New amide derivatives, pharmaceutical compositions containing them and their uses as SOS1 inhibitors

Abstract

Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, X and Cy1 are as defined in the description. Medicaments.

Description

[0001] FIELD OF THE INVENTION The present invention relates to new amide derivatives, to processes for their preparation, to pharmaceutical compositions containing them and to their uses as Son Of Sevenless homolog 1 (SOS1) inhibitors. The compounds of the present invention inhibit the activity of the SOS1 protein and may be of interest in the treatment of cancer, autoimmune diseases, diseases of immune system and genetic diseases. BACKGROUND OF THE INVENTION RAS proteins play an important role in human cancer (Simanshu et al. Cell 2017, 170, 17-33; Malumbres et al. Nat. Rev. Cancer 2003, 3, 459-465). There are three RAS genes: KRAS, NRAS and HRAS that encode four RAS proteins, with two KRAS isoforms that arise from alternative RNA splicing (KRAS4A and KRAS4B). These proteins play a critical role in transmitting the growth signals from extracellular growth factor binding to intracellular downstream pathways. These growth factors can be, among others, epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and nerve growth factor (NGF) which when bound to their receptors will activate, via Ras activation, the mitogen-activated protein kinase (MAPK) / extracellular regulated kinase (ERK) pathway and phosphoinositide-3-kinase (PI3K) pathways hence regulating cellular division, survival and overall function in normal and altered states such as cancers. RAS proteins functions as guanosine triphosphatases (GTPases) that cycle between an inactive guanosine diphosphate (GDP)-bound state and an active guanosine triphosphate (GTP)-bound state. Mutations in Ras proteins can be found in about 30% of all tumors (Hobbs et al. J. Cell Sci.2016, 129, 1287-1292; Prior et al. Cancer Res.2020, 80, 2969-2974). These missense gain- of-function mutations in RAS genes lead to the hyperactivation of the signaling pathway thus driving tumor initiation and maintenance. These point mutations are typically found within the GTP-binding regions preventing the hydrolysis of bound GTP, leading to RAS constant activation.98% of these mutations are found at one of the three mutational hotspots: G12, G13 and Q61. Over the years, evidence has shown that amino acid substitutions at any one hotspot can have differential biochemical properties leading to differences in oncogenic potencies and functional consequences. Validating this further, it is known that some specific mutations on some isoforms are cancer-type specific. Recent studies have shown that despite being mutated, Ras still require nucleotide cycling for activation based on their intrinsic GTPase activity and sensitivity to extrinsic GTPases. As a consequence, mutant RAS proteins are sensitive to the inhibition of upstream factors such as SOS1 or SHP2. The molecular switch between the active and inactive state is tightly regulated by guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs). GEFs function as activators of Ras by promoting the nucleotide exchange from GDP to GTP, whereas GAPs deactivate Ras-GTP by catalyzing the hydrolysis of the bound GTP to GDP. There are three main types of GEFs: two Son of Sevenless proteins (SOS1 and SOS2), four different isoforms of Ras guanine nucleotide releasing proteins (Ras-GRP1-4) and two Ras guanine nucleotide releasing factors (Ras-GRF1 and2). The most characterized GEFs are SOS proteins, as they play a critical role in cancer (Hillig et al. Adv. Cancer Res.2022, 153, 169-203; Kessler et al. Curr. Opin. Chem. Biol.2021, 62, 109-118). The SOS family is comprised of SOS1 and SOS2, which share about 70% sequence identity (Rojas et al. Genes Cancer 2011, 2, 298-305). SOS1 has been much more studied and is described as the main RAS regulator. SOS are multidomain proteins belonging to the CDC25 homology domain containing GEF family. The N-terminal region contains two tandem histone folds (HFs), a Dbl homology (DH) domain and a pleckstrin homology (PH) domain. The C- terminal region contains the RAS exchanger motif (REM) domain, CDC25 domain, and proline-rich (PR) region (Sondermann et al. Cell 2004, 393-405). Of importance, the N-terminal and C-terminal regions of SOS are joined by a helical linker, which acts as a hinge, allowing SOS to adopt both an active, membrane-bound conformation and an auto-inhibited cytosolic conformation. SOS proteins are recruited to phosphorylated RTKs through an interaction with growth factor receptor 2 (GRB2). Recruitment to the plasma membrane brings SOS and RAS together enabling RAS activation. SOS proteins display a catalytic site and an allosteric site. Through the catalytic site SOS promotes nucleotide exchange, whereas the allosteric site functions as a positive feedback loop, relieving steric occlusion of the catalytic site and is therefore required for full activation of the catalytic site. Out of the two SOS proteins, SOS1 is the most studied and characterized so far. Importantly, SOS1 but not SOS2 is a node in the negative feedback regulation of the KRAS pathway. Relief of SOS1 autoinhibition then sets up a positive feedback loop from mutant RASGTP through SOS1 to wild-type RAS that enhances activation of downstream effectors and is important for proliferation of KRAS mutant pancreatic cancer cells (Sheffels et al. Genes 2021, 12, 662). In addition, SOS1 mutations are found in Noonan syndrome and several types of cancers including lung adenocarcinoma and endometrial cancers (Lepri et al. Hum. Mutat.2011, 32, 760-772; Cai et al. Mol. Cancer Res. 2019, 17, 1002-1012). Targeting Ras for cancer treatment has been long pursued (Moore et al. Nat. Rev. Drug Discov. 2020, 19, 533-552). For a long time, these proteins were considered undruggable. This was in part due to the scarcity of traditional pockets at the surface of the proteins and the high flexibility of the protein. One group of inhibitors that covalently binds to the cysteine of mutant form Kras G12C were recently discovered. These mutant specific inhibitors have the benefit to reach good target inhibition in a defined patient population. It also carries low risk of Kras WT-mediated toxicity. Other Kras mutant specific inhibitors are being pursued in preclinical studies but not all mutations will be addressed. In addition, one important caveat of this approach is the on- target acquired resistance developed in patient (Hofmann et al. Cancer Discov.2022, 12, 924- 937). Therefore, there is still a large unmet need for the treatment of Ras-dependent tumors and, particularly, there remains a need for novel therapeutics to disrupt Ras signaling. To this end, numerous SOS1 inhibitors have been recently developed and published in the literature (He et al., J. Med. Chem.2022, 65, 13158-13171; Hillig et al., PNAS 2019, 116, 2551-2560; Liu et al. ACS Med. Chem. Lett. 2023, 14, 183-190; PCT / EP2018 / 086197) and, particularly, amide derivatives claimed as SOS1 inhibitors have been disclosed in PCT / KR2022 / 012254, PCT / US2021 / 063685 or PCT / US2023 / 012307. But so far, limited success has been achieved clinically. SUMMARY OF THE INVENTION The present invention provides potent selective SOS1 inhibitors of Formula (I) as defined below. We have shown that compounds of Formula (I) have a strong binding affinity on SOS1 and are blocking the interaction between SOS1 and RAS-family members preventing the recycling of KRas into the active GTP-bound form. Therefore, the compounds of the invention could be of interest for a wide range of cancers, particularly Ras family member-associated cancers. In addition, the compounds of the present invention offer potential therapeutic benefit as inhibitors of SOS1-Ras proteins interaction in a cell for treating various forms of cancer, including Ras-associated cancer, SOS1-associated cancer and NF-1 / NF-2 associated cancer. Finally, the compounds of the present invention may provide also therapeutic benefit in genetic and immune diseases. In a first aspect of the invention, the present invention relates to compounds of Formula (I):   wherein: ^ Cy1 represents an aryl group, a heterocycloalkyl group, or a heteroaryl group, ^ R1represents a halogen atom, a linear or branched (C1-C6)alkyl group, or a linear or branched halo(C1-C6)alkyl group, ^ R2represents a linear or branched amino(C1-C6)alkyl group, a linear or branched (C1-C6)alkylamino(C1-C6)alkyl group, a heterocycloalkyl group, a heterocycloalkylalkyl group, or a -CH(CH2-OH)-NH2 group, ^ R3represents a hydrogen atom, a halogen atom, or a linear or branched (C1-C6)alkyl group, ^ R4 represents a hydrogen atom or a halogen atom, ^ R5represents a hydrogen atom, a linear or branched (C1-C6)alkoxy group, or   ^ R6 represents a hydrogen atom, a halogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, a halo(C1-C6)alkoxy group, a linear or branched (C1-C6)alkylsulfonyl group, a linear or branched di(C1-C6)alkylphosphoryl group, a cycloalkyl group, or a heterocycloalkyl group, ^ X represents a -C(R9)- group or a nitrogen atom, ^ R9 represents a hydrogen atom, or the substituents of the pair (R2,R9) form together with the carbon atoms carrying them a non-aromatic 5-membered ring which may contain a nitrogen atom, it being understood that resulting ring may be substituted by from 1 to 2 groups selected from an amino group, a linear or branched (C1-C6)alkylamino group and a linear or branched (C1-C6)alkyl, ^ W represents a bond, an oxygen atom, a -SO2- group, or a linear or branched hydroxy(C1-C6)alkylene group, ^ Cy2represents a cycloalkyl group, a heterocycloalkyl group, or a heteroaryl group, ^ R7 represents a hydrogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched halo(C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, an acetyl group, a propionyl group, an isobutyryl group, a cycloalkyl group, a cycloalkylalkyl group, a heterocycloalkyl group, ^ R8represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. In another aspect of the invention, the present invention relates to compounds of Formula (I):   wherein: ^ Cy1 represents an aryl group or a heteroaryl group, ^ R1represents a halogen atom, a linear or branched (C1-C6)alkyl group, or a linear or branched halo(C1-C6)alkyl group, ^ R2 represents a linear or branched amino(C1-C6)alkyl group, a linear or branched (C1-C6)alkylamino(C1-C6)alkyl group, a heterocycloalkyl group, , ^ R3 represents a hydrogen atom, a halogen atom, or a linear or branched (C1-C6)alkyl group, ^ R4represents a hydrogen atom or a halogen atom, ^ R5 represents a hydrogen atom, a linear or branched (C1-C6)alkoxy group, or   ^ R6 represents a hydrogen atom, a halogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, a linear or branched (C1-C6)alkylsulfonyl group, a linear or branched di(C1-C6)alkylphosphoryl group, a cycloalkyl group, or a heterocycloalkyl group, ^ X represents a -C(R9)- group or a nitrogen atom, ^ R9 represents a hydrogen atom, or the substituents of the pair (R2,R9) form together with the carbon atoms carrying them a non-aromatic 5-membered ring which may contain a nitrogen atom, it being understood that resulting ring may be substituted by from 1 to 2 groups selected from an amino group, a linear or branched (C1-C6)alkylamino group and a linear or branched (C1-C6)alkyl, ^ W represents a bond, an oxygen atom, or a linear or branched hydroxy(C1-C6)alkylene group, ^ Cy2represents a cycloalkyl group, a heterocycloalkyl group, or a heteroaryl group, ^ R7 represents a hydrogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched halo(C1-C6)alkyl group, an acetyl group, a cycloalkyl group, a heterocycloalkyl group, ^ R8 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. In another aspect of the invention, the present invention relates to compounds of Formula (I):   wherein: ^ Cy1 represents an aryl group or a heteroaryl group, ^ R1 represents a halogen atom, a linear or branched (C1-C6)alkyl group, or a linear or branched halo(C1-C6)alkyl group, ^ R2 represents a linear or branched amino(C1-C6)alkyl group, a linear or branched (C1-C6)alkylamino(C1-C6)alkyl group, or a heterocycloalkyl group, ^ R3represents a hydrogen atom, a halogen atom, or a linear or branched (C1-C6)alkyl group, ^ R4represents a hydrogen atom or a halogen atom, ^ R5 represents a hydrogen atom, a linear or branched (C1-C6)alkoxy group, or   ^ R6 represents a hydrogen atom, a halogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, a linear or branched (C1-C6)alkylsulfonyl group, a linear or branched di(C1-C6)alkylphosphoryl group, a cycloalkyl group, or a heterocycloalkyl group, ^ X represents a -C(R9)- group or a nitrogen atom, ^ R9 represents a hydrogen atom, or the substituents of the pair (R2,R9) form together with the carbon atoms carrying them a non-aromatic 5-membered ring which may contain a nitrogen atom, it being understood that resulting ring may be substituted by from 1 to 2 groups selected from an amino group, a linear or branched (C1-C6)alkylamino group and a linear or branched (C1-C6)alkyl, ^ W represents a bond, an oxygen atom, or a linear or branched hydroxy(C1-C6)alkylene group, ^ Cy2represents a cycloalkyl group, a heterocycloalkyl group, or a heteroaryl group, ^ R7 represents a hydrogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched halo(C1-C6)alkyl group, an acetyl group, a cycloalkyl group, a heterocycloalkyl group, ^ R8represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base. In another aspect, the invention provides compounds of Formula (I) as described herein, for use in the treatment of cancer, autoimmune diseases, diseases of immune system and genetic diseases. In a further aspect, the invention provides a pharmaceutical composition comprising the compounds of Formula (I) as described herein, and at least one pharmaceutically acceptable excipient. DEFINITIONS Among the pharmaceutically acceptable acids there may be mentioned, without implying any limitation, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphonic acid, acetic acid, trifluoroacetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulfonic acid, camphoric acid, etc. Among the pharmaceutically acceptable bases there may be mentioned, without implying any limitation, sodium hydroxide, potassium hydroxide, triethylamine, tert-butylamine, etc. “haloalkyl” or “halo(C1-C6)alkyl” means a linear or branched, saturated, monovalent hydrocarbon group having from 1 to 6 carbon atoms, and one or more halogen atoms. More preferably, halogen atoms are selected from fluorine, chlorine and bromine, more preferably fluorine. Among the haloalkyl groups, there may be mentioned, without implying any limitation, -CH2F (or fluoromethyl), -CHF2(or difluoromethyl), -CF3, -CH2-CHF2(or 2,2- difluoroethyl), -CH2-CF3 (or 3,3,3-trifluoroethyl), -(CH2)2-CF3 (or 3,3,3-trifluoropropyl), -CH(CF3)-CH3, etc. “haloalkoxy” or “halo(C1-C6)alkoxy” means a linear or branched, saturated, monovalent (C1-C6)alkoxy group wherein one or more of the hydrogen atoms is replaced with a halogen atom. More preferably, halogen atom is selected from fluorine, chlorine and bromine, more preferably fluorine. Among the haloalkoxy radicals, there may be mentioned, without implying any limitation, -O-CF3, -O-CHF2, -O-CH2-CF3, -O-CF2-CF3, etc. “amino(C1-C6)alkyl” means a linear or branched, monovalent -(C1-C6)alkyl-NH2group. Among the amino(C1-C6)alkyl groups, there may be mentioned, without implying any limitation, -CH2-NH2, -CH2-CH2-NH2, -CH(CH3)-NH2, and the like. “(C1-C6)alkylamino(C1-C6)alkyl” means a monovalent -(C1-C6)alkyl-NH-(C1-C6)alkyl group, wherein each (C1-C6)alkyl is independent. Among the (C1-C6)alkylamino(C1-C6)alkyl groups, there may be mentioned, without implying any limitation, -CH2-CH2-NH-CH3 (also known as dimethylaminoethyl), and the like. “(C1-C6)alkylsulfonyl” means a monovalent -SO2-(C1-C6)alkyl group. Among the (C1-C6)alkylsulfonyl group, there may be mentioned, without implying any limitation, -SO2-CH3, -SO2-CH2-CH3, and the like. “di(C1-C6)alkylphosphoryl” means a monovalent -P(=O)[(C1-C6)alkyl]2group, wherein each (C1-C6)alkyl is independent. Among the di(C1-C6)alkylphosphoryl groups, there may be mentioned, without implying any limitation, -P(=O)(CH3)2, -P(=O)(CH2-CH3)2, -P(=O)(CH3)(CH2-CH3), and the like. “alkylene” or “(C1-C4)alkylene” means a divalent, linear or branched, saturated hydrocarbon radical having from 1 to 4 carbon atoms. Among the alkylene radicals, there may be mentioned, without implying any limitation, -CH2-, -(CH2)2-, -(CH2)3-, -CH(CH3)-, etc. “hydroxy(C1-C6)alkylene” means a divalent, linear or branched, saturated hydrocarbon radical having from 1 to 6 carbon atoms, and one or more hydroxy groups. Among the hydroxyalkylene radicals, there may be mentioned, without implying any limitation, -CH(OH)-, -CH2-CH(OH)-, -CH(OH)-CH2-, and the like. “aryl” means a monocyclic or a fused bicyclic group composed of from 5 to 10 ring members, having at least one aromatic moiety. Among the aryl groups, there may be mentioned, without implying any limitation, phenyl, indanyl, naphthyl, etc. “heteroaryl” means a monocyclic, a fused bicyclic, or a bridged bicyclic group composed of from 5 to 12 ring members, having at least one aromatic moiety and containing from 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen. Among the heteroaryl groups, there may be mentioned, without implying any limitation, furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, thiadiazolyl, isoxazolyl, imidazolyl, pyridazinyl, pyridinyl (or pyridyl), pyridinyl-N-oxide, N-methylpyridiniumyl, pyrimidinyl, pyrazinyl, pyridinonyl, pyrimidinonyl (for example, 6-oxo-1H-pyrimidin-4-yl), triazinyl, indolyl, indazolyl, quinolinyl, isoquinolinyl, thienopyridinyl, imidazopyridinyl, furopyridinyl, oxazolopyridinyl, isoxazolopyridinyl, pyrrolopyridinyl, pyranopyridinyl, thienopyrimidinyl, pyrrolopyridazinyl, quinoxalinyl, quinazolinonyl, benzofuranyl, benzopyranyl, benzodioxolyl, benzimidazolyl, benzothienyl, benzotriazolyl, benzothiazolyl, benzoxadiazolyl, dihydrobenzofuranyl, dihydroindolyl, dihydroquinolinyl, dihydroisoindolyl, dihydropyrrolizinyl, dihydrocyclopentathienyl, dihydroquinoxalinyl, dihydrobenzodioxinyl, dihydrothienodioxinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrahydroindolizinyl, tetrahydroquinazolinyl, tetrahydroindazolyl, tetrahydronaphthyridinyl, tetrahydro-5,8- ethanoquinolinyl, tetrahydrobenzothienyl, cyclopentapyridinyl, cyclopentapyrimidinyl, hexahydropentalenopyridinyl, cycloheptapyridinyl, dioxino[2,3-b]pyridinyl, etc. “cycloalkyl” means a monocyclic, a fused bicyclic, a spiro bicyclic, or a bridged bicyclic non- aromatic carbocyclic group composed of from 3 to 10 ring members. Among the cycloalkyl groups, there may be mentioned, without implying any limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantyl, bicyclo[1.1.1]pentanyl, spiro[3.3]heptanyl, etc. “heterocycloalkyl” means a monocyclic, a fused bicyclic, or a spiro bicyclic non-aromatic group composed of from 3 to 10 ring members, containing from 1 to 3 heteroatoms selected from oxygen, sulfur, nitrogen and silicium, and may have one double bond. In a particular embodiment, heterocycloalkyl can be deuterated. Among the heterocycloalkyl groups, there may be mentioned, without implying any limitation, azetidinyl, azepanyl, dihydropyrrolyl, tetrahydropyranyl, dihydropyranyl, tetrahydropyridinyl (or dihydro-2H-pyridinyl), piperidinyl (or piperidyl), piperazinyl, morpholinyl, pyrrolidinyl, dioxanyl, dihydrofuranyl, tetrahydrofuranyl, thianyl, dioxothianyl, oxetanyl, dioxothiazinyl (or diketothiazinanyl), thiazinanyl, tetrahydrotriazinyl (or dihydro-4H-triazinyl), 5,6-dihydro-1,2,4-triazinyl, tetrahydropyrimidinyl, 6,7-dihydro-4H-pyrazolo[1,5-a]pyrazinyl, diazaspiro[3.5]nonanyl (particularly, 2,7-diazaspiro[3.5]nonan-2-yl or 2,8-diazaspiro[3.5]nonan-2-yl), azasilinanyl, oxazaspiro[4.4]nonanyl (particularly, 2-oxa-7-azaspiro[4.4]nonan-7-yl), azaspiro[3.3]heptanyl, diazaspiro[3.3]heptanyl (particularly, 1,6-diazaspiro[3.3]heptan-1-yl or 2,6-diazaspiro[3.3]heptan-6-yl), oxazaspiro[3.3]heptanyl (particularly, 6-oxa-1- azaspiro[3.3]heptan-1-yl or 2-oxa-6-azazspiro[3.3]heptan-6-yl), oxazaspiro[2.5]octanyl (particularly, 4-oxa-7-azaspiro[2.5]octan-7-yl), oxazaspiro[3.4]octanyl (particularly, 2-oxa-7- azaspiro[3.4]octan-7-yl or 6-oxa-2-azaspiro[3.4]octan-2-yl), oxazaspiro[3.5]nonanyl, oxazaspiro[5.5]undecanyl, oxazaspiro[4.5]decanyl (particularly, 8-oxa-2-azaspiro[4.5]decan- 2-yl), oxaphosphinanonyl, etc. Among the heterocycloalkyl groups which can be deuterated, there may be mentioned, without implying any limitation, 2,2,3,3,5,5,6,6- octadeuteriopiperazin-1-yl, 2,2,6,6-tetradeuterio-3H-pyran-4-yl, etc. The term “cycloalkylalkyl” used herein refers to a linear or branched -(C1-C4)alkylene-Z group, wherein “Z” is a cycloalkyl group. Among the cycloalkylalkyl groups, there may be mentioned, without implying any limitation, -CH2-cyclopropyl, -(CH2)2-cyclopropyl, -CH2-cyclobutyl, etc. The term “heterocycloalkylalkyl” used herein refers to a linear or branched -(C1-C4)alkylene-Z group, wherein “Z” is a heterocycloalkyl group. In a particular embodiment, “Z” is a heterocycloalkyl group substituted by one or two halogen atoms, preferably by one or two fluorine atoms. Among the heterocycloalkylalkyl groups, there may be mentioned, without implying any limitation, -CH2-morpholinyl, -(CH2)2-morpholinyl, -CH2-pyrrolidinyl, “acetyl” means a -C(=O)-CH3 group. “amino” means a -NH2group. Among the pharmaceutical compositions according to the invention there may be mentioned more especially those that are suitable for oral, parenteral, nasal, per- or trans-cutaneous, rectal, perlingual, ocular or respiratory administration, especially tablets or dragées, sublingual tablets, sachets, paquets, capsules, glossettes, lozenges, suppositories, creams, ointments, dermal gels, and drinkable or injectable ampoules. The pharmaceutical compositions according to the invention comprise one or more excipients or carriers selected from diluents (such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycerol…), lubricants (such as silica, talc, stearic acid and its magnesium and calcium salts, polyethylene glycol…), binders (such as magnesium aluminum silicate, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidone…), disintegration agents (such as agar, alginic acid and its sodium salt, effervescent mixtures…), stabilizers, preservatives, absorbents, colorants, sweeteners, flavorings, etc. The administration route is preferably the oral route or the intravenous route, and the corresponding pharmaceutical compositions may allow the instantaneous or delayed release of the active ingredients. Among the combinations of a compound of Formula (I) with an anticancer agent according to the invention, there may be mentioned more especially those that are suitable for a simultaneous administration or a sequential administration. The combinations according to the invention comprise a compound of Formula (I) combined to anti-cancer agents selected from genotoxic agents, mitotic poisons, anti-metabolites, proteasome inhibitors, enzymes inhibitors, signaling proteins inhibitors, transcription factor inhibitors, epigenetic factor inhibitors, kinase inhibitors, protein-protein interaction inhibitors, immunomodulators, E3 ligase inhibitors, chimeric antigen receptor T-cell therapy and antibodies. The compounds of the combination may moreover be administered in the form of two separate pharmaceutical compositions, each containing one of the active ingredients, or in the form of a single pharmaceutical composition, in which the active ingredients are in admixture. As used herein, the term “treat”, “treating” or “treatment” of any disease or disorder refers in one embodiment, to ameliorating the disease or disorder (i.e., slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof). In another embodiment “treat”, “treating” or “treatment” refers to alleviating or ameliorating at least one physical parameter including those which may not be discernible by the patient. In yet another embodiment, “treat”, “treating” or “treatment” refers to modulating the disease or disorder, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both. The term “Ras-associated cancer” as used herein refers to cancers associated with or having a dysregulation of a Ras gene, a Ras protein, or the expression or activity or level of any (e.g., one or more) of the same (e.g., any of the types of dysregulation of a Ras gene, a Ras protein, or the expression or activity or level of any of the same, as described herein). Non-limiting examples of a Ras-associated cancer are described herein. In some embodiments, a Ras- associated cancer can be a KRas-associated cancer, a HRas-associated cancer, a NRas- associated cancer, or a combination thereof. The term “SOS1-associated cancer” as used herein refers to cancers associated with or having a dysregulation of a SOS1 gene, a SOS1-GEF (also called herein SOS1 protein), or the expression or activity or level of any (e.g., one or more) of the same (e.g., any of the types of dysregulation of a SOS1 gene, a SOS1 protein, or the expression or activity or level of any of the same, as described herein). Non-limiting examples of a SOS1-associated cancer are described herein. As used herein, a “NF-1 / NF-2-associated cancer” refers to cancer associated with or mediated by or having a loss-of-function mutation in the neurofibromin (NF-1) gene or neurofibromin 2 (NF-2) gene. Non-limiting examples of a NF-1 / NF-2-associated cancer are described herein. Among the treatment or the prevention of cancers envisaged, there may be mentioned, without implying any limitation, of Ras-associated cancer, SOS1-associated cancer and NF-1 / NF-2 associated cancer. These cancers may be, without implying any limitation hematological malignancies and solid tumors, more particularly, pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular cancer, breast cancer, ovarian cancer, prostate cancer, glioblastoma, renal cancer, sarcomas, glioma and malignant peripheral nerve sheath tumors. In another aspect, the disease to be treated or prevented with compound of Formula (I) is a RASopathy. The term “RASopathy” means a group of rare genetic diseases caused by mutations in certain genes that make proteins involved in the Ras / MAPK cell signaling pathway. Preferably, RASopathy is selected from the group consisting of neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lengitines, capillary malformation- arteriovenous malformation syndrome, Costello syndrome, cardiofaciocutaneous syndrome, Legius syndrome and hereditary gingival fibromatosis. Actual dosage levels of the active ingredients in the pharmaceutical compositions of this invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The selected dosage level will depend upon a variety of factors including the activity of the particular compound of the present invention employed, the route of administration, the time of administration, the rate of excretion or metabolism of the particular compound being employed, the rate and extent of absorption, the duration of the treatment, other drugs, compounds and / or materials used in combination with the particular compound employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A suitable daily dose of a compound of the invention will depend upon the factors described above and may range from 0.01 mg to 2.5 g per day in one or more administration(s). DETAILED DESCRIPTION Described below are a number of preferred and advantageous embodiments of the invention. It will be recognized that features specified in each preferred embodiment may be combined with other specified features to provide further preferred embodiments of the present invention. Preferably, Cy1represents a phenyl group, a thienyl group, a pyridinyl group, a pyridinyl-N- oxide group, a N-methylpyridiniumyl group, a pyrimidinyl group, a pyrimidinonyl group, a pyrazinyl group, a thiazolyl group, an oxazolyl group, an isoxazolyl group, a 1,3,4-oxadiazolyl group, a 1,2,4-oxadiazolyl group, a 1,3,4-thiadiazolyl group, a 1,4,5,6-tetrahydropyrimidinyl group, a pyridazinyl group, an indolinyl group, a triazinyl group, or a dihydro-1,4-benzoxazinyl group. In another preferred embodiment, Cy1 represents a phenyl group, a thienyl group, a pyridinyl group, a pyridinyl-N-oxide group, a N-methylpyridiniumyl group, a pyrimidinyl group, a pyrazinyl group, a thiazolyl group, an oxazolyl group, an isoxazolyl group, a 1,3,4- oxadiazolyl group, a 1,2,4-oxadiazolyl group, a 1,3,4-thiadiazolyl group, a 1,4,5,6- tetrahydropyrimidinyl group, a pyridazinyl group, an indolinyl group, a triazinyl group, or a dihydro-1,4-benzoxazinyl group. In another preferred embodiment, Cy1represents a phenyl group, a thienyl group, an oxazolyl group, a 1,3,4-oxadiazolyl group, a pyridinyl group, a pyridinyl-N-oxide group, a N-methylpyridiniumyl group, a pyrimidinyl group, a pyrazinyl group, a thiazolyl group, a pyridazinyl group, an indolinyl group, a triazinyl group, or a dihydro- 1,4-benzoxazinyl group. Advantageously, Cy1 represents a phenyl group, a thienyl group, an oxazolyl group, a 1,3,4-oxadiazolyl group, a pyridinyl group, a pyridinyl-N-oxide group, a pyrimidinyl group, a pyrazinyl group, a thiazolyl group, an indolinyl group, or a dihydro-1,4- benzoxazinyl group. More preferably, Cy1 represents a phenyl group, a thienyl group, an oxazolyl group, a 1,3,4-oxadiazolyl group, a pyridinyl group, a pyrimidinyl group, or a pyrazinyl group. Even more preferably, Cy1represents a pyridinyl group, an oxazolyl group, a 1,3,4-oxadiazolyl group, a pyrazinyl group, or a pyrimidinyl group. Even more preferably, Cy1 represents a pyridinyl group or a pyrimidinyl group. In a preferred embodiment, when Cy1represents a pyridinyl ring, it represents wherein R5 and R6 are as defined for Formula (I). In a preferred embodiment, when Cy1 represents a pyridinyl ring, it representsa wherein R5and R6are as defined for Formula (I). In a preferred embodiment, R1represents a chlorine atom, a fluorine atom, a methyl group, a -CF3group, or a -CHF2group. In another preferred embodiment, R1represents a chlorine atom, a methyl group, a -CF3 group, or a -CHF2 group. More preferably, R1 represents a chlorine atom or a -CF3 group. Even more preferably, R1 represents a -CF3 group. Preferably, R2 represents a -CH2-NH2 group, a -CH2-NH-CH3 group, a -CH(CH3)-NH2 group, a -CH(CH2-OH)-NH2 group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azaspiro[3.3]heptanyl group,aa In another preferred embodiment, R2represents a -CH2-NH2group, a -CH2-NH-CH3group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azaspiro[3.3]heptanyl group,aa Advantageously, R2 represents a -CH2-NH2 group, a -CH2-NH-CH3 group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, or an azaspiro[3.3]heptanyl group.More advantageously, R2represents a -CH2-NH2group, agroup, a pyrrolidinyl group, or a group. In one preferred embodiment, R2 represents a pyrrolidinyl group or a -CH2-NH2 group. Even more advantageously, R2represents a -CH2-NH2group. Preferably, R3 represents a hydrogen atom, a chlorine atom, a fluorine atom, or a methyl group. More preferably, R3 represents a hydrogen atom. Preferably, R4 represents a hydrogen atom, a fluorine atom, or a chlorine atom. More preferably, R4 represents a hydrogen atom or a chlorine atom. Even more preferably, R4 represents a hydrogen atom. Preferably, R5 represents a hydrogen atom, a methoxy group, or  a wherein W, Cy2, R7and R8are as defined for Formula (I).   wherein W, Cy2, R7and R8are as defined for Formula (I). Advantageously, R6 represents a hydrogen atom, a chlorine atom, a methyl group, a methoxy group, a -O-CHF2group, a -SO2-CH2-CH3group, a -P(=O)-(CH2-CH3)2group, a cyclopropyl group, or an oxetanyl group. In another preferred embodiment, R6represents a hydrogen atom, a chlorine atom, a methyl group, a methoxy group, a -SO2-CH2-CH3 group, a -P(=O)-(CH2- CH3)2 group, a cyclopropyl group, or an oxetanyl group. Preferably, R6 represents a hydrogen atom, a methyl group, a methoxy group, a -P(=O)-(CH2-CH3)2group, or a cyclopropyl group. More advantageously, R6 represents a hydrogen atom, a methoxy group, or a cyclopropyl group. Even more advantageously, R6 represents a hydrogen atom. Preferably, X represents a -C-R9- group. Preferably, W represents a bond, an oxygen atom, a -SO2- group, or a -CH(OH)- group. In another preferred embodiment, W represents a bond, an oxygen atom, or a -CH(OH)- group. More preferably, W represents a bond or an oxygen atom. Even more preferably, W represents a bond. In a preferred embodiment, Cy2 represents a heterocycloalkyl group or a heteroaryl group. In one another preferred embodiment, Cy2 represents a cyclopropyl group, a tetrahydrofuranyl group, a pyrrolidinyl group, a morpholinyl group, a piperidinyl group, a piperazinyl group, a tetrahydropyranyl group, a dihydropyranyl group, a tetrahydropyridinyl group, a thiazolyl group, a 1,3,4-thiadiazolyl group, an oxazaspiro[3.3]heptanyl group, an oxazaspiro[2.5]octanyl group, an azabicyclo[3.1.0]hexanyl group, an oxaspiro[2.5]octanyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazaspiro[4.5]decanyl group, a 6,7-dihydro-4H- pyrazolo[1,5-a]pyrazinyl group, a diazaspiro[3.5]nonanyl group, an azasilinanyl group, an oxazaspiro[4.4]nonanyl group, a 5,6-dihydro-1,2,4-triazinyl group, a pyridonyl group, a dihydropyrrolyl group, a pyrrolyl group, a pyrimidinyl group, an oxazaspiro[3.4]octanyl group, an oxaphosphinanonyl group, a pyridinyl group, a pyridinyl-N-oxide group, a tetrahydrotriazinyl group, a 2,2,3,3,5,5,6,6-octadeuteriopiperazin-1-yl group, a 2,2,6,6- tetradeuterio-3H-pyran-4-yl group, or a diazaspiro[3.3]heptanyl group. In another preferred embodiment, Cy2represents a cyclopropyl group, a tetrahydrofuranyl group, a pyrrolidinyl group, a morpholinyl group, a piperidinyl group, a piperazinyl group, a tetrahydropyranyl group, a dihydropyranyl group, a tetrahydropyridinyl group, a thiazolyl group, a triazolyl group, an oxazaspiro[3.3]heptanyl group, an oxazaspiro[2.5]octanyl group, an azabicyclo[3.1.0]hexanyl group, an oxaspiro[2.5]octanyl group, a pyrazolyl group, an imidazolyl group, a pyridonyl group, a dihydropyrrolyl group, a pyrrolyl group, a pyrimidinyl group, an oxazaspiro[3.4]octanyl group, an oxaphosphinanonyl group, a pyridinyl group, a pyridinyl-N-oxide group, a tetrahydrotriazinyl group, or a diazaspiro[3.3]heptanyl group. Preferably, Cy2 represents a tetrahydrofuranyl group, a pyrrolidinyl group, a morpholinyl group, a piperidinyl group, a piperazinyl group, a tetrahydropyranyl group, a thiazolyl group, a dihydropyranyl group, a tetrahydropyridinyl group, a triazolyl group, an oxazaspiro[3.3]heptanyl group, an oxazaspiro[2.5]octanyl group, a pyrazolyl group, a pyridonyl group, a dihydropyrrolyl group, a pyrrolyl group, a pyrimidinyl group, an oxazaspiro[3.4]octanyl group, a pyridinyl group, or a tetrahydrotriazinyl group. Advantageously, Cy2 represents a tetrahydrofuranyl group, a morpholinyl group, a piperidinyl group, a piperazinyl group, a tetrahydropyranyl group, a thiazolyl group, a dihydropyranyl group, a tetrahydropyridinyl group, a triazolyl group, an oxazaspiro[3.3]heptanyl group, a pyrazolyl group, a pyridonyl group, a dihydropyrrolyl group, a pyrrolyl group, an oxazaspiro[3.4]octanyl group, a pyridinyl group, or a tetrahydrotriazinyl group. More advantageously, Cy2represents a piperazinyl group, a dihydropyranyl group, a tetrahydropyranyl group, a tetrahydrofuranyl group, a triazolyl group, an oxazaspiro[3.4]octanyl group or a morpholinyl group. Even more advantageously, Cy2 represents a piperazinyl group, a tetrahydropyranyl group, a dihydropyranyl group, or a morpholinyl group. Even more advantageously, Cy2represents a piperazinyl group, a dihydropyranyl group, or a morpholinyl group. In one preferred embodiment, Cy2 represents a piperazinyl group. Advantageously, R7 represents a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a methoxy group, an ethoxy group, an isopropyl group, a -CH2F group, a -CHF2group, a -CF3group, an acetyl group, a propionyl group, an isobutyryl group, a cyclopropyl group, a -CH2-cyclopropyl group, an oxetanyl group, a morpholinyl group, a tetrahydropyranyl group, In another preferred embodiment, R7 represents a hydrogen atom, a methyl group, an isopropyl group, a -CH2F group, a -CHF2group, a -CF3group, an acetyl group, a cyclopropyl group, an oxetanyl group, a morpholinyl group, a tetrahydropyranyl group, More advantageously, R7represents a hydrogen atom, a methyl group, an isopropyl group, an acetyl group, a cyclopropyl group, an oxetanyl group, Even more advantageously, R7represents a hydrogen atom, a group, group.  Even more advantageously, R7 represents a hydrogen atom or agroup. In one another preferred embodiment, R7represents a group. Preferably, R8 represents a hydrogen atom or a methyl group. More preferably, R8 represents a hydrogen atom. Preferably, R9 represents a hydrogen atom. In one preferred embodiment, when the substituents of the pair (R2,R9) form together with the carbon atoms carrying them a non-aromatic 5-membered ring,   , wherein R10 represents an amino group or a linear or branched (C1-C6)alkylamino group, R11 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, and R12 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group. Preferably, R10 represents an amino group or a -NH-CH3 group. Preferably, R11represents a hydrogen atom or a methyl group. Preferably, R12 represents a hydrogen atom or a methyl group. An advantageous possibility consists of compounds of Formula (I-a):   wherein R1, R2, R3, R4, R5, R6, Cy1and X are as defined for Formula (I). An advantageous possibility consists of compounds of Formula (I-b):   wherein R1, R2, R3, R4, R5, R6, Cy1and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-c):   wherein R1, R2, R3, R4, R5, R6, Cy1 and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-d):   wherein R1, R2, R3, R4, R6, R7, R8, Cy1, Cy2, W and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-e):   wherein R1, R2, R3, R4, R6, R7, R8, Cy1, Cy2, W and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-f):   wherein R1, R2, R3, R4, R6, R7, R8, Cy1, Cy2 and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-g):   wherein R1, R2, R3, R4, R6, R7, R8, Cy1, Cy2and X are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-h): wherein R4, R5, R6 and Cy1 are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-i): wherein R4, R5, R6 and Cy1 are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-j): wherein R4, R6, R7, R8, Cy1, Cy2and W are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-k): wherein R4, R6, R7, R8, Cy1, Cy2 and W are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-l): wherein R4, R6, R7, R8, Cy1and Cy2are as defined for Formula (I). Another advantageous possibility consists of compounds of Formula (I-m): wherein R4, R6, R7, R8, Cy1 and Cy2 are as defined for Formula (I). In Formulae (I-a), (I-c), (I-e), (I-g), (I-i), (I-k) and (I-m), the asymmetric carbon has an (R)- configuration. Preferred compounds according to the invention are: - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5-(3,6- dihydro-2H-pyran-4-yl)nicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-isonicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5-[(3S)- tetrahydrofuran-3-yl]oxy-nicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-[(3R)- tetrahydrofuran-3-yl]oxy-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[4- (cyclopropanecarbonyl)piperazino]picolinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- tetrahydropyran-4-yl-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- tetrahydropyran-4-yl-pyrazinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- morpholino-picolinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- morpholino-pyrazine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[(3R)- tetrahydrofuran-3-yl]oxy-pyrimidine-2-carboxamide; - 4-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyridine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yloxy-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-[4-(oxetan- 3-ylmethyl)piperazin-1-yl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-(2-oxa-7- azaspiro[3.4]octan-7-yl)pyridine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6-[4- (cyclopropanecarbonyl)piperazin-1-yl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(2-oxa-7- azaspiro[3.4]octan-7-yl)pyrimidine-4-carboxamide; - 2-(oxan-4-yl)-N-[(1R)-1-[4-[2-pyrrolidin-2-yl-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyrimidine-4-carboxamide; - 2-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- tetrahydropyran-4-yl-1,3,4-oxadiazole-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6-(3- methyltriazol-4-yl)pyrazine-2-carboxamide; or - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-oxazole-5-carboxamide. In one another embodiment, preferred compounds according to the invention are: - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5-(3,6- dihydro-2H-pyran-4-yl)nicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-isonicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[4- (cyclopropanecarbonyl)piperazino]picolinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- tetrahydropyran-4-yl-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- tetrahydropyran-4-yl-pyrazinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- morpholino-picolinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- morpholino-pyrazine-2-carboxamide; - 4-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyridine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-[4-(oxetan- 3-ylmethyl)piperazin-1-yl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-(2-oxa-7- azaspiro[3.4]octan-7-yl)pyridine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6-[4- (cyclopropanecarbonyl)piperazin-1-yl]pyrimidine-4-carboxamide; or - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(2-oxa-7- azaspiro[3.4]octan-7-yl)pyrimidine-4-carboxamide; - 2-(oxan-4-yl)-N-[(1R)-1-[4-[2-pyrrolidin-2-yl-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyrimidine-4-carboxamide; - 2-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- tetrahydropyran-4-yl-1,3,4-oxadiazole-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6-(3- methyltriazol-4-yl)pyrazine-2-carboxamide; or - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-oxazole-5-carboxamide. In one another embodiment, preferred compounds according to the invention are: - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[4- (cyclopropanecarbonyl)piperazino]picolinamide; or - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-oxazole-5-carboxamide. In one another embodiment, preferred compounds according to the invention are: - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide; or - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[4- (cyclopropanecarbonyl)piperazino]picolinamide. Another aspect of the invention concerns a compound of Formula (V): wherein R1, R2, R3, R4 and X are as defined in Formula (I). Advantageously, compound of Formula (V) can be used as synthesis intermediate for the preparation of compounds of Formula (I). In some embodiment, for the need of the preparation of compound of Formula (I) and as exemplified in Examples section, compound of Formula (V) can be protected by amino-protecting groups such as Boc, Fmoc, etc. Preferably, compound of Formula (V) is 1-[4-[5-(aminomethyl)-2- (trifluoromethyl)phenyl]phenyl]ethanamine. Pharmacological studies of the compounds of the invention have shown that they have strong binding affinity on SOS1 and are blocking the interaction between SOS1 and RAS-family members preventing the recycling of KRas into the active GTP-bound form. Therefore, the compounds of the invention could be of interest for a wide range of cancers, particularly Ras family member-associated cancers. In addition, the compounds of the present invention offer potential therapeutic benefit as inhibitors of SOS1-Ras proteins interaction in a cell for treating various forms of cancer, including Ras-associated cancer, SOS1-associated cancer and NF- 1 / NF-2 associated cancer. Finally, the compounds of the present invention may provide also therapeutic benefit in genetic and immune diseases. The present invention relates also to pharmaceutical compositions comprising at least one compound of Formula (I) or an addition salt thereof with a pharmaceutically acceptable acid or base in combination with one or more pharmaceutically acceptable excipients. In particular, these pharmaceutical compositions are interesting for use as SOS1 inhibitors, particularly, in the treatment of cancer (haematological malignancy and solid tumor), autoimmune diseases, diseases of immune system and genetic diseases. Preferably, said pharmaceutical compositions are interesting for use as SOS1 inhibitors in the treatment or the prevention of Ras-associated cancer, SOS1-associated cancer and NF-1 / NF-2 associated cancer. Particularly, these pharmaceutical compositions can be used in the treatment of cancer selected from pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular cancer, breast cancer, ovarian cancer, prostate cancer, glioblastoma, renal cancer, sarcomas, glioma and malignant peripheral nerve sheath tumors. In one another embodiment, these pharmaceutical compositions can be used in the treatment of genetic diseases, particularly in the treatment of neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lengitines, capillary malformation-arteriovenous malformation syndrome, Costello syndrome, cardiofaciocutaneous syndrome, Legius syndrome and hereditary gingival fibromatosis. Furthermore, the present invention relates also to the combination of a compound of Formula (I) with small molecules including but not limited to anticancer agents selected from genotoxic agents, mitotic poisons, anti-metabolites, proteasome inhibitors, enzymes inhibitors, signaling proteins inhibitors, transcription factor inhibitors, epigenetic factor inhibitors, kinase inhibitors, protein-protein interaction inhibitors, immunomodulators, E3 ligase inhibitors, as well as chimeric antigen receptor T-cell therapy and antibodies. In one embodiment, the present invention relates also to pharmaceutical compositions comprising that type of combination and their use in the manufacture of medicaments for use in the treatment of cancer, especially pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular cancer, breast cancer, ovarian cancer, prostate cancer, glioblastoma, renal cancer, sarcomas, glioma and malignant peripheral nerve sheath tumors. EXAMPLES The compounds of the present disclosure can be prepared in a number of ways well known to those skilled in the art of organic synthesis. By way of example, compounds of the invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. It is understood that at any moment considered appropriate during the processes described below, some groups (halogen, hydroxy, amino…) of the starting reagents or of the synthesis intermediates can be protected, subsequently deprotected and functionalized, as required by the synthesis. Preferred methods include but are not limited to those methods described below. In a particular embodiment, compounds of Formula (I) can be synthesized by following the steps outlined in General Schemes 1 and 2 which comprise different sequences of preparing intermediates II, IV and V. Starting materials I, III and VI are either commercially available or made by known procedures in the reported literature or as illustrated. General Scheme 1 wherein R1, R2, R3, R4 and X are as defined in Formula (I) and R’ represents a hydrogen atom, a linear or branched (C1-C6) alkyl group, or the pair (R’,R’) form with the oxygen carrying them an optionally methylated ring. The general way of preparing intermediate IV containing biphenyl moiety by using intermediate II is outlined in General Scheme 1. Starting material I was transformed after amine protection to yield the corresponding boronic ester derivative II which underwent a Suzuki reaction with brominated reactant III using a palladium catalyst at high temperatures to provide intermediate IV. General Scheme 2 wherein R1, R2, R3, R4, R5, R6, Cy1and X are as defined in Formula (I). The general way of preparing compounds of Formula (I) is outlined in General Scheme 2. The preparation of intermediate V was obtained through an amine deprotection. Peptidic coupling reaction was performed using carboxylic acid VI (or its corresponding sodium / lithium carboxylate) to yield compounds of Formula (I). A mixture of enantiomers, diastereoisomers resulting from the processes described above can be separated into their single components by chiral salt technique, chromatography using normal phase, reverse phase or chiral column, depending on the nature of the separation. GENERAL SYNTHETIC REMARKS All reagents obtained from commercial sources were used without further purification. Anhydrous solvents were obtained from commercial sources and used without further drying. The reactions were monitored using LCMS instruments and / or TLC. Thin layer chromatography was conducted with 5 cm × 10 cm plates coated with Merck Type 60 F254silica-gel.1H-NMR measurements were performed on Bruker Avance III HD 400 MHz spectrometer, using DMSO-d6or CDCl3as solvent (purchased from Eurisotop).1H NMR data is in the form of delta values, given in part per million (ppm), using the residual peak of the solvent (2.50 ppm for DMSO-d6and 7.26 ppm for CDCl3) as internal standard. Splitting patterns are designated as: s (singlet), d (doublet), t (triplet), q (quartet), quin (quintet), spt (septuplet), m (multiplet), br s (broad singlet), br d (broad doublet), br t (broad triplet), br m (broad multiplet), dd (doublet of doublets), br dd (broad doublet of doublets), td (triplet of doublets), dt (doublet of triplets), qd (quartet of doublets), tt (triplet of triplets), ddd (doublet of doublets of doublets), ddt (doublet of doublets of triplets). HRMS measurements were performed on a LTQ OrbiTrap Velos Pro mass spectrometer. The system was powered by Orbitrap Technology from ThermoFisher Scientific GmbH, (Bremen, Germany) coupled to an ultra-high-pressure liquid chromatography (UHPLC) system (VANQUISH, ThermoFisher Scientific, Bremen, Germany) using a BEH C18 column (2.1 mm × 100 mm- 1.7 µm). Full-scan acquisition was performed over the range m / z 115–1500 at a resolving power of 30,000 (FWHM). A HESI (heated electrospray) ion source was operated in the positive mode. The parameters were as follows: electrospray voltage, 3.5 kV; heater temperature, 300 °C; capillary temperature, 300 °C; S-lens RF level, 55%. Nitrogen (N2) was used as the sheath and auxiliary gas, and helium (He) was used as the collision gas. ESI were determined on a Waters SQD UPLC. Chemical names were generated using Biovia Draw Version 18.1 or using Biovia PipelinePilot Version 2023 by Dassault Systemes. GENERAL PROCEDURES General Procedure 1: Phthalimide cleavage To a stirred solution of the phthalimide-N-protected amine (1.0 eq.) in ethanol (0.1 M) was added hydrazine (5.0 eq.) at room temperature and the mixture was stirred until full conversion of the starting material. The mixture was concentrated under reduced pressure and the residues were purified by silica gel column chromatography or reverse phase chromatography to afford the corresponding amine. General Procedure 2: Suzuki coupling General Procedure 2A: Halogenated aryl (1.0 eq.) was dissolved into a 1:4 water / 1,4-dioxane mixture (0.15 M) which was degassed for 10 minutes with argon. Then, boronic ester (1.5 eq.), potassium fluoride (3.0 eq.) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1:1) (6 mol%) were added. The system was purged with argon and heated to 100 °C. After completion of the reaction, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography to afford the expected product. General Procedure 2B: Halogenated aryl (1.0 eq.) was dissolved into a 4:1 toluene / ethanol mixture (0.15 M) which was degassed for 10 minutes with argon. Then, boronic ester (1.2 eq.), sodium carbonate (3.0 eq.) and palladium triphenylphosphine (2 mol%) were added. The system was purged with argon and heated to 60 °C. After completion of the reaction, the mixture was concentrated under reduced pressure and the residues were purified by silica gel column chromatography to afford the expected product. General Procedure 2C: Halogenated aryl (1.0 eq.) was dissolved into a 3:1 toluene / water mixture (0.1 M) which was degassed for 10 minutes with argon. Then, boronic acid (2.1 eq.), potassium phosphate (3.0 eq.), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl and palladium acetate (II) (5 mol%) were added. The system was purged with argon and heated to 90 °C. After completion of the reaction, the mixture was concentrated under reduced pressure and the residues were dissolved into dichloromethane and 1 N aqueous citric acid. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the crude expected product. General Procedure 3: Boc cleavage General Procedure 3A: To the tert-butyl-N-carbamate (1.0 eq.) in neat conditions was added trifluoroacetic acid at room temperature. After complete conversion of the starting material, the mixture was concentrated under reduced pressure and the residues were purified by reverse phase chromatography or by silica gel column chromatography or eluted through a PoraPak Rxn CX (polymer-based chromatography product using a strong cation-exchange sorbent) to give the expected amine. General Procedure 3B: To the tert-butyl-N-carbamate (1.0 eq.) in 1,4-dioxane was added 4 N hydrogen chloride in 1,4-dioxane at room temperature. After complete conversion of the starting material, the mixture was concentrated under reduced pressure and the residues were purified or used directly in the next step. General Procedure 3C: To a stirred solution of tert-butyl-N-carbamate (1.0 eq.) in dichloromethane was added trifluoroacetic at room temperature. After completion of the reaction, the mixture was concentrated under reduced pressure and the residues were purified by reverse phase chromatography or by silica gel column chromatography or eluted through a PoraPak Rxn CX (polymer-based chromatography product using a strong cation-exchange sorbent) to give the expected amine. General Procedure 4: Ester saponification General Procedure 4A: The ester (1.0 eq.) was dissolved in methanol (0.1 M) and an aqueous 1 N sodium hydroxide solution (5.0 eq.) was added at room temperature. After completion of the reaction, the mixture was concentrated under reduced pressure and aqueous 1 N hydrogen chloride (5.0 eq.) was added and the crude mixture was freeze-dried to afford the corresponding carboxylic acid, which was used into the next step without further purification. General Procedure 4B: The ester (1.0 eq.) was dissolved into a 2:1 tetrahydrofuran / water mixture and lithium hydroxide (3.0 eq.) was added at room temperature. After completion of the reaction, water was added and the crude mixture was freeze-dried to afford the corresponding lithium carboxylate used into the next step without further purification. General Procedure 5: Buchwald coupling A stirred mixture of arylbromide (1.0 eq.) and amine (1.2 eq.) in anhydrous 1,4-dioxane (0.2 M) was degassed under argon for 10 min. Then, palladium acetate (II) (2 mol%), cesium carbonate (3.0 eq.) and BINAP ((±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene; 10 mol%) were added and the mixture was heated to 100 °C until completion of the reaction. The solvent was removed under reduced pressure and the residues were purified by silica gel column chromatography to afford the expected product. General Procedure 6: General Procedure 6A: To a stirred solution of carboxylic acid (1.0 eq.) in N, N-dimethylformamide (0.1 M) were added N, N-diisopropylethylamine (2.0 eq.), N, N, N′, N′-tetramethyl-O-(1H-benzotriazol-1- yl)uronium hexafluorophosphate (1.3 eq.) and the amine (1 eq.) then the mixture was stirred at room temperature until completion of the reaction. The mixture was dissolved with water and dichloromethane and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography or reverse phase column chromatography to afford the expected amide. General Procedure 6B: To a stirred solution of carboxylic acid (1.0 eq.) in tetrahydrofuran (0.1 M) were added N, N- diisopropylethylamine (3.0 eq.), 50 wt.% propylphosphonic anhydride solution in ethyl acetate (1.4 eq.) and the amine (1 eq.) then the mixture was stirred at room temperature until completion of the reaction. The crude mixture was concentrated under reduced pressure and the residues were purified by silica gel column chromatography or reverse phase column chromatography to afford the expected amide. General Procedure 6C: To a stirred solution of carboxylic acid (1.3 eq.) and amine (1.0 eq.) in N,N- dimethylformamide were added N,N-diisopropylethylamine (8.0 eq.), benzotriazole-1-yl-oxy- tris-(dimethylamino)-phosphoniumhexafluorophosphate (2.5 eq.) and the mixture was stirred at room temperature until completion of the reaction. The crude mixture was partitioned between dichloromethane and water, the layers were separated and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography or reverse phase column chromatography to afford the expected amide. General Procedure 6D: To a stirred solution of carboxylic acid (1.0 eq.) in N,N-dimethylformamide (0.1 M) were added N,N-diisopropylethylamine (2.0 eq.), 2-(1H-Benzotriazole-1-yl)-1,1,3,3- tetramethylaminium tetrafluoroborate (1.3 eq.) and the amine (1 eq.) then the mixture was stirred to room temperature until completion of the reaction. The mixture was dissolved with water and dichloromethane and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography or reverse phase column chromatography to afford the expected amide. General Procedure 7: Alkene hydrogenation General Procedure 7A: The alkene (1.0 eq.) was dissolved in methanol (0.3 M) and the system was purged with argon.20 wt.% palladium hydroxide on carbon was added (20 wt.% / alkene) and the mixture was stirred at room temperature under hydrogen (1 atm.) until completion of the reaction. The mixture was filtered through a short pad of celite and concentrated under reduced pressure. The residues were purified by silica gel column chromatography to give the corresponding product. General Procedure 7B: To a stirred solution of the alkene (1.0 eq.) in methanol (0.2 M) were added ammonium formate (1.2 eq.), 10 wt.% palladium on carbon (10 wt. % / alkene) and the mixture was heated to reflux until completion of the reaction. The mixture was filtered through a short pad of celite and concentrated under reduced pressure. The residues were purified by silica gel column chromatography to give the corresponding product. General Procedure 8: performed in a 4.0 mL vial using a total reaction volume of 1.33 mL with a 113 mM reaction concentration and using 150 µmol of bromides (1.0 eq.) and 180 µmmol of boronates (1.2 eq.). The vials were charged in a glovebox using the following conditions and order: Bromides: 0.15 M in N,N-dimethylformamide, evaporated in Genevac Boronates: 0.15 M in N,N-dimethylformamide, evaporated in Genevac Ligand: 0.02 M in toluene, evaporated in Genevac Pd-source: 0.1 M in acetone evaporated passively Solvent: 1,4-dioxane Base: 2 M in water, part of reaction solvent The vials were sealed and heated to 80 °C until completion of the reaction. The reaction mixtures were transferred to 1 µm GF filter cartridges using N,N-dimethylformamide (1.00 mL). Filters were rinsed with additional N,N-dimethylformamide (1.00 mL). The filtration was done into 4 mL vials by centrifugation in Genevac Filtrates were evaporated in Genevac "high BP, 75 ˚C" for 8 hours and the residual solvent was evaporated by freeze-drying at high vacuum. Step b: To the dried residue after Genevac was added 30.0 eq. trifluoroacetic acid as a 25% solution in dichloromethane at room temperature and the mixture were stirred at room temperature until completion fo the reaction. The mixture was transferred to 0.7 µm GF 96-filter plate using 1.00 mL of N,N-dimethylformamide. The filters were washed with 0.300 mL of N,N- dimethylformamide. The solutions were purified by reverse phase column chromatography (water / acetonitrile / trifluoroacetic acid) to give the desired products after freeze-drying. General Procedure 9: Stock solutions: Amines (1.05 eq.) were diluted in N, N-dimethylformamide to reach a final concentration of 3.0 M. Acids (1.0 eq., 1.50 mmol) were dissolved with 1-[bis(dimethylamino)methylene]-1H-1,2,3- triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (1.2 eq.) at 70 ˚C. N, N- diisopropylethylamine (2.0 eq.) was also added for a complete pre-activation mix. Reaction procedure: Amine (1.05 eq.) in N, N-dimethylformamide (3.0 M) was mixed with pre-activated acid (1.05 eq., 1.50 mmol) and the mixture was stirred for 3 h at room temperature. The reaction was heated to 70 ˚C to dissolve the formed precipitate and the reaction mixture was filtered through 0.45 µm syringe filters using N, N-dimethylsulfoxide to wash the filters. The filtrate was purified by reverse phase chromatography (water / acetonitrile / trifluoroacetic acid) to give the desired amide.

