CN111825661B - 噁唑酰胺类化合物及其制备方法和应用、一种杀菌剂 - Google Patents
噁唑酰胺类化合物及其制备方法和应用、一种杀菌剂 Download PDFInfo
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- CN111825661B CN111825661B CN202010313745.9A CN202010313745A CN111825661B CN 111825661 B CN111825661 B CN 111825661B CN 202010313745 A CN202010313745 A CN 202010313745A CN 111825661 B CN111825661 B CN 111825661B
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- -1 Oxazole amide compound Chemical class 0.000 title claims abstract description 56
- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 25
- 239000003899 bactericide agent Substances 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 claims description 215
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- 239000007821 HATU Substances 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 229940125782 compound 2 Drugs 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 229940125904 compound 1 Drugs 0.000 claims description 3
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims description 2
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims description 2
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- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 claims description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 claims description 2
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims description 2
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 claims description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 2
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 2
- FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 claims description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims description 2
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims description 2
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 claims description 2
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims description 2
- OMBVEVHRIQULKW-DNQXCXABSA-M (3r,5r)-7-[3-(4-fluorophenyl)-8-oxo-7-phenyl-1-propan-2-yl-5,6-dihydro-4h-pyrrolo[2,3-c]azepin-2-yl]-3,5-dihydroxyheptanoate Chemical compound O=C1C=2N(C(C)C)C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=3C=CC(F)=CC=3)C=2CCCN1C1=CC=CC=C1 OMBVEVHRIQULKW-DNQXCXABSA-M 0.000 claims description 2
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 claims description 2
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 claims description 2
- OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 claims description 2
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 claims description 2
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims description 2
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 claims description 2
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims description 2
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims description 2
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 claims description 2
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 claims description 2
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 claims description 2
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 claims description 2
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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Abstract
本发明涉及农药领域，公开了噁唑酰胺类化合物及其制备方法和应用以及一种杀菌剂，该化合物具有式(I)所示的结构。本发明提供的噁唑酰胺类化合物具有良好的杀菌活性。
Description
技术领域
本发明涉及农药领域，具体涉及一种噁唑酰胺类化合物、一种制备噁唑酰胺类化合物的方法、噁唑酰胺类化合物作为杀菌剂的应用、一种杀菌剂。
背景技术
真菌是自然界的重要组成部分，我们与其朝夕相处，其也在影响着我们的生活，在科技日新月异的今天，我们仍然无法一劳永逸的解决威胁农业生产的病害问题。
真菌能寄生在植物表面或体内，有害的真菌能侵染植物，争夺消耗植物体细胞和其他组织中的营养物质进行大量繁殖，进而导致植物由于不能获得足够的能量而死亡。
以棉花，小麦，水稻，玉米，大豆为代表的农作物和以黄瓜，葡萄，番茄，马铃薯为代表的蔬菜瓜果一旦受到致病真菌的侵染，轻则导致产品质量不佳，重则导致作物大面积死亡而绝收。
有害的致病真菌包括低等真菌和高等真菌两类，低等致病真菌主要由鞭毛菌亚门和结合菌亚门引发，将导致霜霉病、晚疫病、猝倒病、根腐病、根肿病、马铃薯粉痂病及甘薯软腐病等。高等致病真菌主要由半知菌亚门、子囊菌和担子菌亚门构成，能导致如炭疽病、灰霉病、白粉病、立枯病、根腐病、褐斑病、纹枯病、赤霉病、锈病、枯萎病、菌核病、蔓枯病、黄萎病、苹果腐烂病、梨黑星病、甘薯黑斑病、禾谷类黑粉黑穗病等。
现有技术中已经有许多十分优秀的杀菌剂品种，如嘧菌酯，噁唑菌酮，氟噻唑吡乙酮等等，但是由于长期不合理的使用和气候变暖等诸多环境因素影响，绝大部分杀菌剂的作用靶点已经出现了大量基因突变，导致大量抗性菌种的出现，为此，需要开发新的杀菌剂以实现好的杀菌效果。
发明内容
本发明的目的是为了提供一种具有广谱抑菌和杀菌活性的新的噁唑酰胺类化合物。
为了实现上述目的，本发明的第一方面提供一种噁唑酰胺类化合物，该化合物具有式(I)所示的结构，
其中，在式(I)中，
R21、R22、R23、R24和R25各自独立地选自H、卤素、C1-12的烷基、C1-12的烷氧基、由1-3个卤素取代的C1-12的烷基、由取代或未取代的苯基取代的C7-12的烷基、由取代或者未取代的苯氧基取代的C7-12的烷基、由1-3个卤素取代的C1-12的烷氧基、由C1-3的烷氧基取代的C2-12的烷氧基、硝基、氰基、C2-12的烷羰基、C2-6的烷氧羰基、C2-6的烯基、C2-6的炔基、由1-10个卤素取代的C3-6的饱和或不饱和环基、含有选自S、O、N、P和Si中的至少一种杂原子的由1-10个卤素取代的C3-6饱和或不饱和环基、式(I1)所示的基团中的至少一种，且R21、R22、R23、R24和R25中的至少一个为式(I1)所示的基团；
R31选自C1-6的烷基、C2-6的烯基、取代或未取代的吗啉基、取代或未取代的苯基、取代或未取代的吡咯基、取代或未取代的呋喃基、取代或未取代的噻吩基、取代或未取代的嘧啶基、取代或未取代的吡啶基、取代或未取代的吡嗪基、由苯基取代的C7-12的烷基、由氯苯基取代的C7-12的烷基、由溴苯基取代的C7-12的烷基、由氰基苯基取代的C8-13的烷基，且该R31中任选含有的取代基各自独立地选自卤素、C1-6的烷基、C1-6的烷氧基、由1-3个卤素取代的C1-6的烷基、由1-3个卤素取代的C1-6的烷氧基、苯基、苯氧基、苄基、氯苯基、氰基苯氧基、羟基、硝基和氰基中的至少一种；
R32选自H、卤素、C1-6的烷基、C1-6的烷氧基、由1-3个卤素取代的C1-6的烷基、由1-3个卤素取代的C1-6的烷氧基、硝基、氰基、取代或未取代的苯基、C1-6的烷基硝基、C2-6的烷基氰基、C2-6的烷羰基、C2-6的烷氧羰基、C2-6的烯基、C2-6的炔基、由1-10个卤素取代的C3-6的饱和或不饱和环基、含有选自S、O、N、P和Si中的至少一种杂原子的由1-10个卤素取代的C3-6饱和或不饱和环基、取代或未取代的C5-10的芳香环基、取代或未取代的含有选自S、O、N、P和Si中的至少一种杂原子的C5-10的环基中的至少一种；
R4为H、C1-6的烷基、C1-6的烷氧基、C1-6的烷硫基、由1-3个卤素取代的C1-6的烷基或由1-3个卤素取代的C1-6的烷氧基；
其中，在R21、R22、R23、R24、R25和R32中，任选存在的取代基选自卤素、C1-6的烷基、C1-6的烷氧基、由1-3个卤素取代的C1-6的烷氧基、硝基、氰基、苯基、C2-6的烷羰基、C2-6的烷氧羰基、C2-6的烯基、C2-6的炔基中的至少一种；
其中，在式(I1)中，R11、R12、R13、R14和R15各自独立地选自H、卤素、C1-12的烷基、C1-12的烷氧基、由1-3个卤素取代的C1-12的烷基、由1-3个卤素取代的C1-12的烷氧基、C2-6的烷羰基、C2-6的烷氧羰基、C2-6的烯基、C2-6的炔基、由1-10个卤素取代的C3-6的饱和或不饱和环基、含有选自S、O、N、P和Si中的至少一种杂原子的由1-10个卤素取代的C3-6饱和或不饱和环基、硝基和氰基中的至少一种，或者R11、R12、R13、R14和R15中的任意相邻两个基团一起形成不含有或者含有选自N和/或O的杂原子的饱和或者不饱和的5-6元环。
本发明的“卤素”表示氟、氯、溴和碘元素。
“C2-12的烷羰基”表示碳原子总数为2-12，且结构可以表示为-COR1，其中R1为烷基。
“C2-6的烷氧羰基”表示碳原子总数为2-6，且结构可以表示为-COOR2，其中R2为烷基。
“C1-12的烷基”表示碳原子数为1-12的烷基，包括直链烷基、支链烷基和环烷基，例如可以为甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙基、甲基环丙基、乙基环丙基、环戊基、甲基环戊基或环己基等。
“C1-12的烷氧基”与“C1-12的烷基”具有相似的定义，表示碳原子数为1-12的烷氧基，包括直链烷氧基、支链烷氧基和环烷氧基，例如可以为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、叔丁氧基、正戊氧基、异戊氧基、正己氧基、环丙氧基、甲基环丙氧基、乙基环丙氧基、环戊氧基、甲基环戊氧基或环己氧基等。
“由1-3个卤素取代的C1-12的烷基”与“C1-12的烷基”具有相似的定义，所不同的是，“由1-3个卤素取代的C1-12的烷基”表示“C1-12的烷基”上的1-3个氢原子由卤素取代。
“由1-3个卤素取代的C1-12的烷氧基”与“C1-12的烷氧基”具有相似的定义，所不同的是，“由1-3个卤素取代的C1-12的烷氧基”表示“C1-12的烷氧基”上的1-3个氢原子由卤素取代。
“C1-6的烷基”与“C1-12的烷基”具有相似的定义，所不同的是，“C1-6的烷基”的碳原子总数为1-6个。例如可以为甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙基、甲基环丙基、乙基环丙基、环戊基、甲基环戊基、环己基。
“C1-6的烷氧基”与“C1-12的烷氧基”具有相似的定义，所不同的是，“C1-6的烷氧基”的碳原子总数为1-6个。例如可以为甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、异丁氧基、叔丁氧基、正戊氧基、异戊氧基、正己氧基、环丙氧基、甲基环丙氧基、乙基环丙氧基、环戊氧基、甲基环戊氧基、环己氧基。
“由1-3个卤素取代的C1-6的烷基”与“由1-3个卤素取代的C1-12的烷基”具有相似的定义，所不同的是，“由1-3个卤素取代的C1-6的烷基”的碳原子总数为1-6个。
“C1-3的烷基”与“C1-12的烷基”具有相似的定义，所不同的是，“C1-3的烷基”的碳原子总数为1-3个。例如包括甲基、乙基、正丙基、异丙基、环丙基。
“C1-3的烷氧基”与“C1-12的烷氧基”具有相似的定义，所不同的是，“C1-3的烷氧基”的碳原子总数为1-3个。例如包括甲氧基、乙氧基、正丙氧基、异丙氧基、环丙氧基。
