Pest control composition including novel iminopyridine derivative

Abstract

Provided is a pest control composition containing a novel iminopyridine derivative and other pest control agents. Provided is a pest control composition containing an iminopyridine derivative represented by the following Formula (I) and at least one of other pest control agents: ##STR00001## [in the formula (I), Ar represents a 5- to 6-membered heterocycle which may be substituted, A represents a heterocycle having a 5- to 10-membered unsaturated bond including one or more nitrogen atoms, and has an imino group substituted with an R group at a position adjacent to the nitrogen atom present on the cycle, Y represents hydrogen, halogen and the like, and R represents any one of groups represented by the following Formulae (a) to (e), (y) or (z)]. ##STR00002##

Claims

1. A pest control composition comprising: at least one iminopyridine derivative selected from the group consisting of N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide and acid addition salts thereof; and at least one insecticide selected from the group consisting of chlorantraniliprole, afidopyropen, and agriculturally and/or zootechnically acceptable acid addition salts thereof: wherein the at least one iminopyridine derivative:the at least one insecticide is in a range from 0.1 to 80% by weight: 0.1 to 80% by weight.

2. A method for protecting plants or animals from pests comprising simultaneously or independently applying the pest control composition of claim 1 to a region to be treated.

3. A method for protecting plants or animals from pests by treating pests, plants, seeds of plants, soil, cultivation carriers or animals as a target, with an effective amount of the pest control composition of claim 1.

4. pest control composition comprising: at least one iminopyridine derivative selected from the group consisting of N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide and acid addition salts thereof; and at least one other pest control agent, wherein the other pest control agent is a control agent for animal parasitic pests and is selected from the group consisting of chlorantraniliprole, afidopyropen, and agriculturally and/or zootechnically acceptable acid addition salts thereof; wherein the at least one iminopyridine derivative: the control agent for animal parasitic pests is in a range from 0.1 to 80% by weight: 0.1 to 80% by weight.

5. The pest control composition according to claim 1, wherein the pest is at least one selected from the group consisting of Frankliniella occidentalis, Laodelphax striatella, Aphis gossypii, Plutella xylostella; Spodoptera litura, Chilo suppressalis, Callosobruchus chinensis and Haemaphysalis longicornis.

6. The pest control composition according to claim 4, wherein the pest is at least one selected from the group consisting of Frankliniella occidentalis, Laodelphax striatella, Aphis gossypii, Plutella xylostella; Spodoptera litura, Chilo suppressalis, Callosobruchus chinensis and Haemaphysalis longicornis.

7. A method for protecting plants or animals from pests according to claim 2, wherein the pest is at least one selected from the group consisting of Frankliniella occidentalis, Laodelphax striatella, Aphis gossypii, Plutella xylostella; Spodoptera litura, Chilo suppressalis, Callosobruchus chinensis and Haemaphysalis longicornis.

8. A method for protecting plants or animals from pests according to claim 3, wherein the pest is at least one selected from the group consisting of Frankliniella occidentalis, Laodelphax striatella, Aphis gossypii, Plutella xylostella; Spodoptera litura, Chilo suppressalis, Callosobruchus chinensis and Haemaphysalis longicornis.

Description

EXAMPLES

(1) Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the Examples.

Synthetic Example P1

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (Compound P212)

(2) (1) 25 g (270 mmol) of 2-aminopyridine was dissolved in 200 ml of anhydrous dichloromethane, 41 ml (30 g, 300 mmol) of triethylamine was added thereto, and the mixture was cooled to 0 C. 38 ml (57 g, 270 mmol) of anhydrous trifluoroacetic acid was added dropwise thereto over 15 minutes, and the resulting mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was injected into about 100 ml of iced water, and the mixture was stirred for 10 minutes. The mixture was transferred to a separatory funnel to perform liquid separation, and the organic layer was washed twice with 150 ml of water and twice with 150 ml of a 1% HCl aqueous solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 36 g (yield 71%) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide.

(3) 1H-NMR (CDCl3, , ppm): 7.20 (1H, ddd), 7.83 (1H, td), 8.20 (1H, d), 8.35 (1H, d), 10.37 (1H, brs)

(4) 13C-NMR (CDCl3, , ppm): 115.3, 115.5 (q), 121.6, 139.1, 147.9, 149.5, 155.3 (q)

(5) MS: m/z=191 (M+H)

(6) (2) 20 g (126 mmol) of 2-chloro-5-chloromethyl pyridine was dissolved in 200 ml of anhydrous acetonitrile, 24 g (126 mmol) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide obtained by the above-described method and 21 g (151 mmol) of potassium carbonate were added thereto, and the resulting mixture was heated and refluxed for 6 hours, and then stirred at room temperature for 10 hours. After the reaction was completed, the reaction solution was filtered and the liquid was concentrated under reduced pressure. Diethyl ether was added thereto for crystallization, and the crystals thus obtained were collected and washed well with diethyl ether and water. The crystals thus obtained were dried under reduced pressure at 60 C. for 1 hour to obtain the subject material. Amount obtained 26 g (yield 66%).

(7) 1H-NMR (CDCl3, , ppm): 5.57 (2H, s), 6.92 (1H, td), 7.31 (1H, d), 7.80 (1H, td), 7.87 (1H, dd), 7.99 (1H, dd), 8.48 (2H, m)

(8) 13C-NMR (CDCl3, , ppm): 53.8, 115.5, 117.2 (q), 122.1, 124.7, 130.0, 139.2, 140.0, 142.5, 149.7, 151.8, 158.9, 163.5 (q)

(9) MS: m/z=316 (M+H)

(10) (3) Powder X-ray crystal analysis

(11) In the powder X-ray diffraction, measurement was performed under the following conditions.

(12) Device name: RINT-2200 (Rigaku Corporation)

(13) X-ray: Cu-K (40 kV, 20 mA)

(14) Scanning range: 4 to 40, sampling width: 0.02 and scanning rate: 1/min

(15) The results are as follows.

(16) Diffraction angle (2) 8.7, 14.2, 17.5, 18.3, 19.80, 22.40, 30.9 and 35.3

(17) (4) Differential Scanning Calorimetry (DSC)

(18) In the differential scanning calorimetry, measurement was performed under the following conditions.

(19) Device name: DSC-60

(20) Sample cell: aluminum

(21) Temperature range: 50 C. to 250 C. (heating rate: 10 C./min)

(22) As a result, the melting point was observed at 155 C. to 158 C.

(23) Another Method of Synthetic Example P1

(24) 3.00 g (18.6 mmol) of 2-chloro-5-chloromethyl pyridine was dissolved in 20 ml of anhydrous DMF, 1.75 g (18.6 mmol) of 2-aminopyridine was added thereto, and the resulting mixture was stirred at 80 C. for 8 hours and at room temperature for 5 hours. After the reaction was completed, DMF was distilled off under reduced pressure, acetonitrile was added thereto to precipitate a solid, and the solid was collected, washed well with acetonitrile and dried to obtain 2.07 g (yield 44%) of 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride.

(25) 1H-NMR (DMSO-d6, , ppm): 5.65 (2H, s), 6.96 (1H, t), 7.23 (1H, m), 7.57 (1H, d), 7.80 (1H, m), 7.91 (1H, m), 8.28 (1H, m), 8.49 (1H, d), 9.13 (2H, brs)

(26) 50 mg (0.20 mmol) of the 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride obtained by the above-described method was dissolved in 5 ml of anhydrous dichloromethane, 122 mg (1.00 mmol) of DMAP and 50 mg (0.24 mmol) of anhydrous trifluoroacetic acid were added thereto in sequence under ice cold conditions, and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed with 1% hydrochloric acid, and then dried over anhydrous magnesium sulfate. Dichloromethane was distilled off under reduced pressure to obtain the subject material. Amount obtained 42 mg (yield 67%). NMR was the same as that of the above-described method.

Synthetic Example P2

2,2-dibromo-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-acetamide (Compound P241)

(27) 200 mg (0.78 mmol) of the 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride obtained by the method described in another method of Synthetic Example P1, 238 mg (1.95 mmol) of DMAP and 224 mg (1.17 mmol) of EDC-HCl were dissolved in 10 ml of anhydrous dichloromethane, 101 l (202 mg, 1.17 mmol) of dibromoacetic acid was added thereto, and the resulting mixture was stirred at room temperature overnight. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed once with water and twice with a 1% HCl aqueous solution, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the subject material. Amount obtained 50 mg (yield 15%)

(28) 1H-NMR (CDCl3, , ppm): 5.56 (2H, s), 5.99 (1H, s), 6.78 (1H, td), 7.33 (1H, d), 7.69 (1H, td), 7.76 (1H, dd), 7.93 (1H, dd), 8.39 (1H, d), 8.50 (1H, d)

(29) 13C-NMR (CDCl3, , ppm): 44.6, 53.1, 113.7, 121.9, 124.8, 130.1, 138.2, 139.7, 141.2, 149.5, 152.0, 159.4, 172.2

(30) MS: m/z=418 (M+H)

Synthetic Example P3

N-[1-((6-chloro-5-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (Compound P227)

(31) 4.00 g (27.6 mmol) of 2-chloro-3-fluoro-5-methyl pyridine was dissolved in 80 ml of carbon tetrachloride, 7.37 g (41.4 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added thereto, and the resulting mixture was heated and refluxed overnight. After the reaction was completed, the reaction solution was returned to room temperature, concentrated under reduced pressure and purified by silica gel column chromatography (hexane:ethyl acetate=19:1) to obtain 3.06 q (yield 51%) of 5-(bromomethyl)-2-chloro-3-fluoropyridine.

(32) 1H-NMR (CDCl3, , ppm): 4.45 (2H, s), 7.54 (1H, dd), 8.23 (1H, s)

(33) 50 mg (0.22 mmol) of the 5-(bromomethyl)-2-chloro-3-fluoropyridine obtained by the aforementioned method was dissolved in 5 ml of anhydrous acetonitrile, 42 mg (0.22 mmol) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetoamide obtained by the method described in (1) of Reference Example 1 and 36 mg (0.26 mmol) of potassium carbonate were added thereto in sequence, and the resulting mixture was heated and refluxed for 7 hours. After the reaction was completed, the reaction solution was returned to room temperature to filter insoluble materials, and the filtrate was concentrated under reduced pressure. Diethyl ether was added thereto to precipitate a solid, and thus the solid was collected, washed with diethyl ether, and then dried under reduced pressure in a desiccator to obtain the subject material. Amount obtained 29 mg (yield 40%).

(34) 1H-NMR (CDCl3, , ppm): 5.54 (2H, s), 6.89 (1H, td), 7.76 (1H, dd), 7.80 (1H, td), 7.85 (1H, d), 8.29 (1H, d), 8.57 (1H, d)

(35) MS: m/z=334 (M+H)

Synthetic Example P4

N-[1-((6-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (Compound P229)

(36) 500 mg (4.50 mmol) of 2-fluoro-5-methyl pyridine was dissolved in 50 ml of carbon tetrachloride, 1.20 g (6.76 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added thereto, and the resulting mixture was heated and refluxed for 2.5 hours. After the reaction was completed, the reaction solution was returned to room temperature, and the solvent was distilled off under reduced pressure and purified by silica gel column chromatography (hexane:ethyl acetate=19:1) to obtain 300 mg (yield 35%) of 5-bromomethyl-2-fluoropyridine.

(37) 57 mg (0.30 mmol) of the 5-bromomethyl-2-fluoropyridine obtained by the aforementioned method was dissolved in 10 ml of anhydrous acetonitrile, 57 mg (0.30 mmol) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetoamide synthesized by the method described in (1) of Synthetic Example P1 and 69 mg (0.50 mmol) of potassium carbonate were added thereto in sequence, and the resulting mixture was heated and refluxed for 6 hours. After the reaction was completed, the reaction solution was returned to room temperature to filter insoluble materials, and the filtrate was concentrated under reduced pressure. The filtrate was purified by silica gel column chromatography (hexane:ethyl acetate=1:1.fwdarw.3:1) to obtain the subject material. Amount obtained 21 mg (yield 23%).

(38) 1H-NMR (CDCl3, , ppm): 5.56 (2H, s), 6.89 (1H, td), 6.94 (1H, d), 7.79 (1H, td), 7.87 (1H, d), 8.03 (1H, m), 8.31 (1H, s), 8.54 (1H, d)

(39) MS: m/z=300 (M+H)

Synthetic Example P5

N-[1-((6-bromopyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (Compound P231)

(40) 500 mg (2.92 mmol) of 2-bromo-5-methylpyridine was dissolved in 15 ml of carbon tetrachloride, 623 mg (3.50 mmol) of N-bromosuccinimide and 10 mg of benzoyl peroxide were added thereto, and the resulting mixture was heated and refluxed for 19 hours. After the reaction was completed, the reaction solution was returned to room temperature, concentrated under reduced pressure and purified by silica gel column chromatography (hexane:ethyl acetate=19:1) to obtain 143 mg (yield 20%) of 2-bromo-5-bromomethylpyridine.

(41) 1H-NMR (CDCl3, , ppm): 4.42 (2H, s), 7.47 (1H, d), 7.59 (1H, dd), 8.38 (1H, d)

(42) 70 mg (0.28 mmol) of the 2-bromo-5-bromomethylpyridine obtained by the aforementioned method was dissolved in 10 ml of anhydrous acetonitrile, 54 mg (0.28 mmol) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetoamide synthesized by the method described in (1) of Synthetic Example P1 and 46 mg (0.34 mmol) of potassium carbonate were added thereto in sequence, and the resulting mixture was heated and refluxed for 6 hours. After the reaction was completed, the reaction solution was returned to room temperature to filter insoluble materials, and the filtrate was concentrated under reduced pressure. Diethyl ether was added thereto to precipitate a solid, and thus the solid was collected, washed with diethyl ether, and then dried under reduced pressure in a desiccator to obtain the subject material. Amount obtained 81 mg (yield 82%).

(43) 1H-NMR (CDCl3, , ppm): 5.52 (2H, s), 6.8 (1H, t), 7.48 (1H, d), 7.78 (2H, m), 7.84 (1H, d), 8.44 (1H, d), 8.53 (1H, d)

(44) MS: m/z=360 (M+H)

Synthetic Example P6

2-chloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-acetamide (Compound P236)

(45) 70 mg (0.27 mmol) of the 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride obtained by the method described in another method of Synthetic Example P1 was dissolved in 4 ml of anhydrous dichloromethane, 82 mg (0.67 mmol) of DMAP, 25 mg (0.27 mmol) of chloroacetic acid and 62 mg (0.32 mmol) of EDC-HCl were added thereto in sequence, and the resulting mixture was stirred at room temperature overnight. After the reaction was completed, dichloromethane was added thereto to dilute the mixture, and the mixture was washed with water and a 1% HCl aqueous solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain the subject material. Amount obtained 4 mg (yield 5%).

(46) 1H-NMR (CDCl3, , ppm): 4.17 (2H, s), 5.46 (2H, s), 6.64 (1H, td), 7.31 (1H, d), 7.60 (1H, td), 7.64 (1H, dd), 7.80 (1H, dd), 8.32 (1H, d), 8.45 (1H, d)

(47) MS: m/z=296 (M+H)

Synthetic Example P7

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide (Compound P238)

(48) 400 mg (4.26 mmol) of 2-aminopyridine was dissolved in 10 ml of anhydrous dichloromethane, 322 l (490 mg, 5.11 mmol) of difluoroacetic acid, 982 mg (5.10 mmol) of EDC-HCl and 622 mg (5.11 mmol) of DMAP were added thereto, and the resulting mixture was stirred at room temperature for 61 hours. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed once with water and twice with a 1% HCl aqueous solution, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 102 mg (yield 14%) of 2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide.

(49) 1H-NMR (CDCl3, , ppm): 6.03 (1H, t), 7.15 (1H, m), 7.78 (1H, td), 8.20 (1H, d), 8.34 (1H, dd), 8.72 (1H, brs)

(50) 100 mg (0.58 mmol) of the 2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide obtained by the aforementioned method was dissolved in 10 ml of anhydrous acetonitrile, 94 mg (0.58 mmol) of 2-chloro-5-chloromethyl pyridine was dissolved in 5 ml of anhydrous acetonitrile and added thereto, and subsequently, 84 mg (0.63 mmol) of potassium carbonate was added thereto and the resulting mixture was heated and refluxed for 140 minutes. After the reaction was completed, the reaction solution was returned to room temperature to filter off insoluble materials, and the filtrate was concentrated under reduced pressure. Ether was added thereto to precipitate a solid, and thus the solid was collected and dried well to obtain the subject material. Amount obtained 63 mg (yield 37%).

(51) 1H-NMR (CDCl3, , ppm): 5.52 (2H, s), 5.90 (1H, t), 6.79 (1H, td), 7.33 (1H, d), 7.71 (1H, m), 7.77 (1H, dd), 7.85 (1H, dd), 8.45 (1H, d), 8.50 (1H, d)

(52) 13C-NMR (DMSO-d6, , ppm): 53.0, 111.0 (t), 115.2, 120.7, 124.7, 131.7, 140.6, 141.6, 143.2, 150.4, 150.9, 158.3, 169.4 (t)

(53) MS: m/z=298 (M+H)

Synthetic Example P8

2-chloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2-difluoroacetamide (Compound P239)

(54) 200 mg (2.13 mmol) of 2-aminopyridine was dissolved in 5 ml of dichloromethane, 491 mg (2.55 mmol) of EDC-HCl, 311 mg (2.55 mmol) of DMAP and 187 l (2.23 mmol, 290 mg) of chlorodifluoroacetic acid were added thereto in sequence, and the resulting mixture was stirred overnight. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed with water and 1% hydrochloric acid, and then dried over anhydrous magnesium sulfate to obtain 105 mg (yield 24%) of 2-chloro-2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide.

(55) 1H-NMR (CDCl3, , ppm): 7.19 (1H, dd), 7.82 (11H, m), 8.18 (1H, d), 8.36 (1H, d), 9.35 (1H, brs)

(56) 53 mg (0.33 mmol) of 2-chloro-5-chloromethyl pyridine dissolved in 6 ml of anhydrous acetonitrile was added to 68 mg (0.33 mmol) of the 2-chloro-2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide synthesized by the aforementioned method, and subsequently, 50 mg (0.36 mmol) of potassium carbonate was added thereto and the resulting mixture was heated and refluxed for 1 hours. After the reaction was completed, the reaction solution was returned to room temperature and then concentrated under reduced pressure. Diethyl ether was added thereto to precipitate a solid, and thus the solid was collected and dried to obtain the subject material. Amount obtained 49 mg (yield 45%).

(57) 1H-NMR (CDCl3, , ppm): 5.56 (2H, s), 6.92 (1H, t), 7.33 (1H, d), 7.82 (1H, m), 7.91 (1H, dd), 8.02 (1H, d), 8.45 (1H, d), 8.48 (1H, d)

(58) 13C-NMR (CDCl3, , ppm): 53.8, 115.2, 120.1 (t), 122.1, 124.8, 139.0, 140.0, 142.3, 150.0, 151.9, 159.1, 159.1, 165.8 (t)

(59) MS: m/z=332 (M+H)

Synthetic Example P9

2,2,2-trichloro-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-acetamide (Compound P235)

(60) 70 mg (0.27 mmol) of the 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride obtained by the method described in another method of Synthetic Example P1 was dissolved in 4 ml of anhydrous dichloromethane, 94 l (0.68 mmol, 68 mg) of triethylamine and 33 g (0.27 mmol, 49 mg) of trichloroacetyl chloride were added thereto in sequence, and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was completed, water was added thereto to stop the reaction and liquid separation was performed with dichloromethane and water. The organic layer was washed once with water and twice with 1% hydrochloric acid, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Diethyl ether was added thereto to precipitate a solid, and thus the solid was collected and dried to obtain the subject material. Amount obtained 61 mg (yield 62%).

(61) 1H-NMR (CDCl3, , ppm): 5.59 (2H, s), 6.86 (1H, t), 7.32 (1H, d), 7.78 (1H, td), 7.91 (2H, m), 8.43 (1H, d), 8.50 (1H, d)

(62) MS: m/z=364 (M+H)

Synthetic Example P10

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,3,3,3-pentafluoropropanamide (Compound P242)

(63) 300 mg (3.19 mmol) of 2-aminopyridine was dissolved in 15 ml of anhydrous dichloromethane, 919 mg (4.78 mmol) of EDC-HCl, 583 mg (4.78 mmol) of DMAP and 397 l (628 mg, 3.83 mmol) of pentafluoropropionic acid were added thereto in sequence, and the resulting mixture was stirred at room temperature overnight. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed once with water and twice with 1% hydrochloric acid, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 85 mg (yield 11%) of 2,2,3,3,3-pentafluoro-N-(pyridin-2(1H)-ylidene)propanamide.

(64) 52 mg (0.32 mmol) of 2-chloro-5-chloromethyl pyridine dissolved in 8 ml of anhydrous acetonitrile and 49 mg (0.35 mmol) of potassium carbonate were added to 77 mg (0.32 mmol) of the 2,2,3,3,3-pentafluoro-N-(pyridin-2(1H)-ylidene)propanamide obtained by the aforementioned method, and the resulting mixture was heated and refluxed for 11 hours. After the reaction was completed, the reaction solution was returned to room temperature to filter insoluble materials, and the filtrate was concentrated under reduced pressure. The filtrate was purified by silica gel column chromatography (hexane:ethyl acetate=1:3) to obtain the subject material. Amount obtained 12 mg (yield 10%).

