Herbicidal benzoxazines

Abstract

Disclosed are compounds of formula (I), including all stereoisomers, N-oxides and salts thereof, agricultural compositions containing them and their use as herbicides, A is a 5-or 6-membered heterocyclic ring containing a ring member selected from the group consisting of carbon atoms and up to 4 heteroatoms independently selected from the group consisting of up to 2 O, up to 2 S and up to 4 N atoms, one or two carbon or sulfur ring members of the heterocyclic ring may optionally be in the oxidized form of carbonyl, sulfonyl, sulfinyl moieties, said ring being bound to the remainder of Formula 1 via a carbon atom or heteroatom and optionally substituted by 1 to 4 R1; and R1a, R1b, R2, R3a, R3b, R4a, R4b, X1, X2, n, p and q are as defined in the disclosure. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to certain benzoxazine herbicides, N-oxides, salts and compositions thereof, and methods of using the same for controlling undesirable vegetation. Background Art

[0002] Controlling undesirable vegetation is extremely important in realizing high crop efficiency.Realizing the selective control of weed growth, especially in such useful crops, especially such as rice, soybean, beet, corn, potato, wheat, barley, tomato and plantation crops, is highly desirable.The uninhibited weed growth in such useful crops can cause a significant decline in output, and thus cause the cost increase of the consumer.Controlling undesirable vegetation in non-crop areas is also important.For these purposes, many products are commercially available, but continue to need more effective, lower cost, lower toxicity, safer to the environment or novel compounds with different action sites. Summary of the invention

[0003] The present invention relates to compounds of formula 1, all stereoisomers, N-oxides and salts thereof, agricultural compositions containing them, and their use as herbicides:

[0004]

[0005] in

[0006] A is a 5- or 6-membered heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, one or two carbon or sulfur ring members of the heterocyclic ring may be optionally in the oxidized form of a carbonyl, thiocarbonyl, sulfonyl, sulfinyl moiety, the ring being bonded to the remainder of Formula 1 via a carbon atom or heteroatom and optionally substituted by 1 to 4 R 1 replace;

[0007] R 1 Independently R 1a , (R 1b ) m , R 1c or any combination thereof;

[0008] R 1ais H, halogen, cyano, nitro, amino, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C3–C7 alkyloxacycloalkyl, C2–C6 thiacycloalkyl, C3–C7 thiacycloalkylalkyl, C3–C7 alkylthiacycloalkyl, C2–C6 (O-thia)cycloalkyl, C3–C7 (O-thia)cycloalkylalkyl, C3–C7 alkyl(O-thia)cycloalkyl, C2–C6(O2thia)cycloalkyl, C3–C7(O2thia)cycloalkylalkyl, C3–C7 alkyl(O2thia)cycloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C1–C7 haloalkoxy, C1–C7 alkylthio, C2–C7 alkylthioalkyl, C1–C5 alkylsulfinyl, C1–C5 alkylsulfonyl, C1–C4 alkyl Sulfonate, C1–C5 haloalkylthio, C1–C5 haloalkylsulfinyl, C1–C5 haloalkylsulfonyl, C2–C7 alkylsulfinylalkyl, C2–C7 alkylsulfonylalkyl, C2–C7 haloalkylthioalkyl, C2–C7 haloalkylsulfinylalkyl, C2–C7 haloalkylsulfonylalkyl, C4–C7 alkylthiocycloalkyl, C4–C7 alkylsulfinylcycloalkyl, C4–C7 alkylsulfonylcycloalkyl, C4–C7 haloalkylthiocycloalkyl, C2–C7 haloalkylsulfinylcycloalkyl, C2–C7 haloalkylsulfonylcycloalkyl, C2-C7 alkylsulfoximinoalkyl, C2–C5 cyanoalkyl, C4-C7 cyanocycloalkyl, C1-C4 nitroalkyl, C1-C7 alkylamino, C2-C7 dialkylamino, C3-C5 alkylcarbonyl(alkyl)amino, C3-C5 alkoxycarbonyl(alkyl)amino, C2-C4 alkylsulfonyl(alkyl)amino, C2-C6 alkylcarbonyl, C3-C6 alkylcarbonylalkyl, C2-C6 alkoxycarbonyl, C3-C6 alkoxycarbonylalkyl, C3-C6 trialkylsilyl or C5-C8 trialkylsilylalkynyl; or phenyl, optionally substituted with up to 3 substituents independently selected from the group consisting of halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy;

[0009] R 1b is H, halogen, cyano, nitro, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C3–C5 halocycloalkyl, C2–C4 alkoxyalkyl, C1–C4 alkoxy, C1–C4 alkylthio, or C2–C4 alkoxycarbonyl;

[0010] m is 0, 1, or 2;

[0011] R 1c is H, C1–C7 alkyl, C3–C7 cycloalkyl or C1–C7 haloalkyl;

[0012] X 1 and X 2 Independently N or CR 2 ;

[0013] n is 0, 1, 2, or 3;

[0014] Each R 2 are independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1 – C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 alkylsulfonate, C3–C5 cycloalkylsulfonate, C1–C4 haloalkylsulfonate, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, C2–C5 cyanoalkyl, C4–C6 cyanocycloalkyl, or C2–C5 alkoxycarbonyl; or

[0015] Two adjacent R 2 may together form a saturated or unsaturated 5- to 8-membered ring containing carbon atoms and optionally 1 to 3 oxygen, sulfur or nitrogen atoms as ring members, one or two carbon or sulfur ring members of the heterocyclic ring may optionally be in oxidized form of a carbonyl, sulfonyl, sulfinyl moiety, the ring being unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy;

[0016] Y is O or S;

[0017] R 3ais halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C2–C7 alkylthioalkyl, C2–C7 alkylthioalkyl, Sulfonylalkyl, C2–C7 alkylsulfonylalkyl, C2–C7 haloalkylthioalkyl, C2–C7 haloalkylsulfinylalkyl, C2–C7 haloalkylsulfonylalkyl, C2–C5 cyanoalkyl, C4–C6 cyanocycloalkyl, C1–C4 nitroalkyl, C3–C6 alkylcarbonylalkyl, C2–C6 oxacycloalkyl, C2–C6 oxacycloalkylalkyl, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, or C3–C6 alkoxycarbonylalkyl;

[0018] Each R 3b are independently H, halogen or C1-C3 alkyl; or

[0019] R 3a and R 3b together with the carbon atoms to which they are attached, form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from 1 oxygen atom, 1 sulfur atom and up to 3 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring members are selected from S, S(O) or S(O)2; or

[0020] Two R's 3b together with the carbon atoms to which they are attached, form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from 1 oxygen atom, 1 sulfur atom and up to 3 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring members are selected from S, S(O) or S(O)2;

[0021] p is 0, 1, 2, or 3;

[0022] R 4a is H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, C5–C8 trialkylsilylalkynyl, C1–C5 alkylthio, C1–C5 haloalkylthio, or C2–C5 alkoxycarbonyl;

[0023] q is 0, 1, or 2;

[0024] Each R 4b are independently H, halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 alkylthio;

[0025] Provided that the compound of formula 1 is not:

[0026] [3-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)phenyl](2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-methanone (CAS Reg. No. 1798020-19-5);

[0027] (8-Chloro-2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[3-(1H-tetrazol-1-yl)phenyl]methanone (CAS Reg. No. 2093742-48-2);

[0028] (2-Ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 1808378-56-4);

[0029] (8-Chloro-2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 1808849-41-3);

[0030] (2,3-Dihydro-2,7-dimethyl-4H-1,4-benzoxazin-4-yl)[2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 1436224-65-5);

[0031] (8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[2-(1H-pyrazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 2224006-86-2);

[0032] (2,3-Dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1-pyrrolidinyl)phenyl]methanone (CAS Reg. No. 2733463-68-6);

[0033] Methanone, (3,4-dihydrospiro[2H-1,4-benzoxazin-2,1′-cyclopropane]-4-yl)[3-(1-pyrrolidinyl)phenyl] (CAS Reg. No. 2733410-16-5);

[0034] (2,3-Dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1H-pyrrol-1-yl)phenyl]methanone (CAS Reg. No. 2305402-15-5);

[0035] (3,4-dihydrospiro[2H-1,4-benzoxazine-2,1′-cyclopropane]-4-yl)[3-(1H-pyrrol-1-yl)phenyl]methanone (CAS Reg. No. 2305290-36-0);

[0036] (8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]methanone (CAS Reg. No. 2223792-20-7);

[0037] (7-Fluoro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[2-(4-methyl-1-piperazinyl)-4-pyridinyl]methanone (CAS Reg. No. 2212440-53-2);

[0038] (7-Fluoro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1H-1,2,4-triazol-5-yl)phenyl]methanone (CAS Reg. No. 2094921-82-9);

[0039] (2-Ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1957585-10-2);

[0040] (8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1957541-06-8);

[0041] (8-Chloro-2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1956163-57-7);

[0042] (2,3-Dihydro-2,6-dimethyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1955383-94-4);

[0043] (2,3-Dihydro-2,2-dimethyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1955104-90-1);

[0044] (6-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1954398-26-5);

[0045] (2,3-Dihydro-6-methoxy-2-methyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1947266-43-4); and

[0046] (2,3-Dihydro-6-methoxy-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1H-imidazol-1-yl)phenyl]methanone (CAS Reg. No. 1384688-76-9).

[0047] More specifically, the present invention relates to a compound of formula 1 (including all stereoisomers), its N-oxide or salt. The present invention also relates to a herbicidal composition comprising a compound of the present invention (i.e., in a herbicidally effective amount) and at least one component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent. The present invention also relates to a method for controlling the growth of undesirable vegetation, the method comprising contacting the vegetation or its environment with a herbicidally effective amount of a compound of the present invention (e.g., as a composition described herein).

[0048] The present invention also includes a herbicidal mixture comprising (a) a compound selected from Formula 1, its N-oxide and salt, and (b) at least one additional active ingredient selected from (b1) to (b16), and salts of the compounds (b1) to (b16) as described below. DETAILED DESCRIPTION

[0049] As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains," "containing," "characterized by," or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation expressly stated. For example, a composition, mixture, process, or method that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, or method.

[0050] The transitional phrase "consisting of" excludes any unrecited element, step, or ingredient. If in a claim, this phrase will make the claim closed-ended, excluding materials other than those recited, except for impurities normally associated therewith. When the phrase "consisting of" appears in a clause of the body of a claim rather than immediately following the preamble, the phrase limits only the elements recited in that clause; the claim as a whole does not exclude other elements.

[0051] The conjunction "consisting essentially of" is used to define compositions or methods that include materials, steps, features, components, or elements beyond those literally disclosed, provided that such additional materials, steps, features, components, or elements do not materially affect the basic and novel characteristics of the claimed invention. The term "consisting essentially of" is intermediate between "comprising" and "consisting of."

[0052] When the applicant has defined the present invention or a portion thereof with open-ended terms such as "comprising," it should be readily understood that (unless otherwise indicated) the specification should be interpreted as also describing the invention using the terms "consisting essentially of" or "consisting of."

[0053] In addition, unless expressly stated to the contrary, "or" refers to an inclusive or rather than an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0054] In addition, the indefinite article "a and an" before an element or component of the present invention is intended to be non-restrictive with respect to the number of instances (i.e., occurrences) of the element or component. Therefore, "a or an" should be understood to include one or at least one, and the singular word form of an element or component also includes the plural, unless the number obviously means the singular.

[0055] As referred to herein, the term "seedling" used alone or in combination of words refers to a young plant that develops from the embryo of a seed.

[0056] As referred to herein, the term "broadleaf," used alone or in phrases such as "broadleaf weeds," refers to dicots or dicots, a term used to describe a class of angiosperms characterized by a plumule with two cotyledons.

[0057] As used herein, the term "alkylation" refers to a reaction in which a nucleophile displaces a leaving group such as a halide or sulfonate from a carbon-containing group. Unless otherwise indicated, the term "alkylation" does not limit the carbon-containing group to an alkyl group.

[0058] In the above detailed description, the term "alkyl", used alone or in compound words such as "alkylthio" or "haloalkyl", includes straight or branched alkyl, such as methyl, ethyl, n-propyl, isopropyl or different butyl, pentyl, or hexyl isomers. "Alkenyl" includes straight or branched olefins, such as vinyl, 1-propenyl, 2-propenyl and different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes, such as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight or branched alkynes, such as ethynyl, 1-propynyl, 2-propynyl and different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include a portion consisting of multiple triple bonds, such as 2,5-hexadiynyl.

[0059] “Alkoxy” includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy and different butoxy, pentyloxy and hexyloxy isomers. “Alkoxyalkyl” means alkoxy substitution on alkyl. Examples of “alkoxyalkyl” include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2CH2OCH2 and CH3CH2OCH2CH2. “Hydroxyalkyl” means hydroxy substitution on alkyl. “Hydroxycycloalkyl” means hydroxy substitution on cycloalkyl. “Hydroxyhaloalkyl” means hydroxy substitution on haloalkyl. “Alkoxycycloalkyl” means alkoxy substitution on cycloalkyl. “Alkoxyhaloalkyl” means alkoxy substitution on haloalkyl. Examples of “hydroxyalkyl”, “hydroxycycloalkyl”, “hydroxyhaloalkyl”, “alkoxycycloalkyl”, “alkoxyhaloalkyl” include the following structures

[0060]

[0061] "Alkoxyalkoxy" means that the alkoxy group on the alkoxy group replaces. "Alkylthio" includes branched or straight chain alkylthio moieties, such as methylthio, ethylthio and different propylthio, butylthio, pentylthio and hexylthio isomers. "Alkylthioalkyl" means that the alkylthio group on the alkyl group replaces. Examples of "alkylthioalkyl" include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2, CH3CH2SCH2CH2 and different isomers thereof. "Alkylsulfinyl" includes two enantiomers of alkylsulfinyl. Examples of "alkylsulfinyl" include CH3S(O)-, CH3CH2S(O)-, CH3CH2CH2S(O)-, (CH3)2CHS(O)- and different butylsulfinyl, pentylsulfinyl and hexylsulfinyl isomers. Examples of "alkylsulfonyl" include CH3S(O)2-, CH3CH2S(O)2-, CH3CH2CH2S(O)2-, (CH3)2CHS(O)2-, and different butylsulfonyl, pentylsulfonyl and hexylsulfonyl isomers. Examples of "alkylsulfonates" include CH3S(O)2O-, CH3CH2S(O)2O-, CH3CH2CH2S(O)2O-, (CH3)2CHS(O)2O-, and different butylsulfonates, pentylsulfonates and hexylsulfonate isomers. "Cyanoalkyl" refers to an alkyl group substituted with a cyano group. Examples of "cyanoalkyl" include NCCH2 and NCCH2CH2 (alternatively identified as CH2CH2CN). "Nitroalkyl" refers to an alkyl group substituted with a nitro group. Examples of "nitroalkyl" include NO2CH2 and NO2CH2CH2 (alternatively identified as CH2CH2NO2). "Cyano" means NC-, and "formyl" means HC(=O)-. "Alkylamino" includes NH groups substituted by straight or branched alkyl groups. Examples of "alkylamino" include CH3CH2NH, CH3CH2CH2NH and (CH3)2CHCH2NH. Examples of "dialkylamino" include (CH3)2N, (CH3CH2CH2)2N and CH3CH2(CH3)N. "Alkylsilyl" includes silyl groups substituted by straight or branched alkyl groups. "Trialkylsilyl" includes silyl groups substituted by three straight or branched alkyl groups. Examples of "trialkylsilyl" include (CH3)3Si- and (CH3CH2)3Si-. "Trialkylsilylalkynyl" means trialkylsilyl substitution on alkynyl. Examples of "trialkylsilylalkynyl" include (CH3)3SiC≡C- and (CH3CH2)3SiC≡C-.

[0062] "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term "cycloalkylalkyl" means cycloalkyl substitution on the alkyl part. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl parts bonded to straight or branched alkyl groups. The term "alkylcycloalkyl" means an alkyl group bonded to a cycloalkyl part. The term "cycloalkyl" means a cycloalkyl bonded through oxygen. Examples of "cycloalkoxy" include cyclopropyloxy, cyclobutyloxy and cyclopentyloxy. The term "cycloalkoxyalkyl" means cycloalkoxy substitution on the alkyl part. Examples of "cycloalkoxyalkyl" include cyclopropyloxymethyl, cyclobutyloxyethyl and cyclopentyloxymethyl, and other cycloalkoxy parts bonded to straight or branched alkyl groups. The term "oxacycloalkyl" means a cycloalkyl group having a carbon ring member replaced by an oxygen atom. Examples of "oxacycloalkyl" include oxacyclopropyl, oxacyclobutyl and oxacyclopentyl. The term "thiacycloalkyl" represents a cycloalkyl having a carbon ring member substituted by a sulfur atom. Examples of "thiacycloalkyl" include thiacyclopropyl, thiacyclobutyl and thiacyclopentyl. The term "(O-thia)cycloalkyl" represents a cycloalkyl having a carbon ring member substituted by a -SO group. Examples of "(O-thia)cycloalkyl" include (O-thia)cyclopropyl, (O-thia)cyclobutyl and (O-thia)cyclopentyl. The term "(O2thia)cycloalkyl" represents a cycloalkyl having a carbon ring member substituted by a -SO2 group. Examples of "(O2thia)cycloalkyl" include (O2thia)cyclopropyl, (O2thia)cyclobutyl and (O2thia)cyclopentyl.

[0063] The term "halogen", alone or in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted by halogen", includes fluorine, chlorine, bromine or iodine. In addition, when used in compound words such as "haloalkyl", or when used in descriptions such as "alkyl substituted by halogen", the alkyl group may be partially or completely substituted by halogen atoms (which may be the same or different). Examples of "haloalkyl" or "alkyl substituted by halogen" include F3C, ClCH2, CF3CH2 and CF3CCl2. The terms "haloalkoxy", "haloalkoxyalkyl", "haloalkylthio", "haloalkenyl", "haloalkynyl", "halocycloalkyl", "haloalkylcycloalkyl", "haloalkylsulfinyl", "haloalkylsulfonyl" and the like are defined similarly to the term "haloalkyl". Examples of "haloalkoxy" include CF3O-, CCl3CH2O-, HCF2CH2CH2O- and CF3CH2O-. Examples of "haloalkoxyalkyl" include CF3OCH2-, CCl3CH2OCH2-, HCF2CH2CH2OCH2-, and CF3CH2OCH2-. Examples of "haloalkylthio" include CCl3S-, CF3S-, CCl3CH2S-, and ClCH2CH2CH2S-. Examples of "haloalkenyl" include (Cl)2C=CH-(Cl)2C=CHCH2-, and CF3CH2CH=CHCH2-. Examples of "haloalkynyl" include HC≡CCHCl-, CF3C≡C-, CCl3C≡C-, and FCH2C≡CCH2-. Examples of "halocycloalkyl" include 1-chlorocyclopropyl, 2-chlorocyclopropyl, 2-fluorocyclopropyl, 1-chlorocyclobutyl, 1-fluorocyclobutyl, and 2-fluorocyclobutyl. Examples of "haloalkylcycloalkyl" include 1-(chloromethyl)cyclopropyl, 2-(chloromethyl)cyclopropyl, 2-(fluoromethyl)cyclopropyl, 1-(chloromethyl)cyclobutyl, 2-(fluoroethyl)cyclobutyl and 2-(fluoromethyl)cyclobutyl.

[0064] "Alkylcarbonyl" means a straight or branched alkyl moiety bonded to a C(=O) moiety. Examples of "alkylcarbonyl" include CH3C(=O)-, CH3CH2C(=O)-, CH3CH2CH2C(=O)-, (CH3)2CHC(=O)-, and different butyl- or pentylcarbonyl isomers. "Alkoxycarbonyl" means a straight or branched alkoxy moiety bonded to a C(=O) moiety. Examples of "alkoxycarbonyl" include CH3OC(=O)-, CH3CH2OC(=O)-, CH3CH2CH2OC(=O)-, (CH3)2CHOC(=O)-, and different butoxy- or pentyloxy-carbonyl isomers. C(=O) or C(O) represents a carbonyl group. The term "alkoxycarbonylalkyl" means a straight or branched alkoxycarbonyl moiety bonded through an alkyl moiety. The term "alkylcarbonylalkyl" refers to a straight or branched alkylcarbonyl moiety bonded through an alkyl moiety. The term "alkylcarbonyloxy" refers to an alkylcarbonyl moiety bonded through oxygen. Examples of alkylcarbonyloxy include CH3C(=O)O-, CH3CH2C(=O)O-, CH3CH2CH2C(=O)O-, and (CH3)2CHC(=O)-. The term "alkenyloxy" refers to an alkenyl moiety bonded through oxygen. Examples of "alkenyloxy" include CH2=CHCH2O-, 1-propenyloxy or CH3CH=CHO-, 2-butenyloxy or CH3CH=CHCH2O-, and different butenyloxy, pentenyloxy and hexenyloxy isomers. Examples of "alkenyloxy" may also contain more than one double bond. The term "alkynyloxy" refers to an alkynyl moiety bonded through oxygen. Examples of "alkynyloxy" include CHCCH2O-, 1-propynyloxy or CH3CCO-, 2-butynyloxy or CH3CCCH2O-, and different butynyloxy, pentynyloxy and hexynyloxy isomers. Examples of "alkynyloxy" may also contain more than one triple bond. The term alkanediyl or alkenediyl refers to a straight or branched alkane or alkene linking chain, respectively. Examples of "alkanediyl" include -CH2-, -CH2CH(CH3)-, or -CH2CH2CH2-. Examples of "alkenediyl" include -CH=CH-, -CH2C=CH-, or -CH=C(CH3)-. In the context of positioning substituents, the term "adjacent" means "immediately adjacent to" or "directly adjacent to".

[0065] "Alkylsulfoximinoalkyl" means an alkylsulfoximine or cycloalkylsulfoximine substitution on an alkyl or cycloalkyl group. Examples of "alkylsulfoximinoalkyl" include the following structures:

[0066]

[0067] The total number of carbon atoms in a substituent group is represented by "C i –C j" prefix indicates, where i and j are numbers from 1 to 8. For example, C1-C4 alkylsulfonyl represents methylsulfonyl to butylsulfonyl; C3-C8 alkylcarbonylalkyl can be, for example, CH3COCH2-, CH3COCH2CH2-, or CH3CH2CH2COCH2CH2CH2CH2-; C4-C7 alkylcycloalkyl can be, for example, methylcyclopropyl, methylcyclobutyl, ethylcyclopropyl, or propylcyclobutyl; C2 alkoxyalkyl specifies CH3OCH2-; C3 alkoxyalkyl specifies, for example, CH3CH(OCH3)-, CH3OCH2CH2-, or CH3CH2OCH2-; and C4 alkoxyalkyl specifies various isomers of alkyl substituted with alkoxy groups containing a total of four carbon atoms, examples of which include CH3CH2CH2OCH2- and CH3CH2OCH2CH2-.

[0068] When a group contains a substituent which may be hydrogen, such as R 2 or R 5 When the substituent is hydrogen, it is recognized that this is equivalent to the group being unsubstituted. When one or more positions on a group are referred to as being "not substituted" or "unsubstituted", hydrogen atoms are attached to occupy any free valences. Unless otherwise specified as optionally substituted, the term "phenyl" means unsubstituted phenyl. Unless otherwise specified as optionally substituted, the term "benzyl" means unsubstituted benzyl.

[0069] When a compound is substituted with substituents bearing a subscript indicating that the number of said substituents may exceed 1, said substituents (when they exceed 1) are independently selected from the defined group of substituents, e.g., (R 3b ) p , wherein n is 0, 1, 2 or 3. When p is 0, a hydrogen may be present at that position even if not recited in the definition of a substituent. When a functional group or compound is shown to be optionally substituted with a substituent, the functional group or compound may be unsubstituted or substituted. When one or more positions on a group are referred to as being "not substituted" or "unsubstituted," a hydrogen atom is attached to occupy any free valences.

[0070] (R 3b ) p The attachment points are shown as floating. Each R 3b Attachment can be via a replacement hydrogen atom to any of the three available aromatic carbons.

[0071] The term "ring system" refers to two or more fused rings. The term "bicyclic ring system" refers to a ring system consisting of two fused rings.

[0072] The compounds of the present invention may exist as one or more stereoisomers. Various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. Stereoisomers are isomers with the same composition but different arrangements of their atoms in space, and include enantiomers, diastereomers, cis-trans isomers (also referred to as geometric isomers) and atropisomers. Atropisomers are caused by restricted rotation around a single bond, where the rotation barrier is high enough to allow separation of isomeric species. It will be understood by those skilled in the art that a stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to one or more other stereoisomers, or when separated from one or more other stereoisomers. In addition, those skilled in the art know how to separate, enrich and / or selectively prepare the stereoisomers. The compounds of the present invention may exist as a mixture of stereoisomers, a single stereoisomer, or as an optically active form.

[0073] The compounds of formula 1 typically exist in more than one form, and therefore formula 1 includes all crystalline and non-crystalline forms of the compounds they represent. Non-crystalline forms include solid embodiments such as waxes and gums, and liquid embodiments such as solutions and melts. Crystalline forms include embodiments representing substantially single crystal types and embodiments representing mixtures of polymorphs (i.e., different crystalline types). The term "polymorph" refers to a specific crystalline form of a compound that can be crystallized in different crystalline forms, which have different molecular arrangements and / or conformations in the crystal lattice. Although polymorphs may have the same chemical composition, they may also differ in composition due to the presence or absence of co-crystallized water or other molecules, which may be weakly or strongly bound to the crystal lattice. Polymorphs may differ in such chemical, physical, and biological properties, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspendability, dissolution rate, and bioavailability. Those skilled in the art will appreciate that a polymorph of a compound of Formula 1 may exhibit beneficial effects (e.g., suitability for preparing useful formulations, improved biological performance) relative to another polymorph or mixture of polymorphs of the same compound of Formula 1. The preparation and separation of a specific polymorph of a compound of Formula 1 may be accomplished by methods known to those skilled in the art, including, for example, crystallization using a selected solvent and temperature. For a comprehensive discussion of polymorphism, see R. Hilfiker, ed., Polymorphism in the Pharmaceutical Industry, Wiley-VCH, Weinheim, 2006.

[0074] Those skilled in the art will appreciate that not all nitrogen-containing heterocycles can form N-oxides, since nitrogen requires an available lone electron pair to oxidize to an oxide; those skilled in the art will recognize those nitrogen-containing heterocycles that can form N-oxides. Those skilled in the art will also recognize that tertiary amines are capable of forming N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art, including oxidation of heterocycles and tertiary amines using peroxyacids such as peracetic acid and meta-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These methods for preparing N-oxides have been extensively described and reviewed in the literature, see, for example: T.L. Gilchrist, Comprehensive Organic Synthesis, Vol. 7, pp. 748-750, ed. S.V. Ley, Pergamon Press; M. Tisler and B. Stanovnik, Comprehensive Heterocyclic Chemistry, Vol. 3, pp. 18-20, ed. A.J. Boulton and A. McKillop, Pergamon Press; M.R. Grimmett and B.R.T. Keene, Advances in Heterocyclic Chemistry, Vol. 43, pp. 149-161, ed. A.R. Katritzky, Academic Press; M. Tisler and B. Stanovnik, Advances in Heterocyclic Chemistry, Vol. 43, pp. 149-161, ed. A.R. Katritzky, Academic Press; Chemistry, vol. 9, pp. 285-291, AR Katritzky and AJ Boulton, eds., Academic Press; and GWH Cheeseman and ESG Werstiuk, Advances in Heterocyclic Chemistry, vol. 22, pp. 390-392, AR Katritzky and AJ Boulton, eds., Academic Press.

[0075] Those skilled in the art recognize that, since the salt of the compound is in balance with their corresponding non-salt form in the environment and under physiological conditions, the salt shares the biological utility of the non-salt form. Therefore, the salt of the compound of multiple formula 1 can be used to control undesirable vegetation (that is, suitable in agriculture). The salt of the compound of formula 1 includes an acid addition salt formed with an inorganic acid or an organic acid, and the acid is such as hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, butyric acid, fumaric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, salicylic acid, tartaric acid, 4-toluenesulfonic acid or valeric acid. When the compound of formula 1 contains an acidic part, the salt also includes those formed with an organic base or an inorganic base, and these bases are such as pyridine, triethylamine or ammonia or sodium, potassium, lithium, calcium, magnesium or barium amide, hydride, hydroxide or carbonate. Therefore, the present invention includes compounds selected from formula 1, its N-oxide and suitable salts in agriculture.

[0076] As mentioned above, two adjacent R 2 The 5- to 8-membered ring may be formed together, and the 5- to 8-membered ring may be (among other things) saturated or unsaturated, optionally substituted with one or more substituents selected from the group of substituents as defined in the Summary of the Invention. Examples of 5- to 8-membered unsaturated aromatic rings optionally substituted with one or more substituents include rings U-1 to U-60 shown in Example 1, wherein R v are independently H, halogen, cyano, nitro, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, and C1-C4 haloalkoxy, and r is an integer from 0 to 2, limited by the number of available positions on each U group. The U groups may share any two available adjacent atoms with the connecting ring.

[0077] Example 1

[0078]

[0079]

[0080]

[0081] It should be noted that when the 5- to 8-membered saturated or unsaturated non-aromatic heterocyclic ring is optionally replaced by one or more selected from the group consisting of 2 When substituted with a substituent of the defined group of substituents, one or both carbon ring members of the heterocyclic ring may optionally be in oxidized form of the carbonyl moiety.

[0082] is a saturated or non-aromatic unsaturated heterocyclic ring containing ring members selected from up to two O atoms and up to two S atoms and optionally in the presence of up to four R vExamples of 5- to 8-membered heterocyclic rings substituted on carbon atom ring members include rings T-1 to T-35, as shown in Example 2. It should be noted that the T group can share any two available adjacent atoms with the connecting ring. v The optional substituents of can be attached to any available carbon or nitrogen by replacing a hydrogen atom. For these T rings, r is typically an integer from 0 to 4, limited by the number of available positions on each T group. The term "optionally substituted" means "substituted or unsubstituted". It should be noted that when T 2 When N is present, the nitrogen atom may be replaced by H or by R as defined in the Summary of the Invention. v The substituents replace to complete its valence.

[0083] Example 2

[0084]

[0085]

[0086] Although R is shown in structures U-1 to U-60 and T1-T35 v groups, but it should be noted that since they are optional substituents, they do not have to be present. It should be noted that when R v When H is attached to an atom, this is as if the atom is unsubstituted. The nitrogen atom that needs substitution to fill its valency is replaced by H or R v It should be noted that when (R v ) r When the attachment point between the U (or T) group is shown as floating, (R v ) r Attachment may be made to any available carbon atom or nitrogen atom of the U group.

[0087] A variety of synthetic methods are known in the art that allow the preparation of aromatic and nonaromatic heterocycles and ring systems; for extensive reviews, see the eight-volume collection Comprehensive Heterocyclic Chemistry, edited by AR Katritzky and CW Rees, Pergamon Press, Oxford, 1984, and the twelve-volume collection Comprehensive Heterocyclic Chemistry II, edited by AR Katritzky, CW Rees and EF V Scriven, Pergamon Press, Oxford, 1996.

[0088] Embodiments of the invention as described in the Summary of the Invention include those described below. In the following Examples, unless further defined in the Examples, Formula 1 includes stereoisomers, N-oxides and salts thereof, and references to "compounds of Formula 1" include definitions of substituents specified in the Summary of the Invention.

[0089] Example 1. A compound of formula 1, its stereoisomers, N-oxides and salts, agricultural compositions containing them and their use as herbicides, as described in the Summary of the Invention.

