Process for the preparation of substituted enamines

Abstract

The presently claimed invention is directed to a process for the preparation of substituted enamines which are versatile intermediates for the production of photostabilizers.

Description

[0001] Process for the preparation of substituted enamines

[0002] Technical field

[0003] The presently claimed invention is directed to a process for the preparation of substituted enamines which are versatile intermediates for the production of photostabilizers.

[0004] Summary of the invention

[0005] UV-light absorbing filters require stabilization by one or more compounds or materials in the formulation. In order to increase the photostability of said photo-unstable UV-filters the combined use with a photostabilizer is suggested. For example, an increase in photostability of avobenzone can be observed when it is combined with zinc oxide or avobenzone’s photostability can be enhanced by addition of octocrylene or phenylbenzimidazole sulfonic acid.

[0006] However, the use of some of the photostabilizers is controversial. For example, octocrylene and benzophenones has been recently incriminated to potentially induce adverse effects on the endocrine system in addition to having allergic and / or photoallergic potential and might be harmful to corals.

[0007] Mycosporine-like amino acid compounds with enamine functionality were identified as compounds that stabilize a photo-unstable UV-filter against the degradative effects of UV irradiation or enhance the UV-absorbing properties of a photo-unstable UV-absorbing compound. These compounds are described in PCT / EP2023 / 071804.

[0008] WO 2023 / 279205 A1 describes a process for the preparation of enamines which involves the use of large amounts of toxic and dangerous chemicals such as phosphorous oxychloride and its handling on process scale arises serious safety concerns. The processes of the prior art suffer from several drawbacks such as high effluent load, use of non-benign solvents and toxic reagents, low yields, low selectivity, and limited flexibility to introduce different functionalities.

[0009] Hence, it is an object of the presently claimed invention to overcome these disadvantages and provide a flexible and modular process for the synthesis of enamines which can easily be upscaled to an industrial scale process with high yield and high selectivity, avoids the use of non-benign solvents and toxic reagents and is safe, easily controllable and energyefficient.

[0010] The object was solved by the subject matter of the independent patent claims. Further aspects of the present invention are however also apparent from the wording of the dependent patent claims, the following detailed description in conjunction with the accompanying examples and figures.

[0011] Summary of the invention

[0012] In one aspect, the presently claimed invention is directed to a process for the preparation of substituted enamines of general formula (III),

[0013] (HI), wherein

[0014] R1 is selected from the group consisting of CH2, unsubstituted or substituted CH(alkyl), unsubstituted or substituted C(alkyl)2, unsubstituted or substituted CH(cycloalkyl), unsubstituted or substituted CH(aryl), unsubstituted or substituted CH(heterocycloalkyl), unsubstituted or substituted CH(heteroaryl), -CR7R8 , C=O, halogen, 0, S, SO, SO2, NH, unsubstituted or substituted N(alkyl), unsubstituted or substituted N(alkenyl), unsubstituted or substituted N(alkynyl), unsubstituted or substituted N(alkoxy), unsubstituted or substituted N(alkylthio), unsubstituted or substituted N(cycloalkyl), unsubstituted or substituted N(aryl), unsubstituted or substituted N(heterocycloalkyl), unsubstituted or substituted N(heteroaryl), and unsubstituted or substituted C- spirocycles;

[0015] R4, R5 and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, -CH2-OH, -R-CH2-OH, -C(=O)-O-W, -R-C(=O)-O-W, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, SO, SO2, -S(=O)2OH, sulfonyl, NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstituted or substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), and unsubstituted or substituted NH(heteroaryl), unsubstituted or substituted NR9R10, and unsubstituted or substituted C-spirocycles;

[0016] R7 and R8 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, -CH2-OH, -R-CH2-OH, -C(=O)-O-W, -R-C(=O)-O-W, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, SO, SO2, NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstituted or substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), unsubstituted or substituted NH(heteroaryl) and unsubstituted or substituted NR9R10 ; W is selected from the group consisting of H and unsubstituted or substituted alkyl; and R is unsubstituted or substituted alkyl or alkylene; and R9 und R10 which may be identical or different, are independently from each other selected from the group consisting of H, OH, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocylcoalkyl, and unsubstituted or substituted heteroaryl; comprising at least the step of

[0017] (A) reacting at least one compound of general formula (I),

[0018] (I), optionally in the form of its salts, hydrates and / or solvates, wherein R4, R5 and R6 are defined as above and below; with at least one compound of general formula (II),

[0019] (II), wherein R1 is defined as above and below; to obtain a compound of general formula (III),

[0020] (HI), wherein R1 , R4, R5 and R6 are defined as above and below.

[0021] In another aspect, the presently claimed invention is directed to the preparation of substituted enamines of general formula (VI),

[0022] (VI), wherein

[0023] R1 , R4, R5, and R6, are defined as above and below;

[0024] A is S; R2 is -C(=O)-O-W; and

[0025] W is selected from the group consisting of H and unsubstituted or substituted alkyl; comprising at least the steps of

[0026] (A) reacting at least one compound of general formula (I),

[0027] (I), optionally in the form of its salts, hydrates and / or solvates, wherein R4, R5 and R6 are defined as above and below; with at least one compound of general formula (II),

[0028] (II), wherein R1 is defined as above and below; to obtain a compound of general formula (III),

[0029] (Ill), wherein R1 , R4, R5 and R6 are defined as above and below; and

[0030] (B1 ) reacting at least one compound of general formula (III), with at least one halogenating agent to obtain a compound of general formula (IV);

[0031] (IV), wherein R1 , R4, R5 and R6 are defined as above and below and Y is Cl, Br or I, and (C1 ) reacting at least one compound of general formula (IV) with at least one compound of general formula (VII),

[0032] (VII), optionally in the form of its salts, hydrates and / or solvates, wherein R2 is defined as above and below; to obtain a compound of general formula (VI).

[0033] In another aspect, the presently claimed invention is directed to the preparation of substituted enamines of general formula (X), wherein R1 , R4, R5 and R6 are defined as above and below and Z is defined as above and below; comprising at least the steps of

[0034] (A) reacting at least one compound of general formula (I), optionally in the form of its salts, hydrates and / or solvates, wherein R4, R5 and R6 are defined as above and below; with at least one compound of general formula (II), wherein R1 is defined as above and below; to obtain a compound of general formula (HI), wherein R1 , R4, R5 and R6 are defined as above and below; and

[0035] (C2) reacting at least one compound of general formula (III) with at least one compound of general formula (XI),

[0036] (XI), optionally in the form of its salts, hydrates and / or solvates, wherein Z is defined as above and below, to obtain a compound of general formula (X).

[0037] The process of the presently claimed invention is associated with at least one of the following advantages:

[0038] • The process of the presently claimed invention allows for the flexible and modular synthesis of compounds of general formula (VI) and (X) with a wide array of different functionalities and high functional group tolerance.

[0039] • The process of the presently claimed invention can be easily upscaled to an industrial scale process with high yield and high selectivity.

[0040] • The process of the presently claimed invention can be carried out in benign solvents.

[0041] • The process of the presently claimed invention is energy-efficient because it is carried out at relatively low temperatures.

[0042] • All steps of the presently claimed invention can be sequentially carried out in one pot which saves process steps of purification and separation.

[0043] • The process of the presently claimed invention produces a low effluent load.

[0044] • The process of the presently claimed invention is safe and can be easily controlled.

[0045] Detailed description of the invention In the context of the presently claimed invention, the following general meanings apply:

[0046] As used herein, the singular form “a”, “a” and “the” include plural references unless the context clearly dictates otherwise. Thus, for example reference to “cosmetic preparation”, “the cosmetic preparation” or “a cosmetic preparation” also includes a plurality of cosmetic preparations.

[0047] The terms “comprising”, “including”, and “containing” are to be understood as open- ended terms and mean that the named components following said term are essential but not “limited to”, and other components may be added and are still embraced by the presently claimed invention.

[0048] The term “consisting of’ as used according to the presently claimed invention means that the total amount of components (a) and (b) adds up to 100 % by weight, based on the total weight of the sunscreen product or cosmetic or pharmaceutical preparation, and signifies that the subject matter is closed-ended and can only include the limitations that are expressly recited.

[0049] Whenever reference is made to “comprising” it is intended to cover both meanings as alternatives, that is the meaning can be either “comprising” or “consisting of” unless the context dictates otherwise.

[0050] The term “optionally” means that the subsequently described compound may but need not to be present in the composition, and that the description includes embodiments, where the compound is included or embodiments, where the compound is absent.

[0051] The term "or" or "and / or" is used as a function word to indicate that two words or phrases are to be taken together or separately.

[0052] The endpoints of all ranges directed to the same component or property are inclusive and independently combinable. The compounds may be identified by either their chemical structure and / or chemical name. When the chemical structure and chemical name are in conflict, the chemical structure determines the identity of the compound.

[0053] In general, the term “salts” denotes the salts of those cations or the acid addition salts of those acids whose cations and anions, respectively, do not have any adverse effect on the action of the compounds according to the present invention. Suitable cations are in particular the ions of the alkali metals, preferably lithium, sodium and potassium, of the alkaline earth metals, preferably calcium, magnesium and barium, and of the transition metals, preferably manganese, copper, zinc and iron, and also ammonium (NH4+) and substituted ammonium in which one to four of the hydrogen atoms are replaced by Ci- C4-alkyl, Ci-C4-hydroxyalkyl, Ci-C4-alkoxy, Ci-C4-alkoxy-Ci-C4-alkyl, hydroxy-Ci-C4- alkoxy-Ci-C4-alkyl, phenyl or benzyl. Examples of substituted ammonium ions comprise methylammonium, isopropylammonium, dimethylammonium, diisopropylammonium, trimethylammonium, tetramethylammonium, tetraethylammonium, tetrabutylammonium, 2-hydroxyethylammonium, 2-(2-hydroxyethoxy)ethyl-ammonium, bis(2- hydroxyethyl)ammonium, benzyltrimethylammonium and benzyltriethylammonium, furthermore phosphonium ions, sulfonium ions, preferably tri(Ci-C4-alkyl)sulfonium, and sulfoxonium ions, preferably tri(Ci-C4-alkyl)sulfoxonium. Anions of useful acid addition salts are primarily chloride, bromide, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, phosphate, nitrate, hydrogen carbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and the anions of Ci-C4-alkanoic acids, preferably formate, acetate, propionate and butyrate.

