Further substituted imidazoles as inhibitors of nav1.8

Abstract

The invention relates to compounds according to general formula (I) which act as inhibitors of NaV1.8 and can be used in the treatment of pain.

Description

[0001] Further substituted imidazoles as inhibitors of Navl.8

[0002] The invention relates to compounds according to general formula (I) which act as inhibitors of Navi .8 and can be used in the treatment of pain.

[0003] Normal pain sensation (nociception) serves primarily as a survival mechanism, the body’s way of self-protection, alerting against (further) tissue damage and disease from noxious stimuli. For instance, acute pain can arise when the external environment (temperature, pressure, chemicals) activates modality specific receptors (nociceptors) and ion channels within the skin. The peripheral terminals of pain-signaling neurons - whose cell bodies are found in the dorsal root ganglia [DRG] and trigeminal ganglia [TG] - convert the external stimuli into electrochemical generator potentials. Specific voltage-gated sodium channels (Navs) integrate and amplify these generator signals until the threshold for an action potential [AP] is reached. Thus, what starts as a noxious stimuli in the periphery eventually leads to action potential firing that travels towards the central nervous system, synapsing first onto neurons in the spinal cord and then towards the brain. Navs also function to support propagation of action potentials to the central terminals within the spinal cord. At the end of its travels along the somatosensory pathway, the action potential signal is interpreted as pain by the brain (Lumpkin and Caterina, Nature (2007), Vol.445 pp 858-865; and Crawford and Caterina Toxicologic Pathology (2020) 48(1)-174; Goodwin G and McMahon S.B. Nature Reviews Neuroscience (2021) Vol 22 pp 263-274; Bennett D.L. et al. Physiol Rev 99 (2019) Vol 99 pp 1079-1151).

[0004] Abnormal persistent neuropathic pain arises as a consequence of a lesion or disease of this somatosensory pathway. In response to nerve injury or inflammation, abnormal changes in ion channel expression can cause hyper-excitability of pain-signaling neurons and their nerves / axons, thus resulting in pathological pain.

[0005] The voltage-gated Navi.8 sodium channel is a therapeutic target for analgesia because of its restricted expression profile (almost exclusive to peripheral sensory tissues), its placement along the pain pathway (free nerve endings, sciatic nerve, and DRG), prominent physiological role in pain signaling (supports upstroke of AP and facilitates repetitive AP firing), and supporting genetic / pharmaco-phenotypic evidence (human / animal studies showing changes in Navi.8 function cause parallel changes in pain sensitivity).

[0006] Regarding its expression profile along the pain pathway, because Navi .8 was first found predominantly in peripheral sensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG), it was originally termed SNS (sensory neuron specific) (Akopian A.N. et al Nature (1996) Vol 379 pp 257-261) or PN3 (peripheral nerve 3) (Sangameswaran L. et al J. Biol. Chem. (1996) Vol 271 pp 5953-5956). As well, Navi.8 is localized at free nerve endings, where pain signaling is initiated in the skin (Persson A.K. et al Mol. Pain. (2010) 6:84) and is diffusely localized along the entire length of non-myelinated axons of sciatic nerve (Rush A.M. et al. Eur. J.Neurosci (2005) Vol 22 pp 39-49).

[0007] In contrast, Nav1.8 has minimal expression in nonneuronal tissue, such as heart and skeletal muscle, and in the CNS, including brain and spinal cord (9, 10, 338, 406) (Akopian A.N. op. cit. ; Akopian A.N. et al. Nat. Neurosci (1999) Vol 2 pp 541-548; Novakovic S.D. et al. J. Neurosci. (1998) Vol 18, pp 2174-2187; and Sagameswaran L. op. cit.).

[0008] Regarding its physiological role, Navi.8 contributes the majority of the inward current during the rising phase of an all-or-none action potential in nociceptive sensory neurons (Blair N.T. et al. J. Neurosci. (2003) Vol 23 pp 10338-10350 and Renganathan M et al. J. Neurophysiol (2001) Vol 86 pp 629-640) - and also contributes most of the current in subsequent spikes during repetitive firing in DRG neurons (Choi J.S. J. Neurophysiol (2011) Vol 106 pp 3173-3184; and Tan Z.Y. et al. J. Neurosci. (2014) Vol 34 pp 7190-7197).

[0009] Regarding genetic and pharmacology studies, gain-of-function mutations in Navi.8 were found in patients with chronic neuropathic pain such as small fiber neuropathy (Faber C.G. et al. (2012) Ann. Neurol Vol 71 pp 26-39; Han C et al. J. Neurol Neurosurg Psychiatry (2014) Vol 85 pp 499-505; and, Kist A.M. et al. PLoS One (2016) Vol 11 e0161789); Eijkenboom I. et al J. Neurol Neurosurg Psychiatry (2019) 90 (3) pp 342-352); loss-of-function (gene knockout) studies in mice reduced pain sensitivity, notably in nociception (Laird J.M. et al. J. Neurosci (2002) J. Neurosci Vol 22 pp 8352-8356; Jarvis M.F. et al Proc Natl Acad Sci USA (2007) Vol 104 pp 8520-8525; Joshi S.K. et al Pain (2006) Vol 123 pp 75-82) and in neuropathic models (Roza C. et al J Physiol (2003) Vol 550 pp 921-926); NavL8-selective small molecule inhibitors reduced pain in rodents, specifically in inflammatory and neuropathic models (Jarvis et al. op. cit.; Kort M.E. et al Bioorg Med Chem Lett (2010) Vol 20 pp 6812-6815; Scanio M.J. et al Bioorg Med Chem (2010) Vol 18 pp 7816-7825; Payne C.E. et al Br J Pharmacol (2015) Vol 172 pp 2654-2670).

[0010] Currently, non-selective Nav channel inhibitors are used to treat epilepsy, cardiac arrhythmia, and chronic pain (Hille, B. J. Gen. Physiol. (1977) Vol. 69 pp. 497-515; Hille. B, Ion Channels of Excitable Membranes (1992) pp. 391-421; Sunderland, Mass., Sinauer Associates, Inc. 3rded.; Hondeghem L.M. and Katzung B.G. Annu. Rev. Pharmacol. Toxicol. (1984) Vol. 24. Pp. 387-423; Catterall W.A. Trends Pharmacol. Sci. (1987) Vol. 8 pp.57-65) - however, all of these analgesics have limited efficacy owing to dose-limiting adverse side-effects related to inhibiting NavL l / Navl.2 / 1.6 (seizure liability), inhibiting NavL4 (muscle weakness / paralysis), inhibiting Nav 1.5 (arrhythmia risk).

[0011] There is a need to develop a NavL8-selective small molecule inhibitor as an effective and safe analgesic.

[0012] It was an object of the invention to provide novel compounds which are inhibitors, preferably selective inhibitors, of Nav L8, and which preferably have advantages over the compounds of the prior art. The novel compounds should in particular be suitable for use in the treatment of pain.

[0013] This object has been achieved by the subject-matter of the patent claims. It was surprisingly found that the compounds according to the invention are highly potent and selective inhibitors of the Navi.8 channel. Further it was surprisingly found that the compounds according to the invention have advantageous properties compared to the Navi.8 inhibitors of the prior art.

[0014] The invention relates to a compound according to general formula (I) wherein

[0015] Li represents O, C(R7)2-O, O-C(R7)2, N(R7), C(R7)2-N(R7), N(R7)-C(R7)2, S, C(R7)2-S, S-C(R7)2, C(R7)2, or C(R7)2C(R7)2;

[0016] A and B independently from one another represent phenyl, 5- to 10-membered heteroaryl, Ci-6-alkyl, Cs-io-cyclo- alkyl, or 4- to 10-membered heterocycloalkyl;

[0017] R2and R2independently from one another represent F, Cl, Br, CN, Ci-6-alkyl, C>, -e-cycloalky I. NH2, N(H)Ci-4-alkyl, N(Ci-4-alkyl)2, OH, O-Ci-4-alkyl, O-C e-cycloalkyl. SF5, phenyl or C e-cycloalkyk x and y independently from one another represent 0, 1, 2, 3, or 4;

[0018] R4 represents H, Cl, CN, Ci-e-alkyl, or Ce-e-cycloalkyk

[0019] L2represents bond, Ci-3-alkylene, or Ci-2-alkylene-N(H); and

[0020] Rs represents S(=O)Re, S(=O)(=NH)R6, S(=O)2Re, or S(=O)2NH2;

[0021] Re represents Ci.6-alkyl;

[0022] R7represents H, or Ci.4-alkyl; wherein Ci-e-alkyl, Ci-4-alkyl, Ci-4-alkylene, Ci-3-alkylene and Ci-2-alkylene in each case independently from one another is linear or branched, saturated or unsaturated; wherein Ci-e-alkyl, Ci-4-alkyl, Ci-4-alkylene, Ci-3-alkylene, Ci-2-alkylene, C iu-cycloalkyl. C3-7-cycloalkyl, C3-6- cycloalkyl, Cs-7-cycloalkyl, 4- to 10- membered heterocycloalkyl, and 4- to 7- membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; Ci-6-alkyl; CF3; CF2H; CFH2; OH; =0; OCF3; OCF2H; OCFH2; O-Ci-6-alkyl; NH2; N(H)(Ci.6-alkyl); N(Ci.6-alkyl)2; SCF3; SCF2H; SCFH2; and S-Ci.6-alkyl; wherein phenyl, 5- to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or poly substituted with one or more substituents selected from F; Cl; CN; Ci-6-alkyl; CF3; CF2H; CFH2; OH; OCF3; OCF2H; OCFH2; O-Ci-6-alkyl; NH2; N(H)(Ci-6-alkyl); and N(Ci.6-al- kyl ; in the form of the free compound or a physiologically acceptable salt thereof. In a preferred embodiment, the compound according to the invention is present in form of the free compound. For the purpose of specification, “free compound” preferably means that the compound according to the invention is not present in form of a salt. Methods to determine whether a chemical substance is present as the free compound or as a salt are known to the skilled artisan such as14N or15N solid state NMR, x-ray diffraction, x-ray powder diffraction, IR, Raman, XPS.1H-NMR recorded in solution may also be used to consider the presence of protonation.

[0023] In another preferred embodiment, the compound according to the invention is present in form of a physiologically acceptable salt. For the purposes of this specification, the term “physiologically acceptable salt” preferably refers to a salt obtained from a compound according to the invention and a physiologically acceptable acid or base.

[0024] According to the invention, the compound according to the invention may be present in any possible form including solvates, cocrystals and polymorphs. For the purposes of this specification, the term “solvate” preferably refers to an adduct of (i) a compound according to the invention and / or a physiologically acceptable salt thereof with (ii) distinct molecular equivalents of one or more solvents.

[0025] Further, the compound according to the invention may be present in form of the racemate, enantiomers, diastereomers, tautomers or any mixtures thereof. The person skilled in the art knows that imidazoles show annular tautomerism.

[0026] The compounds according to the invention may have one or more stereocenter. The person skilled in art knows by looking at a chemical structure whether the depicted compound has one or more stereocenters or not.

[0027] For some compounds according to the invention that have one or more stereocenters and which chemical structures are disclosed in the examples of the present application, the chemical structure includes bold bonds and / or hashed bonds to indicate the relative structural orientation of those substituents connected by the bold bonds and / or hashed bonds to the superior structure. If the bold bonds and / or hashed bonds are depicted in form of a wedge, the absolute stereochemical configuration of the compound is known and thereby indicated. If the bold bonds and / or hashed bonds are depicted as a straight bond (i.e. no wedge), the absolute stereochemical configuration of the compound has not been determined. In that case, the bold bonds and / or hashed bonds merely serve to indicate that this particular compound is present as one enantiomer or one diastereomer (e.g. cis-diastereomer (i.e. mixture of two cis- enantiomers) or trans-diastereomer (i.e. mixture of two trans-enantiomers)). All compounds according to the invention that have one or more stereocenters but which chemical structures disclosed in the examples of the present application do not include bold bonds and / or hashed bonds, are present as a mixture of the respective stereoisomers.

[0028] The invention also includes isotopic isomers of a compound of the invention, wherein at least one atom of the compound is replaced by an isotope of the respective atom which is different from the naturally predominantly occurring isotope, as well as any mixtures of isotopic isomers of such a compound. Preferred isotopes are2H (deuterium),3H (tritium),13C and14C. Isotopic isomers of a compound of the invention can generally be prepared by conventional procedures known to a person skilled in the art.

[0029] According to the invention, the terms “Ci-4-alkyl” and “Ci-e-alkyl” preferably mean acyclic and preferably saturated hydrocarbon residues, which can be linear (i.e. unbranched) or branched and which can be unsubstituted or mono- or polysubstituted (e.g. di- or trisubstituted), and which contain 1 to 4 (i.e. 1, 2, 3 or 4) or 1 to 6 (i.e. 1, 2, 3, 4, 5 or 6) carbon atoms, respectively. Preferably, Ci-4-alkyl and Ci-e-alkyl are saturated. In another preferred embodiment, Ci-4-alkyl and Ci-e-alkyl are unsaturated and are selected from C2-4-alkenyl, C2-e-alkenyl, C2-4-alkynyl and C2-6-alkynyl. Preferred Ci-4-alkyl groups are selected from the group consisting of methyl, ethyl, n-propyl, 2- propyl, n-butyl, isobutyl, sec-butyl and tert-butyl. Preferred Ci-e-alkyl groups are selected from the group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, isobutyl, sec -butyl, tert-butyl, n-pentyl, 2-pentyl, 3 -pentyl, 2- methylbutyl, 3 -methylbutyl, 3-methylbut-2-yl, 2-methylbut-2-yl, 2,2-dimethylpropyl and n-hexyl. Preferred C2.4- alkenyl groups are selected from the group consisting of ethenyl, propenyl and butenyl. Preferred C2-6-alkenyl groups are selected from C2-4-alkenyl. Preferred C2-4-alkynyl groups are selected from the group consisting of ethynyl, propynyl, and butynyl, more preferably propynyl, most preferably prop-l-ynyl. Preferred C2-6-alkynyl groups are selected from C2-4-alkynyl.

[0030] Still further according to the invention, the terms “C3-7-cycloalkyl”, "C e-cycloalkyl". “C5-7 -cycloalkyl” and “C3- 10-cycloalkyl” preferably means monocyclic or polycyclic, preferably monocyclic or bicyclic, aliphatic hydrocarbons containing 3 to 7 (i.e. 3, 4, 5, 6 or 7), 3 to 6 (i.e. 3, 4, 5 or 6), 5 to 7 (i.e. 5, 6 or 7) or 3 to 10 (i.e. 3, 4, 5, 6, 7, 8, 9 or 10) carbon atoms, wherein the hydrocarbons in each case can be saturated or unsaturated (but not aromatic), unsubstituted or mono- or polysubstituted.

[0031] For the purpose of this specification, “polycyclic” and “bicyclic” shall preferably mean fused, bridged or spirocy- clic systems.

[0032] Preferably, C3-7 -cycloalkyl, C e-cycloalkyl. Cs-7-cycloalkyl and Cs-io-cycloalkyl are saturated. C3-7-cycloalkyl, C3- e-cycloalkyl, C5-7 -cycloalkyl and Cs-io-cycloalkyl can be bound to the respective superordinate general structure via any desired and possible ring member of the cycloalkyl group. C3-7-cycloalkyl, C3-6-cycloalkyl, C5-7 -cycloalkyl and C3-io-cycloalkyl can also be fused with further saturated or (partially) unsaturated heterocycloalkyl, aromatic or heteroaromatic ring systems, preferably aromatic ring system, which can in turn be unsubstituted or mono- or polysubstituted, thereby being part of a bi- or polycyclic system having up to 14 ring members. Accordingly, the terms “C3-7-cycloalkyl”, “Cs-e-cycloalkyl”, “C5-7-cycloalkyl” and “Cs-io-cycloalkyl” preferably include monocyclic or polycyclic, preferably monocyclic or bicyclic, aliphatic hydrocarbons containing 3 to 7, 3 to 6, 5 to 7 or 3 to 10 carbon atoms; which are fused with a phenyl moiety. Preferred C3-7 -cycloalkyl groups are selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.2]pentyl, spiro [2.3] hexyl, spiro [3.3] heptyl, bicyclo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo [2.1.1] hexyl, bicyclo [3.1.1] heptyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, bicyclo[4.1.0]heptyl and 2,3-di- hydro- IH-indenyl.

[0033] Preferred C>,. e-cycloalky I groups are selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, spiro[2.2]pentyl, spiro[2.3]hexyl, bicyclo[l.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[2.1. l]hexyl, bicyclo [3.1.0]hexyl and 2,3 -dihydro- IH-indenyl.

[0034] Preferred C5-7-cycloalkyl groups are selected from the group consisting of cyclopentyl, cyclohexyl, cycloheptyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, bicyclo[2.1.0]pentyl, bicyclo [2.1.1] hexyl, bicyclo[3.1.1]hep- tyl, bicyclo[2.2.1]heptyl, bicyclo[3.1.0]hexyl, bicyclo[3.2.0]heptyl, bicyclo[4.1.0]heptyl and 2,3-dihydro-lH-in- denyl.

[0035] Preferred C3-1 o-cycloalky 1 groups are selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, spiro[2.5]octyl, spiro[2.2]pentyl, spiro [2.3] hexyl, spiro[3.3]heptyl, bicy- clo[1.1.0]butyl, bicyclo[2.1.0]pentyl, bicyclo[2.1.1]hexyl, bicyclo [3.1.1] heptyl, bicyclo[2.2.1]heptyl, bicyclo [3.1.0]hexyl, bicyclo[3.2.0]heptyl, bicyclo[2.2.2]octyl, bicyclo[4.1.0]heptyl, 2,3-dihydro-lH-indenyl, 5, 6,7,8- tetrahydroisoquinolinyl, bicyclo[1.1.0]butyl, bicylo[l.l. l]pentyl, bicyclo[2.1.0]pentyl, bicyclo[3.1.0]hexyl, bicy- clo[2.2.0]hexyl, bicyclo[2.1.1]hexyl, 5-oxaspiro[2.4]heptyl, 2-oxaspiro[3.4]octyl, bicyclo [4.1.0] heptyl, bicy- clo[2.2.1]heptyl, bicyclo[3.3.0]octyl, spiro[2.2]pentyl, spiro[2.3]hexyl, spiro[3.3]heptyl, and dispiro[2.0.2.1]hep- tyl; more preferably cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, spiro[2.5]octyl, spiro [2.3] hexyl, spiro [3.3] heptyl, bicyclo [3.1.1] heptyl, bicyclo[2.2.1]heptyl, bicyclo[3.2.0]heptyl, bicy- clo[2.2.2]octyl, bicyclo[4.1.0]heptyl, 2,3-dihydro-lH-indenyl, bicylo[l. l. l]pentyl, bicyclo [2.1.1] hexyl, 5, 6,7,8- tetrahydroisoquinolinyl, 5-oxaspiro[2.4]heptyl, and 2-oxaspiro[3.4]octyl.

[0036] Further according to the present invention, the terms “Ci-4-alkylene”, “Ci-3-alkylene” and “Ci-2-alkylene” relate to linear or branched, preferably linear, and preferably saturated aliphatic residues which are preferably selected from the group consisting of methylene (-CH2-), ethylene (-CH2CH2-), propylene (-CH2CH2CH2- or -C(CH3)2-) and butylene (-CH2CH2CH2CH2-, - CH2C(CH3)2- or-C(CH3)2CH2-), more preferably methylene (-CH2-) and ethylene (-CH2CH2).

[0037] According to the invention, Ci-6-alkyl, Ci-4-alkyl, Ci-4-alkylene, Ci.3-alkylene and Ci.2-alkylene in each case independently from one another is linear or branched, saturated or unsaturated. In a preferred embodiment, Ci-6-alkyl, Ci-4-alkyl, Ci-4-alkylene, Ci.3-alkylene and Ci.2-alkylene in each case independently from one another is linear or branched, and saturated.

[0038] According to the present invention, the terms “4 to 7-membered heterocycloalkyl”, “5 to 7-membered heterocycloalkyl” and “4 to 10-membered heterocycloalkyl” preferably mean monocyclic or polycyclic, preferably mono- cyclic or bicyclic, heterocycloaliphatic saturated or unsaturated (but not aromatic) residues having 4 to 7 (i.e. 4, 5, 6 or 7), 5 to 7 (i.e. 5, 6 or 7), or 4 to 10 (i.e. 4, 5, 6, 7, 8, 9 or 10) ring members, wherein in each case at least one, if appropriate also two or three carbon atoms are replaced by a heteroatom or a heteroatom group each selected independently of one another from the group consisting of O, S, S(=O), S(=O)2, N, NH and N(Ci-4-alkyl) such as N(CH3), wherein the carbon atoms of the ring can be unsubstituted or mono- or polysubstituted. Preferably, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are saturated. The 4 to 7-membered heterocycloalkyl, the 5 to 7-membered heterocycloalkyl and the 4 to 10-membered heterocycloalkyl groups can also be fused with further saturated or (partially) unsaturated cycloalkyl, aromatic or heteroaromatic ring systems, preferably aromatic ring system, which can in turn be unsubstituted or mono- or polysubstituted, if not indicated otherwise, thereby being being part of a bi- or polycyclic system having up to 14 ring members. In a preferred embodiment, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are not fused with further ring systems. Still more preferably, 4 to 7- membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are not fused with further ring systems and are saturated. In another preferred embodiment, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are condensed with further ring systems, preferably phenyl, 5 to 6-membered heteroaryl, or C3.6-cycloylkyl. The 4 to 7-membered heterocycloalkyl, the 5 to 7-membered heterocycloalkyl and the 4 to 10-membered heterocycloalkyl group can be bound to the superordinate general structure via any desired and possible ring member of the heterocycloaliphatic residue if not indicated otherwise. In a preferred embodiment, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl and 4 to 10-membered heterocycloalkyl are bound to the superordinate general structure via a carbon atom. In another preferred embodiment, 4 to 7-membered heterocycloalkyl, 5 to 7-membered heterocycloalkyl, and 4 to 10-membered heterocycloalkyl are bound to the superordinate general structure via a heteroatom, in particular N.

[0039] Preferred 4 to 7-membered heterocycloalkyl groups are selected from the group consisting of 1,1-dioxo tetrahydrothiophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, pyrrolidinonyl, azetidinyl, piperazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-dioxothietanyl, 2,6-dia- zaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imid- azolidinyl, isoxazolidinyl, oxazolidinyl, pyrazolidinyl, and cromanyl.

[0040] Particularly preferred 4 to 7-membered heterocycloalkyl groups are selected from 5 to 7-membered heterocycloalkyl groups. Preferred 5 to 7-membered heterocycloalkyl groups are selected from the group consisting of 1,1- dioxo tetrahydrothiophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, pyrrolidinonyl, piperazinyl, piperazinonyl, piperidinyl, 2,6-diazaspiro[3.3]heptyl, 2,5-diazabicy- clo [2.2.1] heptyl, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, pyrazolidinyl and cromanyl.

[0041] Preferred 4 to 10-membered heterocycloalkyl groups are selected from the group consisting of 1,1-dioxo tetrahydrothiophenyl, 1-oxo thiomorpholinyl, tetrahydropyranyl, oxetanyl, tetrahydrofuranyl, morpholinyl, pyrrolidinyl, pyrrolidinonyl, azetidinyl, piperazinyl, piperazinonyl, piperidinyl, thietanyl, 1,1-dioxothietanyl, 2-ox- aspiro[3.4]octyl, 5-oxaspiro[2.4]heptyl, 2-oxabicyclo[2.1.1]hexyl, 1,1-dioxo thietanyl, 2,3-dihydro-[l,4]diox- ino[2,3-b]pyridyl, tetrahydro-1, 8-naphthyridinyl, 2,6-diazaspiro[3.3]heptyl, 2,5-diazabicyclo[2.2.1]heptyl, azepanyl, dioxepanyl, oxazepanyl, diazepanyl, thiazolidinyl, tetrahydrothiophenyl, tetrahydropyridinyl, thiomorpholinyl, 4-methylpiperazinyl, morpholinonyl, dithiolanyl, dihydropyrrolyl, dioxanyl, dioxolanyl, dihydropyridinyl, dihydrofuranyl, dihydroisoxazolyl, dihydrooxazolyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, pyrazolidinyl, cromanyl, 5,7-dihydrofuro[3,4-b]pyridinyl, and 5,7-dihydrofuro[3,4-d]pyrimidinyl, more preferably tetrahydropyranyl, tetrahydrofuranyl, 2-oxaspiro[3.4]octyl, 5-oxaspiro[2.4]heptyl, 2-oxabicyclo[2.1.1]hexyl, 1,1-dioxo thietanyl, 2,3-dihydro-[l,4]dioxino[2,3-b]pyridyl, tetrahydro-1, 8-naphthyridinyl, 5,7-dihydrofuro[3,4-b]pyr- idinyl, and 5,7-dihydrofuro[3,4-d]pyrimidinyl.

[0042] According to the present invention, the terms “5 to 10-membered heteroaryl” and “5- to 6-membered heteroaryl“ preferably mean a 5, 6, 7, 8, 9 or 10-membered and 5 or 6-membered monocyclic or bicyclic aromatic residue, respectively, which contains at least 1, if appropriate also 2, 3, 4 or 5 heteroatoms, wherein the heteroatoms are each selected independently of one another from the group S, N and O and the heteroaryl residue can be unsubstituted or mono- or polysubstituted, if not indicated otherwise. In the case of substitution on the heteroaryl, the substitutents can be the same or different and be in any desired and possible position of the heteroaryl. The binding to the superordinate general structure can be carried out via any desired and possible ring member of the heteroaryl residue if not indicated otherwise. Preferably, the 5 to 10-membered heteroaryl and 5- to 6-membered heteroaryl are bound to the supraordinate general structure via a carbon atom of the heterocycle. The heteroaryl can also be fused with further saturated or (partially) unsaturated cycloalkyl, or heterocycloalkyl ring systems, which can in turn be unsubstituted or mono- or polysubstituted, thereby being being part of a bi- or polycyclic system having up to 14 ring members. In a preferred embodiment, the 5 to 10-membered heteroaryl and 5- to 6-membered heteroaryl are not fused with further saturated or (partially) unsaturated cycloalkyl, or heterocycloalkyl ring systems. In another preferred embodiment, the 5 to 10-membered heteroaryl and 5- to 6-membered heteroaryl are fused with further saturated or (partially) unsaturated cycloalkyl, or heterocycloalkyl ring systems. Preferably, the 5 to 10-membered heteroaryl is selected from 5- to 6-membered heteroaryl. Preferably, the 5- to 6-membered heteroaryl is selected from the group consisting of pyridyl (i.e. 2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl, pyridazi- nyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, thienyl (thiophenyl), triazolyl, thiadiazolyl, 4,5,6,7-tetrahydro-2H-indazolyl, 2,4,5,6-tetrahydrocyclopenta[c]pyrazolyl, benzofuranyl, benzoimidazolyl, benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzooxazolyl, ben- zooxadiazolyl, quinazolinyl, quinoxalinyl, carbazolyl, quinolinyl, dibenzofuranyl, dibenzothienyl, imidazothia- zolyl, indazolyl, indolizinyl, indolyl, isoquinolinyl, naphthyridinyl, oxazolyl, oxadiazolyl, phenazinyl, phenothiazinyl, phthalazinyl, purinyl, phenazinyl, tetrazolyl andtriazinyl. Particularly preferred 5- to 6-membered heteroaryl are selected from the group consisting of pyridyl (i.e. 2-pyridyl, 3-pyridyl, 4-pyridyl).

[0043] Preferably, the 5- to 10-membered heteroaryl is selected from the group consisting of pyridyl (i.e. 2-pyridyl, 3- pyridyl, 4-pyridyl), pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, furanyl, thienyl (thiophenyl), triazolyl, thiadiazolyl, 4,5,6,7-tetrahydro-2H-indazolyl, 2, 4,5,6- tetrahydrocyclopenta[c]pyrazolyl, benzofuranyl, benzoimidazolyl, benzothienyl, benzothiadiazolyl, benzothiazolyl, benzotriazolyl, benzooxazolyl, benzooxadiazolyl, quinazolinyl, quinoxalinyl, carbazolyl, quinolinyl, 2,3- dihydro-[l,4]dioxino[2,3-b]pyridyl, tetrahydro- 1,8-naphthyridinyl, thieno 13 ,2-blpyridinyl. 5,6,7,8-tetrahydroiso- quinolinyl, 5,7-dihydrofuro[3,4-d]pyrimidinyl, 5,7-dihydrofuro[3,4-b]pyridinyl, dibenzofuranyl, dibenzothienyl, imidazothiazolyl, indazolyl, indolizinyl, indolyl, isoquinolinyl, naphthyridinyl, oxazolyl, oxadiazolyl, phenazinyl, phenothiazinyl, phthalazinyl, purinyl, phenazinyl, tetrazolyl and triazinyl; more preferably pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, thiazolyl, thiadiazolyl, benzothiazolyl, quinolinyl, 2,3-dihydro-[l,4]di- oxino[2,3-b]pyridyl, tetrahydro- 1,8-naphthyridinyl, thieno [3 ,2-b]pyridinyl, 5,6,7,8-tetrahydroisoquinolinyl, 5,7- dihydrofuro[3,4-d]pyrimidinyl, and 5,7-dihydrofuro[3,4-b]pyridinyl.

[0044] In connection with the terms “Ci-e-alkyl”, “Ci-4-alkyl”, “Ci-4-alkylene”, “Ci-3-alkylene”, “Ci-2-alkylene”, “C3-10- cycloalkyl”, “C3-7-cycloalkyl”, "C e-cycloalkyl". "Ck -cycloalkyl". “4- to 10- membered heterocycloalkyl”, and “4- to 7- membered heterocycloalkyf’the term “substituted” refers in the sense of the invention, with respect to the corresponding residues or groups, to the single substitution (monosubstitution) or multiple substitution (polysubstitution), e.g. disubstitution, trisubstitution or tetrasubstitution; more preferably to monosubstitution, disubstitution or trisubstitution; of one or more hydrogen atoms each independently of one another by at least one substituent. In case of a multiple substitution, i.e. in case of polysubstituted residues, such as di- or trisubstituted residues, these residues may be poly substituted either on different or on the same atoms, for example trisubstituted on the same carbon atom, as in the case of CF3, CH2CF3 or disubstituted as in the case of 1,1 -difluorocyclopropyl, or at various points, as in the case of l-chloro-3 -fluorocyclopropyl. The multiple substitution can be carried out using the same or using different substituents. If a residue occurs multiply within a molecule, then this residue can have respectively different meanings for various substituents: if, for example, both R4and Re denote Ci-e-alkyl, then Ci-e-alkyl can e.g. represent methyl for R4and can represent 2-propyl for R6.

[0045] According to the invention, Ci-e-alkyl, Ci.4-alkyl, Ci.4-alkylene, Ci.3-alkylene, Ci.2-alkylene, C3-io-cycloalkyl, C3. 7-cycloalkyl, C3.6-cycloalkyl, C5-7 -cycloalkyl, 4- to 10- membered heterocycloalkyl, 4- to 7- membered heterocycloalkyl, and 5- to 7- membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; Ci-6-alkyl; CF3; CF2H; CFH2; OH; =0; OCF3; OCF2H; OCFH2; O-Ci.6-alkyl; NH2; N(H)(Ci-6-alkyl); N(Ci-6-alkyl)2; SCF3; SCF2H; SCFH2; and S-Ci-6-alkyl; more preferably F; OH; =0; O-Ci-6-alkyl; N(Ci-6-alkyl)2; and S-Ci-6-alkyl.

[0046] Further according to the invention, phenyl, 5- to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; Ci.6-alkyl; CF3; CF2H; CFH2; OH; OCF3; OCF2H; OCFH2; O-Ci.6-alkyl; NH2; N(H)(Ci. e-alkyl); and N(Ci.6-alkyl)2; preferably F; Cl; Ci.6-alkyl; CF3; OH; OCF3; and O-Ci.6-alkyl; most preferably F.

[0047] According to the invention, A and B independently from one another represent phenyl, 5 to 10-membered heteroaryl, Ci-6-alkyl, C3.io-cycloalkyl, or 4- to 10-membered heterocycloalkyl; preferably phenyl, 5 to 10-membered heteroaryl, C3.io-cycloalkyl, or 4- to 10-membered heterocycloalkyl.

[0048] In a preferred embodiment, at least one of A and B represents phenyl or 5- or 6-membered heteroaryl.

[0049] In another preferred embodiment, A represents phenyl, 5- or 6-membered heteroaryl, or C3_- -cycloalkyl, more preferably phenyl or 5- or 6-membered heteroaryl.

[0050] In yet another preferred embodiment, A represents phenyl, thiophenyl, pyridyl, cyclohexyl or cyclobutyl; more preferably phenyl or thiophenyl.

[0051] In still another preferred embodiment, B represents phenyl, 5- to 10-membered heteroaryl, Ci-6-alkyl, C3.io-cyclo- alkyl, or 4- to 10-membered heterocycloalkyl.

[0052] In even another preferred embodiment, B represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, spiro[2.5]octyl, spiro [2.3] hexyl, spiro[3.3]heptyl, bicyclo [3.1.1] heptyl, bicyclo[2.2.1]heptyl, bicy- clo[3.2.0]heptyl, bicyclo[2.2.2]octyl, bicyclo[4.1.0]heptyl, 2,3-dihydro-lH-indenyl, bicylo[l. l.l]pentyl, bicy- clo[2.1.1]hexyl, 5,6,7,8-tetrahydroisoquinolinyl, 5-oxaspiro[2.4]heptyl, 2-oxaspiro[3.4]octyl, tetrahydropyranyl, tetrahydrofuranyl, 2-oxabicyclo[2.1.1]hexyl, 1,1-dioxo thietanyl, 2,3-dihydro-[l,4]dioxino[2,3-b]pyridyl, tetrahydro- 1,8-naphthyridinyl, 5,7-dihydrofuro[3,4-b]pyridinyl, 5,7-dihydrofuro[3,4-d]pyrimidinyl, phenyl, pyridyl, py- rimidinyl, pyridazinyl, pyrazinyl, pyrazolyl, oxazolyl, thiazolyl, thiadiazolyl, benzothiazolyl, quinolinyl, thieno[3,2-b]pyridinyl, methyl, 2-propyl, or isopentenyl.

[0053] According to the invention, Li represents O, C(R-)2-O. O-C(R-)2. N(R7), C(R7)2-N(R7), N(R7)-C(R7)2, S, C(R-)2- S, S-C(R7)2, C(R7)2, or C(R7)2C(R7)2.

[0054] In a preferred embodiment, Li represents O, O-C(R7)2, N(R7), S, or C(R7)2. More preferably, Li represents O, O- CH(CH3), O-CH2, NH, or N(CH3).

[0055] In a preferred embodiment, when Li represents NH, B preferably represents 5 to 10-membered heteroaryl, more preferably 5 or 6-membered heteroaryl, wherein said heteroaryl preferably contains at least one nitrogen. In another preferred embodiment, when Li represents O or O-C(R7)2, B preferably represents Cs-io-cycloalkyl or phenyl.

[0056] According to the invention, R7represents H, or Ci.4-alkyl. In a preferred embodiment, R7represents H or methyl.

[0057] According to the invention, R2and R3 independently from one another represent F, Cl, Br, CN, Ci-6-alkyl, C3-6- cycloalkyl, NH2, N(H)Ci-4-alkyl, N(Ci-4-alkyl)2, OH, O-Ci-4-alkyl, O-C e-cycloalkyl. SF5, phenyl or CVe-cycloal- kyl.

[0058] In a preferred embodiment, R2represents F, Cl, CN, Ci-6-alkyl, or O-Ci-4-alkyl; preferably wherein Ci-e-alkyl and Ci-4-alkyl can in each case independently be unsubstituted, mono-, di- or trisubstituted with F.

