TW201020252A - Diaza-indole derivatives and their use as fungicides - Google Patents

Abstract

The present invention relates to novel compounds of the formula (I): in which any one of G1, G2 and G3 is N and the other two of G1, G2 and G3 are CR8, CR1 or CR2, such that when G1 is not N, G1 is CR8; when G2 is not N, G2 is CR1; when G3 is not N, G3 is CR2 and X1, X2, R1, R2, R3, R4, R6, R7, and R8 are as defined in the claims. In particular, the invention relates to use of these compounds in methods for the control and/or prevention of fungal infection in plants. The invention also relates to compositions containing these compounds as well as methods for preparing these compounds.

Description

201020252 VI. INSTRUCTIONS OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to novel fungicidal activity, a composition comprising such novel compounds, and a method thereof for controlling and/or preventing fungal infections of plants the use of. In addition, the present invention relates to a process for preparing a novel compound of the present invention. [Prior Art] Some two are described in w〇 99/20624. It is used for the prevention and treatment of human and animal diseases (although not caused by fungi). In 2007/1 10868, w〇 2〇〇7/〇472〇7 and w〇 9_, there was also a related compound $' but these compounds were also independent of controlling fungi in plants. Certain diterpenoids have been found to have fungicidal activity and, in particular, activity against phytopathogenic fungi. SUMMARY OF THE INVENTION The present invention provides a method for preventing and/or controlling fungal infections in plants and/or plant propagation materials, which comprises applying a compound of formula (I) to a plant or plant propagation material:

(I) where: G ' G2 and G3 are either N and G2 and the other two of 201020252 ▲ are CR8, CR1 or CR2, so that when G! is not N, G1 is CR8; when G2 is not When N is N, G2 is CR1; when G3 is not N, G3 is CR2; X1 is N or CH; X2 is N or CR5; R1 is: '(1) hydrogen, halogen, hydroxyl, cyano or nitro; • ( ) optionally substituted alkyl, optionally substituted alkenyl or, optionally substituted alkynyl; ❹ ... (iii) optionally substituted aryl, optionally substituted heteroaryl And optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; or (iv) -C(〇)R10 . -C(O)NR, 0Rn > -C(S)NRiorm ' -C(NOR丨0)Rn, _c(〇)〇Rio, _〇Ri〇, _SRl0, -S(〇)R|〇, -S(O)NR,0R11 , -S (O)2NR,0Rn ^ -S(0)2R,0 ^ -NR10r" ' -P(0)(ORl〇)(OR") or -OPCOKOR10)(0111 丨); R2 is: ❹ (i) hydrogen , halogen, hydroxy, cyano or nitro; (11) optionally substituted alkyl, optionally substituted alkenyl, alkoxy substituted or substituted alkoxy; (ill) Vision Substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; or (iv) -C (〇) R1〇, -C(O)NR, 0Rm , -C(S)NRI0Rm ' _C(N〇R,〇)Rn, -C(〇)〇R]0, -〇R丨〇, _SRi〇 , _S(0)Ri〇, 201020252 -S(O)NRl0Rn ^ -S(O)2NR10R" . -S(〇)2Ri〇. _Nr.〇ri., -p(o)(or10)(orm) or -opcoxorMxor"); R3 is: (i) hydrogen, hydroxy, cyano or nitro; (ii) optionally substituted alkyl, optionally substituted, dilute (including, as appropriate, substituted (iii) optionally substituted aryl 'optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or Alternate cycloalkenyl; or (iv)-C(0)R,2>-C(0)0R,2>-〇R12> -OC(〇)R12. -S(〇)2R12 or- NRi2R13 ; R4 is: (i) nitrogen, A, hydroxy, cyano or nitro; (ii) optionally substituted alkyl, optionally substituted, or optionally substituted alkynyl (i ii) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; Or (lV)-C(〇)R14, -C(〇)〇R14, -C(NOR14)R15, -〇R丨4, -SR!4, -S(0)NR, 4R15, -s(〇 2R14 or -nr14r15; R5 is: (i) hydrogen, halogen, hydroxy, cyano or nitro; (ii) optionally substituted alkyl', optionally substituted alkenyl or optionally substituted alkynyl 201020252 (iii) -C(0)R16, -C(0)OR16, -〇R16, -SR〗6, -S(0)R丨6, -S(0)NR16R17, -S(0)2Ri6 Or -NR]6Rl7; R6 is: (i) hydrogen, halogen, hydroxy, optionally substituted alkoxy or cyano; (ii) optionally substituted aryl, optionally substituted heteroaryl, * optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or, as appropriate, substituted cycloalkenyl; or (iii) -C(0)0R18, -SR18, -NR18R丨9, -C(0)NRuR19, ❹-N=CR20 or, C(=NR18)NR19R20; R7 is: (i) hydrogen, a hydroxy group, a cyano group or a nitro group, (ii) an optionally substituted alkyl group , (iii) -NR2, R22; R8 is: (i) hydrogen, halogen, hydroxy, cyano or nitro, (ii) optionally substituted alkyl, or ® (iii) -nr21r22; R (7), RH, Ru, Rl5, Rl6 and r17 are independently: (i) hydrogen, halogen, hydroxy, cyano or nitro; (ii) optionally substituted alkyl, optionally substituted alkoxy, optionally substituted Alkenyl or, optionally substituted alkynyl; or (111) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkane Substituted or optionally substituted cycloalkenyl; 201020252 R丨2 and Rn are independently: (i) hydrogen, _, hydroxy 'cyano, nitro or _NR21R22; (ii) optionally substituted alkyl a substituted alkoxy group, optionally substituted alkenyl group or, optionally substituted alkynyl group; or (iii) optionally substituted aryl group, optionally substituted heteroaryl group, optionally Substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; R18 and R19 are independently: (i) hydrogen; (ii) optionally substituted Alkyl, optionally substituted alkenyl or, optionally substituted alkynyl; (1 11 ) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally a substituted heterocyclic alkyl group or a bad dilute group as appropriate; or (iv) -C(S)R ^ -C(0)R23 ' -S(〇2)r23 λ -C(〇 ) OR23 ' -OR23 or c(o)nr23r24 ; R20 is: (i) hydroxy, (Π) optionally substituted alkyl or optionally substituted alkoxy, or (Ui) -NR2 丨R22 or _ n=cr21r22 ; R21 and R22 are independently: (i) hydrogen; (Π) as the case may be substituted, or as appropriate, or alkynyl substituted according to 201020252; (iii) as the case may be Substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; or (iv) -C(0 R25 and R24 are independently: (i) hydrogen or hydroxy; (ii) optionally substituted alkyl, optionally substituted alkenyl or substituted alkynyl; or (iii) Depending on the situation, the aryl group is replaced, as appropriate a heteroaryl group, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; and R25 is optionally substituted alkyl, optionally substituted alkene Or alkynyl substituted as appropriate; and optionally, independently, (i) R1 and R2, (ii) R1 and R3 '( iii ) R2 and R3 '( iv) R3 and R5, (v) R5 And R6, (vi) R5 and R18, (vii) R and Rl9, (v) R·14 and H15, and/or (ix) R18 and R19 form an optionally substituted 5- to 18 ring atom Aryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; or isomers thereof, tautomeric Body, N_oxide or salt (including N-oxide salts). [Embodiment] 9 201020252 Unless otherwise stated, the following terms used in the specification and claims have the following meanings: "Alkyl" means a linear saturated monovalent hydrocarbon having 1 to 8 carbon atoms. Or a branched chain saturated monovalent hydrocarbon group having 3 to 8 carbon atoms, such as methyl methacrylate, ethyl 'n-propyl, isopropyl, n-butyl 'second butyl, isobutyl, " tert-butyl, N-pentyl, n-hexyl and the like. Preferably, the linear alkyl group contains ^ 6 : a solid ' more preferably contains 1 to 4 carbon atoms and is preferably selected from methyl 'ethyl or n-propyl. Preferably, the branched alkyl group contains 3 ^ atoms and more preferably is selected from the group consisting of isopropyl 'second butyl, iso-yl or tributyl" alkenyl means 2 to 8 having at least one double bond. A linear monovalent hydrocarbon group of a carbon atom or has a 3 ', a group such as a vinyl group, a propyl group, a monovalent foreign matter (tetra) group, and the like. If appropriate, it has a (!> or (2> configuration. More ancient) alkenyl group and is more preferably selected from the group consisting of a vinyl group, a propyl group, a main group of six anionic propylene groups, a propan-2-alkenyl group, and a propyl-i group. 2_1 base, but-1-enyl, butyl __A, madyl, butyl 3-diyl, butyl-1,2-dienyl and butyl, alkenyl. Preferred, branched alkenyl Containing 3 best is selected from the group consisting of 1-methylvinyl, anti-atom and more I 甲基 methyl propyl, 1-methyl-secret-mercaptopropyl propyl and methyl propyl _2 - dilute:, ene The base may contain at least 2 meso-', two conditions, such as a double bond between C--12 m 3 adjacent carbon atoms, such as a dienyl group and the like. If the person is pentyl-alkenyl, _ 1,2· Configuration. Preferred Α Λ 1 1 σ, 'The alkenyl group may have (8)- or (8)-the living group is a propan-12-dienyl group. "Alkynyl group" means at least _ &quot a three-bonded linear monovalent hydrocarbon group having 2 to 8 carbon atoms of 201020252 or a branched chain monovalent nicotyl group having 4 to 8 carbon atoms such as an ethynyl group, a propynyl group, and the like. Preferably, a linear chain Alkynyl: 2 to 6 carbon atoms and more preferably selected from ethynyl, propionyl alkynyl, propyl | alkynyl Preferably, the branched bond block group has 4 to 6 carbon atoms and more preferably is selected from the group consisting of: methyl propyl-2-block group, ^methyl group. But-1-propanyl, κmethylbutyrynyl, bromobutan-3-yl and butyl-3-ynyl. τ ❹ Ο "alkyl" means linear saturation with from i to 6 carbon atoms A divalent furnace base or a branched bond having 3 to 6 carbon atoms to saturate a divalent nicotine group, for example: methyl group: exoethyl group, propyl group, 2-methyl group propyl group and the like. A divalent group of an alkyl group as defined herein. "Extend alkenyl group" means a straight-chain divalent hydrocarbon group having 2 i 6 or a branched chain 2 having 3 3 6 carbon atoms containing at least one double bond: a hydrocarbon group 'For example, a vinyl group, a propyl group, and the like. Preferred is a divalent group of an alkenyl group as defined above. Soil ', ', "cycloalkyl" means having 3 to 8 ring carbons. The saturated monovalent ring furnace base. Preferably, the cycloalkyl group contains 3 to 6 ring carbons, more preferably selected from the group consisting of: a group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group. Said to have 3 to 8 ring carbons, preferably 4 a monovalent monounsaturated or diunsaturated hydrocarbon group of a ring carbon such as a cycloalkyl group, a cyclopentenyl group and a cyclohexyl group. A dilute "heterocycloalkyl group" means having 3 to 8 ring atoms, preferably a monovalent cyclic group having 3 6 or 4 to 6 ring atoms, which contains 丨, 3 or 3 independently selected from 〇 and s(〇) n (wherein 打 to 2 蝥11) 201020252 ring hetero atom 'The remaining ring atom is carbon carbonyl, which has no right 雔 _ one or two carbon atoms can be (but not limited to) ethylene oxide, "former + _ clothing example package and Ritually, 虱 虱, Π 喃, I 3 - ϋ rV' « 虱 夫 夫 四, tetrahydro / i, 3- 乳 戊 环 ' 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 嚼 哌 哌 哌 哌 哌Azacyclohexane, 啾*1, pyrrole (tetra) and cut. Better, mixed second generation #, 咪心定,. Compared with the ring family: to; heterozygous base contains -. And / or - a group of 3 to 5 ring atoms. "Aryl" means a cycloaromatic hydrocarbon group having 6 to 10 ring carbon atoms. Suitable aryl groups include phenyl and naphthyl groups, which are defined as having a monovalent monocyclic or bicyclic aromatic pentyl group having 5 to 10 ring atoms, preferably having 5 or 6 solids. It contains one, two, four or four ring heteroatoms independently selected from N and ws, and examples of the remaining ring atom squares include, but are not limited to, pyridyl, pyrimidine, and fluorenyl , iso (tetra) and tetra. The base, heterocyclic ring or (heter〇cycle) actually has 3 to 8 ring atoms' preferably has 3 to 6 or 4 to 6 rings. Or a fully unsaturated or partially unsaturated monovalent cyclic group containing [[, 2 or 3 independently selected from the group consisting of N, 〇 and S(0)n (where n is an integer from 〇 to 2) Hetero atom. The heterocyclic ring can be a heteroaryl or heterocycloalkyl group as defined above. 'Alkoxy" means a monovalent group -OR, wherein R is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, Optionally substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl or, as appropriate, substituted 12 201020252 heteroaryl. In particular, R may be optionally substituted & ^, optionally substituted by t C2_6, optionally substituted & alkynyl, optionally substituted C3.6 cyclofil, optionally substituted 3 members _6 negative heterocyclic group,

Depending on the situation, t C "cyclical, optionally substituted phenyl or optionally substituted heterophenyl. R can be helmeted, 0 γ % A is not · " κτ is optionally substituted aralkyl a heteroaryl group substituted or optionally substituted. Preferably, the alkoxy group is selected from the group consisting of methoxy, ethoxy, oxime 1-methylethoxy, propoxy, b-methylpropoxy and 2—Methylpropoxy. More preferably, alkoxy means decyloxy or ethoxy. “Alkoxyalkyl” means a monovalent straight-chain group _Ra0Rb, wherein Ra is optionally substituted a group, for example, a C1.4 group which is optionally substituted, and Rb is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted, as appropriate Substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl or optionally substituted heteroaryl. In particular, Rb can be optionally substituted by C, .6 alkyl, optionally substituted C2 6 dilute, optionally substituted C2.6 alkynyl, optionally substituted c3 6 ring burned a 3-member-6-membered heterocyclic alkyl group, optionally substituted, as a c-ring, optionally substituted, or optionally substituted, heterocyclic group. Rb may be as herein The definition in the definition of 'clear condition' is replaced by < the appearance of the base or the genus, and the 隋 经 以 杂 。 。 。 。 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 基 意 意 意 意 意 意 意 意 意 意 意 意It is gas or fluorine. "Haloalkyl" means a radical as defined above substituted with one or more of the same or different atoms. The substituted base can be i-based. Letter 13 201020252 Examples of representative bases include, but are not limited to, a methyl... methyl, 2-fluoroethyl, 2-trifluoroethylmethyl squirrel ethyl, 2-male 7 fluoropropyl , 3-chloropropyl, 2_di#, ethyl, 3-indol-1-ylethyl and hydrazine _ two said - fluoropropyl. <RTIgt;""""""""""" The substituted scorpion is substituted with a dentate thiol group. Examples of haloalkenyl groups include, but are not limited to, 2·di-vinyl, 2-gas; strepothyl, 5-bromopent-3-enyl, and 3-dipropan-2-alkenyl. And "arylalkyl" means a monovalent group _RaRb' wherein Ra is an alkylene group or a thiol group and each group is defined as defined above. "Heteroaralkyl" means a monovalent group _RaRb wherein Ra is alkyl or alkenyl and Rb is heteroaryl, each group being as defined above. "醯基" means a monovalent group in which 'R is hydrogen, as the case may be substituted (4), depending on the <lf condition substituted alkenyl' (4) substituted block, now substituted cycloalkyl 'Substituted heterocycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl or optionally substituted heteroaryl. In particular, R may be optionally substituted Cw alkyl, optionally substituted C2. 6 alkenyl, optionally substituted c2 6 alkynyl, optionally substituted C; A sulphur-based, optionally substituted, 3-membered-6 heterocycloalkyl group, optionally substituted (: 4-6 cycloalkenyl, optionally substituted phenyl or optionally substituted heterophenyl). "基" means a monovalent group _〇C(〇)R, wherein R is hydrogen, alkyl as appropriate, alkyl substituted, optionally substituted alkenyl, optionally substituted block, optionally substituted a cycloalkyl group, optionally substituted heterocycloalkyl group, 201020252 optionally substituted cycloalkenyl group, optionally substituted aryl group or optionally substituted heterocycle group. In particular, R can be regarded as The cf-based, substituted C2.6 dilute, as appropriate, C-substituted, as appropriate, replaced by the cyclohexyl group, as the case may be replaced by 3 Γ · 6, the soil is bad An alkyl group, optionally taken as a C 4.6 cycloalkenyl group, optionally substituted phenyl or optionally substituted heterophenyl.

The groups defined above, in particular alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl, may be unsubstituted or may be passed through one or more Substituted independently of a substituent selected from the group consisting of: hydroxy; cyano; alkyl (optionally substituted by cyano), such as C?-4 alkyl; haloalkyl, such as Cni alkyl; alkenyl, for example C2_4 alkenyl; on the alkenyl group, for example C:2·4 ii alkenyl; alkynyl (optionally substituted by _c(〇)〇R), for example C2·4 alkynyl; haloalkynyl, for example C2_4 Haloalkynyl; cycloalkyl (optionally substituted by cyano, i!, hydroxy or thiol), for example C3-6 cycloalkyl; heterocycloalkyl, for example 3 member-6 heterocycloalkyl; aryl (Substituted by _ sin), such as phenyl; heteroaryl, such as heterophenyl; alkoxy (optionally substituted by alkoxy or fluorenyl), such as 〇_c!_4 alkyl; _c (〇 ) R ; _c(〇)〇R ; -SR ; -S(〇)R ; -S(0)2R ; _s(0)NRR,; -0S(0)NRR,; -P(0)(OR) (〇R,) ; -〇(P)(〇)(〇R)(〇R,) ; -NRR5 ; -NHC(0)〇R' ; _C(0)NRR' ; _〇_N = CRR, Or three Alkylalkyl, wherein R and R' are independently hydrogen or alkyl (eg, Ci-4 alkyl), alkoxy (eg, -Ο-C, .4 alkyl), haloalkyl (eg, C|_4 haloalkyl) Alkenyl (e.g., C2·4), haloalkenyl (e.g., c2_4 haloalkenyl), fast radical (e.g., C2·4 alkynyl), cycloalkyl (e.g., c3-6 cycloalkyl), heterocycloalkane Base, aryl 15 201020252 base (eg stupid) or heteroaryl (eg heterophenyl). In particular, R and R' are independently hydrogen or alkyl (specifically, methyl or ethyl). Substituents which are preferably selected as appropriate are alkoxy groups (specifically, decyloxy or ethoxy), hydroxy, cyano, halogen (specifically, fluorine, gas or bromine), heterocycloalkyl (specific In the case of ethylene oxide or tetrahydrofuran), heteroaryl (specifically, acridinyl), -C(0)0R (wherein r is hydrogen or alkyl (specifically, methyl or ethyl)) And a trialkylalkylene group (specifically, a trimethylsulfonylalkyl group). For example, alkyl, alkenyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, aryl and heteroaryl groups may optionally be selected from halogen, hydrazine, C, and optionally substituted. 4 alkyl, Cl_4 haloalkyl, _NH 2 and cyano; in particular selected from halogen. For the avoidance of doubt, the "optionally substituted" group is unsubstituted or substituted with ~ or a plurality of substituents selected from the substituents listed in the above paragraphs. The compounds of formula (I) may exist in different geometric or optical isomeric forms or in different tautomeric forms. One or more chiral centers may be present, in which case the compound of formula (I) may be a pure enantiomer, a mixture of enantiomers, a pure diastereomer or A mixture of diastereomers is present. A double bond may be present in the molecule, such as a C=C or C=N bond. In this case, the compound of formula (1) may exist as a single isomer or a mixture of isomers. Metamorphic center. The present invention encompasses all such structures and tautomers and mixtures thereof in all ratios as well as isotopic forms such as deuterated compounds. Suitable salts of the compound of formula (1) include acid addition salts such as those with or without 16 201020252 organic acids (such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid or phosphoric acid) or organic carboxylic acids @ (such as oxalic acid, tartaric acid, lactic acid, A salt formed from butyric acid, f benzoic acid, caproic acid or phthalic acid or a sulfonic acid such as decanesulfonic acid, benzenesulfonic acid or methanesulfonic acid. Other examples of organic carboxylic acids include functional acids such as trifluoroethyl sulfonium. The present invention encompasses all such salts of the compounds of formula (1). The N-oxide is an oxidized form of a tertiary amine or an oxidized form of a nitrogen-containing heteroaromatic compound which is described in various books, for example, in "Heter〇cycuc