[0002] INTERMEDIATES Intermediate 1: N-[2-[4-[(1R)-1- acid tert-butyl ester Step A: Preparation of 2-[(1R)-1-(4-bromophenyl)ethyl]isoindoline-1,3-quinone (1R)-1-(4-bromophenyl)ethanamine (98.9 g, 0.494 mol) and isobenzofuran-1,3-dione (73.2 g, 0.494 mol) were dissolved in acetic acid (1.78 L) and the mixture was stirred at reflux until completion of the reaction. The mixture was concentrated under reduced pressure to reach 500 mL. Water was added and the resulting suspension was filtered to give 2-[(1R)-1-(4- bromophenyl)ethyl]isoindoline-1,3-quinone (147 g, 0.445 mol). tetramethyl-1,3,2-dioxaborolan-2- To a stirred and degassed solution of 2-[(1R)-1-(4-bromophenyl)ethyl]isoindoline-1,3- quinone (147 g, 0.445 mol) in 1,4-dioxane (2.21 L) were added 4,4,5,5-tetramethyl-2- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (124 g, 0.490 mol), [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (1:1) (9.09 g, 0.0111 mol) and potassium acetate (87.4 g, 0.891 mol) and the mixture was stirred at 90 °C until completion of the reaction. The mixture was cooled to room temperature and filtered through a short pad of celite. The mixture was concentrated under reduced pressure and the residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 2-[(1R)-1-[4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]isoindoline-1,3-quinone (109 g, 0.289 mol). 1H NMR (500 MHz, dmso-d6) δ ppm 7.9-7.81 (m, 4H), 7.64 (m, 2H), 7.39 (m, 2H), 5.47 (q, 1H), 1.82 (d, 3H), 1.26 (s, 12H). Step C: Preparation of N-[2-bromo-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester To a stirred solution of [2-bromo-4-(trifluoromethyl)phenyl]methanamine (5.00 g, 19.7 mmol) and triethylamine (6.86 mL, 49.2 mmol) in dichloromethane (70 mL), was added di- tert-butyl dicarbonate (5.58 g, 25.6 mmol) and the mixture was stirred at room temperature. After completion of the reaction, the mixture was dissolved in water and the aqueous layer was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give N-[2-bromo-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (6.80 g, 19.0 mmol). Step D: Preparation of N-[2-[4-[(1R)-1-phthalimidoethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-phthalimidoethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 2B using N-[2-bromo-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (12.1 g, 34.2 mmol) and 2-[(1R)-1-[4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl]isoindoline-1,3-quinone (15.5 g, 41.1 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give N-[2-[4-[(1R)-1-phthalimidoethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (15.5 g, 29.5 mmol). Step E: Preparation of Intermediate 1 Intermediate 1 was prepared according to General Procedure 1 using N-[2-[4-[(1R)-1- phthalimidoethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (2.25 g, 4.29 mmol) and hydrazine (1.77 mL, 21.4 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / ethanol / ammoniac) to give Intermediate 1 (1.55 g, 3.93 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 7.74 (br d, 1H), 7.59 (br d, 1H), 7.47 (m, 4H), 7.33 (br d, 2H), 4.13 (br d, 2H), 4.05 (q, 1H), 1.89 (br s, 2H), 1.36 (m, 9H), 1.29 (d, 3H). Intermediate 2: oxetane-3-carboxylate;sodium hydride   Intermediate 2 was prepared according to General Procedure 4A using methyl oxetane-3- carboxylate (2.52 g, 21.7 mmol) to give Intermediate 2 (2.69 g, 21.5 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. 1H NMR (400 MHz, dmso-d6) δ ppm 4.55 (m, 4H), 3.28 (m, 1H). Intermediate 3: 5-piperazinonicotinic acid methyl ester   Step A: Preparation of 4-(5-carbomethoxy-3-pyridyl)piperazine-1-carboxylic acid tert-butyl ester 4-(5-carbomethoxy-3-pyridyl)piperazine-1-carboxylic acid tert-butyl ester was prepared according to a modified General Procedure 5 using methyl 5-bromopyridine-3-carboxylate (5.00 g, 23.1 mmol), cesium carbonate (15.1 g, 46.3 mmol, 3.0 eq.) and tert-butyl piperazine- 1-carboxylate (5.17 g, 27.8 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 4-(5-carbomethoxy-3-pyridyl)piperazine-1- carboxylic acid tert-butyl ester (4.79 g, 13.4 mmol). Step B: Preparation of Intermediate 3 Intermediate 3 was prepared according to General Procedure 3A using 4-(5-carbomethoxy-3- pyridyl)piperazine-1-carboxylic acid tert-butyl ester (500 mg, 1.56 mmol) and trifluoroacetic acid (15.6 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Intermediate 3 (344 mg, 1.55 mmol). Intermediate 4: tert-butyl N-[[2-[4-[(1R)-1-[(4-bromopyridine-2- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate Step A: Preparation of lithium 4-bromopyridine-2-carboxylate Lithium 4-bromopyridine-2-carboxylate was prepared according to General Procedure 4B using methyl 4-bromopyridine-2-carboxylate (500 mg, 2.32 mmol, 1.0 eq.) to give lithium 4- bromopyridine-2-carboxylate (481 mg, 2.31 mmol). The compound was engaged into the next step without further purification. Step B: Preparation of Intermediate 4 Intermediate 4 was prepared according to General Procedure 6A using Intermediate 1 (900 mg, 2.28 mmol, 1.0 eq.), lithium 4-bromopyridine-2-carboxylate (475 mg, 2.28 mmol, 1.0 eq.) and 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylammonium tetrafluoroborate (952 mg, 2.97 mmol, 1.3 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give Intermediate 4 (1.12 g, 1.94 mmol). Intermediate 5: 4-(1-Acetylpyrrolidin-3-yl)-2,3-dihydro-1,4-benzoxazine-6-carboxylic acid Step A: Synthesis of methyl 4-(1-(tert-butoxycarbonyl) pyrrolidin-3-yl)-3,4-dihydro-2H- benzo[b][1,4]oxazine-6-carboxylate tert-Butyl 3-oxopyrrolidine-1-carboxylate (2.88 g, 15.5 mmol, 2.0 eq.) and trifluoroacetic acid (594 µL, 7.76 mmol, 1.0 eq.) were added to a stirred solution of methyl 3,4-dihydro-2H- benzo[b][1,4]oxazine-6-carboxylate (1.50 g, 7.76 mmol, 1.0 eq.) in dichloromethane (25 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 1 h and then sodium borohydride (1.47 g, 38.8 mmol, 5.0 eq.) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with an aqueous sodium bicarbonate solution and extracted with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude residues was purified by silica gel column (petroleum ether / ethyl acetate) to give methyl 4-(1- (tert-butoxycarbonyl)pyrrolidin-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylate (2.00 g, 5.32 mmol). Step B: Preparation of methyl 4-(pyrrolidin-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6- carboxylate Trifluoroacetic acid (10 mL, 131 mmol, 24 eq.) was added to a stirred solution methyl 4-(1- (tert-butoxycarbonyl) pyrrolidin-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylate (2.00 g, 5.52 mmol, 1.0 eq.) in dichloromethane (10 mL) at 0 °C. The reaction mixture was warmed up to room temperature and until completion of the reaction. The reaction mixture was quenched with saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulphate, filtered and concentrated under reduced pressure to give the crude methyl 4- (pyrrolidin-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylate (1.40 g, 5.04 mmol). C: Preparation of methyl 4-(1-acetylpyrrolidin-3-yl)-3,4-dihydro-2H- benzo[b][1,4]oxazine-6-carboxylate Triethylamine (1.49 mL, 10.7 mmol, 2.0 eq.) and acetyl chloride (570 µL, 8.01 mmol, 1.5 eq.) were added to a stirred solution of methyl 4-(pyrrolidin-3-yl)-3,4-dihydro-2H- benzo[b][1,4]oxazine-6-carboxylate (1.40 g, 5.34 mmol, 1.0 eq.) in dichloromethane (15 mL) at 0 °C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with a saturated aqueous sodium bicarbonate solution and the organic layer was extracted with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulphate, filtered, and concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (petroleum ether / ethyl acetate) to give methyl 4-(1-acetylpyrrolidin-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylate (1.08 g, 3.53 mmol). Step D: Preparation of Intermediate 5 Lithium hydroxide (340 mg, 14.1 mmol, 4.0 eq.) was added to a stirred solution of methyl 4- (1-acetylpyrrolidin-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylate (1.08 g, 3.53 mmol, 1.0 eq.) in a 9:1 THF / methanol mixture (22 mL) at room temperature. The reaction media was warmed up to 70 °C and stirred overnight. The reaction mixture was diluted with ice cold water (25 mL) and neutralized by addition of a 1.5 M aqueous hydrogen chloride solution. The organic layer was extracted with dichloromethane, washed with brine, dried over sodium sulphate, filtered, and concentrated under reduced pressure to give the crude Intermediate 5 (1.00 g, 3.30 mmol).1H NMR (300 MHz, DMSO-d6) (mixture of rotamers) δ 12.43 (s, 1H), 7.40 - 7.38 (m, 1H), 7.22 (dd, J = 8.1, 1.8 Hz, 1H), 6.77 (dd, J = 8.4, 1.5 Hz, 1H), 4.59 − 4.41 (m, 1H), 4.23 (t, J = 4.2 Hz, 2H), 3.73 - 3.45 (m, 3H), 3.28 − 3.24 (m, 3H), 2.16 − 2.11 (m, 1H), 2.07 − 2.02 (m, 1H), 1.97 (s, 3H).291. [M+H]+ = 291.1. Intermediate 6: 2-[ -1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)phenyl]ethyl] 1,3-dione Step A: Preparation of 2-[(1R)-1-(4-bromophenyl)ethyl]isoindole-1,3-dione To a stirred solution of phthalic anhydride (760 g, 5.13 mol, 1.1 eq.) and acetic acid (4.89 L, 83.6 mol, 17 eq.) was added (1R)-1-(4-bromophenyl)ethanamine (978 g, 4.89 mol, 1.0 eq.) at room temperature and the mixture was heated to 120 °C for 5 hours and the mixture was cooled to room temperature until full conversion of the starting material. Water was added at the mixture. Then, the mixture was filtered and the solid was washed with water and oven- dried to afford 2-[(1R)-1-(4-bromophenyl)ethyl]isoindole-1,3-dione (1.52 kg, 4.59 mol). Step B: Preparation of Intermediate 6 Under nitrogen, a solution of 2-[(1R)-1-(4-bromophenyl)ethyl]isoindoline-1,3-dione (906 g, 2.74 mol, 1.0 eq.), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi-1,3,2-dioxaborolane (766 g, 3.02 mol, 1.1 eq.), potassium acetate (539 g, 5.49 mol, 2.0 eq.) and [1,1′- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (100 g, 137 mmol, 0.05 eq.) in 1.4- dioxane (0.30 M) was heated to 100 °C until completion of the reaction. The mixture was filtered, and the mixture was concentrated under reduced pressure. Then, the residues were dissolved in toluene and N-Acetyl-L-cysteine (0.75 M) was added. The mixture was filtered and then, concentrated under reduced pressure. The residues were purified by silica gel column chromatography (toluene / ethyl acetate) to give Intermediate 6 (804 g, 2.13 mol). Intermediate 9: 1,4λ5- 4-oxide Step A: Preparation of 4-hydroxy-1,4λ5-oxaphosphinane 4-oxide Under Argon, a mixture of bis(trimethylsilyl)amine (194 mg, 120 mmol, 2.0 eq.) and ammonium hypophosphite (5.00 g, 60.2 mmol, 1.0 eq.) was heated to 120 °C for 4 hours. Then, 1-bromo-2-(2-bromoethoxy)ethane (14.0 g, 60.2 mmol, 1.0 eq.) was added and the mixture was heated to 120 °C until completion of the reaction. The reaction mixture was allowed to cool at room temperature, then the mixture was dissolved in ethanol. The reaction mixture was heated to reflux for 1 hour and the reaction mixture was allowed to cool to room temperature. The mixture was filtered, washed with dichloromethane and the mixture was concentrated under reduce pressure. The crude residues were purified by reverse phase chromatography (water / acetonitrile / trifluoroacetic acid) to give 4-hydroxy-1,4λ5- oxaphosphinane 4-oxide (942 mg, 6.92 mmol). Step B: Preparation of 4-chloro-1,4λ5-oxaphosphinane 4-oxide Under argon, to a stirred solution of 4-hydroxy-1,4λ5-oxaphosphinane 4-oxide (400 mg, 2.94 mmol, 1.0 eq.) in dichloromethane (0.36 M) at 0°C, was added oxalyl dichloride (1.49 g, 11.8 mmol, 4.0 eq.). The reaction mixture was stirred at room temperature until completion of the reaction. The mixture was concentrated under reduce pressure. The residues were dissolved in toluene and the mixture was concentrated under reduced pressure to give 4-chloro-1,4λ5- oxaphosphinane 4-oxide (447 mg, 2.90 mmol). The compound was engaged into the next step without further purification. Step C: Preparation of 1,4λ5-oxaphosphinane 4-oxide Under argon, to a stirred solution of 4-chloro-1,4λ5-oxaphosphinane 4-oxide (447 mg, 2.89 mmol, 1.0 eq.) in dichloromethane (0.8 M) at -70°C, was added a solution of 1 M diisobutylaluminum hydride in tetrahydrofuran (2.40 g, 3.19 mmol, 1.1 eq.) dissolved in a minimum of dichloromethane. The reaction mixture was stirred at -70 °C for 2 hours. Then, the mixture was quenched with methanol at -70 °C and the mixture was stirred for few minutes. The mixture was allowed to reach 0 °C and a solution of acetic acid (2.49 mL, 4.35 mmol, 1.5 eq.) in water (0.1 M) was added. Then, the mixture was stirred and allowed to reach room temperature. The mixture was dissolved with water and dichloromethane and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give Intermediate 9 (263 mg, 2.19 mmol). The compound was engaged into the next step without further purification. Intermediate 10: tert-butyl N-[[2-[4-[(1R)-1-[(5-bromopyridine-3- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate Intermediate 10 was prepared according to a modified General Procedure 6B using Intermediate 1 (1.00 g, 2.00 mmol) and 5-bromopyridine-3-carboxylic acid (500 mg, 2.00 mmol) in tetrahydrofuran (0.3 M). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give Intermediate 10 (1.30 g, 2.00 mmol). Intermediate 11: tert-butyl N-[[2-[4-[(1R)-1-[(6-chloropyrazine-2- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate Intermediate 11 was prepared according to a modified General Procedure 6B using Intermediate 1 (1.24 g, 3.15 mmol) and 6-chloropyrazine-2-carboxylic acid (500 mg, 3.15 mmol) in tetrahydrofuran (0.3 M). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give Intermediate 11 (1.12 g, 1.88 mmol). Intermediate 13: tert-butyl N-[[2-[4-[(1R)-1-[(4-bromopyridine-2- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate Intermediate 13 was prepared according to General Procedure 6B using Intermediate 1 (2.90 g, 7.40 mmol) and 4-bromopyridine-2-carboxylic acid (1.50 g, 7.40 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to give Intermediate 13 (2.30 g, 4.00 mmol). Intermediate 15: tert-butyl N-[[2-[4-[ -1-[(2-bromo-1,3-thiazole-5- carbonyl)amino]ethyl]phenyl]-4- phenyl]methyl]carbamate To a stirred solution of 2-bromothiazole-5-carboxylic acid (600 mg, 2.88 mmol) and N,N- Diisopropylethylamine (1.51 mL, 8.65 mmol) in N,N-dimethylformamide (2.00 mL) was added tert-butyl (R)-((4'-(1-aminoethyl)-5-(trifluoromethyl)-[1,1'-biphenyl]-2- yl)methyl)carbamate (1.13 g, 2.88 mmol) followed by benzotriazol-1- yloxytris(dimethylamino)phosphonium hexafluorophosphate (2.55 g, 5.77 mmol) at room temperature. After completion of the reaction, ethyl acetate was added and the mixture was filtered on celite bed. The filtrate was concentrated under reduced pressure to give without further purification tert-butyl (R)-((4'-(1-(2-bromothiazole-5-carboxamido)ethyl)-5- (trifluoromethyl)-[1,1'-biphenyl]-2-yl)methyl)carbamate (840 mg, 1.36 mmol). Intermediate 16: tert-butyl N-[[4-(difluoromethyl)-2-(4,4,5,5-tetraethyl-1,3,2- dioxaborolan-2-yl)phenyl]methyl]carbamate Step A: Preparation of 2-bromo-4-(difluoromethyl)benzonitrile 2-bromo-4-(difluoromethyl)benzonitrile 2-bromo-4-formyl-benzonitrile (5.00 g, 23.8 mmol, 1.0 eq.) was dissolved in dichloromethane (119 mL) and the system was purged with nitrogen and the mixture was cooled to 0 °C. Then, N-ethyl-N-(trifluoro- 4-sulfanyl)ethanamine (4.60 g, 3.77 mL, 28.6 mmol, 1.2 eq.) was added dropwise and the mixture was stirred at room temperature until completion of the reaction. The reaction was quenched with water and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography using ethyl acetate in heptane to give 2-bromo-4-(difluoromethyl)benzonitrile (4.86 g, 20.9 mmol). Step B: Preparation of 4-(difluoromethyl)-2-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2- yl)benzonitrile 4-(Difluoromethyl)-2-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)benzonitrile was prepared according to General Procedure 2A using 2-bromo-4-(difluoromethyl)benzonitrile (1.05 g, 4.53 mmol) and 4,4,5,5-tetraethyl-2-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-1,3,2- dioxaborolane(1.82 g, 4.98 mmol). The crude residues were purified by silica gel column chromatography (ethyl acetate / heptane) to give 4-(difluoromethyl)-2-(4,4,5,5-tetraethyl-1,3,2- dioxaborolan-2-yl)benzonitrile (825 mg, 2.46 mmol). Step C: Preparation of Intermediate 16 To a stirred solution of 4-(difluoromethyl)-2-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2- yl)benzonitrile (815 mg, 2.43 mmol, 1.0 eq.) in anhydrous methanol (15.0 mL)at 0 °C, were added di-tert-butyl dicarbonate (1.06 g, 4.86 mmol, 2.0 eq.), nickel chloride (57.8 mg, 243 µmol, 0.10 eq.) and sodium borohydride (644 mg, 17.0 mmol, 7.0 eq.) was then added in small portions over 30 min. The resulting reaction mixture was allowed to reach room temperature and left to stir for a further 1 h, at which point N'-(2-aminoethyl)ethane-1,2- diamine (251 mg, 2.43 mmol, 1.0 eq.) was added and the mixture was stirred at room temperature until completion of the reaction. The mixture was concentrated under reduced pressure and the residues were dissolved in ethyl acetate and the organic layer was washed with saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography using ethyl acetate in heptane as an eluent the crude expected solid product, that was washed with diethyl ether to give Intermediate 16 (130 mg, 383 µmol). Intermediate 17: tert-butyl N-[[3-chloro-2-(4,4,5,5- 1,3,2-dioxaborolan-2-yl)- A solution of [6-[(tert-butoxycarbonylamino)methyl]-2-chloro-3-(trifluoromethyl)phenyl] trifluoromethanesulfonate (1.75 g, 3.82 mmol, 1.0 eq.) in 1,4-dioxane (14.0 mL) was degassed for 10 min under nitrogen.4,4,5,5-Tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3,2-dioxaborolane (2.43 g, 9.56 mmol, 2.5 eq.), potassium acetate (1.69 g, 17.2 mmol, 4.5 eq.), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (420 mg, 573 µmol, 0.15 eq.) were added and the mixture was heated to 80 °C until completion of the reaction. Water and ethyl acetate were added and the precipitated solid was filtered over a short pad of celite. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography using toluene in dichloromethane to give Intermediate 17 (1.35 g, 3.10 mmol). Intermediate 18: tert-butyl N-[[5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 4-(trifluoromethyl)phenyl]methyl]carbamate Step A: Preparation of 2-bromo-5-fluoro-4-(trifluoromethyl)benzamide 7 N Ammonia in methanol (30.0 mL, 210 mmol, 23 eq.) was added at room temperature to methyl 2-bromo-5-fluoro-4-(trifluoromethyl)benzoate (2.70 g, 9.00 mmol, 1.0 eq.) in a sealed tube and the mixture was heated to reflux until complete conversion. The reaction mixture was concentrated under reduced pressure to give 2-bromo-5-fluoro-4- (trifluoromethyl)benzamide (2.60 g, 9.09 mmol), that was used in the next step without further purification. 5-fluoro-4- To a solution of 2-bromo-5-fluoro-4-(trifluoromethyl)benzamide (2.60 g, 9.09 mmol, 1.0 eq.) in tetrahydrofuran (15.0 mL) was added 1 M borane tetrahydrofuran complex solution (27.3 mL, 27.3 mmol, 3.0 eq.) at room temperature and the reaction mixture was heated to reflux until completion of the reaction. The reaction was quenched carefully by adding dropwise conc.37 wt.% hydrogen chloride (2.00 mL) and the mixture was heated to reflux for another 2 h before being cooled down to room temperature and basified to pH~10 by adding sat. sodium carbonate solution. The reaction was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to give the crude ([2-bromo-5-fluoro-4-(trifluoromethyl)phenyl]methanamine (2.40 g, 8.80 mmol). ([2- bromo-5-fluoro-4-(trifluoromethyl)phenyl]methanamine (2.40 g, 8.80 mmol, 1.0 eq.)) was dissolved in dichloromethane (15.0 mL) and tert-butoxycarbonyl tert-butyl carbonate (2.00 g, 9.30 mmol, 1.1 eq.) was added. The solution was stirred at room temperature until completion of the reaction, before adding ethanolamine (0.330 mL). After further stirring at room temperature for 1 h, the reaction mixture was partitioned between dichloromethane and water. The organic layer was isolated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residues were purified by silica gel column chromatography using dichloromethane in heptane as an eluent to give tert-butylN-[[2-bromo- 5-fluoro-4-(trifluoromethyl)phenyl]methyl]carbamate (2.60 g, 7.00 mmol). Step C: Preparation of Intermediate 18 To a mixture of tert-butyl N-[[2-bromo-5-fluoro-4-(trifluoromethyl)phenyl]methyl]carbamate (2.50 g, 6.72 mmol,1.0 eq.) and 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.88 g, 7.39 mmol, 1.10 eq.) in 1,4-dioxane (22.4 mL) were added potassium acetate (857 mg, 8.73 mmol, 1.3 eq.)and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (165 mg, 202 µmol, 0.030 eq.) and the mixture was degassed under argon. The mixture was heated to reflux until completion of the reaction. The reaction mixture was diluted with ethyl acetate and filtered over a short pad of celite. Water was added and the layers were separated. The aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography using dichloromethane and ethyl acetate as an eluent to give Intermediate 18 (2.50 g, 6.00 mmol). Intermediate 19: tert-butyl N-[[3-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-5- (trifluoromethyl)-2-pyridinyl]methyl]carbamate Step A: Preparation of 3-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-5- (trifluoromethyl)pyridine-2-carbonitrile 3-(4,4,5,5-Tetraethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)pyridine-2-carbonitrile 3- bromo-5-(trifluoromethyl)pyridine-2-carbonitrile (9.00 g, 35.9 mmol, 1.0 eq.), 4,4,4',4',5,5,5',5'-octaethyl-2,2'-bi(1,3,2-dioxaborolane) (13.4 g, 36.6 mmol, 1.0 eq.), potassium acetate (10.6 g, 108 mmol, 3.0 eq.) and [1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (519 mg, 1.08 mmol, 0.030 eq.) were dissolved in 1,4-dioxane (108 mL). The mixture was degassed and purged with argon and the mixture was heated to reflux until completion of the reaction. The mixture was concentrated under reduced pressure and the residues were purified by silica gel column chromatography using dichloromethane to give 3-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-5- (trifluoromethyl)pyridine-2-carbonitrile (12.5 g, 34.6 mmol). (4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-2- 1 M Diisobutylaluminum hydride solution in tetrahydrofuran (103 mL, 130 mmol, 3.0 eq.) was slowly added at 0 °C to a solution of 3-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-5- (trifluoromethyl)pyridine-2-carbonitrile (12.4 g, 34.3 mmol, 1.0 eq.) in 1,2-dichloroethane (137 mL)and the mixture was stirred at 5 °C until completion of the reaction. The reaction was quenched by adding saturated ammonium chloride and 2 N sodium hydroxide at 0 °C. The aqueous layer was extracted with dichloromethane and the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give [3- (4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-2-pyridinyl]methanamine (14.0 g, 35.2 mmol) that was used in the next step without further purification. Step C: Preparation of Intermediate 19 Tert-butoxycarbonyl tert-butyl carbonate (7.68 g, 35.2 mmol, 1.0 eq.) was added to a mixture of [3-(4,4,5,5-tetraethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-2- pyridinyl]methanamine (14.0 g, 35.2 mmol, 1.0 eq.), triethylamine (4.90 mL, 35.2 mmol, 1.0 eq.) and dichloromethane (141 mL) and the reaction mixture was stirred overnight at room temperature. The reaction mixture was partitioned between sat. ammonium chloride and dichloromethane. The layers were separated, and the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography using ethyl acetate and dichloromethane as an eluent to give Intermediate 19 (12.9 g, 28.1 mmol).

