ES2369813T3 - DERIVATIVES OF AMINOTRIAZOL AS AGONISTS OF AXL. - Google Patents

Abstract

A compound of the formula (I), in which A represents a phenyl- or a heterocyclyl group, in which the two substituents are in a 1.3 arrangement; or A represents propan-1,3-diyl; E represents * - C1-C4 alkyl -O-, -CH = CH- or in which the asterisks indicate the bond that is linked to R1; Q represents O or S; R3 represents hydrogen, C1-C4 alkyl, cyclopropyl, C1-C4 alkoxy-C1-C4 alkyl, benzyl or -CH2CH2C (O) OtBu; R1 represents a pyridyl group or an aryl group, wherein said group is unsubstituted, mono-, di- or tri-substituted, in which the substituents are independently selected from the group consisting of halogen, C1-C4 alkyl, alkoxy C1-C4, C1-C4 fluoralkyl, C1-C4 fluoralkoxy, di- [C1-C3 alkyl] -amino and C1-C4 alkoxy C1-C2 alkyl; and R2 represents -CO-C1-C3 alkyl, -CF2-C1-C3 alkyl, or -SO2 C1-C3 alkyl; or a salt of said compound.

Description

Aminotriazole derivatives as AXL agonists

The present invention relates to new aminotriazole derivatives of formula (I) and their use as pharmaceuticals. The invention also relates to related aspects that include processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of formula (I), and especially their use as agonists of the ALX receptor.

ALXR (aka Lipoxin Receptor A4, FPRL1; described in WO2003 / 082314 as the nucleotide sequence SEQ ID NO: 1) is a member of the receptor family coupled to the G protein. It was found that ALXR acted as an intermediate in the calcium mobilization in response to a high concentration of the formyl-methionine-leucyl-phenyl alanine peptide. In addition, it was found that a lipid metabolite, lipoxin A4 (LXA4), and its analogs, adhered to ALXR with high affinity and increased production of arachidonic acid and activation of G protein in cells transfected with ALXR (Chiang et al. , Pharmacol. Rev., 2006, 58, 463-487). The effects of LXA4 have been evaluated in a variety of animal disease models; and it was shown that LXA4 had potent anti-inflammatory and pro-resolutive activities. The disease models in which LXA4, or derivatives, or stable analogues, demonstrate activity in vivo, are for example dermal inflammation, dorsal sac fundus, ischemia / reperfusion lesions, peritonitis, colitis, proliferative mesangio nephritis, pleurisy, asthma, cystic fibrosis, septicemia, corneal lesions, angiogenesis, periodontitis, carrageenan-induced hyperalgesia, and graft-vs-host disease (GvHD) (Serhan and Chiang, Br. J. Pharmacol., 2007, 1–16). ALXR was also identified as a functional receptor of a varied number of peptides, including a prion protein fragment, a peptide derived from the gp120 strain of Human Immunodeficiency Virus (HIV) –1LAI, and amyloid – beta 1–42 (Ab42 ) (for a review, see Le et al., Protein Pept Lett., 2007,14, 846–853), and it has been suggested that it participates in the pathogenesis of Alzheimer's Disease (AD) in several crucial pathways (Yazawa et al., FASEB J., 2001, 15, 2454-2462). ALXR activation in macrophages and microgliocytes initiates a signaling cascade mediated by G protein that increases directional cell migration; Phagocytosis and the release of the mediator. These events may count for the recruitment of mononuclear cells in the vicinity of senile plaques in areas of the brain ill with AD, where Ab42 is hyper-produced and accumulated. Although the accumulation of leukocytes at the sites of tissue lesions can be considered an innate host response aimed at the clearance of harmful agents, activated mononuclear phagocytes also release a variety of substances, such as activated mononuclear phagocytes, such as superoxide anions that can be toxic to neurons. Therefore, ALXR can mediate the pro-inflammatory responses produced by Ab42 in brains with AD and exacerbate the progression of the disease. It was also reported that humanin (HN), a peptide with neuroprotective abilities, shares human ALXR with Ab42 on phagocytes and neuronal cell lines and it has been suggested that the neuroprotective activity of HN can be attributed to its competitive occupation with ALXR (Ying et al., J. Immunol., 2004, 172, 7078-7085).

Pyrazolone and other heterocyclic derivatives that have agonist activity of ALXR agonist are described in the Bioorg documents. Med. Chem. Lett. 2006, 16, 3713-3718 and WO 2005/047899.

The biological properties of ALXR agonists include, but are not limited to, migration / activation of monocyte / macrophage / microgliocytes; Neutrophil migration / activation, lymphocyte activation regulation, proliferation regulation and differentiation inflammation regulation, cytokine production and / or release regulation, production regulation and / or pro-inflammatory mediator release, and / o production release of the pro-inflammatory mediator, regulation of the immune reaction.

The present invention provides aminotriazole derivatives, which are non-peptide agonists of the human ALX receptor. The compounds are useful for the prevention or treatment of diseases that respond to modulation of the ALX receptor, such as inflammatory diseases, airway obstruction, allergic conditions, HIV-mediated retroviral infections, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases, and amyloid-mediated disorders (especially Alzheimer's disease); They are also useful in the prevention or treatment of autoimmune diseases and for the modulation of immune responses (especially those caused by vaccination).

Several embodiments of the invention are presented below.

1) The present invention relates to aminotriazole derivatives of formula (I),

H

(I)

where

A represents a phenyl- or heterocyclyl- group, in which the two substituents are in an arrangement of 1.3–; or A represents propan-1,3-diyl;

E represents * -C1-C4-O-alkyl, -CH = CH- or;

in which the asterisks indicate the bond that is attached to R1;

Q represents O or S;

R3 represents hydrogen, C1-C4 alkyl, cyclopropyl, C1-C4 alkoxy-C1-C2 alkyl, benzyl or -CH2CH2C (O) OtBu;

R1 represents a pyridyl group, or an aryl group, said group is unsubstituted, mono-, di- or tri-substituted, in which the substituents are independently selected from the group consisting of halogen, C1-C4 alkyl, C1 alkoxy -C4, C1-C4 fluoralkyl, C1-C4 fluoralkoxy, di- [C1-C3 alkyl] -amino and C1-C4 alkoxy-C1-C2 alkyl; Y

R2 represents -CO-C1-C3 alkyl, -CF2-C1-C3 alkyl, or -SO2-C1-C3 alkyl.

The compounds of formula (I) according to embodiment 1) may contain one or more stereogenic centers

10 or asymmetric, such as one or more asymmetric carbon atoms. Unless otherwise indicated, substituents on a double bond may be present in the (Z) - or (E) - configuration. The compounds of formula (I) may therefore be present as mixtures of stereoisomers or preferably as pure stereoisomers. Mixtures of stereoisomers may be separated in a manner known to one skilled in the art.

In the case where E represents –CH = CH– the double bond may be present in the configuration (Z) - or (E) -, preferably it is present in the configuration (E) -.

The following paragraphs provide definitions of various chemical portions for the compounds according to the invention and will be applied uniformly throughout the specification and claims unless another expressly established definition provides a more or less broad definition.

The term "alkyl" used alone or in combination, refers to a straight or branched chain alkyl group containing one to four carbon atoms. The term "(Cx-Cy) alkyl" (x and y are each an integer), refers to an alkyl group as defined above that contains atoms of x a and carbon atoms. For example, a C1-C4 alkyl group contains from one to four carbon atoms. Representative examples of alkyl groups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl. They prefer

C1-C3 alkyl groups, such as methyl, ethyl, n-propyl and iso-propyl. More preferred are C1-C3 alkyl groups such as methyl and ethyl. More preferred is methyl.

An example of a (C1-C3) alkyl group such as that used in R2 representing alkyl -CO- (C1-C3), -CF2- (C1-C3) alkyl or -SO2-(C1-C3) alkyl is methyl. In a bridged C1-C4 alkyl group as used in E representing * -C1-C4 alkyl -O-, the atom of

Oxygen and the R1 moiety are preferably attached to the same carbon atom of the bridged (C1-C4) alkyl group.

The term "alkoxy", used alone or in combination, refers to an alkyl-O- group where the alkyl group is as defined above. The term "alkoxy (Cx-Cy)" (x and y are each an integer) refers to an alkoxy group as defined above containing x a and carbon atoms. For example a (C1-C4) alkoxy group containing from one to four carbon atoms. Representative examples of alkoxy groups include

Methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy and tert-butoxy. Preferred are ethoxy and methoxy. The most preferred is methoxy. The term "fluoralkyl" refers to an alkyl group as defined above that contains one to four (preferably one to three) carbon atoms, in which one or more (and possibly all) hydrogen atoms has been replaced with fluorine. The term "fluoralkyl (Cx – Cy)" (x and y are each an integer) is

40 refers to a fluoralkyl group as defined above containing x a and carbon atoms. For example a fluoralkyl (C1-C3) group contains from one to three carbon atoms in which one to seven hydrogen atoms have been replaced with fluorine. Representative examples of fluoralkyl groups include trifluoromethyl and 2,2,2-trifluoroethyl. Fluoralkyl (C1), such as trifluoromethyl and difluoromethyl, is preferred. The most preferred is trifluoromethyl.

The term "fluoralkoxy" refers to an alkoxy group as defined above that contains one to four

45 (preferably one to three) carbon atoms in which one or more (and possibly all) hydrogen atoms have been replaced with fluorine. The term "fluoralkoxy (Cx-Cy)" (x and y are each an integer) refers to a fluoralkoxy group as defined above containing x a and carbon atoms. For example a fluoralkoxy group (C1-C3) contains from one to three carbon atoms in which one to seven hydrogen atoms have been replaced with fluorine. Representative examples of fluoralkoxy groups include

50 trifluoromethoxy, difluoromethoxy and 2,2,2-trifluoroethoxy. Slel prefer C1 fluoroalkoxy groups such as trifluoromethoxy and difluoromethoxy. The most preferred is trifluoromethoxy.

The term "hydroxy-C1-C2 alkyl" refers to an alkyl group as defined above that contains one or two carbon atoms in which a hydrogen atom has been replaced with hydroxy. Examples of hydroxy-C1-C2 alkyl groups are hydroxy methyl and hydroxy ethyl. Preferred are hydroxy-methyl and 2-hydroxy-ethyl.

The term "C1-C4 alkoxy-C1-C2 alkyl" refers to an alkyl group as defined above that contains one or two carbon atoms in which an alkyl group is as defined above and contains one or two carbon atoms in which a hydrogen atom has been replaced by C1-C4 alkoxy as defined above. Representative examples of C1-C4 alkoxy-C1-C2 alkyl groups include

methoxy-methyl, methoxy-ethyl (especially 2-methoxy-ethyl), ethoxy-methyl, ethoxy-ethyl (especially 2-ethoxy-ethyl), isopropoxy-methyl and isopropoxy-ethyl (especially 2-isopropoxy-ethyl); and preferably methoxy-methyl, methoxy-ethyl (especially 2-methoxy-ethyl), ethoxy-methyl and ethoxy-ethyl (especially 2-ethoxy-ethyl).

Preferred examples of C1-C4-alkoxy-C1-C2 alkyl groups as used in R1 are methoxy-methyl, methoxy-ethyl (especially 2-methoxy-ethyl), ethoxy-methyl, ethoxy-ethyl (especially 2– ethoxy-ethyl), isopropoxy-methyl and isopropoxy-ethyl (especially 2-isopropoxy-ethyl). Most preferred are methoxy-methyl and methoxy-ethyl (especially 2-methoxy-ethyl).

Preferred examples of C1-C4-alkoxy-C1-C2 alkyl groups as used in R3 are methoxy-methyl and methoxy-ethyl (especially 2-methoxy-ethyl). Most preferred is methoxy methyl.

The term "di- [C1-C3 alkylamino]" refers to an amino group that is substituted by two C1-C3 alkyl groups as defined above, where the two C1-C3 alkyl groups may be the same or different. Representative examples of di- [C1-C3 alkylamino] groups include, but are not limited to dimethylamino, methyl-ethyl-amino and diethylamino. Dimethylamino is preferred.

The term "halogen" means fluorine, chlorine or bromine or iodine, preferably fluorine, chlorine or bromine and more preferably fluorine or chlorine.

The term "aryl", alone or in any combination means phenyl (preferred) or naphthyl. The aryl group is unsubstituted, mono-, di-, or tri-substituted (preferably unsubstituted, mono- or di-substituted and more preferably unsubstituted, or mono-substituted), where the substituents are independently selected from the group consisting in halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoralkyl, C1-C4 fluoralkoxy, di– [C1-C3 alkylamino] and C1-C4 alkoxy-C1-C2 alkyl and preferably halogen, C1-C4 alkyl , C1-C4 alkoxy, C1-C4 fluoralkyl and C1-C4 fluoralkoxy. Examples are phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-chloro-4-fluorphenyl, 3-fluorphenyl, 4-fluorphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3,5-dimethylphenyl , 3-methoxyphenyl, 4-methoxyphenyl, 3-methoxy-4-methylphenyl, 3-methoxymethyl-phenyl, 3-methoxyethyl-phenyl, 3-dimethylamino-phenyl, 2-trifluoromethyl-phenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, and 3-trifluoromethoxyphenyl. Additional examples are 3-isopropoxymethyl-phenyl and 3- (2-isopropoxy-ethyl) -phenyl. Preferred examples are phenyl, 3-methoxyphenyl and 4-trifluoromethylphenyl.

The term "heterocyclyl", alone or in combination, means a 5- or 6-membered monocyclic aromatic ring containing 1, 2 or 3 heteroatoms independently selected from oxygen, nitrogen and sulfur. Examples of such heterocyclyl groups are furanyl, oxazolyl, isoxazolyl, oxadiazolyl, thienyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrimidyl, pyridazinyl, and pyrazinyl. Preferred examples are furanyl (especially furan-2,5-diyl), thienyl (especially thiophene-2,4-diyl and thiophene-2,5-diyl), thiazolyl (especially thiazol-2,4-diyl), and pyridyl ( especially pyridin-2,4-diyl and pyridin-2,6-diyl). An additional preferred example is oxazolyl (especially oxazol-2,4-diyl and oxazol-2,5-diyl). The most preferred examples are furan-2,5-diyl, oxazol-2,4-diyl, oxazol-2,5-diyl, thiophene-2,5-diyl and thiazol-2,4-diyl. The most preferred examples are furan-2,5-diyl and thiophene-2,5-diyl and especially furan-2,5-diyl.

The term "arrangement 1.3" as used in the detailed description of "A" means that the two atoms of the phenyl or heterocyclyl group that are attached to the triazole-methyl portion and the residue R2 respectively are separated from each other. by an atom; For example, if "A" represents phenyl, the arrangement of the substituents is as shown in the following figure:

H

In this patent application, the dotted line shows the junction point of the plotted radical. For example, the radical plotted below

it is the 2-methyl-oxazol-4,5-diyl group.

2) A further embodiment of the invention relates to aminotriazole derivatives according to embodiment 1), wherein A represents a phenyl- or heterocyclyl group, in which the two substituents are in the arrangement of 1.3; or A

represents propan-1,3-diyl; E represents * –CH2 – O–, –CH = CH– or;

in which the asterisks indicate the bond that is attached to R1; Q represents O or S; R3 represents hydrogen, C1-C4 alkyl, cyclopropyl or C1-C4 alkoxy-C1-C2 alkyl;

R1 represents an aryl group, said group is unsubstituted, mono-, di- or tri-substituted, in which the substituents are independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-fluoroalkyl -C4, C1-C4 fluoralkoxy, di- [C1-C3 alkylamino] and C1-C4 alkoxy C1-C2 alkyl; Y

R2 represents -CO-C1-C3 alkyl, -CF2-C1-C3 alkyl, or -SO2-C1-C3 alkyl. 3) A further embodiment of the invention relates to aminotriazole derivatives according to embodiment 1), wherein

A represents a phenyl- or heterocyclyl group, in which the two substituents are in a 1.3 arrangement; or A represents propan-1,3-diyl; E represents * –alkyl (C1 – C4) –O–, –CH = CH– or

;

Where the asterisks indicate the bond that is attached to R1;

Q represents O or S;

R3 represents hydrogen, C1-C4 alkyl, or cyclopropyl;

R1 represents an aryl group, said group is unsubstituted, mono-, di- or tri-substituted, in which the substituents

are independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluororalkoxy, di– [alkylamino (C1-C3)] and C1-C4 alkoxy-C1 alkyl –C2); Y

R2 represents -CO-C1-C3 alkyl, -CF2-C1-C3 alkyl, or -SO2-C1-C3 alkyl. 4) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) or 2), in which

A represents phenyl-1,3-diyl, furan-2,5-diyl, oxazol-2,4-diyl, oxazol-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl, Thiazol-2,4-diyl, thiazol-2,5-diyl, pyridin-2,4-diyl, pyridin-2,6-diyl or propan-1,3-diyl;

E represents * –CH2 – O–, –CH = CH– or

;

in which the asterisks indicate the bond that is attached to R1; R3 represents hydrogen, C1-C4 alkyl, cyclopropyl or C1-C4 alkoxy-C1-C2 alkyl; R1 represents an aryl group, said group is unsubstituted, mono-, di- or tri-substituted, where the substituents

are independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoralkyl, C1-C4 fluoralkoxy, di- [C1-C3 alkylamino] and C1-C4 alkoxy-C1-C2 alkyl; Y R2 represents -CO-C1-C3 alkyl, -CF2-C1-C3 alkyl, or -SO2-C1-C3 alkyl. 5) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

Embodiments 1) to 4), where at least one, preferably all of the following features are present:

A represents phenyl-1,3-diyl, furan-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl, thiazol-2,4-diyl, pyridine-2,4-diyl, pyridin-2,6-diyl or propan-1,3-diyl; E represents * –CH2 – O–, –CH = CH– or

;

where the asterisks indicate the bond that is attached to R1; R3 represents hydrogen, C1-C4 alkyl or cyclopropyl; R1 represents an aryl group, said group is unsubstituted, mono-, di- or tri-substituted, where the substituents

5 are independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoralkyl, C1-C4 fluoralkoxy, di– [C1-C3 alkylamino] and C1-C4 alkoxy-C1-C2 alkyl; Y

R2 represents -CO-C1-C3 alkyl, -CF2-C1-C3 alkyl, or -SO2-C1-C3 alkyl. 6) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 4), in which

10 A represents furan-2,5-diyl, oxazol-2,4-diyl, oxazol-2,5-diyl, thiophene-2,5-diyl or thiazol-2,4-diyl; E represents * –CH2 – O–, –CH = CH– or

;

where the asterisks indicate the bond that is attached to R1; R3 represents hydrogen, methyl, ethyl or cyclopropyl; R1 represents a phenyl group, wherein said group is unsubstituted, mono- or di-substituted, where the substituents

are independently selected from the group consisting of halogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, and dimethylamino; Y R2 represents –CO – CH3. 7) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

20 embodiments 1) to 6), where at least one, preferably all of the following characteristics are present: A represents furan-2,5-diyl or thiophene-2,5-diyl (especially furan-2,5-diyl); E represents

;

in which the asterisks indicate the bond that is attached to R1; R3 represents hydrogen or methyl; R1 represents a phenyl group, said group is unsubstituted, mono- or di-substituted, where the substituents are

independently selected from the group consisting of halogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, and dimethylamino; and R2 represents –CO – CH3.

8 8) A further embodiment of the invention relates to compounds of formula (I) which are also compounds of formula (IP) E represents * -C1-C4-O-alkyl, -CH = CH- or

;

in which the asterisks indicate the bond that is attached to R1; R3 represents hydrogen or (C1-C4) alkyl; R1

represents aryl, which is unsubstituted, mono-, di- or tri-substituted, where the substituents are

independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-fluoroalkyl

C4 and C1-C4 fluoralkoxy; Y

R2 represents -CO-C1-C3 alkyl.

9) A further embodiment of the invention relates to aminotriazole derivatives according to any of the embodiments 1) to 3), in which A represents heterocyclyl, where the two substituents are in a 1.3 arrangement. 10) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 4), in which A represents phenyl-1,3-diyl, furan-2,5-diyl, oxazol-2,4-diyl, oxazol-2,5-diyl (especially with R2 attached in the

position 2), thiophene-2,4-diyl, thiophene-2,5-diyl, thiazol-2,4-diyl (especially with R2 attached in position 4), thiazole– 2,5-diyl, pyridin-2,4-diyl, pyridin-2,6-diyl or propan-1,3-diyl. 11) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 5) or 10), in which

A represents phenyl-1,3-diyl, furan-2,5-diyl, thiophene-2,4-diyl (with R2 attached in position 2), thiophene-2,5-diyl, thiazole- 2,4-diyl (with R2 attached in position 4), pyridin-2,4-diyl, pyridin-2,6-diyl or propan-1,3-diyl. 12) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 4), 6), 9) or 10), in which A represents furan-2,5-diyl, oxazol-2,4-diyl with R2 attached in position 2, oxazol-2,4-diyl with R2 attached in the

position 4, oxazol-2,5-diyl with R2 attached in position 2, thiophene-2,5-diyl or thiazole-2,4-diyl with R2 attached in the position 4. 13) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 7) or 9) to 12), in which A represents furan-2,5-diyl or thiophene-2,5-diyl. 14) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 6) or 9) to 12), in which A represents thiazol-2,4-diyl (with R2 attached at position 4). 15) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 7) or 9) to 13), in which A represents thiophene-2,5-diyl. 16) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 7) or 9) to 13), in which A represents furan-2,5-diyl. 17) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 4), 6), 9), 10) or 12), in which A represents oxazol-2,4-diyl with R2 attached in position 2 or oxazol-2,4-diyl with R2 attached in position 4. 18) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 4), 6), 9), 10) or 12), in which A represents oxazol-2,4-diyl with R2 attached in position 2. 19) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 4), 6), 9), 10) or 12), in which A represents oxazol-2,4-diyl with R2 attached in position 4.

20) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 4), 6), 9) or 10), wherein A represents oxazol-2,5-diyl with R2 attached in position 2 or oxazol-2,5-diyl with R2 attached in position 5 .. 21) A further embodiment of the invention relates to aminotriazole derivatives according to any of the 5 embodiments 1) to 4), 6), 9), 10) or 12), in which

A represents oxazol-2,5-diyl with R2 attached in position 2. 22) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 5), 10) or 11), in the that

A represents phenyl-1,3-diyl.

23) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 5), 10) or 11), wherein A represents propan-1,3-diyl. 24) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 6) or 8) to 23), in which

E represents * -C1-C4-O-alkyl (preferably * -CH2-O-) or -CH = CH-, where the asterisks indicate the bond that is attached to R1; 25) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 6) or 8) to 24), in which E represents * -C1-C4-O-alkyl (preferably * -CH2-O-), 20 where the asterisks indicate the bond that is attached to R1;

26) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 6) or 8) to 24), in which E represents -CH = CH-. 27) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

25 embodiments 1) to 23), where E represents

,

where the asterisks indicate the bond that is attached to R1; 28) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1), 2), 4), 9) to 23) or 27), wherein R3 represents hydrogen, C1-C4 alkyl , cyclopropyl, methoxy-methyl or 2-methoxy-ethyl.

29) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 23) or 27), wherein R3 represents hydrogen or methyl. 30) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

Embodiments 1) to 3) or 9) to 23), in which Q represents O. 31) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 5) or 9) to 30), in which

R1

represents phenyl, which is unsubstituted, mono- or di-substituted, where the substituents are independently selected from the group consisting of halogen, C1-C4 alkyl (especially methyl), (C1-C4) alkoxy (especially methoxy), trifluoromethyl , trifluoromethoxy, and dimethylamino.

32) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 31), wherein R 1 represents phenyl, which is unsubstituted or mono-substituted where the substituent is selected from the group consisting of halogen , C1-C4 alkoxy (especially methoxy) and trifluoromethyl.

33) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) or 9) to 30), in which

R1

represents pyridyl, which is unsubstituted, mono-, di- or tri-substituted, where the substituents are independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoralkyl, C1-C4 fluoralkoxy , di– [C1-C3 alkylamino] and C1-C4 alkoxy-C1-C2 alkyl.

34) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) or 9) to 30), in which

R1 represents pyridyl, which is mono-substituted with C1-C4 fluoralkyl (especially trifluoromethyl). 35) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 5) or 9) to 34), wherein R2 represents -CO-C1-C3 alkyl (especially -CO-CH3) or –CF2 – C1 – C3 alkyl (especially –CF2 – CH3).

36) A further embodiment of the invention relates to aminotriazole derivatives according to any of the

embodiments 1) to 5) or 9) to 35), where R2 represents -CF2-C1-C3 alkyl (especially -CF2-CH3). 37) A further embodiment of the invention relates to aminotriazole derivatives according to any of embodiments 1) to 35), wherein R2 represents -CO-C1-C3 alkyl (especially -CO-CH3).

38) Preferred compounds of formula (I) as defined in embodiment 1) are selected from the group consisting of:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-phenyl-oxazol-4-carboxylic acid, N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide (preferably (E) –N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide);

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-phenyl) –2-methyl-oxazol – 4– carboxylic ;

2-Chloro-benzyl ester of [2– (5-Acetylfuran-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; where the double bond of acrylamide derivatives cited in the above list may be in the configuration (E) - or (Z) - (preferably in the configuration (E) -).

39) Additional preferred compounds of formula (I) as defined in embodiment 1, are selected from the group consisting of:

[2– (5 – oxo-hexyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-phenyl-oxazol-4-carboxylic acid; N– [2– (5 – acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-chloro-phenyl) -acrylamide (preferably (E) –N– [2– (5– acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-chloro-phenyl) -acrylamide);

N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-trifluoromethyl-phenyl) -acrylamide (preferably (E) –N– [2-

(5 – Acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-trifluoromethyl-phenyl) -acrylamide); N– [2– (5 – acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) –acrylamide (preferably (E) –N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) -acrylamide);

N– [2– (5 – acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3 – o-tolyl-acrylamide (preferably (E) –N– [2– ( 5-

acetylfuran-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -3-o-tolyl-acrylamide); N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-chloro-4-fluor-phenyl) -acrylamide (preferably (E ) –N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-chloro-4-fluor-phenyl) -acrylamide);

N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3-m-tolyl-acrylamide (preferably (E) –N– [2– ( 5-

acetylfuran-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -3-m-tolyl-acrylamide); N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3-p-tolyl-acrylamide (preferably (E) –N– [2– ( 5– Acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3-p-tolyl-acrylamide);

N– [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-methoxy-phenyl) -acrylamide (preferably (E) –N– [2– (5–

Acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-methoxy-phenyl) -acrylamide); [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3,5-dimethyl-phenyl) –2-methyl-oxazole– 4– carboxylic;

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-trifluoromethyl-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2-methyl-oxazole – 4– carboxylic; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (4-chloro-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid;

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazole-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2-methyl-oxazole – 4– carboxylic; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-4-methyl-phenyl) –oxazol – 4–

carboxylic; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (4-fluorophenyl) -oxazole-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-m-tolyl-oxazol-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-methoxy-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5– (3-trifluoromethyl-phenyl) -oxazole-4–

carboxylic;

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole – 4– carboxylic; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-o-tolyl-oxazol-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-ethyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetylfuran-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-cyclopropyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-fluorophenyl) -oxazole-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-chloro-phenyl) -oxazole-4-carboxylic acid; [2– (5-Acetylthiophe-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (3-Acetylbenzyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (3-Acetylbenzyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; [2– (5,5-difluor-hexyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-methanesulfonyl-furan-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-dimethylamino-phenyl) -oxazole-4-carboxylic acid; [2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (4-acetylthiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; 2-Chloro-benzyl ester of [2– (4-acetylpyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; [2– (5 – acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– [3– (2-methoxy-ethyl) –phenyl] –oxazole– 4-carboxylic; [2– (6-Acetylpyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-Acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-methoxymethyl-phenyl) -oxazole-4-carboxylic acid; [2– (2-Acetyl thiazol-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (4-Acetylpyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (2-Acetylpyridin-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (2-Acetylpyridin-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; [2– (5-acetylthiophe-3-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; Y [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid: where the double bond of acrylamide derivatives mentioned in the above list may be in the configuration (E) - or (Z) -

(preferably in configuration (E) -).

40) Additional preferred compounds of formula (I) as defined in embodiment 1) are selected from the group consisting of: [2– (3-Acetylisoxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-isopropoxymethyl-phenyl) –oxazol – 4–

carboxylic;

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– [3– (2-Iiopropoxy-ethyl) –phenyl] –oxazole– 4- carboxylic; [2– (5-Acetylthiophe-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid;

[2– (5-acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2 – methyl-oxazol – 4– carboxylic; [2– (5-Acetylthiophe-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-m-tolyl-oxazol-4-carboxylic acid; [2– (5-Acetylthiophe-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-phenyl-oxazol-4-carboxylic acid;

[2– (5-acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole – 4– carboxylic; [2– (5-acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-fluorophenyl) -oxazole-4-carboxylic acid; [2– (5-acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-dimethylamino-phenyl) -oxazole-4-carboxylic acid; [2– (5-Acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-chloro-phenyl) -oxazole-4-carboxylic acid;

[2– (5-acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole – 4– carboxylic; [2– (5-Acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (4-fluorophenyl) -oxazole-4-carboxylic acid; [2– (5-acetylthiophe-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazole-4-carboxylic acid; [2– (5-Acetylthiophe-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-methoxy-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-fluorophenyl) -thiazole-4-carboxylic acid;

[2– (2-Acetyl thiazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (2-acetylthiazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; N– [2– (2-acetylthiazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide; [2– (2-Acetyloxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (5-acetylthiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; [2– (4-Acetylthiophe-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; N– [2– (5-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide; [2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid; [2– (4-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2 – methyl-oxazol – 4– carboxylic;

[2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-phenyl-oxazol-4-carboxylic acid; [2– (4-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole-4– carboxylic; [2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-fluorophenyl) -oxazole-4-carboxylic acid; [2– (4-Acetylthiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-dimethylamino-phenyl) -oxazole-4-carboxylic acid; [2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-chloro-phenyl) -oxazole-4-carboxylic acid; [2– (4-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole-4–

carboxylic; [2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (4-fluorophenyl) -oxazole-4-carboxylic acid; [2– (4-Acetyl thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazole-4-carboxylic acid; [2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-methoxy-phenyl) -oxazole-4-carboxylic acid; N– [2– (4-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide; N– [2– (4-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) -acrylamide; [2– (4-acetyl thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-phenyl) –2-methyl-oxazol – 4–

carboxylic;

[2– (4-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2-methyl-oxazole – 4– carboxylic;

[2– (4-Acetyl thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid;

[2– (4-Acetyloxazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid;

[2– (5-Acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methoxymethyl-5-phenyl-oxazol-4-carboxylic acid;

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 2– (2-methoxy-ethyl) –5-phenyl-oxazol – 4– carboxylic;

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-butyl-5-phenyl-oxazol-4-carboxylic acid;

[2– (5-Acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-isopropyl-5-phenyl-oxazol-4-carboxylic acid;

N– [2– (4-acetylthiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-trifluoromethyl-phenyl) -acrylamide;

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-benzyl-5-phenyl-oxazol-4-carboxylic acid;

3– {4– [2– (5-Acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-ylcarbamoyl] -5-phenyl-oxazol-2-yl} tert-butyl ester - propionic;

[2– (2-acetyloxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2-methyl-oxazole – 4– carboxylic;

[2– (2-Acetyloxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid;

[2– (2-acetyloxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2-methyl-oxazol – 4– carboxylic;

[2– (2-Acetyloxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-m-tolyl-oxazol-4-carboxylic acid;

[2– (2-Acetyloxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole-4– carboxylic;

2-Chloro-benzyl ester of [2– (2-acetyloxazol-4-ylmethyl) -2H– [1,2,3] triazol-4-yl] -carbamic acid; Y

[2– (5-acetylfuran – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (6-trifluoromethyl-pyridin-2-yl) –oxazol – 4– carboxylic;

where the double bond of acrylamide derivatives mentioned in the above list may be in the configuration (E) - or (Z) - (preferably in the configuration (E) -).

Any reference mentioned above or below of a compound of formula (I) shall also be construed as reference to the salts, especially pharmaceutically acceptable salts, of said compound of formula (I), as appropriate and convenient.

The term "pharmaceutically acceptable salts" refers to non-toxic, inorganic or organic salts and / or base addition salts, Lit. e.g. " Salt selection for basic drugs ", Int. J. Pharm. (1986), 33, 201-217.

When the plural form is used for compounds, salts, pharmaceutical compositions, diseases and the like, it will also be interpreted as meaning a single compound, a salt or the like.

The compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for use as medicaments. In particular, the compounds of formula (I) modulate the ALX receptor, that is, they act as agonists of the ALX receptor, and are useful for the prevention or treatment of diseases that respond to the activation of the ALX receptor such as inflammatory diseases, obstructive diseases of the respiratory tract, allergic conditions, HIV-mediated retroviral infections, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases and amyloid-mediated disorders (especially Alzheimer's disease); They are also useful for modulating immune responses (especially those produced by vaccination). Especially, the compounds of formula (I) are useful for the prevention or treatment of diseases such as inflammatory diseases, obstructive diseases of the respiratory tract, allergic conditions, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases and intermediate disorders by amyloids, (especially Alzheimer's disease).

In particular, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are useful for the prevention or treatment of selected diseases of inflammatory diseases, obstructive diseases of the pathways respiratory and allergic conditions

Inflammatory diseases, obstructive diseases of the respiratory tract and allergic conditions, include, but are not limited to, one, several or all of the following groups of diseases and disorders:

1) Severe lung injury (ALI); acute adult dyspnoea syndrome (ARDS); pulmonary or respiratory tract disease, chronic obstructive pulmonary pneumopathy, (COPD, COAD or COLD), including chronic bronchitis or dyspnea associated with them, emphysema, as well as exacerbation of hyper-reactivity of the respiratory tract as a result of other drug therapy , in particular another drug inhalation therapy. Especially, inflammatory diseases, obstructive diseases of the respiratory tract, and allergic conditions that include COPD, COAD and COLD.

2) Other inflammatory diseases, obstructive airway diseases and allergic conditions that include bronchitis of any type or origin.

3) Other inflammatory diseases, obstructive diseases of the respiratory tract and allergic conditions include bronchiectasis, and pneumoconiosis of any type or genesis.

4) Other inflammatory diseases, obstructive diseases of the respiratory tract and allergic conditions include asthma of any type or genesis, including intrinsic asthma (non-allergic) or extrinsic asthma (allergic), mild asthma, moderate asthma, severe asthma, bronchitic asthma, asthma Exercise-induced, occupational asthma and asthma induced by bacterial infection.

5) In a further embodiment the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are particularly suitable for the prevention or treatment of inflammatory diseases, inflammatory diseases that include a , several or all of the following groups of diseases and disorders:

5a) In particular, inflammatory diseases refers to neutrophil-related disorders, especially neutrophil-related airway disorders that include hyper-neutrophilia because they affect the respiratory tract and / or the lungs. Other disorders related to neutrophils include periodontitis, glomerulonephritis, and cystic fibrosis.

5b) Other inflammatory diseases include skin diseases, such as psoriasis, contact dermatitis, atopic dermatitis, dermatitis herpetiformis, scleroderma, hypersensitive angiitis, urticaria, systemic lupus erythematosus, and epidermolysis.

