HERBICIDAL CINNOLINE DERIVATIVES

Abstract

Compounds of the formula (I), wherein the substituents are as defined in claim 1. The invention further relates to herbicidal compositions which comprise a compound of Formula (I) and to the use of compounds of Formula (I) for controlling weeds, in particular in crops of useful plants.

##STR00001##

Claims

1. A compound of formula (I): ##STR00147## wherein X is O, NR.sup.10 or S; R.sup.r is phenyl optionally substituted with 1, 2, 3, or 4 groups, which may be the same or different, represented by R.sup.7; R.sup.2 is S(O)C.sub.1-C.sub.6alkyl, S(O).sub.nC.sub.1-C.sub.6haloalkyl, or S(O).sub.nC.sub.3-C.sub.6cycloalkyl; n is 0, 1 or 2; R.sup.3 is hydrogen, C.sub.1-C.sub.12alkyl, C.sub.1-C.sub.6haloalkyl, cyanoC.sub.1-C.sub.6alkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.3-C.sub.6cycloalkylC.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxyC.sub.1-C.sub.6alkyl, C.sub.2-C.sub.6alkenyl, C.sub.2-C.sub.6haloalkenyl, C.sub.2-C.sub.6alkynyl, C.sub.1-C.sub.6alkoxycarbonylC.sub.1-C.sub.6alkyl, N,N-di(C.sub.1-C.sub.6alkyl)aminoC.sub.1-C.sub.6alkyl, phenyl, phenylC.sub.1-C.sub.12alkyl, benzyloxyC.sub.1-C.sub.6alkyl, heterocyclyl, wherein the wherein the heterocyclyl moiety is a 4-, 5- or 6-membered non-aromatic monocyclic ring comprising 1 or 2 heteroatoms individually selected from N, O and S, and wherein the phenyl and heterocyclyl moieties may be optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R.sup.1; R.sup.4, R.sup.5, and R.sup.6 are each independently selected from hydrogen, halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.6alkylsulfinyl, and C.sub.1-C.sub.6alkylsulfonyl; R.sup.7 is halogen, cyano, C.sub.1-C.sub.6alkyl, C.sub.1-C.sub.6alkoxy, C.sub.1-C.sub.6haloalkyl, C.sub.1-C.sub.6haloalkoxy, C.sub.1-C.sub.6alkylsulfanyl, C.sub.1-C.sub.6alkylsulfinyl, or C.sub.1-C.sub.6alkylsulfonyl; or any two adjacent R.sup.7 groups together with the carbon atoms to which they are attached, may form a 5- or 6-membered heterocyclyl ring, comprising 1 or 2 heteroatoms selected from O and N, and wherein the heterocyclyl ring may be optionally substituted with 1, 2, 3, or 4 groups, which may be the same or different, represented by R.sup.9; R.sup.8 and R.sup.9 are each independently selected from halogen, C.sub.1-C.sub.3alkyl, and C.sub.1-C.sub.3alkoxy; R.sup.10 is hydrogen, C.sub.1-C.sub.3alkyl, or C.sub.1-C.sub.3alkoxy; or a salt or an N-oxide thereof.

2. The compound according to claim 1, wherein R.sup.r is phenyl optionally substituted with 1 or 2 groups, which may be the same or different, represented by R.sup.7.

3. The compound according to claim 1, wherein R.sup.2 is S(O).sub.nC.sub.1-C.sub.3alkyl, S(O).sub.nC.sub.1-C.sub.3haloalkyl, or S(O).sub.nC.sub.3-C.sub.4cycloalkyl.

4. The compound according to claim 1, wherein R.sup.2 is methylsulfanyl, methylsulfonyl, ethylsulfanyl, ethylsulfonyl, 2,2,2-trifluoroethylsulfanyl, 2,2,2-trifluoroethylsulfonyl, cyclopropylsulfanyl, or cyclopropylsulfonyl.

5. The compound according to claim 1, wherein R.sup.3 is hydrogen, C.sub.1-C.sub.11alkyl, 2-chloroethyl, 2,2-difluoroethyl, 2-cyanoethyl, cyclopropylmethyl, 1-cyclopropylethyl, 3-methoxypropyl, 3-methoxy-3-methylbutyl, allyl, 1-methylallyl, 2-chloroallyl, prop-2-ynyl, but-3-ynyl, pent-4-ynyl, methoxycarbonylmethyl, N,N-di(methyl)aminoethyl, phenylC.sub.3-C.sub.9alkyl, benzyloxybutyl, or heterocyclyl, wherein the wherein the heterocyclyl moiety is a 5- or 6-membered non-aromatic monocyclic ring comprising a single oxygen atom.

6. The compound according to claim 1, wherein R.sup.4, R.sup.5, and R.sup.6 are each independently selected from hydrogen, fluoro, bromo, cyano, methyl, isopropyl, isobutyl, methoxy, and trifluoromethyl.

7. The compound according to claim 1, wherein R.sup.4, R.sup.5, and R.sup.6 are all hydrogen.

8. The compound according to claim 1, wherein R.sup.7 is halogen, cyano, C.sub.1-C.sub.3alkyl, C.sub.1-C.sub.3alkoxy, C.sub.1-C.sub.3haloalkyl, C.sub.1-C.sub.3haloalkoxy, C.sub.1-C.sub.3alkylsulfanyl, C.sub.1-C.sub.3alkylsulfinyl, or C.sub.1-C.sub.3alkylsulfonyl.

9. The compound according to claim 1, wherein R.sup.7 is fluoro, bromo, chloro, cyano, methyl, methoxy, trifluoromethyl, or trifluoromethoxy.

10. The compound according to claim 1, wherein X is O.

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

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

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

14. A method of controlling unwanted plant growth, comprising applying a compound of Formula (I) as defined in claim 1 to the unwanted plants or to the locus thereof.

15. Use of a compound of Formula (I) according to claim 1 as a herbicide.

Description

EXAMPLES

[0177] The following non-limiting examples provide specific synthesis methods for representative compounds of the present invention, as referred to in Table 2 below.

