巴西专利BR112016021257B1 2- (2,4-difluorophenyl-1,1-diflúor-1- (5-substituted-pyridin-2-yl) -3- (1h-tetrazol-1-yl) propan-2-o

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专利摘要:
2- (2,4-DIFLUOROFENIL-1,1-DIFLÚOR-1- (5-REPLACED-PYRIDIN-2-IL) -3- (1H-TETRAZOL-1-yl) PROPAN-2-ÓIS AND PROCESSES FOR PREPARATION OF The same are provided herein 2- (2,4-difluorophenyl) -1,1-difluor-1- (5-substituted-pyridin-2-yl) -3- (1H-tetrazol-1-yl) propan- 2-them and processes for their preparations.
公开号:BR112016021257B1
申请号:R112016021257-6
申请日:2015-03-19
公开日:2021-03-02
发明作者:William J. Hoekstra；Daniel Knueppel；Jim Renga；Greg WHITEKER；Michael T. Sullenberger
申请人:Viamet Pharmaceuticals (NC), Inc.；
IPC主号:

专利说明:

CROSS REFERENCE TO RELATED REQUESTS
[001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 61 / 955,661, filed March 19, 2014, which is expressly incorporated by reference herein herein. FIELD
[002] 2- (2,4-Difluorophenyl) -1,1-difluoro-1- (5-substituted-pyridin-2-yl) -3- (1H-tetrazol-1-yl) propan are provided herein -2-loops and processes for their preparation. BACKGROUND
[003] U.S. Patent applications 13 / 527,387, 13 / 527,426 and 13 / 528,283 describe inter alia certain metalloenzyme inhibiting compounds and their uses as fungicides. The description of each order is expressly incorporated by reference here in the present. Each of these patents describes the various ways to generate metalloenzyme inhibiting fungicides. It may be advantageous to provide more direct and efficient methods for the preparation of metalloenzyme inhibiting fungicides and related compounds, for example, through the use of reagents and / or chemical intermediates that provide improved time and cost efficiency. DESCRIPTION SUMMARY
[004] 2- (2,4-Difluorophenyl) -1,1-difluoro-1- (5-substituted-pyridin-2-yl) -3- (1H-tetrazol-1-yl) propan are provided herein -2-them and processes for their preparation. In one embodiment, provided herein, there is a process for the preparation of a compound of Formula IV:
characterized by the fact that R2 is selected from -CO2Et, -C (O) Me, -C (O) Ph, or -SO2 (4-MePh), which comprises contacting III with R2-CN.

[005] In another embodiment, III can be prepared by contacting II with sodium azide and a solvent.

[006] In another embodiment, II can be prepared by contacting I with trimethylsulfoxonium iodide and a base.

[007] In another embodiment, VI can be prepared by contacting compounds of Formula IV m that R2 is -CO2Et, with sodium hydroxide and by contacting the mixture of IV and sodium hydroxide with hydrochloric acid.

[008] In another embodiment, VI can be prepared by contacting compounds of Formula IV in which R2 is one of -C (O) Me and -C (O) Ph, with a base and a solvent.
[009] In another embodiment, VI can be prepared by contacting compounds of Formula IV, where R2 is -SO2 (4-MePh), with Zn and an acid.
[0010] The term "cyan" refers to the -C ^ N substituent.
[0011] The term "hydroxyl" refers to the -OH substituent.
[0012] The term "amino" refers to the -NH2 substituent.
[0013] The term "alkylamino" refers to -N (H) -R substituent.
[0014] The term "dialkylamino" refers to the substituent -NR2.
[0015] The term "halogen" or "halo" refers to one or more halogen atoms, defined as F, Cl, Br, and I.
[0016] The term "nitro" refers to the -NO2 substituent.
[0017] The term "Lewis acid" refers to any substance that is an electron pair acceptor.
[0018] The term "organometallic" refers to an organic compound containing a metal, especially a compound characterized by the fact that a metal atom is bonded directly to a carbon atom.
[0019] Throughout the description, references to compounds of Formula V, IV, III, and II are read as well as including isomers and optical salts. Specifically, when compounds of Formula V, IV, III, and II contain a branched chain alkyl group, it is understood that such compounds include optical isomers and racemates thereof. Exemplary salts can include: hydrochloride, hydrobromide, iodate and the like. In addition, compounds of Formula V, IV, III, and II can include tautomeric forms.
[0020] Certain compounds described in this document may exist as one or more isomers. It will be realized by those skilled in the art that an isomer may be more active than others. The structures described in the present description below are in a geometric shape for clarity only, but are intended to represent all geometric and tautomeric shapes of the molecule.
[0021] The modalities described above are intended merely to be exemplary, and those skilled in the art will recognize, or be able to verify using, no more than routine experimentation, numerous equivalents of specific compounds, materials, and procedures. All such equivalents are considered to be within the scope of the invention and are covered by the appended claims. DETAILED DESCRIPTION
[0022] 2- (2,4-Difluorophenyl) -1,1-diflúor-1- (5-substituted-pyridin-2-yl) - 3- (1H-tetrazol-1-yl) propan-2-os provided here at present, 4 - ((6- (2- (2,4-difluorophenyl) -1,1-difluor-2-oxoethyl) pyridin-3-yl) oxy) benzonitrile can be prepared, as shown in Examples 1- 7. Example 1: Preparation of 4 - ((6 - ((2- (2,4-difluorophenyl) oxiran-2-yl) difluoromethyl) pyridin-3-yl) oxy) benzonitrile

