HERBICIDAL PYRIDYLETHERS

Abstract

The present invention relates to pyridylethers of formula (I) or their agriculturally acceptable salts or derivatives, wherein the variables are defined accord-ing to the description, processes and intermediates for preparing the pyridylethers of formula (I), compositions comprising them and their use as herbicides, i.e. for controlling harmful plants, and also a method for controlling unwanted vegetation which comprises allowing a herbicidal effective amount of at least one pyridylether of formula (I) to act on plants, their seed and/or their habitat.

##STR00001##

Claims

1. A pyridylether of formula (I) ##STR00131## wherein the variables have the following meanings: R.sup.1H or halogen; R.sup.2H, halogen, CN, NO.sub.2, NH.sub.2, CF.sub.3 or C(S)NH.sub.2; R.sup.3H, halogen, CN, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-haloalkyl, C.sub.1-C.sub.3-alkoxy, C.sub.1-C.sub.3-haloalkoxy, C.sub.1-C.sub.3-alkylthio, (C.sub.1-C.sub.3-alkyl)amino, di(C.sub.1-C.sub.3-alkyl)amino, C.sub.1-C.sub.3-alkoxy-C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxycarbonyl; R.sup.4H, halogen, C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy; R.sup.5 OR.sup.6, SR.sup.6, NR.sup.7R.sup.8, NR.sup.6OR.sup.6, NR.sup.6S(O).sub.2R.sup.7 or NR.sup.6S(O).sub.2NR.sup.7R.sup.8, wherein R.sup.6 is hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-alkenyl, C.sub.3-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.6-haloalkenyl, C.sub.3-C.sub.6-haloalkynyl, C.sub.1-C.sub.6-cyanoalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkoxy)C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkoxy-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-alkenyloxy-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-haloalkenyloxy-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-alkenyloxy-C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkylthio-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkylsulfinyl-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkylsulfonyl-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkylcarbonyl-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxycarbonyl-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkoxycarbonyl-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-alkenyloxycarbonyl-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-alkynyloxycarbonyl-C.sub.1-C.sub.6-alkyl, amino, (C.sub.1-C.sub.6-alkyl)amino, di(C.sub.1-C.sub.6-alkyl)amino, (C.sub.1-C.sub.6-alkylcarbonyl)amino, amino-C.sub.1-C.sub.6-alkyl, (C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkyl)amino-C.sub.1-C.sub.6-alkyl, aminocarbonyl-C.sub.1-C.sub.6-alkyl, (C.sub.1-C.sub.6-alkyl)aminocarbonyl-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkyl)aminocarbonyl-C.sub.1-C.sub.6-alkyl, NCR.sup.9R.sup.10, wherein R.sup.9 and R.sup.10 independently of one another are H, C.sub.1-C.sub.4-alkyl or phenyl; C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-heterocyclyl, C.sub.3-C.sub.6-heterocyclyl-C.sub.1-C.sub.6-alkyl, phenyl, phenyl-C.sub.1-C.sub.4-alkyl or a 5- or 6 membered heteroaryl, wherein each cycloalkyl, heterocyclyl, phenyl or heteroaryl ring can be substituted by one to four substituents selected from R.sup.13 or a 3- to 7-membered carbocyclus, which carbocyclus optionally has in addition to carbon atoms one or two ring members selected from the group consisting of N(R.sup.9), NN, C(O), O and S, and which carbocyclus is optionally substituted with one to four substituents selected from R.sup.11; wherein R.sup.11 is halogen, NO.sub.2, CN, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-alkoxycarbonyl; R.sup.7, R.sup.8 independently of one another are R.sup.6, or together form a 3- to 7-membered carbocyclus, which carbocyclus optionally has in addition to carbon atoms one or two ring members selected from the group consisting of N(R.sup.9), NN, C(O), O and S, and which carbocyclus is optionally substituted with one to four substituents selected from R.sup.11; n 1 to 3; Q O, S, SO, SO.sub.2, NH or (C.sub.1-C.sub.3-alkyl)N; W O or S; X O or S; Y is a heterocycle selected from the group consisting of Y.sup.1 to Y.sup.75 ##STR00132## ##STR00133## ##STR00134## ##STR00135## ##STR00136## ##STR00137## ##STR00138## ##STR00139## ##STR00140## ##STR00141## wherein A.sup.1, A.sup.2, A.sup.3 are oxygen or sulfur; A.sup.4 is oxygen, sulphur, SO or SO.sub.2; R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17 and R.sup.18 are hydrogen, hydroxy, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-cycloalkyloxy, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkenyloxy, C.sub.3-C.sub.6-alkynyl, C.sub.3-C.sub.6-alkynyloxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-alkylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl, C.sub.1-C.sub.6-alkoxysulfonyl, C.sub.1-C.sub.6-alkylsulfonyloxy, amino, C.sub.1-C.sub.6-alkylamino or di(C.sub.1-C.sub.6-alkyl)amino; or R.sup.12 and R.sup.13 together with the atoms to which they are attached, form a three- to six-membered cycle, which is saturated, partial unsaturated or aromatic, which may comprise apart from carbon atoms one to four nitrogen atoms, or one or two oxygen atoms, or one or two sulfur atoms, or one to three nitrogen atoms and an oxygen atom, or one to three nitrogen atoms and a sulfur atom, or one sulfur and one oxygen atom, and which for its part may be partially or fully halogenated and/or substituted by one to three radicals from the group consisting of C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-alkoxy; R.sup.19, R.sup.20, R.sup.21, R.sup.22, R.sup.23, R.sup.24 are hydrogen, cyano, hydroxy, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-cyanoalkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-cycloalkyloxy, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkenyloxy, C.sub.3-C.sub.6-alkynyl, C.sub.3-C.sub.6-alkynyloxy, C.sub.1-C.sub.6-alkylsulfinyl, C.sub.1-C.sub.6-alkylsulfonyl, phenyl-C.sub.1-C.sub.6-alkyl, amino, C.sub.1-C.sub.6-alkylamino or di(C.sub.1-C.sub.6-alkyl)amino; or R.sup.21 and R.sup.22 together with the atoms to which they are attached, form a three- to six-membered cycle, which is saturated, partial unsaturated or aromatic, which may comprise apart from carbon atoms one to four nitrogen atoms, or one or two oxygen atoms, or one or two sulfur atoms, or one to three nitrogen atoms and an oxygen atom, or one to three nitrogen atoms and a sulfur atom, or one sulfur and one oxygen atom, and which for its part may be partially or fully halogenated and/or substituted by one to three radicals from the group consisting of C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.6-alkoxy; R.sup.25 is hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.2-C.sub.6-alkenyl, C.sub.3-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkoxy, amino, C.sub.1-C.sub.6-alkylamino or di(C.sub.1-C.sub.6-alkyl)amino; R.sup.26 and R.sup.27 are hydrogen, halogen or C.sub.1-C.sub.6-alkyl; R.sup.28, R.sup.29 and R.sup.30 are hydrogen, halogen, hydroxy, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-cycloalkyloxy, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkenyloxy, C.sub.3-C.sub.6-alkynyl or C.sub.3-C.sub.6-alkynyloxy; and R.sup.31 is hydrogen, NH.sub.2, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-alkynyl; R.sup.32, R.sup.33 and R.sup.34 are hydrogen, amino, nitro, cyano, carboxy, carbamoyl, thiocarmbamoyl, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-cycloalkyloxy, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.1-C.sub.6-alkylthio, C.sub.1-C.sub.6-haloalkylthio, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-haloalkenyl, C.sub.2-C.sub.6-alkenyloxy, C.sub.3-C.sub.6-alkynyl, C.sub.3-C.sub.6-alkynyloxy, C.sub.1-C.sub.6-alkoxycarbonyl, C.sub.2-C.sub.6-alkenylthio, C.sub.3-C.sub.6-alkynylthio, C.sub.1-C.sub.6-alkylamino, di(C.sub.1-C.sub.6-alkyl)amino or C.sub.3-C.sub.7-cycloalkyl-C.sub.1-C.sub.3-alkyl; R.sup.35 and R.sup.36 are hydrogen, cyano, hydroxyl, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.3-C.sub.7-cycloalkyl, C.sub.3-C.sub.7-cycloalkyloxy, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.6-alkenyl, C.sub.3-C.sub.6-alkynyl, C.sub.1-C.sub.6-alkoxycarbonyl, amino, C.sub.1-C.sub.6-alkylamino, di(C.sub.1-C.sub.6-alkyl)amino, C.sub.3-C.sub.7-cycloalkyl-C.sub.1-C.sub.3-alkyl, phenyl or phenyl-C.sub.1-C.sub.6-alkyl; Z phenyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, each of which is optionally substituted by 1 to 4 substituents selected from the group consisting of halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy; including their agriculturally acceptable salts or derivatives, provided the compounds of formula (I) have a carboxyl group.

