Unsaturated hydrocarbon pyrimidine thioether compounds and preparation method and application thereof

Abstract

The present invention discloses unsaturated hydrocarbon pyrimidine thioether compounds of formula (I) and preparation method and application thereof, the compounds of formula (I) exhibit high insecticidal and acaricidal activity against adults, larvae and eggs of harmful mites and insects in the agriculture, civil use and animal technology fields, meanwhile, the compounds also exhibit good bactericidal activity, and can be widely applied as an insecticide, an acaricide and/or a bactericide in agriculture or other fields ##STR00001##

Claims

1. A substituted pyrimidine thioether compound as shown in formula (I): ##STR00671## in formula (I): R.sub.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.12 alkyl, C.sub.3-C.sub.12 cycloalkyl, halogenated C.sub.1-C.sub.12 alkyl and C.sub.1-C.sub.12 alkoxy; R.sub.2 is selected from the group consisting of hydrogen, halogen, nitro, cyano, C.sub.1-C.sub.12 alkyl, halogenated C.sub.1-C.sub.12 alkyl and C.sub.1-C.sub.12 alkoxy; R.sub.3 is selected from the group consisting of C.sub.2-C.sub.12 alkenyl, halogenated C.sub.2-C.sub.12 alkenyl, C.sub.2-C.sub.12 alkynyl, halogenated C.sub.2-C.sub.12 alkynyl and C.sub.3-C.sub.12 cycloalkenyl; and Q is a group selected from Q.sub.1-Q.sub.7, Q.sub.10, Q.sub.11, Q.sub.13 and Q.sub.14: ##STR00672## ##STR00673##

2. The substituted pyrimidine thioether compound as claimed in claim 1, wherein R.sub.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.8 cycloalkyl, halogenated C.sub.1-C.sub.6 alkyl and C.sub.1-C.sub.6 alkoxy; R.sub.2 is selected from the group consisting of hydrogen, halogen, nitro, cyano, C.sub.1-C.sub.6 alkyl, halogenated C.sub.1-C.sub.6 alkyl and C.sub.1-C.sub.6 alkoxy; R.sub.3 is selected from the group consisting of C.sub.2-C.sub.6 alkenyl, halogenated C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, halogenated C.sub.2-C.sub.6 alkynyl and C.sub.3-C.sub.6 cycloalkenyl.

3. The substituted pyrimidine thioether compound as claimed in claim 2, wherein R.sub.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.4 alkyl, C.sub.3-C.sub.6 cycloalkyl, halogenated C.sub.1-C.sub.4 alkyl and C.sub.1-C.sub.4 alkoxy; R.sub.2 is selected from the group consisting of hydrogen, halogen, nitro, cyano, C.sub.1-C.sub.4 alkyl, halogenated C.sub.1-C.sub.4 alkyl and C.sub.1-C.sub.4 alkoxy; R.sub.3 is selected from the group consisting of C.sub.2-C.sub.6 alkenyl, halogenated C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, halogenated C.sub.2-C.sub.6 alkynyl and C.sub.3-C.sub.6 cycloalkenyl; and Q is a group selected from Q.sub.1-Q.sub.7.

4. The substituted pyrimidine thioether compound as claimed in claim 3, wherein R.sub.1 is hydrogen, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, n-butyl, isobutyl, tert-butyl, monofluoromethyl, monochloromethyl, difluoromethyl, trifluoromethyl or trifluoroethyl; R.sub.2 is hydrogen, fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, methoxy, ethoxy or trifluoroethoxy; R.sub.3 is CH.sub.2═CHCH.sub.2, (CH.sub.3).sub.2C═CHCH.sub.2, CH.sub.3CH═CHCH.sub.2, CHCl═CHCH.sub.2, CH.sub.2═CClCH.sub.2, CHCl═CClCH.sub.2, CCl.sub.2═CHCH.sub.2, CCl.sub.2═CClCH.sub.2, CF.sub.2═CFCH.sub.2, CF.sub.2═CFCH.sub.2CH.sub.2, CH≡CCH.sub.2 or CH.sub.3C≡CCH.sub.2; Q is a group selected from Q.sub.1-Q.sub.6.

5. The substituted pyrimidine thioether compound as claimed in claim 4, wherein R.sub.1 is methyl, ethyl, n-propyl, isopropyl, cyclopropyl, difluoromethyl or trifluoromethyl; R.sub.2 is hydrogen, chlorine, nitro, methyl or n-butyl; R.sub.3 is CH.sub.2═CHCH.sub.2, (CH.sub.3).sub.2C═CHCH.sub.2, CH.sub.3CH═CHCH.sub.2, CHCl═CHCH.sub.2, CH.sub.2═CClCH.sub.2, CHCl═CClCH.sub.2, CCl.sub.2═CHCH.sub.2, CCl.sub.2═CClCH.sub.2, CF.sub.2═CFCH.sub.2CH.sub.2, CH≡CCH.sub.2 or CH.sub.3C≡CCH.sub.2; Q is a group selected from Q.sub.1-Q.sub.4.

6. A preparation method of the substituted pyrimidine thioether compound represented by formula (I) as claimed in claim 1, where Q in the compound of formula (I) is selected from any one of Q.sub.1, Q.sub.2, Q.sub.3, Q.sub.6, Q.sub.7, Q.sub.10, Q.sub.11 and Q.sub.13, the method comprises: reacting a hydroxyl-containing pyrimidine compound of formula (III) and benzyl halide of formula (IV) in the presence of an alkaline material and an organic solvent at a temperature ranging from 20 to 100° C. for 0.5 to 20 hours; performing separation and purification to obtain the corresponding substituted pyrimidine thioether compound of formula (I); wherein a molar ratio of the compound of formula (III) to the compound of formula (IV) ranges from 1:1 to 1:1.1; ##STR00674## in formula (III) or formula (IV), R.sub.1, R.sub.2, R.sub.3 and Q have the same definitions with that of formula (I), X is a leaving group selected between chlorine and bromine; where Q in the compound of formula (I) is selected from Q.sub.4, Q.sub.5 or Q.sub.14, the method further comprises: reacting the compound of formula (I) in which Q is respectively Q.sub.2, Q.sub.3 or Q.sub.13 with a methylamine aqueous solution to obtain the compound of formula (I) in which Q is Q.sub.4, Q.sub.5 or Q.sub.14, respectively; wherein a mass concentration of the methylamine aqueous solution is between 20% and 60%; a molar ratio of the compound of formula (I) in which Q is Q.sub.2, Q.sub.3 or Q.sub.13 to methylamine in the methylamine aqueous solution ranges from 1:5 to 1:10.

7. The method as claimed in claim 6, wherein the organic solvent is tetrahydrofuran, cyclopentyl methyl ether acetonitrile, xylene, chlorobenzene, DMF, N,N-dimethylacetamide, DMSO, acetone, butanone, methyl isobutyl ketone or methyl tert-butyl ether.

8. The method as claimed in claim 6, wherein the alkaline material is selected from potassium hydroxide, sodium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, trisodium phosphate, disodium hydrogen phosphate, tripotassium phosphate, dipotassium hydrogen phosphate, triethylamine, pyridine, DBU, DMAP, sodium methoxide, sodium ethoxide, sodium hydride, potassium t-butoxide or sodium t-butoxide.

9. The application of the substituted pyrimidine thioether compound of formula (I) as claimed in claim 1 as an insecticide, an acaricide and/or a bactericide, comprising applying the substituted pyrimidine thioether compound of formula (I) at where in need of.

10. An insecticidal and/or bactericidal composition, wherein the composition comprises the substituted pyrimidine thioether compound of formula (I) as claimed in claim 1 and agriculturally acceptable carriers, wherein the mass fraction of the substituted pyrimidine thioether compound of formula (I) is ranging from 1% to 90%.