Example 1: Synthesis of 5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid (Compound P2)

[0178] ##STR00027##

Step 1: Synthesis of ethyl 3-(2,6-difluorophenyl)-3-oxo-propanoate

##STR00028##

[0179] To a solution of potassium;3-ethoxy-3-oxo-propanoic acid (6.11 g, 35.7 mmol) in acetonitrile (66 mL) at 0° C. and under nitrogen was added triethylamine (3.78 g, 37.4 mmol) and dichloromagnesium (4.1 g, 42.5 mmol). The reaction mixture was stirred at room temperature for 3.5 hours. The reaction mixture was cooled to 0° C. and 2,6-difluorobenzoyl chloride (3.0 g, 17 mmol) was added portionwise. The reaction mixture was stirred for 1.5 hours in ice and then at room temperature for 2 hours before standing for 18 hours. The reaction mixture was evaporated under reduced pressure and azeotroped with toluene. The residue was suspended in ethyl acetate (50 mL) and 2M aqueous hydrochloric acid. The phases were separated and the aqueous was re-extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulfate and evaporated to dryness under reduced pressure to give the crude desired product (mixture of tautomers) as a pale-yellow liquid (4.5 g, 20 mmol). 1 H NMR (400 MHz, chloroform) 6=7.53-7.37 (m, 1H), 7.04-6.88 (m, 2H), 4.30-4.22 (m, 2H), 3.47-3.38 (m, 2H), 1.34-1.28 (m, 3H) (data for keto form only).

Step 2: Synthesis of ethyl (2E)-3-(2,6-difluorophenyl)-3-oxo-2-[[4-(trifluoromethoxy)phenyl]hydrazono]propanoate

##STR00029##

[0180] To a solution of 4-(trifluoromethoxy)aniline (1.10 g, 6.25 mmol) in hydrochloric acid (5.2 mL, 31 mmol) at 0° C. was added a solution of sodium nitrite (0.48 g, 6.87 mmol) in water (1.3 mL). The reaction mixture was stirred for 30 mins at 0° C. before being added portionwise to a suspension of ethyl 3-(2,6-difluorophenyl)-3-oxo-propanoate (2.03 g, 6.25 mmol) and potassium acetate (3.1 g, 31.2 mmol) in water (1.2 mL). The reaction mixture was stirred for 2.75 hours before the solution was decanted to leave a red gum. This was dissolved in ethyl acetate, dried over magnesium sulfate, and evaporated to dryness under reduced pressure to give the desired product as a red solid (2.6 g, 6.25 mmol, 64%). .sup.1H NMR (400 MHz, chloroform) 6=7.45-7.41 (m, 3H), 7.18-7.11 (m, 2H), 7.05-7.00 (m, 2H), 4.49-4.35 (m, 2H), 1.50-1.35 (m, 3H)

Step 3: Synthesis of ethyl 5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate

##STR00030##

[0181] To a solution of ethyl (2Z)-3-(2,6-difluorophenyl)-3-oxo-2-[[4-(trifluoromethoxy)phenyl]hydrazono] propanoate (2.16 g, 5.179 mmol) in N,N-dimethylformamide (10 mL) was added potassium carbonate (0.58 g, 5.697 mmol). The reaction was mixture heated at 100° C. for 3.5 hours. The cooled reaction mixture was diluted with water and extracted twice into diethyl ether. The combined organic extracts were dried over magnesium sulfate and evaporated to dryness under reduced pressure to give a red solid. Trituration with cyclohexane gave the desired product as an off-white solid (1.2 g, 3.02 mmol, 58%). .sup.1H NMR (500 MHz, chloroform) 6=7.61-7.54 (m, 3H), 7.50-7.38 (m, 2H), 7.15-7.04 (m, 1H), 6.97-6.88 (m, 1H), 4.50-4.30 (m, 2H), 1.43-1.33 (m, 3H)

Step 4: Synthesis of 5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid

##STR00031##

[0182] To a solution of ethyl 5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (0.71 g, 1.8 mmol) in tetrahydrofuran (10 mL) was added a solution of lithium;hydroxide;hydrate (0.31 g, 7.19 mmol) in water (1.8 mL). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was acidified by the addition of 2M aqueous hydrochloric acid and the precipitated solid was collected by filtration and air-dried to give the desired product as an off-white powder (0.65 g, 1.76 mmol, 98%). .sup.1H NMR (400 MHz, chloroform) 6=7.82-7.73 (m, 1H), 7.63-7.56 (m, 2H), 7.52-7.46 (m, 2H), 7.36-7.30 (m, 1H), 7.17-7.12 (m, 1H)

Step 5: Synthesis of 5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid

##STR00032##

[0183] To a solution of 5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid (0.40 g, 1.1 mmol) in N,N-dimethylformamide (5 mL) was added sodium methanesulfinate (0.34 g, 3.26 mmol). The reaction mixture was heated at 80° C. for 5 hours. The cooled reaction mixture was poured onto ice upon which a yellow solid crashed out of solution. The solid was collected by filtration to give the desired product as a pale-yellow powder (0.37 g, 0.85 mmol, 78%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ=8.34-8.25 (m, 1H), 8.00-7.90 (m, 1H), 7.88-7.83 (m, 2H), 7.75-7.66 (m, 2H), 7.59-7.52 (m, 1H), 3.72-3.63 (m, 3H)

Example 2: Synthesis of 5-methylsulfanyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid (Compound P1)

[0184] ##STR00033##

[0185] To a solution of 5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid (0.20 g, 0.53 mmol) in N,N-dimethylformamide (2 mL) at room temperature was added sodium thiomethoxide (0.11 g, 1.6 mmol). The reaction mixture was heated under microwave irradiation at 100° C. for 1 hour. The reaction mixture was diluted with 2M aqueous hydrochloric acid and the precipitated solid was collected by filtration and washed with water to give the desired product as a yellow powder (0.16 g, 0.40 mmol, 75%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ=7.88-7.78 (m, 2H), 7.75-7.59 (m, 3H), 7.37-7.31 (m, 1H), 6.87-6.81 (m, 1H), 2.49-2.43 (m, 3H)

Example 3: Synthesis of methyl 5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (Compound P3)