[0090] A

[0091] Embodiment 2X. The compound of formula 1 as described in embodiment 1, wherein

[0092] A is selected from

[0093]

[0094]

[0095]

[0096] Embodiment 2. A compound as described in Embodiment 2X, wherein A is A-1, A-2, A-3, A-4, A-5, A-6, A-7, A-8, A-9, A-10, A-11, A-12 or A-13.

[0097] Embodiment 2a. A compound as described in Embodiment 2, wherein A is A-1, A-2, A-3, A-4, A-5, A-7, A-8, A-9, A-10, A-11, A-12 or A-13.

[0098] Embodiment 2aa. The compound as described in Embodiment 2a, wherein A is A-1, A-3, A-4, A-5, A-12 or A-13.

[0099] Embodiment 2aaa. The compound as described in Embodiment 2aa, wherein A is A-1, A-4 or A-5.

[0100] Embodiment 2b. The compound as described in Embodiment 2a, wherein A is A-1.

[0101] Embodiment 2c. The compound as described in Embodiment 2a, wherein A is A-2.

[0102] Embodiment 2d. The compound as described in Embodiment 2a, wherein A is A-3.

[0103] Embodiment 2e. The compound as described in Embodiment 2a, wherein A is A-4.

[0104] Embodiment 2f. The compound as described in Embodiment 2a, wherein A is A-5.

[0105] Embodiment 2g. The compound as described in Embodiment 2a, wherein A is A-7.

[0106] Embodiment 2h. The compound as described in Embodiment 2a, wherein A is A-8.

[0107] Embodiment 2i. The compound as described in Embodiment 2a, wherein A is A-9.

[0108] Embodiment 2j. The compound as described in Embodiment 2a, wherein A is A-10.

[0109] Embodiment 2k. The compound as described in Embodiment 2a, wherein A is A-11.

[0110] Embodiment 21. The compound as described in Embodiment 2a, wherein A is A-12.

[0111] Embodiment 2m. The compound as described in Embodiment 2a, wherein A is A-13.

[0112] Embodiment 2n. A compound as described in Embodiment 2X, wherein A is A-1, A-2, A-3, A-4, A-5, A-6, A-7, A-8, A-9, A-10, A-11, A-12, A-13, A-14, A-15, A-16 or A-17.

[0113] Embodiment 2o. A compound as described in Embodiment 2n, wherein A is A-1, A-3, A-4, A-5, A-11, A-12, A-13, A-14, A-15, A-16 or A-17.

[0114] Embodiment 2p. A compound as described in Embodiment 2o, wherein A is A-1, A-4, A-5, A-12, A-14, A-15 or A-17.

[0115] Embodiment 2q. The compound as described in Embodiment 2p, wherein A is A-1, A-4 or A-15.

[0116] X 1 and X 2

[0117] Embodiment 3. The compound of formula 1 as described in embodiment 1, wherein X 1 and X 2 Independently N or CR 2 ;

[0118] Embodiment 3a. The compound as described in Embodiment 3, wherein X 1 and X 2Both are CR 2 .

[0119] Embodiment 3b. The compound as described in Embodiment 3, wherein X 1 is N and X 2

[0120] Yes CR 2 .

[0121] Embodiment 3c. The compound as described in Embodiment 3, wherein X 1 Yes CR 2 And X 2 It is N.

[0122] Embodiment 3d. The compound as described in Embodiment 3, wherein X 1 and X 2 Both are N.

[0123] R 1a

[0124] Embodiment 4. The compound of formula 1 as described in embodiment 1, wherein R 1a is H, halogen, cyano, nitro, amino, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkoxy, C4–C7 cycloalkoxyalkyl, C1–C7 haloalkoxy, C1–C7 alkylthio, C2–C7 alkylthioalkyl, C1–C5 alkylsulfinyl, C1–C5 alkylsulfonyl, or C1–C5 haloalkylthio.

[0125] Embodiment 4a. The compound as described in Embodiment 4, wherein R 1ais H, halogen, cyano, nitro, amino, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl Cycloalkyl, C3–C7 oxacycloalkylalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkoxyalkyl, or C1–C7 haloalkoxy.

[0126] Embodiment 4b. The compound as described in embodiment 4a, wherein R 1a is H, halogen, cyano, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl , C3–C7 oxacycloalkylalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkoxyalkyl, or C1–C7 haloalkoxy.

[0127] Embodiment 4c. The compound as described in embodiment 4b, wherein R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, or C1–C7 haloalkoxy.

[0128] Embodiment 4d. The compound as described in Embodiment 4c, wherein R 1ais H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C4 hydroxyalkyl, C3–C5 hydroxycycloalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl.

[0129] Embodiment 4e. The compound as described in embodiment 4d, wherein R 1a It is H, Me, Et, i-Pro, i-Bu, Bu, t-Bu, Br, cyano, c-Bu, c-Pen, c-Hex, HOCH2, HOC(Me)2, CH2OMe, CH2O-i-Pro, CH2CH2OMe, CH2-c-Hex or 3-oxetanyl.

[0130] Embodiment 4f. The compound as described in embodiment 4d, wherein R 1a It's H.

[0131] Embodiment 4g. The compound as described in Embodiment 4d, wherein R 1a It is a C1–C7 alkyl group.

[0132] Embodiment 4h. The compound as described in Embodiment 4g, wherein R 1a It is Et, i-Pro or t-Bu.

[0133] Embodiment 4i. The compound as described in Embodiment 4d, wherein R 1a It is a C3–C7 cycloalkyl group.

[0134] Embodiment 4j. The compound as described in embodiment 4i, wherein R 1a It's c-Bu.

[0135] Embodiment 4k. The compound as described in Embodiment 4g, wherein R 1a It's me.

[0136] Embodiment 41. The compound of formula 1 as described in embodiment 1, wherein R 1ais H, halogen, cyano, nitro, amino, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C3–C7 alkyloxacycloalkyl, C2–C6 thiacycloalkyl, C3–C7 thiacycloalkylalkyl, C3–C7 alkylthiacycloalkyl, C2–C6 (O-thia)cycloalkyl, C3–C7 (O-thia)cycloalkyl Alkylalkyl, C3–C7 alkyl(O-thia)cycloalkyl, C2–C6(O2thia)cycloalkyl, C3–C7(O2thia)cycloalkylalkyl, C3–C7 alkyl(O2thia)cycloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C1–C7 haloalkoxy, C1–C7 alkylthio, C2–C7 alkylthioalkyl, C1–C5 alkylsulfinyl, C1–C5 alkylsulfonyl C1–C4 alkylsulfonate, C1–C5 haloalkylthio, C1–C5 haloalkylsulfinyl, C1–C5 haloalkylsulfonyl, C2–C7 alkylsulfinylalkyl, C2–C7 alkylsulfonylalkyl, C2–C7 haloalkylthioalkyl, C2–C7 haloalkylsulfinylalkyl, C2–C7 haloalkylsulfonylalkyl, C4–C7 alkylthiocycloalkyl, C4–C7 alkylsulfinylcycloalkyl, C4–C7 alkylsulfonylcycloalkyl, C4–C7 haloalkylthiocycloalkyl, C2–C7 haloalkylsulfinylcycloalkyl, C2–C7 haloalkylsulfonylcycloalkyl, C2-C7 alkylsulfonylcycloalkyl, C2-C7 alkylsulfoiminoalkyl, C2–C5 cyanoalkyl, C4–C C7-cyanocycloalkyl, C1-C4 nitroalkyl, C1-C7 alkylamino, C2-C7 dialkylamino, C3-C5 alkylcarbonyl(alkyl)amino, C3-C5 alkoxycarbonyl(alkyl)amino, C2-C4 alkylsulfonyl(alkyl)amino, C2-C6 alkylcarbonyl, C3-C6 alkylcarbonylalkyl, C2-C6 alkoxycarbonyl, C3-C6 alkoxycarbonylalkyl, C3-C6 trialkylsilyl or C5-C8 trialkylsilylalkynyl; or phenyl, optionally substituted with up to 3 substituents independently selected from the group consisting of halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy;

[0137] R 1b

[0138] Embodiment 5. The compound of formula 1 as described in embodiment 1, wherein R 1b is H, halogen, cyano, nitro, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C3–C5 halocycloalkyl, C2–C4 alkoxyalkyl, C1–C4 alkoxy, C1–C4 alkylthio, or C2–C4 alkoxycarbonyl.

[0139] Embodiment 5a. The compound of embodiment 5, wherein R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C3–C5 halocycloalkyl, C2–C4 alkoxyalkyl, C1–C4 alkoxy, or C2–C4 alkoxycarbonyl.

[0140] Embodiment 5b. The compound as described in Embodiment 5a, wherein R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl.

[0141] Embodiment 5c. The compound as described in Embodiment 5b, wherein R 1b is H, Me, i-Pro, CN, CF3, F or Cl.

[0142] Embodiment 5d. The compound as described in Embodiment 5c, wherein R 1b It's H.

[0143] m

[0144] Embodiment 6. The compound of formula 1 as described in embodiment 1, wherein m is 0, 1, or 2.

[0145] Embodiment 6a. The compound as described in Embodiment 6, wherein m is 0.

[0146] Embodiment 6b. The compound as described in Embodiment 6, wherein m is 1.

[0147] Embodiment 6c. The compound as described in Embodiment 6, wherein m is 2.

[0148] R 1c

[0149] Embodiment 7. The compound of formula 1 as described in embodiment 1, wherein R 1c is H, C1–C7 alkyl, C3–C7 cycloalkyl or C1–C7 haloalkyl.

[0150] Embodiment 7a. The compound as described in Embodiment 7, wherein R 1c is H or C1–C7 alkyl,

[0151] Embodiment 7b. The compound as described in embodiment 7a, wherein R 1c It is H, Me or i-Pro.

[0152] Embodiment 7c. The compound as described in embodiment 7b, wherein R 1c It's H.

[0153] Embodiment 7d. The compound as described in embodiment 7b, wherein R 1c It's me.

[0154] Embodiment 7e. The compound as described in embodiment 7b, wherein R 1c It's i-Pro.

[0155] n

[0156] Embodiment 8. The compound of formula 1 as described in embodiment 1, wherein n is 0, 1, 2 or 3.

[0157] Embodiment 8a. The compound as described in Embodiment 8, wherein n is 0.

[0158] Embodiment 8b. The compound as described in Embodiment 8, wherein n is 1.

[0159] Embodiment 8c. The compound as described in Embodiment 8, wherein n is 2.

[0160] Embodiment 8d. The compound as described in Embodiment 8, wherein n is 3.

[0161] R 2

[0162] Embodiment 9. The compound of formula 1 as described in embodiment 1, wherein R 2 is independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 alkylsulfonate, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, or C2–C5 alkoxycarbonyl; or

[0163] Two adjacent R 2The alkyl groups may together form a 5- or 6-membered ring containing carbon atoms and optionally 1 to 2 oxygen atoms, sulfur atoms or nitrogen atoms as ring members, the ring being unsubstituted or substituted by at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy.

[0164] Embodiment 9a. The compound as described in Embodiment 9, wherein R 2 and alkyl. are independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, C1–C4 alkylsulfonate, or C2–C5 alkoxycarbonyl.

[0165] Embodiment 9a. The compound as described in Embodiment 9, wherein R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy.

[0166] Embodiment 9b. The compound as described in Embodiment 9a, wherein R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 alkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy.

[0167] Embodiment 9c. The compound as described in Embodiment 9a, wherein R 2 are independently H, halogen, cyano, OH, C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C3-C6 cycloalkyl, C1-C5 haloalkyl, C1-C5 alkoxy, or C1-C5 haloalkoxy.

[0168] Embodiment 9d. The compound as described in Embodiment 9c, wherein R 2 are independently H, C1-C5 alkyl or C1-C5 alkoxy.

[0169] Embodiment 9d. The compound as described in Embodiment 9c, wherein R 2 is independently H, OH, CN, OEt, propargyl, allyl, c-Pro, F, Cl, Br, CN, Me, Et, OMe, CF3, OCF3 or CH2CF3.

[0170] Embodiment 9e. The compound as described in Embodiment 9d, wherein R 2 is independently H, Me or Et.

[0171] Embodiment 9f. The compound as described in Embodiment 9e, wherein R 2 Independently H.

[0172] Embodiment 9g. The compound as described in Embodiment 9f, wherein R 2 Independently, it is Me.

[0173] Embodiment 9h. The compound as described in Embodiment 9g, wherein R 2 Independently, Et.

[0174] Embodiment 9i. The compound as described in Embodiment 9, wherein two adjacent R 2 The alkyl groups may together form a 5- or 6-membered ring containing carbon atoms and optionally 1 to 2 oxygen atoms, sulfur atoms or nitrogen atoms as ring members, the ring being unsubstituted or substituted by at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy.

[0175] Embodiment 9j. The compound of formula 1 as described in embodiment 1, wherein each R 2are independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1 – C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 alkylsulfonate, C3–C5 cycloalkylsulfonate, C1–C4 haloalkylsulfonate, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, C2–C5 cyanoalkyl, C4–C6 cyanocycloalkyl, or C2–C5 alkoxycarbonyl; or

[0176] Two adjacent R 2 The heterocyclic ring may together form a saturated or unsaturated 5- to 8-membered ring containing carbon atoms and optionally 1 to 3 oxygen, sulfur or nitrogen atoms as ring members, one or two carbon or sulfur ring members of the heterocyclic ring may optionally be in an oxidized form of a carbonyl, sulfonyl, sulfinyl moiety, the ring being unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy.

[0177] Embodiment 9k. The compound as described in Embodiment 9j, wherein R 2 The heterocyclic ring may together form a saturated or unsaturated 5- to 8-membered ring containing carbon atoms and optionally 1 to 3 oxygen, sulfur or nitrogen atoms as ring members, one or two carbon or sulfur ring members of the heterocyclic ring may optionally be in an oxidized form of a carbonyl, sulfonyl, sulfinyl moiety, the ring being unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy.

[0178] Embodiment 91. The compound as described in Embodiment 9k, wherein R 2 Together they may form a 5- or 6-membered ring containing up to 2 oxygen atoms as ring members.

[0179] Y

[0180] Embodiment 10. The compound of formula 1 as described in embodiment 1, wherein Y is O or S.

[0181] Embodiment 10a. The compound as described in Embodiment 10, wherein Y is O.

[0182] Embodiment 10b. The compound as described in Embodiment 10, wherein Y is S.

[0183] R 3a

[0184] Embodiment 11. The compound of formula 1 as described in embodiment 1, wherein R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C2–C7 alkylthioalkyl, C2–C7 haloalkylthioalkyl, C2–C5 cyanoalkyl, C4–C7 cyanocycloalkyl, C1–C4 nitroalkyl, C3–C6 alkylcarbonylalkyl, C2–C6 oxacycloalkyl, C3–C7 cycloalkyloxy, or C3–C6 alkoxycarbonylalkyl.

[0185] Embodiment 11a. The compound as described in Embodiment 11, wherein R 3a are independently halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl or C2–C7 haloalkoxyalkyl.

[0186] Embodiment 11b. The compound as described in embodiment 11a, wherein R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl.

[0187] Embodiment 11c. The compound as described in embodiment 11b, wherein R 3a It is C1–C7 alkyl, C3–C7 cycloalkyl, C1–C7 haloalkyl or C2–C7 alkoxyalkyl.

[0188] Embodiment 11d. The compound as described in embodiment 11c, wherein R 3ais Me, Et, Pro, i-Pro, CF3, CH2F or CH2OMe.

[0189] Embodiment 11e. The compound as described in embodiment 11d, wherein R 3a It's me.

[0190] Embodiment 11f. The compound of formula 1 as described in embodiment 1, wherein R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C2–C7 alkylthioalkyl, C2–C7 alkylthioalkyl, Sulfonylalkyl, C2–C7 alkylsulfonylalkyl, C2–C7 haloalkylthioalkyl, C2–C7 haloalkylsulfinylalkyl, C2–C7 haloalkylsulfonylalkyl, C2–C5 cyanoalkyl, C4–C6 cyanocycloalkyl, C1–C4 nitroalkyl, C3–C6 alkylcarbonylalkyl, C2–C6 oxacycloalkyl, C2–C6 oxacycloalkylalkyl, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, or C3–C6 alkoxycarbonylalkyl.

[0191] Embodiment 11g. The compound as described in embodiment 11f, wherein R 3a is halogen or C1–C7 alkyl.

[0192] Embodiment 11h. The compound as described in embodiment 11g, wherein R 3a It is F, Cl or Me.

[0193] R 3b

[0194] Embodiment 12. The compound of formula 1 as described in embodiment 1, wherein R 3b is H or halogen.

[0195] Embodiment 12a. The compound as described in Embodiment 12, wherein R 3b It's H.

[0196] Embodiment 12b. The compound as described in Embodiment 12, wherein R 3b It's a halogen.

[0197] Embodiment 12c. The compound of formula 1 as described in embodiment 1, wherein R 3b are independently H, halogen or C1-C3 alkyl; or

[0198] R3a and R 3b together with the carbon atoms to which they are attached, form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from 1 oxygen atom, 1 sulfur atom and up to 3 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring members are selected from S, S(O) or S(O)2; or

[0199] Two R's 3b Together with the carbon atoms to which they are attached, they form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from 1 oxygen atom, 1 sulfur atom and up to 3 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S), and the sulfur atom ring members are selected from S, S(O) or S(O)2.

[0200] p

[0201] Embodiment 13. The compound of formula 1 as described in embodiment 1, wherein p is 0, 1, 2 or 3.

[0202] Embodiment 13a. The compound as described in Embodiment 13, wherein p is 0.

[0203] Embodiment 13b. The compound as described in Embodiment 13, wherein p is 1.

[0204] Embodiment 13c. The compound as described in Embodiment 13, wherein p is 2.

[0205] Embodiment 13d. The compound as described in Embodiment 13, wherein p is 3.

[0206] R 4a

[0207] Embodiment 14. The compound of formula 1 as described in embodiment 1, wherein R 4a is H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, C5–C8 trialkylsilylalkynyl, C1–C5 alkylthio, C1–C5 haloalkylthio, or C2–C5 alkoxycarbonyl.

[0208] Embodiment 14a. The compound as described in Embodiment 14, wherein R 4ais H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, or C5–C8 trialkylsilylalkynyl.

[0209] Embodiment 14b. The compound as described in Embodiment 14a, wherein R 4a is H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, or C5–C8 trialkylsilylalkynyl.

[0210] Embodiment 14c. The compound as described in Embodiment 14b, wherein R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 alkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, or C5–C8 trialkylsilylalkynyl.

[0211] Embodiment 14d. The compound as described in Embodiment 14c, wherein R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl.

[0212] Embodiment 14e. The compound as described in Embodiment 14d, wherein R 4a It is H, CN, NO2, F, Cl, Br, Me, Et, CF3, CH2F, OCF3, OMe, CH2OMe, CH=CH2, C≡CSiMe3, C≡CH or c-Pro.

[0213] Embodiment 14f. The compound as described in Embodiment 14e, wherein R 4a It is H, F, Cl, Br, Me, Et, CF3, OCF3, OMe, CH2OMe, CH=CH2, C≡CH or c-Pro.

[0214] Embodiment 14g. The compound as described in Embodiment 14e, wherein R 4aIt is Cl or Me.

[0215] R 4b

[0216] Embodiment 15. The compound of formula 1 as described in embodiment 1, wherein R 4b is H, halogen, cyano, nitro, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 alkoxy, or C1–C4 alkylthio.

[0217] Embodiment 15a. The compound as described in Embodiment 15, wherein R 4b is H, halogen, cyano, C1–C4 alkyl, C1–C4 haloalkyl, or C1–C4 alkoxy.

[0218] Embodiment 15b. The compound as described in Embodiment 15a, wherein R 4b is H or halogen.

[0219] Embodiment 15c. The compound as described in Embodiment 15b, wherein R 4b It is H, F or Cl.

[0220] Embodiment 15d. The compound as described in Embodiment 15c, wherein R 4b It's H.

[0221] Embodiment 15e. The compound as described in Embodiment 15c, wherein R 4b It's F.

[0222] Embodiment 15f. The compound as described in Embodiment 15c, wherein R 4b It is Cl.

[0223] q

[0224] Embodiment 16. The compound of formula 1 as described in embodiment 1, wherein q is 0, 1 or 2.

[0225] Embodiment 16a. The compound as described in Embodiment 16, wherein q is 0.

[0226] Embodiment 16b. The compound as described in Embodiment 16, wherein q is 1.

[0227] Embodiment 16c. The compound as described in Embodiment 16, wherein q is 2.

[0228] Embodiment 17. The compound of Formula 1 as described in Embodiment 1, wherein the stereochemistry of the carbon atom with * is as depicted in Formula 1' below (1').

[0229]

[0230] Embodiment 18. The compound of Formula 1 as described in Embodiment 1, wherein the stereochemistry of the carbon atom with * is as depicted in Formula 1" below (1").

[0231]

[0232] Embodiment 19. The compound of formula 1 as described in embodiment 1, which is not wherein A is A-1, X 1 It is CH, X 2 Yes CH, R 1a Yes H, R 1b is H, (R 2 ) n It is 2-Me, R 3a is (1')-Me, (R 3b ) p Yes H, R 4a is Cl and (R 4b ) q is a compound of formula 1 wherein H (ie, compound 40).

[0233] Embodiment 20. The compound of formula 1 as described in embodiment 1, which is not wherein A is A-1, X 1 It is CH, X 2 Yes CH, R 1a Yes H, R 1b It is i-Pro, (R 2 ) n Yes H, R 3a is (1')-Me, (R 3b ) p Yes H, R 4a is Me and (R 4b ) q is a compound of formula 1 wherein H (ie, compound 56).

[0234] Embodiment 21. The compound of formula 1 as described in embodiment 1, which is not wherein A is A-1, X 1 It is CH, X 2 Yes CH, R 1a is CH2c-Hex, R 1b is H, (R 2 ) n Yes H, R 3a is (1')-Me, (R 3b ) p Yes H, R 4a is Cl and (R 4b ) q is a compound of Formula 1 wherein H (ie, Compound 90).

[0235] The embodiments of the present invention (including the above embodiments 1-21 and any other embodiments described herein) can be combined in any manner, and the description of the variables in the embodiments relates not only to the compounds of Formula 1, but also to the starting compounds and intermediate compounds that can be used to prepare the compounds of Formula 1. In addition, the embodiments of the present invention (including the above embodiments 1-12a and any other embodiments described herein) and any combination thereof relate to the compositions and methods of the present invention.

[0236] The combinations of Examples 1-21 are shown below:

[0237] Embodiment X. A compound of formula 1 as described in the Summary of the Invention, wherein

[0238] A is A-1, A-2, A-3, A-4, A-5, A-7, A-8, A-9, A-10, A-11, A-12, or A-13; and

[0239] X 1 and X 2 Independently N or CR 2 .

[0240] Embodiment XX. The compound as described in Embodiment X, wherein

[0241] A is A-1.

[0242] Embodiment A. A compound as described in Embodiment XX, wherein

[0243] X 1 and X 2 Both are CR 2 ;

[0244] R 1a is H, halogen, cyano, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, or C1–C7 haloalkoxy;

[0245] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C3–C5 halocycloalkyl, C2–C4 alkoxyalkyl, C1–C4 alkoxy, or C2–C4 alkoxycarbonyl;

[0246] R 2 are independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 alkylsulfonate, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, or C2–C5 alkoxycarbonyl;

[0247] R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C2–C7 alkylthioalkyl, C2–C7 haloalkylthioalkyl, C2–C5 cyanoalkyl, C1–C4 nitroalkyl, C3–C6 alkylcarbonylalkyl, C2–C6 oxacycloalkyl, C3–C7 cycloalkyloxy, or C3–C6 alkoxycarbonylalkyl;

[0248] R 3b is H or halogen;

[0249] R 4a is H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, or C5–C8 trialkylsilylalkynyl;

[0250] R 4b is H, halogen, cyano, nitro, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 alkoxy, or C1–C4 alkylthio.

[0251] Embodiment A1. The compound as described in Embodiment A, wherein

[0252] R 1ais H, halogen, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C7 haloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkoxy, C4–C7 cycloalkoxyalkyl, or C1–C7 haloalkoxy;

[0253] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0254] R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy;

[0255] R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl;

[0256] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and R 4b It is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy.

[0257] Embodiment A2. The compound as described in Embodiment A1, wherein

[0258] R 1ais H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl;

[0259] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0260] R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy;

[0261] R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl; and

[0262] R 4b is H or halogen.

[0263] Embodiment A3. The compound as described in Embodiment A2, wherein

[0264] R 1a is H, Me, Et, i-Pro, i-Bu, Bu, t-Bu, Br, cyano, c-Bu, c-Pen, c-Hex, CH2OMe, CH2O-i-Pro, CH2CH2OMe, CH2-c-Hex or 3-oxetanyl;

[0265] R 1b is H, Me, i-Pro, CN, CF3, F or Cl.

[0266] R 2 is independently H, OH, CN, OEt, propargyl, allyl, c-Pro, F, Cl, Br, CN, Me, Et, OMe, CF3, OCF3 or CH2CF3;

[0267] R 3a is Me, Et, Pro, i-Pro, CF3, CH2F or CH2OMe.

[0268] R 4aIt is H, CN, NO2, F, Cl, Br, Me, Et, CF3, CH2F, OCF3, OMe, CH2OMe, CH=CH2, C≡CSiMe3, C≡CH or c-Pro.

[0269] Embodiment B. A compound as described in Embodiment XX, wherein

[0270] X 1 is N and X 2 Yes CR 2 .

[0271] R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl;

[0272] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0273] R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy;

[0274] R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl;

[0275] R 3b is H or halogen;

[0276] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and

[0277] R 4b is H or halogen.

[0278] Embodiment B1. The compound as described in Embodiment B, wherein

[0279] R1a It is H;

[0280] R 1b It is H;

[0281] R 2 are independently H, C1-C5 alkyl or C1-C5 alkoxy;

[0282] R 3a It is C1–C7 alkyl, C3–C7 cycloalkyl, C1–C7 haloalkyl or C2–C7 alkoxyalkyl.

[0283] R 3b is H or halogen.

[0284] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl.

[0285] R 4b It is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy.

[0286] Embodiment C. The compound as described in Embodiment XX, wherein

[0287] X 1 Yes CR 2 And X 2 is N;

[0288] R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl;

[0289] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0290] R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy;

[0291] R 3ais C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl;

[0292] R 3b is H or halogen;

[0293] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and

[0294] R 4b is H or halogen.

[0295] Specific embodiments include compounds of Formula 1 selected from the group consisting of:

[0296] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methyl-5-[3-(1-methylethyl

[0297]

[0147] -1H-1,2,4-triazol-1-yl]phenyl]methanone (Compound 73);

[0298] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-[3-(1,1-dimethylethyl

[0299]

[0147] -1H-1,2,4-triazol-1-yl]-2-methylphenyl]methanone (Compound 76);

[0300] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methoxy-5-[3-(1-methylethyl

[0301]

[0147] -1H-1,2,4-triazol-1-yl]phenyl]methanone (Compound 84);

[0302] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-(3-ethyl-1H-1,2,4-triazol-1-yl)-2-methoxyphenyl]methanone (Compound 88);

[0303] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-ethyl-5-[3-(1-methylethyl

[0304]

[0147] -1H-1,2,4-triazol-1-yl]phenyl]methanone (Compound 94);

[0305] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)-2-methylphenyl]methanone (Compound 96);

[0306] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 93);

[0307] [(2S)-2,3-Dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl][2-methoxy-5-(1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 63);

[0308] Embodiment S. A compound of formula 1 as described in the Summary of the Invention, wherein

[0309] A is selected from

[0310]

[0311]

[0312]

[0313] Embodiment S1. The compound as described in Embodiment S, wherein

[0314] A is A-1, A-4, A-5, A-12, A-14, A-15 or A-17.

[0315] Embodiment S2. The compound as described in Embodiment S, wherein

[0316] A is A-1.

[0317] Embodiment S3. The compound as described in Embodiment S2, wherein

[0318] X 1 and X 2 Both are CR 2 ;

[0319] R 1ais H, halogen, cyano, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl , C3–C7 oxacycloalkylalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkoxy, C4–C7 cycloalkoxyalkyl, or C1–C7 haloalkoxy;

[0320] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C3–C5 halocycloalkyl, C2–C4 alkoxyalkyl, C1–C4 alkoxy, or C2–C4 alkoxycarbonyl;

[0321] R 2 are independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 alkylsulfonate, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, or C2–C5 alkoxycarbonyl;

[0322] R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C2–C7 alkylthioalkyl, C2–C7 haloalkylthioalkyl, C2–C5 cyanoalkyl, C1–C4 nitroalkyl, C3–C6 alkylcarbonylalkyl, C2–C6 oxacycloalkyl, C3–C7 cycloalkyloxy, or C3–C6 alkoxycarbonylalkyl;

[0323] R 3b is H or halogen;

[0324] R 4a is H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, or C5–C8 trialkylsilylalkynyl;

[0325] R 4b is H, halogen, cyano, nitro, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 alkoxy, or C1–C4 alkylthio.

[0326] Embodiment S4. The compound as described in Embodiment S3, wherein

[0327] R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, or C1–C7 haloalkoxy;

[0328] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0329] R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy;

[0330] R 3ais halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl;

[0331] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and

[0332] R 4b It is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy.

[0333] Embodiment S5. The compound as described in Embodiment S4, wherein

[0334] R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkyloxyalkyl;

[0335] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0336] R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy;

[0337] R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl; and

[0338] R 4bis H or halogen.

[0339] Embodiment S6. The compound as described in Embodiment S5, wherein

[0340] R 1a is H, Me, Et, i-Pro, i-Bu, Bu, t-Bu, Br, cyano, c-Bu, c-Pen, c-Hex, HOCH2, HOC(Me)2, CH2OMe, CH2O-i-Pro, CH2CH2OMe, CH2-c-Hex or 3-oxetanyl;

[0341] R 1b is H, Me, i-Pro, CN, CF3, F or Cl;

[0342] R 2 is independently H, OH, CN, OEt, propargyl, allyl, c-Pro, F, Cl, Br, CN, Me, Et, OMe, CF3, OCF3 or CH2CF3;

[0343] R 3a is Me, Et, Pro, i-Pro, CF3, CH2F or CH2OMe; and

[0344] R 4a It is H, CN, NO2, F, Cl, Br, Me, Et, CF3, CH2F, OCF3, OMe, CH2OMe, CH=CH2, C≡CSiMe3, C≡CH or c-Pro.

[0345] Embodiment S7. The compound as described in Embodiment S2, wherein

[0346] X 1 is N and X 2 Yes CR 2 .

[0347] R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl;

[0348] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0349] R 2are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy;

[0350] R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl;

[0351] R 3b is H or halogen;

[0352] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and

[0353] R 4b is H or halogen.

[0354] Embodiment S8. The compound as described in Embodiment S7, wherein

[0355] R 1a It is H;

[0356] R 1b It is H;

[0357] R 2 are independently H, C1-C5 alkyl or C1-C5 alkoxy;

[0358] R 3a It is C1–C7 alkyl, C3–C7 cycloalkyl, C1–C7 haloalkyl or C2–C7 alkoxyalkyl.

[0359] R 3b is H or halogen.

[0360] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl.

[0361] R 4b It is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy.

[0362] Embodiment S9. The compound as described in Embodiment S2, wherein

[0363] X 1 Yes CR 2 And X 2 is N;

[0364] R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl;

[0365] R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl;

[0366] R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy;

[0367] R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl;

[0368] R 3b is H or halogen;

[0369] R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and

[0370] R 4b is H or halogen.

