TW201204254A - Pesticidal 3-(aryloxy)azacycloalkanes - Google Patents

Abstract

Disclosed are compounds of Formula 1, including all stereoisomers, N-oxides, and salts thereof, wherein A1 is N or CR7; A2 is N or CR8; A3 is N or CR9; A4 is N or CR10; provided that not more than two of A1, A2, A3 and A4 are N; T is O, S(O)k or NR36; L is -C(R11)=C(R12)-, wherein the carbon atom bonded to R11 is also bonded to CR4R5 and the carbon atom bonded to R12 is also bonded to R6; or 1, 4-diphenylene optionally substituted with up to 4 substituents independently selected from R13; or -C(R34)(R35)-Z-, wherein the carbon atom bonded to R34 and R35 is also bonded to CR4R5 and Z is bonded to R6; Z is O, S(O)m, NR37 or CR38R39; R1 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with up to 5 substituents independently selected from R14; R6 is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with up to 5 substituents independently selected from R22; s is 1, 2 or 3; t is 1 or 2; provided that the sum of s and t is 2, 3 or 4; and R2, R3, R4, R5, R7, R8, R9, R10, R11, R12, R13, R14, R22, R34, R35, R36, R37, R38, R39, W, k, m and n are as defined in the disclosure. Also disclosed are compositions containing the compounds of Formula 1 and methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound or a composition of the invention.

Description

201204254 VI. Description of the Invention [Technical Fields of the Invention] The present invention relates to invertebrate pests of certain 3_^ animals; in the 'agronomic environment', prevention and control such as arthropods for achieving high yield of crop production 10 15 = important = vertebrate animals The pest's harm to the long-term storage can cause a significant drop in yield and thus an increase in consumption. In the forest, greenhouse agriculture, (four) W to find the cost of food and fiber products, livestock Λ 'Jian r more for this purpose of the commercial products, still: continue to be more efficient, less cost, less toxic, The need for a safer or novel compound with 2 sites of action. , the second CT patent publication No. 2G_5146 A1, the insecticide, the mollusk and the nematicidal compound = contains - directly bonded to the - aromatic ring or hetero-aromatic ring [mouth + well, . The 3((aryloxy)azepines of the present invention are not disclosed in the present disclosure. SUMMARY OF THE INVENTION 20 201204254 The present invention relates to compounds of formula 1 (including all stereoisomers), their N. oxides and (iv)' and compositions containing the same and their use for controlling invertebrate pests:

Wherein A1 is N or CR7; A2 is N or CR8; 10 A3 is N or CR9; A4 is N or CR10; and the restriction condition is not more than two of N1, A2, A3 and A4; T system , s(0)k or NR36; 15 L lc(RU)=c(Rl2)-, wherein the breaking atom bonded to R11 is also bonded to CR4R5, and the carbon atom bonded to R12 is also bonded to R6; Or optionally substituted with up to 4 independently selected substituents, 1,4-diexene. Go-c(r34)(r35)-z-, wherein the carbon bonded to R34 and R35 is 20 The subunit is also bonded to CR4R5' and the Z system is bonded to R6; anti', Z system Ο, s(0)m, NR37 or CR38R39; ° ' vv 201204254

Ri is a phenyl or 5- or 6-membered heteroaromatic ring optionally substituted with up to 5 substituents independently selected from R14; R2 hydrazine, thiol, Cl-C6, and Cl-C6 Base, C2-C6 dilute group, C2-C6 13⁄4 base, C2-C6 fast group, C3-C6 function fast group, C3-C7 ring base group, C4-C8 cyclodendyl group, C5-C7 cycloolefin a group, a Ci-Q alkoxy group, a C2-C6 alkoxyalkyl group, -CHO, C^WbR15, c(0)OR16, C(0)NR17R18, S(0)pR19 or S(O)2NR20R21; R3 is independently i, cyano, CH:4 alkyl or Ci-C:4 alkoxy; R4 is hydrazine or Ci_C4 ray; r5 is hydrazine or C1-C4 ray; R6 is selectively a phenyl or a 5- or 6-membered heteroaromatic ring substituted with up to 5 substituents independently selected from R22; r7, R8, R9 and R1G are independently oxime, halogen, cyano, nitro, OR23, NR24R25, C plant C6 alkyl, CH: 6 haloalkyl, C2-C6 alkenyl, C2-C6 | g alkenyl, C2-C6 alkynyl, C3-C6 haloalkynyl, C3-C7 cycloalkyl, C4-C8 Cycloalkylalkyl, C5-C7 cycloalkenyl, -CHO, C(W2)R26, C(〇)〇R27, C(0)NR28R29, S(0)qR3°, S(0)2NR28R29 or 0C ( 0) R31; or a selectively up to 5 independent choices a phenyl substituted with a substituent of R40 or a 5- or 6-membered heteroaromatic ring; or a R7 and R8, or R8 and R9, or a vicinal pair of R9 and R10 and a carbon to which they are coupled The atoms together form a fused 5 or 6 member aromatic or non

An S 8 aromatic ring which comprises a ring member selected from carbon atoms and up to 3 heteroatoms independently selected from N, fluorene and S; R and R 12 are independently hydrazine, halogen, Ci-Q alkyl or Ci-C2 Alkoxy; each of R13, R14, R22 and R4G is independently _, cyano, nitro, hydrazine R23, NR24R25, c "c6 alkyl, Q-c6 functional, c2-c6 alkenyl, c2- C6 alkenyl, c2-c6 alkynyl, c3—c6 haloalkynyl “Cs-C: 7 cycloalkyl, c4-c8 cycloalkylalkyl, C5-C7 cycloaliphatic, _CHO, c(w2)r26 , c(o)or27, C(0)NR28R29, s(0)qR30, S(0)2NR28R29 or 〇C(0)R31; R and R are independently Q-C6 alkyl, Ci-C6 halogen fluorenyl , C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, c3-c6 haloalkynyl, C^C7 cycloalkyl, C4-Cs cycloalkylalkyl or C5-C7 cycloalkenyl; Or optionally up to 3 independently selected from the group consisting of halogen, cyano, nitro, hydrazine R23, NR24R25, Ci_C4 hexyl, (VC4 alkenyl, q-C4 alkynyl, Ci-C4 haloalkyl, C2-C26 Alkoxyalkyl, c2-C4 haloalkenyl, -CHO, C(W2)R26 > C(〇)〇R27. C(0)NR28R29' S(0)qR30 . S(〇)2NR28r29 and 0C( 0) a phenyl group substituted with a substituent of R31; each R and R20 Is independently H, c broad Q alkyl, Ci_C6 from alkyl, C2 - 〇6 dilute 'c2-c6 _ alkenyl, c2-c6 alkynyl, 3 6 _ block, C3-C7 cycloalkyl, QQ Ring-activated alumina or C5 i-based; or optionally up to 3 independently selected from 4, cyano, nitro, OR23, NR24R25, 201204254 Q-C4 alkyl, c2-c4 alkenyl, c2 -C4 alkynyl, Ci-C4 haloalkyl, Cz-C: 6 alkoxyalkyl, C2_C4 haloalkenyl, • CHO, C(W2)R26, C(〇)〇R27, C(0)NR28R29, a phenyl group substituted with a substituent of S(0)qR3Q, S(0)2NR28R29 and 〇c(〇)R3i; each R18, R2i, r24 and r- is independently H, c-wide Q-alkyl, c2-c6 Alkenyl or c2-c6 alkynyl; each R 9 , R 26 , R 2 W 〇 is independently c c6 alkyl or c "c 6 haloalkyl; each R and R 31 are independently H, c widely C6 alkyl or C" C6 functional base; each R, R and R37 is independently H, c wide c6 alkyl, c (〇) R32 or C (〇) 〇 R33; 15 each R and 尺 32 are independently H'CrC6 alkyl, Q-C6 sister group, c2-c6 base, c2-c6 haloalkenyl, c2_c6 alkynyl, =—C6 alkynyl, C3~~c7 cycloalkyl, c4-c8 cycloalkylalkyl or Cs-C :7 cycloalkenyl; each R is independently a Cr_C6 alkyl group, a secret group c2-C6, group, C2-C6 _ group, c2_c6 alkynyl, c3_c6 tooth alkyne i, C3—C7 cyclodextyl, c4-c8 cycloalkylalkyl or c5-c7 cycloalkenyl; r34 H C wide Cm p 4 condition base, Cr~C2S alkyl group, C2-C4 alkenyl group, R35 system 2 with 1: Cl'C4 alkoxy group or cyano group; R38 system h, 〇h, halogen tone p-circle, ( Vc2 alkyl or Ci-c2 alkoxy;

S 10 25 201204254

R39 is selected from the group consisting of hydrazine, cyano and Cl_C2 alkyl, and when R38 is halogen, then R is additionally selected from halogen; or R and R together with the carbon atom to which R38 and R39 are attached represent a carbonyl moiety; 〇 or S; wl is 〇 or s; each W2 is independently 〇 or s; k is 0, 1 or 2; 10 m is 〇, 1 or 2; n is an integer from 0 to 5; Ρ is 0, 1 or 2; each q series is independently 〇, 1 or 2; s is 1, 2 or 3; and t is 1 or 2; 15 The limiting condition is the sum of s and t, 2, 3 or 4. More specifically, the present invention relates to a compound selected from the group consisting of hydrazine compounds, N-oxides thereof or salts thereof.八20 The present invention also provides a composition comprising a compound of formula i, an N-oxide thereof or a salt thereof (ie, having a biologically effective amount) and at least a surfactant selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent The group, 'and other groups & In an embodiment, the present invention also provides a composition for controlling invertebrate harmful red, comprising a compound of the formula, preferably an N-oxide or a salt thereof, and at least one selected from the group consisting of a surfactant, a solid diluent And the group of __ _ its domain, the composition selectively further comprises at least one other biologically active compound or agent. 25 201204254

The present invention further provides a spray composition for controlling a compound comprising Formula 1. Insect _+, U, +, substance, N-oxide or a salt thereof or a slave composition and a face agent. The present invention provides a compound of the formula 1, a N-oxide or a salt thereof, or a composition of the above specific embodiment, one or more food materials, An attractant and a humectant as appropriate. The present invention further provides a capture device for controlling invertebrate pests, which comprises a shell and a shell suitable for (4) the feeding composition, wherein the shell has at least one opening, the size of the opening The invertebrate pest is allowed to pass through the opening so that the invertebrate pest can approach the bait composition from a location external to the outer casing, and wherein the outer casing is further adapted to be placed at a potential or known activity site for the invertebrate pest Or nearby. 20 The present invention provides a method of controlling an invertebrate pest comprising comprising a biologically effective amount of a compound of the formula, an N-oxide thereof, or a salt thereof (e.g., a composition described herein) and the invertebrate pest Or contact with the environment. The invention also relates to a method wherein a composition is contacted with the invertebrate pest or an environment thereof, the composition comprising a compound of the formula, an N-oxide thereof or a salt thereof (ie, having biological effectiveness) and at least one Other ingredients selected from the group consisting of surfactants, solid diluents, and liquid diluents, which selectively advance other biologically active compounds or agents comprising at least one biologically effective amount. The invention also provides a protection The method of seed or the exemption of invertebrate pests from plants grown by them' contains the seed with a lifetime

S 12 25 201204254 =· An effective amount of a compound of formula 1 or a bismuth-oxide or a salt thereof (e.g., a composition as described herein) is contacted. The invention also relates to treated seeds. The invention further provides a method of protecting an animal from parasitic pests of an invertebrate comprising administering a parasiticidally effective amount of a compound of formula 1 , a cerium-oxide or a salt thereof (eg, as described herein). Composition) to the animal. The invention also provides the use of a compound of formula 1, its bismuth-oxide or a salt thereof (e.g., a composition as described herein) for protecting an animal from invertebrate pests.实施方式方式 15 20 As used herein, the terms "including", "including", "having", "containing", "characterized" or any other variation/tune of the term are meant to encompass non-exclusive inclusions. 'And correct any restrictions expressed, such as 'inclusion-it parts list of compositions, mixtures, program items or equipment JiH secrets are clearly listed from the pieces or the composition, mixture, procedures, other provisions are available The components. If you want to use, or if you want to set up a patent, you will be asked to use the patent system, so that the reading of I will not include those other than the enumeration; the meeting will be made up of -. The word of the item, the word for the connection, the word, the word is limited to it; the other elements of the group r (4) in addition to the appearance of the 25th 201204254 conjunction "master 1 x Ge by · ·" (consisting Essentially)) used for materials, steps, specials, or groups other than those disclosed in the text, or 70 components, methods, or devices, provided that the equivalent materials include the steps and characteristics. The components, or components, do not substantially affect the basic and new features of the invention. The term "mainly composed of" resides in the middle ground between the package "$" and "..".立八右申人 defines an invention or its knives in an open-ended language such as "including" (unless otherwise stated). The statement should be interpreted as "mainly composed of" or "by _· "·Composed" describes the invention. "In addition," unless expressly stated to the contrary, "or" means an inclusive "or" rather than an exclusive "or". For example, any of the following cases satisfies condition A or B: A is true (or exists) and B is pseudo (or nonexistent), A is pseudo (or nonexistent) and B is true (or exists) and A and B All are true (or exist). "Additional articles" and "an" before and after the elements or components of the invention are intended to be non-limiting, the number of instances (i.e., the number of occurrences) of the element or component. Thus, the word "a" or "an" is intended to mean a singular or a singular singular singular singular singular. As the disclosure of the present invention, the term "invertebrate pest" includes arthropods, gastropods and nematodes that are of economic importance to pests. More than f' "invertebrate pests" represent arthropods and abdomen, and more specifically, "good axis pests" represent arthropods. The term "arthropod" includes Kun H. 蛛 壤 a a 马 马 马 马 马 马 马 。 。 。 。 。 。 。 。 。 。 。 。 。. S. "gastropods" include ox, milk I and other stalks. Terminology 201204254

10 15 20 "Nematodes" and "Nematodes" include members of the linear phylum, such as herbivorous nematodes. As disclosed herein, "control of invertebrate pests" means inhibiting the development of invertebrate pests (including death, reduced feeding, and/or disturbing mating), and the related description is a similar definition. The term "agronomy" means the production of field crops such as food and fiber, and includes the growth of the following crops, such as hubs, soybeans and other legumes, rice, cereals (eg wheat, oats, barley, rye, rice) , corn), leafy vegetables (eg lettuce, kale, and other cabbage crops), fruits and vegetables (eg, tomatoes, pepper, eggplant, cruciferous plants and melons), potatoes, sweet potatoes, grapes, cotton, trees Classes (eg, pear, stone and citrus), small fruits (berries, cherries) and other special crops (eg canola, hollyhock, olive). The term "non-agronomic" means other non-field crops such as horticultural crops (eg greenhouses, nurseries or decorative plants not grown in the field), residential, agricultural, commercial and industrial structures, turf ( For example, turf fields, pastures, golf courses, lawns, playgrounds, etc.), wood products, stored products, agriculture and forestry, vegetation management, public health (meaning), and animal health (eg, livestock, such as pets, livestock and Poultry, non-stock animals, such as wild animals) applications. "π" alkylating agent" means a compound 4 in which a carbon-containing radical is bonded to a cleavage group such as a _ compound or an I salt by a carbon atom by arranging a nucleophilic ride on a broken atom Let it go. Unless it is particularly strong, w η η M ' 逢 」 」 」 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不 不Replace free radicals. 25 201204254 In the above detailed description, the term 'hind base' is used either alone or in a compound such as "alkylthio" or "haloalkyl", including straight-chain or branched alkyl groups such as methyl. Ethyl, n-propyl, isopropyl or various butyl, pentyl or hexyl isomers. "Alkenyl" includes straight-chain or branched olefins such as ethyl, 1-propenyl, 2-propenyl and various butyric, pentenyl or hexenyl isomers. "Alkenyl" also includes polythene such as 1,2-propanyl and 2,4-hexanediyl. "Quick" includes straight-chain or branched acetylenes such as ethynyl, 1-propynyl, 2-propynyl and various butynyl, pentynyl or hexynyl isomers. "Alkynyl" also includes a moiety consisting of multiple reference bonds, such as 2,5-hexadiynyl. "Alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy and various butoxy, pentyloxy and hexyloxy isomers. "Alkoxyalkyl" means an alkyl group substituted with an alkoxy group. Examples of the "alkoxyalkyl group" include ch3och2-, ch3och2ch2-, CH3CH2OCH2-, CH3CH2CH2CH20CH2- and CH3CH2OCH2CH2 ""Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "cycloalkylalkyl" means substituted by a cycloalkyl group on the alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl and other cycloalkyl moieties bonded to a straight or branched alkyl group. The "cycloalkenyl group" includes a group such as a cyclopentene and a cyclohexene group and a group having a double bond or more, such as a 1,3- and 1,4-cyclohexadienyl group. The term "halogen" is used either alone or in a compound such as "alkyl" or in the context of an alkyl group such as r substituted by itself, including fluorine, gas, bromine or iodine. . Further, when used in a compound such as "haloalkyl" or in the description of "alkyl substituted by halogen, 201204254.", the alkyl group may be the same or not. The halogen atom is partially or completely replaced. "Haloalkyl" or "alkyl substituted with halogen" includes F3C-, C1CH2-, CF3CH2_ and CF3CC12-. The terms "ii alkoxy", "haloalkylthio", "haloalkenyl", "alkynyl" 5 and the like are defined similarly to the term "functional alkyl". Examples of "haloalkoxy" include 0 households 3-〇-, (:(:13(:出〇-, 1^?2(^2(:出〇- and €卩3(:112〇-. "halogen Examples of the alkylthio group include CC13S-, CF3S-, CC13CH2S_, and cich2ch2ch2s-. Examples of "haloalkynyl" include HC=CCHC1-, CF3CeC_, CCLCeC-, and FCH^CeCCH^·〇10 "Alkylcarbonyl" means one A straight or branched alkyl moiety bonded to the c(=o) moiety. Examples of "alkylcarbonyl" include ch3c(=o)-, ch3ch2ch2c(=o)., and (ch3)2chc(=o)-. Examples of "alkoxycarbonyl" include ch3oc(=o)-, ch3ch2oc(=o)-, ch3ch2ch2oc(=o)-, (ch3)2choc(=o)·, and various butoxy-15 or pentyloxycarbonyl The total number of carbon atoms in the substituent group is represented by the prefix "Ci-Cj", where i and j are numbers from 1 to 8. For example, c2 alkoxyalkyl represents CH3OCH2-; C3 alkoxyalkyl Representing, for example, CH3CH(OCH3)-, CH3〇CH2CH2- or CH3CH2OCH2-; and c4 alkoxyalkyl group, Table 20 shows various different alkyl group isomers, which are alkoxy groups containing a total of four carbon atoms. Group substitution, examples include CH3CH2CH2OCH2- and CH3CH2OCH2CH2-. When the compound is taken Substituent, and the substituent bears a subscript symbol indicating that the number of substituents may exceed 1, and the substituent (when it exceeds 1) is independently selected from the group consisting of the defined substituents, For example: (R3)n and η is 1, 2, 3, 4 or 5. When the group contains 17 201204254 ==::, ::, r8, r' then when the variant group is shown as being selectively connectable i to 2: not 2 generations. When can be u Na V where Γ can be 〇, two sets of two or two columns such as 'show! Even if the definition of the variable group does not mention setting, one or more positions In the case where "one atom on a group that is not substituted" is to be attached (10) according to any free price, hydrogen is used as a formula (for example, a substituent R丨 or R0) unless otherwise stated. Carbocycle: long system" stands for two or more _ rings. The term "fused ring heterodiforms = ring system" and - ring forms a monocyclic ring system. The term "2 to bicyclic system" means two fused rings. The ring system consisting of:, and then = 'the ring-ring can be saturated, partially unsaturated 15 20 Therefore: unless otherwise stated, each ring can be aromatic or non-operative H" means The atom of the ring or ring primary bond or its =; (for example, c (=0), c (= s), s (o) or s (0) 2). The slave ring", "carbocyclic compound" or "Carbocyclic" means a ring or ring system in which the atoms forming the ring backbone are selected from carbon only. Unless otherwise stated, a carbocyclic ring can be a saturated, partially unsaturated or fully unsaturated ring. When the -completely unsaturated carbon ring satisfies the shock rule (10)ekel, please le), then the ring is also called "aromatic ring". The term "heterocycle" or "heterocycle" means a ring or ring system wherein at least one of the atoms forming the ring backbone is not carbon, for example, nitrogen, oxygen or sulfur. Generally, a heterocyclic ring contains no more than 3 nitrogen atoms, no more than 2 oxygen atoms, and no more than 2 sulfur atoms. Unless otherwise indicated, a heterocyclic ring can be a saturated, partially unsaturated or fully unsaturated ring. Unless otherwise stated, 25 201204254 • · Fragrance. When a - completely unsaturated heterocyclic ring or an aromatic heterocyclic compound, the ring is also referred to as "heterois permeable to any available; ^ except = indicated" heterocycle and heterocyclic ring 5 are attached. Α or 虱, hunting by replacing the hydrogen on the carbon or nitrogen with the surface t = compound means that each ring atom is substantially in the same-flat r bean: the P orbit is perpendicular to the plane of the ring, and (4η + 2) π An electronic positive integer is associated with the loop to comply with the Shock Rule. Ϊ Ϊ ΐ ΐ / / / / / / / 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个 个2 The use of this article, the definition of the journal should apply to this article, unless the child's monthly treatment, I disregard the situation, can be used interchangeably with the phrase "replaced or not, = generation" or with the term "(un) replaced" . Unless otherwise stated, the radical group may have a substituent at each of the replaceable positions of the group and each substitution is independent of each other. ^ ro^Rl>R6'R7'R8'R9^Rl0^- 5^6 aryl, which, unless otherwise stated, may be attached to the remainder of Formula 1 via any available carbon ring atom or 7 nitrogen ring atom. As stated above, R1, R6, R, R, R9 or R10 may be, among other things, a phenyl group optionally selected from one or more substituent groups selected as defined in the Summary of the Invention. Substituted by a substituent. Examples of phenyl groups optionally substituted with one to five substituents are as shown by the formula iq in i, wherein 'system R 4, R22 or R40' are as defined in the Summary of the Invention, respectively, Ri, R, R7, R8, R9 or Ri〇' and r is an integer from 〇 to 5. 19 201204254 As noted above, Ruler 1, Ruler 6, Ruler 7, 118, 119 or 111() may be, among other things, a 5-inch or 6-membered heteroaryl ring, optionally with a maximum number of positions available. Substituted by a substituent, and the substituents are independently selected from the group consisting of groups defined by the disclosure of the invention (ie, 〇14 ο 22 τ^40\ „ or R respectively). Optionally one Examples of the 5- or 6-membered heteroaryl ring substituted with a plurality of substituents include the rings depicted in 1_2 to U-61 of the display 1, wherein RV is any of the redundant substitutions f' as defined in the Summary of the Invention. , R6, R7, R8, R9 or Rl° (meaning R, R or R40 respectively), and r is an integer from 〇 to 4, which is limited by the number of available positions on each ^^ group Since U-29, U-30, U-36, U-37, U-38, U-39, U-40, U-4, U-42 and U-43 y, there is a position available, these The r of the U group is limited to an integer of 〇 or 1, and 〇 means that the ϋ group is unsubstituted and hydrogen is present at a position denoted as (RV) r.

U]2 U-13 U-14 U-15

S 20 201204254

4 (Rv)r

N N-U-18

JJ (RV)r

4 (Rv)r Ο—N U-21

5 (RV)r YV S——N U-24 U-23 4 (Rv)r 丫VN—N 3 (RV)r 4 (Rv)rn N—N , t> (Rv)r U-26 U- 27 U-28 U-29 (Rv)rw if, N—N if N—N (Rv)r N—N U-31 U-32 U-33 U-34 (Rv)r:r 5—0 U- 20 (RV)r, 0 U-25 (RV)r U-30

U-36 U-37

N (RV)r U-39

(R )r (RV)r

(RV)r 'SN N-N7

(Rv)r

4 (RV)r

N // (rV n U-40 (Rv)r O N=N U-45 (Rv)r 6 U-46 6 (RV)r U-51 (RV)r N I N-N U-47

N=N U-48 (RV)r r^N 7 II U-53 person N”6

2 U-49

U-50 6 (Rv)r 'N

(RV)r 6 (R U-54 U-55 2 201204254

Although U-61 shows an Rv group in the structures 11.1 to U-61, it is worth noting that since these groups are optionally substituted, the groups are not required to be taken. It is worth noting that the nitrogen atom that needs to be replaced to fill its price is Η or rv. When the connection point between (RV) r and the ϋ group is not floating, (RV)r can be connected to the u group. Anything can be: being atomized. It is worth noting that the connected carbon or nitrogen groups on the U group pass through any of the available values on the U group; the r mains can be connected to the remainder of Equation 1 by replacing the hydrogen atoms. Q is some 1; groups can be replaced by only less than 4 rv* groups (example y called, and (d) to (10)) instead of two pairs of two 'two' and R8, or r8 and r9, Or r9 and Rl0 or 6 member aryl; group two carbons formed - fused 5 members 15 and R8, or ... 't / and R. , A2, A3, and 8 of 6 members are fused to the inclusion of A, and may be all unsaturated: 'one; = wide part -CH=CH-CH=CHn even examples include n > CH=N-CH=CH- ' s 22 201204254 -CH=CH-N=CH-, -CH=CH-CH=N-, -N=N-CH=N-, -N=CH-N=N -, -S-CH=CH-, -CH=CH-S-, -〇-CH=CH_, -CH=CH-0-, -〇-CH=N-, -N=CH-0-,- CHCH_, -CH=N-0-, -S-CH=N_, -N=CH_S_, _s raise CH, •CH=NS-, -(CH2)4-, -(CH2)3-, _ch= CH-CH2-, -CIVCHCH- '-OCH2CH2_, _CH2CH2〇, and _OCH2CH2〇- 'where the left-hand connection key corresponds to the ruler 7 and R8, or the left member of R8 and R9, or R9 and R1G, and the right-hand connection key corresponds to R7 and 10 15 • 20 R8, or R8 and R9, or R9 and f to the right. A neighbor that deserves special attention is α·Ι=(:Η-(:Η=(:Η-. In this technical field, there are various known methods for preparing aromatic heterocyclic rings and ring systems; extensive For review, see the eighth volume of comprehensive

Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees, ed., Pergamon Press, Oxford, 1984 and Twelfth

Comprehensive Heterocyclic Chemistry II, a. R Katritzky, C. W. Rees and E. F. V. Scriven, ed., pergamon Press, Oxford, 1996). The compounds of the invention may be present in one or more stereoisomers. Various stereoisomers include mirror image isomers, non-image isomers, atropisomers, and geometric isomers. It will be apparent to those skilled in the art that a stereoisomer may be more active and/or may exhibit beneficial properties when concentrated relative to other stereoisomers or when isolated from other stereoisomers. effect. Moreover, those skilled in the art know how to separate, concentrate and/or selectively prepare the stereoisomers. The compounds of the invention may exist as a mixture of stereoisomers, individual stereoisomers or optically active forms. 23 25 201204254 The compound of the present invention can be a conformational isomer of the present invention by the rotation limitation of the amine bond in Formula 1. The present invention encompasses conformational isomerizations: the inclusion of a perfusate rich in a conformational ampoule, which is richer than the other conformational isomers. The compound of the formula: l, its stereoisomer, tautomer, N-oxide j' usually exists in more than one form, and all the crystal forms and amorphous forms of the compound thus represented by the formula i. The amorphous package 15 and the glue_real_' also include examples such as solutions and refining. Crystalline forms include those which must exhibit a single-crystalline form and ... a mixture of polymorphs. (ie different crystal forms). The t-shaped body is a metamorphic form of a compound that can be crystallized into different crystal forms. These forms of intramolecular molecules have different arrangements and/or configurations. Heteropolymorphs may have the same chemical composition, and they may also differ in composition due to the presence or absence of other molecules of the co-crystal nucleus, which may be weakly or strongly bound in the crystal lattice. Polymorphic phases differ in handling, physical, and biological properties. Crystal shape, density, hardness, color, chemical stability, refining point, hygroscopicity, suspensibility, dissolution rate, and bioavailability. Those skilled in the art will appreciate that the polymorphism of the compound presented by <i can exhibit beneficial effects in combination with other rural or polymorphic forms of the same compound of Formula 1 (e.g., suitable for preparation) Formulations to improve bioavailability) Preparation or isolation of the polymorphs represented by formula i can be achieved by methods well known to those skilled in the art, for example, by using specific solvents and temperatures for crusting, Those skilled in the art will appreciate that not all nitrogen-containing compounds can form nitrogen oxides because the nitrogen atoms require an available orphan = 25 201204254 'electron pair to oxidize to oxides; skilled artisans in the field It will also be apparent that tertiary amines can form nitrogen oxides. The synthesis of N-oxo compounds for the preparation of heterocyclic and tertiary amines is well known to those skilled in the art, including peroxygenation with, for example, peroxyacetic acid and 3-phenylperoxybenzoic acid (MCPBA). An acid, hydrogen peroxide, an alkyl hydroperoxide such as t-butyl peroxy ruthenium, sodium perborate, and a dioxirane such as dimethyl dioxirane are used to oxidize the heterocyclic ring and the tertiary amine. Such methods for preparing N-oxides have been extensively described and reviewed in the literature, for example: TL Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. 10 v. Ley, Ed., Pergamon Press M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, AJ Boulton and A. McKillop, Eds., Pergamon Press; M_R. Grimmett and BRT Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, AR Katritzky, Ed., 15 Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291, AR Katritzky and A. J_ Boulton, Eds., Academic Press; and GWH Cheeseman and ESG Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, AR 2〇Katritzky and AJ Boulton, Eds” Academic Press. Derivatives derived from compounds of formula 1 when R2 is not H N-oxides are clearly the most stable. Those skilled in the art understand that because the salts of the compounds and their corresponding non-salt forms will be under environmental and physiological conditions. Yu Ping 25 balances the state, so the salt will share the biological effects of the non-salt form. Therefore, the salts of various compounds of formula 1 can be used to control invertebrate pests. The salts of the compounds of formula i 25 201204254 include those containing organic or inorganic acids. Acid addition salts, acids like hydrobromic acid, salt, nitric acid, squaric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, milk =, maleic acid, malonic acid, oxalic acid, propionic acid, water Acid, tartar 4-toluenesulfonic acid or valeric acid. When the formula 5 compound contains 5 (4) of acid D, the salt also contains those salts formed with money or inorganic bases, such as triethylamine or ammonia. , or guanamine, or a hydride, nitrogen oxide or carbonate of sodium, potassium, lithium, mom, or strontium. Accordingly, the present invention comprises a compound selected from the group consisting of a compound of the formula i, and an N-oxide thereof, which is biologically applicable. In the examples of the present invention, the following is included, and when the formula j is referred to, the N-oxide and its salt are included, and the term "a formula" is used unless otherwise specified in the examples. Otherwise contains the emphasized substituent definition. Present Embodiment 1. A compound of formula 1 wherein Αι is N. 15 Example 2. A compound of formula 1 wherein Αι is cR7. Example 3. - Compound of Formula 1 or Example i or 2 A2 is CR8. Compound Example 5. Example 6. Example 4. A compound of formula 1 or any of the examples 丨 to 3 wherein A3 is CR9. a compound of the formula 1 or any of the examples 丨 to 4 wherein A4 is CR10. Or a compound of any one of the above formulas, wherein R7, R8, R9 and each independently are H, dentate, green, schlossyl, 0R23, nr24r25, ca alkyl, Ci_C6 halogen, C2 -c6 alkenyl, c2_c6 halo, alkyne, c3-c6 haloalkynyl, c3-c7 cycloalkyl, c4-c8

S 26 25 201204254 Basis C5~C7 cycloalkenyl, _CH〇, c( 2 26 7 C(0)NR::R« . S(〇)qR30 .

Rl0(〇)R, or -R7 and R8, or R8 and R9, or R9 and the adjacent couples', and the carbon atoms to which they are attached, form a 5- or 6-membered aromatic or non-aromatic ring, Buns = ^1 more 3_ from the original of the N'^s. Example 7. The compound of Example 6, wherein r7 H , ^ is independent of Η, dentate, Cr~C4, and Cr_C4 Γ ' > elemental, C 2 -Q alkenyl, CrC 4 halo, Cr_C 4 alkynyl, 7 _ block, c 3 -c 6 cycloalkyl, Ci-C 4 alkoxy, dihalo alkoxy, CpCA thio , Cl_c4 _ thiol or chaotic group ' or -r7 and R8, or R8 and R9, or R9 & Rl 〇 15 25 ortho, together with the carbon atom to which they are attached form a fused or 6-membered aromatic Or a non-aromatic ring comprising a silver member selected from the group consisting of carbon = and up to 3 heteroatoms independently selected from N, 〇AS. Example 8. Compound of Formula 1 or any of Examples 1 to 7 = where R7, r8, r9 or R1G are independently separated (ie, a ring is not formed together), then R7, R8, R9 or Rl is independently ruthenium, dentate, Cl-c4 alkyl, Ci-C4 4 alkyl, C2-c4, c2-c4 haloal, c"i block, c3-c6 , a C-cardioxy' or a cyanyl-alkoxy group, a C1-C4 alkylthio group, a C1-C4*alkylthio group. 201204254 Example 9. A compound of embodiment 8, wherein R7, R8, R9 or When R1Q is isolated independently, the R7, R8, R9 or R1G is independently hydrazine, halogen or Q-C4 haloalkyl. Embodiment 10. The compound of the formula 1 or the compound of any of the examples 1 to 9 Wherein, when R7 is isolated, then R7 is a hydrazine or a halo group. Embodiment 11. A compound of embodiment 10, wherein when R7 is isolated, then R7 is hydrazine or F. Example 12. Compound of Example 11 Wherein, when R7 is isolated, then R7 is Η. ίο. Embodiment 13. The compound of Formula 1 or any one of Examples 1 to 12, wherein when R8 is separated, then R8 is hydrazine, halogen or halogen Example 14. One The compound of Embodiment 13 wherein, when R8 is isolated, R8 is H, halogen or C! fluoroalkyl (ie, fluoroindolyl, 15 includes CH2F, CHF2, and CF3). Example 15. Example 14 A compound wherein, when R8 is isolated, then R8 is hydrazine, halogen or CF3. Embodiment 16. The compound of embodiment 15, wherein when R8 is isolated, the beryllium J R8 is hydrazine, F, C1 or CF3. Embodiment 17. The compound of Embodiment 15, wherein when R8 is isolated, then R8 is halogen or CF3. Embodiment 18. The compound of Embodiment 17, wherein when R8 is isolated, then R8 is F, C1 or CF 3. Embodiment 19. A compound of Formula 1 or a compound of any one of Embodiments 1 to 18, wherein when R9 is isolated, R9 is a hydrazine, a halogen or a CrQ haloalkyl group.

S 28 201204254

Embodiment 20. The compound of Embodiment 19, wherein when R9 is isolated, then R9 is H, halogen or qfluoroalkyl (i.e., fluoromethyl). Embodiment 21. The compound of Embodiment 2 wherein, when R9 is separated, R9 is hydrazine, halogen or CF3. Embodiment 22. The compound of Embodiment 21, wherein when R9 is isolated, then R9 is hydrazine, C1 or CF3. Embodiment 23. A compound of the formula or a compound of any of Embodiments 1 to 22 wherein, when R10 is isolated, r1 is a hydrazine or a halide. 10. The compound of embodiment 23, wherein when R10 is separated, the R1G is Η or F. Embodiment 25. The compound of Embodiment 24, wherein when R10 is separated, then R1G is H. 15 Shell Example 26. A compound of formula 1 or any of embodiments 1 to 25, wherein the carbon of the R' and R8, or R8 and R9, or R9 f R's ortho' When the atoms together form a two-layered J coat, the ortho-couple is -CH=CH-CH=CH- (i.e., the fused ring system is benzo). 20 贝施^27· The compound of Formula 1 or the Examples 1 to 26=匕ί物' wherein -R7 and R8' or R8 and R9, or the adjacent couple of R9 are as described above with the carbon atom to which they are attached Together form a fused ring. Embodiment 28. The compound of the formula 1 or the compound of any of the examples 1 to 27 wherein the ortho to each of -R7 and R8, together with the carbon atom to which they are attached, form a fused ring. 29 25 201204254 Embodiment 29. A compound of the formula 1 or a compound of any one of the embodiments 1 to 27, wherein a argon of R8 and R9 together with the carbon atom to which they are attached forms a fused ring. Embodiment 30. A compound of Formula 1 or any one of Embodiments 1 to 27, wherein a argon of R9 and R10 together with the carbon atom to which they are attached forms a fused ring. Embodiment 31. A compound of Formula 1 or any one of Embodiments 1 to 25 wherein each R7, R8, r9 and R1 are separated (i.e., a fused defect is not formed together). Embodiment 32. A compound of Formula 1 or any one of Embodiments 1 to 31, wherein L is -CXRUfQR12)- 'wherein the carbon atom bonded to R11 is also bonded to CR4R5, and the bond is bonded to Rl2 The carbon atom is also bonded to R6; or, as the case may be, up to 4 oximes, independently substituted with a substituent selected from R13, 4-diphenyl. Example 33. One style! A compound or any one of embodiments 1 to 32 wherein L is a system. Embodiment 34. A compound of Formula 1 or a compound of any of Embodiments 1 to 33, wherein R11 and R12 are independently oxime, dentate or methyl. Embodiment 35. A compound of Embodiment 34 wherein R11 and R12 are independently hydrazine or methyl. Embodiment 36. A compound of Embodiment 35, wherein R11 and R12 are H 〇 Example 37. A compound of Formula 1 or any one of Examples 1 to 32 wherein L is optionally independently selected up to 4 independently. A 1,4-diphenyl group substituted with a substituent of Rl3.

S 30 201204254 Embodiment 38. A compound of Formula 1 or any one of Embodiments 1 to 31, wherein L is -C(R34)(R35)-Z-, wherein the carbon atom bonded to R34 and R35 It is also bonded to CR4R5, and the Z system is bonded to R6. 5. A compound of formula 1 or a compound of embodiments 1 to 31 or a compound of embodiment 38, wherein R34 is hydrazine or C]-C4 alkyl. Embodiment 40. The compound of Embodiment 39, wherein R34 is hydrazine or CrQ alkyl. </ RTI> The compound of embodiment 40, wherein R34 is hydrazine or methyl. Embodiment 42. The compound of Embodiment 41 wherein R34 is hydrazine. Embodiment 43. A compound of Formula 1 or a compound of Examples 1 to 31 or a compound of Examples 38 to 42 wherein R35 is hydrazine. 15 A compound of formula 1 or a compound of examples 1 to 31 or a compound of examples 38 to 43 wherein indole, S, NR37 or CR38R39 (i.e., m system 0). Embodiment 45. A compound of Embodiment 44 wherein Z is 0, S or NR37. The compound of Example 45, wherein Z is hydrazine or NR37. Embodiment 47. The compound of Embodiment 46, wherein Z is hydrazine. Embodiment 48. A compound of Formula 1 or any one of Embodiments 1 to 47, wherein R37 is hydrazine. A compound of formula 1 or a compound of any one of embodiments 1 to 48 wherein R38 and R39 are indole. 31. The compound of the formula 1 or the compound of any one of the embodiments 1 to 49, wherein when L contains a 1,4-linked phenyl group, the 1,4-linked phenyl group is selectively Substituted with up to 2 substituents independently selected from R13. 5. The compound of embodiment 50, wherein when L comprises a 1,4-linked phenyl group, the 1,4-diphenyl group is unsubstituted (except that it is bonded to C(R4) (R5) and R6). Embodiment 52. A compound of Formula 1 or any one of Embodiments 1 to 51, wherein each R13 is independently halogen or Ci-C4. Embodiment 53. The compound of Embodiment 52, wherein each R13 is independently dentate or sulfhydryl. Embodiment 54. A compound of Formula 1 or any one of Examples 1 to 53 wherein R1 is optionally substituted with up to 4 phenyl rings or 5 members independently substituted with a substituent selected from R14 or 6 members of the aromatic ring. Embodiment 55. The compound of Embodiment 54 wherein R1 is a phenyl or pyridine ring optionally substituted with up to 4 substituents independently selected from R14. 20 Embodiment 56. The compound of Embodiment 55 wherein R1 is a benzene ring optionally substituted with up to 4 substituents independently selected from R14. Embodiment 57. The compound of Embodiment 55 wherein R1 is optionally a bite ring substituted with up to 4 substituents independently selected from R14.

The compound of Embodiment 57, wherein R1 is a 4-acridine ring optionally substituted with up to 4 substituents independently selected from R14. Embodiment 59. The compound of Embodiment 58 wherein R1 is optionally 5-substituted with 1 to 3 4-pyridine rings independently selected from substituents of R14, wherein the substituent is located in the The 2-position of the 4-pyridine ring (ie, the nitrogen atom adjacent to the pyridine ring and interphased to the linkage of the pyridine ring to the remainder of Formula 1). The compound of Embodiment 59, wherein R1 is a 4-pyridine ring which is optionally substituted with a substituent independently selected from R14, wherein the substituent is located in the 4-pyridine ring. 2-bit. The compound of the formula 1 or the compound of any one of the embodiments 1 to 60, wherein each R14 is independently halogen, CH: 4 alkyl, Ci-C4-alkyl, cyano, C2-C4 , C2-C4 halo, C2-C4 fast radical, C3_C4 _blockyl, C3-C6 cyclodextyl, CH:4 alkoxy, QQ haloalkoxy, QQ alkylthio or Ci-c4 halogen Sulfur based. The compound of Embodiment 61, wherein each R14 is independently halogen or Q-C4 haloalkyl. Embodiment 63. The compound of Embodiment 62 wherein each R14 is independently F, Q, Br or CF3. Embodiment 64. The compound of Embodiment 63 wherein each R14 is 25 C1. 33201204254 Embodiment 65. A compound of Formula 1 or any one of Embodiments 1 to 64, wherein R2 is hydrazine, QQ alkyl, QQ alkoxy, C2-C5 alkoxyalkyl, C2-C5 alkane Oxycarbonyl or C2-C5 alkylcarbonyl; 5 Embodiment 66. The compound of Embodiment 65, wherein R2 is hydrazine, fluorenyl, methoxy, C2-C5 alkoxyalkyl or C2-C5 alkoxy . Embodiment 67. The compound of Embodiment 66, wherein R2 is hydrazine, methyl, C2-C5 alkoxyalkyl or C2-C5 alkoxycarbonyl. </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; Embodiment 69. A compound of Formula 1 or any one of Embodiments 1 to 68 wherein each R3 is independently a CrQ alkyl group. Embodiment 70. The compound of Embodiment 69, wherein each R3 is decyl. The compound of the formula 1 or the compound of any one of embodiments 1 to 70, wherein R4 is a hydrazine or a CrQ alkyl group. Embodiment 72. The compound of Embodiment 71, wherein R4 is Η or Q-C2 alkyl. Embodiment 73. The compound of Embodiment 72, wherein R4 is Η20 or methyl. Embodiment 74. The compound of Embodiment 73, wherein R4 is hydrazine. Embodiment 75. A compound of Formula 1 or a compound of any one of Embodiments 1 to 74 wherein R5 is hydrazine. Embodiment 76. A compound of Formula 1 or Examples 1 to 75, wherein R6 is optionally independently selected up to 5 independently.

S 34 201204254 A benzene ring substituted with a substituent of R22 or a pyridine ring optionally substituted with up to 4 substituents independently selected from R22. Embodiment 77. The compound of Embodiment 76, wherein R6 is a phenyl ring or a 5 pyridine ring substituted with 1 to 3 substituents independently selected from R22, wherein one substituent is in the para position (relative to This ring is connected to the bond of the rest of Equation 1.) Embodiment 78. The compound of Embodiment 77, wherein R6 is a phenyl or pyridine ring substituted by 1 to 2 substituents independently selected from R22, wherein one substituent is in the para position. The compound of Embodiment 78, wherein R6 is substituted in the para position with a substituent independently selected from R22 and optionally substituted in the ortho position with a substituent independently selected from R22. A benzene ring or a σ ratio ring. Embodiment 80. The compound of Embodiment 79, wherein R6 is a ring of benzene or substituted at a 15 position with a substituent independently selected from R22. Embodiment 81. A compound of Formula 1 or a compound of Examples 1 to 80, wherein when R6 comprises an acridine ring, the ring is bonded to the remainder of Formula 1 at the 2-position. 2) Embodiment 82. A compound of Formula 1 or a compound of Embodiments 1 to 80, wherein R6 is a benzene ring substituted as described. Embodiment 83. A compound of Formula 1 or a compound of Examples 1 to 81 wherein R6 is a substituted pyridine ring as described. Embodiment 84. The compound of Embodiment 76, wherein R6 is a benzene ring which is optionally substituted with up to 5 substituents independently selected from R22. 35. The compound of Embodiment 84, wherein R6 is a benzene ring substituted with 1 to 3 substituents independently selected from R22, wherein one of the substituents is located in the benzene ring. Bit. Embodiment 86. The compound of Embodiment 85, wherein R6 is a phenyl ring substituted with 51 substituents selected from R22, wherein the substituent is at the 4-position of the phenyl ring.

Embodiment 87. A compound of Formula 1 or a compound of Examples 1 to 86, wherein each R22 is independently halogen, cyano, CrQ alkyl, Ci-C6 halogen, C3_C6 cycloalkyl, C2-C6 Base, 10 C2-C6 haloalkenyl, C2-C6 alkynyl, CrQ alkoxy or CrQ halooxy. Embodiment 88. The compound of Embodiment 87, wherein each R22 is independently F, CBr, cyano, CH3, CF3, cyclopropyl, HOC, CH30 or CF30. The compound of Embodiment 88, wherein each R22 is independently F, a, Br, CF3 or CF30. Embodiment 90. The compound of Embodiment 89 wherein each R22 is independently F, Q, Br or CF3. Embodiment 91. A compound of Embodiment 90 wherein each R22 is independently F, C1 or CF3. Embodiment 92. The compound of Embodiment 91 wherein each R22 is F or a. Embodiment 93. A compound of Formula 1 or any one of Embodiments 1 to 92 wherein the oxime is 0, S or NR36 (i.e., k is 0). 25. A compound of embodiment 93 wherein T is 0 or NR36.