5c) Other inflammatory diseases also related to diseases or conditions that have an inflammatory component. Diseases or conditions that have an inflammatory component include, but are not limited to, diseases and conditions that affect the eye such as conjunctivitis, dry keratoconjunctivitis, and seasonal conjunctivitis, diseases that affect the nose including allergic rhinitis, and inflammatory diseases in which the Autoimmune reactions are involved or have an autoimmune or etiological component, such as systemic lupus erythematosus, polychondritis, scleroderma, Wegener's granulomatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, Stevens-Johnson syndrome, idiopathic psilosis, inflammatory autoimmune disease of the intestine, (for example, ulcerative colitis and Crohn's disease), endocrine ophthalmopathy, chronic hypersensitive pneumonitis, primary biliary cirrhosis, dry keratoconjunctivitis and seasonal keratoconjunctivitis, interstitial pulmonary fibrosis, arthritic psoriasis and glomerulonephritis.

5d) Other inflammatory diseases in which autoimmune reactions are involved or that have an autoimmune or etiological component include rheumatoid arthritis, Hishimoto's thyroiditis and type I or II diabetes.

In addition, the components of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the prevention or treatment of HIV-mediated retroviral infections.

HIV-mediated retroviral infections include, but are not limited to one, several or all of the following groups of diseases and disorders caused by HIV-1 and HIV-2 strains such as GUN-4v, GUN-7wt, AG204, AG206, AG208, HCM305, HCM308, HCM342, mSTD104, and HCM309.

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the prevention or treatment of cardiovascular disorders.

Cardiovascular disorders refers to one or more disease states of the cardiovascular tree (including the heart) and diseases of the dependent organs. Cardiovascular tree disease and dependent organ diseases include, but are not limited to, heart muscle disorders (cardiomyopathy or myocarditis) such as idiopathic cardiomyopathy, metabolic cardiomyopathy that includes diabetic cardiomyopathy, alcoholic cardiomyopathy, drug-induced cardiomyopathy, ischemic cardiomyopathy , and hypertensive cardiomyopathy; Atheromatous disorders of major blood vessels (macrovascular disease) such as the aorta, coronary arteries, carotid arteries, cerebrovascular arteries, renal arteries, iliac arteries, femoral arteries, and popliteal arteries, toxic disorders, drug-induced , and metabolic (including hypertensive and / or diabetic) disorders of small blood vessels (microvascular disease) such as retinal arterioles, glomerular arterioles, vasa nervorum, cardiac arterioles, and associated with the capillary bed of the eyes, the kidney ,, the heart, and the central and peripheral nervous systems, and rupture of the plaque of atheromatous lesions of the major blood vessels such as the aorta, coronary arteries, carotid arteries, cerebrovascular arteries, renal arteries, iliac arteries , femoral arteries and popliteal arteries.

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the prevention or treatment of neuroinflammation. Neuroinflammation refers to molecular production signaling cells, glial activation and glial activation responses and pathways, proinflammatory cytokines or chemokines, astrocyte activation or astrocyte activation responses and pathways, microglia activation or microglial activation responses and pathways, stress-related oxidative responses, such as nitric oxide synthase production and nitric oxide accumulation, acute phase proteins, synaptophysin loss and Post-Synaptic Density Protein – 95 (PSD – 95), complement cascade components, loss or reduction of synaptic function, protein kinase activity (e.g., death associated with protein kinase activity), knowledge deficit, cell damage (e.g., neuronal cell damage), cell death (e.g., neuronal cell death), and / or amyloid β deposition of amyloid plaques.

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the prevention or treatment of neurological disorders.

In particular, neurological disorders include, but are not limited to, epilepsy, stroke, cerebral ischemia, cerebral palsy, recurrent multiple sclerosis, progressive multiple sclerosis, Alpers disease, amyotrophic lateral sclerosis (ALS), senile dementia, corpuscle dementia of Lewy, Rhett's syndrome, spinal cord trauma, traumatic brain injury, trigeminal neuralgia, glossopharyngeal neuralgia, Bell's palsy, myasthenia gravis, muscular dystrophy, progressive muscular atrophy, hereditary bulbar progressive muscular atrophy, ruptured syndromes or spinal disc prolapse , cervical spondylosis, plexus disorders, thoracic cage destruction syndromes, peripheral neuropathies, mean cognitive decline, Alzheimer's disease, Parkinson's disease, and Huntington's chorea

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are useful for the prevention or treatment of pain. Pain includes, but is not limited to, neuropathic pain exemplified by conditions such as diabetic neuropathy, post-herpetic neuralgia, trigeminal neuralgia, painful diabetic polyneuropathy, post-stroke stroke, post-amputation pain, myelopathic pain or radiculopathy, facial pain Atypical and causal syndromes.

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the prevention or treatment of prion-mediated diseases. Prion-mediated diseases, also known as transmissible spongiform encephalopathies (TSEs), which include but are not limited to, kuru, Gerstmann – Sträussler– Scheinker syndrome (GSS), Fatal Family Insomnia (FFI) and Creutzfeldt – Jakob Disease (CJD) .

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the treatment of amyloid-mediated disorders. Amyloid-mediated disorders are defined as diseases and disorders, which are caused by association with amyloid or amyloid-like proteins. Diseases and disorders caused by association with amyloid or amyloid-type proteins include, but are not limited to Alzheimer's disease (AD), which includes diseases or conditions characterized by loss of cognitive memory capacity, such as, for example, moderate cognitive impairment (MCI); dementia with Lewy corpuscles; Down's Syndrome; cerebral hemorrhage with amyloidosis. In another embodiment, diseases and disorders caused by amyloid or amyloid-type proteins include progressive supranuclear paralysis, multiple sclerosis, Creutzfeld Jakob disease, Parkinson's disease, HIV-related dementia, Amyotrophic Lateral Sclerosis (ALS), myositis including corpuscles, (IBM), Initial Adult Diabetes, and senile cardiac amyloidosis.

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the modulation of immune responses.

Modulation of immune responses includes, but is not limited to, procedures based on the administration to a subject of at least one antigen composition and at least one compound of formula (I) according to any of the embodiments 1) to 40), or pharmaceutically acceptable salts thereof. In some cases, the antigen-containing composition is administered first, followed by administration of a composition of at least one compound of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof. . In other cases, the antigen-containing composition is finally administered. The different compositions can be administered simultaneously, consecutively, or separated over time. These procedures and compositions are provided for therapeutic and prophylactic immunization (ie, the deliberate provocation, increase, intensification or modulation of an innate and / or adaptive immune response). Particular advantages may include one or more of the following:

1) An accelerated immune response after administration of at least one compound of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, and the antigen, as compared to an administration antigen unique;

2) A greater sensitivity to small amounts of antigen (for example, toxin or pathogen) or antigens that do not usually induce resistant immune responses; Y

3) More effective anti-tumor therapies.

In addition, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the prevention or treatment of cystic fibrosis, pulmonary fibrosis, pulmonary hypertension, cure treatment. of wounds, diabetic nephropathy, reduction of inflammation in tissue transplants, inflammatory diseases caused by pathogenic organisms.

Especially, the compounds of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof, are suitable for the prevention or treatment of diseases selected from one, several or all of the following groups of diseases and disorders:

1) Inflammatory diseases, obstructive diseases of the respiratory tract and allergic conditions such as severe lung injury (ALI); acute adult dyspnoea syndrome (ARDS); and asthma of any type or origin, including intrinsic (non-allergic) asthma extrinsic (allergic) asthma, mild asthma, moderate asthma, severe asthma, asthmatic bronchitis, exercise-induced asthma, occupational asthma and induced asthma followed by bacterial infection ;

2) Inflammatory diseases such as neutrophil-related disorders, especially neutrophil-related airway disorders including hyper-neutrophilia that affects the airways and / or lungs; periodontitis; glomerulonephritis, cystic fibrosis, and skin diseases such as psoriasis, contact dermatitis, atopic dermatitis, dermatitis herpetiformis, scleroderma, hypersensitive angiitis, urticaria, systemic lupus erythematosus, and epidermolysis;

3) Diseases that have an inflammatory component such as diseases and conditions that affect the eyes such as conjunctivitis, dry keratoconjunctivitis, and seasonal conjunctivitis, inflammatory disease in which autoimmune reactions are involved or which have an autoimmune or etiological component; and autoimmune inflammatory bowel disease (for example, ulcerative colitis and Crohn's disease);

4) HIV-mediated retroviral infections such as diseases and disorders caused by strains of HIV-1 and HIV-2, such as GUN-4v, GUN-7wt, AG204, AG206, AG208, HCM305, HCM308, HCM342, mSTD104, and HCM309 ;

5) Neuroinflammation which refers to the production of cellular signaling molecules, glial activation or glial activation responses and pathways, proinflammatory chemokines or cytokines, astrocyte activation or astrocyte responses and pathways, microglia activation or responses and microgial activation pathways, stress-related oxidative responses such as amyloid β deposition of amyloid plaques;

6) Neurological disorders such as stroke, cerebral ischemia, Alzheimer's disease, and Parkinson's disease;

7) Prion-mediated diseases, also known as spongiform encephalopathies (TSEs), such as kuru, Gerstmann – Sträussler – Scheinker Syndrome (GSS), Family Fatal Insomnia (FFI) and Creutzfeldt – Jakob Disease (CJD);

8) Amyloid-mediated disorders;

9) Cystic fibrosis, wound healing treatment and inflammatory diseases caused by pathogenic organisms.

The invention also relates to the use of a compound of formula (I) according to any of embodiments 1) to 40) for the preparation of pharmaceutical compositions for the treatment and / or prophylaxis of the aforementioned diseases.

The present invention also relates to pharmaceutically acceptable salts and pharmaceutical compositions and formulations of compounds of formula (I) according to any of embodiments 1) to 40).

A pharmaceutical composition according to the present invention containing at least one compound of formula (I) according to any of embodiments 1) to 40) (or pharmaceutically acceptable salts thereof) as well as the active agent and optionally carriers and / or diluents and / or adjuvants.

The compounds of formula (I) according to any of embodiments 1) to 40) and their pharmaceutically acceptable salts may be used as medicaments, for example, in the form of pharmaceutical compositions for enteral or parenteral administration.

The production of the pharmaceutical compositions can be carried out in a known manner to any person skilled in the art (see for example, Remington, The Science and Practice of Pharmacy, 21st Edition (2005), Part 5, "Pharmaceutical Manufacturing" [published by Lippincott Williams &amp.; Wilkins]) by describing compounds of formula (I) or their pharmaceutically acceptable salts, optionally in combination with other therapeutically valuable substances, in a form of galenic administration in conjunction with therapeutically compatible liquid or solid carrier techniques and, if desired, pharmaceutically frequent adjuvants.

The present invention also relates to a method for the prevention or treatment of a disease or disorder mentioned herein comprising the administration to a subject of a pharmaceutically active amount of a compound of formula (I) according to any of embodiments 1) to 40), or pharmaceutically acceptable salts thereof.

Unless relative temperatures are used, the term "approximately" placed before a numerical value "X" refers in the present application to an extended range from X minus 10% of X to X plus 10% of X, and preferably to an extended range from X minus 5% of X to X plus 5% of X. In the particular case of temperatures, the term "approximately" placed before a "Y" temperature refers herein to an extended range from the temperature Y minus 10 ° C to Y plus 10 ° C, and preferably at an extended range from Y minus 5 ° C to Y plus 5 ° C. In addition, the term "room temperature" (rt) as used herein refers to a temperature of approximately 25 ° C.

The compounds of Formula (I) can be manufactured by the procedures given herein, by the procedures given in the Examples or by analogous procedures. The optimal reaction conditions may vary with the particular reactants and solvents that are used, but such conditions can be determined by one skilled in the art by usual optimization procedures.

If not indicated against, the generic groups A, E, Q, R1, R2 and R3 are as defined in formula (I). Other abbreviations used are defined in the experimental section. The generic group Ru as used in structures 4b, 4c and 7 below represents hydrogen or C1-C3 alkyl. The generic group Rx as used in structure 4 and

Next 6 represents C1-C2 alkyl or both Rx together form an ethan-1,2-diyl bridge. The generic group Ry as used in structure 4 and 6 below represents (C1-C3) alkyl. The generic group Rz as used in scheme 4 below represents (C1-C4) alkyl. The generic carboxyl R protecting group as used in structure 3 or 5, in the following schemes and in the general procedures of the experimental part represents (C1-C4) alkyl, preferably methyl or ethyl. The generic SiPG group as used in the following structures 4c and 7 represents an appropriate silyl protecting group such as TMS, TIPS, TBDMS or TBDPS, preferably TBDMS.

Reactions of alcohols with methanesulfonyl chloride may result in the formation of the respective chloride or the respective mesylate derivative, depending on the reaction conditions used; it is well known in the art, or that small changes in said reaction conditions may have an influence on the success of said reactions; It should be understood that normally both reagents, chloride and mesylate, should be useful as electrophiles in reactions discussed below.

In some cases the generic groups A, E, Q, R1, R2 and R3 could be incompatible with the set illustrated in the following schemes and will therefore require the use of protective groups (PG). The use of protecting groups is well known in the art (see, for example, "Protective Groups in Organic Synthesis", T.W. Greene, P.G.M. Wuts, Wiley-Interscience, 1999). For the purposes of this discussion, it will be assumed that such protecting groups are necessary in place.

A. Synthesis of the final products

Sections A.a) to A.d) describe below general procedures for the preparation of compounds of formula (I).

Aa) The compounds of formula (I) can be prepared from amines of structure 1 by reaction with the appropriate chloroformate R1-E-COCl (E represents * -alkyl (C1-C4) -O-) at a temperature of approximately room temperature or the appropriate carboxylic acid chloride of formula R1-E-COCl (E represents an oxazole or thiazole radical as defined in formula (I) or -CH = CH-) at a temperature of approximately room temperature in a appropriate solvent such as CH2Cl2 in the presence of a base such as Et3N or DIPEA. If it is not commercially available, the appropriate chloroformate can be prepared at a temperature of approximately room temperature from the corresponding alcohol by reaction with phosgene in an appropriate solvent such as CH2Cl2 in the presence of a base such as Et3N. If it is not commercially available, the appropriate carboxylic acid chloride may be prepared at a temperature of approximately room temperature from the corresponding carboxylic acid by reaction with a reagent such as oxalyl chloride in the presence of DMF in an appropriate solvent such as toluene. . Alternatively, the amines of structure 1 can be coupled with the corresponding carboxylic acid of formula R1-E-COOH using conventional amide coupling conditions such as EDC / HOBt / DMAP, TBTU, HBTU or PiBOP in the presence of a base such as DIPEA or Et3N at a temperature of about room temperature in an appropriate solvent such as CH2Cl2. In case E represents * -C1-C4-O-alkyl, the amines of structure 1 can be coupled with the corresponding alcohol of formula R1-E-H by activation of the compounds of structure 1, for example, with chloroformate of 4-nitrophenyl in an appropriate solvent such as AcCN in the presence of a base such as Et3N or DIPEA or, alternatively, by in-situ formation of the chloroformate from R1-E-H (E represents * -C1-C4-O alkyl -) with, for example, phosgene in an appropriate solvent such as CH2Cl2 in the presence of a base such as Et3N or DIPEA.

Structure 1 Structure 2

The compounds of structure 1 can be obtained from compounds of structure 2 by reduction of the nitro group or by hydrogenation in the presence of a catalytic metal such as Pd / C, Pt / C or PtO2 at a temperature of approximately room temperature in a suitable solvent such as MeOH or EtOH, or by reduction with a metal such as iron in a solvent mixture such as H2O / EtOH in the presence of ammonium chloride at a temperature in the range of from room temperature to 95 ° C.

A.b) Alternatively, the compounds of formula (I) where R2 represents -CO-(C1-C3) alkyl can be prepared by a sequence comprising:

•

Reduction of an ester of structure 3 to the corresponding alcohol under standard reduction conditions using a reagent such as NaBH4 in a solvent such as MeOH at a temperature of approximately room temperature or alternatively, a reagent such as DiBAL in a solvent such as THF at a temperature in the range from about –78 ° C to room temperature;

•

Oxidation of the alcohol to the corresponding aldehyde under standard oxidative conditions using reagents such as MnO2, pyridinium chlorochromate or NMO / TPAP in a solvent such as AcCN or CH2Cl2 at a temperature of approximately room temperature;

•

Addition of a Grignard alkyl reagent at a temperature below room temperature (preferably about –78 ° C) in a solvent such as THF, or, alternatively, addition of a reagent

trialkylammonium at a temperature of about 0 ° C in a solvent such as CH 2 Cl 2 providing the corresponding secondary alcohol; Y

• Oxidation of an alcohol under standard oxidative conditions using reagents such as TPAP / NMO or MnO2 in a solvent such as CH2Cl2 or AcCN at a temperature of approximately room temperature to provide the compound of formula (I).

Structure 3

A.c) Alternatively, the compounds of formula (I) can be prepared by deprotection of a ketal of structure 4 using standard conditions such as:

•

using an acid such as aqueous HCl diluted in a solvent such as THF at a temperature of about room temperature, or

•

using a SCX silica gel in a solvent such as MeOH; or

•

using a silica gel attached to an acid such as tonic acid in a solvent such as MeOH; or

•

using an acid such as formic acid in a solvent such as water at a temperature in the range of from about 0 ° C to about 50 ° C.

Rx Rx

Structure 4

A.d) Alternatively, the compounds of formula (I) where R2 represents -CO-C1-C3 alkyl) can be prepared both by:

• Oxidation of an alcohol of structure 4b (Ru represents (C1-C3) alkyl)) under standard oxidative conditions using reagents such as TPAP / NMO or MnO2 in a solvent such as CH2Cl2 or AcCN at a temperature of approximately room temperature;

or by:

• The oxidation – addition – oxidation sequence described in the last three stages under A.b) from an alcohol of structure 4b (Ru represents hydrogen).

4b structure

B. Synthesis of intermediaries:

Compounds of 2 where R2 represents -CO-(C1-C3) alkyl can be prepared from compounds of structure 5 following the procedure as described in section Ab) or from compounds of structure 6 following the procedure described in Section Ac) above. The compounds of structure 2 where R2 represents -CF2-C1-C3 alkyl can be prepared from compounds of structure where R2 represents -CO-C1-C3 alkyl with a fluorinating agent such as sulfur (diethylamino) sulfur trifluoride or trifluoride of (bis (2-methoxyethyl) amino) sulfur in a solvent such as toluene at a temperature of about 60 ° C.

Compounds of structure 2 where A represents oxazol-2,4-diyl can be prepared by reacting methanesulfonic acid 4-acetyloxazol-2-ylmethyl ester with 4-nitro-2H- [1,2,3] triazole in the presence of a base such as K2CO3 or Cs2CO3 in a solvent such as acetone or AcCN at a temperature approximately from room temperature or 80 ° C (with or without the addition of tetrabutylammonium bromide). Alternatively, the reaction can be prepared in the presence of a base such as DIPEA in a solvent such as DMF, acetone or a mixture of both at a temperature of about room temperature or 50 ° C.

The compounds of structure 2 where A represents isoxazol-2,4-diyl can be prepared by reacting 1– (5-chloromethyl-isoxazol-3-yl) -ethanone with 4-nitro-2H- [1,2,3] triazole in the presence of a base such as K2CO3 or Cs2CO3 in a solvent such as acetone or AcCN at a temperature of about room temperature or 80 ° C (with or without the addition of tetrabutylamine bromide onium). Alternatively, the reaction can be carried out in the presence of a base such as DIPEA in a solvent such as DMF, acetone or a mixture of both at a temperature of about room temperature or 50 ° C.

In a more general way:

The compounds of structure 2 can be prepared by reacting Ms-O-CH2-A-C (O) -alkyl (C1-C3) or Cl-CH2-A-C (O) -alkyl (C1-C3) (especially 1 - (5-Chloromethyl-isoxazol-3-yl) -ethanone or 4-acetyloxazol-2-yl methyl ester of methanesulfonic acid with 4-nitro-2H- [1,2,3] triazole in the presence of a base such as K2CO3 or Cs2CO3 in a solvent such as acetone or AcCN at a temperature of about room temperature or 80 ° C (with or without the addition of tetrabutylammonium bromide) Alternatively, the reaction can be carried out in the presence of a base such as DIPEA in a solvent such as DMF, acetone or a mixture of both at a temperature of about room temperature or 50 ° C.

Compounds of structure 2 where R2 represents -SO2-(C1-C3) alkyl can be prepared by reacting 4-nitro-2H- [1,2,3] triazole (TE Eagles et al. Organic preparations and procedures 2 (2) , 117–119, 1970, PN Neuman

J. Heterocycl. Chem. 8, 51–56, 1971) in the presence of a base such as K2CO3 or Cs2CO3 (with or without the addition of tetrabutylammonium bromide) in a solvent such as acetone or AcCN at a temperature of approximately room temperature or 80 ° C with Cl – CH 2 – A – SO2 – (C1 – C3) alkyl (especially 2-chloromethyl-5-methanesulfonyl-furan). Alternatively, the reaction can be carried out in the presence of a base such as DIPEA in a solvent such as DMF, acetone or a mixture of both at a temperature of about room temperature or 50 ° C.

The compounds of structures 3 and 4 can be prepared analogously with the procedures described in section A.a) from compounds of structure 5 and 6 respectively.

Rx

Rx OR

OR R N ONA OO2N N NNA

O2N Ry N

Structure 5 Structure 6

The compounds of structure 4b can be prepared from the respective compounds of structure 3 by the first stage (Ru represents hydrogen) or the first three stages (Ru represents C1-C3 alkyl) of the sequence described in A.b). Alternatively, the compounds of structure 4b can be prepared from the respective compounds of structure 4c by silyl deprotection using TBAF in a solvent such as THF.

4c structure

The compounds of structure 4c can be prepared analogously to the procedures described in section A.a) from compounds of structure 7

O2N

Structure 7

Compounds of structure 5 may be prepared by reacting 4-nitro-2H- [1,2,3] triazole (TE Eagles et al. Organic preparations and procedures 2 (2), 117-119, 1970, PN Neuman J. Heterocycl. Chem. 8, 51–56, 1971) with, for example, a commercially available 5-chloromethyl-furan-2-carboxylic acid ester (A represents furan-2,5-diyl) or 5-bromo-pentanoic acid ester commercially available (A represents propan-1,3-diyl) or 4-chloromethyl-thiazol-2-carboxylic acid ester (A represents thiazol-2,4-diyl). The reaction can be carried out in the presence of a base such as K2CO3 or Cs2CO3 in a solvent such as acetone or AcCN at a temperature of about room temperature or 80 ° C with the addition of tetrabutylammonium bromide, where appropriate. Alternatively, the reaction can be carried out in the presence of a base such as DIPEA in a solvent such as DMF, acetone or a mixture of both at a temperature of about room temperature or 50 ° C.

Compounds of structure 6 may be prepared analogously to those of structure 5 using In case A represents furan-2,5-diyl, an appropriate furan derivative such as 2– (5-chloromethyl-furan-2-yl) –2 – methyl– [1,3] dioxolane or, if A represents propan – 1,3-diyl, a protected 4-bromo-butyl ketone derivative such as 2– (4 – bromo-butyl) –2– methyl– [1,3] dioxolane or, in case A represents thiophene-2,5-diyl, an appropriate protected thiophene derivative such as 2– (5-chloromethyl-thiophene-2-yl) –2-methyl– [ 1,3] dioxolane or, if A represents phenyl-1,3-diyl, an appropriate protected phenyl derivative such as ester 3– (2-methyl– [1,3] dioxolan-2-yl) -benzyl of methanesulfonic acid, or in case A represents pyridin-2,6-diyl, an appropriate protected pyridine derivative such as ester 6– (2-methyl– [1,3] dioxolan-2-yl) -pyridin-2-ylmethyl of methanesulfonic acid, in case A represents pyridin-2,4-diyl, a protected pyridine derivative such as ester 4– (2-methyl– [1,3] dioxolan-2-yl) -pyridin-2-ylmethyl of methanesulfonic acid or ester 2– (2 –Methyl– [1,3] ddioxolan – 2-yl) –pyridin – 4-ylmethyl of methanesulfonic acid or in case A represents thiazole – 2,4-diyl, an appropriate protected thiazole derivative such as ester 4– (2 –Methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl of methanesulfonic acid or 4-chloromethyl – 2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole or, in case A represents thiophene-2,4-diyl, an appropriate protected thiophene derivative such as 2– (4-chloromethyl-thiophene-2-yl) -2-methyl– [1,3] dioxolane or 2– (5 -Chloromethyl-thiophene-3-yl) -2-methyl- [1,3] dioxolane or, in case A represents thiazole-2,5-diyl, an appropriate protected thiazole derivative such as ester 5- (2-methyl - [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl of methanesulfonic acid oo 5-chloromethyl-2– (2-methyl– [1,3] ddioxolan-2-yl) -thiazole or, in case A represents oxazole-2,5-diyl, an appropriate protected oxazole derivative such as 2– chloromethyl – 5– (2-methyl– [1,3] ddioxolan – 2-yl) –oxazole, or other appropriate reagent of formula Ms – O – CH2 – A– C (ORx) 2-alkyl (C1 – C3) or Cl – CH2 – A – C (ORx) 2 – (C1 – C3) alkyl.

The compounds of structure 6 can also be obtained from the compounds of structure 2 where R2 represents -CO-(C1-C3) alkyl using a reagent such as ethylene glycol in the presence of a reagent such as TsOH in a solvent such as toluene a a temperature of about 110 ° C; or from the compounds of structure 2 where R2 represents -CO-C1-C3 alkyl using reagents such as LiBF4 and trimethyl orthoformate in a solvent such as ethylene glycol at a temperature of about 95 ° C.

Alternatively, the compounds of structure 6 can be synthesized from compounds of structure 5 analogously to the sequence described in section Ab), followed by protection of the keto function using a reagent such as ethylene glycol in the presence of such a reagent as TsOH in a solvent such as toluene at a temperature of about 110 ° C. Alternatively, ketal formation can be carried out using reagents such as LiBF4 and trimethyl orthoformate in a solvent such as ethylene glycol at a temperature of about 95 ° C.

Compounds of structure 7 can be prepared from commercially available 4-nitro-2H- [1,2,3] triazole (TE Eagles et al. Organic preparations and procedures 2 (2), 117-119, 1970, PN Neuman J. Heterocycl. Chem. 8, 51–56, 1971) analogously to structure 5 using, in case A represents oxazol-2,5-diyl, an oxazole derivative such as 2– [1– (ter– butyldimethyl-silanyloxy) -ethyl] -5-chloromethyl-oxazole or, in case A represents oxazol-2,4-diyl, an appropriate protected oxazole derivative such as ester 2– (tert-butyldimethyl- silanyloxymethyl) –oxazole-4 -Methylsulfonic acid methylmethyl.

2– (5 – Chloromethyl – furan – 2 – yl) –2 – methyl– [1,3] dioxolane can be prepared using the following sequence: a) protection of commercially available 1-furan-2-yl-ethanone in the presence of trimethyl orthoformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of about 95 ° C; b) lithiation with an organolithium reagent such as n-butyllithium in a solvent such as THF at a temperature of about -78 ° C and a subsequent addition of DMF; c) reduction with a reducing agent such as MeOH at a temperature of about 0 ° C; and d) alcohol chlorination using for example methanesulfonyl chloride in the presence of a base such as Et3N and DMAP in a solvent such as CH2Cl2 at a temperature of about 0 ° C.

1– (5-Chloromethyl-isoxazol-3-yl) -ethanone can be prepared using the following sequence: a) 5-hydroxymethyl-isoxazole-3-carboxylic acid ethyl ester protection using, for example, tert-butyldimethylsilyl chloride in presence of a base such as imidazole in a solvent such as THF; b) reduction with reducing agent such as DiBAL in a solvent such as THF at a temperature below room temperature; c) oxidation of alcohol under conventional oxidative conditions using reagents such as MnO2 in a solvent such as AcCN at a temperature of approximately room temperature; d) addition of trimethylaluminum at a temperature of about 0 ° C in a solvent such as CH2Cl2; e) oxidation of alcohol under conventional oxidative conditions using reagents such as MnO2 in a solvent such as AcCN at a temperature of approximately room temperature; f) protection of the silyl protecting group in the presence of trimethyl orthoformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of about 95 ° C; g) chlorination of an alcohol using for example or methanesulfonyl chloride in the presence of a base such as Et3N and DMAP in a solvent such as CH2Cl2 at a temperature of about 0 ° C.

2– (5 – Chloromethyl – thiophene – 2 – yl) –2 – methyl– [1,3] dioxolane can be prepared using the following sequence: a) lithiation of 2-methyl-2-thiophene-2-yl– [1 , 3] commercially available dioxolane with an organolithium reagent such as n-butyllithium in the presence of N, N, N ', N'-tetramethyl-ethylenediamine in a solvent such as THF at a temperature of about -78 ° C and a subsequent DMF addition; b) reduction with a NaBH4 reducing agent in a solvent such as MeOH at a temperature of about 0 ° C; c) chlorination of the alcohol using for example methanesulfonyl chloride in the presence of a base such as Et3N and DMAP in a solvent such as CH2Cl2 at a temperature of about 0 ° C.

Ester 6– (2-methyl– [1,3] ddioxolan-2-yl) -pyridin-2-ylmethyl methanesulfonic acid can be prepared using the following sequence: a) reaction of commercially available 2,6-dibromopyridine with a reagent organolithium such as n-butyllithium in a solvent such as ether at a temperature of about -78 ° C and subsequent acetylation with N, N-dimethylacetamide at a temperature in the range of from -78 ° C to room temperature; b) ketal formation in the presence of trimethylformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of about 95 ° C; c) lithium ion with an organolithium reagent such as n-butyllithium in a solvent such as ether at a temperature of about –78 ° C and subsequent DMF formulation; d) reduction with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of about room temperature; e) mesylation using a reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

Ester 2– (2-methyl– [1,3] ddioxolan-2-yl) -pyridin-4-ylmethyl methanesulfonyl acid can be prepared using the following sequence: a) reaction of commercially available 2,4-dibromopyridine with a reagent organolithium such as n-butyllithium in a solvent such as ether at a temperature of about -78 ° C and subsequent acetylation with N, N-dimethyl-formamide at a temperature in the range of -78 ° C at room temperature; b) reduction with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of approximately room temperature; c) protection of alcohol using tert-butyldimethylsilyl chloride in the presence of a base such as imidazole in a solvent such as dichloromethane; d) reaction of the protected alcohol with an organolithium reagent such as n-butyllithium in a solvent such as ether at a temperature of approximately –78 ° C and subsequent acetylation with N, N-dimethylacetamide at a temperature in the range of –78 ° C at room temperature; e) ketal formation in the presence of trimethyl orthoformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of about 95 ° C; f) deprotection of the silyl protecting group under conventional conditions such as TBAF in a solvent such as THF at a temperature of about room temperature or 0 ° C; g) mesylation using a reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

2– (4-Bromo-butyl) –2-methyl– [1,3] dioxolane can be prepared by reacting commercially available 1-methylcyclopentanol with bromide in the presence of a base such as K2CO3 in a solvent such as chloroform at a temperature of approximately 0 ° C followed by protection with ethylene glycol in the presence of a catalyst such as TsOH.

Ester 3– (2-methyl– [1,3] ddioxolan – 2-yl) –benzethyl methanesulfonic acid can be prepared as described for ester 6– (2-methyl– [1,3] ddioxolan – 2-yl) -Pyridin-2-ylmethyl methanesulfonic acid but from commercially available 1,3-dibromobenzene.

Ester 4– (2-methyl– [1,3] ddioxolan-2-yl) -pyridin-2-ylmethyl methanesulfonic acid can be prepared as described for ester 6– (2-methyl– [1,3] dioxiolan– 2-yl) -pyridin-2-ylmethyl methanesulfonic acid but from commercially available 2,4-dibromopyridine.

Methanesulfonic acid 2-acetylpyridin-4-ylmethyl ester can be prepared by the following sequence: a) reaction of commercially available 2,4-dibromopyridine with an organolithium reagent such as n-butyllithium in a solvent such as ether at a temperature of approximately –78 ° C and subsequent formulation with N, N- dimethylformamide; b) reduction with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of approximately room temperature; c) protection in the presence of a silyl protective agent such as tert-butyldimethylsilyl chloride in a solvent such as CH2Cl2 in the presence of a base such as imidazole; d) lithiation with an organolithium reagent such as n-butyllithium in a solvent such as ether at a temperature of approximately -78 ° C and subsequent acetylation with N, N-dimethylacetamide; e) deprotection of the silyl ether derivative using a fluorinating agent such as TBAF in a solvent such as THF at a temperature of approximately room temperature; and f) mesylation using a reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

Ester 4– (2-methyl– [1,3] ddioxolan-2-yl) -thiazol-2-ylmethyl methanesulfonic acid can be prepared as described for ester 2– (2-methyl– [1,3] ddioxolan –2 – il) –pyridin – 4-ylmethyl of methanesulfonic acid but from commercially available 2,4-dibromo-thiazole.

2– (4 – Chloromethyl – thiophene – 2 – yl) –2 – methyl– [1,3] dioxolane can be prepared as described for 2– (5– chloromethyl-furan – 2-yl) –2 – methyl– [1,3] dioxolane but from 1– (4 – bromo – 2 – thienyl) –etan – 1 – one commercially available.

4-Chloromethyl-thiazole-2-carboxylic acid ethyl ester can be prepared following the following sequence: a) reaction of commercially available oxalamic acid ethyl ester with a Lawesson reagent in a solvent such as toluene at a temperature of approximately 80 ° C; and b) cyclization with 1,3-dichloroacetone in a solvent such as toluene at a temperature of approximately 110 ° C.

4 – Chloromethyl – 2– (2-methyl– [1,3] ddioxolan – 2-yl) -thiazole can be prepared from 4-chloro-methyl-thiazole-2-carboxylic acid ethyl ester by the sequence described in Ab) followed by ketal formation in the presence of trimethyl orthoformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of approximately 90 ° C.

2-Chloromethyl-5-methanesulfonyl-furan can be prepared by the following sequence: a) reaction of 5-nitro-furan-2-carboxylic acid ethyl ester with sodium methantiolate in a solvent such as DMSO at a temperature of approximately 100 ° C; b) oxidation with an oxidizing agent such as, m-CPBA in a solvent such as CH2Cl2 at a temperature of approximately room temperature; c) reduction with a reducing agent such as DiBAL in a solvent such as THF at a temperature below room temperature; and d) chlorination using a reagent such as methanesulfonyl chloride in a solvent such as dichloromethane in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

Ester 5– (2-methyl– [1,3] ddioxolan-2-yl) -thiazol-2-ylmethyl methanesulfonic acid can be prepared by the following sequence: a) commercially available 2-bromo-thiazole-5-carbaldehyde reaction with trimethylaluminum in a solvent such as dichloromethane at a temperature of about 0 ° C; b) oxidation with an oxidizing people such as MnO2 in a solvent such as acetonitrile at a temperature of approximately room temperature; c) ketal formation in the presence of trimethyl orthoformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of about 95 ° C; d) lithiation with an organo lithium reagent such as n-butyl lithium in a solvent such as ether at a temperature of about -78 ° C and subsequent formulation with N, N-dimethylformamide; e) reduction with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of approximately room temperature; f) mesylation using a reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

5-Chloromethyl – 2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole can be prepared by the following sequence: a) reduction of commercially available 2-bromo-thiazole-5-carbaldehyde with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of about room temperature; b) protection of alcohol using tert-butyldimethylsilyl chloride in a solvent such as CH2Cl2 in the presence of a base such as imidazole; c) lithiation with an organolithium reagent such as n-butyllithium in a solvent such as ether at a temperature of approximately -78 ° C and subsequent acetylation with N, N-dimethylacetamide; d) ketal formation in the presence of trimethyl orthoformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of about 95 ° C; e) deprotection of the derivative or silyl derivative ether using a fluorinating agent such as TBAF in a solvent such as THF at a temperature of approximately room temperature; and f) chlorination using a reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

2– (5 – Chloromethyl – thiophene – 3-yl) –2 – methyl– [1,3] dioxolane can be prepared as described for 5-chloromethyl – 2– (2-methyl– [1,3] dioxolan – 2 –Il) –thiazole but from 4 – bromo – thiophene – 2 – carbaldehyde commercially available.

