TWI306016B - Cyclic amine compound and pest control agent - Google Patents

Description

[Technical Field] The present invention relates to a novel cyclic amine compound and a pest control agent containing the cyclic amine as an active ingredient. [Prior Art] Since then, many insecticides and acaricides have been used, but the fruit is not good enough. Because of the drug tolerance, the use is limited, and the phytotoxicity or production of the plant Pollution, or the presence of strong 'sex' in humans, animals, etc., are not satisfactory inhibitors. I hope that I can develop drugs that have fewer defects and are safe to use. A compound having a skeleton similar to the compound of the present invention is, for example, an antiviral agent disclosed in the specification of European Patent Application Publication No. 0 605 031. However, it has not been carried out, and it has an insecticidal activity, (iv) activity, and for the present hairpin. Synthesis and biological activity of the compound So far, i has no relevant report. 0 L invention content] The purpose of human formation is to provide a novel compound, which is advantageous for the industrialization of α 2 as a practical and safe pest control agent. That is, X, the present invention is a formula [I] 1306016 oxy group or the like. The methylthio group, the ethylthio group, the propyl sulfide C!-6 alkylthio group has, for example, a group. The c i -6 halogen group thio group may, for example, be a group, a trifluoromethylthio group or the like. The C 1 · 6 alkyl sulfite group has, for example, an anthracenyl group, a propyl sulfinyl group or the like. Monofluoromethylthio, difluoromethylsulfide, ‘methylsulfinyl, ethyl sulfite, C 1  6 ώ 基 亚 亚 你

For example, there are 'trifluoromethylmethylsulfinylene group, pentafluoroethyl sulfinylene group and the like.

Examples of the Cl.6-based sulfhydryl group include a methyl gal group, a benzyl group, and the like. For example, C, 6 alkylsulfonyloxy has, for example, methylsulfonyloxy or ethanesulfonate. An alkoxy group, etc. C]. 6 dentate thiol oxo group, for example, a tri-I methyl decyloxy group, a pentafluoroethyl sulfonyloxy group, etc. 丨-6 alkoxy alkoxy group, for example,曱 methoxymethoxy, methoxyethoxy, ethoxymethoxy, etc. C3-6 cycloalkyl, for example, cyclopropyl, 1-methylcyclopropyl, 2,2,3,3-tetra Base propyl, cyclobutyl, cyclopentyl,]-fluorenylcyclopentyl, cyclohexyl, 1-methylcyclohexyl, 4-methylcyclohexyl, etc. C6-i. For example, aryl a naphthyl group or the like. A 5-membered ring containing at least one selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom, and a 6-membered ring heterocyclic group, for example, tetrahydroanthracene*, dioxalanyl group 1306016, thiophene group , 1,2,3-oxadiazolyl, oxazolyl, iota, 3-dioxolanyl group, 4,5-dihydroindenyl, furyl, etc. Hungry 〇 or 1~5 The integer, if there are multiple Ri, can be the same or different. The integer represented by k, if there are multiple feet 2, The same or different.

R3 and R4, or R^R6 of the formula (1) may form a saturated ring. When R3 /, R, or R forms a saturated ring together with R6', as a whole, a ring of bismuth [3.2·1] octyl ring (hereinafter referred to as a tortoise ring), 3_ 丫 丫Ring [3_2.1] cross-linked ring of octyl ring (1 Γ, called iotatropin), 3·α丫 bicyclo[m] decane. Further, there is a compound having a nitrogen atom of the compound of the present invention m or a nitrogen atom oxidized by a cyclic amine such as a bituminous, a torazine ring or an isotropine ring, and the N-oxides are included in Within the invention. Together with R4' or R5 and R6 form a saturated isomer. When the isomers include R3 and a ring of the compound [I] of the present invention, each of the following is exemplified in the present invention. 11 1306016

The method for producing the compound of the present invention will be described below. First, a method of manufacturing the intermediate body (3) will be described. 12 1306016

[In the formula, 'R1~^^, ^, ^, ^, ^, and ^(1) have the same meaning, Xl and X2 are independent, representing a hydroxyl group or a thiol group, X3 is a leaving group of a 素 atom, and X4 is represented by An oxygen atom or a sulfur atom. Further, R represents either a 2-pyridyl group, a methyl group or a benzyl group substituted by R2k. The intermediate (3) can be subjected to a dehydration reaction in the form of the compound (1) and the chemical compound (2), for example, a Mitsunbubu reacti〇n, as shown in the reaction formula (III). For example, Tetrahedr〇n Lett, 1978, 2243 or 】

Manufactured by the method described in Chem., 50, 3095, 1985, etc.). The compound (1) can be used by a known method (for example, "The Chemistry 〇f Phenols.,, Eds. z

RapP〇port, j. Wiley (2〇〇3) partl, pp395, etc.), and, as shown in the reaction formula (IV), can be coupled by an aryl halide (4) and a compound (2). Manufacturing intermediates. Specifically, a well-known method can be used (for example, Synth. Commun., 1984, 14, 621; J. Org Chem., 48, 1313006016, 1000 (1974), etc., 3771 (1993). Or, manufactured by J. Med. Chem, France). ... At this time, the test can be used, such as sodium hydroxide, hydroxide, etc., metal hydroxide, sodium carbonate, potassium carbonate and other carbonates, sodium methoxide, potassium butoxide, magnesium oxide, etc. An organic metal such as n-butyllithium or LDA, a metal hydride such as sodium hydride or potassium hydride, or an organic base such as triethylamine, diisopropylamine or pyridin. This reaction can be carried out in the presence or absence of a solvent. The solvent which can be used is not particularly limited as long as it is inactive to the reaction, and may be, for example, a hydrocarbon solvent such as pentane, hexane, heptane, benzene, toluene or xylene, dioxane or hydrazine. , 2_dichloroethane, chloroform, halogenated solvent such as carbon tetrachloride, nitrile solvent such as acetonitrile or propionitrile, ether solvent such as diethyl ether, hydrazine, analoxane ring, tetrahydrofuran, N, N_ An aprotic polar solvent such as methylformamide (DMF) or sulfamethoxazole (DMSO), or a mixed solvent of two or more of these solvents. The reaction temperature may be any temperature within the temperature range of _78ac~ the solvent used. In the compound (2), when the R is a 2-pyridine group substituted with R2 (compound (7))', the compound [I] of the present invention can be directly produced by the reaction formula (III) or the reaction formula (1). As shown in the reaction formula (V), the compound (7) can be synthesized by coupling the amine (5) with 2-halo. Specifically, it can be produced by a known method (for example, Synthesis, 1981, 606; J. Chem. Soc" C, 3693 (1971), etc.) 1306016

Alkali

(7) R61, η, X2 and χ3 with

[In the formula, the same is true (6) R2~R7, R31, R4i, R5i

In the other aspect, in the compound (2), when the ruler is a methyl group or a fluorenyl group, it is necessary to demethylate or de-follow the intermediate (3) obtained by the reaction formula (ΙΠ) or the reaction formula (IV). . Demethylation can be performed using well-known methods (for example, Tetrahedr〇n

Leu" 1974, 1325; ibid" 1977, 1565; ibid., 1995, 8867, etc.). The debenzylation can be carried out by using a known contact hydrogen reduction or the like. The compound of the present invention [Γ] can be produced by coupling the intermediate (8) from the intermediate (3) and coupling with the tooth pyridine (6) as shown in the reaction formula (VI). The specific method of coupling is the same as the reaction formula (V).

(VI) 15 r? 1306016 Valley thieves, cotton boll weevil, etc. Diptera pests such as, housefly, big black fly, flies, melon flies, oriental fruit flies, fly, rice leaf migratory fly, yellow fruit fly, scorpion fly, three spotted mosquitoes, Egyptian Ivy, Chinese Mosquitoes and so on. For example, there are South Yellow Horses and Small Yellow Horses. Hymenoptera pests are, for example, home worms, yellow wasps, leaf bees, and the like. For example, the Orthoptera pests include the East Asian locust, the German cockroach, the American cockroach, and the black cockroach. Termites such as termites, yellow-breasted termites, etc. For example, there are human mites, mongooses, and the like, and the scorpion pests include, for example, body lice. The mites include, for example, two-spotted spider mites, two-spotted spider mites, espresso leaf mites, citrus leaf mites, apple leaf mites, citrus rust, leaf mites, pseudo-leaf genus, genus eucalyptus, and Robin Root 4, 4 food mites, American dust mites, A island 螨, long-horned blood sputum. Plant parasitic nematodes such as sweet potato root knot nematodes, short-body nematodes, large and golden nematodes, rice stem-tailed nematodes, pine wood nematodes and the like. The preferred pests to be applied are lepidopteran pests, hemipteran pests, mites, tarragon pests, and pteridoptera pests, especially butterflies. In recent years, many pests such as Plutella xylostella, rice worm, spider mites, and alfalfa have produced anti-drugs in organic scales, ammine-based bases or killing agents, resulting in insufficient efficacy of '= hope to have resistance A medicinal pest or an effective agent. The present invention is effective not only for the drug-resistant ancient scorpion, but also for the insects which are resistant to m, guanidin, pyrethroid, and sputum, or to 17 1306016. The anti-drug is a good insecticide and acaricide. The main & the compound of the present invention has a low phytotoxicity and is low in materility to fish or warm-blooded animals. The compound of the present invention can be used as an antifouling agent to prevent water building organisms from adhering to contact with water in the bottom of a ship or a fish net. σ Among the compounds of the present invention, some have bactericidal activity, herbicidal activity, and plant growth δ.中间体 'The intermediate compound of the compound of the present invention has insecticidal and acaricidal action.

The insecticidal or acaricidal agent of the present invention contains the ruthenium or two or more of the compounds of the present invention as an active ingredient. When the compound of the present invention is used in practice, it may be used without adding other components, but usually it is mixed with a solid carrier, a liquid carrier, a gas carrier, or immersed in a base such as a porous ceramic plate or a non-woven fabric, and if necessary, Adding surfactants and other adjuvants to prepare the general form of pesticides, ie 'hydrating agents, granules, powders, emulsions, water-soluble hydrazines, suspending agents, granule hydrating agents, aqueous suspensions, aerosols, aerosols, heating Use in the form of evapotranspiration, fumigant, poison bait, microcapsules, etc. For the preparation of the solidifying agent, vegetable powder such as soybean powder or wheat flour, mineral powder such as diatomaceous earth, apatite, gypsum, talc, bentonite, hydroxyapatite or clay, and benzene may be used as the additive and the support. Organic and inorganic compounds such as formic acid soda, urea, and thenardite. When preparing to be a liquid dosage form, the solvent may be a petroleum fractionation component such as kerosene, diphenylbenzene or solvent oil, cyclohexane, cyclohexanone, dimethylformamide, dimethyl sulfoxide, alcohol, acetone, methyl. Isobutyl ketone, mineral oil, vegetable oil, water, etc. The gaseous carrier which can be used for the spray is a diced gas, LPG, a dimethyl bond, a carbon dioxide gas or the like. 1306016

钭rrontroi), can be made into a key agent, capsule, soaking solution, mixed feed: suppository, injection (intramuscular, subcutaneous, intravenous, intraperitoneal), etc., when re-injection = non-systemic inhibition (__systemiceontrc) 1)1 The raw or aqueous liquid is sprayed, poured (pour.on), dropped (spoton), etc., and the resin preparation is formed into a shape such as a collar or an ear piece to be worn. In this case, it is usually effective to use the compound of the present invention when the compound of the present invention is used alone, but it can also be used with the potted animal, 丨t hangs against the lord animal lkg, using the compound of the present invention 0·01 ～1 〇〇〇mg 〇 Hazardous substance control agents, fungicides, insecticides and acaricides, herbicides, plant conditioners, co-effect agents, fertilizers, soil conditioners, animal feeds, etc., or two or more types of mixed or used together. The active ingredient of a bactericide, an insecticide, an acaricide, a plant growth regulator or the like which may be used in combination with or in combination with the compound of the present invention is represented by the following. Fungicides: Captan, Sterilized Dan, Qiu Laim, Fumei, Daisen Zinc, Mancozeb, Mancozeb, pr〇pinebu, Polyurethane, Gas Talonin, pentacene nitrobenzene (qUint〇zene), captafol, ipr〇dine, saffron diketone, vinclozolin, fluoroquinone, race Mother qi 〇 你 你 (cym〇xani丨), mepronil, flutolanil, pencycur〇n, guava, fosetyl-aluminium, propamocarb ), tridimehon, triadimenol, propiconazol, diclobutrazol, bitertanol, hexaconazole, mccorlo 20 1306016 (microbutanil), flusilaz〇le, etaconazole, fluotrimazole, flutiafen, penc〇naz〇ie吉, you can be (diniconazole), Cypress (Cypr〇c〇liaz〇ie), fenarimol, 赛福座Triflumizole), prochloraz, imazalil, pefurazoate, tridemorph, fenpropimorph 'Trefoil Bean, Bucciobe (buthiobate), Pyrifenox, carbendazim 'polyoxygen _ 素, metalazyl, oxadiXyi, furalaxyl, isoprothiolane , probenazole, pyrrolnitrin, rice saponin s, kasugamycin, validamycin, dihydrostreptomycin sulfate, benomyl, befenfen ( Carbendazim), thiophanate-methyl, hymexazol, alkaline copper chloride, basic copper sulphate, fentin acetate, triphenyltin hydroxide, carbendazim (diethofencarb), methasulfocarb, chinomethionat, binapacryl, lecithin, sodium sulphate, dithianon, dinocap, distillate sodium Fenaminosulf), diclomezine, guazatine, and donin Dine), IBP, edifenphos, mepanipyrim, ferimzone, trichlamide, methasulfocarb, fluazinam , ethoqinolac, dimethomorph, pyroquilon, tecloftalam, fthalide, phenotype 21 1306016 dimethyl ( dimethylvinphos), plus pine (propaphos), ifensone isofenphos, disulfoton, profenofos, pyraclofos, monocrotophos, azinphos-methyl, aldicarb , methodomyl, thiodicarb, carbofuran, carbosulfan, benfuracarb, furathiocarb, propoxur ), BPMC, MTMC, MIPC, carbaryl, pirimicarb, ethiofencarb, fenoxycarb, cartap, thiocyclam, exempt Speed up (bensultap) and so on. Pyrethrin-based insecticides: permethrin, cypermethrin, deltamethrin, fenvalerate, fenpropathrin, pyrethrin ), allethrin, tetramethrin, resumethrin, dimethrin, propathrin, phenothrin, prothrin ), fluvalinate, cyfluthrin, cyhalothrin, flucythrinate, ethofenprox, cycloprothrin, typhine Tralomethrin), silafluofen, acrinathrin, etc. Benzoyl urea is another insecticide: difubenzuron, chlorfluazuron, hexaflumuron, triflumuron, tetraphenyluron 23 1306016, and It was dried over anhydrous magnesium sulfate. The solvent was reduced in a reduced pressure to give Compound (10) (5.98 g). Under ice cooling, a solution of compound (10) (4.9 g), 5-hydroxy-2-nitrobenzotrifluoride (3-2 g) and triphenylphosphine (5.6 g) in THF (30 ml) was added dropwise azo A solution of diisopropyl dicarboxylate (4.3 g) in THF (30 mL). The mixture was warmed to room temperature and stirred for 3 hours, then concentrated under reduced pressure. The residue was purified by column chromatography to yield compound (y. Viscous oil • 'HNMRCCDCB) δ 1.86-1.97 (m, 2H), 2. 〇4- 2.14 (m, 2H), 3.64-3.72 (m, 2H), 3.90-3.99 (m, 2H) 54.71-4.77 ( m,lH), 6.70(d,lH),7.13(d,lH),7.32(d,lH), 7.65(d,lH),8.02(d,lH),8.41(s,lH) Manufacturing Example 2 4 Manufacture of [4-amino-3-(3-trifluoromethyl)phenoxy]-l-[5-(trifluoromethyl)-2-pyridinyl]-octane (Compound No. 1-168) )

Zinc powder (18.8 g) and calcium carbonate dihydrate (1.9 g) were added to a solution of the pyridine (Compound No. 1-39, 5.7 g) obtained in Preparation Example 1 in ethanol (300 ml), and the mixture was heated to reflux. late. After the mixture was allowed to cool to room temperature, it was filtered through celite (trademark), and the filtrate was concentrated under reduced pressure. The residue was diluted with a gas mixture, washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give Compound (1. 26 .1306016 nD21·6 1.5259 iHNMR(CDC13) δ 1.77-1.88 (m, 2H), 1.94-2.04 (m, 2H), 3.53-3.61 (m, 2H), 3.90-3.99 (m, 3 to 4H), 4.38- 4.45 (m, lH), 6.69 (t, 2H), 7.00 (d, lH), 7.04 (d, lH), 7.62 (d, lH), 8.39 (s, lH) Manufacturing Example 3 4-[4 Manufacture of -chloro-3-(3-trifluoromethyl)phenoxy]-l-[5-(triimethyl)_2-indenidinyl]-piperidine (Compound No. 1-15)

Under ice cooling, a third butyl nitrite (0.13 g) was added dropwise to a suspension of copper chloride (11) (0.14 g) in acetonitrile (5 ml). After the mixture was stirred for 1 Torr, a solution of the pyridine (Compound No. 1 _ 168 '0.35 g) obtained in Production Example 2 was added to acetonitrile (3 ml). After the mixture was warmed to room temperature, it was stirred for 2.5 hours. The mixture was poured into ice water and extracted with ethyl acetate. • The organic layer was washed with water and dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography to yield Compound (1. nD21 9 1.5275 'HNMRCCDCn) δ 1.82-1.92 (m, 2H), 1.99-2.08 (m, 2H), 3.60-3.68 (m, 2H), 3.89 - 3.97 (m, 2H), 4.56-4.63 (m, 1H) ), 6.69 (d, lH), 7.01 (d, lH), 7.24 (d, lH), 7.40 (d, lH), 7.63 (d, lH), 8.4 0 (s, lH)

27 .1306016 Production Example 4 Production of 4-[4-bromo-3-(3-trifluoromethyl)phenoxy]-1-[5·(trifluoromethyl)-2-yridinyl]-piperidine (compound) No. 1-23)

Under ice cooling, a third butyl nitrite (0.12 g) was added dropwise to a suspension of desert copper (II) (0-22 g) in acetonitrile (5 ml). The mixture was stirred for 1 • min. After the addition of the piperidine (Compound No. s 168, 〇. 32 g) in acetonitrile (2 ml) obtained in Preparation Example 2, the mixture was warmed to room temperature and then stirred. _ 5 hours. The mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by column chromatography to yield Compound (1. nD21.9 1.5365 *H NMR(CDC13) δ 1.8 1 -1.92 (m, 2H), 1-99-2.08 (m, φ 2H), 3.60-3.6 8 (ms2H), 3.88-3.96 (m, 2H) 54.5 7-4.63 (m, lH), 6.68 (d, lH), 6.94 (d, lH), 7.24 (s, lH), 7.58 (s, lH), 7.63 (d, 1H), 8.40 (s, 1H) Production Example 5 4 + -[4-bis(methylsulfonyl)amino]-3-(trifluoromethyl)phenoxy]-1-[5-trifluoromethyl-2-pyridyl]pyridine Manufacture of (Compound No. 1-1 78)

28 / 1306016 A solution of the piperidine (Compound No. 1 _ 168, 〇. 32 g) obtained in Example 2 in THF (5 ml) was added under ice-cooling, and decanesulfonium (〇〇9g) and triethylamine ( 0.08g). After the mixture was warmed to room temperature, it was stirred for 4 hours and then heated to reflux for 3.5 hours. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give Compound (1. Amorphous, H NMR (CDC13) δ 1.87-1.96 (m, 2H), 2.01-2.10 (m, 2H), 3.47 (s, 6H), 3.64-3.73 (m, 2H), 3.88-3.96 (m, 2H), 4.64-4.69 (m, lH), 6.70 (d, lH), 7.13 (dd, lH), 7.32 (d, lH), 7.37 (d, lH), 7.64 (d, lH), 8.41 (s) , lH) Production Example 6 4-[2-decyloxymethoxy-4-(trifluoromethyl)phenoxy]·[[5-trifluoromethylindolyl]? 1-105) Manufacturing

To a solution of 4-fluoro-3-hydroxybenzotrifluoride (〇36g) in DMF (5ml), 60% sodium hydride (88mg) was added, and chlorohydrazine (0.24g) was added dropwise under ice cooling. After the mixture was warmed to room temperature, it was stirred for 5 hours. The mixture 29 1306016 was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give crude compound (ll) (0.45 g). To a solution of piperidinol (12) (0.49 g) in DMF (5 mL) EtOAc. After the mixture was stirred for 1 minute, a solution of benzotrifluoro(11) in DMF (5 ml) was added, and the mixture was warmed to about 10 ° C and allowed to be stirred overnight. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography to yield Compound (1. nD23 9 1.4969 H NMR (CDC13) δ 1.87-1.96 (m, 2H), 2. 〇〇. 2.08 (m, 2H), 3.53 (s, 3H), 3.5 6-3.65 (m, 2H), 3.95· 4.03 (m, 2H), 4.61-4.65 (m, lH), 5.21 (s, 2H), 6.69 (d, lH), 7.02 (d, lH), 7.25 (d, lH) 57.3 8 (s, lH), 7.63 (d, lH), 8.40 (s, lH) Production Example 7 Repair of 4-[2-hydroxy_4_(trifluoromethyl)-phenoxy]jj5·(trifluoromethyl)_2-pyridyl] Manufacture of pyridine (Compound No. 1-4)

To a solution of the piperidine (Compound No. i_1〇5, 〇38 g) obtained in Example 6 in THF (5 ml), 1% hydrochloric acid (5mi) was added at room temperature. After the mixture was stirred for 2 hours, 1% hydrochloric acid (5 ml) was added and stirred overnight. The mixture 1306016 was poured into water and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give a compound of Compound No. 1-4 (0.3 lg). Viscous oil *H NMR (CDC13) δ 1.85 - 1.94 (m, 2H), 2.1 1-2.17 (m, 2H), 3.48-3.5 7 (m, 2H), 4.02-4.10 (m, 2H), 4.66- 4.70 (m, lH), 5.72 (s, lH), 6.70 (d, lH), 6.95 (d, lH), 7.13 (d, lH), 7.20 (s, lH), 7.65 (d, lH), 8.41 (s, lH) Production Example 8 4-[2-Ethyloxy-4-(trifluoromethyl)-phenoxy]trifluoromethyl)-2-pyridinyl]piperidine (Compound No. 1- 167) Manufacturing

To a solution of the acridine (Compound No. 1-1, 5, 0.17 g) obtained in Example 7 and triethylamine (50 mg) in acetonitrile (5 ml), hexane (36 mg). The mixture was warmed to room temperature and stirred for 3 hours, poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give Compound Compound 1-167 (0.22 g).

Mp.85-95〇C*H NMR(CDC13) δ 1.88 - 2.05 (m, 4H), 2.30 (s, 3H), 3.70-3.84 (m, 4H), 4.68 - 4.7 〇 (m, lH), 6.68 (d, lH), 7.05 (d, lH), 7.33 (s, lH), 7.47 (d, lH), 7.63 (d, 1 H), 8.39 (s, 1H) 31 1306016 Manufacturing Example 9 3_[4- Manufacture of (difluoromethyl)-phenoxydipyridinium-(trifluoromethyl)-2-pyridinyl]pyranone (Compound No. 8-63)

Using piromo alcohol (13) (〇35g) and 4-trifluorononylphenol (〇16g), the same procedure as in Example 1 was carried out to obtain a compound of compound No. 8_63.

(0.32g). Further, the compound (13) was prepared in the same manner as the compound (1?) of Production Example i. Mp.109-112°C . lH NMR (CDC13) δ 2.26-2.46 (m, 2H), 3.62- 3.75 (m, 2H), 3.85 (s, 2H), 5.10-5.15 (m, lH), 6.42 ( d, lH), 6.96 (d, 2H), 7.56 (d, 2H), 7.62 (d5lH), 8.3 9 (s, lH) Manufactured Example 10 2-Methyl-4-[2-propoxy-4- Process for the preparation of (trifluoromethyl)-phenoxy]·1-[5-trifluoromethyl-:2-D-pyridyl]-l-pyridine (Compound No. 1-93) 1 1 -Benzyloxy Manufacture of carbonyl-2-methyl-4-indolyl alcohol (14)

law. r? 1306016 In a solution of 4-methoxypyridine (2.5 〇g) in THF (25 ml), maintain _3 ° ° C ~ -20 ° C 'drip cerium magnesium bromide (3.0 M ether solution, 7.6 ml) ). After the mixture was stirred for 10 minutes, it was maintained at -30 to -20. (:, vinegar vinegar (3.90 g) was added dropwise. After the mixture was stirred for 30 minutes, the mixture was warmed to room temperature. The mixture was poured into 10% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with brine. Drying with magnesium sulfate, the solvent was evaporated under reduced pressure to give an oil (5.34 g), which was used directly for the next reaction. The following reaction was carried out according to J. 〇rg. Chem., 2001, 66, 2181. The oil was dissolved in acetic acid (150 ml), and the mixture was stirred at room temperature (2 1.4 g). The suspension was heated to reflux for 6 hours. After the mixture was cooled, it was passed through celite (registered trademark) and filtered. Distilled under reduced pressure, water was added to the residue, and the mixture was combined with EtOAc EtOAc. EtOAc. In a solution of the oil (2.47 g) in ethanol (25 ml), sodium borohydride (0.38 g) was added at room temperature, and the mixture was stirred for one hour. The mixture was reduced by pressure and concentrated with water. Ester extraction. The organic layer was washed with brine and dried over magnesium sulfate. Distillation to give the crude compound (14) (2.39 g). MH NMR (CDC13) 5 1.16-1.93 (m, 7H), 2.95-3.37 (m, lH), 3.88-4.70 (m, 3H), 5_13(m, 2H), 7.35 (m, 5H) Process 2 Manufacture of 1-benzyloxycarbonyl-2_methyl_4_[2-propoxy-4-[(trifluoromethyl)phenoxy]piperidine 33 1306016

In a solution of the compound (14) in DMF (25 ml), 60% at room temperature

Sodium hydride (0.42 g). After the mixture was stirred for 3 minutes, 4-fluoro-3-3 propyl benzodifluoride (2.13 g) was added to raise it to about 100 hrs and stirred overnight. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography to yield Compound (15) (102 g). 2.04(m,6H), 3.00-3.40(m,lH),3.92-4.16(m,3H),4.5 0- 4.73(m,2H),5.15(m,2H),6.93(m,lH),7.10 (m, 2H), 7.33 (m, 5H) Process 3 2-Mercapto-4-[2-propoxy-4-(trifluoromethyl)phenyloxy]-l-[5-(trifluoromethyl) Manufacture of bis-pyridinium acridine

Cf3 34 1306016 5% palladium-carbon (〇_20 g) was added to a solution of the compound (15) in ethanol (25 ml). The suspension was heated at 8 ° C for 8 hours in a hydrogen atmosphere. After cooling the mixture, it was filtered through diatomaceous earth (registered trademark). The filtrate was distilled off under reduced pressure to give a crude compound (16) (yield: 7 g). To the solution of the pyridine in acetonitrile (bml), 2- gas-5-(trifluoromethyl)oxime (4.0 g) and carbonic acid (1.53 g) were added and the mixture was heated to reflux for 3 days. After the mixture was cooled, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give Compound (1. Viscous oil lH NMR (CDC13) δ 1.04 (t, 3H), 1.23 (d, 3H), 1.71-1.97 (m, 4H), 2.10-2.26 (m, 2H), 3.05 (m, lH), 3.98 ( t, 2H), 4.43 (m, lH), 4.63 (m, lH), 4.88 (m, lH), 6.61 (d, lH), 7. 00-7.26 (m, 3H), 7.62 (d, lH) , 8.3 9(s, lH) Production Example 11 w 3d!-[2-Methoxy-4-(trifluoromethyl)phenoxy]-8-[5-(trifluoromethyl)-2-pyrene Manufacture of pyridine]_8_fluorene bicyclo[3.2.1]octane (Compound No. 2-77) 1 〇!-Hydroxy-δ-fluorene bicyclo [HI]octane acetate (18)

In a suspension of tropine (14.1 g), potassium carbonate (1.4 g) in benzene (150 ml), 35.1306016, 2,2,2-trichloroethyl chloroformate (23.3 g) was added at room temperature, and the mixture was heated. Reflux for 3.5 hours. After cooling the mixture to room temperature, it was poured into water and extracted with acetic acid. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give an oily carbonate (17) (30.08 g) which was used directly for the next reaction. Zinc powder (65 g) was added to the solution of the carbonate (丨7) in acetic acid (25 〇ml). After the mixture was stirred for 5 minutes, it was heated at 801 for 1 hour. After cooling the mixture to room temperature, it was passed through diatomaceous earth (registered trademark). The filtrate was concentrated under reduced pressure to give crude compound (18) (15.5 g). Process 2 3α-Hydroxy-8-[5_(trifluoromethyl)_2-pyridinyl]-8-fluorenylbicyclo[3.2.1]octane (19)

A suspension of the crude compound (5.64 g), potassium carbonate (41.5 g), and 2-chloro-5-trifluoromethylsulfonium hexahydrate (8.2 g) in acetonitrile was heated and refluxed for 3 to 5 hours. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, filtered, and evaporated. 'H NMR (CDC13) δ 1.42 (d, lH), 1.77 (d, 2H), 2.05-2.20 (m, 4H), 2.32-2.39 (m, 2H), 4.09 (brs, lH), 4.5 3 (brs , 2H), 6.52 (d, lH), 7.58 (dd, lH), 8.3 8 (d, lH) Process 3 3α-[2-methoxy-4-(trifluoromethyl)phenoxy]_8_[ 5-(trifluoromethyl)-2- 36 1306016 卩bite]-δ-^Τbicyclo[3·2·1] manufacture of smoldering f3c

OH

F 1) Mel 2) Compound (19)

To a solution of 4-fluoro-3-hydroxybenzotrifluoride (0.17 g) in DMF (3 mL) EtOAc. After the mixture was stirred for 20 minutes, methane (0.11 g) was added, and the mixture was warmed to 6 ° C and stirred for 4 minutes. After the 0 mixture was cooled to room temperature, compound 22 §) and 6 〇 0 / 〇 sodium hydride (35 mg) were added at room temperature and heated overnight. After cooling the mixture to room temperature, it was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield Compound (yield: Viscous oil 'H NMR (CDC13) δ 2.00-2.22 (m, 6H), 2.38- 2.44 (m, 2H), 3.90 (s, 3H), 4.56-4.61 (m, 3H), 6.56 • (d, 1H ), 6.77 (d, lH), 7.10 (S, lH), 7.16 (d, lH), 7.60 (dd, lH), 8.40 (b rd, lH). Production Example 12 3〇K2-propoxy-4- (Trifluoromethyl)phenoxy]_8_[5_(trifluoromethyl)_2-oxime ratio]-S-fluorene bicyclo[3.2.1]octane (compound No. 2_82) manufacturing process 1 8- Manufacture of methyl-3α-[2-propoxy-4-(trifluoromethyl)phenoxy]_8-fluorenebicyclo[3·2·1]octane (20) 37 •1306016

In a solution of 4_gas_3_p-benzotrifluoride (1.8 g) in DMF (15 ml), under ice A, 7 "60% sodium hydride (〇 44 g) was added. The mixture was stirred for 2 minutes. , force σ into 1-propane propane (1.7g) in DMF (3ml) solution, stir for 4 small days ^ at room temperature, add to the mixture of tropine (1.42g) and 60% sodium hydride _ (0'43g) 'The temperature was raised to 1 〇〇〇c and stirred for one night. After the mixture was cooled to room temperature, it was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. Concentration by pressure. The residue was purified by column chromatography to give the compound (20) (1. ig) as an oil. lR NMR (CDC13) δ 1.08 (t, 3H), 1.83 (q, 2H), 1.90 - 2.20 (m58H ), 2.30 (s, 3H), 3.10 - 3_ 11 (m, 2H), 3.95 (t, 2H), 4.58 (t, lH), 6.79 (d, lH), 7_05 (s, lH), 7.13 (d , lH) Process 2 φ 3α- [2-propoxy-4-(trifluoromethyl)phenoxy]_8_indole bicyclo[3.2.1]octane hydrochloride (22)

38 .1306016

CIC02CH(a)f

l~C02CH(C〇Me (21)

A solution of the compound (20) (1.Og) in dichloromethane (6 ml), m. The mixture was diluted with dioxane and washed with saturated aqueous sodium bicarbonate and brine. The solvent was distilled off under reduced pressure to give crude carbonate (21), which was used directly for the next reaction. To the compound (21), decyl alcohol (6 ml) was added, and the mixture was heated to reflux for 2.5 hours. The mixture was concentrated under reduced pressure to give crude compound (22), which was used directly for the next reaction. NMR NMR of the salt-free (22) (CDC13) δ 1.10 (t, 3H), 1.61 (brs, lH), 1.70_1.92 (m, 4H), 2. (H-2.09 (m, 4H), 2.20-2.31 (m, 2H), 3.52 (brs, 2H), 3.95 (t, 2H), 4.63-4.65 (m, lH), 6.78 (d, lH), 7.06 (s, lH), 7.15 (d, lH) Process 3 3α·[2-propoxy-4-(trifluoromethyl)phenoxy]_8_[5·(trifluoromethyl)-2-pyridyl]-8_吖bicyclo[3.2. 1] Manufacture of octane

39 1306016

0 shoulder (22) (23) A solution of crude (22), diethylamine (1.lSg) and 2_gas·5-trifluoromethylpropanidine (0.53 g) in ethanol (10 ml) was heated and refluxed overnight. Triethylamine (3 g), 2-gas-5-trifluoromethylpyridine (16 g) and ethanol (1 〇 ml) were added to the mixture, followed by heating under reflux for φ. After cooling the mixture to room temperature, it was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield compound (0.31 g). Mp.90-92. . !H NMR(CDC13) δ 1.09(t}3H), 1.82 - 1.93 (m, 2H), 2.01 - 2.23 (m, 6H), 2.43 - 2.50 (m, 2H), 3.97 (t, 2H), 4.56 - 4.62 (m, 3H), 6.55 (d, lH), Lu 6.77 (d, lH), 7.08 (s, lH), 7.15 (d, lH), 7.60 (dd, lH), 8.40 (s, lH) Example 13 8/3-[2-propoxy-4-(trifluoromethyl)phenoxy]_3_[5(trifluoromethyl)_2-pyridinyl]-3-indenyl[3.2.1] octane Process for the preparation of alkane (Compound No. 5-97) 1 N-Benzyl-8 heart [2-propoxy-4-(-trifluoromethyl)phenoxy]_3_indenyl[3.2.1]octane ( 25) Manufacturing: 1306016

N-Benzyl-3-indenylbicyclo[3.2.1]octane-8/3-ol was synthesized according to the method of J. Med. Chem. 2003, 46, 145 6-1464. To a solution of 4-fluoro-3-hydroxybenzotrifluoride (〇.5〇g) in DMF (4 ml) was added 60% sodium hydride (〇·12 g) under ice cooling. After the mixture was stirred at room temperature for 3 minutes, 1-iodopropane (0.51 g) was added. The solution was warmed to 90 ° C and stirred for 30 minutes. (24) (0.41 g) of DMF (4 ml) solution and 60% sodium hydride (9 g) were added to the mixture at room temperature. After stirring for 15 minutes, the mixture was heated to 1 〇 (TC) and stirred for 2 hours. After cooling to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. (25)(0.75g) 〇

*H NMR(CDC13) § 1.05(t,3H), 1.75- 1.91(m,6H), 2.19(dJ2H),2.3 4(brs52H), 2.74(d,2H),3.51(s,2H), 3.96( t, 2H), 4.33 (s, lH), 6.94 (d, lH), 7. 〇 7 (s, lH), 7.13 (d, lH), 7.2 0-7.34 (m, 5H) Process 2 8β- [ Manufacture of 2-propoxy-4-(trifluoromethyl)phenoxy]_ 3_[5-(trifluoromethylpyridinyl)·3·indenyl ring [3.2.1]octane

41 1306016

To a solution of the compound (25) (0.66 g) in ethanol (20 ml), palladium-carbon (0.13 g) was added. The suspension was stirred at room temperature under a hydrogen atmosphere - late. The mixture was filtered through celite (registered trademark), and the filtrate was evaporated under reduced pressure to give crude compound (26) (0.55 g). To a solution of the crude compound (26) (0.5 g) in acetonitrile (12 mL), EtOAc (EtOAc)

Heat reflux for 22 hours. After cooling the mixture, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield Compound (yield:

Mp. 4 8 - 5 0 ° C NMR (CDC13) δ 1.06 (t, 3H), 1.57 - 1.63 (m, 2H), 1.85 (sext, 2H), 2.03 - 2.06 (m, 2H), 2.57 (brs) , 2H) 53.08 (d52H), 3.98 (t52H), 4.15 (d, 2H), 4.63 (s, lH), 6.60 (d, lH), 7.01 (d, lH), 7.11 (s, lH), 7.18 ( d, lH), 7.62 (d, lH), 8.39 (s, l H) 42 1306016 Manufacturing Example 14

3〇ί-[2-Alkyl-4-(trifluoromethyl)phenoxy]_8_[5-(trifluoromethyl)-2-pyridine]-δ-fluorenylbicyclo[3·2·1]octane Manufacture of Compound No. 2_35)

To a solution of the compound (i9) (5 g) obtained in the procedure of Example 11 (m.), m. After the mixture was stirred at room temperature for 30 minutes, 4-fluoro-3-nitrobenzotrifluoride (3.84 g) was added. After the mixture was stirred at room temperature for 1 hour, the mixture was heated to 1 〇〇〇c and stirred overnight. After cooling the mixture to room temperature, it was poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield Compound (m. Viscous oil

NMR NMR (CDC13) δ 2.01-2.36 (m, 8H), 4.59 (brs, 2H), 4.75 (t, lH), 6.58 (d, lH), 7.01 (d, lH), 7.63 (d, lH), 7.76(d,lH),8,l 2(s,lH), 8.40 (s,lH) Example 15 3α-[2-Amino-4-(trifluoromethyl)phenoxy]_8·[5 -(Trifluoromethyl)-2-pyridinyl]-8-purine bicyclo[3.2.1] Simin (Compound No. 2-158) 43 1306016

To a solution of the compound of Compound No. 2-35 (2.14 g) in MeOH (24 ml), m. The mixture was stirred at room temperature for 1 hour. The mixture was filtered through celite (registered trademark), and the filtrate was evaporated under reduced pressure. ). Mp. 8 7 - 8 9 °C lH NMR (CDC13) δ 2.03 - 2.30 (m, 8H), 3.95 (s, 2H), 4.59 - 4.64 (m, 3H), 6.56 (d, lH), 6.62 (d , lH) 56.94 (s, lH), 6.96 (s, lH), 7.62 (d, lH), 8.41 (s5lH) Manufacturing Example 16

3〇f-[2-allyl-4-(trifluoromethyl)phenoxy]-8-[5-(trifluoromethyl)-2-hexidine]-8-fluorene bicyclo[3· 2_1]Manufacture of octane (Compound No. 2-62)

The following reaction was carried out in accordance with the method described in J. 〇rg. Chem., 2002, 67, 6376-6381. A small amount of the compound No. 2_158 obtained in Example 15 was added in a solution of butyl nitrite (0.18 g) and propyl bromide (2 lg) in acetonitrile (75 ml) at room temperature under a nitrogen atmosphere. (〇5g). After the mixture was stirred at room temperature for 3 hours, it was poured into water and extracted with ethyl acetate. The organic layer of 44 1306016 was washed with water and dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to yield compound (yield: 76 mg). Viscous oil Ή NMR (CDC13) δ 1.99- 5.15 6.69 (d, lH), 2.3 3 (m, 8H), 3.46 (d, 2H), 4.5 8 (brs, 3H), 5.08 (m, 2H), 5.94 -6.07 (m, lH), 6.57 (d, lH),

7.42 (brs, 2H), 7.62 (d, lH), 8.41 (s, lH) Manufactured Example 17 9/3-[2-methoxymethoxy-4-(trifluoromethyl)phenoxy]-3 -[5-(Trifluoromethyl)-2-pyridinyl]-3-indenylcyclo[3.3.1]nonane (Compound No. 7-1〇〇) Manufacturing Process 1 N-Benzyl_3_吖Manufacture of bicyclo[3.3.1]nonane-9-ol (29)

