TRIAZINE BENZOATE COMPOUND AND APPLICATION THEREOF

Abstract

The present invention discloses a triazine benzoate compound having the structure shown in formula (I) or a stereoisomer:

##STR00001##

The definition of each substituent in the formula I is described in the description. The compound of the formula I of the present invention has excellent herbicidal activity and can be used for controlling weeds.

Claims

1. A triazine benzoate compound, characterized in that the compound is shown in formula I: ##STR00383## wherein: W is selected from O or S; X.sub.1 is selected from H or F; X.sub.2 is selected from halogen, CN, CONH.sub.2 or CSNH.sub.2; R.sub.1 is selected from methyl or ethyl; R.sub.2 is selected from methyl or ethyl; R.sub.3 is selected from H or methyl; R.sub.4 is selected from H or C.sub.1-C.sub.3 alkyl; R.sub.5 is selected from CH.sub.3CH.sub.2—, CH.sub.3CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CH—, CH.sub.3CH.sub.2CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CHCH.sub.2—, CH.sub.3CH.sub.2CH(CH.sub.3)—, (CH.sub.3).sub.3C—, CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CHCH.sub.2CH.sub.2—, (CH.sub.3).sub.3CCH.sub.2—, CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2—, CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)—, CH.sub.3CH.sub.2C(CH.sub.3).sub.2—, CH.sub.3CH═CHCH.sub.2—, CH.sub.3C≡CCH.sub.2—, C.sub.1-C.sub.10 haloalkyl, C.sub.1-C.sub.6 alkylthio C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkylsulfinyl C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkylsulfonyl C.sub.1-C.sub.6 alkyl, (C.sub.1-C.sub.6 alkyl).sub.2 amino C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.3-C.sub.6 cycloalkyl C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10 halocycloalkyl, C.sub.3-C.sub.6 halocycloalkyl C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.10 haloalkenyl, C.sub.1-C.sub.6 alkoxy C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkylthio C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkylsulfinyl C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkylsulfonyl C.sub.2-C.sub.6 alkenyl, (C.sub.1-C.sub.6 alkyl).sub.2 amino C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.10 cycloalkenyl, C.sub.3-C.sub.6 cycloalkyl C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.6 halocycloalkyl C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.10 haloalkynyl, C.sub.1-C.sub.6 alkoxy C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 alkylthio C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 alkylsulfinyl C.sub.2-C.sub.6 alkynyl, C.sub.1-C.sub.6 alkylsulfonyl C.sub.2-C.sub.6 alkynyl, (C.sub.1-C.sub.6 alkyl).sub.2 amino C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.10 cycloalkynyl, C.sub.3-C.sub.6 cycloalkyl C.sub.2-C.sub.6 alkynyl, C.sub.3-C.sub.6 halocycloalkyl C.sub.2-C.sub.6 alkynyl, phenyl, phenyl C.sub.1-C.sub.6 alkyl, 5-7-membered alicyclic heterocycle containing 1-4 heteroatoms, 5-7-membered aromatic heterocycle containing 1-4 heteroatoms, 5-7-membered alicyclic heterocyclic C.sub.1-C.sub.6 alkyl containing 1-4 heteroatoms or 5-7 membered aromatic heterocyclic C.sub.1-C.sub.6 alkyl containing 1-4 heteroatoms; hydrogens on the above phenyl, alicyclic heterocycle and aromatic heterocycle can be substituted by one or more of the following substituents; and the substituents are selected from nitro, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 haloalkoxy, C.sub.3-C.sub.6 cycloalkyl, C.sub.3-C.sub.6 cycloalkoxy, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, phenyl or phenyl which is substituted by one or more halogens; or, an optical isomer of the compound shown in formula I when R.sub.3 is selected from H and R.sub.4 is not selected from H.

2. The compound according to claim 1, characterized in that in the formula I: W is selected from O or S; X.sub.1 is selected from H or F; X.sub.2 is selected from Cl, Br or CN; R.sub.1 is selected from methyl; R.sub.2 is selected from methyl; R.sub.3 is selected from H or methyl; R.sub.4 is selected from H, methyl, ethyl or isopropyl; R.sub.5 is selected from CH.sub.3CH.sub.2—, CH.sub.3CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CH—, CH.sub.3CH.sub.2CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CHCH.sub.2—, CH.sub.3CH.sub.2CH(CH.sub.3)—, (CH.sub.3).sub.3C—, CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CHCH.sub.2CH.sub.2—, (CH.sub.3).sub.3CCH.sub.2—, CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2—, CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)—, CH.sub.3CH.sub.2C(CH.sub.3).sub.2—, C.sub.1CH.sub.2CH.sub.2—, C.sub.1CH.sub.2CH.sub.2CH.sub.2—, CH.sub.3ClCHCH.sub.2—, CH.sub.2Cl(CH.sub.3)CH—, C.sub.1CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, CH.sub.3ClCHCH.sub.2CH.sub.2—, CH.sub.3CH.sub.2C.sub.1CHCH.sub.2—, CH.sub.3CH.sub.2CH.sub.2C.sub.1CH—, C.sub.1CH.sub.2CH.sub.2CH(CH.sub.3)—, C.sub.1CH.sub.2(CH.sub.3).sub.2C—, C.sub.1CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, CH.sub.3CH═CHCH.sub.2—, ClCH═CHCH.sub.2—, C.sub.12C═CHCH.sub.2—, C.sub.1CH═CClCH.sub.2—, CH.sub.3C≡CCH.sub.2—, ClC≡CCH.sub.2— or the following substituents: ##STR00384## or, an optical isomer of the compound shown in formula I when R.sub.3 is selected from H and R.sub.4 is not selected from H.

3. The compound according to claim 2, characterized in that in the formula I: W is selected from S; X.sub.1 is selected from F; X.sub.2 is selected from Cl; R.sub.1 is selected from methyl; R.sub.2 is selected from methyl; R.sub.3 is selected from H or methyl; R.sub.4 is selected from H or methyl; R.sub.5 is selected from CH.sub.3CH.sub.2—, CH.sub.3CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CH—, CH.sub.3CH.sub.2CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CHCH.sub.2—, CH.sub.3CH.sub.2CH(CH.sub.3)—, (CH.sub.3).sub.3C—, CH.sub.3CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, (CH.sub.3).sub.2CHCH.sub.2CH.sub.2—, (CH.sub.3).sub.3CCH.sub.2—, CH.sub.3CH.sub.2CH(CH.sub.3)CH.sub.2—, CH.sub.3CH.sub.2CH.sub.2CH(CH.sub.3)—, CH.sub.3CH.sub.2C(CH.sub.3).sub.2—, C.sub.1CH.sub.2CH.sub.2—, C.sub.1CH.sub.2CH.sub.2CH.sub.2—, CH.sub.3ClCHCH.sub.2—, CH.sub.2Cl(CH.sub.3)CH—, C.sub.1CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, CH.sub.3ClCHCH.sub.2CH.sub.2—, CH.sub.3CH.sub.2C.sub.1CHCH.sub.2—, CH.sub.3CH.sub.2CH.sub.2C.sub.1CH—, C.sub.1CH.sub.2CH.sub.2CH(CH.sub.3)—, C.sub.1CH.sub.2(CH.sub.3).sub.2C—, C.sub.1CH.sub.2CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, CH.sub.3CH═CHCH.sub.2—, ClCH═CHCH.sub.2—, C.sub.12C═CHCH.sub.2—, C.sub.1CH═CClCH.sub.2—, CH.sub.3C≡CCH.sub.2—, ClC≡CCH.sub.2— or the following substituents: ##STR00385## or, an optical isomer of the compound shown in formula I is S configuration or S configuration content is greater than 60% when R.sub.3 is selected from H and R.sub.4 is selected from methyl.

4. An application of the compound of the formula I of claim 1 in control for weeds.

5. A herbicidal composition, characterized in that the herbicidal composition comprises an active ingredient and an acceptable carrier; the active ingredient is the compound of the formula I of claim 1; and the weight percentage of the active ingredient in the composition is 1-99%.

6. A method for controlling weeds by the herbicidal composition of claim 5, characterized in that a herbicidally effective dose of the herbicidal composition of claim 5 is applied to a weed or a growth medium or site of the weed.

Description

DETAILED DESCRIPTION

[0072] The following synthesis embodiments and biometric test results can be used to further illustrate the present invention, but are not intended to limit the present invention.

SYNTHESIS EMBODIMENTS

Embodiment 1: Synthesis of Compound 1 2-chloro-4-fluoro-5-(3, 5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (1-ethoxycarbonyl) ethyl ester

[0073] ##STR00016##

Step a) Synthesis of Intermediate 2-chloro-4-fluoro-5-isopropyl nitrobenzoate

[0074] ##STR00017##

[0075] 2-chloro-4-fluoro-5-nitrobenzoic acid (13.20 g, 60 mmol), toluene (60 mL) and thionyl chloride (7.5 mL, 103 mmol) were added into a 250 mL reaction flask, and refluxed to react for 3 h. The reaction system is changed from a suspension to a clear solution. A solvent and excess thionyl chloride were evaporated under reduced pressure, and the residue was diluted with 20 mL of dichloromethane for later use.

[0076] Dichloromethane (60 mL), isopropanol (4.00 g, 67 mmol) and triethylamine (9.0 mL, 65 mmol) were added to another 250 mL reaction flask in sequence, and the above prepared acyl chloride dichloromethane solution was added to the flask at room temperature; and after dropwise adding, the mixture was continuously stirred for 2 h at room temperature. The reaction solution was poured into 100 mL of water and extracted with 50 mL of dichloromethane; and a combined organic layer was washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 14.40 g of yellow liquid with a crude yield of 92%. The obtained 2-chloro-4-fluoro-5-isopropyl nitrobenzoate is directly used for synthesis in the next step without further purification.

Step b) Synthesis of Intermediate 5-amino-2-chloro-4-isopropyl fluorobenzoate

[0077] ##STR00018##

[0078] 2-chloro-4-fluoro-5-isopropyl nitrobenzoate (14.40 g, 55 mmol) formed a solution with a mixed solvent formed by 30 mL of ethanol and 60 mL of tetrahydrofuran in the 250 mL reaction flask; reduced iron powder (11.00 g, 197 mmol) was added; concentrated hydrochloric acid (40 mL, about 480 mmol) was dropwise added to the mixture in an ice water bath; and after dropwise adding, the mixture was restored to room temperature to react for 1 h. the solvent was evaporated under reduced pressure; 100 mL of water was added to the residue; a combined organic layer was extracted (50 mL×3) with ethyl acetate, washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 13.00 g of brown liquid; and the brown liquid was cooled to obtain dark brown solid with a crude yield of 102%. The obtained 5-amino-2-chloro-4-isopropyl fluorobenzoate is directly used for synthesis in the next step without further purification. For purification, recrystallization can be conducted with ethanol to obtain yellow solid.

Step c) Synthesis of Intermediate 2-chloro-4-fluoro-5-(3, 5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)isopropyl benzoate

[0079] ##STR00019##

[0080] 50 mL of ethyl acetate was added into a 250 mL reaction flask; then, 5-amino-2-chloro-4-isopropyl fluorobenzoate (13.00 g, 56 mmol), triethylamine (9.0 mL, 65 mmol) and carbonyldiimidazole (DCI, 22.50 g, 140 mmol) were added successively to form a solution; and the solution was heated to 50° C. to react for 30 min. 1,3-dimethylurea (5.90 g, 67 mmol) was added into the solution, and the temperature was raised to reflux to react for 2 h. After the reaction was completed, 100 mL of ethyl acetate was added thereto, washed with saturated salt water (50 mL×2), dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain brown viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:9, then 1:4) was conducted to obtain 15.35 g of yellow liquid with a yield of 73%.