[0054] The term “solvate” denotes a co-complex of the compounds according to the invention, or a stereoisomer, salt, tautomer or N-oxide thereof, with solvent molecules. The solvent is usually liquid. Examples of solvents are methanol, ethanol, toluol, xylol. A preferred solvent which forms solvates is water, which solvates are referred to as “hydrates”. A solvate or hydrate is usually characterized by the presence of a fixed number of n molecules solvent per m molecules compound according to the invention.

[0055] In one aspect, the presently claimed invention is directed to a process for the preparation of substituted enamines of general formula (III),

[0056]

[0057] (III), wherein

[0058] R1 is selected from the group consisting of CH2, unsubstituted or substituted CH(alkyl), unsubstituted or substituted C(alky 1)2, unsubstituted or substituted CH(cycloalkyl), unsubstituted or substituted CH(aryl), unsubstituted or substituted CH(heterocycloalkyl), unsubstituted or substituted CH(heteroaryl), -CR7R8 , C=O, halogen, 0, S, SO, SO2, NH, unsubstituted or substituted N(alkyl), unsubstituted or substituted N(alkenyl), unsubstituted or substituted N(alkynyl), unsubstituted or substituted N(alkoxy), unsubstituted or substituted N (alky Ithio), unsubstituted or substituted N(cycloalkyl), unsubstituted or substituted N(aryl), unsubstituted or substituted N(heterocycloalkyl), unsubstituted or substituted N(heteroaryl), and unsubstituted or substituted C- spirocycles;

[0059] R4, R5 and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=0)-, -CH2-OH, -R-CH2-OH, -C(=0)-0-W, -R-C(=0)-0-W, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, SO, SO2, - S(=0)20H, sulfonyl, NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstituted or substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), and unsubstituted or substituted NH(heteroaryl), unsubstituted or substituted NR9R10, and unsubstituted or substituted C-spirocycles; R7 and R8 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, -CH2-OH, -R-CH2-OH, -C(=O)-O-W, -R-C(=O)-O-W, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, SO, SO2, NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstituted or substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), unsubstituted or substituted NH(heteroaryl) and unsubstituted or substituted NR9R10 ; W is selected from the group consisting of H and unsubstituted or substituted alkyl; and R is unsubstituted or substituted alkyl or alkylene; and

[0060] R9 und R10 which may be identical or different, are independently from each other selected from the group consisting of H, OH, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocylcoalkyl, and unsubstituted or substituted heteroaryl; comprising at least the step of

[0061] (A) reacting at least one compound of general formula (I),

[0062] (I), optionally in the form of its salts, hydrates and / or solvates, wherein R4, R5 and R6 are defined as above and below; with at least one compound of general formula (II),

[0063] (II), wherein R1 is defined as above and below; to obtain a compound of general formula

[0064] (HI),

[0065] (HI), wherein R1 , R4, R5 and R6 are defined as above and below.

[0066] The term “halogen” residue / moiety or group alone or as part of another substituent according to the presently claimed invention refers to F, Cl, Br or I.

[0067] The term "alkyl" alone or as part of another substituent according to the presently claimed invention refers to a saturated or mono- or polyunsaturated linear or branched monovalent hydrocarbon radical obtained by removing a hydrogen atom from a single carbon atom of a corresponding parent alkane.

[0068] In a preferred variation, the term "alkyl" also includes any alkyl moieties in radicals derived therefrom, such as alkoxy, alkylthio, alkylsulfonyl saturated linear or branched hydrocarbon radicals having 1 to 10, 1 to 8, 1 to 6, or 1 to 4 carbon atoms.

[0069] If the alkyl radical is further bonded to another atom, it becomes an alkylene radical or alkylene group. In other words, the term "alkylene" also refers to a divalent linear or branched alkyl. For example, -CH2CH3 is an ethyl, while -CH2CH2- is an ethylene. The term "alkylene" alone or as part of another substituent refers to a saturated linear or branched divalent hydrocarbon radical obtained by removing two hydrogen atoms from a single carbon atom or two different carbon atoms of a starting alkane.

[0070] In preferred embodiments according to the presently claimed invention, the linear or branched alkyl group or alkylene group comprises 1 to 10 carbon atoms. In other still more preferred embodiments, the linear or branched alkyl group or alkylene group comprises 1 to 6 carbon atoms.

[0071] More preferred according to the presently claimed invention are saturated linear or branched C1 to C6 alkyl groups or saturated linear or branched C1 to C6 alkylene groups.

[0072] Most preferred are the linear or branched alkyl groups or alkylene groups with 1 to 4 carbon atoms.

[0073] Preferred alkyl radicals / moieties or alkyl groups include, but are not limited to: C1 to C6 alkyl comprising methyl, ethyl, propyl, 1 -methylethyl, butyl, 1 -methylpropyl, 2- methylpropyl, 1 ,1 -dimethylethyl, pentyl, 1 -methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2- dimethylpropyl, 1 -ethylpropyl, hexyl, 1 ,1 -dimethylpropyl, 1 ,2-dimethylpropyl, 1- methylpentyl, 2- methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 ,1 -dimethylbutyl, 1 ,2- dimethylbutyl, 1 ,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 -ethylbutyl, 2 -ethylbutyl, 1 ,1 ,2-trimethylpropyl, 1 ,2,2-trimethylpropyl, 1 -ethyl-1 - methylpropyl and 1-ethyl-2-methylpropyl.

[0074] In a preferred embodiment, the alkyl radical / moiety is methyl, ethyl, propyl, isopropyl, butyl, isobutyl or tert-butyl, more preferred form the group consisting of methyl and ethyl.

[0075] The alkyl group or alkylene group as defined above may further be substituted.

[0076] The term "alkyl" or "alkylene" further includes radicals or groups having any degree of saturation, i.e. , groups having only single carbon-carbon bonds ("alkyl" or "alkylene"), groups having one or more double carbon-carbon bonds ("alkenyl"), radicals having one or more triple carbon-carbon bonds ("alkynyl"), and groups having a mixture of single, double and / or triple carbon-carbon bonds.

[0077] The term "alkenyl" alone or as part of another substituent according to the presently claimed invention refers to an unsaturated linear or branched monovalent hydrocarbon radical having at least one carbon-carbon double bond (C=C double bond). The radical may be in either the cis or trans conformation around the double bond(s). So that the term "alkenyl" also includes the corresponding cis / trans isomers.

[0078] In preferred embodiments according to the presently claimed invention, the linear or branched alkenyl group comprises 2 to 10 carbon atoms. In other preferred embodiments, the linear or branched alkenyl group comprises 2 to 6 carbon atoms.

[0079] In still further preferred embodiments, the linear or branched alkenyl group comprises 2 to 4 carbon atoms.

[0080] Preferred according to the presently claimed invention are mono- or di-unsaturated linear or branched C1 to C6 alkenyl groups.

[0081] Typical alkenyl radicals or alkenyl groups include, but are not limited to, ethenyl; propenyls such as prop-1 -en-1-yl, prop-1 -en-2-yl, prop-2-en-1 -yl (allyl), prop-2-en-2-yl, cycloprop-1-en-1-yl, cycloprop-2-en-1-yl; butenyls such as but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1 ,3-dien-1-yl, buta-1 ,3-dien-2- yl and the like.

[0082] The alkenyl group as defined above may further be substituted.

[0083] The term "alkynyl" alone or as part of another substituent according to the presently claimed invention refers to an unsaturated linear or branched monovalent hydrocarbon radical having at least one carbon-carbon triple bond (C=C triple bond). In preferred embodiments according to the presently claimed invention, the linear or branched alkynyl group comprises 2 to 10 carbon atoms. In other preferred embodiments, the alkynyl group comprises 2 to 6 carbon atoms. In still further preferred embodiments, the alkynyl group comprises 2 to 4 carbon atoms.

[0084] Most preferred according to the presently claimed invention are mono- or di-unsaturated linear or branched C1 to C6 alkynyl groups.

[0085] Typical alkynyl radicals / moieties or alkynyl groups include, but are not limited to, ethynyl; propynyls such as prop-1 -yn-1-yl, prop-2-in-1 -yl, etc.; butynyls such as but-1-in- 1-yl, but-1 -in-3-yl, but-3-in-1 -yl, and the like.

[0086] The alkynyl group as defined above may further be substituted. The alkyl group or alkylene group as defined above may further be substituted.

[0087] The term "alkoxy" alone or as part of another substituent according to the presently claimed invention refers to a linear or branched radical of the formula -O-R, where R is alkyl or substituted alkyl, as defined herein.

[0088] In preferred embodiments according to the presently claimed invention, the linear or branched alkoxy group comprises 2 to 10 carbon atoms. In other preferred embodiments, the linear or branched alkoxy group comprises 2 to 6 carbon atoms. In still further preferred embodiments, the linear or branched alkoxy group comprises 2 to 4 carbon atoms.

[0089] Most preferred according to the presently claimed invention are linear or branched C1 to C6 alkoxy groups.