[0371] Embodiment S10. The compound as described in Embodiment S2, wherein

[0372] R 2 Together they may form a 5- or 6-membered ring containing up to 2 oxygen atoms as ring members.

[0373] Embodiment S11. Specific embodiments include compounds of formula 1 selected from the group consisting of:

[0374] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methyl-5-[3-(1-methylethyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone;

[0375] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-[3-(1,1-dimethylethyl)-1H-1,2,4-triazol-1-yl]-2-methylphenyl]methanone;

[0376] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methoxy-5-[3-(1-methylethyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone;

[0377] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-(3-ethyl-1H-1,2,4-triazol-1-yl)-2-methoxyphenyl]methanone;

[0378] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-ethyl-5-[3-(1-methylethyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone;

[0379] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)-2-methylphenyl]methanone;

[0380] [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)phenyl]methanone;

[0381] [(2S)-2,3-Dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl][2-methoxy-5-(1H-1,2,4-triazol-1-yl)phenyl]methanone;

[0382]

[0383]

[0384] as well as

[0385]

[0386] The present invention also relates to a method for controlling undesirable vegetation, the method comprising applying to the locus of the vegetation a herbicidally effective amount of a compound of the present invention (e.g., as a composition as described herein). It should be noted that the embodiments related to methods of use are those involving the compounds of the above embodiments. The compounds of the present invention are particularly useful for selectively controlling weeds in crops such as wheat, barley, corn, soybeans, sunflowers, cotton, oilseed vegetables and rice, as well as specialty crops such as sugarcane, citrus, fruit and nut crops.

[0387] Also noteworthy as examples are herbicidal compositions of the invention comprising compounds of the above examples.

[0388] The present invention also includes a herbicidal mixture comprising (a) a compound selected from Formula 1, its N-oxide and salt and (b) at least one additional active ingredient selected from the following: (b1) a photosystem II inhibitor, (b2) an acetohydroxyacid synthase (AHAS) inhibitor, (b3) an acetyl-CoA carboxylase (ACCase) inhibitor, (b4) an auxin mimetic, (b5) a 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase inhibitor, (b6) a photosystem I electron diverter, (b7) a protoporphyrinogen oxidase (PPO) inhibitor, (b8) a glutamine synthetase (GS) inhibitor, (b9) a very long chain fatty acid (VLCFA) elongase inhibitor, (b10) an auxin transport inhibitor, (b11) a phytoene dehydrogenase (PDS) inhibitor, (b12) a 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibitor, (b13) a homogentisate solanyltransferase (homogentisate and chloranil. The invention also provides a kind of herbicide comprising: a) chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil, chloranil-ammonium ...

[0389] "Photosystem II inhibitors" (b1) are B -binding site to the D-1 protein and thereby blocks the flow of electrons from Q A Transfer to Q B Electrons blocked from passing through photosystem II are transferred through a series of reactions to form toxic compounds that damage the cell membrane and cause chloroplast swelling, membrane leakage, and ultimately cell rupture.B - The binding position has three different binding sites: binding site A binds triazines such as atrazine, triazinones such as hexazinone, and uracils such as bromidr, binding site B binds phenylureas such as diuron, and binding site C binds benzothiadiazoles such as bentazon, nitriles such as bromoxynil, and phenylpyridazines such as pyridazine. Examples of photosystem II inhibitors include ametryn, amicarb, atrazine, bentazone, bromid, chlorbromid, chlortoluene, chlorotoluron, chlortoluene, benzyluron, chlorazine, betamethoxam, dichlorvos, oxazolidinone, isopentanol, diuron, sulfathiocarb, fenuron, fluometuron, hexazinone, ioxynil, isoproturon, isoxuron, lenacil, linuron, metamitron, methylbenzenesulfuron, bromothiocarb, methoxythiocarb, metribuzin, chlorothiocarb, chloranil ...

[0390] "AHAS inhibitors" (b2) are compounds that inhibit acetohydroxyacid synthase (AHAS), also known as acetolactate synthase (ALS), and thus kill plants by inhibiting the production of branched aliphatic amino acids such as valine, leucine and isoleucine required for protein synthesis and cell growth. Examples of AHAS inhibitors include amidosulfuron, tetrazosulfuron, benzylsulfuron, bispyribac-sodium, chloranthate, chloranthate, chloranthate, chloranthate, chloranthate, chloranthate, cyprosulfuron, bispyribac, ethametsulfuron, ethoxysulfuron, fluazifop-methyl, fluazifop-methyl, flucarbazine, fluazifop-methyl, flucarbazine, fluazifop-methyl sodium, foramsulfuron, halopersulfuron, imazapic, imazapic, imazapic, methazapic, imazapic, Iodoquin, imazethapyr, pyrazosulfuron-methyl, iodosulfuron-methyl (including sodium salt), iodofensulfuron (2-iodo-N-[[(4-methoxy-6-methyl-1,3,5-triazine-2-yl)amino]carbonyl]benzenesulfonamide), mesosulfuron-methyl, pyrazosulfuron-methyl (3-chloro-4-(5,6-dihydro-5-methyl-1,4,2-dioxazin-3-yl)-N-[[(4 ,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-1-methyl-1H-pyrazole-5-sulfonamide), sulfamethoxazole, metsulfuron, nicosulfuron, oxasulfuron, penoxsulam, fluclorosulfuron, propensulfuron sodium, propazinesulfuron (2-chloro-N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-6-propylimidazo[1,2-b]pyridazine-3-sulfonamide), fluclorosulfuron, pyrazine Sulfurcarbon, pyrimidine oxime, pyrimidine oxime, pyrimidine oxime, sodium pyrimidine oxime, sulfasulfuron-methyl, sulfasulfuron-methyl, thiocarb-methyl, thifensulfuron-methyl, fluazifop-methyl, fluazifop-methyl (N-[2-[(4,6-dimethoxy-1,3,5-triazine-2-yl)carbonyl]-6-fluorophenyl]-1,1-difluoro-N-methylmethanesulfonamide), bensulfuron-methyl, bensulfuron-methyl, trifloxysulfuron (including sodium salt), fluazifop-methyl and trifloxysulfuron-methyl.

[0391] "ACCase inhibitors" (b3) are compounds that inhibit acetyl-CoA carboxylase, an enzyme responsible for catalyzing the early steps in lipid and fatty acid synthesis in plants. Lipids are major components of cell membranes, and without lipids, new cells cannot be generated. Inhibition of acetyl-CoA carboxylase and the subsequent lack of lipid production leads to a loss of cell membrane integrity, especially in actively growing areas such as meristems. Eventually seedling and rhizome growth ceases, and seedling meristems and rhizome shoots begin to die back. Examples of ACCase inhibitors include fenoxam, butyrac, clethodim, clodinafop-butyl, cyhalofop-butyl, diclofodine-butyl, fenoxaprop-butyl, fluazifop-butyl, haloxyfop-butyl, pinoxaden, cypermethrin, cypermethrin, quinazolin, quizalofop-butyl, sethoxydim, dapoxetine and oxadiazon, including resolved forms such as fenoxaprop-butyl, fluazifop-butyl, haloxyfop-butyl and quizalofop-butyl and ester forms such as clodinafop-butyl, cyhalofop-butyl, diclofodine and fenoxaprop-butyl.

[0392] Auxins are plant hormones that regulate the growth of many plant tissues. "Auxin mimetics" (b4) are compounds that mimic the plant growth hormone auxin, thus causing uncontrolled and disordered growth and thus plant death in susceptible species. Examples of auxin mimetics include cyclopentylpyrimidine acid (6-amino-5-chloro-2-cyclopropyl-4-pyrimidinecarboxylic acid) and its methyl and ethyl esters and their sodium and potassium salts, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-2-pyridinecarboxylic acid 2-propynyl-1-yl ester (CAS No. 2251111-17-6), 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-2-pyridinecarboxylic acid cyanomethyl ester (CAS No. 2251111-18-7), aminopyralid, benzyl-ethyl ester, benzylpyrimidine, chlorpyrifos, barnyardgrass, clopyralid, dicamba, 2,4-D, 2,4-DB, dichlorvos acid, fluroxypyr, halauxifen (4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-2-picolinic acid), halauxifen-methyl (methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-2-picolinic acid), MCPA, MCPB, mecoprop, picloram, quinclorac, quinmeclorac, 2,3,6-TBA, triclopyr, and methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoro-2-picolinate.

[0393] "EPSP synthase inhibitors" (b5) are compounds that inhibit the enzyme 5-enol-pyruvylshikimate-3-phosphate synthase, which is involved in the synthesis of aromatic amino acids such as tyrosine, tryptophan and phenylalanine. EPSP inhibitor herbicides are easily absorbed by plant leaves and translocated to growing points in the phloem. Glyphosate is a relatively non-selective post-emergence herbicide belonging to this group. Glyphosate includes esters and salts, such as ammonium salts, isopropylammonium salts, potassium salts, sodium salts (including sesquisodium salts) and trimethylsulfonium salts (alternatively known as glufosinate).

[0394] "Photosystem I electron redirectors" (b6) are compounds that receive electrons from photosystem I and, after several cycles, produce hydroxyl radicals. These radicals are highly reactive and tend to damage unsaturated lipids, including membrane fatty acids and chlorophyll. This destroys cell membrane integrity, making cells and organelles "leaky," leading to rapid leaf wilting and dryness, and ultimately plant death. Examples of this second type of photosynthesis inhibitors include diquat, paraquat, and 1-(2-carboxyethyl)-4-(2-pyrimidinyl)pyridazinium (CAS No. 2285384-11-2).

[0395] "PPO inhibitors" (b7) are compounds which inhibit the enzyme protoporphyrinogen oxidase, which rapidly leads in plants to the formation of highly reactive compounds that damage cell membranes, thereby causing exudation of cell fluid. Examples of PPO inhibitors include acifluorfen-sodium, pyrifos-butyl, bispyribac-butyl, fenpyridin-butyl, fenpyridin-butyl, fenpyridin-butyl, fenpyridin-butyl, 3-[2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl]-4,5-dihydro-5-methyl-5-isoxazolecarboxylic acid ethyl ester (CAS No. 1949837-17-5), fenpyridin-butyl, isopropylpyridin-butyl, fluazifop ... Fluazifop-butyl, cypermethrin, fluazifop-butyl, cypermethrin, pyraclostrobin, saflufenacil, sulfentrazone, thiamethoxam, trifludimoxazin (dihydro-1,5-dimethyl-6-sulfanyl-3-[2,2,7-trifluoro-3,4-dihydro-3-oxo-4-(2-propan-1-yl)-2H-1,4-benzoxazin-6-yl]-1,3,5-triazine-2,4(1H,3H)-dione) and fluazifop-butyl (N-[2-[[2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxy-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl]sulfanyl]-1-oxopropyl]-β-alanine methyl ester).

[0396] "GS inhibitors" (b8) are compounds that inhibit the activity of glutamine synthetase, an enzyme used by plants to convert ammonia to glutamine. As a result, ammonia accumulates and glutamine levels decrease. Plant damage may occur due to the combined effects of ammonia toxicity and deficiencies in other amino acids required for other metabolic processes. GS inhibitors include glufosinate and its esters and salts, such as glufosinate and other glufosinate derivatives, glufosinate P ((2S)-2-amino-4-(hydroxymethylphosphinyl)butyric acid) and bilanaphos.

[0397] "VLCFA elongase inhibitors" (b9) are herbicides with various chemical structures that inhibit elongase. Elongase is one of the enzymes located in or near the chloroplasts that is involved in the biosynthesis of VLCFAs. In plants, very long chain fatty acids are the main components of hydrophobic polymers that prevent desiccation at the leaf surface and provide stability to pollen grains. Such herbicides include acetochlor, alachlor, safamidophos, butachlor, benzophenone, dimethoate, dimethenamid, isoxasulfone (3-[[(2,5-dichloro-4-ethoxyphenyl)methyl]sulfonyl]-4,5-dihydro-5,5-dimethylisoxazole), tetrazopyralid, flufenacet, indole, mefenacet, pyraclostrobin, isopropylamine, naproxenamide, naproxenamide, naproxenamide-M ((2R)-N,N-diethyl-2-(1-naphthyloxy)propionamide), pethoxamid, piperafos, pretilachlor, pyraclostrobin, isopropylamine, pyroxasulfone and methoxyfenacet, including resolved forms such as S-isopropylamine and chloroacetamide and oxyacetamide.

[0398] "Auxin transport inhibitors" (b10) are chemicals that inhibit auxin transport in plants, such as by binding to auxin-carrier proteins. Examples of auxin transport inhibitors include diflufenicol, naphthamide (also known as N-(1-naphthyl)-o-carbamoylbenzoic acid and 2-[(1-naphthylamino)carbonyl]benzoic acid).

[0399] "PDS inhibitors" (b11) are compounds that inhibit the carotenoid biosynthetic pathway at the phytoene desaturase step. Examples of PDS inhibitors include fluazifop, diflufenicol, flupyralid, flufenicol, flurazepam, furazolidone, norflurzon and fluazifop.

[0400] "HPPD inhibitors" (b12) are chemical substances that inhibit the biosynthesis of 4-hydroxy-phenyl-pyruvate dioxygenase synthesis. Examples of HPPD inhibitors include cypermethrin, pyraclostrobin, flupyraclostrobin (4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3-pyridinyl]carbonyl]bicyclo[3.2.1]oct-3-en-2-one), fenquinotrione (2-[[8-chloro-3,4-dihydro-4-(4-methoxyphenyl)-3-oxo-2-quinoxalinyl]carbonyl]-1,3- cyclohexanedione), flusulfuron, triazole, isoxachlor, isoxaflutole, mesotrione, sulfamethoxazole, pyrazol, benzylchlor, sulfamethoxazole, teflon, tampron, tolpyralate (1-[[1-ethyl-4-[3-(2-methoxyethoxy)-2-methyl-4-(methylsulfonyl)benzoyl]-1H-pyrazol-5-yl]oxy]ethyl methyl carbonate), benzylchlor, 5-chloro-3- [(2-hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]-1-(4-methoxyphenyl)-2(1H)-quinoxalinone, 4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-3(2H)-pyridazinone, 4-(4-fluorophenyl)-6-[(2-hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]-2-methyl-1,2,4-triazine-3,5(2H,4H)-dione, 5- [(2-Hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]-2-(3-methoxyphenyl)-3-(3-methoxypropyl)-4(3H)-pyrimidinone, 2-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-3-(methylsulfinyl)-4-(trifluoromethyl)benzamide and 2-methyl-3-(methylsulfonyl)-N-(1-methyl-1H-tetrazol-5-yl)-4-(trifluoromethyl)benzamide.

[0401] "HST (homogeneous solanesyl transferase) inhibitors" (b13) disrupt the ability of plants to convert homogentisate to 2-methyl-6-solanesyl-1,4-benzoquinone, thereby disrupting carotenoid biosynthesis. Examples of HST inhibitors include cyclopyrimorate (6-chloro-3-(2-cyclopropyl-6-methylphenoxy)-4-pyridazinyl 4-morpholinecarboxylate), fluazifop, chlorpyrifos, 3-(2-chloro-3,6-difluorophenyl)-4-hydroxy-1-methyl-1,5-naphthyridin-2(1H)-one, 7-(3,5-dichloro-4-pyridinyl)-5-(2,2-difluoroethyl)-8-hydroxypyrrolo[2,3-b]pyrazin-6(5H)-one and 4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-3(2H)-pyridazinone.

[0402] HST inhibitors also include compounds of formula A and B.

[0403]

[0404] Where R d1 is H, Cl or CF3; R d2 is H, Cl or Br; R d3 is H or Cl; R d4 is H, Cl or CF3; R d5 is CH3, CH2CH3 or CH2CHF2; and R d6 is OH, or -OC(=O)-i-Pr; and R e1 is H, F, Cl, CH3 or CH2CH3; R e2 is H or CF3; R e3 is H, CH3 or CH2CH3; R e4 is H, F or Br; R e5 is Cl, CH3, CF3, OCF3 or CH2CH3; R e6 is H, CH3, CH2CHF2 or C≡CH; R e7 is OH, -OC(=O)Et, -OC(=O)-i-Pr or -OC(=O)-t-Bu; and A e8 It is N or CH.

[0405] "Cellulose biosynthesis inhibitors" (b14) inhibit the biosynthesis of cellulose in certain plants. They are most effective when applied pre-emergence or early post-emergence to young or rapidly growing plants. Examples of cellulose biosynthesis inhibitors include oxacill, dichlobenil, fluazifop, triazine, indole, chlorpyrifos, chloranil ... 2 -[(1R,2S)-2,3-dihydro-2,6-dimethyl-1H-inden-1-yl]-6-(1-fluoroethyl)-1,3,5-triazine-2,4-diamine), isoxadiazine and triazine fluazifop-amid.

[0406] "DHODH (dihydroorotate dehydrogenase) inhibitors" (b15) act by inhibiting the catalysis of the fourth step of pyrimidine biosynthesis in plant systems. Inhibition of pyrimidine biosynthesis leads to cessation of plant growth. Examples of DOHDH inhibitors include tetrafluthria ((3S,4S)-N-(2-fluorophenyl)-1-methyl-2-oxo-4-[3-(trifluoromethyl)phenyl]-3-pyrrolidinecarboxamide) and (3S,4R)-N-(2,3-difluorophenyl)-1-methyl-4-[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]-2-oxo-3-pyrrolidinecarboxamide.

[0407] "Other herbicides" (b16) include herbicides that work through a variety of different modes of action, such as mitotic disruptors (e.g., fenfluramide and fenfluramide), organic arsenic compounds (e.g., DSMA and MSMA), 7,8-dihydrofolate synthase inhibitors, chloroplast isoprenoid synthesis inhibitors, and cell wall biosynthesis inhibitors. Other herbicides include those herbicides that have an unknown mode of action or do not fall into the specific categories listed in (b1) to (b14) or work through a combination of the modes of action listed above. Examples of other herbicides include fenthiocarb, sulfamethoxam, chlorfenapyr, bixlozone, broclozone, bromobutyric acid, cypermethrin, clomazone, benzylpyridinium, chlorfenapyr, dimethoate, dimethoate, epyrifenacil, ethoxybencarb, fluazifop, fluazifop, chlorfenapyr, phosphine, phosphine-ammonium, dazomethuron, chlorfenapyr, triazolam (1-(2,4-dichlorophenyl)-N-(2,4-difluorophenyl)-1,5-dihydro-N-(1- methylethyl)-5-oxo-4H-1,2,4-triazole-4-carboxamide), metamidine, methylthiazol, oleic acid, oxazithromycin, nonanoic acid, barnyardgrass, 2,5-anhydro-3,4-dideoxy-4-[[[(5S)-3-(3,5-difluorophenyl)-5-vinyl-4,5-dihydro-5-isoxazolyl]carbonyl]amino]-threo-pentosonic acid methyl ester (CAS No. 27499989-21-6) and 5-[[(2,6-difluorophenyl)methoxy]methyl]-4,5-dihydro-5-methyl-3-(3-methyl-2-thienyl)isoxazole. "Other herbicides" (b16) also include compounds of formula (b16A)

[0408]

[0409] in

[0410] R 12 is H, C1–C6 alkyl, C1–C6 haloalkyl, or C4–C8 cycloalkyl;

[0411] R 13 is H, C1-C6 alkyl or C1-C6 alkoxy;

[0412] Q 1 is an optionally substituted ring system selected from the group consisting of phenyl, thienyl, pyridyl, benzodioxolyl, naphthyl, naphthalenyl, benzofuranyl, furanyl, benzothienyl and pyrazolyl, wherein when substituted, the ring system is replaced by 1 to 3 R 14 replace;

[0413] Q 2 is an optionally substituted ring system selected from the group consisting of phenyl, pyridyl, benzodioxolyl, pyridinonyl, thiadiazolyl, thiazolyl and oxazolyl, wherein when substituted, the ring system is replaced by 1 to 3 R 15 replace;

[0414] Each R 14 independently halogen, C1–C6 alkyl, C1–C6 haloalkyl, C1–C6 alkoxy, C1–C6 haloalkoxy, C3–C8 cycloalkyl, cyano, C1–C6 alkylthio, C1–C6 alkylsulfinyl, C1–C6 alkylsulfonyl, SF5, NHR 17 ; or optionally 1 to 3 R 16 substituted phenyl; or optionally substituted by 1 to 3 R 16 Substituted pyrazolyl;

[0415] Each R 15 are independently halogen, C1–C6 alkyl, C1–C6 haloalkyl, C1–C6 alkoxy, C1–C6 haloalkoxy, cyano, nitro, C1–C6 alkylthio, C1–C6 alkylsulfinyl, C1–C6 alkylsulfonyl;

[0416] Each R 16 are independently halogen, C1-C6 alkyl or C1-C6 haloalkyl;

[0417] R 17 It is a C1–C4 alkoxycarbonyl group.

[0418] In one embodiment, the "other herbicides" (b16) further include compounds of formula (b16A), preferably R 12 is H or C1-C6 alkyl; more preferably, R 12 is H or methyl. Preferably, R 13 is H. Preferably, Q 1 is a phenyl ring or a pyridyl ring, each ring being surrounded by 1 to 3 R 14 More preferably, Q 1 Is 1 to 2 R 14 Preferably, Q 2 Is 1 to 3 R 15 More preferably, Q 2 Is 1 to 2 R 15 Preferably, each R 14 is independently halogen, C1-C4 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy or C1-C3 haloalkoxy; more preferably, each R 14is independently chlorine, fluorine, bromine, C1-C2 haloalkyl, C1-C2 haloalkoxy or C1-C2 alkoxy. 15 are independently halogen, C1-C4 alkyl, C1-C3 haloalkoxy; more preferably, each R 15 is independently chlorine, fluorine, bromine, C1-C2 haloalkyl, C1-C2 haloalkoxy or C1-C2 alkoxy. Specifically, preferred "other herbicides" (b16) include any one of the following (b16A-1) to (b16A-15):

[0419]

[0420]

[0421]

[0422] "Other herbicides" (b16) also include compounds of formula (b16B)

[0423]

[0424] in

[0425] R 18 is H, C1–C6 alkyl, C1–C6 haloalkyl, or C4–C8 cycloalkyl;

[0426] Each R 19 are independently halogen, C1-C6 haloalkyl or C1-C6 haloalkoxy;

[0427] p is an integer of 0, 1, 2 or 3;

[0428] Each R 20 are independently halogen, C1-C6 haloalkyl or C1-C6 haloalkoxy; and

[0429] q is an integer of 0, 1, 2 or 3.

[0430] In one embodiment, the "other herbicides" (b16) further include compounds of formula (b16B), preferably, R 18 is H, methyl, ethyl or propyl; more preferably, R 18 is H or methyl; most preferably, R 18 is H. Preferably, each R 19 is independently chlorine, fluorine, C1-C3 haloalkyl or C1-C3 haloalkoxy; more preferably, each R 19 R is independently chloro, fluoro, C1 fluoroalkyl (i.e., fluoromethyl, difluoromethyl or trifluoromethyl) or C1 fluoroalkoxy (i.e., trifluoromethoxy, difluoromethoxy or fluoromethoxy).20 is independently chlorine, fluorine, C1 haloalkyl or C1 haloalkoxy; more preferably, each R 20 is independently chlorine, fluorine, C1 fluoroalkyl (i.e., fluoromethyl, difluoromethyl or trifluoromethyl) or C1 fluoroalkoxy (i.e., trifluoromethoxy, difluoromethoxy or fluoromethoxy). Specifically, preferred "other herbicides" (b16) include any one of the following (b16B-1) to (b16B-19):

[0431]

[0432]

[0433]

[0434] In another embodiment, the "other herbicides" (b16) further include a compound of formula (b16C),

[0435]

[0436] Where R 1 is Cl, Br or CN; and R 2 It is C(=O)CH2CH2CF3, CH2CH2CH2CH2CF3 or 3-CHF2-isoxazol-5-yl.

[0437] "Herbicide safeners" (b17) are substances added to herbicide formulations to eliminate or reduce the phytotoxic effects of the herbicide on certain crops. These compounds protect the crop from damage by the herbicide, but generally do not prevent the herbicide from controlling undesirable vegetation. Examples of herbicide safeners include, but are not limited to, fenthiocarb, fenthiocarb, benthiocarb, fenthiocarb, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane, cyclohexane 4660), 2,2-dichloro-1-(2,2,5-trimethyl-3-oxazolidinyl)-ethanone and 2-methoxy-N-[[4-[[(methylamino)carbonyl]amino]phenyl]sulfonyl]-benzamide.

[0438] Preferred for better control of undesirable vegetation (e.g., lower application rates such as from greater than additive effects, wider weed control, or enhanced crop safety) or for preventing the development of resistant weeds are mixtures of the compounds of the invention with a herbicide selected from the group consisting of: 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-2-pyridinecarboxylic acid 2-propyn-1-yl ester (CAS No. 2251111-17-6), 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-2-pyridinecarboxylic acid 2-propyn-1-yl ester (CAS No. 2251111-17-6), 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-2-pyridinecarboxylic acid 2-propyn-1-yl ester (CAS No. 2251111-17-6), )-2-pyridinecarboxylic acid cyanomethyl ester (CAS No. 2251111-18-7), 2,5-anhydro-3,4-dideoxy-4-[[[(5S)-3-(3,5-difluorophenyl)-5-vinyl-4,5-dihydro-5-isoxazolyl]carbonyl]amino]-threo-pentosonic acid methyl ester (CAS No. 27499989-21-6), atrazine, tetrazolylsulfuron, flubutyric acid amide, flubutyric acid amide, dichloroisothiazol, bromothiazol, benzisothiazolinone, 1-(2-carboxyethyl)-4-(2-pyrimidinyl)pyridazinium ( CAS No. 2285384-11-2) and its salts, carfentrazone-butyl, chlorimuron-ethyl, 3-[2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl]-4,5-dihydro-5-methyl-5-isoxazolecarboxylic acid ethyl ester (CAS No. 1949837-17-5), chlorsulfuron-ethyl, clomazone, clopyralid potassium, clomiphenesulfonamide, 2-[(2,4-dichlorophenyl)methyl]-4,4-dimethyl-isoxazolidinone, 2-[(2,5-dichloro [(2-hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]-2-methyl-1,2,4-triazine-3,5-(2H,4H)-dione, fluazifop-methyl, flumethoxam, fomesulfuron-methyl, fomesulfuron-butyl, imazethapyr, cypermethrin, mesotrione, metsulfuron-methyl, pethozone, amiloride, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole, sulfamethoxazole and sulfamethoxazole.

[0439] One or more of the following methods and variations as described in Schemes 1-16 can be used to prepare compounds of Formula 1. Unless otherwise indicated, A, R 1a , R 1b , R 2 , R 3a , R 3b , R 4a , R 4b , X 1 , X 2, n, p and q are defined as above in the Summary of the Invention. Compounds of Formulas 1a, 1b, 1c, 1d, 8a, 8b, 10a, 16a and 16b are various subsets of compounds of Formulas 1, 8, 10 and 16; and all substituents for Formulas 1a, 1b, 1c, 1d, 8a, 8b, 10a, 16a and 16b are defined as above for Formula 1, unless otherwise indicated in the present disclosure including these schemes.

[0440] As shown in Scheme 1, compounds of Formula 1a (i.e., compounds of Formula 1, wherein Y is S) can be prepared by treating compounds of Formula 1b (i.e., compounds of Formula 1, wherein Y is O) with a thionating reagent such as Lawesson's reagent, phosphorus decasulfide or phosphorus pentasulfide in a suitable solvent (e.g., tetrahydrofuran or toluene) at a temperature typically from 0°C to the reflux temperature of the solvent.

[0441] Solution 1

[0442]

[0443] Compounds of formula 1b (i.e., compounds of formula 1, wherein Y is O) can be prepared using standard cross-coupling reactions, such as those described in Science of Synthesis: Cross Coupling and Heck-Type Reactions 1, Molander, GA (Volume Editor), Thieme (2013) and Science of Synthesis: Cross Coupling and Heck-Type Reactions 2, Wolfe, JP (Volume Editor), Thieme (2013); and references cited therein. For example, compounds of formula 1c (i.e., Formula 1b, wherein A is bonded through a nitrogen ring member) can be prepared by compounds of formula 2 (wherein Z is a halogen or pseudohalogen, such as Cl, Br, I or OTf) via palladium or copper-mediated coupling with a heterocycle of formula 3 (wherein H is attached to the nitrogen ring member of A), as shown in Scheme 2. Ullmann type coupling conditions, such as those described in J. Org. Chem. 2004, 69, 5578-5587, are generally suitable and are typically catalyzed by a copper salt such as copper(I) iodide or copper(I) oxide and a ligand such as trans-N,N′-dimethylcyclohexane-1,2-diamine, trans-1,2-diaminocyclohexane, N,N′-dimethylethylenediamine, 1,10-phenanthroline, 8-quinolinol, (S)-proline or 2-picolinic acid in the presence of a base (potassium carbonate, cesium carbonate or potassium phosphate) in a suitable solvent (e.g., N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, toluene, 1,4-dioxane or acetonitrile). Temperatures between ambient temperature and 150° C. are generally suitable for the reaction. Palladium catalyzed coupling conditions may also be suitable for some heterocycles. Suitable palladium catalysts include, but are not limited to, tetrakis(triphenylphosphine)palladium(0), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), bis(triphenylphosphine)dichloropalladium(II), palladium(II) acetate, or tris(dibenzylideneacetone)dipalladium(0).In some cases, the addition of a ligand is beneficial, including but not limited to 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), 2-(di-tert-butylphosphino)biphenyl (JohnPhos), 2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl (RuPhos), or 2-di-tert-butylphosphino-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (Me4t-ButylXphos). These reactions are typically carried out with a base such as sodium tert-butoxide, lithium bis(trimethylsilyl)amide, cesium carbonate, potassium carbonate or tripotassium phosphate and a solvent such as tetrahydrofuran, 1,4-dioxane, toluene or tert-butanol at temperatures typically ranging from ambient to 150°C. For a review of these methods, see: Chem. Rev. 2008, 108, 3054-3131; Chem. Sci. 2010, 1, 13-31; Beilstein J. Org. Chem. 2011, 7, 59-74; Chem. Rev. 2016, 116, 12564-12649; and Angew. Chem. Int. Ed. 2017, 56, 16136-16179 and Tetrahedron 2019, 75, 4199-4211. Those skilled in the art will recognize that when more than one nitrogen atom is present in the heterocycle of Formula 3, regioisomers may form and that standard purification methods such as chromatography can generally be used to separate the mixture. The heterocycles of Formula 3 are generally commercially available or known in the literature.

[0444] Alternatively, when the aryl ring is sufficiently activated, for example when X 1 is N or when R 2When it is an appropriately positioned electron-withdrawing group, a compound of formula 1c can generally be prepared without the addition of a metal catalyst. This is achieved by reacting a compound of formula 2 (wherein Z is a halogen such as F or Cl) with a heterocycle of formula 3 in the presence of a base (e.g., potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, sodium hydroxide, potassium tert-butoxide, sodium hydride or potassium hydride) in an appropriate solvent (e.g., N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, diethylene glycol dimethyl ether, acetonitrile or toluene). Temperatures ranging from 0°C to 200°C are generally suitable for the reaction. For examples of this reaction in the literature, see: WO 2012 / 054510; WO 2020 / 207941 and J.Med.Chem [Journal of Pharmaceutical Chemistry]. 2014, 57, 10013-10030.