2. The pyridylether of formula (I) according to claim 1 wherein R.sup.1 is H or F, and R.sup.2 is F, C or CN.

3. The pyridylether of formula (I) according to claim 1, wherein R.sup.3 is H, C.sub.1-C.sub.3-alkyl or C.sub.1-C.sub.3-alkoxy, and R.sup.4 is H.

4. The pyridylether of formula (I) according to claim 1, wherein R.sup.5 is OR.sup.6 NR.sup.6S(O).sub.2R.sup.7 or NR.sup.6S(O).sub.2NR.sup.7R.sup.8, wherein R.sup.6 is hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.3-C.sub.6-alkenyl, C.sub.3-C.sub.6-alkynyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy-C.sub.1-C.sub.6-alkyl, di(C.sub.1-C.sub.6-alkoxy)C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkylcarbonyl-C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-alkoxycarbonyl-C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.6-alkyl; and R.sup.7, R.sup.8 are C.sub.1-C.sub.6-alkyl.

5. The pyridylether of formula (I) according to claim 1 wherein n is 1.

6. The pyridylether of formula (I) according to claim 1 wherein Q, W and X are O.

7. The pyridylether of formula (I) according to claim 1, wherein Y is selected from the group consisting of Y.sup.2, Y.sup.13, Y.sup.20, Y.sup.31, Y.sup.37, Y.sup.38, Y.sup.39, Y.sup.42, Y.sup.48, Y.sup.55, Y.sup.65, Y.sup.66, Y.sup.67 or Y.sup.68.

8. The pyridylether of formula (I) according to claim 1, wherein Z is phenyl or pyridyl, each of which is optionally substituted by 1 to 4 substituents selected from the group consisting of halogen, CN, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy and C.sub.1-C.sub.6-haloalkoxy.

9. A process for the preparation of a Pyridylether of formula (I) as defined in claim 1, wherein pyridines of formula (II) ##STR00142## wherein R.sup.1, R.sup.2 and Y are as defined in claim 1; and L.sup.1 is halogen, C.sub.1-C.sub.6-alkylsulfonate or arylsulfonate; are reacted with compounds of formula (III) ##STR00143## wherein R.sup.3, R.sup.4, R.sup.5, n, Q, W, X and Z are as defined in claim 1; in the presence of a base.

10. A process for the preparation of a pyridylether of formula (I), wherein Y is Y.sup.76, wherein A.sup.1 and A.sup.2 are O, R.sup.12 is CF.sub.3, R.sup.13 is H, R.sup.14 is OH and R.sup.22 is H, and R.sup.1, R.sup.2, R.sup.3, R.sup.4, R, Q, X, W, Z and n are as defined in claim 1 ##STR00144## wherein Y is Y.sup.76 with A.sup.1 and A.sup.2=O, R.sup.12CF.sub.3, R.sup.13 and R.sup.22H, R.sub.14OH wherein a compound of formula (XVII), ##STR00145## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, Q, X, W, Z and n are as defined in claim 1, is reacted with KOCN.

11. A compound of formula (XVIII) ##STR00146## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, Q, X, W, Z and n are as defined in claim 1.

12. A herbicidal composition comprising an herbicidally active amount of at least one pyridylether of formula (I) as claimed in claim 1 and at least one inert liquid and/or solid carrier and, optionally, at least one surface-active substance.

13. A process for the preparation of herbicidal active compositions, which comprises mixing an herbicidally active amount of at least one pyridylether of formula (I) as claimed in claim 1 and at least one inert liquid and/or solid carrier and, optionally, at least one surface-active substance.

14. A method of controlling undesired vegetation, which comprises allowing an herbicidally active amount of at least one pyridylether of formula (I) as claimed in claim 1 to act on plants, their environment or on seed.

15. A pyridylether of formula (I) as claimed in claim 1 for use as an herbicide.

Description

A PREPARATION EXAMPLES

Example 1

Ethyl 2-[2-[[3-chloro-6-[4-(difluoromethyl)-3-methyl-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-pyridyl]oxy]phenoxy]acetate

[0942] ##STR00077##

Example 1 Step 1: (5-chloro-3,6-difluoro-2-pyridyl)hydrazine

[0943] ##STR00078##

[0944] To a solution of 0.5 g (2.98 mmol) of 2,3,6-trifluoro-5-chloro pyridine (CAS 2879-42-7) in 7 mL EtOH was added 0.23 g (2.98 mmol) hydrazine monohydrate at room temperature. The mixture was stirred at 60 C. for 18 hours, cooled to room temperature and filtered. The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 0.39 g (2.18 mmol, 73%) of the desired compound 1 step 1.

[0945] 1H-NMR (CDCl.sub.3, ppm): 7.33 (dd, J=9.00 Hz, J=6.63 Hz, 1H); 6.05 (br.s, 1H); 3.84 (br.s., 2H).

[0946] [M+H]=180.0; Rt=0.548 min.

Example 1 step 2: (2E/Z)-2-[(5-chloro-3,6-difluoro-2-pyridyl)hydrazono]propanoic acid

[0947] ##STR00079##

[0948] To a solution of 0.58 g (3.23 mmol) of compound 1 step 1 in 13 mL EtOH was added 0.29 g (3.23 mmol) pyruvic acid dropwise. The mixture was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 0.63 g (2.53 mmol, 78%) of the desired compound 1 step 2.

[0949] [M+H]=249.9; Rt=0.833 min.

Example 1 step 3: 2-(5-chloro-3,6-difluoro-2-pyridyl)-5-methyl-4H-1,2,4-triazol-3-one

[0950] ##STR00080##

[0951] To a solution of 3.4 g (13.6 mmol) of compound 1 step 2 in 45 mL toluene was added 1.38 g (13.6 mmol) of triethylamine, followed by dropwise addition of 3.75 g (13.6 mmol) of diphenyl phosphoryl azide at room temperature. The mixture was refluxed for 3 hours, cooled to room temperature and stirred for another 18 hours. The mixture was washed with sat. aqueous Na.sub.2CO.sub.3. The aqueous layer was extracted with ethyl acetate. The combined organic layer was dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 1.9 g (7.72 mmol, 57%) of the desired compound 1 step 3.

[0952] [M+H]=247.0; Rt=0.737 min.