S 36 201204254 Embodiment 95. The compound of Embodiment 94, wherein T is 0. Embodiment 96. A compound of Formula 1 or any one of Embodiments 1 to 95 wherein R36 is hydrazine. Embodiment 97. A compound of Formula 1 or a compound of any one of Embodiments 1 to 96, wherein W is a hydrazine. Embodiment 98 - A compound of Formula 1 or a compound of any of Embodiments 1 to 97, wherein W1 is hydrazine. Embodiment 99. A compound of Formula 1 or any one of Examples 1 to 98, wherein each W2 is in the form of hydrazine. 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。. Embodiment 101. The compound of Embodiment 100, wherein η is 0 or 1. Embodiment 102. The compound of Embodiment 101 wherein η is 0. 15. The compound of formula 1 or any one of embodiments 1 to 102, wherein ρ is 0 or 2. Embodiment 104. The compound of Embodiment 103, wherein ρ is 0. Embodiment 105. A compound of Formula 1 or any one of Examples 1 to 104, wherein s is 1. 2) Embodiment 106. A compound of Formula 1 or any one of Examples 1 to 105, wherein t is 1 . Embodiment 107. A compound of the invention or any one of embodiments 1 to 106 which is not present in the form of an N-oxide. 25 Embodiment 108. A compound of Embodiment 107 which is not in the form of an N-oxide or a salt. 37. The compound of the invention or the compound of any one of embodiments 1 to 108, wherein R7 is not NH2. Embodiment 110. The compound of Embodiment 109, wherein R7 is other than NR24R25. 5 Embodiments of the invention, including the above Examples 1 to 110 and any other embodiments described herein, may be combined in any manner, and the description of the variables in the examples is not only related to the compound of Formula 1, but also to The starting compounds for the preparation of the compounds of formula 1 are related to intermediate compounds. Further, the embodiments of the present invention, including the above Examples 1 to 11 () and any other embodiments described herein, and any combinations thereof, relate to the compositions and methods of the present invention. Combination of Examples 1 to 110 Description: Example A1. The compound of Formula 1, wherein T is 〇; 5 z is 〇; R1 is substituted by 1 to 3 substituents independently selected from R! Wherein one of the above substituents is located at the 2-position (2-2position) of the 4·0-pyridine ring; R2 is Η'methyl, C2_C5 alkoxyalkyl or c2_c4 alkoxy^ a carbonyl group; an R4 system or a C!-C4 alkyl group; an R5 system; R is a benzene ring optionally substituted with up to 5 substituted 5 groups independently selected from R22 or optionally up to 4 independently selected a pyridine ring substituted with a substituent of R22;

S 38 201204254 R, R8, 尺9 and Rl〇 are independently Η, halogen, Cr_C4 alkane f Cl c4 13⁄4 alkyl, c2_c4 dilute, dentate ς C2匚4, c3_c4 _ fast, ^ naphthenic , Cr~C4 alkoxy, c-C4 alkoxy, Cl-^ 8 thio, Cl-c4 haloalkylthio or cyano, or R7 and 4 =, or R8 and V, or R9ARH) The carbon atoms to which the adjacent couple, the ring and the like are joined together form a 5- or 6-membered aromatic or non-aromatic ring comprising a ring member selected from the group consisting of carbon atoms and to (a) and (hetero) atoms; Is independently hydrazine, halogen or methyl; each R13 is halogen or methyl;

Each R14 system, which is i, Ci_c4, Ci_C4, cyano, C2-C4 alkenyl, C2_C4 haloalkenyl, C2_C4 alkynyl, c3-c4 i alkynyl, c3-Cpf alkyl, Ci —Q alkoxy, CVCt consists of alkoxy, Ci—c4 alkylthio or Ci-c4 ialkylthio; 20 each R22 is independently halogen, cyano, Ci_c6 alkyl, Ci—C6 dentate, C3 —C6cyclohexyl, c 2 —c 6 alkenyl, c 2 —c 6 halo, C: 2—C 6 alkynyl, C-C6 alkoxy or CVQ haloalkoxy; R 34 hydrazine or CrC 2 alkyl; R 35 hydrazine ; W system 0; η system 0; s system 1; and t system 39 25 201204254 Example A2_ The compound of Example A1, wherein A1 is N or CR7; A2 is N or CR8; A3 is N or CR9; A4 is CR10; L is -C(Ru)=c(R12)-, -C(R34)(R35)〇- or unsubstituted diphenyl; R1 is one substituent selected from R14 Substituted 4-pyridine ring 'wherein the above substituent is located at the 10 2-position (2-p〇sition) of the 4-pyridine ring; R2 is Η; R4 is Η or methyl; R is 1 to 3 independent a benzene ring or a "pyridinium ring" substituted with a substituent selected from r22, wherein one substituent is in the 15 position; R7, R8, R9 and Ri The 〇 is independent of Η, halogen or c-C4 halogen base; R11 and R11 are independent of each R14! I or c "c4 haloalkyl; 20 each R22 is independently F, C, Br, cyano, CH3, CF3, cyclopropyl, HOC, CH30 or CF30; and R34 is H or fluorenyl. Example 6A3 a compound of embodiment A2 wherein R is substituted in the para position with a substituent independently selected from R22, and optionally substituted in the ortho position with a phenyl ring independently substituted with a substituent selected from R22 or Acridine ring

S 201204254 R7 is Η or p; R and R are independently H, halogen or Ci_C4 dentate; R is Η or ρ; each R22 is independently F, C, Br or CF3; and each 11 is independently F, C Br Br, CF3 or CF30. Embodiment 6 The compound of Embodiment A3 wherein R is a benzene ring substituted in the ortho position with a substituent selected from the group consisting of R22; R7 system; R8 system ruthenium, halogen or cf3; R9 system ruthenium, halogen or cf3 R10 system Η; R14 system Cl; and R22 system F, a, Br or CF3. Particular embodiments include a compound of formula 1 selected from the group consisting of 2-gas·Ν-〇[[1·[(2Ε)-3-(4-chlorophenyl)-2-propene-1 -yl]-3-azetidinyl]oxy]-6-(trifluoromethyl)-3-acridinyl]-4.-bipyridylcarboxamide, and 2·chloro-N-[4,5- Diqi-2-[[1-[(2Ε)-3-(4-carbophenyl)-2-propen-1-yl]-3-azetidinyl]oxy]phenyl]-4-acridine Carboxylamidine, 2-chloro-N-[6-chloro-2-[[1-[(2Ε)-3-(4-carbophenyl)-2-propen-1-yl]-3-azetidinyl] Oxy]-5-fluoro-3-. Bipyridyl]-4-. Bipyridine carboxamide, 201204254 2-chloro-N-[5-chloro-2-[[1-[(2Ε)-3-(4-phenylphenyl)-2-propenyl-l-yl]-3- Azetidinyloxyfluoro-3-pyrylpyridyl]-4·acridine carboxamide, 2-chloro-N-[2-[[1-[(2Ε)-3-(4-phenylphenyl)) -2 propen-1-yl)-2-methyl-3-0 丫 σ 定 ]] oxy]_6-(trifluoromethyl)-3-indole ratio bite base] -4- 〇 〇 叛 叛 叛Amine, and 2-chloro-^-[6-gas-2-[[1-[2-(4-cyclophenoxy)propyl]-3.丫丁基基]oxy]-5-fluoro-3-α than bite base]-4-ni; b bite the amine. Notably, the compounds of the invention are characterized by advantageous metabolism and/or soil residual patterns&apos; and exhibit control of the activity of a variety of agronomic and non-agronomic invertebrate pests. It is particularly noteworthy that the protection of crops from invertebrate pests by controlling invertebrate pests is an embodiment of the invention for reasons of invertebrate pest control and economic value. The compounds of the present invention also protect leaves or other parts of the plant which are not in direct contact with the compound of the formula or the composition comprising the compound, due to its good transfer characteristics or systemic properties in the plant. Further notable embodiments of the invention are compositions comprising any of the prior embodiments and any other embodiments described herein. And an additional component selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent, the composition optionally further comprising at least one additional biologically active compound or agent. Further noteworthy embodiments of the invention are compositions for controlling invertebrate pests comprising any of the prior embodiments and any other of the compounds described herein and any combination thereof, and at least one selected Free-surfactant, a solid diluent and a

S 201204254 An additional component of the group consisting of liquid diluents, which composition optionally further comprises at least - additional biologically active compound or agent. DETAILED DESCRIPTION OF THE INVENTION The present invention includes a method of controlling occipital pests, a mono-compound or a combination thereof (for example, in the form of a composition) of any of the embodiments of the invertebrate lesions in an environmentally and biologically effective amount thereof. )contact. Embodiments of the invention also include a composition in the form of a soil comprising a combination of a singular character of any of the previous embodiments. The embodiment of the present invention further comprises a method for controlling invertebral motion, which comprises making a field (four) earth money. In the case of physical contact, the composition comprises a single compound or a combination thereof in which the silk is effective. Any of the embodiments of the present invention 15 20 embodiments of the present invention also include a spray composition for pests, a single compound comprising a first meeting, a 1-invertebrate, or a combination thereof, and a biologically effective Examples further include - a control composition for use in a control-invertebrate movement, comprising any of the previous embodiments - a bait group of a pest or a combination thereof, or a plurality of food materials, a single amount of a single agent, and A selective use of a humectant. The present invention selectively employs an inducer for controlling an invertebrate worm. U. The embodiment also includes a species and a suitable composition. The hybrid composition has one opening, and the size of the opening is set. Wherein the outer shell has access to the opening, such that the invertebrate vertebrate is placed close to the composition, and wherein; the potential of the invertebrate is outside the outer shell or has been placed at 43 25 201204254 The present invention also includes a method of protecting a seed from invertebrate pests comprising a compound (single-compound or combination thereof) of any of the foregoing embodiments in an amount effective to the seed with a biologically effective amount. Embodiments of the invention also include a method of protecting an animal from insults, which comprises administering to the animal a parasiticidally effective amount of a compound of any of the foregoing examples (single-compound or combination thereof). An embodiment of the present invention also includes a method of controlling an invertebrate pest comprising 'a compound of formula 1 or an N-oxide thereof or a salt thereof effective to render the non-organized animal pest or an environmentally acceptable substance thereof (for example, 10 The form of the composition in the form of a contact is a method in which the method is not medically treating a human or animal body by therapy. The present invention also relates to the method in which the invertebrate pest or its environment is made Contacting the composition, the composition comprising a biologically effective amount of a compound of formula 1, an N-oxide or a salt thereof, and at least one group selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent The other group of the group, the composition optionally further comprising a biologically effective amount of at least one other biologically active compound or agent, with the limitation that the methods are not A method of medically treating a human or animal body by therapy. 20 Embodiments of the invention also include any of the foregoing embodiments (single or a combination thereof) wherein the invertebrate pest is an arthropod. Embodiments of the invention are also Included in any of the preceding embodiments, wherein the arthropod is selected from the group consisting of an insect, a worm, a spider, a scorpion, an entertainment, a horse, a stag beetle (p(1) bugs), and a phylum (Symphylans). Embodiments also include any of the foregoing embodiments, wherein the arthropod is an insect.

S 44 201204254 Embodiments of the invention also include any of the preceding embodiments (single or a combination thereof), wherein the invertebrate pest is a gastropod. Embodiments of the invention also include any of the foregoing embodiments, wherein the gastropod is selected from the group consisting of snails, scorpions, and other stalks. One or more of the following methods and variations as described in Schemes 1 through 27 can be used to prepare compounds of Formula 1. Unless otherwise stated, 8.1, A2, A3, A4, L, T, R1, R2, R3, r4, R5, r6, R36, w, k, η, 10 15 20 s and t are compounds of the following formulas 1 to 34 The definitions are as defined in the above summary. Equations la to Id, 1U, 1% to 17d, 2〇a, 22a, 24a, 26a to 26c, 30a, and 31&amp; are respectively of the formulas i, u, 17, 2, 22, 24, 26, 30, and 31 Various subsets. Unless otherwise stated, any substituent of the formula u to Id is as defined above for the formula. As shown in Scheme 1, in the method - the compound of the formula 1 &amp; (meaning that the formula h wherein R5 is H) is by the acid or ketone of the formula 2 and the formula 3 and a suitable κ State 丨 ru Tiantong original agent (for example: NaHB (OAc) 3 or leg 3 feet) in - appropriate solvent (for example: tetrahydrogen ((deleted or f two nipples reacted. • the reaction - (d) in the vicinity of the ring The boiling point can contribute to the reaction. The step of heating to the solvent of Example 4, step D, the synthesis example from the synthesis of the reaction E and the synthesis of the example 8 step 0: Synthesis of the step 7 of the scheme 1 45 201204254

R6〆

L 3

R4 reducing agent

Solution cutting

Equation 2丫: In another method, the compound of formula 1 is a burn-in agent by means of a detached ( ( (wherein &amp; -- cleavage group: 脱,?, for example, * hydride (for example: Br, or monosulfonate ( Example 1 % acid salt, difluoro sulfonium acid salt)) is prepared by reacting in a suitable assay in the presence of a suitable colostant such as triethylamine, anthraquinone, monoisopropylethylamine or carbonic acid. The solvent is, for example, acetonitrile, hydrazine, ν·dimercaptoamine (DMF) or THF. The reaction is generally carried out at a temperature close to 10 ° C, but cooled to -20 ° C or heated to below 120 °. The boiling point of C or solvent may be advantageous for the reaction. The method of Scheme 2 is illustrated by the step D of Synthesis Example 5. Scheme 2

S 46 201204254 10 15 As shown in Scheme 3, in another method, the compound of formula la is obtained by the oxime of formula 2 and the aldehyde of formula 5 (or trimeric road of R4 system) and boric acid (formula 6). , γ 〇Η) or a derivative thereof such as a boronic ester (for example, Formula 6, wherein fluoroborate (Formula 7, wherein Μ φ is a relative ion) is prepared by reacting in a suitable solvent, optionally having - Lewis An acid catalyst (for example: BF; 3 · hydrazine 2 or butyl $4) is present, the solvent is, for example, toluene, L2-diethane, hydrazine, 'dioxin^ or ethanol. The reaction is generally at ambient temperature and the solvent The boiling point is between 'and the reaction mixture can be heated by microwave radiation. Examples of such conditions can be found in several references, such as Tetrahedr〇n Uu 2004, 3471-3474; Tetrahedron Lett. 2005, 8027-8031; Chemtracts 2001, 14(14), 796-801 and the references cited therein. The method of Scheme 3 is illustrated by the step ρ of Synthesis Example 1. Scheme 3

R6'V 6 2 + R4CHO + or --- ia In the method of Scheme 4, the compound of formula 1 (wherein R 2 is not η) 2 is a compound of formula 1 b (that is, formula 1 wherein r 2 is η ) and a suitable base (for example: sodium hydride or lithium hexamethyldiamine lithium (UH) VIE) S)) and a compound of formula 9 (wherein X 2 is a cleavage group such as a halide (Example 47 201204254 eg Cl, Br) Or a continuous acid salt (for example: fluorite, trifluorosulfonate)) is prepared by reaction in a suitable solvent (for example: THF or DMF). The reaction is generally carried out at near ambient temperature, but cooling to -20 ° C or heating to below 120 ° C or the boiling point of the solvent may be beneficial.

S 48 201204254 Scheme 4

In the method of the second scheme, the intermediate of the formula 2 is derived from a suitably protected derivative of the formula 10 (wherein the pg is a protecting group, for example, a tertiary butoxy group, a diphenylmethyl group or (particularly) When dibutyl NH) difluoroacetamido) is prepared by the protection of the conditions well known to those skilled in the art, in Tw Green and PG Wuts, Protecting Groups in Organic Synthesis

Review by Wiley, 1991, pages 327-329 and 364-365. The method of Scheme 5 (wherein Pg is B〇C) is by the step e of the synthesis example i, the step D of the synthesis example 4, the step c of the synthesis example 5, the step C of the synthesis example 6, the step D of the synthesis example 7, and The step c of Example 8 is synthesized. 49 201204254 Scheme 5

5 As illustrated in Scheme 6, the compound of formula 10 is an amine compound of formula 11 (wherein Pg is as defined in Scheme 5) and an acid or derivative of formula 12 (wherein, for example, X3 is OH or C1) It is prepared in the art by reaction under the conditions conventional to those skilled in the art, and these conditions are described in several textbooks, for example: J. March, Advanced ίο Organic Chemistry, Wiley, 1992, pages 417-421. Illustrative conditions include treatment of an amine compound of formula 11 in the presence of RtOCl (e.g., formula 12) in the presence of a suitable base (e.g., triethylamine) in a suitable solvent (e.g., THF or CH2C12), or by RtC ^H (as in Formula 12) and an activator (for example: (benzotriazol-1-yloxy)tris(diamineamine 15yl)hexafluorophosphorus scale (CAS # 56602-33-6, B0P reagent) The amine compound of formula 11 is treated in the presence of a suitable assay (e.g., 4-methyl® &gt;#) in a suitable solvent (e.g., DMF). The reaction is generally carried out between 0 ° C and ambient temperature, although cooling to -20 ° C or heating to below 80 ° C or the boiling point of the solvent may be beneficial. The method of Scheme 6 2〇 method (where X3 is C1) is synthesized by the step D of Synthesis Example 1.

S 50 201204254: Step B of Example 4, Step B of Synthesis Example 5, Step B of Synthesis Example 6, and Step B of Synthesis Example 8 are illustrated. Option 6

A compound of formula 10 wherein Pg is an oxidatively stable protecting group (e.g., BOC) 'T system s(0)k' and k is 1 or 2) can be from a corresponding compound of formula 10 (where k is a low integer) By using a suitable oxidizing agent 10 15 (for example: 2_chloroperoxybenzoic acid (MCPBA) or potassium peroxymonosulfate complex salt (OXONE®)) in a suitable solvent (for example: methylene chloride or water respectively) Prepared by oxidation in an alcohol mixture). The degree of possible oxidation is determined by the relative amount of oxidant. A test such as sodium bicarbonate can be included in the reaction mixture. The oxidation is generally prepared at ambient temperature 'although, such as _2 (TC low temperature or as high as 8 〇. (10) high temperature can be favorable for the reaction. In the method of Scheme 7, R2 is not a compound of formula n (wherein Pg is as in Scheme 5) (Defined as defined herein) by preparing a compound of formula Ua (ie, $11' wherein R2 is H) and a compound of formula 13 (wherein χ4 is an ex situ), generally prepared by reaction in a suitable solvent. Compounds of formula 13 based on formula 4 and reaction strips 20 suitable for attachment to R2 are known in the art of derivatizing amine groups. The general deionization groups include halides (e.g., Cl, Br, I) and the hydrochlorides. (e.g., a citrate salt, a triflate). When R2 is a monoalkyl group, the iodine group is particularly useful. A variety of tests can be utilized, and the choice of the mode of view 13 and whether the test is used for the formula 11 a amine deprotonated or only as an adsorbent from the acid by-product of the reaction. Strong bases (eg sodium hydride) can be used for deprotonation, while tertiary amine bases (eg triethylamine) are available As an acid adsorbent in the reaction, wherein R2 is a mercapto group. Useful solvent Including polar aprotic solvents such as THF and DMF. Methylene chloride is particularly useful when R2 is a mercapto group and the base is a tertiary amine. The reaction is generally carried out at ambient temperature 'although cooling to -20 ° C or heating To the point below 120 ° C or the solvent of the Buddha can be favorable for the reaction.

Scheme 8 illustrates the preparation of a compound of the formula Ua (wherein the Pg is as defined in Scheme 5), which is prepared by reduction of the corresponding nitro compound of formula 14; when the substituents r7, r8, r9 and rig Consistent by hydrogenation of the catalyst or by dissolution of the metal. Examples of catalyst reduction involve hydrogen sources (eg, molecular hydrogen (preferably at atmospheric pressure to 35 〇 kpa)

S 52 201204254 pressure range, although higher pressures can be used or 1,4-cyclohexadiene or ammonium formate), and metal catalysts (eg palladium (preferably supported by carbon or other substrates such as carbonic acid) Calcium) or platinum (optionally supported by carbon or oxidized)) is utilized in its elemental form or in its oxide form. The reaction is typically carried out in ethanol, methanol or ethyl acetate at ambient temperature, although the temperature can be raised up to the point of the solution. Careful selection of conditions (meaning low pressure, short reaction time) is necessary for the case of Pg-based or diphenylmethyl groups. Examples of the dissolved metal reduction include the use of fine iron powder (e.g., a particle size of 10 μηη) in acetic acid or in aqueous ethanol containing a catalyst (e.g., ammonium sulfide). The anti-corridor is carried out at an elevated temperature, preferably in the range of from 7 (rc to 、, 容佛点. When other reducible functional substances (e.g., olefinic halides) are present in the compound When the conditions are ς = the dissolved metal reduction method of the scheme 8 is a step of synthesizing the example Niu C, the step of synthesizing the example 4, and the step of synthesizing the example 6

The amine compound of lla lla (whose T is not NH) is formed by a library or, in the method of Scheme 9, wherein the Pg system is as defined in Scheme 5, and the 53 20 201204254 Ertis rearrangement reaction is formed in situ. Prepared by a mercapto azide compound, for example, by treating a carboxylic acid of formula 15 with azide diphenyl phosphate or by converting an acid of formula 15 to an acid vapor (eg: #processed with grass brewing gas) It is then prepared by reaction with an azide source such as sodium azide in the presence of a test such as triethylamine. In a solvent such as toluene, the rearrangement reaction is preferably carried out in an elevated temperature from the order to the boiling point of the solution. The mixture is then hydrolyzed to release the amine compound of formula 11a. Alternatively, the rearrangement reaction can be carried out in an alcohol solvent (e.g., using tertiary butanol as a solvent) which provides the aniline in a protected form of BOC. The amine compound of formula 11a is then released by treatment with a strong acid such as trifluoroacetic acid or hydrogen sulfide in an ether solvent. Modifications to this Scheme 9 method, and Pg is generally selected from an acid-resistant group such as a benzyl group to avoid loss during treatment with a strong acid. The Kurtis rearrangement reaction is outlined in J. March, Advanced Organic Chemistry, Wiley, 1992 pages 1091-1092; see also 〇rg. synth., Coll. Vol. 6: 910-913. Option 9

· · (PhO) 2 (〇) N3 or (C0C1) 2, followed by 4 gas compound source / base 2. Hydrolysis or deprotection

Lla 20 15 201204254 In the method of Scheme 10, wherein the T system is 0, S or NR36, a compound of formula 14 is protected by the compound of formula 16 wherein X5 is a suitable cleavage group such as a halide The proterenol (wherein Pg is as defined in Scheme 5) in the presence of a suitable base (eg sodium hydride, 5 sodium hydroxide or potassium carbonate) and in a suitable solvent (eg DMF, acetonitrile, THF or toluene) Prepared by reaction. When A1 is CR7, X5 is preferably F, and when A1 is N, X5 of C1 is also generally effective. The reaction is generally carried out at ambient temperature, although cooling to -20 ° C or heating to below 80 ° C or the boiling point of the solvent may be beneficial. The method of Scheme ί 10 is illustrated by the synthesis of Step B of Example 1, Step A of Synthesis Example 6, and Step B of Synthesis Example 7. Option 10 Pg

16 17 14 15 a compound of formula 14 (wherein Pg is a oxidatively stable protecting group (eg BOC), T system 3 (0^ and k is 1 or 2) can be derived from the corresponding compound of formula 14 (where k is a low Integer) is prepared by oxidation with a suitable oxidizing agent. Suitable oxidation conditions are prepared as described in Scheme 2〇6 for the corresponding compound of formula 10 (where k is a 55 201204254 low integer) The compound of formula 10 (wherein the T system S(0)kX k is 1 or 2) has the same conditions. In the method of Scheme 11 (wherein T is 〇, s or NR36), the vinegar of formula 19 (wherein the Ra-based low-carbon alkyl group) , for example, methyl, ethyl, tert-butyl) by the compound of formula 18 (wherein X5 is suitably decoupled from a group such as a halide) and the protected alpha oxime of formula 17. (wherein Pg is as defined 5) is prepared by examining the presence of a solvent and reacting under the reaction conditions as described for the method of Scheme 10. When A1 is CR7, X5 is preferably F, and when A1 is N, 'X5 is The ci is also generally effective. Then, the ester of the formula 19 is saponified by using an aqueous test (for example, Na〇H), and then, if it is an oxime ester and a Then, by acidification, or as a tertiary butyl ester, it is converted into a carboxylic acid of the formula 15 by treatment with a strong acid (for example, trifluoroacetic acid or a solution of hydrogen chloride in ethanol or dioxane). A cosolvent such as two gases may be added. Methane to increase solubility. In aqueous saponification mixtures, ethanol and dioxins are used as cosolvents to increase the solubility of esters of formula 19. The conversion of esters of formula 19 to formula 15 is generally carried out at ambient temperature, however cooling Up to -20 ° C or heating to below (7) ❶芄 or the boiling point of the solvent may be beneficial to the reaction. Many other conditions may also affect this conversion, and a variety of protecting groups other than Ra low carbon carboxylic acid can be used in Scheme 11 In the method, the relevant references can be found in τ w Greeneand PG Wuts, Protecting Groups in Organic Synthesis, Wiley, 1991, pages 229-263. s 56 201204254 Scheme 11 Pg

15 Ra-based lower alkyl (for example: methyl, ethyl, tert-butyl) compound of formula 15 (wherein Pg is an oxidatively stable protecting group (eg B〇C) 'T-system S(0)i^ The k-system i or 2 can be prepared from the corresponding compound of the formula (wherein k is a lower-order integer) by oxidation with a suitable oxidizing agent. The oxidation conditions suitable for the t are as described in the scheme 6 The corresponding compound of the formula 1 (wherein k is a lower integer) is prepared under the same conditions as the compound of the formula 10 (wherein the T system is s(0)k and the k is 1 or 2). b In the methods of the schemes 10 and 11, one Nitro or alkyl in the ortho position

The substitution of the (X〇2Ra) substituent activates the cleavage group X5. When A1 is N, as described in Step A of Synthesis Example 8, the presence of an activating substituent may not be required. As described in Scheme 12, wherein the T system is 〇, s or NR36, the compound of formula 22 (wherein the combination of E and G is related to formulas 1, 1, 、, 14, 19 and 25) is also obtained by reacting a hydroxyaromatic compound of formula 20 with Formulations of the formula 21 having a suitable cleavage group (X6) such as a methyl ester or a bromide are prepared by reaction in the presence of a suitable assay (e.g., ICCb, NaH or LiHMDS). 201204254 The reaction is generally carried out at ambient temperature, although cooling to -20 ° C or heating to below 120 ° C or the boiling point of the solvent may be beneficial. Option 12

E system N02, C〇2Ra or NI^CWR1 'R&quot; is a carboxylic acid protecting group, for example, a lower alkyl group G is a protecting group Pg or CRf-L-Re 10 15 as defined in Scheme 6. It is prepared by a variety of methods known in the art of organic chemical synthesis. It is worth noting that the compound of formula 20 (where T is S) is prepared from the corresponding compound of formula 20 (where T is 0) by Newman-Kwart rearrangement (see Dirk Kusch,

Specialty Chemicals Magazine 2003, 23(9), 41). As shown in Scheme 13, the compound of formula 22a (ie, formula 22, wherein T is Ο) is also from the intermediate of formula 20a (ie, formula 20, wherein T is Ο) and formula 23 (ie, formula 17 or 26, wherein the T is 〇) Prepared under the Mitsunobu conditions as described, for example, in Bioorg. Med. Chem. Lett. 2008, 18, 5581-5585. TMF is a particularly useful solvent, and the reaction is generally carried out between -20 ° C and ambient temperature, although heating to 60 ° C may be beneficial. The method of Scheme 13 is illustrated by the step A of Synthesis Example 4. s 58 201204254 Scheme 13

G

20a 23 G Rb0C(O)N=NC(O)ORb PPh3 -- Solvent

22a E is N〇2, Cc^Ra or NR2C(W)Ri, a furnace carboxylic acid protecting group such as a lower alkyl group. G is a protecting group as defined in Scheme 6, 8 or 〇^. Preferably, 驴 or i-Pr · as illustrated in Scheme 14, a compound of formula 1 or by an acid derivative of the formula 12 wherein X3 is, for example, 〇H or α, is similar to that of Scheme 6 above. Prepared by formula 24 aniline. The disclosure document providing the method of Scheme 6 provides the method of Scheme 14. The method of Scheme 14 is illustrated by the step D of Synthesis Example 2. 10 Scheme 14

In the method of Scheme 15, the compound of formula 24 (wherein R 2 is not η) is prepared by reacting a compound of formula 24a (ie, formula 24, wherein R 2 is a hydrazone) with a compound of formula 13 wherein X 4 is a suitably delocalized group. , 59 15 201204254 Generally using a base in a suitable solvent, similar to the method of Scheme 7 above. The disclosure document providing the method of Scheme 7 provides the method of Scheme 15. Option 15

In the method of item 16, the amine compound of the formula (10) is prepared by the glutamic acid compound of the ruthenium, which is similar to the above scheme. * The disclosure of the method of the method of claim 8 provides the L system 16 of the method of claim 16, wherein the dissolution of the dissolved metal is preferably a hydrogenation when it is applied to the right. Reducing with dissolved metals. ', 16 methods are described by the step D of the synthesis example 2

S 201204254 In the method of Scheme 17, wherein the τ system is 〇, s or ^^36, the 25 nitro compound is obtained by the compound of the formula 16 (wherein the χ5 system is suitable for the cleavage group, for example, the * compound) The α-oxime is prepared by reacting in the presence of a suitable two-agent, similar to the method of the above scheme. = The disclosure document for the method of Scheme 10 includes the method of Scheme 17. However, the method of the method is as high as 12G. (3) The temperature or the boiling point of the solvent may be advantageous for carrying out the reaction. The method of Scheme 17 is illustrated by the step B of Synthesis Example 2. α Scheme 17

The aromatic compounds of the formulae 16, 18 and 20 can be prepared by a variety of methods known in the art of organic chemical synthesis. Compounds of formula 26 can also be prepared by a variety of methods. The method of the following Scheme 18 is particularly useful for the preparation of the compound of the formula 26 wherein γ is 〇, and s and t are each 1. As shown in Scheme 18, 'Formula 26a oxime (i.e., Formula 26, wherein Y is Ο, and s and t: each 1) can be obtained by substituting an amine of formula 28 with an alcohol of formula 27 (wherein X6, And most typically alpha) or a derivative thereof, optionally in the presence of an additive (e.g., triethylamine or bromine 61 201204254 magnesium), according to the disclosed procedures (e.g., J. Het. Chem. 1971, 8, 1059- 1062; J. Org. Chem. 1967, 32, 2972-2976; Tetrahedron Lett. 1997, 6059-6062). The method of Scheme 18 is illustrated by the synthesis of Example 2, Step A. The amine of Formula 28 can be prepared by methods well known in the art; for example, cinnamamine can be as described in J_ Org. Chem. 1982, 47, 5395-5397. The general method of preparation. Option 18

Processes for the preparation of protected 17-denier, pyrrolidine and piperidine (wherein lanthanum or NR36) substituted with hydroxy and amine groups are customary in the field of organic chemical synthesis and a plurality of such compounds are Commercially available. Scheme 19 illustrates a method similar to that of Scheme 18 for the preparation of a hydroxy substituted protected formula 17a (i.e., Formula 17, wherein τ is 0) oxime. Once (i.e., protected 吖), wherein Pg is, for example, a diphenylmethyl or benzyl group. In this process, a protected formula 17a sterol is prepared by reacting a protected amine of formula 29 with an epihalohydrin of formula 27 using such procedures as described in Scheme 18. Furthermore, use the general methods known in the field (eg ' T. W. Green and p g do not do

Protecting Groups in Organic Synthesis, Wiley, 1991, pp. 327-329 and 364-365) The protective group can be derived from the formula na

S 201204254 (wherein Pg is, for example, a diphenylmethyl or benzyl group) is removed and then attached. Another protecting group is attached to form a protected form 17a. Sterol (where pg is for example BOC). The compound of the formula 17a wherein Pg is B〇c and n is 〇 is commercially available. Option 19

3, as shown in Scheme 20, formula 26b oxime (ie, formula 26, wherein 1 〇 R3 is not attached to the 3-position of the oxime ring) (where η is an integer from 0 to 4) The ketone of the formula 30 is prepared by reduction with a reducing agent (for example, sodium borohydride in decyl alcohol or ethanol) using a procedure similar to that described in U.S. Patent No. 36,681%. Option 20

15 = hour 'as shown in Scheme 21, protected formula 17b sterol f17 / medium T system 〇 ' and R3 is not attached to the ° 丫 ° ring 3 position), η system from 0 to 4 An integer of the formula, and the protecting group defined by 63 20 201204254 in Pg-Scheme 5 can be prepared by reducing the hydrazine of the formula 31 with a reducing agent, similar to the method of Scheme 20. Option 21

In the method of Scheme 22, the formula 26c is a thiol alcohol (i.e., Formula 26, wherein R3 (e.g., R3a) is attached to the 3-position of the anthracene ring) (where η' is an integer from 0 to 4, and R3a The alkyl group is prepared by adding an organic reagent of the formula 32 (for example, an organic or genomic reagent) to the formula 30 oxime in a test solvent (for example, diethyl ether or THF). The above is at ambient temperature or preferably cooled to a low temperature such as -78 ° C, and utilizes the well-known procedures in the art (for example: Tetrahedron Lett. 1972, 5063-5064; U.S. Patent No. 3,668,196). 15 Scheme 22

M2 is, for example, Li, MgCl, or MgBr. Similarly, as shown in Scheme 23, the protected formula 17c is a 2-mer alcohol (i.e., Formula 17, wherein T is 0, and R3 (e.g., R3a) is attached to 吖

S 64 201204254 5% of the mouth) (where n is an integer from 〇 to 4, Rh is an alkyl group, and Pg is a protecting group as defined in Scheme 5) by using an organometallic compound of formula 32 Prepared by addition to the protected formula 31 in the ether solvent, analogous to the method of Scheme 22. Option 23

1^ is an alkyl group; OH J7c Μ2 is, for example, Li, MgCl, MgBr. Formulas 30 and 31 can be prepared by conventional methods well known in the art. For example, as shown in Scheme 24, a pair of disubstituted formula 3〇a oxime ketones (i.e., Formula 30 in which the 2 _ position of the oxime ring is substituted with two R 3 ) can be used as a base (eg, : Sodium bicarbonate) is prepared by treating a corresponding oxime-bromo-2-butanone of the formula 33 in a solvent (for example, DMF or aqueous methanol), which is similar to that described in U.S. Patent No. 3,668,196. Process. Option 24

Solvent

The care and tether are independently alkyl. 65 201204254 5 Similarly, as shown in Scheme 25, a protected pair of disubstituted formula 31a oxime ketones (ie, formula 31 wherein the 2-position of the oxime ring is replaced by two R3) (where Pg Preparing a suitable protecting group, for example, a diphenyl fluorenyl or benzyl group, can be prepared by treating a corresponding 1-bromo-2-butanone of formula 34 using a reaction condition similar to that described in the method of Scheme 24. 0 Scheme 25

Ruler 31&gt; and the oxime are independently alkyl groups. 10 As shown in Scheme 26, the formula nd thiol compound (i.e., formula 17, '糸S) can be treated by the thiol nucleophile Na s S relative to the presence of ruthenium (e.g., NaH). Heart / in! (iv) - Appropriate protecting groups, such as gSH (the thiol nucleophile, - soil (Bn)) form appropriate

For this, deprotection with sodium in thiol hydrazines such as liquid ammonia. DMF heating (for example = the relevant displacement reaction is a good solvent and mildening of King 80 C) facilitates the reaction.

S 66 201204254 Scheme 26

twenty one

Na2S/DMF or

1. BnSH, NaH/DMF 2. Na/Liquid NH; i 5 The compound of formula 21 can be prepared by a variety of methods known in the art of organic chemical synthesis, including the preparation of a corresponding compound of formula 17 wherein T is 0. A compound of the formula 21 having a s and t of each value in the present document (wherein Pg is BOC, η is 0, and X6 is I or OMs) is commercially available. Certain other compounds of formula 21 wherein Pg is a further protecting group, such as trifluoroethyl, carboxybenzyl (CBz) or diphenylmethyl, are also commercially available. As shown in Scheme 27, a compound of formula lc (i.e., Formula 1, wherein W is S) can be prepared by vulcanizing a corresponding compound of formula Id (i.e., Formula 1, wherein W is 0). Vulcanization involves treatment with a vulcanizing agent, for example: 15 phosphorus pentasulfide or 2,4-bis(4-indolylphenyl)-1,3,2,4-dithiophos, 2,4-disulfide (lawson Lawesson's Reagent), or 2,4-bis(4-phenoxyphenyl)-1,3,2,4-dithiophosphorus, 2,4-disulfide (Belleau's Reagent) )). The reaction is preferably carried out in a solvent such as toluene, dinonylbenzene or dioxane, and at an elevated temperature from 80 ° C to the boiling point of the solvent of 20. 67 201204254 Scheme 27

5 It should be recognized that some of the reagents and reaction conditions described above for the preparation of the compound of Formula 1 may not be compatible with certain functionalities present in the intermediate. In these examples, incorporation of a protection/deprotection sequence or mutual conversion of functional groups into the synthesis will help to obtain the desired product. The use and selection of protecting groups is readily apparent to those skilled in the art of chemical synthesis (for example, see T. W. Greene, P. G. M. Wuts;

Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). Those of ordinary skill in the art will recognize that, in some cases, after introduction of the reagents described in the individual schemes, additional routine synthetic steps not detailed may be required to complete the synthesis of Compound 15 of Formula 1. It will also be recognized by those of ordinary skill in the art that the steps described in the above schemes need to be performed in a combination other than that presented herein to produce a compound of formula 1. Those skilled in the art will also recognize that the compounds and intermediates of Formula 1 described herein can accept various electrophilic reactions, nucleophilic reactions (1), free radical reactions, organometallic reactions, oxidation reactions, and reduction reactions.

S 68 201204254 , + Force substituent or modification of the substituent present. For example, the step "A of the synthesis example 5" illustrates the chemistry of the intermediate. Without further elaboration, it is believed that those of ordinary skill in the art using the foregoing description will still be able to utilize the invention. The following synthesis examples are to be construed as illustrative only and not as a limitation of the disclosure herein. In the following synthesis examples, the Y step 'describes the process of each step in the entire synthesis change, and the starting materials per 2 steps are not determined to be in other examples or steps. Prepared by the process of the special preparation scheme described in 4. The percentages are by weight in addition to the chromatographic solvent mixture or otherwise indicated. Unless otherwise specified, the layer f is a volume fraction and a volume percent. Unless otherwise stated, 'H NMR spectrum is described as ppm, and the tetragonite of CDC13 is "Shi Xiyuan to low magnetic field displacement; "s" represents a single peak, "d" represents a double peak, dd" represents a doublet, and "dt" represents a double peak. Double three ♦, "m" stands for more, "br table width single peak" "brd" stands for wide double peak, and "b pair of d" pairs of double peaks, where the chemical shift difference is not greater than the coupling constant. Mass = MS) Describes the molecular weight of the positive electrophilic ion (M+1) by increasing the H+ (molecular weight n to the molecule) and the abundance of the positive electrophilic ion (M+1). 2 〇S. ^ Loss Η (Knife look: 1) The highest isotope abundance of the applied ion (M-ι) is formed by mass spectrometry using an electrospray ionization (ESI) method, where "Nove" represents the atomic mass unit. Synthesis Example 1 - Soil »pyridyl H-pyridine carboxamide (Compound 1)

69 25 201204254 Step A: Preparation of 2-gas-3-nitro-6_(trifluoromethyl) base bite, mixed in concentrated sulfuric acid (?5mL) and aqueous hydrogen peroxide solution (40%, 37mL)^ A solution of 2·glyconsin (tris-f-)-3-amino-based B in a sulfuric acid (93 mL) was added dropwise at 〇 °C to a bite (7 〇〇g, 35 6 〇 1) solution. 10 15 20 Then put the money in the money temperature for 2Q hours. Batch analysis (20: EtOAc / petroleum ether) showed the reaction was completed. The mixture was poured into ice water and neutralized to pH 8 to 9 by addition of aqueous ammonia, followed by extraction with ethyl acetate (3 χ). The combined organic layer f was dried (Na2EtOAc) elute HNMR 5 8_4 (d, lH), 7.8 (d, lH). Step B · Preparation of 3_[[3-nitro-6-(trifluoromethyl) 2 吼 基 methoxy] oxy] small σ 丫 0 tarar acid 1,1 dimethyl ethyl ester Ν, Ν a solution of 3-hydroxy-1-indole acid 1,1-dimethylethyl ester (2.61 g, 15.1 mmol) in dimercaptocaramine (35 mL) with potassium carbonate (4 g) , 28_9 mm〇1) and 2_gas_3-nitro-6-(trifluoromethyl)pyridine (ie product of step A, K 3 27 g, 14 4 mm 〇 1). The mixture was then stirred at ambient temperature for 5 hours. The reaction mixture was taken care of, and the filtrate was poured into ice water and extracted with ethyl acetate. The organic layer was washed with brine and dried (Na.sub.2). The solvent was evaporated and the residue was purified by column chromatography (EtOAc EtOAc EtOAc EtOAc EtOAc Title product (id g). 4 NMR δ 8.43 (d,1H), 7.5 (d,1H),5·5 (m,1H),4.4 (m, 2H), 4.1 (m, 2H), 1.5 (s, 9H) 〇MS $SI ) 364 amu (M+1). 25 201204254 Step C. 3-[[3-Amino-6-(trifluoromethyl)-2-0 butyl]oxy]-1· 1,1-didecylethyl carboxylic acid Preparation of 3-[[3-nitro-6-(trifluoromethyl)-2-pyridyl]oxy]-1-indolecarboxylic acid in a mixture of ethanol (20 mL) and water (2 mL) Ip,ι_dimercaptoethyl vinegar (ie the product of Step B) (1.5 g, 4.1 mmol) solution, to which iron powder (300 mesh (about 50 μηι), 692 mg, 12.3 mmol) and chlorinated Ammonium (lio mg, 2.1 mmol) and the mixture was heated under reflux for 4 hours. The reaction mixture was cooled, filtered through celite® celite filter and concentrated. The residue was diluted with di-methane and washed with water. The organic phase was dried (Na.sub.2SO.sub.4) and concentrated to afford a white solid (1.2 g). (: melted title product. ^NMR δ 7.18 (d3 1 Η), 6.9 (d, 1 Η), 5.4 (m, 1H)5 4.38 (m, 2 H), 4.1 (br s, 2 H), 3.97 ( m, 2H), 1.45 (s, 9H) MS (ESI) 334 amu (M+l). Step D: 3-[[3-[[(2-chloro-4-)-pyridyl)carbonyl]amine Preparation of yl,-6-(trifluoromethyl)-2-pyridyl]oxy]-i-indolecarboxylic acid ι,ι·dimethylethyl ester in dichloromethane (15 mL) - a solution of 4-pyridylcarbonyl chloride (640 mg ' 3.63 mmol) in hydrazine. (:3-[3-amino-6-(trifluoromethyl)-2-° ratio bite base added thereto] Oxyl] succinic acid 1,1-dimethylethyl vinegar (ie the product of step C) (1.1 g, 3.3 mmol) and triethylamine (1.1 mL, 8.25 mmol) and The reaction mixture was stirred at ambient temperature for 3 hr. then the mixture was diluted with methylene chloride, washed with water and dried (Na2SO4). (95 〇· · mg), the title product melted at 85-87 ° C. · NMR δ 8.85 (d, 1H), 8.65 (d, 1H), 8.38 (s5 1H), 7.79 (s, · 1H), 7.62 (d, 1H), 7.41 (d, 1 H), 5.5 (m, 1H), 4.43 (m, 2H), 5 1.43 (s, 9H). ' MS (ESI) 471 amu (Ml) Step E: N-[2-(3- °丫Preparation of α-danooxy)_6_(trifluoromethyl)_3·0-pyridyl]-2-chloro-4-pyridinecarboxamide A 3-[3-[[in the sterol (145 mL)) [(2·Ga-4-pyridyl)carbonyl]amino]-6-(trifluoromethyl)-2-° ratio methoxy]_i&lt;D-denidic acid dimethyl dimethyl ester (i.e., the product of Step D) (50 〇 mg, 35.0 mmol) of solution 'Ethyl chloride (5 mL) was added dropwise at 0 ° C. The reaction mixture was stirred at 0 C for more than 2 hours and heated to ambient temperature. And the recipient was additionally given a drop of 4 hours. The reaction mixture was concentrated under reduced pressure, dissolved in dichlorohydrazine and washed with 10% aqueous sodium hydrogencarbonate solution and dried (Na2S〇4). The title compound was obtained as a yellow solid ( 275 mg). NMR (DMSO-d6) δ 8.63 (d5 1H), 8.42 (d, 1H)S 7.98 (s, 20 1H), 7.83 (d, 1H), 7.59 (d, 1H), 5.4 (m, 1H), 3.78 (m, 2H), 3.6 (m5 2H), (NH resonance is combined with a broad water peak at 3.36). MS (ESI) 373 amu (M+l). Step F: 2-Chloro-N_[2-[[H(2E)-3-(4-carbophenyl)-2-propen-1-yl]]]-]]- Preparation of fluoromethyl)_3-pyridyl]_4_pyridinecarboxamide

