TRISUBSTITUTEDSILYLHETEROARYLOXYQUINOLINES AND ANALOGUES

The present disclosure relates to fungicidal active compounds, more specifically to trisubstitutedsilylphenoxyheterocycles and analogues thereof, processes and, intermediates for their preparation as well as use thereof as fungicidal active compound, particularly in the form of fungicide compositions. The present disclosure also relates to methods for the control of phytopathogenic fungi of plants using these compounds or compositions comprising thereof.

TECHNICAL FIELD

The present disclosure relates to fungicidal active compounds, more specifically to trisubstitutedsilylheteroaryloxyquinolines and analogues thereof, processes and intermediates for their preparation and use thereof as fungicidal active compound, particularly in the form of fungicide compositions. The present disclosure also relates to methods for the control of phytopathogenic fungi of plants using these compounds or compositions comprising thereof.

BACKGROUND

Some aryloxyquinolines are known to exhibit fungicidal activities.

In Japanese patent application JP-2014/124411 and in international patent application WO 2013/002205, certain phenoxyquinolines are generically embraced in a broad disclosure of numerous compounds of the following formula:

wherein D and E represent a 5- to 7-membered ring, X represents O, NH or N—C1-C8-alkyl, B (or Y) represents C or N, and R represents among various groups, an optionally substituted alkoxy group, an optionally disubstituted amino group, an optionally substituted and optionally oxidized alkylsulfanyl group, or a nitro group. However, JP-2014/124411 and WO2013/002205 do not disclose nor suggest providing compounds wherein R represents a substituted silylated group.

In Japanese patent application JP-2014/166991 certain phenoxyquinolines are generically embraced in a broad disclosure of numerous compounds of the following formula:

wherein A represents a 5- to 7-membered ring, D represents a 5- to 7-membered hydrocarbon or heterocycle ring, X represents O, S, an unsubstituted or substituted carbon or nitrogen atom, Z and B independently represent C or N, and R represents a group CR1R2R3, C═O—R3, CR3═CRaRb, CR3N═Rc, C6-C10aryl, alkynyl or CN.

In international patent application WO 2011/081174 certain phenoxyquinolines are generically embraced in a broad disclosure of numerous compounds of the following formula:

wherein A and D represent a 5- to 7-membered hydrocarbon or heterocycle ring, X represents O, S, S(O), S(O)2, an optionally substituted C, or an optionally substituted N, Y and Z independently represent C or N, and R represents an optionally substituted alkyl group, an optionally substituted C6-C10-aryl group, or a cyano group. However, WO 2011/081174 does not disclose nor suggest providing compounds wherein R represents a substituted silylated group.

In international patent application WO 2012/161071 certain phenoxyquinolines are generically embraced in a broad disclosure of numerous compounds of the following formula:

wherein D represents a 5- to 7-membered ring, A1, A2, A3and A4independently represent C or N provided at least one of Anis N, and R represents an optionally substituted alkyl group or a cyano group. However, WO 2012/161071 does not disclose nor suggest providing compounds wherein R represents a substituted silylated group.

In international patent application WO 2013/058256 certain phenoxyquinolines are generically embraced in a broad disclosure of numerous compounds of the following formula:

wherein D and E represent a 5- to 7-membered hydrocarbon or heterocycle ring, X represents O, S, C(O) or CH(OH), B represents C or N, and Cy represents an optionally substituted oxiranyl, or an optionally substituted 5- or 6-membered heterocyclyl group. However, WO 2013/058256 does not disclose nor suggest providing compounds wherein Cy represents a substituted silylated cycle.

In international patent application WO 2006/031631 certain 3-pyridyl derivatives are generically embraced in a broad disclosure of numerous compounds of the following formula:

wherein R1represents an aryl which is optionally substituted or a heteroaryl which is optionally substituted, R2represents a heteroaryl which is optionally substituted, R3represents an alkyl, an aryl which is optionally substituted, a heteroaryl which is optionally substitutedor an alkylsilyl andR4represents hydrogen atom. However, WO 2006/031631 does not disclose nor suggest providing compounds wherein R2represents a fused bicyclic heterocyclyl ring.

However, since the ecological and economic demands made on fungicide active compounds are increasing constantly, for example with respect to activity spectrum, toxicity, selectivity, application rate, formation of residues and favourable manufacture, and since there can also be problems associated with resistances, there is a constant need to develop novel fungicidal compounds and compositions which have advantages over the known compounds and compositions at least in some areas.

DETAILED DESCRIPTION

Accordingly, the present invention provides trisubstitutedsilylheteroaryloxyquinolines and analogues thereof as described herein below that may be used fungicides.

Active Ingredients

The present invention provides compounds of formula (I)

whereinA represents a quinolin-3-yl ring or a quinoxalin-2-yl ring with Q1is C or A represents a 1H-benzimidazol-1-yl ring with Q1is N;B represents a 5- or 6-membered heterocyclyl ring comprising 1, 2 or 3 heteroatoms independently selected in the list consisting of N, O and S;Z is selected from the group consisting of hydrogen atom, halogen atom, C1-C8-alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkenyl, C2-C8-halogenoalkenyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkynyl, C2-C8-halogenoalkynyl comprising up to 9 halogen atoms that can be the same or different, C3-C7-cycloalkyl, C4-C7-cycloalkenyl, hydroxyl, C1-C8-alkoxy, C1-C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different, aryl, heterocyclyl, formyl, C1-C8-alkylcarbonyl, (hydroxyimino)C1-C8-alkyl, (C1-C8-alkoxyimino)C1-C8-alkyl, carboxyl, C1-C8-alkoxycarbonyl, carbamoyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, amino, C1-C8-alkylamino, di-C1-C8-alkylamino, sulfanyl, C1-C8-alkylsulfanyl, C1-C8-alkylsulfinyl, C1-C8-alkylsulfonyl, C1-C6-trialkylsilyl, cyano and nitro,wherein said C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl and C1-C8-alkoxy may be substituted with one or more Zasubstituents and wherein said C3-C7-cycloalkyl, C4-C7-cycloalkenyl, aryl and heterocyclyl may be substituted with one or more Zbsubstituents;n represents 0, 1, 2 or 3;p represents 0, 1, 2, 3, 4 or 5;L represents O, S, SO, SO2, CR4R5or NR6whereinR4and R5are independently selected from the group consisting of hydrogen atom, halogen atom, hydroxyl, C1-C8alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C1-C8-alkoxy and C1-C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different, or they may form together with the carbon atom to which they are linked a carbonyl group;R6is selected from the group consisting of hydrogen atom, C1-C8-alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkenyl, C2-C8-halogenoalkenyl comprising up to 9 halogen atoms that can be the same or different, C3-C8-alkynyl, C3-C8-halogenoalkynyl comprising up to 9 halogen atoms that can be the same or different, C3-C7-cycloalkyl, C3-C7-halogenocycloalkyl comprising up to 9 halogen atoms that can be the same or different, C3-C7-cycloalkyl-C1-C8-alkyl, formyl, C1-C8-alkylcarbonyl, C1-C8-halogenoalkylcarbonyl comprising up to 9 halogen atoms that can be the same or different, C1-C8-alkoxycarbonyl, C1-C8-halogenoalkoxycarbonyl comprising up to 9 halogen atoms that can be the same or different, C1-C8-alkylsulfonyl, C1-C8-halogenoalkylsulfonyl comprising up to 9 halogen atoms that can be the same or different, aryl-C1-C8-alkyl and phenylsulfonyl, wherein said C1-C8-alkyl, C2-C8-alkenyl and C3-C8-alkynyl may be substituted with one or more R6asubstituents and wherein said C3-C7-cycloalkyl, C3-C7-cycloalkyl-C1-C8-alkyl, aryl-C1-C8-alkyl and phenylsulfonyl may be substituted with one or more R6bsubstituents;X is independently selected from the group consisting of halogen atom, C1-C8-alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkenyl, C2-C8-halogenoalkenyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkynyl, C2-C8-halogenoalkynyl comprising up to 9 halogen atoms that can be the same or different, C3-C7-cycloalkyl, C4-C7-cycloalkenyl, hydroxyl, C1-C8-alkoxy, C1-C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different, C1-C6-trialkylsilyl, cyano and nitro,wherein said C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl and C1-C8-alkoxy may be substituted with one or more Xasubstituents and said C3-C7-cycloalkyl and C4-C7-cycloalkenyl may be substituted with one or more Xbsubstituents;Y is independently selected from the group consisting of halogen atom, C1-C8-alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkenyl, C2-C8-halogenoalkenyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkynyl, C2-C8-halogenoalkynyl comprising up to 9 halogen atoms that can be the same or different, C3-C7-cycloalkyl, C4-C7-cycloalkenyl, hydroxyl, C1-C8-alkoxy, C1-C8-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different, aryl, heterocyclyl, formyl, C1-C8-alkylcarbonyl, (hydroxyimino)C1-C8-alkyl, (C1-C8-alkoxyimino)C1-C8-alkyl, carboxyl, C1-C8-alkoxycarbonyl, carbamoyl, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, amino, C1-C8-alkylamino, di-C1-C8-alkylamino, sulfanyl, C1-C8-alkylsulfanyl, C1-C8-alkylsulfinyl, C1-C8-alkylsulfonyl, C1-C6-trialkylsilyl, cyano and nitro,wherein said C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl and C1-C8-alkoxy may be substituted with one or more Yasubstituents and wherein said C3-C7-cycloalkyl, C4-C7-cycloalkenyl, aryl and heterocyclyl may be substituted with one or more Ybsubstituents;R1is selected from the group consisting of C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C7-cycloalkyl, C4-C7-cycloalkenyl, aryl and heterocyclyl, wherein said C1-C8-alkyl, C2-C8-alkenyl and C2-C8-alkynyl may be substituted with one or moreR1asubstituents and wherein said C3-C7-cycloalkyl, C4-C7-cycloalkenyl, aryl and heterocyclyl may be substituted with one or more R1bsubstituents;R2is selected from the group consisting of hydroxyl, C1-C8-alkoxy, C1-C8-alkyl, C2-C8-alkenyl, C2-C8-alkynyl, C3-C7-cycloalkyl, C4-C7-cycloalkenyl, aryl and heterocyclyl,wherein said C1-C8-alkoxy, C1-C8-alkyl, C2-C8-alkenyl and C2-C8-alkynyl may be substituted with one or more R2asubstituents and wherein said C3-C7-cycloalkyl, C4-C7-cycloalkenyl, aryl and heterocyclyl may be substituted with one or more R2bsubstituents;when R1and R2represent a C1-C8alkyl or a C2-C8alkenyl, they can form, together with the silicon atom to which they are linked, a C3-C8-silacycloalkyl ring or a C4-C8-silacycloalkenyl ring,wherein said C3-C8-silacycloalkyl ring or C4-C8-silacycloalkenyl ring may be substituted with one or more R1bsubstituents;R3is selected from the group consisting of hydrogen atom, halogen atom, C1-C8-alkyl, C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C2-C8-alkenyl, C2-C8-alkynyl, C3-C7-cycloalkyl, C4-C7-cycloalkenyl, hydroxyl, C1-C8-alkoxy, aryl, aryl-C1-C8-alkyl, heterocyclyl, heterocyclyl-C1-C8-alkyl, hydroxy-C1-C8-alkyl, C1-C8-alkoxy-C1-C8-alkyl, C1-C8-alkylcarbonyloxy-C1-C8-alkyl, aryloxy-C1-C8-alkyl, heterocyclyloxy-C1-C8-alkyl, amino-C1-C8-alkyl, C1-C8-alkylamino-C1-C8-alkyl, di-C1-C8-alkylamino-C1-C8-alkyl, arylamino-C1-C8-alkyl, di-arylamino-C1-C8-alkyl, heterocyclylamino-C1-C8-alkyl, C1-C8-alkylcarbonylamino-C1-C8-alkyl, C1-C8-alkoxycarbonylamino-C1-C8-alkyl, C1-C8-alkylsulfanyl-C1-C8-alkyl, C1-C8-alkylsulfinyl-C1-C8-alkyl, C1-C8-alkylsulfonyl-C1-C8-alkyl and cyano-C1-C8-alkyl,wherein said C1-C8-alkyl, C2-C8-alkenyl and C2-C8-alkynyl may be substituted with one or more R3asubstituents and wherein said C3-C7-cycloalkyl, C4-C7-cycloalkenyl, aryl, aryl-C1-C8-alkyl, heterocyclyl, heterocyclyl-C1-C8-alkyl, aryloxy-C1-C8-alkyl and heterocyclyloxy-C1-C8-alkyl may be substituted with one or more R3bsubstituents;R3and X, when said X is vicinal to SiR1R2R3, may form, together with the silicon and carbon atoms to which they are respectively attached, a 5-, 6- or 7-membered, partially saturated, heterocycle,wherein said 5-, 6- or 7-membered, partially saturated, heterocycle may be substituted with one or more R3bsubstituents;when R2represents a C1-C8-alkoxy and R3represents a C1-C8-alkoxy or a C1-C8alkyl, they can form, together with the silicon atom to which they are linked a 5-, 6- or 7-membered heterocycle, wherein said 5-, 6- or 7-membered heterocycle may be substituted with one or more R2bsubstituents;Za, R1a, R2a, R3a, R6a, Xaand Yaare independently selected from the group consisting of nitro, hydroxyl, cyano, carboxyl, amino, sulfanyl, pentafluoro-λ6-sulfanyl, formyl, carbamoyl, carbamate, C3-C7-cycloalkyl, C3-C8-halogenocycloalkyl having 1 to 5 halogen atoms, C1-C8-alkylamino, di-C1-C8-alkylamino, C1-C8-alkoxy, C1-C8-halogenoalkoxy having 1 to 5 halogen atoms, C1-C8-alkylsulfanyl, C1-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms, C1-C8-alkylcarbonyl, C1-C8-halogenoalkylcarbonyl having 1 to 5 halogen atoms, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8-alkoxycarbonyl, C1-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms, C1-C8-alkylcarbonyloxy, C1-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms, C1-C8-alkylcarbonylamino, C1-C8-halogenoalkylcarbonylamino having 1 to 5 halogen atoms, C1-C8-alkylsulfinyl, C1-C8-halogenoalkylsulfinyl having 1 to 5 halogen atoms, C1-C8-alkylsulfonyl and C1-C8-halogeno-alkyl-sulfonyl having 1 to 5 halogen atoms;Zb, R1b, R2b, R3b, R6b, Xband Ybare independently selected from the group consisting of halogen atom, nitro, hydroxyl, cyano, carboxyl, amino, sulfanyl, pentafluoro-λ6-sulfanyl, formyl, carbamoyl, carbamate, C1-C8-alkyl, C3-C7-cycloalkyl, C1-C8-halogenoalkyl having 1 to 5 halogen atoms, C3-C8-halogenocycloalkyl having 1 to 5 halogen atoms, C2-C8-alkenyl, C2-C8-alkynyl, C1-C8-alkylamino, di-C1-C8-alkylamino, C1-C8-alkoxy, C1-C8-halogenoalkoxy having 1 to 5 halogen atoms, C1-C8-alkylsulfanyl, C1-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms, C1-C8-alkylcarbonyl, C1-C8-halogenoalkylcarbonyl having 1 to 5 halogen atoms, C1-C8-alkylcarbamoyl, di-C1-C8-alkylcarbamoyl, C1-C8-alkoxycarbonyl, C1-C8-halogenoalkoxycarbonyl having 1 to 5 halogen atoms, C1-C8-alkylcarbonyloxy, C1-C8-halogenoalkylcarbonyloxy having 1 to 5 halogen atoms, C1-C8-alkylcarbonylamino, C1-C8-halogenoalkylcarbonylamino having 1 to 5 halogen atoms, C1-C8-alkylsulfanyl, C1-C8-halogenoalkylsulfanyl having 1 to 5 halogen atoms, C1-C8-alkylsulfinyl, C1-C8-halogenoalkylsulfinyl having 1 to 5 halogen atoms, C1-C8-alkylsulfonyl and C1-C8-halogeno-alkyl-sulfonyl having 1 to 5 halogen atoms;

