Herbicidal pyridazinone derivatives

Abstract

The present invention provides a compound of Formula (I) or an agronomically acceptable salt thereof, wherein: R.sup.2 is selected from the group consisting of (A1), (A2) and (A3) wherein X.sup.1 is N or CR.sup.7X.sup.2 is N or CR.sup.8X.sup.3 is N or CR.sup.9X.sup.4 is N or CR.sup.6R.sup.1, R.sup.3, R.sup.4, R.sup.5 R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are as defined herein. The invention further relates to herbicidal compositions which comprise a compound of Formula (I), and to their use for controlling weeds, in particular in crops of useful plants. ##STR00001##

Claims

1. A compound Formula (I): ##STR00228## or an agronomically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.3-alkyl, C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.3-alkyl-, and tetrahydropyranyl-; R.sup.2 is selected from the group consisting of A1, A2 and A3 ##STR00229## wherein X.sup.1 is N or CR.sup.7; X.sup.2 is N or CR.sup.8; X.sup.3 is N or CR.sup.9; X.sup.4 is N or CR.sup.6; R.sup.3 is selected from the group consisting of hydrogen, halo, nitro, amino, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.3alkoxy-, C.sub.3-C.sub.6cycloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkoxy-C.sub.1-C.sub.3-alkyl, C.sub.3-C.sub.6cycloalkyl-C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.6alkyl-S(O).sub.p-, C.sub.1-C.sub.6alkyl-S(O).sub.p-C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.6haloalkyl-S(O).sub.p-, C.sub.1-C.sub.3alkylamino, C.sub.1-C.sub.3dialkylamino and C.sub.1-C.sub.6haloalkyl-S(O).sub.p-C.sub.1-C.sub.3-alkyl; R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6alkylcarbonyl-, arylcarbonyl-, C.sub.1-C.sub.6alkoxycarbonyl-, C.sub.1-C.sub.6alkyl-S(O).sub.p-, C.sub.1-C.sub.6alkyl-S(O).sub.pcarbonyl- and aryl-S(O).sub.p-, wherein said aryl groups may be optionally substituted by one or more R.sup.11; R.sup.5 is selected from the group consisting of hydroxyl, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.6 alkoxy-, C.sub.2-C.sub.6 alkenyloxy-, C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.3-alkyl-, C.sub.1-C.sub.6 alkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6 alkoxy-C.sub.2-C.sub.6alkoxy-, C.sub.1-C.sub.6 alkoxy-C.sub.2-C.sub.6alkoxy-C.sub.1-C.sub.3alkyl-,C.sub.1-C.sub.6 haloalkoxy-, C.sub.1-C.sub.6 haloalkoxy-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkyl-S(O).sub.p-, C.sub.1-C.sub.6haloalkyl-S(O).sub.p-, aryl, aryl-S(O).sub.p-, heterocyclyl, heterocyclyl-S(O).sub.p-, aryloxy-, aryl-C.sub.2-C.sub.6alkyl-, aryl-C.sub.1-C.sub.6alkoxy-, heterocyclyloxy-, heterocyclyl-C.sub.1-C.sub.3alkoxy-C.sub.1-C.sub.3alkyl-, hydroxycarbonyl, hydroxycarbonyl-C.sub.1-C.sub.3 alkoxy-, C.sub.1-C.sub.3 alkoxycarbonyl-, C.sub.1-C.sub.3 alkoxycarbonyl-C.sub.1-C.sub.3 alkoxy-, C.sub.1-C.sub.3alkylamino-, C.sub.1-C.sub.3dialkylamino-, C.sub.1-C.sub.3 alkylamino-S(O).sub.p-, C.sub.1-C.sub.3 alkylamino-S(O).sub.p-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3 dialkylamino-S(O).sub.p-, C.sub.1-C.sub.3 dialkylamino-S(O).sub.p- C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3alkylaminocarbonyl-, C.sub.1-C.sub.3alkylaminocarbonyl-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3dialkylaminocarbonyl-, C.sub.1-C.sub.3 dialkylaminocarbonyl-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3alkylcarbonylamino-, C.sub.1-C.sub.3 alkyl-S(O).sub.p-amino-, C.sub.1-C.sub.3alkyl-S(O).sub.p-C.sub.1-C.sub.3alkylamino-, C.sub.1-C.sub.3alkyl-S(O).sub.p- aminoC.sub.1-C.sub.3alkyl-, cyano and nitro, wherein said heterocyclyls are five or six membered heterocyclyls containing from one to three heteroatoms each independently selected from the group consisting of oxygen, nitrogen and sulphur, and wherein the aryl or heterocyclyl components may be optionally substituted by one or more substituents selected from the group consisting of halo, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.6alkyl-S(O).sub.p-, phenyl, cyano and nitro; R.sup.6 and R.sup.9 are independently selected from the group consisting of hydrogen, hydroxyl, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.6 alkoxy-, C.sub.2-C.sub.6 alkenyloxy-, C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.3-alkyl-, C.sub.1-C.sub.6 alkoxyC.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6 alkoxy-C.sub.2-C.sub.6alkoxy-, C.sub.1-C.sub.6 alkoxy-C.sub.2-C.sub.6alkoxy-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6 haloalkoxy-, C.sub.1-C.sub.6 haloalkoxy-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.6alkyl-S(O).sub.p-, C.sub.1-C.sub.6haloalkyl-S(O).sub.p-, aryl, aryl-S(O).sub.p-, heterocyclyl, heterocyclyl-S(O).sub.p-, aryloxy-, aryl-C.sub.2-C.sub.6alkyl-, aryl-C.sub.1-C.sub.6alkoxy-, heterocyclyloxy-, heterocyclyl-C.sub.1-C.sub.3alkoxy-C.sub.1-C.sub.3alkyl-, hydroxycarbonyl, hydroxycarbonyl-C.sub.1-C.sub.3alkoxy-, C.sub.1-C.sub.3 alkoxycarbonyl-, C.sub.1-C.sub.3alkoxycarbonyl-C.sub.1-C.sub.3 alkoxy-, C.sub.1-C.sub.3alkylamino-, C.sub.1-C.sub.3dialkylamino-, C.sub.1-C.sub.3alkylamino-S(O).sub.p-, C.sub.1-C.sub.3 alkylamino-S(O).sub.p-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3 dialkylamino-S(O).sub.p-, C.sub.1-C.sub.3 dialkylamino-S(O).sub.p-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3alkylaminocarbonyl-, C.sub.1-C.sub.3alkylaminocarbonyl-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3dialkylaminocarbonyl-, C.sub.1-C.sub.3 dialkylaminocarbonyl-C.sub.1-C.sub.3alkyl-, C.sub.1-C.sub.3alkylcarbonylamino-, C.sub.1-C.sub.3 alkyl-S(O).sub.p-amino-, C.sub.1-C.sub.3alkyl-S(O).sub.p-C.sub.1-C.sub.3alkylamino-, C.sub.1-C.sub.3alkyl-S(O)p- aminoC.sub.1-C.sub.3alkyl-, cyano and nitro, wherein said heterocyclyls are five or six membered heterocyclyls containing from one to three heteroatoms each independently selected from the group consisting of oxygen, nitrogen and sulphur, and wherein the aryl or heterocyclyl components may be optionally substituted by one or more substituents selected from the group consisting of halo, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3 alkoxy, C.sub.1-C.sub.3 haloalkoxy, C.sub.1-C.sub.6alkyl-S(O).sub.p-, phenyl, cyano and nitro; R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl-, C.sub.1-C.sub.3 alkoxy-, C.sub.2-C.sub.3alkenyl-, C.sub.2-C.sub.3alkynyl-, C.sub.1-C.sub.3 haloalkyl- and C.sub.1-C.sub.3haloalkoxy-; and wherein R.sup.5 and R.sup.9 can together form a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more nitrogen and/or oxygen heteroatoms, the 5- or 6-membered ring being optionally substituted by one or more R.sup.12; or R.sup.6 and R.sup.9 can together form a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more hetereoatoms selected from the group consisting of nitrogen, oxygen and S(O).sub.2, the 5- or 6-membered ring being optionally substituted by one or more R.sup.12; or R.sup.6 and R.sup.8 can together form a saturated or unsaturated 5- or 6-membered carbocyclic or heterocyclic ring, said heterocyclic ring comprising one or more nitrogen heteroatoms, the 5- or 6-membered ring being optionally substituted by one or more R.sup.13; and R.sup.11 is selected from the group consisting of halo-, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3 haloalkyl and C.sub.1-C.sub.6alkoxy; R.sup.12 is selected from the group of hydrogen, cyano, halo-, oxy-, C.sub.1-C.sub.3alkylS(O)p-, C.sub.1-C.sub.3 alkyl, C.sub.2-C.sub.3alkenyl, C.sub.2-C.sub.3alkynyl, C.sub.1-C.sub.3 alkoxy and C.sub.1-C.sub.3 haloalkyl; R.sup.13 is selected from the group of hydrogen, cyano, halo-, C.sub.1-C.sub.3alkylS(O)p-, C.sub.1-C.sub.3 alkyl, C.sub.2-C.sub.3alkenyl, C.sub.2-C.sub.3alkynyl, morpholinyl- and C.sub.1-C.sub.3 haloalkyl; and =0, 1 or 2.

2. A compound according to claim 1, wherein R.sup.3 and/or R.sup.4 is hydrogen.

3. A compound according to claim 1, wherein R.sup.2 is selected from the group consisting of A1a, A1b, A1c, A1d, A1e, A1f, A1g, A1h, A2a, A2b, A3a A3b and A3 c: ##STR00230## ##STR00231## wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 and R.sup.13 are as defined previously and n is 0, 1, 2 or 3.

4. A compound according to claim 3, wherein R.sup.2 is A1a.

5. A compound according to claim 1, wherein R.sup.5 is selected from the group consisting of hydroxyl, halo, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6cycloalkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkoxyC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.6 alkoxy-C.sub.2-C.sub.6alkoxy-C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.6 haloalkoxyC.sub.1-C.sub.3alkyl, C.sub.1-C.sub.6alkyl-S(O).sub.p-, aryl, aryloxy, heterocyclyl-C.sub.1-C.sub.3alkoxy-C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3dialkylamino-, C.sub.1-C.sub.3alkyl-S(O).sub.p-amino-C.sub.1-C.sub.3dialkyl, cyano and nitro.

6. A compound according to claim 5, wherein R.sup.5 is selected from the group consisting of chloro, fluoro, methyl, trifluoromethyl, 2-fluoroethyl-, methoxyethoxymethyl-, trifluoromethoxymethyl-, methylS(O).sub.p-, aryl, isoxazolinyl, morpholinyl, methyl-S(O).sub.p-dimethylamino-, cyano and nitro, wherein the aryl or heterocyclyl components may be optionally substituted by one or more substituents selected from the group consisting of chloro, methyl or trifluoromethyl.

7. A compound according to claim 1, wherein R.sup.6 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkyl-S(O).sub.p-, C.sub.2-C.sub.6alkenyl and C.sub.2-C.sub.6alkynyl.

8. A compound according to claim 1, wherein R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.3 alkyl-.

9. A compound according to claim 1, wherein R.sup.9 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6alkyl-S(O).sub.p-, C.sub.2-C.sub.6alkenyl and C.sub.2-C.sub.6alkynyl.

10. A herbicidal composition comprising a herbicidal compound according to claim 1 and an agriculturally acceptable formulation adjuvant.

11. A herbicidal composition according to claim 10, further comprising at least one additional pesticide.

12. A herbicidal composition according to claim 11, wherein the additional pesticide is a herbicide or herbicide safener.

13. A method of controlling weeds at a locus comprising application to the locus of a weed controlling amount of a composition comprising a compound of Formula (I) as described in claim 1 or an agronomically acceptable salt thereof.

Description

EXAMPLES

(1) Examples of the synthesis of specific compounds of the present invention are provided below.

Example 1

5-[2-chloro-3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-phenyl]-4-hydroxy-2-propyl-pyridazin-3-one

(2) A mixture of 5-[2-chloro-3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-phenyl]-4-methoxy-2-propyl-pyridazin-3-one (692 mg, 1.62 mmol) in morpholine (1.42 ml) was heated to 100 C. for 1 h. The reaction mixture was cooled then dichloromethane (20 ml) and 2M hydrochloric acid (20 ml) were added and the mixture stirred for 30 mins. The dichloromethane layer was separated then the aqueous layer extracted twice with dichloromethane. The combined organic extracts were passed through a phase separation cartridge then concentrated in vacuo. The crude product was dissolved in ethyl acetate then precipitated with hexane, concentrated in vacuo and triturated with acetonitrile to give the product as an off-white solid (224.6 mg).

5-[2-chloro-3-(4,5-dihydroisoxazol-3-yl)-4-methylsulfonyl-phenyl]-4-methoxy-2-propyl-pyridazin-3-one

(3) A mixture of 5-chloro-4-methoxy-2-propyl-pyridazin-3-one (811 mg, 4 mmol), potassium acetate (589 mg, 6 mmol), bis(pinicolato)diboron (1.52 g, 6 mmol), tris(dibenzylideneacetone)dipalladium(0) (148 mg, 0.16 mmol) and tricyclohexylphosphine (180 mg, 0.64 mmol) in degassed dioxane (12 ml) was heated at 150 C. for 15 minutes under microwave irradiation. The mixture was allowed to cool to room temperature then filtered through Celite, eluting with ethyl acetate. The filtrate was evaporated under reduced pressure then used directly in the next step.

(4) The crude boronate ester was dissolved in degassed dimethoxyethane (12 ml); to the mixture were added 3-(3-bromo-2-chloro-6-methylsulfonyl-phenyl)-4,5-dihydroisoxazole (2.71 g, 8 mmol), caesium fluoride (2.43 g, 16 mmol) and [1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (260 mg, 0.32 mmol). The resulting mixture was heated at 150 C. for 20 minutes under microwave irradiation then allowed to cool to room temperature and filtered through Celite, eluting with ethyl acetate. The filtrate was concentrated under reduced pressure then purified by chromatography on silica eluting with 0-100% ethyl acetate in isohexane to give the product as a brown oil (692 mg).

(5) 8.06 (1H, d, J 8.1), 7.59 (1H, s), 7.56 (1H, d, J 8.1), 4.63 (3H, t, J 10.2), 4.19 (3H, s), 4.12 (2H, dd, J 7.3, 7.3), 3.47 (3H, t, J 10.2), 3.28 (3H, s), 1.90 (2H, m), 1.02 (3H, t, J 7.2)

5-chloro-4-methoxy-2-propyl-pyridazin-3-one

(6) To a stirred solution of 4,5-dichloro-2-propyl-pyridazin-3-one (7.31 g, 35.3 mmol) in dioxane (150 ml) was added a solution of sodium methoxide in methanol (25% wt in methanol, 8.6 ml, 38.8 mmol) dropwise and the mixture stirred at room temperature for 60 mins. Water (150 ml) was added and the mixture extracted with diethyl ether (3100 ml). The combined organics were dried, filtered and concentrated in vacuo.

(7) The crude product was purified by chromatography on silica eluting with ethyl acetate/hexanes to give the desired product as a colourless oil (5.44 g).

4,5-dichloro-2-propyl-pyridazin-3-one

(8) To a stirred solution of 4,5-dichloro-1H-pyridazin-6-one (8.25 g, 50 mmol) in N,N-dimethylformamide (25 ml) at room temperature was added potassium carbonate (1.2 g, 60 mmol) and 1-iodopropane (5.85 ml, 60 mmol). The mixture was stirred at 70 C for 2 hrs then water (75 ml) was added and the mixture extracted with dichloromethane (3100 ml). The combined organic extracts were dried, filtered and concentrated in vacuo then partitioned between brine (200 ml) and diethylether (200 ml). The organic layer was dried, filtered and concentrated in vacuo to give a brown oil. The crude product was purified by chromatography on silica eluting with ethyl acetate/hexanes to give the desired product as a colourless oil (7.31 g).

(9) 7.78 (1H, s), 4.20-4.11 (2H, m), 1.90-1.74 (2H, m), 0.96 (3H, t, J 7.2)

Example 2

4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one

(10) A mixture of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (48 mg, 0.132 mmol) in morpholine (2 ml) was heated to 100 C. for 3 hours. The reaction was then allowed to cool to room temperature and evaporated under reduced pressure. The resulting residue was dissolved in ethyl acetate and washed with 2M hydrochloric acid. The organic layer was then dried over sodium sulphate and evaporated. The resulting solid was triturated with dichloromethane/hexane to give the desired product as a pale pink solid (25 mg).

4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one

(11) To a solution of 4-methoxy-2-methyl-5-[2-methylsulfanyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (90 mg. 0.27 mmol) in acetic acid (4 ml) was added hydrogen peroxide (50% wt in water, 56 mg, 0.82 mmol) at room temperature. The reaction mixture was slowly heated to 55 C. and maintained at that temperature overnight. The reaction mixture was diluted with dichloromethane and quenched with sat. aq. sodium hydrogen carbonate and solid sodium hydrogen carbonate slowly until the pH was 6-7. The organic layer was separated and the aqueous phase extracted with dichloromethane. The combined organics were dried over sodium sulphate and evaporated to give the desired product (78 mg) as a pale yellow oil. This was used without further purification.

(12) .sub.H (CDCl.sub.3) 8.46 (1H, d), 7.98 (1H, dd), 7.60 (1H, s), 7.46 (1H, d), 4.14 (3H, s), 3.85 (3H, s), 3.02 (3H, s)

4-methoxy-2-methyl-5-[2-methylsulfanyl-4-(trifluoromethyl)phenyl]pyridazin-3-one

(13) A mixture of 5-chloro-4-methoxy-2-methyl-pyridazin-3-one (100 mg, 0.573 mmol), potassium acetate (84 mg, 0.86 mmol), bis(pinacolato)diboron (218 mg, 0.86 mmol), tris(dibenzylideneacetone)dipalladium(0) (4%, 21 mg, 0.023 mmol) and tricyclohexylphosphine (16%, 26 mg, 0.092 mmol) in degassed dioxane (2.5 ml) was heated at 150 C. for 15 min under microwave irradiation. The mixture was filtered through celite, washing with ethyl acetate and the filtrate evaporated under reduced pressure. The residue was dissolved in degassed 1,2-dimethoxyethane (2.5 ml) and 1-bromo-2-methylsulfanyl-4-(trifluoromethyl)benzene (233 mg, 0.86 mmol), caesium fluoride (348 mg, 2.29 mmol) and [1,1-bis(diphenylphosphino)-ferrocene]palladium(II)chloride, dichloromethane complex (8%, 38 mg, 0.046 mmol) were then added. The resulting mixture was heated at 160 C. for 15 min under microwave irradiation. The reaction mixture was filtered through celite, washing with ethyl acetate. The filtrate was evaporated under reduced pressure and the residue purified by chromatography on silica, eluting with 0-40% ethyl acetate in hexanes, to give the desired product (190 mg, containing some residual pinacol impurity) as a red oil. This was used without further purification.

(14) .sub.H (CDCl.sub.3) 7.52 (1H, s), 7.50 (1H, br s), 7.47 (1H, br d), 7.26 (1H, br d), 4.05 (3H, s), 3.84 (3H, s), 2.49 (3H, s)

5-chloro-4-methoxy-2-methyl-pyridazin-3-one

(15) To a stirred solution of 4,5-dichloro-2-methyl-pyridazin-3-one (19.7 g, 110 mmol) in 1,4-dioxane (550 ml) was added sodium methoxide (28.5 g, 132 mmol, 30.2 ml) dropwise and the resulting mixture stirred at room temperature for 1 hr. The reaction was quenched with water (500 ml) then extracted with diethyl ether (500 ml then 250 ml). The combined organics were dried, filtered and concentrated in vacuo to give 15.83 g of a white solid.

(16) .sub.H (CDCl.sub.3) 7.68 (1H, s), 4.28 (3H, s), 3.75 (3H, s)

4,5-dichloro-2-methyl-pyridazin-3-one

(17) To a stirred solution of 4,5-dichloro-1H-pyridazin-6-one (25.0 g, 152 mmol) in N,N-dimethylformamide (152 ml) was added potassium carbonate (25.4 g, 182 mmol) and iodomethane (25.8 g, 182 mmol, 11.3 ml). The resulting mixture was stirred at room temperature overnight. The reaction mixture was then poured onto ice-water (300 ml) and the mixture stirred for 15 mins. The resulting precipitate was collected by filtration, then dissolved in dichloromethane and passed through a phase separation cartridge. The organics were concentrated in vacuo to give 19.7 g of a pale brown solid.