[0059] In another preferred embodiment, R3represents F, Cl, Br, OH, CN, Ci.6-alkyl, O-Ci.4-alkyl, O-C3-6-cycloalkyl, SF5, phenyl or C3-6-cycloalkyl; preferably wherein Ci.6-alkyl and Ci.4-alkyl can in each case independently be unsubstituted, mono-, di- or trisubstituted with F; OH; =0; O-Ci-6-alkyl; N(Ci-6-alkyl)2; or S-Ci-e-alkyl.

[0060] In a preferred embodiment, when x and y are 2, 3 or 4; the 2, 3 or 4 entities of R2and the 2, 3 or 4 entities of R3 are not identical. In a particularly preferred embodiment, when x represents 2, one R2will represent F and one R2will represent Cl, or both R2will represent F, or both R2will represent Cl. In a particularly preferred embodiment, when y represents 2, one R3 will represent F and one R3 will represent Cl.

[0061] According to the invention, x and y independently from one another represent 0, 1, 2, 3, or 4. In a preferred embodiment, x and y independently from one another represent 0, 1, 2 or 3; more preferably 0, 1 or 2, most preferably 1 or 2. In a particularly preferred embodiment, x represents 2.

[0062] According to the invention, R4represents H, Cl, CN, Ci-6-alkyl, or C e-cycloalkyl: preferably H or Ci-6-alkyl; more preferably H, CH3, CH2OH, CH2OCH3, CH2N(CH3)2or propynyl. In a particularly preferred embodiment, R4 represents H or CH3.

[0063] According to the invention, L2represents represents bond, Ci-3-alkylene, or Ci.2-alkylene-N(H).

[0064] In a preferred embodiment, L2represents bond or Ci.3-alkylene; more preferably bond, methylene, or ethylene. In a particularly preferred embodiment, L2represents bond.

[0065] According to the invention, R5represents represents, S(=O)Re, S(=O)(=NH)R6, S(=O)2Re, or S(=O)2NH2.

[0066] In a preferred embodiment, R5 represents S(=O)(=NH)R6, S(=O)Re, S(=O)2NH2, or S(=O)2Re; wherein R6represents methyl or 2-propyl.

[0067] According to the invention, R6represents Ci-6-alkyl; more preferably methyl or 2-propyl; most preferably methyl. According to the present invention, the compound accoridng to the invention is preferably selected from the group consisting of

[0068] 1 2-((3 -chloro-4-fluorophenyl)(methoxy)methyl)-4-(methylsulfonyl)- IH-imidazole

[0069] 2 2-((3 -chloro-4-fluorophenyl)(isopropoxy)methyl)-4-(methylsulfonyl)- IH-imidazole

[0070] 3 2-((3 -chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-4-(methylsulfonyl)- IH-imidazole

[0071] 4 2-((3 -chloro-4-fluorophenyl)(cyclobutoxy)methyl)-4-(methylsulfonyl)- IH-imidazole -6 2-((3-chloro-4-fluorophenyl)((4,4-difluorocyclohexyl)oxy)methyl)-4-(methylsulfonyl)-lH- imidazole

[0072] 2-((3-chloro-4-fluorophenyl)(phenoxy)methyl)-4-(methylsulfonyl)-lH-imidazole

[0073] 2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-4-(methylsulfonyl)-lH-imidazole-10 2-((3-chloro-4-fluorophenyl)(4-fluoro-2 -methoxyphenoxy )methyl)-5-(methylsulfonyl)-lH- imidazole 1 2-((3-chloro-4-fluorophenyl)(3-methoxyphenoxy)methyl)-4-methyl-5-(methylsulfonyl)-lH- imidazole 2 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenoxy)methyl)-4-methyl-5-(methylsulfonyl)-lH- imidazole 3 2-((3-chloro-4-fluorophenyl)(4-methoxyphenoxy)methyl)-4-methyl-5-(methylsulfonyl)-lH- imidazole 4 2-((3-chloro-4-fluorophenyl)(4-fluoro-2-methylphenoxy)methyl)-4-methyl-5-(methylsul- fonyl)- IH-imidazole 5-16 2-((3-chloro-4-fluorophenyl)(((cis)-4-methylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 7-18 2-((3-chloro-4-fluorophenyl)(((trans)-4-methylcyclohexyl)oxy)methyl)-5-methyl-4-(methyl- sulfonyl)- IH-imidazole 9-20 2-((3-chloro-4-fluorophenyl)((l-methylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole 1 2-((benzyloxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole2 2-((3-chloro-4-fluorophenyl)((lr,3r)-3-fluorocyclobutoxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 3 2-((3-chloro-4-fluorophenyl)(cyclopropylmethoxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole 4 2-((3-chloro-4-fluorophenyl)(((2S,3S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)oxy)methyl)-

[0074] 5-methyl-4-(methylsulfonyl)-lH-imidazole 5 2-((3-chloro-4-fluorophenyl)((4-ethylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole 6 2-((3-chloro-4-fluorophenyl)((2,3-dihydro-lH-inden-2-yl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 7 2-((3-chloro-4-fluorophenyl)((4,4-dimethylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 8 2-((3-chloro-4-fluorophenyl)(cyclopentyloxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imida- zole 9 2-((3-chloro-4-fluorophenyl)(cyclobutylmethoxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole 0 2-((3-chloro-4-fluorophenyl)((3,3-difluorocyclobutyl)methoxy)methyl)-5-methyl-4-(methyl- sulfonyl)- IH-imidazole 1 2-((3-chloro-4-fluorophenyl)(3-(difluoromethyl)cyclobutoxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 2 2-((3-chloro-4-fluorophenyl)(3-(trifluoromethyl)cyclobutoxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 3 2-((3-chloro-4-fluorophenyl)(3,3-difluorocyclobutoxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole 4 2-((3-chloro-4-fluorophenyl)((2,2-difluorocyclopentyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 5 2-((bicyclo[3.1.0]hexan-3-yloxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 6 2-((3-chloro-4-fluorophenyl)(l-(4-fluorophenyl)ethoxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole 2-((3 -chloro-4-fluorophenyl)(( 1 -methylcyclopentyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0075] IH-imidazole -39 2-((3-chloro-4-fluorophenyl)((4-fluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole -41 2-((3-chloro-4-fluorophenyl)(l-methylcyclobutoxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole -43 2-((3-chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imida- zole -45 2-((3-chloro-4-fluorophenyl)((3-fluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole -47 2-((3 -chloro-4-fluorophenyl)((3 ,3 -difluoro- 1 -methylcyclobutyl)methoxy)methyl)-5-methyl-4-

[0076] (methylsulfonyl)- IH-imidazole 3-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methoxy)me- thyl)pyridine -50 5-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methoxy)me- thyl)-4-methylthiazole 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methoxy)me- thyl)pyridine -53 2-((3-chloro-4-fluorophenyl)((5,6-difluoro-2,3-dihydro-lH-inden-2-yl)oxy)methyl)-5-methyl-

[0077] 4-(methylsulfonyl)- IH-imidazole -55 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methoxy)me- thyl)-5-methylthiazole -57 2-((3-chloro-4-fluorophenyl)((3,5-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0078] IH-imidazole -59 2-(((4-chloro-3-fluorobenzyl)oxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -61 2-((3-chloro-4-fluorophenyl)((2,5-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0079] IH-imidazole -63 2-((3-chloro-4-fluorophenyl)((2,3-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0080] IH-imidazole -65 2-((3-chloro-4-fluorophenyl)((2,4-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0081] IH-imidazole -67 2-(((2-chloro-4-fluorobenzyl)oxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -69 2-((3-chloro-4-fluorophenyl)((3-chlorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole -71 2-((3-chloro-4-fluorophenyl)((4-chlorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole -73 2-((3-chloro-4-fluorophenyl)((3,4-difluoroben-zyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0082] IH-imidazole -75 2-((3-chloro-4-fluorophenyl)((2,6-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0083] IH-imidazole -77 2-(((3-chloro-4-fluorobenzyl)oxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -79 2-((3-chloro-4-fluorophenyl)((4-(trifluoromethyl)benzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -81 2-((3-chloro-4-fluorophenyl)((3-(trifluoromethyl)benzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -83 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methoxy)me- thyl)-6-(trifluoromethyl)pyridine -85 2-[(3-chloro-4-fluorophenyl)({[(trans)-4-methoxycyclohexyl]oxy})methyl]-4-methanesul- fony 1-5 -methyl- IH-imidazole -87 2-[(3-chloro-4-fluorophenyl)({spiro[2.3]hexan-5-yloxy})methyl]-4-methanesulfonyl-5-me- thyl- IH-imidazole -89 2-[(3-chloro-4-fluorophenyl)({spiro[3.3]heptan-2-yloxy})methyl]-4-methanesulfonyl-5-me- thyl- IH-imidazole -91 2-((3-chloro-4-fluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-4-

[0084] (methylsulfonyl)- IH-imidazole -93 2-((3-chloro-4-fluorophenyl)((3-(trifluoromethoxy)benzyl)oxy)methyl)-5-methyl-4-(methyl- sulfonyl)- IH-imidazole -95 2-((3-chloro-4-fluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)methoxy)methyl)-5-me- thyl-4-(methylsulfonyl)-lH-imidazole -97 2-((3-chloro-4-fluorophenyl)(((S)-3,3-difluorocyclopentyl)methoxy)methyl)-5-methyl-4-(me- thy Isulfonyl)- IH-imidazole -99 2-((3-chloro-4-fluorophenyl)(((R)-3,3-difluorocyclopentyl)methoxy)methyl)-5-methyl-4-(me- thy Isulfonyl)- IH-imidazole 0-101 2-[(3-chloro-4-fluorophenyl)({[(cis)-4-methoxycyclohexyl]oxy})methyl]-4-methanesulfonyl-

[0085] 5 -methyl- IH-imidazole 4-105 2-((3-chloro-4-fluorophenyl)(((cis)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-4-

[0086] (methylsulfonyl)- IH-imidazole 6-107 2-((3-chloro-4-fluorophenyl)((4-methylbenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole 8-109 3-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methoxy)me- thyl)-2-methyl-6-(trifluoromethyl)pyridine 0 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclobutyl)methoxy]methyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole 1 2-[(3-chloro-4-fluorophenyl)-(5-oxaspiro[2.4]heptan-2-ylmethoxy)methyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole 2 2-[(3-chloro-4-fluorophenyl)-[(3,3-dimethylcyclobutyl)methoxy]methyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole 3 2-[(3-chloro-4-fluorophenyl)-(3,3-dimethylcyclohexyl)oxymethyl]-5-methyl-4-methylsul- fonyl- IH-imidazole 4 2-[(3-chloro-4-fluorophenyl)-[(4,4-dimethyloxolan-2-yl)methoxy]methyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole 5 2-[(3-chloro-4-fluorophenyl)-[(3-methyl-3-bicyclo[3.1.0]hexanyl)methoxy]methyl]-5-methyl- 4-methylsulfonyl- IH-imidazole 6 2-[(3-chloro-4-fluorophenyl)-[(l-methylcyclobutyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole 7 2-[(3-chloro-4-fluorophenyl)-(2-cyclopropyl-2,2-difluoroethoxy)methyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole 8 2-[(3-chloro-4-fluorophenyl)-[(2-fluoro-l-methylcyclopropyl)methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole 9 2-[(3-chloro-4-fluorophenyl)-(spiro[2.3]hexan-5-ylmethoxy)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole 0 2-[(3-chloro-4-fluorophenyl)-[(l-propan-2-ylcyclopropyl)methoxy]methyl]-4-methyl-5-me- thylsulfonyl-lH-imidazole 1 2-[3-bicyclo[4.1.0]heptanylmethoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole 2 2-[(3-chloro-4-fluorophenyl)-spiro[2.3]hexan-6-yloxymethyl]-5-methyl-4-methylsulfonyl-lH- imidazole 2-[(3-chloro-4-fluorophenyl)-[(l-cyclopropylcyclopropyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0087] 2-[(3-chloro-4-fluorophenyl)-[(3-methyl-l-bicyclo[l.l.l]pentanyl)methoxy]methyl]-5-methyl-

[0088] 4-methylsulfonyl- IH-imidazole

[0089] 2-[(3-chloro-4-fluorophenyl)-(3,3-difluorocyclopentyl)oxymethyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0090] 2-[(3-chloro-4-fluorophenyl)-[3-(trifluoromethyl)cyclohexyl]oxymethyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole

[0091] 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclohexyl)methoxy]methyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole

[0092] 2-[(3-chloro-4-fluorophenyl)-[(l-phenylcyclopropyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0093] 2-[(3-chloro-4-fluorophenyl)-(2,3-dihydro-lH-inden-2-ylmethoxy)methyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0094] 2-[l-bicyclo[2.1.1]hexanylmethoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0095] 2-[(3-chloro-4-fluorophenyl)-(3-cyclopropylcyclobutyl)oxymethyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0096] 2-[2-bicyclo[4.1.0]heptanylmethoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0097] 2-[(3-tert-butylcyclobutyl)oxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsulfonyl- IH-imidazole

[0098] 2-[(3-chloro-4-fluorophenyl)-[(3-cyclopropylcyclobutyl)methoxy]methyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole

[0099] 3-chloro-5-[[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thoxy ] methyl] - 1 ,2-oxazole

[0100] 2-[(3-chloro-4-fluorophenyl)-[rac-(2R,4R)-2-methyloxan-4-yl]oxymethyl]-4-methyl-5-me- thylsulfonyl-lH-imidazole

[0101] 2-[(3-chloro-4-fluorophenyl)-[[rac-(lR,2S)-2-(trifluoromethyl)cyclopropyl]methoxy]methyl]-

[0102] 5-methyl-4-methylsulfonyl-lH-imidazole

[0103] 2-[(3-chloro-4-fluorophenyl)-[[(lS)-2,2-dimethylcyclopropyl]methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0104] 2-[l-bicyclo[2.2.1]heptanylmethoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0105] 2-[(3-chloro-4-fluorophenyl)-[[(2R,3R)-2,3-dimethylcyclopropyl]methoxy]methyl]-4-methyl-

[0106] 5 -methylsulfonyl- IH-imidazole

[0107] 2-[(3-chloro-4-fluorophenyl)-[(l-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)methoxy]methyl]-5- methyl-4-methylsulfonyl- IH-imidazole

[0108] 2-[(2-tert-butylcyclopropyl)methoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0109] 2-[(3-chloro-4-fluorophenyl)-(2,2-difluorospiro[2.3]hexan-5-yl)oxymethyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0110] 2-[(3-chloro-4-fluorophenyl)-[(3-ethyl-l-bicyclo[l.l.l]pentanyl)oxy]methyl]-4-methyl-5-me- thylsulfonyl-lH-imidazole

[0111] 2-[(3-chloro-4-fluorophenyl)-(2,2-difluorospiro[3.3]heptan-6-yl)oxymethyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0112] 2-[(3 -chloro-4-fluorophenyl)-[(3 -propan-2 -yl- 1 -bicyclo [1.1. l]pentanyl)oxy]methyl] -4-methyl-

[0113] 5 -methylsulfonyl- IH-imidazole

[0114] 2-[(3-chloro-4-fluorophenyl)-[[(lR,2R)-2-(4-fluorophenyl)cyclopropyl]methoxy]methyl]-5- methyl-4-methylsulfonyl- IH-imidazole 2-[(3-chloro-4-fluorophenyl)-[(2-phenylcyclopropyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0115] 2-[(3-chloro-4-fluorophenyl)-[[l-(4-fluorophenyl)cyclopropyl]methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0116] 2-[(3-chloro-4-fluorophenyl)-[[3-(l,l-difluoroethyl)-l-bicyclo[l.l.l]pentanyl]oxy]methyl]-5- methyl-4-methylsulfonyl- IH-imidazole

[0117] 2-[(3-chloro-4-fluorophenyl)-[(3-phenylcyclobutyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0118] 2-[(3-chloro-4-fluorophenyl)-[3-(trifluoromethyl)cyclopentyl]oxymethyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole

[0119] 2-[(3-chloro-4-fluorophenyl)-[(4,4-difluorocyclohexyl)methoxy]methyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole

[0120] 2-[(3-chloro-4-fluorophenyl)-[4-(difluoromethyl)cyclohexyl]oxymethyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole

[0121] 2-[(3-chloro-4-fluorophenyl)-[3-(2,2,2-trifluoroethyl)cyclobutyl]oxymethyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0122] 2-[(3-chloro-4-fluorophenyl)-(2-oxaspiro[3.4]octan-6-yloxy)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0123] 2-[(3-chloro-4-fluorophenyl)-[[3-(trifluoromethyl)cyclobutyl]methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0124] 2-[(3-chloro-4-fluorophenyl)-[(lS,2S)-2-fluorocyclopentyl]oxymethyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0125] 2-[(3-chloro-4-fluorophenyl)-[[rac-(lR,2R)-2-methylcyclobutyl]methoxy]methyl]-4-methyl-5- methylsulfonyl- IH-imidazole

[0126] 2-((3-chloro-4-fluorophenyl)((2-(difluoromethyl)cyclopropyl)methoxy)methyl)-5-methyl-4-

[0127] (methylsulfonyl)- IH-imidazole

[0128] 2-[l-bicyclo[2.2.2]octanyloxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsulfonyl-

[0129] IH-imidazole -163 2-[(3-chloro-4-fluorophenyl)-(3-pentylcyclobutyl)oxymethyl]-4-methyl-5-methylsulfonyl-lH- imidazole

[0130] 2-[[(lS,5S,6R)-6-bicyclo[3.2.0]heptanyl]oxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0131] 1-[2-[[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methoxy]me- thy l]pheny 1] -N,N -dimethy Imethanamine

[0132] 2-[(3-chloro-4-fluorophenyl)-[(3-methylphenyl)methoxy]methyl]-4-methyl-5-methylsulfonyl-

[0133] IH-imidazole

[0134] 2-[(3-chloro-4-fluorophenyl)-[(4-methylphenyl)methoxy]methyl]-4-methyl-5-methylsulfonyl-

[0135] IH-imidazole

[0136] 2-[(3-chloro-4-fluorophenyl)-[(2-methylphenyl)methoxy]methyl]-4-methyl-5-methylsulfonyl- IH-imidazole

[0137] 2-[(3-chloro-4-fluorophenyl)-[[l-(difluoromethyl)cyclopropyl]methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0138] 2-[(3-chloro-4-fluorophenyl)-[(4-fluorocyclohexyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0139] 3-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methoxy]thietane

[0140] 1,1 -dioxide

[0141] 2-[(3-chloro-4-fluorophenyl)-[3-(methylsulfanylmethyl)cyclobutyl]oxymethyl]-4-methyl-5- methylsulfonyl- IH-imidazole

[0142] 2-[(3-chloro-4-fluorophenyl)-[[(lR,2R,4R)-5,5-difluoro-2-bicyclo[2.2.1]heptanyl]oxy]me- thyl] -5-methyl-4-methylsulfonyl- IH-imidazole 5-[[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methoxy]me- thy 1] -3 -methyl- 1 ,2-thiazole

[0143] 3-[[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methoxy]me- thy 1] cyclobutane- 1 -carbonitrile

[0144] 2-[(3-chloro-4-fluorophenyl)-[[4-(trifluoromethyl)-2-oxabicyclo[2.1.1]hexan-l-yl]me- thoxy]methyl]-5-methyl-4-methylsulfonyl-lH-imidazole

[0145] 2-[(3-chloro-4-fluorophenyl)-[[l-(trifluoromethyl)-2-oxabicyclo[2.1.1]hexan-4-yl]me- thoxy]methyl]-5-methyl-4-methylsulfonyl-lH-imidazole

[0146] 2-[(3-chloro-4-fluorophenyl)-[[3-(trifluoromethyl)-l-bicyclo[l.l.l]pentanyl]methoxy]methyl]- 5-methyl-4-methylsulfonyl-lH-imidazole

[0147] 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluoro-l-methylcyclobutyl)methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole 2-[(3-chloro-4-fluorophenyl)-[[l-(l,l-difluoroethyl)cyclobutyl]methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0148] 2-[(3-chloro-4-fluorophenyl)-[(l-ethynylcyclopropyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0149] 2-[(3-chloro-4-fluorophenyl)-(2,2-dimethyloxan-4-yl)oxymethyl]-5-methyl-4-methylsulfonyl- IH-imidazole

[0150] 4-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methoxy]cyclohe- xane- 1 -carbonitrile

[0151] 2-[(3-chloro-4-fluorophenyl)-[[l-(trifluoromethyl)cyclopropyl]methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole 2-[(3-chloro-4-fluorophenyl)-[[l-(2,2-difluoroethyl)cyclopropyl]methoxy]methyl]-5-methyl- 4-methylsulfonyl- IH-imidazole

[0152] 2-[(3-chloro-4-fluorophenyl)-[l-(3-chloro-4-fluorophenyl)ethoxy]methyl]-4-methyl-5-methyl- sulfonyl- IH-imidazole

[0153] 2-[(3-chloro-4-fluorophenyl)-[(l-methylcyclopropyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole 2-[(3-chloro-4-fluorophenyl)-[[l-methyl-3-(trifluoromethyl)cyclobutyl]methoxy]methyl]-5- methyl-4-methylsulfonyl- IH-imidazole

[0154] 2-[(3-chloro-4-fluorophenyl)-[(lR,2R)-2-fluorocyclopentyl]oxymethyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole

[0155] 2-[(3-chloro-4-fluorophenyl)-[(3-fluoro-3-methylcyclobutyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0156] 2-[(3-chloro-4-fluorophenyl)-[[l-(fluoromethyl)cyclopropyl]methoxy]methyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0157] 2-[(3-chloro-4-fluorophenyl)-[(3-fluoro-l-bicyclo[l.l.l]pentanyl)methoxy]methyl]-5-methyl- 4-methylsulfonyl- IH-imidazole

[0158] 2-[(3-chloro-4-fluorophenyl)-spiro[2.5]octan-6-yloxymethyl]-5-methyl-4-methylsulfonyl-lH- imidazole

[0159] [4-[[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methoxy]me- thyl]phenyl]-pentafluoro-Z6-sulfane

[0160] 2-[(3-chloro-4-fluorophenyl)-(4-fluoro-3-methylphenoxy)methyl]-4-methyl-5-methylsulfonyl- IH-imidazole ,219,220 N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-fluoroaniline-198 4-chloro-N-((3-chloro-4-fluorophenyl) (4-(methylsulfonyl)-lH-imidazol-2-yl) methyl)aniline-200 5-chloro-N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)pyridin- 2 -amine -202 5-chloro-N-((5-chlorothiophen-2-yl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)pyridin-2 -amine -204 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-6-methylpyridin-2 -amine -206 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trif- luoromethyl)pyridin-2-amine -208 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3,5- difluoropyridin-2 -amine -210 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-4-(trifluoromethyl)pyridin-2 -amine -212 5-bromo-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)pyridin-2 -amine -214 N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4,4-difluorocyc- lohexan-1 -amine -216 3-chloro-N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)aniline-218 N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-fluoropyridin-

[0161] 2 -amine N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-fluoro-N-me- thylaniline 3-chloro-N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-N-me- thylaniline -224 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-3 -methoxypyridin-2-amine -226 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3-flu- oro-5-methylpyridin-2 -amine -228 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)amino)phenol -230 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-me- thy lpyridazin-3 -amine -232 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)pyridin-

[0162] 2 -amine -234 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-

[0163] (difluoromethoxy)pyridin-2 -amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)thiazol-

[0164] 2 -amine -237 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-2-flu- oro-4-methylaniline -239 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-(trif- luoromethy l)py ridin-3 -amine -241 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)pyrimidin-2 -amine -243 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-flu- oropyrimidin-2 -amine -245 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- ethoxypyrimidin-2 -amine -247 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-flu- oropyridin-2 -amine -249 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-

[0165] (difluoromethyl)-5-fluoropyridin-2 -amine -251 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)benzo[d]thiazol-2 -amine -253 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-(trif- luoromethyl)thiazol-2 -amine -255 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)isoqui- nolin-3 -amine 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-6-(difluoromethyl)pyridin-2 -amine -258 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-(trif- luoromethyl)aniline -260 4,5-dichloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)pyridin-2 -amine -262 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-2-flu- oro-4-methoxy aniline -264 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-6-(trifluoromethyl)pyridin-2 -amine -266 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)pyridin-2 -amine -268 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-me- thoxypyridin-2 -amine -270 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-3-fluoropyridin-2 -amine -272 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- ethoxypyridin-2 -amine -274 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trif- luoromethoxy)pyridin-2 -amine -276 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trif- luoromethyl)pyrazin-2 -amine -278 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-(trif- luoromethy l)py ridazin-3 -amine -280 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trif- luoromethyl)pyrimidin-2-amine -282 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-cyc- lopropyl-3 -fluoropyridin-2 -amine -284 3-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-5-fluoropyridin-2 -amine -286 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3-(trif- luoromethyl)aniline -288 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-flu- oro-3 -methylpyridin-2 -amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-me- thyl-5-(trifluoromethyl)pyrazin-2 -amine 4-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)amino)-

[0166] 2-methylpyrimidine-5-carbonitrile -293 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-flu- oro-6-methylpyridin-2 -amine -295 N-[(3-chloro-4-fluorophenyl)(4-methanesulfonyl-5-methyl-lH-imidazol-2-yl)methyl]-5-flu- oro-4-methylpyridin-2 -amine 4-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-6-isopropylpyrimidin-2 -amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4,6-di- methylpyrimidin-2 -amine 5-bromo-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)thiazol-2 -amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3-cyc- lopropy 1-5 -fluo ropy ridin-2 -amine

[0167] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-me- thy 1-5 -(trifluoro methy l)py ridin-3 -amine

[0168] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(triflu- oromethyl)pyridin-2 -amine

[0169] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-2-(triflu- o ro methy l)py ridin-3 -amine

[0170] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-me- thyl-6-(trifluoromethyl)pyridin-3-amine

[0171] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-me- thyl-2-(trifluoromethyl)pyridin-3-amine

[0172] 5-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thy 1] -6-fluoropy ridin-3 -amine

[0173] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-me- thyl-6-(trifluoromethyl)pyridin-3-amine

[0174] 3-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thyl] -5-fluoropyridin-2 -amine

[0175] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-(diflu- o ro methy l)py ridin-3 -amine

[0176] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-2-(triflu- o ro methy l)quinolin-3 -amine

[0177] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(triflu- o ro methy l)py ridin-3 -amine

[0178] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-(triflu- o ro methy l)py ridin-3 -amine

[0179] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-fluoro-

[0180] 6-(trifluoromethyl)pyridin-2-amine

[0181] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-fluoro-

[0182] 4-(trifluoromethyl)pyridin-2-amine

[0183] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-fluoro-

[0184] 3 -(trifluo ro methy l)py ridin-2-amine

[0185] 5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thyl]-6-(trifluoromethyl)pyridin-2 -amine

[0186] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-fluoro-

[0187] 6-(trifluoromethyl)pyridin-2-amine

[0188] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-fluoro-

[0189] 3 -(trifluo ro methy l)isoquinolin- 1 -amine

[0190] 3-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thyl] -6-fluoropyridin-2 -amine

[0191] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(triflu- oromethyl)pyridin-2 -amine

[0192] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-fluoro-

[0193] 6-(trifluoromethyl)pyridin-3-amine

[0194] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(triflu- oromethyl)quinolin-2 -amine

[0195] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-fluoro-

[0196] 6-(trifluoromethyl)pyridin-3-amine

[0197] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(triflu- o ro methy l)isoquinolin- 1 -amine 4-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thy 1] -3 -fluoropy ridin-2 -amine

[0198] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(diflu- oromethy l)py ridin-3 -amine

[0199] 5-chloro-N-[(3-chloro-4-fluorophenyl)-(3,4,6,7-tetrahydropyrano[3,4-d]imidazol-2-yl)me- thyl] -6-methylpyridin-2 -amine

[0200] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(diflu- oromethyl)pyridin-2 -amine

[0201] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-me- thyl-5-(trifluoromethyl)pyridin-2 -amine

[0202] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-2-(triflu- oromethyl)thieno[3,2-b]pyridin-5-amine

[0203] N-[(3 -chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl- lH-imidazol-2-yl)methyl] -6-( 1 , 1 - difluoroethy l)py ridin-3 -amine

[0204] N-[(3 -chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl- lH-imidazol-2-yl)methyl] -2-( 1 , 1 - difluoroethy l)py ridin-3 -amine

[0205] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(triflu- oromethyl)pyridin-2 -amine

[0206] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(pen- tafluoro-Z6-sulfanyl)aniline

[0207] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(pen- tafluoro-Z6-sulfanyl)aniline

[0208] 5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thyl] -4-fluoropyridin-2 -amine

[0209] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(pen- tafluoro-Z6-sulfany 1 )py ridin-3 -amine

[0210] 5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thyl]-4-(trifluoromethyl)pyridin-2 -amine

[0211] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-2-me- thyl-6-(trifluoromethyl)pyridin-3-amine

[0212] 4-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thyl] -6-fluoropyridin-2 -amine

[0213] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-me- thyl-4-(trifluoromethyl)pyridin-2 -amine

[0214] N-[(3 -chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl- lH-imidazol-2-yl)methyl] -5-( 1 , 1 - difluoroethy l)py ridin-3 -amine

[0215] 5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thy 1] -3 -fluoropy ridin-2 -amine

[0216] 4-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thy 1] -5 -(trifluoro methy l)pyridin-2 -amine

[0217] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-fluoro-

[0218] 4-(trifluoromethyl)pyridin-2-amine

[0219] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(diflu- oromethyl)pyridin-2 -amine

[0220] N-[(3 -chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl- lH-imidazol-2-yl)methyl] -3 -me- thyl-5-(trifluoromethyl)pyridin-2 -amine

[0221] N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-fluoro- 3 -methylaniline

[0222] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(diflu- oromethyl)pyridin-2 -amine -350 2-(l-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)ethyl)-4-(methylsulfonyl)-lH-imidazole -354 (2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -358 (2-((3-chloro-4-fluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -362 (2-((3 -chloro-4-fluorophenyl)((3 ,3 -difluorocyclobutyl)methoxy)methyl)-5-methyl- IH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -366 (2-((3-chloro-4-fluorophenyl)((4-fluorobenzyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -370 (2-((3-chloro-4-fluorophenyl)((4,4-difluorocyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -374 (2-((3-chlorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -378 inuno(methyl)(5-methyl-2-((((trans)-4-(trifluoromethyl)cyclohexyl)oxy)(3-(trifluorome- thyl)phenyl)methyl)-lH-imidazol-4-yl)-16-sulfanone -382 inuno(methyl)(5-methyl-2-((((trans)-4-(trifluoromethyl)cyclohexyl)oxy)(4-(trifluorome- thyl)phenyl)methyl)-lH-imidazol-4-yl)-16-sulfanone -386 (2-((3-(difluoromethyl)phenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -390 (2-((3,5-difluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -394 (2-((4-(difluoromethyl)phenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -398 (2-((3-chloro-4-fluorophenyl)((3-(trifluoromethyl)bicyclo[l.l.l]pentan-l-yl)methoxy)methyl)-

[0223] 5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((2-chlorobenzyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((2-methoxybenzyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((2-(difluoromethyl)benzyl)oxy)methyl)-5-methyl-lH-imidazol- 4-yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((7,7-difluorospiro[2.5]octan-4-yl)oxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -406 (2-((4-chloro-3-fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -410 (2-((3-chloro-2,4-difluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -414 (2-((4-chloro-3-fluorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -418 (2-(((3,5-difluoropyridin-2-yl)amino)(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -422 (2-(((5-chloropyridin-2-yl)amino)(3,4-dichloro-2-fluorophenyl)methyl)-5-methyl-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -426 (2-((3,4-dichlorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -430 (2-((3,4-dichloro-2-fluorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -434 (2-((3-chloro-4-fluorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -438 (2-((4-chloro-3-fluorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -442 (2-((3-chloro-2,4-difluorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -446 (2-((3,4-dichloro-2-fluorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -450 (2-((3-chloro-4-fluorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -454 (2-((3,4-dichlorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -458 (2-((3-chloro-4-fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -462 (2-(((5-chloropyridin-2-yl)amino)(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -466 (2-(((5-chloropyridin-2-yl)amino)(3,4-dichlorophenyl)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -470 (2-((3-chloro-4-fluorophenyl)((5-chloro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -474 (2-((3-chloro-4-fluorophenyl)((4-(trifluoromethyl)thiazol-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -478 (2-((3-chloro-4-fluorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -482 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -486 5-chloro-N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-6-(difluoromethyl)pyridin-2 -amine -490 (2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -494 (2-((3-chloro-4-fluorophenyl)((5-chloro-4-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -498 (2-((3-chloro-4-fluorophenyl)((5-chloro-6-cyclopropylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -502 (2-((3-chloro-4-fluorophenyl)((3,5-difluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -505 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-(methyl-d3)pyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -509 N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0224] 5 -methy l-4-(trifluoro methyl)- 1 , 3 -thiazol-2 -amine -513 (2-((3-chloro-4-fluorophenyl)((6-(l,l-difluoroethyl)-5-fluoropyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -517 (2-((3-chloro-4-fluorophenyl)((6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -521 (2-(((5-fluoro-6-methylpyridin-2-yl)amino)(4-(trifluoromethyl)phenyl)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -525 (2-((3,4-dichlorophenyl)((5-fluoro-4-methylpyrimidin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -529 6-(((3,4-dichlorophenyl)(5-methyl-4-(S-methylsulfonimidoyl)-lH-imidazol-2-yl)me- thyl)amino)-2 -methy Inicotinonitrile -533 (2-((3,4-dichlorophenyl)((5-fluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -537 (2-((3-chlorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -541 6-(((3-chloro-4-fluorophenyl)(5-methyl-4-(S-methylsulfonimidoyl)-lH-imidazol-2-yl)me- thyl)amino)-2-methylnicotinonitrile -545 (2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -549 (2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -553 (2-((3-chloro-4-fluorophenyl)((6-ethyl-5-fluoropyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -557 (2-((3-chloro-4-fluorophenyl)((6-cyclopropyl-5-fluoropyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -561 (2-((3-(difluoromethyl)phenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -565 (2-(((5-fluoro-6-methylpyridin-2-yl)amino)(3-(trifluoromethoxy)phenyl)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -569 (2-((3-(difluoromethoxy)phenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -573 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(methoxyme- thyl)-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -577 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(hydroxyme- thyl)-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -581 (2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -585 (2-((3,5-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone -589 (2-((3-chloro-2,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -593 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -597 (2-((3-chloro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -601 (2-((5-chloro-4-fluoro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -605 (2-((5-chloro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -609 (2-((3,4-difluoro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -613 (2-((3-chloro-4-fluorophenyl)((l-methyl-3-(trifluoromethyl)-lH-pyrazol-5-yl)amino)methyl)-

[0225] 5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -617 (2-((4-chloro-3-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -621 (2-((3-chloro-2-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -625 (2-((5-chloro-2-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -629 (2-((3-chloro-5-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -633 (2-((4-(difluoromethyl)phenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -637 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfinyl)-lH-imidazol-2-yl)methyl)-5-flu- oro-6-methylpyridin-2 -amine (2-((3-chloro-4-fluorophenyl)((4-methyl-5-(trifluoromethyl)thiazol-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0226] (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methoxypyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0227] 2-fluoro-5-(((5-fluoro-6-methylpyridin-2-yl)amino)(5-methyl-4-(S-methylsulfonimidoyl)-lH- imidazol-2-yl)methyl)benzonitrile

[0228] N-[[4-(difluoromethyl)phenyl]-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0229] 3,5-difluoropyridin-2-amine

[0230] (2-((3,4-dichloro-2-fluorophenyl)((3,5-difluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0231] (2-((3-chloro-4-fluorophenyl)((4-methoxy-5-methylpyrimidin-2-yl)amino)methyl)-4-methyl-

[0232] 1 H-imidazol-5-yl)(imino)(methyl)-Z6-sulfanone

[0233] (2-((3 -chloro-4-fluorophenyl)((2,3 -dihydro-[ 1 ,4]dioxino [2,3 -b]pyridin-6-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0234] (2-((3-chloro-4-fluoro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0235] 6-(((3-chloro-4-fluorophenyl)(5-methyl-4-(S-methylsulfonimidoyl)-lH-imidazol-2-yl)me- thyl)amino)-3-fluoropicolinonitrile

