i-Pr-6-OCH 3
104-28 4-OCH 3 -6-Cl 104-29 4-NHCOCH 3 -6-SO 2 CH 3 104-30 4-NH-i-Pr-6-SCH 3
104-31 4-NH-i-Pr-6-NHCOCH 3 104-32 4-NH-t-Bu-6-CN 104-33 4-NH-t-Bu-6-NH 2
104-34 4-NH-i-Pr-6-NH 2 104-35 4-NH-t-Bu-6-OCH 3 104-36 4-NH-t-Bu-6-NHCH 3
104-37 4-NH-i-Pr-6-NHCH 3 104-38 4-NH-t-Bu-6-SCH 3 104-39 4-NH-t-Bu-6-NHCOCH 3
104-40 4-NH-t-Bu-6-Cl
Table 105: in the general formula I-1J, when R is 1 ＝Cl、R 2 When = COOH, substituent (R) 4 ) n Corresponding to Table 104 in this order to 104-1 to 104-40 of Table 104, the compound numbers are in this order 105-1 to 105-40.
Table 106: in the general formula I-1J, when R is 1 ＝Cl、R 2 ＝OCH 3 When (R) is substituted 4 ) n Corresponding to Table 104 in sequence from 104-1 to 104-40 of Table 104, representing compounds numbered in sequence from 106-1 to 106-40.
Table 107: in the general formula I-1J, when R is 1 ＝Cl、R 2 When = CHO, substituent (R) 4 ) n Corresponding to Table 104 in the order of 104-1 to 104-40 in Table 104, the compound numbers are 107 in the order of-1—107-40。
Table 108: in the general formula I-1J, when R is 1 ＝Cl、R 2 When not less than Br, a substituent (R) 4 ) n Corresponding to Table 104 in this order to 104-1 to 104-40 of Table 104, representing compounds having the number of 108-1 to 108-40 in this order.
Table 109: in the general formula I-1J, when R is 1 ＝Cl、R 2 ＝NH 2 When (R) is substituted 4 ) n Corresponding to Table 104 in this order to 104-1 to 104-40 of Table 104, the compound numbers are in this order 109-1 to 109-40.
Table 110: in the general formula I-1J, when R is 1 ＝Cl、R 2 ＝NO 2 When (R) is substituted 4 ) n Corresponding to Table 104 in this order to 104-1 to 104-40 of Table 104, the compound numbers are in this order 110-1 to 110-40.
Table 111: in the general formula I-1J, when R is 1 ＝Cl、R 2 When =4-Br-Ph, substituent (R) 4 ) n Corresponding to Table 104 in this order to 104-1 to 104-40 in Table 104, the compound numbers are in this order 111-1 to 111-40.
Table 112: in the general formula I-1J, when R 1 ＝CH 3 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 104 in the order of 104-1 to 104-40 in Table 104, the compound numbers are 112-1 to 112-40 in the order of.
TABLE 112-1: in the general formula I-1J, when R is 1 ＝CH 3 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 104 in turn to 104-1-104-40 of Table 104, the compound numbers are in turn 112-1-112-1-40.
Table 113: in the general formula I-1J, when R is 1 ＝C 2 H 5 、R 2 (= Cl), substituent (R) 4 ) n Corresponding to Table 104 in turn to 104-1 to 104-40 in Table 104, the compound numbers are in turn 113-1 to 113-40.
TABLE 113-1: in the general formula I-1J, when R is 1 ＝C 2 H 5 、R 2 When = F, substituent (R) 4 ) n Corresponding to the table 104 in turn104-1 to 104-40, the number of the compound is 113-1-1 to 113-1-40 in sequence.
Table 114: in the general formula I-1J, when R is 1 ＝CHF 2 、R 2 When = Cl, substituent (R) 4 ) n Corresponding to Table 104 in the order of 104-1 to 104-40 in Table 104, the compound numbers are in the order of 114-1 to 114-40.
Table 114-1: in the general formula I-1J, when R is 1 ＝CHF 2 、R 2 When = F, substituent (R) 4 ) n Corresponding to Table 104 in turn to 104-1-104-40 of Table 104, the compound numbers are in turn 114-1-114-1-40.
The compounds of the invention are prepared according to the following process, the reaction scheme being as follows, wherein the groups are as defined above unless otherwise stated:
the preparation of the compounds of the general formula I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H and I-1I, I-1J is carried out by the following methods:
Figure BDA0002747185910000281
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Figure BDA0002747185910000291
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Figure BDA0002747185910000301
the intermediate I1 reacts with II-1, II-2, II-3, II-4, II-5, II-6, II-7, II-8, II-9 and II-10 respectively under alkaline conditions in a proper solvent to obtain the compounds with the general formulas I-1A, I-1B, I-1C, I-1D, I-1E, I-1F, I-1G, I-1H, I-1I and I-1J.
Suitable bases can be selected from, for example, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, triethylamine, pyridine, sodium methoxide, sodium ethoxide, sodium hydride, potassium or sodium tert-butoxide, etc.
The reaction is carried out in a suitable solvent, which may be selected from, for example, tetrahydrofuran, 1,4-dioxane, acetonitrile, toluene, xylene, benzene, N-dimethylformamide, N-methylpyrrolidone, dimethylsulfoxide, acetone, or butanone.
The reaction temperature may be between room temperature and the boiling temperature of the solvent, and is generally from 20 to 100 ℃.
The reaction time is from 30 minutes to 20 hours, usually from 1 to 10 hours.
The intermediate I1 is partially commercially available and can be prepared by known methods, for example, by the methods described in documents JP2000007662, US4977264, US6090815, US20040092402, JP09124613, US5468751, US4985426, US4845097, journal of the American Chemical Society (1957), 79,1455, journal of Chemical Society (1955), p.3478-3481.
Intermediates II-1 to II-10 are key intermediates for the preparation of the compounds of the general formula I-1 according to the invention, and are prepared as follows:
Figure BDA0002747185910000302
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Figure BDA0002747185910000311
/>
Figure BDA0002747185910000321
intermediates M1 to M10 are reacted with 4-Boc-aminopiperidine, respectively, at a suitable temperature, DMF as solvent and potassium carbonate as acid-binding agent for 30 minutes to 10 hours, usually 1 to 4 hours, to give intermediates N1 to N10, according to the procedure of Journal of combinatorial Chemistry,10 (2), 225 to 229;2008 and WO2008065508; n1 to N10 were Boc-removed to give intermediates II-1 to II-10, respectively, according to Bioorganic & Medicinal Chemistry Letters,20 (2), 746-754;2010 and WO2012112743.
Although the compounds of the general formula I of the present invention also belong to the class of pyrimidine-containing piperidinamines as well as certain compounds disclosed in the prior art, the structural features still differ. And due to the structural difference, the compound of the invention has better bactericidal and insecticidal and acaricidal activity.
The compound of the general formula I shows excellent activity on various germs in agriculture or other fields, and also shows better activity on pests and mites. 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 agriculture or other fields.
The examples of diseases 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.; <xnotran> , ( , , , , , , , , , , , , , , , ), ( , , , , , , ), ( , , , , ), ( , , , , , , 5363 zxft 5363 , , , , , , , , , , ), ( , , , , ), ( , , ), ( , , , , , , , ), ( , , , , , , , , , ), ( , </xnotran> Black spot of rape, black spot of sesame, black spot of sunflower, black spot of castor, black spot of tomato, black spot of pepper, black spot of eggplant, black spot of bean, black spot of cucumber, black spot of celery, black rot of carrot, black spot of apple, black spot of peanut), 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 northern leaf blight, kenaf waist break disease, rice blast, black sheath blight, sugarcane eye spot disease, cotton boll aspergillosis, peanut crown rot, soybean stem blight, soybean black spot disease, melon northern leaf spot disease, peanut net spot disease, tea red leaf spot disease, pepper white spot disease, wax gourd leaf spot disease, celery black rot disease, spinach heart rot, kenaf leaf mold, kenaf spot disease, jute stem spot disease, soybean purple spot disease, sesame leaf spot disease, castor gray spot disease, tea brown leaf spot disease, brown speck disease, kidney bean red spot disease, bitter gourd white spot disease, watermelon spot disease, jute rot disease, sunflower root 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, etc.); 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 column smut, kernel smut, sugarcane head smut, 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.
The compounds of the formula I can be used for controlling the following pests:
coleoptera (Coleoptera) (beetle): leguminous species (Acanthoscelides spp.) (elephant), phaseolus vulgaris (Acanthoscelides obtectus) (common pisiform image), ceratophyllum album (Agrilus planipes) (Fraxinus variegatus) and Flammulina species (Agriotes spp.) (wireworm), anoplophora glabripennis (Asian longhorn longipedunculus), gothistle species (Anthonium spp.) (Arthobium family), gothistle (Anthonium grandis) (Cotton bollworm cocoon), apium mellea species (Aphidius spp.) (Aprionus spp.) (Anthonium spp.) (elephant), aconitum species (Apocynia spp.) (Holotrichia grub) black striped tortoise (atacinia pretzeriana), cryptogamic beet (atomys specularis), cryptogamic beet (atomura lineris) (small beet beetles (pygmy mangold beetles), cucurbita species (autolophore spp.), weevils (botynoderes punctinvaris) (beetroot weevils), pisiform species (Bruchus spp.) (weevils), pisiform weevils (Bruchus pisum) (pea weevils), cacosesia species (cacosesia spp.), pisum variegatus (callosoides maculoides) (southern cowpea weevils), yellow tail beetles (carpophillius hemiptera) (xerophycus ceras), beet beetles (casssida viteta), longipes (costa spp.), ccorooma species (Ccorooma spp.) (Jin Dichong (chrysomycis)), diabrotica (Cerotoma trifur cata) (Bulbophyllum tenesmus), costus species (Ceratorchus spp.) (weevil)), chinese cabbage weevil (Ceratophycus assimilis) (cabbage weevil), chinese cabbage weevil (cabbage seed weevil)), chinese cabbage weevil (Ceratophycus napus napi) (cabbage Curculio), genus flea species (Chaetocnema spp.) (Jin Dichong), genus Colaspis species (Colaspis spp.) (beetle), conoderus scalaris, conoderus stigmosus, li Xiang (Conotrachulus neupharer) (Mei Zhui weevil), cotinus nitidis (greenflies June beetle), asparagus caterpillars (Crioceris aspalatus) (asparagus beetle), red beetles (cryptolepis ferrugineus) (rust Gu Jiachong), long horn beetles (cricotulis pusillus) (flat beetle), pseudopteris ferrugineus (cryptolepis ferrugineus) (turkey Gu Jiachong (turnbuckle beetle)), encochlamya species (Ctenoceps spp.) (nematode), elephant species (curriculus spp.) (ostrich), ostrinia species (ostrich spp. (ostrich), ostrinia spp. (ostrinia nubila spp.) (grub), white beetle larvae (sylvestris spp.) (ostrinia nigripes (ostrich), ostrinia nigrum spilus spp. (ostrinia spp.) (grub) (leucopteris), ostrinia nigrum (ostrinia nigrum spp.) (ostrinia fusca (ostrinia nigrum spp.) (grub) (leucopteris 26), ostrinia septemia spp (ostrinia septemia spp.) (ostrinia september) (ostrinia septemia spp. (ostrinia september) (sarum) <xnotran> (raustinus cubae), (Hylobius pales) ( (pales weevil)), 3238 zxft 3238 (Hypera spp.) (), (Hyperapostica) ( ), hyperdoes (Hyperdoes spp.) ( (Hyperodes weevil)), (Hypothenemus hampei) ( ), (Ips spp.) ( (engravers)), (Lasioderma serricorne) ( ), (Leptinotarsa decemlineata) ( ), liogenys fuscus, liogenys suturalis, (Lissorhoptrus oryzophilus) ( ), (Lyctus spp.) ( / (powder post beetles)), maecolaspisjoliveti, megascelis (Megascelis spp.), (Melanotus communis), (Meligethes spp.), (Meligethes aeneus) ( (blossombeetle)), (Melolontha melolontha) ( ), oberea brevis, (Oberea linearis), (Oryctes rhinoceros) ( (date palm beetle)), (Oryzaephilus mercator) ( (merchant grain beetle)), (Oryzaephilus surinamensis) ( 3262 zxft 3262 (sawtoothcd grain bcctlc)), </xnotran> Weevil species (rotirrhynchus spp.) (weevil), black angle negative mudworm (Oulema melanopus) (orange foot negative mudworm (cereal leaf beetle)), rice negative mudworm (Oulema oryzae), rose short beak weevil species (pantomomus spp.) (weevil), phyllopodium species (Phyllophaga spp.) (pentacle/hexacle chafer), phvllophaga cuyabana, phyllotreta spp. (Jin Dichong), pinus horrida spp. (Phynchites spp.), popiliajaponica (Popiliajaponica) (Japanese chafer), stachys palustris (Prostephanis truncates) (large palustris), gu Chun (Rhizoperta dominica) (Gu Xiao moth (leiser grandis borer)), rhizopus spp. (Rhizogus grandis spp.) (European gold (European chafer)), cryptocarya spp. (Pharma purpurea), rhynchophora spp. (Pharma purpurea), rhynchophorus spp. (elephant), leptophora, rhynchophorus spp.) (Phyllophora spp.) (Rhynchophorus spp.) (elephant) clods (stupid moth) species, species of genus shonophorus (Scolytus spp.) (elephant), elephant (sitonas linatus) (pea She Xiangjia (pca leaf weevil)), elephant species (Sitophilus spp.) (elephant nail), elephant (Sitophilus grandis) (maggot worm (gruney weevil)), rice weevil (Sitophilus oryzae) (rice weevil), stewartia (Stegobium panicum) (drumstick beetle), pseudogriseus sper (Tribolium spp.) (elephant worm) Red pseudo-grain theft (Tribolium castaneum), tribolium contusium (conjugated flowable), gordonia variegata (trodogerma variabile) (warehouse bark mortar) and Zabrus tenboiides.
Dermaptera (Dcrmaptcra) (earwigs).
Vein winged order (Dictyoptera) (cockroach): german cockroach (Blattella germanica) (German cockroach), blattaria orientalis (Blatta orientalis), blatta palustris (Blatta cockroach), blatta americana (Periplaneta americana), blatta australiana (Blatta australiana), blatta brown cockroach (pcriparian cockroach), blatta smokaria (Periplaneta fuliginosa) (Blatta nigricana), blatta nigricans (cockroach), and Blatta nigricans (blattria nigricana), and Blatta canata (brown cockroach), blatta fula nigra (Blattella germanica) and Blatta (Blattella germanica) are provided.
