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

Fluorine-containing pyrazole phenylacetamide derivative and application thereof Download PDF

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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
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CN116003323A (en
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徐丹
王伟
黄家川
陆正仪
赵思颖
徐功
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Northwest A&F University
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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

Fluorine-containing pyrazole phenylacetamide derivative and application thereof
Technical Field
The application relates to the technical field of chemistry and pharmaceutical chemistry, in particular to a fluorine-containing pyrazole phenylacetamide derivative and application thereof.
Background
The pesticide is an important production data in the grain production process, and has an important effect on ensuring high and stable yield of agricultural crops. It is counted that plant pathogenic fungi infection results in a 20% decrease in crop yield worldwide each year and a 10% decrease after harvest, which not only brings great economic losses to farmers but also severely threatens the global food production safety. The application of bactericides is the most effective measure for preventing and curing plant pathogenic fungi at present, and a great amount of losses can be recovered each year. Among the many bactericides, the SDHIs type bactericides are widely used for their high-efficiency broad-spectrum antifungal activity, and their mechanism of action is: the protein complex II is acted on a respiratory chain electron transfer system of pathogenic bacteria to block energy metabolism and inhibit the growth of the pathogenic bacteria to cause death of the pathogenic bacteria, so that the aim of preventing diseases is fulfilled.
The most obvious feature of the SDHIs germicides in chemical structure is that the germicides contain amide groups, the newly developed germicides are formed by carrying out group substitution and derivatization on the basis of the prior germicides, from 1996 to 2022, 24 SDH inhibitors are marketed, wherein the ratio of pyrazole ring contained in the germicides is up to 54.17 percent (13/24); the broad-spectrum and high-efficiency antifungal activity of the bactericide is applied to fungal diseases of a plurality of crops, and the bactericide has become an important bactericide variety in production. However, due to excessive and unreasonable use, the resistance of fungi to such bactericides is becoming more severe. Therefore, the discovery of new targets or mechanisms of action to develop current bactericides is important to solve existing problems.
Disclosure of Invention
The application aims to solve the technical problems that: the application overcomes the defects in the prior art, and provides a fluorine-containing pyrazole phenylacetamide derivative and application thereof.
The technical scheme adopted for solving the technical problems is as follows: a fluorine-containing pyrazole phenylacetamide derivative has the following structural general formula:
wherein R is 1 Is trifluoromethyl or difluoromethyl; r is R 2 Methyl, methoxy, trifluoromethyl, fluoro or chloro, or substituted phenylacetyl is wholly replaced by 2-naphthylacetyl; r is R 3 Hydrogen, fluorine or chlorine.
The application of the fluorine-containing pyrazole phenylacetamide derivative in antifungal activity.
In addition, the fluorine-containing pyrazole phenylacetamide derivative can be used for preparing pesticide preparations for preventing and treating fungal plant diseases.
The beneficial effects of the application are as follows: the application has reasonable design and has the following advantages:
(1) The fluorine-containing pyrazole phenylacetamide derivative is used as a lead compound, and the target molecule is converted from a 'plane' shape to a 'non-plane' shape by prolonging a carbon chain of the compound, so that the combination of the target molecule and an active pocket has multiple combination modes, and the target molecule and the target protein can generate a new combination mode, thereby having novel structure, and being expected to expand a fungus prevention and treatment spectrum and overcome the problem of drug resistance which is serious day by day;
(2) The application discloses 50 fluorine-containing pyrazole phenylacetamide derivatives, provides chemical structures of the derivatives, and also verifies the antibacterial activity of the derivatives, and particularly: the fluorine-containing pyrazole phenylacetamide derivative with the concentration of 50mg/L is used for identifying the antibacterial activity of 4 fungi of sclerotinia rot of colza, canker of apple, wheat take-all and banded sclerotial blight of rice, and the result shows that most compounds have the inhibition effect on the 4 fungi.
Detailed Description
The application will now be described in further detail with reference to preferred embodiments.