[0236] (2-(((5-chloro- 1 -methyl- lH-pyrazol-3 -yl)amino)(3 -chloro-4-fluorophenyl)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0237] (2-((3-chloro-4-fluorophenyl)((5-(4-fluorophenyl)thiazol-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0238] 2-((3-chloro-4-fluorophenyl)((6,6-difluorobicyclo[3.1.0]hexan-3-yl)oxy)methyl)-5-methyl-4-

[0239] (methylsulfonyl)- IH-imidazole -651 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazole-4-sulfonamide -653 2-((3-chloro-4-fluorophenyl)((5-fluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazole-4- sulfonamide -655 2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zole-4-sulfonamide -657 2-((3-chloro-4-fluorophenyl)((5-fluoro-4-methylpyrimidin-2-yl)amino)methyl)-5-methyl-lH- imidazole-4-sulfonamide -661 2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-lH-imidazole-4-sulfo- namide -663 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-lH-imidazole-4- sulfonamide -665 2-((3-chloro-4-fluorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)methyl)-lH- imidazole-4-sulfonamide

[0240] 2-((3-chlorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-lH-imidazole-4- sulfonamide

[0241] 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(hydroxyme- thyl)- lH-imidazole-4-sulfonamide -669 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(methoxyme- thyl)- lH-imidazole-4-sulfonamide -671 2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-lH-imidazole-4-sulfona- mide -673 2-((3 -chloro-4-fluorophenyl)((3 ,3 -difluorocyclobutyl)methoxy)methyl)-5-methyl- IH-imida- zole-4-sulfonamide

[0242] 2-((3-chlorophenyl)((4,4-difluorocyclohexyl)oxy)methyl)-lH-imidazole-4-sulfonamide

[0243] N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonylmethyl)-lH-imidazol-2-yl]methyl]-

[0244] 5-fluoro-6-methylpyridin-2 -amine 5-chloro-N-[(4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]pyridin-2 -amine (2-(((4,4-difluorocyclohexyl)oxy)(4-fluorophenyl)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0245] (2-((4-fluorophenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0246] N-[(3,5-difluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-3,5- difluoropyridin-2 -amine

[0247] (2-((3-fluorophenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0248] 3.5-difluoro-N-[(3-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]pyridin-2 -amine imino(2-((3-methoxyphenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-4-methyl-lH-imida- zol-5-yl)(methyl)-16-sulfanone

[0249] 3.5-difluoro-N-[(3-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]pyridin-2 -amine

[0250] N-[[3-(difluoromethyl)phenyl]-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0251] 3.5-difluoropyridin-2-amine

[0252] 3.5-difluoro-N-[[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]-[4-(trifluorome- thyl)phenyl]methyl]pyridin-2-amine

[0253] 3.5-difluoro-N-[[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]-[3-(trifluorome- thyl)phenyl]methyl]pyridin-2-amine

[0254] (2-((2-fluorophenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0255] (2-((2-(difluoromethyl)phenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0256] 5-fluoro-6-methyl-N-[[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]-phenylme- thyl]pyridin-2 -amine

[0257] 5-fluoro-N-[(4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0258] 6-methylpyridin-2 -amine

[0259] 5-fluoro-N-[(3-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0260] 6-methylpyridin-2 -amine

[0261] 5-fluoro-N-[(3-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thy 1] -6-methylpyridin-2 -amine

[0262] 5-fluoro-N-[(4-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thy 1] -6-methylpyridin-2 -amine

[0263] 5-fluoro-N-[(2-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thy 1] -6-methylpyridin-2 -amine

[0264] 5-chloro-N-[(5-chlorothiophen-2-yl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]pyridin-2 -amine

[0265] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(diflu- oromethoxy)pyridin-2 -amine

[0266] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-cyc- lopropyl-3 -fluoropyridin-2 -amine

[0267] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-fluoro-

[0268] 5 -(trifluoro methy l)py ridin-2-amine

[0269] 2-[(3-chloro-4-fluorophenyl)-[(7,7-difluoro-3-bicyclo[4.1.0]heptanyl)oxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0270] 2-[(3 -chloro-4-fluorophenyl)-( 1 -cyclo hexyletho xy)methyl] -4-methyl-5-methylsulfonyl- 1H- imidazole 2-((3-chloro-4-fluorophenyl)((2-fluorocyclohexyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-

[0271] IH-imidazole

[0272] 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-me- thyl- lH-imidazole-4-sulfonamide

[0273] 2-[(3-chloro-4-fluorophenyl)-(2-methylcyclohexyl)oxymethyl]-4-methyl-5-methylsulfonyl-

[0274] IH-imidazole

[0275] (2-((4,4-difluorocyclohexyl)(4-fluoro-3-methylphenoxy)methyl)-4-methyl-lH-imidazol-5- yl)(imino)(methyl)-16-sulfanone

[0276] (2-((3-chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0277] 2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-methyl-lH- imidazole-4-sulfonamide

[0278] 2-[(3-chloro-4-fluorophenyl)-(2,2-difluorospiro[2.5]octan-6-yl)oxymethyl]-5-methyl-4-me- thylsulfonyl-lH-imidazole

[0279] 2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-methyl-lH- imidazole-4-sulfonamide

[0280] 2-[(3-chloro-4-fluorophenyl)-[(4,4-difluoro-l-methylcyclohexyl)methoxy]methyl]-5-methyl-

[0281] 4-methylsulfonyl- IH-imidazole

[0282] 2-[(3-chloro-4-fluorophenyl)-[(3-fluorophenyl)methoxy]methyl]-5-methyl-4-methylsulfonyl- IH-imidazole

[0283] (2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0284] 2-[(3-chloro-4-fluorophenyl)-(2 -methoxy cyclohexyl)oxymethyl]-4-methyl-5-methylsulfonyl- IH-imidazole

[0285] 2-[(3-chloro-4-fluorophenyl)-[(5-fluoro-2,3-dihydro-lH-inden-2-yl)oxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole

[0286] 2-[(3-chloro-4-fluorophenyl)-[(4-propan-2-ylphenyl)methoxy]methyl]-4-methyl-5-methylsul- fonyl- IH-imidazole

[0287] 2-[(3-chloro-4-fluorophenyl)-[(2-methylpyrazol-3-yl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole

[0288] N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0289] 5 -(trifluo ro metho xy )py ridin-2-amine

[0290] N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0291] 5 -(difluo ro metho xy )py ridin-2-amine

[0292] 5-chloro-N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-6-(trideuteriomethyl)pyridin-2 -amine

[0293] 5-chloro-N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- y 1] methyl] -4-methy Ipy ridin-2-amine

[0294] N-[(3,4-dichlorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-3,5- difluoro -6 -methy Ipy ridin-2 -amine

[0295] N-[(3-chloro-2,4-difluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thy 1] -3,5 -difluo ro-6-methy Ipy ridin-2 -amine

[0296] 5-chloro-N-((3-chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)-4-methylpyrimidin-2 -amine

[0297] N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(diflu- oro methy l)-5 -fluoropy ridin-2-amine

[0298] N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0299] 4-( 1 , 1 -difluoroethyl)- 1 , 3 -thiazol-2 -amine

[0300] 5-chloro-N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl] - 1 ,3 -thiazol-2 -amine (2-((3-chloro-4-fluorophenyl)((4-(difluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0301] 2-[(3 -chloro-4-fluorophenyl)-( 1 -cyclopropylethoxy)methyl] -4-methyl-5-methylsulfonyl- 1H- imidazole

[0302] 5-chloro-N-[(3,4-dichlorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl] -4-methylpyrimidin-2 -amine

[0303] (2-((3-chloro-4-fluorophenyl)((4,4-difluoro-2-methylcyclohexyl)oxy)methyl)-4-methyl-lH- imidazol-5-yl)(imino)(methyl)-16-sulfanone

[0304] (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0305] N-[(5-chloro-4-fluoro-2-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-5-fluoro-6-methylpyridin-2 -amine

[0306] N-[(4-chloro-2-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]-5-fluoro-6-methylpyridin-2 -amine

[0307] N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0308] 5-fluoro-4,6-dimethylpyrimidin-2 -amine

[0309] N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0310] 5-fluoro-4-methoxy-6-methylpyridin-2 -amine

[0311] 3-chloro-N-[(3,4-difluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]-5-fluoro-6-methylpyridin-2 -amine

[0312] (2-((3,4-difluorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0313] (2-(((5-cyclopropoxy-6-methylpyridin-2-yl)amino)(3,4-difluorophenyl)methyl)-lH-imidazol-

[0314] 4-yl)(imino)(methyl)-16-sulfanone

[0315] (2-(((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)(3,4-difluorophenyl)methyl)-4-(methoxy- methyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone

[0316] (2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-4-(me- thoxymethyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone

[0317] (2-((3-chlorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)-lH-imida- zol-4-yl)(imino)(methyl)-16-sulfanone

[0318] (2-((3,4-dichlorophenyl)((4,4-difluorocyclohexyl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0319] (2-(((5-fluoro-6-methylpyridin-2-yl)amino)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0320] (2-((3-chlorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-4-(methoxyme- thyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone

[0321] (2-((3-chloro-4-fluorophenyl)((5,7-dihydrofuro[3,4-b]pyridin-2-yl)amino)methyl)-4-methyl- lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone

[0322] (2-((3-chloro-4-fluorophenyl)((5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)amino)methyl)-4-me- thyl-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone

[0323] N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0324] 5,6-difluoropyridin-2-amine

[0325] (2-(((4,4-difluorocyclohexyl)oxy)(3,4-difluorophenyl)methyl)-4-methyl-lH-imidazol-5- yl)(imino)(methyl)-16-sulfanone

[0326] [6-[[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thy 1] amino] -3 -fluoropy ridin-2-y 1] methanol

[0327] N-[(3-chloro-4-fluorophenyl)-[5-[(dimethylamino)methyl]-4-(methylsulfonimidoyl)-lH- imidazol-2-yl]methyl]-5-fluoro-6-methylpyridin-2 -amine

[0328] N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-

[0329] 5-fluoro-4-methoxy-6-methylpyrimidin-2 -amine 776 2-[(3-chlorophenyl)-[(5-fluoro-6-methylpyridin-2-yl)amino]methyl]-N-methyl-lH-imidazole- 4-sulfonamide

[0330] 777 2-[(3,4-difluorophenyl)-[(5-fluoro-6-methylpyridin-2-yl)amino]methyl]-5-(methoxymethyl)- lH-imidazole-4-sulfonamide

[0331] 778 2-[(3-chlorophenyl)-[[5-(difluoromethoxy)-6-methylpyridin-2-yl]amino]methyl]-lH-imida- zole-4-sulfonamide

[0332] 779 2-[(3,4-dichlorophenyl)-[(5-fluoro-4-methylpyrimidin-2-yl)amino]methyl]-4-methyl-lH- imidazole-5-sulfonamide

[0333] 780 2-[(3 ,4-dichlorophenyl)-( 1 , 1 -dioxothietan-3 -yl)oxymethyl] -5 -methyl- lH-imidazole-4-sulfona- mide

[0334] 782 (2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone

[0335] 783 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclobutyl)methoxy]methyl]-5-(methoxymethyl)- lH-imidazole-4-sulfonamide

[0336] 784 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclobutyl)methoxy]methyl]-4-(hydroxymethyl)- lH-imidazole-5-sulfonamide

[0337] 785 2-((3,4-difhiorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)-lH-imida- zole-4-sulfonamide

[0338] 786 2-(((5-cyclopropoxy-6-methylpyridin-2-yl)amino)(3,4-difluorophenyl)methyl)-lH-imidazole- 4-sulfonamide

[0339] 787 2-((3-chlorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)-lH-imida- zole-4-sulfonamide

[0340] 788 2-((3-chlorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)methyl)-lH-imida- zole-4-sulfonamide

[0341] 789 2-((3-chlorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-5-(methoxyme- thyl)- lH-imidazole-4-sulfonamide

[0342] 790 2-((3-chloro-4-fluorophenyl)(3-(trifluoromethyl)cyclobutoxy)methyl)-5-methyl-lH-imidazole- 4-sulfonamide

[0343] 791 2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazole-4- sulfonamide

[0344] 792 2-((3,4-dichlorophenyl)((5-fluoro-4-methylpyrimidin-2-yl)amino)methyl)-5-methyl-lH-imida- zole-4-sulfonamide

[0345] 793 2-((3-chlorophenyl)((5-fluoropyridin-2-yl)amino)methyl)-5-(l,l-difluoroethyl)-lH-imidazole- 4-sulfonamide

[0346] 794 2-((4-chlorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-lH-imidazole-4- sulfonamide

[0347] 795 2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-lH- imidazole-4-sulfonamide in the form of the free compound or a physiologically acceptable salt thereof.

[0348] In a preferred embodiment, the compound according to the invention is an inhibitor of Nav1.8. In the sense of the invention, the term "inhibitor of Nav1.8" preferably means that the respective compound exhibits in a patch clamp assay an IC50 value on Navi.8 of at most 10 pM (10-10-6mol / L); more preferably at most 1 pM; still more preferably at most 500 nM (IO-9mol / L); even more preferably at most 100 nM; and most preferably at most 10 nM.

[0349] A preferred assay for testing compounds for their potency and method for determining an IC50 on Navi.8 is described in the experimental part down below. In a preferred embodiment, the compound according to the invention is a selective inhibitor of Nav 1.8. In the sense of the invention, the term " selective inhibitor of Nav 1.8 " preferably means that the respective compound preferably does not exhibit any inhibitory activity on Navi.1, Navl.2, Navi.4, Navi.5 and Navl.6. The skilled artisan knows suitable ways to determine whether a compound exhibits inhibitory effects on any of Navl. l, NavE2, NavE4, Nav1.5 and Nav1.6.

[0350] The invention therefore relates to a compound according to the invention for use in the inhibition of Nav 1.8.

[0351] Therefore, another aspect of the invention relates to a compound according to the invention for use in the treatment of pain. Still another aspect of the invention relates to a method of treatment of pain; comprising the administration of a therapeutically effective amount of a compound according to the invention to a subject in need thereof, preferably a human.

[0352] A further aspect of the invention relates to a compound according to the invention as medicament.

[0353] Another aspect of the invention relates to a pharmaceutical dosage form comprising a compound according to the invention. Preferably, the pharmaceutical dosage form comprises a compound according to the invention and one or more pharmaceutical excipients such as physiologically acceptable carriers, additives and / or auxiliary substances; and optionally one or more further pharmacologically active ingredient. Examples of suitable physiologically acceptable carriers, additives and / or auxiliary substances are fdlers, solvents, diluents, colorings and / or binders. These substances are known to the person skilled in the art (see H. P. Fiedler, Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik und angrenzende Gebiete, Editio Cantor Aulendoff).

[0354] The pharmaceutical dosage form according to the invention is preferably for systemic, topical or local administration, preferably for oral administration. Therefore, the pharmaceutical dosage form can be in form of a liquid, semisolid or solid, e.g. in the form of injection solutions, drops, juices, syrups, sprays, suspensions, tablets, patches, fdms, capsules, plasters, suppositories, ointments, creams, lotions, gels, emulsions, aerosols or in multiparticulate form, for example in the form of pellets or granules, if appropriate pressed into tablets, decanted in capsules or suspended in a liquid, and can also be administered as such.

[0355] The pharmaceutical dosage form according to the invention is preferably prepared with the aid of conventional means, devices, methods and processes known in the art. The amount of the compound according to the invention to be administered to the patient may vary and is e.g. dependent on the patient's weight or age and also on the type of administration, the indication and the severity of the disorder. Preferably 0.001 to 100 mg / kg, more preferably 0.05 to 75 mg / kg, most preferably 0.05 to 50 mg of a compound according to the invention are administered per kg of the patient's body weight.

[0356] Therefore, another aspect of the invention relates to the pharmaceutical dosage form according to the invention for use in the treatment of pain. Still another aspect of the invention relates to a method of treatment of pain; comprising the administration of a pharmaceutical dosage form according to the invention to a subject in need thereof, preferably a human.

[0357] Examples of the invention can be synthesized preferentially according to the general synthetic schemes below or using chemistry known to the person skilled in the art. General synthesis schemes

[0358] The desired L2-R5moieties (as defined in claim 1) can be obtained also, but not exclusively, by functional group interconversion (FGI) known to the person skilled in the art. Examples of such transformations include but are not limited to the conversion of iodinated or brominated intermediates to e.g. sulfones using sulfinate salts (Synthesis, 2016, 48, 1939-1973) or multi-step procedures to yield intermediate thioethers under transition metal catalysis followed by oxidation to yield sulfoxides (Chem. Rev. 2022, 122, 16110-16293) or sulfoximines (Chem. Eur. J. 2021, 27, 17293-17321). These transformations include but are not limited to conversion of intermediate thioethers into sulfonyl chlorides and further to sulfonamides. Suitable protecting groups, protecting and deprotecting protocols might be used to enable such functional group interconversion (FGI). Suitable protecting groups and relative reactivities are known in the literature and include e.g. SEM, benzyl, Boc, esters groups and TMS among others (T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis, Wiley -Interscience, 2007, 4thedition, 872-893).

[0359] Protection of imidazoles can lead to two different regioisomers. Both regioisomers can generally undergo similar transformation in similar set of condition. In the following schemes only one of the regiosiomers is indicated for clarity. Deprotection of the two regiosiomers will lead to the same final compounds.

[0360] As illustrated in Scheme 1, compounds of the general formula (A) or (B) after deprotonation (preferred bases include LDA) can be added to aldehydes of the general formula (C) to yield alcohols of the general formula (D). When compounds of the general formula (A) with H instead of Hal on the Carbon Atom adjacent to R4 are used, halogenation after the metal-organic addition step is performed. Preferred reagents include NIS.

[0361] Compounds of the general formula (E) can be prepared from compounds of the general formula (D) by functional group interconversion (FGI) known to the person skilled in the art. Compounds of the general formula (E) can be deprotected to yield compounds of general formula (H). Compounds of the general formula (F) can be prepared by oxidation of compounds of general formula (D) using oxidizing agents such MnO2. Compounds of the general formula (G) can be prepared from compounds of the general formula (F) by functional group interconversion (FGI) known to the person skilled in the art.

[0362] Scheme 1: A, R2, R4, Rs, L2, and x are as defined in claim 1. PG = protecting group, Hal = I, Br. As illustrated in Scheme 2, compounds of the general formula (I-a) can be prepared from compounds of the general formula (H) using amines of general formula (J) under acid catalysis. Suitable acids include e.g. pTSA. Compounds of the general formula (I-b) can be prepared from compounds of the general formula (H) by treatment with alcohols (K) under acid catalysis. Suitable acids include e.g. pTSA.

[0363] Scheme 2: A, B, R2, R3, R4, Rs, R7, L2, n= 0 or 1, x and y are as defined in claim 1.

[0364] As illustrated in Scheme 3, compounds of the general formula (I-b) can be alternatively obtained by treatment of compounds of the general formula (E) with the corresponding alkyl halides (L) followed by deprotection. Compounds of the general formula (I-c) can be alternatively obtained from (E) and (K) using Mitsonobu conditions followed by deprotection. Suitable reagents for the Mitsonubu reaction include DIAD and PPh3.

[0365] Scheme 3: A, B, R2, R3, R4, R5, R7, L2, n= 0 or 1, L2, x and y are as defined in claim 1. PG = protecting group. Hal = I, Br, Cl.

[0366] As illustrated in Scheme 4, compounds of the general formula (I-d) can be prepared by reaction of metal-organic compounds of the general formula (M) with compounds of the general formula (G), subsequent elimination of the intermediate alcohol and concomitant deprotection using acidic conditions (for example in the presence of an acid such as pTSA and heating) followed by hydrogenation of the intermediate double bond. Compounds of the general formula (I-a) can be prepared from compounds of the general formula (G) using a sequence of reductive amination with amines of the general formula (J) followed by deprotection. Reductive amination employs reagents and conditions known to the person skilled in the art. Scheme 4: A, B, R2, R3, R4, Rs, R7, L2, n= 0 or 1, x and y are as defined in claim 1. PG = protecting group.

[0367] As illustrated in Scheme 5, compounds of the general formula (B) can be converted to intermediates of the general formula (P), using reagents of the general formula (O) under conditions employing Pd2(dba)3, Xanthphos and heat in a sealed tube. Intermediates of the general formula (P) can be converted into sulfoximine derivatives where L2- R5is S(=O)(=NH)R6) in the presence of reagents such as diacetoxyiodobenzene and ammonium carbonate.

[0368] Scheme 5: R4, R5, L2, are as defined in claim 1. Hal = I, Br. R!2= R6as defined in claim 1 or protecting group.

[0369] As illustrated in Scheme 6, compounds of the general formula (R-l), (R-2), (R-3) and (R-4) can be obtained from the corresponding compounds of the general formula (A), (B), (P) or (N) in the presence of reagents of the general formula (Q) and aldehydes of the general formula (C) in presence of a base such as sodium carbonate. Compounds of the general formula (S-l), (S-2), (S-3) and (S-4) can be prepared from compounds of the general formula (R- 1), (R-2), (R-3) and (R-4) by alkylating reagents of the general formula (J) or (K) in the presence of acids such as TFA and / or BF3in solvent like dichloromethane at room temperature or under heating, the -OC=ON(RI3)2will act as leaving group. Conversion to (T-l), (T-2), (T-3) and (I) might occur under the same reaction conditions or it might require additional deprotecting steps. Scheme 6: A, B, R2, R3, R4, Rs, R?;L i, n= 0 or 1, x and y are as defined in claim 1, R!2= R6as defined in claim 1 or protecting group, RI3=alkyl.

[0370] As illustrated in Scheme 7, compounds of general formula (R-3-a) can be obtained from compounds of the general formula (R-2) using reagents of the general formula (0-1) under conditions such as the presence of Pd2(dba)3, Xanthphos and heat in a sealed tube. Compounds of general formula (R-3-a) can be converted to compounds of the general formula (R-4-a) in the presence of reagents such as diacetoxyiodobenzene and ammonium carbonate. Compounds of general formula (R-3-a) can be converted to compounds of the general formula (R-4-b) by oxidation in the presence of reagents such as meta-chloroperbenzoic acid in dichloromethane. (R-4-a) and (R-4-b) fall in the general definition of (R-4).

[0371] Scheme 7: A, R2, R4, Re and x are as defined in claim 1. R13 is alkyl.

[0372] As illustrated in Scheme 8, intermediates of the general formula (U) can be prepared from aldehydes of the general formula (C) and primary amines of general formula (J-l). An acid catalyst as pTSA, drying agents such as MgSC>4 and heating can be used to perform such transformation. Deprotonation of compounds of general formula (A), (B), (P) or (N) in the presence of bases such as LDA followed by the addition of intermediates of the general formula (U) yield compounds of the general formula (V-l), (V-2), (V-3) and (V-4). Deprotection of these compounds yields compounds of the general formula (W-l), (W-2), (W-3) and (I-e).

[0373] (W-1 ): Rn = H

[0374] (W-2): Rn = Hal (W-3): Rn = S-R12(l-e): R-n = L2-R5

[0375] Scheme 8: A, B, R2, R3, R4, Rs, L2, x andy are as defined in claim 1 and RI2= Re as defined in claim 1 or protecting group.

[0376] As illustrated in Scheme 9, compounds of the general formula (S-1) can be converted to compounds of the general formula (S-2). Preferred reagents include NIS. Compounds of the general formula (S-3) can be obtained from compounds of the general formula (S-2) by reaction with reagent of general formula (O) under conditions such as the presence of Pd2(dba)3, Xantphos and heat in a sealed tube.

[0377] (S-1) (S-2) (S-3)

[0378] Scheme 9: A, R2, R3, R4, Lbx and y are as defined in claim 1. Hal = I, Br. R] 2= R6as defined in claim 1 or protecting group.

[0379] As illustrated in Scheme 10, compounds of general formula (S-4-a) can be obtained from compounds of the general formula (S-3) in the presence of reagents such as diacetoxyiodobenzene and ammonium carbonate. Compounds of the general formula (S-3), where RI2is a protecting group such as PMB or Bn, can be converted into compounds of the general formula (X) using reagents as for example NCS and acetic acid. Addition of ammonia to compounds of the general formula (X) leads to the formation of compounds of general formula (S-4-c). Compounds of general formula (S-4-a) and (S-4-c) are included in compounds of general formula (S-4).

[0380] Scheme 10: A, B, R2, R3, R4, L 1, x and y are as defined in claim 1. R12 = Re as defined in claim 1 or protecting group.

[0381] As illustrated in Scheme 11, compounds of general formula (S-4) can be converted to compounds of the general formula (I) by deprotection. In case of the SEM protecting group on the imidazole, deprotection might be accomplished under acidic conditions. Compounds of the general formula (S-4-a) and (S-4-c) fall under the general definition of compounds of the general formula (S-4).

[0382] Scheme 11: A, B, R2, R3, R4, Rs, L 1, L2, x and y are as defined in claim 1.

[0383] List of abbreviations

[0384] ABPR= automated back pressure regulation, ACN= acetonitrile, BINAP= 2,2'-bis(diphenylphosphino)-l,l'- binaphthalin, Boc2O= di-tert-butyl dicarbonate, DAST= diethylaminosulfur trifluoride, dba= dibenzylideneacetone, DCE= 1,2-dichloroethane, DCM= dichloromethane; DIAD= diisopropyl azodicarboxylate, DIBAL-H= diisobutylaluminium hydride, DIPEA= V. V-diisopropylcthv lamine, DMF= dimethylformamide, DMAP= 4-dime- thylaminopyridine; DMSO= dimethyl sulfoxide, dppf= l,l'-bis(diphenylphosphino)ferrocene, EA=ethyl acetate, FGI=funtional group interconversion, Hex= hexane, HPLC= high-performance liquid chromatography, IPA= isopropyl alcohol, LCMS= liquid chromatography-mass spectrometry, LDA= lithium diisopropylamide, mCPBA= meta-chloroperoxybenzoic acid, MW= microwave, NCS= N-chlorosuccinimide, NIS= N-Iodosuccinimide, NMR= nuclear magnetic resonance, pet ether=petroleum ether, PG=protecting group, pTSA= -tohicncsulfonic acid, RP= reverse phase, Rt=retention time, rt or RT= room temperature, SEM= 2-(trimethylsilyl)ethoxymethyl, SFC= supercritical fluid chromatography, TBAF= tetra-n-butylammonium fluoride, TBDPS= tert-butyldiphen- ylsilyl, TEA= triethylamine, TFA= trifluoroacetic acid, THF=tetrahydrofurane, TLC= thin layer chromatography, Xantphos= (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane).

[0385] Intermediate 1

[0386] Regioisomeric mixture of 4-iodo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and 5-iodo-l-((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazole

[0387] Sodium hydride (60% dispersion in mineral oil, 0.297 g, 12.372 mmol) was added to a solution of 4-iodo-l / / - imidazole (2.0 g, 10.310 mmol) in dimethylformamide (20 mL) at 0 °C. The mixture was stirred at 0 °C for 1 h followed by the addition of 2-(trimethylsilyl)ethoxymethyl chloride (1.8 mL, 10.3 mmol) at 0 °C. The reaction was stirred at rt for 18 h. The reaction mixture was diluted with ice water (10 mL) and extracted with ethyl acetate (20 mL x 2). The combined organic layers were dried over anhydrous Na2SO i. filtered and concentrated under reduced pressure to get the cmde material which was purified by flash chromatography to afford a regioisomeric mixture of the title compounds (1.7 g, 51%).

[0388] Intermediate 2

[0389] Regioisomeric mixture of 4-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and 5-methyl-l-((2-(tri- methylsilyl)ethoxy)methyl)-lH-imidazole

[0390] The title compound was prepared from 4-methyl-lH-imidazole using an analogous method to that described for intermediate 1. Yield: 5.5 g, 70%. LCMS: m / z [M+H]+= 213.

[0391] Intermediate 3

[0392] Regiosiomeric mixture of (3 -chloro-4-fluorophenyl)(4-iodo- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2- yl)methanol and (3 -chloro-4-fluorophenyl)(5-iodo- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)meth- anol

[0393] LDA (2M sol. in THF / n-heptane / ethylbenzene, 12.4 mL, 24.77 mmol) was added to a solution of 4-iodo-l-((2- (trimcthylsilyl)cthoxy)mcthyl)- 1 / / -imidazole (intermediate 1, 7.3 g, 22.51 mmol) in THF at -78 °C. The reaction was stirred at -78 °C for 1 h followed by the addition of 3-chloro-4-fluorobenzaldehyde (3.570 g, 22.51 mmol). The reaction mixture was stirred at -78 °C for 1 h. The reaction was quenched with sat. NH4C1 solution (50 mL) and extracted with ethyl acetate (100 mL x 2). The combined organic layers were dried over anhydrous Na2SO i. filtered and evaporated to get the crude compound, which was purified by flash chromatography to afford a regioisomeric mixture of the title compounds (7.0 g, 64%). Intermediate 4

[0394] Regioisomeric mixture of (3-chloro-4-fluorophenyl)(4-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol- 2-yl)methanol and (3 -chloro-4-fluorophenyl)(5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2- yl)methanol

[0395] The title compound was prepared from intermediate 2 using an analogous method to that described for intermediate

[0396] 3. Yield: 2.5 g, 29%. LCMS: m / z [M+H]+= 371.

[0397] Intermediate 5

[0398] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(4-(methylsulfonyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methanol and (3-chloro-4-fluorophenyl)(5-(methylsulfonyl)-l-((2-(trimethylsilyl)ethoxy)me- thyl)- lH-imidazol-2-yl)methanol

[0399] L-Proline (262.3 mg, 2.278 mmol) was added to an argon-purged solution of sodium hydroxide (91 mg, 2.28 mmol) in DMSO (30 mL). The mixture was stirred at rt for 30 min followed by the addition of the regioisomeric mixture of intermediate 3 (1.1 g, 2.28 mmol), copper(I) iodide (434 mg, 2.28 mmol) and sodium methane sulfinate (930 mg, 9.14 mmol) at rt. The reaction was heated to 120 °C for 18 h. The reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (50 mL x 2). The organic layers were evaporated under reduced pressure to yield a regioisomeric mixture of the title compounds (0.65 g, crude), which was used in the next step without further purification.

[0400] Intermediate 6

[0401] (3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methanol Intermediate 5 (500 mg, 1.14 mmol) was dissolved in 4 M HC1 in 1,4-dioxane (5 mL) at rt and the mixture was stirred for 18 h. The mixture was concentrated under reduced pressure to get the crude product, which was purified by prep. HPLC to afford the title compound (0.32 g). LCMS m / z = 305 [M+H]+.

[0402] Intermediate 7

[0403] Regiosiomeric mixture of (3 -chloro-4-fluorophenyl)(4-iodo- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2- yl)methanone and (3 -chloro-4-fluorophenyl)(5-iodo- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2- yl)methanol

[0404] To the regioisomeric mixture of intermediate 3 (5.0 g, 10.373 mmol) in THF (100.0 mL) was added MnCP (3.7 g, 41.494 mmol) at rt. The reaction was heated to 60 °C for 16 h. The reaction mixture was filtered through a celite bed and the filtrate was evaporated under reduced pressure to get the cmde product, which was purified by column chromatography to get a regioisomeric mixture of the title (4.0 g, 80%). LCMS m / z = 481 [M+H]+.

[0405] Intermediate 8

[0406] Regioisomeric mixture of (3-chloro-4-fluorophenyl)(4-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazol-2-yl)methanone and (3-chloro-4-fluorophenyl)(5-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methanone

[0407] The regioisomeric mixture of intermediate 7 (4.0 g, 8.333 mmol) in 1,4-dioxane (100.0 mL) was degassed with argon for 10 min. Then NaSMe (0.875 g, 12.5 mmol), Xantphos (0.723 g, 12.5 mmol) and Pd2(dba)s (0.763 g, 0.833 mmol) were added at rt. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to rt and was diluted with ice water. The aqueous part was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine, dried over Na2SC>4 and concentrated under reduced pressure to get the crude product, which was purified by column chromatography to yield a regioisomeric mixture of the title compounds (the title compounds (2.5 g, 74%). LCMS m / z = 401 [M+H]+. Intermediate 9

[0408] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(4-(methylsulfonyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methanone and (3-chloro-4-fluorophenyl)(5-(methylsulfonyl)-l-((2-(trimethylsilyl)ethoxy)me- thyl)- lH-imidazol-2-yl)methanone

[0409] To the regioisomeric mixture of intermediate 8 (1.5 g, 3.732 mmol) in DCM (30.0 mL) was added mCPBA (70% in water; 2.08 g, 9.329 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 2 h. The reaction mixture was quenched with a (1:1) solution of sodium sulfite and sodium bicarbonate solution at 0 °C. The aqueous part was extracted with ethyl acetate (3 x 60 mL). The combined organic layers were washed with brine, dried over Na2SC>4 and concentrated under reduced pressure to get the crude product, which was purified by CombiFlash column chromatography to yield the separated regioisomers.

[0410] Intermediate 9a: major regioisomer (0.9 g, 55%). LCMS m / z = 433 [M+H]+, Rt= 3.88 min, LCMS method A

[0411] Intermediate 9b: minor regioisomer (0.45 g, 27%). LCMS m / z = 433 [M+H]+, Rt= 3.66 min, LCMS method A

[0412] Intermediate 10

[0413] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(5-iodo-4-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1H- imidazol-2-yl)methanol and (3 -chloro-4-fluorophenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methanol

[0414] To a stirred solution of the regioisomeric mixture of intermediate 4 (8.0 g, 21.56 mmol) in MeCN (150 mL) was added NIS (5.83 g, 25.88 mmol) at 0 °C. The reaction mixture was stirred at rt for 16 h. The reaction mixture was quenched with saturated sodium thiosulphate solution and extracted with ethyl acetate (3 x 500 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SC>4 and concentrated under reduced pressure to get the cmde product. The resulting crude was purified by combi-flash column to yield to yield the separated regioisomers.

[0415] Intermediate 10a: major regioisomer (4.5 g, 41%). LCMS m / z = 497 [M+H]+, Rt= 2.14 min, LCMS method B

[0416] Intermediate 10b: minor regioisomer (2.5 g, 23%). LCMS m / z = 497 [M+H]+, Rt= 2.20 min, LCMS method B Intermediate 11

[0417] (3 -chloro-4-fluorophenyl)(5-iodo-4-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methanone or

[0418] (3 -chloro-4-fluorophenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methanone

[0419] To a solution of intermediate 10b (minor regioisomer, 3.5 g, 7.04 mmol) in THF (50 mL) was added MnO2(2.45 g, 28.18 mmol) at rt. The reaction was heated to 80 °C for 16 h. The reaction mixture was cooled to rt and filtered through a sintered funnel. The filtrate was evaporated under reduced pressure to get the crude product, which was purified by combi-flash column chromatography to afford the title compound (2.2 g, 63%). LCMS m / z = 495 [M+H]+.

[0420] Intermediate 12

[0421] (3-chloro-4-fluorophenyl)(4-methyl-5-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2- yl)methanone or (3 -chloro-4-fluorophenyl)(5-methyl-4-(methylthio)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1H- imidazol-2-yl)methanone

[0422] A solution of intermediate 11 (2.2 g, 4.583 mmol) in 1,4-dioxane (70 mL) was degassed with argon for 10 min followed by the addition of NaSMe (0.482 g, 6.875 mmol), Xantphos (0.4 g, 0.687 mmol) and Pd2(dba)3(0.42 g, 0.458 mmol) at rt. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was cooled to rt and diluted with ice water. The aqueous part was extracted with ethyl acetate (3 x 300 mL). The combined organic layers were washed with brine, dried over Na2SO i and concentrated under reduced pressure. The resulting crude product was purified by CombiFlash column chromatography to yield the title compound (1.1 g, 58%). LCMS m / z = 415 [M+H]+.