Example 1 step 4: 2-(5-chloro-3,6-difluoro-2-pyridyl)-4-(difluoromethyl)-5-methyl-1,2,4-triazol-3-one

[0953] ##STR00081##

[0954] To a solution of 28.0 g (113 mmol) of compound 1 step 3 in 455 mL acetonitrile was added 17.3 g (125 mmol) of potassium carbonate, followed by 27.7 g (136 mmol) of ethyl bromodifluoroacetate at room temperature. The mixture was refluxed for 6 hours, cooled to room temperature and stirred at room temperature for an additional 18 hours. The solvent was removed under reduced pressure, ethyl acetate was added and the mixture was washed with water. The organic layer was dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 3.24 g (10.95 mmol, 10%) of the desired compound 1 step 4.

[0955] 1H-NMR (CDCl.sub.3, ppm): 7.82 (dd, J=7.46 Hz, J=6.77 Hz, 1H); 7.04 (t, J=57.94 Hz, 1H); 2.50 (s, 3H).

[0956] [M+H]=297.0; Rt=1.005 min.

Example 1 Step 5: ethyl 2-[2-[[3-chloro-6-[4-(difluoromethyl)-3-methyl-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-pyridyl]oxy]phenoxy]acetate

[0957] ##STR00082##

[0958] To a solution of 2.8 g (9.47 mmol) of compound 1 step 4 in 38 mL tetrahydrofurane was added 3.09 g (9.47 mmol) of cesium carbonate, followed by 1.86 g (9.47 mmol) of ethyl 2-(2-hydroxyphenoxy)acetate (CAS 99186-63-7). The mixture was refluxed for 96 hours. The mixture was filtered and the solvent was removed under reduced pressure. The crude mixture was then dissolved in 50 mL EtOH, acidified to pH 3-4 by addition of conc. H.sub.2SO.sub.4 and stirred at room temperature for 18 hours. The solvent was removed under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The combined organic layer was washed with sat. aqueous NaCl, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 3.20 g (6.77 mmol, 71%) of the desired compound 1.

[0959] 1H-NMR (CDCl.sub.3, ppm): 7.75 (d, J=7.77 Hz, 1H); 7.23 (dd, J=7.91 Hz, J=1.63 Hz, 1H); 7.19 (ddd, J=8.17 Hz, J=7.57 Hz, J=1.67 Hz, 1H); 7.04 (dt, J=7.77 Hz, J=7.77 Hz, J=1.46 Hz, 1H); 6.95 (t, J=58.13 Hz, 1H); 6.93 (dd, J=8.18 Hz, J=1.44 Hz, 1H); 4.57 (s, 2H); 4.15 (q, J=7.14 Hz, 2H); 2.37 (s, 3H); 1.21 (t, J=7.14 Hz, 3H).

[0960] [M+H]=473.1; Rt=1.226 min.

Example 2: Ethyl 2-[2-[[3-carbamothioyl-5-fluoro-6-[4-methyl-5-oxo-3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-pyridyl]oxy]phenoxy]acetate

[0961] ##STR00083##

Example 2Step 1:2,5-difluoro-6-[4-methyl-5-oxo-3-(trifluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile

[0962] ##STR00084##

[0963] To a solution of 2.5 g (16.0 mmol) of 4-methyl-3-(trifluoromethyl)-1H-1,2,4-triazol-5-one (CAS 51856-10-1) in 40 mL dimethyl sulfoxide was added 2.4 g (16.0 mmol) of 2,5,6-trifluoropyridine-3-carbonitrile (CAS 870065-73-9) and 2.2 g (16.0 mmol) of potassium carbonate. The mixture was stirred for 16 hours at 20 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 3.1 g (9.6 mmol, 60%) of the desired compound 2 step 1.

[0964] 1H-NMR (CDCl.sub.3, ppm): 7.96-8.08 (m, 1H); 3.43-3.60 (m, 3H).

Example 2 Step 2: 5-fluoro-2-(2-methoxyphenoxy)-6-[4-methyl-5-oxo-3-(trifluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile

[0965] ##STR00085##

[0966] To a solution of 1.1 g (3.6 mmol) of compound 2 step 1 in 20 mL dimethyl sulfoxide was added 0.45 g (3.6 mmol) of 2-methoxyphenol (CAS 90-05-1) and 0.99 g (7.2 mmol) of potassium carbonate. The mixture was stirred for 16 hours at 50 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired compound 2 step 2 (2.5 g) which was used without further purification in the next step.

Example 2 Step 3: 5-fluoro-2-(2-hydroxyphenoxy)-6-[4-methyl-5-oxo-3-(trifluoromethyl)-1,2,4-triazol-1-yl]pyridine-3-carbonitrile

[0967] ##STR00086##

[0968] To a solution of 1.8 g (4.4 mmol) of compound 2 step 2 in 30 mL dichloromethane was added 3.3 g (13.2 mmol) of boron tribromide dropwise at 0 C. The mixture was stirred for 16 hours at 20 C. The mixture was poured into iced-water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 2 step 3 (1.9 g) which was used without further purification in the next step.

Example 2 Step 4: Ethyl 2-[2-[[3-cyano-5-fluoro-6-[4-methyl-5-oxo-3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-pyridyl]oxy]phenoxy]acetate

[0969] ##STR00087##

[0970] To a solution of 0.51 g (1.3 mmol) of compound 2 step 3 in 10 mL acetonitrile was added 0.26 g (1.6 mmol) of ethyl 2-bromoacetate (CAS 105-36-2) and 0.36 g (2.6 mmol) of potassium carbonate. The mixture was stirred for 16 hours at 20 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by reverse phase preparative HPLC (acetonitrile/water containing ammonium bicarbonate) to give 0.2 g (0.4 mmol, 32%) of the desired compound 2.

[0971] 1H-NMR (CDCl.sub.3, ppm): 7.95 (d, J=7.78 Hz, 1H); 7.21-7.26 (m, 2H); 7.04-7.10 (m, 1H); 6.94 (dd, J=8.16, 1.25 Hz, 1H); 4.59 (s, 2H); 4.09-4.18 (m, 2H); 3.39 (s, 3H).

[0972] [M+H]=481.9; Rt=1.189 min.

Example 3: Ethyl 2-[2-[[3-carbamothioyl-5-fluoro-6-[4-methyl-5-oxo-3-(trifluoromethyl)-1,2,4-triazol-1-yl]-2-pyridyl]oxy]phenoxy]acetate

[0973] ##STR00088##

[0974] Hydrogen sulfide was bubbled through a solution of 0.2 g (0.4 mmol) of compound 2 step 4 (compound 2) in 10 mL pyridine and 2 mL triethylamine at 15 C. The mixture was then stirred for 2 hours at 15 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was crystallized (from petrol ether/methyl tert-butyl ether 10:1) to give 0.4 g (0.37 mmol, 93%) of the desired compound 3.

[0975] 1H-NMR (CDCl.sub.3, ppm): 9.41 (br s, 1H); 8.73 (d, J=9.54 Hz, 1H); 8.17 (br s, 1H); 7.52 (dd, J=8.03, 1.51 Hz, 1H); 7.19-7.26 (m, 1H); 7.06-7.14 (m, 1H); 6.93 (d, J=8.16 Hz, 1H); 4.59 (s, 2H); 4.22 (q, J=7.15 Hz, 2H); 3.41 (s, 3H); 1.27 (t, J=7.15 Hz, 3H).

[0976] [M+H]=515.9; Rt=1.159 min.