(65) 1H-NMR (CDCl3, , ppm): 5.56 (2H, s), 6.90 (1H, td), 7.32 (1H, d), 7.79 (2H, m), 7.84 (1H, d), 8.43 (1H, d), 8.56 (1H, d)

(66) MS: m/z=366 (M+H)

Synthetic Example P11

N-[1-((2-chloropyrimidin-5-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (Compound P243)

(67) 1.04 g (8.13 mmol) of 2-chloro-5-methyl pyrimidine was dissolved in 30 ml of carbon tetrachloride, 1.73 g (9.75 mmol) of N-bromosuccinimide and 20 mg of benzoyl peroxide were added thereto, and the resulting mixture was heated and refluxed for 6 hours. After the reaction was completed, the reaction solution was returned to room temperature, concentrated under reduced pressure and purified by silica gel column chromatography (hexane:ethyl acetate=3:1) to obtain 641 mg (yield 38%) of 5-bromomethyl-2-chloropyridine.

(68) 1H-NMR (CDCl3, , ppm): 4.42 (2H, s), 8.66 (2H, s)

(69) 104 mg (0.50 mmol) of the 5-bromomethyl-2-chloropyridine obtained by the aforementioned method was dissolved in 6 ml of anhydrous acetonitrile, 96 mg (0.50 mmol) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetoamide obtained by the method described in (1) of Synthetic Example P1 and 76 mg (0.55 mmol) of potassium carbonate were added thereto, and the resulting mixture was heated and refluxed for 1 hour. After the reaction was completed, the reaction solution was returned to room temperature to filter off insoluble materials, and the filtrate was concentrated under reduced pressure. Diethyl ether was added thereto to precipitate a solid, and thus the solid was collected, washed with diethyl ether, and then dried under reduced pressure in a desiccator to obtain the subject material. Amount obtained 92 mg (yield 58%).

(70) 1H-NMR (CDCl3, , ppm): 5.54 (2H, s), 6.98 (1H, m), 7.87 (1H, m), 8.18 (1H, m), 8.48 (1H, m), 8.83 (2H, m)

(71) 13C-NMR (CDCl3, , ppm): 60.0, 115.6, 117.1 (q), 122.1, 127.5, 139.2, 142.9, 158.8, 160.3 (2C), 161.4, 163.8 (q)

(72) MS: m/z=317 (M+H)

(73) The compounds of P213 to P226, P228, P230, P232 to P234, P240 and P244 shown in the following Table were synthesized by the methods in accordance with Synthetic Examples P1 to P11.

(74) TABLE-US-00040 Com- IR (KBr, pound .sup.1H-NMR v, cm.sup.1) No. Ar R1a Y (CDCl3, , ppm) or MS Table 40-1 P212 6-chloro- CF3 H 5.57 (2H, s), 6.92 m/z = 3-pyridyl (1H, td), 7.31 (1H, 316 d), 7.80 (1H, td), (M + H) 7.87 (1H, dd), 7.99 (1H, dd), 8.48 (2H, m) P213 2-chloro- CF3 H 5.61 (2H, s), 6.93 m/z = 5- (1H, dd), 7.68 (1H, s), 322 thiazolyl 7.83 (1H, td), 7.97 (M + H) (1H, d), 8.53 (1H, d) P214 6-chloro- OCH3 H 3.74 (3H, s), 5.40 m/z = 3-pyridyl (2H, s), 6.45 (1H, 278 td), 7.29 (1H, d), (M + H) 7.46 (2H, m), 7.73 (1H, dd), 8.12 (1H, dd), 8.40 (1H, d) P215 6-chloro- CF3 5-Cl 5.53 (2H, s), 7.34 m/z = 3-pyridyl (1H, d), 7.71 (1H, 350 dd), 7.87 (1H, dd), (M + H) 7.94 (1H, s), 8.49 (1H, d) 8.55 (1H, s) P216 6-chloro- CF3 5-F 5.54 (2H, s), 7.34 m/z = 3-pyridyl (1H, d), 7.70 (1H, m), 334 7.80 (1H, m), 7.88 (M + H) (1H, dd), 8.48 (1H, d), 8.64 (1H, m) P217 6-chloro- CF3 4-Cl 5.49 (2H, s), 6.85 m/z = 3-pyridyl (1H, dd), 7.35 (1H, 350 d), 7.76 (1H, dd), (M + H) 7.85 (1H, dd), 8.44 (1H, d), 8.62 (1H, s) P218 2-chloro- CF3 5-Cl 5.56 (2H, s), 7.68 m/z = 5- (1H, s), 7.74 (1H, 356 thiazolyl dd), 7.84 (1H, d), (M + H) 8.58 (1H, d) Table 40-2 P219 2-chloro- CF3 5-F 5.60 (2H, s), 7.69 m/z = 5- (1H, s), 7.72 (1H, 340 thiazolyl td), 7.86 (M + H) 8.67, (1H, m) P220 2-chloro- CF3 4-Cl 5.58 (2H, s), 6.90 m/z = 5- (1H, d), 7.67 (1H, s), 356 thiazolyl 7.90 (1H, d), 8.61 (M + H) (1H, s) P221 6-chloro- CF3 3-Me 2.31 (3H, s), 5.50 m/z = 3-pyridyl (2H, s), 6.98 (1H, m), 330 7.34 (1H, d), 7.73 (M + H) (1H, dd), 7.77 (2H, m), 8.42 (1H, d) P222 6-chloro- CF3 4-Me 2.40 (3H, S), 5.49 m/z = 3-pyridyl (2H, s), 6.70 (1H, 330 dd), 7.32 (1H, d), (M + H) 7.70 (1H, d), 7.86 (1H, dd), 8.37 (1H, s), 8.43 (1H, d) P223 6-chloro- CF3 5-Me 2.29 (3H, s), 5.52 m/z = 3-pyridyl (2H, s), 7.32 (1H, d), 330 7.62 (1H, s), 7.65 (M + H) (1H, dd), 7.88 (1H, dd), 8.46 (1H, d), 8.50 (1H, d) P224 phenyl CF3 H 5.58 (2H, s), 6.81 m/z = (1H, m), 7.37 (4H, m), 281 7.77 (2H, m), 8.50 (M + H) (1H, d) P225 4- CF3 H 5.52 (2H, s), 6.85 m/z = chlorophenyl (1H, m), 7.30 (2H, d), 315 7.36 (2H, d), 7.75 (M + H) (1H, td), 7.84 (1H, d), 8.47 (1H, d) P226 3-pyridyl CF3 H 5.57 (2H, s), 6.86 m/z = (1H, m), 7.26-7.35 282 (2H, m), 7.78 (1H, (M + H) td), 7.86 (1H, m), 8.63 (2H, m), 8.67 (1H, d) P227 6-chloro- CF3 H 5.54 (2H, s), 6.89 m/z = 5-fluoro- (1H, td), 7.76 (1H, 334 3-pyridyl dd), 7.80 (1H, td), (M + H) 7.85 (1H, d), 8.29 (1H, d), 8.57 (1H, d) Table 40-3 P228 6- CF3 H 5.62 (2H, s), 6.90 m/z = trifluoromethyl- (1H, t), 7.69 (1H, 350 3-pyridyl d), 7.81 (1H, t), (M + H) 7.88 (1H, d), 8.06 (1H, d), 8.56 (1H, d), 8.78 (1H, s) P229 6-chloro- CF3 H 5.56 (2H, s), 6.89 m/z = 3-pyridyl (1H, td), 6.94 (1H, 300 d), 7.79 (1H, td), (M + H) 7.87 (1H, d), 8.03 (1H, m), 8.31 (1H, s), 8.54 (1H, d) P230 5,6- CF3 H 5.49 (2H, s), 6.89 m/z = dichloro- (1H, t), 7.79-7.90 350 3-pyridyl (2H, m), 8.04 (1H, (M + H) d), 8.37 (1H, d), 8.56 (1H, m)

(75) TABLE-US-00041 Com- IR (KBr, pound .sup.1H-NMR v, cm.sup.1) No. Ar R1a Y (CDCl3, , ppm) or MS Table 41-1 P231 6-bromo- CF3 H 5.52 (2H, s), 6.88 m/z = 3-pyridyl (1H, t), 7.48 (1H, d), 360 7.78 (2H, m), 7.84 (M + H) (1H, d), 8.44 (1H, d), 8.53 (1H, d) P232 6-chloro- CF3 4-F 5.52 (2H, s), 6.71 m/z = 3-pyridyl (1H, m), 7.35 (1H, d), 334 7.86 (1H, dd), 7.94 (M + H) (1H, m), 8.33 (1H, dd), 8.44 (1H, d) P233 6-chloro- CF3 3-F 5.53 (2H, s), 6.74 m/z = 3-pyridyl (1H, m), 7.33 (1H, d), 334 7.87 (1H, dd), 8.07 (M + H) (1H, m), 8.29 (1H, dd), 8.45 (1H, d) P234 6-chloro- CHCl2 H 5.54 (2H, s), 6.02 m/z = 3-pyridyl (1H, s), 6.77 (1H, t), 330 7.32 (1H, m), 7.69 (M + H) (1H, m), 7.77 (1H, d), 7.89 (1H, m), 8.42 (1H, m), 8.49 (1H, s) P235 6-chloro- CCl3 H 5.59 (2H, s), 6.86 m/z = 3-pyridyl (1H, t), 7.32 (1H, d), 364 7.78 (1H, td), 7.91 (M + H) (2H, m), 8.43 (1H, d), 8.50 (1H, d) P236 6-chloro- CHCl2 H 4.17 (2H, s), 5.46 m/z = 3-pyridyl (2H, s), 6.64 (1H, 296 td), 7.31 (1H, d), (M + H) 7.60 (1H, td), 7.64 (1H, dd), 7.80 (1H, dd), 8.32 (1H, d), 8.45 (1H, d) Table 41-2 P238 6-chloro- CHF3 H 5.52 (2H, s), 5.90 m/z = 3-pyridyl (1H, t), 6.79 (1H, 298 td), 7.33 (1H, d), (M + H) 7.71 (1H, m), 7.77 (1H, dd), 7.85 (1H, dd), 8.45 (1H, d), 8.50 (1H, d) P239 6-chloro- CF2Cl H 5.56 (2H, s), 6.92 m/z = 3-pyridyl (1H, t), 7.33 (1H, d), 332 7.82 (1H, m), 7.91 (M + H) (1H, dd), 8.02 (1H, d), 8.45 (1H, d), 8.48 (1H, d) P240 6-chloro- CHClBr H 5.53 (1H, d), 5.58 m/z = 3-pyridyl (1H, d), 6.06 (1H, s), 374 6.76 (1H, td), 7.32 (M + H) (1H, d), 7.69 (1H, m), 7.70 (1H, m), 7.90 (1H, dd), 8.40 (1H, d), 8.50 (1H, d) P241 6-chloro- CHBr2 H 5.56 (2H, s), 5.99 m/z = 3-pyridyl (1H, s), 6.78 (1H, 418 td), 7.33 (1H, d), (M + H) 7.69 (1H, td), 7.76 (1H, dd), 7.93 (1H, dd), 8.39 (1H, d), 8.50 (1H, d) P242 6-chloro- CF2CF3 H 5.56 (2H, s), 6.90 m/z = 3-pyridyl (1H, td), 7.32 (1H, 366 d), 7.79 (2H, m), 7.84 (M + H) (1H, d), 8.43 (1H, d), 8.56 (1H, d) P243 2-chloro-5- CF3 H 5.54 (2H, s), 6.98 m/z = pyrimidinyl (1H, m), 7.87 (1H, m), 317 8.18 (1H, m), 8.48 (M + H) (1H, m), 8.83 (2H, m) P244 6-chloro- CH2Br H 4.17 (2H, s), 5.46 3-pyridyl (2H, s), 6.63 (1H, td), 7.31 (1H, d), 7.60 (1H, td), 7.65 (1H, dd), 7.80 (1H, dd), 8.32 (1H, d), 8.47 (1H, d)

Synthetic Example 1

2,2-difluoro-N-[1-((6-fluoropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]acetamide (Compound 3-3)

(76) ##STR00074##

(77) (1) 400 mg (4.26 mmol) of 2-aminopyridine was dissolved in 10 ml of anhydrous dichloromethane, 322 l (490 mg, 5.11 mmol) of difluoroacetic acid, 982 mg (5.10 mmol) of EDC-HCl and 622 mg (5.11 mmol) of DMAP were added thereto, and the resulting mixture was stirred at room temperature for 61 hours. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed once with water and twice with a 1% HCl aqueous solution, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 102 mg (yield 14%) of 2,2-difluoro-N-(pyridin-2(1H)-ylidene)acetamide.

(78) 1H-NMR (CDCl3, , ppm): 6.03 (1H, t), 7.15 (1H, m), 7.73 (1H, td), 8.20 (1H, d), 8.34 (1H, dd), 8.72 (1H, brs)

(79) (2) 128 mg (0.75 mmol) of 5-bromomethyl-2-fluoropyridine was dissolved in 3 ml of anhydrous DMF, 116 mg (0.68 mmol) of 2,2-difluoro-N-[pyridin-2(1H)-ylidene]acetamide was dissolved in 3 ml of anhydrous DMF and added thereto, and subsequently, 103 mg (0.75 mmol) of potassium carbonate was added thereto and the resulting mixture was stirred at 65 C. for 2 hours. After the reaction was completed, the reaction solution was returned to room temperature, and ethyl acetate and water were added thereto to perform liquid separation. The organic layer was washed with 1% hydrochloric acid, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. A small amount of hexane and diethyl ether were added thereto to precipitate crystals, and thus the crystals were collected and dried to obtain the subject material. Amount obtained 50 mg (yield 26%).

Synthetic Example 2

N-[1-((6-chloropyridin-3-yl)methyl)pyrimidin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (Compound 190-2)

(80) ##STR00075##

(81) (1) 300 mg (1.86 mmol) of 2-chloro-5-chloromethyl pyridine was dissolved in 6 ml of anhydrous DMF, 118 mg (1.24 mmol) of 2-aminopyrimidine was added thereto, and the resulting mixture was stirred at 80 C. for 8 hours. After the reaction was completed, the reaction solution was returned to room temperature to distill off DMF under reduced pressure. Diethyl ether was added thereto, and thus crystallization was occurred on the wall surface of an eggplant flask. Diethyl ether was removed by decantation and dried well to obtain 1-((6-chloropyridin-3-yl)methyl)pyrimidin-2(1H)-imine hydrochloride. Amount obtained 107 mg (yield 34%)

(82) (2) 71 mg (0.27 mmol) of the 1-((6-chloropyridin-3-yl)methyl)pyrimidin-2(1H)-imine hydrochloride obtained by the aforementioned method was suspended in 5 ml of anhydrous dichloromethane, 114 l (0.83 mmol, 83 mg) of triethylamine and 53 l (0.38 mmol) of trifluoroacetic anhydride were added thereto in sequence, and the resulting mixture was stirred at room temperature for 2 hours. After the reaction was completed, dichloromethane and water were added to the reaction solution to perform liquid separation, and the organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. A small amount of diethyl ether was added thereto to precipitate crystals, and thus the crystals were collected, washed with a small amount of diethyl ether, and then dried to obtain the subject material. Amount obtained 24 mg (yield 28%).

Synthetic Example 3

2,2,2-trifluoroethyl-[1-((6-chloropyridin-3-yl)methyl)pyridin-(2H)-ylidene]carbamate (Compound 1-17)

(83) ##STR00076##

(84) (1) 3.00 g (18.6 mmol) of 2-chloro-5-chloromethyl pyridine was dissolved in 20 ml of anhydrous DMF, 1.75 g (18.6 mmol) of 2-aminopyridine was added thereto, and the resulting mixture was stirred at 80 C. for 8 hours and at room temperature for 5 hours. After the reaction was completed, DMF was distilled off under reduced pressure, acetonitrile was added thereto to precipitate a solid, and the solid was collected, washed well with acetonitrile and then dried to obtain 2.07 g (yield 44%) of 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride.

(85) 1H-NMR (DMSO-d6, , ppm): 5.65 (2H, s), 6.96 (1H, t), 7.23 (1H, m), 7.57 (1H, d), 7.80 (1H, m), 7.91 (1H, m), 8.28 (1H, m), 8.49 (1H, d)

(86) (2) 10 ml of anhydrous acetonitrile was added to 150 mg (0.66 mmol) of the 1-[(6-chloropyridin-3-yl)methyl]pyridin-2(1H)-imine hydrochloride obtained by the aforementioned method, 177 mg (0.66 mmol) of 4-nitrophenyl (2,2,2-trifluoroethyl)carbamate and 200 mg (1.46 mmol) of potassium carbonate were added, and the resulting mixture was stirred at 50 C. for 2 hours. After the reaction was completed, the reaction solution was returned to room temperature to filter off insoluble materials, and the filtrate was concentrated under reduced pressure. Dichloromethane and water were added thereto to perform liquid separation, and the organic layer was washed with 1% hydrochloric acid, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. A small amount of diethyl ether was added thereto to precipitate crystals, and thus the crystals were collected and dried well to obtain the subject material. Amount obtained 48 mg (yield 21%).

Synthetic Example 4

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroethanethioamide (Compound 1-20)

(87) ##STR00077##

(88) (1) 25 g (270 mmol) of 2-aminopyridine was dissolved in 200 ml of anhydrous dichloromethane, 41 ml (30 g, 300 mmol) of triethylamine was added thereto, and the mixture was cooled to 0 C. 38 ml (57 q, 270 mmol) of anhydrous trifluoroacetic acid was added dropwise thereto over 15 minutes, and the resulting mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was injected into about 100 ml of iced water, and the mixture was stirred for 10 minutes. The mixture was transferred to a separatory funnel to perform liquid separation, and the organic layer was washed twice with 150 ml of water and twice with 150 ml of a 1% HCl aqueous solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain 36 g (yield 71%) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide.

(89) 1H-NMR (CDCl3, , ppm): 7.20 (1H, m), 7.83 (1H, m), 8.20 (1H, d), 8.35 (1H, d), 10.07 (1H, brs)

(90) 13C-NMR (CDCl3, , ppm): 115.3, 115.5 (q), 121.6, 139.1, 147.9, 149.5, 155.3 (q)

(91) (2) 20 g (126 mmol) of 2-chloro-5-chloromethyl pyridine was dissolved in 200 ml of anhydrous acetonitrile, 24 g (126 mmol) of 2,2,2-trifluoro-N-(pyridin-2(1H)-ylidene)acetamide obtained by the above-described method and 21 g (151 mmol) of potassium carbonate were added thereto, and the resulting mixture was heated and refluxed for 6 hours, and then stirred at room temperature for 10 hours. After the reaction was completed, the reaction solution was filtered and the filtrate was concentrated under reduced pressure. Diethyl ether was added thereto for crystallization, and the crystals thus obtained were collected and washed well with diethyl ether and water. The crystals thus obtained were dried under reduced pressure at 60 C. for 1 hour to obtain N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (P212). Amount obtained 26 g (yield 66%).

(92) 1H-NMR (CDCl3, , ppm): 5.57 (2H, s), 6.92 (1H, td), 7.31 (1H, d), 7.80 (1H, td), 7.87 (1H, dd), 7.99 (1H, dd), 8.48 (2H, m)

(93) 13C-NMR (CDCl3, , ppm): 53.8, 115.5, 117.2 (q), 122.1, 124.7, 130.0, 139.2, 140.0, 142.5, 149.7, 151.8, 158.9, 163.5 (q)

(94) MS: m/z=316 (M+H)

(95) (3) 180 ml of toluene was added to 16.3 g (36.7 mmol) of phosphorus pentasulfide, 6.72 g (63.4 mmol) of sodium carbonate was added thereto and the resulting mixture was stirred at room temperature for 5 minutes. 20.0 q (63.4 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide obtained by the above-described method was added thereto, and the resulting mixture was stirred at 50 C. for 19 hours. 150 ml of ethyl acetate was added to the reaction solution, the resulting mixture was stirred at 50 C. for 10 minutes, then insoluble materials were filtered off, and 250 ml of ethyl acetate was used to wash the mixture. The mixture was transferred to a separatory funnel, washed therein with 300 ml of a saturated sodium bicarbonate water and 200 ml of a saturated saline solution, and then concentrated under reduced pressure. 200 ml of water was added thereto to precipitate crystals. The mixture was stirred at room temperature for 1 hour, and then the crystals were collected, subjected to slurry washing twice with 150 ml of water and twice with 150 ml of hexane, and dried at 60 C. under reduced pressure for 2 hours to obtain the subject material. Amount obtained 19.5 g (yield 94%).

(96) 1H-NMR (CDCl3, , ppm): 5.48 (2H, s), 7.12 (1H, td), 7.34 (1H, d), 7.77 (1H, dd), 7.96 (1H, m), 8.05 (1H, dd), 8.45 (1H, d), 8.56 (1H, d)

(97) MS: m/z=332 (M+H)

Synthetic Example 5

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoro-N-methylacetimidamide (Compound 1-42)

(98) ##STR00078##

(99) 150 mg (0.45 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroethanethioamide (1-20) synthesized by the method in Synthetic Example 4 was dissolved in 5 ml of methanol, 105 l (42 mg, 1.36 mmol) of methylamine (40% methanol solution) and 124 mg (0.45 mmol) of silver carbonate were added thereto, and the resulting mixture was stirred at 50 C. for 1 hour. After the reaction was completed, the reaction solution was returned to room temperature and subjected to suction filtration by using celite to remove insoluble materials. Ethyl acetate and water were added thereto to perform liquid separation, and the organic layer was dried over anhydrous magnesium sulfate, then concentrated under reduced pressure and purified with silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain the subject material. Amount obtained 81 mg (yield 56%).