N_〇XldeSj, Angel〇 Albini and Silvio Pietra, CRC Press, Boca Raton, Flonda, 1991. The present invention encompasses all such N-oxide forms of the compound of formula (1). In a more preferred embodiment of the invention, preferred groups of X1 and X2 and Ri to R25 are as described below, in any combination thereof. Preferably, 'G' is CR8, G2 is CRi and 亇 is N. Preferably, X1 is c Η. Preferably, X2 is CR5. More preferably, χ 2 is CH. Preferably, R1 is: (i) hydrogen, halogen or cyano; (η) optionally substituted Ci0 alkyl, optionally substituted C26 alkenyl or, optionally substituted C2 6 alkynyl; or m) an optionally substituted aryl group (for example, a phenyl group substituted as appropriate) or -C(〇)R10, · which may be used as appropriate in the case of the singularity and deduction; It is defined and more preferably selected from the group consisting of a hydroxyl group, a ruthenium group, a _±-alkoxy group (e.g., a-0-C" alkyl group), a halogen, and a trialkyl decyl group. 17 201020252 More preferably 'R is hydrogen, pixel, cyano, optionally substituted Ci_6 alkyl, optionally substituted CM alkenyl 'substituted C2 6 alkynyl, optionally substituted aryl ( For example, as the case may be replaced by a stupid base) or -C(0)R. Even more preferably, R1 is hydrogen, chlorine, bromine, cyano, methyl or 2,tridecylalkyl-ethynyl. Most preferably, Ri is hydrogen, gas or sulfhydryl. Preferably, R2 is: (hydrazine hydrogen, or (π) optionally substituted Cw alkyl or optionally substituted 〇Ci6 alkyl, wherein the substituents selected as appropriate are as defined above. 'R2 is hydrogen or Cw alkyl. Preferably, R3 is: (i) hydrogen or hydroxy, () optionally substituted c, · 6 alkyl, optionally substituted C2 6 dilute or optionally Substituted C2-6 alkynyl, ^ () depending on the substituted cycloalkyl group, such as optionally substituted C3-6, or (lv) -C(0)r12, _0Rl2, _c (〇 ) 〇r12, - ❹ -S(0)2R12; The substituent selected for the seedling is in all cases as defined above and more preferably selected from the group consisting of cyano, acetyl, hydroxy 'C丨-4 Alkyl, C2_4 alkenyl, pyrenyloxy (example: ^r ^ _ _Cl-4 alkyl) (optionally via alkoxy (eg -O-Ci-4 pit) or 酼I γ , such as 6 For example, -(0)c_Cl-3alkyl) is substituted, cycloalkyl (for example, 3-membered group), cycloalkenyl (for example, C3·6 cycloalkenyl), heterocycloalkyl (example: %) , aryl (eg stupid), heteroaryl (eg 18 201020252 heterophenyl), -NH 2 , trialkyl hydrazine Alkyl, -C(〇)R and -C(0)0R (wherein R is hydrogen, methyl or ethyl). More preferably, R3 is hydrogen, hydroxy, -(:(0)1112, -OR12, -C(0)0R12, -〇C(0)R12, -S(0)2R12, optionally substituted C , 6 alkyl, optionally substituted C 2-6 alkenyl, optionally substituted c 2.6 alkynyl, optionally substituted cycloalkyl (eg, optionally substituted C 3-6 cycloalkyl). Most preferably, R3 is hydrogen, cyanomethyl, aminoethyl, aminopropyl, vinyl, prop-2-enyl, prop-2-ynyl, propane-1,2-dienyl, Oxyfluorenyl, 2-fluoromethyl, 2-fluoroethyl, -〇CH2C^:H, -OCH2OCH3, -OCH2CN ' -〇CH(CH3)CN, _0(:Η2(:Η = (:Η2 or Benzyl. R3 may be optionally substituted c, .6 alkyl, optionally substituted C2_6 or optionally substituted C2.6 alkynyl, wherein alkyl, alkenyl and alkynyl The substituents selected in the case are selected from the group consisting of cyano, methoxy and halogen. For example, 5' R is C3-4 alkenyl or C3_4 alkynyl. Preferably, R4 is (i) hydrogen or halogen, (i depending on the case) Substituted (: 2·6 alkynyl, (111) optionally substituted aryl (eg, substituted as appropriate) or substituted as appropriate An aryl group (e.g., optionally substituted heterophenyl); wherein the substituent selected as appropriate is, in all cases, as defined above and more preferably selected from the group consisting of a trans group, a halogen (specifically, fluorine or gas), From the base (for example Cm haloalkyl), mercapto (such as alkyl) and C" alkyl (specifically, fluorenyl). The alkyl group can be a Cl.4 haloalkyl group. Substituting one alkynyl group or an aryl group substituted according to the case of 201020252 (for example, a substituted base as appropriate) or a substituted heteroaryl group (for example, a heterophenyl group optionally substituted). More preferably, R4 is phenyl, 3-decylphenyl, 3-trifluorodecylphenyl, 2-fluorophenyl, 3-phenylphenyl, 4-fluorophenyl, 2,5-diphenyl , 3-methyl-4-carbene, 2,4-difluorophenyl, 2,6-difluorophenyl or 2,4,6-difluorophenyl. R4 can be 1 to 3 as appropriate A phenyl group independently selected from the group consisting of: (丨.4 alkyl, Cw haloalkyl, and halogen), for example, R4 is a phenyl group optionally substituted by 1 to 3 halogen atoms. , R5 is: 〇 (ϋ hydrogen or halogen, (11 Substituted C i · 6 alkyl 'Substituted c2_6 alkenyl or optionally substituted C 2_6 alkynyl, or (n i ) optionally substituted aryl (eg optionally substituted benzene)

Base), base), alkyl) ring rare J 6 member heterocyclic ring);

More preferably, it is selected from the group consisting of halogen, cyano, hydroxy, and C alkyl. More preferably, R5 is hydrogen or halogen. Preferably, R6 is: (hydrogen, chlorine, hydroxyl or ethoxy)

In the case of hydroxy or C, as defined above, • 4 13⁄4 generation alkyl and Ci-4 20 201020252 (11) optionally substituted aryl (eg, substituted as appropriate), optionally substituted heteroaryl (e.g., optionally substituted heterophenyl), optionally substituted cycloalkyl (e.g., optionally substituted cycloalkyl), optionally substituted cycloalkenyl (e.g., optionally substituted c4 6 ring) Alkenyl) or optionally substituted heterocyclic ring formed with R5 as defined above (eg, 5- or 6-membered heterocyclic ring), or (Hi)-C(〇)〇R18, -NR"Rl9 (eg NH2) ) or _n = cr2〇; The substituents selected in the case of 纟 are in all cases as defined above. For example -NHR19). Most preferably, R6 is 1,4-alkyl, such as ethyl, isopropyl, more preferably, R6 is hydrogen or -NR18R19(-NHC(0)R23, wherein R23 is preferably c or cyclopropyl or cyclobutyl The alkyl group or R19 is -C(0)R23, and r23 is C2-4 alkynyl or C3_4 cycloalkyl. For example, R6 may be hydrogen or .Rl9, and the towel Rl9 is hydrogen, optionally via a hydroxyl group. Or a C 4 alkoxy group (which may be substituted by a hydroxy group) is preferably a" -4 alkyl, C2.4 alkenyl hydrazine, and R7 and R8 are independently: (i) hydrogen, a trans group or a cyano group; Substituents, cyano groups, hydroxyl groups, and C, _6 alkyl groups, which are substituted as appropriate, are as defined above and more preferably selected from the group consisting of: (i.e., C 1 -4 generation) Or (ii) -NR2丨R22; thiol, cyano, -NR2, R22 or R and independently independently chloro, more preferably, R7 and R8 are independently hydrogen, optionally substituted C , · 6 alkyl. Best, 21 201020252 base or NR2 | R22. r16 and R17 are independently preferred, Rl., Rll, R14, Rl5, [i) hydrogen, or L 11) optionally substituted C a 6 alkyl group, optionally substituted c2 6 alkenyl group or optionally substituted Cw alkynyl group, The substituents selected in the above-mentioned case are as defined above and more preferably selected from the group consisting of a base H, a cyano group and a calcined oxygen group (e.g., -〇-cU4 alkyl group). _ K Han feet and feet are independently hydrogen or

Substituted Ci 3 alkyl. Most preferably, Rl 〇, Rll, rU, Ri5, and Rn are independently hydrogen, methyl or ethyl. Preferably, 'RU and rH are independently: (1) optionally substituted c, _6 alkyl, optionally substituted c2 (diluted 'optionally substituted C2 6 alkynyl, or 1 () as appropriate Substituted (: 3 δ cycloalkyl or optionally substituted q cycloalkenyl; ^ wherein the substituents selected as appropriate are in all cases as defined above and more preferably selected from the group consisting of hydroxy 'halogen, cyano, Alkoxy (eg, alkyl), cycloalkyl (optionally substituted by hydroxy or methyl, eg, Cw cycloalkyl), cycloalkenyl (optionally substituted with hydroxy or thiol), eg c46 cyclomethine -C(〇)〇R and -〇S(〇)NRR, (wherein R and R, independently hydrogen, alkyl (e.g., C" thio), alkenyl (e.g., C" dilute) or fast radical ( For example, base)), better 'R & R _ site is an optionally substituted base (including C"me" burnt base), as appropriate, replaced by c "sweet base or as appropriate 22 201020252 Preferably, 〜13 is independently cyanomethyl, (1-indenyl)- aryl fluorenyl, and propylene-2-alkenyl, propyl-2-ynyl or carbaryl A. Preferably, R18 is: 丞i) hydrogen (i contempt Substituting the alkyl group, optionally, an alkenyl group or, as the case may be, a substituted c2 6 alkynyl group, 2·' (a heterocyclic ring formed by substitution with Rl9, such as a 56-membered heterocyclic ring, as the case may be, Or steam or

(iv) -C(〇)r23. .C(〇)〇r23_S(〇)2r23 ^.C(〇)Nr23r24; wherein the substituents selected as appropriate are in all cases as defined above and are better It is selected from the group consisting of hydroxyl, cyano, halogen, and alkoxy (eg, 〇 alkyl). More preferably, R is hydrogen, Cl-4 alkyl, C2_4 alkenyl or c2-4 alkynyl. The heart of the heart is hydrogen, ethyl, isopropyl, propylene, and bis-alkynyl. Preferably, R19 is: (i) hydrogen, (u) optionally substituted C. 6 alkyl, optionally substituted alkenyl or optionally substituted c2-6 alkynyl, 2' ( Hi) optionally substituted aryl (for example, optionally substituted), optionally substituted heteroaryl | (e.g., optionally substituted heteroalkyl), optionally substituted cycloalkyl (e.g. Optionally substituted c36 decyl), optionally substituted cycloalkenyl (eg, optionally substituted c/cycloalkenyl) or optionally substituted heterocycloalkyl (eg 3 members _6 mourning) ^ 23 201020252 Conditionally substituted heterocycloalkyl) or optionally substituted with RU (for example, a 5- or 6-membered heterocyclic ring), or, (H(S)R23 ' -C(〇)r23, _c(〇)〇r23, _s(〇)2R -c(o)nr23r24, ^ wherein the substituents selected as appropriate are in all cases as defined above and more preferably selected from the group consisting of hydroxyl, cyano, halogen, Alkoxy (for example, 〇C疋=:, 嶋 (for example, c "cycloalkyl"), cycloaliphatic (for example, C "cyclo 4]), and heterocyclic (for example, 3-member-6-membered heterocyclic) ; 23 'Bu, R!9 is hydrogen, C(S)R23, _C(〇)R23 or -C (°) 〇R23 or spectroscopy, Ci-4 cis base. Best, R丨9 is hydrogen 'isobutyl, _c(〇)R or -C(〇)OR23. Preferably, R2° is Preferably, R21 and R22 are independently: (i) hydrogen, (in the case of a substituted C, h> |, a corresponding Cl-6 group, such as a Cw alkyl group, wherein The substituents selected as described above are as defined above and are more preferably selected from the group consisting of a hydroxyl group, a chaotic group, a dentate, an alkoxy group (e.g., _〇_c. 丨·4 pit base), a fluorenyl group. (eg (QK-Ch fluorenyl), cycloalkyl (eg, DP, eg h. 6 cycloalkyl), cycloalkenyl (eg c "% alkenyl"), heterocycloalkyl (, N ' '6 More preferably, heterocycloalkyl) or C ill) -C(0)0R25 fluorenyl hydrazine ❹ more preferably, R21 and R22 are independently 戍 y + 21 勹 1 砚 in case the substituted Cm alkane is independently H, Methyl or ethyl. Preferably, R23 and R24 are independently: (i) hydrogen or hydroxy, 24 201020252 (11) optionally substituted C!·6 alkyl, optionally substituted CP alkenyl or a substituted C2_6 alkynyl group, or (a cycloalkyl group substituted according to the situation (for example, C3·6 ring hospital as the case may be substituted) And optionally substituted cycloalkenyl (e.g., optionally substituted C4_6 cyclyl) or optionally substituted aryl (e.g., optionally substituted phenyl); wherein the substituents are optionally employed at all The conditions are as defined above and more preferably selected from the group consisting of hydroxyl, halogen, cyano, C, -4 alkyl, alkoxy (eg -0-C, .4 alkyl), cycloalkyl (eg C3 6 Cyclone), cycloalkenyl (eg, C4-6 cycloalkenyl), and _C(0)0R (wherein R is cycloalkyl (eg, ring-based) or cycloalkenyl (eg, C4 6 cycloalkenyl D). Further, R and R are independently hydrogen, a thiol group, and optionally a C. 6 alkyl group (e.g., Ci. 6 alkyl 〇 C C C 1-6 alkyl), optionally substituted c20 alkenyl Optionally substituted cycloalkyl (e.g., optionally substituted c3_6 fluorenyl) or optionally substituted cycloalkenyl (e.g., optionally substituted C"cycloalkenyl). Best, R23 and R24 is independently methyl, ethyl, isopropyl, decyloxy, cyclopropyl or cyclobutyl, wherein cyclopropyl or cyclobutyl may be selected from one or more selected from the group consisting of cyano and halogen (more Preferably, the fluoro), c, _4 alkyl (more fluorenyl or ethyl) or a substituted alkenyl substituent is substituted. Preferably, R25 is C, -4 alkyl. More preferably, R25 is a fluorenyl group. Ethyl, propyl or 2-dimethylethyl. In a preferred embodiment, when R3 is hydrogen, R6 is not hydrogen. More preferably, R is hydrogen and R6 is _NR18R19. More preferably, R3 Is hydrogen and r<5 is -NHRl9. More preferably, R3 is hydrogen and R6 is _NHC(〇)R23. 25 201020252 In another preferred embodiment, R6 is hydrogen 6 on 3 |? and R is not hydrogen More preferably, R6 is hydrogen and R3 is -OR丨2 or optionally substituted 1/alkane a group, a C2.4 alkenyl group (e.g., c3.4 propylene dibasic) or a c2 - 4 block.

Is a gas methyl group, an aminoethyl group, an aminopropyl group, a propyl group, a propylene group 2: a aryl group, a propyl group, a 1,2-dienyl group, a methoxymethyl group, a 2-fluoromethyl group, a fluorene group cH2c<H ' -OCH2OCH3 ' -OCH2CN ' -〇CH(CH3)CN 0 For example, the method of the invention may use a compound of formula (Ia):

The compounds of formula (Ib) can be used in the process of the invention as defined above for the compounds wherein: χΐ, χ2, R1, R2, R3, R4, R6 and formula (I) are in any combination:

X ' R2' R^' p6x r7 h p® I) compound household "R R, R is as above (Ib)

Where X is the meaning of the combination, in any combination. Process 1 of the Invention * Compounds of formula (Ic) can be used: 26 201020252

Wherein X1, X2, R1, R3, R4, R6, r7. and R are as defined in the compound of formula (i), in any combination thereof, 'in a particular embodiment', the method of the invention uses the formula ((4) Compound:

Ο where: G1, G2 and G3 are N and the other two of G1, G2 and G3 are CR8, CRi or CR2 'so that when not n, Gl is CRS; when G2 is not N' G2 is CR1; when G3 is not N, G3 is CR2. R1, R2, R3, R4, R6 and R8 are as defined above for formula (丨), in any combination thereof; and preferably in any combination of the following Form: R1 is hydrogen, halogen, cyano, optionally substituted C, · 6 alkyl (specifically, optionally substituted C, -4 alkyl and most specifically, as appropriate) Or a substituent wherein the substituent is optionally as defined above and more preferably a hydroxy group such as hydrazine-hydroxyethyl or wherein R1 is hydrogen or Cj-4 alkyl; R2 is hydrogen, halogen Or cK4 alkyl; 27 201020252 R is hydrogen '^, cyano, optionally substituted c】 _6 alkyl, optionally substituted c, "抡| γ κ linkage (including C3_6 as appropriate) Propadiene

Base), optionally substituted C"block group, _nr12r13, _〇R-C(0)R12, wherein: β (wide) & base 'alkenyl and alkynyl groups are optionally selected as described above Derogatory and more preferably independently selected from halo & cyano, hydroxy, alkoxy (optionally substituted by alkoxy or fluorenyl, eg _〇_C|-4 alkyl), c" 2-4 alkenyl% alkyl (for example, c "cycloalkyl", cycloalkyl (for example, 6 ring county) 'heterocyclic base (for example, 3 members _6 member heterocyclic alkyl), aryl (example) Phenyl)heteroaryl (eg heterophenyl), _C(〇)R, and, wherein R is 虱2, C|.4 alkyl, C2-4 alkenyl or C2-4 alkynyl, and (b) R and R are, independently, substituted S (for example, c, 6 as the case may be substituted), optionally substituted alkenyl (for example, as the case of U, c2, 6 alkenyl), optionally substituted silk (for example, optionally substituted C2.6 alkenyl), optionally substituted cycloalkyl (eg, optionally substituted by C 3 · 6 % alkyl) or optionally Substituted cycloalkenyl group (for example, γ Ϊ Ϊ 、 、 、 、 、 、 、 、 、 、 、 、 、 说 说Wherein the substituents selected as appropriate are as defined above and/are preferably a functional group, a nitrogen group, a trans group, an alkoxy group (e.g., -0々4 alkyl group), a % alkyl group (e.g., a c3 6 ring group) a cycloalkenyl group (e.g., a ring (tetra) heterocycle; a tyl group (e.g., a member of the group of 6 members), _C(0)R, () or 0S(0)NRR, wherein R and R are independently hydrogen or An alkyl group (for example, C. 4 alkyl); R4 is an optionally substituted aryl group (specifically, a substituted phenyl group or a optionally substituted naphthyl group), optionally a substituent system. For example, 28 201020252 is defined above and more preferably halogen or Cw alkyl; r6 is hydrogen, a nutrient or -nr18r19, wherein: U) R18 is hydrogen, -C(〇)R23, _c(〇)〇r23 or The situation has been replaced by c!·4 hospital base, as the case may be replaced by C: 2 · 4 alkenyl or, as the case may be substituted, c2_4 fluorenyl 'where R 23 is optionally substituted C 4 alkyl, depending on the situation The substituent is as defined above, and (b) R19 is hydrogen, optionally substituted -4-alkyl, optionally substituted Gw alkenyl, optionally substituted c2_4 alkynyl, _c(S)R23 , ® -C(〇)R23 or -C(〇)〇R23' where R2 3 is hydrogen, optionally substituted C|.4 alkyl, optionally substituted C2·4 alkenyl, optionally substituted C2-4 alkynyl substituted C3_6 cycloalkyl or optionally Substituted C3.6 cycloalkenyl 'optionally selected as defined above; R8 is hydrogen, halogen or cN4 alkyl. More preferably, in any combination, R1 is hydrogen, _ group or optionally Substituted C i -4 alkyl 'which preferably has a substituent selected from a hydroxyl group; r 2 and R 8 are independently hydrogen, decyl, ethyl or chloro; R 3 is hydrogen, -OR 12 , optionally substituted Cw alkyl, optionally substituted c2_4 alkenyl or, optionally substituted C2_4 alkynyl; R4 is phenyl, optionally containing at least one selected from halogen and Ct.4 alkyl (specifically, fluorenyl) Substituted by a substituent; R6 is dentate or -NR18R19, wherein Ris is hydrogen, prop-2-enyl or prop-2-ynyl, and Ri9 is -C(0)R23, wherein R23 is hydrogen, methyl , ethyl, isopropyl, 1-methylethyl, 1-mercaptopropyl, 2-dimethylethyl, propyl, 1-methylvinyl, 2-methylpropenyl, butyl-3 Alkenyl, cyclopropyl, hydrazine-methylcyclopropyl Bu-fluoro-cyclopropyl or cyclobutyl. 29 201020252 2 In any combination, R1 is hydrogen, gas or methyl. R and R are independently hydrogen, mercapto, ethyl or gas; R3 is hydrogen 'cyanononyl, propyl-2-alkenyl Or propynyl; R4 is phenyl '2-fluorophenyl' 3-fluorophenyl, t齓 Benzene: 4· oxaphenyl, 3-methylphenyl or 3-methyl-4-fluorophenyl ; R6展-NR R, wherein RU is chlorine and r19 is _c(〇)r2 group, ethyl, isopropyl K is 曱., ^^ propyl, cyclobutyl or 1-decylcyclopropane base. δ, the method of the invention β "using the compound of formula (Ie):

Wherein R1, R2, r3, and 6 are defined, and S-Ganzi 11 is as described above with respect to compound (Id). The compounds of the invention can be used in the process of the invention:

R is as described above for the compound (Id 〇 ig ): wherein R 2 , R 3 , R 4 , R 6 < s, meaning any combination thereof, the method of the invention can be used ( 30 201020252

Wherein R1, R3, R4, R6 and R8 are as defined above for the compound (Id), in any combination thereof.