Step d) Synthesis of Intermediate 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid

[0081] ##STR00020##

[0082] 2-chloro-4-fluoro-5-(3, 5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)isopropyl benzoate (4.46 g, 12 mmol) and concentrated sulfuric acid (12.0 mL, 220 mmol) were added into a 100 mL reaction flask to form a solution; and the solution was heated to 80° C. to react for 4 h. After the reaction was completed, the reaction solution was poured into 60 mL of ice-water mixture, and the precipitated gray solid was obtained by filtration, rinsed twice with 30 mL of water, and air-dried to obtain 3.90 g of intermediate 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid with a yield of 98%.

Step e) Synthesis of Compound 1 2-chloro-4-fluoro-5-(3, 5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (1-ethoxycarbonyl) ethyl ester

[0083] ##STR00021##

[0084] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (0.50 g, 1.5 mmol), ethyl lactate (0.20 g, 1.7 mmol) and 4-(N,N-dimethylamino)pyridine (DMAP, 0.05 g, 0.4 mmol) were mixed and dissolved in 50 mL of dichloromethane in a 100 mL reaction flask to form grey-white suspension. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 0.60 g, 3.1 mmol) was added in batches into the reaction flask at room temperature, and the reaction system was changed from the suspension to a clear solution. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (15 mL×2); the combined organic layer was washed with 15 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain brown viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.27 g of compound 1, 2-chloro-4-fluoro-5-(3, 5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (1-ethoxycarbonyl) ethyl ester, i.e., yellow liquid with a yield of 41%.

Embodiment 2: Synthesis of Compound 33 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (1-(2-butynyloxycarbonyl))ethyl ester

[0085] ##STR00022##

Step a) Synthesis of Intermediate 2-bromopropanoate (2-butyn-1-ol)ester

[0086] ##STR00023##

[0087] In a 250 mL reaction flask, 2-bromopropionic acid 3.82 g, 25.0 mmol), 2-butyn-1-ol (1.80 g, 25.7 mmol), and 4-(N,N-dimethylamino)pyridine (DMAP, 0.60 g, 5.0 mmol) were mixed in 50 mL of dichloromethane to form a solution. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 9.60 g, 50.0 mmol) was added in batches into the reaction flask at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (25 mL×2); the combined organic layer was washed with 25 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 3.85 g of yellowish liquid with a yield of 75%. The liquid is directly used for reaction in the next step without further purification.

Step b) Synthesis of Compound 33 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (1-(2-butynyloxycarbonyl))ethyl ester

[0088] ##STR00024##

[0089] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (0.50 g, 1.5 mmol) and potassium carbonate (0.22 g, 1.6 mmol) were mixed and dissolved in 7.5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form grey-white suspension; and 2-bromopropanoate (2-butyn-1-ol)ester (0.33 g, 1.6 mmol) was added into the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 30 mL of water, and extracted with ethyl acetate (15 mL×3); the combined organic layer was washed with 15 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.45 g of compound 33, 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (1-(2-butynyloxycarbonyl))ethyl ester, i.e., yellow liquid with a yield of 66%.

Embodiment 3: Synthesis of Compound 42 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (2-methyl-1-ethoxycarbonyl)propyl ester

[0090] ##STR00025##

[0091] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (0.66 g, 2.0 mmol) and potassium carbonate (0.29 g, 2.1 mmol) were mixed and dissolved in 10 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form grey-white suspension; and 2-bromo-3-methylbutyric acid ethyl ester (0.42 g, 2.0 mmol, available in the market) was added into the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with ethyl acetate (20 mL×3); the combined organic layer was washed with 25 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.37 g of compound 42, 2-chloro-4-fluoro-5-(3,5-dimethyl-2,4,6-trioxo-1,3,5-triazine-1-yl)benzoic acid (2-methyl-1-ethoxycarbonyl)propyl ester, i.e., orange liquid with a yield of 40%.

Embodiment 4: Synthesis of Compound 154 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(3,3-dichloroallyloxycarbonyl))ethyl ester

[0092] ##STR00026##

Step a) Synthesis of Intermediate benzyl 2-chloro-5-nitrobenzoate

[0093] ##STR00027##

[0094] 2-chloro-5-nitrobenzoic acid (20.16 g, 100 mmol), toluene (100 mL) and thionyl chloride (12.5 mL, 170 mmol) were added into a 250 mL reaction flask, and refluxed to react for 3 h. The reaction system is changed from a suspension to a clear solution. A solvent and excess dichlorosulfoxide were evaporated under reduced pressure, and the residue was diluted with 50 mL of dichloromethane for later use.

[0095] Dichloromethane (100 mL), benzyl alcohol (12.50 g, 116 mmol) and triethylamine (15.0 mL, 108 mmol) were added into another 250 mL reaction flask successively, and the above prepared acyl chloride dichloromethane solution was added to the flask at room temperature; and after dropwise adding, the mixture was continuously stirred for 2 h at room temperature. The reaction solution was poured into 100 mL of water and extracted with 50 mL of dichloromethane; and a combined organic layer was washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 30.00 g of yellow liquid with a crude yield of 103%. The obtained benzyl 2-chloro-5-nitrobenzoate is directly used for synthesis in the next step without further purification.

Step b) Synthesis of Intermediate benzyl 5-amino-2-chlorobenzoate

[0096] ##STR00028##

[0097] benzyl 2-chloro-5-nitrobenzoate (30.00 g, 100 mmol) prepared in the above step formed a solution with a mixed solvent formed by 50 mL of ethanol and 50 mL of tetrahydrofuran in the 250 mL reaction flask; reduced iron powder (19.50 g, 350 mmol) was added; concentrated hydrochloric acid (66 mL, about 800 mmol) was dropwise added to the mixture in an ice water bath; and after dropwise adding, the mixture was restored to room temperature to react for 1 h. The solvent was evaporated under reduced pressure; 100 mL of water was added to the residue; a combined organic layer was extracted (50 mL×3) with ethyl acetate, washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 25.80 g of yellow liquid; and the yellow liquid was cooled to obtain dark yellow solid with a crude yield of 99%. The obtained benzyl 5-amino-2-chlorobenzoate is directly used for synthesis in the next step without further purification. For purification, recrystallization can be conducted with ethanol to obtain yellowish solid.

Step c) Synthesis of Intermediate benzyl 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoate

[0098] ##STR00029##

[0099] 100 mL of ethyl acetate was added into a 250 mL reaction flask; then, benzyl 5-amino-2-chlorobenzoate (25.80 g, 99 mmol), triethylamine (15.0 mL, 108 mmol) and carbonyldiimidazole (DCI, 40.00 g, 247 mmol) were added successively to form a solution; and the solution was heated to 50° C. to react for 30 min. 1,3-dimethylthiourea (11.00 g, 106 mmol) was added into the solution, and the temperature was raised to reflux to react for 2 h. After the reaction was completed, 100 mL of ethyl acetate was added thereto, washed with saturated salt water (50 mL×2), dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain brown viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:9, then 1:4) was conducted to obtain 27.50 g of yellow liquid with a yield of 66%. The obtained benzyl 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoate is directly used for synthesis in the next step without further purification. For purification, recrystallization can be conducted with ethyl acetate/ethanol mixed solvent to obtain white solid.

Step d) Synthesis of Intermediate 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid

[0100] ##STR00030##

[0101] Benzyl 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoate (18.68 g, 44.7 mmol) was dissolved in 50 mL of acetonitrile in a 250 mL reaction flask, and trimethylsilyl iodide (25.00 g, 125.0 mmol) was added at room temperature to the reaction flask; and the reaction was kept at room temperature overnight. After the reaction was completed, the reaction solution was poured into 60 mL of saturated aqueous sodium bicarbonate solution, and washed with methyl tert-butyl ether (50 mL×3); an aqueous layer was adjusted to pH=2-3 with concentrated hydrochloric acid, and then solid was precipitated, filtered and aired to obtain 13.60 g of intermediate 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid, i.e., yellowish solid, with a yield of 93%.

Step e) Synthesis of Compound 154 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(3,3-dichloroallyloxycarbonyl))ethyl ester

[0102] ##STR00031##

[0103] 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.50 g, 1.5 mmol), (3,3-dichloroallyl) lactate (0.35 g, 1.7 mmol) and 4-(N,N-dimethylamino)pyridine (DMAP, 0.05 g, 0.4 mmol) were mixed and dissolved in 15 mL of dichloromethane in a 100 mL reaction flask to form suspension. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 0.60 g, 3.1 mmol) was added in batches into the reaction flask at room temperature, and the reaction system was changed from the suspension to a clear solution. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (15 mL×2); the combined organic layer was washed with 15 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:6) was conducted to obtain 0.49 g of compound 154, 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(3,3-dichloroallyloxycarbonyl))ethyl ester, i.e., yellowish liquid with a yield of 63%.

Embodiment 5: Synthesis of Compound 166 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(solketal carbonyl))ethyl ester

[0104] ##STR00032##

Step a) Synthesis of Intermediate 2-bromopropionic acid (solketal) ester

[0105] ##STR00033##

[0106] In a 250 mL reaction flask, 2-bromopropionic acid (7.65 g, 50.0 mmol), solketal (7.00 g, 53.0 mmol), and 4-(N,N-dimethylamino)pyridine (DMAP, 1.22 g, 10.0 mmol) were mixed in 50 mL of dichloromethane to form a solution. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 14.40 g, 75.0 mmol) was added in batches into the reaction flask at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (50 mL×2); the combined organic layer was washed with 25 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 10.10 g of yellowish liquid with a yield of 76%. The liquid is directly used for reaction in the next step without further purification.

Step b) Synthesis of Compound 166 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(solketal carbonyl))ethyl ester

[0107] ##STR00034##

[0108] 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.33 g, 1.0 mmol) and potassium carbonate (0.18 g, 1.3 mmol) were mixed and dissolved in 5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form suspension; and 2-bromopropionic acid (solketal) ester (0.30 g, 1.1 mmol) was added into the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 20 mL of water, and extracted with ethyl acetate (10 mL×3); the combined organic layer was washed with 10 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.40 g of compound 166, 2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(solketal carbonyl))ethyl ester, i.e., colorless foam substance with a yield of 77%.

Embodiment 6: Synthesis of Compound 222 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (3-chloropropoxycarbonyl) methyl ester

[0109] ##STR00035##

Step a) Synthesis of Intermediate benzyl 2-chloro-4-fluoro-5-nitrobenzoate

[0110] ##STR00036##

2-chloro-5-nitrobenzoic acid (8.80 g, 40 mmol), toluene (40 mL) and thionyl chloride (5.0 mL, 68 mmol) were added into a 250 mL reaction flask, and refluxed to react for 3 h. The reaction system is changed from a suspension to a clear solution. A solvent and excess thionyl chloride were evaporated under reduced pressure, and the residue was diluted with 20 mL of dichloromethane for later use.

[0111] Dichloromethane (40 mL), benzyl alcohol (5.00 g, 46 mmol) and triethylamine (6.0 mL, 43 mmol) were added to another 250 mL reaction flask in sequence, and the above prepared acyl chloride dichloromethane solution was added to the flask at room temperature; and after dropwise adding, the mixture was continuously stirred for 2 h at room temperature. The reaction solution was poured into 100 mL of water and extracted with 50 mL of dichloromethane; and a combined organic layer was washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 13.00 g of yellow liquid with a crude yield of 105%. The obtained benzyl 2-chloro-4-fluoro-5-nitrobenzoate is directly used for synthesis in the next step without further purification.