Methanesulfonic acid 4-acetyloxazol-2-ylmethyl ester can be prepared by the following sequence: a) formation of oxazole with commercially available 3-phenyl-acrylamide reaction with 3-bromo-2-oxo-propionic acid ethyl ester in the presence of a base such as NaHCO3 in a solvent such as THF at a temperature around 60 ° C; b) decomposition or xidative using for example NaIO4 supported on silica gel and a metal complex such as RuCl3 hydrate in a solvent such as dichloromethane at a temperature of approximately room temperature; c) reduction with a reducing agent such as NaBH4 in a solvent such as EtOH at a temperature of about 0 ° C; d) protection of alcohol using tert-butyldimethylsilyl chloride in a solvent such as CH2Cl2 in the presence of a base such as imidazole; e) reduction of the aldehyde with a reducing agent such as DiBAL in a solvent such as CH2Cl2 at a temperature of about -78 ° C; f) reaction with trimethylamino minium in a solvent such as dichloromethane at a temperature of about 0 ° C; g) oxidation with an oxidizing agent such as MnO2 in a solvent such as acetonitrile at a temperature of approximately room temperature; h) deprotection of the silyl ether derivative using a fluorinating agent such as TBAF in a solvent such as THF at a temperature of approximately room temperature; and i) mesylation using a reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

Ester 2– (tert-butyldimethyl-silanyloxymethyl) –oxazol-4-ylmethyl methanesulfonic acid can be prepared by the following sequence: a) formation of oxazole with a commercially available 3-phenyl-acrylamide reaction with 3-bromine acid ethyl ester– 2-oxo-propionic in the presence of a base such as NaHCO3 in a solvent such as THF at a temperature of about 60 ° C; b) oxidative decomposition using for example NaIO4 supported on silica gel and a metal complex such as RuCl3 hydrate in a solvent such as CH2Cl2 at a temperature of approximately room temperature; c) reduction with a reducing agent such as NaBH4 in a solvent such as EtOH at a temperature of about 0 ° C; d) protection of alcohol using tert-butyldimethylsilyl chloride in a solvent such as CH2Cl2 in the presence of a base such as imidazole; e) reduction of alcohol with a reducing agent such as DiBAL in a solvent such as THF at a temperature of

about 0 ° C; f) mesylation using an active reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

2– [1– (tert-Butyldimethyl-silanyloxy) -ethyl] -5-chloromethyl-oxazole can be prepared using the following sequence: a) commercially available oxazole reaction with an organo magnesium reagent such as isopropyl magnesium chloride in a solvent such as THF at a temperature of approximately -15 ° C and subsequent acetylation with N-methoxy-N-methyl acetamide at a temperature in the range of from -15 ° C to rt; b) reduction with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of approximately room temperature; c) protection of alcohol using tert-butyldimethylsilyl chloride in the presence of a base such as imidazole in a solvent such as THF; d) reaction of the protected alcohol with an organolithium reagent such as t-butyllithium in a solvent such as THF at a temperature in the range of –78 ° C to –40 ° C and subsequent formulation with N, N-dimethyl– formamide at a temperature in the range of –78 ° C to rt; e) reduction with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of approximately room temperature; g) chlorination using a reagent such as methanesulfonyl chloride in a solvent such as CH2Cl2 in the presence of a base such as Et3N and DMAP at a temperature of about 0 ° C.

2-Chloromethyl-5– (2-methyl– [1,3] ddioxolan-2-yl) -oxazole can be prepared using the following sequence: a) commercially available oxazole lithiation with an organolithium reagent such as n-butyllithium in a solvent such as THF at a temperature of about –78 ° C and subsequent and addition of DMF; b) reduction with a reducing agent such as NaBH4 in a solvent such as MeOH at a temperature of about 0 ° C; c) protection of alcohol using tert-butyldimethylsilyl chloride in the presence of a base such as imidazole in a solvent such as THF; d) lithiation with an organolithium reagent with a reagent such as t-butyllithium in a solvent such as THF at a temperature in the range of –78 ° C to –40 ° C and subsequent DMF formulation at a temperature in the range from –78 ° C to rt; e) reaction with trimethylaluminum in a solvent such as dichloromethane at a temperature of about 0 ° C; f) oxidation with an oxidation agent such as MnO2 in a solvent such as acetonitrile at a temperature of approximately room temperature; g) ketal formation and deprotection of the silyl protecting group in the presence of trimethyl orthoformate and a catalyst such as LiBF4 in a solvent such as ethylene glycol at a temperature of about 95 ° C; h) alcohol chlorination using for example Ms-Cl in the presence of a base such as Et3N and DMAP in a solvent such as CH2Cl2 at a temperature of about 0 ° C.

Acid chloroformates and chlorides of formula R1-E-COCl or carboxylic acids of formula R1-E-COOH are commercially available or synthesized according to well known procedures, for example, from commercially available benzoic acids, benzaldehydes, benzyl alcohols or their heterocyclic analogues.

Acids of formula R1-E-COOH, which are also the compounds of structure 8 are well known in the art or are prepared according to the procedures described below.

Structure 8

Compounds of structure 8 where R 3 represents Me can be prepared as described in Scheme 1 by reacting ester derivatives of 3-oxo-propionic acid with an aqueous solution of sodium nitrite in the presence of an acid such as glacial acetic acid. The subsequent transformation of the oxime with acetic anhydride in the presence of an acid such as glacial acetic acid and catalytic amounts of metal chlorides such as mercury chloride and zinc powder followed by cyclization under dehydration conditions such as thionyl chloride in chloroform followed by Saponification of the ester function using methods known in the art such as treatment with a base such as NaOH in a solvent or a solvent mixture such as ethanol / water or THF provided the desired acid derivative. The respective ester derivatives of 3-oxo-propionic acid are commercially available or well known in the art.

R1

Scheme 1: Synthesis of Oxazol (1).

Alternatively, the compounds of structure 8 can be prepared as described in Scheme 2 by reacting ester derivatives of 3-oxo-propionic acid with a solution of 4-acetamido-benzenesulfonyl azide and a base such as Et3N. Subsequent treatment with a carboxamide derivative and a catalyst such as tetrakis (acetate) dirhodium (II) dihydrate followed by cyclization using triphenylphosphine and iodine in the presence of a base such as Et3N provided the desired acid derivative. The respective ester derivatives of 3-oxo-propionic acid are commercially available or well known in the art.

OR OO OO

R3

OO NH2 R

R R1

R1 O R OR1 OR R3

N + HN N-O

Scheme 2: Synthesis of Oxazol (2).

Alternatively, compounds of structure 8 where R 3 represents hydrogen can be prepared as

10 described in Scheme 2b by reacting a solution of an acid derivative of formula R 1 COOH with methyl isocyanoacetate in the presence of a base such as potassium carbonate sesquihydrate or DIPEA and DPPA in a solvent such as DMF. Saponification of the ester function using methods known in the art such as treatment with a base such as NaOH in a solvent or a solvent mixture such as ethanol / water or THF provided the respective acid derivative. The respective R1COOH acids are commercially

15 available or well known in the art.

Scheme 2b: Synthesis of Oxazol (3).

Alternatively, the compounds of structure 8 can be prepared as described in Scheme 3

by esterification of a 3-phenyl serine derivative using a reagent such as thionyl chloride in a solvent such as MeOH at a temperature of about 0 ° C followed by coupling with an acid derivative

R3-COOH carboxylic acid using conventional conditions such as HOBt, DCC, N-methylmorpholine in a solvent

such as CH2Cl2 at a temperature of about 0 ° C. The oxidation of alcohol with an oxidative reagent such

as a Dess-Martin periodinan in a solvent such as CH2Cl2 followed by cyclization using triphenylphosphine and

iodine in the presence of a base such as Et3N provided the respective oxazole derivative. The desired acid derivatives may be obtained by saponification of the ester function using methods known in the

technique such as treatment with a base such as aqueous LiOH in a solvent such as dioxane.

OH OR OH OR OH OR

RR1 O

R

R1R1 OOH

HN O NH2 NH2 R3

Scheme 3: Synthesis of Oxazol (4).

Compounds of structure 8 where R 1 is an aryl group, said group is substituted by C 1 -C 4 alkoxy-C 1 -C 2 alkyl can be obtained, for example, according to Scheme 4 by a sequence comprising:

•

Saponification of the 5-phenyl-oxazol hydroxy-C1-C2-substituted alkyl derivative (prepared according to Schemes 5 or 6) using methods known in the art such as treatment with a base such as ac LiOH. in a solvent such as THF;

 Alkylation of the corresponding alcohol with an alkyl halide such as alkyl iodide in the presence of a base such as NaH in a solvent such as DMF;

•

Saponification of the resulting ester using a process known in the art such as treatment with a base such as NaOH in a solvent or a solvent mixture such as ethanol / water or THF.

NO

NO NO

NO

Rz

R

OO OOH OO OOH

() n () n () n () n

OH OH O OR

Rz Rz

Scheme 4: Synthesis of 5-phenyl-oxazole (C1-C4) alkoxy-C1-C2-substituted alkyl (RZ represents (C1-C4) alkyl and n represents 1 or 2) derivatives.

5-Phenyl-oxazole derivatives Hydroxy-(C1-C2) alkyl-substituted according to Scheme 5 can be obtained by a sequence comprising:

• Formation of oxazole by reaction of a mono-ester derivative of phenyl-dicarboxylic acid with methyl isocyanoacetate in a manner analogous to the procedure described in Scheme 2b;

• Selective saponification of the phenyl-linked ester group using any of the methods known in the art (for example, by dissociation of catalyzed acid from a tert-butyl ester with, for example, TFA);

• Reduction of the resulting acid to the respective primary alcohol with a reducing agent such as borane; twenty

Scheme 5: Synthesis of 5-phenyl oxazol hydroxy-C1-C2-substituted alkyl derivatives.

Alternatively, 5-phenyl oxazol hydroxy-C1-C2-substituted alkyl derivatives can be obtained, for example, according to Scheme 6 by a sequence comprising:

• Formation of oxazole by reacting a hydroxy-C1-C2 alkyl substituted benzoic acid derivative with methyl isocyanoacetate in a manner analogous to the procedure described in Scheme 2b;

Scheme 6: Synthesis of 5-phenyl oxazol hydroxy-C1-C2-substituted alkyl derivatives (2). 5

Structure 9

The compounds of structure 9 can be prepared by a first reaction of methyl dichloroacetate with a commercially available benzaldehyde derivative R1-CHO in the presence of a base such as KOt-Bu in a solvent such as THF. The desired compounds of structure 9 where R3 represents C1-C4 alkyl or cyclopropyl are obtained as described in Scheme 7 by subsequent transformation (cyclization) with the respective thioamides in a solvent such as MeCN followed by saponification of the ester function using procedures known in the art such as treatment with a base such as NaOH in a solvent such as MeOH. The respective R1-CHO benzaldehydes are commercially available or well known in the art. Thioamides are commercially available or, alternatively, can be synthesized from commercially available carboxamides with a Lawesson reagent.

Scheme 7: Synthesis of thiazole (1), where R3 represents C1-C4 alkyl or cyclopropyl.

Alternatively, the desired compounds of structure 9 where R3 represents hydrogen are obtained as described in Scheme 8 by reaction of methyl dichloroacetate with commercially available benzaldehyde derivatives R1-CHO in the presence of a base such as KOt-Bu in such a solvent. as THF. A subsequent transformation with commercially available thiourea followed by treatment with a base such as sodium bicarbonate provided the amino-thiazole derivative. Sandmeyer transformation using a Cu (II) derivative such as CuBr2 followed by hydrogenation in the presence of a catalytic metal such as Pd / C, Pt / C or PtO2 provided the desired ester. Saponification of the ester function can be carried out using methods known in the art such as treatment with a base such as NaOH in a solvent such as MeOH.

OR OR Cl O RR OR

N

ON ORR1

Br O SR1 S H2NR1 R1

Scheme 8: Synthesis of Thiazole (2).

Provided that the compounds of formula (I) are obtained in the form of mixtures of enantiomers, the enantiomers may be separated using methods known to one skilled in the art, for example, by formation and separation of diastereomeric salts or by HPLC on a chiral stationary phase. such as a Regis Whelk – O1 (R, R) column (10 µm), a Daicel ChiralCel OD – H column (5–10 µm), or a Daicel ChiralPak IA (10 µm) or an AD – H column (5 µm) . Typical conditions of chiral HPLC are an isocratic mixture of eluent A (EtOH, in the presence or absence of an amine such as Et3N or diethylamine) and eluent B (hexane), at a flow rate of

0.8 to 150 ml / min.

Experimental Part

Abbreviations (as used here in the description and in the description above)

Ac AcCl AcCN

acetyl acetylitrile acetyl chloride

25

AcOH

acetic acid

here

aqueous

atm

atmosphere

Boc

tert-butoxycarbonyl

BSA

bovine serum albumin

Bu

butyl

BuLi

n – butyllithium

AC.

approximately

cat.

catalytic

DCC

N, N’ – dicyclohexylcarbodiimide

DIPEA

diisopropylethylamine

DiBAL

di-iso-butylaluminum hydride

DMAP

4-N, N-dimethylaminopyridine

DMF

dimethylformamide

DMSO

dimethyl sulfoxide

DPPA

diphenyl phosphoryl azide

EA

ethyl acetate

EIA

immunoassay enzyme

EDC

N- (3-dimethylaminopropyl) –N'-ethyl-carbodiimide hydrochloride

ELSD

evaporative detection by light scattering

eq.

equivalent (s)

ES +

electro-dew, positive ionization

Et

ethyl

ether

diethyl ether

Et3N

triethylamine

EtOH

ethanol

FC

silica gel evaporative column chromatography

h

hours (s)

HBTU

hexa fluorophosphate O– (benzotriazol – 1-yl) –N, N, N ', N'-tetramethyluronium

hept

heptane

HOBt

hydroxybenzotriazole

HPLC

high performance liquid chromatography

LC – MS

liquid chromatography - mass spectrometry

m – CPBA

meta-chloroperbenzoic acid

I

methyl

MeOH

methanol

min

minute (s)

MPLC

medium pressure liquid chromatography

MS

mass spectrometry

Ms Methanesulfonyl

NMO

N-methyl-morpholin-N-oxide

NMR

nuclear magnetic resonance

OAc

acetate

org.

organic

p

for

p – TsOH

para-toluene sulfonic acid

PG

protective group

PiBOP

hexafluor-benzotriazol-1-yl-oxy-tris-pyrrolidine-phosphonium phosphate

Get out of Rochelle

sodium potassium tartrate

rf

retention factor

rt

room temperature

sat.

saturated

SCX

strong cation exchanger

Sun.

solution

TBA

tetra – n – butylammonium

TBAF

tetra-n-butylammonium fluoride

TBDMS

tert-butyldimethyl-silyl

TBDPS

tert-butyldiphenyl-silyl

TBTU

O- (benzotriazol-1-yl) -N, N, N ', N'-tetramethyluronium tetrafluorborate

tBu

tert-butyl, tertiary butyl

TFA

trifluoroacetic acid

THF

tetrahydrofuran

TIPS

tri-isopropyl-silyl

FTA

thin layer chromatography

TMS

trimethyl-silyl

TPAP

tetrapropylammonium perrutenate

tR

holding time

TsOH

p-toluene sulfonic acid monohydrate

UV

ultra violet

Vis

visible

I. Chemistry

General. All temperatures are set in degrees Celsius (° C). Unless otherwise indicated, the reactions are carried out at room temperature.

As a technical SCX, SiliaBond® SCX from Silicycle was used.

Analytical thin layer chromatography (TLC) is carried out with 0.2 mm plates: Merck, silica gel gel 60 F254. Preparative thin layer chromatography (TLC) was carried out with 0.2 or 0.5 mm plates: Merck, silica gel gel 60 F254. The detection was carried out with UV or with a solution of KMnO4 (3 g), K2CO3 (20 g), 5% NaOH (3 ml) and H2O (300 ml) with subsequent heating.

Evaporative column chromatography (FC) and filtration were carried out using 60 Merck silica gel (0.063-0.200mm) or Macherey-Nagel silica gel (0.063-0.200mm); elution with EA, hept, CH2Cl2, CHCl3, MeOH or mixtures thereof.

MPLC was carried out using isolute SPE Flash SI II columns of international sorbent technology, elution with EA, hept, CH2Cl2, MeOH or mixtures thereof.

LC – MS 01 conditions (if not indicated otherwise): Analytical: Thermo Finnigan MSQ Surveyor MS with Agilent 1100 Binary Pump and DAD. Column: Zorbax SB – AQ 5µm, 4.6x50 mm ID from Agilent Technologies. Eluents: A: H2O + 0.04% TFA; B: AcCN; Gradient: 5% B → 95% B for 1 min. Flow 4.50 ml / min. Detection: UV / Vis + MS, tR indicated in min.

Conditions LC – MS – conditions 02 (if not indicated otherwise): Analytical: Thermo Finnigan MSQ Plus MS with Agilent 1100 Binary Pump and DAD. Column: Zorbax SB – AQ 5µm, 4.6x50 mm ID from Agilent Technologies. Eluents: A: H2O + 0.04% TFA; B: AcCN; Gradient: 5% B → 95% B for 1 min. Flow: 4.50 ml / min. Detection: UV / Vis and / or ELSD + MS, tR indicated in min.

LC – MS 05 conditions (if not indicated otherwise): Analytical: Dionex GHP 3200 Binary Pump, MS: Thermo MSQ Plus, DAD: Dionex PDA 3000, ELSD: Sedere Sedex 85. Column: Xbridge C18 5µM, 4.6x50 mm Waters ID, thermostated in the Dionex TCC – 3200 compartment. Eluents: A: H2O + 0.04% TFA; B: AcCN. Procedure: Gradient: 5% B → 95% B for 1.0 min. Flow: 4.5 ml / min. Detection: UV / Vis and / or ELSD, and MS, tR indicated in min.

LC – MS 05b conditions (if not indicated otherwise): Analytical: Dionex GHP 3200 Binary Pump, MS: Thermo MSQ Plus, DAD: Dionex PDA 3000, ELSD: Sedere Sedex 85. Column: Zorbax Extend C18 1.8µM, 4.6x20 mm from Agilent Technologies, thermostated in the Dionex TCC – 3200 compartment. Eluents: A: H2O + 0.04% TFA; B: AcCN. Procedure: Gradient: 5% B → 95% B for 1.0 min. Flow: 4.5 ml / min. Detection: UV / Vis and / or ELSD, and MS, tR indicated in min.

Preparative HPLC: X – Bridge C18 5µm, 50x19 mm Waters ID. Eluents: A: H2O + 0.5% NH4OH; B: AcCN; Gradient: 10% B → 90% B for 5 min. Flow: 40.0 ml / min. Detection: UV / Vis and / or ELSD.

Chiral HPLC, analytical: a) Regis Whelk column, 4.6 x 250 mm, 10 µm. Eluent A: EtOH + 0.05% Et3N. Eluent B: hexane. Flow: 1 ml / min. b) ChiralPak AD, 4.6 x 250 mm, 5 µm. Eluent A: EtOH + 0.05% Et3N. Eluent B: hexane flow. Flow: 1 ml / min. c) ChiralCel OD, 4.6 x 250 mm, 10 µm. Eluent A: EtOH + 0.1% Et3N. Eluent B: hexane. Flow: 0.8 ml / min.

Chiral HPLC, preparative: a) Regis Whelk 01 column, 50 x 250 mm. Flow: 100 ml / min. b) ChiralPak AD, 20 x 250 mm. Flow: 1 ml / min. c) ChiralCel OD, 20 µm, 50 mm x 250 mm. Flow: 100 ml / min.

NMR: Bruker Advance 400 (400 MHz); Varian Mercury 300 (300 MHz); chemical changes are given in ppm in relation to the solvent used; multiplicities: s = singlet, d = doublet, t = triplet, q = quadruplet, p = pentuplete, hex = hextet, hept = heptet, m = multiplet, br = width, coupling constants are given in Hz.

The following examples illustrate the invention but do not limit the scope thereof.

General Procedures

General Procedure A: Amide Coupling:

In a glass jar, under an inert atmosphere (N2), to an acid (1.5 eq.) Weighed in a glass jar, a solution of aminotriazole (1.0 eq.) In CH2Cl2 (0.1M) was added . A solution of HOBt (2.0 eq.), DMAP (0.25 eq.), And DIPEA (2.0 eq.) In CH2Cl2 (10 ml per mmol of HOBt) was added, followed by EDC (1.5 eq.). The resulting mixture was stirred at room temperature overnight. The reaction mixture was poured into a syringe containing diatomaceous earth (Isolute HM-N from Separtis) treated with 1M HCl (1.0 ml per g of Isolute®). The product was eluted with CH2Cl2 (3 × 1 ml) and the solvent was removed under reduced pressure. Purification of the residue by FC or HPLC provided the desired compound.

General Procedure B: Dioxolane Deprotection (1):

In a glass jar, under an inert atmosphere (N2), a 0.07M solution of dioxolane (1.0 eq.) In THF was treated with 1N HCl (2.7 eq.) And the reaction mixture was stirred at temperature ambient until completion. Water was added and the product was extracted twice with EA. The organic layer was dried over MgSO4 filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC or HPLC provided the desired compound.

General Procedure C: Dioxolane Deprotection (2):

To a glass jar containing a 0.05M solution of dioxolane in MeOH was added SCX silica gel (70 mg per 0.05 mmol of dioxolane) and the reaction mixture was stirred at room temperature for 18 h. The mixture was filtered and the solvent was removed under reduced pressure. Purification of the residue by FC or HPLC provided the desired compound.

General Procedure D: Carbamate Formation (1):

Stage 1:

In a glass jar, under an inert atmosphere (N2), a 0.065M solution of alcohol (1.3 eq.) In CH2Cl2 was treated with phosgene (1.3 eq., 20% solution in toluene). The resulting mixture was stirred at room temperature overnight. The reaction mixture was then poured into a syringe containing diatomaceous earth (Isolute HM-N from Separtis) treated with 1M NaOH (1.25 ml per g of Isolute®). The product was eluted with CH2Cl2 (3 × 1 ml) and the solvents were removed under reduced pressure.

Stage 2:

The chloroformate was treated with a solution of the appropriate aminotriazole derivative (1.0 eq.) And DIPEA (2.0 eq.) In CH2Cl2 (20 ml per mmol of aminotriazole derivative) and the resulting mixture was stirred at room temperature overnight. . The reaction mixture was poured into a syringe containing diatomaceous earth (Isolute HM-N from Separtis) treated with 1M HCl (1.0 ml per g of Isolute®). The product was eluted with CH2Cl2 (3 × 1 ml) and the solvent was removed under reduced pressure. Purification of the residue by HPLC provided the desired compound.

General Procedure E: Ester hydrolysis:

A 0.5M solution of the respective carboxylic acid ester (1.0 eq.) In a mixture in a 3: 1 mixture of THF and the corresponding alkyl alcohol, for example, MeOH or EtOH, was treated with aq. NaOH. 1M (2.0 eq.). After stirring for 3 h, a white suspension formed and the organic volatiles were removed under reduced pressure. The remaining mixture was diluted with water (half the amount of the 3: 1 mixture of THF and MeOH), cooled with an ice bath and acidified (pH = 3-4) by adding 1M aqueous HCl. The suspension was filtered and the residue was washed with water to provide the desired carboxylic acid derivative after drying.

General Procedure F: Synthesis of 2-acetylamino-3-oxo-propionic acid ester derivatives:

O o

R R1

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 2.5M solution of the respective ester derivative of 3-oxo-propionic acid (1.0 eq.) In acetic acid The glacial was cooled to 10 ° C and at this temperature an 8.2M solution of NaNO2 (1.16 eq.) in water was added. After the addition was complete (15 min), the solution was allowed to warm to room temperature and stirred for 2 h. The solution was then poured into water (5.3 volume glacial acetic acid) and after a few minutes the crystals began to appear. The suspension was cooled with an ice bath and the crystals were collected by filtration. The cake was washed several times with cold water and the water was removed by azeotropic distillation with toluene under reduced pressure to provide the respective ester derivative of 2-hydroxyimino-3-oxo-propionic acid, which was dissolved in a 1: 1 mixture, 3 of acetic anhydride and glacial acetic acid (0.66 ml for 1.0 mmol of the respective ester derivative of 3-oxo-propionic acid). To this solution was added sodium acetate (0.06 eq.) And HgCl2 (0.002 eq.). The mixture was heated at reflux for 1 h, then cooled to room temperature and filtered. The solid was rinsed with ether, the organic filtrate was recovered, washed 3 times with water and once with 1M aqueous K2CO3. The organic layer was dried over MgSO4, filtered and the solvent was removed under reduced pressure. The crude product was purified by FC to provide the ester derivative of 2-acetylamino-3-oxo-propionic acid.

General Procedure G: Cycling (1):

OO R1 SOCl2

ROR1

OR HN O

OR

NO R

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 1.6M solution of the respective ester derivative of 2-acetylamino-3-oxo-propionic acid (1.0 eq. ) in chloroform it was cooled to about 0 ° C 3 in an ice / NaCl bath. SOCl2 (1.4 eq.) Was added to the stirred solution and the temperature was maintained at about 0 ° C for 30 minutes. Then the solution was stirred at reflux for one hour. Another 0.25 eq. of SOCl2 and the reaction mixture was refluxed for an additional hour. The excess SOCl2 was quenched with K2CO3. 1M aqueous. The aqueous layer was extracted twice with ether. The combined organic phases were washed once with water and dried over MgSO4, filtered and the solvent was removed under reduced pressure to provide the desired oxazole derivative.

General Procedure H: Cycling (2):

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), Et3N (4.1 eq.) Followed by a 0.1M solution of the respective ester derivative of acid 2– (carbonyl -Amino) -3-oxo-propionic (1.0 eq.) In CH2Cl2 were added to a 0.2M solution of triphenylphosphine (2.0 eq.), And iodine (2.0 eq.)

in CH2Cl2. The reaction mixture was stirred for 1.5 h at room temperature. The solvent was removed under reduced pressure and the residue was purified by FC to provide the desired oxazole derivative.

General Procedure I: N – Insertion:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and and under an inert atmosphere (N2), a 0.5M solution of the diazo derivative (1.0 eq.) In 1,2-dichloroethane was added for 1 , 5 h at a reflux solution of the carboxamide derivative (1.0 eq.) And rhodium (II) acetate dihydrate (tetrakis (acetate) dirodium (II), 0.05 eq.) In 1,2-dichloroethane (3 ml per mmol of carboxamide derivative). The reaction mixture was then stirred for 1.5 h at reflux. The solvent was removed under reduced pressure and the residue was purified by FC to provide the desired ester derivative of 2- (carbonyl-amino) -3-oxo-propionic acid ester.

General Procedure J: Diazoation:

OO

OO R

R

R1R1 OO N + N-

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.17M solution of the ester derivative of 3-oxo-propionic acid (1.0 eq.) In AcCN is treated at 0 ° C with n-4-acetamidobenzenesulfonyl azide (1.0 eq.) followed by Et3N (3.0 eq.). The reaction mixture was stirred for 1 h at room temperature. The solvent was removed under reduced pressure, the residue was triturated in light ether-oil and filtered. The solvent was removed under reduced pressure and the residue was purified by FC to provide the desired diazo derivative.

General Procedure K: Claisen Condensation

OO OR RR1R1 OOH

A) In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 1.3M solution of the acid derivative (1.0 eq.) In 1,2-dichloroethane was treated at room temperature with a few drops of DMF followed by oxalyl chloride (1.3 eq.). The reaction mixture was stirred for 3 h at room temperature followed by 20 min at 80 ° C. The solvent was removed under reduced pressure.

B) In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.83M solution of potassium malonic acid monoethyl ester (2 eq.) In acetonitrile was treated at 10 ° C magnesium chloride (2.5 eq.) And the suspension was stirred at 10 ° C for 30 min and at room temperature for 3 h. The reaction mixture was cooled to 0 ° C and treated by dripping for 15 min with the acid chloride solution prepared for A, followed by Et3N (2 eq.). The resulting suspension was stirred at room temperature for 20 h. The solvent was removed under reduced pressure and the residue was extracted with toluene. The residue was extracted with toluene (1.5 ml per mmol of potassium malonic acid monoethyl ester) and treated at 10 ° C with the same amount of 4M HCl as well as toluene. The organic layer was washed twice with 4M HCl, water, dried over MgSO4, filtered and the solvent was removed under reduced pressure. The residue was purified by FC to provide the desired derivative.

General Procedure L: Dioxolane deprotection (3):

To a glass jar containing a 0.05M solution of dioxolane in MeOH was added silica gel bound to tanic acid (70 mg per 0.05 mmol of dioxolane, silica gel R60530B bound to Silicycle acid) and the mixture The reaction was stirred at room temperature for 18 h. The mixture was filtered. Purification of the residue by FC

or HPLC provided the desired compound.

General Procedure M: Cycling (3):

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.5M solution of the acid (1.0 eq.) In DMF was treated at room temperature with carbonate sesquihydrate potassium, or alternatively, DIPEA (from 1.2 eq. to 1.5 eq.) followed by a 2.0M solution of methyl isocyanoacetate (1.5 eq. to 3.2 eq.) in DMF and the mixture was stirred at room temperature for 5 min. The reaction mixture was cooled to 0 ° C and a 0.67M solution of DPPA (1.1 eq.) In DMF was treated. The resulting suspension was stirred at 0 ° C for 2 h and at room temperature for 15 h. It was then poured into a 1: 1 mixture of EA and toluene and the organic layer was washed with water, 10% citric acid, water and saturated aqueous NaHCO3. The organic layer was dried over MgSO4, filtered and the solvent was removed under reduced pressure. The residue was purified by FC to provide the desired derivative.

General Procedure N: Dioxolane Deprotection (4):

In a glass jar, under an inert atmosphere (N2), a 0.1M solution of dioxolane (1.0 eq.) In water was treated with formic acid (the same volume of water) and the reaction mixture was stirred at temperature in the range of from 0 ° C to 50 ° C (preferably room temperature). The pH was adjusted to 8–9 using 1N NaOH and the product was extracted twice with EA. The organic layer was dried over MgSO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC or HPLC provided the desired compound.

General Procedure O: Carbamate Formation (2):

In a glass jar, under an inert atmosphere (N2), to a solution of the appropriate aminotriazole derivative (1.0 eq.) In AcCN (or CH2Cl2) (0.05M solution), 4-nitrophenyl chloroformate (1, 1 eq.) And DIPEA (1.0 eq.). The mixture was stirred for 30 min, and then transferred to glass jars containing the appropriate alcohol (1.4 eq.), Under an inert atmosphere. After adding DIPEA (1.0 eq.), The mixture was stirred at 60 ° C for 12 h. The reaction mixture was poured into a syringe containing diatomaceous earth (Isolute HM-N from Separtis) treated with 1M NaOH (1.25 ml per g of Isolute®). The product was eluted with CH2Cl2 (3 × 1 ml). The solvent was removed under reduced pressure. Purification of the residue by FC or HPLC provided the desired compound.

General Procedure Q: Addition Grignard:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.1M solution of aldehyde (1.0 eq.) In THF was treated at –78 ° C with bromide of cyclopropyl– or appropriate alkyl-magnesium (4.0 eq.). The reaction mixture was stirred at -78 ° C for 90 min and at room temperature for 45 min before being quenched by pouring it into saturated aqueous NH4Cl, extracted with EA and the combined organic extracts dried over MgSO4, filtered, and the solvents They were removed under reduced pressure. Purification of the residue by FC provided the desired compound.

General Procedure Q: Alcohol Oxidation:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.1M solution of alcohol (1.0 eq.) In CH2Cl2 was treated at room temperature with NMO (3.0 eq .) and the reaction mixture was stirred for 5 min. TPAP (0.1 eq.) Was then added and the reaction mixture was stirred for 2 h at room temperature and then the solvent was removed under reduced pressure. Purification of the residue by FC provided the desired compound.

General Procedure R: Condensation:

OR

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), an aldehyde derivative solution (1 eq.) In dichloroacetic acid methyl ester (1.0 eq.) 1.45M suspension of KOt-Bu (1.0 eq.) in THF was added for 1h at -78 ° C. The reaction mixture was stirred at -78 ° C for 5 h and at room temperature overnight. The solvent was removed under reduced pressure and the residue was dissolved in EA and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure to provide the corresponding 3-chloro-2-oxo-propionic acid methyl ester derivative.

General Procedure S: Cycling (4):

S

OR

R1

Cl O O O R R3 NH2 R3 N S R1 O R

R3 represents (C1-C4) alkyl or cyclopropyl. In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.5M solution of the respective thioamide (1.0 eq.) In MeCN was added to a 2.2M solution from 31

respective ester derivative of 3-chloro-2-oxo-propionic acid (1.0 eq.) in MeCN along molecular sieves 4Å (91 mg per mmol of thioamide). After stirring at room temperature for 5 h, the mixture was cooled with an ice bath and the precipitate obtained was filtered. The residue was washed with cold MeCN, dried, dissolved in MeOH

(1.12 times the amount of MeCN that was used for thioamide) and stirred at 50 ° C for 6 h. The solvents were removed under reduced pressure to provide the corresponding thiazole-4-carboxylic acid ester derivative.

General Procedure T: Cycling (5):

S OR R Cl O NH2 N OH2N R H2NR1 O

S

R1 O

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.57M solution of the ester derivative of 3-chloro-2-oxo-propionic acid (1.0 eq. ) in acetone was added to a 0.72M solution of thiourea (1.0 eq.) in acetone. The reaction mixture was stirred overnight at 57 ° C. The cold reaction mixture was filtered and the solvent was removed under reduced pressure. The residue was dissolved in water to obtain a 0.2M solution, which was treated with aq NaHCO3. sat. until pH 7. The mixture was then extracted with ether, the organic layers were combined, dried over MgSO4 and the solvent was removed under reduced pressure to provide the desired 2-amino-thiazole derivative.

General Procedure U: Sandmeyer reaction:

NH2 Br H.H

NN

R1 R1

OO OO RR

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.18M solution of CuBr2 (0.97 eq.) In AcCN was carefully treated with isoamyl nitrite (1.45 eq.) at 5 ° C. The reaction mixture was stirred for 30 min and then the ester derivative of 2-amino-thiazole-4-carboxylic acid ester (0.86 eq.) Was added portionwise. The resulting mixture was stirred at room temperature for 15 min, then at 40 ° C for 30 min and at 65 ° C for 1 h. The solvent was removed under reduced pressure and the residue was purified by FC to provide the desired bromine derivative.

General Procedure V: Dehalogenation:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an atmosphere of H2, a 0.16M solution of bromide (1.0 eq.) In EtOH was reduced with Pd / C (10% Pd , 200 mg for 1 mmol of bromide). The reaction mixture was filtered with Celite and the solvent was removed under reduced pressure to provide desired reduced derivative.

General Procedure W: Esterification:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 1M solution of the acid (1.0 eq) in MeOH was treated at 0 ° C with thionyl chloride (1, 1 eq). The resulting mixture was then stirred at room temperature overnight. The volatiles were removed under reduced pressure and the residue was triturated in EA and filtered to provide the desired compound. Purification of the residue by FC or HPLC provided the desired compound.