[0090] Typical alkoxy radicals / moieties or alkoxy groups include C1 to C6 alkoxy comprising C1 to C4 alkoxy such as. methoxy, ethoxy, n-propoxy, 1 -methylethoxy, butoxy, 1- methylpropoxy, 2-methylpropoxy or 1 ,1 -dimethylethoxy; as well as pentoxy, 1- methylbutoxy, 2-methylbutoxy, 3-methylbutoxy, 1 ,1 -dimethylpropoxy, 1 ,2- dimethylpropoxy, 2,2-dimethylpropoxy, 1 -ethylpropoxy, hexoxy, 1 -methylpentoxy, 2- methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1 ,1 -dimethylbutoxy, 1 ,2- dimethylbutoxy, 1 ,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3- dimethylbutoxy, 1 -ethylbutoxy, 2-ethylbutoxy, 1 ,1 ,2-trimethylpropoxy, 1 ,2,2- trimethylpropoxy, 1 -ethyl-1 -methylpropoxy or 1-ethyl-2-methylpropoxy.

[0091] In a preferred embodiment, the alkoxy radical or alkoxy group is methoxy (-O-methyl), ethoxy (-O-ethyl), propoxy (-O-propyl) or butoxy (-O-butyl), more preferred from the group consisting of methoxy (-O-methyl) and ethoxy (-O-ethyl).

[0092] The alkoxy group or alkylene group as defined above may further be substituted.

[0093] The term "alkylthio" or "thioalkoxy" alone or as part of another substituent according to the presently claimed invention refers to a radical of the formula -S-R, wherein R is alkyl or substituted alkyl, as defined herein.

[0094] According to the presently claimed invention, the term "alkyl" or "alkylene" also includes heteroalkyl radicals or heteroalkyl groups. The term "heteroalkyl" by itself or as part of other substituents refers to alkyl groups in which one or more of the carbon atom(s) is / are independently replaced by the same or another heteroatom or by the same or another heteroatomic group(s). Typical heteroatoms or heteroatomic groups that may replace the carbon atoms include, but are not limited to, -O-, -S-, -N-, -Si-, - NH-, -S(O)-, -S(O)2-, -S(O)NH-, -S(O)2NH-, and the like, and combinations thereof. The heteroatoms or heteroatomic groups may be located at any internal position of the alkyl group.

[0095] Typical heteroatomic groups that may be included in these groups include, but are not limited to, -O-, -S-, -O-O-, -S-S-, -O-S-, -NRR-, =NN=, -N=N-, -N=N-NRR, -PR-, -P(O)2- -POR-, -O-P(O)2-, -SO-, -SO2-, -SR2OR-, and the like, wherein R is independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl as defined herein. The alkyl group or alkylene group as defined above may further be substituted.

[0096] The term "acyl" or “alkanoyl” alone or as part of another substituent according to the presently claimed invention refers to a radical R-C(=O)-, wherein R is hydrogen, unsubstituted or substituted alkyl, unsubstituted substituted cycloalkyl, unsubstituted or substituted aryl, arylalkyl, unsubstituted or substituted arylalkyl, unsubstituted or substituted heteroalkyl, unsubstituted or substituted heteroarylalkyl, as defined herein.

[0097] Representative examples include, but are not limited to, formyl, acetyl, propionyl, butyryl, valeryl, benzoyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzylcarbonyl, and the like.

[0098] The term "cycloalkyl" alone or as part of another substituent according to the presently claimed invention refers to a saturated or mono- or polyunsaturated, non-aromatic, cyclic monovalent hydrocarbon radical in which the carbon atoms are ring-linked and which has no heteroatom.

[0099] The carbon ring can occur as a monocyclic compound, which has only a single ring, or as a polycyclic compound, which has two or more rings.

[0100] In one preferred variation, the term "cycloalkyl" includes a three- to ten-membered monocyclic cycloalkyl radical or cycloalkyl group or a nine- to twelve-membered polycyclic cycloalkyl radical or cycloalkyl group. In other still more preferred embodiments, the cycloalkyl moiety comprises a five-, six- or seven-membered monocyclic cycloalkyl moiety or a nine- to twelve-membered bicyclic cycloalkyl moiety.

[0101] In a preferred embodiment according to the presently claimed invention, a cycloalkyl radical or group comprises 3 to 20 carbon atoms. In an even more preferred embodiment, a cycloalkyl radical comprises 6 to 15 carbon atoms. In a most preferred embodiment, a cycloalkyl radical comprises 6 to 10 carbon atoms. Most preferred are monocyclic C3 to C7 cycloalkyl groups. Typical cycloalkyl radicals or cycloalkyl groups include, but are not limited to, saturated carbocyclic radicals having 3 to 20 carbon atoms, such as C3 to C12 carbocyclyl, comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, and cyclododecyl; cyclopentyl, cyclohexyl, cycloheptyl, as well as cyclopropyl-methyl, cyclopropyl-ethyl, cyclobutyl-methyl, cyclobutyl-ethyl, cyclopentyl-methyl, cyclopentyl-ethyl, cyclohexyl-methyl, or C3- to C7- carbocyclyl comprising cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopropyl-methyl, cyclopropyl-ethyl, cyclobutyl-methyl, cyclopentyl-ethyl, cyclohexyl- methyl, cyclobut-1-en-1-yl, cyclobut-1-en-3-yl, ,3-dien-1-yl and the like.

[0102] Polycyclic cycloalkyl radicals or cycloalkyl groups preferred according to the presently claimed invention include but are not limited to naphthyl, indenyl, groups and the like.

[0103] According to the presently claimed invention, the term "cycloalkyl" also includes cycloalkenyls, i.e. unsaturated cyclic hydrocarbon radicals containing C=C double bonds between two carbon atoms of the ring molecule. In a broader sense, cycloalkenyls are compounds with one, two or more double bond(s), where the number of possible, mostly conjugated double bonds in the molecule depends on the ring size.

[0104] Typical cycloalkenyls include, but are not limited to, cyclopropenyl, cyclopentenyl, cyclohexenyl, cyclopentadienyl, and the like.

[0105] According to the presently claimed invention, the term "cycloalkyl" further includes cycloalkynyls, i.e. unsaturated, -C=C-triple bonds, containing cyclic hydrocarbon radicals between two carbon atoms of the ring molecule, the triple bond depending on the ring size for reasons of ring tension. Typical cycloalkynyles include cyclooctin.

[0106] The cycloalkyl, cycloalkenyl or cycloalkynyl moieties or groups, as defined above or below, may further be substituted. The term "aryl" alone or as part of another substituent according to the presently claimed invention refers to a monovalent aromatic hydrocarbon radical derived by removing a hydrogen atom from a single carbon atom of an aromatic ring system.

[0107] In one preferred variation, the term "aryl" includes a three- to ten-membered monocyclic aryl radical or aryl group or a nine- to twelve-membered polycyclic aryl radical or aryl group. In other still more preferred embodiments, the carboaryl radical comprises a five- , six- or seven-membered monocyclic carboaryl radical or a nine- to twelve-membered bicyclic carboaryl radical.

[0108] In a preferred embodiment according to the presently claimed invention, the aryl radical comprises 3 to 20 carbon atoms. In a preferred variation, the aryl moiety comprises 6 to 15 ring atoms. In an even more preferred embodiment, an aryl radical comprises 6 to 10 carbon atoms.

[0109] Most preferred according to the presently claimed invention are monocyclic C3 to C10 aryl groups. Most preferred are monocyclic C3 to C7 aryl groups.

[0110] Typical aryl radicals include, without being limited thereto, benzene, phenyl, biphenyl, naphthyl such as 1- or 2-naphthyl, tetrahydronaphthyl, fluorenyl, indenyl, and phenanthrenyl. Typical carboaryl moieties further include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, corone, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as-indacene, S-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene and the like.

[0111] Aromatic polycyclic aryl radicals or aryl groups preferred according to the presently claimed invention include, but are not limited to, naphthalene, biphenyl, and the like.

[0112] The aryl moiety or group, as defined above or below, may further be substituted. The term "arylalkyl" alone or as part of another substituent according to the presently claimed invention refers to an acyclic alkyl group in which one of the hydrogen atoms attached to a carbon atom, typically a terminal or sp carbon atom, is replaced by an aryl group as defined herein. In other words, arylalkyl may also be considered as alkyl substituted by aryl. Typical arylalkyl groups include, but are not limited to, benzyl, 2- phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl, 2-naphthylethan-1-yl, 2- naphthylethen-1-yl, naphthobenzyl, 2-naphthophenylethan-1-yl, and the like.

[0113] The term "heteroarylalkyl" alone or as part of another substituent refers to a cyclic alkyl group in which one of the hydrogen atoms attached to a carbon atom is replaced by a heteroaryl group.

[0114] In a preferred embodiment according to the presently claimed invention, the heteroarylalkyl group is a 6- to 20-membered heteroarylalkyl, e.g., the alkyl, alkenyl, or alkynyl group of the heteroarylalkyl is a C1- to C6-alkyl and the heteroaryl group is a 5- to 15-membered heteroaryl group. In other embodiments, the heteroarylalkyl is a 6- to 13-membered heteroarylalkyl, e.g., the alkyl, alkenyl, or alkynyl group is a C1- to C3- alkyl and the heteroaryl group is a 5 to 10-membered heteroaryl.

[0115] The term "heterocycloalkyl" alone or as part of another substituent according to the presently claimed invention refers to a saturated or mono- or polyunsaturated, nonaromatic, cyclic monovalent hydrocarbon radical in which one or more carbon atom(s) is / are independently replaced by the same or a different heteroatom. Typical heteroatoms to replace the carbon atom(s) include, but are not limited to, N, P, 0, S, Si, etc. Typical heterocycloalkyl groups include, without being limited thereto, groups derived from epoxides, azirines, thiiranes, imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidone, quinuclidine and the like.