Description

SPECIFIC EMBODIMENTS

(1) The present invention is further illustrated below with reference to specific embodiments, but the present invention is not limited to these specific embodiments. Those skilled in the art should recognize that the present invention encompasses all alternatives, modifications and equivalents that may be included within the scope of the claims.

Example 1

Synthesis of Compound 81

(1) Synthesis of Intermediate 3a

(2) ##STR00664##

(3) To a solution of 18.24 g (0.24 mol) of thiourea in 150 mL of methanol, a solution of 26.4 g (0.48 mol) of sodium methoxide in methanol was slowly added dropwise with stirring at room temperature, and stirring was continued at room temperature for 2 h. Then, 26 g (0.2 mol) of intermediate, ethyl acetoacetate, was added dropwise to the above solution, and the reaction was stirred at reflux for 6-8 h. After the reaction was detected by TLC, the solvent was evaporated under reduced pressure, the resulting mixture was adjusted to pH 5-6 with hydrochloric acid to precipitate a solid, and then was filtered to a white solid, and after drying, 27 g of the white solid was obtained. The yield was 95%.

(2) Synthesis of Intermediate 5a

(4) ##STR00665##

(5) 1.42 g (0.01 mol) of 3a was dissolved in 15 mL of N,N-dimethylformamide, and 1.51 g of potassium carbonate was added thereto, and the mixture was stirred for 0.5 h and then of 1.9 g of 4a was added dropwise thereto, and then the temperature was raised to 60° C., and the reaction was stirred for 4 hours. After the reaction was detected by TLC, the solvent was evaporated under reduced pressure, and water was added, and pH was adjusted to 5-6 with hydrochloric acid to precipitate a solid, which was filtered to give a white solid, and after drying, 2.3 g of the white solid was obtained. The yield was 92%.

(3) Synthesis of Compound 81

(6) 1.25 g (0.005 mol) of 5a was dissolved in 10 ml of N, N-dimethylformamide, and 0.83 g of potassium carbonate was added thereto, and the mixture was stirred for 0.5 h, and 1.26 g of 6a was added in portions, then, the mixture was heated to 80° C., and stirred for 8 hours. After the reaction was detected by TLC, the reaction solution was poured into 50 ml of saturated brine, and extracted with three portions of ethyl acetate (100 ml) and dried. After desolvation, it was purified by column chromatography eluting with petroleum ether: ethyl acetate 1000:1˜1400 to yield 1.95 g of oily product.

(7) ##STR00666##

Example 2

Synthesis of the Compound 258

(1) Synthesis of Intermediate 3c

(8) 1.78 g (0.01 mol) of 1c was dissolved in 15 ml of N,N-dimethylformamide, and 1.51 g of potassium carbonate was added thereto, and the mixture was stirred for 0.5 h. and 1.2 g of 2c was added dropwise thereto, then, the temperature was raised to 60° C., and the reaction was stirred for 4 hours. After the reaction was detected by TLC, the solvent was evaporated under reduced pressure, and water was added, and pH was adjusted to 5-6 with hydrochloric acid to precipitate a solid, which was filtered to give a white solid, and after drying, 2.2 g of the white solid was obtained. The yield was 86.9%.

(9) ##STR00667##

(2) Synthesis of Compound 258

(10) 1.3 g (0.005 mol) of 3c was dissolved in 10 ml of N,N-dimethylfomamide, and 0.83 g of potassium carbonate was added thereto, and the mixture was stirred for 0.5 and 1:45 g of 2b was added in portions, then, the mixture was heated to 80° C., and stirred for 8 hours. After the reaction was detected by TLC, the reaction solution was poured into 50 ml of saturated brine, and extracted with three portions of ethyl acetate (100 ml) and dried. After desolvation, it was purified by column chromatography eluting with petroleum ether: ethyl acetate 1000:1-300 to yield 1.86 g of oily product.

(11) ##STR00668##

Example 3

Synthesis of the Compound 315

(12) 1.35 g (0.005 mol) of 1 b was dissolved in 10 ml of N,N-dimethylformamide, and 0.83 g of potassium carbonate was added thereto, and the mixture was stirred for 0.5 and 1:45 g of 2b was added in portions, then, the mixture was heated to 80° C., and stirred for 8 hours. After the reaction was detected by TLC, the reaction solution was poured into 50 ml of saturated brine, and extracted with three portions of ethyl acetate (100 ml) and dried. After desolvation, it was purified by column chromatography eluting with petroleum ether: ethyl acetate 1000:1˜300 to yield 1.92 g of oily product.

(13) ##STR00669##

Example 4

Synthesis of the Compound 420

(14) 1.0 g (0.002 mol) of 1 b was dissolved in 30 ml of ethanol, and 0.85 g of a 40% aqueous solution of methylamine was added thereto, then the mixture was heated to reflux temperature and reacted, the reaction was stirred for 8 hours. After the reaction was detected by TLC and desolvation, it was purified by column chromatography eluting with petroleum ether: ethyl acetate 1000:1˜300 to yield 0.86 g of oily product.

(15) ##STR00670##

(16) The other compounds of the present invention can be prepared with reference to the examples above, and here is no more pleonasm.

(17) Nuclear magnetic data of partial compounds:

(18) Compound 1 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.31 (s, 3H, CH.sub.3), 3.61 (s, 3H, CH.sub.3), 3.77-3.78 (d, 2H, CH.sub.2), 3.79 (s, 3H, CH.sub.3), 5.08-5.34 (m, 2H), 5.27 (s, 2H, CH.sub.2), 5.90-6.05 (m, 1H), 6.40 (s, 1H, pyrimidyl-1H), 7.14-7.47 (m, 4H, Ar—H), 7.66 (s, 1H, CH).

(19) Compound 3 .sup.1HNMR (400 MHz, CDCl.sub.3): 3.71 (s, 3H, CH.sub.3), 3.84 (s, 5H, CH.sub.3, CH.sub.2), 5.17 (d 1H, CH.sub.2), 5.36 (d, 1H, CH.sub.2), 5.40 (s, 2H, CH.sub.2), 5.95-6.03 (m, 1H, CH), 6.71 (s, 1H, pyrimidyl-H), 7.23 (d, 1H, Ar—H), 7.38-7.40 (m, 2H, Ar—H), 7.52 (d, 1H, Ar—H).

(20) Compound 9 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.59 (s, 3H, CH.sub.3), 3.80-3.84 (d, 2H, CH.sub.2), 3.79 (s, 3H, CH.sub.3), 5.12-5.30 (m, 2H, CH.sub.2), 5.34 (s, 2H, CH.sub.2), 5.91-6.01 (m, 1H) 6.73-6.98 (m, 1H, CHF2), 6.81 (s, 1H, pyrimidyl-1H), 7.12-7.50 (m, 4H, Ar—H), 7.64 (s, 1H, CH).

(21) Compound 10 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.62 (s, 3H, CH.sub.3), 3.82 (s, 3H, CH.sub.3), 3.91-3.93 (d, 2H, CH.sub.2), 5.12-5.14 (d, 1H), 5.36 (s, 2H, CH.sub.2), 5.31-5.36 (m, 1H), 5.90-6.00 (m, 1H), 7.05 (s, 1H, pyrimidyl-H), 7.09-7.46 (m, 4H, Ar—H), 7.66 (s, 1H, CH).

(22) Compound 19 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.70-1.71 (d, 6H, 2CH.sub.3), 3.59 (s, 3H, CH.sub.3), 3.80-3.81 (d, 2H, CH.sub.2), 3.80 (s, 3H, CH.sub.3), 5.33-5.35 (m, 1H), 5.37 (s, 2H, CH.sub.2), 7.06 (s, 1H, pyrimidyl-H), 7.14-7.47 (m, 4H, Ar—H), 7.65 (s, 1H, CH).