Synthetic Example 6

N-(aryloxy)-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetimidamide (Compound 1-507)

(100) ##STR00079##

(101) 30 mg (0.09 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroethanethioamide (1-20) synthesized by the method in Synthetic Example 4 was dissolved in 5 ml of ethanol, 50 mg (0.45 mmol) of O-ally hydroxylamine hydrochloride, 62 l (0.45 mmol, 45 mg) of triethylamine and 25 mg (0.09 mmol) of silver carbonate were added thereto, and the resulting mixture was stirred at 50 C. for 5 hours and 20 minutes. After the reaction was completed, the reaction solution was returned to room temperature to filter off insoluble materials. The filtrate was concentrated under reduced pressure to perform liquid separation with ethyl acetate and 1% hydrochloric acid, then the ethyl acetate layer was washed with a saturated saline solution, and dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The ethyl acetate layer was purified by a TLC plate (one sheet of 0.5 mm plate, evolved with hexane:ethyl acetate=1:1) to obtain the subject material. Amount obtained 15 mg (yield 45%).

Synthetic Example 7

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoro-N-hydroxyacetimidamide (Compound 1-499)

(102) ##STR00080##

(103) 25 ml of ethanol was added to 1.00 g (3.00 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroethanethioamide (1-20) 1 synthesized by the method in Synthetic Example 4, 1.04 g (15.0 mmol) of hydroxylamine hydrochloride and 2.00 ml (1.50 g, 15.0 mmol) of triethylamine were added thereto in sequence, and the resulting mixture was stirred at 50 C. for 21.5 hours. After the reaction was completed, ethyl acetate and 1% hydrochloric acid were added to the reaction solution to perform liquid separation, and the organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The organic layer was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain the subject material. Amount obtained 625 mg (yield 63%).

Synthetic Example 8

N-(benzoyloxy)-N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetimidamide (Compound 1-519)

(104) ##STR00081##

(105) 30 mg (0.09 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoro-N-hydroxyacetimidamide (1-499) synthesized by the method in Synthetic Example 7 was dissolved in 3 ml of anhydrous acetonitrile, 24 l (17 mg, 0.17 mmol) of triethylamine and 20 g (22 mg, 0.17 mmol) of benzoyl chloride were added thereto in sequence, and the resulting mixture was stirred at room temperature for 10 minutes. After the reaction was completed, ethyl acetate and 1% hydrochloric acid were added to the reaction solution to perform liquid separation, and the organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The organic layer was purified by a TLC plate (one sheet of 0.5 mm plate, evolved with hexane:ethyl acetate=1:1) to obtain the subject material. Amount obtained 26 mg (yield 67%).

Synthetic Example 9

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoro-N-((propylcarbamoyl)oxy)acetimidamide (Compound 1-534)

(106) ##STR00082##

(107) 5 ml of anhydrous acetonitrile was added to 11 mg (0.13 mmol) of normal propyl isocyanate, 40 mg (0.12 mmol) of the N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoro-N-hydroxyacetimidamide (1-499) synthesized by the method in Synthetic Example 7 and 4 mg (0.04 mmol) of potassium-t-butoxide were added thereto, and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and ethyl acetate and a saturated saline solution were added thereto to perform liquid separation. The ethyl acetate layer was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and purified by a TLC plate (one sheet of 0.5 mm plate, evolved with hexane:ethyl acetate=1:3) to obtain the subject material. Amount obtained 16 mg (yield 32%).

Synthetic Example 10

Diisopropyl 1-((6-chloropyridin-3-yl)methyl)pyridyn-2(1H)-ylidenphospholamide trithioate (Compound 1-702)

(108) ##STR00083##

(109) 4.0 g (15.7 mmol) of 1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-imine hydrochloride obtained by the above-described method was suspended in 24.6 ml of dichloromethane, and under ice-cooling 1.35 ml of phosphorous trichloride over 10 mins, following 3.16 g (31.2 mmol) of triethylamine dissolved in 37 ml of dichloromethane was added thereto. After the mixture was stirred for 2 hours at room temperature, 499 mg (15.6 mmol) of sulfur was added to the mixture, and the mixture was stirred over night at room temperature. Under ice-cooling 3.16 g (31.2 mmol) of triethylamine, following 2.38 g (31.2 mmol) of 2-propanethiol dissolved in 10 ml of dichloromethane were added to the mixture, additionary the mixture was stirred for a day. After the reaction was completed, the reaction solution was concentrated under reduced pressure, and was extracted by 100 ml of diethylether twice. The ether solution was concentrated under reduced pressure, and 2.49 g of cruede compounds was obtained. 186 mg of crude compound was purified by a TLC plate (5 sheets of 0.5 mm plate, evolved with ethyl acetate) to obtain the subject material (47 mg. yield 9%) and (1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene)phosphoramidothioic dichloride (19 mg. yield 5%).

(110) ##STR00084##

(1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene)phosphoramidothioic dichloride

Synthetic Example 11

N-[1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-ylidene]-1,1,1-trifluoromethanesulfinamide (Compound 1-703)

(111) ##STR00085##

(112) 330 mg (2 mmol) of sodium trifluoromethanesulfonate was added by 2 ml of ethylacetate and 154 mg (1 mmol) of phosphorus oxychloride and stirred for 5 min at room temperature. And 220 mg (0.86 mmol) of 1-((6-chloropyridin-3-yl)methyl)pyridin-2(1H)-imine hydrochloride obtained by the above-described method was added to the mixture, and stirred for 2 hours. After the reaction was completed, the reaction mixture was purified by silica-gel column chromatography (eluent ethylacetate:hexane=1:0) to obtain the subject material (115 mg. yield 39%)

(113) The compounds shown in the following Table were prepared by the method in accordance with Synthetic Examples 1 to 11.

(114) TABLE-US-00042 TABLE 42 Reaction Compound Base and temperature, Method Yield No. Raw material 1 Raw material 2 the like Solvent Time (Table) (%) 266-2 69 mg (0.43 mmol) of 84 mg (0.43 mmol) 71 mg (0.52 Acetonitrile reflux, A 32 2-chloro-5- of 2,2,2-trifluoro- mmol) of 20 h (chloromethyl)pyridine N-(1,3,4-thiadiazol- potassium 2(3H)- carbonate ylidene))acetamide 444-2 56 mg (0.41 mmol) of 66 mg (0.34 mmol) 56 mg (0.41 Acetonitrile reflux, A 21 2-chloro-5- of 2,2,2-trifluoro- mmol) of 20 h (chloromethyl)thiazole N-(1,3,4-thiadiazol- potassium 2(3H)- carbonate ylidene))acetamide 190-2 71 mg (0.27 mmol) of 53 l (0.38 mmol) 53 l (0.38 Dichloromethane Room B 28 1-((6-chloropyridin-3- of anhydrous mmol) of temperature, yl)methyl)pyrimidin- trifluoroacetic triethylamine 1 h 2(1H)-imine acid hydrochloride 201-2 120 mg (0.47 mmol) of 99 l (0.71 mmol) 160 l (1.17 Dichloromethane Room B 11 1-((6-chloropyridin- of anhydrous mmol) of temperature, 3-yl)methyl)pyrazin- trifluoroacetic triethylamine 30 min 2(1H)-imine acid hydrochloride 223-2 530 mg (2.07 mmol) of 390 l (2.79 mmol) 537 l (2.79 Dichloromethane Room B 14 2-chloro-2-((6- of anhydrous mmol) of temperature, chloropyridin-3- trifluoroacetic triethylamine 2 h yl)methyl)pyridazin- acid 3(2H)-imine hydrochloride 146-2 113 mg (0.70 mmol) of 145 mg (0.70 mmol) 116 mg (0.84 Acetonitrile reflux, A 15 2-chloro-5- of 2,2,2-trifluoro- mmol) of 13 h (chloromethyl)pyridine N-(3-hydroxypyridin- potassium 2(1H)- carbonate ylidene))acetamide 224-2 190 mg (0.73 mmol) of 168 l (1.20 mmol) 220 l (1.60 Dichloromethane Room B 16 2-((2-chlorothiazol-5- of anhydrous mmol) of temperature, yl)methyl)pyridazin- trifluoroacetic acid triethylamine 5 min 3(2H)-imine hydrochloride 102-2 116 mg (0.72 mmol) of 155 mg (0.72 mmol) 109 mg (0.79 Acetonitrile reflux, A 22 2-chloro-5- of N-(3-cyanopyridin- mmol) of 8 h (chloromethyl)pyridine 2(1H)-ylidene))2,2,2- potassium trifluoroacetamide carbonate 212-2 59 mg (0.37 mmol) of 70 mg (0.37 mmol) 55 mg (0.40 Acetonitrile reflux, A 32 2-chloro-5- of 2,2,2-trifluoro- mmol) of 7 h (chloromethyl)pyridine N-(pyrimidin-4(3H)- potassium ylidene))acetamide carbonate 1-20 20.0 g (63.4 mmol) of 16.3 g (36.7 mmol) 6.72 mg (63.4 Toluene 50 C., D 94 N-[1-((6-chloropyridin-3- of phosphorus mmol) of 19 h yl)methyl)pyridin-2(1H)- pentasulfide sodium ylidene]-2,2,2- carbonate trifluoroacetamide 12-2 78 mg (0.38 mmol) of 73 mg (0.38 mmol) 58 mg (0.42 Acetonitrile reflux, A 44 2-chloro-4- of 2,2,2-trifluoro- mmol) of 3.5 h (bromomethyl)pyridine N-(pyridin-2(1H)- potassium ylidene))acetamide carbonate 213-2 79 mg (0.47 mmol) of 90 mg (0.47 mmol) 72 mg (0.52 Acetonitrile reflux, A 42 2-chloro-5- of 2,2,2-trifluoro- mmol) of 12 h (chloromethyl)thiazole N-(pyrimidin-4(3H)- potassium ylidene))acetamide carbonate 1-17 150 mg (0.66 mmol) of 177 mg (0.66 mmol) 200 mg (1.46 Acetonitrile 50 C., C 21 1-[(6-chloropyridin-3- of 4-nitrophenyl(2,2,2- mmol) of 2 h yl)methyl]pyridin-2(1H)- trifluoroethyl)carbamate potassium imine hydrochloride carbonate 1-18 150 mg (0.66 mmol) of 184 mg (0.66 mmol) 200 mg (1.46 Acetonitrile 50 C., C 30 1-[(6-chloropyridin-3- of 4-nitrophenyl(1,1,1- mmol) of 2 h yl)methyl]pyridin-2(1H)- trifluoropropan-2- potassium imine hydrochloride yl)carbamate carbonate 1-19 150 mg (0.66 mmol) of 220 mg (0.66 mmol) 200 mg (1.46 Acetonitrile 50 C., C 27 1-[(6-chloropyridin-3- of 1,1,1,3,3,3- mmol) of 3 h yl)methyl]pyridin- hexafluoropropan- potassium 2(1H)-imine 2-yl(4- carbonate hydrochloride nitrophenyl)carbamate 7-2 116 mg (0.72 mmol) of 137 mg (0.72 mmol) 110 mg (0.80 Acetonitrile reflux, A 49 2-chloro-5- of 2,2,2-trifluoro- mmol) of 5 h (chloromethyl)pyrazine N-(pyridin-2(1H)- potassium ylidene))acetamide carbonate 1-13 200 mg (0.78 mmol) of 103 l (1.17 mmol) EDC- Dichloromethane Room B 21 1-[(6-chloropyridin-3- of 2,2,2- HCl225 mg(1.17 mmol), temperature, yl)methyl]pyridin- trifluoropropionic DMAP238 mg(1.95 12 h 2(1H)-imine acid mmol) hydrochloride

(115) TABLE-US-00043 TABLE 43 Reaction Compound Base and temperature, Method Yield No. Raw material 1 Raw material 2 the like Solvent Time (Table) (%) 168-2 273 mg (1.70 mmol) of 350 mg (1.70 mmol) 248 mg (1.80 DMF 65 C., A 15 2-chloro-5- of 2,2,2-trifluoro- mmol) of 2 h (chloromethyl)pyridine N-(5-hydroxypyridin- potassium 2(1H)- carbonate ylidene))acetamide 1-21 23 mg (0.077 mmol) of 41 mg (0.092 mmol) 10 mg (0.092 THF Room D 49 N-[1-((6-chloropyridin-3- of phosphorus mmol) of temperature, yl)methyl)pyridin-2(1H)- pentasulfide sodium 2 h ylidene]-2,2- carbonate difluoroacetamide 3-20 30 mg (0.10 mmol) of 49 mg (0.11 mmol) 12 mg (0.11 THF Room D 49 N-[1-((6-fluoropyridin-3- of phosphorus mmol) of temperature, yl)methyl)pyridin-2(1H)- pentasulfide sodium 3 h ylidene]-2,2,2- carbonate trifluoroacetamide 4-20 30 mg (0.083 mmol) of 41 mg (0.09 mmol) 10 mg (0.09 THF Room D 61 N-[1-((6-bromopyridin-3- of phosphorus mmol) of temperature, yl)methyl)pyridin-2(1H)- pentasulfide sodium 3 h ylidene]-2,2,2- carbonate trifluoroacetamide 3-3 116 mg (0.72 mmol) of 116 mg (0.68 mmol) 110 mg (0.80 Acetonitrile reflux, A 27 2-fluoro-5- of 2,2-difluoro-N- mmol) of 6 h (bromomethyl)pyridine (pyridin-2(1H)- potassium ylidene))acetamide carbonate 4-3 50 mg (0.20 mmol) of 35 mg (0.20 mmol) 33 mg (0.24 Acetonitrile reflux, A 53 2-bromo-5- of 2,2-difluoro-N- mmol) of 6 h (bromomethyl)pyridine (pyridin-2(1H)- potassium ylidene))acetamide carbonate 5-5 46 mg (0.21 mmol) of 50 mg (0.21 mmol) 35 mg (0.25 Acetonitrile reflux, A 26 5-(bromomethyl)-2-chloro- of 2,2,3,3,3- mmol) of 2 h 3-fluoropyridine pentafluoro-N- potassium (pyridin-2(1H)- carbonate ylidene))propanamide 6-5 43 mg (0.21 mmol) of 50 mg (0.21 mmol) 35 mg (0.25 Acetonitrile reflux, A 21 5-(bromomethyl)-2- of 2,2,3,3,3- mmol) of 2 h chloropyrimidine pentafluoro-N- potassium (pyridin-2(1H)- carbonate ylidene))propanamide 1-22 37 mg (0.11 mmol) of 49 mg (0.11 mmol) 12 mg (0.11 THF Room D 31 2-chloro-N-[1-((6- of phosphorus mmol) of temperature, chloropyridin-3- pentasulfide sodium 4 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2- difluoroacetamide 1-23 31 mg (0.085 mmol) of 38 mg (0.085 mmol) 9 mg (0.0854 THF Room D 59 N-[1-((6-chloropyridin-3- of phosphorus mmol) of temperature, yl)methyl)pyridin-2(1H)- pentasulfide sodium 4 h ylidene]-2,2,3,3,3- carbonate pentafluoropropanamide 5-20 36 mg (0.11 mmol) of 49 mg (0.11 mmol) 12 mg (0.11 THF Room D 100 N-[1-((6-chloro-5- of phosphorus mmol) of temperature, fluoropyridin-3- pentasulfide sodium 4 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroacetamide 5-3 65 mg (0.29 mmol) of 50 mg (0.29 mmol) 48 mg (0.35 Acetonitrile reflux, A 38 5-(bromomethyl)-2-chloro- of 2,2-difluoro-N- mmol) of 3 h 3-fluoropyridine (pyridin-2(1H)- potassium ylidene))acetamide carbonate 6-3 60 mg (0.29 mmol) of 5- 50 mg (0.29 mmol) 48 mg (0.35 Acetonitrile reflux, A 37 (bromomethyl)-2- of 2,2-difluoro-N- mmol) of 3 h chloropyrimidine (pyridin-2(1H)- potassium ylidene))acetamide carbonate 8-2 73 mg (0.45 mmol) of 97 mg (0.51 mmol) 83 mg (0.60 DMF 65 C., A 32 3-chloro-6- of 2,2,2-trifluoro- mmol) of 3 h (chloromethyl)pyridazine N-(pyridin-2(1H)- potassium ylidene))acetamide carbonate 5-4 54 mg (0.24 mmol) of 50 mg (0.24 mmol) 41 mg (0.30 Acetonitrile reflux, A 51 5-(bromomethyl)-2-chloro- of 2-chloro-2,2- mmol) of 6 h 3-fluoropyridine difluoro-N-(pyridin- potassium 2(1H)- carbonate ylidene))acetamide 4-4 60 mg (0.24 mmol) of 50 mg (0.24 mmol) 41 mg (0.30 Acetonitrile reflux, A 48 2-bromo-5- of 2-chloro-2,2- mmol) of 6 h bromomethylpyridine difluoro-N-(pyridin- potassium 2(1H)- carbonate ylidene))acetamide 6-4 49 mg (0.24 mmol) of 50 mg (0.24 mmol) 41 mg (0.30 Acetonitrile reflux, A 55 5-(bromomethyl)-2- of 2-chloro-2,2- mmol) of 6 h chloropyrimidine difluoro-N-(pyridin- potassium 2(1H)- carbonate ylidene))acetamide 4-5 65 mg (0.26 mmol) of 50 mg (0.26 mmol) 41 mg (0.30 Acetonitrile reflux, A 8 2-bromo-5- of 2,2,3,3,3- mmol) of 2 h bromomethylpyridine pentafluoro-N- potassium (pyridin-2(1H)- carbonate ylidene))propanamide

(116) TABLE-US-00044 TABLE 44 Reaction Compound Base and temperature, Method Yield No. Raw material 1 Raw material 2 the like Solvent Time (Table) (%) 2-20 70 mg (0.22 mmol) of N- 107 mg (0.24 mmol) 25 mg (0.24 THF Room D 11 [1-((2-chlorothiazol-5- of phosphorus mmol) of temperature, yl)methyl)pyridin- pentasulfide sodium 4 h 2(1H)-ylidene]-2,2,2- carbonate trifluoroacetamide 10-20 130 mg (0.37 mmol) of 181 mg (0.41 mmol) 43 mg (0.41 THF Room D 93 2,2,2-trifluoro-N-[1- of phosphorus mmol) of temperature, ((6-trifluoromethyl)pyridin- pentasulfide sodium 4 h 3-yl)methyl)pyridin- carbonate 2(1H)-ylidene]- acetamide 3-4 110 mg (0.58 mmol) of 105 mg (0.51 mmol) 103 mg (0.75 DMF 65 C., A 63 2-fluoro-5- of 2-chloro-2,2- mmol) of 2 h (bromomethyl)pyridine difluoro-N- potassium (pyridin-2(1H)- carbonate ylidene))acetamide 3-5 110 mg (0.58 mmol) of 139 mg (0.58 mmol) 88 mg (0.63 DMF 65 C., A 22 2-fluoro-5- of 2,2,3,3,3- mmol) of 2 h (bromomethyl)pyridine pentafluoro-N- potassium (pyridin-2(1H)- carbonate ylidene)propanamide 11-20 40 mg (0.15 mmol) of 65 mg (0.11 mmol) 16 mg (0.15 THF Room D 53 2,2,2-trifluoro-N-[1- of phosphorus mmol) of temperature, ((tetrahydrofuran-3- pentasulfide sodium 4 h yl)methyl)pyridin- carbonate 2(1H)-ylidene]acetamide 1-14 200 mg (0.78 mmol) of 76 l (0. 94 mmol) 32 l (0.23 Acetonitrile reflux, B 28 1-[(6-chloropyridin-3- of acrylic acid mmol) of 1 h yl)methyl]pyridin- chloride triethylamine 2(1H)-imine hydrochloride 1-37 78 mg (0.28 mmol) of N- 125 mg (0.28 mmol) 30 mg (0.28 THF Room D 21 [l-((6-chloropyridin-3- of phosphorus mmol) of temperature, yl)methyl)pyridin- pentasulfide sodium 2 h 2(1H)-ylidene]- carbonate propionamide 1-39 180 mg (0.96 mmol) of N- 341 mg (0.75 mmol) 102 mg (0.96 THF Room D 29 [1-((6-chloropyridin- of phosphorus mmol) of temperature, 3-yl)methyl)pyridin- pentasulfide sodium 2 h 2(1H)-ylidene]- carbonate isobutyramide 1-40 54 mg (0.19 mmol) of N- 54 mg (0.19 mmol) 20 mg (0.19 THF Room D 12 [1-((6-chloropyridin-3- of phosphorus mmol) of temperature, yl)methyl)pyridin- pentasulfide sodium 2 h 2(1H)-ylidene]- carbonate cyclopropane carboxyamide 1-15 200 mg (0.78 mmol) of 83 mg (0.94 mmol) 320 l (2.34 Acetonitrile reflux, B 19 1-[(6-chloropyridin-3- of propyol mmol) of 5 h yl)methyl]pyridin-2(1H)- oxychloride triethylamine imine hydrochloride 1-35 26 mg (0.074 mmol) of N- 26 mg (0.06 mmol) 8 mg (0.074 THF Room D 23 [1-((6-chloropyridin-3- of phosphorus mmol) of temperature, yl)methyl)pyridin-2(1H)- pentasulfide sodium 1.5 h ylidene]-3- carbonate phyenylpropanamide 1-501 100 mg (0.30 mmol) of N- 145 mg (1.50 mmol) 205 l (1.50 Ethanol 50 C., F 14 [1-((6-chloropyridin-3- of O-ethyl mmol) of 19.5 h yl)methyl)pyridin-2(lH)- hydroxylamine triethylamine ylidene]-2,2,2- hydrochloride trifluoroethanethioamide 1-499 1.00 g (3.00 mmol) of N- 1.04 g (15.0 mmol) 2.00 ml (15.0 Ethanol 50 C., F 63 [1-((6-chloropyridin-3- of hydroxylamine mmol) of 21 h yl)methyl)pyridin-2(1H)- hydrochloride triethylamine ylidene]-2,2,2- trifluoroethanethioamide 1-510 1.00 g (3.00 mmol) of N- 239 mg (1.50 mmol) 205 l (1.50 Ethanol 50 C., F 20 [1-((6-chloropyridin-3- of O-benzyl mmol) of 19.5 h yl)methyl)pyridin-2(1H)- hydroxylamine triethylamine ylidene]-2,2,2- hydrochloride trifluoroethanethioamide 1-511 30 mg (0.09 mmol) of N- 20 l (0.28 mmol) 38 l (0.28 Acetonitrile Room G 72 [1-((6-chloropyridin-3- of acetyl chloride mmol) of temperature, yl)methyl)pyridin- triethylamine 15 min 2(1H)-ylidene]-2,2,2- trifluoro-N- hydroxyacetimidamide