[0116] In a preferred embodiment according to the presently claimed invention, the heterocycloalkyl moiety or group comprises 3 to 20 ring atoms. In a preferred variation, the heterocycloalkyl moiety comprises 6 to 15 ring atoms. In an even more preferred embodiment, the heterocycloalkyl moiety comprises 6 to 10 carbon atoms. The heterocycloalkyl moiety can occur as a monocyclic compound, which has only a single ring, or as a polycyclic compound, which has two or more rings, such as bicyclic, tricyclic or spirocyclic.

[0117] Preferably, the term "heterocycloalkyl" includes three- to seven-membered, saturated or mono- or polyunsaturated heterocycloalkyl moieties comprising one, two, three or four heteroatoms selected from the group consisting of 0, N and S. The heteroatom or heteroatoms may occupy any position in the heterocycloalkyl ring.

[0118] In one preferred variation, the term "heterocycloalkyl" includes a three- to tenmembered monocyclic heterocycloalkyl radical or a nine- to twelve-membered polycyclic heterocycloalkyl radical. In other still more preferred embodiments, the heterocycloalkyl moiety comprises a five-, six- or seven-membered monocyclic heterocycloalkyl moiety or a nine- to twelve-membered bicyclic heterocycloalkyl moiety.

[0119] Most preferred according to the presently claimed invention are monocyclic heterocycloalkyl radicals comprising 3 to 12 carbon atoms. Most preferred are monocyclic heterocycloalkyl radicals having 5 to 7 ring atoms.

[0120] Typical heterocycloalkyl moieties include, but are not limited to: Five- or six-membered, saturated or monounsaturated heterocycloalkyl containing one or two nitrogen atoms and / or one oxygen or sulfur atom or one or two oxygen and / or sulfur atoms as ring members comprising 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3- tetrahydrothienyl, 1 -pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, 3-lsoxazolidinyl, 4- Isoxazolidinyl, 5-lsoxazolidinyl, 3-lsothiazolidinyl, 4-lsothiazolidinyl, 5-lsothiazolidinyl, 3- pyrazolidinyl, 4-pyrazolidinyl, 5-pyrazolidinyl, 2-oxazolidinyl, 4-oxazolidinyl, 5- oxazolidinyl, 2-thiazolidinyl, 4-thiazolidinyl, 5-thiazolidinyl, 2-lmidazolidinyl, 4- Imidazolidinyl, 2-pyrrolin-2-yl, 2-pyrrolin-3-yl, 3-pyrrolin-2-yl, 3-pyrrolin-3-yl, 1 -piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1 ,3-dioxan-5-yl, 2-tetrahydropyranyl, 4- tetrahydropyranyl, 2-tetrahydrothienyl, 3-hexahydropyridazinyl, 4-hexahydropyridazinyl, 2-hexahydropyrimidinyl, 4-hexahydropyrimidinyl, 5-hexahydropyrimidinyl, 2-piperazinyl and the like.

[0121] The heterocycloalkyl moiety or group, as defined above or below, may further be substituted.

[0122] The term "heteroaryl" by itself or as part of another substituent according to the presently claimed invention refers to a monovalent heteroaromatic radical obtained by removing a hydrogen atom from a single atom of a heteroaromatic ring SY-stem.

[0123] Typical heteroaryl radicals, or. Heteroaryl groups include, but are not limited to, those derived from acridine, [3-carboline, chroman, chromium, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromium, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazole, xanthene and the like are derived.

[0124] The heteroaryl moiety can occur as a monocyclic compound having only a single ring or as a polycyclic compound having two or more rings.

[0125] In one preferred variation, the term "heteroaryl" includes a three- to ten-membered monocyclic heteroaryl radical or a nine- to twelve-membered polycyclic heteroaryl radical. In other still more preferred embodiments, the heteroaryl moiety comprises a five-, six- or seven-membered monocyclic heteroaryl moiety or a nine- to twelvemembered bicyclic heteroaryl moiety.

[0126] Preferably, the term "heteroaryl" includes three- to seven-membered monocyclic heteroaryl radicals comprising one, two, three or four heteroatoms selected from the group consisting of 0, N and S. The heteroatom or heteroatoms may occupy any position in the heteroaryl ring. In a preferred embodiment according to the presently claimed invention, the heteroaryl moiety or group comprises 3 to 20 ring atoms. In an even more preferred embodiment, the heteroaryl moiety comprises 6 to 15 ring atoms. In a most preferred embodiment, the heteroaryl group comprises 6 to 10 ring atoms. Most preferred according to the presently claimed invention are monocyclic C3 to C7 heteroaryl groups.

[0127] Particularly preferred heteroaryl moieties or heteroaryl groups include, but are not limited to, those derived from furan, thiophene, pyrrole, benzothiophene, benzofuran, benzimidazole, indole, pyridine, pyrazole, quinoline, imidazole, oxazole, isoxazole, and pyrazine.

[0128] Five-membered aromatic heteroaryl radicals containing, in addition to carbon atoms, one, two or three nitrogen atoms or one or two nitrogen atoms and one sulfur or oxygen atom as ring atoms include 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3- pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4- thiazolyl, 5-thiazolyl, 2-lmidazolyl, 4-lmidazolyl, and 1 ,3,4-triazol-2-yl.

[0129] Five-membered aromatic heteroaryl radicals containing one, two, three or four nitrogen atoms as ring atoms include 1 -, 2- or 3-pyrrolyl, 1 -, 3- or 4-pyrazolyl, 1 -, 2- or 4- Imidazolyl, 1 ,2,3-[1 H]-triazol-1 -yl, 1 ,2,3-[2H]-triazol-2-yl, 1 ,2,3-[1 H]-triazol-4-yl, 1 ,2,3- [1 H]-triazol-5-yl, 1 ,2, 3-[2H]-triazol-4-y I, 1 ,2,4-[1 H]-triazol-1 -yl, 1 ,2,4-[1 H]-triazol-3-yl, 1 , 2,4-[ 1 H]-triazol-5-y 1 , 1 , 2, 4-[4H]-triazol-4-y 1 , 1 , 2,4-[4H]-triazol-3-y I , [1 H]-tetrazol-1 -yl, [1 H]-tetrazol-5-yl, [2H]-tetrazol-2-yl, [2H]-tetrazol-5-yl and the like.

[0130] Five-membered aromatic heteroaryl radicals containing a heteroatom selected from oxygen or sulfur and optionally one, two or three nitrogen atoms as ring atoms include 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 3- or 4-lsoxazolyl, 3- or 4-isoth iazoly I, 2-, 4- or 5- oxazolyl, 2-, 4- or 5-thiazolyl, 1 ,2,4-thiadiazol-3-yl, 1 ,2,4-thiadiazol-5-yl, 1 ,3,4-thiadiazol- 2-yl, 1 ,2,4-oxadiazol-3-yl, 1 ,2,4-oxadiazol-5-yl and 1 ,3,4-oxadiazol-2-yl.

[0131] Six-membered heteroaryl radicals containing, in addition to carbon atoms, one or two or one, two or three nitrogen atoms as ring atoms, and comprising, for example. 2- pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1 ,2,4-triazin-3-yl; 1 ,2,4-triazin-5-yl, 1 ,2,4-triazin-6-yl and 1 ,3,5- triazin-2-yl.

[0132] The heteroaryl moiety or group, as defined above or below, may further be substituted.

[0133] The term “C-spirocycles” in the context of the present application means compounds that have at least two molecular rings with only one common atom. The simplest spiro compounds are bicyclic (having just two rings) or have a bicyclic portion as part of the larger ring system, in either case with the two rings connected through the defining single common atom. The one common atom connecting the participating rings distinguishes spiro compounds from other bicyclic structures: from isolated ring compounds like biphenyl that have no connecting atoms, from fused ring compounds like decalin having two rings linked by two adjacent atoms, and from bridged ring compounds like norbornane with two rings linked by two non-adjacent atoms. Spiro compounds may be fully carbocyclic (all carbon) or heterocyclic (having one or more non-carbon atom, such as N, 0 and S). The common atom that connects the two (or sometimes three) rings is called the spiro atom. Preferably, the spiro atom is a carbon atom. More preferably, the C-spirocycles compound means compounds that are fully carbocyclic (all carbon).

[0134] The term "substituted" in the context of the presently claimed invention means that one or more hydrogen atoms of the indicated radical or group is / are independently replaced by the same or a different substituent(s). Additionally, the term "substituted" specifically provides for one or more, i.e. , two, three, or even more, substitutions commonly used in the art. However, it is generally known that the substituents should be selected so that they do not adversely affect the useful properties of the compound or its function.

[0135] Suitable substituents in the context of the presently claimed invention preferably include halogen, perfluoroalkyl groups, perfluoroalkoxy groups, alkyl groups, alkenyl groups, alkynyl groups, hydroxy groups, oxo groups, mercapto groups, alkylthio groups, alkoxy groups, aryl or heteroaryl groups, aryloxy groups or heteroaryloxy groups, arylalkyl or heteroarylalkyl groups, arylalkoxy or heteroarylalkoxy groups, amino groups, alkyl and dialkylamino groups, carbamoyl groups, alkylcarbonyl groups, carboxyl groups, alkoxycarbonyl groups, alkylaminocarbonyl groups, dialkylaminocarbonyl groups, arylcarbonyl groups, aryloxycarbonyl groups, alkylsulfonyl groups, arylsulfonyl groups, cycloalkyl groups, cyano groups, C1 to C6 alkylthio groups, arylthio groups, nitro groups, keto groups, acyl groups, boronate or boronyl groups, phosphate or phosphonyl groups, sulfamyl groups, sulfonyl groups, sulfinyl groups, and combinations thereof.