S 72 201204254 Ν-[2·(3-吖ηdyloxy)_6·(trifluoromethyl)-3-pyridyl]-2-a-4-pyridiniumcarboxylate in dioxane (5 mL) a solution of the amine (ie the product of the step oxime) (200 mg, 0.53 mmol), to which was added tris-decanoic acid (25 mg, 0·8 mmol), and the mixture was stirred at 90 ° C for 5 hours while stirring. . Then Β-[(1Ε)-2-(4-chlorophenyl)vinyl (tetra) acid (196 mg, 1.07 mmol) was added, and the reaction mixture was stirred at 90 ° C for 4 hr. The mixture was cooled, diluted with ethyl acetate and washed with aqueous sodium sulfate (1 N). The organic phase was dried (Na.sub.2SO.sub.4). The title compound (compound of the invention) which was melted at 1 〇〇 2 °C. 'H NMR δ 8.87 (d, 1H), 8.61 (d, 1H), 8.48 (s, 1H), 7.83 (s, 1H), 7.7 (d, 1H), 7.4 (d, 1H), 7.3 (s, 4H), 6.5 (d, 1H), 15 6.2-6.12 (m, 1H), 5.42 (m, 1H), 3.84 (m, 2H), 3.4-3.32 (m, 4H). MS (ESI) 523 amu (M+l). Synthesis Example 2 20 2_gas-N_[4,5·dichlorophenyl)-2-propen-1-yl]-3-oxindole]oxy]phenyl] is more than a chiral amine (compound 2) Preparation Step A: Preparation of PW(2E)-3 -(4·Phenylphenyl)_2·Propylene_丨_yl]_3_Loutanol Ethyl Chlorohydrin in 2-propanol (10 mL) (2.12 mL, 27.0 25 mm 〇l) solution was added to 2-propanol (2E)-3-(4-chlorophenyl)_2-propenamine (1 〇rg Chem 1982 in 1 〇〇mU) at ambient temperature. 73 201204254 =5::·Γ:27_υ solution, and the mixture was stirred overnight. Concentrate the mixture and dissolve the residue in B guess (250 mL) into triethylamine (7.5 mL, 54 mm〇1) And the mixture was cooled and concentrated. The residue was treated with saturated aqueous sodium sulphate and extracted with dichloromethane (2 EtOAc). And </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> D5 4H)5 6.46 (d, 1H)3 6.12 (dt, 1H), 4.48 (quintet, 1H), 3.69 (m, 2H), 3. 23 (dd5 2H), 2 95 (m, 2H) ° 5 10 Step B: l-[(2E)-3-(4-Phenylphenyl)_2_propylene-2-nitrophenoxy) Preparation of sodium hydride (60% in oil '59 mg, 1.49 mmol) at ambient temperature to 1 [(2E)-3-(4) in N,N-dimethylformamide (5 mL) - gas phenyl) 2 · propyl] -3- 吖 11 danyl alcohol (ie the product of step a) (301 mg, 1 35 mmol) solution. After stirring for 5 minutes 'add 1, 2 - 2 _ 4 _Fluoro-5-nitrobenzene (213 μί, 1.62 mmol) and the mixture was stirred at ambient temperature overnight. The mixture was diluted with ethyl acetate and washed with water (3x) and organic phase dried (MgS04) The residue was purified by EtOAc EtOAc EtOAc (EtOAc) s, 1H), 7.28 (AB pair of d, 4H), 6.90 (s, 1H), 6.50 (d, 1H), 6.13 (dt, 1H)? 4.88 (quintet, 1H), 3.89 (m, 2H), 3.32 (dd, 2H), 3.24 (m, 2H). 5 Step C: 4,5-Dichloro-2-[[1-[(2 ugly)-3-(4-chlorophenyl)-2-propen-1-yl]-3-azetidinyl]oxy] Preparation of aniline 1-[(2Ε)-3-(4-chlorophenyl)-2-propan-1-yl]-3-(4, in ethanol-water (9:1,10 mL by volume) a solution of 5-dichloro-2-nitrophenoxy) σ丫0 denier (ie the product of the step oxime) (0.13 g, 0.31 mmol), with ammonium chloride (10 mg, 0.19 mmol) and iron Powder (10 μιη ;

176 mg, 3.1 mmol) and the mixture was heated at reflux for 30 minutes, cooled and filtered through a Celite®. The Celite® was rinsed with dichloromethane and the threshed filtrate was washed with water. The aqueous phase was extracted with dichloromethane and the combined organic extracts were dried (MgSO4) and concentrated. The residue was purified by EtOAc (EtOAc:EtOAc:EtOAc g). NMR δ 7.28 (m, 4Η), 6.77 (d, 1H), 6.54 (d5 1H), 6.50 (m, 1H), 6.14 (m, 1H), 4.78 (m, 1H), 3.90-3.81 (m, 4H) ), 2〇3.31 (m, 2H), 3_22 (m, 2H). Step D: 2-Chloro-N-[4,5-dichloro-2-[[l-[(2E)-3-(4-chlorophenyl)-2-propan-1-yl]-3- Preparation of σ丫丁基基]oxy]phenyl]-4·pyridine carboxamide 25 4,5-diqi-2-[[1-[(2£)-3-(4-phenylene) -2-propen-1-yl]-3·azetidyl]oxy]phenylamine (ie the product of Step C) (101 mg, 0.26 75 201204254

Diluted daily, washed with water (3 Torr), and the residue was purified by chromatography (EtOAc, 1% EtOAc / EtOAc EtOAc / EtOAc EtOAc The title product (97 mg) (compound of the invention) was obtained as an orange solid. night. The reaction mixture was dried (MgS 〇 4) and concentrated 4 &gt; iMR δ 8.65 (s, 1H), 8.59 (d, 1H), 8.47 (br s, 1H), 7.78 (s, 1H), 7.63 (d , 1H), 7.27 (s, 4H), 6.75 (s, 1H), 6.49 (d, 1H), 6.12 (m, 1H), 4.87 (m, 1H), 3.80 (m, 2H), 3.35-3.29 ( m, ffi). Synthesis Example 3 2-Gas-N-[4,5-dioxa-2-[[l-[(2E)-3-(4-chlorophenyl)-2-propenyl-l-yl]_3_azetidinyl] Preparation of oxalate]-4-pyridylcarboxamide (Compound 3) Oxalate 20 2-Gas-N-[4,5-di-gas-2-[2- in methane (3 mL) [1-[(2Ε)-3·(4-chlorophenyl)-2-propen-1-yl]-3-azetidinyl]oxy]phenyl]-4-pyridinecarboxamide (ie Example 2 The product (56 mg, 0.11 mmol) solution was treated with a solution of oxalic acid (4 8 mg, 53 μηιοί) in ethanol (100 s), followed by concentration and trituration with an ethyl bond to give the title of 25 light brown solids. Acid product (29 mg) (combination of the invention)

S 76 201204254 lU NMR (DMSO-d6) δ 10.23 (br s, 1H), 8.63 (d, 1H), 8.06 (s, 1H), 7.97 (s, 1H), 7.87 (d, 1H), 7.47 (d , 2H), 7.40 (d, 2H), 7.24 (s, 1H), 6.71 (d5 1H), 6.28 (m, 1H)? 5.12 (br s, 1H), 4.31 (br s, 2H), 3_82 (br s, 2H), 3.73 (br d, 2H). 5 Synthesis Example 4 2. Gas-N_[5-chloro-2·[[Η(2Ε)-3-(4-carbophenyl)-2-propen-1-yl]-3-. Preparation of azetidinyloxy]-3-pyridyl]-4·•pyridine carboxamide (Compound 16) Step A: 3·[(5-Ga-3-nitro-2-pyridyl)oxy] Preparation of -1-indolecarboxylic acid ίο 1,1-dimethylethyl ester in THF (100 mL) of 5-chloro-3-nitro-2(1Η)-pyridone (3.51 g, 20·) 1 mmol), 1,1-dimercaptoethyl 3-hydroxy-1-indolecarboxylate (3.48 g, 20.1 mmol) and triphenylphosphine (5.27 g, 24.1 mmol), added at 0 °C 1,2-bis(1-methyl15-ethyl) azodicarboxylate (4.67 mL, 24_1 mmol), and the mixture was slowly warmed to ambient temperature overnight. The mixture was then concentrated under reduced pressure and purified with EtOAc EtOAcjjjjjjj 'H NMR δ 8.32 (m5 2Η), 5.42 (m, 1H), 4.35 (dd, 2H), 4.06 2 〇 (dd, 2H), 1.45 (s, 9H). Step B: Preparation of 3-[(3-amino-5-chloro-2-pyridyl)oxy]-i-indolecarboxylic acid U-dimethylethyl ester for ethanol (45 mL) and water 3_[(5_Gas-3-Synthocyl25-yl-2-pyridyl)oxy]-1-indenyl carboxylic acid 1,1-didecylethyl ester in (5 mL) (ie step Α (4.78 g ' 14.5 mmol) solution, to which 77 201204254 ammonium chloride (46611^, 8_7 111111〇1) and iron powder (4 〇, 812§, 145 mmol) were added, and then the mixture was heated under reflux. hour. The cooled mixture was diluted with a gas-fired product and filtered through a pad of Celite® 5 vine soil filter pad, and extracted with di-methane. The filtrate was washed with water, dried (MgSO.sub.4) and concentrated. The residue was filtered through EtOAc EtOAc (EtOAc)EtOAc. lU NMR δ 7.43 (d5 1H), 6.89 (d, 1H), 5.31 (m, 1H), 4.33 (dd, 2H), 3.98 (dd, 2H), 3.89 (br s, 2H), 1.45 (s, 9H ° 10 Step C · 3·[[5-gas_3_[[(2_气_4_.pyridyl)carbonyl]amino]_2_pyridyl]oxy]-1-吖 叛 叛 1 1 , 丨_Dimethylethyl ester preparation of 3-[(3-amino-5-a-2-pyridyl15-yl)oxy]·1_% 绫 绫 in 1-gas 曱(2〇mL) 1,1-Dimercaptoethyl ester (ie product of Step B) (1.80 g, 60 〇1) and triethylamine (1.25 mL, 9.0 mmol) solution in which 2-gas-4- Pyridine carbonyl vapor (0.79 mL, 6.6 mm^l)' and the reaction was stirred overnight at ambient temperature. Saturated carbonated water = aqueous solution was added and the mixture was extracted with dichloromethane (2 Torr). The combined extracts were dried (MgSO.sub.4) and EtOAc (EtOAc)彳, lH NMR δ 8 80 (d, 1H), 8·64 (d, 1H), 8.22 (br s, 1H), 7.85 (d, 1H), 7 77 (d, out), 7.60 (dd, 1Η) ), 5.39 (m, 1H), 4 39 25 (dd, 2H), 4 01 (dd, 2H), 1.45 (s, 9H).

78 201204254 Step D: 2-Chloro-N-[5-Gas-2-[[1-[(2Ε)-3-(4-Phenylphenyl)-2-propen-1-yl]-3-indolyl) ]oxy]-3-. Preparation of pyridyl]-4-pyridinecarboxamide The treatment of 3-[[5-5 gas-3-[[(2-chloro-4-)) with hydrogenated hydrogen (5-6N in isopropanol, 10 mL) Acridine)carbonyl]amino]-2-oxaridinyloxy] U-dimethylethyl sulfonate (product of step C) (0.45 g), and vigorously stirred mixture 1 hour. Di-hydrogen methane (10 mL) was added and the mixture was stirred at ambient temperature overnight. The reaction mixture was concentrated in vacuo,qqqqq eluted The combined organic phases were dried (MgSO4) and concentrated in vacuo to give N-[2-(3-[&quot;&quot;&quot;&quot;&gt; The product of the carboxamide as a white solid (0.18 g, ca. 50% purity) was used directly without further purification. In the sample of this material (85 11^), add (2£)-3-(4-carbophenyl)-2-propenal (5〇1^, 15 0.30 mmol), triethylenesulfonate Sodium hydride (64 mg, 0-30 mmol), THF (3 mL) and EtOAc (EtOAc) The mixture was treated with saturated aqueous sodium bicarbonate and extracted with dichloromethane (2 EtOAc). The combined organic phases were dried (MgS04) and the residue was purified by chromatography (EtOAc, EtOAc (EtOAc: EtOAc middle

Purification of Et2NH) gave the title product (a compound of the invention, 29 mg). lU NMR δ 8.77 (d, 1H), 8.62 (d, 1H), 8.37 (br s, 1H)5 7.84 (d, 1H), 7.78 (s, 1H), 7.63 (dd, 1H), 7.28 (s, 4H), 6.50 (d, 25 1H), 6.14 (dt, 1H), 5.34 (m, 1H), 3.83 (m, 2H), 3.35-3.30 (m, 4H). 79 201204254 Synthesis Example 5 N-[2-[[l-[2-(4-Bromophenoxy)ethyl]-3-azetidinyl]oxy]_56-mono-3-pyridyl]-2- gas- Preparation of 4-pyridinecarboxamide (Compound 8〇) Step A: Η(3·Amino·5,6·二气_2_0 咬 咬) Oxygen h-denidic acid 1,1- fluorenyl B Preparation of base vinegar for H (3_Amine·5_gas&gt; than methoxyl group) in DMF (20 mL) (1, dimethylidene) , a solution of the product of Step B) (1.3 g, 4_34 mmol), to which was added n- s y ytamine ( 608 mg, 4.56 mmol), and the mixture was stirred overnight at ambient temperature. Dilute, dilute with water, first wash and dry (MgS〇4) 'and the concentrated residue is purified by chromatography (gelatin, 10% to 30% ethyl acetate in hexane) to obtain ^ The title product (0.85 g) was obtained as an orange foam. 15 'H NMR δ 6.99 (s5 1Η) 5 5.32 (m, 1Η), 4.35 (dd5 2H), 3.98 (dd, 2H), 3.88 (br s, 2H), 1.45 (s, 9H). Step B: 3-[[5,6-Dimethyl-3-[[(2-chloro-4.)-yl)]amino]-2-. Preparation of methoxy,-1-σγα-denidic acid ι,ι·dimethyl 2-indenyl ester of 3-[(3-amino-5,] in a gas-fired (20 mL) 6-two gas_2_

0 ratio. Alkyl)oxy]-1-.丫 旦 旦 叛 叛 1 1,1-dimercaptoethyl vinegar (ie the product of step A) (〇 · 85 g, 2.54 mmol) and triethylamine (531 μΐ ^, 3.81 mmol) solution, adding 2- Chloro-4-pyridinecarbonyl vapor (0.36 25 mL, 2 - 54 mmol), and the mixture was stirred at ambient temperature overnight. Water was added and the mixture was extracted with di-methane (2 Torr). Drying

S 80 201204254 and the extract (MgS04), and the concentrated residue was purified by chromatography (gelatin, 10% to 40% ethyl acetate in hexane) to give a yellow foam. The title product (0-9 g) was obtained as a light brown solid. 5 ^ NMR δ 8.91 (s, 1H) 5 8.64 (d, 1H), 8.14 (s, 1H), 7.76 (d, 1H), 7.60 (dd5 1H), 5.41 (m5 1H), 4.42 (dd, 2H) , 4.03 (dd, 2H), 1.46 (s, 9H). Step C: Preparation of N-[2-(3-n丫-thoxyoxy)_5,6-diox_3-pyridyl]_2-chloro 10 -4-pyridinecarboxamide in di-methane (36 mL) 3_[[5,6_Digas-3-[[(2-)-4-pyridyl)carbonyl]amino]-2-pyridyl]oxy]-1-indolecarboxylic acid l,l- A solution of dimethylethyl ester (i.e., the product of Step B) (〇·85 g), to which was added hydrobromic acid (48° / hydrazine aqueous solution, 1.8 mL), and the mixture was vigorously stirred for 15 minutes. The supernatant was decanted and the residue was carefully taken up in saturated aqueous sodium bicarbonate. The mixture was filtered, and the title compound was obtainedjjjjjjjj 4 NMR (acetone-d6) δ 8·76 (s, 1H), 8.61 (d, 1H), 7.91 (br s, 1H), 7.87 (br s5 1H), 5.18 (br s), 3.66 (br s, 2H), 3.34 (br s, 2〇2H). Step D: N-[2-[[l-[2-(4-oxaphenoxy)ethyl]_3_azetidinyl]oxy]-5,6-one gas-3-° ratio bite base-2 - Gas -4-° ratio α 定 叛 酿 的 的 的 将 将 将 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( Base two gas. 定基]·2· 氯比 bite 201204254 Carboxyguanidamine (ie the product of step C) (100 mg, 0.28 mmol) and hydrazine, hydrazine diisopropylethylamine (76 mL, 0.42 mmol) The mixture was heated in EtOAc (3 mL). It was then filtered through a column containing Celite 8 diatomaceous earth filter aid and extracted with di-methane. The residue after purification was purified by chromatography (gelatin, ethyl acetate to 5% decyl alcohol in ethyl acetate). The title product (the compound of the invention) (84 mg) was obtained as a pale yellow oil. ίο !H NMR δ 8.88 (s5 1H), 8.62 (d, 1H), 8.28 (br s, 1H), 7.77 (d, 1H), 7.62 (d, 1H), 7.37 (d, 2H), 6_78 (d, 2H), 5.35 (m, 1H), 3.99 (t, 2H), 3 .92 (t, 2H), 3.42 (br s, 2H), 2.95 (t, 2H). 15 Synthesis Example 6 2-Gas-N-[6-Gas-2-[[l_[(2E)-3_( Preparation of 4-oxophenyl)-1methyl-2-propen-1-yl]-3-azetidinyl]oxy]-3--pyridinyl]-4-acridinecarboxamide (Compound 17) Step A. 3·[(6-Gas-3-Gentocyl-2-α is hydrazinyl))]]- 〇丫α-D-Weric acid Preparation of 1,1,1-dimethylethyl ester p-toluene (20 mL) 1,1-Dimethylethyl 3-hydroxy-1-indolecarboxylic acid (1.0 g, 5.78 mmol) and 2,6-dioxa-3-nitroindole (1.12 g' 5.78 mmol) The solution, to which solid sodium hydroxide was added, and the mixture was stirred overnight at ambient temperature. The mixture was diluted with diethyl ether, washed with water and dried (MgS 〇 4). by chromatography (Shixi gum, 5% to

The title compound (1.21 g) was obtained. [H NMR δ 8.32 (d, 1 Η), 7.10 (d, 1H), 5.46 (m, 1H), 4.38 (dd, 2H), 4.08 (dd, 2H), 1.46 (s, 9H). 5 Step B: 3-[[6-Chloro-3-[[(2-chloro-4"pyridinyl)carbonyl]amino]-2_. Preparation of 1,1-dimethylethyl ester of pyridyl]oxy]_1_ oxime carboxylic acid ίο 3-[(6-) in a mixture of ethanol and water (9: 1,25 mL by volume) Nitro-3--3--2-pyrene.1,1-dimercaptoethyl vinegar (ie the product of the step oxime) (1.21 g, 3.67 mmol) To the solution, chlorinated (118 mg, 2.20 mmol) and iron powder (40 μm, 2.06 g, 36.7 mmol) were added, and the mixture was heated under reflux for 1.5 hours. The cooled mixture was diluted with dichloromethane and filtered over a pad of Celite® 15 EtOAc. The filtrate was washed with water, dried (MgSO4) and concentrated. Toluene was added and the resulting solution was concentrated again in vacuo. Dissolving the residue containing 1,1-dimercaptoethyl 3-((3-amino-6-gas-2-10 octyl)oxy]-1-indolecarboxylate in di-methane (35 mL) was added triethylamine (0.77 mL, 5.50 2 mmol) and 2-chloro-4·0 ratio (0.48 mL, 4.04 mmol). The reaction was stirred overnight at ambient temperature. Water was added and the mixture was extracted with dichloromethane (2 Torr). The combined extracts were dried (M.sub.4). EtOAc (EtOAc) 83 201204254 1HNMR5 8.70(d,1H), 8.63 (d, 1H), 8.17 (s,1H), 7.77 (d, 1H), 7.60 (dd, 1H), 7.04 (d, 1H), 5.43 (m, 1H) ), 4.42 (dd5 2H), 4.03 (dd, 2H), 1·46 (s, 9H). 5 Step C. Preparation of N-[2-(3-indolyl sigma-oxy)-6-gas-3_α ratio 0-butyl]-2_chloro-4-α-pyridinium carboxamide bis-dioxane ( 3-[[6-Chloro-3-[[(2)--4-indolyl)carbonyl]amino]-2-pyridyl]oxy]-1-indolecarboxylic acid 1 in 50 mL) A solution of 1-dimethylethyl ester (i.e., the product of Step B) (1.95 g), which was then added to hydrobromic acid (48% aqueous solution, 4.45 mL), and the mixture was stirred vigorously for 15 minutes. The supernatant was decanted and the residue was carefully neutralized with saturated aqueous sodium bicarbonate. The combined aqueous extracts were dried (MgS04) and concentrated to give the title product (1.08 g, approximately is 90% purity), which was obtained by sequentially extracting the aqueous phase with 10% by volume of methanol and dichloromethane (4 χ) in di-methane. Used directly in the next step without further purification. lU NMR δ 8.68 (d, 1H), 8.61 (d, 1H), 8.30 (s, 1H), 7.78 (d, 1H), 7.63 (dd, 1H), 7.00 (d, 1H), 5.59 (m, 1H) ), 4.10 (dd, 2H), 3.78 (dd, 2H). 20 Step D: 2-Gas-N-[6-Chloro-2_[[l-[(2E)-3-(4-chlorophenyl)·1·decyl_2_propyl-1-yl]- Preparation of 3 -α 丫 σ 定 ] ] 氧基 氧基 氧基 氧基 ] ] ] ] ] ] [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ a solution of carboxyguanamine (ie, the product of Step C) (79 mg, 0.23 mmol), to which (3E)-4-(4-chlorophenyl)-3- Buten-2-one (48 mg,

S 84 201204254 0.28 mmol ), triethyl ethoxylate (57 mg' 0.28 mmol), THF (3 mL) and acetic acid (16 pL), and the mixture was stirred overnight at ambient temperature. The mixture was treated with saturated aqueous sodium bicarbonate and extracted with dichloromethane (2 EtOAc). The combined organic phases were dried (MgS04), 5 and the concentrated residue was purified by chromatography (EtOAc, 30% ethyl acetate in hexanes (1% Et2NH) to 1% in ethyl acetate Purification of Et2NH) gave the title product (the compound of the invention) (21 mg). [H NMR δ 8.66 (d, 1H), 8.61 (d, 1H), 8.31 (br s, 1H)5 7.78 ίο (d, 1H), 7.63 (dd, 1H), 7.28 (s, 4H), 7.00 ( D5 1H), 6.48 (d, 1H), 6.01 (dd, 1H), 5.31 (m, 1H), 3.78 (m, 2H), 3.31 (m5 2H), 3.01 (m, 1H), 1.16 (d, 3H ). Synthesis Example 7 15 N-[6-Amino-5-gas-2-[[l-[(2E)-3-(4-)-phenylphenyl)-2-propan-1-yl]-3-° Azetidinyloxy]-3-ylpyridinyl]-2-chloro-4-. Preparation of Bipyridyl Carboxamide (Compound 92) Step A · 3-Gas-2,6-Diox-5-Tridentyl α Ratio α Prepared for fuming nitric acid (density 1.5 g/mL, 40 mL) 3-Chloro-2-indole-2,6-difluoro. More than a bite (4.94 g, 33.0 mmol) solution, to which sulfuric acid (30 mL) was added dropwise. The temperature of the reaction mixture rose to 38 °C. The mixture was then heated at 60 ° C for 1.5 hours, cooled on ice and extracted with hexane (2 Torr). The hexane extract was concentrated to give the title compound (3.7 g). The aqueous layer was extracted with di-methane, then dried (MgSO.sub.4) and concentrated to afford additional product (2.45 g). 85 201204254 , HNMR 5"Ut,m). Step B: 〇r '[(5-Ga-6-fluoroshawyl-2-° ratio octyl)oxy]_1_0丫σdonic acid 1,1-dimethyl Preparation of the base ethyl group _ 3's meryl pyridine (ie the product of step a) jiangsheng g, 1.5 equivalents) was combined in toluene (5 ° mL), and the mixture was stirred overnight at ambient temperature Then dilute with ether = mouth: wash the strip with water (3x) and dry (Mgs 〇 4). Purify the concentrated residue by layer: gel 5% to 15% ethyl acetate in hexane The title product (G.68 g, 8 % purity) was obtained, which can be used in the next step without further purification. 咕 δ 8.56 (d, 1H), 5 39 (m, 1H), 4 % (9) , 2H), 4 〇8 (m, 2H), 1.45 (s, 9H). 15 v-CH [6-amino-5-gas-3-[[(2-chloro-4.) than bite) Preparation of 1,1-dimercaptoethyl ester of carbyl]amino]_2_〇pyridinyl]oxy]_1_吖~d carboxylic acid '6 gas IT butanol (18 mL) and water (Μ) 3-[(5_氯=_3·吨基和比咬基)oxy]小十旦峡仏二乙乙Π Step B) (〇.68g) mixture, which is iron powder (4 〇叩, ^ and chlorination record (63%, 118 with. 'The resulting mixture is heated under reflux for 5 。 minutes. Will be fined = 细 物 物 物 物 物 物 物 释 释 释 释 C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C Dissolve the residue in the heart: re-t 25 201204254. Re-dissolve the residue in dioxane (20 mL) and add 4-(dimethylamino) bite (24 mg '0.20 mmol), Triethylamine (0.68 mL '4.9 mmol) and 2-gas-4-pyridinecarbonyl vapor (500 mg). The mixture was stirred at ambient temperature for 3 days, then treated with 1N aqueous sodium hydroxide solution. The mixture is separated, dried (MgS04) and the organic phase is concentrated. The compound in the residue is separated by chromatography (EtOAc EtOAc (EtOAc: EtOAc) [[5-Chloro-3-[[(2.sup.4-pyridyl)carbonyl]amino]]6-fluoro-2-pyridyl]oxy]-1-indole. Ethyl ethyl ester (〇37 g) and the title product (0_16 g). lH NMR δ 8.59 (d5 1H), 8.56 (s, 1H), 7.92 (br s, 1H), 7.74 (s, 1H), 7.59 (dd,1H), 5.29 (m,1H), 4.67 (br s, 2H), 4.34 (dd, 2H), 4.0 0 (dd5 2H), 1.45 (s, 9H) 〇15 Step D: N-[6-Amino-2-(1-indoleoxy)_5_chloro-3-pyridyl]-2- gas-4 -Preparation of pyridine carboxamide to 3-[[6-amino-5-chloro-3-[[(2-chloro-4 - °)pyridyl)]amine in di-methane (7 mL) The base]_ 2 _ α is smaller than the bite base] gas base].丫 旦 羧酸 carboxylic acid u-dimercaptoethyl ester (ie product of step c) (〇 16g) solution, 20 added hydrobromic acid (48% aqueous solution, 0.35 mL), and the resulting mixture at ambient temperature Stir for 15 minutes. The organic phase was decanted and the residue was treated with saturated aqueous sodium bicarbonate. The aqueous phase was extracted with 10% methanol in a methane (2x). The combined extracts were dried (MgSO4) elute 87 201204254 NMR (DMSO-d6) δ 9·97 (br s,1H),8_61 (d, 1Η),7·94 (s,1H), 7.84 (dd5 1H), 7.69 (s,1H),6.26 ( Br s,23⁄4 5.22 (m,1H), 3.74 (t, 2H), 3·52 (t,2H). 5 Step E: N-[6-Amino-5-chloro-2-[[1-[ (2e)_3_(4_Phenylphenyl)_2_ propylene-1·yl]-3-azetidinyl]oxy]_3_.pyridinyl]_2_chloro-4-pyridiniumcarboxamide Preparation in THF (3mL) N-[6-Amino-2-(Busoximeoxy)_5_Ga-3-indole]-2-gas·4-π ratio bitten amide (ie the product of the step )) (57 10 Mg, 0·16 mmol) solution, 3-(4-phenylphenyl)_2-acrolein (32 mg '1.2 ali), diethyl ethoxy sulfonate (41 mg, 12 equivalents) Treated with acetic acid (11 μί, 1.2 eq.), and the resulting mixture was stirred overnight at ambient temperature. The mixture was treated with 1N aqueous sodium hydroxide and then extracted with di-methane (2 EtOAc). Mgs〇4) 'and by chromatography (Shixi gum, EtOAc to 5% at

The concentrated residue was purified to give the title compound (the compound of the invention) (17 mg). NMR δ 8.58 (d, 1 Η), 8.55 (s, 1H), 7.98 (br s5 1H), 7.74 (s, 1H), 7.60 (d, 1H), 7.28 (s, 4H), 6.49 (dt, 1H) , 6.14 (dt, 20 1H), 5.23 (m, 1H), 4.63 (br s, 2H), 3.82 (m, 2H), 3.31 (d, 2H), 3.25 (m, 2H). Synthesis Example 8 2-Gas-N-[6-chloro-3-[[1-[(2Ε)·3-(4-Phenylphenyl)-2-propen-1-yl]_3·吖丁25 pyridine Preparation of oxy]-4-oxime [mouth + well] group]-4-pyridine carboxamide (Compound 96)

S 88 201204254 Step A: 3-[(4-Amino-6-chloro-3-σ荅[口+井]基) gas base] • Preparation of U-dimethylethyl carboxylic acid ester to DMF a solution of 1,1-dimethylethyl 3-light oxime carboxylic acid ester (3·8 g, 22.0 mmol) in (100 mL) with sodium hydride 5 (60 ° / 〇 in oil' Treated with 805 mg, 18.3 mmol) and the resulting mixture was stirred at ambient temperature for 10 min. 3,6-Dichloro-4-tower [D + well]amine (3.0 g, 18.3 mmol) was added and the mixture was taken at 9 ° C overnight. The cooled mixture was diluted with ethyl acetate and washed with water (3x), water, and dried (MgS?). The title compound (1.6 g) was obtained from mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj咕NMR (acetone-d6) δ 6.71 (s, 1H), 6.18 (br s, 2H), 5.46 (m 1H), 4.32 (br m, 2H), 3.95 (m, 2H), 1.42 (s, 9H) 〇15 Step B: 3-[[6-Gas-4-[[(2-)-4-pyridyl)carbonyl]amino][]]]]]]]]]]]]]] ,1_Dimethylethyl ester preparation River Yi milk T play, called, RV 1, decaamine oxime + gas _3_ 嗒 [mouth 20 + well] based) oxy]-1-decyl carboxylic acid U - Dimethylethyl (i.e., the product of Step A) (1.55 g ' 5.16 mmol): a liquid, which was bitten with 4-dimethylamine (63 mg, 〇·1 equivalent), triethylamine ( 2 15 rainbow, 3 equivalents) and 2_gas_4_吼 money base gas (g) were treated, and the mixture was stirred overnight at ambient temperature, 丨N aqueous sodium hydroxide solution 'and mixed. The mixture was mixed for 1 minute and then extracted with 2 gas (2x). The combined organic phases were dried (MgS〇4) and the concentrated residue was obtained by chromatography 89 25 201204254 (gelatin, gradient 30% to 60% acetonitrile in hexane). Titled person's yellow solid, 1.4 (1H), 7.77 2H) 5 4.07 5 10 15 20 iH NMR δ 8.67 (d, 1H), 8.56 (s, 1H), 8.43 (br s (m) , 1H), 7.61 (dd, 1H), 5.59 (m, 1H), 4.46 (dd (m, 2H), 1.45 (s, 9H). ' Step C: N-[3-(3-. Base H-gas _4_嗒 [Preparation of D + chloro-4-pyridinecarboxamide] 3·[[6-acridine-based] amidino-pyrene in di-methane (60 mL) [mouth + well] base] oxy] small 0 丫. day = ^ ° than dimethyl ethyl ester (ie the product of step B) (1 36g, acid U-solution, which is 氲 bromic acid (48% Aqueous solution, 3 丨miy mm〇l) The resulting mixture was stirred at ambient temperature for 15 minutes. Treatment was carried out and the residue was treated with saturated aqueous sodium bicarbonate. The organic phase was poured, washed with water and dried in vacuo. To obtain the title of the towel NMR (DMSO_d6) δ 8.51 (s, 1H), 8.38 k im, ,, 1H), 7.96 (s 1H), 7.91 (s, 1H ), 5.43 (m, 1H), 4.28 (t, 2H) 4 〇 2 2H) ° 5 Step D: 2-Chloro-N-[6-chloro-3-[[l-[(2E)-3_(4 _ gas phenyl) 2 - propylene-1-yl]-3-e 丫 α 定 ] ] 氧基 氧基 氧基 氧基 氧基 井 井 井 井 井 井 井 井 在 在 在 在 在 在 在 在N-[3-(3-吖ηdyloxy)_6_chloro_4_ 荅 [mouth + well] group] in the mL)] 2- gas-4-pyridine carboxamide (ie the product of step c) Χ110 90

S 201204254 mg, 0.32 mmol), 3-(4-phenylphenyl)-2-propanthene (65 mg, 1.2 eq.), sodium triethyloxy borohydride (82 mg, 1.2 eq.) Treatment with acetic acid (22 μί, 1.2 eq.) and the resulting mixture was stirred at ambient temperature overnight. The mixture was treated with a 1 NaOH solution of sodium hydroxide and then extracted with dichloromethane (2 EtOAc). The organic phase was dried (M.sub.3) and the title compound was purified eluting eluting (44 mg). lU NMR δ 8.65 (d, 1Η), 8.53 (br s, 2H), 7.78 (s, 1H), 7.63 i〇(dd, 1H), 7.28 (s, 4H), 6.50 (d, 1H), 6.13 ( Dt, 1H), 5.55 (m, 1H), 3.85 (m, 2H), 3.43 (dd, 2H), 3.34 (d, 2H). The compounds of Tables 1 to 118 below can be prepared by the processes described herein and by conventional methods in the art. The following are abbreviations used in the following tables: Me represents a methyl group, and Et represents an ethyl group. Used to describe the dash ("-") of the 15th generation base (for example: (R3)n or 氓13). ) represents a substituent that does not exist. Table 1

3 20 2 201204254 A1 is CH; R2 is Η; R1C is H; (R14)a is 2-C1; s is 1; and t is 1 ° R8 R9 R22 R8 R9 R22 R8 R9 R22 FF Cl FF Br FFHFH Cl FH Br FHHHF Cl HF Br HFHH Cl Cl H Cl Br H Cl HH Br Cl H Br Br H Br H Cl H Cl Cl H Br Cl HH Cl Cl Cl Cl Cl Cl Cl Cl H Cl cf3 Cl Cl cf3 Br Cl cf3 HF cf3 Cl F cf3 Br F cf3 H Br cf3 Cl Br cf3 Br Br cf3 HH cf3 Cl H cf3 Br H cf3 H Cl F Cl Cl F Br Cl FH cf3 H Cl cf3 H Br cf3 HH Br F Cl Br F Br Br FH Br Cl Cl Br Cl Br Br Cl H cf3 Cl Cl cf3 Cl Br cf3 Cl H cf3 F Cl cf3 F Br cf3 FH Cl Br Cl Cl Br Br Cl Br HFFFFF cf3 FF cf3o FHFFH cf3 FH cf3o HFFHF cf3 HF cf3o H Cl FH Cl cf3 H Cl Cf3o H Br FH Br cf3 H Br cf3o Cl HF Cl H cf3 Cl H cf3o Cl Cl F Cl Cl cf3 Cl Cl cf3o Cl cf3 F Cl cf3 cf3 Cl cf3 cf3o F cf3 FF cf3 cf3 F cf3 cf3o Br cf3 F Br cf3 cf3 Br Cf3 cf3o H cf3 FH cf3 cf3 H cf3 cf3o Cl FF Cl F cf3 Cl F cf3o 92 201204254

A1 is CH; R2 is H R8 R9 — R22 cf3 H --—^ F Br FF Br Cl F cf3 Cl F cf3 FF Cl Br F R10 is H; (Ri4)a is 2_C1; H: and R8 R9 R22 r8 ' Cf3 h

Br Br CF3 cf3 Cl F Cl Cl F Br cf3 cf3 cf3 cf3 cf3

R22 CF3〇cf3〇cf3〇cf3〇cf3〇cf3〇t The contents of the disclosure also include Table 2flj3G, which will list the column headings of Table 1 (ie “A1 is CH; r2 is under iR14, from, ο, κ H, R The system Η; a ', -Cl, S system 1; and t system 1") are replaced by the column headings shown below, and are constructed in the same manner as in the above table i. For example, in Table 2, the column headings are "A1 series CH; R2 series H; &amp; 10 series H; (R, system 2, 5-di-Cl; S system 1 and t system 1), and R8, R9 and R22 is as defined in Table 1 above. Therefore, the first item in Table 2 explicitly discloses 2,5-digas-Ν-|&gt;[[1-[(2Ε)-3-(4·chlorophenyl) )-2-propenyl small group]_3_. azetidinyl]oxy]-4,5-difluorophenyl]-4_pyridinecarboxamide. Tables 3 to 30 are similar structures. 10 Table 2 3 4 5 6 9 10 ______ column heading __ A1 is R10 H; (R14)a is 2,5-di-Cl; Γ^ΐ; and t is 1 2 A1 is CH; R2 is H; R1G is H; (R14) a is 2,6-di-Cl; s is 丨; and t is 1. A1 is CH; R2 is H; R1 is H; (R14)a is 2-C1,5-F; s system!; t) A1 is CH; R2 is h; R1 is H; (R14)a is 2-C1,6-F; s is!; and t is 1. A1 is CH; R2 is H; R1Q is H; (R14)a is 2-F; s is 1; and t is 1 » A1 is CH; R2 is h; R1Q is H; (R14)a is 2-F, 5-C1; s is!; and t is A1 is CH; R2 is H; R1G is H; (R14)a is 2,5-di-F; s is 丨; and t is 1. A1 is CH; R2 is H; R1Q is H; (R14) a is 2,6-di-F; s is 1; and t Line 1. A1 is CH; R2 is H; R1Q is Cl; (R14)a is 2-C1; s is 1; and t is A1 is CH; R2 is Me; R1G is H; (R14)a is 2 -C1; s is 1; and t is 1. 93 11 201204254 Table 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 37 37 38 39 40 _ column heading _ A1 Line CH; R2 is MeOC(O)-; R1G is H; (R14)a is 2-C1; s is 1; and t is 1. A1 is CH; R2 is EtOCH2-; R1Q is H; (R14)a 2-C1; s is 1; and t is A1 is CF; R2 is H; R1G is H; (R14)a is 2-C1; s is 1; and t is 1. A1 is CH; R2 is H; R1Q is F; (R14)a is 2-C1; s is 1; and t is 1. A1 is CH; R2 is H; R1G is H; (R14)a is 2-CF3; s is 1; and t is 1. A1 is N; R2 is H; R1Q is H; (R14)a is 2-C1; s is 1; and t is 1. A1 is N; R2 is H; R10 is H; (R14)a is 2,5-di-Cl; s is 1; and t is 1. A1 is N; R2 is H; R1G is H; (R14)a is 2,6-di-Cl; s is 1; and t is 1. A1 is N; R2 is H; R1G is H; (R14)a is 2-C1,5-F; s is 1; and t is 1. A1 is N; R2 is H; R1Q is H; (R14)a is 2-C1,6-F; s is I; and t is 1. A1 is N; R2 is H; R1G is H; (R14)a is 2-F; s is 1; and t is 1. A1 is N; R2 is H; R1Q is H; (R14)a is 2-F, 5-C1; s is 1; and t is 1. A1 is N; R2 is H; R10 is H; (R14)a is 2,5-di-F; s is 1; and t is 1. A1 is N; R2 is H; R10 is H; (R14)a is 2,6-di-F; s is 1; and t is 1. A1 is N; R2 is H; R1Q is Cl; (RI4)a is 2-C1; s is 1; and t is 1. A1 is N; R2 is Me; R1Q is H; (R14)a is 2-C1; s is 1; and t is 1. A1 is N; R2 is MeOC(O)-; R1G is H; (R14)a is 2-C1; s is 1; and t is 1. A1 is N; R2 is EtOCH2-; R1Q is H; (R14)a is 2-C1; s is 1; and t is 1. A1 is N; R2 is H; R1Q is H; (R14)a is 2-CF3; s is 1; and t is 1. A1 is CH; R2 is H; R1G is H; (R14)a is 2-C1; s is 2; and t is 2. A1 is CH; R2 is H; R1Q is H; (R14)a is 2-F; s is 2; and t is 2. A1 is CH; R2 is H; R1G is H; (R14)a is 2-CF3; s is 2; and t is 2. A1 is N; R2 is H; R1Q is H; (R14)a is 2-C1; s is 2; and t is 2. A1 is N; R2 is H; R1G is H; (R14)a is 2-F; s is 2; and t is 2. A1 is N; R2 is H; R1G is H; (R14)a is 2-CF3; s is 2; and t is 2. A1 is CH; R2 is H; R1Q is H; (R14)a is 2-C1; s is 2; and t is 1. A1 is N; R2 is H; R1G is H; (R14)a is 2-C1; s is 2; and t is 1. A1 is CH; R2 is H; R1G is H; (R14)a is 2-C1; s is 3; and t is 1. A1 is N; R2 is H; R1G is H; (R14)a is 2-C1; s is 3; and t is 1. Table 41

S 94 201204254

A1 is CH; R2 is Η; R1G is Η; and (R14)a is 2-C1. R8 R9 R22 R8 R9 R22 R8 R9 R22 FF Cl FF Br FFHFH Cl FH Br FHHH Cl Cl H Cl Br H Cl H Cl H Cl Cl H Br Cl HH Cl Cl Cl Cl Cl Cl Cl Cl H Cl cf3 Cl Cl cf3 Br Cl Cf3 HF cf3 Cl F cf3 Br F cf3 H Br cf3 Cl Br cf3 Br Br cf3 HH cf3 Cl H cf3 Br H cf3 H Cl F Cl Cl F Br Cl FH cf3 H Cl cf3 H Br cf3 HH Br F Cl Br F Br Br FH Br Cl Cl Br Cl Br Br Cl H cf3 Cl Cl cf3 Cl Br cf3 Cl H cf3 F Cl cf3 F Br cf3 FH Cl Br Cl Cl Br Br Cl Br HFFFFF cf3 FF CF30 FHFFH cf3 FH CF30 H Cl FH Cl cf3 H Cl CF30 Cl HF Cl H cf3 Cl H CF30 Cl Cl F Cl Cl cf3 Cl Cl CF30 Cl cf3 F Cl cf3 cf3 Cl cf3 CF30 F cf3 FF cf3 cf3 F cf3 CF30 95 201204254

A system CH, R2 system Η; R1. Department fj ; and (rm) R8 R9 R22 Rs J

Br H Cl CF3 Br Br CF3 cf3

Cl CF3 cf3 F H F Cl Cl F Br

F F F F F F F F F F

Br H Cl CF3 Br Br cf3 cf3 Cl CF3 cf3 F H F Cl Cl F Br 2-C1 cf3 cf3 cf3 cf3 cf3 cf3 cf3 cf3 CF, R8 R9

R 22

Br H Cl CF3 Br Br CF3 cf3 Cl cf3 cf3 FHF Cl Cl F Br CF30 CF30 CF3 CF3〇CF3〇CF3O CF3〇CF3〇cf3o The present disclosure also includes Tables 42 to 70, which will be the column headings of Table 41 (ie, The Ai series CH; R Η 1() and (Rl4w") are replaced by the same columns as shown in the following table. For example, in Table 4〇, the title line is "Α系CH; R2" The system is Η; and (R14) is 25仏-G.", and the heart is as defined in Table 41 above. Therefore: The first item in Table 40 explicitly exposes 2 5_二气_Ν chlorine [1 , 1'-biphenylfluorenyl-yl)methyl]_3H-decyl]oxy]_45_dioxaphenyl]-4-pyridinecarboxamide. Tables 43 through 70 are similar architectures. Table 42 43 44 45 46 47 48 49 A1 system CH; A1 system CH; A1 system CH; A1 system CH; A1 system CH; A1 system CH; A1 system CH; A1 system CH; R2 system H; R1Q system η R2 system H; R1(&gt; is η R2 H; R1Q is η R2 system; R1Q is η R2 system; R1G is η R2 system; Rlc is η R2 system; R1Q is η R2 system; R1G is η The column heading i(R14)a is 2,5^ϊΐΓ^Γ and (R14MS 2,6-di-Cl and (R14)a are 2-C1,5-F and (R14)a is 2-C1,6- F and (R14)a are 2-F. And (R14)a is 2-F, 5-α and (R14)a is 2,5-di-F. •, and (R14)a is 2,6- di-F 〇

Cv 96 201204254 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 Column headings A1 is CH; R2 is H; R1() is Cl; and (R14)a is 2-C1. A1 is CH; R2 is Me; R1G is Η; and (R14)a is 2-C1. A1 is CH; R2 is MeOC(O)-; R1G is Η; and (R14)a is 2-α. Α1 is CH; R2 is EtOCH2-; R1G is Η; and (R14)a is 2-C1. A1 is CF; R2 is H; R1G is Η; and (R14)a is 2-C1. A1 is CH; R2 is H; R1G is F; and (R14)a is 2-C1. A1 is CH; R2 is H; R1Q is Η; and (R14)a is 2-CF3. A1 is N; R2 is H; R1G is Η; and (R14)a is 2-C1. A1 is N; R2 is H; R1() is Η; and (R14)a is 2,5-di-Cl. A1 is N; R2 is H; R10 is Η; and (R14)a is 2,6-di-Q. A1 is N; R2 is H; R1G is Η; and (R14)a is 2-C1, 5-F. A1 is N; R2 is H; R1G is Η; and (R14)a is 2-C1,6-F. A1 is N; R2 is H; R1G is Η; and (R14)a is 2-F. A1 is N; R2 is H; R1G is Η; and (R14)a is 2-F, 5-α. Α1 is Ν; R2 is Η; R10 is Η; and (R14)a is 2,5-di-F. A1 is N; R2 is H; R1Q is Η; and (R14)a is 2,6-di-F. A1 is N; R2 is H; R1G is Cl; and (R14)a is 2-C1. A1 is N; R2 is Me; R1Q is Η; and (R14)a is 2-C1. A1 is N; R2 is MeOC(O)-; R1G is Η; and (R14)a is 2-C1. A1 is N; R2 is EtOCH2-; R1G is Η; and (R14)a is 2-α. Α1 is Ν; R2 is Η; R1G is Η; and (R14)a is 2-CF3. Table 71

97 201204254 A1 (R22)b (R13)c A1 (R22)b (R13)〇A1 (R22)b (R13)〇CH 4-Cl 2-F CH 2,6-di-F, 4-Cl 2- FN 2-F, 4-Cl 2-F CH 4-C1 3-F CH 2,6-di-F, 4-Cl 3-FN 2-F, 4-Cl 3-F CH 2-F, 4- Cl — CH 4-Cl 2-Me N 2,6-di-F, 4-Cl — CH 2-F, 4-Cl 2-FN 4-Cl 2-FN 2,6-di-F, 4-Cl 2-F CH 2-F, 4-Cl 3-FN 4-Cl 3-FN 2,6-di-F, 4-Cl 3-F CH 2,6-di-F, 4-Cl — N 2- F, 4-Cl — N 4-Cl 2-Me Table 72 Ί

Α1 is CH; (R3)n is 2-Me; and R4, R11 and R12 are Η.