[0023] To a magnetically stirred solution of trimethylsulfoxonium iodide (2.67 g, 12.11 mmols) in dry THF / DMSO (1: 1, 39 mL each), was added sodium hydride (0.485 g, 12.11 mmols) under an atmosphere of N2. The reaction mixture was stirred at room temperature (rt) for 1 hour, then cooled to 0 ° C. 4 - ((6- (2- (2,4- Difluorophenyl) -1,1-difluor-2-oxoethyl) pyridin-3-yl) oxy) benzonitrile (4.00 g, 9.32 mmols) in THF ( 39 mL), was added slowly to keep the temperature below 5 ° C (internal probe temperature). The reaction was maintained at 0 ° C for 30 minutes (TLC indicated complete conversion to the product), and saturated sodium bicarbonate was added to temper the reaction. Brine was added, and the mixture was extracted with Et2O. The combined organic phases were diluted with hexanes and washed with brine (2x) and water (1x), dried (MgSO4) and concentrated to give the title compound as an amber oil (3,980 g, 96%): 1H NMR (300 MHz , CDCl3) δ 8.46 (d, J = 2.7 Hz, 1H), 7.73 - 7.62 (m, 2H), 7.52 (dd, J = 8.6, 0.6 Hz, 1H), 7.48 - 7.35 (m, 2H), 7.13 - 7.02 (m, 2H), 6.92 - 6.80 (m, 1H), 6.75 (ddd, J = 10.0, 8.9, 2.5 Hz, 1H), 3.46 (d, J = 5.1 Hz, 1H), 3.03 - 2.96 (m, 1H); ESIMS m / z 401 ([M + H] +). Example 2: Preparation of 4 - ((6- (3-azido-2- (2,4-difluorophenyl) -1,1-difluoro-2-hydroxypropyl) pyridin-3-yl) oxy) benzonitrile

[0024] Method A: A solution of 4 - ((6 - ((2- (2,4-difluorophenyl) oxiran-2-yl) difluoromethyl) pyridin-3-yl) oxy) benzonitrile (3.5 g, 8 , 74 mmols) and sodium azide (1.705 g, 26.2 mmols) in DMF (43.7 mL) was heated to 50 ° C for 17 hours. The reaction was poured into sat. aq. NaHCO3, and the mixture was extracted with Et2O (3x). The combined organic phases were washed with brine, dried (MgSO4) and concentrated to give the title compound as a brown oil (3.353 g, 69%): 1H NMR (300 MHz, CDCl3) δ 8.43 (m, 1H) , 7.67 (m, 3H), 7.57 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.7, 2.7 Hz, 1H), 7.09 ( m, 2H), 6.82 (m, 2H), 6.20 (s, 1H), 4.11 (m, 1H), 3.94 (dd, J = 12.9, 2.3 Hz, 1H ); ESIMS m / z 444 ([M + H] +).
[0025] Method B: A solution of 4 - ((6 - ((2- (2,4-difluorophenyl) oxiran-2-yl) difluoromethyl) pyridin-3-yl) oxy) benzonitrile (0.480 g, 1.199 mmol) , sodium azide (0.234 g, 3.60 mmol) and ammonium chloride (0.192 g, 3.60 mmol) in MeOH (6.00 mL) was heated to 50 ° C for 17 hours. The reaction was poured into sat. aq. NaHCO3 and the mixture was extracted with Et2O (3x). The combined organic phases were dried (MgSO4) and concentrated to give the title compounds as a yellow oil (410 mg, 62%). Example 3: Preparation of 1- (3- (5- (4-cyanophenoxy) pyridin-2-yl) -2- (2,4-difluorophenyl) -3,3-difluor-2-hydroxypropyl) -1H-tetrazole- 5- ethyl carboxylate