Example 4

Ethyl 2-[2-[[3,5-dichloro-6-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-2-yl)-2-pyridyl]oxy]phenoxy]acetate

[0977] ##STR00089##

Example 4 Step 1: 2-(3,5,6-trichloro-2-pyridyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-3-one

[0978] ##STR00090##

[0979] To a solution of 8.5 g (61.1 mmol) of 5,6,7,8-tetrahydro-2H-[1,2,4]triazolo[4,3-a]pyridin-3-one (CAS 118801-67-5) in 5 mL DMF was added 13.15 g (61.1 mmol) of 2,3,5,6-tetrachloropyridine (CAS 2402-79-1) and 1.5 g (7.91 mmol) of potassium carbonate. The mixture was stirred for 17 hours at 20 C., and then for 17 hours at 100 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 3.5 g (9.78 mmol, 16%) of the desired compound 4 step 1.

[0980] 1H-NMR (CDCl.sub.3, ppm): 7.95-8.07 (m, 1H); 7.27 (d, J=2.51 Hz, 1H); 3.64-3.74 (m, 2H); 2.76-2.84 (m, 2H), 1.90-2.09 (m, 6H).

Example 4 Step 2: 2-[3,5-dichloro-6-(2-methoxyphenoxy)-2-pyridyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3-one

[0981] ##STR00091##

[0982] To a solution of 2.5 g (7.9 mmol) of compound 4 step 1 in 25 mL DMF was added 1 g (7.9 mmol) of 2-methoxyphenol (CAS 90-05-1) and 1.65 g (11.9 mmol) of potassium carbonate. The mixture was stirred for 17 hours at 100 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 3.2 g (7.9 mmol, 99%) of the desired compound 4 step 2.

[0983] 1H-NMR (CDCl.sub.3, ppm): 7.90 (s, 1H); 7.15-7.21 (m, 2H); 6.85-6.99 (m, 3H); 3.76 (s, 3H); 3.61 (t, J=6.06 Hz, 2H); 2.68 (t, J=6.39 Hz, 2H); 1.79-1.97 (m, 5H).

Example 4 Step 3: 2-[3,5-dichloro-6-(2-hydroxyphenoxy)-2-pyridyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3-one

[0984] ##STR00092##

[0985] To a solution of 3.2 g (7.88 mmol) of compound 4 step 2 in 35 mL dichloromethane was added 6.0 g (23.6 mmol) of boron tribromide dropwise at 0 C. The mixture was stirred for 17 hours at 20 C. The mixture was poured into iced-water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 4 step 3 (2.5 g) which was used without further purification in the next step.

[0986] 1H-NMR (CDCl.sub.3, ppm): 7.92 (s, 1H); 7.22 (d, J=7.50 Hz, 1H); 7.10-7.17 (m, 2H); 6.95-7.01 (m, 1H); 6.78-6.89 (m, 3H); 3.66 (t, J=6.06 Hz, 2H); 2.73 (t, J=6.39 Hz, 2H); 1.83-2.01 (m, 4H).

Example 4 Step 4: Ethyl 2-[2-[[3,5-dichloro-6-(3-oxo-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridin-2-yl)-2-pyridyl]oxy]phenoxy]acetate

[0987] ##STR00093##

[0988] To a solution of 1.0 g (2.5 mmol) of compound 4 step 3 in 10 mL acetonitrile was added 0.852 g (5.1 mmol) of ethyl 2-bromoacetate (CAS 105-36-2) and 0.704 g (5.1 mmol) of potassium carbonate. The mixture was stirred for 17 hours at 20 C. The solvent was removed under reduced pressure. The crude product was purified by reverse phase preparative HPLC (acetonitrile/water containing trifluoroacetic acid) to give 0.35 g (0.4 mmol, 16%) of the desired compound 4.

[0989] 1H-NMR (CDCl.sub.3, ppm): 7.92 (s, 1H); 7.24 (dd, J=7.91, 1.51 Hz, 1H); 7.17 (td, J=7.87, 1.57 Hz, 1H); 7.01-7.06 (m, 1H); 6.92-6.96 (m, 1H); 4.59 (s, 2H); 4.18 (q, J=7.15 Hz, 2H); 3.61 (t, J=6.02 Hz, 2H); 2.68 (t, J=6.40 Hz, 2H); 1.89-1.97 (m, 2H); 1.82-1.89 (m, 2H); 1.23 (t, J=7.15 Hz, 3H).

[0990] [M+H]=478.9; Rt=1.157 min.

Example 5: Ethyl 2-[2-[[6-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3-yl)-3,5-dichloro-2-pyridyl]oxy]phenoxy]acetate

[0991] ##STR00094##

Example 5 Step 1: 5-tert-butyl-3-[3,5-dichloro-6-(2-methoxyphenoxy)-2-pyridyl]-1,3,4-oxadiazol-2-one

[0992] ##STR00095##

[0993] To a solution of 4.5 g (14.0 mmol) of 5-tert-butyl-3-(3,5-dichloro-6-fluoro-2-pyridyl)-1,3,4-oxadiazol-2-one (CAS 68617-97-0) in 50 mL DMF was added 1.7 g (14.0 mmol) of 2-methoxyphenol (CAS 90-05-1) and 5.8 g (42.0 mmol) of potassium carbonate. The mixture was stirred for 17 hours at 80 C. The mixture was diluted with water and extracted with methyl tertbutyl ether. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 2.4 g (5.88 mmol, 42%) of the desired compound 5 step 1.

[0994] 1H-NMR (CDCl.sub.3, ppm): 7.92 (s, 1H); 7.18-7.26 (m, 2H); 6.96-7.01 (m, 2H); 3.77 (s, 3H); 1.30 (s, 9H).

Example 5 step 2: 5-tert-butyl-3-[3,5-dichloro-6-(2-hydroxyphenoxy)-2-pyridyl]-1,3,4-oxadiazol-2-one

[0995] ##STR00096##

[0996] To a solution of 2.4 g (5.8 mmol) of compound 5 step 1 in 30 mL dichloromethane was added 2.2 g (8.8 mmol) of boron tribromide dropwise at 0 C. The mixture was stirred for 17 hours at 20 C. The mixture was poured into iced-water and extracted with dichloromethane. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 5 step 2 (2.0 g) which was used without further purification in the next step.

[0997] 1H-NMR (CDCl.sub.3, ppm): 7.96-8.01 (m, 1H); 7.62-7.70 (m, 2H); 7.09-7.20 (m, 3H); 6.96-7.07 (m, 2H); 6.86-6.93 (m, 1H); 5.31 (s, 2H); 1.08 (s, 9H).

Example 5 step 3: Ethyl 2-[2-[[6-(5-tert-butyl-2-oxo-1,3,4-oxadiazol-3-yl)-3,5-dichloro-2-pyridyl]oxy]phenoxy]acetate

[0998] ##STR00097##

[0999] To a solution of 2.0 (5.0 mmol) compound step in 20 m acetonitrile was added 1.69 g (10.0 mmol) of ethyl 2-bromoacetate (CAS 105-36-2) and 2.79 g (20.0 mmol) of potassium carbonate. The mixture was stirred for 17 hours at 20 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 0.3 g (0.6 mmol, 12%) of the desired compound 5.

[1000] 1H-NMR (CDCl.sub.3, ppm): 7.96-8.01 (m, 1H); 7.62-7.70 (m, 2H); 7.09-7.20 (m, 3H); 6.96-7.07 (m, 2H); 6.86-6.93 (m, 1H); 5.31 (s, 2H); 1.08 (s, 9H).

[1001] [M+H]=482.0; Rt=1.387 min.