Step b) Synthesis of Intermediate benzyl 5-amino-2-chloro-4-fluorobenzoate

[0112] ##STR00037##

[0113] In a 250 mL reaction flask, benzyl 2-chloro-4-fluoro-5-nitrobenzoate (7.75 g, 25 mmol) prepared in the above step and 25 mL of ethyl acetate formed a solution, and stannous chloride dihydrate (22.00 g, 98 mmol) was added, heated and refluxed to react for 2 h. The reaction solution was poured into 100 mL of ice-water mixture, and the pH of the system was adjusted to 9-10 with dilute NaOH solution. The separated precipitate was filtered and rinsed with ethyl acetate for several times. A combined organic layer was washed with 25 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 6.10 g of yellow liquid; and the yellow liquid was cooled to obtain brown solid with a crude yield of 87%. The obtained benzyl 5-amino-2-chloro-4-fluorobenzoate is directly used for synthesis in the next step without further purification. For purification, recrystallization can be conducted with ethanol to obtain yellow solid.

Step c) Synthesis of Intermediate 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzyl benzoate

[0114] ##STR00038##

[0115] 40 mL of ethyl acetate was added into a 250 mL reaction flask; then, benzyl 5-amino-2-chloro-4-fluorobenzoate (5.60 g, 20.0 mmol), triethylamine (3.5 mL, 25.0 mmol) and carbonyldiimidazole (DCI, 8.50 g, 52.4 mmol) were added successively to form a solution; and the solution was heated to 50° C. to react for 30 min. 1,3-dimethylthiourea (2.60 g, 25.0 mmol) was added into the solution, and the temperature was raised to reflux to react for 2 h. After the reaction was completed, 40 mL of ethyl acetate was added thereto, washed with saturated salt water (25 mL×2), dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain brown viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:9, then 1:4) was conducted to obtain 7.40 g of yellow liquid with a yield of 85%. The obtained 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzyl benzoate is directly used for synthesis in the next step without further purification. For purification, recrystallization can be conducted with ethyl acetate/ethanol mixed solvent to obtain white solid.

Step d) Synthesis of Intermediate 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid

[0116] ##STR00039##

[0117] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzyl benzoate (4.36 g, 10.0 mmol) was dissolved in 50 mL of methanol in a 100 mL reaction flask; 10% palladium-carbon catalyst (0.20 g, 0.2 mmol) was added to the reaction flask at room temperature; and a hydrogen flow was passed into the reaction flask at 50° C. to react for 4 h. After the reaction was completed, insolubles were removed by filtration; the reaction solution was poured into 60 mL of saturated aqueous sodium bicarbonate solution, and washed with methyl tert-butyl ether (50 mL×3); an aqueous layer was adjusted to pH=2-3 with concentrated hydrochloric acid, and then solid was precipitated, filtered and aired to obtain 2.88 g of intermediate 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid, i.e., yellowish solid, with a yield of 83%.

Step e) Synthesis of Compound 222 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (3-chloropropoxycarbonyl) methyl ester

[0118] ##STR00040##

[0119] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.42 g, 1.2 mmol) and potassium carbonate (0.20 g, 1.4 mmol) were mixed and dissolved in 5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form suspension; and 2-bromoacetic acid (3-chloropropanol) ester (0.28 g, 1.3 mmol) was added to the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 20 mL of water, and extracted with ethyl acetate (10 mL×3); the combined organic layer was washed with 10 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.55 g of compound 222, 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (3-chloropropoxycarbonyl) methyl ester, i.e., colorless foam substance with a yield of 94%.

Embodiment 7: Synthesis of Compound 241 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (cyclopropylmethoxycarbonyl) methyl ester

[0120] ##STR00041##

Step a) Synthesis of Intermediate 2-bromoacetic acid (cyclopropanemethanol) ester

[0121] ##STR00042##

[0122] In a 250 mL reaction flask, 2-bromoacetic acid (4.16 g, 30.0 mmol), cyclopropylmethanol (2.38 g, 33.0 mmol) and 4-(N,N-dimethylamino)pyridine (DMAP, 0.75 g, 6.0 mmol) were mixed in 30 mL of dichloromethane to form a solution. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 8.60 g, 45.0 mmol) was added in batches into the reaction flask at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (30 mL×2); the combined organic layer was washed with 25 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 3.60 g of colorless liquid with a yield of 62%. The liquid is directly used for reaction in the next step without further purification.

Step b) Synthesis of Compound 241 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (cyclopropylmethoxycarbonyl) methyl ester

[0123] ##STR00043##

[0124] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.42 g, 1.2 mmol) and potassium carbonate (0.20 g, 1.4 mmol) were mixed and dissolved in 5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form suspension; and 2-bromoacetic acid (cyclopropanemethanol) ester (0.25 g, 1.3 mmol) was added to the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 20 mL of water, and extracted with ethyl acetate (10 mL×3); the combined organic layer was washed with 10 mL of saturated saltwater, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.52 g of compound 241, 2-chloro-4-fluoro-5-(3, 5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (cyclopropylmethoxycarbonyl) methyl ester, i.e., colorless foam substance with a yield of 93%.

Embodiment 8: Compound 248 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzoic acid (1-ethoxycarbonyl)ethyl ester

[0125] ##STR00044##

Step a) Synthesis of Intermediate 2-chloro-4-fluoro-5-nitrobenzoic acid (1-ethoxycarbonyl)ethyl ester

[0126] ##STR00045##

[0127] 2-chloro-4-fluoro-5-nitrobenzoic acid (4.40 g, 20.0 mmol), toluene (20 mL) and thionyl chloride (3.0 mL, 41.1 mmol) were added into a 250 mL reaction flask, and refluxed to react for 3 h. The reaction system is changed from a suspension to a clear solution. A solvent and excess dichlorosulfoxide were evaporated under reduced pressure, and the residue was diluted with 10 mL of dichloromethane for later use.

[0128] Dichloromethane (20 mL), ethyl lactate (2.65 g, 22.4 mmol) and triethylamine (3.0 mL, 21.5 mmol) were added to another 250 mL reaction flask in sequence, and the above prepared acyl chloride dichloromethane solution was added to the flask at room temperature; and after dropwise adding, the mixture was continuously stirred for 2 h at room temperature. The reaction solution was poured into 50 mL of water and extracted with 50 mL of dichloromethane; and a combined organic layer was washed with 30 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 6.16 g of yellow liquid with a crude yield of 96%. The obtained 2-chloro-4-fluoro-5-nitrobenzoate benzoate (1-ethoxycarbonyl) ethyl ester is directly used for synthesis in the next step without further purification.

Step b) Synthesis of Intermediate 5-amino-2-chloro-4-fluorobenzoic acid (1-ethoxycarbonyl)ethyl ester

[0129] ##STR00046##

[0130] 2-chloro-4-fluoro-5-nitrobenzoic acid (1-ethoxy-1-oxo-2-propanol) ester (6.16 g, 19.3 mmol) formed a solution with a mixed solvent formed by 20 mL of ethanol and 20 mL of tetrahydrofuran in the 250 mL reaction flask; reduced iron powder (4.00 g, 71.6 mmol) was added; concentrated hydrochloric acid (15 mL, about 180 mmol) was dropwise added to the mixture in an ice water bath; and after dropwise adding, the mixture was restored to room temperature to react for 1 h. The solvent was evaporated under reduced pressure; 50 mL of water was added to the residue; a combined organic layer was extracted (30 mL×3) with ethyl acetate, washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 4.00 g of yellow liquid with a crude yield of 72%. The obtained 5-amino-2-chloro-4-fluorobenzoic acid (1-ethoxycarbonyl)ethyl ester is directly used for synthesis in the next step without further purification.

Step c) Synthesis of Compound 248 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzoic acid (1-ethoxycarbonyl)ethyl ester

[0131] ##STR00047##

[0132] 30 mL of ethyl acetate was added into a 250 mL reaction flask; then, 5-amino-2-chloro-4-fluorobenzoic acid (1-ethoxycarbonyl)ethyl ester (4.00 g, 13.8 mmol), triethylamine (2.5 mL, 18.0 mmol) and carbonyldiimidazole (DCI, 5.60 g, 34.5 mmol) were added successively to form a solution; and the solution was heated to 50° C. to react for 30 min. 1,3-dimethylthiourea (1.75 g, 16.8 mmol) was added into the solution, and the temperature was raised to reflux to react for 2 h. After the reaction was completed, 60 mL of ethyl acetate was added thereto, washed with saturated salt water (30 mL×2), dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain brown viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:9, then 1:4) was conducted to obtain 4.20 g of compound 248, 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzoic acid (1-ethoxycarbonyl)ethyl ester, i.e., yellow liquid with a yield of 68%. The purity is above 95.3%. (HPLC: 17.574 min (50.8%); 19.589 min (44.5%); chromatographic conditions: DAICEL Chemical Industries, Ltd. ChiralPak AD-H type chiral column, isopropanol:n-hexane=10:90, flow rate 1.0 mL/s, and detection wavelength 254 nm.)

Embodiment 9: Synthesis of Compound 266 (R)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-chloroethoxycarbonyl)ethyl ester

[0133] ##STR00048##

Step a) Synthesis of Intermediate (S)-2-bromopropionic acid (2-chloroethanol) ester

[0134] ##STR00049##

[0135] In a 250 mL reaction flask, (S)-2-bromopropionic acid (7.65 g, 50.0 mmol), 2-chloroethanol (4.10 g, 50.9 mmol), and 4-(N,N-dimethylamino)pyridine (DMAP, 1.22 g, 10.0 mmol) were mixed in 50 mL of dichloromethane to form a solution. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 19.20 g, 100.0 mmol) was added in batches into the reaction flask at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (50 mL×2); the combined organic layer was washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 8.50 g of yellow liquid with a yield of 79%. The liquid is directly used for reaction in the next step without further purification.

Step b) Synthesis of Compound 266 (R)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-chloroethoxycarbonyl)ethyl ester

[0136] ##STR00050##

[0137] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.24 g, 0.7 mmol) and potassium carbonate (0.10 g, 0.7 mmol) were mixed and dissolved in 5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form suspension; and (S)-2-bromopropionic acid (2-chloroethanol) ester (0.15 g, 0.7 mmol) was added to the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 20 mL of water, and extracted with ethyl acetate (10 mL×3); the combined organic layer was washed with 10 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.12 g of compound 266, (R)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-chloroethoxycarbonyl)ethyl ester, i.e., colorless foam substance with a yield of 36%. The purity is 96.7%. (HPLC: 18.167 min; chromatographic conditions: DAICEL Chemical Industries, Ltd. ChiralPak AD-H type chiral column, isopropanol:n-hexane=10:90, flow rate 1.0 mL/s, and detection wavelength 254 nm.)

Embodiment 10: Synthesis of Compound 267 (S)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-chloroethoxycarbonyl)ethyl ester

[0138] ##STR00051##

Step a) Synthesis of Intermediate (R)-2-bromopropionic acid (2-chloroethanol) ester

[0139] ##STR00052##

[0140] In a 250 mL reaction flask, (R)-2-bromopropionic acid (7.65 g, 50.0 mmol), 2-chloroethanol (4.10 g, 50.9 mmol), and 4-(N,N-dimethylamino)pyridine (DMAP, 1.22 g, 10.0 mmol) were mixed in 50 mL of dichloromethane to form a solution. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 19.20 g, 100.0 mmol) was added in batches into the reaction flask at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (50 mL×2); the combined organic layer was washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 8.50 g of yellow liquid with a yield of 79%. The liquid is directly used for reaction in the next step without further purification.

Step b) Synthesis of Compound 267 (S)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-chloroethoxycarbonyl)ethyl ester

[0141] ##STR00053##

[0142] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.24 g, 0.7 mmol) and potassium carbonate (0.10 g, 0.7 mmol) were mixed and dissolved in 5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form suspension; and (R)-2-bromopropionic acid (2-chloroethanol) ester (0.15 g, 0.7 mmol) was added to the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 20 mL of water, and extracted with ethyl acetate (10 mL×3); the combined organic layer was washed with 10 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.12 g of compound 267, (S)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-chloroethoxycarbonyl)ethyl ester, i.e., colorless foam substance with a yield of 36%. The purity is 95.8%. (HPLC: 20.650 min; chromatographic conditions: DAICEL Chemical Industries, Ltd. ChiralPak AD-H type chiral column, isopropanol:n-hexane=10:90, flow rate 1.0 mL/s, and detection wavelength 254 nm.)