(23) Compound 35 .sup.1HMNR (400 MHz, DMSO) δ (ppm): 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 4.14 (s2H, CH.sub.2), 5.36 (s, 2H, CH.sub.2), 5.38-5.39 (d, 1H, CH.sub.2), 5.62 (d, 1H, CH.sub.2), 5.59 (d, 1H), 7.09 (s, 1H, pyrimidyl-H), 7.14-7.53 (m, 4H, Ar—H), 7.65 (s, 1H, CH).

(24) Compound 41 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.59 (s, 3H, CH.sub.3), 3.80 (s, 3H, CH.sub.3), 4.29 (s2H, CH.sub.2), 5.33 (s, 2H, CH.sub.2), 5.21 (d, 1H), 5.61 (d, 1H), 5.64 (d, 1H, CH.sub.2), 6.73-7.02 (m, 1H, CHF.sub.2), 6.89 (s, 1H, pyrimidyl-H), 7.13-7.51 (m, 4H, Ar—H), 7.64 (s, 1H, CH).

(25) Compound 43 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.15-1.19 (m, 3H, CH.sub.3), 2.57-2.63 (m, 2H, CH.sub.2), 3.59 (s, 3H, CH.sub.3), 3.80 (s, 3H, CH.sub.3), 4.14 (s2H, CH.sub.2), 5.24 (s, 2H, CH.sub.2), 5.33 (d, 1H), 5.57 (d, 1H), 6.47 (s, 1H, pyrimidyl-H), 7.11; 7.65 (s, 1H, CH).

(26) Compound 49 .sup.1HNMR (400 MHz, CDCl.sub.3) 2.33 (s, 3H, CH.sub.3), 3.70 (s, 0.34*3H, CH.sub.3), 3.71 (s, 0.66*3H, CH.sub.3), 3.76 (d, 0.66*2H, CH.sub.2), 3.94 (d, 0.34*2H, CH.sub.2), 3.82 (s, 0.34*3H, CH.sub.3), 3.83 (s, 0.66*3H, CH.sub.3), 5.32 (s, 0.34*2H, CH.sub.2), 5.33 (s, 0.66*2H, CH.sub.2), 6.01-6.10 (m, 1H), 6.14 (d, 034*2H, CH.sub.2), 6.20 (d, 0.66*2H, CH.sub.2), 6.28 (s, 0.34*1H, pyrimidyl-H), 6.29 (s, 0.66*1H, pyrimidyl-H), 7.21 (t, 1H, Ar—H), 7.37 (q, 2H, Ar—H), 7.50 (1, 1H, Ar—H), 7.59 (s, 0.34*1H, CH), 7.59 (s, 0.66*1H, CH).

(27) Compound 50 .sup.1HNMR (400 Mhz, CDCl.sub.3) 3.71 (s, 0.5*3H, CH.sub.3), 3.72 (s, 0.5*3H, CH.sub.3), 3.79 (d, 0.5*2H, CH.sub.2), 3.82 (d, 0.5*2H, CH.sub.2), 3.82 (s, 0.5*3H, CH.sub.3), 3.83 (s, 0.5*CH.sub.3), 3.83 (s, 0.5*3H, CH.sub.3), 5.40 (s, 0.5*2H, CH.sub.2), 5.41 (s, 0.5*2H, CH.sub.2), 6.03-6.10 (m, 1H), 6.19 (d, 0.5*2H, CH.sub.2), 6.27 (d, 0.5*2H, CH.sub.2), 6.70 (s, 1H, pyrimidyl-H), 7.23-7.25 (m, 1H, Ar—H), 7.37-7.40 (m, 2H, Ar—H), 7.51-7.53 (m, 1H, Ar—H), 7.61 (s, 0.5*1H, CH), 7.62 (s, 0.5*1H, CH).

(28) Compound 51 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 3.86-3.95 (m, 2H, CH.sub.2), 5.36 (s, 2H, C.sub.2), 6.04-6.17 (m, 1H, CH), 6.47-6.54 (m, 1H, CH), 7.07 (s, 1H, pyrimidyl-1-H), 7.13-7.52 (m, 4H, Ar—H), 7.66 (s, 1H, CH).

(29) Compound 52 .sup.1HNMR (400 MHz, CDCl.sub.3): 1.26 (t, 3H, CH.sub.3), 2.68 (q, 2H, CH.sub.2), 3.71 (s, 3H, CH.sub.3), 3.82 (s, 3H, CH.sub.3), 4.09 (s, 2H, CH.sub.2), 5.40 (s, 2H, CH.sub.2), 5.30 (s, 1H, CH.sub.2), 5.55 (s, 1H, CH.sub.2), 6.75 (s, 1H, pyrimidyl-H), 7.20-7.22 (m, 1H, Ar—H), 7.35-7.38 (m, 2H, Ar—H), 7.52-7.54 (t, 1H, Ar—H).

(30) Compound 55 .sup.1HNMR (400 MHz, CDCl.sub.3): 0.89-1.12 (m, 4H, cyclopropyl-2CH.sub.2), 1.84-1.89 (m, 1H, cyclopropyl-CH), 3.71 (s, 0.5*3H, CH.sub.3), 3.72 (s, 0.5*3H, CH.sub.3), 3.72 (d, 0.5*2H, CH.sub.2), 3.83 (s, 0.5*3H, CH.sub.3), 3.84 (s, 0.5*3H, CH.sub.3), 3.89 (d, 0.5*2H, CH.sub.2), 5.31 (s, 2H, CH.sub.2), 6.01-6.09 (m, 1H), 6.14 (d, 0.5*2H, CH.sub.2), 6.20 (d, 0.5*2H, CH.sub.2), 6.28 (s, 0.5*1H, pyrimidyl-H), 6.29 (s, 0.5*1H, pyrimidyl-H), 7.21 (t, 1H, Ar—H), 7.36 (t, 2H, Ar—H), 7.50 (t, Ar—H), 7.59 (s, 0.5*1H, CH), 7.60 (s, 0.5*1H, CH).

(31) Compound 57 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 3.84-3.85 (m, 2H, CH.sub.2), 5.34 (s, 2H, CH.sub.2), 6.06-6.15 (m, 1H, CH), 6.45-6.54 (m, 1H, CH), 6.71-7.03 (m, 1H, CHF.sub.2), 6.78 (s, 1H, pyrimidyl-H), 7.13-7.51 (n, 4H, Ar—H), 7.64 (s, 1H, CH).

(32) Compound 65 .sup.1HNMR (400 MHz, CDCl.sub.3): 2.39 (s, 3H, CH.sub.3), 3.71 (s, 3H, CH.sub.3), 3.83 (s, 3H, CH.sub.3), 3.85 (d, 2H, CH.sub.2), 5.32 (s, 2H, CH.sub.2), 6.11 (t, 1H, CH), 6.29 (s, 1H, pyrimidyl-H), 7.20-7.22 (m, 1H, Ar—H), 7.35-7.38 (m, 2H, Ar—H), 7.47-7.49 (n, 1H, Ar—H), 7.59 (s, H, CH).

(33) Compound 66 .sup.1HNMR (400 MHz, CDCl.sub.3): 3.71 (s, 3H, CH.sub.3), 3.84 (s, 3H, CH.sub.3), 3.88 (d, 2H, CH.sub.2), 5.38 (s, 2H, CH.sub.2), 6.11 (t, 1H, CH), 6.70 (s, 1H, pyrimidyl-H), 7.21-7.23 (t, 1H, Ar—H), 7.37-7.40 (m, 2H, Ar—H), 7.49-7.51 (m, 1H, Ar—H), 7.60 (s, 1H, CH).