[0003] EXAMPLES Example 1: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-pyrimidine-4-carboxamide   Step A: Preparation of 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid 2-(3,6-Dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid was prepared according to a modified General Procedure 2A using methyl 2-bromopyrimidine-4-carboxylate (169 g, 777 mmol), potassium carbonate (495 g, 2.33 mol, 3.0 eq) and 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester (172 g, 816 mmol). After completion of the reaction, the reaction mixture was filtered over Clarcel® and washed with dioxane (338 mL). The mixture was concentrated under reduced pressure and dichloromethane and water were added. The layers were separated. Dichloromethane was added to the aqueous layer and pH was decreased with concentrated hydrogen chloride to pH < 1. The precipitated solid was filtered to give the crude 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid, which was engaged into the next step considering a quantitative yield. Step B: Preparation of methyl 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate A stirred solution of 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid (144 g, 0.698 mol, 1 equiv.) and 95 wt.% sulfuric acid (39.2 mL, 0.698 mol, 1 equiv.) in methanol (0.72 L) was heated to reflux until completion of the reaction. The reaction mixture was cooled to room temperature and filtered through a fritted funnel. Water (0.5 L) and dichloromethane (0.5 L) were added to the solid and potassium carbonate was added until a basic pH was reached. The layers were separated and the organic layer was concentrated under reduced pressure to give methyl 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4- carboxylate (88.0 g, 0.400 mol). Step C: Preparation of methyl 2-tetrahydropyran-4-ylpyrimidine-4-carboxylate A stirred solution of methyl 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate (88.0 g, 0.400 mol, 1 equiv.) and 5 wt.% palladium on calcium carbonate (3.52 g, 33.1 mmol, 0.04 mol%) in methanol (1.32 L) was saturated with hydrogen and stirred until completion of the reaction. The reaction mixture was filtered through a short pad of Clarcel®, and the mixture was concentrated to 7 L / Kg to be engaged into the next step, without further purification. Step D: Preparation of 2-tetrahydropyran-4-ylpyrimidine-4-carboxylic acid 2-tetrahydropyran-4-ylpyrimidine-4-carboxylic acid was prepared according to a modified General Procedure 4A using methyl 2-tetrahydropyran-4-ylpyrimidine-4-carboxylate (88.8 g, 400 mmol), aqueous 2 M sodium hydroxide (0.800 mol, 2.0 eq.). After completion of the reaction, concentrated 37 wt.% hydrogen chloride (67.3 mL, 0.800 mol) was added over 20 minutes and the mixture was stirred for 50 minutes at room temperature before being filtered through a fritted funnel. The solids were washed with water and dried to give 2- tetrahydropyran-4-ylpyrimidine-4-carboxylic acid (57.4 g, 276 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 13.8 (br s, 1H), 9.01 (d, 1H), 7.82 (d, 1H), 3.95 (m, 2H), 3.48 (br t, 2H), 3.16 (m, 1H), 1.85 (m, 4H). Step E: Preparation of N-[2-[4-[(1R)-1-[(2-tetrahydropyran-4-ylpyrimidine-4- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(2-tetrahydropyran-4-ylpyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6B using Intermediate 1 (250 mg, 0.634 mmol) and 2-tetrahydropyran-4- ylpyrimidine-4-carboxylic acid (132 mg, 0.634 mmol) to give the crude N-[2-[4-[(1R)-1-[(2- tetrahydropyran-4-ylpyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (370 mg, 0.633 mmol). Example 1 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(2- tetrahydropyran-4-ylpyrimidine-4-carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (370 mg, 0.633 mmol) and trifluoroacetic acid (6.33 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (water / acetonitrile / trifluoroacetic acid) to give Example 1 (128 mg, 0.264 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.15 (d, 1H), 9 (d, 1H), 7.83 (m, 2H), 7.71 (dd, 1H), 7.52 (d, 2H), 7.44 (d, 1H), 7.39 (d, 2H), 5.28 (quin, 1H), 3.98 (dt, 2H), 3.67 (s, 2H), 3.49 (m, 2H), 3.2 (m, 1H), 1.93 (m, 6H), 1.61 (d, 3H). [M+H]+=485.2132 Step A: Preparation of 4-(2-carbomethoxy-4-pyridyl)piperazine-1-carboxylic acid tert-butyl ester 4-(2-carbomethoxy-4-pyridyl)piperazine-1-carboxylic acid tert-butyl ester was prepared according to a modified General Procedure 5 using methyl 4-bromopyridine-2-carboxylate (1.00 g, 4.63 mmol), cesium carbonate (3.02 g, 9.26 mmol, 3.0 eq.) and tert-butyl piperazine- 1-carboxylate (1.03 g, 5.55 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 4-(5-carbomethoxy-3-pyridyl)piperazine-1- carboxylic acid tert-butyl ester (0.823 g, 2.31 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.27 (d, 1H), 7.44 (d, 1H), 7.01 (dd, 1H), 3.84 (s, 3H), 3.42 (m, 8H), 1.42 (s, 9H). Step B: Preparation of 4-piperazinopicolinic acid methyl ester 4-piperazinopicolinic acid methyl ester was prepared according to General Procedure 3A using 4-(2-carbomethoxy-4-pyridyl)piperazine-1-carboxylic acid tert-butyl ester (823 mg, 2.56 mmol) and trifluoroacetic acid (25.6 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 4- piperazinopicolinic acid methyl ester (494 mg, 2.23 mmol). Step C: Preparation of 4-[4-(oxetane-3-carbonyl)piperazino]picolinic acid methyl ester 4-[4-(oxetane-3-carbonyl)piperazino]picolinic acid methyl ester was prepared according to General Procedure 6A using 4-piperazinopicolinic acid methyl ester (494 mg, 2.23 mmol) and Intermediate 2 (277 mg, 2.23 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[4-[4-(oxetane-3- carbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (680 mg, 2.23 mmol). Step D: Preparation of lithium;4-[4-(oxetane-3-carbonyl)piperazino]picolinate lithium;4-[4-(oxetane-3-carbonyl)piperazino]picolinate was prepared according to General Procedure 4B using 4-[4-(oxetane-3-carbonyl)piperazino]picolinic acid methyl ester (680 mg, 2.23 mmol) to give lithium;4-[4-(oxetane-3-carbonyl)piperazino]picolinate (662 mg, 2.23 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step E: Preparation of N-[2- (oxetane-3-carbonyl)piperazino]picolinoyl] amino]ethyl]phenyl]-4- carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-[4-(oxetane-3-carbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (800 mg, 2.03 mmol) and lithium;4-[4-(oxetane-3- carbonyl)piperazino]picolinate (603 mg, 2.03 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[4- [4-(oxetane-3-carbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (846 mg, 1.27 mmol). Step F: Preparation of Example 2 Example 2 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[4- (oxetane-3-carbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (846 mg, 1.27 mmol) and trifluoroacetic acid (12.7 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (water / acetonitrile / trifluoroacetic acid) to give Example 2 (331 mg, 0.583 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.95 (d, 1H), 8.25 (d, 1H), 7.84 (d, 1H), 7.71 (br d, 1H), 7.49 (d, 2H), 7.44 (d, 2H), 7.36 (d, 2H), 7 (dd, 1H), 5.21 (quin, 1H), 4.69 (m, 4H), 4.17 (m, 1H), 3.67 (s, 2H), 3.61 (m, 2H), 3.41 (m, 4H), 3.34 (m, 2H), 2.16 (br s, 2H), 1.56 (d, 3H). [M+H]+=568.2540 -5- Step A: Preparation of 5-[4-(oxetane-3-carbonyl)piperazino]nicotinic acid methyl ester 5-[4-(oxetane-3-carbonyl)piperazino]nicotinic acid methyl ester was prepared according to General Procedure 6A using Intermediate 3 (344 mg, 1.55 mmol) and oxetane-3-carboxylic acid (159 mg, 1.55 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[4-(oxetane-3- carbonyl)piperazino]nicotinic acid methyl ester (474 mg, 1.55 mmol). lithium;5-[4-(oxetane-3-carbonyl)piperazino]nicotinate was prepared according to General Procedure 4B using 5-[4-(oxetane-3-carbonyl)piperazino]nicotinic acid methyl ester (474 mg, 1.55 mmol) to give lithium;5-[4-(oxetane-3-carbonyl)piperazino]nicotinate (461 mg, 1.55 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- (oxetane-3-carbonyl)piperazino]nicotinoyl] amino]ethyl]phenyl]-4- carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[4-(oxetane-3-carbonyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (600 mg, 1.52 mmol) and lithium;5-[4-(oxetane-3- carbonyl)piperazino]nicotinate (452 mg, 1.52 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[5- [4-(oxetane-3-carbonyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (720 mg, 1.08 mmol). Step D: Preparation of Example 3 Example 3 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[4- (oxetane-3-carbonyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (720 mg, 1.08 mmol) and trifluoroacetic acid (0.826 mL, 10.8 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase column chromatography (carbon dioxide / methanol / diethylamine) to give Example 3 (331 mg, 0.583 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.97 (d, 1H), 8.52 (d, 1H), 8.45 (d, 1H), 7.85 (d, 1H), 7.71 (m, 2H), 7.48 (m, 2H), 7.44 (d, 1H), 7.38 (d, 2H), 5.26 (quin, 1H), 4.7 (m, 4H), 4.18 (m, 1H), 3.68 (s, 2H), 3.65 (m, 2H), 3.34 (m, 2H), 3.26 (m, 4H), 1.98 (br d, 2H), 1.54 (d, 3H). [M+H]+=568.2535 Example 4: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- (3,6-dihydro-2H-pyran-4-yl)nicotinamide   Step A: Preparation of methyl 5-(3,6-dihydro-2H-pyran-4-yl)pyridine-3-carboxylate To a mechanically stirred reactor containing methyl 5-bromopyridine-3-carboxylate (150 g, 0.694 mol, 1.0 equiv.), 2-(3,6-dihydro-2H-pyran-5-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (175 g, 0.833 mol, 1.2 equiv.), potassium carbonate (288 g, 2.08 mol, 3.0 equiv.), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (30.5 g, 0.0410 mol, 0.060 equiv.) were added dioxane (1.20 L, 8 L / Kg) and water (0.30 L, 2 L / Kg). The reactor temperature was then set to 110 °C and the mixture was refluxed for 1 h. After completion of the reaction, the mixture was cooled to 20 °C and the reaction mixture was filtered over Clarcel® and washed with 1,4-dioxane. After concentration to dryness, the residues were dissolved into dichloromethane and water. The mixture was stirred and the layers were separated. The organic layer was filtered over a short pad of silica gel and was eluted with dichloromethane. The organic layer was washed with water and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to afford methyl 5-(3,6-dihydro-2H-pyran-4-yl)pyridine-3- carboxylate (116 g, 0.529 mol). Step B: Preparation of 5-(3,6-dihydro-2H-pyran-4-yl)nicotinic acid To a mechanically stirred reactor containing methyl 5-(3,6-dihydro-2H-pyran-4-yl)pyridine-3- carboxylate (116 g, 0.529 mol, 1.0 equiv.) in methanol (0.582 L, 5 L / Kg) at 5 °C, was added aqueous 30 wt.% sodium hydroxide (106 mL, 1.06 mol, 2.0 equiv.) over 30 minutes. After completion of the reaction, concentrated aqueous hydrochloric acid (89.4 mL, 1.06 mol, 2.0 equiv.) was added over 20 minutes, and the mixture was stirred for 30 minutes at room temperature. The suspension was filtered, and the cake mix was washed with water and was dried at 50 °C for 24 hours to obtain 5-(3,6-dihydro-2H-pyran-4-yl)nicotinic acid (107 g, 0.520 mol.1H NMR (400 MHz, dmso-d6) δ ppm 13.49 (m, 1H), 8.95 (d, 1H), 8.9 (d, 1H), 8.22 (t, 1H), 6.5 (br s, 1H), 4.25 (q, 2H), 3.84 (t, 2H), 2.53 (m, 2H). Step C: Preparation of N-[2-[4-[(1R)-1- (3,6-dihydro-2H-pyran-4- yl)nicotinoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-(3,6-dihydro-2H-pyran-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6A using Intermediate 1 (250 mg, 0.634 mmol) and 5-(3,6-dihydro-2H- pyran-4-yl)nicotinic acid (130 mg, 0.634 mmol) to give the crude N-[2-[4-[(1R)-1-[[5-(3,6- dihydro-2H-pyran-4-yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (368 mg, 0.633 mmol), which was used into the next step without further purification (considering a quantitative yield). Step D: Preparation of Example 4 Example 4 was prepared according to a modified General Procedure 3A using N-[2-[4-[(1R)- 1-[[5-(3,6-dihydro-2H-pyran-4-yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (368 mg, 0.633 mmol) and trifluoroacetic acid (0.485 mL, 6.33 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase column chromatography (acetonitrile / water / ammonium bicarbonate) to give Example 4 (227 mg, 0.471 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.08 (d, 1H), 8.95 (d, 1H), 8.82 (d, 1H), 8.26 (t, 1H), 7.85 (d, 1H), 7.71 (dd, 1H), 7.5 (d, 2H), 7.45 (s, 1H), 7.39 (d, 2H), 6.49 (br s, 1H), 5.27 (quin, 1H), 4.27 (q, 2H), 3.86 (t, 2H), 3.68 (s, 2H), 2.52 (br d, 2H), 2.07 (m, 2H), 1.56 (d, 3H). [M+H]+=482.2053 Example 5: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-3- morpholino-benzamide   Step A: Preparation of 3-morpholinobenzoic acid 3-morpholinobenzoic acid was prepared according to a modified General Procedure 4A using methyl 3-morpholinobenzoate (520 mg, 2.35 mmol). After adding aqueous 1 N hydrogen chloride (12.0 mL), the precipitate was filtered and dried to give 3-morpholinobenzoic acid (340 mg, 1.64 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 12.85 (br s, 1H), 7.45 (s, 1H), 7.38 (m, 1H), 7.34 (m, 1H), 7.2 (d, 1H), 3.75 (m, 4H), 3.14 (m, 4H). Step B: Preparation of N-[2-[4-[(1R)-1-[(3-morpholinobenzoyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(3-morpholinobenzoyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6A using Intermediate 1 (285 mg, 0.723 mmol) and 3-morpholinobenzoic acid (150 mg, 0.723 mmol), considering a quantitative yield. The product was used into the next step without further purification. Step C: Preparation of Example 5 Example 5 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(3- morpholinobenzoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (420 mg, 0.720 mmol) and trifluoroacetic acid (7.20 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase column chromatography (acetonitrile / water / ammonium bicarbonate) to give Example 5 (294 mg, 0.608 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.78 (d, 1H), 7.85 (d, 1H), 7.72 (dd, 1H), 7.48 (d, 2H), 7.46 (s, 1H), 7.43 (s, 1H), 7.37 (m, 3H), 7.32 (m, 1H), 7.11 (dd, 1H), 5.25 (quin, 1H), 3.76 (m, 4H), 3.71 (s, 2H), 3.16 (m, 4H), 1.54 (d, 3H). [M+H]+=484.2205 (δ=-0.3 ppm). Example 6: 5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]nicotinamide   Step A: Preparation of 5-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester 5-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester was prepared according to General Procedure 2A using methyl 5-bromopyridine-3-carboxylate (5.00 g, 23.1 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6- dihydro-2H-pyridine-1-carboxylate (8.59 g, 27.7 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-(1-tert- butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester (7.18 g, 22.6 mmol). Step B: Preparation of 5-(1,2,3,6-tetrahydropyridin-4-yl)nicotinic acid methyl ester 5-(1,2,3,6-tetrahydropyridin-4-yl)nicotinic acid methyl ester was prepared according to General Procedure 3A using 5-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester (500 mg, 1.57 mmol) and trifluoroacetic acid (1.20 mL, 15.7 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 5-(1,2,3,6-tetrahydropyridin-4-yl)nicotinic acid methyl ester (342 mg, 1.57 mmol). Step C: Preparation of 5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester Acetyl chloride (0.152 mL, 2.03 mmol) was added to a solution of 5-(1,2,3,6- tetrahydropyridin-4-yl)nicotinic acid methyl ester (402 mg, 1.84 mmol) and N, N- triethylamine (0.514 mL, 3.68 mmol) in acetonitrile (10.0 mL). After completion of the reaction, the mixture was concentrated under reduced pressure. Water was added and the aqueous layer was extracted with dichloromethane. The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester (479 mg, 1.84 mmol). Step D: Preparation of lithium;5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinate lithium;5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinate was prepared according to General Procedure 4B using 5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester (479 mg, 1.84 mmol) to give lithium;5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinate (464 mg, 1.84 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step E: Preparation of N-[2-[4-[(1R)-1- (1-acetyl-3,6-dihydro-2H-pyridin-4- yl)nicotinoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6A using Intermediate 1 (250 mg, 0.634 mmol) and lithium;5-(1-acetyl- 3,6-dihydro-2H-pyridin-4-yl)nicotinate (160 mg, 0.634 mmol) to give the crude N-[2-[4- [(1R)-1-[[5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (394 mg, 0.633 mmol), which was used into the next step without further purification (considering a quantitative yield). Step F: Preparation of Example 6 Example 6 was prepared according to a modified General Procedure 3A using N-[2-[4-[(1R)- 1-[[5-(1-acetyl-3,6-dihydro-2H-pyridin-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (394 mg, 0.633 mmol) and trifluoroacetic acid (0.485 mL, 6.33 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase column chromatography (acetonitrile / water / ammonium bicarbonate) to give Example 6 (145 mg, 0.278 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.94 (d, 1H), 8.82 (br d, 1H), 8.76 (d, 1H), 8.22 (t, 1H), 7.82 (d, 1H), 7.67 (d, 1H), 7.5 (m, 2H), 7.42 (s, 1H), 7.36 (m, 2H), 6.34 (br s, 1H), 5.28 (quin, 1H), 4.15 (br s, 2H), 3.72 (s, 2H), 3.68 (m, 2H), 3.4 (br s, 2H), 2.58 (br s, 2H), 2.06 (s, 3H), 1.57 (d, 3H). [M+H]+=523.2317