Embodiment 11: Synthesis of Compound 281 (E)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(3-chloroallyloxycarbonyl))ethyl ester

[0143] ##STR00054##

[0144] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.42 g, 1.2 mmol), lactic acid (3-chloroallyl alcohol)ester (0.25 g, 1.5 mmol, available in the market) and 4-(N,N-dimethylamino)pyridine (DMAP, 0.03 g, 0.2 mmol) were mixed and dissolved in 15 mL of dichloromethane in a 100 mL reaction flask to form suspension. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 0.35 g, 1.8 mmol) was added in batches into the reaction flask at room temperature, and the reaction system was changed from the suspension to a clear solution. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (15 mL×2); the combined organic layer was washed with 15 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:6) was conducted to obtain 0.15 g of compound 281, (E)-2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(3-chloroallyloxycarbonyl))ethyl ester, i.e., colorless liquid with a yield of 25%.

Embodiment 12: Synthesis of Compound 298 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzoic acid (1-(isoxazolin-2-ylmethoxycarbonyl))ethyl ester

[0145] ##STR00055##

Step a) Synthesis of Intermediate 2-bromopropionyl chloride

[0146] ##STR00056##

[0147] In a 100 mL reaction flask, 2-bromopropionic acid (0.50 g, 3.27 mmol) was dissolved in 20 mL of dichloromethane; oxalyl chloride (1.66 g, 13.07 mmol) was added; and 2 drops of N,N-dimethylformamide were added dropwise at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The solvent and excess oxalyl chloride were spun off, and dissolved in 10 mL of dichloromethane for later use.

Step b) Synthesis of Intermediate 2-bromo-1-(isoxazolidine-2-yl)propan-1-one

[0148] ##STR00057##

[0149] In a 100 mL reaction flask, 4-hydroisoxazole hydrochloride (0.36 g, 3.27 mmol) was dissolved in 20 mL of dichloromethane; 2-bromopropionyl chloride obtained in the above step was added; and triethylamine (0.66 g, 6.54 mmol) was added. After the material was added, the material was stirred at room temperature for 2 h. The solvent was spun off, and was directly used for reaction in the next step without further purification.

Step c) Synthesis of Compound 298 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzoic acid (1-(isoxazolin-2-ylmethoxycarbonyl))ethyl ester

[0150] ##STR00058##

[0151] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1.00 g, 2.89 mmol) and potassium carbonate (0.72 g, 3.47 mmol) were mixed and dissolved in 5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form suspension; and 2-bromo-1-(isoxazolidine-2-yl)propan-1-one prepared in the above step was added to the suspension at room temperature. After the addition was completed, the temperature was raised to 80° C. and stirring was continued for 2 h. The reaction was completed after 2 h. The reaction solution was poured into 20 mL of water, and extracted with ethyl acetate (10 mL×3); the combined organic layer was washed with 10 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:PE.=1:4) was conducted to obtain 120 mg of target compound 298, 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl) benzoic acid (1-(isoxazolin-2-ylmethoxycarbonyl))ethyl ester, i.e., yellowish oily liquid with a yield of 9%.

Embodiment 13: Synthesis of Compound 300 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-fluoroethoxycarbonyl))propyl ester

[0152] ##STR00059##

Step a) Synthesis of Intermediate 2-bromobutyric acid (2-fluoroethanol) ester

[0153] ##STR00060##

[0154] In a 250 mL reaction flask, 2-bromobutyric acid (4.18 g, 25.0 mmol), 2-fluoroethanol (1.63 g, 25.5 mmol) and 4-(N,N-dimethylamino)pyridine (DMAP, 0.61 g, 5.0 mmol) were mixed in 25 mL of dichloromethane to form a solution. 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.Math.HCl, 9.60 g, 50.0 mmol) was added in batches into the reaction flask at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water, and extracted with dichloromethane (50 mL×2); the combined organic layer was washed with 50 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 3.60 g of yellow liquid with a yield of 68%. The liquid is directly used for reaction in the next step without further purification.

Step b) Synthesis of Compound 300 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-fluoroethoxycarbonyl))propyl ester

[0155] ##STR00061##

[0156] 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (0.52 g, 1.5 mmol) and potassium carbonate (0.22 g, 1.6 mmol) were mixed and dissolved in 5 mL of N,N-dimethylformamide (DMF) in a 100 mL reaction flask to form suspension; and 2-bromobutyric acid (2-fluoroethanol) ester (0.32 g, 1.5 mmol) was added to the suspension at room temperature. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 20 mL of water, and extracted with ethyl acetate (10 mL×3); the combined organic layer was washed with 10 mL of saturated salt water, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain yellow viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:4) was conducted to obtain 0.50 g of compound 300, 2-chloro-4-fluoro-5-(3, 5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-(2-fluoroethoxycarbonyl))propyl ester, i.e., colorless foam substance with a yield of 70%.

Embodiment 14: Compound 306 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester

[0157] ##STR00062##

Step a) Synthesis of Intermediate 2-chloro-4-fluoro-5-nitrobenzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester

[0158] ##STR00063##

[0159] 2-chloro-4-fluoro-5-nitrobenzoic acid (5.49 g, 25.0 mmol), ethyl α-hydroxyisobutyrate (4.00 g, 30.0 mmol), 4-(N,N-dimethylamino)pyridine (DMAP, 0.30 g, 2.5 mmol) and dichloromethane (50 mL) were added to a 250 mL reaction flask; 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC.Math.HCl, 9.60 g, 50.0 mmol) was added in batches to the reaction flask while stirring at room temperature; and the reaction system was changed from the suspension to a clear solution. After the material was added, the material was stirred at room temperature for 2 h. The reaction solution was poured into 50 mL of water and extracted with 50 mL of dichloromethane; and a combined organic layer was washed with 30 mL of saturated salt water, dried with anhydrous magnesium sulphate and concentrated under reduced pressure to obtain 2.70 g of yellow liquid with a crude yield of 33%. The obtained intermediate 2-chloro-4-fluoro-5-nitrobenzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester is directly used for synthesis in the next step without further purification.

Step b) Synthesis of Intermediate 5-amino-2-chloro-4-fluorobenzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester

[0160] ##STR00064##

[0161] In a 100 mL reaction flask, 2-chloro-4-fluoro-5-nitrobenzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester (2.70 g, 8.10 mmol) was mixed with 20 mL of methanol to form a solution; 10% palladium/carbon catalyst (0.25 g) was added; and a hydrogen flow was introduced for 2 h through the reaction at room temperature. After the TLC monitored that the reaction was completed, the catalyst is removed through filtration. The solvent was evaporated out from the filtrate under reduced pressure to obtain 1.80 g of yellow liquid with a crude yield of 73%. The obtained 5-amino-2-chloro-4-fluorobenzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester is directly used for synthesis in the next step without further purification.

Step c) Synthesis of Compound 306 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester

[0162] ##STR00065##

[0163] 15 mL of toluene was added to a 100 mL reaction flask; 5-amino-2-chloro-4-fluorobenzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester (1.80 g, 6.0 mmol) and triphosgene (0.90 g, 3.0 mmol) were added in sequence; the solution was heated to reflux and the reaction was kept under the reflux condition for 2 h. After returning to room temperature, a toluene solution of isocyanate was obtained for later use.

[0164] 15 mL of toluene, 1,3-dimethylthiourea (1.75 g, 16.8 mmol) and triethylamine (1.0 mL, 7.2 mmol) were successively added to another 100 mL reaction flask; the above prepared toluene solution of isocyanate was added dropwise to the reaction flask at room temperature; after dropwise adding, carbonyldiimidazole (DCI, 1.45 g, 9.0 mmol) was added, and heated to reflux; and the reaction was kept under the reflux condition for 2 h. After the reaction was completed, 30 mL of toluene was added thereto, washed with saturated salt water (15 mL×2), dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain brown viscous liquid. Column chromatography separation (SiO.sub.2, EtOAc:P.E.=1:9, then 1:4) was conducted to obtain 1.80 g of compound 306, 2-chloro-4-fluoro-5-(3,5-dimethyl-2,6-dioxo-4-thio-1,3,5-triazine-1-yl)benzoic acid (1-methyl-1-ethoxycarbonyl)ethyl ester, i.e., white solid (m.p. 98-100° C.) with a yield of 66%.

[0165] The initial substances are replaced according to the above recorded method to obtain other compounds shown by the formula I. The structures and physical properties of part of the compounds of the formula I can be found in Table 1.