N-Benzyl-3-indenylbicyclo[3.3.1]nonane-9-one (28) was synthesized according to the method described in J. Med. Chem. 1994, 3 7, 2 831-2 840. To a solution of (28) (6.75 g) MeOH (EtOAc) After the mixture was stirred under ice cooling for 1 hour, the solvent was evaporated under reduced pressure. Water was added to the residue, which was extracted with methylene chloride, and the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give crude (29) (6.52 g). 45 1306016

Manufacture of 2 9-[2-oxiranyloxy_4_(trifluoromethyl)phenoxy]_3_benzyl_3_吖cyclo[3.3.1]decane (3〇), (31)

4-Fluoro-3-hydroxybenzotrifluoride (7.49 g) in a solution of DMF (75 mL). After the mixture was stirred at room temperature for 30 minutes, methylene ether (3.57 g) was added dropwise under ice cooling. The mixture was warmed to room temperature and stirred for 30 minutes, and further heated to 80 ° C and stirred for 30 minutes. Compound (29) (6.4 g) and 60% sodium hydride (1.33 g) were added to the mixture at room temperature for 30 minutes, and the mixture was heated to 10 ° C and stirred for 3 hours. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography to give compound (3 g) (6.3 g) and compound

(31) (4.25g). Compound (30): viscous oil NMR (CDC13) δ 1.43 - 1.60 (m, 3H), 2.01 - 2.08 (m, 4H), 2.36 (d, 2H), 2.65 - 2.80 (m, 1 H), 3.02(d,2H), 3.42(s,2H),3,5 3(s,3H),4.3 5(brs,lH),5.23(s,2H),6.93(d,lH),7· 21 - 7.33 (m, 8H) Compound (31): viscous oil! H NMR (CDC13) 5 1.46 - 1.55 (m, 1H), 1.68 - 1.80 (m, 2H), 1.91 - 1.97 (m, 2H), 2.09 ( Brd, 3H), 2.68 - 2.82 (s 46 1306016 plus m, 5H), 3.41 (s, 2H), 3, 54 (s, 3H), 4.31 (t, lH), 5.22 (s, 2H), 6.92 ( d,lH), 7.20 - 7.33 (m, 8H) Process 3 9-[2-methoxymethoxy-4-(trifluoromethyl)phenoxy]-3-[5-(trifluoromethyl) Manufacture of _2·pyridine]-3-indenylbicyclo[3.3.1]nonane (Compound No. 7-100)

To a solution of the compound (30) (6.1 g) in ethanol (180 ml), ι 〇〇 /. Palladium-carbon (1 · 22 g). The suspension was stirred at room temperature for 1 hour under a hydrogen atmosphere, and then the mixture was heated to 80 ° C and stirred for 7 hours. After the mixture was cooled to room temperature, it was filtered through celite (registered trademark), and the filtrate was evaporated under reduced pressure to give crude (32) (4.54 g) of crude compound (32) (4.54 g). To the mixture was added 2-chloro-5-(trifluoromethyl)pyridinium (ii.92 g) and potassium carbonate (10 g), and the mixture was heated to reflux overnight. After allowing the mixture to cool, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried with anhydrous sulfuric acid, and subjected to a transition and reduced pressure. The residue was purified by column chromatography to give Compound (1. Viscous oil 47 1306016 - 'H NMR (CDC13) <5 1.44 - 1.69 (m, 3H), 1.74 - 1.91 (m, lH), 2.08 - 2.21 (m, 2H) 52.32 (brs, 2H), 3.28 ( d, 2H), 3.54 (s, 3H), 4.47 (d, 2H), 4.62 (t, lH), 5.25 (s, 2H), 6.6 6 (d, lH), 7.02 (d, lH), 7.25 ( d, lH), 7.37 (s, lH), 7.63 (dd, lH), 8.42 (s, lH) Example 18 9jS-[2-hydroxy-4-(trifluoromethyl)phenoxy]-3- Manufacture of [5-(trifluoroindolyl)-2-pyridine]_3·indole bicyclo[3.3.1]nonane (Compound No. 7-4)

The compound (Compound No. 7-100) (2.54 g) obtained in Preparation Example 17 was obtained in the same manner as in Example 7. Mp. 108 -110°C Ή NMR (CDC13) δ 1.46 - 1.54 (m, 1 Η), 1.71 -

L_78(m,2H),1.82 - 1.93(m, 1 Η), 1.98 - 2.07(m,2H), 2.3 7(brs,2H),3.31(d,2H),4.51(d,2H), 4.70( t, lH), 5.81 (s, lH), 6. 68 (d, lH), 6.94 (d, lH), 7.12 (d, lH), 7.15 - 7.29 (m, lH), 7.65 (dd, lH) , 8.43 (s, lH) Example 19 9/5-[2-propoxy-4-(trifluoromethyl)phenoxy]-3-[5-(trifluoromethyl)-2-pyridine Manufacture of _3_吖二环[3.3.1] decane (Compound No. 7-82) 48 1306016

In a solution of DMF (15 ml), 6 〇% sodium hydride was added under ice-cooling. After stirring the mixture at room temperature for 30 minutes, iodine (0.13 g) was added under ice cooling, and the mixture was stirred at 30 ° The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, filtered and evaporated. Compound (〇.27g). Viscous oil lR NMR (CDC13) (5 1.09 (t, 3H), 1.45 - 1.49 (m, 3H), 1.55 - 1.93 (m, 3H), 2.16 - 2.30 (m, 4H) , 3.25(d,2H), 4.00(t,2H)54.45(d,2H),4.61(s,lH),6.65(d,lH),7.l(d,lH),7.12 - 7.24(m , 2H), 7.63 (dd, lH), 8.42 (s, lH) Example 20 3α-[2-propoxy-4-(trifluoromethyl)phenoxy]-8•oxytrifluoromethyl Manufacture of 8--8-bicyclo[3,2.1]octane (Compound No. 2-84)

A mixture of m-chloroperbenzoic acid (purity 65%, 0.28 g) was added to a solution of (Compound No. 2 - 82) (〇 48 g) obtained in Example 12 (d. After heating under reflux for 2 hours, the mixture was diluted with methylene chloride 49 1306016 and washed once with saturated aqueous sodium sulfite, aqueous potassium carbonate and brine. After drying over anhydrous magnesium sulfate, it was filtered and evaporated. The residue was purified by column chromatography to give Compound (yield: 28 g).

mp.l29-130〇C lH NMR(CDC13) δ 1.09(t,3H),1.82 - 1.94 (m,2H), 2.20 - 2.41 (m,8H), 3.77 (brs,2H),

3.97(t,2H), 4.54(t,lH)56.81(d,lH),7.08(s,lH),7.15(d,lH),7.36 (d,lH),7.86(dd,lH),8.48( s,lH) Example 21 3〇f-[2-propoxy-4-(trifluoromethyl)phenoxy]_8- [5-(trifluoromethyl)-2-pyridyl-1-oxo Manufacture of ]_8_吖二环[3·2·1]octane (Compound No. 2-83)

Pyridine-N-oxide (33) was synthesized according to the method described in J. Heterocycl. Chem. 1976, 13, 41-42. To a suspension of (22) (0.65 g) of acetonitrile (6 ml) obtained in Example 13 was added pyridine-N-oxide (33) (0.395 g) and carbonated (0-82 g). After the mixture was cooled, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sulfuric acid, filtered, and concentrated under reduced pressure to give compound (sup.88 g). 50 1306016

mp.l43-145〇C Ή NMR(CDC13) 5 l.〇8(t,3H),1.83-1.90(m,2H), 2.04-2.15(m,4H),2.25-2.31(m,2H), 2.44-2.48(m,2H), 3.97(t,2H),4.68(brs,lH),5.02(brs,2H)56.79-6.84(m,2H),7.08(s,lH),7.15(d,lH ), 7.23 - 7.33 (m, lH), 8.39 (s, lH) Example 22

Cis-3-methyl-4-[2-propoxy-4-(trifluoromethyl)phenoxy]·丨·[5_(trifluoromethyl)-2-acridinyl acridine (compound number 1_97) Manufacturing Process 1

Cis-3-methyl-1·[5_(trifluoromethyl)_2_indolyl]cyclopropanol (Μ) and trans-3_mercapto-1-[5_(difluoroindolyl)_2_ ratio η Manufacture of base_____α-alcohol (36)

Indole-benzyl 3-methyl-4 piperidone (34) is a compound known in the literature and is commercially available. To the compound (34) (2 - 53 g) was added sodium hydride (yield: 47 g) under ice cooling. After a period of 'under ice cooling' in a solution of 丨〇% hydrochloric acid (CAS. No. 34737-89-8) in EtOH (40 ml), the mixture was neutralized at room temperature 2 51 1306016. The mixture was extracted with dichloromethane, and the organic layer was dried over anhydrous sulfuric acid. The solvent was distilled off under reduced pressure to give crude (35) (2 27 g). To a solution of the crude (35) (1.82 g) in methanol (30 ml), 2? The suspension was heated to 70 C under a hydrogen atmosphere and stirred for 1 day. After cooling the mixture to room temperature, pass through the diatomaceous earth (Registry); consider adding 20% NaOH to the solution, _ carbon (〇.9g), warm to 70 C and stir for one night. After the mixture was cooled to room temperature, it was filtered through celite (registered trademark), and the filtrate was evaporated under reduced pressure to give crude (36) (22 g), which was used directly for the next reaction. (3) (1.22 g) To a solution of acetonitrile (5 〇ml), 2-gas-5-(trifluoromethyl)pyridinium (2.3 g) and potassium carbonate (4.4 g) were added, and the mixture was heated to reflux overnight. The mixture was poured into water and extracted with EtOAc. EtOAc (EtOAc) 38) (0.55g) 〇

(3 7): yellow oily 'H NMR (CDC13) δ 1.01 (d, 3H), 1.59 (brs, lH), 1.77-1.94 (m, 3H), 3.21 (t, lH), 3.44 - 3.53 (m) , lH), 3.85 - 3.98 (m, 3H), 6.65 (d, lH), 7.5 8 (dd, lH), 8.37 (s, lH) (3 8): yellow oily NMR (CDC13) δ 1.07 ( d,3H),1.46-1.63 (m,3H), 2.00-2.07 (m,lH), 2.65 (t,lH), 3.02 (t,lH), 3.40 - 3.47 (m, 1 H), 4.26-4.40 (m, 2H), 6.66 (d, lH), 7.60 (dd, lH), 8.37 (s, 1H) 52 1306016 Process 2 cis-3-indolyl-4-[2-propoxy-4-(three Preparation of fluoromethyl)phenoxy]-1-[5-(trifluoromethyl)_2-pyridyl]piperidine (Compound No. 1-9)

60% sodium hydride (23 g) was added to a solution of the compound (38) (〇, 15 g) in DMF (4 ml). The mixture was warmed to 70 ° C, and 4-fluoro-3-propoxybenzotrifluoride (〇 14 g) was added and heated at 1 ° C overnight. After the mixture was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give Compound (1. nD22·8 1.5000 lR NMR (CDC13) δ 1.05 (t, 3H), 1.12 (d, 3H), 1.71-1.92 (m, 4H), 2.02 - 2.08 (m, 2H), 3.40 (t-like, 1 H ), 3.5 1 (t-like, lH), 3.95 - 4.05 (m, 3H), 4.55 (brs-like, 1H), 6.67 (d, lH), 7. 〇〇 (d, lH), 7. 8(d,lH),7.16(d,lH), 7.61(dd,lH), 8.39(s,lH) Production Example 23 3〇!-[2-Butyl-4-(trifluoromethyl) Manufacture of phenoxy]_8_[5-(trifluoroindolyl)_2-dipyridyl]-8-fluorenylbicyclo[3.2.1]octane (compound No. 2-187) 53 1306016 Process 1 3«-{2 -(Π,3]dioxolanyl)_4_(trifluoromethyl)phenyloxy} 8_[5_(trifluoromethyl)-2-pyridyl]_8-fluorenyl[m]octane (compound) No. 2_ 169) Manufacturing

2-fluoro-5-(difluoroindolyl)benzaldehyde (5 〇〇g), ethylene glycol (178 g) and

A solution of the toluene acid monohydrate (0.49 g) in benzene (50 ml) was refluxed for one night. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, and filtered and evaporated to give the crude compound (39) (5.81 g). In a solution of crude (39) (2.00 g) and compound (i9) (2.30 g) in DMF (20 ml), 60% sodium hydride (〇.50 g) was added in 5 portions at 80 °C. The mixture was stirred at 80 ° C for 1 hour directly. After cooling to room temperature, it was poured into ice water and extracted with EtOAc. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield Compound (yield: 3.24 g).

mp.l48-151〇C*H NMR(CDC13) δ 2.01-2.14(m,4H),2.24-2.3 7(m,4H),4.04-4.20(m,4H),4.5 8(brs,2H), 4.63(t,lH), 6.17(s,lH), 6.57(d,lH), 6.75(d,lH),7.5 5(dd5lH), 7.62(dd,lH),7.84(d,lH), 8.41(s,lH) 54 1306016 Process 2 3α:-[2-Methylthio-4_(trifluoromethyl)phenoxy]_8_[5-(trifluoromethyl)_2_indolyl]_8-mouth Manufacture of the second ring [3.2.1] Xin Shao (4丨)

Under ice cooling, a solution of the compound (40) (3.24 g) in THF (100 ml) was added with hydrochloric acid (1 〇〇mi). The mixture was warmed to room temperature and stirred for 2 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with aq. 10% aqueous sodium sulfate and brine and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give (41) (2 - 95 g). NMR (CDC13) δ 2.04-2.39 (m,8H), 4.64 (brs, 2H), 4.78 (t,lH), 6.60 (d,lH), 6.92 (d,lH), 7.65 (dd,lH), 7.77 (dd,lH), 8.15(s,lH), 8.42(s,lH),l〇.53(s,lH)

3α-[2-(1-Hydroxybutyl)-4-(trifluoromethyl)phenoxy]·8_[5·(trifluoromethyl)_2-pyridinyl]_8_吖bicyclo[3.2. 1] octane (42) was produced at 〇 ° C, and a solution of n-propyl magnesium bromide in THF (1 - 02 mol / l) was added dropwise to a solution of the compound (41) (1.83 g) in THF under a nitrogen atmosphere ( After 6.06 ml), the temperature was raised to room temperature and mixed for 2 hours. The mixture was poured into a saturated aqueous solution of sulfuric acid and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield (42) (0.96 g).

55 1306016

mp.l41-145〇C !H NMR (CDC13) δ 0.98 (t, 3H), 1.41-1.60 (m, 2H), 1.71-1.81 (m, 2H), 1.98-2.04 (m, 3H), 2.16- 2.37 (m, 5H), 4.59-4.62 (m, 3H), 5.09-5.14 (m, lH), 6.5 7 (d, lH) 5 6.70 (d, lH), 7.46 (dd, lH), 7.63 (dd3lH ), 7.74 (s, lH), 8.41 (s, lH) Process 4 3o: -[2-( Butan-1-yl)-4-(trifluoromethyl)phenoxy]-8-[5-( Manufacture of trifluoromethyl)_2-pyridyl]-8-fluorene bicyclo[3.2.1]octane (43)

A solution of the compound (42) (0.40 g) and p-toluenesulfonic acid monohydrate (0.14 g) in toluene (4 ml) was heated to reflux overnight. After cooling the mixture to room temperature, it was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give Compound (43) (0.37 g). mp.94-98〇C Ή NMR(CDC13) δ 1.14(t,3H),2_00-2.32(m,10H),4.58-4.63(m,3H),6.26-6.35(m,lH),6.5 7 ( d,lH),6.69- 6.77(m,2H), 7.40(d,lH), 7.62(dd,lH), 7.69(s, 1 H),8.41 (s, 1H) Process 5 3α-[2-丁Manufacture of keto-4-(trifluoromethyl)phenoxy]-8-[5-(trifluoromethyl)-2-pyridyl]-8-fluorenyl[3·2·1]octane 56 1306016 (43)

To a solution of the compound (43) (0.22 g) in ethanol (6 ml), 5 〇 / 〇 palladium _ carbon (0.04 g) was added. The suspension was stirred at room temperature under a hydrogen atmosphere for one night. The mixture was filtered through diatomaceous earth (registered trademark), and the filtrate was depressurized. The residue was purified by column chromatography to give the objective compound (?? Mp.86-88〇C lR NMR(CDC13) (5 〇.96(t,3H),1.35-1.47 (m,2H), 1.54-1.66 (m,2H), 1.97-2.03 (m, 2H), 2.10-2.14 (m, 2H), 2.21-2.32 (m, 4H), 2.64 (t, 2H), 4.54-4.56 (m, 3H), 6.51 (d, lH), 6.60 (d, lH), 7.33 ( d, lH), 7.34 (s, lH), 7.56 (dd, lH), 8. 31 (s, lH) Manufacturing Example 24

Manufacture of 4-[2-propoxy-4-(trifluoromethyl)phenylthio]445-(trifluoromethyl)_2-pyridyl]-octane (Compound No. 9.94) Process 1 1-Benzyl Manufacture of oxy-2-propoxy-4-(trifluoromethyl)benzene (44)

1) nPrf 2) Bn〇H

To a solution of 4-fluoro-3-hydroxybenzotrifluoride (1.80 g) in DMF (20 ml), 60% sodium hydride (t. 44 g) was added under ice cooling, and the mixture was warmed to room 57 1306016 and stirred 30 After a minute, a solution of 1-iodopropane (1.87 g) in DMF (5 mL) was added. The mixture was warmed to 80 ° C and stirred for 30 minutes. After cooling the mixture to room temperature, benzyl alcohol (2.16 g) and 60% sodium hydride were added, and the mixture was warmed to 80 ° C and stirred for 30 minutes. The mixture was cooled to room temperature, poured into ice water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield Compound (44) (2.95 g). ]H NMR(CDC13) δ 1.07(t,3H),1.82-

L_94(m,2H), 4.00(t,2H),5_18(s,2H),6.92(d,lH),7.09-7_14(m,2H),7.28-7.44(m,5H) Process 2 2_C Manufacture of oxy-4-(trifluoromethyl)benzenethiol (46)

To a solution of the compound (44) (2.95 g) in ethanol, 10% palladium-carbon (0.59 g) was added, and the suspension was stirred overnight at room temperature under a hydrogen atmosphere. The mixture was filtered through celite (registered trademark), and the filtrate was evaporated under reduced pressure. The crude compound (45) (2.0 lg) was obtained. From the crude compound (45) (2. Olg), according to the method described in J. Med. Chem. 2002, 45, 3972-3983, compound (46) (1.82 g) was obtained. !H NMR(CDC13) δ 1 · 10(t,3H),1.84-1 _96(m,2H), 4_07(t,2H),7_01(s,lH),7.09(d,lH),7.32(d , lH) 58 1306016 Process 3 Manufacture of 4-bromo-1-[5·(trifluoromethyl)-2-inthyl]piperidine (48)

Triethylamine (〇.45 g) and methanesulfonium chloride (0.51 g) were added to a solution of the compound (12) (1.00 g) in EtOAc (10 ml), and the mixture was warmed to room temperature. After stirring for 30 minutes, it was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. To a solution of the crude compound (47) (1.32 g),jjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj After cooling the mixture, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield Compound (48) (0.74 g). NMR NMR (CDC13) δ 1.99-2.10 (m, 2H), 2.16-^ 2.25 (m, 2H), 3.5 5-3.62 (m, 2H), 3.91-4.00 (m, 2H), 4.42-4.49 (m, lH), 6.66 (d, lH), 7.63 (dd, lH), 8.3 9 (s, lH) Process 4 4-[2-propoxy-4-(trifluoromethyl)phenylthio]-l- Manufacture of [5-(Trifluoromethyl)-2-pyridinyl]-piperidine

59 1306016

BrHC/H'Al)_CF3(48)

To a solution of the compound (46) (0-62 g) in DMF (7 ml), 60% sodium hydride was added under ice cooling, and the mixture was warmed to room temperature and stirred for 30 minutes. Compound (48) (0.74 g) was added to the mixture, followed by heating to 100 T: and stirring for 1 hour. After cooling the mixture, it was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give the title compound ( s. Viscous oil 'H NMR (CDC13) δ 1.09 (t, 3H), 1.63-1.75 (m, 2H), 1.84-1.95 (m, 2H), 2.04_2.10 (m, 2H), 3.19-3.2 8 ( m,2H),3.54· 3.62(m,lH),4.03(t,2H),4.21-4.28(m,2H),6.64 (d,lH),7.04(s,lH),7.16(d,lH) , 7.40 (d, lH) 57.61 (dd, lH), 8.3 8 (s, Production Example 25 3α-[2-propoxy-4-(trifluoromethyl)phenylthio]_8_[5_(trifluoromethyl) )) 卩 卩 α α ] ] ] ] ] ] 3 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ ]_8_吖二环[3.2.1]Manufacture of octane (50) 1306016

MeOjSO

Cf3 (19) (49) Λ 0

(50)

Triethylamine (1.12 g) and methanesulfonate (1.26 g) were added to a solution of the compound (19) (2. g) in dioxane (2 mL) and stirred for 30 min. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to give crude compound (49) ( 2.29 g). Add ruthenium acetate (1.88g) to a solution of the crude compound (49) (2.29g) in DMF (35ml), warm up to 10 (rc, stirring for one night. After cooling the mixture to room temperature, pour into water, with acetic acid The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated.

H NMR (CDC13) § 1.66-1.75 (m, 2H), 1.87- 2.18 (m, 9H), 4.61 (brs, 2H), 5.25-5.36 (m, lH), 6.5 7 (d, lH), 7.62 ( Dd,lH), 8.41 (s, lH) Process 2 3α-[2-propoxy-4-(trifluoromethyl)phenylthio]_8_[5-(trifluoromethyl)-2-pyridyl]-8 ·吖二环[3.2.1]Manufacture of octane 1306016

To a solution of the compound (50) (1.15 g) in methanol (25 ml), EtOAc (EtOAc) After cooling, 'methanol was distilled off under reduced pressure' and water was added, and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude compound (5 1) (1.00 g). To a solution of the crude compound (51) (1.00 g) and the compound (46) (〇.87 g) in toluene (l?ml) was added triphenylphosphine (i.93 g) and azodicarboxylic acid diisopropyl vinegar. (1 _ 4 9 g) 'After the temperature to give a night. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give the desired compound (yel. 39 g).

mp.72-74〇C lR NMR(CDC13) δ 1-〇7(t,3H)51.83- 1.92(m,4H),2.1 Β-2.1 7(m,2H),2.35-2.5 5(m,4H ), 3.69 (t, lH), 4.01 (t, 2H), 4.5 7 (brs, 2H), 6.51 (d, lH), 7. 02 (s, lH), 7.15 (d, lH), 7.26 (d) , lH), 7.60 (d, lH), 8.38 (d, lH) Production Example 26 3α-[2-isopropyl-aminooxy-4-(trifluoromethyl)phenoxy]trifluoro

62 • 1306016 %* • Methyl)-2_pyridyl]_8_吖bicyclo[3_2·1]octane Manufacture (Compound No. 2-212) Process 1 3oK2-methoxymethoxy_4_(trifluoro Manufacture of methyl phenoxy]_8_[5·(yl)_2_% pyridine]-δ-fluorene bicyclo[3·2.ι]octane (52) Fluorine

1) CICH20Me 2) (19) 伢3 In a solution of 4-fluoro-3-hydroxybenzotrifluoride (2.48 g) in DMF (30 ml), 60% sodium hydride (0.59 g) was added under ice cooling. After the mixture was stirred at room temperature for 30 minutes, methyl ether (8 g) was added dropwise under ice cooling. The mixture was warmed to room temperature and stirred for 30 minutes and then warmed to 80. (: After stirring for 30 minutes. To the mixture, compound (19) (2.50 g) and 60% sodium hydride (0.55 g) were added at room temperature, and after stirring for 30 minutes, the mixture was heated to 100 ° C and stirred for 2 hours. After cooling to room temperature, it was poured into water and extracted with EtOAc EtOAc EtOAc (EtOAc) ) (3.98g).

mp.69-73〇C !H NMR(CDC13) δ 2.01-2.25(m,6H), 2.37-2.44 (m,2H),3.54(s,3H),4.57-4.63(m,3H)55.23(s , (2, H), 6.

V 1306016, Process 2 3α-[2-P--4-(trifluoromethyl)phenyloxy]_8_[5•(trimethyl)_2, pyridine]-δ-ρ丫bicyclo[3· 2_ι]Manufacture of Xinyuan (53)

Using the compound (N) (3 - 98 g), the compound (53) (3.61 g) was obtained in the same manner as in Example 7.

Mp.90-94 〇C,H NMR(CDC13) d 2.03-2.34^,8^,4.61 (brs,2H),4.67(t,lH),5.8 8(s,lH),6.5 8(d,lH ),6_73(d,lH),7.11( d,1 Η),7·21 (s,lH),7.63(dd,1H),8.41(s,1H) Process 3 3»-[2-isopropylidene Manufacture of Amino Oxo 4-(trifluoromethyl)phenoxy]_8_[5-(trifluoromethyl)-2-pyridyl]-8-fluorenebicyclo[3.2.1]octane

Using the compound (53) (1.0 g), the compound (54) (0.54 g) was synthesized according to the method described in JP-A-2001-81071. To a solution of the compound (54) (yield: 25 g) in ethanol (2 ml), acetone (mi) and concentrated hydrochloric acid (0.03 g) were added, and the mixture was stirred at room temperature for 1 hour. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous sulphuric acid < The residue was purified by column chromatography to give the desired compound (0.20 g).

Mp.l07-109〇C lR R(CDC13) δ 2.01-2.28(m,12H), 2.40- 2.48(m,2H),4.56(brs,2H),4.64(t,lH),6.55(d, lH), 6.78 (d, lH), 7. % 19 (dd, lH) 57.61 (dd, lH), 7.70 (d, lH), 8.40 (s, lH) Manufacturing Example 27 3o:-[2-(2 -Methylpropenyloxy)_4_(trifluoromethyl)phenoxy]_8_[5-(trifluoromethyl)-2-pyridinyl]-8-indole bicyclooctane (Product No. 2-245 Process 1 3〇:-[2-(2-methylallyloxy)_4_(trifluoromethyl)phenoxy]_8_[5 (trifluoromethylpyridinyl)_8-fluorene bicyclic [HI ]Manufacture of octane (55)

To a solution of the compound (53) (0, 50 §) in DMF (5 ml), 6 % of sodium hydride (G_G5g) was added under ice cooling. After the mixture was stirred at room temperature for 3 G minutes, it was added with a solution of propylidene chloride (〇 14 g) and sodium hydride (〇 23 g) under ice cooling. The mixture was warmed to room temperature and stirred for 3 minutes and then warmed to 8 Torr. . And stirring

65 1306016

1 hour. The mixture was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography to yield Compound (55) (. mp.96-98〇C 'H NMR(CDC13) δ l-87(s,3H), 2.01-2.24(m,6H),2.41- 2.47(m52H),4.47(s,2H),4.5 6(brs , 2H), 4.61 (t, lH), 5.03 (s, lH), 5. 16 (s, lH), 6_56 (d, lH), 6.78 (d, lH), 7.10 (s, lH), 7.16 ( d,lH),7_60( dd,lH), 8.40(s,lH)

3a-[2-(2-Methylpropenyloxy)-4-(trifluoromethyl)phenoxy]_8_[5-(trifluoromethyl)-2-pyridinyl]_8_吖bicyclo[3.2_1 Manufacture of octane

A solution of the compound (55) (0.42 g) in DMSO was added to a third butoxide (0.11 g) and stirred at 1 ° C for 5 hours. The mixture was cooled to room temperature and poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate] The residue was purified by column chromatography toieldield (0.19 g).

Mp.90-92 〇C 'H NMR (CDC13) 5 1.73 (d, 6H), 2.01-2.24 (m, 6H), 2.41 - 2.48 (m, 2H), 4.56 (brs, 2H), 4.63 (t, lH), 6.20 (s, lH), 6.56 (d, lH), 6. 80 (d, lH), 7.17-7.22 (m, 2H), 7.61 (dd, lH), 8.40 (s51H) 66 1306016 Manufacturing Example 28 5_Trifluoromethyl 2_1 {3»-[5_(trifluoromethyl) D-pyridyl]·8_ 丫 bicyclo[3.2.1]octyl-3-oxobenzoic acid furan-2 -Production of a base ester (Compound No. 2_244) Process 1 3仏[2-Cyano-M-trifluoromethyl)phenoxy]-8-[5-(trifluoromethyl)_2_ptt pyridine]_8_吖Manufacture of bicyclo [3.2.1] octane (56)

To a solution of the compound (19) (3.698) in ^(3〇1111), 60% sodium hydride (〇. 71 g) was added under ice cooling. The mixture was stirred at room temperature for 3 minutes and 4-chloro-3-cyanobenzotrifluoride (2.78 g) was added. The mixture was stirred at room temperature for 30 minutes and heated to 1 ° C for 4 hours. The mixture was cooled to room temperature, poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give Compound (56) (4.24 g). Mp. 110 -113 °C 'H NMR (CDC13) δ 2.01-2.45 (m, 8H), 4.60 (brs, 2H), 4.74 (t, lH), 6.5 9 (d, lH), 6.91 (d, lH) 57.63 (dd, lH), 7.77 (dd, lH), 7.86 (s, lH), 8.41 (s, lH) Process 2 5_Trifluoromethyl-2-{3α-[5-(trifluoro Methyl)pyridinyl;j_8-fluorene bicyclol 67 .1306016 [3.2.1]octyl_3_oxy}methane formic acid furan ester

9.

To a solution of the compound (56) (4.24 g) in ethanol (10 ml) was added potassium hydroxide (5_3 8 g). The mixture was cooled to room temperature, poured into water, neutralized with hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The crystals thus obtained were dissolved in acetic acid (22 ml), and sodium nitrite (〇.99 g) and concentrated sulfuric acid (3.59 g) were successively added in a small amount in the solution under ice cooling. The mixture was warmed to /l and allowed to mix for 5 hours. The mixture was poured into ice water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate]]]]]]]] Thiopurine chloride (〇17g) was added dropwise to THF (2mi) at a temperature below 30C, and stirred for 10 minutes, and the resulting solution was added dropwise to a solution of compound (57) (0.2 g) in THF (4 ml). Further, triethylamine (〇22g) was added. The mixture was warmed to room temperature and stirred for 3 minutes. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to give the title compound (m. 68 .1306016 mp.85-8 8〇C 'H NMR(CDC13) δ 2-〇l-2.23(m,10H),2.3 5-2.47 (m,2H),4.56(brs,2H),4.66(t , lH), 6.54-6.59 (m, 2H), 6.84 (d, lH), 7.60-7.68 (m, 2H), 7.96 (s, lH), 8.41 (s, lH) Manufacturing Example 29 3o; -[2 -(2-methyloxazol-5-yl)-4_(trifluoromethyl)phenoxy]·8_[5_(difluoromethyl)-2_teptyl]-8-purine bicyclic [ 3·2·1] Manufacturing of Xin Shao (Compound No. 2-214)

3a-[2-(2-methyl-[1.3]-oxapentan-2-yl)-4-(trifluoromethyl)phenyloxy]-8-[5·(trifluoromethyl)_2 Manufacture of _pyridyl]-8-fluorene bicyclo[3·2·ι]octane (61) CH0

(58)

(59)

To a solution of 2-fluoro-5-trifluorodecylbenzaldehyde (3.0 g) in THF (30 mL), EtOAc (EtOAc) The mixture was warmed to room temperature, stirred for 30 minutes, poured into a saturated aqueous solution of ammonium sulfate and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate]]]]]]]]

(58) (3.42 g) 二 To the gas-like solution of the crude compound (58) (3.42 g), sulphuric acid (6.78 g) was added, and the suspension was stirred under heating and reflux for 2 hours. After the suspension was cooled to room temperature, it was filtered through diatomaceous earth (registered trademark). The mash was concentrated under reduced pressure to give a crude compound (59). To a solution of the crude compound (59) (1.00 g) in benzene (m.m.), hexanes (0-66 g) and p-toluenesulfonic acid monohydrate (9 g) were stirred and stirred under reflux for 5 hours. After cooling the mixture to room temperature, it was poured into water and the mixture was weighed with acetic acid. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, filtered, and evaporated,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, 60% sodium hydride (0.18 g) was added under ice cooling. After the mixture was stirred at room temperature for 30 minutes, the crude compound (60) (1·13 g) was added. The mixture was stirred at room temperature for 3 minutes and then heated to 100 ° C for 8 hours. The mixture was cooled to room temperature and poured into water and extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The residue was purified by column chromatography to yield Compound (61) (0.55 g). *H NMR(CDC13) δ 1 ·81 (s,3H), 2.01-2.12 (m, 4H), 2.25- 2.33 (m, 2H), 2.46-2.53 (m, 2H), 3.77-3.88 (m, 2H) ), 4.01-4.13 (m, 2H), 4.57-4.5 8 (m, 3H), 6.5 7 (d, lH), 6.73 (d, lH), 7.50 (dd, lH), 7.62 (dd, lH), 7.81 (s, lH), 8.42 (s, lH) Process 2 3α-[2-(2-Methyloxazole-5-yl)_4_(trifluoromethyl)phenoxy]-8-[5-( Manufacture of trifluoromethyl)_2·pyridyl]-8-fluorene bicyclo[3.2.1]octane 1306016

6N Hydrochloric acid (2 1 mmol) was added to a solution of the compound (jjjjjjl The mixture was poured into water, neutralized with an aqueous solution of sodium hydroxide and then extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. Using the crude compound (62) (0.30 g), the title compound (0.20 g) was obtained according to the method of J. Heterocyclic Chem., 1998, 35, 1533-1534.

mp.l21-123〇C 'H NMR(CDC13) δ 2.04-2.28(m,6H),2.34- 2.42(m,2H), 2.39(s,3H)s4.59(brs,2H)J4.71( t, lH), 6.58 (d, lH) 6. 83 (d, lH) 57.50 (dd5lH) 57.52 (s5lH), 7.63 (dd5lH), 7.96 (s, lH), 8.4 2 (s, lH) Table 1~ Table 14 is a specific example of the compound of the present invention comprising the above examples. The scope of the invention is not limited to the embodiments and specific examples. The abbreviations in the table are as follows. Vis: Sticky paulownia.

71 1306016

Compound No. R1 R2 R3 R4 R5 R51 R6 Physical constant []: Melting point °C Remark 1-1 4-0H 5-CF3 HHHHH nD 22.2-1.5499 1-2 3-OH 5-CF3 HHHHH 1-3 2-OH 5- CF3 HHHHH 1-4 2-0H-4-CF3 5-CF3 HHHHH vis 1-5 4-F 5-CF3 HHHHH 1-6 3-F 5-CF3 HHHHH 1-7 2-F 5-CF3 HHHHH 1-8 2-F-4-CF3 5-CF3 HHHHH [72-74] 1-9 3-CF3-4-F 5-CF3 HHHHH nD 23.1-1.5071 1-10 4-C1 5-CF3 HHHHH [90-92] 1 -11 3-C1 5-€F3 HHHHH 1-12 2-C1 5-CF3 HHHHH 1-13 2-C1-4-CF3 5-CF3 HHHHH nD 21.8-1.5210 1-14 3-C1-4-CF3 5- CF3 HHHHH 1-15 3-CF3-4-C1 5-CF3 HHHHH nD 21.9-1.5275 1-16 2,6-C12-4-CF3 5-CF3 HHHHH [65-66] 1-17 2-Br-4- CF3-6-Cl 5-CF3 HHHHH '[71-73] 1-18 2-Cl-6-〇nPr-4-CF3 5-CF3 HHHHH [70-72] 1-19 4-Br 5-CF3 HHHHH [ 87-90] 1-20 3-Br 5-CF3 HHHHH 1-21 2-Br 5-CF3 HHHH . H 1-22 2-Br-4-€F3 5-CF3 HHHHH nD 21.8-1.5320 1-23 3- CF3-4-Br 5-CF3 HHHHH nD 21.9-1.5365 1-24 4-1 5-CF3 HHHHH 1-25 3-1 5-CF3 HHHHH 1-26 2-1 5-CF3 HHHHH 1-27 2-I-4-CF3 5-CF3 HHHHH VB 1-28 2-CF3-4-I 5-CF3 HHHHH 1-29 4-CN 5-CF3 HHHHH [ 157-161] 1-30 3-CN 5-CF3 HHHHH 1-31 2-CN 5-CF3 HHHHH 1-32 2-CN-4-CF3 5-CF3 HHHHH Q01-102] 1-33 2-CF3-4 -CN 5-CF3 HHHHH 73 1306016 Table 1 (Continued)

Compound No. R 1 R2 R3 R4 R5 R51 R6 Physical constant []: Melting point °c Remarks 1-34 4-N02 5-CF3 HHHHH [140-144] 1-35 3-N02 5-CF3 HHHHH 1-36 2-N02 5-CF3 HHHHH 1-37 2-C1-4-CF3-6-N02 5-CF3 HHHHH [69-70] 1-38 2-N02-4-CF3 5-CF3 HHHHH [96-97] 1-39 3 -CF3-4-N02 5-CF3 HHHHH VB 1-40 2-CH0-4-CF3 5-CF3 HHHHH [85-90] 1-41 4-Me 5-CF3 HHHHH 1-42 3-Me 5-CF3 HHHHH 1-43 2-Me 5-CF3 HHHHH 1-44 2, 4_Me2 5-CF3 HHHHH nD 22.3-1.5410 1-45 2-Me-4-CF3 5-CF3 HHHHH 1-46 2_Me-4-0CF3 5-CF3 HHHHH nD 24.4-1.5089 1-47 2, 4, 6-Me3 5-CF3 HHHHH nD 22.2-1.5339 1-48 2~Me-4-F 5-CF3 HHHHH nD 24.3-1,5373 1-49 2-Me-4_Cl 5-CF3 HHHHH nD 22.9-1.5505 1-50 2~Me_4~Br 5-CF3 HHHHH 1-51 2-Et-4_CF3 5-CF3 HHHHH 1-52 2-Me-4_C1 5-CF3 HHHHH 1-53 2_Me-4_Br 5-CF3 HHHHH 1-54 2-Et-4-Cl 5-CF3 HHHHH nD 24.6-1.5445 1-55 2-Et-4-CF3 5-CF3 HHHHH 1-56 2-Et-4-0CF3 5-CF3 HHHHH 1-57 2-nPr-4-Cl 5-CF3 HHHHH nD 24.9-1.5394 1-58 2-nPr-4-Br 5-CF3 HHHHH 1-59 2-nPr-4-CF3 5-CF3 HHHHH nD 22.5-1.5141 1-60 2-iPr-4-CF3 5-CF3 HHHHH 1 -61 2-^^4-01 5-CF3 HHHHH 1-62 2-iPr-4-Br 5-CF3 HHHHH 1-63 2-CH20Me-4-CF3 5-CF3 HHHH . H nD262-L5U0 1-64 2 -CH20Me-4-Cl 5-CF3 HHHHH 1-65 2-CH20Me-4-Br 5-CF3 HHHHH 1-66 2-CH20Et-4-CF3 5-CF3 HHHHH nD 23.3-1.5090 1-67 2-CH (0H Et-4-CF3 5-CF3 HHHHH vis 1-68 2-CH20H-4-CF3 5-CF3 HHHHH vis 1-69 2-CH20CH20Me-4-CF3 5-CF3 HHHHH VE 1-70 3-CH20CH20Me-4- CF3 5-CF3 HHHHH 1-71 2-CH20CH20Et-4-CF3 5-CF3 HHHHH nD 22.5-1.5069 1-72 2-CH20CH(Me)0Me- 4-CF3 5-CF3 HHHHH nD 22.6-1.5018

74 1306016 Table l (Continued)