Diptera (Diptera) (flies): aedes species (Aedes spp.) (mosquito), lucerne fly larvae (Agromyza frontella) (alfalfa blossom flies), agromyzis species ((Agromyza spp.) (leaf flies), trypetid species (Anastrepha spp.) (fruit flies), garlerthan trypetid flies (Anastrepha persica) (garlerthan trypetid flies), anopheles species (Anopheles spp.) (mosquito), fruit fly species (Bactrocera spp.) (fruit flies), melon flies (Bactrocera cubae) (melon flies), citrus fruit flies (Bactrocera dorsalis) (citrus fruit flies), small-stick fly species (ceitis spp.) (fruit flies), and sea fly larvae (sea fly) (sea flies). Deer fly species (Chrysops spp.), conomyiis species (Cochliomyia spp.), lepis larva (Calla indica), mosquito species (Contarinia spp.) ( mosquito), culex species (Culex spp.) (mosquito), she mosquito species (Dasineura spp.) ( mosquito), oil leaf mosquito (Dasineurabasic) (cabbage mosquito), seed fly species (Delia spp.), ground fly (Delia platura) (root maggot (Seedcorn maggo), fruit fly species (Drosophila spp.) (vinegar), seed species (Fannula spp.) (Musca. Sp.) (Familis fly) (3534 fly (Abelix fly) (Fabricius spp.)) (Latif. Sp.) (Latif.) (Latifen) and (Lasiomyza) (Farinia variety) (Farinia spp.) (Fabricius (3534) fly (Latif. Sp.) (Latif The species of Lasiomyza sativa (Musca domestica), gracilliaceae, sargassaceus (Gasterophilus intestialis), gracilliaverearly, haematobia irritans (ceratitis), musca melanogaster (Hylemia spp.) (root maggot), dermomya striata (Hypodema linear) (common dermomya striata), musca maculata (Liriomyza spp.) (leaf miner), musca suda (Liriomyza brassica) (Serpentis melanogaster (serpentine leaf miner)), musca ovis (Melophagus ovis) (sheep tick), musca spps (Musca domestica), and Musca domestica (Musca domestica)) (autumn fly (Musca domestica (Musca), musca domestica (Musca domestica)) (Lasiomyza sativa (Musca), musca domestica (autumn fly (Musca) and Musca domestica) housefly (Vusca domestica) (house fly), sheep fly (Oestrus ovis) (sheep nose fly), european straw fly (Oscinella front) (Sweden straw fly), beet spring fly (Pegomyia beta) (spinach leaf fly (beet leaf), mycoplasma species (Phorbia spp.), carrot stem fly (Psila rosa (carrot rust fly)), cherry fruit fly (Rhagoletis cerasi) (cherry fruit fly), apple fruit fly (Rhagoletis pomoea) (apple bud), rhodoplasma fluvialis (Sitodis malacia mala) (orange wheat fly (orange yellow rice fly)), sheep fly (sheep fly), european straw fly (apple fruit fly (apple leaf fly)), and apple fruit fly (apple fruit fly)) Stable flies (stable flies), horsefly species (horse flies) and mosquito species (mosquito spp.).
Hemiptera (Hemiptera) (stinkbug): stinkbug (Acrosteronum hirae) (green stink bug), america Gu Changchun (Blissus leucopterus) (Long stink bug), potato Juncus nigrus (Calciosa norvegicus) (potato mirid), tropical bug (Cimex hemipterus) (tropical stink bug), bed bug (Cimex molecular) (bed bug), daghertus fasciatus, dichelops furcatus, gottus armyworm (Dysdercus sutureus) (Cotton stinus), edissa meditata, euonymus alatus (Euonymus), euonymus alatus (Brown stinus), euonymus alatus (Brown stink bug), euonymus alatus (Brown stinus)). Apolygus animalis (Helopeltis antani), apolygus sinensis (Helopeltis theivora) (teablight plant bug), apolygus spp (Lagynomus spp.) (stinkbug), oryza sativa (Leptococcus oryzae), oryza heterophylla (Leptococcus variotis), apolygus sacchari (Lygus spp.) (plant bug), apolygus leguminata (Lygus hepsper.) (Lygus bud), apolygus legrinus (Lygus hepsperus hepsus) (western tarnish), apolygus lineolaris (Lygus hesperus), adinus syriacus (Maconellitus hirus hirsutus), neuropus lutescens (Nezara domestica) (southern bug), apostichopus plantula nigra (Phyllostictus), phytopsis strain (Phytopris strain), apostichopus grisea (Phytopsis viridans), phytopsis thalictrus grisea (Phytopus spp.), piezodorus guilidingi, piezococapus lineus (Piecilococcus lineatus) bug, psallus vaccinicola, pseudophyta perseae, scaptocoris castanea and Tradelphia species (Triatoma spp.) (Blodsuctingconense bug)/Nephocorium sutent (kissing bug)).
Homoptera (Homoptera) (aphid, scale, whitefly, leafhopper): <xnotran> (Acrythosiphonpisum) ( (pea aphid)), (Adelges spp.) (adelgids), (Aleurodes proletella) ( ), (Aleurodicus disperses), (Aleurothrixus flccosus) ( (woolly whitefly)), (Aluacaspis spp.), amrasca bigutella bigutella, (Aphrophora spp.) ( (leafhopper)), (Aonidiella aurantii) ( (California red scale)), (Aphis spp.) (), (Aphis gossypii) (cotton aphid), (Aphis pomi) (apple aphid), (Aulacorthitm solani) ( (foxglove aphid)), (Bemisia spp.) (), (Bemisia argentifolii), (Bemisia tabaci) (sweetpotato whitefly), (Brachycolus noxius) ( (Russian aphid)), (Brachycorynclia asparagi) ( (asparagus aphid)), brevennia rehi, (Brevicoryne brassicae) ( ), (Ceroplastes spp.) (), (Ceroplastes rubens) (red wax scale), (Chionaspis spp.) (), (Chrysomphalus spp.) (), </xnotran> <xnotran> (Coccus spp.) (), (Dysaphis plantaginea) (rosy apple aphid), (Empoasca spp.) (), (Eriosoma lanigerum) (woolly apple aphid), (Icerya purchasi) (cottony cushion scale), (Idioscopus nitidulus) (mango leafhopper), (Laodelphax striatellus) (smaller brown planthopper), (Lepidosaphes spp.), (Macrosiphum spp.), (Macrosiphum euphorbiae) ( (potato aphid)), (Macrosiphum granarium) ( (English grain aphid)), (Macrosiphum rosae) ( (rose aphid)), (Macrosteles quadrilineatus) ( (aster leafhopper)), mahanarva frimbiolata, (Metopolophium dirhodum) ( (rose grain aphid)), midis longicornis, (Myzus persicae) ( (green peach aphid)), (Nephotettix spp.) (), (Nephotettix cinctipes) ( (green leafhopper)), (Nilaparvata lugens) (brown planthopper), (Parlatoria pergandii) (chaffscale), (Parlatoria ziziphi) (ebony scale), (Peregrinus maidis) (corn delphacid), </xnotran> Plant species of the genus Laoderma (Philaenus spp.) (Lawsonia inermis), rhizopus viticola (Phyllotreta viticola) (graptophylletra), lepidogra tsugae (Phytopramee) (sport bud scale), lepidogra pellucida (Planococcus spp.) (Lepidogra fargesii), lepidogra (Pseudococcus spp.) (Lepidogra), pseudobagrus pseudococca (Psdococcus brcvis) (pink apple), pyrola peltata (Quadpiditus perus persicus) (Sanjoseph Joscale)), lepidogra (Rhapaphysalum spp.) (Rhapaphytum), and Aphis zeae (Rhalophysalis mai) (maize aphid (corn aphid), rhapaphymatophysa (Rhapaphymatophytid), phytophus aphid major (Rhapaphymatophytid), and Rhapaphymatophymatophytid palea (aphid), rhapathyophyta nikoshidai palusta (Rhapatsu), rhapathys nikoshidai (Rhapatsu), and Rhagophthalmus (maize aphid haplota), rhaphis (maize aphid), rhagophthalmus) are the species lecanicillium (sausetia spp.) (scale), elegans lecanicillium (sausetia oleae) (black scale), schizaphis graminum (Schizaphis graminum) (greenfly), siganus canaliculatus (Sitobion avengense) (british wheat aphid), whitefly (Sogatella furcifera) (white-backed plant), cercosphaera species (Therioaphis spp.) (aphid), ceroplasma species (tomeyyella spp.) (scale), green-house sound species (toxoplasma spp.) (green-house), whitefly species (Trialeurodes vaporariorum) (white-house), white-house whitefly (Trialeurodes vaporariorum) (white-house wing), white-house white-fly (white-house) species (Trialeurodes (whitefly), white-house (white-house) plant (white-house greenfly (white-wing greenfly) The genus Tocopaia (Unaspis spp.) (Lecanis), tocopaia sagina (Unaspis yanonensis) (arrowhead scale) and Zulia entreriana.
Hymenoptera (Hymenoptera) (ants, wasps and bees): species of the genus Oriental Formica (Acromyrmex spp.), sinkiang Blastus (Athalia rosae), she Yishu (Atta spp.) (Ieafcutting ants), species of the genus Blaster (Camponotus spp.) (wooden ants), species of the genus Trichoplusia (Diprion spp.) (wasp.)), species of the genus Formica spp. (Formica spp.) (ants), argentina ant (Iridomymex hugensis) (Argentintinent), species of the genus Pharmacopeia (Monorium spp.) (Monorium minutissima.) (Monorium microphyllum) (Littlet.)), species of the genus Pharmacopeia (Monoorimurinum blanc) (Monoorinian (Solidan faecium virens) (Argentina virens)), (Mongolia phar, melongia virens (Solidax virens)), (Mongolia virens (Solidago virens)), (Mongolian) neoconium species (neodipion spp.) (leaf bees), formica species (pogonormex spp.) (harvested ants), hornet species (Polistes spp.) (wasps), turkey species (Solenopsis spp.) (fire ants), solenopsis sessilis (Tapoinoma sessile) (odorus house (ant)), formica species (tetranomorum spp.) (pavement ant)), wasp species (Veula spp.) (yellow wasp (yellows jack)), and wasp species (Xylocopa spp.) (wasp (carpenter).
Isoptera (Isoptera) (termites): coptotermes spp, qu E termites (Coptotermes curcignatus), france termites (Coptotermes frenchi), coptotermes formosanus (Formosan termite), ceripotermes spp (Cornitomes spp), sand termites spp (Cryptotermes spp) (Nematotermes terreus) and Coptotermes spp (Coptotermes spp)). Heterotermites species (Heterotermites spp.) (desert heterotranspirant termites), chrysanthemum (IIetetermes aureus), wood termites species (Kalottermes spp.) (Nepeter termites), acanthowhite termites species (Incisteriermes spp.) (Nepeter termites), macrotermites species (Macrotermites spp.) (fungus termites), borreria sp. (fungus termites grown termites), bordetella species ((Marginiermes spp.) (Theptotermites) and Bordetella species (Melastoma bateria spp.) (The termites) Serratia species (Microceromes spp.) (grass termites (harvetter termites)), tripterocephalus oryzae (Microtermes obesi), procornierames species (Procornitermes spp.), (subterranean termites), reticulitermes batens, spongilla fructicola (Reticulitermes spp.) (subterranean termites), reticulitermes banyuensis, spongilla fructicola (Reticulitermes grasseei), blastoma lutescens (Reticulitermes flavipes) (Oriental soil termites), blastoma lutescens (Reticulitermes hagei), west Cantonella (Reticulitermes spertus) (West soil termites), sang Tesan termites (Reticulitermes saurus), blastomerus suturensis (Reticulitermes spp.), blastomerus nigripes punctatus (Reticulitermes), blastoma nigritermes termites spilus (Reticulitermes), blastoma termites punctatus (Reticulitermes punctatus), blastoma punctatus (Reticulitermes termes punctatus), blastoma punctatus) Blastus punctatus (North punctatus), blastus punctatus), blastoma punctatus (Reticulitermes termites) and Blastus punctatus) The genus Reticulitermes spp (Schedorrhiotomes spp.) and the genus archaebacteria spp (Zootermopsis spp.) (Pythium species).