“由取代或未取代的苯基取代的C7-12的烷基”表示该基团的碳原子总数为7-12，且该碳原子总数中包括了苯基的碳原子数，其结构可以表示为-R3-Ph-W1，其中，R3表示烷基基团，且该烷基基团上的至少一个H被苯基取代，该苯基上任选存在取代基W1，W1选自前文中定义的基团。“由苯基取代的C7-12的烷基”、“由氯苯基取代的C7-12的烷基”、“由溴苯基取代的C7-12的烷基”与此有相似的定义。
“由取代或者未取代的苯氧基取代的C7-12的烷基”表示该基团的碳原子总数为7-12，且该碳原子总数中包括了苯氧基的碳原子数，其结构可以表示为-R4-OPh-W2，其中，R4表示烷基基团，且该烷基基团上的至少一个H被苯氧基取代，该苯氧基上任选存在取代基W2，W2选自前文中定义的基团。
“由氰基苯基取代的C8-13的烷基”表示该基团的碳原子总数为8-13，且该碳原子总数中包括了氰基取代的苯基的碳原子数，其结构可以表示为-R5-Ph-CN，R5表示烷基基团。
“氯苯基”表示-Ph-Cl所示的结构。
“氰基苯氧基”表示-OPh-CN所示的结构。
根据一种更优选的具体实施方式，在式(I)中，
R21、R22、R23、R24和R25中的任意一个为式(I1)所示的基团，其余均为H；
R11、R12、R13、R14和R15各自独立地选自H、卤素、由1-3个卤素取代的C1-12的烷基、硝基、C1-12的烷基、由1-3个卤素取代的C1-12的烷氧基、氰基、C1-12的烷氧基，或者R11、R12、R13、R14和R15中的任意相邻两个基团一起形成不含有或者含有选自N和/或O的杂原子的饱和或者不饱和的5-6元环；
R31选自C1-6的烷基、C2-6的烯基、取代或未取代的吗啉基、取代或未取代的嘧啶基、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的吡嗪基、由苯基取代的C7-12的烷基、由溴苯基取代的C7-12的烷基、由氯苯基取代的C7-12的烷基、由氰基苯基取代的C8-13的烷基、-NHR5，R5选自取代或未取代的苯基；
且该R31和R5中任选含有的取代基各自独立地选自卤素、C1-6的烷基、C1-6的烷氧基、由1-3个卤素取代的C1-6的烷基、苯基、苯氧基、硝基和氰基中的至少一种；
R32选自H、由1-3个卤素取代的C1-6的烷基、C1-6的烷基、C1-6的烷氧基和取代或未取代的苯基；R32中任选存在的取代基各自独立地选自卤素、C1-6的烷氧基中的至少一种；
R4为H、C1-6的烷基、C1-6的烷氧基或C1-6的烷硫基。
根据另一种更优选的具体实施方式，在式(I)中，
R21、R22、R23、R24和R25中的任意一个为式(I1)所示的基团，其余均为H；
R11、R12、R13、R14和R15各自独立地选自H、卤素、由1-3个卤素取代的C1-6的烷基、硝基、C1-6的烷基、由1-3个卤素取代的C1-6的烷氧基、氰基、C1-6的烷氧基，或者R11、R12、R13、R14和R15中的任意相邻两个基团一起形成不含有或者含有选自N和/或O的杂原子的饱和或者不饱和的5-6元环；
R31选自C1-4的烷基、C2-4的烯基、取代或未取代的吗啉基、取代或未取代的嘧啶基、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的吡嗪基、由苯基取代的C7-12的烷基、由溴苯基取代的C7-12的烷基、由氯苯基取代的C7-12的烷基、由氰基苯基取代的C8-13的烷基、-NHR5，R5选自取代或未取代的苯基；
且该R31和R5中任选含有的取代基各自独立地选自卤素、C1-6的烷基、C1-6的烷氧基、由1-3个卤素取代的C1-6的烷基、苯基、苯氧基、硝基和氰基中的至少一种；
R32选自H、由1-3个卤素取代的C1-3的烷基、C1-3的烷基、C1-3的烷氧基和取代或未取代的苯基；R32中任选存在的取代基各自独立地选自卤素、C1-3的烷氧基中的至少一种；
R4为H、C1-3的烷基、C1-3的烷氧基或C1-3的烷硫基。
根据一种特别优选的具体实施方式，本发明的所述噁唑酰胺类化合物选自权利要求4所列的具体化合物中的至少一种。
本发明对制备所述噁唑酰胺类化合物的具体方法没有特别的限定，本领域技术人员可以根据本发明提供的结构式，结合有机合成领域内的常规技术手段获得前述噁唑酰胺类化合物的具体制备方法。
为了获得更高的收率，本发明的第二方面提供一种制备式(I)所示的噁唑酰胺类化合物的方法，该方法包括：在缩合剂存在下，将式(III)所示的化合物与式(II)所示的化合物进行接触反应，
其中，在式(I)、式(II)和式(III)中的各取代基的定义分别与前述第一方面中的定义对应相同。
本发明第二方面中涉及的式(I)所示的噁唑酰胺类化合物与前述第一方面中涉及的式(I)所示的噁唑酰胺类化合物结构完全相同，因此，本发明第二方面中涉及的式(I)、式(II)和式(III)中的各个取代基的具体情况均与本发明的第一方面中所述相同，为了避免赘述，本发明在此不再一一列举。
优选情况下，所述缩合剂包括HATU(2-(7-氧化苯并三氮唑)-N,N,N',N'-四甲基脲六氟磷酸盐)和DIPEA(N,N-二异丙基乙胺)。
优选地，所述HATU和所述DIPEA的用量摩尔比为1：(0.3-1.5)。
根据一种优选的具体实施方式，所述接触反应的条件包括：温度为0-60℃，时间为0.5-48h。
本发明所述制备方法中还可以包括本领域常用的各种后处理操作，例如洗涤、过滤、柱层析等等。
本发明的所述式(II)和式(III)所示的化合物可以通过商购获得，也可以通过采用现有技术的方法合成获得，本发明的后文中示例性地提供了一种制备式(II)和/或式(III)所示的化合物的方法，本领域技术人员不应理解为对本发明的限制。
本发明的前述制备方法优选在有机溶剂存在下进行，本发明对有机溶剂的具体种类没有特别的限定，可以为任意能够溶解前述原料的溶剂。
本发明的第三方面提供前述第一方面或第四方面所述的噁唑酰胺类化合物作为杀菌剂的应用。
本发明提供的所唑酰胺类化合物具有优异的杀菌效果，例如对卵菌、子囊菌、担子菌、半知菌等真菌均具有良好的杀菌效果，特别是对真菌(例如引起水稻纹枯病、黄瓜霜霉病、瓜类白粉病、大豆锈病、玉米锈病、颖枯病、网斑病和小麦白粉病的真菌)具有优异的杀菌效果。
本发明的第四方面提供一种杀菌剂，该杀菌剂中含有活性成分和辅料，所述活性成分包括前述的噁唑酰胺类化合物中的至少一种。
根据一种优选的具体实施方式，所述活性成分的含量为1-99.9重量％，。
优选情况下，该杀菌剂的剂型选自可湿性粉剂、悬浮剂、水乳剂和水分散粒剂中的至少一种。
优选地，该杀菌剂中还含有安全剂。所述安全剂可以为本领域内常规使用的各种安全剂。
具体实施方式
在本文中所披露的范围的端点和任何值都不限于该精确的范围或值，这些范围或值应当理解为包含接近这些范围或值的值。对于数值范围来说，各个范围的端点值之间、各个范围的端点值和单独的点值之间，以及单独的点值之间可以彼此组合而得到一个或多个新的数值范围，这些数值范围应被视为在本文中具体公开。
以下提供一种优选的具体实施方式的合成路线制备本发明的化合物1：
(1)在250mL圆底烧瓶中加入式a2所示的化合物(异氰基乙酸乙酯)(88.4mmol)，加入50mL四氢呋喃溶解，10℃下加入DBU(88.4mmol)，再逐滴加入50mL溶有式a1所示的化合物(二氟乙酸酐)(176.8mmol)的四氢呋喃溶液，滴加完全后，25℃反应10h。反应完全后，减压除去溶剂后，进行柱色谱层析得到中间体a3所示的化合物。
(2)在100mL两口烧瓶中加入中间体a3所示的化合物(5-二氟甲基噁唑-4-甲酸乙酯)(7.1mmol)，三(二亚苄基丙酮)二钯(0.355mmol)，4,5-双二苯基膦-9,9-二甲基氧杂蒽(0.355mmol)，碳酸铯(14.2mmol)，氮气保护下，加入2-氯嘧啶7.1mmol，完毕后，加入20mL乙二醇二甲醚溶解，90℃加热回流反应，TLC检测反应完全后，反应体系加入20mL水，20ml乙酸乙酯萃取三次，合并有机相，加入无水硫酸钠干燥，减压除去溶剂后，再进行柱色谱层析得到中间体a4所示的化合物。
(3)取100mL梨形瓶，向其中加入中间体a4(2mmol)，随后加入10mL THF使其溶解，向体系内加入LiOH·H2O(4mmol)，再加入5mL水。室温下搅拌，利用TLC板点板监测反应，待反应完全后，减压旋干体系内溶剂，通过加入2N稀盐酸调节pH为2-3，析出白色固体，过滤析出的白色固体，移入红外干燥箱内，干燥完毕后即得中间体a5,可直接参与下一步反应。
(4)向50ml梨形瓶中加入0.52mmol中间体a5所示的化合物，HATU(0.8mmol)和DIPEA(0.8mmol)，加入15ml二氯甲烷溶解，25℃反应8h，加入0.4mmol取代的4-苯氧基苯胺，TLC监测反应完全后，减压旋出溶剂，柱色谱层析即可得化合物1。
以下提供另一种优选的具体实施方式的合成路线制备本发明的例如化合物2：
(1)在100mL两口烧瓶中加入b1所示的化合物(4-噁唑甲酸乙酯)(7.1mmol)，三(二亚苄基丙酮)二钯(0.355mmol)，4,5-双二苯基膦-9,9-二甲基氧杂蒽(0.355mmol)，碳酸铯(14.2mmol)，氮气保护下，加入b2所示的化合物(取代的碘苯)7.1mmol，完毕后，加入20ml乙二醇二甲醚溶解，90℃加热回流反应，TLC检测反应完全后，反应体系加入20mL水，20mL乙酸乙酯萃取三次，合并有机相，加入无水硫酸钠干燥，减压除去溶剂后，再进行柱色谱层析得到中间体b3所示的化合物。
(2)取100mL梨形瓶，向其中加入中间体b3(2mmol)，随后加入10mL THF使其溶解，向体系内加入LiOH·H2O(4mmol)，再加入5mL水。室温下搅拌，利用TLC板点板监测反应，待反应完全后，减压旋干体系内溶剂，通过加入2N稀盐酸调节pH为2-3，析出白色固体，过滤析出的白色固体，移入红外干燥箱内，干燥完毕后即得中间体b4,可直接参与下一步反应。
(3)向50mL梨形瓶中加入0.52mmol中间体b4所示的化合物，HATU(0.8mmol)和DIPEA(0.8mmol)，加入15mL二氯甲烷溶解，25℃反应8h，加入0.4mmol取代的4-苯氧基苯胺，TLC监测反应完全后，减压旋出溶剂，柱色谱层析即可得化合物2。
采用上述合成路线相似的方法制备本发明的其它化合物，所得化合物的表征数据具体列举如下：
化合物1：白色粉末，收率84.0％,mp＝147.9-148.9℃.1H NMR(400MHz,DMSO-d6)：δ10.89(s,1H),9.10(d,J＝4.9Hz,2H),8.04(s,1H),7.96(d,J＝8.9Hz,2H),7.79(d,J＝5.0Hz,1H),7.78–7.53(m,2H),7.17(d,J＝8.9Hz,2H),7.11(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C22H12ClF5N4O3[M+Na]+:533.0522,实测值533.0543.
化合物2：白色粉末，收率82.1％,mp＝136.9-137.7℃.1H NMR(600MHz,DMSO-d6):δ10.32(s,1H),8.92(s,1H),8.10(d,J＝8.3Hz,2H),8.03(s,1H),7.91(d,J＝8.7Hz,2H),7.68(d,J＝8.1Hz,3H),7.16(d,J＝8.6Hz,2H),7.07(d,J＝8.2Hz,1H).HRMS(MALDI)计算值C23H13Cl2F3N2O3[M+Na]+:515.0148,实测值515.0167.
化合物3：白色粉末，收率74.7％,mp＝124.8-125.4℃.1H NMR(400MHz,DMSO-d6):δ10.34(s,1H),8.96(s,1H),8.14(s,1H),8.04(s,2H),7.94(d,J＝6.1Hz,2H),7.69(s,2H),7.66(d,J＝7.6Hz,1H),7.18(d,J＝8.1Hz,2H),7.09(d,J＝8.4Hz,1H).HRMS(MALDI)计算值C23H13Cl2F3N2O3[M+Na]+:515.0148,实测值515.0151.
化合物4：白色粉末，收率87.3％,mp＝142.1-143.0℃.1H NMR(400MHz,DMSO-d6):δ10.32(s,1H),8.91(s,1H),8.22–8.10(m,2H),8.04(s,1H),7.93(d,J＝8.7Hz,2H),7.70(d,J＝8.5Hz,1H),7.47(t,J＝8.4Hz,2H),7.18(d,J＝8.6Hz,2H),7.09(d,J＝8.5Hz,1H).HRMS(MALDI)计算值C23H13ClF4N2O3[M+Na]+:499.0443,实测值499.0431.
化合物5：白色粉末，收率82.1％,mp＝110.8-111.8℃.1H NMR(400MHz,DMSO-d6):δ10.31(s,1H),8.97(s,1H),8.15(t,J＝7.6Hz,1H),8.03(s,1H),7.91(d,J＝8.8Hz,2H),7.67(m,J＝17.0,8.5Hz,2H),7.46(m,J＝11.5,8.2Hz,2H),7.17(d,J＝8.7Hz,2H),7.08(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C23H13ClF4N2O3[M+Na]+:499.0443,实测值499.0449.
化合物6：白色粉末，收率76.8％,mp＝164.0-164.7℃.1H NMR(400MHz,DMSO-d6):δ10.31(s,1H),8.98(s,1H),8.03(s,1H),7.91(d,J＝8.8Hz,2H),7.77(d,J＝5.9Hz,2H),7.69(d,J＝8.4Hz,1H),7.57(t,J＝9.3Hz,1H),7.17(d,J＝8.7Hz,2H),7.09(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C23H12ClF5N2O3[M+Na]+:517.0349,实测值517.0365.
化合物7：白色粉末，收率70.9％,mp＝188.5-189.3℃.1H NMR(400MHz,DMSO-d6):δ10.32(s,1H),8.99(s,1H),8.08(s,2H),8.03(s,1H),7.94(s,1H),7.91(d,J＝4.3Hz,2H),7.70(d,J＝9.2Hz,1H),7.18(d,J＝8.8Hz,2H),7.09(d,J＝8.8Hz,1H).HRMS(MALDI)计算值C23H12Cl3F3N2O3[M+Na]+:548.9758,实测值548.9754.
化合物8：白色粉末，收率81.4％,mp＝142.5-143.5℃.1H NMR(400MHz,DMSO-d6):δ10.36(s,1H),8.98(s,1H),8.40(s,1H),8.37(d,J＝8.2Hz,1H),8.03(s,1H),7.99(d,J＝7.8Hz,1H),7.93(d,J＝8.1Hz,2H),7.87(t,J＝7.7Hz,1H),7.70(d,J＝8.5Hz,1H),7.17(d,J＝8.1Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C24H13ClF6N2O3[M+Na]+:549.0411,实测值549.0422.