In a specific embodiment, the method of the invention uses a compound of formula (Ih):

Where: G^G2 and G3 are either n and the other two of G, G2 and G3 are CR8, CR or CR2, such that when G1 is not N, G1 is CR8; when G2 is not N When G3 is CR1; when G3 is not N, G3 is CR2; wherein R1, R2, R3, r4, R6, R7 and R8 are as defined above for formula (I), in any combination thereof;隹: R1 is hydrogen, halogen, optionally substituted Ci-6 alkyl or -C(〇)Ri〇, wherein R10 is hydrogen or CK4 alkyl, and optionally substituted as defined above; R2 Is hydrogen or Ch alkyl; R3 is hydrogen, a radical, optionally substituted c 1 alkyl, optionally substituted C 2-6 alkenyl or optionally substituted C 2 · alkynyl, -C (0 R12 or 31 201020252 -OR wherein R12 is optionally substituted d.4 alkyl, as appropriate. C3.6 cycloalkyl or optionally substituted C4.6 cycloalkenyl, as appropriate The substituents selected are in all cases as defined above and more preferably selected from the group consisting of halogen, cyano, hydroxy, alkoxy (e.g., O-Cw alkyl), cycloalkyl (e.g., C3·6 cycloalkyl) a cycloalkenyl group (for example, a Cw ring) or a heterocyclic group ( Such as 3 members-6 members of cycloalkyl), aryl (such as phenyl), heteroaryl (such as heterophenyl), -nh2, trialkyldecyl and C(0)0R, wherein R is hydrogen, c丨alkyl, Cwalkenyl or c2_4 alkynyl; R4 is optionally substituted aryl, optionally substituted as defined above and more preferably halogen or Cm alkyl; R6 is hydrogen, ii , hydroxy, -O-Cualkyl or -nr18r19, wherein: (a) is hydrogen, -C(0)R23, _C(0)0R23, optionally substituted C丨-4 alkyl, optionally Substituted c2 4 alkenyl or optionally substituted c2-4 alkynyl wherein R23 is optionally substituted c丨·4 alkyl, optionally substituted as defined above, and (b) R19 Is hydrogen, optionally substituted c, · 4 alkyl, optionally substituted C 2 · 4 alkenyl, optionally substituted C 2 4 alkynyl, _C (S) R", Ο -C (〇) R23 Or -C(0)0R23 'wherein R23 is hydrogen, optionally substituted c丨-4, based on the case, substituted C2_4, optionally substituted C2-4 alkynyl, optionally substituted C3_6 cycloalkyl or optionally substituted c4-6 cycloalkenyl group Based group as defined above; R7 is hydrogen 'Cm halo or alkyl; and R8 is hydrogen, halo, C 〖-4-yl or burn NR21R22, wherein R21 and R22 are independently hydrogen or alkyl 32201020252 Cm.

More preferably, in any combination, R1 is hydrogen, a functional group or, as the case may be, 2 C. 4 alkyl, optionally substituted as defined above; R2 is hydrogen or methyl; R3 Is a hydrogen, optionally substituted group, as the case may be taken = C2_4 thin base, optionally substituted C2 4 alkynyl or _〇R|2, wherein R12 is optionally substituted Cl. 4 alkyl, </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; Substituted by a substituent selected from dentate and a Ck4 alkyl group; r6 is a lignin or _NRl8Rl9, the rim Rl8 is hydrogen, a propyl collar or a propyl block, and R1 is _C(〇)R23, wherein The furnace is hydrogen, mercapto, ethyl, isopropyl...methylethyl 1 methyl propyl, 2-didecylethyl, propyl, hydrazine-methyl vinyl, 2-methyl propyl]-lean Base, butyl _3_ dilute, cyclopropyl, "methylcyclopropyl," "propyl or cyclobutyl m hydrogen, gas, fluorine or methyl; a rS is nitrogen, gas, methyl or 2- Oxyethylamino group.

Even more preferably, in any combination, R, is a gas, chlorine or methyl; hydrogen or methyl; R3 is hydrogen, cyanomethyl, propionyl-2, dilute, propionyl-2-mer radical or present Methyl; R4 is 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 4-fluorophenyl, 3-methylphenyl or 3-methyl-4-fluorophenyl; R6 is _ Nri8r]9, wherein r1S is hydrogen and R19 is -C(0)r23, wherein R23 is methyl, ethyl, isopropyl, bis-8-amino, cyclobutyl(-)methylcyclopropyl; r7 is hydrogen, Gas, fluorine or methane; iR8 is hydrogen, gas or methyl. For example, the method of the present invention can use a compound of the formula 1 (h), wherein: is hydrogen, a sulphate, a cerebral palsy 4, a rhyme, a 4th generation, a Cn4 alkyl group, and a c, 4 _ generation. The alkyl group is optionally substituted by Cm morphoxy or Cm 33 201020252 haloalkoxy; R 2 is hydrogen, halogen 'hydroxy, -NH-Cu alkyl, -nH-Cm haloalkyl, -Nfw alkyl)-C| -4 alkyl, -N(Cl4haloalkane)-Ci4 alkyl, '(Cm alkyl)-Ci-4haloalkyl, -Νβ]-4haloalkyl)-(:,-4haloalkyl, -NH-C3 .6 cycloalkyl, -NH-C3_6 functional cycloalkyl; R is 虱' Ci-4 alkyl, 〇1-4 halogenated alkyl, C2-4 dilute, C2-4 haloalkenyl, C2 .4 alkynyl, 〇2·4 haloalkynyl, wherein alkyl, haloalkyl, alkenyl, _alkenyl, alkynyl and functional alkynyl are optionally selected from cyano, C^ alkoxy And a substituent substituted by a C, ·4 haloalkoxy group, or R3 is a benzoic acid which is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, cyano, Cl-4 alkoxy and Ci-4 haloalkoxy R4 is a phenyl group optionally substituted by 1-3 halogen atoms; R6 is hydrogen, halogen, hydroxy, CU4 alkoxy, (^. 4 haloalkane) Oxygen, -ΝΗ2, -NH-Ch, and -NH-Cu haloalkyl, wherein the alkyl and haloalkyl are optionally substituted by a hydroxy or Cw alkoxy group (which may be substituted by a hydroxy group), or R6 is -NH-qCO-Cu alkyl, -NH-CCCO-Cw haloalkyl, -NH-C(0)-C3-6 cycloalkyl, _NH-C(0)-C3.6 i cycloalkyl , -NH-C(0)-C2_4 alkenyl, NH-C(0)-C2.4 i alkenyl, -nh-c(o)-c2_4 alkynyl or -nh-c(o)-c2. 4 _ alkynyl; R 7 is hydrogen or halogen; R 8 is nitrogen or halogen. For example, the method of the invention may use a compound of formula 1 (h), wherein: R 1 is hydrogen, -NH-Cw, and cumane The base system is optionally substituted by a methoxy group; 34 201020252 φ R is hydrogen or _ 素; R is gas, Ci-4 alkyl, Ci/I, pull·&amp; 3-4 homing, C3-4 alkynyl Wherein the Cm alkyl group is optionally substituted by a cyano group or a methoxy group; R is a phenyl group optionally substituted with 1 to 3 atomic atoms; R6 is hydrogen, -NH-C, .4 alkyl, wherein The alkyl group is optionally substituted by a hydroxy group or a C1-alkoxy group (which may be substituted by a hydroxy group), or R6 is a -NH-C(〇)-Ci_4 alkyl group, nh-c(o)-c3_4 naphthenic acid a group, -NH-C(0)-C3_4, or -nh-c(o)-c2-4 alkynyl; _ 7 R is hydrogen or 13⁄4; R8 is hydrogen or 13⁄4. The process of the invention may use a compound of formula (Ii): R4 R7

Wherein R1, H2, R3, r4, R6 and R7 are as defined above for formula (Ih), in any combination thereof. The process of the invention may use a compound of formula (Ij):

35 201020252 where R2, R3, R4, r7 and r8 are defined in any combination. In the above formula (Ih), the method of the present invention can be used (π〇 compound:

'R, R, r7 and R8 are as defined above for formula (Ih) , in any combination thereof. In a specific embodiment, the method of the invention uses a compound of formula (II):

among them

〇, 〇2, and 〇3/(壬—^ . , , where N is and G1, ^2, and G3 are both CR8, CR1哎CR2, estimated β丄],

Each 2 4 ΙΚ makes the waiter Gi not Ν, G1 is CR ▲G is not N, 1 , ?, when G3 is not N, G3 is CR2 and is better, in any combination of the following: R is hydrogen , halogen or Cm alkyl; R 2 is hydrogen, halogen or Cl 4 alkyl; R 3 is hydrogen, optionally substituted CV 6 alkyl, optionally substituted 36 201020252 case substituted C 2 · alkynyl, optionally Substituted base); 疋 and more preferably _ or alkoxy (for example, -o-c&quot;alkyl, as appropriate: the substituted aryl group', for example, optionally substituted benzene J The substituent is as defined above and is more preferred; and RI9 is; ^SR18 or Guan, 9, wherein W is ammonia or Cl.4, and R23 is C|·4, _C (S) R23 or {(0) only 23, meaning; base 'optionally selected as the above, R is 虱, 素素 or cU4 院基;

k is ammonia, Jb: * V Nansu or CN4 alkyl. Or gas is any combination of the following: Ri is hydrogen, methyl, ethylmorphyl-〇-c-yl, ethyl or chloro; R3 is hydrogen, halo-Cm alkyl, in other words Hydrogen, radical, Cl.4 alkyl, C2.4 dilute or C2·4, especially agglomerate; R4 is phase/ethylidene, methoxymethyl, propyl-1,2. dilute or propyl _2_ 素素, such as fluoro substituted phenyl 'optionally selected as 1 methoxy small chlorine or _NRl8R19, its &quot;18 is nitrogen and the heart is the basis, specific = base, C ( S) R23 or, R23, u23 is a k group; R7 is hydrogen, °A', 1-methylethyl, K-dimethylethyl or 3-mercaptopropene. Earth, ethyl or chlorine; and Han 8 is hydrogen, mercapto, ethyl or the method of the invention can use the compound of formula (Im) · 37 201020252

In the definition, it is the second form and the above is about the form of the formula (8). The process of the invention can be carried out using a compound of formula (In):

As defined by II, the complex R, R, R and R are as described above for the formula, in any combination. Process 1 of the invention can be used with a compound of formula (Ιο):

In the righteousness, the enemy::~^ and the system are as defined above for the formula (7), in any combination, for use in the present invention丄

Shown in II and III. Examples of compounds in bismuth are listed below. 38 201020252 Table ι-(Ik) compounds

No. R1 R3 R4 R6 R7 R8 Melting point (°c&gt; 1 Η Φ Φ +Η +Η 2 II Ν-V Η V- ΗΟ +Η B -fH p^' +Η _|_Η 4 +Η +Η 245-247 5 +H k φ +Η +Η 6 Less φ +Η +Η 7 Η ^-H φ +Η +Η +Η 8 ΝΛ -IH φ -fH +Η +Η 9 φ ΗΝ^ ΟΗ +Η -fH 39 201020252 No. R1 R3 R4 R6 R8 Melting point PC} 10 Φ ΗΝ~λ ^-OH +H +H 11 -lH Φ HN-\, +H +H 12 +H -fH +H ^-H 92-95 13 9 ) + H +H 142-144 14 Η P_ X OH +H +H 242-244 15 9 NH I +H 16 9 NH 卞170172 17 +H +H P_ 0 ) +H +H 166-168 18 +H 9. X Nh2 multi-H +H 248-250

40 201020252

No. R1 R3 R4 R6 R7 R8 Melting point (°C) 19 9 卞+Η +Η 174-176 20 9 _|_Η ·-^—Η 25^252 21 +H 9 •Η* ΝΗ I +Η 190192 22 +H 9 ΝΗ I +Η -|-Η 250-252 23 夕 P. νη2 +Η +Η 206-208 24 9' Ή1 ΝΗ, -|~Ή 25 夕9 +Η 196-198 26 夕9 Ή* ΝΗ +Η +Η 188-190 27 +H 夕9 Η1 ΝΗ I +Η -fH 182-184 41 201020252 No. R1 R3 R4 R6 R7 R8 Melting point (ec) 28 夕9 \h 卞16Φ166 29 9 Ή* ΝΗ +Η 168-170 30 +H 9 ΝΗ -fH 152-154 31 +H 9' ΝΗ 卞+Η +Η 32 +H 9 -Η1 ΝΗ % +Η 172-174 33 +H 夕9 Η+Η +Η 186-188 34 + H 9 gas Η \ +Η +Η 218-220 35 9 gas Η -^-Η -Ι-Η 182-184 36 +H +HF +Η +Η 42 201020252

No. R1 R3 R4 R6 R7 R8 Melting point (°c) 37 F % -lH 38 F % -fH 224-226 39 F ^ _J m~^y +H +H 228-2B0 40 -IH Φ m2 +H 224-226 41 •H* NH A +H -f~H 42 -IH Ip +H +H —H 225-227 43 P_ +H +H 85-87 44 P. +H +H +H 132-135 45 -u P .+H +H +H 122-125 43 201020252 HPLC-MS or MS data for some of the compounds in Table la-Table I

Compound No. Retention Time (minutes) Mass (ES+) Method 34 5.93 460 B 43 3.58 328 B 49 5.41 398 B 15 5.93 460[M+1T C 24 3.58 328[Μ+Π C 36 3.49 362ΓΜ+11 D 37 3.64 374[ M+11 D 41 3.83 388ΓΜ+1] D Method: For details, refer to Method A, Method B, and Method in the “Examples”.

C and Method D Table II - Compound of formula (Ii) 201020252

No. R2 R3 R4 R6 R7 R8 Hyun point i°q 1 -fH Φ Ίή Card H 2 夕Φ -^Ή Today H 3 -ftH F Φ -fH 4 Φ Today H 5 -4h -fH 9 Today H iHH 166-168 6 v|a, Cl -fH P &quot;Ιή -fH 230-232 7 v(a. Cl P -fH -fH 107-109 45 201020252 No. R2 R3 R4 R6 R7 R8 Melting point (°C&gt; 8 •«t Cl P +H Ί-Η 160-165 9 Cl 1 P ·% +H Hand H 148-150 10 \|v P +H +H 128-130 11 i· s OH +H Ψ , P +HA +H +H &gt;250 12 +H \ P' +H +H +H 122-124 13 V 〆\ S| NP +H -fH +H 160-162 14 vj/VA -fH P +H +H +H &gt;250 IS vj/v NH Y Λ^/VHP +H +H +H 232-234 46 201020252 No. R2 R3 R4 RS R7 RS Melting point rc) 16 NH cf Η Ρ 十Η An-Η 多.Η &gt;2:£0 Table III - Compounds of formula (Ii)

No. R1 R2 R3 R4 R6 R7 1 +H +H —^~H 2 +H +H Nh +H 3 —^~H Hand H r λ +H +H 4 +H +H NN % Hand H -fH in another In one aspect, the invention provides a compound of formula (I) as defined above, wherein the conditions are: (When G1 is CR8, G2 is CR1, G3 is N, X1 is CH, X2 47 201020252 is CR, and "r6 is a material, then r4 is not 4 fluorophenyl; and * (11) formula (I) is not: 7-phenyl-6-(acridin-4)- 5H_D ratio [3] , 2_c] tillage; 7-phenyl-6-(pyridine-4-yl)_5H_pyrrolo[3,2 d]pyrimidine; 7-phenyl-6-(acridine_4_yl)_5Η_πΛ [2,3_b]n ratio tillage; 7-0-gas phenyl)-6-[2_(2-methylthioethylamino)_4_〇pyridinyl]_5H_〇比略和[2,3 - b]. Compartment; 7-(3-indolyl)-6-(2-azeridin-4-yl)-5H-n than s-[2,3-b]. Specific tillage; or ❿ 7 -(4-fluorophenyl)_6_(σ ratio 44·yl)-511-0 piroxime [3,2-&lt;1]° σ. The present invention also provides a formula as defined above ( A compound of the formula Ia, wherein the compound of the formula (la) is not: 7-phenyl-6-(acridin-4-yl)-5Η·pyrrolo[3,2_c]. A compound of formula (lb) as defined above is also provided, with the proviso that the compound of formula (Ib) is not: 7-phenyl-6-(acridin-4-yl)_511_pyrrolo[3,2_d] Pyrimidine; or fluorophenyl)·6_(°-pyridin-4-yl)-511-°pyrho[3,2-d]pyrimidine. ^ The present invention also provides a compound of formula (Ic) as defined above, The limiting conditions are as follows: (1) When X1 is CH, X2 is CR5, and R5 and R6 are both Η, then R4 is not 4-fluorophenyl; and (Formula C Ic) is not: 7_phenyl- 6_(.bipyridyl-cardiyl)-5H-»pyrho[2,3-b]° ratio tillage; 7-(3-aza base)_6_[2-(2-mercaptothioethylamino) -4-pyridyl]-5H-. Compared with 48 201020252 0 each [2,3-b]. than the brown; or tillage. II) 7 (3 gas base) _6_ (2 · gas bite _4 base) _5h. The ratio of b to each [n the present invention also provides the formula (Id) as defined above, (compound, the restrictions are: (not

(!) When G1 is CR8, G2 is CR1, g3 is N 4-fluorophenyl; and Ί R (/(Id), (Ih) or (η) compound is not:

7_本基Mm-基)-5H- and [3,2-c] towering; 7-phenyl-6-to-bit _4_yl)_511_吼 并[3,2_d]. Methylpyridine; phenyl·6·(pyridine-4-yl)-5H-pyrrolo[2,3_b]pyrazine;

7-(3-乳基基)·6_[2_(2_methylthioethylamino)n-decyl-[2,3-b]pyrazine; J, (chlorophenyl)~6_(2·chlorine Pyridine·4_yl)-·5Η-. More than [2,3_b]Dttj she or · split; (fluorophenyl)-6-(pyridin-4-yl)-5H-pyrrolo[3,2-d]pyrimidine. The present invention also provides a formula as defined above (1〇, ((1) or a compound 'with the limitation that the compound of the formula (Ie), (Ii) or (im) is not:) 7-phenyl-6-(pyridine_4 _基)_5H_d is more than [3,2_c] 嗒耕. ', ' . The invention also provides a formula (if), (丨 )) as defined above: its restriction condition is (former (8) or (h) The compound is not ^) 7_phenyl_6 decapyridyl·4_kibido[3,2-d] citrate; or '',, 'fluorophenyl)_6 pyridine-cardiyl)_5H ♦ Each [3, 2 d (tetra) pyridine. The present invention also provides a compound of the formula (Ig), (Ik) or ίτ as defined above, the limitation of which is: 0) 49 201020252 (i) R4 is not 4-fluorophenyl; and (Η) formula (Ig) The compound of (Ik) or (Ιο) is not: 7-phenyl-6-(pyridin-4-yl)-5Η-. Bisino[2,3-b]pyrazine; 7-(3-(phenyl)-6-[2-(2-mercaptothioethylamino)_4_acridinyl]pyrrolo[2, 3-b]. Specific tillage; or 7-(3-phenylphenyl)-6-(2-gas.pyridin-4-yl)·5Η-吼 并[2,3_b]pyrazine. In general, the present invention provides Formula (I), (Ia), (Ib), (Ic), (id), (Ie)^(If). (lg). (ih). (Ii). (Ij )&gt;(Ik)^(I1)^(im)^in)

And a compound of any of (1), wherein the compound is not disclosed by w〇 99/20624. For the avoidance of doubt, the compounds listed above are named according to the scheme described on pages 17 and 18 of 〇 99/20624. W〇 99/20624 is incorporated herein by reference. The invention also provides formula (I), (la), (Ib), (Ic), (Id), (Ie), (if), (ig), (ih), (h), (I:j) a compound of any of (Ik), (n), ((4), (In), and (Ιο), wherein, when present: &amp;, &amp;, G3, X1, X2, R|, R2 u, R5, r7, r8, R丨, Rll, Rl2

R&quot;, Rm, Ri5, Ri6, r17, r20, r21, r22, r23, r2^r2 are as defined above for formula (I) in any combination thereof, and in any combination of the following: R6 is: ( i) a trans- or ethoxy group, (ii) as appropriate, substituted, ^, ^ ^ ^ ' &amp; square (eg, as the case may be substituted), as appropriate r Al , ^ ^ ^ beach square 丞C, for example, a heterocyclic group substituted according to the case), optionally substituted naphthene, f Λ丨, ^ Fu Yi also &amp; (for example, C3-6 ring substituted as appropriate 50 201020252

a thiol group (e.g., optionally substituted c" and a heterocyclic ring formed as defined above as R5-C(0)0RI8, Nr1 wherein R is optionally substituted (e.g., NH2) or -N = CR20 The substituent is preferably as defined above in all cases, R6 is _Nri8r19, 4HC(0)R23' wherein r23 is preferably cyclopropyl or cyclobutyl. For example -NHR19. Best, R6 is C 1 · 4 alkyl, such as ethyl, isopropyl, R丨8 is: (i) hydrogen, (π) Cw alkyl, optionally substituted alkenyl or optionally substituted C2_6 alkynyl, (iii a heterocyclic ring (such as a 5- or 6-membered heterocyclic ring), or (i〇-C(〇)R23, 4(0)0^3, s(〇)2R23 or _c() 〇)nr23r24; wherein the substituents selected as appropriate are, in all cases, as defined above and more preferably selected from the group consisting of hydroxyl, cyano, halogen and alkoxy (eg alkyl). Μ Better' R18 is hydrogen, C, _4 alkyl, c2-4 alkenyl or C2.4 alkynyl. You

Ri8 is oxime, ethyl, isopropyl, propan-2-yl, propan-2-free or butynyl. '2· R丨9 is: (i) Hydrogen, 51 201020252 (11) c丨·6 alkyl, as appropriate, substituted C2.6 block, Gezhi^ women base or depending on the situation (lh) A substituted aryl group (in the case of hydrazine, optionally substituted heteroaryl (e.g., m group), optionally substituted cycloalkyl (e.g., optionally substituted alkyl) ), that is, 1 (four)-like ring county (for example, (10) substituted / cycloalkenyl) or optionally substituted heterocyclic (for example, 3 member _6 ^ substituted heterocyclic base) or as appropriate The complex formed with r18 (for example, a 5-member or 6-membered heterocyclic ring), or (iv) -C(S)r23, _c(〇)r23, _c(〇)〇r23, -C(0)NR23R24, ^ Wherein the substituents selected as appropriate are in all cases as defined above and more preferably selected from the group consisting of a thiol group, a cyano group, a hydroxyl group, an alkoxy group (e.g., a decyl group), a benzyl group (e.g., 'keki group), a ring. Alkenyl (e.g., C "cyclo 4 dilute") and heterocycloalkyl (e.g., 3 member-6 heterocyclic); more preferably, R19 is hydrogen, _c(s)r23 ' _c(0)r23 4_c(〇)〇 R23 or Cl-4 alkyl. The best 'Rl9 is hydrogen, isobutyl, -C(〇)R23 or _C( 〇R23. The invention also provides formula (I), (Ia), (Ib), (IC), (Id), (Ie), (If), (Ig), (Ih), (11), ( a compound of any of Ij), (Ik), (II), (I), (In), and (), wherein, when present: Gi, G2, G3, 〇