[0004] Example 7: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinamide   Step A: Preparation of 5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinic acid methyl ester 5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinic acid methyl ester was prepared according to General Procedure 6A using 5-(1,2,3,6-tetrahydropyridin-4-yl)nicotinic acid methyl ester (527 mg, 2.41 mmol) and Intermediate 2 (300 mg, 2.41 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinic acid methyl ester (730 mg, 2.41 mmol). Step B: Preparation of lithium;5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- yl]nicotinate lithium;5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinate was prepared according to General Procedure 4B using 5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin- 4-yl]nicotinic acid methyl ester (730 mg, 2.41 mmol) to give lithium;5-[1-(oxetane-3- carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinate (710 mg, 2.41 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[[5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin- 4-yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6A using Intermediate 1 (450 mg, 1.14 mmol) and lithium;5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinate (336 mg, 1.14 mmol) to give the crude N-[2-[4-[(1R)-1-[[5-[1-(oxetane-3-carbonyl)-3,6- dihydro-2H-pyridin-4-yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (750 mg, 1.13 mmol), which was used into the next step without further purification (considering a quantitative yield). Step D: Preparation of Example 7 Example 7 was prepared according to a modified General Procedure 3A using N-[2-[4-[(1R)- 1-[[5-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinoyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (750 mg, 1.13 mmol) and trifluoroacetic acid (0.864 mL, 11.3 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase column chromatography (acetonitrile / water / ammonium bicarbonate) to give Example 7 (15.0 mg, 0.0266 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.08 (br d, 1H), 8.95 (d, 1H), 8.8 (dd, 1H), 8.25 (d, 1H), 7.85 (d, 1H), 7.72 (d, 1H), 7.5 (d, 2H), 7.45 (s, 1H), 7.39 (d, 2H), 6.38 (m, 1H), 5.27 (quin, 1H), 4.71 (m, 4H), 4.19 (m, 2H), 3.93 (br d, 1H), 3.74 (t, 1H), 3.69 (s, 2H), 3.41 (br t, 1H), 2.56 (br s, 2H), 1.55 (d, 3H). [M+H]+=565.2425 Example 8: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-3- (3,6-dihydro-2H-pyran-4-yl)benzamide   Step A: Preparation of 3-(3,6-dihydro-2H-pyran-4-yl)benzoic acid methyl ester 3-(3,6-dihydro-2H-pyran-4-yl)benzoic acid methyl ester was prepared according to General Procedure 2A using methyl 3-bromobenzoate (500 mg, 2.33 mmol) and 2-(3,6-dihydro-2H- pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (586 mg, 2.79 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 3-(3,6- dihydro-2H-pyran-4-yl)benzoic acid methyl ester (507 mg, 2.32 mmol). Step B: Preparation of lithium;3-(3,6-dihydro-2H-pyran-4-yl)benzoate lithium;3-(3,6-dihydro-2H-pyran-4-yl)benzoate was prepared according to General Procedure 4B using 3-(3,6-dihydro-2H-pyran-4-yl)benzoic acid methyl ester (507 mg, 2.32 mmol) to give lithium;3-(3,6-dihydro-2H-pyran-4-yl)benzoate (488 mg, 2.32 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1- (3,6-dihydro-2H-pyran-4- yl)benzoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[3-(3,6-dihydro-2H-pyran-4-yl)benzoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;3-(3,6- dihydro-2H-pyran-4-yl)benzoate (160 mg, 0.761 mmol) to give the crude N-[2-[4-[(1R)-1- [[3-(3,6-dihydro-2H-pyran-4-yl)benzoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (441 mg, 0.760 mmol), which was used into the next step without further purification (considering a quantitative yield). Step D: Preparation of Example 8 Example 8 was prepared according to a modified General Procedure 3A using N-[2-[4-[(1R)- 1-[[3-(3,6-dihydro-2H-pyran-4-yl)benzoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (441 mg, 0.760 mmol) and trifluoroacetic acid (0.582 mL, 7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase column chromatography (acetonitrile / water / ammonium bicarbonate) to give Example 8 (307 mg, 0.639 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.9 (d, 1H), 7.97 (s, 1H), 7.84 (d, 1H), 7.81 (d, 1H), 7.71 (d, 1H), 7.61 (d, 1H), 7.49 (m, 2H), 7.45 (m, 2H), 7.38 (d, 2H), 6.36 (br s, 1H), 5.26 (quin, 1H), 4.25 (d, 2H), 3.85 (t, 2H), 3.68 (s, 2H), 3.29 (br s, 2H), 1.55 (d, 3H). [M+H]+=481.2105 Example 9: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- morpholino-nicotinamide   Step A: Preparation of 5-morpholinonicotinic acid methyl ester 5-morpholinonicotinic acid methyl ester was prepared according to General Procedure 5 using methyl 5-bromopyridine-3-carboxylate (500 mg, 2.31 mmol) and morpholine (0.243 mL, 2.78 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 5-morpholinonicotinic acid methyl ester (444 mg, 1.80 mmol). Step B: Preparation of lithium;5-morpholinonicotinate lithium;5-morpholinonicotinate was prepared according to General Procedure 4B using 5- morpholinonicotinic acid methyl ester (444 mg, 2.00 mmol) to give lithium;5- morpholinonicotinate (427 mg, 2.00 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[(5-morpholinonicotinoyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(5-morpholinonicotinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;5-morpholinonicotinate (163 mg, 0.761 mmol). The crude residues were engaged into the next step without further purification, considering a quantitative yield. Step D: Preparation of Example 9 Example 9 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(5- morpholinonicotinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (444 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 9 (322 mg, 0.665 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.96 (d, 1H), 8.48 (m, 2H), 7.85 (d, 1H), 7.71 (m, 2H), 7.48 (d, 2H), 7.44 (s, 1H), 7.38 (d, 2H), 5.26 (quin, 1H), 3.77 (m, 4H), 3.68 (s, 2H), 3.24 (m, 4H), 2.03 (m, 2H), 1.54 (d, 3H). [M+H]+=485.2167 Example 10: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-isonicotinamide   Step A: Preparation of 2-morpholinoisonicotinic acid methyl ester 2-morpholinoisonicotinic acid methyl ester was prepared according to General Procedure 5 using methyl 2-bromopyridine-4-carboxylate (1.00 g, 4.63 mmol) and morpholine (484 mg, 5.55 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 2-morpholinoisonicotinic acid methyl ester (471 mg, 1.91 mmol). Step B: Preparation of lithium;2-morpholinoisonicotinate lithium;2-morpholinoisonicotinate was prepared according to General Procedure 4B using 2- morpholinoisonicotinic acid methyl ester (471 mg, 2.12 mmol) to give lithium;2- morpholinoisonicotinate (453 mg, 2.12 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[(2-morpholinoisonicotinoyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(2-morpholinoisonicotinoyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;2- morpholinoisonicotinate (163 mg, 0.761 mmol). The crude residues were engaged into the next step without further purification, considering a quantitative yield. Step D: Preparation of Example 10 Example 10 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(2- morpholinoisonicotinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert- butyl ester (444 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 10 (250 mg, 0.516 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.98 (br d, 1H), 8.24 (d, 1H), 7.85 (d, 1H), 7.71 (br d, 1H), 7.46 (t, 3H), 7.38 (m, 2H), 7.21 (s, 1H), 7.1 (d, 1H), 5.24 (quin, 1H), 3.71 (br d, 4H), 3.68 (s, 2H), 3.5 (br t, 4H), 2.12 (m, 1H), 1.54 (d, 3H). [M+H]+=485.2145 Example 11: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-pyrimidine-4-carboxamide   Step A: Preparation of 2-morpholinopyrimidine-4-carboxylic acid methyl ester 2-morpholinopyrimidine-4-carboxylic acid methyl ester was prepared according to General Procedure 5 using methyl 2-bromopyrimidine-4-carboxylate (500 mg, 2.30 mmol) and morpholine (241 mg, 2.76 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 2-morpholinopyrimidine-4-carboxylic acid methyl ester (346 mg, 1.40 mmol). Step B: Preparation of lithium;2-morpholinopyrimidine-4-carboxylate lithium;2-morpholinopyrimidine-4-carboxylate was prepared according to General Procedure 4B using 2-morpholinopyrimidine-4-carboxylic acid methyl ester (346 mg, 1.55 mmol) to give lithium;2-morpholinopyrimidine-4-carboxylate (333 mg, 1.55 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[(2-morpholinopyrimidine-4- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(2-morpholinopyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;2- morpholinopyrimidine-4-carboxylate (164 mg, 0.761 mmol). The crude residues were engaged into the next step without further purification, considering a quantitative yield. Step D: Preparation of Example 11 Example 11 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(2- morpholinopyrimidine-4-carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (445 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 11 (171 mg, 0.352 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.96 (d, 1H), 8.6 (d, 1H), 7.84 (d, 1H), 7.72 (d, 1H), 7.49 (d, 2H), 7.45 (s, 1H), 7.38 (d, 2H), 7.15 (d, 1H), 5.26 (quin, 1H), 3.83 (br d, 4H), 3.7 (m, 6H), 3.25 (m, 2H), 1.59 (d, 3H). [M+H]+=486.2093 Example 12: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- (3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide   Step A: Preparation of lithium;2- dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate lithium;2-(3,6-dihydro-2H-pyran- pyrimidine-4-carboxylate was prepared according to General Procedure 4B using 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester (or methyl 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate; 507 mg, 2.30 mmol) to give lithium;2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate (488 mg, 2.30 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step B: Preparation of N-[2-[4-[(1R)-1-[[2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;2-(3,6-dihydro-2H- pyran-4-yl)pyrimidine-4-carboxylate (161 mg, 0.761 mmol). The crude residues were engaged into the next step without further purification, considering a quantitative yield. Step C: Preparation of Example 12 Example 12 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[2-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (443 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 12 (236 mg, 0.489 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.17 (d, 1H), 9.02 (d, 1H), 7.83 (m, 2H), 7.71 (d, 1H), 7.53 (m, 3H), 7.44 (s, 1H), 7.39 (d, 2H), 5.31 (quin, 1H), 4.37 (br d, 2H), 3.86 (t, 2H), 3.67 (s, 2H), 2.68 (br s, 2H), 1.92 (m, 2H), 1.62 (d, 3H). [M+H]+=483.1986 -5- Step A: Preparation of 5-[(3S)-tetrahydrofuran-3-yl]oxynicotinic acid methyl ester To a stirred solution of methyl 5-hydroxypyridine-3-carboxylate (500 mg, 3.27 mmol, 1.0 eq.) in tetrahydrofuran (15.0 mL) were added (3R)-tetrahydrofuran-3-ol (288 mg, 3.27 mmol, 1.0 eq.), diisopropylazodicarboxylate (990 mg, 4.90 mmol, 1.5 eq.) and triphenylphosphine (1.29 g, 4.89 mmol, 1.5 eq.) at room temperature and the mixture was stirred until completion of the reaction. Water was added and the aqueous layer was extracted with dichloromethane and the layers were separated. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 5-[(3S)- tetrahydrofuran-3-yl]oxynicotinic acid methyl ester (583 mg, 2.61 mmol). -tetrahydrofuran-3- lithium;5-[(3S)-tetrahydrofuran-3-yl]oxynicotinate was prepared according to General Procedure 4B using 5-[(3S)-tetrahydrofuran-3-yl]oxynicotinic acid methyl ester (583 mg, 2.61 mmol) to give lithium;5-[(3S)-tetrahydrofuran-3-yl]oxynicotinate (547 mg, 2.61 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- -tetrahydrofuran-3-yl]oxynicotinoyl]amino] ethyl]phenyl]-4- acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[(3S)-tetrahydrofuran-3-yl]oxynicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;5-[(3S)- tetrahydrofuran-3-yl]oxynicotinate (164 mg, 0.761 mmol). The crude residues were engaged into the next step without further purification, considering a quantitative yield. Step D: Preparation of Example 13 Example 13 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5- [(3S)-tetrahydrofuran-3-yl]oxynicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (445 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 13 (292 mg, 0.601 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.03 (d, 1H), 8.7 (s, 1H), 8.43 (d, 1H), 7.85 (d, 1H), 7.78 (s, 1H), 7.71 (d, 1H), 7.49 (d, 2H), 7.44 (s, 1H), 7.38 (d, 2H), 5.23 (m, 2H), 3.85 (m, 4H), 3.68 (s, 2H), 2.27 (m, 1H), 2 (m, 2H), 1.99 (m, 1H), 1.97 (m, 1H), 1.54 (d, 3H). [M+H]+=486.2010

[0005] Example 14: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [(3R)-tetrahydrofuran-3-yl]oxy-nicotinamide   Step A: Preparation of 5-[(3R)-tetrahydrofuran-3-yl]oxynicotinic acid methyl ester To a stirred solution of methyl 5-hydroxypyridine-3-carboxylate (500 mg, 3.27 mmol, 1.0 eq.) in tetrahydrofuran (15.0 mL) were added (3S)-tetrahydrofuran-3-ol (288 mg, 3.27 mmol, 1.0 eq.), diisopropylazodicarboxylate (990 mg, 4.90 mmol, 1.5 eq.) and triphenylphosphine (1.29 g, 4.89 mmol, 1.5 eq.) at room temperature and the mixture was stirred until completion of the reaction. Water was added and the aqueous layer was extracted with dichloromethane and the layers were separated. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 5-[(3R)- tetrahydrofuran-3-yl]oxynicotinic acid methyl ester (287 mg, 1.29 mmol). Step B: Preparation of lithium;5-[(3R)-tetrahydrofuran-3-yl]oxynicotinate lithium;5-[(3R)-tetrahydrofuran-3-yl]oxynicotinate was prepared according to General Procedure 4B using 5-[(3R)-tetrahydrofuran-3-yl]oxynicotinic acid methyl ester (287 mg, 1.29 mmol) to give lithium;5-[(3R)-tetrahydrofuran-3-yl]oxynicotinate (276 mg, 1.29 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- -tetrahydrofuran-3-yl]oxynicotinoyl]amino] ethyl]phenyl]-4- acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[(3R)-tetrahydrofuran-3-yl]oxynicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;5-[(3R)- tetrahydrofuran-3-yl]oxynicotinate (164 mg, 0.761 mmol). The crude residues were engaged into the next step without further purification, considering a quantitative yield. D: Preparation of Example 14 Example 14 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5- [(3R)-tetrahydrofuran-3-yl]oxynicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (445 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 14 (267 mg, 0.550 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.03 (d, 1H), 8.7 (s, 1H), 8.43 (d, 1H), 7.85 (d, 1H), 7.78 (s, 1H), 7.71 (d, 1H), 7.49 (d, 2H), 7.44 (s, 1H), 7.38 (d, 2H), 5.23 (m, 2H), 3.85 (m, 4H), 3.68 (s, 2H), 2.27 (m, 1H), 2 (m, 2H), 1.99 (m, 1H), 1.97 (m, 1H), 1.54 (d, 3H). [M+H]+=486.1986 Example 15: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [1-(oxetane-3-carbonyl)-4-piperidyl]nicotinamide   Step A: Preparation of 5-(1-tert-butoxycarbonyl-4-piperidyl)nicotinic acid methyl ester 5-(1-tert-butoxycarbonyl-4-piperidyl)nicotinic acid methyl ester was prepared according to General Procedure 7A using 5-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester (1.00 g, 3.14 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 5-(1-tert-butoxycarbonyl-4-piperidyl)nicotinic acid methyl ester (859 mg, 2.68 mmol). Step B: Preparation of 5-(4-piperidyl)nicotinic acid methyl ester 5-(4-piperidyl)nicotinic acid methyl ester was prepared according to General Procedure 3A using 5-(1-tert-butoxycarbonyl-4-piperidyl)nicotinic acid methyl ester (500 mg, 1.56 mmol) and trifluoroacetic acid (15.6 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 5-(4- piperidyl)nicotinic acid methyl ester (340 mg, 1.54 mmol). Step C: Preparation of 5-[1-(oxetane-3-carbonyl)-4-piperidyl]nicotinic acid methyl ester 5-[1-(oxetane-3-carbonyl)-4-piperidyl]nicotinic acid methyl ester was prepared according to General Procedure 6A using 5-(4-piperidyl)nicotinic acid methyl ester (413mg, 1.87 mmol) and Intermediate 2 (232 mg, 1.87 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[1-(oxetane-3-carbonyl)-4- piperidyl]nicotinic acid methyl ester (570 mg, 1.87 mmol). Step D: Preparation of lithium;5-[1-(oxetane-3-carbonyl)-4-piperidyl]nicotinate lithium;5-[1-(oxetane-3-carbonyl)-4-piperidyl]nicotinate was prepared according to General Procedure 4B using 5-[1-(oxetane-3-carbonyl)-4-piperidyl]nicotinic acid methyl ester (570 mg, 1.87 mmol) to give lithium;5-[1-(oxetane-3-carbonyl)-4-piperidyl]nicotinate (554 mg, 1.87 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step E: Preparation of N-[2- (oxetane-3-carbonyl)-4-piperidyl]nicotinoyl] amino]ethyl]phenyl]-4- carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[1-(oxetane-3-carbonyl)-4-piperidyl]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.760 mmol) and lithium;5-[1-(oxetane-3- carbonyl)-4-piperidyl]nicotinate (225 mg, 0.760 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[5- [1-(oxetane-3-carbonyl)-4-piperidyl]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (507 mg, 0.760 mmol). Step F: Preparation of Example 15 Example 15 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[1- (oxetane-3-carbonyl)-4-piperidyl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (507 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by SFC (carbon dioxide / ethanol / diethylamine) to give Example 15 (177 mg, 0.312 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.01 (m, 1H), 8.92 (s, 1H), 8.63 (s, 1H), 8.12 (s, 1H), 7.85 (d, 1H), 7.71 (d, 1H), 7.49 (d, 2H), 7.44 (s, 1H), 7.38 (d, 2H), 5.27 (m, 1H), 4.72 (m, 4H), 4.58 (br d, 1H), 4.14 (quin, 1H), 3.68 (s, 2H), 3.48 (m, 1H), 3.07 (m, 1H), 2.91 (m, 1H), 2.69 (m, 1H), 2.09 (m, 2H), 1.82 (br t, 2H), 1.56 (m, 5H). [M+H]+=567.2571 Example 16: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(oxetane-3-carbonyl)-4-piperidyl]picolinamide   Step A: Preparation of 4-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)picolinic acid methyl ester 4-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)picolinic acid methyl ester was prepared according to General Procedure 2A using methyl 4-bromopyridine-2-carboxylate (1.00 g, 4.63 mmol) and (1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)boronic acid (1.26 g, 5.55 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 4-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4- yl)picolinic acid methyl ester (1.45 mg, 4.55 mmol). Step B: Preparation of 4-(1-tert-butoxycarbonyl-4-piperidyl)picolinic acid methyl ester 4-(1-tert-butoxycarbonyl-4-piperidyl)picolinic acid methyl ester was prepared according to General Procedure 7B using 4-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)picolinic acid methyl ester (1.00 g, 3.14 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 4-(1-tert-butoxycarbonyl-4-piperidyl)picolinic acid methyl ester (848 mg, 2.65 mmol). Step C: Preparation of 4-(4-piperidyl)picolinic acid methyl ester 4-(4-piperidyl)picolinic acid methyl ester was prepared according to General Procedure 3A using 4-(1-tert-butoxycarbonyl-4-piperidyl)picolinic acid methyl ester (848 mg, 2.65 mmol) and trifluoroacetic acid (26.5 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 4-(4- piperidyl)picolinic acid methyl ester (528 mg, 2.40 mmol). Step D: Preparation of 4-[1-(oxetane-3-carbonyl)-4- picolinic acid methyl ester 4-[1-(oxetane-3-carbonyl)-4-piperidyl]picolinic acid was prepared according to General Procedure 6A using 4-(4-piperidyl)picolinic acid methyl ester (300 mg, 1.36 mmol) and Intermediate 2 (170 mg, 1.36 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[1-(oxetane-3-carbonyl)-4- piperidyl]picolinic acid methyl ester (414 mg, 1.36 mmol). Step E: Preparation of lithium;4-[1-(oxetane-3-carbonyl)-4-piperidyl]picolinate lithium;4-[1-(oxetane-3-carbonyl)-4-piperidyl]picolinate was prepared according to General Procedure 4B using 4-[1-(oxetane-3-carbonyl)-4-piperidyl]picolinic acid methyl ester (414 mg, 1.36 mmol) to give lithium;4-[1-(oxetane-3-carbonyl)-4-piperidyl]picolinate (381 mg, 1.29 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step F: Preparation of N-[2- (oxetane-3-carbonyl)-4-piperidyl]picolinoyl] amino]ethyl]phenyl]-4- carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-[1-(oxetane-3-carbonyl)-4-piperidyl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.760 mmol) and lithium;4-[1-(oxetane-3- carbonyl)-4-piperidyl]picolinate (225 mg, 0.76 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[4- [1-(oxetane-3-carbonyl)-4-piperidyl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (507 mg, 0.760 mmol). Step G: Preparation of Example 16 Example 16 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[1- (oxetane-3-carbonyl)-4-piperidyl]picolinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (507 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give Example 16 (60.0 mg, 0.106 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.08 (d, 1H), 8.58 (d, 1H), 7.92 (s, 1H), 7.83 (s, 1H), 7.7 (m, 1H), 7.51 (m, 3H), 7.43 (m, 1H), 7.36 (d, 2H), 5.24 (quin, 1H), 4.7 (m, 4H), 4.53 (br s, 1H), 4.13 (quin, 1H), 3.67 (s, 2H), 3.46 (br d, 1H), 3.06 (m, 1H), 2.92 (m, 1H), 2.67 (m, 1H), 1.99 (m, 2H), 1.81 (m, 2H), 1.57 (br d, 5H). [M+H]+=567.2577 -5- -4-piperidyl]nicotinic acid methyl ester 5-[1-(cyclopropanecarbonyl)-4-piperidyl]nicotinic acid methyl ester was prepared according to General Procedure 6A using 5-(4-piperidyl)nicotinic acid methyl ester (240 mg, 1.09 mmol) and cyclopropanecarboxylic acid (93.8 mg, 1.09 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[1- (cyclopropanecarbonyl)-4-piperidyl]nicotinic acid methyl ester (314 mg, 1.09 mmol). Step B: Preparation of lithium;5-[1-(cyclopropanecarbonyl)-4-piperidyl]nicotinate lithium;5-[1-(cyclopropanecarbonyl)-4-piperidyl]nicotinate was prepared according to General Procedure 4B using 5-[1-(cyclopropanecarbonyl)-4-piperidyl]nicotinic acid methyl ester (314 mg, 1.09 mmol) to give 5-[1-(cyclopropanecarbonyl)-4-piperidyl]nicotinic acid methyl ester (305 mg, 1.09 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[[5-[1-(cyclopropanecarbonyl)-4-piperidyl] nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[1-(cyclopropanecarbonyl)-4-piperidyl]nicotinoyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.760 mmol) and lithium;5-[1- (cyclopropanecarbonyl)-4-piperidyl]nicotinate (213 mg, 0.760 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2- [4-[(1R)-1-[[5-[1-(cyclopropanecarbonyl)-4-piperidyl]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (495 mg, 0.760 mmol). Step D: Preparation of Example 17 Example 17 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[1- (cyclopropanecarbonyl)-4-piperidyl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl) benzyl]carbamic acid tert-butyl ester (495 mg, 0.761 mmol) and trifluoroacetic acid (7.61 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium hydrogen carbonate) to give Example 17 (282 mg, 0.512 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.92 (d, 1H), 8.76 (m, 1H), 8.61 (m, 1H), 8.09 (m, 1H), 7.84 (s, 1H), 7.66 (m, 1H), 7.49 (d, 2H), 7.41 (m, 1H), 7.37 (s, 1H), 5.27 (quin, 1H), 4.42 (br d, 1H), 3.68 (s, 2H), 3.02 (m, 1H), 2.95 (m, 1H), 1.99 (br s, 1H), 1.89 (br s, 1H), 1.68 (br s, 1H), 1.65 (br s, 1H), 1.56 (s, 2H), 0.72 (m, 4H). [M+H]+=551.2609 Example 18: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- [(3R)-tetrahydrofuran-3-yl]oxy-pyrimidine-4-carboxamide   Step A: Preparation of 2-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-4-carboxylic acid 2-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-4-carboxylic acid (3R)-tetrahydrofuran-3-ol (4.20 g, 47.7 mmol) was added to a suspension of sodium hydride (2.10 g, 52.5 mmol) in tetrahydrofuran (120 mL). The reaction mixture was stirred at room temperature for 30 minutes and a solution of 2-chloropyrimidine-4-carboxylic acid (2.50 g, 15.8 mmol) in tetrahydrofuran (49.0 mL) was added. The reaction mixture was stirred at room temperature for 30 minutes and heated to reflux until completion of the reaction. The mixture was cooled to room temperature and the pH was adjusted to 1 by adding aqueous 1 N hydrogen chloride. The mixture was poured into brine and extracted with dichloromethane to give 2-[(3R)- tetrahydrofuran-3-yl]oxypyrimidine-4-carboxylic acid (3.25 g, 15.5 mmol), which was engaged into the next step without further purification. Step B: Preparation of N-[2- -tetrahydrofuran-3-yl]oxypyrimidine-4- carbonyl]amino]ethyl] - benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[2-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-4-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (250 mg, 0.634 mmol) and 2-[(3R)- tetrahydrofuran-3-yl]oxypyrimidine-4-carboxylic acid (133 mg, 0.634 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[2-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-4-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (371 mg, 0.632 mmol). Step C: Preparation of Example 18 Example 18 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[2- [(3R)-tetrahydrofuran-3-yl]oxypyrimidine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl) benzyl]carbamic acid tert-butyl ester (371 mg, 0.632 mmol) and trifluoroacetic acid (6.32 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium hydrogen carbonate) to give Example 18 (125 mg, 0.257 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.17 (d, 1H), 8.83 (d, 1H), 7.84 (d, 1H), 7.71 (d, 1H), 7.62 (d, 1H), 7.51 (m, 2H), 7.44 (s, 1H), 7.38 (m, 2H), 5.68 (br dd, 1H), 5.25 (quin, 1H), 3.88 (m, 4H), 3.67 (s, 2H), 2.29 (td, 1H), 2.08 (m, 1H), 1.92 (m, 2H), 1.59 (d, 3H). [M+H]+=487.1964 Example 19: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinamide   Step A: Preparation of 5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinic acid methyl ester 5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinic acid methyl ester was prepared according to General Procedure 6A using 5-(1,2,3,6-tetrahydropyridin-4-yl)nicotinic acid methyl ester (342 mg, 1.57 mmol) and cyclopropanecarboxylic acid (135 mg, 1.57 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4- yl]nicotinic acid methyl ester (448 mg, 1.56 mmol). Step B: Preparation of lithium;5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4- yl]nicotinate lithium;5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinate was prepared according to General Procedure 4B using 5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H- pyridin-4-yl]nicotinic acid methyl ester (448 mg, 1.56 mmol) to give lithium;5-[1- (cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinate (435 mg, 1.56 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[[5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H- pyridin-4-yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert- butyl ester N-[2-[4-[(1R)-1-[[5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinoyl] amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;5-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinate (212 mg, 0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[5-[1-(cyclopropanecarbonyl)-3,6- dihydro-2H-pyridin-4-yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (493 mg, 0.760 mmol). Step D: Preparation of Example 19 Example 19 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[1- (cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (493 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium hydrogen carbonate) to give Example 19 (159 mg, 0.290 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.08 (d, 1H), 8.95 (d, 1H), 8.82 (s, 1H), 8.28 (s, 1H), 7.85 (d, 1H), 7.71 (d, 1H), 7.5 (d, 2H), 7.44 (s, 1H), 7.39 (d, 2H), 6.42 (br s, 1H), 5.27 (quin, 1H), 4.28 (m, 2H), 3.83 (m, 2H), 3.68 (s, 2H), 2.64 (m, 2H), 1.98 (br s, 3H), 1.56 (d, 3H), 0.75 (m, 4H). [M+H]+=549.2446 -4- Step A: Preparation of 4-(1,2,3,6-tetrahydropyridin-4-yl)picolinic acid methyl ester 4-(1,2,3,6-tetrahydropyridin-4-yl)picolinic acid methyl ester was prepared according to General Procedure 3A using 5-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)nicotinic acid methyl ester (500 mg, 1.57 mmol) and trifluoroacetic acid (15.7 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 4-(1,2,3,6-tetrahydropyridin-4-yl)picolinic acid methyl ester (315 mg, 1.44 mmol). acid methyl ester 4-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinic acid methyl ester was prepared according to General Procedure 6A using 4-(1,2,3,6-tetrahydropyridin-4-yl)picolinic acid methyl ester (315 mg, 1.44 mmol) and cyclopropanecarboxylic acid (124 mg, 1.44 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4- yl]picolinic acid methyl ester (280 mg, 0.678 mmol). -3,6-dihydro-2H-pyridin-4- lithium;4-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinate was prepared according to General Procedure 4B using 4-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H- pyridin-4-yl]picolinic acid methyl ester (280 mg, 0.978 mmol) to give lithium;4-[1- (cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinate (272 mg, 0.978 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step D: Preparation of N-[2- (cyclopropanecarbonyl)-3,6-dihydro-2H- pyridin-4-yl]picolinoyl] - (trifluoromethyl)benzyl]carbamic acid tert- butyl ester N-[2-[4-[(1R)-1-[[4-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl] amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;4-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinate (212 mg, 0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[4-[1-(cyclopropanecarbonyl)-3,6- dihydro-2H-pyridin-4-yl]picolinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (493 mg, 0.760 mmol). Step E: Preparation of Example 20 Example 20 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[1- (cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (494 mg, 0.762 mmol) and trifluoroacetic acid (7.62 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give Example 20 (97.0 mg, 0.177 mmol). 1H NMR (400 MHz, dmso-d6) δ ppm 8.79 (br d, 1H), 8.6 (d, 1H), 8.05 (d, 1H), 7.81 (d, 1H), 7.66 (d, 1H), 7.62 (dd, 1H), 7.51 (d, 2H), 7.41 (d, 1H), 7.35 (d, 2H), 6.56 (t, 1H), 5.26 (quin, 1H), 4.29 (br s, 2H), 3.81 (br s, 2H), 3.69 (s, 2H), 2.56 (br s, 2H), 1.97 (m, 1H), 1.65 (br s, 2H), 1.6 (d, 3H), 0.75 (m, 4H). [M+H]+=549.2470 Example 21: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [4-(cyclopropanecarbonyl)piperazino]nicotinamide   Step A: Preparation of 5-[4-(cyclopropanecarbonyl)piperazino]nicotinic acid methyl ester 5-[4-(cyclopropanecarbonyl)piperazino]nicotinic acid methyl ester was prepared according to General Procedure 6A using Intermediate 3 (205 mg, 0.927 mmol) and cyclopropanecarboxylic acid (79.8 mg, 0.927 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[4- (cyclopropanecarbonyl)piperazino]nicotinic acid methyl ester (268 mg, 0.926 mmol). Step B: Preparation of lithium;5-[4-(cyclopropanecarbonyl)piperazino]nicotinate lithium;5-[4-(cyclopropanecarbonyl)piperazino]nicotinate was prepared according to General Procedure 4B using 5-[4-(cyclopropanecarbonyl)piperazino]nicotinic acid methyl ester (268 mg, 0.926 mmol) to give lithium;5-[4-(cyclopropanecarbonyl)piperazino]nicotinate (260 mg, 0.925 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- (cyclopropanecarbonyl)piperazino]nicotinoyl] amino]ethyl]phenyl]-4- carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[4-(cyclopropanecarbonyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (350 mg, 0.887 mmol) and lithium;5-[4- (cyclopropanecarbonyl)piperazino]nicotinate (250 mg, 0.887 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4- [(1R)-1-[[5-[4-(cyclopropanecarbonyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (578 mg, 0.887 mmol). Step D: Preparation of Example 21 Example 21 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[4- (cyclopropanecarbonyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (578 mg, 0.887 mmol) and trifluoroacetic acid (8.87 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 21 (331 mg, 0.600 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.97 (d, 1H), 8.52 (d, 1H), 8.46 (d, 1H), 7.85 (d, 1H), 7.72 (m, 2H), 7.49 (d, 2H), 7.44 (s, 1H), 7.38 (d, 2H), 5.26 (m, 1H), 3.86 (m, 2H), 3.68 (s, 2H), 3.63 (m, 2H), 3.25 (m, 4H), 2.2 (m, 2H), 2.03 (m, 1H), 1.55 (d, 3H), 0.75 (m, 4H). [M+H]+=552.2581 Example 22: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinamide Step A: Preparation of 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinic acid methyl ester To a stirred solution of 4-(1,2,3,6-tetrahydropyridin-4-yl)picolinic acid methyl ester (294 mg, 1.35 mmol) in tetrahydrofuran (10.0 mL) was added oxetan-3-one (146 mg, 2.02 mmol) and acetic acid (0.154 ml, 2.69 mmol). The reaction mixture was stirred one hour at room temperature and the reaction was cooled to 0 °C. Sodium triacetoxyborohydride (857 mg, 4.04 mmol) was then added in one portion and the reaction mixture was allowed to warm to room temperature and was stirred until completion of the reaction. The solvent was removed under reduced pressure and the residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinic acid methyl ester (237 mg, 0.864 mmol). Step B: Preparation of lithium;4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinate lithium;4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinate was prepared according to General Procedure 4B using 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinic acid methyl ester (237 mg, 0.864mmol) to give lithium;4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin- 4-yl]picolinate (230 mg, 0.864 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1- [1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4- yl]picolinoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl]amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;4-[1-(oxetan- 3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinate (203 mg,0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4- [(1R)-1-[[4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (484 mg, 0.761 mmol). Step D: Preparation of Example 22 Example 22 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[1- (oxetan-3-yl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (484 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 22 (182 mg, 0.339 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.77 (br d, 1H), 8.58 (m, 1H), 8.03 (d, 1H), 7.81 (d, 1H), 7.66 (d, 1H), 7.59 (dd, 1H), 7.5 (d, 2H), 7.41 (d, 1H), 7.35 (d, 2H), 6.53 (m, 1H), 5.25 (m, 1H), 4.55 (m, 4H), 3.69 (s, 2H), 3.63 (m, 1H), 3.1 (m, 2H), 2.59 (m, 2H), 2.52 (m, 2H), 1.63 (br s, 2H), 1.6 (m, 3H). [M+H]+=537.2457 -4- Step A: Preparation of methyl 4-[1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carboxylate To a stirred solution of methyl 4-(4-piperidyl)pyridine-2-carboxylate (or 4-(4- piperidyl)picolinic acid methyl ester; 334 mg, 1.52 mmol) in tetrahydrofuran (10.0 mL) was added oxetan-3-one (164 mg, 2.27 mmol) and acetic acid (0.174 ml, 3.03 mmol). The reaction mixture was stirred one hour at room temperature and the reaction was cooled to 0 °C. Sodium triacetoxyborohydride (964 mg, 4.55 mmol) was then added in one portion and the reaction mixture was allowed to warm to room temperature and was stirred until completion of the reaction. The solvent was removed under reduced pressure and the residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 4- [1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carboxylate (323 mg, 1.17 mmol). Step B: Preparation of lithium;4-[1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carboxylate Lithium;4-[1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carboxylate was prepared according to General Procedure 4B using methyl 4-[1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carboxylate (323 mg, 1.17 mmol) to give lithium;4-[1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carboxylate (313 mg, 1.17 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. (oxetan-3-yl)-4- tert-butyl N-[[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (350 mg, 0.887 mmol) and lithium;4-[1-(oxetan-3-yl)-4- piperidyl]pyridine-2-carboxylate (238 mg, 0.887 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[[2-[4-[(1R)-1-[[4- [1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (566 mg, 0.886 mmol). Step D: Preparation of Example 23 Example 23 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-[1-(oxetan-3-yl)-4-piperidyl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl) phenyl]methyl]carbamate (566 mg, 0.886 mmol) and trifluoroacetic acid (8.66 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 23 (216 mg, 0.401 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.08 (d, 1H), 8.58 (m, 1H), 7.91 (s, 1H), 7.84 (d, 1H), 7.71 (d, 1H), 7.53 (m, 3H), 7.44 (s, 1H), 7.36 (d, 2H), 5.25 (m, 1H), 4.49 (m, 4H), 3.67 (s, 2H), 3.42 (m, 1H), 2.81 (m, 2H), 2.66 (m, 1H), 2.06 (m, 2H), 1.89 (m, 2H), 1.81 (m, 2H), 1.68 (m, 2H), 1.58 (d, 3H). [M+H]+=539.2614 Example 24: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(cyclopropanecarbonyl)-4-piperidyl]picolinamide   Step A: Preparation of 4-[1-(cyclopropanecarbonyl)-4-piperidyl]picolinic acid methyl ester 4-[1-(cyclopropanecarbonyl)-4-piperidyl]picolinic acid methyl ester was prepared according to General Procedure 6A using 4-(4-piperidyl)picolinic acid methyl ester (228 mg, 1.04 mmol) and cyclopropanecarboxylic acid (89.1 mg, 1.04 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[1- (cyclopropanecarbonyl)-4-piperidyl]picolinic acid methyl ester (285 mg, 0.989 mmol). Step B: Preparation of lithium;4-[1-(cyclopropanecarbonyl)-4-piperidyl]picolinate lithium;4-[1-(cyclopropanecarbonyl)-4-piperidyl]picolinate was prepared according to General Procedure 4B using 4-[1-(cyclopropanecarbonyl)-4-piperidyl]picolinic acid methyl ester (285 mg, 0.989 mmol) to give lithium;4-[1-(cyclopropanecarbonyl)-4- piperidyl]picolinate (277 mg, 0.989 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- (cyclopropanecarbonyl)-4-piperidyl] picolinoyl]amino]ethyl] - benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-[1-(cyclopropanecarbonyl)-4-piperidyl]picolinoyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;4-[1- (cyclopropanecarbonyl)-4-piperidyl]picolinate (213 mg, 0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2- [4-[(1R)-1-[[4-[1-(cyclopropanecarbonyl)-4-piperidyl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (495 mg, 0.761 mmol). Step D: Preparation of Example 24 Example 24 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[1- (cyclopropanecarbonyl)-4-piperidyl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (495 mg, 0.761 mmol) and trifluoroacetic acid (7.61 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by SFC (carbon dioxide / ethanol / diethylamine) to give Example 24 (137 mg, 0.249 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.76 (br d, 1H), 8.55 (d, 1H), 7.93 (s, 1H), 7.81 (d, 1H), 7.66 (br d, 1H), 7.49 (m, 3H), 7.41 (s, 1H), 7.34 (d, 2H), 5.25 (quin, 1H), 4.44 (br d, 2H), 3.69 (s, 2H), 2.94 (m, 3H), 1.92 (m, 3H), 1.59 (d, 3H), 1.58 (m, 4H), 0.73 (m, 4H). [M+H]+=551.2618 Example 25: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [4-(cyclopropanecarbonyl)piperazino]picolinamide   Step A: Preparation of 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid methyl ester 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid methyl ester was prepared according to General Procedure 6A using 4-piperazinopicolinic acid methyl ester (298 mg, 1.35 mmol) and cyclopropanecarboxylic acid (116 mg, 1.35 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[4- (cyclopropanecarbonyl)piperazino]picolinic acid methyl ester (389 mg, 1.35 mmol). Step B: Preparation of lithium;4-[4-(cyclopropanecarbonyl)piperazino]picolinate lithium;4-[4-(cyclopropanecarbonyl)piperazino]picolinate was prepared according to General Procedure 4B using 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid methyl ester (389 mg, 1.35 mmol) to give lithium;4-[4-(cyclopropanecarbonyl)piperazino]picolinate (378 mg, 1.35 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1- [4-(cyclopropanecarbonyl)piperazino]picolinoyl] amino]ethyl]phenyl]-4-(trifluoromethyl) carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-[4-(cyclopropanecarbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (400 mg, 1.01 mmol) and lithium;4-[4- (cyclopropanecarbonyl)piperazino]picolinate (285 mg, 1.01 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4- [(1R)-1-[[4-[4-(cyclopropanecarbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (661 mg, 1.01 mmol). Step D: Preparation of Example 25 Example 25 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[4- (cyclopropanecarbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (661 mg, 1.01 mmol) and trifluoroacetic acid (10.1 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 25 (232 mg, 0.421 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.68 (br d, 1H), 8.23 (d, 1H), 7.81 (d, 1H), 7.66 (d, 1H), 7.47 (m, 3H), 7.41 (s, 1H), 7.34 (d, 2H), 6.95 (dd, 1H), 5.22 (quin, 1H), 3.72 (m, 4H), 3.69 (s, 2H), 3.46 (br t, 4H), 1.94 (m, 1H), 1.62 (br s, 2H), 1.58 (d, 3H), 0.75 (m, 4H). [M+H]+=552.2572 -4- of 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinic acid methyl ester 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinic acid methyl ester was prepared according to General Procedure 6A using 4-(1,2,3,6-tetrahydropyridin-4-yl)picolinic acid methyl ester (294 mg, 1.35 mmol, 1.0 eq.) and Intermediate 2 (167 mg, 1.35 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- yl]picolinic acid methyl ester (407 mg, 1.35 mmol). of 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinate was prepared according to General Procedure 4B using 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinic acid methyl ester (407 mg, 1.35 mmol) to give 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H- pyridin-4-yl]picolinate (396 mg, 1.35 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1- [1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin- 4-yl]picolinoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl]amino] ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (400 mg, 1.01 mmol) and 4-[1-(oxetane-3- carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinate (298 mg, 1.01 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2- [4-[(1R)-1-[[4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl]amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (242 mg, 0.364 mmol). Step D: Preparation of Example 26 Example 26 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[1- (oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (242 mg, 0.364 mmol) and trifluoroacetic acid (3.64 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (carbon dioxide / methanol / diethylamine) to give Example 26 (51.0 mg, 0.0903 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.12 (br d, 1H), 8.63 (d, 1H), 8.02 (br s, 1H), 7.84 (d, 1H), 7.71 (br d, 1H), 7.66 (m, 1H), 7.52 (br d, 2H), 7.44 (s, 1H), 7.37 (d, 2H), 6.58 (m, 1H), 5.25 (m, 1H), 4.71 (m, 4H), 4.14 (m, 3H), 3.67 (s, 2H), 3.52 (m, 2H), 2.58 (m, 2H), 2.11 (m, 1H), 1.58 (d, 3H). [M+H]+=565.2398