R8 R9 R8 R9 R8 R9 R8 R9 F F F cf3 Br Cl H F F H Br cf3 cf3 Cl H Br H Cl H cf3 cf3 F H cf3 Cl H Cl F Cl Br I H Cl Cl cf3 H H H ch3 H Cl cf3 Br F Br H cf2ho H 98 201204254

The disclosure of the present invention also includes Tables 73 to 85, and each of the ^72^(Γ Al ^ CH ; 2_^ - T and R system Η.") is replaced by the respective column headings shown below, and is the same as Table 72 above. The construction method is the same. For example, in Table 73, the column system is / Α CH; (R3) n is 3-Me; and R11 and R12 are η. And R and R9 are as defined in Table 72 above. Therefore, the first item in Table 73 explicitly discloses 2-chloro-indole [2-[[1-[(2Ε)-3-(4-carbophenyl))-2-propen-1-yl]-3-) Alkyl-3-azetidinyl]oxy]_45_difluorophenyl]Μη is a pyridinium carboxamide. Tables 74 through 85 are similar architectures. Rabbit 73 74 75 76 77 78 80 81 82 83 84 85 ______ Column heading Α1 is CH; (R3)n is 3-Me; and r4, ru and r12 are η. Α is CH, (R) η (η system ;); Me is; and Rii and ri2 are η. Α is CH, (R) η (η system ;); R4 and r12 are η; and Rii is ρ. A1 is CH; (R3)n is (n system 〇); R4 and Rii are η; and R12 is ρ. A system CH; (R) n system (n system 〇); R4 and ri2 are η; and Rii is Me. A1 is CH; (R)n is (n-system); R4 and Ri 1 are η; and ri2 is Me. A1 is N; (R3)n is 2-Me; and r4, ru and r12 are η. Α1 is N; (R3)n is 3-Me; and r4, r11 and r12 are η. Α1 is N; (R) η is '(η system 〇); r4 is Me; and R11 and R12 are η. Α1 is N; (R) η-'(η system ;); r4 and r12 are η; and Rii is f. A1 is N; (R3)n is "-'' (n system); R4 and Rii are η; and Ri2 is ρ. A1 is N; (R3)n is "-'' (n is 0); R4 And r is 2 is η; and Rii is Me. A1 is N; (R3)n is "-" (n is 0); R4 is and Rii is η; and ri2 is Me. Table 86 99 201204254

A1 is CH; (R3)n is 2-Me; and R4 is Η. R8 R9 R8 R9 R8 R9 R8 R9 FFF cf3 Br Cl HFFH Br cf3 cf3 Cl H Br Η Cl H cf3 cf3 FH cf3 Cl H Cl F Cl Br IH Cl Cl cf3 HHH ch3 H Cl cf3 Br F Br H cf2ho H The contents also include Tables 87 to 91, and each table except Table 5 replaces the column headings of Table 86 (ie, "Α1 is CH; (R3)n-series 2-Me; and R4 is Η.") with the respective columns shown below. Except for the title, it is the same as the construction of Table 86 above. For example, in Table 87, the column headings are "Α1 is CH; (R3)n is 3-Me; and R4 is Η.", and R8 and R9 are as defined in Table 86 above. Therefore, the first item in Table 87 clearly discloses that 2-chloro-indole-[4,5-difluoro-2-[[1·[(4'-fluoro[Ι,Γ-biphenyl]-4) -yl)mercapto]-3-methyl-3-azetidinyl]oxy]phenyl]-4-acridinium carboxamide. Tables 88 through 91 are similar architectures. Table 87 88 _ column heading Α1 is CH; (R3)n is 3-Me; and R4 is Η. Α1 is CH; (R3)n is "-" (η system 0); and R4 is Me. 201204254 Table 89 90 91 _ column headings A1 is N; (R3)n is 2-Me; and R4 is Η. Α1 is N; (R3)n is 3-Me; and R4 is Η. Α1 is N; (R3)n is "-" (η system 0); and R4 is Me. Table 92

A1 is CH; R34 is Η; Z is CH; s is 1; and t is 1.

R8 R9 R22 R8 R9 R22 R8 R9 R22 FF Cl FF Br FFHFH Cl FH Br FHH Η F Cl HF Br HFH Η Cl Cl H Cl Br H Cl H Η Br Cl H Br Br H Br H Cl H Cl Cl H Br Cl HH Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl Cl FH cf3 H Cl cf3 H Br cf3 HH Br F Cl Br F Br Br FH Br Cl Cl Br Cl Br Br Cl H cf3 Cl Cl cf3 Cl Br cf3 Cl H 101 201204254 A1 system CH ; R34 system Η ; Z system CH ; s Line 1; and t is 1. R8 R9 R22 R8 R9 R22 R8 R9 R22 cf3 F Cl cf3 F Br cf3 FH Cl Br Cl Cl Br Br Cl Br HFFFFF cf3 FF cf3o FHFFH cf3 FH cf3o Η FFHF cf3 HF cf3o Η Cl FH Cl cf3 H Cl cf3o Η Br FH Br Cf3 H Br cf3o Cl HF Cl H cf3 Cl H cf3o Cl Cl F Cl Cl cf3 Cl Cl cf3o Cl cf3 F Cl cf3 cf3 Cl cf3 cf3o F cf3 FF cf3 cf3 F cf3 cf3o Br cf3 F Br cf3 cf3 Br cf3 cf3o H cf3 FH Cf3 cf3 H cf3 cf3o Cl FF Cl F cf3 Cl F cf3o cf3 HF cf3 H cf3 cf3 H cf3o Br FF Br F cf3 Br F cf3o Br Cl F Br Cl cf3 Br Cl cf3o cf3 Cl F cf3 Cl cf3 cf3 Cl cf3o cf3 FF cf3 F cf3 cf3 F cf3o Cl Br F Cl Br cf3 Cl Br cf3o The present disclosure also includes Tables 93 to 110, and each table except the column heading of Table 92 (ie, "A1 system CH; R34 system Η; Z system CH ; s is 1; and t is 1. ") is replaced with the respective column headings shown below, and is constructed in the same manner as in Table 92 above. For example, in Table 93, the headings are "A1 series N; R34 system Η; Z system CH; s system 1; and t system 1", and R8, R9 and R22 are as defined in Table 92 above. Therefore, the first item in Table 93 clearly reveals 2-oxo-N-[2-[[l-[2-(4-chlorophenoxy) 201204254 ethyl]-3 -σ丫丁丁基]oxy ]_5,6-two gas _3-° than bite base] -4_atb bite retinoic acid. Tables 94 through 110 are similar architectures. Table headings 93 A1 is N; R34 is Η; Z is CH; s is 1; and t is 1. 94 A1 is CH; R34 is Me; Z is CH "s system 1; and t is 1. 95 A1 is N; R34 is Me; Z is CH; s is 1; and t is 1. 96 A1 is CH; System Η; Z system N; s system 1; and t system 1. 97 A1 system N; R34 system Z; Z system N; s system 1; and t system 1. 98 A1 system CH; R34 system Me; Z system N s is 1 and t is 1. 99 A1 is N; R34 is Me; Z is N; s is 1; and t is 1. 100 A1 is CH; R34 is Z; Z is CH; s is 2; t is 2. 101 A1 is N; R34 is Η; Z is CH; s is 2; and t is 2. 102 A1 is CH; R34 is Me; Z is CH; s is 2; and t is 2. 103 A1 Line N; R34 is Me; Z is CH; s is 2: and t is 2. 104 A1 is CH; R34 is Η; Z is CH; s is 2: and t is 1 ° 105 A1 is N; R34 is Z system CH; s system 2; and t system 1. 107 A1 system CH; R34 system Me; Z system CH [; s system 2; and t system 1. 108 A1 system N; R34 system Me; Z system CH; s system 2: and t system 1. 109 A1 system CH; R34 system Z; Z system CH; s system 3: and t system 1 ° 110 A1 system N; R34 system Me; Z system CH; s system 3: and t Department 1. Table 111

103 201204254 R22b is a 2-F; and R34 is a Η. R8 R9 R22a R8 R9 R22a R8 R9 R22a FF Cl FF Br FFHFH Cl FH Br FHHHF Cl HF Br HFHH Cl Cl H Cl Br H Cl HH Br Cl H Br Br H Br H Cl H Cl Cl H Br Cl HH Cl Cl Cl Cl Cl Br Cl Cl H Cl cf3 Cl Cl cf3 Br Cl cf3 HF cf3 Cl F cf3 Br F cf3 H Br cf3 Cl Br cf3 Br Br cf3 HH cf3 Cl H cf3 Br H cf3 H Cl F Cl Cl F Br Cl FH cf3 H Cl Cf3 H Br cf3 HH Br F Cl Br F Br Br FH Br Cl Cl Br Cl Br Br Cl H cf3 Cl Cl cf3 Cl Br cf3 Cl H cf3 F Cl cf3 F Br cf3 FH Cl Br Cl Cl Br Br Cl Br HFFFFF cf3 FF CF30 FHFFH cf3 FH CF30 HFFHF cf3 HF CF30 H Cl FH Cl cf3 H Cl CF30 H Br FH Br cf3 H Br CF30 Cl HF Cl H cf3 Cl H CF30 Cl Cl F Cl Cl cf3 Cl Cl CF30 Cl cf3 F Cl cf3 cf3 Cl cf3 CF30 F cf3 FF cf3 cf3 F cf3 CF30 Br cf3 F Br cf3 cf3 Br cf3 CF30 H cf3 FH cf3 cf3 H cf3 CF30 Cl FF Cl F cf3 Cl F CF30

S 104 201204254

R22b is 2-F; and R R8 R9 R22a cf3 ~ - H----F Br F F Br Cl F cf3 Cl F cf3 F F Cl Br F Η. R8 _ R9 R22a cf3 H cf3 Br F cf3 Br Cl cf3 cf3 Cl cf3 cf3 F cf3 Cl Br cf3 R8 R9 R22a cf3 H cf3o Br F cf3o Br Cl cf3o cf3 Cl cf3o cf3 F cf3o Cl Br cf3o The present disclosure also includes a table 112 to ιΐ4, and each table is replaced with the column heading of Table 111 (ie, "Rm system 2_F; and ruler 34 system 」."), and is replaced with the respective column headings shown below, and is constructed in the same manner as Table 111 above. the same. For example, the column headings in Table 112 are "R22b is 3_F; ^ R34 is Η."' and R8, Ruler 9, and Ruler are defined as Table U1 above. Therefore, the first item in Table 112 clearly discloses 2_chloro-N-[2-[[l-[2-(4-gas-3-fluorophenoxy)ethyl]-3·azetidinyl; Difluoro] 3-fluoropyridyl H-pyridine carboxamide. Tables 113 through 114 are similar architectures. Rabbit 112 113 114 -Γ77~~-_____ column heading ------- R22b is 3-F; and R34 is η. R22b is 2-F; and R34 is Me R22b is 3-F; and 1134 is Me Table 115 201204254

s is 1; and t is 1 〇R9 ~~ _ R14 R22 C1 Cl F C1 Cl Cl C1 Cl Br Br Cl F Br Cl Cl Br Cl Br cf3 Cl F cf3 Cl Cl cf3 Cl Br R9 R14 r22 Cl cf3 F Cl cf3 Cl Cl cf3 Br Br cf3 F Br cf3 Cl Br cf3 Br cf3 cf3 F cf3 cf3 Cl cf3 cf3 Br R9 R14 R22 Cl Br ~----- F Cl Br Cl Cl Br Br Br Br Br Br Br Br Br Br cf3 Br F cf3 Br Cl cf3 Br Br The present disclosure also includes tables 116 to 118, and each I will list the column headings of table 115 (ie, "S system 1; and t system"), replacing = respective columns shown below Except for the title, it is the same as the construction method of Table 115 above. For example, in Table 116, the column headings are rs 2; and the £ 2 is. And R9, R14 and R22 are as defined in Table 115 above. Therefore, the first item in Table 116 explicitly discloses 2_gas_N-[6_gas '3'[[1-[(2Ε)-3-(4-fluorophenyl)_2_propenyl] _4_TB pyridine base] gas base]-4-嗒 [mouth + well] base]-4-pyridine carboxamide. Tables in to 118 are similar architectures. Column heading 201204254 Table 116 117 118 Column headings s is 2; and t is 2. s is 2; and t is 1. s system 3; and t system 1 〇 formulation / utility The compound of the invention will generally be used as an active ingredient in a composition (ie formulation) for controlling invertebrate pests, accompanied by at least one selected from surfactants, solids An additional component of the group consisting of a diluent and a liquid diluent is used as a carrier. The formulation or composition ingredients are selected to match the physical properties of the active ingredient, the type of application and the environmental factors such as soil type, humidity and temperature. Useful formulations include liquid and solid compositions. Liquid compositions include solutions (including emulsions), suspensions, emulsions (including microemulsions and/or suspoemulsions), and the like, and optionally thickened to a gel. Typical types of aqueous liquid compositions are soluble concentrates, suspension concentrates, capsule suspensions, concentrated emulsions, microemulsions and suspension emulsions. Typical types of non-aqueous liquid compositions are emulsions, microemulsions, dispersible concentrates and water-dispersible oil dispersions. Typical types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, filled films (including seed coatings) And so on, it can be water dispersible ("wettable") or water soluble. Films and coatings formed from film-forming solutions or flowable suspending agents are used in seed treatments in particular for 201204254. The active ingredient can be encapsulated by (-suspension or solid formula; $-encapsulated and step-forming capsules (or "preservation of active ingredient f can or slow the release of active ingredients: wrapper"). The package can be controlled in t: (usually water). Spray _ quantity two = release 15 20 = mixed with water or other suitable medium in the tank: applied to the leaf treatment by = surface application, or the growth of the plant ^ Medium or terrane formula and dry formula can be directly measured = _ liquid system or furrow. Liquid and solid formula can be applied to the seed of the plant, as a seed treatment before sowing, he; It is protected by the roots of the development and other underground plant parts. The 5Tif towel contains (4) the effect of the lower %=: diluent and surfactant, the weight of which will add dihydrate dispersible granules and water-soluble granules. , tablets and powders, water-dispersible oil suspensions, suspensions, emulsions, solutions (including emulsions), weight percent components 0 001-90 1-50

Thinner 0-99.999 Surfactant 0-15 40-99

201204254 . Dust 1-25 70-99 0-5 Fine particles and granules 0.001-99 5-99.999 0-15 &quot; High-strength composition 90-99 〇-1〇0-2 Solid diluent includes, for example, 'like swelling Soil, microcrystalline kaolinite, eucalyptus and kaolin clay, gypsum, cellulose, titanium dioxide, zinc oxide, temple powder, dextrin, sugar (such as lactose, sucrose), dream stone, slip 5 stone, mica, 矽Algae, urea, calcium carbonate, sodium carbonate and sodium bicarbonate, and sodium sulfate. Typical solid diluents are described in the work of Watkin Seta1, Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Liquid rinsing agents include, for example, water, N,N-dimethyl decylamine (e.g., N,N-dimethyl decylamine), decene, dimethyl sulfoxide, N-alkylpyrrole An ketone (eg, N-methylpyrrolidone), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propyl carbonate, butyl carbonate, stone bad (eg, white mineral oil, Normally burned hydrocarbons, isothermal hydrocarbons, alkylated benzene, phthalic acid naphthalene, glycerol, glycerol 15 triacetate, sorbitol, aromatic hydrocarbons, dearomatized aliphatic, alkylbenzene, alkylene naphthalene, Such as cycloheximide, 2-glyoxime, isophorone and 4-keto-4-methyl-2-pentanone ketone, such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate And acetic acid vinegar of decyl acetate, tridecyl acetate and isodecyl acetate, such as alkyiated lactate ester, diester and other esters of γ-20 butyrolactone, and alcohols, which may be Linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol, decyl alcohol, Decanol, isostearyl alcohol, green soil alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, 109,201,204,254 tetrahydrofurfuryl alcohol, diacetone alcohol and benzyl alcohol Yue. Liquid diluents also include glycerides of saturated and unsaturated fatty acids (usually c6-c22), such as plant seeds and fruit oils (eg olives, ramie, linseed, sesame, corn, metabolites, Xiangri Cai, Liu Hunt', safflower, cotton stalk, soybean, rapeseed, 5 coconut and palm kernel oil), animal-derived fat (such as butter, pork fat, lard, cod liver oil, fish oil) and mixtures thereof. The liquid diluent also includes a burnt fatty acid (e.g., thiolated, ethylated, butylated), wherein the fatty acid can be obtained by hydrolyzing glycerides derived from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed', Interscience, New York, 1950. The solid and liquid compositions of the present invention typically comprise one or more surfactants. Surfactants (also known as "surfactants") typically change (and most often reduce) the surface tension of the liquid 15 when added to a liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, the surfactant can be used as a moisturizing agent, a sub-(four), an emulsifier or an antifoaming agent. Surfactants can be classified into prostagland, anionic or cationic. Herbicide surfactants useful in the present compositions, including, but not limited to: lyoalkoxy groups, such as alcohol based on natural and synthetic alcohols, which may be branched or _) by alcohol and ring milk Prepared by burning, propylene oxide, butyl oxide or a mixture thereof, adding 'amine ethoxylate, lysine and ethoxylated linaloamine; alkoxylated glycerin, such as ethoxylated soybeans , dry hemp and rapeseed 25 ' from: squid alkoxy, such as octyl phenyl, ethoxylate, sulfhydryl, ethoxylate, bis(10), ethoxylate and twelve lin Benzene, 201204254 ethoxylates, (from phenolic based oxides or mixtures thereof, (iv) oxides, butyl condensates from _oxides and reversed money polymers, terminally based fatty acids and oils Preparation = ethoxylated fatty acids; ethoxy, 4 . 夂 / by 曰, ethoxylated methyl esters; ethoxylated 惫 惫 甘 甘 including those from ethylene oxide, propylene oxide,丁死m :::mixer preparation); fatty acid esters, glycerides, flats > earthworms, polyethoxylates For example, polyethoxylated mountain 10 15 20 anhydride, H, H, polyethoxylated sorbitan fatty acid, and polyethoxylated glycerol fatty acid; other sorbitan derivatives, such as sorbitol Anhydride class 1, polymerized surfactants, such as random copolymers, block copolymers, polyethylene glycol resins, neo- or comb polymers, and star polymers; polyethylene glycols (pegs); polyethylene Alcohol fatty acid esters; polyoxynoxy base surfactants; and sugar derivatives such as sucrose esters, alkyl polyglycosides, and alkyl polysaccharides. Useful anionic surfactants, including, but not limited to, alkylaryllithoic acid and salts thereof; carboxylated or alkylphenol ethoxylates; biphenyl acid salt derivatives; lignin and lignin derivatives , for example, lignosulfonate; maleic acid or succinic acid or its anhydride; terpene hydrocarbon acid salt; phosphate esters, such as phosphate esters of alcohols, phosphate esters of alkylphenols, and styryl groups Phosphate esters of phenol ethoxylates; protein-based surfactants; creatinine derivatives; phenol ether sulfates; sulfonates and sulfates of oils and fatty acids; sulfonates of ethoxylated alkylphenols and Sulfate; sulfate of alcohol; sulfate of ethoxylated alcohol; sulfonate of amine and guanamine, such as hydrazine, decane-alkyl taurate; benzene, cumene, toluene, hydrazine, and twelve Alkylbenzenes and tridecylbenzenes; sulfonates of concentrated naphthalene; 111 25 201204254 Potassates of naphthalene and alkyl naphthalene; oil-removing acid hydrochloride; scutellaria sulphate; Acid salts and derivatives thereof, such as dialkyl sulfosuccinate salts. Useful cationic surfactants, including, but not limited to, decylamine 5 and ethoxylated decylamine; amines such as N-nonyl propylene diamine, dipropylene triamine, and dipropylene tetramine, and ethoxylate Amines, ethoxydiamines and propoxyamines (prepared from amines and ethylene oxide, propylene oxides, butyl oxides and mixtures thereof); amine salts such as amine acetic acid and diamine salts a quaternary ammonium salt such as a quaternary salt, an ethoxy quaternary salt 10 and a double quaternary salt; and an amine oxide such as dimethylamine oxide and bis-(2-hydroxyethyl)- Alkylamine oxide. Also useful in the compositions of the present invention are mixtures of nonionic surfactants with anionic surfactants, or mixtures of nonionic surfactants with cationic surfactants. Nonionic, anionic, and cationic 15 subsurfactants, as well as their use recommendations, have been disclosed in a number of published references, including McCutcheon's Emulsifiers and Detergents, annual American and International Editions published by McCutcheon's Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, 2〇Encyclopedia of Surface Active Agents, Chemical Publ.

Co., Inc., New York, 1964; and A S. Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987. The compositions of the present invention may also contain formulation aids and additives, as well as formulation auxiliaries well known in the art of 25 (some of which may also be considered to provide a function as a solid diluent, liquid diluent or surfactant). These formulas

S 112 201204254 Agents and additives may be controlled: pH (buffer solution), foaming during treatment (preventing 14 polyorganosiloxanes), deposition of active ingredients (suspension), viscosity (thixotropy) Thickener), microbial growth in the outer shell (antibacterial agent), freezing of the product (antifreeze), dyeing (dye/pigment dispersant), washing (filming agent or adhesive), evaporation (evaporation retarder) And other recipe features. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes. Examples of formulating adjuvants and additives' include those listed in \4(^1^ ratio 6011,5¥〇11»1^2: Functional Materials, annual International and North American editions published by McCutcheon^s Division, The Manufacturing Confecti 〇ner PubHshing c〇; and PCT Publication No. WO 03/024222, examples of which are generally obtained by dissolving a compound of formula 1 and any other active ingredient in a solvent, or grinding it in a liquid or dry diluent, The active ingredient is incorporated into the composition of the present invention. A liquid preparation, including an emulsion, can be prepared by simply mixing the ingredients. If the solvent of the liquid composition intended to be used as an emulsion is immiscible with water, it is usually diluted with water. An emulsifier is added to emulsify the solvent containing the active ingredient. The slurry of the active ingredient having a particle diameter of 2,000 μm is wet-ground using a media mill to obtain particles having an average diameter of 3 μηη or less. The aqueous slurry can be made into a finished product. The agent (see, for example, U_S. 3, 060, 084) or further processed into a water-dispersible granule by spray drying. The dry formulation usually requires a dry grinding process, which produces a flat The average particle diameter is in the range of 2 to 1 〇μηι. The dust and powder preparation method is blended, and usually added with grinding (such as hammer mill or liquid energy grinder). Fine particle and particle preparation methods are used to The material is sprayed onto a particulate carrier formed in Pre-113 201204254 or by cohesion technique. See Browning, “Agglomeration”, Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed_, McGraw- Hill, New York, 1963, pages 8-57 and 5, and WO 91/13546. Pellets can be prepared as described in US 4,172,714. Water-dispersible and water-soluble granules can be prepared as in US 4 And the teachings of U.S. Patent No. 5, 280, 493, the disclosure of which is incorporated herein by reference to U.S. Pat. , see TS Woods, “The Formulator's Toolbox - Product Forms for Modern Agriculture” in Pesticide Chemistry and Bio Science, The Food-Environment Challenge, T. Brooks and T ° R. is Roberts, Eds., Proceedings of the 9th International

Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. Patent No. 3,235,361, column 6, line 16 to column 7, line 19, and example 10-41; U.S. Patent No. 3,309,192, column 5, line 43 to column 20, line 62, and examples 8, 12, 15, 39, 4, 52, 53, 58, 132, 138-140, 162-164, 166, 167, and 169-182; US Patent No. 2,891,855, column 3, line 66, line 5, and examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp. 81-96; Hance et al, 25 Weed Control Handbook, 8th edition, Blackwell Scientific

Publications, Oxford, 1989; and Developments in 201204254 formulation technology, PJB Publications, Richmond, UK, 2000. In the examples below, all formulations were prepared in a conventional manner. For the compound number, refer to the compounds in the index tables A-F. Even without further elaboration, it is believed that those of ordinary skill in the art in the <RTIgt; Therefore, the following examples are for illustrative purposes only and are not intended to limit the disclosure of the invention. Unless otherwise stated, the percentages are by weight.

10 Example A High-intensity concentrate compound 1 98.5% Helium gel 0.5% Synthetic amorphous fine-grained soil Example B 1.0% Wettable powder compound 2 65.0% Dodecylphenol polyglycol ether 2.0% Sodium lignosulfonate 4.0 % 石夕铭酸纳 6.0% montmorillonite (calcined) Example C 23.0% Fine-grain compound 1 10.0% Eudragit soil fine particles (low volatile matter, 0.71/0.30 mm; Q0 0% USS No. 25-50 Sieve) 115 15 201204254

Example D Extrusion of particles Compound 2 25.0% anhydrous sodium sulfate 10.0% calcium crude lignosulfonate 5.0% sodium naphthoate 1.0% calcium/magnesium bauxite 59.0%

Example E Emulsion Compound 1 10.0% Polyoxyethylene 20.0% sorbitol hexoleate C6-C10 fatty acid oxime ester 70.0%

Example F Microemulsion Compound 2 5.0% Polyvinylpyrrolidone-ethylene acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0%

S Example G Seed treatment compound 1 20.00% polyvinylpyrrolidone-ethylene acetate copolymer 5.00% montanic acid wax 5.00% calcium lignosulfonate 1.00% polyoxyethylene/polyoxypropylene block copolymer 1.00% hard fat Alcohol (P0E 20) 2.00% Polyorganosilane 0.20% Red dye 0.05% Water 65.75% 116 201204254 Example 肥料 Fertilizer Adhesive Compound 2 2.5% Pyrrolidone-Benzene Ethylene Copolymer 4.8% Triphenylethylidene 16- Ethoxylate (tristyrylphenyl 2.3% 16-ethoxylate) talc 0.8% corn starch 5.0%

Nitrophoska® Permanent 15-9-15 Slow-acting fertilizer 36.0〇/〇 (BASF) Kaolin 38.0% Water 10.6%

Example I Wettable powder Compound 31 65.0% Dodecylphenol polyglycol ether 2.0% Sodium lignosulfonate 4.0% Sodium strontium aluminate 6.0% Montmorillonite (calcined) 23.0%

Example J Microemulsion Compound 147 5.0% Polyvinylpyrrolidone-ethylene acetate copolymer 30.0% alkylpolyglycoside 30.0% glyceryl monooleate 15.0% water 20.0% The compounds have activity against many invertebrate pests. These pests include invertebrates that inhabit different environments, such as plant leaves, roots, soil, harvested crops or other foods, or animal skin. These pests contain invertebrate seeds (leaves, stems, flowers and fruits), seeds, + # &amp; 1 , leaves only J, wood, textile fiber animal blood or tissue for food 'thus causing growth or storage of agriculture = Harmfulness of crops, forests, warm crops, ornamental crops, storage or fiber products, houses or other structures or period contents, or harmful to human animal health or public health. Those familiar with this 2 will understand that not all compounds are present for all parasites: the long-term effects are the same. 10 15 20 The compounds and compositions are useful for agronomically protecting field crops from herbivorous invertebrate pests and also protecting other horticultural crops and plants from non-farm farming from herbivores. Invertebrates & pests. This application includes the protection of crops from other plants (i.e., agronomic and non-agronomic) containing genetically engineered genetic material (meaning genetically transgenic) or genetic modification to provide favorable traits. Examples of such traits include tolerance to herbicides, resistance to herbivorous pests (eg, insects, wallworms, worms, spiders, nematodes, snails, phytopathogenic fungi, bacteria, and viruses), and improved plant growth. Increase tolerance to adverse growth conditions, such as high or low temperature, low or high soil moisture, and high salinity, increased flowering and fruiting, increased yield, faster maturity, improved quality and/or nutritional value of the harvested product or Improve the storage or handling properties of the blown product. Genetically transformed plants can be modified to exhibit a variety of traits. Examples of plants contain features provided by genetic engineering or genetic mutations, including many types of corn, cotton, soybeans and potatoes that express Bacillus thuringiensis toxins such as YIELD GARD®, KNOCKOUT®, STARLINK®, BOLLGARD ®, NuCOTN® and NEWLEAF® 'and many kinds of corn herbicides, 25 201204254 cotton 'soya and rapeseed, such as ROUNDUPREADY®, LIBERTY LINK®, IMI®, STS1 CLEARFIELD®, and the performance of Ν· acetyl-transferase (GAT) crops that provide resistance to glyphosate herbicides or crops containing HRA genes that provide resistance to herbicides that inhibit acetate lactate synthase (ALS). The compounds and compositions may interact synergistically with features obtained by genetic engineering introduction or genetic mutation modification, thereby increasing the effectiveness of phenotypic expression or characteristics, or increasing the effectiveness of the present compounds and compositions to control invertebrate pests. In particular, the compounds and compositions of the present invention may act synergistically with protein phenotypes or other natural products that are toxic to invertebrate pests to provide pest control greater than the additive effect. The composition of the present invention also optionally comprises a plant nutrient, for example, a fertilizer composition comprising at least one member selected from the group consisting of nitrogen, phosphorus, potassium, sulfur, calcium, magnesium 'iron, copper, boron, manganese, zinc and molybdenum. Plant nutrients. It is noted that the composition comprises at least one fertilizer composition comprising at least one plant nutrient selected from the group consisting of nitrogen, phosphorus, potassium, sulfur, calcium and magnesium. The composition of the present invention further comprises at least a plant nutrient which may be in the form of a liquid or a solid. It is worth noting that the solid formulation is in the form of granules, small sticks or tablets. A solid formulation comprising a fertilizer composition can be prepared by mixing the compound or composition of the present invention with a fertilizer composition together with the formulation ingredients, followed by preparation of the formulation in a manner such as granulation or extrusion. Alternatively, the solid formulation can be prepared by spraying a solution or suspension of a compound or composition of the present invention in a volatile solution onto a previously prepared fertilizer composition, and then volatilizing the solvent to produce 119 201204254 Preparation &gt; λ granules The ballast composition is in the form of a sterically stable mixture, such as: small sticks or tablets. No roll!! Agronomic use refers to the use of pest control in all areas except crop plants. The compounds and compositions of the present invention are controlled by non-agriculturally stored cereals, legumes, and invertebrate pests in fabrics such as clothing. The non-agronomic uses of the compounds of the present invention also include invertebrate pest control on the view, plants, forests, middle, roadside and railway road construction sites and on turf such as grassland, gorge and pasture. The non-agronomic uses of the S compositions and compositions of the present invention are also controlled by invertebrate pests in houses and other (four) that can be inhabited by humans and/or animals, farm animals, pasture animals, zoo animals or other animals. The non-agronomic use of the compounds and compositions of the present invention also includes the control of pests that can damage wood or other structural materials used in buildings, such as white sacrifice. The non-agronomic use of the compounds and compositions of the present invention also includes the protection of human and animal health by controlling invertebrate pests that parasitic or spread infectious diseases. Animal parasites include, inter alia, controlling ectoparasites that are parasitic on the surface of the host animal (eg, shoulders, armpits, 20 abdomen, inner thighs). Parasitic or disease-transmitting pests include, for example, ticks, ticks, ticks, mosquitoes, flies, ticks, and fleas. The compounds and compositions of the present invention are suitable for systemic and/or non-systematic control of parasites or infections in animals. The compounds and compositions of the present invention are suitable for the propagation of pests against ectoparasites or diseases. The compounds and compositions 25 of the present invention are suitable for combating parasites that infest agriculturally processed animals, such as cattle, sheep, goats, horses, pigs, donkeys, lures, buffalo, rabbits, hens, turkeys, 201204254 ducks, Goose and bees; pet animals and livestock such as dogs, cats, pet birds and ornamental fish; and so-called experimental animals such as hamsters, guinea pigs, rats and mice. By combating these parasites, mortality and efficacy are reduced (by meat, milk, wool, hide, egg, honey, etc.), as this application of a compound comprising a compound of the invention makes feeding animals more economical and simpler . Examples of agronomic and non-agronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, for example, army worms, cutworms, loopers 10 and Heliothines in Noctuidae (eg, large mold (Sesamiainferens Walker), corn fill (Sesamia nonagrioides Lefebvre), lotus night thief Insects (Spodoptera eridania Cramer), Spodoptera 15 fugiperda J. E. Smith, Spodoptera exigua Hiibner, Spodoptera litura (Spodoptera littoralis Boisduval), yellow-spotted moth (Spodoptera ornithogalli Guerre), black-cutting rootworm (Agrotis ipsilon Hufnagel), Beanworm ( Anticarsia gemmatalis Hiibner), Lithophane antennata Walker, Barathra brassicae Linnaeus, Soybean base (soybean) Pseudoplusia includens Walker), Trichoplusiani Hiibner, Heliothis virescens Fabricius, Borers, casebearers, nets Moths (webworms), Lepidoptera moths 121 201204254 (coneworms), cabbageworms (cabbageworms) and larvae (Pyralidae) in the snail (skeletonizers) (eg: European corn snails (European corn snails) Ostrinia nubilalis Httbner), Amyelois transitella 5 Walker, Cornus caliginosellus Clemens, Grassland Moth (Pyralidae: Grass Filling) Crambinae) is like a grass worm (Herpetogramma licarsisalis Walker), a sugarcane caterpillar (Chilo infuscatellus Snellen), a tomato minor worm (Neoleucinodes elegantalis Guen6e) )), Cnaphalocerusmedinalis, Desmia funeralis Httbner, Melonia (Diaphania niti) Dalis Stoll )), larvae inside the cabbage (Helluala hydralis Guende), yellow snail (Scirpophaga incertulas Walker), early budworm (Scirpophagainfuscatellus Snellen), white name stem Insect (Scirpophagainnotata Walker), bud worm (Scirpophaga nivella Fabricius), dark-headed rice worm (Taiwan rice mold ((^1〇口〇1&gt;^1«75115]\ 46&gt;〇^1〇), Brassica chinensis (Crocidolomia binotalis English); Torricidae's small leaf moth, aphid, seed worm and fruit worm (eg apple leaf curl) Moth (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteana Clemens), oriental fruit moth (Grapholita 25 molesta Busck), citrus pseudo-apple moth (Cryptophlebia leucotreta Meyrick), citrus surname (hanging orange)

S 122 201204254 Ecdytolopha aurantiana Lima ), Argyrotaenia velutinana Walker, Choristoneurarosaceana Harris, apple light brown Leaf moth (Epiphyas postvittana 5 Walker), European berry moth (Eupoecilia ambiguella Httbner), apple bud leaf moth (Pandemis pyrusana Kearfott), small omnivorous Leaf moth (Platynota stultana Walsingham), Pandemis cerasana (Hubner), ίο Pandemis heparana Denis &amp;Schiffermliller); Many other economically important lepidoptera (eg, Plutella xylostella Linnaeus), cotton red bollworm (Pectinophora gossypiella Saunders), gypsy moth (Gypsy moth (Lymantria 15 dispar) Linnaeus)), Carpathina niponensis Walsingham, peach bud moth (Anarsia li Neatella Zeller )), potato moth (Phthorimaea operculella Zeller), spotted leaf pot (Lithocolletis blancardella Fabricius), Asian apple 2〇 Loose leaf rope (Lithocolletis ringoniella

Matsumura)), tumor fill (Lerodea eufala Edwards), apple leaf miner (Leucoptera scitella Zeller); eggs of order Blattodea, nymphs and adults Including 裴蠊 裴蠊 与 蟑螂 ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( ( Blattella germanica Linnaeus), Supella longipalpa Fabricius, Periplaneta americana Linnaeus, brown weft (Periplaneta brunnea) Burmeister)), Leucophaea maderae Fabricius, Periplaneta fuliginosa Service, Australian eagle (Periplaneta australasiae Fabr.) )), lobster Na (Nauphoeta cinerea Olivier) and smooth 蟑螂 (Symploce pallens Stephens)); ίο 朝朝 (orde r Coleoptera) eggs, leaf-feeding, fruit-feeding, root-feeding, seed-feeding and larvae and adulthoods of vesicular tissues, including the elephant trunks of the genus Corydalis, the genus Insects (eg, cotton weevil (Anthonomus grandis Boheman), rice water weevil (Lissorhoptrus oryzophilus i5 Kuschel), valley elephant (Sitophilus granarius Linnaeus) )), rice weevil (Sitophilus oryzae Linnaeus), annual blue weevil (Listronotus maculicollis Dietz), bluegrass elephant (Sphenophorus parvulus Gyllenhal) )), Hunting Elephant (Sphenophorus venatus vestitus), Sphenophorus cicatristriatus Fahraeus; Chrysomelidae's Flea, Cucumber Leaf, Rootworm, Leafhopper , horse-eared potato beetle and leaf miner (eg, Colorado potato beetle potato aphid (Leptinotarsa decemlineata 25 Say), western corn rootworm (corn root leafhopper (Diabrotic) a virgifera virgifera LeConte))); chafer and other chafers (famiiy

S 124 201204254

Scarabaeidae) beetle (eg, Popillia japonica Newman, Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse)

Baraud )), Cyclocephala borealis Arrow, 5 Cyclocephala immaculata Olivier or C. lurida Bland, Aphidius spp., Ataenius spretulus Haldeman ), Cotinis nitida Linnaeus, Maladera castanea Arrow, Phyllophagaspp. and Rhizotrogus majalis Razoumowsky; Carnival aphid of Dermestidae ; Neelidae's nematode; Scolytidae's bark beetles and Tenebrionidae's barkbeetles. In addition, agronomic and non-agronomic pests include: eggs of the order Dermaptera 15 , adult and larvae including the mites of the family Polygonaceae (eg, the mantle (Forficula auricularia Linnaeus), black mites) C (Chelisoches morio Fabricius)); Hemiptera and Homoptera eggs, immature worms, adults and nymphs, such as the blind pile of the Miladae, Zen A genus of the genus Cicadidae, a leaf bud of the genus Cicadelidae (eg, 'Empoasca spp.), a bed bug of the genus Cimicidae (eg, Cimex lectularius Linnaeus) , the genus Fulgoroidae and the genus Deiphaddae, the genus of the genus Membracidae (treeh〇ppers), the psyllids of the genus Psyllidae, the genus (Aleyrodidae) white air (hiteflies), insect dentistry (Aphididae), insects, nodules 125 201204254 Phylloxeridae root nodule, whitefly (.Pseudococcidae) of white 蚧 (meaiybugs), 科科* ( Coccidae ), Shield (Di Aspididae and Margarodidae's scale insects, Tingidae's nettle, 5 Pentatomidae's cultivar, Lygaeidae's long bee (eg, polychaete (long hairy) Blissus leucopterus hirtus Montandon and the South (BUssus insularis)

Barber))) and other seed mites, the genus Cerc〇pidae, the genus of Coreidae, and the red mites and mites of the pyrrh〇c〇ridae . Also included are the eggs, larvae, nymphs and adults of the Acad (Acre), such as the spiders of the Tetranychidae and the red dragonfly (eg European red pheasant (Panonychus ulmi Koch)) , Tetranychus urticae Koch, Tetranychus 15 mcdanieli McGregor; Tequila pygmaea (eg, citrus flat mite) (Brevipalpus lewisi McGregor)); Eriophyidae rust and buds and other leafhoppers and worms important for human and animal health, namely epidermoptidae 2 尘 尘 、 D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D Monument (Ix〇des scapUiaris Say)), Australia to the eclipse monument (ix〇des h〇i〇cyclus Neumann), the American dog monument (Dermacentor variabilis 25 Say), lone star Wall wind (Amblyomma americanum Linnaeus) and Argasidae Ticks, commonly referred to as a soft 126

S 201204254 Monument (for example: relapsing fever tick (Omithodorosturicata), common chicken mites (Argas radiatus); soroptidae, pampas Pyemotidae and Sarcopteridae; Orthoptera eggs, adult and immature worms, including cockroaches, worms, moths, and crickets (eg migratory grasshoppers) (For example, Melanoplus sanguinipes Fabricius, M. differentials Thomas), American cockroaches (for example: Schistocerca americana ίο Drury), desert flying insects (desert wall) (Schistocerca gregaria Forskal )), migratory locust (Locusta migratoria Linnaeus), shrub worm (Zonocerus spp.), ape (Acheta domesticus Linnaeus), cockroach (eg brown 蝼蛄 ( Scapteriscus vicinus Scudder )) and southern 蝼蛄i5 (Scapteriscus borellii Giglio-Tos); eggs of the Diptera (Diptera), adults and immature worms, including the leaf miner (eg Liriomyza spp., such as serpentine vegetable leafminer (Liriomyza sativae Blanchard), earthworm, fruit fly (Tephritidae), yellow 2 scorpion flies (eg: Oscinella frit Linnaeus), soil sisters, homes (eg, Muscadomestica Linnaeus), small home ropes (eg, yellow-bellied flies (Fannia canicularis Linnaeus, stocks) F. femoralis Stein), exhaustion (eg, Stomoxys calcitrans Linnaeus), facial rope, horn rope, black fly (eg, Chrysomya spp., Phormia) Spp.)) and other scorpion pests, horse flies (such as: genus Tabanusspp, bot 127 201204254 flies) (eg: Gastrophilus spp., Oestrus spp. ), cowhide rope (cattle grubs) (eg, Hypoderma spp.), deer flies (eg, Chrysops spp.), sheep snails (eg, sheep wind rope (Melophagus ovinus Linnaeus) And its 5 short-horned suborders (Brachycera), mosquitoes (eg Aedes sp.) P_ ), Anopheles spp., Culex spp., Prosimulium spp_, Simulium spp., cockroach, sand fly, cockroach and other long Nematocera; eggs, adult and immature individuals of order Thysanoptera include ίο onion thrip horse (Thrips tabaci Lindeman), flower thrip horse (Frankliniellaspp.) ) and other leaf-feeding thrips; the order Hymenoptera insect pests, including ants in the ant family, contain Florida wood ants (Camponotus floridanus Buckley), redwood sacrifice (red bow ant is is ( Camponotus ferrugineus Fabricius )), black carp (Camponotus pennsylvanicus De Geer), white foot moth (Technomyrmex albipes fr. Smith), big ant (Pheidole sp .)), pin 蠛 (Tapinoma melanocephalum Fabricius); Pharaoh ant (Monomorium pharaonis Linnaeus), small fire ant (Wasmanniaauropunctata Roger), Sacrifice (Solenopsis geminata Fabricius), Insecurious Red Fire Ant (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), mad ant (Paratrechina 25 longicornis Latreille), paving ant (road ant (Tetramorium caespitum Linnaeus)), corn field ants (Lasius s 128 201204254 alienus FOrster) and odorant ants (Tapinoma sessile Say). Other Hymenoptera include honeybees (including wood bees), bumblebees, wasps, wasps, and miners (Neodiprion spp.; Cephusspp.); Order Isoptera insect pests include white mites in the termite family (eg, Macrotermes spp., Odontotermes obesus Rambur), and woody genus (eg, Cryptotermes spp. )) and the termite termites (for example: Reticulitermes spp. 'Coptotermes spp.', 'Heterotermes tenuis Hagen'), and oriental subterranean termites (Reticulitermes flavipes) Kollar)), Western subterranean termites (Reticulitermes hesperus Banks), Taiwan's underground termites (Coptotermes formosanus Shiraki), West Indian dry wood termites (Indigenous white scorpion is (Indigenous white scorpion is (Casisitermes immigrans Snyder) ), termites (Cryptotermes brevis Walker), dry wood termites (Incisitermes snyderi Light), southeast subterranean termites (South) Reticulitermes virginicus Banks), Western stem wood termites (Incisitermes minor Hagen), tree termites, 2 such as the termite genus (Nasutitermes sp.) and other economically important termites; Order Thysanura) insect pests such as squid (Lepisma saccharina Linnaeus) and house fish (Thermobia domestica Packard); orderMallophaga insect pests, including head lice (human Pediculus humanus capitis De Geer), physiology (Pediculus humanus Linnaeus), chicken body benefit (大鸡益129 201204254 (Menacanthus stramineus Nitszch)), dog dish (Canine 响毛盘(Trichodectes) Canis De Geer)), fluffy plate (Goniocotes gallinae De Geer), sheep body (Bovicola ovis Schrank), short-nose calf (Haematopinus eurysternus Nitzsch) ), long-nosed cattle are (Linognathusvituli Linnaeus) and other attacks on humans and animals, stimulating and vomiting; erSiphonoptera) insect insects contain tropical rat eggs (Xenopsylla cheopis Rothschild), cat mites (Ctenocephalides 10 felis Bouche), dog mites (Ctenocephalides canis Curtis), poultry C (Ceratophyllus gallinae Schrank), chi E (Echidnophaga gallinacea Westwood), 蚤 P (Pulexirritans Linnaeus) and other mites that afflict mammals and birds; covered Other section 15 Limb pests include: Araneae's Φ spiders, such as: Loxosceles reclusa Gertsch &amp; Mulaik, and the black widow spider (Latrodectus mactans Fabricius), and The entertainment of the order Scutigeromorpha, such as Scutigera coleoptrata Linnaeus ° 2 The compound of the present invention shows a particularly high activity against pests of the order Lepidoptera (eg: cotton leaf worm (Alabama) Argillacea Httbner (cotton leaf worm)), fruit tree yellow moth (Archips argyrospila Walker (fruit tree leaf moth) Af roller))), rose leaf moth (A. (European leaf curler) and other species of Archips (Archips) 25 species, Chilo suppressalis Walker (rice worm), wild filling ( Cnaphalocrosis medinalis Guen6e) (rice leaf 201204254 insect), Crambus caliginosellus Clemens (corn root moth), Crambus teterrellus Zincken (bluegrass moth), apple moth (Cydia pomonella) Linnaeus), Earias insulana Boisduval (King Kong 5 diamonds), Erias vittella Fabricius (Hymenoptera), Helicoverpa armigera Hiibner (H. ), Helicoverpa zea Boddie (H. armigera), Heliothis virescens Fabricius (tobacco budworm), Herpetogramma licarsisalis Walker (grass ίο), grape leaflet Moth (Lobesia botrana Denis &amp;