[0026] A mixture of 4 - ((6- (3-azido-2- (2,4-difluorophenyl) -1,1-difluoro-2-hydroxypropyl) pyridin-3-yl) oxy) benzonitrile (0.500 g, 0.902 mmol) and ethyl carbonocyanidate (0.134 mL, 1.353 mmol) was heated pure to 120 ° C in a screw cap flask for 16 hours. LCMS indicated complete conversion to the desired product. The 1H NMR analysis of the pure indicated 80% conversion to the product. The reaction mixture was diluted with DCM and purified by silica gel chromatography (0-100% EtOAc / hexanes) to give the title compound as a yellow oil (266 mg, 54%): 1H NMR (300 MHz, CDCl3 ) δ 8.23 (d, J = 2.7 Hz, 1H), 7.71 (m, 3H), 7.44 (m, 2H), 7.15 (m, 2H), 6.80 (m , 3H), 5.69 (d, J = 14.2 Hz, 1H), 5.57 (d, J = 14.4 Hz, 1H), 4.51 (q, J = 7.1 Hz, 2H ), 1.43 (t, J = 7.2 Hz, 3H); IR (thin film) 2228, 1740 cm-1; ESIMS m / z 444 ([M + H] +). Example 4. Preparation of 4 - ((6- (3- (5-acetyl-1H-tetrazol-1-yl) -2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxypropyl) pyridin- 3- il) oxy) benzonitrile

[0027] A mixture of 4 - ((6- (3-azido-2- (2,4-difluorophenyl) -1,1-difluoro-2-hydroxypropyl) pyridin-3-yl) oxy) benzonitrile (0.500 g, 0.902 mmol) and acetyl cyanide (0.096 mL, 1.353 mmol) was heated pure at 120 ° C in a screw cap flask for 16 hours. Pure 1H NMR indicated 44% conversion for the product. The reaction mixture was diluted with DCM and chromatographed (silica gel, 0-100% EtOAc / hexanes) to give the compound as a yellow oil (104 mg, 23%): 1H NMR (300 MHz, CDCl3) δ 8, 35 (d, J = 2.7 Hz, 1H), 7.70 (m, 3H), 7.48 (dd, J = 8.7, 2.7 Hz, 1H), 7.36 (td, J = 8.9, 6.5 Hz, 1H), 7.14 (m, 2H), 6.84 (m, 1H), 6.73 (m, 1H), 6.54 (s, 1H), 5 , 63 (d, J = 14.0 Hz, 1H), 5.56 (d, J = 14.9 Hz, 1H), 2.81 (s, 3H); IR (thin film) 2229, 1714 cm-1; ESIMS m / z 513 ([M + H] +). Example 5: Preparation of 4 - ((6- (3- (5-benzoyl-1H-tetrazol-1-yl) -2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxypropyl) pyridin- 3- il) oxy) benzonitrile

[0028] A mixture of 4 - ((6- (3-azido-2- (2,4-difluorophenyl) -1,1-difluoro-2-hydroxypropyl) pyridin-3-yl) oxy) benzonitrile (0.200 g, 0.361 mmol) and benzoyl kineto (0.064 mL, 0.541 mmol) were heated pure to 120 ° C in a screw cap flask for 16 hours. 1H NMR of the pure indicated 47% conversion to the product. The reaction mixture was diluted with DCM and purified by silica gel chromatography (0-50% EtOAc / hexanes) to give the title compound as a yellow oil (73 mg, 32%): 1H NMR (400 MHz, CDCl3 ) δ 8.27 (d, J = 2.7 Hz, 1H), 8.20 (dt, J = 8.5, 1.5 Hz, 2H), 7.72 (m, 3H), 7.66 (app d, J = 8.6 Hz, 1H), 7.56 (m, 2H), 7.46 (dd, J = 8.6, 2.7 Hz, 1H), 7.31 (td, J = 8.9, 6.5 Hz, 1H), 7.13 (m, 2H), 6.81 (ddd, J = 12.0, 8.5, 2.6 Hz, 1H), 6.71 ( m, 2H), 5.71 (d, J = 14.2 Hz, 1H), 5.60 (dd, J = 14.3, 1.0 Hz, 1H); IR (thin film) 2229, 1670 cm -1; ESIMS m / z 575 ([M + H] +). Example 6: Preparation of 4 - ((6- (2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxy-3- (5-tosyl-1H-tetrazol-1-yl) propyl) pyridin -3- yl) oxy) benzonitrile