##STR00066##

TABLE-US-00001 TABLE 1 Melting Compound W X.sub.1 X.sub.2 R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 Configuration Point/° C. 1. O F Cl Me Me H Me Et yellow oil 2. O F Cl Me Me H Me n-Pr 3. O F Cl Me Me H Me i-Pr 4. O F Cl Me Me H Me n-Bu 5. O F Cl Me Me H Me i-Bu 6. O F Cl Me Me H Me s-Bu 7. O F Cl Me Me H Me t-Bu 8. O F Cl Me Me H Me [00067] 9. O F Cl Me Me H Me [00068] 10. O F Cl Me Me H Me [00069] 11. O F Cl Me Me H Me [00070] 12. O F Cl Me Me H Me [00071] 13. O F Cl Me Me H Me [00072] 14. O F Cl Me Me H Me [00073] 15. O F Cl Me Me H Me [00074] yellow oil 16. O F Cl Me Me H Me [00075] yellow oil 17. O F Cl Me Me H Me [00076] 18. O F Cl Me Me H Me [00077] 19. O F Cl Me Me H Me [00078] yellow oil 20. O F Cl Me Me H Me [00079] 21. O F Cl Me Me H Me [00080] 22. O F Cl Me Me H Me [00081] 23. O F Cl Me Me H Me [00082] 24. O F Cl Me Me H Me [00083] 25. O F Cl Me Me H Me [00084] 26. O F Cl Me Me H Me [00085] 27. O F Cl Me Me H Me [00086] 28. O F Cl Me Me H Me [00087] 29. O F Cl Me Me H Me [00088] 30. O F Cl Me Me H Me [00089] 31. O F Cl Me Me H Me [00090] 32. O F Cl Me Me H Me [00091] 33. O F Cl Me Me H Me [00092] yellow oil 34. O F Cl Me Me H Me [00093] 35. O F Cl Me Me H Me [00094] yellow oil 36. O F Cl Me Me H Me [00095] 37. O F Cl Me Me H Me [00096] yellow oil 38. O F Cl Me Me H Me [00097] 39. O F Cl Me Me H Me [00098] 40. O F Cl Me Me H Me [00099] 41. O F Cl Me Me H Et Et yellow oil 42. O F Cl Me Me H i-Pr Et orange oil 43. O F Cl Me Me Me Me Et 44. O F Cl Me Me Me Me n-Pr 45. O F Cl Me Me Me Me i-Pr 46. O F Cl Me Me Me Me n-Bu 47. O F Cl Me Me Me Me i-Bu 48. O F Cl Me Me Me Me s-Bu 49. O F Cl Me Me Me Me t-Bu 50. O F Cl Me Me Me Me [00100] 51. O F Cl Me Me Me Me [00101] 52. O F Cl Me Me Me Me [00102] 53. O F Cl Me Me Me Me [00103] 54. O F Cl Me Me Me Me [00104] 55. O F Cl Me Me Me Me [00105] 56. O F Cl Me Me Me Me [00106] 57. O F Cl Me Me Me Me [00107] 58. O F Cl Me Me Me Me [00108] 59. O F Cl Me Me Me Me [00109] 60. O F Cl Me Me Me Me [00110] 61. O F Cl Me Me Me Me [00111] 62. O F Cl Me Me Me Me [00112] 63. O F Cl Me Me Me Me [00113] 64. O F Cl Me Me Me Me [00114] 65. O F Cl Me Me Me Me [00115] 66. O F Cl Me Me Me Me [00116] 67. O F Cl Me Me Me Me [00117] 68. O F Cl Me Me Me Me [00118] 69. O F Cl Me Me Me Me [00119] 70. O F Cl Me Me Me Me [00120] 71. O F Cl Me Me Me Me [00121] 72. O F Cl Me Me Me Me [00122] 73. O F Cl Me Me Me Me [00123] 74. O F Cl Me Me Me Me [00124] 75. O F Cl Me Me Me Me [00125] 76. O F Cl Me Me Me Me [00126] 77. O F Cl Me Me Me Me [00127] 78. O F Cl Me Me Me Me [00128] 79. O F Cl Me Me Me Me [00129] 80. O F Cl Me Me Me Me [00130] 81. O F Cl Me Me Me Me [00131] 82. O F Cl Me Me Me Me [00132] 83. S H Cl Me Me H H Et 84. S H Cl Me Me H H n-Pr 85. S H Cl Me Me H H i-Pr 86. S H Cl Me Me H H n-Bu 87. S H Cl Me Me H H i-Bu 88. S H Cl Me Me H H s-Bu 89. S H Cl Me Me H H t-Bu 90. S H Cl Me Me H H [00133] 91. S H Cl Me Me H H [00134] 92. S H Cl Me Me H H [00135] 93. S H Cl Me Me H H [00136] 94. S H Cl Me Me H H [00137] 95. S H Cl Me Me H H [00138] 96. S H Cl Me Me H H [00139] 97. S H Cl Me Me H H [00140] white wax 98. S H Cl Me Me H H [00141] 99. S H Cl Me Me H H [00142] 100. S H Cl Me Me H H [00143] 101. S H Cl Me Me H H [00144] 102. S H Cl Me Me H H [00145] 103. S H Cl Me Me H H [00146] 104. S H Cl Me Me H H [00147] 105. S H Cl Me Me H H [00148] 106. S H Cl Me Me H H [00149] 107. S H Cl Me Me H H [00150] 108. S H Cl Me Me H H [00151] 109. S H Cl Me Me H H [00152] 110. S H Cl Me Me H H [00153] 111. S H Cl Me Me H H [00154] 112. S H Cl Me Me H H [00155] 113. S H Cl Me Me H H [00156] 114. S H Cl Me Me H H [00157] 115. S H Cl Me Me H H [00158] 116. S H Cl Me Me H H [00159] 117. S H Cl Me Me H H [00160] colorless foam 118. S H Cl Me Me H H [00161] 119. S H Cl Me Me H H [00162] 120. S H Cl Me Me H H [00163] 121. S H Cl Me Me H H [00164] colorless foam 122. S H Cl Me Me H H [00165] 123. S H Cl Me Me H H [00166] yellow oil 124. S H Cl Me Me H Me Et 125. S H Cl Me Me H Me n-Pr 126. S H Cl Me Me H Me i-Pr 127. S H Cl Me Me H Me n-Bu 128. S H Cl Me Me H Me i-Bu 129. S H Cl Me Me H Me s-Bu 130. S H Cl Me Me H Me t-Bu 131. S H Cl Me Me H Me [00167] 132. S H Cl Me Me H Me [00168] 133. S H Cl Me Me H Me [00169] 134. S H Cl Me Me H Me [00170] 135. S H Cl Me Me H Me [00171] 136. S H Cl Me Me H Me [00172] 137. S H Cl Me Me H Me [00173] 138. S H Cl Me Me H Me [00174] rac. colorless foam 139. S H Cl Me Me H Me [00175] R colorless oil 140. S H Cl Me Me H Me [00176] S pale yellow foam 141. S H Cl Me Me H Me [00177] 142. S H Cl Me Me H Me [00178] 143. S H Cl Me Me H Me [00179] 144. S H Cl Me Me H Me [00180] 145. S H Cl Me Me H Me [00181] 146. S H Cl Me Me H Me [00182] 147. S H Cl Me Me H Me [00183] 148. S H Cl Me Me H Me [00184] 149. S H Cl Me Me H Me [00185] 150. S H Cl Me Me H Me [00186] 151. S H Cl Me Me H Me [00187] 152. S H Cl Me Me H Me [00188] yellow oil 153. S H Cl Me Me H Me [00189] 154. S H Cl Me Me H Me [00190] pale yellow oil 155. S H Cl Me Me H Me [00191] 156. S H Cl Me Me H Me [00192] 157. S H Cl Me Me H Me [00193] 158. S H Cl Me Me H Me [00194] 159. S H Cl Me Me H Me [00195] 160. S H Cl Me Me H Me [00196] yellow foam 161. S H Cl Me Me H Me [00197] 162. S H Cl Me Me H Me [00198] 163. S H Cl Me Me H Me [00199] 164. S H Cl Me Me H Me [00200] colorless foam 165. S H Cl Me Me H Me [00201] 166. S H Cl Me Me H Me [00202] colorless foam 167. S H Cl Me Me Me Me Et 168. S H Cl Me Me Me Me n-Pr 169. S H Cl Me Me Me Me i-Pr 170. S H Cl Me Me Me Me n-Bu 171. S H Cl Me Me Me Me i-Bu 172. S H Cl Me Me Me Me s-Bu 173. S H Cl Me Me Me Me t-Bu 174. S H Cl Me Me Me Me [00203] 175. S H Cl Me Me Me Me [00204] 176. S H Cl Me Me Me Me [00205] 177. S H Cl Me Me Me Me [00206] 178. S H Cl Me Me Me Me [00207] 179. S H Cl Me Me Me Me [00208] 180. S H Cl Me Me Me Me [00209] 181. S H Cl Me Me Me Me [00210] 182. S H Cl Me Me Me Me [00211] 183. S H Cl Me Me Me Me [00212] 184. S H Cl Me Me Me Me [00213] 185. S H Cl Me Me Me Me [00214] 186. S H Cl Me Me Me Me [00215] 187. S H Cl Me Me Me Me [00216] 188. S H Cl Me Me Me Me [00217] 189. S H Cl Me Me Me Me [00218] 190. S H Cl Me Me Me Me [00219] 191. S H Cl Me Me Me Me [00220] 192. S H Cl Me Me Me Me [00221] 193. S H Cl Me Me Me Me [00222] 194. S H Cl Me Me Me Me [00223] 195. S H Cl Me Me Me Me [00224] 196. S H Cl Me Me Me Me [00225] 197. S H Cl Me Me Me Me [00226] 198. S H Cl Me Me Me Me [00227] 199. S H Cl Me Me Me Me [00228] 200. S H Cl Me Me Me Me [00229] 201. S H Cl Me Me Me Me [00230] 202. S H Cl Me Me Me Me [00231] 203. S H Cl Me Me Me Me [00232] 204. S H Cl Me Me Me Me [00233] 205. S H Cl Me Me Me Me [00234] 206. S H Cl Me Me Me Me [00235] 207. S F Cl Me Me H H Et 208. S F Cl Me Me H H n-Pr 209. S F Cl Me Me H H i-Pr 210. S F Cl Me Me H H n-Bu 211. S F Cl Me Me H H i-Bu 212. S F Cl Me Me H H s-Bu 213. S F Cl Me Me H H t-Bu 214. S F Cl Me Me H H [00236] 215. S F Cl Me Me H H [00237] 216. S F Cl Me Me H H [00238] 217. S F Cl Me Me H H [00239] 218. S F Cl Me Me H H [00240] 219. S F Cl Me Me H H [00241] 220. S F Cl Me Me H H [00242] 221. S F Cl Me Me H H [00243] yellow oil 222. S F Cl Me Me H H [00244] colorless foam 223. S F Cl Me Me H H [00245] 224. S F Cl Me Me H H [00246] 225. S F Cl Me Me H H [00247] yellow oil 226. S F Cl Me Me H H [00248] 227. S F Cl Me Me H H [00249] 228. S F Cl Me Me H H [00250] 229. S F Cl Me Me H H [00251] 230. S F Cl Me Me H H [00252] 231. S F Cl Me Me H H [00253] 232. S F Cl Me Me H H [00254] 233. S F Cl Me Me H H [00255] 234. S F Cl Me Me H H [00256] 235. S F Cl Me Me H H [00257] 236. S F Cl Me Me H H [00258] 237. S F Cl Me Me H H [00259] 238. S F Cl Me Me H H [00260] 239. S F Cl Me Me H H [00261] 240. S F Cl Me Me H H [00262] 241. S F Cl Me Me H H [00263] colorless foam 242. S F Cl Me Me H H [00264] 243. S F Cl Me Me H H [00265] 244. S F Cl Me Me H H [00266] 245. S F Cl Me Me H H [00267] colorless foam 246. S F Cl Me Me H H [00268] colorless oil 247. S F Cl Me Me H H [00269] colorless foam 248. S F Cl Me Me H Me Et rac. yellow oil 249. S F Cl Me Me H Me Et R colorless foam 250. S F Cl Me Me H Me Et S yellow foam 251. S F Cl Me Me H Me n-Pr 252. S F Cl Me Me H Me i-Pr 253. S F Cl Me Me H Me n-Bu 254. S F Cl Me Me H Me i-Bu 255. S F Cl Me Me H Me s-Bu 256. S F Cl Me Me H Me t-Bu 257. S F Cl Me Me H Me [00270] 258. S F Cl Me Me H Me [00271] 259. S F Cl Me Me H Me [00272] 260. S F Cl Me Me H Me [00273] 261. S F Cl Me Me H Me [00274] 262. S F Cl Me Me H Me [00275] 263. S F Cl Me Me H Me [00276] 264. S F Cl Me Me H Me [00277] colorless oil 265. S F Cl Me Me H Me [00278] rac. colorless foam 266. S F Cl Me Me H Me [00279] R colorless foam 267. S F Cl Me Me H Me [00280] S colorless foam 268. S F Cl Me Me H Me [00281] rac. colorless foam 269. S F Cl Me Me H Me [00282] R colorless foam 270. S F Cl Me Me H Me [00283] S colorless foam 271. S F Cl Me Me H Me [00284] 272. S F Cl Me Me H Me [00285] 273. S F Cl Me Me H Me [00286] yellow oil 274. S F Cl Me Me H Me [00287] 275. S F Cl Me Me H Me [00288] 276. S F Cl Me Me H Me [00289] 277. S F Cl Me Me H Me [00290] 278. S F Cl Me Me H Me [00291] 279. S F Cl Me Me H Me [00292] 280. S F Cl Me Me H Me [00293] 281. S F Cl Me Me H Me [00294] colorless oil 282. S F Cl Me Me H Me [00295] 283. S F Cl Me Me H Me [00296] pale yellow oil 284. S F Cl Me Me H Me [00297] 285. S F Cl Me Me H Me [00298] 286. S F Cl Me Me H Me [00299] 287. S F Cl Me Me H Me [00300] yellow oil 288. S F Cl Me Me H Me [00301] 289. S F Cl Me Me H Me Bn yellow oil 290. S F Cl Me Me H Me [00302] colorless foam 291. S F Cl Me Me H Me [00303] yellow oil 292. S F Cl Me Me H Me [00304] 293. S F Cl Me Me H Me [00305] yellow oil 294. S F Cl Me Me H Me [00306] 295. S F Cl Me Me H Me [00307] colorless foam 296. S F Cl Me Me H Me [00308] colorless oil 297. S F Cl Me Me H Me [00309] colorless foam 298. S F Cl Me Me H Me [00310] pale yellow oil 299. S F Cl Me Me H Et Et yellow oil 300. S F Cl Me Me H Et [00311] colorless foam 301. S F Cl Me Me H Et [00312] yellow foam 302. S F Cl Me Me H Et [00313] yellow foam 303. S F Cl Me Me H Et [00314] yellow oil 304. S F Cl Me Me H Et [00315] yellow oil 305. S F Cl Me Me H i-Pr Et yellow oil 306. S F Cl Me Me Me Me Et white solid 98~100 307. S F Cl Me Me Me Me n-Pr 308. S F Cl Me Me Me Me i-Pr 309. S F Cl Me Me Me Me n-Bu 310. S F Cl Me Me Me Me i-Bu 311. S F Cl Me Me Me Me s-Bu 312. S F Cl Me Me Me Me t-Bu 313. S F Cl Me Me Me Me [00316] 314. S F Cl Me Me Me Me [00317] 315. S F Cl Me Me Me Me [00318] 316. S F Cl Me Me Me Me [00319] 317. S F Cl Me Me Me Me [00320] 318. S F Cl Me Me Me Me [00321] 319. S F Cl Me Me Me Me [00322] 320. S F Cl Me Me Me Me [00323] 321. S F Cl Me Me Me Me [00324] 322. S F Cl Me Me Me Me [00325] 323. S F Cl Me Me Me Me [00326] 324. S F Cl Me Me Me Me [00327] 325. S F Cl Me Me Me Me [00328] 326. S F Cl Me Me Me Me [00329] 327. S F Cl Me Me Me Me [00330] 328. S F Cl Me Me Me Me [00331] 329. S F Cl Me Me Me Me [00332] 330. S F Cl Me Me Me Me [00333] 331. S F Cl Me Me Me Me [00334] 332. S F Cl Me Me Me Me [00335] 333. S F Cl Me Me Me Me [00336] 334. S F Cl Me Me Me Me [00337] 335. S F Cl Me Me Me Me [00338] 336. S F Cl Me Me Me Me [00339] 337. S F Cl Me Me Me Me [00340] 338. S F Cl Me Me Me Me [00341] 339. S F Cl Me Me Me Me [00342] 340. S F Cl Me Me Me Me [00343] 341. S F Cl Me Me Me Me [00344] 342. S F Cl Me Me Me Me [00345] 343. S F Cl Me Me Me Me [00346] 344. S F Cl Me Me Me Me [00347] 345. S F Cl Me Me Me Me [00348] 346. S F Cl Et Et H Me Et 347. S F Cl Et Et H Me n-Pr 348. S F Cl Et Et H Me i-Pr 349. S F Cl Et Et H Me n-Bu 350. S F Cl Et Et H Me i-Bu 351. S F Cl Et Et H Me s-Bu 352. S F Cl Et Et H Me t-Bu 353. S F Cl Et Et H Me [00349] 354. S F Cl Et Et H Me [00350] 355. S F Cl Et Et H Me [00351] 356. S F Cl Et Et H Me [00352] 357. S F Cl Et Et H Me [00353] 358. S F Cl Et Et H Me [00354] 359. S F Cl Et Et H Me [00355] 360. S F Cl Et Et H Me [00356] 361. S F Cl Et Et H Me [00357] 362. S F Cl Et Et H Me [00358] 363. S F Cl Et Et H Me [00359] 364. S F Cl Et Et H Me [00360] 365. S F Cl Et Et H Me [00361] 366. S F Cl Et Et H Me [00362] 367. S F Cl Et Et H Me [00363] 368. S F Cl Et Et H Me [00364] 369. S F Cl Et Et H Me [00365] 370. S F Cl Et Et H Me [00366] 371. S F Cl Et Et H Me [00367] 372. S F Cl Et Et H Me [00368] 373. S F Cl Et Et H Me [00369] 374. S F Cl Et Et H Me [00370] 375. S F Cl Et Et H Me [00371] 376. S F Cl Et Et H Me [00372] 377. S F Cl Et Et H Me [00373] 378. S F Cl Et Et H Me [00374] 379. S F Cl Et Et H Me [00375] 380. S F Cl Et Et H Me [00376] 381. S F Cl Et Et H Me [00377] 382. S F Cl Et Et H Me [00378] 383. S F Cl Et Et H Me [00379] 384. S F Cl Et Et H Me [00380] 385. S F Cl Et Et H Me [00381]