Compound No. R 1 R 2 R3 R4 R 5 R51 R 6 Physical constant []: Melting point °c Remark 1-73 2-CH=CHMe-4-CF3 5-CF3 HHHHH [68-71] 1-74 2-allyl- 4-CF3 5-CF3 HHHHH vis 1-75 4-CF3 5-CF3 HHHHH [48-50] 1-76 3-CF3 5-CF3 HHHHH nD 23.1-1.5151 1-77 2-CF3 5-CF3 HHHHH 1-78 3, 4-(CF3)2 5-CF3 HHHHH 1-79 3,5-(CF3)2 5 - CF3 HHHHH nD21.6-l.4889 1-80 2, 4-(CF3)2 5-CF3 HHHHH vfe 1-81 2-CH2C1-4-CF3 5-CF3 HHHHH VB 1-82 2-CH(Cl)Et-4-CF3 5-CF3 HHHHH VB 1-83 4-CF3 3-C1-5-CF3 HHHHH nD 23.0 -1.5150 1-84 4-CF3 4-Me-6-CF3 HHHHH nD 23.2-1.5089 1-85 4-0Me 5-CF3 HHHHH [86-88] 1 -86 3-0Me 5-CF3 HHHHH 1 -87 2- OMe 5-CF3 HHHHH 1 -88 2-0Me-4-CF3 5-CF3 HHHHH nD 22.8-1.5150 1 -89 2-0Et-4-CF3 5-CF3 HHHHH [50-53] 1 *90 2-0Et-4 -CF3 5-C1 HHHHH VB 1 -91 2-0Et-4-CF3 5-Br HHHHH [39-41] 1 -92 2-0nPr-4-CF3 5-CF3 HHHHH [55-65] 1 -93 2- 〇"Pr-4-CF3 5-CF3 Me HHHH VB 1 -94 2-0nPr-4-CF3 5-Me HHHHH nD21.4-l.5295 1 -95 2-OnPr-4-CF3 5-CF3 HH Me C02Et H VB 1 ^96 2-0nPr-4-CF3 5-CF3 HHHHH HD 22.2-1.4834 N - oxide Essence 1) 1 -97 2-〇nPr- 4-CF3 5-CF3 HH Me HH nD 22.8-1.5000 cis 1 -98 2-0nPr-4-CF3 5-CF3 HH Me HH vis trans 1 -99 2-OnPr-5-CF3 5-CF3 HHHHH nD 22.4-1.5088 1-100 2-OiPr-4-CF3 5-CF3 HHHHH nD 25.3-1.5060 1-101 2-OnBu-4-CF3 5-CF3 HHHHH [70-74] 1-102 2-〇iBu-4-CF3 5- CF3 HHHHH [103-104] 1-103 2-〇nHex-4-CF3 5-CF3 HHHHH [68-73] 1-104 2-0nPen-4-CF3 5-CF3 HHHH · H 1-105 2-0CH2OMe- 4-CF3 5-CF3 HHHHH nD 23.9-1.4969 1 -106 2-0CH20Et-4-CF3 5-CF3 HHHHH 1-107 2-0CH20nPr-4-CF3 5-CF3 HHHHH 1-108 2-0CH2cPr-4-CF3 5 -CF3 HHHHH [49-51] 1-109 2-0CH2cPr-4-CF3 5-C02Me HHHHH 1 -110 2-0CH2cPr-4-CHF2 5-CF3 HHHHH 1-111 2-0CH2cPr-4-CH0 5-CF3 HHHHH 1-112 2-0CH2cPr-4-CF3 5-CN HHHHH 1-113 2-OCH2cPr-4-CN 5-CF3 HHHHH 1-114 2-00Η2ιΒυ-4-0Ρ3 5-CF3 HHHHH VB Note 1)

75 11306016 Table 1 (Continued)

Compound No. R 1 R2 R3 R4 R5 R51 R6 Physical constant []: Melting point °c Remark 1 -115 2-0(CH2)20Me-4-CF3 5-CF3 HHHHH [51-54] 1 -116 2-0 (CH2 20Me-4-CF3 5-CN HHHHH 1-117 2- 0(CH2)20CH20Me- 4-CF3 5-CF3 HHHHH VB 1-118 2-0(CH2)20H-4-CF3 5-CF3 HHHHH nD 22.2- 1.5121 1 -119 2-0CH2Ac-4-CF3 5-CF3 HHHHH 1-120 2-0CH2CH(0H)Me- 4-CF3 5-CF3 HHHHH 1-121 2-0CH2CH(0Me)Me-4-CF3 5-CF3 HHHHH 1-122 2-0CH2C(0H)Me2-4-CF3 5-CF3 HHHHH 1 -123 2-0CH2C(OMe)Me2-4- CF3 5-CF3 HHHHH 1-124 2-0CH2C(Me2)C02Me-4- CF3 5-CF3 HHHHH 1-125 2-0CH2C (0)0Me-4-CF3 5-CF3 HHHHH 1-126 2-0CH2C(0)0Et-4-CF3 5-CF3 HHHHH 1-127 2-0(CH2) 20Ac-4-CF3 5-CF3 HHHHH 1 -128 2-0(CH2)2NH2-4- CF3 5-CF3 HHHHH 1 -129 2-0(CH2)2NHAc-4-CF3 5-CF3 HHHHH 1-130 2- 0(CH2)2NMe2-4-CF3 5-CF3 HHHHH 1-131 2-0CH2CH(Cl)Me- 4-CF3 5-CF3 HHHHH 1 -132 2OCH2CH=CMe2TM4-CF3 5-CF3 HHHH · H 1-133 4-OCF3 5-CF3 HHHHH [30-32] 1 -134 3-0CF3 5-CF3 HHHH H 1 -135 2-0CF3 5-CF3 HHHHH 1 -136 4-0CF2Br 5-CF3 HHHHH VB 1 -137 3-0CF2Br 5-CF3 HHHHH 1 -138 2-0CF2Br 5-CF3 HHHHH 1 -139 2-0 (CH2 ) 2Br-4-CF3 5-CF3 HHHHH [82-84] 1-140 2-0(CH2)2Cl-4-CF3 5-CF3 HHHHH vis 1 -141 2-0(CH2)2F-4-CF3 5- CF3 HHHHH 1 -142 2-Oallyl-4-CF3 5-CF3 HHHHH [75-77] 1-143 2-Oallenyl-4-CF3 5-CF3 HHHHH vis 76 1306016 Table 1 (Continued)

Compound No. R1 R2 R3 R4 R5 R51 R6 Physical Constant []: Melting Point °C Remark 1 444 4-C02Me 5-CF3 HHHHH [124-126] 1145 3-C02Me 5-CF3 HHHHH 1146 2-C02Me 5-CF3 HHHHH 1 447 4-SCF3 5-CF3 HHHHH [81-82] 1448 3-SCF3 5-CF3 HHHHH 1 449 2-SCF3 5-CF3 HHHHH 1150 4-S(0)CF3 5-CF3 HHHHH [83-86] 1 451 3- S(0)CF3 5-CF3 HHHHH 1 452 2-S(0)CF3 5-CF3 HHHHH 1 i53 4-0S02CF3 5-CF3 HHHHH [52-54] 1 i54 3-0SQ2CF3 5-CF3 HHHHH 1 455 2-0S02CF3 5-CF3 HHHHH 1 456 4~<T (6) Ph 5-CF3 HHHHH [154-156] 1 457 3-0C(0)Ph 5-CF3 HHHHH 1 458 2-OC (9) Ph 5-<F3 HHHHH 1 459 4-€CH2Ph 5-CF3 HHHHH [109-110] li60 3-〇CH2Ph 5-CF3 HHHHH 1 461 2-0CH2Ph 5-CF3 HHHHH 1 i62 4-OCH2(Naph-l-yl) 5-CF3 HHHHH &23 -124] 1 i63 2-〇propargyl-4- m 5KF3 HHHHH vis 1 464 2-(0CH2CH=0C12)- 4-CF3 5-CF3 HHHHH [93-95] 1 i65 2,3,6-C13-4- 0CH2CH=0C12 3-C1-5-CF3 HHHHH [58-60] 1 466 2,3, fr~C13-4-OCH2CH=OC12 5-CF3 H HHHH VB 1 467 2-〇Ac*4-CF3 5-CF3 HHHHH [85-95] 1 468 3-CF3-4-NH2 5-CF3 HHHHH nD21.6-l.5259 1 469 2-NH2-4-CF3 5-CF3 HHHHH vis 1470 2-NH2-4-CF3-6-C1 5-CF3 HHHHH vis 1 471 2-MWe-4-CF3 5-CF3 HHHHH 1 472 2.t-4-CF3 5-CF3 HHHHH VB 1 I73 2-MfPr-4-CF3 5-CF3 HHHHH vis lm 5-CF3 HHHHH nD 22.0-1.5121 1 i75 2-N (Ac) ^4-(33⁄4 5-CF3 HHHHH Q10-114] 77 1306016 Table 1 (Continued) )

Compound No. R1 R2 R3 R4 R5 R51 R6 Physical constant []: Melting point °C Remark 1-176 2-0C (9) 0Me-4-CF3 5-CF3 HHHHH nD 23.9-1.5000 1-177 2-OC(9)SMe-4-CF3 5- CF3 HHHHH [77-79] 1-178 3-CF3-4- N(S02Me)2 5-CF3 HHHHH amor 1-179 2-C(0)Et-4-CF3 5-CF3 HHHHH vis 1-180 2- CH20- tetrahydrofuran- 2-vl-4-CF3 5-CF3 HHHHH nD 22.7-1.5105 1-181 2-(1, 3-dioxolanyl)-4-CF3 5-CF3 HHHHH nD 23.2-1.5155 1-182 2-€H20nPr -4-CF3 5-CF3 HHHHH [67-70] 1-183 2-CH20CH20Me-4-CF3 5-CF3 HH Me HH nD 22.2-1.5062 cis:trans= 1:1 1-184 2-CH(Me)0CH20Me - 4-CF3 5-CF3 HHHHH nD 23.7-1.4995 1-185 2-CH20CH(Me)Et- 4-CF3 5-CF3 HHHHH Nd24.ll.5015 1-186 2-〇nPr-4CF3 5-CF3 HH Et HH Vis cis 1-187 2-OnPr-4-CF3 5-CF3 HH Et HH vis trans 1-188 2-CH20CH(Me)0Me- 4CF3 5-CF3 HH Me HH nD 23.2-1.5035 trans 1-189 2-CH20CH( Me)0Me-4CF3 5-CF3 HH Me HH nD 24.6-1.5039 cis 1-190 2-(3-Me-l,2,4-oxadiazol-5-yl)-4-CF3 5-CF3 HHHHH VB 1-191 2-〇nPr-4-CF3 5-CF3 HH nPr HH nD22.3-l.5055 Cis 1-192 2-〇nPr-4-CF3 5-CF3 H H nPr H H VB trans 78

1306016' Table 2 Μ A

Compound No. R1 R2 Physical constant "1: Melting point °c Remark 2-1 4-OH 5-CF3 2-2 3-OH 5-CF3 2-3 2-OH 5-CF3 2-4 2-OH-4-CF3 5-CF3 [90-94] 2-5 4-F 5-CF3 2-6 3-F 5-CF3 2-7 2-F 5-CF3 2-8 2-F-4-CF3 5-CF3 2- 9 3-CF3-4-F 5-CF3 2-10 4-C1 5-CF3 2-11 3-C1 5-CF3 2-12 2-C1 5-CF3 2-13 2-C1-4-CF3 5- CF3 vis 2-14 3-CF3-4-C1 5-CF3 2-15 2, 6-C12-4-CF3 5-CF3 2-16 2-Br-4-CF3-6-Cl 5-CF3 2-17 2-Cl-6-〇nPr-4-CF3 5-CF3 2-18 4-Br 5-CF3 2-19 3-Br 5-CF3 2-20 2-Br 5-CF3 2-21 2-Br-4 -CF3 5-CF3 [112-115] 2-22 3-CF3_4_Br 5-CF3 2-23 4-1 5-CF3 2-24 3-1 5-CF3 2-25 2-1 5-CF3 2-26 2 -I-4-CF3 5-CF3 2-27 4-CN 5-CF3 2-28 3-CN 5-CF3 2-29 2-CN 5-CF3 2-30 2-CN-4-CF3 5-CF3 [ 110-113] 2-31 4-N02 5-CF3 2-32 3-N02 5-CF3 2-33 2-N02 5-CF3 2-34 2-C1-4-CF3-6-N02 5-CF3 79 1306016 Table 2 (Continued)

Compound No. R1 R2 Physical constant f 1: Melting point °C Remarks 2-35 2-N02-4-CF3 5-CF3 vis 2-36 3-CF3-4-N02 5-CF3 2-37 2-CHO-4-CF3 5-CF3 2-38 4"Me 5-CF3 2-39 3-Me 5-CF3 2-40 2-Me 5-CF3 2-41 2, 4~Me2 5-CF3 2-42 2 - Me-3* ~CF3 5-CF3 [121-123] 2-43 2-Me-4-CF3 5-CF3 2-44 2-Me-4-0CF3 5-CF3 [88-91] 2-45 2-Et-4* ~CF3 5-CF3 2-46 2, 4, 6-Me3 5-CF3 2-47 2-Me-4-F 5-CF3 [98-100] 2-48 2-Me-4-Cl 5-CF3 2 -49 2-Et-4-Cl 5-CF3 2-50 2-nPr-4-Cl 5-CF3 2-51 2-nPr-4-CF3 5-CF3 vis 2-52 2"Pr-4-CF3 5 -CF3 2-53 2-CH20Me-4-CF3 5-CF3 2-54 2-CH20Et-4-CF3 5-CF3 [91-93] 2-55 2-CH(OH)Et-4-CF3 5-CF3 2-56 2-CH20H-4-CF3 5-CF3 2-57 2-CH20CH20Me-4-CF3 5-CF3 vis 2-58 2-CH20CH20Et-4-CF3 5-CF3 vis 2-59 2-CH20CH(Me) 0Me-4-CF3 5-CF3 [89-91] 2-60 2-CH20CH(Me)0Me-4-CF3 5-CF3 [95-98] N-oxide (Note 2-1) 2-61 2-CH =CHMe~4-CF3 5-CF3 2-62 2-allyl-4-CF3 5-CF3 vis 2-63 4-CF3 5-CF3 2-64 3-CF3 5-CF3 2-65 2-CF3 5-CF3 2-66 3, 4-(CF3)2 5-CF3 2-67 3, 5-(CF3)2 5-CF3 VB 2-68 2, 4-(CF3)2 5-CF3 2-69 2-CH2C1-4-CF3 5-CF3

80 1306016 Table 2 (Continued)

Compound No. R 1 R 2 Physical constant []: Melting point °c Remarks 2-70 2-CH(Cl)Et-4-CF3 5-CF3 2-71 4-CF3 3-C1-5-CF3 2-72 4- CF3 4-Me-6-CF3 2-73 4-OMe 5-CF3 2-74 3-0Me 5-CF3 2-75 2-OMe 5-CF3 2-76 2-OMe-4-CN 5-CF3 [85 -90] 2-77 2-0Me-4-CF3 5-CF3 vis 2-78 2-0Et-4-CF3 5-CF3 vis 2-79 2-0Et-4-CF3 5-C1 2-80 2-0Et -4-CF3 5-Br 2-81 2-0nPr-4-CN 5-CF3 vis 2-82 2-0nPr-4-CF3 5-CF3 [90-92] 2-83 2-0nPr-4-CF3 5 -CF3 [143-145] N-oxide (Note 2-2) 2-84 2-0nPr-4-CF3 5-CF3 [129-130] N-〇xide (Note 2-3) 2-85 2-0nPr -4-CF3 5-C1 [92-97] 2-86 2-0"Pr-4-CF3 5-Br [50-52] 2-87 2-0nPr-4-CF3 5-N02 [159-160] 2-88 2-0nPr-4-CF3 5-NH2 am or 2-89 2-0nPr-4-CF3 5-Me [97-98] 2-90 2-0"Pr-4-CF3 5-NHS02Me am or 2-91 2-0nPr-5-CF3 5-CF3 2-92 2-0"Pr-4-CF3 6-CF3 nD22.5-l.5090 2-93 2-0nPr-4-CF3 5-CN [124 -125] 2-94 2-0nPr-4-CF3 5-CF3-6-CN [132-134] 2-95 2-Cl-6-〇nPr-4-CF3 5-CF3 vis ' 2-96 2- 〇iPr-4-CF3 5-CF3 [113-115] 2-97 2-0nBu-4-CF3 5-CF3 [53-55] 2-98 2-0iBu-4-CF3 5- CF3 [126-129] 2-99 2-0nHex-4-CF3 5-CF3 2-100 2-〇nPen - 4"CF3 5-CF3 vis 2-101 2-0CH2CN-4-CF3 5-CF3 vis 2- 102 2-0CH20Me-4-CF3 5-CF3 [69-73] 2-103 2-0CH20Et-4-CF3 5-CF3 2-104 2-0CH20nPr-4-CF3 5-CF3 2-105 2-0CH2cPr-4 -CF3 5-CF3 [114-116] 2-106 2-〇CH2cPr-4-CF3 5-C02Me 2-107 2-0CH2cPr-4-CHF2 5-CF3 2-108 2-〇CH2cPr-4-CH0 5- CF3 2-109 2-0CH2cPr-4-CF3 5-CN

81 1306016 Table 2 (Continued)

Compound No. R1 R2 Physical constant "1: Defective note 2-110 2-0CH2cPr-4-CN 5-CF3 2-111 2-00Η2ιΒυ-4-0Ρ3 5-CF3 [148-150] 2-112 2-0 ( CH2)20Me-4-CF3 5-CF3 VE 2-113 2-0(CH2)20Me-4-CF3 5-CN 2-114 2-0(CH2)20CH20Me-4-CF3 5-CF3 2-115 2- 0(CH2)20H-4-CF3 5-CF3 VB 2-116 2-0CH2Ac-4-CF3 5-CF3 2-117 2-0CH2CH(0H)Me-4-CF3 5-CF3 2-118 2-OCH2CH( OMe)Me-4-CF3 5-CF3 2-119 2-0CH2C(0H)Me2-4-CF3 5-CF3 2-120 2-0CH2C(0Me)Me2-4-CF3 5-CF3 2-121 2-0CH2C (Me2)C02Me-4-CF3 5-CF3 2-122 2-0CH2C(0)0Me-4-CF3 5-CF3 2-123 2-0CH2C(0)0Et-4-CF3 5-CF3 2-124 2- 0(CH2)20Ac-4-CF3 5-CF3 2-125 2-0(CH2)2NH2-4-CF3 5-CF3 2-126 2-0(CH2)2NHAc-4-CF3 5-CF3 2-127 2 -0(CH2)2NMe2-4-CF3 5-CF3 2-128 2-0CH2CH(Cl)Me-4-CF3 5-CF3 2-129 2-0CH2CH=CMe2-4-CF3 5-CF3 2-130 2- 0CH2CH(Me)0Me-4-CF3 5-CF3 VB 2-131 4-0CF3 5-CF3 2-132 3-0CF3 5-CF3 2-133 2-0CF3 5-CF3 2-134 4-0CF2Br 5-CF3 2 -135 3-0CF2Br 5-CF3 2-136 2-0CF2Br 5-CF3 2-137 2-0(CH2)2Br-4-CF3 5-CF3 2-138 2-0(CH2)2Cl-4-CF3 5-CF3 vis 2-139 2-0(CH2)2F-4-CF3 5-CF3 2-140 2-0CH2(Ph-4-Cl)-4-CF3 5-CF3 [115-118] 2-141 2 -〇allyl-4-CF3 5-CF3 vis 2-142 2-〇al1eny1-4-CF3 5-CF3 2-143 2-〇propargyl-4-CF3 5-CF3 vfe 2-144 2-0(CH2)2CH =CH2-4-CF3 5-CF3 VB 2-145 2-0CH2CH=CHMe-4-CF3 5-CF3 [65-67] Mixture of cis and tr ans 2-146 2-0CH2CH=CMe2-4-CF3 5- CF3 [54-57] 2-147 2-0CH2C(Me)=CH2-4-CF3 5-CF3 [96-98] 82 1306016

Table 2 (Continued) Compound No. R1 R2 Physical constant "1: Melting point °c Remarks 2-148 2-0CH2CH=CHCl-4-CF3 5-CF3 vis ci s mixture with trans 2-149 2-0Ac-4- CF3 5-CF3 [93-97] 2-150 2-0C(0) ^-4^3 5-CF3 [112-115] 2-151 2-0S02Me-4-CF3 5-CF3 [107-110] 2 -152 2-0S02Et-4-CF3 5-CF3 [121-124] 2-153 2-S02nPr-4-CF3 5-CF3 am or 2-154 2-0S02nBu-4-CF3 5-CF3 [133-136] 2-155 2-0S02NMe2-4-CF3 5-CF3 [140-143] 2-156 2-0C(S)NMe2-4-CF3 5-CF3 [150-153] 2-157 2-SC(0)NMe2 -4-CF3 5-CF3 [165-168] 2-158 2-NH2-4-CF3 5-CF3 [87-89] 2-159 2-N(nPr)2-4-CF3 5-CF3 am or 2 -160 2-NHnPr-4-CF3 5-CF3 [94-96] 2-161 2-N(Me)nPr-4-CF3 5-CF3 vis 2-162 2-NHS02Me-4-CF3 5-CF3 [165 -168] 2-163 2-NHS02Et-4-CF3 5-CF3 [171-174] 2-164 2-N(S02nBu)2-4-CF3 5-CF3 [181-183] 2-165 2-S" Pr-4-CF3 5-CF3 [87-90] 2-166 2-SCH2cPr-4-CF3 5-CF3 [110-112] 2-167 2-0P(0) (0Et)S"Pr-4-CF3 5-CF3 VB 2-168 2-〇nPr-4-CF3 1, 3-Me2-pyrazolyl-5-vl [132-134] 2-169 2-(1,3-dioxolanyl)-4-CF3 5-CF3 [148-151] 2-170 2-CH(Me)0C H20Me-4-CF3 5-CF3 nD 23.7-1.5045 2-171 2-CH20nPr-4-CF3 5-CF3 nD 23.7-1.5137 2-172 2-0CH2Ac-4-CF3 5-CF3 Nd24.l-1.5263 2-173 2-0CH2CH(0H)Me-4-CF3 5-CF3 am or 2-174 2-0CH2CH(0Me)Me-4-CF3 5-CF3 [105-108] N-oxile (Note 2-4) 2-175 2-0CH2CH(0Et)Me-4-CF3 5-CF3 Nd22.8-l.5138 2-176 2-0CH2CH(0S02Me)Me-4-CF3 5-CF3 Nd22.9-1.5092 2-177 2-0CH( Me)Et-4-CF3 5-CF3 [89-91] 2-178 2-0CH(Me)CH20Me-4-CF3 5-CF3 [56-58] 2-179 2- (〇-tetrahydofuranyl-3-vl )-4-CF3 5-CF3 [91-93]

83 1306016 Table 2 (Continued)

Compound No. R 1 R2 Physical constant "1: Melting point °C Remarks 2-180 2-CH20H-4-CF3 5-CF3 [115-118] 2-181 2-0CH2CH(F)Me-4-CF3 5-CF3 [ 99-102] 2-182 2-0CH2SMe-4-CF3 5-CF3 [76-80] 2-183 2-0CH2C(=CH2)Cl-4-CF3 5-CF3 [83-85] 2-184 2- CH(OH)nPr-4-CF3 5-CF3 [141-145] 2-185 2-CH(0Me)nPr-4-CF3 5-CF3 Nd24.9-1.5070 2-186 2-CH=CHEt-4- CF3 5-CF3 [94-98] Mixture of cis and trans 2-187 2-nBu-4-CF3 5-CF3 [86-88] 2-188 2-CH=CHC02Et-4-CF3 5-CF3 [107- 110] a mixture of ci s and trans 2-189 2-CH2CH2CH20H-4-CF3 5-CF3 am or 2-190 2-CH2CH2CH20Me-4-CF3 5-CF3 Nd22.5-1.5249 2-191 2-CH2CH2CHO-4- CF3 5-CF3 Nd22.6-1.5335 2-192 2-CH2CH2CH(OMe)Me-4-CF3 5-CF3 Nd22.6-l.5110 2-193 2-C02Et-4-CF3 5-CF3 [94-98 2-194 2-CH(0H)sBu-4-CF3 5-CF3 [121-124] 2-195 2-0CH2CH(Br)Me-4-CF3 5-CF3 [114-119] 2-196 2- C02iPr-4-CF3 5-CF3 [95-97] 2-197 2-CH(0H)CH2tBu-4-CF3 5-CF3 [179-181] 2-198 2-C02tBu-4-CF3 5-CF3 [118 -120] 2-199 2- (4-Me-oxazoli zi ny1-2-vl)-4-CF3 5-CF3 [102-106] 2-200 2-(3-Me-l,2,4-oxadiazoy L-5-yl)-4-CF3 5-CF3 [148-151] 2-201 2-(5-Me-〇xazolizinyl~2- vl)-4-CF3 5-CF3 [105-107] 2-202 2-(5-Me-l,3, 4-oxadiazolyl-2-yl)-4-CF3 5-CF3 [177-179] 2-203 2-CH=N0Et-4-CF3 5-CF3 am or (E 2-204 2-C02CH2C^CH-4-CF3 5-CF3 [95-97] 2-205 2- (5-Me-oxazoly1^2-yl)-4-CF3 5-CF3 [120-122] 2 -206 2-C02CH(Me)CsCH-4-CF3 5-CF3 [111-113] 2-207 2-〇nPr-4-CF3 3-C1-5-CF3 K4-25] 2-208 2-C02sBu~ 4-CF3 5-CF3 [92-94] 2-209 2- (4-Me-〇xazolyl-2-yl) -4 - CF3 5-CF3 [100-103] 2-210 2- (4, 4~ Me2-oxazolizinyl-2-yl)-4-CF3 5-CF3 [122-124] 2-211 2-CH=N0Me-4-CF3 5-CF3 [92-94] 84 1306016 Table 2 (Continued)

Compound No. R1 R2 Physical constant "1: Melting point °c Remarks 2-212 2-0N=C(Me)2-4-CF3 5-CF3 [107-109] 2-213 2-0N=CHMe-4-CF3 5 -CF3 [64-66] E, Z mixture 2-214 2-(2-Me-〇xazolyl-5-yl)-4-CF3 5-CF3 [121-123] 2-215 2-CH=NOiPr-4 -CF3 5-CF3 Γ110-1121 2-216 2-(5~Me-l, 2, 4-oxadiazolyl-2-yl)-4-CF3 5-CF3 [174-177] 2-217 2-(5- 〇Me~oxazolyl-2-vl)-4-CF3 5-CF3 [143-146] 2-218 2-C(Me)=NOEt-4-CF3 5-CF3 Γ91-94] (E) 2-219 2 -C(Me)=NOEt-4-CF3 5-CF3 Γ92-96Ι (2) 2-220 2-(4-Et-〇xazolizinyl-2- vl)-4-CF3 5-CF3 [95-99] 2 -221 2-CH=N0CH2C Tri-CH-4-CF3 5-CF3 [96-98] 2-222 2-N=C(Me)0Me-4-CF3 5-CF3 [81-83] (E) 2- 223 2-C02cPen-4-CF3 5-CF3 [66-68] 2-224 2-N=C(Me)0Et-4-CF3 5-CF3 vis <E) 2-225 2-C02- (tetrahydrofuranyl- 3- vl)-4-CF3 5-CF3 [94-96] 2-226 2-0N=C(Me)Et-4-CF3 5-CF3 "77-801 E, Z Mixture 2-227 2 - ON= (cyclopentylidenyl)-4-CF3 5-CF3 [96-98] 2-228 2-0N=CHEt-4-CF3 5-CF3 Nd22.2-l.5170 E, Z mixture 2-229 2~ 0N=(cyclohexylidenyl )-4-CF3 5-CF3 [99-103]. 2-230 2-C02CH2CH20Me-4-CF 3 5-CF3 Nd22.5-l.5159 2-231 2-C02cHex-4-CF3 5-CF3 Nd22.4-1.5042 2-232 2-C02CH(Me)iPr-4-CF3 5-CF3 Nd22.4- 1.5083 2-233 2-C02CH(Me)CH2C1-4-CF3 5-CF3 Nd22.4--l.5105 2-234 2-C02CH(Me)CH20Me-4-CF3 5-CF3 Nd22.8-1.5065 2- 235 2-C02CH(Me)CH=CH2-4-CF3 5-CF3 [77-81] 2-236 2-C02CH(Me)CH2Br-4-CF3 5-CF3 [94-98] 2-237 2-C02CH2cPr -4-CF3 5-CF3 [90-94] 2-238 2-C02cPr-4-CF3 5-CF3 [143-145] 2-239 2-C02CH(Me)cPr-4-CF3 5-CF3 [123- 125] 2-240 2-C02CH2CF3-4-CF3 5-CF3 [83-86] 85 1306016

Table 2 (Continued) Compound No. R1 R2 Physical Constant []: Melting Point °c Remark 2-241 2-〇C(〇)〇iRr4-(E3 [38-42] 2-242 2-<mN=C( ^e)2r4-m 5-CF3 [110-112] 2-243 2-M]〇2iPr-4-CF3 5<F3 [140-143] 2-244 2-00&- (tetiBhydrofurarr 2t1)^F3 5 -CF3 [85-88] 2-245 2-0CH=C(Me)2-4-CF3 5-CF3 [90-92] 2-246 2-0CH2CHF2^-CF3 5-CF3 [85-87] 2- 247 2~002CH〇ife)ai=a^-CF3 5-(73 [119-121] N-oxite (Note 2-5) 2-248 (4) amfe^KF3 5-CF3 D.0&-108] 2- 249 2K3^(3^)CH2CMe-4-CF3 5-CF3 [58-62] e) 2-250 2-CN=C(Me)CMe-l-CF3 5-CF3 [120-122] ¢) I ' ο 86 1306016 Table 3 (Dn~〇r2 Compound No. R 1 R2 Physical Constant []: Melting Point °C Remarks 3-1 4-0H 5-CF3 3-2 3-OH 5-CF3 3-3 2-0H 5- CF3 3-4 2-0H-4-CF3 5-CF3 3-5 4-F 5-CF3 3-6 3-F 5-CF3 3-7 2-F 5-CF3 3-8 2-F-4- CF3 5-CF3 3-9 3-CF3-4-F 5-CF3 3-10 4-C1 5-CF3 3-11 3-C1 5-CF3 3-12 2-C1 5-CF3 3-13 2-C1 -4-CF3 5-CF3 3-14 3-CF3-4-C1 5-CF3 3-15 2, 6-C12-4-CF3 5-CF3 3-16 2-Br-4-CF3-6-C1 5 -CF3 3-17 2-Cl-6-0nPr-4-CF3 5-CF3 3 -18 4-Br 5-CF3 3-19 3-Br 5-CF3 3-20 2-Br 5-CF3 3-21 2-Br-4-CF3 5-CF3 3-22 3-CF3-4-Br 5 -CF3 3-23 4-1 5-CF3 3-24 3-1 5-CF3 · 3-25 2-1 5-CF3 3-26 2-I-4-CF3 5-CF3 3-27 4-CN 5 -CF3 3-28 3-CN 5-CF3 3-29 2-CN 5-CF3 3-30 2-CN-4-CF3 5-CF3 3-31 4-N02 5-CF3 3-32 3-N02 5- CF3 3-33 2-N02 5-CF3 3-34 2-C1-4-CF3-6-N02 5-CF3 3-35 2-N02-4-CF3 5-CF3 87 1306016 Table 3 (Continued)

Compound No. R 1 R2 Physical commons []: Melting point °C Remarks 3-36 3-CF3-4-N02 5-CF3 3-37 2-CH0-4-CF3 5-CF3 3-38 4_Me 5-CF3 3-39 3-Me 5-CF3 3-40 2-Me 5-CF3 3-41 2, 4-Me2 5-CF3 3-42 2-Me-3-CF3 5-CF3 3-43 2-Me-4-CF3 5 -CF3 3-44 2-Me-4-0CF3 5-CF3 3-45 2-Et-4-CF3 5-CF3 3-46 2, 4, 6-Me3 5-CF3 3-47 2 - Me~*4 - F 5-CF3 3-48 2-Me_4_Cl 5-CF3 3-49 2-Et-4-Cl 5-CF3 3-50 2-nPr-4-Cl 5-CF3 3-51 2-nPr-4-CF3 5-CF3 3-52 2-iPr-4-CF3 5-CF3 3-53 2-CH20Me-4-CF3 5-CF3 3-54 2-CH20Et-4-CF3 5-CF3 3-55 2-CH (0H ) Et-4-CF3 5-CF3 3-56 2-CH20H-4-CF3 5-CF3 3-57 2-CH20CH20Me-4-CF3 5-CF3 3-58 2-CH20CH20Et-4-CF3 5-CF3 3- 59 2-CH20CH(Me)0Me-4-CF3 5-CF3 3-60 2-CH20CH(Me)0Me-4-CF3 5-CF3 3-61 2-CH=CHMe-4-CF3 5-CF3 . 3- 62 2-3 Zhuang 4-0卩3 5-CF3 VB 3-63 4-CF3 5-CF3 [56-58] 3-64 3-CF3 5-CF3 3-65 2-CF3 5-CF3 3-66 3 , 4-(CF3)2 5-CF3 3-67 3, 5-(CF3)2 5-CF3 3-68 2,4-(CF3)2 5-CF3 3-69 2-CH2C1-4-CF3 5- CF3 3-70 2-CH(Cl)Et-4-CF3 5-CF3 3-71 4-CF3 3-C1-5-CF3 3-72 4-CF3 4-Me-6-CF3 88 1306016 Table 3 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °C Remark 3-73 4-OMe 5-CF3 3-74 3-0Me 5-CF3 3-75 2-0Me 5-CF3 3-76 2-〇Me~ 4_CN 5-CF3 3-77 2-0Me-4-CF3 5-CF3 3-78 2-0Et-4-CF3 5-CF3 3-79 2-0Et-4-CF3 5-C1 3-80 2-0Et- 4-CF3 5-Br 3-81 2-0nPr-4-CN 5-CF3 3-82 2-0nPr-4-CF3 5-CF3 [56-58] 3-83 2-0nPr-4-CF3 5-CF3 3-84 2-0nPr-4-CF3 5-CF3 3-85 2-0nPr-4-CF3 5-C1 3-86 2-〇nPr-4-CF3 5-Br 3-87 2-0nPr-4-CF3 5-N02 3-88 2-0nPr-4-CF3 5-NH2 3-89 2-0nPr-4-CF3 5~Me 3-90 2-〇nPr-4-CF3 5-NHS02Me 3-91 2-〇nPr 5-5-CF3 5-CF3 3-92 2-0nPr-4-CF3 6-CF3 3-93 2-0nPr-4-CF3 5-CN 3-94 2-0nPr-4-CF3 5-CF3-6-CN 3-95 2-Cl-6-〇nPr-4-CF3 5-CF3 3-96 2-0iPr-4-CF3 5-CF3 3-97 2-0nBu-4-CF3 5-CF3 3-98 2-〇 iBu-4-CF3 5-CF3 3-99 2-〇nHex-4-CF3 5-CF3 3-100 2-〇nPen-4-CF3 5-CF3 - 3-101 2-0CH2CN-4-CF3 5-CF3 3-102 2-0CH20Me-4-CF3 5-CF3 3-103 2-0CH20Et-4-CF3 5-CF3 3-104 2-0CH20nPr-4-CF3 5-CF3 3-105 2-0CH2cPr-4-CF3 5 -CF3 3-106 2-0CH2cPr-4-CF3 5 -C02Me 3-107 2-0CH2cPr-4-CHF2 5-CF3 3-108 2-0CH2cPr-4-CH0 5-CF3 3-109 2-0CH2cPr-4-CF3 5-CN 3-110 2-0CH2cPr-4- CN 5-CF3 3-111 2-0CH2tBu-4-CF3 5-CF3 89 1306016 Table 3 (Continued)

Compound No. R 1 R2 Physical Constant []: Melting Point °C Remarks 3-112 2-0(CH2)20Me-4-CF3 5-CF3 3-113 2-0(CH2)20Me-4-CF3 5-CN 3- 114 2-0(CH2)20CH20Me-4-CF3 5-CF3 3-115 2-0 (CH2)20H-4-CF3 5-CF3 3-116 2-0CH2Ac-4-CF3 5-CF3 3-117 2- 0CH2CH(0H)Me-4-CF3 5-CF3 3-118 2-0CH2CH(0Me)Me-4-CF3 5-CF3 3-119 2-0CH2C(0H)Me2-4-CF3 5-CF3 3-120 2 -OCH2C(OMe)Me2-4-CF3 5-CF3 3-121 2-OCH2C(Me2)C02Me-4-CF3 5-CF3 3-122 2-0CH2C (0)0Me-4-CF3 5-CF3 3-123 2-0CH2C(0)0Et-4-CF3 5-CF3 3-124 2-0(CH2)20Ac-4-CF3 5-CF3 3-125 2-0(CH2)2NH2-4-CF3 5-CF3 3- 126 2-0(CH2)2NHAc-4-CF3 5-CF3 3-127 2-0(CH2)2NMe2-4-CF3 5-CF3 3-128 2-0CH2CH(Cl)Me-4-CF3 5-CF3 3 -129 2-OCH2CH=CMe2-4-CF3 5-CF3 3-130 2-OCH2CH(Me)OMe-4-CF3 5-CF3 3-131 4-0CF3 5-CF3 92-93 3-132 3-0CF3 5 -CF3 3-133 2-0CF3 5-CF3 3-134 4-0CF2Br 5-CF3 3-135 3-0CF2Br 5-CF3 3-136 2-0CF2Br 5-CF3 3-137 2-0(CH2)2Br-4 -CF3 5-CF3 3-138 2-0(CH2)2Cl-4-CF3 5-CF3 3-139 2-0(CH2)2F-4-CF3 5-CF3 3-140 2-0CH2(Ph-4- Cl)-4-CF3 5-C F3 3-141 2-〇allyl-4-CF3 5-CF3 3-142 2-0allenyl-4-CF3 5-CF3 3-143 2-0propargyl-4-CF3 5-CF3 3-144 2-〇(CH2) 2CH=CH2-4-CF3 5-CF3 3-145 2-0CH2CH=CHMe-4-CF3 5-CF3 3-146 2-0CH2CH=CMe2-4-CF3 5-CF3 3-147 2-0CH2C(Me)= CH2-4-CF3 5-CF3 3-148 2-0CH2CH=CHCl-4-CF3 5-CF3 3-149 2-0Ac-4-CF3 5-CF3 3-150 2-00(0)^-4^3 5-CF3 90 1306016 Table 3 (Continued)

Compound No. R1 R2 Physical constant []: Melting point °C Remarks 3-151 2-0S02Me-4-CF3 5-CF3 3-152 2-0S02Et-4-CF3 5-CF3 3-153 2-S02nPr-4-CF3 5 -CF3 3-154 2-0S02nBu-4-CF3 5-CF3 3-155 2_0S02NMe2_4"CF3 5-CF3 3-156 2-0C(S)NMe2-4-CF3 5-CF3 3-157 2-SC(0) NMe2-4-CF3 5-CF3 3-158 2-NH2-4-CF3 5-CF3 3-159 2-N(nPr)2-4-CF3 5-CF3 3-160 2-NHnPr-4-CF3 5- CF3 3-161 2-N(Me)nPr-4-CF3 5-CF3 3-162 2-NHS02Me-4-CF3 5-CF3 3-163 2-NHS02Et-4-CF3 5-CF3 3-164 2-N (S02nBu)2-4-CF3 5-CF3 3-165 2-SnPr-4-CF3 5-CF3 3-166 2-SCH2cPr-4-CF3 5-CF3 3-167 2-0P(0) (OEt)SnPr -4-CF3 5-CF3

91 1306016

Compound No. R 1 R2 Physical constant "1 : Melting point °C Remark 4-1 4-OH 5-CF3 4-2 3-OH 5-CF3 4-3 2-0H 5-CF3 4 4 2-0H-4-CF3 5-CF3 4 -5 4-F 5-CF3 4 ·€ 3-F 5-CF3 4-7 2-F 5-CF3 4 -8 2-F-4-CF3 5-CF3 4 -9 3-CF3- 4-F 5-CF3 4 -10 4-C1 5-CF3 4-11 3-C1 5-CF3 4 -12 2-C1 5-CF3 4-13 2-C1-4-CF3 5-CF3 4-14 3 -CF3-4-Cl 5-CF3 4-15 2,6-C12-4-CF3 5-CF3 4-16 2-Br-4-CF3-6-Cl 5-CF3 4-17 2-Cl-6- 〇nPr-4-CF3 5-CF3 4-18 4-Br 5-CF3 4 -19 3-Br 5-CF3 4 -20 2-Br 5-CF3 4-21 2-Br-4-CF3 5-CF3 4 -22 3~CF3-4~Br 5-CF3 4-23 4-1 5-CF3 4-24 3-1 5-CF3 4-25 2-1 5-CF3 4-26 2-I-4-CF3 5 -CF3 4-27 4-CN 5-CF3 4-28 3-CN 5-CF3 4-29 2-CN 5-CF3 4-30 2-CN-4-CF3 5-CF3 4-31 4-N02 5- CF3 4-32 3-N02 5-CF3 4-33 2-N02 5-CF3 4-34 2-C1-4-CF3-6-N02 5-CF3 92 1306016 Table 4 (Continued)