Schiffermttller (P. berry), cotton red bollworm (Pectinophora gossypiella Saunders), Phyllocnistiscitrella Stainton, and Pieris brassicae Linnaeus (Pieris brassicae Linnaeus) , Cabbage 15 butterfly (Pieris rapae Linnaeus), Plutella xylostella Linnaeus, Spodoptera exigua Hubner, Spodoptera litura Fabricius (Tobacco night worm, two-pointed false-winged moth), Spodoptera frugiperda J. E. Smith (Tropical night 2 moth), Trichoplusia ni Hiibner (prototype) Tuta absoluta Meyrick (painted and photographed worm) 〇 The compound of the present invention also has significant activity against members of the Homoptera, including: Acyrthosiphon pisum Harris (婉豆蚜), Black Beans (Aphis craccivora Koch) 25 (Red Beans 1 worm), Black Beans (Aphis fabae Scopoli) (Black Beans), Cotton (Aphis gossypii Glover), 131 201204254 Aphis pomi De Geer (Apple locust), Aphis spiraecola Patch (Aphis spiraecola Patch), Acacorthum solani Kaltenbach (Suu worm), Chaetosiphon fragaefolii Cockerell (grass per worm: worm), 5 Russian wheat double-tailed pheasant (Diuraphis n〇xia KurdjumoWMordvilko) (Russian wheat glutinous rice), the front of the car, Dysaphis plantaginea Paaserini), Eriosoma lanigerum Hausmann (Apple, Miancai), Hyalopterus pruni Geoffroy (Peach Pink), Pseudo 10 (Lipaphis erysimi Kaltenbach) (Mustard Series), Metopolophium dirrhodum Walker (Valley)

Macrosiphum euphorbiae Thomas (other S long tube), Myzus persicae Sulzer (Peach, peach), Nasonovia ribisnigri Mosley (Lettuce), 15 痩Aphis ( Pemphigus spp.), Rhopalosiphum maidis Fitch (corn leaf pair), Rhopalosiphum padi Linnaeus (黍溢财), Schizaphis graminum Rondani (Green worm), Sitobion avenae Fabricius (Guicai), g Therioaphis maculata Buckton (苜蓿 财 财), 小 财 财 (Toxoptera aurantii Boyer de Fonscolombe) (Black Tang Cai ) and Toxoptera citricida Kirkaldy (brown tangerine); Adelges spp.; Phylloxera devastatrix Pergande (Peas fuliginea 25); Tobacco whitefly ( Bemisia tabaci Gennadius (smoke powder, sweet potato powder wind), silver leaf whitefly (Bemisia argentifolii Bellows &amp; s 132 201204254

Perring (Silver Leaf Powder), Dialeurodes citri Ashmead and Trialeurodes vaporariorum Westwood; Potato Leafhopper (Empoasca fabae Harris) ), Laodelphax striatellus Fallen, Macrollestes quadrilineatus Forbes, Nephotettix cinticeps Uhler, Black-tailed spider mites (Nephotettix nigropictus St (Indica), brown rice glutinous rice (Nilaparvata lugens StM), corn pterygium γ (Peregrinus maidis Ashmead), white back fly (Sogatella furcifera Horvath) (White-backed wind)), American rice-flying insect (Sogatodes orizicola Muir), apple white-leaf (Typhlocyba pomaria McAtee), and Erythroneoura spp. ); 17 years of 蝉is (Magicidada septendecim Linnaeus (cycle)); blowing insects (IceryapurchasiMaskell) Dra 盾 盾 ( (Quadraspidiotus perniciosus Comstock.); ococcus 橘 橘 (Planococcus citri Risso (orange powder)); Membrane (Pseudococcus spp. (Other Fanling Complex)); Cacopsylla pyricola Foerster and Trioza diospyri Ashmead. The compounds of the invention are also active against members of the Hemiptera, including: Acrosternum hilare Say, Anasatristis De Geer, and Blissus 25 leucopterus. Leucopterus Say (long carp), temperate bed bug (cimex lectularius Linnaeus (bed)), cotton net culture (Corythuca gossypii 133 201204254

Fabricius (cotton net)), Cyrtopeltis modesta Distant, Dysdercus suturellus Herrich-Schaffer, Euchistus servus Say ), a stagnation (Euchistus variolarius Palisot 5 de Beauvois), Groptosthetus spp_ (species 蝽 complex), pine rim (Leptoglossus corculus Say), Lygus lineolaris Palisot De Beauvois (herbivore), rice green (Nezara viridula Linnaeus), rice (Oebalus pugnax Fabricius), Oncopeltus fasciatus Dallas Milkweed bee) and cotton blind mites (Pseudatomoscelis seriatus Reuter). Other insects controlled by the compounds of the present invention include Thysanoptera (eg, Frankliniella occidentals Pergande ( Western flower thrips)), Citrus thrips is (Scirthothrips citri Moulton), Soybean rips (Sericothrips var) Iabilis Beach (), and Thrips tabaci Lindeman (onion thrips); and coleoptera (orcjer Coleoptera) (eg, Leptinotarsa decemlineata Say (Colorado potato), Mexican beans Ladybug 2 (Epilachna varivestis Mulsant) and Mexican genus, the iron worm, the Athous genus or the genus Limonius. Note that some contemporary classification systems will be Homoptera. (Homoptera) is classified as a suborder under Hemiptera. 25 Notable is the use of the compound of the present invention for controlling silver leaf whitefly (Bemisia argentifolii).

S 134 201204254 The use of a compound of the invention for the control of western flower thrips (Frankliniella occidentals). It is worth noting that the compounds of the present invention are useful for controlling the use of Myzus persicae. Of note, the use of the compounds of the invention for the control of the diamondback moth (Plutella xylostella). It is worth noting that the compounds of the present invention are useful for controlling autumn army worms (Spodoptera frugiperda). The compounds of the invention may also be inhibited with one or more other biologically active compounds or including fungicides, insecticides, nematicides, bactericides, acaricides, herbicides, herbicide antidote, such as insect molting Agents and rooting stimulants of growth regulators, chemical sterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, plant nutrients Agents, other biologically active compounds or a mixture of entomopathogenic bacteria, viruses or fungi to form a multi-component pesticide' provide a wider range of agricultural protection. The invention therefore also relates to a composition comprising a biologically effective amount of a compound of formula 1, at least one additional component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, and at least one additional biological activity. a compound or agent. With regard to the mixtures of the invention, other biologically active compounds or agents may be formulated with the compound of Formula 1 to form a premix or one or more other biologically active compounds or agents with Formula 1 The compounds of the invention are formulated separately and the formulations are combined together (e.g., in a spray tank) prior to administration, or successively. The bioactive compound or agent which can be formulated with the compound of the present invention is an insecticide such as abamectin, dinosaur 135 201204254 (acephate), sub-volume (aceqUin0Cyi), acetamiprid. , acet〇pr〇ie, acrinathrin, azudfjumet, amitraz, avermectjn, azadirachtin , azjnph〇s_methyl, bifenthdn, bifenazate, bistrifluron, borate, bupr〇fezin, cadusafos , carbaryi, carb〇furan, cartap, carz〇1, chl〇rantraniHpr〇le, chifany ), chlorfluazuron, chi〇rpyrifos, chlorpyrifos-methyl, chr〇mafenozide, clofentezin, ci〇thianidin, Cyanotrapro (3·bromo-1-(3-Ga-2-pyridyl)_Ν· [4. Cyano-2- 15 methyl [(decyl)) phenyl]-lH-n than sal-5-nonylamine), cyflumetofen, cyfluthrin , beta-cyfluthrin, cyhal〇thrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha Alpha (alpha-cypermethrin), 2〇ζze-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, and diltiag ( Dieldrin ), diflubenzuron, dimefluthrin, dimehypo, dimethoate, dinotefuran, diofenolan, Emmectin, endosulfan, Yihuali

S 136 201204254 (esfenvalerate ), ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb, fenoxycarb, Fenpropathin, fenvalerate, fipronil, flonicamid, flubendiamide, flUCythrinate, flufenerim, fluoride Flufenoxur〇n, fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, six Hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufen Lufenuron, malathion, mepyrfluthrin, metaflumizone, metadehyde, methamidophos, methidathion, annihilation (methiodicarb), meth〇myl, metheprene, methoxychlor, methoxyfenozide, metofluthrin, milbemycin oxime, sub Monocrotophos, nicotine, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, balason (parathion), parathi〇n-methyl, permethrin, ph〇rate, phosalone, 137 201204254 phosmet, blessing Phomamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pymetrozine, Pefolo 5 (pyrafluprole), pyrethrin (pyrethrin), pyridaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, vine Ronetone (rotenone), fish nitin (ry Anodine ), spinetoram, spinosad, 10 spiridiclofen, spiromesifen, spirotetramat, sulfoxaflor, propylene Sulfur-filled (sulprofos), tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, Tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad ), tramamethrin, triazamate, trichlorfon, triflumuron, Bacillus thuringiensis delta endotoxin, entomopathogenic bacteria, entomopathogenic virus And entomopathogenic fungi. It is worth noting that the aforementioned list includes acetoprole, mepyrfluthrin, sulfoxaflor and tetramethylfluthrin. 25 Notable are insecticides for use in combination with the compounds of the invention such as abamectin, acetamiprid, A.

S 138 201204254 纳rina (acrinathrin), amitraz, avermectin, azadirachtin, bifenthrin, buprofezin, cadusafos, plus Carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin , beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, a cyanomethine Alpha-cypermethrin ), zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, Emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenothiocarb, fen Knock fen0XyCarb ), fenvalerate, fipronii, flnnicamid, flubendiamide, flufenoxuron, fluvalinate, formetanate ), fosthiazate, hexaflumuron, hydramethylnon, imidac丨oprid, indoxacarb, iufenuron, mepyrfluthrin ), metaflumizone, methiodicarb, meth〇myl, metoprene, meth〇xyfenozide, enebitilamine 139 201204254 (nitenpyram ) , nithiazine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl ) 'pyripr0Xyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirochete B Spirotetramat, flonicamidonitrile (s Uifoxaflor), tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, insecticide Monosultap-sodium, tralmethrin, triazamate, triflumuron, Bacillus thuringiensis δ endotoxin, all strains of Bacillus thuringiensis and A group consisting of all strains of Nucleo polyhydrosis is viruses. It is worth noting that the aforementioned list of mepyrfliithrin, suifoxaflor and tetramethylfluthrin is not included. Specific examples of biological agents for mixing with the compounds of the present invention include entomopathogenic bacteria such as Bacillus thuringiensis, 2〇 and encapsulated Bacillus thuringiensis delta endotoxin (e.g. 'Cellcap, MPV , MPVII); entomopathogenic fungi, such as green muscardine fungus; and entomopathogenic viruses (including naturally occurring and genetically modified), including baculovirus, nuclear polyhedrosis virus 25 (nucleopolyhedro Virus (NPV), such as: Helicoverpa zea nucleopolyhedrovirus 201204254 (HzNPV), Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV), such as apple Cydia pomonella granulosis virus (CpGV) ° 5 It is worth noting that the other invertebrate pest control active ingredients in the above combination belong to different chemical classes or have different action sites. In some instances, with at least one other invertebrate pest Combinations of control active ingredients which have similar ranges of control but which have different levels of action will be particularly useful for resistance treatment. 10 Thus, the compositions of the present invention may further comprise at least one biologically effective amount of other invertebrate pests. Control the active ingredients, which have similar control ranges but belong to different chemical classes or have different action sites. These other biologically active compounds or reagents include but are not limited to: bifenthrin, Cypermethrin, Xeronine 15 ( Cyhalothrin), ianibda-cyhalothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dimefluthrin, Esfenvalerate, fenvalerate, indoxacarb, mepyrfluthrin, metofluthrin, profluthrin, pyrethrin ), tetramethylfluthrin (tralomethrin); cholinesterase inhibitors, such as chlorpyrifos, nanet (me) Thomyl), oxamyl, thiodicarb, and triazamate; neonicotinoids, such as acetamiprid, clothianidin, Dart Dinotefuran, ideda 201204254 (imidacloprid), nitenpyram, nithiazine, thiacloprid and thiamethoxam; insecticidal giant ring vinegar (macrocyclic lactones)' such as spinetaram, spinosad, 5 abamectin, averniectin and genus, emmectin; GABA (γ- Aminobutyric acid) - a modulator of chloride channel antagonists such as avermectin or blockers such as ethiprole and fipronil; chitin synthesis inhibitors such as buffin Buprofezin, cyr〇mazine, flufenadol, hexaflumuron, lufenur〇n, novaluron, noivifuron and three Triflumuron; youth hormone analogues such as difenolan, fenofol (fen〇xycarb), metopor and pyriproxyfeil; octopamine 15 ( 〇ct〇pamine ) receptor ligands, such as amitraz; quercetin and ecdysone Agents such as azadirachtin 'methoxyfenozide and tebufenozide; ryan〇dine receptor ligands such as ryanodine and ortho-aniline Anthranilic 2〇diamides ' chlorantraniliprole, and cyantraniliprole and flubendiamide; nereistoxin analogs, such as cartap; Mitochondrial electron transport inhibitors, such as chlorfenapyr, hydramethylnon, and pyridaben; lipid-binding inhibitors such as spirodiclofen and snail Spiromesifen); cyclodextene insecticide (cycl〇diene 142 201204254 insecticides), such as dieldrin or endosulfan; pyrethrum; carbamate; glandular killing Fungal agent (insecticidal ureas); And biological agents include nuclear polyhedrosis virus (NPV), 5 members of Bacillus thuringiensis, encapsulated Bacillus thuringiensis delta endotoxin, and other naturally occurring or genetically modified insecticidal viruses. Further examples of bioactive compounds or agents which may be formulated with the compounds of the invention are: fungicides, such as acibenzolar (i.e., arsenic acid benzene-S-methyl ίο (already; (by 61^〇131&gt;;-8-11^1^1)), 4-dodecyl-2,6-dimethyl-allinate (aldimorph), octanoic acid (ametoctradin), 〇引0素素素Amisulbrom ), anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxyl-M), wheat rust 15 Benodanil, benomyl, benthiavalicarb, benthiavalicarb-isopropyl, bethoxazin, binapacryl, binomial , biphenyl, bitertanol, bixafen, blasticidin_S, Bordeaux mixture (tribasic copper sulfate), acetamiprid (white) Boscalid / nicobifen), bromuconazole, bupirimate, 得灭多 (bu Thiobate ), carboxin, carpropamid, captafol, captan, carbendazim, chinomethionat, dimodan Chloronib), tetra-isophthalonitrile 143 201204254 (chlorothalonil), chlozoHnate, clotrimazole, copper oxide (XyChl〇ride), copper salts (eg copper sulfate and copper hydroxide) , cyazofamid, cyflufenamid, cyin〇xanil, cyproconazole, Cypr〇dinil, dichlofluanid, dicyanidin Diclocymet, diclomezine, dicloran, diethofencarb, diethofencarb, diflumetorim, dimethirimol, Dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinocap, discostrobin, dithianon ), twelve rings of dodemorph Dodine, econazole, enestroburin, etaconazole, edifenphos, epoxiconazole, ethaboxam, Ethirimol, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, guanfuwei 2 Fencaramid, fenfuram, fenhexamide, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, three Fentin acetate, fentin hydroxide, dimethylamine thiocarbamate (ferbam), 25 ferfurazoate, ferimzone, giazinam ), 0 fludioxonil, flubenzamide

S 144 201204254 (flumetover ), flumorph, fluopicolide, fluorine, fluopyram, fluoroimide, fluoxastrobin, flurazepam (fluquinconazole), flusilazole, flusulfamide, flutolanil, flutriafol, fluxapyroxad, folfet, forsythia (fosetyl-aluminum), fuberidazole, furalaxyl, furametapyr, hexaconazole, hymexazol, hymexazol, gram fever Guazatine, imazalil, imibenconazole, iminoctadino, iodicarb, ipoconazole, iprobenfos, yiputong Iprodione), iprovalicarb, isoconazole, isoprothiolane, isopyrazam, isotianil, kasugamycin Ke Kexin (kresoxim-me Thyl), mancozeb, mandipropamid, maneb, mapanipyrin, mefenoxam, mepronil, Oxyacetic acid-based white powder (meptyldinocap), metalaxyl (including mettalol-M), metconazole, methasulfocarb, metiram, methamphetamine (metominostrobin) /fenominostrobin ), 0 mepanipyrim, metrafenone, miconazole, myclobutanil, new azuren 145 201204254 (neo-asozin) ( ferric methanearsonate ( Whetstone Shenshen)), nuarimol, octhilinone, ofurace, oressastrobin, oxadixyl, oxolin Oxolinic acid, oxpoconazole, oxycarboxin, paclobutrazol, penconazole, pencycuron, penflufen , 0 to pceporin (penthiopyrad), rice Perfurazoate, phosphonic acid (ie, sub-acid and its salts), phthalide, picobenzamid, picoxystrobin, piperalin , p〇ly〇xin, probenazole, prochloraz, procymidone, pr〇pamocarb, propamocarb-hydrochloride ), propiconazole, pr〇pineb, proquinazid, pr〇thiocarb, prothioconazole, pyracino Str〇bin), pyramitostrobin, pyraoXyStr〇bin, pyrazophos, pyribencarb, Pyributicarb, bifenfen ( Pyrifenox ), pyrimethanil, pyrifenox, pyriofenone, pyrrolnitrin, pyroquilon, quinck (qUjnconaz〇ie), venofen (quinoxyfen), five-gas benzene (quint〇zene), match First 25 (sedaxane), silicon penthiopyrad (silthiofam), silicon-fluoro-oxazole (simeconazole), mulberry cyclosporine (Spiroxamine), streptomycin

S 146 201204254 (streptomycin), sulfur (sulfur), tebuconazole, tebufloquin, teci〇ftaiam, tecnazene, tetraconaz〇ie ), thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tia (jinil), detached Tolclofos-methyl, toiyifluanid, triadimefon, triadimenol, triarimol, imidazole [triaz0Xide], thirteen? Tridemorph, triflumizole, trimorphamide, tricyciaz〇ie, trifloxystrobin, triforine, triticonazole, Uniconazole, validamycin, and validamycin, vinclozolin, Zineb, Ziram, and zoxamide; Nematicides, like aidicarb, Nicotine (imicyafos), oxamyl and fenamiphos; fungicides, such as streptomycin; acaricides such as amitraz, chinomethionat, gram Benzene (chlorobenzilate), cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpenin (fenpropathrin), fenpyroximate, hexythiazox, propargite, pyridaben, and tebufenpyrad. It is worth noting that it does not include carbendazim ( Anilazine ), benodanil, bei xinxin 147 201204254 (bethoxazin), binapacryl, bixafen, chinomethionat, diflumetorim, dipyrimidine Dimethirimol, enestroburin, flumorph, fluopyram, fluoroimide, fluxapyroxad, isopyrazam ), Isotianil (isotrianil) , oxyacetate-based white powder (meptyldinocap), powderalin (piperalin), prothiocarb, pyributicarb, pyrofenone, sedaxane, and safari ίο ( The aforementioned list of triflumizole). In certain instances, the compounds of the invention and other biologically active (particularly invertebrate pest control) compounds or agents (i.e., active ingredients) may result in an effect of one plus one greater than two (i.e., synergistic). Therefore, the environmental discharge of the active ingredient can be reduced, and at the same time, the effective control effect can be ensured. When the invertebrate pest control active ingredient exhibits a synergistic effect on the agronomically sufficient level of invertebrate pest control, the combination can be beneficial for reducing crop production costs and reducing environmental burden. The compounds of the present invention and compositions thereof are applicable to genetically transformed plants to express toxic proteins to invertebrate pests (e.g., BaciUus thuringiensis δ-endotoxin). This application provides a wider range of plant protection as well as resistance to drug resistance management. The effect of the invertebrate pest control compound of the present invention applied externally may synergize with the toxic protein of the expression. General references for these agricultural protective agents (ie insecticides, fungicides, nematicides, acaricides, herbicides and biological agents)

References include The Pesticide Manual, 13th Edition, C. D 201204254 S. Tomlin, Ed., British Crop Protection Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Manual, 2nd Edition, L. G. Copping, Ed., British Crop Protection

Council, Famham, Surrey, U.K., 2001. 5 In embodiments in which one or more of these various different mixing moieties are used, the weight percentage of these various mixed moieties (all) to the compound of Formula 1 is typically between about 1:3 Torr and about 3000:1. . It is noted that the weight percentage is between about 1:300 and about 300:1 (e.g., a percentage between about 1:30 and about 30:1). This artist can easily determine the biologically effective amount necessary for the active ingredient to achieve the desired biological activity range through simple experiments. It is evident that the inclusion of these additional ingredients extends the range of invertebrate pest control beyond the scope of the single use of the compound of formula 1. Table A lists the combination of the compound of Formula 1 with other invertebrate pest control agents 15 which illustrate the mixtures, compositions and methods of the present invention. Table A first lists the specific invertebrate pest control agent (for example, "abamectin" in the first row). The mode of action (if known) or chemical species of the 5 hai invertebrate pest control agent is listed in the second column of Table A. An example of the weight ratio range of the invertebrate pest control agent phase 20 to the compound of formula 1 is listed in the third column of Table A (for example, the weight ratio of abamectin to the compound of formula X is "5" :1 to 1:50"). Thus, for example, the first row of Table A specifically discloses a composition of a humanoid composition with abamectin using: a weight percentage between 50:1 and 1:5. The structure 25 of the remaining rows of Table D1 is similar to the 'step-by-step note for the list of specific compounds of formula i in combination with other invertebrate pest control classes, which illustrate the 149 201204254 mixture, composition and method of the present invention, and Examples of ranges of weight ratios including other application rates are included.

Table A

S Invertebrate pest control agent mode of action or chemical classification usually weight ratio of abatatin giant lactone ring 50:1 to 1:50 sub-exeter neonicotinoid 150:1 to 1:200 double-mercapto fibrin Body ligands 200:1 to 1:100 Abamectin macro lactone ring 50:1 to 1:50 Azadirachtin ecdysone agonist 100:1 to 1:120 Beta-Secuna sodium channel regulation Agent 150:1 to 1:200 Phenfenin sodium channel modulator 100:1 to 1:10 Buphin net chitin synthesis inhibitor 500:1 to 1:50 Pedanic silkworm toxin analogue 100:1 to 1:200克安布内丁丁Receptor ligand 100:1 to 1:120 克凡派 mitochondrial electron transport inhibitor 300:1 to 1:200 Tausson cholinesterase inhibitor 500:1 to 1:200 Cotinine Nicotinic 100:1 to 1:400 gas cyrantraniliprole Fish nitin receptor ligand 100:1 to 1:120 Saifuning sodium channel modulator 150:1 to 1:200 Cylonine channel regulation Agent 150:1 to 1:200 Safranine Channel Modulator 150:1 to 1:200 Saline Synthetic Inhibitor 400:1 to 1:50 Sodium Channel Suppressor 50:1 to 1 :400 ground Ringer diene insecticides 200:1 to 1:100 Datnam neonicotinoids 150:1 to 1:200 Benzolid ether peeling inhibitor 150:1 to 1:200 chlorfenapyr macrolides 50:1 to 1:10 killing cyclopentene insecticides 200:1 to 1:100 Yihuali sodium channel regulator 100:1 to 1:400 Ethylamine GABA-regulated chloride channel blocker 200 :1 to 1:100 thiol 150:1 to 1:200 Fenokee youth hormone analogue 500:1 to 1:100 Fenicide sodium channel modulator 150:1 to 1:200 Fenpney GABA regulating gas Ion channel blocker 150:1 to 1:100 fluniamine 200:1 to 1:100 flufenamide nicotine receptor ligand 100:1 to 1:120 flufenazone chitin synthesis inhibitor 200 :1 to 1:100 hexamone chitin synthesis inhibitor 300:1 to 1:50 150 201204254 Invertebrate pest control agent action mode or chemical classification usually weight ratio Amesson mitochondrial electron transport inhibitor 150:1 to 1 :250 EDTA neonicotinoids 1000:1 to 1:1000 Indacyl channel modulators 200:1 to 1:50 λ Xeronine channel modulators 50:1 to 1:250 Lufenlong Qualitative Inhibitor 500:1 to 1:250 mepyrfluthrin sodium channel modulator 100:1 to 1:400 US fluoride 200:1 to 1:200 nanodine cholinesterase inhibitor 500:1 to 1 :100 Maximal Youth Hormone Analog 500:1 to 1:100 Defenofin Ecdysone agonist 50:1 to 1:50 Nitenpyram neonicotinoid 150:1 to 1:200 Nitroacetamide Neonicotinoids 150:1 to 1:200 Novalon chitin synthesis inhibitor 500:1 to 1:150 殴kill cholinesterase inhibitor 200:1 to 1:200 Defeated 200:1 to 1:100 Pyrethrin Sodium Channel Modulator 100:1 to 1:10 Pythaben mitochondrial electron transport inhibitor 200:1 to 1:100 ϋ定虫丙鳞200:1 to 1:100 Bollipane youth Hormone Analogs 500:1 to 1:100 Fish Nitinus Nitin Receptor Ligand 100:1 to 1:120 Cinotex Macrolide Rings 150:1 to 1:100 500:1 to 1:10 Schiffin lipid biosynthesis inhibitor 200:1 to 1:200 Oxime ester lipid biosynthesis inhibitor 200:1 to 1:200 Sulfoxaflor 200:1 to 1:200 Defenofin ecdysone agonist 500:1 1:250 Tetramethylfluthrin sodium channel regulator 100:1 to 1:40 Sai Pei neonicotinoid 100:1 to 1:200 Sai Su Anxin in the test class 1250:1 to 1:1000 Sulfuric acid cholinesterase inhibitor 500:1 to 1:400 insecticidal double 150:1 to 1:100 tetramethrin sodium channel modulator 150:1 to 1:200 oxazolidine cholinesterase inhibitor 250:1 to 1:100 Sanford Chitin Synthetic Inhibitor 200:1 to 1:100 Suzyme Biological Agent 50:1 to 1:10 Bacillus thuringiensis δ endotoxin biologic 50:1 to 1:10 Nuclear polyhedrosis virus (eg, Gemstar) biological agent 50:1 to 1:10 151 201204254 It is noted that the compounds of the invention comprise at least one other biologically active compound or agent which is selected from the list listed in Table A. Vertebrate pest control agent. The weight ratio of the compound (including the compound of formula 1, its N-oxide or its salt) to other invertebrate pest control agents is usually between 1000:1 and 1:1000, and one embodiment is between 500:1. Between 1:500, another embodiment is between 250:1 and 1:200, and another embodiment is between 100:1 and 1:5〇. The following Tables B1 to B45 are examples of specific compositions comprising the compound of Formula 1 (Compound No. (Cmpd. No.) Reference Index Tables a to F) and other invertebrate pest control agents. Table B1 Mixture Number Compound Number and invertebrate pest control mixture number compound number and invertebrate pest control agent A-1 1 and Abatin A-37 1 as well as Indek A-2 1 and Amphibious A-38 1 and Ram达##洛宁A-3 1 and amitraz A-39 1 as well as rifampin A-4 1 and avermectin A-40 1 as well as mepyrfluthrin A-5 1 and indosin A -41 1 and US Gas A-6 1 and Beta Savoning A-42 1 and Na Nai A-7 1 and Bifennin A-43 1 and Meiseiping A-8 1 and Bufenjing A-44 1 and fentanyl A-9 1 as well as Pedan A-45 1 and nitenpyram A-10 1 as well as gram A-46 1 and nitrile thiazole A-11 1 and kefanai A-47 1 And Norvaron A-12 1 and Dossson A-48 1 as well as cockroach A-13 1 and konidine A-49 1派灭净 A-14 1 and cyantraniliprole A-50 1 and pyrethrin A-15 1 as well as Sai Fanning 51 51 1 and Pythamoto A-16 1 and Xeron Α · 52 1 and bite C-A-17 1 and Sai-Ning-53 1 and Balippfen

152 S 201204254 Mixture number compound number and invertebrate pest control agent A-18 1 and cyanobacteria A-19 1 and 灭宁Α·20 1 and Descendants Α-21 1 and Datnam Α-22 1 And P. sinensis -23 1 and Pseudomonas Α-24 1 and amphibious Pan Α-25 1 and Yihua Li Α -26 1 and B. sinensis -27 1 and fenthion -28 1 and fen Knock -29 1 and Fennel Α-30 1 as well as Fenpini Α-31 1 and flunislide 32-32 1 and flufenamide 33-33 1 and flufenonone 34 1 and 6 volts隆Α-35 1 and Amy Pine-36 1 and edaramine mixture compound and invertebrate pest control number number Α-54 1 and 尼尼丁Α-55 1 and 诺诺Α-56 1 and Killing -57 1 and giving points -58 1 and formazan Α-59 1 and sulfoxaflor Α-60 1 as well as fenfenone-61 1 and Tetramethylfluthrin Α -62 1 and Sai Pei-Α -63 1 and Sai An An-64 1 and Sulfur -65 1 and insecticidal biguanide-66 1 and tetramethrin Α-67 1 as well as 嗤蚜威Α-68 1 and Sanfulong Α-69 1 and Su bacterium Α-70 1 and Bacillus thuringiensis δ Toxin 71-71 1 and nuclear polyhedrosis virus (eg, Gemstar) Tables B2 to B45 are each similar to the construction of Table B1 above, except that the items listed under the heading "Compound Number" are listed below. Replace. Therefore, for example, in Table B2, the items under the column heading "Compound Number" are listed as "Compound 2", and the first line under the column heading in Table B2 specifically discloses a mixture of Compound 2 and abamectin. . Tables B3 to B45 have similar structures. Form number Compound number rotten item Form number B2 Compound 2 ~ B24 B3 Compound 3 B25 B4 Compound 5 B26 Compound number column Item Compound 112 Compound 114 Compound 119 153 201204254 Grid number Compound number block item table number Compound number block item B5 Compound 16 B27 compound 120 B6 Compound 17 B28 Compound 121 B7 Compound 25 B29 Compound 122 B8 Compound 29 B30 Compound 123 B9 Compound 35 B31 Compound 127 B10 Compound 52 B32 Compound 130 B11 Compound 58 B33 Compound 131 B12 Compound 59 B34 Compound 147 B13 Compound 60 B35 Compound 150 B14 Compound 66 B36 Compound 152 B15 Compound 68 B37 Compound 153 B16 Compound 69 B38 Compound 155 B17 Compound 71 B39 Compound 158 B18 Compound 72 B40 Compound 163 B19 Compound 80 B41 Compound 168 B20 Compound 85 B42 Compound 170 B21 Compound 91 B43 Compound 179 B22 Compound 94 B44 Compound 181 B23 Compound 103 B45 Compound 183 is listed as a specific mixture in Tables B1 to B45, which typically combines the compound of Formula 1 with Other invertebrate pest agents, the specific ratios of which are listed in Table A. 5 In agronomic and non-agronomic applications, by applying one or more biologically effective amounts of a compound of the invention (usually in the form of a composition) to a pest environment (including agronomic and/or non-agronomically infested areas), areas to be protected Or directly applied to the pests to be controlled to control invertebrate pests. Accordingly, the invention encompasses a method of controlling 10 invertebrate pests in agronomic and/or non-agronomic applications comprising subjecting the invertebrate pest or its environment to a biologically effective amount of one or more compounds of the invention

S 154 201204254 is contacted or contacted with a composition comprising at least one such compound, or a composition comprising at least one such compound and a biologically effective amount of at least one other biologically active compound or agent. Notably, the plant line in the 'invertebrate pest environment' of the foregoing method is contacted with a biologically effective amount of the compound of the invention (e.g., in the form of a composition of the invention). Examples of suitable compositions comprising a compound of the invention and a biologically effective amount of at least one other biologically active compound or agent include a particulate composition wherein the other active compound is present on the same particles as the compound of the invention, or is present independently of the invention The compound is present on 10 particles of each of them. In order to achieve contact with a compound or composition of the invention to protect crops from invertebrate pests, the compound or composition is typically applied to plant seeds prior to planting, to foliage branches of crop plants (eg, leaves, flowers, fruits) ) or soil before or after crop planting or its 15 growth medium. An embodiment of a method of contacting is by spraying. Further, a granule composition comprising the compound of the present invention can be used for the leaves or soil of plants. By contacting the plant with a soil watering agent, a granule formulation, a soil formulation, a seedling treatment or a soaking solution of the graft, the composition of the present invention is used, and the compound of the present invention can be effectively absorbed by the plant. Transfer. It is worthwhile to think that the composition of the present invention is in the form of a soil reagent liquid formulation. Also of note is a method of controlling an invertebrate pest comprising contacting an invertebrate pest or an environment thereof with a biologically effective amount of a compound of the invention, or a composition comprising a biologically effective amount of a compound of the invention 25 contact. It is further noted that the environment in this method is soil, and the composition is used as a soil reagent for soiling. 155 201204254 The above-mentioned step value is noted in which the compound of the present invention 3 = makes the two T effect. Other methods of contact include aerosol, powders, and many other touches. 1 : Examples are compounds or compositions comprising the present invention. Two fertilizer granules, rods or _. The compounds of the present invention may also be used in the following:: = Implanted invertebrate control device (e.g., insect net) / invertebrate ^ ^ HiΓ can be used for seed treatment to protect seed free content. The present invention discloses and claims the invention. The present invention is formulated into a composition of the invention by contacting the seed with a biologically effective dose of ==. This seed...4 seed protects the seed from 15 20 25 2 3 pairs of seedlings developed from germinating seeds in contact with the soil, 3 through the development of plant seeds or from the state of the invention - a species of protection A method for the protection of plants from human insults by invertebrate pests. Seeds and a biologically effective amount of a compound of formula 1 and its genomic salts (for example, as a formulated composition) with specific characteristics of germination A Turn seed 'including those performance = vertebra, insect; poison =:=== (its mention S for the current grass: grass, etc.

S 156 201204254 A method of seed treatment by administering a compound of the invention (i.e., a formulated composition) to the seed by spraying or dusting prior to sowing. Compositions for seed treatment are typically formulated, including film formers or binders. Thus, the seed 5 coated with the composition of the present invention typically comprises a biologically effective amount of a compound of formula 1, an N-oxide or a salt thereof, and a film former or binder. Thus, the treatment using the composition comprises coating the seed with a compound of formula i, an oxide thereof or a salt thereof (i.e., in a biologically effective amount), a compound of the formula 1, a N•oxide thereof or a salt thereof. A composition such as a film-forming agent or a binder is formulated. The seed can be applied by spraying the suspension concentrate directly onto the tumbling bed of the seed, followed by drying the seed. Alternatively, other formulation types such as wet powders, solutions, suspoemulsions, emulsifiable emulsifiers and emulsions are sprayed onto the seeds. This process applies a special spray to the film coating of the seed; a variety of coating machines and methods are available to those of ordinary skill in the art. Suitable methods include those listed in p. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57 and the references listed therein. The treated seed typically comprises a compound of the invention in an amount of from about ιg to 1 kg per 100 kg of seed (i.e., from about 20 0.0001 to 1 weight percent of pre-treated seed) to provide biological effectiveness. the amount. Suspension formulations for seed treatment typically comprise from about 5 to 70% active ingredient, from 0.5 to 30% film-forming adhesive, from 5 to 20% dispersant, from 0 to 5% thickener, to 5% pigment and / or dye, 0 to 2% antifoam, 〇 to 1% preservative and 〇 to 75% volatile 25 liquid diluent. 157 201204254 The compounds of the invention may be incorporated into inducing compositions for use by invertebrate pests or in devices such as traps, bait tables and the like. Such a bait composition may be in the form of granules comprising a living = ingredient 'i.e., a biologically effective amount of a compound of formula 1, an N-oxide or a basin salt thereof; (b) one or more food materials; ^, agent; and selective (d) - or a variety of humectants. Notably, the mash comprises between about 0.001 and 5% active ingredient, about 4 ounces to the food material and/or lead; and optionally about (10) to 1 (%) protection: the granule or bait composition, which is at the extreme Soil invertebrate pests can be controlled at low application rates, especially at doses of active ingredients that are fatal by ingestion rather than by direct contact. Some food materials can act as both food and attractants. Food materials include carbohydrates, protein and glutinous. Examples of food materials are vegetable flour, sugar, starch, animal fat, vegetable oil, yeast extract and milk solids. Examples of attractants are gas odorants and fragrances, such as fruit or plant extracts, flavors or other animal or plant components, pheromones or other agents known to attract target invertebrate pests. Examples of humectants (i.e., moisture retaining agents) are diols or other polyols, glycerin, and sorbitol. Of note is a bait composition (and a method of using the bait composition) for controlling at least one invertebrate pest selected from the group consisting of ants, white sacrifice and cockroaches. A device for controlling an invertebrate pest can comprise a tempting composition of the present invention and a % other than the accommodating composition, wherein the outer casing has at least one opening, the opening being sized to allow the The vertebrate pest passes through the opening such that the invertebrate pest can approach the bait composition from a location external to the outer casing, and wherein the

S 158 201204254 . The outer casing is further adapted to be placed at or near the site of potential or known activity of the ridgeless pusher pest. The compounds of the present invention can be administered without other adjuvants, but the most common application is a formulation comprising - or a plurality of active ingredients with suitable hydrazines, diluents and surfactants' and depending on the intended end use It may be combined with food. A method of financing includes spraying an aqueous dispersion or a refined oil solution of a compound of the present invention. Synergistic effects with spray oils, spray oil concentrates, binders, adjuvants, other solvents, and, for example, geranium-based butyrate generally enhance compound efficacy. For non-agricultural drum 10 applications, such sprays may be sprayed from, for example, cans, bottles or other outer casing; the outer casing, by means of a pump or by releasing it from a pressurized outer casing (for example, a pressurized aerosol spray can) Apply. The spray compositions can take a variety of forms such as sprays, mists, foams, fumes or mists. Therefore, the composition of the composition is more likely to lose the propellant, the foam medium, etc. 15 ^ It is worth noting that the effective amount of the package t is the same as that of the mouth. One of such spray compositions = examples of the compounds or compositions of the present invention and two ==; not limited to) toxin, ethylene, butyl, ketone, isopentane, neopentane, ^ 20 Compounds, gas fluorocarbons - _μu 虱 反, 兰 沾 a a ^ ~ methyl ether and a mixture of substances. It is worthwhile to::, 疋-species to control at least one type of spray composition selected from the group of invertebrates (four) (and two, the fog shell to apply this _ hybrid method): , deer flies, horse flies, wasps, small wasps, bumblebees: ',,,:, 25 ants, cockroaches and similar pests, including individual or combination. Monument, insect known spider, 159 201204254 Objects, including (four) secret (specifically, the spine moves t such as: mammals or insects infested, two: 1) from invertebrates (ie bio-desire (four) animal killing The compound of the present invention in biologically effective &gt; (usually formulated as a light-weight material). The method of occlusion is as follows: the method comprises administering the animal parasiticidally effective == two: Γ1 as disclosed in the disclosure and the scope of the patent application As stated, the "10 15 20" and "parasitic ground" mean the effect observed on invertebrate parasites: insects to provide protection against pests. The effect of parasitic killing is to reduce the target. Invertebrate parasitic pests m activity. Such effects on pests include necrotic death, growth retardation, decreased motility or decreased ability to maintain or be in the host animal, reduced feeding and inhibition of reproduction. In the effect of vertebrate parasitic pests, it provides control (including prevention, reduction or elimination) of parasitic infections or infections of animals. By administering a parasiticidally effective amount of a compound of the invention to an animal to be protected Examples of invertebrate parasitic diseases to be controlled include, in particular, ectoparasites (arthropods, cockroaches, etc.). In particular, the compounds of the present invention are effective against ectoparasites, including: cans, such as blood-sucking tanks (scrabble angles) (Lyperosia irritans), 〇 蝇 〇 (St〇m〇xys calcitrans) (廄), mul (Simulium spp.) (black rope), genus Glossinaspp (Glossinaspp·) ), Hydrotaea irritans (head rope), Musca autumnalis (face rope), Musca domestica (Housefly), Morellia simplex (sweat), 妃: Genus (Tabanus spp.) (horse rope), cowhide rope (Hypoderma 25 201204254 bovis), Hypoderma lineatum, Lucilia sericata, Lucilia cuprina (green rope), Blowfly Genus (Calliphoraspp.) (Lilyo), Protophormia spp., sheep nose rope (nasal horse rope), Culicoides spp. 5 (蠓), Horseshoe rope (Hippobosca equine) , Gastrophilus, Gastrophilus haemorrhoidalis and Gastrophilus naslis; for example, Bovicola (Damalinia bovis) 'Bovicolaequi, Haematopinus asini, Felicola subrostratus, Heterodoxus spiniger ), Lignonathus setosus and Trichodectes canis; monuments such as Melophagus ovinus; snails such as Psoroptes spp., Sarcoptes scabei, and cattle Chorioptes bovis, Demodex equi, Cheyletiella spp., Notoedrescati, Trombulaspp. and Otodectes cyanotis (cochlea); 蜱, such as Ixodesspp., Boophilus spp., Rhipicephalus spp., Amblyomma spp., Dermacentor spp .), Hyalomama spp_ and Haemaphysalis spp.; and 蚤 such as cat cephal (Ctenocephalides felis) and dog ticks (Ctenocephalides canis). Non-agronomic applications in the veterinary department are performed in a conventional manner, such as by using in the form of, for example, lozenges, capsules, beverages, watering preparations, granules, serum, boli, via feeding procedures or suppositories. 161 201204254 = by parenteral administration 'such as by injection (including muscle_, subcutaneous, intra-, intraperitoneal) or planting a person; by nasal administration; by topical soaking or impregnation, Spray, wash, spray coating or a smaller area of 5 10 15 20 j, and articles (such as neck rings, earrings, tail bands, limbs) containing the chemicals &amp; compositions or compositions of the present invention Or reins). A typical parasiticidal composition according to the invention, comprising a compound of formula 1 as an N-oxide or a salt thereof, and in one or more pharmaceutically or veterinary acceptable carriers, including adjuvants selected for the route of administration And adjuvants (such as oral, topical or non-oral, such as injection), and in accordance with standard practice. Topical administration provides the best therapeutic indication. In addition, suitable carriers are selected based on the phase of the phase with one or more of the active ingredients in the composition, including factors such as stability relative to pH and moisture content. Accordingly, it is worth noting that a composition for protecting an animal from invertebrate parasitic pests comprises a parasiticidally effective amount of a compound of the invention and at least one carrier. For parenteral administration including intravenous, intramuscular and subcutaneous injection, the compounds of the invention may be formulated as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain, for example, suspensions, stabilizers And/or additives to the dispersant. The pharmaceutical composition for injection comprises an aqueous solution of a water-soluble form of a living ingredient (for example, a salt of the active compound), preferably a physiologically compatible buffer containing other excipients or auxiliaries known in the pharmaceutical formulation technique. Aqueous solution in the middle. For solutions (in the form most readily available for absorption), emulsions, suspensions, pastes, gels, capsules, lozenges, large pills, powders, granules, rumen retentate and feed/water/lickblocks Form

S 162 25 201204254

A crushing agent (for example, crosslinked polyvinylpyrrolidone, agar, brown bath acid) and a dye or pigment. Pastes and gels also typically contain (e.g., gum arabic, alginic acid, bentonite, cellulose, sansonic, colloidal aluminum magnesium citrate) to help keep the composition in contact with the oral cavity and are not easily ejected. If the parasiticidal composition is in the form of a feed concentrate, the carrier is typically selected from the group consisting of high performance feeds, feed mites or protein concentrates. In addition to the insecticidal active ingredient, the compositions containing the feed concentrate may comprise additives which promote the health or growth of the animal, improve the meat quality of the slaughtered animal or otherwise be suitable for use in the livestock industry. Such additives may include, for example, vitamins, antibiotics, chemotherapeutic agents, bacteriostats, fungicides, coccidiostats, and hormones. The compounds of the invention may have advantageous pharmacokinetic and pharmacological properties, providing system availability from oral administration and ingestion. Thus, the compound of the invention at a concentration effective to kill the parasite in the bloodstream after ingestion by the animal to be protected protects the treated animal from blood-sucking pests such as fleas, ticks and ticks. Therefore, it is worth noting that a composition for the purpose of protecting animals from invertebrate parasitic pests for administration via 163 201204254 (i.e., in addition to the compound of the invention for killing parasitic effects) also includes - or a plurality of carriers selected from the group consisting of binders suitable for transfusion and fillers and feed concentrate carriers). Formulations for topical administration are usually in the form of a powder, a milk, a suspension, a spray, a milk, a gas, an ointment, an ointment or a gel. The topical formulation is more typically a water soluble solution which may be in the form of a concentrate which is diluted prior to use. A parasiticidal group suitable for topical administration typically comprises a compound of the invention and one or more topically suitable &amp; agents. The active ingredient migrates over the surface of the animal to cover most or all of the surface of the animal during topical application of the parasiticidal composition to the appearance of the animal in the form of a line or spot (ie, 'spot_on' treatment). Surface area. Thus, treated animals are particularly protected from invertebrate pests (such as ticks, fleas and ticks) that feed on the epidermis of animals. Thus, formulations for topical administration typically comprise at least one organic solvent which facilitates migration of the active ingredient onto the skin and/or penetration into the epidermis of the animal. Solvents generally used as carriers include: propylene glycol, diol 'paraffin, aromatics, S (such as isopropyl myristate), glycol linkages, alcohols (such as ethanol and n-propanol). The rate of application required to achieve effective control (ie, "biologically effective amount") will depend on the species of the invertebrate to be controlled, the life cycle of the pest, the stage of life, its size, location, season, host &amp; animal or animal , feeding behavior, mating behavior, ambient humidity, temperature and other similar factors. Under normal circumstances, in the agronomic ecosystem, an active ingredient of about 0.01 to 2 kg per hectare is sufficient to control pests, but a small amount such as 0.0001 kg/ha may be sufficient or may require as much as 8 kg/ha. In non-agronomic applications, the range of usage required is from about

S 164 201204254 L0 to 50 mg / m ^ 2, but a small amount such as 〇丨 mg / m ^ 2 may be sufficient or may require as much as 15G mg / m ^ 2 . Those skilled in the art can easily determine the amount of bioavailable required to control the level of parasitic nematodes. ° Generally for veterinary use, a parasitic effective amount of a compound of formula 1, an N-oxide or a salt thereof is administered to an animal to protect it from invertebrate parasitic pests. The effective amount of parasiticidal is the amount of active ingredient required to achieve an observable effect of reducing the occurrence or activity of the target invertebrate parasitic pest. Those skilled in the art will appreciate that effective doses of parasiticidal agents can be various compounds and compositions of the invention, required parasiticidal effects and duration of achievement, target invertebrate pest species, animals to be protected, modes of administration, and the like. The amount required to change and achieve a particular result can be determined by simple experimentation. For oral administration to a warm-blooded animal, the daily dose of the compound of the present invention is usually in the range of from about 0.01 mg to about 1 mg per kg of animal body weight, more usually about 0.5 mg per kg of animal body weight. Within the range of about 1 〇〇mg. For topical (e.g., transdermal) administration, the infusion and mouth mist typically contain from about 0.5 ppm to about 5000 ppm, more typically from about 1 ppm to about 3000 ppm of the compound of the invention. The following tests illustrate the control efficacy of the compounds of the invention against specific pests. "Control effectiveness" means inhibition of invertebrate pest development (including death), resulting in a significant reduction in food intake. However, the pest control protection provided by this compound is not limited to these species. For compound descriptions, please index Tables A through F. The following abbreviations are used in the slings. The compound No. represents the compound number, ph is a phenyl group, and the Py system is a bite group. The abbreviation "Ex·" means "instance", and the following number means an example of the compound 165 201204254 process. A dash ("-") in the (R3)n column indicates that the R3 substituent does not exist.