[0445] In some cases, compounds of Formula 1c can be more easily obtained using standard heterocyclic synthesis procedures known to those skilled in the art. For suitable methods, see Science of Synthesis, Vol. 12-13, Neier, R., Storr, RC and Gilchrist, TL (Vol. Editors), Thieme (2002-2003); Comprehensive Heterocyclic Chemistry IV, Vol. 4-6, Black, DS, Cossy, J. and Stevens, CV (Editors), Elsevier (2022); WO 2015 / 160636 and WO2017 / 205709; and references cited therein.

[0446] Solution 2

[0447]

[0448] As shown in Scheme 3, compounds of Formula 1d (i.e., compounds of Formula 1b, wherein A is bonded through a carbon ring member) can be prepared by well-known metal-catalyzed cross-linking reactions between a heterocycle of Formula 4 (wherein Z is a halogen or pseudohalogen such as Cl, Br, I or OTf and is attached to a carbon ring member) and an organometallic compound of Formula 5 (wherein M is a transmetallating group) (such as, but not limited to, boronic acids (e.g., M is B(OH)2), boric acid esters (e.g., M is B(-O(CMe2)2O-) or organotin reagents (e.g., M is Sn(n-Bu)3, SnMe3)). The metal catalysts used in these couplings include, but are not limited to, tetrakis(triphenylphosphine)palladium(0), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), bis(triphenylphosphine)dichloropalladium(II), palladium(II) acetate or tris(dibenzylideneacetone)dipalladium(0). In some cases Under the condition of , the addition of ligands is beneficial, including but not limited to 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), tricyclohexylphosphine or tri(2-furyl)phosphine. Typically, these reactions are carried out in solvents such as N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, toluene, 1,2-dimethoxyethane, 1,4-dioxane, tetrahydrofuran, acetonitrile or ethanol and temperatures generally ranging from ambient temperature to 150°C. Those skilled in the art will recognize that the reaction conditions will depend on the organometallic substance used in the reaction, for example, when the compound of Formula 5 is a boron reagent, a base is required, typically an aqueous base. Suitable bases include potassium carbonate, sodium carbonate, cesium carbonate, sodium bicarbonate or potassium phosphate. When the compound of Formula 5 is a tin reagent, no base is required.For a review of transition metal-catalyzed cross-coupling reactions, see: E. Negishi, Handbook of Organopalladium Chemistry for Organic Synthesis, John Wiley and Sons, Inc., New York, 2002; N. Miyaura, Cross-Coupling Reactions: A Practical Guide, Springer, New York, 2002; HC Brown et al., Organic Synthesis via Boranes, Vol. 3, Aldrich Chemical Co., Milwaukee, WI, 2002; Suzuki et al., Chem. Rev. 1995, 95, 2457-2483 and Molander et al., Acc. Chem. Res. 2007, 40, 275-286. And Chem. Soc. Rev. 2013, 42, 5270. For relevant examples of reactions using boron reagents in the literature, see: WO 2012 / 137982, WO 2015 / 017610, WO 2016 / 040223 and WO 2020 / 182990. For relevant examples of reactions using tin reagents in the literature, see: WO 2019 / 195810 and WO 2021 / 242677. Heterocycles of formula 4 are generally commercially available or known in the literature.

[0449] Solution 3

[0450]

[0451] Those skilled in the art will recognize that in some cases, due to the availability or stability of the required reagents, it may be beneficial to reverse the polarity of the coupling partner, as shown in Scheme 4. In this case, a heterocycle of formula 6 (wherein M is a transmetallation group such as, but not limited to, B(OH)2, B(-O(CMe2)2O-), BF3K, Sn(n-Bu)3 or SnMe3 or ZnBr, and is attached to a carbon ring member) is coupled with a compound of formula 2 (wherein Z is a halogen or pseudohalogen, such as Cl, Br, I or OTf). For relevant examples in the literature, see: WO 2012 / 063207 and WO 2019 / 162323. For examples of cross-coupling of (hetero)aryl halides with alkyl coupling partners, see: Chem. Rev. 2011, 111, 1417-1492; ACS Med. Chem. Lett. 2020, 11, 597-604 and J. Org. Chem. 2021, 86, 10380-10396; and references cited therein. The heterocycles of formula 6 are generally commercially available or known in the literature.

[0452] In some cases, compounds of Formula 1d can be more readily obtained using standard heterocyclic synthesis procedures known to those skilled in the art. For suitable methods, see Science of Synthesis, Volumes 11-13 and 15, Schaumann, E., Neier, R., Storr, RC; Gilchrist, TL and Black, DS (Volume Editors), Thieme (2001-2004) and Comprehensive Heterocyclic Chemistry IV, Volumes 4-7, Black, DS, Cossy, J. and Stevens, CV (Editors), Elsevier (2022); and references cited therein.

[0453] Solution 4

[0454]

[0455] As shown in Scheme 5, organometallic compounds of Formula 5 (wherein M is a transmetalating group such as, but not limited to, B(-O(CMe2)2O-), Sn(n-Bu)3, or SnMe3) can be prepared from compounds of Formula 2 (wherein Z is a halogen or pseudohalogen, such as Cl, Br, I, or OTf) using well-known metal-catalyzed cross-coupling reactions. For example, pinacol boronates (wherein M = B(-O(CMe2)2O-) can generally be prepared using palladium-catalyzed borylation conditions such as those described in J. Org. Chem. 1995, 60, 7508-7510 and J. Org. Chem. 2021, 86, 103-109; and references cited therein. In the presence of a palladium catalyst such as [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride and a base such as potassium acetate, in a solvent such as The compound of formula 2 is treated with bis(pinacolato)diboron in dioxane or dimethyl sulfoxide at a temperature ranging from ambient temperature to the reflux temperature of the solvent. Similarly, trialkyltin reagents (e.g., where M = SnMe3, SnBu3) can generally be prepared from compounds of formula 2 by treating with tin alkane such as hexamethylditin or hexabutylditin in the presence of a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0) in a solvent such as dioxane or toluene at a temperature ranging from ambient temperature to the reflux temperature of the solvent. For examples of this reaction in the literature, see: WO 03 / 077918 and WO 2021 / 050964. For additional details on the preparation and use of organoboron and organotin reagents, see Science of Synthesis, Vol. 5-6, Moloney, MG and Kaufmann, DE (Vol. Edited), Thieme (2002-2004); and references cited therein.

[0456] Solution 5

[0457]

[0458] As shown in Scheme 6, compounds of Formula 1 or 2 can be prepared by reacting a carboxylic acid of Formula 7 with a benzoxazine of Formula 8. The reaction proceeds via activation of the carboxylic acid of Formula 7 followed by reaction with the benzoxazine of Formula 8. The carboxylic acid can be activated with a coupling reagent or by converting the carboxylic acid into an acyl halide such as an acyl chloride. For example, compounds of Formula 7 and 8 can be reacted in the presence of a coupling reagent such as propylphosphonic anhydride (T3P), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC), 1,1′-carbonyldiimidazole (CDI), or 2-chloro-1-methylpyridinium iodide (Mukaiyama's reagent). Polymer-supported reagents, such as polymer-supported cyclohexylcarbodiimide, are also suitable. These reactions are typically carried out in a suitable solvent (e.g., dichloromethane, 1,2-dichloroethane, ethyl acetate, acetonitrile or N,N-dimethylformamide) in the presence of a base (e.g., triethylamine, N,N-diisopropylethylamine or pyridine), optionally with a catalytic amount of 4-(dimethylamino)pyridine, at a temperature ranging from 0°C to the reflux temperature of the solvent. Alternatively, the carboxylic acid of formula 7 can be converted to the acid chloride by treatment with a reagent such as thionyl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus trichloride or phosphorus pentachloride neat or in a suitable solvent (e.g., dichloromethane, 1,2-dichloroethane or toluene) and optionally with a catalytic amount of N,N-dimethylformamide at a temperature ranging from 0°C to the reflux temperature of the solvent. The subsequent reaction of the acid chloride with the benzoxazine of formula 8 is generally carried out in the presence of a base such as triethylamine, N,N-diisopropylethylamine or pyridine, optionally with a catalytic amount of 4-(dimethylamino)pyridine, in a suitable solvent such as tetrahydrofuran, dioxane, toluene, dichloromethane, chloroform, 1,2-dichloroethane or ethyl acetate, at a temperature ranging from 0°C to the reflux temperature of the solvent. For relevant examples of this reaction in the literature, see: J. Med. Chem. [Journal of Medicinal Chemistry] 2012, 55, 10475-10489; WO 2010 / 049302 and WO 2016 / 001631. The carboxylic acids of formula 7 are generally commercially available or known in the literature. In some cases, the corresponding acid chlorides are also commercially available.

[0459] Solution 6

[0460]

[0461] Several methods are well known in the literature for preparing benzoxazines of formula 8. In addition, some benzoxazines of formula 8 are commercially available. By treating a benzoxazinone of formula 10 (wherein R bis H or a suitable protecting group such as Bn or p-methoxybenzyl and p is 0 or 1), the preparation of benzoxazines of Formula 8a (i.e., compounds of Formula 8, wherein R b is H and p is 0 or 1) or 9 (where R b is a suitable protecting group such as Bn or p-methoxybenzyl and p is 0 or 1). For relevant examples of this reaction in the literature, see WO 2015 / 095795. Some benzoxazinones of formula 10 are commercially available or known in the literature.

[0462] Solution 7

[0463]

[0464] As shown in Scheme 8, a benzoxazine of Formula 8b (ie, a compound of Formula 8, wherein R b is H, and R in the α-position of the N atom 3b is F and p is 2 or 3) or 11 (where R b is a suitable protecting group such as Bn or p-methoxybenzyl, and R at the α-position of the N atom is 3b is F and p is 2 or 3) can be obtained by benzoxazinone of formula 10 (wherein R b is H or a suitable protecting group such as Bn or p-methoxybenzyl and p is 0 or 1) can be prepared by fluorination. For example, α,α-difluoroamine can be prepared by first chlorinating the amide with a reagent such as oxalyl chloride in a suitable solvent (e.g., dichloromethane, carbon tetrachloride, tert-butyl methyl ether or cyclopentyl methyl ether) at a temperature generally between 0°C and the reflux temperature of the solvent. It is then fluorinated with a reagent such as sodium fluoride, potassium fluoride or triethylamine trihydrofluoride in a suitable solvent (e.g., acetonitrile, dichloromethane or 1,3-dimethyl-2-imidazolidinone) at a temperature generally between 0°C and the reflux temperature of the solvent. Alternatively, the amide can first be converted to a thioamide by treatment with a sulfiding reagent such as Lawesson's reagent or phosphorus pentasulfide in a suitable solvent (e.g., toluene, xylene, dioxane or tetrahydrofuran) at a temperature between ambient temperature and the reflux temperature of the solvent. In a second step, a reagent such as bis(2-methoxyethyl)aminosulfur trifluoride can be used. Fluorination is carried out in a suitable solvent such as dichloromethane, optionally in the presence of a Lewis acid catalyst such as antimony (III) chloride, at a temperature generally between 0° C. and ambient temperature. For relevant examples of this reaction in the literature, see: EP 1437342; WO 2006 / 049014; Tetrahedron, 2013, 69, 8943-8951 and ChemMedChem, 2013, 8, 779-799; and references cited therein.

[0466] Solution 8

[0467]

[0468] As shown in Scheme 9, a benzoxazinone of Formula 10a (ie, a compound of Formula 10, wherein R b is H) can be obtained by a compound of formula 12 (wherein R a C1-C4 alkyl, typically methyl or ethyl) is prepared by nitro reduction followed by cyclization during reduction or when heated. The reaction is easily achieved under a series of conditions, such as iron metal in the presence of an acid such as acetic acid, hydrochloric acid or aqueous ammonium chloride, optionally with a solvent such as methanol, ethanol, ethyl acetate or N,N-dimethylformamide at a temperature ranging from ambient temperature to the reflux temperature of the solvent. Other suitable conditions include zinc metal and acetic acid or aqueous ammonium chloride, and stannous chloride in aqueous hydrochloric acid or ethanol. Alternatively, the reaction can use a transition metal catalyst, such as palladium / carbon, platinum oxide or Raney nickel, under a hydrogen atmosphere, in a suitable solvent (e.g. methanol, ethanol, ethyl acetate or tetrahydrofuran). The temperature typically ranges from ambient temperature to 80 ° C. The reaction can usually be carried out in a Parr hydrogenator. For relevant examples of this reaction in the literature, see: WO 2015 / 095795 and Angew. Chem. Int. Ed. [German Angewandte Chemie] 2014, 53, 6126-6130.

[0469] Solution 9

[0470]

[0471] As shown in Scheme 10, the compound of Formula 12 can be prepared by reacting a nitrophenol of Formula 13 with an α-hydroxy ester of Formula 14 (where R a is a C1-C4 alkyl group, typically methyl or ethyl). Typical reaction conditions include triphenylphosphine and an azodicarboxylate, such as diethyl azodicarboxylate or diisopropyl azodicarboxylate, in a solvent such as tetrahydrofuran or dichloromethane at a temperature ranging from about -10°C to the reflux temperature of the solvent. Alternatively, compounds of formula 12 can be prepared by reacting a nitrophenol of formula 13 with an α-haloester of formula 15 (wherein LG is a leaving group, such as Cl or Br, and R ais C1-C4 alkyl, typically methyl or ethyl) in the presence of a base such as potassium carbonate or cesium carbonate, in a solvent such as N,N-dimethylformamide, acetone or 1,4-dioxane, at a temperature typically ranging from 0°C to the reflux temperature of the solvent. For relevant examples of these reactions in the literature, see: Bioorg.Med.Chem. [Biological Organic and Medicinal Chemistry] 2013, 23, 4501-4505; Bioorg.Med.Chem. [Biological Organic and Medicinal Chemistry] 2007, 15, 5912-5949 and WO 2017 / 205536. Nitrophenols, α-hydroxy esters and α-haloesters of formula 13, 14 and 15 are generally commercially available or known in the literature.

[0472] Solution 10

[0473]

[0474] Alternatively, benzoxazines of formula 8 can be prepared according to the following sequence. As shown in Scheme 11, β-amino alcohols of formula 16 (wherein R b is H or a suitable protecting group such as Ts or Bn, and X is a halogen or pseudohalogen such as F, Cl, Br, I or OTs) can be prepared by the ring opening of the epoxide of formula 18 by nucleophilic attack by the aniline of formula 17. The reaction can generally be achieved by heating the aniline and epoxide neat or in a suitable solvent (e.g., ethanol or N,N-dimethylformamide) at a temperature generally ranging from 40°C to 180°C. Optionally, a base (e.g., potassium carbonate or sodium hydride), a Lewis acid (e.g., ytterbium (III) trifluoromethanesulfonate or lithium bromide) or a phase transfer catalyst (e.g., benzyltriethylammonium chloride or tetrabutylammonium bromide) can be added to promote the reaction. Those skilled in the art will recognize that the epoxide substituents and reaction conditions affect the regioselectivity of the reaction, for example, acidic conditions can reverse the regioselectivity of the epoxide ring opening. For relevant examples of these reactions in the literature, see: Ind. Eng. Chem. Res. [Industrial and Engineering Chemistry Research] 2003, 42, 680-686; Eur. J. Org. Chem. [European Journal of Organic Chemistry] 2004, 3597-3600; J. Het. Chem. [Journal of Heterocyclic Chemistry] 2010, 47, 1406-1410 and WO 2015 / 095792; and references cited therein. Anilines and epoxides of formula 17 and formula 18 are generally commercially available or known in the literature.

[0475] Solution 11

[0476]

[0477] As shown in Scheme 12, the N-tosyl protected benzoxazines of Formula 20 can be prepared from β-amino alcohols of Formula 16a (i.e., compounds of Formula 16, wherein R b is Ts and X is typically F but in some cases is OTs) by treating with a base such as, but not limited to, sodium hydroxide, potassium tert-butoxide or sodium hydride, optionally in the presence of a phase transfer catalyst such as tetrabutylammonium bromide, typically in a solvent such as tetrahydrofuran, at a temperature ranging from ambient temperature to the reflux temperature of the solvent. For examples of this reaction in the literature, see: Ind. Eng. Chem. Res. [Industrial and Engineering Chemistry Research] 2003, 42, 680-686; WO 2015 / 095792 and J. Mol. Catal. A Chem. [Molecular Catalysis Journal A: Chemistry] 2008, 288, 28-32. Benzoxazines of formula 8 can be prepared by removing the N-tosyl protecting group. This can be achieved under reducing conditions, for example, by treating with magnesium metal in methanol at a temperature ranging from 0° C. to the reflux temperature of the solvent, optionally with ultrasonic treatment. Alternatively, the reaction can be achieved using acidic hydrolysis conditions, for example, treatment with sulfuric acid, neat or in a solvent such as dichloromethane, at a temperature typically ranging from 0°C to the reflux temperature of the solvent. For relevant examples of these reactions in the literature, see: Chem. Commun. 1999, 2095-2096; WO 2015 / 095792 and J. Org. Chem. 2021, 86, 16573-16581; and references cited therein.

[0478] Solution 12

[0479]

[0480] Alternatively, as shown in Scheme 13, Formula 8 (wherein R b is H) or 21 (where R b is a suitable protecting group, such as Ts or Bn) can be prepared from a β-amino alcohol of Formula 16b (i.e., a compound of Formula 16, wherein R bis H or a suitable protecting group and X is a halogen such as Cl, Br or I) by transition metal catalyzed O-arylation. The reaction can be catalyzed by copper salts such as copper (I) iodide and ligands such as 1,10-phenanthroline, or by palladium salts or complexes such as palladium (II) acetate or tris (dibenzylideneacetone) dipalladium (0) and phosphine ligands such as 2-di-tert-butylphosphino-2'-(N,N-dimethylamino)biphenyl (t-BuDavePhos) or racemic-2-(di-tert-butylphosphino)-1,1'-binaphthyl (TrixiePhos). These reactions are carried out in a solvent such as dioxane or toluene in the presence of a base such as sodium tert-butoxide, cesium carbonate or potassium phosphate at a temperature generally ranging from ambient temperature to the reflux temperature of the solvent. For examples of this reaction in the literature, see: J. Am. Chem. Soc. 2000, 122, 12907-12908; J. Am. Chem. Soc. 2001, 123, 12202-12206; J. Mol. Catal. A Chem. 2008, 288, 28-32 and Tetrahedron Lett. 2009, 50, 3790-3793. Where a protecting group is utilized, removal using standard procedures known to those skilled in the art provides benzoxazines of formula 8.

[0481] Solution 13

[0482]

[0483] In some cases, benzoxazines of formula 8 can be more easily obtained according to the sequence shown in scheme 14. Compounds of formula 22 can be prepared by the ring opening of epoxides of formula 18 by nucleophilic attack of phenols of formula 13. The reaction can generally be carried out in the presence of a base (e.g., monosodium phosphate, sodium phosphate, potassium carbonate, sodium hydride, sodium hydroxide, cesium fluoride or 1,8-diazabicyclo[5.4.0]undec-7-ene) in a suitable solvent (e.g., acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, dichloromethane, toluene, methanol, isopropanol and / or water) at a temperature generally ranging from ambient temperature to 180°C. Lewis acids (e.g., zinc chloride or boron trifluoride etherate) can also be used to promote the reaction. Those skilled in the art will recognize that the epoxide substituents and reaction conditions affect the regioselectivity of the reaction, for example, acidic conditions can reverse the regioselectivity of the epoxide ring opening. For relevant examples of this reaction in the literature, see: WO 2000 / 010994; US2007 / 0185097A1; WO 2009 / 009501; J.Med.Chem. [Journal of Medicinal Chemistry] 2023, 66, 1583-1600 and Angew.Chem.Int.Ed. [German Applied Chemistry] 2023, 62, e202217064. Subsequently, compounds of formula 23 can be prepared by nitro reduction, which can be achieved using standard conditions as previously described (see Scheme 9), such as palladium / carbon in a suitable solvent such as methanol under a hydrogen atmosphere. For relevant examples of this reaction in the literature, see: WO 2009 / 009501, WO 2010 / 047956 and WO 2019 / 162323. Benzoxazine of formula 8 can be prepared by treating with an acid (e.g., phosphoric acid or p-toluenesulfonic acid) in a suitable solvent (e.g., xylene or toluene) of formula 23 at a temperature generally ranging from ambient temperature to the reflux temperature of the solvent. For relevant examples of this reaction in the literature, see: WO 2017 / 108723 and Synth. Commun. [Synthetic Communications] 1998, 28, 4105-4121. In some cases, it may be beneficial to convert an alcohol into a leaving group (e.g., Cl or OMs) to promote the reaction, which may then be carried out in the presence of a base (e.g., potassium carbonate) in a suitable solvent (e.g., N,N-dimethylformamide) at a temperature ranging from ambient temperature to the reflux temperature of the solvent. For relevant examples of this reaction in the literature, see: WO 2002 / 070726. Alternatively, in some cases, use of an appropriate aniline protecting group (eg, tosyl) enables ring closure using Mitsunobu conditions as previously described (see Scheme 10), such as triphenylphosphine and diethyl azodicarboxylate in a suitable solvent such as tetrahydrofuran.For relevant examples of this reaction in the literature, see: Org. Biomol. Chem. 2010, 8, 2823-2828 and J. Org. Chem. 2015, 80, 3815-3824.

[0484] Solution 14

[0485]

[0486] As shown in Scheme 15, the benzoxazine of Formula 8c (i.e., the compound of Formula 8, wherein one R at the α-position of the NH 3b (i.e. α-amino R 3b ) is R c And the remaining α-amino R 3b It is H; R c is H or C1-C3 alkyl; or R c Can be used with R 3a or α-oxo R 3b together to form a ring) can be made from a compound of formula 24 (wherein R c is H or C1-C3 alkyl; or R c Can be used with R 3a or R 3bTogether to form a ring) is prepared by nitro reduction followed by reductive amination. The reaction can use a transition metal catalyst, such as but not limited to palladium / carbon, platinum / carbon or Raney nickel, under a hydrogen atmosphere, in a suitable solvent (e.g. methanol, ethanol, isopropanol, ethyl acetate, toluene or tetrahydrofuran). The temperature typically ranges from ambient temperature to 80 ° C. The reaction can usually be carried out in a Parr hydrogenator, optionally under atmospheric pressure. Alternatively, the reaction can be achieved in a stepwise manner. Nitro reduction can be achieved under a range of conditions, such as iron metal in the presence of an acid such as acetic acid, hydrochloric acid or aqueous ammonium chloride, optionally with a solvent such as methanol, ethanol, ethyl acetate, tetrahydrofuran or N, N-dimethylformamide at a temperature ranging from ambient temperature to the reflux temperature of the solvent. Other suitable conditions include zinc metal and acetic acid or aqueous ammonium chloride, and stannous chloride in aqueous hydrochloric acid or ethanol. The second step involves the reduction of the imine, which can be achieved using a reducing agent such as sodium borohydride, sodium cyanoborohydride or lithium aluminum hydride in a suitable solvent (e.g., ethanol, methanol, tetrahydrofuran or dichloromethane, optionally with a co-solvent or additive such as water or acetic acid) at a temperature typically between -78°C and the reflux temperature of the solvent. Other suitable reducing conditions for this step include, but are not limited to, hydrogen and palladium / carbon in a solvent such as methanol, or in triethylsilane and trifluoroacetic acid in a solvent such as dichloromethane. For relevant examples of this reaction in the literature, see: J. Org. Chem. [Journal of Organic Chemistry] 2002, 67, 6097-6103; WO 2014 / 171527; J. Org. Chem. [Journal of Organic Chemistry] 2015, 80, 3815-3824; WO 2015 / 124868; WO 2017 / 172505 and WO 2022 / 035799.

[0487] Solution 15

[0488]

[0489] As shown in Scheme 16, the compound of Formula 24 can be prepared by reacting a nitrophenol of Formula 13 with a compound of Formula 26 (wherein LG is a leaving group such as Cl or Br, and R c is H or C1-C3 alkyl; or R c Can be used with R 3a or R 3b Together to form a ring) in the presence of a base (such as potassium carbonate, cesium carbonate, sodium bicarbonate or sodium hydride) (optionally with an additive such as sodium iodide) in a solvent such as N,N-dimethylformamide, acetone or 1,4-dioxane at a temperature typically ranging from 0°C to the reflux temperature of the solvent. Alternatively, in some cases, by reacting a nitrophenol of formula 13 with a compound of formula 25 (wherein R c is H or C1-C3 alkyl; or Rc Can be used with R 3a or R 3b The reaction of 2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2-(2- In some cases, compounds of Formula 24 may be more readily accessed using a protecting group to mask the carbonyl, such as using an acetal group to mask an aldehyde, or via standard functional group interchange of one carbonyl functionality for another.

[0490] Scheme 16

[0491]

[0492] Those skilled in the art recognize that various functional groups can be converted to others to provide different compounds of Formula 1. For a valuable resource that illustrates the interconversion of functional groups in a simple and direct manner, see Larock, RC, Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd edition, Wiley-VCH, New York, 1999. For example, intermediates used to prepare compounds of Formula 1 may contain aromatic nitro groups, which can be reduced to amino groups and then converted to various halides via reactions well known in the art (such as the Sandmeyer reaction) to provide compounds of Formula 1. In many cases, the above reactions can also be performed in an alternating order.

[0493] It should be recognized that some of the reagents and reaction conditions described above for the compounds of the preparation formula 1 may not be compatible with some functional groups present in the intermediate. In these cases, the protection / deprotection sequence or functional group interconversion combined with the synthesis will help to obtain the desired product. The use and selection of protecting groups will be obvious to those skilled in the art of chemical synthesis (see, for example, Greene, TW; Wuts, PGM Protective Groups in Organic Synthesis [protective groups in organic synthesis], 2nd edition; Wiley Press: New York, 1991). Those skilled in the art will recognize that in some cases, after introducing a given reagent as depicted in any individual scheme, it may be necessary to perform additional conventional synthesis steps not described in detail to complete the synthesis of the compound of formula 1. Those skilled in the art will also recognize that it may be necessary to perform the combination of the steps shown in the above scheme in an order different from the order specifically presented by the compound of the preparation formula 1.

[0494] Those skilled in the art will also recognize that the compounds of Formula 1 and intermediates described herein can be subjected to a variety of electrophilic, nucleophilic, free radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents.

[0495] Without further elaboration, it is believed that those skilled in the art can utilize the present invention to the greatest extent using the previous description. The following non-limiting examples are illustrations of the present invention. The steps in the following examples illustrate the procedures of each step in the overall synthesis transformation, and the starting materials for each step do not have to be prepared by the specific preparation experiments described in other examples or steps by their procedures. Percentages are by weight, except for chromatographic solvent mixtures or otherwise specified. Unless otherwise specified, the number and percentage of chromatographic solvent mixtures are by volume. Unless otherwise specified, all NMR spectra are reported at 500MHz in CDCl3 with a low field from tetramethylsilane, wherein s means a singlet, brs means a wide singlet, d means a doublet, t means a triplet, q means a quartet, p means a quintet and m means a multiplet.

[0496] Synthesis Example 1

[0497] Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[5-(3-isopropyl-1,2,4-triazol-1-yl)-2-methoxy-phenyl]methanone (Compound 84)

[0498] Step A: Preparation of (2S)-2-(2-chloro-6-nitro-phenoxy)propionic acid methyl ester

[0499] ______________________________________________________________

[0500] (R)-(+)-methyl lactate (12.4mL, 130mmol) is added to a stirred mixture of 2-chloro-6-nitro-phenol (15g, 86mmol) and triphenylphosphine (29g, 112mmol) in anhydrous tetrahydrofuran (245mL). The mixture is cooled to 0 ° C, and then a solution of diisopropyl azodicarboxylate (22mL, 112mmol) in anhydrous tetrahydrofuran (25mL) is added over 20min. The reaction mixture is stirred at room temperature overnight and then concentrated. A mixture of hexane and ether (1: 1, 700mL) is added and the mixture is stirred for 2h, resulting in the formation of a precipitate. The mixture is filtered through a diatomaceous earth pad, rinsed with hexane / ether (1: 1, 200mL) and the filtrate is concentrated. The crude material is purified by column chromatography on silica gel (gradient of 10%–25% ethyl acetate in hexane) to obtain the title compound (23g) as a yellow oil.

[0501] 1 H NMR(CDCl3)δ7.71(dd,1H),7.60(dd,1H),7.19–7.16(m,1H),4.93(q,1H),3.71(s,3H),1.69(d,3H).

[0502] Step B: Preparation of (2S)-8-chloro-2-methyl-4H-1,4-benzoxazin-3-one

[0503] _______________________________________________________________

[0504] At 50 ° C, to a stirred solution of (2S)-2-(2-chloro-6-nitro-phenoxy)methyl propionate (i.e., the product of step A) (22g, 86mmol) in ethanol (310mL), a solution of ammonium chloride (9.2g, 173mmol) in water (35mL) was added. Then when the reaction mixture was heated from 50 ° C to 70 ° C, iron powder (14.5g, 259mmol) was added portionwise over 12min. After stirring at 70 ° C for 48h, the mixture was cooled to room temperature and filtered through a diatomaceous earth pad. The filtrate was concentrated, and ethyl acetate and water were then added. Each layer was separated and the aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous ammonium chloride solution, dried over anhydrous magnesium sulfate, filtered through a diatomaceous earth pad and concentrated to provide the title compound (16.6g) as a white solid, which was used without further purification.

[0505] 1 H NMR(CDCl3)δ8.47(br s,1H),7.06(dd,1H),6.91–6.88(m,1H),6.72(dd,1H),4.77(q,1H),1.63(d,3H).

[0506] Step C: Preparation of (2S)-8-chloro-2-methyl-3,4-dihydro-2H-1,4-benzoxazine

[0507] _______________________________________________________________

[0508] At 0 ° C, over 30 min, to a stirred solution of (2S)-8-chloro-2-methyl-4H-1,4-benzoxazine-3-one (i.e., the product of step B) (9.1 g, 46 mmol) in anhydrous tetrahydrofuran (100 mL) was added borane tetrahydrofuran complex (1M, in tetrahydrofuran, 92 mL, 92 mmol). The reaction mixture was stirred at room temperature overnight, then cooled to 0 ° C and methanol (70 mL) was slowly added. After stirring at room temperature for 1 h, the mixture was concentrated and distributed between ethyl acetate and water. The layers were separated, and the organic phase was washed with water, brine, dried over anhydrous magnesium sulfate and concentrated to give the title compound (8.3 g) as a white solid, which was used without further purification.

[0509] 1 H NMR(CDCl3)δ6.73(dd,1H),6.67–6.64(m,1H),6.49(dd,1H),4.34–4.28(m,1H),3.82(br s,1H),3.37(dd,1H),3.13(dd,1H),1.44(d,3H).

[0510] Step D: Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-(5-iodo-2-methoxy-phenyl)methanone

[0511] _______________________________________________________________

[0512] To a stirred solution of (2S)-8-chloro-2-methyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C) (0.7 g, 3.8 mmol), 5-iodo-2-methoxy-benzoic acid (1.06 g, 3.8 mmol) and triethylamine (1.6 mL, 11.4 mmol) in 1,2-dichloroethane (13 mL) was added propylphosphonic anhydride (50 wt.%, in ethyl acetate, 4.9 mL, 8.2 mmol). The mixture was stirred at 70 ° C for 24 h, then cooled to room temperature and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-30% ethyl acetate in hexane). The isolated material was dissolved in ethyl acetate, washed with 1N aqueous hydrochloric acid solution, 1N aqueous sodium hydroxide solution, brine, dried over anhydrous magnesium sulfate, concentrated and then further purified by column chromatography on silica gel (gradient of 0% - 20% ethyl acetate in hexanes) to give the title compound (1.3 g) as a white foam.

