CN116003323B - Fluorine-containing pyrazole phenylacetamide derivative and application thereof - Google Patents

Fluorine-containing pyrazole phenylacetamide derivative and application thereof Download PDF

Info

Publication number
CN116003323B
CN116003323B CN202310109208.6A CN202310109208A CN116003323B CN 116003323 B CN116003323 B CN 116003323B CN 202310109208 A CN202310109208 A CN 202310109208A CN 116003323 B CN116003323 B CN 116003323B
Authority
CN
China
Prior art keywords
compound
mhz
nmr
dmso
esi
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202310109208.6A
Other languages
Chinese (zh)
Other versions
CN116003323A (en
Inventor
徐丹
王伟
黄家川
陆正仪
赵思颖
徐功
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Northwest A&F University
Original Assignee
Northwest A&F University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Northwest A&F University filed Critical Northwest A&F University
Priority to CN202310109208.6A priority Critical patent/CN116003323B/en
Publication of CN116003323A publication Critical patent/CN116003323A/en
Application granted granted Critical
Publication of CN116003323B publication Critical patent/CN116003323B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The application relates to a fluorine-containing pyrazole phenylacetamide derivative and application thereof. The compound has broad-spectrum antifungal activity, particularly has obvious inhibition activity on Rhizoctonia solani and Rhizoctonia cerealis, and provides a basis for developing a novel bactericide taking fluorine-containing pyrazole phenylacetamide derivatives as active ingredients.

Description

含氟吡唑苯乙酰胺类衍生物及其应用Fluorine-containing pyrazole phenylacetamide derivatives and their applications

技术领域Technical Field

本发明涉及化学技术以及药物化学技术领域，尤其是一种含氟吡唑苯乙酰胺类衍生物及其应用。The invention relates to the fields of chemical technology and pharmaceutical chemistry technology, in particular to a fluorine-containing pyrazole benzene acetamide derivative and application thereof.

背景技术Background Art

农药是粮食生产过程中重要的生产资料，对于保证农业作物高产稳产具有至关重要的作用。据统计，植物致病真菌感染导致每年全球农作物产量减少20％，且收获后再减少10％，这不仅给农民带来巨大的经济损失，而且严重威胁了全球的粮食生产安全。杀菌剂的应用是目前防治植物致病真菌最有效的措施，每年可挽回大量损失。在众多杀菌剂中，SDHIs类杀菌剂因其高效广谱的抗真菌活性被广泛应用，其作用机制为：通过作用于蛋白复合体Ⅱ影响病原菌的呼吸链电子传递系统，阻碍能量的代谢，抑制病原菌的生长，导致其死亡，从而达到防止病害的目的。Pesticides are important means of production in the grain production process and play a vital role in ensuring high and stable yields of agricultural crops. According to statistics, plant pathogenic fungal infections cause a 20% reduction in global crop yields each year, and another 10% reduction after harvest, which not only brings huge economic losses to farmers, but also seriously threatens global food production security. The use of fungicides is currently the most effective measure to prevent and control plant pathogenic fungi, which can save a lot of losses every year. Among the many fungicides, SDHIs fungicides are widely used because of their high efficiency and broad-spectrum antifungal activity. Their mechanism of action is: by acting on protein complex II to affect the respiratory chain electron transfer system of pathogens, hindering energy metabolism, inhibiting the growth of pathogens, and causing their death, thereby achieving the purpose of preventing diseases.

SDHIs类杀菌剂在化学结构上最为显著的特征是含有酰胺基，新研发的该类杀菌剂是在已有的基础上进行基团替代衍生而成，从1996年到2022年，已有24种SDH抑制剂上市，其中含有吡唑环的占比高达54.17％(13/24)；该类杀菌剂因其广谱和高效抗真菌活性被用于许多作物上的真菌病害，已经成为生产上的一类重要的杀菌剂品种。然而，因其过度及不合理使用，使真菌对该类杀菌剂的耐药性日趋严峻。因此，发现新的靶标或作用机制以开发现行杀菌剂对解决现存问题非常重要。The most notable feature of SDHIs fungicides in chemical structure is that they contain amide groups. The newly developed fungicides are derived from existing ones by replacing groups. From 1996 to 2022, 24 SDH inhibitors have been launched on the market, of which 54.17% (13/24) contain pyrazole rings. This type of fungicide is used to treat fungal diseases on many crops due to its broad-spectrum and high-efficiency antifungal activity, and has become an important fungicide variety in production. However, due to its excessive and unreasonable use, fungal resistance to this type of fungicide has become increasingly severe. Therefore, it is very important to discover new targets or mechanisms of action to develop current fungicides to solve existing problems.

发明内容Summary of the invention

本发明要解决的技术问题是：克服现有技术中之不足，提供一种含氟吡唑苯乙酰胺类衍生物及其应用，本发明的含氟吡唑苯乙酰胺类衍生物具有高效的抑制植物病原菌的化性能。The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art and provide a fluorine-containing pyrazole phenylacetamide derivative and its application. The fluorine-containing pyrazole phenylacetamide derivative of the present invention has the performance of highly effective inhibition of plant pathogens.

本发明解决其技术问题所采用的技术方案是：一种含氟吡唑苯乙酰胺类衍生物，其结构通式如下：The technical solution adopted by the present invention to solve the technical problem is: a fluorine-containing pyrazole benzene acetamide derivative, the general structural formula of which is as follows:

其中，R1为三氟甲基或二氟甲基；R2为甲基、甲氧基、三氟甲基、氟或氯，或将取代苯乙酰基整体替换为2-萘乙酰基；R3为氢、氟或氯。Wherein, R1 is trifluoromethyl or difluoromethyl; R2 is methyl, methoxy, trifluoromethyl, fluorine or chlorine, or the substituted phenylacetyl group is replaced as a whole with 2-naphthylacetyl; R3 is hydrogen, fluorine or chlorine.

一种如上述的含氟吡唑苯乙酰胺类衍生物在抗真菌活性方面的应用。A use of the above-mentioned fluorine-containing pyrazole benzene acetamide derivatives in antifungal activity.

另外，这种含氟吡唑苯乙酰胺类衍生物可以用于制成防治真菌类植物病害的农药制剂。In addition, the fluorine-containing pyrazole benzene acetamide derivative can be used to prepare pesticide preparations for preventing and controlling fungal plant diseases.

本发明的有益效果是：本发明设计合理，具有以下优点：The beneficial effects of the present invention are: the present invention is reasonably designed and has the following advantages:

(1)、本发明中含氟吡唑苯乙酰胺类衍生物以含氟吡唑苯甲酰胺类衍生物为先导化合物，通过延长化合物碳链，将目标分子由“平面”形状转变为“非平面”形状，这就使得目标分子与活性口袋结合具有多种结合模式，从而使目标分子可能与靶标蛋白产生新的结合模式，其结构新颖，以期扩大真菌防治谱、克服日趋严重的耐药性问题；(1) The fluorinated pyrazole benzamide derivatives of the present invention use fluorinated pyrazole benzamide derivatives as lead compounds, and by extending the carbon chain of the compound, the target molecule is transformed from a "planar" shape to a "non-planar" shape, which allows the target molecule to bind to the active pocket in a variety of binding modes, thereby allowing the target molecule to produce a new binding mode with the target protein. The structure is novel, in order to expand the fungal control spectrum and overcome the increasingly serious problem of drug resistance;

(2)、本发明公开了50种含氟吡唑苯乙酰胺类衍生物并提供了这些衍生物的化学结构，同时还验证了其抗菌活性，具体的：采用浓度50mg/L的含氟吡唑苯乙酰胺类衍生物用于油菜菌核病菌、苹果腐烂病菌、小麦全蚀病菌和水稻纹枯病菌4种真菌进行抗菌活性鉴定，结果显示大部分化合物对这4种病菌均有抑制作用。(2) The present invention discloses 50 fluorine-containing pyrazole phenylacetamide derivatives and provides the chemical structures of these derivatives. Meanwhile, their antibacterial activities are verified. Specifically, the fluorine-containing pyrazole phenylacetamide derivatives at a concentration of 50 mg/L are used to identify the antibacterial activities of four fungi, namely, rapeseed sclerotinia, apple rot pathogen, wheat take-all pathogen and rice sheath blight pathogen. The results show that most of the compounds have inhibitory effects on these four pathogens.

具体实施方式DETAILED DESCRIPTION

现在结合优选实施例对本发明作进一步详细的说明。The present invention will now be described in further detail with reference to preferred embodiments.

实施例1化合物1Example 1 Compound 1

化合物1为N-甲基-3-三氟甲基-1H-吡唑-5-基-2-苯基乙酰胺，其化学式如下：Compound 1 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-phenylacetamide, and its chemical formula is as follows:

本实施例中化合物1为黄色固体,产率72％；熔点＝120.0-122.8℃；1H NMR(400MHz,DMSO-d6)δ10.50(s,1H),7.35(d,J＝5.0Hz,4H),7.27(dq,J＝8.7,4.2Hz,1H),6.67(s,1H),3.77(s,3H),3.75(s,2H)；13CNMR(101MHz,DMSO-d6)δ169.8,139.2(q,J＝34.6Hz),135.7,129.7,121.8(q,J＝267.8Hz,97.3,42.5,36.9；ESI-MS calculatedforC13H12F3N3O[M+Na]+,306.0825；found 306.0822.In this example, compound 1 is a yellow solid with a yield of 72%; melting point = 120.0-122.8°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.50 (s, 1H), 7.35 (d, J = 5.0 Hz, 4H), 7.27 (dq, J = 8.7, 4.2 Hz, 1H), 6.67 (s, 1H), 3.77 (s, 3H), 3.75 (s, 2H); 13 CNMR (101 MHz, DMSO-d 6 ) δ 169.8, 139.2 (q, J = 34.6 Hz), 135.7, 129.7, 121.8 (q, J = 267.8 Hz, 97.3, 42.5, 36.9; ESI-MS calculated for C 13 H 12 F 3 N 3 O[M+Na] + ,306.0825; found 306.0822.

实施例2化合物2Example 2 Compound 2

化合物2为N-甲基-3-三氟甲基-1H-吡唑-5-基-2-邻甲苯基乙酰胺，其化学式如下：Compound 2 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-o-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物2为白色固体,产率81％；熔点＝143.3-145.3℃；1H NMR(400MHz,DMSO-d6)δ10.45(s,1H),7.25(s,1H),7.17(t,J＝5.5Hz,3H),6.65(s,1H),3.78(s,5H),2.29(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.7,139.3(q,J＝37.2Hz),138.6,137.2,134.4,130.5,127.4,126.3,125.8,121.8(q,J＝268.1Hz),97.4,36.9,35.2,19.8；ESI-MS calculated for C14H14F3N3O[M+Na]+,320.0981；found 320.0983.In this example, compound 2 is a white solid with a yield of 81%; melting point = 143.3-145.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.45 (s, 1H), 7.25 (s, 1H), 7.17 (t, J = 5.5 Hz, 3H), 6.65 (s, 1H), 3.78 (s, 5H), 2.29 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 169.7, 139.3 (q, J = 37.2 Hz), 138.6, 137.2, 134.4, 130.5, 127.4, 126.3, 125.8, 121.8 (q, J = 268.1 Hz), 97.4, 36.9, 35.2, 19.8; ESI-MS calculated for C 14 H 14 F 3 N 3 O[M+Na] + ,320.0981; found 320.0983.

实施例3化合物3Example 3 Compound 3

化合物3为N-甲基-3-三氟甲基-1H-吡唑-5-基-2-间甲苯基乙酰胺，其化学式如下：Compound 3 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-m-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物3为黄色固体,产率76％；熔点＝114.0-116.0℃；1H NMR(400MHz,DMSO-d6)δ10.44(s,1H),7.22(t,J＝7.5Hz,1H),7.18–7.11(m,2H),7.07(d,J＝7.4Hz,1H),6.65(s,1H),3.76(s,3H),3.70(s,2H),2.30(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.8,139.2(q,J＝37.4Hz),138.6,137.9,135.5,130.3,128.7,127.8,126.7,121.8(q,J＝268.1Hz),97.3,42.4,36.9,21.4；ESI-MS calculated for C14H14F3N3O[M+Na]+,320.0981；found 320.0980.In this example, compound 3 is a yellow solid with a yield of 76%; melting point = 114.0-116.0°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.44 (s, 1H), 7.22 (t, J = 7.5 Hz, 1H), 7.18-7.11 (m, 2H), 7.07 (d, J = 7.4 Hz, 1H), 6.65 (s, 1H), 3.76 (s, 3H), 3.70 (s, 2H), 2.30 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.8,139.2(q,J＝37.4Hz),138.6,137.9,135.5,130.3,128.7,127.8,126.7,121.8(q,J＝268.1Hz),97.3,42.4,36.9,21.4; ESI-MS calculated for C 14 H 14 F 3 N 3 O[M+Na] + ,320.0981; found 320.0980.