(34) Compound 67 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.59 (s, 3H, CH.sub.3), 3.81 (s, 3H, CH.sub.3), 3.84-3.94 (d2H, CH.sub.2), 5.37 (s, 2H, CH.sub.2), 6.05-6.16 (m, 1H, CH), 7.07 (s, 1H, pyrimidyl-H), 7.10-7.52 (m, 4H, Ar—H), 7.65 (s, 1H, CH).

(35) Compound 68 .sup.1HNMR (400 MHz, CDCl.sub.3): 1.27 (t, 3H, CH.sub.3), 2.67 (q, 2H, CH.sub.2), 3.86 (d, 2H, CH.sub.2), 3.71; s, 3H, CH.sub.3), 3.84 (s, 3H, CH.sub.3), 5.32 (s, 2H, CH.sub.2), 6.13 (1H, CH), 6.29 (s, 1H, pyrimidyl-H), 7.22 (t, 1H, Ar—H), 7.37 (q, 2H, Ar—H), 7.50 (t, 1H, Ar—H).

(36) Compound 69 .sup.1HNMR (400 MHz, CDCl.sub.3): 0.98 (t, 3H, CH.sub.3), 1.69-1.76 (m, 2H, CH.sub.2), 0.98 (t, 2H, CH.sub.2), 3.71 (s, 3H, CH.sub.3), 3.84 (s, 3H, CH.sub.3), 3.86 (d, 2H, CH.sub.2), 5.32 (s, 2H, CH.sub.2), 6.13 (t, 1H, CH), 6.28 (s, 1H, pyrimidyl-H) 7.21 (t, 1H, Ar—H), 7.37 (1, 2H, Ar—H), 7.50 (t, 1H, AR—H), 7.59 (s, H, CH).

(37) Compound 71 .sup.1HNMR (400 MHz, CDCl.sub.3): 1.00-1.12 (m, 4H, cyclopropyl-2CH.sub.2), 1.87-1.90 (m, 1H, cyclopropyl-CH), 3.71 (s, 3H, CH.sub.3), 3.80 (d, 2H, CH.sub.2), 3.84 (s, 3H, CH.sub.3), 5.30 (s, 2H, CH.sub.2), 6.09 (t, 1H, CH), 6.28 (s, 1H, pyrimidyl-H), 7.19-7.21 (m, 1H, Ar—H), 7.35-7.38 (m, 2H, Ar—H), 7.48-7.50 (m, H, Ar—H), 7.59 (s, H, CH).

(38) Compound 81 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.31 (s, 3H, CH.sub.3), 2.63-2.78 (m, 2H, CH.sub.2), 3.29-3.34 (m, 2H, CH.sub.2), 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.28 (s, 2H, CH.sub.2), 6.47 (s, 1H, pyrimidyl-H), 7.11-7.44 (m, 4H, Ar—H), 7.63 (s, 1H, CH).

(39) Compound 90 .sup.1HNMR (400 MHz, CDCl.sub.3): 3.72 (s, 3H, CH.sub.3), 3.85 (s, 3H, CH.sub.3), 4.14 (s, 2H, CH.sub.2), 5.40 (s, 2H, CH.sub.2), 6.61 (s, 1H, CH), 6.75 (s, 1H, pyrimidyl-H), 7.24 (d, 1H, Ar—H), 7.36-7.40 (n, 2H, Ar—H), 7.52 (d, 1H, Ar—H), 7.62 (s, 1H, CH).

(40) Compound 114 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.73-2.81 (n, 2H, CH.sub.2), 3.30-3.34 (m, 2H, CH.sub.2), 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.33 (s, 2H, CH.sub.2), 6.71-6.98 (m, 1H, CHF.sub.2), 6.83 (s, 1H, pyrimidyl-H), 7.13-7.49 (m, 4H, Ar—H), 7.63 (s, 1H, CH).

(41) Compound 115 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.72-2.82 (m, 2H, CH.sub.2), 3.29-3.34 (m, 2H, CH.sub.2) 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.28 (s, 2H, CH.sub.2), 6.63 (s, 1H, pyrimidyl-H), 7.12-7.46 (m, 4H, Ar—H), 7.67 (s, 1H, CH).

(42) Compound 116 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.13-1.20 (m, 3H, CH.sub.3), 2.57-2.62 (m, 2H, CH.sub.2, 2.71-2.80 (m, 2H, Ch.sub.2), 3.25-3.29 (m, 2H, CH.sub.3), 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.24 (s, 2H, CH.sub.2), 6.45 (s, 1H, pyrimidyl-H), 7.12-7.45 (m, 4H, Ar—H), 7.63 (s, 1H, CH).

(43) Compound 117 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.86-0.90 (m, 3H, CH.sub.3), 1.62-1.71 (m, 2H, CH.sub.2), 2.51-2.57 (m, 2H, CH.sub.2), 2.72-2.79 (m, 2H, CH.sub.2), 3.25-3.28 (m, 2H, CH.sub.2), 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.23 (s, 2H, CH.sub.2), 6.45 (s, 1H, pyrimidyl-H), 7.11-7.46 (m, 4H, Ar—H), 7.63 (s, 1H, CH).

(44) Compound 118 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.17-1.19 (d, 6H, CH.sub.3), 2.50-2.52 (m, H, CH), 2.72-2.83 (m, 2H, CH.sub.2), 3.26-3.29 (m, 2H, CH.sub.2), 3.58 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.23 (s, 2H, CH.sub.2), 6.45 (s, 1H, pyrimidyl-H), 7.11-7.47 (m, 4H, Ar—H), 7.63 (s, 1H, CH).

(45) Compound 119 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.98-0.99 (m, 4H, cyclopropyl-2CH.sub.2), 1.98-2.01 (m, H, CH), 2.69-2.75 (m, 2H, CH.sub.2), 3.20-3.23 (m, 2H, CH.sub.2), 3.59 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.21 (s, 2H, CH.sub.2), 6.53 (s, 1H, pyrimidyl-H), 7.11-7.63 (m, 4H, Ar—H), 7.67 (s, 1H, CH).

(46) Compound 127 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.98 (s, 3H, CH.sub.3), 2.31 (s, 3H, CH.sub.3), 2.69-2.77 (m, 2H, CH.sub.2), 3.22-3.26 (m, 2H, CH.sub.2), 3.58 (s, 3H, CH.sub.3), 3.79 (s, 3H, CH.sub.3), 5.24 (s, 2H, CH.sub.2), 7.12-7.51 (in, 4H, Ar—H), 7.62 (s, 1H, CH).

(47) Compound 128 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.83-0.91 (m, 3H, CH.sub.3) 1.27-1.42 (m, 4H, 2CH.sub.2), 2.37 (s, 3H, CH.sub.3), 2.45-2.51 (m, 2H, CH.sub.2), 2.68-2.76 (m, 2H, CH.sub.2), 3.22-3.26 (m, 2H, CH.sub.2), 3.60 (s, 3H, CH.sub.3), 3.80 (s, 3H, CH.sub.3), 5.24 (s, 2H, CH.sub.2), 7.13-7.45 (m, 4H, Ar—H), 7.66 (s, 1H, CH).

(48) Compound 131 .sup.1HNMR (400 MHz, CDCl.sub.3): 2.83 (s, 1H, CH), 3.72 (s, 3H, CH.sub.3), 3.85 (s, 3H, CH.sub.3), 5.13 (d, 2H, CH.sub.2), 5.42 (s, 2H, CH.sub.2), 6.73 (s, 1H, pyrimidyl-H), 7.23 (t, 1H, Ar—H), 7.39 (q, 2H, Ar—H), 7.49 (t, 1H, Ar—H), 7.60 (s, H, CH).