Example 1 Compound 1
Compound 1 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-phenylacetamide having the formula:
compound 1 in this example was a yellow solid in 72% yield; melting point = 120.0-122.8 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 CNMR(101MHz,DMSO-d 6 )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 calculatedfor C 13 H 12 F 3 N 3 O[M+Na] + ,306.0825；found 306.0822.
example 2 Compound 2
Compound 2 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-o-tolylacetamide having the formula:
compound 2 in this example was a white solid in 81% yield; melting point = 143.3-145.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 C 14 H 14 F 3 N 3 O[M+Na] + ,320.0981；found 320.0983.
EXAMPLE 3 Compound 3
Compound 3 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-m-tolylacetamide having the formula:
compound 3 in this example was a yellow solid in 76% yield; melting point = 114.0-116.0 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 4 Compound 4
Compound 4 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-p-tolylacetamide having the formula:
compound 4 in this example was a yellow solid in 75% yield; melting point = 128.8-131.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 for C 14 H 14 F 3 N 3 O[M+Na] + ,320.0981；found 320.0981.
EXAMPLE 5 Compound 5
Compound 5 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (2-methoxyphenyl) acetamide, which has the following chemical formula:
compound 5 in this example was a white solid with a yield of 62%; melting point = 104.0-107.8 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 6 Compound 6
Compound 6 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (3-methoxyphenyl) acetamide, which has the following chemical formula:
compound 6 in this example was a yellow solid in 80% yield; melting point = 108.8-112.5 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 7 Compound 7
Compound 7 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (4-methoxyphenyl) acetamide, which has the following chemical formula:
compound 7 in this example was a yellow solid in 69% yield; melting point = 119.2-121.0 ℃; 1 H 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)； 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；found 336.0931.
EXAMPLE 8 Compound 8
Compound 8 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (2-fluorophenyl) acetamide having the formula:
compound 8 in this example was a white solid in 88% yield; melting point = 153.7-155.8 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 CNMR(101MHz,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.
EXAMPLE 9 Compound 9
Compound 9 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (3-fluorophenyl) acetamide having the formula:
compound 9 in this example was a yellow solid in 76% yield; melting point = 131.6-133.8 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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-MS calculated for C 13 H 11 F 4 N 4 O[M+Na] + ,324.0731；found 324.0728.
example 10 Compound 10
Compound 10 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (4-fluorophenyl) acetamide having the formula:
compound 10 in this example was a yellow solid in 74% yield; melting point = 132.6-134.5 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 CNMR(101MHz,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 for C 13 H 11 F 4 N 4 O[M+Na] + ,324.0731；found 324.0725.
EXAMPLE 11 Compound 11
Compound 11 is 2- (2-chlorophenyl) -N- (3-trifluoromethyl) -1-methyl-1H-pyrazol-5-ylacetamide having the formula:
compound 11 in this example was a yellow solid in 86% yield; melting point = 163.5-165.1 ℃; 1 H 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)； 13 C 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-MS calculated for C 13 H 11 ClF 3 N 3 O[M+Na] + ,340.0435；found 340.0435.
EXAMPLE 12 Compound 12
Compound 12 is 2- (3-chlorophenyl) -N- (3-trifluoromethyl) -1-methylpyrazole-5-acetamide having the formula:
compound 12 in this example was a white solid in 82% yield; melting point = 127.1-130.9 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.48(s,1H),7.42–7.34(m,4H),6.65(s,1H),3.77(s,5H)； 13 C NMR(101MHz,DMSO-d 6 )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 for C 13 H 11 ClF 3 N 3 O[M+Na] + ,340.0435；found 340.0435.
EXAMPLE 13 Compound 13
Compound 13 is 2- (4-chlorophenyl) -N- (3-trifluoromethyl) -1-methyl-1H-pyrazol-5-ylacetamide having the formula:
compound 13 in this example was a yellow solid, 83% yield; melting point = 157.3-159.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.5(s,1H),7.4(q,J＝8.5Hz,4H),6.7(s,1H),3.8(s,5H)； 13 C NMR(101MHz,DMSO-d 6 )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 C 13 H 11 ClF 3 N 3 O[M+Na] + ,340.0435；found 340.0434.
EXAMPLE 14 Compound 14
Compound 14 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (2-trifluoromethylphenyl) acetamide having the formula:
compound 14 in this example was a yellow solid in 77% yield; melting point = 173.3-174.9 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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-MS calculated for C 14 H 11 F 6 N 3 O[M+Na] + ,374.0699；found 374.0697.