X1, X: R13 ' R R|, R2, r/

R5 ^ R6 ' R7 ' R ' R 10 R&quot;, R1 R1 R1

R17, R18, R 19

R 20 R:

R 22

R 23 R24 and R25 are as defined in P', and are defined in the formula (I) in any combination thereof: 52 201020252 R3 is: (i) hydroxyl group, (8) H brother substituted C丨·6 yard base, depending on the situation Substituted gamma or optionally substituted c2.6 alkynyl, ali, optionally substituted cycloalkyl, for example, substituted C3_6 3 lityl, or (lv) _C(〇) R12, _0RU, _c(〇)〇rI2, _ -S(0)2R12;

The substituents selected as appropriate are, as defined above, in all cases and are more preferably selected from the group consisting of cyano, (iv), thiol, Cu4, C24 alkenyl, alkoxy (eg, -〇_C, ·4). An alkyl group, optionally substituted by an alkoxy group (e.g., an alkyl group) or a fluorenyl group (e.g., _(0)C_Cld alkyl), a cycloalkyl group (Example 3-6 cycloalkyl group), a lanyl group (e.g., C34 cycloalkenyl), heterocycloalkyl (for example, 3 member-6 membered heterocycloalkyl), aryl (for example, phenyl), heteroaryl (for example, heterophenyl), oxime 2, dicalcium ruthenium, _C(〇)R and _C(〇)〇R (wherein R is hydrogen, methyl or ethyl). More preferably, R3 is a hydroxyl group, _C(〇) RI2, _〇Rl2, _c(〇)〇r|2, small c(0)Rl2, _S(0)2Rl2, optionally substituted Ci-6 alkyl group, Optionally substituted C2-6 alkenyl, optionally substituted C2 6 alkynyl, optionally substituted cycloalkyl (eg, optionally substituted C: 3·6 cycloalkyl). Most preferably, R3 is cyanoguanidino, aminoethyl, aminopropyl, vinyl, prop-2-enyl, prop-2-ynyl, propane-1,2-dienyl, methoxy Methyl, 2-fluoromethyl, 2-fluoroethyl, -OCH2CM:H, -〇CH2〇CH3, -OCH2CN, -OCH(CH3)CN, -〇〇:Η2(:Ιί=(:Η2 or benzene Methyl β 53 201020252 In another aspect, the invention relates to a method of preparing a compound of the invention (eg, a compound of formula (I)) as defined according to any of the above aspects, comprising: a) (F) compound cyclization

G

Wherein G1, G2 'G3, R1, R2, R4 and R8 are as defined for formula (I), X is halogen, and R is a group of the formula:

且 and X1, X2, R6 and R7 are as defined for formula (I), and the formula (G) is obtained:

R (G) 54 201020252 and optionally derivatized with a group r3 at the position of the secondary amine, as defined by formula (1); preferably, the derivatization is by spot R; LG The reaction (wherein the leaving group is a burning group), or by reacting with RC〇_LG (which +Rl2 is as defined for formula (1) and (10) is a leaving group); or b) making formula (K)丫丫u bow

R (Κ) -一^ Iffj 义 'R is as defined above' and LG is a leaving group, which reacts with a compound of the formula R4-B(OH)2, straight 4 of the formula R as in the formula (I) Defined to give a compound of formula (G) as defined above,

And optionally, derivatized with a group R3 at the position of the secondary amine, wherein the V system is as defined for the formula (1); preferably, the derivatization is by reacting with R3-LG (its t LGI is gone) And r3 is a burnt base), or by virtual

Ri2C0-LG reaction (wherein t R12 is as defined for formula (1) and [^ is a leaving group); or 'c) is a compound of formula (S) 55 201020252 wherein

R

IV is defined by formula (I), and R is as defined above, opposite to the compound of formula R-LG, having a dry R system as defined and LG being a leaving group, to give a compound of formula (τ), work enthalpy

Suitable leaving groups mentioned in this technique are, for example, sulfamate, triflate or methane.

As (a), (b) and (c) are well known in the art and may be an acid S-based group. The process of the invention may comprise a salt of the formula. (I) conversion of a compound to its ruthenium oxide

I. The compounds of the invention encompass all possible combinations of substituents as defined herein.

Of course, the skilled person will appreciate that the compounds of the invention can be prepared by a variety of other methods. 56 201020252 Compounds of the invention and the compounds used in the process of the invention are prepared by the reaction schemes and methods detailed below. Starting materials which can be used, for example, by the compounds, are commercially available from the general commercial suppliers and are prepared by the procedures known to those skilled in the art. The starting materials are purified by prior art methods according to the following procedures: distillation and filtration. , 'D a曰, the recommended procedure is listed below to illustrate the preparation of the general formula 丨 compound Ο, which can be modified by those skilled in the art to obtain a compound. Detailed procedures for the various steps detailed in the text can be found in the following references: /. chest · cw 2〇〇3, 46, 47〇2 4713, such as ^ s, 2〇, 3121_3125; such as ^ 2〇 80 '8087-8090 〇 The compounds of formula (I) listed above and listed in the above tables can be prepared according to the procedure outlined in Scheme 1 of Process 1:

R4-CH2CN

B

Process 1

Where R is: 57 201020252

And Χ and X2, Ri to R8 are as defined above, and hydrazine is halogen. The 5th substance can be obtained by reacting the ester of the formula A with the acetonitrile derivative of the formula B in a suitable alcohol solvent in the presence of, for example, sodium decoxide or a third butanol. CAem. 2003, 46, 4702-4713).

The compound of the formula A is generally commercially available, but can also be prepared by subjecting the corresponding acid, nitrile or methyl derivative to esterification, hydrolysis or oxidation, respectively, by the prior art. Formula 3 compounds such as phenylacetonitrile, 4-fluorophenylacetonitrile or % methyl phenylacetonitrile and related compounds are commercially available. The acid treatment of a compound of formula C in a palatable aqueous acid solution (e.g., hydrobromic acid) produces hydrolysis and decarboxylation to provide a compound of formula D. And condensing with a heterocyclic ring to form an enamine of formula F,

Wherein X is a halogen 'such as a desert', a gas, or an iodine. The reaction can be carried out in the presence of a catalytic amount of an acid such as p-toluenesulfonate in an aromatic solvent such as Benzene or Bis. The quaternary quinone-imine equilibrium form of gamma 5 can be separated under prior art purification materials such as chromatography. ^ A heterocyclic ring of hydrazine (such as 3_gas, _4_ylamine or 3_methane) is prepared by a known method. For example, the corresponding nitro derivative (2042) is recovered. Such as the other - (see J. can be prepared according to the procedure reported in / 〇 W / ^ a / 58 201020252 CAembir less 1964, 1 (5), 247-50. The enamine F in the tertiary amine In the presence of a base such as DABCO and a palladium catalyst such as palladium(II) acetate or dichlorobis(triphenylphosphine)palladium(II) in an inert solvent such as dimercaptoamine or dimercaptoacetamide Centralization, obtaining the diterpene of formula G (5H-pyrrolo[3,2-c] sorghum, 5H-pyrrolo[3,2-d] pyrimidine or 5H-n ratio slightly [2, 3-b]0 than well) (see J. CAem. 1997, 62, 2676-2677) ° A compound of formula η (wherein R3 is not hydrogen) can be obtained by burning or deuteration of a compound of formula G. An alkylating agent of the formula R3-Y (where γ is in the presence of a base such as sodium hydride or lithium hexyl quinazoline in an aprotic solvent such as dimethylformamide or tetrahydrofuran) The leaving group, such as a halogen, a difluoromethanesulfonate group, a mesylate group, and the like, can also be achieved by, for example, hydrogenation in the presence of a hydrating agent such as R3COX (wherein hydrazine is a halogen) Alkali storage of sodium or hexamethylene diazoxide In the following, it is deuterated in an aprotic solvent such as dimethylguanamine or tetrahydrofuran to obtain a compound of formula G. Scheme 2 describes an alternative method for preparing a compound of formula (1.): Scheme 2 59 201020252

The compound of formula J can be obtained by one-step condensation-cyclization of a compound of formula E with a compound of formula I. Reaction in a closed vessel 'under an inert atmosphere, © in an inert solvent (such as dimethylformamide or dimethylformamide), in a base (such as potassium or potassium carbonate) dehydrating agent (such as magnesium sulfate) Or sodium sulphate and palladium catalyst (preferably (di-t-butylphosphino) palladium) in the presence of 4 see CAem. /ni_ £d· 2004, 4526-4528 ) 〇 can be in bromine or N-brominated Positional selectivity of compounds of formula j in the presence of dimethylene imine in a solvent such as a gasification gorge or DMF

Bromination by (regl〇SeleCtiVely) gives a compound of the formula κ (see (10) 乂 1982, 1096). It can be obtained under the conditions of Suzuki and Coupling (Suzu]d Q coupHng) (see c/2(4)·c〇Ww 1979,866), under heat or microwave conditions, in the formula r4b(oh)2 (where R4 is such as The compound of formula G is obtained by further processing the compound of formula κ in the presence of boric acid as defined previously. You can then follow the above process! The procedure described yields 4 conjugates. &lt; Scheme 3 describes an alternative method of preparing a compound of formula (1). 60 201020252

Me n

E

R

M

R M Process 3

R4-B(OH)2

o

R

PG

R4-B(〇h)2

By protecting the corresponding heterocyclic ring E PG as a protecting group, such as a methicone and a servant L compound (wherein the toluene sulfonic acid S group and the like), the bentonite, the stone "", "G" (see PrGteet]Ve g乡in

Greene and, ts, 4th edition, Wiley (4) (10)). The compound of formula L can be coupled with the compound of formula m under the conditions of the head coupling (S_gashlra coupllng e〇nditi〇n) (see Addition, (8) 627-630) and then in an inert solvent such as di-methane. Treatment with angstrom 'direct iodine cyclization and formation of ruthenium (see 2〇〇4, 6(6) 1037-1040) 〇 can be achieved by making the parent halogenated compound in the hoe condition (see Nthesis, 1980, (8) 627 -63 0) is reacted with trimethyldecyl acetylene, and then the protecting group trimethylsulfonyl group is removed under the conditions of base 61 201020252 to obtain a hydrazine compound. The hydrazine compound can also be prepared from the parent aldehyde under the Corey-Fuchs reaction condition (see 7^. J972, (36) 3769). The hydrazine compound can be obtained by treating hydrazine in the presence of acid scavenging under the same conditions as described for κ in Scheme 2 above.

Depending on the nature of the visual protecting group, a compound of formula G can be obtained by removal of a protecting group of a hydrazine compound under prior art methods. For example, the acetic acid S group as a protecting group can be removed under acidic conditions (such as Ηα), such as L_. It should be noted that a weak protecting group can be removed during the reaction to yield a formula N or a hydrazine compound. Should also pay attention to the beginning of preparation? (} can be the same as R3' so there may be no need to remove the protecting group step. The compound can be obtained according to the procedure described above in Scheme 1. It is also possible to make the amine base E and the compound of formula M in (4) conditions. The next reaction' is then cyclized under the test condition (ΝΕν K0H) (eg £2〇〇7)

4/, 695 1 · 6593 f) and directly treating the aminoheterocyclic oxime in two steps to obtain the formula ". The remainder of the process can be as described previously. Scheme 4 describes an alternative method for preparing a compound of formula (1) wherein r2 is 〇Ri2 as previously described: Scheme 4 62 201020252

Then, in the presence of the osmium-based heterocyclic compound potassium tributate, in the presence of aprotic, t, to obtain a compound of the formula Q, which is also a U compound (in which a substance such as gas or desert) can be obtained from the market. The purchase can be made by a known method. For example, such as 4_gas-&quot;oxygen

Let the formula of formula D (such as the first test (such as sodium hydride or the first agent (such as dimethylformamide can exist in the form of its enol. 5-nitro+ and 3_chloro.2_sulfoindole ratio The compound of the well can be described commercially. For the preparation of the compound of formula P, those skilled in the art can follow the example of preparation of pyridazyne, such as 仏 仏 (9), 〇e 1967, 49 244-245 Alternatively, the compound of formula q can be selectively reduced at the nitro position under alternative conditions to produce a 1-hydroxy fused pyrrole of formula S. For example, under the condition of CBechamp condition, in the presence of iron, The compound of formula Q is treated in an aqueous acid medium to give a compound of formula s. Under these conditions, it can also be formed. The fully reduced form of ruthenium can also be pressurized or not in the presence of hydrogen under catalytic hydrogenation conditions. Pressing, using a catalyst (such as free/carbon) to treat the compound of formula Q in an alcohol solvent such as ethanol in 63 201020252. The compound of formula S can then be treated under the same conditions as described for G in Scheme 1, yielding T compound, wherein R12 is as previously described. 5 depicts an alternative method of preparing compounds of formula (I), wherein R6 is not hydrogen. Scheme 5

For this procedure, it can be catalyzed by acid in sterol or in a suitable trialkyl phthalate such as trimethyl orthoformate (for the preparation of dimethyl acetal) (eg 2010 20252) Treatment of the corresponding aldehyde in the presence of sulfuric acid)

. The ft 5 &amp; , , L , as previously described, is converted to its condensed v. Compounds of formula U are commercially available, for example, 4_pyridine furfural, hydrazine nitro-isolated, and 3-gas {pyridylfurfural, but can also be prepared by prior art methods, for example, by methylation. The material was the starting material and was prepared using an oxidation procedure (see = Q State 1993, 46(7) 987_993) and by reduction of the corresponding energy: The compound of formula U can also be prepared from a halogen-metal or a metal exchange by a halogen-metal or a metal exchange followed by a suitable electrophile such as dimethylguanamine (see Office), Heart 1999 , 3〇63丄]). It can be used in an aprotic solvent (such as four gas or screaming), preferably at a low level: under a suitable test (such as n-butyl, sodium nitride or six) Methyl bismuth i burning i) treating a compound of formula V, followed by a compound of formula w (wherein 4 X is a leaving group such as a halogen (gas, bromine or iodine) or mesylate group and R 4 is as previously described The anion is treated to obtain a compound of formula 2. The compound of formula W is generally commercially available, for example 4-fluorobenzyl, 3-mercaptobenzyl or benzyl bromide, but may also be prepared by prior art methods. For example, it can be used in the presence of a peroxygen gas in a solvent such as dichloromethane in the presence of a catalyst such as methyl antimony trioxide (see, for example, 37(6), 805-predicate). Or in the presence of a hydrogen peroxide-urea complex in a solvent such as dichloromethane (see to brew r 1992, 125(8), 196 5. 1966), oxidizing a compound of formula Z to produce a compound of formula A. A compound of formula a can be produced by treating a compound of formula AA with an amine-based heterocyclic ring of formula E as previously described for the preparation of F in Scheme 1. Or 65 201020252

' can be reversed by making the compound of formula AA and formula E lower at the temperature at which the alcohol formed is steamed = (see Office 1993, 12, 1227_1229). As mentioned previously, the hydrazine compound amine and the dilute amine are present, which can also be prepared, for example, by chromatographic isomerization (sub-inhibition of the hydrazine compound under conditions described for the formation of G)哚AC. The compound K can be used in the prior art method (the gasification of the substituted "gasification" in 1QQ4 em· and Pharm' Bull. ❹ Π.:?:1) To prepare the formula AD σ (/, where X is a halogen, such as chlorine or bromine). Can be - by the formula in the amine or amine, (9) catalyst (such as - acetic acid Is), ligand (Bee ^π γ Λ...c such as XantPh〇s®), in the presence of a base (such as carbonic acid = stone anaerobic), in an aprotic solvent (such as di- or u, u-wave conditions) Valer (B-) amination or guanidation to prepare compounds of formula ae (see ❹ (4) Shan, . 2001, 3 (21) 3417-3419). Also from AD by direct use of amines such as benzylamine Treatment with heat or microwave conditions, followed by treatment with a strong acid such as sulfuric acid to produce a compound of formula AE (wherein Han 6 is a simple 2) to prepare a compound of the formula 可由. A suitable non-nucleophilic test (such as a ratio) in a solvent of formamide or tetrahydroanthracene and a oximation agent (such as R, X, which makes hydrazine chlorine or morphine and r2. as previously described) The intermediate is further processed. It can also be treated under the same conditions with a burning agent such as rI8-x', its tX4 leaving group, such as a genomic element or a phthalic acid 66 201020252 ester group. Or deuteration will provide a compound as previously described under the same conditions, wherein R6 is nr18r19. Can be as Sc-ce 2〇〇5, 15, 285_387 (Ge〇rg

The compound of formula AE (wherein R6 is not an amine and a guanamine) is prepared directly by treatment of a compound of formula AC with an activator followed by a nucleophile as described in the review by Thiem Vedag. For example, if R6 is a cyano group, it can be activated in an aprotic solvent such as dimercaptocaramine or tetrahydrofuran in the presence of a cyano source such as tridecyldecane cyanide. Agent (such as styrene-brewed chlorine) © Processed AC compound (see · /_ Org. CAem, I983, 48, 1375-1377). 6 The existing branching method further modifies the S AE compound (which is a cyano group) to produce all possible derivatives of the cyano group: for example, reduction to an acid or an ester, reduction to a decylamine or reduction of dizziness, or amine-by alkyl group Or aryl Grignard reagent (Grignard) produces _ for cyano addition. The oxime compound can be prepared from the compound of formula AD according to the procedure described in Scheme 1 for the preparation of a compound of formula η from a compound of formula G. The compound of the formula A G can be produced from the compound of the formula AE according to the method for preparing the intrusion u and the s. A method for preparing a compound of the formula AE from a compound of the formula AD can also be included, and a compound of the formula AG can be prepared from the compound of the formula. The compound of the formula AF can be prepared from the compound of the formula AE by the treatment of:::: to make the bite oxidize the gas as described in the formula AA compound - such as the self-formed AD compound floc preparation AE compound φ about the bow into the R6, direct reaction to introduce r7 "Do not Zhongguan, bow 丨 67 201020252

At- can also be introduced by the method described in relation to the introduction of R6 in the preparation of a compound of the formula from a compound of the formula AC to introduce R7 ° according to the process described in Scheme 1 for the preparation of a compound of the formula: A hydrazine compound of the formula is prepared. Other steps not disclosed in Scheme 5 can be achieved from the AC, AD, Al, AE, AF, AG, and AH compounds. Such reactions (for example, cyclization between 3 or with 〜1) allow R1 to be introduced into the broad formula 裎6 to describe the preparation formula (n is a compound of R ( (wherein χ © for example, a compound of formula (IC), where G1, G 'G3 Χ R, R4, R6, nm "G, R, R2, as defined by equation (1)).