as well as their salts, N-oxides, metal complexes, metalloid complexes and optically active isomers or geometric isomers.

As used herein, the expression “one or more substituents” refers to a number of substituents that ranges from one to the maximum number of substituents possible based on the number of available bonding sites, provided that the conditions of stability and chemical feasibility are met.

As used herein, halogen means fluorine, chlorine, bromine or iodine; formyl means —CH(═O); carboxyl means —C(═O)OH; carbonyl means —C(═O)—; carbamoyl means —C(═O)NH2; N-hydroxycarbamoyl means —C(═O)NHOH; triflyl means —SO2—CF3; SO represents a sulfoxide group; SO2represents a sulfone group; heteroatom means sulfur, nitrogen or oxygen; methylene means the diradical —CH2—; aryl typically means phenyl or naphthyl; unless provided differently, heterocyclyl means a 5- to 7-membered ring, preferably a 5- to 6-membered ring, which may be saturated, partially saturated or unsaturated, comprising from 1 to 4 heteroatoms independently selected in the list consisting of N, O, S. The term “heterocyclyl” as used herein encompasses heteroaryl.

The term “membered” as used herein in the expression “5- to 7-membered ring” designates the number of skeletal atoms that constitutes the ring.

As used herein, an alkyl group, an alkenyl group and an alkynyl group as well as moieties containing these terms, can be linear or branched.

When an amino group or the amino moiety of any other amino-containing group is substituted by two substituents that can be the same or different, the two substituents together with the nitrogen atom to which they are linked can form a heterocyclyl group, preferably a 5- to 7-membered heterocyclyl group, that can be substituted or that can include other hetero atoms, for example a morpholino group or piperidinyl group.

Any of the compounds of the present invention can exist in one or more optical or chiral isomer forms depending on the number of asymmetric centres in the compound. The invention thus relates equally to all optical isomers and racemic or scalemic mixtures thereof (the term “scalemic” denotes a mixture of enantiomers in different proportions) and to mixtures of all possible stereoisomers, in all proportions. The diastereoisomers and/or the optical isomers can be separated according to methods which are known per se by the man ordinary skilled in the art.

Any of the compounds of the present invention can also exist in one or more geometric isomer forms depending on the number of double bonds in the compound. The invention thus relates equally to all geometric isomers and to all possible mixtures, in all proportions. The geometric isomers can be separated according to general methods, which are known per se by the man ordinary skilled in the art.

Any of the compounds of the present invention can also exist in one or more geometric isomer forms depending on the relative position (syn/anti or cis/trans) of the substituents of the chain or ring. The invention thus relates equally to all syn/anti (or cis/trans) isomers and to all possible syn/anti (or cis/trans) mixtures, in all proportions. The syn/anti (or cis/trans) isomers can be separated according to general methods, which are known per se by the man ordinary skilled in the art.

When a compound of the invention can be present in tautomeric form, the invention also encompasses any tautomeric forms of such compound, even when this is not expressly mentioned.

Compounds of formula (I) are herein referred to as “active ingredient(s)”.

In the above formula (I), Z is preferably selected from the group consisting of hydrogen atom, halogen atom, hydroxyl, C1-C6-alkyl, C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C1-C6-alkoxy, C1-C6-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different and cyano, more preferably Z is a hydrogen atom or a C1-C6-alkyl, even more preferably Z is a hydrogen atom or a methyl group.

In the above formula (I), n is preferably 0 or 1.

In the above formula (I), p is preferably 0, 1, 2 or 3, more preferably p is 0, 1 or 2.

In the above formula (I), L is preferably O, NH or CH2, more preferably O.

In the above formula (I), X is preferably independently a halogen atom, a C1-C6-alkyl group, a C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, a C1-C6-alkoxy, a C1-C6-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different or a cyano, more preferably X is independently a chlorine atom, a fluorine atom, a methyl group or a trifluoromethyl group.

In the above formula (I), Y is preferably independently selected from the group consisting of halogen atom, C1-C6-alkyl, C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C1-C6-alkoxy, C1-C6-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different and cyano, more preferably Y is independently selected from the group consisting of halogen atom, C1-C6-alkyl and C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, even more preferably Y is independently a fluorine atom, a chlorine atom, a methyl group or a trifluoromethyl group.

In the above formula (I), R1is preferably a C1-C6-alkyl, more preferably a methyl group.

In the above formula (I), R2is preferably a C1-C6-alkyl, more preferably a methyl group.

In the above formula (I), R3is preferably selected from the group consisting of hydroxy, C1-C6-alkyl, C2-C6-alkenyl, C1-C6-alkoxy, aryl that may be substituted as disclosed herein above (e.g. phenyl and C1-C6-alkyloxy-phenyl), aryl-C1-C6-alkyl, heterocyclyl and heterocyclyl-C1-C6-alkyl, more preferably R3is selected from the group consisting of hydroxy, C1-C6-alkyl, C2-C6-alkenyl, C1-C6-alkoxy, aryl that may be substituted as disclosed herein above, aryl-C1-C6-alkyl and heterocyclyl, even more preferably R3is a hydroxy, a methyl group, a vinyl group, a phenyl group, a thienyl group or a benzyl group.

In the above formula (I), A is preferably a quinolin-3-yl ring or a quinoxalin-2-yl ring (Q1is a carbon atom).

In the above formula (I), B is preferably selected from the group consisting of:

wherein:R1, R2and R3are as disclosed above;Q4is O, S or NY7with Y7being a hydrogen atom or a C1-C8-alkyl;X1, X2and X3are independently a hydrogen atom or X as disclosed above, preferably, X1, X2and X3are independently selected from the group consisting of hydrogen atom, halogen atom, C1-C6-alkyl, C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C1-C6-alkoxy, C1-C6-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different and cyano, more preferably X1, X2and X3are independently selected from the group consisting of hydrogen atom, halogen atom, C1-C6-alkyl and C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, even more preferably X1, X2and X3are independently a hydrogen atom, a fluorine atom, a chlorine atom, a methyl group or a trifluoromethyl group.

In a preferred embodiment, compounds according to the invention are compounds of formula (I) wherein:A is selected from the group consisting of a quinolin-3-yl ring or a quinoxalin-2-yl ring (Q1is C) wherein:p is as disclosed above, preferably p is 0, 1 or 2;Y is independently as disclosed above, preferably, Y is independently selected from the group consisting of halogen atom, C1-C6-alkyl, C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C1-C6-alkoxy, C1-C6-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different and cyano, more preferably Y is independently selected from the group consisting of halogen atom, C1-C6-alkyl and C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, even more preferably Y is independently a fluorine atom, a chlorine atom, a methyl group or a trifluoromethyl group;Z is as disclosed above, preferably Z is selected from the group consisting of hydrogen atom, halogen atom, hydroxyl, C1-C6-alkyl, C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C1-C6-alkoxy, C1-C6-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different and cyano, more preferably Z is a hydrogen atom or a C1-C6-alkyl, even more preferably Z is a hydrogen atom or a methyl group;B is selected from the group consisting of:

preferably B is selected from the group consisting of B2, B3, B4, B5, B8and B10,

wherein:R1, R2and R3are as disclosed above, preferably R1is a C1-C6-alkyl, more preferably a methyl group, preferably R2is a C1-C6-alkyl, more preferably a methyl group, preferably R3is selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C1-C6-alkoxy, C3-C7-cycloalkyl, aryl that may be substituted as disclosed above, aryl-C1-C6-alkyl, heterocyclyl, heterocyclyl-C1-C6-alkyl and hydroxyl, more preferably R3is selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C1-C6-alkoxy, aryl that may be substituted as disclosed above, aryl-C1-C6-alkyl, heterocyclyl and hydroxyl, even more preferably R3is a hydrogen atom, a hydroxyl, a methyl group, a vinyl group, a phenyl group, a 2-thienyl group, or a benzyl group;Q4is O, S or NY7with Y7being a hydrogen atom or a C1-C8-alkyl;X1, X2and X3are independently a hydrogen atom orX as disclosed above, preferably, X1, X2and X3are independently selected from the group consisting of hydrogen atom, halogen atom, C1-C6-alkyl, C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, C1-C6-alkoxy, C1-C6-halogenoalkoxy comprising up to 9 halogen atoms that can be the same or different and cyano, more preferably X1, X2and X3are independently selected from the group consisting of hydrogen atom, halogen atom, C1-C6-alkyl and C1-C6-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different, even more preferably X1, X2and X3are independently a hydrogen atom, a fluorine atom, a chlorine atom, methyl group or a trifluoromethyl group; andL is as disclosed above, preferably L is O, NH or CH2, more preferably L is O.

In the preferred embodiment disclosed herein above (wherein A is quinolin-3-yl ring or a quinoxalin-2-yl ring), some preferred compounds are compounds of formula (I) wherein B is B2, B2being as disclosed herein above.

In the preferred embodiment disclosed herein above, some other preferred compounds are compounds of formula (I) wherein B is B3, B3being as disclosed herein above.

In the preferred embodiment disclosed herein above, some other preferred compounds are compounds of formula (I) wherein B is B4, B4being as disclosed herein above.

In the preferred embodiment disclosed herein above, some other preferred compounds are compounds of formula (I) wherein B is B5, B5being as disclosed herein above.

The above mentioned preferences with regard to the substituents of the compounds according to the invention can be combined in various manners. These combinations of preferred features thus provide sub-classes of compounds according to the invention. Examples of such sub-classes of preferred compounds according to the invention are:preferred features of A with one or more preferred features of B, L, R1, R2, R3, n, p, X, Y and Z;preferred features of B with one or more preferred features of A, L, R1, R2, R3, n, p, X, Y and Z;preferred features of L with one or more preferred features of A, B, R1, R2, R3, n, p, X, Y and Z;preferred features of R1with one or more preferred features of A, B, L, R2, R3, n, p, X, Y and Z;preferred features of R2with one or more preferred features of A, B, L, R1, R3, n, p, X, Y and Z;preferred features of R3with one or more preferred features of A, B, L, R1, R2, n, p, X, Y and Z;preferred features of n with one or more preferred features of A, B, L, R1, R2, R3, p, X, Y and Z;preferred features of p with one or more preferred features of A, B, L, R1, R2, R3, n, X, Y and Z;preferred features of X with one or more preferred features of A, B, L, R1, R2, R3, n, p, Y and Z;preferred features of Y with one or more preferred features of A, B, L, R1, R2, R3, n, p, X and Z;preferred features of Z with one or more preferred features of A, B, L, R1, R2, R3, n, p, X and Y.