(117) TABLE-US-00045 TABLE 45 Reaction Compound Base and temperature, Method Yield No. Raw material 1 Raw material 2 the like Solvent Time (Table) (%) 1-519 30 mg (0.09 mmol) of 20 l (0.17 mmol) 24 l (0.17 Acetonitrile Room G 67 N-[1-((6- of benzoyl mmol) of temperature, chloropyridin-3- chloride triethylamine 10 min yl)methyl)pyridin- 2(1H)-ylidene]-2,2,2- trifluoro-N- hydroxyacetimidamide 1-523 30 mg (0.09 mmol) of 20 l (0.26 mmol) 36 l (0.26 Acetonitrile Room G 49 N-[1-((6- of methyl mmol) of temperature, chloropyridin-3- chloroformate triethylamine 20 min yl)methyl)pyridin- 2(1H)-ylidene]-2,2,2- trifluoro-N- hydroxyacetimidamide 1-528 30 mg (0.09 mmol) of 20 l (0.18 mmol) 25 l (0.18 Acetonitrile Room G 100 N-[1-((6- of methanesulfonyl mmol) of temperature, chloropyridin-3- chloride triethylamine 20 min yl)methyl)pyridin- 2(1H)-ylidene]-2,2,2- trifluoro-N- hydroxyacetimidamide 1-531 30 mg (0.09 mmol) of 28 mg (0.15 mmol) 21 l (0.15 Acetonitrile Room G 100 N-[1-((6- of 4- mmol) of temperature, chloropyridin-3- methylbenzenesufonyl triethylamine 12 h yl)methyl)pyridin- chloride 2(1H)-ylidene]- 2,2,2-trifluoro-N- hydroxyacetimidamide 1-507 30 mg (0.09 mmol) of 50 mg (0.45 mmol) 62 l (0.45 Ethanol 50 C., F 45 N-[1-((6- of O-allyl mmol) of 5 h chloropyridin-3- hydroxylamine triethylamine, yl)methyl)pyridin- hydrochloride 25 mg (0.09 2(1H)-ylidene]- mmol) of silver 2,2,2- carbonate trifluoroethanethioamide 1-516 30 mg (0.09 mmol) of 20 l (0.25 mmol) 34 l (0.25 Acetonitrile Room G 64 N-[1-((6- of acryloyl mmol) of temperature, chloropyridin-3- chloride triethylamine 20 min yl)methyl)pyridin- 2(1H)-ylidene]- 2,2,2-trifluoro-N- hydroxyacetimidamide 1-518 30 mg (0.09 mmol) of 15 mg (0.18 mmol) EDC- Dichloromethane Room G 22 N-[1-((6- of 3-butynoate HCl135 mg(0.18 temperature, chloropyridin-3- mmol), 21 h yl)methyl)pyridin- DMAP22 mg(0.18 2(1H)-ylidene]- mmol) 2,2,2-trifluoro-N- hydroxyacetimidamide 1-527 30 mg (0.09 mmol) of 20 l (0.16 mmol) 22 l (0.16 Acetonitrile Room G 54 N-[1-((6- of phenyl mmol) of temperature, chloropyridin-3- chloroformate triethylamine 1.5 h yl)methyl)pyridin- 2(1H)-ylidene]- 2,2,2-trifluoro-N- hydroxyacetimidamide 1-521 30 mg (0.09 mmol) of 20 mg (0.14 mmol) 40 l (0.28 Acetonitrile Room G 46 N-[1-((6- of nicotinic acid mmol) of temperature, chloropyridin-3- chloride triethylamine 1.5 h yl)methyl)pyridin- hydrochloride 2(1H)-ylidene]- 2,2,2-trifluoro-N- hydroxyacetimidamide 1-43 100 mg (0.30 mmol) of Ethylamine (30% 90 l (0. 60 Ethanol 50 C., E 57 N-[1-((6- methanol mmol) of 1.5 h chloropyridin-3- solution, 0.60 triethylamine, yl)methyl)pyridin- mmol) 91 mg (0.33 2(1H)-ylidene]- mmol) of silver 2,2,2- carbonate trifluoroethanethioamide 1-536 50 mg (0.15 mmol) of 20 l (0.17 mmol) tBuOK Acetonitrile Room H 30 N-[1-((6- of benzyl 5 mg (0.04 mmol) temperature, chloropyridin-3- isocyanate 1 h yl)methyl)pyridin- 2(1H)-ylidene]- 2,2,2-trifluoro-N- hydroxyacetimidamide

(118) TABLE-US-00046 TABLE 46 Reaction Compound Base and temperature, Method Yield No. Raw material 1 Raw material 2 the like Solvent Time (Table) (%) 1-42 150 mg (0.45 mmol) of N- Methylamine 124 mg (0.45 Methanol 50 C., E 56 [1-((6-chloropyridin-3- (40% methanol mmol) of silver 1 h yl)methyl)pyridin-2(1H)- solution, carbonate ylidene]-2,2,2- 1.36 mmol) trifluoroethanethioamide 1-500 50 mg (0.15 mmol) of N- 63 mg (0.75 mmol) 103 l (0.75 Ethanol 50 C., F 50 [1-((6-chloropyridin-3- of O-methyl mmol) of 5 h yl)methyl)pyridin-2(1H)- hydroxylamine triethylamine, ylidene]-2,2,2- hydrochloride 41 mg (0.15 trifluoroethanethioamide mmol) of silver carbonate 1-504 50 mg (0.15 mmol) of N- 95 mg (0.75 mmol) 165 l (1.20 Ethanol 50 C., F 19 [1-((6-chloropyridin-3- of O-t-butyl mmol) of 5 h yl)methyl)pyridin-2(1H)- hydroxylamine triethylamine, ylidene]-2,2,2- hydrochloride 62 mg (0.23 trifluoroethanethioamide mmol) of silver carbonate 1-534 40 mg (0.12 mmol) of N- 11 mg (0.13 mmol) tBuOK4 mg (0.04 Acetonitrile Room H 32 [1-((6-chloropyridin-3- of n-propyl mmol) temperature, yl)methyl)pyridin-2(1H)- isocyanate 1 h ylidene]-2,2,2-trifluoro- N-hydroxyacetimidamide 1-535 40 mg (0.12 mmol) of N- 14 mg (0.13 mmol) tBuOK4 mg (0.04 Acetonitrile Room H 54 [1-((6-chloropyridin-3- of chloroethyl mmol) temperature, yl)methyl)pyridin-2(1H)- isocyanate 1 h ylidene]-2,2,2-trifluoro- N-hydroxyacetimidamide 1-72 150 mg (0.45 mmol) of N- 74 l (0.68 mmol) 137 mg (0.50 Ethanol 50 C., E 45 [1-((6-chloropyridin-3- of benzylamine mmol) of silver 3 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-150 100 mg (0.30 mmol) of N- 56 l (0.60 mmol) 91 mg (0.33 Ethanol 50 C., E 50 [1-((6-chloropyridin-3- of mmol) of silver 5 h yl)methyl)pyridin-2(1H)- methylthioethylamine carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-67 100 mg (0.30 mmol) of N- 74 l (1.20 mmol) 91 mg (0.33 Ethanol 50 C., E 49 [1-((6-chloropyridin-3- of 2- mmol) of silver 2 h yl)methyl)pyridin-2(1H)- aminoethanol carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-515 30 mg (0.09 mmol) of N- 40 l (0.44 mmol) 30 l (0.22 Acetonitrile 50 C., G 67 [1-((6-chloropyridin-3- of cyclopropane- mmol) of 2 h yl)methyl)pyridin-2(1H)- carboxylic triethylamine ylidene]-2,2,2-trifluoro- acid chloride N-hydroxyacetimidamide 1-56 100 mg (0.30 mmol) of N- 38 l (0.60 mmol) 91 mg (0.33 Ethanol 50 C., 2 h .fwdarw. E 57 [1-((6-chloropyridin-3- of propargylamine mmol) of silver reflux, 2 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-512 30 mg (0.09 mmol) of N- 20 l (0.23 mmol) 34 l (0.25 Acetonitrile Room G 32 [1-((6-chloropyridin-3- of propionyl mmol) of temperature, yl)methyl)pyridin-2(1H)- chloride triethylamine 30 min ylidene]-2,2,2-trifluoro- N-hydroxyacetimidamide 1-514 30 mg (0.09 mmol) of N- 20 l (0.19 mmol) 27 l (0.20 Acetonitrile Room G 61 [1-((6-chloropyridin-3- of isopropionyl mmol) of temperature, yl)methyl)pyridin-2(1H)- chloride triethylamine 2 h ylidene]-2,2,2-trifluoro- N-hydroxyacetimidamide 1-50 100 mg (0.30 mmol) of N- 48 l (1.20 mmol) 91 mg (0.33 Ethanol 50 C., 1.5 h .fwdarw. E 44 [1-((6-chloropyridin-3- of mmol) of silver reflux, 4.5 h yl)methyl)pyridin-2(1H)- cyclopropylamine carbonate ylidene]-2,2,2- trifluoroethanethioamide

(119) TABLE-US-00047 TABLE 47 Reaction Compound Base and temperature, Method Yield No. Raw material 1 Raw material 2 the like Solvent Time (Table) (%) 1-114 80 mg (0.30 mmol) of N- 48 l (0.36 mmol) 73 mg (0.33 Ethanol 50 C., E 52 [1-((6-chloropyridin-3- of 2- mmol) of silver 3.5 h yl)methyl)pyridin-2(1H)- phenyloxyethylamine carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-44 80 mg (0.30 mmol) of N- 60 l (0.72 mmol) 73 mg (0.33 Ethanol 50 C., E 55 [1-((6-chloropyridin-3- of n-propylamine mmol) of silver 2 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-118 100 mg (0.30 mmol) of N- 62 l (0.60 mmol) 91 mg (0.33 Ethanol 50 C., E 70 [1-((6-chloropyridin-3- of 2- mmol) of silver 5 h yl)methyl)pyridin-2(1H)- aminomethylpyridine carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-119 100 mg (0.30 mmol) of N- 62 l (0.60 mmol) 91 mg (0.33 Ethanol 50 C., E 58 [1-((6-chloropyridin-3- of 3- mmol) of silver 5 h yl)methyl)pyridin-2(1H)- aminomethylpyridine carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-47 100 mg (0.30 mmol) of N- 44 mg (0.60 mmol) 91 mg (0.33 Ethanol 50 C., E 49 [1-((6-chloropyridin-3- of n-butylamine mmol) of silver 5 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-55 100 mg (0.30 mmol) of N- CH2CHCH2NH2 91 mg (0.33 Ethanol 50 C., 2 h .fwdarw. E 53 [1-((6-chloropyridin-3- 34 mg (0.60 mmol) mmol) of silver reflux, 1 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-122 100 mg (0.30 mmol) of N- H2NCH2-(2-thienyl) 91 mg (0.33 Ethanol 50 C., 2 h .fwdarw. E 30 [1-((6-chloropyridin-3- 68 mg(0.60 mmol) mmol) of silver reflux, 1 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-45 100 mg (0.30 mmol) of N- 70 mg (1.20 mmol) 91 mg (0.33 Ethanol 50 C., 2 h .fwdarw. E 35 [1-((6-chloropyridin-3- of isopropylamine mmol) of silver reflux, 5 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-124 100 mg (0.30 mmol) of N- H2NCH2-(2-furanyl) 91 mg (0.33 Ethanol 50 C., E 56 [1-((6-chloropyridin-3- 58 mg(0.60 mmol) mmol) of silver 2.5 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-126 100 mg (0.30 mmol) of N- H2NCH2-(2- 91 mg (0.33 Ethanol 50 C., E 43 [1-((6-chloropyridin-3- thienyldrofuranyl) mmol) of silver 1 h yl)methyl)pyridin-2(1H)- 61 mg(0.60 mmol) carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-64 100 mg (0.30 mmol) of N- 110 mg (1.20 mmol) 91 mg (0.33 Ethanol 50 C., 1 h .fwdarw. E 22 [1-((6-chloropyridin-3- of aminoacetonitrile mmol) of silver reflux, 6 h yl)methyl)pyridin-2(1H)- hydrochloride carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-146 100 mg (0.30 mmol) of N- CH3OCH2CH2NH2 91 mg (0.33 Ethanol 50 C., E 30 [1-((6-chloropyridin-3- 45 mg(0.60 mmol) mmol) of silver 5 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-52 100 mg (0.30 mmol) of N- 51 mg (0.60 mmol) 91 mg (0.33 Ethanol 50 C., E 30 [1-((6-chloropyridin-3- of cyclopentylamine mmol) of silver 4 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-121 100 mg (0.30 mmol) of N- 65 mg (0.60 mmol) 91 mg (0.33 Ethanol 60 C., E 33 [1-((6-chloropyridin-3- of 4-aminomethyl mmol) of silver 4 h yl)methyl)pyridin-2(1H)- pyridine carbonate ylidene]-2,2,2- trifluoroethanethioamide

(120) TABLE-US-00048 TABLE 48 Reaction Compound Base and temperature, Method Yield No. Raw material 1 Raw material 2 the like Solvent Time (Table) (%) 1-53 100 mg (0.30 mmol) of N- 59 mg (0.60 mmol) 91 mg (0.33 Ethanol 60 C., E 28 [1-((6-chloropyridin-3- of cyclohexylamine mmol) of silver 2 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide 1-76 100 mg (0.30 mmol) of N- 73 mg (0.60 mmol) 91 mg (0.33 Ethanol 60 C., E 60 [1-((6-chloropyridin-3- of phenethylamine mmol) of silver 4 h yl)methyl)pyridin-2(1H)- carbonate ylidene]-2,2,2- trifluoroethanethioamide

(121) TABLE-US-00049 TABLE 49 MS or IR Compound (KBr, v, No. 1H-NMR (CDCl3, , ppm) cm.sup.1) 266-2 5.62 (2H, s), 7.33 (1H, d), 7.83 m/z = 323 (1H, d), 8.57 (2H, m) (M + H) 444-2 5.73 (2H, s), 7.69 (1H, s), 8.56 m/z = 329 (1H, s) (M + H) 190-2 5.39 (2H, s), 6.87 (1H, dd), m/z = 317 7.36 (1H, d), 7.91 (1H, dd), (M + H) 8.39 (1H, d), 8.49 (1H, s), 8.79 (1H, d) 201-2 5.45 (2H, s), 7.37 (1H, d), 7.65 m/z = 317 (1H, d), 7.87 (1H, dd), 7.99 (M + H) (1H, d), 8.49 (1H, 5), 9.80 (1H, d) 223-2 5.69 (2H, s), 7.31 (1H, d), 7.55 m/z = 317 (1H, dd), 7.92 (1H, dd), 8.28 (M + H) (1H, dd), 8.59 (1H, d), 8.78 (1H, dd) 146-2 5.64 (2H, s), 7.14 (1H, dd), m/z = 332 7.33 (1H, d), 7.47 (1H, dd), (M + H) 7.71 (1H, dd). 7.74 (1H, dd), 8.42 (1H, d), 11.64 (1H, br s) 224-2 5.78 (2H, s), 7.57, 7.63 (1H, m/z = 323 ddx2), 7.70 (1H, s), 8.26, 8.41 (M + H) (1H, dd x 2), 8.82, 9.04 (1H, ddx2) 102-2 5.56 (25, s), 7.15 (1H, m), 7.38 m/z = 341 (1H, d), 7.84 (1H, dd), 8.26 (M + H) (1H, dd), 8.48 (1H, d), 8.60 (1H, d) 212-2 5.43 (2H, s), 7.35 (1H, d), 7.87 m/z = 317 (1H, dd), 8.20 (1H, d), 8.29 (M + H) (1H, d), 8.51 (1H, d), 8.77 (1H, s) 1-20 5.48 (2H, s), 7.12 (1H, td), m/z = 332 7.34 (1H, d), 7.77 (1H, dd), (M + H) 7.96 (1H, m), 8.05 (1H, dd), 8.45 (1H, d), 8.56 (1H, d) 12-2 5.54 (2H, s), 6.96 (1H, m), 7.21 m/z = 316 (1H, d), 7.87 (1H, m), 7.97 (1H, (M + H) m), 8.34 (1H, d), 8.50 (1H, d) 213-2 5.51 (2H, s), 7.69 (1H, s), 8.25 m/z = 323 (1H, d), 8.30 (1H, d), 8.57 (1H, (M + H) s) 1-17 4.52 (2H, q), 5.44 (2H, s), 6.85 m/z = 346 (1H, td), 7.31 (1H, d), 7.57 (2H, (M + H) m), 7.79 (1H, dd), 8.14 (1H, d), 8.40 (1H, d) 1-18 1.44 (3H, d), 5.31 (1H, m), 5.42 m/z = 360 (2H, q), 6.54 (1H, td), 7.30 (1H, (M + H) d), 7.53 (2H, m). 7.79 (1H, dd), 8.10 (1H, d), 8.40 (1H, d) 1-19 5.47 (2H, s), 5.81 (1H, m), 6.69 m/z = 414 (1H, m), 7.31 (1H, d), 7.65 (1H, (M + H) m), 7.68 (1H, dd), 7.85 (1H, dd), 8.17 (1H, d), 8.40 (1H, d) 7-2 5.57 (2H, s), 6.91 (1H, m), 7.80 (1H, m), 8.10 (1H, m), 8.47 (1H, s), 8.49 (1H, d), 8.72 (1H, d) 1-13 3.22 (2H, q), 5.46 (2H, s), 6.65 m/z = 330 (1H, td), 7.31 (1H, d), 7.62 (1H, (M + H) m), 7.66 (1H, dd). 7.70 (1H, dd), 8.35 (1H, d), 8.41 (1H, d) 168-2 5.11 (2H, s), 7.40 (2H, m), 7.75 m/z = 332.0426 (1H, dd), 8.09 (1H, d), 8.15 (1H, (M + H) d), 8.46 (1H, d), 8.81 (1H, br s) 1-21 5.49 (2H, s), 6.21 (1H, t), 7.05 m/z m/z = 314.0346 (1H, td), 7.34 (1H, d), 7.82 (1H, (M + H) dd), 7.90 (1H, m), 7.94 (1H, dd), 8.45 (1H, d), 8.49 (1H, d) 3-20 5.51 (2H, s), 6.95 (1H, d), 7.15 m/z = 316.0559 (1H, td), 7.96 (2H, m), 8.09 (1H, (M + H) d), 8.29 (1H, d), 8.52 (1H, d) 4-20 5.47 (2H, s), 7.13 (1H, m), 7.50 m/z = 375.9 (1H, m), 7.66 (1H, m), 7.97 (1H, (M + H) m), 8.07 (1H, m), 8.43 (1H, s), 8.54 (1H, m) 3-3 5.54 (2H, s), 5.92 (1H, t), 6.79 (1H, td), 6.94 (1H, dd), 7.70 (1H, m), 7.78 (1H, dd), 8.03 (1H, td), 8.30 (1H, d), 8.50 (1H, d) 4-3 5.50 (2H, s), 5.90 (1H, t), 6.79 m/z = 342 (1H, m), 7.48 (1H, d), 7.74 (3H, (M + H) m), 8.43 (1H, d), 8.50 (1H, d) 5-5 5.56 (2H, s), 6.91 (1H, m), 7.69 m/z = 384.0372 (1H, dd), 7.82 (2H, m), 8.26 (1H, (M + H) d), 8.60 (1H, d) 6-5 5.52 (2H, s), 6.93 (1H, m), 7.86 m/z = 367.0687 (2H, m). 8.61 (1H, d), 8.75 (2H, (M + H) s) 1-22 5.49 (2H, s), 7.09 (1H, td), m/z = 347.9972 7.35 (1H, d), 7.78 (1H, dd), (M + H) 7.95 (2H, m), 8.46 (1H, d), 8.55 (1H, d) 1-23 5.47 (2H, s), 7.10 (1H, td) m/z = 382.0246 7.34 (1H, d), 7.68 (1H, dd), (M + H) 7.95 (2H, m), 8.41 (1H, d), 8.55 (1H, dd) 5-20 5.49 (2H, s), 7.10 (1H, m), 7.65 m/z = 350.0188 (1H, dd), 7.96 (1H, m), 8.00 (M + H) (1H, m), 8.27 (1H, d), 8.63 (1H, d) 5-3 5.53 (2H, s), 5.90 (1H, t), 6.80 m/z = 316.0507 (1H, td), 7.76 (2H, m), 8.29 (M + H) (1H, d), 8.52 (1H, d)