(Ic) R6

201020252 A compound of formula AL can be prepared by treating a pyrimidine of formula AJ (wherein x is hydrazine, such as a fill, chlorine or argyr and y is as previously described) in the presence of a suitable base to achieve a metalloprostol exchange. A positive τ-based clock or a second butyl group may be used in an aprotic solvent such as tetrahydroculphonate, preferably at a low temperature. The hydrazine-based vapor of the hydrazine can be reacted with a pyrimidine anion previously formed to give a compound of formula AL. The compound of the formula AJ is commercially available, such as 4? iodo-2-methylthio-pyrimidine, or can be obtained by prior art methods (see, for example, Chem., 2 ❹ 42(2), 311_313). The hydrazine compound is usually commercially available, for example, stupid oxime, m-phenyl acetophenone or 4-fluorostyrene, but it can also be prepared from the corresponding acid. The ring of the hydrazine compound and the compound of the formula AL can be condensed under the conditions described for the formation of the compound F in the scheme, and then the obtained imine or enamine can be subjected to the conditions described in Scheme 1 for the formation of the compound G. To prepare a compound of the formula AM. Compound E is as previously described. ® Deuteration of the pyrimidine compound of the formula AM in the presence of an oxidizing agent such as meta-benzoic acid in a solvent such as a dichlorocarbazone to form an intermediate intermediate. This intermediate is further treated with an amine such as benzylamine, which is then treated in sulfuric acid to form a hydrazine compound wherein R6 is κι. Further processing, as described previously in Scheme 5 for the formation of compound AE, forms Ap, wherein R6 is as previously described. The compound of formula aN can be obtained by treating the compound of formula AM with the same procedure as previously described for the formation of a compound of formula H from a compound of formula G. 69 201020252 A compound of formula AO can be prepared from a compound of formula AN using methods previously described for the preparation of a compound of formula AP from a compound of the formula AM. The oxime compound can also be prepared by direct introduction of R3 at the indole ring of the compound of formula AP in accordance with the procedure previously described in Scheme 1 for the formation of a hydrazine compound from a compound of formula G. The amphibious A shoe preparations of the type Ε intermediates associated with the preparation of the compound of formula (li) or (lm) may be found in RecueH des Travaux Chimiques des Pays-Bas 1974, 93(8), 236-9; Yakugaku Zasshi, 1965 , 85(4), 344-52, Journal of Pharmaceutical Sciences 1963, 52(6), ❹ 539-41, and c/zew(4)r less le/ie&quot;, 2001, 54. The resulting compound E can then be converted to a compound of formula I(i) or I(m) according to the procedures previously described. The processes described above will enable those skilled in the art to understand the general conditions and techniques that can be used to obtain the compounds used in the present invention. If necessary, the groups R1 to R8 may be further modified to have a cyclic structure between Ri and R2, between R and R, between R2 and R3, between R3 and R5 or between R5 and R6. Compound. These further modification steps are routine procedures for those skilled in the art. In particular, those skilled in the art will appreciate that such modifications may be achieved by more than one step, including, for example, reduction, oxidation, coupling reactions (with or without catalyst), nucleophilic substitution, lactonization, endo-amidization And similar. As indicated above, it has now been found that when a fungicidally effective amount of a compound of formula I is applied to a plant or plant propagation material, it is useful for controlling phytopathogenic fungi. 70 201020252 Plant propagation material means planted seeds (fruit, tubers' bulbs, grains, etc.), all types of cutting strips and the like. Plant propagation materials may also include plants and seedlings to be transplanted after (4), soil Post-tooth or road-out in plants and/or plant propagation materials "controls are compounds such as inhibition (eg, selection of ^4 -" compound / Wang Yang) plants or plants = fungal infections. In contrast, (example == "compared to the case") the compound can be used in plants or plant growth materials to slow down fungal growth rates and/or reduce fungal growth materials. Selective inhibition of θ is now known as “selective inhibition” in plants or plant propagation materials. For example, (for example, with and without 兮: 情: 广... compound can be propagated in plants or plants Material reduction: the occurrence of true sputum infection and / or reduce the rate of fungus emergence. "In general, the control and / or prevention of compounds in the plant or plant propagation material can reduce the fungus in plants or plants. The ability to grow on plants or plant propagation material and / or reduce the rate of true and / or to any adjacent plants. The human '4 wood propagation noon can be biologically active, in terms of it can hinder the normal internality of the fungus Biochemistry. The second substance is toxic to the fungus. For example, it kills the fungus after contact, and "administers" the compound to the plant or plant propagation material means that the compound is in contact with the plant or plant propagation material to be treated. The phytopathogenic fungi of the present invention, the following types of soil. Not 1:: and the fungus ^^ 具 函. The whole fungus (Fungiimperf (10)) 71 201020252 . C such as Botrytis, Pyricularia ), Helminthosporium, Fusarium, Septoria 'Cercospora and Alternaria, Basidiomycetes (eg silk nucleus) Rhizoctonia, Hemileia, Puccinia, Ascomycetes (eg Venturia and Erysiphe, apple white peony) Species (p〇dosphaera), Monilinia, Uncinula and Pyrenophora, and Oomycetes (eg Phytophthora), Pythium, Plasmopara. In particular, the methods, compounds and compositions of the present invention are effective against Botrytis, Trichosporon, Fusarium, Cyanospora, Rhizoctonia genus, Powdery mildew, Phytophthora, Pythium and genus. Most particularly, the methods, compounds and compositions of the present invention are effective against Botrytis cinerea (5 〇 with less heart) 'Pythium sinensis (• less zae), Fusarium oxysporum (L. oxysporum) and S. cerevisiae () 'R. urticae (ii/n.zociow.a so/aW ) 'Puccinia sclerophylla (M. sinensis) (Pyrenophora teres, horse yam) Phytophthora z'n/esia/is, ultimate Pythium (wHmwm), and Plasmopara viticola. The methods, compounds, and compositions of the present invention are suitable for controlling a variety of plants and their propagation materials. The disease, the plants and their propagation materials include (but 72 201020252 is not limited to) the following target crops: Gu-J., (], wheat, barley, Li table, jade (including ordinary corn, popcorn and sweet) Wheat hot wheat, close crops); sugar beet (sugar beet and feed sweet:; rice, sorghum and lentils, beans, soybeans).: 4 dishes): legumes (broad bean, big Dan), oil plants (Rapeseed, father poor cucumber plants (West (four), cucumber, melon vitamin:, to 'Cai); , marijuana, jute); vegetables (snacks, $ (cotton ^, radish, ... onion, pepper, di-, di-sweet) "Guangcai ❹ ❹ = crops (fragrance, fruit trees, rubber trees, saplings); ornamental plants (,:, shrubs, broad-leaved trees and evergreen trees (such as conifers); and other plants 1 such as vines, shrub sub-categories of bushberry (such as blueberries), cane T-fruit "aneberry", cranberries ( (10) bark), peppermint, rhubarb, spearmint, sugar cane and turfgrass, including but not limited to cold-season turfgrass (eg bluegrass (bluegrass; corpse), such as precocious puberty Wo (Kentucky Xian (4); household (10) as L), common bluegrass (Pm Wv/a/b L.), Canadian bluegrass (cowpreisa L·) and annual bluegrass (annual bluegrass; (10) l.); Bentgrass (L.)' such as 匍匍 匍匍 ( ( (creeping bentgrass; dg7w&quot; 5· Huds.), thin shears (colonial bentgrass;

Sibth.), velvet bentgrass; /groins (10) L. and small sedge (redtop, dgr6»«s7/*s· L.); fescue (fescue; Festuca L.) » Tall fescue (Festuca arundinacea Schreb.) ' Meadow beetle (meadow fescue; Festuca Wim'OA* L_), and fine fescue, such as lycopene (creeping red 73 201020252 fescue ; Fesiwca L. ), Qiu's fescue (chewings fescue;

Festuca rubra var. commutata Gaud.)' sheepskin (sheep fescue; L.) and hard fescue (hard fescue; FeWwca /o«g//o//a); and ryegrass (ryegrass; lo/km L .), such as perennial ryegrass (Ζσ/z.ww L.) and annual ryegrass (Italian ryegrass; Italian ryegrass; Lo/km mw/iz_/7orwm Lam.), and Warm-type turfgrass (for example, Bermudagrass; C&gt;«oc?o«LCRich), including hybrid and common Bermuda grasses; Zoysiagrass; Ζορίβ//, St. Augustine Grass (St. Angustinegrass; (Walt.) Kuntze); and False Grass (centipedegrass; £rew〇c/^fl (Munro.) Hack·)). In addition, it should be understood that "crops" include those crops that have been rendered tolerant to pests and pesticides (including herbicides or multi-class herbicides) due to conventional methods of breeding or genetic engineering. Tolerance to, for example, herbicides means a lower sensitivity than the damage caused by the conventional crop variety '胄 by the herbicide. Crops can be modified or bred to be resistant to, for example, HppD inhibitors (such as mesotrione) to ppcpc ±, J inhibitors (such as glyphosate). Furthermore, the compounds of the formula I have the general use as fungicides and can therefore also be used in the related art for the application of the fungi, for example, for the use of pathogenic fungi, for example for protection. Technical materials (including wood and too small husk &&; 木材, wood related technology production °σ) for food storage or for sanitary management. Thus, the present invention proceeds further into the use of a compound of formula I for controlling fungi. 74 201020252 ^ A fungicidally effective amount of a compound of the invention is typically applied to a plant and/or plant propagation material. The amount used will of course depend on a number of factors, such as plant or propagation material, fungal type, and particular compounds of the invention. When the compound of formula I is used in the method of the invention, it may be formulated in unmodified form or preferably together with carriers and adjuvants conventionally employed in the formulation art. The present invention is therefore also directed to a composition for controlling fungal infections comprising a hydrazine compound as defined above and an agriculturally acceptable carrier or diluent. The agrochemical composition typically contains from about 9% by weight to about 99% by weight, preferably from 5% to 5% by weight of the compound of formula I; 929 weight. /. Up to 1% by weight, preferably 99.8% by weight to 5% by weight, of the solid or liquid adjuvant; and 〇% by weight to 25% by weight, preferably 〇% by weight to 25% by weight of the surfactant. The agrochemical compositions and formulations of the present invention are suitable for use in the development of disease yokes. The ratios and frequencies of use of the formulations are those known and used in the art and should be based on the risk of fungal pathogen infestation, the stage of development of the plant, as well as the location, timing and method of application. The advantageous application rate is usually 5 g to 2 kg of active ingredient per a hectare (ha) (a.i.), preferably 1 〇 - Ο 1 kg a. 1./ha, optimally 20 g to 600 g a.i./ha. When used as a seed soaking agent, a suitable application rate is 1 〇 mg to 1 g of active substance per kg of seed. In fact, as indicated above, the agrochemical composition comprising a compound of the formula (usually in the form of a formulation containing various adjuvants and carriers known or used in the industry is generally employed. Therefore, it can be formulated into granules, Wettable or soluble powders, emulsifiable concentrates, pastes, powders, flowables, solutions, suspensions or emulsions, or controlled release forms (such as 75 201020252 microcapsules). The invention is described in more detail below and may contain as little as about 0.5% by weight up to as much as about 95% or more by weight of active ingredient. The optimum amount depends on the formulation, the application equipment and the nature of the phytopathogenic fungus to be controlled. And set.

The suspension concentrate is an aqueous formulation in which finely divided solid particles of the active compound are suspended. Such formulations include anti-settling agents and dispersing agents and may further comprise a moisturizing agent which enhances activity as well as antifoaming agents and crystal growth inhibitors. These concentrates are diluted in water at the time of use and are usually applied as a spray to the area to be treated. The amount of active ingredient may range from about 5% to about 95% of the concentrate. Wettable powders are in the form of finely divided particles which are readily dispersed in water or other liquid carrier. The particles contain the active ingredient retained in the solid matrix. Typical solid substrates include Fuller's earth, kaolin clay, vermiculite, and other wettable organic or inorganic solids. Wettable powders generally contain from about 5% to about 95% of the active ingredient together with minor amounts of wetting, dispersing and emulsifying agents. An emulsifiable concentrate is a homogeneous steroid which is dispersible in water or other liquids and which may be formed from the active compound and a liquid or solid emulsifier or may also contain a liquid carrier such as xylene. Heavy aromatic naphtha (hea aromat丨c naphtha), isophor copper and other non-volatile organic solvents. These concentrates are dispersed in water or other liquids in % and are usually applied in spray form to the area to be treated. The lingual component may be in the range of from 0.5% to about 95% of the concentrate. The granule formulation includes the drag team &lt; - the extrudate and the relatively rough and usually applied in the undiluted π &amp; λ setting to control the phytopathogenic phase 76 201020252 〇❹ The area of the bacteria. Typical carriers for particle formulations include sand, fuller's earth, attapulgite clay, bentonite, montmorillonite clay, vermiculite, perlite, calcium carbonate. , brick, pumice, pyrophyllite, kaolin, dolomite, anhydrite, wood flour, crushed corn cob, ground peanut shell, sugar, sodium chloride, sodium sulfate, sodium citrate, boric acid Sodium, magnesia, mica, iron oxide, oxidized, titanium oxide, cerium oxide, cryolite, gypsum, diatomaceous earth, calcium sulphate and other absorbing active compounds or organic or inorganic substances which may be coated with active compounds . Granule formulations typically contain from about 5% to about 25% active ingredient, which may include surfactants (such as heavy aromatic naphtha, kerosene and other petroleum or vegetable oils) and/or adhesives (such as dextrin, Glue or synthetic resin). Powders are active mixtures of active ingredients with finely divided solids such as talc, clay, shell powder and other organic and inorganic solids used as dispersants and carriers. The capsule (4) encapsulates the active ingredient in a inert material. =2. The outer casing allows the encapsulated substance to be controlled at a rate (4). Typical ===:= about 9 wide. Micron. A solvent may also be included in addition to the object. Encapsulated particles: The granules, when 笪 π π 一 1 哥 Μ Μ Μ Μ 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔 多孔The diameter of the particles is typically at 1 millimeter, and the dot is preferably 1 to 2 millimeters. The granules are formed by extrusion or naturally occurring. Examples of such materials are insects to 77 201020252 stone, sintered clay, kaolin, magnesium aluminum sepiolite clay, sawdust and carbon particles. Shell or membrane materials include natural and synthetic rubber, cellulosic materials, stupid ethylene butadiene copolymers 'polyacrylonitrile, polyacrylates, polyesters, polyamines, polyureas, polyurethanes and yellows. Raw acid starch. Other formulations suitable for use in agrochemical applications include simple solutions of the active ingredient in a solvent wherein the active ingredient is completely soluble at the desired concentration, such as acetone, burnt naphthalene, diphenylbenzene, and other organic solvents. It is also possible to use a pressurized sprayer' in which the active ingredient is dispersed in the form of a fine powder due to vaporization of the low-boiling dispersant solvent carrier. Suitable agricultural adjuvants and carriers suitable for formulating the compositions of the present invention to the types of formulations described above are well known to those skilled in the art. Suitable examples for different categories are found in the non-limiting list below. Liquid carriers which can be used include water, toluene, diphenylbenzene, naphtha, sputum 'yield, acetone, mercaptoethyl ketone, cyclohexanone' acetate needle, acetonitrile, acetophenone, amyl acetate, 2 - butanone, chlorobenzene, cyclohexane, cyclohexanol, alkyl acetate® 曰'dipropane S and alcohol, 1,2-dipropane, diethylamine, p-diethylbenzene, di-ethyl s, Diethylene glycol rosinate, diethylene glycol butyl ether, diethylene glycol ethylene glycol goxide, N,N-dimethylformamide, dimethyl hydrazine, 1,4-diene.恶^, - propyl alcohol, dipropylene glycol keaki, dipropylene glycol dipropylene glycol vinegar, dipex red f d. generation 〖diproxU〇i) 'alkyl pyrrolidone, ethyl acetate, 2-ethyl alcohol Ethyl carbonate, 1,1,1-trichloroethane, 2-heptanone, α-epene, d-limonene, benzene furnace rt oleyl alcohol, ethylene glycol butyl ether, ethylene glycol methyl ether , γ_丁内g曰, 甘〉由,-7 酉 glyceride, monoacetin, triacetin, hexadecanol, isoamyl acetate, isobornyl acetate, isooctane, isophora 78 201020252 ❺

Ketone, cumene 1 bean woven isopropyl vinegar, lactic acid, laurylamine, mesityloxyl (mesityloxlde), methoxypropanol, methyl isoamyl ketone, decyl isobutyl ketone, laurel Acid A, octanoic acid, oleic acid methyl ester, di-halogen methane, m-methyl |, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene 1, poly Ethylene glycol (PEG400), propionic acid, propanol, propanol monomethyl, p-dimethyl #, toluene, triacetic acid, triethylene glycol, xylene continuous acid, stone it, mineral oil, three Gas bake, whole gas ethylene' acetic acid B, acetic acid, butyl acetate, methanol, ethanol, isopropanol and hydrazine are sub-alcohols (such as pentanol, tetrahydrofurfuryl alcohol, hexanol, octanol, etc.) ), ethylene glycol, propylene glycol, glycerol, N, methyl pyrrolidone and the like. Water is generally the carrier selected for diluting the concentrate. Suitable solid carriers include talc, titanium dioxide, pyrophyllite clay, vermiculite, magnesium aluminum sepiolite clay, kieselguhr, white earthworm, diatomaxaeous earth, lime, calcium carbonate, bentonite, bleaching Soil, cotton shell, wheat flour, soy flour, pumice, wood flour, walnut shell powder, lignin and the like. A wide range of surfactants are suitable for use in one of these liquid and solid compositions, especially those compositions which are designed to be diluted with a carrier prior to administration. When used, such agents typically constitute from 5% by weight to 15% by weight of the formulation # can be anionic, cationic, nonionic or polymeric in character and can be used as a ceramifying agent, wetting agent, suspending agent or Other purposes.典=Surfactant includes salt of county sulfuric acid sl, such as lauryl sulfate II = : 铋 'alkyl sulfonate 'such as calcium dodecyl benzene sulfonate; alkyl phenol - decane addition product, Such as nonylphenol_C18 ethoxylate; alcohol·epoxy hospital 79 201020252 addition product 'such as tridecyl alcohol-c16 ethoxylate; soap, such as sodium stearate; Sodium dibutylnaphthalene sulfonate; sodium dialkyl sulfonium sulfosuccinate such as sodium bis(2-ethylhexyl) sulfosuccinate; sorbitol ester, such as sorbitan oleate; quaternary amine , such as gasified lauryl trimethylammonium; polyglycol ester of montmorillonic acid, such as polyethylene glycol stearate; block copolymer of ethylene oxide and propylene propylene; and Alkyl esters and dialkyl phosphate salts. Other adjuvants commonly used in agricultural compositions include crystallization inhibitors 'viscosity regulators, suspending agents, spray droplet regulators, pigments, antioxidants, hair foaming agents, defoamers' photoblocking agents, compatibilizers, consumer Foaming agents, chelating agents, neutralizing agents and buffers 'corrosion inhibitors, dyes, odorants, spreaders, penetration aids, nutrients, softeners, lubricants' adhesives and the like. The biocidal active ingredient or composition can be further used in the present monthly method and can be administered simultaneously or sequentially with the compound of formula (1). When applied simultaneously, such other active ingredients may be formulated or comminuted with the compounds of the invention: for example, in a spray can. These other biocidal active ingredients may be fungicidal d herbicides, insecticides, bactericides, snails, nematicides and/or plant growth regulators. Examples of insecticidal compounds include, for example, perrnethrin, which are used in the compositions/methods of the invention (but are not limited to) pyrethroids (cypermethrin, Fenhua, and f J differentiation judgment (fenvalerate), yifenli (esfenvalerate), girlfriends (A, brother 'take τ (deltamethrin), cyha丨othrin (cyha丨othrin) (specifically, into _ 赛洛胥 &amp; contest) , bifenthrin, 80 201020252 fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (eg ethofenprox), Naturai pyrethrin, tetramethrinhs-s-bi〇aUethrin, fenfluthrin, prauethrin and 5-benzoquinone- 3-furyl mercapto-(丘)-(111,3 3)-2,2-dimethyl-3-(2-o-oxysulfur[)-east-3-phenylidenemethyl)cyclopropanoic acid Ester); organophosphates (such as profenofos, sulprofos, acephate, methyl benzobalazone) Parathion ), azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, Monocrotophos, tribronium, triazophos, methamidophos, dimethoate, phosphamidon, maiathion, chlorpyrifos , phosalone, terbufos, fensulfothion, fonofos, pho rate, phoxim, methyl mouth (pirimiphos-methyl) &gt; pirimiphos-ethyl, fenitrothion, fosthiazate, and diazinon; urethanes (including amine hydrazines) Acid aryl esters, such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, diazepam Aldicarb, thiofurox, butyl plus Baofu Carbosulfan), benzene.恶威81 201020252 (bend i ocarb), zhongweiwei (fen〇bucarb), chlorpyrifos (pr〇p0xur), methomyl and chlorpyrifos (〇xamyl); awkward urea (such as two Diflubenzuron, triflumuron, hexaflumuron, fiufenoxuron, and chlorfluazuroii; organotin compounds (such as cyhexatin phenylbutyltin) (fenbutatin oxide) and oxacyclotin (azocyclotin). More than saliva (such as tebufenpyrad and fenpyroximate); macrolides (such as avermectin or milbemycin, such as abamectin) ), emamectin benzoate, ivermectin, milbemycin, spinosad, and azadirachtin; hormones or pheromones ( Pheno mone ), organic gas compounds (such as endosulfan ' six gasified benzene, DDT, qidan (chl〇rdane) and diltrin (dieldrin)); moon rice (such as chlordimeform ) and amitraz (amitraz); fumigants (such as chloropicrin, diclofen, methyl desert, and metam); gasification of nicotine compounds (such as Yida) Amine (imidacloprid), thiacloprid, acetamiprid, nitenpyram, and thiamethoxam; diterpenoids (such as tebufenozide, ringworm) Chromium (chromafenozide) and methoxyfenozide); diphenyl ether (Such as Dai Fenlan (diofenolan) -propan ° and ether (pyriproxifen)); Indoxacarb (indoxacarb); insect cochlear carbonitrile (the chlorfenapyr); and Choi ketone 1-0 (pymetrozine) ° 201020252