[0136] Substituents or substituent groups useful for substituting saturated carbon atoms in the indicated group or radical more preferably include, but are not limited to, halogen, hydroxyl, alkyl, alkenyl, alkynyl, alkoxyl, -NH2, amino (primary, secondary, or tertiary), nitro, thiol, thioether, imine, cyano, amido, phosphonato, phosphine, carboxyl, thiocarbonyl, sulfonyl, sulfonamide, ketone, aldehyde, ester, acetyl, acetoxy, carbamoyl, oxygen (0); haloalkyl (e.g., trifluoromethyl); aminoacyl and aminoalkyl, carbocyclic cycloalkyl, which may be monocyclic or fused or non-fused polycyclic (e.g., cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl), or a heterocycloalkyl, which may be monocyclic or fused or non-fused polycyclic (e.g. pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, or thiazinyl), carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic aryl (e.g., phenyl, naphthyl, pyrrolyl, indolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, triazolyl, tetrazolyl, pyrazolyl, pyridinyl, quinolinyl, isoquinolinyl, acridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, benzimidazolyl, benzothiophenyl, or benzofuranyl), -CO2CH3, -CONH2, -OCH2CONH2; -SO2NH2, -OCHF2, -CF3, -OCF3.

[0137] According to the presently claimed invention, the substituents used to replace a particular radical or radical may in turn be further substituted, typically with one or more of the same or different radicals selected from the various groups indicated above and as defined in detail above. In the case of substituted combinations such as substituted arylalkyl, either the aryl or the alkyl group may be substituted, or both the aryl and the alkyl group may be substituted with one or more substituents.

[0138] In a preferred embodiment, R1 in the compounds of general formulae (II), (III), (IV), (VI) and (X) is selected from the group consisting of CH2, C(alkyl)2, CH(alkyl), 0, S, SO, S02, NH and N(alkyl), more preferably R1 is selected from the group consisting of CH2 and C(methyl)2. Most preferably, the compound of general formula (II) is selected from the group consisting of cyclopentane-1 ,3-dione, cyclohexan-1 ,3-dione, and dimedone (5,5-dimethyl-cyclohexane-1 ,3-dione).

[0139] In a preferred embodiment, in the compounds of general formulae (I), (III), (IV), (VI) and (X) R4, R5 and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, alkyl, preferably methyl, ethyl, propyl, iso-propyl, butyl, isobutyl or tert-butyl, alkoxy, preferably O-methyl, O-ethyl, or O-butyl, - S(=O)2OH, and sulfonyl. More preferably, the compound of general formula (I) is selected from the group consisting of methyl aniline, ethyl aniline, propyl aniline, isopropyl aniline, butyl aniline, isobutyl aniline, tert-butyl aniline, methoxy aniline, ethoxy aniline, butoxy aniline, hydroxy aniline, sulfanilic acid, dimethyl aniline, diethyl aniline, dipropyl aniline, diisopropyl aniline, dibutyl aniline, diisobutyl aniline, di-tert-butyl aniline, dimethoxy aniline, diethoxy aniline, dibutoxy aniline, methyl ethyl aniline, methyl methoxy aniline, ethyl ethoxy aniline, methyl hydroxy aniline, ethyl sulfanilic aniline, trimethyl aniline, triethyl aniline, tripropyl aniline, triisopropyl aniline, tributyl aniline, triisobutyl aniline, tri-tert-butyl aniline, trimethoxy aniline, triethoxy aniline, tributoxy aniline, preferably the compound of general formula (I) is selected from the group consisting of dimethoxy aniline, diethoxy aniline, and dibutoxy aniline.

[0140] In a preferred embodiment, step (A) is carried out during a period in the range of > 1 h to < 24 h, more preferably in the range of > 1 h to < 12 h, even more preferably in the range of > 1 h to < 6 h. In a preferred embodiment, step (A) is carried out at a temperature in the range of > 30°C to < 100°C, more preferably in the range of > 35°C to < 90°C.

[0141] In a preferred embodiment, step (A) is carried out in the presence of at least one acid which is selected from the group consisting of inorganic acids, and organic sulfonic acids. More preferably, the inorganic acids are selected from the group consisting of sulfuric acid, hydrochloric acid, phosphoric acid, perchloric acid, nitric acid, nitrous acid, sulfurous acid, chloric acid, chlorous acid and hypochlorous acid. More preferably, the organic sulfonic acids are selected from the group consisting of methane sulfonic acid, trifluoromethane sulfonic acid, trichloromethane sulfonic acid and p-toluene sulfonic acid.

[0142] In a preferred embodiment, step (A) is carried out in the presence of at least one protic polar solvent. More preferably, the at least one protic polar solvent is an alcohol selected from the group consisting of 2-methylbutan-2-ol, benzyl alcohol, 1 ,4- butanediol, 1 ,2,4-butanetriol, 2-butanol, 1 -butanol, 2-methylpropan-1-ol, 2- methylpropan-2-ol, methanol, 2-(2-methoxyethoxy)ethanol, 2-methyl-1 -butanol, 2- methyl-1 -pentanol, 3-methyl-2-butanol, diethylene glycol, ethanol, ethylene glycol, 2- ethylhexanol, furfuryl alcohol, glycerol, propan-2-ol, neopentyl alcohol, 2-pentanol, 1 ,3- propanediol, 1 -propanol and propylene glycol; most preferably the at least one protic polar solvent is an alcohol selected from the group consisting of methanol, ethanol, and isopropanol.

[0143] In a preferred embodiment, step (A) is carried out in the presence of at least one aromatic solvent. More preferably, the at least one aromatic solvent is selected from the group consisting of toluene, xylene, cymene and mono-chlorobenzene.

[0144] In a preferred embodiment, the compound of general formula (II) and the compound of general formula (I) are reacted in a molar ratio of > 0.9: 1.0 to < 1.1 : 1.0, more preferably in a ratio of 1.0: 1.0. In a preferred embodiment, the compound of general formula (II) is present in a concentration of > 1 .0 mol / L to < 2.5 mol / L, preferably in the range of > 1 .3 mol / L to < 2.0 mol / L. In a preferred embodiment, the compound of general formula (I) is present in a concentration of > 1 .0 mol / L to < 2.5 mol / L, preferably in the range of > 1 .3 mol / L to < 2.0 mol / L.

[0145] The presently claimed invention is also directed to a process for the preparation of substituted enamines of general formula (VI),

[0146] (IV), wherein R1 , R4, R5 and R6 are defined as above in general formula (III) and Y is Cl, Br or I; comprising at least the step of

[0147] (B1 ) reacting at least one compound of general formula (III),

[0148] (HI), wherein R1 , R4, R5 and R6 are defined as above in general formula (III). with at least one halogenating agent to obtain a compound of general formula (IV), to obtain a compound of general formula (IV).

[0149] In a preferred embodiment, step (B1 ) is carried out for a period in the range of > 1 h to < 24 h, more preferably in the range of > 1 h to < 12 h, even more preferably in the range of > 1 h to < 6 h. In a preferred embodiment, step (B1 ) is carried out in a temperature in the range of > 0°C to < 20°C, more preferably in the range of > 10°C to < 18°C.

[0150] In a preferred embodiment, in case Y is Cl in the compound of general formula (IV), the at least one halogenating agent is a chlorinating agent selected from N- chlorosuccinimide and dichloroisocyanuric acid; in case Y in the compound of general formula (IV) is Br, the at least one halogenating agent is a brominating agent selected from the group consisting of KBr, N-bromosuccinimide or Br2 and in case Y is I, the at least one halogenating agent is a iodinating agent selected from the group consisting of KI, N-iodosuccinimide and I2. In a preferred embodiment, the at least one halogenating agent is added dropwise or in small portions.

[0151] In a preferred embodiment, step (B1 ) is carried out in the presence of at least one protic polar solvent. More preferably, the at least one protic polar solvent is an alcohol selected from the group consisting of 2-methylbutan-2-ol, benzyl alcohol, 1 ,4- butanediol, 1 ,2,4-butanetriol, 2-butanol, 1 -butanol, 2-methylpropan-1-ol, 2- methylpropan-2-ol, methanol, 2-(2-methoxyethoxy)ethanol, 2-methyl-1 -butanol, 2- methyl-1 -pentanol, 3-methyl-2-butanol, diethylene glycol, ethanol, ethylene glycol, 2- ethylhexanol, furfuryl alcohol, glycerol, propan-2-ol, neopentyl alcohol, 2-pentanol, 1 ,3- propanediol, 1 -propanol and propylene glycol; most preferably the at least one protic polar solvent is an alcohol selected from the group consisting of methanol, ethanol, and isopropanol.

[0152] In a preferred embodiment, the at least one solvent in step (A) is identical to the at least one solvent in step (B1). In a preferred embodiment, steps (A) and (B1 ) are carried out in a one-pot reaction and the at least one solvent is at least one protic polar solvent.

[0153] In a preferred embodiment, the ratio of the compound of general formula (III) to the at least one halogenating agent is in the range of > 1 .0: 1 .0 to < 1 .0: 1 .1. In a preferred embodiment, the at least one compound of general formula (III) is present at a concentration in the range of > 0.5 mol / L to < 0.9 mol / L.

[0154] In another aspect, the presently claimed invention is also directed to a compound of general formula (IVa), (IVa), wherein

[0155] R1 is selected from the group consisting of CH2, unsubstituted or substituted CH(alkyl), and unsubstituted or substituted C(alkyl)2;

[0156] R5 is selected from the group consisting of OH, ethyl, propyl, iso-propyl, butyl, isobutyl, tert-butyl, unsubstituted or substituted alkoxy, SO, SO2, -S(=O)2OH, and sulfonyl;

[0157] R4, and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, -CH2-OH, -R-CH2-OH, -C(=O)-O-W, -R-C(=O)-O-W, SO, SO2, - S(=O)2OH, and sulfonyl;

[0158] W is selected from the group consisting of H and unsubstituted or substituted alkyl;

[0159] R is unsubstituted or substituted alkyl or alkylene; and

[0160] Y is CI, Br or l; with the proviso that compounds, wherein R1 is C(methyl)2, R5 is O-methyl, R4 is H and R6 is H, and Y is Cl, Br or I, are excluded.