[0513] MS(ES + )m / z Found: (M+H) + , C 17 H 15 ClINO3, 444.2, theoretical value 444.0.

[0514] Step E: Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[5-(3-isopropyl-1,2,4-triazol-1-yl)-2-methoxy-phenyl]methanone

[0515] [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-(5-iodo-2-methoxy-phenyl)methanone (ie, the product of step D) (1.03 g, 2.32 mmol), 3-isopropyl-1H-1,2,4-triazole (0.31 g, 2.79 mmol), potassium carbonate (0.64 g, 4.64 mmol) and copper (I) iodide (88 mg, 0.46 mmol) were charged into a dry vial and then purged with nitrogen for 10 min. Anhydrous N, N-dimethylformamide (8 mL) was added, the mixture was bubbled with nitrogen for 5 min, and then trans-N, N′-dimethylcyclohexane-1,2-diamine (0.18 mL, 1.16 mmol) was added. The mixture was stirred at 105° C. overnight, then cooled to room temperature and filtered through a celite pad. The filtrate was washed with water (x3), filtered through a plug of silica gel and concentrated. The crude material was purified by reverse phase chromatography using a C18 column (gradient of water / acetonitrile) to give the title compound (630 mg) as a white solid.

[0516] MS(ES + )m / z Found: (M+H)+ , C 22 H 23 ClN4O3, 427.4, theoretical value 427.2.

[0517] Synthesis Example 2

[0518] Preparation of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methyl-5-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 74) and [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methyl-5-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 126)

[0519] Step A: Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-(5-iodo-2-methyl-phenyl)methanone

[0520] _______________________________________________________________

[0521] At 0°C, to a stirred solution of (2S)-8-chloro-2-methyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C in Synthesis Example 1) (1.0 g, 5.4 mmol), 5-iodo-2-methyl-benzoic acid (1.4 g, 5.4 mmol), and N,N-diisopropylethylamine (2.4 mL, 13.6 mmol) in ethyl acetate (15 mL) was added propylphosphonic anhydride (50 wt.%, in ethyl acetate, 5.2 mL, 8.7 mmol). The mixture was stirred at room temperature overnight and then heated at 70°C for 24 h. The mixture was cooled to room temperature, and additional N,N-diisopropylethylamine (2.4 mL, 13.6 mmol) and propylphosphonic anhydride (50 wt.%, in ethyl acetate, 5.2 mL, 8.7 mmol) were added, and the mixture was then stirred at 70°C for 22 h. The mixture was cooled to room temperature and water was added. The layers were separated, the aqueous phase was extracted with ethyl acetate, and the combined organic extracts were washed with 1N aqueous hydrochloric acid solution, brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-20% ethyl acetate in hexane) to obtain the title compound containing 5-iodo-2-methyl-benzoic acid. The material was dissolved in ethyl acetate, washed with 1N aqueous sodium hydroxide solution (×2), brine (×1), dried over anhydrous sodium sulfate and concentrated to obtain the title compound (1.6 g) as a white foam.

[0522] MS(ES + )m / z Found: (M+H) + , C 17 H 15 ClINO2, 428.1, theoretical value 428.0.

[0523] Step B: Preparation of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methyl-5-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl]methanone (isomer 1) (Compound 74) and [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methyl-5-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl]methanone (isomer 2) (Compound 126)

[0524] _______________________________________________________________

[0525] [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-(5-iodo-2-methyl-phenyl)methanone (ie, the product of step A) (0.18 g, 0.42 mmol), 3-methyl-1H-1,2,4-triazole (42 mg, 0.50 mmol), potassium carbonate (0.12 g, 0.88 mmol) and copper (I) iodide (8.0 mg, 0.04 mmol) were charged into a dry vial and then purged with nitrogen for 10 min. Anhydrous N, N-dimethylformamide (3 mL) and trans-N, N′-dimethylcyclohexane-1,2-diamine (0.02 mL, 0.13 mmol) were added, and the mixture was stirred at 110° C. for 19 h. The mixture was cooled to room temperature, diluted with ethyl acetate and saturated aqueous sodium bicarbonate solution and stirred for 10 min. The layers were separated, the aqueous layer was extracted with ethyl acetate (×1), and the combined organic extracts were washed with brine (×2), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-100% ethyl acetate in hexanes) to give the title compound as isomer 1 (90 mg) as a white solid and isomer 2 (24 mg) as a yellow oil.

[0526] Isomer 1: MS (ES + )m / z Found: (M+H) + , C 20 H 19 ClN4O2, 383.4, theoretical value 383.1. Isomer 2: MS (ES + )m / z Found: (M+H)+ , C 20 H 19 ClN4O2, 383.4, theoretical value 383.1.

[0527] Synthesis Example 3

[0528] Preparation of [3-(3-bromo-1H-1,2,4-triazol-1-yl)phenyl][(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]methanone (Compound 61)

[0529] Step A: Preparation of methyl (2S)-2-(2-methyl-6-nitro-phenoxy)propionate

[0530] _______________________________________________________________

[0531] (R)-(+)-methyl lactate (9.4mL, 98mmol) is added to a stirred mixture of 2-methyl-6-nitro-phenol (10g, 65mmol) and triphenylphosphine (22g, 85mmol) in anhydrous tetrahydrofuran (100mL). The mixture is cooled to 0 ° C, and then a solution of diisopropyl azodicarboxylate (17mL, 85mmol) in anhydrous tetrahydrofuran (20mL) is slowly added. The reaction mixture is stirred at room temperature overnight and then concentrated. A mixture of hexane and ether (1: 1, 350mL) is added and the mixture is stirred for 1h, resulting in the formation of a precipitate. The mixture is filtered through a diatomaceous earth pad, rinsed with hexane / ether (1: 1, 150mL) and the filtrate is concentrated. The crude material is purified by column chromatography on silica gel (gradient of 0%-30% ethyl acetate in hexane) to obtain the title compound (14.5g) as a yellow oil.

[0532] 1 H NMR(CDCl3)δ7.65–7.63(m,1H),7.41–7.39(m,1H),7.12–7.08(m,1H),4.56(q,1H),3.71(s,3H),2.38(s,3H),1.60(d,3H).

[0533] Step B: Preparation of (2S)-2,8-dimethyl-4H-1,4-benzoxazin-3-one

[0534] _______________________________________________________________

[0535] At 50 ° C, to a stirred solution of (2S)-2-(2-methyl-6-nitro-phenoxy)propionic acid methyl ester (i.e., the product of step A) (13,9 g, 58,2 mmol) in ethanol (210 mL), a solution of ammonium chloride (6.2 g, 116 mmol) in water (23 mL) was added. Then when the reaction mixture was heated from 50 ° C to 70 ° C, iron powder (9.7 g, 175 mmol) was added portionwise over 15 min. After stirring at 70 ° C for 23 h, the mixture was cooled to room temperature and filtered through a diatomaceous earth pad. The filtrate was concentrated, and ethyl acetate and water were then added. The layers were separated and the aqueous phase was extracted with ethyl acetate (× 1). The combined organic extracts were washed with saturated aqueous ammonium chloride solution (× 1), dried over anhydrous magnesium sulfate, filtered through a diatomaceous earth pad and concentrated to provide the title compound (9.2 g) as a white solid, which was used without further purification.

[0536] 1 H NMR(CDCl3)δ7.80(br s,1H),6.87–6.83(m,2H),6.64–6.60(m,1H),4.66(q,1H),2.25(s,3H),1.58(d,3H).

[0537] Step C: Preparation of (2S)-2,8-dimethyl-3,4-dihydro-2H-1,4-benzoxazine

[0538] _______________________________________________________________

[0539] At 0 ° C, over 30 min, to a stirred solution of (2S)-2,8-dimethyl-4H-1,4-benzoxazine-3-one (i.e., the product of step B) (10.3 g, 58 mmol) in anhydrous tetrahydrofuran (100 mL) was added borane tetrahydrofuran complex (1M, in tetrahydrofuran, 116 mL, 116 mmol). The reaction mixture was stirred at room temperature overnight, then cooled to 0 ° C and methanol (70 mL) was slowly added. After stirring at room temperature for 1 h, the mixture was concentrated and distributed between ethyl acetate and water. The layers were separated, and the organic phase was washed with water (×1), brine (×1), dried over anhydrous magnesium sulfate and concentrated to give the title compound (9.4 g) as a light brown oil, which was used without further purification.

[0540] 1H NMR(CDCl3)δ6.68–6.65(m,1H),6.57–6.55(m,1H),6.48–6.46(m,1H),4.28–4.22(m,1H),3.68(br s,1H),3.34(dd,1H),3.10(dd,1H),2.20(s,3H),1.40(d,3H).

[0541] Step D: Preparation of [(2S)-2,8-dimethyl-2,3-dihydro-1,4-benzoxazin-4-yl]-(3-iodophenyl)methanone

[0542] _______________________________________________________________

[0543] To a stirred solution of (2S)-2,8-dimethyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C) (8.5 g, 52 mmol), 3-iodobenzoic acid (12.9 g, 52 mmol) and triethylamine (17 mL, 120 mmol) in 1,2-dichloroethane (125 mL) was slowly added propylphosphonic anhydride (50 wt.%, in ethyl acetate, 50 mL, 84 mmol). The mixture was stirred at 60 ° C for 15 h, then cooled to room temperature and water was added. The layers were separated, the aqueous phase was extracted with dichloromethane (×1), and the combined organic extracts were washed with 1N aqueous hydrochloric acid solution (×1) and 1N aqueous sodium hydroxide solution (×1). The sodium hydroxide layer was extracted with dichloromethane (×1), and the combined organic extracts were then washed with brine (×1), dried over anhydrous magnesium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0% - 20% ethyl acetate in hexanes) to give the title compound as a white foam (17.6 g).

[0544] 1 H NMR(CDCl3)δ7.88–7.87(m,1H),7.77–7.74(m,1H),7.38–7.37(m,1H),7.07–7.04(m,1H),6.88–6.87(m ,1H),6.81–6.47(m,2H),4.50–4.44(m,1H),4.37–4.23(m,1H),3.33(dd,1H),2.22(s,3H),1.43(d,3H).

[0545] Step E: Preparation of [3-(3-bromo-1H-1,2,4-triazol-1-yl)phenyl][(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]methanone

[0546] _______________________________________________________________

[0547] [(2S)-2,8-dimethyl-2,3-dihydro-1,4-benzoxazin-4-yl]-(3-iodophenyl)methanone (ie, the product of step D) (1.14 g, 2.89 mmol), 3-bromo-1H-1,2,4-triazole (0.51 g, 3.47 mmol), potassium carbonate (0.84 g, 6.1 mmol) and copper (I) iodide (55 mg, 0.29 mmol) were charged into a dry vial and then purged with nitrogen for 10 min. Anhydrous N,N-dimethylformamide (11 mL) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.14 mL, 0.87 mmol) were added, and the mixture was stirred at 110° C. for 17 h. The mixture was cooled to room temperature and diluted with water and ethyl acetate. The layers were separated, the aqueous phase was extracted with ethyl acetate (×2), and the combined organic extracts were washed with water (×3), brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-60% ethyl acetate in hexanes) to give the title compound as a slightly green solid. The solid was dissolved in ethyl acetate, washed with saturated aqueous ammonium chloride solution (×3), dried over anhydrous sodium sulfate and concentrated to give the title compound as a light yellow solid (0.62 g).

[0548] 1 H NMR(CDCl3)δ8.33(s,1H),7.77–7.72(m,2H),7.50–7.47(m,2H),6.89–6.88(m,1H),6.69–6 .37(m,2H),4.55–4.48(m,1H),4.46–4.32(m,1H),3.36(dd,1H),2.23(s,3H),1.46(d,3H).

[0549] Synthesis Example 4

[0550] Preparation of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(1-methyl-1H-pyrazol-4-yl)phenyl]methanone (Compound 119)

[0551] _______________________________________________________________

[0552] To a stirred solution of (2S)-8-chloro-2-methyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C in Synthesis Example 1) (91 mg, 0.49 mmol), 3-(1-methylpyrazole-4-yl)benzoic acid (90 mg, 0.44 mmol) and triethylamine (0.21 mL, 1.5 mmol) in 1,2-dichloroethane (3 mL) was added propylphosphonic anhydride (50 wt.%, in ethyl acetate, 0.63 mL, 1.1 mmol). The mixture was stirred at 70 ° C for 24 h, then cooled to room temperature and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-50% ethyl acetate in hexane) to obtain the title compound (124 mg) as white foam.

[0553] 1 H NMR(CDCl3)δ7.72(s,1H),7.62–7.61(m,1H),7.58(s,1H),7.55–7.53(m,1H),7.36–7.32(m,1H),7.28–7.26(m,1H),7.11–7.0 9(m,1H),6.99–6.86(m,1H),6.62–6.59(m,1H),4.59–4.53(m,1H),4.32–4.29(m,1H),3.95(s,3H),3.44(dd,1H),1.48(d,3H).

[0554] Synthesis Example 5

[0555] Preparation of [3-(3-cyclopentyl-1H-1,2,4-triazol-1-yl)phenyl][(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]methanone (Compound 80)

[0556] _______________________________________________________________

[0557] A stirred solution of [3-(3-bromo-1H-1,2,4-triazol-1-yl)phenyl][(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]methanone (i.e., the product of Synthesis Example 3) (136 mg, 0.33 mmol) in anhydrous tetrahydrofuran (1 mL) was bubbled briefly (about 1 min) with nitrogen, and then [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (24 mg, 0.03 mmol) was added. Cyclopentylzinc bromide (0.5 M in tetrahydrofuran, 2.6 mL, 1.3 mmol) was added dropwise at room temperature, and the mixture was stirred at 60° C. for 1 h. The mixture was cooled to room temperature and saturated aqueous ammonium chloride solution was added. The mixture was extracted with ethyl acetate (×2), and the combined organic extracts were washed with brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0% - 100% ethyl acetate in hexanes) to give the title compound as a light orange foam (53 mg).

[0558] 1 H NMR(CDCl3)δ8.33(s,1H),7.80–7.73(m,2H),7.47–7.39(m,2H),6.89–6.87(m,1H),6.76–6.45(m,2H),4.55–4.47(m,1H),4.44–4.32(m ,1H),3.36(dd,1H),3.28(p,1H),2.23(s,3H),2.14–2.07(m,2H),1.95–1.88(m,2H),1.87–1.79(m,2H),1.74–1.67(m,2H),1.45(d,3H).

[0559] Synthesis Example 6

[0560] Preparation of [(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl][3-(3-ethynyl-1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 64)

[0561] Step A: Preparation of [(2S)-2,8-dimethyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[3-[3-(2-trimethylsilylethynyl)-1,2,4-triazol-1-yl]phenyl]methanone

[0562] _______________________________________________________________

[0563] A dry vial was charged with [3-(3-bromo-1H-1,2,4-triazol-1-yl)phenyl][(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]methanone (i.e., the product of Synthesis Example 3) (134 mg, 0.32 mmol), copper (I) iodide (12 mg, 0.06 mmol), anhydrous N,N-dimethylformamide (3 mL) and triethylamine (0.09 mL, 0.65 mmol), and the mixture was bubbled with nitrogen for 4 min. Ethyltrimethylsilane (0.23 mL, 1.6 mmol) was added, the mixture was bubbled with nitrogen for 2 min, and then tetrakis(triphenylphosphine)palladium(0) (70 mg, 0.06 mmol) was added, and the mixture was stirred at 50° C. for 13 h. The mixture was cooled to room temperature, then diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution (×2), brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-60% ethyl acetate in hexanes) to give the title compound (98 mg) as a brown foam.

[0564] 1 H NMR(CDCl3)δ8.41(s,1H),7.81–7.75(m,2H),7.49–7.45(m,2H),6.89–6.87(m,1H),6.76–6.41(m ,2H),4.55–4.47(m,1H),4.44–4.32(m,1H),3.36(dd,1H),2.23(s,3H),1.45(d,3H),0.29(s,9H).

[0565] Step B: Preparation of [(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl][3-(3-ethynyl-1H-1,2,4-triazol-1-yl)phenyl]methanone

[0566] _______________________________________________________________

[0567] To a solution of [(2S)-2,8-dimethyl-2,3-dihydro-1,4-benzoxazine-4-yl]-[3-[3-(2-trimethylsilylethynyl)-1,2,4-triazol-1-yl]phenyl]methanone (i.e., the product of step A) (81 mg, 0.19 mmol) in methanol (4 mL) was added potassium carbonate (30 mg, 0.22 mmol). The mixture was stirred at room temperature for 4.5 h, then filtered through a pad of celite, rinsed with ethyl acetate and the filtrate was concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-50% ethyl acetate in hexane) to give the title compound (42 mg) as a pale yellow foam.

[0568] 1 H NMR(CDCl3)δ8.42(s,1H),7.81–7.76(m,2H),7.50–7.47(m,2H),6.89–6.88(m,1H),6.76–6.39(m ,2H),4.56–4.48(m,1H),4.45–4.33(m,1H),3.36(dd,1H),3.17(s,1H),2.23(s,3H),1.46(d,3H).

[0569] Synthesis Example 7

[0570] Preparation of [(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl][3-[3-(methoxymethyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone (Compound 101)

[0571] _______________________________________________________________

[0572] A dry 40 mL vial was charged with [3-(3-bromo-1H-1,2,4-triazol-1-yl)phenyl][(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]methanone (i.e., the product of Synthesis Example 3) (104 mg, 0.25 mmol), potassium trifluoro(methoxymethyl)borohydride (78 mg, 0.52 mmol), [Ir(dF(CF3)ppy)2(bpy)]PF6 (5.3 mg, 0.005 mmol) and [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine]nickel(II) chloride (5.3 mg, 0.013 mmol), and then purged with nitrogen for 8 min. Anhydrous, degassed 1,4-dioxane (4.8 mL) was added, followed by 2,6-lutidine (0.10 mL, 0.88 mmol), and the mixture was then stirred and irradiated with two blue Kessil LED lamps (one 34 W and one 40 W, approximately 4 cm apart, with a cooling fan to keep the temperature from rising significantly) for 18 h. The mixture was partitioned between water and ethyl acetate, the layers were separated and the aqueous phase was extracted with ethyl acetate (×2). The combined organic extracts were washed with brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-100% ethyl acetate in hexane) to give the title compound (45 mg) as a pale yellow foam.

[0573] 1 H NMR(CDCl3)δ8.42(s,1H),7.82–7.76(m,2H),7.48–7.43(m,2H),6.89–6.87(m,1H),6.76–6.41(m,2H),4 .63(s,2H),4.55–4.48(m,1H),4.44–4.31(m,1H),3.51(s,3H),3.36(dd,1H),2.23(s,3H),1.45(d,3H).

[0574] Synthesis Example 8

[0575] Preparation of [(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl][3-[3-(3-oxetanyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone (Compound 109)

[0576] _______________________________________________________________

[0577] A dry 40 mL vial was charged with [3-(3-bromo-1H-1,2,4-triazol-1-yl)phenyl][(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazine-4-yl]methanone (i.e., the product of Synthesis Example 3) (101 mg, 0.24 mmol), [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 (3.5 mg, 0.003 mmol) and [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine]nickel(II) chloride (9.1 mg, 0.023 mmol), and then purged with nitrogen for 7 min. Anhydrous, degassed 1,4-dioxane (3 mL) was added, followed by 2,6-lutidine (0.14 mL, 1.2 mmol), tris(trimethylsilyl)silane (0.11 mL, 0.36 mmol) and 3-bromooxetane (0.04 mL, 0.48 mmol), and the mixture was bubbled with nitrogen for 6 min. The mixture was stirred and irradiated with two blue Kessil LED lamps (one 34 W and one 40 W, approximately 6 cm apart, with a cooling fan to keep the temperature from rising significantly) for 18 h. The mixture was diluted with saturated aqueous sodium bicarbonate solution (2 mL) and water (1 mL), then extracted with a 4:1 mixture of dichloromethane / isopropanol (×2) and dichloromethane (×1). The combined organic extracts were washed with brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0% - 80% ethyl acetate in hexanes) to give the title compound as a white foam (33 mg).

[0578] 1 H NMR(CDCl3)δ8.42(s,1H),7.82–7.75(m,2H),7.48–7.43(m,2H),6.89–6.88(m,1H),6.78–6 .44(m,2H),5.06–5.02(m,4H),4.56–4.34(m,3H),3.37(dd,1H),2.24(s,3H),1.46(d,3H).

[0579] Synthesis Example 9

[0580] Preparation of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methanone (Compound 127)

[0581] Step A: Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-(3-iodophenyl)methanone

[0582] _______________________________________________________________

[0583] At 0°C, to a stirred solution of (2S)-8-chloro-2-methyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C in Synthesis Example 1) (1.5 g, 8.2 mmol) in dichloromethane (45 mL) was added N,N-diisopropylethylamine (2.1 mL, 12 mmol), followed by 3-iodobenzoyl chloride (2.3 g, 8.6 mmol). The mixture was stirred at room temperature overnight, then diluted with dichloromethane, washed with 1N aqueous hydrochloric acid solution (×1), 1N aqueous sodium hydroxide solution (×1), brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-30% ethyl acetate in hexane) to give the title compound (3.27 g) as a white foam.

[0584] 1 H NMR(CDCl3)δ7.87(m,1H),7.80–7.78(m,1H),7.40–7.38(m,1H),7.12–7.08(m,2H), 6.96–6.61(m,2H),4.57–4.51(m,1H),4.30–4.22(m,1H),3.40(dd,1H),1.47(d,3H).

[0585] Step B: Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone

[0586] _______________________________________________________________

[0587] [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazine-4-yl]-(3-iodophenyl)methanone (i.e., the product of step A) (204 mg, 0.49 mmol), bis(pinacolato)diboron (163 mg, 0.64 mmol), potassium acetate (145 mg, 1.48 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (18 mg, 0.025 mmol) were charged to a dry vial and then purged with nitrogen. Anhydrous dimethyl sulfoxide (3 mL) was added and the mixture was stirred at 80° C. overnight. The mixture was cooled to room temperature and diluted with water and ethyl acetate. The layers were separated, the aqueous phase was extracted with ethyl acetate (×1), and the combined organic extracts were washed with water (×1), brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0% - 100% ethyl acetate in hexanes) to give the title compound as a light yellow foam (187 mg).

[0588] 1 H NMR(CDCl3)δ7.98–7.97(m,1H),7.89–7.87(m,1H),7.52–7.49(m,1H),7.37–7.34(m,1H),7.09–6.90(m,2H ),6.63–6.59(m,1H),4.55–4.49(m,1H),4.29–4.20(m,1H),3.40(dd,1H),1.45(d,3H),1.35–1.33(m,12H).

[0589] Step C: Preparation of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(2-methyl-2H-1,2,3-triazol-4-yl)phenyl]methanone

[0590] _______________________________________________________________

[0591] A microwave vial was charged with [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanone (ie, the product of step B) (174 mg, 0.42 mmol), 4-bromo-2-methyl-1,2,3-triazole (136 mg, 0.84 mmol), sodium carbonate (147 mg, 1.39 mmol), 1,2-dimethoxyethane (4 mL) and water (1.4 mL), and the mixture was then bubbled with nitrogen for 5 min. Tetrakis(triphenylphosphine)palladium(0) (48 mg, 0.042 mmol) was added, and the vial was then sealed and stirred in a microwave at 140° C. for 25 min. The mixture was cooled to room temperature, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate solution (×2), brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-100% ethyl acetate in hexanes) to give the title compound (107 mg) as a light yellow foam.

[0592] 1 H NMR(CDCl3)δ7.94–7.93(m,1H),7.87–7.85(m,1H),7.80(s,1H),7.44–7.39(m,2H),7.11–6.87(m,2H ),6.62–6.59(m,1H),4.59–4.53(m,1H),4.34–4.28(m,1H),4.24(s,3H),3.44(dd,1H),1.48(d,3H).

[0593] Synthesis Example 10

[0594] Preparation of 4-[3-[[(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]carbonyl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 122)

[0595] Step A: Preparation of 3-(5-oxo-1H-1,2,4-triazol-4-yl)benzoic acid

[0596] _______________________________________________________________

[0597] To a stirred solution of methyl 3-aminobenzoate (2 g, 13 mmol) in methanol (20 mL) was added trimethyl orthoformate (1.4 mL, 12.6 mmol), methyl hydrazinecarboxylate (1.13 g, 12.6 mmol) and p-toluenesulfonic acid monohydrate (50 mg, 0.26 mmol), and the mixture was stirred at 65 ° C for 48 h. Sodium methoxide (25 wt.%, in methanol, 8.58 g, 39.7 mmol) was added and the mixture was stirred at 50 ° C overnight, then cooled to room temperature and diluted with water. 1N sodium hydroxide aqueous solution was added, and the mixture was washed with ether (×3). The aqueous phase was acidified to pH about 2 with 1N hydrochloric acid aqueous solution and extracted with ethyl acetate (×2), and the combined organic extracts were then washed with water (×1), brine (×1), dried over anhydrous magnesium sulfate and concentrated to obtain the title compound (396 mg) as a pale pink solid, which was used without further purification.

[0598] 1 H NMR(CDCl3)δ8.49–8.26(m,1H),8.06(s,1H),7.94(m,1H),7.73–7.70(m,1H),7.54–7.52(m,1H),7.14–7.10(m,1H).

[0599] Step B: Preparation of 4-[3-[[(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]carbonyl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

[0600] _______________________________________________________________

[0601] To a stirred solution of (2S)-2,8-dimethyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C in Synthesis Example 3) (315 mg, 1.9 mmol), 3-(5-oxo-1H-1,2,4-triazol-4-yl)benzoic acid (i.e., the product of step A) (396 mg, 1.9 mmol) and triethylamine (0.81 mL, 5.8 mmol) in ethyl acetate (10 mL) was added propylphosphonic anhydride (50 wt.%, in ethyl acetate, 3.07 g, 4.8 mmol). The mixture was stirred under reflux overnight, then cooled to room temperature and diluted with ethyl acetate. The mixture was washed with 1N aqueous hydrochloric acid solution (×1), 1N aqueous sodium hydroxide solution (×1), water (×1), brine (×1), dried over anhydrous magnesium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0% - 40% ethyl acetate in hexanes) to give the title compound as a white solid (228 mg).

[0602] 1 H NMR(CDCl3)δ9.27(br s,1H),7.75–7.73(m,1H),7.63–7.60(m,2H),7.49–7.45(m,2H),6.90–6.88(m,1H),6.83–6 .41(m,2H),4.54–4.46(m,1H),4.42–4.30(m,1H),3.37(dd,1H),2.23(s,3H),1.44(d,3H).

[0603] Synthesis Example 11

[0604] Preparation of 4-[3-[[(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]carbonyl]phenyl]-2,4-dihydro-2-methyl-3H-1,2,4-triazol-3-one (Compound 117)

[0605] _______________________________________________________________

[0606] To a stirred solution of 4-[3-[[(2S)-2,3-dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl]carbonyl]phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (i.e., the product of Synthesis Example 10) (80 mg, 0.23 mmol) in N,N-dimethylformamide (4 mL) was added potassium carbonate (63 mg, 0.46 mmol) and iodomethane (0.04 mL, 0.69 mmol). The mixture was stirred at room temperature overnight, then water was added and the mixture was extracted with diethyl ether (×2). The combined organic extracts were washed with water (×1), brine (×1), dried over anhydrous magnesium sulfate and concentrated to give the title compound (52 mg) as a light tan solid.

[0607] 1 H NMR(CDCl3)δ7.75–7.73(m,1H),7.61–7.59(m,2H),7.46–7.42(m,2H),6.88–6.86(m,1H),6 .81–6.36(m,2H),4.55–4.19(m,2H),3.52(s,3H),3.35(dd,1H),2.21(s,3H),1.42(d,3H).

[0608] Synthesis Example 12

[0609] Preparation of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 18)

[0610] _______________________________________________________________

[0611] To a stirred solution of (2S)-8-chloro-2-methyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C in Synthesis Example 1) (1 g, 5.4 mmol), 3-(1,2,4-triazol-1-yl)benzoic acid (i.e., the product of step E in Synthesis Example 15) (1.03 g, 5.4 mmol) and triethylamine (1.9 mL, 13.6 mmol) in ethyl acetate (10 mL) was added propylphosphonic anhydride (50 wt.%, in ethyl acetate, 5.2 g, 8.2 mmol). The mixture was stirred at 70° C. overnight and then at 60° C. for 2 days. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate. The organic extract was washed with 1N aqueous hydrochloric acid solution (×1), 1N aqueous sodium hydroxide solution (×1), water (×1), brine (×1), dried over anhydrous magnesium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0% - 40% ethyl acetate in hexanes) to give the title compound (1.48 g) as a white solid.

[0612] 1 H NMR(CDCl3)δ8.55(s,1H),8.05(s,1H),7.86–7.85(m,1H),7.78–7.75(m,1H),7.47–7.44(m,1H),7.41–7.38(m,1H),7.0 7–7.05(m,1H),6.97–6.70(m,1H),6.57–6.54(m,1H),4.55–4.50(m,1H),4.32–4.20(m,1H),3.40(dd,1H),1.43(d,3H).

[0613] Synthesis Example 13

[0614] Preparation of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(1H-1,2,4-triazol-1-yl)phenyl]methanethione (Compound 139)

[0615] _______________________________________________________________

[0616] To a stirred solution of [(2S)-8-chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazine-4-yl] [3-(1H-1,2,4-triazol-1-yl) phenyl] ketone (i.e., the product of Synthesis Example 12) (200 mg, 0.56 mmol) in toluene (5 mL), Lawesson's reagent (228 mg, 0.56 mmol) was added. The mixture was stirred at 90 ° C overnight, then cooled to room temperature, diluted with water, extracted with ethyl acetate (× 2) and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%–50% ethyl acetate in hexane) to obtain the title compound (200 mg) as a yellow solid.

[0617] 1 H NMR(CDCl3)δ8.50(br s,1H),8.07(s,1H),7.98–7.71(m,1H),7.65–7.63(m,1H),7.38–7.09(m,3H),6.47– 6.44(m,2H),5.44–5.08(m,1H),4.76–4.70(m,1H),4.04–3.67(m,1H),1.58(d,3H).

[0618] Synthesis Example 14

[0619] Preparation of [8-chloro-2,3-dihydro-2-(methoxymethyl)-4H-1,4-benzoxazin-4-yl][2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]methanone (Compound 35)

[0620] Step A: Preparation of N-(3-chloro-2-fluorophenyl)-4-methylbenzenesulfonamide

[0621] _______________________________________________________________

[0622] To a stirred solution of 3-chloro-2-fluoroaniline (50 g, 345 mmol) in pyridine (300 mL) was added p-toluenesulfonyl chloride (72 g, 379 mmol) at 0 ° C, and the mixture was stirred at room temperature for 16 h. Ice-cold water (1000 mL) was added and the mixture was extracted with ethyl acetate (1000 ml × 2). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by trituration with n-pentane to obtain the title compound (55 g) as an off-white solid.

[0623] MS(ES + )m / z Found: (M–H) – , C 13H 11 ClFNO2S, 298, theoretical value 298.0.