(49) Compound 145 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.31 (s, 3H, CH.sub.3), 3.73 (s, 3H, CH.sub.3), 3.77-3.78 (d, 2H, CH.sub.2), 3.91 (s, 3H, CH.sub.3), 5.09-5.11 (d, 1H), 5.23 (s, 2H, CH.sub.2), 5.27-5.31 (d, 1H), 5.89-5.99 (d, 1H) 6.40 (s, 1H, pyrimidyl-H), 7.23-7.54 (m, 4H, Ar—H).

(50) Compound 146 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.73 (s, 3H, CH.sub.3), 3.81-3.83 (d, 2H, CH.sub.2), 3.91 (s, 3H, CH.sub.3), 5.12-5.14 (d, 1H), 5.33 (s, 2H, CH.sub.2), 5.30-5.35 (m, 1H), 5.90-6.01 (m, 1H), 6.73-7.00 (m, 1H, CHF.sub.2), 6.76 (s, 1H, pyrimidyl-H), 7.25-7.64 (m, 4H, Ar—H).

(51) Compound 147 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.73 (s, 3H, CH.sub.3), 3.82-3.84 (d, 2H, CH.sub.2), 3.92 (s, 3H, CH.sub.3), 5.12-5.14 (d, 1H), 5.36 (s, 2H, CH.sub.2), 5.31-5.36 (m, 1H), 5.90-6.00 (m, 1H), 7.05 (s, 1H, pyrimidyl-H), 7.26-7.66 (m, 4H, Ar—H).

(52) Compound 163 .sup.1HNMR (400 MHz, CDCl.sub.3): 1.77 (s, 6H, 2CH.sub.3), 3.88 (s, 3H, CH.sub.3), 4.05 (s, 3H, CH.sub.3), 3.82 (d, 2H, CH.sub.2), 5.36 (s, 2H, CH.sub.2), 5.38 (t, 1H, CH), 6.65 (s, 1H, pyrimidyl-H), 7.24 (d, 1H, Ar—H), 7.43-7.48 (m, 2H, Ar—H), 7.53 (d, 1H, Ar—H).

(53) Compound 177 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.34 (s, 3H, CH.sub.3), 3.72 (s, 3H, CH.sub.3), 3.91 (s, 3H, CH.sub.3), 4.14 (s2H, CH.sub.2), 5.23 (s, 2H, CH.sub.2), 5.34 (d, 1H), 5.59 (d, 1H), 6.40 (s, 1H, pyrimidyl-H), 7.22-7.57 (m, 4H, Ar—H).

(54) Compound 178 .sup.1HNMR (400 MHz, CDCl.sub.3): 3.88 (s, 3H, CH.sub.3), 4.05 (s, 3H, CH.sub.3), 4.08 (s, 2H, CH.sub.2), 5.34 (d, 1H, CH.sub.2), 5.57 (d, 1H, CH.sub.2), 5.35 (s, 2H, CH.sub.2), 6.65 (s, 1H, pyrimidyl-H), 7.24 (d, 1H, Ar—H), 7.43-7.49 (m, 2H, Ar—H), 7.54 (d, 1H, Ar—H).

(55) Compound 179 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.74 (s, 3H, CH.sub.3), 3.92 (s, 3H, CH.sub.3), 4.20 (s, 2H, CH.sub.2) 5.37 (s, 2H, CH.sub.2), 5.38-5.39 (d, 1H, CH.sub.2), 5.62 (d, 1H, CH.sub.2), 5.59 (d, 1H), 7.09 (s, 1H, pyrimidyl-H) 7.26-7.61 (m, 4H, Ar—H).

(56) Compound 180 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.15-1.19 (m, 3H, CH.sub.3), 2.58-2.64 (m, 2H, CH.sub.2), 3.74 (s, 3H, CH.sub.3), 3.91 (s, 2H, CH.sub.2), 4.15 (s, 2H, CH.sub.2), 5.24 (s, 2H, CH.sub.2), 5.34 (d, 1H), 5.59 (d, 1H), 6.41 (s, 1H, pyrimidyl-H), 7.23-7.55 (m, 4H, Ar—H).

(57) Compound 191 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.94 (s, 3H, CH.sub.3), 2.32 (s, 3H, CH.sub.3), 3.72 (s, 3H, CH.sub.3), 3.91 (s, 3H, CH.sub.3), 4.11 (s2H, CH.sub.2), 5.24 (s, 2H, CH.sub.2), 5.33 (d, 1H), 5.58 (d, 1H), 6.40 (s, 1H, pyrimidyl-H), 7.25-7.58 (m, 4H, Ar—H).

(58) Compound 193 .sup.1HNMR (400 MHz, CDCl.sub.3) 2.37 (s, 3H, CH.sub.3), 3.76 (d, 0.6*2H, CH.sub.2), 3.94 (d, 0.4*2H, CH.sub.2), 3.86 (s, 0.6*3H, CH.sub.3), 3.87 (s, 0.4*3H, CH.sub.3), 4.03 (s, 0.6*3H, CH.sub.3), 4.04 (s, 0.4*3H, CH.sub.3), 5.30 (s, 2H, CH.sub.2), 6.14 (d, 0.4*1H, CH), 6.21 (d, 0.6*1H, CH), 6.28 (s, 0.4*1H, pyrimidyl-H), 6.29 (s, 0.6*1H, pyrimidyl-H), 7.22 (d, 1H, Ar—H), 7.40-7.47 (m, 2H, Ar—H), 7.50 (d, 1H, Ar—H).

(59) Compound 194 .sup.1HNMR (400 MHz, CDCl.sub.3): 3.78 (s, 3H, CH.sub.3), 4.03 (s, 0.3*:3H, CH.sub.3), 4.04 (d, 0.7*2H, CH.sub.2), 3.78 (d, 0.7*2H, CH.sub.2), 3.95 (d, 0.3*2H, CH.sub.2) 6.01-6.07 (m, 1H), 6.18 (d, 0.3*2H, CH.sub.2), 6.26 (d, 0.7*2H, CH.sub.2), 6.41 (t, 1H, CHF.sub.2), 6.65 (s, 1H, pyrimidyl-H), 7.24 (d, 1H, Ar—H), 7.42-7.51 (m, 2H, Ar—H), 7.54 (d, 1H, AR—H)

(60) Compound 195 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.74 (s, 3H, CH.sub.3), 3.94 (s, 3H, CH.sub.3), 3.86-3.95 (m, 2H, CH.sub.2) 5.37 (s, 2H, CH.sub.2), 6.04-6.17 (m, 1H, CH), 6.47-6.54 (m, 1H, CH), 7.07 (s, 1H, pyrimidyl-H), 7.26-7.59 (m, 4H, Ar—H).

(61) Compound 199 .sup.1HNMR (400 MHz, CDCl.sub.3): 0.96-1.11 (m, 4H, cyclopropyl-2CH.sub.2), 1.83-1.87 (m, 1H, cyclopropyl-CH), 3.86 (s, 3H, CH.sub.3), 4.02 (s, 0.5*3H, CH.sub.3), 4.03 (d, 0.5*2H, CH.sub.2), 3.70 (d, 0.5*2H, CH.sub.2), 3.87 (d, 0.5*2H, CH.sub.2), 5.98-6.06 (m, 1H), 6.14 (d, 0.5*2H, CH.sub.2), 6.18 (d, 0.5*2H, CH.sub.2), 6.24 (s, 0.5*1H, pyrimidyl-H), 6.25 (s, 0.5*1H, pyrimidyl-H), 7.21 (t, 1H, Ar—H), 7.38-7.45 (m, 2H, Ar—H), 7.50 (d, 1H, Ar—H).