Compound No. R 1 R 2 Physical constant f 1 : Melting point °c Remarks 4-35 2-N02-4-CF3 5-CF3 4 -36 3-CF3-4-N02 5-CF3 4 -37 2-CH0-4- CF3 5-CF3 4-38 4-Me 5-CF3 4-39 3-Me 5-CF3 4 40 2-Me 5-CF3 4 -41 2, 4-Me2 5-CF3 4 42 2-Me-3-CF3 5-CF3 4 43 2-Me-4~CF3 5-CF3 4 44 2-Me-4-〇CF3 5-CF3 4 45 2-Et-4-CF3 5-CF3 4 46 2, 4, 6-Me3 5 ,CF3 4 -47 2-Me-4-F 5-CF3 4 48 2-Me-4-Cl 5-CF3 4 -49 2-Et-4-Cl 5-CF3 4 -50 2-nPr-4-Cl 5-CF3 4 -51 2-nPr-4-CF3 5-CF3 4 -52 2-iPr-4-CF3 5-CF3 4 -53 2-CH20Me-4-CF3 5-CF3 4 -54 2-CH20Et-4 -CF3 5-CF3 4 -55 2-CH(OH)Et-4-CF3 5-CF3 4 -56 2-CH20H-4-CF3 5-CF3 4 -57 2-CH20CH20Me-4-CF3 5-CF3 4 - 68 2-CH20CH20Et-4-CF3 5-CF3 4 -59 2-CH20CH(Me)0Me-4-CF3 5-CF3 4 -60 2-CH20CH(Me)0Me-4-CF3 5-CF3 4 -61 2- CH=CHMe-4-CF3 5-CF3 · 4 -62 2-ally1-4-CF3 5-CF3 4 -63 4-CF3 5-CF3 4 -64 3-CF3 5-CF3 4 -€5 2-CF3 5 -CF3 4 -66 3, 4-(CF3)2 5-CF3 4 -67 3, 5-(CF3)2 5-CF3 4 -68 2,4-(CF3)2 5-CF3 4 -69 2-CH2C1 -4-CF3 5-CF 3 4-70 2-CH(Cl)Et-4-CF3 5-CF3 4-71 4-CF3 3-C1-5-CF3 4 -72 4-CF3 4-Me-6-CF3 93 1306016 Table 4 (Continued) table)

Compound No. R 1 R 2 Physical Constant []: Melting Point °C Remarks 4-73 4-OMe 5-CF3 4-74 3-0Me 5-CF3 4 -75 2-OMe 5-CF3 4 -76 2-0Me-4 -CN 5-CF3 4-77 2-0Me-4-CF3 5-CF3 4-78 2-0Et-4-CF3 5-CF3 4-79 2-0Et-4-CF3 5-C1 4 -80 2-〇 Et_4,CF3 5-Br 4 -81 2-〇nPr-4-CN 5-CF3 4 -82 2-0nPr-4-CF3 5-CF3 [55-571 4 -83 2-0nPr-4-CF3 5-CF3 4 -84 2-0nPr-4-CF3 5-CF3 4 -85 2-0"Pr-4-CF3 5-C1 4 -86 2-0nPr-4-CF3 5-Br 4 -87 2-0nPr-4- CF3 5-N02 4-88 2-〇nPr-4-CF3 5-NH2 4 -69 2-〇nPr-4-CF3 5-Me 4 ^90 2-〇nPr-4-CF3 5-NHS02Me 4 -91 2 -〇nPr-5-CF3 5-CF3 4 -92 2-〇nPr-4-CF3 6-CF3 4 -93 2-〇nPr-4-CF3 5-CN 4 -94 2-〇nPr-4-CF3 5 -CF3-6-CN 4 -95 2-Cl-6-〇nPr-4-CF3 5-CF3 4 -96 2-0iPr-4-CF3 5-CF3 4 -97 2-0nBu-4-CF3 5-CF3 4 -98 2-0iBu-4-CF3 5-CF3 4 -99 2-〇nHex-4-CF3 5-CF3· 4-100 2-〇nPen-4-CF3 5-CF3 4-101 2-OCH2CN-4 -CF3 5-CF3 4 -102 2-0CH20Me-4-CF3 5-CF3 4-103 2-0CH20Et-4~CF3 5-CF3 4-104 2-0CH20nPr-4-CF3 5-CF3 4 -105 2-0CH2cPr - 4-CF3 5-CF3 4-106 2-〇CH2cPr-4-CF3 5-C02Me 4-107 2-0CH2cPr-4-CHF2 5-CF3 4-108 2-0CH2cPr-4-CH0 5-CF3 4-109 2 -0CH2cPr-4-CF3 5-CN 4-110 2-0CH2cPr-4-CN 5-CF3 4-111 2-00Η2ιΒυ-4-0Ρ3 5-CF3 94 1306016 Table 4 (Continued)

Compound No. R 1 R2 Physical constant "1 : Melting point °C Remarks 4-112 2-0 (CH2) 20Me-4-CF3 5-CF3 4-113 2-0(CH2)20Me-4-CF3 5-CN 4- 114 2-0(CH2)20CH20Me-4-CF3 5-CF3 4-115 2-0(CH2)20H-4-CF3 5-CF3 4-116 2-0CH2Ac-4-CF3 5-CF3 4-117 2- 0CH2CH(0H)Me-4-CF3 5-CF3 4 -118 2-0CH2CH(0Me)Me-4-CF3 5-CF3 4 -119 2-0CH2C(OH)Me2-4-CF3 5-CF3 4-120 2 -0CH2C(0Me)Me2-4-CF3 5-CF3 4-121 2-OCH2C(Me2)C02Me-4-CF3 5-CF3 4-122 2-0CH2C(0)0Me-4-CF3 5-CF3 4-123 2-0CH2C(0)0Et-4-CF3 5-CF3 4 -124 2-0(CH2)20Ac-4-CF3 5-CF3 4-125 2-0(CH2)2NH2-4-CF3 5-CF3 4 - 126 2-0(CH2)2NHAc-4-CF3 5-CF3 4-127 2-0(CH2)2NMe2-4-CF3 5-CF3 4-128 2-0CH2CH(Cl)Me-4-CF3 5-CF3 4 -129 2-0CH2CH=CMe2-4-CF3 5-CF3 4-130 2-0CH2CH(Me)0Me-4-CF3 5-CF3 4 Ί3 1 4-0CF3 5-CF3 4-132 3-OCF3 5-CF3 4 -133 2-0CF3 5-CF3 4-134 4-0CF2Br 5-CF3 4 *135 3-0CF2Br 5-CF3 4-136 2-0CF2Br 5-CF3 4 -137 2-0(CH2)2Br-4-CF3 5 -CF3 4-138 2-0(CH2)2C1-4-CF3 5-CF3 4-139 2-0(CH2)2F-4-CF3 5-CF3 4-140 2-0CH2(Ph-4-Cl)- 4-CF 3 5-CF3 4-141 2-〇allyl-4-CF3 5-CF3 4-142 2-〇a11eny1-4-CF3 5-CF3 4-143 2-〇propargyl-4-CF3 5-CF3 4-144 2 -0(CH2)2CH=CH2-4-CF3 5-CF3 4-145 2-0CH2CH=CHMe-4-CF3 5-CF3 4-146 2-0CH2CH=CMe2-4-CF3 5-CF3 4-147 2- 0CH2C(Me)=CH2-4-CF3 5-CF3 4-148 2-0CH2CH=CHCl-4-CF3 5-CF3 4-149 2-0Ac-4-CF3 5-CF3 95 1306016

Table 4 (Continued) Compound No. R1 R2 Physical Constant []: Melting Point °C Remarks 4i50 2~OC (6) 5-€F3 4i51 2-0S02Me-4-CF3 5-CF3 4 452 2-0S02Et-4-CF3 5- CF3 4 453 2302^4-03⁄4 5-CF3 4i54 2-0802^1-4-03⁄4 5-CF3 4-155 2-0S02NMe2-4-€F3 5-CF3 4 456 2-<T (5) NMe2-4- CF3 5-CF3 4i57 2-SC (6) NMe2-4-CF3 5-CF3 4 458 2-NH2-4-CF3 5-CF3 4 459 2-^^)2-4-(73 5-CF3 4 460 2-^ ?r-4-<F2 5-CF3 4 461 2-N(Me)nPr-4-€F3 5-CF3 4i62 2-NHS02Me-4-<K3 5-CF3 4 463 2-NHS02Et-4-CF3 5-CF3 4i64 2-_2^11)2-4-〇?3 5-CF3 4 465 2-SnPr-4-CF3 5-CF3 4 466 2-SCH2cPr-4-CF3 5-CF3 4 467 2-0P( 0) (0Et)SnPr-4-CF3 5-CF3

96 1306016 Table 5

Compound No. R1 R2 Physical 薮 []: Melting point 0C Remark 5-1 4-0H 5-CF3 5-2 3-OH 5-CF3 5-3 2-OH 5-CF3 5 4 2-OH-4-CF3 5 -CF3 am or 5 -5 4-F 5-CF3 5 -6 3-F 5-CF3 5-7 2-F 5-CF3 5 -8 2-F-4-CF3 5-CF3 5 -9 3-CF3 -4-F 5-CF3 5-10 4-C1 5-CF3 5-11 3-C1 5-CF3 5 -12 2-C1 5-CF3 5-13 2-C1-4-CF3 5-CF3 5-14 2-C1-4-CF3 5-CF3 5-15 3-CF3-4-C1 5-CF3 5 -16 2, 6-C12-4-CF3 5-CF3 5-17 2-Br-4-CF3-6 -Cl 5-CF3 5-18 2-Cl-6-〇nPr-4-CF3 5-CF3 5 -19 4-Br 5-CF3 5-20 3-Br 5-CF3 5-21 2-Br 5-CF3 5-22 2-Br-4-CF3 5-CF3 [85-87] 5-23 3-CF3-4-Br 5-CF3 5-24 4-1 5-CF3 5 -25 3-1 5-CF3 5 -26 2-1 5-CF3 5-27 2_I_4-CF3 5-CF3 5-28 2-CF3-4-I 5-CF3 5-29 4-CN 5-CF3 5-30 3-CN 5-CF3 5- 31 2-CN 5-CF3 5 -32 2-CN-4-CF3 5-CF3 [125-126] 5-33 2-CF3-4-CN 5-CF3 5-34 4-N02 5-CF3 5-35 3 - N02 5-CF3 97 1306016 Table 5 (Continued)

Compound No. R1 R2 Physical constant "1: Melting point °C Remarks 5-36 2-N02 5-CF3 5-37 2-C1-4-CF3-6-N02 5-CF3 5-38 2-N02-4-CF3 5 -CF3 [107-109] 5-39 3-CF3-4-N02 5-CF3 5 40 2-CHO-4-CF3 5-CF3 5 41 4-Me 5-CF3 5 42 3_Me 5-CF3 5 43 2- Me 5-CF3 5 44 2, 4-Me2 5-CF3 5 45 2-Me-4-CF3 5-CF3 5 46 2-Me-4-0CF3 5-CF3 5 47 2, 4, 6-Me3 5-CF3 5 48 2~Me**4*F 5-CF3 5 -49 2-Me~4~Cl 5-CF3 5 -50 2~Me-4-Br 5-CF3 5 -51 2-Et-4-CF3 5 -CF3 5 -52 2_Me_4-Cl 5-CF3 5 -53 2-Me-4-Br 5-CF3 5 -54 2-Et-4-Cl 5-CF3 5 -55 2-Et-4~CF3 5-CF3 5-56 2-Et-4-0CF3 5-CF3 5 -57 2-nPr-4-Cl 5-CF3 5 -58 2-nPr-4-Br 5-CF3 5 cases 2-nPr-4-CF3 5- CF3 5 -60 2"Pr-4-CF3 5-CF3 5 -61 2-ipr-4-Cl 5-CF3 5 -62 2-1Pr-4-Br 5-CF3 5 -63 2-CH20Me-4-CF3 5-CF3 5 -64 2-CH20Me-4-Cl 5-CF3 5 -65 2-CH20Me-4-Br 5-CF3 5 -66 2-CH20Et-4-CF3 5-CF3 5 -67 2-CH(OH ) Et-4-CF3 5-CF3 5 -68 2-CH20H-4-CF3 5-CF3 5 -69 2-CH20CH20Me-4-CF3 5-CF3 VB 5-70 3-CH20CH20Me-4-CF3 5-CF3 nD 22.5-1.5110 5-71 2-CH20CH20Et-4-CF3 5-CF3 5-72 2-CH20CH(Me)0Me-4-CF3 5-CF3 [56-57] 5-73 2-CH(Me)0CH20Me-4-CF3 5 -CF3 vis 98 1306016 Table 5 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °C Remark 5-74 2-CH=CHMe-4-CF3 5-CF3 5-75 2-ally Bu 4-CF3 5-CF3 am or 5-76 4-CF3 5 -CF3 5-77 3-CF3 5-CF3 5-78 2-CF3 5-CF3 5-79 3, 4-(CF3)2 5-CF3 5 -80 3, 5-(CF3)2 5-CF3 5 - 81 2, 4-(CF3)2 5-CF3 5 -82 2-CH2C1-4-CF3 5-CF3 5 -83 2-CH(Cl)Et-4-CF3 5-CF3 5 -84 4-CF3 3- C1-5-CF3 5 -85 4-CF3 4-Me-6-CF3 5 -86 4~0Me 5-CF3 5 -87 3-0Me 5-CF3 5 -88 2-0Me 5-CF3 5 -89 2- 0Me-4-CF3 5-CF3 VB 5 -90 2-0Et-4-CF3 5-CF3 vis 5 -91 2-0Et-4-CF3 5-C1 5 -92 2-0Et-4-CF3 5-Br 5 -93 2-〇nPr-4-CF3 5-CH2F vis 5 -94 2-〇nPr-4-CF3 5-Me 5 -95 2-0nPr-4-CF3 4-CF3 5 -96 2-〇nPr-4 -CF3 5-CN [95-97] 5 -97 2-〇nPr-4-CF3 5-CF3 [48-50] 5 -98 2-〇nPr-4-CF3 5-CF3 VB N-oxide (Note 4 5 -99 2-〇nPr-4-CF3 5-CHF2 VB 5-100 2-〇nPr-4-CF3 5-CHO [98-100] 5-101 2-〇nPr-4-CF3 5-CH20H VB 5-1022-〇nPr-4-CN 5-CF3 [97-101] 5-103 3-〇nPr-5-CF3 5-CF3 VB 5-104 2-(OcPr-2, 2-C12)-4 -CF3 5-CF3 VB 5-105 2-〇iBu-4-CF3 5-CF3 [74-77] 5 -106 2-0Bn-4-CF3 5-CF3 nD22.3-l.5441 5-107 2-0, -4-.卩3 5-CF3 5-108 2-〇nHex-4-CF3 5-CF3 5 -109 2-〇nPen-4-CF3 5-CF3

99 1306016 Table 5 (Continued)

Compound No. R1 R2 Physical constant f 1 : Melting point 0C Remark 5-110 2-0CH20Me-4-CF3 5-CF3 [86-88] 5-111 2-0CH20Me-4-CF3 5-CN [117-119] 5- 112 2-0CH20Et-4-CF3 5-CF3 5-113 2-0CH20nPr-4-CF3 5-CF3 5-114 2-OCH2CH(Me)0Ac-4-CF3 5-CF3 vis 5-115 2-0CH2C(Me2 )0Ac-4-CF3 5-CF3 vis 5-116 2-〇CH2cPr-4-CF3 5-CF3 [51-53] 5-117 2-0CH2cPr-4-CF3 5-C02Me [136-138] 5-118 2-0CH2cPr-4-CHF2 5-CF3 vis 5-119 2-0CH2cPr-4-CH0 5-CF3 [106-109] 5-120 2-0CH2cPr-4-CF3 5-CN [87-89] 5-121 2-0CH2cPr-4-CN 5-CF3 [109-112] 5-122 2-00Η2ιΒυ-4-ϋΡ3 5-CF3 5-123 2-0(CH2)2OH-4-CF3 5-CF3 vis 5-124 2 -0(CH2)20Me-4-CF3 5-CF3 vis 5-125 2-0(CH2)20Me-4-CF3 5-CN [90-92] 5-126 2-0CH2Ac-4-CF3 5-CF3 vis 5 -127 2-0CH2CH(0H)Me-4-CF3 5-CF3 vis 5-128 2-0CH2CH(0Me)Me-4-CF3 5-CF3 vis 5 -129 2-0CH2C(0H)Me2-4-CF3 5-CF3 vis 5-130 2-0CH2C(0Me)Me2-4-CF3 5-CF3 vis 5 -131 2-OCH2C(Me2)C02Me-4-CF3 5-CF3 vis 5-132 2-0CH2C(0)0Me -4-CF3 5-CF3 vis 5-133 2-0CH2C(0)0Et-4-CF3 5-CF3 vis 5 -134 2-0(CH2)20Ac-4-CF3 5- CF3 vis 5-135 2-0(CH2)2NH2-4-CF3 5-CF3 [61-62] 5-136 2-0(CH2)2NHAc-4-CF3 5-CF3 vis 5-137 2-0(CH2 2NMe2-4-CF3 5-CF3 vis 5-138 2-0CH2CH(Cl)Me-4-CF3 5-CF3 vis 5-139 . 2-0CH2CH=CMe2-4-CF3 5-CF3 vis 5-140 4- OCF3 5-CF3 5-141 3-OCF3 5-CF3 5-142 2-0CF3 5-CF3 5-143 4-0CF2Br 5-CF3 5 -144 3-OCF2Br 5-CF3 5-145 2-〇CF2Br 5-CF3 5-146 2-0(CH2)2Br-4-CF3 5-CF3 5-147 2-0(CH2)2Cl-4-CF3 5-CF3 vis 5-148 2-0(CH2)2F-4-CF3 5 -CF3 100 1306016 Table 5 (Continued)

Compound No. R1 R2 Physical constant "]: Melting point °C Remarks 5-149 2-〇allyl-4-CF3 5-CF3 [47-51] 5-150 2~Oa11eny1-4-CF3 5-CF3 5-151 4- C02Me 5-CF3 5-152 3-C02Me 5-CF3 5 Ί53 2-C02Me 5-CF3 5-154 4-SCF3 5-CF3 5-155 3-SCF3 5-CF3 5-156 2-SCF3 5-CF3 5- 157 4-S(0)CF3 5-CF3 5-158 3-S (9) CF3 5-CF3 5-159 2-S (9) CF3 5-CF3 5-160 4-0S02CF3 5-CF3 5-161 2-0S02Me-4 -CF3 5-CF3 [159-161] 5-162 2-0S02Et-4-CF3 5-CF3 [123-126] 5-163 2-0S02nPr-4-CF3 5-CF3 vis 5-164 2-0S02iPr-4 -CF3 5-CF3 [109-112] 5-165 3-0S02CF3 5-CF3 5-166 2-0S02CF3 5-CF3 5-167 4-OC (6) Ph 5-CF3 5 -168 3-0C(0)Ph 5 -CF3 5-169 2-0C(0)Ph 5-CF3 5-170 4-OCH2Ph 5-CF3 5-171 3-0CH2Ph 5-CF3 5-172 2-0CH2Ph 5-CF3 5-173 4-0CH2(Naph -l-yl) 5-CF3 5-174 2-OCH2C(Me)=CH2-4-CF3 5-CF3 [70-74] 5-175 2-0CH2CH=CHMe-4-CF3 5-CF3 VB Mixture 5 -176 2-〇(CH2)2CH=CH2-4-CF3 5-CF3 vis 5-177 2-0propargy1-4-CF3 5-CF3 vis 5-178 2-(OCH2CH:CC12)-4-CF3 5-CF3 5-179 2, 3, 6-C13-4-0CH2CH=CC12 3-C1- 5-CF3 5-180 2, 3, 6-Cl3-4-0CH2CH=CC12 5-CF3 5-181 2-〇Ac-4-CF3 5-CF3 [157-159] 5-182 2-0CH2C(=N0H )Me-4-CF3(anti) 5-CF3 [120-123] ¢) 5-183 2-OCH2C (=_) Me-4-CF3 (syn) 5-CF3 [55-59] d) 5-184 2-0CH2C(=N0Me)Me-4-CF3(anti) 5-CF3 nD 23.6-1.5100 ¢) 101 1306016 Table 5 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °C Remark 5-185 3-CF3-4-NH2 5-CF3 5-186 2-NH2-4-CF3 5-CF3 [110-113] 5-187 2-NH2 -4-CF3-6-C1 5-CF3 5-188 2-NHMe_4_CF3 5-CF3 5-189 2-NHEt-4-CF3 5-CF3 5-190 2-NHnPr-4-CF3 5-CF3 [65-67 ] 5 Ί91 2-N(Me)nPr-4-CF3 5-CF3 [64-67] 5-192 2-N(nPr)2-4-CF3 5-CF3 5-193 2-NHAc-4-CF3 5 -CF3 [130-132] 5-194 2-N(Ac)nPr-4-CF3 5-CF3 5-195 2-OC(6)0Me-4-CF3 5-CF3 5-196 2-0C(0)SMe-4- CF3 5-CF3 5-197 3-CF3-4-N(S02Me)2 5-CF3 5-198 2-0C(0)Et-4-CF3 5-CF3 [101-105] 5-199 2-OC (6) nPr-4-CF3 5-CF3 [104-106] 5-200 2-_)%-4,3 5-CF3 [127-130] 5-201 2-NHS02Me-4-CF3 5-CF3 [179-182 5-202 2-(0cPr-2,2-C12)-4-CF3 5-CF2H 5-203 2-(1,3-dioxolan-2-ylmethoxy)-4-CF3 5-CF3 VB 5-204 2 - (tetrahydrofuran-2-ylmethoxv)-4-CF3 5-CF3 vis 5-205 2-(tetrahydrofuran-3-ylmethoxy)-4-CF3 5-CF3 [53-55] 5-206 2- (furan-2- Ylmethoxy)-4-CF3 5-CF3 VB 5-207 2-(furan-3-ylmethoxy)-4-CF3 5-CF3 VB 5-208 2-(thiophen-3-vlmethoxv)-4-CF3 5-CF3 VB 5-209 2-(thioph En-2-ylmethoxv)-4-CF3 5-CF3 vis 5-210 2-(OcPr-2, 2-C12)-4-CF3 5-Me 5-211 2- (pyridin-3-ylraethoxy)-4- CF3 5-CF3 nD 22.3-1.5329 5-212 2-(pyridin-2-ylraethoxy)-4-CF3 5-CF3 nD 22.3-1.5335 5-213 2-(oxetan-2-ylmethoxy)-4-CF3 5-CF3 nD 23.2-1.5227 5-214 2-(tetrahydrofuran-2-vloxymethyl)-4-CF3 5-CF3 [78-80] 102 1306016 Table 5 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °C Remarks 5-215 2-(1, 3-dioxolan-2-yl)-4-CF3 5-CF3 [123-126] 5-216 2-CH0-4- CF3 5-CF3 [145-148] 5-217 2-CH20nPr-4-CF3 5-CF3 Πϋ 22.2-1.5158 5-218 2-(4-Me-l, 3-dioxolan-2-yl)-4-CF3 5-CF3 [134-138] 5-219 2-CH20H-4-CF3 5-CF3 [138-141] 5-220 2-CH20Et-4-CF3 5-CF3 [70-741 5-221 2-CH2C1- 4-CF3 5-CF3 [113-116] 5-222 2-CH20CH(0Me)Et-4-CF3 5-CF3 nD 25.0-1.5087 5-223 2-CH20nBu-4-CF3 5-CF3 Nd24.5-l .5123 5-224 2-〇nBu-4-CF3 5-CF3 Nd24.9-l.5145 5-225 2-CH20iPr-4-CF3 5-CF3 [88-91] 5 -226 2-CH20S02Me-4- CF3 5-CF3 Nd24.9-1.5265 5-227 2-CH(0H)nPr-4-CF3 5-CF3 Nd24.9-l.5188 5 -228 2-CH(0Me)nPr-4-CF3 5-CF3 Nd24.8-1.5057 5-229 2-CH20CH(Me)0Et-4-CF3 5-CF3 VB 5-230 2-CH20CH(Me)CN-4-CF3 5-CF3 [105-109] 5-231 2- (CH2〇-tetrahydofuran-3~ vl)-4-CF3 5-CF3 [90-94] 5-232 Tri-CMe-4-CF3 5-CF3 Nd22.3-l.5241 5-233 2-C02Et-4- CF3 5-CF3 [89-91] 5-234 2-0S02CF3-4-CF3 5-CF3 [96-98] 5-235 2-(2, 3-dihydrofuran~2-yl)-4-CF3 5-CF3 [109-111] 5-2 36 2-(2,5-dihydrofuran-2-yl)-4-CF3 5-CF3 [110-112] 5-237 2-(tetrahydrofuran-2-yl)-4~ CF3 5-CF3 [124-126] 5-238 2-CH(0H)nBu-4-CF3 5-CF3 [101-105] 5-239 2-CH(0H)iBu-4-CF3 5-CF3 [50-53] 5-240 2-C (0) nPr-4-CF3 5-CF3 [122-125] 5-241 2-(4, 5-dihydrofuran-3-yl-4-vl)-4-CF3 5-CF3 [126-128] 5- 242 2-CH20CH(Me)Et-4-CF3 5-CF3 Nd23.2-l.5105 5-243 2-C02Me-4-CF3 5-CF3 Nd22.3-1.5229 5 -244 2-C02nPr-4-CF3 5-CF3 [70-75] 5 -245 2-C02iPr-4-CF3 5-CF3 [113-116] 5-246 2-CH2CH20Me-4-CF3 5-CF3 vis 5-247 2-CH=CH0Me-4 -CF3 5-CF3 VB 103 1306016 Table 5 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °C Remarks 5 -248 2-C02H-4-CF3 5-CF3 CL51-155] 5-249 2-C (9)·)Et-4-CF3 5-CF3 128-131 5-250 2-OONH2-4-CF3 5-OR3 Q7&-183] 5-251 2-(X〇)NHEt-4~CF3 5-CF3 Q95-198] 5-252 2-(24ie^l, 3-dioxolan-2-yl)-4-CF3 5-CF3 Q62-164] 5-253 2-C (6) N(f) iPr4-CF3 5-CF3 Q48-150] 5-254 2-C(0)NHiPr-4- CF3 5-CF3 &96-199] 5-255 2-CH(0H)CH2tBu-4-CF3 5-CF3 Q43-145] 5-256 2 — (3~Me~l,2,4-〇xadiazol— 5~ yl)-4-CF3 5-CF3 &36-138] 5-257 2~002tBu-4-CF3 5-CF3 Q59-162] 5-258 2-CH(0Ac)CH2iPr-4-CF3 5- CF3 Nd22.7-1.4952 5-259 2- (4-Me-oxazol izin.-2-^y 1) -4-CF3 5-CF3 Q22-126] 5-260 2- (5-Me-oxazol izin- 2-rl) -4-CF3 &-CF3 197-99] 5-261 2- (4-Me^oxazol-2~vl) -4-CF3 5-CF3 [126-129] 5-262 2-( 4,4-Me2-x»xazolizin-2-vl)-4-CF3 5-CF3 C141-143] 5-263 2-(4-Et-〇xazolizin-2-yl)-4-CF3 5-CF3 110&amp ;-109] 5 -264 4-CF3 5-CF3 [112-115] 5-265 5-〇CH2CN-4-<E3 5-CF3 [80-83]

104 1306016 Table 6

R2 Compound No. R 1 R 2 Physical constant "1: Melting point °C 6-1 4-0H 5-CF3 6-2 3-0H 5-CF3 6-3 2-0H 5-CF3 6-4 2-0H-4 -CF3 5-CF3 am or 6-5 4-F 5-CF3 6 -6 3-F 5-CF3 6-7 2-F 5-CF3 6-8 2-F-4-CF3 5-CF3 6 " 9 3~CF3~4~F 5-CF3 6-10 4-Cl 5-CF3 6 -11 3-C1 5-CF3 6 -12 2-C1 5-CF3 6 -13 2-C1-4-CF3 5- CF3 6-14 3-CF3-4-C1 5-CF3 6-15 2,6-C12-4-CF3 5-CF3 6-16 2-Br-4-CF3-6-Cl 5-CF3 6-17 2 -Cl-6-〇nPr-4-CF3 5-CF3 6-18 4-Br 5-CF3 · 6-19 3-Br 5-CF3 6-20 2-Br 5-CF3 6-21 2-Br-4 -CF3 5-CF3 6-22 3-CF3-4-Br 5-CF3 6-23 4-1 5-CF3 6-24 3-1 5-CF3 6-25 2-1 5-CF3 6-26 2- I-4-CF3 5-CF3 6-27 4-CN 5-CF3 6-28 3-CN 5-CF3 6-29 2-CN 5-CF3 6-30 2-CN-4-CF3 5-CF3 6- 31 4-N02 5-CF3 6-32 3-N02 5-CF3 6-33 2-N02 5-CF3 105 1306016 Table 6 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °C 6-34 2-C1-4-CF3-6-N02 5-CF3 6-35 2-N02-4-CF3 5-CF3 6-36 3-CF3 -4-N02 5-CF3 6-37 2-CH0-4-CF3 5-CF3 6-38 4_Me 5-CF3 6-39 3-Me 5-CF3 6 -40 2-Me 5-CF3 6-41 2, 4-Me2 5-CF3 6-42 2-Me-3-CF3 5-CF3 6 -43 2-Me-4"CF3 5-CF3 6-44 2-Me-4-0CF3 5-CF3 6 -45 2- Et-4-CF3 5-CF3 6-46 2, 4, 6-Me3 5-CF3 6-47 2~Me-4~F 5-CF3 6-48 2-Me~4"C1 5-CF3 6-49 2-Et-4-Cl 5-CF3 6-50 2-nPr-4-Cl 5-CF3 6-51 2-nPr-4-CF3 5-CF3 6-52 2-iPr-4-CF3 5-CF3 6 -53 2-CH20Me-4-CF3 5-CF3 6-54 2-CH20Et-4-CF3 5-CF3 6-55 2-CH(0H)Et-4-CF3 5-CF3 '6-56 2-CH20H- 4-CF3 5-CF3 6-57 2-CH20CH20Me-4-CF3 5-CF3 6-58 2-CH20CH20Et-4-CF3 5-CF3 6-59 2-CH20CH(Me)0Me-4-CF3 5.-CF3 6-60 2-CH20CH(Me)0Me-4-CF3 5-CF3 6-61 2-CH=CHMe-4-CF3 5-CF3 6-62 2-allyl-4-CF3 5-CF3 6-63 4- CF3 5-CF3 6 -64 3-CF3 5-CF3 6-65 2-CF3 5-CF3 6-66 3, 4-(CF3)2 5-CF3 6-67 3, 5-(CF3)2 5-CF3 6-68 2, 4-(CF3)2 5-CF3 6-69 2-CH2C1-4-CF3 5-CF3 6-70 2-CH(Cl)Et-4-CF3 5-CF 3

106 1306016 Table 6 (Continued)

Compound No. R 1 R 2 Physical constant "1: Melting point °c 6-71 4-CF3 3-C1-5-CF3 6-72 4-CF3 4-Me-6-CF3 6-73 4-〇Me 5-CF3 6-74 3-OMe 5-CF3 6 -75 2-0Me 5-CF3 6-76 2-0Me-4-CN 5-CF3 6-7 7 2-0Me-4-CF3 5-CF3 6-78 2- 0Et-4-CF3 5-CF3 6-79 2-0Et-4-CF3 5-C1 6-80 2-0Et-4-CF3 5-Br 6 -81 2-0nPr-4-CN 5-CF3 6-82 2-0nPr-4-CF3 5-CF3 vis 6-83 2-〇nPr-4-CF3 5-CF3 6-84 2-〇nPr-4-CF3 5-CF3 6-85 2-〇nPr-4-CF3 5-C1 6-86 2-〇nPr-4-CF3 5-Br 6-87 2-0nPr-4-CF3 5-N02 6-88 2-0"Pr-4-CF3 5-NH2 6 -89 2- 0nPr-4-CF3 5-Me 6-90 2-0nPr-4-CF3 5-NHS02Me 6-91 2-0nPr-5-CF3 5-CF3 6 -92 2-0nPr-4-CF3 6-CF3 6 -93 2-〇nPr-4-CF3 5-CN 6-94 2-〇nPr-4-CF3 5-CF3-6-CN' 6-95 2-Cl-6-0nPr-4-CF3 5-CF3 6-96 2-〇iPr-4-CF3 5-CF3 6 -97 2-0nBu-4-CF3 5-CF3 6-98 2-0iBu-4-CF3 5-CF3 6-99 2-0nHex-4-CF3 5-CF3 6-100 2-0"Pen-4-CF3 5-CF3 6-101 , 2-OCH2CN-4-CF3 5-CF3 6 -102 2-0CH20Me-4-CF3 5-CF3 [70-74] 6-103 2-0CH20E Bu 4-CF3 5-CF3 6 -104 2-0CH20nPr-4-CF3 5-CF3 6-105 2-0CH2cPr- 4-CF3 5 - CF3 6-106 2-0CH2cPr-4-CF3 5-C02Me 6 -107 2-OCH2cPr-4-CHF2 5-CF3 6 -108 2-0CH2cPr-4-CH0 5-CF3 6-109 2- 0CH2cPr-4-CF3 5-CN 6-110 2-0CH2cPr-4-CN 5-CF3 6-111 2-00Η2ιΒυ-4-0Ρ3 5-CF3 107 1306016 Table 6 (Continued)

Compound No. R 1 R 2 Physical Constant "]: Melting Point °C 6-112 2-0(CH2)20Me-4-CF3 5-CF3 6-113 2-0(CH2)20Me-4-CF3 5-CN 6- 114 2-〇(CH2)20CH20Me-4-CF3 5-CF3 6-115 2-0(CH2)20H-4-CF3 5-CF3 6-116 2-0CH2Ac-4-CF3 5-CF3 6-117 2- 0CH2CH(0H)Me-4-CF3 5-CF3 6-118 2-0CH2CH(0Me)Me-4-CF3 5-CF3 6-119 2-0CH2C(0H)Me2-4-CF3 5-CF3 6-120 2 -0CH2C(0Me)Me2-4-CF3 5-CF3 6-121 2-OCH2C(Me2)C02Me-4-CF3 5-CF3 6-122 2-0CH2C(0)0Me-4-CF3 5-CF3 6-123 2-0CH2C(0)0Et-4-CF3 5-CF3 6-124 2-0(CH2)20Ac-4-CF3 5-CF3 6-125 2-0(CH2)2NH2-4-CF3 5-CF3 6- 126 2-0(CH2)2NHAc-4-CF3 5-CF3 6-127 2-〇(CH2)2NMe2-4-CF3 5-CF3 6-128 2-0CH2CH(Cl)Me-4-CF3 5-CF3 6 -129 2-0CH2CH=CMe2-4-CF3 5-CF3 6-130 2-0CH2CH(Me)0Me-4-CF3 5-CF3 6-131 4-0CF3 5-CF3 6-132 3-0CF3 5-CF3 6 -133 2-0CF3 5-CF3 '6-134 4-0CF2Br 5-CF3 6-135 3-0CF2Br 5-CF3 6-136 2-0CF2Br 5-CF3 6-137 2-0(CH2)2Br-4-CF3 5-.CF3 6-138 2-0(CH2)2Cl-4-CF3 5-CF3 6-139 2-0(CH2)2F-4-CF3 5-CF3 6-140 2-OCH2(Ph-4-Cl )-4-CF3 5-CF3 6-141 2-〇ally Bu 4-CF3 5- CF3 6-142 2-0allenyl-4-CF3 5-CF3 6-143 2-〇propargyl-4-CF3 5-CF3 6-144 2-0 (CH2)2CH=CH2-4-CF3 5-CF3 6 -145 2-0CH2CH=CHMe-4-CF3 5-CF3 6-146 2-0CH2CH=CMe2-4-CF3 5-CF3 6-147 2-0CH2C(Me)=CH2-4-CF3 5-CF3 6-148 2- 0CH2CH=CHCl-4-CF3 5-CF3 108 1306016

Table 6 (Continued) Compound No. · R1 R2 Physical Constant []: Melting Point °C 6-149 2-0Ac-4-CF3 5-CF3 6-150 2-00(0)^-4^3 5-CF3 6 -151 2-〇S02Me-4-CF3 5-CF3 6-152 2-0S02Et-4-CF3 5-CF3 6-153 2-S02nPr-4-CF3 5-CF3 6-154 2-0S02nBu-4-CF3 5 -CF3 6-155 2-0S02NMe2-4-CF3 5-CF3 6-156 2-0C(S)NMe2-4-CF3 5-CF3 6-157 2-SC(0)NMe2-4-CF3 5-CF3 6 -158 2-NH2-4-CF3 5-CF3 6-159 2-N(nPr)2-4-CF3 5-CF3 6-160 2-NHnPr-4-CF3 5-CF3 6-161 2-N(Me nPr-4-CF3 5-CF3 6-162 2-NHS02Me-4-CF3 5-CF3 6-163 2-NHS02Et-4-CF3 5-CF3 6-164 2-N(S02nBu) 2-4-CF3 5 -CF3 6-165 2-SnPr-4-CF3 5-CF3 6 -166 2-SCH2cPr-4-CF3 5-CF3 6-167 2-0P(0) (OEt) SnPr-4-CF3 5-CF3

109 1306016 Table 7

R2 Compound number R 1 R 2 Physical constant []: Melting point °C 7-1 4-0H 5-CF3 7-2 3-0H 5-CF3 7-3 2-0H 5-CF3 7-4 2-OH-4 -CF3 5-CF3 [108-110] 7-5 4-F 5-CF3 7 -6 3-F 5-CF3 7-7 2-F 5-CF3 7-8 2-F-4-CF3 5-CF3 7 -9 3-CF3-4-F 5-CF3 7-10 4-C1 5-CF3 7-11 3-C1 5-CF3 7-12 2-C1 5-CF3 7-13 2-C1-4-CF3 5-CF3 7 -14 3-CF3-4-C1 5-CF3 7-15 2, 6-C12-4-CF3 5-CF3 7-16 2-Br-4-CF3-6-Cl 5-CF3 7- 17 2-Cl-6-〇nPr-4-CF3 5-CF3 7-18 4-Br 5-CF3 7-19 3-Br 5-CF3 7-20 2-Br 5-CF3 7-21 2-Br- 4-CF3 5-CF3 7-22 3-CF3-4-Br 5-CF3 7-23 4-1 5-CF3 7-24 3-1 5-CF3 7-25 2-1 5-CF3 7-26 2 -I-4-CF3 5-CF3 7-27 4-CN 5-CF3 7-28 3-CN 5-CF3 7-29 2-CN 5-CF3 7-30 2-CN-4-CF3 5-CF3 7 -31 4-N02 5-CF3 7-32 3-N02 5-CF3 7-33 2-N02 5-CF3 110 1306016 Table 7 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °C 7-34 2-C1-4-CF3-6-N02 5-CF3 7-35 2-N02-4-CF3 5-CF3 7-36 3-CF3 -4-N02 5-CF3 7-37 2-CHO-4-CF3 5-CF3 7-39 3-Me 5-CF3 7 40 2-Me 5-CF3 7-41 2, 4-Me2 5-CF3 7 A2 2-Me-3-CF3 5-CF3 7-43 2-Me_4-CF3 5-CF3 7-44 2-Me-4-0CF3 5-CF3 7-45 2-Et-4-CF3 5-CF3 7 46 2 , 4, 6-Me3 5-CF3 7-47 2-Me-4-F 5-CF3 7-48 2-Me-4-Cl 5-CF3 7-49 2-Et-4-Cl 5-CF3 7- 50 2-nPr-4-Cl 5-CF3 7 -51 2-nPr-4-CF3 5-CF3 7 -52 2-iPr-4-CF3 5-CF3 7-53 2-CH20Me-4-CF3 5-CF3 7 -54 2-CH20Et-4-CF3 5-CF3 7 -55 2-CH(0H)Et-4-CF3 5-CF3 7 -56 2-CH20H-4-CF3 5-CF3 ' 7-57 2-CH20CH20Me -4-CF3 5-CF3 7 -58 2-CH20CH20Et-4-CF3 5-CF3 7 -59 2-CH20CH(Me)0Me-4-CF3 5-CF3 7 -60 2-CH20CH(Me)0Me-4- CF3 5-CF3 7 -61 2-CH=CHMe-4-CF3 5-CF3 7 -62 2-allyl-4-CF3 5-CF3 7 -63 4-CF3 5-CF3 7 -64 3-CF3 5-CF3 7 -65 2-CF3 5-CF3 7 - €6 3,4-(CF3)2 5-CF3 7 -67 3, 5-(CF3)2 5-CF3 7 -68 2, 4-(CF3)2 5 -CF3 7 -69 2-CH2C1-4-CF3 5-CF3 7 -70 2-CH(Cl)Et-4-CF3 5-CF3