[0624] Step B: Preparation of N-(3-chloro-2-fluoro-phenyl)-N-(2,3-dihydroxypropyl)-4-methyl-benzenesulfonamide

[0625] _______________________________________________________________

[0626] To a stirred mixture of N-(3-chloro-2-fluorophenyl)-4-methylbenzenesulfonamide (ie, the product of step A) (50 g, 167 mmol) and glycidol (13.6 g, 184 mmol) was added potassium carbonate (2.6 g, 17 mmol) and benzyltriethylammonium chloride (3.7 g, 17 mmol), and the mixture was stirred neat at 90 ° C for 16 h. Ice-cold water (1000 mL) was added and the mixture was extracted with ethyl acetate (1000 mL×2). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to give the title compound (52 g) as a colorless liquid. MS (ES + )m / z Found: (M+H) + , C 16 H 17 ClFNO4S, 374, theoretical value 374.1.

[0627] Step C: Preparation of N-[3-[tert-butyl(dimethyl)silyl]oxy-2-hydroxy-propyl]-N-(3-chloro-2-fluoro-phenyl)-4-methyl-benzenesulfonamide

[0628] _______________________________________________________________

[0629] At 0 ° C, imidazole (10.4 g, 153 mmol) and tert-butyldimethylsilyl chloride (23.0 g, 153 mmol) were added to a stirred solution of N-(3-chloro-2-fluoro-phenyl)-N-(2,3-dihydroxypropyl)-4-methyl-benzenesulfonamide (i.e., the product of step B) (52 g, 139 mmol) in dichloromethane (500 mL). The mixture was stirred at room temperature for 16 h, then ice-cold water (1000 mL) was added and the mixture was extracted with ethyl acetate (1000 mL×2). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to give the title compound (50 g) as a colorless liquid.

[0630] MS(ES + )m / z Found: (M+H) + , C 22 H 31 ClFNO4SSi, 488, theoretical value 488.1.

[0631] Step D: Preparation of [8-chloro-4-(p-tolylsulfonyl)-2,3-dihydro-1,4-benzoxazin-2-yl]methanol

[0632] _______________________________________________________________

[0633] To a stirred solution of N-[3-[tert-butyl(dimethyl)silyl]oxy-2-hydroxy-propyl]-N-(3-chloro-2-fluoro-phenyl)-4-methyl-benzenesulfonamide (i.e., the product of step C) (20 g, 41 mmol) in tetrahydrofuran (20 mL) was added sodium hydroxide (6.5 g, 164 mmol) and tetrabutylammonium bromide (1.32 g, 4.10 mmol), and the mixture was stirred at 70 ° C for 1 h. Ice-cold water (500 mL) was added and the mixture was extracted with ethyl acetate (500 mL×2). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to give the title compound (4.5 g) as an off-white solid. In addition, tert-butyl-[[8-chloro-4-(p-tolylsulfonyl)-2,3-dihydro-1,4-benzoxazin-2-yl]methoxy]-dimethyl-silane (5 g) was isolated.

[0634] MS(ES + )m / z Found: (M+H) + , C 16 H 16ClNO4S, 354, theoretical value 354.1.

[0635] Step E: Preparation of 8-chloro-2-(methoxymethyl)-4-(p-tolylsulfonyl)-2,3-dihydro-1,4-benzoxazine

[0636] _______________________________________________________________

[0637] At 0 ° C, sodium hydride (60% dispersion in mineral oil, 0.26 g, 6.5 mmol) was added to a stirred solution of [8-chloro-4-(p-tolylsulfonyl)-2,3-dihydro-1,4-benzoxazine-2-yl]methanol (i.e., the product of step D) (2 g, 5.7 mmol) in tetrahydrofuran (20 mL). The mixture was stirred at this temperature for 15 min, and then iodomethane (1.2 g, 8.5 mmol) was added. The mixture was stirred at room temperature for 3 h, and then ice-cold water (100 mL) was added. The mixture was extracted with ethyl acetate (100 mL×2), and the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to give the title compound (1 g) as an off-white solid. MS (ES + )m / z Found: (M+H) + , C 17 H 18 ClNO4S, 368, theoretical value 368.1.

[0638] Step F: Preparation of 8-chloro-2-(methoxymethyl)-3,4-dihydro-2H-1,4-benzoxazine

[0639] _______________________________________________________________

[0640] At 0 ° C, sulfuric acid (2.6 mL) was added to a stirred solution of 8-chloro-2-(methoxymethyl)-4-(p-tolylsulfonyl)-2,3-dihydro-1,4-benzoxazine (i.e., the product of step E) (1 g, 2.7 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 16 h and then quenched with solid sodium bicarbonate. Ethyl acetate (50 mL) was added and the mixture was filtered through a pad of celite and rinsed with ethyl acetate (50 mL). The filtrate was concentrated and the crude material was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to give the title compound (0.3 g) as a colorless liquid.

[0641] MS(ES + )m / z Found: (M+H) + , C 10 H 12 ClNO2, 214, theoretical value 214.1.

[0642] Step G: Preparation of 2-(1,2,4-triazol-1-yl)pyridine-4-carboxylic acid

[0643] _______________________________________________________________

[0644] To a mixture of ethyl 2-bromoisonicotinate (5g, 21.7mmol) and 1,2,4-triazole (1.79g, 25.9mmol) in N,N-dimethylformamide (50mL) was added cesium carbonate (14.1g, 43.5mmol) and cuprous iodide (I) (1.65g, 8.69mmol), and the mixture was then stirred at 120°C for 16h. The mixture was filtered through a diatomaceous earth pad and rinsed with N,N-dimethylformamide (50mL). The filtrate was diluted with water (100mL) and acidified with 1N aqueous hydrochloric acid. The resulting precipitate was collected by filtration, washed with ice-cold water and dried under vacuum to obtain the title compound (3g) as an off-white solid.

[0645] 1 H NMR(DMSO-d6)δ14.06(br s,1H),9.44(s,1H),8.74–8.72(m,1H),8.36(s,1H),8.22(s,1H),7.89–7.88(m,1H).

[0646] Step H: [8-Chloro-2,3-dihydro-2-(methoxymethyl)-4H-1,4-benzoxazin-4-yl][2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]methanone

[0647] _______________________________________________________________

[0648] Thionyl chloride (2.4 mL) was added to 2-(1,2,4-triazol-1-yl)pyridine-4-carboxylic acid (ie, the product of step G) (0.2 g, 1.05 mmol), and the mixture was stirred at 100 ° C for 2 h. The mixture was concentrated, then dichloromethane (10 mL) was added and the solution was cooled to 0 ° C. 8-chloro-2-(methoxymethyl)-3,4-dihydro-2H-1,4-benzoxazine (ie, the product of step F) (0.26 g, 1.22 mmol) and triethylamine (0.31 g, 3.06 mmol) were added, and the mixture was stirred at room temperature for 16 h. Ice-cold water (100 mL) was added and the mixture was extracted with dichloromethane (100 mL×2). The combined organic extracts were washed with brine (×1), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (50% ethyl acetate in hexanes) to give the title compound as an off-white solid (80 mg).

[0649] 1 H NMR(DMSO-d6,100℃)δ9.28(s,1H),8.61–8.60(m,1H),8.22–8.18(m,1H),7.93(s,1H),7.53–7.52(m,1H),7.30–7.28 (m,1H),7.20–7.18(m,1H),6.78–6.74(m,1H),4.69–4.67(m,1H),4.09–4.05(m,1H),3.74–3.58(m,3H),3.32(s,3H).

[0650] Synthesis Example 15

[0651] Preparation of (+)-[(2S)-2,3-dihydro-8-methyl-2-(trifluoromethyl)-4H-1,4-benzoxazin-4-yl][3-(1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 58) and (-)-[(2R)-2,3-dihydro-8-methyl-2-(trifluoromethyl)-4H-1,4-benzoxazin-4-yl][3-(1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 68)

[0652] Step A: Preparation of N-(3-chloro-2-fluoro-phenyl)-4-methyl-N-(3,3,3-trifluoro-2-hydroxy-propyl)benzenesulfonamide

[0653] _______________________________________________________________

[0654] To a stirred mixture of N-(3-chloro-2-fluorophenyl)-4-methylbenzenesulfonamide (i.e., the product of step A in Synthesis Example 14) (20 g, 67 mmol) and 2-(trifluoromethyl)oxirane (8.2 g, 74 mmol) was added potassium carbonate (0.92 g, 6.7 mmol) and benzyltriethylammonium chloride (1.51 g, 6.7 mmol), and the mixture was then stirred neat at 90 ° C for 24 h. Ice-cold water (500 mL) was added and the mixture was extracted with ethyl acetate (500 mL×2). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (20% ethyl acetate in hexane) to obtain the title compound (10 g) as an off-white solid.

[0655] MS(ES + )m / z Found: (M+H) + , C 16 H 14 ClF4NO3S, 412, theoretical value 412.0.

[0656] Step B: Preparation of 8-chloro-4-(p-tolylsulfonyl)-2-(trifluoromethyl)-2,3-dihydro-1,4-benzoxazine

[0657] _______________________________________________________________

[0658] To a stirred solution of N-(3-chloro-2-fluoro-phenyl)-4-methyl-N-(3,3,3-trifluoro-2-hydroxy-propyl)benzenesulfonamide (i.e., the product of step A) (3 g, 7.3 mmol) in tetrahydrofuran (2 mL) was added sodium hydroxide (1.16 g, 29.7 mmol) and tetrabutylammonium bromide (0.22 g, 0.7 mmol), and the mixture was stirred at 70 ° C for 1 h. Ice-cold water (100 mL) was added and the mixture was extracted with ethyl acetate (100 mL×2). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to give the title compound (2.2 g) as an off-white solid.

[0659] MS(ES + )m / z Found: (M+H) + , C 16 H 13 ClF3NO3S, 392, theoretical value 392.0.

[0660] Step C: Preparation of 8-methyl-4-(p-tolylsulfonyl)-2-(trifluoromethyl)-2,3-dihydro-1,4-benzoxazine

[0661] _______________________________________________________________

[0662] 8-chloro-4-(p-tolylsulfonyl)-2-(trifluoromethyl)-2,3-dihydro-1,4-benzoxazine (i.e., the product of step B) (1 g, 2.55 mmol), toluene (5 mL), methylboric acid (1.5 g, 25 mmol) and potassium phosphate (1.0 g, 4.7 mmol) were charged into a sealed tube, and the mixture was then bubbled with argon for 10 min. Palladium acetate (II) (57 mg, 0.25 mmol) and SPhos (0.2 g, 0.48 mmol) were added, the tube was then sealed and the mixture was stirred at 120 ° C for 16 h. The reaction was carried out four times, and then the four reaction mixtures were combined, treated and purified together. Ice-cold water was added and the mixture was extracted with ethyl acetate (× 2). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (5% ethyl acetate in hexane) to obtain the title compound (1.1 g) as an off-white solid. MS (ES + )m / z Found: (M+H) + , C 17 H 16 F3NO3S, 372, theoretical value 372.1.

[0663] Step D: Preparation of 8-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine

[0664] _______________________________________________________________

[0665] At 0 ° C, magnesium powder (1 g, 40 mmol) was added to a solution of 8-methyl-4-(p-tolylsulfonyl)-2-(trifluoromethyl)-2,3-dihydro-1,4-benzoxazine (i.e., the product of step C) (1.5 g, 4.0 mmol) in methanol (10 mL), and the mixture was sonicated at room temperature for 2 h. Ethyl acetate (100 mL) was added, the mixture was filtered through a celite pad and the filtrate was concentrated. The crude material was purified by column chromatography on silica gel (10% ethyl acetate in hexane) to give the title compound (0.7 g) as a yellow oil. MS (ES + )m / z Found: (M+H)+ , C 10 H 10 F3NO, 218, theoretical value 218.1.

[0666] Step E: Preparation of 3-(1,2,4-triazol-1-yl)benzoic acid

[0667] _______________________________________________________________

[0668] To a mixture of ethyl 3-iodobenzoate (20g, 87mmol) and 1,2,4-triazole (7.1g, 103mmol) in N, N-dimethylformamide (100mL) was added cesium carbonate (56.5g, 172mmol) and cuprous iodide (I) (6.65g, 34.8mmol), and the mixture was then stirred at 120°C for 16h. The mixture was filtered through a diatomaceous earth pad and rinsed with N, N-dimethylformamide (50mL). The filtrate was diluted with water (100mL) and acidified with 1N aqueous hydrochloric acid solution. The resulting precipitate was collected by filtration, washed with ice-cold water and dried under vacuum to obtain the title compound (10g) as an off-white solid.

[0669] MS(ES + )m / z Found: (M+H) + , C9H7N3O2, 190, theoretical value 190.1.

[0670] Step F: Preparation of (+)-[(2S)-2,3-dihydro-8-methyl-2-(trifluoromethyl)-4H-1,4-benzoxazin-4-yl][3-(1H-1,2,4-triazol-1-yl)phenyl]methanone (Isomer 1) and (-)-[(2R)-2,3-dihydro-8-methyl-2-(trifluoromethyl)-4H-1,4-benzoxazin-4-yl][3-(1H-1,2,4-triazol-1-yl)phenyl]methanone (Isomer 2)

[0671] _______________________________________________________________

[0672] At 0°C, to a mixture of 8-methyl-2-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine (ie, the product of step D) (0.75 g, 3.45 mmol) and 3-(1,2,4-triazol-1-yl)benzoic acid (ie, the product of step E) (0.78 g, 4.14 mmol) in pyridine (20 mL) was added phosphorus oxychloride (1.5 g, 10.4 mmol). The mixture was stirred at 0°C for 2 h, and then ice-cold water (200 mL) was added. The mixture was extracted with ethyl acetate (200 mL×2), and the combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (5% ethyl acetate in hexanes) to give [8-methyl-2-(trifluoromethyl)-2,3-dihydro-1,4-benzoxazin-4-yl]-[3-(1,2,4-triazol-1-yl)phenyl]methanone (0.52 g) as a light yellow solid.

[0673] 1 H NMR(CDCl3)δ8.45(s,1H),8.10(s,1H),7.81–7.79(m,2H),7.48–7.40(m,2H),6.94–6.92(m,1H),6.60–6.56(m,1H),6.44(br s,1H),4.88–4.85(m,1H),4.36–4.32(m,1H),4.20–4.16(m,1H),2.29(s,3H).

[0674] The enantiomers were separated by chiral supercritical fluid chromatography to give the title compound.

[0675] Isomer 1: [α] 25 D = +17.2° (c = 0.1%, in CHCl3)

[0676] Isomer 2: [α] 25 D = -13.8° (c = 0.1%, in CHCl3)

[0677] Synthesis Example 16

[0678] Preparation of (8-chloro-2-cyclopropyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[3-(1H-1,2,4-triazol-1-yl)phenyl]methanone (Compound 22)

[0679] Step A: Preparation of 8-chloro-2-cyclopropyl-4H-1,4-benzoxazin-3-one

[0680] _______________________________________________________________

[0681] 2-amino-6-chloro-phenol (0.5 g, 3.5 mmol), 2-bromo-2-cyclopropyl-ethyl acetate (0.6 g, 2.9 mmol), 1,8-diazabicyclo [5.4.0] undec-7-ene (0.49 g, 3.2 mmol) and N-methyl-2-pyrrolidone (8 mL) were loaded into a microwave vial. The vial was sealed and stirred in a microwave at 180 ° C for 4 min. The mixture was cooled to room temperature, diluted with ethyl acetate and filtered through a diatomaceous earth pad. The filtrate was washed with brine (× 2) and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%–50% ethyl acetate in hexane) to obtain the title compound (0.51 g) as an orange solid.

[0682] 1 H NMR(CDCl3)δ8.45(br s,1H),7.06–7.05(m,1H),6.91–6.87(m,1H),6.73–6.71(m,1H),4.20(d,1H),1.33–1.26(m,1H),0.75–0.58(m,4H).

[0683] Step B: Preparation of 8-chloro-2-cyclopropyl-3,4-dihydro-2H-1,4-benzoxazine

[0684] _______________________________________________________________

[0685] At 0 ° C, 8-chloro-2-cyclopropyl-4H-1,4-benzoxazine-3-one (ie, the product of step A) (0.42 g, 1.9 mmol) was added dropwise to a stirred solution of anhydrous tetrahydrofuran (10 mL) of borane tetrahydrofuran complex (1 M, in tetrahydrofuran, 3.2 mL, 3.2 mmol). The reaction mixture was stirred at room temperature for 3 h, then stirred at 50 ° C overnight. The mixture was cooled to room temperature and methanol (5 mL) was slowly added. After stirring for 20 min, the mixture was concentrated, then dissolved in ethyl acetate and washed with saturated sodium bicarbonate aqueous solution (× 1), water (× 1), brine (× 1), dried over anhydrous magnesium sulfate and concentrated to give the title compound (0.37 g) as a light brown oil, which was used without further purification.

[0686] 1H NMR(CDCl3)δ6.73–6.71(m,1H),6.66–6.63(m,1H),6.49–6.47(m,1H),3.83(brs,1H),3.52–3.46(m, 2H),3.32–3.29(m,1H),1.14–1.08(m,1H),0.72–0.66(m,1H),0.64–0.57(m,2H),0.43–0.37(m,1H).

[0687] Step C: Preparation of (8-chloro-2-cyclopropyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[3-(1H-1,2,4-triazol-1-yl)phenyl]methanone

[0688] _______________________________________________________________

[0689] To a stirred solution of 8-chloro-2-cyclopropyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step B) (0.11 g, 0.52 mmol), 3-(1,2,4-triazole-1-yl)benzoic acid (i.e., the product of step E in Synthesis Example 15) (0.12 g, 0.63 mmol) and triethylamine (0.22 mL, 1.6 mmol) in dichloromethane (8 mL) was added propylphosphonic anhydride (50 wt.%, in ethyl acetate, 0.57 g, 0.90 mmol). The mixture was stirred at 40 ° C overnight, then cooled to room temperature and concentrated. The crude material was purified by column chromatography on silica gel (gradient of 0%-70% ethyl acetate in hexane). The separated material was further purified by column chromatography on silica gel (gradient of 0%-20% ethyl acetate in dichloromethane) to obtain the title compound (39 mg) as a colorless oil.

[0690] 1 H NMR(CDCl3)δ8.53(s,1H),8.10(s,1H),7.87–7.86(m,1H),7.80–7.78(m,1H),7.51–7.48(m,1H),7.44–7.42(m,1H),7.11–7.10(m,1H),6.82(br s,1H),6.60–6.57(m,1H),4.40–4.38(m,1H),3.87–3.83(m,1H),3.60(dd,1H) ,1.13–1.06(m,1H),0.74–0.68(m,1H),0.66–0.58(m,2H),0.47–0.41(m,1H).

[0691] Synthesis Example 17

[0692] Preparation of [(2R)-8-chloro-2-(ethoxymethyl)-2,3-dihydro-1,4-benzoxazin-4-yl]-[5-(3-isopropyl-1,2,4-triazol-1-yl)-2-methyl-phenyl]methanone (Compound 340)

[0693] Step A: Preparation of [(2R)-8-chloro-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methanol

[0694] _______________________________________________________________

[0695] To a stirred solution of 2-amino-6-chloro-phenol (10 g, 70 mmol) in water (100 mL) was added (S)-(+)-epichlorohydrin (7.7 g, 83 mmol) and sodium hydroxide (3.9 g, 98 mmol). The reaction mixture was stirred at room temperature for 20 min, then diluted with water, extracted with ethyl acetate (×2), and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (25% ethyl acetate in hexanes) to give the title compound (7 g) as a colorless liquid.

[0696] 1 H NMR(CDCl3)δ6.74(dd,1H),6.70–6.66(m,1H),6.50(dd,1H),4.32–4.28(m,1H),3.91–3.82(m,2H),3.42–3.39(m,1H),3.35–3.31(m,1H).

[0697] MS(ES + )m / z Found: (M+H) + , C9H 10 ClNO2, 200, theoretical value 200.0.

[0698] Step B: Preparation of (2R)-8-chloro-2-(ethoxymethyl)-3,4-dihydro-2H-1,4-benzoxazine

[0699] _______________________________________________________________

[0700] At 0 ° C, sodium hydride (60% dispersion in mineral oil, 0.8 g, 20 mmol) and iodoethane (2.3 g, 15 mmol) were added to a stirred solution of [(2R)-8-chloro-3,4-dihydro-2H-1,4-benzoxazin-2-yl]methanol (i.e., the product of step A) (2 g, 10 mmol) in anhydrous tetrahydrofuran (20 mL). The reaction mixture was stirred at room temperature for 1 h, then diluted with water, extracted with ethyl acetate (×2), and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (15% ethyl acetate in hexane) to give the title compound (1.5 g) as a colorless liquid.

[0701] 1 H NMR(CDCl3)δ6.72(dd,1H),6.68–6.65(m,1H),6.49(dd,1H),4.39–4.35(m,1H) ),3.75(dd,1H),3.66–3.55(m,3H),3.48(dd,1H),3.28(dd,1H),1.22(t,3H). MS(ES + )m / z Found: (M+H) + , C 11 H 14 ClNO2, 228, theoretical value 228.1.

[0702] Step C: Preparation of 5-(3-isopropyl-1,2,4-triazol-1-yl)-2-methyl-benzoic acid methyl ester

[0703] _______________________________________________________________

[0704] A microwave vial was charged with 5-bromo-2-methyl-benzoic acid methyl ester (2.5 g, 11 mmol), anhydrous N, N-dimethylformamide (15 mL) and 3-isopropyl-1H-1,2,4-triazole (1.83 g, 16.5 mmol), and the mixture was then bubbled with nitrogen for 10 min. Potassium carbonate (4.55 g, 33 mmol), cuprous iodide (I) (418 mg, 2.2 mmol) and trans-N, N'-dimethylcyclohexane-1,2-diamine (0.86 ml, 5.5 mmol) were added, and the mixture was then stirred in a microwave at 110 ° C for 3 h. The mixture was cooled to room temperature, diluted with water and extracted with ethyl acetate (× 2). The combined organic extracts were filtered through a diatomaceous earth pad, rinsed with ethyl acetate (25 mL), and the filtrate was then washed with brine (× 1) and concentrated. The crude material was purified by column chromatography on silica gel (20% ethyl acetate in hexanes) to give the title compound as an off-white solid (2.4 g). MS (ES) + )m / z Found: (M+H) + , C 14 H 17 N3O2, 260, theoretical value 260.1.

[0705] Step D: Preparation of 5-(3-isopropyl-1,2,4-triazol-1-yl)-2-methyl-benzoic acid

[0706] _______________________________________________________________

[0707] To the stirring solution of 5-(3-isopropyl-1,2,4-triazole-1-yl)-2-methyl-benzoic acid methyl ester (i.e. the product of step C) (2.4g, 9.3mmol) in tetrahydrofuran (7mL) and water (3mL) add lithium hydroxide monohydrate (583mg, 13.9mmol). The reaction mixture is stirred at room temperature for 16h. The mixture is concentrated, then diluted with water (20mL) and acidified with citric acid. The obtained precipitate is collected by filtration and dried under vacuum to obtain the title compound (1.6g) as off-white solid.

[0708] MS(ES + )m / z Found: (M+H) + , C 13 H 15 N3O2, 246, theoretical value 246.1.

[0709] Step E: Preparation of [(2R)-8-chloro-2-(ethoxymethyl)-2,3-dihydro-1,4-benzoxazin-4-yl]-[5-(3-isopropyl-1,2,4-triazol-1-yl)-2-methyl-phenyl]methanone

[0710] _______________________________________________________________

[0711] At 0 ° C, to a stirred solution of 5-(3-isopropyl-1,2,4-triazol-1-yl)-2-methyl-benzoic acid (i.e., the product of step D) (600 mg, 2.4 mmol) in pyridine (6 mL) was added (2R)-8-chloro-2-(ethoxymethyl)-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step B) (555 mg, 2.4 mmol) and phosphorus oxychloride (0.68 mL, 7.3 mmol). The reaction mixture was stirred at room temperature for 16 h and then concentrated. The crude material was purified by column chromatography on silica gel (25% ethyl acetate in hexane) to give the title compound (232 mg) as brown foam.

[0712] 1 H NMR(DMSO-d6,90℃)δ8.96(s,1H),7.79–7.76(m,2H),7.43–7.41(m,2H),7.18–7.16(m,1H),6.79–6.76(m,1H),4.59–4.57( m,1H),4.09–4.06(m,1H),3.67–3.58(m,2H),3.54–3.47(m,3H),3.07–3.01(m,1H),2.28(s,3H),1.29(d,6H),1.03(t,3H).

[0713] MS(ES + )m / z Found: (M+H) + , C 24 H 27 ClN4O3, 455.3, theoretical value 455.2.

[0714] Synthesis Example 18

[0715] Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[5-(3-isopropyl-1,2,4-triazol-1-yl)-2,3-dimethoxy-phenyl]methanone (Compound 194)

[0716] Step A: Preparation of (5-bromo-2,3-dimethoxy-phenyl)-[(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]methanone

[0717] _______________________________________________________________

[0718] At 0 ° C, thionyl chloride (1.3 mL, 18 mmol) was added to a stirred solution of 5-bromo-2,3-dimethoxy-benzoic acid (1 g, 3.8 mmol) and a few drops of N,N-dimethylformamide in chloroform (10 mL). The reaction mixture was stirred at 60 ° C for 3 h, then cooled to room temperature and concentrated. The crude acyl chloride was then dissolved in dichloromethane (10 mL) and added to a solution of (2S)-8-chloro-2-methyl-3,4-dihydro-2H-1,4-benzoxazine (i.e., the product of step C in Synthesis Example 1) (697 mg, 3.8 mmol) and pyridine (1 mL, 12 mmol) in dichloromethane (10 mL) at 0 ° C. The mixture was stirred at room temperature for 16 h, then diluted with water, extracted with dichloromethane (× 2), and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (30% ethyl acetate in hexanes) to give the title compound as a colorless liquid (1.3 g).

[0719] MS(ES + )m / z Found: (M+H) + , C 18 H 17 BrClNO4, 426.1, theoretical value 426.0.

[0720] Step B: Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[5-(3-isopropyl-1,2,4-triazol-1-yl)-2,3-dimethoxy-phenyl]methanone

[0721] _______________________________________________________________

[0722] A solution of (5-bromo-2,3-dimethoxy-phenyl)-[(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazine-4-yl]methanone (i.e., the product of step A) (400 mg, 0.94 mmol) in N,N-dimethylformamide (4 mL) was bubbled with nitrogen, followed by the addition of potassium carbonate (389 mg, 2.8 mmol), copper (I) iodide (89 mg, 0.47 mmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (0.074 ml, 0.47 mmol). The reaction mixture was stirred at 120° C. for 16 h in a sealed tube. The mixture was cooled to room temperature, diluted with water, extracted with ethyl acetate (×2), and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated. The crude material was purified by column chromatography on silica gel (35% ethyl acetate in hexanes) to give the title compound as an off-white semisolid (270 mg).

[0723] 1 H NMR(DMSO-d6,90℃)δ8.99(s,1H),7.56–7.38(m,3H),7.16–7.14(m,1H),6.74(m,1H),4.52(m,1H),4. 05(m,1H),3.91(s,3H),3.67(m,3H),3.41–3.37(m,1H),3.07–3.03(m,1H),1.36(d,3H),1.30(d,6H).

[0724] MS(ES + )m / z Found: (M+H) + , C 23 H 25 ClN4O4, 457.27, theoretical value 457.16.

[0725] Synthesis Example 19

[0726] Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[2,3-dihydroxy-5-(3-isopropyl-1,2,4-triazol-1-yl)phenyl]methanone (Compound 272)

[0727] _______________________________________________________________

[0728] To a stirred solution of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazine-4-yl]-[5-(3-isopropyl-1,2,4-triazol-1-yl)-2,3-dimethoxy-phenyl]methanone (i.e., the product of Synthesis Example 18) (3 g, 6.6 mmol) in dichloromethane (60 mL) was added boron tribromide (1 M in dichloromethane, 39.5 ml, 39.5 mmol) dropwise at -30 °C. The mixture was stirred at room temperature for 1 h, then cooled to 0 °C and methanol (100 mL) was added. The mixture was concentrated, then diluted with water (25 mL), extracted with ethyl acetate (×2), and the combined organic extracts were dried over anhydrous sodium sulfate and concentrated. The crude material was purified by trituration with n-pentane to give the title compound (2.55 g) as a brown solid.

[0729] 1 H NMR(DMSO-d6,90℃)δ8.83(m,1H),7.51–7.49(m,1H),7.30–7.29(m,1H),7.18(m,1H),7.13–7.11(m,1H),6.76 –6.71(m,1H),4.55–4.51(m,1H),4.07–4.03(m,1H),3.40–3.35(m,1H),3.05–3.02(m,1H),1.35–1.25(m,9H).

[0730] MS(ES + )m / z Found: (M+H) + , C 21 H 21 ClN4O4, 429.09, theoretical value 429.13.

[0731] Synthesis Example 20

[0732] Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[6-(3-isopropyl-1,2,4-triazol-1-yl)-1,3-benzodioxol-4-yl]methanone (Compound 258)

[0733] _______________________________________________________________

[0734] To a stirred solution of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazine-4-yl]-[2,3-dihydroxy-5-(3-isopropyl-1,2,4-triazol-1-yl)phenyl]methanone (i.e., the product of Synthesis Example 19) (300 mg, 0.7 mmol) in anhydrous N,N-dimethylformamide (5 mL) was added cesium carbonate (1.8 g, 5.5 mmol) and bromochloromethane (0.45 g, 3.5 mmol). The mixture was stirred at 90 ° C for 6 h, then cooled to room temperature and ice-cold water (10 mL) was added. The solid material was collected by filtration and dried to provide a crude product. Purification was performed on silica gel (30% ethyl acetate in hexane) by column chromatography to give the title compound (100 mg) as a white solid.

[0735] 1 H NMR(CDCl3)δ8.36(s,1H),7.34(d,1H),7.23(d,1H),7.10–7.08(m,1H),7.02–6.40(m,2H),5.92–5. 40(m,2H),4.63–4.13(m,2H),3.55–3.30(m,1H),3.16–3.08(m,1H),1.48–1.43(m,3H),1.36(d,6H).

[0736] MS(ES + )m / z Found: (M+H) + , C 22 H 21 ClN4O4, 441.21, theoretical value 441.13.

[0737] Synthesis Example 21

[0738] Preparation of [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazin-4-yl]-[7-(3-isopropyl-1,2,4-triazol-1-yl)-2,3-dihydro-1,4-benzodioxin-5-yl]methanone (Compound 217)

[0739] _______________________________________________________________

[0740] A microwave vial was charged with [(2S)-8-chloro-2-methyl-2,3-dihydro-1,4-benzoxazine-4-yl]-[2,3-dihydroxy-5-(3-isopropyl-1,2,4-triazol-1-yl)phenyl]methanone (i.e., the product of Synthesis Example 19) (400 mg, 0.93 mmol), acetone (8 mL), cesium carbonate (2.4 g, 7.4 mmol) and dibromoethane (0.8 mL, 9.3 mmol). The mixture was stirred in a microwave at 90 ° C for 30 min. The mixture was cooled to room temperature and the solid was removed by filtration, rinsed with acetone (10 mL). The filtrate was concentrated, and the resulting crude material was purified by preparative HPLC to give the title compound (170 mg) as a light brown solid.

[0741] 1 H NMR(DMSO-d6,90℃)δ8.93(s,1H),7.41–7.14(m,4H),6.74–6.70(m,1H),4.53(m,1H) ,4.22–3.95(m,5H),3.47–3.40(m,1H),3.07–2.98(m,1H),1.37(d,3H),1.29(d,6H).