[0186] ##STR00034##

[0187] To a suspension of 5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid (0.20 g, 0.47 mmol) in methanol (10 mL) was added concentrated sulfuric acid (0.003 mL, 0.047 mmol). The reaction mixture was heated at 80° C. for 2 hours. On cooling, a pale solid precipitated out of solution. The solid was collected by filtration, washed with water, and air-dried to give the desired product as an off-white powder (0.18 g, 0.40 mmol, 87%). .sup.1H NMR (400 MHz, chloroform) 6=8.49-8.38 (m, 1H), 7.83-7.71 (m, 1H), 7.58-7.53 (m, 2H), 7.51-7.47 (m, 3H), 4.00-3.95 (m, 3H), 3.77-3.66 (m, 3H)

Example 4: Synthesis of 1-(4-chlorophenyl)-5-methylsulfonyl-4-oxo-cinnoline-3-carboxylic acid (Compound P5)

[0188] ##STR00035##

Step 1: Synthesis of ethyl (2E)-2-[(4-chlorophenyl)hydrazono]-3-(2,6-difluorophenyl)-3-oxo-propanoate

##STR00036##

[0189] Prepared as for ethyl (2E)-3-(2,6-difluorophenyl)-3-oxo-2-[[4-(trifluoromethoxy)phenyl]hydrazono] propanoate (example 1; step 2) using 4-chloroaniline (1.17 g, 9.2 mmol). After a reaction time of 2.75 hours, the solid was collected by filtration to give the desired product as a yellow solid (2.2 g, 5.9 mmol, 64%). .sup.1H NMR (400 MHz, chloroform) 6=13.15-13.05 (m, 1H), 7.44-7.32 (m, 1H), 7.27-7.23 (m, 3H), 7.00-6.91 (m, 3H), 4.49-4.38 (m, 2H), 1.51-1.39 (m, 3H)

Step 2: Synthesis of ethyl 1-(4-chlorophenyl)-5-fluoro-4-oxo-cinnoline-3-carboxylate

##STR00037##

[0190] Prepared as for ethyl 5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (example 1; step 3) using ethyl (2Z)-2-[(4-chlorophenyl)hydrazono]-3-(2,6-difluorophenyl)-3-oxo-propanoate (2.2 g, 5.9 mmol). On completion of reaction, the cooled reaction mixture was poured onto ice and the precipitated solid was collected by filtration to give the desired product as a yellow powder (1.8 g, 5.3 mmol, 89%). .sup.1H NMR (400 MHz, chloroform) 6=7.60-7.52 (m, 3H), 7.48-7.40 (m, 2H), 7.14-7.07 (m, 1H), 7.00-6.87 (m, 1H), 4.51-4.40 (m, 2H), 1.45-1.34 (m, 3H)

Step 3: Synthesis of 1-(4-chlorophenyl)-5-fluoro-4-oxo-cinnoline-3-carboxylic acid

##STR00038##

[0191] Prepared as for 5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid (example 1; step 4) using ethyl 1-(4-chlorophenyl)-5-fluoro-4-oxo-cinnoline-3-carboxylate (1.29 g, 3.7 mmol) to give the desired product as an off-white solid (1.15 g, 3.6 mmol, 97%). .sup.1H NMR (500 MHz, chloroform) 6=14.22-13.90 (m, 1H), 7.82-7.74 (m, 1H), 7.63-7.59 (m, 2H), 7.51-7.37 (m, 2H), 7.36-7.26 (m, 1H), 7.19-7.00 (m, 1H)

Step 4: Synthesis of 1-(4-chlorophenyl)-5-methylsulfonyl-4-oxo-cinnoline-3-carboxylic acid

##STR00039##

[0192] To a solution of 1-(4-chlorophenyl)-5-fluoro-4-oxo-cinnoline-3-carboxylic acid (0.20 g, 0.63 mmol) in N,N-dimethylformamide (2 mL) was added sodium methanesulfinate (0.19 g, 1.9 mmol). The reaction mixture was heated under microwave irradiation at 80° C. for 45+45 minutes. The cooled reaction mixture was poured onto ice and the precipitated solid was collected by filtration to give a pale-yellow powder which was triturated with dichloromethane. Addition of dimethyl sulfoxide/methanol mixture (9:1) resulted in precipitation of a white solid which was collected by filtration to give the desired product as a white solid (0.071 g, 0.19 mmol, 30%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ=8.36-8.27 (m, 1H), 7.99-7.91 (m, 1H), 7.82-7.68 (m, 4H), 7.61-7.46 (m, 1H), 3.73-3.65 (m, 3H)

Example 5: Synthesis of 1-(4-chlorophenyl)-5-methylsulfanyl-4-oxo-cinnoline-3-carboxylic acid

[0193] ##STR00040##

[0194] A solution of 1-(4-chlorophenyl)-5-fluoro-4-oxo-cinnoline-3-carboxylic acid (0.20 g, 0.63 mmol) and sodium thiomethoxide (0.13 g, 1.9 mmol) in N,N-dimethylformamide (2 mL) was heated under microwave irradiation at 80° C. for 60+60 minutes. The cooled reaction mixture was diluted with 2M aqueous hydrochloric acid resulting in precipitation of a yellow solid which was insoluble upon extraction into either ethyl acetate or dichloromethane. The solids were collected by filtration from the aqueous phase to give the desired product as a bright yellow powder (0.048 g, 0.14 mmol, 22%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ=7.78-7.75 (m, 2H), 7.72-7.64 (m, 3H), 7.38-7.30 (m, 1H), 6.88-6.84 (m, 1H), 2.48-2.44 (m, 3H).