EXAMPLE 15 Compound 15
Compound 15 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (3-trifluoromethylphenyl) acetamide having the formula:
compound 15 in this example was a white solid in 75% yield; melting point = 166.8-170.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 16 Compound 16
Compound 16 is N- (3-trifluoromethyl) -1-methylpyrazol-5-yl-2- (4-trifluoromethylphenyl) acetamide having the formula:
compound 16 in this example was a yellow solid in 71% yield; melting point = 138.1-141.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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),97.3,41.8,36.9；ESI-MS calculated for C 14 H 11 F 6 N 3 O[M+Na] + ,374.0699；found 374.0697.
EXAMPLE 17 Compound 17
Compound 17 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2-phenylacetamide having the formula:
compound 17 in this example was a yellow solid in 82% yield; melting point = 92.6-93.0 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 calculated for C 13 H 13 F 2 N 3 O[M+Na] + ,288.0919；found 288.0920.
EXAMPLE 18 Compound 18
Compound 18 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2-o-tolylacetamide having the formula:
compound 18 in this example was a yellow solid in 85% yield; melting point = 164.5-165.9 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 CNMR(101MHz,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.
EXAMPLE 19 Compound 19
Compound 19 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2-m-tolylacetamide having the formula:
compound 19 in this example was a white solid in 66% yield; melting point = 122.5-124.6 ℃; 1 H 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)； 13 C 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 C 14 H 15 F 2 N 3 O[M+Na] + ,302.1075；found302.1069.
EXAMPLE 20 Compound 20
Compound 20 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2-p-tolylacetamide having the formula:
compound 20 in this example was a yellow solid in 71% yield; melting point = 160.1-162.0 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 C 14 H 15 F 2 N 3 O[M+Na] + ,302.1075；found 302.1072.
EXAMPLE 21 Compound 21
Compound 21 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (2-methoxyphenyl) acetamide having the formula:
compound 21 in this example was a yellow solid in 87% yield; melting point = 103.5-105.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 22 Compound 22
Compound 22 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (3-methoxyphenyl) acetamide, which has the formula:
compound 22 in this example was a white solid in 65% yield; melting point = 100.1-103.2 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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；found 318.1022.
EXAMPLE 23 Compound 23
Compound 23 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (4-methoxyphenyl) acetamide having the formula:
compound 23 in this example was a yellow solid in 75% yield; melting point = 99.9-102.4 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 C 14 H 15 F 2 N 3 O 2 [M+Na] + ,318.1025；found 318.1022.
EXAMPLE 24 Compound 24
Compound 24 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (2-fluorophenyl) acetamide having the formula:
compound 24 in this example was a yellow solid in 82% yield; melting point = 119.5-122.5 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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；found 306.0820.
EXAMPLE 25 Compound 25
Compound 25 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (3-fluorophenyl) acetamide having the formula:
compound 25 in this example was a white solid in 84% yield; melting point = 110.8-112.2 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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；found 306.0821.
EXAMPLE 26 Compound 26
Compound 26 is N- (3-difluoromethyl) -1-methyl-1H-pyrazol-5-yl-2- (4-fluorophenyl) acetamide having the formula:
compound 26 in this example was a yellow solid in 72% yield; melting point = 129.9-131.0 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 27 Compound 27
Compound 27 is 2- (2-chlorophenyl) -N- (3-difluoromethyl) -1-methyl-1H-pyrazol-5-ylacetamide having the formula:
compound 27 in this example was a yellow solid in 69% yield; melting point = 146.5-148.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 28 Compound 28
Compound 28 is 2- (3-chlorophenyl) -N- (3-difluoromethyl) -1-methyl-1H-pyrazol-5-ylacetamide having the formula:
compound 28 in this example was a white solid in 77% yield; melting point = 134.9-137.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
example 29 Compound 29
Compound 29 is 2- (4-chlorophenyl) -N- (3-difluoromethyl) -1-methyl-1H-pyrazol-5-yl) acetamide having the formula:
compound 29 in this example was a yellow solid in 75% yield; melting point = 146.5-148.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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-MS calculated for C 13 H 12 ClF 2 N 3 O[M+Na] + ,322.0529；found 322.0530.