实施例4化合物4Example 4 Compound 4

化合物4为N-甲基-3-三氟甲基-1H-吡唑-5-基-2-对甲苯基乙酰胺，其化学式如下：Compound 4 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-p-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物4为黄色固体,产率75％；熔点＝128.8-131.3℃；1H NMR(400MHz,DMSO-d6)δ10.41(s,1H),7.22(d,J＝6.8Hz,2H),7.15(d,J＝7.1Hz,2H),6.64(s,1H),3.75(s,3H),3.68(s,2H),2.29(s,3H)；13C NMR(101MHz,DMSO-d6)δ170.0,138.6,136.2,132.6,129.5,129.4,123.1,97.4,42.1,36.9,21.1；ESI-MS calculated forC14H14F3N3O[M+Na]+,320.0981；found 320.0981.In this example, compound 4 is a yellow solid with a yield of 75%; melting point = 128.8-131.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.41 (s, 1H), 7.22 (d, J = 6.8 Hz, 2H), 7.15 (d, J = 7.1 Hz, 2H), 6.64 (s, 1H), 3.75 (s, 3H), 3.68 (s, 2H), 2.29 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 170.0, 138.6, 136.2, 132.6, 129.5, 129.4, 123.1, 97.4, 42.1, 36.9, 21.1; ESI-MS calculated for C 14 H 14 F 3 N 3 O[M+Na] + ,320.0981; found 320.0981.

实施例5化合物5Example 5 Compound 5

化合物5为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(2-甲氧基苯基)乙酰胺，其化学式如下：Compound 5 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(2-methoxyphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物5为白色固体,产率62％；熔点＝104.0-107.8℃；1H NMR(400MHz,DMSO-d6)δ10.33(s,1H),7.25(q,J＝7.7Hz,2H),6.99(d,J＝8.1Hz,1H),6.91(t,J＝7.4Hz,1H),6.62(s,1H),3.78(s,6H),3.70(s,2H)；13C NMR(101MHz,DMSO-d6)δ169.9,157.7,139.2(d,J＝39.2Hz),138.8,131.5,128.8,124.0,120.7,121.8(q,J＝268.1Hz),111.1,97.5,55.8,37.4,36.8；ESI-MS calculated for C14H14F3N3O2[M+Na]+,336.0930；found 336.0929.In this example, compound 5 is a white solid with a yield of 62%; melting point = 104.0-107.8°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.33 (s, 1H), 7.25 (q, J = 7.7 Hz, 2H), 6.99 (d, J = 8.1 Hz, 1H), 6.91 (t, J = 7.4 Hz, 1H), 6.62 (s, 1H), 3.78 (s, 6H), 3.70 (s, 2H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.9,157.7,139.2(d,J＝39.2Hz),138.8,131.5,128.8,124.0,120.7,121.8(q,J＝268.1Hz),111.1,97.5,55.8,37.4,36.8; ESI-MS calculated for C 14 H 14 F 3 N 3 O 2 [M+Na] + ,336.0930; found 336.0929.

实施例6化合物6Example 6 Compound 6

化合物6为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(3-甲氧基苯基)乙酰胺，其化学式如下：Compound 6 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(3-methoxyphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物6为黄色固体,产率80％；熔点＝108.8-112.5℃；1H NMR(400MHz,DMSO-d6)δ10.44(s,1H),7.25(t,J＝8.0Hz,1H),6.91(d,J＝7.1Hz,2H),6.84(dd,J＝7.3,1.9Hz,1H),6.65(s,1H),3.76(s,3H),3.75(s,3H),3.71(s,2H)；13C NMR(101MHz,DMSO-d6)δ169.6,159.7,139.2(q,J＝37.4Hz),138.6,137.1,129.8,121.8,121.8(q,J＝268.1Hz),115.4,112.6,97.4,55.4,42.5,36.9；ESI-MS calculated for C14H14F3N3O2[M+Na]+,336.0930；found 336.0932.In this example, compound 6 is a yellow solid with a yield of 80%; melting point = 108.8-112.5°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.44 (s, 1H), 7.25 (t, J = 8.0 Hz, 1H), 6.91 (d, J = 7.1 Hz, 2H), 6.84 (dd, J = 7.3, 1.9 Hz, 1H), 6.65 (s, 1H), 3.76 (s, 3H), 3.75 (s, 3H), 3.71 (s, 2H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.6,159.7,139.2(q,J＝37.4Hz),138.6,137.1,129.8,121.8,121.8(q,J＝268.1Hz),115.4,112.6,97.4,55.4,42.5,36.9; ESI-MS calculated for C 14 H 14 F 3 N 3 O 2 [M+Na] + ,336.0930; found 336.0932.

实施例7化合物7Example 7 Compound 7

化合物7为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(4-甲氧基苯基)乙酰胺，其化学式如下：Compound 7 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(4-methoxyphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物7为黄色固体,产率69％；熔点＝119.2-121.0℃；1H NMR(400MHz,Chloroform-d)δ7.26(s,1H),7.23(s,1H),7.10(s,1H),6.95(d,J＝8.5Hz,2H),6.47(s,1H),3.83(s,3H),3.71(s,2H),3.61(s,3H)；13C NMR(101MHz,Chloroform-d)δ169.8,159.4,140.9(q,J＝38.6Hz),136.0,130.6,125.3,120.9(q,J＝268.5Hz),114.9,98.6,55.4,42.8,36.1；ESI-MS calculated for C14H14F3N3O2[M+Na]+,336.0930；found336.0931.In this example, compound 7 is a yellow solid with a yield of 69%; melting point = 119.2-121.0°C; 1 H NMR (400 MHz, Chloroform-d) δ 7.26 (s, 1H), 7.23 (s, 1H), 7.10 (s, 1H), 6.95 (d, J = 8.5 Hz, 2H), 6.47 (s, 1H), 3.83 (s, 3H), 3.71 (s, 2H), 3.61 (s, 3H); 13 C NMR (101MHz, Chloroform-d) δ169.8,159.4,140.9(q,J＝38.6Hz),136.0,130.6,125.3,120.9(q,J＝268.5Hz),114.9,98.6,55.4,42.8,36.1; ESI-MS calculated for C 14 H 14 F 3 N 3 O 2 [M+Na] + ,336.0930; found336.0931.

实施例8化合物8Example 8 Compound 8

化合物8为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(2-氟苯基)乙酰胺，其化学式如下：Compound 8 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(2-fluorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物8为白色固体,产率88％；熔点＝153.7-155.8℃；1H NMR(400MHz,DMSO-d6)δ10.53(s,1H),7.37(dt,J＝29.3,6.8Hz,2H),7.19(q,J＝7.2Hz,2H),6.65(s,1H),3.83(s,2H),3.79(s,3H)；13CNMR(101MHz,DMSO-d6)δ168.8,162.4,159.9,139.3(q,J＝37.2Hz),138.5,132.5,132.5,129.5,129.4,124.7,123.1,122.8,121.8(q,J＝268.1Hz),115.6,115.4,36.9,35.8；ESI-MS calculated for C13H11F4N4O[M+Na]+,324.0731；found 324.0728.In this example, compound 8 is a white solid with a yield of 88%; melting point = 153.7-155.8°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.53 (s, 1H), 7.37 (dt, J = 29.3, 6.8 Hz, 2H), 7.19 (q, J = 7.2 Hz, 2H), 6.65 (s, 1H), 3.83 (s, 2H), 3.79 (s, 3H); 13 CNMR (101 MHz, DMSO-d 6 )δ168.8,162.4,159.9,139.3(q,J＝37.2Hz),138.5,132.5,132.5,129.5,129.4,124.7,123.1,122.8,121.8(q,J＝268.1Hz),115.6,115.4,36.9,35 .8; ESI-MS calculated for C 13 H 11 F 4 N 4 O[M+Na] + ,324.0731; found 324.0728.

实施例9化合物9Example 9 Compound 9

化合物9为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(3-氟苯基)乙酰胺，其化学式如下：Compound 9 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(3-fluorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物9为黄色固体,产率76％；熔点＝131.6-133.8℃；1H NMR(400MHz,DMSO-d6)δ10.50(s,1H),7.39(q,J＝8.0Hz,1H),7.18(d,J＝7.8Hz,2H),7.11(t,J＝8.8Hz,1H),6.66(s,1H),3.79(d,J＝7.4Hz,5H)；13C NMR(101MHz,DMSO-d6)δ169.3,162.5(d,J＝243.1Hz),139.3(q,J＝35.7Hz),138.4,138.3,130.6(d,J＝8.5Hz),125.9,121.8(q,J＝804.1Hz),116.6(d,J＝21.5Hz),114.0(d,J＝20.9Hz),97.4,41.9,36.9；ESI-MScalculated for C13H11F4N4O[M+Na]+,324.0731；found 324.0728.In this example, compound 9 is a yellow solid with a yield of 76%; melting point = 131.6-133.8°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.50 (s, 1H), 7.39 (q, J = 8.0 Hz, 1H), 7.18 (d, J = 7.8 Hz, 2H), 7.11 (t, J = 8.8 Hz, 1H), 6.66 (s, 1H), 3.79 (d, J = 7.4 Hz, 5H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.3,162.5(d,J＝243.1Hz),139.3(q,J＝35.7Hz),138.4,138.3,130.6(d,J＝8.5Hz),125.9,121.8(q,J＝804.1Hz),116.6(d,J＝21.5Hz),114.0(d,J＝ 20.9Hz),97.4,41.9,36.9; ESI-MScalculated for C 13 H 11 F 4 N 4 O[M+Na] + ,324.0731; found 324.0728.

实施例10化合物10Example 10 Compound 10

化合物10为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(4-氟苯基)乙酰胺，其化学式如下：Compound 10 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(4-fluorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物10为黄色固体,产率74％；熔点＝132.6-134.5℃；1H NMR(400MHz,DMSO-d6)δ10.46(s,1H),7.38(dd,J＝8.3,5.8Hz,2H),7.17(t,J＝8.9Hz,2H),6.65(s,1H),3.76(d,J＝6.6Hz,5H)；13CNMR(101MHz,DMSO-d6)δ169.7,161.7(d,J＝242.4Hz),139.2(q,J＝36.9Hz),138.5,131.8(d,J＝3.0Hz),131.6(d,J＝8.1Hz),125.8,121.8(q,J＝268.1Hz),115.5(d,J＝21.2Hz),97.3,41.5,36.9；ESI-MS calculated forC13H11F4N4O[M+Na]+,324.0731；found 324.0725.In this example, compound 10 is a yellow solid with a yield of 74%; melting point = 132.6-134.5°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.46 (s, 1H), 7.38 (dd, J = 8.3, 5.8 Hz, 2H), 7.17 (t, J = 8.9 Hz, 2H), 6.65 (s, 1H), 3.76 (d, J = 6.6 Hz, 5H); 13 CNMR (101 MHz, DMSO-d 6 )δ169.7,161.7(d,J＝242.4Hz),139.2(q,J＝36.9Hz),138.5,131.8(d,J＝3.0Hz),131.6(d,J＝8.1Hz),125.8,121.8(q,J＝268.1Hz),115.5(d,J＝21.2Hz), 97.3,41.5,36.9; ESI-MS calculated forC 13 H 11 F 4 N 4 O[M+Na] + ,324.0731; found 324.0725.

实施例11化合物11Example 11 Compound 11

化合物11为2-(2-氯苯基)-N-(3-三氟甲基)-1-甲基-1H-吡唑-5-基乙酰胺，其化学式如下：Compound 11 is 2-(2-chlorophenyl)-N-(3-trifluoromethyl)-1-methyl-1H-pyrazol-5-yl acetamide, and its chemical formula is as follows:

本实施例中化合物11为黄色固体,产率86％；熔点＝163.5-165.1℃；1H NMR(400MHz,Chloroform-d)δ7.45(dt,J＝24.6,4.5Hz,2H),7.38–7.31(m,2H),7.13(s,1H),6.47(s,1H),3.90(s,2H),3.70(s,3H)；13C NMR(101MHz,Chloroform-d)δ168.1,135.8,134.2,134.0,131.9,131.8,130.2,129.9,127.9,122.2,99.1,41.6,36.3；ESI-MScalculated for C13H11ClF3N3O[M+Na]+,340.0435；found 340.0435.In this example, compound 11 is a yellow solid with a yield of 86%; melting point = 163.5-165.1°C; 1 H NMR (400 MHz, Chloroform-d) δ7.45 (dt, J = 24.6, 4.5 Hz, 2H), 7.38-7.31 (m, 2H), 7.13 (s, 1H), 6.47 (s, 1H), 3.90 (s, 2H), 3.70 (s, 3H); 13 C NMR (101 MHz, Chloroform-d) δ168.1, 135.8, 134.2, 134.0, 131.9, 131.8, 130.2, 129.9, 127.9, 122.2, 99.1, 41.6, 36.3; ESI-MS calculated for C 13 H 11 ClF 3 N 3 O[M+Na] + ,340.0435; found 340.0435.