Example 6: Synthesis of 6-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy) phenyl]cinnoline-3-carboxylic acid (Compound P6)

[0195] Step 1: Synthesis of ethyl 3-(3-bromo-2,6-difluoro-phenyl)-3-oxo-propanoate

##STR00041##

To a solution of 3-bromo-2,6-difluoro-benzoic acid (18 g, 76.0 mmol) in tetrahydrofuran (1.85 mmol) at 0° C. was added 1,1′-carbonyldiimidazole (83.5 mmol) portionwise. The reaction mixture was warmed to room temperature and stirred for 1 hour. The reaction mixture was then added dropwise into a suspension of magnesium chloride (114.0 mmol) and ethyl potassium malonate (114.0 mmol) in tetrahydrofuran (1860 mmol). The reaction mixture was heated at 50° C. for 5 hours. The cooled reaction mixture quenched with 2M aqueous hydrochloric acid and extracted into ethyl acetate (3×100 mL). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution then brine, dried over sodium sulfate and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0-15% ethyl acetate in cyclohexane as eluent to give desired product as a mixture of keto-enol isomers (15 g).
Step 2: Synthesis of ethyl (2E)-3-(3-bromo-2,6-difluoro-phenyl)-3-oxo-2-[[4-(trifluoromethoxy) phenyl]hydrazono]propanoate

##STR00042##

[0196] To a cooled (0° C.) mixture of 4-(trifluoromethoxy)aniline (52.3 mmol) in 6M aqueous hydrochloric acid (261 mmol) was added dropwise over 10 minutes a solution of sodium nitrite (57.5 mmol) in water (2 mL/mmol). This was stirred at 0° C. for 60 minutes before being added dropwise over 10 minutes to a cooled (0° C.) solution of ethyl 3-(3-bromo-2,6-difluoro-phenyl)-3-oxo-propanoate (15.0 g, 48.8 mmol) and potassium acetate (244.2 mmol) in methanol (2 mL/mmol) and water (48.8 mmol, 5 mol/L). The reaction mixture was stirred at room temperature for 2 hours after which the reaction mixture was diluted with water (100 mL) and extracted into tert-butyl methyl ether (3×250 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure to give desired product as a yellow solid (22 g).

Step 3: Synthesis of ethyl 6-bromo-5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl] cinnoline-3-carboxylate (and ethyl 8-bromo-5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl] cinnoline-3-carboxylate)

##STR00043##

To a solution of ethyl (2Z)-3-(3-bromo-2,6-difluoro-phenyl)-3-oxo-2-[[4-(trifluoromethoxy)phenyl]hydrazono]propanoate (8.0 g, 16.2 mmol) in tetrahydrofuran (160 mL) at 0° C. and under nitrogen was added portionwise a 60% suspension of sodium hydride in mineral oil (24.2 mmol). The reaction mixture was stirred at 0° C. for 4 hours. The reaction mixture was quenched by addition of ice-cold water, acidified with 1 M aqueous hydrochloric acid and extracted into ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using ethyl acetate in cyclohexane as eluent to give desired product isomer (5.1 g). .sup.1H NMR (400 MHz, CDCl.sub.3): 1.41 (t, 3H), 4.45 (q, 2H), 6.88 (dd, 1H), 7.49-7.44 (m, 2H), 7.58-7.53 (m, 2H), 7.74 (dd, 1H) Step 4: Synthesis of ethyl 6-bromo-5-methylsulfanyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (and ethyl 5,6-bis(methylsulfanyl)-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate)

##STR00044##

[0197] To a solution of ethyl 6-bromo-5-fluoro-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (2.5 g, 5.3 mmol) in N,N-dimethylformamide (7 mL/g) at room temperature and under nitrogen was added sodium;methanethiol (1.2 equiv., 6.3 mmol). The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was quenched by addition of water (200 mL), acidified with 1M aqueous hydrochloric acid and extracted into ethyl acetate (3×300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0 to 20% ethyl acetate in cyclohexane as eluent to give desired product as a yellow solid (2.0 g).

Step 5: Synthesis of ethyl 6-bromo-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate

##STR00045##

To a solution of ethyl 6-bromo-5-methylsulfanyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (5.4 g, 11 mmol) in trifluoromethylbenzene (10 mL/mmol) at room temperature and under nitrogen was added 3-chloroperoxybenzoic acid (24 mmol, 70 mass). The reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with water (200 mL) and extracted into ethyl acetate (3×200 mL). The combined organic extracts were washed with saturated bicarbonate solution (3×100 mL) and brine (200 mL) then dried over sodium sulphate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using ethyl acetate in cyclohexane as eluent to give desired product (4.6 g). .sup.1H NMR (400 MHz, CDCl.sub.3): 1.40 (t, 3H), 3.76 (s, 3H), 4.46 (q, 2H), 7.16 (d, 1H), 7.38-7.63 (m, 4H), 7.82 (d, 1H)
Step 6: Synthesis of ethyl 6-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate

##STR00046##

To a solution of ethyl 6-bromo-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (500 mg, 0.934 mmol) in diethylene dioxide (30 mL/g) was added sequentially 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (2.34 mmol), sodium carbonate (1.87 mmol) and water (1 mL/g) and the resultant reaction mixture was degassed by bubbling through nitrogen for 10 minutes. The PdCI2(dppf).DCM (0.140 mmol) was added and the reaction mixture was heated at 85° C. for 20 hours. The reaction mixture was poured onto ice and diluted with water (100 mL) then acidified with 1M aqueous hydrochloric acid and extracted into ethyl acetate (3×50 mL). The combined organic extracts were washed with brine (100 mL), dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0 to 20% ethyl acetate in cyclohexane as eluent to give desired product (0.230 g). .sup.1H NMR (400 MHz, CDCl.sub.3): 1.40 (t, 3H), 2.82 (s, 3H), 3.77 (s, 3H), 4.46 (q, 2H), 7.24 (d, 1H), 7.44-7.49 (m, 3H), 7.50-7.56 (m, 2H)
Step 7: Synthesis of 6-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid

##STR00047##

To a solution of ethyl 6-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (180 mg, 0.383 mmol) in tetrahydrofuran (15 mL/g) was added a solution of lithium hydroxide hydrate (1.53 mmol) in water (2 mL/g). The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water (100 mL) and washed with ethyl acetate. The aqueous phase was acidified by addition of 1 M aqueous hydrochloric acid and then extracted into ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure to give desired product as a white solid (0.150 g). .sup.1H NMR (400 MHz, DMSO-d6): 2.73 (s, 3H), 3.75 (s, 3H), 7.34 (d, 1H), 7.69 (d, 3H), 7.85 (d, 2H), 13.48-13.71 (brs, 1H)

Example 7: Synthesis of 7-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid (Compound P7)