(18) 1H NMR (400 MHz, Chloroform) d ppm 3.83 (s, 3H) 7.77 (s, 1H)

Example 3

4-hydroxy-2-methyl-5-[3-(m-tolyl)-2-oxo-4-(trifluoromethyl)-1-pyridyl]pyridazin-3-one

(19) A mixture of 4-chloro-2-methyl-5-[3-(m-tolyl)-2-oxo-4-(trifluoromethyl)-1-pyridyl]pyridazin-3-one (74 mg, 0.19 mmol) in aqueous potassium hydroxide (0.5M, 3 ml, 0.606 mmol) and methanol (2.5 ml) was heated at 55 C. for 90 minutes. Morpholine (1 ml) was added and reaction heated at 90 C. for 2 hours. The reaction mixture was concentrated under reduced pressure. 2M hydrochloric acid was then carefully added to the residue with rapid stirring for 5-10 min. The resulting cream precipitate was filtered, washed with 2M hydrochloric acid and water and then dried in a vacuum oven at 55 C. overnight to give the desired product (37 mg).

4-chloro-2-methyl-5-[3-(m-tolyl)-2-oxo-4-(trifluoromethyl)-1-pyridyl]pyridazin-3-one

(20) A mixture of 3-(m-tolyl)-4-(trifluoromethyl)-1H-pyridin-2-one (68 mg, 0.269 mmol), 4,5-dichloro-2-methyl-pyridazin-3-one (58 mg, 0.323 mmol) and potassium carbonate (112 mg, 0.807 mmol) in N,N-dimethylformamide (1 ml) was heated in the microwave at 150 C. for 25 min. The reaction mixture was then poured into 2M hydrochloric acid and extracted with ethyl acetate. The organic extracts were combined, dried over sodium sulphate and evaporated under reduced pressure. The crude mixture was purified by chromatography on silica, eluting with ethyl acetate in hexanes to give the desired product as a yellow oil (74 mg).

(21) .sub.H (CDCl.sub.3) 7.84 (1H, s), 7.34-7.22 (3H, m), 7.11 (2H, m), 6.63 (1H, d), 3.88 (3H, s), 2.38 (3H, s)

3-(m-tolyl)-4-(trifluoromethyl)-1H-pyridin-2-one

(22) A mixture of 2-chloro-3-(m-tolyl)-4-(trifluoromethyl)pyridine (96 mg, 0.353 mmol) and sodium hydroxide in dimethylsulphoxide (0.6 ml) and water (0.6 ml) was heated at 150 C. under microwave irradiation for 60 minutes. The liquid mixture was separated from the glassy residue and acidified to pH 1 with 2M hydrochloric acid. The resulting white precipitate was filtered, washed with a few drops of water and dried in a vacuum oven at 55 C. overnight to give the product as a white solid (68 mg).

(23) .sub.H (CD3OD) 7.62 (1H, d), 7.34-7.30 (1H, m), 7.25-7.23 (1H, m), 7.06 (1H, s), 7.02 (1H, d), 6.66 (1H, d), 2.40 (3H, s)

2-chloro-3-(m-tolyl)-4-(trifluoromethyl)pyridine

(24) A mixture of 2-chloro-3-iodo-4-methyl-pyridine (200 mg, 0.652 mmol), m-tolylboronic acid (132 mg, 0.976 mmol), tetrakis(triphenylphosphine) palladium(0) (8%, 60 mg, 0.052 mmol) and potassium carbonate (136 mg, 0.976 mmol) in 1,2-dimethoxyethane (2.8 ml) was heated at 150 C. for 30 min under microwave irradiation. The reaction mixture was poured into brine and extracted with ethyl acetate. The organic extracts were dried over sodium sulphate and evaporated. The crude mixture was purified by chromatography on silica, eluting with ethyl acetate in hexanes, to give the product as a colourless oil (96 mg).

2-chloro-3-iodo-4-methyl-pyridine

(25) n-Butyllithium (1.6M in hexanes, 13.3 ml, 21.3 mmol) was added dropwise to a solution of diisopropylamine (33 ml, 23.3 mmol) in tetrahydrofuran (7 ml) at 70 C. (internal temp) and the resulting mixture was stirred for 30 min. 2-Chloro-4-trifluoromethyl-pyridine (2.5 ml, 3.52 g, 19.4 mmol) was then added dropwise over 20 minutes and the mixture stirred for 2 hours at 70 C. This was then cannulated rapidly into a solution of iodine (5.2 g, 20.4 mmol) in tetrahydrofuran (3 ml) held at 0 C. The resulting mixture was stirred for 10 min, quenched with aqueous sodium metabisulfite and extracted with ethyl acetate. The organic layer was collected, washed with brine, dried over magnesium sulphate and evaporated. The crude mixture was purified by chromatography on silica, eluting with ethyl acetate in hexane, to give the desired compound (4.87 g, 82%) as a pale yellow solid contaminated with traces of starting material.

(26) .sub.H (CDCl.sub.3) 8.50 (1H, d), 7.44 (1H, d)

Example 4

2-cyclopentyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-pyridazin-3-one

(27) To a stirred solution of 4-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-5-methoxy-1H-pyridazin-6-one (126 mg, 0.35 mmol), triphenylphosphine (184 mg, 0.70 mmol) and cyclopentanol (0.06 ml, 0.70 mmol) in dry THF (3.5 ml) under a nitrogen atmosphere was added diisopropyl azodicarboxylate (0.14 ml, 0.7 mmol) dropwise. The resulting mixture was stirred at room temperature for 3 hours then concentrated in vacuo. The crude product was purified by column chromatography on silica, eluting with isohexane/ethyl acetate, to give 2-cyclopentyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-pyridazin-3-one (94 mg).

(28) 8.06 (1H, d, J 8.1), 7.56 (1H, s), 7.43 (1H, d, J 8.1), 5.50-5.41 (1H, m), 4.61 (2H, t, J 9.9), 4.10 (3H, s), 3.41 (2H, br s), 3.22 (3H, s), 2.17-2.02 (2H, m), 2.04 (3H, s), 2.00-1.86 (4H, m), 1.74-1.67 (2H, m)

4-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-5-methoxy-1H-pyridazin-6-one

(29) To a stirred solution of 5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-2-[(4-hydroxyphenyl)methyl]-4-methoxy-pyridazin-3-one (281 mg, 0.58 mmol) in acetonitrile (5 ml) and water (1 ml) at room temperature was added ceric ammonium nitrate and the mixture was stirred at room temperature. The reaction was monitored by LCMS.

(30) After 90 minutes, brine (25 ml) and ethyl acetate (25 ml) were added. The layers were separated and the aqueous layer extracted with ethyl acetate a further two times. The combined organics were washed with sat aqueous sodium bicarbonate (25 ml), then dried and concentrated in vacuo. The crude product was triturated with hexane (20 ml) and filtered to give 126 mg pale yellow solid.

(31) 8.08 (1H, d, J 8.1), 7.56 (1H, s), 7.44 (1H, d, J 8.1), 4.61 (2H, t, J 10.2), 4.19 (3H, s), 3.43 (2H, br s), 3.22 (3H, s), 2.19 (3H, s)

5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-2-[(4-hydroxyphenyl)methyl]-4-methoxy-pyridazin-3-one

(32) A mixture of 5-chloro-4-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one (281 mg, 1 mmol), palladium acetate (18 mg, 0.08 mmol), 3-[2-methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,5-dihydroisoxazole (548 mg, 1.5 mmol), aqueous tripotassium phosphate (0.4 ml. 2 mmol) and SPhos (66 mg, 0.16 mmol) in degassed toluene was heated at 150 C. for 30 minutes under microwave irradiation. The mixture was allowed to cool to room temperature then filtered through Celite, eluting with ethyl acetate. The filtrate was evaporated under reduced pressure, and then purified by column chromatography to give the desired product as a pink oil (281 mg).

(33) 8.00 (1H, d), 7.49 (1H, s), 7.41 (2H, d), 7.35 (1H, d), 6.86 (2H, d), 5.36-5.14 (2H, br d), 4.54 (2H, t), 4.07 (3H, s), 3.77 (3H, s), 3.34 (2H, br s), 3.18 (3H, s), 2.11 (3H, s)

(34) 3-[2-methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,5-dihydroisoxazole is prepared as described in example 7 below.

5-chloro-4-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one

(35) To a stirred solution of 4,5-dichloro-2-[(4-methoxyphenyl)methyl]pyridazin-3-one (5.70 g, 20 mmol) in dry dioxane (50 ml) was added the sodium methoxide solution (30 wt % soln. in methanol (5.4 M), 4.07 ml, 22 mmol) at room temperature. The resulting mixture was stirred at room temperature, monitoring by LCMS, and then poured into water (50 ml)/dichloromethane (50 ml). The organic layer was separated and the aqueous layer extracted with dichloromethane (250 ml). The combined organics were dried over magnesium sulphate and evaporated. The crude product was purified by column chromatography on silica, eluting with ethyl acetate/hexane, to give the desired product 5-chloro-4-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one as a white solid (4.53 g) together with the isomeric compound, 4-chloro-5-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one (650 mg).

(36) Nmr Data:

(37) 5-chloro-4-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one: 7.70 (1H, s), 7.39 (2H, d), 6.84 (2H, d), 5.20 (2H, s), 4.24 (3H, s), 3.79 (3H, s)

(38) 4-chloro-5-methoxy-2-[(4-methoxyphenyl)methyl]pyridazin-3-one: 7.80 (1H, s), 7.40 (2H, d), 6.86 (2H, d), 5.29 (2H, s), 4.02 (3H, s), 3.79 (3H, s)

(39) 4,5-dichloro-2-[(4-methoxyphenyl)methyl]pyridazin-3-one is prepared from 4,5-dichloro-1H-pyridazin-6-one by a procedure analogous to that described in example 1 above.

Example 5

5-[6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-hydroxy-2-methyl-pyridazin-3-one

(40) 5-[6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-methoxy-2-methyl-pyridazin-3-one (70 mg, 0.1976 mmol) was dissolved in acetonitrile (5 ml) and sodium iodide (50 mg, 0.33 mmol) was added in a 20 ml microwave tube. Chloro(trimethyl)silane (0.043 ml, 0.34 mmol) was added and the yellow reaction mixture immediately went purple. The mixture was stirred in a microwave vial at 100 C. for 30 minutes. LCMS showed only partial conversion to the desired product. More chloro(trimethyl)silane and sodium iodide were added and the reaction re-microwaved at 100 C. for 30 mins. LCMS showed an increase in the desired product but suggested the starting material was still the major component (60%). The mixture was poured into water, basified with 2M sodium hydroxide and extracted into dichloromethane. The organic extracts were passed through a phase separation cartridge and evaporated to yield the un-reacted starting material. The basic aqueous layer was acidified with 2M hydrochloric acid and extracted with dichloromethane. The organic extracts were passed through a second phase separation cartridge and evaporated to yield the desired product, 5-[6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-hydroxy-2-methyl-pyridazin-3-one (21 mg, 0.062 mmol) as a pink solid.

(41) 1H NMR (400 MHz, Chloroform) ppm d 1H 9.18, s 1H 8.35, dd 1H 7.98, s 1H 7.69, s 3H 3.90

5-[6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-methoxy-2-methyl-pyridazin-3-one

(42) [6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-trimethyl-stannane (200 mg, 0.528 mmol), 5-chloro-4-methoxy-2-methyl-pyridazin-3-one (105 mg, 0.60144 mmol), 1,4-bis(diphenylphosphinobutane)palladium dichloride (33 mg), copper(II) oxide (45 mg, 0.566 mmol) and N,N-dimethylformamide (5 ml, 64.4 mmol) were stirred in a microwave vial at 140 C. for 30 minutes. LCMS showed good conversion to the desired product with a minor amount of the homo-coupled by-product as well and several other small impurities. The reaction mixture was filtered through a very small silica plug. The filtrate was partitioned between ether and water. The organic extracts were separated, washed, dried over anhydrous magnesium sulphate and evaporated. The crude product was dissolved in dichloromethane and purified by column chromatography, eluting with ethyl acetate/iso-hexane) to give 5-[6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-4-methoxy-2-methyl-pyridazin-3-one (75 mg, 0.2117 mmol) as a yellow solid.

(43) 1H NMR (400 MHz, Chloroform) ppm d 1H 9.20, s 1H 8.20, dd 1H 7.92, s 1H 7.61, s 3H 4.14, s 3H 3.88

(44) 5-chloro-4-methoxy-2-methyl-pyridazin-3-one is prepared from 4,5-dichloro-1H-pyridazin-6-one as described in example 2.

[6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-trimethyl-stannane

(45) A mixture of 6-fluoro-3-iodo-2-(trifluoromethyl)-1,8-naphthyridine (400 mg, 1.17 mmol), hexamethyl ditin (1.15 g, 3.40 mmol) and bis(triphenylphosphine)palladium(II)dichloride (100 mg, 0.141 mmol) catalyst, in degassed 1,4-dioxane (6 mL, 70.3 mmol) was heated at 110 C. for 60 minutes under microwave irradiation. LCMS showed excellent conversion to the desired product. The reaction mixture was adsorbed on silica and purified by column chromatography, eluting with ethyl acetate/isohexane, to give [6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-yl]-trimethyl-stannane as a pale orange solid (300 mg, 0.7918 mmol).

(46) 1H NMR (400 MHz, Chloroform) ppm d 1H 9.10, s 1H 8.48, dd 1H 7.85, s 9H 0.47

(47) 6-fluoro-3-iodo-2-(trifluoromethyl)-1,8-naphthyridine can be prepared from 6-fluoro-2-(trifluoromethyl)-1,8-naphthyridin-3-amine by known procedures e.g. in J. Org. Chem. 1977, 42 (14), 2426-2431.

Example 6

4-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-1,3-dimethyl-4H-pyridazine-5,6-dione

(48) 4-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-1,3-dimethyl-4H-pyridazine-5,6-dione is prepared from 4,5-dichloro-2,6-dimethyl-pyridazin-3-one by a reaction sequence analogous to that in Example 1.

4,5-dichloro-2,6-dimethyl-pyridazin-3-one

(49) To a 20 ml microwave vial was added 6-bromo-4,5-dichloro-2-methyl-pyridazin-3-one (1.00 g, 3.88 mmol), [1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (0.032 g, 0.039 mmol), caesium carbonate (2.02 g, 6.20 mmol), trimethylboroxine (0.787 g, 6.20 mmol, 0.876 mL) and 1,4-dioxane (9 mL) and heated in the microwave at 100 C. for 1 hour then for a further 30 minutes at 150 C.

(50) The reaction mixture was filtered through celite, silica added and reduced under vacuum. The residue was purified by chromatography on silica, eluting with 0-30% ethyl acetate/hexane to give a white solid containing a 9:1 ratio of the desired product, 4,5-dichloro-2,6-dimethyl-pyridazin-3-one, together with a byproduct, 5-chloro-2,4,6-trimethyl-pyridazin-3-one (502 mg in total). This mixture was used directly in the next step to form 5-chloro-4-methoxy-2,6-dimethyl-pyridazin-3-one, as the by-product does not react.

(51) 1H NMR (CDCl.sub.3):

(52) 4,5-dichloro-2,6-dimethyl-pyridazin-3-one 3.79 (s, 3H), 2.44 (s, 3H) 5-chloro-2,4,6-trimethyl-pyridazin-3-one 3.73 (s, 3H), 2.38 (s, 3H), 2.29 (s, 3H)

Example 7

2-cyclopropyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-hydroxy-pyridazin-3-one

(53) A solution of 2-cyclopropyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-pyridazin-3-one (0.203 g, 0.5032 mmol) in morpholine (0.4384 g, 5.032 mmol, 0.440 ml) was heated at 100 C. for 1 hour.

(54) The reaction mixture was allowed to cool to room temperature then diluted with dichloromethane (5 ml) and 2M hydrochloric acid (5 ml). The mixture was then stirred for 30 mins.

(55) The organic layer was separated and the aqueous layer extracted with dichloromethane (25 ml). The combined organics were dried and concentrated in vacuo to give a pink solid.

(56) The crude solid was triturated with acetonitrile (32 ml portions) and collected by filtration to give 2-cyclopropyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-hydroxy-pyridazin-3-one as a white solid (0.0883 g).

(57) 1H NMR (400 MHz, Chloroform) ppm 1.05-1.12 (m, 2H) 1.22-1.29 (m, 2H) 2.23 (s, 3H) 3.21 (s, 3H) 3.39 (br. s., 2H) 4.19 (dt, J=7.65, 3.69 Hz, 1H) 4.60 (t, J=10.07 Hz, 2H) 7.49 (d, J=8.19 Hz, 1H) 7.60 (s, 1H) 8.08 (d, J=8.19 Hz, 1H)

2-cyclopropyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-pyridazin-3-one

(58) A mixture of 5-chloro-2-cyclopropyl-4-methoxy-pyridazin-3-one (0.20 g, 1 mmol), 3-[2-methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,5-dihydroisoxazole (0.438 g, 1.2 mmol), palladium (II) acetate (0.018 g, 0.08 mmol), tripotassium phosphate (1.026 g, 2 mmol, 0.4 ml, 5 mol/l) and SPhos (0.0670 g, 0.16 mmol) in toluene (3.46 g, 37.4 mmol, 4.0 ml) was heated at 150 C. for 30 minutes under microwave irradiation.

(59) The reaction mixture was filtered through celite, eluting with ethyl acetate. The filtrate was concentrated in vacuo to give the crude product. The crude product was dryloaded onto silica and purified by chromatography to give 2-cyclopropyl-5-[3-(4,5-dihydroisoxazol-3-yl)-2-methyl-4-methylsulfonyl-phenyl]-4-methoxy-pyridazin-3-one as a colourless oil (0.203 g, 0.503 mmol).

(60) 1H NMR (400 MHz, Chloroform) ppm 1.03-1.11 (m, 2H) 1.19 (br. s., 2H) 2.18 (s, 3H) 3.22 (s, 3H) 3.40 (br. s., 2H) 4.14 (s, 4H) 4.60 (t, J=10.07 Hz, 3H) 7.41 (d, J=8.19 Hz, 1H) 7.48 (s, 1H) 8.06 (d, J=8.19 Hz, 1H)

3-[2-methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,5-dihydroisoxazole

(61) A mixture of 3-(3-bromo-2-methyl-6-methylsulfonyl-phenyl)-4,5-dihydroisoxazole (A, 3.182 g, 10 mmol), bis(pinacolato)diboron (3.8476 g, 15 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.092 g, 0.1 mmol), S-Phos (0.168 g, 0.4 mmol) and potassium acetate (1.487 g, 15 mmol) in 1,4-dioxane (15.51 g, 176 mmol, 15 ml) was heated at 150 C for 30 mins under microwave irradiation. The crude mixture was filtered through a pad of celite eluting with ethyl acetate. The crude product was dry loaded onto silica and purified by chromatography to give 3-[2-methyl-6-methylsulfonyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4,5-dihydroisoxazole as a pale yellow solid. (2.06 g, 5.64 mmol)

(62) 1H NMR (400 MHz, Chloroform) ppm 1.37 (s, 13H) 2.52 (s, 3H) 3.16 (s, 4H) 3.33 (br. s., 2H) 4.57 (t, J=10.00 Hz, 2H) 7.94 (d, J=8.06 Hz, 1H) 7.99 (d, J=7.92 Hz, 1H)

(63) 3-(3-bromo-2-chloro-6-methylsulfonyl-phenyl)-4,5-dihydroisoxazole can be prepared as reported for example in DE 19820722.

5-chloro-2-cyclopropyl-4-methoxy-pyridazin-3-one

(64) To a stirred solution of 4,5-dichloro-2-cyclopropyl-pyridazin-3-one (A, 0.599 g, 2.9214 mmol, 100 mass %) in 1,4-dioxane (100 mL, 100 mass %) was added sodium methoxide (0.69443 g, 3.2135 mmol, 0.735 mL, 25 mass %) dropwise and the resulting mixture stirred at room temperature for 1 hour. The reaction mixture was concentrated in vacuo to give a crude brown oil then dry loaded onto silica and purified by chromatography to give 5-chloro-2-cyclopropyl-4-methoxy-pyridazin-3-one as a white solid (0.498 g).

(65) 1H NMR (400 MHz, Chloroform) ppm 0.96-1.14 (m, 4H) 3.95-4.07 (m, 1H) 4.28 (s, 3H) 7.64 (s, 1H)

4,5-dichloro-2-cyclopropyl-pyridazin-3-one

(66) A mixture of tert-butyl N-(tert-butoxycarbonylamino)-N-cyclopropyl-carbamate (0.68 g, 2.5 mmol) and mucochloric acid (0.43 g, 2.5 mmol) in hydrochloric acid (4 mol/l) in water (25 mmol, 6.3 ml) was heated at reflux for 6 hours. The reaction mixture was allowed to cool to room temperature then extracted with dichloromethane (310 ml). The combined organic extracts were dried and concentrated in vacuo. The crude product was purified by chromatography to give 4,5-dichloro-2-cyclopropyl-pyridazin-3-one as a white solid (0.353 g).