实施例12化合物12Example 12 Compound 12

化合物12为2-(3-氯苯基)-N-(3-三氟甲基)-1-甲基吡唑-5-乙酰胺，其化学式如下：Compound 12 is 2-(3-chlorophenyl)-N-(3-trifluoromethyl)-1-methylpyrazole-5-acetamide, and its chemical formula is as follows:

本实施例中化合物12为白色固体,产率82％；熔点＝127.1-130.9℃；1H NMR(400MHz,DMSO-d6)δ10.48(s,1H),7.42–7.34(m,4H),6.65(s,1H),3.77(s,5H)；13C NMR(101MHz,DMSO-d6)δ169.3,139.2(q,J＝38.1,37.7Hz),138.5,138.0,133.3,130.6,129.7,128.5,127.2,121.8(q,J＝268.3Hz),97.3,41.8,36.9；ESI-MS calculated forC13H11ClF3N3O[M+Na]+,340.0435；found 340.0435.In this example, compound 12 is a white solid with a yield of 82%; melting point = 127.1-130.9°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.48 (s, 1H), 7.42–7.34 (m, 4H), 6.65 (s, 1H), 3.77 (s, 5H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 169.3, 139.2 (q, J = 38.1, 37.7 Hz), 138.5, 138.0, 133.3, 130.6, 129.7, 128.5, 127.2, 121.8 (q, J = 268.3 Hz), 97.3, 41.8, 36.9; ESI-MS calculated for C 13 H 11 ClF 3 N 3 O[M+Na] + ,340.0435; found 340.0435.

实施例13化合物13Example 13 Compound 13

化合物13为2-(4-氯苯基)-N-(3-三氟甲基)-1-甲基-1H-吡唑-5-基乙酰胺，其化学式如下：Compound 13 is 2-(4-chlorophenyl)-N-(3-trifluoromethyl)-1-methyl-1H-pyrazol-5-yl acetamide, and its chemical formula is as follows:

本实施例中化合物13为黄色固体,产率83％；熔点＝157.3-159.1℃；1H NMR(400MHz,DMSO-d6)δ10.5(s,1H),7.4(q,J＝8.5Hz,4H),6.7(s,1H),3.8(s,5H)；13C NMR(101MHz,DMSO-d6)δ169.4,139.2(q,J＝38.3,37.5Hz),138.5,134.6,131.9,131.6,128.7,121.8(q,J＝268.1Hz),97.4,41.6,36.9；ESI-MS calculated for C13H11ClF3N3O[M+Na]+,340.0435；found 340.0434.In this example, compound 13 is a yellow solid with a yield of 83%; melting point = 157.3-159.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.5 (s, 1H), 7.4 (q, J = 8.5 Hz, 4H), 6.7 (s, 1H), 3.8 (s, 5H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 169.4, 139.2 (q, J = 38.3, 37.5 Hz), 138.5, 134.6, 131.9, 131.6, 128.7, 121.8 (q, J = 268.1 Hz), 97.4, 41.6, 36.9; ESI-MS calculated for C 13 H 11 ClF 3 N 3 O[M+Na] + , 340.0435; found 340.0434.

实施例14化合物14Example 14 Compound 14

化合物14为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(2-三氟甲基苯基)乙酰胺，其化学式如下：Compound 14 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(2-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物14为黄色固体,产率77％；熔点＝173.3-174.9℃；1H NMR(400MHz,DMSO-d6)δ10.5(s,1H),7.7(d,J＝7.8Hz,1H),7.7(t,J＝7.5Hz,1H),7.5(dd,J＝18.2,7.9Hz,2H),6.6(s,1H),4.0(s,2H),3.8(s,3H)；13C NMR(101MHz,DMSO-d6)δ168.9,139.3(q,J＝37.4Hz),138.5,134.0,133.6,133.6,132.8,128.0(q,J＝29.3Hz),126.2(q,J＝5.5Hz),126.1,126.1,125.8,123.3(d,J＝48.4Hz),120.4,97.4,36.9；ESI-MScalculated for C14H11F6N3O[M+Na]+,374.0699；found 374.0697.In this example, compound 14 is a yellow solid with a yield of 77%; melting point = 173.3-174.9°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.5 (s, 1H), 7.7 (d, J = 7.8 Hz, 1H), 7.7 (t, J = 7.5 Hz, 1H), 7.5 (dd, J = 18.2, 7.9 Hz, 2H), 6.6 (s, 1H), 4.0 (s, 2H), 3.8 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ168.9,139.3(q,J＝37.4Hz),138.5,134.0,133.6,133.6,132.8,128.0(q,J＝29.3Hz),126.2(q,J＝5.5Hz),126.1,126.1,125.8,123.3(d,J＝48.4Hz), 120.4,97.4,36.9; ESI-MScalculated for C 14 H 11 F 6 N 3 O[M+Na] + ,374.0699; found 374.0697.

实施例15化合物15Example 15 Compound 15

化合物15为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(3-三氟甲基苯基)乙酰胺，其化学式如下：Compound 15 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(3-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物15为白色固体,产率75％；熔点＝166.8-170.1℃；1H NMR(400MHz,DMSO-d6)δ10.56(s,1H),7.72(s,1H),7.65(d,J＝7.6Hz,2H),7.62–7.56(m,1H),6.67(s,1H),3.91(s,2H),3.79(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.2,δ139.2(q,J＝37.6Hz),138.5,137.0,134.0,129.8,129.5(q,J＝30.9Hz),126.5(q,J＝4.1Hz),126.1,124.0,123.2(q,J＝25.7Hz),120.4,97.3,41.8,36.9；ESI-MS calculated for C14H11F6N3O[M+Na]+,374.0699；found 374.0697.In this example, compound 15 is a white solid with a yield of 75%; melting point = 166.8-170.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.56 (s, 1H), 7.72 (s, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.62-7.56 (m, 1H), 6.67 (s, 1H), 3.91 (s, 2H), 3.79 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.2,δ139.2(q,J＝37.6Hz),138.5,137.0,134.0,129.8,129.5(q,J＝30.9Hz),126.5(q,J＝4.1Hz),126.1,124.0,123.2(q,J＝25.7Hz),120.4,97.3 ,41.8,36.9; ESI-MS calculated for C 14 H 11 F 6 N 3 O[M+Na] + ,374.0699; found 374.0697.

实施例16化合物16Example 16 Compound 16

化合物16为N-(3-三氟甲基)-1-甲基吡唑-5-基-2-(4-三氟甲基苯基)乙酰胺，其化学式如下：Compound 16 is N-(3-trifluoromethyl)-1-methylpyrazol-5-yl-2-(4-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物16为黄色固体,产率71％；熔点＝138.1-141.1℃；1H NMR(400MHz,DMSO-d6)δ10.55(s,1H),7.71(d,J＝7.2Hz,2H),7.57(d,J＝7.2Hz,2H),6.66(s,1H),3.89(s,2H),3.78(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.2,139.3(q,J＝37.7Hz),138.5,137.0,134.0,129.8,129.5(q,J＝31.2Hz),126.5(q,J＝3.7Hz),126.1,124.0,123.2(q,J＝25.7Hz),97.3,41.8,36.9；ESI-MS calculated for C14H11F6N3O[M+Na]+,374.0699；found 374.0697.In this example, compound 16 is a yellow solid with a yield of 71%; melting point = 138.1-141.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.55 (s, 1H), 7.71 (d, J = 7.2 Hz, 2H), 7.57 (d, J = 7.2 Hz, 2H), 6.66 (s, 1H), 3.89 (s, 2H), 3.78 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.2,139.3(q,J＝37.7Hz),138.5,137.0,134.0,129.8,129.5(q,J＝31.2Hz),126.5(q,J＝3.7Hz),126.1,124.0,123.2(q,J＝25.7Hz),97.3,41.8,3 6.9; ESI-MS calculated for C 14 H 11 F 6 N 3 O[M+Na] + ,374.0699; found 374.0697.

实施例17化合物17Example 17 Compound 17

化合物17为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-苯基乙酰胺，其化学式如下：Compound 17 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-phenylacetamide, and its chemical formula is as follows:

本实施例中化合物17为黄色固体,产率82％；熔点＝92.6-93.0℃；1H NMR(400MHz,DMSO-d6)δ10.31(s,1H),7.29(d,J＝5.0Hz,4H),7.24–7.18(m,1H),6.42(s,1H),3.68(s,2H),3.65(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.7,144.3(t,J＝28.6Hz),138.1,135.8,129.6,128.8,127.2,112.0(t,J＝231.5Hz),96.5,42.5,36.5；ESI-MS calculatedfor C13H13F2N3O[M+Na]+,288.0919；found 288.0920.In this example, compound 17 is a yellow solid with a yield of 82%; melting point = 92.6-93.0°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.31 (s, 1H), 7.29 (d, J = 5.0 Hz, 4H), 7.24-7.18 (m, 1H), 6.42 (s, 1H), 3.68 (s, 2H), 3.65 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 169.7, 144.3 (t, J = 28.6 Hz), 138.1, 135.8, 129.6, 128.8, 127.2, 112.0 (t, J = 231.5 Hz), 96.5, 42.5, 36.5; ESI-MS calculated for C 13 H 13 F 2 N 3 O[M+Na] + ,288.0919; found 288.0920.

实施例18化合物18Example 18 Compound 18

化合物18为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-邻甲苯基乙酰胺，其化学式如下：Compound 18 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-o-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物18为黄色固体,产率85％；熔点＝164.5-165.9℃；1H NMR(400MHz,DMSO-d6)δ10.35(s,1H),7.29–7.22(m,1H),7.22–7.12(m,3H),6.48(s,1H),3.77(s,2H),3.73(s,3H),2.30(s,3H)；13CNMR(101MHz,DMSO-d6)δ169.7,144.30(t,J＝28.4Hz),138.2,137.2,134.5,130.5,127.3,126.3,112.01(t,J＝231.6Hz),96.5,36.5,19.8；ESI-MS calculated for C14H15F2N3O[M+Na]+,302.1075；found 302.1070.In this example, compound 18 is a yellow solid with a yield of 85%; melting point = 164.5-165.9°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.35 (s, 1H), 7.29-7.22 (m, 1H), 7.22-7.12 (m, 3H), 6.48 (s, 1H), 3.77 (s, 2H), 3.73 (s, 3H), 2.30 (s, 3H); 13 CNMR (101 MHz, DMSO-d 6 )δ169.7,144.30(t,J＝28.4Hz),138.2,137.2,134.5,130.5,127.3,126.3,112.01(t,J＝231.6Hz),96.5,36.5,19.8; ESI-MS calculated for C 14 H 15 F 2 N 3 O[M+Na] + ,302.1075; found 302.1070.

实施例19化合物19Example 19 Compound 19

化合物19为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-间甲苯基乙酰胺，其化学式如下：Compound 19 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-m-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物19为白色固体,产率66％；熔点＝122.5-124.6℃；1H NMR(400MHz,Chloroform-d)δ7.32(t,J＝7.5Hz,1H),7.21–7.11(m,3H),6.94(s,1H),6.40(s,1H),3.74(s,2H),3.59(s,3H),2.39(s,3H)；13C NMR(101MHz,Chloroform-d)δ169.5,145.2(t,J＝29.4Hz),139.4,135.9,133.6,130.2,129.4,128.9,126.4,111.1(t,J＝234.2Hz),97.8,43.7,35.8,21.4；ESI-MS calculated for C14H15F2N3O[M+Na]+,302.1075；found302.1069.In this example, compound 19 is a white solid with a yield of 66%; melting point = 122.5-124.6°C; 1 H NMR (400 MHz, Chloroform-d) δ 7.32 (t, J = 7.5 Hz, 1H), 7.21-7.11 (m, 3H), 6.94 (s, 1H), 6.40 (s, 1H), 3.74 (s, 2H), 3.59 (s, 3H), 2.39 (s, 3H); 13 C NMR (101MHz, Chloroform-d) δ 169.5, 145.2 (t, J = 29.4Hz), 139.4, 135.9, 133.6, 130.2, 129.4, 128.9, 126.4, 111.1 (t, J = 234.2Hz), 97.8, 43.7, 35.8, 21.4; ESI-MS calculated for C 14 H 15 F 2 N 3 O[M+Na] + ,302.1075; found302.1069.