[0198] Step 1: Synthesis of 4-bromo-2-fluoro-6-methylsulfanyl-benzoic acid

##STR00048##

To a solution of 4-bromo-2,6-difluoro-benzoic acid (1.0 g, 4.22 mmol) in tetrahydrofuran (10 mL/g) at 0° C. was added lithium bis(trimethylsilyl)azanide (4.64 mmol,). The reaction mixture was stirred at 0° C. for 20 minutes before addition of sodium methanethiol (4.64 mmol). The resultant mixture was heated at 80° C. for 3 hours. The cooled reaction mixture was acidified by addition of 1M aqueous hydrochloric acid and diluted with ethyl acetate and water. The organic phase was washed with brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure to give desired product. .sup.1H NMR (400 MHz, CDCl.sub.3): 2.48-2.51 (m, 3H), 7.08-7.18 (m, 1H), 7.19 (s, 1H) Step 2: Synthesis of ethyl 3-(4-bromo-2-fluoro-6-methylsulfanyl-phenyl)-3-oxo-propanoate

##STR00049##

To a solution of 4-bromo-2-fluoro-6-methylsulfanyl-benzoic acid (1.1 g) in tetrahydrofuran (100 mmol) at 0° C. was added portionwise 1,1′-carbonyldiimidazole (5.0 mmol). The reaction mixture was warmed to room temperature and stirred for 1 hour. The reaction mixture was then added to a suspension of magnesium chloride (6.2 mmol) and ethyl potassium malonate (6.2 mmol) in tetrahydrofuran (100 mmol). The reaction mixture was heated at 50° C. for 18 hours. The cooled reaction mixture was quenched by addition of 2M aqueous hydrochloric acid and extracted into ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate solution then dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 15 to 20% ethyl acetate in cyclohexane as eluent to give desired product as a colourless liquid.
Step 3: Synthesis of ethyl (2E)-3-(4-bromo-2-fluoro-6-methylsulfanyl-phenyl)-3-oxo-2-[[4-(trifluoromethoxy)phenyl]hydrazono]propanoate

##STR00050##

To 6M aqueous hydrochloric acid (20.9 mmol) was added 4-(trifluoromethoxy)aniline (4.18 mmol). The resultant mixture was cooled to 0° C. and in an ice bath and to it was added dropwise a solution of sodium nitrite (4.60 mmol) in water (2 mL/mmol). The resultant mixture was stirred at 0° C. for 30 minutes before being added dropwise over 10 minutes to a solution of ethyl 3-(4-bromo-2-fluoro-6-methylsulfanyl-phenyl)-3-oxo-propanoate (1.0 g) and potassium acetate (14.9 mmol) in methanol (2.0 mL/mmol) and water (2.98 mmol) at 0° C. On completion of addition, the reaction mixture was stirred at room temperature for 2 hours. The gummy brownish mass formed was extracted into ethyl acetate, washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure to afford crude desired product.
Step 4: Synthesis of ethyl 7-bromo-5-methylsulfanyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate

##STR00051##

To a solution of ethyl (2Z)-3-(4-bromo-2-fluoro-6-methylsulfanyl-phenyl)-3-oxo-2-[[4-(trifluoromethoxy)phenyl]hydrazono]propanoate (900 mg) in N,N-dimethylformamide (10 mL) was added potassium carbonate (1.89 mmol). The reaction mixture was heated at 100° C. for 2.5 hours. To the cooled reaction mixture was added cold water and the precipitated solid was collected by filtration and air-dried to give the desired product. .sup.1H NMR (400 MHz, DMSO-d6): 1.22-1.30 (m, 3H), 2.45-2.47 (m, 3H), 4.30 (d, 2H), 6.82 (d, 1H), 7.30 (d, 1H), 7.67 (d, 2H), 7.83 (d, 2H)
Step 5: Synthesis of ethyl 7-bromo-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate

##STR00052##

To a solution of ethyl 7-bromo-5-methylsulfanyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (650 mg) in acetonitrile (20 mL) at 0° C. was added 3-chlorobenzenecarboperoxoic acid (2.84 mmol, 70 mass %). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was quenched by addition of saturated aqueous potassium carbonate solution (20 mL) and water (20 mL) and then extracted into ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 40 to 50% ethyl acetate in cyclohexane as eluent to give desired product. .sup.1H NMR (400 MHz, DMSO-d.sub.6): 1.23-1.33 (m, 3H), 3.70 (s, 3H), 4.34 (q, 2H), 7.63 (d, 1H), 7.69 (d, 2H), 7.82-7.90 (m, 2H), 8.25 (d, 1H)
Step 6: Synthesis of ethyl 7-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate

##STR00053##

To a solution of ethyl 7-bromo-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (500 mg) in diethylene dioxide (30 mL/g) was added sequentially 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (2.34 mmol), sodium carbonate (1.87 mmol) and water (1 mL/g). The reaction mixture was degassed by bubbling through with nitrogen for 15 minutes. PdCI2(dppf).DCM (0.14 mmol) was added and the reaction mixture was heated at 100° C. for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with water then brine, then dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 40 to 50% ethyl acetate in cyclohexane as eluent to give desired product. .sup.1H NMR (400 MHz, CDCl.sub.3): 7.56-7.50 (m, 2H), 7.49-7.44 (m, 3H), 7.24 (d, 1H), 4.46 (q, 2H), 3.77 (s, 3H), 2.82 (s, 3H), 1.40 (t, 3H)
Step 7: Synthesis of 7-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylic acid

##STR00054##

To a solution of ethyl 7-methyl-5-methylsulfonyl-4-oxo-1-[4-(trifluoromethoxy)phenyl]cinnoline-3-carboxylate (200 mg) in tetrahydrofuran (10 mL) was added a suspension of lithium hydroxide hydrate (3 equiv., 1.276 mmol) in water (1 mL/g). The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was acidified by the addition of 2M aqueous hydrochloric acid and diluted with additional water. The precipitated solid was collected by filtration, washed with tert-butyl methyl ether and air-dried to give the desired product. .sup.1H NMR (400 MHz, DMSO-d6): 14.26-13.44 (m, 1H), 8.16-8.14 (m, 1H), 7.70 (d, 2H), 7.84 (d, 2H), 7.35 (s, 1H), 3.67 (s, 3H), 2.49-2.47 (m, 3H)