Examples of herbicidal compounds for use in the compositions/methods of the invention include, but are not limited to, 2,3,6-TBA, 2,4-D, 2,4-DB, acetochlor, and azurene Acifluorfen-sodium, aclonifen, acrolein, alachlor, alloxydim, ametryn, amicarbazone, Amidosulfuron, aminopyralid, aminotriazole, amitrol, aminole, anilofos, asulam , atrazine, avivycine, azafenidin, azimsulfuron, BAY FOE 5043, beflubutamid, benzallin ), bencarbazone, benfluralin, benfuresate, bensulfuron-methyl, b.ensulide, bentazone, Benzfendizone, benzobicyclon, benzofenap, double propionate Bialaphos, bifenox, bispyribac-sodium, borax, bromacil, bromobutide, bromophenoxim, bromoxynil (bromoxynil), butachlor, butafenacil, butamifos, butralin, butroxydim, butabutene, benzene Cafenstrole, carbeamide, carfentrazone-ethyl, chloransulam methyl, chlorbromuron plasty S. 83 201020252 (chlorflurenol- Methyl), chl〇ridazon, chlorimuron-ethyl, gas acetic acid, chl〇rotoluron, chlorpropham, chlorsulfuron, Chlorthal-dimethyl, cinidon-ethyl, cinmethylin, cinosulfuron, clef0Xydim, sowing method Profoxidim ), clethodid ), clodinafop-propargyl 'clomazone, clomeprop, ci〇pyralid, cloransulam, acesulfame Methyl ester (cioransuiam-methyl), cumuluron, cumyluron, cyanamide, cyanazine, CyClaniiide, cycloate , cyclosulfamuron, cycloxydim, Cyhalofop, cyhalofop-butyl, cyprosuifamide, daimuron , dalapon, dazomet, desmedipham, desmetryn, dicamba, dichlobenil, dichlorprop, 2,4-dip propionate Dichlorprop-P, diclofop-methyl, diclosulam, difenzoquat metilsulfate 'diflufenican ), diflufenzopyr, dimefuron, and piperidan (dimepi) Perate ), dimethachlor, dimethametryn, dimethenamid, dimethenamid 201020252 (dimethenamid-P), dimethipin, dimethalin, enemies Dinitramine, dinoterb, diphenamid, dipropetryn, diqUat, ibromide, dithiopyr, diquat Diuron, DNOC, DSMA, end〇thal, EPTC, esprocarb, ethalfluralin, ethametsulfinron-methyl, ethephon Ethephon), ethofumesate, eth〇Xyfen_ethyi, ethoxysulfuron, etobenzanid, fenclorim, fine Fenoxapr〇p_p_ethy丨, fentrazamide, ferrous sulfate, fiamprop, flamprop-M, flazasuifuron, difluorosulfonate Amine (florasulam), voltapodyl ester (f]uaz Ifop_butyi), fluazifop-P-butyl, fluaz〇iate, flucarbazone sodium, fluoride. Flucetosulfuron, fiuchl〇ralin, flufenacet, fiufenpyr_thyi, flumetralin, flumetsulam , flumiclorac-pentyl, fiumi〇xazin, flumipropin, fluometuron, fluoroglycofen-ethyl , fiuoxaprop, flupoxam, fiupropacil, flupropanate &gt; flupyrsulfuron-methyl-sodium , flurenol , flufenate 85 201020252 fluridone , flurochloridone , fluroxypyr , flurtamone , 0 valerate

(fluthiacet-methyl), fluxofenim, fomesafen, foramsulfuron 'fosamine, glufosinate-ammonium, glyphosate (glyphosate), halosulfuron-methyl, haloxyfop, haloxyfop-P, HC-252, hexazinone, methyl oxalic acid (imazamethabenz-methyl ) 'Imazamox, imazapic, imazapyr, imazaquin, imazethapyr ' 〇 Compared with "imazosulfuron", indanofan, iodosulfuron, iodosulfuron-methyl-sodium, ioxynil, isopropyl Isopropazol, isoproturon, isouron, isoxaben, isoxachl〇rtole, isoxadifen, isoxazole Isoxafiuto丨e, isoxapyrifop, karbutylat e), KIH-485 'lactofen, lenacil, linuron, MCPA, MCPA-thioethyl 'MCPB, 2-methyl-4-propionic acid (mecopΓop), high 2-methyl-4-propionic acid (mecoprop-P), mefenacet, mefenpyr diethyl' mefluidide, sulfonamide Mesosulfuron methyl, mesotrione, mesotrione, 恶 》 met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met met

Metazachlor, rnethabenzthiazuron, methazole, methyl isothiocyanate, methyl decanoic acid, methyldymron, metobenzuron ), metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron-methyl , MK-616, molatar, monolinuron, MSMA, naproanilide, napropamide, naptalam, NDA-402989, gravy (neburon), nefenacet, nicotine, nicosulfuron. Nipyrallofen, n-methyl-glyphosate, citric acid, norflurazon, oleic acid (fatty acid), orbencarb, orthosulfamuron, yellow Oryzalin, oxaciclomefone, oxadiargyl, oxadiazon, epoxy. Oxalsulfuron, °oxaziclomefone, oxyfluorfen, pebulate, pendimethalin, penoxsulam , pentachlorobenzene g, vegetable grass, pentanochlor, ring 戍. Pentoxazone, pethoxamid, petroleum, phenmedipham, (R) phenoxaprop-P-ethyl(R), amine picolinic acid (pici) 〇rarn), picolinafen, pinoxaden, piperophos, pretilachlor, primisulfuron, flufensulfuron Primisulfuron-methyl, 87 201020252 Procarbazone, prodiamine 'gas. Profluazol, profoxydim, prohexcadion calcium, prometon, prometryn, propachlor, propanil, Propaquizafop, propazine, propham, propisochlor, propoxycarbazone propoxycarbazone-sodium, pentylene grass Proyzamide, prosulfocarb, prosulfuron, pyraclonil, pyragram, pyraflufen-ethyl ' ° The performance of the pyro (Pyrasulfotole), the pirate of the pyrazolynate, the pyrazosulfuron-ethyl, the pyraz〇x (yfen), the bite (pyribenzoxim) Pyributicarb, pyridafol, pyridate, pyrifalid 'pyriminobac-methyl, β pyrimansulfan Cyclomethasone naphtha

(pyrithiobac-sodium), quinclorac, quinmerac, quinoclamine, quizalofop, quizalofop-P Rimsulfuron, sequestren, sethoxydim, siduron, simazine, simetryn, S-isoprostamine S-metolachlor, sodium sulphate, sulcotrione, sulfentrazone, sulfometuron-methyl, sulfosate, sulphur rejuvenation 88 201020252

Sulf (sulfosulfuron), sulfuric acid, tar, TC A sodium salt, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, special Terbacil, terbumeton, terbuthylazine, terbutryn, thenylchlor, thiazafluron, thiazimin ), 0 thiazopyr, thiencarbazone, thifensulfuron-methyl/thiameturon-methyl, thiobencarb, tiocarbazil, Topemei Topramezone, tralkoxy dim, trial late, triasulfuron, triaziflam, tribenuron-methyl, green Triclopyr, trietazine, triflosulam, trifloxysulfuron trifloxysulfuron-sodium, trifluralin, fluoride Sulfonamide Ester (triflusulfuron-methyl), trinexapac-ethyl (trinexapac-ethy]) and the determined long-trifluoromethyl Yue (tritosulfuron). Examples of fungicidal compounds for use in the compositions/methods of the invention include, but are not limited to, acidified benzopyrene, CGA245704, ancymidol, alanycarb, Adi Aldimorph, 0 sylvestre (amisulbrom), anilazine, azaconazole, azoxystrobin, benaxyl, benzodia (benthiavalicarb), benomyll (benomyl), biloxazol, bitertanol, 89 201020252 bixafen, blasticidin S, bokley Boscalid ), sputum. Sitting (bromuconazole), bupirimate, captafol, captan, carbendazim, chlorhydrate chlorhydrate, carboxin ) 'Carpropamid, carvone, CGA41396 'CGA41397, chinomethionate, chloroneb, chlorothalonil, chlorozolinate,克克坐康 (clozylacon) 'Copper-containing compounds (such as copper oxide, copper oxyquinolate, copper sulfate 'COpper tallate and Bordeaux mixture), cyflufenamid ), Cymazine xanil, Cyproconazole, Cypr〇dinil, debacarb, Di-2-pyridyl disulfide ι, ι, _ Oxide, dichlofluanid, diclomezine, dichlozoline, dichlone, dicloran, diclocymet, carbaryl Diethofencarb) Difenoconazole, difenzoquat, diflumetorim, 0,0-di-isopropyl-s-phenylmercaptothiophosphate, dimefluazole, dimetconazole ), dimethomorph, dimethirimol, dimoxystrobin, diniconazole, dinocap, dithianon, gasified dodecyl Mercaptoammonium, dodemorph, dodine, doguadine, 201020252

Edifenphos, enestrobin, epoxiconazole, ethaboxam, ethirimol, etridiazole, σ oxa 0 Saccharomyces _ (famoxadone), imipenone _ (fenamidone ' RPA40721 3 ), fenarimol (fenarimol), fenbuconazole, fenfuram, fenhexamid (KBR2738) , fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, Fumi Iron (ferbam), ferimzone, fluazinam, fluopicolide, fludioxonil, fluoxastrobin, flumetover ), S YP-LI90 (flumorph), fluorine ° fluopyram, fluoroimide, fluoride saliva. Fluquinconazole, flusilazole, flusulfamide, fluolanil, flurifaol, folpet, fosyl-aluminium, Fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, IKF -9 1 6 (Cyazofamid), imazalil, imibenconazole, iminoctadine, dioctylamine triacetate, ipconazole, propyl Iprobenfos, iprodione, iprovalicarb (SZX0722), isopropyl butyl carbamate, isoprothiolane, sedative 91 201020252

(kasugamycin), kresoxim-methyl, LY186054, LY2 11795, LY248908,! Maneb, mancopper, mancozeb, mandipropamid, manganese, mefenoxam, mepanipyrim, dan Mepronil, metalaxyl, and leaf fungus. Meconazole, methasulfocarb, metiram, metiram-zinc, metominostrobin, metrafenone, myclobutanil , myclozoline, neoasozin, dimethyldithiocarbamic acid, nitrothal-isopropyl, nuarimol, α-family (ofurace), organic mercury compounds, oresastrobin, oxadixyl, oxasulfuron, oxine-copper, oxolinic acid , oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, 0 ratio. Penthiopyrad 'phenazin oxide, phosdiphen, acid, phthalide, picoxystrobin (ZA1963), polyoxin D ), polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, sputum in propineb, Propionic acid, proquinazid, prothioconazole, pyraclostrobin, pyrazophos, pyribencarb, pyrifenox, 92 201020252 Pyrimamine (pyrimethanil), pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compound, quinomethionate, vinofen (qUin〇xyfen) ), quintozene, silthiofam, simeconazole, sipconazole (F-155), sodium pentachlorophenate, spiroxamine (Spir) 〇xami Ne), sulphur, sulphur, schwefel, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole Thiabendazole ), thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram, tiadinil, amizoline (timibenconazole), tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, Tricyclazole, tridemorph, trifloxystrobin (CGA279202), triforine, triflumizole, triticonazole, vitamin A (validamycin A), vapani, vanphenal, vinclozolin, Zineb, ziram, zoxamide, 3- [5-(4·Phenylphenyl)-2,3-dimercaptoisoxazole-3-yl] ° ° °, 5-chloro-7-(4-methylbendidine_ 1 _yl)_6_(2,4,6-trifluorophenyl)[1,2,4]triazolo[l,5 -a]pyrimidine and oxime-(4-a-2-phenylphenyl)-indole-ethyl-4-methyl-benzenesulfonamide. Such formulations of the present invention for use in the methods of the present invention can be applied to areas in need of control by conventional methods 93 201020252, such as spraying, atomizing, pulverizing, spreading, coating or pouring. For example, powders and liquid compositions can be applied by using electric dusters, brooms and hand sprayers, and spray dusters. Formulations may also be administered from the aircraft in powder or spray form or by core application (r〇pe wick aPP丨iCatl〇n). Both solid and liquid formulations can also be applied to the soil in which the plant to be treated is located so that the active ingredient penetrates the plant through the roots. The invention can also be used for application on plant propagation materials to provide true g infection against plant reproduction (4) and for phytopathogenic fungi (4) in the soil. Suitably, the active ingredient can be applied to the plant propagation material to be protected by impregnating the plant with a liquid of the fungicide (4), in particular as a seed, or by coating the plant propagation material with a solid formulation. In special cases, other types of application may also have special features such as 'plant inserts or stems for serving reproduction. In addition, compounds of formula (1) as defined above may be used to treat humans and individuals: Fungal infection. The active compounds as described herein may be combined with a pharmaceutically acceptable carrier and may be administered or administered to such individuals or infections according to known techniques in an amount effective to treat the infection. Accordingly, it is accordingly also provided for the use of a compound of formula (I), as defined above, for the treatment of fungal infections in humans or animals, which is detrimental to f T, A w . The invention also provides for the treatment of a true (four) compound in a human or animal. V 1 } The invention will now be described by the following non-limiting examples. Those skilled in the art will quickly become aware of the appropriate changes to the procedures for reactants and reaction conditions and techniques. EXAMPLES Example 1 - Preparation of 5-(2-fluoroethyl)-7-(4-fluoro-phenyl)-6-indole _4_yl-5H-pyrrolo[3,2-d]pyrimidine

Step 1: 50.6 g of sodium metal (2,1 mol) was dissolved in 1.5 L of absolute ethanol under reflux. When the temperature is cooled to 3 〇. A mixture of 2,5 g of isonicotinic acid methyl ester (丨·5 mol) and 202 g of 4-fluorophenyl group in 0.5 L of anhydrous ethanol was added. The reaction mixture was refluxed for 4 hours, then cooled and poured into 1 .2 L ice water. 2 N HC1 was added until pH = 3 was reached and the yellow precipitate was filtered and dried (271 g). This material was suspended in a 48 〇 / 〇 HBr ' mixture and heated under i 〇〇 for 8 hours. After cooling, the reaction mixture was poured into ice water (1.2 L) and the pH was adjusted to 7 with a 25% ammonium hydroxide solution. After extraction with ethyl acetate, the organic layer was dried (MgSO4) (4_Fluorophenyl)_丨_(pyridine-4-yl)ethanone. Step 2: In the presence of a catalytic amount of acetic acid, hydrazine monohydrate (2 95 g), 2-(4-fluorophenyl)_丨_(pyridine-4-yl)ethanone (5 g, 23 mmol) Mix 95 201020252 dissolved in 500 mL of ethanol. The reaction was heated to reflux for 2 hours. The reaction mixture was then concentrated to 2 5 of the original volume and extracted in a solution of ethyl acetate / saturated gas. The organic phase was washed with water and water was taken over sulfuric acid. After concentration, the solid residue was recrystallized from ethyl acetate to give 3-6 g of [2_(4-fluoro-phenylpyridin-4-yl-ethylidene)- oxime as a brown crystal. Step 3: 2.73 g of [2-(4-fluoro-phenyl)_1-pyridine-4-yl-ethylidene]-indole was dissolved in 20 mL of toluene under argon. Then 2.95 g of 5-bromopyrimidine (18) Millol) and ι·8 g of sodium butyrate (ι8·5 mmol) were added to the mixture, followed by the addition of 1 g DPPF ([1-1,-bis-(diphenylphosphino))ferrocene ]) and 0.48 g PdClJDPPF) dioxane complex. The reaction mixture was heated at 1 ° C for 12 hours. The cooled reaction mixture was concentrated in vacuo and purified directly eluted eluted elute elut elut elut elut Phenyl)-1-pyridin-4-yl-ethylidene]-N,-pyrimidin-5-yl-indole. Step 4: 1.1 g of N-[2-(4-fluoro-indolyl)-1-pyridin-4-yl-ethylidene] in 4 mL of diethylene glycol in a metal bath under nitrogen. N,-pyrimidine-5-yl-indole was heated at 250 ° C for 4 hours. The cooled reaction mixture was then poured into a concentrated NaCl solution and extracted with ethyl acetate. The organic phase was washed with water and dehydrated with magnesium sulfate. After concentration, the solid residue was chromatographed to give 250 mg of 7-(4-fluoro-stupyl)_6_pyridine_4_yl_5 s. . set. Step 5: Add sodium hydride (52 mg, 1.29 mmol, 60% in oil) to 125 mg (〇·43 mmol) 7_(4-fluoro-phenyl)_6_ 201020252 at room temperature Mouth ratio. Ding-4-yl-5 Η-η ratio The L3,2-d]pyrimidine was combined in a bath of 6 mL of dimethyl decylamine. After 30 minutes at room temperature, 547 mg of 1-Han-2-fluoride was added to the reaction mixture φ. +10, ro, ^ After 90 minutes to the temperature, the reaction mixture was poured into a vaporized ammonium solution and extracted with ethyl acetate. The organic phase was washed with water and dried over magnesium sulfate. Λ Λ a a a 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化 纯化(4-Fluoro-phenyl)-6-pyridin-4-yl-5H-pyrrolo[3,2-d]pyrimidine. ❹ 实 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、

©Step 1: To a 2,3-dichloropyridine (1〇〇g, 0.671 mol) in dioxane (150 mL), add benzylamine (86·3 g, 〇_8〇5 m 〇1), triethylamine (140 mL, 1.0 m〇i)' and the reaction mixture was at 1 Torr. Heat underarm for 6_7 hours. After the reaction was completed, most of the solvent was evaporated under reduced pressure, and the reaction mixture was diluted with water and extracted with dichloromethane. The combined organic layer was washed with EtOAcqqqHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHHH 1 26 g (86%) 2-phenylhydrazino-3-pyrene was obtained. Step 2: Add Pd2(dba)3 (19·1 'g) to 97 201020252 2-gas-3-iodopyridine (100 g '0-418 mol) in anhydrous DMF (250 mL) under nitrogen atmosphere. , 0.021 mol, 5 mol%), triethylamine (300 mL) and Cul (0.398 g, 0.00 2 1 mol, 0.5 mol0 / 〇) ° The reaction mixture was cooled to hydrazine. . To the reaction mixture, trimethyldecyl acetylene (35.1 mL, 0.459 mol) was added dropwise. The reaction mixture was scrambled at room temperature (25 ° C) for 3-4 hours. After completion of the reaction, the reaction mixture was diluted with cold water and filtered through a pad of Celite. Subsequently, the mixture was extracted with ethyl acetate, and the combined organic layer was washed with brine and dried over sodium sulfate. The crude product was concentrated from the organic layer and purified by EtOAc (EtOAc/hexane, 4/96) to afford 71 g (81%) of s. Acetylene pyridine. Step 3. Under the nitrogen atmosphere, add 2-indole-based amino-3-pyrene (50 g, 0.228 mol) to dimercaptoamine (3〇〇mL), add 肆 (three Stupid phosphine) 巴巴 (0) ( 13.2 g ' 0.0114 mol ' 5 mol%). The mixture was heated to 70 C for 15 minutes to add cui (190.4 g, 0.217 mol) and triethylamine (500 mL) to this mixture. After stirring the mixture for 1 minute, a solution of 2- gas-3-dimethyl-stone acetylene pyridine in dimethylformamide was added dropwise, followed by the addition of tetrabutylammonium fluoride (119.2 g, 〇. 457 and ❹ tetramethylethylenediamine (20 mL). The reaction mixture was heated at u〇t for 5 hours. After completion of the reaction, the reaction mixture was filtered through celite, and the filtrate was diluted with cold water and dichloromethane The combined organic layers were dried over sodium sulfate, concentrated under reduced pressure and purified by EtOAc EtOAc EtOAc %) 2_(2_glycol ethynyl acridine)-3-phenylf-amino-aminopyridinium. Step 4: 2-(2-Chloro-4-ethynyl fluorenyl-3-ylbenzylamino). The solution of cultivating 98 201020252 (37 g, 0.115 m〇i) in dioxane (35 〇mL) was cooled to 〇 ° C. To the solution was added potassium tert-butoxide (389 g) under nitrogen atmosphere. The reaction mixture was stirred at room temperature (25 ° C) for 1 hour. After completion of the reaction, the reaction mixture was diluted with dichloromethane, washed with water and then extracted with a methylene sulfate. Make The combined organic layers were dried and concentrated under reduced pressure to give &lt;RTI ID=0.0&gt;&gt;&gt; Under nitrogen atmosphere, 'palladium acetate (丨23 g, 〇〇〇547 m〇b❹ 5 mol%), x-Phos (5.21 g, 0.011 mob; I 〇m〇i〇/0) and third A mixture of potassium alkoxide (18.4 g, 0.164 mol) in toluene/ethanol (2:1, 100 mL) was heated to 70 ° C. To this mixture was added dropwise 2-(2-pyridinyl)-1-benzene a solution of methyl-4,7·diindole (35 g, 0.1 1 m〇i) in toluene/ethanol (2:1 '150 mL). After the addition is complete, the reaction mixture is at 90 °C-100. After heating for 1-2 hours at ° C. After the reaction is completed, the solvent is evaporated under reduced pressure, and the reaction material is diluted with cold water, filtered through a layer of diatomaceous earth, and the aqueous filtrate is extracted with a gas of a gas. The layer was dehydrated and concentrated under reduced pressure to give 35 g (96%) of 2-(2-ethoxypyridinyl)-1 _ 曱 _ _ 4, 7 _ 丫 引 引 步骤 步骤 Step Step Step Step Next, 2-(2-ethoxyl group. π-based group) in methylene chloride (15 〇mL)_ι_benzyl_4 , 7-diπ丫D cited. (35 g, 〇·ιι mol) was cooled to 〇c, and the substance dissolved in dichloromethane (]〇〇mL) was added dropwise to the substance. 7 mL '0.11 m〇l). After the addition was completed, the reaction mixture was stirred at room temperature (25 ° C) for 1 hour. After the reaction is completed, the reaction mixture is quenched with aqueous sodium thiosulfate solution, extracted with di-methane, and hydrogen carbonate is used.