In these combinations of preferred features of the substituents of the compounds according to the invention, the said preferred features can also be selected among the more preferred features of each of A, B, L, R1, R2, R3, n, p, X, Y and Z so as to form most preferred subclasses of compounds according to the invention.

Processes for the Preparation of the Active Compounds

The present invention also relates to processes for the preparation of compounds of formula (I).

Compounds of formula (I) as herein-defined can be prepared by a process P1 which comprises the step of reacting a halogenoaryl of formula (II) or one of its salts:

wherein A, B, Q1, L, n, p, X, Y and Z are as herein-defined and U1represents a chlorine atom, a bromine atom, an iodine atom, a mesyl group, a tosyl group or a triflyl group, with a disilyl derivative of formula (IIIa):

Process P1 can be performed in the presence of a transition metal catalyst such as palladium and if appropriate in the presence of a phosphine ligand or a N-heterocyclic carbene ligand, if appropriate in the presence of a base and if appropriate in the presence of a solvent according to known processes (Organic Letters (2003), 5, 3483, Organic Letters (2007), 9, 3785 and cited references therein).

Derivatives of formula (II) wherein wherein A, B, Q1, L, n, p, X, Y and Z are as herein-defined and U1represents a chlorine atom, a bromine atom or an iodine atom, can be prepared by diazotation of an aniline of formula (IV) or one of its salts:

wherein A, B, Q1, L, n, p, X, Y and Z are as herein-defined, according to known processes (Patai's Chemistry of Functional Groups—Amino, Nitroso, Nitro and Related Groups—1996).

Derivatives of formula (II) can also be prepared by aromatic nucleophilic substitution according to known processes (Journal of Heterocyclic Chemistry (2008), 45, 1199 and Synthetic Communications (1999), 29, 1393).

Derivatives of formula (II) can also be prepared from compounds of formula (VIII) by condensation of the corresponding ortho-substituted [thio]phenols or anilines according to known processes (US-2012/289702).

Derivatives of formula (II) can also be prepared by process P6 described below.

Anilines of formula (IV) wherein wherein A, B, Q1, L, n, p, X, Y and Z are as herein-defined can be prepared by reduction of a nitro group of formula (V) or one of its salts:

wherein A, B, Q1, L, n, p, X, Y and Z are as herein-defined according to known processes (Patai's Chemistry of Functional Groups—Amino, Nitroso, Nitro and Related Groups—1996).

Disilyl derivatives of formula (IIIa) are known or can be prepared by known processes.

Compounds of formula (I) wherein R3represents a hydroxyl can be prepared from compounds of formula (I) wherein R3represents an unsubstituted or substituted C1-C6-alkoxy (themselves prepared by process P1) by an acidic hydrolysis according to known processes (Organic Letters (2003), 5, 3483) Compounds of formula (I) wherein R3represents a fluorine atom can be prepared from compounds of formula (I) wherein R3represents an unsubstituted or substituted C1-C6-alkoxy (themselves prepared by process P1) by known processes (Synlett (2012), 23, 1064 and cited references therein) or can be prepared from compounds of formula (I) wherein R3represents a hydroxyl by known processes (EP1908472)

Process P1 can be carried out in the presence of a catalyst, such as a metal salt or complex. Suitable metal derivatives for this purpose are transition metal catalysts such as palladium. Suitable metal salts or complexes for this purpose are for example, palladium chloride, palladium acetate, tetrakis(triphenylphosphine)palladium(0), bis(dibenzylideneacetone)palladium(0), tris(dibenzylideneacetone)dipalladium(0), bis(triphenylphosphine)palladium(II) dichloride, [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), bis(cinnamyl)dichlorodipalladium(II), bis(allyl)-dichlorodipalladium(II) or [1,1′-Bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II).

It is also advantageous to choose the appropriate catalyst and/or ligand from commercial catalogues such as “Metal Catalysts for Organic Synthesis” by Strem Chemicals or “Phosphorous Ligands and Compounds” by Strem Chemicals.

Suitable bases for carrying out process P1 can be inorganic and organic bases which are customary for such reactions. Preference is given to using alkaline earth metal or alkali metal hydroxides, such as sodium hydroxide, calcium hydroxide, potassium hydroxide or other ammonium hydroxide derivatives alkaline earth metal, alkali metal or ammonium fluorides such as potassium fluoride, caesium fluoride or tetrabutylammonium fluoride; alkaline earth metal or alkali metal carbonates, such as sodium carbonate, potassium carbonate, potassium bicarbonate, sodium bicarbonate or caesium carbonate; alkali metal or alkaline earth metal acetates, such as sodium acetate, lithium acetate, potassium acetate or calcium acetate; alkali metal or alkaline earth metal phosphate, such as tripotassium phosphate alkali; alkali metal alcoholates, such as potassium tert-butoxide or sodium tert-butoxide; tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dicyclohexylmethylamine, N,N-diisopropylethylamine, N-methylpiperidine, N,N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU); and also aromatic bases, such as pyridine, picolines, lutidines or collidines.

It can also be advantageous to carry out process P1 with a co-solvent such as water or an alcohol such as methanol, ethanol, propanol, isopropanol or tert-butanol.

Process P1 may be performed in an inert atmosphere such as argon or nitrogen atmosphere. When carrying out process P1, 1 mole or an excess of compound of formula (III) and from 1 to 5 moles of base and from 0.01 to 20 mole percent of a palladium complex can be employed per mole of compound of formula (II). It is also possible to employ the reaction components in other ratios. Work-up is carried out by known methods.

Compounds of formula (I) as herein-defined can be prepared by a process P2 which comprises the step of reacting a compound of formula (VI) or one of its salts:

wherein A, B, Q1, L, n, p, X, Y and Z are as herein-defined and M represents an alkali metal such as lithium that can be complexed by 1 to 2 ligands or a halogenomagnesium that can be complexed by 1 to 2 ligands, with a silyl derivative of formula (IIIb) or a silyl derivative of formula (IIIc):

wherein R1, R2and R3are as herein-defined and U2represents a chlorine atom, a bromine atom, an iodine atom or a C1-C6-alkoxy.

A compound of formula (VI) can be obtained from a halogenoaryl derivative of formula (II) by the reaction with magnesium metal or lithium metal; or by halogen/metal exchange using an alkyllithium reagent or a Grignard reagent or a manufactured complex prepared from an alkyllithium reagent or a Grignard reagent preferably under anhydrous conditions. Optionally lithium chloride can be used in pre-formed combination with these reagents.

Examples of alkyllithium reagents used in the lithiation process include methyllithium, phenyllithium, n-butyllithium, sec-butyllithium, iso-butyllithium, tert-butyllithium, and the like.

Examples of Grignard reagents used in the magnesium complexation process include methylmagnesium chloride, ethylmagnesium chloride, n-butylmagnesium chloride, iso-propylmagnesium chloride, chloro-(2,2,6,6-tetramethyl-1-piperidyl)magnesium and the like. A manufactured complex prepared from n-butylmagnesium chloride and n-butyllithium may also be used.

Examples of ligands used in the lithiation process or magnesium complexation process include tetramethylethylenediamine, hexamethylphosphotriamide, (+) or (−)-sparteine or 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone.

A solvent used in the lithiation or magnesium complexation is not particularly limited as long as it forms an anhydrous reaction system without dissolving the compound to react therewith or exhibit any particular interaction therewith. Preference is given to using non-halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, pentane, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, decalin, ISOPAR (registered trademark) E or ISOPAR (registered trademark) G; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxyethane or 1,2-diethoxyethane; and a mixture thereof.

The lithiation or magnesium complexation may be performed in an inert atmosphere and prepared at a temperature of 0° C. to −78° C.

Alternatively, a compound of formula (VI) can be prepared from a compound of formula (VII) or one of its salts:

by reaction with a base such as n-butyllithium, lithium di-isopropylamine, lithium tetramethylpiperidide, lithium bis(trimethylsilyl)amine, methyllithium or chloro-(2,2,6,6-tetramethyl-1-piperidyl)magnesium and the like, preferably under anhydrous conditions. Optionally lithium chloride can be used in pre-formed combination with these reagents.

The solvent used in the reaction of compounds (VII) with a base is not particularly limited as long as it forms an anhydrous reaction system without dissolving the compound to react therewith or exhibit any particular interaction therewith. Preference is given to using non-halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, pentane, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, decalin, ISOPAR (registered trademark) E or ISOPAR (registered trademark) G; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxyethane or 1,2-diethoxyethane; and a mixture thereof.

The reaction may be performed in an inert atmosphere and prepared at a temperature of 0° C. to −78° C.

Compounds of formula (VII) are known and can be prepared by known processes (Organic Letters (2012), 14, 173, Bioorganic & Medicinal Chemistry, 19, 939 and cited references therein).

Silyl derivatives of formula (Illib) and (lllc) are known or can be prepared by known processes. Compounds of formula (I) wherein R3represents a hydroxyl can also be prepared from compounds of formula (I) wherein R3represents an hydrogen atom (themselves prepared by process P2) by known processes (Chemistry—A European Journal (2012), 18, 9789, WO-2013/058825 and EP1908472).

Suitable solvents for carrying out process P2 are not particularly limited as long as it forms an anhydrous reaction system without dissolving the compound to react therewith or exhibit any particular interaction therewith. Preference is given to using non-halogenated aliphatic, alicyclic or aromatic hydrocarbons, such as petroleum ether, pentane, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene, decalin, ISOPAR (registered trademark) E or ISOPAR (registered trademark) G; ethers, such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dimethoxyethane or 1,2-diethoxyethane or a mixture thereof.

Process P2 may be performed in an inert atmosphere. When carrying out process P2, 1 mole or an excess of compound of formula (IIIb) or compound of formula (IIIc) can be employed per mole of compound of formula (VII). It is also possible to employ the reaction components in other ratios. Work-up is carried out by known methods.

Compounds of formula (I) wherein Q1represent C can be prepared by a process P3 which comprises the step of reacting a compound of formula (VIII) or one of its salts with a compound of formula (IX) as illustrated by the following reaction scheme:

wherein L represents O, S or NR6U3represents a chlorine atom, a bromine atom, an iodine atom, a mesyl group, a tosyl group or a triflyl group;R1and R2independently represent a C1-C8-alkyl, a C2-C8-alkenyl, a C3-C7-cycloalkyl, an aryl or a heterocyclyl; andR3represents a hydrogen atom, a C1-C8-alkyl; a C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; a C2-C8-alkenyl; a C2-C8-alkynyl; a C3-C7-cycloalkyl; a C4-C7-cycloalkenyl; an aryl; an aryl-C1-C8-alkyl; a heterocyclyl; a heterocyclyl-C1-C8-alkyl; a hydroxy-C1-C8-alkyl; a C1-C8-alkoxy-C1-C8-alkyl; a C1-C8-alkylcarbonyloxy-C1-C8-alkyl; an aryloxy-C1-C8-alkyl; a heterocyclyloxy-C1-C8-alkyl; an amino-C1-C8-alkyl; an C1-C8-alkylamino-C1-C8-alkyl; a di-C1-C8-alkylamino-C1-C8-alkyl; an arylamino-C1-C8-alkyl; a di-arylamino-C1-C8-alkyl; a heterocyclylamino-C1-C8-alkyl; a C1-C8-alkylcarbonylamino-C1-C8-alkyl; a C1-C8-alkoxycarbonylamino-C1-C8-alkyl; a C1-C8-alkylsulfanyl-C1-C8-alkyl; a C1-C8-alkylsulfinyl-C1-C8-alkyl; a C1-C8-alkylsulfonyl-C1-C8-alkyl; or a cyano-C1-C8-alkyl; andA, B, n, p, X, Y, R6and Z are as herein-defined.

It is to be understood that any of said R1, R2and R3may be substituted as disclosed in connection with R1, R2and R3of compounds of formula (I).

Compounds of formula (IX) are commercially available or can be prepared by well known processes.

Process P3 can be performed in the presence of a transition metal catalyst such as palladium and if appropriate in the presence of a phosphine ligand or a N-heterocyclic carbene ligand; or copper and if appropriate in the presence of a ligand; and if appropriate in the presence of a base and if appropriate in the presence of a solvent according to known processes (Organic Letters (2012), 14, 170, Organic Letters (2002), 4, 1623 and cited references therein).

Suitable palladium-based catalyst can be as disclosed in connection with process P1.

It is also advantageous to choose the appropriate catalyst and/or ligand from commercial catalogues such as “Metal Catalysts for Organic Synthesis” by Strem Chemicals or from reviews (Chemical Society Reviews (2014), 43, 3525, Coordination Chemistry Reviews (2004), 248, 2337 and references therein).

Suitable bases for carrying out process P3 can be as discosled in connection with process P1. Suitable solvents for carrying out process P3 can be as disclosed in connection with process P1.