TABLE-US-00010 TABLE 2 .sup.1H NMR and LC/MS data for selected compounds of Table 1 Cpd Compound No. Name Structure & .sup.1H NMR Data LC/MS P1 5-methylsulfanyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00055] R.sub.t = 1.03 min; MS: m/z = 397 (M + H) P2 5-methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00056] R.sub.t = 0.76 min; MS: m/z = 429 (M + H) P3 methyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00057] R.sub.t = 0.90 min; MS: m/z = 443 (M + H) P4 1-(4-chlorophenyl)-5- methylsulfanyl-4-oxo- cinnoline-3-carboxylic acid [00058] R.sub.t = 0.94 min; MS: m/z = 347 (M + H) P5 1-(4-chlorophenyl)-5- methylsulfonyl-4-oxo- cinnoline-3-carboxylic acid [00059] R.sub.t = 0.64 min; MS: m/z = 379 (M + H) P6 6-methyl-5-methylsulfonyl-4- oxo-1-[4-(trifluoromethoxy) phenyl]cinnoline-3- carboxylic acid [00060] P7 7-methyl-5-methylsulfonyl-4- oxo-1-[4-(trifluoromethoxy) phenyl]cinnoline-3- carboxylic acid [00061] P8 ethyl 6-methyl-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00062] P9 ethyl 7-methyl-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00063] P10 ethyl 6-bromo-5- methysulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00064] P11 ethyl 7-bromo-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00065] P12 6-bromo-5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00066] P13 7-bromo-5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00067] P14 7-isobutyl-5-methylsulfonyl- 4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00068] P15 6-isobutyl-5-methylsulfonyl- 4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00069] P16 6-cyano-5-methysulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00070] P17 7-cyano-5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00071] P18 6-methoxy-5-methylsulfonyl- 4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00072] P19 7-methoxy-5-methylsulfonyl- 4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00073] P20 6-fluoro-5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00074] P21 7-fluoro-5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00075] P22 ethyl 5-ethylsulfonyl-4-oxo- 1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00076] P23 ethyl 5-ethylsulfanyl-4-oxo- 1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00077] P24 ethyl 5-ethylsulfinyl-4-oxo-1- [4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00078] P25 5-ethylsulfinyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00079] P26 5-ethylsulfanyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00080] P27 5-ethylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00081] P28 ethyl 5-methylsulfinyl-4-oxo- 1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00082] P29 5-cyclopropylsulfonyl-4-oxo- 1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00083] P30 5-cyclopropylsulfanyl-4-oxo- 1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00084] P31 5-cyclopropylsulfinyl-4-oxo- 1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00085] P32 ethyl 5-cyclopropylsulfinyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00086] P33 ethyl 5-cyclopropylsulfanyl- 4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00087] P34 ethyl 5-cyclopropylsulfonyl- 4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00088] P35 4-oxo-5-(2,2,2- trifluoroethylsulfonyl)-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00089] P36 4-oxo-5-(2,2,2- trifluoroethylsulfanyl)-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00090] P37 4-oxo-5-(2,2,2- trifluoroethylsulfinyl)-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00091] P38 ethyl 4-oxo-5-(2,2,2- trifluoroethylsulfinyl)-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00092] P39 ethyl 4-oxo-5-(2,2,2- trifluoroethylsulfanyl)-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00093] P40 ethyl 4-oxo-5-(2,2,2- trifluoroethylsulfonyl)-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00094] P41 1-(4-chloro-2-fluoro-phenyl)- 5-methylsulfonyl-4-oxo- cinnoline-3-carboxylic acid [00095] P42 ethyl 1-(4-chloro-2-fluoro- phenyl)-5-methylsulfonyl-4- oxo-cinnoline-3-carboxylate [00096] P43 1-(2,4-dichlorophenyl)-5- methylsulfonyl-4-oxo- cinnoline-3-carboxylic acid [00097] P44 ethyl 1-(2,4-dichlorophenyl)- 5-methylsulfonyl-4-oxo- cinnoline-3-carboxylate [00098] P45 ethyl 6-isobutyl-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00099] P46 ethyl 7-isobutyl-5- methysulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00100] P47 ethyl 6-cyano-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00101] P48 ethyl 7-cyano-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00102] P49 ethyl 6-methoxy-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00103] P50 ethyl 7-methoxy-5- methysulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00104] P51 ethyl 6-fluoro-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00105] P52 ethyl 7-fluoro-5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00106] P53 ethyl 6-bromo-5- methylsulfanyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00107] P54 ethyl 7-fluoro-5- methylsulfanyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00108] P55 ethyl 7-cyano-5- methylsulfanyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00109] P56 methyl 7-methoxy-5- methylsulfanyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00110] P57 ethyl 7-methoxy-5- methylsulfanyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00111] P58 7-cyano-5-methylsulfanyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylic acid [00112] P59 hexyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- oline-3-carboxylate [00113] P60 undecyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00114] R.sub.t = 3.31 min; MS: m/z = 583 (M + H) P61 2-chloroethyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00115] R.sub.t = 2.27 min; MS: m/z = 491 (M + H) P62 pent-4-ynyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00116] R.sub.t = 2.35 min; MS: m/z = 495 (M + H) P63 cyclopropylmethyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00117] R.sub.t = 2.37 min; MS: m/z = 483 (M + H) P64 1-methylallyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00118] R.sub.t = 2.41 min; MS: m/z = 483 (M + H) P65 isopropyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00119] R.sub.t = 2.35 min; MS: m/z = 471 (M + H) P66 2-chloroallyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00120] R.sub.t = 2.41 min; MS: m/z = 503 (M + H) P67 2,2-difluoroethyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00121] R.sub.t = 2.23 min; MS: m/z = 493 (M + H) P68 2,2-dimethylpropyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00122] R.sub.t = 2.61 min; MS: m/z = 499 (M + H) P69 3-methoxypropyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00123] R.sub.t = 2.22 min; MS: m/z = 501 (M + H) P70 tetrahydrofuran-3-yl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00124] R.sub.t = 2.11 min; MS: m/z = 499 (M + H) P71 but-3-ynyl 5-methylsulfonyl- 4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00125] R.sub.t = 2.25 min; MS: m/z = 481 (M + H) P72 isobutyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00126] R.sub.t = 2.50 min; MS: m/z = 485 (M + H) P73 2-cyanoethyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00127] R.sub.t = 2.06 min; MS: m/z = 482 (M + H) P74 1-cyclopropylethyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00128] R.sub.t = 2.48 min; MS: m/z = 497 (M + H) P75 penyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00129] R.sub.t = 2.62 min; MS: m/z = 499 (M + H) P76 2-(dimethylamino)ethyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00130] R.sub.t = 1.61 min; MS: m/z = 500 (M + H) P77 heptyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00131] R.sub.t = 2.86 min; MS: m/z = 527 (M + H) P78 prop-2-ynyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00132] R.sub.t = 2.72 min; MS: m/z = 525 (M + H) P79 prop-2-ynyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00133] R.sub.t = 2.19 min; MS: m/z = 467 (M + H) P80 allyl 5-methylsulfonyl-4-oxo- 1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00134] R.sub.t = 2.3 min; MS: m/z = 469 (M + H) P81 (2-methoxy-2-oxo-ethyl) 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00135] R.sub.t = 2.12 min; MS: m/z = 501 (M + H) P82 nonyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00136] R.sub.t = 3.09 min; MS: m/z = 555 (M + H) P83 9-phenylnonyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00137] R.sub.t = 3.22 min; MS: m/z = 630 (M + H) P84 3-phenylpropyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00138] R.sub.t = 2.65 min; MS: m/z = 547 (M + H) P85 (3-methoxy-3-methyl-butyl) 5-methysulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00139] R.sub.t = 2.38 min; MS: m/z = 551 (M + H) P86 3,3-dimethylbutyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00140] R.sub.t = 2.70 min; MS: m/z = 513 (M + H) P87 2-cyclohexylethyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00141] R.sub.t = 2.88 min; MS: m/z = 539 (M + H) P88 isopentyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00142] R.sub.t = 2.61 min; MS: m/z = 499 (M + H) P89 4-benzyloxybutyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carboxylate [00143] R.sub.t = 2.66 min; MS: m/z = 591 (M + H) P90 S-octyl 5-methylsulfonyl-4- oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carbothioate [00144] R.sub.t = 3.12 min; MS: m/z = 557 (M + H) P91 S-isopentyl 5- methylsulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carbothioate [00145] R.sub.t = 2.76 min; MS: m/z = 515 (M + H) P92 S-(3-phenylpropyl) 5- methyslulfonyl-4-oxo-1-[4- (trifluoromethoxy)phenyl]cin- noline-3-carbothioate [00146] R.sub.t = 2.77 min; MS: m/z = 563 (M + H)