[0423] Intermediate 13

[0424] (3 -chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2- yl)methanone or (3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methanone

[0425] To a stirred solution of intermediate 12 (1.1 g, 2.644 mmol) inDCM (30 mL) was added mCPBA (77%, 1.8 g, 7.9 mmol) at 0 °C. The reaction was stirred at rt for 5 h. The reaction mixture was quenched with saturated Na2SO3:Na- HCO3 (1:1) solution and extracted with ethyl acetate (2 x 300 mL). The combined organic layers were dried over Na2SO4and evaporated under reduced pressure to get the crude product, which was purified by combi-flash column chromatography to yield the title compound (1.0 g, 84%). LCMS m / z = 447 [M+H]+.

[0426] Intermediate 14

[0427] Regioisomeric mixture of 4-iodo-5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and 5-iodo-4-me- thyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- IH-imidazole

[0428] To a solution of 4-iodo-5-methyl-lH-imidazole (50 g, 240.39 mmol) in dimethylformamide (250 mL) at 0 °C was added sodium hydride (9.2 g, 384.62 mmol) portionwise and the mixture was stirred for 30 min. To the reaction mixture was added SEM-C1 (51 mL, 288.46 mmol) at 0 °C and the mixture was then stirred at ambient temperture for 1 h. The reaction mixture was quenched with cold NH4C1 aqueous solution (400 mL) and extracted with ethyl acetate (2 x 600 mL). The combined organic layers were washed with cold water (2 x 300 mL), brine (300 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product which was purified by flash column chromatography (SiO2, 40% EtOAc / hexane) to afford the title compounds (60 g, 74%). LCMS m / z = 339 [M+H]+.

[0429] Intermediate 15

[0430] Regioisomeric mixture of 4-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and 5-methyl-l-((2-(tri- methylsilyl)ethoxy)methyl)-lH-imidazole

[0431] To a stirred solution of intermediate 14 (6 g, 17.738 mmol, 1 equiv.) in THF (100 mL) was added LDA (IM in THF, 26 mL, 26.6 mmol, 1.5 equiv.) at -78 °C and stirred for 1 h, then added 5-chlorothiophene-2-carbaldehyde (3.120 g, 21.285 mmol, 1.2 equiv.) in THF (10 mL) at -78 °C and stirred for 1 h. The reaction mixture was quenched with saturated ammonium chloride (150 mL), extracted with ethyl acetate (2 x 200 mL). Combined organic layers were washed with brine (300 mL), dried over sodium sulfate, and concentrated under reduced pressure to get crude product. The crude product was purified by mesh silica gel column chromatography to afford (5- chlorothiophen-2-yl)(4-iodo-5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methanol (2 g, 58 %).

[0432] Intermediate 16

[0433] Regioisomeric mixture of (5-chlorothiophen-2-yl)(5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsilyl)ethoxy)me- thyl)-lH-imidazol-2-yl)methanol and (5-chlorothiophen-2-yl)(4-methyl-5-(methylsulfonyl)-l-((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazol-2-yl)methanol

[0434] To stirred solution of intermediate 15 (4.0 g, 8.250 mmol, 1 equiv.) and methane sulfinic acid sodium salt, (3.3 g, 33.0 mmol, 4 equiv.) in DMSO (40 mL) were added sodium hydroxide powder (0.330 g, 8.25 mmol, 1 equiv.) and copper(I) iodide, (0.943 g, 4.950 mmol, 0.6 equiv.) under degassed with argon followed by L-Proline (0.950 g, 8.250 mmol, 1 equiv.) at rt. Resulting reaction mixture was stirred at 120 °C for 16 h. Reaction progress was monitored by TLC and LCMS. The reaction mixture was quenched by ice cold water (100 mL), extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over anhydrous NaiSO i and solvent was evaporated under reduced pressure and it was purified by chromatography to afford the title compound (0.5 g, 14%).

[0435] Intermediate 17

[0436] (5-chlorothiophen-2-yl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methanol

[0437] To a stirred solution of intermediate 16 (0.5 g, 1.144 mmol, 1.0 equiv.) in DCM (5.0 mL) was added HC1 (4N) in 1,4-dioxane (10 mL) at 0 °C. Resulting solution was stirred at rt for 16 h. Reaction progress was monitored by TLC and LCMS. Reaction mass was concentrated under reduced pressure to get crude. Resulting crude was diluted with ethyl acetate (30 mL), washed with sat NaHCO, solution (10 mL), dried over sodium sulfate and removed the solvent under reduced pressure to afford 0.4 g, cmde. LCMS m / z = 307 [M+H]+. Intermediate 18

[0438] Regioisomeric mixture of 5-methyl-4-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and 4-me- thyl-5-(methylthio)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- IH-imidazole

[0439] A stirred solution of inntermediate 14 (mixture of regioisomers, 20 g, 59.13 mmol) in 1,4-dioxane was degassed with argon for 10 minutes followed by the addition of NaSMe (8.3 g, 118.25 mmol), Xantphos (2.05 g, 3.55 mmol) and Pd2(dba)3 (2.17 g, 2.37 mmol). The mixture was heated to 90 °C for 16 h in a sealed tube. The reaction mixture was filtered. The filtrate was concentrated under reduced pressure to obtain a residue which was diluted with water (160 mL) and was extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product which was purified by flash chromatography to the title compounds (10 g, 65%). LCMS m / z = 259 [M+H]+.

[0440] Intermediate 19

[0441] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(5-methyl-4-(methylthio)- 1 -((2-(trimethylsilyl)ethoxy)me- thyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate and (3 -chloro-4-fluorophenyl)(4-methyl-5-(methylthio)- 1 - ((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate

[0442] To a stirred solution of intermediate 18 (mixture of regioisomers, 39 g, 150 mmol) in acetonitrile (200 mL) were added 3-chloro-4-fluorobenzaldehyde (19.7 mL, 165 mmol), diisopropylcarbamic chloride (37 g, 225 mmol) and DIPEA (80 mL, 451 mmol, 3 equiv.). The mixture was stirred at 80 °C for 16 h. The reaction mixture was concentrated under reduced pressure to obtain a residue which was diluted with ethyl acetate (900 mL) and was washed with water (400 mL), brine (35 mL), and was then dried over anhydrous Na2SO i. The Solvent was evaporated under reduced pressure to afford the crude product which was purified by flash chromatography to the title compounds (45 g, 55%). LCMS m / z = 544 [M+H]+.

[0443] Intermediate 20

[0444] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(5-methyl-4-(S-methylsulfonimidoyl)- 1 -((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and (3-chloro-4-fluorophenyl)(4-methyl-5- (S-methylsulfonimidoyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate

[0445] To a stirred solution of intermediate 19 (mixture of regioisomers, 30 g, 55.13 mmol) in MeOH (360 mL) were added diacetoxyiodobenzene (89 g, 275.6 mmol) and ammonium carbonate (17.2 g, 220 mmol) at 0 °C. The mixture was then stirred at ambient temperature for 16 h. The reaction mixture was diluted with ethyl acetate (600 mL), washed with water (300 mL) and brine (200 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4and concentrated under reduced pressure to afford the crude product which was purified by flash chromatography to afford the title compounds (14.2 g, 45%). LCMS m / z = 575 [M+H]+.

[0446] Intermediate 21

[0447] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1H- imidazol-2-yl)methyl diisopropylcarbamate and (3 -chloro-4-fluorophenyl)(5-iodo-4-methyl- 1 -((2-(trimethylsi- lyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate

[0448] To a solution of intermediate 14 (12 g, 35.475 mmol) in acetonitrile (50 mL) were added diisopropylcarbamic chloride (6.38 g, 39.0 mmol), 3-chloro-4-fluorobenzaldehyde (8.4 g, 53.2 mmol) and N,N-diisopropylethylamine (19.6 mL, 106.4 mmol) at ambient temperature. The resulting mixture was heated to 80 °C for 16 h. The reaction mixture was diluted with water (150 mL) and extracted with ethyl acetate (2x150 mL). The combined organic layers were dried over anhydrous NaiSO i. fdtered and concentrated under reduced pressure to afford the crude product, which upon purification by flash chromatography afforded 15 g (68%) of the title compounds. LCMS m / z = 624 [M+H]+.

[0449] Intermediate 22

[0450] Regioisomeric mixture of (4-chloro-3 -fluorophenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- 1H- imidazol-2-yl)methyl diisopropylcarbamate and (4-chloro-3 -fluorophenyl)(5-iodo-4-methyl- 1 -((2-(trimethylsi- lyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate

[0451] The title compounds were prepared from the appropriate precursor (4-chloro-3 -fluorobenzaldehyde) using an analogous method to that described for intermediate 21. LCMS m / z = 624 [M+H]+.

[0452] Intermediate 23

[0453] Regioisomeric mixture of (3 -chloro-2,4-difluorophenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate and (3 -chloro-2,4-difluorophenyl)(5-iodo-4-methyl- 1 -((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate

[0454] The title compounds were prepared from the appropriate precursor 3-chloro-2,4-difluorobenzaldehyde using an analogous method to that described for intermediate 21.

[0455] Intermediate 24

[0456] Regioisomeric mixture of (3 -chloro-2,4-difluorophenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate and (3 -chloro-2,4-difluorophenyl)(5-iodo-4-methyl- 1 -((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate

[0457] The title compounds were prepared from the appropriate precursor 3-chloro-2,4-difluorobenzaldehyde using an analogous method to that described for intermediate 21.

[0458] Intermediate 25

[0459] Regioisomeric mixture of (3 -fluoro-4-(trifluoromethoxy)phenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and (3-fluoro-4-(trifluoromethoxy)phenyl)(5-iodo- 4-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate

[0460] The title compounds were prepared from the appropriate precursor 3-fluoro-4-(trifluoromethoxy)benzaldehyde using an analogous method to that described for intermediate 21. LCMS m / z = 674.1 [M+H]+.

[0461] Intermediate 26

[0462] Regioisomeric mixture of ((3 ,4-dichloro-2-fluorophenyl)(4-iodo-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate and (3 ,4-dichloro-2-fluorophenyl)(5-iodo-4-methyl- 1 -((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate

[0463] The title compounds were prepared from the appropriate precursor 3, 4-dichloro-2 -fluorobenzaldehyde using an analogous method to that described for intermediate 21.

[0464] Intermediate 27

[0465] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)- 1 -((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and (3-chloro-4-fluorophenyl)(4-methyl-5-(methyl- sulfonyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate

[0466] A mixture intermediate 21 (7 g, 11.2 mmol), sodium methanesulfonate (5.3 g, 44.8 mmol), cesium carbonate (3.6 g, 11.2 mmol), L-proline (1.3 g, 11.2 mmol) and copper(I) iodide (1.7 g, 9.0 mmol) inDMSO (80 mL) was stirred at 120 °C for 16 h in a sealed tube. The reaction mixture was cooled to ambient temperature, diluted with water (100 mL) and extracted with ethyl acetate (3x100 mL). The combined organic layers were washed with brine (2x80 mL), dried over anhydrous NaiSO i. filtered, concentrated under reduced pressure purified by chromatography to provided 3.0 g of the title compounds. LCMS m / z = 576 [M+H]+. Intermediate 28

[0467] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)- 1 -((2-(trimethylsilyl)eth- oxy)methyl)- lH-imidazol-2-yl)methanol and (3 -chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)- 1 -((2-(tri- methylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methanol

[0468] To a stirred solution of intermediate 10 (700 mg, 1.4 mmol) in DMSO (20 mL) were added sodium methanesulfinate (575.3 mg, 5.6 mmol), Cs2CO3(459 mg, 1.4 mmol), copper iodide (161 mg, 0.845 mmol) and degassed with argon for 5 minutes prior to the addition of L-Proline (162 mg, 1.4 mmol) and stirred the reaction mixture at 120 °C for 16 h. Reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2^50 mL). Combined organic layer was dried over anhydrous Na2SO i. filtered and concentrated under reduced pressure to obtain crude compound, which upon purification by flash column chromatography (C18, 12 g cartridge, eluted with 0.1% formic acid and acetonitrile) to afford 300 mg (47%) of title compound. LCMS m / z = 449.5 [M+H]+.

[0469] Intermediate 29

[0470] Regioisomeric mixture of 5-chloro-N-((5-chlorothiophen-2-yl)(5-methyl-4-(methylthio)-l-((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)pyridin-2 -amine and 5-chloro-N-((5-chlorothiophen-2-yl)(4-me- thyl-5-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)pyridin-2-amine

[0471] To a stirred solution of Intermediate 16 (1 g, 1.680 mmol, 1 equiv.), Sodium thiomethoxide, 95%, pure (141.4 mg, 2.0 mmol, 1.2 equiv.) in 1,4-dioxane (20 mL) was added Cesium carbonate, 99.5%, for analysis (820 mg, 2.5 mmol, 1.5 equiv.) at RT and degassed with argon for 15 min. To the reaction mixture was added Pd2(dba)3(153.8 mg, 0.168 mmol, 0.1 equiv.) and Xantphos (145.6 mg, 0.25 mmol, 0.15 equiv.) at RT. The resulting reaction mixture was heated to 90 °C and stirred for 2 h at the same temperature under nitrogen atmosphere. The reaction progress was monitored by TLC. The reaction mixture was cooled to RT, diluted with water (50 mL), and extracted with ethyl acetate (3 x 50 mL). Combined organic layers were washed with water (100 mL), brine (100 mL), dried over sodium sulfate and concentrated under reduced pressure to get crude product. The crude product was purified by column chromatography to afford the title compound (650 mg, 75%). Intermediate 30

[0472] Regioisomeric mixture of (3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and (3-chloro-4-fluorophenyl)(4-methyl-5-(methyl- sulfonyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate

[0473] To a stirred solution of Intermediate 21 (40mg, 0.18mmol,lequiv.) in DMSO (4.0 mL) was added MeSO2Na (42mg, 0.27mmol,1.5 equiv.) at room temperature. The reaction mixture was degassed under argon atmosphere, followed by addition of Cui and L-Proline and further degassed under argon atmosphere. The reaction mixture was stirred at 120°C for 36 hours. The reaction mixture was monitored by LCMS. The successful reaction mixtures were quenched with ice cold water and extracted with ethyl acetate (20 mL). Organic layer was washed with water (4mL), brine (10 mL) and dried over Na2SO i Solvent was concentrated under reduced pressure to get crude product which was purified by flash column chromatography on silica gel to get the final product in 46% yield.

[0474] Intermediate 31

[0475] Regioisomeric mixture of 2-((3 -chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)- 1 -((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methoxy)pyridine and 2-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)- l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methoxy)pyridine

[0476] To a stirred solution of Intermediate 28 (100 mg, 0.22 mmol, 1.0 equiv.) in 1,4 dioxane (4 mL) was added KO1Bn (50 mg, 0.44 mmol, 2 equiv.) at 0°C and stirred for 15 min followed by addition of 2-fluoropyridine (32mg, 0.33 mmol ,1.5 equiv.) and was stirred at 100°C for 16 h. The reaction mixture was quenched with water and extracted with ethyl acetate (50 mL). Organic layer was washed with water (10 mL), brine (10 mL) and dried over Na2SO4. Solvent was concentrated under reduced pressure to get cmde product which purified by flash column chromatography to get 68% desired compound.

[0477] Intermediate 32

[0478] 2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-4-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imid- azole and the corresponding SEM regioisomer.

[0479] Step-1: To a stirred solution of Intermediate 4 (4.7 g, 12.67 mmol, 1.0 equiv.) in THF (100 mL), were added 4- fluorophenol (1.4 g, 12.67 mmol, 1.0 equiv.), PPh3(4.0 g, 15.2 mmol, 1.2 equiv.) and Diisopropyl azodicarboxylate (3.0 mL, 15.2 mmol, 1.2 equiv.) at room temperature. The reaction mixture was stirred at room temperature for 16 h. Reaction mixture was concentrated under reduced pressure. Resulting crude was purified by combi flash column chromatography to yield the title compound. Yield: 25.4% (1.5 g, 3.23 mmol). LCMS: m / z [M+H]+= 465.2.

[0480] Intermediate 33

[0481] 2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-5-iodo-4-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-

[0482] IH-imidazole and the corresponding SEM regioisomer

[0483] Step-2: to a stirred solution of the product of Step-1 (7.6 g, 16.34 mmol, 1.0 equiv.) in dimethylformamide (75 mL) was added NIS (4.4 g, 19.61 mmol, 1.2 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 16 h. Reaction mixture was diluted with Na2SO3 solution and extracted with ethyl acetate (3 x 800 mL). Combined organic layer was washed with brine, dried over Na2SO i and concentrated under reduced pressure. Resulting crude was purified by column chromatography to yield the desired compound. Yield: 79% (6 g, 12.90 mmol). LCMS: m / z [M+H]+= 465.2.

[0484] Intermediate 34a and 34b

[0485] 2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-4-methyl-5-(methylthio)-l-((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazole and the corresponding SEM regioisomers

[0486] Step-3: To a stirred solution of the product of Step-2 (4.3 g, 7.28 mmol, 1.0 equiv.) in dioxane (50 mL) was degassed with argon for 10 min followed by the addition of NaSMe (0.8 g, 10.91 mmol, 1.5 equiv.), Xantphos (0.6 g, 1.09 mmol, 0.15 equiv.) andPd2(dba)3(0.7 g, 0.73 mmol, 0.1 equiv.) at room temperature. The reaction mixture was heated at 110 °C for 16 h in a sealed tube. Reaction mixture was cooled to room temperature and diluted with ice water. The resulting mixture was extracted with ethyl acetate (3 x 800 mL). Combined organic layer was washed with brine, dried over Na2SO i and concentrated under reduced pressure. Resulting cmde was first purified by combi flash column chromatography followed by SFC chiral separation. Intermediate 34a (first eluting enantiomer): (1 g, 27%). Intermediate 34b: (second eluting enantiomer): (1 g, 27%). Preparative chiral SFC: column: (R, R)-Whelk-O-1 (21.1 x 250 mm) 5 pm; co-solvent: of 0.3% iPrNFF in n-hexane / MeOH / iPrOH (60:30: 10), flow: 70 mL / min; % of co-solvent: 10%; ABPR: lOObr; T: 35 °C.

[0487] Intermediate 35

[0488] Regioisomeric mixture of 4-iodo-5-(methoxymethyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and 5- iodo-4-(methoxymethyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole

[0489] Step-1: To a starred solution of lH-imidazol-4-ylmethanol hydrochloride (5 g, 37.15 mmol, 1.0 equiv.) in dimethylformamide (50 mL) was cold to 0°C, added DIPEA (17 mL, 94.0 mmol, 2.53 equiv.) followed by SEM-C1 (7.3 mL, 40.87 mmol, 1.1 equiv.) and the reaction mixture was starred at rt for 16 h. The reaction mixture was quenched with water and extracted with ethyl acetate (2x50 mL). The combine organics were washed with brine (50 mL), dried over anhydrous JSfeSCL, filtered and concentrated to get cmde product which was purified by column chromatography (Silica gel 100-200 mesh, 3-4% Methanol in DCM as eluent) to afford (l-((2-(trimethylsilyl) ethoxy) methyl)- lH-imidazol-4-yl) methanol (Regio-isomeric mixture). Yield: 82% (7 g, 30.5 mmol). LC-MS: m / z [M+H]+= 229.

[0490] Step-2: to a stirred solution of the product of Step-1 (7 g, 30.5 mmol, 1.0 equiv.) in THF (100 mL) at 0°C, NaH (60% in oil) (2.5 g, 61.04 mmol, 2.0 equiv.) was added portion wise and stirred at same temperature for 30 min. Mel (2.85 mL, 45.78 mmol, 1.5 equiv.) was added to the reaction mass and stirred at rt for 16h. The reaction mixture was quenched with sat. NH4C1 solution (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organics were washed with brine (50 mL), dried over Na SO i and concentrated under reduced pressure to afford the title compound which was used to next step as such. Yield: 6.2 g (Crude). LC-MS: m / z [M+H]+= 243.

[0491] Intermediate 36

[0492] 4-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazoleor 5-(methylthio)-l-((2-(trimethylsilyl)eth- oxy)methyl)- IH-imidazole

[0493] The intermediate was prepared from intermediate 1 with analogous method to the preparation of intermediate 18. Yield: 54% (4.1 g, 16.77 mmol). LC-MS: m / z [M+H]+= 245. Intermediate 37

[0494] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(5-(methoxymethyl)-4-(methylthio)- 1 -((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and (3-chloro-4-fluorophenyl)(4-(methoxymethyl)- 5-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate

[0495] The title compounds were prepared from the appropriate intermediate and 3, 4-dichloro-2 -fluorobenzaldehyde using an analogous method to that described for intermediate 21.

[0496] Intermediate 38

[0497] 5-chloro-4-fluoro-2 -methoxybenzaldehyde

[0498] Step-1: To a stirred solution of 4-chloro-3-fluorophenol (10.0 g, 68.23 mmol, 1.0 equiv.) was added TFA (65.0 mL) at 0 °C and was added 1,3,5,7-tetraazaadamantane (11.5 g, 81.88 mmol, 1.2 equiv.) in small portions. The mixture was then refluxed overnight at 80 °C, then cooling it at 0 °C followed by addition of cone. H2SO4(0.433 mL) and water (65.0 mL), the reaction was stirred at room temperature for 1 hr. The completion of the reaction was monitored by TLC. The mixture was extracted with DCM, the combined extracts were washed with water and brine, dried over Na2SO i. concentrated and purified by flash chromatography to give 5-chloro-4-fluoro-2-hy- droxybenzaldehyde (2.47 g, 21%). ' HNMR (CDC13, 400 MHz, 25 °C): 5 11.21 (s, 1H), 9.79 (s, 1H), 7.60 (d, J= 7.9 Hz, 1H), 6.78 (d, J= 7.9 Hz, 1H).

[0499] Step-2: To a stirred solution of 5-chloro-4-fluoro-2-hydroxybenzaldehyde (2.43 g, 13.921 mmol, 1.0 equiv.) in dimethylformamide (20.0 mL) were added potassium carbonate (3.848 g, 27.842 mmol, 2.0 equiv.) and methyl iodide (1.7 mL, 27.8 mmol, 2.0 equiv.) at 0 °C and the reaction was stirred at RT for 16h. The completion of the reaction was monitored by LCMS and TLC {20% EtOAc- hexane; Rf 0.4}. The reaction mixture was extracted using ethyl acetate (3 * 25 mL) and water (5 x 15 mL), the organic layer was washed with brine (4 x lO mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure at low temperature to obtain 5-chloro-4-fluoro- 2-methoxybenzaldehyde (2.47 g, 94%). 'HNMR (CDCI3, 400 MHz, 25 °C): 5 10.31 (s, 1H), 7.87 (d, J= 8.6 Hz, 1H), 6.78 (d, J= 10 Hz, 1H), 3.92 (s, 3H). Intermediate 39-60

[0500] The intermediates were prepared from the corrspoding aldehydes in analogous method to the preparation of intermediate 19.

[0501] Intermediate 61

[0502] Regioisomeric mixture of (3 -chloro-4-fluorophenyl)(5-iodo-4-(methylthio)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate and (3 -chloro-4-fluorophenyl)(4-iodo-5-(methylthio)- 1 -((2-(tri- methylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate

[0503] To a stirred solution of compound (3-chloro-4-fluorophenyl)(4-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate Intermediate 50 (3.5 gm , 6.59 mmol, 1.0 equiv.) in acetonitrile (30 mL) was added NIS (4.45 gm , 19.77 mmol, 3.0 equiv.) at RT and stirred at 80 °C for 2h. The reaction mixture was extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure to afford cmde product which was purified by flash column chromatography to afford (3-chloro-4-fluorophenyl)(5-iodo-4-(methylthio)-l-((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate (mixture of regio isomers). Yield: 69% (3 g, 4.57 mmol). LC-MS: m / z [M+H]+ = 656.0. Intermediate 62

[0504] Regioisomeric mixture of methyl 2-((3-chloro-4-fluorophenyl)((diisopropylcarbamoyl)oxy)methyl)-4-(methyl- thio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole-5-carboxylate and methyl 2-((3-chloro-4-fluoro- phenyl)((diisopropylcarbamoyl)oxy)methyl)-5-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole- 4-carboxylate

[0505] To a solution of (3-chloro-4-fluorophenyl)(5-iodo-4-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imid- azol-2-yl)methyl diisopropylcarbamate (Intermediate 61) (3 g, 4.566 mmol, 1.0 equiv.) in MeOH (80 mL) was added triethylamine (13 mL, 91.314 mmol, 20.0 equiv.) and degassed with argon for 10 minutes, followed by addition of Pd(OAc)2 (0.103 g, 0.457 mmol, 0.1 equiv.) and stirred at 70 °C and 120 psi for 16 h in an autoclave under CO atmosphere. The reaction mixture was fdtered over celite bed, washed with ethyl acetate and the filtrate was concentrated under reduced pressure to get crude product which was purified by flash column chromatography to yield methyl 2-((3 -chloro-4-fluorophenyl)((diisopropylcarbamoyl)oxy)methyl)-4-(methylthio)- 1 -((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazole-5-carboxylate (mixture of regio isomers). Yield: 67% (1.8 g, 3.06 mmol). LC-MS: m / z [M+H]+ = 588.2.

[0506] Intermediate 63-86

[0507] The intermediates were prepared from the corrspoding aldehydes in analogous method to the preparation of intermediate 20.

[0508] Intermediate 87

[0509] Regioisomeric mixture of (3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfinyl)-l-((2-(trimethyl- silyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and (3-chloro-4-fluorophenyl)(4-methyl-5- (methylsulfinyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate

[0510] To a solution of (3-chloro-4-fluorophenyl)(5-metiiyl-4-(methylthio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-im- idazol-2-yl)methyl diisopropylcarbamate Intermediate 19 (1.85 g, 3.4 mmol, 1.0 equiv.) in DCM (100 mL) was added mCPBA (920 mg, 3.74 mmol, 1.1 equiv.) at 0 °C and stirred at RT for 2 h. Ca(OH)2(2000 mg) was added to the reaction mixture and stirred at RT for 30 min. Reaction mixture was filtered, washed with ethyl acetate (200 mL). Filtrate was concentrated under reduced pressure, diluted with ethyl acetate (250 mL), washed with water (100 mL) and sat. NaHC'CL solution (100 mL). Organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude product which was purified by column chromatography to afford the desired intermediate. Yield: 89% (1.7 g, 3.04 mmol). LC-MS: m / z [M+H]+= 560.2.

[0511] Intermediate 88

[0512] 7 -difluorospiro [2.5] octan-4-ol

[0513] Step-1: To a stirred solution of l-chloranyl-2-methylsulfanyl-ethane (5.0 g, 36.16 mmol, 1.0 equiv.) was added Mel (11.3 mL, 180.82 mmol, 5.0 equiv.) at RT and was stirred at RT for 36 h. The reaction mixture was concentrated under reduced pressure to afford to crude product which was stirred in a diethyl ether (50 mL) for 30 min. Solid precipitated was filtered, washed with diethyl ether (20 mL), acetone (20 mL) and dried under reduced pressure to afford 2-chloroethyl-di(methyl) sulfonium iodide.

[0514] Step-2: To a stirred of solution of potassium tert-butoxide (1.9 g, 17.15 mmol, 2.0 equiv.) intBuOH (100 mL) was added 4,4-difluorocyclohexan-l-one (1.0 g, 7.45 mmol, 1.0 equiv.) and stirred at RT for 30 min. To the reaction mixture was added (2-chloroethyl)dimethylsulfanium iodide (1.5 g, 5.96 mmol, 0.8 equiv.) portion wise and stirred for 16 h at RT. The reaction mixture was filtered, the filtrate was diluted with water (200 mL) and extracted with ethyl acetate (2 x 200 mL). the combined organic layers were washed with water (200 mL), brine solution (200 mL), dried over sodium sulphate and concentrated under reduced pressure to get crude product which was used in next step without further purification.

[0515] Step-3: To a solution of 7,7-difluorospiro[2.5]octan-4-one (500 mg , 3.12 mmol, 1.0 equiv.) in MeOH (10 mL) was added NaBH4(237 mg, 6.24 mmol, 2.0 equiv.) at 0 °C and stirred at RT for Ih. Reaction mixture was quenched with water (50 mL) and extracted with DCM (100 mL). Organic layer was washed with brine (50 mL), dried over Na2SO4and concentrated under reduced pressure to get crude product which was used without further purification. Intermediate 89

[0516] 5-chloro-6-(difluoromethyl)pyridin-2 -amine

[0517] Step 1: To a stirred solution of 6-bromo-3 -chloropicolinic acid (l g, 4.229 mmol) in THF (15 mL) was added diisobutylaluminium hydride (IM solution in toluene, 10.5 mL) at -78 °C and the mixture was stirred at - 78 °C for 3 h. The reaction mixture was quenched with saturated NH4C1 solution (50 mL) and extracted with ethyl acetate (2 x200 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous NaiSO i. filtered and concentrated under reduced pressure to get the crude compound, which upon purification by flash chromatography afforded 500 mg (53%) of 6-bromo-3-chloropicolinaldehyde.

[0518] Step 2: To a stirred solution of 6-bromo-3-chloropicolinaldehyde (500 mg, 2.268 mmol) in DCM (10 mL) was added diethylaminosulfur trifluoride (1.65 mL) at -78 °C and the reaction mixture was then stirred at ambient temperature for 3 h. The reaction mixture was quenched with saturated NaHCO3solution (20 mL) and extracted with ethyl acetate (2x100 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SC>4, fdtered and concentrated under reduced pressure to obtain the crude compound, which upon purification by flash chromatography afforded 200 mg (36%) of 6-bromo-3-chloro-2-(difluoromethyl)pyridine.

[0519] Step 3: To a stirred solution of 6-bromo-3-chloro-2-(difluoromethyl)pyridine (200 mg, 0.825 mmol) in 1,4-diox- ane (5 mL) at ambient temperature were added tert-Butyl carbamate (386.5 mg) and cesium carbonate (806 mg). The mixture was degassed with argon for 5 min, prior to the addition of xantphos (47 mg) and Pd3(dba)3(37 mg). The mixture was heated to 100 °C for 16 h. The reaction mixture was filtered through a celite pad and the filtrate was diluted with water (10 mL) and extracted with ethyl acetate (2x50 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na3SO4 and filtered. The filtrate was concentrated under reduced pressure to obtain the crude compound, which upon purification by flash chromatography (C18, 12 g cartridge, eluting with 0.1% formic acid and acetonitrile) afforded 180 mg (78%) of tert-butyl (5-chloro-6-(difluorome- thyl)pyridin-2-yl). LCMS m / z = 279 [M+H]+.

[0520] Step 4: To a stirred solution of tert-butyl (5-chloro-6-(difluoromethyl)pyridin-2-yl)carbamate (180 mg) in 1,4 dioxane (2 mL) was added 4 M HC1 in 1,4-dioxane (2 mL) at 0 °C and the reaction mixture was allowed to stirr at ambient temperature for 2 h. The reaction mixture was concentrated under reduced pressure to obtain a residue, which was triturated with diethyl ether (2x20 mL), decanted and dried to obtain 120 mg the title compound as the HC1 salt.

[0521] Intermediate 90

[0522] 3,5-difluoro-6-methylpyridin-2-amine

[0523] Step-1: To a solution of 3,5-difluoropyridine-2,6-diamine (10 g, 68.91 mmol, 1.0 equiv.) in acetic acid (100 mL) was added isobenzofuran- 1,3 -dione (11.3 g, 75.81 mmol, 1.0 equiv.) and stirred at 100 °C for 3 h. The reaction mixture was quenched with water (200 mL), the precipitated solid was filtered, washed with water (100 mL) and dried under reduced pressure to get 2-(6-amino-3,5-difluoropyridin-2-yl)-2,3-dihydro-lH-isoindole-l, 3-dione.

[0524] Yield: 84% (16 g, 58.18 mmol).

[0525] Step-2: To a stirred solution of 2-(6-amino-3,5-difluoropyridin-2-yl)-2,3-dihydro-lH-isoindole-l, 3-dione (16 g, 58.14 mmol, 1.0 equiv.) in acetonitrile (100 mL) were added CuBr (16.68 g, 2.0 equiv.) and tert-butyl nitrite (14 mL, 2.0 equiv.) at 0 °C and was stirred at 80 °C for 6 h. Reaction mixture was concentrated, diluted with ethyl acetate (500 mL), washed with water (150 mL) and brine (150 mL). Organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude product which was purified by column chromatography to afford 2-(6-bromo-3,5-difluoropyridin-2-yl)-2,3-dihydro-lH-isoindole-l, 3-dione. Yield: 51% (10 g, 29.49 mmol).

[0526] Step-3: A mixture of 2-(6-bromo-3,5-difluoropyridin-2-yl)-2,3-dihydro-lH-isoindole-l, 3-dione (15 g, 44.23 mmol, 1.0 equiv.) and 7 M NH3 in MeOH (50 mL) was stirred at RT for 2 h. Reaction mixture was concentrated under reduced pressure to get crude product which was purified by column chromatography afford 6-bromo-3,5- difluoropyridin-2-amine. Yield: 86% (8.0 g, 38.46 mmol).

[0527] Step-4: A mixture of 6-bromo-3,5-difluoropyridin-2-amine (4.0 g, 1.0 equiv.), methyl boronic acid (5.8 g, 5.0 equiv.) and K2CO3 (8.0 g, 3.0 equiv.) in 1,4-dioxane (30 mL) was degassed with argon for 5 min followed by addition of Pd(PPh3)4 (1.10 g, 0.05 equiv.), and was stirred at 100 °C for 16 h. Reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate (150 mL), washed with water (100 mL) and brine (100 mL). Organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude product which was purified by column chromatography to afford 3,5-difluoro-6-methylpyridin-2-amine. Yield: 47% (1.3 g, 9.02 mmol).

[0528] HC1 salt.

[0529] Intermediate 91

[0530] 5 -fluoro -6 -(me thy l-d3 )py ridin-2 -amine

[0531] Step-1: To a stirred solution of 6-bromo-5-fluoropyridin-2-amine (1.7 g, 8.9 mmol, 1.0 equiv.) inDCM (30.0 mL) were added triethylamine (1.86 mL, 13.35 mmol, 1.5 equiv.), 4-dimethylaminopyridine (0.109 g, 0.89 mmol, 0.1 equiv.) and Boc2O (2.5 equiv.) at 0°C and the reaction mixture was stirred at RT for 16 h. After reaction was completed, the reaction mixture was diluted with ethyl acetate (10 mL) and washed with H2O (2 x 10 mL) and brine (2 x 10 mL). Organic extract was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get crude product that was purified by flash chromatography to afford (6-bromo-5-fluoropyridin-2- yl)[tert-butyl(formyl)-{3}-oxidanyl]amino tert-butyl formate (1.7 g, 48%). LC-MS: m / z [M+H]+= 391.1

[0532] Step-2: A mixture of {2-[(6-bromo-5-fluoropyridin-2-yl)[2-(formyloxy)-2-methylpropan-2-yl]amino]-2- methylpropan-2-yl} formate (2.0 g, 5.08 mmol, 1.0 equiv.) in dioxane (4.0 mL) and water (1.0 mL), was degassed with argon for 10 min. (Methyl-d3)boronic acid (1.59 g, 25.4 mmol, 5.0 equiv.), K3PO4 (2.15 g, 10.17 mmol, 2.0 equiv.), and Pd(dppf)Cl2.DCM (0.415 g, 0.509 mmol, 0.1 equiv.) was added at room temperature. The reaction mixture was heated at 110 °C for 16 h in a sealed tube. Reaction mixture was diluted with water (10 mL) and extract with ethyl acetate (2 x 10 mL). Combined organic layer was washed with brine (10 mL), dried over sodium sulphate, and evaporated under reduced pressure to get cmde product. Crude product was purified by flash chromatography to afford {2-[(5-fluoro-6-methylpyridin-2-yl)[2-(formyloxy)-2-methylpropan-2-yl]amino]-2- methylpropan-2-yl} formate (0.6 g, 36%). LC-MS: m / z [M+H]+= 330.1

[0533] Step-3: To a stirred solution of tert-butyl [tert-butyl(formyl)-{3}-oxidanyl](5-fluoro-6-methylpyridin-2-yl)amino formate (0.75 g, 2.26 mmol, 1.0 equiv.) in DCM (10.0 mL) was added TFA (2.0 mL ) at 0°C and the reaction mixture was stirred at RT for 4 h. After reaction was, the reaction mixture was evaporated under reduced pressure and quenched by using NaHCCh solution (10.0 mL), diluted with ethyl acetate (20 mL) and washed with H2O (2 x 10 mL) and brine (2 x 10 mL). Organic extract was dried over anhydrous Na2SO i. filtered and concentrated under reduced pressure to get crude product. Crude product was purified by flash chromatography to afford 5- fhioro-6-methylpyridin-2-amine (0.25 g, 85%). LC-MS: m / z [M+H]+= 130.1.