(67) 1H NMR (400 MHz, Chloroform) ppm 1.02-1.17 (m, 4H) 4.09-4.16 (m, 1H) 7.72 (s, 1H)

Tert-butyl N-(tert-butoxycarbonylamino)-N-cyclopropyl-carbamate

(68) To a stirred suspension of magnesium (1.34 g, 55 mmol) and catalytic iodine in tetrahydrofuran (5 ml) was added 5 ml of a 45 ml solution of cyclopropyl bromide (4.0 ml) in tetrahydrofuran (50 ml). The mixture was heated to initiate Grignard formation then the remaining solution of cyclopropyl bromide was added dropwise over 30 mins with heating (70 C). The Grignard solution was heated at reflux for a further 30 minutes then cooled to 0 C.

(69) To a stirred solution of di-tert-butyl azodicarboxylate in THF (50 ml) at 78 C. was added the solution of cyclopropylmagnesium bromide dropwise via cannula. The resulting solution was stirred at 78 C. for 30 mins then quenched with acetic acid. The mixture was allowed to warm to room temperature then water (150 ml) was added and the mixture extracted three times with diethyl ether. The combined organic extracts were dried, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica, eluting with ethyl acetate/hexane, to give the product as a white solid (6.68 g).

(70) 1H NMR (400 MHz, Chloroform) ppm 0.7 (4H, br s), 1.5 (18H, s), 2.9-3.0 (1H, br m), 6.1 and 6.4 (1H, br s)

Example 8

[2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]acetate

(71) To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dry dichloromethane (1 ml) at room temperature was added pyridine (0.03 g, 0.03 ml, 0.37 mmol) and 4-(dimethylamino)pyridine (0.35 mg, 0.0029 mmol). The mixture was stirred for 2 min and acetyl chloride (0.027 g, 0.025 ml, 0.345 mmol) was added dropwise. The resulting suspension was stirred at room temperature for 2 hours, then diluted with dichloromethane and washed successively with 2M hydrochloric acid and saturated aqueous sodium hydrogen carbonate. The organic layer was collected, passed through a phase-separation cartridge and the filtrate evaporated.

(72) The crude residue was purified by flash chromatography (10-55% ethyl acetate in hexanes, 13 min, then 3 min at 55%, 4 g silica GOLD) to give [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]acetate (0.095 g, 0.2434 mmol, 84.78% yield) as a white solid.

(73) 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one was prepared as described in Example 2.

Example 9

Methyl [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]carbonate

(74) To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dry toluene (1.99 g, 2.3 ml, 21.5 mmol) at room temperature was added triethylamine (0.032 g, 0.044 ml, 0.31 mmol), followed by methyl chloroformate (0.03 g, 0.024 ml, 0.31 mmol). The resulting mixture was stirred overnight.

(75) Water was added and the mixture extracted with ethyl acetate. The organic extracts were passed through a phase-separation cartridge and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (0-50% Ethyl acetate in hexanes, 12 min, then 3 minutes at 50%, 4 g silica) to give methyl [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]carbonate (0.113 g, 0.2781 mmol, 96.87% yield) as a white solid.

(76) 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one was prepared as described in Example 2.

Example 10

[2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]ethylsulfanylformate

(77) To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulphonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dry tetrahydrofuran (4.6 g, 5.17 ml, 63.7 mmol) at room temperature was added triethylamine (0.059 g, 0.08 ml, 0.57 mmol) followed by ethyl chlorothioformate (0.047 g, 0.039 ml, 0.36 mmol). The resulting suspension was stirred at room temperature for 90 minutes and then diluted with ethyl acetate and washed with brine. The organic phase was collected and passed through a phase-separation cartridge. The filtrate was evaporated and the residue was purified by flash chromatography (0-40% ethyl acetate in hexanes, 13 min, then 3 min at 40%, 4 g silica) to give [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]ethylsulfanylformate (0.126 g, 0.289 mmol, 100% yield) as a white solid.

(78) 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one was prepared as described in Example 2.

Example 11

[2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]propane-1-sulfonate

(79) To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.29 mmol) in dichloromethane (1.14 g, 0.86 ml, 13.4 mmol) at room temperature was added a solution of potassium carbonate (0.06 g, 0.43 mmol) in water (0.86 g, 0.86 ml, 47.81 mmol) followed by a solution of 1-propanesulphonyl chloride (0.063 g, 0.05 ml, 0.43 mmol) in dichloromethane (0.2 ml). Benzyltrimethylammonium chloride (0.0027 g, 0.0025 ml, 0.014 mmol) was then added and the biphasic mixture stirred vigorously at room temperature overnight.

(80) The reaction mixture was diluted with water/dichloromethane and the organic phase separated. The aqueous layer was extracted with dichloromethane. The combined organic extracts were washed with aqueous 2M hydrochloric acid and brine and then passed through a phase-separation cartridge. The filtrate was evaporated and the residue purified by flash chromatography (0-50% ethyl acetate in hexanes, 13 min, 4 g silica) to afford [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]propane-1-sulfonate (0.1 g, 0.22 mmol, 76.7% yield) as a white solid.

(81) 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one was prepared as described in Example 2.

Example 12

[2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]propane-1-sulfonate

(82) To a suspension of 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.1 g, 0.2871 mmol) and para-toluene sulphonyl chloride (0.061 g, 0.32 mmol) in dry acetonitrile (4.51 g, 5.7 ml, 110 mmol) at room temperature was added potassium carbonate (0.071 g, 0.52 mmol). The resulting suspension was stirred at room temperature overnight.

(83) The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extracts were passed through a phase-separation cartridge and the filtrate evaporated. The resulting solid was dissolved in minimum amount of dichloromethane and hexane was added dropwise with rapid stirring until precipitation. The precipitate was collected by filtration and dried under suction to afford [2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-3-oxo-pyridazin-4-yl]4-methylbenzenesulfonate (0.10 g, 0.2 mmol, 70.0% yield) as a white solid.

(84) 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one was prepared as described in Example 2.

Example 13

4-hydroxy-2-methyl-5-[4-morpholino-2-(trifluoromethyl)pyrimidin-5-yl]pyridazin-3-one

(85) 5-[4-chloro-2-(trifluoromethyl)pyrimidin-5-yl]-4-methoxy-2-methyl-pyridazin-3-one (240.0 mg, 0.22 mmol) was dissolved in morpholine (2.5 ml, 28.6 mmol). The reaction was stirred at 100 C. for 45 minutes. The reaction mixture was carefully added to 30.0 ml water and stirred for 10 minutes. The aqueous layer was extracted with dichloromethane (220 m). The aqueous layer was then acidified with aqueous hydrochloric acid (2.0M) and then washed with dichloromethane, which was collected using a phase-separation cartridge. The solvent was concentrated in vacuo and the crude was triturated with 5.0 ml acetonitrile then sonicated and the resulting solid (40.0 mg) was collected by filtration. TLC showed some impurity so it was triturated once more using 5.0 ml methanol and the resulting precipitate was isolated to yield 4-hydroxy-2-methyl-5-[4-morpholino-2-(trifluoromethyl)pyrimidin-5-yl]pyridazin-3-one (25.0 mg, 0.07 mmol, 31.2% yield) as a white solid.

5-[4-chloro-2-(trifluoromethyl)pyrimidin-5-yl]-4-methoxy-2-methyl-pyridazin-3-one

(86) 4-methoxy-2-methyl-5-[6-oxo-2-(trifluoromethyl)-1H-pyrimidin-5-yl]pyridazin-3-one 515.0 mg, 1.7 mmol) was dissolved in phosphorus (V) oxychloride (5.0 ml, 53 mmol). The mixture stirred at 85 C. for 90 minutes. The reaction was then stopped, and let to cool to room temperature and was then concentrated in vacuo. The crude product was dropped into ice cold water and the aqueous layer extracted with dichloromethane. The organic layers were combined, dried over sodium sulphate, filtrate and concentrated in vacuo, then was purified using a 24 g silica cartridge eluting with iso-hexane:ethyl acetate (100:0.fwdarw.60:40 over 12 minutes then keeping the gradient for 6 minutes). The fractions containing product were concentrated in vacuo to yield 5-[4-chloro-2-(trifluoromethyl)pyrimidin-5-yl]-4-methoxy-2-methyl-pyridazin-3-one (240.0 mg, 0.22 mmol, 13.18% yield) as a translucent oil.

(87) .sup.1H NMR (400 MHz, Chloroform) ppm=3.86 (3H, s) 4.29 (3H, s) 7.63 (1H, s) 8.76 (1H, s)

4-methoxy-2-methyl-5-[6-oxo-2-(trifluoromethyl)-1H-pyrimidin-5-yl]pyridazin-3-one

(88) 2,2,2-Trifluoroacetamidine (450 mg, 11.8 mmol) was suspended in methanol (3.0 ml). Then methyl (E)-3-methoxy-2-(5-methoxy-1-methyl-6-oxo-pyridazin-4-yl)prop-2-enoate (1.00 g, 3.93 mmol) was added, followed by sodium methoxide (1.35 ml, 5.90 mmol). The mixture was heated to 65 C. for 2 hours.

(89) More 2,2,2-trifluoroacetamidine (450.0 mg, 11.8 mmol) and sodium methoxide (1.35 ml, 5.90 mmol) were added and the mixture stirred for another 2 hours. The reaction was stopped and let to cool to room temperature. 2M aqueous hydrochloric acid was added and the mixture was concentrated in vacuo.

(90) The crude product was purified by chromatography on silica, eluting with iso-hexane:ethyl acetate then with dichloromethane:methanol. The fractions containing product were combined and concentrated in vacuo to yield 4-methoxy-2-methyl-5-[6-oxo-2-(trifluoromethyl)-1H-pyrimidin-5-yl]pyridazin-3-one (520.0 mg, 1.72 mmol, 43.7% yield) as a pale yellow solid.

(91) .sup.1H NMR (400 MHz, d.sub.3-Methanol) ppm=3.80 (3H, s) 4.01 (3H, s) 7.94 (1H, s) 8.13 (1H, s)

Methyl (E)-3-methoxy-2-(5-methoxy-1-methyl-6-oxo-pyridazin-4-yl)prop-2-enoate

(92) 4-methoxy-2-methyl-5-tributylstannyl-pyridazin-3-one (2.9 g, 6.8 mmol) and methyl (Z)-2-iodo-3-methoxy-prop-2-enoate (1.5 g, 6.2 mmol) were dissolved in N,N-dimethylformamide (15.0 ml, 193 mmol). Caesium fluoride (1.9 g, 2.0 equiv., 12 mmol) was added and the mixture degassed with nitrogen. Copper iodide (0.12 g, 0.62 mmol) and palladium (0) tetrakis(triphenylphosphine) (0.36 g, 0.31 mmol) were then added and the mixture degassed another time with nitrogen before being put in a 55 C. pre-heated heating block for 2 hours.

(93) Water (50 ml) and dichloromethane (50 ml) were added and the reaction shaken vigorously. 50.0 ml Saturated aqueous sodium hydrogen carbonate was added and the mixture shaken again. The dichloromethane layer was collected and concentrated in vacuo. The crude product was dry-loaded onto a 120 g silica cartridge eluting with dichloromethane:ethyl acetate (100:0.fwdarw.40:60 over 20 minutes, then keeping the gradient for another 10 minutes). The fractions containing product were combined and concentrated in vacuo to yield a 1.12 g brown oil that solidified upon standing. The crude product was further purified by column chromatography on silica, eluting with iso-hexane:ethyl acetate (60:40.fwdarw.30:70 over 8 minutes then keeping the gradient for 5 minutes then going to 100% ethyl acetate). The fractions containing product were combined and concentrated in vacuo to yield the product as a pale yellow solid (882.0 mg, 56% yield).

(94) .sup.1H NMR (400 MHz, Chloroform, (12wq161h2)) ppm=3.74 (3H, s) 3.77 (3H, s) 3.90 (3H, s) 4.11 (3H, s) 7.52 (1H, s) 7.56 (1H, s)

4-methoxy-2-methyl-5-tributylstannyl-pyridazin-3-one

(95) To a stirred solution of 5-bromo-4-methoxy-2-methyl-pyridazin-3-one (5.00 g, 22.8 mmol) in tetrahydrofuran (40.6 g, 560 mmol, 45.7 ml) at 40 C was added 2-mesitylmagnesium bromide (1.0 mol) in tetrahydrofuran (46 g, 45.7 mmol, 46 ml, 1.0 mol/L) dropwise via a dropping funnel (maintaining the internal temperature below 30 C at all times) and the mixture stirred at 40 C for 30 minutes. Tri-n-butyltin chloride (23.2 g, 68.5 mmol, 19.3 ml) was then added dropwise as a solution in tetrahydrofuran (20 ml) and the mixture allowed to warm to 0 C over 1 hr.

(96) The reaction mixture was then quenched with saturated aqueous ammonium chloride solution (100 ml) and extracted with ethyl acetate (3100 mL). The combined organic extracts were dried, filtered and concentrated in vacuo to give the crude product.

(97) The crude product was dry loaded onto silica and purified by chromatography to give 4-methoxy-2-methyl-5-tributylstannyl-pyridazin-3-one as a reddish oil (5.21 g, 12.1 mmol, 53.2% yield)

(98) .sup.1H NMR (400 MHz, Chloroform) ppm 7.56 (1H, s) 4.14 (3H, s) 3.78 (3H, s) 1.44-1.62 (6H, m) 1.27-1.38 (6H, m) 1.00-1.21 (6H, m) 0.89 (9H, t, J=7.3 Hz)

(99) 5-bromo-4-methoxy-2-methyl-pyridazin-3-one may be prepared by a route analogous to that in Reaction Scheme 3.

Example 14

3-cyclohexyl-2-(3-fluorophenyl)-5-(5-hydroxy-1-methyl-6-oxo-pyridazin-4-yl)pyrimidin-4-one

(100) 3-cyclohexyl-2-(3-fluorophenyl)-5-(5-methoxy-1-methyl-6-oxo-pyridazin-4-yl)pyrimidin-4-one (51.0 mg, 0.118 mmol) was dissolved in morpholine (2.0 ml, 23 mmol. The reaction was stirred at 95 C. for 2 hours. LC indicated no reaction, so temperature was increased to 105 C. and the reaction stirred for a further 2 hours. This time, reaction had gone to completion so it the mixture was allowed to cool to room temperature. Aqueous hydrochloric acid was then added carefully to the reaction mixture until the mixture was acidic. The aqueous layer was washed with dichloromethane and the organic layers were combined and passed through a phase separation cartridge. The solvent was concentrated in vacuo and the crude triturated with 3.0 ml acetonitrile, sonicating the solution for about 1 minute.

(101) The solid was collected by filtration to yield the product as a pale pink solid (25.0 mg, 53.4% yield).

3-cyclohexyl-2-(3-fluorophenyl)-5-(5-methoxy-1-methyl-6-oxo-pyridazin-4-yl)pyrimidin-4-one

(102) Ethyl 3-fluorobenzenecarboximidate hydrochloride (135.0 mg, 0.6629 mmol) was suspended in methanol (3.0 ml). Then cyclohexanamine (0.066 g, 0.6629 mmol) was added and the mixture stirred for 2 hours at for 18 hours. The reaction was heated gradually to reflux and stirred for another 2 hours. More cyclohexylamine (0.066 g, 0.6629 mmol) was added and the mixture stirred at reflux for 2 hours. The reaction was stopped and concentrated in vacuo to yield an oil.

(103) The crude product was re-dissolved in methanol (3.0 ml), then sodium methoxide (0.12 g, 0.57 mmol) was added and the mixture stirred for 5 minutes before methyl (E)-3-methoxy-2-(5-methoxy-1-methyl-6-oxo-pyridazin-4-yl)prop-2-enoate (145.0 mg, 0.57 mmol) was then added and the mixture stirred at 65 C. for 3 hours.

(104) The reaction was cooled and the solvent was concentrated in vacuo, then the crude product was taken up in diethyl ether. The organic layer was washed with saturated sodium hydrogen carbonate, and the aqueous washed with diethyl ether. The organic phases were combined, dried over sodium sulphate, filtered and concentrated in vacuo, then was purified by chromatography on silica, eluting with iso-hexane:ethyl acetate to give the product (95 mg) as a pale yellow gum. This was further purified by preparative HPLC and concentrated in vacuo to give the product as a translucent oil (51.0 mg, 21.8% yield).

(105) .sup.1H NMR (400 MHz, Chloroform) ppm=0.93-1.11 (2H, m) 1.14-1.30 (1H, m) 1.57 (1H, d, J=12.9 Hz) 1.72 (2H, d, J=11.3 Hz) 1.81 (2H, d, J=13.4 Hz) 2.63-2.79 (2H, m) 3.81 (3H, s) 3.87-3.97 (1H, m) 4.21 (3H, s) 7.21-7.26 (1H, m) 7.27-7.30 (1H, m) 7.52 (1H, td, J=7.9, 5.6 Hz) 7.88 (1H, s) 8.07 (1H, s)

(106) Methyl (E)-3-methoxy-2-(5-methoxy-1-methyl-6-oxo-pyridazin-4-yl)prop-2-enoate was prepared as described in Example 13 above.

Example 15

4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-propoxy-pyridazin-3-one

(107) 4-hydroxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-propoxy-pyridazin-3-one can be prepared from 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-propoxy-pyridazin-3-one was prepared by a method analogous to that described in, for example, Example 1, step 1.

4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-propoxy-pyridazin-3-one

(108) To a mixture of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-1H-pyridazine-3,6-dione (0.09 g, 0.24 mmol) and potassium carbonate (0.17 g, 1.19 mmol) in N,N-dimethylformamide (1.4 g, 1.5 ml, 19 mmol) at room temperature was added 1-iodopropane (0.045 g, 0.026 ml, 0.26 mmol). The resulting yellow mixture was stirred for 3 hours and then poured into water and extracted with ethyl acetate. The organic extracts were washed with brine, filtered through a phase-separation cartridge and the filtrate evaporated. The crude residue was purified by flash chromatography (30-80% ethyl acetate in hexanes, 13 min, 4 g silica) to give 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-propoxy-pyridazin-3-one as a pale yellow oil (0.099 g, 0.236 mmol, 99.0% yield).

(109) 1H NMR (400 MHz, CDCl.sub.3): 8.41 (1H, br d), 7.94 (1H, br dd), 7.39 (1H, d), 4.10 (3H, s), 4.04-4.00 (2H, m), 3.72 (3H, s), 2.99 (3H, s), 1.57-1.52 (2H, m), 0.76 (3H, t).

4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-1H-pyridazine-3,6-dione

(110) To a solution of sodium nitrite (0.11 g, 1.6 mmol) in concentrated sulphuric acid (3 ml) at 0 C. was added dropwise a suspension of 6-amino-4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]pyridazin-3-one (0.51 g, 1.352 mmol) in glacial acetic acid (6.294 g, 6 ml, 105 mmol). The resulting mixture was allowed to warm to room temperature and stirred for 40 min. It was then cooled to 0 C. and water (9 ml) was added dropwise. The resulting suspension was stirred for 60 minutes at room temperature, then diluted with water (10 ml) and the precipitate collected by filtration, washed with water and dried in a vacuum oven at 55 C. overnight to afford 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-1H-pyridazine-3,6-dione as an off-white solid (0.35 g, 0.92 mmol, 68.25% yield).

(111) 1H NMR (400 MHz, MeOD): 8.38 (1H, br d), 8.08 (1H, br dd), 7.62 (1H, d), 3.95 (3H, s), 3.67 (3H, s), 3.14 (3H, s)

6-amino-4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-pyridazin-3-one

(112) To a solution of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-nitro-pyridazin-3-one (0.8 g, 1.964 mmol) in ethanol (19.7 g, 25 ml, 411 mmol) at 80 C. was added ammonium formate (2.502 g, 39.28 mmol) and palladium hydroxide on carbon (0.5517 g, 3.928 mmol). The resulting black mixture was maintained at 80 C. for 1 h (NB Sublimation of ammonium formate observed) and then hot-filtered through a short pad of celite, washing with hot ethanol, ethyl acetate and methanol. The filtrate was evaporated and the resulting residue rapidly stirred with water for 10 min and then collected by filtration and dried in a vacuum oven at 55 C. over 2 d (weekend).

(113) Yield: 510 mg (69%, yellow solid)

(114) 1H NMR (400 MHz, MeOD): 8.42 (1H, br s), 8.14 (1H, br d), 7.65 (1H, d), 3.94 (3H, s), 3.66 (3H, s), 3.16 (3H, s)

4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-nitro-pyridazin-3-one

(115) To a solution of 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-pyridazin-3-one (1.81 g, 5.00 mmol) in sulphuric acid (14.7 g, 8 ml, 138 mmol) at 0 C. was added dropwise nitric acid (1.26 g, 0.891 ml, 20.0 mmol). The resulting solution was stirred at 0 C. for 5 min, then allowed to warm to room temperature for 15 min and then heated to 50 C. for a further 2.5 hours. More nitric acid (1.26 g, 0.891 ml, 20.0 mmol) was added and heating continued for a further 2 h. LC-MS still showed presence of starting material. More nitric acid (1.26 g, 0.891 ml, 20.0 mmol) was added and heating continued for a further 1 hour. The reaction mixture was allowed to cool to room temperature and then carefully poured into ice-cold water with rapid stirring. The resulting pale yellow precipitate was filtered, washed with ice-cold water and then dried in a vacuum oven overnight at 55 C.