Index table A

Compound number A1 A2 A3 Ri (R3)n R4 R6 mp (°C ) 1 (Example 1) N cf3-c HC 2-Cl-4-Py — H 4-Cl-Ph 100-102 2 (Example 2) HC C1-C Cl-C 2-Cl-4-Py - H 4-Cl-Ph * * 3 (Example 3) HC C1-C Cl-C 2-Cl-4-Py _ H 4-Cl-Ph ** (Note 1) 4 HC HC F3C-C 2-Cl-4-Py - H 4-Cl-Ph 5 HC Cl-C HC 2-Cl-4-Py - H 4-Cl-Ph * 6 HC FC HC 2-Cl-4-Py - H 4-Cl-Ph * 7 HC Cl-C HC 2-CI-4-Py - Me 4-Cl-Ph * 8 HC cf3-c HC 2-Cl-4-Py - H 4-Cl-Ph * 9 HC Cl-C Cl-C 2-Cl-4-Py - Me 4-Cl-Ph * 10 HC cf3-c HC 2-Cl-4-Py - Me 4-Cl-Ph * 11 HC HC F3C-C 2-Cl-4-Py - Me 4-Cl-Ph * 12 HC FC HC 2-Cl-4-Py - Me 4-Cl-Ph 氺13 N Cl-C HC 2-Cl -4-Py - H 4-Cl-Ph * 14 N Cl-C HC 2-Cl-4-Py - H 4-Br-Ph * 15 HC Cl-C HC 2-Cl-4-Py 3-Me H 4-Cl-Ph 16 (Example 4) N HC Cl-C 2-Cl-4-Py - H 4-Cl-Ph 氺 Ben 17 (Example 6) N Cl-C HC 2-Cl-4-Py - Me 4-Cl-Ph ** 18 N HC Cl-C 4-Py - H 4-Cl-Ph 134-136 19 N HC Cl-C 2,6-di-Cl-4-Py — H 4-Cl-Ph 157-159

S 166 201204254 Compound number A1 A2 A3 R1 (R3)n R4 R6 mp (°C ) 20 N C1-C Cl-C 2-Cl-4-Py - Me 4-Cl-Ph * 21 N HC f3c-c 2 -Cl-4-Py - H 4-Cl-Ph * 22 N HC f3c-c 2-Cl-4-Py - Me 4-Cl-Ph * 23 N C1-C HC 2-Cl-4-Py — H 3-Cl-Ph Ben 24 N C1-C HC 2-Cl-4-Py - H 2-Cl-Ph * 25 N C1-C HC 2-Cl-4-Py — H 3-CF3-Ph * 26 N C1-C HC 2-Cl-4-Py - H 4-F-Ph Wood 81 N C1-C Cl-C 2-Cl-4-Py — H 4-Cl-Ph * 82 N Br-C Cl-C 2-Cl-4-Py - H 4-Cl-Ph * 83 N HC Br-C 2-Cl-4-Py - H 4-Cl-Ph * 84 N HC FC 2-Cl-4-Py — H 4 -Cl-Ph Ben 85 N Cl-C FC 2-Cl-4-Py - H 4-Cl-Ph * 86 N Cl-C Br-C 2-Cl-4-Py-H 4-Cl-Ph * 87 N Br-C FC 2-Cl-4-Py — H 4-Cl-Ph 88 N Br-C Br-C 2-Cl-4-Py — H 4-CI-Ph Lucky 89 N Br-C f3c- c 2-Cl-4-Py - H 4-Cl-Ph 90 N Cl-C f3c-c 2-Cl-4-Py - H 4-Cl-Ph % 91 N FC Cl-C 2-Cl-4 -Py - H 4-Cl-Ph * 92 (Example 7) N h2n-c Cl-C 2-Cl-4-Py — H 4-Cl-Ph * t 93 HC Cl-C Cl-C 2-Cl- 4-Py - H 6-Cl-2-Py * 94 N f3c-c HC 2-Cl-4-Py — H 5-Cl-2-Py Wood 95 N f3c-c HC 2-Cl-4-Py - H 6-Cl-2-Py * % ( Example 8) NN Cl-C 2-Cl-4-Py — H 4-Cl-Ph Book 97 N f3c-c HC 2-Br-4-Py - H 4-Cl-Ph * 98 N f3c-c HC 2 , F-4-Py - H 4-Cl-Ph * 99 N f3c-c HC 3-Cl-4-Py — H 4-Cl-Ph * 100 N f3c-c HC 2,3-di-Cl-4 -Py - H 4-Cl-Ph * 101 N f3c-c HC 2-F3C-4-Py - H 4-Cl-Ph 氺102 N f3c-c HC 2-Cl-3-F-4-Py - H 4-Cl-Ph * 103 N f3c-c HC 2-Cl-4-Py 2-Me H 4-Cl-Ph * 104 HC f3c-c N 2-Cl-4-Py - H 4-Cl-Ph Umbrella 105 N f3c-c HC 4-pyrimidinyl-H 4-Cl-Ph * 106 HC Cl-C FC 2-Cl-4-Py — H 4-Cl-Ph * 167 201204254 Compound number A1 A2 A3 R1 (R3) n R4 R6 mp (°C) · 107 HC Br-C FC 2-Cl-4-Py - H 4-Cl-Ph This « 108 N f3c-c HC 2-C1-5-thiazolyl — H 4- Cl-Ph * • 109 N Cl-C FC 2-Cl-4-Py - Me 4-Cl-Ph * _ 110 N Br-C FC 2-Cl-4-Py - Me 4-Cl-Ph * 111 NN Br-C 2-Cl-4-Py - H 4-Cl-Ph Note 1: Compound 2 oxalate. * See the index table G for hNMR data. **] HNMR data can be found in the synthesis example.

Index table B

NH Compound Number A1 A2 A3 R1 R6 mp (°C) 27 HC HC cf3-c 2-Cl-4-Py 4-F-Ph 氺28 HC HC cf3-c 2-Cl-4-Py 4-F-Ph (Note 2) 29 HC Cl-C Cl-C 2-Cl-4-Py 4-F-Ph 氺30 HC Cl-C Cl-C 2-Cl-4-Py 4-Cl-Ph 氺31 HC Cl- C HC 2-Cl-4-Py 4-F-Ph 氺32 HC FC HC 2-Cl-4-Py 4-F-Ph 氺33 HC Cl-C HC 2-Cl-4-Py 4-Cl-Ph * 34 HC FC HC 2-Cl-4-Py 4-Cl-Ph 氺35 N cf3-c HC 2-Cl-4-Py 4-F-Ph 氺36 N Cl-C Cl-C 2-Cl-4 -Py 4-F-Ph 氺37 N Br-C Cl-C 2-Cl-4-Py 4-F-Ph 氺

S 168 201204254 Note 2: Compound HCl salt of Compound 27. * See the index table G for WNMR data. ** 1H NMR data can be found in the synthesis example.

Index table C

Compound No. A1 A2 A3 R1 R4 R34 R6 mp (°C ) 38 HC HC f3c-c 2-Cl-4-Py HH 4-F-Ph This 39 HC C1-C HC 2-Cl-4-Py HH 4- F-Ph * 40 HC C1-C Cl-C 2-Cl-4-Py HH 4-F-Ph * 41 HC f3c-c HC 2-Cl-4-Py HH 4-F-Ph * 42 HC FC HC 2-Cl-4-Py HH 4-F-Ph Ben 43 HC C1-C HC 2-Cl-4-Py HH 4-Br-Ph * 44 HC C1-C HC 2-Cl-4-Py HH 4- Cl-Ph this 45 HC C1-C Cl-C 2-Cl-4-Py HH 4-Cl-Ph * 46 HC f3c-c HC 2_Cl_4_Py HH 4-Cl-Ph * 47 HC HC F3C-C 2_Cl_4_Py HH 4- Cl-Ph wood 48 HC FC HC 2-Cl-4-Py HH 4-Cl-Ph * 49 HC Cl-C HC 2-Cl-4-Py Me H 4-F-Ph * 50 N HC Cl-C 2 -Cl-4-Py HH 4-F-Ph * 51 N Cl-C HC 2-Cl-4-Py HH 4-F-Ph * 52 N Cl-C HC 2-Cl-4-Py HH 4-Cl -Ph * 53 N Cl-C HC 2-Cl-4-Py Me H 4-F-Ph * 54 HC Cl-C HC 2-Cl-4-Py HH 3-F-Ph This 55 HC Cl-C HC 2-Cl-4-Py HH 2,4-di-F-Ph 56 HC Cl-C HC 2-Cl-4-Py HH 3,4-di-F-Ph * 169 201204254 Compound number A1 A2 A3 R1 R4 R34 R6 mp (°C) 57 N Cl-C Cl-C 2-Cl-4-Py HH 4-F-Ph * 58 N Cl-C Cl-C 2-Cl-4-Py HH 4-Cl- Ph * 59 N f3c-c HC 2-Cl- 4-Py HH 4-F-Ph * 60 N f3c-c HC 2-Cl-4-Py HH 4-Cl-Ph 氺61 HC Cl-C Cl-C 2-Cl-4-Py HH 3-F- Ph * 62 HC Cl-C Cl-C 2-Cl-4-Py HH 2,4-di-F-Ph * 63 HC Cl-C Cl-C 2-Cl-4-Py HH 3,4-di- F-Ph * 64 HC Cl-C HC 2-Cl-4-Py HH 3-Cl-Ph This 65 HC Cl-C HC 2-Cl-4-Py HH 5-Cl-2-Py * 66 N f3c- c HC 2-Cl-4-Py HH 3-F-Ph This 67 N f3c-c HC 2-Cl-4-Py HH 2,4-di-F-Ph * 68 N f3c-c HC 2-Cl- 4-Py HH 3,4-di-F-Ph Ben 69 N f3c-c HC 2-Cl-4-Py HH 5-Cl-2-Py * 70 HC Cl-C Cl-C 2-Cl-4- Py HH 5-Cl-2-Py 71 N f3c-c HC 2-Cl-4-Py H Me 4-F-Ph * 72 N Cl-C Cl-C 2-Cl-4-Py H Me 4-F -Ph * 73 N Cl-C HC 2-Cl-4-Py H Me 4-F-Ph * 74 HC Cl-C HC 2-Cl-4-Py HH 2-Cl-4-F-Ph * 75 HC Cl-C HC 2-Cl-4-Py HH 2-F-4-Cl-Ph * 76 HC Cl-C HC 2-Cl-4-Py HH 2,4-di-Cl-Ph * 77 HC Cl- C Cl-C 2-Cl-4-Py HH 2-Cl-4-F-Ph * 78 HC Cl-C Cl-C 2-Cl-4-Py HH 2_F_4-Cl-Ph * 79 HC Cl-C Cl -C 2-Cl-4-Py HH 2,4-di-Cl-Ph Ben 80 (Example 5) N Cl-C Cl-C 2-CM-Py HH 4-Br-Ph * * 112 N HC Br- C 2-Cl-4-Py HH 4-F-Ph * 113 N HC Br-C 2-Cl -4-Py HH 4-Cl-Ph * 114 N HC Br-C 2-Cl-4-Py HH 4-Br-Ph * 115 N HC Br-C 2-Cl-4-Py HH 2,4-di -F-Ph Ben 116 N Cl-C HC 2-Cl-4-Py HH 2,4-di-F-Ph 117 N Cl-C HC 2-Cl-4-Py HH 2-Cl-4-F- Ph Ben 118 N Cl-C HC 2-Cl-4-Py HH 2-F-4_Cl-Ph * 119 N Cl-C HC 2-Cl-4-Py HH 2,4-di-Cl-Ph * 120 N Cl-C HC 2-Cl-4-Py HH 4-Br-Ph

S 170 201204254 Compound number A1 A2 A3 R1 R4 R34 R6 mp (°C) 121 N f3c-c HC 2-Cl-4-Py HH 2,4-di-Cl-Ph * 122 N f3c-c HC 2-Cl -4-Py HH 2 Winter 4-Cl-Ph * 123 N f3c-c HC 2-Cl-4-Py HH 2-Cl-4-F-Ph Lucky 124 N HC Cl-C 2-Cl-4-Py HH 2-F-4-F-Ph * 125 N HC Cl-C 2-Cl-4-Py HH 4-Br-Ph * 126 N HC Cl-C 2-Cl-4-Py HH 4-Cl-Ph * 127 N Cl-C Cl-C 2-Cl-4-Py HH 2,4-di-F-Ph * 128 N HC FC 2-Cl-4-Py HH 4-Cl-Ph * 129 N HC f3c- c 2-Cl-4-Py HH 2,4-di-F-Ph * 130 N HC f3c-c 2_C1_4-Py HH 4-Br-Ph * 131 N HC f3c-c 2-Cl-4-Py HH 4 -Cl-Ph * 132 N HC f3c-c 2-Cl-4-Py HH 4-F-Ph * 133 N HC Br-C 2-Cl-4-Py H Me 4-F-Ph * 134 N HC Cl -C 2-Cl-4-Py H Me 4-F-Ph * 135 N HC FC 2-Cl-4-Py H Me 4-F-Ph * 136 N HC f3c-c 2-Cl-4-Py H Me 4-F-Ph * 137 N F3C-C HC 2-Cl-4-Py HH 4-MeO-Ph Wood 138 N f3c-c HC 2-Cl-4-Py HH 4-02N-Ph * 139 N f3c -c HC 2-Cl-4-Py HH 4-F3CO-Ph Ben 140 N f3c-c HC 2-Cl-4-Py HH 4-NC-Ph * 141 N f3c-c HC 2-Cl-4-Py HH 4-t-Bu-Ph * 142 N f3c-c HC 2-Cl-4-Py HH 4-F3C-Ph * 143 N HC Cl-C 2-Cl-4-Py H Me 4-Cl-Ph * 144 N Cl-C F3C-C 2-Cl-4-Py HH 4-F-Ph * 145 N Cl-C f3c-c 2-Cl-4-Py HH 4-Cl-Ph 146 N Cl-C f3c-c 2-Cl-4-Py HH 4-Br-Ph 147 N Cl-C FC 2-Cl-4-Py H Me 4-Cl-Ph * 148 N Cl-C F3C-C 2-Cl-4-Py H Me 4-Cl-Ph Ben 149 N Cl-C Br-C 2-Cl-4-Py H Me 4-Cl -Ph 150 N Cl-C Br-C 2-Cl-4-Py HH 4-F-Ph * 151 N Cl-C Br-C 2-Cl-4-Py HH 4-Cl-Ph * 152 N Cl -C Br-C 2-Cl-4-Py HH 4-Br-Ph * 153 N Cl-C FC 2-Cl-4-Py HH 4-Cl-Ph * 171 201204254 Compound number A1 A2 A3 R1 R4 R34 R6 Mp (°C) 154 N Cl-C FC 2-Cl-4-Py HH 4-Br-Ph * 155 N Cl-C FC 2-Cl-4_Py HH 4-F-Ph * 156 N Br-C FC 2 -Cl-4-Py HH 4-Br-Ph * 157 N Br-C FC 2-Cl-4-Py HH 4-Cl-Ph * 158 N Br-C FC 2-Cl-4-Py HH 4-F -Ph * 159 N Br-C F3C-C 2-Cl-4-Py H Me 4-Cl-Ph * 160 N Br-C Br-C 2-Cl-4-Py H Me 4-Cl-Ph * 161 N Br-C Cl-C 2-Cl-4-Py H Me 4-Cl-Ph * 162 N Br-C FC 2-Cl-4-Py H Me 4-Cl-Ph * 163 N F3C-C HC 2 -Cl-4-Py H Et 4-Cl-Ph 氺164 N Br-C Br-C 2_Cl-4-Py HH 4-Br-Ph * 165 N Br-C Br-C 2-Cl-4-Py H H 4-Cl-Ph * 166 N Br-C Br-C 2-Cl-4-Py HH 4-F-Ph * 167 N Br-C Cl-C 2-Cl-4-Py HH 4-Br-Ph * 168 N Br-C Cl-C 2-Cl-4-Py HH 4-Cl-Ph 169 N Br-C Cl-C 2-Cl-4-Py HH 4-F-Ph * 170 N Br-C F3C-C 2-Cl-4-Py HH 4-Cl-Ph * 171 HC Cl-C Cl-C 2-Cl-4-Py H Me 5-Cl-2-Py * 172 N f3c-c HC 2- Cl-4-Py H Me 5-Cl-2-Py * 173 HC Cl-C Cl-C 2-Cl-4-Py HH 6-Br-3-Py * 174 N f3c-c HC 2-Cl-4 -Py HH 6-C1-3-.荅【口+井】基氺175 HC Cl-C Cl-C 2-Cl-4-Py HH 6-Cl-3-Py * 176 HC Cl-C Cl-C 2-Cl-4-Py HH 6- C1-3-嗒[口+井]基* 177 N f3c-c HC 2-Cl-4-Py HH 6-Cl-3-Py * 178 N f3c-c HC 2_Cl-4_Py HH 6-Br-3- Py * 179 N f3c-c HC 2-Cl-4-Py H Me 4-Cl-Ph * 180 N FC Cl-C 2-Cl-4-Py H Me 4-Cl-Ph Ben 181 N FC Cl-C 2-Cl-4-Py HH 4-Cl-Ph * 182 HC Cl-C Cl-C 2-Cl-4-Py HH 5-Br-2-Py * 183 N f3c-c HC 2-Cl-4- Py HH 5-Br-2-Py Ben 184 HC Cl-C Cl-C 2-Cl-4-Py HH 2-Cl-4-Py Ben 185 N f3c-c HC 2-Cl-4-Py HH 2- Cl-4-Py 氺s 172 201204254 Compound number A1 A2 A3 R1 R4 R34 R6 mp (°C) 186 HC C1-C Cl-C 2-Cl-4-Py HH 5-C1-2-pyrimidinyl* 187 N F3c-c HC 2-Cl-4-Py HH 5-C1-2-pyrimidinyl* 188 NN Cl-C 2-Cl-4-Py H Me 4-Cl-Ph * 189 N f3c-c HC 2-Br -4-Py H Me 4-Cl-Ph * 190 N f3c-c HC 2-Br-4-Py HH 4-Cl-Ph * 191 N f3c-c HC 2-Br-4-Py HH 4-F- Ph * 192 N f3c-c HC 2-F-4-Py H Me 4-Cl-Ph 193 N f3c-c HC 2-F-4-Py HH 4-Cl-Ph 幸194 N f3c-c HC 2 -F-4-Py HH 4-F-Ph * 195 N f3c-c HC 3- Cl-4-Py H Me 4-Cl-Ph * 196 N f3c-c HC 2,3-di-Cl-4-Py H Me 4-Cl-Ph Ben 197 N f3c-c HC 2,3_di-Cl- 4-Py HH 4-Cl-Ph * 198 N f3c-c HC 2,3-di-Cl-4-Py HH 4-F-Ph * 199 N f3c-c HC 3-Cl-4-Py HH 4- F-Ph * 200 N f3c-c HC 3-Cl-4-Py HH 4-Cl-Ph * 201 N f3c-c HC 2-F3C-4-Py H Me 4-Cl-Ph * 202 N f3c-c HC 2-Cl-3-F-4-Py H Me 4-Cl-Ph 203 N f3c-c HC 2-C1-4-pyrimidinyl H Me 4-Cl-Ph * 204 N f3c-c HC 2- Cl-3-F-4-Py HH 4-Cl-Ph 205 HC f3c-c N 2-Cl-4-Py H Me 4-Cl-Ph Ben 206 N f3c-c HC 4- 嗔 嗔 H H Me 4-Cl-Ph * 207 N f3c-c HC 4-pyrimidinyl HH 4-Cl-Ph 208 HC Cl-C Cl-C 2-Cl-4-Py HH 5-F-2-Py 209 N f3c -c HC 2-Cl-4-Py HH 5-F-2-Py Ben 210 HC Cl-C FC 2-Cl-4-Py H Me 4-Cl-Ph * 211 HC Br-C FC 2-Cl- 4-Py H Me 4-Cl-Ph This 212 NN Br-C 2-Cl-4-Py H Me 4-Cl-Ph * * i NMR data can be found in index table G. ** 1H NMR data can be found in the synthesis example.

Index Table D 173 201204254 Η

Compound number A1 A2 A3 A4 R1 R2 T R6 mp (°C ) 213 HC C1-C HC HC 2-Cl-4-Py HS 4-Cl-Ph * 214 N f3c-c HC HC 2-Cl-4-Py H NH 4-Cl-Ph * 215 N f3c-c HC HC 2-Cl-4-Py Me 0 4-Cl-Ph 氺216 N Br-C HC N 2-Cl-4-Py H 0 4-Cl- Ph * 217 N Cl-C HC N 2-Cl-4-Py H 0 4-Cl-Ph 氺218 N Cl-C Cl-C N 2-Cl-4-Py H 0 4-Cl-Ph * * hNMR See the index table G for data.

Index table Er 34

Compound mp number A1 A2 A3 A4 R1 R2 R34 Z R6 (°C) 219 N f3c-c HC HC 2-CM-Py HH NH 4-Cl-Ph 氺220 N f3c-c HC HC 2-Cl-4-Py Me Me 0 4-Cl-Ph 氺221 N f3c-c HC HC 2-Cl-4-Py HH NMe 4-Cl-Ph 氺222 N f3c-c HC HC 2-Cl-4-Py Me H 0 4- Cl-Ph 氺223 N Br-C HC N 2-Cl-4-Py H Me 0 4-Cl-Ph 氺224 N Cl-C Cl-C N 2-Cl-4-Py H Me 0 4-Cl- Ph 氺

S 174 201204254 W NMR data can be found in index table G.

Index table F

Compound number A1 A2 A3 A1 2 R1 st R3 4 5 mp (°C) 225 N f3c-c HC HC 2-Cl-4-Py 3 1 4-Cl-Ph 氺226 N f3c-c HC HC 2-Cl- 4-Py 2 2 4-Cl-Ph * 227 N f3c-c HC HC 2-Cl-4-Py 2 1 4-Cl-Ph * ^ NMR data can be found in index table G.