[0534] Intermediate 92

[0535] 6-( 1 , 1 -difluoroethy l)-5 -fluoropyridin-2 -amine

[0536] Step-1: To a stirred solution of l-(6-bromo-3-fluoropyridin-2-yl)ethan-l-one (2.5 g, 11.47 mmol, 1.0 equiv.) in DCM (30 mL) was drop-wise added Diethylaminosulfur Trifluoride (15 mL, 114.67 mmol, 10.0 equiv.) at 0 °C and stirred at RT for 16 h. The reaction mixture was quenched with NaHCOs, solution at 0 °C and diluted with DCM (50 mL). The organic layer was separated, washed with water (20 mL) and brine (20 mL). Solvent was dried over sodium sulfate and concentrated under reduced pressure to get crude product which was purified by flash column chromatography to get 6-bromo-2-( 1,1 -difluoroethy l)-3 -fluoropyridine. Yield: 29% (800 mg, 3.33 mmol). LC-MS: m / z [M+H]+= 340.9.

[0537] Step-2: A solution of 6-bromo-2-(l,l-difluoroethyl)-3-fluoropyridine (400 mg, 1.67 mmol, 1.0 equiv.) in dioxane (10 mL) was degassed with Argon for 10 min followed by the addition of diphenylmethanimine (604 mg, 3.53 mmol, 2.0 equiv.), Cs2COs (1.1 g, 3.33 mmol, 2.0 equiv.), BINAP (104 mg, 0.17 mmol, 0.1 equiv.), Pd(OAc)2(37 mg, 0.17 mmol, 0.1 equiv.) and was stirred at 100 °C for 16 h in a sealed tube. The reaction mixture was diluted with water (50 mL) and extracted with [M+H]+ (2 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SC>4, and concentrated under reduced pressure to afford cmde product which was purified by flash column chromatography to afford N-(6-(l,l-difluoroethyl)-5-fluoropyridin-2-yl)-l,l-diphenyl- methanimine. LC-MS: m / z [M+H]+= 340.9.

[0538] Step-3: To a solution of N-(6-(l,l-difluoroethyl)-5-fluoropyridin-2-yl)-l,l-diphenylmethanimine (800 mg, 2.35 mmol, 1.0 equiv.) in THF (10 mL) was added 1(N) HO (10 mL) at 0 °C and stirred at RT for 3 h. The reaction mixture was diluted with water (25 mL), neutralized with sat. NaHCOs solution to pH~7 and extracted with [M+H]+ (2x 200 mL). The combined organic layers were washed with brine (50 mL), dried over sodium sulphate, and concentrated under reduced pressure to get crude product which was purified by flash column chromatography to get 6-(l,l-difluoroethyl)-5-fluoropyridin-2 -amine. Yield: 84% (350 mg, 1.98 mmol). LC-MS: m / z [M+H]+= 176.8. Intermediate 93

[0539] 5 -fluoro -4 -me thy Ipy rimidin-2 -amine

[0540] To a solution of 2-chloro-5-fluoro-4-methylpyrimidine (1.0 g, 6.82 mmol, 1.0 equiv.) in 7 M NH3 in MeOH (20 mL) was stirred at 80 °C for 24 h in a sealed tube. Reaction mixture was concentrated under reduced pressure to get crude product which was purified by flash column chromatography to get 5-fluoro-4-methylpyrimidin-2- amine. Yield: 57.7 % (500 mg, 3.93 mmol). LC-MS: m / z [M+H] + = 128.1.

[0541] Intermediate 94

[0542] 6-(difluoromethyl)-5-fluoropyridin-2 -amine

[0543] Step-1: To a solution of 6-chloro-3-fluoropyridine-2-carbaldehyde (3 g, 18.8 mmol, 1.0 equiv.) in DCM (50 mL) was drop-wise added Diethylaminosulfur Trifluoride (4.47 mL, 33.84 mmol, 1.8 equiv.) at -30 °C and was gradually warmed to RT over 4 h. The reaction mixture was quenched with NaHCCL solution (100 mL) at 0 °C, diluted with DCM (200 mL), layers were separated, and organic layer was washed with water (100 mL) and brine (100 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford crude product which was purified by flash column chromatography to afford 6-chloro-2-(difluoromethyl)-3-fluoropyridine. Yield: 73% (2.5 g, 13.8 mmol).

[0544] Step-2: A mixture of 6-chloro-2-(difluoromethyl)-3-fluoropyridine (3 g, 16.52 mmol, 1.0 equiv.), diphenylme- thanimine (5.5 mL, 33.05 mmol, 2.0 equiv.) and Cs2CO3 (10.8 g, 33.05 mmol, 2.0 equiv.) in 1,4-dioxane (60 mL) was degassed with Argon gas for 15 min followed by the addition of BINAP (1029 mg, 1.65 mmol, 0.1 equiv.), Pd(OAc)2 (371 mg, 1.65 mmol, 0.1 equiv.) and stirred at 100 °C for 16 h. The reaction mixture was filtered, washed with ethyl acetate (100 mL), the filtrate was concentrated under reduced pressure, diluted with water (100 mL) and extracted with ethyl acetate (2 x 100 mL). Th combined organic layers were washed with brine (100 mL), dried over Na2SO4and concentrated under reduced pressure to afford cmde product which was purified by flash column chromatography to afford 6-(difluoromethyl)-N-(diphenylmethylidene)-5-fluoropyridin-2-amine. Yield: 78% (4.2 g, 12.88 mmol). LC-MS: m / z [M+H]+ = 327.2.

[0545] Step-3: To a solution of 6-(difluoromethyl)-N-(diphenylmethylidene)-5-fluoropyridin-2 -amine (4.2 g, 12.87 mmol, 1.0 equiv.) in THF (60 mL) was added IN HC1 (60 mL) at 0 °C and stirred at RT for 16 h. The reaction mixture was concentrated under reduced pressure to get a residue which was basified with saturated NaHC'CL solution to pH~8 and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na:SO i and concentrated under reduced pressure to afford cmde product which was purified by flash column chromatography afford 6-(difluoromethyl)-5-fluoropyridin-2 -amine. Yield: 76% (1.6 g, 9.87 mmol). LC-MS: m / z [M+H]+= 163.1. Intermediate 95

[0546] 6-cy clopropy 1-5 -fluo ropy ridin-2 -amine

[0547] Step-1: To a stirred solution of 6-bromo-5-fluoropyridin-2 -amine (1 g, 5.236 mmol, 1 equiv.) in l,4-dioxane:water (15 ml) was added CS2CO3 (5.12 g, 15.707 mmol, 3 equiv.) and degassed with Argon for 5 mins. Cyclopropyl- boronic acid (2.25 g, 26.178 mmol, 5 equiv.) and Pd(dppf)Cl2(0.383 g, 0.524 mmol, 0.1 equiv.) were added and the reaction mixture was stiired at 100°C for 16h. After completion (monitored by LCMS) the reaction mixture was filtered through celite bed, Filtrate was concentrated under reduced pressure to get the crude product which was purified by combiflash chromatography to afford 6-ethyl-5-fluoropyridin-2-amine (0.6 g, 75%). LC-MS: m / z [M+H] + = 153.1.

[0548] Intermediate 96

[0549] 6-cy clopropy 1-5 -fluo ropy ridin-2 -amine

[0550] Step-1: To a stirred solution of 6-bromo-5-fluoropyridin-2 -amine (1 g, 5.236 mmol, 1 equiv.) in l,4-dioxane:water (15 ml) was added K3PO4 (3.33 g, 15.707 mmol, 3 equiv.) and degassed with Argon for 5 mins. Ethylboronic acid (1.93 g, 26.178 mmol, 5 equiv.) and Pd(dppf)C12.DCM(0.428 g, 0.524 mmol, 0.1 equiv.) were added and the reaction mixture was stiired at 100°C for 16h. After completion (monitored by LCMS) the reaction mixture was fdtered through celite bed, Filtrate was concentrated under reduced pressure to get the crude product which was purified by combiflash chromatography to afford 6-ethyl-5-fluoropyridin-2-amine (0.5 g, 68%). LC-MS: m / z [M+H] + = 140.06.

[0551] Intermediate 97

[0552] 4-methoxy-5-methylpyrimidin-2-amine

[0553] Step-1: A solution of 2-chloro-4-methoxy-5-methylpyrimidine (600 mg, 3.78 mmol,l equiv.) in dioxane (8 mL) was degassed with argon for 10 min followed by the addition of diphenylmethanimine (1.4 g, 7.57 mmol, 2.0 equiv.), CS2CO3 (2.4 g, 7.57 mmol, 2.0 equiv.), BINAP (0.23 g, 0.38 mmol, 0.1 equiv.) and Pd(OAc)2(0.085 g, 0.38 mmol, 0.1 equiv.). and stirred at 100 °C for 16 h. Reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2 x 200 mL). Combined organic layers were washed with brine (100 mL), dried over Na2SO i and concentrated under reduced pressure to afford crude product which was purified by flash chromatography to afford N-(diphenylmethylidene)-4-methoxy-5-methylpyrimidin-2-amine. Yield: 31% (360 mg, 1.18 mmol). LC-MS: m / z [M+H]+= 303.7 Step-2: To a solution of N-(diphenylmethylidene)-4-methoxy-5-methylpyrimidin-2-amine (2 g, 6.59 mmol, 1.0 equiv.) in THF (10 mL) was added 1(N) HO (10 mL) at 0 °C and stirred at RT for 2 h. Reaction mixture was neutralised with sat NaHC'CL solution and extracted with ethyl acetate (2 x 200mL). Combined organic layers were washed with brine (50 mL), dried over sodium sulphate and concentrated under reduced pressure to get 4- methoxy-5-methylpyrimidin-2-amine. Yield: 66% (610 mg, 4.38 mmol). LC-MS (Method S): m / z [M+H]+= 139.9.

[0554] Intermediate 98

[0555] (3 -(trifluoromethy l)bicy clo [1.1.1 ]pentan- 1 -y l)methanol

[0556] To a solution of 2.4 (M) LiAlH4in THF (4.6 mL, 11.103 mmol, 2 equiv.) in THF (40 mL) was added 3-(trifluoro- methyl) bicyclo [l.l.l]pentane-l-carboxylic acid (1 gm, 5.55 mmol, 1 equiv.) in THF (1 mL) at 0 °C and stirred at RT for 4 h. The reaction mixture was quenched with 10% aqueous solution of NaOH (2.5 mL) and the precipitated solid was filtered and the filtrate was dried under Na2SO i. concentrated to dryness to the title compound that was used directly in next steps. Yield: 70% (650 mg, 3.91 mmol).

[0557] Intermediate 99

[0558] 4-(benzylthio)-5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and the corresponding SEM regioisomer

[0559] SBn -

[0560] SEM

[0561] A solution of 4-iodo-5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole (mixture of regioisomers, 5 g, 14.78 mmol) in 1,4-dioxane (100 mL) was degassed with argon for 10 min followed by the addition of benzyl mercaptan (3.5 mL, 29.65 mmol), DIPEA (7.7 mL, 44.34 mmol), Xantphos (1.3 g, 2.22 mmol) and Pd2(dba)s (1.4 g, 1.48 mmol) at room temperature. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was filtered and the filtrate was concentrated. The obtained residue was diluted with water (90 mL) and extracted with ethyl acetate (2 x 90 mL). The combined organic layers were washed with brine (70 mL), dried over Na2SO i and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiCL. 50% EtOAc / Hex) to afford the title compounds. Yield: 61% (3 g). LCMS m / z = 335 [M+H]+.

[0562] Intermediates 100-101

[0563] The intermediates were prepared from the corresponding starting materials using an analogous method to the preparation of intermediate 99.

[0564] Intermediate 102

[0565] 5-(((tert-butyldiphenylsilyl)oxy)methyl)-4-((4-methoxybenzyl)thio)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazole and the corresponding SEM regioisomer

[0566] Step 1: A mixture of 4-iodo-lH-imidazole (20 g, 103.11 mmol), sodium acetate (14.4 g, 176.31 mmol), acetic acid (8.8 mL, 154.66 mmol) and 37% HCHO (72 mL) was refluxed for 30 h. The reaction mixture was cooled and extracted with ethylacetate (3 x 150 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SC>4, filtered and concentrated under reduced pressure to get the crude product which was purified by column chromatography (SiO2, 10% MeOH in DCM) to yield (4-iodo-lH-imidazol-5-yl)methanol. Yield: 35% (8.0 g). LCMS m / z = 225[M+H]+.

[0567] Step 2: To a solution of (4-iodo-lH-imidazol-5-yl)methanol (8 g, 35.71 mmol) in dimethylformamide (70 mL) was added sodium hydride (60% in mineral oil, 1.4 g, 35.71 mmol) at 0 °C and the mixture was stirred for 30 min, followed by the addition of SEM-C1 (6.3 mL, 35.71 mmol). The reaction mixture was stirred at room temperature for 16 h and was then quenched with cold NH4C1 solution (50 mL) and extracted with EtOAc (2 x 150 mL). The combined organic layers were washed with cold water (3 x 50 mL), brine (50 mL), dried over sodium sulfate, fdtered and concentrated under reduced pressure to afford crude (4-iodo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazol-5-yl)methanol and the corresponding N-SEM regioisomer. Yield: Quantitative (9 g). LCMS m / z = 355 [M+H]+. Step 3: To a solution of (4-iodo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-5-yl)methanol and the corresponding N-SEM regioisomer (5.5 g, 15.48 mmol) in dimethylformamide (60 mL) were added imidazole (4.2 g, 61.92 mmol) and 4-dimethylaminopyridine (0.38 g, 3.1 mmol) followed by tert-butyl(chlor)diphenylsilan (16.1 mL, 61.92 mmol) at 0 °C and the mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with water (50 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to get the cmde product which was purified by column chromatography (SiC 20% EtOAc / hex) to yield 5-(((tert-butyldiphenylsi- lyl)oxy)methyl)-4-iodo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole and the corresponding SEM regioisomer. Yield: 43% (4 g). LCMS m / z = 593 [M+H]+.

[0568] Step 4: To a solution of 5-(((tert-butyldiphenylsilyl)oxy)methyl)-4-iodo-l-((2-(trimethylsilyl)ethoxy)methyl)-lH- imidazole and the corresponding SEM regioisomer (3.5 g, 5.9 mmol) and (4-methoxyphenyl)methanethiol (0.9 mL, 6.49 mmol) in 1,4-dioxane (40 mL) were added Xantphos (0.51 g, 0.88 mmol) and DIPEA (2.3 mL, 12.97 mmol) followed by purging with argon for 15 min. Pd2dbas (0.54 g, 0.59 mmol) was added and the mixture was heated to 100 °C for 16 h. The reaction mixture was filtered through a celite pad, the pad was washed with ethyl acetate (20 mL) and the filtrate was concentrated under reduced pressure to get the crude product (mixture of regioisomers) which was purified by flash column chromatography (SiCK 50% EtOAc / hex) to yield the title compounds. Yield: 82% (3 g). LCMS m / z = 619 [M+H]+.

[0569] Intermediate 103 l-(3-chloro-4-fluorophenyl)-N-(5-fluoro-6-methylpyridin-2-yl)methanimine

[0570] Step 1: To a solution of 3-chloro-4-fluorobenzaldehyde (5 g, 31.53 mmol) in toluene (50 mL) was added 5-fluoro- 6-methylpyridin-2 -amine (4 g, 31.53 mmol) at room temperature and the mixture was refluxed for 16 h with azeotropic removal of water using a Dean-stark apparatus. The reaction mixture was cooled and was concentrated under reduced pressure to yield the title compound which was used for the next step without further purification Yield: Quantitative (7.0 g). LCMS m / z = 267 [M+H]+.

[0571] Intermediate 104

[0572] (4-(benzylthio)-5-methyl- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)(3 -chloro-4-fluorophenyl)me- thyl diisopropylcarbamate and the corresponding SEM regioisomer To a stirred solution of 4-(benzylthio)-5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole (intermediate 99, mixture of regioisomers, 2.5 g, 1 Al mmol) in acetonitrile (15 mL) were added 3-chloro-4-fluorobenzaldehyde (1 mL, 8.22 mmol), diisopropylcarbamic chloride (1.8 g, 11.21 mmol) and DIPEA (4 mL, 22.42 mmol) at room temperature. The resulting solution was stirred at 80 °C for 16 h. The reaction mixture was then concentrated. The obtained residue was diluted with ethyl acetate (200 mL), was washed with water (80 mL), followed by brine (80 mL), dried over anhydrous NaiSO i and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (SiCK 10% EtOAc / Hex) to afford the title compounds. Yield: 76% (3.5 g, 5.64 mmol). LCMS m / z = 620 [M+H]+.

[0573] Intermediate 105-107

[0574] The intermediates were prepared from the corrspoding aldehydes in analogous method to the preparation of intermediate 104.

[0575] Intermediate 108

[0576] (4-(benzylthio)-5-(methoxymethyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)(3-chloro-4-fluoro- phenyl)methyl diisopropylcarbamate and the corresponding SEM regioisomer

[0577] Step 1 : To a stirred solution of lH-imidazol-4-ylmethanol hydrochloride (5 g, 37.15 mmol) in dimethylformamide (50 mL) at

[0578] 0 °C was added DIPEA (17 mL, 94.0 mmol) followed by SEM-C1 (7.3 mL, 40.87 mmol) and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with water and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, fdtered and concentrated to get the crude product which was purified by column chromatography (SiO2, 3-4% Methanol in DCM) to afford (l-((2-(trimethylsilyl) ethoxy) methyl)- lH-imidazol-4-yl) methanol and the corresponding N-SEM regioisomer. Yield: 82% (7 g). LCMS m / z = 229 [M+H]+.

[0579] Step 2: To a stirred solution of (l-((2-(trimethylsilyl) ethoxy) methyl)- lH-imidazol-4-yl) methanol and the corresponding N-SEM regioisomer (7 g, 30.5 mmol) in THF (100 mL) at 0 °C was added NaH (60% in mineral oil, 2.5 g, 61.04 mmol) portionwise. The mixture was then stirred at 0 °C for 30 minutes. Mel (2.85 mL, 45.78 mmol) was added, stirring was continued at room temperature for 16 h. The reaction mixture was quenched with sat. NH4C1 solution (50 mL) and extracted with ethyl acetate (2x50 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO i and concentrated under reduced pressure to afford 4-(methoxymethyl)-l-((2-(trime- thylsilyl) ethoxy) methyl)- IH-imidazole and the corresponding SEM regioisomer. Yield: 6.2 g (crude). LCMS m / z = 243 [M+H]+. Step 3: To a solution of 4-(methoxymethyl)-l -((2 -(trimethylsilyl) ethoxy) methyl)-lH-imidazole and the corresponding SEM regioisomer (3 g, 12.38 mmol) in acetonitrile (35 mL) were added 3-chloro-4-fluorobenzaldehyde (2 g, 12.38 mmol) and diisopropylcarbamic chloride (2 g, 12.38 mmol) followed by DIPEA (6.5 mL, 37.13 mmol) at room temperature and the resulting reaction mixture was heated to 80 °C for 16 h. The reaction mixture was concentrated. The obtained residue was diluted with ethyl acetate (50 mL), washed with water (50 mL) followed by brine (40 mL). The organic layer was dried over anhydrous NaiSCL and concentrated under reduced pressure to afford the cmde product which was purified by column chromatography (SiC 15-20% EtOAc / hex) to afford (3 -chloro-4-fluorophenyl)(4-(methoxymethyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate and the corresponding SEM regioisomer. Yield: 49% (3.2 g). LCMS m / z = 528 [M+H]+.

[0580] Step 4: To a stirred solution of (3-chloro-4-fluorophenyl)(4-(methoxymethyl)-l-((2-(trimethylsilyl)ethoxy)me- thyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and the corresponding SEM regioisomer (3 g, 5.67 mmol) in ACN (50 mL) was added NIS (5.1 g, 22.68 mmol) at room temperature. The reaction mixture was stirred at 80 °C for 6 h followed by stirring at room temperature for 16 h. The reaction mixture was concentrated, the obtained residue was quenched with sodium thiosulfate solution (50 mL) and extracted with DCM (2 x 30 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous Na2SC>4, filtered and concentrated to get the crude product which was purified by column chromatography (SiCK 15-20% EtOAc / hex) to afford (3- chloro-4-fluorophenyl)(5-iodo-4-(methoxymethyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)me- thyl diisopropylcarbamate and the corresponding SEM regioisomer. Yield: 43% (1.6 g). LCMS m / z = 654 [M+H]+.

[0581] Step 5: A stirred solution of (3-chloro-4-fluorophenyl)(5-iodo-4-(methoxymethyl)-l-((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate and the corresponding SEM regioisomer (5 g, 7.633 mmol) in 1,4-dioxane (75 mL) was degassed with argon for 10 minutes followed by the addition of benzyl mer- captan (1.8 mL, 15.266 mmol), DIPEA (4.0 mL, 22.90 mmol), Xantphos (0.670 g, 1.145 mmol) andPd2(dba)s (0.7 g, 0.763 mmol) at room temperature. The reaction mixture was heated to 110 °C for 16 h in a sealed tube. The reaction mixture was filtered and the filtrate was concentrated. The obtained residue was diluted with water (90 mL) and extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with brine (100 mL), dried over ISfeSCL and concentrated under reduced pressure to afford the crude product, which was purified by flash column chromatography ( iCK 50% EtOAc / hex) to yield the title compounds. Yield: 71% (3.5 g). LCMS m / z =650 [M+H]+.

[0582] Intermediate 109

[0583] 5-methyl-4-((methylthio)methyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- IH-imidazoleand the corresponding SEM regioisomer

[0584] Step-1: To a solution of (5-methyl-lH-imidazol-4-yl)methanol(10 g, 89.18 mmol, 1.0 equiv.) in dimethylforma- mide (50 mL) were added DIPEA (46.6 mL, 267.55 mmol, 3.0 equiv.) and SEM-C1 (17.7 mL, 133.77 mmol, 1.5 equiv.) at 0 °C and stirred at RT for 6 h. Reaction mixture was concentrated, diluted with water (150 mL), extracted with ethyl acetate (300 mL). The organic layer was washed with brine (100 mL), dried over sodium sulfate and concentrated under reduced pressure to afford crude product which was purified by column chromatography to afford (5-methyl-l-{[2-(trimethylsilyl)ethoxy]methyl}-lH-imidazol-4-yl)methanol. Yield: 30% (6.5 g, 26.85 mmol). LC-MS: m / z [M+H]+= 243.24.

[0585] Step-2: To a solution of (5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-4-yl)methanol (3 g, 12.38 mmol, 1.0 equiv.) in DCM (50 mL) was added SOCk (4.5 mL, 61.88 mmol, 5.0 equiv.) at 0 °C and stirred at RT for 2 h. The reaction mixture was quenched with water (100 mL) and extracted with ethyl acetate (200 mL). Organic layer was washed with brine (100 mL), dried over sodium sulphate and concentrated under reduced pressure to get 4-(chloromethyl)-5-methyl-l-{[2-(trimethylsilyl)ethoxy]methyl}-lH-imidazole which was directly used in the next step. Yield:2.5 g (crude).

[0586] Step-3: To a solution of the product of step 1 in THF (50 mL) was added triethylamine (4.1 mL), NaSMe (3.4 g, 47.92 mmol, 5.0 equiv.) and stirred at RT for 16 h. The reaction mixture was quenched with water (100 mL) and extracted in ethyl acetate (150 mL). The organic layer was washed with brine (100 mL), dried over sodium sulphate and concentrated under reduced pressure to get crude product which was purified by flash column chromatography to afford 5-methyl-4-[(methylsulfanyl)methyl]-l-{[2-(trimethylsilyl)ethoxy]methyl}-lH-imidazole. Yield: 500 mg, 1.83 mmol. LC-MS: m / z [M+H]+= 273.3.

[0587] Intermediate 110

[0588] (3 -chloro-4-fluorophenyl)(5-methyl-4-((methylsulfonyl)methyl)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- IH-imid- azol-2-yl)methyl diisopropylcarbamate and the corresponding SEM regioisomer

[0589] Step-1: To a mixture of 5-methyl-4-[(methylsulfanyl)methyl]-l-{[2-(trimethylsilyl)ethoxy]methyl}-lH-imidazole (intermediate 109, 500 mg, 1.84 mmol, 1.0 equiv.) and 3-chloro-4-fluorobenzaldehyde (436 mg, 2.75 mmol, 1.5 equiv.) in THF (20 mL) were added N,N-bis(propan-2-yl)carbamoyl chloride (900 mg, 5.51 mmol, 3.0 equiv.), and K2CO3 (703 mg, 3.67 mmol, 2.0 equiv.) at RT and stirred at 80 °C for 16 h. The reaction mixture was concentrated under reduced pressure and the residue was diluted with ethyl acetate (100 mL). Organic part was washed with water (100 mL), brine (75 mL, dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude product which was purified by column chromatography to get (3-chloro-4-fluorophenyl)({5-methyl- 4-[(methylsulfanyl)methyl]-l-{[2-(trimethylsilyl)ethoxy]methyl}-lH-imidazol-2-yl})methyl N,N-bis(propan-2- yl)carbamate. Yield: 34% (350 mg, 0.627 mmol). LC-MS: m / z [M+H]+= 273.3.

[0590] Step-2: To a solution of (3-chloro-4-fluorophenyl)(5-methyl-4-((methylsulfonyl)methyl)-l-((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl diisopropylcarbamate (375 mg, 0.67 mmol, 1.0 equiv.) in DCM (10 mL) was added mCPBA ( 120 mg, 0.67 mmol, 1.0 equiv., 77%) and stirred at RT for 16 h. Reaction mixture was quenched with saturated NaHCO, solution and extracted with DCM (100 mL). Organic layer was dried over magnesium sulfate and concentrated under reduced pressure to (3-chloro-4-fluorophenyl)(5-methyl-4-((methyl- sulfonyl)methyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl which was used in next step. Yield:300 mg (crude). LC-MS: m / z [M+H]+= 590.3.

[0591] Example 1

[0592] 2-((3-chloro-4-fluorophenyl)(methoxy)methyl)-4-(methylsulfonyl)-lH-imidazole

[0593] Step 1: Sodium hydride (60% dispersion in mineral oil, 41 mg, 1.035 mmol) was added to a stirred solution of intermediate 5 (300 mg, 0.690 mmol) in dimethylformamide (10 mL) at 0 °C and the mixture was stirred for 30 min. After 30 minutes, iodomethane (0.13 mL, 2.069 mmol) was added and the reaction mixture was stirred for 1 h at 0 °C. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL x 2). The combined organic layers were dried over Na2SC>4 and concentrated under reduced pressure to get the crude product, which was used in the next step without any further purification.

[0594] Step 2: The cmde product from step 1 (330 mg, cmde) was dissolved in 4M HO in 1,4-dioxane (15 mL) at rt and the mixture was stirred for 18 h. The mixture was concentrated under reduced pressure to get the crude compound, which was purified by prep. HPLC to afford the title compound (36 mg, 15% over two steps).1H-NMR (400 MHz, DMSO-de): 13.10 (s, 1H), 7.81 (s, 1H), 7.66 (dd, 1H), 7.44-7.40 (m, 2H), 5.50 (s, 1H), 3.31 (s, 3H), 3.07 (s, 3H). LCMS m / z = 319 [M+H]+.

[0595] Example 2

[0596] 2-((3-chloro-4-fluorophenyl)(isopropoxy)methyl)-4-(methylsulfonyl)-lH-imidazole p-Toluenesulfonic acid monohydrate (187.3 mg, 0.985 mmol) was added to a stirred solution of (3-chloro-4-flu- orophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methanol (intermediate 6, 100 mg, 0.328 mmol) andNa2SC>4 (50 mg) in propan-2 -ol (10 mL) at rt. The mixture was then heated to 120 °C for 18 h. After cooling to rt, the mixture was concentrated under reduced pressure to get the crude product, which was purified by prep. HPLC to afford the title compound (40 mg, 35%). 'H-NMR (400 MHz, DMSO-d6): 12.97 (s, 1H), 7.80 (s, 1H), 7.64 (d, 1H), 7.42 (dd, 1H), 5.70 (s, 1H), 3.61-3.56 (m, 1H), 3.07 (s, 3H), 1.12 (d, 6H). LCMS m / z = 347 [M+H]+. Example 3

[0597] 2-((3-chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-4-(methylsulfonyl)-lH-imidazole p-Toluenesulfonic acid monohydrate (280.9 mg, 1.477 mmol) was addded to a stirred solution of (3-chloro-4- fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methanol (intermediate 6, 150 mg, 0.492 mmol), cyclohexanol (0.26 mL, 2.461 mmol) and sodium sulfate (50 mg) in toluene (10 mL) at rt. The mixture was then heated to 120 °C for 4 h. The mixture was then concentrated under reduced pressure to get the crude compound, which was purified by prep. HPLC to afford the title compound (30 mg, 15%).'H-NMR (400 MHz, DMSO-ds): 12.95 (s, 1H), 7.80 (s, 1H), 7.66 (d, 1H), 7.42 (d, 2H), 5.75 (s, 1H), 1.85-1.82 (m, 2H), 1.66-1.64 (m, 2H), 1.45-1.44 (m, 1H), 1.33-1.30 (m, 6H), 1.20-1.16 (m, 3H). LCMS m / z = 387 [M+H]+.

[0598] Examples 4-6.

[0599] The title compounds were prepared from the appropriate alcohol using an analogous method to that described for Example 3. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0600] Example 7

[0601] 2-((3-chloro-4-fluorophenyl)(phenoxy)methyl)-4-(methylsulfonyl)-lH-imidazole

[0602] Step 1: To a stirred solution of intermediate 5 (0.200 g, 0.460 mmol) and phenol (0.064 g, 0.690 mmol) in THF (10 mL) at 0 °C were added diethyl azodicarboxylate (0.108 mL, 0.690 mmol) and triphenylphosphine (0.180 g, 0.690 mmol). The reaction mixture was stirred at rt for 3 h. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were dried over anhydrous Na2SC>4 and concentrated under reduced pressure to yield the crude product, which was purified by flash chromatography (SiCK 20-30% EtOAc / PE) to yield the product (0.140 g, 60%).

[0603] Step 2: The product from step 1 (0.120 g, 0.235 mmol) was dissolved in HO (4N) in 1,4-dioxane (2.0 mL) at rt and the mixture was stirred for 4 h. The reaction mixture was then basified with aqueous NaHC'CL and extracted with ethyl acetate (2 x 30 mL). The combined organic layers were dried over anhydrous Na2SC>4 and concentrated under reduced pressure. The residue was purified by flash chromatography (SiCL. 50% EtOAc / PE) to afford the title compound (0.030 g, 34%).1H-NMR (400 MHz, DMSO-d6): 13.29 (s, 1H), 7.89 (s, 1H), 7.81 (dd, 1H), 7.59 - 7.55 (m, 1H), 7.46 (t, 1H), 7.30 - 7.26 (m, 2H), 7.05 (d, 2H), 6.98 (t, 1H), 6.67 (s, 1H), 3.09 (s, 3H). LCMS m / z = 381 [M+H]+.

[0604] Example 8

[0605] 2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-4-(methylsulfonyl)-lH-imidazole

[0606] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 7. Yield: 11 mg, 17%, 'H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 13.29 (s, 1H), 7.90 (s, 1H), 7.80 (dd, J = 7.2 Hz, J = 2.0 Hz, 1H), 7.55-7.53 (m, 1H), 7.45 (t, J = 8.8 Hz), 7.14-7.05 (m, 4H), 6.63 (s, 1H), 5.77 (s, 1H), 3.08 (s, 3H). LCMS m / z = 399 [M+H]+.

[0607] Example 9-10

[0608] 2-((3-chloro-4-fluorophenyl)(4-fluoro-2-methoxyphenoxy)methyl)-5-(methylsulfonyl)-lH-imidazole

[0609] Step 1: To a stirred solution of intermediate 5 (300 mg, 0.690 mmol, 1.0 equiv.) and 4-fluoro-2-methoxyphenol (0.12 mL, 1.5 equiv.) in Toluene (10 mL) at 0 °C were added l,l'-( Azodicarbonyl) dipiperidine, 97% (522 mg, 2.1 mmol.) and tributylphosphine (0.5 mL) sequentially under argon. Resulting reaction mixture was stirred at rt for 16 h. The progress of reaction was monitored by LC-MS. Reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3 ^30 mL). The combined organic layer was washed with brine (20 mL), dried over Na2SC>4 and concentrated under vacuum. The crude product was purified by Normal phase column chromatography.

[0610] Step 2: The product from step 1 was dissolved in HC1 (4N) in 1,4-dioxane (10 mL) at 0 °C. Resulting reaction mixture was stirred at rt for 4 h. The reaction mixture was concentrated under vacuum, basified with NaHCO, solution (pH~9) at 0 °C and extracted with ethyl acetate (3 x15 mL). The combined organic layers were dried over anhydrous Na2SO4and concentrated under reduced pressure. The crude product was purified by prep-HPLC to afford racemic compound (0.030 g, 34%) followed by chiral SFC to yield the title compound as individual enantiomers.

[0611] 400 MHz, DMSO-d6, 25 °C): 5: 13.24 (s, 1H), 7.88 (s, 1H), 7.76 (dd, J = 7.2 Hz, 2.0 Hz, 1H), 7.52-7.48 (m, 1H), 7.46-7.42 (m, 1H), 6.97-6.92 (m, 2H), 6.62 (td, J = 8.8 Hz, 3.2 Hz, 1H), 6.44 (s, 1H), 3.80 (s, 3H), 3.08 (m, 3H). LCMS m / z = 429.16 [M+H]+. Chiral SFC: column: (R,R)Whelk -01 (250 x 4.6) 5p; co-solvent: MeOH, flow: 3 g / min; % of co-solvent: 20%; P = 150 bar, T: 30 °C; 9: Rt = 2.11 min (first eluting); 10: Rt = 2.38 min (second eluting).

[0612] Example 11

[0613] 2-((3 -chloro-4-fluorophenyl)(3 -methoxypheno xy )methy l)-4-methyl-5-(methylsulfony 1)- IH-imidazole Step-1: To a stirred solution of Intermediate 28 (100 mg, 0.23mmol, 1.0 equiv.) in toluene (4 mL) was added triphenyl phosphine (91mg, 0.35mmol,1.5 equiv.) at 0 °C and stirred for 15 min followed by addition of 3-meth- oxyphenol (2 equiv.) and Diisopropyl azodicarboxylate (0.06ml, 0.35mmol,1.5 equiv.) and was stirred at 100°C for 16 h. The reaction mixture was monitored by LCMS. The successful reaction mixtures were quenched with water and extracted with ethyl acetate (50 mL). Organic layer was washed with water (10 mL), brine (10 mL) and dried over Na2SO4. Solvent was concentrated under reduced pressure to get crude product which was purified by flash column chromatography on silica gel.

[0614] Step-2: To a stirred solution of the product of step 1 (1 equiv.) in dioxane (5 mL) was added dioxane-HCl (0.5 mL) at 0 °C and the reaction mixture was stirred at the same temperature for 1.5 hours. The reaction was purified by preparative-HPLC. LCMS m / z = 425.2 [M+H]+.