EXAMPLE 30 Compound 30
Compound 30 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (2-trifluoromethylphenyl) acetamide having the formula:
compound 30 in this example was a yellow solid in 66% yield; melting point = 171.4-173.4 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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 for C 14 H 12 F 5 N 3 O[M+Na] + ,356.0793；found 356.0792.
EXAMPLE 31 Compound 31
Compound 31 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (3-trifluoromethylphenyl) acetamide having the formula:
compound 31 in this example was a white solid in 63% yield; melting point = 145.2-146.3 ℃; 1 H 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)； 13 C NMR(101MHz,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 for C 14 H 12 F 5 N 3 O[M+Na] + ,356.0793；found 356.0793.
EXAMPLE 32 Compound 32
Compound 32 is N- (3-difluoromethyl) -1-methylpyrazol-5-yl-2- (4-trifluoromethylphenyl) acetamide having the formula:
compound 32 in this example was a yellow solid in 67% yield; melting point = 136.4-138.0 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 33 Compound 33
Compound 33 is 2, 4-dichlorophenyl-N-1-methyl-3-trifluoromethylpyrazole-5-acetamide having the formula:
compound 33 in this example was a white solid in 75% yield; melting point = 192.1-195.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 34 Compound 34
Compound 34 is 2- (3, 4-dichlorophenyl) -N- (1-methyl-3-trifluoromethyl) -1H-pyrazol-5-ylacetamide having the following formula:
compound 34 in this example was a white solid in 72% yield; melting point = 197.6-198.9 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.49(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(101MHz,DMSO-d 6 )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 calculated for C 13 H 11 Cl 2 F 3 N 3 O[M+H] + ,352.0226；found 352.0226.
EXAMPLE 35 Compound 35
Compound 35 is 2- (3, 5-dichlorophenyl) -N- (1-methyl-3-trifluoromethyl) pyrazole-5-acetamide having the formula:
compound 35 in this example was a white solid in 79% yield; melting point = 190.2-193.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.51(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(101MHz,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-MS calculated for C 13 H 11 Cl 2 F 3 N 3 O[M+H] + ,352.0226；found 352.0222.
EXAMPLE 36 Compound 36
Compound 36 is 2- (2, 4-bistrifluoromethyl) phenyl-N- (1-methyl-3-trifluoromethyl) pyrazole-5-acetamide having the formula:
compound 36 in this example was a white solid in 61% yield; melting point = 168.2-170.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )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). 13 C NMR(101MHz,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 for C 15 H 11 F 9 N 3 O[M+H] + ,420.0753；found 420.0754.
EXAMPLE 37 Compound 37
Compound 37 is 2- (3, 5-bistrifluoromethylphenyl) -N- (1-methyl-3-trifluoromethyl) pyrazole-5-acetamide having the formula:
compound 37 in this example was a white solid in 65% yield; melting point = 186.0-188.4 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.60(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(101MHz,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.
EXAMPLE 38 Compound 38
Compound 38 is N-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-naphtylacetamide having the formula:
compound 38 in this example was a white solid in 65% yield; melting point = 186.4-187.7 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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.
EXAMPLE 39 Compound 39
Compound 39 is N- (4-chloro-1-methyl-3-trifluoromethyl) -1H-pyrazol-5-yl-2- (3-chlorophenyl) acetamide having the formula:
compound 39 in this example was a white solid in 81% yield; melting point = 167.1-170.2 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.77(s,1H),7.45(s,1H),7.33(s,3H),3.81(s,2H),3.70(s,3H)； 13 C NMR(101MHz,DMSO-d 6 )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 for C 13 H 9 Cl 2 F 3 N 3 O[M-H] - ,350.0080；found 350.0070.
EXAMPLE 40 Compound 40
Compound 40 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2- (4-chlorophenyl) acetamide having the formula:
compound 40 in this example was a yellow solid in 79% yield; melting point = 181.3-183.0 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.63(s,1H),7.44–7.36(m,4H),3.78(s,2H),3.69(s,3H)； 13 C NMR(101MHz,DMSO-d 6 )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 C 13 H 9 Cl 2 F 3 N 3 O[M-H] - ,350.0080；found 350.0070.