[0161] In a preferred embodiment, R1 is selected from the group consisting of CH2 and C(methyl)2. In a preferred embodiment, R5 is selected from the group consisting of OH, ethyl, propyl, iso-propyl, butyl, isobutyl, tert-butyl, O-methyl, O-ethyl, O-butyl, - S(=O)2OH, and sulfonyl. In a preferred embodiment, R4, and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, methyl, ethyl, propyl, iso-propyl, butyl, isobutyl, tert-butyl, O-methyl, O-ethyl, 0- butyl, -S(=0)20H, and sulfonyl. In a preferred embodiment, wherein n is 1.

[0162] More preferably the compound of general formula (IVa) is 2-bromo-3-(3,4-dimethoxyanilino)-5,5-dimethyl-cyclohex-2-en-1 -one

[0163]

[0164] The presently claimed invention is also directed to a process for the preparation of substituted enamines of general formula (VI),

[0165] (VI), wherein

[0166] R1 , R4, R5, and R6, are defined as above in general formula (III);

[0167] A is S; R2 is -C(=O)-O-W; and W is selected from the group consisting of H and unsubstituted or substituted alkyl; comprising at least the step of

[0168] (C1 ) reacting at least one compound of general formula (IV),

[0169] (IV),

[0170] R1 , R4, R5, and R6, are defined as above and below, with at least one compound of general formula (VII),

[0171] (VII), optionally in the form of its salts, hydrates and / or solvates, wherein R2 is defined as above in general formula (VI), to obtain a compound of general formula (VI).

[0172] In a preferred embodiment, step (C1 ) is carried out during a period in the range of > 1 h to < 12 h, more preferably in the range of > 1 h to < 10 h, even more preferably in the range of > 4 h to < 9 h. In a preferred embodiment, step (C1 ) is carried out at a temperature in the range of > 60°C to < 100°C, more preferably in the range of > 70°C to < 90°C.

[0173] In a preferred embodiment, step (C1 ) is carried out in the presence of at least one protic polar solvent. More preferably, the at least one protic polar solvent is an alcohol selected from the group consisting of 2-methylbutan-2-ol, benzyl alcohol, 1 ,4- butanediol, 1 ,2,4-butanetriol, 2-butanol, 1 -butanol, 2-methylpropan-1-ol, 2- methylpropan-2-ol, methanol, 2-(2-methoxyethoxy)ethanol, 2-methyl-1 -butanol, 2- methyl-1 -pentanol, 3-methyl-2-butanol, diethylene glycol, ethanol, ethylene glycol, 2- ethylhexanol, furfuryl alcohol, glycerol, propan-2-ol, neopentyl alcohol, 2-pentanol, 1 ,3- propanediol, 1 -propanol and propylene glycol; most preferably the at least one protic polar solvent is an alcohol selected from the group consisting of methanol, ethanol, and isopropanol.

[0174] In a preferred embodiment, the compound of general formula (IV) and the compound of general formula (VI) are reacted in a molar ratio of > 1.0: 1.0 to < 1.0: 1.4, more preferably in a ratio of > 1.0: 1.0 to < 1.1 : 1.3. In a preferred embodiment, steps (A), (B1 ) and (C1 ) are carried out in a one-pot reaction and the at least one solvent is at least one protic polar solvent.

[0175] In a preferred embodiment, step (C1 ) is carried out in the presence of at least one base which is selected from the group consisting of inorganic bases and organic bases. Preferably, the inorganic base is selected from the group consisting of alkali metal hydroxide, alkaline earth hydroxide, alkali metal bicarbonate, alkaline earth bicarbonate, alkali metal carbonate, alkaline earth carbonate, alkali metal phosphate, alkali metal alkoxide and alkaline earth alkoxide. More preferably, the alkali metal hydroxide is selected from group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide and cesium hydroxide; wherein alkaline earth hydroxide is selected from the group consisting of magnesium hydroxide, calcium hydroxide, strontium hydroxide and barium hydroxide; wherein alkali metal bicarbonate is selected from the group consisting of lithium bicarbonate, sodium bicarbonate, potassium bicarbonate, rubidium bicarbonate and cesium bicarbonate; wherein alkaline earth bicarbonate is selected from the group consisting of magnesium bicarbonate, calcium bicarbonate, strontium bicarbonate and barium bicarbonate; wherein alkali metal carbonate is selected from the group consisting of lithium carbonate, sodium carbonate, potassium carbonate, rubidium carbonate and cesium carbonate; wherein alkaline earth carbonate is selected from group the consisting of magnesium carbonate, calcium carbonate, strontium carbonate and barium carbonate; wherein alkali metal phosphate is selected from the group consisting of monosodium phosphate, disodium phosphate, trisodium phosphate, monopotassium phosphate, dipotassium phosphate and tripotassium phosphate; wherein alkali metal alkoxide is selected from the group consisting of NaOR27, KOR27, RbOR27and CsOR27; wherein alkaline earth alkoxide is selected from the group consisting of Mg(OR27)2, Ca(OR27)2 and Ba(OR27)2; whereby R27is, identical or different, Ci-C4-alkyl. Preferably, the organic base is selected from the group consisting of N(R26)s, N-methyl piperidine, N-methyl pyrrolidine, N-methyl morpholine, piperidine, dimethyl amino pyridine, pyridine, and tetra-Ci-Ce-alkyl ammonium hydroxide, wherein R26is, identical or different, hydrogen, Ci-Ce-alkyl, Cs- Ci4-aryl, or Cs-Ce-cycloalkyl.

[0176] The presently claimed invention is also directed to a process for the preparation of substituted enamines of general formula (X),

[0177] (X), wherein R1 , R4, R5 and R6 are defined as above in general formula (III) and Z is selected from the group consisting of O-R11 or amide’;

[0178] R11 is selected from the group consisting of H, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl; amide’ is selected from the group consisting of NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstituted or substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), unsubstituted or substituted NH(heteroaryl), and unsubstituted or substituted NR9’R10’, unsubstituted or substituted -N(O-alkyl)(alkyl) (Weinreb amide), -N(OH)(H) (hydroxamate), and unsubstituted or substituted -N(OH)(alkyl) (alkylated hydroxamate); comprising at least the step of

[0179] (C2) reacting at least one compound of general formula (III),

[0180] (HI), wherein R1 , R4, R5 and R6 are defined as above in general formula (III), with at least one compound of general formula (XI),

[0181] (XI), optionally in the form of its salts, hydrates and / or solvates, wherein Z is defined as above in general formula (X), to obtain a compound of general formula (X).

[0182] In a preferred embodiment,

[0183] R11 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, , , , (2-ethylhexyl) and phenyl; or amide’ is selected from the group consisting of NH2, NH(alkyl) and N(alkyl)2, -N(O- alkyl)(alkyl) (Weinreb amide) and -N(OH)(H) (hydroxamate.

[0184] In a preferred embodiment, steps (A), and (C2) are carried out in a one-pot reaction and the at least one solvent is at least one aromatic solvent.

[0185] In a preferred embodiment, step (C2) is carried out at a temperature in the range of > 50°C to < 100°C, more preferably in the range of > 60°C to < 90°C for a period in the range of > 1 h to < 12 h, preferably in the range of > 1 h to < 8 h, more preferably in the range of > 2 h to < 5 h, followed by a temperature in the range of > 100°C to < 120°C.

[0186] In a preferred embodiment, the presently claimed invention is directed to a compound of general formula (X) as defined above which is selected from the group consisting of 2- [(5,5-dimethyl-3-phenylimino-cyclohexen-1 -yl)amino]acetic acid, 2-[(3- phenyliminocyclohexen-1 -yl)amino]acetic acid, 2,5,5-trimethyl-3-(phenylimino)cyclohex- 1-en-1-yl-glycine, 2-[(2-methyl-3-phenylimino-cyclohexen-1-yl)amino]acetic acid, 3- ((3,4-dimethoxyphenyl)imino)-5,5-dimethylcyclohex-1 -en-1 -yl-g lycine, 3-((3,4- dimethoxyphenyl)imino)cyclohex-1 -en-1 -yl-g lycine, 3-((3,4-dimethoxyphenyl)imino)- 2.5.5-trimethy lcyclohex-1 -en-1 -yl-g lycine, 2-[(3-(3,4-dimethoxyphenyl)imino-2-methyl- cyclohexen-1 -yl)amino]acetic acid, 2-[(5,5-dimethyl-3-(4-sulfophenyl)imino-cyclohexen-

[0187] 1 -yl)amino]acetic acid, 2-[(3-(4-sulfophenyl)iminocyclohexen-1 -yl)amino]acetic acid,

[0188] 2.5.5-trimethyl-3-((4-sulfophenyl)imino)cyclohex-1 -en-1 -yl-g lycine, 2-methyl-3-((4- sulfophenyl)imino)cyclohex-1 -en-1 -yl-g lycine, 2-[(5,5-dimethyl-3-phenylimino- cyclohexen-1 -yl)amino]acetamide, 2-[(3-phenyliminocyclohexen-1 -yl)amino]acetamide,

[0189] 2-((2,5,5-trimethyl-3-(phenylimino)cyclohex-1 -en-1 -yl)amino)acetamide, 2-((2-methyl-3- (phenylimino)cyclohex-l -en-1 -yl)amino)acetamide, 2-((3-((3,4-dimethoxyphenyl)imino)-

[0190] 5.5-dimethylcyclohex-1-en-1 -yl)amino)acetamide, 2-[(3-(3,4- dimethoxyphenyl)iminocyclohexen-1 -yl)amino]acetamide, 2-((3-((3,4- dimethoxyphenyl)imino)-2,5,5-trimethylcyclohex-1 -en-1 -yl)amino)acetamide, and 2-((3- ((3,4-dimethoxyphenyl)imino)-2-methylcyclohex-1 -en-1-yl)amino)acetamide. In a preferred embodiment, the compound of general formula (X) as defined above is obtained by the process of the presently claimed invention as described above, in particular by a process comprising steps (A) and (C2).