[0029] A mixture of 4 - ((6- (3-azido-2- (2,4-difluorophenyl) -1,1-difluoro-2-hydroxypropyl) pyridin-3-yl) oxy) benzonitrile (1,700 g, 3.07 mmols) and 4-methylbenzenesulfonyl cyanide (0.834 g, 4.60 mmols) was heated pure at 100 ° C, in a flask for 16 hours. The reaction was cooled to room temperature, diluted with DCM and purified by silica gel chromatography (0-50% EtOAc / hexanes) to give the title compound as a pale yellow foam (1.109 g, 57%): 1H NMR (300 MHz, CDCl3) δ 8.37 (d, J = 2.7 Hz, 1H), 7.98 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.6 Hz, 1H), 7.68 (m, 2H), 7.51 (m, 2H), 7.42 (d, J = 8.5 Hz, 2H), 7.13 (m, 2H), 6, 83 (m, 2H), 6.67 (s, 1H), 5.70 (d, J = 13.7 Hz, 1H), 5.58 (d, J = 14.2 Hz, 1H), 2, 48 (s, 3H); IR (thin film) 3107, 2229, 1158 cm -1; ESIMS m / z 626 ([M + H] +). Example 7: Preparation of 4 - ((6- (2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxy-3- (1H-tetrazol-1-yl) propyl) pyridin-3-yl ) oxy) benzonitrile