Example 6: Ethyl 2-[2-[[3-chloro-6-[4-chloro-5-(difluoromethoxy)-1-methyl-pyrazol-3-yl]-5-fluoro-2-pyridyl]oxy]phenoxy]acetate

[1002] ##STR00098##

Example 6 Step 1: 4-chloro-5-(difluoromethoxy)-3-iodo-1-methyl-pyrazole

[1003] ##STR00099##

[1004] To a solution of 5.2 g (20.56 mmol) of iodine in 25 mL acetonitrile was added 2.12 g (20.56 mmol) of tert-butyl nitrite at 0 C. under argon atmosphere. The mixture was stirred for 1 hour at 0 C. and then 2.7 g of 4-chloro-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-amine (CAS 149978-51-8) was added at 0 C. The mixture was stirred for 2 hours at 20 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with aq. Na.sub.2S.sub.2O.sub.3, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 3.2 g (15.6 mmol, 76%) of the desired compound 6 step 1.

Example 6Step 2:tributyl-[4-chloro-5-(difluoromethoxy)-1-methyl-pyrazol-3-yl]stannane

[1005] ##STR00100##

[1006] To a solution of 2.2 g (7.15 mmol) of compound 6 step 1 in 40 mL tetrahydrofuran was added 4.3 mL (8.6 mmol, 2M in THF) of iso-propyl magnesium chloride at 10 C. under argon atmosphere. The mixture was stirred for 15 minutes at 10 C. and then 2.8 g of tributyltin chloride (CAS 1461-22-9) was added slowly at 10 C. The mixture was stirred for 1.5 hours at 20 C. The mixture was quenched with a sat. aq. NH.sub.4Cl solution water and extracted with ethyl acetate.

[1007] The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 2.5 g (5.4 mmol, 75%) of the desired compound 6 step 2.

[1008] 1H-NMR (CDCl.sub.3, ppm): 6.82 (d, J=1.10 Hz, 1H); 6.63 (d, J=1.32 Hz, 1H); 6.45 (d, J=1.32 Hz, 1H); 3.77 (s, 3H); 1.48-1.65 (m, 6H); 1.10-1.39 (m, 17H); 0.80-0.96 (m, 16H).

Example 6 Step 3: 2-bromo-5-chloro-3-fluoro-6-(2-methoxyphenoxy)pyridine

[1009] ##STR00101##

[1010] To a solution of 7.7 g (107.8 mmol) of sodium azide in 120 mL dimethyl sulfoxide at 0 C. was added 18.0 g (118.6 mmol) of 3-chloro-2,5,6-trifluoropyridine (CAS 2879-42-7). The mixture was stirred 3 hours at 20 C. Then a solution of 14.0 g (113.0 mmol) of 2-methoxyphenol (CAS 90-05-1) was added to the above mixture at 0 C. in portions. The resulting mixture was stirred at 25 C. for 16 hours, diluted with ice water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 6 step 3 which was used without further purification in the next step.

Example 6 Step 4: 5-chloro-3-fluoro-6-(2-methoxyphenoxy)pyridin-2-amine

[1011] ##STR00102##

[1012] To a suspension of 18.0 g (61.1 mmol) of compound 6 step 3 and 35.0 g (537.0 mmol) zinc in 400 mL tetrahydrofuran was added dropwise 350 mL of a semi-saturated aqueous NH.sub.4Cl solution at 0 C. The mixture was stirred for 3 hours at 20 C., filtered and the filter cake was washed with ethyl acetate. To the filtrate was added water, the mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 16.0 g (59.5 mmol, 97%) of the desired product 6 step 4.

Example 6 Step 5: 2-bromo-5-chloro-3-fluoro-6-(2-methoxyphenoxy)pyridine

[1013] ##STR00103##

[1014] To a solution of 7.0 g (26.1 mmol of compound 6 step 4 in 70 mL acetonitrile was added 5.8 g (26.1 mmol) of copper(II) bromide and 3.0 g (28.7 mmol) of tert-butyl nitrite dropwise at 15 C. The mixture was stirred for 2 hours at 20 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 8.4 g (11.0 mmol, 42%) of the desired compound 6 step 5.

[1015] 1H-NMR (CDCl.sub.3, ppm): 7.57 (d, J=6.39 Hz, 1H); 7.21-7.26 (m, 1H); 7.12-7.17 (m, 1H); 6.97-7.04 (m, 2H); 3.76 (s, 3H).

Example 6 Step 6: 2-[(6-bromo-3-chloro-5-fluoro-2-pyridyl)oxy]phenol

[1016] ##STR00104##

[1017] To a solution of 6.4 g (19.2 mmol) of compound 6 step 5 in 20 mL dichloromethane was added 7.2 g (28.8 mmol) of boron tribromide dropwise at 0 C. The mixture was stirred for 1.5 hours at 20 C. The mixture was poured into iced-water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 6 step 6 (5.3 g) which was used without further purification in the next step.

[1018] 1H-NMR (CDCl.sub.3, ppm): 7.62 (d, J=6.17 Hz, 1H); 7.13-7.21 (m, 2H); 7.05-7.10 (m, 1H); 6.86-7.01 (m, 1H); 5.82 (br s, 1H); 4.13 (q, J=7.06 Hz, 1H); 2.05 (s, 2H); 1.27 (t, J=7.06 Hz, 2H).

Example 6 Step 7: ethyl 2-[2-[(6-bromo-3-chloro-5-fluoro-2-pyridyl)oxy]phenoxy]acetate

[1019] ##STR00105##

[1020] To a solution of 2.0 g (6.2 mmol) of compound 6 step 6 in 20 mL acetonitrile was added 1.7 g (12.2 mmol) of potassium carbonate and 2.1 g (12.6 mmol) of ethyl 2-bromoacetate (CAS 105-36-2) dropwise. The mixture was stirred for 17 hours at 20 C. The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 2.0 g (4.96 mmol, 80%) of the desired compound 6 step 7.

[1021] 1H-NMR (MeOD, ppm): 7.91 (d, J=6.78 Hz, 1H); 7.14-7.27 (m, 2H); 7.04-7.09 (m, 2H); 4.58 (s, 2H); 4.15 (q, J=7.07 Hz, 2H); 1.22 (t, J=7.09 Hz, 3H).

Example 6 Step 8: Ethyl 2-[2-[[3-chloro-6-[4-chloro-5-(difluoromethoxy)-1-methyl-pyrazol-3-yl]-5-fluoro-2-pyridyl]oxy]phenoxy]acetate

[1022] ##STR00106##

[1023] To a solution of 0.6 g (1.3 mmol) of compound 6 step 7 in 5 mL dry dimethylformamide was added 0.05 g (0.07 mmol) of bis(triphenylphosphine)palladium(II) dichloride and 0.5 g (1.3 mmol) of compound 5.2 under argon atmosphere. The mixture was stirred for 3 hours at 80 C.

[1024] The mixture was diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by reverse phase preparative HPLC (acetonitrile/water containing trifluoroacetic acid) to give 0.2 g (0.35 mmol, 27%) of the desired compound 6.

[1025] 1H-NMR (CDCl.sub.3, ppm): 7.67 (d, J=8.78 Hz, 1H); 7.24 (br d, J=7.91 Hz, 1H); 7.17 (br t, J=7.59 Hz, 1H); 7.01-7.08 (m, 1H); 6.93 (br d, J=8.16 Hz, 1H); 6.78 (s, 1H); 6.60 (s, 1H); 6.42 (s, 1H); 4.53 (s, 2H); 4.16 (q, J=6.99 Hz, 2H); 3.79 (s, 3H); 1.21 (t, J=7.09 Hz, 3H).

[1026] [M+H]=506.9; Rt=1.301 min.