(62) Compound 209 .sup.1HNMR (400 MHz, CDCl.sub.3): 2.38 (s, 3H, CH.sub.3), 3.85 (d, 2H, CH.sub.2), 3.86 (s, 3H, CH.sub.3), 4.04 (s, 3H, CH.sub.3), 5.30 (s, 2H, CH.sub.2), 6.11 (1H, CH), 7.22 (d, 1H, Ar—H), 7.40-7.46 (m, 2H, Ar—H), 7.51 (t, 1H, Ar—H)

(63) Compound 210 .sup.1HNMR (400 MHz, CDCl.sub.3) 3.88 (s, 3H, CH.sub.3), 4.04 (s, 3H, CH.sub.3), 3.88 (d, 2H, CH.sub.2), 5.35 (s, 2H, CH.sub.2), 6.10 (t, 1H, CH), 6.66 (s, 1H, pyrimidyl-H), 7.24 (d, 1H, Ar—H), 7.43-7.7.48 (m, 2H, Ar—H), 7.50 (d, 1H, Ar—H)

(64) Compound 211 .sup.1HNMR (400 MHz, CDCl.sub.3): 3.88 (s, 3H, CH.sub.3), 4.05 (s, 3H, CH.sub.3), 3.89 (d, 2H, CH.sub.2), 5.37 (s, 2H, CH.sub.2), 6.70 (s, 1H, pyrimidyl-H), 7.25 (d, 1H, Ar—H), 7.44-7.49 (m, 2H, Ar—H), 7.53 (d, 1H, Ar—H)

(65) Compound 212 .sup.1HNMR (400 MHz, CDCl.sub.3): 1.26 (3H, CH.sub.3), 2.66 (q, 2H, CH.sub.2), 3.85 (d, 2H, CH.sub.2), 3.86 (s, 3H, CH.sub.3), 4.03 (s, 3H, CH.sub.3), 5.30 (s, 2H, CH.sub.2), 6.11 (1, 1H, CH), 6.25 (s, 1H, pyrimidyl-H), 7.22 (d, 1H, Ar—H), 7.40-7.46 (m, 2H, Ar—H), 7.51 (1, 1H, Ar—H).

(66) Compound 213 .sup.1HNMR (400 MHz, CDCl.sub.3): 0.98 (t, 3H, CH.sub.3), 1.69-11.76 (m, 2H, CH.sub.2), 2.60 (t 2H, CH.sub.2), 3.86 (d, 2H, CH.sub.2), 3.87 (s, 3H, CH.sub.3), 4.04 (s, 3H, CH.sub.3), 5.30 (s, 2H, CH.sub.2), 6.11 (t, 1H, CH), 6.24 (s, 1H, pyrimidyl-H), 7.23 (d, 1H, Ar—H), 7.43-7.47 (m, 2H, Ar—H), 7.51 (d, 1H, Ar—H)

(67) Compound 215 .sup.1HNMR (400 MHz, CDCl.sub.3): 1.00-1.12 (m, 4H, cyclopropyl-2CH.sub.2), 1.84-1.87 (m, 1H, cyclopropyl-CH), 3.87 (s, 3H, CH.sub.3), 3.79 (d, 2H, CH.sub.2), 4.04 (s, 3H, CH.sub.3), 5.30 (s, 2H, CH.sub.2), 6.08 (1, 1H, CH), 6.27 (s, 1H, pyrimidyl-H), 7.22 (d, 1H, Ar—H), 7.40-7.46 (m, 2H, Ar—H), 7.50 (d, H, Ar—H).

(68) Compound 257 .sup.1HNMR (400 MHz, CDCl.sub.3): 2.70-2.82 (m, 2H, CH.sub.2), 3.28 (1, 2H, CH.sub.2), 3.86 (s, 3H, CH.sub.3), 4.02 (s, 3H, CH.sub.3), 5.29 (s, 2H, CH.sub.2), 6.24 (s, 1H, pyrimidyl-H), 7.23 (d, 1H, Ar—H), 7.41-7.47 (m, 2H, Ar—H), 7.50 (d, H, Ar—H).

(69) Compound 258 .sup.1HNMR (400 MHz, CDCl.sub.3): 2.73-2.80 (m, 2H, CH.sub.2), 3.31 (1, 2H, CH.sub.2), 3.88 (s, 3H, CH.sub.3), 4.04 (s, 3H, CH.sub.3), 5.35 (s, 2H, CH.sub.2), 6.40 (t, 1H, CHF.sub.2), 6.65 (s, 1H-pyrimidyl-H), 7.25 (d, 1H, Ar—H), 7.43-7.48 (m, 2H, Ar—H), 7.53 (d, H, Ar—H).

(70) Compound 259 .sup.1HNMR (400 MHz, CDCl.sub.3): 2.74-2.83 (m, 2H, CH.sub.2), 3.33 (t, 2H, CH.sub.2), 3.88 (s, 3H, CH.sub.3), 4.04 (s, 3H, CH.sub.3), 5.36 (s, 2H, CH.sub.2), 6.69 (s, 1H, pyrimidyl-H), 7.25 (d, 1H, Ar—H), 7.44-7.49 (m, 2H, Ar—H), 7.53 (d, H, Ar—H).

(71) Compound 260 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.15-1.19 (m, 3H, CH.sub.3), 2.57-2.63 (m, 2H, CH.sub.2), 2.73-2.82 (m, 2H, CH.sub.2), 3.27-3.30 (m, 2H, CH.sub.2), 3.73 (s, 3H, CH.sub.3), 3.90 (s, 3H, CH.sub.3), 5.23 (s, 2H, CH.sub.2), 6.40 (s, 1H, pyrimidyl-H), 7.23-7.54 (m, 4H, Ar—H).

(72) Compound 261 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.86-0.90 (m, 3H, CH.sub.3), 1.62-1.67 (m, 2H, CH.sub.2), 2.51-2.57 (m, 2H, CH.sub.2), 2.74-2.80 (m, 2H, CH.sub.2), 3.25-3.28 (m, 2H, CH.sub.2), 3.72 (s, 3H, CH.sub.3), 3.89 (s, 3H, CH.sub.3), 5.22 (s, 2H, CH.sub.2), 6.40 (s, 1H, pyrimidyl-H), 7.24-7.54 (m, 4H, Ar—H)

(73) Compound 262 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.17-1.19 (d, 6H, CH.sub.3), 2.75-2.89 (m, 3H, CH, CH.sub.2), 3.26-3.29 (m, 2H, CH.sub.2), 3.78 (s, 3H, CH.sub.3), 3.90 (s, 3H, CH.sub.3), 5.22 (s, 2H, CH.sub.2), 6.40 (s, 1H, pyrimidyl-H), 7.24-7.55 (m, 4H, Ar—H)

(74) Compound 263 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.98-1.00 (m, 4H, cyclopropyl-2CH.sub.2), 1.98-2.05 (m, H, CH), 2.69-2.79 (m, 2H, CH.sub.2), 3.21-3.24 (in, 2H, CH.sub.2), 3.74 (s, 3H, CH.sub.3), 3.90 (s, 3H, CH.sub.3), 5.20 (s, 2H, CH.sub.2), 6.48 (s, 4H, Ar—H).

(75) Compound 271 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.07 (s, 3H, CH.sub.3), 2.34 (s, 3H, CH.sub.3), 2.71-2.79 (m, 2H, CH.sub.2), 3.23-3.26 (m, 2H, CH.sub.2), 3.71 (s, 3H, CH.sub.3), 3.90 (s, 3H, CH.sub.3), 5.24 (s, 2H, CH.sub.2), 7.24-7.54 (m, 4H, Ar—H).