(122) TABLE-US-00050 TABLE 50 MS or IR Compound (KBr, v. No. 1H-NMR (CDCl3, , ppm) cm.sup.1) 6-3 5.45 (2H, s), 5.89 (1H, t), 6.83 m/z = 29.0532 (1H, td), 7.75 (1H, m), 7.82 (M + H) (1H, dd), 8.52 (1H, d), 8.81 (2H, s) 8-2 5.73 (2H, s), 6.90 (1H, td), 7.54 (1H, d), 7.81 (1H, td), 7.97 (1H, d), 8.22 (1H, d), 8.53 (1H, d) 5-4 5.54 (2H, s), 6.86 (1H, td), m/z = 350.0082 7.99 (3H, m). 8.30 (1H, d), 8.54 (M + H) (1H, d) 4-4 5.52 (2H, s), 6.86 (1H, td), m/z = 375.96 7.49 (1H, d), 7.77 (2H, m), 7.83 (M + H) (1H, dd), 8.45 (1H, d), 8.52 (1H, d) 6-4 5.49 (2H, s), 6.90 (1H, td), m/z = 333.0121 7.82 (1H, td), 7.87 (1H, dd), (M + H) 8.54 (1H, d), 8.81 (2H, s) 4-5 5.53 (2H, s), 6.89 (1H, td), m/z = 410 7.48 (1H, d), 7.70 (1H, dd), (M + H) 7.82 (2H, m), 8.41 (1H, d), 8.58 (1H, d) 2-20 5.57 (2H, s), 7.12 (1H, m), 7.68 m/z = 338 (1H, s), 7.97 (1H, m), 8.12 (1H, (M + H) d), 8.67 (1H, d) 10-20 5.58 (2H, s), 7.12 (1H, m), 7.70 m/z = 366 (1H, d), 7.97 (2H, m), 8.02 (1H, (M + H) d), 8.62 (1H, d), 8.77 (1H, s) 3-4 5.55 (2H, s), 6.86 (1H, td), m/z = 316 6.95 (1H, dd), 7.77 (1H, td), (M + H) 7.85 (1H, dd), 8.06 (1H, td), 8.31 (1H, d), 8.53 (1H, d) 3-5 5.56 (2H, s), 6.89 (1H, m), 6.94 m/z = 350 (1H, dd), 7.80 (2H, m), 7.97 (M + H) (1H, td), 8.27 (1H, d), 8.58 (1H. d) 11-20 1.69 (1H, m), 2.07 (1H, m), 2.84 m/z = 291 (1H, m), 3.59 (1H, dd), 3.71 (M + H) (1H, dd), 3.77 (1H, m), 3.96 (1H, m), 4.13 (1H, dd), 4.42 (1H, dd), 7.11 (1H, m), 7.92 (1H, dd), 7.98 (1H, m), 8.40 (1H, d) 1-14 5.44 (2H, s), 5.61 (1H, dd), m/z = 274 6.28 (1H, dd), 6.36 (1H, dd), (M + H) 6.52 (1H, m), 7.30 (1H, d), 7.52 (1H, m), 7.57 (1H, d), 7.73 (1H, dd), 8.28 (1H, d), 8.44 (1H, d) 1-37 1.28 (3H, t), 2.80 (2H, q), 5.41 m/z = 292 (2H, s), 6.86 (1H, t), 7.35 (1H, (M + H) d), 7.75 (3H, m), 8.10 (1H, d), 8.44 (1H, d) 1-39 1.26 (6H, d), 2.55 (1H, m), 5.51 m/z = 306 (2H, s), 6.98 (1H, m), 7.36 (1H, (M + H) d), 7.76 (1H, dd), 7.77 (2H, m), 8.08 (1H, d), 8.44 (1H, d) 1-40 0.92 (2H, m), 1.22 (2H, m), 2.40 m/z = 304 (1H, m), 5.36 (2H, s), 6.77 (1H, (M + H) td), 7.34 (1H, d), 7.66 (2H, m), 7.71 (1H, dd), 8.14 (1H, d), 8.41 (1H, d) 1-15 5.08 (2H, d), 5.40 (2H, s), 5.84 m/z = 286 (1H, t), 6.50 (1H, m), 7.30 (1H, (M + H) d), 7.50 (1H, m), 7.56 (1H, m), 7.80 (1H, dd), 8.25 (1H, d), 8.47 (1H, d) 1-35 3.18 (4H, m), 5.05 (2H, s), 6.83 m/z = 368 (1H, td), 7.05 (1H, t), 7.25 (M + H) (2H, m), 7.38 (3H, m), 7.59 (1H, dd), 7.67 (1H, d), 7.72 (1H, td), 7.99 (1H, d), 8.30 (1H, d) 1-501 1.20 (3H, t), 4.10 (2H, q), 5.22 m/z = 359 (2H, s), 6.15 (1H, td), 6.27 (M + H) (1H, d), 7.13 (1H, m), 7.27 (2H, m), 7.79 (1H, dd), 8.37 (1H, d) 1-499 5.26 (2H, s), 6.11 (1H, d), 6.31 m/z = 331 (1H, m), 7.31 (1H, m), 7.50 (1H, (M + H) d), 7.83 (1H, dd), 7.90 (1H, dd), 8.44 (1H, d), 11.0 (1H, s) 1-510 5.07 (2H, s), 5.19 (2H, s), 6.13 m/z = 421 (1H, td), 6.22 (1H, d), 7.07 (M + H) (1H, m), 7.18-7.40 (8H, m), 7.69 (1H, dd), 8.34 (1H, d) 1-511 1.99 (3H, s), 5.27 (2H, s), 6.37 m/z = 373 (2H, m), 7.31 (2H, m), 7.44 (1H, (M + H) dd), 7.76 (1H, dd), 8.37 (1H. d) 1-519 5.31 (2H, s), 6.36 (1H, t), 6.51 m/z = 435 (1H, d), 7.17 (1H, d), 7.25 (4H, (M + H) m), 7.50 (3H, m), 7.78 (1H, dd), 8.41 (1H, d) 1-523 3.84 (3H, s), 5.26 (2H, s), 6.35 m/z = 389 (1H, m), 6.40 (1H, d), 7.30 (2H, (M + H) m), 7.37 (1H, dd), 7.73 (1H, dd), 8.37 (1H, d) 1-528 3.14 (3H, s), 5.27 (2H, s), 6.44 m/z = 409 (1H, td), 6.54 (1H, dd), 7.32 m/z (M + H) (1H, d), 7.41 (2H, m), 7.68 (1H, dd), 8.39 (1H, d) 1-531 2.45 (3H, s), 5.23 (2H, s), 6.37 m/z = 485 (1H, d), 6.42 (1H, td), 7.29 (M + H) (4H, m), 7.45 (1H, d), 7.70 (1H, dd), 7.80 (2H, d), 8.35 (1H, d) 1-507 4.54 (2H, m), 5.16 (2H, m), 5.22 m/z = 371 (2H, s), 5.91 (1H, m), 6.17 (1H, (M + H) td), 6.29 (1H, d), 7.15 (1H, m), 7.27 (2H, m), 7.79 (1H, dd), 8.37 (1H, d)

(123) TABLE-US-00051 TABLE 51 MS or IR Compound (KBr, v, No. 1H-NMR (CDCl3, , ppm) cm.sup.1) 1-516 5.27 (2H, s), 5.76 (1H, dd), 5.91 m/z = 385 (1H, dd), 6.22 (1H, dd), 6.36 (1H, (M + H) m), 6.42 (1H, d), 7.29 (2H, m), 7.42 (1H, d), 7.76 (1H, dd), 8.37 (1H, d) 1-518 1.25 (1H, s), 1.98 (2H, s), 5.28 m/z = 397 (2H, s), 6.38 (2H, m), 7.30 (2H, m), (M + H) 7.41 (1H, d), 7.75 (1H, dd), 8.38 (1H, d) 1-527 5.28 (2H, s), 6.39 (1H, m), 6.50 m/z = 451 (1H, d), 7.13 (1H, d), 7.22-7.41 (M + H) (7H, m), 7.76 (1H, dd), 8.40 (1H, d) 1-521 5.30 (2H, s), 6.42 (1H, t), 6.52 m/z = 436 (1H, d), 7.20 (1H, d), 7.32 (2H, m), (M + H) 7.53 (1H, dd), 7.75 (1H, dd), 8.01 (1H, dd), 8.41 (1H, d), 8.54 (1H, d), 8.71 (1H, dd) 1-43 1.13(3H, t), 3.03 (2H, q), 5.15 (2H, m/z = 343 s), 6.12 (1H, m), 6.19 (1H, d), (M + H) 7.14(1H, m), 7.27 (1H, m), 7.33 (1H, d), 7.72 (1H, dd), 8.37 (1H, d) 1-536 4.48 (2H, d), 5.25 (2H, s), 6.36 m/z = 464 (1H, td), 6.41 (1H, d), 6.79 (1H, (M + H) m), 7.41 (7H, m), 7.73 (1H, dd), 8.40 (1H, d) 1-42 2.86 (3H, s), 5.16 (2H, s), 6.15 m/z = 329 (2H, m), 7.16 (1H, m), 7.26 (1H, (M + H) dd), 7.31 (1H, d), 7.73 (1H, dd), 8.38 (1H, d) 1-500 3.86 (3H, s), 5.22 (2H, s), 6.17 m/z = 345 (1H, m), 6.26 (1H, d), 7.14 (1H, m), (M + H) 7.20 (1H, dd), 7.30 (1H, d), 7.78 (1H, dd), 8.39 (1H, d) 1-504 1.23 (9H, s), 5.23 (25, s), 6.10 m/z = 387 (1H, m), 6.22 (1H, d), 7.09 (1H, m), (M + H) 1.20 (1H, dd), 7.26 (1H, m), 7.79 (1H, dd), 8.35 (1H, ) 1-534 0.95 (3H, t), 1.61 (2H, m), 3.23 m/z = 416 (2H, t) 5.24 (25, s), 6.32 (1H, t), (M + H) 6.39 (1H, d),6.48 (1H, m), 7.33 (3H, m), 7.74 (1H, dd), 8.40 (1H, d) 1-535 3.65 (4H, m), 5.25 (2H, s), 6.36 m/z = 436 (1H, t), 6.41 (1H, d), 6.82 (1H, (M + H) m), 7.36 (3H, m), 7.74 (1H, dd), 8.41 (1H, d) 1-72 4.22 (2H, s), 5.13 (2H, s), 6.14 m/z = 405 (1H, m), 6.21 (1H, d), 7.13 (1H, (M + H) m), 7.26 (7H, m), 7.68 (1H, dd), 8.36 (1H, d) 1-150 2.08 (3H, s), 2.70 (2H, t), 3.22 m/z = 389 (2H, t), 5.15 (2H, s), 6.16 (1H, (M + H) t), 6.22 (1H, d), 7.17 (1H, m), 7.29 (1H, d), 7.33 (1H, d), 7.70 (1H, dd), 8.38 (1H, d) 1-67 3.13 (2H, m), 3.73 (2H, t), 5.15 m/z = 359 (2H, s), 6.18 (2H, m), 7.17 (1H, (M + H) m), 7.33 (2H, m), 7.71 (1H, dd), 8.37 (1H, d) 1-515 0.82 (2H, m), 0.93 (2H, m), 1.40 m/z = 399 (1H, m), 5.27 (2H, s), 6.35 (1H, (M + H) m), 6.42 (1H, d), 7.31 (2H, m), 7.41 (1H, d), 7.77 (1H, dd), 8.38 (1H, d) 1-56 2.13 (1H, t), 3.85 (2H, d), 5.18 m/z = 353 (2H, s), 6.21 (1H, t), 6.25 (1H, (M + H) d), 7.18 (1H, m), 7.29 (1H, d), 7.33 (1H, d), 7.70 (1H, dd), 8.38 (1H, d) 1-512 1.02 (3H, t), 2.23 (2H, q), 5.26 m/z = 387 (2H, s), 6.34 (1H, m), 6.39 (1H, (M + H) m), 7.29 (2H, m), 7.40 (1H, d), 7.75 (1H, dd), 8.37 (1H, d) 1-514 0.97 (6H, s), 2.37 (1H, m), 5.26 m/z = 399 (2H, s), 6.35 (1H, m), 6.40 (1H, (M + H) d), 7.27 (2H, m), 7.42 (1H, dd), 7.77 (1H, dd), 8.38 (1H, d) 1-50 0.74 (2H, m), 0.85 (2H, m), 2.51 m/z = 355 (1H, m), 5.18 (2H, s), 6.12 (1H, (M + H) m), 6.30 (1H, d), 7.15 (1H, m), 7.27 (1H, m), 7.31 (1H, d), 7.79 (1H, dd), 8.39 (1H, d) 1-114 3.44 (2H, td), 4.18 (2H, t), m/z = 435 5.14 (2H, s), 6.15 (1H, td), (M + H) 6.26 (1H, d), 6.86 (2H, d), 6.92 (1H, m), 7.16 (1H, m), 7.28 (4H, m), 7.71 (1H, dd), 8.38 (1H, d) 1-44 0.83 (3H, t), 1.55 (2H, m), 2.91 m/z = 357 (2H, m), 5.14 (2H, s), 6.12 (1H, (M + H) td), 6.18 (1H, d), 7.13 (1H, m), 7.30 (2H, m), 7.71 (1H, dd), 8.36 (1H, d) 1-118 4.41 (2H, s), 5.15 (2H, s), 6.18 m/z = 406 (1H, t), 6.24 (1H, d), 7.14 (2H, (M + H) m), 7.26 (2H, m), 7.54 (1H, d), 7.68 (1H, dd), 7.71 (1H, dd), 8.38 (1H, d), 8.47 (1H, d) 1-119 4.22 (2H, s), 5.16 (2H, s), 6.20 m/z = 406 (2H, m), 7.15-7.30 (3H, m), 7.34 (M + H) (1H, dd), 7.61 (1H, d), 7.79 (1H, dd), 8.37 (1H, d), 8.42 (1H, d), 8.46 (1H, d)

(124) TABLE-US-00052 TABLE 52 MS or IR Compound (KBr, v, No. 1H-NMR (CDCl3, , ppm) cm.sup.1) 1-47 0.85 (3H, t), 1.25 (2H, m), 1.53 m/z = 371 (2H, m), 2.96 (2H, m), 5.14 (2H, (M + H) s), 6.10 (1H, m), 6.17 (1H, d), 6.99 (1H, m), 7.27 (2H, m), 7.70 (1H, dd), 8.36 (1H, d) 1-55 3.65 (2H, m), 5.04 (2H, m), 5.15 m/z = 355 (2H, s), 5.90 (1H, m), 6.13 (1H, (M + H) m), 6.20 (1H, d), 7.13 (1H, m), 7.28 (2H, m), 7.71 (1H, dd), 8.36 (1H, d) 1-122 4.41 (2H, s), 5.17 (2H, s), 6.17 m/z = 411 (2H, m), 6.82 (1H, m), 6.91 (1H, (M + H) m), 7.16 (2H, m), 7.30 (2H, m), 7.70 (1H, dd), 8.38 (1H, d) 1-45 1.02 (6H, , 3.34 (1H, m), 5.13 m/z = 357 (2H, s), 6.10 (1H, m), 6.24 (1H, (M + H) d), 7.11 (1H, m), 7.26 (1H, m), 7.31 (1H, d), 7.68 (1H, dd), 8.35 (1H, d) 1-124 4.20 (2H, s), 5.17 (2H, s), m/z = 395 6.13-6.29 (4H, m), 7.17 (1H, m), (M + H) 7.30 (3H, m), 7.71 (1H, dd), 8.38 (1H, d) 1-126 1.49 (1H, m), 1.84 (2H, m), 1.99 m/z = 399 (1H, m), 2.98 (1H, ddd), 3.14 (M + H) (1H, ddd), 3.73 (2H, m), 4.09 (1H, m), 5.13 (2H, m), 6.13 (1H, m), 6.20 (1H, d), 7.14 (1H, m), 7.30 (2H, m), 7.70 (1H, dd), 8.37 (1H, d) 1-64 4.01 (2H, s), 5.24 (2H, s), 6.34 m/z = 354 (2H, m), 7.34 (2H, m), 7.41 (1H, (M + H) dd), 7.66 (1H, dd), 8.36 (1H, d 1-146 3.21 (2H, m), 3.34 (2H, s), 3.57 m/z = 373 (2H, t), 5.14 (2H, s), 6.15 (1H, (M + H) m), 6.21 (1H, m), 7.15 (1H, m), 7.30 (2H, m), 7.72 (1H, dd), 8.37 (1H, d) 1-52 1.40-1.77 (8H, m), 3.48 (1H, m), m/z = 383 5.12 (2H, s), 6.09 (1H, m), 6.23 (M + H) (1H, d), 7.12 (1H, m), 7.24 (1H, m), 7.31 (1H, d), 7.69 (1H, dd), 8.35 (1H, d) 1-121 4.18 (2H, s), 5.14 (2H, s), 6.20 m/z = 406 (2H, m), 7.19 (3H, m), 7.26 (1H, (M + H) m), 7.35 (1H, dd), 7.75 (1H, dd), 8.36 (1H, d), 8.51 (2H, m) 1-53 0.98-1.72 (10H, m), 2.91 (1H, m/z = 397 m), 5.11 (2H, s), 6.11 (1H, td), (M + H) 6.24 (1H, d), 7.11 (1H, m), 7.29 (3H, m), 7.66 (1H, dd), 8.34 (1H, d) 1-76 2.90 (2H, t), 3.24 (2H, td), m/z = 419 5.07 (2H, s), 6.01 (1H, d), 6.09 (M + H) (1H, td), 7.02-7.30 (8H, m), 7.61 (1H, dd), 8.34 (1H, d) 267-2 4.34 (1H, d), 4.62 (1H, d), 6.40 1730, (1H, d), 7.20 (1H, d), 7.51 (2H, 1689, m), 7.59 (1H, dd), 7.63 (2H, m), 1556, 7.82 (1H, d), 8.23 (1H, d) 1467, 1440, 1418 253-2 5.31 (2H, s), 7.28 (2H, m), 7.50 1644, (1H, d), 7.72 (3H, m), 7.85 (1H, 1557, m), 8.25 (1H, d), 8.45 (1H, d) 1508, 1483 251-2 5.20 (2H, s), 7.26 (2H, m), 7.63 3065, (2H, m), 7.85 (2H, m), 8.02 (1H, 1696, d), 8.23 (2H, m) 1463, 1403 13-2 5.76 (2H, s), 6.91 (1H, m), 7.46 3060, (1H, m), 7.60 (1H, m), 7.70 (1H, 2226, d), 7.80 (2H, m), 6.12 (1H, d), 1641, 8.53 (1H, d) 1556, 1509 1-1 5.49 (2H, s), 6.67 (1H, m), 7.30 (1H, m), 7.60 (1H, m), 7.72 (2H, m), 7.81 (1H, dd), 8.42 (1H, d), 9.06 (1H, s) 1-41 5.64 (2H, s), 7.50 (2H, m), 7.70 m/z = 315.16 (1H, d), 7.78 (1H, dd), 8.27 (M + H) (1H, m), 8.37 (1H, d), 8.78 (1H, d) (methanol-d4)