化合物9：白色粉末，收率82.0％,mp＝157.8-158.9℃.1H NMR(400MHz,DMSO-d6):δ10.32(s,1H),8.95(s,1H),8.03(s,1H),7.94(m,J＝8.2Hz,3H),7.88(d,J＝9.5Hz,1H),7.68(m,J＝17.0,8.6Hz,2H),7.48(t,J＝9.7Hz,1H),7.18(d,J＝8.8Hz,2H),7.09(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C23H13ClF4N2O3[M+H]+:477.0624,实测值477.0612.
化合物10：白色粉末，收率78.6％,mp＝114.3-115.4℃.1H NMR(400MHz,DMSO-d6):δ10.29(s,1H),8.89(s,1H),8.04(s,1H),7.95(s,2H),7.92(s,1H),7.90(d,J＝7.7Hz,1H),7.70(d,J＝8.5Hz,1H),7.49(t,J＝7.6Hz,1H),7.42(d,J＝7.3Hz,1H),7.17(d,J＝8.7Hz,2H),7.09(d,J＝8.6Hz,1H),2.43(s,3H).HRMS(MALDI)计算值C24H16ClF3N2O3[M+Na]+:495.0694,实测值495.0701.
化合物11：白色粉末，收率80.1％,mp＝116.0-116.6℃.1H NMR(400MHz,DMSO-d6):δ10.35(s,1H),8.96(s,1H),8.31(s,1H),8.25(d,J＝7.4Hz,1H),8.03(s,1H),7.93(d,J＝8.9Hz,2H),7.82(d,J＝7.5Hz,1H),7.77(t,J＝7.6Hz,1H),7.70(d,J＝8.4Hz,1H),7.28(t,J＝55.7Hz,1H),7.18(d,J＝8.9Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C24H14ClF5N2O3[M+Na]+:531.0688,实测值531.0695.
化合物12：白色粉末，收率87.4％,mp＝173.2-173.9℃.1H NMR(400MHz,DMSO-d6):δ10.42(s,1H),9.00(s,1H),8.18(d,J＝8.0Hz,1H),8.12(d,J＝7.6Hz,1H),8.03(s,1H),7.96(t,J＝7.5Hz,1H),7.91(m,J＝8.9Hz,3H),7.70(d,J＝8.6Hz,1H),7.17(d,J＝8.9Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C23H13ClF3N3O5[M+H]+:527.0592,实测值527.0585.
化合物13：白色粉末，收率81.4％,mp＝127.2-128.4℃.1H NMR(400MHz,DMSO-d6):δ10.40(s,1H),9.04(s,1H),8.13(d,J＝7.6Hz,1H),8.02(d,J＝8.7Hz,2H),7.93(m,J＝8.1Hz,3H),7.87(t,J＝7.7Hz,1H),7.70(d,J＝8.7Hz,1H),7.17(d,J＝8.8Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C24H13ClF6N2O3[M+Na]+:549.0411,实测值549.0423.
化合物14：白色粉末，收率81.6％,mp＝145.0-146.1℃.1H NMR(400MHz,DMSO-d6):δ10.33(s,1H),8.97(s,1H),8.06(d,J＝10.3Hz,1H),8.04(s,1H),7.95(d,J＝9.0Hz,1H),7.92(d,J＝8.9Hz,2H),7.87(t,J＝7.9Hz,1H),7.70(d,J＝7.9Hz,1H),7.18(d,J＝8.8Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C23H12Cl2F4N2O3[M+Na]+:533.0053,实测值533.0023.
化合物15：白色粉末，收率92.4％,mp＝125.9-126.7℃.1H NMR(400MHz,DMSO-d6):δ10.30(s,1H),8.90(s,1H),8.03(s,1H),7.93(d,J＝8.9Hz,2H),7.73–7.66(m,2H),7.62(s,1H),7.52(t,J＝8.0Hz,1H),7.21–7.14(m,3H),7.09(d,J＝8.6Hz,1H),3.87(s,3H).HRMS(MALDI)计算值C24H16ClF3N2O4[M+Na]+:511.0643,实测值511.0644.
化合物16：浅黄色粉末，收率76.2％,mp＝158.4-159.4℃.1H NMR(400MHz,DMSO-d6):δ10.29(s,1H),9.06(s,1H),8.32(d,J＝8.0Hz,1H),8.09(d,J＝7.7Hz,1H),8.03(s,1H),7.94(t,J＝7.8Hz,1H),7.89(d,J＝8.9Hz,2H),7.80(t,J＝7.7Hz,1H),7.69(d,J＝8.8Hz,1H),7.18(d,J＝8.8Hz,2H),7.09(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C24H13ClF3N3O3[M+Na]+:506.049,实测值506.0484.
化合物17：白色粉末，收率79.2％,mp＝159.8-160.3℃.1H NMR(400MHz,DMSO-d6):δ10.32(s,1H),8.99(s,1H),8.50(s,1H),8.39(d,J＝7.8Hz,1H),8.09(d,J＝7.2Hz,1H),8.03(s,1H),7.93(d,J＝8.7Hz,2H),7.84(t,J＝7.8Hz,1H),7.70(d,J＝8.7Hz,1H),7.18(d,J＝8.6Hz,2H),7.10(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C24H13ClF3N3O3[M+Na]+:506.049,实测值.506.0485。
化合物18：浅黄色粉末，收率61.5％,mp＝203.8-204.5℃.1H NMR(400MHz,DMSO-d6)：δ10.33(s,1H),9.00(s,1H),8.60(d,J＝5.8Hz,1H),8.45(dd,J＝7.1,4.5Hz,1H),8.04(s,1H),7.92(d,J＝8.8Hz,2H),7.81(t,J＝9.0Hz,1H),7.70(d,J＝8.7Hz,1H),7.18(d,J＝8.8Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C24H12ClF4N3O3[M+Na]+:524.0396,实测值524.0391.
化合物19：白色粉末，收率80.3％,mp＝119.3-120.1℃.1H NMR(400MHz,DMSO-d6):δ10.29(s,1H),8.95(s,1H),8.03(s,1H),7.97(d,J＝5.7Hz,1H),7.92(d,J＝8.9Hz,2H),7.70(d,J＝8.6Hz,1H),7.49–7.43(m,1H),7.35(dd,J＝10.7,8.7Hz,1H),7.17(d,J＝8.9Hz,2H),7.09(d,J＝8.7Hz,1H),2.40(s,3H).HRMS(MALDI)计算值C24H15ClF4N2O3[M+Na]+:513.06,实测值513.0597.
化合物20：白色粉末，收率89.1％,mp＝173.7-174.8℃.1H NMR(400MHz,DMSO-d6):δ10.30(s,1H),8.90(s,1H),8.11(dd,J＝6.1,2.4Hz,2H),8.03(s,1H),7.93(d,J＝8.8Hz,2H),7.70(d,J＝8.7Hz,1H),7.65–7.58(m,3H),7.17(d,J＝8.8Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C23H14ClF3N2O3[M+H]+:459.0718,实测值459.0719.
化合物21：白色粉末，收率93.7％,mp＝150.1-151.0℃.1H NMR(400MHz,DMSO-d6)δ10.22(s,1H),8.92(s,1H),8.13(s,1H),8.04(d,J＝7.3Hz,1H),7.80(d,J＝8.8Hz,2H),7.66(m,2H),7.36(m,3H),6.98(d,J＝8.7Hz,2H).HRMS(MALDI)计算值C22H13ClF2N2O3[M+Na]+:449.0475,实测值449.0468.
化合物22：白色粉末，收率96.5％,mp＝132.8-133.4℃.1H NMR(400MHz,DMSO-d6)δ10.24(s,1H),8.93(s,1H),8.13(s,1H),8.04(d,J＝7.0Hz,1H),7.83(d,J＝8.8Hz,2H),7.66(dt,J＝15.6,8.0Hz,2H),7.40(dt,J＝11.0,4.5Hz,1H),7.28–7.20(m,2H),7.16(dt,J＝9.5,5.7Hz,1H),7.02(d,J＝8.8Hz,2H).HRMS(MALDI)计算值C22H14ClFN2O3[M+Na]+:431.0569,实测值431.0578.
化合物23：白色粉末，收率91.1％,mp＝123.1-125.0℃.1H NMR(400MHz,DMSO-d6)δ10.28(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.87(d,J＝8.9Hz,2H),7.66(dt,J＝15.6,8.1Hz,2H),7.25(dt,J＝15.8,8.2Hz,2H),7.11(d,J＝8.9Hz,2H),6.94(t,J＝7.6Hz,1H).HRMS(MALDI)计算值C22H13ClF2N2O3[M+Na]+:449.0475,实测值449.0494.
化合物24：白色粉末，收率59.0％,mp＝157.3-158.4℃.1H NMR(400MHz,DMSO-d6)：δ10.35(s,1H),8.96(s,1H),8.27(d,J＝9.1Hz,2H),8.14(s,1H),8.05(d,J＝7.4Hz,1H),7.97(d,J＝8.8Hz,2H),7.70(d,J＝8.1Hz,1H),7.66(d,J＝7.6Hz,1H),7.23(d,J＝8.8Hz,2H),7.14(d,J＝9.1Hz,2H).HRMS(MALDI)计算值C22H14ClN3O5[M+Na]+:458.0514,实测值458.0539.
化合物25：白色粉末，收率96.1％,mp＝118.0-118.8℃.1H NMR(400MHz,DMSO-d6)δ10.28(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝6.3Hz,1H),7.89(d,J＝7.8Hz,2H),7.72–7.61(m,3H),7.08(d,J＝7.7Hz,3H),6.93(d,J＝9.6Hz,1H).HRMS(MALDI)计算值C22H13Cl2FN2O3[M+Na]+:465.018,实测值465.0186.
化合物26：白色粉末，收率68.9％,mp＝164.3-165.7℃.1H NMR(400MHz,DMSO-d6)δ10.21(s,1H),8.93(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.82(d,J＝8.8Hz,2H),7.69(d,J＝8.1Hz,1H),7.64(t,J＝7.7Hz,1H),7.19(d,J＝8.1Hz,2H),7.00(d,J＝8.8Hz,2H),6.92(d,J＝8.2Hz,2H),2.29(s,3H).HRMS(MALDI)计算值C23H17ClN2O3[M+Na]+:427.082,实测值427.0800.
化合物27：白色粉末，收率92.8％,mp＝124.6-125.3℃.1H NMR(400MHz,DMSO-d6)δ10.29(s,1H),8.95(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.89(d,J＝8.8Hz,2H),7.72–7.67(m,1H),7.65(t,J＝7.8Hz,1H),7.41(t,J＝8.1Hz,1H),7.19(d,J＝8.0Hz,1H),7.12(d,J＝8.7Hz,2H),7.04(s,1H),6.97(d,J＝8.3Hz,1H).HRMS(MALDI)计算值C22H14Cl2N2O3[M+Na]+:447.0274,实测值447.0303.
化合物28：白色粉末，收率94.3％,mp＝124.6-125.0℃.1H NMR(400MHz,DMSO-d6)δ10.24(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.3Hz,1H),7.85(d,J＝8.7Hz,2H),7.69(d,J＝7.9Hz,1H),7.65(t,J＝7.8Hz,1H),7.39(t,J＝7.7Hz,2H),7.13(t,J＝7.3Hz,1H),7.05(d,J＝8.7Hz,2H),7.01(d,J＝8.0Hz,2H).HRMS(MALDI)计算值C22H15ClN2O3[M+Na]+:413.0663,实测值413.0642.
化合物29：白色粉末，收率75.9％,mp＝152.0-153.0℃.1H NMR(400MHz,DMSO-d6)δ10.26(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.87(d,J＝8.8Hz,2H),7.69(d,J＝8.1Hz,1H),7.65(t,J＝7.8Hz,1H),7.43(d,J＝8.8Hz,2H),7.08(d,J＝8.8Hz,2H),7.03(d,J＝8.8Hz,2H).HRMS(MALDI)计算值C22H14Cl2N2O3[M+Na]+:447.0274,实测值447.0252.
化合物30：白色粉末，收率90.3％,mp＝142.1-143.0℃.1H NMR(400MHz,DMSO-d6)δ10.28(s,1H),8.94(s,1H),8.14(s,1H),8.05(d,J＝7.4Hz,1H),7.88(d,J＝8.6Hz,2H),7.69(d,J＝7.9Hz,1H),7.65(t,J＝7.8Hz,1H),7.39(d,J＝8.6Hz,2H),7.12(d,J＝5.3Hz,2H),7.09(d,J＝5.6Hz,2H).HRMS(MALDI)计算值C23H14ClF3N2O4[M+Na]+:497.0486,实测值497.0484.