Lepidoptera (Lepidoptera) (moths and butterflies): achoeajanata, trichosporon species (Adoxophyes spp.), trichosporon gossypii (Adoxophyes orana), gekko sp (Agrotis spp.), cutworm (Agrotis ipsilon) (Black cutting root worm), trichosta gossypii (Alabama argillacea) (Cotton leaf worm (cotton leaf worm)), amorbia cuneata traniliensis (corn leaf worm), amorbia cuneata, amorphosis tranthientaria (corn leaf worm), anacamptodia depunctata, sporotricharda trichogramma (orange leaf worm) (peach leaf), trichosta florida (European, european cabbage leaf), european cabbage leaf moth (European cabbage leaf moth), european cabbage leaf moth (cabbage leaf moth) (European leaf moth (cabbage leaf moth), european cabbage leaf moth (cabbage leaf moth) (European leaf moth) <xnotran> (Colias spp.), (Conpomorpha cramerella), (Cossus cossus) ( ), (Crambus spp.) (Sod webworms), (Cydia funebrana) ( (plum fruit moth)), (Cydia molesta) ( (oriental fruit moth)), (Cydia nignicana) (pea moth), (Cydia pomonella) ( (codling moth)), darna diducta, (Diaphania spp.) ( (stem borer)), (Diatr aea spp.) ( (stalk bor er)), (Diatraea saccharalis) (sugarcane borer), (Diatraea graniosella) (southwester corn borer), (Earias spp.) (), (Earias insulata) (Egyptian bollworm), (Earias vit.ella) (rough northern bollworm), ecdytopopha aurantianum, (Elasmopalpus lignosellus) (lesser cornstalk borer), (Epiphysias postruttana) (light brown apple moth), (Ephestia spp.) (), (Ephestia cautella) (almond moth), (Ephestia elutella) ( (tobbaco moth)), </xnotran> <xnotran> (Ephestia kuehniella) (Mediterranean flour moth), epimeces (Epimeces spp.), (Epinotia aporema), (Erionota thrax) (banana skipper), (Eupoecilia ambiguella) ( (grape berry moth)), (Euxoa auxiliaris) (army cutworm), (Feltia spp.) (), (Gortyna spp.) (), (Grapholita molesta) ( () (oriental fruit moth)), (Hedylepta indicata) ( (bean leafwebber)), (Helicoverpa spp.) (), (Helicoverpa armigera) (cotton bollworm), (Helicoverpa zea) ( ( /)), (Heliothis spp.) (), (Heliothis virescens) (tobacco budworm), (Hellula undalis) (cabbage webworm), indarbela (Indarbela spp.) ( ), (Keiferia lycopersicella) (tomato pinworm), 8978 zxft 8978 (Leucinodes orbonalis) (eggplant fruit borer), (Leucoptera malifoliella), (Lithocollectis spp.), (Lobesia botrana) (grape fruit moth), </xnotran> Loxagrotis species (Loxagrotis spp.) (Spodoptera exigua), clanis bilineata (Loxagrotis albicostat) (western bean cuprammum), lymantria dispar (Lymantria dispar) (gypsy mols), lyonetia persicae (Lyonetherkelella) (apple leaf moth (apple leaf miner)), oil palm bag moth (Mahansera corbeti) (oil palm bateman), musca species (Malacoma spp.) (tent caterpillers), cabbage looper (Mamestra brassica) (cabbage armyworm (cayram)), bean pod borer (Maruca testulalis) (Bean leaf borer), plutella xylostella (Metaphalia platura), mythimna uniflora (tomato leaf borer), tomato leaf borer (tomato leaf borer) (tomato leaf borer (tomato leaf miner)) (Lymantria, myxobolus) and the like stem borer (Nymphula depunctata) (rice leaf borer (rice case), winter looper (Operphthora briata) (winter moth), european corn borer (Ostrinia nubilalis) (European corn borer (European corn borner)), oxydia vesula, ostrinia clarkii (Pandemia cerana) (common grape leaf moth (common currant torx)), brown apple leaf moth (Pandemia hepariana) (brown apple torx), african mottled butterfly (Papilio demodulus), red Conyza (Pentapora gossypiella) (red cabbage worm (pink bollworm)), asian noctuid species (Perroup. Sp.), rough greenfly (root cutting), brown maize (brown maize greenfly), coffee bean (coffee bean), european corn leaf moth (brown cabbage caterpillar (rice leaf moth) (red cabbage caterpillar (brown cabbage), european noctuid moth (Perfect), european noctui variety (Perroup. Sp.) and Perfect (Rough variety) (Permedia) and Perfect variety (Permedia) and the like, potato tuber moth (Phthalmia opuercula) (potatoo tuber moth), citrus leaf latent moth (Phylocnidis citrella), phylonica spp (Phylonoryces spp.) (leaf miner), cabbage butterfly (Pieri rapae) (imported cabbage worm (insect)), spodoptera frugiperda (Platyphana scabra), indian Gu Bane (Plodia interpunctella) (Indian meal moth), cabbage moth (Plutella xylostella) (diamondback moth), grape berry moth (polychloris virosa) (grape berry moth) (soybean meal moth), orange fruit moth (Prays endocarps), olive leaf moth (Prunus oleaudus) (olive moth), armyworm (Spodoptera), soybean leaf moth (soybean meal moth). Inchworm (Rachiplusia nu), borer (Scorpia incertulas), heliothis virescens (Heliothis pomonella spp.), heliothis virescens (stem borer), heliothis virescens (Sesamia infestans) (pink rice stem borer), heliothis virescens (Sesamia nonagrioides), heliothis virescens (Setora nitens), heliothis virescens (Sitotrogycephalella cerealis) (Angous grandiflora molh), graptopetra virescens (Spannothritis Pillera), heliothis virescens (Spodoptera spp.), spodoptera sp.Spodoptera (Spodoptera spp.), spodoptera exigua (Spodoptera armyworm) (northern armyworm), spodoptera frugiperda (southern armyworm) (southern armyworm (Spodoptera)) The species Spodoptera (Synanthedon spp.) (rootworm), therlla basilides, thermodisia gemmatalis, chlamydia armyworms (tuneola bisselella) (webbing clothes mols), trichoplusia ni (cab looper), dinophora lycopersica (Tuts absoluta), nematopsis species (Yonomeuta spp.), cochloalboth coffee pard (Zezea coreae) (redbranch borer) and Zeuzera pyrina (Leopypoda Drech).
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) (mormondsia longhorns (Mormon cricket)), mole cricket (Gryllotalpidae) (mole cricket), locusta migratoria (Locusta migratoria), grasshopper species (Melanoplus spp) (grasshopper), class wing spurs (Microcentrum retrierve) (angular wing grasshopper), pterophyces spp (pterophyces spp) (pterocarpus stolonifera), steceria gregaria, pterocarpus stolonifera (Scudenria furdata) (pterocarpus stolonicera (fork tailed bukalydid)) and black horny grassland (Vanilla ridge)).
Phthiraptera (Phthiraptera) (sucking lice)): the blood sucking lice species (haematoponus spp.) (cattle and pig lice), sheep jaw lice (linogluchus ovilus) (sheep lice), head lice (pediluus humanus capitis) (body lice), human body lice (pediluus humanus) (body lice) and crab lice (Pthirus pubis) (crab lice louse).
Siphonaptera (daphnaptera) (fleas): ctenocephalides canis (dog flea), ctenocephalides felis (cat flea) and human flea (Pulex irutans) (human flea).
Thysanoptera (thrips): tobacco brown Thrips (Frankliniella fusca) (tobaco third), frankliniella occidentalis (western flower), frankliniella shultzii (Frankliniella occidentalis), frankliniella wilsonii (Frankliniella williamsii) (corn Thrips), frankliniella glasshouse Thrips (IIelothrips haemopralidis) (grenenhouse third), riphithothrips cruentus, scirpus sp (Scrtothrips spp), platycodon grandiflorum (Scrtothricis) (citrus Thrips), tea yellow thistle (Scirnothia) (yellow tea leaf third), taennoththrips and Thrips (Thripp).
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)): <xnotran> 4736 zxft 4736 (Acarapsis woodi) ( (tracheal mite ofhoneybee)), (Acarus spp.) ( ), (Acarus siro) (8978 zxft 8978 (grain mite)), (Aceria mangiferae) (mango bud mite), (Aculops spp.), (Aculops lycopersici) (tomato russet mite), aculops pelekasi, (Aculus pelekassi), (Aculus schlechtendali) ( (apple rust mite)), (Amblyomma amcricanum) (lone star tick), (Boophilus spp.) (), (Brevipalpus obovatus) (privet mite), (Brevipalpus phoenicis) (red and black flat mite), (Demodex spp.) (mange mites), (Dermacentorspp.) ( ), (Dermacentor variabilis) (american dog tick), (Dermatophagoides pteronyssinus) (house dust mite), (Eotetranycus spp.), (Eotetranychus carpini) ( (yellow spider mite)), (Epitimerus spp.), (Eriophyes spp.), (; odes spp.) (), ((Metatetranycus spp.), (Notoedres cati), </xnotran> The species Pediobolus species (Oligonychus spp.), pediobolus coformis (Oligonychus coffee), pediobolus wintergreen (Oligonychus ilicalis (mites), pediobolus species (Panychus spp.), panonychus citri (Panychus citri) (citrus red mite), panonychus ulmi (Panychus ulmi) (European red mite), phyllostachys Purpurens (Phylloptera), rhynchophylla (Chlorococcus flavus) (citrus mite), tarsonemus laterosus (Polygonatum) (Tetranychus urticae (mite)), rhipicephalus rhynchophyllus (Rhipicus sanguineus) (brown mite), tetranychus urticae (Tetranychus urticae) (Tetranychus urticae (mite), tetranychus urticae (Tetranychus urticae), tetranychus urticae (Tetranychus urticae) and Tetranychus urticae (Tetranychus urticae) (Tetranychus urticae (Tetranychus sp).
Nematoda (nematodes): the species Aphelenchoides spp (bud and leaf and pine wood nematodes), the species Trichinella (Belolaimus spp.) (sting nematodes), the species Trichinella (Criconema spp.) (ring nematdes), dirofilaria immitis (dog heartworm), the species Dictylenchus spp.) (stem and bulb nematodes), the species Trichinella (Heterodera spp.) (Cytos nematodes), the species Heterodera (Heterodera cyst) (corn nematodes), the species Meloidogyne spp. (Hirschnella spp.) (Rotenodes) the species neozontalgia (endoplasmius spp.) (surface nematodes), meloidogyne species (Meloidogyne spp.) (root-knot nematodes), meloidogyne incognita (root-knot nematodes), circumflex (oncomelania volvulus) (hook-tail work), praLylenchus (pralylenus spp.) (decay nematodes), perforation (root-knot) species (perforation) and helicobactor (rotilenus reniformis) (kit-shaped-knot nematodes).
General class (general classes of insects): white pine worm (Scutigerella immaculata).
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 10 g to 5 kg of compound per hectare provides adequate control.
The invention also discloses a bactericidal, insecticidal and acaricidal composition which takes the compound shown as 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 between 0.5 and 99 percent. The composition also comprises a carrier acceptable in agriculture, forestry and sanitation.
The compositions of the present invention may be administered in the form of a formulation. The compound shown in the general formula I is used as an active component, dissolved or dispersed in a carrier or prepared into a preparation so as to be easier to disperse when being used for sterilization and disinsection. For example: the chemical preparations can be prepared into wettable powder, oil suspension, water suspension, emulsion in water, aqua, 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 sterilizing, insecticidal and acaricidal composition is applied to the pathogenic bacteria 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.
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 by no means limited to these examples (all materials are commercially available unless otherwise noted).
Synthetic examples
Example 1: synthesis of intermediate 1- (3-chloropyridin-2-yl) piperidin-4-amine hydrochloride
1) Preparation of tert-butyl (1- (5-chloropyridin-2-yl) piperidin-4-yl) carbamate
Figure BDA0002747185910000401
14.8g (0.10 mol) 2,5-dichloropyridine and 16.6g (0.12 mol) potassium carbonate were added to 250mL DMF, and 20.03g (0.10 mol) 4-Boc-aminopiperidine was added thereto, and the temperature was raised to 90 ℃ to react for 3-5 hours. After the completion of the TLC monitoring reaction, the reaction mixture was cooled to room temperature, water was added to precipitate a large amount of solid, which was then filtered, washed with water and dried to give 26.2g of an orange solid with a yield of 84%.
2) Preparation of 1- (5-chloropyridin-2-yl) piperidin-4-amine hydrochloride
Figure BDA0002747185910000402
3.12g (0.01 mol) of tert-butyl (1- (5-chloropyridin-2-yl) piperidin-4-yl) carbamate was added to 50mL of ethyl acetate, 6mL of concentrated hydrochloric acid was added dropwise with stirring at room temperature to dissolve the solid, stirring was continued for 4 to 5 hours, after the completion of the TLC monitoring reaction, the solvent was distilled off under reduced pressure, 10mL of dichloromethane was added with stirring for half an hour, filtration was carried out, and the filter cake was washed with dichloromethane to obtain 2.45g of a yellow solid.
Example 2: synthesis of intermediate 1- (4-nitrophenyl) piperidine-4-amine hydrochloride
1) Preparation of tert-butyl (1- (4-nitrophenyl) piperidin-4-yl) carbamate
Figure BDA0002747185910000403
15.8g (0.10 mol) of 4-Cl nitrobenzene and 16.6g (0.12 mol) of potassium carbonate were added to 250ml of DMF, 20.03g (0.10 mol) of 4-Boc-aminopiperidine was added thereto, and the mixture was heated to 90 ℃ to react for 3 to 5 hours. After the completion of the TLC monitoring reaction, the reaction mixture was cooled to room temperature, water was added to precipitate a large amount of solid, which was then filtered, washed with water and dried to give 25.7g of a yellow solid with a yield of 80%.
2) Preparation of 1- (4-nitrophenyl) piperidin-4-amine hydrochloride
Figure BDA0002747185910000404
3.21g (0.01 mol) of tert-butyl (1- (4-nitrophenyl) piperidin-4-yl) carbamate was added to 50mL of ethyl acetate, 6mL of concentrated hydrochloric acid was added dropwise with stirring at room temperature to dissolve the solid, stirring was continued for 4 to 5 hours, after completion of the reaction monitored by TLC, the solvent was distilled off under reduced pressure, 10mL of methylene chloride was added and stirred for half an hour, and then the mixture was filtered, and the filter cake was washed with methylene chloride to obtain 2.36g of a yellow solid.
Example 3: synthesis of intermediate 1- (5-chloro (6-ethyl) pyrimidine) piperidine-4-amine hydrochloride
1) Preparation of tert-butyl (1- (5-chloro (6-ethyl) pyrimidine) piperidin-4-yl) carbamic acid
Figure BDA0002747185910000405
17.7g (0.10 mol) 4,5-dichloro-6-ethylpyrimidine and 16.6g (0.12 mol) potassium carbonate were added to 250mL DMF, and 20.03g (0.10 mol) 4-Boc-aminopiperidine was added thereto, and the temperature was raised to 90 ℃ to react for 3 to 5 hours. After the completion of the TLC monitoring reaction, the reaction mixture was cooled to room temperature, water was added to precipitate a large amount of solid, which was then filtered, washed with water and dried to obtain 28.7g of a white solid with a yield of 84.4%.
2) Intermediate 1- (5-chloro (6-ethyl) pyrimidine) piperidine-4-amine hydrochloride
Figure BDA0002747185910000411
3.40g (0.01 mol) of tert-butyl (1- (5-chloro (6-ethyl) pyrimidine) piperidin-4-yl) carbamic acid was added to 50mL of ethyl acetate, 6mL of concentrated hydrochloric acid was added dropwise with stirring at room temperature, the solid was dissolved, stirring was continued for 4 to 5 hours, after completion of the TLC monitoring reaction, the solvent was distilled off under reduced pressure, 10mL of dichloromethane was added and stirring was carried out for half an hour, filtration was carried out, and the filter cake was washed with dichloromethane to obtain 2.21g of a white solid.