The combined organic layer was washed with a sodium aqueous solution. Concentrate under reduced pressure to give 40 g (92%) of 2-(2-ethoxyl. ratio: decidyl-di-di-bromo- 4,7-diindole, which is sufficiently pure to be used as it is. Next step: Step 7: Stir the palladium acetate (〇Λ ΛΛ._ ν 0:5 g, 0.0025 mol ' 5 mol%), X-Phos ( 2.33 g, 0.0049 mol, 1〇m〇1〇 under a nitrogen atmosphere. / ) and a mixture of acid-destroying (48 g, 0.147 mol) in toluene/ethanol π, 〇_ i, 60 mL) for 5-10 minutes. To this mixture, phenylboric acid (6.58 g '0.054 mol) and 2-(2-ethoxypyridinyl benzophenone _4,7-dioxin (20 g, 0.049 mol) in toluene were added dropwise /Ethanol (3:1,6 〇[[], after the addition is completed, 'The reaction mixture is heated at 5 ° C for 5 ^. After the reaction is completed, 'Evaporate the solvent under reduced pressure' to dilute the ruthenium material with water. And extracted with ethyl acetate. The combined organic layers were dehydrated by sodium sulphate and evaporated under reduced pressure to give 1 7 g (85 ° / 〇) 2-(2-ethoxyl&lt;» ratio π-based base 1 Benzyl-4,7-diindole' is sufficiently pure to be used as it is in the next step. Example 3: Ν-[4-(5-allyl-7_phenyl_5Η_pyrrole) And [2,3_b 卜比耕-6-yl)-α ratio biti-2-yl]-propanol preparation

Step 1: 2% (2 ethoxy-pyridyl)-3-phenyl-1-benzoinyl·4,7·diindole in 33% HBr (50 mL) in glacial acetic acid 17 201020252 mol) Heated for 6-7 hours under wot-ucrc. After the completion of the reaction, the excess hydrazine in the glacial acetic acid was evaporated, the reaction mixture was diluted with water, extracted with dichloromethane, and the organic layer was dried over sodium sulfate and concentrated under reduced pressure to give 13 g (82%) 2 - (2 - base group ratio _3_phenyl q _ benzoquinone _ 4,7 · 吖 丨 丨 丨 0, which is pure enough to be used as it is in the next step. Step 2: 2-(2-hydroxypyridyl)-3-phenyl_1-benzyl-3,7-diindole (13 g, 〇 in oxygenated phosphorus (5 〇 mL) 〇35 m〇1 ) was heated at 100 ° C - 110 ° C for 7 hours. After completion of the reaction, the oxygenated phosphorus was distilled off, and the reaction mass was neutralized with a 1 N sodium hydroxide water bath, and the aqueous phase was extracted with methylene chloride. The combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to give &lt;RTI ID=0.0&gt;&gt;&&&&&&&&&&&&&&&& The sputum bow I 哚 was used in the next step without further purification. Step 3 · 2-(2- gas ratio. base) in concentrated sulfuric acid (20 mL) - 3 - group - N-benzyl-4,7-diindole (11 g, hydrazine) 〇28 m〇1) Heat at 8〇〇c for 8 hours. After completion of the reaction, the reaction mixture was cooled to room temperature (25) and diluted with ice. The mixture was extracted with a two-gas toluene by adjusting the aqueous layer to a neutral and p p value. The combined organic layers were washed with aqueous sodium bicarbonate, dried over sodium sulfate &&lt;&quot;&&&&&&&&&&&&&&&&&&&&&&&&&&&&& -—. Hey. B was taken and used in the next step without further purification. Step 4: 'p-Methoxybenzoylamine (3.6g' 0.026 mol), palladium acetate (0.18 g, 0.00065 mol, 5 mol%), X-Ph〇s (0·62 g' under nitrogen atmosphere A mixture of 0.0013 mol, 10 mol%) and potassium butoxide (367 g, 0·〇33 mol) in toluene (25 mL) was heated to 7 ° C. To this mixture was added dropwise 2-(2-pyridinyl)-3-phenyl-4,7-diindole (4 g, 101 201020252 〇.〇13 in 曱l (25 mL) After the solution is added, the mixture is heated under 丨HTC for 7.8 hours. After the reaction is completed, the reaction mixture is filtered through the soil layer of Shixia, and most of the solvent is evaporated under reduced pressure, diluted with water, with two gases. Extraction by smoldering. The combined organic layers were dried over sodium sulfate, concentrated under reduced pressure, and purified by neutral oxidative chromatography (methanol / methane, m. 47%) 2_[2_(p-methoxybenzylaminomethyl)-acridinyl]-3-phenyl-4,7-dioxime. Step 5. To monomethylcarbamide (1〇) 2-[2-(p-oxooxy adenylamino)pyridinyl]-3-phenyl_4,7-diindole (2 g, 〇〇〇49 〇中' added carbonate planer 4g '0.012 mol), and the mixture was stirred at room temperature (25 C &gt; c) for 10 minutes. Allyl bromide (0.65 g, 0.0054 mol) was added dropwise to the mixture and stirred at room temperature (25 ° 〇 The reaction mixture was stirred for 15 minutes. After the reaction was completed, the reaction was diluted with water. The mixture was extracted with di-methane. The combined organic layers were washed with water, dried over sodium sulfate and concentrated under reduced pressure to give &lt;RTI ID=0.0&gt; Π-pyridyl]-3-styl-1 -fluorenyl-4-4,7-diindole, which was used in the next step without further purification. ❹ Step 6 · "Trifluoro" under a nitrogen atmosphere 2-[2-(p-methyl-based methylamino group) in acetic acid (5 mL). 11-by-bityl]-3-phenyl-N-blocky propyl-4,7-di-sigma fluorene (g '〇·〇〇4 mol) was heated at 50 ° C-6 (TC for 2 hours. After the reaction was completed), excess trifluoroacetic acid was distilled off under reduced pressure. The reaction mass was diluted with water and adjusted with 丨N sodium hydroxide. To the pH value of ', and extracted with dioxins. The combined organic layers were dehydrated with sodium sulfate and concentrated under reduced pressure to give 13 g (83%) of 2-(2-aminopyrene) Base)_3_Phenyl-1-l-propyl·4,7-di-β-inducing, 102 201020252 It is not used for further purification. Step 7: To pyridine (2 mL) 2-(2-Aminopyridinyl)_3_styl-1-isopropene暮_4 7 _ , Diterpene (〇.2 g, 0.000 Propylene gas (η , .b §, 0.00067 mol) was added dropwise to 6 mol) and the reaction was stirred at room temperature (25 ° C) for 15 minutes. After the reaction was completed, the pyridine was evaporated under reduced pressure with water. The reaction material was taken up and extracted with dioxane. The organic layer was washed with EtOAc (EtOAc) and water. The crude product was purified by flash chromatography on celite (ethyl acetate / hexanes, 3/20) to give 0,06 g (25%) of 2 - (2 - propylamino). The base is propyl _4,7_ dioxin. Example 4 -5-allyl-7-phenyl-6-pyridylpyrimidin &amp;pyrrolo[3,2-d]pyrimidine Step 1: sodium salt of 3-hydroxy-2-phenyl-acrylonitrile &quot; Acid B_(14.17g '0.19m〇1) is added dropwise to the cold liquid of methanol in decyl alcohol (prepared by dissolving i 〇.3 g sodium in i. )in. Next, the cyano cyanide (7) §, 0_17, 1) in the sterol is added dropwise to the above mixture. The reaction mixture was then heated to reflux until the white salt was completely precipitated. After cooling to room temperature, the reaction mixture was filtered through a Buchner funnel (EtOAc) and washed with diethyl ether and dried to give a white solid (2 1 g). Step 2: 2-[2-cyano-2 -Phenyl-ethylidene]-diethyl malonate The sodium salt of 3-hydroxy-2-phenyl-acrylonitrile, milk concentrate C 20 g, 〇·138 mol) is dissolved in water (700 A clear solution is formed in ml). Acetate (1 〇〇 ml) was added dropwise to the splicer and the mixture was stirred at room temperature for 1 Torr. The solution of the amine malonate di 103 201020252 ethyl ester (50 g, 0.22 mol) in methanol (300 ml) and triethylamine (20 mi) ^ was added dropwise to the previously obtained 3 - Hydroxy-2·phenyl-acrylonitrile in sodium salt solution' and the mixture was heated at 70 ° C for 8 hours. After cooling to room temperature, 'evaporation of sterol' was quenched with water and extracted with a gas. The combined organic extracts were washed with EtOAc (EtOAc m.). Step 3: Ethyl 3-amino-4-phenyl-1H-pyrrole-2-carboxylate at 0 ° C ' to 2-[2-cyano-2-phenyl-ethylideneamino]-propyl Diethyl ruthenium diacetate (28 g '0.093 mol) in a solution of methylation was slowly added with sodium methoxide (prepared by dissolving 5.4 g of sodium in 50 ml of sterol). The reaction mixture was then stirred at room temperature overnight. Methanol was evaporated, the residue was diluted in water and extracted twice with ethyl acetate. The combined organic extracts were dehydrated with Nad EtOAc (EtOAc)EtOAc. Step 4: 7-Phenyl-5H-pyrrolo[3,2-d]pyrimidin-4-ol 3 -Amino-4-benyl-1H-0 to 0 -2-carboxylic acid ethyl acetate (27 g , 〇·ΐ2 mol) 溶解 Dissolved in ethanol and stirred at room temperature for 10 minutes. Then, methyl acetate (27 g, 0.25 8 mol) was added to the above mixture and found at room temperature for 丄〇 minute. The reaction mixture was then heated to reflux for 8 hours. The reduced reaction mixture was washed with ethanol (25 ml×4) and dried to give 7-phenyl-5H-pyrrolo[3,2-d]pyrimidin-4-ol (21 g) as a white solid. Step 5: 4-Gas-7-phenyl-5H-pyrrolo[3,2-d]pyrimidine 104 201020252 Under an inert atmosphere, at 0. Under the armpit, add phosphorus oxychloride (1 2〇mi, 1〇v〇1) to the base 5H-n and [[3,2_d] _4_ol (12 g, 0.056 mol) in. The reaction mixture was then refluxed under hydrazine 5 for 4 hours. After cooling the reaction mixture to room temperature, the reaction was quenched by the slow addition of crushed ice and then extracted twice with ethyl acetate. The organic layer was washed with water and aq. NaHC.sub.3, dried over Na.sub.sub. Step 6: 7-Phenyl-5H-pyrrolo[3,2-d]pyrimidinium 4-S-7-phenyl-5H-pyrrolo[3,2-d]pyrimidine (5.1 g, 0.022 mol) Dissolved in methanol (5 〇mi) and added ammonium formate (8 4 g, 〇] 3 mol). The mixture was degassed and then carefully added under nitrogen to give 〇% pd/c (〇·47 g '1〇 m〇l%). The reaction mixture was stirred at room temperature overnight. The reaction mixture was then filtered through a pad of celite, followed by evaporation of decyl alcohol, and the residue was diluted with water and extracted with di-methane. The organic layer was washed with water, dried over Na 2 EtOAc EtOAc EtOAc EtOAc ® Step 7 : 6 -Bromo-7-phenyl_5H-° ratio slightly [3,2-d] mouth bite 7-phenyl-5H-&quot;bi-[3,2_d]pyrimidine (1〇 g, 〇〇47 m〇]) dissolved in decyl alcohol (60 ml) and cooled to (TC. followed by a cold solution of bromine (7 68 g '0.042 mol) in acetic acid (20 ml) under 〇. It was added dropwise to the reaction mixture. The reaction mixture was stirred at room temperature overnight. The reaction mixture was filtered over Buchner funnel. The obtained solid was washed with diethyl ether and dried under vacuum to give 6-bromo-7-phenyl- 5H-pyrrolo[3,2-d]pyrimidine (10.9 g) 0 105 201020252 Step 8: 7-Phenyl-6-acridin-4-yl-5H-pyrrolo[3,2-d]pyrimidine 6 -Bromo-7-phenyl-5H-pyrrolo[3,2-d]pyrimidine (1.0 g, 0.003 mol), 4-pyridylboronic acid (〇'53 g, 0.004 mol), (Ph3P)2PdCl2 (〇' A mixture of 25 g, 10 mol%) and sodium carbonate (0.77 g, 0.0073 mol) was dissolved in DME:H2〇:ethanol (i〇ml/7:3:2) and heated in a microwave at i10 °c 2 The reaction mixture was filtered through a pad of celite, and then the filtrate was quenched with water and extracted with di-methane. NaJC»4 was dehydrated and concentrated under vacuum. The residue was purified by column chromatography to give a s. d]Bite bite (0.558 ❽ g ) 0 Step 9: 5-Allyl-7-phenyl-6-°pyridin-4-yl-5H-pyrrolo[3,2-d] Pyrimidine 7-Benzene Base-6-.pyridyl-4-yl-5H-pyrrolo[3,2-d]pyrimidine (0.2 g, 0.0007 mol) was dissolved in tetrahydrofuran (10 ml), followed by dropwise addition of hydroxide dissolved in water Sodium (〇〇88 g, 〇〇〇22 m〇1), followed by the addition of allyl (0.132 g' 〇·〇〇&quot; m〇i). The reaction mixture was then allowed to stand at room temperature for 2 hours. Evaporation, the mixture was diluted with ethyl acetate: hydrazine was dried over Na 2 SO 4 and concentrated in vacuo. ·Ki·5H′Luo[3]pyrimidine (〇·1 g) 〇106 201020252

[3,2-c] 嗒耕4_amine·嗒耕_3_ol ❿ to 4,5-dichloro-3-yl 1 荅〇^(51&lt;() Λ - 〇_ Λ τW .69 g, 0.325 mol) in a solution of ethanol [1.8 L), add τ . λ / 1 ^ . 158 mL hydrated hydrazine (1 〇 equivalent, 3.25

Mol) The reaction mixture is then heated to reflux overnight (after which time it changes from white to a smudge suspension) and then to an orange suspension and finally to a color/liquid mixture. The reaction mixture was cooled to room temperature and 9 Torr Isolute was added. The solvent was removed in vacuo and the residue was purified eluting with EtOAc EtOAc EtOAc EtOAc EtOAc Et3N (90:9:1) is eluted. 44.1 grams of solid material obtained from the column was mixed with 22 mL of water and cooled to hydrazine. 〇 Overnight. The filter was washed with cold water and dried at 45 ° C under a reduced pressure of 14 mm (Hg.) overnight to obtain 16.32 g of orange crystals. lHNMR (400Mhz, CDCl3) 7.45ppm, lH, d, J = 4.64Hz · 6_30ppm, 2H, bs; 6.16ppm, 1H, d, J=4.75Hz ° 4-[2-phenyl-1-pyridine-4· 5-Ethylamino]-indole-3-ol 0.5 g of 4-(1,1-dimethoxy-2-phenyl-ethyl)-pyridine was dissolved in 107 201020252 « 1 mL DMF One drop of concentrated sulfuric acid was added and the mixture was heated to 90 °C. 1.09 grams of 4-amino- in 2.5 ml DMF was added over 2 minutes. The solution was -3 -ol' and the reaction mixture was further heated to 12 5 overnight. After cooling to room temperature, the mixture was washed with saturated aqueous NaHCO3 and extracted three times with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with EtOAc EtOAc 400 mg of the title compound are obtained in the form of an imine/enamine mixture. 1H NMR (400Mhz, D6-DMSO) 12.8ppm, 1H, bs; 〇12.5ppm, 1H, bs; 8.58ppm, 2H, dd, J=1.4 and 4.7Hz; 8.51ppm, 1H, s; 7.95ppm, 1H, s; 7.56ppm, 2H, d, J=7.3Hz; 7.49ppm, 2H, dd, J = 1.6 and 4.6Hz; 7.46ppm, 1H, d, J=4.7Hz; 7,41ppm, 1H5 d, J=4.7 Hz; 7.36ppm, 2H, t5 J-7.2Hz; 7.30ppm9 1H, t, J = 7.2Hz; 7.24ppm, 1H, bs; 6.3ppm, 1H, bs; 6.17ppm, 1H, d, J = 4.7Hz; 5.61 ppm, 1H, d, J = 4.8 Hz. (3 - gas - tower _ -4-yl) - [2 - stupid-1 - ° than cough-4-yl-ethylidene] • amine at 100 ° C '91 mg 4-[2-benzene The base-1-pyridin-4-yl-ethyleneamine-based hydrazin-3-ol and 11.4 mg of Me3NHCl were heated in 0.6 mL of P0C13 for 2 hours. After cooling to room temperature, the mixture was poured onto ice, mixed for a few minutes and neutralized with 4 Torr sodium hydroxide. It was then extracted with EtOAc, washed with EtOAc EtOAc EtOAc. The combined organic extracts were dehydrated by Na2SO4 and filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate / methanol 19/1 + 1% triethylamine. 53.5 mg of the title compound was obtained. 108 201020252 1H NMR (400Mhz, CDC13) 8.61ρρηι, 2H, bs; 8.44ppm, 1H, d, J=5.8Hz; 7.37-7.22ppm, 6H, m; 6.82ppm, 'ih, s; 6.53ppm, 1H, Bs; 6.13 ppm, 1H, d, J = 5.8 Hz. 7_Phenyl-6-° ratio biting-4-yl- 5H-d ratio n and [3,2-c] ° answer 387 mg (3-chloro-- morphine-4-yl)-[ 2-Phenyl-1-° ratio. D--4-yl-ethylidene]-amine, 444 mg DABCO and 88 mg (Ph3P)2PdCl2 were dissolved in DMF (5.8 mL) and stirred at 110 ° C for 3.5 hours. After cooling to room temperature, the mixture was washed with a saturated aqueous solution of NaHC 3 and extracted twice with ethyl acetate. The combined organic extracts were dried over NazSO4, filtered and concentrated in vacuo. 22 1 mg of solid material was obtained which contained a very small amount of product. The resulting aqueous phase was then filtered to dry at 40 ° C under a reduced pressure of 14 mm (Hg) overnight. Thus, 1 6 8.5 mg of the title compound was obtained. 1H NMR (400Mhz, D6-DMSO) 12.48ppm, 1H, bs; 9.01ppm, 1H, d, J = 5.8Hz; 8.65ppm, 2H, d, J = 5.8Hz; 7.71ppm,1H, d, J = 5.9 Hz; 7.57ppm, 2H, d, J = 7.2Hz; 7-51ppm, 2H, d, J=5.9Hz; 7.46ppm, 2H, t, J = 7.2Hz; 7.39ppm, ® 1H, t, J = 7.2 Hz ° 7-Phenyl-5-prop-2-ynyl-6-pyridine_4_yl_5H_pyrrolo[3,2&lt;] tillage 108 mg 7-phenyl-6-pyridine-4- The benzyl-5H-pyrrolo[3,2_c] was dissolved in DMF (1.2 mL) and added with a slight cooling of 9 NaH (60% '1.2 eq.). The mixture was stirred for 15 minutes, after which 4"L of propargyl bromide was added. After 3 hours at room temperature, a saturated aqueous solution of lysine (10) was added dropwise and the mixture was diluted with dioxane to extract the mixture. Dehydrated, filtered and evaporated to give a crude compound eluting with EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc /MeOH/Et3N 93:6:1 elution) The latter was purified twice to give 6 mg of the title compound. 1H NMR (400Mhz, CDC13) 9.16 ppm, 1H, d, J = 5.9 Hz; 8.77 ppm, 2H, dd , J = 1.3 and 4.6 Hz; 7.59 ppm, 1H, d, J = 5 9 Hz. 7.56 ppm, 2H, d, J = 7.7 Hz; 7.42 ppm, 2H, dd, J = 1.5 and 4 4 Hz. 7.33 ppm, 2H , t, J = 7.6 Hz; 7.28 ppm, 1H, t, J = 7.6 Hz; 4.77 ppm, 2H, d, J = 2.5 Hz; 2.47 ppm, 1H, t, J = 2.5 Hz. Derivatives·· 7-(4-fluoro-phenyl)-6-indolepyridin-4-yl-5H-pyrrolo[3,2-c]. morphine 1H NMR (400 Mhz, CD3OD) 8.98 ppm, 1H, d, J = 5.9 Hz; 8.60 ppm, 2H, dd, J = 1.5 and 4.8 Hz; 7.77 ppm, 1H, d, J = 5.9 Hz; 7.59-7.56 ppm, 4H, m; 7.2 ppm, 2H, t , J = 8.8 Hz. 5-allyl-7-(4-fluoro-phenyl)_6-.pyridin-4-yl-5H-.pyrho[3,2-c] 嗒耕1H NMR (400Mhz , CDC13) 9.11ppm, 1H, d, J = 5.9Hz;

8.73ppm, 2H, d, J = 5.5Hz; 7.55ppm, 2H, dd, J = 5.4 and 8'8Hz; O 7.42ppm, 1H, d, J = 5.9Hz; 7.33ppm, 2H, d, J=6Hz ; 〇 2ppm, 2H, t, J = 8.8Hz; 5.91ppm, 1H, tdd, J = 4 6 and 1〇5 and 17 1Hz; 5.27ppm, 1H, d, J=l〇.5Hz; 4.93ppm , 1H, d, J = i7.1 Hz; 4.66 ppm, 2H, m. Example 6: Biological Activity of Compounds of the Invention As described below, the compounds of the invention were tested in a leaf disc assay to determine their prophylactic effect against various fungal species. In all cases, 110 201020252 test compounds were dissolved in DMSO and diluted to 2 ppm in water. The final test solution contained 2% DMSO and 0.025% Tween® 20. Han) Erysiphe graminis fsp h〇rdei (barley powdery mildew) and barley net blotch (barley net blotch): placing barley leaf slices on In a 24-well plate, it was sprayed on a counter-mortem and sprayed with a solution of the test compound. After the sections were completely dried (24 hours), they were inoculated with a spore suspension of the fungus. After appropriate incubation, the activity of the compound was evaluated as a prophylactic fungicidal activity 4 days after inoculation (barley pathogen) or 7 days later (manganese powdery mildew). b) wheat powdery mildew (£〇^&gt; heart γ kb y ^ (wheat powdery mildew), wheat stalk rust (grain...) (brown rust) and A. oxysporum (Wheat blight (^) :^ume blotch): Wheat leaf slices were placed on agar in 24-well plates and sprayed with a test compound solution. The slices were completely dried (24 hours). After inoculation with the spore suspension of the fungus, after appropriate incubation, the compound was evaluated 4 days after inoculation (A. oxysporum), 7 days later (Wheat powdery mildew) or 8 days later (Wheat stalk) Activity as a prophylactic fungicidal activity. &lt;0 rice porcine (rice blast): rice leaf slices were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After the sections were completely dried (24 hours), they were inoculated with a spore suspension of the fungus. After appropriate incubation, the activity of the compound was evaluated as a prophylactic fungicidal activity 5 days after inoculation. d) Gray mold (grey mould) )): Put the stupid bean leaf disc on 111 201020252 e ) Potato late blight Bacteria (potato/tomato): Spray the tomato leaf on a disk and spray the Phytophthora platensis with a solution of the test compound (the grape downy mildew is inoculated with the fungus suspension of the fungus. Activity as a preventative fungicidal activity. f)

Place on agar in a 24-well plate and inoculate with the discs completely dry (24 hours). After appropriate incubation, the inoculation is a prophylactic fungicidal activity. After the hour), the solution of the test compound was sprayed 4 days after the inoculation. After the 'spore suspension with fungi, the activity of the compound was evaluated after 3 days/tomato late blight (late blight of water placed in a 24-well plate to make the wafers completely dry (24 (downy Mildew of grapeWne)): Place the grape leaf disc on the agar in the well plate and spray with the test compound solution. Allow the wafers to dry completely (between i 2 hours and 24 hours) Thereafter, it was inoculated with a spore suspension of the fungus. After appropriate incubation, the activity of the compound was evaluated as a prophylactic fungicidal activity 7 days after the inoculation.