[0030] Method A: By saponification / decarboxylation of ethyl ester and extraction. To a solution of 1- (3- (5- (4-cyanophenoxy) pyridin-2-yl) - 2- (2,4-difluorophenyl) -3,3-difluor-2-hydroxypropyl) -1H-tetrazole-5 2-ethyl carboxylate (0.097 g, 0.179 mmol) in EtOH (0.203 mL) and water (2.032 mL) at room temperature 2N sodium hydroxide (0.447 mL, 0.894 mmol) was added. The reaction was stirred at room temperature for 30 minutes. The reaction was then acidified with 1N HCl, resulting in an off-white precipitate formation. The mixture was extracted with EtOAc, and the combined organic phases were dried (MgSO4) and concentrated to give the title compound as a pale yellow oil (83 mg, 99%): 1H NMR (300 MHz, CDCl3) δ 8.74 (s, 1H), 8.26 (d, J = 2.7 Hz, 1H), 7.71 (m, 2H), 7.62 (d, J = 8.7 Hz, 1H), 7.43 (m, 2H), 7.19 (s, 1H), 7.12 (m, 2H), 6.76 (m, 2H), 5.44 (d, J = 14.4 Hz, 1H), 5 , 23 (dd, J = 14.4, 1.5 Hz, 1H); ESIMS m / z 469 ([M-H] -).
[0031] Method B: By saponification / decarboxylation of ethyl ester and filtration. To a solution of 1- (3- (5- (4-cyanophenoxy) pyridin-2-yl) - 2- (2,4-difluorophenyl) -3,3-difluor-2-hydroxypropyl) -1H-tetrazole-5 ethyl carboxylate (0.142 g, 0.262 mmol) in EtOH (0.238 mL) and water (2.380 mL) at room temperature, 2N sodium hydroxide (0.654 mL, 1.309 mmol) was added. The reaction was stirred at room temperature for 30 minutes. The reaction was acidified with 1N HCl, resulting in an off-white precipitate formation, which was isolated by filtration, washing with water. The solid was dried under vacuum for 2 hours to give the title compound as a white crystalline solid (106 mg, 86%).
[0032] Method C: By acylation with piperidine. To a solution of 4 - ((6- (3- (5-acetyl-1H-tetrazol-1-yl) -2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxypropyl) pyridin-3 -yl) oxy) benzonitrile (0.045 g, 0.088 mmol) in EtOH (0.220 mL) at room temperature, piperidine (8.69 μl, 0.088 mmol) was added. The reaction was stirred at room temperature overnight. The product had started to form after 18 hours, but some starting material remained. The reaction was heated to 40 ° C for 24 hours. LCMS indicated complete consumption of the starting material. 1N HCl was added, and the mixture was extracted with DCM. The combined organic phases were dried (MgSO4) and concentrated to give the title compound as a pale yellow oil (37 mg, 67%).
[0033] Method D: By acylation with sodium hydroxide. To a solution of 4 - ((6- (3- (5-acetyl-1H-tetrazol-1-yl) -2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxypropyl) pyridin-3 -yl) oxy) benzonitrile (0.045 g, 0.088 mmol) in EtOH (0.439 mL) at room temperature, 10% aqueous sodium hydroxide (0.070 mL, 0.176 mmol) was added. The reaction was stirred at room temperature for 1 hour, after which the TLC analysis indicated complete consumption of the starting material. 1N HCl was added, and an off-white precipitate was formed. The mixture was extracted with DCM, and the combined organic phases were dried (MgSO4) and concentrated to give the title compound as a pale yellow oil (33 mg, 76%).
[0034] Method E: By debenzoylation with sodium hydroxide. For a solution of 4 - ((6- (3- (5-benzoyl-1H-tetrazol-1-yl) -2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxypropyl) pyridin-3 -yl) oxy) benzonitrile (0.058 g, 0.091 mmol) in EtOH (0.454 mL) at room temperature 10% sodium hydroxide (0.073 mL, 0.182 mmol) was added. The reaction was stirred at room temperature for 30 minutes, after which TLC analysis indicated complete consumption of starting material. 1N HCl was added, and an off-white precipitate was formed. The mixture was extracted with DCM, and the combined organic phases were dried (MgSO4) and concentrated to give the compound as a pale yellow oil (39 mg, 91%).
[0035] Method F: By desulfonylation. To a solution of 4 - ((6- (2- (2,4-difluorophenyl) -1,1-difluor-2-hydroxy-3- (5-tosyl-1H-tetrazol-1-yl) propyl) pyridin- 3-yl) oxy) benzonitrile (0.100 g, 0.160 mmol) in acetic acid (3.20 mL) zinc powder was added (0.105 g, 1.601 mmol). The reaction was heated to 60 ° C for 5 hours, after which LCMS indicated 53% conversion to product. Additional zn was added, and the reaction was heated to 90 ° C for 3 hours. The reaction was filtered through a plug of celite washing with acetic acid. The mixture was concentrated to 1 ml, and water was added. The mixture was carefully neutralized with saturated aqueous NaHCO3, and the mixture was extracted with DCM. The combined organic phases were dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography (0-50% EtOAc / hexanes) to give the title compound as a colorless oil (33 mg, 44%). Biological Examples Example A: Fungicidal Activity Assessment: Wheat Leaf Spot (Mycosphaerella graminicola; Anamorph: Septoria tritici; Bayer SEPTTR code):
[0036] Technical levels of materials shown in Table 1 below were dissolved in acetone, which were then mixed with nine volumes of water containing 110 ppm Triton X-100. The fungicide solutions were applied to wheat seeds, using an automatic cabin atomizer to drain. All atomized plants were left to air dry before further handling. All fungicides were evaluated using the method mentioned above for their activities vs. all target diseases.
[0037] Wheat plants (variety Yuma) grew from seed in a greenhouse in 50% mineral soil / 50% less soil mix until the first leaf has fully emerged, with 710 seeds per pot. These plants were inoculated with an aqueous spore suspension of Septoria tritici, before or after fungicide treatments. After inoculation, the plants were kept at 100% relative humidity (one day in a dark dew chamber, followed by two to three days in a dew chamber lit at 20 ° C) to allow the spores to germinate and infect the leaf . The plants were then transferred to an established greenhouse at 20 ° C for the disease to develop. When the symptoms of the disease were fully expressed in the first leaves of untreated plants, the levels of infection were assessed on a scale of 0 to 100 percent severity of the disease. The percentage control of the disease was calculated using the disease severity rate in the treated plants in relation to the untreated plants. The results are shown below in Table 1. Example B: Evaluation of Fungicidal Activity .: Brown Rust from Wheat (Puccinia triticina; Synonym: Puccinia recondita f. Sp. Tritici; Bayer PUCCRT code):
[0038] Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil / 50% Measure minus soil mixture, until the first leaf has fully emerged, with 7-10 seeds per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticin, before or after fungicide treatments. After inoculation, the plants were kept in a dark dew room at 22 ° C with 100% relative humidity overnight, to allow the spores to germinate and infect the leaf. The plants were then transferred to a greenhouse placed at 24 ° C for the disease to develop. Fungicide formulation, application and disease evaluation followed the procedures as described in Example A. The results are shown below in Table 1.
[0039] In each case in Table 1, the rating scale for Septoria and Puccinia is as follows:
Table 1. Biological Data for Compounds of Formula (IV)