[0166] .sup.1H NMR (CDCl.sub.3, 600 MHz) δ (ppm) data of part of compounds is as follows:

[0167] Compound 1 8.00 (d, 1H, J=7.2 Hz), 7.39 (d, 1H, J=8.4 Hz), 5.32 (q, 1H, J=7.2 Hz), 4.23 (q, 2H, J=7.2 Hz), 3.42 (s, 6H), 1.60 (d, 3H, J=7.2 Hz), 1.29 (t, 3H, J=7.2 Hz).

[0168] Compound 15 8.02 (d, 1H, J=7.8 Hz), 7.40 (d, 1H, J=9.0 Hz), 5.37 (q, 1H, J=7.2 Hz), 4.40-4.46 (m, 2H), 3.70 (t, 2H, J=6.0 Hz), 3.42 (2s, 6H), 1.65 (d, 3H, J=6.6 Hz).

[0169] Compound 16 8.00 (d, 1H, J=7.2 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.33 (q, 1H, J=7.2 Hz), 4.35 (t, 2H, J=6.0 Hz), 3.60 (t, 2H, J=6.6 Hz), 3.43 (2s, 6H), 2.09-2.17 (m, 2H), 1.62 (d, 3H, J=6.6 Hz).

[0170] Compound 19 8.01 (d, 1H, J=7.2 Hz), 7.40 (d, 1H, J=9.0 Hz), 5.32 (q, 1H, J=6.6 Hz), 4.22 (t, 2H, J=6.0 Hz), 3.56 (t, 2H, J=6.0 Hz), 3.42 (2s, 6H), 1.83-1.85 (m, 4H), 1.62 (d, 3H, J=6.0 Hz).

[0171] Compound 33 8.01 (d, 1H, J=7.8 Hz), 7.40 (d, 1H, J=9.6 Hz), 5.36 (q, 1H, J=7.2 Hz), 4.74 (dq, 2H, J=15.0 Hz, J=2.4 Hz), 3.43 (2s, 6H), 1.86 (t, 3H, J=2.4 Hz), 1.63 (d, 3H, J=7.2 Hz).

[0172] Compound 35 8.02 (d, 1H, J=7.2 Hz), 7.40 (d, 1H, J=9.6 Hz), 5.34 (q, 1H, J=6.6 Hz), 4.01 (m, 2H), 3.43 (2s, 6H), 1.62 (d, 3H, J=6.6 Hz), 1.11-1.18 (m, 1H), 0.55-0.59 (m, 2H), 0.27-0.30 (m, 2H).

[0173] Compound 37 8.01 (d, 1H, J=7.2 Hz), 7.40 (d, 1H, J=9.0 Hz), 5.33 (q, 1H, J=6.6 Hz), 4.03-4.10 (m, 2H), 3.42 (2s, 6H), 2.18-2.26 (m, 1H), 1.71-1.77 (m, 2H), 1.61 (d, 3H, J=6.6 Hz), 1.50-1.61 (m, 4H), 1.20-1.25 (m, 2H).

[0174] Compound 41 7.99 (d, 1H, J=8.4 Hz), 7.40 (d, 1H, J=9.0 Hz), 5.19 (dd, 1H, J=4.8 Hz, J=7.2 Hz), 4.20-4.28 (m, 2H), 3.43 (2s, 6H), 1.96-2.07 (m, 2H), 1.29 (t, 3H, J=7.2 Hz), 1.06 (t, 3H, J=7.2 Hz).

[0175] Compound 42 7.97 (d, 1H, J=7.8 Hz), 7.40 (d, 1H, J=9.0 Hz), 5.09 (d, 1H, J=4.2 Hz), 4.20-4.28 (m, 2H), 3.43 (2s, 6H), 2.34-2.39 (m, 1H), 1.29 (t, 3H, J=7.2 Hz), 1.08 (d, 3H, J=6.6 Hz), 1.06 (d, 3H, J=6.6 Hz).

[0176] Compound 97 7.95 (d, 1H, J=3.0 Hz), 7.63 (d, 1H, J=8.4 Hz), 7.39 (dd, 1H, J=2.4 Hz, J=8.4 Hz), 4.91 (s, 2H), 4.45 (t, 2H, J=6.0 Hz), 3.78 (s, 6H), 3.71 (t, 2H, J=6.0 Hz).

[0177] Compound 117 7.94 (d, 1H, J=2.4 Hz), 7.62 (d, 1H, J=8.4 Hz), 7.38 (dd, 1H, J=3.0 Hz, J=8.4 Hz), 4.87 (s, 2H), 4.03 (d, 2H, J=7.2 Hz), 3.78 (s, 6H), 1.15 (m, 1H), 0.58 (m, 2H), 0.30 (m, 2H).

[0178] Compound 121 7.94 (d, 1H, J=3.0 Hz), 7.62 (d, 1H, J=7.8 Hz), 7.39 (dd, 1H, J=3.0 Hz, J=7.8 Hz), 4.91 (s, 2H), 4.53 (dd, 1H, J=2.4 Hz, J=12.6 Hz), 4.05 (dd, J=6.6 Hz, J=12.0 Hz), 3.78 (s, 6H), 3.23 (ddd, 1H, J=3.0 Hz, J=4.2 Hz, J=9.6 Hz), 2.86 (t, 1H, J=4.2 Hz), 2.66 (dd, 1H, J=2.4 Hz, J=4.8 Hz).

[0179] Compound 123 7.96 (d, 1H, J=3.0 Hz), 7.62 (d, 1H, J=7.8 Hz), 7.39 (dd, 1H, J=2.4 Hz, J=8.4 Hz), 4.89 (2d, 2H, J=15.6 Hz), 4.31-4.36 (m, 2H), 4.17-4.20 (m, 1H), 4.06-4.08 (m, 1H), 3.78 (s, 6H), 3.76-3.78 (m, 1H), 1.42 (s, 3H), 1.35 (s, 3H).

[0180] Compound 138 7.91 (d, 1H, J=2.4 Hz), 7.61 (d, 1H, J=7.8 Hz), 7.37 (dd, 1H, J=3.0 Hz, J=8.4 Hz), 5.38 (q, 1H, J=7.2 Hz), 4.38-4.47 (m, 2H), 3.78 (s, 6H), 3.71 (t, 2H, J=6.0 Hz), 1.65 (d, 3H, J=7.2 Hz).

[0181] Compound 139 7.91 (d, 1H, J=2.4 Hz), 7.61 (d, 1H, J=7.8 Hz), 7.37 (dd, 1H, J=3.0 Hz, J=8.4 Hz), 5.38 (q, 1H, J=7.2 Hz), 4.38-4.47 (m, 2H), 3.78 (s, 6H), 3.70 (t, 2H, J=6.0 Hz), 1.65 (d, 3H, J=7.2 Hz).

[0182] Compound 140 7.91 (d, 1H, J=2.4 Hz), 7.61 (d, 1H, J=7.8 Hz), 7.37 (dd, 1H, J=3.0 Hz, J=8.4 Hz), 5.38 (q, 1H, J=7.2 Hz), 4.38-4.47 (m, 2H), 3.78 (s, 6H), 3.70 (t, 2H, J=6.0 Hz), 1.65 (d, 3H, J=7.2 Hz).

[0183] Compound 152 7.88 (d, 1H, J=3.0 Hz), 7.62 (d, 1H, J=8.4 Hz), 7.37 (dd, 1H, J=3.0 Hz, J=8.4 Hz), 6.37 (ddt, 1H, J=6.6 Hz, J=14.4 Hz, J=1.2 Hz), 6.05 (dq, 1H, J=13.8 Hz, J=6.6 Hz), 5.34 (q, 1H, J=6.6 Hz), 4.65 (ddd, 2H, J=13.2 Hz, J=6.6 Hz, 1.2 Hz), 3.79 (s, 6H), 1.62 (d, 3H, J=6.6 Hz).