(125) TABLE-US-00053 TABLE 53 MS or IR Compound (KBr, v, No. 1H-NMR (CDCl3, , ppm) cm.sup.1) 2-2 2.47 (2H, m), 4.17 (2H, t), 5.07 m/z = 322 (1H, d), 5.15 (1H, dd), 5.39 (2H, (M + H) s), 5.85 (1H, m), 6.43 (1H, td), 7.30 (1H, d), 7.44 (2H, m), 7.75 (1H, dd), 8.08 (1H, d), 8.40 (1H, d) 1-647 2.47 (2H, m), 4.17 (2H, t), 5.07 m/z = 318.1013 (1H, d), 5.15 (1H, dd), 5.39 (2H, (M + H) s), 5.85 (1H, m), 6.43 (1H, td), 7.30 (1H, d), 7.44 (2H, m), 7.75 (1H, dd), 8.08 (1H, d), 8.40 (1H, d) 1-670 3.35(2H, tdd), 5.17 (2H, s), 6.02 m/z = 379 (1H, tt), 6.23 (2H, m), 7.22 (1H, (M + H) m), 7.33 (2H, m), 7.69 (1H, dd), 8.37 (1H, d) 157-2 5.51 (2H, s), 6.63 (1H, dd), 7.42 m/z = 332 (1H, d), 7.77 (1H, d), 7.84 (1H, (M + H) dd), 8.26 (1H, d), 8.45 (1H, d) 1-10 1.61 (1H, m), 2.29 (2H, m), 4.73 m/z = 324 (2H, s), 7.26 (1H, m), 7.31 (1H, m), (M + H) 7.69 (1H, m), 7.79 (1H, m), 8.23 (1H, d), 8.40 (1H, d), 8.57 (1H, d) 580-2 5.47 (2H, s), 6.89 (1H, m), 7.47 m/z = 332 (2H, m), 7.82 (2H, m), 8.41 (1H, s), (M + H) 8.56 (1H, d) 1-671 0.87 (3H, t), 1.28 (10H, m), 1.55 m/z = 427 (2H, m), 2.96 (2H, t), 5.14 (2H, s), (M + H) 6.13 (1H, t), 6.18 (1H, d), 7.13 (1H, m), 7.30 (2H, m), 7.71 (1H, dd), 8.37 (1H, d) 1-658 0.87 (3H, t), 1.25 (26H, m), 1.55 m/z = 539 (2H, m), 2.96 (2H, t), 5.14 (2H, s), (M + H) 6.11 (1H, t), 6.17 (1H, d), 7.13 (1H, m), 7.30 (2H, m), 7.70 (1H, dd), 8.36 (1H, d) 1-659 0.87 (3H, t), 1.26 (18H, m), 1.53 m/z = 483 (2H, m), 2.95 (2H, t), 5.14 (2H, s), (M + H) 6.12 (1H, t), 6.18 (1H, d), 7.13 (1H, m), 7.31 (2H, m), 7.71 (1H, dd), 8.36 (1H, d) 1-660 0.74 (3H, t), 0.97 (3H, d), 1.42 m/z = 371 (2H, m), 3.08 (1H, m), 5.12 (2H, (M + H) dd), 6.09 (1H, t), 6.23 (1H, d), 7.11 (1H, m), 7.24 (1H, m), 7.30 (1H, d), 7.67 (1H, dd), 8.35 (1H, d) 1-681 0.77, 0.90 (6H, tx2), 1.40 (4H, m/z = 385 m), 2.97 (1H, m), 5.11 (2H, s), (M + H) 6.10 (1H, t), 6.25 (1H, d), 7.11 (1H, m), 7.24 (1H, d), 7.32 (1H, d), 7.66 (1H, dd), 8.34 (1H, d) 1-686 0.81, 0.91 (6H, tx2), 1.02-1.45 m/z = 413 (8H, m), 3.19 (1H, m), 5.12 (2H, (M + H) s), 6.10 (1H, t), 6.25 (1H, d), 7.11 (1H, m), 7.22 (1H, d), 7.30 (1H, d), 7.64 (1H, dd), 8.33 (1H, d) 1-661 0.81 (3H, t), 0.97 (38, d), m/z = 385 0.90-1.50 (4H, m), 3.19 (1H, m), (M + H) 5.07 (1H, d), 5.15 (1H, d), 6.09 (1H, t), 6.24 (1H, d), 7.11 (1H, m), 7.27 (2H, m), 7.66 (1H, dd), 8.34 (1H, d) 1-662 0.75 (3H, d), 0.80 (3H, d), 0.94 m/z = 385 (3H, d), 1.61 (1H, m), 2.86 (1H, (M + H) m), 5.11 (2H, s), 6.09 (1H, t), 6.23 (1H, d), 7.11 (1H, t), 7.25 (1H, d), 7.30 (1H, d), 7.66 (1H, dd), 8.34 (1H, d) 1-663 1.35 (3H, d), 4.33 (1H, q), 5.05 m/z = 419 (1H, d), 5.11 (1H, d), 6.00 (1H, (M + H) d), 6.08 (1H, t), 6.96 (1H, m), 7.15-7.26 (7H, m), 7.63 (1H, dd), 8.33 (1H, d) 1-664 1.55-1.75 (3H, m), 1.95 (1H, m), m/z = 445 2.70-2.88 (2H, m), 4.36 (1H, t), (M + H) 5.05 (1H, d), 5.20 (1H, d), 6.13 (1H, t), 6.38 (1H, d), 6.96 (1H, m), 7.02-7.20 (5H, m), 7.28 (1H, d), 7.62 (1H, dd), 8.3 (1H, d) 1-665 1.57 (3H, d), 4.78 (1H, d), 4.91 m/z = 469 (1H, d), 5.18 (1H, q), 5.80 (1H, (M + H) d), 5.93 (1H, t), 6.72 (1H, m), 7.05 (1H, d), 7.14 (1H, d), 7.38 (3H, m), 7.54 (1H, dd), 7.62 (1H, d), 7.66 (1H, d), 7.80 (1H, d), 7.84 (1H, d), 8.28 (1H, d) 1-666 0.74 (3H, t), 1.75 (2H, m), 4.03 m/z = 433 (1H, t), 5.06 (2H, dd), 5.85 (M + H) (1H, d), 6.05 (1H, m), 6.86 (1H, m), 7.10-7.28 (7H, m), 7.63 (1H, dd), 8.33 (1H, d) 1-667 1.34 (3H, d), 4.45 (1H, q), 5.11 m/z = 409 (1H, d), 5.16 (1H, d), 6.07 (1H, (M + H) m), 6.14 (1H, td), 6.26 (2H, m), 7.11 (1H, m), 7.28 (3H, m), 7.67 (1H, dd), 8.36 (1H, d) 1-676 5.06 (2H, s), 5.37 (1H, 5.38 m/z = 481 (1H, d), 6.07 (1H, t), 6.85 (1H, (M + H) t), 7.10-7.28 (12H, m), 7.61 (1H, d), 8.33 (1H, s) 1-668 0.79 (9H, s), 0.85 (3H, d), 2.89 m/z = 399 (1H, q), 5.11 (2H, s), 6.08 (1H, (M + H) t), 6.23 (1H, d), 7.10 (1H, t), 7.23 (1H, d), 7.30 (1H, d), 7.65 (1H, d), 8.34 (1H, s)

(126) TABLE-US-00054 TABLE 54 MS or IR Compound (KBr, v, No. 1H-NMR (CDCl3, , ppm) cm.sup.1) 47-2 5.68 (2H, d), 6.57 (1H, m), 7.34 m/z = 334 (1H, d), 7.80 (1H, m), 7.97 (1H, (M + H) dd), 8.39 (1H, d), 8.57 (1H, s) 91-2 5.92 (2H, s), 6.95 (1H, d), 7.30 m/z = 350 (1H, d), 7.69 (1H, m), 7.86 (1H, (M + H) dd), 8.49 (1H, dd), 8.53 (1H, d) 478-2 2.59 (3H, s), 5.77 (2H, s), 6.75 m/z = 330 (1H, d), 7.31 (1H, d), 7.63 (1H, (M + H) dd), 7.72 (1H, m), 8.33 (1H, d), 8.45 (1H, d) 479-2 2.73 (3H, s), 5.71 (2H, s), 6.73 m/z = 336 (1H, d), 7.63 (1H, s), 7.69 (1H, (M + H) t), 8.44 (1H, d) 1-51 1.60 (2H, m), 1.73 (1H, m), 2.03 m/z = 369 (4H, m), 3.75 (1H, m), 5.12 (2H, (M + H) s), 6.12 (1H, t), 6.16 (1H, d), 7.10 (1H, m), 7.25 (1H, d), 7.32 (1H, d), 7.71 (1H, dd), 8.37 (1H, d) 566-2 4.09 (3H, s), 5.71 (2H, s), 6.25 m/z = 346 (1H, d), 7.29 (1H, d), 7.74 (1H, (M + H) t), 7.97 (1H, dd), 8.17 (1H, d), 8.50 (1H, d) 488-2 1.77 (1H, m), 2.11 (1H, m), 2.62 m/z = 289 (3H, s), 2.98 (1H, m), 3.53 (1H, (M + H) dd), 3.67 (1H, dd), 3.78 (1H, m), 3.98 (1H, m), 4.22 (1H, m), 4.65 (1H, m), 6.73 (1H, d), 7.66 (1H, t), 8.32 (1H, d) 511-2 5.58 (2H, s), 7.38 (1H, d), 7.86 m/z = 361 (1H, dd), 8.40 (1H, dd), 8.47 (M + H) (1H, d), 8.55 (1H, d), 8.93 (1H, d) 1-669 1.42 (3H, d), 4.65 (1H, q), 5.12 m/z = 425 (2H, s), 6.13 (2H, m), 6.75 (1H, (M + H) d), 6.88 (1H, dd), 7.07 (1H, m), 7.11 (1H, d), 7.26 (2H, m), 7.65 (1H, dd), 8.35 (1H, d) 179-2 5.30 (2H, s), 6.43 (1H, dd), m/z = 332 6.66 (1H, dd), 7.40 (1H, d), (M + H) 7.60 (2H, m), 8.20 (1H, d) 555-2 3.87 (3H, s), 5.60 (2H, s), 7.51 m/z = 346 (1H, d), 7.88 (1H, dd), 7.93 (M + H) (1H, dd), 8.34 (1H, d), 8.49 (1H, d), 8.56 (1H, d) (DMSO-d6) 577-2 5.65 (2H, s), 6.87 (1H, td), m/z = 349 7.30 (1H, d), 7.81 (1H, m), 8.08 (M + H) (1H, dd), 8.13 (1H, d), 8.54 (1H, d) 544-2 3.93 (3H, s), 5.45 (2H, s), 6.49 m/z = 346 (1H, dd), 7.31 (1H, d), 7.66 (M + H) (1H, d), 7.83 (1H, dd), 8.13 (1H, d), 8.42 (1H, d) 168-2 5.62 (2H, s), 7.43 (1H, d), 7.64 m/z = 332 (1H, dd), 7.88 (1H, dd), 7.94 (M + H) (1H, d), 8.26 (1H, d), 8.49 (1H, d) 1-644 4.18 (2H, s), 4.68 (2H, s), m/z = 368 5.36 (2H, s), 6.55 (1H, m), (M + H) 7.16 (1H, d), 7.29 (1H, d), 7.35 (2H, m), 7.40 (2H, m), 7.52 (2H, m), 7.75 (1H, dd), 8.28 (1H, d), 8.40 (1H, d) 578-644 4.19 (2H, s), 4.69 (2H, s), m/z = 334 5.42 (2H, s), 6.52 (1H, m), (M + H) 7.20 (1H, m), 7.30 (1H, m), 7.32 (2H, m), 7.40 (2H, m), 7.55 (2H, m), 7.72 (1H, dd), 8.30 (1H, dd), 8.52 (1H, dd), 8.62 (1H, d) 1-703 5.20 (1H, d), 5.45 (1H,d), 1715, 1636, 6.55 (1H, m) 7.34 (1H, m), 1552, 1505, 7.50 (1H, m), 7.60 (1H, m), 1457, 1174, 7.79 (1H, dd), 8.39 (1H, d) 1144 1-707 5.43 (2H, s), 6.93 (1H, m), (EI-HRMS) 7.36 (1H , d), 7.77-7.85 (3H, m/z = m), 7.95 (1H, dd), 8.39 (1H, 351.0084 (M+) d) 1-706 1.20 (6H, m), 2.67 (4H, m), m/z = 298 5.22 (2H, s), 6.52 (1H, m),. (M + H) 7.31 (1H, m), 7.51 (1H, m), 7.60 (1H, dd), 7.73 (1H, m), 7.84 (1H, d), 8.41 (1H, d) 1-692 1.11(3H, t), 1.20 (3H, 3.76 m/z = 356 (2H, m), 3.92 (2H, m), 6.58 (1H, (M + H) m), 7.26 (1H, d)., 7.53 (2H, m), 7.74 (1H, dd), 8.12 (1H, d), 8.40 (1H, d) (DMSO-d6) 1-700 1.20 (6H, m), 2.67 (4H, m), 5.22 m/z = 404 (2H, s), 6.52 (1H, m),. 7.31 (1H, (M + H) m), 7.51 (1H, m), 7.60 (1H, dd), 7.73 (1H, m), 7.84 (1H, d), 8.41 (1H, d) 1-701 0.95 (6H, m), 1.56 (4H, m), 2.62 m/z = 432 (4H, m), 5.18 (2H, s), 6.52 (1H, (M + H) m), 7.34 (1H, m), 7.49 (1H, m), 7.59 (1H, m), 7.77 (1H, dd), 7.84 (1H, d), 8.42 (1H, d) 1-702 1.13-1.46 (m, 12H), 3.20 (m, 2H), m/z = 432 5.27 (s, 2H), 6.51 (m, 1H), 7.31 (M + H) (m, 1H), 7.52 (m, 1H), 7.63 (m, 1H), 7.78 (m, 2H), 8.43 (d, 1H) 1-646 1.31 (6H, d), 4.95 (1H, sep), 1646, 5.40 (2H, s), 6.40 (1H, m), 7.28 1620, (1H, d), 7.40 (2H, m), 7.73 (1H, 1548, dd) 8.05 (1H, m), 8.40 (1H, d) 1504, 1453, 1-645 5.18 (2H, s), 5.37 (2H, s), 6.43 1655, (1H, m), 7.25-7.36 (4H, m), 1518, 7.41-7.46 (4H, m), 7.72 (1H, 1455, dd), 8.12 (1H, m), 8.38 (1H, d) 1399, 1235 1-643 5.52 (2H, s), 6,78 (1H, m), 7.31 1633, (1H, d), 7.68-7.75 (3H, m), 8.39 1601, (1H, m), 8.56 (1H, s) 1541, 1502, 1482, 1453, 1384 2-643 5.51 (2H, s), 6.80 (1H, m), 7.60 1632, (1H, s), 7.75 (2H, m), 8.57 (1H, 1597, m) 1541, 1506, 1483, 1455, 1388

(127) Further, the synthetic methods in the Table are described as follows.

(128) A: the same method as in Synthetic Example 1

(129) B: the same method as in Synthetic Example 2

(130) C: the same method as in Synthetic Example 3

(131) D: the same method as in Synthetic Example 4

(132) E: the same method as in Synthetic Example 5

(133) F: the same method as in Synthetic Example 6

(134) G: the same method as in Synthetic Examples 7 and 8

(135) H: the same method as in Synthetic Example 9

PREPARATION EXAMPLE

Preparation Example

Preparation Example 1

Wettable Powder

(136) TABLE-US-00055 Compound P212 10% by weight Imidacloprid 20% by weight Clay 50% by weight White carbon 2% by weight Diatomaceous earth 13% by weight Calcium ligninsulfonate 4% by weight Sodium lauryl sulfate 1% by weight

(137) The ingredients were homogeneously mixed and ground to obtain wettable powder

Preparation Example 2

Water Dispersible Granule

(138) TABLE-US-00056 Compound P212 10% by weight Imidacloprid 20% by weight Clay 60% by weight Dextrin 5% by weight Alkyl maleate copolymer 4% by weight Sodium lauryl sulfate 1% by weight

(139) The ingredients were homogeneously ground and mixed, water was added thereto to knead the ingredients thoroughly and then the mixture was granulated and dried to obtain water dispersible granules.

Preparation Example 3

Flowables

(140) TABLE-US-00057 Compound 1-20 5% by weight Imidacloprid 20% by weight POE polystyrylphenyl ether sulfate 5% by weight Propylene glycol 6% by weight Bentonite 1% by weight 1% xanthan-gum aqueous solution 3% by weight PRONALEX-300 (TOHO Chemical 0.05% by weight Industry Co., Ltd.) ADDAC827 (KI Chemical Industry 0.02% by weight Co., Ltd.) Water added to 100% by weight

(141) All the ingredients except for the 1% xanthan-gum aqueous solution and a suitable amount of water were premixed together from the blending, and the mixture was then ground by a wet grinder. Thereafter, the 1% xanthan-gum aqueous solution and the remaining water were added thereto to obtain 100% by weight of flowables.

Preparation Example 4

Emulsifiable Concentrate

(142) TABLE-US-00058 Compound P212 2% by weight Imidacloprid 13% by weight N,N-dimethylformamide 20% by weight Solvesso 150 (Exxon Mobil Corporation) 55% by weight Polyoxyethylene alkyl aryl ether 10% by weight

(143) The ingredients were homogeneously mixed and dissolved to obtain an emulsifiable concentrate.

Preparation Example 5

Dust

(144) TABLE-US-00059 Compound P212 0.5% by weight Imidacloprid 1.5% by weight Clay 60% by weight Talc 37% by weight Calcium stearate 1% by weight

(145) The ingredients were homogeneously mixed to obtain dust.

Preparation Example 6

DL Dust

(146) TABLE-US-00060 Compound P212 1% by weight Tebufloquin 1% by weight Ethofenprox 1% by weight DL clay 94.5% by weight White carbon 2% by weight Light liquid paraffin 0.5% by weight

(147) The ingredients were homogeneously mixed to obtain dust.

Preparation Example 7

Microgranule Fine

(148) TABLE-US-00061 Compound P212 1% by weight Imidacloprid 1% by weight Carrier 94% by weight White carbon 2% by weight Hisol SAS-296 2% by weight

(149) The ingredients were homogeneously mixed to obtain dust.

Preparation Example 8

Granules

(150) TABLE-US-00062 Compound 1-20 2% by weight Chlorantraniliprole 1% by weight Bentonite 39% by weight Talc 10% by weight Clay 46% by weight Calcium ligninsulfonate 2% by weight

(151) The ingredients were homogeneously ground and mixed, water was added thereto to knead the ingredients thoroughly, and then the mixture was granulated and dried to obtain granules.

Preparation Example 9

Microcapsules

(152) TABLE-US-00063 Compound 1-20 2% by weight Imidacloprid 3% by weight Urethane resin 25% by weight Emulsifier/Dispersant 5% by weight Antiseptic 0.2% by weight Water 64.8% by weight

(153) Microcapsules were obtained by forming a urethane resin coating on the surface of particles of the compound represented by Formula (I) and imidacloprid particles using the ingredients by interfacial polymerization.

Preparation Example 10

Granules

(154) TABLE-US-00064 Compound P212 2% by weight Probenazole 24% by weight Sodium lauryl sulfate 1% by weight Bentonite 2% by weight Calcium stearate 1% by weight PVA 2% by weight Clay 68% by weight

(155) The ingredients were homogeneously ground and mixed, water was added thereto to knead the ingredients thoroughly, and then the mixture was granulated and dried to obtain granules.

Preparation Example 11

Granules

(156) TABLE-US-00065 Compound P212 2% by weight Chlorantraniliprole 1% by weight Probenazole 24% by weight Bentonite 40% by weight Talc 10% by weight Clay 21% by weight Calcium ligninsulfonate 2% by weight

(157) The ingredients were homogeneously ground and mixed, water was added thereto to knead the ingredients thoroughly, and then the mixture was granulated and dried to obtain granules.

Preparation Example 12

Liquid Drops

(158) TABLE-US-00066 Compound 1-20 10% by weight Fipronil 1% by weight Benzyl alcohol 73.9% by weight Propylene carbonate 15% by weight BHT 0.1% by weight

(159) The ingredients were homogeneously stirred and dissolved to obtain liquid drops.

Preparation Example 13

Liquid Drops

(160) TABLE-US-00067 Compound P212 48% by weight Fipronil 2% by weight Ethanol 50% by weight

(161) The ingredients were homogeneously mixed to obtain liquid drops.

Preparation Example 14

Emulsifiable Concentrate

(162) TABLE-US-00068 Compound 1-20 5% by weight Etoxazole 5% by weight Xylene 35% by weight Dimethyl sulfoxide 35% by weight

(163) The ingredients were dissolved, and 14% by weight of polyoxyethylene styryl phenyl ether and 6% calcium dodecylbenzenesulfonate were added thereto, and the mixture was thoroughly stirred and mixed to obtain a 10% emulsifiable concentrate.

Preparation Example 15

Liquid Drops

(164) TABLE-US-00069 Compound P212 10% by weight Etoxazole 5% by weight Glycol (glycol mono alkyl ether) 85% by weight BHT or BHA appropriate amount

(165) An appropriate amount of sorbitan monooleate or sorbitan monolaurate, caprylic acid monoglyceride or isostearic acid monoglyceride, or propylene glycol monocaprylate was added to the ingredients, and alcohol or propylene carbonate, N-methyl-2-pyrrolidone or water was added thereto to obtain liquid drops as 100% by weight.

REFERENCE TEST EXAMPLE

(166) <Foliar Treatment Test of Single Agent>

Reference Test Example 1

Pest Control Test of Plutella xylostella

(167) A leaf disk having a diameter of 5.0 cm was cut out from a cabbage in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed to the leaf disk. After an air drying process, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(168) As a result, compounds P212 and 1-20 exhibited insecticidal activity having a mortality of 80% or higher by a foliar treatment at 100 ppm.

Reference Test Example 2

Pest Control Test of Spodoptera litura

(169) A leaf disk having a diameter of 5.0 cm was cut out from a cabbage in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed to the leaf disk. After an air drying process, third instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(170) As a result, compounds P212 and 1-20 exhibited insecticidal activity having a mortality of 80% or higher by a foliar treatment at 500 ppm.

Reference Test Example 3

Pest Control Test of Aphis gossypii

(171) A leaf disk having a diameter of 2.0 cm was cut out from a cucumber in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed to the leaf disk. After an air drying process, first instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(172) As a result, compounds P212 and 1-20 exhibited insecticidal activity having a mortality of 80% or higher by a foliar treatment at 100 ppm.

Reference Test Example 4

Pest Control Test of Laodelphax striatella

(173) A drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was foliar sprayed to a rice seedling in pot culture. After an air drying process, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(174) As a result, compounds P212 and 1-20 exhibited insecticidal activity having a mortality of 80% or higher by a foliar treatment at 100 ppm.

Reference Test Example 5

Pest Control Test of Nilaparvata lugens

(175) A drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was foliar sprayed to a rice seedling in pot culture. After an air drying process, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Six days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(176) As a result, compounds P212 and 1-20 exhibited insecticidal activity having a mortality of 80% or higher by a foliar treatment at 100 ppm.

Reference Test Example 6

Pest Control Test of Sogatella furcifera

(177) A drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was foliar sprayed to a rice seedling in pot culture. After an air drying process, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Four days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(178) As a result, compounds P212 and 1-20 exhibited insecticidal activity having a mortality of 80% or higher by a foliar treatment at 100 ppm.

Reference Test Example 7

Pest Control Test of Nephotettix cincticeps

(179) A drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was foliar sprayed to a rice seedling in pot culture. After an air drying process, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Four days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(180) As a result, compound P212 exhibited insecticidal activity having a mortality of 80% or higher by a foliar treatment at 100 ppm.

Reference Test Example 8

Pest Control Test of trialeurodes vaporariorum

(181) Adult greenhouse whiteflies were released to a cucumber in pot culture and allowed to lay eggs overnight. One day after the onset of egg laying, the adults were removed and the eggs were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the completion of egg laying, a leaf disk having a diameter of 2.0 cm was cut out from the cucumber, it was confirmed that the eggs had been laid, and then a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed to the leaf disk. After the spraying, the leaf disk was left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Fourteen days after the spraying, larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality of larvae (%)={(number of eggs laidnumber of survived larvae)/number of eggs laid)}100

(182) As a result, compound P212 exhibited high insecticidal activity having a mortality of 80% or higher by a foliar treatment at 100 ppm.

Reference Test Example 9

Pest Control Test of Frankliniella occidentalis

(183) A leaf disk having a diameter of 2.8 cm was cut out from a kidney bean in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed to the leaf disk. After an air drying process, first instar larvae were released to the leaf disk. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(184) As a result, compounds P212 and 1-20 exhibited high insecticidal activity having a mortality of 80% or higher by a foliage treatment at 500 ppm.