General Procedure X: Amide Coupling:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.2M solution of acid (1.0 eq) in CH2Cl2 was treated at 0 ° C with HOBt (1, 1 eq), DCC (1.1 eq) N-methylmorpholine (1.5 eq) and the amide (1 eq). The resulting mixture was stirred at room temperature for 2 h, poured into 5% KHSO4, stirred for 15 min, filtered and washed with CH2Cl2. The aqueous phase was extracted with CH2Cl2 and the combined organic phases were washed with saturated NaHCO3, aqueous brine, dried over MgSO4, filtered and the solvent was removed under reduced pressure. Purification of the residue provided the title compound.

General Procedure Y: Cycling:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 0.13M solution of amide (1 eq) in CH2Cl2 was treated at 0 ° C with Dess – Martin peridionan (1 , 0 eq). The resulting mixture was stirred at room temperature for 1 hour and filtered through a short plug of basic alumina (activity I) and sand in a jar containing a freshly prepared solution of triphenylphosphine (2.02 eq), I2 (2 , 0 eq) and Et3N (4.0 eq) in CH2Cl2 (same amount as in the oxidation stage). The filter cake was washed with CH2Cl2. After 15 minutes, the reaction mixture was transferred to a separatory funnel, treated with. Saturated aqueous Na2S2O3 and extracted with CH2Cl2. The organic layer was washed with saturated aqueous NaHCO3, filtered, and the solvent was removed under reduced pressure. Purification of the residue provided the desired compound.

General Procedure Z: Ester Hydrolysis:

A 0.2M solution of the respective carboxylic acid ester (1.0 eq.) In a mixture of THF and the corresponding alkyl alcohol for example, MeOH or EtOH, was treated with aq. NaOH. 1M (5.0 eq.) And the reaction mixture was stirred at room temperature until completion. The reaction mixture was acidified (pH = 3-4) by the addition of 1M aqueous HCl and the mixture was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and the solvents removed under reduced pressure to provide the desired carboxylic acid derivative after drying.

General Procedure Z1: Amide Coupling:

In a glass flask, under an inert atmosphere (N2), a 0.04M solution of lithium carboxylate (1.0 eq.) In DMF was treated with HATU (1.0 eq) and the reaction mixture was stirred at temperature ambient for 10 min. A 0.07M solution of amine (1.0 eq) in DMF was then added followed by DIPEA (2.84 eq) and the resulting mixture was stirred at room temperature until completion. Water was added and the aqueous layer was extracted twice with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC or HPLC provided the desired compound.

Intermediary Synthesis

5– (4-Nitro– [1,2,3] triazol-2-ylmethyl) -furan-2-carboxylic acid methyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4-nitro-2H– [1,2,3] triazole (1.50 g, 13.15 mmol) in acetone (26.3 ml) was treated with 5-chloromethyl-furan-2-carboxylic acid methyl ester (2.66 g, 14.47 mmol) followed by K2CO3 (9.18 g, 65.75 mmol ) and TBA bromide (848 mg, 2.63 mmol). The reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, water (50 ml) was added and the product was extracted with EA (3 × 30 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) provided the title compound as a yellow oil. TLC: rf (50:50 hept – EA) = 0.22. LC – MS – conditions 02: tR = 0.90 min.

[5– (4 – Nitro– [1,2,3] triazol – 2-ylmethyl) –furan – 2-yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (4-nitro– [1,2,3] triazole-2-ylmethyl acid methyl ester ) –Furan – 2 – carboxilic (325 mg,

1.28 mmol) in THF (13.0 ml) was treated by dripping at -10 ° C with DiBAL (4.36 ml of a solution in toluene, 4.36 mmol). The reaction mixture was stirred at –10 ° C for 1 h followed by 1 h at room temperature. Aqueous Rochelle salt (40 ml) was added and the reaction mixture was stirred for 1 h at room temperature. The aqueous layer was extracted with EA (2 × 30 ml). The combined organic extracts were dried over MgSO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) gave the title compound: TLC: rf (50:50 hept-EA) = 0.28. LC – MS– 02 conditions: tR = 0.77 min.

5– (4 – Nitro– [1,2,3] triazol – 2-ylmethyl) –furan – 2 – carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [5– (4-nitro– [1,2,3] triazole – 2-ylmethyl) –furan -2-yl] -methanol (248 mg, 1.11 mmol) in AcCN (11.0 ml) was treated at room temperature with MnO2 (644 mg, 6.67 mmol). The reaction mixture was stirred at room temperature overnight before being filtered through Celite and the solvent was removed under reduced pressure. Purification of the residue by FC (40:60 hept-EA) provided the title compound: TLC: rf

(40:60 hept – EA) = 0.26. LC – MS 02 conditions: tR = 0.84 min.

1– [5– (4 – Nitro– [1,2,3] triazol – 2-ylmethyl) –furan – 2-yl] –ethanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (4-nitro– [1,2,3] triazole – 2-ylmethyl) –furan– 2-carbaldehyde (180 mg, 0.81 mmol) in CH2Cl2 (8.0 ml) was treated at -10 ° C with trimethylaluminum (0.32 ml of a 2M solution in heptane, 0.64 mmol). The reaction mixture was stirred at 0 ° C for 2 h and then poured into. Saturated aqueous NH4Cl (5 ml) was diluted with CH2Cl2 (10.0 ml) followed by 1N HCl (10 ml). The mixture was extracted with CH2Cl2 (2 × 20 ml). The combined organic extracts were dried over MgSO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) provided the title compound as a yellow oil: TLC: rf (50:50 hept-EA) = 0.31. Conditions LC – MS 02: tR = 0.82 min.

1– [5– (4 – Nitro– [1,2,3] triazol – 2-ylmethyl) –furan – 2 – il] –ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– [5– (4-nitro– [1,2,3] triazole-2-ylmethyl) –Furan – 2-yl] –ethanol (98 mg, 0.41 mmol) in AcCN

(4.0 ml) was treated at room temperature with MnO2 (238 mg, 2.47 mmol) and the reaction mixture was stirred for 2 days at room temperature before being filtered through Celite. The solvent was removed under reduced pressure to provide the title compound as a white solid. Conditions LC – MS– 02: tR = 0.86 min.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and a Dean – Stark under an inert atmosphere (N2), a solution of 1– [5– (4 – nitro– [1,2,3] triazole– 2-ylmethyl) -furan-2-yl] -ethanone (180 mg, 0.76 mmol) in ethylene glycol (0.85 ml, 15.24 mmol) was treated with trimethyl orthoformate (0.17 ml, 1.52 mmol) and tetrafluorborate lithium (14 mg, 0.15 mmol). The resulting mixture was heated at 95 ° C overnight. The reaction mixture was allowed to cool to room temperature. NaHCO3 (10 ml) and EA (10 ml) were added and the aqueous phase was extracted with EA (2 × 10 ml). The combined organic extracts were washed with brine (10 ml), dried over MgSO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC

(60:30 hept – EA) provided the title compound as a colorless oil: TLC: rf (60:30 hept – EA) = 0.31. LC-MS conditions 02: t R = 0.94 min; [M + H] + = 281.01.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [5– (2-methyl– [1,3] ddioxolan – 2 – il) –furan –2 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (218 mg, 0.78 mmol), iron powder (132 mg, 2.33 mmol) and NH4Cl (210 mg, 3.89 mmol) in a mixture of EtOH (4.0 ml) and water (2.0 ml) was stirred at 75 ° C for 0.5 h. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (20 ml) was added followed by 1M NaOH (20 ml). The aqueous layer was extracted with CH2Cl2 (2 × 20 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil. LC-MS conditions 02: t R = 0.71 min; [M + H] + = 251.16.

2 – Furan – 2 – il – 2 – methyl– [1,3] dioxolane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1-furan-2-yl-ethanone (50.00 g, 454.0 mmol) in ethylene glycol (500 , 0 ml) was treated with trimethyl orthoformate (100.0 ml, 908.0 mmol) followed by LiBF4 (7.00 g, 75 mmol). The reaction mixture was heated at 95 ° C overnight. Saturated aqueous NaHCO 3 (500 ml) was added and the mixture was extracted with EA (500 ml). The organic extracts were washed with brine (2 × 250 ml), dried over MgSO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by distillation (11 mbar, 71–73 ° C) proportions the title compound as a colorless oil.

[5– (2 – methyl– [1,3] ddioxolan – 2-il) –furan – 2 – il] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of n-BuLi (14.6 ml of a 1.6M solution in hexane, 23.35 mmol) in THF (21 ml) at -78 ° C was added dropwise a solution of 2-furan-2-yl-2-methyl- [1,3] dioxolane (3.00 g, 19.46 mmol) in THF (6.0 ml). The reaction mixture was then stirred for 1 h at -78 ° C before dropping DMF (4.52 ml, 58.38 mmol). The reaction mixture was stirred for 1 h at –78 ° C. Saturated aqueous NH4Cl (50 ml) was added and the mixture was extracted with EA (2 × 50 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide 5.91 g of the crude 5– (2-methyl– [1,3] ddioxolan-2-yl) -furan-2-carbaldehyde in the form of an orange oil. LC-MS-02 conditions: t R = 0.75 min; [M + H] + = 183.23. The crude technical was dissolved, under an inert atmosphere (N2) in MeOH (59.0 ml) and treated at 0 ° C, in portions, for 20 min, with NaBH4 (1.53 g, 38.92 mmol in five equal portions) . The reaction mixture was stirred for 45 min at room temperature. The reaction mixture was poured into water (80 ml) and the aqueous layer was extracted with EA (2 × 60 ml). The combined organic extracts were dried over MgSO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) provided the title compound: TLC: rf (50:50 hept-EA) = 0.27. LC-MS conditions 02: t R = 0.65 min; [M + H] + = 185.28.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [5– (2-methyl– [1,3] ddioxolan – 2 – il) –furan – 2 -Yl] -methanol (3.20 g, 17.37 mmol) in dry CH2Cl2 (32.0 ml) was treated at 0 ° C with 3N Et (3.14 ml, 22.59 mmol) followed by DMAP (212 mg, 1.74 mmol) and Ms-Cl (1.62 ml, 20.85 mmol). After stirring at room temperature for 2 h, the reaction mixture was quenched with water (30 ml), extracted with CH2Cl2 (30 ml) and the combined organic extracts dried over MgSO4, filtered and the solvents removed under pressure. reduced to provide 4.49 g of crude 2– (5-chloromethyl-furan-2-yl) –2– methyl– [1,3] dioxolane in the form of a brown oil. Crude acetone technician (43 ml) was treated under an inert atmosphere (N2) with 4-nitro-2H– [1,2,3] triazole (1.97 g, 17.27 mmol), K2CO3 (7.16 g , 51.82 mmol) followed by TBA bromide (1.11 g, 3.45 mmol). The reaction mixture was stirred for 2 days at room temperature. Water (30 ml) was added, followed by EA (40 ml). The aqueous layer was extracted with EA (40 ml) and the combined organic extracts were dried over MgSO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (60:40 hept-EA) provided the title compound as an orange oil: TLC: rf (60:40 hept-EA) = 0.28. LC-MS conditions 02: t R = 0.95 min; [M + H] + = 281.01.

2– (5 – Chloromethyl – furan – 2 – yl) –2 – methyl– [1,3] dioxolane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [5– (2-methyl– [1,3] ddioxolan – 2 – il) –furan – 2 -Yl] -methanol (3.50 g, 19.00 mmol) in dry CH2Cl2 (35.0 ml) was treated at 0 ° C with 3N Et (3.44 ml, 22.80 mmol) followed by DMAP (232 mg, 1.90 mmol) and Ms-Cl (1.77 ml, 22.80 mmol). After stirring at room temperature for 2 h, the reaction mixture was quenched with water (40 ml), extracted with CH2Cl2 (40 ml) and the combined organic extracts dried over MgSO4, filtered, and the solvents removed under reduction. Purification of the residue by FC (8: 2: 0.1 hept-EA-Et3N) provided the title compound as a yellow oil: TLC: rf (4: 1 hept-EA) = 0.35.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4-nitro-2H– [1,2,3] triazole (875 mg, 7.67 mmol) in DMF (7.0 ml), it was treated at room temperature with DIPEA (2.63 ml, 15.34 mmol). After 30 min, a solution of 2– (5-chloromethyl-furan– 2-yl) –2-methyl– [1,3] dioxolane (1.87 g, 9.21 mmol) in DMF (7.0 ml) was added ) and the reaction mixture was stirred for 16 h at 50 ° C. Water (100 ml) was added, followed by EA (100 ml). The aqueous layer was extracted with EA (100 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (2: 1 hept-EA) provided the title compound as an orange oil: TLC: rf (2: 1 hept-EA) = 0.26. LC-MS-02 conditions: t R = 0.95 min; [M + H] + = 281.01.

6 – Bromo – hexan – 2 – one:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a commercially available solution of 1-methylcyclopentanol (4.00 g, 39.94 mmol) in CHCl3 (130 ml) at 0 ° C was treated with K 2 CO 3 (33.11 g, 239.62 mmol) and the reaction mixture was stirred for 15 min. Bromide (10.23 ml, 199.68 mmol) was then added and the reaction mixture was stirred at 0 ° C for 2.5 h. The reaction mixture was slowly poured into an ice-cold saturated aqueous Na2S2O3 solution (100 ml). The organic layer was washed with water (2 × 100 ml), dried over MgSO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (gradient hept → 75:25 hept-EA) provided the title compound as a yellow oil: TLC: rf (75:25 hept-EA) = 0.36. 1H NMR (400 MHz, CDCl3) δ 1.66-1.80 (m, 2H), 1.82-1.93 (m, 2H), 2.15 (s, 3H), 2.48 (t, J = 7.3 Hz, 2H), 3.41 (t, J = 6.5 Hz, 2H).

2– (4 – Bromo – butyl) –2 – methyl– [1,3] dioxolane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and a Dean-Stark under an inert atmosphere (N2), a solution of 6-bromine-hexane-2-one (3.34 g, 18.65 mmol ) in toluene (71.3 ml) was treated with ethylene glycol (10.4 ml, 186.92 mmol) and TsOH (35 mg, 0.19 mmol). The reaction mixture was heated at reflux for 3 hours, allowed to cool to room temperature and added. Saturated aqueous NaHCO3 (100 ml) and ether (100 ml) and the aqueous phase was washed with water (2 × 100 ml), dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound. . 1H NMR (400 MHz, CDCl3) δ 1.34 (s, 3H), 1.50-1.65 (m, 2H), 1.65-1.75 (m, 2H), 1.84-1, 98 (m, 2H), 3.43 (t, J = 6.8 Hz, 2H), 3.90-4.04 (m, 4H).

2– [4– (2 – methyl– [1,3] ddioxolan – 2-yl) –butyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4-nitro-2H– [1,2,3] triazole (100 mg, 0.88 mmol) and Cs2CO3 (315 mg, 0.96 mmol) in AcCN (1.0 ml) was treated with a solution of 2– (4-bromo-butyl) –2-methyl– [1,3] dioxolane (215 mg, 0.96 mmol) in AcCN (1.0 ml). The reaction mixture was stirred at 80 ° C for 16 h. Water (20 ml) was added, followed by EA (30 ml). The aqueous layer was extracted with EA (30 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (2: 1 hept-EA) gave the title compound: TLC: rf (2: 1 hept-EA) = 0.33. Conditions LC – MS 02: tR = 0.92 min.

2– [4– (2 – methyl– [1,3] ddioxolan – 2-yl) –butyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [4– (2-methyl– [1,3] ddioxolan – 2 – il) –butyl ] –4 – nitro – 2H– [1,2,3] triazole (250 mg, 0.98 mmol), iron powder (165 mg, 2.93 mmol) and NH4Cl (264 mg, 4.88 mmol) in a mixture of EtOH (3.0 ml) and water (1.5 ml) was stirred at 85 ° C for 30 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (20 ml) was added followed by water (20 ml). The aqueous layer was extracted with CH2Cl2 (2 × 20 ml) and the combined organic extracts were dried over MgSO4, filtered and the solvents were removed under reduced pressure to give the title compound as a pale yellow oil. LC-MS conditions 02: t R = 0.66 min; [M + H] + = 227.47.

[5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiophene – 2 – yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to a solution of commercially available 2-methyl-2-thiophene-2-yl- [1,3] dioxolane (5) .00 g, 28.49 mmol) in THF (145.0 ml) at -78 ° C was added dropwise N, N, N ', N'-tetramethyl-ethylenediamine (4.41 ml, 29.06 mmol) followed by n-BuLi (18.14 ml of a 1.6M solution in hexane, 29.06 mmol), keeping the temperature at –78 ° C. The reaction mixture was then stirred for 2 h at -78 ° C before DMF (6.74 ml, 87.22 mmol) was added dropwise. The cooling bath was removed and the reaction mixture was stirred for 16 h. The reaction mixture was poured into saturated aqueous NaH4Cl (200 ml) and extracted with EA (2 × 200 ml). The combined organic extracts were dried over MgSO4, filtered and the solvent was removed under reduced pressure to provide 5– (2-methyl– [1,3] dioxolan-2-yl) -thiophene-2-carbaldehyde as a yellow oil LC-MS conditions 02: t R = 0.87 min; [M + AcCN] + = 240.32. The crude technical was dissolved under an inert atmosphere (N2) in MeOH (51.2 ml) and treated at 0 ° C, in portions, for 20 min, with NaBH4 (1.35 g, 34.19 mmol in five equal portions ). The reaction mixture was stirred for 45 min at room temperature. The reaction mixture was poured into water (90 ml) and the aqueous layer was extracted with EA (2 × 225 ml). The combined organic extracts were dried over MgSO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) provided the title compound: TLC: rf (50:50 hept-EA) = 0.40. LC-MS conditions 02: t R = 0.73 min; [M + H] + = 201.46.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiophene – 2-ylmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [5– (2-methyl– [1,3] ddioxolan – 2 – il) –tiofen – 2 -Yl] -methanol (2.5 g, 12.48 mmol) in dry CH2Cl2 (25.0 ml) was treated at 0 ° C with Et 3N (2.26 ml, 16.23 mmol) followed by DMAP (152 mg, 1.25 mmol) and Ms-Cl (1.16 ml, 14.98 mmol). The reaction mixture was stirred at room temperature for 2 h before quenching with water (30 ml), extracted with CH2Cl2 (50 ml) and the combined organic extracts dried over MgSO4, filtered, and the solvents removed under pressure. reduced to provide 2.16 g of the crude 2– (5-chloromethyl-thiophene-2-yl) - 2-methyl– [1,3] dioxolane in the form of a yellow oil. A solution of the crude technician 2.11g) in DMF (15 ml) was treated at room temperature with a solution of (4-nitro-2H- [1,2,3] triazole (226 mg, 2.00 mmol) in DMF (15.0 ml) pre-treated for 30 minutes with DIPEA (2.76 ml, 16.13 mmol) The resulting mixture was stirred overnight at 50 ° C. Water (100 ml) was added, followed by EA (100 ml). Combined organic extracts were washed with water (100 ml), dried over MgSO4, filtered and the solvents were removed under reduced pressure Purification of the residue by FC (2: 1 hept-EA) provided the title compound as a white solid: TLC: rf (2: 1 hept-EA) = 0.17. LC-MS conditions 02: tR = 0.98 min; [M + H] + = 297.08.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiophene – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [5– (2-methyl– [1,3] ddioxolan – 2 – il) –tiofen –2 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (1.09 g,

3.68 mmol), iron powder (623 mg, 11.05 mmol) and NH4Cl (995 mg, 18.41 mmol) in a mixture of EtOH (10.0 ml) and water (5.0 ml) was stirred at 85 ° C for 20 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (30 ml) was added followed by 1M NaOH (20 ml). The aqueous layer was extracted with CH2Cl2 (2 × 20 ml) and the combined organic extracts were dried over MgSO4, filtered and the solvents were removed under reduced pressure to give the title compound as a yellow oil. LC-MS conditions 02: t R = 0.78 min; [M + H] + = 267.30.

1– (3 – Bromo – phenyl) –ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a suspension of 1,3-dibromobenzene (2.45 g, 10.07 mmol) in THF (25.0 ml) is treated at -78 ° C with n-BuLi (4.0 ml of a 2.5M solution in hexane, 10.00 mmol). The reaction mixture was stirred for 30 min before adding N, N-dimethylacetamide (1.50 ml, 16.13 mmol) and the solution was then allowed to warm to room temperature for 1 h. Saturated aqueous NH4Cl was then added and the aqueous layer was extracted with Et2O (3 × 50 ml) and the combined organic extracts were dried over Na2SO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (20: 1 hept-EA) provided the title compound as a white solid: TLC: rf (10: 1 hept-EA) = 0.28. LC-MS conditions 02: t R = 0.95 min.

2– (3 – Bromo – phenyl) –2 – methyl– [1,3] dioxolane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– (3-bromo-phenyl) -ethanone (1360 mg, 6.83 mmol) in ethioen glycol (8 .00 ml, 143.46 mmol) was treated with trimethyl orthoformate (1.50 ml, 13.68 mmol) followed by LiBF4 (131 mg, 1.37 mmol). The reaction mixture was heated at 95 ° C for 15 h. It was added. Saturated aqueous Na2CO3 and the mixture was extracted twice with ether and the combined organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (20: 1 hept-EA) provided the title compound as a yellow oil: TLC: rf (10: 1 hept-EA) = 0.34. Conditions LC – MS 02: tR = 1.01 min.

3– (2 – methyl– [1,3] ddioxolan – 2-yl) –benzaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), at a solution of 2– (3-bromo-phenyl) –2 – methyl– [1,3] dioxolane (944 mg, 3.88 mmol) in THF (20.0 ml) at -78 ° C was added dropwise n-BuLi (1.60 ml of a 2.5M solution in hexane, 4.00 mmol). The reaction mixture was then stirred for 30 min at -78 ° C and before DMF (0.40 ml, 5.17 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature for 1 hour. Saturated aqueous NH4Cl was added and the mixture was extracted three times with Et2O. The combined organic extracts were dried over NaSO4, filtered and the solvent was removed under reduced pressure to give the crude title compound as a pale yellow oil. Conditions LC – MS – conditions 02: tR = 0.87 min.

[3– (2 – methyl– [1,3] ddioxolan – 2-yl) –phenyl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to an ice-cold solution of 3– (2 – methyl– [1,3] ddioxolan – 2 – il) - Benzaldehyde (896 mg, 4.66 mmol) in MeOH (10.0 ml) was added NaBH4 (228 mg, 5.79 mmol in four equal portions). The reaction mixture was then stirred for 1 h at room temperature. Water was added and the mixture was extracted twice with EA. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and the solvent was removed under reduced pressure to provide the title compound as a colorless oil: TLC: rf

(50:50 hept – EA) = 0.28. LC-MS conditions 02: t R = 0.74 min; [M + H] + = 195.71.

Ester 3– (2-methyl– [1,3] ddioxolan – 2-yl) –benzethyl of methanesulfonic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [3– (2-methyl– [1,3] ddioxolan – 2-yl) –phenyl] - Methanol (786 mg, 4.05 mmol) in dry CH2Cl2 (10.0 ml) was treated at 0 ° C with Et 3N (0.75 ml, 5.33 mmol) followed by DMAP (49 mg, 0.41 mmol) and Ms-Cl (0.40 ml, 5.15 mmol). After stirring at 0 ° C for 1 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (80:20 to 20:10 hept-EA) provided the title compound as a white solid. Conditions LC – MS 02: tR = 0.91 min.

2– [3– (2 – methyl– [1,3] ddioxolan – 2-yl) –benzyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4-nitro-2H– [1,2,3] triazole (50 mg, 0.43 mmol) in DMF (1.0 ml) it was treated with DIPEA (0.15 ml, 0.87 mmol). After 30 min, a solution of 3– (2-methyl– [1,3] ddioxolan-2-yl) -benzyl ester of methanesulfonic acid (106 mg, 0.52 mmol) in DMF (1.0 mL) was added ) and the reaction mixture was stirred for 3 days at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over Na2SO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (2: 1 hept-EA) provided the title compound as a colorless oil: TLC: rf (1: 2 hept-EA) = 0.42. Conditions LC – MS 02: tR = 0.99 min.

2– [3– (2 – methyl– [1,3] ddioxolan – 2-yl) –benzyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [3– (2-methyl– [1,3] ddioxolan – 2 – il) –benzil ] –4 – nitro – 2H– [1,2,3] triazole (33 mg, 0.11 mmol), iron powder (19 mg, 0.34 mmol) and NH4Cl (31 mg, 0.57 mmol) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 75 ° C for 1 h. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by 1N NaOH (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over Na2SO4, filtered and the solvents removed under reduced pressure to give the title compound as a yellow oil. LC-MS conditions 02: t R = 0.78 min; [M + H] + = 261.13.

6– (4 – Nitro– [1,2,3] triazole – 2 – yl) –hexan – 2 – one:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a suspension of 4-nitro-2H– [1,2,3] triazole (114 mg, 1.00 mmol) in DMF (1.0 ml) was treated with DIPEA

(0.34 ml, 2.00 mmol). After 30 min, a solution of 6-bromo-hexane-2-one (179 mg, 1.00 mmol) in DMF (1.0 ml) was added and the reaction mixture was stirred for 24 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over Na2SO4, filtered and the solvents removed under reduced pressure. Purification of the residue by FC (2: 1 hept-EA) provided the title compound as a yellow oil: TLC: rf (2: 1 hept-EA) = 0.26. Conditions LC – MS 02: tR = 0.86 min.

2– (5,5 – difluor – hexyl) –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 6– (4 – nitro– [1,2,3] triazole – 2 – yl) –hexan– 2-one (118 mg, 0.56 mmol) was dissolved at room temperature in (diethylamino) sulfur trifluoride (0.15 ml, 1.11 mmol) and the reaction mixture was stirred overnight at 50 ° C. The reaction mixture was poured on ice (20 ml) and the mixture was extracted with CH2Cl2 (2 × 20 ml), washed with water (30 ml), brine (30 ml), dried over MgSO4, filtered, and The solvents were removed under reduced pressure. Purification of the residue by FC (4: 1 hept-EA) gave the title compound as a yellow title: TLC: rf (4: 1 hept-EA) = 0.32. Conditions LC – MS 02: tR = 1.01 min.

2– (5.5 – difluor – hexyl) –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– (5,5 – difluor – hex) –4 – nitro – 2H– [1,2, 3] triazole (71 mg, 0.30 mmol), iron powder (51 mg, 0.91 mmol) and NH4Cl (82 mg, 1.52 mmol) in a mixture of EtOH (1.0 ml) and water ( 0.5 ml) was stirred at 85 ° C for 20 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by water (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered and the solvents were removed under reduced pressure to give the title compound as a yellow oil. LC-MS conditions 02: t R = 0.79 min; [M + H] + = 205.54.

5-Methylsulfanyl-furan-2-carboxylic acid ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 5-nitro-furan-2-carboxylic acid ethyl ester solution (5.00 g, 27.01 mmol ) in DMSO (34.5 ml) was treated at room temperature with sodium methantiolate (2.05 g 27.82 mmol). The mixture was then stirred overnight at 100 ° C, treated at room temperature with. Saturated aqueous NH4Cl (250 ml) and the aqueous layer was extracted with EA (3 × 100 ml). The combined organic extracts were washed with saturated aqueous NaHCO3 (100 ml) and brine (100 ml), dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (70:30 hept-EA) provided the title compound: TLC: rf (70:30 hept-EA) = 0.52. LC-MS conditions 02: t R = 0.96 min; [M + AcCN + H] + = 228.23.

5-Methanesulfonyl-furan-2-carboxylic acid ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 5-methylsulfanyl-furan-2-carboxylic acid ethyl ester solution (1.74 g, 9.34 mmol ) in CH2Cl2 (16.0 ml) was carefully treated at room temperature with m-CPBA (3.28 g, 13.32 mmol). The mixture was then stirred for 2 h at room temperature, treated at room temperature with saturated aqueous Na2CO3 and the organic layer was washed with water and brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the reduced title compound in the form of a yellow solid. Conditions LC – MS 02: tR = 0.83 min.

(5 – methanesulfonyl – furan – 2 – yl) –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 5-methanesulfonyl-furan-2-carboxylic acid ethyl ester solution (1.26 g) in THF (57 , 0 ml) was treated at -78 ° C with DiBAL-H (19.50 ml of a 1M solution in THF, 19.50 mmol) and the reaction mixture was stirred at this temperature for 2h. The reaction mixture was poured into Rochelle salt (100 ml) and stirred at room temperature for 12 h. The aqueous layer was extracted with EA (2 × 100 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (30:70 hept-EA) provided the title compound as a yellow oil: TLC: rf (30:70 hept-EA) = 0.28. Conditions LC – MS 02: tR = 0.50 min.

2– (5 – methanesulfonyl – furan – 2 – ylmethyl) –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (5-methanesulfonyl-furan-2-yl) -methanol (692 mg, 3.93 mmol) in Dry CH2Cl2 (7.0 ml) was treated at 0 ° C with Et 3N (0.71 ml, 5.11 mmol) followed by DMAP (50 mg, 0.39 mmol) and Ms-Cl (0.37 ml, 4.71 mmol). After stirring at room temperature for 2 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (20 ml) and the combined organic extracts dried over MgSO4, filtered and the solvents removed under pressure. reduced to provide 868 mg of crude 2-chloromethyl-5-methanesulfonyl-furan in the form of a yellow oil. 183 mg of this crude technical in DMF (0.7 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (90 mg, 0.79 mmol) in DMF (0.7 ml) pre -Treated for 1 h with DIPEA (0.27 ml, 1.59 mmol) and the reaction mixture was stirred for 48 h at room temperature. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (4: 6 hept-EA) provided the title compound as a yellow oil: TLC: rf (4: 6 hept-EA) = 0.36. LC-MS conditions 02: tR = 0.85 min.

2- (5-methanesulfonyl-furan-2-ylmethyl) -2H- [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– (5-methanesulfonyl – furan – 2 – ylmethyl) –4 – nitro – 2H– [1, 2,3] triazole (62 mg, 0.23 mmol), iron powder (39 mg, 0.68 mmol) and NH4Cl (62 mg, 1.14 mmol) in a mixture of EtOH (1.0 ml) and Water (0.5 ml) was stirred at 85 ° C for 30 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by water (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered and the solvents were removed under reduced pressure to give the title compound as a yellow oil. LC-MS conditions 02: t R = 0.63 min; [M + H] + = 243.27.

4 – Bromo – thiazol – 2 – carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a commercially available 2,4-dibromo-thiazole solution (3.50 g, 14.41 mmol) in dry Et2O (120 ml) was treated with n-BuLi (5.9 ml of a 2.5M solution in hexanes, 14.72 mmol) at -78 ° C. The reaction mixture was stirred at this temperature for 30 min. N, N-dimethylformamide (1.35 ml, 14.47 mmol) was then added and the mixture was allowed to warm to room temperature for a period of 1 h. The reaction was quenched by the addition of saturated aqueous NH4Cl (50 ml). The layers were separated and the aqueous layer was extracted with Et2O (3 × 50 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (10: 1 -> 3: 1 hept-EA) provided the title compound as a pale yellow solid. TLC: rf (1: 1 hept – EA) = 0.21. LC – MS Conditions 02: tR = 0.81 min.

(4 – bromo – thiazol – 2 – il) –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 4-bromo-thiazole-2-carbaldehyde (1.68 g, 8.75 mmol) was dissolved in MeOH (10 ml) NaBH4 (428 mg, 10.86 mmol) was added portionwise at 0 ° C and the reaction mixture was stirred at room temperature for 1 h. Water (10 ml) was added and the mixture was extracted with EA (3 x 20 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (6: 1 -> 2: 1 hept-EA) provided the title compound as a pale yellow solid. TLC: rf

(1: 1 hept – EA) = 0.31. Conditions LC – MS 02: tR = 0.62 min [M + H] + = 194.31.

4-Bromo-2– (tert-butyldimethyl-silanyloxymethyl) -thiazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), (4-bromo-thiazol-2-yl) -methanol (1.37 g, 7.06 mmol) was dissolved in CH2Cl2 secp ( 21 ml) Tert-Butyldimethylsilyl chloride (1.17 g, 7.77 mmol) was added at 0 ° C followed by imidazole (985 mg, 14.47 mmol). The reaction mixture was stirred at room temperature for 2 h. 10% aqueous K2CO3 (10 ml) was added, the layers were separated and the aqueous layer was extracted with CH2Cl2 (2 x 20 ml). The combined organic extracts were dried over MgSO4, filtered and the solvent was removed under reduced pressure to provide the title compound as a colorless oil. TLC: rf (1: 1 hept – EA) = 0.80.

1– [2– (tert-butyldimethyl-silanyloxymethyl) -thiazol-4-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to a solution of 4-bromine-2- (tert-butyldimethyl-silanyloxymethyl) -thiazole (1.94 g, 6 , 29 mmol) in dry Et2O (50 ml) n-BuLi (2.76 ml of a 2.5M solution in hexanes, 6.92 mmol) was added at -78 ° C. The reaction mixture was then stirred for 30 min at -78 ° C before N, N-dimethylacetamide (1.17 ml, 12.58 mmol) was dripped. The reaction mixture was allowed to warm to room temperature for a period of 1 h and was stirred at this temperature for 20 min. Saturated aqueous NH4Cl (20 ml) was added, the layers were separated and the aqueous layer was extracted with Et2O (3 × 30 ml). The combined organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (20: 1 -> 5: 1 hept-EA) provided the title compound as a yellow solid. TLC: rf (1: 1 hept – EA) = 0.51. LC-MS conditions 02: t R = 1.11 min; [M + H] + = 272.39.

2– (tert-butyldimethyl-silanyloxymethyl) –4– (2-methyl– [1,3] ddioxolan – 2-yl) -thiazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– [2– (tert-butyldimethyl-silanyloxymethyl) –thiazole – 4 – yl] –ethanone (1 , 77 g, 6.52 mmol) in ethylene glycol (7 ml) was treated with trimethyl orthoformate (1.46 ml, 13.29 mmol) followed by LiBF4 (125 mg, 1.30 mmol). The reaction mixture was heated at 95 ° C for 4 h. Saturated aqueous Na2CO3 (5 ml) was added and the mixture was extracted with Et2O (2 x 20 ml). The organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (20: 1 -> 3: 1 hept-EA) provided the title compound as a brown oil. TLC: rf (1: 1 hept – EA) = 0.56. LC-MS conditions 02: t R = 1.11 min; [M + H] + = 316.36.

[4– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– (tert-butyldimethyl-silanyloxymethyl) –4– (2-methyl– [1,3] dioxolan –2 – il) –thiazole (1.30 g, 4.12 mmol) in dry THF (10 ml) was treated at 0 ° C with TBAF (6.2 ml of a 1M solution in THF, 6.20 mmol) . The reaction mixture was stirred at 0 ° C for 5 min and at room temperature for 1h30. The mixture was then diluted with EA (10 ml), washed with brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue by FC (5: 1 -> 1: 3 hept-EA) provided the title compound as a yellow oil. TLC: rf (1: 2 hept – EA) = 0.20. LC-MS conditions 02: t R = 0.59 min; [M + H] + = 202.48.

2– [4– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [4– (2-methyl– [1,3] ddioxolan – 2 – il) –thiazole – 2 -Yl] -methanol (745 mg, 3.70 mmol) in dry CH2Cl2 (5 ml) was treated at 0 ° C with 3N Et (0.67 ml, 4.79 mmol) followed by DMAP (46 mg, 0.37 mmol) and Ms – Cl (0.37 ml,

4.67 mmol). After stirring at 0 ° C for 1h30, the reaction was quenched with water (5 ml). The organic layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide 1.03 g (quant.) Of methanesulfonic acid ester 4– (2-methyl– [1,3] dioxiolan-2– il) -thiazol-2-ilmethyl crude in the form of a yellow oil. Part of this crude technique (323 mg) in DMF (2.0 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (120 mg, 1.05 mmol) in DMF (2 , 0 ml) pre-treated for 30 min with DIPEA (0.36 ml, 2.10 mmol) and the reaction mixture was stirred for 24 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (1: 2 hept-EA) provided the title compound as a yellow oil: TLC: rf (1: 2 hept-EA) = 0.33. LC-MS 02 conditions: t R = 0.88 min, [M + H] + = 298.16.