[0006] Example 27: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [4-(oxetan-3-ylmethyl)piperazino]nicotinamide   Step A: Preparation of 5-[4-(oxetan-3-ylmethyl)piperazino]nicotinic acid methyl ester To a stirred solution of Intermediate 3 (224 mg, 1.01 mmol) in acetonitrile (5.00 mL) were added potassium carbonate (126 mg, 0.911 mmol) and 3-(bromomethyl)oxetane (168 mg, 1.11 mmol) and the mixture was heated to 80 °C. After completion of the reaction, water was added and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[4-(oxetan-3-ylmethyl)piperazino]nicotinic acid methyl ester (172 mg, 0.591 mmol). Step B: Preparation of lithium;5-[4-(oxetan-3-ylmethyl)piperazino]nicotinate lithium;5-[4-(oxetan-3-ylmethyl)piperazino]nicotinate was prepared according to General Procedure 4B using 5-[4-(oxetan-3-ylmethyl)piperazino]nicotinic acid methyl ester (172 mg, 0.591 mmol) to give lithium;5-[4-(oxetan-3-ylmethyl)piperazino]nicotinate (167 mg, 0.591 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- (oxetan-3-ylmethyl)piperazino]nicotinoyl] amino]ethyl]phenyl]-4- carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[4-(oxetan-3-ylmethyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (230 mg, 0.583 mmol) and lithium;5-[4-(oxetan-3- ylmethyl)piperazino]nicotinate (165 mg, 0.583 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[5- [4-(oxetan-3-ylmethyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (381 mg, 0.583 mmol). Step D: Preparation of Example 27 Example 27 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[4- (oxetan-3-ylmethyl)piperazino]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (381 mg, 0.583 mmol) and trifluoroacetic acid (5.83 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (carbon dioxide / methanol / diethylamine) to give Example 27 (101 mg, 0.182 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.94 (d, 1H), 8.48 (d, 1H), 8.41 (d, 1H), 7.85 (d, 1H), 7.71 (dd, 1H), 7.68 (m, 1H), 7.48 (d, 2H), 7.44 (d, 1H), 7.38 (d, 2H), 5.25 (quin, 1H), 4.66 (dd, 2H), 4.28 (t, 2H), 3.68 (s, 2H), 3.23 (m, 5H), 2.68 (d, 2H), 2.49 (br s, 4H), 2 (m, 2H), 1.54 (d, 3H). [M+H]+=554.2710 Example 28: N-[(1R)-1-[4-[2-(aminomethyl)-5-chloro-phenyl]phenyl]ethyl]-4-[4- (cyclopropanecarbonyl)piperazino]picolinamide   Step A: Preparation of (2-bromo-4-chloro-benzyl)amine To a solution of 2-bromo-4-chloro-benzonitrile (5.00 g, 23.1 mmol, 1.0 eq.) in tetrahydrofuran (30.0 mL) was slowly added a 1 M borane tetrahydrofuran complex solution (46.2 mL, 46.2 mmol, 2.0 eq.) at 0 °C and the mixture was heated to reflux. After completion of the reaction, the mixture was quenched with a 2 M aqueous solution of hydrogen chloride (45.0 mL, 90.0 mmol, 3.9 eq.). The aqueous layer was extracted with dichloromethane and the pH was adjusted to pH=8 with an aqueous 2 M solution of sodium hydroxide. The aqueous layer was extracted with dichloromethane and the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give (2-bromo- 4-chloro-benzyl)amine (3.70 g, 17.0 mmol), which was used into the next step without further purification.1H NMR (400 MHz, dmso-d6) δ ppm 7.68 (d, 1H), 7.58 (d, 1H), 7.46 (dd, 1H), 3.72 (s, 2H), 3.38 (m, 1H), 1.92 (br s, 2H). Step B: Preparation of N-(2-bromo-4-chloro-benzyl)carbamic acid tert-butyl ester To a stirred solution of (2-bromo-4-chloro-benzyl)amine (3.70 g, 17.0 mmol, 1.0 eq.) and triethylamine (4.20 g, 42.0 mmol, 2.5 eq.) in dichloromethane (60.0 mL), was added di-tert- butyl dicarbonate (4.80 g, 22.0 mmol, 1.3 eq.). After completion of the reaction, the mixture was partitioned between water and dichloromethane. The aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (n-heptane / ethyl acetate) to give N-(2-bromo-4-chloro- benzyl)carbamic acid tert-butyl ester (4.70 g, 15.0 mmol). Step C: Preparation of N-[4-chloro-2-[4-[(1R)-1-phthalimidoethyl]phenyl]benzyl]carbamic acid tert-butyl ester N-[4-chloro-2-[4-[(1R)-1-phthalimidoethyl]phenyl]benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 2B using N-(2-bromo-4-chloro-benzyl)carbamic acid tert-butyl ester (4.70 g, 15.0 mmol, 1.0 eq.) and 2-[(1R)-1-[4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)phenyl]ethyl]isoindoline-1,3-quinone (6.60 g,18.0 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (n-heptane / ethyl acetate) to give N-[4-chloro-2-[4-[(1R)-1-phthalimidoethyl]phenyl]benzyl]carbamic acid tert-butyl ester (6.60 g, 13.0 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 7.87 (m, 4H), 7.45 (m, 3H), 7.36 (m, 4H), 7.21 (d, 1H), 5.53 (q, 1H), 4 (d, 2H), 1.88 (d, 3H), 1.35 (s, 7H). Step D: Preparation of N-[2-[4-[(1R)-1-aminoethyl]phenyl]-4-chloro-benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-aminoethyl]phenyl]-4-chloro-benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 1 using N-[4-chloro-2-[4-[(1R)-1-phthalimidoethyl] phenyl]benzyl]carbamic acid tert-butyl ester (6.60 g, 13.0 mmol, 1.0 eq.) and hydrazine (5.6 mL, 67.0 mmol, 5.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol-methanol) to give N-[2-[4-[(1R)-1- aminoethyl]phenyl]-4-chloro-benzyl]carbamic acid tert-butyl ester (4.24 g, 11.7 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 7.46 (s, 2H), 7.39 (m, 3H), 7.29 (br d, 2H), 7.21 (d, 1H), 4.03 (d, 3H), 1.88 (br s, 2H), 1.37 (s, 9H), 1.28 (d, 3H). Step E: Preparation of 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid was prepared according to General Procedure 4A using 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid methyl ester (320 mg, 1.11 mmol) to give 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid (600 mg, 2.18 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification.1H NMR (400 MHz, dmso-d6) δ ppm 8.11 (d, 1H), 7.47 (d, 1H), 7.16 (dd, 1H), 3.89 (br s, 2H), 3.8 (br s, 2H), 3.71 (br s, 2H), 3.66 (br s, 2H), 1.99 (m, 1H), 0.76 (m, 4H). Step F: Preparation of N-[4-chloro-2-[4-[(1R)-1- [4-(cyclopropanecarbonyl)piperazino] picolinoyl]amino]ethyl]phenyl]benzyl]carbamic tert-butyl ester N-[4-chloro-2-[4-[(1R)-1-[[4-[4-(cyclopropanecarbonyl)piperazino]picolinoyl]amino]ethyl] phenyl]benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using N-[2-[4-[(1R)-1-aminoethyl]phenyl]-4-chloro-benzyl]carbamic acid tert-butyl ester (197 mg, 0.545 mmol, 1.0 eq.) and 4-[4-(cyclopropanecarbonyl)piperazino]picolinic acid (150 mg, 0.545 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to give N-[4-chloro-2-[4-[(1R)-1-[[4-[4- (cyclopropanecarbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]benzyl]carbamic acid tert- butyl ester (110 mg, 0.327 mmol). Step G: Preparation of Example 28 Example 28 was prepared according to a modified General Procedure 3A using N-[4-chloro- 2-[4-[(1R)-1-[[4-[4-(cyclopropanecarbonyl)piperazino]picolinoyl]amino]ethyl]phenyl]benzyl] carbamic acid tert-butyl ester (110 mg, 0.178 mmol, 1.0 eq.) and trifluoroacetic acid (1.78 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 28 (70.0 mg, 0.135 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.94 (d, 1H), 8.26 (d, 1H), 7.6 (d, 1H), 7.48 (d, 2H), 7.45 (d, 1H), 7.41 (m, 1H), 7.34 (d, 2H), 7.2 (d, 1H), 7.01 (dd, 1H), 5.21 (m, 1H), 3.83 (br s, 2H), 3.59 (s, 4H), 3.5 (br s, 2H), 3.42 (m, 2H), 2.34 (m, 2H), 2 (m, 1H), 1.56 (d, 3H), 0.75 (m, 4H). [M+H]+=518.2323 Example 29: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide Step A: Preparation of 2-chloro-6-cyclopropyl-pyrimidine-4-carboxylic acid methyl ester 2-chloro-6-cyclopropyl-pyrimidine-4-carboxylic acid methyl ester was prepared according to General Procedure 2A using methyl 2,6-dichloropyrimidine-4-carboxylate (1.00 g, 4.83 mmol) and cyclopropylboronic acid (0.415 g, 4.83 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (n-heptane / ethyl acetate) to give 2-chloro-6- cyclopropyl-pyrimidine-4-carboxylic acid methyl ester (0.344 g, 1.62 mmol).1H NMR (500 MHz, dmso-d6) δ ppm 8.03 (s, 1H), 3.91 (s, 3H), 2.37 (tt, 1H), 1.22 (m, 2H), 1.12 (m, 2H). Step B: Preparation of 6-cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester 6-cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester was prepared according to General Procedure 2A using 2-chloro-6-cyclopropyl-pyrimidine-4- carboxylic acid methyl ester (0.344 g, 1.62 mmol) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane (0.408 g, 1.94 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (n-heptane / ethyl acetate) to give 6-cyclopropyl- 2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester (0.307 g, 1.18 mmol). Step C: Preparation of lithium;6-cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4- carboxylate lithium;6-cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate was prepared according to General Procedure 4B using 6-cyclopropyl-2-(3,6-dihydro-2H-pyran-4- yl)pyrimidine-4-carboxylic acid methyl ester (307 mg, 1.18 mmol, 1.0 eq.) to give lithium;6- cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate (297 mg, 1.18 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step D: Preparation of N-[2-[4-[(1R)-1- cyclopropyl-2-(3,6-dihydro-2H-pyran-4- yl)pyrimidine-4-carbonyl]amino]ethyl] -4-(trifluoromethyl)benzyl]carbamic acid tert- butyl ester N-[2-[4-[(1R)-1-[[6-cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl] amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol, 1.0 eq.) and lithium;6-cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate (192 mg, 0.761 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[6-cyclopropyl-2-(3,6-dihydro-2H- pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (473 mg, 0.760 mmol). Step E: Preparation of Example 29 Example 29 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[6- cyclopropyl-2-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (473 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 29 (254 mg, 0.486 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (d, 1H), 7.84 (d, 1H), 7.75 (s, 1H), 7.71 (dd, 1H), 7.51 (d, 2H), 7.41 (m, 4H), 5.29 (m, 1H), 4.34 (br d, 2H), 3.83 (t, 2H), 3.67 (s, 2H), 2.62 (br s, 2H), 2.28 (quin, 1H), 1.83 (br d, 2H), 1.61 (d, 3H), 1.11 (m, 4H). [M+H]+=523.2315 Example 30: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- (3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide   Step A: Preparation of 6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester 6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester was prepared according to General Procedure 2A using methyl 6-chloropyrimidine-4-carboxylate (1.00 g, 5.79 mmol, 1.0 eq.) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (1.46 g, 6.95 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (n-heptane / ethyl acetate) to give 6-(3,6-dihydro-2H-pyran-4- yl)pyrimidine-4-carboxylic acid methyl ester (0.760 g, 3.45 mmol). Step B: Preparation of lithium;6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate lithium;6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylate was prepared according to General Procedure 4B using 6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester (250 mg, 1.14 mmol, 1.0 eq.) to give lithium;6-(3,6-dihydro-2H-pyran-4- yl)pyrimidine-4-carboxylate (240 mg, 1.13 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1- (3,6-dihydro-2H-pyran-4-yl)pyrimidine-4- carbonyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol, 1.0 eq.) and lithium;6-(3,6-dihydro- 2H-pyran-4-yl)pyrimidine-4-carboxylate (161 mg, 0.761 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2- [4-[(1R)-1-[[6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (443 mg, 0.760 mmol). Step D: Preparation of Example 30 Example 30 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[6-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl) benzyl]carbamic acid tert-butyl ester (443 mg, 7.60 mmol) and trifluoroacetic acid (0.760 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 30 (232 mg, 0.481 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.38 (d, 1H), 9.27 (d, 1H), 8.05 (d, 1H), 7.83 (s, 1H), 7.71 (dd, 1H), 7.52 (d, 2H), 7.4 (m, 3H), 7.23 (br s, 1H), 5.26 (m, 1H), 4.33 (q, 2H), 3.84 (t, 2H), 3.67 (s, 2H), 2.56 (br d, 2H), 1.86 (br s, 2H), 1.59 (d, 3H). [M+H]+=483.2014 -6- Step A: Preparation of 6-tetrahydropyran-4-ylpyrimidine-4-carboxylic acid methyl ester 6-tetrahydropyran-4-ylpyrimidine-4-carboxylic acid methyl ester was prepared according to a modified General Procedure 7A using 6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester (500 mg, 2.27 mmol) to give the crude 6-tetrahydropyran-4-ylpyrimidine-4- carboxylic acid methyl ester (453 mg, 2.04 mmol) which was used into the next step without further purification. Step B: Preparation of lithium;6-tetrahydropyran-4-ylpyrimidine-4-carboxylate lithium;6-tetrahydropyran-4-ylpyrimidine-4-carboxylate was prepared according to General Procedure 4B using 6-tetrahydropyran-4-ylpyrimidine-4-carboxylic acid methyl ester (453 mg, 2.04 mmol) to give lithium;6-tetrahydropyran-4-ylpyrimidine-4-carboxylate (436 mg, 2.03 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[ -1-[(6-tetrahydropyran-4-ylpyrimidine-4- carbonyl)amino]ethyl]phenyl]- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(6-tetrahydropyran-4-ylpyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.760 mmol) and lithium;6-tetrahydropyran-4- ylpyrimidine-4-carboxylate (163 mg, 0.760 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[(6- tetrahydropyran-4-ylpyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (444 mg, 0.759 mmol). Step D: Preparation of Example 31 Example 31 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(6- tetrahydropyran-4-ylpyrimidine-4-carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl) benzyl]carbamic acid tert-butyl ester (444 mg, 0.759 mmol) and trifluoroacetic acid (7.59 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 31 (278 mg, 0.574 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.37 (d, 1H), 9.27 (d, 1H), 7.92 (d, 1H), 7.84 (d, 1H), 7.71 (dd, 1H), 7.52 (m, 2H), 7.44 (s, 1H), 7.37 (m, 2H), 5.26 (quin, 1H), 3.96 (br dd, 2H), 3.67 (s, 2H), 3.46 (td, 2H), 3.09 (m, 1H), 1.9 (m, 1H), 1.79 (m, 5H), 1.58 (d, 3H). [M+H]+=485.2168

[0007] Example 32: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- (3,6-dihydro-2H-pyran-4-yl)pyrazinamide   Step A: Preparation of 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinic acid methyl ester 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinic acid methyl ester was prepared according to General Procedure 2A using methyl 6-bromopyrazine-2-carboxylate (1.00 g, 4.61 mmol) and 2-(3,6- dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.16 g, 5.53 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinic acid methyl ester (1.01 g, 4.59 mmol). Step B: Preparation of 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinate;lithium(1-) 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinate;lithium(1-) was prepared according to General Procedure 4B using 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinic acid methyl ester (500 mg, 2.27 mmol) to give 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinate;lithium(1-) (480 mg, 2.26 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1- (3,6-dihydro-2H-pyran-4- yl)pyrazinoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[6-(3,6-dihydro-2H-pyran-4-yl)pyrazinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.760 mmol) and 6-(3,6-dihydro-2H-pyran-4- yl)pyrazinate;lithium(1-) (161 mg, 0.760 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[6-(3,6- dihydro-2H-pyran-4-yl)pyrazinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (443 mg, 0.760 mmol). Step D: Preparation of Example 32 Example 32 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[6-(3,6- dihydro-2H-pyran-4-yl)pyrazinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (443 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 32 (232 mg, 0.481 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (d, 1H), 9.03 (d, 2H), 7.84 (d, 1H), 7.72 (br d, 1H), 7.52 (d, 2H), 7.44 (m, 1H), 7.38 (d, 2H), 7.2 (m, 1H), 5.32 (m, 1H), 4.35 (q, 2H), 3.88 (t, 2H), 3.67 (s, 2H), 2.7 (br d, 2H), 1.93 (m, 2H), 1.62 (d, 3H). [M+H]+=483.2006 Example 33: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- tetrahydropyran-4-yl-pyrazinamide   Step A: Preparation of 6-tetrahydropyran-4-ylpyrazinic acid methyl ester 6-tetrahydropyran-4-ylpyrazinic acid methyl ester was prepared according to a modified General Procedure 7A using 6-(3,6-dihydro-2H-pyran-4-yl)pyrazinic acid methyl ester (890 mg, 4.04 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 6-tetrahydropyran-4-ylpyrazinic acid methyl ester (466 mg, 2.09 mmol). Step B: Preparation of lithium;6-tetrahydropyran-4-ylpyrazinate lithium;6-tetrahydropyran-4-ylpyrazinate was prepared according to General Procedure 4B using 6-tetrahydropyran-4-ylpyrazinic acid methyl ester (466 mg, 2.09 mmol) to give lithium;6-tetrahydropyran-4-ylpyrazinate (449 mg, 2.09 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[(6-tetrahydropyran-4- ylpyrazinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(6-tetrahydropyran-4-ylpyrazinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl) benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.760 mmol) and lithium;6-tetrahydropyran-4-ylpyrazinate (163 mg, 0.760 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[(6-tetrahydropyran-4-ylpyrazinoyl) amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (444 mg, 0.759 mmol). Step D: Preparation of Example 33 Example 33 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(6- tetrahydropyran-4-ylpyrazinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (444 mg, 0.759 mmol) and trifluoroacetic acid (7.59 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 33 (340 mg, 0.702 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (d, 1H), 9.02 (s, 1H), 8.83 (s, 1H), 7.84 (d, 1H), 7.71 (dd, 1H), 7.53 (d, 2H), 7.44 (d, 1H), 7.39 (d, 2H), 5.31 (quin, 1H), 4 (dd, 2H), 3.68 (s, 2H), 3.49 (td, 2H), 3.15 (tt, 1H), 1.92 (m, 6H), 1.62 (d, 3H). [M+H]+=485.2167 Example 34: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [4-[[(2R)-oxetan-2-yl]methyl]piperazino]nicotinamide   Step A: Preparation of 5-[4-[[(2R)-oxetan-2-yl]methyl]piperazino]nicotinic acid methyl ester To a stirred solution of Intermediate 3 (300 mg, 0.614 mmol) in acetonitrile (0.3 M) were added potassium carbonate (168 mg, 1.22 mmol) and (2R)-2-(bromomethyl)oxetane (225 mg, 1.49 mmol) and the mixture was heated to 80 °C until completion of the reaction. Water was added and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[4-[[(2R)-oxetan-2- yl]methyl]piperazino]nicotinic acid methyl ester (179 mg, 0.614 mmol). Step B: Preparation of lithium;5-[4-[[(2R)-oxetan-2-yl]methyl]piperazino]nicotinate Lithium;5-[4-[[(2R)-oxetan-2-yl]methyl]piperazino]nicotinate was prepared according to General Procedure 4B using 5-[4-[[(2R)-oxetan-2-yl]methyl]piperazino]nicotinic acid methyl ester (179 mg, 0.614 mmol) to give lithium;5-[4-[[(2R)-oxetan-2-yl]methyl]piperazino] nicotinate (174 mg, 0.614 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- -oxetan-2-yl]methyl]piperazino] nicotinoyl]amino]ethyl] - carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[4-[[(2R)-oxetan-2-yl]methyl]piperazino]nicotinoyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (240 mg, 0.608 mmol) and lithium;5-[4-[[(2R)-oxetan-2- yl]methyl]piperazino]nicotinate (172 mg, 0.608 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[5- [4-[[(2R)-oxetan-2-yl]methyl]piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (397 mg, 0.607 mmol). Step D: Preparation of Example 34 Example 34 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[4- [[(2R)-oxetan-2-yl]methyl]piperazino]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl) benzyl]carbamic acid tert-butyl ester (397 mg, 0.607 mmol) and trifluoroacetic acid (6.07 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 34 (198 mg, 0.357 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.95 (d, 1H), 8.48 (d, 1H), 8.41 (d, 1H), 7.85 (d, 1H), 7.7 (m, 2H), 7.48 (m, 2H), 7.44 (d, 1H), 7.38 (d, 2H), 5.25 (quin, 1H), 4.93 (qd, 1H), 4.51 (td, 1H), 4.39 (dt, 1H), 3.68 (s, 2H), 3.25 (m, 4H), 2.69 (m, 1H), 2.59 (m, 6H), 2.38 (ddt, 1H), 1.99 (m, 2H), 1.54 (d, 3H). [M+H]+=554.2734 -2- Step A: Preparation of 2-chloro-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester 2-chloro-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid methyl ester was prepared according to General Procedure 2A using methyl 2,6-dichloropyrimidine-4- carboxylate (1.00 g, 4.83 mmol) and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl- 1,3,2-dioxaborolane (1.21 g, 5.79 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 2-chloro-6-(3,6-dihydro-2H-pyran-4- yl)pyrimidine-4-carboxylic acid methyl ester (806 mg, 3.16 mmol).1H NMR (500 MHz, dmso-d6) δ ppm 8.1 (br s, 1H), 7.33 (br s, 1H), 4.34 (br s, 2H), 3.94 (br s, 3H), 3.83 (br s, 2H), 2.53 (m, 2H). Step B: Preparation of 2-cyclopropyl-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid 2-cyclopropyl-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid was prepared according to General Procedure 2C using 2-chloro-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine- 4-carboxylic acid methyl ester (806 mg, 3.16mmol) and cyclopropylboronic acid (571 mg, 6.64 mmol) to give the crude 2-cyclopropyl-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4- carboxylic acid (458 mg, 1.86 mmol). Step C: Preparation of N-[2-[4-[(1R)-1-[[2-cyclopropyl-6-(3,6-dihydro-2H-pyran-4- yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert- butyl ester N-[2-[4-[(1R)-1-[[2-cyclopropyl-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.760 mmol) and 2-cyclopropyl-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carboxylic acid (187 mg, 0.760 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[2-cyclopropyl-6-(3,6-dihydro-2H- pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (473 mg, 0.759 mmol). Step D: Preparation of Example 35 Example 35 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[2- cyclopropyl-6-(3,6-dihydro-2H-pyran-4-yl)pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (473 mg, 0.759 mmol) and trifluoroacetic acid (7.59 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 35 (162 mg, 0.310 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.1 (d, 1H), 7.84 (d, 1H), 7.77 (s, 1H), 7.71 (m, 1H), 7.52 (d, 2H), 7.44 (m, 1H), 7.38 (d, 2H), 7.15 (m, 1H), 5.26 (quin, 1H), 4.3 (br d, 2H), 3.82 (t, 2H), 3.68 (s, 2H), 2.51 (br s, 2H), 2.32 (m, 1H), 1.86 (m, 2H), 1.6 (m, 3H), 1.13 (m, 4H). [M+H]+=523.2312 Example 36: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- tetrahydropyran-4-yl-picolinamide   Step A: Preparation of 4-(3,6-dihydro-2H-pyran-4-yl)picolinic acid methyl ester 4-(3,6-dihydro-2H-pyran-4-yl)picolinic acid methyl ester was prepared according to General Procedure 2A using methyl 4-bromopyridine-2-carboxylate (800 mg, 3.70 mmol) and 2-(3,6- dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.16 g, 5.55 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to give 4-(3,6-dihydro-2H-pyran-4-yl)picolinic acid methyl ester (680 mg, 3.10 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.68 (d, 1H), 8.04 (d, 1H), 7.69 (d, 1H), 6.7 (m, 1H), 4.27 (q, 2H), 3.89 (s, 3H), 3.84 (m, 2H), 2.48 (m, 2H). Step B: Preparation of 4-tetrahydropyran-4-ylpicolinic acid methyl ester 4-tetrahydropyran-4-ylpicolinic acid methyl ester was prepared according to General Procedure 7A using 4-(3,6-dihydro-2H-pyran-4-yl)picolinic acid methyl ester (680 mg, 3.10 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to give 4-tetrahydropyran-4-ylpicolinic acid methyl ester (200 mg, 0.904 mmol). Step C: Preparation of 4-tetrahydropyran-4-ylpicolinic acid 4-tetrahydropyran-4-ylpicolinic acid was prepared according to General Procedure 4A using 4-tetrahydropyran-4-ylpicolinic acid methyl ester (200 mg, 0.904 mmol) to give 4- tetrahydropyran-4-ylpicolinic acid (180 mg, 0.869 mmol). The compound was engaged into the next step without further purification. Step D: Preparation of N-[2-[4-[(1R)-1-[(4-tetrahydropyran-4- ylpicolinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(4-tetrahydropyran-4-ylpicolinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl) benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6B using Intermediate 1 (343 mg, 0.869 mmol) and 4-tetrahydropyran-4-ylpicolinic acid (180 mg, 0.869 mmol) in tetrahydrofuran (2.90 mL). The crude residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to give N-[2-[4-[(1R)-1-[(4- tetrahydropyran-4-ylpicolinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (390 mg, 0.670 mmol). Step E: Preparation of Example 36 Example 36 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(4- tetrahydropyran-4-ylpicolinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (390 mg, 0.668 mmol) and trifluoroacetic acid (13.1 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 36 (220 mg, 0.455 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.09 (d, 1H), 8.59 (d, 1H), 7.92 (d, 1H), 7.84 (d, 1H), 7.71 (dd, 1H), 7.52 (m, 3H), 7.44 (s, 1H), 7.36 (d, 2H), 5.25 (quin, 1H), 3.96 (dd, 2H), 3.67 (s, 2H), 3.44 (m, 2H), 2.94 (tt, 1H), 1.91 (br d, 2H), 1.7 (m, 4H), 1.58 (m, 3H). [M+H]+=484.2204 Example 37: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- (3,6-dihydro-2H-pyran-4-yl)picolinamide Step A: Preparation of lithium;4-(3,6-dihydro-2H-pyran-4-yl)picolinate lithium;4-(3,6-dihydro-2H-pyran-4-yl)picolinate was prepared according to General Procedure 4B using 4-(3,6-dihydro-2H-pyran-4-yl)picolinic acid methyl ester (400 mg, 1.83 mmol) to give lithium;4-(3,6-dihydro-2H-pyran-4-yl)picolinate (385 mg, 1.83 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step B: Preparation of N-[2-[4-[(1R)-1-[[4-(3,6-dihydro-2H-pyran-4- yl)picolinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-(3,6-dihydro-2H-pyran-4-yl)picolinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;4-(3,6-dihydro-2H- pyran-4-yl)picolinate (161 mg, 0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[4-(3,6- dihydro-2H-pyran-4-yl)picolinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (442 mg, 0.760 mmol). Step C: Preparation of Example 37 Example 37 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-(3,6- dihydro-2H-pyran-4-yl)picolinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (442 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 37 (216 mg, 0.449 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.11 (d, 1H), 8.63 (d, 1H), 8.03 (d, 1H), 7.84 (d, 1H), 7.69 (m, 2H), 7.52 (d, 2H), 7.44 (d, 1H), 7.37 (d, 2H), 6.7 (br s, 1H), 5.26 (quin, 1H), 4.27 (d, 2H), 3.84 (t, 2H), 3.68 (s, 2H), 2.47 (m, 2H), 1.99 (m, 2H), 1.58 (d, 3H). [M+H]+=482.2047 Example 38: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- morpholino-picolinamide Step A: Preparation of 4-morpholinopicolinic acid methyl ester 4-morpholinopicolinic acid methyl ester was prepared according to a modified General Procedure 5 using methyl 4-bromopyridine-2-carboxylate (500 mg, 2.32 mmol), morpholine (242 mg, 2.78 mmol) and cesium carbonate (1.51 g, 4.63 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4- morpholinopicolinic acid methyl ester (438 mg, 1.97 mmol). Step B: Preparation of lithium;4-morpholinopicolinate lithium;4-morpholinopicolinate was prepared according to General Procedure 4B using 4- morpholinopicolinic acid methyl ester (438 mg, 1.97 mmol) to give lithium;4- morpholinopicolinate (422 mg, 1.97 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2-[4-[(1R)-1-[(4-morpholinopicolinoyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(4-morpholinopicolinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and lithium;4-morpholinopicolinate (163 mg, 0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[(4-morpholinopicolinoyl)amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (444 mg, 0.760 mmol). Step D: Preparation of Example 38 Example 38 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(4- morpholinopicolinoyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (444 mg, 0.760 mmol) and trifluoroacetic acid (7.60 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 38 (137 mg, 0.283 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.95 (d, 1H), 8.26 (d, 1H), 7.83 (s, 1H), 7.71 (dd, 1H), 7.43 (m, 6H), 7.01 (dd, 1H), 5.21 (m, 1H), 3.71 (br d, 4H), 3.67 (s, 2H), 3.34 (m, 4H), 2.06 (m, 2H), 1.56 (d, 3H). [M+H]+=485.2156 Example 39: N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]nicotinamide   Step A: Preparation of N-[2-[4-[(1R)-1-nicotinamidoethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-nicotinamidoethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert- butyl ester was prepared according to General Procedure 6A using Intermediate 1 (200 mg, 0.507 mmol) and nicotinic acid (62 mg, 0.507 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1- nicotinamidoethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (253 mg, 0.507 mmol). Step B: Preparation of Example 39 Example 39 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1- nicotinamidoethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (253 mg, 0.507 mmol) and trifluoroacetic acid (5.07 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 39 (161 mg, 0.403 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (m, 2H), 8.72 (dd, 1H), 8.24 (dt, 1H), 7.85 (d, 1H), 7.71 (d, 1H), 7.53 (m, 1H), 7.5 (d, 2H), 7.45 (d, 1H), 7.38 (d, 2H), 5.26 (quin, 1H), 3.68 (s, 2H), 2 (br s, 2H), 1.54 (d, 3H). [M+H]+=400.1629 Example 40: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]thiophene-2-carboxamide   Step A: Preparation of 4-(5-carbomethoxy-3-thienyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester 4-(5-carbomethoxy-3-thienyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester was prepared according to General Procedure 2A using methyl 4-bromothiophene-2-carboxylate (1.00 g, 4.52 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6- dihydro-2H-pyridine-1-carboxylate (1.68 g, 5.43 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 4-(5-carbomethoxy-3- thienyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.46 mg, 4.51 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 7.99 (d, 1H), 7.8 (d, 1H), 6.3 (br s, 1H), 3.97 (br d, 2H), 3.83 (s, 3H), 3.51 (t, 2H), 2.43 (m, 2H), 1.42 (m, 9H). Step B: Preparation of 4-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid methyl ester 4-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2-carboxylic acid methyl ester was prepared according to General Procedure 3A using 4-(5-carbomethoxy-3-thienyl)-3,6-dihydro-2H- pyridine-1-carboxylic acid tert-butyl ester (500 mg, 1.55 mmol) and trifluoroacetic acid (15.5 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 4-(1,2,3,6-tetrahydropyridin-4-yl)thiophene-2- carboxylic acid methyl ester (307 mg, 1.38 mmol). Step C: Preparation of 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]thiophene-2- carboxylic acid methyl ester 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]thiophene-2-carboxylic acid methyl ester was prepared according to General Procedure 6A using 4-(1,2,3,6-tetrahydropyridin-4- yl)thiophene-2-carboxylic acid methyl ester (307 mg, 1.38 mmol) and Intermediate 2 (171 mg, 1.38 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- yl]thiophene-2-carboxylic acid methyl ester (422 mg, 1.38 mmol). Step D: Preparation of lithium;4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]-2- thenoate lithium;4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]-2-thenoate was prepared according to General Procedure 4B using 4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin- 4-yl]thiophene-2-carboxylic acid methyl ester (422 mg, 1.37 mmol) to give lithium;4-[1- (oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]-2-thenoate (410 mg, 1.37 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step E: Preparation of N-[2-[4-[(1R)-1- [1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin- 4-yl]thiophene-2-carbonyl]amino]ethyl] -4-(trifluoromethyl)benzyl]carbamic acid tert- butyl ester N-[2-[4-[(1R)-1-[[4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]thiophene-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (250 mg, 0.634 mmol) and lithium;4-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]-2-thenoate (190 mg, 0.634 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[4-[1-(oxetane-3-carbonyl)-3,6- dihydro-2H-pyridin-4-yl]thiophene-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (424 mg, 0.633 mmol). Step F: Preparation of Example 40 Example 40 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[1- (oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]thiophene-2-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (424 mg, 0.633 mmol) and trifluoroacetic acid (6.33 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give Example 40 (25.0 mg, 0.0434 mmol). 1H NMR (400 MHz, dmso-d6) δ ppm 8.85 (d, 1H), 8.16 (s, 1H), 7.83 (s, 1H), 7.71 (d, 1H), 7.63 (s, 1H), 7.43 (m, 5H), 6.17 (m, 1H), 5.19 (m, 1H), 4.7 (m, 4H), 4.23 (m, 1H), 4.14 (br d, 2H), 3.7 (s, 1H), 3.68 (s, 2H), 3.39 (m, 1H), 2.45 (m, 2H), 1.53 (d, 3H). [M+H]+=570.2031 -5- Step A: Preparation of 5-(1-methylpyrazol-4-yl)nicotinic acid methyl ester 5-(1-methylpyrazol-4-yl)nicotinic acid methyl ester was prepared according to a modified General Procedure 2B using methyl 5-bromopyridine-3-carboxylate (500 mg, 2.32 mmol), 1- methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (578 mg, 2.78 mmol), palladium triphenylphosphine (134 mg, 0.116 mmol) and potassium carbonate (959 mg, 6.94 mmol) in a 4:11,4-dioxane / water mixture (16.1 mL). The crude residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to give 5-(1- methylpyrazol-4-yl)nicotinic acid methyl ester (260 mg, 1.20 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (d, 1H), 8.89 (d, 1H), 8.41 (m, 1H), 8.39 (m, 1H), 8.07 (s, 1H), 3.9 (m, 6H). Step B: Preparation of 5-(1-methylpyrazol-4-yl)nicotinic acid 5-(1-methylpyrazol-4-yl)nicotinic acid was prepared according to a modified General Procedure 4A using 5-(1-methylpyrazol-4-yl)nicotinic acid methyl ester (260 mg, 1.20 mmol). The obtained solid was filtered, washed with water and dried under vacuum to give 5- (1-methylpyrazol-4-yl)nicotinic acid (210 mg, 1.00 mmol). The compound was engaged into the next step without further purification.1H NMR (400 MHz, dmso-d6) δ ppm 13.44 (br s, 1H), 9.04 (d, 1H), 8.87 (d, 1H), 8.39 (s, 1H), 8.37 (t, 1H), 8.06 (d, 1H), 3.89 (s, 3H). Step C: Preparation of N-[2-[4-[(1R)-1-[[5-(1-methylpyrazol-4- yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-(1-methylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to a modified General Procedure 6A using Intermediate 1 (388 mg, 0.984 mmol) and 5-(1-methylpyrazol-4- yl)nicotinic acid (200 mg, 0.984 mmol) in tetrahydrofuran (3.28 mL). The crude residues were purified by silica gel column chromatography (ethyl acetate / ethanol) to give N-[2-[4- [(1R)-1-[[5-(1-methylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (520 mg, 0.900 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.06 (d, 1H), 8.96 (d, 1H), 8.86 (m, 1H), 8.37 (t, 1H), 8.33 (s, 1H), 8.03 (s, 1H), 7.75 (br d, 1H), 7.59 (br d, 1H), 7.53 (d, 2H), 7.48 (s, 2H), 7.39 (br d, 2H), 5.28 (quin, 1H), 4.13 (br d, 2H), 3.9 (s, 3H), 1.57 (d, 3H), 1.37 (s, 9H). Step D: Preparation of Example 41 Example 41 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-(1- methylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (520 mg, 0.897 mmol) and trifluoroacetic acid (13.1 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 41 (300 mg, 0.600 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.06 (d, 1H), 8.96 (d, 1H), 8.86 (d, 1H), 8.37 (t, 1H), 8.33 (s, 1H), 8.03 (d, 1H), 7.85 (d, 1H), 7.73 (d, 1H), 7.52 (d, 2H), 7.46 (d, 1H), 7.39 (d, 2H), 5.28 (quin, 1H), 3.9 (s, 3H), 3.72 (s, 2H), 2.98 (br s, 2H), 1.57 (d, 3H). [M+H]+=480.2002