Reference Test Example 10

Pest Control Test of Trigonotylus caelestialium

(185) Wheat seedling leaves and stems four days after the dissemination of seedlings were dipped for 30 seconds in a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available). After an air drying process, the wheat seedling leaves and stems were placed into a glass tube, and two second instar larvae of Trigonotylus coelestialium were released to the same glass tube. After the larvae were released, the tube was lidded to leave the larvae to stand in a thermostatic chamber at 25 C. In order to supply water to the wheat during the test, water was given to the wheat from the bottom of the glass tube. Three days after the treatment, the larvae were observed for survival or death, and the death rate of larvae was calculated by the following equation. Test in triplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(186) As a result, compounds P212 and 1-20 exhibited insecticidal activity having a mortality of 80% or higher by a dipping treatment of the drug solution at 50 ppm.

Reference Test Example 11

Pest Control Test of Plautia crossota stali

(187) A drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed to a young fruit of apple collected outdoors. After an air drying process, the young fruit was placed into a plastic cup, and two adults of Plautia crossota stali were released thereto. Six days after the release, the adults were observed for survival or death, the Mortality of adults was calculated by the following equation.
Mortality of adults (%)={number of dead adults/(number of survived adults+number of dead adults)}100

(188) As a result, compound P212 exhibited insecticidal activity having a mortality of 60% or higher by a foliar treatment at 50 ppm.

Reference Test Example 12

Pest Control Test of Oulema oryzae

(189) 1 L(/head) of a drug solution of the compound of Formula (I) prepared at a predetermined concentration with acetone was topically applied and treated to the back of adults collected outdoors by a micro syringe. After the drug treatment, the adults were transferred to rice seedlings and left to stand in a thermostatic chamber at 25 C. so as to obtain 5 heads per stem. Forty eight hours after the treatment, the adults were observed for survival or death, and the mortality of adults was calculated by the following equation. Test in duplicate.
Mortality of adults (%)={number of dead adults/(number of survived adults+number of dead adults)}100

(190) As a result, compound P212 exhibited high insecticidal activity having a mortality of 80% or higher in a throughput of 0.5 g/head.

Reference Test Example 13

Pest Control Test of Musca domestica

(191) The backs of female adults raised indoors were treated with 1 L(/head) of a drug solution of the compound of Formula (I) prepared at a predetermined concentration with acetone. After the drug treatment, the adults were transferred to a plastic cup and left to stand in a thermostatic chamber at 25 C. so as to obtain 5 heads per cup. Twenty four hours after the treatment, the agony situation of the adults was observed, and the rate of agonized adults was calculated by the following equation. Test in duplicate.
Mortality of adults (%)={number of dead adults/(number of survived adults+dead adults)}100

(192) As a result, compounds P212 and 1-20 exhibited high insecticidal activity having a mortality of 80% or higher in a throughput of 2 g/head.

(193) <Soil Drench Test of Single Agent>

Reference Test Example 14

Pest Control Test of Laodelphax striatella

(194) A rice seedling in pot culture was subjected to soil drench treatment with a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 10% acetone water. Three days after the treatment, ten second instar larvae of Laodelphax striatella were each released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(195) As a result, compounds P212 and 1-20 exhibited high insecticidal activity having a mortality of 80% or higher in a throughput of 0.05 mg/seedling.

Reference Test Example 15

Pest Control Test of Sogatella furcifera

(196) A rice seedling in pot culture was subjected to soil drench treatment with a drug solution of the compound of Formula (I) at a predetermined concentration, which had been prepared so as to be a 10% acetone water. Three days after the treatment, ten second instar larvae of Sogatella furcifera were each released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(197) As a result, compounds ?212 and 1-20 exhibited high insecticidal activity having a mortality of 80% or higher in a throughput of 0.05 mg/seedling.

Reference Test Example 16

Pest Control Test of Nilaparvata lugens

(198) A rice seedling in pot culture was subjected to soil drench treatment with a drug solution of the compound of Formula (I), which had been prepared so as to be a 10% acetone water. Three days after the treatment, ten second instar larvae of Nilaparvata lugens were each released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(199) As a result, compounds P212 and 1-20 exhibited high insecticidal activity having a death rate of 80% or higher in a throughput of 0.05 mg/seedling.

Reference Test Example 17

Pest Control Test of Lissorhoptrus oryzophilus

(200) A rice seedling in pot culture was subjected to soil drench treatment with a drug solution of the compound of Formula (I), which had been prepared so as to be a 10% acetone water. Two days after the treatment, five adults of Lissorhoptrus oryzophilus were each released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(201) As a result, compound P212 exhibited high insecticidal activity having a mortality of 80% or higher in a throughput of 0.1 mg/seedling.

Reference Test Example 18

Pest Control Test of Laodelphax striatella

(202) Wheat seedling roots forty eight hours after the dissemination of seeds were treated with a drug solution of the compound of the present invention at a predetermined concentration, which had been prepared so as to be a 10% acetone water. The drug was absorbed from the roots for 72 hours, and then ten second instar larvae of Laodelphax striatella were each released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Four days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(203) As a result, compounds P212 and 1-204 exhibited insecticidal activity having a mortality of 80% or higher in a throughput of 20 g/seedling.

(204) The results of Reference Test Examples 1, 3 and 18 are shown in the following Table.

(205) TABLE-US-00070 TABLE 55 Plutella Aphis Laodelphax xylostella gossypii striatella Reference (Reference (Reference (Reference Example Test Test Test Compound Example Example Example No. Ar Y R 1) 3) 18) P-212 6-chloro- H COCF3 100 100 100 3-pyridyl P-213 2-chloro- H COCF3 100 100 100 5-thiazolyl P-215 6-chloro- 5-Cl COCF3 100 80 75 3-pyridyl P-216 6-chloro- 5-F COCF3 100 95 100 3-pyridyl P-218 2-chloro- 5-Cl COCF3 100 60 5-thiazolyl P-219 2-chloro- 5-F COCF3 80 85 5-thiazolyl P-222 6-chloro- 4-Me COCF3 100 100 3-pyridyl P-223 6-chloro- 5-Me COCF3 75 75 3-pyridyl P-225 4-chloro- H COCF3 90 phenyl P-226 3-pyridyl H COCF3 60 100 P-227 6-chloro- H COCF3 100 100 100 5-fluoro- 3-pyridyl P-228 6-trifluoromethyl- H COCF3 30 95 100 3-pyridyl P-229 6-fluoro- H COCF3 100 100 100 3-pyridyl P-230 5,6-dichloro- H COCF3 100 100 3-pyridyl P-231 6-bromo-3- H COCF3 100 100 100 pyridyl P-232 6-chloro- 4-F COCF3 80 3-pyridyl P-233 6-chloro- 3-F COCF3 100 75 3-pyridyl P-234 6-chloro- H COCHCl2 100 100 100 3-pyridyl P-235 6-chloro- H COCCl3 100 95 75 3-pyridyl P-236 6-chloro- H COCH2Cl 100 3-pyridyl P-238 6-chloro- H COCHF2 100 100 100 3-pyridyl P-239 6-chloro- H COCF2Cl 100 100 100 3-pyridyI P-240 6-chloro- H COCHClBr 100 100 3-pyridyl P-241 6-chloro- H COCHBr2 100 100 3-pyridyl P-242 6-chloro- H COCF2CF3 100 100 100 3-pyridyl P-243 2-chloro- H COCF3 100 100 100 5-pyrimidinyl P-244 6-chloro- H COCH2Br 100 100 3-pyridyl 1-20 6-chloro- H CSCF3 100 100 100 3-pyridyl 1-21 6-chloro- H CSCHF2 80 100 100 3-pyridyl 1-22 6-chloro- H CSCF2C1 100 100 3-pyridyl 1-23 6-chloro- H CSCF2CF3 100 100 3-pyridyl 1-42 6-chloro- H C(NOMe)CF3 100 100 100 3-pyridyl 1-150 6-chloro- H C(NCH2CH2 100 100 80 3-pyridyl SMe)CF3 3-3 6-fluoro- H COCHF2 50 100 80 3-pyridyl 3-4 6-fluoro- H COCF2Cl 100 100 100 3-pyridyl 3-5 6-fluoro- H COCF2CF3 100 55 80 3-pyridyl 3-20 6-fluoro- H CSCF3 55 100 80 3-pyridyl 4-3 6-Bromo- H COCHF2 100 100 3-pyridyl 4-4 6-Bromo- H COCF2Cl 100 100 3-pyridyl 4-5 6-Bromo- H COCF2CF3 100 100 100 3-pyridyl 4-20 6-Bromo- H CSCF3 100 100 100 3-pyridyl 5-3 6Chloro- H COCHF2 100 100 5fluoro- 3pyridyl 5-4 6Chloro- H COCF2Cl 100 100 5fluoro- 3pyridyl 5-20 6Chloro- H CSCF3 100 100 5fluoro- 3pyridyl 6-3 2-Cl-5- H COCHF2 80 100 pyrimidinyl 6-4 2-Cl-5- H COCF3Cl 90 100 100 pyrimidinyl 102-2.sup. 6-chloro- 3-CN COCF3 10 100 100 3-pyridyl

(206) <Effects Against Insecticide Resistant Pests>

Reference Test Example 19

Pest Control Test of Nilaparvata lugens

(207) A rice seedling in pot culture was subjected to soil drench with a solution of the compound of Formula (I), which had been prepared so as to be a 10% acetone water. Three days after the treatment, ten second instar larvae of Nilaparvata lugens, which had been collected outdoors and proliferated indoors, were each released to the rice seedling. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Six days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. Test in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(208) Furthermore, for comparison, the test against a species of Nilaparvata lugens which is highly susceptible to imidacloprid was performed by the same method as described above, and the results thereof are shown in Table 45. As described in Table 45, Compound P212 and Compound 1-20 exhibited high insecticidal effects against susceptible species and drug resistant species of Nilaparvata lugens, and the death rates of larvae at 0.005 mg/seedling were (susceptible species) 100% and 100%, (resistant population I) 95% and 77% and (resistant population II) 100% and 85%, respectively. Meanwhile, the death rates of imidacloprid at 0.05 mg/seedling were (susceptible species) 100%, (resistant population I) 38% and (resistant population II) 69%, and the insecticidal effect thereof was also low even at a high dose. From the above results, it became obvious that Compound P212 and Compound 1-20 have high insecticidal effects even against Nilaparvata lugens resistance against imidacloprid.

(209) Further, for the origin of test pests, bugs collected outdoors from the Kumamoto prefecture (I) in 2007 and from the Fukuoka prefecture (II) in 2005 as resistant population of Nilaparvata lugens, and bugs collected from the Kagoshima prefecture and then successively reared indoors for a long time as the imidacloprid susceptible population of Nilaparvata lugens were used.

(210) TABLE-US-00071 TABLE 56 Insecticidal effects against Nilaparvata lugens (death rate %) Effects against Nilaparvata lugens Resistant Resistant Susceptible population population population I II six days six days six days Throughput after the after the after the (mg/seedling) treatment treatment treatment P212 0.05 100 100 100 0.005 100 95 100 1-20 0.01 95 100 100 0.005 100 77 85 Imidacloprid 0.05 100 38 69 0.01 100 39

(211) <Mixed Agent Test Example>

Test Example 1

Soil Irrigation Treatment Test of Laodelphax striatella

(212) A rice seedling in pot culture was subjected to soil drench treatment with a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 10% acetone water. After the rice seedling was left to stand for 3 days, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(213) In addition, when there was no synergistic effect, a theoretical value was calculated by the Colby's equation shown as follows, and the results are shown in the Table.
theoretical value (%)=100(AB)/100Colby's equation:

(214) (A: 100(mortality of larvae or adults when treated only with Compound P212 or Compound 1-20)

(215) B: 100(mortality of larvae or adults when treated only with each of imidacloprid, fipronil, chlorantraniliprole, spinosad, clothianidin, dinotefuran, sulfoxaflor, pymetrozine, thiamethoxam, flupyradifurone and cycloxaprid))

(216) Method for Judging Synergistic Effects

(217) When the mortality against Laodelphax striatella in the case of a mixture with another agent exceeded the theoretical value by the Colby's equation, a synergistic effect was judged to be present.

(218) It was demonstrated that mixed agents of the insecticides of imidacloprid, fipronil, chlorantraniliprole, spinosad, clothianidin, dinotefuran, sulfoxaflor, pymetrozine, thiamethoxam, flupyradifurone and cycoxaprid, which were provided and tested as Compound P212, all show a mortality of larvae or adults, exceed the theoretical value and have synergistic effects.

(219) In addition, it was demonstrated that mixed agents of the insecticides of imidacloprid and fipronil, which were provided and tested as Compound 1-20, all show a mortality of larvae or adults, exceed the theoretical value and have synergistic effects.

(220) Furthermore, it was demonstrated that mixed agents of the fungicides of probenazole, isotianil, tiadinil and orysastrobin, which were provided and tested as Compound P212, all exhibit insecticidal effect equal to or higher than the insecticidal effect when treated with Compound P212 alone and may be mixed and treated with a fungicide. Likewise, it was demonstrated that mixed agents of the fungicide of probenazole, which was provided and tested as Compound 1-20, exhibit insecticidal effect equal to or higher than the insecticidal effect when treated with Compound 1-20 alone and may be mixed and treated with a fungicide.

(221) <Example of Mixed Agent with Insecticide>

(222) TABLE-US-00072 TABLE 57 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 39 Imidacloprid 0.005 0 70 Fipronil 0.005 26 65 Chlorantraniliprole 0.05 9 60 Spinosad 0.5 0 62

(223) TABLE-US-00073 TABLE 58 Theoretical value (%) by Colby's equation Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 39 Imidacloprid 0.005 0 39 Fipronil 0.005 26 55 Chlorantraniliprole 0.05 9 44 Spinosad 0.5 0 39

(224) TABLE-US-00074 TABLE 59 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 18 Clothianidin 0.005 23 56 Dinotefuran 0.005 0 30 Sulfoxaflor 0.005 1 63 Pymetrozine 0.05 15 89

(225) TABLE-US-00075 TABLE 60 Theoretical value (%) by Colby's equation Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 18 Clothianidin 0.005 23 37 Dinotefuran 0.005 0 18 Sulfoxaflor 0.005 1 19 Pymetrozine 0.05 15 30

(226) TABLE-US-00076 TABLE 61 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 14 Thiamethoxam 0.01 23 45

(227) TABLE-US-00077 TABLE 62 Theoretical value (%) by Colby's equation Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 14 Thiamethoxam 0.01 23 34

(228) TABLE-US-00078 TABLE 63 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 45 Flupyradifurone 0.01 5 85

(229) TABLE-US-00079 TABLE 64 Theoretical value (%) by Colby's equation Rate mg/ Compoud P212 Insecticide name Seedling 0 0.005 0 45 Flupyradifurone 0.01 5 48

(230) TABLE-US-00080 TABLE 65 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate mg/ Compound 1-20 Insecticide name Seedling 0 0.005 0 12 Imidacloprid 0.005 0 74 Fipronil 0.001 0 80

(231) TABLE-US-00081 TABLE 66 Theoretical value (%) by Colby's equation Rate Compound 1-20 Insecticide name mg/Seedling 0 0.005 0 12 Imidacloprid 0.005 0 12 Fibronil 0.001 0 12

(232) TABLE-US-00082 TABLE 67 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 0 Cycloxaprid 0.005 0 7

(233) TABLE-US-00083 TABLE 68 Theoretical value (%) by Colby's equation Rate mg/ Compound P212 Insecticide name Seedling 0 0.005 0 0 Cycloxaprid 0.005 0 0

(234) TABLE-US-00084 TABLE 69 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate Compound Compound 1- mg/ P212 20 Fungicide name Seedling 0 0.005 0 0.005 0 39 0 8 Probenazole 0.5 9 59 9 65

(235) TABLE-US-00085 TABLE 70 Theoretical value (%) by Colby's equation Rate Compound Compound mg/ P212 1-20 Fungicide name Seedling 0 0.005 0 0.005 0 39 0 8 Probenazole 0.5 9 44 9 16

(236) TABLE-US-00086 TABLE 71 Mortality (%) of single agent and mixed agent against Laodelphax striatella Rate Compound P212 Fungicide name mg/Seedling 0 0.005 0 19 Isotianil 0.5 5 30 Tiadinil 0.5 8 30 Orysastrobin 0.5 4 70

(237) TABLE-US-00087 TABLE 72 Theoretical value (%) by Colby's equation Rate Compound P212 Fungicide name mg/Seedling 0 0.005 0 19 Isotianil 0.5 5 23 Tiadinil 0.5 8 25 Orysastrobin 0.5 4 22

Test Example 2

Foliar Treatment Test Against Laodelphax striatella

(238) A drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was foliar sprayed to a rice seedling in pot culture. After an air drying process, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(239) Further, when there was no synergistic effect, a theoretical value was calculated by the Colby's equation shown as follows, and the results are shown in the Table.
Theoretical value (%)=100(AB)/100Colby's equation:

(240) (A: 100(mortality of larvae or adults when treated only with Compound P212 or Compound 1-20)

(241) B: 100(mortality of larvae or adults when treated only with etofenprox or silafluofen))

(242) Method for Judging Synergistic Effects

(243) When the mortality against Laodelphax striatella in the case of a mixture with another agent exceeded the theoretical value by the Colby's equation, a synergistic effect was judged to be present.

(244) It was demonstrated that mixed agents of the insecticides of etofenprox and silafluofen, which were provided and tested as Compound P212 or Compound 1-20, all show a mortality of larvae or adults approximately equal to the theoretical value, and may be mixed with the insecticide even in a foliar treatment-like usage.

(245) TABLE-US-00088 TABLE 73 Mortality (%) of single agent and mixed agent against Laodelphax s striatella Compound Compound Insecticide Rate P212 1-20 name (ppm) 0 0.625 0.625 0 95 90 Etofenprox 10 30 90 95 Silafluofen 5 55 100 100

(246) TABLE-US-00089 TABLE 74 Theoretical value (%) by Colby's equation Compound Compound Insecticide Rate P212 1-20 name (ppm) 0 0.625 0.625 0 95 90 Etofenprox 10 30 97 93 Silafluofen 5 55 98 95

Test Example 3

Pest Control Test of Aphis gossypii

(247) A leaf disk having a diameter of 2.0 cm was cut out from a cucumber in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed thereto. After an air drying process, first instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(248) In addition, when there was no synergistic effect, a theoretical value was calculated by the Colby's equation shown as follows, and the results are shown in the Table.
Theoretical value (%)=100(AB)/100Colby's equation:

(249) (A: 100(mortality of larvae or adults when treated only with Compound P212 or Compound 1-20)

(250) B: 100(mortality of larvae or adults when treated only with afidopyropen)

(251) Method for Judging Synergistic Effects

(252) When the mortality against Aphis gossypii in the case of a mixture with another agent exceeded the theoretical value by the Colby's equation, a synergistic effect was judged to be present.

(253) It was demonstrated that mixed agents of compounds of Formula (II), which were provided and tested as Compound P212 or Compound 1-20, all show a mortality of larvae or adults, exceed the theoretical value and have synergistic effects.

(254) TABLE-US-00090 TABLE 75 Mortality (%) of single agent and mixed agent against Aphis gossypii Insecticide Rate Compound P212 Compound 1-20 name ppm 0 0.313 0 0.625 0 45 0 19 Afidopyropen 0.002 25 70 25 40

(255) TABLE-US-00091 TABLE 76 Theoretical value (%) by Colby's equation Insecticide Rate Compound P212 Compound 1-20 name ppm 0 0.313 0 0.625 0 45 0 19 Afidopyropen 0.002 25 59 25 39

Test Example 4

Pest Control Test of Plutella xylostella

(256) A leaf disk having a diameter of 5.0 cm was cut out from a cabbage in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed thereto. After an air drying process, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the mortality of larvae was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(257) Furthermore, when there was no synergistic effect, a theoretical value was calculated by the Colby's equation shown as follows, and the results are shown in the Table.
Theoretical value (%)=100(AB)/100Colby's equation:

(258) (A: 100(mortality of larvae or adults when treated with only Compound P212)

(259) B: 100(mortality of larvae or adults when treated with only flometoquin, spinosad, fipronil, chlorantraniliprole, 1-((6-chloropyridin-3-yl)methyl)-4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidin-1-ium-2-olate, or afidcpyropen))

(260) Method for Judging Synergistic Effects

(261) When the mortality against Plutella xylostella in the case of a mixture with another agent exceeded the theoretical value by the Colby's equation, a synergistic effect was judged to be present.

(262) It was demonstrated that a mixed agent of the insecticide of flometoquin, which was provided and tested, with Compound P212, shows a death rate of larvae or adults, exceeds the theoretical value and has synergistic effects.