实施例20化合物20Example 20 Compound 20

化合物20为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-对甲苯基乙酰胺，其化学式如下：Compound 20 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-p-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物20为黄色固体,产率71％；熔点＝160.1-162.0℃；1H NMR(400MHz,DMSO-d6)δ10.35(s,1H),7.26(d,J＝6.5Hz,2H),7.18(d,J＝6.7Hz,2H),6.49(s,1H),3.72(d,J＝10.3Hz,5H),2.32(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.9,144.3(t,J＝28.5Hz),138.2,136.2,132.7,129.4,112.0(t,J＝231.5Hz),96.5,42.1,36.5,21.1；ESI-MS calculated for C14H15F2N3O[M+Na]+,302.1075；found 302.1072.In this example, compound 20 is a yellow solid with a yield of 71%; melting point = 160.1-162.0°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.35 (s, 1H), 7.26 (d, J = 6.5 Hz, 2H), 7.18 (d, J = 6.7 Hz, 2H), 6.49 (s, 1H), 3.72 (d, J = 10.3 Hz, 5H), 2.32 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 169.9, 144.3 (t, J = 28.5 Hz), 138.2, 136.2, 132.7, 129.4, 112.0 (t, J = 231.5 Hz), 96.5, 42.1, 36.5, 21.1; ESI-MS calculated for C 14 H 15 F 2 N 3 O[M+Na] + ,302.1075; found 302.1072.

实施例21化合物21Example 21 Compound 21

化合物21为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(2-甲氧基苯基)乙酰胺，其化学式如下：Compound 21 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(2-methoxyphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物21为黄色固体,产率87％；熔点＝103.5-105.3℃；1H NMR(400MHz,DMSO-d6)δ10.17(s,1H),7.19(q,J＝7.8Hz,2H),6.93(d,J＝8.1Hz,1H),6.85(d,J＝14.8Hz,1H),6.38(s,1H),3.72(s,3H),3.67(s,3H),3.63(s,2H)；13C NMR(101MHz,DMSO-d6)δ169.9,157.7,144.3(t,J＝28.9Hz),138.3,131.5,128.7,124.1,120.6,112.0(t,J＝231.5Hz),111.1,96.6,55.8,37.4,36.5；ESI-MS calculated for C14H15F2N3O2[M+Na]+,318.1025；found 318.1023.In this example, compound 21 is a yellow solid with a yield of 87%; melting point = 103.5-105.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.17 (s, 1H), 7.19 (q, J = 7.8 Hz, 2H), 6.93 (d, J = 8.1 Hz, 1H), 6.85 (d, J = 14.8 Hz, 1H), 6.38 (s, 1H), 3.72 (s, 3H), 3.67 (s, 3H), 3.63 (s, 2H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.9,157.7,144.3(t,J＝28.9Hz),138.3,131.5,128.7,124.1,120.6,112.0(t,J＝231.5Hz),111.1,96.6,55.8,37.4,36.5; ESI-MS calculated for C 14 H 15 F 2 N 3 O 2 [M+Na] + ,318.1025; found 318.1023.

实施例22化合物22Example 22 Compound 22

化合物22为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(3-甲氧基苯基)乙酰胺，其化学式如下：Compound 22 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(3-methoxyphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物22为白色固体,产率65％；熔点＝100.1-103.2℃；1H NMR(400MHz,DMSO-d6)δ10.32(s,1H),7.25(t,J＝8.0Hz,1H),6.92(s,2H),6.90–6.82(m,2H),6.45(s,1H),3.75(s,3H),3.70(d,J＝3.3Hz,5H)；13C NMR(101MHz,DMSO-d6)δ169.6,159.7,144.3(t,J＝28.4Hz),138.1,137.2,129.8,121.8,115.4,112.6,112.0(t,J＝231.6Hz),96.6,55.4,42.6,36.5；ESI-MS calculated for C14H15F2N3O2[M+Na]+,318.1025；found318.1022.In this example, compound 22 is a white solid with a yield of 65%; melting point = 100.1-103.2°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.32 (s, 1H), 7.25 (t, J = 8.0 Hz, 1H), 6.92 (s, 2H), 6.90-6.82 (m, 2H), 6.45 (s, 1H), 3.75 (s, 3H), 3.70 (d, J = 3.3 Hz, 5H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.6,159.7,144.3(t,J＝28.4Hz),138.1,137.2,129.8,121.8,115.4,112.6,112.0(t,J＝231.6Hz),96.6,55.4,42.6,36.5; ESI-MS calculated for C 14 H 15 F 2 N 3 O 2 [M+Na] + ,318.1025; found318.1022.

实施例23化合物23Example 23 Compound 23

化合物23为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(4-甲氧基苯基)乙酰胺，其化学式如下：Compound 23 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(4-methoxyphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物23为黄色固体,产率75％；熔点＝99.9-102.4℃；1H NMR(400MHz,DMSO-d6)δ10.31(s,1H),7.26(d,J＝8.5Hz,2H),6.91(d,J＝8.5Hz,2H),3.74(s,3H),3.70(s,3H),3.65(s,2H)；13C NMR(101MHz,DMSO-d6)δ170.1,158.6,144.3(t,J＝28.7Hz),138.2,130.6,127.7,114.3,112.0(t,J＝231.5Hz),96.5,55.5,41.6,36.5；ESI-MS calculated for C14H15F2N3O2[M+Na]+,318.1025；found 318.1022.In this example, compound 23 is a yellow solid with a yield of 75%; melting point = 99.9-102.4°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.31 (s, 1H), 7.26 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 8.5 Hz, 2H), 3.74 (s, 3H), 3.70 (s, 3H), 3.65 (s, 2H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 170.1, 158.6, 144.3 (t, J = 28.7 Hz), 138.2, 130.6, 127.7, 114.3, 112.0 (t, J = 231.5 Hz), 96.5, 55.5, 41.6, 36.5; ESI-MS calculated for C 14 H 15 F 2 N 3 O 2 [M+Na] + ,318.1025; found 318.1022.

实施例24化合物24Example 24 Compound 24

化合物24为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(2-氟苯基)乙酰胺，其化学式如下：Compound 24 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(2-fluorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物24为黄色固体,产率82％；熔点＝119.5-122.5℃；1H NMR(400MHz,DMSO-d6)δ10.40(s,1H),7.40(t,J＝7.6Hz,1H),7.33(q,J＝6.6,5.7Hz,1H),7.19(q,J＝7.2Hz,2H),6.45(s,1H),3.82(s,2H),3.73(s,3H)；13C NMR(101MHz,DMSO-d6)δ168.8,161.1(d,J＝244.3Hz),144.3(t,J＝28.4Hz),138.1,132.5(d,J＝4.4Hz),129.5(d,J＝8.1Hz),124.7(d,J＝3.4Hz),122.9(d,J＝15.9Hz),115.5(d,J＝21.5Hz),112.0(t,J＝231.6Hz),96.5,36.5,35.8；ESI-MS calculated for C13H12F3N3O[M+Na]+,306.0825；found306.0820.In this example, compound 24 is a yellow solid with a yield of 82%; melting point = 119.5-122.5°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.40 (s, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.33 (q, J = 6.6, 5.7 Hz, 1H), 7.19 (q, J = 7.2 Hz, 2H), 6.45 (s, 1H), 3.82 (s, 2H), 3.73 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ168.8,161.1(d,J＝244.3Hz),144.3(t,J＝28.4Hz),138.1,132.5(d,J＝4.4Hz),129.5(d,J＝8.1Hz),124.7(d,J＝3.4Hz),122.9(d,J＝15.9Hz),115.5(d, J=21.5Hz), 112.0 (t, J=231.6Hz), 96.5, 36.5, 35.8; ESI-MS calculated for C 13 H 12 F 3 N 3 O[M+Na] + ,306.0825; found306.0820.

实施例25化合物25Example 25 Compound 25

化合物25为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(3-氟苯基)乙酰胺，其化学式如下：Compound 25 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(3-fluorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物25为白色固体,产率84％；熔点＝110.8-112.2℃；1H NMR(400MHz,DMSO-d6)δ10.37(s,1H),7.38(q,J＝7.9Hz,1H),7.18(d,J＝8.5Hz,2H),7.10(t,J＝9.2Hz,1H),6.46(s,1H),3.77(s,2H),3.71(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.2,162.5(d,J＝243.1Hz),144.3(t,J＝28.4Hz),138.5(d,J＝8.0Hz),138.1,130.6(d,J＝8.4Hz),125.9(d,J＝2.7Hz),16.5(d,J＝21.5Hz),114.0(d,J＝20.8Hz),112.0(t,J＝231.6Hz),96.5,42.0,36.5；ESI-MS calculated for C13H12F3N3O[M+Na]+,306.0825；found306.0821.In this example, compound 25 is a white solid with a yield of 84%; melting point = 110.8-112.2°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.37 (s, 1H), 7.38 (q, J = 7.9 Hz, 1H), 7.18 (d, J = 8.5 Hz, 2H), 7.10 (t, J = 9.2 Hz, 1H), 6.46 (s, 1H), 3.77 (s, 2H), 3.71 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.2,162.5(d,J＝243.1Hz),144.3(t,J＝28.4Hz),138.5(d,J＝8.0Hz),138.1,130.6(d,J＝8.4Hz),125.9(d,J＝2.7Hz),16.5(d,J＝21.5Hz),114.0(d,J =20.8Hz), 112.0 (t, J = 231.6Hz), 96.5, 42.0, 36.5; ESI-MS calculated for C 13 H 12 F 3 N 3 O[M+Na] + ,306.0825; found306.0821.

实施例26化合物26Example 26 Compound 26

化合物26为N-(3-二氟甲基)-1-甲基-1H-吡唑-5-基-2-(4-氟苯基)乙酰胺，其化学式如下：Compound 26 is N-(3-difluoromethyl)-1-methyl-1H-pyrazol-5-yl-2-(4-fluorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物26为黄色固体,产率72％；熔点＝129.9-131.0℃；1H NMR(400MHz,DMSO-d6)δ10.36(s,1H),7.41–7.34(m,2H),7.17(t,J＝8.9Hz,2H),6.47(s,1H),3.74(s,2H),3.71(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.6,161.6(d,J＝242.4Hz),144.3(t,J＝28.4Hz),138.1,131.93(d,J＝3.1Hz),131.6(d,J＝8.1Hz),115.5(d,J＝21.2Hz),115.4,111.2(t,J＝231.5Hz),96.5,41.5,36.5；ESI-MS calculated for C13H12F3N3O[M+Na]+,306.0825；found 306.0820.In this example, compound 26 is a yellow solid with a yield of 72%; melting point = 129.9-131.0°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.36 (s, 1H), 7.41–7.34 (m, 2H), 7.17 (t, J = 8.9 Hz, 2H), 6.47 (s, 1H), 3.74 (s, 2H), 3.71 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.6,161.6(d,J＝242.4Hz),144.3(t,J＝28.4Hz),138.1,131.93(d,J＝3.1Hz),131.6(d,J＝8.1Hz),115.5(d,J＝21.2Hz),115.4,111.2(t,J＝231.5Hz) ,96.5,41.5,36.5; ESI-MS calculated for C 13 H 12 F 3 N 3 O[M+Na] + ,306.0825; found 306.0820.

实施例27化合物27Example 27 Compound 27

化合物27为2-(2-氯苯基)-N-(3-二氟甲基)-1-甲基-1H-吡唑-5-基乙酰胺，其化学式如下：Compound 27 is 2-(2-chlorophenyl)-N-(3-difluoromethyl)-1-methyl-1H-pyrazol-5-yl acetamide, and its chemical formula is as follows:

本实施例中化合物27为黄色固体,产率69％；熔点＝146.5-148.1℃；1H NMR(400MHz,DMSO-d6)δ10.17(s,1H),7.19(q,J＝7.8Hz,2H),6.93(d,J＝8.1Hz,1H),6.85(d,J＝14.8Hz,1H),6.38(s,1H),3.72(s,3H),3.67(s,3H),3.63(s,2H)；13C NMR(101MHz,DMSO-d6)δ168.7,144.3(t,J＝28.3Hz),138.1,134.2,133.9,132.8,129.5,129.3,127.6,112.0(t,J＝231.5Hz),96.5,36.6；ESI-MS calculated for C13H12ClF2N3O[M+Na]+,322.0529；found 322.0531.In this example, compound 27 is a yellow solid with a yield of 69%; melting point = 146.5-148.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.17 (s, 1H), 7.19 (q, J = 7.8 Hz, 2H), 6.93 (d, J = 8.1 Hz, 1H), 6.85 (d, J = 14.8 Hz, 1H), 6.38 (s, 1H), 3.72 (s, 3H), 3.67 (s, 3H), 3.63 (s, 2H); 13 C NMR (101 MHz, DMSO-d 6 )δ168.7,144.3(t,J＝28.3Hz),138.1,134.2,133.9,132.8,129.5,129.3,127.6,112.0(t,J＝231.5Hz),96.5,36.6; ESI-MS calculated for C 13 H 12 ClF 2 N 3 O[M+Na] + ,322.0529; found 322.0531.