[0615] Examples 12-13

[0616] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 11.

[0617] Example 14

[0618] 2-((3-chloro-4-fluorophenyl)(4-fluoro-2-methylphenoxy)methyl)-4-methyl-5-(methylsulfonyl)-lH-imidazole To a stirred solution of the intermediate 30 (1.0 equiv.) in DCM (4mL) was added alcohols 4-fluoro-2 -methylphenol (5.0 equiv.) at 0°C and stirred for 15 min followed by addition of TFA (6.0 equiv.),), BF3-Et2O (1.5 equiv.) at 0 °C and the reaction mixture was stirred at 80°C for Ihour. The reaction was purified by preparative-HPLC and desired compound was isolated. LCMS m / z = 427.1 [M+H]+.

[0619] Example 15-16

[0620] 2-((3-chloro-4-fluorophenyl)(((cis)-4-methylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0621] To a mixture of Intermediate 27 (0.3 g, 0.521 mmol) and (cis)-4-methylcyclohexan-l-ol (0.297 g, 2.60 mmol, 5.0 equiv.) in THF (3.0 mL) at 0 °C was added boron trifluoride etherate (0.1 mL, 0.8 mmol) followed by the addition of trifluoroacetic acid (0.179 mL, 2.343 mmol). The resulting reaction mixture was heated to 90 °C and stirred for 90 min in sealed tube. The reaction mixture was concentrated under reduced pressure to obtain a residue, which was diluted with ice water (100 mL) and adjusted to pH 7.0 with sodium bicarbonate solution, followed by extraction with ethyl acetate (2x100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get the crude product, which upon purification by GRACE flash chromatography [C18, 12 g, RP column] using acetonitrile and water as an eluent afforded 100 mg of the title compound. The title compound was then separated into individual enantiomers using chiral SFC.

[0622] LCMS m / z = 415 [M+H]+; ' H-NMR (400 MHz, DMSO-de): 5: 12.61 (s, 1H), 7.64 (dd, 1H), 7.45-7.39 (m, 2H), 5.61 (s, 1H), 3.53-3.51 (m, 1H), 3.04 (s, 3H), 2.37 (s, 3H), 1.82-1.75 (m, 2H), 1.44-137 (m, 5H), 1.31-122 (m, 2H), 0.86 (d, 1H). Chiral SFC: column: Chiralpak IC (4.6 x 150 mm) 5 pm; co-solvent: 0.5% iPrNH2 in iPrOH, flow: 3 mL / min; % of co-solvent: 20%; ABPR: 1500 psi T: 30 °C; 15: Rt = 4.62 min (first eluting); 16: Rt = 8.06 min (second eluting).

[0623] Examples 17-18

[0624] 2-((3-chloro-4-fluorophenyl)(((trans)-4-methylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imi- dazole

[0625] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 15-16. LCMS m / z = 415.3 [M+H]+; 'H-NMR (400 MHz, DMSO-d6): 5: 12.61 (s, 1H), 7.64 (dd, 1H), 7.43-7.38 (m, 2H), 5.68 (s, 1H), 3.27-3.21 (m, 1H), 3.03 (s, 3H), 2.37 (s, 3H), 1.99-193 (m, 2H), 1.65-1.62 (m, 2H), 1.34-1.18 (m, 3H), 0.91- 0.86 (m, 5H). Chiral SFC: column: (R,R) WHELK-01 (4.6 x 150 mm) 3.5 pm; co-solvent: MeOH, flow: 3 mL / min; % of co-solvent: 10%; ABPR: 1500 psi T: 30 °C; 17: Rt = 4.91 min (first eluting); 18: Rt = 6.23 min (second eluting).

[0626] Example 19-20

[0627] 2-((3 -chloro-4-fluorophenyl)(( 1 -methylcyclo hexyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole

[0628] Step 1: To a solution of Intermediate 27 (0.2 g, 0.347 mmol, 1.0 equiv.) and 1-methylcyclohexan-l-ol (10.0 equiv.) in THF (2.0 mL) at rt under N2gas was added boron trifluoride diethyl etherate (0.5 mmol, 1.5 equiv.) and followed by trifluoroacetic acid (0.12 mL, 1.562 mmol, 4.5 equiv.). The resulting reaction mixture was maintained under stirring at 90 °C for 30 min. The reaction was monitored by LC-MS. The reaction mixture was diluted with ice water (25 mL) and adjusted the pH-8.0 with NaHCCh solution and extracted with dichloromethane (2^50 mL). The combined extracts were washed with brine (25 mL), dried over anhydrous Na2SO i and filtered, the filtrate was concentrated under reduced pressure to get 0.28 g of cmde product.

[0629] Step 2: (0.19 g, 0.349 mmol, 1.0 equiv.) and tetra-n-butylammonium fluoride, IM soln, in THF (1.75 mL) in THF (1.9 mL) was stirred at 90 °C for 1 h. The reaction mixture was diluted with ice water (50 mL) and extracted with dichloromethane (2x50 mL). The combined extracts were washed with brine (25 mL), dried over anhydrous Na2SO4and filtered. The filtrate was concentrated under reduced pressure to get the crude product. The crude product was purified by prep-HPLC to give 85 mg (58%) and followed by chiral SFC to yield the title compound as individual enantiomers.

[0630] LCMS m / z = 413.15 [M+H]+. Chiral SFC: column: (R,R)Whelk -01 (250 x 4.6) 5p; co-solvent: isopropanol, flow: 3 mL / min; % of co-solvent: 15%; P = 150 bar, T: 30 °C; 19: Rt = 9.15 min (first eluting); 20: Rt = 11.39 min (second eluting).

[0631] Example 21

[0632] 2-((benzyloxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole To a solution of the Intermediate 31 (80 mg, 0.15mmol, 1.0 equiv.) inDCE (4 mL) were added FeCL (1 mg) and benylic alcohol (5 equiv.) at 0 °C and was stirred at 85°C for 17 h. Thel reaction was purified by preparative- HPLC to yield the desired compound. LCMS m / z = 409.1 [M+H]+.

[0633] Examples 22-23

[0634] The title compounds were prepared from the appropriate alcohol using an analogous method to that described for Example 21.

[0635] Example 24

[0636] 2-((3-chloro-4-fluorophenyl)(((2S,3S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)oxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole

[0637] To a solution of the Intermediate 31 (80 mg, 0.15mmol, 1.0 equiv.) in DCM (4mL) was added 2,6,6-trimethylbi- cyclo[3.1.1]heptan-3-ol (5.0 equiv.) at 0°C and stirred for 15 min followed by addition of TFA (6 equiv.), BF3- Et20 (1.5equiv.) at 0 °C and the reaction mixture was stirred at 70°C for 1 hour. The reaction was purified by preparative-HPLC to yield the desired compound. LCMS m / z = 455.2 [M+H]+.

[0638] Examples 25-28

[0639] The title compounds were prepared from the appropriate alcohol using an analogous method to that described for Example 24.

[0640] Example 29

[0641] 2-((3-chloro-4-fluorophenyl)(cyclobutylmethoxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0642] To a stirred solution of Interemediate 27 (1.0 equiv.) in DCM (4mL) was added cyclobutylmethanol (5.0 equiv.) at 0°C and stirred for 15 min followed by addition of TFA (6.0 equiv.),), BF3-Et2O (1.5 equiv.) at 0 °C and the reaction mixture was stirred at 80°C for Ihour. The reaction was purified by preparative -HPLC to yield the desired compound. LCMS m / z = 387.1 [M+H]+.

[0643] Example 30-34

[0644] The title compounds were prepared from the appropriate alcohol using an analogous method to that described for Example 29. Example 35

[0645] 2-((bicyclo[3.1.0]hexan-3-yloxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0646] Step-1: to a stirred solution of Intermediate 27 (1.0 equiv.) in DCM (4.0mL) was added bicyclo[3.1.0]hexan-3-ol (5.0 equiv.) atO°C and stirred for 15 min followed by addition of TFA (6.0 equiv.) atO °C and the reaction mixture was stirred at 80°C for Ihour. The reaction mixture was quenched with water and extracted with DCM (20 mL). Organic layer was washed with water (4mL), brine (10 mL) and dried over Na2SC>4. Solvent was concentrated under reduced pressure to get crude product which was purified by flash column chromatography on silica gel to get desired compound.

[0647] Step-5: To a stirred solution of the product of Step-1 (1.0 equiv.) in THF (4mL) was added TBAF (3.0 equiv.) at 0°C and the reaction mixture was stirred at 70°C for 2 hours. The reaction was purified by preparative -HPLC to yield the desired compound. LCMS m / z = 397.0 [M-H]+.

[0648] Example 36-39

[0649] The title compounds were prepared from the appropriate alcohol using an analogous method to that described for Example 35.

[0650] Example 40, 41

[0651] 2-((3-chloro-4-fluorophenyl)(l-methylcyclobutoxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0652] Step-1: To a solution of Intermediate 27 (300 mg, 0.521 mmol, 1.0 equiv.), 1-methylcyclobutan-l-ol (180 mg, 2.083 mmol, 4 equiv.) in THF (10 mL) was added boron trifluoride etherate (0.1 mL, 0.781 mmol, 1.5 equiv.) followed by trifluoroacetic acid (0.18 mL, 2.343 mmol, 4.5 equiv.) and was stirred at 60 °C (pre-heated oil bath) for 2 h in a sealed tube. The reaction mixture was diluted with ethyl acetate (50 mL), washed with sat. NaHCCL solution (50 mL), water (50 mL), brine (50 mL) and dried over Na2SO4. Solvent was concentrated under reduced pressure to get crude 2-((3-chloro-4-fluorophenyl)(l-methylcyclobutoxy)methyl)-5-methyl-4-(methylsulfonyl)-l- ((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazole which was used for the next step without further purification. LC-MS m / z [M+H] + = 517.2.

[0653] Step-2: To a solution of the profuct of Step-1 in THF (10 mL) was added 1 M TBAF in THF (6 mL, 5.80 mmol, 10 equiv.) and stirred at 80 °C for 16 h. The reaction mixture was quenched with sat. NH4C1 solution (30 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO i and concentrated under reduced pressure to get the crude product which was purified by reverse phase prep HPLC purification to get racemic 2-((3-chloro-4-fluorophenyl) (1 -methylcyclobutoxy) me- thyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole followed by chiral SFC to yield the title compound as individual enantiomers. LCMS m / z = 387.1 [M+H]+. 'H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 12.58 (bs, 1H), 7.63 (d, J = 7.08 Hz, 1H), 7.40 (d, J = 6.96 Hz, 2H), 5.66 (s, 1H), 3.03 (s, 1H), 2.36 (s, 3H), 2.14-2.03 (m, 2H), 1.81-1.74 (m, 2H), 1.66-1.58 (m, 1H), 1.55-1.48 (m, 1H), 1.27-1.23 (m, 3H). Preparative Chiral SFC: column: (R,R) Whelk -01 (21.1 mm x 250 mm ), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, % of co-solvent: 20%; flow: 100 mL / min; P = 100 bar, T: 35 °C; 40: first eluting enantiomer; 41: second eluting enantiomer.

[0654] Example 42, 43

[0655] 2-((3-chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0656] Step-1: To a stirred solution of (Intermediate 27 (500 mg, 0.87 mmol, 1 equiv.) and cyclohexanol (0.45 mL, 4.34 mmol, 5 equiv.) inTHF (10 mL) was added Boron trifluoride etherate (48%) (0.32 mL, 1.30 mmol, 1.5 equiv.) followed by TFA (0.3 mL, 3.91 mmol, 4.5 equiv.) at room temperature. Resulting solution was stirred at 60 °C for 30 min in sealed tube. After completion of starting material (monitored by LCMS) reaction mixture was quenched with sodium bicarbonate soltion (10 mL) and extracted with ethylacetate (2 x 20 mL). Combined organic layer was washed with water followed by brine (20 mL), dried over Na2SC>4 and concentrated under reduced pressure. Yield: (380 mg, crude). LC-MS m / z [M+H]+= 531.2.

[0657] Step-2: To a stirred solution of the product from Step-1 (380 mg, 0.72 mmol, 1 equiv.) in DCM (1 mL) was added TFA (6 mL) at 0C. Resulting solution was stirred at 800C for 6h. After completion of starting material (monitored by LCMS) reaction mixture was concentrated. Obtained residue was quenched by sodium bicarbonate solution (20 mL) and extracted with ethyl acetate (2 x 20 mL). Combined organic layer was washed with water followed by brine (20 mL), dried over Na2SO4 and concentrated under reduced pressure to afford crude product. Obtained crude product was purified by combi flash column chromatography (silica gel 100-200 mesh, using 60% ethyl acetate in hexane as eluent) to afford the raceme desired product. Yield: 52% over 2 steps (180 mg, 0.45 mmol) followed by chiral SFC to yield the two enantiomers.

[0658] LCMS m / z = 401.2 [M+H]+. 'H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 12.62 (s, 1H), 7.65-7.63 (d, J = 6.92 Hz, 1H), 7.44-7.40 (m, 2H), 5.67 (s, 1H), 3.32 (m, 1H), 3.04 (s, 3H), 2.37 (s, 3H), 1.83 (m, 2H), 1.65 (m, 2H), 1.45 (m, 1H), 1.31 (m, 2H), 1.20-1.18 (m, 3H). Preparative Chiral SFC: column: (R,R) Whelk -01 (21.1 mm x 250 mm ), 5p; co-solvent: isopropanol, %of co-solvent: 30%; flow: 100 mL / min; P = 100 bar, T: 35 °C; 42 (Yield: 91 mg): first eluting enantiomer; 43 (Yield: 77 mg): second eluting enantiomer. Example 44, 45

[0659] 2-((3-chloro-4-fluorophenyl)((3-fluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0660] Step-1: To a solution of Intermediate 27 (250 mg, 0.43 mmol, 1.0 equiv.) and 2-fluorophenyl)methanol (0.1 mL, 0.86 mmol, 2.0 equiv.) in THF (15 mL) were added boron trifluoride etherate (0.08 mL, 0.65 mmol, 1.5 equiv.) and TFA (0.15 mL, 1.95 mmol, 4.5 equiv.) at 0 °C. Reaction mixture was stirred at 60 °C for 1 h in a sealed tube. Reaction mixture was concentrated under reduced pressure, diluted with ice-cold water (20 mL) and neutralised with sat. NaHCCL solution. The aqueous part was extracted with ethyl acetate (2 x 60 mL). The combined organic layers were washed with brine (20 mL), dried over sodium sulfate and concentrated under reduced pressure to get crude 2-((3-chloro-4-fluorophenyl)((2-fluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazole which was used in next step without further purification.

[0661] Step-2: A mixture of crude product from Step-1 and TFA (4 mL) was stirred at 80 °C for 1 h. Reaction mixture was concentrated under reduced pressure, diluted with MeOH (15 mL), Amberlyst A21 resin (100 mg) was added and stirred at RT for 2 h. After filtration, the filtrate was concentrated under reduced pressure to get the crude product which was purified by RP-prep-HPLC to get the racemic final product (80 mg, 0.187 mmol). folio wed by chiral SFC to yield the title compound as individual enantiomers.

[0662] LCMS m / z = 427.2 [M+H]+. ' H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 12.75 (bs, 1H), 7.69-7.67 (m, 1H), 7.51- 7.36 (m, 4H), 7.23-7.17 (m, 2H), 5.76 (s, 1H), 4.56 (s, 2H), 3.05 (s, 3H), 2.36 (s, 3H). Preparative Chiral SFC: column: (R,R) Whelk -01 (21.1 mm x 250 mm ), 5p; co-solvent: isopropanol, % of co-solvent: 40%; flow: 100 mL / min; P = 100 bar, T: 35 °C; 44 (Yield: 35 mg): first eluting enantiomer; 45 (Yield: 34 mg): second eluting enantiomer.

[0663] Example 46-50

[0664] The title compounds were prepared from the intermediates 27 and appropriate reagents using an analogous method to that described for Example 44. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC. Example 51 -methyl-4-(methylsulfonyl)-l H-imidazol-2-yl)methoxy)methyl)pyridine

[0665] Step-1: To a solution of Intermediate 27 (200 mg, 0.346 mmol, 1.0 equiv.), pyridin-2-ylmethanol (0.34 mL, 3.465 mmol, 10.0 equiv.) in DCM (4.0 mL) was added boron trifluoride etherate (0.17 mL, 1.386 mmol, 4 equiv.) followed by trifluoroacetic acid (0.26 mL, 3.465 mmol, 10.0 equiv.) and was stirred at 60 °C in pre-heated oil bath for 3 h. The reaction mixture was quenched with aq. NaHCO3and extracted with ethyl acetate (2 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to get the crude 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazol-2-yl)methoxy)methyl)pyridine which was used for the next step without further purification. LC-MS: m / z [M+H] + = 539.7

[0666] Step-2: A mixture of crude product from Step-1 and TFA (1.0 mL) was stirred at 60 °C for 20 min. The reaction mixture was concentrated under reduced pressure to get the residue, which was dissolved in MeOH (10 mL), Amberlyst-A21 ion exchange resin (500 mg) was added and stirred for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure to get the crude product which was purified by RP-Prep HPLC purification to yield racemic 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)meth- oxy)methyl)pyridine.

[0667] Yield: 11 mg, 6%. LCMS m / z = 410.1 [M+H]+. 'H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 11.60 (brs, 1H), 8.52 (d, J = 4.4 Hz, 1H), 7.82 (t, J = 7.64 Hz, 1H), 7.72 (d, J = 7.0 Hz, 1H), 7.53 (d, J = 7.76 Hz, 1H), 7.46-7.44 (m, 2H), 7.33-7.30 (m, 1H), 5.73 (s, 1H), 4.58 (s, 2H), 3.05 (s, 3H), 2.37 (s, 3H).

[0668] Example 52, 53

[0669] The title compounds were prepared from the intermediates 27 and appropriate reagents using an analogous method to that described for Example 44. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0670]

[0671] Example 54, 55

[0672] 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methoxy)methyl)-5-methylthia-

[0673] Step-1: To a solution of Intermediate 27 250 mg, 0.43 mmol, 1.0 equiv.), (5-methyl-l,3-thiazol-2-yl)metha- nol (280 mg, 2.16 mmol, 5.0 equiv.), in THF (6 mL) was added boron trifluoride etherate (0.1 mL, 0.78 mmol, 1.5 equiv.) followed by trifluoroacetic acid (0.18 mL, 2.34 mmol, 4.5 equiv.) and was heated 60 °C for 90 min in a sealed tube. The reaction mixture was quenched with aq. NaHCCL and extracted with ethyl acetate (2 x 50 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure to get the crude 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methoxy)methyl)-5-methylthiazole, which was used in the next step without further purification. LC-MS: m / z [M+H] + = 559.9.

[0674] Step-2: A mixture of crude product from Step- in TFA (3 mL) was stirred at 80 °C for 15 min in a pre-heated oil bath. The reaction mixture was concentrated under reduced pressure, diluted with MeOH (10 mL), Amberlyst- A21 ion exchange resin (500 mg) was added and stirred for 2 h. After filtration, the filtrate was concentrated under reduced pressure to get the crude product which was purified by RP-prep-HPLC to get racemic compound, followed by chiral SFC to yield the title compound as individual enantiomers.

[0675] 'H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 12.75 (bs, 1H), 7.69-7.67 (m, 1H), 7.51-7.36 (m, 4H), 7.23-7.17 (m, 2H), 5.76 (s, 1H), 4.56 (s, 2H), 3.05 (s, 3H), 2.36 (s, 3H). LCMS m / z = 445.2 [M+H]+. Preparative Chiral SFC: column: (R,R) Whelk -01 (21.1 mm x 250 mm ), 5p; co-solvent: isopropanol, % of co-solvent: 40%; flow: 70 mL / min; P = 100 bar, T: 35 °C; 54 (Yield: 35 mg): first eluting enantiomer; 55 (Yield: 34 mg): second eluting enantiomer.

[0676] Example 56, 57

[0677] 2-((3-chloro-4-fluorophenyl)((3,5-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0678] To a solution of Intermediate 27 (250 mg, 0.43 mmol, 1.0 equiv.) and and (2,6-difluorophenyl)methanol (313 mg, 2.17 mmol, 5.0 equiv.) in DCM (20 mL) were added BF3.Et2O (0.08 mL, 0.65 mmol, 1.5 equiv.) and TFA (0.17 mL, 2.17 mmmol, 5.0 equiv.) at 0 °C and stirred at RT for 16 h. Reaction mixture was concentrated, diluted with ice-cooled water (20 mL), neutralized with sat. NaHCO3solution (50 mL) and extracted with ethyl acetate (150 mL). Organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude product which was purified by reverse phase prep HPLC to afford racemic 2-((3-chloro-4-fluorophenyl)((3,5-difluoroben- zyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole, followed by chiral SFC to yield the title compound as individual enantiomers.

[0679] ' H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 12.75 (bs, 1H), 7.69-7.67 (m, 1H), 7.51-7.36 (m, 4H), 7.23-7.17 (m, 2H), 5.76 (s, 1H), 4.56 (s, 2H), 3.05 (s, 3H), 2.36 (s, 3H). LCMS m / z = 445.2 [M+H]+. Preparative Chiral SFC: column: (R,R) Whelk -01 (21.1 mm x 250 mm ), 5p; co-solvent: isopropanol, % of co-solvent: 40%; flow: 70 mL / min; P = 100 bar, T: 35 °C; 56 (Yield: 35 mg): first eluting enantiomer; 57 (Yield: 34 mg): second eluting enantiomer.

[0680] Example 58-101

[0681] The title compounds were prepared from the intermediates 27 and appropriate reagents using an analogous method to that described for Example 56 / 57. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0682]

[0683] Example 104, 105

[0684] The title compounds were prepared from the intermediates 27 and appropriate reagents using an analogous method to that described for Example 102 / 103. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0685] Example 106, 107

[0686] 2-((3-chloro-4-fluorophenyl)((4-methylbenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole

[0687] Step-1: A mixture of Intermediate 27 (250 mg, 0.43 mmol, 1.0 equiv.) and p-tolylmethanol (265 mg, 2.17 mmol, 5.0 equiv.) in DCM (20 mL) were added BFs.Et^O (0.08 mL, 0.65 mmol, 1.5 equiv.) and TFA (0.17 mL, 2.17 mmmol, 5.0 equiv.) at 0 °C and stirred at RT for 16 h. Reaction mixture was concentrated under reduced pressure, diluted with ice-cooled water (20 mL), neutralized with sat. NaHCCL solution (50 mL) and extracted with ethyl acetate (150 mL). Organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude 2-((3-chloro-4-fluorophenyl)((4-methylbenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)-l-((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazole which was directly used in the next step. LC-MS: m / z [M+H]+= 553.21

[0688] Step-2: To a solution of cmde product from Step-1 in THF (50 mL) was added TBAF solution (5.4 mL, 5.4 mmol, 5.0 equiv., IM in THF) at RT and was stirred at 65 °C for 1 h. Reaction mixture was quenched with sat. NH4C1 solution (50 mL) and extracted with ethyl acetate (150 mL). Organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude product which was purified by reverse phase prep HPLC to get the racemic final product (120 mg), followed by chiral SFC to yield the title compound as individual enantiomers.

[0689] 'H-NMR (400 MHz, DMSO-d6, 25 °C): 5: 12.75 (bs, 1H), 7.67-7.65 (m, 1H), 7.44-7.41 (m, 2H), 7.24-7.23 (m, 2H), 7.17-7.15 (m, 2H), 5.6 (s, 1H), 4.45 (s, 2H), 3.05 (s, 3H), 2.37 (s, 3H), 2.29 (s, 3H). LCMS m / z = 423.2 [M+H]+. Preparative Chiral SFC: column: (R,R) Whelk -01 (21.1 mm x 250 mm), 5p; co-solvent: isopropanol, % of co-solvent: 40%; flow: 70 mL / min; P = 100 bar, T: 35 °C. 106 (Yield: 41 mg): first eluting enantiomer; 107 (Yield: 41 mg): second eluting enantiomer.

[0690] Example 108. 109

[0691] The title compounds were prepared from the intermediates 27 and appropriate reagents using an analogous method to that described for Example 106 / 107. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0692] Example 110-195

[0693] The title compounds were prepared using the following general synthetic methods.

[0694] Synthetic Method (B): to a solution of Intermediate 27 (50.0 mg, 92.57 pmol) and the appropriate reagente / nucle- ophile (5 equivalents) in THF (1 ml) was added trifluoroborane ether complex (131.52 mg, 925.68 pmol, 120.0 pl, 10.0 equiv). The resulting mixture was maintained at 80 °C under stirring for 4h. The reaction progress was monitored by LCMS . After completion of the reaction the reaction mixture was evaporated under reduced pressure. The residue was subjected to prep HPLC.

[0695] Synthetic Method (Bl): to a solution of Intermediate 27 (50.0 mg, 86.78 pmol) and the appropriate reagente / nu- cleophile (5 equivalents) in THF (1 mL) was added trifluoroborane ether complex (61.61 mg, 433.66 pmol, 50.0 pl, 5.0 equiv). The resulting mixture was maintained at 80 °C under stirring for Ih. The reaction progress was

[0696] Ill monitored by LCMS. Upon completion of the reaction the reaction mixture was evaporated under reduced pressure. The residue was subjected to prep HPLC.

[0697] Example 196

[0698] N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-fluoroaniline p-Toluenesulfonic acid monohydrate (0.280 g, 1.477 mmol) was added to a stirred solution of intermediate 6,

[0699] 0.150 g, 0.492 mmol) and 4-fluoroaniline (0.164 g, 1.477 mmol) in toluene (10 mL) at rt and the mixture was then heated to 120 °C for 4 h. After cooling to rt, the reaction mixture was concentrated under reduced pressure to get the crude product which was purified by Prep-HPLC to afford the title compound (0.020 g, 10%).1H-NMR (400 MHz, DMSO-ds): 5: 11.98 (s, 1H), 7.80 (s, 1H), 7.73 (dd, 1H), 7.51 - 7.47 (m, 1H), 7.40 (t, 1H), 6.94 - 6.89 (m, 2H), 6.68 - 6.64 (m, 2H), 6.54 (d, 1H), 5.78 (d, 1H), 3.07 (s, 3H). LCMS m / z = 398 [M+H]+. Example 197-212

[0700] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 196. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC. Example 213, 214

[0701] N-((3 -chloro-4-fluorophenyl)(4-(methylsulfonyl)- lH-imidazol-2-yl)methyl)-4,4-difluorocyclohexan- 1 -amine

[0702] Step 1: To a solution of Intermediate 9 (0.5 g, 1.157 mmol) inDCM (20.0 mL) were added 4, 4-difluorocyclohexan- 1-amine hydrochloride (0.3 g, 1.736 mmol), triethylamine (0.3 mL, 1.736 mmol) and TiC'l i (IM in DCM; 1.75 mL, 0.173 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for 3 h. To this mixture were then added MeOH (10.0 mL) and NaCNBH3(0.15 g, 2.315 mmol) at 0 °C. The reaction mixture was stirred at rt for 16 h. The reaction mixture was neutralized with NaHCO3solution and extracted with ethyl acetate (2 x 80 mL). The combined organic layers were washed with brine, dried over sodium sulphate and concentrated under reduced pressure to get the crude product, which was used for the next step without further purification (0.48 g, 75%). LCMS m / z = 552 [M+H]+.

[0703] Step 2: To a stirred solution of the crude product from step 1 (0.5 g, 0.906 mmol, 1.0 eq.) in DCM (5.0 mL) was added 4(M) HC1 in dioxane (15.0 mL) at 0 °C. The reaction was stirred at rt for 4 h. The reaction mixture was concentrated under reduced pressure to obtain a residue which was neutralized with NaHCO3solution and extracted with ethyl acetate (2x100 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure. The resulting crude product was purified by CombiFlash column chromatography followed by chiral SFC to yield the title compound as individual enantiomers.

[0704] LCMS m / z = 422 [M+H]+.!H NMR (DMSO-d6, 400 MHz, 25 °C): 12.76 (s, 1H), 7.78 (s, 1H), 7.70 (d, 1H), 7.43- 7.36 (m, 2H), 5.07 (s, 1H), 3.05 (s, 3H), 2.91-2.81 (m, 1H), 2.49-2.81 (m, 1H), 2.07-1.85 (m, 2H), 1.81-1.62 (m, 4H), 1.51-1.41 (m, 2H). Chiral SFC: column: ChiralpakIC (4.6 x250 mm) 5 pm; co-solvent: 0.5% isopropylamine in isopropanol, flow: 4 mL / min; % of co-solvent: 40%; ABPR: 100 bar T: 35 °C; 213 (Yield: 85 mg, 22%): first eluting enantiomer. Rt = 2.18 min; 214 (Yield: 80 mg, 20%): second eluting enantiomer Rt = 2.71 min.

[0705] Example 215, 216

[0706] 3-chloro-N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)aniline

[0707] To a solution of intermediate 9a (First eluting regioisomer, 0.25 g, 0.577 mmol) and 3 -chloroaniline (0.074 g, 0.577 mmol) in DCM (10.0 mL) was added triethylamine (0.25 mL, 1.73 mmol) and then TiC'l i (IM in DCM, 0.9 mL, 0.86 mmol) dropwise at 0° C. The reaction mixture was stirred at 0 °C for 3 h, followed by the addition of MeOH (10 mL) and NaCNBH3(0.73 g, 1.15 mmol) at 0 °C. The reaction mixture was stirred at rt for 16 h. The reaction mixture was neutralized with NaHCO;, solution and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by CombiFlash column chromatography (SiO2. 0-60% EtOAc / Hex) followed by SFC to yield the title compound as individual enantiomers.

[0708] LCMS m / z = 413 [M+H]+.1H NMR (DMSO-d6, 400 MHz, 25 °C): 12.72 (s, 1H), 7.74 (s, 1H), 7.54 (d, 1H), 7.37- 7.30 (m, 2H), 7.18-7.14 (m, 2H), 7.04-6.99 (m, 2H), 4.44-4.40 (m, 1 H), 3.48-3.42 (m, 1H), 3.24-3.18 (m, 1H), 3.09 (s, 3H). Chiral SFC: column: Chiralpak IC (4.6 x 250 mm) 5 pm; co-solvent: 0.5% isopropylamine in isopropanol, flow: 4 mL / min; % of co-solvent: 40%; ABPR: 100 bar T: 35 °C; 215 (Yield: 27 mg, 11%): first eluting enantiomer. Rt = 2.33 min; 216 (Yield: 30 mg, 12%): second eluting enantiomer Rt = 2.87 min.

[0709] Examples 217-220

[0710] The title compounds were prepared from the appropriate intermediates (9 and 13) and reagents using an analogous method to that described for Example 215 / 216. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0711] Example 221

[0712] N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-fluoro-N-methylaniline

[0713] Step-1: To a solution of intermediate 9 (0.6 g, 1.386 mmol, 1.0 equiv.) inDCM (20.0 mL) were added 4-fluoroan- iline 4-fluoroaniline (0.231 g, 2.079 mmol, 1.0 equiv.), triethylamine (0.3 mL, 2.079 mmol, 1.5 equiv.) and TiCL (IM in DCM; 2.1 mL 2.079 mmol, 1.5 equiv.) at dropwise at 0° C. Reaction mixture was stirred at 0 °C for 3 h. To these mixture, MeOH (10 mL) and NaCNBH3(0.175 g, 2.772 mmol, 2.0 equiv.) was added at 0 °C. The reaction mixture was stirred at room temperature for 16 h. Reaction mixture was neutralized with NaHCO3solution and extracted with ethyl acetate (2 x 100 mL). Combined organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to get cmde product. Resulting crude was purified by combiflash column chromatograph to yield N-((3-chloro-4-fluorophenyl)(5-(methylsulfonyl)-l-((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-2-yl)methyl)-4-fluoroailine. Yield: 68% (0.5 g, 0.948 mmol). LCMS: m / z [M+H]+= 528.19.

[0714] Step-2: The product from Step-1 (0.25 g, 0.473 mmol, 1.0 equiv.) in methanol (12.0 mL) were added acetic acid (1.5 mL), formaldehyde (37%, 5.0 mL) and sodium cyanoborohydride (0.12 g, 1.894 mmol, 3.0 equiv.) at 0 °C. The reaction mixture was stirred at room temperature for 2 h. Reaction was diluted with ice water and neutralized with NaHCO3solution. Aqueous layer was extracted with ethyl acetate (2 x 100 mL). Combined organic layer was washed with brine and dried over Na3SO i and concentrated under reduced pressure to get N-((3-chloro-4-fluoro- phenyl)(5-(methylsulfonyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)-4-fluoro-N-methyl- aniline which was used for the next step without further purification. LCMS: m / z [M+H]+= 542.2.

[0715] Step-3: To a stirred solution of the crude product from Step-2 in DCM (5.0 mL) was added 4(M) HO in dioxane (15.0 mL) at 0 °C. Reaction was stirred at room temperature for 4 h. Reaction mixture was concentrated under reduced pressure to get residue which was neutralized with NaHCO3solution and extracted with ethyl acetate (2x 100 mL). Combined organic layer was washed with brine, dried over Na3SO i and concentrated under reduced pressure to get crude product. Resulting crude was purified by combiflash column chromatography to yield the title compound. Yield (over 2 steps): 57% (0.11 g, 0.267 mmol). LCMS m / z = 410.2 [M+H]+.!H NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm): 12.99 (s, 1H), 7.87 (s, 1H), 7.47 (d, J= 5.52 Hz, 1H), 7.40 (t, J= 9 Hz, 1H), 7.27-6.24 (m, 1H), 7.04 (t, J= 8.68 Hz, 2H), 6.92-6.89 (m, 2H), 6.27 (s, 1H), 3.08 (s, 3H), 2.69 (s, 3H). Example 222

[0716] 3 -chloro-N-((3 -chloro-4-fluorophenyl)(4-(methylsulfonyl)- lH-imidazol-2-yl)methyl)-N-methylaniline

[0717] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 221 for step 1 and step 2 but with step 3 follows: to a stirred solution of the product of step 2 (0.6 g, 1 equiv.) in dimethylformamide (15.0 mL) was added CsF (0.66 g, 4.0 equiv.) at room temperature. Reaction was stirred at 80 °C for 16 h. Reaction mixture was diluted with ice water and extracted with ethyl acetate (2 x 100 mL). Combined organic layer was washed with brine, dried over sodium sulphate, and concentrated under reduced pressure to get cmde product. Resulting crude was purified by RP prep HPLC to yield the titlae compound.

[0718] LCMS: m / z [M-H]’ = 426.09;!H NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm): 13.01 (s, 1H), 7.90 (s, 1H), 7.46- 7.40 (m, 2H), 7.25-7.24 (m, 1H), 7.20 (t, J= 8.16 Hz, 1H), 6.90 (s, 1H), 6.85-6.82 (m, 1H), 6.74 (d, J= 7.76 Hz, 1H), 6.44, (s, 1H), 3.09 (s, 3H), 2.75 (s, 3H).

[0719] Example 223, 224

[0720] 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3-methoxypyri- din-2-amine

[0721] Step 1: To a solution of Intermediate 27 (0.300 g, 0.521 mmol) in THF (15 mL) was added 5-chloro-3-methoxy- pyridin-2-amine (0.413 g, 2.603 mmol) followed by boron trifluoride etherate (0.111 g, 0.781 mmol) and trifluoroacetic acid (0.267 g, 2.343 mmol) at ambient temperature. The resulting mixture was heated to 80 °C for 1 h. The mixture was concentrated under reduced pressure to get the crudecresidue, which was diluted with sat. NaHCO3solution (20 mL) and extracted with ethyl acetate (2^20 mL). The combined organic layers were washed with water (20 mL), dried over anhydrous Na2SO i. filtered, concentrated under reduced pressure and purified by flash chromatography.