[0191] Examples

[0192] The presently claimed invention is illustrated in detail by non-restrictive working examples which follow.

[0193] Methods

[0194] The characterization was by coupled High Performance Liquid Chromatography I mass spectrometry (HPLC / MS), Gas chromatography (GC), by NMR or by melting points.

[0195] 1H-NMR: The signals are characterized by chemical shift (ppm) vs. tetramethylsilane, by their multiplicity and by their integral (relative number of hydrogen atoms given). The following abbreviations are used to characterize the multiplicity of the signals: m = multiplet, q = quartet, t = triplet, d = doublet and s = singlet.

[0196] Example 1 : Synthesis of 3-(3,4-dimethoxyanilino)-5,5-dimethyl-cyclohex-2-en-1 -one

[0197] Dimedone (224 g, 1.60 mol, 1 equiv) and 3,4-dimethoxyanilin (250 g, 1.60 equiv, I .OO equiv) were added to ethanol (1250 g) under stirring. The resulting mixture was heated to 40 °C. When the solids have dissolved, methanesulfonic acid (15.4 g, 0.16 mol, 10 mol%) was added and the reaction was heated at 80 °C under reflux. After 5 hours, the reaction was cooled down to 10 °C and the precipitated solids were filtered off. The solid residue was washed with cold ethanol (20 g) and was dried at 50 °C overnight to yield the amide (368 g, 83%) analytically pure as a yellow solid. GC Ret. Index (DB-1 ): 2504 (tR= 15.9 min).

[0198] GC-MS: M = 275 (C16H21 NO3).

[0199] 1H NMR [ppm] = 6.81 (1 H, d, J = 8.42 Hz), 6.72 (1 H, dd, J = 8.47, 2.45 Hz), 6.69 (1 H, d, J = 2.40 Hz), 6.20 (1 H, s), 5.42 (1 H, s), 3.87 (3H, s), 3.84 (3H, s), 2.32 (2H, s), 2.21 (2H, s), 1.11 (6H, s).

[0200] 13C NMR [ppm] = 197.6, 161.2, 149.4, 147.3, 131.0, 117.1 , 111.5, 108.9, 98.3, 56.1 , 56.0, 50.4, 43.5, 32.9, 28.4.

[0201] Example 2: Synthesis of 2-bromo-3-(3,4-dimethoxyanilino)-5,5-dimethyl-cyclohex-2-en- 1 -one

[0202] The amide (200 g, 0.73 mol, 1 equiv) was added to ethanol (1300 g) under stirring and the resulting suspension was cooled to 15 °C. / V-bromosuccinimide (135 g, 0.76 mol, 1.05 equiv) was added in small portions to keep the internal reaction temperature below 17 °C. After complete addition, stirring was continued at 15 °C. After 4 hours, the precipitated solid was filtered off and was dried at 50 °C overnight to yield the common intermediate (261 .5 g, 90%) as a colorless solid.

[0203] GC Ret. Index (DB-1 ): 2645 (tR= 16.7 min).

[0204] GC-MS: M = 353 (Ci6H2oBrN03).

[0205] 1H NMR [ppm] = 7.22 (1 H, s), 6.87 (1 H, d, J = 8.44 Hz), 6.72 (1 H, ddd, J = 8.42, 2.47, 0.76 Hz), 6.66 (d, 1 H, J = 2.44 Hz), 3.92 (3H, s), 3.90 (3H, s), 2.43 (2H, d, J = 0.80 Hz), 2.34 (2H, s), 1.04 (6H, s)

[0206] 13C NMR [ppm] = 188.1 , 158.2, 149.5, 148.4, 130.2, 119.0, 111.3, 110.4, 96.0, 56.2, 56.1 , 50.8, 41.4, 32.7, 28.0. Example 3: Synthesis of 2-bromo-3-(3,4-dimethoxyanilino)-5,5-dimethyl-cyclohex-2-en- 1-one

[0207] Dimedone (4.5 g, 32 mmol, 1 equiv) and 3,4-dimethoxyaniline (5.0 g, 0.32 mmol, 1 .0 equiv) were suspended in ethanol (25 g) and the resulting mixture was heated to 40 °C. Then, a solution of p-toluene sulfonic acid (60 mg, 3.0 mmol, 10 mol%) in ethanol (1 g) was added and the reaction was heated to 80 °C. After five hours, the reaction was cooled down to 15 °C and / V-bromosuccinimide (5.8 g, 0.32 mmol, 1.0 equiv) was added in small portions. The suspension was stirred at 15 °C. After four hours, the precipitated solid was filtered off and the solid residue was washed with cold ethanol (5 g) to yield the common intermediate (6.1 g, 37%) was a colorless solid. The obtained analytical data is in accordance with the one obtained before.

[0208] Example 4: Synthesis of 8-(3,4-dimethoxyanilino)-6,6-dimethyl-2,3,5,7-tetrahydro-1 ,4- benzothiazine-3-carboxylic acid

[0209] The common intermediate (1.5 g, 4.2 mmol, 1 equiv) and cystein (60 mg, 5.0 mmol, 1.2 equiv) were suspended in ethanol (20 g) and pyridine (80 mg, 10 mmol, 2.5 equiv) was added. The mixture was heated to 80 °C. After eight hours, the solid was filtered off and the solid residue was washed with ethanol (5 g). LC analysis confirmed the formation of 8-(3,4-dimethoxyanilino)-6,6-dimethyl-2,3,5,7-tetrahydro-1 ,4-benzothiazine- 3-carboxylic acid.

[0210] Example 5: Synthesis of ethyl 2-[(3-anilino-5,5-dimethyl-cyclohex-2-en-1 -ylidene)-A5- azanyl]acetate

[0211] To a solution of dimedone (20 g, 0.14 mol, 1 equiv) and methanesulfonic acid (1.4 g, 14 mmol, 10 mol%) in toluene (100 g) was added aniline (13.3 g, 0.14 mol, 1.0 equiv). The resulting yellow solution was heated to 70 °C. After four hours, LC-MS indicated full conversion.

[0212] Glycine ethyl ester (12.6 g) was added to the obtained solution and the resulting mixture was heated to 110 °C in a Dean Stark apparatus. After eight hours, the precipitated solid was isolated by filtration and was washed with toluene.

[0213] LC: tR = 5.81 min.

[0214] LC-MS: MW = 300 (C18H24N2O2).

[0215] The following compounds are prepared by the preparation method of examples 1 and 5.

Claims

Claims1 . A process for the preparation of substituted enamines of general formula (III),(HI), whereinR1 is selected from the group consisting of CH2, unsubstituted or substituted CH(alkyl), unsubstituted or substituted C(alky 1)2, unsubstituted or substituted CH(cycloalkyl), unsubstituted or substituted CH(aryl), unsubstituted or substituted CH(heterocycloalkyl), unsubstituted or substituted CH(heteroaryl), -CR7R8 , C=O, halogen, 0, S, SO, SO2, NH, unsubstituted or substituted N(alkyl), unsubstituted or substituted N(alkenyl), unsubstituted or substituted N(alkynyl), unsubstituted or substituted N(alkoxy), unsubstituted or substituted N(alkylthio), unsubstituted or substituted N(cycloalkyl), unsubstituted or substituted N(aryl), unsubstituted or substituted N(heterocycloalkyl), unsubstituted or substituted N(heteroaryl), and unsubstituted or substituted C-spirocycles;R4, R5 and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=0)-, -CH2- OH, -R-CH2-OH, -C(= 0)-0-W, -R-C(=0)-0-W, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, SO, SO2, -S(=0)20H, sulfonyl, NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstitutedor substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), and unsubstituted or substituted NH(heteroaryl), unsubstituted or substituted NR9R10, and unsubstituted or substituted C-spirocycles;R7 and R8 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, -CH2- OH, -R-CH2-OH, -C(= O)-O-W, -R-C(=O)-O-W, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl, SO, SO2, NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstituted or substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), unsubstituted or substituted NH(heteroaryl) and unsubstituted or substituted NR9R10 ;W is selected from the group consisting of H and unsubstituted or substituted alkyl; andR is unsubstituted or substituted alkyl or alkylene; andR9 und R10 which may be identical or different, are independently from each other selected from the group consisting of H, OH, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocylcoalkyl, and unsubstituted or substituted heteroaryl; comprising at least the step of(A) reacting at least one compound of general formula (I),optionally in the form of its salts, hydrates and / or solvates, wherein R4, R5 and R6 are defined as above in general formula (III); with at least one compound of general formula (II),wherein R1 is defined as above general formula (III); to obtain a compound of general formula (III),wherein R1 , R4, R5 and R6 are defined as above.

2. The process according to claim 1 , wherein R1 is selected from the group consisting of CH2, C(alkyl)2, CH(alkyl), 0, S, SO, SO2, NH and N(alkyl), preferably R1 is selected from the group consisting of CH2 and C(methyl)2.