化合物31：白色粉末，收率78.3％,mp＝99.6-100.1℃.1H NMR(400MHz,DMSO-d6)δ10.27(s,1H),8.91(s,1H),8.11(s,1H),8.02(d,J＝7.3Hz,1H),7.89(d,J＝8.8Hz,2H),7.66(d,J＝8.2Hz,1H),7.65–7.59(m,1H),7.49(t,J＝8.3Hz,1H),7.11(t,J＝9.7Hz,3H),6.98(d,J＝8.4Hz,1H),6.95(s,1H).HRMS(MALDI)计算值C23H14ClF3N2O4[M+Na]+:497.0486,实测值497.0486.
化合物32：白色粉末，收率64.7％,mp＝194.6-195.3℃.1H NMR(400MHz,DMSO-d6)δ10.20(s,1H),8.92(s,1H),8.12(s,1H),8.03(d,J＝7.1Hz,1H),7.77(d,J＝8.9Hz,2H),7.66(p,J＝8.0Hz,4H),7.39(t,J＝8.2Hz,1H),6.83(d,J＝8.9Hz,2H).HRMS(MALDI)计算值C22H13Cl3N2O3[M+Na]+:480.9884,实测值480.9896.
化合物33：白色粉末，收率96.6％,mp＝141.6-142.1℃.1H NMR(400MHz,DMSO-d6)δ10.33(s,1H),8.94(s,1H),8.11(s,1H),8.05(d,J＝6.6Hz,2H),7.96(d,J＝8.7Hz,2H),7.66(t,J＝9.0Hz,3H),7.20(d,J＝9.4Hz,3H).HRMS(MALDI)计算值C24H13ClF6N2O3[M+Na]+:549.0411,实测值549.0410.
化合物34：白色粉末，收率67.2％,mp＝134.8-135.3℃.1H NMR(400MHz,DMSO-d6)δ10.24(s,1H),8.90(s,1H),8.11(s,1H),8.02(d,J＝7.4Hz,1H),7.83(d,J＝8.9Hz,2H),7.70–7.65(m,1H),7.61(dd,J＝18.1,7.8Hz,2H),7.36(t,J＝7.8Hz,1H),7.23–7.17(m,1H),7.06(d,J＝8.1Hz,1H),6.99(d,J＝8.9Hz,2H).HRMS(MALDI)计算值C22H14Cl2N2O3[M+Na]+:447.0274,实测值447.0293.
化合物35：白色粉末，收率95.7％,mp＝115.8-116.7℃.1H NMR(400MHz,DMSO-d6)δ10.27(s,1H),8.88(s,1H),8.07(s,2H),7.99(d,J＝7.0Hz,1H),7.92(d,J＝8.9Hz,2H),7.69(d,J＝8.6Hz,1H),7.60(q,J＝8.2Hz,2H),7.12(d,J＝8.9Hz,2H),7.01(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C23H13BrClF3N2O3[M+Na]+:558.9812,实测值558.9823.
化合物36：白色粉末，收率70.1％,mp＝164.4-165.4℃.1H NMR(400MHz,DMSO-d6)δ10.33(s,1H),8.96(s,1H),8.14(s,1H),8.05(d,J＝7.1Hz,1H),7.94(d,J＝8.7Hz,2H),7.85(d,J＝8.5Hz,2H),7.69(d,J＝7.9Hz,1H),7.65(t,J＝7.8Hz,1H),7.19(d,J＝8.6Hz,2H),7.11(d,J＝8.5Hz,2H).HRMS(MALDI)计算值C23H14ClN3O3[M+Na]+:438.0616,实测值438.0620.
化合物37：白色粉末，收率91.6％,mp＝125.5-126.3℃.1H NMR(400MHz,DMSO-d6)δ10.31(s,1H),8.95(s,1H),8.14(s,1H),8.05(d,J＝7.4Hz,1H),7.93(d,J＝8.8Hz,2H),7.74(d,J＝8.6Hz,2H),7.69(d,J＝8.1Hz,1H),7.65(t,J＝7.8Hz,1H),7.18(d,J＝8.9Hz,2H),7.14(d,J＝8.5Hz,2H).HRMS(MALDI)计算值C23H14ClF3N2O3[M+Na]+:481.0537,实测值481.0494.
化合物38：白色粉末，收率95.5％,mp＝130.1-130.7℃.1H NMR(400MHz,CDCl3)δ8.75(s,1H),8.34(s,1H),8.10(s,1H),7.97(d,J＝7.4Hz,1H),7.67(d,J＝8.5Hz,2H),7.50(d,J＝8.0Hz,1H),7.45(t,J＝7.8Hz,1H),7.28(s,1H),7.04(d,J＝8.2Hz,1H),6.97(d,J＝8.6Hz,2H),6.92(d,J＝8.3Hz,1H),2.34(s,3H).HRMS(MALDI)计算值C23H16Cl2N2O3[M+Na]+:461.0430,实测值461.0426.
化合物39：白色粉末，收率95.4％,mp＝96.8-97.6℃.1H NMR(400MHz,CDCl3)δ8.79(s,1H),8.35(s,1H),8.10(s,1H),7.97(d,J＝7.4Hz,1H),7.73(d,J＝8.9Hz,2H),7.50(d,J＝8.0Hz,1H),7.46(t,J＝7.8Hz,1H),7.37(s,1H),7.10(d,J＝8.5Hz,1H),7.02(d,J＝8.6Hz,2H),6.97(d,J＝9.0Hz,1H).HRMS(MALDI)计算值C23H13Cl2F3N2O4[M+Na]+:531.0097,实测值531.0081.
化合物40：浅灰色粉末，收率67.0％,mp＝147.7-148.7℃.1H NMR(400MHz,DMSO-d6):δ10.51(s,1H),9.06(s,1H),9.04(d,J＝4.6Hz,2H),8.03(s,1H),7.95(d,J＝8.9Hz,2H),7.71(q,J＝10.9,6.1Hz,2H),7.16(d,J＝8.8Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C21H12ClF3N4O3[M+Na]+:483.0442,实测值483.0438.
化合物41：白色粉末，收率77.7％,mp＝169.3-170.1℃.1H NMR(400MHz,DMSO-d6):δ10.38(s,1H),8.97(s,1H),8.77(d,J＝4.4Hz,1H),8.24(d,J＝7.9Hz,1H),8.07(t,J＝7.8Hz,1H),8.03(s,1H),7.94(d,J＝8.7Hz,2H),7.70(d,J＝8.6Hz,1H),7.65–7.58(m,1H),7.17(d,J＝8.7Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C22H13ClF3N3O3[M+Na]+:482.049,实测值482.0490.
化合物42：白色粉末，收率62.1％,mp＝157.8-158.6℃.1H NMR(400MHz,DMSO-d6):δ10.35(s,1H),9.29(s,1H),8.99(s,1H),8.79(d,J＝4.7Hz,1H),8.44(d,J＝8.4Hz,1H),8.03(s,1H),7.93(d,J＝8.7Hz,2H),7.70(d,J＝8.2Hz,1H),7.65(dd,J＝7.8,4.9Hz,1H),7.18(d,J＝8.7Hz,2H),7.10(d,J＝8.8Hz,1H).HRMS(MALDI)计算值C22H13ClF3N3O3[M+H]+:460.067,实测值460.0691.
化合物43：黄色粉末，收率50.2％,mp＝189.2-189.7℃.1H NMR(400MHz,DMSO-d6):δ10.42(s,1H),9.44(s,2H),9.40(s,1H),9.07(s,1H),8.03(s,1H),7.92(d,J＝8.5Hz,2H),7.70(d,J＝8.3Hz,1H),7.18(d,J＝8.7Hz,2H),7.10(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C21H12ClF3N4O3[M+H]+:461.0623,实测值461.0612.
化合物44：白色粉末，收率60.2％,mp＝158.5-159.3℃.1H NMR(400MHz,DMSO-d6):δ10.45(s,1H),9.43(s,1H),9.07(s,1H),8.86(s,2H),8.04(s,1H),7.94(d,J＝8.8Hz,2H),7.70(d,J＝8.4Hz,1H),7.18(d,J＝8.8Hz,2H),7.10(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C21H12ClF3N4O3[M+H]+:461.0623,实测值461.0610.
化合物45：浅粉色粉末，收率87.3％,mp＝139.8-140.7℃.1H NMR(400MHz,DMSO-d6):δ10.50(s,1H),9.01(s,1H),8.88(d,J＝5.1Hz,1H),8.03(s,1H),7.95(d,J＝9.0Hz,2H),7.70(d,J＝8.7Hz,1H),7.59(d,J＝5.1Hz,1H),7.16(d,J＝9.0Hz,2H),7.09(d,J＝8.6Hz,1H),2.60(s,3H).HRMS(MALDI)计算值C22H14ClF3N4O3[M+Na]+:497.05987,实测值497.0602.
化合物46：白色粉末，收率84.2％,mp＝182.1-183.5℃.1H NMR(400MHz,DMSO-d6):δ10.52(s,1H),9.15(s,2H),9.04(s,1H),8.03(s,1H),7.95(d,J＝8.8Hz,2H),7.70(d,J＝8.2Hz,1H),7.16(d,J＝8.7Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C21H11ClF4N4O3[M+Na]+:501.0348,实测值501.0349.
化合物47：白色粉末，收率81.1％,mp＝191.9-192.8℃.1H NMR(400MHz,DMSO-d6):δ10.57(s,1H),9.43(d,J＝5.0Hz,1H),9.10(s,1H),8.24(d,J＝5.0Hz,1H),8.03(s,1H),7.95(d,J＝8.8Hz,2H),7.70(d,J＝8.5Hz,1H),7.16(d,J＝8.8Hz,2H),7.09(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C22H11ClF6N4O3[M+Na]+:551.0316,实测值551.0319.
化合物48：白色粉末，收率75.3％,mp＝204.7-205.6℃.1H NMR(600MHz,DMSO-d6):δ10.52(s,1H),9.01(s,1H),8.90(s,2H),8.04(s,1H),7.95(d,J＝8.8Hz,2H),7.70(d,J＝8.3Hz,1H),7.17(d,J＝8.7Hz,2H),7.08(d,J＝8.7Hz,1H),2.39(s,3H).HRMS(MALDI)计算值C22H14ClF3N4O3[M+Na]+:497.0599,实测值497.0598.
化合物49：白色粉末，收率95.6％,mp＝217.6-218.3℃.1H NMR(400MHz,DMSO-d6):δ10.39(s,1H),9.05(d,J＝4.8Hz,2H),9.00(s,1H),7.81(d,J＝8.8Hz,2H),7.70(dd,J＝9.8,4.9Hz,1H),7.40–7.28(m,3H),6.97(d,J＝8.8Hz,2H).HRMS(MALDI)计算值C20H12F2N4O3[M+Na]+:417.077,实测值417.0772.
化合物50：白色粉末，收率81.5％,mp＝198.5-199.7℃.1H NMR(400MHz,DMSO-d6):δ10.40(s,1H),9.05(d,J＝4.8Hz,2H),9.01(s,1H),7.84(d,J＝8.9Hz,2H),7.71(t,J＝4.9Hz,1H),7.44–7.35(m,1H),7.27–7.19(m,2H),7.15(dd,J＝10.8,7.2Hz,1H),7.01(d,J＝8.8Hz,2H).HRMS(MALDI)计算值C20H13FN4O3[M+Na]+:399.0864,实测值399.0863.
化合物51：白色粉末，收率81.7％,mp＝173.1-174.2℃.1H NMR(400MHz,DMSO-d6):δ10.45(s,1H),9.05(d,J＝4.9Hz,2H),9.02(s,1H),7.89(d,J＝8.9Hz,2H),7.71(t,J＝4.9Hz,1H),7.30–7.17(m,2H),7.10(d,J＝8.8Hz,2H),6.93(t,J＝7.6Hz,1H).HRMS(MALDI)计算值C20H12F2N4O3[M+Na]+:417.077,实测值417.0774.
化合物52：黄色粉末，收率70.5％,mp＝262.4-263.9℃.1H NMR(400MHz,DMSO-d6):δ10.54(s,1H),9.05(d,J＝5.1Hz,3H),8.26(d,J＝8.6Hz,2H),7.98(d,J＝8.3Hz,2H),7.72(s,1H),7.22(d,J＝8.4Hz,2H),7.14(d,J＝8.6Hz,2H).HRMS(MALDI)计算值C20H13N5O5[M+Na]+:426.0809,实测值426.0806.
化合物53：白色粉末，收率74.7％,mp＝194.3-195.8℃.1H NMR(400MHz,DMSO-d6):δ10.46(s,1H),9.05(d,J＝4.9Hz,2H),9.02(s,1H),7.90(d,J＝8.9Hz,2H),7.71(t,J＝4.9Hz,1H),7.65(dd,J＝8.9,6.0Hz,1H),7.09(dd,J＝16.1,5.9Hz,3H),6.92(dd,J＝9.7,2.8Hz,1H).HRMS(MALDI)计算值C20H12ClFN4O3[M+Na]+:433.0474,实测值433.0472.