[0742] MS(ES + )m / z Found: (M+H) + , C 23 H 23 ClN4O4, 455.27, theoretical value 455.15

[0743] The following compounds in Tables 1 to 236 can be prepared by the procedures described herein together with methods known in the art. The following abbreviations are used in the following tables: t means tert-, s means secondary, n means normal, i means iso, c means cyclo, Me means methyl, Et means ethyl, Pr means propyl, Bu means butyl, i-Pro means isopropyl, c-Pro means cyclopropyl, t-Bu means tert-butyl, Ph means phenyl, OMe means methoxy, OEt means ethoxy, SMe means thiomethoxy, -CN means cyano, -NO2 means nitro, TMS means trimethylsilyl, SOMe means methylsulfinyl, C2F5 means CF2CF3 and SO2Me means methylsulfonyl.

[0744] Table 1

[0745]

[0746] R 1b It is H, X 1 It is CH, X 2 is CH, (R 2 )n is 6-OMe, Y is O, (R 3b ) p Yes H, R 3a It's Me, R 4a is Cl and (R 4b ) q It's H.

[0747]

[0748]

[0749] Some of the J groups in these tables are defined below.

[0750]

[0751]

[0752]

[0753] Table 2 is constructed in the same way, except that the row headers “R 1b It is H, X 1 It is CH, X 2 is CH, (R 2 ) n is 6-OMe, Y is O, (R 3b ) p Yes H, R 3a It's Me, R 4a is Cl and (R 4b ) q is H. " is replaced by the row headings listed in Table 2 below (i.e. "R 1b It is H, X 1 It is CH, X 2 is CH, (R 2 ) n is H, Y is O, (R 3b ) p Yes H, R 3a It's Me, R 4a is Cl and (R 4b ) q is H. ”). Thus, the first entry in Table 2 is a compound of Formula 1, wherein R 1b It is H, X 1 It is CH, X 2 is CH, (R 2 ) n is H, Y is O, (R 3b ) p Yes H, R 3a It's Me, R 4a is Cl, (R4b ) q is H and R 1a is H. Tables 3 to 230 are constructed similarly.

[0754]

[0755]

[0756]

[0757]

[0758]

[0759]

[0760]

[0761]

[0762]

[0763]

[0764]

[0765]

[0766] Table 231

[0767]

[0768]

[0769]

[0770] Table 232 is constructed in the same manner as Table 1, except that the row headers “R 1b It is H, X 1 It is CH, X 2 is CH, (R 2 ) n is 6-OMe, Y is O, (R 3b ) p Yes H, R 3a It's Me, R 4a is Cl and (R 4b ) q is H. " is replaced by the row headings listed in Table 232 below (i.e. "R 1b It is H, X 1 It is CH, X 2Together with C6, it forms J-34, where Y is O, (R 3b ) p Yes H, R 3a It's Me, R 4a is Cl and (R 4b ) q is H. ”). Thus, the first entry in Table 232 is a compound of Formula 1, wherein R 1b It is H, X 1 It is CH, X 2 Together with C6, it forms J-34, where Y is O, (R 3b ) p Yes H, R 3a It's Me, R 4a is Cl, (R 4b ) q is H and R 1a is H. Tables 233 to 236 are constructed similarly.

[0771]

[0772] Formulation / Efficacy

[0773] The compounds of the present invention will generally be used as herbicidal active ingredients in compositions (i.e. formulations) wherein at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents is used as a carrier. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, the mode of application and environmental factors such as soil type, moisture and temperature.

[0774] Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions, oil-in-water emulsions, flowable concentrates and / or suspoemulsions) that can optionally be thickened into gels, etc. The general types of aqueous liquid compositions are soluble concentrates, suspending agents, capsule suspensions, concentrated emulsions, microemulsions, oil-in-water emulsions, flowable concentrates and suspoemulsions. The general types of non-aqueous liquid compositions are emulsifiable concentrates, microemulsifiable concentrates, dispersible concentrates and oil dispersions.

[0775] The general types of solid compositions are dusts, powders, granules, pellets, pellets, pastilles, tablets, filled films (including seed coatings), etc., which can be water-dispersible ("wettable") or water-soluble. Films and coatings formed by film-forming solutions or flowable suspensions are particularly useful for seed treatment. The active ingredient can be (micro) encapsulated and further formed into a suspension or solid formulation; alternatively, the entire formulation of the active ingredient can be encapsulated (or "coated"). Encapsulation can control or delay the release of the active ingredient. Emulsifiable granules combine the advantages of both emulsifiable concentrate formulations and dry granular formulations. High-strength compositions are mainly used as intermediates for further formulations.

[0776] Sprayable formulations are typically dispersed in suitable media before spraying. Such liquid and solid formulations are formulated in spray media, are generally water, but are occasionally another suitable medium that is easy to dilute as aromatic hydrocarbons or paraffin hydrocarbons or vegetable oils. The scope of spray volume can be from about one liter to several thousand liters per hectare, but more typically in the scope of about ten to several hundred liters per hectare. Sprayable formulations can be mixed with water or another suitable medium bucket, for carrying out leaf treatment by air or ground application, or for being applied to the growth medium of plant. Liquid and dry formulations can be directly metered in the drip irrigation system, or metered in the furrow during planting.

[0777] The formulation will typically contain effective amounts of active ingredient, diluent and surfactant totaling up to 100 weight percent within the following approximate ranges.

[0778]

[0779] Solid diluents include, for example, clays (such as bentonite, montmorillonite, attapulgite and kaolin), gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silicon dioxide, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Edition, Dorland Books, Caldwell, New Jersey.

[0780] Liquid diluents include, for example, water, N,N-dimethylalkaneamides (e.g., N,N-dimethylformamide), limonene, dimethyl sulfoxide, N-alkylpyrrolidones (e.g., N-methylpyrrolidone), alkyl phosphates (e.g., triethyl phosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, butylene carbonate, paraffins (e.g., white mineral oils, normal paraffins, isoparaffins), alkylbenzenes, alkylnaphthalenes, glycerols, triacetin, sorbitol, aromatic hydrocarbons, dearomatized aliphatic compounds, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone ketone and 4-hydroxy-4-methyl-2-pentanone, acetates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, other esters such as alkylated lactic acid esters, dibasic esters, alkyl and aryl benzoates and gamma-butyrolactone, and alcohols which may be linear, branched, saturated or unsaturated, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-hexanol, 2-ethylhexanol, n-octanol, decanol, isodecanol, isostearyl alcohol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol, cresol and benzyl alcohol. Liquid diluents also include saturated and unsaturated fatty acids (typically C6-C 22 ), such as plant seed and fruit oils (e.g., olive oil, castor oil, linseed oil, sesame oil, corn oil (maize oil), peanut oil, sunflower seed oil, grape seed oil, safflower oil, cottonseed oil, soybean oil, rapeseed oil, coconut oil and palm kernel oil), animal fats (e.g., tallow, lard, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated (e.g., methylated, ethylated, butylated) fatty acids, which can be obtained by hydrolysis of glycerides from plant and animal sources and purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd ed., Interscience, New York, 1950.

[0781] The solid and liquid compositions of the present invention typically contain one or more surfactants. When added to a liquid, a surfactant (also known as a "surfactant (surface-active agent)") typically changes, most often reduces, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilic groups in the surfactant molecule, the surfactant can be used as a wetting agent, dispersant, emulsifier or defoaming agent.

[0782] Surfactants can be classified as nonionic, anionic or cationic. Nonionic surfactants that can be used in the compositions of the present invention include, but are not limited to, alcohol alkoxylates, such as those based on natural and synthetic alcohols (which may be branched or linear) and prepared from alcohols and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides, such as ethoxylated soybean oil, castor oil and rapeseed oil; alkylphenol alkoxylates, such as octylphenol ethoxylate, nonylphenol ethoxylate, dinonylphenol ethoxylate and dodecylphenol ethoxylate (prepared from phenol and ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and trans-block polymers in which the terminal blocks are prepared from propylene oxide; Ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenols (including those prepared from ethylene oxide, propylene oxide, butylene oxide or mixtures thereof); fatty acid esters, glycerides, lanolin-based derivatives, polyethoxylated esters (such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitan fatty acid esters and polyethoxylated glycerol fatty acid esters); other sorbitan derivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycol (PEG); polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.

[0783] Useful anionic surfactants include, but are not limited to, alkylaryl sulfonic acids and salts thereof; carboxylated alcohol or alkylphenol ethoxylates; diphenylsulfonate derivatives; lignin and lignin derivatives, such as lignin sulfonates; maleic acid or succinic acid or their anhydrides; olefin sulfonates; phosphates, such as phosphates of alcohol alkoxylates, phosphates of alkylphenol alkoxylates, and phosphates of styrylphenol ethoxylates; protein-based surfactants; sarcosine derivatives; styrylphenol ether sulfates; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of ethoxylated alcohols; sulfonates of amines and amides, such as N,N-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecylbenzene and tridecylbenzene; sulfonates of polycondensed naphthalene; sulfonates of naphthalene and alkylnaphthalene; sulfonates of petroleum fractions; sulfosuccinamates; and sulfosuccinates and their derivatives, such as dialkylsulfosuccinates.

[0784] Useful cationic surfactants include, but are not limited to, amides and ethoxylated amides; amines such as N-alkylpropylenediamine, tripropylenetriamine and dipropylenetetramine, and ethoxylated amines, ethoxylated diamines, and propoxylated amines (prepared from amines and ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof); amine salts such as ammonium acetate and diamine salts; quaternary ammonium salts such as quaternary ammonium salts, ethoxylated quaternary salts, and diquaternary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

[0785] Also useful in the compositions of the present invention are mixtures of nonionic and anionic surfactants, or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a number of published references, including McCutcheon's Emulsifiers and Detergents, annual American and International Editions, published by The Manufacturing Confectioner Publishing Co., McCutcheon Division; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and AS Davidson and B. Milwidsky, Synthetic Detergents, Seventh Edition, John Wiley and Sons, New York, 1987.

[0786] The compositions of the present invention may also contain formulation aids and additives known to those skilled in the art as auxiliary formulations (some of which may also be considered to function as solid diluents, liquid diluents, or surfactants). Such formulation aids and additives may control: pH (buffers), foaming during processing (defoamers, such as polyorganosiloxanes), sedimentation of active ingredients (suspending agents), viscosity (thixotropic thickeners), microbial growth in containers (antimicrobial agents), product freezing (antifreeze agents), color (dye / pigment dispersions), elution (film formers or stickers), evaporation (evaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acetate, polyvinyl acetate copolymers, polyvinyl pyrrolidone-vinyl acetate copolymers, polyvinyl alcohol, polyvinyl alcohol copolymers, and waxes. Examples of formulation aids and additives include those listed in McCutcheon's Volume 2: Functional Materials, annual International and North American editions, published by the McCutcheon Division of Manufacturing Confectioner Publishing Company; and PCT Publication WO 03 / 024222.

[0787] The compound of formula 1 and any other active ingredient are typically incorporated into the composition of the present invention by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions including emulsifiable concentrates can be prepared by simply mixing these ingredients. If the solvent of the liquid composition intended to be used as an emulsifiable concentrate is immiscible with water, an emulsifier is typically added to emulsify the solvent containing the active ingredient when diluted with water. The active ingredient slurry with a particle size of up to 2,000 μm can be wet-milled using a media mill to obtain particles with an average particle size of less than 3 μm. The aqueous slurry can be made into a finished suspension (see, for example, US3,060,084) or further processed by spray drying to form water-dispersible granules. Dry preparations generally require a dry milling process to produce an average particle size in the range of 2 to 10 μm. Dusts and powders can be prepared by blending and usually by grinding (e.g., with a hammer mill or fluid energy mill). Granules and spherical agents can be prepared by spraying the active substance on a preformed granule carrier or by agglomeration techniques. See, Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp. 147-48; Perry's Chemical Engineer's Handbook, 4th edition, McGraw-Hill, New York, 1963, pp. 8-57 et seq., and WO 91 / 13546. Pellets may be prepared as described in US 4,172,714. Water-dispersible and water-soluble granules may be prepared as taught in US 4,144,050, US 3,920,442 and DE 3,246,493. Tablets may be prepared as taught in US 5,180,587, US 5,232,701 and US 5,208,030. Membranes may be prepared as taught in GB 2,095,558 and US 3,299,566.

[0788] For further information in the field of formulations, see TS Woods, "The Formulator's Toolbox-Product Forms for Modern Agriculture," in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and TR Roberts, eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, Cambridge, 1999, pp. 120-133. See also US 3,235,361, column 6, lines 16 to column 7, line 19, and Examples 10-41; US ​​3,309,192, column 5, lines 43 to column 7, line 62, and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167, and 169-182; US 2,891,855, column 3, lines 66 to column 5, line 17, and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pages 81-96; Hance et al., Weed Control Handbook, 8th ed., Blackwell Scientific Publications [Blackwell Scientific Publishers], Oxford, 1989; and Developments in formulation technology [Development of formulation technology] [PJB Publications [PJB Publishing Company], Richmond, UK, 2000.

[0789] In the following examples, all percentages are by weight, and all formulations are prepared in a conventional manner. Compound numbers refer to compounds in Index Tables AF. Without further elaboration, it is believed that one skilled in the art can utilize the present invention to its maximum extent using the previous description. Therefore, the following examples should be construed as merely illustrative and not limiting the present disclosure in any way. Unless otherwise stated, percentages are by weight.

[0790] Example A

[0791] High Strength Concentrate

[0792] Compound 1 98.5%

[0793] Silica Aerogel 0.5%

[0794] Synthetic amorphous fine silica 1.0%

[0795] Example B

[0796] Wettable powder

[0797]

[0798] Example C

[0799] Granules

[0800] Compound 1 10.0%

[0801] Attapulgite granules (low volatile matter, 0.71 / 0.30mm; USS90.0%

[0802] No. 25-50 sieve)

[0803] Example D

[0804] Extruded pellets

[0805]

[0806] Example E

[0807] Emulsifiable concentrates

[0808] Compound 1 10.0%

[0809] Polyoxyethylene sorbitan hexaoleate 20.0%

[0810] C6-C 10 Fatty acid methyl ester 70.0%

[0811] Example F

[0812] microemulsion

[0813]

[0814]

[0815] Example G

[0816] Suspension

[0817]

[0818] Example H

[0819] Emulsion in water

[0820]

[0821] Example I

[0822] oil dispersion

[0823]

[0824] The present disclosure also includes Examples A to I above, except that "Compound 1" is replaced by any one of "Compound 2" to "Compound 144" and "Compound 145" to "Compound 414"

[0825] The test results show that the compounds of the present invention are highly active pre-emergence and / or post-emergence herbicides and / or plant growth regulators. The compounds of the present invention generally show the highest activity for post-emergence weed control (i.e., application after weeds emerge from the soil) and pre-emergence weed control (i.e., application before weeds emerge from the soil). Many of them have utility for broad-spectrum pre-emergence and / or post-emergence weed control in areas where complete control of all vegetation is desired, such as around fuel tanks, industrial storage areas, parking lots, drive-in theaters, airports, riverbanks, irrigation and other waterways, billboards, and highway and railroad structures. Many of the compounds of the present invention can be used to selectively control grasses and broadleaf weeds in crop / weed mixtures by means of selective metabolism in crop contrast weeds, or by having selective activity at physiological inhibition sites in crops and weeds, or by selective application on or in environments where crops and weeds grow together. Those skilled in the art will recognize that within a compound or group of compounds, preferred combinations of these selectivity factors can be readily determined by performing conventional biological and / or biochemical assays. The compounds of the present invention can show tolerance to important crops, including but not limited to alfalfa, barley, cotton, wheat, oilseed vegetables, beets, corn (maize), sorghum, soybeans, rice, oats, peanuts, vegetables, tomatoes, potatoes, perennial crops, including coffee, cocoa, oilseed palm, rubber, sugar cane, citrus, grapes, fruit trees, nut trees, bananas, plantains, pineapples, hops, tea and trees such as eucalyptus and conifers (e.g., loblolly pine), and turf species (e.g., Kentucky bluegrass, St. Augustine grass, Kentucky fescue and Bermuda grass). The compounds of the present invention can be used in crops that have been genetically transformed or bred to incorporate herbicide resistance, express proteins that are toxic to invertebrate pests (such as Bacillus thuringiensis toxins) and / or express other useful traits. Those skilled in the art will appreciate that not all compounds are equally effective against all weeds.Alternatively, the subject compounds may be used to alter plant growth.

[0826] Since the compounds of the present invention have pre-emergence and post-emergence herbicidal activity, to control undesirable vegetation by killing or injuring vegetation or slowing its growth, the compounds are usually effectively applied by a variety of methods, which involve contacting the leaves or other parts of the undesirable vegetation with a herbicidally effective amount of the compounds of the present invention, or a composition comprising at least one of the compounds and a surfactant, a solid diluent or a liquid diluent, or contacting the environment of the undesirable vegetation, such as soil or water, in which the undesirable vegetation grows, or the environment surrounds the seeds or other propagules of the undesirable vegetation. The undesirable vegetation includes at least one selected from the group consisting of grass weeds and broadleaf weeds. Undesirable vegetation is selected from the group consisting of: annual bluegrass, Bengal dayflower, blackgrass, black nightshade, broadleaf signal grass, Canada thistle, brome grass, common cocklebur (Xanthium pensylvanicum), common ragweed, corn poppy, field violet, giant foxtail, goosegrass, green foxtail, geranium, bidens, herbicide-resistant blackgrass, small white wine grass, Italian ryegrass, datura, Johnson grass (Sorghum halepense), big crabgrass, small-seeded phragmites, morning glory, Pennsylvania Polygonum, seeded morning glory, prickly sida, wheatgrass, redroot wild amaranth, shattercane, shepherd's purse, silky windgrass, sunflower (as a weed in potatoes), wild buckwheat (Brassica kaber), wild oats (Avena fatua), wild poinsettia (wild pointsettia), yellow foxtail grass, and butter sedge (Cyperusesculentus).

[0827] The herbicidally effective amount of the compounds of the present invention is determined by many factors. These factors include: the selected formulation, the method of application, the amount and type of vegetation present, the growth conditions, etc. Typically, the herbicidally effective amount of the compounds of the present invention is about 0.001 kg / ha to 20 kg / ha, with a preferred range of about 0.004 kg / ha to 1 kg / ha. Those skilled in the art can easily determine the herbicidally effective amount required for the desired weed control level.

[0828] In a common embodiment, the compounds of the invention are applied to a site comprising desirable vegetation (e.g., crops) and undesirable vegetation (i.e., weeds), usually in a formulated composition, which may be seeds, seedlings, and / or larger plants in contact with a growing medium (e.g., soil). At this site, the composition comprising the compounds of the invention may be applied directly to the plant or a portion thereof, particularly the undesirable vegetation, and / or to the growing medium in contact with the plant.

[0829] Although most typically the compounds of the invention are used to control undesirable vegetation, contacting the desired vegetation with the compounds of the invention in the treated locus can result in superadditive or potentiating effects with the genetic traits of the desired vegetation, including traits introduced by genetic modification. For example, resistance to phytophagous pests or plant diseases, tolerance to biotic / abiotic stresses, or storage stability may be greater than expected in the genetic traits of the desired vegetation.

[0830] The compound of the present invention can also be mixed with one or more other biologically active compounds or agents to form a multi-component pesticide, thereby giving even wider agricultural protection, these biologically active compounds or agents include herbicides, herbicide safeners, fungicides, insecticides, nematicides, bactericides, acaricides, growth regulators such as insect molting inhibitors and rooting stimulants, chemical sterilants, chemical semiochemicals, insect repellents, attractants, pheromones, feeding stimulants, plant nutrients, other biologically active compounds or insect pathogenic bacteria, viruses or fungi. The mixture of the compound of the present invention and other herbicides can expand the range of activity against additional weed species and inhibit the proliferation of any resistant biological type. Therefore, the present invention also relates to a composition comprising a compound of Formula 1 (in a herbicidally effective amount) and at least one additional biologically active compound or agent (in a biologically effective amount), and the composition may further include at least one of a surfactant, a solid diluent or a liquid diluent. Other biologically active compounds or agents can be formulated into a composition comprising at least one of a surfactant, a solid or a liquid diluent. For the mixtures of the present invention, one or more other biologically active compounds or agents can be formulated together with the compound of Formula 1 to form a premix, or one or more other biologically active compounds or agents can be formulated separately from the compound of Formula 1 and the formulations combined together (e.g., in a spray tank) prior to application, or alternatively, applied sequentially.

[0831] Mixtures of one or more of the following herbicides with the compounds of the present invention can be particularly useful for weed control: acetochlor, acifluorfen and its sodium salt, fenthion, acrolein (2-propenal), alachlor, fenthion, ametryn, amitriptyline, amidosulfuron, cyproconazole and its esters (e.g., methyl, ethyl) and salts (e.g., sodium, potassium), 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-2-pyridinecarboxylic acid 2-propyn-1-yl ester (CAS No. 2251111-17-6), 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)-2-pyridinecarboxylic acid cyanomethyl ester (CAS No. 2251111-18-7), aminopyralid, cyproconazole, ammonia ammonium sulfonate, 2,5-anhydro-3,4-dideoxy-4-[[[(5S)-3-(3,5-difluorophenyl)-5-vinyl-4,5-dihydro-5-isoxazolyl]carbonyl]amino]-threo-pentosonic acid methyl ester (CAS No. 27499989-21-6), thiabendazole, flubendanine, sulfamethoxam, atrazine, tetrazosulfuron, dichloroisothiazone, flubutyric acid amide, flubutyric acid amide, chloranil, chloranil ethyl ester, bencarbazone, fluazifop, furazolidone, quinclorac, benzylsulfuron, dimethoate, bentazone, bicyclam, pyraclostrobin, pyraclostrobin, pyraclostrobin, pyraclostrobin, bifenthrin, bispyribac-butyl and its sodium salt, bromobutyric acid amide, bromophenol oxime, bromoxynil, bromophenol oxime Benzonitrile octanoate, butachlor, fluazifop-butyl, chlorpyrifos, butalin, butachlor, butachlor, bispyribac, benzophenone, carbamate, 1-(2-carboxyethyl)-4-(2-pyrimidinyl)pyridazinium (CAS No. 2285384-11-2) and its salts, triadimefon, catechin, methoxy-herbicide, chlorfenapyr, chlorbromid, chlormethyldan, herbicide, chlorsulfuron, 3-[2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl]-4,5-dihydro-5-methyl-5-isoxazolecarboxylic acid ethyl ester (CAS No. 1949837-17-5), chlorotoluron, chlorpropamide, chlorsulfuron, dimethyl chlorthalate, cypermethrin, indole indolecarb, cyproconazole, ethoxysulfuron, chloracylphosphine, cyproconazole, clethodim, clodinafop-butyl, isocyanate, barnyardgrass, clopyralid, clopyralid ethanolamine, clorac-sulfuron, benzylpyruvate, cyanazine, cyclopentyl, cyclopyrimidine, cyprosulfuron, cyfluthrin, 2,4-D and its butoxy, butyl, isooctyl and isopropyl esters and their dimethylammonium salts, diethanolamine salts and triethanolamine salts, cyprafluone, cyproconazole, dalafenamide, dalafenamide sodium, dazomethane, 2,4-DB and its dimethylammonium salts, potassium and sodium salts, betaine, dichlorvos, dicamba and its diethylene glycol ammonium salts, dimethylammonium salts, potassium and sodium salts, dichlorvos nitrile, dichlorprop, diclofenac, diclofenac, dimethyl sulfate,Fluazifop, fluazifop, oxazolidinone, piperidine, dimethosulfamide, dimethochlor, isopentan, dimethenamid, dimethenamid-P, thiamethoxam, dimethoate and its sodium salt, dimethomorph, telofen, dioxopyritrione, dimethomorph, diquat, fluthiopyr, diuron, DNOC, fentothiocarb, EPTC, fluazifop, pentocarb, ethidium bromide, ethidium bromide, ethidium bromide, chlorpyrifos, ethoxysulfuron, ethosulfuron, fenpyrazone, fenoxaprop-butyl, fenoxaprop-butyl, fenpyrazone, fenquinolone, tetrazoline, fenamuron, fenamuron-TCA, methyl pyrosulfate, methyl pyrosulfate, methyl pyrosulfate, fenpyrazone, fenpyrazone, fenpyrazone, fenpyrazone, fenpyrazone-TCA, methyl pyrosulfate, methyl pyrosulfate, fenpyrazone, fenpyrazone Flupyralid, fluazifop-butyl, fluazifop-butyl, flufenoximacil, flupyridazine, flusulfuron, fluazifop-butyl, flufenoximacil, flupyridazine, flupyridazine, flusulfuron, fluazifop-butyl, flufenoximacil, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine and its sodium salt, flupyridin, flufenoxim, flupyridazine, flupyridazine, flupyridazine, flupyridazine, flupyridazine and its sodium salt, flupyridin, flupyridin, flupyridazine ... for glufosinate), halochlorid, halochlorid methyl, clopidogrel, flupyralid, halochlorid, halopyralid, hexazinone, hydantoin, imazapic, methazapic, imazapic, imazapic, imazapic, imazapic, pyrazosulfuron, indole, triazine indole, iodosulfuron, methyl iodosulfuron, ioboxynil, ioboxynil octanoate, ioboxynil sodium, triazole, isoproturon, isoxazol, isoxazolamide, isoxathiocarb, isoxathiocarb, lactofen, lenacil, liuron, bud-inhibiting, MCPA and its salts (e.g., MCPA-dimethylammonium, MCPA-potassium and MCPA-sodium, esters (e.g., MCPA-2-ethylhexyl ester, MCPA-butoxyethyl ester) and thioesters (e.g., MCPA -ethylthioester), MCPB and its salts (e.g., MCPB-sodium) and esters (e.g., MCPB-ethyl ester), 2-methyl-4-chloropropionic acid, 2-methyl-4-chloropropionic acid, benzathine, fomesulfuron, mesosulfuron, mesotrione, sodium metamethyleneimine, metamethyleneimine, metamethyleneimine, pyraclostrobin, methylbenthiocarb, arsenic acid and its calcium salts, monoammonium, monosodium and disodium salts, methylthiocarb, methoxybenthiocarb, bromothiocarb, isopropylamine, isopropylamine, sulfamethoxam, sulfamethoxam, methoxythiocarb, methicillin, metsulfuron-methyl, chloranil, naphthamide, naphthamide, naphthamide-M, naphthamide, chloranil, nicosulfuron, dafosulfuron, pyraclostrobin, pyraclostrobin, amoxicillin, oxadiazine, oxadiazine, oxadiazine, oxadiazine, chloranil, naphthamide, naphthamide, naphthamide-M, naphthamide, chloranil, chloranil, naphthamide, naphthamide-M, naphthamide, chloranil, nicosulfuron, dafosulfuron, pyraclostrobin, chloranil ...Oxazimidone, oxyfluorfen, paraquat dichloride, chlorpyrifos, nonanoic acid, pendimethalin, penoxsulam, meclofenamide, cyclopentadione, fluazifop, pethoxamid, pethoxamid, pethoxyamid, bendiazole, picloram, picloram potassium, fluazifop, pinoxaden, pyraclofos, pretilachlor, primisulfuron, aminopropydroxypropydroxypropydroxypropydroxypropydroxypropydroxydroxy, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole, cyproconazole , dacaote, pyriflubenzoxim, pyriflubenzoxim, pyriflubenzoxim, pyrimisulfan, pyrimisulfan, pyrimisulfan sodium, rockweed sulfone, methoxysulfone, quinclorac, clomeclorac, algaquinone, quizalofop-p-ethyl, quizalofop-p-ethyl, quizalofop-p-ethyl, rimisoxafen, sulfonesulfuron, pyrimisoxafen, sethoxydim, cypermethrin, simazine, cypermethrin, sulfotrione, sulfosulfuron, sulfosulfuron, 2,3,6-TBA, TCA, TCA-sodium, oxadiazine, terbuthiazine, terbuthiazine, cypermethrin, tetraflurazon, methoxythiocarb oxadiazine, thiamethoxam, thiamethoxam, thifensulfuron-methyl, chloranil, fluazifop-butyl, chloranil, tolpyralate, benpyrazone, oxadiazine, wild oxadiazine, fluazifop-butyl, etherbensulfuron-methyl, triazifop-butyl, bensulfuron-methyl, triclopyr, triclopyr, triethylammonium, chloranil, trifloxysulfuron, trifludimoxazin, fluralin, flufenacil, tripyrasulfone, trifloxysulfuron, 3-(2-chloro-3,6-difluorophenyl)-4-hydroxy-1-methyl-1,5-naphthyridin-2(1H)-one, 5-chloro-3-[(2-hydroxy-6-oxy-1-cyclohexene-1 -yl)carbonyl]-1-(4-methoxyphenyl)-2(1H)-quinoxalinone, 2-chloro-N-(1-methyl-1H-tetrazol-5-yl)-6-(trifluoromethyl)-3-pyridinecarboxamide, 7-(3,5-dichloro-4-pyridyl)-5-(2,2-difluoroethyl)-8-hydroxypyrido[2,3-b]pyrazin-6(5H)-one), 4-(2,6-diethyl-4-methylphenyl)-5-hydroxy-2,6-dimethyl-3(2H)-pyridazinone), 5-[[(2,6-difluorophenyl)methoxy]methyl]-4,5-dihydro-5-methyl-3-(3-methyl-2-thienyl)isoxazole (the aforementioned is methioxolin),4-(4-Fluorophenyl)-6-[(2-hydroxy-6-oxy-1-cyclohexen-1-yl)carbonyl]-2-methyl-1,2,4-triazine-3,5(2H,4H)-dione, methyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoro-2-picolinate, 2-methyl-3-(methylsulfonyl)-N-(1-methyl-1H-tetrazol-5-yl)-4-(trifluoromethyl)benzamide, and 2-methyl-N-(4-methyl-1,2,5-oxadiazol-3-yl)-3-(methylsulfinyl)-4-(trifluoromethyl)benzamide. Other herbicides include bioherbicides such as Alternaria destruens Simmons, Colletotrichum gloeosporiodes (Penz.) Penz. & Sacc., Drechsieramonoceras (MTB-951), Myrothecium verrucaria (Albertini & Schweinitz) Ditmar: Fries, Phytophthora palmivora (Butl.) Butl., and Puccinia thlaspeos Schub.,

[0832] Preferred for better control of undesirable vegetation (e.g., lower use rates such as from an enhanced effect, a broader spectrum of weed control, or enhanced crop safety) or for preventing the development of resistant weeds are mixtures of a compound of the invention with a herbicide selected from the group consisting of atrazine, tetrazosulfuron-methyl, S-flubutyric acid, benzisothiazolinone, mefenacet-butyl, chlorimuron-methyl, chlorsulfuron-methyl, clomazone, clopyralid, clocambidom-potassium, clocambidom-sulfuron, 2-[(2,4-dichlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, 2-[(2,5 -dichlorophenyl)methyl]-4,4-dimethyl-3-isoxazolidinone, ethametsulfuron, fluazifop-butyl, 4-(4-fluorophenyl)-6-[(2-hydroxy-6-oxo-1-cyclohexen-1-yl)carbonyl]-2-methyl-1,2,4-triazine-3,5-(2H,4H)-dione, fluazifop-butyl, fluthiazol-butyl, fomesulfuron-butyl, imazethapyr, cypermethrin, mesotrione, metribuzin, metsulfuron-methyl, pethozone, piclopram, roxasulfone, quinclorac, sulfamethoxam, metolachlor, s-isopropylamine, sulfamethoxam, thifensulfuron-methyl, fluazifop-butyl and bensulfuron-methyl.

[0833] The compounds of the present invention can also be used in combination with plant growth regulators such as avermectin, N-(phenylmethyl)-1H-purin-6-amine, propionyl brassinolide, gibberellic acid, gibberellins A4 and A7, hypersensitive protein, mepiquat, prohexadione-calcium, jasmone, sodium nitrophenolate and trinexapac-ethyl-methyl, and plant growth modifying organisms such as Bacillus cereus strain BP01.