Example 4: synthesis of intermediate 1- (5-chloropyrimidin-2-yl) piperidin-4-amine hydrochloride
1) Preparation of tert-butyl (1- (5-chloropyrimidin-2-yl) piperidin-4-yl) carbamate
Figure BDA0002747185910000412
14.9g (0.10 mol) 2,5-dichloropyrimidine and 16.6g (0.12 mol) potassium carbonate were added to 250ml DMF, 20.03g (0.10 mol) 4-Boc-aminopiperidine was added, and the temperature was raised to 90 ℃ to react for 3 to 5 hours. After the completion of the TLC monitoring reaction, the reaction mixture was cooled to room temperature, water was added to produce a large amount of solid, which was then filtered, washed with water and dried to give 26.7g of a yellow solid with a yield of 85%.
2) Preparation of 1- (5-chloropyrimidin-2-yl) piperidin-4-amine hydrochloride
Figure BDA0002747185910000413
3.13g (0.01 mol) of tert-butyl (1- (5-chloropyrimidin-2-yl) piperidin-4-yl) carbamate was added to 50mL of ethyl acetate, 6mL of concentrated hydrochloric acid was added dropwise with stirring at room temperature to dissolve the solid, stirring was continued for 4 to 5 hours, after completion of the TLC monitoring reaction, the solvent was distilled off under reduced pressure, 10mL of dichloromethane was added and stirring was continued for half an hour, filtration was carried out, and the filter cake was washed with dichloromethane to obtain 2.16g of a yellow solid.
Example 5: preparation of Compounds 14-18
Figure BDA0002747185910000414
0.25g (1.0 mmol) of 1- (5-chloropyridin-2-yl) piperidin-4-ylamine hydrochloride and 0.17g (1.2 mmol) of potassium carbonate were added to 20mL of DMF, and then 0.18g (1.0 mmol) of 4,5-dichloro-6-ethylpyrimidine was added thereto and heated to 90 ℃ for reaction for 2 to 6 hours. After the completion of the TLC monitoring reaction, the reaction mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, and then dried, filtered, and desolventized under reduced pressure. The residue was purified by column chromatography (eluent ethyl acetate and petroleum ether (boiling range 60-90 ℃ C.), volume ratio 1:4) to give 0.31g of an orange oil in 88.6% yield.
1 H-NMR (600 MHz, internal standard TMS, solvent CDCl 3 )δ(ppm):8.43(s,1H,pyrimidyl-2-H),8.11(d,J ＝2.6Hz,1H,pyridinyl-6-H),7.42(dd,J＝9.0,2.6Hz,1H,pyridinyl-4-H),6.63(d,J＝9.0Hz,1H, pyridinyl-3-H),5.27(d,J＝5.9Hz,1H,NH),4.25-4.33(m,1H,piperidyl-CH),4.23(d,J＝13.6 Hz,2H,piperidyl-2,6-2H),3.05–3.14(m,2H,piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ), 2.15(d,J＝10.1Hz,2H,piperidyl-3,5-2H),1.62–1.76(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6 Hz,3H,CH 2 CH 3 ).
Example 6: preparation of Compounds 46-40
Figure BDA0002747185910000421
0.26g (1.0 mmol) of 1- (4-nitrophenyl) piperidin-4-amine hydrochloride and 0.17g (1.2 mmol) of potassium carbonate were added to 20ml DFF, and then 0.16g (1.0 mmol) of 4,5-dichloro-6-methylpyrimidine was added thereto and heated to 90 ℃ for reaction for 2-6 hours. After the completion of the TLC monitoring reaction, the reaction mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, and then dried, filtered, and desolventized under reduced pressure. The residue was purified by column chromatography (eluent ethyl acetate and petroleum ether (boiling range 60-90 ℃ C.), volume ratio 1:7) to give 0.30g of a yellow solid, 85.7% yield, m.p. 169.8 ℃.
1 H-NMR (600 MHz, internal standard TMS, solvent CDCl 3 )δ(ppm):8.39(s,1H,pyrimidyl-2-H),8.13(d,J ＝9.4Hz,2H,phenyl-3,5-2H),6.85(d,J＝9.4Hz,2H,phenyl-2,6-2H),5.23(d,J＝7.1Hz,1H, NH),4.26–4.35(m,1H,piperidyl-1H),3.98(d,J＝13.3Hz,2H,piperidyl-2,6-2H),3.16–3.22(m, 2H,piperidyl-2,6-2H),2.46(s,3H,CH 3 ),2.19-2.24(m,2H,piperidyl-3,5-2H),1.62(ddd,J＝15.6, 12.4,3.9Hz,2H,piperidyl-3,5-2H)
Example 7: preparation of Compounds 58-69
Figure BDA0002747185910000422
0.28g (1.0 mmol) of 1- (5-chloro (6-ethyl) pyrimidine) piperidin-4-ylamine hydrochloride and 0.17g (1.2 mmol) of potassium carbonate were placed in 20mL of DMF, and then 0.18g (1.0 mmol) of 4,5-dichloro-6-ethylpyrimidine was added and heated to 90 ℃ for reaction for 2 to 6 hours. After the completion of the TLC monitoring reaction, the reaction mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, and then dried, filtered, and desolventized under reduced pressure. The residue was purified by column chromatography (eluent ethyl acetate and petroleum ether (boiling range 60-90 ℃ C.), volume ratio 1:4) to give 0.31g of white solid in 81.6% yield.
1 H NMR(300MHz,CDCl 3 )δ8.5(s,1H,pyrimidyl-2-H),8.43(s,1H,pyrimidyl-2-H),5.30(d, J＝7.5Hz,1H,NH),4.20–4.38(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.11–3.19(m,2H, piperidyl-2,6-2H),2.75-2.91(m,4H,pyrimidinyl-2CH 2 ),2.17-2.21(m,2H,piperidyl-3,5-2H), 1.61-1.73(m,2H,piperidyl-3,5-2H),1.24-1.31(m,6H,pyrimidinyl-2CH 3 ).
Example 8: preparation of Compounds 68-31
Figure BDA0002747185910000423
0.25g (1.0 mmol) of 1- (5-chloropyrimidin-2-yl) piperidin-4-ylamine hydrochloride and 0.17g (1.2 mmol) of potassium carbonate were placed in 20ml of DMF, and then 0.16g (1.0 mmol) of 4,5-dichloro-6-methylpyrimidine was added thereto and heated to 90 ℃ for reaction for 2 to 6 hours. After the completion of the TLC monitoring reaction, the reaction mixture was added to water, extracted with ethyl acetate, and the organic phase was washed with water and saturated brine, respectively, and then dried, filtered, and desolventized under reduced pressure. The residue was purified by column chromatography (eluent ethyl acetate and petroleum ether (boiling range 60-90 ℃ C.), volume ratio 1:5) to give 0.29g of a yellow solid, yield 85.3%, m.p. 185.6 ℃.
1 H NMR(600MHz,CDCl 3 )δ8.39(s,1H,pyrimidyl-2-H),8.13–8.31(m,2H, pyrimidyl-4,6-2H),5.23(s,1H,NH),4.67(d,J＝13.9Hz,2H,piperidyl-2,6-2H),4.30(s,1H, piperidyl-CH),3.15(t,J＝12.7Hz,2H,piperidyl-2,6-2H),2.46(s,3H,CH 3 ),2.14(d,J＝11.7Hz, 2H,piperidyl-3,5-2H),1.63–1.75(m,2H,piperidyl-3,5-2H).
Other compounds of the invention may be prepared by reference to the above examples.
Physical property data and nuclear magnetic data of some of the compounds ( 1 HNMR,600MHz, internal standard TMS, ppm) as follows:
compounds 13-21, oil. Delta (CDCl) 3 ):8.38(s,1H,pyrimidyl-2-H),8.13(d,J＝2.3Hz,1H, pyridinyl-6-H),7.60(d,J＝2.3Hz,1H,pyridinyl-4-H),5.29(d,J＝7.8Hz,1H,NH),4.18–4.28 (m,1H,piperidyl-CH),3.79(d,J＝13.2Hz,2H,piperidyl-2,6-2H),2.99–3.10(m,2H, piperidyl-2,6-2H),2.47(s,3H,CH 3 ),2.17(d,J＝9.3Hz,2H,piperidyl-3,5-2H),1.66–1.78(m,2H, piperidyl-3,5-2H).
Compounds 14-21, oil. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.13(d,J＝2.2Hz,1H, pyridinyl-6-H),7.60(d,J＝2.2Hz,1H,pyridinyl-4-H),5.33(d,J＝7.6Hz,1H,NH),4.19–4.28 (m,1H,piperidyl-CH),3.80(d,J＝13.1Hz,2H,piperidyl-2,6-2H),3.01–3.09(m,2H, piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.18(d,J＝10.0Hz,2H,piperidyl-3,5-2H), 1.67–1.76(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6Hz,3H,CH 2 CH 3 ).
15-21 of the compound, namely oil. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),8.13(t,J＝4.1Hz,1H, pyridinyl-6-H),7.61(d,J＝2.3Hz,1H,pyridinyl-4-H),6.72(t,J＝53.7Hz,1H,CHF 2 ),5.56(d,J ＝7.5Hz,1H,NH),4.23–4.37(m,1H,piperidyl-CH),3.81(d,J＝13.3Hz,2H,piperidyl-2,6-2H), 3.00–3.10(m,2H,piperidyl-2,6-2H),2.13–2.24(m,2H,piperidyl-3,5-2H),1.70–1.78(m,2H, piperidyl-3,5-2H).
Compounds 13-157, oil. Delta (CDCl) 3 ):8.45(s,1H,pyridinyl-6-H),8.41(d,J＝1.0Hz,1H, pyrimidyl-2-H),7.76(d,J＝1.9Hz,1H,pyridinyl-4-H),5.31(d,J＝7.6Hz,1H,NH),4.18–4.38 (m,1H,piperidyl-CH),4.07(d,J＝13.2Hz,2H,piperidyl-2,6-2H),3.08–3.24(m,2H, piperidyl-2,6-2H),2.47(d,J＝1.3Hz,3H,CH 3 ),2.15–2.29(m,2H,piperidyl-3,5-2H),1.68–1.74 (m,2H,piperidyl-3,5-2H).
14-157 melting point 98.4 ℃. Delta (CDCl) 3 ):8.44(s,1H,pyridinyl-6-H),8.40(d,J＝1.0Hz,1H, pyrimidyl-2-H),7.76(d,J＝1.9Hz,1H,pyridinyl-4-H),5.30(d,J＝7.6Hz,1H,NH),4.18–4.38 (m,1H,piperidyl-CH),4.06(d,J＝13.2Hz,2H,piperidyl-2,6-2H),3.06–3.22(m,2H, piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.14–2.26(m,2H,piperidyl-3,5-2H),1.68– 1.74(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6Hz,3H,CH 2 CH 3 ).
15-157 of compound (E), oil. Delta (CDCl) 3 ):8.43(s,1H,pyridinyl-6-H),8.40(d,J＝1.0Hz,1H, pyrimidyl-2-H),7.75(d,J＝1.9Hz,1H,pyridinyl-4-H),6.72(t,J＝53.7Hz,1H,CHF 2 ),5.30(d,J ＝7.6Hz,1H,NH),4.18–4.38(m,1H,piperidyl-CH),4.05(d,J＝13.2Hz,2H,piperidyl-2,6-2H), 3.06–3.21(m,2H,piperidyl-2,6-2H),2.15–2.26(m,2H,piperidyl-3,5-2H),1.64–1.76(m,2H, piperidyl-3,5-2H).
Compound 8-157, mp 157.8 ℃. Delta (CDCl) 3 ):8.38(s,1H,pyrimidyl-2-H),8.17(s,1H, pyridinyl-6-H),7.76(d,J＝1.9Hz,1H,pyridinyl-4-H),5.44(s,1H,NH),4.11–4.22(m,1H, piperidyl-CH),4.00(d,J＝13.3Hz,2H,piperidyl-2,6-2H),3.06(t,J＝13.7Hz,2H, piperidyl-2,6-2H),2.09(d,J＝9.6Hz,2H,piperidyl-3,5-2H),1.60–1.66(m,2H,piperidyl-3,5-2H).
10-157 of compound, oil. Delta (CDCl) 3 ):8.39(s,1H,pyrimidyl-2-H),8.10(s,1H,pyridinyl-6-H), 7.76(d,J＝2.0Hz,1H,pyridinyl-4-H),4.84(d,J＝7.4Hz,1H,NH),4.19–4.38(m,1H, piperidyl-CH),4.06(d,J＝13.2Hz,2H,piperidyl-2,6-2H),3.38(s,2H,NH 2 ),3.09–3.18(m,2H, piperidyl-2,6-2H),2.21(d,J＝10.2Hz,2H,piperidyl-3,5-2H),1.66–1.73(m,2H, piperidyl-3,5-2H).
Compound 14-156, oil. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.01(d,J＝1.0Hz,1H, pyridinyl-6-H),7.44(d,J＝1.9Hz,1H,pyridinyl-4-H),5.34(d,J＝7.7Hz,1H,NH),4.14–4.29 (m,1H,piperidyl-CH),3.72(d,J＝13.0Hz,2H,piperidyl-2,6-2H),2.95–3.10(m,2H, piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.22–2.28(m,3H,CH 3 ),2.13–2.21(m,2H, piperidyl-3,5-2H),1.70–1.76(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6Hz,3H,CH 2 CH 3 ).
46-136 melting point 125.7 ℃. Delta (CDCl) 3 ):8.41(s,1H,pyrimidyl-2-H),7.62(d,J＝1.8Hz, 1H,phenyl-3-H),7.47(dd,J＝8.4,1.7Hz,1H,phenyl-5-H),7.11(d,J＝8.4Hz,1H,phenyl-6-H), 5.41(d,J＝6.8Hz,1H,NH),4.17–4.31(m,1H,piperidyl-CH),3.48(d,J＝12.4Hz,2H, piperidyl-2,6-2H),2.86–3.01(m,2H,piperidyl-2,6-2H),2.21(dd,J＝13.1,2.8Hz,2H, piperidyl-3,5-2H),1.71–1.89(m,2H,piperidyl-3,5-2H).