Process P3 may be performed in an inert atmosphere. When carrying out process P3, 1 mole or an excess of compound of formula (IX) and from 1 to 5 moles of base and from 0.01 to 20 mole percent of a transition metal complex can be employed per mole of compound of formula (VIII). It is also possible to employ the reaction components in other ratios. Work-up is carried out by known methods.

Compounds of formula (I) wherein Q1represent C can be prepared by a process P4 which comprises the step of reacting a compound of formula (X) or one of its salts with a compound of formula (XI) as illustrated by the following reaction scheme:

wherein L represents CR4R5;R4and R5independently represent a hydrogen atom or a C1-C8alkyl;U4represents a bromine atom, a chlorine atom, an iodine atom, a mesyl group, a tosyl group or a triflyl group;W1represents a boron derivative such as a boronic acid, a boronic ester or a potassium trifluoroborate derivative;R1and R2independently represent a C1-C8-alkyl, a C2-C8-alkenyl, a C3-C7-cycloalkyl, an aryl or a heterocyclyl;R3represents a hydrogen atom; a C1-C8-alkyl; a C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; a C2-C8-alkenyl; a C2-C8-alkynyl; a C3-C7-cycloalkyl; a C4-C7-cycloalkenyl; an aryl; an aryl-C1-C8-alkyl; a heterocyclyl; a heterocyclyl-C1-C8-alkyl; a hydroxy-C1-C8-alkyl; a C1-C8-alkoxy-C1-C8-alkyl; a C1-C8-alkylcarbonyloxy-C1-C8-alkyl; an aryloxy-C1-C8-alkyl; a heterocyclyloxy-C1-C8-alkyl; an amino-C1-C8-alkyl; a C1-C8-alkylamino-C1-C8-alkyl; a di-C1-C8-alkylamino-C1-C8-alkyl; an arylamino-C1-C8-alkyl; a di-arylamino-C1-C8-alkyl; a heterocyclylamino-C1-C8-alkyl; a C1-C8-alkylcarbonylamino-C1-C8-alkyl; a C1-C8-alkoxycarbonylamino-C1-C8-alkyl; a C1-C8-alkylsulfanyl-C1-C8-alkyl; a C1-C8-alkylsulfinyl-C1-C8-alkyl; a C1-C8-alkylsulfonyl-C1-C8-alkyl or a cyano-C1-C8-alkyl; andA, B, n, p, X, Y and Z are as herein-defined.

It is to be understood that any of said R1, R2and R3may be substituted as disclosed in connection with R1, R2and R3of compounds of formula (I).

Compounds of formula (XI) can be prepared by known processes (Journal of the American Chemical Society (1957), 79, 6540; Journal of Organic Chemistry (2000), (65), 4913; Tetrahedron Letters (2002), 43, 8569).

Process P4 can be performed in the presence of a transition metal catalyst such as palladium and if appropriate in the presence of a phosphine ligand or a N-heterocyclic carbene ligand and if appropriate in the presence of a base and if appropriate in the presence of a solvent. Suitable palladium salts or complexes for this purpose can be as disclosed in connection with process P1.

Suitable bases for carrying out process P4 can be as disclosed in connection with process P1.

Suitable solvents for carrying out process P4 can be as disclosed in connection with process P1.

It can also be advantageous to carry out process P4 according to the invention, with a co-solvent such as water or an alcohol such as methanol, ethanol, propanol, isopropanol or tert-butanol.

Process P4 may be performed in an inert atmosphere. When carrying out process P4, 1 mole or an excess of compound of formula (XI) and from 1 to 5 moles of base and from 0.01 to 20 mole percent of a transition metal complex can be employed per mole of compound of formula (X). It is also possible to employ the reaction components in other ratios. Work-up is carried out by known methods.

Compounds of formula (I) wherein Q1represent C can be prepared by a process P5 which comprises the step of reacting a compound of formula (VIII) or one of its salts with a compound of formula (XII) as illustrated by the following reaction scheme:

wherein L represents CR4R5;R4and R5independently represent a hydrogen atom, a C1-C8-alkoxy or a C1-C8alkyl;U3represents a bromine atom, a chlorine atom, an iodine atom, a mesyl group, a tosyl group or a triflyl group;W2represents a boron derivative such as a boronic acid, a boronic ester or a potassium trifluoroborate derivative;R1and R2independently represent a C1-C8-alkyl, a C2-C8-alkenyl, a C3-C7-cycloalkyl, an aryl or a heterocyclyl;R3represents a hydrogen atom; a C1-C8-alkyl; a C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; a C2-C8-alkenyl; a C2-C8-alkynyl; a C3-C7-cycloalkyl; a C4-C7-cycloalkenyl; an aryl; an aryl-C1-C8-alkyl; a heterocyclyl; a heterocyclyl-C1-C8-alkyl; a hydroxy-C1-C8-alkyl; a C1-C8-alkoxy-C1-C8-alkyl; a C1-C8-alkylcarbonyloxy-C1-C8-alkyl; an aryloxy-C1-C8-alkyl; a heterocyclyloxy-C1-C8-alkyl; an amino-C1-C8-alkyl; a C1-C8-alkylamino-C1-C8-alkyl; a di-C1-C8-alkylamino-C1-C8-alkyl; an arylamino-C1-C8-alkyl; a di-arylamino-C1-C8-alkyl; a heterocyclylamino-C1-C8-alkyl; a C1-C8-alkylcarbonylamino-C1-C8-alkyl; a C1-C8-alkoxycarbonylamino-C1-C8-alkyl; a C1-C8-alkylsulfanyl-C1-C8-alkyl; a C1-C8-alkylsulfinyl-C1-C8-alkyl; a C1-C8-alkylsulfonyl-C1-C8-alkyl or a cyano-C1-C8-alkyl; andA, B, n, p, X, Y and Z are as herein-defined.

It is to be understood that any of said R1, R2and R3may be substituted as disclosed in connection with R1, R2and R3of compounds of formula (I).

Compounds of formula (XII) can be prepared from compounds of formula (XI) by known processes (Tetrahedron Letters (2003), 44, 233 and Chemistry Letters (2002), 780).

Process P5 can be performed in the presence of a transition metal catalyst such as palladium and if appropriate in the presence of a phosphine ligand or a N-heterocyclic carbene ligand and if appropriate in the presence of a base and if appropriate in the presence of a solvent. Suitable palladium salts or complexes for this purpose can be as disclosed in connection with process P1.

Suitable bases for carrying out process P5 can be as disclosed in connection with process P1.

Suitable solvents for carrying out process P5 can be as disclosed in connection with process P1.

It can also be advantageous to carry out process P5 according to the invention, with a co-solvent such as water or an alcohol such as methanol, ethanol, propanol, isopropanol or tert-butanol.

Process P5 may be performed in an inert atmosphere. When carrying out process P5, 1 mole or an excess of compound of formula (XII) and from 1 to 5 moles of base and from 0.01 to 20 mole percent of a transition metal complex can be employed per mole of compound of formula (VIII). It is also possible to employ the reaction components in other ratios. Work-up is carried out by known methods.

Compounds of formula (I) wherein Q1represent N can be prepared by a process P6 which comprises the step of reacting a compound of formula (XIII) or one of its salts with a compound of formula (XI) as illustrated by the following reaction scheme:

wherein L represents CR4R5;R4and R5independently represent a hydrogen atom or a C1-C8alkyl;U4represents a bromine atom, a chlorine atom, an iodine atom, a mesyl group, a tosyl group or a triflyl group;R1and R2independently represent a C1-C8-alkyl, a C2-C8-alkenyl, a C3-C7-cycloalkyl, an aryl or a heterocyclyl;R3represents a hydrogen atom; a C1-C8-alkyl; a C1-C8-halogenoalkyl comprising up to 9 halogen atoms that can be the same or different; a C2-C8-alkenyl; a C2-C8-alkynyl; a C3-C7-cycloalkyl; a C4-C7-cycloalkenyl; an aryl; an aryl-C1-C8-alkyl; a heterocyclyl; a heterocyclyl-C1-C8-alkyl; a hydroxy-C1-C8-alkyl; a C1-C8-alkoxy-C1-C8-alkyl; a C1-C8-alkylcarbonyloxy-C1-C8-alkyl; an aryloxy-C1-C8-alkyl; a heterocyclyloxy-C1-C8-alkyl; an amino-C1-C8-alkyl; a C1-C8-alkylamino-C1-C8-alkyl; a di-C1-C8-alkylamino-C1-C8-alkyl; an arylamino-C1-C8-alkyl; a di-arylamino-C1-C8-alkyl; a heterocyclylamino-C1-C8-alkyl; a C1-C8-alkylcarbonylamino-C1-C8-alkyl; a C1-C8-alkoxycarbonylamino-C1-C8-alkyl; a C1-C8-alkylsulfanyl-C1-C8-alkyl; a C1-C8-alkylsulfinyl-C1-C8-alkyl; a C1-C8-alkylsulfonyl-C1-C8-alkyl or a cyano-C1-C8-alkyl; andA, B, n, p, X, Y and Z are as herein-defined.

It is to be understood that any of said R1, R2and R3may be substituted as disclosed in connection with R1, R2and R3of compounds of formula (I).

Compounds of formula (XI) can be prepared by known processes (Journal of the American Chemical Society (1957), 79, 6540; Journal of Organic Chemistry (2000), (65), 4913; Tetrahedron Letters (2002), 43, 8569).

Compounds of formula (XIII) or their tautomers, are commercially available or can be prepared by well known processes.

Process P6 can be performed, if appropriate, in the presence of a suitable base and if appropriate in the presence of a solvent.

Suitable bases for carrying out process P6 can be as disclosed in connection with process P1.

Suitable solvents for carrying out process P6 can be as disclosed in connection with process P1.

Process P6 may be performed in an inert atmosphere. When carrying out process P6, 1 mole or an excess of compound of formula (XI) and from 1 to 5 moles of base can be employed per mole of compound of formula (XIII). It is also possible to employ the reaction components in other ratios. Work-up is carried out by known methods.

Processes P1, P2, P3, P4, P5 and P6 are generally carried out under atmospheric pressure. It is also possible to operate under elevated or reduced pressure.

When carrying out processes P1, P2, P3, P4, P5 and P6, the reaction temperatures can be varied within a relatively wide range. In general, these processes are carried out at temperatures from −78° C. to 200° C., preferably from −78° C. to 150° C. A way to control the temperature for the processes is to use microwave technology.

In general, the reaction mixture is concentrated under reduced pressure. The residue that remains can be freed by known methods, such as chromatography or crystallization, from any impurities that can still be present.

Work-up is carried out by customary methods. Generally, the reaction mixture is treated with water and the organic phase is separated off and, after drying, concentrated under reduced pressure. If appropriate, the remaining residue can, be freed by customary methods, such as chromatography, crystallization or distillation, from any impurities that may still be present.

The compounds of formula (I) can be prepared according to the general processes of preparation described above. It will nevertheless be understood that, on the basis of his general knowledge and of available publications, the skilled worker will be able to adapt the methods according to the specifics of each compound, which it is desired to synthesize.

Intermediates for the Preparation of the Active Ingredients

The present invention also relates to intermediates for the preparation of compounds of formula (I). Thus, the present invention relates to compounds of formula (IIa) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom, provided that the compound of formula (IIa) does not represent:(2-chloropyridin-3-yl)(8-chloroquinolin-3-yl)methanone [1501960-80-0],(2-chloropyridin-3-yl)(8-fluoroquinolin-3-yl)methanone [1501960-57-1],(2-chloropyridin-3-yl)(quinolin-3-yl)methanone [1326548-06-4] andN-(2-chloropyridin-3-yl)quinoxalin-2-amine [1245798-46-2].

The following compounds of formula (IIa) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:2-[(2-bromopyridin-3-yl)oxy]-3-chloroquinoxaline [1065484-71-0].

Preferred compounds of formula (IIa) according to the invention are:2-[(2-bromopyridin-3-yl)oxy]-5,6-difluoro-3-methylquinoxaline,2-[(2-bromo-5-chloropyridin-3-yl)oxy]-5,6-difluoro-3-methylquinoxaline,2-[(2-bromopyridin-3-yl)oxy]-5,6-difluoroquinoxaline andN-(2-chloropyridin-3-yl)-8-fluoroquinolin-3-amine.

The present invention also relates to compounds of formula (lib) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

The following compounds of formula (lib) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:3-[(3-bromopyridin-4-yl)oxy]quinoline [1990739-14-4],(3-chloropyridin-4-yl)(quinolin-3-yl)methanone [1983655-31-7],(3-chloropyridin-4-yl)(quinolin-3-yl)methanol [1980501-48-1],5-bromo-4-(quinolin-3-yloxy)pyridin-3-amine [1927506-36-2],N-(3-bromopyridin-4-yl)quinolin-3-amine [1923361-93-6],3-[(3-bromopyridin-4-yl)oxy]quinoline-4-carboxylic acid [1921389-65-2] and3-[(3-chloropyridin-4-yl)oxy]quinoline-4-carboxylic acid [1542049-36-4].