[0008] Example 42: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- (1-isopropylpyrazol-4-yl)nicotinamide   Step A: Preparation of 5-(1-isopropylpyrazol-4-yl)nicotinic acid 5-(1-isopropylpyrazol-4-yl)nicotinic acid was prepared according to a modified General Procedure 2B using methyl 5-bromopyridine-3-carboxylate (500 mg, 2.32 mmol), 1- isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (656 mg, 2.78 mmo), potassium carbonate (960 mg, 6.94 mmol), in a 3:11,4-dioxane / water mixture (16 mL) and the system was heated to 100 °C. After completion of the reaction, aqueous 1 N sodium hydroxide (1.00 mL) was added and the mixture was stirred until complete conversion towards the carboxylic acid. The mixture was filtered and partitioned between ethyl acetate and water. The layers were separated and aqueous 1 N hydrogen chloride (1.00 mL) was added to the aqueous layer until pH=2. The resulting aqueous layer was freeze-dried to give 5-(1-isopropylpyrazol-4-yl)nicotinic acid (1.80 g, 7.80 mmol), which was used into the next step without further purification.1H NMR (400 MHz, dmso-d6) δ ppm 9.18 (d, 1H), 8.92 (s, 1H), 8.65 (t, 1H), 8.62 (s, 1H), 8.16 (s, 1H), 4.53 (spt, 1H), 1.47 (d, 6H). Step B: Preparation of N-[2-[4-[(1R)-1- (1-isopropylpyrazol-4- yl)nicotinoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-(1-isopropylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6B using tert-butylN-[[2-[4-[(1R)-1-aminoethyl]phenyl]-4-(trifluoromethyl) phenyl]methyl]carbamate (259 mg, 0.649 mmol) and 5-(1-isopropylpyrazol-4-yl)nicotinic acid (150 mg, 0.649 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / ethanol / ammoniac) to give N-[2-[4-[(1R)-1-[[5-(1- isopropylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (170 mg, 0.28 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.06 (d, 1H), 8.98 (d, 1H), 8.85 (d, 1H), 8.42 (s, 1H), 8.38 (t, 1H), 8.04 (s, 1H), 7.75 (br d, 1H), 7.59 (br d, 1H), 7.53 (d, 2H), 7.48 (m, 2H), 7.39 (br d, 2H), 5.28 (quin, 1H), 4.54 (spt, 1H), 4.13 (br d, 2H), 1.57 (d, 3H), 1.46 (d, 6H), 1.37 (s, 9H). Step C: Preparation of Example 42 Example 42 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-(1- isopropylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (170 mg, 0.28 mmol) and trifluoroacetic acid (8.00 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 42 (114 mg, 0.225 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.05 (d, 1H), 8.98 (d, 1H), 8.85 (d, 1H), 8.43 (s, 1H), 8.38 (t, 1H), 8.04 (s, 1H), 7.85 (d, 1H), 7.72 (d, 1H), 7.51 (d, 2H), 7.46 (s, 1H), 7.39 (d, 2H), 5.28 (quin, 1H), 4.54 (spt, 1H), 3.71 (s, 2H), 2.58 (m, 1H), 1.57 (d, 3H), 1.46 (d, 6H). [M+H]+=508.2328 Example 43: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- (1-cyclopropylpyrazol-4-yl)nicotinamide   Step A: Preparation of 5-(1-cyclopropylpyrazol-4-yl)nicotinic acid 5-(1-cyclopropylpyrazol-4-yl)nicotinic acid was prepared according to a modified General Procedure 2B using methyl 5-bromopyridine-3-carboxylate (500 mg, 2.32 mmol), 1- cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (650 mg, 2.78 mmol), potassium carbonate (960 mg, 6.94 mmol), in a 3:11,4-dioxane / water mixture (16 mL) and the system was heated to 100 °C. After completion of the reaction, aqueous 1 N sodium hydroxide (1.00 mL) was added and the mixture was stirred until complete conversion towards the carboxylic acid. The mixture was filtered and partitioned between ethyl acetate and water. The layers were separated and aqueous 1 N hydrogen chloride (1.00 mL) was added to the aqueous layer until pH=2. The aqueous layer was freeze-dried to give 5-(1- cyclopropylpyrazol-4-yl)nicotinic acid (2.00 g, 8.72 mmol), which was used into the next step without further purification.1H NMR (400 MHz, dmso-d6) δ ppm 9.11 (d, 1H), 8.9 (d, 1H), 8.56 (s, 1H), 8.53 (t, 1H), 8.11 (s, 1H), 3.77 (tt, 1H), 1.05 (m, 4H). Step B: Preparation of N-[2-[4-[(1R)-1- (1-cyclopropylpyrazol-4- yl)nicotinoyl]amino]ethyl]phenyl]-4- benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-(1-cyclopropylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6B using tert-butylN-[[2-[4-[(1R)-1-aminoethyl]phenyl]-4-(trifluoromethyl) phenyl]methyl]carbamate (259 mg, 0.649 mmol) and 5-(1-cyclopropylpyrazol-4-yl)nicotinic acid (150 mg, 0.654 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / ethanol / ammoniac) to give N-[2-[4-[(1R)-1-[[5-(1- isopropylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (260 mg, 0.43 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.05 (d, 1H), 8.97 (d, 1H), 8.86 (d, 1H), 8.44 (s, 1H), 8.38 (t, 1H), 8.03 (s, 1H), 7.75 (br d, 1H), 7.59 (m, 1H), 7.52 (d, 2H), 7.47 (m, 2H), 7.39 (br d, 2H), 5.28 (quin, 1H), 4.13 (br d, 2H), 3.78 (tt, 1H), 1.57 (d, 3H), 1.37 (s, 9H), 1.12 (m, 2H), 1 (m, 2H). Step C: Preparation of Example 43 Example 43 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-(1- cyclopropylpyrazol-4-yl)nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (260 mg, 0.43 mmol) and trifluoroacetic acid (13.1 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 43 (130 mg, 0.26 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.04 (d, 1H), 8.97 (d, 1H), 8.86 (d, 1H), 8.44 (s, 1H), 8.38 (t, 1H), 8.03 (s, 1H), 7.85 (d, 1H), 7.71 (d, 1H), 7.51 (d, 2H), 7.45 (d, 1H), 7.39 (d, 2H), 5.28 (quin, 1H), 3.78 (tt, 1H), 3.69 (s, 2H), 1.98 (br s, 2H), 1.57 (d, 3H), 1.05 (m, 4H). [M+H]+=506.2130 (δ=-6.4 ppm). Example 44: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [4-[[(2S)-oxetan-2-yl]methyl]piperazino]nicotinamide   Step A: Preparation of 5-[4-[[(2S)-oxetan-2-yl]methyl]piperazino]nicotinic acid methyl ester To a solution of Intermediate 3 (272 mg, 1.23 mmol) in acetonitrile (5.00 mL) were added potassium carbonate (153 mg, 1.11 mmol) and (2S)-2-(bromomethyl)oxetane (204 mg, 1.35 mmol) and the mixture was heated to 80 °C. After completion of the reaction, water was added and the aqueous layer was extracted with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 5-[4-[[(2S)-oxetan-2-yl]methyl]piperazino]nicotinic acid methyl ester (190 mg, 0.652 mmol). Step B: Preparation of lithium;5-[4-[[ -oxetan-2-yl]methyl]piperazino]nicotinate Lithium;5-[4-[[(2S)-oxetan-2-yl] nicotinate was prepared according to General Procedure 4B using 5-[4-[[(2S)-oxetan-2-yl]methyl]piperazino]nicotinic acid methyl ester (190 mg, 0.652 mmol) to give lithium;5-[4-[[(2S)-oxetan-2- yl]methyl]piperazino]nicotinate (184 mg, 0.652 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step C: Preparation of N-[2- -oxetan-2-yl]methyl]piperazino] nicotinoyl]amino]ethyl] - carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[4-[[(2S)-oxetan-2-yl]methyl]piperazino]nicotinoyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (230 mg, 0.583 mmol) and lithium;5-[4-[[(2S)-oxetan-2- yl]methyl]piperazino]nicotinate (165 mg, 0.583 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[5- [4-[[(2S)-oxetan-2-yl]methyl]piperazino]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (381 mg, 0.583 mmol). Step D: Preparation of Example 44 Example 45 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[4- [[(2S)-oxetan-2-yl]methyl]piperazino]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl) benzyl]carbamic acid tert-butyl ester (264 mg, 0.612 mmol) and trifluoroacetic acid (5.81 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 44 (150 mg, 0.466 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.95 (d, 1H), 8.48 (d, 1H), 8.41 (d, 1H), 7.85 (d, 1H), 7.7 (m, 2H), 7.48 (m, 2H), 7.44 (d, 1H), 7.38 (d, 2H), 5.25 (quin, 1H), 4.93 (qd, 1H), 4.51 (td, 1H), 4.39 (dt, 1H), 3.68 (s, 2H), 3.25 (m, 4H), 2.69 (m, 1H), 2.59 (m, 6H), 2.38 (ddt, 1H), 1.99 (m, 2H), 1.54 (d, 3H). [M+H]+=554.2734 Example 45: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- [1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinamide   Step A: Preparation of 6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazinic acid methyl ester 6-(1-Tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazinic acid methyl ester was prepared according to General Procedure 2A using methyl 6-bromopyrazine-2-carboxylate (1.00 g, 4.61 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6- dihydro-2H-pyridine-1-carboxylate (1.71 g, 5.53 mmol ). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 6-(1,2,3,6- tetrahydropyridin-4-yl)pyrazinic acid methyl ester (1.40 g, 4.40 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.08 (m, 2H), 6.92 (br s, 1H), 4.11 (br d, 2H), 3.93 (s, 3H), 3.57 (t, 2H), 2.62 (m, 2H), 1.43 (s, 9H). Step B: Preparation of 6-(1,2,3,6-tetrahydropyridin-4-yl)pyrazinic acid methyl ester 6-(1,2,3,6-Tetrahydropyridin-4-yl)pyrazinic acid methyl ester was prepared according to General Procedure 3A using 6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazinic acid methyl ester (650 mg, 2.04 mmol) and trifluoroacetic acid (20.4 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 6-(1,2,3,6-tetrahydropyridin-4-yl)pyrazinic acid methyl ester (307 mg, 1.40 mmol), which was used into the next step without further purification. Step C: Preparation of 6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinic acid methyl ester 6-[1-(Oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinic acid methyl ester was prepared according to General Procedure 6A using 6-(1,2,3,6-tetrahydropyridin-4- yl)pyrazinic acid methyl ester (307 mg, 1.40 mmol) and Intermediate 2 (174 mg, 1.40 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- yl]pyrazinic acid methyl ester (379 mg, 1.25 mmol). of lithium;6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- Lithium;6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinate was prepared according to General Procedure 4B using 6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin- 4-yl]pyrazinic acid methyl ester (379 mg, 1.25 mmol) to give lithium;6-[1-(oxetane-3- carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinate (368 mg, 1.25 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step E: Preparation of N-[2- -1-[[6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin- 4-yl]pyrazinoyl]amino]ethyl] -4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinoyl]amino] ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using lithium;6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4- yl]pyrazinate (172 mg, 0.583 mmol) and Intermediate 1 (230mg, 0.583 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[6-[1-(oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinoyl] amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (388 mg, 0.583 mmol). Step F: Preparation of Example 45 Example 45 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[6-[1- (oxetane-3-carbonyl)-3,6-dihydro-2H-pyridin-4-yl]pyrazinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (388 mg, 0.583 mmol) and trifluoroacetic acid (5.83 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 46 (18.0 mg, 0.0550 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.01 (m, 2H), 8.75 (m, 1H), 7.81 (m, 1H), 7.66 (m, 1H), 7.52 (m, 2H), 7.41 (m, 1H), 7.36 (m, 2H), 7 (m, 1H), 5.3 (m, 1H), 4.72 (m, 4H), 4.11 (m, 4H), 3.69 (m, 2H), 3.45 (m, 1H), 2.72 (m, 2H), 1.63 (m, 5H). [M+H]+=566.2377