EXAMPLE 41 Compound 41
Compound 41 is 2- (3-chlorophenyl) -N- (4-fluoro-1-methyl-3-trifluoromethyl) -1H-pyrazol-5-ylacetamide having the following formula:
compound 41 in this example was a yellow solid in 82% yield; melting point = 119.6-121.0 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.43(s,1H),7.36(ddd,J＝28.2,16.5,8.4Hz,4H),3.80(s,2H),3.68(s,3H)； 13 C NMR(101MHz,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[M-H] - ,334.0376；found334.0368.
EXAMPLE 42 Compound 42
Compound 42 is 2- (4-chlorophenyl) -N- (4-fluoro-1-methyl-3-trifluoromethyl) -1H-pyrazol-5-ylacetamide having the following formula:
compound 42 in this example was a yellow solid in 85% yield; melting point = 133.5-136.2 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.51(s,1H),7.40(s,4H),3.78(s,2H),3.67(s,3H). 13 C NMR(101MHz,DMSO-d 6 )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-MS calculated for C 13 H 9 ClF 4 N 3 O[M-H] - ,334.0376；found 334.0368.
EXAMPLE 43 Compound 43
Compound 43 is N- (4-chloro-1-methyl-3-trifluoromethyl) pyrazol-5-yl-2- (3 (trifluoromethyl) phenyl) acetamide having the formula:
compound 43 in this example was a white solid in 65% yield; melting point = 161.2-163.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.56(s,1H),7.74(s,1H),7.69–7.57(m,3H),3.92(s,2H),3.71(s,3H)； 13 C NMR(101MHz,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[M-H] - ,384.0344；found 384.0335.
EXAMPLE 44 Compound 44
Compound 44 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2- (4 (trifluoromethyl) phenyl) acetamide having the formula:
compound 44 in this example was a yellow solid in 62% yield; melting point = 174.2-175.5 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.57(s,1H),7.72(d,J＝8.1Hz,2H),7.59(s,2H),3.90(s,2H),3.70(s,3H)； 13 C NMR(101MHz,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[M-H] - ,384.0344；found384.0334.,37.8；ESI-MS calculated for C 14 H 9 ClF 6 N 3 O[M-H] - ,384.0344；found 384.0334.
EXAMPLE 45 Compound 45
Compound 45 is N- (4-fluoro-1-methyl-3-trifluoromethyl) -1H-pyrazol-5-yl-2- (3-trifluoromethylphenyl) acetamide having the formula:
compound 45 in this example was a yellow solid in 71% yield; melting point = 172.5-173.6 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 CNMR(101MHz,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[M-H] - ,368.0639；found 368.0628.
EXAMPLE 46 Compound 46
Compound 46 is N- (4-fluoro-1-methyl-3-trifluoromethyl) -1H-pyrazol-5-yl-2- (4-trifluoromethylphenyl) acetamide having the formula:
compound 46 in this example was a white solid in 66% yield; melting point = 169.2-172.1 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ10.50(s,1H),7.72(d,J＝8.0Hz,2H),7.59(s,2H),3.90(s,2H),3.69(s,3H)； 13 C NMR(101MHz,DMSO-d 6 )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-MS calculated for C 14 H 9 F 7 N 3 O[M-H] - ,368.0639；found 368.0625.
EXAMPLE 47 Compound 47
Compound 47 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-m-tolylacetamide having the following formula:
compound 47 in this example was a yellow solid in 81% yield; melting point = 106.2-108.5 ℃; 1 H 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)； 13 C 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 C 14 H 12 ClF 3 N 3 O[M-H] - ,330.0626；found 330.0618.
EXAMPLE 48 Compound 48
Compound 48 is N-chloro-1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl-2-p-tolylacetamide having the formula:
compound 48 in this example was a yellow solid in 76% yield; melting point = 147.2-150.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 for C 14 H 12 ClF 3 N 3 O[M-H] - ,330.0626；found 330.0617. 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,DMSO-d 6 )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 for C 14 H 12 ClF 3 N 3 O[M-H] - ,330.0626；found 330.0617.
EXAMPLE 49 Compound 49
Compound 49 is N- (4-fluoro-1-methyl-3-trifluoromethyl) -1H-pyrazol-5-yl-2-m-tolylacetamide having the following formula:
compound 49 in this example was a white solid in 85% yield; melting point = 101.0-103.5 ℃; 1 H 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)； 13 CNMR(101MHz,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[M-H] - ,314.0922；found 314.0913.