化合物54：白色粉末，收率59.6％,mp＝172.3-172.9℃.1H NMR(400MHz,DMSO-d6):δ10.37(s,1H),9.05(d,J＝4.9Hz,2H),9.00(s,1H),7.83(d,J＝8.9Hz,2H),7.71(t,J＝4.9Hz,1H),7.19(d,J＝8.3Hz,2H),7.00(d,J＝18.6Hz,2H),6.91(d,J＝8.4Hz,2H),2.29(s,3H).HRMS(MALDI)计算值C21H16N4O3[M+Na]+:395.1115,实测值395.1119.
化合物55：白色粉末，收率39.6％,mp＝173.5-174.6℃.1H NMR(400MHz,DMSO-d6):δ10.46(s,1H),9.05(d,J＝4.8Hz,2H),9.03(s,1H),7.91(d,J＝8.8Hz,2H),7.72(t,J＝4.8Hz,1H),7.40(t,J＝8.1Hz,1H),7.18(d,J＝7.9Hz,1H),7.11(d,J＝8.8Hz,2H),7.04(s,1H),6.96(d,J＝8.2Hz,1H).HRMS(MALDI)计算值C20H13ClN4O3[M+Na]+:415.0568,实测值415.0571.
化合物56：白色粉末，收率86.8％,mp＝177.3-178.6℃.1H NMR(400MHz,DMSO-d6):δ10.41(s,1H),9.05(d,J＝4.9Hz,2H),9.02(s,1H),7.87(d,J＝8.9Hz,2H),7.71(t,J＝4.9Hz,1H),7.39(t,J＝7.9Hz,2H),7.13(t,J＝7.3Hz,1H),7.02(dd,J＝13.4,8.5Hz,4H).HRMS(MALDI)计算值C20H14N4O3[M+Na]+:381.0958,实测值381.0964.
化合物57：白色粉末，收率31.1％,mp＝174.6-175.2.1H NMR(600MHz,DMSO-d6):δ10.45(s,1H),9.05(s,2H),9.02(s,1H),7.89(d,J＝8.7Hz,2H),7.72(t,J＝4.6Hz,1H),7.43(d,J＝8.6Hz,2H),7.07(d,J＝8.6Hz,2H),7.02(d,J＝8.6Hz,2H).HRMS(MALDI)计算值C20H13ClN4O3[M+Na]+:415.0568,实测值415.0569.
化合物58：白色粉末，收率73.0％,mp＝151.6-152.7℃.1H NMR(400MHz,DMSO-d6):δ10.44(s,1H),9.04(d,J＝4.9Hz,2H),9.01(s,1H),7.89(d,J＝8.8Hz,2H),7.70(t,J＝4.9Hz,1H),7.37(d,J＝8.7Hz,2H),7.09(d,J＝8.8Hz,4H).HRMS(MALDI)计算值C21H13F3N4O4[M+Na]+:465.0781,实测值465.0782.
化合物59：白色粉末，收率54.7％,mp＝92.0-93.1℃.1H NMR(400MHz,DMSO-d6):δ10.46(s,1H),9.04(d,J＝4.6Hz,2H),9.02(s,1H),7.92(d,J＝8.5Hz,2H),7.70(t,J＝4.4Hz,1H),7.49(t,J＝8.2Hz,1H),7.11(t,J＝8.4Hz,3H),7.03–6.92(m,2H).HRMS(MALDI)计算值C21H13F3N4O4[M+Na]+:465.0781,实测值465.0782。
化合物60：1H NMR(400MHz,DMSO-d6)δ9.46(s,1H),8.97(s,1H),8.36(dd,J＝8.1,1.4Hz,1H),7.97–7.83(m,3H),7.63(dt,J＝15.7,8.0Hz,3H),7.34(td,J＝7.4,2.6Hz,2H),7.26(td,J＝7.9,1.5Hz,1H),7.18(dd,J＝8.1,1.1Hz,1H),7.05(d,J＝8.4Hz,1H).HRMS(MALDI)计算值C23H14ClF3N2O3[M+H]+:459.07178,实测值459.07234.
化合物61：1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),8.93(s,1H),8.15(d,J＝7.7Hz,1H),8.01–7.89(m,2H),7.68(d,J＝7.8Hz,1H),7.60(t,J＝7.8Hz,1H),7.51(t,J＝8.6Hz,1H),7.37–7.23(m,2H),7.23–7.10(m,3H),7.06(d,J＝8.9Hz,1H).HRMS(MALDI)计算值C23H14ClF3N2O4[M+H]+:475.06670,实测值475.06838.
化合物62：1H NMR(400MHz,DMSO-d6)δ9.56(s,1H),9.00(s,1H),8.35(dd,J＝7.7,1.9Hz,1H),7.90(d,J＝8.0Hz,2H),7.72–7.53(m,2H),7.32(d,J＝7.9Hz,1H),7.16(tt,J＝9.4,3.9Hz,2H),7.00(d,J＝7.9Hz,1H),6.86(dd,J＝7.8,1.7Hz,1H),6.71(s,1H),3.24(dt,J＝13.8,6.9Hz,1H),2.22(s,3H),1.27(d,J＝6.9Hz,6H).HRMS(MALDI)计算值C26H23ClN2O3[M+H]+:447.14700,实测值447.14832.
化合物63：1H NMR(400MHz,DMSO-d6)δ9.61(s,1H),9.01(s,1H),8.43(dd,J＝7.7,1.6Hz,1H),7.88(d,J＝7.6Hz,2H),7.70–7.55(m,2H),7.35(d,J＝8.0Hz,1H),7.25–7.10(m,2H),6.96(d,J＝7.8Hz,1H),6.91–6.80(m,1H),6.66(s,1H),2.19(s,3H),1.45(s,9H).HRMS(MALDI)计算值C27H25ClN2O3[M+Na]+:483.14459,实测值483.14495.
化合物64：1H NMR(400MHz,DMSO-d6)δ9.63(s,1H),8.93(s,1H),8.12(dd,J＝7.7,1.8Hz,1H),7.97(s,1H),7.93(d,J＝7.8Hz,1H),7.63(dt,J＝25.4,8.2Hz,3H),7.50(d,J＝7.8Hz,1H),7.45(s,1H),7.37–7.24(m,3H),7.15(dd,J＝7.8,1.6Hz,1H).HRMS(MALDI)计算值C23H14ClF3N2O3[M+H]+:459.07178,实测值459.07133.
化合物65：1H NMR(400MHz,DMSO-d6)δ9.70(s,1H),8.92(s,1H),8.03(dd,J＝7.6,1.7Hz,1H),7.99(s,1H),7.95(d,J＝7.7Hz,1H),7.68(d,J＝8.3Hz,1H),7.61(t,J＝7.9Hz,1H),7.45(d,J＝8.3Hz,1H),7.38–7.20(m,5H).HRMS(MALDI)计算值C23H13ClF4N2O3[M+H]+:477.06236,实测值477.06531
化合物66：1H NMR(400MHz,DMSO-d6)δ9.67(s,1H),8.96(s,1H),8.15(d,J＝7.8Hz,1H),8.08(d,J＝8.1Hz,1H),7.98(s,1H),7.93(d,J＝7.5Hz,1H),7.65(dt,J＝15.6,8.4Hz,3H),7.42–7.28(m,3H),7.25(d,J＝7.9Hz,1H).HRMS(MALDI)计算值C24H13ClF6N2O3[M+H]+:527.05917,实测值527.05802.
化合物67：1H NMR(400MHz,DMSO-d6)δ9.59(s,1H),9.01(s,1H),8.43(d,J＝7.7Hz,1H),7.88(d,J＝8.4Hz,2H),7.71–7.55(m,2H),7.45(s,1H),7.28–7.08(m,3H),6.87(d,J＝8.4Hz,1H),6.76(d,J＝8.3Hz,1H),1.49(s,6H),1.29(s,6H).HRMS(MALDI)计算值C30H31ClN2O3[M+H]+:503.20960,实测值503.21136.
化合物68：1H NMR(400MHz,DMSO-d6)δ9.69(s,1H),8.97(s,1H),8.10(d,J＝7.5Hz,1H),8.01(s,1H),7.97(d,J＝7.4Hz,1H),7.65(dt,J＝15.6,7.9Hz,2H),7.48(t,J＝9.7Hz,1H),7.35–7.16(m,4H),7.07(d,J＝7.7Hz,1H).HRMS(MALDI)计算值C22H13Cl2FN2O3[M+H]+:443.03600,实测值443.03826.
化合物69：1H NMR(400MHz,DMSO-d6)δ9.44(s,1H),8.97(s,1H),8.31(d,J＝8.3Hz,2H),8.01(s,1H),7.97(d,J＝7.7Hz,1H),7.74(dd,J＝8.7,1.9Hz,1H),7.65(dt,J＝15.7,8.0Hz,2H),7.36(dd,J＝11.2,4.4Hz,1H),7.32–7.25(m,1H),7.22(d,J＝8.0Hz,1H),6.98(d,J＝8.6Hz,1H).HRMS(MALDI)计算值C23H13ClF3IN2O3[M+H]+:584.96842,实测值584.96752.
化合物70：1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),8.95(s,1H),8.24(d,J＝8.0Hz,1H),8.13(s,1H),8.03(d,J＝8.8Hz,1H),7.96–7.86(m,2H),7.64(dt,J＝15.7,8.0Hz,2H),7.47–7.39(m,1H),7.35(t,J＝3.9Hz,2H),7.20(d,J＝8.8Hz,1H).HRMS(MALDI)计算值C24H13ClF6N2O3[M+H]+:527.05917,实测值527.05774.
化合物71：1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),8.96(s,1H),8.13(dd,J＝7.6,1.9Hz,1H),8.03–7.92(m,2H),7.65(dt,J＝15.6,7.5Hz,2H),7.48(dd,J＝19.5,9.3Hz,1H),7.37–7.20(m,3H),7.07(dd,J＝7.7,1.6Hz,1H),6.99–6.88(m,1H).HRMS(MALDI)计算值C22H13ClF2N2O3[M+H]+:427.06555,实测值427.06442.
化合物72：1H NMR(400MHz,DMSO-d6)δ9.56(s,1H),8.89(s,1H),8.02(d,J＝7.3Hz,1H),7.97–7.86(m,2H),7.66–7.51(m,2H),7.44–7.31(m,2H),7.22–7.11(m,2H),7.09–6.95(m,2H).HRMS(MALDI)计算值C22H13Cl2FN2O3[M+Na]+:465.01795,实测值465.01792.
化合物73：1H NMR(400MHz,DMSO-d6)δ9.60(s,1H),8.94(s,1H),8.10(dd,J＝7.7,1.7Hz,1H),8.01–7.91(m,2H),7.63(ddd,J＝17.6,16.2,8.5Hz,3H),7.34–7.21(m,3H),7.16(dd,J＝7.8,1.4Hz,1H),6.93(dd,J＝8.9,1.9Hz,1H).HRMS(MALDI)计算值C22H13Cl2FN2O3[M+Na]+:465.01795,实测值465.02030.
化合物74：白色粉末,收率87％,mp＝146.2-147.5℃.1H NMR(400MHz,DMSO-d6)δ10.35(s,1H),9.88(s,1H),8.30(s,1H),7.90–7.84(m,2H),7.80–7.74(m,2H),7.50(t,J＝8.3Hz,1H),7.35(dd,J＝8.6,7.3Hz,2H),7.13(dd,J＝9.6,2.8Hz,2H),7.04–6.95(m,3H).HRMS(MALDI)计算值C23H16F3N3O4[M+H]+:456.11657,实测值456.11609.
化合物75：白色粉末，收率83％,mp＝203.8-204.9℃.1H NMR(400MHz,DMSO-d6)δ10.35(s,1H),9.84(s,1H),8.29(s,1H),7.89–7.71(m,4H),7.37(ddd,J＝17.4,8.6,7.3Hz,4H),7.20–7.09(m,1H),7.07–6.96(m,5H).HRMS(MALDI)计算值C22H17N3O3[M+H]+:372.13427,实测值372.13361.
化合物76：1H NMR(400MHz,DMSO-d6)δ9.59(s,1H),8.99(s,1H),8.28–8.19(m,1H),8.01(s,1H),7.96(d,J＝7.5Hz,1H),7.73–7.58(m,3H),7.24(qdd,J＝9.1,8.3,2.2Hz,4H),6.90(d,J＝7.0Hz,1H).HRMS(MALDI)计算值C22H13Cl2FN2O3[M+H]+:443.03600,实测值443.03594.
化合物77：1H NMR(400MHz,DMSO-d6)δ9.62(s,1H),8.98(s,1H),8.22(dd,J＝7.8,1.7Hz,1H),7.99(d,J＝1.8Hz,1H),7.95(d,J＝7.6Hz,1H),7.72–7.59(m,2H),7.50–7.41(m,1H),7.30–7.16(m,5H),6.96(d,J＝7.8Hz,1H).HRMS(MALDI)计算值C22H14ClFN2O3[M+H]+:409.07497,实测值409.07614.
化合物78：1H NMR(400MHz,DMSO-d6)δ9.62(s,1H),8.98(s,1H),8.22(dd,J＝7.7,1.3Hz,1H),7.99(s,1H),7.95(d,J＝7.6Hz,1H),7.72–7.58(m,2H),7.50–7.39(m,1H),7.30–7.13(m,5H),6.96(d,J＝7.8Hz,1H).HRMS(MALDI)计算值C22H14Cl2N2O3[M+Na]+:447.02737,实测值447.02794.