Compounds 47-136, melting point 115.0 ℃. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),7.62(d,J＝1.5Hz, 1H,phenyl-3-H),7.47(dd,J＝8.4,1.4Hz,1H,phenyl-5-H),7.11(d,J＝8.4Hz,1H,phenyl-6-H), 5.32(d,J＝7.4Hz,1H,NH),4.16–4.27(m,1H,piperidyl-CH),3.47(d,J＝12.3Hz,2H, piperidyl-2,6-2H),2.91(t,J＝10.8Hz,2H,piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ), 2.22(d,J＝12.3Hz,2H,piperidyl-3,5-2H),1.71–1.87(m,piperidyl-3,5-2H),1.28(t,J＝7.6Hz, 3H,CH 2 CH 3 ).
Compounds 48-136 oil. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),7.63(d,J＝1.6Hz,1H, phenyl-3-H),7.48(d,J＝8.4Hz,1H,phenyl-5-H),7.11(d,J＝8.4Hz,1H,phenyl-6-H),6.73(t,J＝ 53.7Hz,1H,CHF 2 ),5.57(d,J＝7.5Hz,1H,NH),4.22–4.39(m,1H,piperidyl-CH),3.49(d,J＝ 12.3Hz,2H,piperidyl-2,6-2H),2.88–3.01(m,2H,piperidyl-2,6-2H),2.23(d,J＝10.4Hz,2H, piperidyl-3,5-2H),1.73–1.90(m,2H,piperidyl-3,5-2H).
58-69 melting point 101.0 ℃. Delta (CDCl) 3 ):8.5(s,1H,pyrimidyl-2-H),8.43(s,1H, pyrimidyl-2-H),5.33(d,J＝7.6Hz,1H,NH),4.16–4.28(m,1H,piperidyl-CH),3.80(d,J＝13.1 Hz,2H,piperidyl-2,6-2H),2.98–3.12(m,2H,piperidyl-2,6-2H),2.80(q,J＝7.6Hz,4H,CH 2 CH 3 ), 2.18(d,J＝10.0Hz,2H,piperidyl-3,5-2H),1.66–1.78(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6 Hz,6H,CH 2 CH 3 ).
15-16 of compound, melting point 99.2 ℃. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),8.19(d,J＝4.6Hz,1H, pyridinyl-6-H),7.60(d,J＝7.7Hz,1H,pyridinyl-4-H),6.84–6.89(m,1H,pyridinyl-5-H),6.73(t, J＝53.7Hz,1H,CHF2),5.58(d,J＝7.4Hz,1H,NH),4.20–4.40(m,1H,piperidyl-CH),3.84(d, J＝12.9Hz,2H,piperidyl-2,6-2H),3.07(t,J＝12.0Hz,2H,piperidyl-2,6-2H),2.20(d,J＝11.7Hz, 2H,piperidyl-3,5-2H),1.72–1.89(m,2H,piperidyl-3,5-2H).
Compounds 13-16, oil. Delta (CDCl) 3 ):8.40(s,1H,pyrimidyl-2-H),8.19(d,J＝4.7Hz,1H, pyridinyl-6-H),7.60(d,J＝7.7Hz,1H,pyridinyl-4-H),6.74–6.93(m,1H,pyridinyl-5-H),5.41(d, J＝7.3Hz,1H,NH),4.20–4.33(m,1H,piperidyl-CH),3.82(d,J＝12.9Hz,2H, piperidyl-2,6-2H),3.06(t,J＝12.1Hz,2H,piperidyl-2,6-2H),2.49(s,3H,CH3),2.18(d,J＝10.9 Hz,2H,piperidyl-3,5-2H),1.67–1.82(m,2H,piperidyl-3,5-2H).
14-16, oil. Delta (CDCl) 3 ):8.49(s,1H,pyrimidyl-2-H),8.19(d,J＝4.4Hz,1H, pyridinyl-6-H),7.60(d,J＝7.6Hz,1H,pyridinyl-4-H),6.81–6.90(m,1H,pyridinyl-5-H),5.64(s, 1H,NH),4.24–4.36(m,1H,piperidyl-CH),3.84(d,J＝12.8Hz,2H,piperidyl-2,6-2H),3.07(t,J ＝12.0Hz,2H,piperidyl-2,6-2H),2.90(dd,J＝14.9,7.4Hz,2H,CH 2 CH 3 ),2.19(d,J＝11.4Hz,2H, piperidyl-3,5-2H),1.72–1.82(m,2H,piperidyl-3,5-2H),1.32(t,J＝7.5Hz,3H,CH 2 CH 3 ).
Compound 15-1, oil. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),8.20(d,J＝3.3Hz,1H, pyridinyl-6-H),7.46–7.52(m,1H,pyridinyl-4-H),6.72(t,J＝52.2Hz,1H,CHF 2 ),6.70(d,J＝8.6 Hz,1H,pyridinyl-5-H),6.63(dd,J＝7.3,4.7Hz,1H,pyridinyl-3-H),5.51(d,J＝7.4Hz,1H,NH), 4.22–4.36(m,1H,piperidyl-CH),4.28–4.32(m,2H,piperidyl-2,6-2H),3.03–3.15(m,2H, piperidyl-2,6-2H),2.16(d,J＝10.2Hz,2H,piperidyl-3,5-2H),1.55–1.67(m,2H, piperidyl-3,5-2H).
15-18 of the compound, oil. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),8.12(d,J＝2.6Hz,1H, pyridinyl-6-H),7.43(dd,J＝9.0,2.6Hz,1H,pyridinyl-4-H),6.72(t,J＝52.2Hz,1H,CHF 2 ),6.64 (d,J＝9.1Hz,1H,pyridinyl-3-H),5.50(d,J＝7.3Hz,1H,NH),4.26–4.38(m,1H,piperidyl-CH), 4.25(d,J＝13.5Hz,2H,piperidyl-2,6-2H),2.95–3.19(m,2H,piperidyl-2,6-2H),2.07–2.26(m, 2H,piperidyl-3,5-2H),1.60–1.66(m,2H,piperidyl-3,5-2H).
13-18, oil. Delta (CDCl) 3 ):8.39(s,1H,pyrimidyl-2-H),8.12(d,J＝2.6Hz,1H, pyridinyl-6-H),7.42(dd,J＝9.0,2.6Hz,1H,pyridinyl-4-H),6.62–6.67(m,1H,pyridinyl-3-H), 5.30(s,1H,NH),4.26–4.33(m,1H,piperidyl-CH),4.24(d,J＝13.9Hz,2H,piperidyl-2,6-2H), 3.01–3.18(m,2H,piperidyl-2,6-2H),2.48(s,3H,CH 3 ),2.14(d,J＝12.8Hz,2H, piperidyl-3,5-2H),1.67–1.76(m,2H,piperidyl-3,5-2H).
Compound 14-57, oil. Delta (CDCl) 3 ):8.42(s,1H,pyrimidyl-2-H),8.03(s,1H,pyridinyl-6-H), 7.32(d,J＝8.3Hz,1H,pyridinyl-4-H),6.64(d,J＝8.4Hz,1H,pyridinyl-3-H),5.26(d,J＝6.5Hz, 1H,NH),4.18–4.28(m,1H,piperidyl-CH),4.20(d,J＝12.8Hz,2H,piperidyl-2,6-2H),3.72(q,J ＝6.8Hz,2H,piperidyl-2,6-2H),3.06(t,J＝12.2Hz,2H,piperidyl-3,5-2H),2.79(q,J＝7.3Hz,2H, CH 2 CH 3 ),2.20(s,3H,CH 3 ),2.14(d,J＝12.4Hz,2H,piperidyl-3,5-2H),1.25(t,J＝7.5Hz,3H, CH 2 CH 3 ).
15-47 melting point 165 ℃. Delta (CDCl) 3 ):8.57(s,1H,pyrimidyl-2-H),8.29(d,J＝4.5Hz,1H, pyridinyl-6-H),6.86(s,1H,pyridinyl-3-H),6.77(d,J＝4.5Hz,1H,pyridinyl-5-H),6.72(t,J＝ 53.4Hz,1H,CHF 2 ),5.49(d,J＝6.8Hz,1H,NH),4.34(d,J＝13.3Hz,3H,piperidyl-2,6-2H, piperidyl-CH),3.15(t,J＝12.6Hz,2H,piperidyl-2,6-2H),2.20(d,J＝12.5Hz,2H, piperidyl-3,5-2H),1.52–1.62(m,2H,piperidyl-3,5-2H).
Compound 14-153 oil. Delta (CDCl) 3 ):8.40(s,1H,pyrimidyl-2-H),8.33(d,J＝2.1Hz,1H, pyridinyl-6-H),7.74(d,J＝21.4Hz,1H,pyridinyl-4-H),7.32(d,J＝8.1Hz,1H,pyridinyl-3-H), 5.27(d,J＝7.3Hz,1H,NH),4.06(s,1H,piperidyl-CH),3.58(s,2H,CH 2 Cl),2.89(s,2H, piperidyl-2,6-2H),2.78(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.25–2.37(m,2H,piperidyl-2,6-2H),2.08(d, J＝11.8Hz,2H,piperidyl-3,5-2H),1.58–1.76(m,2H,piperidyl-3,5-2H),1.26(t,J＝7.6Hz,3H, CH 2 CH 3 ).
Compounds 14-48, oil. Delta (CDCl) 3 ):8.43(s,1H,pyridinyl-6-H),8.42(d,J＝2.1Hz,1H, pyrimidyl-2-H),7.62(dd,J＝9.0,2.2Hz,1H,pyridinyl-4-H),6.65(d,J＝9.0Hz,1H, pyridinyl-3-H),5.23(d,J＝7.6Hz,1H,NH),4.43(d,J＝13.6Hz,2H,piperidyl-2,6-2H),4.29– 4.37(m,1H,piperidyl-CH),3.14–3.24(m,2H,piperidyl-2,6-2H),2.79(q,J＝7.6Hz,2H, CH 2 CH 3 ),2.20(d,J＝9.6Hz,2H,piperidyl-3,5-2H),1.43–1.64(m,2H,piperidyl-3,5-2H),1.27(t, J＝7.5Hz,3H,CH 2 CH 3 ).
15-48 of compound, melting point 202.5 ℃. Delta (CDCl) 3 ):8.56(s,1H,pyridinyl-6-H),8.42(d,J＝1.9Hz,1H, pyrimidyl-2-H),7.57–7.68(m,1H,pyridinyl-4-H),6.72(t,J＝53.4Hz,1H,CHF 2 ),6.66(d,J＝ 9.0Hz,1H,pyridinyl-3-H),5.49(d,J＝7.2Hz,1H,NH),4.46(d,J＝13.6Hz,2H, piperidyl-2,6-2H),4.33–4.42(m,1H,piperidyl-CH),3.14–3.23(m,2H,piperidyl-2,6-2H),2.21 (d,J＝10.6Hz,2H,piperidyl-3,5-2H),1.50–1.61(m,2H,piperidyl-3,5-2H).
Compound 14-31, melting point 112.1 ℃. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.23(d,J＝4.6Hz, 1H,pyridinyl-6-H),7.79(d,J＝7.7Hz,1H,pyridinyl-4-H),6.70–6.83(m,1H,pyridinyl-5-H), 5.34(d,J＝7.5Hz,1H,NH),4.18–4.28(m,1H,piperidyl-CH),3.78(d,J＝12.7Hz,2H, piperidyl-2,6-2H),3.05(t,J＝11.9Hz,2H,piperidyl-2,6-2H),2.80(q,J＝7.5Hz,2H,CH 2 CH 3 ), 2.20(t,J＝13.1Hz,2H,piperidyl-3,5-2H),1.70–1.80(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6 Hz,3H,CH 2 CH 3 ).
Compound 14-2, melting point 95.8 ℃. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.01(d,J＝4.2Hz,1H, pyridinyl-6-H),7.23(dd,J＝12.8,7.9Hz,1H,pyridinyl-4-H),6.75(s,1H,pyridinyl-5-H),5.31(d, J＝7.2Hz,1H,NH),4.20–4.32(m,1H,piperidyl-CH),4.06(d,J＝13.1Hz,2H, piperidyl-2,6-2H),3.12(t,J＝12.3Hz,2H,piperidyl-2,6-2H),2.79(q,J＝7.5Hz,2H,CH 2 CH 3 ), 2.17(d,J＝12.1Hz,2H,piperidyl-3,5-2H),1.61–1.73(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.5 Hz,3H,CH 2 CH 3 ).
Compound 48-40 oil delta (CDCl) 3 ):8.57(s,1H,pyrimidyl-2-H),8.14(d,J＝9.4Hz,2H, phenyl-3,5-2H),6.86(d,J＝9.4Hz,2H,phenyl-2,6-2H),6.72(t,J＝53.7Hz,1H,CHF 2 ),5.50(d,J ＝7.2Hz,1H,NH),4.33–4.42(m,1H,piperidyl-CH),3.99(d,J＝13.1Hz,2H,piperidyl-2,6-2H), 3.19(t,J＝11.5Hz,2H,piperidyl-2,6-2H),2.23(d,J＝9.7Hz,2H,piperidyl-3,5-2H),1.62–1.70 (m,2H,piperidyl-3,5-2H).
Compound 47-40, melting point 156 ℃. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.12(d,J＝9.3Hz,2H, phenyl-3,5-2H),6.85(d,J＝9.3Hz,2H,phenyl-2,6-2H),5.28(d,J＝7.5Hz,1H,NH),4.22–4.41 (m,1H,piperidyl-CH),3.98(d,J＝13.4Hz,2H,piperidyl-2,6-2H),3.15–3.28(m,2H, piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.20(t,J＝15.4Hz,2H,piperidyl-3,5-2H), 1.58–1.68(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.5Hz,3H,CH 2 CH 3 ).
Compounds 47-161 oil. Delta (CDCl) 3 ):8.41(s,1H,pyrimidyl-2-H),7.36(t,J＝8.2Hz,1H, phenyl-5-H),7.20–7.24(m,1H,phenyl-4-H),7.16–7.20(m,1H,phenyl-6-H),5.26(d,J＝7.7Hz, 1H,NH),4.05–4.21(m,1H,piperidyl-CH),3.25(d,J＝12.2Hz,2H,piperidyl-2,6-2H),2.87– 2.97(m,2H,piperidyl-2,6-2H),2.79(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.13(d,J＝11.1Hz,2H, piperidyl-3,5-2H),1.61–1.71(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6Hz,3H,CH 2 CH 3 ).