实施例28化合物28Example 28 Compound 28

化合物28为2-(3-氯苯基)-N-(3-二氟甲基)-1-甲基-1H-吡唑-5-基乙酰胺，其化学式如下：Compound 28 is 2-(3-chlorophenyl)-N-(3-difluoromethyl)-1-methyl-1H-pyrazol-5-yl acetamide, and its chemical formula is as follows:

本实施例中化合物28为白色固体,产率77％；熔点＝134.9-137.1℃；1H NMR(400MHz,DMSO-d6)δ10.37(s,1H),7.42(s,1H),7.40–7.34(m,2H),7.30(d,J＝7.2Hz,1H),6.87(s,1H),6.46(s,1H),3.77(s,2H),3.72(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.2,144.3(t,J＝28.4Hz),138.2,133.3,130.6,129.7,128.5,127.2,112.0(t,J＝231.6Hz),96.5,41.8,36.5；ESI-MS calculated for C13H12ClF2N3O[M+Na]+,322.0529；found322.0530.In this example, compound 28 is a white solid with a yield of 77%; melting point = 134.9-137.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.37 (s, 1H), 7.42 (s, 1H), 7.40–7.34 (m, 2H), 7.30 (d, J = 7.2 Hz, 1H), 6.87 (s, 1H), 6.46 (s, 1H), 3.77 (s, 2H), 3.72 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.2,144.3(t,J＝28.4Hz),138.2,133.3,130.6,129.7,128.5,127.2,112.0(t,J＝231.6Hz),96.5,41.8,36.5; ESI-MS calculated for C 13 H 12 ClF 2 N 3 O[M+Na] + ,322.0529;found322.0530.

实施例29化合物29Example 29 Compound 29

化合物29为2-(4-氯苯基)-N-(3-二氟甲基)-1-甲基-1H-吡唑-5-基)乙酰胺，其化学式如下：Compound 29 is 2-(4-chlorophenyl)-N-(3-difluoromethyl)-1-methyl-1H-pyrazol-5-yl)acetamide, and its chemical formula is as follows:

本实施例中化合物29为黄色固体,产率75％；熔点＝146.5-148.1℃；1H NMR(400MHz,DMSO-d6)δ10.29(s,1H),7.31(d,J＝9.5Hz,4H),δ6.80(t,J＝54.6Hz,1H),6.38(s,1H),3.67(s,2H),3.64(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.4,144.3(t,J＝28.6Hz),138.1,134.8,131.9,131.6,128.7,112.0(t,J＝231.5Hz),96.5,41.7,36.5；ESI-MScalculated for C13H12ClF2N3O[M+Na]+,322.0529；found 322.0530.In this example, compound 29 is a yellow solid with a yield of 75%; melting point = 146.5-148.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.29 (s, 1H), 7.31 (d, J = 9.5 Hz, 4H), δ 6.80 (t, J = 54.6 Hz, 1H), 6.38 (s, 1H), 3.67 (s, 2H), 3.64 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 169.4, 144.3 (t, J = 28.6 Hz), 138.1, 134.8, 131.9, 131.6, 128.7, 112.0 (t, J = 231.5 Hz), 96.5, 41.7, 36.5; ESI-MS calculated for C 13 H 12 ClF 2 N 3 O[M+Na] + ,322.0529; found 322.0530.

实施例30化合物30Example 30 Compound 30

化合物30为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(2-三氟甲基苯基)乙酰胺，其化学式如下：Compound 30 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(2-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物30为黄色固体,产率66％；熔点＝171.4-173.4℃；1H NMR(400MHz,DMSO-d6)δ10.40(s,1H),7.73(s,1H),7.66(d,J＝15.0Hz,1H),7.52(dd,J＝18.9,7.7Hz,2H),6.43(s,1H),4.01(s,2H),3.73(s,3H)；13C NMR(101MHz,DMSO-d6)δ168.8,144.3(t,J＝28.4Hz),138.1,134.0,133.7,133.7,132.8,128.0(q,J＝29.4Hz),127.9,126.3,126.2(q,J＝5.5Hz),123.6,112.0(t,J＝231.6Hz),39.2,36.5；ESI-MS calculated forC14H12F5N3O[M+Na]+,356.0793；found 356.0792.In this example, compound 30 is a yellow solid with a yield of 66%; melting point = 171.4-173.4°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.40 (s, 1H), 7.73 (s, 1H), 7.66 (d, J = 15.0 Hz, 1H), 7.52 (dd, J = 18.9, 7.7 Hz, 2H), 6.43 (s, 1H), 4.01 (s, 2H), 3.73 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ168.8,144.3(t,J＝28.4Hz),138.1,134.0,133.7,133.7,132.8,128.0(q,J＝29.4Hz),127.9,126.3,126.2(q,J＝5.5Hz),123.6,112.0(t,J＝231.6Hz) ,39.2,36.5; ESI-MS calculated forC 14 H 12 F 5 N 3 O[M+Na] + ,356.0793; found 356.0792.

实施例31化合物31Example 31 Compound 31

化合物31为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(3-三氟甲基苯基)乙酰胺，其化学式如下：Compound 31 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(3-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物31为白色固体,产率63％；熔点＝145.2-146.3℃；1H NMR(400MHz,Chloroform-d)δ7.32(t,J＝7.5Hz,1H),7.21–7.11(m,3H),6.94(s,1H),6.40(s,1H),3.74(s,2H),3.59(s,3H),2.39(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.2,139.2(q,J＝37.6Hz),138.5,137.0,134.0,129.8,129.5(q,J＝30.9Hz),126.5(q,J＝3.7Hz),126.1,124.0,124.0,123.2(q,J＝25.7Hz),120.4,97.3,41.8,36.9；ESI-MS calculated forC14H12F5N3O[M+Na]+,356.0793；found 356.0793.In this example, compound 31 is a white solid with a yield of 63%; melting point = 145.2-146.3°C; 1 H NMR (400 MHz, Chloroform-d) δ7.32 (t, J = 7.5 Hz, 1H), 7.21-7.11 (m, 3H), 6.94 (s, 1H), 6.40 (s, 1H), 3.74 (s, 2H), 3.59 (s, 3H), 2.39 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.2,139.2(q,J＝37.6Hz),138.5,137.0,134.0,129.8,129.5(q,J＝30.9Hz),126.5(q,J＝3.7Hz),126.1,124.0,124.0,123.2(q,J＝25.7Hz),120.4 ,97.3,41.8,36.9; ESI-MS calculated forC 14 H 12 F 5 N 3 O[M+Na] + ,356.0793; found 356.0793.

实施例32化合物32Example 32 Compound 32

化合物32为N-(3-二氟甲基)-1-甲基吡唑-5-基-2-(4-三氟甲基苯基)乙酰胺，其化学式如下：Compound 32 is N-(3-difluoromethyl)-1-methylpyrazol-5-yl-2-(4-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物32为黄色固体,产率67％；熔点＝136.4-138.0℃；1H NMR(400MHz,DMSO-d6)δ10.45(s,1H),7.71(d,J＝8.0Hz,2H),7.57(d,J＝7.9Hz,2H),6.47(d,J＝3.8Hz,1H),3.87(s,2H),3.73(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.0,144.3(t,J＝28.4Hz),140.6,138.0,130.6,127.9(q,J＝32.0Hz),125.6,124.8(d,J＝271.9Hz),112.0(t,J＝231.5Hz),96.5,42.1,36.5；ESI-MS calculated for C14H12F5N3O[M+Na]+,356.0793；found 356.0791.In this example, compound 32 is a yellow solid with a yield of 67%; melting point = 136.4-138.0°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.45 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 7.9 Hz, 2H), 6.47 (d, J = 3.8 Hz, 1H), 3.87 (s, 2H), 3.73 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.0,144.3(t,J＝28.4Hz),140.6,138.0,130.6,127.9(q,J＝32.0Hz),125.6,124.8(d,J＝271.9Hz),112.0(t,J＝231.5Hz),96.5,42.1,36.5; ESI-MS calculated for C 14 H 12 F 5 N 3 O[M+Na] + ,356.0793; found 356.0791.

实施例33化合物33Example 33 Compound 33

化合物33为2，4-二氯苯基-N-1-甲基-3-三氟甲基吡唑-5-乙酰胺，其化学式如下：Compound 33 is 2,4-dichlorophenyl-N-1-methyl-3-trifluoromethylpyrazole-5-acetamide, and its chemical formula is as follows:

本实施例中化合物33为白色固体,产率75％；熔点＝192.1-195.3℃；1H NMR(400MHz,DMSO-d6)δ10.55(s,1H),7.63(s,1H),7.48(d,J＝8.3Hz,1H),7.43(d,J＝9.6Hz,1H),6.63(s,1H),3.93(s,2H),3.79(s,3H)；13C NMR(101MHz,DMSO-d6)δ168.4,139.2(q,J＝37.4Hz),138.5,135.2,134.1,133.0,132.9,129.0,127.7,121.8(q,J＝268.0Hz),97.4,37.0；ESI-MS calculated for C13H11Cl2F3N3O[M+H]+,352.0226；found352.0226.In this example, compound 33 is a white solid with a yield of 75%; melting point = 192.1-195.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.55 (s, 1H), 7.63 (s, 1H), 7.48 (d, J = 8.3 Hz, 1H), 7.43 (d, J = 9.6 Hz, 1H), 6.63 (s, 1H), 3.93 (s, 2H), 3.79 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ168.4,139.2(q,J＝37.4Hz),138.5,135.2,134.1,133.0,132.9,129.0,127.7,121.8(q,J＝268.0Hz),97.4,37.0; ESI-MS calculated for C 13 H 11 Cl 2 F 3 N 3 O[M+H ] + ,352.0226; found352.0226.

实施例34化合物34Example 34 Compound 34

化合物34为2-(3，4-二氯苯基)-N-(1-甲基-3-三氟甲基)-1H-吡唑-5-基乙酰胺，其化学式如下：Compound 34 is 2-(3,4-dichlorophenyl)-N-(1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl acetamide, and its chemical formula is as follows:

本实施例中化合物34为白色固体,产率72％；熔点＝197.6-198.9℃；1H NMR(400MHz,DMSO-d6)δ10.49(s,1H),7.62(s,2H),7.32(s,1H),6.65(s,1H),3.80(s,2H),3.77(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.0,139.2(q,J＝37.3Hz),138.4,136.7,131.9,131.2,130.9,130.3,129.9,121.8(q,J＝268.0Hz),97.3,41.1,37.0；ESI-MS calculatedfor C13H11Cl2F3N3O[M+H]+,352.0226；found 352.0226.In this example, compound 34 is a white solid with a yield of 72%; melting point = 197.6-198.9°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.49 (s, 1H), 7.62 (s, 2H), 7.32 (s, 1H), 6.65 (s, 1H), 3.80 (s, 2H), 3.77 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 169.0, 139.2 (q, J = 37.3 Hz), 138.4, 136.7, 131.9, 131.2, 130.9, 130.3, 129.9, 121.8 (q, J = 268.0 Hz), 97.3, 41.1, 37.0; ESI-MS calculated for C 13 H 11 Cl 2 F 3 N 3 O[M+H] + ,352.0226; found 352.0226.

实施例35化合物35Example 35 Compound 35

化合物35为2-(3，5-二氯苯基)-N-(1-甲基-3-三氟甲基)吡唑-5-乙酰胺，其化学式如下：Compound 35 is 2-(3,5-dichlorophenyl)-N-(1-methyl-3-trifluoromethyl)pyrazole-5-acetamide, and its chemical formula is as follows:

本实施例中化合物35为白色固体,产率79％；熔点＝190.2-193.3℃；1H NMR(400MHz,DMSO-d6)δ10.51(s,1H),7.53(s,1H),7.41(s,2H),6.66(s,1H),3.82(s,2H),3.78(s,3H)；13C NMR(101MHz,DMSO-d6)δ168.8,139.8,139.7,139.2(q,J＝37.4Hz),138.7,138.4,134.2,128.8,126.9,125.8,121.8(q,J＝268.0Hz),117.8,97.3,41.3,37.0；ESI-MScalculated for C13H11Cl2F3N3O[M+H]+,352.0226；found 352.0222.In this example, compound 35 is a white solid with a yield of 79%; melting point = 190.2-193.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.51 (s, 1H), 7.53 (s, 1H), 7.41 (s, 2H), 6.66 (s, 1H), 3.82 (s, 2H), 3.78 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ168.8,139.8,139.7,139.2(q,J＝37.4Hz),138.7,138.4,134.2,128.8,126.9,125.8,121.8(q,J＝268.0Hz),117.8,97.3,41.3,37.0; ESI-MScalculated for C 13 H 11 Cl 2 F 3 N 3 O[M+H] + ,352.0226; found 352.0222.