(116) It was found that the crude product had some acid contaminant. The orange solid was dissolved in dichloromethane and the organic phase washed with water (with a few drops of aqueous sodium hydroxide addedpH 14) and then passed through a phase-separation cartridge. The filtrate was evaporated under reduced pressure to give 4-methoxy-2-methyl-5-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]-6-nitro-pyridazin-3-one (0.8 g, 1.96 mmol, 39.3% Yield) as a pale pink solid.

(117) 1H NMR (400 MHz, CDCl.sub.3): 8.38 (1H, br s), 7.98 (1H, dd), 7.41 (1H, d), 4.20 (3H, s), 3.92 (3H, s), 3.00 (3H, s)

Example 16

4-hydroxy-2-methyl-5-[1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]pyridazin-3-one

2-methoxy-6-(trifluoromethyl)pyridine

(118) To a solution of 6-(trifluoromethyl)pyridin-2-ol (10.0 g, 10.0 g, 61.3 mmol) in dichloromethane (3 ml/mmol, 184 ml) was added silver carbonate (22.8 g, 82.8 mmol, 3.75 mL) and iodomethane (87.0 g, 613 mmol, 38.2 mL) and stirred in the dark for 24 hours. The reaction mixture was then filtered through Celite and washed with dichloromethane. The filtrate was concentrated at 30 C. at 250 mbar, silica added and the residue was purified by chromatography eluting with 0-10% ethyl acetate/hexane. Fractions containing product were combined to give 2-methoxy-6-(trifluoromethyl)pyridine (6.49 g, 36.6 mmol, 59.8% yield).

(119) 1H NMR (CDCl.sub.3): 7.69 (t, J=8.1 Hz, 1H) 7.25 (d, J=7.5 Hz, 1H) 6.91 (d, J=8.6 Hz, 1H) 3.98 (s, 3H);

[2-methoxy-6-(trifluoromethyl)-3-pyridyl]boronic acid

(120) To a solution of 2-methoxy-6-(trifluoromethyl)pyridine (1.0 g, 5.6 mmol) and in diethyl ether (1.2 mL/mmol, 6.8 mL) at 78 C under nitrogen was added nBuLi (2.5 mol/L) in hexanes (4.7 g, 17 mmol, 6.8 mL) over 5 min and allowed to warm up to room temperature over 30 minutes. Boric acid triisopropyl ester (2.1 g, 11 mmol, 2.6 mL) in diethyl ether (1.2 mL/mmol, 6.8 mL) was cooled to 78 C and [2-methoxy-6-(trifluoromethyl)-3-pyridyl]lithium was added to this solution over 15 minutes and then warmed up to room temperature over 30 mins.

(121) Hydrogen chloride (aqueous 25%) (10 mL, 10 mmol) was added and the reaction mixture diluted with water and extracted twice with dichloromethane, passed through a phase separator and reduced under vacuum to give a yellow oil which solidified overnight.

(122) The reaction mixture was adsorbed onto silica and purified by chromatography on silica, eluting with 0-25% ethyl acetate/hexane. Fractions containing product were combined to give [2-methoxy-6-(trifluoromethyl)-3-pyridyl]boronic acid as a yellow solid (707 mg, 3.20 mmol, 59% yield).

(123) 1H NMR (11vu941h1, CDCl.sub.3): 8.29 (d, J=7.5 Hz, 1H) 7.34 (d, J=7.5 Hz, 1H) 5.92 (s, 2H) 4.10 (s, 3H);

4-methoxy-5-[2-methoxy-6-(trifluoromethyl)-3-pyridyl]-2-methyl-pyridazin-3-one

(124) To a mixture of 5-chloro-4-methoxy-2-methyl-pyridazin-3-one (400 mg, 2.29 mmol), prepared as described in Example 2, [2-methoxy-6-(trifluoromethyl)-3-pyridyl]boronic acid (0.71 g, 3.20 mmol) sPhos (0.19 g, 0.46 mmol) tris(dibenzylidineacetonyl)bispalladium (0.11 g, 0.11 mmol), potassium phosphate (1.00 g, 4.58 mmol, 0.39 mL) and the reaction mixture diluted with tert-butanol (1.6 mL/mmol, 2.88 g, 38.5 mmol, 3.67 mL). The reaction mixture was heated to 80 C for 50 min. The reaction mixture was diluted with brine and extracted with ethyl acetate (3). The orange solution was passed through a phase separator, silica added and reduced under vacuum. This was then purified by chromatography, eluting with 0-50% ethyl acetate/hexane. Fractions containing product were combined to give 4-methoxy-5-[2-methoxy-6-(trifluoromethyl)-3-pyridyl]-2-methyl-pyridazin-3-one (545 mg, 0.54 g, 1.73 mmol, 75.46% yield)

5-[2-hydroxy-6-(trifluoromethyl)-3-pyridyl]-4-methoxy-2-methyl-pyridazin-3-one

(125) To 4 microwave vials was added in each 1 g of 4-methoxy-5-[2-methoxy-6-(trifluoromethyl)-3-pyridyl]-2-methyl-pyridazin-3-one (4.0 g, 13 mmol) followed by 15 ml of hydrogen bromide (48% aqueous solution) (60 ml) and heated sequentially at 40 C in the microwave for 45 minutes. The reaction mixtures were combined and ethyl acetate was added followed by brine and then extracted with ethyl acetate (310 ml), the combined organics passed through a phase separator and reduced under vacuum to give a white solid. This was then purified by chromatography, eluting with 0-50% ethyl acetate/hexane.

(126) Fractions containing product were combined to give 5-[2-hydroxy-6-(trifluoromethyl)-3-pyridyl]-4-methoxy-2-methyl-pyridazin-3-one as a pink solid (1.6 g, 5.3 mmol, 42% yield)

(127) 1H NMR (11vz747h1, CDCl.sub.3): 7.83 (s, 1H) 7.75 (d, J=7.6 Hz, 1H) 6.96 (d, J=7.4 Hz, 1H) 4.18 (s, 3H) 3.82 (s, 3H);

4-methoxy-2-methyl-5-[1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]pyridazin-3-one

(128) To a solution of 5-[2-hydroxy-6-(trifluoromethyl)-3-pyridyl]-4-methoxy-2-methyl-pyridazin-3-one (150 mg, 0.49797 mmol) in 1,2-dimethoxyethane (12 ml/mmol, 5.98 mL) was added dipotassium carbonic acid (0.21 g, 1.49 mmol) followed by iodomethane (0.64 g, 4.48 mmol, 0.28 ml) and the reaction mixture heated to reflux (75 C) for 30 min. The reaction mixture was cooled to room temperature and the inorganic solids were filtered and washed with ethyl acetate and the solvent; silica was added and the reaction mixture concentrated under vacuum and purified by chromatography, eluting with 0-35-50% ethyl acetate/hexane.

(129) Fractions containing product were combined to give 4-methoxy-2-methyl-5-[1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]pyridazin-3-one as a white solid (88 mg, 0.28 mmol, 56.06% Yield)

(130) 1H NMR (12wk938h1, CDCl.sub.3): 7.82 (s, 1H) 7.55 (d, J=7.5 Hz, 1H) 6.78 (d, J=7.0 Hz, 1H) 4.16 (s, 3H) 3.80 (s, 3H) 3.70 (d, J=1.1 Hz, 3H)

4-hydroxy-2-methyl-5-[1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]pyridazin-3-one

(131) A solution of 4-methoxy-2-methyl-5-[1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]pyridazin-3-one (88 mg, 0.2792 mmol) in morpholine (1 ml, 11.4 mmol) was heated to 100 C for 1.5 h. The reaction mixture was reduced under vacuum, diluted with ethyl acetate, washed with 1M HCl 3 times, reduced under vacuum and triturated with TBME to give 4-hydroxy-2-methyl-5-[1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridyl]pyridazin-3-one as a white solid (48 mg, 0.16 mmol, 57.08% yield)