(76) Compound 272 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.84-0.87 (m, 3H, CH.sub.3), 1.25-1.38 (m, 2H, 2CH.sub.2), 2.34 (s, 3H, CH.sub.3), 2.42-2.46 (m, 2H, CH.sub.2), 2.69-2.79 (m, 2H, CH.sub.2), 3.23-3.27 (m, 2H, CH.sub.2), 3.72 (s, 3H, CH.sub.3), 3.91 (s, 3H, CH.sub.3), 5.24 (s, 2H, CH.sub.2), 7.25-7.54 (m, 4H, Ar—H).

(77) Compound 238 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.75 (s, 3H, CH.sub.3), 3.92 (s, 3H, CH.sub.3), 3.84-3.94 (m, 2H, CH.sub.2), 5.50 (s, 2H, CH.sub.2), 6.06-6.15 (m, 1H, CH), 6.44-6.54 (m, 1H, CH), 6.87-7.03 (m, 1H, CHF.sub.2), 6.94 (s, 1H, pyrimidyl-H), 7.45-7.59 (m, 4H, Ar—H).

(78) Compound 353 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 2.34 (s, 3H, CH.sub.3), 3.66 (s, 3H, CH.sub.3), 3.68 (s, 3H, C.sub.3), 3.83-3.85 (d, 2H, CH.sub.2), 5.41 (s, 2H, CH.sub.2), 6.23-6.26 (m, 1H, CH), 6.59 (s 1H, pyrimidyl-H), 7.40-7.46 (m, 4H, Ar—H).

(79) Compound 354 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 3.66 (s, 3H, CH.sub.3), 3.68 (s, 3H, CH.sub.3), 3.89-3.91 (d, 2H, CH.sub.2), 5.50 (s, 2H, CH.sub.2), 6.28-6.32 (m, 1H, CH), 6.74-7.01 (m, 1H, CHF.sub.2) 6.96 (s, 1H, pyrimidyl-H), 7.41-7.58 (m, 4H, Ar—H).

(80) Compound 404 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.16-1.20 (m, 3H, CH.sub.3) 2.59-2.63 (m, 2H, CH.sub.2), 2.72-2.82 (m, 2H, CH.sub.2), 3.27-3.31 (m, 2H, CH.sub.2), 3.67 (s, 3H, CH.sub.3), 3.69 (s, 3H, CH.sub.3), 5.41 (s, 2H, CH.sub.2), 6.55 (s, 1H, pyrimidyl-H), 7.42-7.56 (m, 4H, Ar—H).

(81) Compound 405 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.87-0.91 (m, 3H, CH.sub.3), 1.62-1.69 (m, 2H, CH.sub.2), 2.55-2.59 (m, 2H, CH.sub.2), 2.73-2.82 (m, 2H, CH.sub.2), 3.27-3.31 (m, 2H, CH.sub.2), 3.66 (s, 3H, CH.sub.3), 3.69 (s, 3H, CH.sub.3), 5.41 (s, 2H, CH.sub.2), 6.54 (s, 1H, pyrimidyl-H) 7.41-7.59 (m, 4H, Ar—H).

(82) Compound 406 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 1.18-1.20 (d, 6H, 2CH.sub.3) 1.98-2.01 (m, H, CH), 2.75-2.90 (m, 2H, CH.sub.2), 3.28-3.32 (m, 2H, CH.sub.2), 3.66 (s, 3H, CH.sub.3), 3.69 (s, 3H, CH.sub.3), 5.40 (s, 2H, CH.sub.2), 6.54 (s, 1H, pyrimidyl-H), 7.40-7.59 (m, 4H, Ar—H).

(83) Compound 407 .sup.1HNMR (400 MHz, DMSO) δ (ppm): 0.99-1.02 (m, 4H, cyclopropyl-2CH.sub.2), 1.98-2.01 (m, H, CH), 1.98-2.01 (m, H, CH), 2.75-2.90 (m, 2H, CH.sub.2), 3.20-3.35 (m, 2H, CH.sub.2), 3.66 (s, 3H, CH.sub.3), 3.69 (s, 3H, CH.sub.3), 5.34 (s, 2H, CH.sub.2), 6.53 (s, 1H, pyrimidyl-H), 7.41-7.59 (m, 4H, Ar—H).

PREPARATION EXAMPLES

(84) The addition amount of each component is a weight percentage. The active ingredient in formulation can be selected from any of the compounds of formula (I) of the present invention and the addition amount of which is calculated by multiplying weight by purity.

Example 5

30% Wettable Powder

(85) TABLE-US-00005 Compound 81    30% Sodium dodecyl sulfate     2% Sodium lignostilionate     3% Naphthalenesulfonic acid formaldehyde condensate     5% Light calcium carbonate up to 100%

(86) The compound and other components were fully mixed, and crushed by an ultrafine pulverizer to obtain 30% wettable powder product.

Example 6

40% Suspension Concentrate

(87) TABLE-US-00006 Compound 81     40% Ethylene glycol     10% Nonylphenol polyglycol ether      6% Sodium lignosulfonate     10% Carboxymethyl cellulose     1% 37% formaldehyde solution    0.2% 75% silicone oil emulsion    0.8% Water up to 100%

(88) The compound and other components were fully mixed to obtain the suspension concentrate, which can be diluted with water to obtain a diluent at any required concentration.

Example 7

60% Water-Dispersible Granules

(89) TABLE-US-00007 Compound 81    60% Sodium naphthalene sulfonate formaldehyde condensate    12% N-methyl-N-oleoyl-taurate sodium     8% Polyvinylpyrrolidone     2% Carboxymethyl cellulose     2% Kaolin up to 100%

(90) The compound and other components were mixed and pulverized, then kneaded with water, granulated in a granulator with a 10-100 mesh sieve, then dried and sieved according to sieve range to obtain 60% water-dispersible granules.

(1) Testing Examples of Biological Activity

(91) Activity test experiments of the compound of the present invention against adults of Tetranychus cinnabarinus were carried out. The test methods are as follow:

Example 8

Insecticidal Activity Test

(92) A certain amount of the original drug was weighed by an analytical balance (0.0001 g), and dissolved in DMF containing 1% Tween-80 emulsifier to prepare a 1% mother liquor, which was then diluted with distilled water for later use.

(93) The insecticidal efficacy was evaluated by a leaf-dipping method with the armyworm as a target and a spray method with Tetranychus cinnabarinus and Aphis craccivora Koch as a target.

(94) Activity Test of Armyworm

(95) Leaf-dipping method: the target for the test was the armyworm, and corn leaves in an appropriate amount were fully infiltrated in the prepared liquid, then dried naturally, placed in culture dishes with filter papers, inoculated with 3rd instar larvae of the armyworm at 10 heads/dish, and placed in an observation room and cultured at 24˜27° C. the results were investigated after 3 days. A brush was used to touch the insect bodies, and the unresponsive were regarded as dead insects.

(96) Partial Test Results are as Follow:

(97) At a test concentration of 500 mg/L, compounds 1, 49, 50, 55, 65, 68, 71, 114, 115, 131, 163, 191, 195, 209, 210, 212, 262, 263, 272, 339, 358, 404, 407 had a lethal rate of more than 80% on aphids;

(98) Compounds 9, 34, 35, 36, 51, 67, 113, 116, 118, 117, 119, 128, 145, 147, 178, 179, 180, 193, 194, 199, 211, 213, 214, 215, 260 261, 271, 337, 338, 353,354, 356, 357, 359, 405, 406, 549 had a lethal rate of 100% on aphids;

(99) Compounds 68, etc at 100 mg/L had a lethal rate of more than 80% on aphids.