Preferred compounds of formula (lib) according to the invention are:3-[(3-bromo-2-fluoropyridin-4-yl)oxy]quinoline,2-[(5-bromo-2-chloropyridin-4-yl)oxy]-5,6-difluoro-3-methylquinoxaline,2-[(3-bromopyridin-4-yl)oxy]-5,6-difluoroquinoxaline,N-(3-bromo-2-chloropyridin-4-yl)quinolin-3-amine,3-[(3-bromo-2-methoxypyridin-4-yl)oxy]-7,8-difluoro-2-methylquinoline,3-[(3-bromo-2-fluoropyridin-4-yl)oxy]-8-fluoroquinoline,3-[(3-bromo-2-chloropyridin-4-yl)oxy]quinoline,N-(3-bromo-2-fluoropyridin-4-yl)quinolin-3-amine,3-{[3-bromo-2-(trifluoromethyl)pyridin-4-yl]oxy}-7,8-difluoro-2-methylquinoline andN-[3-bromo-2-(trifluoromethyl)pyridin-4-yl]-7,8-difluoro-2-methylquinolin-3-amine.

The present invention also relates to compounds of formula (IIc) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

Preferred compounds of formula (IIc) according to the invention are:2-[(4-bromo-5-chloropyridin-3-yl)oxy]-5,6-difluoro-3-methylquinoxaline,3-[(4-bromopyridin-3-yl)oxy]-2-methylquinoline and2-[(4-bromopyridin-3-yl)oxy]-5,6-difluoro-3-methylquinoxaline.

The present invention also relates to compounds of formula (IId) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom, provided that the compound of formula (IId) does not represent:2-[(3-chloro-5-nitropyridin-2-yl)oxy]quinoxaline [1389318-96-0],N-(3,5-dichloro-4-methylpyridin-2-yl)quinoxalin-2-amine [1258454-20-4],N-(3-bromopyridin-2-yl)quinoxalin-2-amine [1245798-50-8],N-(3-bromopyridin-2-yl)quinolin-3-amine [1193779-14-4],3-[(3-chloro-5-nitropyridin-2-yl)oxy]quinoline [1013695-65-2] and6,7-dichloro-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]sulfanyl}-3-isopropylquinoxaline [281209-22-1].

Preferred compounds of formula (IId) according to the invention are:2-[(3-bromo-5-chloropyridin-2-yl)oxy]-5,6-difluoro-3-methylquinoxaline andN-(3-bromo-5-chloropyridin-2-yl)-7,8-difluoro-2-methylquinolin-3-amine.

The present invention also relates to compounds of formula (lile) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom, provided that the compound of formula (lile) does not represent:N-(2,5-dichloropyrimidin-4-yl)quinolin-3-amine [1803564-37-5] and3-[(5-bromo-2-chloro-6-methylpyrimidin-4-yl)sulfanyl]quinoxalin-2-amine [1781256-09-4].

The following compounds of formula (lile) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:3-[(5-chloropyrimidin-4-yl)oxy]quinoline-4-carboxylic acid [1981383-33-8],3-[(5-bromopyrimidin-4-yl)oxy]quinoline [1967865-19-5],5-bromo-6-(quinolin-3-yloxy)pyrimidin-4(1H)-one [1965174-05-3],3-[(2,5-dichloropyrimidin-4-yl)oxy]quinoline [1962434-15-6],3-[(5-bromo-6-chloropyrimidin-4-yl)oxy]quinoline [1959489-27-0],5-iodo-6-(quinolin-3-yloxy)pyrimidin-4(1H)-one [1927140-49-5],5-chloro-6-(quinolin-3-yloxy)pyrimidin-4(1H)-one [1926941-07-2],3-[(5-bromo-2-chloropyrimidin-4-yl)oxy]quinoline [1925623-65-9],3-[(5-iodopyrimidin-4-yl)oxy]quinoline [1925480-63-2],5-iodo-6-(quinolin-3-ylamino)pyrimidin-4(1H)-one [1777748-34-1],5-bromo-6-(quinolin-3-ylamino)pyrimidin-4(1H)-one [1715463-63-0],5-chloro-6-(quinolin-3-ylamino)pyrimidin-4(1H)-one [1712030-77-7],3-[(5-iodopyrimidin-4-yl)oxy]quinoline-4-carboxylic acid [1536636-01-7],3-[(5-bromopyrimidin-4-yl)oxy]quinoline-4-carboxylic acid [1520429-21-3],N-(5-bromopyrimidin-4-yl)quinolin-3-amine [1508375-21-0] andN-(5-iodopyrimidin-4-yl)quinolin-3-amine [1500864-31-2].

Preferred compound of formula (lile) according to the invention is 3-[(5-bromo-6-chloropyrimidin-4-yl)oxy]quinoline.

The present invention also relates to compounds of formula (IIf) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C, Q2represents O, S or NR7, R7represents a hydrogen atom or a C1-C6-alkyl group, and U1arepresents a chlorine atom, a bromine atom or an iodine atom, provided that the compound of formula (IIf) does not represent:(3-bromo-2-furyl)[4-phenyl-8-(trifluoromethyl)quinolin-3-yl]methanone [854769-03-2].

The following compounds of formula (IIf) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:(3-bromo-2-furyl)(quinolin-3-yl)methanone [1992981-63-1],(3-bromo-2-furyl)(quinolin-3-yl)methanol [1988561-37-0],(3-bromo-2-thienyl)(quinoxalin-2-yl)methanone [1988274-50-5],(3-bromo-2-thienyl)(quinoxalin-2-yl)methanol [1986915-41-6],(3-chloro-2-thienyl)(quinoxalin-2-yl)methanone [1984509-02-5],(3-chloro-4-methyl-2-thienyl)(quinolin-3-yl)methanol [1969501-74-3],(3-chloro-4-methyl-2-thienyl)(quinolin-3-yl)methanone [1969098-55-2],(3-chloro-2-thienyl)(quinoxalin-2-yl)methanol [1962273-54-6],(3-bromo-2-furyl)(quinoxalin-2-yl)methanone [1961390-50-0],(3-bromo-2-furyl)(quinoxalin-2-yl)methanol [1933405-58-3],(3-bromo-2-thienyl)(quinolin-3-yl)methanone [1778818-45-3],(3-chloro-2-thienyl)(quinolin-3-yl)methanone [1771253-19-0],(3-chloro-2-thienyl)(quinolin-3-yl)methanol [1711813-11-4] and(3-bromo-2-thienyl)(quinolin-3-yl)methanol [1545104-42-4].

Preferred compound of formula (IIf) according to the invention is 3-[(3-bromo-2-thienyl)oxy]-7,8-difluoro-2-methylquinoline.

The present invention also relates to compounds of formula (IIg) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C, Q2represents O, S or NR7, R7represents a hydrogen atom or a C1-C6-alkyl group, and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

The following compounds of formula (IIg) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:(4-bromo-3-thienyl)(quinoxalin-2-yl)methanol [1988275-71-3] and(4-bromo-3-thienyl)(quinoxalin-2-yl)methanone [1925385-95-0].

The present invention also relates to compounds of formula (IIh) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C, Q2represents O, S or NR7, R7represents a hydrogen atom or a C1-C6-alkyl group, and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

The following compounds of formula (IIh) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:(2-bromo-3-furyl)(quinolin-3-yl)methanol [1988401-43-9],(2,5-dibromo-3-thienyl)(quinolin-3-yl)methanone [1986665-71-7],(2-chloro-3-furyl)(quinolin-3-yl)methanone [1985676-26-3],(2-chloro-3-furyl)(quinolin-3-yl)methanol [1970325-78-0],(2-bromo-3-furyl)(quinolin-3-yl)methanone [1968170-83-3],(2,5-dibromo-3-thienyl)(quinolin-3-yl)methanol [1962033-74-4],(2,5-dichloro-3-thienyl)(quinolin-3-yl)methanone [1931539-75-1] and(2,5-dichloro-3-thienyl)(quinolin-3-yl)methanol [1927337-73-2].

The present invention also relates to compounds of formula (VIIa) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U5represents a chlorine atom or a fluorine atom.

The following compounds of formula (VIIa) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:3-[(2-chloropyridin-4-yl)oxy]quinoline [1929233-74-8],3-[(2-fluoropyridin-4-yl)oxy]quinoline [1929005-49-1],3-[(2-chloro-5-methylpyridin-4-yl)oxy]quinoline [1927074-40-5],(2-chloropyridin-4-yl)(quinolin-3-yl)methanone [1527953-24-7] and(2-chloropyridin-4-yl)(quinolin-3-yl)methanol [1511654-56-0].

Preferred compounds of formula (VIIa) according to the invention are:3-[(2-chloropyridin-4-yl)oxy]quinoline,3-[(2-fluoropyridin-4-yl)oxy]-2-methylquinoline and3-[(2-fluoropyridin-4-yl)oxy]quinoline.

The present invention also relates to compounds of formula (VIIb) as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U5represents a chlorine atom or a fluorine atom, provided that the compound of formula (VIIb) does not represent:2-[(6-chloropyrimidin-4-yl)oxy]quinoxaline [1065484-81-2].

The following compounds of formula (VIIb) are mentioned in chemical databases and/or suppliers' databases but without any references or information which enable these to be prepared and separated:3-[(6-chloro-2-methylpyrimidin-4-yl)oxy]quinoline [1984241-25-9],3-[(6-chloro-2-cyclopropylpyrimidin-4-yl)oxy]quinoline [1967865-14-0],3-{[6-chloro-2-(methoxymethyl)pyrimidin-4-yl]oxy}quinoline [1929007-59-9],3-[(6-fluoropyrimidin-4-yl)oxy]quinoline [1928990-99-1],3-[(6-chloro-2-isopropylpyrimidin-4-yl)oxy]quinoline [1928619-40-2],3-[(6-chloro-2-ethylpyrimidin-4-yl)oxy]quinoline [1927140-08-6],3-[(6-chloropyrimidin-4-yl)oxy]quinoline [1927140-07-5] and3-[(6-chloro-2-propylpyrimidin-4-yl)oxy]quinoline [1926935-32-1].

Preferred compound of formula (VIIb) according to the invention is 3-[(6-fluoropyrimidin-4-yl)oxy]quinoline.

Compositions and Formulations

The present invention further relates to a composition, in particular a composition for controlling unwanted microorganisms. The compositions may be applied to the microorganisms and/or in their habitat.

The composition typically comprises one or more compounds of formula (I) and at least one agriculturally suitable auxiliary, e.g. carrier(s) and/or surfactant(s).

A carrier is a solid or liquid, natural or synthetic, organic or inorganic substance that is generally inert. The carrier generally improves the application of the compounds, for instance, to plants, plants parts or seeds.

Examples of suitable solid carriers include, but are not limited to, ammonium salts, natural rock flours, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth, and synthetic rock flours, such as finely divided silica, alumina and silicates. Examples of typically useful solid carriers for preparing granules include, but are not limited to crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, synthetic granules of inorganic and organic flours and granules of organic material such as paper, sawdust, coconut shells, maize cobs and tobacco stalks. Examples of suitable liquid carriers include, but are not limited to, water, organic solvents and combinations thereof. Examples of suitable solvents include polar and nonpolar organic chemical liquids, for example from the classes of aromatic and nonaromatic hydrocarbons (such as cyclohexane, paraffins, alkylbenzenes, xylene, toluene alkylnaphthalenes, chlorinated aromatics or chlorinated aliphatic hydrocarbons such as chlorobenzenes, chloroethylenes or methylene chloride), alcohols and polyols (which may optionally also be substituted, etherified and/or esterified, such as butanol or glycol), ketones (such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone), esters (including fats and oils) and (poly)ethers, unsubstituted and substituted amines, amides (such as dimethylformamide), lactams (such as N-alkylpyrrolidones) and lactones, sulfones and sulfoxides (such as dimethyl sulfoxide). The carrier may also be a liquefied gaseous extender, i.e. liquid which is gaseous at standard temperature and under standard pressure, for example aerosol propellants such as halohydrocarbons, butane, propane, nitrogen and carbon dioxide. The amount of carrier typically ranges from 1 to 99.99%, preferably from 5 to 99.9%, more preferably from 10 to 99.5%, and most preferably from 20 to 99% by weight of the composition.

The surfactant can be an ionic (cationic or anionic) or non-ionic surfactant, such as ionic or non-ionic emulsifier(s), foam former(s), dispersant(s), wetting agent(s) and any mixtures thereof. Examples of suitable surfactants include, but are not limited to, salts of polyacrylic acid, salts of lignosulfonic acid, salts of phenolsulfonic acid or naphthalenesulfonic acid, polycondensates of ethylene and/or propylene oxide with fatty alcohols, fatty acids or fatty amines (polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers), substituted phenols (preferably alkylphenols or arylphenols), salts of sulfosuccinic esters, taurine derivatives (preferably alkyl taurates), phosphoric esters of polyethoxylated alcohols or phenols, fatty esters of polyols and derivatives of compounds containing sulfates, sulfonates, phosphates (for example, alkylsulfonates, alkyl sulfates, arylsulfonates) and protein hydrolysates, lignosulfite waste liquors and methylcellulose. A surfactant is typically used when the compound(s) of formula (I) and/or the carrier is insoluble in water and the application is made with water. Then, the amount of surfactants typically ranges from 5 to 40% by weight of the composition.