48-161 of compound, melting point 221.3 ℃. Delta (CDCl) 3 ):8.54(s,1H,pyrimidyl-2-H),7.37(t,J＝8.2Hz, 1H,phenyl-5-H),7.24(dd,J＝8.1,1.0Hz,1H,phenyl-4-H),7.19(dd,J＝8.2,0.9Hz,1H, phenyl-6-H),6.72(t,J＝53.7Hz,1H,CHF 2 ),5.51(d,J＝7.6Hz,1H,NH),4.15–4.26(m,1H, piperidyl-CH),3.26(d,J＝12.4Hz,2H,piperidyl-2,6-2H),2.89–3.03(m,2H,piperidyl-2,6-2H), 2.14(d,J＝10.8Hz,2H,piperidyl-3,5-2H),1.63–1.75(m,piperidyl-3,5-2H).
Compound 46-161 oil. Delta (CDCl) 3 ):8.36(s,1H,pyrimidyl-2-H),7.36(t,J＝8.2Hz,1H, phenyl-5-H),7.22(d,J＝8.1Hz,1H,phenyl-4-H),7.18(d,J＝8.2Hz,1H,phenyl-6-H),5.25(d,J ＝7.7Hz,1H,NH),4.10–4.18(m,1H,piperidyl-CH),3.25(d,J＝12.3Hz,2H,piperidyl-2,6-2H), 2.80–3.02(m,2H,piperidyl-2,6-2H),2.46(s,3H,CH 3 ),2.13(d,J＝11.2Hz,2H, piperidyl-3,5-2H),1.61–1.71(m,2H,piperidyl-3,5-2H).
Compounds 47-163, oil. Delta (CDCl) 3 ):8.42(s,1H,pyrimidyl-2-H),7.76(d,J＝8.3Hz,1H, phenyl-3-H),6.93(s,1H,phenyl-6-H),6.84(d,J＝8.3Hz,1H,phenyl-4-H),5.31(d,J＝8.0Hz, 1H,NH),4.11–4.27(m,1H,piperidyl-CH),3.31(d,J＝12.6Hz,2H,piperidyl-2,6-2H),2.93– 3.09(m,2H,piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.39(s,3H,CH 3 ),2.16(d,J＝ 10.9Hz,2H,piperidyl-3,5-2H),1.71–1.83(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6Hz,3H, CH 2 CH 3 ).
Compounds 48-163, oil. Delta (CDCl) 3 ):8.55(s,1H,pyrimidyl-2-H),7.77(d,J＝8.3Hz,1H, phenyl-3-H),6.95(s,1H,phenyl-6-H),6.84–6.88(m,1H,phenyl-4-H),6.73(t,J＝53.7Hz,1H, CHF 2 ),5.58(d,J＝7.6Hz,1H,NH),4.17–4.38(m,1H,piperidyl-CH),3.33(d,J＝12.6Hz,2H, piperidyl-2,6-2H),2.94–3.04(m,2H,piperidyl-2,6-2H),2.39(s,3H,CH 3 ),2.18(dd,J＝9.1,3.3 Hz,2H,piperidyl-3,5-2H),1.76–1.86(m,piperidyl-3,5-2H).
Compounds 46-163, oil. Delta (CDCl) 3 ):8.38(s,1H,pyrimidyl-2-H),7.76(d,J＝8.3Hz,1H, phenyl-3-H),6.93(s,1H,phenyl-6-H),6.84(d,J＝8.3Hz,1H,phenyl-5-H),5.30(d,J＝7.6Hz, 1H,NH),4.10–4.26(m,1H,piperidyl-CH),3.31(d,J＝12.7Hz,2H,piperidyl-2,6-2H),2.94– 3.04(m,2H,piperidyl-2,6-2H),2.16(d,J＝9.6Hz,2H,piperidyl-3,5-2H),1.71–1.83(m,2H, piperidyl-3,5-2H).
Compounds 47-44 melting Point 185 ℃. Delta (CDCl) 3 ):8.72(d,J＝2.7Hz,1H,phenyl-3-H),8.43(s,1H, pyrimidyl-2-H),8.27(dd,J＝9.3,2.7Hz,1H,phenyl-5-H),7.14(d,J＝9.3Hz,1H,phenyl-6-H), 5.29(d,J＝7.5Hz,1H,NH),4.26–4.32(m,1H,piperidyl-CH),3.51(d,J＝13.3Hz,2H, piperidyl-2,6-2H),3.21–3.31(m,2H,piperidyl-2,6-2H),2.81(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.20– 2.26(m,2H,piperidyl-3,5-2H),1.74–1.78(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6Hz,3H, CH 2 CH 3 ).
48-44 melting point 163.6 ℃ for the compounds. Delta (CDCl) 3 ):8.73(d,J＝2.7Hz,1H,phenyl-3-H),8.56(s,1H, pyrimidyl-2-H),8.29(dd,J＝9.3,2.7Hz,1H,phenyl-5-H),7.15(d,J＝9.3Hz,1H,phenyl-6-H), 6.73(dd,J＝56.3,51.0Hz,1H,CHF 2 ),5.55(d,J＝7.4Hz,1H,NH),4.30–4.40(m,1H, piperidyl-CH),3.52(d,J＝13.4Hz,2H,piperidyl-2,6-2H),3.18–3.35(m,2H,piperidyl-2,6-2H), 2.24(d,J＝9.9Hz,2H,piperidyl-3,5-2H),1.75–1.85(m,2H,piperidyl-3,5-2H).
46-44 for compound, melting point 190 ℃. Delta (CDCl) 3 ):8.72(s,1H,phenyl-3-H),8.38(s,1H,pyrimidyl-2-H), 8.27(d,J＝9.3Hz,1H,phenyl-5-H),7.14(d,J＝9.1Hz,1H,phenyl-6-H),5.27(d,J＝7.0Hz,1H, NH),4.31(t,J＝6.1Hz,1H,piperidyl-CH),3.50(d,J＝13.3Hz,2H,piperidyl-2,6-2H),3.25(t,J＝ 12.7Hz,2H,piperidyl-2,6-2H),2.48(d,J＝1.3Hz,3H,CH 3 ),2.22(d,J＝9.8Hz,2H, piperidyl-3,5-2H),1.68–1.80(m,2H,piperidyl-3,5-2H).
Compounds 69-31, melting Point 111.3 ℃. Delta (CDCl) 3 ):8.44(s,1H,pyrimidyl-2-H),8.23(s,2H, pyrimidyl-4,6-2H),5.25(s,1H,NH),4.67(d,J＝12.8Hz,2H,piperidyl-2,6-2H),4.31(s,1H, piperidyl-CH),3.16(t,J＝12.4Hz,2H,piperidyl-2,6-2H),2.80(q,J＝7.5Hz,2H,CH 2 CH 3 ),2.15 (d,J＝11.7Hz,2H,piperidyl-3,5-2H),1.60–1.70(m,2H,piperidyl-3,5-2H),1.31(t,J＝7.5Hz, 3H,CH 2 CH 3 ).
Compound 14-2, melting point 95.8 ℃. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.01(d,J＝4.2Hz,1H, pyridinyl-6-H),7.23(dd,J＝12.8,7.9Hz,1H,pyridinyl-4-H),6.75(s,1H,pyridinyl-5-H),5.31(d, J＝7.2Hz,1H,NH),4.26(d,J＝7.2Hz,1H,piperidyl-CH),4.06(d,J＝13.1Hz,2H, piperidyl-2,6-2H),3.12(t,J＝12.3Hz,2H,piperidyl-2,6-2H),2.79(q,J＝7.5Hz,2H,CH 2 CH 3 ), 2.17(d,J＝12.1Hz,2H,piperidyl-3,5-2H),1.62–1.72(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.5 Hz,3H,CH 2 CH 3 ).
Compound 14-31, melting point 112.1 ℃. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.23(d,J＝4.6Hz,1H, pyridinyl-6-H),7.79(d,J＝7.7Hz,1H,pyridinyl-4-H),6.70–6.83(m,1H,pyridinyl-5-H),5.34(d, J＝7.5Hz,1H,NH),4.18–4.30(m,1H,piperidyl-CH),3.78(d,J＝12.7Hz,2H, piperidyl-2,6-2H),3.00–3.10(m,2H,piperidyl-2,6-2H),2.80(q,J＝7.5Hz,2H,CH 2 CH 3 ),2.20(d, J＝10.1Hz,2H,piperidyl-3,5-2H),1.71-1.79(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6Hz,3H, CH 2 CH 3 ).
13-50 of compound, melting point 129.8 ℃. Delta (CDCl) 3 ):8.38(s,1H,pyrimidyl-2-H),8.34(d,J＝4.4Hz,1H, pyridinyl-6-H),8.15(d,J＝8.0Hz,1H,pyridinyl-4-H),6.77(dd,J＝7.9,4.5Hz,1H, pyridinyl-5-H),5.28(d,J＝7.5Hz,1H,NH),4.17–4.41(m,1H,piperidyl-CH),3.86(d,J＝13.5 Hz,2H,piperidyl-2,6-2H),3.16–3.26(m,2H,piperidyl-2,6-2H),2.47(s,3H,CH 3 ),2.17(d,J＝ 10.2Hz,2H,piperidyl-3,5-2H),1.65–1.75(m,2H,piperidyl-3,5-2H).
14-50 of compound, oil. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.34(d,J＝4.4Hz,1H, pyridinyl-6-H),8.15(d,J＝8.0Hz,1H,pyridinyl-4-H),6.77(dd,J＝8.0,4.5Hz,1H, pyridinyl-5-H),5.30(d,J＝7.5Hz,1H,NH),4.23–4.42(m,1H,piperidyl-CH),3.86(d,J＝13.5 Hz,2H,piperidyl-2,6-2H),3.21(t,J＝11.9Hz,2H,piperidyl-2,6-2H),2.79(q,J＝7.6Hz,2H, CH 2 CH 3 ),2.19(d,J＝10.3Hz,2H,piperidyl-3,5-2H),1.65–1.72(m,2H,piperidyl-3,5-2H),1.27 (t,J＝7.5Hz,3H,CH 2 CH 3 ).
15-50 of compound, melting point 159.1 ℃. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),8.33–8.40(m,1H, pyridinyl-6-H),8.16(dd,J＝8.0,1.7Hz,1H,pyridinyl-4-H),6.78–6.80(m,1H,pyridinyl-5-H), 6.72(t,J＝53.64Hz,1H,CHF 2 ),5.55(d,J＝7.4Hz,1H,NH),4.24–4.55(m,1H,piperidyl-CH), 3.88(d,J＝13.7Hz,2H,piperidyl-2,6-2H),3.15–3.29(m,2H,piperidyl-2,6-2H),2.12–2.29(m, 2H,piperidyl-3,5-2H),1.65–1.75(m,2H,piperidyl-3,5-2H).
14-17 melting point 99.1 deg.C. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),8.02(d,J＝6.1Hz,1H, pyridinyl-6-H),6.68(d,J＝2.3Hz,1H,pyridinyl-3-H),6.60(dd,J＝6.1,2.4Hz,1H, pyridinyl-5-H),5.28(d,J＝7.4Hz,1H,NH),4.26–4.43(m,1H,piperidyl-CH),3.88(d,J＝13.5 Hz,2H,piperidyl-2,6-2H),3.05–3.19(m,2H,piperidyl-2,6-2H),2.80(q,J＝7.6Hz,2H,CH 2 CH 3 ), 2.18(d,J＝8.9Hz,2H,piperidyl-3,5-2H),1.55–1.61(m,2H,piperidyl-3,5-2H),1.27(t,J＝7.6 Hz,3H,CH 2 CH 3 ).
15-17, oil. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),8.04(t,J＝14.2Hz,1H, pyridinyl-6-H),6.72(t,J＝53.7Hz,1H,CHF 2 ),6.69(d,J＝2.3Hz,1H,pyridinyl-3-H),6.61(dd,J ＝6.1,2.4Hz,1H,pyridinyl-5-H),5.54(d,J＝7.4Hz,1H,NH),4.20–4.54(m,1H,piperidyl-CH), 3.90(d,J＝13.5Hz,2H,piperidyl-2,6-2H),3.04–3.21(m,2H,piperidyl-2,6-2H),2.20(d,J＝9.8 Hz,2H,piperidyl-3,5-2H),1.58–1.65(m,2H,piperidyl-3,5-2H).
14-19 melting point 182.7 ℃. Delta (CDCl) 3 ):8.43(s,1H,pyrimidyl-2-H),7.36–7.44(m,1H, pyridinyl-4-H),6.59(d,J＝7.5Hz,1H,pyridinyl-3-H),6.53(d,J＝8.4Hz,1H,pyridinyl-5-H), 5.27(d,J＝7.6Hz,1H,NH),4.27–4.31(m,1H,piperidyl-CH),4.23–4.28(m,2H, piperidyl-2,6-2H),3.02–3.17(m,2H,piperidyl-2,6-2H),2.79(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.11– 2.20(m,2H,piperidyl-3,5-2H),1.50–1.60(m,2H,piperidyl-3,5-2H),1.26(t,J＝7.6Hz,3H, CH 2 CH 3 ).
15-19 of compound, melting point 110.1 ℃. Delta (CDCl) 3 ):8.56(s,1H,pyrimidyl-2-H),7.40(t,J＝7.9Hz,1H, pyridinyl-4-H),6.72(t,J＝53.7Hz,1H,CHF 2 ),6.61(d,J＝7.5Hz,1H,pyridinyl-3-H),6.54(d,J ＝8.4Hz,1H,pyridinyl-5-H),5.51(d,J＝7.3Hz,1H,NH),4.32–4.37(m,1H,piperidyl-CH),4.30 (d,J＝13.3Hz,2H,piperidyl-2,6-2H),3.01–3.22(m,2H,piperidyl-2,6-2H),2.10–2.23(m,2H, piperidyl-3,5-2H),1.55-1.62(m,2H,piperidyl-3,5-2H).
14-106 of the compound, and the melting point is 94.9 ℃. (CDCl) 3 ):8.41(s,1H,pyrimidyl-2-H),8.27(dd,J＝4.7,2.0Hz, 1H,pyridinyl-6-H),7.99(dd,J＝7.6,2.0Hz,1H,pyridinyl-4-H),6.74(dd,J＝7.6,4.7Hz,1H, pyridinyl-5-H),5.29(d,J＝7.6Hz,1H,NH),4.15–4.34(m,1H,piperidyl-CH),3.88(s,3H, COOCH 3 ),3.81–3.87(m,2H,piperidyl-2,6-2H),3.08–3.19(m,2H,piperidyl-2,6-2H),2.78(q,J ＝7.6Hz,2H,CH 2 CH 3 ),2.08–2.17(m,2H,piperidyl-3,5-2H),1.62–1.72(m,2H, piperidyl-3,5-2H),1.25(t,J＝7.6Hz,3H,CH 2 CH 3 ).