[0722] Step 2: The product from Step 1 (0.230 g, 0.390 mmol) in THF (11.5 mL), was added tetra butyl ammonium fluoride (IM solution in THF, 1.951 mL, 1.951 mmol) at ambient temperature. The resulting mixture was heated to 90 °C for 1 h. The mixture was concentrated under reduced pressure to obtain a residue, which was diluted with sat. NaHCO3solution (20 mL) and extracted with ethyl acetate (2x20 mL). The combined organic layers were washed with water (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to obtaine the crude compound, which upon purification by flash chromatography (C18, 12 g column, using acetonitrile and water as an eluent) afforded 55 mg (36%) of the title compound. The title compound was then separated into individual enantiomers using chiral SFC.

[0723] 'H-NMR (400 MHz, DMSO-de): 5: 12.62 (s, 1H), 7.62-7.59 (m, 2H), 7.39-7.33 (m, 2H), 7.21 (d, 1H), 6.89 (d, 1H), 6.34 (d, 1H), 3.88 (s, 3H), 3.05 (s, 3H), 2.37 (s, 3H). LCMS m / z = 459 [M+H]+. Chiral SFC: column: Chiralpak IG (4.6 x 150 mm) 5 pm; co-solvent: 0.5% DEA in MeOH, flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1500 psi T: 30 °C; 223: first eluting enantiomer. Rt = 1.44 min; 224: second eluting enantiomer Rt = 1.87 min.

[0724] Examples 225-230

[0725] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 223-224. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0726] Example 231. 232

[0727] N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)pyridin-2 -amine

[0728] Step 1: To a stirred solution of Intermediate 27 (300 mg, 0.521 mmol) in THF (10 mL) was added pyridin-2 -amine (245.013 mg, 2.603 mmol) followed by boron trifluoride etherate (0.097 mL, 0.781 mmol) and trifluoroacetic acid (0.191 mL, 2.343 mmol), The reaction mixture was heated to 100 °C for 2 h. The reaction mixture was concentrated under reduced pressure and the residue was neutralized with saturated NaHC'CL solution (10 mL) and extracted with ethyl acetate (2^50 mL). The combined organic layers were dried over anhydrous Na SO i. filtered and concentrated under reduced pressure to obtain the crude compound, which upon purification by flash chromatography (C18, 24 g cartridge, eluted with 0.1% formic acid and acetonitrile), afforded 150 mg (55%) of the desired intermediate.

[0729] Step 2: To a stirred solution of the isolated intermediate in 1,4-dioxane (5 mL) was added 4M HO in 1,4-dioxane (2 mL) at 0 °C and the mixture was stirred at ambient temperature for 16 h. The mixture was concentrated under reduced pressure and the residue was triturated with diethyl ether (20 mL), decanted and dried. The obtained material was purifyed by prep-HPLC to yield 60 mg (53%) of the title compound. The title compound was then separated into individual enantiomers using chiral SFC.

[0730] LCMS m / z = 395 [M+H]+; ’H-NMR (400 MHz, DMSO-de): 5: 12.68 (s, 1H), 7.95 (dd, 1H), 7.63 (dd, 1H), 7.51 (d, 1H), 7.44-7.35 (m, 3H), 6.70 (d, 1H), 6.56-6.53 (m, 1H), 6.34 (d, 1H), 3.03 (s, 3H), 2.37 (s, 3H). Chiral SFC: column: Chiralpak AS-3 (4.6 x 150 mm) 3 pm; co-solvent: 0.5% DEA in MeOH, flow: 3 mL / min; % of co-solvent: 10%; AB PR: 1500 psi T: 30 °C; 231: first eluting enantiomer. Rt = 2.12 min; 232: second eluting enantiomer Rt = 2.75 min.

[0731] Examples 233-239

[0732] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for example 231-232. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0733] Example 240-241

[0734] 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)pyrimidin-2- amine

[0735] Step 1: To a stirred solution of Interemediate 27 (250 mg, 0.434 mmol, 1.0 equiv.) and 5-chloropyrimidin-2 -amine (281 mg, 2.17 mmol, 5.0 equiv.) in DCM (20.0 mL) were added boron trifluoride etherate (0.08 mL, 0.65 mmol, 1.5 equiv.) and TFA (0.149 mL, 1.952 mmol, 4.5 equiv.) and was stirred at rt for Ih min. Reaction mixture was diluted with ice-cold water (50 mL) and extracted with DCM (2 x 50 mL). Combined organic layers were washed with sat. NaHCCL solution (50 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to get crude product which was used in the next step without further purification. LC-MS: m / z [M+H]+= 560.0

[0736] Step 2: To a stirred solution of the product of Stepl, in TFA (4.5 mL) was heated at 60 °C for 20 min. Reaction mixture concentrated under reduce pressure to get crude product which was diluted with MeOH (15.0 mL), Am- berlyst A21 (500 mg) resin was added to and stirred at RT for 2 h. Reaction mixture was filtered, washed with MeOH (10.0 mL) and the filtrate was concentrated under reduced pressure to get crude product which was purified by reverse phase prep HPLC to afford racemif title compound. The title compound was then separated into individual enantiomers using chiral SFC. LCMS m / z = 430.1 [M+H]+; ’H-NMR (400 MHz, DMSO-de): 5: 12.62 (br s, 1H), 8.40 (s, 2H), 8.35-8.33 (m, 1H), 7.67-7.65 (m, 1H), 7.45-7.36 (m, 2H), 6.25-6.23 (m, 1H), 3.02 (s, 3H), 2.36 (s, 3H). Preparative chiral SFC: column: I Cellulose C (21.1 mmx250 mm), 5p; co-solvent: MeOH, flow: 70 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C; 240 (Yield: 17 mg): first eluting enantiomer. 241 (Yield: 17 mg): second eluting enantiomer.

[0737] Examples 242-249

[0738] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for example 240-241. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0739] Example 250, 251

[0740] N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)benzo[d]thiazol-2 -amine

[0741] A solution of Interemediate 27 (0.300 g, 0.521 mmol, 1 equiv.) in THF (15 mL) were added benzo [d]thiazol-2- amine (0.391 g, 2.603 mmol, 5 equiv.) followed by boron trifluoride etherate (0.111 g, 0.781 mmol, 1.5 equiv.), trifluoroacetic acid (0.267 g, 2.343 mmol, 4.5 equiv.) at RT. Then reaction mixture was stirred at 100 °C for 1 h. After completion of reaction as judged by LC-MS, the reaction mixture was concentrated under reduced pressure to get the residue, which was diluted with sat. NaHCO, solution (20 mL) and extracted with ethyl acetate (2x20 mL). Combined organic layers were washed with water (20 mL), dried over ISfeSCL, filtered and concentrated under reduced pressure to obtained crude compound, which upon purification by flash chromatography (C18, 12 g column, using acetonitrile and water as an eluent), followed by prep-HPLC furnished 100 mg the racemic material. Further separation y SFC.

[0742] LCMS m / z = 451.2 [M+H]+. Chiral SFC: column: Chiralcel OJ-H (4.6 x 250 mm) 5 pm; co-solvent: MeOH; flow: 3 mL / min; % of co-solvent: 35%; P = 100 bar, T: 30 °C; 250 (Yield: 25 mg): first eluting enantiomer. Rt = 2.48 min; 251 (Yield: 25 mg): second eluting enantiomer Rt = 4.31 min.

[0743] Examples 252-258

[0744] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described fo example 250-251. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0745] Example 259, 260

[0746] 4,5-dichloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)pyridin-2- amine

[0747] To a solution of of Intermediate 27 (300 mg, 0.521 mmol) inTHF (10 mL) was added4,5-dichloropyridin-2-amine (169.7mg, 1.04 mmol) followed by boron trifluoride etherate (0.8 mmol) and trifluoroacetic acid (0.2 mL, 2.3 mmol, 4.5 equiv.) at ambient temperatture. The mixture was heated to 80 °C for 4 h. The mixture was concentrated under reduced pressure to get the crude compound, which upon purification by flash chromatography (C18, 12 g column, using 0.1% formic acid in water and acetonitrile as an eluent) furnished 120 mg (50%) as the title compound. The title compound was then separated into individual stereoisomers using chiral SFC.

[0748] LCMS m / z = 463 [M+H]+; ' H-NMR (400 MHz, DMSO-de): 5: 12.72 (br s, 1H), 8.12 (s, 1H), 8.01 (d, 1H), 7.61 (d, J= 1H), 7.43-7.38 (m, 2H), 6.98 (s, 1H), 6.27 (d, 1H), 3.03 (s, 3H), 2.36 (s, 3H). Chiral SFC: column: Chiracel OJ-H (4.6 x 250 mm) 5 pm; co-solvent: MeOH, flow: 3 mL / min; % of co-solvent: 15%; ABPR: 1500 psi T: 30 °C; 259: first eluting enantiomer. Rt = 7.16 min; 260: second eluting enantiomer Rt = 10.79 min.

[0749] Examples 261-292

[0750] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for 259-260. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC.

[0751] Example 292, 293

[0752] N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-fluoro-6-methylpyridin-

[0753] 2-amine

[0754] To a solution of of Intermediate 27 (300 mg, 0.521 mmol) and 5-fluoro-6-methylpyridin-2 -amine (0.32 g, 2.599 mmol, 5 equiv.) in DCM (10 mL) were added BFs-ELO (0.2 ml, 0.78 mmol, 3 equiv.) and TFA (0.4 ml, 2.33 mmol, 9 equiv.) at 0 °C and stirred at RT for 16 h. Reaction mixture was concentrated under reduced pressure, diluted with ice-cooled water (20 mL), neutralized with sat. NaHCCL solution (50 mL) and extracted in ethyl acetate (150 mL). Organic layer was dried over sodium sulfate and concentrated under reduced pressure to get crude product which was purified by reverse phase prep HPLC to afford the racemic title compound. Yield: 40.5% (90 mg, 0.21 mmol). The title compound was then separated into individual stereoisomers using chiral SFC.

[0755] LCMS m / z = 427.2 [M+H]+;1H-NMR (400 MHz, DMSO-d6): 12.65 (s, 1H), 7.65-7.63 (s, 1H), 7.44-7.28 (m, 4H), 6.54-6.51 (d, J=2.8 Hz, 1H), 6.25-6.23 (d, J=8.4 Hz, 1H), 3.04 (s, 3H), 2.36 (s, 3H), 2.20 (s, 3H). Preparateive chiral SFC: column: ((21.1 mm x 250mm ), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 60 mL / min; % of co-solvent: 20%; ABPR: 120bar T: 35°C; 292 (Yield: 31 mg) first eluting enantiomer. 293 (Yield: 27 mg): second eluting enantiomer.

[0756] Examples 294-297

[0757] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for 292-293. Chiral compounds can be separated after synthesis using chiral SFC or chiral HPLC. Example 298

[0758] 5-bromo-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)thiazol-2 -amine

[0759] Step 1: To a stirred solution of Intermediate 27 (1 g, 1.736 mmol) in THF (10 mL) were added thiazol-2-amine (868.99 mg, 8.678 mmol), BF3-Et2O (367.06 mg, 2.603 mmol) and trifluoroacetic acid (890.47 mg, 7.810 mmol) and the reaction mixture was heated to 100 °C for 1 h. The mixture was concentrated under reduced pressure and the residue was neutralized with saturated NaHCCh solution (50 mL), then extracted with ethyl acetate (2x200 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous NaiSO i. filtered and concentrated under reduced pressure to obtain the crude compound, which upon purification by flash chromatography (C18, 40 g cartridge, eluting with 0.1% formic acid and acetonitrile) afforded 200 mg (21%) of the substitued intermediate. LCMS m / z = 529 [M-H]-

[0760] Step 2: To a stirred solution of N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)thiazol-2-amine (150 mg, 0.282 mmol) in dimethylformamide (3 mL) was added N-bromosuccinimide (50.2 mg, 0.28 mmol) at ambient temperature and the mixture was stirred for 2 h. The mixture was diluted with water (20 mL) and extracted with ethyl acetate (2x100 mL). The combined organic layers were washed with brine (30 mL), dried over anhydrous NibSO i. filtered and concentrated under reduced pressure to obtain the crude compound, which upon purification by flash chromatography (C18, 12 g cartridge, eluting with 0.1% formic acid and acetonitrile) yielded 100 mg (58%) of 5-bromo-N-((3-chloro-4-fluor- ophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)thiazol-2- amine. LCMS m / z = 609 [M+H]+

[0761] Step 3: To a stirred solution of 5-bromo-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)thiazol-2 -amine (100 mg, 0.164 mmol) in 1,4-dioxane (2 mL) was added 4 M HO in 1,4-dioxane (2 mL) at 0 °C and the reaction mixture was stirred at ambient temperature for 16 h. The mixture was concentrated under reduced pressure and the resulting residue was triturated with diethyl ether (30 mL), decanted and dried. The solid was then purified by prep-HPLC to yield 12 mg (15%) of the title compound. LCMS m / z = 479 [M+H]+; 'H-NMR (400 MHz, DMSO-d6): 5: 12.67 (bs, 1H), 8.84 (d, 1H), 7.63 (d, 1H), 7.44-7.39 (m, 2H), 7.06 (s, 1H), 6.08 (d, 1H), 3.04 (s, 3H), 2.37 (s, 3H). Example 299

[0762] N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3-cyclopropyl-5-fluo- ropyridin-2 -amine

[0763] Step 1: To a mixture of Intermediate 27 (0.3 g, 0.521 mmol) and 3-chloro-5-fluoropyridin-2-amine (0.153 g, 1.04 mmol) in THF (6.0 mL) at 0 °C was added boron trifluoride etherate (0.1 mL, 0.8 mmol) followed by trifluoroacetic acid (0.18 mL, 2.3 mmol). The resulting mixture was heated to 90 °C for 2 h in a sealed tube. The mixture was concentrated under reduced pressure to get the residue. The residue was diluted with ice water (50 mL) and adjusted the pH to 7.0 with sodium bicarbonate solution and extracted with ethyl acetate (2x100 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SC>4, filtered and concentrated under reduced pressure to get the crude product, which upon purification by GRACE flash chromatography [C18, 12 g, RP column] using acetonitrile and 0.1% FA in water as an eluent afforded 150 mg of 3-chloro-N-((3-chloro-4- fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)-5- fluoropyridin-2 -amine. LCMS m / z = 577 [M+H]+

[0764] Step 2: To a stirred solution of 3-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2-(trime- thylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)-5-fluoropyridin-2 -amine (0.05 g, 0.087 mmol) in a mixture of toluene: water (9:1) (2 mL) was added potassium phosphate (0.055 g, 0.260 mmol) ar ambient temperature. The miyture was degassed with argon for 5 minutes prior to the addition of cyclopropylboronic acid (0.007 g, 0.087 mmol), palladium(II) acetate (0.002 g, 0.009 mmol) and 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.007 g, 0.017 mmol). The reaction mixture was heated to 100 °C for 6 h. The mixture was fdtered through a celite pad, the resulting solution was diluted with water (20 mL) and extracted with ethyl acetate (2 x 30 mL). The combined organic layers were washed with brine (2 x 10 mL), dried over anhydrous Na2SC>4, filtered and concentrated under reduced pressure to get the crude compound, which upon purification by GRACE flash chromatography [Cl 8, 12 g, RP column] afforded 0.008 g (16%) of N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)-3-cyclopropyl-5-fluoropyridin-2 -amine. LCMS m / z = 583 [M+H]+

[0765] Step 3: To a solution of N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3- cyclopropyl-5-fluoropyridin-2 -amine (0.1 g, 0.17 mmol) in THF (2.0 mL) at 0 °C was added tetrabutylammonium fluoride (IM solution in THF, 0.662 mL, 0.662 mmol). The resulting reaction mixture was heated to 80 °C for 2 h. The mixture was concentrated under reduced pressure to get the crude residue. The residue was diluted with ice water (20 mL) and adjusted the pH to 7.0 with sodium bicarbonate solution and was extracted with 10% MeOH in DCM (2x25 mL). The combined extracts were washed with brine (2 x 10 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to get the cmde product, which upon purification by prep HPLC gave 25 mg of the title compound. LCMS m / z = 453 [M+H]+; 'H-NMR (400 MHz, DMSO-d6): 5: 7.81 (d, 1H), 7.66 (dd, 1H), 7.46-7.42 (m, 1H), 7.37 (t, 1H), 7.2 (dd, 1H), 6.82 (d, 1H), 6.40 (d, 1H), 3.06 (s, 3H), 2.38 (s, 3H),

[0766] 194-1.88 (m, 1H), 1.01-0.91 (m, 2H), 0.69-0.64 (m, 2H). Example 300-348

[0767] The title compounds were prepared using the following general synthetic method: to a solution of Intermediate 27 (50.0 mg, 86.78 pmol) and the appropriate reagents (5 equivaletns) in THF (1 mL) was added trifluoroborane ether complex (123.25 mg, 867.45 pmol). The resulting mixture was maintained at 80°C under stirring for 2h. The reaction progress was monitored by LCMS. After completion of the reaction the reaction mixture was evaporated under reduced pressure and purified by prep HPLC.

[0768] Example 349, 350

[0769] 2-(l-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)ethyl)-4-(methylsulfonyl)-lH-imidazole

[0770] Step 1: Mg (0.12 g, 5.07 mmol) was taken up in a two-neck flasked equipped with a reflux condenser and was dried under an argon atmosphere. Et2O (8.0 mL) was added, followed by the addition of a catalytic amount of I2. Then, a solution of l-(bromomethyl)-4-fluorobenzene (0.8 g, 4.23 mmol) in Et2O (3 mL) was added dropwise to the mixture at rt. The reaction mixture was stirred at rt for 1 h. To the freshly prepared Grignard reagent was then added a solution of intermediate 9a (0.3 g, 0.6 mmol) in Et2O (3 mL) at rt. The mixture was stirred at rt for 16 h. The reaction mixture was quenched with ammonium chloride solution. The aqueous layer was filtered through a celite bed and extracted with ethyl acetate (3 x 80 mL). The combined organic layers were washed with brine, dried over Na2SO4and concentrated under reduced pressure to get the crude product, which was purified by column chromatography to yield l-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)-l-(5-methanesulfonyl-l-{[2-(tri- methylsilyl) ethoxy] methyl}-lH-imidazol-2-yl) ethan-l-ol (0.33 g, 90%).

[0771] Step 2: To a solution of l-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl)-l-(5-methanesulfonyl-l-{[2-(trimethylsi- lyl) ethoxy] methyl}-lH-imidazol-2-yl) ethan-l-ol (0.2 g, 0.37 mmol) were added toluene (100.0 mL) and pTSA (0.06 g, 0.37 mmol) at rt. The reaction mixture was heated to 100 °C for 16 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. The residue was neutralized with sat. NaHCCL solution and extracted with ethyl acetate (3 x 60 mL). The combined organic layers were washed with brine, dried over Na2SO i and concentrated under reduced pressure to get the crude product, which was purified by column chromatography to obtain 2-[(E)-l-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl) ethenyl]-5-methanesulfonyl-lH-imidazole (0.13 g, 89%). LCMS m / z = 395 [M+H]+

[0772] Step 3: A solution of 2-[(E)-l-(3-chloro-4-fluorophenyl)-2-(4-fluorophenyl) ethenyl]-5-methanesulfonyl-lH-im- idazole (0.23 g, 0.57 mmol) in MeOH (20.0 mL) was degassed with N2for 15 minutes followed by the addition of PtO2(0.15 g) at rt. The reaction mixture was stirred at 80 °C in an autoclave vessel under 10.3 bar H2gas pressure for 16 h. The reaction mixture was cooled to rt and filtered through celite. The filtrate was concentrated under reduced pressure to get the crude product, which was purified by reverse phase prep. HPLC and chiral HPLC to get the title compound as individual enantiomers.

[0773] Peak 1, example 349: Yield: 31% (0.115 g, 0.289 mmol). LCMS m / z = 397 [M+H]+; 'H-NMR (400 MHz, DMSO- de): 12.72 (s, 1H), 7.74 (s, 1H), 7.54 (d, 1H), 7.37-7.30 (m, 2H), 7.18-7.14 (m, 2H), 7.04-6.99 (m, 2H), 4.44-4.40 (m, 1 H), 3.48-3.42 (m, 1H), 3.24-3.18 (m, 1H), 3.09 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 pm; mobile phase: hexane / DCM / EtOH / iPrNH260 / 20 / 20 / 0.1; flow rate: 1.0 mL / min; Rt = 4.83 min (first eluting).

[0774] Peak 2, example 350: Yield: 30% (0.11 g, 0.277 mmol). LCMS m / z = 397 [M+H]+; 'H-NMR (400 MHz, DMSO- d6): 12.72 (s, 1H), 7.74 (s, 1H), 7.54 (d, 1H), 7.37-7.30 (m, 2H), 7.18-7.14 (m, 2H), 7.04-6.99 (m, 2H), 4.44-4.40 (m, 1H), 3.48-3.42 (m, 1H), 3.24-3.18 (m, 1H), 3.09 (s, 3H). Chiral HPLC: column: Chiralpak IC (4.6 x 250 mm) 5 pm; mobile phase: hexane / DCM / EtOH / iPrNH260 / 20 / 20 / 0.1; flow rate: 1.0 mL / min; Rt = 5.38 min (second eluting).

[0775] Example 351, 352

[0776] (2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfa- none

[0777] Step-1: To a stirred solution of Intermediate 34a (1.8 g, 3.52 mmol, 1.0 equiv.) in MeOH (80 mL) were added diacetoxyiodobenzene (211.3 g, 35.22 mmol, 10.0 equiv.) and ammonium carbonate (3.4 g, 35.22 mmol, 10.0 equiv.) at room temperature. Reaction mixture was stirred at room temperature for 2 h. Reaction mixture was washed with water and extracted with ethyl acetate (3 x 200 mL). Combined organic part was washed with cold brine and dried over Na2SC>4. Organic layer was concentrated under reduced pressure to get cmde. Resulting crude was purified by combi flash column chromatography (Silica gel, 0-100% ethyl acetate in hexane as eluent.) to get (2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-4-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imid- azol-5-yl)(imino)(methyl)-16-sulfanone. Yield: 63% (1.2 g, 2.2 mmol). LCMS: m / z [M+H]+= 542.2,

[0778] Step-2: To a stirred solution of the product of Step-1 (0.2 g, 0.37 mmol, 1.0 equiv.) in AcOH (10 mL) and H2O (2 mL) was heated at 70 °C for 2 h. Reaction mixture was cooled to room temperature and evaporated under reduced pressure to get crude. Crude was basified with saturated NaHC'CL. Aqueous part was extracted with ethyl acetate (3 x 80 mL) and washed with brine. Combined organic layer was dried over Na2SO i. filtered and evaporated under reduced pressure to get the cmde product. The crude was purified through combi flash column chromatography (0-20% MeOH in EtOAc as eluent) to obtain racemic title compound, followed by normal phase chiral separation.

[0779] LCMS: 412.2 m / z [M+H]+. ' H NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm): 12.75 (s, 1H), 7.79-7.77 (m, 1H), 7.56-7.52 (m, 1H), 7.47-7.43 (m, 1H), 7.14-7.05 (m, 4H), 6.54 (s, 1H), 3.92 (s, 1 H), 2.96 (s, 3H), 2.39 (s, 3H). Analytical chiral HPLC: Chiralpak IC (4.6 x 250 mm) 5 pm, mobile phase: 0.5% isopropylamine in iPrOH; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 97 bar ; T: 35 °C; 351 (Yield: 20 mg) first eluting enantiomer, Rt = 2.49 min. 352 (Yield: 23 mg): second eluting enantiomer, Rt = 3.22 min. Example 353, 354

[0780] (2-((4-chloro-3-fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(me- thyl)-16-sulfanone

[0781] The title compounds were prepared from Intermediate 34b using an analogous method to that described for Example 351 / 352. LCMS: 412.2 m / z [M+H]+.!H NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm): 12.75 (s, 1H), 7.79- 7.77 (m, 1H), 7.55-7.52 (m, 1H), 7.48-7.43 (m, 1H), 7.14-7.05 (m, 4H), 6.54 (s, 1H), 3.93 (s, 1 H), 2.96 (s, 3H), 2.39 (s, 3H). Analytical chiral HPLC: Chiralpak IC (4.6 x 250 mm) 5 pm, mobile phase: 0.5% siopropylamine in iPrOH; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 97 bar ; T: 35 °C; 353 (Yield: 35 mg) first eluting enantiomer, Rt = 1.87 min. 354 (Yield: 40 mg): second eluting enantiomer, Rt = 2.71 min.

[0782] Example 355-358

[0783] (2-((3-chloro-4-fluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0784] To a solution Intermediate 20 (500 mg, 0.86 mmol, 1.0 equiv.) in DCM (20 mL) were added trans-4-(trifluorome- thyl)cyclohexan-l-ol (365 mg, 2.17 mmol, 2.5 equiv.), BF3-OEt2 (0.2 mL, 1.3 mmol, 1.5 equiv.) and TFA (0.4 mL, 4.36 mL, 5.0 equiv.) and stirred at RT for 2 h. To the reaction mixture was added TFA (2 mL) (for complete SEM deprotection) and stirred at RT for 16 h. The reaction mixture was concentrated under reduced pressure to get a residue which was diluted with ethyl acetate (100 mL). The organic part was washed with NaHCO3solution (50 mL), brine (50 mL) and dried over anhydrous sodium sulfate. Solvent was concentrated under reduced pressure to afford cmde product which was purified by RP prep HPLC to get the stereoisomeric mixture of the 4 title compounds. Stereosiomers were separated by chiral SFC.

[0785] Preparative first chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: isopropanol, flow: 70 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 355 and 356, second eluting: 357, third eluting: 358.

[0786] Preparative second chiral SFC: column: I Cellulose Z (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 100 mL / min; % of co-solvent: 20%; ABPR: 100 bar; T: 35 °C. First eluting: 355, second eluting: 356. 355: Yield: 8% (33 mg, 0.07 mmol). LC-MS: m / z [M+H]+= 468.3.1H-NMR (400 MHz, DMS0-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.65-7.63 (m, 1H), 7.44-7.39 (m, 2H), 5.69 (s, 1 H), 3.88 (bs, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.24-2.20 (m, 1H), 2.07-2.06 (m, 2H), 1.90-1.83 (m, 2H), 1.34-1.17 (m, 4H). 356: Yield: 8% (33 mg, 0.07 mmol). LC-MS: m / z [M+H]+= 468.3. 'H-NMR (400 MHz, DMS0-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.64-7.62 (m, 1H), 7.44-7.39 (m, 2H), 5.69 (s, 1 H), 3.84 (bs, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.24-2.20 (m, 1H), 2.07-2.03 (m, 2H), 1.87-1.84 (m, 2H), 1.35-1.17 (m, 4H). 357: Yield: 8% (33 mg, 0.07 mmol). LC-MS: m / z [M+H]+= 468.3. 'H-NMR (400 MHz, DMS0-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.64-7.62 (m, 1H), 7.44-7.39 (m, 2H), 5.69 (s, 1 H), 3.93 (bs, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.24-2.20 (m, 1H), 2.07-2.03 (m, 2H), 1.90-1.84 (m, 2H), 1.35- 1.15 (m, 4H). 358: Yield: 8% (33 mg, 0.07 mmol). LC-MS: m / z [M+H]+= 468.3. 'H-NMR (400 MHz, DMS0-d6, 25 °C) 5 (ppm)= 12.44 (s, 1H), 7.65-7.63 (m, 1H), 7.44-7.39 (m, 2H), 5.69 (s, 1 H), 3.93 (bs, 1H), 2.96 (s, 3H), 2.37 (s, 3H), 2.24-2.20 (m, 1H), 2.06-2.03 (m, 2H), 1.90-1.83 (m, 2H), 1.35-1.15 (m, 4H).

[0787] Example 359-362

[0788] (2-((3-chloro-4-fluorophenyl)((3,3-difluorocyclobutyl)methoxy)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(me- thyl)-16-sulfanone

[0789] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example Example 355-358. Stereosiomers were separated by chiral SFC.

[0790] Preparative first chiral SFC: column: Chiralpak IG (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 359 and 360, second eluting: mixture of 361 and 362.

[0791] Preparative second chiral SFC: column:! Cellulose Z (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 100 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: 359, second eluting: 360.

[0792] Preparative third chiral SFC: column:! Cellulose Z (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 100 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: 361, second eluting: 362.

[0793] 359: Yield: 19 mg. LC-MS: m / z [M+H]+= 422.1. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.48 (br, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.45-7.38 (m, 2H), 5.54 (s, 1H), 3.85 (br, 1H), 3.46-3.45 (m, 2H), 2.96 (s, 3H), 2.66-2.59 (m, 2H), 2.43-2.32 (m, 6H). 360: Yield: 12 mg. LC-MS: m / z [M+H]+= 422.1. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.47 (br, 1H), 7.64 (d, J = 7.12 Hz, 1H), 7.45-7.39 (m, 2H), 5.54 (s, 1H), 3.85 (br, 1H), 3.47-3.45 (m, 2H), 2.95 (s, 3H), 2.66-2.59 (m, 2H), 2.45-2.32 (m, 6H). 361: Yield: 13 mg. LC-MS: m / z [M+H]+= 422.1. 'H- NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.48 (br, 1H), 7.65-7.63 (m, 1H), 7.45-7.37 (m, 2H), 5.54 (s, 1H), 3.85 (br, 1H), 3.46 (d, J=8 Hz, 2H), 2.95 (s, 3H), 2.66-2.59 (m, 2H), 2.43-2.32 (m, 6H). 362: Yield: 20 mg. LC- MS: m / z [M+H]+= 422.1. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.48 (br, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.45-7.40 (m, 2H), 5.54 (s, 1H), 3.85 (br, 1H), 3.46-3.45 (m, 2H), 2.96 (s, 3H), 2.66-2.59 (m, 2H), 2.43-2.32 (m, 6H).

[0794] Example 363-366

[0795] (2-((3-chloro-4-fluorophenyl)((4-fluorobenzyl)oxy)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sul- fanone

[0796] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method but heating at 80°C for 16h in asealed vial, to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0797] Preparative first chiral SFC: column: I Cellulose Z (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 100 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 363, second eluting: mixture of 364 and 365, third eluting: 366.

[0798] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: isopropanol, flow: 100 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C. First eluting: 364, second eluting: 365.

[0799] 363: Yield: 23 mg. LC-MS: m / z [M+H]+= 426.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.56 (s, 1H), 7.67 (d, J = 7.44 Hz, 1H), 7.44-7.38 (m, 4H), 7.18 (t, J = 8.72 Hz, 2H) 5.60 (s, 1 H), 4.47 (s, 2H), 3.86 (s, 1H), 2.96 (s, 3H), 2.37(s, 3H). 364: Yield: 23 mg. LC-MS: m / z [M+H]+= 426.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.56 (s, 1H), 7.67 (d, J = 7.2 Hz, 1H), 7.44-7.38 (m, 4H), 7.18 (t, J = 8.72 Hz, 2H) 5.60 (s, 1 H), 4.48 (s, 2H), 3.86 (s, 1H), 2.95 (s, 3H), 2.37(s, 3H). 365: Yield: 23 mg. LC-MS: m / z [M+H]+= 426.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.56 (s, 1H), 7.67 (d, J = 6.64 Hz, 1H), 7.44-7.38 (m, 4H), 7.18 (t, J = 8.84 Hz, 2H) 5.60 (s, 1 H), 4.48 (s, 2H), 3.86 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H). 366: Yield: 23 mg. LC-MS: m / z [M+H]+= 426.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.56 (s, 1H), 7.67 (d, J = 7.2 Hz, 1H), 7.44- 7.38 (m, 4H), 7.18 (t, J = 8.76 Hz, 2H) 5.60 (s, 1 H), 4.47 (s, 2H), 3.86 (s, 1H), 2.96 (s, 3H), 2.37(s, 3H).

[0800] Example 367-370

[0801] (2-((3-chloro-4-fluorophenyl)((4,4-difluorocyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(me- thyl)-16-sulfanone The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0802] Preparative first chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 90 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 367 and 368, second eluting: 369, third eluting: 370.

[0803] Preparative second chiral SFC: column: I Cellulose Z (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 70 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: 367, second eluting: 368.

[0804] 367: Yield: 6%. LC-MS: m / z [M+H]+= 436.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.43 (bs, 1H), 7.65-7.64 (m, 1H) 7.43-7.41 (m, 2H), 5.68 (s, 1H), 3.85 (s, 1H), 3.58 (bs, 1H), 2.95 (s, 3H), 2.39 (s, 3H), 2.03- 1.99 (m, 2H), 1.89-1.80 (m, 2H), 1.81-1.75 (m, 4H). 368: Yield: 3%. LC-MS: m / z [M+H]+= 436.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.43 (bs, 1H), 7.65-7.64 (m, 1H) 7.43-7.41 (m, 2H), 5.68 (s, 1H), 3.85 (s, 1H), 3.58 (bs, 1H), 2.95 (s, 3H), 2.39 (s, 3H), 2.01-1.96 (m, 2H), 1.89-1.82 (m, 2H), 1.81-1.75 (m, 4H). 369: Yield: 3%. LC-MS: m / z [M+H]+= 436.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.44 (bs, 1H), 7.65-7.63 (m, 1H) 7.43-7.41 (m, 2H), 5.68 (s, 1H), 3.86 (s, 1H), 3.58 (bs, 1H), 2.94 (s, 3H), 2.38 (s, 3H), 2.02-1.95 (m, 2H), 1.88- 1.80 (m, 2H), 1.80-1.74 (m, 4H). 370: Yield: 7%. LC-MS: m / z [M+H]+= 436.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.44 (bs, 1H), 7.65-7.64 (m, 1H) 7.43-7.41 (m, 2H), 5.68 (s, 1H), 3.86 (s, 1H), 3.57 (bs, 1H), 2.95 (s, 3H), 2.38 (s, 3H), 2.0-1.95 (m, 2H), 1.88-1.80 (m, 2H), 1.79-1.71 (m, 4H).

[0805] Example 371-374

[0806] (2-((3-chlorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0807] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0808] Preparative first chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: isopropanol, flow: 100 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 371 and 372, second eluting: 373, third eluting: 374.

[0809] Preparative second chiral SFC: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 70 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: 371, second eluting: 372.

[0810] 371: Analytical Chiral HPLC condition: Chiral SFC: column: I-CELLULOSE C (4.6 x 150 mm), 5.0 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 1450 psi; T: 35 °C; Rt = 1.97 min. LC-MS: m / z [M+H]+= 450.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.41 (s, 1H), 7.50 (s, 1H), 7.39-7.33 (m, 3H), 5.67 (s, 1H), 3.83 (s, 1H), 3.31 (s, 1H, masked with water peak), 2.95 (s, 3H), 2.36 ( s, 3H), 2.32-2.21 (m, 1H), 2.08-2.05 (m, 2H), 1.86-1.83 (m, 2H), 1.31-1.20 (m, 4H). 372: Analytical Chiral HPLC condition: Chiral SFC: column: I-CELLULOSE C (4.6 x 150 mm), 5.0 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 1450 psi; T: 35 °C; Rt = 2.42 min. LC-MS: m / z [M+H]+= 450.3.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.49 (s, 1H), 7.38-7.35 (m, 3H), 5.68 (s, 1H), 3.85 (s, 1H), 3.31 (s, 1H, masked with water peak), 2.95 (s, 3H), 2.37 ( s, 3H), 2.32-2.21 (m, 1H), 2.08-2.06 (m, 2H), 1.87-1.84 (m, 2H), 1.32-1.20 (m, 4H). 373: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK -01 (4.6 x 150 mm), 3.5 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 35%; ABPR: 1595 psi; T: 35 °C; Rt = 3.67 min. LC-MS: m / z [M+H]+= 450.3.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.42 (s, 1H), 7.49 (s, 1H), 7.39-7.33 (m, 3H), 5.68 (s, 1H), 3.83 (s, 1H), 3.31 (s, 1H), 2.95 (s, 3H), 2.37 ( s, 3H), 2.32-2.21 (m, 1H), 2.08-2.06 (m, 2H), 1.87-1.84 (m, 2H), 1.32-1.20 (m, 4H). 374: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK-01 (4.6 x 150 mm), 3.5 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 35%; ABPR: 1595 psi; T: 35 °C; Rt = 4.51 min. LC-MS: m / z [M+H]+= 450.3.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppml2.42 (s, 1H), 7.50 (s, 1H), 7.41-7.33 (m, 3H), 5.67 (s, 1H), 3.86 (s, 1H), 3.30 (s, 1H), 2.96 (s, 3H), 2.37 ( s, 3H), 2.25-2.23 (m, 1H), 2.08-2.05 (m, 2H), 1.87-1.84 (m, 2H), 1.35-1.18 (m, 4H).