111 1306016 Table 7 (Continued)

Compound No. R 1 R 2 Physical constant f 1 : melting point. C 7-71 4-CF3 3-C1-5-CF3 7-72 4-CF3 4-Me-6-CF3 7-73 4-OMe 5-CF3 7-74 3-0Me 5-CF3 7-75 2~ 0Me 5-CF3 7-76 2~0Me-4_CN 5-CF3 7-77 2-〇Me-4-CF3 5-CF3 7-78 2-0Et-4-CF3 5-CF3 7-79 2-0Et-4 -CF3 5-C1 7-80 2-0Et-4-CF3 5-Br 7-81 2-0nPr-4-CN 5-CF3 7-82 2-0nPr-4-CF3 5-CF3 vis 7-83 2- 〇nPr-4-CF3 5-C1 7-84 2-〇nPr-4-CF3 5-Br 7-85 2-〇nPr-4-CF3 5-N02 7-86 2-〇nPr-4-CF3 5- NH2 7-87 2-0nPr-4-CF3 5-Me 7-88 2-〇nPr-4-CF3 5-NHS02Me 7-89 2-〇nPr-5-CF3 5-CF3 7 -90 2-〇nPr- 4-CF3 6-CF3 7 -91 2-0nPr-4-CF3 5-CN 7 -92 2-0nPr-4-CF3 5-CF3-6-CN 7 -93 2-Cl-6-〇nPr-4- CF3 5-CF3 _ 7-94 2-〇iPr-4-CF3 5-CF3 7 -95 2-0nBu-4-CF3 5-CF3 7 -96 2~0iBu_4"CF3 5-CF3 7 -97 2-0nHex- 4-CF3 5-CF3 7 -98 2-〇nPen-4-CF3 5-CF3 7 -99 2-OCH2CN-4-CF3 5-CF3 7-100 2-0CH20Me-4-CF3 5-CF3 vis 7-101 2-0CH20Et-4-CF3 5-CF3 7-102 2-0CH20nPr-4-CF3 5-CF3 7-103 2-OCH2cPr-4-CF3 5-CF3 vis 7-104 2-0CH2cPr-4-CF3 5-C02Me 7-105 2-0CH2cPr-4-CHF2 5-CF3 7-106 2-0CH2cPr-4-CH0 5-CF3 7- 107 2-0CH2cPr-4-CF3 5-CN 7-108 2-0CH2°Pr-4-CN 5-CF3 7-109 2-0CH2tBu-4-CF3 5-CF3 1306016 Table 7 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °C 7-110 2-0(CH2)20Me-4-CF3 5-CF3 7-111 2-0(CH2)20Me-4-CF3 5-CN 7- 112 2-0 (CH2)20CH20Me-4-CF3 5-CF3 7-113 2-0(CH2)20H-4-CF3 5-CF3 7-114 2-0CH2Ac-4-CF3 5-CF3 7-115 2- 0CH2CH(0H)Me-4-CF3 5-CF3 7-116 2-0CH2CH(0Me)Me-4-CF3 5-CF3 7-117 2-0CH2C(0H)Me2-4-CF3 5-CF3 7-118 2 -0CH2C(OMe)Me2-4-CF3 5-CF3 7-119 2-0CH2C (Me2)C02Me-4-CF3 5-CF3 7-120 2-0CH2C(0)0Me-4-CF3 5-CF3 7 -121 2-0CH2C(0)0Et-4-CF3 5-CF3 7-122 2-0(CH2)20Ac-4-CF3 5-CF3 7-123 2-0(CH2)2NH2-4-CF3 5-CF3 7- 124 2-0(CH2)2NHAc-4-CF3 5-CF3 7-125 2-0(CH2)2NMe2-4-CF3 5-CF3 7-126 2-0CH2CH(Cl)Me-4-CF3 5-CF3 7 -127 2-0CH2CH=CMe2-4-CF3 5-CF3 7-128 2-0CH2CH(Me)OMe-4-CF3 5-CF3 7-129 4-0CF3 5-CF3 7-130 3-0CF3 5-CF3 7 -131 2-0CF3 5-CF3 7-132 4-0CF2Br 5-CF3 7-133 3-0CF2Br 5-CF3 7-134 2-0CF2Br 5-CF3 7-135 2-0(CH2)2Br-4-CF3 5 -CF3 7 -136 2-0(CH2)2Cl-4-CF3 5-CF3 7 -137 2-0(CH2)2F-4-CF3 5-CF3 7-138 2-0CH2(Ph-4-Cl)- 4-CF3 5-CF3 7-139 2-〇allyl-4-CF3 5-CF3 7-140 2-〇allenyl-4-CF3 5-CF3 7-141 2-〇propargyl-4~CF3 5-CF3 7 -142 2-0 (CH2)2CH=CH2-4-CF3 5-CF3 7 -143 2-0CH2CH=CHMe-4-CF3 5-CF3 113 1306016 Table 7 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °C 7-144 2-0CH2CH=CMe2-4-CF3 5-CF3 7-145 2-0CH2C(Me)=CH2-4-CF3 5-CF3 7-146 2-0CH2CH=CHCl-4-CF3 5-CF3 7-147 2-0Ac-4-CF3 5-CF3 7 -148 2-0C(0) ^u-^CFS 5-CF3 7-149 2-0S02Me-4 -CF3 5-CF3 7-150 2-0S02Et-4-CF3 5-CF3 7 -151 2-S02nPr-4-CF3 5-CF3 7-152 2-0S02nBu-4-CF3 5-CF3 7-153 2-0S02NMe2 -4-CF3 5-CF3 7 -154 2-0C(S)NMe2-4-CF3 5-CF3 7-155 2-SC(0)NMe2-4-CF3 5-CF3 7-156 2-NH2-4- CF3 5-CF3 7-157 2-N (nPr) 2-4-CF3 5-CF3 7 -158 2-NHnPr-4-CF3 5-CF3 7-159 2-N(Me)nPr-4-CF3 5- CF3 7-160 2-NHS02Me-4-CF3 5-CF3 7 -161 2-NHS02Et-4-CF3 5-CF3 7 -162 2-N(S02nBu)2-4-CF3 5-CF3 ' 7-163 2- SnPr-4-CF3 5-CF3 7-164 2-SCH2°Pr-4-CF3 5-CF3 7-165 2-0P(0) (0Et)SnPr-4-CF3 5-CF3 114 1306016* Table 8

R2 Compound No. R1 R2 Physical constant []: Melting point °c Remark 8-1 4-0Η 5-CF3 8-2 3-0Η 5-CF3 8-3 2-0Η 5-CF3 8-4 2-0H-4- CF3 5-CF3 8-5 4-F 5-CF3 8-6 3-F 5-CF3 8-7 2-F 5-CF3 8-8 2-F-4-CF3 5-CF3 8-9 3-CF3 -4-F 5-CF3 8-10 4-C1 5-CF3 8-11 3-C1 5-CF3 8-12 2-C1 5-CF3 8-13 2-C1-4-CF3 5-CF3 8-14 3-CF3-4-C1 5-CF3 8-15 2,6-C12-4-CF3 5-CF3 8-16 2-Br-4-CF3-6-C1 5-CF3 8-17 2-Cl-6 -0nPr-4-CF3 5-CF3 8-18 4-Br 5-CF3 8-19 3-Br 5-CF3 8-20 2-Br 5-CF3 8-21 2-Br-4-CF3 5-CF3 8 -22 3-CF3-4-Br 5-CF3 8-23 4-1 5-CF3 8-24 3-1 5-CF3 8-25 2-1 5-CF3 8-26 2-I-4-CF3 5 -CF3 8-27 4-CN 5-CF3 8-28 3-CN 5-CF3 8-29 2-CN 5-CF3 8-30 2-CN-4-CF3 5-CF3 8-31 4-N02 5- CF3 8-32 3-N02 5-CF3 8-33 2-N02 5-CF3 115 :ο - 1306016 Table 8 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °C Remark 8-34 2-C1-4-CF3-6-N02 5-CF3 8-35 2-N02-4-CF3 5-CF3 8-36 3-CF3- 4-N02 5-CF3 8-37 2-CH0-4-CF3 5-CF3 8-38 4-Me 5-CF3 8-39 3~Me 5-CF3 8-40 2-Me 5-CF3 8-41 2 , 4-Me2 5-CF3 8-42 2-Me-3-CF3 5-CF3 8-43 2-Me-4-CF3 5-CF3 8-44 2-Me-4-0CF3 5-CF3 8-45 2 -Et-4-CF3 5-CF3 8-46 2, 4, 6-Me3 5-CF3 8-47 2_Me~4~F 5-CF3 8-48 2-Me-4-Cl 5-CF3 8-49 2 -Et-4-Cl 5-CF3 8-50 2-nPr-4-Cl 5-CF3 8-51 2-"Pr-4-CF3 5-CF3 8-52 2-iPr-4-CF3 5-CF3 8-53 2-CH20Me-4-CF3 5-CF3 8-54 2-CH20Et-4-CF3 5-CF3 8-55 2-CH(0H)Et-4-CF3 5-CF3 8-56 2-CH20H- 4-CF3 5-CF3 8-57 2-CH20CH20Me-4-CF3 5-CF3 8-58 2-CH20CH20Et-4-CF3 5-CF3 8-59 2-CH20CH(Me)0Me-4-CF3 5-CF3 8 -60 2-CH20CH(Me)0Me-4-CF3 5-CF3 8-61 2-CH=CHMe-4-CF3 5-CF3 8-62 2-allyl-4-CF3 5-CF3 8-63 4-CF3 5-CF3 [109-112] 8-64 3-CF3 5-CF3 8-65 2-CF3 5-CF3 8-66 3, 4-(CF3)2 5-CF3 8-67 3, 5-(CF3) 2 5-CF3 8-68 2,4-(CF3)2 5-CF3 8-69 2-CH2C1-4-CF 3 5-CF3 8-70 2-CH(Cl)Et-4-CF3 5-CF3

116 1306016 Table 8 (Continued)

Compound No. R1 R2 Physical constant []: Melting point °c Remark 8-71 4-CF3 3-C1-5-CF3 8-72 4-CF3 4 -Me-~6 - CF3 8-73 4-OMe 5-CF3 8 -74 3 - OMe 5-CF3 8-75 2-0Me 5-CF3 8-76 2-〇Me-4**CN 5-CF3 8-77 2-0Me-4-CF3 5-CF3 8-78 2- 0Et-4-CF3 5-CF3 8-79 2-0Et-4-CF3 5-Cl 8-80 2-0Et-4-CF3 5-Br 8-81 2-〇nPr-4-CN 5-CF3 8- 82 2-0nPr-4-CF3 5-CF3 [47-50] 8-83 2-0nPr-4-CF3 5-Cl 8-84 2-0nPr-4-CF3 5-Br 8-85 2-0nPr-4 -CF3 5-N02 8-86 2-0nPr-4-CF3 5-NH2 8-87 2-0"Pr-4-CF3 5~Me 8-88 2-〇nPr-4-CF3 5-NHS02Me 8-89 2-〇nPr-5-CF3 5-CF3 8-90 2-〇nPr-4-CF3 6-CF3 8-91 2-〇nPr-4-CF3 5-CN 8-92 2-0nPr-4-CF3 5 -CF3-6-CN 8-93 2-Cl-6-0nPr-4-CF3 5-CF3 8-94 2-0iPr-4-CF3 5-CF3 8-95 2-〇nBu-4-CF3 5-CF3 8-96 2-〇iBu-4-CF3 5-CF3 8-97 2-0nHex-4-CF3 5-CF3 8-98 2-〇nPen-4-CF3 5 - CF3 8-99 2-0CH2CN-4- CF3 5-CF3 8-100 2-〇CH20Me-4-CF3 5-CF3 8-101 2-0CH20Et-4-CF3 5-CF3 8-102 2-0CH20nPr-4-CF3 5-CF3 8-103 2-0CH2cPr -4-CF3 5-CF3 8-104 2-0CH2cPr -4-CF3 5-C02Me 8-105 2-0CH2cPr-4-CHF2 5-CF3 8-106 2-0CH2cPr-4-CH0 5-CF3 8-107 2-0CH2cPr-4-CF3 5-CN 8-108 2 -0CH2cPr-4-CN 5-CF3 117 1306016 Table 8 (Continued)

Compound No. R1 R2 Physical constant []: Melting point °c Remark 8-109 2-0ΟΗ2ιΒυ-4-0Ρ3 5-CF3 8-110 2-0(CH2)20Me-4-CF3 5-CF3 8-111 2-0 ( CH2)20Me-4-CF3 5-CN 8-112 2-0 (CH2)20CH20Me-4-CF3 5-CF3 8-113 2-0(CH2)20H-4-CF3 5-CF3 8-114 2-0CH2Ac -4-CF3 5-CF3 8-115 2-0CH2CH(0H)Me-4-CF3 5-CF3 8-116 2-0CH2CH(OMe)Me-4-CF3 5-CF3 8-117 2-0CH2C(0H) Me2-4-CF3 5-CF3 8-118 2-〇CH2C(0Me)Me2-4-CF3 5-CF3 8-119 2-0CH2C(Me2)C02Me-4-CF3 5-CF3 8-120 2-0CH2C (9) 0Me-4-CF3 5-CF3 8-121 2-0CH2C (6). Et-4-CF3 5-CF3 8-122 2-0(CH2)20Ac-4-CF3 5-CF3 8-123 2-0(CH2)2NH2-4-CF3 5-CF3 8-124 2-0(CH2 2NHAc-4-CF3 5-CF3 8-125 2-0(CH2)2NMe2-4-CF3 5-CF3 8-126 2-0CH2CH(Cl)Me-4-CF3 5-CF3 8-127 2-〇CH2CH =CMe2-4-CF3 5-CF3 8-128 2-OCH2CH(Me)OMe-4-CF3 5-CF3 8-129 4-0CF3 5-CF3 [35-38] 8-130 3-0CF3 5-CF3 8 -131 2-0CF3 5-CF3 8-132 4-0CF2Br 5-CF3 8Ί33 3-0CF2Br 5-CF3 8Ί34 2-0CF2Br 5-CF3 8-135 2-0(CH2)2Br-4-CF3 5-CF3 8- 136 2-0(CH2)2Cl-4-CF3 5-CF3 8-137 2-0(CH2)2F-4-CF3 5-CF3 8-138 2-0CH2(Ph-4-Cl)-4-CF3 5 -CF3 8-139 2-〇allyl-4-€F3 5-CF3 8Ί40 2-〇allenyl-4-CF3 5-CF3 8-141 2-〇propargyl-4-CF3 5-CF3 8-142 2-0( CH2) 2CH=CH2-4-CF3 5-CF3 1306016 Table 8 (Continued)

Compound No. R1 R2 Physical constant []: Melting point °c Remark 8-143 2-0CH2CH=aftfe-4-CF3 5-CF3 8-144 2-(XH2CH=CMe2-4-CR3 5-CF3 8-145 2-0CH2C (Me)=CH2-4-CF3 5-CF3 8-146 2-0CH2CH=CH:l-4-CF3 5-CF3 8-147 2~0Ac-4-CF3 5-CF3 8-148 2-00 (0 )^-4-(33⁄4 5-CF3 8-149 2-0S02Me-4-CF3 5-CF3 8-150 2-0S02Et-4-CF3 5-CF3 8-151 2-502^4-03⁄4 5-CF3 8 -152 2-0602^1-4~(?3 5-CF3 8-153 2-0S02NMe2-4-CF3 5-CF3 8-154 2-OC (5)·-4-CF3 5-CF3 8-155 2-SC (0)NWe2-4-{F3 5-CF3 8-156 2-NH2-4-CF3 5-CF3 8-157 2-NCPr)2-4-CF3 5-CF3 8-158 2-NtfPr-4-CF3 5-CF3 8-159 2-N(Me)nPr-4-CF3 5-CF3 8-160 2-MB02M^-4-CF3 5-CF3 8-161 2-ME02Et-4-CF3 5-CF3 8-162 2-^8023⁄4) 2-4-CF3 5-CF3 8-163 5-CF3 8-164 2-SCH2cPr-4-CF3 5-<F3 8-165 2-OP (6)(OEtiS^^Cra 5-CF3 119 1306016 Table 9

Compound No. R1 R2 Physical Constant []: Melting Point °c Remark 9-1 4-0H 5-CF3 9-2 3-ΌΗ 5-CF3 9-3 2-OH 5-CF3 9-4 2-0H-4-CF3 5-CF3 9-5 4-F 5-CF3 9~6 3-F 5-CF3 9-7 2-F 5-CF3 9-8 2-F-4-CF3 5-CF3 9-9 3-CF3- 4-F 5-CF3 9-10 4-C1 5-CF3 9-11 3-C1 5-CF3 9-12 2-C1 5-CF3 9-13 2-C1-4-CF3 5-CF3 9-14 3 -C1-4-CF3 5-CF3 9-15 3-CF3-4-C1 5-CF3 9-16 2,6-C12-4-CF3 5-CF3 9-17 2-Br-4-CF3-6- Cl 5-CF3 9-18 2-01-6-0^4^3 5-CF3 9-19 4-Br 5-CF3 9-20 3-Br 5-CF3 9-21 2-Br 5-CF3 9- 22 2-Br-4-CF3 5-CF3 9-23 3"OF3 -4-Br 5-CF3 9-24 4-1 5-CF3 9-25 3-1 5-CF3 9-26 2-1 5- CF3 9-27 2-I-4-CF3 5-CF3 9-28 2-CF3-4-I 5-CF3 9-29 4-CN 5-CF3 9-30 3-CN 5-€F3 9-31 2 -CN 5-CF3 9-32 2-CN-4-CF3 5-CF3 120 1306016 Table 9 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °C Remarks 9-33 2-CF3-4-CN 5-CF3 9-34 4-N02 5-CF3 9-35 3-N02 5-CF3 9-36 2-N02 5-CF3 9-37 2-C1-4-CF3-6-N02 5-CF3 9-38 2-N02-4-CF3 5-CF3 9-39 3-CF3-4-N02 5-CF3 9-40 2 -CHO-4-CF3 5-CF3 9-41 4~Me 5-CF3 9-42 3_Me 5-CF3 9-43 2_Me 5-CF3 9-44 2,4-Me2 5-CF3 9-45 2-Me- 4-CF3 5-CF3 9-46 2-Me-4-0CF3 5-CF3 9-47 2,4, 6-Me3 5-CF3 9-48 2-Me-4-F 5-CF3 9-49 2- Me-4~C1 5-CF3 9-50 2-Me-4_Br 5-CF3 9-51 2-Et-4-CF3 5-CF3 9-52 2-Me-4^C1 5-CF3 9-53 2eMe- 4-Br 5-CF3 9-54 2-Et-4-Cl 5-CF3 9-55 2-Et-4-CF3 5-CF3 9-56 2-Et-4-0CF3 5-CF3 9-57 2- nPr-4-Cl 5-CF3 . 9-58 2-nPr-4-Br 5-CF3 9-59 2-nPr-4-CF3 5-CF3 9-60 2-^1-4^3 5-CF3 9 -61 2-^^4-01 5-CF3 9-62 2~^Γ"4~Βγ 5-CF3 9-63 2-CH20Me-4-CF3 5-CF3 9-64 2-CH20Me-4-Cl 5 -CF3 9-65 2-CH20Me-4-Br 5-CF3 9-66 2-CH20Et-4-CF3 5-CF3 9-67 2-CH(0H)Et-4-CF3 5-CF3 9-68 2- CH20H-4-CF3 5-CF3 9-69 2-CH20CH20Me-4-CF3 5-CF3 121 1306016 Table 9 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °C Remarks 9-70 3-CH20CH20Me-4-CF3 5-CF3 9-71 2-CH20CH20Et-4-CF3 5-CF3 9-72 2-CH20CH(Me)0Me- 4-CF3 5-CF3 9-73 2-CH=CHMe-4-CF3 5-CF3 9-74 2-allyl-4-CF3 5-CF3 9-75 4-CF3 5-CF3 9-76 3-CF3 5 -CF3 9-77 2-CF3 5-CF3 9-78 3, 4-(CF3)2 5-CF3 9-79 3, 5-(CF3)2 5-CF3 9-80 2,4-(CF3)2 5-CF3 9-81 2-CH2C1-4-CF3 5-CF3 9-82 2-CH(Cl)Et-4-CF3 5-CF3 9-83 4-CF3 3-C1-5-CF3 vis 9-84 4-CF3 3-C1-5-CF3 [131-133] (Note 9-1) 9-85 4-CF3 4-Me-6-CF3 9-86 4-OMe 5-CF3 9-87 3-0Me 5 -CF3 9-88 2-0Me 5-CF3 9-89 2-〇Me-4~CF3 5-CF3 9-90 2-0Et-4-CF3 5-CF3 9-91 2-0Et-4-CF3 5- C1 9-92 2-0Et-4-CF3 5-Br 9-93 2-〇nPr-4-CF3 5-CF3 9-94 2~OnPr-4~CF3 5-CF3 vis 9-95 2-〇nPr- 4-CF3 5-CF3 [107-109] (Note 9-2) 9-96 2-〇nPr-4-CF3 5-CF3 [119-121] (Note 9-3) 9-97 2-〇nBu- 4-CF3 5-CF3 · 9-98 2-0^〇-4-€?3 5-CF3 9-99 2-0nHex-4-CF3 5-CF3 9-100 2-0nPen-4-CF3 5-CF3 9-101 2-0CH20Me-4-CF3 5-CF3 9-102 2-0CH20Et-4-CF3 5-C F3 9-103 2-0CH20nPr-4-CF3 5-CF3 9-104 2-0CH2cPr-4-CF3 5-CF3 9-105 2-0CH2cPr-4-CF3 5-C02Me

122 1306016 Table 9 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °c Remark 9-106 2-0CH2cPr-4-CHF2 5-CF3 9-107 2-0CH2cPr-4-CH0 5-CF3 9-108 2-0CH2cPr-4-CF3 5 -CN 9-109 2-0CH2cPr-4-CN 5-CF3 9-110 2-0CH2tBu-4-CF3 5-CF3 9-111 2-0(CH2)20Me-4-CF3 5-CF3 9-112 2- 0(CH2)20Me-4-CF3 5-€N 9-113 2-0(CH2)20CH20Me-4-CF3 5-CF3 9-114 2-0(CH2)20H-4-CF3 5-CF3 9-115 2-0CH2Ac-4-CF3 5-CF3 9-116 2-0CH2CH(0H)Me-4-CF3 5-CF3 9-117 2-0CH2CH(0Me)Me-4-CF3 5-CF3 9-118 2-OCH2C (OH)Me2-4-CF3 5-CF3 9-119 2-0CH2C(0Me)Me2-4-CF3 5-CF3 9-120 2-0CH2C(Me2)C02Me-4-CF3 5-CF3 9-121 2- 0CH2C (9) 0Me-4-CF3 5-CF3 9-122 2-0CH2C (9) 0Et-4-CF3 5-CF3 9-123 2-0(CH2)20Ac-4-CF3 5-CF3 9-124 2-0 (CH2 2NH2-4-CF3 5-CF3 9-125 2-0(CH2)2NHAc-4-CF3 5-CF3 9-126 2-0(CH2)2NMe2-4-CF3 5-CF3 9-127 2-0CH2CH( Cl)Me-4-CF3 5-CF3 9-128 2-0CH2CH=CMe2-4-CF3 5-CF3 9-129 4-0CF3 5-CF3 . 9-130 3-0CF3 5-CF3 9-131 2-0CF3 5-CF3 9-132 4-0CF2Br 5-CF3 9-133 3-0CF2Br 5-CF3 9-134 2-〇CF2Br 5-CF3 9-135 2- (CH2)2Br-4-CF3 5-CF3 9-136 2-0(CH2)2Cl-4-CF3 5-CF3 9-137 2-〇(CH2)2F-4-CF3 5-CF3 9-138 2- 〇allyl-4-CF3 5-CF3 9-139 2-〇alleny1-4-CF3 5-CF3 9-140 4-C02Me 5-CF3 123 1306016 Table 9 (Continued)

Compound No. R1 R2 Physical constant []: Melting point °c Remarks 9-141 3-C02Me 5-CF3 9-142 2-002Me 5-CF3 9-143 4-SCF3 5-CF3 9-144 3-SCF3 5-CF3 9 -145 2-SCF3 5-CF3 9-146 4-S (9) CF3 5-CF3 9-147 3-S (9) CF3 5-CF3 9-148 2-S (9) CF3 5-€F3 9-149 4-0S02CF3 5- CF3 9-150 3-0S02CF3 5-CF3 9-151 2-0S02CF3 5-CF3 9-152 4-0C (9) Ph 5-CF3 9-153 3~OC (6) Ph 5-CF3 9-154 2-OC (9) Ph 5 -CF3 9-155 4-0CH2Ph 5-CF3 9-156 3-〇CH2Ph 5-CF3 ^-157 2-〇CH2Ph 5-CF3 9-158 4-0CH2(Naph-l-yl) 5-CF3 9-159 2-〇propargyl-4-CF3 5-CF3 9-160 2-(0CH2CH=CC12)-4-CF3 5-CF3 9-161 2,3, &^13-4-〇CH2CH=CC12 3-C1- 5-CF3 9-162 2,3, 6-C13-4-0CH2ai=CC12 5-CF3 9-163 2-0Ac-4-CF3 5-CF3 9-164 3-CF3-4-NH2 5-CF3 · 9 -165 2-NH2-4-CF3 5-CF3 9-166 2-NH2-4-CF3-6-C1 5-CF3 9-167 2-NHMe-4-CF3 5-CF3 9-168 2-NHEt-4 -CF3 5-CF3 ^-169 2-^1¥-4-〇?3 5-CF3 9-170 2-N(nPr)2-4-CF3 5-CF3 9-171 2-N(Ac)nPi- 4-CF3 5-CF3 9-172 2-OC (6) 0Me-4-CF3 5-CF3 9-173 2-〇C(0)SMe-4-C F3 5-CF3 9-174 3-CF3-4-N(S02Me)2 5-CF3 9-175 2~<^0)Et-4-CF3 5-CF3 1306016. Table 1 ο

Compound No. R1 R2 Physical constant []: Melting point °c Remarks 10-1 4-0Η 5-CF3 10-2 3-ΟΗ 5-CF3 10-3 2-ΟΗ 5-CF3 10-4 2-OH-4-CF3 5-CF3 10-5 4-F 5-CF3 10-6 3-F 5-CF3 10-7 2-F 5-CF3 10-8 2-F-4-CF3 5-CF3 10-9 3-CF3- 4-F 5-CF3 10-10 4-C1 5-CF3 10-11 3-C1 5-CF3 10-12 2-C1 5-CF3 10-13 2-C1-4-CF3 5-CF3 10-14 3 -C1-4-CF3 5-CF3 10-15 3-CF3-4-C1 5-CF3 10-16 2,6-C12-4-CF3 5-CF3 10-17 2-Br-4-CF3~*6 -Cl 5-CF3 10-18 2-Cl-6-〇nPr-4-CF3 5-CF3 10-19 4-Br 5-CF3 10-20 3-Br 5-CF3 10-21 2-Br 5-CF3 10-22 2-Br-4-CF3 5-CF3 10-23 3-CF3-4-Br 5-CF3 10-24 4-1 5-CF3 10-25 3-1 5-CF3 10-26 2-1 5-CF3 10-27 2-I-4-CF3 5-CF3 10-28 2-CF3-4-I 5-CF3 10-29 4-CN 5-CF3 10-30 3-CN 5-CF3 10-31 2-CN 5-CF3 10-32 2-CN-4-CF3 5-CF3 10-33 2-CF3-4-CN 5-CF3

125 1306016 Table 1 ο (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °c Remark 10-34 4-N02 5-CF3 10-35 3-N02 5-CF3 10-36 2-N02 5-CF3 10-37 2-C1-4-CF3 -6-N02 5-CF3 10-38 2-N02-4-CF3 5-CF3 10-39 3-CF3-4-N02 5-CF3 10-40 2-CHO-4-CF3 5-CF3 10-41 4 -Me 5-CF3 10-42 3-Me 5-CF3 10-43 2-Me 5-CF3 10-44 2, 4~*Me2 5-CF3 10-45 2-Me-4-CF3 5-CF3 10- 46 2-Me-4-0CF3 5-CF3 10-47 2,4,6-Me3 5-CF3 10-48 2_Me-4-F 5-CF3 10-49 2-Me-4-Cl 5-CF3 10- 50 2~Me-4_Br 5-CF3 10-51 2-Et-4-CF3 5-CF3 10-52 2-Me~4-Cl 5-CF3 10-53 2-Me~4_Br 5-CF3 10-54 2 -Et-4-Cl 5-CF3 10^55 2-Et-4-CF3 5-CF3 10-56 2-Et-4-0CF3 5-CF3 10-57 2-nPr-4-Cl 5-CF3 10- 58 2-nPr-4-Br 5-CF3 10-59 2-nPr-4-CF3 5-CF3 10-60 2-iPr-4-CF3 5-CF3 10-61 2-iPr_4-ci 5-CF3 10- 62 2-iPr-4-Br 5-CF3 10-63 2-CH20Me-4-CF3 5-CF3 10-64 2-CH20Me-4-Cl 5-CF3 10-65 2-CH20Me-4-Br 5-CF3 10-66 2-CH20Et-4-CF3 5-CF3 10-67 2-CH(OH)Et-4-CF3 5-CF3

126 1306016 Table 1 ο (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °c Remark 10-68 2-CH20H-4-CF3 5-CF3 10-69 2-CH20CH20Me-4-CF3 5-CF3 10-70 3-CH20CH20Me-4-CF3 5-CF3 10-71 2-CH20CH20Et-4-CF3 5-CF3 10-72 2-CH20CH(Me)0Me-4-CF3 5-CF3 10-73 2-CH=CHMe-4-CF3 5-CF3 10- 74 2-ally卜 4-CF3 5-CF3 10-75 4-CF3 5-CF3 10-76 3-CF3 5-CF3 10-77 2-CF3 5-CF3 10-78 3,4-(CF3)2 5 -CF3 10-79 3,5-(CF3)2 5-CF3 10-80 2,4-(CF3)2 5-CF3 10-81 2-CH2C1-4-CF3 5-CF3 10-82 2-CH( Cl)Et-4-CF3 5-CF3 10 - 83 4-CF3 3-C1-5-CF3 10-84 4-CF3 4-Me-6-CF3 10-85 4~0Me 5-CF3 10-86 3_0Me 5 -CF3 10-87 2-0Me 5-CF3 10-88 2_0Me**4 - CF3 5-CF3 10-89 2-0Et-4-CF3 5-CF3 10-90 2-0Et-4-CF3 5-C1 10 -91 2-0Et-4-CF3 5-Br 10-92 2-0nPr-4-CF3 5-CF3 10-93 2-〇nPr-4-CF3 5-CF3 [72-74] 10-94 2-0nBu -4-CF3 5-CF3 · 10-95 2-〇iBu-4-CF3 5-CF3 10-96 2-0nHex-4-CF3 5-CF3 10-97 2-0nPen-4-CF3 5-CF3 10- 98 2-0CH20Me-4-CF3 5-CF3 10-99 2-0CH20Et-4-CF3 5-CF3 10-100 2-0CH20nPr-4-CF3 5-CF3 10-101 2 -0CH2cPr-4-CF3 5-CF3 10-102 2-0CH2cPr-4-CF3 5-C02Me 10-103 2-0CH2cPr-4-CHF2 5-CF3 10-104 2-0CH2cPr-4-CH0 5-CF3 10- 105 2-0CH2°Pr-4-CF3 5-CN

127 1306016 Table 1 ο (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °c Remark 10-106 2-0CH2cPr-4-CN 5-CF3 10-107 2-00Η2%-4-〇Ρ3 5-CF3 10-108 2-0(CH2) 20Me-4-CF3 5-CF3 10-109 2-0(CH2)20Me-4-CF3 5-CN 10-110 2-0(CH2)20CH20Me-4-CF3 5-CF3 10-111 2-〇(CH2 20H-4-CF3 5-CF3 10-112 2-0CH2Ac-4-CF3 5-CF3 10-113 2-0CH2CH(0H)Me-4-CF3 5-CF3 10-114 2-OCH2CH(OMe)Me- 4-CF3 5-CF3 10-115 2-0CH2C(0H)Me2-4-CF3 5-CF3 10-116 2-0CH2C(0Me)Me2-4-CF3 5-CF3 10-117 2-0CH2C(Me2)C02Me -4-CF3 5-CF3 10-118 2-OCH2C(9)0Me-4-CF3 5-CF3 10-119 2-0CH2C(0)0Et-4-CF3 5-CF3 10-120 2-0(CH2)20Ac-4- CF3 5-CF3 10-121 2-0(CH2)2NH2-4-CF3 5-CF3 10-122 2-0(CH2)2NHAc-4-CF3 5-CF3 10-123 2-0(CH2)2NMe2-4 -CF3 5-CF3 10-124 2-0CH2CH(Cl)Me-4-CF3 5-CF3 10-125 2-0CH2CH=CMe2-4-CF3 5-CF3 10-128 4-0CF3 5-CF3 10-129 3 -0CF3 5-CF3 10-130 2-0CF3 5-CF3 10-131 4-0CF2Br 5-CF3 10-132 3-0CF2Br 5-CF3 10-133 2~0CF2Br 5-CF3 10-134 2-0(CH2) 2Br-4-CF3 5-CF3 10-135 2-0(CH2)2Cl-4-CF3 5-CF3 10-136 2-0(CH2) 2F-4-CF3 5-CF3 10-137 2-〇allyl-4-CF3 5-CF3 10-138 2-0alleny Bu 4-CF3 5-CF3 10-139 4-C02Me 5-CF3 10-140 3-C02Me 5-CF3 10-141 2-C02Me 5-CF3 10-142 4-SCF3 5-CF3 10-143 3-SCF3 5-CF3 10-144 2-SCF3 5-CF3 128 1306016 Table 1 ο (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °c Remark 10-145 4-S (6) CF3 5-CF3 10-146 3-S(0)CF3 5-CF3 10-147 2-S(0)CP3 5-CF3 10-148 4-0S02CF3 5-CF3 10-149 3-0SO2CF3 5-CF3 10-150 2-0S02CF3 5-CF3 10-151 4-0C(0)Ph 5-CF3 10-152 3-0C(0)Ph 5-CF3 10-153 2-0C(O)Ph 5-CF3 10-154 4-〇CH2Ph 5-CF3 10-155 3-OCH2Ph 5-CF3 10-156 2-€CH2Ph 5-CF3 10-157 4- 0CH2(Naph-l^l) 5-CF3 10-158 2-〇propargyl-4-CF3 5-CF3 10-159 2-(0CH2CH=€C12)-4-CF3 10-160 2,3,6-C13 -4-0CH2CH=0C12 3-C1-5-CF3 10-161 2,3,6-C13-4-0CH2aKX:12 5-CF3 10-162 2-〇Ac-4-CF3 5-CF3 10-163 3 -CF3-4-NH2 5-CF3 10-164 5-CF3 10-165 2-m-4-CF3-6-Cl 5-CF3 10-166 2-mfe-4-CF3 5-CF3 10-167 2- NHEt-4-CF3 5-CF3 . 10-168 2-MfPr-4-CF3 5-CF3 10-169 5-CF3 10-170 2-N(Ac)nPr-4-CF3 &<F3 10-171 2-〇C(〇)0Me-4-CF3 5-CF3 10-172 2-<X:(0)SMe-4-CF3 5-CF3 10-173 3-CF3-4-N(S02Me)2 5 -CF3 10-174 2-C(0)Et-4-CF3 5-CF3 129 1306016» Table 1 1

Compound No. R1 R2 Physical constant []: Melting point °c Remarks 11-1 4-0H 5-CF3 11-2 3-0H 5-CF3 11-3 2-OH 5-CF3 11-4 2-0H-4-CF3 5-CF3 11-5 4-F 5-CF3 11-6 3-F 5-CF3 11-7 2-F 5-CF3 11-8 2-F-4-CF3 5-CF3 11-9 3-CF3- 4-F 5-CF3 11-10 4-C1 5-CF3 11-11 3-C1 5-CF3 11-12 2-C1 5-CF3 11-13 2-C1-4-CF3 5-CF3 11-14 3 -C1-4-CF3 5-CF3 11-15 3-CF3-4-C1 5-CF3 11-16 2,6-C12-4-CF3 5-CF3 11-17 2-Br~4-CF3-6" Cl 5-CF3 11-18 2-Cl-6-0nPr-4-CF3 5-CF3 11-19 4 - Br 5-CF3 11-20 3-Br 5-CF3 11-21 2-Br 5-CF3 11- 22 2-Br-4-CF3 5-CF3 . 11-23 3-CF3-4-Br 5-CF3 11-24 4-1 5-CF3 11-25 3-1 5-CF3 11-26 2-1 5 -CF3 11-27 2-I-4-CF3 5-CF3 11-28 2_CF3~4~I 5-CF3 11-29 4-CN 5-CF3 11-30 3-CN 5-CF3 11-31 2-CN 5-CF3 11-32 2-CN-4-CF3 5-CF3 11-33 2-CF3-4-CN 5-CF3 130 1306016 Table 1 l (Continued)

Compound No. _ R1 R2 Physical < Number []: Melting Point °c Remarks 11-34 4-N02 5-CF3 11-35 3-N02 5-CF3 11-36 2-N02 5-CF3 11-37 2-C1- 4-CF3-6-N02 5-CF3 11-38 2-N02-4-CF3 5-CF3 11-39 3-CF3-4-N02 5-CF3 11-40 2-CHO-4-CF3 5-CF3 11 -41 4"Me 5-CF3 11-42 3-Me 5-CF3 11-43 2-Me 5-CF3 11-44 2, 4-Me2 5-CF3 11-45 2-Me-4-CF3 5-CF3 11-46 2-Me-4-0CF3 5-CF3 11-47 2,4,6-Me3 5-CF3 11-48 2-Me-4-F 5-CF3 11-49 2-Me~4~Cl 5 -CF3 11-50 2-Me*_4',Br 5-CF3 11-51 2-Et-4-CF3 5-CF3 11-52 2-Me-4-Cl 5-CF3 11-53 2-Me-4_Br 5-CF3 11-54 2-Et-4-Cl 5-CF3 11-55 2-Et-4-CF3 5-CF3 11-56 2-Et-4-0CF3 5-CF3 11-57 2-nPr-4 -Cl 5-CF3 11-58 2-nPr-4-Br 5-CF3 11-59 2-nPr-4-CF3 5-CF3 . 11-60 2-iPr-4-CF3 5-CF3 11-61 2- ^^4-01 5-CF3 11-62 2-1Pr~4~Br 5-CF3 11-63 2-CH20Me-4-CF3 5-CF3 11-64 2-CH20Me-4-Cl 5-CF3 11-65 2-CH20Me-4-Br 5-CF3 11-66 2-CH20Et-4-CF3 5-CF3 11-67 2-CH(OH)Et-4-CF3 5-CF3 11-68 2-CH20H-4-CF3 5-CF3 11-69 2-CH20CH20Me-4-CF3 5-CF3 11-70 3-CH20CH20Me-4-CF3 5-CF3 131 1306016 Table 11 l (Continued)