Example 9

Activity Test of Tetranychus Cinnabarinus and Aphis Craccivora Koch

(100) Spray method: the target for the test was Tetranychus cinnabarinus and Aphis craccivora Koch, that is, broad bean leaves inoculated with Tetranychus cinnabarinus and Aphis craccivora Koch, respectively, were placed under the spray treatment of Potter spray tower. After the treatment, the Tetranychus cinnabarinus were placed in an observation room and cultured at 24˜27° C., the Aphis craccivora Koch was placed in an observation room and cultured at 20˜22° C., and the results were investigated after 2 days. A brush was used to touch the insect body, and the unresponsive were regarded as dead insects.

{circumflex over (1)} Activity Assay of Tetranychus Cinnabarinus

(101) At the test concentration of 500 mg/L, the lethal rate of compounds 19, 34, 49, 55, 114, 128, 179, 261, 263, 339 on. Tetranychus cinnabarinus was more than 80%; the lethal rate of compounds 9, 10, 35, 51, 67, 113, 116, 117, 118, 119, 260, 262, 50, 1, 55, 127, 147, etc. on Tetranychus cinnabarinus was more than 100%.

(102) At the concentration of 100 mg/L, the lethal rite of compounds 10, 1, 49, 55, 113, 119, 147, 179, etc. on Tetranychus cinnabarinus was more than 50%; the lethal rate of compounds 116, 117, 118, 35, 67, 50, 9, 127, 128, 51, 34, 19, etc. on Tetranychus cinnabarinus was more than 80%.

(103) At the concentration of 20 mg/l the lethal rate of compounds 1, 34, 35, etc. on Tetranychus cinnabarinus was more than 50%; the lethal rate of compounds 9, 19, 51, 67, 128, etc. on Tetranychus cinnabarinus was more than 80%.

{circumflex over (2)} Activity Assay of Aphis Craccivora Koch

(104) At the test concentration of 500 mg/L, the lethal rate of compounds 113, 116, 119 on Aphis craccivora Koch was more than 80%.

(2) Test Example of Living Protection Activity

Example 10

Prevention Experiment of Powdery Mildew of Cucumber

(105) Experimental Method was as Follows:

(106) The living pot assay method was adopted, that is, the sample of the test compound was dissolved with a small amount of DMF solvent (the kind of solvent such as acetone, methanol, DMF, etc., is selected according to the solvency of the sample, and the volume ratio of the solvent amount to the spray amount is equal to or less than 0.05), diluted with water containing 0.1% Tween 80, and formulated into the test solution with a desired concentration. Cucumber seedlings at leaf period with the same growth period was sprayed evenly with the prepared agent, and aired. Each concentration was one treatment, each treatment was repeated 3 times, a control agent and a water of blank control were set separately. The fresh powdery mildew spores on the leaves of cucumbers were washed and filtered with double gauze to prepare a suspension with a concentration of about 100,000 spores/mL. The samples were inoculated by spraying, the inoculated samples were moved into artificial climate, and relative humidity was maintained at 60-70%, the temperature was maintained at 23° C., after about 10 days, grading investigation was carried out according to the morbidity of the blank control, control effect was calculated according to disease index.

(107) Test results of living protection activity of partial compounds were as follows:

(108) At a concentration of 200 ppm, compounds 10, 19, 128, 147, 163, 195, 210, 211, 212, 257, 258, 259, 401, 402, etc. had an effect of preventing powdery mildew by more than 80%; compounds 1, 9, 34, 35, 36, 49, 50, 51, 55, 67, 113, 114, 127, 128, 146, 177, 178, 179, 180, 191, 193, 194, 199, 271, etc. had an effect of preventing powdery mildew by 100%.

(109) At a concentration of 100 ppm, compounds 1, 51, 36, 55, 113, 114, 258, 218, 194, 146, 147, 177, 178, 191 had an effect of preventing powdery mildew by more than 50%; compounds 9, 35, 49 50, 127, 195, 212, 271, etc. had an effect of preventing powdery mildew effect by more than 80%;

(110) At a concentration of 50 ppm, compounds 9, 50, 127, etc. had an effect of preventing powdery mildew by more than 80%.

(3) Testing Example of Acaricidal Activity of Partial Compounds and Control Compounds

(111) Experimental Methods were as Follows:

(112) Spray method: the test target was Tetranychus cinnabarinus, that is, broad bean leaves inoculated with adults of Tetranychus cinnabarinus were placed under the spray treatment of Potter spray towers. After treatment, the Tetranychus cinnabarinus was placed in an observation room and cultured at 25˜27° C., and the results were investigated after 48 hours. The brush was used to touch the insect body, and the unresponsive were regarded as dead insects. The test concentrations of the compounds on killing cinnabarin were 50, 25, 12.5, 6.25, 3.125 mg/L.

(113) Egg test: each treated broad bean leave was inoculated with 10 adults of Tetranychus cinnabarinus, and the adults were removed after the eggs were laid for 24 hours. The leaves with eggs were sprayed under Potter spray towers. After treatment, the eggs of Tetranychus cinnabarinus were placed in an observation room and cultured at 25˜27° C. And the test was examined until the eggs under the blank treatment completely hatched out. The concentration of the compound that kills the eggs of Tetranychus cinnabarinus was 100, 50, 25, 12.5, 6.25 mg/L.

(114) Nymph test: broad bean leaves were inoculated with 10 adult mites, and the adults were removed after laying eggs for 24 hours. The eggs were fed in insect rearing room, and when they hatched into nymphs, they were sprayed with a sprayer. After treatment, the leaves with the nymphs were placed in an observation room and cultured at 25-27° C., and the results were investigated after 48 hours. A brush was used to touch the insect bodies, and the unresponsive were regarded as the dead. The test concentrations of the compound on killing cinnabarin were 5, 2.5, 1.25, 0.625, 0.3125 mg/L.

(115) The comparison test results were as follows:

(116) In the cases where compound 67 and fluacrypyrim were given at a concentration of 50, 25, and 12.5 mg/L, respectively, the lethal rate of compound 67 against adult mites was better than that of fluacrypyrim.

(117) In the cases where compound 67 and fluacrypyrim were given at a concentration of 100, 50, 25, 12.5, 6.25 mg/L, respectively, the lethal rate of compound 67 on eggs of Tetranychus cinnabarinus was better than that of fluacrypyrim.

(118) In the cases where compound 67 and fluacrypyrim were given at a concentration of 5, 2.5, 1.25, 0.625, 0.3125 mg/L, respectively, the lethal rate of compound 67 on nymphs of Tetranychus cinnabarinus was better than that of fluacrypyrim.

(119) TABLE-US-00008 TABLE 5 toxicity test data of compound 67 and fluacrypyrim on adults of Tetranychus cinnabarinus Concentration Mortality Agent (mg/L) (%) 67 50 92.41 25 81.06 12.5 70.83 6.25 61.94 3.125 30.19 Fluacrypyrim 50 88.89 25 75.94 12.5 70.59 6.25 64.58 3.125 39.55 CK — 7.69

(120) TABLE-US-00009 TABLE 6 toxicity test data of compound 67 and fluacrypyrim on eggs of Tetranychus cinnabarinus Concentration Mortality Agent (mg/L) (%) 67 100 93.14 50 81.10 25 65.61 12.5 33.14 6.25 15.13 Fluactypyrim 100 75.00 50 54.86 25 32.16 12.5 13.59 6.25 10.84 CK — 12.02

(121) TABLE-US-00010 TABLE 7 toxicity test data of compound 67 and fluacrypyrim on nymphs of Tetranychus cinnabarinus Concentration Mortality Agent (mg/L) (%) 67 5 90.32 2.5 73.08 1.25 53.99 0.625 26.22 0.3125 15.00 Fluacrypyrim 5 82.48 2.5 55.29 1.25 28.76 0.625 17.14 0.3125 7.74 CK — 4.76