2– [4– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole –2 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (145 mg, 0.49 mmol), iron powder (83 mg, 1.46 mmol) and NH4Cl (132 mg, 2, 44 mmol) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 75 ° C for 1 h. The reaction mixture was filtered while heating and the filter cake was rinsed with EtOH. The filtrate was concentrated under reduced pressure and the residue was partitioned between CH2Cl2 (10 ml) and 1M aqueous NaOH (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml). The combined organic extracts were dried over MgSO4, filtered and the solvent was removed under reduced pressure to provide the title compound as a yellow oil (120 mg, 92%). LC-MS conditions 02: t R = 0.68 min, [M + H] + = 268.05.

1– (2 – Bromo – pyridin – 4 – il) –ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under inert atmosphere (N2), a commercially available 2,4-dibromo-pyridine suspension (3.30 g, 13.9 mmol) in dry Et2O (75 ml) it was treated with n-BuLi (5.85 ml of a 2.5M solution in hexanes, 14.6 mmol) at -78 ° C. The reaction mixture was stirred at this temperature for 30 min. N, N-dimethyl-acetamide (2.6 ml, 27.9 mmol) was then added and the mixture was allowed to warm to room temperature for a period of 1 h and stirred at this temperature for 30 min. The reaction was quenched by the addition of saturated aqueous NH4Cl (50 ml). The layers were separated and the aqueous layer was extracted with Et2O (2 × 50 ml). The combined organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (20: 1 to 5: 1 hept-EA) provided the title compound as a white solid. TLC: rf (1: 1 hept – EA) = 0.41. LC-MS-02 conditions: t R = 0.81 min; [M + H] + = 200.61.

2 – Bromo – 4– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 1– (2-bromine-pyridin-4-yl) -ethanone (1650 mg, 8.25 mmol ) in ethylene glycol (8.8 ml) was treated with trimethyl orthoformate (1.85 ml, 16.88 mmol) followed by LiBF4 (158 mg, 1,065 mmol). The reaction mixture was heated at 95 ° C overnight. Saturated aqueous Na 2CO3 (20 ml) was added and the mixture was extracted with Et2O (2 x 30 ml). The organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (6: 1 to 2: 1 hept-EA) provided the title compound as a yellow oil. TLC: rf (1: 1 hept – EA) = 0.57. LC-MS conditions 02: t R = 0.88 min; [M + H] + = 244.19.

4– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2 – carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to a solution of 2-bromine-4- (2-methyl- [1,3] ddioxolan-2-il) -Pyridine (1950 mg, 7.99 mmol) in dry Et2O (40 ml) n-BuLi (3.60 ml of a 2.5M solution in hexanes, 8.79 mmol) was added at -78 ° C. The reaction mixture was then stirred for 30 min at -78 ° C before DMF (0.75 ml, 9.69 mmol) was dripped. The reaction mixture was allowed to warm to room temperature and stirred at this temperature for 10 min. Saturated aqueous NH4Cl (30 ml) was added, the layers were separated and the aqueous layer was extracted with Et2O (3 × 30 ml). The combined organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (10: 1 to 2: 1 hept-EA) provided the title compound as a pale yellow oil. TLC: rf (1: 1 hept – EA) = 0.40.

[4– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2-yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 4– (2-methyl– [1,3] dioxolan-2-yl) -pyridin-2-carbaldehyde (1100 mg, 5.69 mmol) was dissolved in MeOH (15 ml). NaBH4 (278 mg, 7.05 mmol) was added portionwise at 0 ° C and the reaction mixture was stirred at room temperature for 1 h. Water was added and the mixture was extracted with EA (3 x 30 ml). The combined organic extracts were dried over Na2SO4, filtered and the solvents removed under reduced pressure to give the title compound as a yellow oil. LC-MS conditions 02: t R = 0.41 min; [M + H] + = 196.51.

Ester 4– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2-ylmethyl of methanesulfonic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [4– (2-methyl– [1,3] ddioxolan – 2 – il) –pyridin – 2 -Yl] -methanol (950 mg, 4.87 mmol) in dry CH2Cl2 (5 ml) was treated at 0 ° C with Et 3N (0.88 ml, 6.29 mmol) followed by DMAP (60 mg, 0.49 mmol ) and Ms – Cl (0.49 ml,

6.15 mmol). After stirring at room temperature for 2 h, the reaction was quenched with water (5 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (5: 1 to 2: 1 hept-EA) provided the title compound as a yellow oil. Conditions LC – MS 02: tR = 0.76 min, [M + H] + = 274.30.

4– (2-methyl– [1,3] ddioxolan – 2-yl) –2– (4-nitro– [1,2,3] triazol-2-ylmethyl) –pyridine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of methanesulfonic acid ester 4– (2-methyl– [1,3] ddioxolan – 2-yl) - pyridin-2-ylmethyl (315 mg, 1.15 mmol) in DMF (2.0 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (120 mg, 1.05 mmol ) in DMF (2.0 ml) pre-treated for 30 min with DIPEA (0.36 ml, 2.10 mmol) and the reaction mixture was stirred for 48 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (5: 1 to 1: 4 hept-EA) provided the title compound as a pale yellow solid: TLC: rf (1: 2 hept-EA) = 0.24. Conditions LC – MS 02: tR = 0.89 min, [M + H] + = 292.27.

2– [4– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 4– (2-methyl– [1,3] ddioxolan – 2 – il) –2– (4 –Nitro– [1,2,3] triazol-2-ylmethyl) -pyridine (210 mg, 0.71 mmol), iron powder (120 mg, 2.12 mmol) and NH4Cl (191 mg, 3.53 mmol) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 75 ° C for 1 h. The reaction mixture was filtered while heating and the filter cake was rinsed with EtOH. The filtrate was concentrated under reduced pressure and the residue was partitioned between CH2Cl2 (10 ml) and 1M aqueous NaOH (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml). The combined organic extracts were dried over MgSO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (99: 1 to 19: 1 CH2Cl2-MeOH) provided the title compound as a brown oil: TLC: rf

(19: 1 CH2Cl2 – MeOH) = 0.33. LC-MS: t R = 0.64 min, [M + H] + = 262.29.

1– (6 – bromo – pyridin – 2 – il) –ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a suspension of 2,6-dibromopyridine (2.44 g, 10.00 mmol) in ether (25.0 ml) was treated at –78 ° C with n– BuLi (4.0 ml of a 2.5M solution in hexane, 10.00 mmol). The reaction mixture was stirred for 30 min before N, N-dimethylacetamide (1.50 ml, 16.13 mmol) was added and the solution was allowed to warm to room temperature for 1

h. Saturated aqueous NH4Cl was then added and the aqueous layer was extracted with Et2O (2 × 50 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (20: 1 hept-EA) provided the title compound as a white solid: TLC: rf (20: 1 hept-EA) = 0.25. Conditions LC – MS 02: tR = 0.98 min.

2 – Bromo – 6– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– (6-bromine-pyridin-2-yl) -ethanone (1880 mg, 9.40 mmol ) in ethylene glycol (10.00 ml, 179.32 mmol) was treated with trimethyl orthoformate (2.10 ml, 19.16 mmol) followed by LiBF4 (180 mg, 1.88 mmol). The reaction mixture was heated at 95 ° C for 5 h. Saturated aqueous Na2CO3 was added and the mixture was extracted twice with ether and the combined organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (20: 1 hept-EA) provided the title compound as a pale yellow oil: TLC: rf (50:50 hept-EA) = 0.57.

6– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2 – carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to a solution of 2-bromine-6- (2-methyl- [1,3] ddioxolan-2-il) -Pyridine (2.21 g, 9.05 mmol) in Et2O (60.0 ml) at -78 ° C was added dropwise n-BuLi (3.70 ml of a 2.5M solution in hexane, 9.25 mmol) . The reaction mixture was then stirred at -78 ° C for 30 min before DMF (0.85 ml, 11.00 mmol) was added dropwise. The reaction mixture was allowed to warm to room temperature for 1 h. 5% aqueous NaHCO3 was added and the mixture was extracted three times with Et2O. The combined organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (4: 1 hept-EA to pure EA) provided the title compound as a pale yellow solid.

[6– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2-yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to an ice-cold solution of 6– (2 – methyl– [1,3] ddioxolan – 2 – il) - pyridin-2-carbaldehyde (713 mg, 3.69 mmol) in MeOH (10.0 ml) NaBH4 (180 mg, 4.57 mmol in four equal portions) was added. The reaction mixture was then stirred for 1 hour at room temperature. Water was added and the mixture was extracted twice with EA followed by EA-MeOH 9: 1. The combined organic extracts were dried over Na2SO4, filtered and the solvent was removed under reduced pressure to give the title compound as a pale yellow solid. LC-MS conditions 02: t R = 0.46 min; [M + H] + = 196.49.

Ester 6– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2-ylmethyl of methanesulfonic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [6– (2-methyl– [1,3] ddioxolan – 2 – il) –pyridin – 2 -Yl] -methanol (729 mg, 3.74 mmol) in dry CH2Cl2 (10.0 ml) was treated at 0 ° C with 3N Et (0.67 ml, 4.83 mmol) followed by DMAP (46 mg, 0, 37 mmol) and Ms-Cl (0.37 ml, 4.72 mmol). After stirring at 0 ° C for 1 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered, and the solvents removed. under reduced pressure. Purification of the residue by FC (70:30 to 50:50 hept-EA) provided the title compound as a pale yellow oil. LC-MS conditions 02: t R = 0.79 min; [M + H] + = 274.39.

2– (2-methyl– [1,3] ddioxolan – 2-yl) –6– (4-nitro– [1,2,3] triazol-2-ylmethyl) –pyridine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of methanesulfonic acid ester 6– (2-methyl– [1,3] ddioxolan – 2-yl) - pyridin-2-ylmethyl (164 mg, 0.6 mmol) in DMF (2.0 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (57 mg, 0.5 mmol ) in DMF (1.0 ml) pre-treated for 30 min with DIPEA (0.20 ml, 1.17 mmol) and the reaction mixture was stirred for 48 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (4: 1 to 1: 1 hept-EA) provided the title compound as a pale yellow oil: TLC: rf (1: 1 hept-EA) = 0.50. LC – MS 02 conditions: t R = 0.90 min, [M + H] + = 292.35.

2– [6– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– (2-methyl– [1,3] ddioxolan – 2 – il) –6– (4 –Nitro– [1,2,3] triazol-2-ylmethyl) -pyridine (66 mg, 0.23 mmol), iron powder (38 mg, 0.68 mmol) and NH4Cl (61 mg, 1.13 mmol ) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 75 ° C for 1 h. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (20 ml) was added followed by 1N NaOH (20 ml). The aqueous layer was extracted with CH2Cl2 (2 × 20 ml) and the combined organic extracts were dried over MgSO4, filtered and the solvents removed under reduced pressure to give the title compound as a pale green oil: TLC : rf (EA) = 0.50. LC-MS conditions 02: t R = 0.67 min; [M + H] + = 262.40.

2– [6– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– (2-methyl– [1,3] ddioxolan – 2 – il) –6– (4 –Nitro– [1,2,3] triazol-2-ylmethyl) -pyridine (66 mg, 0.23 mmol), iron powder (38 mg, 0.68 mmol) and NH4Cl (61 mg, 1.13 mmol ) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 75 ° C for 1 h. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (20 ml) was added followed by 1N NaOH (20 ml). The aqueous layer was extracted with CH2Cl2 (2 × 20 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a pale green oil. : TLC: rf (EA) = 0.50, LC-MS conditions - 02: tR = 0.67 min; [M + H] + = 262.40,

3– (2 – Hydroxy – ethyl) –benzoic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to a solution of 3-phenethyl bromine alcohol (2.34 g, 11.29 mmol) and N, N, N ', N'-tetramethyl ethylenediamine (3.24 ml, 22.58 mmol) in Et2O (29.0 ml) at -78 ° C, n-BuLi (14.0 ml of a 1.6M solution was added dropwise hexane, 22.59 mmol), keeping the temperature at –78 ° C. The reaction mixture was then stirred at -20 ° C for 2 h. Then dry carbon dioxide gas was allowed to bubble for 10 min through the reaction mixture at -78 ° C. The cooling bath was removed and the reaction mixture was stirred for 1 h. The reaction mixture was extracted with water (50 ml). The aqueous layer was acidified to pH = 1 with 2N HCl and extracted with EA (2 × 75 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a beige solid: LC-MS conditions.

02: t R = 0.67 min.

5– [3– (2-Methoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid methyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– [3– (2-hydroxy-ethyl) –phenyl] –oxazole-4-carboxylic acid ( 100 mg, 0.43 mmol) in DMF (1.0 ml was treated at 0 ° C with NaH (56 mg, 1.29 mmol) and the resulting mixture was stirred for 45 min at 0 ° C. Then iodide was added of methyl (0.14 ml, 2.14 mmol) and the reaction mixture was stirred at room temperature for 45 min. The reaction mixture was quenched with saturated aqueous NH4Cl (20 ml), extracted with EA (2 × 20ml ) and the combined organic extracts were washed with water (2 × 20 ml) dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound. LC-MS– Conditions

02: t R = 0.92 min; [M + H] + = 262.38.

5– (3-tert-Butoxycarbonylphenyl) -oxazol-4-carboxylic acid methyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a suspension of isophthalic acid tert-butyl ester (4.00 g, 18.00 mmol) and carbonate sesquidrate Potassium (6.03 g, 43.20 mmol) in DMF (36.0 ml) was treated with a solution of methyl isocyanoacetate (3.45 ml, 36.00 mmol) in DMF (6.0 ml). After 5 min, the reaction mixture was cooled to 0 ° C and a solution of DPPA (4.01 ml, 18.00 mmol) in DMF (6 ml) was added dropwise. The resulting mixture was stirred at 0 ° C for 2 h and then overnight at room temperature. A 1: 1 mixture of toluene EA (400 ml) was added and the organic layer was washed with water (150 ml), 10% aqueous citric acid solution (150 ml) and saturated aqueous NaHCO3 (150 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (60:40 hept-EA) provided the title compound as a white solid. TLC: rf (60:40 hept – EA) = 0.27. LC-MS 02 conditions: t R = 1.04 min, [M + H] + = 304.32.

5– (3-carboxy-phenyl) -oxazol-4-carboxylic acid methyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (3-tert-butoxycarbonyl phenyl) -oxazole-4-carboxylic acid methyl ester (1 .00 g, 3.30 mmol) in TFA (13.3 ml) was stirred at room temperature for 45 min. TFA was removed under reduced pressure and the residue was triturated in Et2O, filtered and washed with Et2O to give the title compound as a white powder. LC – MS 02 conditions: tR = 0.79 min, [M + H] + = 248.20,

5– (3-Hydroxymethyl-phenyl) -oxazol-4-carboxylic acid methyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a 5– (3-carboxy-phenyl) -oxazole-4-carboxylic acid methyl ester suspension (500 mg, 2.02 mmol) in THF (14.0 ml) at 0 ° C was treated dropwise with BH 3 (10.1 ml of a 1M solution in THF, 10.11 mmol). The resulting mixture was stirred at 0 ° C for 4 h. Then MeOH (14 ml) was dripped. After 30 min, the solvent was removed under reduced pressure. EA (20 ml) was added and the organic phase was washed with 1N NaOH (10 ml), water (10 ml) and brine (10 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (93: 7 CH2Cl2-MeOH) provided the title compound as a white solid. TLC: rf (93: 7 CH2Cl2-MeOH) = 0.32. LC – MS 02 conditions: t R = 0.76 min, [M + H] + = 234.39.

5– (3-Hydroxymethyl-phenyl) -oxazol-4-carboxylic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (3-hydroxymethyl-phenyl) -oxazole-4-carboxylic acid methyl ester (265 mg, 1.13 mmol) in THF (11.0 ml) was treated with 1N NaOH (5.5 ml). The resulting mixture was stirred for 1.5 h, then acidified with 1N HCl, extracted twice with EA (2 x 25 ml) and then the combined organic phases were washed with brine (10 ml). The organic layer was dried over MgSO4, filtered and the solvent was removed under reduced pressure to provide the title compound as a white solid. Conditions LC – MS 02: tR = 0.67 min, [M + AcCN + H] + = 261.29.

5– (3-Methoxymethyl-phenyl) -oxazol-4-carboxylic acid methyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (3-hydroxymethyl-phenyl) -oxazole-4-carboxylic acid (100 mg, 0.43 mmol) at 0 ° C in D MF (1.0 ml) was treated with NaH (56 mg, 1.29 mmol) and the resulting mixture was stirred at 0 ° C for 45 min. MeI (0.14 ml, 2.14 mmol) was added and the reaction mixture was stirred at room temperature for 1.5 h. Saturated aqueous NH4Cl (20 ml) was added and the aqueous layer was extracted with EA (2 x 20 ml). The combined organic layers were washed with water (2 x 10 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give the title compound as a yellow oil. LC-MS conditions 02: t R = 0.89 min, [M + H] + = 248.36.

5– (3-Methoxymethyl-phenyl) -oxazol-4-carboxylic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (3-methoxymethyl-phenyl) -oxazole-4-carboxylic acid methyl ester (280 mg, 1.13 mmol) in THF (11.0 ml) was treated with 1N NaOH (5.5 ml). The resulting mixture was stirred for 1.5 h and then acidified with 1N HCl, extracted twice with EA (2 x 20 ml) and the combined organic phases washed with brine (20 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a white oil. Conditions LC – MS 02: tR = 0.77 min, [M + AcCN + H] + = 275.35.

Amino acid thioxo-acetic acid ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a commercially obtainable oxalamic acid ethyl ester solution (43.429 g, 370.86 mmol) and Lawesson reagent (150, 00 g, 370.86 mmol) in toluene (550.0 ml) was stirred at 80 ° C for 2 h. The resulting mixture was cooled to room temperature and CH2Cl2 (300 ml) was added. The mixture was filtered and the solvents were removed under reduced pressure. Purification of the residue by FC (CH2Cl2) provided the title compound as an orange solid.

4-Chloromethyl-thiazole-2-carboxylic acid ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of amino-thioxoacetic acid ethyl ester (2.50 g, 18.77 mmol) and 1, 3-dichloro-propan– 2-one (2.88 g, 21.59 mmol) in toluene (20.0 ml) was stirred for 2 h at reflux. EtOAc (20 ml) was added at room temperature and the mixture was washed with saturated aqueous NaHCO3 (10 ml) followed by brine (20 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (4: 1 hept-EA) gave the title compound as a light yellow compound. TLC: rf (4: 1 hept – EA) = 0.26. LC – MS 02 conditions: tR = 0.89 min, [M + H] + = 206.40,

(4-chloromethyl-thiazol-2-yl) -methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of ethyl ester of 4-chloromethyl-thiazole-2-carboxylic acid (2.47 g, 12.03 mmol ) in THF (120.0 ml) was treated at -78 ° C with DiBAL (36.09 ml of a 1M solution in THF, 36.09 mmol) and the reaction mixture was stirred for 1 h at -78 ° C and then it was heated for 1 h. The reaction mixture was poured onto a saturated aqueous solution of Rochelle salt and stirred for 1 h at room temperature. The aqueous layer was extracted with EtOAc (2 x 150 ml) and the combined organic layer was washed with brine (200 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC

(1: 1 hept-EA) provided the title compound as a light yellow oil. TLC: rf (1: 1 hept– EA) = 0.30, LC-MS Conditions 02: tR = 0.59 min, [M + H] + = 164.07.

4-chloromethyl-thiazole-2-carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (4-chloromethyl-thiazol-2-yl) -methanol (1.60 g, 9.80 mmol ) in AcCN (98.0 ml) was treated at room temperature with MnO2 (4.73 g, 49.01 mmol). The reaction mixture was stirred at room temperature overnight before being filtered through Celite and the solvent was removed under reduced pressure. Purification of the residue with FC (4: 1 hept-EA) provided the title compound as a colorless oil. TLC: rf (4: 1 hept – EA) = 0.37. Conditions LC – MS 02: tR = 0.77 min.

1– (4 – chloromethyl – thiazol – 2 – yl) –ethanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4-chloromethyl-thiazole-2-carbaldehyde (1.05 g, 6.49 mmol) in CH2Cl2 ( 65.0 ml) was treated at 0 ° C with trimethyl aluminum (32.45 ml of a 1M solution in heptane, 32.45 mmol). The reaction mixture was then stirred ° C for 45 min. Then CH 2 Cl 2 (100.0 ml) was added followed by saturated aqueous NH 4 Cl (80 ml). The mixture was then treated with 1N HCl (100 ml) and the aqueous layer was extracted with CH2Cl2 (100 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil. LC – MS 02 conditions: t R = 0.66 min, [M + H] + = 178.50,

1– (4 – chloromethyl – thiazol – 2 – yl) –ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– (4-chloromethyl-thiazol-2-yl) –ethanol (1.09 g, 6, 15 mmol) in AcCN (61.0 ml) was treated at room temperature with MnO2 (2.97 g, 30.76 mmol) and the reaction mixture was stirred for 16 h at room temperature before being filtered through Celite. The solvent was removed under reduced pressure to provide the title compound as a yellow oil. LC-MS 02 conditions: t R = 0.84 min, [M + H] + = 176.41.

4 – chloromethyl – 2– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazole:

In a flame-dried round bottom flask equipped with a magnetic stir bar and a Dean-Stark apparatus, under an inert atmosphere (N2), a solution of 1– (4-chloromethyl-thiazol-2-yl) -ethanone (992 mg, 5.65 mmol) in ethylene glycol (6.30 ml, 112.96 mmol) was treated with trimethyl orthoformate (1.24 ml, 11.30 mmol) followed by LiBF4 (106 mg, 1.13 mmol). The reaction mixture was heated at 95 ° C for 2 h. NaHCO 3 (50 ml) was added and the mixture was extracted with EA (50 ml). The organic extracts were washed with brine (2 × 50 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (4: 1 hept-EA) provided the title compound as a yellow oil: TLC: rf (4: 1 hept-EA) = 0.30, LC-MS 02 Conditions: tR = 0.84 min, [M + H] + = 220.36.

2– [2– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 4-ylmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4-chloromethyl – 2– (2 – methyl– [1,3] ddioxolan – 2 – il) - thiazole (231 mg, 1.05 mmol) in DMF (1.5 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (100 mg, 0.88 mmol) in DMF ( 1.5 ml) pre-treated for 30 min. with DIPEA (0.30 ml, 1.75 mmol) and the reaction mixture was stirred for 48 h at 50 ° C. Ag ua (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (6: 4 hept-EA) provided the title compound as a pale yellow oil .: TLC: rf (6: 4 hept-EA) = 0.33. LC-MS 02 conditions: t R = 0.90 min, [M + H] + = 298.23.

2– [2– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 4-ylmethyl] –2H– [1,2,3] triazole – 4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole –4 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (86 mg, 0.29 mmol), iron powder (49 mg, 0.87 mmol) and NH4Cl (78 mg, 1, 45 mmol) in a mixture of EtOH (1.0 ml) and water (0.5 ml) was stirred at 75 ° C for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by 1N NaOH, ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as an oil. LC-MS-02 conditions: t R = 0.68 min; [M + H] + = 268.25.

2-Bromo-Pyridine-4-Carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a suspension of 2,4-dibromo-pyridine (1.90 g, 8.02 mmol) in dry Et2O (40 ml) was treated with n-BuLi (3.36 ml of a 2.5M solution in hexanes, 8.42 mmol) at -78 ° C. The reaction mixture was stirred at room temperature for 30 min. Then N, N-dimethylformamide (0.78 ml, 10.03 mmol) was added and the mixture was allowed to warm to room temperature for a period of 1 h and stirred at this temperature for 20 min. The reaction was quenched by the addition of saturated aqueous NH4Cl (30 ml). The layers were separated and the aqueous layer was extracted with Et2O (3 × 50 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (10: 1 to 2: 1 hept-EA) provided the title compound as a white solid. TLC: rf (1: 1 hept – EA) = 0.44.

(2 – Bromo – pyridin – 4 – il) –methanol

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under inert atmosphere (N2), 2-bromo-pyridine-4-carbaldehyde (904 mg, 4.86 mmol) was dissolved in MeOH (10 ml) . NaBH4 (236 mg, 5.99 mmol) was added portionwise at 0 ° C and the reaction mixture was stirred at room temperature for 1 h. Water (10 ml) was added and the mixture was extracted with EA (3 x 20 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a white solid. TLC: rf (1: 1 hept – EA) = 0.22. LC-MS conditions 02: t R = 0.63 min; [M + H] + = 188.33.

2-Bromo-4– (tert-butyl-dimethyl-silanyloxymethyl) -pyridine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), it was dissolved (2-bromo-pyridin-4-yl) -methanol (780 mg, 4.15 mmol) in CH2Cl2 dry (21 ml). Tert-butyl dimethylsilyl chloride (688 mg, 4.56 mmol) was added at 0 ° C, followed by imidazole (579 mg, 8.50 mmol). The reaction mixture was stirred at room temperature for 2 h. 10% aqueous K2CO3 (10 ml) was added, the layers were separated and the aqueous layer was extracted with CH2Cl2 (2 x 20 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a colorless oil. TLC: rf (1: 1 hept-EA) = 0.80, LC-MS Conditions 02: tR = 1.17 min; [M + H] + = 302.29.

1– [4– (tert-butyl-dimethyl-silanyloxymethyl) -pyridin-2-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), to a solution of 2-bromine-4- (tert-butyl-dimethyl-silanyloxymethyl) -pyridine (1.04 g , 3.44 mmol) in dry Et2O (50 ml) n-BuLi (1.60 ml of a 2.5M solution in hexanes, 3.96 mmol) was added at -78 ° C. The reaction mixture was then stirred for 1 h at -78 ° C before dropping N, N-dimethyl acetamide (0.64 ml, 6.88 mmol). The reaction mixture was allowed to warm to room temperature and stirred at this temperature for 10 min. Saturated aqueous NH4Cl (20 ml) was added, the layers were separated and the layer was extracted with Et2O (3 × 30 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (20: 1 to 5: 1 of hept-EA) provided the title compound as a pale yellow oil. TLC: rf (1: 2 hept – EA) = 0.64. LC-MS conditions 02: t R = 1.12 min; [M + H] + = 265.84.

4– (tert-butyl-dimethyl-silanyloxymethyl) -2- (2-methyl– [1,3] dioxolan-2-yl) -pyridine:

In a flame-dried round bottom flask equipped with a magnetic stir bar and a Dean-Stark apparatus under an inert atmosphere (N2), a solution of 1– [4– (tert-butyl-dimethyl-silanyloxymethyl) –pyridin – 2– il] -ethanone (1.78 g, 6.71 mmol) in ethylene glycol (7.14 ml, 127.95 mmol) was treated with trimethyl orthoformate (1.50 ml, 13.67 mmol) followed by LiBF4 ( 128 mg, 1.34 mmol). The reaction mixture was heated at 95 ° C overnight. Saturated aqueous NaHCO3 (50 ml) was added and the mixture was extracted with EA (50 ml). The organic extracts were washed with brine (2 × 50 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (20: 1 to 1: 1 hept-EA) provided the title compound as a pale yellow oil. TLC: rf (1: 1 hept – EA) = 0.50, Conditions LC – MS 02: tR = 0.91 min, [M + H] + = 310.40.

[2– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 4-yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4– (tert-butyl-dimethyl-silanyloxymethyl) –2– (2-methyl– [1,3 ] ddioxolan-2-yl) -pyridine (840 mg, 2.71 mmol) in dry THF (15 ml), was treated at 0 ° C with TBAF (4.70 ml of a 1M solution in THF, 4.70 mmol). The reaction mixture was stirred at 0 ° C for 5 min and at room temperature for 1.5 h. The mixture was then diluted with EA (10 ml), washed with brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (5: 1 to 1: 3 hept-EA) provided the title compound as a yellow oil TLC: rf (1: 2 hept-EA) = 0.10, LC-MS 02 Conditions : t R = 0.33 min; [M + H] + = 196.54.

2– (2-methyl– [1,3] ddioxolan – 2-yl) –pyridin-4-yl methyl ester of methanesulfonic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [2– (2-methyl– [1,3] ddioxolan – 2 – il) –pyridin – 4 –Il] –methanol (530 mg, 2.72 mmol) in dry CH2Cl2 (5 ml) was treated at 0 ° C with Et 3N (0.50 ml, 3.56 mmol) followed by DMAP (34 mg, 0, 27 mmol) and Ms-Cl (0.27 ml, 3.46 mmol). After stirring at room temperature for 2 h, the reaction was quenched with water (5 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (5: 1 to 2: 1 hept-EA) provided the title compound as a light brown oil. TLC: rf (1: 2 hept – EA) = 0.36.

2– (2-methyl– [1,3] ddioxolan – 2-yl) –4– (4-nitro– [1,2,3] triazol-2-ylmethyl) -pyridine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), an ester solution 2– (2-methyl– [1,3] ddioxolan – 2 – il) –pyridin – 4 -Methylsulfonic acid methylmethyl (303 mg, 1.11 mmol) in DMF (2.0 ml) was added to a solution of 4-nitro-2H - [1,2,3] triazole (115 mg, 1.01 mmol ) in DMF (2.0 ml) pre-treated for 30 min with DIPEA (0.35 ml, 2.02 mmol) and the reaction mixture was stirred for 48 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (5: 1 to 2: 1 hept – EA) provided the title compound as a pale yellow oil: TLC: rf (1: 2 hept – EA) = 0.20, LC Conditions– MS 02: t R = 0.77 min, [M + H] + = 292.24.

2– [2– (2 – methyl– [1,3] ddioxolan – 2-yl) –pyridin – 4-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– (2-methyl– [1,3] ddioxolan – 2 – il) –4– (4 –Nitro– [1,2,3] triazol-2-ylmethyl) -pyridine (145 mg, 0.50 mmol), iron powder (84 mg, 1.49 mmol) and NH4Cl (134 mg, 2.49 mmol ) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 75 ° C for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by 1N NaOH, (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a light yellow oil. LC-MS conditions 02: t R = 0.54 min; [M + H] + = 261.78.

2– (4 – bromo – thiophene – 2 – yl) –2 – methyl– [1,3] dioxolane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– (4 – bromine – 2 – thienyl) ethan – 1 – one (2.00 g, 9 , 75 mmol) in ethylene glycol (10.7 ml) was treated with trimethyl orthoformate (2.14 ml, 19.51 mmol) followed by LiBF4 (150 mg, 1.60 mmol). The reaction mixture was heated at 95 ° C overnight. Saturated aqueous NaHCO 3 (20 ml) was added and the mixture was extracted with EA (20 ml). The organic extracts were washed with brine (2 × 20 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (20:80 EA-Hept) provided the title compound as a white solid. TLC: rf (20:80 EA – Hept) = 0.50, Conditions LC – MS 02: tR = 0.99 min.

[5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiophene – 3-yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), at a solution of 2– (4 – bromo – thiophene – 2 – il) –2 – methyl– [1,3 ] dioxolane (1.00 g, 4.01 mmol) in Et2O (36.0 ml) at –78 ° C was added dropwise n-BuLi (2.5 ml of a 1.6M solution in hexane, 4.00 mmol) for 15 min. The reaction mixture was then stirred at -78 ° C for 15 min before dropping DMF (3.1 ml, 40.14 mmol). The cooling bath was removed and the reaction mixture was stirred for 10 min. Saturated aqueous NaH4Cl (40 ml) was added and the aqueous layer was extracted with EA (2 × 100 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide 5– (2-methyl– [1,3] dioxolan-2-yl) -thiophene-3-carbaldehyde as a A yellow oil. Conditions LC – MS 02: tR = 0.84 min. The crude technical was dissolved under an inert atmosphere (N2) in MeOH (9.98 ml) and treated at 0 ° C, in portions, with NaBH4 (284 mg, 7.21 mmol). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was poured into water (16 ml) and the aqueous layer was extracted with EA (2 × 100 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (50:50 hept-EA) provided the title compound as a yellow solid. TLC: rf (50:50 EA – Hept) = 0.21. LC-MS conditions 02: t R = 0.71 min; [M + H] + = 201.49.

2– (4 – chloromethyl – thiophene – 2 – yl) –2 – methyl– [1,3] dioxolane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [5– (2-methyl– [1,3] ddioxolan – 2 – il) –tiofen – 3 –Il] –methanol (460 mg, 2.30 mmol) in dry CH2Cl2 (4.6 ml) was treated at 0 ° C with Et 3N (0.42 ml, 2.99 mmol) followed by DMAP (28 mg, 0.23 mmol) and Ms-Cl (0.21 ml, 2.76 mmol). After stirring at room temperature for 2 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (20 ml) and the combined organic extracts dried over NaSO4, filtered, and the solvents removed under reduced pressure Purification of the residue with FC (4: 1 hept-EA) provided the title compound as a yellow compound. TLC: rf (1: 4 EA – Hept) = 0.35.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiophene – 3-ylmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– (4-chloromethyl-thiophene-2-yl) –2 – methyl– [1,3] dioxolane (230 mg, 1.05 mmol) in DMF (1.5 ml) was added to a solution of 4-nitro-2H- [1,2,3] triazole (100 mg, 0.88 mmol) in DMF ( 1.5 ml) pre-treated for 30 min with DIPEA (0.30 ml, 1.75 mmol) and the reaction mixture was stirred for 16 h at 50 ° C. Agu was added to (10 ml), followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (2: 1 hept-EA) provided the title compound as a pale yellow oil: TLC: rf (2: 1 hept-EA) = 0.47. Conditions LC – MS 02: tR = 0.98 min.

2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-3-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [5– (2-methyl– [1,3] ddioxolan – 2 – il) –tiofen –3 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (50 mg, 0.17 mmol), iron powder (29 mg, 0.51 mmol) and NH4Cl (46 mg, 0, 84 mmol) in a mixture of EtOH (1.0 ml) and water (0.5 ml) was stirred at 85 ° C for 15 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by 1N NaOH (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a pale yellow oil. LC-MS conditions 02: t R = 0.78 min; [M + H] + = 267.28.

5– (tert-Butyl-dimethyl-silanioxymethyl) -isoxazole-3-carboxylic acid ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), commercially obtainable 5-hydroxymethyl-isoxazol-3-carboxylic acid ethyl ester (5.00 g, 26.29 mmol) It was dissolved in dry THF (200 ml). Ter-Butyldimethylsilyl chloride (4.04 g, 26.82 mmol) was added at room temperature followed by imidazole (1.97 g, 28.92 mmol). The reaction mixture was stirred at room temperature overnight. Saturated aqueous NH4Cl (150 ml) was added followed by EA (100 ml) and the layers were separated. The aqueous layer was extracted with EA (2 x 100 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (9: 1 hept-EA) provided the title compound as a pale yellow solid .: TLC: rf (9: 1 hept-EA) = 0.37. LC-MS conditions 02: t R = 1.14 min; [M + AcCN + H] + = 327.51.

[5– (tert-butyl-dimethyl-silanyloxymethyl) -isoxazol-3-yl] -methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (tert-butyl-dimethyl-silanyloxymethyl) -isoxazole-3-carboxylic acid ethyl ester (5 , 77 g, 20.22 mmol) in THF (200 ml) was treated at -78 ° C with IDAL-H (40.00 ml of a 1M solution in THF, 40.43 mmol). The reaction mixture was stirred at this temperature for 1 h before allowing it to warm to room temperature. The reaction mixture was poured onto Rochelle salt (200 ml) and stirred at room temperature for 1 h. The aqueous layer was extracted with EA (2 × 200 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (70:30 hept-EA) gave the title compound as a yellow oil: TLC: rf (70:30 hept-EA) = 0.28. LC-MS conditions 02: t R = 0.99 min; [M + H] + = 244.35.