Example 7: Ethyl 2-[[3-[[3-chloro-6-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazinan-1-yl)-5-fluoro-2-pyridyl]oxy]-2-pyridyl]oxy]acetate

[1027] ##STR00107##

Example 7 Step 1: Ethyl 2-[[3-[(6-azido-3-chloro-5-fluoro-2-pyridyl)oxy]-2-pyridyl]oxy]acetate

[1028] ##STR00108##

[1029] To a solution of 1.8 g (10.78 mmol) 3-chloro-2,5,6-trifluoropyridine (CAS 2879-42-7) in 20 mL dimethyl sulfoxide at 23 C. was added 0.77 g (11.8 mmol) of sodium azide. The mixture was stirred 3 hours at 23 C. Then a suspension of 2.2 g (11.3 mmol) ethyl 2-[(3-hydroxy-2-pyridyl)oxy]acetate (CAS: 353292-81-6) and 7.0 g (21.5 mmol) of cesium carbonate in 10 mL dimethyl sulfoxide was added to the above mixture in portions. The resulting mixture was stirred at 23 C. for 15 hours, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 7 step 1 which was used without further purification in the next step.

[1030] [M+H]=367.9; Rt=1.276 min.

Example 7 Step 2: Ethyl 2-[[3-[(6-amino-3-chloro-5-fluoro-2-pyridyl)oxy]-2-pyridyl]oxy]acetate

[1031] ##STR00109##

[1032] To a suspension of 4.8 g (13.0 mmol) of compound 7 step 1 and 4.3 g (66.0 mmol) zinc in 100 mL tetrahydrofuran was added dropwise 50 mL of a semi-saturated aqueous NH.sub.4Cl solution at 0 C. The mixture was stirred at 23 C. for 5 hours, filtered and the filter cake was washed with ethyl acetate. To the filtrate was added 200 mL water, the mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 2.7 g (8.0 mmol, 61%) of the desired product 7 step 2.

[1033] 1H-NMR (CDCl.sub.3, ppm): 7.9 (dd, J=4.89 Hz, J=1.51 Hz, 1H); 7.4 (d, J=7.39 Hz, 1H); 7.3 (d, J=9.06 Hz, 1H); 6.9 (dd, J=7.65 Hz, J=4.89 Hz, 1H); 4.9 (s, 2H); 4.5 (s, 2H); 4.2 (q, J=7.15 Hz, 2H); 1.25 (t, J=7.15 Hz, 3H).

[1034] [M+H]=428.1; Rt=1.332 min.

Example 7 Step 3: Ethyl 2-[[3-[[3-chloro-6-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazinan-1-yl)-5-fluoro-2-pyridyl]oxy]-2-pyridyl]oxy]acetate

[1035] ##STR00110##

[1036] To a solution of 1.0 g (3.1 mmol) of compound 7 step 2 in 10 mL ethyl acetate was added 1.5 g (9.2 mmol) of carbonyldiimidazole and 0.9 g (9.6 mmol) of triethyl amine. The mixture was stirred for 2 hours at 65 C. before 0.27 g (3.1 mmol) of N,N-dimethyl urea was added. The mixture was stirred for another 17 hours at 65 C. The mixture was diluted with ice-water, pH was adjusted to 7 with 6N HCl and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 0.25 g (0.5 mmol, 17%) of the desired compound 7.

[1037] 1H-NMR (CDCl.sub.3, ppm): 7.97 (dd, J=5.02, 1.51 Hz, 1H); 7.77 (d, J=7.15 Hz, 1H); 7.49 (dd, J=7.65, 1.63 Hz, 1H); 6.96 (dd, J=7.72, 4.96 Hz, 1H); 4.78 (s, 2H); 4.19 (q, J=7.15 Hz, 2H), 3.34 (s, 6H); 1.25 (t, J=7.09 Hz, 3H).

[1038] [M+H]=482.0; Rt=1.137 min.

Example 8: Ethyl 2-[[3-[[3-chloro-5-fluoro-6-[5-methyl-6-oxo-4-(trifluoromethyl)pyridazin-1-yl]-2-pyridyl]oxy]-2-pyridyl]oxy]acetate

[1039] ##STR00111##

[1040] To a solution of 2.0 g (6.1 mmol) of 2-(5-chloro-3,6-difluoro-2-pyridyl)-4-methyl-5-(trifluoromethyl)pyridazin-3-one (CAS 1114184-80-3) in 20 mL acetonitrile was added 1.3 g (6.5 mmol) of ethyl 2-[(3-hydroxy-2-pyridyl)oxy]acetate (CAS: 353292-81-6) and 4.0 g (12.3 mmol) of cesium carbonate. The mixture was stirred for 17 hours at 20 C. The solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (petrol ether/ethyl acetate) to give 0.3 g (0.6 mmol, 10%) of the desired compound 8.

[1041] 1H-NMR (CDCl.sub.3, ppm): 7.97 (dd, J=4.96, 1.65 Hz, 1H); 7.91 (s, 1H); 7.78 (d, J=7.50 Hz, 1H); 7.51 (dd, J=7.72, 1.54 Hz, 1H); 6.96 (dd, J=7.72, 4.85 Hz, 1H); 4.81 (s, 2H); 4.17 (q, J=7.06 Hz, 2H); 2.35-2.38 (m, 3H); 1.23 (t, J=7.06 Hz, 3H).

[1042] [M+H]=503.0; Rt=1.284 min.

[1043] The compounds listed below in tables 1 to 9 can be prepared similarly to the example mentioned above:

##STR00112## [1044] wherein R.sup.3 and R.sup.4 are H, R.sup.5 is OR with R.sup.6 is C.sub.2H, n is 1, Q, W and X are O, Y is Y.sup.20, wherein A.sup.1 is O, R.sup.21 is CF.sub.2H, R.sup.22 is CH.sub.3 and Z is Z-1 with R.sup.a, R.sup.b, R.sup.c and R.sup.d being H

TABLE-US-00005 TABLE 1 Example no R.sup.1 R.sup.2 m/z [M + H] R.sub.t [min] 9 F F 457 1.132 10 Cl Cl 489 1.218 11 H Cl 455 1.200 12 F CN 464 1.142

##STR00113## [1045] wherein R.sup.3 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, Y is Y.sup.20, wherein A.sup.1 is O, R.sup.21 is CF.sub.2H, R.sup.22 is CH.sub.3 and Z is Z-7 with R.sup.a, R.sup.b and R.sup.c being H

TABLE-US-00006 TABLE 2 Example no R.sup.1 R.sup.2 m/z [M + H] R.sub.t [min] 13 F Cl 474 1.175 14 F F 458 1.063 15 Cl Cl 490 1.187 16 H Cl 456 1.173 17 F CN 465 1.108

##STR00114## [1046] wherein R.sup.1 is F, R.sup.3 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, Y is Y.sup.20, wherein R.sup.21 is CH.sub.3 and R.sup.22 is CF.sub.3, and Z is Z-1 with R.sup.a, R.sup.b, R.sup.c and R.sup.d being H

TABLE-US-00007 TABLE 3 Example no R.sup.2 A.sup.1 m/z [M + H] R.sub.t [min] 18 CN S 497.9 1.262

##STR00115## [1047] wherein R.sup.1 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, is Y.sup.2, wherein R.sup.23 is CF.sub.2H, R.sup.24 is CH.sub.3, R.sup.28 is Cl, and Z is Z-7 with R.sup.a, R.sup.b and R.sup.c being H

TABLE-US-00008 TABLE 4 Example no R.sup.1 R.sup.2 m/z [M + H] R.sub.t [min] 19 F Cl 505.9 1.327