(132) TABLE-US-00001 TABLE C1 Examples of herbicidal compounds of the present invention. 0 Compound R.sup.1 R.sup.2 R.sup.3 NMR 1.001 CH.sub.2OMe H 2.24 (3H, s), 3.22 (3H, s), 3.31- 3.52 (2H, m), 3.55 (3H, s), 4.61 (2H, t, J = 10.0), 5.54 (2H, s), 7.52 (1H, d, J = 8.2), 7.70 (1H, s), 8.10 (1H, d, J = 8.2) 1.002 p-methoxybenzyl- H 2.21 (s, 3H), 3.21 (s, 3H), 3.38 (br. s., 2H), 3.80 (s, 3H), 4.60 (t, J = 10.00 Hz, 2H), 5.33 (s, 2H), 6.87-6.92 (m, 2H), 7.43-7.49 (m, 3H), 7.64 (s, 1H), 8.06 (d, J = 8.19 Hz, 1H) 1.003 sec-butyl H 1.004 H 1.51-1.66 (3H, m), 1.71-1.88 (3H, m), 2.23 (3H, s), 3.21 (3H, s), 3.75-3.86 (2H, br s), 4.20 (1H, dd, J = 11.6, 4.0), 4.60 (2H, t, J = 9.9), 6.09 (1H, dd, J = 10.7, 2.2), 7.49 (1H, d, J = 8.1), 7.74 (1H, s), 8.08 (1H, d, J = 8.1). 1.005 CHF.sub.2 H 2.21 (3H, s), 3.20 (3H, s), 3.40 (2H, br s), 4.61 (2H, t, J = 10.0), 6.98 (1H, t, J = 60), 7.49 (1H, d, J = 8.1), 8.08 (1H, s), 8.21 (1H, s, J = 8.1). 1.006 CHF.sub.2 H 6.96 (1H, t, J = 60), 7.60 (1H, d, J = 8.1), 7.92 (1H, d, J = 8.1), 8.07 (1H, s), 8.19 (1H, s). 1.007 Cyclopentyl H 8.09 (1H, d), 7.69 (1H, s), 7.51 (1H, d), 5.46-5.39 (1H, m), 4.60 (2H, t), 3.41 (2H, br s), 3.21 (3H, s), 2.23 (3H, s), 2.18-2.09 (2H, m), 2.04-1.88 (4H, m), 1.78-1.69 (2H, m) 1.008 Cyclopropyl H 1.00-1.15 (2H, m), 1.20-1.32 (2H, m), 2.23 (3H, s), 3.21 (3H, s), 3.38 (2H, br s), 4.18 (1H, dt, J = 7.7, 3.7), 4.60 (2H, t, J = 10.0), 7.49 (1H, d, J = 8.2), 7.60 (1H, s), 8.08 (1H, d, J = 8.1) 1.009 Et 0 H 1.47 (3H, t, J = 7.2), 3.27 (3H, s), 3.47 (2H, t, J = 10.1), 4.30 (2H, q, J7.2), 4.63 (2H, t, J = 10.1), 7.68 (1H, d, J = 8.2), 7.74 (1H, s), 8.16 (1H, d, J = 8.2). 1.010 Et H 7.71 (1H, s), 7.56 (1H, d), 7.30 (1H, d), 4.30 (2H, q), 1.46 (3H, t) 1.011 Et H 7.63 (1H, s), 7.43 (1H, d), 7.34-7.30 (1H, m), 4.30 (2H, br d), 1.47 (3H, br t) 1.012 i-Pr H 1.45 (6H, d, J = 6.4), 2.24 (3H, s), 3.22 (3H, s), 3.39 (2H, br s), 4.61 (2H, t, J = 10.2), 5.22-5.38 (1H, m), 7.52 (1H, d, J = 8.1), 7.70 (1H, s), 8.08 (1H, d, J = 8.1). 1.013 i-Pr H 8.47 (1H, d), 7.99 (1H, dd), 7.75 (1H, s), 7.55 (1H, d), 5.27 (1H, septet), 3.04 (3H, s), 1.46 (6H, d) 1.014 i-Pr H 1.45 (6H, d, J = 7.0), 3.27 (3H, s), 3.47 (2H, t, J = 10.3), 4.63 (2H, t, J = 10.2), 5.30 (1H, m), 7.69 (1H, d, J = 8.1), 7.78 (1H, s), 8.16 (1H, d, J = 8.1). 1.015 i-Pr H 7.75 (1H, s), 7.56 (1H, d), 7.31 (1H, d), 5.28 (1H, septet), 1.44 (6H, d) 1.016 i-Pr H 7.67 (1H, s), 7.45- 7.43 (2H, 2 app s), 7.32 (1H, dd), 5.29 (1H, septet), 1.45 (6H, d) 1.017 Me H 7.82 (1H, s), 7.74 (1H, d), 6.61 (1H, d), 3.79 (3H, s) 1.018 Me H 8.08 (1H, d), 7.64 (1H, s), 7.50 (1H, d), 4.61 (2H, t), 3.91 (3H, s), 3.40 (2H, br s), 3.22 (3H, s), 2.24 (3H, s) 1.019 Me 0 H 3.60 (s, 3H), 6.37- 6.40 (m, 1H), 7.51- 7.52 (m, 1H), 7.77- 7.78 (m, 1H), 7.86 (s, 1H), 11.87 (br s, 1H). 1.020 Me H 3.86 (s, 3H), 3.98 (s, 3H), 6.99-7.03 (m, 1H), 7.80-7.82 (m, 1H), 7.91 (s, 1H), 8.22-8.34 (m, 1H) 1.021 Me H 1.022 Me H 7.82 (2H, m), 7.68- 7.75 (1H, m), 7.52- 7.60 (2H, m), 3.89 (3H, s) 1.023 Me H 3.66 (3H, s); 6.66- 6.70 (1H, dd); 6.83 (1H, d); 7.64- 7.66 (1H, d); 7.78- 7.82 (2H, d); 7.85 (1H, s); 7.91- 7.93 (2H, d). 1.024 Me H 9.22 (1H, s), 8.80 (2H, s), 7.91 (2H, m), 6.83 (1H, d), 3.82 (3H, s) 1.025 Me H 7.90 (1H, s), 7.25 (1H, s), 6.99 (1H, s), 3.87 (3H, s), 3.78 (4H, m), 2.86 (4H, m) 1.026 Me H 7.87 (1H, s), 7.22 (1H, d), 6.45 (1H, d), 3.86 (3H, s), 3.79 (4H, m), 3.17 (4H, br m) 1.027 Me H 2.40 (3H, s); 3.64 (3H, s); 6.14- 6.20 (2H, m); 7.32- 7.34 (1H, d); 7.76 (1H, s). 1.028 Me H 8.48 (1H, br d), 8.00 (1H, dd), 7.69 (1H, s), 7.54 (1H, d), 3.90 (3H, s), 3.03 (3H, s) 1.029 Me 0 H 8.47 (1H, d), 7.86 (1H, dd), 7.68 (1H, s), 7.48 (1H, d), 3.90 (3H, s), 2.67 (3H, s) 1.030 Me H 3.09 ppm (3H, s); 3.90 ppm (3H, s); 5.11 ppm (2H, s); 5.47 ppm (2H, s); 7.53 ppm (1H, d); 7.71 ppm (1H, s); 7.93 ppm (1H, d) 1.031 Me H 2.24 (3H, s); 2.62 ppm (2H, m); 2.78 ppm (3H, s); 3.52 ppm (2H, m); 3.90 ppm (3H, s); 4.20 ppm (2H, m); 4.31 ppm (2H, m); 7.19 ppm (1H, s); 7.59 ppm (1H, s) 1.032 Me H 3.27 (3H, s), 3.47 (2H, t, J = 10.2), 3.90 (3H, s), 4.63 (2H, t, J = 10.2), 7.68 (1H, d, J = 8.1), 7.72 (1H, s), 8.16 (1H, d, J = 8.1). 1.033 Me H 8.07 (1H, s), 7.91 (1H, d),7.62 (1H, s), 7.54 (1H, d), 3.90 (3H, s) 1.034 Me H 3.35 ppm (3H, s); 3.49 ppm (3H, s); 3.87 ppm (2H, t); 3.90 ppm (3H, s); 4.47 ppm (2H, t); 7.35 ppm (1H, d); 7.71 ppm (1H, s); 8.00 ppm (1H, d) 1.035 Me H 2.70 ppm (3H, s); 3.27 ppm (3H, s); 3.92 ppm (3H, s); 7.63 ppm (1H, s); 7.70 ppm (1H, d); 7.87 ppm (1H, d) 1.036 Me H 8.18 (1H, dd), 7.72 (1H, td), 7.70 (1H, s), 7.61 (1H, td), 7.33 (1H, dd), 3.89 (3H, s), 2.66 (3H, s) 1.037 Me H 7.85 (1H, s), 7.76 (1H, d), 7.42-7.40 (2H, m), 7.31 (1H, m), 7.22-7.20 (1H, m), 6.72 (1H, d), 3.78 (3H, s) 1.038 Me H 7.88 (1H, s), 7.75 (1H, d), 7.34-7.31 (1H, m), 7.25-7.24 (1H, m), 7.12 (1H, s), 7.09 (1H, d), 6.74 (1H, d), 3.81 (3H, s), 2.40 (3H, s) 1.039 Me 0 H 9.24 (1H, dd), 8.64 (1H, s), 8.61 (1H, dd), 7.84 (1H, dd), 7.77 (1H, s), 3.85 (3H, s) 1.040 Me H 7.81 (1H, d), 7.75 (1H, d), 7.63 (1H, s), 4.62 (2H, s), 3.90 (3H, s), 2.99 (3H, s), 2.90 (3H, s) 1.041 Me H 8.10 (1H, dd), 7.74 (1H, s), 7.70 (1H, td), 7.62 (1H, td), 7.35 (1H, dd), 3.90 (3H, s), 2.89-2.80 (1H, m), 2.77-2.68 (1H, m), 1.20 (3H, t) 1.042 Me H 8.16 (1H, dd), 7.74 (1H, td), 7.72 (1H, s), 7.67 (1H, td), 7.37 (1H, dd), 3.88 (3H, s), 3.01 (2H, q), 1.21 (3H, t) 1.043 Me H 8.06 (1H, dd), 7.76 (1H, s), 7.68 (1H, td), 7.61 (1H, td), 7.36 (1H, dd), 3.90 (3H, s), 2.72 (1H, septet), 1.10 (3H, d), 1.08 (3H, d) 1.044 Me H 8.14 (1H, dd), 7.74- 7.71 (1H, m), 7.73 (1H, s), 7.65 (1H, td), 7.37 (1H, dd), 3.88 (3H, s), 3.05 (1H, septet), 1.20 (6H, br d) 1.045 Me H 2.37 ppm (3H, d); 3.87 ppm (3H, s); 7.29 ppm (2H, m); 7.79 ppm (1H, d) 1.046 Me H 8.21 (1H, dd), 7.77- 7.66 (2H, m), 7.71 (1H, s), 7.37 (1H, dd), 3.89 (3H, s), 2.99 (3H, s) 1.047 Me H 8.12 (1H, dd), 7.72 (1H, s), 7.69 (1H, td), 7.60 (1H, td), 7.33 (1H, dd), 3.89 (3H, s), 2.74-2.70 (2H, m), 1.75-1.52 (2H, m), 1.44-1.24 (2H, m), 0.85 (3H, t) 1.048 Me H 1.61 ppm (1H, m); 1.90 ppm (2H, m); 1.98 ppm (1H, m); 3.35 ppm (3H, s); 3.67 ppm (2H, m); 3.77 ppm (1H, m); 3.84 ppm (1H, m); 3.90 ppm (3H, s); 4.12 ppm (1H, m); 5.26 ppm (2H, m); 7.55 ppm (1H, d); 7.71 ppm (1H, s); 8.17 ppm (1H, d) 1.049 Me 0 H 3.26 ppm (3H, s); 3.91 ppm (3H, s); 4.08 ppm (2H, q); 5.42 ppm (2H, s); 7.61 ppm (1H, d); 7.72 ppm (1H, s): 8.19 ppm (1H, d) 1.050 Me H 3.34 ppm (3H, s); 3.89 ppm (3H, s); 7.52 ppm (1H, d); 7.70 ppm (1H, s); 8.19 ppm (1H, d) 1.051 Me H 8.16 (1H, dd), 7.75- 7.72 (1H, m), 7.72 (1H, s), 7.66 (1H, td), 7.36 (1H, dd), 3.88 (3H, s), 2.99 (2H, app t), 1.59 (2H, br d), 1.37-1.28 (2H, m), 0.85 (3H, t) 1.052 Me H 7.86 (1H, s), 7.77 (1H, d), 7.64-7.60 (1H, m), 7.57-7.52 (1H, m), 7.47 (1H, d), 7.28 (1H, br d), 6.57 (1H, d), 3.85 (3H, s) 1.053 Me H 7.82 (1H, s), 7.76 (1H, d), 7.30-7.19 (3H, m), 7.08 (1H, d), 6.73 (1H, d), 3.77 (3H, m), 2.12 (3H, s) 1.054 Me H 7.85 (1H, s), 7.73 (1H, d), 7.42-7.40 (3H, m), 7.28-7.26 (2H, m), 6.72 (1H, d), 3.78 (3H, s) 1.055 Me H 8.26-8.24 (1H, m), 7.78-7.76 (2H, m), 7.68 (1H, s), 7.42- 7.40 (1H, m), 3.90 (3H, s) 1.056 Me H 8.27 (1H, d), 7.91 (1H, td), 7.77 (1H, td), 7.65 (1H, s), 7.51 (1H, dd), 3.89 (3H, s) 1.057 Me H 7.90 (1H, dd), 7.67 (1H, s), 7.36-7.27 (2H, m), 3.89 (3H, s), 2.64 (3H, s) 1.058 Me H 7.93 (1H, dd), 7.69 (1H, s), 7.46-7.42 (1H, m), 7.37 (1H, dd), 3.88 (3H, s), 3.00 (3H, s) 1.059 Me 0 H 8.14 (1H, d), 7.66 (1H, s), 7.57 (1H, dd), 7.27 (1H, d), 3.87 (3H, s), 2.66 (3H, s) 1.060 Me H 3.64 (3H, s); 3.99 (3H, s); 6.14- 6.16 (1H, d); 7.68- 7.70 (1H, d); 7.89 (1H, s). 1.061 Me H 8.20 (1H, d), 7.70 (1H, dd), 7.68 (1H, s), 7.31 (1H, d), 3.88 (3H, s), 3.00 (3H, s) 1.062 Me H 2.02 (3H, s); 3.72 (3H, s); 6.22- 6.26 (1H, t); 7.39- 7.41 (2H, d); 7.84 (1H, s); 11.7- 11.9 (1H br s). 1.063 Me H 3.88 ppm (3H, s); 4.02 ppm (3H, d); 7.19 ppm (1H, dd); 7.28 ppm (1H, dd); 7.81 ppm (1H, d) 1.064 Me H 2.92 ppm (6H, 2s); 3.88 ppm (3H, s); 7.15 ppm (1H, dd); 7.26 ppm (1H, dd); 7.80 ppm (1H, d) 1.065 Me H 2.18 (3H, s); 3.70 (3H, s); 6.18- 6.20 (1H, dd); 6.30 (1H, s); 7.40- 7.42 (1H, d); 7.82 (1H, s); 11.7- 11.9 (1H br s). 1.066 Me H 3.70 (3H, s); 6.17- 6.19 (1H, d); 7.70- 7.72 (1H, d); 7.87 (1H, s). 1.067 Me H 7.74 (1H, d), 7.66 (1H, s), 7.62 (1H, d), 3.90 (3H, s), 2.58 (3H, s) 1.068 Me H 7.83 (1H, d), 7.67 (1H, s), 7.59 (1H, d), 5.90 (1H, dq), 3.90 (3H, s), 2.59 (3H, s), 1.76 (3H, dd) 1.069 Me 0 H 3.72 (3H, s); 6.70-6.72 (1H, d); 7.30-7.32 (1H, d); 7.53-7.57 (1H, t); 7.70-7.72 (1H, d); 7.76-7.80 (1H, t); 7.92 (1H, s); 8.21-8.23 (1H, d). 1.070 Me H 3.79 (3H, s); 3.84 (3H, s); 6.39- 6.43 (1H, t); 6.98- 7.00 (1H, d); 7.08- 7.10 (1H, d); 7.78 (1H, s). 1.071 Me H 8.10 (1H, s), 7.94 (1H, dd), 7.60 (1H, s), 7.54 (1H, d), 3.89 (3H, s) 1.072 Me H 7.88 (1H, d), 7.83 (1H, s), 7.73 (1H, d), 4.70 (2H, s), 3.90 (3H, s), 3.60- 3.58 (2H, m), 3.45- 3.43 (2H, m), 3.30 (3H, s) 1.073 Me H 7.88 (1H, d), 7.81 (1H, s), 7.74 (1H, d), 4.57 (2H, s), 3.90 (3H, s), 3.35 (3H, s) 1.074 Me H 8.42 (1H, d), 8.21 (1H, s), 8.19 (1H, s), 7.73 (1H, dd), 7.53 (1H, dd), 7.38 (1H, dd), 7.07 (1H, dd), 3.85 (3H, s) 1.075 Me H 7.99 (1H, s), 7.87 (1H, d), 7.33 (1H, d), 3.87 (3H, s), 3.73 (4H, m), 3.26 (4H, m) 1.076 Me H 7.79 (1H, br s), 7.73 (1H, s), 7.63 (1H, dd), 7.54 (1H, d), 3.89 (3H, s) 1.077 Me H 7.71 (1H, d), 7.66 (1H, s), 7.47 (1H, d), 7.39 (1H, d), 3.67 (3H, s) 1.078 Me H 7.83 (1H, s), 7.75 (1H, d), 6.94 (1H, br m), 6.61 (1H, dd), 3.79 (3H, s) 1.079 Me 00 H 8.66 (1H, d), 8.28 (1H, dd), 7.72 (1H, s), 7.71 (1H, d), 3.90 (3H, s), 3.18 (3H, s) 1.080 Me 01 H 1.081 Me 02 H 8.35 (1H, d), 7.86 (1H, dd), 7.68 (1H, s), 7.24 (1H, d), 3.88 (3H, s), 3.00 (3H, s) 1.082 Me 03 H 7.69 (1H, s), 7.33- 7.27 (1H, m), 7.23- 7.19 (1H, m), 7.06 (1H, dd), 3.73 (3H, s), 2.06 (3H, d) 1.083 Me 04 H 7.69 (1H, s), 7.33- 7.27 (1H, m), 7.23- 7.19 (1H, m), 7.06 (1H, dd), 3.73 (3H, s), 2.06 (3H, d) 1.084 Me 05 H 7.82 (1H, br s), 7.73 (1H, dd), 7.71 (1H, s), 7.42 (1H, d), 3.73 (3H, s), 2.21 (3H, s) 1.085 Me 06 H 7.74 (1H, d), 7.40 (1H, app t), 6.92 (1H, dd), 6.86 (1H, dd), 3.80 (3H, s), 3.70 (3H, s) 1.086 Me 07 H 7.62 (1H, s), 7.51 (1H, dd), 7.26-7.19 (2H, m), 3.63 (3H, s) 1.087 Me 08 H 8.89 (1H, d), 8.63 (1H, dd), 7.77 (1H, d), 3.88 (3H, s), 3.04 (3H, s) 1.088 Me 09 H 8.45 (1H, s), 7.56 (1H, s), 3.90 (3H, s), 2.98 (3H, s) 1.089 Me 0 H 8.00 (1H, s), 7.77 (1H, s), 7.74 (1H, s), 3.72 (3H, s) 1.090 Me H 7.66 (1H, s), 7.42 (1H, d), 6.99-6.94 (2H, m), 3.73 (3H, s), 3.69 (3H, s) 1.091 Me H 7.75 (1H, s), 7.74 (1H, d), 7.44 (1H, d), 3.72 (3H, s) 1.092 Me H 7.70 (1H, s), 7.66 (1H, dd), 7.29 (1H, dd), 3.69 (3H, s) 1.093 Me H 7.66 (1H, s), 7.24 (1H, dd), 7.16 (1H, dd), 7.08 (1H, td), 3.73 (3H, s), 2.16 (3H, s) 1.094 Me H 7.69 (1H, s), 7.33 (1H, dd), 7.15 (1H, td), 7.08 (1H, dd), 3.73 (3H, s), 2.13 (3H, s) 1.095 Me H 8.00 (2H, d), 7.77 (1H, s), 7.61-7.46 (5H, m), 3.79 (3H, s) 1.096 Me H 7.91-7.86 (3H, m), 7.60-7.55 (1H, m), 3.73 (3H, s) 1.097 Me H 7.68-7.17 (4H, m), 3.63 (6H, m) 1.098 Me H 7.75-7.66 (4H, m), 3.74 (3H, s), 2.50 (3H, s) 1.099 Me 0 H 7.68 (1H, s), 7.57- 7.54 (1H, m), 7.48- 7.45 (2H, m), 3.68 (3H, s) 1.100 Me H 7.55 (1H, s), 7.40 (1H, d), 7.15 (1H, d), 7.11-7.08 (1H, m), 3.743 (3H, s) 1.101 Me H 7.59 (1H, s), 7.25 (1H, d), 7.07-7.03 (2H, m), 3.74 (3H, s), 2.25 (3H, s) 1.102 Me H 7.68 (1H, s), 7.56 (1H, d), 7.30 (1H, d), 3.88 (3H, s) 1.103 Me H 7.58 (1H, s), 7.18 (1H, d), 6.91 (1H, d), 6.77 (1H, dd), 3.72 (3H, s), 3.71 (3H, s) 1.104 Me H 7.70 (1H, s), 7.61 (1H, d), 7.35 (1H, d), 7.24 (1H, dd), 3.93 (3H, s), 3.88 (3H, s) 1.105 Me H 8.09 (1H, d), 8.00 (1H, dd), 7.79 (1H, d), 7.75 (1H, s), 3.77 (3H, s), 3.26 (3H, s) 1.106 Me H 8.20 (1H, dd), 8.01 (1H, dd), 7.60 (1H, s), 7.55 (1H, app t), 3.90 (3H, s), 2.98 (3H, s) 1.107 Me H 7.97 (1H, d), 7.71 (1H, s), 7.32 (1H, d), 4.35 (2H, q), 3.90 (3H, s), 3.30 (3H, s), 1.53 (3H, t) 1.108 Me H 7.88 (1H, d), 7.72 (1H, s), 7.13 (1H, d), 3.84 (3H, s), 3.35 (3H, s) 1.109 Me 0 H 8.11 (1H, d), 7.70 (1H, dd), 7.69 (1H, s), 7.41 (1H, d), 3.88 (3H, s) 1.110 Me H 8.38 (1H, s), 7.98 (1H, d), 7.72 (1H, s), 7.63 (1H, d), 3.89 (3H, s) 1.111 Me H 8.12 (1H, dd), 7.76- 7.71 (1H, m), 7.73 (1H, s), 7.64-7.60 (1H, m), 7.47 (1H, d), 3.88 (3H, s) 1.112 Me H 7.62 (1H, s), 7.51 (1H, dd), 7.39-7.32 (2H, m), 3.87 (3H, s) 1.113 Me H 7.79 (1H, d), 7.62 (1H, dd), 7.61 (1H, s), 7.32 (1H, d), 3.89 (3H, s) 1.114 Me H 7.75 (1H, s), 7.53- 7.51 (1H, m), 7.41- 7.36 (3H, m), 3.89 (3H, s) 1.115 Me H 7.62 (1H, s), 7.30 (1H, d), 7.28 (1H, d), 7.14 (1H, d), 3.89 (3H, s), 3.88 (3H, s) 1.116 Me H 7.80 (1H, d), 7.66- 7.63 (2H, overlapping s and m), 7.59-7.55 (1H, m), 7.37 (1H, d), 3.89 (3H, s) 1.117 Me H 1.118 Me H 7.60 (1H, s), 7.43 (1H, d), 7.34-7.30 (1H, m), 3.90 (3H, s) 1.119 Me 0 H 8.47 (1H, s), 8.27 (1H, d), , 7.71 (1H, d), 7.67 (1H, s), 3.68 (3H, s), 3.32 (3H, s), 3.15 (3H, s) 1.120 methylcyclopropyl H 0.46-0.53 (2H, m), 0.57-0.67 (2H, m), 1.37-1.48 (1H, m), 2.25 (3H, s), 3.22 (3H, s), 3.39 (1H, br s), 4.11 (2H, d, J = 7.2), 4.61 (2H, t, J = 10.1), 7.53 (1H, d, J = 8.1), 7.66 (1H, s), 8.09 (1H, d, J = 8.1) 1.121 methylcyclopropyl H 8.49 (1H, d), 7.99 (1H, dd), 7.71 (1H, s), 7.57 (1H, d), 4.11 (2H, br m), 3.04 (3H, s), 1.42 (1H, m), 0.64-0.59 (2H, m), 0.50-0.47 (2H, m) 1.122 methylcyclopropyl H 8.48 (1H, s), 7.87 (1H, d), 7.70 (1H, m), 7.51 (1H, d), 4.11 (2H, m), 2.70 (3H, m), 1.42 (1H, m), 0.62 (2H, m), 0.50 (2H, m) 1.123 n-Bu H 7.70 (1H, s), 7.56 (1H, d), 7.31 (1H, d), 4.23 (2H, dd), 1.90-1.82 (2H, m), 1.47-1.38 (2H, m), 0.99 (3H, t) 1.124 n-Bu H 7.62 (1H, br s), 7.48-7.28 (3H, br m), 4.24 (2H, br m), 1.87 (2H, br m), 1.42 (2H, br m), 0.99 (3H, br m) 1.125 n-Pr H 1.02 (3H, t, J = 7.5), 1.84-1.97 (2H, m), 3.27 (3H, s), 3.47 (2H, t, J = 9.9), 4.16- 4.25 (2H, m), 4.63 (2H, t, J = 10.2), 7.69 (1H, d, J = 8.1), 7.74 (1H, s), 8.16 (1H, d, J = 8.1). 1.126 n-Pr H 7.79 (1H, br d), 7.74 (1H, s), 7.63 (1H, dd), 7.55 (1H, d), 4.20 (2H, m), 1.96- 1.87 (2H, m), 1.02 (3H, t) 1.127 n-Pr H 1.128 n-Pr H 7.70 (1H, s), 7.56 (1H, d), 7.31 (1H, d), 4.19 (2H, dd), 1.95-1.86 (2H, m), 1.01 (3H, t) 1.129 n-Pr 0 H 7.70-7.00 (4H, br m), 4.20 (2H, br m), 1.90 (2H, br m), 1.00 (3H, br m) 1.130 Ph H 2.31 (3H, s), 3.23 (3H, s), 3.41 (2H, d, J = 4.6), 4.62 (2H, t, J = 10.0), 7.43-7.49 (1H, m), 7.51-7.60 (3H, m), 7.71-7.76 (2H, m), 7.81 (1H, s), 8.12 (1H, d, J = 8.2). 1.131 t-Bu H 1.73 (9H, s), 2.25 (3H, s), 3.22 (3H, s), 3.39 (2H, br s), 4.61 (2H, t, J = 9.9), 7.51 (1H, d, J = 8.1), 7.62 (1H, s), 8.08 (1H, d, J = 8.1). 1.132 t-Bu H 7.67 (1H, s), 7.55 (1H, d), 7.31 (1H, d), 1.71 (9H, s) 1.133 t-Bu H 7.58 (1H, s), 7.44- 7.42 (2H, 2 app s), 7.33-7.29 (1H, m), 1.73 (9H, s) 1.134 Me H 2.88 (6H, s) 3.87 (3H, s) 7.22 (1H, d, J = 7.5 Hz) 7.77 (1H, d, J = 7.0 Hz) 7.82 (1H, s) 1.135 Me H 1.37-1.48 (3H, m) 3.66 (2H, q, J = 7.5 Hz) 3.88 (3H, s) 7.91 (1H, s) 7.98 (1H, d, J = 8.1 Hz) 8.13 (1H, d, J = 8.1 Hz) 1.136 cPr H 1.06 (dd, J = 7.52, 1.61 Hz, 2H), 1.22- 1.31 (m, 2H), 2.99 (s, 3H), 4.15 (tt, J = 7.67, 3.94 Hz, 1H), 7.36 (dd, J = 7.52, 1.21 Hz, 1H), 7.64-7.77 (m, 3H), 8.20 (dd, J = 7.86, 1.28 Hz, 1H) 1.137 Me H 1.138 Me H 8.02 (br. s., 1H) 7.77-7.93 (m, 3H) 7.63-7.76 (m, 2H) 6.44 (t, J = 7.0 Hz, 1H) 3.60 (s, 3H); 1.139 Me 0 H 8.21 (1H, d), 7.73 (1H, dd), 7.70 (1H, s), 7.32 (1H, d), 6.80 (1H, dd), 5.95 (1H, d), 5.50 (1H, d), 3.88 (3H, s), 2.99 (3H, s) 1.140 Me H 8.26 (1H, d), 7.79 (1H, dd), 7.70 (1H, s), 7.33 (1H, d), 5.55 (1H, br m), 5.29 (1H, br m), 3.88 (3H, s), 2.99 (3H, s), 2.22 (3H, br m) 1.141 Me H 8.51 (1H, d), 8.01 (1H, dd), 7.68 (1H, s), 7.53 (1H, d), 3.89 (3H, s), 3.02 (3H, s) 1.143 Me H 7.86 (br. s., 1H) 7.65 (d, J = 5.9 Hz, 1H) 7.58 (br. s., 1H) 7.49 (br. s., 1H) 7.40 (br. s., 1H) 6.40 (t, J = 7.0 Hz, 1H) 3.58 (br. s., 3H); 1.144 CH.sub.3OCH.sub.2 H 8.21 (1H, dd), 7.77- 7.74 (1H, m), 7.75 (1H, s), 7.71-7.67 (1H, m), 7.38 (1H, dd), 5.57-5.47 (2H, br m), 3.53 (3H, s), 3.00 (3H, s) 1.145 CH.sub.3OCH.sub.2 H 8.19 (1H, dd), 7.75 (1H, s), 7.72 (1H, dd), 7.62 (1H, td), 7.34 (1H, dd), 5.55- 5.50 (2H, m), 3.54 (3H, s), 2.69 (3H, s) 1.146 CH.sub.3OCH.sub.2 H 8.47 (1H, d), 7.87 (1H, dd), 7.74 (1H, s), 7.49 (1H, d), 5.54 (1H, d), 5.51 (1H, d), 3.55 (3H, s), 2.69 (3H, s) 1.147 Me H 8.39-8.43 (m, 1H) 8.30-8.36 (m, 1H) 7.97-8.02 (m, 1H) 7.93 (s, 1 H) 7.81-7.89 (m, 3H) 6.53 (t, J = 7.0 Hz, 1H) 3.67 (s, 3H); 1.148 Me H 8.11 (s, 1H) 7.90 (dd, J = 5.9, 1.1 Hz, 1H) 7.49 (m, J = 5.9 Hz, 2H) 7.17-7.24 (m, 2H) 6.49 (t, J = 7.0 Hz, 1H) 3.84 (s, 2H); 1.149 Me H 3.90 (2H, s) 7.73 (1H, d, J = 1.074 Hz) 8.02 (1H, dd, J = 2.149, 1.074 Hz) 1.150 Me 0 H 3.88 (2H, s) 4.07 (2H, s) 6.93 (1H, d, J = 5.37 Hz) 7.73 (1H, s) 8.14 (1H, d, J = 5.37 Hz) 8.15-8.16 (1H, m) 1.151 Me H 8.26 (s, 1H), 7.82 (d, 1H), 7.71 (s, 1H), 3.91 (s, 3H), 2.87 (d, 3H) 1.152 Me H 7.89 (s, 2H), 7.79- 7.81 (m, 5H), 6.51- 6.54 (t, 1H), 3.66 (s, 3H); 1.153 Me H 3.85 (3H, s), 3.97 (3H, s), 4.05 (s, 3H), 6.40-6.44 (1H, d), 7.75-7.77 (1H, d), 7.93 (1H, s) 1.154 Me H 8.20 (s, 1H), 8.18 (d, 1H), 7.71 (s, 1H), 7.56 (d, 1H), 3.90 (s, 3H), 2.90 (s, 3H) 1.156 Me H 8.09 (br s, 1H), 7.88- 7.90 (d, 1H), 7.50-7.51 (d, 1H), 7.41-7.45 (t, 1H), 6.94-7.03 (m, 2H), 6.48-6.52 (t, 1H), 3.84 (s, 3H), 3.83 (br s, 3H); 1.157 Me Me 8.08-8.10 (d, 1H), 7.38-7.40 (d, 1H), 4.58-4.63 (t, 2H), 3.86 (s, 3H), 3.40 (br s, 2H), 3.23 (s, 3H), 2.13 (s, 3H), 2.02 (s, 3H) 1.157 Me H 9.18 (d, 1H), 8.35 (s, 1H), 7.98 (dd, 1H), 7.69 (s, 1H), 3.90 (s, 3H) 1.158 cPr H 3.30 (s, 6H), 3.47 (t, J = 10.27 Hz, 4H), 4.64 (t, J = 10.14 Hz, 4H), 7.56 (m, J = 8.06 Hz, 2H), 8.19 (m, J = 8.19 Hz, 2H) 1.159 Me H 7.82-7.80 (2H, m), 7.50-7.48 (1H, m), 7.43-7.35 (2H, m), 7.29-7.27 (1H, m), 6.74 (1H, d), 3.78 (3H, s) 1.160 Me 0 H 8.29 (1H, s), 7.92 (1H, s), 7.68 (1H, s), 3.70 (3H, s), 3.17 (3H, s) 1.161 Me H 8.04 (1H, d), 7.96 (1H, d), 7.58 (1H, s), 3.90 (3H, s), 2.96 (3H, s) 1.163 CCCH.sub.2 H 2.24 (s, 3H), 2.45 (t, J = 2.55 Hz, 1H), 3.22 (s, 3H), 3.40 (br. s., 2H), 4.61 (t, J = 10.00 Hz, 2H), 5.04 (d, J = 2.42 Hz, 2H), 7.51 (d, J = 8.19 Hz, 1H), 7.71 (s, 1H), 8.09 (d, J = 8.19 Hz, 1H) 1.164 Me H 9.13 (m, 1H), 8.08 (s, 1H), 7.70 (s, 1H), 7.28 (s, 1H), 3.95 (m, 4H), 3.90 (s, 3H), 3.42 (m, 4H) 1.165 Me H 7.84 (s, 1H), 7.32- 7.34 (dd, 1H), 7.21- 7.25 (m, 1H), 6.89- 6.92 (m, 2H), 3.79 (s, 3H);