EXAMPLE 50 Compound 50
Compound 50 is N- (4-fluoro-1-methyl-3-trifluoromethyl) -1H-pyrazol-5-yl-2-p-tolylacetamide having the following formula:
compound 50 in this example was a yellow solid in 77% yield; melting point = 126.2-128.3 ℃; 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(101MHz,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 for C 14 H 12 F 4 N 3 O[M-H] - ,314.0922；found 314.0913.
inhibition of test phytopathogenic fungi by the fluorine-containing pyrazole phenylacetamide derivatives (Compound No. 1 to 50) synthesized in examples 1 to 50.
1. Experimental objects
Fluorine-containing pyrazole phenylacetamide derivatives synthesized in examples 1 to 50
2. Experimental method
The in vitro inhibition activity of the compounds 1 to 50 on the plant pathogenic fungi to be tested at a concentration of 50mg/L was determined by using a hypha linear growth rate method. The selected fungi are provided by the institute of agrochemicals at the university of agriculture and forestry science and technology in northwest.
Taking 50mg/L of fluxapyroxad solution as a positive control, taking 5% of DMSO aqueous solution as a blank control, completely dissolving an accurately weighed compound to be tested in 5% of DMSO (v/v) aqueous solution, and rapidly and uniformly mixing 10mL of solution to be tested or control solution with 90mL of sterile PDA culture medium at 50 ℃ to obtain a liquid medicine with the mass concentration of 25 mg/L; it was poured hot into sterilized petri dishes, 10mL each, and cooled for use. Inoculating plant pathogenic fungi to be tested (bacterial cake diameter 5 mm) into the culture dish, wherein each test group is provided with 3 parallel groups; after culturing it in a constant temperature incubator at 25℃for 72 hours, colony diameter (mm) was measured by the crisscross method, and the hypha growth Inhibition Ratio (IR) was calculated according to the formula (1): IR (%) = [ (d) c -d 0 )-(ds-d 0 )]/(d c -d 0 )×100(1)；
Wherein: d, d 0 Diameter of the bacterial cake (5 mm), d c The average diameter (mm) of the colonies of the blank group, and ds is the average diameter (mm) of the colonies of the sample group.
3. The experimental results are shown in Table 1
TABLE 1 in vitro bacteriostatic Activity of the Synthesis of fluorine-containing pyrazole phenylacetamide derivatives in examples 1 to 50 a (inhibition ratio,%) (50 mg/L)
a The data in the table are the average of three times of data; s.s. b S.sclerotiorum；V.m. d V.mali；G.g f G.graminis；R.s g R.solani
As can be seen from Table 1, at a concentration of 50mg/L, the activity of Compound 42 against Rhizoctonia cerealis was most excellent, the inhibition rate thereof was as high as 100%, the inhibition rate of Compound 16 against Rhizoctonia cerealis was 91.3%, the activity of Compound 42 against Malus mali was most excellent, the inhibition rate thereof was 86.9%, and the inhibition rate of Compound 49 against Rhizoctonia cerealis was 92.8%.
In summary, 50 fluorine-containing pyrazole phenylacetamide derivatives prepared by chemical synthesis have antifungal activity, particularly have remarkable antibacterial activity on wheat take-all germs and rice sheath blight germs, and lay a foundation for preparing bactericides with the fluorine-containing pyrazole phenylacetamide derivatives as main antifungal active ingredients.
The foregoing description is merely illustrative of specific embodiments of the application, and the application is not limited to the details shown, since modifications and variations of the foregoing embodiments may be made by those skilled in the art without departing from the spirit and scope of the application.

Claims (2)

1. A fluorine-containing pyrazole phenylacetamide derivative, which is characterized in that: the fluorine-containing pyrazole phenylacetamide derivative is selected from the following compounds:
2. use of a fluorine-containing pyrazole phenylacetamide derivative according to claim 1, characterized in that: the application of the fluorine-containing pyrazole phenylacetamide derivative in the aspect of antifungal activity.
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Citations (3)

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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 derivative, 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

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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 derivative, 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

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