Compounds 13-106, oil. (CDCl) 3 ):8.36(s,1H,pyrimidyl-2-H),8.27(dd,J＝4.7,2.0Hz,1H, pyridinyl-6-H),7.98(dd,J＝7.6,2.0Hz,1H,pyridinyl-4-H),6.73(dd,J＝7.6,4.7Hz,,1H, pyridinyl-5-H),5.27(d,J＝7.8Hz,,1H,NH),4.13–4.39(m,1H,piperidyl-CH),3.88(s,3H, COOCH 3 ),3.81–3.87(m,2H,piperidyl-2,6-2H),3.06–3.18(m,2H,piperidyl-2,6-2H),2.44(s, 1H,CH 3 ),2.06–2.17(m,2H,piperidyl-3,5-2H),1.60–1.75(m,2H,piperidyl-3,5-2H).
15-106 of compound, the melting point is 125.8 ℃. Delta (CDCl) 3 ):8.53(s,1H,pyrimidyl-2-H),8.27(dd,J＝4.7,2.0 Hz,1H,pyridinyl-6-H)),7.99(dd,J＝7.6,2.0Hz,1H,pyridinyl-4-H),6.75(dd,J＝7.6,4.7Hz,1H, pyridinyl-5-H),6.70(t,J＝53.7Hz,1H,CHF 2 ),5.54(d,J＝7.7Hz,1H,NH),4.16–4.45(m,1H, piperidyl-CH),3.88(s,3H,COOCH 3 ),3.80–3.87(m,2H,piperidyl-2,6-2H),3.07–3.16(m,2H, piperidyl-2,6-2H),2.09–2.16(m,2H,piperidyl-3,5-2H),1.63–1.74(m,2H,piperidyl-3,5-2H).
Compound 13-1 melting Point 167.2 ℃. Delta (CDCl) 3 ):8.76–8.92(m,1H,pyridinyl-6-H),8.37(s,1H, pyrimidyl-2-H),8.01(dd,J＝9.0,2.4Hz,1H,pyridinyl-4-H),6.57–6.74(m,1H,pyridinyl-3-H), 5.22(d,J＝7.7Hz,1H,NH),4.44(d,J＝13.6Hz,2H,piperidyl-2,6-2H),4.26–4.35(m,1H, piperidyl-CH),3.86(s,3H,COOCH 3 ),3.11–3.25(m,2H,piperidyl-2,6-2H),2.45(s,3H,CH 3 ), 2.13–2.20(m,2H,piperidyl-3,5-2H),1.47–1.57(m,2H,piperidyl-3,5-2H).
Compound 14-1, melting point 112.7 ℃. Delta (CDCl) 3 ):8.77(d,J＝2.4Hz,1H,pyridinyl-6-H),8.41(s,1H, pyrimidyl-2-H),7.99(dd,J＝9.0,2.4Hz,1H,pyridinyl-4-H),6.61(d,J＝9.1Hz,1H, pyridinyl-3-H),5.23(d,J＝7.7Hz,1H,NH),4.43(d,J＝13.6Hz,2H,piperidyl-2,6-2H),4.23– 4.34(m,1H,piperidyl-CH),3.84(s,3H,COOCH 3 )3.09–3.24(m,2H,piperidyl-2,6-2H),2.76(q, J＝7.6Hz,2H,CH 2 CH 3 ),2.06–2.23(m,2H,piperidyl-3,5-2H),1.45–1.58(m,2H, piperidyl-3,5-2H),1.24(t,J＝7.6Hz,3H,CH 2 CH 3 ).
Compound 15-1, melting point 168.5 ℃. Delta CDCl 3 ):8.79(dd,J＝2.4,0.5Hz,1H,pyridinyl-6-H),8.55(s, 1H,pyrimidyl-2-H),8.02(dd,J＝9.0,2.4Hz,1H,pyridinyl-4-H),6.70(t,J＝53.6Hz,1H,CHF 2 ), 6.64(d,J＝9.1Hz,1H,pyridinyl-3-H),5.48(d,J＝7.6Hz,1H,NH),4.47(d,J＝13.6Hz,2H, piperidyl-2,6-2H),4.31–4.41(m,1H,piperidyl-CH),3.86(s,3H,COOCH 3 ),3.12–3.23(m,2H, piperidyl-2,6-2H),2.13–2.25(m,2H,piperidyl-3,5-2H),1.53–1.57(m,2H,piperidyl-3,5-2H).
Compound 14-1-157, oil. Delta (CDCl) 3 ):8.37(s,1H,pyridinyl-6-H),8.31(d,J＝1.5Hz,1H, pyrimidyl-2-H),7.74(d,J＝1.9Hz,1H,pyridinyl-4-H),4.85(d,J＝6.8Hz,1H,NH),4.20–4.39 (m,1H,piperidyl-CH),4.05(d,J＝13.3Hz,2H,piperidyl-2,6-2H),3.08–3.15(m,2H, piperidyl-2,6-2H),2.70(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.16–2.22(m,2H,piperidyl-3,5-2H),1.64– 1.72(m,2H,piperidyl-3,5-2H),1.26(t,J＝7.6Hz,3H,CH 2 CH 3 ).
Compounds 14-1-16, oil. Delta (CDCl) 3 ):8.31(s,1H,pyrimidyl-2-H),8.17(dd,J＝4.7,1.8Hz, 1H,pyridinyl-6-H),7.58(dd,J＝7.7,1.4Hz,1H,pyridinyl-4-H),6.83(dd,J＝7.8,4.7Hz, pyridinyl-5-H),4.86–4.93(m,J＝6.9Hz,1H,NH),4.17-4.26(m,1H,piperidyl-CH),3.81(d,J＝ 13.1Hz,2H,piperidyl-2,6-2H),3.00–3.08(m,2H,piperidyl-2,6-2H),2.70(q,J＝7.6Hz,2H, CH 2 CH 3 ),2.14–2.22(m,2H,piperidyl-3,5-2H),1.66–1.76(m,2H,piperidyl-3,5-2H),1.26(t,J＝ 7.5Hz,3H,CH 2 CH 3 ).
Compound 14-1-21, melting point 162.5 ℃. Delta (CDCl) 3 ):8.31(s,1H,pyrimidyl-2-H),8.11(d,J＝2.1Hz, 1H,pyridinyl-6-H),7.59(d,J＝2.6Hz,1H,pyridinyl-4-H),4.83–4.90(m,1H,NH),4.15–4.24(m, 1H,piperidyl-CH),3.79(d,J＝13.2Hz,2H,piperidyl-2,6-2H),2.99–3.05(m,2H, piperidyl-2,6-2H),2.70(q,J＝7.6,2H,CH 2 CH 3 ),2.14-2.19(m,2H,piperidyl-3,5-2H),1.64–1.73 (m,2H,piperidyl-3,5-2H),1.26(t,J＝7.6Hz,3H,CH 2 CH 3 ).
58-25 melting point 143.7 ℃. Delta (CDCl) 3 ):8.41(s,1H,pyrimidyl-2-H),8.37(s,1H, pyrimidyl-2-H),6.53(s,1H,pyrimidyl-5-H),5.22(d,J＝7.5Hz,1H,NH),4.24–4.41(m,3H, piperidyl-CH+piperidyl-2,6-2H),3.10–3.19(m,2H,piperidyl-2,6-2H),2.78(q,J＝7.6Hz,2H, CH 2 CH 3 ),2.14–2.21(m,2H,piperidyl-3,5-2H),1.45–1.54(m,2H,piperidyl-3,5-2H),1.25(t,J＝ 7.6Hz,3H,CH 2 CH 3 ).
57-25 melting Point 152.9 ℃. Delta (CDCl) 3 ):8.37(s,2H,pyrimidyl-2-H),6.53(s,1H, pyrimidyl-5-H),5.21(d,J＝7.5Hz,1H,NH),4.19–4.46(m,3H,piperidyl-CH+piperidyl-2,6-2H), 3.08–3.28(m,2H,piperidyl-2,6-2H),2.45(s,3H,CCH 3 ),2.10–2.24(m,2H,piperidyl-3,5-2H), 1.42–1.59(m,2H,piperidyl-3,5-2H).
Compound 58-1-25, melting point 189.8 ℃. Delta (CDCl) 3 ):8.38(d,J＝16.5Hz,1H,pyrimidyl-2-H),8.30(d, J＝1.7Hz,1H,pyrimidyl-2-H),6.53(s,1H,pyrimidyl-5-H),4.83(d,J＝6.7Hz,1H,NH),4.24– 4.46(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.10–3.18(m,2H,piperidyl-2,6-2H),2.70(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.16–2.22(m,2H,piperidyl-3,5-2H),1.45–1.51(m,2H,piperidyl-3,5-2H), 1.25(t,J＝7.6Hz,3H,CH 2 CH 3 ).
Compound 59-25 melting point 195.9 ℃. Delta (CDCl) 3 ):8.55(s,1H,pyrimidyl-2-H),8.38(s,1H, pyrimidyl-2-H),6.70(t,J＝53.7Hz,1H,CHF 2 ),6.54(s,1H,pyrimidyl-5-H),5.48(d,J＝7.4Hz, 1H,NH),4.28–4.51(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.09–3.18(m,2H, piperidyl-2,6-2H),2.15–2.25(m,2H,piperidyl-3,5-2H),1.50–1.60(m,2H,piperidyl-3,5-2H).
Compounds 25-16, melting point 103.1 ℃. Delta (CDCl) 3 ):8.46(s,1H,pyrimidyl-2-H),8.06(d,J＝4.4Hz,1H, pyridinyl-6-H),7.36(d,J＝7.8Hz,1H,pyridinyl-4-H),7.21(dd,J＝7.7,4.7Hz,1H, pyridinyl-5-H),5.54(d,J＝7.5Hz,1H,NH),4.15-4.30(d,J＝7.0Hz,1H,piperidyl-CH),3.45(d, J＝11.6Hz,2H,piperidyl-2,6-2H),2.86(t,J＝12.0Hz,2H,piperidyl-2,6-2H),2.84(q,J＝7.4Hz, 2H,CH 2 CH 3 ),2.21(d,J＝11.0Hz,2H,piperidyl-3,5-2H),1.80–1.87(m,2H,piperidyl-3,5-2H), 1.25(t,J＝7.5Hz,3H,CH 2 CH 3 ).
Compound 80-4 melting point 110.0 deg.C. Delta (CDCl) 3 ):8.41(s,1H,pyrimidyl-2-H),7.20(d,J＝9.6Hz,1H, pyridazinyl-4-H),6.93(d,J＝9.6Hz,1H,pyridazinyl-6-H),5.24(d,J＝7.5Hz,1H,NH),4.25– 4.37(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.14–3.23(m,2H,piperidyl-2,6-2H),2.78(q,J＝ 7.6Hz,2H,CH 2 CH 3 ),2.14–2.21(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H), 1.25(t,J＝7.6Hz,3H,CH 2 CH 3 ).
Compound 79-4, oil. Delta (CDCl) 3 ):8.37(s,1H,pyrimidyl-2-H),7.20(d,J＝9.6Hz,1H, pyridazinyl-4-H),6.93(d,J＝9.6Hz,1H,pyridazinyl-6-H),5.26(d,J＝7.5Hz,1H,NH),4.24– 4.39(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.12–3.26(m,2H,piperidyl-2,6-2H),2.46(s,3H, CCH 3 ),2.14–2.21(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H).
Compound 80-1-4, melting point 140.3 deg.C. Delta (CDCl) 3 ):8.30(s,1H,pyrimidyl-2-H),7.20(d,J＝9.6Hz,1H, pyridazinyl-4-H),6.93(d,J＝9.6Hz,1H,pyridazinyl-6-H),4.83(d,J＝7.5Hz,1H,NH),4.25– 4.37(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.14–3.23(m,2H,piperidyl-2,6-2H),2.69(q,J＝ 7.6Hz,2H,CH 2 CH 3 ),2.14–2.23(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H), 1.25(t,J＝7.6Hz,3H,CH 2 CH 3 ).
Compound 81-4, oil. Delta (CDCl) 3 ):8.54(s,1H,pyrimidyl-2-H),7.21(d,J＝9.6Hz,1H, pyridazinyl-4-H),6.94(d,J＝9.6Hz,1H,pyridazinyl-6-H),6.70(t,J＝53.7Hz,1H,CHF 2 ),5.50 (d,J＝7.5Hz,1H,NH),4.31–4.40(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.15–3.24(m,2H, piperidyl-2,6-2H),2.15–2.24(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H).
Compound 91-4, melting point 101.3 ℃. Delta (CDCl) 3 ):8.41(s,1H,pyrimidyl-2-H),8.10(d,J＝2.3Hz,1H, pyrazinyl-6-H),7.89(d,J＝2.3Hz,1H,pyrazinyl-5-H),5.24(d,J＝7.5Hz,1H,NH),4.25–4.37 (m,3H,piperidyl-CH+piperidyl-2,6-2H),3.14–3.23(m,2H,piperidyl-2,6-2H),2.78(q,J＝7.6Hz, 2H,CH 2 CH 3 ),2.14–2.21(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H),1.25(t, J＝7.6Hz,3H,CH 2 CH 3 ).
Compound 92-4 melting point 117.3 ℃. Delta (CDCl) 3 ):8.54(s,1H,pyrimidyl-2-H),8.10(d,J＝2.3Hz,1H, pyrazinyl-6-H),7.89(d,J＝2.3Hz,1H,pyrazinyl-5-H),6.70(t,J＝53.7Hz,1H,CHF 2 ),5.50(d,J ＝7.5Hz 1H,NH),4.31–4.40(m,3H,piperidyl-CH+piperidyl-2,6-2H),3.15–3.24(m,2H, piperidyl-2,6-2H),2.15–2.24(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H).