Further examples of suitable auxiliaries include water repellents, siccatives, binders (adhesive, tackifier, fixing agent, such as carboxymethylcellulose, natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, natural phospholipids such as cephalins and lecithins and synthetic phospholipids, polyvinylpyrrolidone and tylose), thickeners, stabilizers (e.g. cold stabilizers, preservatives, antioxidants, light stabilizers, or other agents which improve chemical and/or physical stability), dyes or pigments (such as inorganic pigments, e.g. iron oxide, titanium oxide and Prussian Blue; organic dyes, e.g. alizarin, azo and metal phthalocyanine dyes), antifoams (e.g. silicone antifoams and magnesium stearate), preservatives (e.g. dichlorophene and benzyl alcohol hemiformal), secondary thickeners (cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and finely divided silica), stickers, gibberellins and processing auxiliaries, mineral and vegetable oils, perfumes, waxes, nutrients (including trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc), protective colloids, thixotropic substances, penetrants, sequestering agents and complex formers.

The choice of the auxiliaries is related to the intended mode of application of the compound(s) of the invention and/or to its physical properties. Furthermore, the auxiliaries may be chosen to impart particular properties (technical, physical and/or biological properties) to the compositions or use forms prepared therefrom. The choice of auxiliaries may allow customizing the compositions to specific needs.

The composition may be in any customary form, such as solutions (e.g aqueous solutions), emulsions, wettable powders, water- and oil-based suspensions, powders, dusts, pastes, soluble powders, soluble granules, granules for broadcasting, suspoemulsion concentrates, natural or synthetic products impregnated with one or more compounds of formula (I), fertilizers and also microencapsulations in polymeric substances. The compound(s) of formula (I) may be present in a suspended, emulsified or dissolved form.

The composition may be provided to the end user as ready-for-use formulation, i.e. the compositions may be directly applied to the plants or seeds by a suitable device, such as a spraying or dusting device. Alternatively, the compositions may be provided to the end user in the form of concentrates which have to be diluted, preferably with water, prior to use.

The composition can be prepared in conventional manners, for example by mixing the compound(s) of formula (I) with one or more suitable auxiliaries, such as disclosed herein above.

The composition contains generally from 0.01 to 99% by weight, from 0.05 to 98% by weight, preferably from 0.1 to 95% by weight, more preferably from 0.5 to 90% by weight, most preferably from 1 to 80% by weight of the compound of formula (I). It is possible that a composition comprises two or more compounds of formula (I). In such case the outlined ranges refer to the total amount of compounds of formula (I).

The compound(s) of formula (I) and compositions comprising thereof can be mixed with other active ingredients like fungicides, bactericides, acaricides, nematicides, insecticides, herbicides, fertilizers, growth regulators, safeners or semiochemicals. This may allow to broaden the activity spectrum or to prevent development of resistance. Examples of known fungicides, insecticides, acaricides, nematicides and bactericides are disclosed in the Pesticide Manual, 17th Edition.

Examples of especially preferred fungicides which could be mixed with the compounds of formula (I) are:

8) Inhibitors of the ATP production, for example (8.001) silthiofam.

14) Compounds capable to act as an uncoupler, for example (14.001) fluazinam, (14.002) meptyldinocap.

All named mixing partners of the classes (1) to (15) as described here above can be present in the form of the free compound and/or, if their functional groups enable this, an agriculturally acceptable salt thereof.

The compounds of formula (I) and compositions comprising thereof may also be combined with one or more biological control agents.

Examples of biological control agents which may be combined with the compound of formula (I) and composition comprising thereof are:

(A) Antibacterial agents selected from the group of:

(A2) fungi, such as (A2.1)Aureobasidium pullulans, in particular blastospores of strain DSM14940; (A2.2)Aureobasidium pullulansblastospores of strain DSM 14941; (A2.3)Aureobasidium pullulans, in particular mixtures of blastospores of strains DSM14940 and DSM14941;

(B) Fungicides selected from the group of:

Further examples of biological control agents which may be combined with the compounds of formula (I) and compositions comprising thereof are:

bacteria and fungi which can be added as ‘inoculant’ to plants or plant parts or plant organs and which, by virtue of their particular properties, promote plant growth and plant health. Examples are:Agrobacteriumspp.,Azorhizobium caulinodans, Azospirillumspp.,Azotobacterspp.,Bradyrhizobiumspp.,Burkholderiaspp., in particularBurkholderia cepacia(formerly known asPseudomonas cepacia),Gigasporaspp., orGigaspora monosporum, Glomusspp.,Laccariaspp.,Lactobacillus buchneri, Paraglomusspp.,Pisolithus tinctorus, Pseudomonasspp.,Rhizobiumspp., in particularRhizobium trifolii, Rhizopogonspp.,Sclerodermaspp.,Suillusspp., andStreptomycesspp.

Examples of insecticides, acaricides and nematicides, respectively, which could be mixed with the compounds of formula (I) and compositions comprising thereof are:

(2) GABA-gated chloride channel blockers, such as, for example, cyclodiene-organochlorines, for example chlordane and endosulfan or phenylpyrazoles (fiproles), for example ethiprole and fipronil.

(12) Inhibitors of mitochondrial ATP synthase, such as, ATP disruptors such as, for example, diafenthiuron or organotin compounds, for example azocyclotin, cyhexatin and fenbutatin oxide or propargite or tetradifon.

(13) Uncouplers of oxidative phosphorylation via disruption of the proton gradient, such as, for example, chlorfenapyr, DNOC and sulfluramid.

(16) Inhibitors of chitin biosynthesis, type 1, for example buprofezin.

(20) Mitochondrial complex III electron transport inhibitors, such as, for example, hydramethylnone or acequinocyl or fluacrypyrim.

(21) Mitochondrial complex I electron transport inhibitors, such as, for example from the group of the METI acaricides, e.g. fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad and tolfenpyrad or rotenone (Derris).

Examples of herbicides which could be mixed with with the compounds of formula (I) and compositions comprsing thereof are:

Examples for plant growth regulators are:

Methods and Uses

The compounds of formula (I) and compositions comprising thereof have potent microbicidal activity and/or plant defense modulating potential. They can be used for controlling unwanted microorganisms, such as unwanted fungi and bacteria. They can be particularly useful in crop protection (they control microorganisms that cause plants diseases) or for protecting materials (e.g. industrial materials, timber, storage goods) as described in more details herein below. More specifically, the compounds of formula (I) and compositions comprising thereof can be used to protect seeds, germinating seeds, emerged seedlings, plants, plant parts, fruits, harvest goods and/or the soil in which the plants grow from unwanted microorganisms.

Control or controlling as used herein encompasses protective, curative and eradicative treatment of unwanted microorganisms. Unwanted microorganisms may be pathogenic bacteria, pathogenic virus, pathogenic oomycetes or pathogenic fungi, more specifically phytopathogenic bacteria, phytopathogenic virus, phytopathogenic oomycetes or phytopathogenic fungi. As detailed herein below, these phytopathogenic microorganims are the causal agents of a broad spectrum of plants diseases.

More specifically, the compounds of formula (I) and compositions comprising thereof can be used as fungicides. For the purpose of the specification, the term “fungicide” refers to a compound or composition that can be used in crop protection for the control of unwanted fungi, such as Plasmodiophoromycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes and/or for the control of Oomycetes.

The compounds of formula (I) and compositions comprising thereof may also be used as antibacterial agent. In particular, they may be used in crop protection, for example for the control of unwanted bacteria, such as Pseudomonadaceae, Rhizobiaceae, Xanthomonadaceae, Enterobacteriaceae, Corynebacteriaceae and Streptomycetaceae.

The compounds of formula (I) and compositions comprising thereof may also be used as antiviral agent in crop protection. For example the compounds of formula (I) and compositions comprising thereof may have effects on diseases from plant viruses, such as the tobacco mosaic virus (TMV), tobacco rattle virus, tobacco stunt virus (TStuV), tobacco leaf curl virus (VLCV), tobacco nervilia mosaic virus (TVBMV), tobacco necrotic dwarf virus (TNDV), tobacco streak virus (TSV), potato virus X (PVX), potato viruses Y, S, M, and A, potato acuba mosaic virus (PAMV), potato mop-top virus (PMTV), potato leaf-roll virus (PLRV), alfalfa mosaic virus (AMV), cucumber mosaic virus (CMV), cucumber green mottlemosaic virus (CGMMV), cucumber yellows virus (CuYV), watermelon mosaic virus (WMV), tomato spotted wilt virus (TSWV), tomato ringspot virus (TomRSV), sugarcane mosaic virus (SCMV), rice drawf virus, rice stripe virus, rice black-streaked drawf virus, strawberry mottle virus (SMoV), strawberry vein banding virus (SVBV), strawberry mild yellow edge virus (SMYEV), strawberry crinkle virus (SCrV), broad beanwilt virus (BBWV), and melon necrotic spot virus (MNSV).

The present invention also relates to a method for controlling unwanted microorganisms, in particular unwanted phytopathogenic microorganisms such as unwanted fungi, oomycetes and bacteria, comprising the step of applying one or more compounds of formula (I) or a composition comprising thereof to the microorganisms and/or their habitat (to the plants, plant parts, seeds, fruits or to the soil in which the plants grow).

Typically, when the compounds of formula (I) and compositions comprising thereof are used in curative or protective methods for controlling phytopathogenic fungi and/or phytopathogenic oomycetes, an effective and plant-compatible amount thereof is applied to the plants, plant parts, fruits, seeds or to the soil or substrates in which the plants grow. Suitable substrates that may be used for cultivating plants include inorganic based substrates, such as mineral wool, in particular stone wool, perlite, sand or gravel; organic substrates, such as peat, pine bark or sawdust; and petroleum based substrates such as polymeric foams or plastic beads. Effective and plant-compatible amount means an amount that is sufficient to control or destroy the fungi present or liable to appear on the cropland and that does not entail any appreciable symptom of phytotoxicity for said crops. Such an amount can vary within a wide range depending on the fungus to be controlled, the type of crop, the crop growth stage, the climatic conditions and the respective compounds of formula (I) and compositions comprising thereof. This amount can be determined by systematic field trials that are within the capabilities of a person skilled in the art.

Plants and Plant Parts

The compounds of formula (I) and compositions comprising thereof may be applied to any plants or plant parts.

Plants mean all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants). Crop plants may be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the genetically modified plants (GMO or transgenic plants) and the plant cultivars which are protectable and non-protectable by plant breeders' rights.

Genetically modified plants (GMO or transgenic plants) are plants in which a heterologous gene has been stably integrated into the genome. The expression “heterologous gene” essentially means a gene which is provided or assembled outside the plant and when introduced in the nuclear, chloroplastic or mitochondrial genome. This gene gives the transformed plant new or improved agronomic or other properties by expressing a protein or polypeptide of interest or by downregulating or silencing other gene(s) which are present in the plant (using for example, antisense technology, cosuppression technology, RNA interference—RNAi-technology or microRNA—miRNA—technology). A heterologous gene that is located in the genome is also called a transgene. A transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.

Plant cultivars are understood to mean plants which have new properties (“traits”) and have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be cultivars, varieties, bio- or genotypes.

Plant parts are understood to mean all parts and organs of plants above and below the ground, such as shoots, leaves, needles, stalks, stems, flowers, fruit bodies, fruits, seeds, roots, tubers and rhizomes. The plant parts also include harvested material and vegetative and generative propagation material, for example cuttings, tubers, rhizomes, slips and seeds.

Plants which may be treated in accordance with the methods of the invention include the following: cotton, flax, grapevine, fruit, vegetables, such as Rosaceae sp. (for example pome fruits such as apples and pears, but also stone fruits such as apricots, cherries, almonds and peaches, and soft fruits such as strawberries),Ribesioidaesp.,Juglandaceaesp.,Betulaceaesp.,Anacardiaceaesp.,Fagaceaesp.,Moraceaesp.,Oleaceaesp.,Actinidaceaesp.,Lauraceaesp.,Musaceaesp. (for example banana trees and plantations),Rubiaceaesp. (for example coffee),Theaceaesp.,Sterculiceaesp.,Rutaceaesp. (for example lemons, oranges and grapefruit);Solanaceaesp. (for example tomatoes),Liliaceaesp.,Asteraceaesp. (for example lettuce),Umbelliferaesp.,Cruciferaesp.,Chenopodiaceaesp.,Cucurbitaceaesp. (for example cucumber),Alliaceaesp. (for example leek, onion),Papilionaceaesp. (for example peas); major crop plants, such asGramineaesp. (for example maize, turf, cereals such as wheat, rye, rice, barley, oats, millet and triticale),Asteraceaesp. (for example sunflower),Brassicaceaesp. (for example white cabbage, red cabbage, broccoli, cauliflower, Brussels sprouts, pak choi, kohlrabi, radishes, and oilseed rape, mustard, horseradish and cress),Fabacaesp. (for example bean, peanuts),Papilionaceaesp. (for example soya bean),Solanaceaesp. (for example potatoes),Chenopodiaceaesp. (for example sugar beet, fodder beet, swiss chard, beetroot); useful plants and ornamental plants for gardens and wooded areas; and genetically modified varieties of each of these plants.

Plants and plant cultivars which may be treated by the above disclosed methods include plants and plant cultivars which are resistant against one or more biotic stresses, i.e. said plants show a better defense against animal and microbial pests, such as against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids.

Plants and plant cultivars which may be treated by the above disclosed methods include those plants which are resistant to one or more abiotic stresses. Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of nitrogen nutrients, limited availability of phosphorus nutrients, shade avoidance.

Plants and plant cultivars which may be treated by the above disclosed methods include those plants characterized by enhanced yield characteristics. Increased yield in said plants may be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation. Yield may furthermore be affected by improved plant architecture (under stress and non-stress conditions), including but not limited to, early flowering, flowering control for hybrid seed production, seedling vigor, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance. Further yield traits include seed composition, such as carbohydrate content and composition for example cotton or starch, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.

Plants and plant cultivars which may be treated by the above disclosed methods include plants and plant cultivars which are hybrid plants that already express the characteristic of heterosis or hybrid vigor which results in generally higher yield, vigor, health and resistance towards biotic and abiotic stresses.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars which are herbicide-tolerant plants, i.e. plants made tolerant to one or more given herbicides. Such plants can be obtained either by genetic transformation, or by selection of plants containing a mutation imparting such herbicide tolerance.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars which are insect-resistant transgenic plants, i.e. plants made resistant to attack by certain target insects. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars which are disease-resistant transgenic plants, i.e. plants made resistant to attack by certain target insects. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars which are tolerant to abiotic stresses. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such stress resistance.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars which show altered quantity, quality and/or storage-stability of the harvested product and/or altered properties of specific ingredients of the harvested product.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars, such as cotton plants, with altered fiber characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered fiber characteristics.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars, such as oilseed rape or relatedBrassicaplants, with altered oil profile characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered oil profile characteristics.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars, such as oilseed rape or relatedBrassicaplants, with altered seed shattering characteristics. Such plants can be obtained by genetic transformation, or by selection of plants contain a mutation imparting such altered seed shattering characteristics and include plants such as oilseed rape plants with delayed or reduced seed shattering.

Plants and plant cultivars (obtained by plant biotechnology methods such as genetic engineering) which may be treated by the above disclosed methods include plants and plant cultivars, such as Tobacco plants, with altered post-translational protein modification patterns.

Non-limiting examples of pathogens of fungal diseases which may be treated in accordance with the invention include:

diseases of soya beans:

Material Protection

The compounds of formula (I) and compositions comprising thereof may also be used in the protection of materials, especially for the protection of industrial materials against attack and destruction by phytopathogenic fungi.

In addition, the compounds of formula (I) and compositions comprising thereof may be used as antifouling compositions, alone or in combinations with other active ingredients.

Industrial materials in the present context are understood to mean inanimate materials which have been prepared for use in industry. For example, industrial materials which are to be protected from microbial alteration or destruction may be adhesives, glues, paper, wallpaper and board/cardboard, textiles, carpets, leather, wood, fibers and tissues, paints and plastic articles, cooling lubricants and other materials which can be infected with or destroyed by microorganisms. Parts of production plants and buildings, for example cooling-water circuits, cooling and heating systems and ventilation and air-conditioning units, which may be impaired by the proliferation of microorganisms may also be mentioned within the scope of the materials to be protected. Industrial materials within the scope of the present invention preferably include adhesives, sizes, paper and card, leather, wood, paints, cooling lubricants and heat transfer fluids, more preferably wood.

The compounds of formula (I) and compositions comprising thereof may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.

In the case of treatment of wood the compounds of formula (I) and compositions comprising thereof may also be used against fungal diseases liable to grow on or inside timber.

Timber means all types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high-density wood, laminated wood, and plywood. In addition, the compounds of formula (I) and compositions comprising thereof may be used to protect objects which come into contact with saltwater or brackish water, especially hulls, screens, nets, buildings, moorings and signalling systems, from fouling.

The compounds of formula (I) and compositions comprising thereof may also be employed for protecting storage goods. Storage goods are understood to mean natural substances of vegetable or animal origin or processed products thereof which are of natural origin, and for which long-term protection is desired. Storage goods of vegetable origin, for example plants or plant parts, such as stems, leaves, tubers, seeds, fruits, grains, may be protected freshly harvested or after processing by (pre)drying, moistening, comminuting, grinding, pressing or roasting. Storage goods also include timber, both unprocessed, such as construction timber, electricity poles and barriers, or in the form of finished products, such as furniture. Storage goods of animal origin are, for example, hides, leather, furs and hairs. The compounds of formula (I) and compositions comprising thereof may prevent adverse effects, such as rotting, decay, discoloration, decoloration or formation of mould.

Seed Treatment

The compounds of formula (I) and compositions comprising thereof may also be used to protect seeds from unwanted microorganisms, such as phytopathogenic microorganisms, for instance phytopathogenic fungi or phytopathogenic oomycetes. The term seed(s) as used herein include dormant seeds, primed seeds, pregerminated seeds and seeds with emerged roots and leaves.

Thus, the present invention also relates to a method for protecting seeds from unwanted microorganisms which comprises the step of treating the seeds with the compounds of formula (I) and compositions comprising thereof.

The treatment of seeds with the compounds of formula (I) and compositions comprising thereof protects the seeds from phytopathogenic microorganisms, but also protects the germinating seeds, the emerging seedlings and the plants after emergence from the treated seeds. Therefore, the present invention also relates to a method for protecting seeds, germinating seeds and emerging seedlings.

The seeds treatment may be performed prior to sowing, at the time of sowing or shortly thereafter.

When the seeds treatment is performed prior to sowing (e.g. so-called on-seed applications), the seeds treatment may be performed as follows: the seeds may be placed into a mixer with a desired amount of the compounds of formula (I) or compositions comprising thereof, the seeds and the compounds of formula (I) or compositions comprising thereof are mixed until an homogeneous distribution on seeds is achieved. If appropriate, the seeds may then be dried.

The invention also relates to seeds coated with the compounds of formula (I) or compositions comprising thereof.

Preferably, the seeds are treated in a state in which it is sufficiently stable for no damage to occur in the course of treatment. In general, seeds can be treated at any time between harvest and shortly after sowing. It is customary to use seeds which have been separated from the plant and freed from cobs, shells, stalks, coats, hairs or the flesh of the fruits. For example, it is possible to use seeds which have been harvested, cleaned and dried down to a moisture content of less than 15% by weight. Alternatively, it is also possible to use seeds which, after drying, for example, have been treated with water and then dried again, or seeds just after priming, or seeds stored in primed conditions or pre-germinated seeds, or seeds sown on nursery trays, tapes or paper.

The amount of the compounds of formula (I) or compositions comprising thereof applied to the seeds is typically such that the germination of the seed is not impaired, or that the resulting plant is not damaged. This must be ensured particularly in case the the compounds of formula (I) would exhibit phytotoxic effects at certain application rates. The intrinsic phenotypes of transgenic plants should also be taken into consideration when determining the amount of the compounds of formula (I) to be applied to the seed in order to achieve optimum seed and germinating plant protection with a minimum amount of compound being employed.

The compounds of formula (I) can be applied as such, directly to the seeds, i.e. without the use of any other components and without having been diluted. Also a composition comprising one or more compounds of formula (I) can be applied to the seeds.

The compounds of formula (I) and compositions comprising thereof are suitable for protecting seeds of any plant variety. Preferred seeds are that of cereals (such as wheat, barley, rye, millet, triticale, and oats), oilseed rape, maize, cotton, soybean, rice, potatoes, sunflower, beans, coffee, peas, beet (e.g. sugar beet and fodder beet), peanut, vegetables (such as tomato, cucumber, onions and lettuce), lawns and ornamental plants. More preferred are seeds of wheat, soybean, oilseed rape, maize and rice.

The compounds of formula (I) and compositions comprising thereof may be used for treating transgenic seeds, in particular seeds of plants capable of expressing a polypeptide or protein which acts against pests, herbicidal damage or abiotic stress, thereby increasing the protective effect. Seeds of plants capable of expressing a polypeptide or protein which acts against pests, herbicidal damage or abiotic stress may contain at least one heterologous gene which allows the expression of said polypeptide or protein. These heterologous genes in transgenic seeds may originate, for example, from microorganisms of the speciesBacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, GlomusorGliocladium. These heterologous genes preferably originate fromBacillussp., in which case the gene product is effective against the European corn borer and/or the Western corn rootworm. Particularly preferably, the heterologous genes originate fromBacillus thuringiensis.

Application

The compounds of formula (I) can be applied as such, or for example in the form of as ready-to-use solutions, emulsions, water- or oil-based suspensions, powders, wettable powders, pastes, soluble powders, dusts, soluble granules, granules for broadcasting, suspoemulsion concentrates, natural products impregnated with the compounds of formula (I), synthetic substances impregnated with the compounds of formula (I), fertilizers or microencapsulations in polymeric substances.

Application is accomplished in a customary manner, for example by watering, spraying, atomizing, broadcasting, dusting, foaming, spreading-on and the like. It is also possible to deploy the compounds of formula (I) by the ultra-low volume method, via a drip irrigation system or drench application, to apply it in-furrow or to inject it into the soil stem or trunk. It is further possible to apply the compounds of formula (I) by means of a wound seal, paint or other wound dressing.

The effective and plant-compatible amount of the compound(s) of formula (I) which is applied to the plants, plant parts, fruits, seeds or soil will depend on various factors, such as the compound/composition employed, the subject of the treatment (plant, plant part, fruit, seed or soil), the type of treatment (dusting, spraying, seed dressing), the purpose of the treatment (curative and protective), the type of microorganisms, the development stage of the microorganisms, the sensitivity of the microorganisms, the crop growth stage and the environmental conditions.

When the compounds of formula (I) are used as a fungicide, the application rates can vary within a relatively wide range, depending on the kind of application. For the treatment of plant parts, such as leaves, the application rate may range from 0.1 to 10 000 g/ha, preferably from 10 to 1000 g/ha, more preferably from 50 to 300 g/ha (in the case of application by watering or dripping, it is even possible to reduce the application rate, especially when inert substrates such as rockwool or perlite are used). For the treatment of seeds, the application rate may range from 0.1 to 200 g per 100 kg of seeds, preferably from 1 to 150 g per 100 kg of seeds, more preferably from 2.5 to 25 g per 100 kg of seeds, even more preferably from 2.5 to 12.5 g per 100 kg of seeds. For the treatment of soil, the application rate may range from 0.1 to 10 000 g/ha, preferably from 1 to 5000 g/ha.

These application rates are merely examples and are not intended to limit the scope of the present invention.

Aspects of the present teaching may be further understood in light of the following examples, which should not be construed as limiting the scope of the present teaching in any way.

EXAMPLES

Table 1 illustrates in a non-limiting manner examples of compounds of formula (I) according to the invention:

The compounds of formula (I) which are mentioned in table 1 hereinbelow were prepared in accordance with the procedures detailed hereinbelow in connection with specific examples and with the general description of the processes herein disclosed.

In table 1, unless otherwise specified, M+H (Apcl+) means the molecular ion peak plus 1 a.m.u. (atomic mass unit) as observed in mass spectroscopy via positive atmospheric pressure chemical ionisation.

In table 1, the log P values were determined in accordance with EEC Directive 79/831 Annex V.A8 by HPLC (High Performance Liquid Chromatography) on a reversed-phase column (C 18), using the method described below:

Calibration was carried out using unbranched alkan-2-ones (comprising 3 to 16 carbon atoms) with known log P values (determination of the log P values by the retention times using linear interpolation between two successive alkanones). lambda-max-values were determined using UV-spectra from 200 nm to 400 nm and the peak values of the chromatographic signals.

In table 1, # denotes the point of attachement of the SiR1R2R3group.

Table 2 illustrates in a non-limiting manner examples of compounds of formula (IIa) according to the invention as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

In table 2, M+H (Apcl+) and log P are defined as for table 1.

Table 3 illustrates in a non-limiting manner examples of compounds of formula (lIb) according to the invention as well as their acceptable salts:

Wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

In table 3, M+H (Apcl+) and log P are defined as for table 1.

Table 4 illustrates in a non-limiting manner examples of compounds of formula (IIc) according to the invention as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

In table 4, M+H (Apcl+) and log P are defined as for table 1.

Table 5 illustrates in a non-limiting manner examples of compounds of formula (IId) according to the invention as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

In table 5, M+H (Apcl+) and IogP are defined as for table 1.

Table 6 illustrates in a non-limiting manner examples of compounds of formula (lie) according to the invention as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

In table 6, M+H (Apcl+) and log P are defined as for table 1.

Table 7 illustrates in a non-limiting manner examples of compounds of formula (IIf) according to the invention as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C, Q2represents O, S or NR7, R7represents a hydrogen atom or a C1-C6-alkyl group, and U1arepresents a chlorine atom, a bromine atom or an iodine atom.

In table 7, M+H (Apcl+) and log P are defined as for table 1.