Compound No. R1 R2 Physical constant []: Melting point °c Remarks 11-71 2-CH20CH20Et-4-CF3 5-CF3 11-72 2-CH20CH(Me)0Me-4-CF3 5-CF3 11-73 2-CH= CHMe-4-CF3 5-CF3 11-74 2-allyl-4-CF3 5-CF3 11-75 4-CF3 5-CF3 11-76 3-CF3 5-CF3 11-77 2-CF3 5-CF3 11- 78 3, 4-(CF3)2 5-CF3 11-79 3, 5-(CF3)2 5-CF3 11-80 2,4-(CF3)2 5-CF3 11-81 2-CH2C1-4-CF3 5-CF3 11-82 2-CH(Cl)Et-4-CF3 5-CF3 11-83 4-CF3 3-C1-5-CF3 11-84 4-CF3 4~Me~6~CF3 11-85 4 *0Me 5-CF3 11-86 3-0Me 5-CF3 11-87 2-0Me 5-CF3 11-88 2-0Me-4-CF3 5-CF3 11-89 2-0Et-4-CF3 5-CF3 11 -90 2-0Et-4-CF3 5-C1 11-91 2-0Et-4-CF3 5-Br 11-92 2-〇nPr-4-CF3 5-CF3 11-93 2-〇nPr-4-CF3 5-CF3 VB 11-94 2-0nBu-4-CF3 5-CF3 11-95 2-0iBu-4-CF3 5-CF3 11-96 2-〇nHex-4-CF3 5-CF3 11-97 2-〇 nPen-4-CF3 5-CF3 11-98 2-0CH20Me-4-CF3 5-CF3 ' 11-99 2-0CH20Et-4-CF3 5-CF3 11-100 2-0CH20nPr-4-CF3 5-CF3 11- 101 2-0CH2cPr-4-CF3 5-CF3 11-102 2-0CH2cPr-4-CF3 5-C02Me 11-103 2-0CH2cPr-4-CHF2 5-CF3 11-104 2-〇 CH2cPr-4-CH0 5-CF3 11-105 2-0CH2cPr-4-CF3 5-CN 11-106 2-0CH2cPr-4-CN 5-CF3 11-107 2-0CH2tBu-4-CF3 5-CF3 11-108 2-0(CH2)20Me-4-CF3 5-CF3 11-109 2-0(CH2)20Me-4-CF3 5-CN 132 1306016

Table 11 (continued) 1 Compound No. · R1 R2 Physical Constant []: Melting Point °c Remarks 11-110 2-0(CH2)20CH2CM^-4-CF3 5-CF3 11-111 2-0(CH2)2( H-4-CF3 5-CF3 11-112 2-00^0-4-0=3 5-CF3 11-113 2-0CH2CH(0H)Me-4-CF3 5-CF3 11-114 2-〇CH2CH( 0Me)Me-4-CF3 5-CF3 11-115 2-〇CH2C(0H)Me2-4-CF3 5-CF3 11-116 2-0CH2C(CMe)Me2-4-CF3 5-CF3 11-117 2- 0CH2C (Me2) 002Me-4-€F3 5KF3 11-118 2-0CH2C(0)CMe~4-CF3 5-CF3 11-119 2-0CH2C (6){Et-4~CF3 5-<f3 11-120 2 -0(CH2)20Ac-4-CF3 5-CF3 11-121 2-0(CH2)2NH2-4-CF3 5-€F3 11-122 2-0(CH2)2NHAc-4-CF3 5-CF3 11- 123 2-〇(CH2)2NMe2-4-CF3 5-CF3 11-124 2-0CH2CH(Cl)Me-4-CF3 5. 11-125 2-0CH2CH=CMe2-4-CF3 5-CF3 11-128 4 -0CF3 5-CF3 11-129 3-0CF3 5-CF3 11-130 2-0CF3 5-CF3 11-131 4-0CF2Br 5-CF3 11-132 3-0CF2Br 5-CF3 11-133 2-0CF2Br 5-CF3 . 11-134 2-〇(CH2)2Br-4-CF3 5-CF3 11-135 2-0(CH2)2Cl-4-CF3 5-CF3 11-136 2-0(CH2)2F-4-CF3 5 -CF3 11-137 2-0feillyl-4-CF3 5-<T3 11-138 2-Oallenyl-4-CF3 5-CF3 11-139 4-〇0 2Me 5-CF3 11-140 3-002Me 5-CF3 133 1306016 Table 11 l (Continued)

Compound No. R1 R2 Physical constant []: Melting point °c Remarks 11-141 2-C02Me 5-CF3 11-142 4-SCF3 5-CF3 11-143 3-SCF3 5-CF3 11-144 2-SCF3 5-CF3 11 -145 4-S(0)CF3 5-CF3 11-146 3-S(0)CF3 5-CF3 11-147 2-S (9) CF3 5-CF3 11-148 4-OS02CF3 5-CF3 11-149 3- 0S02CF3 5-CF3 11-150 2-0S02CF3 5-CF3 11-151 4-OC (9) Ph 5-CF3 11-152 3-0C (9) Ph 5-CF3 11-153 2-0C (9) Ph 5-CF3 11-154 4 -0CH2Ph 5-CF3 11-155 3-0CH2Ph 5-CF3 11-156 2-0CH2Ph 5-CF3 11-157 4-0CH2(Naph-l-yl) 5-CF3 11-158 2-〇propargyl-4-CF3 5-CF3 11-159 2-(0CH2CH=CC12)-4-CF3 5-CF3 11-160 2,3,6-Cl3-4-0CH2CH=CCl2 3-C1-5-CF3 11-161 2,3, 6-C13-4-〇CH2CH=CC12 5-CF3 11-162 2-0Ac-4-CF3 5-CF3 11-163 3-CF3-4-NH2 5-CF3 11-164 2-NH2-4-CF3 5 -CF3 11-165 2-NH2-4-CF3-6-C1 5-CF3 1 11-166 2~NHMe~4'*CF3 5-CF3 11-167 . 2-NHEt-4-CF3 5-€F3 11 -168 2-^1-4-(^3 5-CF3 11-169 2-N(nPr)2-4-CF3 5-CF3 11-170 2-N(Ac)nPr-4-CF3 5-CF3 11 -171 2-0C (9) 0Me-4-CF3 5-CF3 11-172 2-OC(6)SMe-4-CF3 5-CF3 11-173 3-CF3-4-N(S02Me)2 5-CF3 11-174 2-C (6) Et-4-CF3 5-CF3

134 1306016 Table 1 2

Compound No. R 1 R2 Physical Constant []: °c Remark 12-1 4-0H 5-CF3 12-2 3-0H 5-CF3 12-3 2-0H 5-CF3 12 -4 2-OH-4-CF3 5-CF3 12 -5 4-F 5-CF3 12 -6 3-F 5-CF3 12 -7 2-F 5-CF3 12 -8 2-F-4-CF3 5-CF3 12 -9 3-CF3- 4-F 5-CF3 12-10 4-C1 5-CF3 12-11 3-C1 5-CF3 12-12 2-C1 5-CF3 12 -13 2-C1-4-CF3 5-CF3 12-14 2 -C1-4-CF3 5-CF3 12-15 3-CF3-4-C1 5-CF3 12-16 2, 6-C12-4-CF3 5-CF3 12-17 2-Br-4-CF3-6- Cl 5-CF3 12-18 2-Cl-6-0nPr-4-CF3 5-CF3 12-19 4-Br 5-CF3 12 -20 3-Br 5-CF3 12-21 2-Br 5-CF3 12- 22 2-Br-4-CF3 5-CF3 12-23 3-CF3-4-Br 5-CF3 12-24 4-1 5-CF3 12-25 3-1 5-CF3 12-26 2-1 5- CF3 12-27 2-I-4-CF3 5-CF3 12-28 2-CF3-4-I 5-CF3 12-29 4-CN 5-CF3 12-30 3-CN 5-CF3 12-31 2- CN 5-CF3 12-32 2-CN-4-CF3 5-CF3 12-33 2-CF3-4-CN 5-CF3 135 1306016 Table 12 (Continued)

Compound No. R 1 R2 Yang Li f administration []: melting point °c Remarks 12-34 4-N02 5-CF3 12-35 3-N02 5-CF3 12-36 2-N02 5-CF3 12-37 2-C1- 4-CF3-6-N02 5-CF3 12-38 2-N02-4-CF3 5-CF3 12-39 3-CF3-4-N02 5-CF3 12 40 2-CH0-4-CF3 5-CF3 12 41 4_Me 5-CF3 12 -42 3-Me 5-CF3 12 43 2-Me 5-CF3 12 44 2, 4-Me2 5-CF3 12 45 2-Me-4-CF3 5-CF3 12 46 2-Me-4 -OCF3 5-CF3 12 47 2, 4, 6-Me3 5-CF3 12 48 2-Me-4_F 5-CF3 12 49 2_Me-4_C1 5-CF3 12 -50 2_Me_4~Br 5-CF3 12 -51 2-Et -4-CF3 5-CF3 12乇2 2*Me_4_Cl 5-CF3 12 -53 2~Me_4_Br 5-CF3 12 -54 2-Et-4-Cl 5-CF3 12 -55 2-Et-4-CF3 5- CF3 12 -56 2-Et-4-0CF3 5-CF3 12 -57 2-nPr-4-Cl 5-CF3 12 -58 2-nPr-4-Br 5-CF3 12 -59 2-nPr-4-CF3 5-CF3. 12 -60 2-ipr-4-CF3 5-CF3 12 -61 2"Pr-4-C1 5-CF3 12 -62 2-iPr-4-Br 5-CF3 12 -63 2-CH20Me- 4-CF3 5-CF3 12 -64 2-CH20Me-4-Cl 5-CF3 12 -65 2-CH20Me-4-Br 5-CF3 12 -66 2-CH20Et-4-CF3 5-CF3 12 -67 2- CH(OH)Et-4-CF3 5-CF3 12 -68 2-CH20H-4-CF3 5-CF3 12 -69 2-CH20CH20M e-4-CF3 5-CF3 12-70 3-CH20CH20Me-4-CF3 5-CF3 136 1306016 Table 12 (Continued)

Compound No. R 1 R2 Physical Constant []: Melting Point °c Remark 12-71 2-CH20CH20Et-4-CF3 5-CF3 12-72 2-CH20CH(Me)0Me-4-CF3 5-CF3 12-73 2-CH (Me)0CH20Me-4-CF3 5-CF3 12-74 2-CH=CHMe-4-CF3 5-CF3 12-75 2-ally1-4-CF3 5-CF3 12-76 4-CF3 5-CF3 12- 77 3-CF3 5-CF3 12-78 2-CF3 5-CF3 12-79 3,4-(CF3)2 5-CF3 12 -80 3, 5-(CF3)2 5-CF3 12 -81 2, 4 -(CF3)2 5-CF3 12 -82 2-CH2C1-4-CF3 5-CF3 12 -83 2-CH(Cl)Et-4-CF3 5-CF3 12 -84 4-CF3 3-C1-5- CF3 12 -85 4-CF3 4-Me-6-CF3 12 -86 4_0Me 5-CF3 12 -87 3-0Me 5-CF3 12 -88 2-OMe 5-CF3 12 -89 2-0Me-4-CF3 5 -CF3 12 -90 2-0Et-4-CF3 5-CF3 12 -91 2-0Et-4-CF3 5-C1 12 -92 2-0Et-4-CF3 5-Br 12 -93 2-〇nPr-4 -CF3 5-CH2F 12 -94 2-0nPr-4-CF3 5~Me 12 95 2-〇nPr-4-CF3 5-CF3 [94-96] 12 -96 2-〇nPr-4-CF3 5-CN 12 -97 2-〇nPr-4-CF3 5-CF3· 12 -98 2-〇nPr-4-CF3 5-CHF2 12 -99 2-0nPr-4-CF3 5-CHO 12-100 2-〇nPr- 4-CF3 5-CH20H 12-101 2-0nPr-4-CN 5-CF3 12-102 3-〇nPr-5-CF3 5-CF3 12-103 2-(OcPr-2, 2-C12) -4-CF3 5-CF3 12-104 2-〇iBu-4-CF3 5-CF3 12-105 2-0Bn-4-CF3 5-CF3 12-106 2-〇411-4-.卩3 5-CF3 12-107 2-〇nHex-4-CF3 5-CF3 12-108 2-0nPen-4-CF3 5-CF3

137 1306016 Table 12 (Continued)

Compound No. R1 R2 Physical Constant []: Melting Point °c Remarks 12-109 2-0CH20Me-4-CF3 5-CF3 12-110 2-0CH20Me-4-CF3 5-CN 12-111 2-0CH20Et-4-CF3 5 -CF3 12 -112 2-0CH20nPr-4-CF3 5-CF3 12-113 2-0CH2CH(Me)0Ac-4-CF3 5-CF3 12-114 2-0CH2C(Me2)0Ac-4-CF3 5-CF3 12 -115 2-0CH2cPr-4-CF3 5-CF3 12-116 2-0CH2cPr-4-CF3 5-C02Me 12-117 2-0CH2cPr-4-CHF2 5-CF3 12 -118 2-0CH2cPr-4-CH0 5- CF3 12-119 2-0CH2cPr-4-CF3 5-CN 12-120 2-0CH2cPr-4-CN 5-CF3 12-121 2-0CH2tBu-4-CF3 5-CF3 12-122 2-0(CH2)20H -4-CF3 5-CF3 12-123 2-0(CH2)20Me-4-CF3 5-CF3 12-124 2-0(CH2)20Me-4-CF3 5-CN 12-125 2-0CH2Ac-4- CF3 5-CF3 12-126 2-0CH2CH(0H)Me-4-CF3 5-CF3 12-127 2-OCH2CH(OMe)Me-4-CF3 5-CF3 12-128 2-0CH2C(0H)Me2-4 -CF3 5-CF3 12-129 2-OCH2C(OMe)Me2-4-CF3 5-CF3 12-130 2-0CH2C(Me2)C02Me-4-CF3 5-CF3 12-131 2-0CH2C(6)0Me-4-CF3 5 -CF3 12-132 2-0CH2C(0)0Et-4-CF3 5-CF3 12-133 2-0(CH2)20Ac-4-CF3 5-CF3 12-134 2-0(CH2)2NH2-4-CF3 5-CF3' 12-135 2-0(CH2)2NHAc-4-CF3 5-CF3 12-136 2-0 (CH2)2NMe2-4-CF3 5-CF3 12-137 2-0CH2CH(Cl)Me-4-CF3 5-CF3 12-138 2-0CH2CH=CMe2-4-CF3 5-CF3 12-139 4-0CF3 5 -CF3 12-140 3-0CF3 5-CF3 12-141 2-0CF3 5-CF3 12-142 4-0CF2Br 5-CF3 12-143 3-0CF2Br 5-CF3 12-144 2-0CF2Br 5-CF3 138 1306016

Table 12 (Continued) Compound No. R1 R2 Physical Constant []: Melting Point °c Remarks 12-145 2-0(CH2)2Br-4-GF3 5-CF3 12-146 2-0(CH2)2Cl-4-CF3 &-CF3 12-147 2-〇(CH2)2F-4-CF3 5-€F3 12-148 2-0allyl-4-CF3 5-CF3 12-149 2-〇allenyl-4-CF3 5-CF3 12 -150 4-€Q2Me 5-CF3 12-151 3-C02Me 5-CF3 12-152 2-002Me 5-CF3 12-153 4-SCF3 5-CF3 12-154 3-SCF3 5-CF3 12-155 2- SCF3 5-CF3 12-156 4-S (9) CF3 5-CF3 12-157 3-S(0)CF3 5-CF3 12-158 2-S(0)CF3 5-€F3 12-159 4-0SQ2CF3 5- CF3 12-160 2-OS02M&-4-CF3 5-CF3 12-161 2-0S02Et-4-CF3 5-CF3 12-162 2-0502^4-03⁄4 5-CF3 12-163 2-0602^4- 03⁄4 5-€F3 12-164 3-OSQ2CF3 5-<F3 12-165 2-0S02CF3 5-€F3' 12-166 4-0C(0)Ph 5-CF3 12-167 3-0C(0)Ph 5-CF3 12-168 2-0C(0)Ph 5-CF3 12-169 4-〇CH2Ph 5-CF3 12-170 3-0CH2Ph 5-CF3 139 1 / 1306016 Table 12 (Continued)

Compound No. R1 R2 cleavage constant []: melting point °c Remark 12-171 2-0CH2Ph 5-CF3 12-172 4-0CH2(Naph-l-yl) 5-CF3 12-173 2-0CH2C(Me)=CH2 -4-CF3 5-CF3 12-174 2-0CH2CH=CHMe-4-€F3 5-CF3 12-175 2-0(CH2)2CH=CH2-4-CF3 5-CF3 12-176 2-〇propargyl- 4~€F3 5-CF3 12-177 2-(0CH2CH=CC12)-4-CF3 5-CF3 12-178 2, 3,6-C13-4-0CH2CH=CC12 3-C1-5-CF3 12-179 2, 3,6-C13-4-0CH2CH=CC12 5-CF3 12-180 2~OAc -4~CF3 5-CF3 12-181 2-0CH2C (=N0H) Me-4-CH0(anti) 5-CF3 12-182 2-OCH2C(=NOH)Me-4-CH0(syn) 5-CF3 12-183 2-0CH2C(=N0Me)Me-4~CH0(anti) 5-CF3 12-184 3-CF3-4 -NH2 5-CF3 12-185 2-NH2-4-CF3 5-CF3 12-186 2-NH2-4-CF3-6-C1 5-CF3 12-187 2~NHMe~4"CF3 5-CF3 12- 188 2-NHEt-4-CF3 5-CF3 12-189 2-ΝΗ"Ργ-4-€Ρ3 5-CF3 12-190 2-N(Me)nPr-4-CF3 5-CF3 12-191 2-N (nPr)2-4-€F3 5-CF3 12-192 2-NHAc-4-CF3 5-CF3- 12-193 2-N(Ac)nPr-4-CF3 5-€F3 12-194 2-OC (9) 0Me-4~CF3 5-CF3 12-195 2-OC (9) SMe-4-CF3 5-CF3 12-196 3-CF3-4-N(S02Me)2 5-CF3 12-197 2~OC Et-4-CF3 5-CF3 12-198 2~€C (6) nPH-CF3 5-CF3 12-199 2-OC (9) 5-CF3 12-200 2-NHS02Me-4-CF3 5-CF3 12-201 2- (0cPr-2,2-C12)-4-CF3 5-CF3 140 1306016 Table 1 3

Compound No. R 1 R 2 Physical Constant []: Melting Point °c 13-1 4-OH 5-CF3 13-2 3-0H 5-CF3 13-3 2-OH 5-CF3 13 -4 2-OH-4- CF3 5-CF3 13 -5 4-F 5-CF3 13 -6 3-F 5-CF3 13-7 2-F 5-CF3 13-8 2-F-4-CF3 5-CF3 13 -9 3-CF3 -4-F 5-CF3 13-10 4-C1 5-CF3 13-11 3-C1 5-CF3 13-12 2-C1 5-CF3 13-13 2-C1-4-CF3 5-CF3 13-14 3-CF3-4-C1 5-CF3 13 -15 2, 6-C12-4-CF3 5-CF3 13 *16 2-Br-4-CF3-6-Cl 5-CF3 13 -17 2-Cl-6 -〇nPr-4-CF3 5-CF3 13-18 4-Br 5-CF3 13-19 3-Br 5-CF3 13-20 2-Br 5-CF3 13-21 2-Br-4-CF3 5-CF3 13-22 3-CF3-4-Br 5-CF3 13-23 4-1 5-CF3 13-24 3-1 5-CF3 13-25 2-1 5-CF3 13-26 2-I-4-CF3 5-CF3 13-27 4-CN 5-CF3 13-28 3-CN 5-CF3 13-29 2-CN 5-CF3 13-30 2-CN-4-CF3 5-CF3 13-31 4-N02 5 -CF3 13-32 3-N02 5-CF3 13-33 2-N02 5-CF3 141 1306016 Table 13 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °c 13-34 2-C1-4-CF3-6-N02 5-CF3 13-35 2-N02-4-CF3 5-CF3 13-36 3-CF3 -4-N02 5-CF3 13-37 2-CH0-4-CF3 5-CF3 13-38 3-Me 5-CF3 13-39 2-Me 5-CF3 13-40 2, 4-Me2 5-CF3 13 -41 2-Me-3-CF3 5-CF3 13-42 2-Me-4-CF3 5-CF3 13-43 2_Me_4~0CF3 5-CF3 13-44 2-Et-4-CF3 5-CF3 13-45 2, 4, 6-Me3 5-CF3 13-46 2-Me-4-F 5-CF3 13-47 2_Me~*4-Cl 5-CF3 13-48 2-Et~4-Cl 5-CF3 13- 49 2-nPr-4-Cl 5-CF3 13-50 2-nPr-4-CF3 5-CF3 13-51 2_ipr_4_CF3 5-CF3 13-52 2-CH20Me-4-CF3 5-CF3 13-53 2-CH20Et -4-CF3 5-CF3 13-54 2-CH(0H)Et-4-CF3 5-CF3 13-55 2-CH20H-4-CF3 5-CF3 13-56 2-CH20CH20Me-4-CF3 5-CF3 13-57 2-CH20CH20Et-4-CF3 5-CF3 13-58 2-CH20CH(Me)OMe-4-CF3 5-CF3 13-59 2-CH20CH(Me)0Me-4-CF3 5-CF3 13-60 2-CH=CHMe-4-CF3 5-CF3 13-61 2-allyb 4-CF3 5-CF3 13-62 4-CF3 5-CF3 13-63 3-CF3 5-CF3 13-64 2-CF3 5 -CF3 13-65 3, 4-(CF3)2 5-CF3 13-66 3, 5-(CF3)2 5-CF3 13-67 2, 4-(CF3)2 5-CF3 13-68 2-CH2C1 -4-CF3 5-CF3 13-69 2-CH(Cl)Et-4-CF3 5-CF3 13-70 4-CF3 3-C1-5-CF3 13-71 4-CF3 4-Me-6-CF3 142 1306016 Table 13 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °c 13-72 4-〇Me 5-CF3 13-73 3-0Me 5-CF3 13-74 2-0Me 5-CF3 13-75 2-0Me-4 -CN 5-CF3 13-76 2-0Me-4-CF3 5-CF3 13-77 2-0Et-4-CF3 5-CF3 13-78 2-0Et-4-CF3 5-C1 13-79 2-0Et -4-CF3 5-Br 13-80 2-0nPr-4-CN 5-CF3 13-81 2-〇nPr-4-CF3 5-CF3 Nd22. 2-1. 5140 13-82 2-〇nPr-4 -CF3 5-C1 13-83 2-〇nPr-4-CF3 5-Br 13-84 2-〇nPr-4-CF3 5-N02 13-85 2-〇nPr-4-CF3 5-NH2 13-86 2-0nPr-4-CF3 5-Me 13-87 2-〇nPr-4-CF3 5-NHS02Me 13-88 2-〇nPr-5-CF3 5-CF3 13-89 2-〇nPr-4-CF3 6 -CF3 13 -90 2-〇nPr-4-CF3 5-CN 13 ^91 2-0nPr-4-CF3 5-CF3-6-CN 13 -92 2-Cl-6-〇nPr-4-CF3 5- CF3 13 -53 2-〇iPr-4-CF3 5-CF3 13 -94 2-0nBu-4-CF3 5-CF3 13 -95 2-〇iBu-4-CF3 5-CF3 13 -96 2-0nHex-4 -CF3 5-CF3 13 -97 2-0nPen-4-CF3 5-CF3 13 -98 2-0CH2CN-4-CF3 5-C.F3 13 -99 2-0CH20Me-4-CF3 5-CF3 13-100 2 -0CH20Et-4-CF3 5-CF3 13-101 2-0CH20nPr-4-CF3 5-CF3 13-102 2-0CH2cPr-4-CF3 5-CF3 13-103 2-0CH2cPr-4-CF3 5-C02Me 13- 104 2-0CH2cPr-4-CHF2 5-C F3 13-105 2-0CH2°Pr-4-CH0 5-CF3 13 -106 2-0CH2cPr-4-CF3 5-CN 13-107 2-0CH2cPr-4-CN 5-CF3 13-108 2-00Η2ιΒυ-4 -0Ρ3 5-CF3 13-109 2-0(CH2)20Me-4-CF3 5-CF3 13-110 2-0(CH2)20Me-4-CF3 5-CN 143 1306016 Table 13 (Continued)

• Compound No. R 1 R 2 Physical Constant []: Melting Point °c 13-111 2-0(CH2)20CH20Me-4-CF3 5-CF3 13-112 2-0(CH2)20H-4-CF3 5-CF3 13 -113 2-0CH2Ac-4-CF3 5-CF3 13-114 2-0CH2CH(0H)Me-4-CF3 5-CF3 13-115 2-0CH2CH(0Me)Me-4-CF3 5-CF3 13-116 2 -0CH2C(0H)Me2-4-CF3 5-CF3 13-117 2-0CH2C(0Me)Me2-4-CF3 5-CF3 13-118 2-0CH2C(Me2)C02Me-4-CF3 5-CF3 13-119 2-0CH2C(0)0Me-4-CF3 5-CF3 13-120 2-0CH2C(0)0Et-4-CF3 5-CF3 13-121 2-0(CH2)20Ac-4-CF3 5-CF3 13 - 122 2-0(CH2)2NH2-4-CF3 5-CF3 13-123 2-0(CH2)2NHAc-4-CF3 5-CF3 13-124 2-0(CH2)2NMe2-4-CF3 5-CF3 13 -125 2-0CH2CH(Cl)Me-4-CF3 5-CF3 13-126 2-0CH2CH=CMe2-4-CF3 5-CF3 13-127 2-0CH2CH(Me)0Me-4-CF3 5-CF3 13- 128 4-0CF3 5-CF3 13-129 3-0CF3 5-CF3 13-130 2-0CF3 5-CF3 13 -131 4-0CF2Br 5-CF3 13-132 3-0CF2Br 5-CF3 13-133 2-0CF2Br 5 -CF3 13-134 2-0(CH2)2Br-4-CF3 5-CF3 13-135 2-0(CH2)2Cl-4-CF3 5-CF3 13-136 2-0(CH2)2F-4-CF3 5-CF3 13-137 2-0CH2(Ph-4-Cl)-4-CF3 5-CF3 13-138 2-〇allyl-4-CF3 5-CF3 13-139 2-0allenyl-4-CF3 5-CF3 13-14 0 2-0propargyl-4~CF3 5-CF3 13-141 2-0(CH2)2CH=CH2-4-CF3 5-CF3 13-142 2-0CH2CH=CHMe-4-CF3 5-CF3 13-143 2- 0CH2CH=CMe2-4-CF3 5-CF3 13 *144 2-0CH2C(Me)=CH2-4-CF3 5-CF3 13-145 2-0CH2CH=CHCl-4-CF3 5-CF3 13-146 2-OAc- 4-CF3 5-CF3 144 1306016

Table 13 (Continued) Compound No. Ri R2 Physical Constant []: Melting Point °c 13-147 2-_)士11-4. 5-CF3 13-148 2-〇S02Me-4-CF3 5-CF3 13 -149 2-〇S02Et-4-CF3 5-CF3 13-150 2-S02nPr-4-CF3 5-CF3 13-151 2-0S02nBu-4-CF3 5-€F3 13-152 2-0S02NMe2-4-CF3 5- €F3 13-153 2-OC (5) NMe2-4-CF3 5-CF3 13-154 2-SC(9)NMe2-4-CF3 5-CF3 13-155 2-NH2-4-CF3 5-CF3 13-156 2-N( nPr)2-4-CF3 5-CF3 13 457 2-NHnPr-4-€F3 5-CF3 13-158 2-N(Me)nPr-4-CF3 5-CF3 13-159 2-NHS02Me-4-CF3 5-CF3 13-160 2-NHS02Et-4-CF3 5-€F3 13-161 2-N(S02nBu)2-4-CF3 5-CF3 13-162 2-SnPr-4-CF3 5-CF3 13-163 2-SCH2cPr-4-CF3 5-CF3 13-164 2-0P(0) (0Et)SnPr-4-CF3 5-CF3

145 1306016 Table 1 4

Compound No. R 1 R 2 Physical Constant _ []: Melt Si.°C 14 -1 4-0H 5-CF3 14-2 3-0H 5-CF3 14-3 2-0H 5-CF3 14-4 2-OH -4-CF3 5-CF3 14-5 4-F 5-CF3 14-6 3-F 5-CF3 14-7 2-F 5-CF3 14-8 2-F-4-CF3 5-CF3 14-9 3-CF3-4-F 5-CF3 14-10 4-C1 5-CF3 14-11 3-C1 5-CF3 14-12 2-C1 5-CF3 14-13 2-C1-4-CF3 5-CF3 14-14 3-CF3-4-C1 5-CF3 14-15 2,6-C12-4-CF3 5-CF3 14-16 2-*Br-4-CF3-6-Cl 5-CF3 14-17 2 -Cl-6-0nPr-4-CF3 5-CF3 14-18 4-Br 5-CF3. 14-19 3-Br 5-CF3 14-20 2-Br 5 - CF3 14-21 2-Br-4- CF3 5-CF3 14-22 3-CF3-4-Br 5-CF3 14-23 4-1 5-CF3 14-24 3-1 5-CF3 14-25 2-1 5-CF3 14-26 2-I -4-CF3 5-CF3 14-27 4-CN 5-CF3 14-28 3-CN 5-CF3 14-29 2-CN 5-CF3 14-30 2-CN-4-CF3 5-CF3 14-31 4-N02 5-CF3 14-32 3-N02 5-CF3 14-33 2-N02 5-CF3 146 1306016 Table 1 4 (Continued)

Compound No. R 1 R 2 ... physical tit [ []: melting point °c 14 -34 2-C1-4-CF3-6-N02 5-CF3 14-35 2-N02-4-CF3 5-CF3 14 -36 3- CF3-4-N02 5-CF3 14-37 2-CH0-4-CF3 5-CF3 14-38 4 - Me 5-CF3 14 -39 3-Me 5-CF3 14 -40 2-Me 5-CF3 14 41 2, 4-Me2 5-CF3 14 -42 2-Me-3-CF3 5-CF3 14 -43 2-Me-4-CF3 5-CF3 14 44 2-Me-4-0CF3 5-CF3 14-45 2 -Et-4-CF3 5-CF3 14-46 2, 4, 6-Me3 5-CF3 14 47 2-Me-4_F 5-CF3 14 -48 2-Me_4_Cl 5-CF3 14 49 2-Et-4-Cl 5-CF3 14 -50 2-nPr-4-Cl 5-CF3 14 -51 2-nPr-4-CF3 5-CF3 14 -52 2-ipr-4-CF3 5-CF3 14 -53 2-CH20Me-4 -CF3 5-CF3 · 14 -54 2-CH20Et-4-CF3 5-CF3 14 -55 2-CH(OH)Et-4-CF3 5-CF3 14 -56 2-CH20H-4-CF3 5-CF3 14 -57 2-CH20CH20Me-4-CF3 5-CF3 14 -58 2-CH20CH20Et-4-CF3 5-CF3 14 -59 2-CH20CH(Me)0Me-4-CF3 5-CF3 14 -60 2-CH20CH (Me ) 0Me-4-CF3 5-CF3 14 -61 2-CH=CHMe-4-CF3 5-CF3 14 -62 2-allyl-4-CF3 5-CF3 14 -63 4-CF3 5-CF3 14 -64 3 -CF3 5-CF3 14 -65 2-CF3 5-CF3 14 -66 3, 4-(CF3)2 5-CF3 14 -67 3, 5-(CF3)2 5-CF3 147 1306016 Table 14 (Continued)

Compound No. R 1 R 2 Physical Constant []: Melting Point °c 14 -68 2,4-(CF3)2 5-CF3 14-69 2-CH2C1-4-CF3 5-CF3 14-70 2-CH(Cl) Et-4-CF3 5-CF3 14-71 4-CF3 3-C1-5-CF3 14-72 4-CF3 4-Me_6-CF3 14-73 4-OMe 5-CF3 14 -74 3-0Me 5-CF3 14-75 2-0Me 5-CF3 14-76 2-0Me-4-CN 5-CF3 14-77 2~OMe~4-CF3 5-CF3 14-78 2-0Et-4-CF3 5-CF3 14- 79 2-0Et-4-CF3 5-C1 14-80 2-0Et-4-CF3 5-Br 14-81 2-0nPr-4-CN 5-CF3 14-82 2-0nPr-4-CF3 5-CF3 Vis 14-83 2-0nPr-4-CF3 5-CF3 14 -84 2-0nPr-4-CF3 5-CF3 14 -85 2-〇nPr-4-CF3 5-C1 14 -86 2-〇nPr-4 -CF3 5-Br 14-87 2-〇nPr-4-CF3 5-N02 14-88 2-〇nPr-4-CF3 5-NH2 14-89 2-〇nPr-4-CF3 5_Me 14-90 2- 〇nPr-4-CF3 5-NHS02Me 14-91 2-〇nPr-5-CF3 5-CF3 14-92 2-0nPr-4-CF3 6-CF3 14 -93 2-0nPr-4-CF3 5-CN 14 -94 2-0nPr-4-CF3 5-CF3-6-CN 14-95 2-Cl-6-〇nPr-4-CF3 5-CF3 14 -96 2-〇iPr-4-CF3 5-CF3 14 - 97 2-0nBu-4-CF3 5-CF3 14 -98 2-〇iBu-4-CF3 5-CF3 14 -99 2-0nHex-4-CF3 5-CF3 14-100 2-〇nPen-4-CF3 5 -CF3 14-101 2-0CH2CN-4-CF3 5-CF3 14-102 2-0C H20Me-4-CF3 5-CF3 14-103 2-0CH20Et-4-CF3 5-CF3 14-104 2-0CH20nPr-4-CF3 5-CF3 148 1306016 Table 14 (Continued)

Compound No. R 1 R 2 ·- 瑝 瑝 []: melting point °c 14-105 2-0CH2cPr-4-CF3 5-CF3 14-106 2-0CH2cPr-4-CF3 5-C02Me 14-107 2-0CH2cPr- 4-CHF2 5-CF3 14-108 2-0CH2cPr-4-CH0 5-CF3 14-109 2-0CH2cPr-4-CF3 5-CN 14-110 2-0CH2cPr-4-CN 5-CF3 14-111 2- 0CH2tBu-4-CF3 5-CF3 14 -112 2-0(CH2)20Me-4-CF3 5-CF3 14-113 2-0(CH2)20Me-4-CF3 5-CN 14-114 2-0(CH2 ) 20CH20Me-4-CF3 5-CF3 14-115 2-0(CH2)20H-4-CF3 5-CF3 14-116 2-OCH2Ac-4-CF3 5-CF3 14-117 2-0CH2CH(0H)Me- 4-CF3 5-CF3 14-118 2-0CH2CH(0Me)Me-4-CF3 5-CF3 14-119 2-0CH2C(0H)Me2-4-CF3 5-CF3 14-120 2-0CH2C (OMe)Me2 -4-CF3 5-CF3 14-121 2-0CH2C(Me2)CO2Me-4-CF3 5-CF3 14-122 2-0CH2C(0)0Me-4-CF3 5-CF3 14 -123 2-0CH2C(0) 0Et-4-CF3 5-CF3 14-124 2-0(CH2)20Ac-4-CF3 5-CF3 14-125 2-0(CH2)2NH2-4-CF3 5-CF3 14-126 2-0(CH2 2NHAc-4-CF3 5-CF3 14-127 2-0(CH2)2NMe2-4-CF3 5-CF3 · 14-128 2-0CH2CH(Cl)Me-4-CF3 5-CF3 14-129 2-0CH2CH =CMe2-4-CF3 5-CF3 14-130 2-0CH2CH(Me)0Me-4-CF3 5-CF3 14-131 4-0CF3 5-CF3 14-132 3-0CF3 5-CF3 14-133 2-0 CF3 5-CF3 14-134 4-0CF2Br 5-CF3 14-135 3-0CF2Br 5-CF3 14-136 2-0CF2Br 5-CF3 14-137 2-0(CH2)2Br-4-CF3 5-CF3 14- 138 2-0(CH2)2Cl-4-CF3 5-CF3 14-139 2-0(CH2)2F-4-CF3 5-CF3 14-140 2-0CH2(Ph-4-Cl)-4-CF3 5 -CF3 14-141 2-0allyl-4-CF3 5-CF3 14-142 2-〇allenyl-4-CF3 5-CF3 14 -143 2-〇propargyl~4-CF3 5-CF3 149 1306016 Table 14 (Continued) )

Compound No. R 1 R 2 Physical Constant []: Melting Point °c 14-144 2-0(CH2)2CH=CH2-4-CF3 5-CF3 14-145 2-0CH2CH=CHMe-4-CF3 5-CF3 14- 146 2-0CH2CH=CMe2-4-CF3 5-CF3 14-147 2-0CH2C(Me)=CH2-4-CF3 5-CF3 14-148 2-0CH2CH=CHCl-4-CF3 5-CF3 14 -149 2 -0Ac-4-CF3 5-CF3 14-150 2-0C(0) ^-4-0?3 5-CF3 14-151 2-0S02Me-4-CF3 5-CF3 14-152 2-0S02Et-4- CF3 5-CF3 14-153 2-S02nPr-4-CF3 5-CF3 14 -154 2-0S02nBu-4-CF3 5-CF3 14-155 2-0S02NMe2-4-CF3 5-CF3 14 -156 2-0C( S)NMe2-4-CF3 5-CF3 14 -157 2-SC(0)NMe2-4-CF3 5-CF3 14 -158 2-NH2-4-CF3 5-CF3 14-159 2-N(nPr)2 -4-CF3 5-CF3 14-160 2-NHnPr-4-CF3 5-CF3 14-161 2-N(Me)nPr-4-CF3 5-CF3. 14-162 2-NHS02Me-4-CF3 5- CF3 14-163 2-NHS02Et-4-CF3 5-CF3 14-164 2-N(S02nBu) 2-4-CF3 5-CF3 14 -165 2-SnPr-4-CF3 5-CF3 14-166 2-SCH2cPr -4-CF3 5-CF3 14 -167 2-0P(0) (0Et)SnPr-4-CF3 5-CF3

150 1306016 NMR data Ή-NMR (CDC13) Compound No. 1-169 δ 1.85-1.95 (m, 2H), 2.05_2.24 (m, 2H), 3.57-3.65 (m, 2H), 3.93-4.01 (m, 4H), 4.62 - 4.69 (m, lH), 6.68 (d, lH), 6.86 (d, lH), 6.96 (a set of s and d, 2H), 7.63 (d, lH), 8.40 (s, lH) Compound No. 1-80 δ 1.98-2.05 (m, 4H), 3.69-3.78 (m, 2H), 3.86-3.94 (m, 2H), 4.82-4.86 (m, lH), 6.68 (d, lH), 7.10(d,lH), 7.63(d,lH),7.77(d,lH),7.86(s,lH),8.40(s,lH) Compound number 1-143 δ 1.89-2.06(m,4H),3.61 -3.70 (m, 2H), 3.91 - 4.00 (m, 2H), 4.63 - 4.67 (m, 1 H), 5.42 (d, 2H), 6.68 (d, lH), 6.85 (t, lH), 7.03 ( d, lH), 7.30 (d, lH), 7.36 (s, lH), 7.62 (d, 1H), 8.39 (s, 1H) Compound No. 1-163 δ 1.86-2.09 (m, 4H), 2.53 (t , lH), 3.57-3.66 (m, 2H), 3.94 - 4.03 (m, 2H), 4.60-4.67 (m, lH), 4.77 (d, lH), 6.68 (d, lH), 7.02 (d, lH) ), 7.24-7_29(m, 2H), 7.62 (d, lH), 8.39 (s, lH)

151 1306016 Compound No. 1_ 17 2 δ 1.29 (t, 3H), 1.83-1.94 (m, 2H), 2.04-2.14 (m, 2H), 3.15- 3.24 (m, 2H), 3.53-3.62 (m, 2H) , 3.95-4.0 l(m, 2H), 4.23 (brs, lH), 4.61-4.67 (m, lH), 6.68 (d, lH), 6.77 - 6.89 (m, 3H), 7.63 (d, lH), 8.40 (s, lH) Compound No. 1_ 6 9 δ 1.88-2.09 (m, 4H), 3.41 (s, 3H), 3.66-3.74 (m, 2H), 3.84-3.93 (m, 2H) 54.66 (s, 2H) ), 4.68-4.75 (m, 3H), 6.68 (d, lH), 6.95 (d, lH), 7.52 (d, lH), 7.63 (d, lH), 7.71 (s, lH), 8.4 0 (s) , lH) Compound No. 1 -1 7 3 δ 1.00 (t, 3H), 1.67 (q, 2H), 1.86-1.93 (m, 2H), 2.06- 2.12 (m, 2H), 3.07 - 3.15 (m, 2H) ), 3.5 5-3.63 (m, 2H), 3.93-4.01 (m, 2H), 4.32 (brs, lH), 4.64-4.66 (m, lH), 6-68 (d, lH), 6.77-6.90 ( m,3H), 7.63 (d, lH), 8.40 (s, lH) Compound No. 1-140 (5 1.87 - 2.06 (m, 4H), 3.60 - 3.68 (m, 2H), 3.84 (t, 2H), 3.86 - 3.99 (m, 2H), 4.30 (t, 2H), 4.63 - 4.68 (m, lH), 6.68 (d, lH), 7.03 (d, lH), 7.14 (s, lH), 7.22 (d, lH), 7.62 (d, lH), 8.40 (s, lH)