3. The process according to claim 1 or 2, wherein R4, R5 and R6 which may be identical or different, are independently from each other selected from the groupconsisting of H, OH, alkyl, preferably methyl, ethyl, propyl, iso-propyl, butyl, isobutyl or tert-butyl, alkoxy, preferably O-methyl, O-ethyl, or O-butyl, -S(=O)2OH, and sulfonyl.

4. The process according to according to any one of claims 1 to 3, wherein step (A) is carried out in the presence of at least one acid which is selected from the group consisting of inorganic acids, and organic sulfonic acids, preferably the organic sulfonic acids are selected from the group consisting of methane sulfonic acid, trifluoromethane sulfonic acid, trichloromethane sulfonic acid and p-toluene sulfonic acid.

5. The process according to any one of claims 1 to 4, wherein step (A) is carried out in the presence of at least one protic polar solvent, preferably the at least one protic polar solvent is an alcohol selected from the group consisting of methanol, ethanol, and isopropanol.

6. The process according to any one of claims 1 to 5, wherein step (A) is carried out in the presence of at least one aromatic solvent, preferably the at least one aromatic solvent is selected from the group consisting of toluene, xylene, cymene and mono-chlorobenzene.

7. A process for the preparation of substituted enamines of general formula (IV),(IV), wherein R1 , R4, R5 and R6 are defined as above in general formula (III) and Y isCl, Br or l; comprising at least the step of(B1 ) reacting at least one compound of general formula (III),(Ill), wherein R1 , R4, R5 and R6 are defined as above in general formula (III); with at least one halogenating agent to obtain a compound of general formula (IV).

8. The process according to claim 7, wherein, in case Y is Cl in the compound of general formula (IV), the at least one halogenating agent is a chlorinating agent selected from N-chlorosuccinimide and dichloroisocyanuric acid; in case Y in the compound of general formula (IV) is Br, the at least one halogenating agent is a brominating agent selected from the group consisting of KBr, N- bromosuccinimide or Br2 and in case Y is I, the at least one halogenating agent is a iodinating agent selected from the group consisting of KI, N-iodosuccinimide and I2.

9. The process according to claim 7 or 8, wherein step (B1 ) is carried out in the presence of at least one protic polar solvent, preferably the at least one protic polar solvent is at least one alcohol selected from the group consisting of methanol, ethanol, and isopropanol.

10. The process according to any one of 1 to 9, wherein steps (A) and (B1 ) are carried out in a one-pot reaction and the at least one solvent is at least one protic polar solvent.

11. A compound of general formula (IVa),(IVa), whereinR1 is selected from the group consisting of CH2, unsubstituted or substituted CH(alkyl), and unsubstituted or substituted C(alkyl)2;R5 is selected from the group consisting of OH, ethyl, propyl, iso-propyl, butyl, isobutyl, tert-butyl, unsubstituted or substituted alkoxy, SO, SO2, -S(=O)2OH, and sulfonyl;R4, and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, halogen, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted alkanoyl / acyl R-C(=O)-, -CH2- OH, -R-CH2-OH, -C(=O)-O-W, -R-C(=O)-O-W, SO, SO2, -S(=O)2OH, and sulfonyl;W is selected from the group consisting of H and unsubstituted or substituted alkyl; R is unsubstituted or substituted alkyl or alkylene; andY is Cl, Br or I; with the proviso that compounds, wherein R1 is C(methyl)2, R5 is O-methyl, R4 is H and R6 is H, and Y is Cl, Br or I, are excluded.

12. The compound of general formula (IVa) according to claim 11 , wherein R1 is selected from the group consisting of CH2 and C(methyl)2;R5 is selected from the group consisting of OH, ethyl, propyl, iso-propyl, butyl, isobutyl, tert-butyl, O-methyl, O-ethyl, O-butyl, -S(=O)2OH, and sulfonyl:R4, and R6 which may be identical or different, are independently from each other selected from the group consisting of H, OH, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, O-methyl, O-ethyl, O-butyl, -S(=O)2OH, andsulfonyl; and n is 1 ; preferably the compound of general formula (IVa) is2-bromo-3-(3,4-dimethoxyanilino)-5,5-dimethyl-cyclohex-2-en-1-one13. A process for the preparation of substituted enamines of general formula (VI),(VI), whereinR1 , R4, R5, and R6, are defined as above in general formula (III);A is S; R2 is -C(=O)-O-W; and W is selected from the group consisting of H and unsubstituted or substituted alkyl; comprising at least the step of:(C1 ) reacting at least one compound of general formula (IV),(IV), as defined in any one of claims 7 to 12, with at least one compound of general formula (VII),(VII), optionally in the form of its salts, hydrates and / or solvates, wherein R2 is defined as above in general formula (VI), to obtain a compound of general formula (VI).

14. The process according to claim 13, wherein step (C1 ) is carried out in the presence of at least one protic polar solvent, preferably the at least one protic solvent is an alcohol selected from the group consisting of methanol, ethanol, and isopropanol.

15. The process according to claim 13 or 14, wherein step (C1 ) is carried out in the presence of at least one organic base which is selected from the group consisting of N(R26)s, N-methyl piperidine, N-methyl pyrrolidine, N-methyl morpholine, piperidine, dimethyl amino pyridine, pyridine, and tetra-Ci-Ce-alkyl ammonium hydroxide, wherein R26is, identical or different, hydrogen, Ci-Ce-alkyl, Cs-Ci4-aryl, or Cs-Ce-cycloalkyl.

16. A process for the preparation of substituted enamines of general formula (X),(X),wherein R1 , R4, R5 and R6 are defined as above in general formula (III) and Z is selected from the group consisting of O-R11 or amide’;R11 is selected from the group consisting of H, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted alkoxy, unsubstituted or substituted alkylthio, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted heteroaryl; amide’ is selected from the group consisting of NH2, unsubstituted or substituted NH(alkyl), unsubstituted or substituted NH(alkenyl), unsubstituted or substituted NH(alkynyl), unsubstituted or substituted NH(alkoxy), unsubstituted or substituted NH(alkylthio), unsubstituted or substituted NH(cycloalkyl), unsubstituted or substituted NH(aryl), unsubstituted or substituted NH(heterocycloalkyl), unsubstituted or substituted NH(heteroaryl), and unsubstituted or substituted NR9’R10’, unsubstituted or substituted -N(O-alkyl)(alkyl) (Weinreb amide), - N(OH)(H) (hydroxamate), and unsubstituted or substituted -N(OH)(alkyl) (alkylated hydroxamate); comprising at least the step of(C2) reacting at least one compound of general formula (III),(HI), wherein R1 , R4, R5 and R6 are defined as above in general formula (III); with at least one compound of general formula (XI),(XI), optionally in the form of its salts, hydrates and / or solvates, wherein Z is defined as above in general formula (X), to obtain a compound of general formula (X).

17. The process according to claim 16, wherein- R11 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl,butyl, isobutyl, tert-butyl, (2-ethylhexyl) and phenyl; or - amide’ is selected from the group consisting of NH2, NH(alkyl) and N(alkyl)2, - N(O-alkyl)(alkyl) (Weinreb amide) and -N(OH)(H) (hydroxamate.

18. The process according to any one of claims 1 to 17, wherein steps (A) and (C2) are carried out in a one-pot reaction and the at least one solvent is at least one aromatic solvent.

19. A compound of general formula (X) as defined in claim 16 which is selected from the group consisting of 2-[(5,5-dimethyl-3-phenylimino-cyclohexen-1 - yl)amino]acetic acid, 2-[(3-phenyliminocyclohexen-1 -yl)amino]acetic acid, 2,5,5- trimethyl-3-(phenylimino)cyclohex-1 -en-1 -yl-g lycine, 2-[(2-methyl-3-phenylimino- cyclohexen-1 -yl)amino]acetic acid, 3-((3,4-dimethoxyphenyl)imino)-5,5- dimethylcyclohex-1 -en-1 -yl-g lycine, 3-((3,4-dimethoxyphenyl)imino)cyclohex-1 - en-1 -yl-g lycine, 3-((3,4-dimethoxyphenyl)imino)-2,5,5-trimethylcyclohex-1 -en-1 - yl-glycine, 2-[(3-(3,4-dimethoxyphenyl)imino-2-methyl-cyclohexen-1- yl)amino]acetic acid, 2-[(5,5-dimethyl-3-(4-sulfophenyl)imino-cyclohexen-1 - yl)amino]acetic acid, 2-[(3-(4-sulfophenyl)iminocyclohexen-1 -yl)amino]acetic acid, 2,5,5-trimethyl-3-((4-sulfophenyl)imino)cyclohex-1 -en-1 -yl-glycine, 2-methyl-3-((4-sulfophenyl)imino)cyclohex-1 -en-1 -yl-g lycine, 2-[(5,5-dimethyl-3- phenylimino-cyclohexen-1 -yl)amino]acetamide, 2-[(3-phenyliminocyclohexen-1 - yl)amino]acetamide, 2-((2,5,5-trimethyl-3-(phenylimino)cyclohex-1-en-1- yl)amino)acetamide, 2-((2-methyl-3-(phenylimino)cyclohex-1 -en-1 - yl)amino)acetamide, 2-((3-((3,4-dimethoxyphenyl)imino)-5,5-dimethylcyclohex-1- en-1 -yl)amino)acetamide, 2-[(3-(3,4-dimethoxyphenyl)iminocyclohexen-1 - yl)amino]acetamide, 2-((3-((3,4-dimethoxyphenyl)imino)-2,5,5-trimethylcyclohex- 1 -en-1 -yl)amino)acetamide, and 2-((3-((3,4-dimethoxyphenyl)imino)-2- methylcyclohex-1 -en-1 -yl)amino)acetamide.

20. The compound according to claim 19 which is obtained by the process according to any one of claims 1 to 16.

Images