[0009] Step A: Preparation of 6-(1-tert-butoxycarbonyl-4-piperidyl)pyrazinic acid methyl ester 6-(1-tert-butoxycarbonyl-4-piperidyl)pyrazinic acid methyl ester was prepared according to General Procedure 7B using 6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazinic acid methyl ester (700 mg, 2.19 mmol). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 6-(1-tert-butoxycarbonyl-4- piperidyl)pyrazinic acid methyl ester (419 mg, 0.595 mmol). Step B: Preparation of 6-(4-piperidyl)pyrazinic acid methyl ester 6-(4-piperidyl)pyrazinic acid methyl ester was prepared according to General Procedure 3A using 6-(1-tert-butoxycarbonyl-4-piperidyl)pyrazinic acid methyl ester (419 mg, 1.30 mmol) and trifluoroacetic acid (13.0 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a porapak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give 6-(4-piperidyl)pyrazinic acid methyl ester (209 mg, 0.725 mmol). Step C: Preparation of 6-[1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinic acid methyl ester 6-[1-(Oxetane-3-carbonyl)-4-piperidyl]pyrazinic acid methyl ester was prepared according to General Procedure 6A using 6-(4-piperidyl)pyrazinic acid methyl ester (209 g, 0.945 mmol) and Intermediate 2 (117 mg, 0.945 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 6-[1-(oxetane-3-carbonyl)-4- piperidyl]pyrazinic acid methyl ester (50.0 mg, 0.164 mmol). Step D: Preparation of lithium;6-[1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinate Lithium;6-[1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinate was prepared according to General Procedure 4B using 6-[1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinic acid methyl ester (50.0 mg, 0.164 mmol) to give lithium;6-[1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinate (48.0 mg, 0.162 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step E: Preparation of N-[2-[4-[(1R)-1- [1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinoyl] amino]ethyl]phenyl]-4- carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[6-[1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (65.0 mg, 0.165 mmol) and lithium;6-[1-(oxetane-3- carbonyl)-4-piperidyl]pyrazinate (49.0 mg, 0.165 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1-[[6- [1-(oxetane-3-carbonyl)-4-piperidyl]pyrazinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (110 mg, 0.165 mmol). Step F: Preparation of Example 46 Example 46 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[6-[1- (oxetane-3-carbonyl)-4-piperidyl]pyrazinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl] carbamic acid tert-butyl ester (110 mg, 0.615 mmol) and trifluoroacetic acid (1.65 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give Example 46 (18.0 mg, 0.0317 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.04 (m, 2H), 8.83 (m, 1H), 7.84 (m, 1H), 7.72 (m, 1H), 7.52 (m, 2H), 7.45 (m, 1H), 7.37 (m, 2H), 5.3 (m, 1H), 4.71 (m, 4H), 4.58 (m, 1H), 4.15 (m, 1H), 3.68 (m, 2H), 3.51 (m, 1H), 3.17 (m, 1H), 3.08 (m, 1H), 2.74 (m, 1H), 1.95 (m, 2H), 1.76 (m, 2H), 1.61 (m, 3H). [M+H]+=568.2534 -4- Step A: Preparation of 4-(5-carbomethoxy-3-thienyl)piperidine-1-carboxylic acid tert-butyl ester 4-(5-Carbomethoxy-3-thienyl)piperidine-1-carboxylic acid tert-butyl ester was prepared according to a modified General Procedure 7B using 4-(5-carbomethoxy-3-thienyl)-3,6- dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.23 g, 3.80 mmol). Ammonium formate and palladium on carbon were added several times until completion of the reaction. The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 4-(5-carbomethoxy-3-thienyl)piperidine-1-carboxylic acid tert-butyl ester (775 mg, 2.38 mmol). Step B: Preparation of 4-(4-piperidyl)thiophene-2-carboxylic acid methyl ester 4-(4-Piperidyl)thiophene-2-carboxylic acid methyl ester was prepared according to General Procedure 3A using 4-(5-carbomethoxy-3-thienyl)piperidine-1-carboxylic acid tert-butyl ester (775 mg, 2.38 mmol) and trifluoroacetic acid (23.8 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give 4-(4-piperidyl)thiophene-2-carboxylic acid methyl ester (419 mg, 1.86 mmol). Step C: Preparation of 4-[1-(oxetane-3-carbonyl)-4-piperidyl]thiophene-2-carboxylic acid methyl ester 4-[1-(Oxetane-3-carbonyl)-4-piperidyl]thiophene-2-carboxylic acid methyl ester was prepared according to General Procedure 6A using 4-(4-piperidyl)thiophene-2-carboxylic acid methyl ester (419 mg, 1.86 mmol) and Intermediate 2 (231 mg, 1.86 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give 4-[1- (oxetane-3-carbonyl)-4-piperidyl]thiophene-2-carboxylic acid methyl ester (330 mg, 1.07 mmol). Step D: Preparation of lithium;4-[1-(oxetane-3-carbonyl)-4-piperidyl]-2-thenoate Lithium;4-[1-(oxetane-3-carbonyl)-4-piperidyl]-2-thenoate was prepared according to General Procedure 4B using 4-[1-(oxetane-3-carbonyl)-4-piperidyl]thiophene-2-carboxylic acid methyl ester (330 mg, 1.07 mmol) to give lithium;4-[1-(oxetane-3-carbonyl)-4-piperidyl]-2- thenoate (321 mg, 1.07 mmol), considering a quantitative yield. The compound was engaged into the next step without further purification. Step E: Preparation of N-[2- (oxetane-3-carbonyl)-4-piperidyl]thiophene-2- carbonyl]amino]ethyl] - benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[4-[1-(oxetane-3-carbonyl)-4-piperidyl]thiophene-2-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (210 mg, 0.533 mmol) and lithium;4-[1-(oxetane- 3-carbonyl)-4-piperidyl]-2-thenoate (161 mg, 0.533 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2-[4-[(1R)-1- [[4-[1-(oxetane-3-carbonyl)-4-piperidyl]thiophene-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (357 mg, 0.531 mmol). Step F: Preparation of Example 47 Example 48 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[4-[1- (oxetane-3-carbonyl)-4-piperidyl]thiophene-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (357 mg, 0.531 mmol) and trifluoroacetic acid (5.31 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give Example 47 (39.0 mg, 0.0682 mmol). 1H NMR (400 MHz, dmso-d6) δ ppm 8.74 (d, 1H), 7.87 (d, 2H), 7.71 (dd, 1H), 7.43 (m, 6H), 5.18 (quin, 1H), 4.7 (br d, 4H), 4.5 (m, 1H), 4.13 (m, 1H), 3.68 (s, 2H), 3.44 (br d, 1H), 3.04 (m, 1H), 2.85 (s, 1H), 2.68 (m, 1H), 2.02 (m, 2H), 1.88 (m, 2H), 1.52 (d, 3H), 1.43 (br d, 2H). [M+H]+=572.2192 Example 48: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4-carboxamide   Step A: Preparation of 2-chloro-6-tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid methyl ester To a stirred solution of methyl 2,6-dichloropyrimidine-4-carboxylate (1.00 g, 4.83 mmol) and tetrakis(triphenylphosphine)-palladium (782 mg, 0.676 mmol, 14 mol%) in tetrahydrofuran (22.0 mL) was added dropwise a 0.5 M tetrahydro-2H-pyran-4-yl)zinc (II) iodide solution in tetrahydrofuran (18.8 mL) at room temperature under a nitrogen atmosphere. The resulting solution was heated to 50 °C until completion of the reaction. Water was added and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 2-chloro-6-tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid methyl ester (604 mg, 2.35 mmol).1H NMR (500 MHz, dmso-d6) δ ppm 7.98 (m, 1H), 3.94 (m, 2H), 3.93 (m, 3H), 3.43 (m, 2H), 3.14 (m, 1H), 1.77 (m, 4H). Step B: Preparation of 2-cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid 2-cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid was prepared according to General Procedure 2C using 2-chloro-6-tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid methyl ester (600 mg, 2.34 mmol) and cyclopropylboronic acid (422 mg, 4.91 mmol) to give the crude 2-cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid (220 mg, 0.886 mmol). Step C: Preparation of N-[2-[4-[(1R)-1-[(2-cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(2-cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4-carbonyl)amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and 2-cyclopropyl-6- tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid (189 mg, 0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2- [4-[(1R)-1-[(2-cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4-carbonyl)amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (357 mg, 0.572 mmol). Step D: Preparation of Example 48 Example 48 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(2- cyclopropyl-6-tetrahydropyran-4-yl-pyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (357 mg, 0.572 mmol) and trifluoroacetic acid (5.72 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 48 (70.0 mg, 0.133 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (d, 1H), 7.83 (s, 1H), 7.72 (br d, 1H), 7.61 (s, 1H), 7.51 (d, 2H), 7.44 (d, 1H), 7.38 (d, 2H), 5.25 (m, 1H), 3.94 (m, 2H), 3.68 (s, 2H), 3.43 (td, 2H), 2.98 (m, 1H), 2.31 (m, 1H), 2.07 (m, 2H), 1.73 (m, 4H), 1.59 (m, 3H), 1.12 (m, 4H). [M+H]+=525.2484 Example 49: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- cyclopropyl-2-tetrahydropyran-4-yl-pyrimidine-4-carboxamide   Step A: Preparation of 6-cyclopropyl-2-tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid To a stirred solution of 2-chloro-6-cyclopropyl-pyrimidine-4-carboxylic acid methyl ester (250 mg, 1.18 mmol) and tetrakis(triphenylphosphine)-palladium (190 mg, 0.165 mmol, 14 mol%) in tetrahydrofuran (5.30 mL) was added dropwise a 0.5 M tetrahydro-2H-pyran-4- yl)zinc (II) iodide solution in tetrahydrofuran (4.59 mL) at room temperature under a nitrogen atmosphere. The resulting solution was heated to 50 °C until completion of the reaction. Water was added and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give 6-cyclopropyl-2-tetrahydropyran-4-yl- pyrimidine-4-carboxylic acid (180 mg, 0.725 mmol). Step B: Preparation of N-[2-[4-[(1R)-1-[(6-cyclopropyl-2-tetrahydropyran-4-yl-pyrimidine-4- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[(6-cyclopropyl-2-tetrahydropyran-4-yl-pyrimidine-4-carbonyl)amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol) and 6-cyclopropyl-2- tetrahydropyran-4-yl-pyrimidine-4-carboxylic acid (189 mg, 0.761 mmol). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give N-[2- [4-[(1R)-1-[(6-cyclopropyl-2-tetrahydropyran-4-yl-pyrimidine-4-carbonyl)amino]ethyl] phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (90.0 mg, 0.144 mmol). Step C: Preparation of Example 49 Example 49 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[(6- cyclopropyl-2-tetrahydropyran-4-yl-pyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester (90.0 mg, 0.144 mmol) and trifluoroacetic acid (1.44 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 49 (13.0 mg, 0.0248 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.04 (d, 1H), 7.84 (d, 1H), 7.74 (s, 2H), 7.5 (s, 2H), 7.45 (s, 1H), 7.38 (d, 2H), 5.27 (m, 1H), 3.95 (dt, 2H), 3.68 (s, 2H), 3.46 (m, 2H), 3.08 (dt, 1H), 2.26 (m, 1H), 2 (m, 1H), 1.88 (m, 4H), 1.6 (d, 3H), 1.1 (m, 4H). [M+H]+=525.2457 Example 50: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [1-(oxetan-3-yl)pyrazol-4-yl]nicotinamide   Step A: Preparation of 5-[1-(oxetan-3-yl)pyrazol-4-yl]nicotinic acid 5-[1-(Oxetan-3-yl)pyrazol-4-yl]nicotinic acid was prepared according to a modified General Procedure 2B using ethyl 5-bromopyridine-3-carboxylate (500 mg, 2.32 mmol), 1-(oxetan-3- yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (695 mg, 2.78 mmol), potassium carbonate (960 mg, 6.94 mmol), in a 3:11,4-dioxane / water mixture (16 mL) and the system was heated to 100 °C. After completion of the reaction, aqueous 1 N sodium hydroxide (1.00 mL) was added and the mixture was stirred until complete conversion towards the carboxylic acid. The mixture was filtered and partitioned between ethyl acetate and water. The layers were separated and aqueous 1 N hydrogen chloride (1.00 mL) was added to the aqueous layer until pH=2. The resulting aqueous layer was freeze-dried to give 5-[1-(oxetan-3-yl)pyrazol-4- yl]nicotinic acid (3.00 g, 12.2 mmol), which was used into the next step without further purification. Step B: Preparation of N-[2-[4-[(1R)-1-[[5-[1-(oxetan-3-yl)pyrazol-4- yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester N-[2-[4-[(1R)-1-[[5-[1-(oxetan-3-yl)pyrazol-4-yl]nicotinoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)benzyl]carbamic acid tert-butyl ester was prepared according to General Procedure 6B using Intermediate 1 (402 mg, 1.02 mmol) and 5-[1-(oxetan-3-yl)pyrazol-4- yl]nicotinic acid (250 mg, 1.02 mmol). The crude residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give N-[2-[4-[(1R)-1-[[5-[1-(oxetan-3-yl)pyrazol-4- yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (110 mg, 0.177 mmol). Step C: Preparation of Example 50 Example 50 was prepared according to General Procedure 3A using N-[2-[4-[(1R)-1-[[5-[1- (oxetan-3-yl)pyrazol-4-yl]nicotinoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)benzyl]carbamic acid tert-butyl ester (110 mg, 0.177 mmol) and trifluoroacetic acid (13.1 mmol). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (acetonitrile / water / ammonium bicarbonate) to give Example 50 (25.0 mg, 0.0479 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.06 (d, 1H), 9.01 (d, 1H), 8.88 (d, 1H), 8.58 (s, 1H), 8.41 (t, 1H), 8.21 (s, 1H), 7.85 (d, 1H), 7.71 (dd, 1H), 7.51 (d, 2H), 7.45 (d, 1H), 7.39 (d, 2H), 5.62 (quin, 1H), 5.28 (quin, 1H), 4.95 (m, 4H), 3.69 (s, 2H), 1.97 (m, 2H), 1.57 (d, 3H). [M+H]+= 522.2110 Example 51: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- morpholino-pyrazine-2-carboxamide Step A: Preparation of methyl 6-morpholinopyrazine-2-carboxylate Methyl 6-morpholinopyrazine-2-carboxylate was prepared according to General Procedure 5 using methyl 6-bromopyrazine-2-carboxylate (500 mg, 2.30 mmol, 1.0 eq.) and morpholine (242 µL, 2.77 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 6-morpholinopyrazine-2-carboxylate (364 mg, 1.47 mmol). Step B: Preparation of lithium 6-morpholinopyrazine-2-carboxylate Lithium 6-morpholinopyrazine-2-carboxylate was prepared according to General Procedure 4B using methyl 6-morpholinopyrazine-2-carboxylate (364 mg, 1.63 mmol, 1.0 eq.) to give lithium 6-morpholinopyrazine-2-carboxylate (350 mg, 1.63 mmol). The compound was engaged into the next step without further purification. tert-Butyl N-[[2-[4-[(1R)-1-[(6-morpholinopyrazine-2-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol, 1.0 eq.) and lithium 6-morpholinopyrazine-2- carboxylate (164 mg, 0.761 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[(6- morpholinopyrazine-2-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (445 mg, 0.760 mmol). Step D: Preparation of Example 51 Example 51 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[(6-morpholinopyrazine-2-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (445 mg, 0.760 mmol, 1.0 eq.) and trifluoroacetic acid (582 µL, 7.60 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 51 (266 mg, 0.548 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.82 (m, 1H), 8.5 (m, 1H), 8.4 (m, 1H), 7.84 (m, 1H), 7.73 (m, 1H), 7.5 (m, 2H), 7.43 (m, 1H), 7.38 (m, 2H), 5.28 (m, 1H), 3.76 (m, 4H), 3.69 (m, 6H), 1.92 (m, 2H), 1.59 (m, 3H). [M+H]+ = 486.2110. Example 52: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2-carboxamide 3,6-dihydro-2H-pyridin-5- 2-carboxylate Methyl 4-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-5-yl)pyridine-2-carboxylate was prepared according to General Procedure 2A using methyl 4-bromopyridine-2-carboxylate (1.00 g, 4.62 mmol, 1.0 eq.) and tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 3,6-dihydro-2H-pyridine-1-carboxylate (1.72 g, 5.56 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 4-(1-tert- butoxycarbonyl-3,6-dihydro-2H-pyridin-5-yl)pyridine-2-carboxylate (1.05 g, 3.28 mmol). Step B: Preparation of methyl 4-(1,2,3,6-tetrahydropyridin-5-yl)pyridine-2-carboxylate Methyl 4-(1,2,3,6-tetrahydropyridin-5-yl)pyridine-2-carboxylate was prepared according to General Procedure 3A using methyl 4-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-5- yl)pyridine-2-carboxylate (300 mg, 0.942 mmol, 1.0 eq.) and trifluoroacetic acid (721 µL, 9.42 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give methyl 4-(1,2,3,6-tetrahydropyridin-5- yl)pyridine-2-carboxylate (151 mg, 0.692 mmol). Step C: Preparation of methyl 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2- carboxylate: Oxetan-3-one (74.8 mg, 1.01 mmol, 1.5 eq.) and acetic acid (79.2 µL, 1.38 mmol, 2.0 eq.) were added to a methyl 4-(1,2,3,6-tetrahydropyridin-5-yl)pyridine-2-carboxylate (151 mg, 0.692 mmol, 1.0 eq.) solution in THF (10 mL). The reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (440 mg, 7.00 mmol, 10.1 eq.) was added at 0 °C and the mixture was stirred at room temperature until completion of the reaction. The reaction mixture was concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 4-[1- (oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2-carboxylate (103 mg, 0.376 mmol). Step D: Preparation of lithium 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2- carboxylate Lithium 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2-carboxylate was prepared according to General Procedure 4B using methyl 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin- 5-yl]pyridine-2-carboxylate (103 mg, 0.376 mmol, 1.0 eq.) to give lithium 4-[1-(oxetan-3-yl)- 3,6-dihydro-2H-pyridin-5-yl]pyridine-2-carboxylate (99.0 mg, 0.372 mmol). The compound was engaged into the next step without further purification. of tert-butyl N-[[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-3,6-dihydro-2H- -4- tert-Butyl N-[[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6B using Intermediate 1 (147 mg, 0.372 mmol, 1.0 eq.) and lithium 4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2-carboxylate (99 mg, 0.372 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-3,6- dihydro-2H-pyridin-5-yl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (236 mg, 0.371 mmol). Step F: Preparation of Example 52 Example 52 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-[1-(oxetan-3-yl)-3,6-dihydro-2H-pyridin-5-yl]pyridine-2-carbonyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)phenyl]methyl]carbamate (236 mg, 0.371 mmol, 1.0 eq.) and trifluoroacetic acid (284 µL, 3.71 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 52 (75.0 mg, 0.140 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.11 (m, 1H), 8.59 (d, 1H), 7.95 (d, 1H), 7.84 (d, 1H), 7.71 (dd, 1H), 7.63 (dd, 1H), 7.5 (s, 2H), 7.44 (d, 1H), 7.36 (d, 2H), 6.65 (t, 1H), 5.24 (quin, 1H), 4.57 (m, 4H), 3.66 (m, 3H), 3.22 (br d, 2H), 2.43 (m, 2H), 2.34 (br d, 2H), 2.03 (m, 2H), 1.58 (d, 3H). [M+H]+=537.2477. -3- Step A: Preparation of tert-butyl 4-(3-methoxycarbonylphenyl)-3,6-dihydro-2H-pyridine-1- carboxylate tert-Butyl 4-(3-methoxycarbonylphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate was prepared according to General Procedure 2A using methyl 3-bromobenzoate (1.00 g, 4.65 mmol, 1.0 eq.) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H- pyridine-1-carboxylate (1.73 g, 5.58 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give tert-butyl 4-(3- methoxycarbonylphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate (1.40 g, 1.48 mmol). Step B: Preparation of tert-butyl 4-(3-methoxycarbonylphenyl)piperidine-1-carboxylate tert-Butyl 4-(3-methoxycarbonylphenyl)piperidine-1-carboxylate was prepared according to General Procedure 7B using tert-butyl 4-(3-methoxycarbonylphenyl)-3,6-dihydro-2H- pyridine-1-carboxylate (900 mg, 2.84 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give tert-butyl 4-(3- methoxycarbonylphenyl)piperidine-1-carboxylate (900 mg, 2.82 mmol). Step C: Preparation of methyl 3-(4-piperidyl)benzoate Methyl 3-(4-piperidyl)benzoate was prepared according to General Procedure 3A using tert- butyl 4-(3-methoxycarbonylphenyl)piperidine-1-carboxylate (900 mg, 2.82 mmol, 1.0 eq.) and trifluoroacetic acid (2.16 mL, 28.2 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give methyl 3-(4-piperidyl)benzoate (533 mg, 2.43 mmol). Methyl 3-[1-(cyclopropanecarbonyl)-4-piperidyl]benzoate was prepared according to General Procedure 6A using methyl 3-(4-piperidyl)benzoate (300 mg, 1.37 mmol, 1.0 eq.) and cyclopropanecarboxylic acid (118 mg, 1.37 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 3-[1- (cyclopropanecarbonyl)-4-piperidyl]benzoate (390 mg, 1.36 mmol). E: Preparation of lithium 3-[1- Lithium 3-[1-(cyclopropanecarbonyl)-4-piperidyl]benzoate was prepared according to General Procedure 4B using methyl 3-[1-(cyclopropanecarbonyl)-4-piperidyl]benzoate (393 mg, 1.37 mmol, 1.0 eq.) to give lithium 3-[1-(cyclopropanecarbonyl)-4-piperidyl]benzoate (381 mg, 1.36 mmol). The compound was engaged into the next step without further purification. of tert-butyl N-[[2-[4-[(1R)-1-[[3-[1- -4- tert-Butyl N-[[2-[4-[(1R)-1-[[3-[1-(cyclopropanecarbonyl)-4-piperidyl]benzoyl]amino]ethyl] phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (300 mg, 0.761 mmol, 1.0 eq.) and lithium 3-[1- (cyclopropanecarbonyl)-4-piperidyl]benzoate (212 mg, 0.761 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[[3-[1-(cyclopropanecarbonyl)-4-piperidyl]benzoyl]amino] ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate (445 mg, 0.685 mmol). Step G: Preparation of Example 53 Example 53 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[3-[1-(cyclopropanecarbonyl)-4-piperidyl]benzoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (445 mg, 0.685 mmol, 1.0 eq.) and trifluoroacetic acid (524 mL, 6.85 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 53 (248 mg, 0.451 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.83 (d, 1H), 7.83 (m, 2H), 7.76 (d, 1H), 7.72 (br d, 1H), 7.42 (m, 7H), 5.26 (quin, 1H), 4.48 (m, 2H), 3.68 (s, 2H), 3.2 (m, 1H), 2.87 (m, 1H), 2.65 (m, 1H), 2.01 (m, 1H), 1.87 (br s, 4H), 1.54 (d, 3H), 0.72 (m, 4H). [M+H]+ = 550.2644. Example 54: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-3- [1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]benzamide Step A: Preparation of methyl 3-(1,2,3,6-tetrahydropyridin-4-yl)benzoate Methyl 3-(1,2,3,6-tetrahydropyridin-4-yl)benzoate was prepared according to General Procedure 3A using tert-butyl 4-(3-methoxycarbonylphenyl)-3,6-dihydro-2H-pyridine-1- carboxylate (500 mg, 1.58 mmol, 1.0 eq.) and trifluoroacetic acid (1.21 mL, 15.8 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give methyl 3-(1,2,3,6-tetrahydropyridin-4-yl)benzoate (303 mg, 1.39 mmol). Step B: Preparation of methyl 3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4- yl]benzoate Methyl 3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]benzoate was prepared according to General Procedure 6A using methyl 3-(1,2,3,6-tetrahydropyridin-4-yl)benzoate (303 mg, 1.39 mmol, 1.0 eq.) and cyclopropanecarboxylic acid (120 mg, 1.39 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H- pyridin-4-yl]benzoate (397 mg, 1.39 mmol). Step C: Preparation of lithium 3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4- yl]benzoate Lithium 3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]benzoate was prepared according to General Procedure 4B using methyl 3-[1-(cyclopropanecarbonyl)-3,6-dihydro- 2H-pyridin-4-yl]benzoate (397 mg, 1.39 mmol, 1.0 eq.) to give lithium 3-[1- (cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]benzoate (385 mg, 1.39 mmol). The compound was engaged into the next step without further purification. Step D: Preparation of tert-butyl N-[[2-[4-[(1R)-1-[[3-[1-(cyclopropanecarbonyl)-3,6- dihydro-2H-pyridin-4-yl]benzoyl]amino]ethyl]phenyl]-4- tert-Butyl N-[[2-[4-[(1R)-1-[[3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4- yl]benzoyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6B using Intermediate 1 (299 mg, 0.758 mmol, 1.0 eq.) and lithium 3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]benzoate (210 mg, 0.758 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[[3-[1- (cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]benzoyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (490 mg, 0.757 mmol). Step E: Preparation of Example 54 Example 54 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[3-[1-(cyclopropanecarbonyl)-3,6-dihydro-2H-pyridin-4-yl]benzoyl]amino]ethyl]phenyl]- 4-(trifluoromethyl)phenyl]methyl]carbamate (490 mg, 0.757 mmol, 1.0 eq.) and trifluoroacetic acid (579 µL, 7.57 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 54 (104 mg, 0.190 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.9 (d, 1H), 7.97 (s, 1H), 7.83 (dd, 2H), 7.71 (dd, 1H), 7.61 (br d, 1H), 7.49 (m, 3H), 7.44 (m, 1H), 7.38 (d, 2H), 6.29 (br s, 1H), 5.27 (m, 1H), 4.42 (br s, 1H), 4.14 (br s, 1H), 3.91 (br s, 1H), 3.71 (br s, 1H), 3.68 (s, 2H), 2.66 (m, 2H), 1.96 (m, 3H), 1.55 (d, 3H), 0.75 (m, 4H). [M+H]+ = 548.2482. -4- of methyl 4-(1-tert-butoxycarbonyl-3- 2-carboxylate enantiomer 1 Methyl 4-(1-tert-butoxycarbonyl-3-piperidyl)pyridine-2-carboxylate enantiomer 1 was prepared according to General Procedure 7B using methyl 4-(1-tert-butoxycarbonyl-3,6- dihydro-2H-pyridin-5-yl)pyridine-2-carboxylate (700 mg, 2.20 mmol, 1.0 eq.). The crude residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give methyl 4-(1- tert-butoxycarbonyl-3-piperidyl)pyridine-2-carboxylate enantiomer 1 (194 mg, 0.606 mmol). Step B: Preparation of methyl 4-(3-piperidyl)pyridine-2-carboxylate enantiomer 1 Methyl 4-(3-piperidyl)pyridine-2-carboxylate enantiomer 1 was prepared according to General Procedure 3A using methyl 4-(1-tert-butoxycarbonyl-3-piperidyl)pyridine-2- carboxylate enantiomer 1 (194 mg, 0.606 mmol, 1.0 eq.) and trifluoroacetic acid (464 µL, 6.06 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give methyl 4-(3-piperidyl)pyridine-2- carboxylate enantiomer 1 (133 mg, 0.604 mmol). Step C: Preparation of methyl 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 1 Oxetan-3-one (65.3 mg, 0.906 mmol, 1.5 eq.) and acetic acid (69.1 µL, 1.21 mmol, 2.0 eq.) were added to a methyl 4-(3-piperidyl)pyridine-2-carboxylate enantiomer 1 (133 mg, 0.604 mmol, 1.0 eq.) solution in THF (5 mL). The reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (384 mg, 1.81 mmol, 3.0 eq.) was added at 0 °C and the mixture was stirred at room temperature until completion of the reaction. The reaction mixture was concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 4-[1-(oxetan-3-yl)-3- piperidyl]pyridine-2-carboxylate enantiomer 1 (62.0 mg, 0.224 mmol). Step D: Preparation of lithium 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 1 Lithium 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 1 was prepared according to General Procedure 4B using methyl 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2- carboxylate enantiomer 1 (62.0 mg, 0.224 mmol, 1.0 eq.) to give lithium 4-[1-(oxetan-3-yl)-3- piperidyl]pyridine-2-carboxylate enantiomer 1 (60.0 mg, 0.224 mmol). The compound was engaged into the next step without further purification. (oxetan-3-yl)-3- 2- diastereomer 1 tert-Butyl N-[[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate diastereomer 1 was prepared according to General Procedure 6A using Intermediate 1 (90.0 mg, 0.228 mmol, 1.0 eq.) and lithium 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 1 (61.0 mg, 0.228 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[[4-[1- (oxetan-3-yl)-3-piperidyl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate diastereomer 1 (145 mg, 0.227 mmol). Step F: Preparation of Example 55 Example 55 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate diastereomer 1 (145 mg, 0.227 mmol, 1.0 eq.) and trifluoroacetic acid (174 µL, 2.27 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 55 (73.0 mg, 0.136 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (d, 1H), 8.57 (m, 1H), 7.93 (m, 1H), 7.84 (m, 1H), 7.71 (m, 1H), 7.54 (m, 1H), 7.5 (m, 2H), 7.44 (m, 1H), 7.36 (m, 2H), 5.24 (m, 1H), 4.49 (m, 4H), 3.67 (m, 2H), 3.43 (m, 1H), 2.9 (m, 1H), 2.74 (br d, 1H), 2.68 (m, 1H), 1.94 (m, 1H), 1.87 (m, 2H), 1.85 (m, 1H), 1.71 (m, 1H), 1.61 (m, 1H), 1.57 (m, 3H), 1.46 (m, 1H). [M+H]+=539.2616. Example 56: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxamide diastereomer 2 Step A: Preparation of methyl 4-(1-tert-butoxycarbonyl-3-piperidyl)pyridine-2-carboxylate enantiomer 2 Methyl 4-(1-tert-butoxycarbonyl-3-piperidyl)pyridine-2-carboxylate enantiomer 2 was prepared according to General Procedure 7B using methyl 4-(1-tert-butoxycarbonyl-3,6- dihydro-2H-pyridin-5-yl)pyridine-2-carboxylate (700 mg, 2.20 mmol, 1.0 eq.). The crude residues were purified by SFC (carbon dioxide / methanol / diethylamine) to give methyl 4-(1- tert-butoxycarbonyl-3-piperidyl)pyridine-2-carboxylate enantiomer 2 (185 mg, 0.577 mmol). Step B: Preparation of methyl 4-(3-piperidyl)pyridine-2-carboxylate enantiomer 2 Methyl 4-(3-piperidyl)pyridine-2-carboxylate was prepared according to General Procedure 3A using methyl 4-(1-tert-butoxycarbonyl-3-piperidyl)pyridine-2-carboxylate enantiomer 2 (185 mg, 0.577 mmol, 1.0 eq.) and trifluoroacetic acid (442 µL, 5.77 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give methyl 4-(3-piperidyl)pyridine-2-carboxylate enantiomer 2 (121 mg, 0.549 mmol). Step C: Preparation of methyl 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 2 Oxetan-3-one (59.4 mg, 0.824 mmol, 1.5 eq.) and acetic acid (62.9 µL, 1.10 mmol, 2.0 eq.) were added to a methyl 4-(3-piperidyl)pyridine-2-carboxylate enantiomer 2 (121 mg, 0.549 mmol, 1.0 eq.) solution in THF (5 mL). The reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (349 mg, 1.65 mmol, 3.0 eq.) was added at 0 °C and the mixture was stirred at room temperature until completion of the reaction. The reaction mixture was concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 4-[1-(oxetan-3-yl)-3- piperidyl]pyridine-2-carboxylate enantiomer 2 (126 mg, 0.456 mmol). Step D: Preparation of lithium 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 2 Lithium 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 2 was prepared according to General Procedure 4B using methyl 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2- carboxylate enantiomer 2 (126 mg, 0.456 mmol, 1.0 eq.) to give lithium 4-[1-(oxetan-3-yl)-3- piperidyl]pyridine-2-carboxylate enantiomer 2 (122 mg, 0.455 mmol). The compound was engaged into the next step without further purification. (oxetan-3-yl)-3- 2- diastereomer 2 tert-Butyl N-[[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate diastereomer 2 was prepared according to General Procedure 6A using Intermediate 1 (180 mg, 0.456 mmol, 1.0 eq.) and lithium 4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carboxylate enantiomer 2 (122 mg, 0.456 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[[4-[1- (oxetan-3-yl)-3-piperidyl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate diastereomer 2 (290 mg, 0.454 mmol). Step F: Preparation of Example 56 Example 56 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-[1-(oxetan-3-yl)-3-piperidyl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate enantiomer 2 (290 mg, 0.454 mmol, 1.0 eq.) and trifluoroacetic acid (348 µL, 4.54 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to Example 56 (57.0 mg, 0.106 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.07 (d, 1H), 8.57 (m, 1H), 7.93 (m, 1H), 7.84 (m, 1H), 7.71 (m, 1H), 7.54 (m, 1H), 7.5 (m, 2H), 7.44 (m, 1H), 7.36 (m, 2H), 5.24 (m, 1H), 4.49 (m, 4H), 3.67 (m, 2H), 3.43 (m, 1H), 2.9 (m, 1H), 2.74 (br d, 1H), 2.68 (m, 1H), 1.94 (m, 1H), 1.87 (m, 2H), 1.85 (m, 1H), 1.71 (m, 1H), 1.61 (m, 1H), 1.57 (m, 3H), 1.46 (m, 1H). [M+H]+=539.2612. Example 57: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(oxetan-3-yl)pyrrol-3-yl]pyridine-2-carboxamide Step A: Preparation of methyl 4-(1-tert-butoxycarbonyl-2,5-dihydropyrrol-3-yl)pyridine-2- carboxylate Methyl 4-(1-tert-butoxycarbonyl-2,5-dihydropyrrol-3-yl)pyridine-2-carboxylate was prepared according to General Procedure 2A using methyl 4-bromopyridine-2-carboxylate (1.00 g, 4.63 mmol, 1.0 eq.) and tert-butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,5- dihydropyrrole-1-carboxylate (1.64 g, 5.56 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 4-(1-tert- butoxycarbonyl-2,5-dihydropyrrol-3-yl)pyridine-2-carboxylate (1.12 g, 3.68 mmol). Step B: Preparation of methyl 4-(2,5-dihydro-1H-pyrrol-3-yl)pyridine-2-carboxylate Methyl 4-(2,5-dihydro-1H-pyrrol-3-yl)pyridine-2-carboxylate was prepared according to General Procedure 3A using methyl 4-(1-tert-butoxycarbonyl-2,5-dihydropyrrol-3- yl)pyridine-2-carboxylate (1.12 g, 3.68 mmol, 1.0 eq.) and trifluoroacetic acid (2.82 mL, 36.8 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give methyl 4-(2,5-dihydro-1H-pyrrol-3- yl)pyridine-2-carboxylate (733 mg, 3.59 mmol). 2- carboxylate Oxetan-3-one (132 mg, 1.83 mmol, 1.5 eq.) and acetic acid (140 µL, 2.45 mmol, 2.0 eq.) were added to a methyl 4-(2,5-dihydro-1H-pyrrol-3-yl)pyridine-2-carboxylate (250 mg, 1.22 mmol, 1.0 eq.) solution in THF (10 mL). The reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (778 mg, 12.4 mmol, 10.1 eq.) was added at 0 °C and the mixture was stirred at room temperature until completion of the reaction. The reaction mixture was concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 4-[1-(oxetan-3-yl)- 2,5-dihydropyrrol-3-yl]pyridine-2-carboxylate (134 mg, 0.515 mmol). Step D: Preparation of lithium 4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2- carboxylate Lithium 4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2-carboxylate was prepared according to General Procedure 4B using methyl 4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3- yl]pyridine-2-carboxylate (134 mg, 0.515 mmol, 1.0 eq.) to give lithium 4-[1-(oxetan-3-yl)- 2,5-dihydropyrrol-3-yl]pyridine-2-carboxylate (129 mg, 0.512 mmol). The compound was engaged into the next step without further purification. -1-[[4-[1-(oxetan-3-yl)-2,5- 3- tert-Butyl N-[[2-[4-[(1R)-1-[[4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to a modified General Procedure 6A using Intermediate 1 (200 mg, 0.507 mmol, 1.0 eq.), lithium 4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2-carboxylate (128 mg, 0.507 mmol, 1.0 eq.) and 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethylammonium tetrafluoroborate (212 mg, 0.659 mmol, 1.3 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1- [[4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (300 mg, 0.482 mmol). Step F: Preparation of Example 57 Example 57 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (300 mg, 0.482 mmol, 1.0 eq.) and trifluoroacetic acid (369 µL, 4.82 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 57 (38.0 mg, 0.0730 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.09 (m, 1H), 8.52 (d, 1H), 8.14 (d, 1H), 7.95 (t, 1H), 7.84 (d, 1H), 7.73 (m, 2H), 7.53 (d, 2H), 7.45 (d, 1H), 7.37 (d, 2H), 7.16 (t, 1H), 6.7 (dd, 1H), 5.34 (m, 2H), 4.94 (t, 2H), 4.83 (m, 2H), 3.68 (s, 2H), 1.9 (br d, 2H), 1.59 (d, 3H). [M+H]+=521.2136. -4- 2-carboxamide -tetrahydrofuran-3- 2-carboxylate Cesium carbonate (1.89 g, 5.80 mmol, 2.0 eq.) and methyl 4-chloropyrimidine-2-carboxylate (500 mg, 2.90 mmol, 1.0 eq.) were added to a (3R)-tetrahydrofuran-3-ol (766 mg, 8.69 mmol, 3.0 eq.) solution in DMF (10 mL) at 0 °C. The reaction mixture was warmed up to room temperature and stirred until completion of the reaction. The reaction media was concentrated under reduced pressure, taken in water and the organic layer was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 4-[(3R)-tetrahydrofuran-3- yl]oxypyrimidine-2-carboxylate (600 mg, 2.68 mmol). -tetrahydrofuran-3- 2-carboxylate Lithium 4-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-2-carboxylate was prepared according to General Procedure 4B using methyl 4-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-2- carboxylate (600 mg, 2.68 mmol, 1.0 eq.) to give lithium 4-[(3R)-tetrahydrofuran-3- yl]oxypyrimidine-2-carboxylate (578 mg, 2.67 mmol). The compound was engaged into the next step without further purification. Step C: Preparation of 4-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-2-carbonyl chloride Oxalyl chloride (2.10 mL, 5.35 mmol, 2.0 eq.) and DMF (20.7 mL, 0.267 mmol, 0.1 eq.) were added to a lithium 4-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-2-carboxylate (578 mg, 2.67 mmol, 1.0 eq.) solution in dichloromethane (5 mL) at 0 °C. The reaction mixture was warmed up to room temperature and stirred until completion of the reaction. The reaction media was concentrated to give the crude 4-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-2-carbonyl chloride (470 mg, 2.06 mmol). The compound was engaged into the next step without further purification. -1-[[4-[(3R)-tetrahydrofuran-3- tert-Butyl N-[[2-[4-[(1R)-1-[[4-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate N,N-Di-iso- propylethylamine (697 µL, 4.00 mmol, 3.0 eq.) and tert-butyl-N-[[2-[4-[(1R)-1- aminoethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate (526 mg, 1.33 mmol, 1.0 eq.) were added to a 4-[(3R)-tetrahydrofuran-3-yl]oxypyrimidine-2-carbonyl chloride (305 mg, 1.33 mmol, 1.0 eq.) solution in THF (10 mL) at 0 °C. The reaction mixture was stirred at room temperature until completion of the reaction. The reaction media was taken in water and the organic layer was extracted using dichloromethane, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[[4-[(3R)- tetrahydrofuran-3-yl]oxypyrimidine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (323 mg, 0.551 mmol). Step E: Preparation of Example 58 Example 58 was prepared according to General Procedure 3A using -[(1R)-1-[[4-[(3R)- tetrahydrofuran-3-yl]oxypyrimidine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (323 mg, 0.551 mmol, 1.0 eq.) and trifluoroacetic acid (422 µL, 5.51 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 58 (60.0 mg, 0.123 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.09 (d, 1H), 8.66 (d, 1H), 7.84 (d, 1H), 7.71 (d, 1H), 7.51 (d, 2H), 7.45 (m, 1H), 7.38 (d, 2H), 7.1 (d, 1H), 5.76 (td, 1H), 5.22 (quin, 1H), 3.86 (m, 4H), 3.68 (s, 2H), 2.29 (m, 1H), 2.09 (br s, 2H), 2.05 (m, 1H), 1.57 (d, 3H). [M+H]+ = 487.1947. Example 59: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- [1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2-carboxamide Example 59 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-[1-(oxetan-3-yl)-2,5-dihydropyrrol-3-yl]pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (300 mg, 0.482 mmol, 1.0 eq.) and trifluoroacetic acid (369 µL, 4.82 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 59 (58.0 mg, 0.111 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.12 (d, 1H), 8.63 (d, 1H), 7.95 (d, 1H), 7.84 (d, 1H), 7.71 (dd, 1H), 7.63 (dd, 1H), 7.52 (d, 2H), 7.44 (s, 1H), 7.36 (d, 2H), 6.81 (d, 1H), 5.25 (m, 1H), 4.58 (m, 4H), 3.98 (m, 1H), 3.88 (m, 2H), 3.67 (s, 4H), 2 (m, 2H), 1.58 (d, 3H). [M+H]+ = 522.2243. Example 60: 4-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyridine-2-carboxamide Step A: Preparation of tert-butyl N-[[2-[4-[(1R)-1-[[4-(4-acetylpiperazin-1-yl)pyridine-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate tert-Butyl N-[[2-[4-[(1R)-1-[[4-(4-acetylpiperazin-1-yl)pyridine-2- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 5 using Intermediate 4 (250 mg, 0.432 mmol, 1.0 eq.) and 1- piperazin-1-ylethanone (67.0 mg, 0.519 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4- [(1R)-1-[[4-(4-acetylpiperazin-1-yl)pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (62.0 mg, 0.0892 mmol). Step B: Preparation of Example 60 Example 60 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-(4-acetylpiperazin-1-yl)pyridine-2-carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl) phenyl]methyl]carbamate (62.0 mg, 0.0991 mmol, 1.0 eq.) and trifluoroacetic acid (76.0 µL, 0.991 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to Example 60 (26.0 mg, 0.0495 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.95 (d, 1H), 8.25 (d, 1H), 7.84 (d, 1H), 7.71 (dd, 1H), 7.5 (d, 2H), 7.44 (s, 2H), 7.36 (d, 2H), 7 (dd, 1H), 5.21 (m, 1H), 3.67 (s, 2H), 3.57 (br d, 4H), 3.43 (m, 4H), 2.04 (s, 3H), 1.97 (br m, 2H), 1.56 (d, 3H). [M+H]+=526.2398. -4- Step A: Preparation of tert-butyl N- (4-oxa-7-azaspiro[2.5]octan-7- yl)pyridine-2-carbonyl]amino] - phenyl]methyl]carbamate tert-Butyl N-[[2-[4-[(1R)-1-[[4-(4-oxa-7-azaspiro[2.5]octan-7-yl)pyridine-2-carbonyl]amino] ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 5 using Intermediate 4 (250 mg, 0.432 mmol, 1.0 eq.) and 4-oxa-7- azaspiro[2.5]octane.HCl (78.0 mg, 0.519 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4- [(1R)-1-[[4-(4-oxa-7-azaspiro[2.5]octan-7-yl)pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (346 mg, 0.510 mmol). Step B: Preparation of Example 61 Example 61 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[4-(4-oxa-7-azaspiro[2.5]octan-7-yl)pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (282 mg, 0.462 mmol, 1.0 eq.) and trifluoroacetic acid (354 µL, 4.62 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 61 (25.0 mg, 0.0490 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.94 (d, 1H), 8.24 (d, 1H), 7.84 (d, 1H), 7.71 (dd, 1H), 7.49 (d, 2H), 7.43 (m, 2H), 7.36 (d, 2H), 7 (dd, 1H), 5.21 (quin, 1H), 3.78 (m, 2H), 3.67 (s, 2H), 3.42 (m, 2H), 3.35 (s, 2H), 1.88 (br s, 2H), 1.56 (d, 3H), 0.7 (m, 4H). [M+H]+=511.2293. -2- Step A: Preparation of methyl 2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carboxylate Methyl 2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carboxylate was prepared according to General Procedure 2A using methyl 2-bromopyridine-4-carboxylate (800 mg, 3.70 mmol, 1.0 eq.) and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (1.05 g, 4.44 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carboxylate (418 mg, 1.71 mmol). Step B: Preparation of sodium 2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carboxylate Sodium 2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carboxylate was prepared according to a modified General Procedure 4A using methyl 2-(1-methyl-6-oxo-3-pyridyl)pyridine-4- carboxylate (697 mg, 1.71 mmol). After full conversion of starting material, the reaction media was freeze-dried to give the crude sodium 2-(1-methyl-6-oxo-3-pyridyl)pyridine-4- carboxylate (415 mg, 1.65 mmol). The compound was engaged into the next step without further purification. -1-[[2-(1-methyl-6-oxo-3- tert-Butyl N-[[2-[4-[(1R)-1-[[2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (650 mg, 1.65 mmol, 1.0 eq.) and sodium 2-(1-methyl-6- oxo-3-pyridyl)pyridine-4-carboxylate (416 mg, 1.65 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (ethyl acetate / ethanol) to give tert-butyl N-[[2- [4-[(1R)-1-[[2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (608 mg, 1.00 mmol). Step D: Preparation Example 62 Example 62 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[2-(1-methyl-6-oxo-3-pyridyl)pyridine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (308 mg, 0.508 mmol, 1.0 eq.) and trifluoroacetic acid (389 µL, 5.08 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 62 (50.0 mg, 0.0987 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.16 (d, 1H), 8.72 (d, 1H), 8.61 (d, 1H), 8.22 (dd, 1H), 8.17 (s, 1H), 7.85 (d, 1H), 7.72 (dd, 1H), 7.67 (dd, 1H), 7.51 (d, 2H), 7.45 (d, 1H), 7.39 (d, 2H), 6.54 (d, 1H), 5.28 (quin, 1H), 3.69 (s, 2H), 3.56 (s, 3H), 2.14 (br s, 2H), 1.57 (d, 3H). [M+H]+=507.2002. Example 63: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- (1-methyl-2-oxo-4-pyridyl)pyridine-3-carboxamide Step A: Preparation of methyl 5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carboxylate Methyl 5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carboxylate was prepared according to General Procedure 2A using methyl 5-bromopyridine-3-carboxylate (800 mg, 3.70 mmol, 1.0 eq.) and (1-methyl-2-oxo-4-pyridyl)boronic acid (680 mg, 4.44 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carboxylate (630 mg, 2.58 mmol). Step B: Preparation of sodium 5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carboxylate Sodium 5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carboxylate was prepared according to a modified General Procedure 4A using methyl 5-(1-methyl-2-oxo-4-pyridyl)pyridine-3- carboxylate (700 mg, 2.87 mmol, 1.0 eq.). After full conversion of starting material, the reaction media was freeze-dried to give the crude sodium 5-(1-methyl-2-oxo-4- pyridyl)pyridine-3-carboxylate (640 mg, 2.54 mmol). The compound was engaged into the next step without further purification. -1-[[5-(1-methyl-2-oxo-4- tert-Butyl N-[[2-[4-[(1R)-1-[[5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (1.00 g, 2.54 mmol, 1.0 eq.) and sodium 5-(1-methyl-2- oxo-4-pyridyl)pyridine-3-carboxylate (640 mg, 2.54 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (ethyl acetate / ethanol) to give tert-butyl N-[[2- [4-[(1R)-1-[[5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (630 mg, 1.04 mmol). Step D: Preparation of Example 63 Example 63 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[5-(1-methyl-2-oxo-4-pyridyl)pyridine-3-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl) phenyl]methyl]carbamate (630 mg, 1.04 mmol, 1.0 eq.) and trifluoroacetic acid (795 µL, 10.4 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 63 (179 mg, 0.353 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.16 (br d, 1H), 9.09 (br d, 2H), 8.58 (s, 1H), 7.86 (t, 2H), 7.72 (br d, 1H), 7.52 (d, 2H), 7.45 (s, 1H), 7.39 (d, 2H), 6.93 (s, 1H), 6.74 (d, 1H), 5.29 (quin, 1H), 3.69 (s, 2H), 3.48 (s, 3H), 1.58 (d, 3H). [M+H]+=507.2002. Example 64: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yloxy-pyrimidine-4-carboxamide Step A: Preparation of 2-tetrahydropyran-4-yloxypyrimidine-4-carboxylic acid Tetrahydropyran-4-ol (966 mg, 9.46 mmol, 3.0 eq.) was added to a suspension of sodium hydride (416 mg, 10.4 mmol, 3.3 eq.) in THF (25 mL). The reaction mixture was stirred at room temperature for 30 minutes and a 2-chloropyrimidine-4-carboxylic acid (500 mg, 3.15 mmol, 1.0 eq.) solution in THF (10 mL) was added. The reaction mixture was refluxed until completion of the reaction. The reaction media was cooled down to room temperature and a 1 M aqueous hydrogen chloride solution was added until pH 1. The mixture was poured into brine and the organic layer was extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated under reduced pressure to give the crude 2-tetrahydropyran-4- yloxypyrimidine-4-carboxylic acid (750 mg, 3.30 mmol). The compound was engaged into the next step without further purification. 4- tert-Butyl N-[[2-[4-[(1R)-1-[(2-tetrahydropyran-4-yloxypyrimidine-4-carbonyl)amino]ethyl] phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6B using Intermediate 1 (264 mg, 0.669 mmol, 1.0 eq.) and 2-tetrahydropyran-4- yloxypyrimidine-4-carboxylic acid (150 mg, 0.669 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (ethyl acetate) to give tert-butyl N-[[2-[4-[(1R)- 1-[(2-tetrahydropyran-4-yloxypyrimidine-4-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (210 mg, 0.350 mmol). Step C: Preparation of Example 64 Example 64 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[(2-tetrahydropyran-4-yloxypyrimidine-4-carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl) phenyl]methyl]carbamate (210 mg, 0.350 mmol, 1.0 eq.) and trifluoroacetic acid (2.00 mL, 26.1 mmol, 75 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 64 (128 mg, 0.256 mmol). 1H NMR (400 MHz, dmso-d6) δ ppm 9.16 (d, 1H), 8.82 (d, 1H), 7.84 (d, 1H), 7.72 (d, 1H), 7.59 (d, 1H), 7.51 (m, 2H), 7.45 (s, 1H), 7.38 (m, 2H), 5.3 (tt, 1H), 5.24 (m, 1H), 3.89 (dt, 2H), 3.68 (s, 2H), 3.52 (m, 2H), 2.22 (br s, 2H), 2.06 (m, 2H), 1.7 (m, 2H), 1.58 (d, 3H). [M+H]+=501.2110. -6- Step A: Preparation of methyl 6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carboxylate Methyl 6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carboxylate was prepared according to General Procedure 2A using methyl 6-bromopyridine-2-carboxylate (800 mg, 3.70 mmol, 1.0 eq.) and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (1.05 mg, 4.44 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carboxylate (507 mg, 2.08 mmol). Step B: Preparation of sodium 6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carboxylate Sodium 6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carboxylate was prepared according to General Procedure 4A using methyl 6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carboxylate (507 mg, 2.08 mmol, 1.0 eq.). After full conversion of starting material, the reaction media was freeze-dried to give the crude sodium 6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carboxylate (510 mg, 2.02 mmol). The compound was engaged into the next step without further purification. Step C: Preparation of tert-butyl N- (1-methyl-6-oxo-3-pyridyl)pyridine-2- carbonyl]amino]ethyl]phenyl]-4- methyl]carbamate tert-Butyl N-[[2-[4-[(1R)-1-[[6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (1.00 g, 2.54 mmol, 1.0 eq.) and sodium 6-(1-methyl-6- oxo-3-pyridyl)pyridine-2-carboxylate (640 mg, 2.54 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (ethyl acetate / ethanol) to give tert-butyl N-[[2- [4-[(1R)-1-[[6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (404 mg, 0.666 mmol). Step D: Preparation of Example 65 Example 65 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[6-(1-methyl-6-oxo-3-pyridyl)pyridine-2-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (204 mg, 0.336 mmol, 1.0 eq.) and trifluoroacetic acid (258 µL, 3.36 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 65 (109 mg, 0.215 mmol).1H NMR (500 MHz, dmso-d6) δ ppm 9.08 (d, 1H), 8.76 (d, 1H), 8.49 (dd, 1H), 8.02 (m, 1H), 8.02 (m, 1H), 7.9 (m, 1H), 7.84 (d, 1H), 7.72 (dd, 1H), 7.54 (d, 2H), 7.45 (d, 1H), 7.39 (m, 2H), 6.54 (d, 1H), 5.33 (quin, 1H), 3.7 (s, 2H), 3.57 (s, 3H), 2.72 (br s, 2H), 1.65 (d, 3H). [M+H]+=507.2003. Example 66: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- (1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxamide Step A: Preparation of methyl 5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxylate Methyl 5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxylate was prepared according to General Procedure 2A using methyl 5-bromopyridine-3-carboxylate (800 mg, 3.70 mmol, 1.0 eq.) and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (1.05 g, 4.44 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxylate (400 mg, 1.64 mmol). Step B: Preparation of sodium;5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxylate Sodium 5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxylate was prepared according to General Procedure 4A using methyl 5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxylate (400 mg, 1.64 mmol, 1.0 eq.). After full conversion of starting material, the reaction media was freeze-dried to give the crude sodium 5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carboxylate (400 mg, 1.59 mmol). The compound was engaged into the next step without further purification. -1-[[5-(1-methyl-6-oxo-3- tert-Butyl N-[[2-[4-[(1R)-1-[[5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carbonyl]amino]ethyl] phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (620 mg, 1.57 mmol, 1.0 eq.) and sodium 5-(1-methyl-6- oxo-3-pyridyl)pyridine-3-carboxylate (397 mg, 1.57 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (ethyl acetate / ethanol) to give tert-butyl N-[[2- [4-[(1R)-1-[[5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (215 mg, 0.355 mmol). Step D: Preparation of Example 66 Example 66 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[5-(1-methyl-6-oxo-3-pyridyl)pyridine-3-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl) phenyl]methyl]carbamate (215 mg, 0.473 mmol, 1.0 eq.) and trifluoroacetic acid (362 µL, 4.73 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (methanol / water / ammonium bicarbonate) to give Example 66 (60.0 mg, 0.119 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 9.09 (d, 1H), 8.96 (d, 2H), 8.4 (s, 1H), 8.34 (d, 1H), 7.96 (dd, 1H), 7.85 (d, 1H), 7.71 (dd, 1H), 7.51 (d, 2H), 7.44 (d, 1H), 7.39 (d, 2H), 6.55 (d, 1H), 5.29 (quin, 1H), 3.68 (s, 2H), 3.53 (s, 3H), 1.89 (br s, 2H), 1.57 (d, 3H). [M+H]+=507.2006. -2- Step A: Preparation of methyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)pyrimidine-4- carboxylate Methyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)pyrimidine-4-carboxylate was prepared according to General Procedure 5 using methyl 2-bromopyrimidine-4-carboxylate (1.00 g, 4.61 mmol, 1.0 eq.) and tert-butyl piperazine-1-carboxylate (1.03 g, 5.53 mmol, 1.2 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give methyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)pyrimidine-4-carboxylate (1.38 g, 3.85 mmol). Step B: Preparation of methyl 2-piperazin-1-ylpyrimidine-4-carboxylate Methyl 2-piperazin-1-ylpyrimidine-4-carboxylate was prepared according to General Procedure 3A using methyl 2-(4-tert-butoxycarbonylpiperazin-1-yl)pyrimidine-4-carboxylate (500 mg, 1.55 mmol, 1.0 eq.) and trifluoroacetic acid (1.19 mL, 15.5 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give methyl 2-piperazin-1-ylpyrimidine-4-carboxylate (127 mg, 0.572 mmol). Step C: Preparation of methyl 2-[4-(oxetan-3-ylmethyl)piperazin-1-yl]pyrimidine-4- carboxylate Potassium carbonate (157 mg, 1.13 mmol, 0.9 eq.) and 3-(bromomethyl)oxetane (209 mg, 1.39 mmol, 1.1 eq.) were added to a methyl 2-piperazin-1-ylpyrimidine-4-carboxylate (280 mg, 1.26 mmol, 1.0 eq.) solution in acetonitrile (5 mL). The resulting mixture was refluxed until completion of the reaction. The reaction media was concentrated under reduced pressure. The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give methyl 2-[4-(oxetan-3-ylmethyl)piperazin-1- yl]pyrimidine-4-carboxylate (206 mg, 0.705 mmol). Step D: Preparation of lithium 2-[4-(oxetan-3-ylmethyl)piperazin-1-yl]pyrimidine-4- carboxylate Lithium 2-[4-(oxetan-3-ylmethyl)piperazin-1-yl]pyrimidine-4-carboxylate was prepared according to General Procedure 4B using methyl 2-[4-(oxetan-3-ylmethyl)piperazin-1- yl]pyrimidine-4-carboxylate (206 mg, 0.705 mmol, 1.0 eq.) to give lithium 2-[4-(oxetan-3- ylmethyl)piperazin-1-yl]pyrimidine-4-carboxylate (200 mg, 0.704 mmol). The compound was engaged into the next step without further purification. 1- tert-Butyl N-[[2-[4-[(1R)-1-[[2-[4-(oxetan-3-ylmethyl)piperazin-1-yl]pyrimidine-4- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6A using Intermediate 1 (270 mg, 0.685 mmol, 1.0 eq.) and lithium 2-[4-(oxetan-3-ylmethyl)piperazin-1-yl]pyrimidine-4-carboxylate (195 mg, 0.685 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / methanol) to give tert-butyl N-[[2-[4-[(1R)-1-[[2-[4-(oxetan-3- ylmethyl)piperazin-1-yl]pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (410 mg, 0.626 mmol). Step F: Preparation of Example 67 Example 67 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[2-[4-(oxetan-3-ylmethyl)piperazin-1-yl]pyrimidine-4-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (410 mg, 0.626 mmol, 1.0 eq.) and trifluoroacetic acid (480 µL, 6.26 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX. The crude residues were purified by reverse phase chromatography (acetonitrile / water / ammonium bicarbonate) to give Example 67 (60.0 mg, 0.108 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.93 (d, 1H), 8.56 (d, 1H), 7.84 (d, 1H), 7.71 (d, 1H), 7.49 (d, 2H), 7.44 (s, 1H), 7.38 (d, 2H), 7.1 (d, 1H), 5.25 (quin, 1H), 4.66 (dd, 2H), 4.28 (t, 2H), 3.82 (br s, 4H), 3.67 (s, 2H), 3.23 (m, 1H), 2.68 (d, 2H), 2.41 (m, 4H), 1.98 (br s, 2H), 1.59 (d, 3H). [M+H]+ = 555.2695. Example 68: N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- [(2S,6S)-2,6-dimethylmorpholin-4-yl]pyridine-3-carboxamide Step A: Preparation of sodium 5-bromopyridine-3-carboxylate Sodium 5-bromopyridine-3-carboxylate was prepared according to General Procedure 4A using methyl 5-bromopyridine-3-carboxylate (800 mg, 3.70 mmol, 1.0 eq.). After full conversion of starting material, the reaction media was freeze-dried to give the crude sodium 5-bromopyridine-3-carboxylate (800 mg, 3.57 mmol). The compound was engaged into the next step without further purification. Step B: Preparation of tert-butyl N- [4-[(1R)-1-[(5-bromopyridine-3- carbonyl)amino]ethyl]phenyl]-4- phenyl]methyl]carbamate tert-Butyl N-[[2-[4-[(1R)-1-[(5-bromopyridine-3-carbonyl)amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate was prepared according to General Procedure 6B using Intermediate 1 (1.23 g, 3.13 mmol, 1.0 eq.) and sodium 5-bromopyridine-3-carboxylate (700 mg, 3.13 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (dichloromethane / ethyl acetate) to give tert-butyl N-[[2-[4-[(1R)-1-[(5- bromopyridine-3-carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate (1.12 g, 1.94 mmol). tert-Butyl N-[[2-[4-[(1S)-1-[[5-[(2S,6S)-2,6-dimethylmorpholin-4-yl]pyridine-3-carbonyl] amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate was prepared according to a modified General Procedure 5 using tert-butyl N-[[2-[4-[(1R)-1-[(5-bromopyridine-3- carbonyl)amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate (150 mg, 0.259 mmol, 1.0 eq.) and (2S,6S)-2,6-dimethylmorpholine (30.0 mg, 0.259 mmol, 1.0 eq.). The crude residues were purified by silica gel column chromatography (heptane / ethyl acetate) to give tert-butyl N-[[2-[4-[(1R)-1-[[5-[(2S,6S)-2,6-dimethylmorpholin-4-yl]pyridine-3- carbonyl]amino]ethyl]phenyl]-4-(trifluoromethyl)phenyl]methyl]carbamate (37.0 mg, 0.0604 mmol). Step D: Preparation of Example 68 Example 68 was prepared according to General Procedure 3A using tert-butyl N-[[2-[4-[(1R)- 1-[[5-[(2S,6S)-2,6-dimethylmorpholin-4-yl]pyridine-3-carbonyl]amino]ethyl]phenyl]-4- (trifluoromethyl)phenyl]methyl]carbamate (37.0 mg, 0.0604 mmol, 1.0 eq.) and trifluoroacetic acid (46.0 µL, 0.604 mmol, 10 eq.). After completion of the reaction, methanol was added and the reaction mixture was eluted through a PoraPak Rxn CX to give Example 68 (23.0 mg, 0.0449 mmol).1H NMR (400 MHz, dmso-d6) δ ppm 8.96 (d, 1H), 8.48 (s, 1H), 8.42 (d, 1H), 7.83 (s, 1H), 7.73 (dd, 1H), 7.65 (m, 1H), 7.49 (d, 2H), 7.46 (d, 1H), 7.38 (d, 2H), 5.26 (quin, 1H), 4.09 (m, 2H), 3.71 (s, 2H), 3.33 (br d, 2H), 2.97 (dd, 2H), 2.76 (m, 1H), 1.55 (d, 3H), 1.22 (d, 6H). [M+H]+ = 513.2473. 1-[4-[2-(aminomethyl)-5- 4-carboxamide Step A: Preparation of methyl 6-(4-acetylpiperazin-1-yl)pyrimidine-4-carboxylate A 1-Piperazin-1-ylethanone (743 mg, 5.80 mmol, 1.0 eq.) solution in dichloromethane (10 mL) was added to a methyl 6-chloropyrimidine-4-carboxylate (1.00 g, 5.80 mmol, 1.0 eq.) solution in dichloromethane (10 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 30 min and warmed up to room temperature overnight. The reaction mixture was diluted with water and the organic layer was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to give the crude methyl 6-(4-acetylpiperazin-1-yl)pyrimidine-4-carboxylate (1.60 g, 6.10 mmol). The compound was engaged into the next step without further purification. Step B: Preparation...