(133) TABLE-US-00002 TABLE C2 Examples of herbicidal compounds of the present invention. CMP R.sup.1 R.sup.3 R.sup.5 R.sup.6 R.sup.7 R.sup.8 R.sup.9 NMR 2.001 -allyl H S(O).sub.2Me H H H H 8.20 (1H, dd, J = 7.9, 1.3 Hz), 7.71-7.77 (2H, m), 7.64-7.71 (1H, m), 7.38 (1H, dd, J = 7.5, 1.2 Hz), 6.04 (1H, ddt, J = 17.3, 10.0, 6.0, 6.0 Hz), 5.27-5.35 (2H, m), 4.83 (2H, d, J = 19.7 Hz), 3.01 (3H, s) 2.002 Methoxy- H H CF.sub.3 H H H 8.48 (1H, br s), 8.00 (1H, methyl- dd), 7.73 (1H, s),7.55 (1H, d), 5.52 (2H, br s), 3.54 (3H, s), 3.04 (3H, s) 2.003 Methoxy- H SOEt H H H H 8.11 (1H, dd), 7.76 (1H, s), methyl- 7.70 (1H, td), 7.61 (1H, td), 7.35 (1H, dd), 5.54 (1H, d), 5.51 (1H, d), 3.54 (3H, s), 2.84-2.75 (1H, m), 2.70- 2.61 (1H, m), 1.18 (3H, t) 2.004 Methoxy- H SO.sub.2Et H H H H 8.16 (1H, dd), 7.77-7.73 methyl- (1H, m), 7.75 (1H, s), 7.68 (1H, td), 7.39 (1H, dd), 5.52 (2H, br d), 3.53 (3H, s), 3.02 (2H, q), 1.21 (3H, t) 2.005 Methoxy- H S(O).sub.2Me Cl H H H 8.20 (1H, d), 7.72 (1H, dd), methyl- 7.71 (1H, s), 7.33 (1H, d), 5.51 (2H, br s), 3.53 (3H, s), 3.01 (3H, s) 2.006 Methoxy- H S(O).sub.2Me F H H H 7.93 (1H, dd), 7.72 (1H, s), methyl- 7.48-7.43 (1H, m), 7.39 (1H, dd), 5.52 (2H, br s), 3.53 (3H, s), 3.01 (3H, s) 2.007 i-butyl H Me S(O).sub.2Me H H 8.09 (1H, d, J = 8.1 Hz), 7.65 (1H, s), 7.48-7.56 (1H, m), 4.61 (2H, t, J = 9.9 Hz), 4.07 (2H, d, J = 7.5 Hz), 3.39 (2H, br. s.), 3.22 (3H, s), 2.35 (1H, dt, J = 13.6, 6.9 Hz), 2.24 (3H, s) 1.00 (6H, d, J = 6.4 Hz) 2.008 p-methoxy- H S(O).sub.2Me Cl H H H benzyl- 2.009 -ethynyl H Me Cl H H 2.010 -ethynyl H S(O).sub.2Me CF.sub.3 H H H 8.5 (1H, br s), 8.0 (1H, d), 7.7 (1H, s), 7.5 (1H, d), 5.0 (2H, br d), 3.0 (3H, s), 2.4 (1H, m) 2.011 -ethynyl H S(O).sub.2Me Cl H H H 8.2 (1H, s), 7.7 (2H, m), 7.3 (1H, d), 5.0 (2H, br d), 3.0 (3H, s), 2.4 (1H, m) 2.012 CHF.sub.2CH.sub.2 H S(O).sub.2Me H H H H 8.20 (1H, dd, J = 7.9, 1.1 Hz), 7.64-7.81 (3H, m), 7.35-7.43 (1H, m), 4.69 (1H, br. s.), 4.46 (1H, br. s.), 3.00 (3H, s) 2.013 CH.sub.3CCCH.sub.2 H S(O).sub.2Me H H H H 8.21 (1H, dd, J = 7.9, 1.3 Hz), 7.72-7.79 (2H, m), 7.69 (1H, dd, J = 7.7, 1.4 Hz), 7.38 (1H, dd, J = 7.6, 1.3 Hz), 4.75-5.15 (1H, m), 3.54-3.80 (1H, m), 3.00 (3H, s), 1.87 (3H, t, J = 2.4 Hz) 2.014 c-Propyl- H S(O).sub.2Me Cl H H H 8.19 (1H, d, J = 2.1 Hz), 7.69 (1H, dd, J = 8.2, 2.1 Hz), 7.63 (1H, s), 7.30 (1H, d, J = 8.2 Hz), 4.15 (1H, tt, J = 7.7, 3.9 Hz), 3.00 (4H, s), 1.26 (2H, br. s.), 1.06 (2H, dd, J = 7.5, 1.6 Hz) 2.015 c-Propyl H S(O).sub.2Me CF.sub.3 H H H 8.48 (1H, s), 7.96-8.01 (1H, m), 7.65 (1H, s), 7.53 (1H, d, J = 7.9 Hz), 4.16 (1H, dt, J = 7.8, 3.7 Hz), 3.03 (3H, s), 1.27 (2H, br. s.), 1.07 (2H, dd, J = 7.5, 1.6 Hz) 2.016 Ethyl H S(O).sub.2Me CF.sub.3 H H H 8.5 (1H, s), 8.0 (1H, d), 7.7 e (1H, s), 7.5 (1H, d), 4.3 (2H, br q), 3.0 (3H, s), 1.5 (3H, t) 2.017 Ethyl H S(O).sub.2Me Cl H H H 8.2 (1H, br s), 7.8 (1H, dd), 7.6 (1H, s), 7.4 (1H, d), 4.3 (2H, br m), 3.1 (3H, s), 1.4 (3H, t) 2.018 i-propyl H Cl H Cl H H 2.019 Methyl cPr S(O).sub.2Me H H H 0.71-0.82 (2H, m) 0.87- 1.07 (2H, m) 1.21-1.32 (1H, m) 2.18 (3H, s) 3.23 (3H, s) 3.41 (2H, br. s.) 3.81 (3H, s) 4.60 (2H, t, J = 9.9 Hz) 7.48 (1H, d, J = 8.1 Hz) 8.09 (1H, d, J = 8.1 Hz) 2.020 Methyl vinyl S(O).sub.2Me H H H 2.13 (3H, s) 3.24 (3H, s) 3.40 (2H, br. s.) 3.93 (3H, s) 4.60 (2H, t, J = 9.9 Hz) 5.29-5.34 (1H, m) 5.95- 6.10 (2H, m) 7.41 (1H, d, J = 8.1 Hz) 8.09 (1H, d, J = 8.1 Hz) 2.021 Methyl S(O).sub.2Et Me S(O).sub.2Me H H 0 1.40 (3H, t, J = 7.3 Hz) 2.17 (3H, s) 3.22 (3H, s) 3.30- 3.61 (2H, m and 2H, br s) 3.95 (3H, s) 4.58 (2H, t, J = 9.9 Hz) 7.51 (1H, d, J = 8.1 Hz) 8.06 (1H, d, J = 8.1 Hz) 2.022 Methyl NO.sub.2 S(O).sub.2Me CF.sub.3 H H H 8.40 (1H, br d), 8.02 (1H, dd), 7.53 (1H, d), 3.99 (3H, s), 2.98 (3H, s) 2.023 Methyl CH2C(CH3) Me H H H 1.83 (3H, d, J = 1.6 Hz) 2.16 (3H, s) 3.23 (3H, s) 3.29- 3.48 (2H, br s) 3.91 (3H, s) 4.60 (2H, t, J = 9.9 Hz) 4.76 (1H, s) 5.13 (1H, s) 7.38 (1H, d, J = 8.1 Hz) 8.03 (1H, d, J = 8.1 Hz) 2.024 Methyl i-Pr Me S(O).sub.2Me H H 1.07 (3H, d, J = 7.0 Hz) 1.10 (3H, d, J = 7.0 Hz) 2.13 (3H, s) 2.42-2.54 (1H, m) 3.24 (3H, s) 3.33-3.50 (2H, br s) 3.88 (3H, s) 4.60 (2H, t, J = 10.2 Hz) 7.40 (1H, d, J = 8.1 Hz) 8.08 (1H, d, J = 8.6 Hz) 0039 2.025 Methyl CN Me S(O).sub.2Me H H 2.23 (3H, s) 3.24 (3H, s) 3.30-3.51 (2H, br s) 3.98 (3H, s) 4.61 (2H, t, J = 10.2 Hz) 7.52 (1H, d, J = 8.1 Hz) 8.14 (1H, d, J = 8.6 Hz) 2.026 Methyl H S(O).sub.2Me H Br H 7.98 (1H, d), 7.56 (1H, s), 7.45 (1H, d), 3.88 (7H, s overlapping with br s), 3.36 (3H, s), 3.17 (2H, br m), 2.96 (2H, br m) 2.027 Methyl H S(O).sub.2Me Br Br H 8.18 (1H, s), 7.55 (1H, s), 4.22-4.17 (1H, m), 3.97- 3.95 (1H, m), 3.91-3.83 (3H, m), 3.87 (3H, s), 3.79- 3.74 (1H, m), 3.34 (3H, s), 2.99-2.97 (1H, m), 2.73- 2.71 (1H, m) 2.028 Methyl H S(O).sub.2Me CC H H H 8.31 (1H, d), 7.80 (1H, dd), 7.68 (1H, s), 7.33 (1H, d), 3.88 (3H, s), 3.28 (1H, s), 2.99 (3H, s) 2.029 Methyl H S(O).sub.2Me CCCH.sub.3 H H H 8.20 (1H, d), 7.69 (1H, dd), 7.68 (1H, s), 7.27 (1H, d), 3.87 (3H, s), 2.98 (3H, s), 2.10 (3H, s) 2.030 Methyl H S(O).sub.2Me CF.sub.3CH.sub.2O H H H 7.75 (1H, d), 7.68 (1H, s), 7.35-7.29 (2H, m), 4.50 (1H, d), 4.46 (1H, d), 3.88 (3H, s), 2.98 (3H, s) 2.031 Methyl H S(O).sub.2Me Me H H H 8.01 (1H, m), 7.69 (1H, s), 7.54-7.52 (1H, m), 7.25 (1H, d), 3.88 (3H, s), 2.97 (3H, s), 2.51 (3H, s) 2.032 Methyl H S(O).sub.2Me NO.sub.2 H H H 9.06 (1H, d), 8.57 (1H, dd), 7.69 (1H, s), 7.61 (1H, d), 3.90 (3H, s), 3.06 (3H, s) 2.033 Methyl H S(O).sub.2Me -phenyl H H H 8.42 (1H, d), 7.94 (1H, dd), 7.75 (1H, s), 7.68-7.66 (2H, m), 7.53-7.43 (4H, m), 3.90 (3H, s), 3.03 (3H, s) 2.034 Methyl H S(O).sub.2Me NH.sub.2C(O) H H H 2.035 Methyl H S(O).sub.2Me Benzyl-S H H H 8.05 (1H, d), 7.66 (1H, s), 7.55 (1H, dd), 7.40-7.28 (5H, m), 7.21 (1H, d), 4.25 (2H, s), 3.87 (3H, s), 2.92 (3H, s) 2.036 Methyl H S(O).sub.2Me Benzyl-S(O).sub.2 H H H 8.39 (1H, d), 7.94 (1H, dd), 7.65 (1H, s), 7.45 (1H, d), 7.38-7.30 (3H, m), 7.16- 7.15 (2H, m), 4.42 (2H, s), 3.89 (3H, s), 2.94 (3H, s) 2.037 Methyl H S(O).sub.2Me H H H 8.55 (1H, d), 8.10 (1H, dd), 7.71 (1H, s), 7.58 (1H, d), 3.90 (3H, s), 3.80 (4H, m), 3.12 (4H, m), 3.04 (3H, s) 2.038 Methyl H S(O).sub.2Me (CH.sub.3).sub.2CHN(CH.sub.3)S(O).sub.2 H H H 8.59 (1H, d), 8.15 (1H, dd), 7.69 (1H, s), 7.52 (1H, d), 4.31 (1H, pent), 3.89 (3H, s), 3.03 (3H, s), 2.80 (3H, s), 1.10 (6H, d) 2.039 Methyl NH.sub.2 S(O).sub.2Me CF.sub.3 H H H 2.040 Methyl H S(O).sub.2Me CH.sub.3OCH.sub.2 H H H 8.16 (1H, br d), 7.71 (1H, br dd), 7.69 (1H, s), 7.35 (1H, d), 4.58 (2H, s), 3.88 (3H, s), 3.48 (3H, s), 2.99 (3H, s) 2.041 Methyl CH.sub.3O S(O).sub.2Me CF.sub.3 H H H 8.43 (1H, br d), 7.97 (1H, br dd), 7.47 (1H, d), 3.78 (3H, s), 3.75 (3H, s), 3.01 (3H, s) 2.042 Methyl H S(O).sub.2Me C(O)OH H H H 2.043 Methyl H S(O)2Me i-Pr-OCH.sub.2 H H H 8.16 (1H, d), 7.73 (1H, dd), 7.69 (1H, s), 7.34 (1H, d), 4.62 (2H, s), 3.86 (3H, s), 3.76 (1H, pent), 2.99 (3H, s), 1.27 (6H, d) 2.044 Methyl H S(O)2Me c-hexyl-CH.sub.2OCH.sub.2 H H H 2.045 Methyl H S(O).sub.2Me H H H 2.046 Methyl H S(O).sub.2Me H H H 2.047 Methyl H S(O).sub.2benzyl CF.sub.3 H H H 7.90 (1H, dd), 7.69 (1H, br d), 7.64 (1H, s), 7.53 (1H, d), 7.34-7.31 (1H, m), 7.26- 7.22 (2H, m), 7.08-7.07 (2H, m), 4.28 (2H, s), 3.91 (3H, s) 2.048 Methyl H S(O).sub.2N(CH.sub.3)(i-Pr) CF.sub.3 H H H 2.049 Methyl H CF.sub.3 H H H 8.30 (1H, d), 7.94 (1H, dd), 7.73 (1H, s), 7.56 (1H, d), 3.88 (3H, s), 3.65-3.62 (4H, m), 2.98 (4H, br s) 2.050 Methyl EtO S(O).sub.2Me CF.sub.3 H H H 8.43 (1H, br d), 7.96 (1H, dd), 7.47 (1H, d), 4.17 (2H, q), 3.76 (3H, s), 3.01 (3H, s), 1.19 (3H, t) 2.051 Methyl nPr-O S(O).sub.2Me CF.sub.3 H H H 8.43 (1H, br d), 7.96 (1H, dd), 7.47 (1H, d), 4.05 (2H, t), 3.76 (3H, s), 3.01 (3H, s), 1.61-1.52 (2H, m), 0.78 (3H, t) 2.052 Methyl iPr-O S(O).sub.2Me CF.sub.3 H H H 8.42 (1H, br d), 7.96 (1H, dd), 7.44 (1H, d), 5.01 (1H, pent), 3.76 (3H, s), 3.01 (3H, s), 1.19 (3H, d), 1.16 (3H, d) 2.053 Methyl H S(O).sub.2Me CF.sub.3CH.sub.2OCH.sub.2 H H H 8.16 (1H, d), 7.75 (1H, dd), 7.69 (1H, s), 7.39 (1H, d), 4.82 (2H, s), 3.97 (2H, q), 3.88 (3H, s), 2.99 (3H, s) 2.054 Vinyl H S(O).sub.2Me H H H H 8.20 (1H, dd, J = 7.9, 1.1 Hz) 7.81 (1H, td, J = 7.6, 1.4 Hz) 7.74 (1H, td, J = 7.7, 1.3 Hz) 7.70 (1H, s) 7.40 (1H, dd, J = 7.5, 1.2 Hz) 5.18 (1H, d, J = 16.5 Hz) 4.82 (1H, d, J = 16.5 Hz) 3.83 (3H, s) 3.00 (3 H, s) 2.055 H H Cl S(O).sub.2Me H H 00 8.17 (1H, d, J = 8.1 Hz), 7.76 (1H, s), 7.69 (1H, d, J = 8.6 Hz), 4.64 (2H, t, J = 10.2 Hz), 3.47 (2H, t, J = 10.2 Hz), 3.28 (3H, s) 2.056 Me OH S(O).sub.2Me CF.sub.3 H H H 8.37 (1H, br d), 8.06 (1H, br dd), 7.61 (1H, d), 3.66 (3H, s), 3.14 (3H, s) 2.057 Me H S(O).sub.2Me CH.sub.3OC.sub.2H.sub.5OCH.sub.2 H H H 8.17 (1H, d), 7.74 (1H, dd), 7.69 (1H, s), 7.34 (1H, d), 4.70 (2H, s), 3.88 (3H, s), 3.74-3.72 (2H, m), 3.64- 3.62 (2H, m), 3.42 (3H, s), 2.99 (3H, s)

(134) TABLE-US-00003 TABLE C3 Examples of herbicidal compounds of the present invention. 01 Cmp R.sup.1 R.sup.4 R.sup.5 R.sup.6 NMR 3.001 Methyl CH.sub.3C(O) S(O).sub.2Me CF.sub.3 8.49 (1H, br d), 7.98 (1H, dd), 7.77 (1H, s), 7.52 (1H, d), 3.88 (3H, s), 3.02 (3H, s), 2.21 (3H, s) 3.002 Methyl Phenyl-C(O) S(O).sub.2Me CF.sub.3 8.46 (1H, br d), 7.97-7.94 (3H, m), 7.83 (1H, s), 7.64-7.60 (2H, m), 7.46- 7.42 (2H, m), 3.91 (3H, s), 3.09 (3H, s) 3.003 Methyl CH.sub.3OC(O) S(O).sub.2Me CF.sub.3 8.48 (1H, br d), 8.00 (1H, dd), 7.78 (1H, s), 7.54 (1H, d), 3.90 (3H, s), 3.88 (3H, s), 3.03 (3H, s) 3.004 Methyl C.sub.2H.sub.5SC(O) S(O).sub.2Me CF.sub.3 8.48 (1H, br d), 7.99 (1H, dd), 7.76 (1H, s), 7.53 (1H, d), 3.89 (3H, s), 3.02 (3H, s), 2.91 (2H, q), 1.30 (3H, t) 3.005 Methyl nPr-S(O).sub.2 S(O).sub.2Me CF.sub.3 8.44 (1H, br d), 8.03 (1H, br dd), 7.78 (1H, s), 7.64 (1H, d), 3.90 (3H, s), 3.91-3.85 (1H, m), 3.79-3.73 (1H, m), 3.07 (3H, s), 2.01-1.95 (2H, m), 1.10 (3H, t) 3.006 Methyl 4-Me-phenyl- S(O).sub.2Me CF.sub.3 8.43 (1H, br d), 8.00 (1H, br dd), 7.8 S(O).sub.2 (2H, d), 7.77 (1H, s), 7.65 (1H, d), 7.33 (2H, d), 3.87 (3H, s), 3.06 (3H, s), 2.45 (3H, s)