化合物79：1H NMR(400MHz,DMSO-d6)δ9.56(s,1H),8.96(s,1H),8.19(d,J＝7.4Hz,1H),7.94(d,J＝10.1Hz,2H),7.72–7.56(m,2H),7.33–7.10(m,6H),6.98(d,J＝7.6Hz,1H).HRMS(MALDI)计算值C22H14ClFN2O3[M+H]+:409.07497,实测值409.07508.
化合物80：1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),9.01(s,1H),8.35(d,J＝7.9Hz,1H),8.04(s,1H),7.98(d,J＝7.4Hz,1H),7.83(d,J＝8.0Hz,1H),7.67(dt,J＝15.7,8.0Hz,2H),7.43(t,J＝7.8Hz,1H),7.30(t,J＝7.6Hz,1H),7.21(dt,J＝22.3,7.7Hz,2H),7.06(dd,J＝19.7,8.1Hz,2H).HRMS(MALDI)计算值C22H14BrClN2O3[M+H]+:468.99491,实测值468.99770.
化合物81：1H NMR(400MHz,DMSO-d6)δ9.65(s,1H),8.97(s,1H),8.14(dd,J＝7.8,1.6Hz,1H),8.00(d,J＝1.8Hz,1H),7.96(d,J＝7.6Hz,1H),7.71–7.65(m,1H),7.62(t,J＝7.9Hz,1H),7.34–7.17(m,4H),7.11(d,J＝7.9Hz,1H),6.94(t,J＝7.7Hz,1H).HRMS(MALDI)计算值C22H13BrF2N2O3[M+H]+:427.06555,实测值427.06601.
化合物82：1H NMR(400MHz,DMSO-d6)δ9.65(s,1H),8.97(s,1H),8.09(d,J＝7.5Hz,1H),8.05–7.95(m,2H),7.66(dt,J＝15.6,7.9Hz,2H),7.38–7.24(m,2H),7.17(t,J＝6.4Hz,3H).HRMS(MALDI)计算值C22H12ClF3N2O3[M+H]+:445.05613,实测值445.05513.
化合物83：1H NMR(400MHz,DMSO-d6)δ9.53(s,1H),8.99(s,1H),8.28(dd,J＝7.4,2.1Hz,1H),8.00–7.91(m,2H),7.64(dt,J＝15.7,8.0Hz,2H),7.28(d,J＝7.8Hz,1H),7.17(qd,J＝7.5,5.8Hz,2H),7.01(d,J＝7.8Hz,1H),6.82(dd,J＝9.7,7.8Hz,2H).HRMS(MALDI)计算值C26H23ClN2O3[M+H]+:447.14700,实测值447.14634.
化合物84：1H NMR(400MHz,DMSO-d6)δ9.57(s,1H),8.95(d,J＝1.0Hz,1H),8.21(dd,J＝8.0,1.5Hz,1H),8.06(s,1H),8.02–7.89(m,2H),7.75–7.58(m,3H),7.37(dd,J＝11.0,4.5Hz,1H),7.30(dd,J＝11.0,4.4Hz,1H),7.24(d,J＝7.9Hz,1H),7.13(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C23H13Cl2F3N2O3[M+H]+:493.03281,实测值493.03376.
化合物85：1H NMR(400MHz,DMSO-d6)δ9.52(s,1H),8.96(s,1H),8.24(dd,J＝8.0,1.5Hz,1H),8.18(d,J＝1.8Hz,1H),8.00(t,J＝1.7Hz,1H),7.98–7.90(m,1H),7.74(dd,J＝8.7,1.7Hz,1H),7.69(ddd,J＝8.1,2.1,1.2Hz,1H),7.63(t,J＝7.8Hz,1H),7.37(td,J＝7.7,1.6Hz,1H),7.30(td,J＝7.7,1.6Hz,1H),7.24(dd,J＝8.1,1.5Hz,1H),7.09(d,J＝8.5Hz,1H).HRMS(MALDI)计算值C23H13BrClF3N2O3[M+H]+:536.98229,实测值536.98444.
化合物96：1H NMR(400MHz,DMSO-d6)δ10.29(s,1H),8.95(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.89(d,J＝8.8Hz,2H),7.67(dt,J＝15.5,8.2Hz,3H),7.33(d,J＝8.4Hz,1H),7.13(s,1H),7.08(d,J＝8.8Hz,2H).HRMS(MALDI)计算值C22H13Br2ClN2O3[M+H]+:546.90542,实测值546.90522.
化合物97：1H NMR(400MHz,DMSO-d6)δ10.29(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.2Hz,1H),7.90(d,J＝9.0Hz,2H),7.75–7.61(m,3H),7.14(d,J＝8.9Hz,2H),7.09(dd,J＝10.2,2.6Hz,1H),6.80(dd,J＝8.8,2.6Hz,1H).HRMS(MALDI)计算值C22H13BrClFN2O3[M+H]+:420.01537,实测值420.01481.
化合物98：1H NMR(400MHz,DMSO-d6)δ10.27(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.5Hz,1H),7.87(d,J＝9.0Hz,2H),7.75–7.60(m,2H),7.49–7.33(m,2H),7.15–7.00(m,3H).HRMS(MALDI)计算值C22H13BrClFN2O3[M+H]+:486.98549,实测值486.98396.
化合物99：1H NMR(400MHz,DMSO-d6)δ10.27(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.99(d,J＝2.2Hz,1H),7.86(d,J＝9.0Hz,2H),7.72–7.61(m,2H),7.58(dd,J＝8.7,2.3Hz,1H),7.04(d,J＝9.0Hz,2H),6.97(d,J＝8.7Hz,1H).HRMS(MALDI)计算值C22H13Br2ClN2O3[M+Na]+:568.88737,实测值568.88983.
化合物100：1H NMR(400MHz,DMSO-d6)δ10.19(s,1H),8.91(s,1H),8.12(s,1H),8.03(d,J＝6.8Hz,1H),7.85–7.73(m,3H),7.74–7.56(m,3H),7.31(t,J＝7.9Hz,1H),6.81(d,J＝8.5Hz,2H).HRMS(MALDI)计算值C22H13BrCl2N2O3[M+Na]+:524.93788,实测值524.93838.
化合物101：1H NMR(400MHz,DMSO-d6)δ10.16(s,1H),8.91(s,1H),8.12(s,1H),8.03(d,J＝7.4Hz,1H),7.77(d,J＝9.0Hz,2H),7.72–7.59(m,2H),7.13(s,1H),7.02(d,J＝8.1Hz,1H),6.87(d,J＝8.9Hz,2H),6.81(d,J＝8.1Hz,1H).HRMS(MALDI)计算值C24H19ClN2O3[M+H]+:419.11570,实测值419.11676.
化合物102：1H NMR(400MHz,DMSO-d6)δ10.25(s,1H),8.93(s,1H),8.13(s,1H),8.04(d,J＝7.5Hz,1H),7.84(d,J＝9.0Hz,2H),7.75(dd,J＝8.0,1.4Hz,1H),7.67(dt,J＝15.5,4.8Hz,2H),7.46–7.36(m,1H),7.19–7.10(m,1H),7.05(dd,J＝8.2,1.3Hz,1H),7.00(d,J＝9.0Hz,2H).HRMS(MALDI)计算值C22H14ClBrN2O3[M+H]+:468.99491,实测值468.99490.
化合物103：1H NMR(400MHz,DMSO-d6)δ10.25(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.5Hz,1H),7.85(d,J＝9.0Hz,2H),7.73–7.60(m,2H),7.37–7.24(m,2H),7.01(d,J＝9.0Hz,2H),6.96(d,J＝1.4Hz,1H),2.19(s,3H).HRMS(MALDI)计算值C23H16BrClN2O3[M+H]+:483.01506,实测值482.01248.
化合物104：1H NMR(400MHz,DMSO-d6)δ10.29(s,1H),8.95(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.89(t,J＝6.1Hz,2H),7.79(d,J＝7.7Hz,1H),7.67(ddd,J＝15.3,8.1,2.1Hz,3H),7.31(t,J＝7.6Hz,1H),7.10(d,J＝8.9Hz,2H),7.03(d,J＝8.3Hz,1H).HRMS(MALDI)计算值C23H14ClF3N2O3[M+H]+:459.07178,实测值459.07204.
化合物105：1H NMR(400MHz,DMSO-d6)δ10.32(s,1H),8.95(s,1H),8.24(s,1H),8.14(s,1H),8.05(d,J＝7.5Hz,1H),7.92(d,J＝8.9Hz,2H),7.74(d,J＝7.2Hz,1H),7.71–7.60(m,2H),7.14(d,J＝8.9Hz,2H),6.95(d,J＝8.6Hz,1H).
化合物106：1H NMR(400MHz,DMSO-d6)δ10.30(s,1H),8.95(s,1H),8.14(s,1H),8.05(d,J＝7.3Hz,1H),7.91(d,J＝9.0Hz,2H),7.65(dt,J＝18.8,8.2Hz,3H),7.48(d,J＝7.7Hz,1H),7.29(d,J＝6.1Hz,2H),7.15(d,J＝8.9Hz,2H).
化合物107：1H NMR(400MHz,DMSO-d6)δ10.28(s,1H),8.94(s,1H),8.13(s,1H),8.04(d,J＝7.4Hz,1H),7.88(d,J＝9.0Hz,2H),7.79(dd,J＝8.9,6.1Hz,1H),7.73–7.60(m,2H),7.14–7.00(m,3H),6.89(dd,J＝9.9,2.8Hz,1H).HRMS(MALDI)计算值C22H13BrClFN2O3[M+H]+:486.98549,实测值486.98512.
化合物108：1H NMR(400MHz,DMSO-d6)δ10.16(s,1H),8.91(s,1H),8.12(s,1H),8.03(d,J＝7.4Hz,1H),7.74(d,J＝9.0Hz,2H),7.71–7.59(m,2H),7.46(d,J＝7.7Hz,1H),7.36(d,J＝7.4Hz,1H),7.25(t,J＝7.8Hz,1H),6.77(d,J＝9.0Hz,2H),2.15(s,3H).HRMS(MALDI)计算值C23H16Cl2N2O3[M+H]+:439.06107,实测值439.06290.
化合物109：1H NMR(400MHz,DMSO-d6)δ10.21(s,1H),8.92(s,1H),8.12(s,1H),8.03(d,J＝7.4Hz,1H),7.78(d,J＝9.0Hz,2H),7.72–7.59(m,2H),7.56–7.43(m,2H),7.38(td,J＝8.3,5.7Hz,1H),6.91(d,J＝9.0Hz,2H).HRMS(MALDI)计算值C22H13Cl2FN2O3[M+H]+:443.03600,实测值443.03752.
化合物110：1H NMR(400MHz,DMSO-d6)δ10.26(s,1H),8.95(s,1H),8.15(s,1H),8.06(d,J＝7.4Hz,1H),7.86(d,J＝8.8Hz,2H),7.73–7.60(m,3H),6.99(t,J＝7.6Hz,3H),6.90(s,1H),2.27(s,3H).HRMS(MALDI)计算值C23H16BrClN2O3[M+H]+:504.99250,实测值504.99052.
化合物111：1H NMR(400MHz,DMSO-d6)δ10.35(s,1H),8.98(s,1H),8.16(s,1H),8.07(d,J＝7.2Hz,2H),7.96(d,J＝8.8Hz,2H),7.78–7.62(m,3H),7.20(d,J＝8.8Hz,2H),7.11(d,J＝8.7Hz,1H).
化合物112：1H NMR(400MHz,DMSO-d6)δ10.36(s,1H),8.98(s,1H),8.16(s,1H),8.07(d,J＝7.3Hz,1H),7.98(d,J＝8.6Hz,2H),7.87(s,1H),7.70(dd,J＝13.2,7.8Hz,2H),7.64(s,2H),7.27(d,J＝8.7Hz,2H).HRMS(MALDI)计算值C24H13ClF6N2O3[M+H]+:527.05917,实测值527.06108.
化合物113：1H NMR(400MHz,DMSO-d6)δ10.30(s,1H),8.96(s,1H),8.16(s,1H),8.06(d,J＝7.3Hz,1H),7.94–7.83(m,2H),7.69(dt,J＝15.4,7.8Hz,2H),7.25(t,J＝8.6Hz,2H).HRMS(MALDI)计算值C30H31ClN2O3[M+H]+:503.20960,实测值503.21018.
化合物114：1H NMR(400MHz,DMSO-d6)δ10.20(s,1H),8.94(s,1H),8.15(s,1H),8.06(d,J＝7.4Hz,1H),7.80(d,J＝8.3Hz,2H),7.68(dt,J＝15.6,8.0Hz,2H),7.36(s,1H),7.25(d,J＝8.4Hz,1H),6.92(d,J＝8.4Hz,2H),6.85(d,J＝8.5Hz,1H),2.21(s,3H),1.31(s,9H).HRMS(MALDI)计算值C27H25ClN2O3[M+Na]+:483.14459,实测值483.14622.