Biological Examples

[0199] Seeds of a variety of test species are sown in standard soil in pots (Amaranthus retoflexus (AMARE), Solanum nigrum (SOLNI), Setaria faberi (SETFA), Lolium perenne (LOLPE), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE), Abutilon theophrasti (ABUTH), Zea mays (ZEAMX)). After 8 days cultivation under controlled conditions in a glasshouse (at 24° C./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/ha unless otherwise stated. The test plants are then grown in a glasshouse under controlled conditions in a glasshouse (at 24° C./16° C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days the test is evaluated for the percentage damage caused to the plant. The biological activities are shown in the following table on a five-point scale (5=81-100%; 4=61-80%; 3=41-60%; 2=21-40%; 1=10-20%; 0=0%;−=not tested).

TABLE-US-00011 TABLE B1 Pre-emergence Test Compound AMARE SOLNI SETFA LOLPE ECHCG IPOHE ABUTH ZEAMX P1 0 0 0 0 0 0 — — P2 1 4 5 5 5 1 — — P3 1 1 4 4 4 1 — — P4 0 0 0 0 0 0 — — P5 1 1 4 4 4 1 — — P6 1 — 4 — 3 1 2 1 P7 1 — 4 — 4 1 1 1 P8 1 — 4 — 3 1 1 1 P9 1 — 4 — 4 1 1 1 P10 1 — 1 — 0 0 1 0 P11 0 — 0 — 0 0 0 0 P12 0 — 4 — 1 0 1 0 P13 0 — 0 — 0 0 1 0 P14 1 — 1 — 1 0 1 1 P15 1 — 1 — 1 0 1 0 P18 0 — 0 — 1 0 0 1 P19 1 — 5 — 2 0 0 0 P20 0 — 0 — 0 0 0 0 P21 0 — 4 — 2 0 0 1 P22 0 — 0 — 0 0 0 0 P23 0 — 0 — 0 0 0 1 P24 0 — 0 — 0 0 0 0 P25 0 — 1 — 0 0 0 0 P26 1 — 0 — 0 0 0 0 P27 0 — 3 — 0 0 0 1 P28 0 — 0 — 0 0 0 0 P29 0 — 0 — 0 0 0 0 P30 0 — 0 — 0 0 0 0 P31 0 — 0 — 0 0 0 0 P32 0 — 2 — 1 0 0 0 P33 0 — 2 — 1 0 0 0 P34 0 — 0 — 0 0 0 0 P35 0 — 0 — 0 0 1 1 P37 0 — 0 — 0 0 1 0 P38 0 — 0 — 0 0 0 0 P39 1 — 0 — 0 0 0 0 P40 0 — 1 — 0 0 1 1 P41 1 — 4 — 2 1 1 1 P42 0 — 4 — 3 1 1 0 P43 0 — 4 — 2 1 0 0 P44 1 — 4 — 2 0 0 0 P45 0 — 0 — 0 0 0 0 P46 0 — 0 — 0 0 1 2 P47 0 — 0 — 0 0 0 0 P48 0 — 0 — 0 0 0 0 P49 0 — 0 — 0 0 0 0 P50 0 — 4 — 1 0 0 0 P51 0 — 0 — 0 0 0 0 P52 1 — 4 — 3 0 1 0 P53 1 — 1 — 1 0 1 — P54 1 — 2 — 2 0 1 0 P55 0 — 0 — 0 0 1 0 P56 0 — 0 — 0 0 0 0 P57 0 — 0 — 0 0 0 0 P59 2 — 4 — 3 2 3 3 P60 1 — 4 — 1 0 1 1 P61 0 — 5 — 4 0 0 1 P62 0 — 5 — 4 0 0 0 P63 0 — 5 — 3 0 0 0 P64 0 — 5 — 4 0 0 0 P65 1 — 4 — 4 0 1 0 P66 0 — 5 — 4 1 0 1 P67 0 — 5 — 4 0 0 2 P68 0 — 4 — 4 0 0 0 P69 0 — 4 — 4 0 0 0 P70 0 — 4 — 3 0 0 1 P71 0 — 5 — 4 0 0 0 P72 0 — 4 — 4 0 0 0 P73 0 — 5 — 3 0 0 0 P74 0 — 5 — 4 0 0 0 P75 0 — 4 — 4 0 0 1 P76 0 — 4 — 3 0 1 0 P77 0 — 5 — 3 0 0 0 P78 0 — 5 — 4 0 0 0 P79 0 — 5 — 5 1 0 1 P80 0 — 5 — 4 0 0 1 P81 0 — 5 — 4 0 0 0 P82 0 — 3 — 1 0 0 0 P83 0 — 0 — 0 0 0 0 P84 0 — 4 — 3 0 0 0 P85 0 — 4 — 4 0 0 0 P86 0 — 4 — 5 0 1 1 P87 0 — 3 — 1 1 1 1 P88 0 — 5 — 4 0 0 0 P89 0 — 4 — 4 0 0 0 P90 0 — 4 — 3 0 0 0 P91 0 — 4 — 3 0 0 0 P92 1 — 3 — 1 0 1 0