* SEPTTR - Wheat Leaf Stain (Septoria tritici) * PUCCRT - Wheat Leaf Rust (Puccinia recondita tritici) * 1DP - 1 Day of Protector * 3DC - 3 Days of Dressing * 1DC - 1 Day of Dressing

权利要求:
Claims (18)
[0001]
1. Method of preparing compounds, characterized by the fact that it presents Formula IV including the stage of:
[0002]
2. Method according to claim 1, characterized in that the step of contacting compounds of Formula III with R2-CN is carried out between 90 ° C and 130 ° C.
[0003]
3. Method according to claim 1, characterized by the fact that it also includes the step of counting a compound of Formula II with sodium azide and a solvent
[0004]
Method according to claim 3, characterized in that the solvent is selected from dimethylformamide and methanol.
[0005]
Method according to claim 3, characterized in that the step of contacting the compound of Formula II with sodium azide and a solvent is carried out between 40 ° C and 60 ° C.
[0006]
6. Method according to claim 3, characterized in that it also includes the step of contacting the compound of Formula I with trimethylsulfoxonium iodide and a base
[0007]
Method according to claim 6, characterized in that the base is sodium hydride.
[0008]
Method according to claim 1, characterized by the fact that R2 is -CO2Et, still comprising the steps of: contacting a compound of Formula IV with sodium hydroxide forming a mixture; and contacting the mixture with hydrochloric acid.
[0009]
9. Method according to claim 1, characterized by the fact that R2 is one of -C (O) Me and -C (O) Ph, further comprising the step of: contacting the compound of Formula IV with a base and a solvent.
[0010]
10. Method according to claim 9, characterized by the fact that the solvent is ethanol.
[0011]
11. Method according to claim 9, characterized in that the base is a sodium hydroxide and piperidine.
[0012]
12. Method according to claim 9, characterized in that the step of contacting the compound of Formula IV with the base and the solvent is carried out between 60 ° C and 90 ° C.
[0013]
13. Method according to claim 1, characterized in that R2 is -SO2 (4-MePh), further comprising the step of: contacting the compound of Formula IV with Zn and an acid.
[0014]
14. Method according to claim 13, characterized in that the acid is acetic acid.
[0015]
15. Compound, characterized by the fact that it presents Formula V,
[0016]
16. Method of using a Formula IV compound as defined in claim 1, characterized in that it is for the protection of a plant against attack by a phytopathogenic organism, or treatment, of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula IV, or a composition comprising the compound for a soil, a plant, a part of a plant, an area adjacent to the plant, foliage, roots and seeds.
[0017]
17. Method of preparing compounds of Formula VI, characterized by the fact that it comprises the step of:
[0018]
18. Method according to claim 17, characterized by the fact that the acid is acetic acid.

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同族专利:

公开号 | 公开日

EP3119753A4|2017-08-30|

US20170081316A1|2017-03-23|

WO2015143188A8|2016-09-29|

JP2017512780A|2017-05-25|

IL247833D0|2016-11-30|

EP3119753B1|2020-11-04|

IL247833A|2019-10-31|

CN106103424A|2016-11-09|

CA2942979A1|2015-09-24|

WO2015143188A1|2015-09-24|

US9914726B2|2018-03-13|

EP3119753A1|2017-01-25|

MX2016012058A|2017-01-19|

MX371291B|2020-01-24|

JP6613391B2|2019-12-04|

KR20160134672A|2016-11-23|

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