实施例36化合物36Example 36 Compound 36

化合物36为2-(2，4-双三氟甲基)苯基-N-(1-甲基-3-三氟甲基)吡唑-5-乙酰胺，其化学式如下：Compound 36 is 2-(2,4-bistrifluoromethyl)phenyl-N-(1-methyl-3-trifluoromethyl)pyrazole-5-acetamide, and its chemical formula is as follows:

本实施例中化合物36为白色固体,产率61％；熔点＝168.2-170.1℃；1H NMR(400MHz,DMSO-d6)δ10.62(s,1H),8.10(s,1H),8.01(s,1H),7.83(s,1H),6.62(s,1H),4.15(s,2H),3.79(s,3H).13C NMR(101MHz,DMSO-d6)δ168.2,139.4(q,J＝37.4Hz),138.7,135.5,129.5,129.3,128.8(q,J＝31.7Hz),124.0(q,J＝274.1Hz),123.9(q,J＝272.3Hz),123.0,121.7(q,J＝267.9Hz),117.7,97.3,39.1,36.8；ESI-MS calculated forC15H11F9N3O[M+H]+,420.0753；found 420.0754.In this example, compound 36 is a white solid with a yield of 61%; melting point = 168.2-170.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.62 (s, 1H), 8.10 (s, 1H), 8.01 (s, 1H), 7.83 (s, 1H), 6.62 (s, 1H), 4.15 (s, 2H), 3.79 (s, 3H). 13 C NMR (101 MHz, DMSO-d 6 )δ168.2,139.4(q,J＝37.4Hz),138.7,135.5,129.5,129.3,128.8(q,J＝31.7Hz),124.0(q,J＝274.1Hz),123.9(q,J＝272.3Hz),123.0,121.7(q,J＝267. 9Hz),117.7,97.3,39.1,36.8; ESI-MS calculated forC 15 H 11 F 9 N 3 O[M+H] + ,420.0753; found 420.0754.

实施例37化合物37Example 37 Compound 37

化合物37为2-(3，5-双三氟甲基苯基)-N-(1-甲基-3-三氟甲基)吡唑-5-乙酰胺，其化学式如下：Compound 37 is 2-(3,5-bis(trifluoromethylphenyl)-N-(1-methyl-3-trifluoromethyl)pyrazole-5-acetamide, and its chemical formula is as follows:

本实施例中化合物37为白色固体,产率65％；熔点＝186.0-188.4℃；1H NMR(400MHz,DMSO-d6)δ10.60(s,1H),8.06(s,2H),8.00(s,1H),6.65(s,1H),4.06(s,2H),3.80(s,3H).13C NMR(101MHz,DMSO-d6)δ168.8,139.3(q,J＝37.4Hz),138.9,138.4,131.1(2C),130.5(q,J＝32.7Hz),123.8(q,J＝272.7Hz)，121.8(q,J＝268.1Hz)，121.0,121.0,120.9，97.3,41.2,36.9；ESI-MS calculated for C15H11F9N3O[M+H]+,420.0753；found 420.0754.In this example, compound 37 is a white solid with a yield of 65%; melting point = 186.0-188.4°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.60 (s, 1H), 8.06 (s, 2H), 8.00 (s, 1H), 6.65 (s, 1H), 4.06 (s, 2H), 3.80 (s, 3H). 13 C NMR (101 MHz, DMSO-d 6 )δ168.8,139.3(q,J＝37.4Hz),138.9,138.4,131.1(2C),130.5(q,J＝32.7Hz),123.8(q,J＝272.7Hz), 121.8(q,J＝268.1Hz), 121.0,121.0,120.9,97.3, 41.2,36.9; ESI-MS calculated for C 15 H 11 F 9 N 3 O[M+H] + ,420.0753; found 420.0754.

实施例38化合物38Example 38 Compound 38

化合物38为N-甲基-3-三氟甲基-1H-吡唑-5-基-2-萘乙酰胺，其化学式如下：Compound 38 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-naphthylacetamide, and its chemical formula is as follows:

本实施例中化合物38为白色固体,产率65％；熔点＝186.4-187.7℃；1H NMR(400MHz,DMSO-d6)δ10.55(s,1H),7.89(d,J＝8.0Hz,3H),7.85(s,1H),7.51(d,J＝6.5Hz,3H),6.66(s,1H),3.93(s,2H),3.78(s,3H)；13C NMR(101MHz,DMSO-d6)δ169.8,139.2(q,J＝37.5Hz),138.6,133.4,133.3,132.4,128.3,128.1,128.1,128.0,127.9,126.6,126.2,121.8(q,J＝268.2Hz),97.4,42.6,37.0；ESI-MS calculated for C17H15F3N3O[M+H]+,334.1162；found 334.1162.In this example, compound 38 is a white solid with a yield of 65%; melting point = 186.4-187.7°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.55 (s, 1H), 7.89 (d, J = 8.0 Hz, 3H), 7.85 (s, 1H), 7.51 (d, J = 6.5 Hz, 3H), 6.66 (s, 1H), 3.93 (s, 2H), 3.78 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ169.8,139.2(q,J＝37.5Hz),138.6,133.4,133.3,132.4,128.3,128.1,128.1,128.0,127.9,126.6,126.2,121.8(q,J＝268.2Hz),97.4,42.6,37. 0; ESI-MS calculated for C 17 H 15 F 3 N 3 O[M+H] + ,334.1162; found 334.1162.

实施例39化合物39Example 39 Compound 39

化合物39为N-(4-氯-1-甲基-3-三氟甲基)-1H-吡唑-5-基-2-(3-氯苯基)乙酰胺，其化学式如下：Compound 39 is N-(4-chloro-1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl-2-(3-chlorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物39为白色固体,产率81％；熔点＝167.1-170.2℃；1H NMR(400MHz,DMSO-d6)δ10.77(s,1H),7.45(s,1H),7.33(s,3H),3.81(s,2H),3.70(s,3H)；13CNMR(101MHz,DMSO-d6)δ170.4,137.9,136.1,135.4(q,J＝36.6Hz),133.4,130.7,129.6,128.4,127.3,120.9(q,J＝268.8Hz),103.2,41.5,37.8；ESI-MS calculated forC13H9Cl2F3N3O[M-H]-,350.0080；found 350.0070.In this example, compound 39 is a white solid with a yield of 81%; melting point = 167.1-170.2°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.77 (s, 1H), 7.45 (s, 1H), 7.33 (s, 3H), 3.81 (s, 2H), 3.70 (s, 3H); 13 CNMR (101 MHz, DMSO-d 6 ) δ 170.4, 137.9, 136.1, 135.4 (q, J = 36.6 Hz), 133.4, 130.7, 129.6, 128.4, 127.3, 120.9 (q, J = 268.8 Hz), 103.2, 41.5, 37.8; ESI-MS calculated for C 13 H 9 Cl 2 F 3 N 3 O [MH] - ,350.0080; found 350.0070.

实施例40化合物40Example 40 Compound 40

化合物40为N-氯-1-甲基-3-三氟甲基-1H-吡唑-5-基-2-(4-氯苯基)乙酰胺，其化学式如下：Compound 40 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-(4-chlorophenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物40为黄色固体,产率79％；熔点＝181.3-183.0℃；1H NMR(400MHz,DMSO-d6)δ10.63(s,1H),7.44–7.36(m,4H),3.78(s,2H),3.69(s,3H)；13C NMR(101MHz,DMSO-d6)δ170.6,136.1,135.4(q,J＝37.0Hz),134.5,132.0,131.6,128.8,120.9(q,J＝268.5Hz),103.2,41.3,37.8；ESI-MS calculated for C13H9Cl2F3N3O[M-H]-,350.0080；found 350.0070.In this example, compound 40 is a yellow solid with a yield of 79%; melting point = 181.3-183.0°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.63 (s, 1H), 7.44–7.36 (m, 4H), 3.78 (s, 2H), 3.69 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 170.6, 136.1, 135.4 (q, J = 37.0 Hz), 134.5, 132.0, 131.6, 128.8, 120.9 (q, J = 268.5 Hz), 103.2, 41.3, 37.8; ESI-MS calculated for C 13 H 9 Cl 2 F 3 N 3 O[MH] - , 350.0080; found 350.0070.

实施例41化合物41Example 41 Compound 41

化合物41为2-(3-氯苯基)-N-(4-氟-1-甲基-3-三氟甲基)-1H-吡唑-5-基乙酰胺，其化学式如下：Compound 41 is 2-(3-chlorophenyl)-N-(4-fluoro-1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl acetamide, and its chemical formula is as follows:

本实施例中化合物41为黄色固体,产率82％；熔点＝119.6-121.0℃；1H NMR(400MHz,DMSO-d6)δ10.43(s,1H),7.36(ddd,J＝28.2,16.5,8.4Hz,4H),3.80(s,2H),3.68(s,3H)；13C NMR(101MHz,DMSO-d6)δ170.3,138.6(d,J＝251.6Hz),137.8,133.4,130.7,129.7,128.5,127.3,125.4(qd,J＝38.2,5.7Hz),124.8(d,J＝22.3Hz),120.7(qd,J＝267.8,3.4Hz),41.4,37.7；ESI-MS calculated for C13H9ClF4N3O[M-H]-,334.0376；found334.0368.In this example, compound 41 is a yellow solid with a yield of 82%; melting point = 119.6-121.0°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.43 (s, 1H), 7.36 (ddd, J = 28.2, 16.5, 8.4 Hz, 4H), 3.80 (s, 2H), 3.68 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ170.3,138.6(d,J＝251.6Hz),137.8,133.4,130.7,129.7,128.5,127.3,125.4(qd,J＝38.2,5.7Hz),124.8(d,J＝22.3Hz),120.7(qd,J＝267.8,3.4Hz) ,41.4,37.7; ESI-MS calculated for C 13 H 9 ClF 4 N 3 O[MH] - ,334.0376; found334.0368.

实施例42化合物42Example 42 Compound 42

化合物42为2-(4-氯苯基)-N-(4-氟-1-甲基-3-三氟甲基)-1H-吡唑-5-基乙酰胺，其化学式如下：Compound 42 is 2-(4-chlorophenyl)-N-(4-fluoro-1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl acetamide, and its chemical formula is as follows:

本实施例中化合物42为黄色固体,产率85％；熔点＝133.5-136.2℃；1H NMR(400MHz,DMSO-d6)δ10.51(s,1H),7.40(s,4H),3.78(s,2H),3.67(s,3H).13C NMR(101MHz,DMSO-d6)δ170.5,138.5(d,J＝252.2Hz),134.4,132.0,131.6,128.8,125.4(qd,J＝38.4,6.4Hz),124.8(d,J＝22.4Hz),120.7(qd,J＝267.8,3.5Hz),41.2,37.7；ESI-MScalculated for C13H9ClF4N3O[M-H]-,334.0376；found 334.0368.In this example, compound 42 is a yellow solid with a yield of 85%; melting point = 133.5-136.2°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.51 (s, 1H), 7.40 (s, 4H), 3.78 (s, 2H), 3.67 (s, 3H). 13 C NMR (101 MHz, DMSO-d 6 ) δ 170.5, 138.5 (d, J = 252.2 Hz), 134.4, 132.0, 131.6, 128.8, 125.4 (qd, J = 38.4, 6.4 Hz), 124.8 (d, J = 22.4 Hz), 120.7 (qd, J = 267.8, 3.5 Hz), 41.2, 37.7; ESI-MS calculated for C 13 H 9 ClF 4 N 3 O[MH] - ,334.0376; found 334.0368.