5– (tert-butyl-dimethyl-silanyloxymethyl) -isoxazol-3-carbaldehyde:

In a round bottom flask, flame dried, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [5– (tert-butyl-dimethyl-silanyloxymethyl) –isoxazol-3-yl] -methanol ( 2.94 g, 12.08 mmol) in AcCN (120.0 ml) was treated at room temperature with MnO2 (8.17 g, 84.56 mmol) and the reaction mixture was stirred for 24 h at room temperature before Filter it through Celite. The solvent was removed under reduced pressure to provide the title compound as a yellow oil: TLC: rf (9: 1 hept-EA) = 0.32. Conditions LC – MS 02: tR = 0.92 min.

1– [5– (tert-butyl-dimethyl-silanyloxymethyl) -isoxazol-3-yl] -ethanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (tert-butyl-dimethyl-silanyloxymethyl) -isoxazole-3-carbaldehyde (1.74 g, 7.22 mmol) in CH2Cl2 (72.0 ml) was treated at 0 ° C with trimethylaluminum (22.0 ml of a 1M solution in heptane, 22.0 mmol). The reaction mixture was then stirred at 0 ° C for 50 min. Then CH2Cl2 (80.0 ml) was added followed by. Saturated aqueous NH4Cl (80 ml). The mixture was then treated with 1N HCl (50 ml) and the aqueous layer was extracted with CH2Cl2 (100 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a colorless oil: TLC: rf (7: 3 hept-EA) = 0.32. LC-MS-02 conditions: tR = 1.01 min, [M + H] + = 258.41.

1– [5– (tert-butyl-dimethyl-silanyloxymethyl) -isoxazol-3-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– [5– (tert-butyl-dimethyl-silanyloxymethyl) –isoxazol – 3-yl] –ethanol (1.79 g, 6.95 mmol) in AcCN (70.0 ml) was treated at room temperature with MnO2 (3.36 g, 34.77 mmol) and the reaction mixture was stirred for 72 h at room temperature before of filtering it through Celite. The solvent was removed under reduced pressure, to provide the title compound as a yellow oil. Conditions LC – MS 02: tR = 1.13 min.

1– (5-hydroxymethyl-isoxazol-3-yl) -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– [5– (tert-butyl-dimethyl-silanyloxymethyl) –isoxazol-3-yl] -ethanone (1.99 g, 7.79 mmol) in ethylene glycol (8.69 ml) was treated with trimethyl orthoformate (1.71 ml, 15.58 mmol) followed by LiBF4 (146 mg, 1.56 mmol). The reaction mixture was heated at 95 ° C overnight. Saturated aqueous NaHCO3 (50 ml) was added and the mixture was extracted with EA (2 × 50 ml). The combined organic extracts were washed with brine (2 × 50 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (40:60 EA-Hept) provided the title compound as a yellow oil. TLC: rf (40:60 EA – Hept) = 0.25. Conditions LC – MS 02: tR = 0.54 min.

1– [5– (4-nitro– [1,2,3] triazol-2-ylmethyl) -isoxazol-3-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– (5-hydroxymethyl-isoxazol-3-yl) -ethanone (262 mg, 1.86 mmol ) in dry CH2Cl2, (2.6 ml) was treated at 0 ° C with Et 3N (0.34 ml, 2.41 mmol) followed by DMAP (23 mg, 0.19 mmol) and Ms-Cl (0, 17 ml, 2.23 mmol). After stirring at room temperature for 2 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts dried over NaSO4, filtered, and the solvents were removed under reduced pressure to provide 1– (5-chloromethyl-isoxazol-3-yl) -ethanone crude as a pale yellow oil. In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of this 1– (5-chloromethyl-isoxazol-3-yl) –ethanone raw in DMF (3.0 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (210 mg, 1.84 mmol) in DMF (3.0 ml) pretreated for 30 min with DIPEA (0, 63 ml, 3.68 mmol) and the reaction mixture was stirred for 16 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (2: 1 hept-EA) provided the title compound as a yellow oil: TLC: rf (2: 1 hept-EA) = 0.26. Conditions LC – MS 02: tR = 0.90 min.

2– [3– (2 – methyl– [1,3] ddioxolan – 2-yl) –isoxazol – 5-ylmethyl] –4-nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– [5– (4-nitro– [1,2,3] triazole-2-ylmethyl) -Isoxazol-3-yl] -ethanone (122 mg, 0.51 mmol) in ethylene glycol (0.57 ml) was treated with trimethyl orthoformate (0.11 ml, 1.3 mmol) followed by LiBF4 (10 mg , 0.10 mmol). The reaction mixture was heated at 95 ° C overnight. Saturated aqueous NaHCO3 (10 ml) was added and the mixture was extracted with EA (2 × 10 ml). The combined extracts were washed with brine (2 × 10 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (40:60 EA-Hept) provided the title compound as a yellow oil. TLC: rf (40:60 EA – Hept) = 0.26. Conditions LC – MS 02: tR = 0.89 min.

2– [3– (2-methyl– [1,3] ddioxolan – 2-yl) –isoxazol-5-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [3– (2-methyl– [1,3] ddioxolan – 2-yl) –isoxazole –5 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (95 mg, 0.34 mmol), iron powder (57 mg, 1.01 mmol) and NH4Cl (91 mg, 1, 69 mmol) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 85 ° C for 15 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by 1N NaOH (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a light yellow oil. LC-MS conditions 02: t R = 0.66 min; [M + H] + = 252.34.

5– (3-Isopropoxymethyl-phenyl) -oxazol-4-carboxylic acid isopropyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (3-hydroxymethyl-phenyl) -oxazole-4-carboxylic acid (200 mg, 0.912 mmol) at 0 ° C in DMF (2.5 ml) it was treated with NaH (239 mg, 5.48 mmol) and the resulting mixture was stirred at 0 ° C for 45 ml. 2-Iodopropane (0.93 ml, 9.12 mmol) was added and the reaction mixture was stirred at room temperature until termination. Saturated aqueous NH4Cl (20 ml) was added and the aqueous layer was extracted twice with EA (2 x 20 ml). The combined organic layers were washed with water (2 x 10 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (1: 1 Hept-EA) provided the title compound as a yellow oil. TLC: rf (1: 1 Hept – EA) = 0.45. LC – MS 02 conditions: t R = 1.05 min, [M + H] + = 304.28.

5– (3-Isopropoxymethyl-phenyl) -oxazol-4-carboxylic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), an isopropyl ester solution of 5– (3-isopropoxymethyl-phenyl) -oxazole-4-carboxylic acid (78 mg, 0.26 mmol) in THF (2.5 ml) was treated with 1N NaOH (1.3 ml). The resulting mixture was stirred for 1.5 h and then acidified with 1N HCl, extracted twice with EA (2 x 20 ml) and the combined organic phases washed with brine (20 ml). The organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a yellow oil. Conditions LC – MS 02: tR = 0.87 min, [M + AcCN + H] + = 303.18.

5– [3– (2-Isopropoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid isopropyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– [3– (2-hydroxy-ethyl) –phenyl] –oxazole-4-carboxylic acid ( 200 mg, 0.86 mmol) in DMF (2.0 ml) was treated at 0 ° C with NaH (112 mg, 2.57 mmol is) and the resulting mixture was stirred for 45 min at 0 ° C. Then 2-iodopropane (0.44 ml, 4.28 mmol) was added and the reaction mixture was stirred at room temperature until completion. The reaction mixture was quenched with saturated aqueous NH4Cl (20 ml), extracted with EA (2 × 20 ml) and the combined organic extracts washed with water (2 × 20 ml) dried over MgSO4, filtered, and the Solvents were removed under reduced pressure. Purification of the residue with FC (1: 1 hept-EA) provided the title compound as a white solid. TLC: rf (1: 1 hept – EA) = 0.49. LC-MS conditions 02: t R = 1.06 min; [M + H] + = 318.36.

(2 – Bromo – thiazol – 5 – yl) –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), commercially obtainable 2-bromo-thiazol-5-carbaldehyde (2,100 g, 10.94 mmol) was dissolved in MeOH (50 ml) NaBH4 (535 mg, 13.58 mmol) was added portionwise at 0 ° C and the reaction mixture was stirred at room temperature for 1 h. Water (50 ml) was added and the mixture was extracted with EA (3 x 50 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow solid. TLC: rf (1: 1 hept – EA) = 0.31. LC-MS conditions 01: t R = 0.56 min; [M + AcCN + H] + = 234.84.

2-Bromo-5– (tert-butyl-dimethyl-silanyloxymethyl) -thiazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), it was dissolved (2-bromo-thiazol-5-yl) -methanol (2.17 g, 11.18 mmol) in CH2Cl2 (30 ml). Tert-butyl dimethylsilyl chloride (1.85 g, 12.30 mmol) was added at 0 ° C, followed by imidazole (1.56 g, 22.92 mmol). The reaction mixture was stirred at room temperature for 16 h. 10% aqueous K2CO3 (10 ml) was added, the layers were separated and the aqueous layer was extracted with CH2Cl2 (2 x 20 ml). The combined extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (hept at 10: 1 hept-EA) provided the title compound as a yellow oil. TLC: rf (2: 1 hept-EA) = 0.80, LC-MS Conditions 02: tR = 1.13 min; [M + H] + = 307.90,

1– [5– (tert-butyl-dimethyl-silanyloxymethyl) -thiazol-2-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-bromine-5- (tert-butyl-dimethyl-silanyloxymethyl) -thiazole (3.00 g, 9.73 mmol) in dry Et2O (20 ml) was added to a solution of n-BuLi (4.30 ml of a 2.5M solution in hexanes, 10.70 mmol) in Et2O (50 ml) at - 78 ° C. The reaction mixture was then stirred for 40 min at -78 ° C before adding N, N-dimethylacetamide (1.81 ml, 19.46 mmol) dropwise. The reaction mixture was allowed to warm to -50 ° C and stirred at this temperature for 20 min. Saturated aqueous NH4Cl (20 ml) was added, the layers were separated and the aqueous layer was extracted with Et2O (3 × 20 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a yellow oil. TLC: rf (1: 2 hept – EA) = 0.80, LC-MS Conditions 01: tR = 1.09 min, [M + H] + = 271.98.

[2– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 5 – yl] –methanol:

In a flame-dried round bottom flask equipped with a magnetic stir bar and a condenser, under an inert atmosphere (N2), a solution of 1– [5– (tert-butyl-dimethyl-silanyloxymethyl) –thiazole – 2-yl] - Ethanone (2.70 g, 9.95 mmol) in ethylene glycol (10.68 ml, 191.48 mmol) was treated with trimethyl orthoformate (2.22 ml, 20.27 mmol) followed by LiBF4 (190 mg, 1.99 mmol). The reaction mixture was heated at 95 ° C for 4 days. Saturated aqueous Na 2CO3 (50 ml) was added and the mixture was extracted with Et2O (2 × 50 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide 3.50 g of an oil of brown in the form of a mixture of 5– (tert-butyl-dimethyl-silanyloxymethyl) –2– (2-methyl– [1,3] dioxolan – 2-yl) –thiazole (TLC: rf (1: 1 hept– EA) = 0.41, Conditions LC – MS 02: tR = 1.11 min, [M + H] + = 316.38) together with [2– (2 – methyl– [1,3] ddioxolan – 2– il) –thiazol – 5 – il] –methanol (TLC: rf

(1: 1 hept – EA) = 0.13, Conditions LC – MS 02: tR = 0.61 min, [M + H] + = 202.47). A solution of this mixture in dry THF (15 ml) was treated at 0 ° C with TBAF (3.0 ml of a 1M solution in THF, 3.00 mmol). The reaction mixture was stirred at 0 ° C for 5 min. and at room temperature for 3 h. The mixture was diluted with EA (10 ml), washed with brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (5: 1 -> 1: 3 hept-EA) provided the title compound as a yellow oil. TLC: rf (1: 2 hept-EA) = 0.20, LC-MS Conditions 01: tR = 0.56 min; [M + H] + = 201.92.

5 – chloromethyl – 2– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [2– (2-methyl– [1,3] ddioxolan – 2 – il) –thiazole – 5 –Il] –methanol (560 mg, 2.78 mmol) in dry CH2Cl2 (5.0 ml) was treated at 0 ° C with 3N Et (0.50 ml, 3.60 mmol) followed by DMAP (34 mg, 0.28 mmol) and Ms-Cl (0.28 ml, 3.51 mmol). After stirring at 0 ° C for 1 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered, and the solvents removed. under reduced pressure. Purification of the residue with FC (5: 1 to 2: 1 hept-EA) provided the title compound as a yellow oil. TLC: rf (1: 2 hept-EA) = 0.50, Conditions LC-MS 01: tR = 0.81 min; [M + H] + = 219.89.

2– [2– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 5-ylmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5-chloromethyl – 2– (2-methyl– [1,3] ddioxolan – 2 – il) - thiazole (339 mg, 1.54 mmol) in DMF (2.0 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (160 mg, 1.40 mmol) in DMF ( 2.0 ml) pre-treated for 30 min with DIPEA (0.48 ml, 2.81 mmol) and the reaction mixture was stirred for 72 h at 50 ° C. It was added to gua (10 ml), followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (5: 1 to 2: 1 hept-EA) provided the title compound as a pale yellow oil: TLC: rf (1: 2 hept-EA) = 0.39. LC-MS conditions 02: t R = 0.89 min; [M + H] + = 298.13.

2– [2– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 5-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole –5 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (201 mg, 0.68 mmol), iron powder (114 mg, 2.03 mmol) and NH4Cl (183 mg, 3, 38 mmol) in a mixture of EtOH (3.0 ml) and water (1.5 ml) was stirred at 75 ° C for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added, followed by 1N NaOH (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil: TLC: rf (19: 1 CH2Cl2 – MeOH) = 0.2. LC-MS conditions 02: t R = 0.68 min; [M + H] + = 268.25.

1 – oxazol – 2 – il – ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a commercially obtainable oxazole solution (3.25 ml, 48.49 mmol) in dry THF (34 ml) at - 15 ° C was treated over a period of 30 min with isopropyl magnesium chloride (24.2 ml of a 2.0M solution in THF, 48.49 mmol) while maintaining the temperature below –10 ° C. The reaction mixture was then stirred for 40 min at -15 ° C before dropping N-methoxy-N-methylacetamide (4.12 ml, 38.79 mmol) in THF (10 ml). The reaction mixture was allowed to warm to room temperature overnight. 20% NH4Cl (150 ml) was added, the layers were separated and the aqueous layer was extracted with Et2O (3 × 100 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC (4: 6 Et2O-hexane) provided the title compound as an orange oil. TLC: rf (4: 6 Et2O-hexane) = 0.27. Conditions LC – MS 02: tR = 0.47 min.

1-oxazol-2-yl-ethanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 1-oxazol-2-yl-ethanone (446 mg, 4.01 mmol) was dissolved in MeOH (8.0 ml) NaBH4 (206 mg,

5.22 mmol) in portions at 0 ° C and the reaction mixture was stirred at room temperature for 30 min. Water (16 ml) was added and the mixture was extracted with EA (3 x 20 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a colorless oil. LC – MS 02 conditions: t R = 0.33 min.

2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 1-oxazol-2-yl-ethanol (348 mg, 3.08 mmol) was dissolved in dry THF (15 ml ). Tert-butyldimethylsilyl chloride (580 mg, 3.85 mmol) was dissolved at room temperature, followed by imidazole (262 mg, 3.85 mmol). The reaction mixture was stirred at room temperature for 16 h. Saturated aqueous NH4Cl (20 ml) was added, the layers were separated and the aqueous layer was extracted with EA (2 x 20 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue by FC

(1: 4 Et2O-hexane) provided the title compound as a colorless oil. TLC: rf (1: 4 Et2O-hexane) = 0.39. LC – MS 02 conditions: tR = 1.08 min, [M + H] + = 228.48

2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole (733 mg, 3.22 mmol) in dry THF (16 ml) at –78 ° C was treated with t-butyllithium (2.62 ml of a 1.6M solution in pentane, 4.19 mmol) while maintaining the temperature below –70 ° C The reaction mixture was then stirred for 1 h at –40 ° C. DMF (0.50 ml, 6.45 mmol) was added dropwise at -78 ° C. The reaction mixture was allowed to warm to room temperature and stirred for 2 h at room temperature. Water (30 ml) was added followed by saturated aqueous NH4Cl (20 ml) and EA (20 ml), the layers were separated and the aqueous layer was extracted with EA (2 × 30 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC

(1: 4 EA – Hept) provided the title compound as a colorless oil. TLC: rf (1: 4 EA – Hept) = 0.33. LC – MS 02 conditions: t R = 1.08 min, [M + H] + = 256.38.

{2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-yl} -methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole – 5 – carbaldehyde ( 457 mg, 1.79 mmol) in MeOH (8.0 ml). NaBH4 (92 mg, 2.33 mmol) was added dropwise at 0 ° C and the reaction mixture was stirred at room temperature for 20 min. Water (16 ml) was added and the mixture was extracted with EA (3 x 20 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a colorless oil. LC-MS 02 conditions: t R = 0.97 min, [M + H] + = 258.32.

2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -5-chloromethyl-oxazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole – 5– il} -methanol (455 mg, 1.77 mmol) in dry CH2Cl2 (4.5 ml) was treated at 0 ° C with Et 3N (0.32 ml, 2.30 mmol) followed by DMAP (22 mg, 0 , 18 mmol) and Ms-Cl (0.17 ml, 2.12 mmol). After stirring at room temperature for 2 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered, and the solvents removed under reduced pressure to provide the title compound in a 2: 1 ratio. (Conditions LC – MS 02: tR = 1.13 min, [M + H] + = 276.06) together with ester 2– [1– (tert-butyl-dimethyl-silanyloxy) - ethyl] –oxazol – 5-ylmethyl methanesulfonic acid (Conditions LC – MS 02: tR = 1.07 min, [M + H] + = 336.45) in the form of a pale yellow oil.

2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -4-nitro-2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –5 – chloromethyl-oxazole (247 mg, 0.89 mmol) in DMF (1.0 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (850 mg of a 10% solution in acetone, 0 , 75 mmol) in DMF (1.0 ml) pre-treated for 30 min with DIPEA (0.26 ml, 1.49 mmol) and the reaction mixture was stirred for 48 h at 50 ° C. Water (10 ml) was added, followed by EA (20 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (2: 1 hept-EA) provided the title compound as a yellow oil. TLC: rf (2: 1 hept – EA) = 0.36. LC-MS conditions 02: t R = 1.11 min; [M + H] + = 354.34.

2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole– 5-ylmethyl} -4-nitro-2H- [1,2,3] triazole (100 mg, 0.28 mmol), iron powder (48 mg, 0.85 mmol) and NH4Cl (76 mg, 1.42 mmol) in a mixture of EtOH (2.0 ml) and water (1.0 ml) was stirred at 85 ° C for 20 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added, followed by water (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a yellow oil. LC-MS conditions 02: t R = 0.98 min; [M + H] + = 324.42.

(2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazol-4-yl) -amide of acid 5– phenyl-oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5-phenyl-oxazol-4-carboxylic acid (47 mg, 0.25 mmol) in CH2Cl2 (1 , 5 ml) was treated at room temperature with HOBt (40 mg, 0.30 mmol), EDC (119 mg, 0.62 mmol), DMAP (8 mg, 0.06 mmol) and the resulting mixture was stirred at temperature ambient for 30 min. Then 2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazole-4-ylamine (80 mg, 0 , 25 mmol) in CH2Cl2 (1.0 ml) and the resulting mixture was stirred at room temperature for 72 h. CH2Cl2 (20 ml) was added followed by water (15 ml) and the aqueous phase was extracted with CH2Cl2. The combined organic phases were washed with water, brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a yellow oil. Conditions LC-MS 02: t R = 1.17 min, [M + H] + = 495.54.

{2– [2– (1-hydroxy-ethyl) –oxazol-5-ylmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 5-phenyl-oxazol-4-carboxylic acid

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (2– {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole –5 – ylmethyl} –2H– [1,2,3] triazol-4-yl) -5-phenyl-oxazol-4-carboxylic acid amide (120 mg, 0.24 mmol) in dry THF (2.1 ml) was treated at 0 ° C with TBAF (0.48 ml of a 1M solution in THF, 0.48 mmol). The reaction mixture was stirred at 0 ° C for 45 min. The mixture was then diluted with EA (10 ml), washed with NaHCO3 (10 ml) followed by brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (19: 1 CH2Cl2-MeOH) provided the title compound as a white foam. TLC: rf (19: 1 CH2Cl2-MeOH) = 0.19. LC-MS conditions 02: t R = 0.88 min; [M + H] + = 381.23.

1– (2 – Bromo – thiazol – 5 – yl) –ethanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a commercially obtainable solution of 2-bromo-thiazol-5-carbaldehyde (1.80 g, 9.37 mmol) in CH2Cl2 (70.0 ml) was treated at 0 ° C with trimethyl aluminum (4 6.0 ml of a 1M solution in heptane, 46 mmol). The reaction mixture was then stirred at 0 ° C for 45 min. Then CH2Cl2 (100.0 ml) was added followed by saturated aqueous NH4Cl (100 ml). The mixture was treated with 1N HCl (50 ml) and the aqueous layer was extracted with CH2Cl2 (150 ml). The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil. TLC: rf (1: 2 hept-EA) = 0.40, LC-MS Conditions 02: tR = 0.70 min; [M + AcCN + H] + = 249.17.

1– (2 – bromo – thiazol – 5 – il) –ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– (2 – bromo – thiazol – 5 – yl) –ethanol (1.95 g, 9, 37 mmol) in AcCN (90.0 ml) was treated at room temperature with MnO2 (4.53 g, 46.86 mmol) and the reaction mixture was stirred for 16 h at room temperature before filtering through Celite. The solvent was removed under reduced pressure to provide the title compound as a yellow solid. Conditions LC – MS 02: tR = 0.80 min.

2 – Bromo – 5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazole:

In a flame-dried round bottom flask equipped with a magnetic stir bar and a condenser under an inert atmosphere (N2), a solution of 1– (2 – bromo – thiazol – 5 – yl) –ethanone (2.20 g, 10 , 68 mmol) in ethylene glycol (11.46 ml, 205.53 mmol) was treated with trimethyl orthoformate (2.39 ml, 21.76 mmol) followed by LiBF4 (204 mg, 2.14 mmol). The reaction mixture was heated at 95 ° C for 2 days. Saturated aqueous NaHCO 3 (50 ml) was added and the mixture was extracted with EA (50 ml). The organic extracts were washed with brine (2 × 50 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (20: 1 a

3: 1 hept-EA) provided the title compound as a yellow solid. TLC: rf (1: 1 hept-EA) = 0.80, LC-MS Conditions 01: tR = 0.84 min; [M + H] + = 251.85.

5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazole – 2 – carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-bromine-5- (2-methyl- [1,3] d dioxolan-2-il) -Thiazole (780 mg, 3.12 mmol) in dry Et2O (10 ml) was added to a solution of n-BuLi (1.25 ml of a 2.5 M solution in hexanes, 3.13 mmol) in Et2O ( 10 ml) at –78 ° C. The reaction mixture was then stirred for 30 min at -78 ° C before adding DMF drip (0.29 ml, 3.78 mmol). The reaction mixture was allowed to warm to -20 ° C and stirred at this temperature for 20 min. Saturated aqueous NH4Cl (10 ml) was added, the layers were separated and the aqueous layer was extracted with Et2O (3 × 10 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (10: 1 to 3: 1 hept-EA) provided the title compound as a yellow solid. TLC: rf (1: 1 hept-EA) = 0.50, LC-MS Conditions 01: tR = 0.78 min; [M + H] + = 199.93.

[5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 5– (2-methyl– [1,3] dioxolan-2-yl) -thiazole-2-carbaldehyde (555 mg, 2.79 mmol) was dissolved in MeOH (5 ml). NaBH4 (136 mg, 3.46 mmol) was added portionwise at 0 ° C and the reaction mixture was stirred at room temperature for 1 h. Water (10 ml) was added and the mixture was extracted with EA (3 x 20 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil. TLC: rf (1: 1 hept – EA) = 0.25. LC-MS conditions 02: t R = 0.64 min; [M + H] + = 202.48.

5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole-2-yl methyl ester of methanesulfonic acid

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [5– (2-methyl– [1,3] ddioxolan – 2 – il) –thiazole – 2 –Il] –methanol (560 mg, 2.78 mmol) in dry CH2Cl2 (5.0 ml) was treated at 0 ° C with 3N Et (0.50 ml, 3.60 mmol) followed by DMAP (34 mg, 0.28 mmol) and Ms-Cl (0.28 ml, 3.51 mmol). After stirring at 0 ° C for 1 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (5: 1 to 2: 1 hept-EA) provided the title compound as a brown solid. LC-MS conditions 01: t R = 0.77 min; [M + H] + = 279.88.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] –4-nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), an ester solution 5– (2-methyl– [1,3] ddioxolan – 2 – il) –thiazole – 2– Methanesulfonic acid ilmethyl (445 mg, 1.59 mmol) in DMF (3.0 mL) was added a solution of 4-nitro-2H– [1,2,3] triazole (180 mg, 1.58 mmol) in DMF (3.0 ml) pre-treated for 30 min with DIPEA (0.54 ml, 3.16 mmol) and the reaction mixture was stirred for 72 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (5: 1 to 2: 1 hept-EA) provided the title compound as a pale yellow oil: TLC: rf (1: 2 hept-EA) = 0.39. LC-MS conditions 01: t R = 0.85 min; [M + H] + = 297.91.

2– [5– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole –2 – ilmethyl] –4 – nitro – 2H– [1,2,3] triazole (220 mg, 0.74 mmol), iron powder (125 mg, 2.22 mmol) and NH4Cl (200 mg, 3.70 mmol) in a mixture of EtOH (3.0 ml) and water (1.5 ml) was stirred at 75 ° C for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. CH2Cl2 (10 ml) was added followed by 1N NaOH (10 ml). The aqueous layer was extracted with CH2Cl2 (2 × 10 ml) and the combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil: TLC: rf (19: 1 CH2Cl2 – MeOH) = 0.2. Conditions LC – MS 02: tR = 0.66 min.

(4 – bromo – thiophene – 2 – il) –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 4-bromo-thiophene-2-carbaldehyde (3.93 g, 20.57 mmol) commercially obtainable, it was dissolved in THF (60.0 ml). NaBH4 (892 mg, 22.63 mmol) was added portionwise at 0 ° C and the reaction mixture was stirred at room temperature for 30 min. Saturated aqueous NaHCO3 was added and the mixture was extracted with Et2O. The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a colorless oil. TLC: rf (2: 1 hept – EA) = 0.38.

(4-Bromo-thiophene-2-ylmethoxy) -ter-butyl-dimethyl-silane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), (4-bromo-thiophene-2-yl) -methanol (3.97 g, 20.57 mmol) dissolved in dry CH2Cl2 (50 ml). Ter-Butyldimethylsilyl chloride (3.59 g, 22.63 mmol) was added at room temperature, followed by imidazole (1.56 g, 22.63 mmol). The reaction mixture was stirred at room temperature for 1 h. Water was added, the layers were separated and the organic layer was dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (hept) provided the title compound as a colorless oil. TLC: rf (100: 1 hept – EA) = 0.44. Conditions LC – MS 02: tR = 1.21 min.

1– [5– (tert-butyl-dimethyl-silanyloxymethyl) -thiophene-3-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (4-bromo-thiophene-2-ylmethoxy) -ter-butyl-dimethyl-silane (3) was added , 07 g, 10.00 mmol) in dry Et2O (10 ml) to a solution of n-butyllithium (4.10 ml of a 2.5 M solution in hexane, 10.25 mmol) in Et2O (40 ml) at –78 ° C while maintaining the temperature po r below –70 ° C. The reaction mixture was then stirred for 30 min at –78 ° C. N, N-dimethyl-acetamide (1.20 ml, 12.91 mmol) was added dropwise at -78 ° C. The reaction mixture was then stirred for 1 h at –78 ° C, followed by 1 h at room temperature. Saturated, aqueous NH4Cl was added, the layers were separated and the aqueous layer was extracted with Et2O (3 × 50 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (0: 100 to 10:90 EA-Hept) provided the title compound as a yellow solid. TLC: rf (1: 9 EA –Hept) = 0.30, Conditions LC – MS 02: tR = 1.15 min.

tert-butyl-dimethyl– [4– (2-methyl– [1,3] ddioxolan-2-yl) -thiophene-2-ylmethoxy] -silane:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and a condenser under an inert atmosphere (N2), a solution of 1– [5– (tert-butyl-dimethyl-silanyloxymethyl) –thiophe-3-yl] -Ethanone (811 mg, 3.00 mmol) in ethylene glycol (3.5 ml, 62.76 mmol) was treated with trimethyl orthoformate (0.66 ml, 6.02 mmol) followed by LiBF4 (57 mg, 0 , 60 mmol). The reaction mixture was heated at 95 ° C for 2 h. Saturated aqueous Na 2CO3 (50 ml) was added and the mixture was extracted with Et2O (2 × 50 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (1:20 EA-Hept) provided the title compound as a yellow oil. TLC: rf (1:10 EA – Hept) = 0.34. LC-MS conditions 02: t R = 1.17 min; [M + H] + = 315.22.

[4– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiophene – 2 – yl] –methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of tert-butyl-dimethyl– [4– (2-methyl– [1,3] ddioxolan – 2– il) -thiophene-2-ylmethoxy] -silane (545 mg, 1.73 mmol) in dry THF (5.0 ml) was treated at 0 ° C with TBAF (2.6 ml of a 1M solution in THF, 2.60 mmol). The reaction mixture was stirred at 0 ° C for 2 h. The mixture was then diluted with EA (10 ml), washed with brine (3 x 20 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (1: 5 EA-Hept) provided the title compound as a colorless oil. TLC: rf (1: 1 EA – Hept) = 0.36. Conditions LC – MS 02: tR = 0.70 min.

2– [4– (2 – methyl– [1,3] ddioxolan – 2-yl) –thiophene – 2-ylmethyl] –4 – nitro – 2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [4– (2-methyl– [1,3] d dioxolan – 2 – il) –tiofen– 2-yl] -methanol (256 mg, 1.28 mmol) in dry CH2Cl2 (5.0 ml) was treated at 0 ° C with 3N Et (0.23 ml, 1.64 mmol) followed by DMAP (16 mg , 0.13 mmol) and Ms-Cl (0.12 ml, 1.55 mmol). After stirring at 0 ° C for 30 min and at room temperature for 1 h, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered , and the solvents were removed under reduced pressure to provide 2– (5-chloromethyl- thiophene-3-yl) –2-methyl– [1,3] crude dioxolane (TLC: rf (1: 1 EA – Hept) = 0 , 61). A solution of the crude technician in DMF (3 ml) was treated at room temperature with a solution of (4-nitro-2H– [1,2,3] triazole (124 mg, 1.07 mmol) in DMF (2.0 ml) pre-treated for 30 min with DIPEA (0.40 ml, 2.34 mmol) The resulting reaction mixture was stirred for two weeks at room temperature Water (10 ml) was added, followed by EA (10 ml The organic extract was washed with water (10 ml), dried over Na2SO4, filtered and the solvents removed under reduced pressure Purification of the residue with FC (hept at 1: 1 hept-EA) provided the compound of title in the form of a yellow oil: TLC: rf (1: 1 hept – EA) = 0.48.

2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene – 2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 1– [4– (2-methyl– [1,3] ddioxolan – 2 – il) –tiofen –2 – ilmethyl] –4 – nitro – 1H – pyrazole (115 mg, 0.39 mmol), iron powder (65 mg, 1.16 mmol) and NH4Cl (106 mg, 1.97 mmol) in a mixture of EtOH (3.0 ml) and water (1.5 ml) was stirred at 75 ° C for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. The filtrate was dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to give the title compound as a yellow oil: TLC: rf (EA) = 0.63. LC-MS conditions 02: t R = 0.76 min; [M + H] + = 267.09.

Ethyl ester of (E) -2-styryl-oxazol-4-carboxylic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a suspension of 3-phenyl-acrylamide (10.31 g, 67.95 mmol) and NaHCO3 (28.47 g , 339.73 mmol) in THF (260 ml) was treated with 3-bromo-2-oxo-propionic acid ethyl ester (13.04 ml, 88.33 mmol) and the reaction mixture was heated at reflux for 15 h. 3-Bromo-2-oxo-propionic acid ethyl ester (13.04 ml, 88.33 mmol) was added again and the reaction mixture was stirred at reflux for 15 h. The reaction mixture was then filtered over celite and the solvents evaporated under reduced pressure. The residue was dissolved in THF (30 ml) and treated at 0 ° C, dropwise, with trifluoroacetic anhydride (30.0 ml, 215.83 mmol). The reaction mixture was then stirred at room temperature overnight. Aqueous saturated Na2CO3 was added, and the mixture was extracted with EA (3 × 150 ml), dried over MgSO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (1: 9 EA-Hept) provided the title compound as a yellow solid. TLC: rf (1: 9 EA – Hept) = 0.1. LC-MS conditions 02: t R = 1.01 min; [M + H] + = 244.48.

2-Formyl-oxazol-4-carboxylic acid ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of NaIO4 (3.21 g, 15.00 mmol) in water (26.0) ml was added slowly to a vigorously stirred suspension of silica gel (15.0 g) in acetone (60.0 ml). The mixture was then concentrated under reduced pressure and the lumpy solid was suspended in CH2Cl2 and the solvent was evaporated under reduced pressure. CH2Cl2 (40.0 ml) was added and the reaction mixture was treated at room temperature with ethyl ester of (E) -2-styryl-oxazol-4-carboxylic acid (1.22 g, 5.00 mmol) and hydrate of RuCl3 (82 mg, 0.15 mmol). The reaction mixture was stirred at room temperature in the dark for 30 min, filtered and concentrated under reduced pressure. Purification of the residue with FC (1: 9 to 1: 2 EA-Hept) provided the title compound as a yellow solid. TLC: rf (3: 2 EA – Hept) = 0.21. LC-MS conditions 02: t R = 0.51 min; [M + H2O + H] + = 188.50,

2-Hydroxymethyl-oxazol-4– ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 2-formyl-oxazol-4-carboxylic acid ethyl ester (272 mg, 1.61 mmol) was dissolved in EtOH (5.0 ml). NaBH4 (112 mg, 2.84 mmol) was added portionwise at 0 ° C and the reaction mixture was stirred at 0 ° C for 1 h. Aqueous saturated NH4Cl was added, and the mixture was extracted with EA (5 × 10 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil. TLC: rf (EA) = 0.50, Conditions LC-MS 02: tR = 0.58 min; [M + H] + = 172.03.

2– (tert-Butyl-dimethyl-silanyloxymethyl) -oxazol-4-carboxylic acid ethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), 2-hydroxymethyl-oxazol-4-carboxylic acid ethyl ester (275 mg, 1.61 mmol) was dissolved in CH2Cl2 dry (5.0 ml). Tert-butyl dimethylsilyl chloride (510 mg, 3.22 mmol) was added at room temperature, followed by imidazole (221 mg, 3.22 mmol). The reaction mixture was stirred at room temperature for 30 min. Water was added, the layers were separated and the organic layer was dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (1:20 to 1: 9 EA-Hept) provided the title compound as a colorless oil. TLC: rf (9: 1 hept – EA) = 0.15. LC-MS conditions 02: t R = 1.10 min; [M + H] + = 286.38.