(135) TABLE-US-00004 TABLE C4 Examples of herbicidal compounds of the present invention. 02 Compound R.sup.1 R.sup.5 R.sup.6 NMR 4.001 Ethyl- SO.sub.2Me CF.sub.3 8.1 (1H, d), 8.0 (1H, d), 7.9 (1H, br s), 4.3 (2H, q), 3.4 (3H, s), 1.4 (3H, t) 4.002 Methyl- 03 CF.sub.3 4.003 Methyl- SO.sub.2Me CF.sub.3 3.41 (3 H, s) 3.86 (3 H, s) 7.85 (1 H, s) 8.00 (1 H, d, J = 8.1 Hz) 8.13 (1 H, d, J = 8.1 Hz) 4.004 Methyl- 04 CF.sub.3 1.14 (6 H, d, J = 5.9 Hz) 2.58-2.69 (21 H, m) 3.41 (2 H, d, J = 10.7 Hz) 3.64-3.76 (2 H, m) 3.88 (3 H, s) 7.31 (1 H, d, J = 8.1 Hz) 7.86 (1 H, d, J = 7.0 Hz) 7.95 (1 H, s) 4.005 Methyl- CH.sub.3O CF.sub.3 11.28 (br s, 1 H) 7.97 (d, J = 7.5 Hz, 1 H) 7.77 (s, 1 H) 7.53 (d, J = 7.5 Hz, 1 H) 3.85 (s, 3 H) 3.65 (s, 3 H); 4.006 Methyl- OH CF.sub.3 12.21 (br. s., 1 H) 7.90 (d, J = 8.1 Hz, 1 H) 7.77 (s, 1 H) 7.35 (d, J = 7.0 Hz, 1 H) 3.65 (s, 3 H); 4.007 Methyl- HOC(O)CH.sub.2O CF.sub.3 4.008 Methyl- Ph-O CF.sub.3 3.88 (3 H, s) 7.14-7.19 (2 H, m) 7.19-7.24 (1 H, m) 7.36-7.42 (2 H, m) 7.49 (1 H, d, J = 8.1 Hz) 8.01 (1 H, s) 8.07 (1 H, d, J = 8.6 Hz) 4.009 Methyl 3-Cl-benzyl-O CF.sub.3 3.87 (3 H, s) 5.46 (2 H, s) 7.27-7.35 (3 H, m) 7.40 (1 H, d, J = 7.5 Hz) 7.45 (1 H, s) 7.89 (1 H, s) 7.97 (1 H, d, J = 7.5 Hz) 4.010 Methyl 05 CF.sub.3 3.88 (3 H, s) 7.63 (1 H, s) 7.85 (1 H, d, J = 7.5 Hz) 7.95 (1 H, s) 8.11 (1 H, d, J = 8.1 Hz) 9.08 (1 H, s) 4.011 Methyl CHF.sub.2CH.sub.2O H 7.87-8.10 (m, 2 H) 7.59 (s, 1 H) 7.02 (dd, J = 7.5, 4.8 Hz, 1H) 6.30 (tt, J = 54.8, 3.8 Hz, 1 H) 4.50 (td, J = 15.0, 3.2 Hz, 2 H) 3.53 (s, 3 H); 4.012 Methyl C.sub.2H.sub.5OC(O)O CF.sub.3 4.013 Methyl CH.sub.2CHCH.sub.2O CF.sub.3 4.014 Methyl Cl CF.sub.3 3.90 (3 H, s) 7.75 (1 H, d, J = 8.1 Hz) 7.79 (1 H, s) 7.97 (1 H, d, J = 7.0 Hz) 4.015 Methyl CN CF.sub.3 3.71 (1 H, s) 7.46-7.53 (1 H, m) 8.10-8.16 (1 H, m) 8.19 (1 H,s) 4.016 Methyl 06 CF.sub.3 3.54-3.63 (4 H, m) 3.76-3.83 (4 H, m) 3.89 (3 H, s) 7.89 (1 H, s) 7.94 (1 H, d, J = 8.1 Hz) 8.10 (1 H, d, J = 8.1 Hz) 4.017 Methyl (CH3).sub.2CHN(CH.sub.3)SO.sub.2 CF.sub.3 1.23 (6 H, d, J = 6.4 Hz) 2.99 (3 H, s) 3.88 (3 H, s) 4.20 (1 H, dt, J = 13.4, 6.7 Hz) 7.89 (1 H, s) 7.91 (1 H, d, J = 2.7 Hz) 8.06 (1 H, d, J = 7.5 Hz) 4.018 Methyl S(O).sub.2Et CN 4.019 Methyl S(O).sub.2NH.sub.2 CF.sub.3

(136) TABLE-US-00005 TABLE C5 Examples of herbicidal compounds of the present invention. 07 Com- pound R.sup.1 R5 R13a R13b NMR 5.001 Ethyl CF.sub.3 H H 9.3 (1H, m), 8.4 (1H, s), 8.3 (1H, d), 7.7 (1H, s), 7.6 (1H, d), 4.4 (2H, q), 1.5 (3H, t) 5.002 Methyl CF.sub.3 Methyl Methyl 2.72 (s, 3 H), 2.83 (s, 3 H), 3.92 (s, 3 H), 7.39 (s, 1 H), 7.72 (s, 1 H), 8.41 (s, 1 H)

(137) TABLE-US-00006 TABLE C6 Examples of herbicidal compounds of the present invention. 08 Compound R.sup.1 R.sup.8 R.sup.7 NMR 6.001 Methyl Methyl -phenyl 2.48 (3 H, s) 3.84 (3 H, s) 7.39-7.4 (1 H, m) 7.47-7.53 (2 H, m) 7.57- 7.62 (2H, m) 7.63 (1 H, s) 8.25 (1 H, s) 6.002 Methyl Methyl 09 2.49 (3 H, s) 3.85 (3 H, s) 7.32-7.37 (1 H, m) 7.55 (1 H, s) 7.63 (1 H, dd, J = 5.4, 1.6 Hz) 8.03-8.08 (1 H, m) 8.22 (1 H, s) 6.003 Methyl Methyl n-butyl 0.97 (3 H, t, J = 7.3 Hz) 1.41 (21 H, dd, J = 15.0, 7.5 Hz) 1.77-1.87 (2 H, m) 2.42 (3 H, s) 3.83 (3 H, s) 4.19-4.26 (2 H, m) 7.47 (1 H, s) 8.08 (1 H, s)

(138) TABLE-US-00007 TABLE C7 Examples of herbicidal compounds of the present invention. 0 Compound R.sup.6 R.sup.9 NMR 7.001 4-CF.sub.3-phenyl- 9.51 (s, 1 H) 7.83-7.91 (m, 3 H) 7.79 (d, J = 7.0 Hz, 1 H) 7.75 (d, J = 7.0 Hz, 1 H) 7.68 (d, J = 7.5 Hz, 2 H) 6.46 (t, J = 7.0 Hz, 1 H) 3.61 (s, 3 H) 7.002 CF.sub.3 3-NH.sub.2-phenyl- 7.003 CF.sub.3 3-MeO-phenyl- 7.83 (1H, s), 7.73 (1H, d), 7.41-7.37 (1H, m), 7.12-7.10 (1H, m), 7.05-7.03 (1H, m), 7.01-6.97 (1H, m), 6.70 (1H, d), 3.79 (3H, s), 3.77 (3H, s) 7.004 CF.sub.3 3-CH.sub.3C(O)NH- phenyl- 7.005 CF.sub.3 3-CF.sub.3O-phenyl- 7.88 (1H, s), 7.79 (1H, d), 7.55-7.51 (1H, m), 7.35-7.29 (2H, m), 7.23 (1H, m), 6.75 (1H, d), 3.79 (3H, s) 7.006 CF.sub.3 4-CH.sub.3-phenyl- 7.85 (1H, s), 7.72 (1H, dd), 7.24 (2H, d), 7.15 (2H, d), 6.71 (1H, d), 3.78 (3H, s), 2.38 (3H, s) 7.007 CF.sub.3 2-CH.sub.3,5F- 7.86 (1H, s), 7.81 (1H, dd), 7.27 (1H, dd), 7.05 (1H, td), 6.89 phenyl (1H, dd), 6.76 (1H, d), 3.79 (3H, s), 2.10 (3H, s) 7.008 CF.sub.3 3-MeS(O).sub.2NH 7.009 CF.sub.3 4-NO.sub.2-phenyl 8.31 (2H, d), 7.87 (1H, s), 7.83 (1H, dd), 7.57 (2H, d), 6.78 (1H, d), 3.79 (3H, s) 7.010 CF.sub.3 3.85 (3H, s), 6.65 (1H, d), 7.4-7.8 (4H, m), 7.85 (1H, s) 7.011 CF.sub.3 3-vinyl-phenyl- 3.8 (3H, s), 5.25 1H, d), 5.75 (1H, d), 6.6 (1H, d), 6.7 (1H, dd), 7.2-7.7 (5H, m), 7.8 (1H, s) 7.012 CF.sub.3 3-F-phenyl- 3.85 (3H, s), 6.6 (1H, d), 7.0-7.7 (5H, m), 7.9 (1H, s) 7.013 CF.sub.3 3-HC(O)-phenyl- 7.014 CF.sub.3 3-iPr-phenyl- 1.3 (6H, d), 2.9 (1H, m), 3.85 (3H, s), 6.7 (1H, d), 7.1-7.4 (5H, m), 7.9 (1H, s) 7.015 CF.sub.3 2-MeO,5-iPr- 1.2 (6H, d), 2.9 (1H, m), 3.85 (3H, s), 6.6 (1H, d), 6.9-7.45 (4H, phenyl- m), 7.9 (1H, s) 7.016 CF.sub.3 3-EtO-phenyl- 1.4 (3H, t), 3.85 (3H, s), 4.05 (2H, q), 6.6 (1H, d), 6.8-7.7 (5H, m), 7.9 (1H, s) 7.017 CF.sub.3 3,4,5 3.85 (3H, s), 6.6 (1H, d), 6.9-7.7 (3H, m), 7.9 (1H, s) trifluorophenyl- 7.018 CF.sub.3 3-CF.sub.3-phenyl- 3.85 (3H, s), 6.6 (1H, d), 7.4-7.7 (4H, m), 7.9 (1H, s) 7.019 CF.sub.3 3-CN-phenyl- 3.8 (3H, s), 6.7 (1H, d), 7.5-7.7 (4H, m), 7.9 (1H, s) 7.020 CF.sub.3 3-MeS-phenyl- 2.5 (3H, s), 3.85 (3H, s), 6.6 (1H, d), 7.1-7.7 (5H, m), 7.9 (1H, s) 7.021 CF.sub.3 3,4,5 trimethoxy- 3.89 (3H, s), 3.85 (3H, s), 3.84 (6H, s), 6.5 (2H, s), 6.6 (1H, d), phenyl- 7.4 (1H, d), 7.9 (1H, s) 7.022 CF.sub.3 3,5 dichlorophenyl- 3.8 (3H, s), 6.6 (1H, d), 7.2-7.5 (4H, m), 7.9 (1H, s) 7.023 CF.sub.3 3-MeS(O).sub.2-phenyl- 3.1 (3H, s), 3.8 (3H, s), 6.65 (1H, d), 7.5-8.0 (5H, m), 7.9 (1H, s) 7.024 CF.sub.3 3-(CH.sub.3).sub.2N-phenyl- 3.15 (6H, s), 3.85 (3H, s), 6.7 (1H, d), 7.2-7.55 (5H, m), 7.9 (1H, s) 7.025 CF.sub.3 3-(CH.sub.3).sub.2NS(O).sub.2- phenyl- 7.026 CF.sub.3 3-CN,4-Cl- 3.85 (3H, s), 6.6 (1H, d), 7.2-7.5 (4H, m), 7.85 (1H, s) phenyl- 7.027 CF.sub.3 3-NO.sub.2,4Me 2.65 (3H, s), 3.85 (3H, s), 6.6 (1H, d), 7.4-7.7 (3H, m), 7.9 (1H, phenyl- s), 8.0 (1H, s) 7.028 CF.sub.3 7.029 CF.sub.3 2,3-dichlorophenyl- 3.85 (3H, s), 6.6 (1H, d), 7.15-7.55 (4H, m), 7.9 (1H, s) 7.030 CF.sub.3 2-Me,3-Cl-phenyl- 2.2 (3H, s), 3.85 (3H, s), 6.6 (1H, d), 6.95-7.7 (4H, m), 7.9 (1H, s) 7.031 CF.sub.3 4-CN-phenyl- 3.85 (3H, s), 6.65 (1H, d), 7.45-7.75 (5H, m), 7.85 (1H, s) 7.032 CF.sub.3 2-Cl,5-Me-phenyl- 2.35 (3H, s), 3.85 (3H, s), 6.6 (1H, d), 7.05-7.5 (4H, m), 7.9 (1H, s) 7.033 CF.sub.3 4-MeO-phenyl- 3.84 (3H, s), 3.85 (3H, s), 6.6 (1H, d), 6.9-7.4 (5H, m), 7.9 (1H, s) 7.034 CF.sub.3 2-vinylphenyl- 3.85 (3H, s), 5.3 (1H, d), 5.8 (1H, d), 6.6 (1H, d), 6.75 (1H, dd), 7.1-7.7 (5H, m), 7.9 (1H, s) 7.035 CF.sub.3 4-CF.sub.3-phenyl- 3.85 (3H, s), 6.6 (1H, d), 7.4-7.7 (5H, m), 7.9 (1H, s) 7.036 CF.sub.3 4-MeS-phenyl- 2.5 (3H, s), 3.85 (3H, s), 6.6 (1H, d), 7.2-7.7 (5H, m), 7.9 (1H, s) 7.037 CF.sub.3 4-CH(O)-phenyl- 7.038 CF.sub.3 2-Me,4-Cl-phenyl- 2.15 (3H, s), 3.85 (3H, s), 6.6 (1H, d), 7.05-7.5 (4H, m), 7.9 (1H, s) 7.039 CF.sub.3 2,4 dichlorophenyl- 3.85 (3H, s), 6.6 (1H, d), 7.15-7.55 (4H, m), 7.9 (1H, s) 7.040 CF.sub.3 7.041 CF.sub.3 2-Cl,4-CF.sub.3 phenyl- 3.85 (3H, s), 6.6 (1H, d), 7.15-7.5 (4H, m), 7.9 (1H, s) 7.042 CF.sub.3 2-Me,4-CN- 2.2 (3H, s), 3.85 (3H, s), 6.65 (1H, d), 7.2-7.6 (4H, m), 7.9 (1H, phenyl- s)

(139) TABLE-US-00008 TABLE C8 Examples of herbicidal compounds of the present invention. Compound R.sup.1 R.sup.5 R.sup.6 NMR 8.001 Methyl CF.sub.3 2.96-3.10 (2 H, m) 3.22-3.33 (2 H, m) 3.45-3.54 (2 H, m) 3.63-3.76 (10 H, m) 3.79 (3 H, s) 7.52 (1 H, s) 8.19 (1 H, s)

(140) TABLE-US-00009 TABLE C9 Examples of herbicidal compounds of the present invention. Compound R.sup.6 R.sup.9 NMR 9.001 CF.sub.3 8.26 (t, J = 8.1 Hz, 1 H) 8.08 (d, J = 8.6 Hz, 1 H) 8.00 (d, J = 8.1 Hz, 1 H) 7.90 (dd, J = 7.0, 2.1 Hz, 1 H) 7.77 (dd, J = 7.0, 2.1 Hz, 1 H) 6.51 (t, J = 7.0 Hz, 1 H) 3.63 (s, 3 H); 9.002 H CH2CHCH.sub.2 7.93 (s, 1 H) 7.88 (dd, J = 7.0, 1.6 Hz, 1 H) 7.74 (dd, J = 6.4, 1.6 Hz, 1 H) 6.56 (t, J = 7.0 Hz, 1 H) 5.97-6.08 (m, 1 H) 5.17-5.30 (m, 2 H) 4.71 (dt, J = 5.4, 1.6 Hz, 2 H) 3.77 (s, 3 H) 9.003 H Methyl 7.91-7.94 (m, 1 H) 7.88 (dd, J = 7.0, 2.1 Hz, 1 H) 7.80 (dd, J = 6.4, 2.1 Hz, 1 H) 6.54 (t, J = 7.0 Hz, 1 H) 3.77 (s, 3H) 3.66 (s, 3 H) 9.004 H 4-MeO-benzyl- 7.91 (s, 1 H) 7.80-7.88 (m, 2 H) 7.28-7.35 (m, 2 H) 6.87-6.92 (m, 2 H) 6.54 (t, J = 7.0 Hz, 1 H) 5.21 (s, 2 H) 3.76 (d, J = 1.1 Hz, 6 H); 9.005 H CF.sub.3CH.sub.2 7.91 (s, 1 H) 7.89 (dd, J = 7.5, 1.6 Hz, 2 H) 7.70-7.75 (m, 1 H) 6.54 (t, J = 7.0 Hz, 1 H) 4.89 (q, J = 8.6 Hz, 2 H) 3.77 (s, 3 H) 9.006 H cPr-CH.sub.2 7.93 (s, 1 H) 7.89 (dd, J = 7.5, 1.6 Hz, 1 H) 7.85 (dd, J = 6.4, 2.1 Hz, 1 H) 6.57 (t, J = 7.0 Hz, 1 H) 3.95 (d, J = 7.5 Hz, 2 H) 3.77 (s, 3 H) 1.29-1.40 (m, 1 H) 0.56-0.63 (m, 2 H) 0.42-0.49 (m, 2 H) 9.007 H CH.sub.3C(CH.sub.2)CH.sub.2 7.96 (br. s., 1 H) 7.90 (dd, J = 7.5, 1.6 Hz, 1 H) 7.71 (dd, J = 7.0, 1.6 Hz, 1 H) 6.58 (t, J = 7.0 Hz, 1 H) 4.96 (s, 1 H) 4.67 (s, 3 H) 3.77 (s, 3 H) 1.77 (s, 3 H) 9.008 H Benzyl- 7.92 (s, 1 H) 7.81-7.90 (m, 2 H) 7.31 (m, J = 4.3 Hz, 5 H) 6.55 (t, J = 7.0 Hz, 1 H) 5.29 (s, 2 H) 3.76 (s, 3 H) 9.009 H CH.sub.3OCH.sub.2CH.sub.2 7.94 (br. s., 1 H) 7.89 (dd, J = 7.0, 2.1 Hz, 1 H) 7.75 (dd, J = 6.4, 2.1 Hz, 1 H) 6.54 (t, J = 7.0 Hz, 1 H) 4.28 (t, J = 4.8 Hz, 1 H) 3.78 (s, 1 H) 3.71 (t, J = 5.4 Hz, 2 H) 3.34 (s, 2 H) 9.010 CF.sub.3 Me 7.93 (s, 1 H) 7.88 (d, J = 7.0 Hz, 1 H) 7.00 (d, J = 7.5 Hz, 1 H) 3.77 (s, 3 H) 3.69 (s, 3 H) 9.011 CF.sub.3 CH.sub.2CHCH.sub.2 8.12 (s, 1 H) 7.85 (d, J = 7.5 Hz, 1 H) 6.84 (d, J = 7.5 Hz, 1 H) 5.93 (m, J = 10.9, 10.9, 5.6 Hz, 1 H) 5.18-5.33 (m, 2 H) 4.78 (d, J = 4.8 Hz, 2H) 3.84 (s, 3H); 9.012 H 2.48 (3H, s), 3.83 (3H, s), 6.47 (1H, app.t), 6.68 (1H, m), 6.94 (1H, d), 7.68 (1H, d), 7.87 (1H, d), 8.09 (1H, s) 9.013 H 3.82 (3H, s), 6.51 (1H, app.t), 7.25 (1H, d), 7.44-7.51 (2H, m), 7.62 (1H, d), 7.91 (1H, d), 8.08 (1H, s) 9.014 H 0 3.82 (3H, s), 6.52 (1H, app.t), 7.03 (1H, m), 7.18 (1H, m), 7.28 (1H, m), 7.72 (1H, d), 7.86 (1H, d), 8.08 (1H, s) 9.015 H 3Cl,4-F-phenyl- 3.82 (3H, s), 6.50 (1H, app.t), 7.02 (1H, m), 7.33 (1H, m), 7.42 (1H, d), 7.53 (1H, d), 7.89 (1H, d), 8.03 (1H, s) 9.016 H 4-MeO-phenyl- 9.017 H 4-Me-phenyl 3.81 (3H, s), 6.53 (1H, app.t), 7.31-7.59 (6H, m), 7.89 (1H, d), 8.08 (1H, s) 9.018 H Phenyl- 2.53 (3H, s), 3.82 (3H, s), 6.51 (1H, app.t), 7.11 (2H, m), 7.21 (1H, m), 7.51 (1H, d), 7.89 (1H, m), 8.08 (1H, s) 9.019 H 3-F,4-Me-phenyl- 2.41 (3H, s), 3.78 (3H, s), 6.52 (1H, app.t), 7.20 (1H, d), 7.33-3.41 (2H, m), 7.50 (1H, d), 7.89 (1H, d), 8.05 (1H, s) 9.020 H 2-Cl,4-Me-phenyl- 3.79 (3H, s), 6.53 (1H, app.t), 7.47 (1H, d), 7.62 (2H, d), 7.84 (2H, d), 7.91 (1H, d), 8.06 (1H, s) 9.021 H 3-CN-phenyl- 9.022 H 9.023 H 3.80 (3H, s), 6.52 (1H, app.t), 7.38 (1H, d), 7.64 (1H, m), 7.94 (1H, d), 8.11 (1H, s), 8.21 (1H, d), 8.89 (1H, s) 9.024 H 3.81 (3H, s), 6.50 (1H, app.t), 7.34 (1H, d), 7.98 (1H, d), 8.09 (1H, s), 8.18 (1H, s), 8.79 (1H, s) 9.025 H 3.82 (3H, s), 6.51 (1H, app.t), 7.57 (1H, dd), 7.85 (1H, d), 7.92-8.00 (2H, m), 8.09 (1H, s), 8.41 (1H, s) 9.026 H 9.027 H

(141) TABLE-US-00010 TABLE C10 Examples of herbicidal compounds of the present invention. Compound R.sup.6 R.sup.7 NMR 10.001 H CH.sub.2CHCH.sub.2 3.85 (3 H, s) 4.64 (2 H, d, J = 5.9 Hz) 5.30-5.42 (2 H, m) 5.94-6.06 (1 H, m) 8.13 (1 H, s) 8.14-8.23 (1 H, m) 8.35- 8.43 (1 H, m) 10.002 3-Cl-phenyl- nPr 0.83 (3 H, t, J = 7.5 Hz) 1.70 (2 H, dd, J = 15.6, 7.5 Hz) 3.86 (3 H, s) 3.93-4.00 (2 H, m) 7.39-7.57 (4 H, m) 8.17 (1 H, s) 8.41 (1 H, s) 10.003 3-F-phenyl- chexyl- 0.95-1.09 (2 H, m) 1.14-1.29 (1 H, m) 1.57 (1 H, d, J = 14.0 Hz) 1.72 (2 H, d, J = 11.8 Hz) 1.81 (2 H, d, J = 12.9 Hz) 2.71 (2 H, td, J = 12.8, 9.4 Hz) 3.85 (3 H, s) 3.90-4.00 (1 H, m) 7.20-7.26 (1 H, m) 7.27-7.30 (1 H, m) 7.52 (1 H, td, J = 7.9, 5.6 Hz) 8.12 (1 H, s) 8.32 (1 H, s) 10.004 3-F-phenyl- 2-Me,5-C1 2.14 (3 H, s) 3.86 (3 H, s) 7.03-7.14 (4 H, m) 7.16-7.33 (3 phenyl- H, m) 8.24 (1 H, s) 8.63 (1 H, s) 10.005 c-propyl n-butyl 1.01 (3 H, t, J = 7.3 Hz) 1.14-1.22 (2 H, m) 1.30-1.35 (2 H, m) 1.49 (2 H, dq, J = 15.0, 7.4 Hz) 1.74 -1.85 (2 H, m) 2.01 (1 H, ddd, J = 12.5, 7.9, 4.8 Hz) 3.83 (3 H, s) 4.26-4.33 (2 H, m) 8.07 (1 H, s) 8.21 (1 H, s)

Biological Examples

(142) Seeds of a variety of test species are sown in standard soil in pots (Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Solanum nigrum (SOLNI), Amaranthus retoflexus (AMARE), Ipomoea hederacea (IPOHE)). After cultivation for one day (pre-emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16 C., day/night; 14 hours light; 65% humidity), the plants are sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64-5). Compounds are applied at 1000 g/h. The test plants are then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16 C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days for pre and post-emergence, the test is evaluated for the percentage herbicidal damage caused to the plant. The biological activities are shown in the following table on a five point scale (5=80-100% damage; 4=60-79% damage; 3=40-59% damage; 2=20-39% damage; 1=0-19% damage).