实施例43化合物43Example 43 Compound 43

化合物43为N-(4-氯-1-甲基-3-三氟甲基)吡唑-5-基-2-(3(三氟甲基)苯基)乙酰胺，其化学式如下：Compound 43 is N-(4-chloro-1-methyl-3-trifluoromethyl)pyrazol-5-yl-2-(3(trifluoromethyl)phenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物43为白色固体,产率65％；熔点＝161.2-163.3℃；1H NMR(400MHz,DMSO-d6)δ10.56(s,1H),7.74(s,1H),7.69–7.57(m,3H),3.92(s,2H),3.71(s,3H)；13C NMR(101MHz,DMSO-d6)δ170.4,136.8,136.0,135.4(q,J＝37.2Hz),134.0,129.9,129.7,129.4,126.3(q,J＝3.9Hz),124.1(q,J＝3.9Hz),122.8(q,J＝110.5Hz),103.2,41.5,37.8；ESI-MS calculated for C14H9ClF6N3O[M-H]-,384.0344；found 384.0335.In this example, compound 43 is a white solid with a yield of 65%; melting point = 161.2-163.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.56 (s, 1H), 7.74 (s, 1H), 7.69-7.57 (m, 3H), 3.92 (s, 2H), 3.71 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ170.4,136.8,136.0,135.4(q,J＝37.2Hz),134.0,129.9,129.7,129.4,126.3(q,J＝3.9Hz),124.1(q,J＝3.9Hz),122.8(q,J＝110.5Hz),103.2,41.5, 37.8; ESI-MS calculated for C 14 H 9 ClF 6 N 3 O[MH] - ,384.0344; found 384.0335.

实施例44化合物44Example 44 Compound 44

化合物44为N-氯-1-甲基-3-三氟甲基-1H-吡唑-5-基-2-(4(三氟甲基)苯基)乙酰胺，其化学式如下：Compound 44 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-(4(trifluoromethyl)phenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物44为黄色固体,产率62％；熔点＝174.2-175.5℃；1H NMR(400MHz,DMSO-d6)δ10.57(s,1H),7.72(d,J＝8.1Hz,2H),7.59(s,2H),3.90(s,2H),3.70(s,3H)；13C NMR(101MHz,DMSO-d6)δ170.3,145.8,140.2,136.0,135.4(q,J＝37.3Hz),130.6,128.0(q,J＝31.7Hz),125.7(q,J＝3.8Hz),125.6,124.9,122.8(q,J＝120.7Hz),119.6,103.2,41.7,37.8；ESI-MS calculated for C14H9ClF6N3O[M-H]-,384.0344；found384.0334.,37.8；ESI-MS calculated for C14H9ClF6N3O[M-H]-,384.0344；found384.0334.In this example, compound 44 is a yellow solid with a yield of 62%; melting point = 174.2-175.5°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.57 (s, 1H), 7.72 (d, J = 8.1 Hz, 2H), 7.59 (s, 2H), 3.90 (s, 2H), 3.70 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ170.3,145.8,140.2,136.0,135.4(q,J＝37.3Hz),130.6,128.0(q,J＝31.7Hz),125.7(q,J＝3.8Hz),125.6,124.9,122.8(q,J＝120.7Hz),119.6,103. 2,41.7,37.8; ESI-MS calculated for C 14 H 9 ClF 6 N 3 O[MH] - ,384.0344; found384.0334.,37.8; ESI-MS calculated for C 14 H 9 ClF 6 N 3 O[MH] - ,384.0344; found384.0334.

实施例45化合物45Example 45 Compound 45

化合物45为N-(4-氟-1-甲基-3-三氟甲基)-1H-吡唑-5-基-2-(3-三氟甲基苯基)乙酰胺，其化学式如下：Compound 45 is N-(4-fluoro-1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl-2-(3-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物45为黄色固体,产率71％；熔点＝172.5-173.6℃；1H NMR(400MHz,DMSO-d6)δ10.47(s,1H),7.73(s,1H),7.65(d,J＝7.7Hz,2H),7.59(dd,J＝8.7,6.4Hz,1H),3.91(s,2H),3.69(s,3H)；13CNMR(101MHz,DMSO-d6)δ170.4,138.6(d,J＝253.0Hz),136.7,134.0,129.8,129.5(q,J＝31.5Hz),126.4(q,J＝3.8Hz),126.0,124.8(q,J＝22.3Hz),124.0(q,J＝3.7Hz),122.1(d,J＝3.5Hz),119.4(d,J＝3.4Hz),41.4,37.7；ESI-MS calculated for C14H9F7N3O[M-H]-,368.0639；found 368.0628.In this example, compound 45 is a yellow solid with a yield of 71%; melting point = 172.5-173.6°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.47 (s, 1H), 7.73 (s, 1H), 7.65 (d, J = 7.7 Hz, 2H), 7.59 (dd, J = 8.7, 6.4 Hz, 1H), 3.91 (s, 2H), 3.69 (s, 3H); 13 CNMR (101 MHz, DMSO-d 6 )δ170.4,138.6(d,J＝253.0Hz),136.7,134.0,129.8,129.5(q,J＝31.5Hz),126.4(q,J＝3.8Hz),126.0,124.8(q,J＝22.3Hz),124.0(q,J＝3.7Hz),122.1( d,J＝3.5Hz),119.4(d,J＝3.4Hz),41.4,37.7; ESI-MS calculated for C 14 H 9 F 7 N 3 O[MH] - ,368.0639; found 368.0628.

实施例46化合物46Example 46 Compound 46

化合物46为N-(4-氟-1-甲基-3-三氟甲基)-1H-吡唑-5-基-2-(4-三氟甲基苯基)乙酰胺，其化学式如下：Compound 46 is N-(4-fluoro-1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl-2-(4-trifluoromethylphenyl)acetamide, and its chemical formula is as follows:

本实施例中化合物46为白色固体,产率66％；熔点＝169.2-172.1℃；1H NMR(400MHz,DMSO-d6)δ10.50(s,1H),7.72(d,J＝8.0Hz,2H),7.59(s,2H),3.90(s,2H),3.69(s,3H)；13C NMR(101MHz,DMSO-d6)δ170.2,140.2,138.6(d,J＝252.7Hz),130.6,128.0(q,J＝31.9Hz),125.7,124.8(q,J＝22.3Hz),120.7(qd,J＝268.0,3.1Hz),41.7,37.7；ESI-MScalculated for C14H9F7N3O[M-H]-,368.0639；found 368.0625.In this example, compound 46 is a white solid with a yield of 66%; melting point = 169.2-172.1°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.50 (s, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.59 (s, 2H), 3.90 (s, 2H), 3.69 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 170.2, 140.2, 138.6 (d, J = 252.7 Hz), 130.6, 128.0 (q, J = 31.9 Hz), 125.7, 124.8 (q, J = 22.3 Hz), 120.7 (qd, J = 268.0, 3.1 Hz), 41.7, 37.7; ESI-MS calculated for C 14 H 9 F 7 N 3 O[MH] - ,368.0639; found 368.0625.

实施例47化合物47Example 47 Compound 47

化合物47为N-氯-1-甲基-3-三氟甲基-1H-吡唑-5-基-2-间甲苯基乙酰胺，其化学式如下：Compound 47 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-m-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物47为黄色固体,产率81％；熔点＝106.2-108.5℃；1H NMR(400MHz,Chloroform-d)δ7.32(t,J＝7.8Hz,1H),7.17(t,J＝8.7Hz,3H),6.88(s,1H),3.77(s,2H),3.72(s,3H),2.38(s,3H)；13C NMR(101MHz,Chloroform-d)δ170.6,139.5,133.5(q,J＝41.9Hz),130.2,129.5,129.0,126.4,120.2(q,J＝269.6Hz),103.7,43.5,37.9,21.4；ESI-MS calculated for C14H12ClF3N3O[M-H]-,330.0626；found 330.0618.In this example, compound 47 is a yellow solid with a yield of 81%; melting point = 106.2-108.5°C; 1 H NMR (400 MHz, Chloroform-d) δ7.32 (t, J = 7.8 Hz, 1H), 7.17 (t, J = 8.7 Hz, 3H), 6.88 (s, 1H), 3.77 (s, 2H), 3.72 (s, 3H), 2.38 (s, 3H); 13 C NMR (101 MHz, Chloroform-d) δ170.6, 139.5, 133.5 (q, J = 41.9 Hz), 130.2, 129.5, 129.0, 126.4, 120.2 (q, J = 269.6 Hz), 103.7, 43.5, 37.9, 21.4; ESI-MS calculated for C 14 H 12 ClF 3 N 3 O[MH] - ,330.0626; found 330.0618.

实施例48化合物48Example 48 Compound 48

化合物48为N-氯-1-甲基-3-三氟甲基-1H-吡唑-5-基-2-对甲苯基乙酰胺，其化学式如下：Compound 48 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-p-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物48为黄色固体,产率76％；熔点＝147.2-150.3℃；1H NMR(400MHz,DMSO-d6)δ10.48(s,1H),7.24(d,J＝7.8Hz,2H),7.15(d,J＝7.9Hz,2H),3.70(s,2H),3.67(s,3H),2.29(s,3H)；13C NMR(101MHz,DMSO-d6)δ171.1,136.3,136.2,135.4(q,J＝37.1Hz),132.4,129.5,120.9(q,J＝268.8Hz),103.2,41.8,37.7,21.1；ESI-MScalculated for C14H12ClF3N3O[M-H]-,330.0626；found 330.0617.1H NMR(400MHz,DMSO-d6)δ10.48(s,1H),7.24(d,J＝7.8Hz,2H),7.15(d,J＝7.9Hz,2H),3.70(s,2H),3.67(s,3H),2.29(s,3H)；13C NMR(101MHz,DMSO-d6)δ171.1,136.3,136.2,135.4(q,J＝37.1Hz),132.4,129.5,120.9(q,J＝268.8Hz),103.2,41.8,37.7,21.1；ESI-MS calculated forC14H12ClF3N3O[M-H]-,330.0626；found 330.0617.In this example, compound 48 is a yellow solid with a yield of 76%; melting point = 147.2-150.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.48 (s, 1H), 7.24 (d, J = 7.8 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 3.70 (s, 2H), 3.67 (s, 3H), 2.29 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 ) δ 171.1, 136.3, 136.2, 135.4 (q, J = 37.1 Hz), 132.4, 129.5, 120.9 (q, J = 268.8 Hz), 103.2, 41.8, 37.7, 21.1; ESI-MS calculated for C 14 H 12 ClF 3 N 3 O[MH] - ,330.0626; found 330.0617. 1 H NMR (400MHz, DMSO-d 6 ) δ 10.48 (s, 1H), 7.24 (d, J = 7.8Hz, 2H), 7.15 (d, J = 7.9Hz, 2H), 3.70 (s, 2H), 3.67 (s, 3 H), 2.29 (s, 3H); 13 C NMR (101MHz, DMSO-d 6 ) δ 171.1, 136.3, 136.2, 135.4 (q, J = 37.1Hz), 132.4, 129.5, 120.9 (q, J = 268.8Hz), 103.2, 41.8, 37.7, 21.1; ESI-MS calculated forC 14 H 12 ClF 3 N 3 O[MH] - ,330.0626; found 330.0617.

实施例49化合物49Example 49 Compound 49

化合物49为N-(4-氟-1-甲基-3-三氟甲基)-1H-吡唑-5-基-2-间甲苯基乙酰胺，其化学式如下：Compound 49 is N-(4-fluoro-1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl-2-m-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物49为白色固体,产率85％；熔点＝101.0-103.5℃；1H NMR(400MHz,Chloroform-d)δ7.30(t,J＝7.5Hz,1H),7.15(t,J＝12.8Hz,3H),6.93(s,1H),3.74(s,2H),3.64(s,3H),2.38(s,3H)；13CNMR(101MHz,DMSO-d6)δ166.2,134.7,134.4(d,J＝257.1Hz),128.5,125.3,124.6,124.2,122.3(qd,J＝39.9,6.0Hz),121.5,117.7(q,J＝22.2Hz),38.5,32.6,16.6；ESI-MS calculated for C14H12F4N3O[M-H]-,314.0922；found314.0913.In this example, compound 49 is a white solid with a yield of 85%; melting point = 101.0-103.5°C; 1 H NMR (400 MHz, Chloroform-d) δ 7.30 (t, J = 7.5 Hz, 1H), 7.15 (t, J = 12.8 Hz, 3H), 6.93 (s, 1H), 3.74 (s, 2H), 3.64 (s, 3H), 2.38 (s, 3H); 13 CNMR (101 MHz, DMSO-d 6 )δ166.2,134.7,134.4(d,J＝257.1Hz),128.5,125.3,124.6,124.2,122.3(qd,J＝39.9,6.0Hz),121.5,117.7(q,J＝22.2Hz),38.5,32.6,16.6; ESI-MS calculated for C 14 H 12 F 4 N 3 O[MH] - ,314.0922; found314.0913.