2– (tert-butyl-dimethyl-silanyloxymethyl) -oxazol-4-carbaldehyde:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– (tert-butyl-dimethyl-silanyloxymethyl) -oxazole-4-carboxylic acid ethyl ester (283 mg, 0.99 mmol) in CH2Cl2 (5.0 ml) was treated at -78 ° C with DiBAL (1.85 ml of a 1M solution in toluene, 1.85 mmol) and the reaction mixture was stirred for 1 ha –78 ° C. MeOH (70 µL) and H2O (100 µL) were added, the reaction mixture was allowed to warm to room temperature. The reaction mixture was filtered, and the solvent was removed under reduced pressure, to provide the title compound as a colorless oil. TLC: rf (1: 1 hept – EA) = 0.61. LC-MS conditions 02: t R = 1.03 min; [M + H2O + H] + = 260.50,

1– [2– (tert-butyl-dimethyl-silanyloxymethyl) -oxazol-4-yl] -ethanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol – 4 – carbaldehyde (223 mg, 0, 92 mmol) in CH2Cl2 (8.0 ml) was treated at 0 ° C with trimethyl aluminum (2.50 ml of a 2M solution in toluene, 5.00 mmol). The reaction mixture was then stirred at 0 ° C for 45 min. Aqueous saturated NH4Cl was then added and the aqueous layer was extracted twice with CH2Cl2 and twice with EA. The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a colorless oil. TLC: rf (1: 1 hept – EA) = 0.32. LC – MS 02 conditions: tR = 0.97 min, [M + H] + = 258.30,

1– [2– (tert-butyl-dimethyl-silanyloxymethyl) -oxazol-4-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– [2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol – 4-yl] –ethanol (193 mg, 0.75 mmol) in AcCN (5.0 ml) was treated at room temperature with MnO2 (362 mg, 3.75 mmol). The reaction mixture was stirred for 16 h at room temperature before filtering through Celite. The solvent was removed under reduced pressure to provide the title compound as a white solid. TLC: rf (1: 1 hept – EA) = 0.69. LC – MS conditions

02: tR = 1.04 min, [M + H] + = 255.84.

1– (2-hydroxymethyl-oxazol-4-yl) -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– [2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol – 4-yl] –ethanone (192 mg, 0.75 mmol) in dry THF (5.0 ml) was treated at room temperature with TBAF (1.1 ml of a 1M solution in dry THF, 1.10 mmol). The reaction mixture was stirred at room temperature for 1.5 h. The mixture was then diluted with EA (10 ml), washed with brine (3 x 10 ml), dried over Na2SO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (1: 1 to 2: 1 EA-Hept) provided the title compound as a pale yellow solid. TLC: rf (EA) = 0.37. LC-MS 02 conditions: t R = 0.34 min, [M + H] + = 142.46.

Methanesulfonic acid 4-acetyl-oxazol-2-ylmethyl ester:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 1– (2-hydroxymethyl-oxazol-4-yl) –ethanone (75 mg, 0.53 mmol ) in dry CH2Cl2 (5.0 ml) was treated at 0 ° C with Et 3N (0.10 ml, 0.71 mmol) followed by DMAP (6 mg, 0.05 mmol) and Ms-Cl (0.05 ml, 0.66 mmol). After stirring at 0 ° C for 30 min, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered, and the solvents were removed. under reduced pressure to provide the title compound as a yellow oil. TLC: rf (EA) = 0.63. LC-MS conditions 02: t R = 0.64 min; [M + H] + = 220.22.

1– [2– (4 – nitro– [1,2,3] triazol-2-ylmethyl) –oxazol – 4-yl] –ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 4-acetyl-oxazol-2-yl methyl ester of methanesulfonic acid (116 mg, 0.53 mmol) in DMF (3.0 ml) was added to a solution of 4-nitro-2H- [1,2,3] triazole (62 mg, 0.53 mmol) in DMF (2.0 ml) pretreated for 30 min with DIPEA (0.20 ml, 1.17 mmol) and the reaction mixture was stirred for 20 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (3: 1 to 1: 1 hept-EA) provided the title compound as a yellow solid. TLC: rf (1: 2 hept – EA) = 0.49. Conditions LC – MS 01: tR = 0.76 min.

1– [2– (4-amino– [1,2,3] triazol-2-ylmethyl) -oxazol-4-yl] -ethanone:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a mixture of 1– [2– (4-nitro– [1,2,3] triazole-2-ylmethyl) -Oxazol-4-yl] -ethanone (48 mg, 0.20 mmol), iron powder (34 mg, 0.61 mmol) and NH4Cl (54 mg, 1.01 mmol) in a mixture of EtOH (2, 0 ml) and water (1.0 ml) was stirred at 75 ° C for 60 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. The filtrate was dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a brown oil. TLC: rf (EA) = 0.40, LC-MS Conditions 02: tR = 0.54 min; [M + H] + = 208.44.

(2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazol-4-yl) -amide of acid 5– (3– fluorophenyl) -2-methyl-oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (3-fluorophenyl) -2-methyl-oxazole-4-carboxylic acid (34 mg , 0.16 mmol) in CH2Cl2 (1.0 mL) was treated at room temperature with HOBt (25 mg, 0.19 mmol), EDC (74 mg, 0.38 mmol), DMAP (5 mg, 0.04 mmol) and the resulting mixture was stirred at room temperature for 30 min. Then 2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazole-4-ylamine (50 mg, 0 , 16 mmol) in CH2Cl2 (0.6 ml) and the resulting mixture was stirred at room temperature for 16 h. CH2Cl2 (20 ml) was added followed by water (15 ml) and the aqueous phase was extracted with CH2Cl2. The organic phases were washed with water, brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to give the title compound as a brown oil. LC-MS 02 conditions: t R = 1.22 min, [M + H] + = 527.5.

{2– [2– (1-hydroxy-ethyl) –oxazol-5-ylmethyl] –2H– [1,2,3] triazol-4-yl} -amide of acid 5– (3-fluor-phenyl) - 2-methyl-oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (2– {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole –5 – ilmethyl} –2H– [1,2,3] triazol-4-yl) - 5– (3-fluorophenyl) -2-methyl-oxazol-4-carboxylic acid amide (110 mg, 0, 21 mmol) in dry THF (2.1 ml) was treated at 0 ° C with TBAF (0.42 ml of a 1M solution in THF, 0.4 2 mmol). The reaction mixture was stirred at 0 ° C for 45 min. The mixture was then diluted with EA (10 ml), washed with NaHCO3 (10 ml) followed by brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (19: 1 CH2Cl2-MeOH) provided the title compound as an orange oil. TLC: rf (19: 1 CH2Cl2-MeOH) = 0.21. LC-MS conditions 02: t R = 0.94 min; [M + H] + = 412.86.

(2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H– [1,2,3] triazol-4-yl) -amide of acid 2– methyl– 5 – m – tolyl – oxazol – 4 – carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid (34 mg, 0.16 mmol) in CH2Cl2 (1.0 ml) was treated at room temperature with HOBt (25 mg, 0.19 mmol), EDC (74 mg, 0.38 mmol), DMAP (5 mg, 0.04 mmol) and the The resulting mixture was stirred at room temperature for 30 min. Then 2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazole-4-ylamine (50 mg, 0 , 16 mmol) in CH2Cl2 (0.6 ml) and the resulting mixture was stirred at room temperature for 16 h. CH2Cl2 (20 ml) was added followed by water (15 ml) and the aqueous phase was extracted with CH2Cl2. The combined organic phases were washed with water, brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a brown oil. LC – MS 02 conditions: t R = 1.23 min, [M + H] + = 523.56.

{2– [2– (1-hydroxy-ethyl) –oxazol-5-ylmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 2-methyl-5-m-tolyl acid– oxazol – 4– carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (2– {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole –5 – ylmethyl} –2H– [1,2,3] triazol-4-yl) - 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid amide (109 mg, 0.21 mmol) in Dry THF (2.0 ml) was treated at 0 ° C with TBAF (0.41 ml of a 1M solution in THF, 0.41 mmol). The reaction mixture was stirred at 0 ° C for 4-5 min. The mixture was then diluted with EA (10 ml), washed with NaHCO3 (10 ml) followed by brine (3 x 10 ml), dried over MgSO4, filtered and garlic concentrated under reduced pressure. Purification of the residue with FC (19: 1 CH2Cl2-MeOH) provided the title compound as a yellow oil. TLC: rf (19: 1 CH2Cl2-MeOH) = 0.23. LC-MS conditions 02: t R = 0.95 min; [M + H] + = 409.78.

(2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazol-4-yl) -amide of acid 5– (3– chloro-phenyl) -2-methyl-oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5– (3-chloro-phenyl) -2-methyl-oxazole-4-carboxylic acid (37 mg , 0.16 mmol) in CH2Cl2 (1.0 mL) was treated at room temperature with HOBt (25 mg, 0.19 mmol), EDC (74 mg, 0.38 mmol), DMAP (5 mg, 0.04 mmol) and the resulting mixture was stirred at room temperature for 30 min. Then 2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazole-4-ylamine (50 mg, 0 , 16 mmol) in CH2Cl2 (0.6 ml) and the resulting mixture was stirred at room temperature for 16 h. CH2Cl2 (20 ml) was added followed by water (15 ml) and the aqueous phase was extracted with CH2Cl2. The combined organic phases were washed with water, brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a brown oil. LC-MS 02 conditions: t R = 1.24 min, [M + H] + = 542.92.

{2– / 2– (1-hydroxy-ethyl) –oxazol-5-ylmethyl] –2H– [1,2,3] triazol-4-yl} (3-chloro-phenyl) -2-methyl acid amide - oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (2– {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole –5 – ilmethyl} –2H– [1,2,3] triazol-4-yl) - 5– (3-chloro-phenyl) -2-methyl-oxazol-4-carboxylic acid amide (106 mg, 0, 20 mmol) in dry THF (1.9 ml) was treated at 0 ° C with TBAF (0.39 ml of a 1M solution in THF, 0.3 9 mmol). The reaction mixture was stirred at 0 ° C for 45 min. The mixture was then diluted with EA (10 ml), washed with NaHCO3 (10 ml) followed by brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (19: 1 CH2Cl2-MeOH) provided the title compound as a white solid. TLC: rf (19: 1 CH2Cl2-MeOH) = 0.22. LC-MS conditions 01: t R = 0.93 min; [M + H] + = 428.97.

(2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazol-4-yl) -amide of acid 5– m– tolyl-oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 5-m-tolyl-oxazol-4-carboxylic acid (31 mg, 0.16 mmol) in CH2Cl2 (1.0 ml) was treated at room temperature with HOBt (25 mg, 0.19 mmol), EDC (74 mg, 0.38 mmol), DMAP (5 mg, 0.04 mmol) and the resulting mixture was stirred at room temperature for 30 min. Then 2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazole-4-ylamine (50 mg, 0 , 16 mmol) in CH2Cl2 (0.6 ml) and the resulting mixture was stirred at room temperature for 16 h. CH2Cl2 (20 ml) was added followed by water (15 ml) and the aqueous phase was extracted with CH2Cl2. The combined organic phases were washed with water, brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a brown oil. LC-MS conditions 02: t R = 1.20 min, [M + H] + = 509.55.

{2– [2– (1-hydroxy-ethyl) –oxazol-5-ylmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 5-m-tolyl-oxazole-4– carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (2– {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole –5 – ilmethyl} –2H– [1,2,3] triazol-4-yl) - 5-m-tolyl-oxazol-4-carboxylic acid amide (100 mg, 0.20 mmol) in dry THF (1 , 9 ml) was treated at 0 ° C with TBAF (0.39 ml of a 1M solution in THF, 0.39 mmol). The reaction mixture was stirred at 0 ° C for 45 min. The mixture was then diluted with EA (10 ml), washed with NaHCO3 (10 ml) followed by brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (19: 1 CH2Cl2-MeOH) provided the title compound as a yellow oil. TLC: rf (19: 1 CH2Cl2-MeOH) = 0.21. LC-MS conditions 02: t R = 0.92 min; [M + H] + = 395.35.

(2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H– [1,2,3] triazol-4-yl) -amide of acid 2– methyl– 5– (3-trifluoromethoxy-phenyl) -oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-methyl-5- (3-trifluoromethoxy-phenyl) -oxazole-4-carboxylic acid (44 mg , 0.16 mmol) in CH2Cl2 (1.0 mL) was treated at room temperature with HOBt (25 mg, 0.19 mmol), EDC (74 mg, 0.38 mmol), DMAP (5 mg, 0.04 mmol) and the resulting mixture was stirred at room temperature for 30 min. Then 2– {2– [1– (tert-butyl-dimethyl-silanyloxy) -ethyl] -oxazol-5-ylmethyl} -2H- [1,2,3] triazole-4-ylamine (50 mg, 0 , 16 mmol) in CH2Cl2 (0.6 ml) and the resulting mixture was stirred at room temperature for 16 h. CH2Cl2 (20 ml) was added followed by water (15 ml) and the aqueous phase was extracted with CH2Cl2. The combined organic phases were washed with water, brine, dried over MgSO4, filtered, and the solvent was removed under reduced pressure to provide the title compound as a brown oil. . LC – MS 02 conditions: tR = 1.25 min, [M + H] + = 593.58.

{2– [2– (1-hydroxy-ethyl) –oxazol-5-ylmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 2-methyl-5– (3-trifluoromethoxy acid) - phenyl) -oxazol-4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of (2– {2– [1– (tert-butyl-dimethyl-silanyloxy) –ethyl] –oxazole –5 – ilmethyl} –2H– [1,2,3] triazol-4-yl) - 2-methyl-5– (3-trifluoromethoxy-phenyl) -oxazole-4-carboxylic acid amide (122 mg, 0, 21 mmol) in dry THF (2.0 ml) was treated at 0 ° C with TBAF (0.41 ml of a 1M solution in THF, 0.41 mmol). The reaction mixture was stirred at 0 ° C for 45 min. The mixture was then diluted with EA (10 ml), washed with NaHCO3 (10 ml) followed by brine (3 x 10 ml), dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (19: 1 CH2Cl2-MeOH) provided the title compound as a white solid. TLC: rf (19: 1 CH2Cl2-MeOH) = 0.26. LC-MS conditions 02: t R = 1.01 min; [M + H] + = 479.03.

[2– (tert-Butyl-dimethyl-silanyloxymethyl) -oxazol-4-yl] -methanol:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of ethyl ester of 2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazole-4-carboxylic acid (830 mg, 2.91 mmol) in THF (15.0 ml) was treated at 0 ° C with IDAL (11.6 ml of a 1M solution in toluene, 11.60 mmol) and the reaction mixture was stirred for 45 min at 0 ° C. The reaction mixture was then diluted with EA (5.0 ml), Rochelle salt (20.0 ml) was added and the mixture was stirred at room temperature for 2 h. The layers were separated and the aqueous layer was extracted with EA (3 × 20 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow solid. TLC: rf (EA) = 0.59. LC-MS conditions 02: t R = 0.94 min; [M + H] + = 244.46.

2 - (tert-Butyl-dimethyl-silanyloxymethyl) -oxazol-4-yl-methyl ester of methanesulfonic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of [2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol-4-yl] -methanol (500 mg, 2.05 mmol) in dry CH2Cl2 (10.0 ml) was treated at 0 ° C with Et 3N (0.37 ml, 2.65 mmol) followed by DMAP (25 mg, 0.20 mmol) and Ms - Cl (0.20 ml, 2.54 mmol). After stirring at 0 ° C for 30 min, the reaction mixture was quenched with water (10 ml), extracted with CH2Cl2 (10 ml) and the combined organic extracts dried over Na2SO4, filtered, and the solvents were removed. under reduced pressure to provide the title compound as a yellow oil. TLC: rf (1: 1 hept-EA) = 0.50, LC-MS Conditions 02: tR = 1.05 min; [M + H] + = 322.25.

2– [2– (tert-butyl-dimethyl-silanyloxymethyl) -oxazol-4-ylmethyl] -4-nitro-2H– [1,2,3] triazole:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of ester 2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol-4-ylmethyl methanesulfonic acid (651 mg, 2.02 mmol) in DMF (3.0 ml) was added to a solution of 4-nitro-2H– [1,2,3] triazole (210 mg, 1.84 mmol) in DMF (3.0 ml) pre-treated for 30 min with DIPEA (0.63 ml, 3.68 mmol) and the reaction mixture was stirred for 20 h at 50 ° C. Water (10 ml) was added, followed by EA (10 ml). The aqueous layer was extracted with EA (10 ml) and the combined organic extracts were dried over NaSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue with FC (5: 1 to 2: 1 hept-EA) provided the title compound as a yellow oil: TLC: rf (1: 2 hept-EA) = 0.30, LC Conditions –MS 02: t R = 1.10 min; [M + H] + = 340.47.

2– [2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol-4-ylmethyl] –2H– [1,2,3] triazole-4-ylamine:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– [2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol – 4 – ylmethyl] –4 –Nitro – 2H– [1,2,3] triazole (103 mg, 0.30 mmol), iron powder (51 mg, 0.91 mmol) and NH4Cl (82 mg, 1.52 mmol) in a mixture of EtOH (3.0 ml) and water (1.5 ml) was stirred at 75 ° C for 90 min. The reaction mixture was filtered while hot and concentrated under reduced pressure. The residue was redissolved in CH2Cl2 (20 ml), dried over Na2SO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow oil. TLC: rf (19: 1 CH2Cl2-MeOH) = 0.20, LC-MS Conditions 02: tR = 0.96 min; [M + H] + = 310.46.

{2– [2– (tert-Butyl-dimethyl-silanyloxymethyl) -oxazol-4-ylmethyl] -2H- [1,2,3] triazole-4-yl} -carbamic acid 2-chloro-benzyl ester

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– [2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazol – 4-ylmethyl] –2H - [1,2,3] triazol-4-ylamine (93 mg, 0.30 mmol) in CH2Cl2 (5.0 ml) was treated with DIPEA (0.08 ml, 0.48 mmol) followed by 2-chlorobenzyl chloroformate (0.06 ml, 0.39 mmol) at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 h and added or water (5.0 ml). The layers were separated and the aqueous layer was extracted with CH2Cl2 (2 × 10 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvent was removed under reduced pressure. Purification of the residue with FC (9: 1a 1: 1 hept-EA) provided the title compound as an orange solid. TLC: rf (1: 1 hept – EA) = 0.27. LC-MS conditions 01: t R = 1.11 min; [M + H] + = 478.01.

2-Chloro-benzyl ester of [2– (2-hydroxymethyl-oxazol-4-ylmethyl) -2H- [1,2,3] triazole-4-yl] -carbamic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-chlorobenzyl ester of {2– [2– (tert-butyl-dimethyl-silanyloxymethyl) –oxazole –4– ilmethyl] –2H– [1,2,3] triazol-4-yl} -carbamic (144 mg, 0.30 mmol) in dry THF (3.0 ml) was treated at 0 ° C with TBAF ( 0.46 ml of a 1M solution in THF, 0.46 mmol). The reaction mixture was stirred at 0 ° C for 30 min. Saturated aqueous NH4Cl (5 ml) was added, the layers were separated and the aqueous layer was extracted with EA (3 x 10 ml). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. Purification of the residue with FC (EA) provided the title compound as a yellow oil. TLC: rf (EA) = 0.25. LC-MS conditions 01: t R = 0.82 min; [M + H] + = 363.90,

2-Chloro-benzyl ester of [2– (2-dihydroxymethyl-oxazol-4-ylmethyl) –2H– [1,2,3] triazol-4-yl] -carbamic acid

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-chloro-benzyl ester of acid [2– (2-hydroxymethyl-oxazol-4-ylmethyl) - 2H– [1,2,3] triazole-4-yl] -carbamic (37 mg, 0.10 mmol) in AcCN (3.0 ml) was treated at room temperature with MnO2 (49 mg, 0.51 mmol) and the The reaction mixture was stirred at room temperature for 16 h before filtering through Celite. The solvent was removed under reduced pressure to provide the title compound as a TLC: rf (EA) = 0.48. LC-MS conditions 02: t R = 0.83 min; [M + H] + = 380.69.

2-Chloro-benzyl ester of {2– [2– (1-hydroxy-ethyl) –oxazol-4-ylmethyl] –2H– [1,2,3] triazol-4-yl} -carbamic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-chloro-benzyl ester of acid [2– (2-dihydroxymethyl-oxazol-4-ylmethyl) - 2H– [1,2,3] triazol-4-yl] -carbamic (19 mg, 0.05 mmol) in THF (1.0 ml) was treated at –65 ° C with methyl magnesium bromide (0, 15 ml of a 1M solution in THF, 0.15 mmol). The reaction mixture was then stirred at -65 ° C for 1 h. The reaction mixture was then slowly heated to room temperature and stirred at this temperature for 45 min. Then saturated aqueous NH4Cl was added and the aqueous layer was extracted with EA (3 x 10 ml). The combined organic extracts were dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. The residue was purified with FC (EA) to provide the title compound as a yellow oil. TLC: rf (EA) = 0.30, Conditions LC – MS 02: tR = 0.89 min, [M + H] + = 378.30,

5– (3-Methoxy-phenyl) -2-methyl-oxazol-4-carboxylic acid:

Prepared from 3– (3-methoxy-phenyl) -3-oxo-propionic acid ethyl ester consecutively following the general procedures F, G and E. Conditions LC-MS 02: tR = 0.82 min; [M + H] + = 234.10,

5– (3,5-Dimethyl-phenyl) -2-methyl-oxazol-4-carboxylic acid:

Prepared from 3– (3,5-dimethyl-phenyl) -3-oxo-propionic acid ethyl ester consecutively following the general procedures F, G and E. Conditions LC-MS 02: tR = 0.89 min; [M + H] + = 232.12

5– (3-Fluoro-phenyl) -2-methyl-oxazol-4-carboxylic acid:

Prepared from 3– (3-fluorophenyl) -3-oxo-propionic acid ethyl ester consecutively following the general procedures F, G and E. Conditions LC-MS 02: tR = 0.83 min; [M + H] + = 222.14.

2-methyl-5-m-tolyl-oxazol-4-carboxylic acid:

Prepared from 3-oxo-3-m-tolyl-propionic acid ethyl ester consecutively following the general procedures F, G and E. Conditions LC-MS 02: t R = 0.85 min; [M + H] + = 218.46.

5– (3-Chloro-phenyl) -2-methyl-oxazol-4-carboxylic acid:

Prepared from 3-chloro-benzoic acid following consecutively the general procedures K, F, G and

E. Conditions LC-MS 02: t R = 0.87 min; [M + H] + = 238.06. 2-methyl-5-phenyl-oxazol-4-carboxylic acid:

Prepared from 3-oxo-3-phenyl-propionic acid ethyl ester, consecutively following the general procedures F, G and E. Conditions LC-MS 02: t R = 0.76 min; [M + H] + = 204.03.

2-methyl-5– (3-trifluoromethyl-phenyl) -oxazole-4-carboxylic acid:

Prepared from 3-trifluoromethyl-benzoic acid consecutively following the general procedures K, F, G and E. Conditions LC-MS 02: t R = 0.91 min; [M + H] + = 272.05.

2-methyl-5– (3-trifluoromethoxy-phenyl) -oxazole-4-carboxylic acid:

Prepared from 3-trifluoromethoxy-benzoic acid consecutively following the general procedures K, F, G and E. Conditions LC-MS 02: t R = 0.93 min; [M + H] + = 288.06.

2-methyl-5-o-tolyl-oxazol-4-carboxylic acid:

Prepared from 3-oxo-3-o-tolyl-propionic acid ethyl ester consecutively following the general procedures F, G and E. LC-MS conditions 02: t R = 0.83 min; [M + H] + = 218.16.

5– (3-Trifluoromethyl-phenyl) -oxazol-4-carboxylic acid:

Prepared from 3-trifluoromethyl-benzoic acid consecutively following the general procedures K, J, I, H and E. Conditions LC-MS 02: t R = 0.89 min; [M + AcCN + H] + = 298.92. 5– (4-Chloro-phenyl) -oxazol-4-carboxylic acid: Prepared from 4-chloro-benzoic acid following consecutively the general procedures K, J, I, H and

E. Conditions LC-MS 02: t R = 0.85 min; [M + AcCN + H] + = 264.87. 5– (3-Trifluoromethoxy-phenyl) -oxazol-4-carboxylic acid: Prepared from 3-trifluoromethoxy-benzoic acid consecutively following the general procedures K,

J, I, H and E. Conditions LC-MS 02: t R = 0.91 min; [M + AcCN + H] + = 314.98.

5– (3-Methoxy-4-methyl-phenyl) -oxazol-4-carboxylic acid:

Prepared from 3-methoxy-4-methyl-benzoic acid following consecutively the general procedures K, J, I, H and E. Conditions LC-MS 02: t R = 0.86 min; [M + H] + = 234.11.

5– (4 – Fluorophenyl) –oxazole – 4-carboxylic acid: Prepared from 4-fluor-benzoic acid following consecutively the general procedures K, J, I, H and

E. Conditions LC-MS 02: t R = 0.80 min; [M + AcCN + H] + = 249.04. 5-m-tolyl-oxazol-4-carboxylic acid:

Prepared from 3-oxo-3-m-tolyl-propionic acid ethyl ester consecutively following the general procedures J, I, H and E. Conditions LC-MS 02: t R = 0.83 min; [M + H] + = 204.17.

5– (3-Methoxy-phenyl) -oxazol-4-carboxylic acid:

Prepared from 3– (3-methoxy-phenyl) -3-oxo-propionic acid ethyl ester consecutively following the general procedures J, I, H and E. Conditions LC-MS 02: t R = 0.80 min; [M + H] + = 220.13.

2-Ethyl-5-phenyl-oxazol-4-carboxylic acid:

Prepared from 3-oxo-3-phenyl-propionic acid ethyl ester consecutively following the general procedures J, I, H and E. Conditions LC-MS 02: t R = 0.85 min; [M + H] + = 218.19.

2-Cyclopropyl-5-phenyl-oxazol-4-carboxylic acid:

Prepared from 3-oxo-3-phenyl-propionic acid ethyl ester consecutively following the general procedures J, I, H and E. Conditions LC-MS 02: t R = 0.87 min; [M + H] + = 230.17. 5– (3 – Fluorophenyl) –oxazole – 4-carboxylic acid: Prepared from 3-fluor-benzoic acid following consecutively the general procedures K, J, I, H and

E. Conditions LC-MS 02: t R = 0.80 min; [M + AcCN + H] + = 249.09.

5– (3-Chloro-phenyl) -oxazole-4-carboxylic acid:

Prepared from 3-chloro-benzoic acid following consecutively the general procedures K, J, I, H and

E. Conditions LC-MS 02: t R = 0.85 min; [M + AcCN + H] + = 265.23. 5– (3-Dimethylamino-phenyl) -oxazol-4-carboxylic acid: Prepared from 3-dimethylamino-benzoic acid, consecutively following the general procedures M

and E. Conditions LC-MS 02: t R = 0.60 min; [M + H] + = 233.36. 5– [3– (2-Hydroxy-ethyl) -phenyl] -oxazol-4-carboxylic acid:

Prepared from 3– (2-hydroxy-ethyl) -benzoic acid consecutively following the general procedures M and E. Conditions LC-MS 02: t R = 0.71 min; [M + H] + = 234.36.

5– [3– (2-Methoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid:

Prepared from 5– [3– (2-methoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid methyl ester following the general procedure E. Conditions LC-MS 02: t R = 0.81 min; [M + H] + = 248.37.

2-methyl-5-m-tolyl-thiazole-4-carboxylic acid:

Prepared from 3-methyl-benzaldehyde following consecutively the general procedures R, S and E. Conditions LC-MS 01: tR = 0.83 min; [M + H] + = 234.01.

5– [3– (2-Isopropoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid:

Prepared from 5– [3– (2-isopropoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid isopropyl ester following the general procedure E. Conditions LC-MS 02: t R = 0.89 min; [M + H] + = 275.6. 5– (3 – Fluorophenyl) –thiazole – 4-carboxylic acid: Prepared from 3-fluor-benzaldehyde following consecutively the general procedures R, T, U, V and

E. Conditions LC-MS 01: t R = 0.81 min; [M + H] + = 224.38. 2-Methoxymethyl-5-phenyl-oxazol-4-carboxylic acid: Prepared from DL-3-Phenylserine Hydrate consecutively following the general procedures W, X

with methoxyacetic acid, Y and Z. Conditions LC-MS 02: t R = 0.81 min; [M + H] + = 234.45.

2– (2-Methoxy-ethyl) -5-phenyl-oxazol-4-carboxylic acid:

Prepared from DL-3-phenylserine hydrate following consecutively the general procedures W, X with 3-methoxy-propionic acid, Y and Z. Conditions LC-MS 01: t R = 0.77 min; [M + H] + = 247.96.

2-Butyl-5-phenyl-oxazol-4-carboxylic acid:

Prepared from DL-3-phenylserine hydrate, consecutively following the general procedures W, X with pentanoic acid, Y and Z. Conditions LC-MS 02: t R = 0.95 min; [M + H] + = 246.45.

2-Isopropyl-5-phenyl-oxazol-4-carboxylic acid:

Prepared from DL-3-phenylserine Hydrate consecutively following the general procedure W, X with isobutyric acid, Y and Z. Conditions LC-MS 02: t R = 0.90 min; [M + H] + = 232.51.

2-Benzyl-5-phenyl-oxazol-4-carboxylic acid:

Prepared from DL-3-phenylserine hydrate following consecutively the general procedures W, X with phenyl-acetic acid, Y and Z. Conditions LC-MS 02: t R = 0.95 min; [M + H] + = 220.18.

2– (2-tert-Butoxycarbonylethyl) -5-phenyl-oxazol-4-carboxylic acid:

Prepared from DL-3-phenylserine hydrate following consecutively the general procedures W, X with mono-tert-butyl ester of succinic acid, Y and Z. Conditions LC-MS 02: t R = 0.95 min; [M + H] + = 318.32.

5– (6-Trifluoromethyl-pyridin-2-yl) -oxazol-4-carboxylic acid lithium salt:

Prepared from 6-trifluoromethyl-pyridine-2-carboxylic acid consecutively following the general procedures M and E (using LiOH). LC-MS conditions 02: t R = 0.80 min; [M + H] + = 259.12.

Preparation of Examples

Example 1: 2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by any of B or C, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ylmethyl] –2H– [1, 2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 0.99 min; [M + H] + = 377.99.

Example 2: (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide: Following the general procedure A followed by any of B or C, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2–

il) –furan – 2-ylmethyl] –2H– [1,2,3] triazol-4-ylamine and (E) –3– (4-trifluoromethyl-phenyl) -acrylic acid. LC-MS conditions 02: t R = 1.03 min; [M + H] + = 404.99.

Example 3:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-phenyl) –2-methyl-oxazole– 4– carboxylic:

Following the general procedure A followed by any of B or C, from 2– [5– (2-methyl– [1,3] ddioxolan – 2– il) –furan – 2-ilmethyl] –2H– [1, 2,3] triazol-4-ylamine and 5– (3-methoxy-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 1.03 min; [M + H] + = 421.98.

Example 4: 2-Chloro-benzyl ester of [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazole-4-yl] -carbamic acid:

Following the general procedure D followed by any of B or C, from 2– [5– (2-methyl– [1,3] ddioxolan – 2– il) –furan – 2-ilmethyl] –2H– [1, 2,3] triazol-4-ylamine and (2-chloro-phenyl) -methanol.

LC-MS conditions 02: t R = 1.00 min; [M + H] + = 374.97.

Example 5: [2– (5 – oxo-hexyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-phenyl-oxazol-4-carboxylic acid: Following the general procedure A followed by B, from 2– [4– (2 – methyl– [1,3] ddioxolan – 2 – il) –butyl] –2H–

[1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 0.99 min; [M + H] + = 354.36.

Example 6: (E) –N– [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-chloro-phenyl) -acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazole-4-ylamine and (E) -3– (4-chloro-phenyl) -acrylic acid. LC-MS 05b conditions: t R = 0.7 min; [M + H] + = 371.11.

Example 7: (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-trifluoromethyl-phenyl) -acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (2-trifluoromethyl-phenyl) -acrylic acid. LC-MS 05b conditions: t R = 0.71 min; [M + H] + = 405.19.

Example 8: (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) -acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (3-trifluoromethoxy-phenyl) -acrylic acid. LC-MS 05b conditions: t R = 0.74 min; [M + H] + = 421.12.

Example 9: (E) –N– [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3 – or – tolyl-acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazole-4-ylamine and acid (E) -3-o-tolyl-acrylic. LC-MS 05b conditions: t R = 0.67 min; [M + H] + = 351.18.

Example 10: (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-chloro-4-fluor-phenyl) –Acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazole-4-ylamine and (E) -3– (2-chloro-4-fluorophenyl) -acrylic acid. LC-MS 05b conditions: t R = 0.7 min; [M + H] + = 389.14.

Example 11: (E) –N– [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3-m-tolyl-acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazole-4-ylamine and acid (E) -3-m-tolyl-acrylic. LC-MS 05b conditions: t R = 0.68 min; [M + H] + = 351.22.

Example 12: (E) –N– [2– (5 – Acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3-p-tolyl-acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazole-4-ylamine and acid (E) -3-p-tolyl-acrylic. LC-MS 05b conditions: t R = 0.68 min; [M + H] + = 351.22.

Example 13: (E) –N– [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-methoxy-phenyl) -acrylamide: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (4-methoxy-phenyl) -acrylic acid. LC-MS 05b conditions: t R = 0.62 min; [M + H] + = 367.18.

Example 14:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3,5-dimethyl-phenyl) –2 – methyl– oxazol – 4– carboxylic:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3,5-dimethyl-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.83 min; [M + H] + = 420.21.

Example 15:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethyl-phenyl) –oxazole-4– carboxylic acid:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-trifluoromethyl-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.77 min; [M + H] + = 446.17.

Example 16:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2-methyl-oxazole– 4– carboxylic:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5- (3-fluorophenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.75 min; [M + H] + = 410.17.

Example 17: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (4-chloro-phenyl) –oxazol – 4 –Carboxylic:

Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (4-chloro-phenyl) -oxazol-4-carboxylic acid. LC-MS 05b conditions: t R = 0.76 min; [M + H] + = 412.13.

Example 18: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazole-4-ylamine and 5– (m-tolyl) -2-methyl-oxazol-4-carboxylic acid LC-MS 05b conditions: t R = 0.78 min; [M + H] + = 406.18.

Example 19:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-trifluoromethoxy-phenyl) –oxazol-4– carboxylic acid:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-trifluoromethoxy-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.79 min; [M + H] + = 462.1.

Example 20:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2 – methyl-oxazole– 4– carboxylic:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-chloro-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.80 min; [M + H] + = 426.14.

Example 21:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-4-methyl-phenyl) –oxazole– 4- carboxylic: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5– (3-methoxy-4-methyl-phenyl) -oxazol-4-carboxylic acid. LC-MS 05b conditions: t R = 0.77 min; [M + H] + = 422.19.

Example 22: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (4-fluorophenyl) –oxazole-4-carboxylic acid: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5– (4-fluorophenyl) -oxazol-4-carboxylic acid Conditions LC-MS 05b: t R = 0.70 min; [M + H] + = 396.18.

Example 23: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-m-tolyl-oxazol-4-carboxylic acid: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5– (m-tolyl) -oxazol-4-carboxylic acid. LC-MS 05b conditions: t R = 0.73 min; [M + H] + = 392.19.

Example 24: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-phenyl) -oxazole-4-carboxylic acid: Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5– (3-methoxy-phenyl) -oxazol-4-carboxylic acid. LC-MS 05b conditions: t R = 0.69 min; [M + H] + = 408.22.