[0834] General references to agricultural protectants (i.e., herbicides, herbicide safeners, insecticides, fungicides, nematicides, acaricides, and bioagents) include The Pesticide Manual, 13th edition, ed. CDS Tomlin, British Crop Protection Council, Farnham, Surrey, UK, 2003 and The BioPesticide Manual, 2nd edition, ed. LG Copping, British Crop Protection Council, Farnham, Surrey, UK, 2001.

[0835] For embodiments in which one or more of these different mixing components are used, these mixing components are generally used in an amount similar to the conventional amount when the mixture components are used alone. More specifically, in the mixture, the active ingredient is generally applied in an amount between half and the total amount of the active ingredient indicated on the product label. These amounts are listed in references such as The Pesticide Manual [pesticide manual] and The BioPesticide Manual [biological pesticide manual]. The weight ratio of these different mixing components (total amount) to the compound of formula 1 is typically between about 1:3000 and about 3000:1. It is worth noting that the weight ratio between about 1:300 and about 300:1 (e.g., a ratio between about 1:30 and about 30:1). Those skilled in the art can easily determine the biologically effective amount of the active ingredient required for the desired biological activity spectrum by simple experiments. It will be apparent that the inclusion of these additional components can expand the controlled weed spectrum beyond the control spectrum of the compound of formula 1 alone.

[0836] In some cases, the combination of the compounds of the present invention and other biologically active (particularly herbicidal) compounds or agents (i.e., active ingredients) can result in an effect greater than the cumulative (i.e., enhanced) effect on weeds and / or an effect less than the cumulative (i.e., safening) effect on crops or other desired plants. It is desirable to reduce the amount of active ingredients released in the environment while ensuring effective pest control. It is also desirable to use a larger amount of active ingredients to provide more effective weed control without the ability to cause excessive crop damage. When the herbicidal mixture of active ingredients produces an enhanced effect on weeds at an application rate that obtains agronomically satisfactory weed control level, such combinations can be advantageously used to reduce crop production costs and reduce environmental loads. When the safening of herbicidal active ingredients occurs on crops, such combinations can be advantageously used to increase crop protection by reducing weed competition.

[0837] It is noteworthy that the combination of the compounds of the present invention and at least one other herbicidal active ingredient. It is particularly noteworthy that the combination of other herbicidal active ingredients and the compounds of the present invention has different action sites. In some cases, the combination with at least one other herbicidal active ingredient with a similar control range but a different action site will be particularly advantageous for resistance management. Therefore, the composition of the present invention may further comprise (in a herbicidally effective amount) at least one additional herbicidal active ingredient with a similar control range but a different action site.

[0838] The compounds of the present invention can also be used in combination with herbicide safeners such as dimethoate, chlorpyrifos, chlorpyrifos-butyl, benzylpyridin, chlorpyrifos-butyl, cyproconazole, cyproconazole, dichlorpropamide, cyclohexane, chlorpyrifos, chlorpyrifos, chlorpyrifos, chlorpyrifos, fluazifop, chlorpyrifos, isoxadiazole, chlorpyrifos-butyl, chlorpyrifos ... 4660), 2-(dichloromethyl)-2-methyl-1,3-dioxolane (MG191), 1,6-dihydro-1-(2-methoxyphenyl)-6-oxo-2-phenyl-5-pyrimidinecarboxylic acid ethyl ester, 2-hydroxy-N,N-dimethyl-6-(trifluoromethyl)pyridine-3-carboxamide, and 3-oxo-1-cyclohexene-1-yl 1-(3,4-dimethylphenyl)-1,6-dihydro-6-oxo-2-phenyl-5-pyrimidinecarboxylate, 2,2-dichloro-1-(2,2,5-trimethyl-3-oxazolidinyl)-ethanone and 2-methoxy-N-[[4-[[(methylamino)carbonyl]amino]phenyl]sulfonyl]-benzamide. The herbicide safener in an effective amount for detoxification can be applied simultaneously with the compound of the present invention or as a seed treatment. Therefore, one aspect of the present invention relates to a herbicidal mixture comprising a compound of the present invention and a detoxifying effective amount of a herbicide safener. Seed treatment is particularly useful for selective weed control because it physically limits the detoxifying effect to crop plants. Therefore, a particularly useful embodiment of the present invention is a method for selectively controlling undesirable vegetation growth in crops, the method comprising contacting the location of the crop with a herbicidally effective amount of a compound of the present invention, wherein the crop is treated with a detoxifying effective amount of a safener from the seed grown therefrom. The detoxifying effective amount of a safener can be easily determined by a person skilled in the art by simple experiments.

[0839] The compounds of the present invention may also be mixed with: (1) polynucleotides, including but not limited to DNA, RNA and / or chemically modified nucleotides, which affect the amount of a specific target by down-regulating, interfering, inhibiting or silencing transcripts derived from genes that exhibit a herbicidal effect; or (2) polynucleotides, including but not limited to DNA, RNA and / or chemically modified nucleotides, which affect the amount of a specific target by down-regulating, interfering, inhibiting or silencing transcripts derived from genes that exhibit a safening effect.

[0840] Of note is a composition comprising a compound of the present invention (in a herbicidally effective amount), at least one additional active ingredient selected from the group consisting of other herbicides and herbicide safeners (in a herbicidally effective amount), and at least one component selected from the group consisting of surfactants, solid diluents and liquid diluents.

[0841] Table A1 lists specific combinations of components (a) and (b), illustrating mixtures, compositions and methods of the present invention. The compound number (Compound Number) in the component (a) column (i.e., compound 1) is identified in Index Table A. The second column of Table A1 lists specific component (b) compounds (e.g., "2,4-D" in the first row). The third, fourth and fifth columns of Table A1 list the weight ratio ranges (i.e., (a): (b)) at which component (a) compounds are typically applied to field-grown crops. Thus, for example, the first row of Table A1 specifically discloses that the combination of component (a) (i.e., compound 1 in Index Table A) and 2,4-D is typically applied in a weight ratio between 1:384–6:1. The remaining rows of Table A1 will be similarly constructed.

[0842] Table A1

[0843]

[0844]

[0845]

[0846]

[0847]

[0848]

[0849] Table A2 is constructed the same as Table A1 above, except that those entries under the "Component (a)" column heading are replaced by the corresponding component (a) column entries shown below. The compound numbers in the component (a) column are identified in Index Table A. Thus, for example, in Table A2, the entries under the "Component (a)" column heading all list "Compound 2" (i.e., Compound 2 identified in Index Table A), and the first row under the column heading in Table A2 specifically discloses a mixture of Compound 2 and 2,4-D. Tables A3 to A414 are similarly constructed.

[0850]

[0851]

[0852]

[0853]

[0854] Preferred for better control of undesirable vegetation (e.g., such as lower use rates from an enhanced effect, a wider range of controlled weeds or enhanced crop safety) or for preventing the development of resistant weeds are mixtures of a compound of the invention with a herbicide selected from the group consisting of chlorimuron-methyl, nicosulfuron-methyl, mesotrione, thifensulfuron-methyl, fluazifop-methyl, bensulfuron-methyl, roxasulfone, pinoxaden, cypermethrin, metolachlor, and S-metolachlor.

[0855] The following tests prove the control efficacy of the compounds of the present invention on specific weeds. However, the weed control provided by the compounds is not limited to these species. Compound descriptions refer to Index Tables A to F. The following abbreviations are used in the subsequent index tables: t is tertiary, s is secondary, n is positive, i is different, c is ring, Me is methyl, Et is ethyl, Pro is propyl, i-Pro is isopropyl, Bu is butyl, c-Pro is cyclopropyl, c-Bu is cyclobutyl, c-Pen is cyclopentyl, t-Bu is tert-butyl, i-Bu is isobutyl, s-Bu is sec-butyl, Ph is phenyl, OMe is methoxy, OEt is ethoxy, SMe is methylthio, SEt is ethylthio, -CN is cyano, -NO2 is nitro, TMS is trimethylsilyl, allyl is CH2CH=CH2, propargyl is CH2C≡CH and naphthyl (naphthyl) means naphthyl (naphthalenyl). Some other structures are defined in the following table.

[0856]

[0857] (1') or (1") indicates the absolute chirality (*) of the asymmetric carbon center. (1') and (1") are defined as follows.

[0858]

[0859] The abbreviation "(d)" indicates that the compound appears to decompose when melted. The abbreviation "Cmpd.#" stands for "Compound Number". The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound was prepared. + The molecular weight of the most isotopically abundant parent ion (M+1) added to the molecule (molecular weight 1) is reported with an estimated accuracy within ±0.5 Da.

[0860] Index Table A

[0861]

[0862]

[0863]

[0864] *(1') and (1") are defined as follows.

[0865]

[0866] Index Table B

[0867]

[0868] <![CDATA[ Cmpd# ]]> <![CDATA[ A ]]> <![CDATA[ R 1a ]]> <![CDATA[ R 1b ]]> <![CDATA[ R 3a ]]> <![CDATA[ R 4a ]]> <![CDATA[ MS ]]> <![CDATA[ MP(℃) ]]> 6 A-1 H H Et Cl 151.2–155.1 404 A-11 - 4-Me (1')-Me Cl 368

[0869] Index Table C

[0870]

[0871]

[0872]

[0873]

[0874]

[0875]

[0876]

[0877]

[0878]

[0879]

[0880] *(1′) and (1″) are defined as follows.

[0881]

[0882] Index Table D

[0883]

[0884] <![CDATA[ Cmpd# ]]> <![CDATA[ A ]]> <![CDATA[ R 1a ]]> <![CDATA[ R 1b ]]> <![CDATA[ R 1c ]]> <![CDATA[ R 2 ]]> <![CDATA[ R 3a ]]> <![CDATA[ R 4a ]]> <![CDATA[ MS ]]> 139 A-1 H H - H (1')-Me Cl 371 271 A-1 Et H - 6-OMe (1')-Me Me 409 362 A-1 Me H - 6-F (1')-Me Me 383

[0885] Index Table E

[0886]

[0887] <![CDATA[ Cmpd# ]]> <![CDATA[ A ]]> <![CDATA[ R 1a ]]> <![CDATA[ R 1b ]]> <![CDATA[ R 1c ]]> <![CDATA[ R 2 ]]> <![CDATA[ R 3a ]]> <![CDATA[ R 4a ]]> <![CDATA[ MS ]]> <![CDATA[ MP(℃) ]]> 305 A-1 i-Pro H - H (1')-Me Cl 399

[0888] Index Table F

[0889]

[0890]

[0891]

[0892] Biological Examples of the Invention

[0893] Test A

[0894] Seeds of plant species selected from the following were planted in a blend of loam and sand and treated pre-emergence with the test chemical formulated in a non-phytotoxic solvent mixture containing a surfactant by directed soil spraying: barnyard grass (Echinochloa crus-galli), blackgrass (Alopecurus myosuroides), corn (Zea mays), giant foxtail (Setaria faberi), goosegrass (Eleusine indica), Kochia (Bassiascoparia), wild oat (Avena fatua), palmer pigweed (Amaranthus palmeri), redroot pigweed (Amaranthus retroflexus), ragweed (Ambrosia artemisiifolia), Italian ryegrass (Lolium multiflorum), soybean (Glycine max), and wheat (Triticum aestivum).

[0895] At the same time, the plant selected from these crops and weed species and also Galium (Galiumaparine) and Erigeron canadensis are planted in the pot containing the same blend of fertile soil and sand, and the test chemicals prepared in the same way are used to carry out post-emergence treatment.For post-emergence treatment, the height range of plant is from 2 to 10cm and is in one leaf to two leaf stages. Treated plants and untreated controls are kept in greenhouse for 10 days, and all treated plants are compared with untreated controls afterwards and visual assessment is injured.The plant response rating that is summarized in Table A is based on a scale of 0 to 100, wherein 0 is no effect and 100 is complete control.Dash (-) response means no test result.

[0896]

[0897]

[0898]

[0899]

[0900]

[0901]

[0902]

[0903]

[0904]

[0905]

[0906]

[0907]

[0908]

[0909]

[0910]

[0911]

[0912]

[0913]

[0914] Test B

[0915] Plant species selected from the flooded paddy field test of barnyard grass (Echinochloa crus-galli), Heteranthera limosa (Heteranthera limosa), rice (Oryza sativa) and sedge (Cyperus difformis) were grown to the 2-leaf stage for testing. When processing, the test pot was submerged to 3 cm above the soil surface, processed by directly applying the test compound to paddy water, and then remained on the depth of water during the test. Treated plants and controls were kept in greenhouse for 13 days, and all species were compared with controls and visually evaluated afterwards. The plant response rating summarized in Table B is based on a scale of 0 to 100, wherein 0 is no effect and 100 is complete control. The dash (-) response means no test result.

[0916]

[0917]

[0918] Test C

[0919] Seeds of plant species selected from the following were planted in a blend of loam and sand and treated pre-emergence with the test chemical formulated in a non-phytotoxic solvent mixture containing a surfactant by directed soil spraying: barnyard grass (Echinochloa crus-galli), black grass (Alopecurus myosuroides), corn (Zea mays), giant foxtail (Setaria faberi), green foxtail (Setaria viridis), goosegrass (Eleusine indica), Kochia (Bassia scoparia), wild oat (Avena fatua), palmer pigweed (Amaranthus palmeri), redroot pigweed (Amaranthus retroflexus), ragweed (Common ragweed, Ambrosia artemisiifolia), Italian ryegrass (Allium ryegrass, Lolium multiflorum), soybean (Glycine max) and wheat (Triticum aestivum).

[0920] At the same time, the plant selected from these crops and weed species and also Galium (Galiumaparine) and Erigeron canadensis are planted in the pot containing the same blend of fertile soil and sand, and the test chemicals prepared in the same way are used to carry out post-emergence treatment.For post-emergence treatment, the height range of plant is from 2 to 10cm and is in one leaf to two leaf stages. Treated plants and untreated controls are kept in greenhouse for 10 days, and all treated plants are compared with untreated controls afterwards and visual assessment is injured.The plant response rating that is summarized in Table C is based on a scale of 0 to 100, wherein 0 is no effect and 100 is complete control.Dash (-) response means no test result.

[0921]

[0922]

[0923]

[0924]

[0925]

[0926]

[0927]

[0928]

[0929]

[0930]

[0931]

[0932]

[0933]

[0934]

[0935]

[0936]

[0937]

[0938]

[0939]

[0940]

[0941]

[0942]

[0943]

[0944]

[0945]

[0946]

[0947]

[0948]

[0949]

[0950] Test D

[0951] Plant species selected from the flooded paddy field test of barnyard grass (Echinochloa crus-galli), Heteranthera limosa (Heteranthera limosa), rice (Oryza sativa) and cyperus (Cyperus difformis) were grown to the 2-leaf stage for testing. When processing, the test pot was submerged to 3 cm above the soil surface, and the test compound was directly applied to paddy field water for processing, and then remained on the depth of water during the test. Treated plants and controls were kept in greenhouse for 13 to 14 days, and all species were compared with controls and visually evaluated afterwards. The plant response rating summarized in Table D is based on a scale of 0 to 100, wherein 0 is no effect and 100 is complete control. The dash (-) response means no test result.

[0952]

[0953]

[0954]

[0955]

Claims

1. A compound of formula 1, all stereoisomers, N-oxides and salts thereof in A is a 5- or 6-membered heterocyclic ring containing ring members selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S and up to 4 N atoms, one or two carbon or sulfur ring members of the heterocyclic ring may be optionally in the oxidized form of a carbonyl, sulfonyl, sulfinyl moiety, the ring being bonded to the rest of Formula 1 via a carbon atom or heteroatom and optionally substituted by 1 to 4 R 1 replace; R 1 Independently R 1a , (R 1b ) m or R 1c or any combination thereof; R 1a is H, halogen, cyano, nitro, amino, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C3–C7 alkyloxacycloalkyl, C2–C6 thiacycloalkyl, C3–C7 thiacycloalkylalkyl, C3–C7 alkylthiacycloalkyl, C2–C6(O- C3–C7(O-thia)cycloalkylalkyl, C3–C7alkyl(O-thia)cycloalkyl, C2–C6(O2thia)cycloalkyl, C3–C7(O2thia)cycloalkylalkyl, C3–C7alkyl(O2thia)cycloalkyl, C2–C6haloalkenyl, C2–C6haloalkynyl, C3–C7halocycloalkyl, C4–C7haloalkylcycloalkyl, C2–C7alkoxyalkyl, C2–C7haloalkoxyalkyl, C1–C7alkoxy, C2–C5alkenyloxy, C2–C5alkynyloxy, C3–C7cycloalkyloxy, C4–C7cycloalkyloxyalkyl, C1–C7haloalkoxy, C1–C7 C7 alkylthio, C2–C7 alkylthioalkyl, C1–C5 alkylsulfinyl, C1–C5 alkylsulfonyl, C1–C4 alkylsulfonate, C1–C5 haloalkylthio, C1–C5 haloalkylsulfinyl, C1–C5 haloalkylsulfonyl, C2–C7 alkylsulfinylalkyl, C2–C7 alkylsulfonylalkyl, C2–C7 haloalkylthioalkyl, C2–C7 haloalkylsulfinylalkyl, C2–C7 haloalkylsulfonylalkyl, C2–C7 alkylthiocycloalkyl, C4–C7 alkylsulfinylcycloalkyl, C4–C7 alkylsulfonylcycloalkyl, C4–C7 haloalkylthiocycloalkyl, C2–C7 halo or phenyl, optionally substituted with up to 3 substituents independently selected from the group consisting of halogen, cyano, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy and C1-C2 haloalkoxy; R 1b is H, halogen, cyano, nitro, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C3–C5 halocycloalkyl, C2–C4 alkoxyalkyl, C1–C4 alkoxy, C1–C4 alkylthio, or C2–C4 alkoxycarbonyl; m is 0, 1, or 2; R 1c is H, C1–C7 alkyl, C3–C7 cycloalkyl or C1–C7 haloalkyl; X 1 and X 2 Independently N or CR 2 ; n is 0, 1, 2, or 3; Each R 2 are independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1 – C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 alkylsulfonate, C3–C5 cycloalkylsulfonate, C1–C4 haloalkylsulfonate, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, C2–C5 cyanoalkyl, C4–C6 cyanocycloalkyl, or C2–C5 alkoxycarbonyl; or Two adjacent R 2 may together form a saturated or unsaturated 5- to 8-membered ring containing carbon atoms and optionally 1 to 3 oxygen, sulfur or nitrogen atoms as ring members, one or two carbon or sulfur ring members of the heterocyclic ring may optionally be in oxidized form of a carbonyl, sulfonyl, sulfinyl moiety, the ring being unsubstituted or substituted with at least one substituent independently selected from the group consisting of halogen, cyano, nitro, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy and C1-C4 haloalkoxy; Y is O or S; R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C2–C7 alkylthioalkyl, C2–C7 alkylthioalkyl, Sulfonylalkyl, C2–C7 alkylsulfonylalkyl, C2–C7 haloalkylthioalkyl, C2–C7 haloalkylsulfinylalkyl, C2–C7 haloalkylsulfonylalkyl, C2–C5 cyanoalkyl, C4–C6 cyanocycloalkyl, C1–C4 nitroalkyl, C3–C6 alkylcarbonylalkyl, C2–C6 oxacycloalkyl, C2–C6 oxacycloalkylalkyl, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, or C3–C6 alkoxycarbonylalkyl; Each R 3b are independently H, halogen or C1-C3 alkyl; or; R 3a and R 3b together with the carbon atoms to which they are attached form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from 1 oxygen atom, 1 sulfur atom and up to 3 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring members are selected from S, S(O) or S(O)2; or Two R's 3b together with the carbon atoms to which they are attached form a 3- to 7-membered ring containing ring members selected from carbon atoms and up to 3 heteroatoms independently selected from 1 oxygen atom, 1 sulfur atom and up to 3 nitrogen atoms, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring member is selected from S, S(O) or S(O)2; p is 0, 1, 2, or 3; R 4a is H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, C5–C8 trialkylsilylalkynyl, C1–C5 alkylthio, C1–C5 haloalkylthio, or C2–C5 alkoxycarbonyl; q is 0, 1, or 2; Each R 4b are independently H, halogen, cyano, nitro, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 alkylthio; Provided that the compound of formula 1 is not: [3-(5-Cyclopropyl-1,2,4-oxadiazol-3-yl)phenyl](2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-methanone (CAS Reg. No. 1798020-19-5); (8-Chloro-2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[3-(1H-tetrazol-1-yl)phenyl]methanone (CAS Reg. No. 2093742-48-2); (2-Ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 1808378-56-4); (8-Chloro-2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 1808849-41-3); (2,3-Dihydro-2,7-dimethyl-4H-1,4-benzoxazin-4-yl)[2-(1H-1,2,4-triazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 1436224-65-5); (8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[2-(1H-pyrazol-1-yl)-4-pyridinyl]-methanone (CAS Reg. No. 2224006-86-2); (2,3-Dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1-pyrrolidinyl)phenyl]methanone (CAS Reg. No. 2733463-68-6); Methanone, (3,4-dihydrospiro[2H-1,4-benzoxazin-2,1′-cyclopropane]-4-yl)[3-(1-pyrrolidinyl)phenyl] (CAS Reg. No. 2733410-16-5); (2,3-Dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1H-pyrrol-1-yl)phenyl]methanone (CAS Reg. No. 2305402-15-5); (3,4-dihydrospiro[2H-1,4-benzoxazine-2,1′-cyclopropane]-4-yl)[3-(1H-pyrrol-1-yl)phenyl]methanone (CAS Reg. No. 2305290-36-0); (8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-[5-(methoxymethyl)-1,3,4-oxadiazol-2-yl]phenyl]methanone (CAS Reg. No. 2223792-20-7); (7-Fluoro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[2-(4-methyl-1-piperazinyl)-4-pyridinyl]methanone (CAS Reg. No. 2212440-53-2); (7-Fluoro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1H-1,2,4-triazol-5-yl)phenyl]methanone (CAS Reg. No. 2094921-82-9); (2-Ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1957585-10-2); (8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1957541-06-8); (8-Chloro-2-ethyl-2,3-dihydro-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1956163-57-7); (2,3-Dihydro-2,6-dimethyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1955383-94-4); (2,3-Dihydro-2,2-dimethyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1955104-90-1); (6-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1954398-26-5); (2,3-Dihydro-6-methoxy-2-methyl-4H-1,4-benzoxazin-4-yl)[5-(4-morpholinyl)-3-pyridinyl]methanone (CAS Reg. No. 1947266-43-4); and (2,3-Dihydro-6-methoxy-2-methyl-4H-1,4-benzoxazin-4-yl)[3-(1H-imidazol-1-yl)phenyl]methanone (CAS Reg. No. 1384688-76-9).

2. The compound according to claim 1, wherein A is selected from 3. The compound according to claim 1, wherein A is A-1, A-4, A-5, A-12, A-14, A-15 or A-17.

4. The compound according to claim 3, wherein A is A-1.

5. The compound according to claim 4, wherein X 1 and X 2 Both are CR 2 ; R 1a is H, halogen, cyano, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl , C3–C7 oxacycloalkylalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkoxy, C4–C7 cycloalkoxyalkyl, or C1–C7 haloalkoxy; R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C3–C5 halocycloalkyl, C2–C4 alkoxyalkyl, C1–C4 alkoxy, or C2–C4 alkoxycarbonyl; R 2 R is independently H, halogen, cyano, nitro, hydroxy, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C1–C5 alkylthio, C1–C4 alkylsulfinyl, C1–C4 alkylsulfonyl, C1–C4 alkylsulfonate, C1–C4 haloalkylthio, C1–C4 haloalkylsulfinyl, C1–C4 haloalkylsulfonyl, or C2–C5 alkoxycarbonyl; or R 2 Together they may form a 5- or 6-membered ring containing up to 2 oxygen atoms as ring members; R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C2–C7 alkylthioalkyl, C2–C7 haloalkylthioalkyl, C2–C5 cyanoalkyl, C1–C4 nitroalkyl, C3–C6 alkylcarbonylalkyl, C2–C6 oxacycloalkyl, C3–C7 cycloalkyloxy, or C3–C6 alkoxycarbonylalkyl; R 3b is H or halogen; R 4a is H, halogen, cyano, nitro, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, C3–C6 trialkylsilyl, or C5–C8 trialkylsilylalkynyl; R 4b is H, halogen, cyano, nitro, C1–C4 alkyl, C1–C4 haloalkyl, C1–C4 alkoxy, or C1–C4 alkylthio.

6. The compound according to claim 5, wherein R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C7 haloalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 oxacycloalkylalkyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, C2–C7 haloalkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, or C1–C7 haloalkoxy; R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl; R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C2–C5 alkenyloxy, C2–C5 alkynyloxy, C3–C7 cycloalkyloxy, C4–C7 cycloalkyloxyalkyl, C3–C6 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C5 haloalkyl, C2–C5 haloalkenyl, C2–C5 haloalkynyl, C2–C5 alkoxyalkyl, C2–C5 haloalkoxyalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy; R 3a is halogen, C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C2–C6 haloalkenyl, C2–C6 haloalkynyl, C3–C7 halocycloalkyl, C4–C7 haloalkylcycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl; R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and R 4b It is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy.

7. The compound according to claim 6, wherein R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C1–C6 hydroxyalkyl, C3–C7 hydroxycycloalkyl, C1–C6 hydroxyhaloalkyl, C4–C8 alkoxycycloalkyl, C2–C7 alkoxyhaloalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkyloxyalkyl; R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl; R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy; R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl; and R 4b is H or halogen.

8. The compound according to claim 7, wherein R 1a is H, Me, Et, i-Pro, i-Bu, Bu, t-Bu, Br, cyano, c-Bu, c-Pen, c-Hex, HOCH2, HOC(Me)2, CH2OMe, CH2O-i-Pro, CH2CH2OMe, CH2-c-Hex or 3-oxetanyl; R 1b is H, Me, i-Pro, CN, CF3, F or Cl; R 2 is independently H, OH, CN, OEt, propargyl, allyl, c-Pro, F, Cl, Br, CN, Me, Et, OMe, CF3, OCF3 or CH2CF3; R 3a is Me, Et, Pro, i-Pro, CF3, CH2F or CH2OMe; and R 4a It is H, CN, NO2, F, Cl, Br, Me, Et, CF3, CH2F, OCF3, OMe, CH2OMe, CH=CH2, C≡CSiMe3, C≡CH or c-Pro.

9. The compound according to claim 4, wherein X 1 is N and X 2 Yes CR 2 ; R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl; R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl; R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy; R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl; R 3b is H or halogen; R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and R 4b is H or halogen.

10. The compound according to claim 9, wherein R 1a It is H; R 1b It is H; R 2 are independently H, C1-C5 alkyl or C1-C5 alkoxy; R 3a is C1–C7 alkyl, C3–C7 cycloalkyl, C1–C7 haloalkyl or C2–C7 alkoxyalkyl; R 3b is H or halogen; R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; R 4b It is H, halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl or C1-C4 alkoxy.

11. The compound according to claim 4, wherein X 1 Yes CR 2 And X 2 is N; R 1a is H, halogen, cyano, C1–C7 alkyl, C3–C7 cycloalkyl, C4–C7 cycloalkylalkyl, C2–C6 oxacycloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, C1–C7 alkoxy, C3–C7 cycloalkyloxy, or C4–C7 cycloalkoxyalkyl; R 1b is H, halogen, cyano, C1–C4 alkyl, C3–C5 cycloalkyl, C1–C4 haloalkyl, C2–C4 alkoxyalkyl, or C2–C4 alkoxycarbonyl; R 2 are independently H, halogen, cyano, OH, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C6 cycloalkyl, C1–C5 haloalkyl, C1–C5 alkoxy, or C1–C5 haloalkoxy; R 3a is C1–C7 alkyl, C2–C6 alkenyl, C2–C6 alkynyl, C3–C7 cycloalkyl, C1–C7 alkoxy, C4–C7 cycloalkylalkyl, C4–C7 alkylcycloalkyl, C1–C7 haloalkyl, C3–C7 halocycloalkyl, C2–C7 alkoxyalkyl, or C2–C7 haloalkoxyalkyl; R 3b is H or halogen; R 4a is H, halogen, cyano, NO2, C1–C5 alkyl, C2–C5 alkenyl, C2–C5 alkynyl, C3–C5 cycloalkyl, C1–C5 alkoxy, C1–C5 haloalkoxy, or C5–C8 trialkylsilylalkynyl; and R 4b is H or halogen.

12. The compound according to claim 4, wherein R 2 Together they may form a 5- or 6-membered ring containing up to 2 oxygen atoms as ring members.

13. The compound of claim 1, selected from the group consisting of: [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methyl-5-[3-(1-methylethyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone; [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-[3-(1,1-dimethylethyl)-1H-1,2,4-triazol-1-yl]-2-methylphenyl]methanone; [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-methoxy-5-[3-(1-methylethyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone; [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-(3-ethyl-1H-1,2,4-triazol-1-yl)-2-methoxyphenyl]methanone; [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][2-ethyl-5-[3-(1-methylethyl)-1H-1,2,4-triazol-1-yl]phenyl]methanone; [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][5-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)-2-methylphenyl]methanone; [(2S)-8-Chloro-2,3-dihydro-2-methyl-4H-1,4-benzoxazin-4-yl][3-(3-cyclobutyl-1H-1,2,4-triazol-1-yl)phenyl]methanone; [(2S)-2,3-Dihydro-2,8-dimethyl-4H-1,4-benzoxazin-4-yl][2-methoxy-5-(1H-1,2,4-triazol-1-yl)phenyl]methanone; as well as 14. A herbicidal composition comprising the compound according to claim 1 and at least one component selected from the group consisting of a surfactant, a solid diluent and a liquid diluent.

15. A herbicidal composition comprising the compound according to claim 1, at least one additional active ingredient selected from the group consisting of other herbicides and herbicide safeners, and at least one component selected from the group consisting of surfactants, solid diluents and liquid diluents.

16. A herbicidal mixture comprising (a) a compound as claimed in claim 1 and (b) at least one additional active ingredient selected from the group consisting of: (b1) a photosystem II inhibitor, (b2) an acetohydroxyacid synthase (AHAS) inhibitor, (b3) an acetyl-CoA carboxylase (ACCase) inhibitor, (b4) an auxin mimetic, (b5) an inhibitor of 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase, (b6) a photosystem I electron diverter, (b7) a protoporphyrinogen oxidase (PPO) inhibitor, (b8) a glutamine synthetase (GS) inhibitor, (b9) a very long chain fatty acid (VLCFA) elongase inhibitor, (b10) an auxin transporter transport inhibitors, (b11) phytoene dehydrogenase (PDS) inhibitors, (b12) 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibitors, (b13) homogentisate solanesyl transferase (HST) inhibitors, (b14) cellulose biosynthesis inhibitors, (b16) other herbicides, including mitotic disruptors, organic arsenic compounds, sulfamethoxam, bromobutyric acid, cyproconazole, benzylpyruvate, dazomethane, difenac, cyproconazole, ethoxybencarb, cyprodinil, phosphine, phosphine-ammonium, hydantoin, methamphetamine, methyl phosphine, oleic acid, oxazolidinone, nonanoic acid and cyproconazole, (b16) herbicide safeners, and salts of the compounds of (b1) to (b16).

17. A method for controlling the growth of undesirable vegetation comprising contacting the vegetation or its environment with a herbicidally effective amount of a compound as claimed in claim 1.

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