[0184] Compound 154 7.88 (d, 1H, J=2.4 Hz), 7.62 (d, 1H, J=8.4 Hz), 7.37 (dd, 1H, J=3.0 Hz, J=8.4 Hz), 6.07 (t, 1H, J=7.2 Hz), 5.35 (q, 1H, J=7.2 Hz), 4.77 (d, 2H, J=7.2 Hz), 3.78 (s, 6H), 1.63 (d, 3H, J=7.2 Hz).

[0185] Compound 160 7.90 (d, 1H, J=2.4 Hz), 7.61 (d, 1H, J=8.4 Hz), 7.36 (dd, 1H, J=2.4 Hz, J=8.4 Hz), 5.36 (q, 1H, J=7.2 Hz), 4.01 (ddd, 2H, J=7.8 Hz, J=11.4 Hz, J=19.2 Hz), 3.78 (s, 6H), 1.63 (d, 3H, J=7.8 Hz), 1.11-1.18 (m, 1H), 0.55-0.59 (m, 2H), 0.27-0.30 (m, 2H).

[0186] Compound 164 7.91 (dd, 1H, J=1.2 Hz, J=2.4 Hz), 7.61 (d, 1H, J=8.4 Hz), 7.36 (dd, 1H, J=2.4 Hz, J=7.8 Hz), 5.36 (dq, 1H, J=1.2 Hz, J=7.2 Hz), 4.50 (ddd, J=3.0 Hz, J=4.8 Hz, J=12.0 Hz), 4.04 (ddd, 1H, J=5.4 Hz, J=12.0 Hz, J=27.0 Hz), 3.78 (s, 6H), 3.74-3.78 (m, 1H), 3.19-3.25 (m, 1H), 2.84 (dt, J=7.2 Hz, J=4.2 Hz), 2.65 (ddd, J=3.0 Hz, J=4.8 Hz, J=22.2 Hz), 1.65 (d, 3H, J=6.6 Hz).

[0187] Compound 166 7.92 (dd, 1H, J=3.0 Hz, J=22.8 Hz), 7.61 (d, 1H, J=9.0 Hz), 7.37 (dd, 1H, J=2.4 Hz, J=8.4 Hz), 5.35-5.41 (m, 1H), 4.31-4.35 (m, 1H), 4.19-4.27 (m, 1H), 4.14-4.35 (m, 1H), 4.02-4.07 (m, 1H), 3.78 (s, 6H), 3.75-3.79 (m, 1H), 1.64 (d, 3H, J=7.2 Hz), 1.41 (d, 3H, J=6.0 Hz), 1.33 (d, 3H, J=10.2 Hz).

[0188] Compound 221 8.07 (d, 1H, J=7.8 Hz), 7.43 (d, 1H, J=9.0 Hz), 4.90 (s, 2H), 4.46 (t, 2H, J=6.0 Hz), 3.78 (s, 6H), 3.71 (t, 2H, J=6.0 Hz).

[0189] Compound 222 8.05 (d, 1H, J=7.8 Hz), 7.43 (d, 1H, J=9.0 Hz), 4.85 (s, 2H), 4.37 (t, 2H, J=6.0 Hz), 3.78 (s, 6H), 3.61 (t, 2H, J=6.0 Hz), 2.14 (pent, 2H, J=6.0 Hz).

[0190] Compound 225 8.05 (d, 1H, J=7.8 Hz), 7.43 (d, 1H, J=8.4 Hz), 4.85 (s, 2H), 4.23-4.26 (m, 2H), 3.78 (s, 6H), 3.55-3.59 (m, 2H), 1.82-1.87 (m, 4H).

[0191] Compound 241 8.06 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.0 Hz), 4.86 (s, 2H), 4.03 (d, 2H, J=6.6 Hz), 3.78 (s, 6H), 1.16-1.18 (m, 1H), 0.58-0.61 (m, 2H), 0.29-0.31 (m, 2H).

[0192] Compound 245 8.07 (d, 1H, J=7.8 Hz), 7.43 (d, 1H, J=9.6 Hz), 4.90 (s, 2H), 4.55 (dd, 1H, J=2.4 Hz, J=12.0 Hz), 4.04 (dd, 1H, J=6.0 Hz, J=12.0 Hz), 3.78 (s, 6H), 3.23-3.25 (m, 1H), 2.86-2.88 (m, 1H), 2.66-2.68 (m, 1H).

[0193] Compound 246 8.07 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.0 Hz), 4.89 (s, 2H), 4.25-4.30 (m, 1H), 4.10-4.16 (m, 2H), 3.85-3.90 (m, 1H), 3.78 (s, 6H), 3.77-3.81 (m, 1H), 1.99-2.04 (m, 1H), 1.86-1.95 (m, 2H), 1.57-1.64 (m, 1H).

[0194] Compound 247 8.09 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.0 Hz), 4.89 (2d, 2H, J=16.2 Hz), 4.32-4.37 (m, 2H), 4.16-4.20 (m, 1H), 3.78 (s, 6H), 3.76-3.78 (m, 1H), 1.42 (s, 3H), 1.35 (s, 3H).

[0195] Compound 248 8.01 (d, 1H, J=7.2 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.32 (q, 1H, J=7.2 Hz), 4.24 (q, 2H, J=7.2 Hz), 3.78 (s, 6H), 1.61 (d, 3H, J=7.2 Hz), 1.26 (t, 3H, J=7.2 Hz).

[0196] Compound 249 8.02 (d, 1H, J=8.4 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.32 (q, 1H, J=7.2 Hz), 4.30 (q, 2H, J=7.2 Hz), 3.78 (s, 6H), 1.61 (d, 3H, J=6.6 Hz), 1.29 (t, 3H, J=7.2 Hz).

[0197] Compound 250 8.02 (d, 1H, J=7.8 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.32 (q, 1H, J=7.2 Hz), 4.23 (q, 2H, J=7.2 Hz), 3.78 (s, 6H), 1.61 (d, 3H, J=6.6 Hz), 1.29 (t, 3H, J=7.2 Hz).

[0198] Compound 264 8.02 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.38 (q, 1H, J=7.2 Hz), 4.63-4.69 (m, 1H), 4.55-4.61 (m, 1H), 4.36-4.49 (m, 2H), 3.78 (2s, 6H), 1.65 (d, 3H, J=7.2 Hz).

[0199] Compound 265 8.04 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.37 (q, 1H, J=7.2 Hz), 4.39-4.48 (m, 2H), 3.78 (2s, 6H), 3.71 (t, 2H, J=6.0 Hz), 1.65 (d, 3H, J=7.2 Hz).

[0200] Compound 266 8.03 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.37 (q, 1H, J=7.2 Hz), 4.39-4.48 (m, 2H), 3.78 (2s, 6H), 3.70 (t, 2H, J=6.0 Hz), 1.65 (d, 3H, J=7.8 Hz).

[0201] Compound 267 8.03 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=9.6 Hz), 5.37 (q, 1H, J=7.2 Hz), 4.40-4.47 (m, 2H), 3.78 (2s, 6H), 3.70 (t, 2H, J=5.4 Hz), 1.65 (d, 3H, J=7.2 Hz).

[0202] Compound 268 8.02 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=8.4 Hz), 5.33 (q, 1H, J=7.2 Hz), 4.35 (t, 2H, J=6.0 Hz), 3.78 (2s, 6H), 3.60 (t, 2H, J=6.0 Hz), 2.09-2.17 (m, 2H), 1.62 (d, 3H, J=6.6 Hz).

[0203] Compound 269 8.01 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.33 (q, 1H, J=7.2 Hz), 4.35 (t, 2H, J=6.0 Hz), 3.78 (2s, 6H), 3.60 (t, 2H, J=6.0 Hz), 2.09-2.17 (m, 2H), 1.62 (d, 3H, J=6.6 Hz).

[0204] Compound 270 8.01 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.33 (q, 1H, J=7.2 Hz), 4.35 (t, 2H, J=6.0 Hz), 3.78 (2s, 6H), 3.60 (t, 2H, J=6.0 Hz), 2.09-2.17 (m, 2H), 1.62 (d, 3H, J=6.6 Hz).

[0205] Compound 273 8.02 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.32 (q, 1H, J=7.2 Hz), 4.22 (t, 2H, J=6.0 Hz), 3.78 (2s, 6H), 3.56 (t, 2H, J=6.0 Hz), 1.83-1.85 (m, 4H), 1.62 (d, 3H, J=6.0 Hz).

[0206] Compound 281 8.01 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=9.0 Hz), 6.36 (dt, 1H, J=13.2 Hz, J=1.2 Hz), 6.05 (q, 1H, J=6.6 Hz), 5.33 (q, 1H, J=7.2 Hz), 4.65 (dt, 2H, J=13.2 Hz, 1.2 Hz), 3.79 (s, 6H), 1.62 (d, 3H, J=7.2 Hz).

[0207] Compound 283 8.01 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=8.4 Hz), 6.06 (t, 1H, J=6.6 Hz), 5.34 (q, 1H, J=7.2 Hz), 4.77 (dd, 2H, J=6.6 Hz, 1.2 Hz), 3.78 (s, 6H), 1.62 (d, 3H, J=7.2 Hz).

[0208] Compound 287 8.03 (d, 1H, J=7.2 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.37 (q, 1H, J=7.2 Hz), 4.74 (dq, 2H, J=15.0 Hz, J=2.4 Hz), 3.78 (2s, 6H), 1.86 (t, 3H, J=2.4 Hz), 1.63 (d, 3H, J=7.2 Hz).

[0209] Compound 289 7.97 (d, 1H, J=8.4 Hz), 7.40 (d, 1H, J=9.0 Hz), 7.31-7.37 (m, 5H), 5.39 (q, 2H, J=7.2 Hz), 5.21 (2d, 2H, J=12.6 Hz), 3.78 (s, 6H), 1.62 (d, 3H, J=7.2 Hz).

[0210] Compound 290 8.02 (d, 1H, J=7.8 Hz), 7.38-7.41 (m, 3H), 7.31-7.34 (m, 2H), 7.26-7.28 (m, 1H), 6.67 (d, 1H, J=15.6 Hz), 6.27 (dt, 1H, J=15.6 Hz, J=6.6 Hz), 5.37 (q, 1H, J=7.2 Hz), 4.83 (ddq, 2H, J=1.2 Hz, J=12.0 Hz, J=6.6 Hz), 3.77 (s, 3H), 3.76 (s, 3H), 1.64 (d, 3H, J=6.6 Hz).

[0211] Compound 291 8.03 (d, 1H, J=7.2 Hz), 7.41 (d, 1H, J=10.2 Hz), 5.34 (q, 1H, J=7.2 Hz), 4.01 (m, 2H), 3.78 (2s, 6H), 1.63 (d, 3H, J=7.2 Hz), 1.11-1.18 (m, 1H), 0.56-0.58 (m, 2H), 0.28-0.30 (m, 2H).

[0212] Compound 293 8.02 (d, 1H, J=7.8 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.34 (q, 1H, J=7.2 Hz), 4.03-4.10 (m, 2H), 3.78 (2s, 6H), 2.18-2.26 (m, 1H), 1.71-1.76 (m, 2H), 1.62 (d, 3H, J=7.2 Hz), 1.50-1.61 (m, 4H), 1.20-1.25 (m, 2H).

[0213] Compound 295 8.03 (d, 1H, J=7.2 Hz), 7.41 (d, 1H, J=9.6 Hz), 5.38 (q, 1H, J=7.2 Hz), 4.51 (ddd, 1H, J=3.6 Hz, J=6.0 Hz, J=12.6 Hz), 4.03 (ddd, 1H, J=6.0 Hz, J=12.6 Hz, J=29.4 Hz), 3.78 (2s, 6H), 3.19-3.25 (m, 1H), 2.85 (dt, 1H, J=7.8 Hz, J=4.2 Hz), 2.66 (ddd, 1H, J=3.0 Hz, J=4.8 Hz, J=22.2 Hz), 1.64 (dd, 3H, J=1.2 Hz, J=7.2 Hz), 1.11-1.18 (m, 1H), 0.56-0.58 (m, 2H), 0.28-0.30 (m, 2H).