Compounds 91-1-4 are oils. Delta (CDCl) 3 ):8.30(s,1H,pyrimidyl-2-H),8.10(d,J＝2.3Hz,1H, pyrazinyl-6-H),7.89(d,J＝2.3Hz,1H,pyrazinyl-5-H),4.83(d,J＝7.5Hz,1H,NH),4.25–4.37 (m,3H,piperidyl-CH+piperidyl-2,6-2H),3.14–3.23(m,2H,piperidyl-2,6-2H),2.69(q,J＝7.6Hz, 2H,CH 2 CH 3 ),2.14–2.21(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H),1.25(t, J＝7.6Hz,3H,CH 2 CH 3 ).
Compound 90-4, oil. Delta (CDCl) 3 ):8.37(s,1H,pyrimidyl-2-H),8.10(d,J＝2.3Hz,1H, pyrazinyl-6-H),7.89(d,J＝2.3Hz,1H,pyrazinyl-5-H),5.26(d,J＝7.5Hz,1H,NH),4.24–4.39 (m,3H,piperidyl-CH+piperidyl-2,6-2H),3.12–3.26(m,2H,piperidyl-2,6-2H),2.46(s,3H,CCH 3 ), 2.14–2.21(m,2H,piperidyl-3,5-2H),1.53–1.61(m,2H,piperidyl-3,5-2H).
The melting point of the compound 47-1-44 is 135.2 ℃. Delta (CDCl) 3 ):8.71(d,J＝2.7Hz,1H,phenyl-3-H),8.30(s,1H, pyrimidyl-2-H),8.26(dd,J＝9.3,2.7Hz,1H,phenyl-5-H),7.14(d,J＝9.3Hz,1H,phenyl-6-H), 5.29(d,J＝7.5Hz 1H,NH),4.23–4.35(d,J＝7.1Hz,1H,piperidyl-CH),3.51(d,J＝13.3Hz,2H, piperidyl-2,6-2H),3.19–3.29(m,2H,piperidyl-2,6-2H),2.81(q,J＝7.6Hz,2H,CH 2 CH 3 ),2.20– 2.26(m,2H,piperidyl-3,5-2H),1.70–1.81(m,2H,piperidyl-3,5-2H),1.26(t,J＝7.6Hz,3H, CH 2 CH 3 ).
Compounds 47-1-136, mp 186.9 ℃. Delta (CDCl) 3 ):8.31(s,1H,pyrimidyl-2-H),7.61(s,1H, phenyl-3-H),7.46(d,J＝8.3Hz,1H,phenyl-5-H),7.09(d,J＝8.3Hz,1H,phenyl-6-H),4.89(d,J ＝6.5Hz 1H,NH),4.13–4.23(m,1H,piperidyl-CH),3.46(d,J＝11.6Hz,2H,piperidyl-2,6-2H), 2.89(t,J＝11.5Hz,2H,piperidyl-2,6-2H),2.71(q,J＝7.5Hz,2H,CH 2 CH 3 ),2.20(d,J＝12.0Hz, 2H,piperidyl-3,5-2H),1.70–1.81(m,2H,piperidyl-3,5-2H),1.26(t,J＝7.6Hz,3H,CH 2 CH 3 ).
Examples of measurement of biological Activity
The compound of the invention shows good activity to various germs, pests and mites in the agricultural field.
Example 9: measurement of fungicidal Activity
The compound sample of the invention is used for carrying out in vitro bacteriostatic activity or in vivo protection effect tests on various fungal diseases of plants. The results of the bactericidal activity measurements are given in the examples below.
Living body protecting Activity assay
The measurement method is as follows: the living potted plant determination method is adopted, i.e. a compound sample to be detected 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, the volume ratio of the solvent amount to the liquid spraying amount is equal to or less than 0.05), and the solution to be detected is prepared by diluting with water containing 0.1 percent of Tween 80. The solution to be tested is sprayed on disease 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 compound disease control effect evaluation is carried out after the control is sufficiently ill (usually, one week).
(1) The results of the in vivo protective activity test of some compounds are as follows:
in vivo protective activity against cucumber downy mildew:
at a dose of 400ppm, the control effect of the compound shown in the general formula I on cucumber downy mildew is more than 80%, wherein partial compounds: 15-16, 13-16, 14-16, 15-1, 15-18, 13-18, 14-153, 14-48, 48-40, 46-40, 47-163, 48-163, 46-163, 47-44, 48-44, 46-44, 14-2, 14-31, 15-50, 25-16, 14-106, 13-106, 15-106, 14-1, 15-1, 14-157, 14-1-16, 14-1-21, 91-1-4, 92-4, 90-4, 58-1-25, 8-1-4, 58-25, 80-24, 79-4, 81-4, 59-25, 57-25, 91-4, 47-1-44, 47-1-136 and the like have a 100% of downy mildew prevention effect;
at a dose of 100ppm, compound: 15-16, 13-16, 14-16, 15-1, 15-18, 13-18, 14-18, 48-4, 47-163, 48-163, 46-163, 47-44, 48-44, 14-106, 15-1, 80-24, 79-4, 57-25, 91-1-4, 9-0, 58-25, 59-25, 91-4, 14-1-157, 14-1-16, 14-1-21 and the like have 100 percent of control effect on cucumber downy mildew;
at a dose of 25ppm, compound: 15-16, 13-16, 14-16, 15-1, 15-18, 47-163, 48-163, 47-4, 48-44, 80-24, 79-4, 59-25, 57-25, 91-4 and the like have the control effect on cucumber downy mildew of more than 95 percent, and the control effect of the compound CK1 on cucumber downy mildew is 90 percent.
At a dose of 6.25ppm, compound: 15-16, 13-16, 14-16, 15-18, 47-44, 80-24, 79-4, 57-25, 91-4 and the like have the control effect on cucumber downy mildew of more than 80 percent, and the control effect of the compound CK1 on the cucumber downy mildew is 20 percent.
In vivo protective activity against wheat powdery mildew:
at a dose of 400ppm, compound: 15-16, 14-16, 15-1, 15-18, 14-2, 14-31, 14-50, 15-50, 25-16, 91-4, 47-1-44 and the like have 100% of control effect on wheat powdery mildew, and the control effect of the compound CK1 on wheat powdery mildew is also 100%;
at a dose of 100ppm, compound: 15-16, 14-2, 25-16, 47-1-44 and the like have the control effect on wheat powdery mildew of more than 80 percent, and the control effect of the compound CK1 on the wheat powdery mildew is 0;
in vivo protective activity against cucumber anthracnose:
at a dose of 400ppm, compound: the control effect of 13-18, 14-18, 47-161, 47-163, 48-163, 46-163, 47-44, 46-44, 14-19, 15-50, 13-50, 14-17, 15-17 and the like on cucumber anthracnose is more than 80%, and the control effect of the compound CK1 on cucumber anthracnose is 40%.
(2) Test results for partial Compounds and control Agents
A comparison of the activity of some of the compounds with that of the control agents was performed and the results are shown in tables 115-117
TABLE 115 control of cucumber downy mildew
Figure BDA0002747185910000521
TABLE 116 prevention of wheat powdery mildew
Figure BDA0002747185910000522
Figure BDA0002747185910000531
Note: "//" indicates not tested, the same applies below.
TABLE 117 control of cucumber anthracnose
Figure BDA0002747185910000532
Example 10: determination of insecticidal and acaricidal Activity
Several insects were tested for insecticidal activity using the compounds of the present invention. The measurement method is as follows:
the test compound was dissolved in a mixed solvent of acetone/methanol (1:1) and then diluted with water containing 0.1% (wt) tween 80 to the desired concentration.
The insecticidal activity is determined by taking plutella xylostella, myzus persicae and tetranychus cinnabarinus as targets and adopting an airrbrush spraying method.
(1) Activity assay for killing 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 0.5ml. 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. After treatment, the mixture is placed into an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% for culture, the number of the survival insects is investigated after 72 hours, and the mortality is calculated.
Partial test results for plutella xylostella are as follows:
at the dose of 600ppm, the lethality of the compounds 14-156, 46-136, 47-136, 48-136, 14-2, 13-50, 14-50, 15-50, 14-17, 15-17, 14-19, 15-19, 14-1-21, 81-4, 58-25, 92-4, 79-4, 57-25, 59-25, 90-4, 80-24 and the like to the plutella xylostella is more than 80%, while the lethality of the control compounds CK1, CK2, CK3, CK6 and CK7 to the plutella xylostella is 0.
(2) Activity measurement for killing 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 0.5ml. After 3 times of treatment, the treated mites were placed in a standard observation room, and the number of live mites was checked after 72 hours to calculate the mortality rate.
The results of the partial tests on tetranychus cinnabarinus are as follows:
the compounds with the lethality rate of more than 80 percent to tetranychus cinnabarinus at the dose of 600ppm comprise 13-21, 14-21, 15-21, 13-157, 14-157, 15-157, 14-156, 10-157, 46-136, 47-136, 48-136, 58-69, 14-1, 14-106, 25-16, 14-19, 14-50, 14-2, 14-31, 14-1-157, 47-1-136, 94-1, 92-4, 58-25 and the like;
the compounds with the lethality rate of more than 80 percent to tetranychus cinnabarinus at the dose of 100ppm comprise 13-21, 14-21, 15-21, 13-157, 14-157, 15-157, 14-156, 46-136, 47-136, 48-136, 58-69, 14-50, 14-2, 14-31, 14-1-157, 47-1-136, 92-4 and the like;
the compounds with the fatality rate of more than 80 percent to tetranychus cinnabarinus at the dosage of 10ppm comprise 14-21, 13-157, 14-157, 15-157, 46-136, 47-136, 48-136, 14-1-157, 47-1-136 and the like;
under the dosage of 5ppm, the lethality of the compounds 14-21, 14-157, 15-157, 46-136, 47-136, 48-136, 14-1-157 and 47-1-136 to tetranychus cinnabarinus is more than 80%.
(3) Activity measurement of aphid persicae killer
The measuring 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) cutting cabbage leaves with proper size (diameter of about 3 cm) and 15-30 aphids from cabbage plants for culturing the green peach aphids, removing the winged aphids and the aphids on 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/cm 2) and a liquid spray volume of 0.5ml, and the treatment was repeated 3 times. After treatment, the mixture is placed into an observation room with the temperature of 25 ℃ and the relative humidity of 60-70% for culture, the number of the survival insects is investigated after 48 hours, and the death rate is calculated.
The compounds with the lethality rate of more than 80 percent on the green peach aphid under the dosage of 600ppm comprise 14-2, 14-31, 14-50, 15-50, 14-19, 15-19, 14-1, 80-4, 79-4 and the like.
(4) Test results for partial Compounds and control Agents
Activity comparisons of some compounds with control agents were performed and the results are shown in tables 118-119 (in tables "///" indicates no test).
TABLE 118 control of plutella xylostella
Figure BDA0002747185910000541
/>
Figure BDA0002747185910000551
TABLE 119 control of Tetranychus cinnabarinus
Figure BDA0002747185910000552
/>

Claims (4)

1. A piperidine amine compound containing pyrimidine, characterized in that: the piperidine amine compound containing pyrimidine is a compound shown as general formula I-1A, I-1B, I-1D, I-1E, I-1G and I-1H;
Figure FDA0003963587520000011
wherein the content of the first and second substances,
w is hydrogen;
when the pyrimidine-containing piperidinamine compound is of the general formula I-1A, R1 is methyl, R2 is chloro, (R) 4 ) n is selected from 3-Cl, 5-Cl and 3-NO 2 (ii) a Or R1 is ethyl, R2 is chloro, (R 4 ) n is selected from 3-F, 3-Cl, 4-Cl, 6-Cl, 3-NO 2 、3,5-2Cl、3-Cl-5-CH 3 、3-Cl-5-CF 3 (ii) a Or R1 is ethyl, R2 is fluoro, (R) 4 ) n is 3-Cl-5-CF 3 3,5-2Cl; or R1 is difluoromethyl, R2 is chloro, (R) 4 ) n is selected from 3-Cl, 4-Cl, 5-Cl, 6-Cl, 3-NO 2 、3-Cl-5-CF 3 ；
When the pyrimidine-containing piperidine amine compound is of the general formula I-1B, R1 is ethyl, R2 is chloro, (R 4 ) n is 2-Cl;
when the pyrimidine-containing piperidine amine compound is of the general formula I-1D, R1 is methyl, R2 is chloro, (R 4 ) n is 2-Cl-4-CF 3 (ii) a Or R1 is ethyl, R2 is chloro, (R 4 ) n is 2,4-2NO 2 、2-NO 2 -3-Cl、2-NO 2 -5-CH 3 、2-Cl-4-CF 3 (ii) a Or R1 is ethyl, R2 is fluoro, (R) 4 ) n is 2,4-2NO 2 、2-Cl-4-CF 3 (ii) a Or R1 is difluoromethyl, R2 is chloro, (R) 4 ) n is selected from 2-NO 2 -3-Cl、2-NO 2 -5-CH 3 、2-Cl-4-CF 3 ；
When the pyrimidine-containing piperidine amine compound is of the general formula I-1E, R1 is selected from methyl, ethyl, difluoromethyl, R2 is chloro, (R 4 ) n is selected from 6-Cl;
when the pyrimidine-containing piperidinamine compound is of the formula I-1G, R1 is methyl, R2 is chloro, (R 4 ) n is 6-Cl; or R1 is ethyl, R2 is chloro, (R 4 ) n is 4-Cl-5-NHCOCH 3 (ii) a Or R1 is difluoromethyl, R2 is chloro, (R) 4 ) n is 6-Cl;
when the pyrimidine-containing piperidine amine compound is of the general formula I-1H, R1 is selected from methyl, ethyl, difluoromethyl, R2 is chloro, (R 4 ) n is 3-Cl.
2. Use of the pyrimidine-containing piperidine amine compound according to claim 1 for the preparation of a bactericide, insecticide, acaricide, or the like in agriculture or other fields.
3. The bactericidal, insecticidal and acaricidal composition is characterized by comprising the following components in parts by weight: containing the pyrimidine-containing piperidinamines as claimed in claim 1 as an active ingredient; wherein, the weight percentage of the active components in the composition is 0.1 to 99 percent.
4. Use of a composition according to claim 3 for controlling germs, pests and mites in the agricultural field.
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DE4208254A1 (en) * 1992-03-14 1993-09-16 Hoechst Ag SUBSTITUTED PYRIMIDINE, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS A PEST CONTROL AND FUNGICIDE
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