Index Table G Compound Number hNMR data (unless otherwise stated, all refer to CDC13 solution) a 175 1 δ 8. 81 (d, 1H), 8. 61 (d, 1H), 8. 57 (br s, 1H), 7. 80 (d, 1H), 7. 65 (dd, 1H), 7. 37 (dd, 1H), 7. 28 (s, 4H), 6. 75 (d, 1H), 6. 50 (d, 1H), 6. 13 (dt, 1H), 4. 97 (m, 1H), 3. 85 (m, 1H), 3. 35-3. 29 (m, 4H).  2 δ 8. 58 (d, 1H), 8. 46 (br s, 1H), 8. 41 (d, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 28 (s, 4H), 7. 04 (dd, 1H), 6. 66 (d, 1H), 6. 49 (d, 1H), 6. 12 (dt, 1H), 4. 88 (m, 1H), 3. 82 (m, 2H), 3. 35-3. 29 (m, 4H).  3 δ 8. 58 (d, 1H), 8. 40 (dd, 1H), 8. 36 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 28 (s, 4H), 6. 77 (dt, 1H), 6. 50 (d, 1H), 6. 43 (dd, 1H), 6. 12 (dt, 1H), 4. 87 (m, 1H), 3. 83 (dd, 2H), 3. 35-3. 29 (m, 4H).  4 δ 8. 59 (d, 1H), 8. 44 (br s, 1H), 8. 40 (d, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 28 (s, 4H), 7. 03 (dd, 1H), 6. 66 (d, 1H), 6. 48 (d, 1H), 5. 98 (dd, 1H), 4. 83 (m, 1H), 3. 80 (m, 1H), 3. 74 (m, 1H), 3. 27 (m, 2H), 3. 01 (pentet, 1H), 1. 16 (d, 3H).  5 δ 8. 66 (s, 1H), 8. 62 (d, 1H), 8. 60 (s, 1H), 7. 82 (d, 1H), 7. 66 (dd, 1H), 7. 35 (d, 1H), 7. 28 (s, 4H), 6. 89 (d, 1H), 6. 50 (d, 1H), 6. 13 (dt, 1H), 4. 96 (m, 1H), 3. 83 (m, 2H), 3. 34 (m, 4H).  δ 8. 64 (s, 1Η), 8. 60 (d, 1H), 8. 47 (br s, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 27 (s, 4H), 6. 74 (s, 1H), 6. 48 (d, 1H), 5. 98 (dd, 1H), 4. 82 (m, 1H), 3. 78 (m, 1H), 3. 72 (m, 1H), 3. 28 (m, 2H), 3. 02 (pentet, 1H), 1. 16 (d, 3H).  δ 8. 64 (s, 1H), 8. 62-8. 58 (m, 2H), 7. 81 (s, 1H), 7. 64 (dd, 1H), 7. 34 (d, 1H), 7. 28 (s, 4H), 6. 88 (d, 1H), 6. 48 (d, 1H), 5. 98 (dd, 1H), 4. 90 (m, 1H), 3. 81 (m, 1H), 3. 75 (m, 1H), 3. 29 (m, 2H), 3. 02 (pentet, 1H), 1. 17 (d, 3H).  δ 8. 79 (s, 1H), 8. 61 (d, 1H), 8. 54 (br s, 1H), 7. 79 (s, 1H), 7. 65 (d, 1H), 7. 36 (dd, 1H), 7. 28 (s, 4H), 6. 75 (d, 1H), 6. 49 (d, 1H), 5. 99 (dd, 1H), 4. 92 (m, 1H), 3. 85 (m, 1H), 3. 78 (m, 1H), 3. 28 (m, 2H), 3. 03 (br s, 1H), 1. 18 (d, 3H).  δ 8. 59 (d, 1H), 8. 42-8. 31 (m, 2H), 7. 79 (s, 1H), 7. 64 (m, 1H), 7. 28 (s, 4H), 6. 76 (td, 1H), 6. 49 (d, 1H), 6. 43 (dd, 1H), 5. 99 (dd, 1H), 4. 83 (m, 1H), 3. 82 (m, 1H), 3. 76 (m, 1H), 3. 27 (m, 2H), 3. 02 (br s, 1H), 1. 17 (d, 3H).  δ 8. 67 (d, 1H), 8. 60 (d, 1H), 8. 32 (br s, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 28 (s, 4H), 7. 00 (d, 1H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 36 (m, 1H), 3. 83 (m, 2H), 3. 36-3. 30 (m, 4H).  δ (acetone-d6) 9. 21 (br s, 1H), 8. 57-8. 53 (m, 2H), 7. 97 (s, 1H), 7. 94 (d, 1H), 7. 48 (d, 2H), 7. 27 (d, 2H), 7. 06 (d, 1H), 6. 74 (d, 1H), 6. 18 (dt, 1H), 5. 57 (m, 1H), 4. 43-4. 25 (m, 4H), 3. 85 (d, 2H).  δ 9. 16 (s, 1H), 8. 55 (d, 1H), 8. 45 (d, 1H), 7. 82 (s, 1H), 7. 66 (d, 1H), 7. 27 (d, 2H), 7. 21 (d, 2H), 7. 08 (dd, 1H), 6. 74 (d, 1H), 6. 40 (d, 1H), 5. 95 (dt, 1H), 3. 43 (d, 2H), 3. 38 (d, 2H), 3. 29 (d, 2H), 1. 72 (s, 3H).  δ 8. 87 (s, 1H), 8. 62 (d, 1H), 8. 30 (br s, 1H), 7. 77 (d, 1H), 7. 63 (d, 1H), 7. 28 (s, 4H), 6. 48 (d, 1H), 6. 00 (dd, 1H), 5. 29 (m, 1H), 3. 80 (m, 1H), 3. 74 (m, 1H), 3. 31 (m, 2H), 3. 01 (br s, 1H), 1. 17 (d, 3H).  δ 9. 0 (s, 1H), 8. 62 (d, 1H), 8. 41 (bs, 1H), 8. 2 (s, 1H), 7. 8 (s, 1H), 7. 65 (d, 1H), 7. 25 (s, 4H), 6. 5 (dd, 1H), 6. 18 (m, 1H), 5. 4 (m, 1H), 3. 9 (m, 2H), 3. 36 (m, 4H).  δ 8. 66 (d, 1H), 8. 61 (d, 1H), 8. 31 (br s, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 28 (s, 4H), 7. 00 (d, 1H), 6. 48 (d, 1H), 6. 01 (dd, 1H), 5. 31 (m, 1H), 3. 78 (m, 2H), 3. 31 (m, 2H), 3. 01 (m, 1H), 1. 16 (d, 3H).  5 8. 66 (d, 1H), 8. 60 (d, 1H), 8. 40 (br s, 1H), 7. 81 (s, 1H), 7. 66 (dd, 1H), 7. 35 (s, 1H), 7. 25-7. 20 (m, 3H), 7. 01 (d, 1H), 6. 50 (d, 1H), 6. 18 (dt, 1H), 5. 39 (m, 1H), 3. 86 (m, 2H), 3. 43 (br s, 2H), 3. 37 (d, 2H).  s 176 201204254 .  24 δ 8. 68 (br s, 1H), 8. 63 (d, 1H), 8. 59 (d, 1H), 7. 88 (s, 1H), 7. 76 (d, 1H), 7. 52 (dd, 1H), 7. 36 (dd, 1H), 7. 25-7. 18 (m, 2H), .  7. 06-6. 98 (m, 2H), 6. 50 (d, 1H), 6. 18 (dt, 1H), 5. 39 (m, 1H), 3. 86 (m, 2H), 3. 43 (br s, 2H), 3. 37 (d, 2H).  25 δ 8. 67 (d, 1H), 8. 61 (d, 1H), 8. 32 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 60 (s, 1H), 7. 53 (d, 1H), 7. 49 (d, 1H), 7. 43 (t, 1H), 7. 01 (d, 1H), 6. 58 (d, 1H), 6. 25 (dt, 1H), 5. 38 (m, 1H), 3. 86 (m, 2H), 3. 40-3. 34 (m, 4H).  26 δ 8. 57 (d, 1H), 8. 53 (d, 1H), 8. 59-8. 47 (br s, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 7. 26 (m, 2H), 6. 96-6. 88 (m, 3H), 6. 47 (d, 1H), 6. 01 (dt, 1H), 5. 33 (m, 1H), 3. 78 (m, 2H), 3. 45-3. 37 (m, 2H), 3. 31 (br d, 2H).  27 5 8. 80 (s, 1H), 8. 61 (d, 1H), 8. 54 (s, 1H), 7. 79 (s, 1H), 7. 64 (d, 1H), 7. 55-7. 49 (m, 4H), 7. 38-7. 33 (m, 3H), 7. 12 (t, 2H), 6. 74 (d, 1H), 4. 97 (m, 1H), 3. 87 (t, 2H), 3. 77 (s, 2H), 3. 32 (m, 2H).  29 δ 8. 65 (s, 1H), 8. 60 (d, 1H), 8. 45 (s, 1H), 7. 78 (s, 1H), 7. 62 (m, 1H), 7. 56-7. 48 (m, 4H), 7. 34 (d, 2H), 7. 12 (t, 2H), 6. 74 (s, 1H), 4. 88 (m, 1H), 3. 83 (m, 2H), 3. 76 (s, 2H), 3. 31 (m, 2H).  30 5 8. 65 (s, 1H), 8. 60 (d, 1H), 8. 44 (br s, 1H), 7. 77 (s, 1H), 7. 62 (d, 1H), 7. 51 (dd, 4H), 7. 40 (d, 2H), 7. 35 (d, 2H), 6. 74 (s, 1H), 4. 88 (m, 1H), 3. 82 (m, 2H), 3. 76 (s, 2H), 3. 30 (m, 2H).  31 δ 8. 59 (d, 1H), 8. 43 (s, 1H), 8. 40 (d, 1H), 7. 78 (s, 1H), 7. 63 (d, 1H), 7. 55-7. 49 (m, 4H), 7. 34 (d, 2H), 7. 12 (t, 2H), 7. 03 (dd, 1H), 6. 66 (d, 1H), 4. 89 (m, 1H), 3. 84 (m, 2H), 3. 76 (s, 2H), 3. 30 (m, 2H).  32 δ 8. 59 (d, 1H), 8. 39 (dd, 1H), 8. 34 (s, 1H), 7. 78 (s, 1H), 7. 63 (d, 1H), 7. 55-7. 49 (m, 4H), 7. 34 (d, 2H), 7. 12 (t, 2H), 6. 76 (ddd, 1H), 6. 43 (dd, 1H), 4. 88 (m, 1H), 3. 85 (t, 2H), 3. 76 (s, 2H), 3. 30 (m, 2H).  33 δ 8. 59 (d, 1H), 8. 46 (s, 1H), 8. 40 (d, 1H), 7. 79 (s, 1H), 7. 63 (d, 1H), 7. 51 (dd, 4H), 7. 40 (d, 2H), 7. 35 (d, 2H), 7. 03 (dd, 1H), 6. 65 (d, 1H), 4. 89 (m, 1H), 3. 83 (m, 2H), 3. 76 (s, 2H), 3. 30 (m, 2H).  34 δ 8. 58 (d, 1H), 8. 39 (dd, 1H), 8. 34 (s, 1H), 7. 78 (s, 1H), 7. 63 (d, 1H), 7. 51 (dd, 4H), 7. 40 (d, 2H), 7. 35 (d, 2H), 6. 76 (ddd, 1H), 6. 43 (dd, 1H), 4. 88 (m, 1H), 3. 85 (t, 2H), 3. 76 (s, 2H), 3. 29 (m, 2H).  35 6 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 50 (br s, 1H), 7. 80 (s, 1H), 7. 65 (m, 1H), 7. 55-7. 49 (m, 4H), 7. 39-7. 34 (m, 3H), 7. 12 (t, 2H), 5. 44 (m, 1H), 3. 89 (t, 2H), 3. 77 (s, 2H), 3. 34 (br s, 2H).  36 δ 8. 87 (s, 1H), 8. 62 (d, 1H), 8. 33 (br s, 1H), 7. 78 (s, 1H), 7. 64 (d, 1H), 7. 55-7. 49 (m, 4H), 7. 36 (d, 2H), 7. 12 (t, 2H), 5. 35 (m, 1H), 3. 85 (m, 2H), 3. 77 (s, 2H), 3. 35 (br s, 2H).  177 δ 8. 84 (s, 1Η), 8. 62 (d, 1H), 8. 31 (br s, 1H), 7. 78 (s, 1H), 7. 63 (d, 1H), 7. 55-7. 49 (m, 4H), 7. 36 (d, 2H), 7. 12 (t, 2H), 5. 36 (m, 1H), 3. 85 (m, 2H), 3. 76 (s, 2H), 3. 34 (br s, 2H).  δ 8. 80 (d, 1H), 8. 61 (d, 1H), 8. 58 (br s, 1H), 7. 79 (d, 1H), 7. 65 (dd, 1H), 7. 38 (dd, 1H), 6. 97 (t, 2H), 6. 82 (m, 2H), 6. 75 (d, 1H), 4. 97 (m, 1H), 3. 99 (t, 2H), 3. 95 (m, 2H), 3. 41 (m, 2H), 2. 96 (t, 2H).  δ 8. 58 (d, 1H), 8. 45 (br s, 1H), 8. 40 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 04 (dd, 1H), 6. 97 (t, 2H), 6. 82 (m, 2H), 6. 66 (d, 1H), 4. 89 (m, 1H), 3. 98 (t, 2H), 3. 92 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  δ 8. 65 (s, 1H), 8. 59 (d, 1H), 8. 46 (br s, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 6. 96 (t, 2H), 6. 82 (m, 2H), 6. 74 (s, 1H), 4. 88 (m, 1H), 3. 98 (t, 2H), 3. 91 (m, 2H), 3. 41 (m, 2H), 2. 96 (t, 2H).  δ 8. 64 (br s, 1H), 8. 62-8. 59 (m, 2H), 7. 81 (d, 1H), 7. 65 (dd, 1H), 7. 35 (d, 1H), 6. 96 (t, 2H), 6. 88 (d, 1H), 6. 82 (m, 2H), 4. 96 (m, 1H), 3. 99 (t, 2H), 3. 94 (m, 2H), 3. 43 (m, 2H), 2. 96 (t, 2H).  δ 8. 58 (d, 1H), 8. 39 (dd, 1H), 8. 36 (br s,1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 6. 96 (t, 2H), 1H), 6. 82 (m, 2H), 6. 77 (dt, 1H), 6. 43 (dd, 1H), 4. 88 (m, 1H), 3. 98 (t, 2H), 3. 93 (m, 2H), 3. 39 (m, 2H), 2. 96 (t, 2H).  δ 8. 59 (d, 1H), 8. 44 (br s, 1H), 8. 40 (d, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 37 (d, 2H), 7. 04 (dd, 1H), 6. 77 (d, 2H), 6. 66 (d, 1H), 4. 89 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 39 (m, 2H), 2. 96 (t, 2H).  δ 8. 58 (d, 1H), 8. 44 (br s, 1H), 8. 40 (d, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 23 (d, 2H), 7. 04 (dd, 1H), 6. 81 (d, 2H), 6. 66 (d, 1H), 4. 88 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 39 (m, 2H), 2. 96 (t, 2H).  δ 8. 64 (s, 1H), 8. 59 (d, 1H), 8. 47 (br s, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 7. 23 (d, 2H), 6. 81 (d, 2H), 6. 74 (s, 1H), 4. 87 (m, 1H), 3. 99 (t, 2H), 3. 90 (m, 2H), 3. 40 (m, 2H), 2. 96 (t, 2H).  δ 8. 63 (br s, 1H), 8. 62-8. 59 (m, 2H), 7. 80 (d, 1H), 7. 65 (dd, 1H), 7. 35 (d, 1H), 7. 23 (d, 2H), 6. 88 (d, 1H), 6. 81 (d, 2H), 4. 96 (m, 1H), 4. 00 (t, 2H), 3. 93 (m, 2H), 3. 42 (m, 2H), 2. 97 (t, 2H).  δ 8. 80 (d, 1H), 8. 60 (d, 1H), 8. 56 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 38 (dd, 1H), 7. 23 (d, 2H), 6. 81 (d, 2H), 6. 74 (d, 1H), 4. 97 (m, 1H), 4. 00 (t, 2H), 3. 95 (m, 2H), 3. 41 (m, 2H), 2. 97 (t, 2H).  δ 8. 58 (d, 1H), 8. 39 (dd, 1H), 8. 35 (br s, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 23 (d, 2H), 1H), 6. 81 (d, 2H), 6. 77 (dt, 1H), 6. 43 (dd, 1H), 4. 87 (m, 1H), 3. 99 (t, 2H), 3. 93 (m, 2H), 3. 39 (m, 2H), 2. 96 (t, 2H).  s 178 201204254 * 49 δ 8. 59 (d, 1Η), 8. 48 (br s, 1H), 8. 40 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 04 (dd, 1H), 6. 97 (t, 2H), 6. 82 (m, 2H), 6. 68 (d, 1H), .  4. 86 (m, 1H), 3. 89 (br m, 2H), 3. 81 (d, 2H), 3. 42 (dd, 1H), 3. 35 (dd, 1H), 2. 80 (m, 1H), 1. 09 (d, 3H).  50 5 8. 76 (d, 1H), 8. 61 (d, 1H), 8. 38 (br s, 1H), 7. 85 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 35 (m, 1H), 3. 98 (t, 2H), 3. 91 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  51 δ 8. 66 (d, 1H), 8. 60 (d, 1H), 8. 34 (br s, 1H), 7. 79 (s, 1H), 7. 63 (dd, 1H), 7. 01 (d, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 38 (m, 1H), 3. 98 (t, 2H), 3. 92 (m, 2H), 3. 43 (br m, 2H), 2. 95 (t, 2H).  52 δ 8. 66 (d, 1H), 8. 60 (d, 1H), 8. 35 (br s, 1H), 7. 79 (s, 1H), 7. 63 (dd, 1H), 7. 23 (d, 2H), 7. 01 (d, 1H), 6. 82 (d, 2H), 5. 38 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 43 (dd, 2H), 2. 95 (t, 2H).  53 δ 8. 66 (d, 1H), 8. 61 (d, 1H), 8. 34 (br s, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 01 (d, 1H), 6. 97 (t, 2H), 6. 82 (m, 2H), 5. 34 (m, 1H), 3. 89 (br m, 2H), 3. 81 (m, 2H), 3. 44 (dd, 1H), 3. 38 (dd, 1H), 2. 79 (m, 1H), 1. 09 (d, 3H).  54 δ 8. 59 (d, 1H), 8. 47 (br s, 1H), 8. 40 (d, 1H), 7. 79 (d, 1H), 7. 63 (dd, 1H), 7. 22 (td, 1H), 7. 04 (dd, 1H), 6. 67 (m, 2H), 6. 66 (d, 1H), 6. 60 (dt, 1H), 4. 89 (m, 1H), 4. 01 (t, 2H), 3. 92 (m, 2H), 3. 40 (m, 2H), 2. 96 (t, 2H).  55 δ 8. 58 (d, 1H), 8. 53 (br s, 1H), 8. 40 (d, 1H), 7. 80 (d, 1H), 7. 64 (dd, 1H), 7. 04 (dd, 1H), 6. 93-6. 82 (m, 2H), 6. 78 (m, 1H), 6. 66 (d, 1H), 4. 89 (m, 1H), 4. 05 (t, 2H), 3. 91 (m, 2H), 3. 44 (m, 2H), 2. 97 (t, 2H).  56 δ 8. 59 (d, 1H), 8. 45 (br s, 1H), 8. 40 (d, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 09-7. 02 (m, 2H), 6. 71 (m, 1H), 6. 66 (d, 1H), 6. 58 (m, 1H), 4. 89 (m, 1H), 3. 96 (t, 2H), 3. 92 (m, 2H), 3. 39 (m, 2H), 2. 95 (t, 2H).  57 δ 8. 87 (s, 1H), 8. 62 (d, 1H), 8. 33 (br s, 1H), 7. 78 (s, 1H), 7. 63 (d, 1H), 6. 97 (t, 2H), 6. 83 (m, 2H), 5. 36 (m, 1H), 3. 98 (t, 2H), 3. 91 (br t, 2H), 3. 43 (br s, 2H), 2. 95 (t, 2H).  58 δ 8. 88 (s, 1H), 8. 62 (d, 1H), 8. 29 (br s, 1H), 7. 77 (d, 1H), 7. 62 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 35 (m, 1H), 3. 99 (t, 2H), 3. 91 (m, 2H), 3. 42 (dd, 2H), 2. 95 (t, 2H).  59 δ 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 48 (br s, 1H), 7. 80 (s, 1H), 7. 64 (dd, 1H), 7. 38 (d, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 43 (m, 1H), 3. 98 (t, 2H), 3. 95 (m, 2H), 3. 42 (m, 2H), 2. 95 (t, 2H).  60 6 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 49 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 38 (d, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 43 (m, 1H), 3. 99 (t, 2H), 3. 95 (m, 2H), 3. 42 (m, 2H), 2. 95 (t, 2H).  179 δ 8. 65 (s, 1Η), 8. 59 (d, 1H), 8. 46 (br s, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 22 (m, 1H), 6. 74 (s, 1H), 6. 69-6. 64 (m, 2H), 6. 60 (dt, 1H), 4. 88 (m, 1H), 4. 01 (t, 2H), 3. 90 (m, 2H), 3. 40 (m, 2H), 2. 96 (t, 2H).  δ 8. 65 (s, 1H), 8. 59 (d, 1H), 8. 52 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 6. 92-6. 82 (m, 2H), 6. 78 (m, 1H), 6. 75 (s, 1H), 4. 88 (m, 1H), 4. 05 (t, 2H), 3. 90 (m, 2H), 3. 45 (m, 2H), 2. 97 (t, 2H).  δ 8. 65 (s, 1H), 8. 60 (d, 1H), 8. 45 (br s, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 7. 06 (m, 1H), 6. 74 (s, 1H), 6. 70 (m, 1H), 6. 58 (m, 1H), 4. 88 (m, 1H), 3. 96 (t, 2H), 3. 90 (m, 2H), 3. 39 (m, 2H), 2. 95 (t, 2H).  δ 8. 59 (d, 1H), 8. 45 (br s, 1H), 8. 40 (d, 1H), 7. 79 (d, 1H), 7. 63 (dd, 1H), 7. 19 (t, 1H), 7. 04 (d, 1H), 6. 94 (m, 1H), 6. 89 (t, 1H), 6. 78 (dd, 1H), 6. 66 (d, 1H), 4. 89 (m, 1H), 4. 01 (t, 2H), 3. 92 (m, 2H), 3. 40 (m, 2H), 2. 96 (t, 2H).  δ 8. 59 (d, 1H), 8. 46 (br s, 1H), 8. 40 (d, 1H), 8. 07 (d, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 52 (dd, 1H), 7. 04 (dd, 1H), 6. 71 (d, 1H), 6. 66 (d, 1H), 4. 88 (m, 1H), 4. 33 (t, 2H), 3. 90 (m, 2H), 3. 36 (m, 2H), 2. 95 (t, 2H).  δ 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 52 (br s, 1H), 7. 80 (s, 1H), 7. 65 (dd, 1H), 7. 38 (d, 1H), 7. 21 (m, 1H), 6. 70 - 6. 63 (m, 2H), 6. 61 (dt, 1H), 5. 43 (m, 1H), 4. 01 (t, 2H), 3. 94 (m, 2H), 3. 42 (m, 2H), 2. 96 (t, 2H).  δ 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 58 (br s, 1H), 7. 81 (s, 1H), 7. 66 (dd, 1H), 7. 38 (d, 1H), 6. 94-6. 82 (m, 2H), 6. 78 (m, 1H), 5. 44 (m, 1H), 4. 05 (t, 2H), 3. 94 (m, 2H), 3. 45 (m, 2H), 2. 97 (t, 2H).  δ 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 49 (br s, 1H), 7. 80 (s, 1H), 7. 65 (dd, 1H), 7. 38 (d, 1H), 7. 05 (m, 1H), 6. 71 (m, 1H), 6. 55 (m, 1H), 5. 43 (m, 1H), 3. 98-3. 92 (m, 4H), 3. 41 (m, 2H), 2. 95 (t, 2H).  δ 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 47 (br s, 1H), 8. 08 (d, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 52 (dd, 1H), 7. 38 (d, 1H), 6. 72 (d, 1H), 5. 42 (m, 1H), 4. 33 (t, 2H), 3. 94 (m, 2H), 3. 38 (m, 2H), 2. 94 (t, 2H).  5 8. 65 (s, 1H), 8. 60 (d, 1H), 8. 46 (br s, 1H), 8. 07 (d, 1H), 7. 77 (s, 1H), 7. 63 (d, 1H), 7. 52 (dd, 1H), 6. 74 (s, 1H), 6. 70 (d, 1H), 4. 87 (m, 1H), 4. 33 (t, 2H), 3. 88 (br t, 2H), 3. 37 (m, 2H), 2. 95 (t, 2H).  5 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 43 (br s, 1H), 7. 78 (s, 1H), 7. 62 (d, 1H), 7. 37 (d, 1H), 6. 95 (t, 2H), 6. 84 (m, 2H), 5. 40 (m, 1H), 4. 36 (m, 1H), 3. 94 (m, 2H), 3. 36 (m, 2H), 2. 78 (m, 2H), 1. 27 (d, 3H).  δ 8. 87 (s, 1H), 8. 61 (d, 1H), 8. 25 (br s, 1H), 7. 76 (s, 1H), 7. 61 (d, 1H), 6. 96 (t, 2H), 6. 84 (m, 2H), 5. 33 (m, 1H), 4. 35 (m, 1H), 3. 89 (m, 2H), 3. 36 (br m, 2H), 2. 77 (m, 2H), 1. 26 (d, 3H).  180 201204254 .  73 δ 8. 65 (d, 1Η), 8. 60 (d, 1H), 8. 36 (br s, 1H), 7. 78 (s, 1H), 7. 62 (dd, 1H), 7. 00 (d, 1H), 6. 96 (t, 2H), 6. 84 (m, 2H), 5. 36 (m, 1H), # 4. 35 (m, 1H), 3. 88 (m, 2H), 3. 38 (m, 2H), 2. 77 (ddd, 2H), 1. 26 * (d, 3H).  74 δ 8. 58 (d, 1H), 8. 51 (br s, 1H), 8. 41 (d, 1H), 7. 79 (d, 1H), 7. 64 (dd, 1H), 7. 13 (dd, 1H), 7. 04 (dd, 1H), 6. 92 (td, 1H), 6. 83 (dd, 1H), 6. 67 (d, 1H), 4. 88 (m, 1H), 4. 05 (t, 2H), 3. 96 (m, 2H), 3. 49 (m, 2H), 3. 00 (t, 2H).  75 δ 8. 58 (d, 1H), 8. 50 (br s, 1H), 8. 40 (d, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 10 (dd, 1H), 7. 04 (m, 2H), 6. 83 (t, 1H), 6. 66 (d, 1H), 4. 88 (m, 1H), 4. 06 (t, 2H), 3. 92 (m, 2H), 3. 44 (m, 2H), 2. 98 (t, 2H).  76 δ 8. 58 (d, 1H), 8. 50 (br s, 1H), 8. 41 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 37 (d, 1H), 7. 18 (dd, 1H), 7. 04 (dd, 1H), 6. 81 (d, 1H), 6. 67 (d, 1H), 4. 88 (m, 1H), 4. 06 (t, 2H), 3. 96 (m, 2H), 3. 49 (m, 2H), 3. 01 (t, 2H).  77 δ 8. 64 (s, 1H), 8. 59 (d, 1H), 8. 53 (br s, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 13 (dd, 1H), 6. 92 (td, 1H), 6. 83 (dd, 1H), 6. 75 (s, 1H), 4. 87 (m, 1H), 4. 04 (t, 2H), 3. 94 (m, 2H), 3. 50 (m, 2H), 3. 00 (t, 2H).  78 δ 8. 65 (s, 1H), 8. 59 (d, 1H), 8. 51 (br s, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 10 (dd, 1H), 7. 04 (m, 1H), 6. 86 (t, 1H), 6. 75 (s, 1H), 4. 87 (m, 1H), 4. 06 (t, 2H), 3. 90 (m, 2H), 3. 45 (m, 2H), 2. 98 (t, 2H).  79 δ 8. 65 (s, 1H), 8. 59 (d, 1H), 8. 52 (br s, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 37 (d, 1H), 7. 18 (dd, 1H), 6. 80 (d, 1H), 6. 75 (d, 1H), 4. 87 (m, 1H), 4. 06 (t, 2H), 3. 94 (m, 2H), 3. 49 (m, 2H), 3. 01 (t, 2H).  80 8. 88 (s, 1H), 8. 62 (d, 1H), 8. 28 (br s, 1H), 7. 77 (s, 1H), 7. 62 (d, 1H), 7. 37 (d, 2H), 6. 78 (d, 2H), 5. 35 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 42 (br s, 2H), 2. 95 (t, 2H).  81 8. 88 (s, 1H), 8. 62 (d, 1H), 8. 27 (br s, 1H), 7. 76 (s, 1H), 7. 62 (dd, 1H), 7. 28 (s, 4H), 6. 50 (dt, 1H), 6. 14 (dt, 1H), 5. 34 (m, 1H), 3. 83 (m, 2H), 3. 36-3. 31 (m, 4H).  82 8. 85 (s, 1H), 8. 62 (dd, 1H), 8. 25 (br s, 1H), 7. 76 (m, 1H), 7. 62 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 34 (m, 1H), 3. 83 (m, 2H), 3. 36-3. 31 (m, 4H).  83 8. 88 (d, 1H), 8. 61 (d, 1H), 8. 35 (br s, 1H), 7. 94 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 34 (m, 1H), 3. 83 (m, 2H), 3. 36-3. 31 (m, 4H).  84 8. 63-8. 58 (m, 2H), 8. 40 (br s, 1H), 7. 79 (m, 1H), 7. 74 (d, 1H), 7. 64 (dd, 1H), 7. 28 (s, 4H), 6. 50 (dt, 1H), 6. 15 (dt, 1H), 5. 33 (m, 1H), 3. 84 (m, 2H), 3. 35-3. 29 (m, 4H).  181 8. 71 (d, 1H), 8. 62 (d, 1H), 8. 31 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 33 (m, 1H), 3. 83 (m, 2H), 3. 33-3. 30 (m, 4H).  9. 00 (s, 1H), 8. 62 (d, 1H), 8. 23 (br s, 1H), 7. 76 (s, 1H), 7. 61 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 33 (m, 1H), 3. 83 (m, 2H), 3. 36-3. 30 (m, 4H).  8. 67 (d, 1H), 8. 62 (d, 1H), 8. 30 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 34 (m, 1H), 3. 84 (m, 2H), 3. 36-3. 31 (m, 4H).  8. 96 (s, 1H), 8. 62 (d, 1H), 8. 23 (br s, 1H), 7. 76 (s, 1H), 7. 62 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 33 (m, 1H), 3. 83 (m, 2H), 3. 36-3. 31 (m, 4H).  9. 05 (s, 1H), 8. 60 (d, 1H), 8. 30 (br s, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 42 (m, 1H), 3. 85 (m, 2H), 3. 37 (dd, 2H), 3. 34 (d, 2H).  8. 62 (d, 1H), 8. 39 (s, 1H), 7. 83 (s, 1H), 7. 70 (m, 2H), 7. 26 (s, 4H), 6. 47 (dt, 1H), 6. 11 (dt, 1H), 5. 36 (m, 1H), 3. 78 (m, 2H), 3. 29 (d, 2H), 3. 24 (m, 2H).  8. 90 (d, 1H), 8. 62 (d, 1H), 8. 20 (br s, 1H), 7. 77 (s, 1H), 7. 62 (d, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 29 (m, 1H), 3. 83 (m, 2H), 3. 38-3. 31 (m, 4H).  8. 65 (s, 1H), 8. 61 (d, 1H), 8. 49 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 58 (dd, 1H), 7. 16 (dd, 2H), 6. 75 (s, 1H), 6. 70 (m, 1H), 6. 58 (d, 1H), 4. 87 (m, 1H), 3. 82 (t, 2H), 3. 39 (m, 2H), 3. 36 (m, 2H).  8. 85 (d, 1H), 8. 64 (d, 1H), 8. 50 (br s, 1H), 8. 48 (d, 1H), 7. 80 (s, 1H), 7. 65 (dd, 1H), 7. 59 (dd, 1H), 7. 39 (d, 1H), 7. 24 (d, 1H), 6. 64 (m, 2H), 5. 43 (m, 1H), 3. 89 (t, 2H), 3. 39 (m, 2H), 3. 37 (m, 2H).  8. 85 (d, 1H), 8. 64 (d, 1H), 8. 46 (br s, 1H), 7. 80 (s, 1H), 7. 64 (dd, 1H), 7. 58 (dd, 1H), 7. 38 (d, 1H), 7. 17 (m, 2H), 6. 73 (m, 1H), 6. 60 (d, 2H), 5. 42 (m, 1H), 3. 91 (t, 2H), 3. 39 (m, 2H), 3. 37 (m, 2H).  8. 84 (d, 1H), 8. 59 (d, 1H), 8. 56 (s, 1H), 7. 97 (s, 1H), 7. 69 (d, 1H), 7. 38 (d, 1H), 7. 29 (m, 4H), 6. 52 (d, 1H), 6. 15 (dt, 1H), 5. 45 (m, 1H), 3. 88 (m, 2H), 3. 45 (m, 2H), 3. 37 (m, 2H).  8. 87 (d, 1H), 8. 47 (d, 1H), 8. 45 (s, 1H), 7. 61 (m, 1H), 7. 40 (m, 1H), 7. 38 (d, 1H), 7. 28 (m, 4H), 6. 50 (d, 1H), 6. 15 (dt, 1H), 5. 42 (m, 1H), 3. 87 (m, 2H), 3. 35-3. 31 (m, 4H).  8. 93 (s, 1H), 8. 89 (d, 1H), 8. 78 (s, 1H), 8. 71 (d, 1H), 7. 79 (d, 1H), 7. 37 (d, 1H), 7. 28 (m, 4H), 6. 49 (d, 1H), 6. 14 (dt, 1H), 5. 43 (m, 1H), 3. 86 (m, 2H), 3. 31 (m, 2H), 3. 27 (m, 2H).  s 182 201204254 100 8. 86 (d, 1H), 8. 61 (s, 1H), 8. 48 (d, 1H), 7. 61 (d, 1H), 7. 38 (d, 1H), 7. 27 (s, 4H), 6. 48 (d, 1H), 6. 13 (dt, 1H), 5. 43 (m, 1H), 3. 84 (m, 2H), 3. 30 (m, 2H), 3. 28 (m, 2H).  101 8. 99 (d, 1H), 8. 86 (d, 1H), 8. 58 (s, 1H), 8. 15 (s, 1H), 7. 93 (d, 1H), 7. 39 (d, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 14 (dt, 1H), 5. 44 (m, 1H), 3. 85 (m, 2H), 3. 45 (m, 2H), 3. 36-3. 31 (m, 4H).  102 9. 14 (d, 1H), 8. 88 (d, 1H), 8. 44 (d, 1H), 7. 96 (t, 1H), 7. 37 (d, 1H), 7. 29 (AB d, 4H), 6. 52 (d, 1H), 6. 17 (dt, 1H), 5. 43 (m, 1H), 3. 92 (m, 2H), 3. 34 (d, 2H), 3. 30 (m, 2H).  103 (major diastereomer only) 8. 85 (d, 1H), 8. 64 (s, 1H), 8. 61 (d, 1H), 7. 82 (s, 1H), 7. 67 (d, 1H), 7. 37 (d, 1H), 7. 28 (s, 4H), 6. 51 (d, 1H), 6. 17 (dt, 1H), 5. 54 (t, 1H), 3. 70 (t, 1H), 3. 62 (d, 1H), 3. 46-3. 38 (m, 2H), 3. 23 (dd, 1H), 1. 24 (d, 3H).  104 9. 70 (s, 1H), 8. 62 (d, 1H), 8. 42 (br s, 1H), 7. 81 (s, 1H), 7. 67 (d, 1H), 7. 28 (s, 4H), 6. 96 (s, 1H), 6. 51 (d, 1H), 6. 12 (dt, 1H), 5. 04 (m, 1H), 3. 87 (m, 2H), 3. 41 (m, 2H), 3. 36(d, 2H).  105 10. 45 (s, 1H), 9. 38 (d, 1H), 9. 08 (d, 1H), B. 93 (d, 1H), 8. 21 (dd, 1H), 7. 37 (d, 1H), 7. 29 (m, 4H), 6. 52 (d, 1H), 6. 18 (dt, 1H), 5. 42 (m, 1H), 3. 95 (m, 2H), 3. 37-3. 32 (m, 4H).  106 8. 61 (br s, 1H), 8. 59 (d, 1H), 8. 42 (d, 1H), 7. 81 (s, 1H), 7. 66 (d, 1H), 7. 27 (s, 4H), 6. 69 (d, 1H), 6. 50 (d, 1H), 6. 11 (dt, 1H), 4. 86 (m, 1H), 3. 78 (t, 2H), 3. 34 (br d, 4H).  107 8. 62-8. 56 (m, 2H), 8. 42 (d, 1H), 7. 80 (s, 1H), 7. 65 (d, 1H), 7. 27 (s, 4H), 6. 83 (d, 1H), 6. 49 (d, 1H), 6. 11 (dt, 1H), 4. 86 (m, 1H), 3. 77 (t, 2H), 3. 36-3. 29 (br d, 4H).  108 8. 73 (d, 1H), 8. 29 (br s, 1H), 8. 08 (s, 1H), 7. 35 (d, 1H), 7. 29 (m, 4H), 6. 52 (d, 1H), 6. 16 (dt, 1H), 5. 42 (m, 1H), 3. 87 (m, 2H), 3. 37-3. 27 (m, 4H).  109 8. 66 (d, 1H), 8. 62 (d, 1H), 8. 34 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 28 (s, 4H), 6. 48 (d, 1H), 6. 00 (dd, 1H), 5. 28 (m, 1H), 3. 80 (t, 1H), 3. 74 (t, 1H), 3. 29 (m, 2H), 3. 00 (m, 1H), 1. 16 (d, 3H).  110 8. 70 (d, 1H), 8. 62 (d, 1H), 8. 34 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 28 (s, 4H), 6. 48 (d, 1H), 6. 00 (dd, 1H), 5. 27 (m, 1H), 3. 80 (t, 1H), 3. 74 (t, 1H), 3. 30 (m, 2H), 3. 00 (m, 1H), 1. 16 (d, 3. H).  111 8. 65 (d, 1H), 8. 65 (s, 1H), 8. 52 (br s, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 13 (dt, 1H), 5. 54 (m, 1H), 3. 86 (dd, 2H), 3. 44 (m, 2H), 3. 34 (d, 2H).  112 8. 88 (d, 1H), 8. 61 (d, 1H), 8. 35 (br s, 1H), 7. 94 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 34 (m, 1H), 3. 98 (t, 2H), 3. 92 (m, 2H), 3. 40 (dd, 2H), 2. 95 (t, 2H).  1 13 8. 88 (d, 1H), 8. 61 (d, 1H), 8. 32 (br s, 1H), 7. 94 (d, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 91 (m, 2H), 3. 39 (m, 2H), 2. 95 (t, 2H).  183 201204254 114 8. 88 (d, 1H), 8. 61 (d, 1H), 8. 32 (br s, 1H), 7. 94 (d, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 36 (d, 2H), 6. 77 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 91 (m, 2H), 3. 39 (m, 2H), 2. 95 (t, 2H).  115 8. 88 (d, 1H), 8. 61 (d, 1H), 8. 37 (br s, 1H), 7. 95 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 6. 90 (td, 1H), 6. 85 (m, 1H), 6. 77 (m, 1H), 5. 34 (m, 1H), 4. 05 (t, 2H), 3. 92 (m, 2H), 3. 43 (dd, 2H), 2. 97 (t, 2H).  116 8. 66 (d, 1H), 8. 61 (d, 1H), 8. 39 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 01 (d, 1H), 6. 90 (td, 1H), 6. 85 (m, 1H), 6. 78 (m, 1H), 5. 38 (m, 1H), 4. 05 (t, 2H), 3. 92 (m, 2H), 3. 45 (dd, 2H), 2. 97 (t, 2H).  117 8. 67 (d, 1H), 8. 60 (d, 1H), 8. 38 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 13 (dd, 1H), 7. 01 (d, 1H), 6. 92 (m, 1H), 6. 84 (dd, 1H), 5. 38 (m, 1H), 4. 05 (t, 2H), 3. 97 (m, 2H), 3. 50 (dd, 2H), 3. 00 (t, 2H).  118 8. 67 (d, 1H), 8. 61 (d, 1H), 8. 37 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 10 (dd, 1H), 7. 04 (m, 1H), 7. 01 (d, 1H), 6. 87 (t, 1H), 5. 38 (m, 1H), 4. 05 (t, 2H), 3. 92 (m, 2H), 3. 45 (dd, 2H), 2. 97 (t, 2H).  119 8. 67 (d, 1H), 8. 61 (d, 1H), 8. 35 (br s, 1H), 7. 78 (d, 1H), 7. 63 (dd, 1H), 7. 37 (d, 1H), 7. 18 (dd, 1H), 7. 01 (d, 1H), 6. 82 (d, 1H), 5. 38 (m, 1H), 4. 07 (t, 2H), 3. 97 (m, 2H), 3. 49 (dd, 2H), 3. 00 (t, 2H).  120 8. 67 (d, 1H), 8. 61 (d, 1H), 8. 25 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 37 (d, 2H), 7. 01 (d, 1H), 6. 78 (d, 2H), 5. 37 (m, 1H), 3. 99 (t, 2H), 3. 93 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  121 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 48 (br s, 1H), 7. 79 (d, 1H), 7. 64 (dd, 1H), 7. 38 (d, 1H), 7. 36 (d, 1H), 7. 17 (dd, 1H), 6. 82 (d, 1H), 5. 42 (m, 1H), 4. 07 (t, 2H), 4. 01 (m, 2H), 3. 49 (dd, 2H), 3. 01 (t, 2H).  122 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 48 (br s, 1H), 7. 80 (s, 1H), 7. 64 (dd, 1H), 7. 38 (d, 1H), 7. 10 (dd, 1H), 7. 04 (m, 1H), 6. 88 (t, 1H), 5. 42 (m, 1H), 4. 07 (t, 2H), 3. 97 (m, 2H), 3. 44 (dd, 2H), 2. 98 (t, 2H).  123 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 48 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 38 (d, 1H), 7. 13 (dd, 1H), 6. 92 (m, 1H), 6. 84 (dd, 1H), 5. 42 (m, 1H), 4. 06 (t, 2H), 4. 01 (m, 2H), 3. 49 (dd, 2H), 3. 00 (t, 2H).  124 8. 76 (d, 1H), 8. 62 (d, 1H), 8. 38 (br s, 1H), 7. 85 (d, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 6. 90 (td, 1H), 6. 85 (m, 1H), 6. 78 (m, 1H), 5. 35 (m, 1H), 4. 05 (t, 2H), 3. 93 (m, 2H), 3. 43 (dd, 2H), 2. 97 (t, 2H).  125 8. 77 (d, 1H), 8. 62 (d, 1H), 8. 33 (br s, 1H), 7. 85 (d, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 37 (d, 2H), 6. 78 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 39 (br m, 2H), 2. 95 (t, 2H).  s 184 201204254 .  126 8. 77 (d, 1H), 8. 62 (d, 1H), 8. 33 (br s, 1H), 7. 85 (d, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 34 (m, 1H), .  3. 99 (t, 2H), 3. 92 (m, 2H), 3. 39 (br m, 2H), 2. 95 (t, 2H).  127 8. 88 (s, 1H), 8. 62 (d, 1H), 8. 35 (br s, 1H), 7. 78 (s, 1H), 7. 63 (d, 1H), 6. 90 (td, 1H), 6. 85 (m, 1H), 6. 78 (m, 1H), 5. 36 (m, 1H), 4. 05 (t, 2H), 3. 92 (m, 2H), 3. 46 (m, 2H), 2. 97 (t, 2H).  128 8. 63-8. 58 (m, 2H), 8. 41 (br s, 1H), 7. 79 (m, 1H), 7. 75 (d, 1H), 7. 63 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 34 (m, 1H), 3. 92 (t, 2H), 3. 92 (m, 2H), 3. 39 (m, 2H), 2. 96 (t, 2H).  129 8. 98 (d, 1H), 8. 63 (m, 1H), 8. 53 (br s, 1H), 8. 19 (m, 1H), 7. 80 (m, 1H), 7. 66 (m, 1H), 6. 92 (td, 1H), 6. 86 (m, 1H), 6. 78 (m, 1H), 5. 45 (m, 1H), 4. 06 (t, 2H), 3. 94 (m, 2H), 3. 47 (dd, 2H), 2. 98 (t, 2H).  130 8. 98 (d, 1H), 8. 63 (dd, 1H), 8. 45 (br s, 1H), 8. 19 (m, 1H), 7. 79 (dd, 1H), 7. 64 (dd, 1H), 7. 37 (d, 2H), 6. 78 (d, 2H), 5. 43 (m, 1H), 4. 00 (t, 2H), 3. 94 (m, 2H), 3. 43 (m, 2H), 2. 96 (t, 2H).  131 8. 98 (d, 1H), 8. 63 (dd, 1H), 8. 45 (br s, 1H), 8. 19 (m, 1H), 7. 79 (dd, 1H), 7. 64 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 43 (m, 1H), 4. 00 (t, 2H), 3. 94 (m, 2H), 3. 43 (m, 2H), 2. 96 (t, 2H).  132 8. 98 (d, 1H), 8. 63 (dd, 1H), 8. 47 (br s, 1H), 8. 19 (m, 1H), 7. 79 (dd, 1H), 7. 65 (dd, 1H), 6. 97 (t, 2H), 6. 83 (m, 2H), 5. 44 (m, 1H), 3. 99 (t, 2H), 3. 94 (m, 2H), 3. 44 (dd, 2H), 2. 96 (t, 2H).  133 8. 87 (d, 1H), 8. 61 (d, 1H), 8. 34 (br s, 1H), 7. 93 (d, 1H), 7. 77 (br s, 1H), 7. 62 (dd, 1H), 6. 96 (t, 2H), 6. 84 (m, 2H), 5. 31 (m, 1H), 4. 36 (m, 1H), 3. 88 (m, 2H), 3. 35 (m, 2H), 2. 77 (ddd, 2H), 1. 26 (d, 3H).  134 8. 76 (d, 1H), 8. 61 (dd, 1H), 8. 35 (br s, 1H), 7. 84 (d, 1H), 7. 77 (dd, 1H), 7. 62 (dd, 1H), 6. 96 (t, 2H), 6. 84 (m, 2H), 5. 31 (m, 1H), 4. 36 (m, 1H), 3. 88 (m, 2H), 3. 35 (m, 2H), 2. 77 (ddd, 2H), 1. 26 (d, 3H).  135 8. 63-8. 57 (m, 2H), 8. 40 (br s, 1H), 7. 78 (m, 1H), 7. 74 (d, 1H), 7. 62 (dd, 1H), 6. 96 (t, 2H), 6. 84 (m, 2H), 5. 31 (m, 1H), 4. 36 (m, 1H), 3. 89 (m, 2H), 3. 34 (m, 2H), 2. 78 (ddd, 2H), 1. 26 (d, 3H).  136 8. 97 (d, 1H), 8. 62 (d, 1H), 8. 45 (br s, 1H), 8. 18 (m, 1H), 7. 78 (dd, 1H), 7. 63 (dd, 1H), 6. 96 (t, 2H), 6. 84 (m, 2H), 5. 41 (m, 1H), 4. 37 (m, 1H), 3. 91 (m, 2H), 3. 38 (m, 2H), 2. 78 (ddd, 2H), 1. 26 (d, 3H).  137 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 51 (br s, 1H), 7. 80 (s, 1H), 7. 64 (m, 1H), 7. 38 (d, 1H), 6. 83 (s, 4H), 5. 43 (m, 1H), 3. 98 (t, 2H), 3. 94 (m, 2H), 3. 76 (s, 3H), 3. 42 (m, 2H), 2. 94 (t, 2H).  138 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 44 (br s, 1H), 8. 20 (d, 2H), 7. 78 (s, 1H), 7. 64 (dd, 1H), 7. 39 (d, 1H), 6. 96 (d, 2H), 5. 43 (m, 1H), 4. 12 (t, 2H), 3. 99 (m, 2H), 3. 43 (m, 2H), 3. 01 (t, 2H).  185 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 47 (br s,1H), 7. 79 (s, 1H), 7. 64 (m, 1H), 7. 38 (d, 1H), 7. 14 (d, 2H), 6. 88 (d, 2H), 5. 43 (m, 1H), 4. 01 (t, 2H), 3. 96 (m, 2H), 3. 42 (m, 2H), 2. 96 (t, 2H).  8. 85 (d, 1H), 8. 63 (d, 1H), 8. 45 (br s, 1H), 7. 79 (s, 1H), 7. 65 (m, 1H), 7. 59 (d, 2H), 7. 39 (d, 1H), 6. 95 (d, 2H), 5. 42 (m, 1H), 4. 07 (t, 2H), 3. 97 (m, 2H), 3. 42 (m, 2H), 2. 99 (t, 2H).  8. 84 (d, 1H), 8. 63 (d, 1H), 8. 52 (br s, 1H), 7. 81 (s, 1H), 7. 65 (m, 1H), 7. 38 (d, 1H), 7. 29 (d, 2H), 6. 84 (d, 2H), 5. 43 (m, 1H), 4. 01 (t, 2H), 3. 93 (m, 2H), 3. 43 (m, 2H), 2. 95 (t, 2H), 1. 29 (s, 9H).  8. 85 (d, 1H), 8. 63 (d, 1H), 8. 46 (br s, 1H), 7. 79 (s, 1H), 7. 64 (m, 1H), 7. 54 (d, 2H), 7. 39 (d, 1H), 6. 96 (d, 2H), 5. 43 (m, 1H), 4. 07 (t, 2H), 3. 97 (m, 2H), 3. 43 (br s, 2H), 2. 99 (t, 2H).  8. 76 (d, 1H), 8. 61 (d, 1H), 8. 30 (br s, 1H), 7. 84 (d, 1H), 7. 76 (s, 1H), 7. 61 (dd, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 30 (m, 1H), 4. 40 (m, 1H), 3. 89 (m, 2H), 3. 33 (ddd, 2H), 2. 77 (ddd, 2H), 1. 27 (d, 3H).  8. 62 (d, 1H), 8. 39 (s, 1H), 7. 83 (s, 1H), 7. 74 (br s, 1H), 7. 71 (dd, 1H), 6. 95 (t, 2H), 6. 81 (m, 2H), 5. 37 (m, 1H), 3. 95 (t, 2H), 3. 86 (m, 2H), 3. 32 (m, 2H), 2. 91 (t, 2H).  8. 62 (d, 1H), 8. 39 (s, 1H), 7. 83 (s, 1H), 7. 74 (br s, 1H), 7. 70 (dd, 1H), 7. 21 (d, 2H), 6. 80 (d, 2H), 5. 36 (m, 1H), 3. 96 (t, 2H), 3. 86 (m, 2H), 3. 31 (m, 2H), 2. 91 (t, 2H).  8. 62 (d, 1H), 8. 39 (s, 1H), 7. 83 (s, 1H), 7. 70 (dd, 1H), 7. 67 (br s, 1H), 7. 35 (d, 2H), 6. 75 (d, 2H), 5. 36 (m, 1H), 3. 95 (t, 2H), 3. 86 (m, 2H), 3. 30 (m, 2H), 2. 91 (t, 2H).  8. 70 (d, 1H), 8. 62 (d, 1H), 8. 30 (br s, 1H), 7. 76 (s, 1H), 7. 61 (dd, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 31 (m, 1H), 4. 40 (m, 1H), 3. 88 (m, 2H), 3. 34 (ddd, 2H), 2. 77 (ddd, 2H), 1. 27 (d, 3H).  8. 62 (d, 1H), 8. 38 (s, 1H), 7. 82 (s, 1H), 7. 69 (dd, 1H), 7. 75-7. 60 (br s, 1H), 7. 20 (d, 2H), 6. 80 (d, 2H), 5. 32 (m, 1H), 4. 37 (m, 1H), 3. 82 (m, 2H), 3. 26 (ddd, 2H), 2. 74 (ddd, 2H), 1. 24 (d, 3H).  8. 99 (s, 1H), 8. 62 (d, 1H), 8. 24 (br s, 1H), 7. 75 (s, 1H), 7. 60 (dd, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 31 (m, 1H), 4. 40 (m, 1H), 3. 88 (m, 2H), 3. 35 (ddd, 2H), 2. 77 (ddd, 2H), 1. 27 (d, 3H).  8. 99 (s, 1H), 8. 62 (d, 1H), 8. 27 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 35 (m, 1H), 3. 98 (t, 2H), 3. 92 (m, 2H), 3. 43 (m, 2H), 2. 95 (t, 2H).  8. 99 (s, 1H), 8. 62 (d, 1H), 8. 28 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 91 (m, 2H), 3. 43 (m, 2H), 2. 95 (t, 2H).  8. 99 (s, 1H), 8. 62 (d, 1H), 8. 27 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 37 (d, 2H), 6. 77 (d, 2H), 5. 35 (m, 1H), 3. 99 (t, 2H), 3. 91 (m, 2H), 3. 42 (m, 2H), 2. 95 (t, 2H).  s 186 201204254 .  153 8. 71 (d, 1H), 8. 62 (d, 1H), 8. 33 (br s, 1H), 7. 78 (s, 1H), 7. 63 (d, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 35 (m, 1H), 4. 00 (t, 2H), 3. 92 ^ (m, 2H), 3. 42 (br m, 2H), 2. 95 (t, 2H).  154 8. 71 (d, 1H), 8. 62 (d, 1H), 8. 33 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 37 (d, 2H), 6. 78 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 41 (m, 2H), 2. 95 (t, 2H).  155 8. 71 (d, 1H), 8. 62 (d, 1H), 8. 35 (br s, 1H), 7. 78 (s, 1H), 7. 63 (dd, 1H), 6. 97 (t, 2H), 6. 83 (m, 2H), 5. 35 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 43 (m, 2H), 2. 95 (t, 2H).  156 8. 66 (d, 1H), 8. 62 (d, 1H), 8. 29 (br s, 1H), 7. 76 (d, 1H), 7. 61 (dd, 1H), 7. 37 (d, 2H), 6. 78 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  157 8. 66 (d, 1H), 8. 62 (d, 1H), 8. 31 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 35 (m, 1H), 3. 99 (t, 2H), 3. 93 (m, 2H), 3. 41 (m, 2H), 2. 95 (t, 2H).  158 8. 66 (d, 1H), 8. 62 (d, 1H), 8. 31 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 6. 97 (t, 2H), 6. 83 (m, 2H), 5. 35 (m, 1H), 3. 98 (t, 2H), 3. 93 (m, 2H), 3. 41 (m, 2H), 2. 95 (t, 2H).  159 8. 95 (s, 1H), 8. 61 (d, 1H), 8. 21 (br s, 1H), 7. 75 (s, 1H), 7. 60 (dd, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 31 (m, 1H), 4. 40 (m, 1H), 3. 89 (ddd, 2H), 3. 35 (ddd, 2H), 2. 77 (ddd, 2H), 1. 27 (d, 3H).  160 9. 03 (s, 1H), 8. 62 (d, 1H), 8. 27 (br s, 1H), 7. 76 (s, 1H), 7. 62 (dd, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 40 (m, 1H), 4. 41 (m, 1H), 3. 91 (m, 2H), 3. 38 (ddd, 2H), 2. 78 (m, 2H), 1. 27 (d, 3H).  161 8. 84 (s, 1H), 8. 62 (d, 1H), 8. 23 (br s, 1H), 7. 75 (s, 1H), 7. 60 (d, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 32 (m, 1H), 4. 40 (m, 1H), 3. 89 (m, 2H), 3. 35 (m, 2H), 2. 77 (m, 2H), 1. 27 (d, 3H).  162 8. 66 (d, 1H), 8. 62 (d, 1H), 8. 28 (br s, 1H), 7. 76 (s, 1H), 7. 61 (dd, 1H), 7. 22 (d, 2H), 6. 82 (d, 2H), 5. 31 (m, 1H), 4. 40 (m, 1H), 3. 89 (m, 2H), 3. 34 (ddd, 2H), 2. 78 (ddd, 2H), 1. 27 (d, 3H).  163 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 40 (br s, 1H), 7. 77 (s, 1H), 7. 61 (dd, 1H), 7. 37 (d, 1H), 7. 21 (d, 2H), 6. 84 (d, 2H), 5. 37 (m, 1H), 4. 21 (m, 1H), 3. 94 (t, 1H), 3. 88 (t, 1H), 3. 33 (dd, 1H), 3. 28 (dd, 1H), 2. 78 (m, 2H), 1. 68 (m, 2H), 0. 95 (t, 3H).  164 8. 96 (s, 1H), 8. 62 (d, 1H), 8. 22 (br s, 1H), 7. 75 (s, 1H), 7. 61 (dd, 1H), 7. 37 (d, 2H), 6. 78 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  165 8. 96 (s, 1H), 8. 62 (d, 1H), 8. 21 (br s, 1H), 7. 75 (s, 1H), 7. 61 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 34 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 40 (dd, 2H), 2. 94 (t, 2H).  166 8. 96 (s, 1H), 8. 62 (d, 1H), 8. 22 (br s, 1H), 7. 75 (s, 1H), 7. 61 (dd, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 34 (m, 1H), 3. 98 (t, 2H), 3. 92 (m, 2H), 3. 41 (m, 2H), 2. 94 (t, 2H).  187 8. 85 (s, 1H), 8. 62 (dd, 1H), 8. 23 (br s, 1H), 7. 76 (m, 1H), 7. 61 (dd, 1H), 7. 37 (d, 2H), 6. 78 (d, 2H), 5. 35 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  8. 85 (s, 1H), 8. 62 (dd, 1H), 8. 24 (br s, 1H), 7. 76 (m, 1H), 7. 61 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 35 (m, 1H), 3. 99 (t, 2H), 3. 92 (m, 2H), 3. 41 (m, 2H), 2. 95 (t, 2H).  8. 85 (s, 1H), 8. 62 (d, 1H), 8. 25 (br s, 1H), 7. 76 (m, 1H), 7. 62 (dd, 1H), 6. 97 (t, 2H), 6. 83 (m, 2H), 5. 35 (m, 1H), 3. 98 (t, 2H), 3. 92 (m, 2H), 3. 41 (m, 2H), 2. 95 (t, 2H).  9. 04 (s, 1H), 8. 63 (d, 1H), 8. 28 (br s, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 43 (m, 1H), 4. 00 (t, 2H), 3. 94 (m, 2H), 3. 44 (m, 2H), 2. 96 (t, 2H).  8. 62 (s, 1H), 8. 59 (d, 1H), 8. 46 (br s, 1H), 8. 06(d, 1H), 7. 76 (s, 1H), 7. 62 (dd, 1H), 7. 50 (dd, 1H), 6. 72 (s, 1H), 6. 65 (d, 1H), 5. 23 (m, 1H), 4. 83 (m, 1H), 3. 84 (m, 2H), 3. 36 (dd, 1H), 3. 29 (dd, 1H), 2. 84 (dd, 1H), 2. 74 (dd, 1H), 1. 29 (d, 3H).  8. 84 (d, 1H), 8. 63 (d, 1H), 8. 48 (br s, 1H), 8. 07 (d, 1H), 7. 79 (s, 1H), 7. 64 (d, 1H), 7. 50 (dd, 1H), 7. 37 (d, 1H), 6. 65 (d, 1H), 5. 39 (m, 1H), 5. 24 (m, 1H), 3. 91 (m, 2H), 3. 36 (dd, 1H), 3. 30 (dd, 1H), 2. 84 (dd, 1H), 2. 74 (dd, 1H), 1. 30 (d, 3H).  8. 65 (s, 1H), 8. 61 (d, 1H), 8. 40 (br s, 1H), 8. 05 (d, 1H), 7. 76 (s, 1H), 7. 62 (dd, 1H), 7. 37 (d, 1H), 7. 10 (dd, 1H), 6. 73 (s, 1H), 4. 88 (m, 1H), 4. 04 (m, 2H), 3. 92 (m, 2H), 3. 41 (m, 2H), 2. 98 (dd, 2H).  8. 84 (d, 1H), 8. 63 (d, 1H), 8. 48 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 38 (d, 1H), 7. 36 (d, 1H), 6. 99 (d, 1H), 5. 43 (m, 1H), 4. 55 (dd, 2H), 3. 96 (m, 2H), 3. 39 (m, 2H), 3. 03 (dd, 2H).  8. 64 (s, 1H), 8. 60 (d, 1H), 8. 42 (br s, 1H), 8. 05 (d, 1H), 7. 76 (s, 1H), 7. 62 (dd, 1H), 7. 23 (d, 1H), 7. 18 (dd, 1H), 6. 73 (s, 1H), 4. 88 (m, 1H), 4. 05 (m, 2H), 3. 92 (m, 2H), 3. 40 (m, 2H), 2. 98 (dd, 2H).  8. 64 (s, 1H), 8. 60 (d, 1H), 8. 43 (br s, 1H), 7. 77 (s, 1H), 7. 63 (dd, 1H), 7. 37 (d, 1H), 6. 98 (d, 1H), 6. 73 (s, 1H), 4. 88 (m, 1H), 4. 55 (m, 2H), 3. 92 (m, 2H), 3. 38 (m, 2H), 3. 02 (dd, 2H).  8. 85 (d, 1H), 8. 63 (d, 1H), 8. 44 (br s, 1H), 8. 05 (d, 1H), 7. 78 (s, 1H), 7. 64 (dd, 1H), 7. 39 (d, 1H), 7. 21 (m, 2H), 5. 42 (m, 1H), 4. 05 (dd, 2H), 3. 96 (m, 2H), 3. 41 (m, 2H), 2. 98 (dd, 2H).  8. 85 (d, 1H), 8. 63 (d, 1H), 8. 45 (br s, 1H), 8. 05 (d, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 38 (m, 2H), 7. 11 (dd, 1H), 5. 42 (m, 1H), 4. 05 (dd, 2H), 3. 98 (m, 2H), 3. 43 (m, 2H), 2. 98 (dd, 2H).  8. 84 (d, 1H), 8. 63 (dd, 1H), 8. 39 (br s, 1H), 7. 77 (dd, 1H), 7. 61 (dd, 1H), 7. 37 (d, 1H), 7. 22 (m, 2H), 6. 82 (m, 2H), 5. 38 (m, 1H), 4. 40 (m, 1H), 3. 96 (m, 1H), 3. 91 (m, 1H), 3. 36 (m, 1H), 3. 22 (m, 1H), 2. 80 (dd, 1H), 2. 75 (dd, 1H), 1. 28 (d, 3H).  s 188 201204254 .  180 8. 89 (d, 1H), 8. 61 (d, 1H), 8. 16 (br s, 1H), 7. 75 (s, 1H), 7. 60 (dd, 1H), 7. 22 (m, 2H), 6. 82 (m, 2H), 5. 26 (m, 1H), 4. 40 (m, 1H), _ 3. 90 (m, 1H), 3. 86 (m, 1H), 3. 37 (m, 1H), 3. 33 (m, 1H), 2. 79 (dd, 1H), 2. 74 (dd, 1H), 1. 27 (d, 3H).  181 8. 89 (d, 1H), 8. 61 (d, 1H), 8. 23 (br s, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 23 (d, 2H), 6. 82 (d, 2H), 5. 30 (m, 1H), 3. 99 (t, 2H), 3. 90 (m, 2H), 3. 42 (m, 2H), 2. 94 (t, 2H).  182 8. 65 (s, 1H), 8. 61 (d, 1H), 8. 44 (br s, 1H), 8. 16 (s, 1H), 7. 77 (s, 1H), 7. 63 (m, 2H), 6. 74 (s, 1H), 6. 66 (d, 1H), 4. 87 (m, 1H), 4. 33 (m, 2H), 3. 89 (m, 2H), 3. 37 (m, 2H), 2. 95 (dd, 2H).  183 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 47 (br s, 1H), 8. 17( s, 1H), 7. 80 (s, 1H), 7. 64 (m, 2H), 7. 38 (d, 1H), 6. 69 (d, 1H), 5. 42 (m, 1H), 4. 34 (t, 2H), 3. 94 (m, 2H), 3. 38 (m, 2H), 2. 94 (t, 2H) 184 8. 64 (s, 1H), 8. 61 (d, 1H), 8. 41 (br s, 1H), 8. 19 (d, 1H), 7. 76 (s, 1H), 7. 63 (dd, 1H), 6. 82 (d, 1H) 6. 74 (m, 2H), 4. 88 (m, 1H), 4. 07 (dd, 2H), 3. 92 (m, 2H), 3. 39 (m, 2H), 2. 98 (dd, 2H).  185 8. 85 (d, 1H), 8. 63 (d, 1H), 8. 43 (br s, 1H), 8. 19 (d, 1H), 7. 78 (s, 1H), 7. 64 (dd, 1H), 7. 39 (d, 1H), 6. 84 (dd, 1H), 6. 75 (dd, 1H), 5. 42 (m, 1H), 4. 07 (dd, 2H), 3. 97 (m, 2H), 3. 40 (m, 2H), 2. 98 (dd, 2H).  186 8. 59 (m, 3H), 8. 44 (s, 2H), 7. 78 (s, 1H), 7. 64 (dd, 1H), 6. 72 (s, 1H), 4. 86 (m, 1H), 4. 41 (t, 2H), 3. 87 (m, 2H), 3. 43 (m, 2H), 2. 97 (t, 2H).  187 8. 83 (d, 1H), 8. 63 (d, 1H), 8. 56 (br s, 1H), 8. 44 (s, 2H), 7. 80 (s, 1H), 7. 64 (dd, 1H), 7. 36 (d, 1H), 5. 42 (m, 1H), 4. 40 (t, 2H), 3. 93 (m, 2H), 3. 42 (m, 2H), 2. 97 (t, 2H).  188 8. 65 (d, 1H), 8. 52 (s, 1H), 8. 48 (br s, 1H), 7. 76 (s, 1H), 7. 61 (dd, 1H), 7. 21 (m, 2H), 6. 81 (m, 2H), 5. 51 (m, 1H), 4. 41 (m, 1H), 3. 95 (m, 1H), 3. 90 (m, 1H), 3. 46 (m, 1H), 3. 42 (m, 1H), 2. 81 (dd, 1H), 2. 77 (dd, 1H), 1. 27 (d, 3H).  189 8. 83 (d, 1H), 8. 61 (d, 1H), 8. 39 (s, 1H), 7. 93 (s, 1H), 7. 65 (dd, 1H), 7. 37 (d, 1H), 7. 22 (m, 2H), 6. 82 (m, 2H), 5. 38 (m, 1H), 4. 40 (m, 1H), 3. 95 (m, 1H), 3. 91 (m, 1H), 3. 37 (m, 1H), 3. 32 (m, 1H), 2. 80 (dd, 1H), 2. 75 (dd, 1H), 1. 28 (d, 3H).  190 8. 84 (d, 1H), 8. 61 (d, 1H), 8. 41 (s, 1H), 7. 94 (s, 1H), 7. 66 (dd, 1H), 7. 38 (d, 1H), 7. 23 (m, 2H), 6. 82 (d, 2H), 5. 42 (m, 1H), 3. 99 (t, 2H), 3. 96 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  191 8. 84 (d, 1H), 8. 61 (d, 1H), 8. 42 (s, 1H), 7. 94 (s, 1H), 7. 66 (d, 1H), 7. 38 (d, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 42 (m, 1H), 4. 00-3. 94 (m, 4H), 3. 41 (m, 2H), 2. 95 (t, 2H).  192 8. 86 (d, 1H), 8. 46 (d, 1H), 8. 43 (s, 1H), 7. 59 (m, 1H), 7. 40 (s, 1H), 7. 38 (d, 1H), 7. 22 (m, 2H), 6. 82 (m, 2H), 5. 39 (m, 1H), 4. 40 (m, 1H), 3. 95 (m, 1H), 3. 91 (m, 1H), 3. 36 (m, 1H), 3. 32 (m, 1H), 2. 80 (dd, 1H), 2. 75 (dd, 1H), 1. 28 (d, 3H).  189 201204254 193 8. 87 (d, 1H), 8. 47 (d, 1H), 8. 43 (s, 1H), 7. 60 (m, 1H), 7. 40 (s, 1H), 7. 38 (d, 1H), 7. 23 (m, 2H), 6. 82 (d, 2H), 5. 42 (m, 1H), 3. 99 (t, 2H), 3. 97 (m, 2H), 3. 40 (m, 2H), 2. 95 (t, 2H).  194 8. 87 (d, 1H), 8. 47 (d, 1H), 8. 44 (s, 1H), 7. 61 (m, 1H), 7. 40 (m, 1H), 7. 38 (d, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 42 (m, 1H), 4. 00- 3. 95 (m, 4H), 3. 40 (m, 2H), 2. 95 (t, 2H).  195 8. 91 (s, 1H), 8. 88 (d, 1H), 8. 77 (s, 1H), 8. 70 (d, 1H), 7. 79 (d, 1H), 7. 37 (d, 1H), 7. 21 (m, 2H), 6. 82 (m, 2H), 5. 40 (m, 1H), 4. 39 (m, 1H), 3. 93 (m, 1H), 3. 89 (m, 1H), 3. 30 (m, 1H), 3. 26 (m, 1H), 2. 78 (dd, 1H), 2. 73 (dd, 1H), 1. 27 (d, 3H).  196 8. 85 (d, 1H), 8. 58 (s, 1H), 8. 48 (d, 1H), 7. 60 (d, 1H), 7. 37 (d, 1H), 7. 21 (m, 2H), 6. 81 (m, 2H), 5. 39 (m, 1H), 4. 38 (m, 1H), 3. 92 (m, 1H), 3. 87 (m, 1H), 3. 31 (m, 1H), 3. 27 (m, 1H), 2. 78 (dd, 1H), 2. 72 (dd, 1H), 1. 27 (d, 3H).  197 8. 86 (d, 1H), 8. 58 (s, 1H), 8. 48 (d, 1H), 7. 60 (d, 1H), 7. 38 (d, 1H), 7. 22 (m, 2H), 6. 81 (d, 2H), 5. 42 (m, 1H), 3. 97 (t, 2H), 3. 93 (m, 2H), 3. 34 (m, 2H), 2. 92 (t, 2H).  198 8. 86 (d, 1H), 8. 58 (s, 1H), 8. 48 (d, 1H), 7. 61 (d, 1H), 7. 38 (d, 1H), 6. 96 (t, 2H), 6. 82 (m, 2H), 5. 43 (m, 1H), 3. 96 (t, 2H), 3. 93 (m, 2H), 3. 35 (m, 2H), 2. 92 (t, 2H).  199 8. 90 (s, 1H), 8. 89 (d, 1H), 8. 78 (s, 1H), 8. 70 (d, 1H), 7. 79 (d, 1H), 7. 38 (d, 1H), 6. 96 (t, 2H), 6. 83 (m, 2H), 5. 43 (m, 1H), 3. 98-3. 94 (m, 4H), 3. 33 (m, 2H), 2. 92 (t, 2H).  200 8. 90 (s, 1H), 8. 89 (d, 1H), 8. 78 (s, 1H), 8. 70 (d, 1H), 7. 79 (d, 1H), 7. 38 (d, 1H), 7. 22 (m, 2H), 6. 82 (d, 2H), 5. 43 (m, 1H), 4. 00- 3. 93 (m, 4H), 3. 33 (m, 2H), 2. 93 (t, 2H).  201 8. 98 (d, 1H), 8. 85 (d, 1H), 8. 53 (s, 1H), 8. 14 (s, 1H), 7. 91 (d, 1H), 7. 39 (d, 1H), 7. 22 (m, 2H), 6. 82 (m, 2H), 5. 40 (m, 1H), 4. 40 (m, 1H), 3. 94 (m, 1H), 3. 90 (m, 1H), 3. 37 (m, 1H), 3. 33 (m, 1H), 2. 80 (dd, 1H), 2. 75 (dd, 1H), 1. 28 (d, 3H).  202 9. 12 (d, 1H), 8. 86 (d, 1H), 8. 43 (d, 1H), 7. 96 (t, 1H), 7. 36 (d, 1H), 7. 22 (m, 2H), 6. 84 (m, 2H), 5. 40 (m, 1H), 4. 41 (m, 1H), 3. 98 (m, 1H), 3. 94 (m, 1H), 3. 33 (m, 1H), 3. 29 (m, 1H), 2. 82 (dd, 1H), 2. 76 (dd, 1H), 1. 29 (d, 3H).  203 10. 29 (s, 1H), 8. 95 (d, 1H), 8. 86 (d, 1H), 8. 14 (d, 1H), 7. 36 (d, 1H), 7. 22 (m, 2H), 6. 84 (m, 2H), 5. 40 (m, 1H), 4. 42 (m, 1H), 4. 03-3. 94 (m, 2H), 3. 41-3. 33 (m, 2H), 2. 86-2. 74 (m, 2H), 1. 30 (d, 3H).  204 9. 13 (br d, 1H), 8. 87 (d, 1H), 8. 44 (d, 1H), 7. 96 (t, 1H), 7. 38 (d, 1H), 7. 23 (m, 2H), 6. 84 (d, 2H), 5. 43 (m, 1H), 4. 04-3. 98 (m, 4H), 3. 36 (m, 2H), 2. 97 (t, 2H).  201204254 .  205 9. 70 (s, 1H), 8. 62 (d, 1H), 8. 35 (br s, 1H), 7. 79 (s, 1H), 7. 64 (dd, 1H), 7. 22 (m, 2H), 6. 95 (s, 1Ή), 6. 82 (m, 2H), 5. 00 (m, 1H), 4. 42 .  (m, 1H), 3. 94 (t, 1H), 3. 90 (t, 1H), 3. 44 (dd, 1H), 3. 40 (dd, 1H), 2. 83-2. 77 (m, 2H), 1. 27 (d, 3H).  206 10. 42 (s, 1H), 9. 38 (d, 1H), 9. 08 (d, 1H), 8. 92 (d, 1H), 8. 21 (dd, 1H), 7. 36 (d, 1H), 7. 22 (m, 2H), 6. 85 (m, 2H), 5. 39 (m, 1H), 4. 41 (m, 1H), 4. 00 (m, 2H), 3. 38 (dd, 1H), 3. 34 (dd, 1H), 2. 83 (dd, 1H), 2. 77 (dd, 1H), 1. 29 (d, 3H).  207 10. 44 (s, 1H), 9. 38 (d, 1H), 9. 08 (d, 1H), 8. 93 (d, 1H), 8. 21 (dd, 1H), 7. 37 (d, 1H), 7. 23 (m, 2H), 6. 84 (d, 2H), 5. 43 (m, 1H), 4. 04 (m, 2H), 4. 01 (t, 2H), 3. 41 (m, 2H), 2. 98 (t, 2H).  208 8. 65 (s, 1H), 8. 61 (d, 1H), 8. 45 (br s, 1H), 7. 95 (d,lH), 7. 77 (s, 1H), 7. 63 (d, 1H), 7. 33 (m, 1H), 6. 74 (s, 1H), 6. 72 (dd, 1H), 4. 87 (m, 1H), 4. 32 (t, 2H), 3. 89 (m, 2H), 3. 36 (m, 2H), 2. 95 (t, 2H).  209 8. 85 (d, 1H), 8. 62 (d, 1H), 8. 45 (br s, 1H), 7. 95 (d, 1H), 7. 79 (s, 1H), 7. 63 (d, 1H), 7. 38 (m, 1H), 7. 33 (m, 1H), 6. 73 (dd, 1H), 5. 42 (m, 1H), 4. 32 (t, 2H), 3. 94 (m, 2H), 3. 39 (m, 2H), 2. 94 (t, 2H).  210 8. 59 (d, 1H), 8. 52 (br s, 1H), 8. 42 (d, 1H), 7. 77 (s, 1H), 7. 62 (dd, 1H), 7. 21 (m, 2H), 6. 80 (m, 2H), 6. 66 (d, 1H), 4. 82 (m, 1H), 4. 39 (m, 1H), 3. 85 (m, 2H), 3. 37 (dd, 1H), 3. 32 (dd, 1H), 2. 82- 2. 74 (m, 2H), 1. 26 (d, 3H).  211 8. 59 (d, 1H), 8. 51 (br s, 1H), 8. 41 (d, 1H), 7. 77 (s, 1H), 7. 61 (dd, 1H), 7. 21 (m, 2H), 6. 80 (m, 3H), 6. 66 (d, 1H), 4. 82 (m, 1H), 4. 39 (m, 1H), 3. 85 (m, 2H), 3. 36 (dd, 1H), 3. 31 (dd, 1H), 2. 82- 2. 74 (m, 2H), 1. 26 (d, 3H).  212 8. 65 (d, 1H), 8. 64 (s, 1H), 8. 50 (br s, 1H), 7. 76 (s, 1H), 7. 61 (dd, 1H), 7. 21 (m, 2H), 6. 81 (m, 2H), 5. 50 (m, 1H), 4. 41 (m, 1H), 3. 94 (m, 1H), 3. 88 (m, 1H), 3. 44 (m, 2H), 2. 84-2. 74 (m, 2H), 1. 27 (d, 3H).  213 9. 39 (br s, 1H), 8. 59 (d, 1H), 8. 48 (s, 1H), 7. 87 (s, 1H), 7. 72 (d, 1H), 7. 49 (d, 1H), 7. 40 (dd, 1H), 7. 27 (d, 2H), 7. 22 (d, 2H), 6. 40 (d, 1H), 6. 00 (dt, 1H), 3. 81 (m, 1H), 3. 58 (m, 2H), 3. 21-3. 12 (m, 4H).  214 8. 58 (s, 1H), 7. 91 (s, 1H), 7. 85 (d, 1H), 7. 76 (d, 1H), 7. 27 (s, 4H), 7. 06 (d, 1H), 6. 48 (d, 1H), 6. 09 (dt, 1H), 5. 85 (br s, 1H), 4. 65 (m, 1H), 3. 70 (m, 2H), 3. 29(d, 2H), 3. 22 (m, 2H).  215 8. 28 (d, 1H), 7. 55 (d, 1H), 7. 36 (s, 1H), 7. 29 (m, 4H), 7. 25 (d, 1H), 7. 03 (d, 1H), 6. 51 (d, 1H), 6. 14 (dt, 1H), 5. 21 (m, 1H), 3. 83 (m, 2H), 3. 39 (s, 3H), 3. 30 (m, 2H), 3. 2-2. 8 (br m, 2H).  216 8. 61 (d, 1H), 8. 49 (br s, 1H), 8. 15 (s, 1H), 7. 80 (s, 1H), 7. 66 (dd, 1H), 7. 28 (s, 4H), 6. 50 (d, 1H), 6. 13 (dt, 1H), 5. 38 (m, 1H), 3. 82 (m, 2H), 3. 38-3. 31(m, 4H).  191 201204254 217 8. 61 (d, 1H), 8. 45 (br s,1H), 8. 06 (s, 1H), 7. 79 (s, 1H), 7. 65 (dd, 1H), 7. 28 (s, 4H), 6. 49 (d, 1H), 6. 13 (dt, 1H), 5. 37 (m, 1H), 3. 81 (m, 2H), 3. 36-3. 30 (m, 4H).  218 8. 61 (d, 1H), 8. 32 (br s, 1H), 7. 76 (s, 1H), 7. 63 (dd, 1H), 7. 27 (s, 4H), 6. 49 (d, 1H), 6. 12 (dt, 1H), 5. 34 (m, 1H), 3. 81 (m, 2H), 3. 31(m, 4H).  219 8. 85 (d, 1H), 8. 64 (d, 1H), 8. 40 (br s, 1H), 7. 79 (s, 1H), 7. 63 (d, 1H), 7. 39 (d, 1H), 7. 12 (d, 2H), 6. 54 (d, 2H), 5. 40 (m, 1H), 3. 91 (t, 2H), 3. 27 (br s, 2H), 3. 09 (br m, 2H), 2. 81 (br m, 2H).  220 8. 26 (d, 1H), 7. 53 (d, 1H), 7. 34 (s, 1H), 7. 25 (d, 1H), 7. 22 (m, 2H), 7. 02 (d, 1H), 6. 83 (m, 2H), 5. 18 (m, 1H), 4. 39 (m, 1H), 3. 87 (m, 2H), 3. 39 (s, 3H), 3. 3-2. 8 (m, 2H), 2. 77 (dd, 1H), 2. 72 (dd, 1H), 1. 28 (d, 3H).  221 8. 85 (d, 1H), 8. 64 (d, 1H), 8. 40 (br s, 1H), 7. 78 (s, 1H), 7. 62 (dd, 1H), 7. 38 (d, 1H), 7. 16 (d, 2H), 6. 62 (d, 2H), 5. 39 (m, 1H), 3. 88 (m, 2H), 3. 34 (t, 2H), 3. 28 (m, 2H), 2. 93 (s, 3H), 2. 74 (t, 2H).  222 8. 27 (d, 1H), 7. 54 (d, 1H), 7. 35 (s, 1H), 7. 25 (d, 1H), 7. 23 (m, 2H), 7. 03 (d, 1H), 6. 83 (m, 2H), 5. 21 (m, 1H), 3. 98 (t, 2H), 3. 92 (t, 2H), 3. 39 (s, 3H), 3. 3-2. 8 (br m, 2H), 2. 92 (t, 2H).  223 8. 60 (d, 1H), 8. 48 (br s, 1H), 8. 14 (s, 1H), 7. 79 (s, 1H), 7. 65 (d, 1H), 7. 22 (m, 2H), 6. 82 (m, 2H), 5. 36 (m, 1H), 4. 41 (m, 1H), 3. 89 (t, 1H), 3. 84 (t, 1H), 3. 44-3. 33 (br m, 2H), 2. 83-2. 73 (m, 21H), 1. 26 (d, 3H).  224 8. 60 (d, 1H), 8. 40 (br s, 1H), 7. 75 (s, 1H), 7. 62 (dd, 1H), 7. 21 (m, 2H), 6. 80 (m, 2H), 5. 30 (m, 1H), 4. 39 (m, 1H), 3. 85 (m, 2H), 3. 36 (m, 1H), 3. 31 (m, 1H), 2. 79 (dd, 1H), 2. 73 (m, 1H), 1. 26 (d, 3H).  225 9. 32 (br s, 1H), 8. 81 (d, 1H), 8. 59 (d, 1H), 7. 83 (s, 1H), 7. 69 (d, 1H), 7. 35 (d, 1H), 7. 26 (obscured, 2H), 7. 19 (d, 2H), 6. 43 (d, 1H), 6. 12 (m, 1H), 5. 42 (m, 1H), 3. 16 (d, 2H), 2. 71 (m, 2H), 2. 47 (m, 1H), 1. 92 (m, 2H), 1. 74 (m, 1H), 1. 26 (m, 2H).  226 8. 84 (d, 1H), 8. 63 (d, 1H), 8. 51 (s, 1H), 7. 76 (s, 1H), 7. 62 (d, 1H), 7. 35 (d, 1H), 7. 30 (AB d, 4H), 6. 52 (d, 1H), 6. 30 (m, 1H), 5. 35 (m, 1H), 3. 25 (br s, 2H), 2. 88 (br s, 2H), 2. 51 (br s, 2H), 2. 21 (br s, 2H), 1. 98 (br s, 2H).  227 8. 82 (d, 1H), 8. 74 (br s, 1H), 8. 59 (d, 1H), 7. 80 (s, 1H), 7. 65 (d, 1H), 7. 36 (d, 1H), 7. 28 (s, 4H), 6. 52 (d, 1H), 6. 27 (m, 1H), 5. 64 (m, 1H), 3. 32 (m, 2H), 3. 10 (m, 2H), 2. 80 (m, 1H), 2. 52 (m, 1H), 2. 42 (m, 1H), 2. 08 (m, 1H).  s 192 201204254 a H NMR data is a low field ppni deviating from tetradecyl decane. Couplings are indicated as (s)_single peak, (4)-doublet, (1)-trimodal, (m)_multimodal, (dd)-doublet, (dt)-double triplet, (td)-triplet, (br s) · wide single peak, (br t) - wide three peaks.