##STR00116## [1048] wherein R.sup.3 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, Y is Y.sup.67, wherein A.sup.1 and A.sup.2 are O, A.sup.3 is S, R.sup.35 and R.sup.36 are CH.sub.3, and Z is Z-7 with R.sup.a, R.sup.b and R.sup.c being H

TABLE-US-00009 TABLE 5 Exmaple no R.sup.1 R.sup.2 m/z [M + H] R.sub.t [min] 20 F Cl 497.9 1.276

##STR00117## [1049] wherein R.sup.3 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, Y is Y.sup.55, wherein A.sup.1 is O, R.sup.17 is CF.sub.3, R.sup.18 is CH.sub.3, R.sup.28 is H, and Z is Z-1 with R.sup.a, R.sup.b, R.sup.c and R.sup.d being H

TABLE-US-00010 TABLE 6 Example no R.sup.1 R.sup.2 m/z [M + H] R.sub.t [min] 21 F Cl 501.9 1.312

##STR00118## [1050] wherein R.sup.3 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, Y is Y.sup.66 wherein A.sup.1 is O, R.sup.12 is CF.sub.3, R.sup.13 is H, R.sup.35 is CH.sub.3, and Z is Z-1 with R.sup.a, R.sup.b, R.sup.c and R.sup.d being H

TABLE-US-00011 TABLE 7 Example no R.sup.1 R.sup.2 m/z [M + H] Rt [min] 22 F Cl 534.4 1.372 23 H Cl 516.1 1.270

##STR00119## [1051] wherein R.sup.3 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, Y is Y.sup.65, wherein A.sup.1 is O, R.sup.12 is H, R.sup.13 is CF.sub.3, R.sup.35 is CH.sub.3, and Z is Z-1 with R.sup.a, R.sup.b, R.sup.c and R.sup.d being H

TABLE-US-00012 TABLE 8 Example no R.sup.1 R.sup.2 m/z [M + H] Rt [min] 24 F Cl 501.9 1.197

##STR00120## [1052] wherein R.sup.3 and R.sup.4 are H, R.sup.5 is OR.sup.6 with R.sup.6 is C.sub.2H.sub.5, n is 1, Q, W and X are O, Y is Y.sup.65, wherein A.sup.1 is O, R.sup.12 is H, R.sup.13 is CF.sub.3, R.sup.35 is CH.sub.3, and Z is Z-7 with R.sup.a, R.sup.b and R.sup.c being H

TABLE-US-00013 TABLE 9 Example no R.sup.1 R.sup.2 m/z [M + H] Rt [min] 25 F Cl 502.9 1.167

Example 26: Ethyl 2-[2-[[3-chloro-5-fluoro-6-(5-isopropylidene-2,4-dioxo-oxazoidin-3-yl)-2-pyridyl]oxy]phenoxy]acetate

[1053] ##STR00121##

Example 26 step 1: ethyl 2-[2-[(6-amino-3-chloro-5-fluoro-2-pyridyl)oxy]phenoxy]acetate

[1054] ##STR00122##

[1055] To a solution of 40 g (0.24 mol) 3-chloro-2,5,6-trifluoropyridine (CAS 2879-42-7) in 400 mL dimethyl sulfoxide at 23 C. was added 17 g (0.26 mol) of sodium azide. The mixture was stirred 16 hours at 23 C. Then a suspension of 49 g (0.25 mol) ethyl 2-(2-hydroxyphenoxy)acetate (CAS: 99186-63-7) and 155 g (0.48 mol) of cesium carbonate in 100 mL dimethyl sulfoxide was added to the above mixture in portions. The resulting mixture was stirred at 23 C. for 15 hours, diluted with water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 26 step 1 which was used without further purification in the next step.

[1056] [M+H]=367.0; Rt=1.276 min.

Example 26 step 2: ethyl 2-[2-[(6-amino-3-chloro-5-fluoro-2-pyridyl)oxy]phenoxy]acetate

[1057] ##STR00123##

[1058] To a suspension of 34 g (93.0 mmol) of compound 26 step 1 and 15.1 g (232.0 mmol) zinc in 190 mL tetrahydrofuran was added dropwise 150 mL of a semi-saturated aqueous NH.sub.4Cl solution at 0 C. The mixture was stirred at 23 C. for 15 hours, filtered and the filter cake was washed with ethyl acetate. To the filtrate was added 200 mL water, the mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 26 step 2 which was used without further purification in the next step.

[1059] 1H-NMR (CDCl.sub.3, ppm): 7.34 (d, J=9.0 Hz, 1H), 7.18-7.09 (m, 2H), 7.06-6.99 (m, 1H), 6.95 (dd, J=8.1, 1.5 Hz, 1H), 4.57 (s, 2H), 4.20 (q, J=7.1 Hz, 2H), 3.97 (br, 2H), 1.25 (t, J=7.1 Hz, 3H).

[1060] [M+H]=341.1; Rt=1.123 min.

Example 26 Step 3: Ethyl 2-[2-[[3-chloro-5-fluoro-6-(5-isopropylidene-2,4-dioxo-oxazolidin-3-yl)-2-pyridyl]oxy]phenoxy]acetate

[1061] ##STR00124##

[1062] To a solution of 250 mg (0.73 mmol) of compound 26 step 2 in 8 mL acetonitrile were added 238 mg (1.47 mmol) 1,1-carbonyldiimidazole and 107 L (0.77 mmol) triethylamine. The mixture was stirred at 65 C. for 1 hour before 106 mg (0.73 mmol) of ethyl 2-hydroxy-3-methylbut-3-enoate was added. The mixture was stirred for another 17 hours at 80 C. The volatiles were removed under reduced pressure. The crude product was purified by column chromatography on silica (cyclohexane/ethyl acetate) to give 97 mg (0.21 mmol, 28%) of the desired product 26.

[1063] 1H-NMR (CDCl.sub.3, ppm): 7.77 (d, J=7.3 Hz, 1H), 7.23-7.15 (m, 2H), 7.03 (td, J=7.8, 1.5 Hz, 1H), 6.88 (dd, J=8.1, 1.5 Hz, 1H), 4.53 (s, 2H), 4.16 (q, J=7.1 Hz, 2H), 2.21 (s, 3H), 1.98 (s, 3H), 1.22 (t, J=7.1 Hz, 3H).

[1064] [M+H]=464.9; Rt=1.288.

Example 27: ethyl 2-[2-[[3-chloro-6-(1,3-dioxo-4,5,6,7-tetrahydroisoindol-2-yl)-5-fluoro-2-pyridyl]oxy]phenoxy]acetate

[1065] ##STR00125##

Example 27 Step 1: 2-[5-chloro-3-fluoro-6-(2-methoxyphenoxy)-2-pyridyl]-4,5,6,7-tetrahydroisoindole-1,3-dione

[1066] ##STR00126##

[1067] To a solution of 1.0 g (3.7 mmol) of compound 6 step 4 in 30 mL toluene was added 850 mg (5.6 mmol) of 3,4,5,6-tetrahydrophthalic anhydride (CAS 2426-02-0) and 1.0 g (5.6 mmol) of p-toluenesulfonic acid monohydrate (CAS 6192-52-5). The mixture was stirred for 16 hours at 100 C. The reaction mixture was filtered and the solvent was removed under reduced pressure.

[1068] The crude product was purified by column chromatography on silica (cyclohexane/ethyl acetate) to give 715 mg (1.7 mmol, 48%) of the desired product 27 step 1.

[1069] [M+H]=403.0; Rt=1.284.