[0214] Compound 296 8.04 (d, 1H, J=7.2 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.37 (dq, 1H, J=9.6 Hz, J=7.2 Hz), 4.24 (q, 1H, J=6.6 Hz), 4.10-4.16 (m, 3H), 3.83-3.87 (m, 1H), 3.78 (2s, 6H), 3.75-3.79 (m, 1H), 1.96-2.03 (m, 1H), 1.86-1.94 (m, 2H), 1.63 (dd, 3H, J=2.4 Hz, J=7.2 Hz).

[0215] Compound 297 8.05 (d, 1H, J=7.2 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.37 (dq, 1H, J=6.6 Hz, J=13.8 Hz), 4.31-4.36 (m, 1H), 4.18-4.28 (m, 1H), 4.10-4.36 (m, 1H), 4.02-4.07 (m, 1H), 3.78 (s, 6H), 3.74-3.79 (m, 1H), 1.63 (d, 3H, J=6.6 Hz), 1.41 (d, 3H, J=6.0 Hz), 1.33 (d, 3H, J=12.6 Hz).

[0216] Compound 298 8.05 (d, J=7.8 Hz, 1H), 7.36 (d, J=9.1 Hz, 1H), 5.66 (q, J=6.9 Hz, 1H), 4.13-4.07 (m, 2H), 4.02 (q, J=7.7 Hz, 1H), 3.98-3.92 (m, 1H), 3.76 (s, 3H), 3.75 (s, 3H), 1.58 (d, J=6.9 Hz, 3H), 1.25-1.22 (m, 2H).

[0217] Compound 299 8.00 (d, 1H, J=7.8 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.20 (dd, 1H, J=4.8 Hz, J=7.2 Hz), 4.21-4.27 (m, 2H), 3.78 (2s, 6H), 1.96-2.03 (m, 2H), 1.29 (t, 3H, J=7.2 Hz), 1.07 (t, 3H, J=7.2 Hz).

[0218] Compound 300 8.00 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.6 Hz), 5.25 (dd, 1H, J=4.8 Hz, J=7.8 Hz), 4.63-4.68 (m, 1H), 4.55-4.61 (m, 1H), 4.35-4.50 (m, 2H), 3.78 (2s, 6H), 2.00-2.08 (m, 2H), 1.08 (t, 3H, J=7.8 Hz).

[0219] Compound 301 8.01 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.25 (dd, 1H, J=4.8 Hz, J=7.8 Hz), 4.44-4.48 (m, 1H), 4.38-4.42 (m, 1H), 3.78 (2s, 6H), 3.70 (t, 2H, J=5.4 Hz), 1.99-2.08 (m, 2H), 1.09 (t, 3H, J=7.2 Hz).

[0220] Compound 302 8.00 (d, 1H, J=7.8 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.20 (dd, 1H, J=4.8 Hz, J=7.2 Hz), 4.35 (t, 2H, J=6.0 Hz), 3.78 (2s, 6H), 3.60 (t, 2H, J=6.0 Hz), 2.08-2.17 (m, 2H), 1.97-2.03 (m, 2H), 1.07 (t, 3H, J=7.2 Hz).

[0221] Compound 303 8.00 (d, 1H, J=8.4 Hz), 7.42 (d, 1H, J=9.0 Hz), 5.19 (dd, 1H, J=4.8 Hz, J=6.6 Hz), 4.22 (t, 2H, J=6.0 Hz), 3.78 (2s, 6H), 3.56 (t, 2H, J=6.0 Hz), 1.97-2.04 (m, 2H), 1.82-1.85 (m, 4H), 1.07 (t, 3H, J=7.2 Hz).

[0222] Compound 304 8.01 (d, 1H, J=8.4 Hz), 7.41 (d, 1H, J=9.0 Hz), 5.22 (dd, 1H, J=6.0 Hz, J=7.2 Hz), 4.22 (dq, 2H, J=7.8 Hz, J=10.8 Hz), 3.78 (2s, 6H), 1.97-2.07 (m, 2H), 1.11-1.17 (m, 1H), 1.08 (t, 3H, J=7.2 Hz), 0.55-0.59 (m, 2H), 0.26-0.31 (m, 2H).

[0223] Compound 305 7.99 (d, 1H, J=7.2 Hz), 7.42 (d, 1H, J=9.6 Hz), 5.09 (d, 1H, J=4.2 Hz), 4.20-4.28 (m, 2H), 3.78 (2s, 6H), 2.34-2.39 (m, 1H), 1.29 (t, 3H, J=7.2 Hz), 1.08 (d, 3H, J=6.6 Hz), 1.06 (d, 3H, J=6.6 Hz).

[0224] Compound 306 7.91 (d, 1H, J=7.8 Hz), 7.39 (d, 1H, J=9.0 Hz), 4.22 (q, 2H, J=7.2 Hz), 3.78 (s, 6H), 1.68 (s, 6H), 1.06 (t, 3H, J=7.2 Hz).

BIOMETRIC TEST EMBODIMENTS

Embodiment 15 Determination of herbicidal activity

[0225] Seeds of broadleaf weeds (zinnia and piemarker) or grassy weeds (green bristlegrass and barnyard grass) were respectively sown in a paper cup having a diameter of 7 cm and containing nutrient soil; after sowing, the seeds were covered with 1 cm of soil; the soil was pressed and watered, and then the seeds were cultivated in a greenhouse according to a conventional method; and stems and leaves were sprayed after 2-3 leaf stage of the weeds.

[0226] After the original medicinal acetone was dissolved, the test requires to use 1‰ of Tween 80 to stand in running water to prepare the solution to be tested with a required concentration. According to the design dose of the test, spray treatment was carried out on a track-type crop sprayer (designed and produced by British Engineer Research Ltd.) (spray pressure is 1.95 kg/cm.sup.2, spray volume is 500 L/hm.sup.2 and track speed is 1.48 km/h). The test was repeated for three times. The test material was treated and then placed in an operation hall. The medicinal liquid was naturally dried in the shade, and then was placed in a greenhouse and managed according to the conventional method. The response of the weeds to the drug was observed and recorded. After treatment, the control effects of the test drug on the weeds were visually inspected regularly, expressed by 0-100%. “0” represents no control effect and “100%” represents complete killing.

[0227] The test results show that the compounds of the formula I generally have high control effects on various weeds. Part of the test compounds, such as compounds 221, 222, 225, 241, 245, 246, 247, 248, 249, 250, 264, 265, 266, 267, 268, 269, 270, 273, 281, 283, 287, 289, 290, 291, 293, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304 and 305, have good control effects on zinnia at the application dose of 150 g a.i./hm.sup.2, and the control effects are 100%.

[0228] The test results show that the compounds of the formula I generally have high control effects on various weeds. Part of the test compounds, such as compounds 138, 160, 221, 222, 225, 241, 245, 246, 247, 248, 249, 250, 264, 265, 266, 267, 268, 269, 270, 273, 281, 283, 287, 289, 290, 291, 293, 295, 296, 297, 298, 300, 301, 302, 303, 304, 305 and 306, have good control effects on piemarker at the application dose of 150 g a.i./hm.sup.2, and the control effects are 100%.

[0229] The test results show that the compounds of the formula I generally have high control effects on various weeds. Part of the test compounds, such as compounds 117, 221, 222, 225, 241, 245, 246, 247, 248, 250, 264, 268, 273, 281, 283, 287, 291, 295, 296, 297 and 298, have good control effects on green bristlegrass at the application dose of 150 g a.i./hm.sup.2, and the control effects are not less than 80%.

[0230] The test results show that the compounds of the formula I generally have high control effects on various weeds. Part of the test compounds, such as compounds 221, 222, 225, 241, 245, 246, 247, 248, 249, 250, 264, 265, 266, 267, 268, 269, 270, 273, 281, 283, 287, 291, 293, 295, 296, 297, 298, 301 and 306, have good control effects on barnyard grass at the application dose of 150 g a.i./hm.sup.2, and the control effects are not less than 90%.

##STR00382##

[0231] According to the above test methods, part of compounds of formula I and the following compound KC.sub.1 specifically disclosed in patent CN1341105A (compound No. 30 in Table 3 of the patent description) are selected to conduct parallel tests for herbicidal activity under the application doses of 37.5 g a.i./hm.sup.2 and 9.375 g a.i./hm.sup.2. The results are shown in Table 2.

TABLE-US-00002 TABLE 2 Herbicidal Activity of Part of Compounds of Formula (I) (after emergence, control effect %) Dose g Green Barnyard Compound a.i./hm.sup.2 Zinnia Piemarker Bristlegrass Grass 248 (rac.) 37.5 90 100 95 100 9.375 60 90 70 95 249 (R) 37.5 70 100 80 55 9.375 50 65 35 30 250 (S) 37.5 98 100 100 90 9.375 70 98 100 50 KC.sub.1 37.5 60 100 25 25 9.375 50 55 10 0

[0232] According to the above test methods, part of compounds of formula I and the following compound KC.sub.1 (compound No. 30 in Table 3 of the patent description) and KC.sub.2 (R body, compound No. 12 in Table 3 of the patent description) specifically disclosed in patent CN1341105A are selected to conduct parallel tests for herbicidal activity of zinnia, piemarker, green bristlegrass and barnyard grass. Results are shown in Table 3 to Table 6.

TABLE-US-00003 TABLE 3 Parallel Comparison of Herbicidal Activity of Part of Compounds of Formula (I) for Zinnia(after emergence, control effect %) Compound 221 222 225 241 245 246 247 248 250 264 266 267 268 269 Dose 9.375 100 100 100 100 100 95 100 100 95 100 100 100 100 95 g a.i./hm.sup.2 2.34 85 100 95 100 95 95 100 95 80 90 85 85 85 80 Compound 270 281 283 287 291 293 295 296 297 298 302 303 304 KC.sub.1 Dose 9.375 100 100 100 100 100 100 100 100 100 100 100 100 100 50 g a.i./hm.sup.2 2.34 90 90 100 80 85 90 90 90 95 90 90 85 80 / Note: “/” indicates no test.

TABLE-US-00004 TABLE 4 Parallel Comparison of Herbicidal Activity of Part of Compounds of Formula (I) for Piemarker(after emergence, control effect %) Compound 221 225 241 248 250 265 267 270 273 291 293 297 298 299 KC.sub.1 Dose 9.375 100 100 100 100 100 100 100 100 100 100 100 100 100 100 55 g a.i./hm.sup.2 2.34 85 85 98 90 85 90 90 85 90 85 85 85 85 85 / Note: “/” indicates no test.

TABLE-US-00005 TABLE 5 Parallel Comparison of Herbicidal Activity of Part of Compounds of Formula (I) for Green Bristlegrass (after emergence, control effect %) Compound 221 222 225 241 245 246 247 248 250 281 283 287 KC.sub.1 KC.sub.2 Dose 37.5 90 90 90 100 90 90 90 85 90 90 85 70 25 50 g a.i./hm.sup.2 9.375 80 60 80 80 70 80 60 60 70 60 50 50 10 20

TABLE-US-00006 TABLE 6 Parallel Comparison of Herbicidal Activity of Part of Compounds of Formula (I) for Barnyard Grass (after emergence, control effect %) Compound 221 225 241 245 246 248 250 291 KC.sub.1 KC.sub.2 Dose 37.5 100 100 98 98 98 100 100 100 25 90 g a.i./hm.sup.2 9.375 98 95 95 95 95 90 90 90 0 75