TABLE-US-00012 TABLE B2 Post-emergence Test Cpd No. AMARE SOLNI SETFA LOLPE ECHCG IPOHE ABUTH ZEAMX P1 0 0 0 0 0 0 — — P2 1 4 4 4 4 2 — — P3 1 1 4 4 4 1 — — P4 0 0 0 0 0 0 — — P5 1 4 4 4 4 1 — — P6 2 — 3 — 4 1 1 1 P7 1 — 4 — 4 2 1 2 P8 1 — 4 — 4 1 1 1 P9 1 — 3 — 4 1 1 1 P10 1 — 1 — 1 0 1 1 P11 0 — 1 — 0 0 1 1 P12 1 — 3 — 3 0 1 1 P13 1 — 1 — 1 0 0 1 P14 1 — 0 — 0 0 1 0 P15 1 — 1 — 1 0 1 1 P18 1 — 2 — 1 0 1 1 P19 1 — 3 — 2 1 1 1 P20 0 — 0 — 0 0 0 0 P21 0 — 2 — 2 0 0 0 P22 1 — 1 — 1 1 1 0 P23 0 — 1 — 1 1 1 1 P24 1 — 0 — 1 0 1 1 P25 0 — 2 — 1 1 1 1 P26 0 — 1 — 1 0 1 1 P27 0 — 2 — 2 0 1 1 P28 1 — 1 — 0 0 1 0 P29 0 — 0 — 0 0 0 0 P30 1 — 1 — 1 1 1 1 P31 0 — 0 — 0 0 0 0 P32 0 — 1 — 1 0 0 1 P33 0 — 0 — 0 0 1 0 P34 0 — 0 — 0 0 0 0 P35 1 — 2 — 1 0 1 1 P37 0 — 1 — 1 1 1 1 P38 1 — 1 — 0 0 1 1 P39 0 — 0 — 0 1 1 1 P40 1 — 1 — 1 0 1 1 P41 1 — 4 — 4 1 1 1 P42 1 — 4 — 4 1 1 1 P43 1 — 4 — 3 1 2 1 P44 1 — 4 — 4 1 1 1 P45 0 — 1 — 1 0 0 1 P46 0 — 1 — 1 1 1 1 P47 0 — 1 — 1 0 0 0 P48 0 — 0 — 0 0 0 0 P49 0 — 1 — 1 1 0 0 P50 2 — 2 — 0 0 0 0 P51 0 — 0 — 0 0 0 0 P52 1 — 2 — 2 0 1 1 P53 0 — 0 — 1 1 1 0 P54 2 — 0 — 0 1 1 1 P55 0 — 0 — 0 0 0 0 P56 1 — 0 — 0 0 0 0 P57 0 — 1 — 1 0 0 0 P59 1 — 4 — 4 3 1 2 P60 1 — 1 — 1 1 1 1 P61 0 — 4 — 3 0 2 0 P62 0 — 4 — 3 0 0 1 P63 0 — 4 — 3 0 0 0 P64 0 — 4 — 3 0 1 1 P65 1 — 4 — 3 0 1 0 P66 0 — 4 — 4 0 1 1 P67 1 — 4 — 3 1 1 1 P68 0 — 3 — 3 0 0 1 P69 0 — 4 — 3 1 1 2 P70 0 — 4 — 3 0 1 0 P71 0 — 3 — 3 1 0 1 P72 0 — 4 — 3 1 0 1 P73 0 — 4 — 3 1 0 1 P74 1 — 4 — 4 0 1 1 P75 0 — 4 — 3 0 0 0 P76 1 — 4 — 3 1 2 1 P77 0 — 4 — 3 0 1 0 P78 1 — 3 — 3 0 3 0 P79 0 — 4 — 4 1 1 1 P80 0 — 4 — 3 1 1 1 P81 1 — 4 — 3 0 1 1 P82 0 — 0 — 1 1 1 1 P83 0 — 0 — 0 0 0 0 P84 0 — 4 — 2 1 1 0 P85 1 — 4 — 3 0 1 1 P86 0 — 4 — 4 0 0 0 P87 1 — 1 — 1 0 1 0 P88 0 — 4 — 3 0 1 0 P89 0 — 4 — 3 0 0 0 P90 0 — 4 — 3 1 0 1 P91 0 — 4 — 3 1 1 1 P92 1 — 3 — 3 2 2 1