化合物115：1H NMR(400MHz,DMSO-d6)δ10.21(s,1H),8.94(s,1H),8.15(s,1H),8.06(d,J＝7.4Hz,1H),7.82(d,J＝8.6Hz,2H),7.68(dt,J＝15.6,8.0Hz,2H),7.27(s,1H),7.17(d,J＝8.5Hz,1H),6.95(d,J＝8.7Hz,2H),6.76(d,J＝8.4Hz,1H),1.80(d,J＝7.4Hz,2H),1.62(d,J＝7.4Hz,2H),1.37(s,6H),1.28(s,6H),0.66(t,J＝7.0Hz,6H).
化合物116：1H NMR(400MHz,DMSO-d6)δ10.33(s,1H),8.97(s,1H),8.15(s,1H),8.06(d,J＝7.3Hz,1H),7.94(d,J＝8.7Hz,2H),7.76–7.64(m,2H),7.59(t,J＝9.0Hz,1H),7.20(t,J＝11.3Hz,3H),6.89(d,J＝9.1Hz,1H).
化合物117：1H NMR(400MHz,DMSO-d6)δ10.34(s,1H),8.96(s,1H),8.13(d,J＝1.7Hz,1H),8.05(d,J＝7.4Hz,1H),7.96(d,J＝9.0Hz,2H),7.85(s,1H),7.72–7.63(m,2H),7.62(s,2H).HRMS(MALDI)计算值C24H13ClF6N2O3[M+H]+:527.05917,实测值527.05778.
化合物118：1H NMR(400MHz,DMSO-d6)δ10.23(s,1H),8.93(s,1H),8.13(t,J＝1.6Hz,1H),8.04(dt,J＝7.4,1.5Hz,1H),7.91–7.78(m,2H),7.74–7.60(m,2H),7.30–7.18(m,2H),7.12–6.96(m,4H).HRMS(MALDI)计算值C22H14ClFN2O3[M+H]+:409.07497,实测值409.07517.
化合物119：白色粉末,收率83％,mp＝168.1-169.2℃.1H NMR(400MHz,DMSO-d6)δ10.36(s,1H),9.89(s,1H),8.30(s,1H),7.92–7.81(m,2H),7.81–7.72(m,3H),7.46–7.31(m,3H),7.13(d,J＝9.0Hz,1H),7.12–7.05(m,2H),7.04–6.91(m,1H).HRMS(MALDI)计算值C23H15ClF3N3O4[M+H]+:490.07759,实测值490.07759.
化合物120：白色粉末,收率83％,mp＝189.7-191.6℃.1H NMR(400MHz,DMSO-d6)δ10.57(s,1H),9.93(s,1H),8.33(s,1H),7.94–7.84(m,2H),7.84–7.75(m,2H),7.45–7.34(m,2H),7.31(t,J＝8.4Hz,1H),7.17(dt,J＝8.2,1.2Hz,1H),7.15–7.09(m,1H),7.08–7.02(m,2H),7.02–6.96(m,2H).HRMS(MALDI)计算值C22H16BrN3O3[M+H]+:450.04478,实测值450.04368.
化合物131：1H NMR(400MHz,DMSO-d6)δ10.32(s,1H),8.95(s,1H),8.14(s,1H),8.05(d,J＝7.5Hz,1H),7.80–7.62(m,4H),7.55–7.39(m,2H),7.03(t,J＝8.5Hz,1H),7.00–6.82(m,3H).HRMS(MALDI)计算值C22H14ClFN2O3[M+H]+:409.07497,实测值409.07489.
化合物132：1H NMR(400MHz,DMSO-d6)δ10.22(s,1H),8.91(s,1H),8.11(s,1H),8.02(d,J＝7.5Hz,1H),7.65(dt,J＝15.6,7.8Hz,2H),7.55(d,J＝8.2Hz,1H),7.42(s,1H),7.30(t,J＝8.1Hz,1H),7.15(s,1H),7.05(d,J＝8.1Hz,1H),6.88(d,J＝8.1Hz,1H),6.64(d,J＝8.0Hz,1H),2.29(s,3H),2.13(s,3H).
化合物133：1H NMR(400MHz,DMSO-d6)δ10.24(s,1H),8.92(s,1H),8.12(s,1H),8.03(d,J＝7.1Hz,1H),7.73–7.61(m,2H),7.60(d,J＝8.1Hz,1H),7.53(s,1H),7.33(t,J＝8.2Hz,1H),6.95(d,J＝8.4Hz,1H),6.78(d,J＝1.8Hz,1H),6.73(d,J＝7.4Hz,1H),6.55(dd,J＝8.4,1.8Hz,1H),6.07(s,2H).
化合物134：1H NMR(400MHz,DMSO-d6)δ10.26(s,1H),8.92(s,1H),8.12(s,1H),8.03(d,J＝7.5Hz,1H),7.72–7.59(m,3H),7.55(s,1H),7.35(t,J＝8.2Hz,1H),7.21(t,J＝9.4Hz,1H),7.09(dd,J＝12.2,2.6Hz,1H),6.89(d,J＝8.9Hz,1H),6.76(d,J＝8.1Hz,1H),3.85(s,3H).
化合物135：1H NMR(400MHz,DMSO-d6)δ10.22(s,1H),8.91(s,1H),8.11(t,J＝1.6Hz,1H),8.02(dt,J＝7.4,1.4Hz,1H),7.71–7.60(m,2H),7.60–7.54(m,1H),7.52(t,J＝2.1Hz,1H),7.32(t,J＝8.2Hz,1H),7.09–7.02(m,2H),7.02–6.94(m,2H),6.70(dd,J＝8.2,1.8Hz,1H),3.77(s,3H).
化合物136：1H NMR(400MHz,DMSO-d6)δ10.30(s,1H),8.94(s,1H),8.12(t,J＝1.7Hz,1H),8.03(dt,J＝7.4,1.4Hz,1H),7.78–7.59(m,5H),7.42(t,J＝8.2Hz,1H),7.38(d,J＝2.8Hz,1H),7.07(dd,J＝8.9,2.8Hz,1H),6.93–6.82(m,1H).
化合物137：1H NMR(400MHz,DMSO-d6)δ10.22(s,1H),8.91(s,1H),8.11(t,J＝1.7Hz,1H),8.02(dt,J＝7.4,1.4Hz,1H),7.70–7.60(m,2H),7.60–7.55(m,1H),7.52(t,J＝2.1Hz,1H),7.32(t,J＝8.2Hz,1H),7.06–7.00(m,2H),7.00–6.94(m,2H),6.70(ddd,J＝8.2,2.4,0.8Hz,1H),4.02(q,J＝7.0Hz,2H),1.34(t,J＝7.0Hz,3H).
化合物138：1H NMR(400MHz,DMSO-d6)δ10.27(s,1H),8.92(s,1H),8.12(d,J＝1.7Hz,1H),8.03(d,J＝7.5Hz,1H),7.75–7.54(m,4H),7.37(t,J＝8.2Hz,1H),7.31(t,J＝8.2Hz,1H),6.80(dd,J＝8.0,2.1Hz,1H),6.75(dd,J＝8.2,2.3Hz,1H),6.64(t,J＝2.3Hz,1H),6.60(dd,J＝8.0,2.0Hz,1H),3.75(s,3H).
化合物139：1H NMR(400MHz,DMSO-d6)δ10.25(s,1H),8.92(s,1H),8.11(t,J＝1.6Hz,1H),8.03(dt,J＝7.4,1.4Hz,1H),7.72–7.60(m,3H),7.58(t,J＝2.1Hz,1H),7.35(t,J＝8.2Hz,1H),7.31–7.25(m,2H),7.05–6.94(m,2H),6.82–6.70(m,1H),2.90(dt,J＝13.8,6.9Hz,1H),1.21(d,J＝6.9Hz,6H).
化合物140：1H NMR(400MHz,DMSO-d6)δ10.25(s,1H),8.92(s,1H),8.11(t,J＝1.7Hz,1H),8.03(dt,J＝7.5,1.4Hz,1H),7.71–7.60(m,3H),7.57(t,J＝2.1Hz,1H),7.35(t,J＝8.2Hz,1H),7.23(d,J＝8.6Hz,2H),7.02–6.93(m,2H),6.75(ddd,J＝8.2,2.4,0.8Hz,1H),2.57(dd,J＝16.1,8.3Hz,2H),1.62–1.49(m,2H),1.32(dq,J＝14.5,7.3Hz,2H),0.91(t,J＝7.3Hz,3H).
化合物141：1H NMR(400MHz,DMSO-d6)δ10.28(s,1H),8.93(s,1H),8.12(s,1H),8.03(d,J＝7.4Hz,1H),7.77–7.55(m,4H),7.47(d,J＝8.8Hz,2H),7.39(t,J＝8.1Hz,1H),7.09(d,J＝8.8Hz,2H),6.82(d,J＝6.5Hz,1H).
化合物142：1H NMR(400MHz,DMSO-d6)δ10.30(s,1H),8.92(s,1H),8.85(dd,J＝4.2,1.7Hz,1H),8.32(dd,J＝8.4,1.1Hz,1H),8.09(d,J＝9.2Hz,2H),8.05–7.98(m,1H),7.79–7.71(m,1H),7.70–7.68(m,1H),7.67–7.57(m,3H),7.55–7.50(m,2H),7.44(t,J＝8.2Hz,1H),6.93(ddd,J＝8.2,2.4,0.7Hz,1H).
化合物143：1H NMR(400MHz,DMSO-d6)δ10.23(s,1H),8.91(s,1H),8.11(t,J＝1.7Hz,1H),8.02(dt,J＝7.4,1.4Hz,1H),7.71–7.58(m,3H),7.54(t,J＝2.2Hz,1H),7.33(t,J＝8.2Hz,1H),7.17(d,J＝8.2Hz,1H),6.88(d,J＝2.4Hz,1H),6.79(dd,J＝8.2,2.6Hz,1H),6.73(ddd,J＝8.2,2.4,0.8Hz,1H),2.21(d,J＝1.9Hz,6H).
化合物144：1H NMR(400MHz,DMSO-d6)δ10.23(s,1H),8.92(s,1H),8.11(t,J＝1.6Hz,1H),8.03(dt,J＝7.4,1.4Hz,1H),7.71–7.61(m,2H),7.58(dd,J＝8.2,1.0Hz,1H),7.53(t,J＝2.1Hz,1H),7.33(t,J＝8.2Hz,1H),6.98(d,J＝8.8Hz,1H),6.78(d,J＝2.7Hz,1H),6.76–6.70(m,1H),6.59(dd,J＝8.7,2.7Hz,1H),3.75(d,J＝6.0Hz,6H).
化合物145：1H NMR(400MHz,DMSO-d6)δ10.27(s,1H),8.93(s,1H),8.12(t,J＝1.7Hz,1H),8.03(dt,J＝7.4,1.4Hz,1H),7.71–7.59(m,4H),7.38(t,J＝8.2Hz,1H),6.81(ddd,J＝8.2,2.4,0.8Hz,1H),6.32(t,J＝2.2Hz,1H),6.20(t,J＝3.3Hz,2H),3.73(s,6H).
化合物146：1H NMR(400MHz,DMSO-d6)δ10.24(s,1H),8.92(s,1H),8.12(t,J＝1.7Hz,1H),8.03(dt,J＝7.4,1.4Hz,1H),7.71–7.57(m,3H),7.52(t,J＝2.1Hz,1H),7.33(t,J＝8.2Hz,1H),6.90(d,J＝8.7Hz,1H),6.75–6.70(m,1H),6.61(d,J＝2.8Hz,1H),6.56(dd,J＝8.7,2.8Hz,1H),4.25(q,J＝4.8Hz,4H).
化合物153：白色粉末,收率83％,mp＝168.6-170.0℃.1H NMR(400MHz,DMSO-d6)δ10.58(s,1H),9.99(s,1H),8.35(s,1H),7.92–7.78(m,4H),7.50(t,J＝8.3Hz,1H),7.31(t,J＝8.4Hz,1H),7.22–7.07(m,4H),7.06–6.90(m,2H).HRMS(MALDI)计算值C23H15BrF3N3O4[M+H]+:534.02708,实测值534.02644.
化合物154：白色粉末,收率84％,mp＝183.9-185.0℃.1H NMR(400MHz,DMSO-d6)δ10.54(s,1H),9.86(s,1H),8.31(s,1H),7.86–7.75(m,4H),7.45–7.31(m,4H),7.18–7.09(m,1H),7.09–6.97(m,4H).HRMS(MALDI)计算值C22H16ClN3O3[M+H]+:406.09530,实测值406.09456.
化合物155：白色粉末，收率87％,mp＝189.4-161.0℃.1H NMR(400MHz,DMSO-d6)δ10.58(s,1H),9.99(s,1H),8.35(s,1H),7.92–7.78(m,4H),7.50(t,J＝8.3Hz,1H),7.31(t,J＝8.4Hz,1H),7.22–7.07(m,4H),7.06–6.90(m,2H).HRMS(MALDI)计算值C23H15ClF3N3O4[M+H]+:490.07759,实测值490.07871.