(143) TABLE-US-00011 TABLE B1 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 1.001 5 5 5 5 5 5 5 5 5 5 5 5 1.002 5 3 1 1 1 2 1 1 1 1 1 1 1.003 5 5 5 2 5 5 4 5 1 1 5 3 1.004 5 5 4 1 5 4 1 1 1 1 3 1 1.005 5 5 5 4 5 5 3 5 5 1 5 1 1.006 5 5 1 1 1 5 3 5 1 2 2 3 1.007 5 5 4 4 5 4 2 3 4 1 4 2 1.008 5 5 5 5 5 5 5 4 4 4 5 3 1.009 5 5 5 5 5 5 5 5 5 5 5 1.010 4 2 1 1 1 4 1 1 1 1 1 1 1.011 4 4 2 2 2 2 1 1 1 1 1 1 1.012 5 5 5 5 5 5 5 5 4 4 5 4 1.013 5 5 5 5 5 5 5 5 5 5 5 4 1.014 5 5 5 5 5 5 5 5 5 5 5 2 1.015 4 2 1 1 2 4 1 1 1 1 1.016 3 5 3 2 2 2 1 1 1 1 1 1 1.018 5 5 5 4 5 5 5 5 4 2 5 5 1.021 5 5 1 1 5 5 1 5 1 2 5 2 1.022 3 2 1 1 1 1 1 1 1 1 1 1 1.023 2 3 4 2 1 1 1 5 4 2 1 1 1.024 5 5 3 1 2 4 1 5 1 1 2 4 1.025 4 2 1 1 1 2 1 1 1 1 1 1 1.026 5 5 5 5 5 5 5 5 5 5 5 5 1.027 5 5 5 1 5 5 4 5 3 1 5 1 1.028 5 5 5 5 5 5 5 5 5 5 5 5 1.029 5 5 5 5 5 5 5 5 5 5 5 5 1.030 5 5 2 1 4 3 4 5 1 1 2 1 1.031 5 5 5 2 5 5 2 5 4 1 5 1 1.032 5 5 5 5 5 5 5 5 5 5 5 4 1.033 5 5 1 2 2 5 5 5 1 1 2 1 1.034 5 5 5 4 5 5 5 5 5 2 5 3 1.035 5 5 1 2 5 5 3 5 1 1 5 4 1.036 5 5 5 5 5 5 1 3 2 3 2 1 1.037 5 5 4 4 4 4 5 5 4 4 5 1 1.038 5 5 5 4 4 4 5 5 3 3 5 1 1.039 5 5 5 4 5 5 4 5 3 2 5 5 1.040 5 5 5 4 5 5 5 5 5 5 5 4 1.041 5 5 5 4 5 5 2 4 2 3 4 1 1.042 5 5 5 5 5 4 5 5 5 5 5 1 1.043 5 5 4 2 4 4 1 1 1 1 1 1 1.044 5 5 5 5 5 5 5 5 5 5 5 1 1.045 4 2 1 1 1 1 1 1 1 1 1 1 1.046 5 5 5 5 5 5 5 5 3 5 5 1 1.047 4 3 1 1 1 3 1 1 1 1 1 1 1.049 5 5 5 5 5 5 5 5 3 2 5 1 1.050 5 5 4 2 5 5 3 5 2 1 5 1 1.051 5 5 2 1 2 4 1 5 1 2 4 1 1.052 5 5 5 4 5 5 5 5 4 4 5 1 1.053 5 5 4 5 5 5 5 5 4 5 5 2 1.054 5 5 5 5 5 4 5 5 5 5 5 3 1.055 5 5 1 1 4 4 4 5 1 1 2 2 1.056 5 5 5 5 5 5 4 5 1 5 5 1 1.057 5 5 5 5 5 5 5 5 5 5 5 2 1.058 5 5 5 5 5 5 5 5 5 5 5 5 1.059 5 5 5 5 5 5 5 5 5 5 5 5 1.061 5 5 5 5 5 5 5 5 5 5 5 4 1.062 4 5 4 2 5 5 1 1 1 1 1 1.063 2 3 1 1 1 3 1 1 1 1 1 1 1.064 5 5 1 1 1 4 1 1 1 1 1 1 1.065 4 5 5 1 5 4 1 5 2 1 3 1.066 3 1 1 2 1 2 4 4 1 3 2 5 1.067 5 5 4 2 5 5 3 4 1 1 5 2 1.068 5 5 3 3 5 5 4 4 2 2 5 3 1.069 4 5 1 2 5 4 2 2 2 1 5 4 1.070 4 3 4 1 4 1 1 1 1 1 1 1 1.071 5 5 4 3 5 5 5 5 4 4 5 2 1.072 5 5 5 4 5 5 5 5 5 4 5 5 1.073 5 5 5 4 5 5 5 5 5 5 5 2 1.074 5 5 5 2 5 5 1 5 1 2 4 1 1.075 5 5 2 3 5 5 5 5 1 1 5 2 1.076 4 5 1 2 2 4 2 5 1 1 1 1 1.077 2 4 1 1 1 2 3 3 1 1 1 1 1.078 5 5 5 1 5 4 5 5 5 2 5 2 1.081 5 5 5 5 5 5 5 5 5 5 5 2 1.082 4 2 1 1 1 2 1 1 1 1 1 1 1.084 4 4 2 1 3 4 1 1 1 1 1 1 1.086 1 1 1 1 1 1 1 1 1 1 1 1 1.088 5 5 1 1 5 1 1 5 1 1 1 1 1.089 1 1 1 1 1 1 1 1 1 1 1 1 1.090 2 1 1 1 1 1 1 1 1 1 1 1 1.091 2 1 1 1 1 1 1 1 1 1 1 1 1.092 2 1 1 1 1 2 1 1 1 1 1 1 1.093 2 1 1 1 1 1 1 1 1 1 1 1 1.094 2 1 1 1 1 1 1 1 1 1 1 1 1.095 1 1 1 1 1 1 1 1 1 1 1 1 1.096 1 1 1 1 1 2 1 1 1 1 1 1 1.098 3 2 1 1 1 2 1 1 1 1 1 1 1.099 2 3 1 1 1 2 1 1 1 1 1 1 1.100 2 2 1 1 1 2 1 1 1 1 1 1 1.101 1 1 1 1 1 1 1 1 1 1 1 1 1.103 2 1 1 1 1 1 1 1 1 1 1 1 1.105 5 5 1 2 5 5 4 5 2 2 5 1 1.106 4 5 2 2 4 2 1 4 1 1 1 1 1.108 3 3 1 1 1 1 1 1 1 1 1 1 1.109 4 5 1 1 2 4 2 5 1 1 1 1 1.110 5 5 1 1 3 5 1 5 1 1 1 1 1.111 3 2 1 1 1 1 1 1 1 2 1.112 4 5 1 1 1 4 1 1 1 1 1 1 1.113 5 5 3 2 2 5 4 5 1 1 1 2 1.114 1 1 1 1 1 1 1 1 1 1 1 1 1.115 5 2 1 1 1 4 4 4 1 1 2 1.116 5 4 2 1 2 4 3 5 2 2 1 1 1.118 3 4 1 1 2 2 1 1 1 1 1 1 1.119 5 5 5 5 5 5 5 5 5 5 5 5 1.120 5 5 5 5 5 5 4 5 4 3 5 4 1.125 5 5 5 5 5 5 4 5 5 4 5 1 1.126 4 5 2 1 2 3 1 1 1 1 1 1.128 4 1 2 1 1 3 1 1 1 1 1 1 1.129 3 3 2 1 2 2 1 1 1 1 1 1 1.131 5 5 4 4 5 5 4 3 1 1 1 1 1.133 2 1 1 1 3 2 1 1 1 1 1 1 1.134 5 5 2 1 2 5 5 5 1 1 1 2 1.135 5 5 5 4 5 5 5 5 5 4 5 5 1.137 5 5 5 1 5 5 3 2 1 1 1 1 1.138 5 5 5 1 4 1 1 1 1 1 1 1 1.139 5 5 5 5 5 5 5 1 5 5 4 1.140 5 5 3 5 5 5 5 5 1 5 5 2 1.141 5 5 5 5 5 5 5 5 5 5 5 5 1.143 4 1 1 2 2 1 1 3 1 2 1 1 1.144 5 5 5 5 5 5 5 5 4 5 5 4 1.145 5 5 5 3 5 5 2 5 2 1 4 1 1.146 5 5 5 5 5 5 5 5 2 4 5 4 1.147 3 1 1 1 1 1 1 2 2 1 1 1 1.148 3 2 4 1 2 3 1 1 1 1 1 2 1.149 4 4 1 2 1 1 1 1 1 1 1 1 1.150 4 1 1 1 1 1 1 2 1 1 1 2 1.151 5 5 5 5 5 5 4 5 2 2 5 5 1.152 1 1 1 1 1 2 2 2 5 4 2 1 1.153 4 2 1 1 1 2 2 2 1 1 2 3 1.154 5 5 5 4 5 5 2 5 2 2 5 5 1.157 5 5 5 3 5 5 3 5 3 2 5 3 1.158 5 5 5 5 5 5 4 5 3 3 5 3 1.159 5 5 5 4 5 5 5 5 5 5 5 1 1.160 5 5 4 3 5 5 4 5 1 1 5 2 1.161 4 5 4 3 4 2 1 3 1 1 1 1 1.163 5 5 5 5 5 5 5 5 5 5 5 4 1.164 5 5 5 1 5 5 2 3 2 1 4 4 1.165 1 1 1 1 1 1 1 1 1 1 1 1 * Applied at 250 g/ha

(144) TABLE-US-00012 TABLE B2 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 2.001 5 5 5 5 5 5 5 5 5 5 5 5 2.002 5 5 5 5 5 5 5 5 5 5 5 5 2.003 5 5 4 3 5 4 1 5 4 3 4 1 2.004 5 5 5 3 5 5 5 5 5 5 5 4 2.005 5 5 5 5 5 5 5 5 5 5 5 5 2.006 5 5 5 5 5 5 5 5 5 5 5 5 2.007 5 5 5 2 5 5 4 5 1 1 5 3 2.008 5 5 5 3 5 5 5 5 2 4 5 3 2.010 5 5 5 5 5 5 5 5 5 5 5 5 2.011 5 5 5 5 5 5 5 5 5 5 5 5 2.012 5 5 5 5 5 5 5 5 5 5 5 5 2.014 5 5 5 5 5 5 5 5 5 5 5 5 2.015 5 5 5 5 5 5 5 5 5 5 5 5 2.016 5 5 5 5 5 5 5 5 5 5 5 5 2.017 5 5 5 5 5 5 5 5 5 5 5 5 2.019 5 5 4 5 4 5 5 5 2 4 5 4 2.020 5 5 4 4 4 5 5 5 1 4 5 1 2.021 5 5 2 1 5 5 1 5 1 1 1 1 2.022 5 5 5 5 5 5 5 5 4 5 5 5 2.023 5 5 5 5 5 5 5 5 1 5 5 4 2.024 5 5 5 5 5 5 4 5 4 5 5 4 2.025 5 5 1 2 4 4 5 5 1 1 1 5 2.026 5 4 3 3 4 2 4 5 1 1 2 1 2.027 5 5 4 4 5 5 3 5 1 2 5 3 2.028 5 5 5 5 5 5 5 5 4 5 5 4 2.029 5 5 5 5 5 5 5 5 3 5 5 1 2.030 5 5 5 5 5 5 5 5 5 5 5 4 2.031 5 5 5 4 5 5 5 5 5 4 5 3 2.032 5 5 4 3 5 5 5 5 2 2 5 3 2.033 5 5 3 5 5 5 5 5 2 4 4 1 2.035 5 5 5 4 5 5 5 5 2 3 3 3 2.036 5 5 5 5 5 5 5 5 5 5 5 5 2.037 5 5 4 3 5 5 5 5 2 3 5 4 2.038 5 5 5 4 5 4 5 5 4 5 5 4 2.039 5 5 5 5 5 5 5 5 5 5 5 5 2.040 5 5 5 5 5 5 5 5 4 5 5 3 2.041 5 5 5 5 5 5 5 5 5 5 5 5 2.043 5 5 4 3 5 5 5 5 1 3 5 2 2.047 5 5 3 3 5 4 4 2 1 1 5 1 2.049 5 5 1 1 5 5 5 5 2 1 5 4 2.050 5 5 5 5 5 5 5 5 5 5 5 5 2.051 5 5 5 5 5 5 5 5 3 5 5 4 2.052 5 5 5 5 5 5 5 5 3 4 5 4 2.053 5 5 2 3 3 5 5 5 2 3 5 1 2.054 5 5 5 5 5 5 5 5 5 5 5 4 2.055 5 5 5 3 5 3 2 4 1 2 2 1 2.056 5 5 5 5 5 5 5 5 5 4 5 3

(145) TABLE-US-00013 TABLE B3 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 3.001 5 5 5 5 5 5 5 5 5 5 5 5 3.002 5 5 5 5 5 5 5 5 5 5 5 5 3.003 5 5 5 5 5 5 5 5 5 5 5 5 3.004 5 5 5 5 5 5 5 5 5 5 5 5 3.005 5 5 5 5 5 5 5 5 5 5 5 4 3.006 5 5 5 5 5 5 5 5 5 5 5 4

(146) TABLE-US-00014 TABLE B4 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 4.001 5 5 5 5 5 5 5 5 5 5 5 5 4.003 5 5 5 5 5 5 5 5 5 5 5 5 4.004 5 5 2 1 3 5 3 5 1 1 3 4.005 3 5 1 1 1 2 1 5 1 1 1 1 4.006 4 3 1 1 1 2 1 1 1 1 1 1 4.008 5 5 2 1 2 4 1 5 1 1 1 1 4.009 5 4 1 1 1 1 1 3 1 1 1 1 4.010 5 5 4 3 5 5 5 5 1 1 5 5 4.011 5 4 1 1 1 3 1 1 1 1 1 1 4.014 5 5 2 1 3 5 4 5 1 1 5 2 4.015 1 1 1 1 1 1 1 1 1 1 1 1 4.016 5 5 5 5 5 5 5 5 5 5 5 5 4.017 5 5 5 5 5 5 5 5 4 4 5 5

(147) TABLE-US-00015 TABLE B5 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 5.001 5 5 5 5 5 5 5 5 5 5 5 5 5.002 5 5 2 1 3 5 1 5 1 1 2 3

(148) TABLE-US-00016 TABLE B6 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 6.001 5 5 3 3 5 1 1 1 1 1 1 1 6.002 3 4 1 1 1 2 5 5 1 1 1 2 6.003 4 4 2 2 4 2 1 1 1 1 1 1

(149) TABLE-US-00017 TABLE B7 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 7.001 4 3 3 2 4 2 1 1 1 1 1 1 7.003 5 5 3 4 5 3 5 5 4 4 4 3 7.005 5 5 4 4 5 4 5 5 4 4 5 1 7.006 5 4 3 3 5 3 5 5 4 3 5 2 7.007 5 5 5 5 5 5 5 5 5 5 5 4 7.009 5 5 5 5 5 5 5 5 5 5 5 4 7.010 5 5 5 5 5 5 5 5 5 5 5 5 7.011 5 5 3 1 5 3 5 5 2 2 1 2 7.012 5 5 5 5 5 5 5 5 5 5 5 1 7.014 5 5 4 1 5 3 5 5 4 3 3 1 7.015 5 5 3 2 4 3 5 5 4 3 3 4 7.016 5 5 2 2 2 1 5 5 2 2 2 1 7.017 5 5 5 5 5 5 5 5 5 5 5 4 7.018 5 5 5 5 5 3 5 5 5 5 5 2 7.019 5 5 5 5 5 2 5 5 5 5 5 2 7.021 5 5 5 5 5 4 5 5 5 5 5 4 7.022 5 5 5 4 5 2 5 5 5 5 5 2 7.023 5 5 4 1 4 1 5 5 4 2 2 2 7.027 5 5 5 3 5 2 5 5 3 3 5 1 7.029 5 5 2 3 5 4 5 5 1 2 2 1 7.030 5 5 5 5 5 5 5 5 4 5 5 4 7.031 5 5 5 5 5 5 5 5 5 5 5 5 7.032 5 5 5 3 5 5 5 5 5 4 5 5 7.033 5 5 5 5 5 3 5 5 5 5 5 4 7.034 5 5 3 1 3 2 5 5 1 2 1 1 7.035 5 5 5 5 5 4 5 5 5 5 5 3 7.036 5 5 3 2 4 4 5 5 2 2 1 4 7.038 5 5 3 5 5 5 5 5 3 5 5 4

(150) TABLE-US-00018 TABLE B8 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 8.001 5 5 2 1 5 5 5 5 2 1 5 3

(151) TABLE-US-00019 TABLE B9 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 9.001 4 3 4 4 4 1 1 2 1 3 2 1 9.002 5 4 2 1 2 2 1 1 1 1 1 1 9.003 4 4 2 1 1 2 1 2 1 1 1 1 9.004 4 4 1 1 1 3 1 1 1 1 1 1 9.005 4 2 1 1 1 2 1 1 1 1 1 1 9.006 3 3 2 2 1 2 1 1 1 1 1 1 9.007 4 3 2 1 1 2 1 1 1 1 1 1 9.008 3 3 1 1 1 1 2 2 1 1 4 1 9.009 5 4 3 2 3 3 1 1 1 1 1 1 9.010 5 5 2 2 4 4 1 5 1 1 5 1 9.011 5 5 5 4 5 4 1 4 3 2 5 1 9.016 5 5 3 3 4 2 1 1 1 2 1 1 9.017 4 3 2 2 5 2 1 1 1 2 1 2

(152) TABLE-US-00020 TABLE B10 POST Application PRE Application Compound SOLNI AMARE SETFA ALOMY ECHCG IPOHE SOLNI AMARE SETFA ALOMY ECHCG IPOHE 10.002 5 5 1 1 2 4 1 4 1 1 1 1 10.003 5 5 4 1 5 4 1 5 1 1 1 1 10.004 5 5 3 1 4 4 1 2 1 1 1 1 10.005 5 5 5 2 5 4 5 5 1 1 2 1