In the leaf disc assay described above, the following compounds (numbers corresponding to Tables 1, 2 and 3 above) control at least 80% of the following true i infections at 200 ppm: Plasmopara viticola: Μ; 1.2 1.3; 1.4; 1.18; 1.19; 1.20; 1.21; 1.22; 1-23; 1.34; 1.37; 1.38; 1.39; 1.42; 1.43; 1.44; 1.45; 2- 6; 2.7; 2.8; 2.9; 2.12 Wheat powdery mildew: 1.3; 1.4; 1.18; 1.19; 1.20; 1.21; 1.22; 1.36; 1.37; 112 201020252 1.44; 1.39; 1.42; 1.43; Puccinia glabrata: 1&gt;45;2.5;2.12; 2.13 1.21; 1.22; ι·42 ; 1.43 ; 1.44 ; bacterin spores in nutrient culture 1.3, 1.4, 1.5; 1.18; 1.19; i2〇.131; 1.34; 1.36; 1.37; 1.38; ι·39 ; &quot;5 ; 2.3 ; 2.4 ; 2.7 ; 2.8; 2.12 additionally 'The ability of the compounds of the invention to inhibit growth in true fluids was also tested.

Ο Ο ( ( (whea Ueafbi〇 (10)), six gray mold), rice pear (rice fever), Rhizoctonia solani (root rot; and rot and damping foot Ff)), yellow rot of e (10) als): Mix the fungi of the low temperature storage fungus directly into the nutrient medium (PDB riding the potato money (4) nutrient solution. The ppm (DMS0) solution was placed in a microtiter plate (10) well format) and a nutrient medium containing fungal spores was added. At 24. The test plates were incubated and the growth inhibition was measured photometrically after 72 hours (S. cerevisiae, Botrytis cinerea, P. sylvestris) or 48 hours later (Rhizobacter serrata, Fusarium oxysporum). b) Ultimate Pythium (slumping disease): Fungal hyphae fragments prepared from fresh liquid cultures are mixed in potato dextrose broth. The 20 ppm (DMS0) solution of the test compound was then placed in a 96-well microtiter plate and a nutrient medium containing fungal spores was added. At 24. The test plates were incubated under the arm and the inhibition of growth was measured photometrically after 48 hours. In the liquid culture assay described above, the following compounds (numbers corresponding to Tables I and II above) control at least 80% of the following fungi at 200 ppm. 113 201020252 Infection: Wheat sphaeroides: 1.3; 1.6; 1.7; 1.8; 1.19; 1.20; 1.21; 1.22; 1.23; 1.29; 1.31; 1.36; 1.37; 1.38; 1.39; .142; 1.43; 1.44; 1-45; 2.8; 2.12; 3.2 Pythium ultimum: 1.3; 1.4; 1.8 ; 1.9 ; 1.20 ; 1.24 ; 1.4〇 ; 1.42 ; 1.43 ; !-44 ; 1.45 ; 2.1 ; 2.2 ; 2.5 ; 2.6 ; 2.10 ; 2.12 ; 3.2 ;

Example 7 - HPLC method used

Method A (Water Alliance 2795 LC) with the following HPLC gradient conditions: medium formic acid

Solvent A: 0.1% in water/acetonitrile (9:1) Solvent B: 〇. 1% decanoic acid in acetonitrile • (minutes) A ( % ) B ( % ) 0 90 10 2.5 0 100 2.8 0 100 2.9 90 10 Flow rate (ml/min) 1.7 1.7 ^ Column type '· Wa (10) atlantis dci8 ; Column length: 2 mm; Column inner diameter: 3 quasi-half. Pen rice, particle size '3 μm; Temperature: 4〇 . (:. The eigenvalues obtained by the objects are the retention times listed in Tables, 2 and 3 ("," 'recorded in units of knife/knife) and molecular ions (typically cations) VTH+, . ^ )° indicates the HPLC-MS method used in parentheses. 114 201020252

Method B (Agilentll00 Series LC)' It has the following HPLC gradient conditions: Solvent A: 0 · 10 / hydrazine in water / acetonitrile (9:1) phthalic acid solvent B: 0 · 1 % decanoic acid time in acetonitrile ( Minutes) A ( % ) B ( % ) Flow rate (ml / min) 0 90 10 1.7 2.5 0 100 1.7 2.8 0 100 1.7 2.9 90 10 1.7 Column type: Water atlantis dcl8 ; Column length: 20 mm; Inner diameter: 3 mm; particle size: 3 μm; temperature: 40 °C.

Method C ( Thermo HPLC ) 'It has the following HPLC gradient conditions: Solvent A: 0.25% formic acid solvent in water B: 0.025% formic acid in acetonitrile Time (minutes) A ( % ) B ( % ) Flow rate (ml / Minutes) 0 90 10 1.0 0.5 90 10 1.0 4.3 5 95 1.0 5.0 0 100 1.0 7.1 0 100 1.0 7.5 90 10 1.0 9.0 90 10 1.0 Column type: Waters, symmetry C-1 8 ; column length: 5 mm; 115 201020252 Column inner diameter: 4.6 mm; particle size: 3.5 μm; method Thermo HPLC) with the following HPLC gradient conditions: Solvent A: 0.25% formic acid solvent in water B: 0.025% formic acid in acetonitrile time (minutes ) A ( % ) B ( % ) Flow rate (ml / min) 0 90 10 1.3 3.8 0 100 1.3 4.8 0 100 1.3 5.0 90 10 1.3 6.0 90 10 1.3 Column type · · Waters, symmetry C-18; Length: 50 mm; s-column fe: 4.6 mm; particle size: 3 5 μm; characteristic values obtained for each compound are as shown in Tables 1, 2 and 3 ("RT", in minutes) Unit records) and molecular ions (typically cationic MH+). The HpLC_MS method used is indicated in parentheses.

The invention has been described with reference to preferred embodiments and examples thereof, but the scope of the invention is not limited to the specific examples described. It is obvious to those skilled in the art that the invention described above may be modified and modified without departing from the spirit and scope of the invention as defined and limited by the scope of the appended claims. All publications are hereby incorporated by reference in their entirety for all purposes in the extent of the disclosure of the disclosures of 116 201020252

[Simple description of the diagram] None [Main component symbol description

Claims (1)

201020252 VII. Scope of application: 1. A method for preventing and/or controlling fungal infections in plants and/or plant propagation materials, comprising applying to the plant or plant propagation material (〇 compound: Wherein G^G2 and G3 are n and the other two of G, G2 and G3 are CR8, CR1 or CR2' such that when g1 is not N, G1 is CR8; when G2 is not N ' G2 is CR1 When G3 is not N, G3 is CR2; X1 is N or CH; X2 is N or CR5; R1 is: (i) hydrogen, halogen, thiol, lactyl or schwitz, (ii) as appropriate Substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl or optionally substituted alkoxy, (iii) optionally substituted aryl, optionally substituted heteroaryl , optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl, or (iv) -C(0)R10, _C(O)NR10Rn '-C(S )NR10Rn, -C(NOR,0)r丨1, -C(0)〇R10, -OR10, -SR10, -S(0)R10, -S(O)NR,0Rn &gt; .S(O) 2NR10R11 &gt; -S(0)2R10 ' -NR10Rn ' -P(〇)(OR10)(01111) or -〇P(〇)(〇R10)(ORn); 201020252 R2 is: (i) hydrogen, halogen, a hydroxy, cyano or nitro group, (η) optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, (iii) optionally substituted Aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl, or (iv) -C(〇) R10 ' -C(0)NR丨0R丨丨, -C(S)NR]0RU, -C(NOR10)R丨丨, -C(〇)ORj〇, _〇Ri〇, _SRio, _S(〇) R|0, -S(O)NR10R&quot;&gt; -S(O)2NR,0Rn &gt; -S(0)2R10 ^ -NR10Rn &gt; -PiOKOR^KOR11) or _〇P(〇)(〇R丨0) (〇RU); R3 is: (0 hydrogen, hydroxy, cyano or nitro, (ii) optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, ( Il) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl, or (iv -C(0)R12, -C(0)0R12, -OR12, _〇C(0)Ri2, -s(o)2r12 or -NRI2R13; R4 is: (i) hydrogen, halogen, meridine, cyanide Or nitro, (i) a decentralized or substituted alkynyl group, as the case may be substituted, 119 201020252 (Hi) an optionally substituted aryl group, Substituted heteroaryl, optionally substituted cyclic oxime, optionally substituted heterocyclo or optionally substituted cycloalkenyl, or (iv) -C(0)Ru . .C(〇) 〇Ru ^ .C(N〇r14)r15 ^ _〇r14 ^ -SR14 ^ -S(0)NR^r-3 . .S(〇)2Rm ^.NRl4Rl5 . R5 is: (i) Hydrogen, dentate , hydroxy, cyano or nitro, (11) substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl, q (iii) -c(o)rm, _C( 0) 0R ", _ 〇 Rl6, _SRl6' s (〇) r16, -S (0) NR16R17, -S (0) 2R16 or ^ 1116 ft 17; R6 is: (i) hydrogen, halogen, hydroxyl 'B An oxy or cyano group, (11) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or, as appropriate, substituted Cycloalkenyl, or (iii) -C(0)0R18, -SR18, -NR18R19, -C(0)NR18R19, 〇-N = CR20 or -C(,R18)NR19R20; R7 is: (i) hydrogen, Halogen, hydroxy, cyano or nitro, (ii) optionally substituted alkyl, or (iii) -NR2, R22; R8 is: (i) hydrogen, argin, transbasin, gas or jing, 120 201020252 (ii ) Substituted calcined base, or (iii) -NR21R22; R10, R&quot;, R14, R15, R16 and R17 are independently: (i) hydrogen, i, hydroxy, cyano or nitrate And (ii) optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl or optionally substituted alkynyl, or (iii) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted cycloalkenyl; R12 and R13 is independently: (i) hydrogen, halogen, hydroxy, cyano, nitro or _Nr21r22, (ii) optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkenyl Or an optionally substituted alkynyl group, or (iii) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or Optionally substituted cycloalkenyl; Rl8 and R19 are independently: (i) hydrogen, (8) optionally substituted alkyl, optionally substituted alkynyl, '((1)) substituted as appropriate An aryl group, optionally substituted (4), optionally substituted heterocycloalkyl or #It, a substituted cycloalkenyl group, or a (iV)-C(S)R23..C (〇 R23^s〇2R23 121 201020252 - . or c(o)nr23r24 ; ' R20 is: (i) carboxyl, (ii) optionally substituted alkyl or substituted as appropriate Oxy, or (iii) -NR21R22 or -N=CR2IR22; R21 and R22 are independently: (i) hydrogen, (ii) optionally substituted alkyl, optionally substituted alkenyl or © optionally Substituted alkynyl, (iii) optionally substituted aryl 'optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or optionally substituted ring Alkenyl, or (iv) -C(0)〇R25; R23 and R24 are, independently, (i) hydrogen or thiol, (ii) optionally substituted alkyl, optionally substituted alkenyl or © Optionally substituted alkynyl, or (iii) optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl or, as appropriate Substituted cycloalkenyl; and 2 5 R are optionally substituted leukoxyl optionally substituted alkenyl or optionally substituted alkynyl; and 122 201020252 2 depending on the case: independently, (i) R1 And R2, (H) R丨 and R3, r..· R and R3 '( iv) R3 and R5, ( '(Hi) (vn) R5 盥R'f ··, Du ) R5 and inverse 18, u ) R And R, (V11〇R丨4 and R]5 and/or (formation of an optionally substituted aryl-transfer R state containing 5 to 18 ring atoms, substituted by molybdenum, molybdenum, „土, visual a cycloalkyl group, a visually-produced, a w-substituted heterocycloalkyl or a optionally substituted cycloaliphatic group; &quot;brothers or isomers thereof, tautomers, N-oxidation Object or salt Oxide salt). Include N- 2 as the method of applying for the patent scope &quot; It is CR and G3 is N. G 3· If the patent application scope 帛i or method and X2 is CH. The method of any one of claims 1 to 3, wherein R is hydrogen, halogen, cyano, and optionally substituted cK6 is optionally substituted C2.6 olefin Substituted phenyl or c(〇)R〇 substituted by alkyne dimorphism as appropriate; R2 is gas or C, _6 alkyl; R3 is hydrogen, hydroxy, ·c(〇)Rl2, -〇 RI2, _c (1) 沁2, -〇C(0)R12, _s(〇)2Rl2, optionally substituted Ci6 alkyl, optionally substituted C2-6 alkenyl or, as appropriate, C2·6 An alkynyl group, optionally substituted c3_6 cycloalkyl; r4 is a gas, halogen, optionally substituted C2.6 alkynyl, as appropriate, aryl substituted by gemen or optionally substituted heteroaryl; R is a sulphate, a cyano group, a thiol group, a C, _4 haloalkyl group or (3|4 calcined. 123 201020252 R6 is hydrogen or -NRI8r19; A R7 is hydrogen, hydroxy, cyano, NR2lR22 or as appropriate Substituted C 1 -6 alkyl; R 8 is hydrogen, hydroxy, cyano, _NR 2 R22 or optionally substituted CI. 6 alkyl; R is hydrogen, C | 4 alkyl, c 2 4 alkenyl or c 2 4 Alkynyl; R19 is hydrogen, isobutyl, -C(0)r23 or _c(〇)〇r23 R21 and R22 are independently selected from the group consisting of hydrogen, fluorenyl and ethyl; R23 is hydrogen, hydroxy, optionally substituted ei-6 alkyl, optionally substituted c2.6 alkenyl, optionally substituted c3 6 ring An alkyl group or a substituted c4_6 cycloalkenyl group, as in the case of claim 4, wherein the alkyl group, the dilute group, the alkynyl group, the phenyl 'cycloalkyl group, the cyclodecyl group, the aryl group and The substituent selected from the heteroaryl group is selected from the group consisting of methoxy, ethoxy, hydroxy, cyano, _, pyridyl, ethylene oxide, tetrahydrofuran, trimethyl decyl and _c (〇) 〇r, wherein R is hydrogen 'hydrazino or ethyl. 6. The method of any one of claims 1 to 5, wherein ❹ R1 is hydrogen, gas or methyl; R is hydrogen or C|_6 a base; R is hydrogen or _; R and R8 are independently hydrogen, hydroxy or nr21r22; 2 j R and R22 are independently hydrogen, decyl or ethyl. 7) as claimed in items 1 to 6 A method according to any one, wherein R is optionally substituted c丨·6 alkyl group 'optionally substituted 匸 124 201020252 alkenyl or optionally substituted C: 2-6 alkynyl, wherein The substituents selected from the group consisting of cyano, decyl and alkynyl, are optionally selected from the group consisting of cyano, fluorenyl and halogen. The method of any one of claims 1 to 6, wherein R3 is hydrogen , cyanomethyl, aminoethyl, aminopropyl, vinyl, prop-2-enyl, prop-2-ynyl, propane-1,2-dienyl, methoxyindenyl, 2 - Fluorinyl, 2-fluoroethyl, -OCH2C, -OCH2OCH3, -〇CH2CN, /OCH(CH3)CN, -OCH2CH=CH2 or benzyl. The method of any one of claims 1 to 8, wherein R4 is optionally one or three groups independently selected from the group consisting of Cl-4 alkyl, C, .4 haloalkyl and halogen. Substituted phenyl. 10. The method of any one of claims 1 to 8, wherein R4 is phenyl, 3-methylphenyl, 3-trifluorodecylphenyl, 2-fluorophenyl, 3-fluorobenzene Base, 4-n-phenyl, 2,5-difluorophenyl, 3-methyl-4-fluorophenyl, 2,4-di-Itphenyl, 2,6-difluorophenyl or 2,4, 6-difluorophenyl. 11. The method of any one of claims 1 to 10, wherein: R6 is hydrogen or -NHR19; R19 is hydrogen, optionally via a trans group or C!4 alkoxy (which may C alkyl-4-alkyl substituted by a benzyl group, or R19 is -C(〇)r23; R23 is CW4 alkyl, C2-4 alkenyl, C2.4 alkynyl or c3.4 cycloalkyl. The method of any one of claims 1 to 11, wherein R6 is NHC(0)R23, wherein R23 is C|-4 alkyl, cyclopropyl or cyclobutyl. 13. The method of claim 1, wherein 125 201020252 毳X1 is CH and &quot; is CH; is a hydrohalyl or optionally substituted C4 alkyl; R is hydrogen or hydrazine; R2 is hydrazine , Cl. 4 alkyl, C2.4 alkenyl, c2_4 alkynyl or _0RU, wherein R is C丨-4 alkyl, c 崁 岭# &gt;, broad 4 3-6 clothing base or C4.6 ring Alkenyl; is phenyl, which is optionally substituted with at least one substituent selected from halogen and Cw alkyl; R6 is dentate or -Nr18r", wherein R18 is hydrogen, prop-2-enyl or propyl , soil and R is _c(0)r23, wherein R23 is hydrogen, methyl, ethyl, isopropyl, 1-mercapto-f-methyl-1-ethylidene, 丨-mercaptopropyl, 2-dimethyl Ethyl ethyl, propyl ' 1 decyl vinyl, 2 · decyl propylene small alkenyl 'but · 3 - alkenyl, cyclopropyl, decyl cyclopropyl, 1-fluorocyclopropyl or cyclobutyl; R Is hydrogen, gas, fluorine or methyl; and R8 is hydrogen, chloro, decyl or 2-decyloxy-i-ethylamine. 1 4. The method of claim 2, wherein X is CH and X2 is CH; Rl is hydrogen, gas or sulfhydryl; r2 is hydrogen or fluorenyl; R is 虱'cyanoguanidino'propan-2-yl, prop-2-ynyl or benzyl; r4 is 2-fluorophenyl '3_fluorophenyl, 4-fluorophenyl, 4-phenylene, 3-methylphenyl or 3-methyl-4-fluorophenyl; R6 is -NRl8R19, wherein Ri8 is hydrogen and r is 9 Is _c(〇)r23, wherein R is decyl, ethyl, isopropyl, cyclopropyl, cyclobutyl or i-decylcyclopropyl; 126 201020252 R7 is hydrogen, chloro, fluoro or methyl; R8 is hydrogen, chlorine or methyl. 1 5 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Substituted; R2 is hydrogen or halogen; ❹ ❹ R3 is hydrogen, C]-4 alkyl, c3-4 alkenyl, C3-4 alkynyl' wherein the C, _4 alkyl group is optionally cyan or oxo Substituted; R4 is a phenyl group optionally substituted with 1 to 3 halogen atoms; R is a wind, -NH-Cu alkyl group, wherein the alkyl group is optionally subjected to a trans group or an alkoxy group (which Substituted by a hydroxy group), or r6 is -NH-CCCO-Cw alkyl, NH_c(〇)_C3 4 cycloalkyl, _NH C(〇)_C3 * alkenyl or -nh-c(o)-c2- 4 alkynyl; R7 is hydrogen or south; R8 is hydrogen or halogen. 16. The method of claim τ ± 罘i, wherein the compound is one of the compounds set forth in Table I, Table or Table. Π.—A compound of the formula • 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 CR丨3 X2 is CR5 and R5 and r6 are both N'X is Ch, r:n^, TN ...玟 is not 4-fluorostyl; and (1)) The compound of formula (I) is not: 7- Phenyl-6-(pyridyl); W is more than [3,2-c] tillage; 127 201020252 7-phenyl-6-(pyridin-4-yl)-5H-pyrrolo[3,2- d]pyrimidine; 7-phenyl-6-(.pyridin-4-yl)-5H-indolo[2,3-b]pyrazine; 7-(3-chlorophenyl)-6-[2 -(2-Methylthioethylamino)-4-acridinyl]-5H-. Specific ratio of [2,3-b]°; 7-(3-chlorophenyl)-6-(2-azeridin-4-yl)-5H-. More than [2,3-b] tillage; or 7-(4-fluorophenyl)-6-(.pyridin-4-yl)-5H-. More than [3,2-d] pyrimidine. A composition for controlling a fungal infection comprising a compound of the formula (I) as defined in any one of claims 1 to 16 and an agriculturally acceptable carrier or diluent. 19. The composition of claim 18, wherein the composition further comprises at least one active ingredient selected from the group consisting of fungicides, herbicides, insecticides, bactericides, acaricides, nematicides, and / or plant growth