实施例50化合物50Example 50 Compound 50

化合物50为N-(4-氟-1-甲基-3-三氟甲基)-1H-吡唑-5-基-2-对甲苯基乙酰胺，其化学式如下：Compound 50 is N-(4-fluoro-1-methyl-3-trifluoromethyl)-1H-pyrazol-5-yl-2-p-tolylacetamide, and its chemical formula is as follows:

本实施例中化合物50为黄色固体,产率77％；熔点＝126.2-128.3℃；1H NMR(400MHz,DMSO-d6)δ10.34(s,1H),7.22(d,J＝7.8Hz,2H),7.15(d,J＝7.9Hz,2H),3.68(s,2H),3.65(s,3H),2.28(s,3H)；13C NMR(101MHz,DMSO-d6)δ171.0,138.6(d,J＝250.9Hz),136.4,132.3,129.5,129.4,126.0,125.9,125.4(qd,J＝38.6,6.1Hz),124.9(d,J＝22.3Hz),120.7(qd,J＝267.8,3.5Hz),41.8,37.6,21.1.ESI-MS calculated forC14H12F4N3O[M-H]-,314.0922；found 314.0913.In this example, compound 50 is a yellow solid with a yield of 77%; melting point = 126.2-128.3°C; 1 H NMR (400 MHz, DMSO-d 6 ) δ 10.34 (s, 1H), 7.22 (d, J = 7.8 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 3.68 (s, 2H), 3.65 (s, 3H), 2.28 (s, 3H); 13 C NMR (101 MHz, DMSO-d 6 )δ171.0,138.6(d,J＝250.9Hz),136.4,132.3,129.5,129.4,126.0,125.9,125.4(qd,J＝38.6,6.1Hz),124.9(d,J＝22.3Hz),120.7(qd,J＝267.8,3.5Hz ),41.8,37.6,21.1.ESI-MS calculated forC 14 H 12 F 4 N 3 O[MH] - ,314.0922; found 314.0913.

实施例1～50中合成的含氟吡唑苯乙酰胺类衍生物(化合物编号1到50)对供试植物病原真菌的抑制作用。The inhibitory effects of the fluorine-containing pyrazole phenylacetamide derivatives (compound numbers 1 to 50) synthesized in Examples 1 to 50 on the tested plant pathogenic fungi.

1.实验对象1. Experimental subjects

实施例1～50中合成的含氟吡唑苯乙酰胺类衍生物Fluorine-containing pyrazole benzene acetamide derivatives synthesized in Examples 1 to 50

2.实验方法2. Experimental Methods

采用菌丝线性生长速率法，测定了化合物1～化合物50在50mg/L浓度下对种供试植物病原真菌的体外抑制活性。所选真菌由西北农林科技大学农药学研究所提供。The mycelium linear growth rate method was used to determine the in vitro inhibitory activity of compounds 1 to 50 against the tested plant pathogenic fungi at a concentration of 50 mg/L. The selected fungi were provided by the Institute of Pesticides of Northwest Agriculture and Forestry University.

以50mg/L的氟唑菌酰胺溶液为阳性对照，以5％的DMSO水溶液作为空白对照，将已准确称量的待测化合物完全溶于5％的DMSO(v/v)水溶液中，将10mL待测液或对照液与90mL无菌PDA培养基在50℃快速混匀，得到质量浓度为25mg/L的含药液；将其趁热倒入已灭菌的培养皿内，每皿10mL，冷却备用。把供试植物病原真菌(菌饼直径5mm)接种到上述培养皿中，每个测试组设3个平行；将其置于25℃的恒温培养箱中培养72h后，采用十字交叉法测量菌落直径(mm)，按式(1)计算菌丝生长抑制率(IR)：IR(％)＝[(dc-d0)-(ds-d0)]/(dc-d0)×100(1)；With 50 mg/L flupyraclostrobin solution as positive control and 5% DMSO aqueous solution as blank control, the accurately weighed test compound is completely dissolved in 5% DMSO (v/v) aqueous solution, 10 mL of the test solution or control solution is quickly mixed with 90 mL of sterile PDA medium at 50°C to obtain a drug-containing solution with a mass concentration of 25 mg/L; the solution is poured into a sterilized culture dish while hot, 10 mL per dish, and cooled for use. The plant pathogenic fungi (dice cake diameter 5 mm) are inoculated into the above culture dish, and 3 parallels are set for each test group; the test dish is placed in a constant temperature incubator at 25°C for 72 hours, and the colony diameter (mm) is measured by the cross method, and the mycelium growth inhibition rate (IR) is calculated according to formula (1): IR (%) = [(d c -d 0 )-(ds-d 0 )]/(d c -d 0 )×100(1);

式中：d0为菌饼直径(5mm)，dc为空白对照组菌落平均直径(mm)，ds为样品组菌落平均直径(mm)。Where: d0 is the diameter of the bacterial cake (5 mm), dc is the average diameter of the colonies in the blank control group (mm), and ds is the average diameter of the colonies in the sample group (mm).

3.实验结果如表1所示3. Experimental results are shown in Table 1

表1实施例1～50中合成含氟吡唑苯乙酰胺类衍生物的体外抑菌活性a(抑制率，％)(50mg/L)Table 1 In vitro antibacterial activity of the fluorine-containing pyrazole benzene acetamide derivatives synthesized in Examples 1 to 50 (inhibition rate, %) (50 mg/L)

a表中数据为三次数据的平均值；S.s.b S.sclerotiorum；V.m.d V.mali；G.gfG.graminis；R.sg R.solaniThe data in table a are the average of three data; Ss b S. sclerotiorum; Vm d V. mali; Gg f G. graminis; Rs g R. solani

从表1可以看出，在50mg/L浓度下，化合物42对小麦全蚀病菌的活性最为优异，其抑制率高达100％，化合物16对油菜菌核病菌的抑制率为91.3％，化合物42对苹果腐烂病菌的活性最佳，其抑制率为86.9％，化合物49对水稻纹枯病菌的抑制率为92.8％。As can be seen from Table 1, at a concentration of 50 mg/L, compound 42 has the best activity against wheat take-all pathogen, with an inhibition rate of up to 100%, compound 16 has an inhibition rate of 91.3% against rapeseed sclerotinia pathogen, compound 42 has the best activity against apple rot pathogen, with an inhibition rate of 86.9%, and compound 49 has an inhibition rate of 92.8% against rice sheath blight pathogen.

综合上述，本申请经化学合成制备的50种含氟吡唑苯乙酰胺类衍生物均具有抗真菌活性，尤其是对小麦全蚀病菌和水稻纹枯病菌表现出尤为显著的抑菌活性，这为制备以含氟吡唑苯乙酰胺类衍生物为主要抗真菌活性成分的杀菌剂奠定了基础。In summary, the 50 fluorine-containing pyrazole phenylacetamide derivatives prepared by chemical synthesis in the present application all have antifungal activity, especially against wheat take-all pathogen and rice sheath blight pathogen, which lays a foundation for the preparation of fungicides with fluorine-containing pyrazole phenylacetamide derivatives as the main antifungal active ingredients.

以上说明书中描述的只是本发明的具体实施方式，各种举例说明不对本发明的实质内容构成限制，所属技术领域的普通技术人员在阅读了说明书后可以对以前所述的具体实施方式做修改或变形，而不背离发明的实质和范围。The above description only describes the specific implementation mode of the present invention. Various examples do not limit the essential content of the present invention. After reading the description, ordinary technicians in the relevant technical field can modify or deform the specific implementation modes described above without departing from the essence and scope of the invention.

Claims (2)

1.一种含氟吡唑苯乙酰胺类衍生物，其特征在于：所述含氟吡唑苯乙酰胺类衍生物选自如下化合物：1. A fluorine-containing pyrazole phenylacetamide derivative, characterized in that: the fluorine-containing pyrazole phenylacetamide derivative is selected from the following compounds: 2.一种如权利要求1所述的含氟吡唑苯乙酰胺类衍生物的应用，其特征在于：所述含氟吡唑苯乙酰胺类衍生物在抗真菌活性方面的应用。2. An application of the fluorine-containing pyrazole phenylacetamide derivative as claimed in claim 1, characterized in that the fluorine-containing pyrazole phenylacetamide derivative is used in antifungal activity.
CN202310109208.6A 2023-02-14 2023-02-14 Fluorine-containing pyrazole phenylacetamide derivative and application thereof Active CN116003323B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202310109208.6A CN116003323B (en) 2023-02-14 2023-02-14 Fluorine-containing pyrazole phenylacetamide derivative and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202310109208.6A CN116003323B (en) 2023-02-14 2023-02-14 Fluorine-containing pyrazole phenylacetamide derivative and application thereof

Publications (2)

Publication Number Publication Date
CN116003323A CN116003323A (en) 2023-04-25
CN116003323B true CN116003323B (en) 2023-12-08

Family

ID=86026968

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202310109208.6A Active CN116003323B (en) 2023-02-14 2023-02-14 Fluorine-containing pyrazole phenylacetamide derivative and application thereof

Country Status (1)

Country Link
CN (1) CN116003323B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102803203A (en) * 2009-05-12 2012-11-28 罗马克实验室有限公司 Haloalkyl heteroaryl benzamide compounds
CN111187215A (en) * 2020-01-21 2020-05-22 西北农林科技大学 Fluorine-containing pyrazole amide derivatives, preparation method and application thereof
CN111592529A (en) * 2020-07-02 2020-08-28 安阳师范学院 Phenyl pyrazole amide derivative and preparation method and application thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102803203A (en) * 2009-05-12 2012-11-28 罗马克实验室有限公司 Haloalkyl heteroaryl benzamide compounds
CN111187215A (en) * 2020-01-21 2020-05-22 西北农林科技大学 Fluorine-containing pyrazole amide derivatives, preparation method and application thereof
CN111592529A (en) * 2020-07-02 2020-08-28 安阳师范学院 Phenyl pyrazole amide derivative and preparation method and application thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
STN Registry.《STN Registry》.2022,第1-6页. *

Also Published As

Publication number Publication date
CN116003323A (en) 2023-04-25

Similar Documents

Publication Publication Date Title
JP2004513163A (en) Pyrrolecarboxamides and pyrrolecarbothioamides and their pesticidal uses
CN112645897A (en) Thiazole derivative and preparation method and application thereof
CN105949181B (en) 4- hydroxypyrrole quinoline -2- ketone derivatives, preparation method and the application of the oxadiazoles containing 1,3,4-
CN110437146A (en) A kind of preparation of quinoline 4- hydroxy methacrylates class compound and its application in controlling plant diseases
JPH01313402A (en) Controller of gray mold comprising n-indanylcarboxylic acid amide catalyst as active ingredient
Li et al. Design, synthesis and structure–activity relationship of novel diphenylamine derivatives
CN105418504B (en) The pyrazolecarboxamide compounds of the base containing diaryl-amine and its application in agricultural chemicals
CN116003323B (en) Fluorine-containing pyrazole phenylacetamide derivative and application thereof
CN108314679B (en) Bactericide containing 1,3, 4-oxadiazole ring stilbene amide and preparation method and application thereof
CN105669559B (en) Pinanylpyrazoles and their synthetic methods and applications
CN102757400B (en) 2, 5-substituent group oxazole derivative and applications thereof
CN108440412B (en) A kind of 2-pyrazoleamide cyclohexane sulfonamide compound, preparation method and application thereof
CN106543139B (en) Triazolone compound and application thereof
CN105960401B (en) Pyridyl group or pyrimidyl compounds
CN109232550B (en) A kind of compound containing 3-chloro-5-trifluoromethylpyridyl-1,3,4-oxadiazol-2-one and application thereof
CN102617482B (en) Containing trifluoromethyl pyrimidine ammoniate, preparation method and the purposes as sterilant
CN114380767A (en) A kind of thiazole amide compound containing diphenylamine group and its preparation method and application
CN104003924B (en) N-substituted-3-[3-(substituted phenyl)-2-en-1-one]-4-hydroxypyrroline-2-one compound and its preparation method and application
CN110156685B (en) Aromatic cyclopentenopyridine, and synthesis method and application thereof
JPH0232249B2 (en) KOGAKUKATSUSEITORIAZORIRUARUKOORUJUDOTAIOJUKOSEIBUNTOSHITEGANJUSURUSATSUKINZAI
CN107056687B (en) Pyridine group-containing 1, 4-pentadiene-3-ketoxime ester compound, preparation method and application
CN108440510A (en) A kind of acid amide fungicides
CN115477619B (en) Triazole sulfonamide derivatives containing oxime ether fragments and their preparation methods and applications, and a fungicide and its applications
CN102020592B (en) Urea carbamate methyl substituted arly ester with bactericidal activity
CN102977079B (en) The pyrrolinone compounds of a kind of pyrazolyl containing group, preparation method and applications

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant