WO2014154530A1

WO2014154530A1 - Microbiocidal pyrazole derivatives

Info

Publication number: WO2014154530A1
Application number: PCT/EP2014/055396
Authority: WO
Inventors: Clemens Lamberth; Stephan Trah; Laura Quaranta; Fredrik Emil Malcolm Cederbaum; Martin Pouliot; Werner Zambach; Farhan BOU HAMDAN; Atul Mahajan
Original assignee: Syngenta Participations AG
Current assignee: Syngenta Participations AG
Priority date: 2013-03-25
Filing date: 2014-03-18
Publication date: 2014-10-02
Anticipated expiration: 2015-09-25

Abstract

Compounds of the formula (I) wherein the substituents are as defined in claim 1, are useful as pesticides.

Description

Microbiocidal Pyrazole Derivatives

The present invention relates to microbiocidal pyrazole derivatives, e.g. as active ingredients, which have microbiocidal activity, in particular fungicidal activity. The invention also relates to preparation of these pyrazole derivatives, to pyrazole derivatives used as intermediates in the preparation of these pyrazole derivatives, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the pyrazole derivatives, to preparation of these compositions and to use of the pyrazole derivatives or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi.

Certain compounds for use as fungicides are described in WO 2007/014290, WO 2008/013622, WO 2008/013925, WO 2008/091580, WO 2008/091594 and WO

2009/055514.

The present invention provides compounds of formula I:

wherein,

G¹ and G² are independently O or S;

T is CR¹⁴ or N;

Y¹ and Y² are independently CR¹⁵ or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are CrC₄alkyl, CrC₄haloalkyl or C₃-C₅cycloalkyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, halogen, cyano, CrC₄alkyl, Ci- C₄alkoxy, d-C₄haloalkyl, C₃-C₅cycloalkyl or Ci-C₄alkylthio;

R⁹ is aryl or heteroaryl, both optionally substituted by one or more R¹⁶;

R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen, cyano, Ci-C₄alkyl, Ci- C haloalkyl, C₃-C₅cycloalkyl, aryl or heteroaryl, the aryl or heteroaryl optionally substituted by one or more R¹⁶; or

R¹⁰ and R¹¹ together with the carbon atom to which they are attached, independently form a saturated or partially unsaturated three- to five-membered alicyclic ring, optionally substituted by halogen, cyano, CrC₄alkyl, Ci-C₄alkoxy or Ci-C₄haloalkyl;

R¹³ is C C alkyl, Ci-C₄haloalkyl, C₃-C₅cycloalkyl, Ci-C₄alkylcarbonyl, aryl, heteroaryl, the aryl or heteroaryl optionally substituted by one or more R¹⁶; R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

R¹⁶ is halogen, cyano, hydroxyl, amino, formyl, Ci-C₄alkyl, Ci-C₄haloalkyl, C₃-C₅cycloalkyl, C₂-C₅alkenyl, C₂-C₅haloalkenyl, C₂-C₅alkynyl, C₂-C₅haloalkynyl, CrC₄alkoxy, Ci- C₄haloalkoxy, C₃-C₅cycloalkoxy, C₃-C₅alkenyloxy, C₃-C₅haloalkenyloxy, C₃-C₅alkynyloxy, C₃- C₅haloalkynyloxy, Ci-C₄alkylamino, Ci-C₄dialkylamino, Ci-C₄alkylcarbonyl, Ci- C₄haloalkylcarbonyl, C₃-C₅cycloalkylcarbonyl, CrC₄alkylcarbonyl 0-Ci-C₄alkyloxime, Ci- C₄haloalkylcarbonyl 0-Ci-C₄alkyloxime, C₃-C₅cycloalkylcarbonyl 0-Ci-C₄alkyloxime, Ci- C₄alkylcarbonyloxy, Ci-C₄haloalkylcarbonyloxy, C₃-C₅cycloalkylcarbonyloxy, Ci- C₄alkoxycarbonyl, CrC₄haloalkoxycarbonyl, C₃-C₅cycloalkoxycarbonyl, aryl, heteroaryl, arylCrC₄alkyl or heteroarylCi-C₄alkyl;

or a salt or a N-oxide thereof.

Where substituents are indicated as being optionally substituted, this means that they may or may not carry one or more identical or different substituents, e.g. one to five substituents, e.g. one to three substituents. Normally not more than three such optional substituents are present at the same time. Where a group is indicated as being substituted, e.g. alkyl, unless stated otherwise this includes those groups that are part of other groups, e.g. the alkyl in alkylthio.

The term "halogen" refers to fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

Alkyl substituents may be straight-chained or branched. Alkyl on its own or as part of another substituent is, depending upon the number of carbon atoms mentioned, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl and the isomers thereof, for example, iso- propyl, iso-butyl, sec-butyl, tert-butyl or iso-amyl.

Alkenyl substituents can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configu ration. Examples are vinyl and allyl. The alkenyl groups are preferably C₂-C₆, more preferably C₂-C₄ and most preferably C₂-C₃ alkenyl groups.

Alkynyl substituents can be in the form of straight or branched chains. Examples are ethynyl and propargyl. The alkynyl groups are preferably C₂-C₆, more preferably C₂-C₄ and most preferably C₂-C₃ alkynyl groups.

Haloalkyl groups may contain one or more identical or different halogen atoms and, for example, may stand for CH₂CI, CHCI₂, CCI₃, CH₂F, CHF₂, CF₃, CF₃CH₂, CH₃CF₂, CF₃CF₂ or CCI₃CCI₂.

Haloalkenyl groups are alkenyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 2,2-difluorovinyl or 1 ,2- dichloro-2-fluoro-vinyl. Haloalkynyl groups are alkynyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, 1-chloro-prop-2-ynyl.

Alkoxy means a radical -OR, where R is alkyl, e.g. as defined above. Alkoxy groups include, but are not limited to, methoxy, ethoxy, 1 -methylethoxy, propoxy, butoxy, 1 - methylpropoxy and 2-methylpropoxy.

Cyano means a -CN group.

Amino means an NH₂ group.

Hydroxyl or hydroxy stands for a -OH group.

Aryl means a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.

Heteroaryl stands for aromatic ring systems comprising mono-, bi- or tricyclic systems wherein at least one oxygen, nitrogen or sulfur atom is present as a ring member. Monocyclic and bicyclic aromatic ring systems are preferred, monocyclic ring systems are more preferred. For example, monocyclic heteoraryl may be a 5- to 7-membered aromatic ring containing one to three heteroatoms selected from oxygen, nitrogen and sulfur, more preferably selected from nitrogen and sulfur. Bicyclic heteroaryl may be a 9- to 11-membered bicyclic ring containing one to five heteroatoms, preferably one to three heteroatoms, selected from oxygen, nitrogen and sulfur. Examples are furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, tetrazinyl, indolyl,

benzothiophenyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, imiazothiazoyl, quinolinyl, quinoxalinyl, isoquinolinyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl and naphthyridinyl, preferably pyridyl, pyrazinyl, pyridazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, furanyl, thienyl thiazolyl or thiadiazolyl. Heteroaryl rings do not contain adjacent oxygen ring atoms, adjacent sulfur ring atoms or adjacent oxygen and sulfur ring atoms. A link to a heteroaryl group can be via a carbon atom or via a nitrogen atom.

The presence of one or more possible asymmetric carbon atoms in a compound of formula I means that the compounds may occur in optically isomeric forms, i.e. enantiomeric or diastereomeric forms. Also atropisomers may occur as a result of restricted rotation about a single bond. Formula I is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula I. Likewise, formula I is intended to include all possible tautomers. The present invention includes all possible tautomeric forms for a compound of formula I.

In each case, the compounds of formula I according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form. N-oxides are oxidized forms of tertiary amines or oxidized forms of nitrogen containing heteroaromatic compounds. They are described for instance in the book "Heterocyclic N- oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.

The following list provides definitions, including preferred definitions, for substituents R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸, G¹, G², T, Y¹, Y², n and p with reference to compounds of formula I and other compounds of the invention carrying the same substituents. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.

G¹ and G² are independently 0 or S.

G¹ is preferably O.

G² is preferably S.

T is CR¹⁴ or N, preferably CH or N, more preferably CH.

Y¹ and Y² are independently CR¹⁵ or N.

Y¹ is preferably CH or N, more preferably N.

Y² is preferably CH or N; more preferably CH.

n is 1 or 2, preferably 2.

p is 1 or 2, providing that when n is 2, p is 1 , preferably p is 1.

Preferably, p is 1 and n is 2.

R¹ and R² each independently are Ci-C₄alkyl, d-C₄haloalkyl or C₃-C₅cycloalkyl.

Preferably R¹ and R² are each independently methyl or halomethyl, more preferably methyl, difluoromethyl or trifluoromethyl.

Preferably R¹ is difluoromethyl or trifluoromethyl. Preferably R² is methyl or difluoromethyl. In one group of compounds R¹ is trifluoromethyl and R² is methyl. In another group of compounds R¹ and R² are both difluoromethyl.

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, halogen, cyano, C C₄alkyl, Ci-C₄alkoxy, CrC₄haloalkyl, C₃-C₅cycloalkyl or Ci-C₄alkylthio; preferably hydrogen, halogen, methyl, halomethyl or methylthio, more preferably hydrogen or methyl, even more preferably hydrogen.

R⁹ is aryl or heteroaryl, both optionally substituted by one or more R¹⁶; preferably phenyl which is optionally substituted by one or more R¹⁶; more preferably phenyl, which is substituted by hydrogen, halogen, cyano, Ci-C₄alkyl, CrC₄haloalkyl or C₃-C₅alkynyloxy, even more preferably phenyl, which is substituted by hydrogen, halogen, or C₃-C₅alkynyloxy.

R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen, cyano, Ci-C₄alkyl, Ci- C haloalkyl, C₃-C₅cycloalkyl, aryl or heteroaryl; preferably hydrogen, halogen, Ci-C₄alkyl, Ci- C₄haloalkyl or C₃-C₅cycloalkyl; more preferably hydrogen, halogen or CrC₄alkyl, even more preferably hydrogen or Ci-C₄alkyl. R¹³ is CrC₄alkyl, Ci-C₄haloalkyl, C₃-C₅cycloalkyl, Ci-C₄alkylcarbonyl, aryl, heteroaryl, the aryl or heteroaryl optionally substituted by one or more R¹⁶; preferably CrC₄alkyl, Ci- C₄haloalkyl, C₃-C₅cycloalkyl or phenyl which is optionally substituted by one or more R¹⁶; more preferably CrC₄alkyl or C₃-C₅cycloalkyl.

R¹⁴ is hydrogen, halogen or hydroxyl; preferably hydrogen or hydroxyl, more preferably hydrogen.

R¹⁵ is hydrogen, halogen or cyano; preferably hydrogen or cyano, more preferably hydrogen.

Preferably the compound of formula I is a compound wherein:

G¹ is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are methyl or halomethyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, halogen, cyano, CrC₄alkyl, Ci- C₄alkoxy, Ci-C₄haloalkyl, C₃-C₅cycloalkyl or CrC₄alkylthio;

R⁹ is aryl or heteroaryl, both optionally substituted by one or more R¹⁶;

R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen, cyano, CrC₄alkyl, Ci- C₄haloalkyl, C₃-C₅cycloalkyl, aryl or heteroaryl; or

R¹⁰ and R¹¹ together with the carbon atom to which they are attached, independently form a saturated or partially unsaturated three- to five-membered alicyclic ring, optionally substituted by halogen, cyano, CrC₄alkyl, d-C₄alkoxy or CrC₄haloalkyl;

R¹³ is C C₄alkyl, CrC₄haloalkyl, C₃-C₅cycloalkyl, Ci-C₄alkylcarbonyl, aryl, heteroaryl, the aryl or heteroaryl optionally substituted by one or more R¹⁶;

R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

or a salt or a N-oxide thereof.

Preferably the compound of formula I is a compound wherein:

G is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are methyl or halomethyl; R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, halogen, methyl, halomethyl or methylthio;

R⁹ is phenyl which is optionally substituted by one or more R¹⁵;

R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen, Ci-C₄alkyl, CrC₄haloalkyl or C3- C₅cycloalkyl;

R¹³ is C C₄alkyl, Ci-C₄haloalkyl, C3-C₅cycloalkyl or phenyl which is optionally substituted by one or more R¹⁶;

R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

or a salt or a N-oxide thereof.

Preferably the compound of formula I is a compound wherein:

G¹ is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are methyl or halomethyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen or methyl;

R⁹ is phenyl, which is substituted by hydrogen, halogen, cyano, CrC₄alkyl, CrC₄haloalkyl or C₃-C₅alkynyloxy.

R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen or d-C₄alkyl;

R¹³ is C C₄alkyl or C₃-C₅cycloalkyl;

R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

or a salt or a N-oxide thereof.

Preferably the compound of formula I is a compound wherein:

G¹ is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are methyl, difluoromethyl or trifluoromethyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are hydrogen;

R⁹ is phenyl, which is substituted by hydrogen, halogen or C3-C₅alkynyloxy.

R¹⁰, R¹¹ and R¹² each independently are hydrogen or CrC4alkyl;

R¹³ is CrC₄alkyl or C₃-C₅cycloalkyl; R is hydrogen or hydroxyl;

R¹⁵ is hydrogen or cyano;

or a salt or a N-oxide thereof.

Preferably the compound of formula I is a compound wherein G¹ is O, G² is S, T is CH, Y¹ is N, and Y² is CH.

Preferably the compound of formula I is a compound wherein R¹ and R² each independently are methyl, difluoromethyl or trifluoromethyl and R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, or methyl, and preferably hydrogen.

For the avoidance of doubt, when n is 1 and p is 1 compounds of formula I have the

in which R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹ and Y² have the definitions as described for formula I.

When n is 2 and p is 1 compounds of formula I have the formula according to formula l

When n is 1 and p is 2, compounds of formula I have the formula according to formula l-

in which R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹ and Y² have the definitions as described for formula I. The invention also relates to compounds of formula l-a, formula l-b and formula l-c as shown above.

in which R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹ and Y² have the definitions as described for formula I. Preferred definitions of R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R^! R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹ and Y² are as defined for formula I.

in which R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³ and T have the definitions as described for formula I. Preferred definitions of R¹, R², R³, R⁴, R⁵, R⁵, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³ and T are as defined for formula I.

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹, Y², n and p have the definition as described for formula I . Preferred definitions of R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹, Y², n and p are as defined for formula I .

The invention also relates to compounds of formula l-g:

in which R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹, Y², n and p have the definitions as described for formula I. Preferred definitions of R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹, Y², n and p are as defined for formula I.

The invention also relates to compounds of formula l-h:

in which R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹, Y², n and p have the definitions as described for formula I. Preferred definitions of R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R ³, G¹, G², T, Y¹, Y², n and p are as defined for formula I.

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y² , n and p are as defined for a compound of formula I. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y² , n and p are as defined for formula I.

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y² , n and p are as defined for a compound of formula I and E is a protecting group, such as C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or iert-butoxycarbonyl. These compounds, including salts and N-oxides thereof, are useful as intermediates in the synthesis of compounds of formula I. Preferred definitions of R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R ⁰, R¹¹, R ², R¹³, G², T, Y¹, Y² , n and p are as defined for formula I.

Compounds of the present invention can be made as shown in the following schemes.

The compounds of formula I, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G¹, G², T, Y¹, Y², n and p are as defined for formula I can be obtained by transformation of a compound of formula IV, wherein R¹, R² and G¹ are as defined for formula I and R¹⁷ is hydroxy, halogen, preferably fluoro, chloro or bromo, or alkoxy, such as methoxy or ethoxy, with a compound of formula II, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R ⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y², n and p are as defined for formula I, and a base or an activating agent. This is shown in Scheme 1.

Scheme 1

The compounds of formula II, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y², n and p are as defined for formula I can be obtained by transformation of a compound of formula III, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R ⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y², n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or tert- butoxycarbonyl, with a deprotecting agent such as a base, an acid or a hydrogenation system such as H₂/Pd. This is shown in Scheme 2.

Scheme 2

(III) (ii) The compounds of formula III, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y², n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or fert-butoxycarbonyl, can be obtained by transformation of a compound of formula V, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, G², T, Y¹, Y², n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or ferf-butoxycarbonyl, with a compound of formula VI, wherein R⁹, R¹⁰, R¹¹, R¹² and R¹³ are as defined for formula I, and hydroxylamine and sodium hypochlorite. This is shown in Scheme 3. Scheme 3

Alternatively, the compounds of formula III, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y², n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or ferf-butoxycarbonyl, can be obtained by transformation of a compound of formula VII, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, G², T, Y¹, Y², n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or ierf-butoxycarbonyl, with a compound of formula VI, wherein R⁹, R¹⁰, R¹¹, R¹² and R¹³ are as defined for formula I, and an oxidant such as sodium hypochlorite, /V-chlorosuccinimide or diacetoxyiodobenzene. This is shown in Scheme 4.

Scheme 4

The compounds of formula VII, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, G², T, Y¹, Y², n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or tert- butoxycarbonyl, can be obtained by transformation of a compound of formula V, wherein R³, R⁴, R⁵, R⁵, R⁷, R⁸, G², T, Y¹, Y², n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or ierf-butoxycarbonyl, with hydroxylamine. This is shown in Scheme 5. Scheme 5

as defined for formula I and E is a protecting group such as acetyl, benzyl or tert- butoxycarbonyl, can be obtained by transformation of a compound of formula VIII, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, G², T, Y¹, Y², n and p are as defined for formula I , R¹⁸ is alkoxy, such as methoxy or ethoxy and E¹ is a protecting group such as acetyl, benzyl or tert- butoxycarbonyl, and a reducing agent, such as diisobutyllithium aluminium hydride. This is shown in Scheme 6.

Scheme 6

The compounds of formula VI, wherein R⁹, R¹⁰, R¹¹ , R¹² and R¹³ are as defined for formula I, can be obtained by transformation of a compound of formula IX, wherein R⁹, R¹⁰ and R¹¹ are as defined for formula I and Hal is halogen, preferably chloro or bromo, with a compound of formula X, wherein R¹² and R¹³ are as defined for formula I, and a base. This is shown in Scheme 7.

Scheme 7

(IX) (X) (VI)

The compounds of formula IX, wherein R⁹, R¹⁰ and R ¹ are as defined for formula I and Hal is halogen, preferably chloro or bromo, can be obtained by transformation of a compound of formula XI, wherein R⁹, R ⁰ and R¹¹ are as defined for formula I , and a halogenation agent, such as N-chlorosuccinimid or N-bromosuccinimid. This is shown in Scheme 8. Scheme 8

(XI) (IX)

The compounds of formula X, wherein R¹² and R¹³ are as defined for formula I can be obtained by transformation of a compound of formula XII, wherein R¹² and R¹³ are as defined for formula I, and hydroxylamine. This is shown in Scheme 9.

Scheme 9

(Xll) (X)

Alternatively, the compounds of formula VI, wherein R⁹, R¹⁰, R¹¹, R¹² and R¹³ are as defined for formula I, can be obtained by transformation of a compound of formula XIII, wherein R⁹, R¹⁰ and R¹¹ are as defined for formula I, with a compound of formula XII, wherein R¹² and R are as defined for formula I. This is shown in Scheme 10.

Scheme 10

(XIII) (Xll) (VI)

Alternatively, the compounds of formula III, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, T, Y¹, Y², n and p are as defined for formula I, G² is S and E is a protecting group such as acetyl, benzyl or ierf-butoxycarbonyl, can be obtained by transformation of a compound of formula XIV, wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, T, n and p are as defined for formula I and E is a protecting group such as acetyl, benzyl or ierf-butoxycarbonyl, with a compound of formula XV, wherein R⁹, R¹⁰, R¹¹, R¹² and R¹³ are as defined for formula I and Hal is halogen, preferably chloro or bromo, and a base. This is shown in Scheme 1 1.

Surprisingly, it has now been found that the novel compounds of formula I have, for practical purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.

The compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non-living materials for control of spoilage microorganisms or organisms potentially harmful to man. The novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants. The compounds of formula I can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.

It is also possible to use compounds of formula I as dressing agents for the treatment of plant propagation material, e.g., seed, such as fruits, tubers or grains, or plant cuttings (for example rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil. The propagation material can be treated with a composition comprising a compound of formula I before planting: seed, for example, can be dressed before being sown. The active ingredients according to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.

Furthermore the compounds according to present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood related technical products, in food storage, in hygiene management.

In addition, the invention could be used to protect non-living materials from fungal attack, e.g. lumber, wall boards and paint.

The compounds of formula I are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Alternaria spp.), Basidiomycetes (e.g. Corticium spp., Ceratobasidium spp., Waitea spp., Thanatephorus spp., Rhizoctonia spp., Hemileia spp., Puccinia spp., Phakopsora spp., Ustilago spp., Tilletia spp.), Ascomycetes (e.g. Venturia spp., Blumeria spp., Erysiphe spp., Podosphaera spp., Uncinula spp., Monilinia spp., Sclerotinia spp., Colletotrichum spp., Glomerella spp., Fusarium spp., Gibberella spp., Monographella spp., Phaeosphaeria spp., Mycosphaerella spp., Cercospora 5 spp., Pyrenophora spp., Rhynchosporium spp., Magnaporthe spp., Gaeumannomyces spp., Oculimacula spp., Ramularia spp., Botryotinia spp.) and Oomycetes (e.g. Phytophthora spp., Pythium spp., Plasmopara spp., Peronospora spp., Pseudoperonospora spp. Bremia spp). Outstanding activity is observed against downy mildew (e.g. Plasmopara viticola) and late blight (e.g. Phytophthora infestans). Furthermore, the novel compounds of formula I are

10 effective against phytopathogenic gram negative and gram positive bacteria (e.g.

Xanthomonas spp, Pseudomonas spp, Erwinia amylovora, Ralstonia spp.) and viruses (e.g. tobacco mosaic virus).

Within the scope of present invention, target crops and/or useful plants to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize,

15 sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit

20 (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus,

cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as turf and ornamentals.

The useful plants and / or target crops in accordance with the invention include

25 conventional as well as genetically enhanced or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties. By way of example, suitable genetically enhanced or engineered crop varieties include the Stoneville

30 5599BR cotton and Stoneville 4892BR cotton varieties.

The term "useful plants" and/or "target crops" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate-3-phosphate-synthase)

35 inhibitors, GS (glutamine synthetase) inhibitors or PPO (protoporphyrinogen-oxidase)

inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and

LibertyLink®.

The term "useful plants" and/or "target crops" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.

The term "useful plants" and/or "target crops" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for example, the so-called "pathogenesis-related proteins" (PRPs, see e.g. EP-A-0 392 225). Examples of such antipathogenic substances and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A-0 353 191. The methods of producing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.

The term "locus" of a plant as used herein is intended to embrace the place on which the plants are growing, where the plant propagation materials of the plants are sown or where the plant propagation materials of the plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.

The term "plant propagation material" is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as cuttings or tubers, for example potatoes. There may be mentioned for example seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of plants. Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably "plant propagation material" is understood to denote seeds.

The compounds of formula I may be used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.

Suitable carriers and adjuvants, e.g. for agricultural use, can be solid or liquid and are substances useful in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.

The compounds of formula I are normally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which influence the growth of plants. They can also be selective herbicides or non-selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.

The compounds of formula I may be used in the form of (fungicidal) compositions for controlling or protecting against phytopathogenic microorganisms, comprising as active ingredient at least one compound of formula I or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants.

The invention provides a composition, preferably a fungicidal composition, comprising at least one compound formula I an agriculturally acceptable carrier and optionally an adjuvant. An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art. Preferably said composition may comprise at least one or more pesticidally active compounds, for example an additional fungicidal active ingredient in addition to the compound of formula I.

The compound of formula (I) may be the sole active ingredient of a composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may, in some cases, result in unexpected synergistic activities. Examples of suitable additional active ingredients include the following: Azoxystrobin (131860-33-8), Dimoxystrobin (1 9961-52-4), Enestrobin (238410-1 1-2), Fluoxastrobin (193740-76-0), Kresoxim-methyl (143390-89-0), Metominostrobin (133408-50-1 ), Orysastrobin (248593-16- 0), Picoxystrobin (1 17428-22-5), Pyraclostrobin (175013-18-0), trifloxystrobin (141517-21 -7), Azaconazole (60207-31-0), Bromuconazole (1 16255-48-2), Cyproconazole (94361 -06-5), Difenoconazole (1 19446-68-3), Diniconazole (83657-24-3), Diniconazole-M (83657-18-5), Epoxiconazole (13385-98-8), Fenbuconazole (1 14369-43-6), Fluquinconazole (136426-54- 5), Flusilazole (85509-19-9), Flutriafol (76674-21 -0), Hexaconazole (79983-71 -4), Imazalil (58594-72-2), Imibenconazole (86598-92-7), Ipconazole (125225-28-7), Metconazole (1251 16-23-6), Myclobutanil (88671-89-0), Oxpoconazole (174212-12-5), Pefurazoate (5801 1 -68-0), Penconazole (66246-88-6), Prochloraz (67747-09-5), Propiconazole (60207- 90-1 ), Prothioconazole (178928-70-6), Simeconazole (149508-90-7), Tebuconazole

(107534-96-3), Tetraconazole (1 12281-77-3), Triadimefon (43121-43-3), Triadimenol (55219-65-3), Triflumizole (99387-89-0), Triticonazole (131983-72-7), Diclobutrazol (76738- 62-0), Etaconazole (60207-93-4), Fluconazole (86386-73-4), Fluconazole-cis (112839-32-4), Thiabendazole (148-79-8), Quinconazole (103970-75-8), Fenpiclonil (74738-17-3),

Fludioxonil (131341 -86-1 ), Cyprodinil (121552-61 -2), Mepanipyrim (1 10235-47-7),

Pyrimethanil (531 12-28-0), Aldimorph (91315-15-0), Dodemorph (1593-77-7),

Fenpropimorph (67564-91-4), Tridemorph (81412-43-3), Fenpropidin (67306-00-7),

Spiroxamine (1 18134-30-8), Isopyrazam (881685-58-1 ), Sedaxane (874967-67-6), Bixafen (581809-46-3), Penthiopyrad (183675-82-3), Fluxapyroxad (907204-31 -3), Boscalid (188425- 85-6), Penflufen (494793-67-8), Fluopyram (658066-35-4), Mandipropamid (374726-62-2), Benthiavalicarb (413615-35-7), Dimethomorph (1 10488-70-5), Chlorothalonil (1897-45-6), Fluazinam (79622-59-6), Dithianon (3347-22-6), Metrafenone (220899-03-6), Tricyclazole (41814-78-2), Mefenoxam (70630-17-0), Metalaxyl (57837-19-1 ), Acibenzolar (126448-41 -7) (Acibenzolar-S-methyl (126448-41 -7)), Mancozeb (8018-01 -7), Ametoctradine (865318-97-4) Cyflufenamid (180409-60-3), and Kresoxim-methyl (143390-89-0), Ipconazole (125225-28- 7), Amisulbrom (348635-87-0), Cyflufenamid (180409-60-3), Ethaboxam (16650-77-3), Fluopicolide (2391 10-15-7), Fluthianil (304900-25-2), Isotianil (224049-04-1 ), Proquinazid (189278-12-4), Valiphenal (283159-90-0), 1-methyl-cyclopropene (3100-04-7), Trifloxystrobin (141517-21 -7), Sulfur (7704-34-9), Copper ammoniumcarbonate (CAS 331 13-08-5); Copper oleate (CAS 1 120-44-1 ); Folpet (133-07-3), Quinoxyfen (124495-18-7), Captan (133-06-2), Fenhexamid (126833-17-8), Glufosinate and its salts (51276-47-2, 35597-44-5 (S-isomer)), Glyphosate (1071 -83-6 ) and its salts (69254-40-6 (Diammonium), 34494-04-7

(Dimethylammonium), 38641-94-0 (Isopropylammonium), 40465-66-5 (Monoammonium), 70901-20-1 (Potassium), 70393-85-0 (Sesquisodium), 81591 -81 -3 (Trimesium)), 1-methyl-3- difluoromethyl-1 H-pyrazole-4-carboxylic acid (2-dichloromethylene-3-ethyl-1 -methyl-indan-4- yl)-amide (1072957-71 -1 ), 1-methyl-3-difluoromethyl-1 H-pyrazole-4-carboxylic acid (4'- methylsulfanyl-biphenyl-2-yl)-amide, 1 -methyl-3-difluoromethyl-4H-pyrazole-4-carboxylic acid [2-(2,4-dichloro-phenyl)-2-methoxy-1-methyl-ethyl]-amide, (5-Chloro-2,4-dimethyl-pyridin-3- yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, (5-Bromo-4-chloro-2-methoxy-pyridin-3- yl)-(2,3,4-trimethoxy-6-methyl-phenyl)-methanone, 2-{2-[(E)-3-(2,6-Dichloro-phenyl)-1- methyl-prop-2-en-(E)-ylideneaminooxymethyl]-phenyl}-2-[(Z)-methoxyimino]-N-methyl- acetamide, 3-[5-(4-Chloro-phenyl)-2,3-dimethyl-isoxazolidin-3-yl]-pyridine.

Another aspect of invention is related to the use of a compound of formula I or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal mixture comprising at least one compound of formula I or at least one preferred individual compound as above-defined, in admixture with other fungicides, as described above, for controlling or preventing infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non-living materials by phytopathogenic microorganisms, preferably fungal organisms.

A further aspect of invention is related to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of non-living materials by

phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula I or of a preferred individual compound as above-defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the non-living materials.

Controlling or preventing means reducing infestation by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, to such a level that an improvement is demonstrated.

A preferred method of controlling or preventing an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, which comprises the application of a compound of formula I, or an agrochemical composition which contains at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen. However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). In crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.

A formulation, e.g. a composition containing the compound of formula I, and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example solvents, solid carriers and, optionally, surface active compounds (surfactants).

The agrochemical formulations and/or compositions will usually contain from 0.1 to 99% by weight, preferably from 0.1 to 95% by weight, of the compound of formula I, 99.9 to 1 % by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from 0 to 25% by weight, preferably from 0.1 to 25% by weight, of a surfactant.

Advantageous rates of application are normally from 5g to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1 kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as seed drenching agent, convenient dosages are from 10mg to 1 g of active substance per kg of seeds.

Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.

The following non-limiting example illustrates the above-described invention in more detail.

Example 1 : This example illustrates the preparation of acetaldehyde 0-[3-(2-{1-[2-(3,5-bis- difluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)-5-(2-fluoro-phenyl)-4,5- dihydro-isoxazol-5-ylmethyl]-oxime (compound l.b.109) a) Preparation of 1 -(1 -bromomethyl-vinyl)-2-fluoro-benzene

N-Bromosuccinimide (12.8 g, 73 mmol) is added to a solution of 1 -fluoro-2- isopropenyl-benzene (9.9 g, 73 mmol) in 16 ml of tetrachloromethane. The mixture is heated to reflux for 48 h, then cooled to room temperature and filtered. The filtrate is concentrated under reduced pressure, the residue is purified by column chromatography on silica gel (cyclohexane / ethyl acetate 5 : 1 ) to give 1-(1-bromomethyl-vinyl)-2-fluoro-benzene as a colourless oil. ¹H-NMR (400 MHz, CDCI₃): δ = 4.39 (s, 2H), 5.42 (s, 1 H), 5.61 (s, 1 H), 7.08 (t, 1 H), 7.17 (t, 1 H), 7.29 - 7.37 (m, 2H). MS: m/z = 216 (M+1 ). b) Preparation of acetaldehyde 0-[2-(2-fluoro-phenyl)-allyl]-oxime

Sodium hydride (0.4 g, 10 mmol) was added in portions at 0 °C to a solution of acetaldehyde oxime (0.55 g, 9.3 mmol) in 16 ml of Ν,Ν-dimethylformamide. After the addition is complete, the reaction mixture is brought to room temperature, stirred for 30 mins and then cooled again to 0 °C. A solution of 1-(1 -bromomethyl-vinyl)-2-fluoro-benzene (2.9 g, 10 mmol) in 10 ml of Ν,Ν-dimethylformamide is added slowly and the reaction mixture is warmed again to room temperature, stirred for 3 h, poured on water and extracted with ethyl acetate. The combined organic layer is washed with water and brine, dried over sodium sulphate and concentrated under reduced pressure. The remainder is purified by

chromatography on silica gel (cyclohexane / ethyl acetate 9 : 1 ) to give acetaldehyde 0-[2-(2- fluoro-phenyl)-allyl]-oxime as a colourless oil. ¹H-NMR (400 MHz, CDCI₃): δ = 1.75 (d, 3H), 4.93 (s, 2H), 5.49 (d, 2H), 6.76 (q, 1 H), 7.02 - 7.13 (m, 2H), 7.22 - 7.34 (m, 2H). MS: m/z = 194 (M+1 ). c) Preparation of 4-{4-[5-eth-(E)-ylideneaminooxymethyl-5-(2-fluoro-phenyl)-4,5-dihydro- isoxazol-3-yl]-thiazol-2-yl}-piperidine-1 -carboxylic acid tert-butyl ester

A suspension of 4-[4-(hydroxyimino-methyl)-thiazol-2-yl]-piperidine-1 -carboxylic acid tert-butyl ester (0.47 g, 1.5 mmol) in 30 ml of methanol is added dropwise to a solution of acetaldehyde 0-[2-(2-fluoro-phenyl)-allyl]-oxime (0.46 g, 2.4 mmol), (diacetoxy)iodobenzene (0.53 g, 1.6 mmol) and trifluoroacetic acid (43 mg, 0.37 mmol) in 15 ml of methanol. The reaction mixture is stirred for 6 h at room temperature, then concentrated under reduced pressure. The remainder is purified by chromatography on silica gel (cyclohexane / ethyl acetate 6 : 1 ) to give 4-{4-[5-eth-(E)-ylideneaminooxymethyl-5-(2-fluoro-phenyl)-4,5-dihydro- isoxazol-3-yl]-thiazol-2-yl}-piperidine-1 -carboxylic acid tert-butyl ester. ¹H-NMR (400 MHz, CDCI₃): δ = 1.47 (s, 9H), 1.71 (dd, 2H), 1.75 (d, 2H), 2.09 (dd, 2H), 2.86 (t, 2H), 3.17 (dt, 1 H), 3.56 (dd, 1 H), 3.99 (dd, 1 H), 4.13 - 4.22 (m, 2H), 4.53 (dd, 2H), 6.68 (q, 1 H), 7.07 (t, 1 H), 7.18 (t, 1 H), 7.28 - 7.32 (m, 1 H), 7.57 (s, 1 H), 7.75 (t, 1 H). MS: m/z = 503 (M+1 ). d) Preparation of acetaldehyde 0-[5-(2-fluoro-phenyl)-3-(2-piperidin-4-yl-thiazol-4-yl)- 4,5-dihydro-isoxazol-5-ylmethyl]-oxime

2.9 ml of a 1 .25 M solution of hydrochloric acid in ethanol are added to a solution of 4- {4-[5-eth-(E)-ylideneaminooxymethyl-5-(2-fluoro-phenyl)-4,5-dihydro-isoxazol-3-yl]-thiazol-2- yl}-piperidine-1 -carboxylic acid tert-butyl ester (0.18 g, 0.36 mmol) in 3 ml of a 1 : 1 mixture of methanol and dichloromethane. The reaction mixture was stirred 16 h at room temperature, then concentrated under reduced pressure. The remainder was dried in high vacuum to deliver acetaldehyde 0-[5-(2-fluoro-phenyl)-3-(2-piperidin-4-yl-thiazol-4-yl)- 4,5-dihydro-isoxazol-5-ylmethyl]-oxime as a white foam. ¹H-NMR (400 MHz, CDCI₃): δ = 1 .70 - 1.77 (m, 4H), 2.12 (dd, 2H), 2.91 (t, 2H), 3.14 (dt, 1 H), 3.53 (dd, 1 H), 4.01 (dd, 1 H), 4.15 - 4.23 (m, 2H), 4.54 (dd, 2H), 6.70 (q, 1 H), 7.08 (t, 1 H), 7.19 (t, 1 H), 7.26 - 7.33 (m, 1 H), 7.56 (s, 1 H), 7.72 (t, 1 H). MS: m/z = 440 (M+1 ). e) Preparation of acetaldehyde 0-[3-(2-{1 -[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]- piperidin-4-yl}-thiazol-4-yl)-5-(2-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-oxime (compound l.b.109)

Acetaldehyde 0-[5-(2-fluoro-phenyl)-3-(2-piperidin-4-yl-thiazol-4-yl)-4,5-dihydro- isoxazol-5-ylmethyl]-oxime (0.15 g, 0.34 mmol) is dissolved in 3 ml of N,N- dimethylformamide and the mixture is cooled to 0 °C. Diisoproplyethylamine (0.11 g, 0.86 mmol) is added and the reaction mixture is stirred for 10 min at 0 °C. (3,5-Bis-difluoromethyl- pyrazol-1-yl)-acetic acid (78 mg, 0.34 mmol) and (benzotriazol-l -yloxy)tris(dimethylamino) phosphonium hexafluorophosphate (BOP, Castro's reagent, 0.15 g, 0.34 mmol) are added, then the reaction mixture is stirred for further 10 min at 0 °C and 16 h at room temperature. Subsequently the reaction mixture is poured on water, and extracted with ethyl acetate. The organic layer is washed with saturated aqueous sodium hydrogencarbonate solution and brine, dried over sodium sulphate and concentrated under reduced pressure. The remainder is purified by chromatography on silica gel (cyclohexane / ethyl acetate 6 : 1 ) to give acetaldehyde 0-[3-(2-{1-[2-(3,5-bis-difluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol- 4-yl)-5-(2-fluoro-phenyl)-4,5-dihydro-isoxazol-5-ylmethyl]-oxime (Compound 1.b.109) as a white foam. ¹H-NMR (400 MHz, CDCI₃): δ = 1 .72 - 1 .89 (m, 5H), 2.21 (d, 1 H), 2.29 (d, 1 H), 2.93 (t, 1 H), 3.35 (t, 2H), 3.61 (dd, 1 H), 3.94 (d, 1 H), 4.03 (d, 1 H), 4.42 - 4.60 (m, 3H), 5.20 (s, 2H), 6.72 (dd, 1 H), 6.80 (t, 1 H), 6.87 (d, 1 H), 7.1 1 (t, 1 H), 7.20 (t, 1 H), 7.32 (dd, 1 H), 7.62 (s, 1 H), 7.79 (t, 1 H). MS: m/z = 611 (M+1 ).

Table 1 below illustrates examples of individual compounds of formula I according to the invention.

Table 1 : individual compounds of formula I according to the invention

Comp. R R T Y G Y _R10 R R

No.

001 F₃C H₃C CH N S CH H H CH₃

002 F₃C H₃C CH N S CH H CH₃ CH₃

003 F₃C H₃C CH N s CH H H CF₃

004 F₃C H₃C CH N s CH H H CH₂CH₃

005 F₃C H₃C CH N s CH H CH₃ cyclopropyl

006 F₃C H₃C CH N s CH CH₃ H CH₃

007 F₃C H₃C CH N s N H H CH₃

008 F₃C H₃C CH N s N H CH₃ CH₃

009 F₃C H₃C CH N s N H H CF₃

010 F₃C H₃C CH N s N H H CH₂CH₃

01 1 F₃C H₃C CH N s N H CH₃ cyclopropyl

012 F₃C H₃C CH N s N CH₃ H CH₃

013 F₃C H₃C CH N 0 CH H H CH₃

014 F₃C H₃C CH N 0 CH H CH₃ CH₃

015 F₃C H₃C CH N 0 CH H H CF₃

016 F₃C H₃C CH N 0 CH H H CH₂CH₃

017 F₃C H₃C CH N 0 CH H CH₃ cyclopropyl

018 F₃C H₃C CH N 0 CH CH₃ H CH₃

019 F₃C H₃C N N s CH H H CH₃

020 F₃C H₃C N N s CH H CH₃ CH₃

021 F₃C H₃C N N s CH H H CF₃

022 F₃C H₃C N N s CH H H CH₂CH₃

023 F₃C H₃C N N s CH H CH₃ cyclopropyl F₃C H₃C N N S CH CH₃ H CH₃

F₃C H₃C N N S N H H CH₃

F₃C H₃C N N s N H CH₃ CH₃

F₃C H₃C N N s N H H CF₃

F₃C H₃C N N s N H H CH₂CH₃

F₃C H₃C N N s N H CH₃ cyclopropyl

F₃C H₃C N N s N CH₃ H CH₃

F₃C H₃C N N 0 CH H H CH₃

F₃C H₃C N N 0 CH H CH₃ CH₃

F₃C H₃C N N 0 CH H H CF₃

F₃C H₃C N N 0 CH H H CH₂CH₃

F₃C H₃C N N 0 CH H CH₃ cyclopropyl

F₃C H₃C N N 0 CH CH₃ H CH₃

H₃C H₃C CH N s CH H H CH₃

H₃C H₃C CH N s CH H CH₃ CH₃

H₃C H₃C CH N s CH H H CF₃

H₃C H₃C CH N s CH H H CH₂CH₃

H₃C H₃C CH N s CH H CH₃ cyclopropyl

H₃C H₃C CH N s CH CH₃ H CH₃

H₃C H₃C CH N s N H H CH₃

H₃C H₃C CH N s N H CH₃ CH₃

H₃C H₃C CH N s N H H CF₃

H₃C H₃C CH N s N H H CH₂CH₃

H₃C H₃C CH N s N H CH₃ cyclopropyl

H₃C H₃C CH N s N CH₃ H CH₃

H₃C H₃C CH N 0 CH H H CH₃

H₃C H₃C CH N 0 CH H CH₃ CH₃

H₃C H₃C CH N 0 CH H H CF₃

H₃C H₃C CH N 0 CH H H CH₂CH₃

H₃C H₃C CH N 0 CH H CH₃ cyclopropyl

H₃C H₃C CH N 0 CH CH₃ H CH₃

H₃C H₃C N N s CH H H CH₃

H₃C H₃C N N s CH H CH₃ CH₃

H₃C H₃C N N s CH H H CF₃

H₃C H₃C N N s CH H H CH₂CH₃

H₃C H₃C N N s CH H CH₃ cyclopropyl

H₃C H₃C N N s CH CH₃ H CH₃ H₃C H₃C N N S N H H CH₃

H₃C H₃C N N S N H CH₃ CH₃

H₃C H₃C N N s N H H CF₃

H₃C H₃C N N s N H H CH₂CH₃

H₃C H₃C N N s N H CH₃ cyclopropyl

H₃C H₃C N N s N CH₃ H CH₃

H₃C H₃C N N 0 CH H H CH₃

H₃C H₃C N N 0 CH H CH₃ CH₃

H₃C H₃C N N 0 CH H H CF₃

H₃C H₃C N N 0 CH H H CH₂CH₃

H₃C H₃C N N 0 CH H CH₃ cyclopropyl

H₃C H₃C N N 0 CH CH₃ H CH₃

F₂HC H₃C CH N s CH H H CH₃

F₂HC H₃C CH N s CH H CH₃ CH₃

F₂HC H₃C CH N s CH H H CF₃

F₂HC H₃C CH N s CH H H CH₂CH₃

F₂HC H₃C CH N s CH H CH₃ cyclopropyl

F₂HC H₃C CH N s CH CH₃ H CH₃

F₂HC H₃C CH N s N H H CH₃

F₂HC H₃C CH N s N H CH₃ CH₃

F₂HC H₃C CH N s N H H CF₃

F₂HC H₃C CH N s N H H CH₂CH₃

F₂HC H₃C CH N s N H CH₃ cyclopropyl

F₂HC H₃C CH N s N CH₃ H CH₃

F₂HC H₃C CH N 0 CH H H CH₃

F₂HC H₃C CH N 0 CH H CH₃ CH₃

F₂HC H₃C CH N 0 CH H H CF₃

F₂HC H₃C CH N 0 CH H H CH₂CH₃

F₂HC H₃C CH N 0 CH H CH₃ cyclopropyl

F₂HC H₃C CH N 0 CH CH₃ H CH₃

F₂HC H₃C N N s CH H H CH₃

F₂HC H₃C N N s CH H CH₃ CH₃

F₂HC H₃C N N s CH H H CF₃

F₂HC H₃C N N s CH H H CH₂CH₃

F₂HC H₃C N N s CH H CH₃ cyclopropyl

F₂HC H₃C N N s CH CH₃ H CH₃

F₂HC H₃C N N s N H H CH₃ 098 F₂HC H₃C N N S N H CH₃ CH₃

099 F₂HC H₃C N N S N H H CF₃

100 F₂HC H₃C N N s N H H CH₂CH₃

101 F₂HC H₃C N N s N H CH₃ cyclopropyl

102 F₂HC H₃C N N s N CH₃ H CH₃

103 F₂HC H₃C N N 0 CH H H CH₃

104 F₂HC H₃C N N 0 CH H CH₃ CH₃

105 F₂HC H₃C N N 0 CH H H CF₃

106 F₂HC H₃C N N 0 CH H H CH₂CH₃

107 F₂HC H₃C N N 0 CH H CH₃ cyclopropyl

108 F₂HC H₃C N N 0 CH CH₃ H CH₃

109 F₂HC F₂HC CH N s CH H H CH₃

110 F₂HC F₂HC CH N s CH H CH₃ CH₃

11 1 F₂HC F₂HC CH N s CH H H CF₃

112 F₂HC F₂HC CH N s CH H H CH₂CH₃

113 F₂HC F₂HC CH N s CH H CH₃ cyclopropyl

114 F₂HC F₂HC CH N s CH CH₃ H CH₃

115 F₂HC F₂HC CH N s N H H CH₃

116 F₂HC F₂HC CH N s N H CH₃ CH₃

117 F₂HC F₂HC CH N s N H H CF₃

118 F₂HC F₂HC CH N s N H H CH₂CH₃

119 F₂HC F₂HC CH N s N H CH₃ cyclopropyl

120 F₂HC F₂HC CH N s N CH₃ H CH₃

121 F₂HC F₂HC CH N 0 CH H H CH₃

122 F₂HC F₂HC CH N 0 CH H CH₃ CH₃

123 F₂HC F₂HC CH N 0 CH H H CF₃

124 F₂HC F₂HC CH N 0 CH H H CH₂CH₃

125 F₂HC F₂HC CH N 0 CH H CH₃ cyclopropyl

126 F₂HC F₂HC CH N 0 CH CH₃ H CH₃

127 F₂HC F₂HC N N s CH H H CH₃

128 F₂HC F₂HC N N s CH H CH₃ CH₃

129 F₂HC F₂HC N N s CH H H CF₃

130 F₂HC F₂HC N N s CH H H CH₂CH₃

131 F₂HC F₂HC N N s CH H CH₃ cyclopropyl

132 F₂HC F₂HC N N s CH CH₃ H CH₃

133 F₂HC F₂HC N N s N H H CH₃

134 F₂HC F₂HC N N s N H CH₃ CH₃ 135 F₂HC F₂HC N N S N H H CF₃

136 F₂HC F₂HC N N S N H H CH₂CH₃

137 F₂HC F₂HC N N s N H CH₃ cyclopropyl

138 F₂HC F₂HC N N s N CH₃ H CH₃

139 F₂HC F₂HC N N 0 CH H H CH₃

140 F₂HC F₂HC N N 0 CH H CH₃ CH₃

141 F₂HC F₂HC N N 0 CH H H CF₃

142 F₂HC F₂HC N N 0 CH H H CH₂CH₃

143 F₂HC F₂HC N N 0 CH H CH₃ cyclopropyl

144 F₂HC F₂HC N N 0 CH CH₃ H CH₃

145 F₃C F₃C CH N s CH H H CH₃

146 F₃C F₃C CH N s CH H CH₃ CH₃

147 F₃C F₃C CH N s CH H H CF₃

148 F₃C F₃C CH N s CH H H CH₂CH₃

149 F₃C F₃C CH N s CH H CH₃ cyclopropyl

150 F₃C F₃C CH N s CH CH₃ H CH₃

151 F₃C F₃C CH N s N H H CH₃

152 F₃C F₃C CH N s N H CH₃ CH₃

153 F₃C F₃C CH N s N H H CF₃

154 F₃C F₃C CH N s N H H CH₂CH₃

155 F₃C F₃C CH N s N H CH₃ cyclopropyl

156 F₃C F₃C CH N s N CH₃ H CH₃

157 F₃C F₃C CH N 0 CH H H CH₃

158 F₃C F₃C CH N 0 CH H CH₃ CH₃

159 F₃C F₃C CH N 0 CH H H CF₃

160 F₃C F₃C CH N 0 CH H H CH₂CH₃

161 F₃C F₃C CH N 0 CH H CH₃ cyclopropyl

162 F₃C F₃C CH N 0 CH CH₃ H CH₃

163 F₃C F₃C N N s CH H H CH₃

164 F₃C F₃C N N s CH H CH₃ CH₃

165 F₃C F₃C N N s CH H H CF₃

166 F₃C F₃C N N s CH H H CH₂CH₃

167 F₃C F₃C N N s CH H CH₃ cyclopropyl

168 F₃C F₃C N N s CH CH₃ H CH₃

169 F₃C F₃C N N s N H H CH₃

170 F₃C F₃C N N s N H CH₃ CH₃

171 F₃C F₃C N N s CH H H CF₃ 172 F₃C F₃C N N S CH H H CH₂CH₃

173 F₃C F₃C N N S CH H CH₃ cyclopropyl

174 F₃C F₃C N N s CH CH₃ H CH₃

175 F₃C F₃C N N 0 CH H H CH₃

176 F₃C F₃C N N 0 CH H CH₃ CH₃

177 F₃C F₃C N N 0 CH H H CF₃

178 F₃C F₃C N N 0 CH H H CH₂CH₃

179 F₃C F₃C N N 0 CH H CH₃ cyclopropyl

180 F₃C F₃C N N 0 CH CH₃ H CH₃

where

a) 180 compounds of formula

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1.

b) 180 compounds of formula (l.b):

c) 180 compounds of formula (l.c):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. d) 180 compounds of formula

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y are as defined in Table 1. e) 180 compounds of formula (l.e):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1 f) 180 compounds of formula (l.f):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. h 180 compounds of formula l.h):

wherein R', R", R^IU, R", R^IJ, Q> T, Y' and Y are as defined in Table 1.

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. j) 180 compounds of formula (l.j):

k 180 compounds of formula (I. k):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1.

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. n) 180 compounds of formula (l.n):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. o) 180 compounds of formula (I. o):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. p) 180 compounds of formula (I. p):

180 compounds of formula (I. q):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. s) 180 compounds of formula (I .s):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. t 180 compounds of formula (l.t):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. u) 180 compounds of formula (I. u):

v) 180 compounds of formula (l.v):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and are as defined in Table 1. w 1 compounds of formula (l.w):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and are as defined in Table 1.

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. y) 180 compounds of formula (I. y):

z) 180 compounds of formula (I. z):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. aa) 180 compounds of formula (l.aa):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1 ab) 180 compounds of formula (l.ab):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. ac) 180 compounds of formula (l.ac):

wherein R , R , R^1U, R¹², R¹³, G , T, Y and Y² are as defined in Table 1. ad) 180 compounds of formula (I. ad):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. ae) 180 compounds of formula (l.ae):

wherein R , R", R^1U, R , R^1J, G , - Tr, Y and are as defined in Table 1.

wherein R , R² R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. aj) 180 compounds of formula (l.aj):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. ak 180 compounds of formula (l.ak):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. al) 180 compounds of formula (l.al):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. am) 180 compounds of formula (I. am):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. an) 180 compounds of formula (I. an):

wherein R¹, R², R ⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1 ao) 180 compounds of formula (l.ao):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. ap) 180 compounds of formula (Lap):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1 ar) 180 compounds of formula (l.ar):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. as) 180 compounds of formula (I. as):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. at 180 compounds of formula (I. at):

wherein R¹, R², R¹⁰, R¹², R¹³, G², T, Y¹ and Y² are as defined in Table 1. au) 180 compounds of formula (l.au):

av) 180 compounds of formula (l.av):

aw 180 compounds of formula (Law):

wherein ¹ _, R² R¹⁰ ' ¹²■ R ^R13 - _r ^G ₂. ^T' ^Y and Y are as defined in Table 1.

Throughout this description, temperatures are given in degrees Celsius and "m.p." means melting point. LC/MS means Liquid Chromatography Mass Spectroscopy and the description of the apparatus and the method is:

Spectra were recorded on a Mass Spectrometer from Waters equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30- 60 V, Extractor: 2.00 V, Source Temperature: 150°C, Desolvation Temperature: 350°C, Cone Gas Flow: 0 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3 , 1.8 μιη, 30 x 2.1 mm, Temp: 60 °C, DAD

Wavelength range (nm): 210 to 500, Solvent Gradient: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH: gradient: gradient: 0 min 0% B, 100%A; 1.2- 1.5min 100% B; Flow (ml/min) 0.85

Table 2: Melting point and LC/MS data for compounds of Table 1 Compound No. Melting point (°C) LC/MS

I.a.001 t = 1.75 min; MS: m/z 575 [M+1]⁺ l.a.002 Rt = 1.83 min; MS: m/z 589 [M+1]⁺ l.a.005 Rt = 1.95 min; MS: m/z 615 [M+1f l.a.109 Rt = 1.72 min; MS: m/z 593 [M+1f l.a.110 Rt = 1.80 min; MS: m/z 607 [M+1f l.a.113 Rt = 1.92 min; MS: m/z 633 [M+1]⁺ l.d.001 Rt = 1.80 min; MS: m/z 593 [M+1]⁺ l.d.002 Rt = 1.84 min; MS: m/z 607 [M+1]⁺ ld.005 Rt = 1.96 min; MS: m/z 633 [M+1]⁺ l.d.109 Rt = 1.76 min; MS: m/z 611 [M+1]⁺ l.d.110 Rt = 1.81 min; MS: m/z 625 [M+1]⁺ l.d.113 Rt = 1.92 min; MS: m/z 651 [M+1f l.b.109 Rt = 1.76 min; MS: m/z 61 1 [M+1f

The compounds according to the present invention can be prepared according to the above-mentioned reaction schemes, in which, unless otherwise stated, the definition of each variable is as defined above for a compound of formula (I).

Biological examples

Phytophthora infestans I tomato / leaf disc preventative (tomato late blight)

Tomato leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 - 7 days after application).

Compounds l.a.001 , l.a.002, l.a.005, l.a.109, l.a.1 10, l.a.113, l.d.001 , l.d.002, l.d.005, l.d.109, l.d.1 10, l.d.1 13 and l.b.109 at 200 ppm gives at least 80% disease control in this test when compared to untreated control plants under the same conditions, which show extensive disease development.

Phytophthora infestans I potato / preventative (potato late blight)

2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 2 days after application. The inoculated test plants are incubated at 18° C with 1 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (5 - 7 days after application).

Compounds l.a.001 , l.a.002, l.a.005, l.a.109, l.a.1 10, l.a.1 13, l.d.001 , l.d.002, l.d.005, l.d.109, l.d.1 10, l.d.1 13 and l.b.109 at 200 ppm gives at least 80% disease control in this test when compared to untreated control plants under the same conditions, which show extensive disease development.

Phytophthora infestans I potato / curative (potato late blight)

2-week old potato plants cv. Bintje are inoculated by spraying them with a sporangia suspension one day before application. The inoculated plants are sprayed in a spray chamber with the formulated test compound diluted in water. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (3 - 4 days after application).

Compounds l.a.001 , l.a.002, l.a.005, l.a.109, l.a.1 10, l.a.113, l.d.001 , l.d.002, l.d.005, l.d.109, l.d.1 10, l.d.113 and l.b.109 at 200 ppm gives at least 80% disease control in this test when compared to untreated control plants under the same conditions, which show extensive disease development.

Phytophthora infestans I potato / long lasting (potato late blight)

2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 6 days after application. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (9 - 1 1 days after application).

Plasmopara viticola I grape / leaf disc preventative (grape downy mildew) Grape vine leaf disks are placed on water agar in multiwell plates (24-well format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are incubated at 19°C and 80% rh under a light regime of 12 h light / 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 - 8 days after application).

Plasmopara viticola I grape / preventative (grape downy mildew)

5-week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants plants are inoculated by spraying a sporangia suspension on their lower leaf surface one day after application. The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (6 - 8 days after application).

Plasmopara viticola I grape / curative (grape downy mildew)

5-week-old grape seedlings cv. Gutedel are inoculated by spraying a sporangia suspension on their lower leaf surface one day before application. The inoculated grape plants are sprayed in a spray chamber with the formulated test compound diluted in water. The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (4 - 6 days after application). Compounds l.a.001 , l.a.109, l.d.001 , l.d.109 and l.b.109 at 200 ppm gives at least

80% disease control in this test when compared to untreated control plants under the same conditions, which show extensive disease development. Plasmopara viticola I grape / long lasting (grape downy mildew)

5-week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying a sporangia suspension on their lower leaf surface 6 days after application. The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (1 1 - 13 days after application).

Compounds l.a.001 , l.a.002, l.a.109, l.a.110, l.d.001 , l.d.002, l.d.109, l.d.1 10 and I .b.109 at 200 ppm gives at least 80% disease control in this test when compared to untreated control plants under the same conditions, which show extensive disease development.

Claims

What is claimed is:

G¹ and G² are independently O or S;

T is CR¹⁴ or N;

Y¹ and Y² are independently CR¹⁵ or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, halogen, cyano, C C₄alkyl, Ci-

C₄alkoxy, Ci-C₄haloalkyl, C₃-C₅cycloalkyl or d-C₄alkylthio;

R⁹ is aryl or heteroaryl, both optionally substituted by one or more R¹⁶;

R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen, cyano, CrC₄alkyl, Ci-

C₄haloalkyl, C₃-C₅cycloalkyl, aryl or heteroaryl, the aryl or heteroaryl optionally substituted by one or more R¹⁶; or

R¹⁰ and R¹ together with the carbon atom to which they are attached, independently form a saturated or partially unsaturated three- to five-membered alicyclic ring, optionally substituted by halogen, cyano, CrC₄alkyl, Ci-C alkoxy or CrC₄haloalkyl;

R¹³ is CrC alkyl, Ci-C haloalkyl, C₃-C₅cycloalkyl, Ci-C alkylcarbonyl, aryl, heteroaryl, the aryl or heteroaryl optionally substituted by one or more R¹⁶;

R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

R¹⁶ is halogen, cyano, hydroxyl, amino, formyl, CrC₄alkyl, Ci-C haloalkyl, C₃-C₅cycloalkyl, C₂-C₅alkenyl, C₂-C₅haloalkenyl, C₂-C₅alkynyl, C₂-C₅haloalkynyl, Ci-C₄alkoxy, Cr

C₄haloalkoxy, C₃-C₅cycloalkoxy, C₃-C₅alkenyloxy, C₃-C₅haloalkenyloxy, C₃-C₅alkynyloxy, C₃- C₅haloalkynyloxy, Ci-C alkylamino, Ci-C dialkylamino, CrC alkylcarbonyl, C

C₄haloalkylcarbonyl, C₃-C₅cycloalkylcarbonyl, Ci-C₄alkylcarbonyl 0-Ci-C₄alkyloxime, C C₄haloalkylcarbonyl 0-C C alkyloxime, C₃-C₅cycloalkylcarbonyl 0-C C₄alkyloxime, C C₄alkylcarbonyloxy, CrC₄haloalkylcarbonyloxy, C₃-C₅cycloalkylcarbonyloxy, C

C₄alkoxycarbonyl, CrC₄haloalkoxycarbonyl, C₃-C₅cycloalkoxycarbonyl, aryl, heteroaryl, arylCi-C alkyl or heteroarylCi-C₄alkyl; or a salt or a N-oxide thereof.

2. A compound according to claim 1 wherein R⁹ is phenyl which is optionally substituted by one or more R¹⁶.

3. A compound according to claim 1 wherein R⁹ is phenyl, which is substituted by hydrogen, halogen, cyano, Ci-C₄alkyl, Ci-C₄haloalkyl or C₃-C₅alkynyloxy.

4. A compound according to claim 1 wherein R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen, Ci-C₄alkyl, CrC₄haloalkyl or C₃-C₅cycloalkyl.

5. A compound according to claim 1 wherein:

G¹ is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are methyl or halomethyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, halogen, cyano, CrC alkyl, d-

C₄alkoxy, Ci-C₄haloalkyl, C₃-C₅cycloalkyl or CrC₄alkylthio;

R⁹ is aryl or heteroaryl, both optionally substituted by one or more R¹⁶;

C₄haloalkyl, C₃-C₅cycloalkyl, aryl or heteroaryl; or

R¹⁰ and R¹¹ together with the carbon atom to which they are attached, independently form a saturated or partially unsaturated three- to five-membered alicyclic ring, optionally substituted by halogen, cyano, CrC alkyl, Ci-C₄alkoxy or Ci-C haloalkyl;

R¹³ is CrC₄alkyl, Ci-C₄haloalkyl, C₃-C₅cycloalkyl, Ci-C₄alkylcarbonyl, aryl, heteroaryl, the aryl or heteroaryl optionally substituted by one or more R¹⁶;

R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

or a salt or a N-oxide thereof.

6. A compound according to claim 1 wherein:

G¹ is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N; n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are methyl or halomethyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, halogen, methyl, halomethyl or methylthio;

R⁹ is phenyl which is optionally substituted by one or more R¹⁵;

R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

or a salt or a N-oxide thereof.

7. A compound according to claim 1 wherein:

G¹ is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ;

R¹ and R² each independently are methyl or halomethyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen or methyl;

R⁹ is phenyl, which is substituted by hydrogen, halogen, cyano, Ci-C₄alkyl, CrC₄haloalkyl or C₃-C₅alkynyloxy.

R¹⁰, R¹¹ and R¹² each independently are hydrogen, halogen or Ci-C₄alkyl;

R¹³ is C C₄alkyl or C₃-C₅cycloalkyl;

R¹⁴ is hydrogen, halogen or hydroxyl;

R¹⁵ is hydrogen, halogen or cyano;

or a salt or a N-oxide thereof.

8. A compound according to claim 1 wherein:

G¹ is O

G² is S;

T is CH or N;

Y¹ and Y² are independently CH or N;

n is 1 or 2;

p is 1 or 2, providing that when n is 2, p is 1 ; R¹ and R² each independently are methyl, difluoromethyl or trifluoromethyl;

R³, R⁴, R⁵, R⁶, R⁷ and R⁸ are hydrogen;

R⁹ is phenyl, which is substituted by hydrogen, halogen or C₃-C₅alkynyloxy.

R¹⁰, R¹¹ and R¹² each independently are hydrogen or CrC₄alkyl;

5 R¹³ is CrC₄alkyl or C₃-C₅cycloalkyl;

R¹⁴ is hydrogen or hydroxyl;

R¹⁵ is hydrogen or cyano;

or a salt or a N-oxide thereof.

10 9. A compound according to any one of claims 1 to 8, wherein G¹, is O, G² is S, T is CH, Y¹ is N, and Y² is CH.

10. A compound according to any one of claims 1 to 9, wherein p is 1 and n is 2.

15 1 1. A compound according to any one of the claims 1 to 10, wherein R¹ and R² each independently are methyl, difluoromethyl or trifluoromethyl and R³, R⁴, R⁵, R⁶, R⁷ and R⁸ each independently are hydrogen, or methyl.

12. A compound according to anyone of claims 1 to 1 1 , wherein R³, R⁴, R⁵, R⁶, R⁷ and R⁸ 20 are hydrogen.

13. A

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y² , n and p are as defined in 25 anyone of claims 1 to 12 for a compound of formula I, and salts and N-oxides thereof,

or a c

wherein R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², R¹³, G², T, Y¹, Y² , n and p are as defined in anyone of claims 1 to 12 for a compound of formula I and E is a protecting group, such as C1-C4 alkylcarbonyl, benzyl or C1-C4 alkoxycarbonyl, in particular acetyl, benzyl or tert- butoxycarbonyl, and salts and N-oxides thereof.

14. A composition comprising at least one compound as defined in any one of claims 1 to 12 and an agriculturally acceptable carrier, optionally comprising an adjuvant, and optionally comprising one or more additional pesticidally active compounds.

15. A method of controlling or preventing an infestation of plants, propagation material thereof, harvested crops or of non-living materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, which comprises the application of a compound as defined in any one of claims 1 to 12, to the plant, to parts of the plants or to the locus thereof, to propagation material thereof or to any part of the non-living materials.