152 1306016 Compound No. 1-74 δ 1.91 — 2.08 (m, 4H), 3.42 (d, 2H), 3.74 - 3.86 (m, 4H), 4.69 - 4.71 (m, lH), 5.04 - 5.10 (m, 2H) , 5.91 - 6.00 (m, lH), 6.68 (d, lH), 6.92 (d, lH), 7.42 - 7.47 (m, 2H), 7.64 (d, lH), 8.41 (s, lH) 67 δ 0.97(t,3H), 1.74 - 1.95(m,4H),2.04 - 2.14(m,3H), 3.66 - 3.73(m,2H),3.85 - 3.94(m,2H),4.71 - 4.74 ( m,lH), 4.93 - 4.96 (m, 1 H), 6.69 (d, 1 H), 6.94 (d, lH), 7.49 (d, lH), 7.64 (d, lH), 7.69 (s, lH) , 8.40 (s, lH) Compound No. 2-57 δ 2.00 - 2.31 (m, 8H), 3.44 (s, 3H), 4.58 - 4.64 (m, 3H), 4.70 (s, 2H), 4.79 (s, 2H) ), 6.57 (d, lH), 6.72 (d, lH), 7.5 0 (d, lH), 7.63 (d, lH), 7.72 (s, lH), 8.41 (s, lH) Compound No. 2-58 δ 1.25 (t, 3H), 2.00 - 2.29 (m, 8H), 3.68 (q, 2H), 4.5 8 - 4.64 (m, 3H), 4.71 (s, 2H), 4.84 (s, 2H), 6.57 (d , lH), 6.72 (d, lH), 7.4 9 (d, lH), 7.63 (d, lH), 7.72 (s, lH), 8.41 (s, lH) Compound No. 2-78 δ 1.46 (t, 3H) ), 2.00 - 2.21 (m, 6H), 2.44 -

153 1306016 2.46(m,2H),4.10(q,2H),4.5 5(brs,2H),4.61(brs,lH),6'56(d,lH),6.78(d,lH),7.08(d5lH ), 7.15 (d5lH) 57.60 (d, lH), 8.40 (s, lH) Compound No. 2-141 δ 2.01 - 2.31 (m, 6H), 2.40 - 2.47 (m, 2H), 4.56 - 4.63 (m, 5H) ), 5.32 (d, lH), 5.46 (d, lH), 6.01 - 6.14 (m, lH), 6.55 (d, lH), 6.78 (d, lH), 7.1 l (s, lH), 7_17 (d , lH), 7. 61 (d, lH), 8_40 (s, lH) Compound No. 3-62 δ 1.78 - 1.93 (m, 4H), 2.14 - 2.19 (m, 4H), 3.28 (d, 2H), 4.69 (brs, 2H), 4.83 - 4.90 (m, 1 H), 4.95 - 5.02 (m, 2H), 5.77 - 5 · 91 (m, 1 H), 6.59 (d, 1H), 6.92 (d, lH ), 7.35 (s, lH), 7.41 (d, lH), 7.65 (d, lH), 8_43 (s, lH) Compound No. 2_ 148 δ 2.00-2.23 (m, 6H), 2.3 5-2.44 (m, 2H), 4.56-4.61 (m, 4H), 4.82 (q, lH), 6.06-6.64 (m, 2H), 6.56 (d, lH), 6.78 (d, lH), 7.12 (d, lH), 7.20 (d,lH),7_61(d,lH),8.40(s,lH) Compound number 2-144 δ 1.99-2.20(m,6H), 2.40-2.47(m,2H),2.57-2.64 (m,2H ), 4.07(t, 2H), 4.55-4.60 (m, 3H), 5.14 (dd, 2H), 5.86- 5.99 (m, lH), 6.56 (d, lH), 6.77 (d, lH), 7.08 ( s,lH), 154 1306016 7.12(d , lH), 7.60 (dd, lH), 8.40 (s, lH) Compound No. 2 -1 1 5 δ 2.00-2.30 (m, 7H), 2.35-2.44 (m, 2H), 3.97-4.03 (m, 2H ), 4.16 (t, 2H), 4.52-4.65 (brs, plus t, 3H), 6.5 6 (d, lH), 6.78 (d, lH), 7.14 (s, lH), 7.19 (d, lH), 7.62 (dd, lH), 8. 40 (s, lH) ® Compound No. 2-153 δ 1.05 (t, 3H), 1.76-1.84 (m, 2H), 2.03 (d, 2H), 2.17 - 2.20 (m , 2H), 2.36- 2.40 (m, 4H), 3.3 6 (t, 2H), 4.61 (brs, 2H), 4.72 (t, lH), 6.58 (d, lH), 6. 92 (d, lH) , 7.64 (d, lH), 7.80 (d, lH), 8.28 (s, lH), 8.42 (s, lH) Compound No. 2 - 112 (5 2.00 - 2.21 (m, 6H), 2.3 9-2.47 (m , 2H), 3.44(s,3H), _ 3.79(t,2H), 4.16(t,2H), 4.5 6(brs,2H),4.62(brs,lH),6.5 5(d,lH), 6_78 (d, lH), 7.12 (s, lH), 7_18 (d, lH), 7.61 (d, lH), 8.40 (s, lH) Compound No. 2 -1 6 1 δ 0.89 (t, 3 Η), 1.47 -1.63 (m, 2H), 2.07-2.1 l(m, 4H), 2.19- 2.27(m, 2H), 2.3 8-2.45(m, 2H), 2.80(s, 3H), 3.0 8(t, 2H ), 4.5 6 (brs, 2H), 4_60 (t, lH), 6_5 6 (d, lH), 6.72 (d, lH), 7. 15 (s, lH), 7.17 (d, lH), 7.60 ( Dd,lH), 8.40(s,lH) 155 i 1306016 Compound number 2-143 a δ 2.00-2.24(m,6H),2.3 8-2. 45 (m, 2H), 2.54-2.56 (m, lH), 4.56-4.63 (brs plus t, 3H), 4.77 (d, 2H), 6.56 (d, lH), 6.79 (d, lH), 7.22 ( s, lH), 7.25 (d, lH), 7.61 (dd, lH), 8.40 (s, 1H) Compound No. 2-138 δ 2.05-2.26 (m, 6H), 2.41-2.48 (m, 2H), 3.87 (t, 2H), # 4.31(t, 2H), 4.61-4.64 (brs plus t, 3H), 6.56 (d, lH), 6_80 (d, lH), 7.09 (s, lH), 7.20 (d, lH), 7.60 (dd, lH), 8.40 (s, lH) Compound No. 2-101 δ 2.11-2.40 (m, 8H), 4.5 8 (brs, 2H), 4.65 (t, lH), 4.86 (s, 2H), 6.57 (d, lH), 6.73 (d, lH), 7.27 (s, lH), 7.37 (d, l H), 7.62 (dd, lH), 8.41 (s, lH) • Compound No. 5- 175 δ 1.57-1.64 (m, 2H), 1.75 (d, 3H), 2.03-2.06 (m, 2H), 2.58 (brs, 2H), 3.08 (d, 2H), 4.18 (dd, 2H), 4.51 ( d, 2H), 4.62 - 4.67 (m, lH), 5.66-5.90 (m, 2H), 6.61 (d, lH), 7.01 (d, lH), 7.13 (s, lH), 7.20 (d, lH) , 7.62 (dd, lH), 8. 39 (s, lH)

156 1306016 Compound No. 5-89 δ 1.57-1.69 (m, 2H), 2.03-2.07 (m, 2H), 2.59 (brs, 2H), 3.10 (d, 2H), 3.89 (s, 3H), 4.18 (d) , 2H), 4.62 (s, lH), 6.61 (d, lH), 7.0 l (d, lH), 7.1 l (s5lH), 7.18 (d, lH), 7.62 (dd, lH), 8.39 (s, lH) Compound No. 5-90 δ 1.45 (t, 3H), l_57 - 1.68 (m, 2H), 2.03 - 2.07 (m, 2H), 2.5 8 (brs, 2H), 3.08 (d, 2H), 4.06 - 4.20 (m, 4H), 4.62 (s, lH), 6.60 (d, lH), 7.01 (d, lH), 7.11 (s, lH), 7.2 0 (d, lH), 7.62 (dd, lH) , 8.39 (s, lH) Compound No. 5-176 δ 1.55 - 1.63 (m, 2H), 2.02 - 2.04 (m, 2H), 2.55 - 2.62 (m, 4H), 3.08 (d, 2H), 4.07 (t , 2H), 4.15 (dd, 2H), 4.63 (s5lH), 5.16 (dd, 2H), 5.84 - 5,97 (m, lH), 6_60 (d, lH), 7.01 (d, lH), 7.12(s,lH),7.18(d,lH),7_w 62(dd,lH),8.39(s,lH) Compound number 5-139 (5 1.53 — 1.63(m,2H), 1.76(d,6H ), 2.02 - 2.07 (m52H), 2.5 8 (brs, 2H), 3.08 (d, 2H), 4.16 (dd, 2H), 4.5 7 (d52H), 4.62 (s, lH)? 5.46 (t, lH) , 6.60(d,lH),7.01(d,lH),7.13(s,lH)}7.1 8(d,lH), 7.62(dd,lH),8.3 9(s,lH)

157 1306016 Compound No. 5-123 δ 1.60 - 1.67 (m, 2H), 2.00 - 2.09 (m, 2H), 2.29 (brs, lH), 2.60 (brs, 2H), 3.1 l (d, 2H), 3.94 ( Brs, 2H), 4.08 - 4.22 (m, 4H), 4.62 (s, lH), 6.61 (d, lH), 7.04 (d, lH), 7_19 (s, lH), 7.20 - 7_30 (m, lH) , 7.62 (dd, lH), 8_39 (s, lH) Compound No. 5-147 δ 1.58 - 1.65 (m, 2H), 2.04 - 2.06 (m, 2H), • 2.5 8 (brs, 2H), 3.10 (d , 2H), 3.84 (t, 2H), 4.16 - 4.30 (m, 4H), 4.67 (s, lH), 6.61 (d, lH), 7.05 (d, lH), 7.16 (s, lH), 7.24 - 7.26 (m, lH), 7.62 (dd, lH), 8.40 (s, lH) Compound No. 5-124 δ 1.57 - 1.69 (m, 2H), 2.02 - 2.05 (m, 2H), 2.57 (brs, 2H) , 3-〇9(d,2H), 3.43(s,3H),3.77(t,2H),4.13 - 4.20(m,4H),4.65(s,lH),6.60(d,lH), 7.02( d,lH), • 7_16(s,lH),7_17 - 7.25(m, 1 H), 7.62(dd, 1H), 8.39 (s,lH) Compound No. 5-132 δ 1.57 - 1.66(m,2H) , 2.00 - 2.06 (m, 2H), 2.59 (brs, 2H), 3.11 (d, 2H), 3.79 (s, 3H), 4.12 - 4.22 (m, 2H), 4.65 - 4.69 (m, 3H), 6.60 (d,lH), 7.05(d,lH), 7.1 3(s, 1 H), 7.21 - 7.2 8(m,lH), 7.62(dd,lH),8.39(s,lH) 1306016 Compound 5-134 δ 1.58 - 1.64 (m, 2H), 1.95 - 2.13 (m, 2H), 2.06 (s, 3H), 2.58 (brs, 2H), 3.09 (d, 2H), 4.16 - 4.2 5 (m, 4H), 4.44 (t, 2H), 4.63 (s, lH), 6.61 (d, lH), 7.04 (d, lH), 7.16 (s, 1H), 7.22 - 7.29 (m, lH) , 7.62 (dd, lH), 8.39 (s, lH) Compound No. 5 -13 3 δ 1.31 (t, 3H), 1.59 - 1.65 (m, 2H), 2.04 - 2.07 (m, 2H), • 2.60 (brs , 2H), 3.10 (d, 2H), 4.14 - 4.30 (m, 4H), 4.68 (s, 3H), 6.61 (d, lH), 7.05 (d, lH), 7.13 (s, lH), 7.25 - 7.28(m,lH),7_62(dd,lH),8.39(s,lH) Compound number 5 -16 3 δ 1.15(t,3H),1.62 - 1.69(m,2H),1.99 - 2.12(m,4H ), 2.64 (brs, 2H), 3.14 (d, 2H), 3.32 (t, 2H), 4.23 (dd, 2H), 4.64 (s, lH), 6.62 (d, lH), 7.14 (d, lH) , 7.53 (d, lH), 7.54 (s, lH), 7.64 (dd, lH), 8. 41 (s, lH) Compound 5-126 5 1.63 - 1.68 (m, 2H), 1.93 - 2.04 (m, 2H), 2.35(s,3H), 2.61(brs,2H)53.12(d,2H)54.21(dd,2H),4.5 8(s,2H),4.66(s,lH), 6.62(d,lH) , 7.05 (s-like, 2H), 7.26 (s-like, lH), 7_63 (dd, lH), 8.40 (s, lH)

159 1306016 Compound 5-127 δ 1.27(d,3H), 1.59 - 1.67(m,2H), 2.00 - 2.04(m,2H), 2.61(brs,3H),3.12(d,2H),3.81(t, lH), 4.04 (dd, lH), 4.08 - 4.22 (m, 3H), 4.62 (s, lH), 6.61 (d, lH), 7.03 (d, lH), 7.12 (s, lH), 7.20 (s) -like,lH), 7.63 (dd, lH), 8.40 (s, lH) Compound 5-128 δ 1.28 (d, 3H), 1.5 7-1.64 (m, 2H), 2.01-2.04 (m, 2H), # 2.5 8(brs,2H),3.09(d,2H), 3.46(s,3H),3.69 - 3.80 (m,lH),3.91 — 4.04(m,lH)54.18(brd,2H), 4.64(s , lH), 6.61 (d, lH), 7.01 (d, lH), 7.12 (s, lH), 7.16 (d, lH), 7.62 (dd, lH), 8. 39 (s, lH) 129 5 1.28(s,6H),1.56-1.67(m,2H),1.99-2.04(m,2H), 2.46(s,lH), 2.60(brs,2H),3.1 l(d,2H),3.85 (s, 2H), 4.20 (dd, 2H), repair 4.62 (s, lH), 6.62 (d, lH), 7.02 (d, lH), 7.14 (s, lH), 7.18 (s-Hke, lH) , 7.63 (dd, lH), 8.40 (s, lH) Compound 5-130 δ 1.3 3 (s, 6H), 1.5 8-1.64 (m, 2H), 2.02-2.05 (m, 2H), 2.5 8 (brs , 2H), 3.10 (d, 2H), 3.31 (s, 3H) J3.87 (sJ2H), 4.18 (dd, 2H), 4.65 (s, lH), 6.61 (d, lH), 7.01 (d, lH) ), 7.13 (s, lH), 7.18 (d, lH), 7.6 2 (dd, lH), 8.40 (s, lH) 160 1306016 Compound 5-114 δ 1.37 (d, 3H), 1.57-1.64 ( m, 2H), 1.77-1.90 (m, lH), 2.03-2.05 (m, 2H), 2.04 (s, 3H), 2.57 (brs, 2H), 3.09 (d, 2H) , 3.57(t,lH),4.03 - 4.20(m,2H),4.62(s, 1H), 5.25 - 5.35(m,lH),6.61(d,lH), 7.02(d,lH), 7.13(s , lH), 7.22 (d, lH), 7.62 (dd, lH), 8.39 (s, lH) Compound 5-138 δ 1.58-1.70 (m plus d, 5H), 2.02-2.05 (m, 2H), 2.58 (brs, 2H), 3.10 (d, 2H), 4.03 - 4.21 (m, 4H), 4.28-4.3 8 (m, lH), 4.66 (s, lH), 6.61 (d, lH), 7.04 (d, lH), 7.13 (s, lH), 7.17 (d, lH), 7.62 (dd, lH), 8.40 (s, lH) Compound 5-98 δ 1.06 (t, 3H), 1.80-1.92 (m, 2H) , 2.01-2.04 (m, 4H), 2.5 7 (brs, 2H), 2.93 (d, 2H), 3.97 (t, 2H), 4.18 (dd, 2H), 4.5 7 (s, lH), 6.85 (d5lH ), 7.01 (d, lH), 7.1 l (s, lH), 7.17 (d, lH), 7.35 (dd, lH), 8. 40 (s, lH) Compound 5-202 δ 1.41 (t, lH) , 1.59-1.66 (m, 2H), 1.77 (t, lH), 2.05-2.22 (m, 3H), 2.60 (brs, 2H), 3.1 l (dd, 2H), 4.05 (t, lH), 4.19 ( Dd,2H),4.2 9(dd,lH),4.66(s,lH)56.61(d,lH),7.05(d,lH),7.14(s,lH),7.23(d-like,lH),7.62 (dd, lH), 8.39 (s, lH)

161 1306016 Compound 6-82 δ 0.92 (t, 3H), 1.42-1.47 (m, lH), 1.5 7-1.80 (m, 5H), 1.98-2.04 (m, 2H), 2.35 (brs, 2H), 3.55 (dd, 2H), 3.93 (t, 2H), 4.08 (d, 2H), 4.48 (t, lH), 6.62 (d, lH), 6.99 (d, lH), 7.09 (s, l H), 7.12 (d, lH), 7.62 (dd, lH), 8.42 (s, lH) Compound 7-103 δ 0.3 5-0.40 (m, 2H), 0.61-0.67 (m, 2H), l, 24-1.36 • ( m, lH), 1.45-1.51 (m, lH), 1.5 7-1.63 (m, 2H), 1.67-1.8 8 (m, lH), 2.18-2.31 (m, 4H), 3.25 (d, 2H), 3.91 (d, 2H), 4.46 (d, 2H), 4.62 (s, lH), 6.66 (d, lH), 7.02 (d, lH), 7.12 (s, lH), 7.18 (d, lH), 7.63 (dd, lH), 8.42 (s, lH) Compound 2-130 δ 1.31 (d, 3H), 2.00-2.22 (m, 6H), 2.40-2.50 (m, 2H), 3.45 (s, 3H), 3.72 -3.81 (m,lH),3.8 8-3.93 (m,lH), 4.01-4.06(m,lH),4.5 6-4.61(m+brs,3H),6.5 6 (d,lH), 6.77 (d , lH), 7.10 (s, lH), 7.17 (d, lH), 7.61 (dd, lH), 8.40 (s, lH) Compound 1-98 δ 1.05 (t, 3H), 1.13 (d, 3H), 1.71-1.91(m,4H),2.05-2.15 (m,2H), 3.00 (dd,lH),3.22-3.3 0(m,lH), 3.98(t,2H), 4.10- 4.24(m,2H) , 6.67(d,lH), 6.98(d, 1 H),7.1 0(d, 1H), 7.16(d,lH), 7.61(dd,lH),8.3 9(s,lH)

162 1306016 Compound 5-118 δ 0.36 (q, 2H), 0.63 (q, 2H), 1.19-1.3 l (m, lH), 1.55-1.63 (m, 2H), 2.07 (brt, 2H), 2.57 (brs) , 2H), 3.07 (d, 2H), 3.87 (d, 2H), 4.1 7 (dd, 2H), 4.63 (s, lH), 6.59 (d+q, 2H), 6.99-7.03 (m, 3H) , 7.61 (dd, lH), 8.39 (s, lH) Compound 6-4 δ 1.40-1.56 (m, lH), 1.75-1.86 (m, 3H), 1.91-2.05 • (m, 2H), 2.61 (brs) , 2H), 3.40 (dd, 2H), 4.16 (d, 2H), 4.56 (t, lH), 5.81 (s, lH), 6.62 (d, lH), 6_91 (d, lH), 7.13 (d, lH), 7.19 (s, lH), 7.63 (dd, 1H), 8.42 (s, 1H) Compound 2-90 <5 1.08 (t, 3H), 1.81-1.93 (m, 2H), 1.97- 2.09(m,4H), 2.16- 2.24(m,2H), 2.40-2.46(m,2H),2.98(s,3H), 3.97

(t, 2H), 4.48 (brs, 2H), 4.5 9 (t, lH), 6.57 (d, lH), 6.77 (d, lH), 7.07 (s, lH), 7.14 (d, lH), 7.51 (dd,lH), 8.07(s,lH) Compound 2-167 δ 0.98(t,3H), 1.42(t,3H),1.67-1.75(m,2H),2.01-2.23 (m,6H),2.42 (d, 2H), 2.87-2.97 (m, 2H), 4.28-4.3 5 (m, 2H), 4.57 (brs, 2H), 4.62 (t, lH), 6.5 6 (d, lH), 6.84 (d , lH), 7.39 ( d, lH), 7.62 (dd, lH), 7.70 (s, lH), 8.41 (s, lH) 163 1306016 Compound 1-95 % - δ 1.02-1.16 (m, 8H), 1.26 (s,3H)) 1.79-1.94 ' / (m,4H), 3.30 (m,lH), 3.80 (d,lH), 3.90-3.99 (m,2H),4.08 (q,2H),4.13-4.3 8(m,2H), 4.77(brs,lH), 6.71(d,lH), 7.06(s,lH),7.09(d,lH),7.16(d,lH), 7.60(dd,lH),8.37 (s, lH) Compound 5-93 δ 1.06 (t, 3H), 1.63-1.69 (m, 2H), 1.74-1.88 (m, 2H), 2.00- _ 2.02 (m, 2H), 2.55 (brs, 2H) ), 3.01(d,2H), 4.00 (t,2H),4.07- 4.16(m,2H), 4.38(s,2H), 4.59(s, 1 H), 6.59 (d,lH),7.01(d5lH ), 7.10 (s, lH) 57.13 (d, lH), 7.50 (dd, lH), 8.12 (s, 1H) Compound 2-81 δ 1.09 (t, 3H), 1.84-2.21 (m, 8H), 2.40 -2.43 (m, 2H), 3.97 (t, 2H), 4.5 6-4.62 (brm, 3H), 6.56 (d, lH),

6.73(d,lH),7.08(s,lH),7.23(m,lH), 7.62(dd,lH),8.41(s,lH) Compound 2-67 δ 2.00-2.21 (m,4H),2.28- 2.35 (m, 4H), 4.59 (brs, 2H), 4.66 (t, lH), 6.5 8 (d, lH), 6.8 8 (d, lH), 7.63 (dd, lH), 7.74 (d, lH) , 7.86 (s, lH), 8.41 (s, lH)

164 1306016 Compound 5-99 δ 1.06(t,3H), 1.5 8-1.63 (m, 2H), 1.65-1.89 (m, 2H), 2.02-2.04 (m, 2H), 2.5 7 (brs, 2H), 3.06(d,2H), 4.00(t,2H), 4.16(d,2H),4.62(s,lH),6.5 7(t,lH),6.63(d5lH),7.01 (d,lH),7.1 l (s, lH), 7.17 (d, lH), 7.60 (dd, lH), 8.24 (s, lH) Compound 5-103 δ 1.04 (t, 3H), 1. 57-1.64 (m, 2H), 1.77 -1.88(m,2H), 1.96-Φ 2.04(m,2H),2.5 8(brs,2H), 3.13 (d,2H),3.91(t,2H),4.17(d,2H),4_5 2( s, lH), 6.61 (d, lH), 6.63 (d, lH), 6.75 (s-like, 2H), 7.63 (dd, lH), 8.40 (s, lH) Compound 5-101 5 1.06 (t, 3H), 1.47-1.67 (m, 3H), 1.79-1.91 (m, 2H), 2.01-2.04 (m, 2H), 2.56 (brs, 2H), 3.03 (d, 2H), 3.97 (t, 2H) , 4.09 (dd, 2H), 4.57 (brs, 2H), 4.60 (s, lH), 6.61 • (d, lH), 7.01 (d, lH), 7.1 l (s, lH), 7.17 (d, lH) ), 7.52 (dd, lH), 8.14 (s, 1H) Compound 5-4 δ 1.69 (m, 2H), 1.97 (m, 2H), 2.65 (bs, 2H), 3.14 (d, 2H), 4.24 ( Dd, 2H), 4.65 (s, lH), 5.65 (s, lH), 6.63 (d, lH), 6.99 (d, lH), 7. 14 (d, lH), 7.20 (s, lH), 7.65 (d, lH), 8.40 (s, lH) 1306016 Compound 5-177 δ 1.62 (m, 2H), 2.04 (m, 2H), 2.5 3 (s, lH), 2.60 (bs, 2H), < 3.10 (d, 2H), 4.19 (dd, 2H), 4.63 (s, lH), 4.77 ( s, 2H), 6.61 (d, lH), 7. 04 (d, lH), 7.27 (m, 2H), 7.62 (d, lH), 8.40 (s, lH) Compound 5-75 (5 1.63 (m) , 2H), 1.98 (m, 2H), 2.61 (bs, 2H), 3.15 (d, 2H), 3.37 (d, lH), 3.68 (d, lH), 4.20 (dd, 2H), 4.61 (s, lH), 5.07 (d, 2H), 5. ® 93 (m, lH), 6.63 (d, lH), 6.97 (d, lH), 7.41 (s, lH), 7.45 (d, lH), 7.63 ( d,lH), 8.41(s,lH) Compound 5-69 δ 1.65 (m, 2H), 1.94 (m52H), 2.61 (bs, 2H), 3.15 (d, 2H), 3.43 (s, 3H), 4_21 (dd, 2H), 4.63 (m, 3H), 4_77 (s, 2H), 6.62 (d, lH), 7. 00 (d, lH), 7_5 3 (d, lH), 7.65 (d, lH) , 7.70 (d, lH), 8.40 (s, lH)

Compound 5-131 δ 1.35 (s, 6H), 1.5 8 (m, 2H), 2.02 (m, 2H), 2.55 (bs, 2H), 3.07 (d, 2H), 3.68 (s, 3H), 4.02 ( s, 2H), 4.15 (dd, 2H), 4.5 8 (s, lH), 6.61 (d, lH), 6.99 (d, lH), 7.10 (s, lH), 7.19 (d, lH), 7.62(d,lH), 8.39( s,lH) Compound 5-137 δ 1.62 (m, 2H), 2.03 (m, 2H), 2.3 6 (s, 6H), 2.5 8 (bs, 2H),

166 1306016 2.77(t,2H), 3.09(d,2H), 4.14(m,4H),4.63(s,lH),6.60(d,lH),7.0 0(d,lH),7.14(s,lH ), 7.20 (d, lH), 7.63 (d, lH), 8.40 (s, lH) Compound 5-136 δ 1.65 (m, 2H), 2.00 (m, 5H), 2.60 (bs, 2H), 3.1 l (d, 2H), 3.67 (q, 2H), 4-10 (t, 2H), 4.21 (dd, 2H), 4.62 (s, lH), 5.94 (bs, lH), 6. 62 (d, lH) ), 7.05 (d, lH), 7.15 (s, lH), 7.23 (d, lH), 7.63 (d, lH), 8.40 (s, lH) Compound 5-73 δ 1.41 (d, 3H), 1.65 ( d, 2H), 1.97 (m, 2H), 2.62 (bs, lH), 3.15 (d, 2H), 3.37 (s, 3H), 4.20 (m, 2H), 4.62 (m, 3H), 5.08 (q) , lH), 6. 63 (d, lH) 56.97 (d, lH), 7.49 (d, lH), 7.63 (d, lH), 7.73 (s, lH), 8.40 (s, lH) Compound 5-229 NMR NMR (CDC13) δ 1.22 (t, 3H) 51.40 (d, 3H), 1.60-1.66 (m, 2H), 1.95-1.99 (m, 2H), 2.61 (brs, 2H) 5 3.14 (d, 2H) , 3.49-3.5 9(m,lH), 3.63-3.73(m,lH), 4.22 (dd,2H),4.50- 4_66(m,3H),4.86(q,lH), 6.62 (d,lH), 6.98(d,lH),7_51(dd,lH),7_63(dd,lH),7.71(s,lH),8.40 Compound 9-94 'H NMR(CDC13) δ 1.09(t,3H),1.63-1.75 (m, 2H), 1.84

167 1306016 1.95 (m, 2H), 2.04-2.10 (m, 2H), 3.19-3.28 (m, 2H), 3.54-3.62 (m, lH), 4.03 (t, 2H), 4.21-4.28 (m, 2H) ), 6.64(d,lH), ^7.04(s,lH),7.16(d,lH),7_40(d,lH),7.61(dd,lH),8.38(s,lH) Compound 11-93 Ή NMR (CDC13) δ 1.08(t,3H), 1.79-1.95(m,8H), 2.10-2.17(m,2H),3.85_3.96(m,lH),4.01(t,2H), 4.61 (brs, 2H), 6.52 (d, lH), 7.01 (s, lH), 7.12 (dd, lH), 7.35 (d, lH), 7.60 # (dd, lH), 8.39 (s, lH) Compound 5-246 Ή NMR (CDC13) δ 1.63-1.68 (m, 2H), 1.96-2.03 (m, 2H), 2.62 (brs, 2H), 2.90 (t, 2H), 3.15 (d, 2H), 3.3 5 (s, 3H) ), 3. 5 7 (t, 2H), 4.22 (dd, 2H), 4.60 (s, lH), 6.63 (d, lH), 6.96 (d, lH), 7.44 (s, lH), 7.45 (d) , lH), 7.63 (dd, lH), 8.40 (s, lH) Compound 5-247 (trans/cis = 59/41) Trans Ή NMR (CDC13) δ 1.56-1.68 (m, 2H), 1.98 _ 2.06 (m, 2H), 2.62 (brs, 2H), 3_13 (d, 2H), 3.70 (s, 3H), 4.20 (d, 2H), 4.63 (s5lH), 5.95 (d, lH), 6.61 ( d, lH), 6.98 (d, lH), 7.16 (d, lH), 7.3 6 (d, lH), 7.49 (s, lH), 7.64 (dd, lH), 8.40 (s, lH) cis Ή NMR (CDC13) δ 1.56-1.68 (m, 2H), 1.98-

168 1306016 2.06 (m, 2H), 2.62 (brs, 2H), 3.13 (d, 2H), 3.81 (s, 3H), 4.20 (d, 2H), 4.60 (s, lH), 5.5 6 (d, lH) ), 6.23 (d, lH), 6.61 (d, lH), 6.95 (d, lH), 7.3 6 (d, lH), 7.64 (dd, lH), 8.31 (s, lH), 8.40 (s, lH) Compound 2-203 *H NMR (CDC13) δ 1.36 (t, 3H), 1.99-2.35 (m, 8H), 4.27 (q, 2H), 4.59 (brs, 2H), 4.65 (t, lH), 6.57 (d, lH), 6.76 (d, lH), 7. 54 (dd, lH), 7.63 (dd, lH), 8.1 1 (s, 1H), 8.41 (s, 1H), 8.43 (s, 1H) Compound 2-224 Ή NMR (CDC13) δ 1.36 (t, 3H), 1.83 (s, 3H), l_92-2.07 (m, 4H), 2.15-2.29 (m, 4H), 4.26 (q, 2H), 4.53 (brs, 2H), 4.60 (t, lH), 6.54 (d, lH), 6.76 (d, lH), 7.04 (s, lH), 7.24 (d, lH), 7.61 (dd, lH), 8.40 ( s,lH) Compound 2-148 δ 2.00-2.23(m,6H),2.3 5-2.44(m,2H),4.56-4.61 (m,4H), 4.82 (q,lH), 6.06-6.64 (m, 2H), 6.56 (d, lH), 6.78 (d, lH), 7.12 (d, lH), 7.20 (d, lH), 7.61 (d, lH), 8.40 (s, lH) Compound 2-144 δ 1.99 -2.20(m,6H), 2.40-2.47(m,2H), 2.57-2.64 (m,2H),4'07(t,2H),4.5 5-4.60(m,3H),5.14(dd,2H ), 5.86- 5.99 (m, lH), 6.56 (d, lH), 6.77 (d, lH), 7.08 (s, lH), 169 1306016 7_12 (d, lH), 7.60 (dd, lH), 8.40 (s, lH) • r / compound 2-115 δ 2.00-2.30 (m, 7H), 2.3 5-2.44 (m, 2H), 3.97-4.03 (m, 2H), 4.16 ( t, 2H), 4.52-4.65 (brs plus t, 3H), 6.56 (d, lH), 6.78 (d, lH), 7.14 (s, lH), 7.19 (d, lH), 7.62 (dd, lH) , 8.40(s, 1H) Compound 2-153 δ 1.05(t,3H),1.76-1.84(m,2H),2.03(d,2H),2.17-2.20 (m,2H),2.3 6-2.40(m , 4H), 3.36 (t, 2H), 4.61 (brs, 2H), 4.72 (t, lH), 6.5 8 (d, lH), 6.92 (d, lH), 7.64 (d, lH), 7.80 (d , lH), 8.2 8 (s, lH), 8.42 (s, lH) Compound 2-112 δ 2.00-2.2 l (m, 6H), 2.39-2.47 (m, 2H), 3.44 (s, 3H), 3.79 (t, 2H), 4.16 (t, 2H), 4.5 6 (brs, 2H), 4.62 (brs, lH), 6.5 5 (d, lH) J 6.78 (d, lH), 7.12 (s, lH), 7_18(d,lH), 7.61(d,lH), 8.40(s,lH) Compound 2-161 δ 0.89(t,3H), 1.47-1.63(m,2H),2.07-2.1 l(m,4H) , 2.19- 2.27(m,2H),2.3 8-2.45(m,2H), 2.80(s,3H), 3.08(t,2H),4.5 6(brs,2H),4.60(t,lH),6.5 6(d,lH), 6.72(d,lH), 7.15(s,lH),7.17(d,lH), 7.60(dd,lH),8.40(s,lH)

170 1306016 Compound 2-143, δ 2.00-2.24(m,6H), 2.38-2.45(m,2H),2.54-2.56 r (m,lH),4.56-4.63(brs plus t,3H),4.77(d , 2H), 6.56 (d, lH), 6.79 (d, lH), 7.22 (s, lH), 7.25 (d, lH), 7.61 (dd, lH), 8.40 (s, 1H) Compound 2-138 δ 2.05-2.26(m,6H), 2.41-2.48(m,2H), 3.87 • (t,2H)54.31(t,2H),4.61-4.64(brs plus t,3H),6.56 (d,lH), 6.80(d,lH), 7.09(s,lH), 7.20(d,lH), 7.60(dd,lH), 8.40(s, 1H) Compound 2-101 5 2.1 l-2.40(m,8H),4.5 8 (brs, 2H), 4.65 (t, lH), 4.86 (s, 2H), 6.57 (d, lH), 6.73 (d, lH), 7.27 (s, lH), 7.37 (d, lH), 7.62 (dd, 1H), 8.41 (s, 1H) Compound 5-175 δ 1.5 7-1.64 (m, 2H), 1.75 (d, 3H), 2.03-2.06 (m, 2H), 2.5 8 (brs, 2H) , 3.08(d,2H), 4.18(dd,2H), 4.51(d,2H),4.62-4_67(m,lH),5.66-5_90(m,2H),6.61(d,lH), 7.01(d , lH), 7.13 (s, lH), 7.20 (d, lH), 7.62 (dd, lH), 8.39 (s, lH)

171 1306016 Compound 5-89 ft-δ 1.57-1.69 (m, 2H), 2.03-2.07 (m, 2H), 2.59 (brs, 2H), · / 3.10 (d, 2H), 3.89 (s'3H), 4.18(d,2H), 4.62(s,lH),6.61(d,lH),7.0 l(d,lH),7.11(s,lH),7.18(d,lH), 7.62(dd,lH), 8.39(s,lH) Compound 5-90 δ 1.45(t,3H), 1.5 7-1.68(m,2H),2.03-2.07(m,2H),2.58 (brs,2H)J3.08(d,2H ), 4.06-4.20 (m, 4H), 4.62 (s, lH), Φ 6.60 (d, lH), 7.01 (d, lH), 7.1 l (s, lH), 7.20 (d, lH), 7.62 ( Dd, lH), 8. 39 (s, lH) Compound 5-176 5 1.55-1.63 (m, 2H), 2.02-2.04 (m, 2H), 2.55-2.62 (m, 4H), 3.08 (d, 2H) ), 4.07 (t, 2H), 4.15 (dd, 2H), 4.63 (s, lH), 5.16 (dd, 2H), 5.84-5, 97 (m, lH), 6.60 (d, lH), 7.01 ( d,lH),7.12(s5lH),7.18(d,lH),7.62(dd,lH)58.3 9(s,lH) Compound 5-139 δ 1.5 3-1.63(m,2H),1.76(d,6H ), 2.02-2.07 (m, 2H), 2.5 8 (brs, 2H), 3.08 (d, 2H), 4.16 (dd, 2H), 4.5 7 (d, 2H) J4.62 (s, lH) J 5.46 (t,lH), 6.60(d,lH),7.01(d,lH),7.13(s,lH),7.18(d,lH)s7.6 2(dd,lH),8.39(s,lH)

172 1306016 Compound 5-123 - δ 1.60-1.67 (m, 2H), 2.00-2.09 (m, 2H), 2.29 (brs, 1 Η), 2.60 (brs, 2H), 3.11 (d, 2H), 3.94 ( Brs, 2H), 4.08-4.22 (m, 4H), 4.62 (s, lH), 6.61 (d, lH), 7.04 (d, lH), 7.19 (s, lH), 7.2 0-7.30 (m, lH ), 7.62 (dd, lH), 8.39 (s, lH) Compound 5-147 δ 1.5 8-1.65 (m, 2H) 52.04-2.06 (m, 2H), 2.58 (brs, 2H), ® 3.10 (d, 2H), 3.84(t,2H), 4.16-4.30(m,4H), 4.67(s,lH), 6.61(d,lH),7.05(d,lH),7.16(s,lH),7.24-7.26 (m, lH), 7.62 (dd, lH), 8.40 (s, lH) Compound 5-124 δ 1.57-1.69 (m, 2H), 2.02-2.05 (m, 2H), 2.57 (brs, 2H), 3.09 (d, 2H), 3.43 (s, 3H), 3.77 (t, 2H), 4.13-4.20 (m, 4H), 4.65 (s, lH), 6.60 (d, lH), 7.02 (d, lH), 7.16(s,lH),7.17-7.25(m,lH), 7.62(dd,lH),8.3 9(s,lH) Compound 5-132 δ 1.57-1.66 (m, 2H), 2.00-2.06 (m, 2H), 2.59 (brs, 2H), 3.1 l(d, 2H), 3.79 (s, 3H), 4.12-4.22 (m, 2H), 4.65- 4.69 (m, 3H), 6.60 (d, lH), 7.05(d,lH), 7.13(s,lH), 7.21- 7.28(m,lH),7.62(dd,lH),8.3 9(s,lH) 173 1306016 Compound 5-134-δ 1.5 8-1.64( m, 2H), 1.95-2.13 (m, 2H), 2.06 (s, 3H), V 2.5 8 (brs, 2H), 3.09 (d, 2H), 4.16-4.25 (m, 4H), 4.44 (t, 2H)5 - 4.63(s,lH), 6.61(d,lH),7.04(d,lH),7.16(s,lH ), 7.22 - 7.29 (m, lH), 7.62 (dd, lH), 8.39 (s, lH) Compound 5-133 δ 1.31 (t, 3H), 1.59-l_65 (m, 2H), 2.04-2.07 (m) , 2H), 2.60 ® (brs, 2H), 3.10 (d, 2H), 4.14 - 4.3 0 (m, 4H), 4.68 (s, 3H), 6.61 (d, lH), 7.05 (d, lH)} 7.13(s,lH), 7.25-7.28(m,lH)5 7.62(dd,lH),8.39(s,lH) Compound 5-203 δ 1.5 7-1.64(m,2H),2.01-2.09(m, 2H), 2.57 (brs, 2H), 3.10 (d, 2H), 3.93-4.21 (m, 8H), 4.64 (s, lH), 5.32 (t, lH), 6.61 (d, lH), 7.01 (d) , lH), 7.17 (s, lH), 7.21-7.26 (m, lH), • 7.62 (dd, lH), 8.39 (s, lH) Compound 5-163 δ 1.15 (t, 3H), 1.62-1.69 ( m, 2H), 1.99-2.12 (m, 4H), 2.64 (brs, 2H), 3.14 (d, 2H), 3.32 (t, 2H), 4.23 (dd, 2H), 4.64 (s, lH), 6.62 (d, lH), 7.14 (d, lH), 7.53 (d, lH), 7.54 (s, lH), 7.64 (dd, lH), 8. 41 (s, lH) 174 1306016 Compound 5-204 δ 1.59 -1.70 (m, 2H), 1.85-2.09 (m, 6H), 2.57, 2.64 (two s, total 2H), 3.12 (t-like, 2H), 3.82 (q, lH), 3.93 (q, lH) , 4.02(d,2H),4.1 l-4.30(m,3H),4.64(s,lH),6.60 (d,lH)57.01(d,lH),7.14(s,lH),7.17(d,lH ), 7.62 (dd, lH) 38.40 (s, 1H) Compound 5-126