Biological Example of the Invention Test A In order to measure the control of Plutella xylostella, the test unit contained a small open shell and a radish that grew for 12 to 14 days. This test unit was pre-infested with approximately 50 newborn larvae, which were distributed to the test unit via a corn bristle using a bazooka inoculator. After being dispensed into the test unit, the larva moves to the test plant. Use a solution containing 10% acetone, 90% water and 300 ppm X·778 containing aryl (aryl polyoxyethylene, free fatty acids, glycols and isopropanol)

Spreader Lo-Foam Formula Nonionic surfactant (Loveland Industries, Inc. Greeley, Colorado, USA) formulated test compounds. Above the top of each test unit at 1.27 cm (0.5 inch), through the SUJ2 nebulizer nozzle with 1/8 JJ custom body (Spraying

Systems Co. Wheaton, Illinois, USA) Apply 1 mL of the formulated compound liquid. Test compound 250 and / or 50 ppm was sprayed and repeated three times. After spraying the prepared compound, each test unit was allowed to dry for 1 hour, and then a black shield cap was placed on top of it. The test unit was held in the growth chamber for 6 days at 25 C and 70% relative humidity. Plant feeding damage was then visually assessed based on leaf loss. In the tests of the compounds of formula 1 tested, the following compounds provided very good to optimal control efficacy at 250 ppm or lower 193 201204254 plant damage and/or 100%% mortality): Compounds 1, 2, 3 , 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 19, 20, 23, 24, 25, 26, 28, 29, 30, 31, 35 , 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 50, 51, 5 52, 53, 54, 55, 57, 58, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 77, 78, 79, 80, 82, 83, 84, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135 and 214. 10 In the test of the compound of formula 1 tested, the following compounds provided extremely good to optimal control efficacy at 50 ppm (40% or less plant damage and/or 100%% mortality): Compounds 1, 2 , 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 16, 17, 20, 21, 22, 23, 25, 26, 29, 31, 35, 38, 40, 43 , 45, 47, 15 48, 50, 51, 52, 55, 57, 58, 59, 60, 61, 62, 63, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 78, 80, 81, 82, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 95, 96, 97, 98, 99, 101, 103, 104, 106, 107, 109, 110, 11 112, 113, 114, 116, 117, 118, 119, 120, 2, 12, 122, 123, 124, 125, 126, 127, 128, 129, 130, m, 132, 133, 134, 135, 136, 138, 139, 140, 143, 144, 145, 146, 147, 149, 150, 15 152, 153, 154, 155, 156, 157, 158, 160, 16 162, 163, 164, 165, 166, 167, 168, 169, 170, 172, 173, 174, 175, 176, 25 177, 179, 180, 18 182, 183, 189, 190, 19 2,

S 194 201204254 193, 194, 201, 205, 208, 209, 213, 214, 215, 217, 218, 219, 220, 221, 222, 223, 224, 226 and 227.

Test B 5 In order to evaluate the control of the autumn army worm (Spodoptera frugiperda), the test unit consisted of a small open shell of 4 to 5 day old corn (maize) plants. This test unit was pre-infested with 10-15 day old larvae on an insect bait (using a core sampler). Test compounds were formulated as described in Test A and sprayed at 250 and/or 50 ίο PPm. The above administration was repeated three times. After spraying, the test unit was maintained in a 25 ° C and 70% relative humidity growth chamber and then visually evaluated as described in Test a. In the test of the compound of formula 1 tested, the following compounds provided extremely good to optimal control efficacy at 250 ppm (plant damage and/or 100% mortality at 4% or less): Compounds 1, 2 , 3, 8, 9, 10, 12, 13, 14, 16, 17, 20, 23, 24, 25, 26, 50, 51, 52, 57, 58, 65, 66, 67, 68, 69, 70 , 71, 72, 73, 77, 78, 79, 80, 82, 83, 84, 112, 113, 114, 115, 117, 118, 119, 120, 12, 122, 123, 125, 126, 2〇127 , 129, 130, 131, 132, 133 and 134. In the tests of the compounds of formula 1 tested, the following compounds provided extremely good to optimal control efficacy at 5 〇ppm (plant damage and/or 100% mortality at 40% or less): Compounds 2, 3 , 4, 5, 6, 7, 8, 9, 10, 12, 13, 14, 16, 17, 20, 2, 22, 25, 23, 25, 26, 3, 52, 57, 58, 59, 60, 66, 68, 69, 7 Bu 72, 73, 8 Bu 82, 84, 85, 86, 87, 88, 89, 90, 195 201204254 5 91, 92, 94, 95 ' 96 ' 97 ' 98, 99, 100 101' 102, 103, 104, 106, 107, 109, 110, 111, 112, 113, 114, 115, 118, 119, 120, 121, 122, 123, 127, 130, 131, 136, 137, 139 , 143, 146, 147, 150, 15 152, 153, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 172, 178 , 179, 180, 18 183, 189, 190, 19 192, 193, 2 (Π, 205, 209, 210, 215, 216, 217, 219, 220, 221, 222, 223, 224, 226 and 227 10

Test C 15 20 In order to evaluate the control of Myzus persicae via contact and/or systemic means, the test unit consisted of a small open shell with 12 to 15 day old radish plants inside. This was pre-infested by placing 3G-4G prawn on the leaves cut from the cultured plants on the leaves of the test plants (cutting method). When the leaves are dry, the insects move to the test plant. After pre-infestation, the soil of the test unit is covered with sand. Test compounds were formulated as described in Test A and sprayed at 25 〇 and/or 5 〇 PPm. The above administration was repeated three times. Sprinkle the prepared compound in the mouth 2 ' County test material Lin 1 hour, then the - black shield $ Yu Qiqing. The test was carried out for 6 days in the growth chamber at 19% of the heart 5 (MQ% phase). The Kunming mortality of each test unit was then visually evaluated. In the test of the 41 compound tested, the following 25 pawn formation into at least 8G% mortality: compound 丨, 6, 7, 丨 14, 16, 17, 20, 2, 22, 23, 24, 25, 40, 45, 47,

S 196 25 201204254 48, 50, 51, 52, 53, 57, 58, 59, 60, 61, 63, 66, 67, 68, 69, 70, 71, 72, 73, 79, 80, 85, 86, 88, 91, 94, 95, 97, 98, 103, 106, 107, 109, 110, 112, 113, 114, 116, 118, 119, 120, 12, 122, 123, 124, 125, 126, 127, 129, 130, m, 132, 133, 134, 135, 136, 137, 143, 144, 145, 147, 149, 150, 15 152, 153, 155, 158, 160, 162, 163, 165, 166, 167, 168, 169, 170, m, 172, 174, 178, 179, 180, 18 182, 183, 189, 190, 19 192, 194, 195, 2 (U, 205, 210, 219, 221 and 227. In the test of the compound of formula 1 tested, the following caused at least 80% mortality at 50 ppm: Compound 11, 16, 17, 25, 40, 45, 50, 5, 52, 58, 59, 60, 66 , 67, 68, 69, 70, 7 Bu 72, 85, 9 Bu 103, 112, 114, 116, 119, 120, 121, 122, 123, 124, 125, 127, 130, 13 Bu 132, 133, 134 , 137, 147, 150, 152, 153, 155, 158, 168, 170, 179, 181 and 183.

Test D 20 In order to evaluate the control of Frankliniella occidentalis via contact and/or systemic means, the test unit consisted of a small open shell with a 5-7 day old sun bean plant inside. Test compounds were formulated and sprayed at 250 and/or 50 ppm as described in Test A and repeated three times. After spraying, the test unit has a drying time of 1 hour and 25 hours, after which 22 to 27 mature flowers are placed in the test unit ¢. 197 201204254 and blackened; The test unit was kept in a growth chamber at 25 ° C and a relative humidity of 45-55% for 7 days. In the test of the compound of formula 1 tested, the following compounds provided extremely good to optimal control efficacy at 25 〇ppm (plant damage and/or 1 (8)% mortality at 3% or less): Compound 1, 16, 17, 60, 69, 71, 85, 90, 91, 94, 95, 96, 97, 98, 101, 103, 109, 110, m, 130, 131, 147, 162, 163, 172, 174, 177, 179, 181, 183, 187, 189, 190, 191, 192, 193, 2 (Π, 209, 215, 220, 222, 224, and 227 〇10 In the test of the compound of formula 1 tested, the following compounds were Very good to optimal control efficacy at 50 ppm (30% or less plant damage and/or 100% mortality): Compounds 1 and 94.

Test E 15 In order to evaluate the control of potato leaf mites (Empoasca fabae) via contact and/or systemic means, the test unit consists of a small open shell with 5 to 6 day old Soleil bean plants (with nascent leaves) composition. Test compounds were formulated and sprayed at 250 and/or 50 2 〇 ppm as described in Test A and repeated three times. After the spray, the test unit was allowed to dry for 1 hour and then infested with 5 potato leafhoppers (18 to 21 day old adults). The black sieve cover is placed on the cylinder. The test unit was held in the growth chamber for 6 days at 24 ° C and 70% relative humidity. The insect mortality of each test unit was then visually assessed.

S 198 201204254 In the test of the compound of formula 1 tested, the following caused at least 80% mortality at 250 ppm: compounds 71, 72, u〇, 136, 159, 163, 172, 179, 180 and 201. In the test of the compound of formula 1 tested below, at 50 ppm, 5 caused at least 80% mortality: compound 163 °

Test F In order to evaluate the control of Aphis gossypii via contact and/or system, the test unit consisted of a small open shell with a 6 to 7 day old cotton plant inside. This was pre-infested by 30-40 insects on one leaf according to the cutting method described in Test C, and the soil of the test unit was covered with a layer of sand. The test compound was formulated as described in Test A and sprayed at 250 ppm and repeated three times. After spraying, the test unit was maintained in a chamber of 19 to 21 ° C and 50 to 70% relative humidity growth chamber, and then visually evaluated as described in Test C. In the test of the compound of formula 1 tested, the following caused at least 80% mortality at 250 ppm: Compound 5.

Test G 20 To evaluate the control of corn borer (Peregrinus maidis) via contact and/or systemology, the test unit consisted of a small open shell with 3 to 4 day old corn ears inside. Add white sand to the top of the soil. Test compounds were formulated and sprinkled at 250 ppm as described in Test A and repeated three times. After spraying, the test unit was allowed to dry for 1 hour, and then subsequently infested with 15 to 20 nymphs (18 to 21 days old). The black sieve cover is placed on the cylinder. The 199 201204254 test unit was maintained in the growth chamber for 6 days at 24 ° C and 70% relative humidity. The insect mortality of each test unit was then visually assessed. In the test of the compound of formula 1 tested, the following caused at least 80% mortality at 250 ppm: Compounds 85 and 132. 5 In addition to tests A to G, tests for the evaluation of the control of the root nodule nematode (eloidogyne incognita) were also carried out, but no significant activity against this additional non-vertebrate pest was observed under the test frequency of the test. Οο [Simple diagram description] [Main component symbol description]

Claims (1)

201204254 ‘ VII. Patent application scope: . 1 · A compound selected from formula 1, an N oxide thereof or a salt thereof, , c / L - R6 r / V where 10 A1 is N or CR7; A2 is N or CR8; A3 is N or CR9; A4 is N or CR10; and the constraints are A1, A2, A3 and A4 τ system , s(0)k or NR36; no more than two systems N; 15 L-C (R&gt;C (R^ and R&quot; bonded carbon atoms are also bonded to CR R5' and R! 2 bonded carbon atoms are also bonded to the ulnar 6; or optionally 4 or 4 diphenyl groups independently selected from R 1 ; substituents; 4-C (R34) (R35 )_z_, wherein the carbon atom established with R34 and R35! is also bonded to CW and Z is bonded to R6; Z is 0, S(0)m, NR37 or CR38r39; R1 is - selectively up to 5 phenyl or 5- or 6-membered heteroaromatic rings independently substituted with a substituent selected from R14; 201 20 R2 hydrazine, hydroxy, Cl-C6 alkyl, Cr_c6 haloalkyl, c2_c6 alkenyl, C2-c6 Alkenyl, c2-c6 alkynyl, c3-c6 haloalkynyl, C3-C7 cycloalkyl, C4-C8 cycloalkyl, c-c7 cycloalkenyl, Q-C6 alkoxy, qq alkoxy Alkyl, -CHO, CCW^R15 . C(0)0R16, C(〇)NR17R18 ^ S(0)pR19 or s(o)2nr2Gr21 ; each R3 is independently halogen, cyano, Ci-C4 Alkyl or C-C4 alkoxy; R4 is hydrazine or Q-C4 alkyl; R5 is hydrazine or Ci-c4 alkyl; R6 is optionally substituted with up to 5 substituents independently selected from R22 Phenyl or 5- or 6-membered heteroaromatic ring; R, R, R9 and R10 are independently H, _, Ni, nitro, 〇R23, NW, c-C6 alkyl, Ci-C6 (tetra), C2-C6 dilute group, c2-c6 _ group, c2_c6 block group, C3_C6 tooth fast group, C3-c7 cycloalkyl group, c4-c8 cycloalkylalkyl group, C5_C7 cycloalkenyl group, -CHO, C(W2)R26 , c(〇)〇r27, c(〇)nr28r29, S(9)qR30, S(0)2Nr28r29 or 〇c(〇)r31: or a benzene optionally substituted with up to 5 substituents independently selected from R4. Phenyl or 5- or 6-membered heteroaryl ring; or one and r8 8 and ^, or the adjacent couple of R9 and f, and their even pairs (four) connected with the stone anti-atoms - formed - copper or 5 members or 6 members a cyclic or non-aromatic ring comprising a ring member selected from the group consisting of carbon atoms and up to 3 heteroatoms independently selected from L 0 and S; R 11 and R 12 are independently H, halogen, c Γ - ganodioxy; Cl~C2, or Ci-ca, R13, R14, R22 and R4G are independently halogen, cyano, nitro, OR23, NR24R 25, C rQ alkyl, C rC6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C3-C6 haloalkynyl, C3-C7 cycloalkyl, C4-C8 ring Alkylalkyl, C5-C7 cycloalkenyl, -CHO, C(W2)R26, C(0)0R27, C(0)NR28R29, S(0)qR30, S(0)2NR28R29 or 0C(0)R31 R15 and R16 are independently CrQ alkyl, Cr-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C3-C6 haloalkynyl, C3-C7 cycloalkyl , C4-C8 cycloalkylalkyl or C5-C7 cycloalkenyl; or optionally up to 3 independently selected from _, cyano, nitro, OR23, NR24R25, QQ alkyl, C2-C4 alkenyl , C2-C4 alkynyl, CrQ haloalkyl, C2-C6 alkoxyalkyl, c2-c4 haloalkenyl, -CHO, C(W2)R26, C(0)0R27, c(o)nr28r29, S (0) a phenyl group substituted with a substituent of qR3°, s(o)2nr28r29 and 〇C(0)R31; each of R17 and R20 is independently Η, Q-C6 alkyl, CrQ haloalkyl, C2-C6 Alkenyl, c2-c6 haloalkenyl, c2-C6 alkynyl, C3-C6 haloalkynyl, C3-C:7 cycloalkyl, c4-c8 cycloalkylalkyl or c5-c7 cycloalkenyl; or selected Up to 3 independently selected from the group consisting of halogen, cyano, nitro, OR23, NR24R25, c-c4 , C2-C4 alkenyl, &lt;:2-(:4 fast radical, Ci-Cj i!alkyl, c2_c6 methoxyoxyalkyl, C2-C4 haloalkenyl, _ch〇, C(W2)R26, C (0) 0R27, C (〇) NR28R29, S(〇) qR3. , S(〇)2NR28R29 and the substituent of 0C(0)R are substituted. Alkenyl or c2-c6 alkynyl; 201204254 Each Rl9, R26, r27 and R30 are independently c "c6 炫 or c" C6 haloalkyl; each R2/ and R31 is independently H, Cl-C6 alkyl or C plant c6-dentate; each R25, R36 and R37 is independently H, Ci_C6 alkyl, c(0)R32 or C (〇)〇R33 ; each R28 and R32 are independently H, C widely c6 alkyl, C wide c6 haloalkyl, cr~C6 alkenyl, c2-C6 _ dilute, c2_C6 fast radical, c3-C6 4 Base, Cr~C7 cycloalkyl, c4-C8 cycloalkylalkyl or C5-C7 cycloalkenyl; 10 each R is independently CH: 6 alkyl, Cl_c6 haloalkyl, C2_C6 dilute, C2-C6 halo Alkenyl, c2-c6 alkynyl, c3-c6 haloalkynyl, C3~C7 cycloalkyl, Q-Cs cycloalkylalkyl or c5-C7 cycloalkenyl; 15 R H, Cl-C4 alkyl, Ci-c2 i hospital base, c2-c4 dilute group, CfC4 alkynyl group, c丨-c4 alkoxy group or cyano group; R35 system hydrazine or methyl group; ί =, 0 Η, dentate, C1-C2 炫 or C1 - C2 alkoxy; is selected from the group consisting of H, cyano and C-C2 alkyl, and when it is a sensation, the R 9 is additionally selected from halogen; or ',, 20 R, R39 and R above The carbon atom to which 38 and R39 are attached - represents a carbonyl moiety, and each of the W2 systems is independently 0 or s; k is 0, 1 or 2; 25 201204254 n is an integer from 〇 to 5; Ρ 0, 丨Or 2; each q series is independently 〇, 1 2; S series 1, 2 or 3; and t is 1 or 2; the limiting condition is the sum of s and t, 2, 3 or 4. 2. The compound according to Item 1, wherein: T is 〇; Z is 〇; R is a 4 ° 咬 base ring substituted with 1 to 3 substituents independently selected from R 14 wherein one of the substituents is located The second position of the 4-% mouth base ring (2-position); R2 system Η, fluorenyl group, Cr_C5 alkoxyalkyl group or Cr_C4 alkoxycarbonyl group; R system hydrazine or alkyl group; R5 system Η; R6 system selection Optionally having up to 5 phenyl rings independently substituted with a substituent selected from R22 or optionally substituted with up to 4 substituents independently selected from R22; R7, R8, R9 and R10 are independently Is hydrazine, halogen, Cr*C4 alkyl, Ci-Q haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 alkynyl, C3-C4 haloalkynyl, c3-c6 cycloalkyl , ch: 4 alkoxy, Cr·Q haloalkoxy, Cl—c4 alkylthio, Cl_c4 haloalkylthio Or a cyano group, or R7 and r8, or R8 and R9, or an adjacent couple of R9 and R10, together with the carbon atom to which they are attached, form a 5- or 6-membered aromatic non-aromatic ring comprising a carbon selected from carbon Original 205 201204254 and up to 3 ring members independently selected from the hetero atom of ruthenium, osmium and S; R, R12 are independently H, halogen or methyl; each R13 is halogen or methyl; each R14 is independent , Ci_C4, Ke C4, Cyan, C2-C4, C2-C4 i alkenyl, c2-c4, K3-C4, alkoxy, Qj-C: 6-cycloalkyl , Cl-C4 alkoxy, Cl-c4 halogen alkoxy, Ci-C4 alkylthio or Cr-Q haloalkylthio; each R22 is independently halogen, cyano, C "C6 alkyl, Cl-c6 Halogenated C3-C6 cycloalkyl, c2-C6 dilute, C2-C6 haloalkenyl, Cr~C6 alkynyl, Q-C6 alkoxy or Cr~C6 halo alkoxy; R34 hydrazine or Cl- C2 alkyl; R35 system; 15 W system; η system 〇; s system 1; and t system; as described in claim 2, wherein: A1 is N or CR7; A2 is N or CR8; A3 is N or CR9; A4 is CR10; L system, -C(R34)(R35)〇- or unsubstituted extension 201204254 R1 is a 4-pyridine ring substituted with a substituent selected from R14, wherein the above substituent is located at the second position of the 4-pyridine ring (2-position); R2 system Η; 5 R4 system Η or methyl; R6 is a benzene ring substituted with 1 to 3 substituents independently selected from r22 or a pyridine ring' wherein one of the substituents is in the para position; R, R, R and R are independently Η , halogen or C1-C4 halogen compound; R11 and R12 system Η; ίο each R14 is independently halogen or Cr~C4 haloalkyl; each R22 is independently F, a, Br, cyano, CH3, CF3, ring Propyl, HOC, CH30 or CF3 oxime; and R34 oxime or methyl. The compound according to claim 3, wherein: R6 is a benzene ring or a pyridine ring which is substituted in the para position with a substituent independently selected from R22 and is optionally independently selected from the ortho position. Substituted by a substituent of R22; R7 is hydrazine or F; 20 R8 and R9 are independently hydrazine, halogen or Ci-Q i alkyl; R1Q is hydrazine or F; each R14 is independently F, a, Br or; Each R22 is independently F, a, Br, CF3 or Cf3〇. The compound of claim 4, wherein: r6 is a benzene ring substituted in the para position with a substituent selected from R22; 207 201204254 R7 system; R8 system Η, halogen or CF3; R9 system Η , halogen or CF3; R10 system Η; 5 R14 system Cl; and R22 system F, α, Br or CF3. 6. The compound of claim 1 which is selected from the group consisting of 2-chloro-indole-[2-[[1-[(2Ε)-3-(4-chlorophenyl)-) 2-propen-1-yl]-3-吖ίο丁α定基]oxy]-6-(disorder methyl)-3-α ratio α-based]-4-σΗ^ bite Wei 酉 basket amine, 2_ chlorine -Ν-[4,5-Dichloro-2-[[1-[(2Ε)_3-(4-chlorophenyl)-2-propenyl)-yl]-3-azetidinyl]oxy]phenyl -4-Acridine Carboxamide, 2-Chloro-N-[6-Gas-2-[[1-[(2Ε)-3-(4-chlorophenyl)-2-propen-1-yl) ]·3-α丫丁 π定基]oxy]-5·gas-3-° ratio π定基]-4-° than biting weiganamine, 2-chloro-Ν-[5-gas-2-[[ 1-[(2Ε)-3-(4-Phenylphenyl)-2-propen-1-yl]-3-α丫丁α定基]oxy]-6-rat-3-° ratio α-based]- 4-α ratio α-determination of western basket amine, 20 2-chloro·Ν·[2-[[1-[(2Ε)·3-(4-chlorophenyl)·2·propylene·1_yl)-2 - Mercapto-3-azetidinyl]oxy]-6-(trifluoromethyl)-3-. Bipyridyl-4-pyridinium carboxamide, and 2-chloro-N-[6-chloro-2-[[l-[2-(4-chlorophenoxy)propyl]-3-azetidinyl ] oxy]-5-fluoro-3-° ratio °]-4-4b carboxy guanamine. S 208 201204254 7. The compound according to claim 5, which is 2-gas-Ν-[2-[[1-[(2Ε)-3-(4-chlorophenyl)-2-propenyl]_3 - azetidinyl]oxy]-6-(trifluoromethyl)_3_pyridyl&gt; 4-pyridinecarboxamide. 5. A composition comprising the compound of claim 1 and at least one additional component selected from the group consisting of a surfactant, a solid diluent, and a liquid diluent, the composition optionally further comprising At least one additional bioactive compound or agent. 9. The composition of claim 8, wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acephate, acequinocyl, subculture (acetamiprid), acetoprole, acrinathrin, amidoflumet, amitraz, avermectin, azadirachtin, valsin ( Azinphos-methyl ), bifenthrin, bifenazate, bistrifluron, borate, buprofezin, carbaryl, carbofuran ), cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl , chromafenozide, clofentezin, clothianidin, cyantraniliprole, cyflumetofen, cyfluthrin, beta Beta-cyfluthrin, cyhalothrin' gamma-cyhalothrin, λ 赛洛宁 201204254 (lambda-cyhalothrin), cypermethrin, alpha-cypermethrin ), zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dieldrin, 5 phoenix (diflubenzuron), dimefluthrin, dimehypo, dimethoate, dinotefuran, diofenolan, emamectin, ampoules Endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenothiocarb, Fenoxycarb, fenpropathrin, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, · Mildewamine 15 ( flufenerim ) Flufenoxuron, fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide , hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isfenfens ), lufenuron, malathion, mepyrfluthrin, metaflumizone, metaldehyde, methamidophos, methidathion, annihilation Methiodicarb, methomyl, metoprene, methoxy DDT 201204254 ' (methoxychlor), metofluthrin, sulphate, monocrotophos, methoxyfenozide , nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, armor Parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, Profenofos, profluthrin, propargite, protrifenbute, pymetrozine, pyraflupr〇ie, pyrethrin ), pyripaben, pyridalyl, pyrifluquinazon, pyriprole, pyriproxyfen, rotenone, ryan 〇dine ), spinetoram, spinosad, spirodiclofen, spiromesifeil, spirotetramat, sUlfoxaflor , sulprofos, tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, insecticidal 2〇 Tetrachlorvinphos) Rin), tetramethylfluthrin, thiadopHd, thiamethoxam, thiodicarb, thiosultap-sodium, tefife Yrad ), tralomethrin, t»triazamate, tricholson rfon, triflumuron, Bacillus thuringiensis, entomopathogenic bacteria (ent〇in〇pathogenic 211 201204254 bacteria), a group consisting of all strains of Nucleo polyhydrosis viruses, entomopathogenic viruses, and entomopathogenic fungi. 10. The composition of claim 9, wherein the at least one additional biologically active compound or agent is selected from the group consisting of abamectin, acetamiprid, acrinthrin, and amitraz. ), avermectin, azadirachtin, bifenthrin, buprofezin, carbaryl, cartap, chlorantraniliprole, kefan Chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, λ Lamma-cyhalothrin gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-Cypermethrin, cyromazine , deltamethrin, dieldrin, dinotefuran, diofenolan, emamectin, end〇Sulfan, esfenvalerate ), Ethiprole, etofenprox, etoxazole, fenothiocarb, fenoxycarb, fenvalerate, fipronii, fluoride Fluonicamid, flubendiamide, flufenoxuron, fluvalinate, formetanate, hexaflumuron, hydramethylnon, edaamine 201204254 r ( imidacloprid ), indoxacarb, lufenur〇n, mepyrfluthrin, metaflumizone, methiodicarb, methodyl ,methoprene, meth〇xyfenozide, nitenpyram, nithiazine, novaiuron, oxarnyi, 派灭净(pymetrozine), pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, Spin 〇s (spin〇sad), Spirodiclofen, Spir〇mesjfen, spirotetramat, sulf〇xafl〇r, tebufenozide, chlorpyrifos Tetramethrin ), tetramethylfluthrin, thiacl〇prid, thiamethoxam, thiodicarb, thiosultap-sodium, tai ning (trai) A group consisting of all strains of 〇methrin), triazamate, triflumuron, Bacillus thuringiensis, and Nucieo polyhydrosis viruses. 20 11_ A composition for protecting an animal from parasitic pests of an invertebrate comprising a parasiticidally effective amount of a compound as claimed in claim 3 and at least one carrier. 213 201204254 12. Method for measuring animal pests, which comprises the contact of the compound described in item 1 of 'Biological* Animal Diseases'::: 13.==1 The method of the invertebrate pest environment', The biologically effective amount is in contact with the German compound. Bao I: A seed or a plant grown therefrom is exempt from the invertebrate method, comprising contacting the seed with a biologically effective amount of the request "a compound of the formula." The seed is coated with a compound as described in the composition of claim 1, the composition comprising a film former or a binder. 15 16. A treated seed comprising an amount of Pre-treatment seed weight 0 0001 to 1% of the compound described in claim 1. S 214 201204254, IV. Designated representative figure: A : (1) The representative representative of the case is: (None) figure. ' (2) A brief description of the symbol of the representative figure: 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: 5