Table 8 illustrates in a non-limiting manner examples of compounds of formula (VIIa) according to the invention as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U5represents a chlorine atom or a fluorine atom.

In table 8, M+H (Apcl+) and log P are defined as for table 1.

Table 9 illustrates in a non-limiting manner examples of compounds of formula (VIIb) according to the invention as well as their acceptable salts:

wherein L, n, p, X, Y and Z are as herein-defined, A represents a quinolin-3-yl ring or a quinoxalin-2-yl ring, Q1represents C and U5represents a chlorine atom or a fluorine atom.

In table 9, M+H (Apcl+) and log P are defined as for table 1.

Table 10 provides the NMR data (1H) of a selected number of compounds from table 1.

The1H-NMR data of selected examples are stated in the form of1H-NMR peak lists. For each signal peak, the λ value in ppm and the signal intensity in brackets are listed.

Intensity of sharp signals correlates with the height of the signals in a printed example of a NMR spectrum in cm and shows the real relations of signal intensities. From broad signals several peaks or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown.

The1H-NMR peak lists are similar to classical1H-NMR prints and contain therefore usually all peaks, which are listed at classical NMR-interpretation. Additionally they can show like classical1H-NMR prints signals of solvents, stereoisomers of the target compounds, which are also object of the invention, and/or peaks of impurities. To show compound signals in the delta-range of solvents and/or water the usual peaks of solvents, for example peaks of DMSO in d6-DMSO and the peak of water are shown in our1H-NMR peak lists and have usually on average a high intensity.

The peaks of stereoisomers of the target compounds and/or peaks of impurities have usually on average a lower intensity than the peaks of target compounds (for example with a purity >90%). Such stereoisomers and/or impurities can be typical for the specific preparation process. Therefore their peaks can help to recognize the reproduction of our preparation process via “side-products-fingerprints”.

An expert, who calculates the peaks of the target compounds with known methods (MestreC, ACD-simulation, but also with empirically evaluated expectation values), can isolate the peaks of the target compounds as needed optionally using additional intensity filters. This isolation would be similar to relevant peak picking at classical1H-NMR interpretation.

Further details of NMR-data description with peak lists can be found in the publication “Citation of NMR Peaklist Data within Patent Applications” of the Research Disclosure Database Number 564025.

PREPARATION EXAMPLES

Step 1: Preparation of 3-[(3-bromo-2-fluoropyridin-4-yl)oxy]quinoline

To a mixture of 315 mg (2.10 mmol) of quinolin-3-ol and 860 mg (4.21 mmol) of 3-bromo-2,4-difluoropyridine dissolved in 30 mL of DMF [dimethylformamide] were added 754 mg (2.31 mmol) of cesium carbonate. The reaction mixture was stirred at room temperature for 7 hours. The reaction mixture was diluted by water, extracted by ethyl acetate and the organic extracts were dried over magnesium sulfate. The organic phase was concentrated under vacuum and the residue was purified by column chromatography on silica gel (gradient n-heptane/ethyl acetate) to yield 628 mg (93% yield) of 3-[(3-bromo-2-fluoropyridin-4-yl)oxy]quinoline as a white-off solid. Log P=2.96. Mass (M+H)=319.

Step 2: Preparation of 3-{[2-fluoro-3-(trimethylsilyl)pyridin-4-yl]oxy}quinoline

In a dried Radleys™ vial under argon, a mixture of 100 mg (0.31 mmol) of 3-[(3-bromo-2-fluoropyridin-4-yl)oxy]quinoline, 94 mg (0.62 mmol) of 1,1,1,2,2,2-hexamethyldisilane, 9.6 mg (0.032 mmol) of biphenyl-2-yl(di-tert-butyl)phosphine [Johnphos], 2.8 mg (0.016 mmol) of palladium (II) chloride and 0.16 mL (0.94 mmol) of N,N-diisopropylethylamine in 5 mL of dry NMP [N-methylpyrrolidone], was heated at 80° C. for 8 hours. The cooled reaction mixture was diluted by water and extracted by ethyl acetate. The organic extracts were washed twice by a satured aqueous solution of LiCI and dried over magnesium sulfate. The organic phase was concentrated under vacuum to yield 152 mg of a residue as a dark brown oil. Purification by preparative HPLC (gradient acetonitrile/water+0.1% HCO2H) yields 19 mg (19% yield) of 3-{[2-fluoro-3-(trimethylsilyl)pyridin-4-yl]oxy}quinoline. Log P=4.08. Mass (M+H)=313.

To a mixture of 700 mg (4.82 mmol) of quinolin-3-ol and 1.13 g (9.64 mmol) of 2,4-difluoropyridine in solution in 30 mL of DMF, was added 1.72 g (5.30 mmol) of cesium carbonate. The reaction mixture was heated at 110° C. for 4 hours. The reaction mixture was brought up to room temperature, diluted by water and extracted by ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated under vacuum to give 1.15 g of the crude product as an orange oil. The residue was purified by column chromatography on silica gel (gradient n-heptane/ethyl acetate) to yield 1.02 g (86% yield) of 3-[(2-fluoropyridin-4-yl)oxy]quinoline as a pale yellow solid. Log P=2.25. Mass (M+H)=241.

Step 2: Preparation of 3-({3-[benzyl(dimethyl)silyl]-2-fluoropyridin-4-yl}oxy)quinoline

To a solution of 100 mg (0.41 mmol) of 3-[(2-fluoropyridin-4-yl)oxy]quinoline in 4 mL of tetrahydrofuran [THF] were added 95 mg (0.50 mmol) of benzyl(chloro)dimethylsilane in solution in 4 mL of THF. The reaction mixture was cooled to −78° C. and 0.229 mL of a 2 M solution of lithium diisopropylamine [LDA] in THF was slowly added. The reaction mixture was further stirred at −78° C. for 4 hours. The cooled reaction was diluted by water and extracted by ethyl acetate. The organic phase was washed by water, dried over magnesium sulfate and concentrated under vacuum to give 285 mg of the crude product as an oil. This residue was purified by preparative HPLC (gradient acetonitrile/water+0.1% HCO2H) to yield 51 mg (28% yield) of 3-({3-[benzyl(dimethyl)silyl]-2-fluoropyridin-4-yl}oxy)quinoline. Log P=4.78. Mass (M+H)=389.

In a 5 mL microwave vial under argon, 100 mg (0.44 mmol) of (7,8-difluoro-2-methylquinolin-3-yl)boronic acid were dissolved together with 102 mg (0.44 mmol) of [3-(trimethylsilyl)-2-thienyl]methyl acetate in 2 mL of 1,2-dimethoxyethane. 155 mg (1.12 mmol) of potassium carbonate dissolved in 1 mL of water and 15 mg (0.022 mmol) of dichlorobis(triphenylphosphine)palladium(II) were added and the mixture heated under microwave at 120° C. for 15 min. The cooled reaction mixture was filtered over a 2 g basic alumina and 2 g silica gel cartridge. The cartridge was further washed by dichloromethane and the organic phase was concentrated under vacuum. The residue was purified by preparative HPLC (gradient acetonitrile/water+0.1% HCO2H) to yield 18 mg (11% yield) of 7,8-difluoro-2-methyl-3-{[3-(trimethyl-silyl)-2-thienyl]methyl}quinoline. Log P=5.25. Mass (M+H)=348.

To a suspension of 48 mg (0.36 mmol) of 2-methyl-1H-benzimidazole and 75 mg (0.54 mmol) of potassium carbonate in 2 mL of dry DMF, was added dropwise a solution of 106 mg (0.36 mmol) of [2-(bromomethyl)-3-thienyl](trimethyl)silane dissolved in 1 mL of DMF. The reaction mixture was stirred for 4 hours at room temperature. The reaction mixture was diluted by water and brine and extracted three times by ethyl acetate. The combined extracts were washed by water, dried over sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography on silica gel (gradient n-heptane/ethyl acetate) to yield 32 mg (28% yield) of 2-methyl-1-{[3-(trimethylsilyl)-2-thienyl]methyl}-1H-benzimidazole. Log P=2.13. Mass (M+H)=301.

Biological Data

Example A: In Vitro Cell Test onPyricularia Oryzae

The tested compounds were solubilized in dimethyl sulfoxide and the solution used to prepare the required range of concentrations. The final concentration of dimethyl sulfoxide used in the assay was ≤1%.

A spore suspension ofPyricularia oryzaewas prepared and diluted to the desired spore density.

The compounds were evaluated for their ability to inhibit spore germination and mycelium growth in liquid culture assay. The compounds were added in the desired concentration to the culture medium with spores. After 5 days incubation, fungi-toxicity of compounds was determined by spectrometric measurement of mycelium growth. Inhibition of fungal growth was determined by comparing the absorbance values in wells containing the tested compound with the absorbance in control wells without the tested compound.

In this test the following compounds according to the invention showed efficacy between 80% and 89% at a concentration of 20 ppm of active ingredient: I.11; I.19

In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 20 ppm of active ingredient: I.03; I.05; I.06; I.07; I.08; I.09; I.12; I.13; I.17; I.24; I.25

Example B: In Vitro Cell Test onLeptnosphaeria nodorum

The tested compounds were solubilized in dimethyl sulfoxide and the solution used to prepare the required range of concentrations. The final concentration of dimethyl sulfoxide used in the assay was ≤1%.

A spore suspension ofLeptnosphaeria nodorumwas prepared and diluted to the desired spore density.

The compounds were evaluated for their ability to inhibit spore germination and mycelium growth in liquid culture assay. The compounds were added in the desired concentration to the culture medium with spores. After 5 days incubation, fungi-toxicity of compounds was determined by spectrometric measurement of mycelium growth. Inhibition of fungal growth was determined by comparing the absorbance values in wells containing the tested compound with the absorbance in control wells without the tested compound.

In this test the following compounds according to the invention showed efficacy between 70% and 79% at a concentration of 20 ppm of active ingredient: I.10; I.11

In this test the following compounds according to the invention showed efficacy between 80% and 89% at a concentration of 20 ppm of active ingredient: I.02; I.06; I.08; I.12; I.13; I.20; I.22

In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 20 ppm of active ingredient: I.03; I.04; I.05; I.07; I.09; I.17; I.19; I.24; I.25

Example C: In Vitro Cell Test onColletotrichum lindemuthianum

The tested compounds were solubilized in dimethyl sulfoxide and the solution used to prepare the required range of concentrations. The final concentration of dimethyl sulfoxide used in the assay was ≤1%.

A spore suspension ofColletotrichum lindemuthianumwas prepared and diluted to the desired spore density.

The compounds were evaluated for their ability to inhibit spore germination and mycelium growth in liquid culture assay. The compounds were added in the desired concentration to the culture medium with spores. After 6 days incubation, fungi-toxicity of compounds was determined by spectrometric measurement of mycelium growth. Inhibition of fungal growth was determined by comparing the absorbance values in wells containing the the tested compound with the absorbance in control wells without the tested compound.

In this test the following compounds according to the invention showed efficacy between 70% and 79% at a concentration of 20 ppm of active ingredient: I.19

In this test the following compounds according to the invention showed efficacy between 80% and 89% at a concentration of 20 ppm of active ingredient: I.06; I.12

In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 20 ppm of active ingredient: I.03; I.04; I.05; I.07; I.08; I.09; I.10; I.11; I.13; I.17; I.24; I.25

Solvent: 5% by volume of dimethyl sulfoxide10% by volume of acetone

Emulsifier: 1 μL of Tween® 80 per mg of active ingredient

The compounds to be tested were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetone//Tween® 80 and then diluted in water to the desired concentration.

The young plants of gherkin were treated by spraying the compound prepared as described above.

Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween® 80.

After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension ofBotrytis cinereaspores. The contaminated gherkin plants were incubated for 4 to 5 days at 17° C. and at 90% relative humidity.

The test was evaluated 4 to 5 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease is observed.

In this test the following compound according to the invention showed efficacy between 80% and 89% at a concentration of 500 ppm of active ingredient: I.12

In this test the following compound according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I.19

Example E: In Vivo Preventive Test onSphaerotheca fuliginea(Powdery Mildew on Cucurbits)

Solvent: 5% by volume of dimethyl sulfoxide10% by volume of acetone

Emulsifier: 1 μL of Tween® 80 per mg of active ingredient

The compounds to be tested were made soluble and homogenized in a mixture of dimethyl sulfoxide/acetonel/Tween® 80 and then diluted in water to the desired concentration.

The young plants of gherkin were treated by spraying the compound prepared as described above. Control plants were treated only with an aqueous solution of acetone/dimethyl sulfoxide/Tween® 80. After 24 hours, the plants were contaminated by spraying the leaves with an aqueous suspension ofSphaerotheca fuligineaspores. The contaminated gherkin plants were incubated for 8 days at 20° C. and at 70-80% relative humidity.

The test was evaluated 8 days after the inoculation. 0% means an efficacy which corresponds to that of the control plants while an efficacy of 100% means that no disease is observed.

In this test the following compounds according to the invention showed efficacy between 70% and 79% at a concentration of 500 ppm of active ingredient: I.07; I.19

In this test the following compounds according to the invention showed efficacy between 90% and 100% at a concentration of 500 ppm of active ingredient: I.06; I.17