化合物156：白色粉末，收率83％,mp＝179.8-180.6℃.1H NMR(400MHz,DMSO-d6)δ10.74(s,1H),9.97(s,1H),8.35(s,1H),7.99(d,J＝2.6Hz,1H),7.83–7.74(m,3H),7.57(d,J＝8.9Hz,1H),7.39(dd,J＝8.6,7.3Hz,2H),7.18–7.09(m,1H),7.05(d,J＝9.0Hz,2H),7.00(d,J＝7.7Hz,2H).HRMS(MALDI)计算值C22H15Cl2N3O3[M+H]+:440.05632,实测值440.05430.
化合物157：白色粉末，收率80％,mp＝183.1-184.0℃.1H NMR(400MHz,DMSO-d6)δ10.74(s,1H),10.02(s,1H),8.36(s,1H),7.99(d,J＝2.6Hz,1H),7.88–7.82(m,2H),7.77(dd,J＝8.9,2.6Hz,1H),7.57(d,J＝8.8Hz,1H),7.50(t,J＝8.3Hz,1H),7.20–7.06(m,3H),7.04–6.98(m,1H),6.96(t,J＝1.6Hz,1H).HRMS(MALDI)计算值C23H14Cl2F3N3O4[M+H]+:524.03862,实测值524.03829.
化合物158：白色粉末,收率80％,mp＝193.6-194.5℃.1H NMR(400MHz,DMSO-d6)δ10.22(s,1H),9.81(s,1H),8.26(s,1H),7.80(d,J＝9.0Hz,2H),7.63(d,J＝8.5Hz,2H),7.44–7.33(m,2H),7.17–7.09(m,3H),7.02(dd,J＝15.8,8.3Hz,4H),2.27(s,3H).HRMS(MALDI)计算值C23H19N3O3[M+H]+:386.14992,实测值386.14857.
化合物159：白色粉末,收率80％,mp＝156.7-157.8℃.1H NMR(400MHz,DMSO-d6)δ10.23(s,1H),9.86(s,1H),8.28(s,1H),7.92–7.81(m,2H),7.71–7.59(m,2H),7.50(t,J＝8.3Hz,1H),7.12(ddd,J＝10.2,7.8,4.2Hz,5H),7.06–6.94(m,2H).HRMS(MALDI)计算值C24H18F3N3O4[M+H]+:470.13222,实测值470.13161.
化合物218：白色粉末,收率67.3％,mp＝126.6-128.0℃.1H NMR(600MHz,DMSO-d6)δ10.30(s,2H),8.66(s,1H),8.03(s,1H),7.91(d,J＝9.0Hz,2H),7.68(d,J＝8.4Hz,1H),7.14(d,J＝9.0Hz,2H),7.05(d,J＝9.0Hz,2H),2.52(s,3H).HRMS(MALDI)计算值C18H12ClF3N2O3[M+Na]+:419.0381,实测值:419.0386.
化合物219：淡黄色粉末,收率29.2％,mp＝117.7-118.8℃.1H NMR(600MHz,DMSO-d6):δ10.22(s,1H),8.67(s,1H),8.02(s,1H),7.90(d,J＝8.8Hz,2H),7.69(d,J＝8.2Hz,1H),7.14(d,J＝8.8Hz,2H),7.06(d,J＝8.7Hz,1H),2.87(q,J＝7.6Hz,2H),1.30(t,J＝7.6Hz,3H).HRMS(MALDI)计算值C19H14ClF3N2O3[M+Na]+:433.0538,实测值433.0535.
化合物220：白色粉末,收率62.0％,mp＝115.7-116.2℃.1H NMR(600MHz,CDCl3):δ8.74(s,1H),8.19(s,1H),7.73(s,1H),7.71(s,2H),7.42(d,J＝8.5Hz,1H),7.05(d,J＝8.7Hz,2H),6.93(d,J＝8.6Hz,1H),2.78(t,J＝7.4Hz,2H),1.87–1.80(m,2H),1.02(t,J＝7.4Hz,3H).HRMS(MALDI)计算值C20H16ClF3N2O3[M+Na]+:447.0694,实测值447.0693.
化合物221：淡黄色粉末,收率54.0％,mp＝80.1-80.4℃.1H NMR(600MHz,CDCl3):δ8.76(s,1H),8.20(s,1H),7.74(s,1H),7.73(s,2H),7.43(d,J＝8.6Hz,1H),7.06(d,J＝8.9Hz,2H),6.94(d,J＝8.6Hz,1H),3.13(dp,J＝14.1,7.0Hz,1H),1.40(d,J＝7.0Hz,6H).HRMS(MALDI)计算值C20H16ClF3N2O3[M+Na]+:447.0694,实测值447.0716.
化合物222：白色粉末,收率52.9％,mp＝115.4-116.2℃.1H NMR(400MHz,CDCl3-d)δ8.70(s,1H),8.11(s,1H),7.72(d,J＝7.9Hz,3H),7.43(d,J＝8.6Hz,1H),7.04(d,J＝8.0Hz,2H),6.94(d,J＝8.6Hz,1H),2.08(dq,J＝14.3,7.5,7.0Hz,1H),1.12(d,J＝7.9Hz,4H).HRMS(MALDI)计算值C20H14ClF3N2O3[M+Na]+:445.0547,实测值445.0537.
化合物223：白色粉末,收率54.4％,mp＝99.2-100.5℃.1H NMR(600MHz,DMSO-d6):δ10.37(s,1H),8.79(s,1H),8.03(s,1H),7.92(d,J＝8.3Hz,2H),7.69(d,J＝8.4Hz,1H),7.15(d,J＝8.4Hz,2H),7.06(d,J＝8.6Hz,1H),6.75(dd,J＝17.3,11.3Hz,1H),6.29(d,J＝17.6Hz,1H),5.87(d,J＝11.3Hz,1H).HRMS(MALDI)计算值C19H12ClF3N2O3[M+Na]+:431.0381,实测值431.0390.
化合物224：淡黄色粉末,收率16.1％,mp＝146.7-147.8℃.1H NMR(400MHz,CDCl3)δ9.10(s,1H),7.86(s,1H),7.77(s,1H),7.74(d,J＝8.7Hz,2H),7.42(d,J＝8.7Hz,1H),7.05(d,J＝8.7Hz,2H),6.93(d,J＝8.7Hz,1H),3.85–3.81(m,4H),3.66–3.61(m,4H).HRMS(MALDI)计算值C21H17ClF3N3O4[M+Na]+:490.0752,实测值490.0773.
本发明提供的化合物对线粒体呼吸链表现出很强的抑制活性。特别地，本发明提供的化合物对黄瓜霜霉病和黄瓜白粉病均表现出优异的防效，其防效明显高于现有技术的相应防效。
测试例
采用温室盆栽实验对所合成的部分目标化合物进行活体水平的杀菌活性的测定，具体方法参见康卓，顾宝根编写的《农药生物活性测试标准操作规范》杀菌剂卷中SOP-SC-1098黄瓜霜霉病盆栽法和SOP-SC-1101黄瓜白粉病盆栽法。
防效的测试结果列于以下表格中，表格中的A表示防效为80％以上；B表示防效为60-80％(不包括80％)；C表示防效为40-60％(不包括60％)；D表示防效为40％以下(不包括40％)。
表1：第一批目标化合物对黄瓜霜霉病筛选结果
表2：第一批目标化合物对黄瓜白粉病筛选结果
从上述结果可以看出，本发明的化合物对黄瓜霜霉病和黄瓜白粉病表现出良好的防效，特别地，化合物31、32和37在6.25mg/L浓度下对黄瓜霜霉病表现出超过80％的活性，且在该浓度下优于商品化的对照试剂嘧菌酯、噁唑菌酮和吡唑醚菌酯。化合物33、38和39在6.25mg/L浓度下对黄瓜白粉病表现出超过80％的活性，且在该浓度下优于商品化的对照试剂嘧菌酯和噁唑菌酮。
表3：第二批目标化合物对黄瓜霜霉病筛选结果
从上述结果可以看出，本发明的化合物对黄瓜霜霉病和黄瓜白粉病表现出良好的防效，特别地，在低浓度6.25ppm下，化合物69、70、71、72、73、98、100、109等对黄瓜霜霉病活性优于嘧菌酯，噁唑菌酮，吡唑醚菌酯。
表4：第三批目标化合物对黄瓜霜霉病筛选结果
从上述结果可以看出，本发明的化合物对黄瓜霜霉病表现出良好的防效，特别地，在低浓度25ppm和6.25ppm下，化合物142等对黄瓜霜霉病活性优于嘧菌酯，噁唑菌酮，吡唑醚菌酯。
以上详细描述了本发明的优选实施方式，但是，本发明并不限于此。在本发明的技术构思范围内，可以对本发明的技术方案进行多种简单变型，包括各个技术特征以任何其它的合适方式进行组合，这些简单变型和组合同样应当视为本发明所公开的内容，均属于本发明的保护范围。
Claims (11)
1.一种噁唑酰胺类化合物，该化合物具有式(I)所示的结构，
其中，在式(I)中，
R21、R22、R23、R24和R25中的任意一个为式(I1)所示的基团，其余均为H；
R11、R12、R13、R14和R15各自独立地选自H、卤素、由1-3个卤素取代的C1-6的烷基、硝基、C1-6的烷基、由1-3个卤素取代的C1-6的烷氧基、氰基、C1-6的烷氧基，或者R11、R12、R13、R14和R15中的任意相邻两个基团一起形成不含有或者含有选自N和/或O的杂原子的饱和或者不饱和的5-6元环，且R11、R12、R13、R14和R15不全为H；
R31选自C2-4的烷基、C2-4的烯基、取代或未取代的吗啉基、取代或未取代的嘧啶基、取代或未取代的苯基、取代或未取代的吡啶基、取代或未取代的吡嗪基、由苯基取代的C7-12的烷基、由溴苯基取代的C7-12的烷基、由氯苯基取代的C7-12的烷基、由氰基苯基取代的C8-13的烷基、-NHR5，R5选自取代或未取代的苯基；
且该R31和R5中任选含有的取代基各自独立地选自卤素、C2-6的烷基、C1-6的烷氧基、由1-3个卤素取代的C1-6的烷基、苯基、苯氧基、硝基和氰基中的至少一种；
R32选自H、由1-3个卤素取代的C1-3的烷基、C2-3的烷基、C1-3的烷氧基和取代或未取代的苯基；R32中任选存在的取代基各自独立地选自卤素、C1-3的烷氧基中的至少一种；
R4为H、C1-3的烷基、C1-3的烷氧基或C1-3的烷硫基。
2.根据权利要求1所述的化合物，其中，所述噁唑酰胺类化合物选自以下化合物中的至少一种：
化合物1：
化合物2：
化合物3：
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化合物7：
化合物8：
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化合物14：
化合物15：
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化合物19：
化合物20：
化合物21：
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化合物23：
化合物24：
化合物25：
化合物26：
化合物27：
化合物29：
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化合物31：
化合物32：
化合物33：
化合物34：
化合物35：
化合物36：
化合物37：
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化合物41：
化合物42：
化合物43：
化合物44：
化合物45：
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化合物48：
化合物49：
化合物50：
化合物51：
化合物52：
化合物53：
化合物54：
化合物55：
化合物57：
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化合物59：
化合物60：
化合物61：
化合物62：
化合物63：
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化合物67：
化合物68：
化合物69：
化合物70：
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化合物98：
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化合物103：
化合物104：
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化合物106：
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化合物110：
化合物111：
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化合物114：
化合物115：
化合物116：
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化合物122：
化合物123：
化合物124：
化合物125：
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化合物128：
化合物129：
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化合物133：
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化合物140：
化合物141：
化合物142：
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化合物167：
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化合物180：
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化合物186：
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化合物222：
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化合物224：
3.一种制备式(I)所示的噁唑酰胺类化合物的方法，该方法包括：在缩合剂存在下，将式(III)所示的化合物与式(II)所示的化合物进行接触反应，
其中，在式(I)、式(II)和式(III)中的各取代基的定义分别与权利要求1-2中任意一项所述的定义对应相同。
4.根据权利要求3所述的方法，其中，所述缩合剂包括HATU和DIPEA。
5.根据权利要求3所述的方法，其中，所述缩合剂中HATU和DIPEA的用量摩尔比为1：(0.3-1.5)。
6.根据权利要求3所述的方法，其中，所述接触反应的条件包括：温度0-60℃，时间为0.5-48h。
7.权利要求1-2中任意一项所述的噁唑酰胺类化合物在制备杀菌剂中的应用。
8.一种杀菌剂，该杀菌剂中含有活性成分和辅料，所述活性成分包括权利要求1-2中任意一项所述的噁唑酰胺类化合物中的至少一种。
9.根据权利要求8所述的杀菌剂，其中，按所述杀菌剂的总重量计，所述活性成分含量为1-99.9重量％。
10.根据权利要求8所述的杀菌剂，其中，该杀菌剂的剂型选自可湿性粉剂、悬浮剂、水乳剂和水分散粒剂中的至少一种。
11.根据权利要求8-10中任意一项所述的杀菌剂，其中，该杀菌剂中还含有安全剂。
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