Claims

CLAIMS 1. Compound of Formula (I):  wherein: ^ Cy1represents an aryl group, a heterocycloalkyl group, or a heteroaryl group, ^ R1 represents a halogen atom, a linear or branched (C1-C6)alkyl group, or a linear or branched halo(C1-C6)alkyl group, ^ R2 represents a linear or branched amino(C1-C6)alkyl group, a linear or branched (C1-C6)alkylamino(C1-C6)alkyl group, a heterocycloalkyl group, a heterocycloalkylalkyl group, or a -CH(CH2-OH)-NH2group, ^ R3 represents a hydrogen atom, a halogen atom, or a linear or branched (C1-C6)alkyl group, ^ R4represents a hydrogen atom or a halogen atom, ^ R5 represents a hydrogen atom, a linear or branched (C1-C6)alkoxy group, or  ^ R6 represents a hydrogen atom, a halogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, a halo(C1-C6)alkoxy group, a linear or branched (C1-C6)alkylsulfonyl group, a linear or branched di(C1-C6)alkylphosphoryl group, a cycloalkyl group, or a heterocycloalkyl group, ^ X represents a -C(R9)- group or a nitrogen atom, ^ R9 represents a hydrogen atom,or the substituents of the pair (R2,R9) form together with the carbon atoms carrying them a non-aromatic 5-membered ring which may contain a nitrogen atom, it being understood that resulting ring may be substituted by from 1 to 2 groups selected from an amino group, a linear or branched (C1-C6)alkylamino group and a linear or branched (C1-C6)alkyl, ^ W represents a bond, an oxygen atom, a -SO2- group, or a linear or branched hydroxy(C1-C6)alkylene group, ^ Cy2 represents a cycloalkyl group, a heterocycloalkyl group, or a heteroaryl group, ^ R7represents a hydrogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched halo(C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, an acetyl group, a propionyl group, an isobutyryl group, a cycloalkyl group, a cycloalkylalkyl group, a heterocycloalkyl group,^ R8 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group,their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base.

2. Compound of Formula (I) according to claim 1:  wherein: ^ Cy1 represents an aryl group or a heteroaryl group, ^ R1represents a halogen atom, a linear or branched (C1-C6)alkyl group, or a linear or branched halo(C1-C6)alkyl group, ^ R2 represents a linear or branched amino(C1-C6)alkyl group, a linear or branched (C1-C6)alkylamino(C1-C6)alkyl group, a heterocycloalkyl group, or a heterocycloalkylalkyl group, ^ R3 represents a hydrogen atom, a halogen atom, or a linear or branched (C1-C6)alkyl group, ^ R4 represents a hydrogen atom or a halogen atom, ^ R5represents a hydrogen atom, a linear or branched (C1-C6)alkoxy group, or  ^ R6represents a hydrogen atom, a halogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, a linear or branched (C1-C6)alkylsulfonyl group, a linear or branched di(C1-C6)alkylphosphoryl group, a cycloalkyl group, or a heterocycloalkyl group, ^ X represents a -C(R9)- group or a nitrogen atom,^ R9represents a hydrogen atom, or the substituents of the pair (R2,R9) form together with the carbon atoms carrying them a non-aromatic 5-membered ring which may contain a nitrogen atom, it being understood that resulting ring may be substituted by from 1 to 2 groups selected from an amino group, a linear or branched (C1-C6)alkylamino group and a linear or branched (C1-C6)alkyl, ^ W represents a bond, an oxygen atom, or a linear or branched hydroxy(C1-C6)alkylene group, ^ Cy2represents a cycloalkyl group, a heterocycloalkyl group, or a heteroaryl group, ^ R7represents a hydrogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched halo(C1-C6)alkyl group, an acetyl group, a cycloalkyl group, a heterocycloalkyl group,^ R8 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base.

3. Compound of Formula (I) according to claim 1: wherein: ^ Cy1 represents an aryl group or a heteroaryl group, ^ R1represents a halogen atom, a linear or branched (C1-C6)alkyl group, or a linear or branched halo(C1-C6)alkyl group, ^ R2 represents a linear or branched amino(C1-C6)alkyl group, a linear or branched (C1-C6)alkylamino(C1-C6)alkyl group, a heterocycloalkyl group, , ^ R3 represents a hydrogen atom, a halogen atom, or a linear or branched (C1-C6)alkyl group, ^ R4represents a hydrogen atom or a halogen atom, ^ R5 represents a hydrogen atom, a linear or branched (C1-C6)alkoxy group, or  ^ R6 represents a hydrogen atom, a halogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched (C1-C6)alkoxy group, a linear or branched (C1-C6)alkylsulfonyl group, a linear or branched di(C1-C6)alkylphosphoryl group, a cycloalkyl group, or a heterocycloalkyl group, ^ X represents a -C(R9)- group or a nitrogen atom, ^ R9 represents a hydrogen atom, or the substituents of the pair (R2,R9) form together with the carbon atoms carrying them a non-aromatic 5-membered ring which may contain a nitrogen atom, it being understood that resulting ring may be substituted by from 1 to 2 groups selected from an amino group, a linear or branched (C1-C6)alkylamino group and a linear or branched(C1-C6)alkyl, ^ W represents a bond, an oxygen atom, or a linear or branched hydroxy(C1-C6)alkylene group, ^ Cy2represents a cycloalkyl group, a heterocycloalkyl group, or a heteroaryl group, ^ R7 represents a hydrogen atom, a linear or branched (C1-C6)alkyl group, a linear or branched halo(C1-C6)alkyl group, an acetyl group, a cycloalkyl group, a heterocycloalkyl group,^ R8 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, their enantiomers and diastereoisomers, and addition salts thereof with a pharmaceutically acceptable acid or base.

4. Compound according to claim 1, which is a compound of Formula (I-a):  wherein R1, R2, R3, R4, R5, R6, Cy1 and X are as defined in claim 1.

5. Compound according to claim 1, which is a compound of Formula (I-b):  wherein R1, R2, R3, R4, R5, R6, Cy1and X are as defined in claim 1.

6. Compound according to claim 1, which is a compound of Formula (I-d):wherein R1, R2, R3, R4, R6, R7, R8, Cy1, Cy2, W and X are as defined in claim 1.

7. Compound according to claim 1, which is a compound of Formula (I-f):  wherein R1, R2, R3, R4, R6, R7, R8, Cy1, Cy2and X are as defined in claim 1.

8. Compound according to claim 1, which is a compound of Formula (I-h):wherein R4, R5, R6 and Cy1 are as defined for Formula (I).

9. Compound according to claim 1, which is a compound of Formula (I-j):wherein R4, R6, R7, R8, Cy1, Cy2 and W are as defined for Formula (I).

10. Compound according to claim 1, which is a compound of Formula (I-l):wherein R4, R6, R7, R8, Cy1and Cy2are as defined for Formula (I).

11. Compound according to claim 1, wherein Cy1represents a phenyl group, a thienyl group, a pyridinyl group, a pyridinyl-N-oxide group, a N-methylpyridiniumyl group, a pyrimidinyl group, a pyrimidinonyl group, a pyrazinyl group, a thiazolyl group, an oxazolyl group, an isoxazolyl group, a 1,3,4-oxadiazolyl group, a 1,2,4-oxadiazolyl group, a 1,3,4-thiadiazolyl group, a 1,4,5,6-tetrahydropyrimidinyl group, a pyridazinyl group, an indolinyl group, a triazinyl group, or a dihydro-1,4-benzoxazinyl group.

12. Compound according to claim 1, wherein Cy1represents a phenyl group, a thienyl group, a pyridinyl group, a pyridinyl-N-oxide group, a N-methylpyridiniumyl group, a pyrimidinyl group, a pyrazinyl group, a thiazolyl group, a pyridazinyl group, an indolinyl group, a triazinyl group, or a dihydro-1,4-benzoxazinyl group.

13. Compound according to claim 1, wherein Cy1 represents a pyridinyl group or a pyrimidinyl group.

14. Compound according to claim 1, wherein R1 represents a chlorine atom, a fluorine atom, a methyl group, a -CF3 group, or a -CHF2 group.

15. Compound according to claim 1, wherein R1 represents a chlorine atom, a methyl group, a -CF3 group, or a -CHF2 group.

16. Compound according to claim 1, wherein R1 represents a -CF3 group.

17. Compound according to claim 1, wherein R2represents a -CH2-NH2group, a -CH2-NH-CH3group, a -CH(CH3)-NH2group, a -CH(CH2-OH)-NH2group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azaspiro[3.3]heptanyl group, agroup,18. Compound according to claim 1, wherein R2represents a -CH2-NH2group, a -CH2-NH-CH3 group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azaspiro[3.3]heptanyl group,19. Compound according to claim 1, wherein R2represents a -CH2-NH2group, a -CH2-NH-CH3 group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, or an azaspiro[3.3]heptanyl group.

20. Compound according to claim 1, wherein R2 represents a -CH2-NH2 group.

21. Compound according to claim 1, wherein R3represents a hydrogen atom, a chlorine atom, a fluorine atom, or a methyl group.

22. Compound according to claim 1, wherein R3represents a hydrogen atom.

23. Compound according to claim 1, wherein R4 represents a hydrogen atom, a fluorine atom, or a chlorine atom.

24. Compound according to claim 1, wherein R4 represents a hydrogen atom.

25. Compound according to claim 1, wherein R5represents a hydrogen group, a methoxygroup, or  wherein W, Cy2, R7and R8are as defined in claim 1.

26. Compound according to claim 1, wherein R6 represents a hydrogen atom, a chlorine atom, a methyl group, a methoxy group, a -O-CHF2 group, a -SO2-CH2-CH3 group, a -P(=O)-(CH2-CH3)2group, a cyclopropyl group, or an oxetanyl group.

27. Compound according to claim 1, wherein R6 represents a hydrogen atom, a chlorine atom, a methyl group, a methoxy group, a -SO2-CH2-CH3group, a -P(=O)(CH2-CH3)2group, a cyclopropyl group, or an oxetanyl group.

28. Compound according to claim 1, wherein R6represents a hydrogen atom.

29. Compound according to claim 1, wherein X represents a -C(R9)- group.

30. Compound according to claim 1, wherein W represents a bond, an oxygen atom, a -SO2- group, or a -CH(OH)- group.

31. Compound according to claim 1, wherein W represents a bond, an oxygen atom, or a -CH(OH)- group.

32. Compound according to claim 1, wherein W represents a bond.

33. Compound according to claim 1, wherein Cy2 represents a heterocycloalkyl group or a heteroaryl group.

34. Compound according to claim 1, wherein Cy2 represents a cyclopropyl group, a tetrahydrofuranyl group, a pyrrolidinyl group, a morpholinyl group, a piperidinyl group, apiperazinyl group, a tetrahydropyranyl group, a dihydropyranyl group, a tetrahydropyridinyl group, a thiazolyl group, a 1,3,4-thiadiazolyl group, an oxazaspiro[3.3]heptanyl group, an oxazaspiro[2.5]octanyl group, an azabicyclo[3.1.0]hexanyl group, an oxaspiro[2.5]octanyl group, a pyrazolyl group, an imidazolyl group, a triazolyl group, an oxazaspiro[4.5]decanyl group, a 6,7-dihydro-4H- pyrazolo[1,5-a]pyrazinyl group, a diazaspiro[3.5]nonanyl group, an azasilinanyl group, an oxazaspiro[4.4]nonanyl group, a 5,6-dihydro-1,2,4-triazinyl group, a pyridonyl group, a dihydropyrrolyl group, a pyrrolyl group, a pyrimidinyl group, an oxazaspiro[3.4]octanyl group, an oxaphosphinanonyl group, a pyridinyl group, a pyridinyl-N-oxide group, a tetrahydrotriazinyl group, 2,2,3,3,5,5,6,6-octadeuteriopiperazin-1-yl, 2,2,6,6-tetradeuterio- 3H-pyran-4-yl, or a diazaspiro[3.3]heptanyl group.

35. Compound according to claim 1, wherein Cy2 represents a cyclopropyl group, a tetrahydrofuranyl group, a pyrrolidinyl group, a morpholinyl group, a piperidinyl group, a piperazinyl group, a tetrahydropyranyl group, a dihydropyranyl group, a tetrahydropyridinyl group, a thiazolyl group, an oxazaspiro[3.3]heptanyl group, an oxazaspiro[2.5]octanyl group, an azabicyclo[3.1.0]hexanyl group, an oxaspiro[2.5]octanyl group, a pyrazolyl group, an imidazolyl group, a pyridonyl group, a dihydropyrrolyl group, a pyrrolyl group, a pyrimidinyl group, an oxazaspiro[3.4]octanyl group, an oxaphosphinanonyl group, a pyridinyl group, a pyridinyl-N-oxide group, a tetrahydrotriazinyl group, or a diazaspiro[3.3]heptanyl group.

36. Compound according to claim 1, wherein Cy2 represents a morpholinyl group, a piperazinyl group, or a dihydropyranyl group.

37. Compound according to claim 1, wherein Cy2 represents a piperazinyl group.

38. Compound according to claim 1, wherein R7represents a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a methoxy group, an ethoxy group, an isopropyl group, a -CH2F group, a -CHF2 group, a -CF3 group, an acetyl group, a propionyl group, an isobutyryl group, a cyclopropyl group, a -CH2-cyclopropyl group, an oxetanyl group, a morpholinyl group, a tetrahydropyranyl group,39. Compound according to claim 1, wherein R7represents a hydrogen atom, a methyl group, an isopropyl group, a -CH2F group, a -CHF2 group, a -CF3 group, an acetyl group, a cyclopropyl group, an oxetanyl group, a morpholinyl group, a tetrahydropyranyl group,40. Compound according to claim 1, wherein R7 represents a hydrogen atom, or group.

41. Compound according to claim 1, wherein R8represents a hydrogen atom or a methyl group.

42. Compound according to claim 1, wherein R9represents a hydrogen atom.

43. Compounds according to claim 1, which are: - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5-(3,6- dihydro-2H-pyran-4-yl)nicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-isonicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5-[(3S)- tetrahydrofuran-3-yl]oxy-nicotinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-[(3R)- tetrahydrofuran-3-yl]oxy-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[4- (cyclopropanecarbonyl)piperazino]picolinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- tetrahydropyran-4-yl-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- tetrahydropyran-4-yl-pyrazinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4- morpholino-picolinamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6- morpholino-pyrazine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[(3R)- tetrahydrofuran-3-yl]oxy-pyrimidine-2-carboxamide;- 4-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyridine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yloxy-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-[4-(oxetan- 3-ylmethyl)piperazin-1-yl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-(2-oxa-7- azaspiro[3.4]octan-7-yl)pyridine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6-[4- (cyclopropanecarbonyl)piperazin-1-yl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(2-oxa-7- azaspiro[3.4]octan-7-yl)pyrimidine-4-carboxamide; - 2-(oxan-4-yl)-N-[(1R)-1-[4-[2-pyrrolidin-2-yl-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyrimidine-4-carboxamide; - 2-(4-acetylpiperazin-1-yl)-N-[(1R)-1-[4-[2-(aminomethyl)-5- (trifluoromethyl)phenyl]phenyl]ethyl]pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-5- tetrahydropyran-4-yl-1,3,4-oxadiazole-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-6-(3- methyltriazol-4-yl)pyrazine-2-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- tetrahydropyran-4-yl-oxazole-5-carboxamide.

44. Compounds according to claim 1, which are: - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2- morpholino-pyrimidine-4-carboxamide; - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-2-(3,6- dihydro-2H-pyran-4-yl)pyrimidine-4-carboxamide; or - N-[(1R)-1-[4-[2-(aminomethyl)-5-(trifluoromethyl)phenyl]phenyl]ethyl]-4-[4- (cyclopropanecarbonyl)piperazino]picolinamide.

45. A compound of Formula (V):wherein R1, R2, R3, R4 and X are as defined in in claim 1, for use as synthesis intermediate for the preparation of compounds of Formula (I) according to claim 1.

46. Compound of formula (V) according to claim 45, which is 1-[4-[5-(aminomethyl)-2- (trifluoromethyl)phenyl]phenyl]ethanamine.

47. Pharmaceutical composition comprising a compound of Formula (I) according to any one of claims 1 to 44 or an addition salt thereof with a pharmaceutically acceptable acid or base in combination with one or more pharmaceutically acceptable excipients.

48. Pharmaceutical composition according to claim 47 for use as SOS1 inhibitors.

49. Pharmaceutical composition according to claim 48 for use in the treatment of cancer, autoimmune diseases, diseases of immune system and genetic diseases.

50. Pharmaceutical composition according to claim 49 wherein cancer is selected from pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular cancer, breast cancer, ovarian cancer, prostate cancer, glioblastoma, renal cancer, sarcomas, glioma and malignant peripheral nerve sheath tumors.

51. Pharmaceutical composition according to claim 50 wherein genetic disease is selected from neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lengitines,capillary malformation-arteriovenous malformation syndrome, Costello syndrome, cardiofaciocutaneous syndrome, Legius syndrome and hereditary gingival fibromatosis.

52. Compound of Formula (I) according to any one of claims 1 to 44, or an addition salt thereof with a pharmaceutically acceptable acid or base, for use as SOS1 inhibitor.

53. Compound of Formula (I) according to any one of claims 1 to 44, or an addition salt thereof with a pharmaceutically acceptable acid or base, for use in the treatment of pancreatic cancer, lung cancer, colorectal cancer, cholangiocarcinoma, multiple myeloma, melanoma, uterine cancer, endometrial cancer, thyroid cancer, acute myeloid leukemia, bladder cancer, urothelial cancer, gastric cancer, cervical cancer, head and neck squamous cell carcinoma, diffuse large B cell lymphoma, esophageal cancer, chronic lymphocytic leukemia, hepatocellular cancer, breast cancer, ovarian cancer, prostate cancer, glioblastoma, renal cancer, sarcomas, glioma, malignant peripheral nerve sheath tumors, neurofibromatosis type 1, Noonan syndrome, Noonan syndrome with multiple lengitines, capillary malformation-arteriovenous malformation syndrome, Costello syndrome, cardiofaciocutaneous syndrome, Legius syndrome and hereditary gingival fibromatosis.

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