Example 27 Step 2: 2-[5-chloro-3-fluoro-6-(2-hydroxyphenoxy)-2-pyridyl]-4,5,6,7-tetrahydroisoindole-1,3-dione

[1070] ##STR00127##

[1071] To a solution of 660 mg (1.6 mmol) of compound 27 step 1 in 12 mL dichloromethane was added 820 mg (3.3 mmol) of boron tribromide dropwise at 60 C. The mixture was stirred for 15 hours at 20 C. The mixture was poured into iced-water and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous MgSO.sub.4, filtered and the solvent was removed under reduced pressure to give the desired product 27 step 2 (630 mg) which was used without further purification in the next step.

[1072] [M+H]=389.0; Rt=1.165.

Example 27 Step 3: ethyl 2-[2-[[3-chloro-6-(1,3-dioxo-4,5,6,7-tetrahydroisoindol-2-yl)-5-fluoro-2-pyridyl]oxy]phenoxy]acetate

[1073] ##STR00128##

[1074] To a solution of 630 mg (1.6 mmol) of compound 27 step 2 in 10 mL dimethylformamide was added 440 mg (3.2 mmol) of potassium carbonate and 0.21 mL (1.9 mmol) ethyl 2-bromoacetate (CAS 105-36-2). The mixture was stirred for 15 hours at 23 C. The mixture was diluted with water and extracted with methyl tert-butyl ether. The combined organic layer was washed with brine, dried over anhydrous Na.sub.2SO.sub.4, filtered and the solvent was removed under reduced pressure. The crude product was purified by column chromatography on silica (cyclohexane/ethyl acetate) to give 382 mg (0.8 mmol, 50%) of the desired compound 27.

[1075] [M+H]=475.0; Rt=1.292.

[1076] 1H-NMR (CDCl.sub.3, ppm): 7.71 (d, J=7.4 Hz, 1H), 7.21 (dd, J=7.8, 1.6 Hz, 1H), 7.16 (td, J=7.8, 1.6 Hz, 1H), 7.02 (td, J=7.7, 1.4 Hz, 1H), 6.90 (dd, J=8.1, 1.4 Hz, 1H), 4.57 (s, 2H), 4.17 (q, J=7.2 Hz, 2H), 2.38-2.29 (m, 4H), 1.76 (p, J=3.0 Hz, 4H), 1.22 (t, J=7.2 Hz, 3H).

B USE EXAMPLES

[1077] The herbicidal activity of the pyridylethers of formula (I) was demonstrated by the following greenhouse experiments:

[1078] The culture containers used were plastic flowerpots containing loamy sand with approximately 3.0% of humus as the substrate. The seeds of the test plants were sown separately for each species.

[1079] For the pre-emergence treatment, the active ingredients, which had been suspended or emulsified in water, were applied directly after sowing by means of finely distributing nozzles.

[1080] The containers were irrigated gently to promote germination and growth and subsequently covered with transparent plastic hoods until the plants had rooted. This cover caused uniform germination of the test plants, unless this had been impaired by the active ingredients.

[1081] For the post-emergence treatment, the test plants were first grown to a height of 3 to 15 cm, depending on the plant habit, and only then treated with the active ingredients which had been suspended or emulsified in water. For this purpose, the test plants were either sown directly and grown in the same containers, or they were first grown separately as seedlings and transplanted into the test containers a few days prior to treatment.

[1082] Depending on the species, the plants were kept at 10-25 C. or 20-35 C., respectively.

[1083] The test period extended over 2 to 4 weeks. During this time, the plants were tended, and their response to the individual treatments was evaluated.

[1084] Evaluation was carried out using a scale from 0 to 100. 100 means no emergence of the plants, or complete destruction of at least the aerial moieties, and 0 means no damage, or normal course of growth. A good herbicidal activity is given at values of at least 70 and a very good herbicidal activity is given at values of at least 85.

[1085] The plants used in the greenhouse experiments were of the following species:

TABLE-US-00014 Bayer code Scientific name ALOMY Alopecurus myosuroides AMARE Amaranthus retroflexus AVEFA Avena fatua CHEAL Chenopodium album ECHCG Echinocloa crus-galli POLCO Polygonum convolvulus SETVI Setaria viridis

[1086] At an application rate of 16 g/ha, the compounds (examples) 1, 8, 10, 12, 13, 15, 17, 19, 20, 22, 24 and 25 applied by the post-emergence method, showed very good herbicidal activity against AMARE, CHEAL, ECHCG and SETVI.

[1087] At an application rate of 16 g/ha, the compound (example) 2 applied by the post-emergence method, showed very good herbicidal activity against AMARE, ECHCG and SETVI.

[1088] At an application rate of 16 g/ha, the compound (example) 3, 4, 7 applied by the post-emergence method, showed good herbicidal activity against AMARE.

[1089] At an application rate of 16 g/ha, the compound (example) 5 applied by the post-emergence method, showed very good herbicidal activity against AMARE and CHEAL.

[1090] At an application rate of 16 g/ha, the compound (examples) 6, 21 applied by the post-emergence method, showed very good herbicidal activity against AMARE, CHEAL, SETVI and POLCO.

[1091] At an application rate of 16 g/ha, the compound (example) 9 applied by the post-emergence method, showed good herbicidal activity against CHEAL, ECHCG and SETVI.

[1092] At an application rate of 16 g/ha, the compound (example) 11 applied by the post-emergence method, showed very good herbicidal activity against CHEAL and good herbicidal activity against POLCO.

[1093] At an application rate of 16 g/ha, the compound (example) 14 applied by the post-emergence method, showed very good herbicidal activity against SETVI.

[1094] At an application rate of 16 g/ha, the compound (examples) 16 applied by the post-emergence method, showed very good herbicidal activity against AMARE, CHEAL and POLCO.

[1095] At an application rate of 16 g/ha, the compound (example) 18 applied by the post-emergence method, showed very good herbicidal activity against AMARE and good herbicidal activity against SETVI.

[1096] At an application rate of 16 g/h, the compound (example) 26 applied by the post-emergence method, showed very good herbicidal activity against AMARE, CHEAL, POLCO and SETVI.

[1097] At an application rate of 16 g/h, the compound (example) 27 applied by the post-emergence method, showed very good herbicidal activity against AMARE, CHEAL, ECHCG, POLCO and SETVI.

TABLE-US-00015 TABLE 10 Comparison of the herbicidal activity of example 28 of the present invention example 28 [00129] ( compound of formula (I), wherein R.sup.1 = F; R.sup.2 = Cl; R.sup.3, R.sup.4 = H; R.sup.5 = OR.sup.6 with R.sup.6 = CH.sub.3; n = 1; Q, W, X = O; Y = Y.sup.55 with R.sup.17 = CF.sub.3, R.sup.18 = CH.sub.3, R.sup.28 = H, A.sup.1 = O; and Z = Z-3 with R.sup.a, R.sup.b, R.sup.d and R.sup.e = H) and compound no. A2-11 known from JP 2001/270867 A2-11 [00130] post emergence control 7 days after treatment (greenhouse): cmpd no. compound example 28 A2-11 (JP 2001/270867) application rate [g/ha] 16 16 unwanted plants damages AVEFA 98 80 application rate [g/ha] 8 8 unwanted plants damages AVEFA 80 70 application rate [g/ha] 4 4 unwanted plants damages ALOMY 75 65 SETVI 95 85 application rate [g/ha] 2 2 unwanted plants damages ALOMY 70 60 SETVI 90 80

[1098] The data clearly demonstrate the superior herbicidal activity of the inventive compounds of formula (I) of the present invention over the compounds known from the prior art.

[1099] The replacement of the central phenyl ring by a pyridine ring leads to a much better herbicidal activity as achieved by the compound known from JP 2001/270867.