(263) TABLE-US-00092 TABLE 77 Mortality (%) of single agent and mixed agent against Plutella xylostella Rate Compound P212 Insecticide name ppm 0 1.25 0 0 Flometoquin 0.313 0 30

(264) TABLE-US-00093 TABLE 78 Theoretical value (%) by Colby's equation Insecticide Rate Compound P212 name ppm 0 1.25 0 0 Flometoquin 0.313 0 0

(265) TABLE-US-00094 TABLE 79 Mortality (%) of single agent and mixed agent against Plutella xylostella Compound P212 Rate ppm Insecticide name 0 1.0 0 40 Afidopyropen Rate 10 20 70 Spinosad ppm 0.01 11 70

(266) TABLE-US-00095 TABLE 80 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 1.0 0 40 Afidopyropen Rate 10 20 52 Spinosad ppm 0.01 11 45

(267) TABLE-US-00096 TABLE 81 Mortality (%) of single agent and mixed agent against Plutella xylostella Compound P212 Rate ppm Insecticide name 0 1.0 0 30 Afidopyropen Rate 5 0 80 ppm

(268) TABLE-US-00097 TABLE 82 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 1.0 0 30 Afidopyropen Rate 5 0 30 ppm

(269) TABLE-US-00098 TABLE 83 Mortality (%) of single agent and mixed agent against Plutella xylostella Compound P212 Rate ppm Insecticide name 0 2.0 0 60 Fipronil Rate 0.04 50 100 Chlorantraniliprole ppm 0.002 60 100

(270) TABLE-US-00099 TABLE 84 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 2.0 0 60 Fipronil Rate 0.04 50 80 Chlorantraniliprole ppm 0.002 60 84

(271) TABLE-US-00100 TABLE 85 Mortality (%) of single agent and mixed agent against Plutella xylostella Compound P212 Rate ppm Insecticide name 0 2.0 0 50 1-((6- Rate 1 30 70 chloropyridin- ppm 3-yl)methyl)-4- oxo-3-phenyl- 4H-pyrido[1,2- a]pyrimidin-1- ium-2-olate Afidopyropen 5 0 100

(272) TABLE-US-00101 TABLE 86 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 2.0 0 50 1-((6- Rate 1 30 65 chloropyridin- ppm 3-yl)methyl)-4- oxo-3-phenyl- 4H-pyrido[1,2- a]pyrimidin-1- ium-2-olate Afidopyropen 5 0 50

Test Example 5

Pest Control Test of Spodoptera litura

(273) A leaf disk having a diameter of 5.0 cm was cut out from a cabbage in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed thereto. After an air drying process, third instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the larvae mortality was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(274) Furthermore, a theoretical value for the case of no synergistic effect was calculated using Colby's equation given below, and the results are shown in the tables.
Theoretical value (%)=100(AB)/100Colby's equation:

(275) (A: 100(mortality of larvae or adults when treated only with Compound P212)

(276) B: 100(mortality of larvae or adults when treated with only the insecticide chlorantraniliprole, emamectin benzoate, flometoquin, or afidopyropen))

(277) Method for Judging Synergistic Effects

(278) When the mortality against Spodoptera litura in the case of a mixture with another agent exceeded the theoretical value given by Colby's equation, a synergistic effect was judged to be present.

(279) It was demonstrated that a mixed agent of the insecticide chlorantraniliprole, emamectin benzoate, flometoquin, or afidopyropen tested with Compound P212 shows a mortality for larvae or adults in excess of the theoretical value and has synergistic effects.

(280) TABLE-US-00102 TABLE 87 Mortality (%) of single agent and mixed agent against Spodoptera litura (1) Compound P212 Rate ppm Insecticide name 0 20 0 40 Afidopyropen Rate 10 0 80 ppm

(281) TABLE-US-00103 TABLE 88 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 20 0 40 Afidopyropen Rate 10 0 40 ppm

(282) TABLE-US-00104 TABLE 89 Mortality (%) of single agent and mixed agent against Spodoptera litura (2) Compound P212 Rate ppm Insecticide name 0 20 0 10 Chlorantraniliprole Rate 0.02 20 30 Emamectin benzoate ppm 0.02 0 20

(283) TABLE-US-00105 TABLE 90 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 20 0 10 Chlorantraniliprole Rate 0.02 20 28 Emamectin benzoate ppm 0.02 0 10

(284) TABLE-US-00106 TABLE 91 Mortality (%) of single agent and mixed agent against Spodoptera litura (3) Compound P212 Rate ppm Insecticide name 0 50 0 10 Flometoquin Rate 5 10 20 Afidopyropen ppm 5 0 50

(285) TABLE-US-00107 TABLE 92 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 50 0 10 Flometoquin Rate 5 10 19 Afidopyropen ppm 5 0 10

Test Example 6

Pest control test of Frankliniella occidentalis

(286) A leaf disk having a diameter of 2.8 cm was cut out from the common bean in pot culture, and a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 50% acetone water (0.05% Tween20 available), was sprayed thereto. After an air drying process, first instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Three days after the release, the larvae were observed for survival or death, and the larvae mortality was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(287) Furthermore, a theoretical value for the case of no synergistic effect was calculated using Colby's equation given below, and the results are shown in the table.
Theoretical value (%)=100(AB)/100Colby's equation:

(288) (A: 100(mortality of larvae or adults when treated only with Compound P212)

(289) B: 100(mortality of larvae or adults when treated with only the insecticide imidacloprid, dinotefuran, or acetamiprid))

(290) Method for Judging Synergistic Effects

(291) When the mortality against Frankliniella occidentalis in the case of a mixture with another agent exceeded the theoretical value given by Colby's equation, a synergistic effect was judged to be present.

(292) It was demonstrated that a mixed agent of the insecticide imidacloprid or dinotefuran tested with Compound P212 shows a mortality for larvae or adults in excess of the theoretical value and has synergistic effects.

(293) TABLE-US-00108 TABLE 93 Mortality (%) of single agent and mixed agent against Frankliniella occidentalis (1) Compound P212 Rate ppm Insecticide name 0 10 0 69 Imidacloprid Rate 20 69 94 ppm

(294) TABLE-US-00109 TABLE 94 Theoretical value (%) by Colby's equation Compound P212 Rate ppm Insecticide name 0 10 0 69 Imidacloprid Rate 20 69 90 ppm

(295) TABLE-US-00110 TABLE 95 Mortality (%) of single agent and mixed agent against Frankliniella occidentalis (2) Compound P212 Rate ppm Insecticide name 0 20 0 70 Dinotefuran Rate 5 35 85 ppm

(296) TABLE-US-00111 TABLE 96 Theoretical value (%) by Colby' s equation Compound P212 Rate ppm Insecticide name 0 20 0 70 Dinotefuran Rate 5 35 81 ppm

Test Example 7

Soil Irrigation Treatment Test on Chilo suppressalis

(297) Rice seedlings in pot culture were submitted to a soil irrigation treatment with a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 10% acetone water. After standing for 3 days, second instar larvae were released thereto. This was followed by standing in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Six days after the release, the larvae were observed for survival or death, and the larvae mortality was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(298) Furthermore, a theoretical value for the case of no synergistic effect was calculated using Colby's equation given below, and the results are shown in the table.
Theoretical value (%)=100(AB)/100Colby's equation:

(299) (A: 100(mortality of larvae or adults when treated only with Compound P212)

(300) B: 100(mortality of larvae or adults when treated with only the insecticide fipronil, cyantraniliprole or spinosad))

(301) Method for Judging Synergistic Effects

(302) When the insecticidal effect (table) against Chilo suppressalis in the case of a mixture with another agent exceeded the theoretical value given by Colby's equation, a synergistic effect was judged to be present.

(303) It was demonstrated that a mixed agent of the insecticide fipronil, cyantraniliprole or spinosad tested with Compound P212 shows a mortality for larvae or adults in excess of the theoretical value in both cases and has synergistic effects.

(304) TABLE-US-00112 TABLE 97 Mortality (%) of single agent and mixed agent against Chilo suppressalis (1) Compound P212 Rate mg/seedling Insecticide name 0 0.01 0 33 Cyantraniliprole Rate 0.005 83 100 mg/seedling

(305) TABLE-US-00113 TABLE 98 Theoretical value (%) by Colby's equation Compound P212 Rate mg/seedling Insecticide name 0 0.01 0 33 Cyantraniliprole Rate 0.005 83 89 mg/seedling

(306) TABLE-US-00114 TABLE 99 Mortality (%) of single agent and mixed agent against Chilo suppressalis (2) Compound P212 Rate mg/seedling Insecticide name 0 0.002 0 40 Fipronil Rate 0.0005 40 80 Chlorantraniliprole mg/seedling 0.0005 60 80 Spinosad 0.002 80 100

(307) TABLE-US-00115 TABLE 100 Theoretical value (%) by Colby's equation Compound P212 Rate mg/seedling Insecticide name 0 0.002 0 40 Fipronil Rate 0.0005 40 64 Chlorantraniliprole mg/seedling 0.0005 60 76 Spinosad 0.002 80 88

Test Example 8

Soil Irrigation Treatment Test on Naranga aenescens

(308) Rice seedlings in pot culture were subjected to a soil irrigation treatment with a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared so as to be a 10% acetone water. After standing for 3 days, first instar larvae were released thereto. This was followed by standing in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Five days after the release, the larvae were observed for survival or death, and the larvae mortality was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(309) Furthermore, a theoretical value for the case of no synergistic effect was calculated using Colby's equation given below, and the results are shown in the table.
Theoretical value (%)=100(AB)/100Colby's equation:

(310) (A: 100(mortality of larvae or adults when treated only with Compound P212)

(311) B: 100(mortality of larvae or adults when treated with only the insecticide spinosad or fipronil))

(312) Method for Judging Synergistic Effects

(313) When the mortality against Naranga aenescens in the case of a mixture with another agent exceeded the theoretical value given by Colby's equation, a synergistic effect was judged to be present.

(314) It was demonstrated that a mixed agent of the insecticide spinosad or fipronil tested with Compound P212 shows a mortality for larvae or adults in excess of the theoretical value in all cases and has synergistic effects.

(315) TABLE-US-00116 TABLE 101 Mortality (%) of single agent and mixed agent against Naranga aenescens Compound P212 Rate mg/seedling Insecticide name 0 0.01 0 60 Spinosad Rate 0.005 40 100 Fipronil mg/seedling 0.01 20 80

(316) TABLE-US-00117 TABLE 102 Theoretical value (%) by Colby's equation Compound P212 Rate mg/seedling Insecticide name 0 0.01 0 60 Spinosad Rate 0.005 40 76 Fipronil mg/seedling 0.01 20 68

Test Example 9

Test on Callosobruchus Chinensis

(317) A compound of Formula (I) and the insecticide indicated below, prepared in predetermined concentrations using acetone, were separately topically applied to the back of the same adult Callosobruchus chinensis. The Callosobruchus chinensis was then introduced into a plastic cup and held in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. One day after the release, the insects were observed for survival or death, and the insect mortality was calculated by the following equation. The test was performed in duplicate.
Insect mortality (%)={number of dead insects/(number of survived insects+number of dead insects)}100

(318) Furthermore, a theoretical value for the case of no synergistic effect was calculated using Colby's equation given below, and the results are shown in the table.
Theoretical value (%)=100(AB)/100Colby's equation:

(319) (A: 100(insect mortality for treatment with only Compound P212)

(320) B: 100(insect mortality for treatment with only the insecticide fipronil or imidacloprid))

(321) Method for Judging Synergistic Effects

(322) When the mortality against Callosobruchus chinensis in the case of a mixture with another agent exceeded the theoretical value given by Colby's equation, a synergistic effect was judged to be present.

(323) It was demonstrated that co-treatment with the insecticide fipronil or imidacloprid tested with Compound P212 shows an insect mortality in excess of the theoretical value in both cases and has synergistic effects.

(324) TABLE-US-00118 TABLE 103 Mortality (%) of single agent and mixed agent against Callosobruchus chinensis Compound P212 Rate ng/head Insecticide name 0 0.2 0 20 Fipronil Rate 0.2 0 36 Imidacloprid ng/head 0.2 40 60

(325) TABLE-US-00119 TABLE 104 Theoretical value (%) by Colby's equation Compound P212 Rate ng/head Insecticide name 0 0.2 0 20 Fipronil Rate 0.2 0 20 Imidacloprid ng/head 0.2 40 52

Test Example 10

Pest Control Test of Rice Blast

(326) A rice seedling in pot culture was subjected to soil irrigation treatment with a drug solution of the compound of Formula (I) at a predetermined concentration, or a drug solution of a mixture of a compound of Formula (I) and an insecticide as indicated below at a predetermined concentration, which had been prepared with a 10% acetone water. Three days after the treatment, a spore suspension (210.sup.5 ea/mL, 0.05% Tween available) of rice blast bacteria was sprayed and inoculated thereto, and the rice seedling was placed in a moist chamber for 24 hours to promote infection. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Seven days after the inoculation, the number of lesions was measured, and the preventive value was calculated by the following equation. The test was performed in triplicate.
Preventive value={(number of lesions in a zone without treatmentnumber of lesions in a zone with treatment)/(number of lesions without treatment)}100

(327) As a result, it was demonstrated that in a throughput of probenazole at 0.125 mg/seedling, any one mixed agent of Compound P212 and Compound 1-20 exhibits insecticidal effect equal to the insecticidal effect when treated with probenazole alone and may be mixed and treated with a fungicide.

(328) TABLE-US-00120 TABLE 105 Compound Compound P212 1-20 Rate mg/seedling Insecticide name 0 2.5 0 2.5 0 3.3 0 52.5 Probenazole Rate 0.125 96.7 93.4 96.7 91.8 mg/seedling

Test Example 11

Test of Rice Blast Control Foliar Treatment

(329) Rice seedlings were treated by foliar application with a drug solution of the compound of Formula (I), or a drug solution of a mixture of a compound of Formula (I) and the fungicide indicated below, prepared in a predetermined concentration with 10% acetone water. After the treatment, a rice blast spore suspension (1.510.sup.5 ea/mL, 0.05% Tween available) was sprayed and inoculated thereto followed by holding in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. Fourteen days after the inoculation, the number of lesions was measured, and the preventive value was calculated by the following equation. The test was performed in triplicate.
Preventive value={(number of lesions in a zone without treatmentnumber of lesions in a zone with treatment)/(number of lesions in a zone without treatment)}100

(330) As a result, it was demonstrated that at a treatment concentration of 0.5 ppm using tiadinil, isotianil, orysastrobin, tricyclazole, diclocymet, tebufloquin, azoxystrobin or kasugamycin, the mixed agent with Compound P212 also exhibits a fungicidal effect equal to that for treatment with tiadinil, isotianil, orysastrobin, tricyclazole, diclocymet, tebufloquin, azoxystrobin or kasugamycin alone and a mixed treatment with a fungicide is therefore possible.

(331) TABLE-US-00121 TABLE 106 (Rice blast test 1) Compound P212 Rate ppm Fungicide name 0 50 0 4 Tiadinil Rate 0.5 0 18 Isotianil ppm 0.5 66 72

(332) TABLE-US-00122 TABLE 107 (Rice blast test 2) Compound P212 Rate ppm Fungicide name 0 50 0 16 Orysastrobin Rate 0.5 20 91 Tricyclazole ppm 0.5 72 92 Diclocymet 0.5 8 52 Tebufloquin 0.5 48 72

(333) TABLE-US-00123 TABLE 108 (Rice blast test 3) Compound P212 Rate ppm Fungicide name 0 50 0 0 Azoxystrobin Rate 0.5 37 35 Kasugamycin ppm 0.5 0 37

Test Example 12

Test of Control of Rice Sheath Blight Rhizoctonia solani

(334) Six weeks after planting, rice seedlings were subjected to foliar spray treatment with a drug solution of the compound of Formula (I), or a drug solution of a mixture of a compound of Formula (I) and a fungicide as indicated below, prepared in a predetermined concentration with 10% acetone water. After an air drying process, a plug of growing Rhizoctonia solani (1.0 cm.sup.2 agar square each) was allowed to stand at the base of the rice. This was followed by holding in a thermostatic chamber (30 C. day-25 C. night, 16 hours of light period-8 hours of dark period). Six days after the inoculation, the lesion height was measured, and the preventive value was calculated by the following equation. The test was performed in duplicate.
Preventive value={(lesion height in a zone without treatmentlesion height in a zone with treatment)/(lesion height in a zone without treatment)}100

(335) As a result, it was demonstrated that, at a treatment concentration of 5 ppm using thifluzamide, furametpyr, pencycuron, azoxystrobin, simeconazole, validamycin, or orysastrobin, the mixed agent with 50 ppm Compound P212 presented the same fungicidal effect as for treatment with thifluzamide, furametpyr, pencycuron, azoxystrobin, simeconazole, validamycin, or orysastrobin alone, and mixed treatment with a fungicide is therefore possible.

(336) TABLE-US-00124 TABLE 109 (Sheath blight test 1) Compound P212 Rate ppm Fungicide name 0 50 0 14 Thifluzamide Rate 5 92 97 Furametpyr ppm 5 77 94 Pencycuron 5 69 77

(337) TABLE-US-00125 TABLE 110 (Sheath blight test 2) Compound P212 Rate ng/head 0 50 Fungicide name 0 9 Azoxystrobin Rate 5 95 100 Simeconazole ppm 5 5 24 Validamycin 5 32 74 Orysastrobin 5 72 59

Test Example 13

Test with Laodelphax striatellus by Treatment During the Vegetative Phase

(338) Rice was planted in nursery boxes and emergence was carried out for three days a 30 C. followed by transfer of the nursery boxes to a glass greenhouse at 25 C. During the vegetative phase five days after planting, the nursery boxes were treated with a prescribed amount of a mixed granule of 0.24 mg/mg probenazole (24%) and 0.02 mg/mg Compound P212 (2%). The rice seedlings were transplanted to 1/5000a Wagner pots 22 days after planting and were grown in a greenhouse at 25 C. Second instar larvae of Laodelphax striatellus were released at 13, 26, and 38 days post-transplantation to the Wagner pots; this was followed by holding in a glass greenhouse at 25 C. Five days after the release, the larvae were observed for survival or death, and the larvae mortality was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(339) According to the results, it was shown that the mixed granule of probenazole and Compound P212 presented a high insecticidal effect of 100% mortality and exhibited control at a practical level.

Test Example 14

Test with Laodelphax striatellus by Soil Irrigation Treatment

(340) Rice seedlings in pot cultivation were subjected to a soil irrigation treatment with a drug solution of a compound of Formula (I) or a drug solution of a mixture of a compound of Formula (I) and a paddy herbicide as indicated below, prepared in predetermined concentrations so as to be a 10% acetone water. After standing for three days, second instar larvae were released thereto. Thereafter, the larvae were left to stand in a thermostatic chamber (16 hours of light period-8 hours of dark period) at 25 C. five days after the release, the larvae were observed for survival or death, and the larvae mortality was calculated by the following equation. The test was performed in duplicate.
Mortality of larvae (%)={number of dead larvae/(number of survived larvae+number of dead larvae)}100

(341) The mixed agent of Imazosulfuron, cafenstrole, cyhalofop-butyl, daimuron and pyrazolate tested with the Compound P212 was shown in all instances to exhibit an insecticidal effect at least equal to that for treatment with Compound P212 by itself, and a mixed treatment with a herbicide is thus possible.

(342) TABLE-US-00126 TABLE 111 Compound P212 Rate mg/seedling Herbicide name 0 0.005 0.01 0 0 100 Imazosulfuron Rate 0.05 0 0 100 Cafenstrole mg/seedling 0.05 0 0 100 Cyhalofop- 0.05 0 0 100 butyl Daimuron 0.05 0 0 100 Pyrazolate 0.05 0 0 100

Test Example 15

Test of the Control of Haemaphysalis longicornis

(343) A capsule with a diameter of 2 cm and a height of 2 cm was attached to the dorsal surface of a mouse. A compound of Formula (I), ivermectin, moxidectin, permethrin, amitraz, fipronil, spinetram and the mixture of the compound of Formula (I) and each insecticide were dissolved in ethanol at the concentrations given in Table O, and each of these was dripped onto the surface of a mouse body within a capsule. After thorough drying, eight Haemaphysalis longicornis nymphs were released and the top of the capsule was sealed with a lid. The mouse was kept in a cage at 25 C. using a 12-hour light period and a 12-hour dark period. Five days after the release, the capsule was removed and the number of surviving and dead nymphs and the number of engorged individuals were counted and the insect mortality and agonal rate was calculated by the following equation.
Insect mortality and agonal rate (%)={number of dead and agonal insects/(number of survived insects+number of dead and agonal insects)}100

(344) The results showed that, at a rate of 0.009 g of ivermectin or moxidectin, the mixed agent of either with Compound P212 also gave a tick control effect that was the same as treatment with ivermectin, moxidectin, permethrin, amitraz, fipronil and spinetram alone and mixed treatment with ivermectin, moxidectin, permethrin, amitraz, fipronil and spinetram is thus possible.

(345) TABLE-US-00127 TABLE 112 Mortality (%) of single agent and mixed agent against Haemaphysalis longicornis(1) Compound P212 Rate g Insecticide name 0 1.18 0 53 Ivermectin Rate 0.009 3 53 Moxidectin g 0.009 6 44

(346) TABLE-US-00128 TABLE 113 Mortality (%) of single agent and mixed agent against Haemaphysalis longicornis(2) Compound P212 Rate g Insecticide name 0 1.18 0 60 Amitraz Rate 10.38 41 90 Permethrin g 9.5 71 86

(347) TABLE-US-00129 TABLE 114 Theoretical value (%) by Colby's equation Compound P212 Rate g Insecticide name 0 1.18 0 60 Amitraz Rate 0.38 41 77 Permethrin g 9.5 71 88

(348) TABLE-US-00130 TABLE 115 Mortality (%) of single agent and mixed agent against Haemaphysalis longicornis(3) Compound P212 Rate g Insecticide name 0 1.18 0 36 fipronil Rate 0.38 78 93 spinetoram g 0.38 6 22

(349) TABLE-US-00131 TABLE 116 Theoretical value (%) by Colby's equation Compound P212 Rate g Insecticide name 0 1.18 0 38 fipronil Rate 0.38 78 86 spinetoram g 0.38 6 41

(350) TABLE-US-00132 TABLE 117 Mortality (%) of single agent and mixed agent against Haemaphysalis longicornis(4) Compound P212 Rate g Insecticide name 0 1.18 0 18 pyriproxyfen Rate 0.0475 2 44 spinosad g 1.9 2.5 43

(351) TABLE-US-00133 TABLE 118 Theoretical value (%) by Colby's equation Compound P212 Rate g Insecticide name 0 1.18 0 18 pyriproxyfen Rate 0.0475 2 20 spinosad g 1.9 2.5 20

(352) TABLE-US-00134 TABLE 119 Mortality (%) of single agent and mixed agent against Haemaphysalis longicornis(5) Compound P212 Rate g Insecticide name 0 1.18 0 23 imidacloprid Rate 1.9 7.7 60 diriotefuran g 1.9 0

(353) TABLE-US-00135 TABLE 120 Theoretical value (%) by Colby's equation Compound P212 Rate g Insecticide name 0 1.18 0 23 imidacloprid Rate 1.9 7.7 32 dinotefuran g 1.9 0 25