Example 25:

[2– (5-Acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5-phenyl-oxazol-4– carboxylic acid:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-phenyl-2-methyl-oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.73 min; [M + H] + = 392.18.

Example 26:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole acid– 4-carboxylic:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-trifluoromethyl-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.81 min; [M + H] + = 460.16.

Example 27:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) - oxazole acid– 4-carboxylic:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-trifluoromethoxy-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.83 min; [M + H] + = 476.12.

Example 28: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5 – o-tolyl-oxazol-4 acid –Carboxylic:

Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazole-4-ylamine and 5– (o-tolyl) -2-methyl-oxazol-4-carboxylic acid LC-MS 05b conditions: t R = 0.72 min; [M + H] + = 406.2.

Example 29: [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-ethyl-5-phenyl-oxazol-4-carboxylic acid :

Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-ethyl-5-phenyl-oxazol-4-carboxylic acid. LC-MS 05b conditions: t R = 0.80min; [M + H] + = 406.19.

Example 30:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-cyclopropyl-5-phenyl-oxazol-4– carboxylic acid:

Following the general procedure A followed by L, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-cyclopropyl-5-phenyl-oxazol-4-carboxylic acid.

LC-MS 05b conditions: t R = 0.81min; [M + H] + = 417.69.

Example 31: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3 – Fluor-phenyl) –oxazol – 4 –Carboxylic:

Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-fluorophenyl) -oxazol-4-carboxylic acid. LC-MS 05b conditions: t R = 0.71 min; [M + H] + = 396.19.

Example 32: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-Chloro-phenyl) –oxazol – 4 –Carboxylic:

Following the general procedure A followed by L, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-chloro-phenyl) -oxazol-4-carboxylic acid. LC-MS 02b conditions: t R = 1.04 min; [M + H] + = 411.88.

Example 33: [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –thiophe – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.03 min; [M + H] + = 394.18.

Example 34: [2– (3-Acetyl-benzyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-phenyl-oxazol-4-carboxylic acid: Following the general procedure A followed by B, from 2– [3– (2-methyl– [1,3] ddioxolan – 2-yl) –benzyl] –2H–

[1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.04 min; [M + H] + = 388.29.

Example 35: 2-Chloro-benzyl ester of [2– (3-acetyl-benzyl) -2H– [1,2,3] triazol-4-yl] -carbamic acid: Following the general procedure D (step 2) followed by B, from 2– [3– (2-methyl– [1,3] ddioxolan – 2-il) -

benzyl] –2H– [1,2,3] triazole-4-ylamine and 2-chlorobenzyl chloroformate. LC-MS conditions 01: t R = 1.00 min; [M + H] + = 384.95.

Example 36:

5-Phenyl-oxazol-4-carboxylic [2– (5,5-difluor-hexyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazole-4-carboxylic acid :

Following general procedure A, from 2– (5,5-difluor-hexyl) –2H– [1,2,3] triazole-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 1.09 min; [M + H] + = 376.26.

Example 37: [2– (5-methanesulfonyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-phenyl-oxazol-4-carboxylic acid: Following general procedure A, from 2– (5-methanesulfonyl-furan-2-ylmethyl) –2H– [1,2,3] triazole-4-ylamine and

5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 0.97 min; [M + H] + = 413.84.

Example 38:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-dimethylamino-phenyl) –oxazole-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-dimethylamino-phenyl) -oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 0.84 min; [M + H] + = 421.37.

Example 39: [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-phenyl-oxazol-4-carboxylic acid: Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 0.98 min; [M + H] + = 395.0,

Example 40: 2-Chloro-benzyl ester of 2- (4-acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazole-4-yl] -carbamic acid: Following the general procedure D (step 2) followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazole–

2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine and 2-chlorobenzyl-chloroformate. LC-MS conditions 02: t R = 0.99 min; [M + H] + = 391.9.

Example 41: [2– (4-Acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazole-4-yl] -carbamic acid 2-Chlorobenzyl ester Following the general procedure D (step 2) followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –pyridin–

2-ylmethyl] –2H– [1,2,3] triazole-4-ylamine and 2-chlorobenzyl-chloroformate. LC-MS conditions 02: t R = 0.99 min; [M + H] + = 386.3.

Example 42:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– [3– (2-methoxy-ethyl) -phenyl] - oxazol – 4– carboxylic:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– [3– (2-methoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 1.00 min; [M + H2O + H] + = 454.30,

Example 43: [2– (6-Acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [6– (2 – methyl– [1,3] ddioxolan – 2 – il) –pyridin – 2– ilmethyl] –2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 01: t R = 0.98 min; [M + H] + = 388.95.

Example 44:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-methoxymethyl-phenyl) –oxazole-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-methoxymethyl-phenyl) -oxazol-4-carboxylic acid.

LC-MS conditions 01: t R = 0.94 min; [M + H] + = 421.95.

Example 45: [2– (2-Acetyl-thiazol-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-4-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.01 min; [M + H] + = 394.81.

Example 46: [2– (4-Acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by N, from 2– [4– (2 – methyl– [1,3] ddioxolan – 2 – il) –pyridin – 2– ilmethyl] –2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 01: t R = 0.93 min; [M + H] + = 388.95.

Example 47: [2– (2-Acetyl-pyridin-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [2– (2 – methyl– [1,3] ddioxolan – 2 – il) –pyridin – 4– ilmethyl] –2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.01 min; [M + H] + = 389.64.

Example 48: Chloro-benzyl ester of [2– (2-acetyl-pyridin-4-ylmethyl) –2H– [1,2,3] triazol-4-yl] -carbamic acid: Following the general procedure D (step 2) followed by B, from 2– [2– (2-methyl– [1,3] ddioxolan – 2-il) –pyridin–

4-ylmethyl] –2H– [1,2,3] triazole-4-ylamine and 2-chlorobenzyl-chloroformate. LC-MS conditions 01: t R = 0.97 min; [M + H] + = 385.93.

Example 49: [2– (5-acetyl-thiophene-3-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophe-3-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.03 min; [M + H] + = 394.0,

Example 50: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5-m-tolyl-thiazole-4 acid –Carboxylic:

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid. LC-MS conditions 02: t R = 1.06 min; [M + H] + = 422.18.

Example 51: [2– (3-Acetyl-isoxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by L (with a reaction time of 3 weeks), from 2– [3– (2– methyl– [1,3] ddioxolan – 2-yl) –isoxazol – 5-ylmethyl] –2H– [1,2,3] triazole-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.01 min; [M + H] + = 379.2.

Example 52:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-isopropoxymethyl-phenyl) –oxazole-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-isopropoxymethyl-phenyl) -oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 1.04 min; [M + H2O + H] + = 467.82.

Example 53:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– [3– (2-Isopropoxy-ethyl) -phenyl] - oxazol– 4-carboxylic:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– [3– (2-isopropoxy-ethyl) -phenyl] -oxazol-4-carboxylic acid

LC-MS conditions 02: t R = 1.05 min; [M + H2O + H] + = 481.98.

Example 54:

[2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazole-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.99 min; [M + H] + = 422.13.

Example 55:

[2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2 – methyl-oxazole– 4– carboxylic:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-chloro-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 1.01 min; [M + H] + = 442.03.

Example 56: [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-m-tolyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –thiophe – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-m-tolyl-oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.94 min; [M + H] + = 408.12.

Example 57: [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-phenyl-oxazol-4-carboxylic acid :

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –thiophe – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5-phenyl-oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.94 min; [M + H] + = 408.12.

Example 58:

[2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole acid– 4-carboxylic:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5- (3-trifluoromethyl-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 1.02 min; [M + H] + = 476.0,

Example 59: [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluor-phenyl) –oxazol – 4 –Carboxylic:

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –thiophe – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-fluorophenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.91 min; [M + H] + = 412.05.

Example 60:

[2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-dimethylamino-phenyl) –oxazol-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-dimethylamino-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.78 min; [M + H] + = 436.98.

Example 61: [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –oxazol – 4 –Carboxylic:

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –thiophe – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-chloro-phenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.96 min; [M + H] + = 427.95.

Example 62:

2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) - oxazole-4 –Carboxylic:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5- (3-trifluoromethoxy-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 1.04 min; [M + H] + = 492.01.

Example 63: [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (4-fluorophenyl) -oxazole-4-carboxylic acid: Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –thiophe – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5– (4-fluorophenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.91 min; [M + H] + = 412.01.

Example 64:

[2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazole-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-trifluoromethoxy-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.99 min; [M + H] + = 478.0,

Example 65:

[2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-methoxy-phenyl) –oxazole-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiophene-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-methoxy-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.9 min; [M + H] + = 424.07.

Example 66: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluor-phenyl) –thiazole – 4 –Carboxylic:

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-fluorophenyl) -thiazole-4-carboxylic acid. LC-MS conditions 02: t R = 1.00 min; [M + H] + = 411.85.

Example 67: [2– (2-Acetyl-thiazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-5-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 01: t R = 0.98 min; [M + H] + = 394.94.

Example 68: 2-Chloro-benzyl ester of [2– (2-acetyl-thiazol-5-ylmethyl) -2H– [1,2,3] triazole-4-yl] -carbamic acid: Following the general procedure D followed by B, from 2– [2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 5-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and (2-chloro-phenyl) -methanol. LC-MS conditions 01: t R = 0.98 min; [M + H] + = 391.9.

Example 69: (E) –N– [2– (2-acetyl-thiazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide: Following the general procedure A followed by B, from 2– [2– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-5-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (4-trifluoromethyl-phenyl) -acrylic acid. LC-MS conditions 01: t R = 1.02 min; [M + H] + = 421.90,

Example 70: [2– (2-Acetyl-oxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of {2– [2– (1-hydroxy-ethyl) –oxazol – 5-ilmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 5-phenyl-oxazol-4-carboxylic acid (60 mg, 0.16 mmol) in AcCN (1.6 ml) was treated at room temperature with MnO2 (114 mg, 1.18 mmol) and the reaction mixture was stirred at room temperature overnight before being filtered through Celite. The solvent was removed under reduced pressure and the residue was dissolved in EA (10 ml), washed with water (10 ml), and brine. The organic layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a white foam. LC-MS conditions 02: t R = 0.97 min; [M + H] + = 379.06.

Example 71: 2-Chloro-benzyl ester of [2– (5-acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazole-4-yl] -carbamic acid: Following the general procedure D followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and (2-chloro-phenyl) -methanol. LC-MS conditions 01: t R = 0.96 min; [M + H] + = 391.92.

Example 72: [2– (4-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [4– (2 – methyl– [1,3] ddioxolan – 2 – il) –thiophe – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 01: t R = 0.99 min; [M + H] + = 393.92.

Example 73: [2– (5-acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 0.99 min; [M + H] + = 394.94.

Example 74: (E) –N– [2– (5-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide: Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (4-trifluoromethyl-phenyl) -acrylic acid. LC-MS conditions 02: t R = 1.03 min; [M + H] + = 421.89.

Example 75:

[2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5-m-tolyl-oxazole-4– acid carboxylic:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.95 min; [M + H] + = 423.12.

Example 76:

[2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2-methyl-oxazole– 4– carboxylic:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-chloro-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.98 min; [M + H] + = 442.98.

Example 77: [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-phenyl-oxazol-4-carboxylic acid :

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5-phenyl-oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.90 min; [M + H] + = 409.04.

Example 78:

[2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole acid– 4-carboxylic:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methyl-5- (3-trifluoromethyl-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.98 min; [M + H] + = 477.16.

Example 79: [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluor-phenyl) –oxazol – 4 –Carboxylic:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-fluorophenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.86 min; [M + H] + = 413.12.

Example 80:

[2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-dimethylamino-phenyl) –oxazol-4– carboxylic acid: Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5– (3-dimethylamino-phenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.71 min; [M + H] + = 438.13.

Example 81: [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –oxazol – 4 –Carboxylic:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-chloro-phenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.92 min; [M + H] + = 429.02.

Example 82:

[2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) - oxazol-4-carboxylic: Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and 2-methyl-5– (3-trifluoromethoxy-phenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 1.00 min; [M + H] + = 492.95.

Example 83: [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (4-fluorophenyl) –oxazole-4-carboxylic acid: Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and 5– (4-fluorophenyl) -oxazol-4-carboxylic acid. LC-MS 05 conditions: t R = 0.86 min; [M + H] + = 413.09.

Example 84:

[2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazol-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-trifluoromethoxy-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.95 min; [M + H] + = 479.04.

Example 85:

[2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-methoxy-phenyl) –oxazol-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-methoxy-phenyl) -oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.85 min; [M + H] + = 425.02.

Example 86: (E) –N– [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide: Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (4-trifluoromethyl-phenyl) -acrylic acid. LC-MS 05 conditions: t R = 0.88 min; [M + H] + = 422.04.

Example 87: (E) –N– [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) -acrylamide: Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (3-trifluoromethoxy-phenyl) -acrylic acid. LC-MS 05 conditions: t R = 0.90 min; [M + H] + = 438.02.

Example 88:

[2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-phenyl) –2-methyl-oxazole– 4– carboxylic:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-methoxy-phenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.90 min; [M + H] + = 439.04.

Example 89:

[2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2 – methyl-oxazole– 4– carboxylic:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol-2-ylmethyl] - 2H– [1,2,3] triazol-4-ylamine and 5– (3-fluorophenyl) -2-methyl-oxazol-4-carboxylic acid.

LC-MS 05 conditions: t R = 0.92 min; [M + H] + = 427.00,

Example 90: [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol– 2-ylmethyl] –2H– [1,2,3] triazol-4-ylamine and 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid. LC-MS 05 conditions: t R = 0.96 min; [M + H] + = 438.97.

Example 91: [2– (4-acetyl-oxazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid:

Following general procedure A, from 1– [2– (4-amino– [1,2,3] triazol-2-ylmethyl) -oxazol-4-yl] -ethanone and 5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 0.94 min; [M + H] + = 379.22.

Example 92:

[2– (5-Acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methoxymethyl-5-phenyl-oxazol-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-methoxymethyl-5-phenyl-oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 1.00 min; [M + H] + = 422.0,

Example 93:

[2– (5-Acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methoxymethyl-5-phenyl-oxazol-4– carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2- (2-methoxy-ethyl) -5-phenyl-oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 1.02 min; [M + H] + = 436.08.

Example 94:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-butyl-5-phenyl-oxazol-4-carboxylic acid:

Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2-butyl-5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.13 min; [M + H] + = 433.99.

Example 95:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-isopropyl-5-phenyl-oxazol-4– carboxylic: Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and 2-isopropyl-5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.10 min; [M + H] + = 420.42.

Example 96: (E) –N– [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-trifluoromethyl-phenyl) -acrylamide: Following the general procedure A followed by B, from 2– [4– (2-methyl– [1,3] ddioxolan – 2-yl) –thiazol – 2-ylmethyl] -

2H– [1,2,3] triazol-4-ylamine and (E) -3– (2-trifluoromethyl-phenyl) -acrylic acid. LC-MS 05 conditions: t R = 0.87 min; [M + H] + = 422.02.

Example 97: [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-benzyl-5-phenyl-oxazol-4-carboxylic acid: Following the general procedure A followed by B, from 2– [5– (2 – methyl– [1,3] ddioxolan – 2 – il) –furan – 2 – ilmethyl] -

2H– [1,2,3] triazol-4-ylamine and 2-benzyl-5-phenyl-oxazol-4-carboxylic acid. LC-MS conditions 02: t R = 1.11 min; [M + H] + = 468.06.

Example 98:

3– {4– [2– (5-Acetyl-furan-2-ylmethyl) -2H– [1,2,3] triazole-4-ylcarbamoyl] -5-phenyl-oxazol-2– tert-butyl acid ester il} -propionic:

Following the general procedure A followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2-ilmethyl] - 2H– [1,2,3] triazol-4-ylamine and 2– (2-tert-butoxycarbonylethyl) -5-phenyl-oxazol-4-carboxylic acid.

LC-MS conditions 02: t R = 1.12 min; [M + H] + = 506.00,

Example 99:

[2– (2-acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2 – methyl-oxazole– 4– carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of {2– [2– (1-hydroxy-ethyl) –oxazol – 5-ilmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 5– (3-fluorophenyl) -2-methyl-oxazol-4-carboxylic acid (49 mg, 0.12 mmol) in AcCN (2, 0 ml) was treated at room temperature with MnO2 (86 mg, 0.89 mmol) and the reaction mixture was stirred at room temperature overnight before being filtered through Celite. The solvent was removed under reduced pressure and the residue was dissolved in EA (10 ml), washed with water (10 ml), and brine. The organic layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow solid. LC-MS conditions 02: t R = 1.03 min; [M + H] + = 410.85.

Example 100:

[2– (2-Acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of {2– [2– (1-hydroxy-ethyl) –oxazol – 5-ilmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid (60 mg, 0.15 mmol) in AcCN (2.0 ml) is treated at room temperature with MnO2 (107 mg, 1.11 mmol) and the reaction mixture was stirred at room temperature overnight before being filtered through Celite. The solvent was removed under reduced pressure and the residue was dissolved in EA (10 ml), washed with water (10 ml), and brine. The organic layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a yellow solid. LC-MS conditions 02: t R = 1.04 min; [M + H] + = 407.07.

Example 101:

[2– (2-acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2-methyl-oxazole– 4– carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2– [2– (1-hydroxy-ethyl) –oxazol – 5-ylmethyl] –2H– [ 1,2,3] triazol-4-yl} -amide of 5– (3-chloro-phenyl) -2-methyl-oxazol-4-carboxylic acid (54 mg, 0.13 mmol) in AcCN (1.5 ml) was treated at room temperature with MnO2 (91 mg, 0.94 mmol) and the reaction mixture was stirred at room temperature overnight before being filtered through Celite. The solvent was removed under reduced pressure and the residue was dissolved in EA (10 ml), washed with water (10 ml), and brine. The organic layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a white solid. LC-MS conditions 02: t R = 1.06 min; [M + H] + = 426.75.

Example 102:

[2– (2-Acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-m-tolyl-oxazol-4-carboxylic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of {2– [2– (1-hydroxy-ethyl) –oxazol – 5-ilmethyl] –2H– [1,2,3] triazol-4-yl} -amide of 5-m-tolyl-oxazol-4-carboxylic acid (44 mg, 0.11 mmol) in AcCN (1.5 ml) was treated at room temperature with MnO2 (81 mg, 0.84 mmol) and the reaction mixture was stirred at room temperature overnight before being filtered through Celite. The solvent was removed under reduced pressure and the residue was dissolved in EA (10 ml), washed with water (10 ml), and brine. The organic layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a white solid. LC-MS conditions 02: t R = 1.01 min; [M + H] + = 392.97.

Example 103:

[2– (2-Acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) - oxazole acid– 4-carboxylic:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of {2– [2– (1-hydroxy-ethyl) –oxazol – 5-ilmethyl] –2H– [1,2,3] triazol-4-yl} –amide of 2-methyl– 5– (3-trifluoromethoxy-phenyl) –oxazol-4-carboxylic acid (54 mg, 0.11 mmol) in AcCN (1, 5 ml) was treated at room temperature with MnO2 (85 mg, 0.85 mmol) and the reaction mixture was stirred at room temperature overnight before filtering through Celite. The solvent was removed under reduced pressure and the residue was dissolved in EA (10 ml), washed with water (10 ml), and brine. The organic layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure to provide the title compound as a white solid. LC-MS conditions 02: t R = 1.09 min; [M + H] + = 476.95.

Example 104:

2-Chloro-benzyl ester of [2– (2-acetyl-oxazol-4-ylmethyl) -2H- [1,2,3] triazole-4-yl] -carbamic acid:

In a flame-dried round bottom flask, equipped with a magnetic stir bar and under an inert atmosphere (N2), a solution of 2-chloro-benzyl ester of acid {2– [2– (1-hydroxy-ethyl) –oxazole –4 – ilmethyl] –2H– [1,2,3] triazol-4-yl} -carbamic (10 mg, 0.03 mmol) in AcCN (5.0 ml) was treated at room temperature with MnO2 (13 mg, 0 , 13 mmol) and the reaction mixture was stirred at 50 ° C for 2 h before filtering through Cel ite. TLC: rf (EA) = 0.60, Conditions LC-MS 02: tR = 0.97 min; [M + H] + = 376.04.

Example 105:

[2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (6-trifluoromethyl-pyridin-2-yl) –oxazole– 4-carboxylic:

Following the general procedure Z1 followed by B, from 2– [5– (2-methyl– [1,3] ddioxolan – 2-yl) –furan – 2– ilmethyl] –2H– [1,2,3] triazol-4-ylamine and lithium salt of 5– (6-trifluoromethyl-pyridin-2-yl) -oxazol-4-carboxylic acid.

LC-MS conditions 01: t R = 0.91 min; [M + H] + = 446.99.

II Biological Tests

In vitro test

The agonistic activity of the ALX receptor of the compounds of formula (I) is determined according to the following experimental procedure.

Experimental procedure:

Intracellular calcium measurements:

Cells expressing the recombinant human receptor ALX and Gα (HEK293-hALXR-Gα16) were cultured to 80% confluence in a Culture Medium (GM). The cells were detached from the culture plates with a cell dissociation buffer (Invitrogen, 13151-014), and harvested by centrifugation at 1000 rpm at room temperature for 5 min in Test Buffer (AB) (equal parts) from Hank's BSS (Gibco, 14065–049) and DMEM without Phemol Red (Gibco, 11880–028)). After 60 min. incubation at 37 ° C under 5% CO 2 in AB

supplemented with 1 µM of Fluo – 4 (AM) (TEFLABS.COM, 0152), 0.04% (v / v) Pluronic F – 127 (Molecular Probes, P6866), and 20 mM HEPES (Gibco, 15630–056) , the cells were washed and resuspended in AB. Then they were seeded on FLIPR test plates of 384 receptacles (Greiner, 781091) at 50,000 cells in 70 µl and sedimented by centrifugation at 1,000 rpm for 1 min. Stock solutions of the test compounds were prepared Stock solutions of the test compounds were prepared, at a concentration of 10 mM in DMSO, and serially diluted in AB at the concentrations required for activation of the response curves at the dose WKYMVm (Phoenix Peptides) was used as a reference agonist. A FLIPR384 instrument (Molecular Devices) was used according to the conventional instructions of the producer, adding 4 µl of test compound dissolved in 10 mM in DMSO and diluted before the experiment in test buffer to obtain the desired final concentration. Fluorescence changes were monitored before and after the addition of test compounds at lex = 488 nm and lem = 540 nm. Peak emission values above the base level, after the addition of compounds, were exported after subtraction of the baseline. The values were normalized to a high level control (compound WKYMVm, 10 nM final concentration) after subtraction of the baseline value (AB addition). The XLlfit 3.0 (IDBS) program was used to adjust the

15 data to a single place on the dose response curve of equation (A + ((B – A) / (1 + ((C / x) ^ D)))) and to calculate EC50 values.

The agonistic activities (EC50 values) of all exemplified compounds are in the range of 0.03–1850 nM with an average of 60 nM with respect to the ALX receptor. The agonistic activities of the selected compounds are shown in Table 1.

20 Table 1

Compound

CE50 [nM]

Example 1: [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5-phenyl-oxazol-4-carboxylic acid

1.8

Example 5: [2– (5-oxo-hexyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid

1.6

Example 8: (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) - acrylamide

1.2

Example 21: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-4-methyl-phenyl) - oxazol-4-carboxylic

53

Example 26: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) acid –Oxazol – 4 – carboxylic

2.0

Example 30: [2– (5-acetyl-furan-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-cyclopropyl-5-phenyl-oxazole-4-carboxylic acid

0.8

Example 33: [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid

2.8

Example 35: 2-Chloro-benzyl ester of [2– (3-acetyl-benzyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid

8.5

Example 36: [2– (5,5-difluor-hexyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid

4.9

Example 37: [2– (5-methanesulfonyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid

24

Example 38: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-dimethylamino-phenyl) - oxazol – 4 –Carboxylic

1.9

(cont.)

Example 40: 2-Chloro-benzyl ester of [2– (4-acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid

1.3

Example 41: 2-Chloro-benzyl ester of [2– (4-acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid

twenty-one

Example 42: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– [3– (2-methoxy-ethyl) - phenyl] - oxazol-4-carboxylic

2.1

Example 43: [2– (6-Acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid

203

Example 49: [2– (5-acetyl-thiophene-3-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid

57

Example 50: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5-m-tolyl-thiazole-4 acid - carboxylic

98

Example 71: 2-Chloro-benzyl ester of [2– (5-acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid

2. 3

Example 91: [2– (4-Acetyl-oxazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid

0.7

Example 93: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 2– (2-methoxy-ethyl) –5-phenyl - oxazol-4-carboxylic

5.2

Example 99: [2– (2-acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluor-phenyl) –2 – methyl - oxazol-4-carboxylic

8.1

Example 104: 2-Chloro-benzyl ester of [2– (2-acetyl-oxazol-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid

1.4

Example 105: [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide acid

36

Claims (17)

1. A compound of the formula (I), H (I) in which A represents a phenyl group - or a heterocyclyl, in which the two substituents are in a 1.3 arrangement; or A represents propan-1,3-diyl; E represents * - C1 – C4 alkyl –O–, –CH = CH– or ; 10 in which the asterisks indicate the link that is linked to R1; Q represents O or S; R3 represents hydrogen, C1-C4 alkyl, cyclopropyl, C1-C4 alkoxy-C1-C4 alkyl, benzyl or -CH2CH2C (O) OtBu; R1 represents a pyridyl group or an aryl group, wherein said group is unsubstituted, mono-, di- or tri-substituted, wherein the substituents are independently selected from the group consisting of halogen, C1-15 C4 alkyl, C1-C4 alkoxy, C1-C4 fluoralkyl, C1-C4 fluoralkoxy, di– [C1-C3 alkyl] -amino and C1 alkoxy C4 C1-C2 alkyl; Y R2 represents -CO-C1-C3 alkyl, -CF2- C1-C3 alkyl, or -SO2 C1-C3 alkyl; or a salt of said compound. 2. A compound of formula (I) according to claim 1, wherein A represents phenyl-1,3-diyl, furan-2,5-diyl, oxazol-2,4-diyl, oxazol-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl, 20 thiazol-2,4-diyl, thiazol-2,5-diyl, pyridin-2,4-diyl, pyridin-2,6-diyl or propan-1,3-diyl; or a salt of said compound. 3. A compound of formula (I) according to any one of claims 1 or 2, wherein A represents furan-2,5-diyl, oxazol-2,4-diyl with R2 attached in position 2, oxazol-2 , 4-diyl with R2 attached in position 4, oxazol-2,5-diyl with R2 attached in position 2, thiophene-2,5-diyl or thiazol-2,4-diyl with R2 attached in position 4; 25 or a salt of said compound. 4. A compound of formula (I) according to any one of claims 1 to 3, wherein A represents furan-2,5-diyl or thiophene-2,5-diyl; or a salt of said compound. 5. A compound of formula (I) according to any one of claims 1 or 2, wherein 30 A represents propan-1,3-diyl; or a salt of said compound. 6. A compound of formula (I) according to any one of claims 1 to 5, wherein E represents * - C1 – C4 – O– or –CH = CH– alkyl, wherein the asterisk indicates the link that is linked to R1; 35 or a salt of said compound. 7. A compound of formula (I) according to any one of claims 1 to 5, wherein E represents , in which the asterisk indicates the link that is linked to R1; or a salt of said compound. 8. A compound of formula (I) according to any one of claims 1 to 5 or 7, wherein R3 represents hydrogen or methyl; or a salt of said compound. 9. A compound of formula (I) according to any of claims 1 to 8, wherein R1 represents phenyl, which is unsubstituted, mono- or di-substituted, in which the substituents are independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl, trifluoromethoxy, and dimethylamino; or a salt of said compound. 10. A compound of formula (I) according to any one of claims 1 to 9, wherein R2 represents -CO-C1-C3 alkyl; or a salt of said compound. 11. A compound of formula (I) according to claim 1, selected from the group consisting of: [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-phenyl) –2-methyl-oxazole– 4- carboxylic; Y 2-Chloro-benzyl ester of [2– (5-acetyl-furan-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; or a salt of said compound. 12. A compound of formula (I) according to claim 1, selected from the group consisting of: [2– (5 – oxo-hexyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-chloro-phenyl) -acrylamide; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-trifluoromethyl-phenyl) -acrylamide; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) -acrylamide; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -3-o-tolyl-acrylamide; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-chloro-4-fluor-phenyl) –Acrylamide; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -3-m-tolyl-acrylamide; (E) –N– [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3-p-tolyl-acrylamide; (E) –N– [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-methoxy-phenyl) -acrylamide; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3,5-dimethyl-phenyl) –2 – methyl– oxazol – 4– carboxylic; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethyl-phenyl) –oxazole-4-carboxylic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2-methyl-oxazole– 4-carboxylic; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (4-chloro-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazole-4-carboxylic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2 – methyl-oxazole– 4-carboxylic; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-4-methyl-phenyl) –oxazole– 4- carboxylic; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (4-fluorophenyl) -oxazole-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-m-tolyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 5– (3-methoxy-phenyl) -oxazole-4-carboxylic acid; 2-methyl-5-phenyl-oxazol-4-carboxylic [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl acid - 5-phenyl-oxazol-4-carboxylic; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole acid– 4- carboxylic; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole acid– 4- carboxylic; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-o-tolyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-ethyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-cyclopropyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-fluorophenyl) –oxazole-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-chloro-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (3-Acetyl-benzyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (3-acetyl-benzyl) -2H– [1,2,3] triazol-4-yl] -carbamic acid; [2– (5,5-difluor-hexyl) –2H– [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-methanesulfonyl-furan-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-dimethylamino-phenyl) -oxazole-4-carboxylic acid; [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazole-4-yl] -carbamic acid, 2-Chloro-benzyl ester of [2– (4-acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– [3– (2-methoxy-ethyl) -phenyl] - oxazol – 4– carboxylic; [2– (6-Acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-methoxymethyl-phenyl) -oxazole-4-carboxylic acid; [2– (2-Acetyl-thiazol-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (4-Acetyl-pyridin-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (2-Acetyl-pyridin-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (2-acetyl-pyridin-4-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; [2– (5-Acetyl-thiophene-3-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; Y [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid; or a salt of said compound. 13. A compound of formula (I) according to claim 1, selected from the group consisting of: [2– (3-acetyl-isoxazol-5-ylmethyl) -2H- [1,2,3] triazole-4 -Yl] -amide of 5-phenyl-oxazol-4-carboxylic acid;

[2– (5 – acetyl – furan – 2 – ylmethyl) –2H– [1,2,3] triazol – 4-yl] –amide

from acid 5– (3-isopropoxymethyl-phenyl) –oxazol – 4–

carboxylic;

[2– (5 – acetyl – furan – 2 – ylmethyl) –2H– [1,2,3] triazol – 4-yl] –amide

from 5– [3– (2-Isopropoxy-ethyl) -phenyl] -oxazol-4– acid

carboxylic; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2 – methyl-oxazole– 4- carboxylic; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-m-tolyl-oxazol-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole acid– 4- carboxylic; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-fluorophenyl) -oxazole-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-dimethylamino-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –oxazol-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole acid– 4- carboxylic; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] –amide of 5– (4-fluorophenyl) -oxazole-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazole-4-carboxylic acid; [2– (5-acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-methoxy-phenyl) -oxazole-4-carboxylic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-fluorophenyl) -thiazole-4-carboxylic acid; [2– (2-Acetyl-thiazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (2-acetyl-thiazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; (E) –N– [2– (2-acetyl-thiazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide; [2– (2-Acetyl-oxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; 2-Chloro-benzyl ester of [2– (5-acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -carbamic acid; [2– (4-Acetyl-thiophene-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; (E) –N– [2– (5-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide; [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid; [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2-methyl-oxazole– 4-carboxylic; [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-phenyl-oxazol-4-carboxylic acid; [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethyl-phenyl) –oxazole acid– 4- carboxylic; [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-fluorophenyl) -oxazole-4-carboxylic acid; [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-dimethylamino-phenyl) –oxazole-4-carboxylic acid; [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-chloro-phenyl) -oxazole-4-carboxylic acid; [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole acid– 4- carboxylic; [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (4-fluorophenyl) -oxazole-4-carboxylic acid; [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 5– (3-trifluoromethoxy-phenyl) –oxazole-4-carboxylic acid; [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5– (3-methoxy-phenyl) -oxazole-4-carboxylic acid; (E) –N– [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (4-trifluoromethyl-phenyl) -acrylamide; (E) –N– [2– (4-Acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (3-trifluoromethoxy-phenyl) -acrylamide; [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-methoxy-phenyl) –2-methyl-oxazole– 4- carboxylic; [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2 – methyl-oxazole– 4-carboxylic; [2– (4-Acetyl-thiazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-thiazole-4-carboxylic acid; [2– (4-Acetyl-oxazol-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-phenyl-oxazol-4-carboxylic acid; [2– (5-Acetyl-furan-2-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methoxymethyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 2– (2-methoxy-ethyl) –5-phenyl-oxazole– 4-carboxylic; [2– (5-Acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-butyl-5-phenyl-oxazol-4-carboxylic acid; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-isopropyl-5-phenyl-oxazol-4-carboxylic acid; (E) –N– [2– (4-acetyl-thiazol-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –3– (2-trifluoromethyl-phenyl) -acrylamide; [2– (5-acetyl-furan-2-ylmethyl) –2H– [1,2,3] triazol-4-yl] -amide of 2-benzyl-5-phenyl-oxazol-4-carboxylic acid; 3– {4– [2– (5-Acetyl-furan-2-ylmethyl) -2H– [1,2,3] triazole-4-ylcarbamoyl] -5-phenyl-oxazol-2– tert-butyl ester il} - propionic; [2– (2-acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-fluorophenyl) –2 – methyl-oxazole– 4- carboxylic; [2– (2-Acetyl-oxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 2-methyl-5-m-tolyl-oxazol-4-carboxylic acid; [2– (2-acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (3-chloro-phenyl) –2-methyl-oxazole– 4- carboxylic; [2– (2-Acetyl-oxazol-5-ylmethyl) -2H- [1,2,3] triazol-4-yl] -amide of 5-m-tolyl-oxazol-4-carboxylic acid; [2– (2-acetyl-oxazol-5-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of 2-methyl-5– (3-trifluoromethoxy-phenyl) –oxazole acid– 4- carboxylic; 2-Chloro-benzyl ester of [2– (2-acetyl-oxazol-4-ylmethyl) -2H- [1,2,3] triazole-4-yl] -carbamic acid [2– (5-acetyl-furan – 2-ylmethyl) –2H– [1,2,3] triazol-4-yl] –amide of acid 5– (6-trifluoromethyl-pyridin-2-yl) –oxazole– 4- carboxylic; or a salt of said compound.

14.

As a medicament, a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof.

fifteen.

A pharmaceutical composition containing as active ingredient a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

16.

Use of a compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the prevention or treatment of a disease selected from inflammatory diseases, obstructive airway diseases , allergic conditions, HIV-mediated retroviral infections, cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated diseases and amyloid-mediated disorders; and for the modulation of immune responses.

17.

A compound of formula (I) according to claim 1, or a pharmaceutically acceptable salt thereof, for the prevention or treatment of a disease selected from inflammatory diseases, obstructive diseases of the respiratory tract, allergic disorders, HIV-mediated retroviral infections. , cardiovascular disorders, neuroinflammation, neurological disorders, pain, prion-mediated disorders and amyloid-mediated disorders; and for the modulation of immune responses.