δ 1.63-1.68 (m, 2H), 1.93-2.04 (m, 2H) 52.3 5 (s, 3H), 2.61 (brs, 2H), 3.12 (d, 2H), 4.21 (dd, 2H) > 4.5 8 (s, 2H), 4.66 (s, lH), 6.62 (d, lH), 7.05 (s-like, 2H), 7.26 (s-like, lH), 7.63 (dd, lH), 8.40 (s, lH) Compound 5-127 δ 1.27 (d, 3H), 1.59-1.67 (m, 2H), 2.00-2.04 (m, 2H), 2.61 (brs, 3H), 3.12 (d, 2H), 3.Bl (t , lH), 4.04 (dd, lH), 4.08-4.22 (m, 3H), 4.62 (s, lH), 6.61 (d, lH), 7.03 (d, lH), 7.12 (s, lH), 7.20 ( S-like, lH), 7.63 (dd, lH), 8.40 (s, lH) Compound 5-128 δ 1.28 (d, 3H), 1.57-1.64 (m, 2H), 2.01-2.04 (m, 2H), 2.5 8 (brs, 2H), 3.09 (d, 2H), 3.46 (s, 3H), 3.69-3.80 (m, lH), 3.91-4.04 (m, lH), 4.18 (brd, 2H), 4.64 (s , lH), 6.61 (d, lH), 7.01 (d, lH), 7.12 (s, lH), 7.16 (d, lH), 7.62 (dd, lH), 8.39 (s, 175 1306016 1H) 129 δ 1.28(s,6H),1.56-1.67(m,2H),1.99-2.04(m,2H), 2.46(s,lH), 2.60(brs,2H),3.1 l(d,2H),3.85 (s, 2H), 4.20 (dd, 2H), 4.62 (s, lH), 6.62 (d, lH), 7.02 (d, lH), 7.14 (s, lH), 7.18 (s-like, lH), 7.63(dd,lH), 8.40(s,lH) Compound 5-130 δ 1.33(s,6H),1.5 8-1.64(m,2H),2.02-2.05(m,2H), 2.5 8(brs,2H ), 3.10 (d, 2H), 3.31 (s, 3H), 3.87 (s, 2H), 4.18 (dd, 2H), 4.65 (s, lH), 6.61 (d, lH), 7.01 (d, lH) , 7.13 (s, lH), 7.1 8(d,lH),7.6 2(dd,lH), 8.40(s,lH) Compound 5-114 δ 1.37(d53H)51.5 7- 1.64(m,2H),1.77-1.90(m,lH), 2.03 - 2.05(m,2H),2.04(s,3H),2.5 7(brs,2H), 3.09 (d,2H),3.5 7(t,lH),4.03-4.20(m,2H),4.62(s , lH), 5.25-5.3 5 (m, lH), 6.61 (d, lH), 7.02 (d, lH), 7.13 (s, lH), 7.22 (d, lH), 7. 62 (dd, lH) , 8.39 (s, lH) Compound 5-138 δ 1.58-1.70 (m plus d, 5H), 2.02-2.05 (m, 2H), 2.5 8 (brs, 2H), 3.10 (d, 2H), 4.03-4.21 (m, 4H), 4.28- 176 1306016 4.38 (m, lH), 4.66 (s, lH), 6.61 (d, lH), 7.04 (d, lH), 7.13 (s, lH), 7.1 7 (d, lH), 7.62 (dd, lH), 8.40 (s, lH) Compound 5-206 δ 1.5 8-1.63 (m, 2H), 2.00-2.04 (m, 2H), 2.56 (brs, 2H), 3.06 (d , 2H), 4.17 (dd, 2H), 4.62 (s, lH), 5.05 (s, 2H), 6.34-6.41 (m, 2H), 6.60 (d, lH), 7.02 (d, lH), 7.22 ( S-like,2H), 7.43(s,lH), 7.62(dd,lH),8.39(s,lH)

Compound 5-208 δ 1.57-1.64 (m, 2H), 2.00-2.04 (m, 2H), 2.58 (brs, 2H), 3.06 (d52H), 4.17 (dd, 2H), 4.62 (S) lH), 5.12 (s, 2H), 6.61 (d, lH), 7. 03 (d, lH), 7.14 (d, lH), 7.20-7.21 (m, 2H), 7.31-7.3 5 (m, 2H), 7.62 ( Dd,lH), 8.39(s,lH) Compound 5-207 δ 1.5 7-1.64 (m, 2H), 2.00-2.03 (m, 2H), 2.57 (brs, 2H), 3.07 (d, 2H), 4.18 (dd, 2H), 4.62 (s, lH), 5.00 (s, 2H), 6.47 (s, lH), 6. 60 (d, lH), 7.03 (d, lH), 7.21 (d-like, 2H) ), 7.43(s,lH), 7.49(s,lH), 7.62(dd,lH), 8.40(s,lH) Compound 5-98 δ 1.06(t,3H),1.80-1.92 (m,2H), 2.01-2.04(m,4H), 2.57(brs,2H), 2.93(d,2H),3.97(t,2H), 4.18(dd52H),4.57(s,lH), 1306016 6.85(d,lH), 7.01(d,lH),7.1 l(s,lH),7.17(d,lH),7'35(dd,lH),8.40(s,lH) Compound 5-209 δ 1.5 7-l_63(m , 2H), 2.04-2.06 (m, 2H), 2.5 8 (brs, 2H), 3.07 (d, 2H), 4.17 (dd, 2H), 4.64 (s, lH), 5.27 (s, 2H), 6.60 (d, lH), 6. 98-7.09 (m53H), 7.24 (d-like, 2H), 7.32 (d, lH) 5 7.62 (dd, lH), 8.39 (s, lH)

Compound 5-104 δ 1.41 (t, lH), 1.59-1.66 (m, 2H), 1.77 (t, lH), 2.05 - 2.22 (m, 3H)) 2.60 (brs, 2H), 3.1 l (dd, 2H) ), 4.05(t,lH), 4.19(dd,2H), 4.29(dd,lH),4.66(s,lH),6.61(d,lH),7.05(d,lH),7.14(s,lH) , 7.23 (d-like, lH), 7.62 (dd, lH), 8.39 (s, lH) Compound 5-206 δ 0.92 (t, 3H), 1.42-1.47 (m, lH), 1.5 7-1.80 (m , 5H), 1.98-2.04 (m, 2H), 2.35 (brs, 2H), 3.55 (dd, 2H), 3.93 (t, 2H), 4.08 (d, 2H), 4.48 (t, lH), 6.62 ( d, lH), 6.99 (d, lH), 7.09 (s, l H), 7.12 (d, lH), 7.62 (dd, lH), 8.42 (s, lH) Compound 7-103 δ 0.3 5-0.40 ( m,2H),0· 6 l-0.67(m,2H),1,24-1.36 (m,lH),1.45-1.51 (m,lH),1.57-1.63 (m,2H),1.67- 178 1306016 1.88 (m, lH), 2.18-2.31 (m, 4H), 3.25 (d, 2H), - 3.91 (d, 2H), 4.46 (d, 2H), 4.62 (s, lH), 6.66 (d, lH) ), 7.02 (d, lH), 7.1 〆 2 (s, lH), 7.18 (d, lH), 7.63 (dd, lH), 8.42 (s, lH) Compound 2-130 δ 1.31 (d, 3H), 2.00-2.22(m,6H), 2.40-2.50(m,2H), 3.45(s,3H),3.72-3.81(m,lH),3.88-3.93(m,lH),4.01-4.06(m,lH ), 4.56-4.61 (m+brs, 3H), 6.56 (d, lH), ^ 6.77 (d, lH), 7.10 (s, lH), 7.17 (d, lH), 7.61 (dd, lH), 8.40 (s,lH) Compound 1-98 δ 1.05(t,3H ), 1.13 (d, 3H), 1.71-1.91 (m, 4H), 2.05- 2.15 (m, 2H), 3.00 (dd, lH), 3.22-3.30 (m, lH), 3.98 (t, 2H), 4.10- 4.24 (m, 2H), 6.67 (d, lH), 6.98 (d, lH), 7.10 (d, lH) 57.16 (d, lH), 7.61 (dd, lH), 8.39 (s, lH) ^ Compound 5-118 δ 0.36(q, 2H), 0.63 (q, 2H), 1.19-1.31 (m, lH), 1.55-1.63 (m, 2H), 2.07 (brt, 2H), 2.5 7 (brs, 2H) ), 3.07 (d, 2H), 3.87 (d, 2H), 4.1 7 (dd, 2H), 4.63 (s, lH), 6.5 9 (d+q, 2H), 6.99-7.03 (m, 3H), 7.61(dd,lH),8.3 9(s,lH) Compound 8-4 δ 1.40-1.5 6(m,lH),1.75-1.86(m,3H),1.91-2.05 179 1306016 (m,2H),2.61 (brs, 2H), 3.40 (dd, 2H), 4.16 (d, 2H), 4.56 (t, lH), 5.81 (s, lH), 6.62 (d, lH), 6.91 (d, lH), 7.13 ( d, lH), 7.19 (s, lH), 7.63 (dd, 1H), 8.42 (s, 1H) Compound 2-90 δ 1.08 (t, 3H), 1.81-1.93 (m, 2H), 1.97-2.09 ( m,4H), 2.16- 2.24(m,2H), 2.40-2.46(m,2H), 2.98(s53H), 3.97(t,2H),4.48(brs,2H),4.59(t,lH),6.5 7(d,lH),6.77(d,lH),7.07(s,lH),7.14(d,lH),7.51(dd,lH),8.07(s,lH) Compound 2-167 δ 0.98 (t, 3H), 1.42 (t, 3H), 1.67-1.75 (m, 2H), 2.01-2.23 (m, 6H) 52.42 (d, 2H), 2.87-2.97 (m, 2H), 4.28-4.35 ( m, 2H), 4.5 7 (brs, 2H), 4.62 (t, lH), 6.56 (d, lH), 6.84 (d, lH), 7.39 (d, lH), 7. 62 (dd, lH), 7.70 ( s,lH),8.41(s,lH)

</ RTI> <RTIgt; 3.90-3.99(m,2H),4.08(q,2H), 4.13-4.3 8(m,2H),4.77(brs,lH), 6.71(d,lH), 7.06 (s,lH),7.09(d , lH), 7.16 (d, lH), 7.60 (dd, lH), 8.37 (s, lH) Compound 5-93 δ 1.06 (t, 3H), 1.63-1.69 (m, 2H), 1.74-1.88 (m , 2H), 2.00-

180 1306016 2.02 (m, 2H), 2.55 (brs, 2H), 3.01 (d, 2H), 4.00 (t, 2H), 4.07-, 4.16 (m, 2H), 4.3 8 (s, 2H), 4.5 9 (s, lH), 〆 6.5 9 (d, lH), 7.01 (d, lH), 7.10 (s, lH), 7.13 (d, lH), 7.50 (dd, lH), 8. 12 (s, lH) Compound 2-81 δ 1.09(t,3H), 1·84-2.2 l(m,8H), 2.40-2.43(m,2H), 3.97(t,2H),4.5 6-4.62(brm,3H) , 6.5 6 (d, lH), 6.73 (d, lH), reference 7.08 (s, lH), 7.23 (m, lH), 7.62 (dd, lH), 8.41 (s, lH) Compound 2-67 5 2.00 -2.21 (m, 4H), 2.28-2.3 5 (m, 4H), 4.5 9 (brs, 2H), 4.66 (t, lH), 6.5 8 (d, lH), 6.88 (d, lH), 7.63 ( Dd,lH), 7.74(d,lH), 7.86(s,lH),8.41(s,lH) Compound 5-99 # ' δ 1.06(t,3H),1.5 8-1.63(m,2H) , 1.65-1.8 9 (m, 2H), 2.02 - 2.04 (m, 2H), 2.57 (brs, 2H), 3.06 (d, 2H), 4.00 (t, 2H), 4.16 (d, 2H), 4.62 ( s,lH),6.5 7(t,lH),6.63 (d,lH),7.01(d,lH),7.1 l(s,lH),7.17(d,lH), 7.60(dd,lH),8.24 (s, 1H) Compound 5-103 δ 1.04 (t, 3H), 1.57-1.64 (m, 2H), 1.77-1.88 (m, 2H), 1.96-

181 1306016 2.04 (m, 2H), 2.5 8 (brs, 2H), 3.13 ^ (d, 2H), 3.91 (t, 2H), 4.17 (d, 2H), 4.52 (s, lH), 6.61 (d, lH), 6.63 (d, 〆lH), 6.75 (s-like, 2H), 7.63 (dd, lH), 8.40 (s, lH) Compound 5-101 (5 1.06 (t, 3H), 1.47 - 1.67 ( m, 3H), 1.79-1.9 1 (m, 2H), 2.01-2.04 (m, 2H), 2.5 6 (brs, 2H), 3.03 (d, 2H), 3.97 (t, 2H), 4.09 (dd, 2H), 4.57 (brs, 2H), 4.60 (s, lH), 6.61 (d, lH), ^ 7.01 (d, lH), 7.1 l (s, lH), 7.17 (d, lH), 7.52 (dd , lH), 8.14 (s, lH) Formulation Example [Insecticide • Acaricide] The following are examples of several compositions of the present invention, however, additives

The addition ratio is not limited to the examples, and can be varied within a wide range. The "parts" in the formulation examples mean "parts by weight". Formulation Example 1 Hydrating agent The compound of the present invention, 40 parts of Shixiazao soil, 53 parts of sulphate, barium sulfate, 4 parts of sulphonic acid naphthylate, 3 parts, the above components are uniformly mixed and pulverized into a fine powder to obtain an active ingredient of 40 % hydrating agent. Formulation Example 2 Emulsion Compound of the invention 30 parts Xylene 33 parts 182 1306016

Dimethylguanamine Polyoxyethylene acetophenone Ethyl ether The above ingredients are uniformly mixed and the emulsion is dissolved. Formulation Example 3 Powder 3 parts 7 parts To give an active ingredient of 30% of the compound of the present invention talc polyoxyethylene alkyl allyl ether

The above ingredients were uniformly mixed and pulverized to a powder of 10%. Formulation Example 4 Granules Fine powder, the active ingredient is

The compound of the present invention, 5 parts of clay, 73 parts of bentonite, 20 parts of dioctylsulfosylsodium sulphonate, 1 part of sodium phosphate, 1 part of the above components, the above ingredients are thoroughly pulverized and mixed, and after mixing with water, the granulation is dried to become an active ingredient of 5%. Granules. Formulation Example 5 Suspension Agent Compound of the present invention 1 〇 parts sodium lignin sulfonate 4 parts sodium dodecyl benzoate 1 part scutellaria gel 0.2 parts water 84.8 parts

183 j3〇6〇16 After the above components were mixed, the particles which were pulverized in wet shit to a particle size of 1 #m were used as a suspension having an active ingredient of 10%. Next, a test example in which the compound (4) of the present invention is used as various active ingredients for killing worms will be described. Test Example 1 for the efficacy of Tetranychusurticae K〇ch

In the 3 pots, the beans were sown 7~1 发芽 after germination, and after the first leaves were inoculated with 17 of the adult larvae resistant to the organophosphorus agent, according to the above-mentioned pharmaceutical example 1 In the formulation of the hydrating agent, the drug solution was diluted with water to make the compound concentration of 125 ppm and then sprinkled. The temperature was 25 ° C and the humidity was 65%. In the greenhouse, the rate of killing insects was checked after 3 days. The test was repeated twice. As a result, the following compounds have a 100% insecticidal rate. 1-8' 1-9' 1-1〇' 1-13' 1-15' 1-16' 1-17' 1-18' 1-19' 1-22, 1-23, 1-27, 1 -29, 1-44, 1-45, 1, 46, 1-47, 1-48, 1-49, 1-54, 1-57, 1_59, 1-63, 1-66, 1-67, 1 -69, 1-71, 1-72, 1-73, 1-74, 1-75, 1-76, 1-79, 1-80, 1-81, 1-82, 1' 88, 1- 89 , 90, 1-91, 1-92, 1-93, 1-94, 1 97' 1- 98' 1〇〇' I-101' 1_ 102' 1-i〇5'i- 108' 114, 1-115, 1_117, 1_118, 1-133, 1-136, 1-139, 1-140, 1-142, 1-143, 1-147, 1-150, 1-153, 1-163, 1- 172, 1- 173, 1_ 174, 1-179, 1-180, 1-181 ' 1-182 ' 1-183 ' 1-184 ' 1-186 ' 1-187 ' 1-188 ' 1-189 ' 1-190' 1-191' 1-192 2-51, 2-54, 2-57, 2-58, 2-59, 2-60, 2-62, 184 1306016 2-77, 2-78, 2-8 Bu 2-82, 2-83, 2-84, 2-85, 2-86, 2-89, Μ 2-93, 2-95 ' 2-96, 2-97, 2-98, 2 -100, 2-102, 2-105, 2-111, 2-112, 2-115, 2-130, 2-138, 2-141, 2-143, 2-144, 2-145, 2-147 , 2-148, 2-150, 2-15, 2-152, 2.155, 2-157, 2-159, 2-160, 2-16, 2-165, 2-166, 2-168, 2-169, 2-171, 2-173, 2-174, 2-175, 2- 177, 2-178, 2-179, 2-18, 2-182, 2-183, 2-184, 2-186, 2-187, 2-190, 2-192, 2-193, 2-194, 2-195, 2-196, 2-198, 2-199, 2-200, 2-2CH, 2-203, 2-205, 2-20 8, 2-209 '2-210 ' 2-21 Bu 2 -212 ' 2-213, 2-220 ' 2-221 ' 2-223, 2-225, 2-226, 2-227, 2-230, 2-232, 2-23 3, 2-234, 2- 235, 2-236, 2-237, 2-239, 2-240, 2-245, 2-246, 2-247, 2-248, 2-249, 2-250 5- 22, 5-32 ' 5 - 38 &gt; 5- 69, 5-70 ' 5- 72, 5-73,

5- 75, 5-89 ' 5- 90, 5-96 ' 5- 97 ' 5- 98 ' 5- 99, 5 -100 &gt; 5- 102 ' 5- 104 ' 5- 105 ' 5- 106 , 5 - 110' 5-111 ' 5- 114' 5- 116' 5- 118, 5-120, 5-121 ' 5- 124, 5- 125 , 5- 126 , 5- 127 , 5- 128 ' 5- 129 , 5_ 130 , 5 -134 , 5- 138 , 5- 139 , 5- 147 , 5- 149 , 5- 161 , 5-162 ' 5- 163 ' 5- 164, 5-174, 5-175, 5- 176, 5_ 177, 5- 182, 5- 183, 5- 184, 5- 190, 5- 191, 5- 198, 5 -199, 5- 200 ' 5-203 ' 5-204 ' 5-205 ' 5 -206 ' 5-207 ' 5-208 , 5-209 , 5-210 , 5-211 , 5-212 , 5-213 , 5-214 , 5-215 , 5-217 , 5-218 , 5-220 ' 5-222 ' 5-223, 5-224, 5-225, 5-227, 5-229, 5-230, 5-23 Bu 5-232, 5-233, 5-234, 5-235, 5 -236, 1306016

-124, 5-149, 5-162, 5-174 ' 5- 175, 5-177'5-190, 5-203, 5-215, 5-217, 5-218, 5-220, 5-222 , 5-224, 5-225, 5-227, 5-229, 5-230, 5-233, 5-234, 5-236, 5-237, 5-239, 5-243, 5-245, 5 -256, 5-257, 5-259, 5-260, 5-261, 5-262 7-82, 7-100, 7-103 Test Example 3 Commercially available artificial feed for the efficacy of Mythimna separate (Insecta LFS, manufactured by Japan Agribusiness) 〇.2ml 0&quot; Filled in plastic test tube (capacity 1.4ml) for use as a test feed. The drug was prepared as a 1% compound solution using DMSO (containing 0.5% tween 20), and a compound equivalent to ΙΟ/zg was dropped on the surface of the feed. Each of the test tubes was inoculated with 2 coatworms, 2 year old larvae, and sealed with a plastic cover. After 25X:, 5曰, check the insecticidal rate and food intake. The test was repeated twice. The insecticidal rate of the following compounds in this test was 1%, and the ratio of the food intake to the solvent control zone was 10% or less, which was effective.

1-8, 1-9, 1-13, 1-15, 1-17, 1-22, 1-23, 1-27, 1-39, 1-45, 1-46, 1-59, 1- 69, 1-72, 1-74, 1-75, 1-79, 1-80, 1-83, 1-95, 1-97, 1-981-100, 1-105, 1-108, 1- 114, 1-133 'Bu 140, 1-147, 1-153, 1-165, 1-166, 1-181, 1-182, 1-183, 1-184, 1-187, 1-189, 1 -190 2-21 ' 2-30 ' 2-51 ' 2-54 ' 2-57 ' 2-67 ' 2-82 ' 2-83 ' 2-94 ' 2-130 ' 2-138 ' 2-141 ' 2-143 ' 2-144 ' 2-148 ' 2-160 ' 2-161 ' 2-162, 2-166, 2-167, 2-169, 2-170, 2-171, 2-176, 2- 177, 2-1 8 Bu 2-182, 2-185, 2-193, 2-203, 2-204, 2-208, 2-211,

187 Γ306016 2-213,2-226 ' 2-23 3 ' 2-23 5,2-23 6,2-237 ' 2-23 8、2-23 9 '

2-240 ' 2-246 3-62 ' 3-131 5-22 , 5-73 , 5-75 , 5-89 , 5-90 , 5-96 , 5-97 , 5-105 , 5-110, 5-116, 5-120, 5-138, 5-147, 5-194, 5-147, 5-149, 5-174, 5-175, 5-176, 5-190, 5-210, 5- 212, 5-224, 5-225, 5-228 &gt; ' 5-237 &gt; 5-241 ' 5-242 ' 5-243 &gt; 5-244 ' 5-245 ' 5-246 , 5-256 , 5-259, 5-262, 5-265 6-82 7-82 ' 7-103 9-83 , 9-94

[Industrial Applicability I] The cyclic amine compound represented by the formula [I], a salt thereof or an oxide thereof has a good effect as an active ingredient of an insecticidal or bactericidal agent. [Simple description of the diagram] None [Main component symbol description] None 188

Claims (1)

1306016 X. Patent application scope: m v J ι One formula [i] % [wherein R3, R31, R4, R41, R5, R51, R6, R6i and R7 are each independently represented by a hydrogen atom, a Cw alkyl group, a Cy alkoxycarbonyl group or (:i 6 alkoxy group, R3 and R4) , or R5 and R6 may be bonded to form a saturated ring; when R3 and R4, or R5 and R6 are bonded together to form a saturated ring: R1 is a hydroxyl group, a halogen atom, a cyano group, a nitro group, a methyl group, There may be a Cu6 alkyl group of a substituent G1, a c2_6 alkenyl group, a C2-6 alkynyl group, a Cy haloalkyl group, a C2_6 haloalkenyl group, a (^.6 alkylcarbonyl group, a Cl_6 alkoxy group which may have a substituent G2, C , 6 halo-alkoxy, C 2_6 alkenyloxy, C 2-6 haloalkenyloxy, C 2.6 alkynyloxy, CN 6 ^alkylideneoxy, Cl-6 alkoxycarbonyloxy, Cl-6 An alkylthiocarbonyloxy group, an amine group which may have a substituent G3, a Cw alkylthio group, a Cl.6 haloalkylthio group, a Ci_6 alkylsulfuric acid group, a pyridylsulfuric acid group, a c^alkyl group Indeed, alkyl, .6 alkylsulfonyl, "alkylsulfonyloxy, C1_6-dentoalkylsulfonyloxy, heterocyclic group which may have a substituent G4 (containing an oxygen atom, a t atom) And a 5-membered ring of 6-membered ring of at least one of the sulfur atoms), or, the following formula: —OP(0)(OR8)SR9 189 1306016 I—Ο — A —C 〇2 — R10 [wherein R and R9 are each independently, indicating Cu appearance; γ ΐ, γ 2 and Υ 3 are independent of each other, representing an oxygen atom or a sulfur atom; A (including at least: an oxygen atom and at least one of a gas atom - a hetero atom: 6 members) Ring) heteropoly group, R1. Represents Ci 6 alkyl, C&quot; alkenyl. 2_6 alkynyl, &lt;: 6 alkyl group C1.6 alkoxy, Ci 6 functional group, or a substituent may be substituted for G (containing at least one selected from an oxygen atom, a nitrogen atom and a sulfur atom) a heterocyclic group of 5-membered ring to 6-membered ring; RU and Rl2 are each independently a hydrogen atom, a Cl-6 alkyl group, a C2-6 thin group or a C2_6 alkynyl group; and R13 and Rl4 are each independently represented C!·6 alkyl, RU and RM can be bonded to form a ring] 'R and R, and R5 and R6 are not bonded together to form a saturated ring 0 spear: R1 is a trans group, a cyano group, a C2.6 dilute group, a C2_6 alkynyl group, a 6-halogen compound group, a C2_6 haloalkenyl group, a Cw alkylcarbonyl group, a ci 6 oxy group which may have a substituent g2, G- 6 halo alkoxy, 〇2·6 diloxy. 2·6 haloenyloxy, c2 6-oxyl, alkylcarbonyloxy, Cl.6 alkoxycarbonyloxy, Cl-6alkylthiocarbonyloxy, alkylthio, Cl·6halane Thiothio group, Cl-6 alkyl sulfinylene group, alkyl sulfinylene group at CN6, Cw alkylsulfonyl group, Cw from alkylsulfonyl group, Cli fluorenyl fluorenyl group, Cw halogen group醯 醯, 可 190 1306016 phenyl group which may have a substituent G4, dihydrofurazan which may have a substituent G4, a furyl group which may have a substituent a, or the following formula: —〇P(〇K〇R8 ) SR9 —Y1C(=Y2)—Y3r8 一Ο—A [wherein, R8, R9 are as described above, Ri3 and; YR13 14 R may be bonded to form a ring] wherein m represents an integer of 0 or 1 to 5; R2 represents a halogen atom, a nitro group, q λp ^ ^ w indulgent ci-6 alkoxy group, cN6 halogen An alkyl group, which may have a substituent G4 (containing 5 members of a hetero atom selected from a ruthenium atom, a nitrogen atom, and a sulfur atom, ^ g: A, a 6-membered ring) heterocyclic group or C^ 6 Halane rolling base, k means 〇 or! An integer of ~4; X represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group; the surface is not a supergroup, c, .6 is an oxo group, and Ci6 may have a selected oxygen atom and a sulfur atom. At least one of the heteroatoms of the 5-membered ring to 6 members of the C3-6 cycloalkyl group; *Clear 4:2 represents the fluorescing group, the cyano group, the amine group U-oxo-x thiol group which may have a substituent G4,炫基Continuous thiol, Cw morphoxy, Ci-6 191 1306016 methoxy Cw alkoxy, C36 cycloalkyl or a halogen atom which may have a substituent or a C6.1Q aryl group of a 6 alkyl group; G3 represents C, -6 alkyl, Cw alkylcarbonyl or CV6 alkylsulfonyl; Q4 represents Cw alkyl or Cl-6 alkoxy; n represents a compound of 0 or 1], a salt of a compound of the formula [1] Or N-oxide. 2_ The compound of claim 1, wherein the substitution position of R2 is the 5th position on the pyridine ring. 3. A compound according to claim 1 or 2, wherein at least one of the substitution positions of Ri is the second position on the benzene ring. A pest control agent comprising a compound represented by the formula [丨], a salt of the compound of the formula or an N-oxide as an active ingredient, and is characterized in that: Wherein R1 is a hydroxyl group, a halogen atom, a cyano group, a nitro group, a decyl group, a Cm alkyl group which may have a substituent G1, an anthracene group, an alkenyl group, a C2.6 alkynyl group, a Cl-6 haloalkyl group, C2_6 haloalkenyl group, Cw alkylcarbonyl group, c-group oxy group which may have a substituent G2, cv6 halooxy group, c2-6 decyloxy group, c2_6 haloenyloxy group, c, £2-6 alkynyloxy group, Cw alkylcarbonyloxy, Cw alkoxycarbonyloxy, (: w alkylthiocarbonyloxy, amine group which may have a substituent G3, C, .6 alkylthio, cl6 192 1306016 alkyl sulphur Base, c1-6 alkylsulfuric acid, cv6 ialkylsulfinyl, decylsulfonyl 'Cw haloalkylsulfonyl, Cw alkylsulfonyloxy, c ii alkylsulfonate An oxy group, a heterocyclic group which may have a substituent G4 (having a 5-membered ring to a 6-membered ring selected from at least one of a gas atom, a nitrogen atom and a sulfur atom), or 'the following formula. —0P(0)(0R8)SR9 —Y1C(=Y2)— y3r8 —Ο—A -co2~ri〇 l丹1r, κο和^一今,, 丨, I 1-6 疋 ·, · Y 1, γ2 and their respective independent 'epoxy atoms or sulfur atoms; Α is a substituent G4 ^ contains oxygen At least one of the atom and the nitrogen atom - a 5-membered ring of a hetero atom; a heterocyclic group; Ri 〇 Γ Γ Γ 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表 表The group C丨·6 alkoxy, 忐栌a, and ten τ are G4 (containing a penta] group or a substituent capable of substituting a 5-member ring selected from an oxygen atom, a nitrogen atom and a sulfur atom. +, 杂 main ^ heterochlorinated atom, c V base: ; ... 12 are independent, independent, 亍 c V or even. 2_6 fast base; R13 algebra: 6 6 Rl4 can be bonded to form a ring The shape of the sample m is not 0 or an integer of 1 to 5; R2 represents a south atom, a nitro group, a c haloalkyl group, a substituent W alkyl group, a Ck6 alkoxy group, and a CN6 i group derived from an oxygen atom. , nitrogen atom and sulfur 193 1306016 at least one of the heteroatoms of the 5 member ring ~ 6 member ring) heterocyclic group or hydrazine alkoxy group, k represents 0 or an integer of 1 to 4; K6 曰 independent, represents hydrogen Atom, Cw alkyl, Cw alkoxycarbonyl or Ci δ atmosphere R3 and R4, or R5 and R6 may be bonded together to form a saturated ring; soil X represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group; G1 represents a hydroxyl group, a Cy alkoxycarbonyl group, Ci 6 alkoxy, 1 Λτ 1'6 /&gt; 〇ST group c,·6 alkoxy, the substituent G4 may be selected from at least one of an oxygen atom, an electric, a gas atom, and a sulfur atom. a 5-membered ring of a hetero atom, a 6-membered ring, a C3-6 cycloalkyl group; hydrazine, or G2 represents a hydroxy group, a cyano group, an amine group which may have a substituent G4, a Ci6 alkoxycarbonyl group, a Cw alkylthio group, C16 alkylsulfonyl, 6 alkoxy, Ci 6 alkoxy C 6 alkoxy, 〇 3 · 6 cycloalkyl or C61 which may have a halogen atom of a substituent or a C!-6 alkyl group. Aryl; G3 represents Cw alkyl, C| 6 alkylcarbonyl or q 6 alkylsulfonyl; G 4 represents Cw alkyl or Cl 6 alkoxy; n represents 0 or 1]. Into the insecticide, a compound represented by the formula [1], a salt of the compound represented by the formula [丨] or a cerium-oxide as an active ingredient is characterized in that: 194 1306016 R1 m A [i] Wherein R1 is a trans group, a halogen atom, a cyano group, a nitro group, a bromo group, a CV6 alkyl group which may have a substituent G, a C2-6 alkenyl group, a C2-6 alkynyl group, a C, a 6-dentate alkyl group , C2.6 haloalkenyl group, Cw alkylcarbonyl group, Cw alkoxy group which may have a substituent G2, CV6 haloalkoxy group, C2.6 alkenyloxy group, (: 2-6 haloenyloxy group, C2.6 alkyne oxide , Cw alkylcarbonyloxy, (^.6 alkoxycarbonyloxy, (6. 6 alkylthiocarbonyloxy, amine which may have a substituent G3, Cw alkylthio, haloalkyl sulfide) , Cw alkyl sulfinyl 'Cm haloalkyl sulfinyl, c 1-6 alkyl sulfonyl, Cw haloalkyl sulfonyl, Ci 6 alkyl sulfonyloxy, C! halane a sulfonyloxy group, a heterocyclic group which may have a substituent G4 (containing an oxygen source) a 5-membered ring of at least one of a hetero atom, a nitrogen atom, and a sulfur atom to a 6-membered ring /, ' or, the following formula: —〇P(0)(OR8)SR9 -Y^C^Y2)— y3R8 —Ο ——A —C09—R 10 Calving / V4 R13 195 1306016 [Where, R8 and R9 are each of the ancient masters - unveiled 'not C ^ Α β Y1 &gt; V2 » γ3 are independent, table h.6 alkyl, γ Υ and state of oxygen a heterocyclic group of an atom and a ring; R10〇矣 Ρ 5 ring of a hetero atom~6 C alkyl C ^ ^ not W alkyl, C 2 · 6 alkenyl, C 2-6 alkynyl, 1 G4 (Human 1, Cl. 6 haloalkyl) or may have a substituent to replace two people 3! Oxygen atom, nitrogen atom and at least one of the sulfur atoms - 5 members of the jade clothing ~ 6 members of the net eve, robbery sweet a heterocyclic group; R11 and R12 are each independently, and are a C6 group, a C2-6 group or a C2_6 alkynyl group; Rl3 and Rl4 are each independently a '1', and R13 and R14 are available. The bond forms a ring-formed one of the substituents, m represents an integer of 〇 or id; R2 represents a dentate atom, a nitro group, a Ci6 alkyl group, a k alkoxy group, a c&quot; functional group, and may be substituted a heterocyclic group of the group G4 (containing an oxygen atom, a nitrogen atom and a sulfur atom: at least - a hetero atom &lt; 5 M ring to a 6-membered ring) or a c-halomethoxy group, and k represents hydrazine or 1 to 4 An integer representing a hydrogen atom, a Cr. 6 alkyl group, a Cl 6 alkyloxy group or a Ci 6 alkoxy group, R 3 and R 4 ' or R 5 and R 6 may be bonded together to form a saturated ring; X represents an oxygen atom, a sulfur atom, a sulfur-containing or a hydrazine group, (1) represents a hydroxyl group, a Cw alkoxycarbonyl group, a Ci. 6 alkoxy group, a Ci 6 alkoxy group Cw alkoxy group, a substituent G4 may be selected from an oxygen atom, a heterocyclic group of a 5-membered ring of at least one of a hetero atom and a sulfur atom, or a C3.6 cycloalkyl group; G2 represents a hydroxyl group, a cyano group, an amine group which may have a substituent G4, and a hydrogen sulfide of Ci6 Base group, Cw burn Mercapto, Cw Hyun group brewing group, c1-6 its oxygen-hyun, c 196 1306016 burnt milk-based C! .G burnt milk group, C3 · 6 burning may have a substituent group or atom or voxel _ cv6 alkyl of Cw. Aryl; G3 represents Cw alkyl, Cw alkylcarbonyl or Cw alkylsulfonyl; G4 represents Cw alkyl or CV6 alkoxy; η represents 0 or 1]. 6. A smoldering agent comprising a compound represented by the formula [1], a salt of the compound represented by the formula [1] or a cerium-oxide as an active ingredient, characterized in that: [I] [wherein R1 is a trans group, a halogen atom, a cyano group, a nitro group, a methoxy group, a C 丨·6 alkyl group which may have a substituent G1, a Cw alkenyl group, a CM alkynyl group, and a Ci 6 tooth-burning Base, C _6 _ a dilute group, a C1-6 alkyl group, a c 1-6 alkoxy group, a Cw haloalkoxy group, a c2-6 alkenyloxy group, a c2-6 alkenyloxy group which may have a substituent g2 , c 2-6 alkynyloxy, Cw alkylcarbonyloxy, C 6 alkoxycarbonyloxy, ci 6 alkylthioloxy group, amine group which may have substituent G3, Cw alkylthio group, Cl .6 dentate thiol, Cw alkyl sulfinylene, Cl-6 alkyl sulfinyl, c 1-6 alkyl sulfonyl, Cw _ alkyl sulfonyl, Ci 6 alkyl sulfonate a decyloxy group, a c 1-6 haloalkylsulfonyloxy group, a heterocyclic group which may have a substituent G4 (a 5-membered ring containing at least one of a hetero atom selected from an oxygen atom, a nitrogen atom and a sulfur atom) Ring or, the following formula: 197 : 1306016 — 〇 P (〇) (OR *) SR9 — Y, C ( = Y2) — γ3^8 ~ O a A — C02 — R10 Η», 11 , R 12 [, 11 and 11 are independent, indicating 〇: 1.6 alkyl; ¥ 1, ¥ 2 and Table 7 ^ oxygen atom or sulfur atom '· A is a substituent G4 (3 optionally from oxygen atom and nitrogen source Zhongxuanyuan Qianzhongzhi/one of the heteroatoms of the 5-membered ring~6 members of the heterocyclic group; R丨〇 represents not C丨.6 alkyl, C2-6 alkenyl, C2_6 alkynyl, K6 a C1-6 alkoxy group, a C 忐俨萁, a 丄!-6 bai group or a substituent which may be substituted with G (3 optionally from an oxygen atom, a nitrogen atom and at least one of a sulfur atom) Atomic 5-membered ring ~ 6-membered ring) heterocyclic group; R11 gas m1 ο Into each other, is a ruthenium atom, a k-alkyl group, a c2 6-dilth group or a C2 6-block group; R13 and independently, indicating C, ^ M, TD 13 VL Τ» 1 4 Generation A - The one of the 本 形成 形成 ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] ] , q halogen group, may have replaced it...々,八士α土卜6 has a substituent G4 (containing at least one of the atoms selected from the oxygen atom, the atomic sgTia 虱 atom and the sulphur hetero atom) ~6 member ring) heterohaloalkyl milk base, k-table 〇 or an integer of 1 to 4; soil 3 b 6 R, R, R 4 , r 41 , r 5 , r 51 , R 6 , and R 7 represent a hydrogen atom, c ^ A r ^ &amp; each independently 'M alkyl, Ci_6 alkoxy The carbonyl group or c R and R, or R 5 and r 6 may be 1-6 calcined, and R may be bonded together to form a saturated ring; : 1306016 χ represents an oxygen atom, a sulfur atom, a sulfinylene group or a sulfonium group. G1 represents a hydroxyl group, a Cm alkoxycarbonyl group, a Cw alkoxy group, a Ci 6 alkoxy group, a 6 alkoxy group, a substituent G4, and at least one selected from the group consisting of an oxygen atom, a nitrogen atom and a sulfur atom. a 5-membered ring of a hetero atom to a 6-membered ring heterocyclic group, or a C 3-6 cycloalkyl group; G2 represents a hydroxyl group, a cyano group, an amine group which may have a substituent G4, a ci e alkoxy group 'C! 6 alkylthio group, a Cw alkyl group, a Ci-6 alkoxy group, a decyloxy group. Cw alkoxy, &lt;:3-6 cycloalkyl or Cn which may have a halogen atom of a substituent or a C1-6 alkyl group. Aryl; G3 represents Cw alkyl, Cw alkylcarbonyl or Cm alkylsulfonyl; G4 represents Cw alkyl or Cu alkoxy; n represents 0 or 1]. XI. 囷: No 199