[0811] Example 375-378 imino(methyl)(5-methyl-2-((((trans)-4-(trifluoromethyl)cyclohexyl)oxy)(3-(trifluoromethyl)phenyl)methyl)-lH- imidazol-4-yl)-16-sulfanone

[0812] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0813] Preparative first chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 20%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 375 and 376, second eluting: 377, third eluting: 378.

[0814] Preparative second chiral SFC: column: I Cellulose C (21.1 mm><250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 60 mL / min; % of co-solvent: 20%; ABPR: 100 bar; T: 35 °C. First eluting: 375, second eluting: 376.

[0815] 375: Analytical Chiral HPLC condition: Chiral SFC: column: CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt = 2.37 min. LC-MS: m / z [M+H]+= 484.3.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.48 (s, 1H), 7.81 (s, 1H), 7.69-7.66 (m, 2H), 7.62-7.60 (m, 1H), 5.79 (s, 1H), 3.85 (s, 1H), 3.35-3.33 (m, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.26-2.21 (m, 1H), 2.08 (d, J= 9.76 Hz, 2H), 1.85 (d, J= 12.12 Hz, 2H), 1.34-1.21 (m, 4H). 376: Analytical Chiral HPLC condition: Chiral SFC: column CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt = 2.87 min. LC-MS: m / z [M+H]+= 484.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.48 (s, 1H), 7.80 (s, 1H), 7.66- 7.62 (m, 2H), 7.62-7.60 (m, 1H), 5.79 (s, 1H), 3.85 (s, 1H), 3.35-3.33 (m, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.26- 2.21 ( m, 1H), 2.08 (brs, 2H), 1.85 (d, J= 12.12 Hz, 2H), 1.34-1.21 (m, 4H). 377: Analytical Chiral HPLC condition: Chiral SFC: column: ((R, R) WHELK -01 (4.6 x 150 mm), 3.5 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1000 psi; T: 35 °C; Rt =2.72 min. LC-MS: m / z [M+H]+= 484.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.50 (s, 1H), 7.80 (s, 1H), 7.66-7.62 (m, 2H), 7.62-7.60 (m, 1H), 5.79 (s, 1H), 3.35-3.33 (m, 1H), 2.97 (s, 3H), 2.37 (s, 3H), 2.26-2.21 (m, 1H), 2.07 (brs, 2H), 1.85 (d, J= 12.12 Hz, 2H), 1.31-1.21 (m, 4H). 378: Analytical Chiral HPLC condition: Chiral SFC: column(R, R) WHELK-01 (4.6 x 150 mm), 3.5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1000 psi; T: 35 °C; Rt =3.40 min. LC-MS: m / z [M+H]+= 484.3.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 12.50 (s, 1H), 7.81 (s, 1H), 7.69-7.66 (m, 2H), 7.62-7.60 (m, 1H), 5.79 (s, 1H), 3.85 (s, 1H), 3.35-3.33 (m, 1H), 2.98 ( s, 3H), 2.37 (s, 3H), 2.26-2.21 ( m, 1H), 2.08 (d, J= 9.76 Hz, 2H), 1.85 (d, J= 12.12 Hz, 2H), 1.34-1.21 (m, 4H).

[0816] Example 379-382 imino(methyl)(5-methyl-2-((((trans)-4-(trifluoromethyl)cyclohexyl)oxy)(4-(trifluoromethyl)phenyl)methyl)-lH- imidazol-4-yl)-16-sulfanone

[0817] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0818] Preparative chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent 0.2% (7N Ammonia in MeOH) in isopropanol, flow: 100 mL / min; % of co-solvent: 20%; ABPR: 100 bar; T: 35 °C. Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK-01 (4.6 x 150 mm), 3.5 pm, mobile phase 0.3 % iPrNH2in isopropanol; flow: 3 mL / min; % of co-solvent: 20%; ABPR: 1000 psi; T: 35 °C. First eluting: 379 second eluting: 380, third eluting: 381, forth eluting: 382.

[0819] 379: 6%, Rt = 3.68 min (first eluting). LC-MS: m / z [M+H]+= 484.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.75-7.73 (m, 2H), 7.64-7.62 (m, 2H), 5.77 (s, 1H), 3.83 (s, 1H), 3.36-3.35 (m, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.23 ( brs, 1H), 2.10-2.07 (m, 2H), 1.85 (d, J= 11.64 Hz, 2H), 1.33-1.21 (m, 4H). 380: 6%, Rt = 3.82 min (second eluting). LC-MS: m / z [M+H]+= 484.3.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.75-7.73 (m, 2H), 7.64-7.62 (m, 2H), 5.77 (s, 1H), 3.83 (s, 1H), 3.36-3.35 (m, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.23( brs, 1H), 2.10-2.07 (d, J= 11.48 Hz, 2H), 1.85 (d, J= 11.64 Hz, 2H), 1.33-1.21 (m, 4H). 381: 3%, Rt = 5.28 min (third eluting). LC-MS: m / z [M+H]+= 484.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.75-7.73 (m, 2H), 7.64-7.62 (m, 2H), 5.77 (s, 1H), 3.83 (s, 1H), 3.36-3.35 (m, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.23( brs, 1H), 2.10-2.07 (d, J= 11.48 Hz, 2H), 1.85 (d, J= 11.64 Hz, 2H), 1.33-1.21 (m, 4H). 382: 3%, Rt = 6.20 min (forth eluting). LC-MS: m / z [M+H]+= 484.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.43 (s, 1H), 7.75-7.73 (m, 2H), 7.64-7.62 (m, 2H), 5.77 (s, 1H), 3.83 (s, 1H), 3.36-3.35 (m, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.24-2.23 ( m, 1H), 2.10-2.07 (d, J= 11.48 Hz, 2H), 1.85 (d, J= 11.64 Hz, 2H), 1.33-1.21 (m, 4H).

[0820] Example 383-386

[0821] (2-((3-(difluoromethyl)phenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0822] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0823] Preparative first chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent 0.2% (7N ammonia in methanol) in isopropanol, flow: 70 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T : 35 °C. First eluting: mixture of 383 and 384, second eluting: 385, third eluting: 386.

[0824] Preparative second chiral SFC: column CHIRALPAK IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 70 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 383, second eluting: 384.

[0825] 383: Analytical Chiral HPLC condition: Chiral SFC: column: CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt = 1.67 min. LC-MS: m / z [M+H]+= 465.9. 384: Analytical Chiral HPLC condition: Chiral SFC: column: CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt = 2.03 min. LC-MS: m / z [M+H]+= 465.9. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.45 (s, 1H), 7.63 (s,lH), 7.56-7.53 (m, 1H), 7.51-7.48 (m, 2H), 7.05 (t, J= 55.7 Hz, 1H), 5.73 (s, 1H), 3.85 (s, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.25-2.21 (m,lH), 2.08 (d, J= 11.6 Hz, 2H), 1.85 (d, J= 13.0 Hz, 2H), 1.33-1.20 (m, 4H). 385: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK- 01 (4.6 mm x 150 mm), 3.5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of cosolvent: 40%; ABPR: 1595 psi; T: 35 °C; Rt = 1.67 min. LC-MS: m / z [M+H]+= 465.9. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.43 (s, 1H), 7.63 (s, 1H), 7.54-7.49 (m, 3H) , 7.04 (t, J= 55.7 Hz, 1H), 5.73 (s, 1H), 3.83 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.25-2.21 (m, 1H), 2.08 (d, J= 11.6 Hz, 2H), 1.85 (d, J= 13.0 Hz, 2H), 1.36-1.17 (m, 4H). 386: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK-01 (4.6 mm x 150 mm), 3.5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 40%; ABPR: 1595 psi; T: 35 °C; Rt = 2.08 min. LC-MS: m / z [M+H]+= 465.9. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)12.45 (s, 1H), 7.64 (s, 1H), 7.55-7.50 (m, 3H) , 7.04 (t, J= 55.7 Hz, 1H), 5.73 (s, 1H), 3.85 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.25-2.23 (m, 1H), 2.08 (d, J= 11.6 Hz, 2H), 1.85 (d, J= 12.4 Hz, 2H), 1.36-1.17 (m, 4H). Example 387-390

[0826] (2-((3,5-difluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0827] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0828] Preparative first chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent 0.2% (7N ammonia in methanol) in isopropanol, flow: 120 mL / min; % of co-solvent: 20%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 387 and 388, second eluting: 389, third eluting: 390.

[0829] Preparative second chiral SFC: column I Cellulose C (21.1 mm><250 mm ), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 70 mL / min; % of co-solvent: 25%; ABPR: 100 bar; T: 35 °C. First eluting: 387, second eluting: 388.

[0830] 387: Analytical Chiral HPLC condition: Chiral SFC: column: CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt = 2.56 min. LC-MS: m / z [M+H]+= 452.3.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.44 (s, 1H), 7.20- 7.13 (m, 3H), 5.71 (s, 1H), 3.87 (s, 1H), 3.36-3.35 (m, 1H), 2.96 ( s, 3H), 2.37 (s, 3H), 2.25-2.23 ( m, 1H), 2.10- 2.07 (m, 2H), 1.85 (d, J= 13.12 Hz, 2H), 1.32-1.21 (m, 4H). 388: Analytical Chiral HPLC condition: Chiral SFC: column: CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt = 2.95 min. LC-MS: m / z [M+H]+= 452.3.1H- NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.44 (s, 1H), 7.20-7.13 (m, 3H), 5.71 (s, 1H), 4.19 (brs, 1H), 3.36- 3.35 (m, 1H), 2.98 ( s, 3H), 2.38 (s, 3H), 2.25-2.23 ( m, 1H), 2.10-2.05 (m, 2H), 1.85 (d, J= 13.12 Hz, 2H), 1.32- 1.17 (m, 4H). 389: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK -01 (4.6 mm x 150 mm), 3.5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 20%; ABPR: 1595 psi; T: 35 °C; Rt = 6.55 min. LC-MS: m / z [M+H]+= 452.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.43 (s, 1H), 7.20-7.12 (m, 3H), 5.71 (s, 1H), 3.86 (s, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.25-2.23 ( m, 1H), 2.10- 2.05 (m, 2H), 1.85 (d, J= 13.12 Hz, 2H), 1.35-1.18 (m, 4H). 390: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK-01 (4.6 mm x 150 mm), 3.5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 20%; ABPR: 1595 psi; T: 35 °C; Rt = 7.10 min. LC-MS: m / z [M+H]+= 452.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.43 (s, 1H), 7.20-7.13 (m, 3H), 5.71 (s, 1H), 3.85 (s, 1H), 3.36- 3.35 (m, 1H), 2.96 ( s, 3H), 2.37 (s, 3H), 2.25-2.23 ( m, 1H), 2.10-2.07 (m, 2H), 1.85 (d, J= 13.12 Hz, 2H), 1.32- 1.21 (m, 4H). Example 391-394

[0831] (2-((4-(difluoromethyl)phenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0832] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0833] Preparative first chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 70 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 391 and 392, second eluting: 393, third eluting: 394.

[0834] Preparative second chiral SFC: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 60 mL / min; % of co-solvent: 25%; ABPR: 120 bar; T: 35 °C. First eluting: 391, second eluting: 392.

[0835] 391: Analytical Chiral HPLC condition: Chiral SFC: column: CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 1000 psi; T: 35 °C; Rt = 1.62 min. LC-MS: m / z [M-H]’ = 464.1 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.42 (s, 1H), 7.56- 7.53 (m, 4H), 7.15-6.87 (m, 1H), 5.72 (s, 1H), 3.84 (s, 1H), 2.95 (s, 3H), 2.37 ( s, 3H), 2.28-2.21 (m, 1H), 2.10- 2.07 (m, 2H), 1.87-1.84 (m, 2H), 1.33-1.20 (m, 4H). 392: Analytical Chiral HPLC condition: Chiral SFC: column: CHIRALPAK IC (4.6 x 250 mm), 5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 1000 psi; T: 35 °C; Rt= 2.93 min. LC-MS: m / z [M+H]+= 466.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.49 (s, 1H), 7.56 (s, 4H), 7.15-6.87 (m, 1H), 5.72 (s, 1H), 4.70 (s, 1H), 3.01 (s, 3H), 2.37 ( s, 3H), 2.32-2.23 (m, 1H), 2.10-2.07 (m, 2H), 1.87-1.84 (m, 2H), 1.33-1.17 (m, 4H). 393: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK-01 (4.6 mm x 150 mm), 3.5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 1450 psi; T: 35 °C; Rt = 1.67 min. LC-MS: m / z [M+H]+= 466.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.42 (s, 1H), 7.57-7.55 (m, 4H), 7.15-6.87 (m, 1H), 5.71 (s, 1H), 3.83 (s, 1H), 2.95 (s, 3H), 2.36 ( s, 3H), 2.36-2.32 (m, 1H), 2.09-2.07 (m, 2H), 1.86-1.84 (m, 2H), 1.32-1.20 (m, 4H). 394: Analytical Chiral HPLC condition: Chiral SFC: column: (R, R) WHELK-01 (4.6 mm x 150 mm), 3.5 pm, mobile phase 0 .5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; ABPR: 1450 psi; T: 35 °C; Rt = 2.08 min. LC-MS: m / z [M+H]+= 466.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.41 (s, 1H), 7.55 (s, 4H), 7.15-6.87 (m, 1H), 5.71 (s, 1H), 3.83 (s, 1H), 2.95 (s, 3H), 2.37 ( s, 3H), 2.36-2.32 (m, 1H), 2.09-2.07 (m, 2H), 1.86-1.84 (m, 2H), 1.32-1.20 (m, 4H). Example 395-398

[0836] (2-((3 -chloro-4-fluorophenyl)((3 -(trifluoromethyl)bicyclo [1.1. l]pentan- 1 -yl)methoxy)methyl)-5-methyl- IH-imi- dazol-4-yl)(imino)(methyl)-16-sulfanone

[0837] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 355-358. Stereosiomers were separated by chiral SFC.

[0838] Preparative first chiral SFC: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 110 mL / min; % of co-solvent: 35%; ABPR: 120 bar; T: 35 °C. First eluting: mixture of 395 and 396, second eluting: mixture of 397 and 398.

[0839] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 70 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: 395, second eluting: 396.

[0840] Preparative third chiral SFC: column: (R,R) -Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in methanol, flow: 100 mL / min; % of co-solvent: 25%; ABPR: 100 bar; T: 35 °C. First eluting: 397, second eluting: 398.

[0841] 395: LC-MS: m / z [M-H+= 466.2 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.44 (bs, 1H), 7.63 (d, J = 3.77 Hz, 1H), 7.41 (t, J = 8.88 Hz, 2H), 5.52 (s, 1H), 3.86 (s, 1H), 3.49-3.48 (m, 2H), 2.95 (s, 3H), 2.38 (s, 3H), 1.92 (s, 6H). 396: LC-MS: m / z [M-H]+= 466.2 ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.44 (bs, 1H), 7.64-7.62 (m, 1H), 7.43-7.39 (m, 2H), 5.52 (s, 1H), 3.86 (s, 1H), 3.52-3.45 (m, 2H), 2.95 (s, 3H), 2.38 (s, 3H), 1.92 (s, 6H). 397: LC-MS: m / z [M-H]+= 466.2 ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.44 (bs, 1H), 7.64 (d, J = 6.84 Hz, 1H), 7.46-7.42 (m, 2H), 5.52 (s, 1H), 3.86 (s, 1H), 3.49-3.47 (m, 2H), 2.95 (s, 3H), 2.38 (s, 3H), 1.93 (s, 6H). 398: LC-MS: m / z [M-H]+= 466.2 ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm) 12.44 (bs, 1H), 7.63 (d, J = 7.16 Hz, 1H), 7.44-7.40 (m, 2H), 5.52 (s, 1H), 3.88 (s, 1H), 3.52-3.45 (m, 2H), 2.96 (s, 3H), 2.38 (s, 3H), 1.92 (s, 6H).

[0842] Example 399-402

[0843] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 395. Example 403-406

[0844] (2-((4-chloro-3-fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(me- thyl)-16-sulfanone

[0845] Step 1: To a stirred soltion of (4-chloro-3-fluorophenyl)(4-iodo-5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2-yl)methyl diisopropylcarbamate Intermediate 22 (1.5g, 2.404 mmol) and 5-chloropyridin-2-amine (0.464 g, 3.606 mmol) in THF (30 mL) were added boron trifluoride etherate (0.45mL, 1.5 mmol) and trifluoroacetic acid (0.8 mL, 10 mmol) at ambient temperature. The resulting reaction mixture was heated to 80 °C for 1 h. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with aq. NaHC'CL solution (2x 100 mL). The combined organic layers were dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography (SiCK 15% EtOAc / PE) to afford 5-chloro-N-((4-chloro-3- fluorophenyl)(4-iodo-5-methyl-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)pyridin-2 -amine (1.0 g, 68%).

[0846] Step 2: To a continuously argon-purged solution of 5-chloro-N-((4-chloro-3-fluorophenyl)(5-iodo-4-methyl-l-((2- (trimethylsilyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)pyridin-2-amine (1.5 g, 2.470 mmol) in 1,4-dioxane (30 mL) were added cesium carbonate (2.4 g, 7.4 mmol), sodium thiomethoxide (0.260 g, 3.705 mmol), Xantphos (0.214 g, 0.370 mmol) and Pd2(dba)s (0.226 g, 0.247 mmol) at ambient temperature. The resulting reaction mixture was stirred for 18 h at 120 °C. The reaction mixture was fdtered through a pad of celite and concentrated under reduced pressure. The resulting crude product was purified by flash column chromatography to afford 5-chloro- N-((4-chloro-3 -fluorophenyl)(4-methyl-5-(methylthio)- 1 -((2-(trimethylsilyl)ethoxy)methyl)- lH-imidazol-2- yl)methyl)pyridin-2-amine (0.65 g, 50%).

[0847] Step 3.- To a stirred solution of 5-chloro-N-((4-chloro-3-fluorophenyl)(4-methyl-5-(methylthio)-l-((2-(trimethylsi- lyl)ethoxy)methyl)-lH-imidazol-2-yl)methyl)pyridin-2-amine (0.6 g, 1.137 mmol) in MeOH (15 mL) at ambient temperature were added (diacetoxyiodo)benzene (1.1 g, 3.4 mmol) and ammonium carbonate (0.536 g, 3.4 mmol). The reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was concentrated under reduced pressure to get (2-((4-chloro-3-fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-4-methyl-l-((2-(tri- methylsilyl)ethoxy)methyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone (0.8 g, crude).

[0848] Step 4 : (2-((4-chloro-3 -fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-4-methyl- 1 -((2-(trimethylsilyl)eth- oxy)methyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone (0.8 g, 1.432 mmol) was dissolved in hydrochloric acid (4N solution in 1,4-dioxane, 10 mL) at ambient temperature and the mixture was stirred for 18 h. The reaction mixture was concentrated under reduced pressure to obtain the crude product, which was purified by prep HPLC and then chiral SFC to get the title compound. Analytical chiral SFC: column: Chiralpak AD-H (4.6 x 250 mm) 5 pm; co-solvent: 0.5% (7N NH3 in methanol) in iPrOH, flow: 3 mL / min; % of co-solvent: 25%; ABPR: 1500 psi T: 30 °C; 403: Rt = 3.47 min (first eluting); 404: Rt = 3.66 min (second eluting); 405: Rt = 5.07 min (third eluting); 406: Rt = 7.80 min (fourth eluting).

[0849] 403: Yield: 29 mg, 5%; LCMS m / z = 427 [M+H]+; ’H-NMR (400 MHz, DMSO-de): 12.50 (s, 1H), 7.95 (d, 1H), 7.78 (d, 1H), 7.57-7.48 (m, 2H), 7.43 (dd, 1H), 7.26 (dd, 1H), 6.77 (d, 1H), 6.27 (d, 1H), 3.82 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H). 404: Yield: 26 mg; LCMS m / z = 427 [M+H]+; ’H-NMR (400 MHz, DMSO-de): 12.51 (s, 1H), 7.95 (d, 1H), 7.78 (d, 1H), 7.57-7.48 (m, 2H), 7.43 (dd, 1H), 7.26 (dd, 1H),), 6.77 (d, 1H), 6.27 (d, 1H), 3.83 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H). 405: Yield: 31 mg; LCMS m / z = 427 [M+H]+; ’H-NMR (400 MHz, DMSO-de): 12.51 (s, 1H), 7.95 (d, 1H), 7.78 (d, 1H), 7.57-7.48 (m, 2H), 7.43 (dd, 1H), 7.26 (dd, 1H), 6.77 (d, 1H), 6.27 (d, 1H), 3.82 (s, 1H), 2.95 (s, 3H), 2.36 (s, 3H). 406: Yield: 31 mg; LCMS m / z = 427 [M+H]+; ’H-NMR (400 MHz, DMSO- de): 12.50 (s, 1H), 7.95 (d, 1H), 7.78 (d, 1H), 7.57-7.49 (m, 2H), 7.43 (dd, 1H), 7.26 (dd, 1H), 6.77 (d, 1H), 6.27 (d, 1H), 3.84 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H)

[0850] Example 407-466

[0851] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 403-406.

[0852]

[0853] Example 467-470

[0854] (2-((3-chloro-4-fluorophenyl)((5-chloro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0855] To a solution Intermediate 20 (350 mg, 0.6 mmol, 1.0 equiv.) in DCM (5 mL) were added 5-chloro-6-methylpyr- idin-2-amine (173 mg, 1.21 mmol, 2 equiv.), BF3-OEt2 (0.15 mL, 1.21 mmol, 2 equiv.) and TFA (0.28 mL, 3.64 mmol, 6 equiv.) and stirred at RT for 2 h The reaction mixture was diluted with ice-cold water (50 mL) and extracted with dichloromethane (2 x 50 mL). The combined organic layer were washed with sodium bicarbonate solution (100 ml), brine (100 mL), dried over anhydrous Na2SC>4, filtered and concentrated under reduced pressure to get crude product which was purified by reverse phase prep HPLC to afford crude product which was purified by RP prep HPLC. Stereosisomers were separated by chiral SFC.

[0856] Preparative first chiral SFC: column: Chiralpak IC (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 467 and 468, second eluting: 469, third eluting: 470.

[0857] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm ), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol,, flow: 90 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C. First eluting: 467, second eluting: 468.

[0858] 467: Yield: 2%. LC-MS: m / z [M+H]+= 442.1 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.64-7.61 (m, 2H), 7.42-7.35 (m, 3H), 6.57 (d, J = 8.72 Hz, 1H), 6.27 (d, J = 8.0 Hz, 1H), 3.84 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.29 (s, 3H). 468: Yield: 2%. LC-MS: m / z [M+H]+= 442.1.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.34 (br s, 1H), 7.64-7.61 (m, 2H), 7.42-7.35 (m, 3H), 6.57 (d, J = 8.8 Hz, 1H), 6.27 (d, J = 9.0 Hz, 1H), 3.84 (s, 1H), 2.92 (s, 3H), 2.36 (s, 3H), 2.29 (s, 3H). 469: Yield: 5%. LC-MS: m / z [M+H]+= 442.1. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppml2.47 (s, 1H), 7.65-7.61 (m, 2H), 7.42-7.35 (m, 3H), 6.57 (d, J = 8.72 Hz, 1H), 6.27 (d, J = 7.76 Hz, 1H), 3.84 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.30 (s, 3H). 470: Yield: 5%. LC-MS: m / z [M+H]+= 442.1. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.64-7.61 (m, 2H), 7.42-7.35 (m, 3H), 6.57 (d, J = 8.76 Hz, 1H), 6.27 (d, J = 8.04 Hz, 1H), 3.84 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.30 (s, 3H). Example 417-474

[0859] (2-((3-chloro-4-fluorophenyl)((4-(trifluoromethyl)thiazol-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0860] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0861] Preparative chiral SFC: column: CHIRALPAK IC (30 mm x 250 mm), 5p; co-solvent 0.2% (7N Ammonia in MeOH) in isopropanol, flow: 100 mL / min; % of co-solvent: 15%; ABPR: 100 bar; T: 35 °C.

[0862] 471: 5%, (first eluting). LC-MS: m / z [M+H]+= 468.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.57 (s, 1H), 9.13 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 7.6 Hz, 1H), 7.43-7.41 (m, 3H), 6.11 (d, J = 7.2 Hz, 1H) 3.87 (s, 1 H), 2.96 (s, 3H), 2.37 (s, 3H). 472: 4%, (second eluting). LC-MS: m / z [M+H]+= 468.2. ’H-NMR (400 MHz, DMSO- d6, 25 °C) 5 (ppm)= 12.59 (s, 1H), 9.1 l(s, 1H), 7.66-7.64 (m, 3H), 7.43-7.39(m, 3H), 6.10 (bs, 1 H), 3.89 (s, 1 H), 2.96 (s, 3 H), 2.37 (s, 3H). 473: 4%, (third eluting). LC-MS: m / z [M+H]+= 468.2. ’H-NMR (400 MHz, DMSO- d6, 25 °C) 5 (ppm)= 12.60 (s, 1H), 9.13 (d, J = 6.4 Hz, 1H), 7.66-7.64 (m, 1H), 7.43-7.41 (m, 3H), 6.11 (bs, 1H) 3.88 (s, 1 H), 2.96 (s, 3H), 2.37 (s, 3H). 474: 7%, (forth eluting). LC-MS: m / z [M+H]+= 468.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.57 (s, 1H), 9.12 (s, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.43-7.41 (m, 3H), 6.10 (bs, 1H) 3.88 (s, 1 H), 2.96 (s, 3H), 2.37 (s, 3H).

[0863] Example 475-478

[0864] (2-((3-chloro-4-fluorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imi- dazol-4-yl)(imino)(methyl)-16-sulfanone

[0865] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0866] Preparative first chiral SFC: column: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 120 mL / min; % of co-solvent: 30%; ABPR: 120 bar; T: 35 °C. First eluting: mixture of 475 and 476, second eluting: 477, third eluting: 478. Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in methanol, flow: 120 mL / min; % of co-solvent: 25%; ABPR: 120 bar; T: 35 °C. First eluting: 475, second eluting: 476.

[0867] 475: 4%. LC-MS: m / z [M+H]+= 474.1.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.65-7.63 (m, 1H), 7.52 (d, J = 8.16 Hz, 1H), 7.42-7.35 (m, 2H), 7.26 (d, J = 8.8 Hz, 1H), 7.11-6.74 (m, 1H), 6.55 (d, J = 8.8 Hz, 1H), 6.27 (d, J = 8.04 Hz, 1H), 3.83 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.20 (s, 3H). 476: 4%. LC-MS: m / z [M+H]+= 474.1. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.65-7.63 (m, 1H), 7.52 (d, J = 8.16 Hz, 1H), 7.42-7.35 (m, 2H), 7.26 (d, J = 8.8 Hz, 1H), 7.11-6.74 (m, 1H), 6.55 (d, J = 8.8 Hz, 1H), 6.27 (d, J = 8.04 Hz, 1H), 3.83 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.20 (s, 3H). 477: 4%. LC-MS: m / z [M+H]+= 474.1. ’H- NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.65 (d, J = 6.76 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.42-7.35 (m, 2H), 7.26 (d, J = 8.72 Hz, 1H), 7.12-6.74 (m, 1H), 6.55 (d, J = 8.8 Hz, 1H), 6.27 (d, J = 8.04 Hz, 1H), 3.83 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.21 (s, 3H). 488: 5%. LC-MS: m / z [M+H]+= 474.1. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.65 (d, J = 6.88 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.42-7.37 (m, 2H), 7.26 (d, J = 8.72 Hz, 1H), 7.12-6.74 (m, 1H), 6.55 (d, J = 8.8 Hz, 1H), 6.27 (d, J = 8.04 Hz, 1H), 3.83 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.21 (s, 3H).

[0868] Example 479-482

[0869] (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0870] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereoisomers were separated by chiral SFC.

[0871] Preparative first chiral SFC: column: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 35%; ABPR: 120 bar; T: 35 °C. First eluting: mixture of 479 and 480, second eluting: 481, third eluting: 482.

[0872] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: isopropanol, flow: 90 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 479, second eluting: 480.

[0873] 479: 8%. LC-MS: m / z [M+H]+= 426.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.65-7.63 (m, 1H), 7.42-7.34 (m, 3H), 7.32-7.27 (m, 1H), 6.55-6.52 (m, 1H), 6.24-6.22 (m, 1H), 3.82 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.21-2.20 (m, 3H). 480: 6%. LC-MS: m / z [M+H]+= 426.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.65-7.63 (m, 1H), 7.42-7.27 (m, 4H), 6.55-6.52 (m, 1H), 6.23-6.21 (m, 1H), 3.82 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.21-2.20 (m, 3H). 481: 5%. LC-MS: m / z [M+H]+= 426.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.65-7.63 (m, 1H), 7.42-7.27 (m, 4H), 6.55-6.52 (m, 1H), 6.23-6.21 (m, 1H), 3.84 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.21-2.20 (m, 3H). 482: 8%. LC-MS: m / z [M+H]+= 426.2. ’H- NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.65-7.63 (m, 1H), 7.42-7.27 (m, 4H), 6.55-6.52 (m, 1H), 6.23-6.21 (m, 1H), 3.83 (s, 1 H), 2.95 (s, 3H), 2.36 (s, 3H), 2.21-2.20 (m, 3H). Example 483-486

[0874] 5-chloro-N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-6-(difluo- romethyl)pyridin-2 -amine

[0875] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0876] Preparative first chiral SFC: column: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 120 mL / min; % of co-solvent: 30%; AB PR: 120 bar; T: 35 °C. First eluting: mixture of 483 and 484, second eluting: mixture of 485 and 486.

[0877] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: isopropanol, flow: 120 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 483, second eluting: 484.

[0878] Preparative third chiral SFC: column: I-Cellulose-Z (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 110 mL / min; % of co-solvent: 25%; ABPR: 100 bar; T: 35 °C. First eluting: 485, second eluting: 486.

[0879] 483: LC-MS: m / z [M+H]+= 478.1. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.51 (s, 1H), 8.12-8.10 (d, j= 8.0 Hz, 1H), 7.67-7.61 (m, 2H), 7.43-7.36 (m, 2H), 7.04-6.78 (m, 2H), 6.27-6.22 (m, 2H), 3.86 (s, 1H), 2.96 (s, 3H), 2.32 (s, 3H). 484: LC-MS: m / z [M+H]+= 478.1. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.51 (s, 1H), 8.12-8.10 (d, j= 8.0 Hz, 1H), 7.67-7.61 (m, 2H), 7.43-7.36 (m, 2H), 7.04-6.78 (m, 2H), 6.27-6.22 (m, 2H), 3.86 (s, 1H), 2.96 (s, 3H), 2.32 (s, 3H). 485: LC-MS: m / z [M+H]+= 478.1. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.51 (s, 1H), 8.12-8.10 (d, j= 8.0 Hz, 1H), 7.67-7.61 (m, 2H), 7.43-7.36 (m, 2H), 7.04-6.78 (m, 2H), 6.27-6.22 (m, 2H), 3.86 (s, 1H), 2.96 (s, 3H), 2.32 (s, 3H). 486: LC-MS: m / z [M+H]+= 478.1. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.51 (s, 1H), 8.12-8.10 (d, j= 8.0 Hz, 1H), 7.67-7.61 (m, 2H), 7.43-7.36 (m, 2H), 7.04-6.78 (m, 2H), 6.27-6.22 (m, 2H), 3.86 (s, 1H), 2.96 (s, 3H), 2.32 (s, 3H).

[0880] Example 487-490

[0881] (2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(me- thyl)-16-sulfanone The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereoisomers were separated by chiral SFC.

[0882] Preparative first chiral SFC: column: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 30%; AB PR: 100 bar; T: 35 °C. First eluting: mixture of 487 and 488, second eluting: 489, third eluting: 490.

[0883] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm ), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 30%; AB PR: 100 bar; T: 35 °C. First eluting: 487, second eluting: 488.

[0884] 487: Analytical Chiral HPLC condition: Chiral SFC: column: (R,R)-Whelk-O-1 (4.6 x 150 mm), 3.5 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt = 4.97 min (first eluting). LC-MS: m / z [M+H]+= 408.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.49 (s, 1H), 7.36-7.33 (m, 3H), 7.31-7.27 (m, 2H), 6.56-6.54 (m, 1H), 6.25 (d, J=7.96 Hz, 1H), 3.83 (s, 1H), 2.95 (s, 3H), 2.36 ( s, 3H), 2.21-2.20 (s, 3H). 488: Analytical Chiral HPLC condition: Chiral SFC: column: (R,R)-Whelk-O-1 (4.6 x 150 mm), 3.5 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 3 mL / min; % of co-solvent: 30%; ABPR: 1450 psi; T: 35 °C; Rt 5.80 min (second eluting). LC-MS: m / z [M+H]+= 408.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.49 (s, 1H), 7.38-7.27 (m, 5H), 6.56-6.54 (m, 1H), 6.25 (d, J=8.16 Hz, 1H), 3.84 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.21-2.20 (s, 3H). 489: Analytical Chiral HPLC condition: Chiral SFC: column: Chiralpak IC (4.6 x 150 mm), 3.5 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; T: 35 °C; Rt= 3.72 min (first eluting). LC-MS: m / z [M+H]+= 408.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.44 (s, 1H), 7.47 (s, 1H), 7.35-7.25 (m, 5H), 6.54- 6.52 (m, 1H), 6.23 (d, J=8.12 Hz, 1H), 3.81 (s, 1H), 2.93 (s, 3H), 2.35 ( s, 3H), 2.19-2.18 (m, 3H). 490: Analytical Chiral HPLC condition: Chiral SFC: column Chiralpak IC (4.6 x 150 mm), 3.5 pm, mobile phase 0.5 % isopropylamine in isopropanol; flow: 4 mL / min; % of co-solvent: 40%; T: 35 °C; Rt = 4.37 min (first eluting). LC-MS: m / z [M+H]+= 408.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (s, 1H), 7.48 (s, 1H), 7.35-7.25 (m, 5H), 6.54-6.52 (m, 1H), 6.23 (d, J=7.92 Hz, 1H), 3.81 (s, 1H), 2.93 (s, 3H), 2.35 ( s, 3H), 2.19-2.18 (m, 3H).

[0885] Example 491-494

[0886] (2-((3-chloro-4-fluorophenyl)((5-chloro-4-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0887]

[0888] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0889] Chiral SFC column: CHIRALPAK IH (4.6 x 250 mm), 5 pm, Mobile phase: 90% CO2 + 10% of 0.3% DEA in MeOH; Flow: 3 mL / min; % of Co-solvent: 10%; ABPR: 1500 psi; T: 35 °C; First eluting: 491, second eluting: 492, third eluting: 493, forth eluting 494.

[0890] 491: LC-MS: m / z [M+H]+= 442.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.42 (bs, IH), 7.87 (s, IH), 7.62-7.56 (m, 2H), 7.36-7.31 (m, 2H), 6.66 (s, IH), 6.23 (d, J = 8.04 Hz, IH), 3.79 (bs, IH), 2.92 (s, 3H), 2.34 (s, 3H), 2.16 (s, 3H). 492: LC-MS: m / z [M+H]+= 442.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.48 (bs, IH), 7.90 (s, IH), 7.68-7.56 (m, 2H), 7.38-7.36 (m, 2H), 6.68 (s, IH), 6.25 (d, J = 8.12 Hz, IH), 3.83 (bs, IH), 2.95 (s, 3H), 2.36 (s, 3H), 2.19 (s, 3H). 493: LC-MS: m / z [M+H]+= 442.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.46 (br, IH), 7.90 (s, IH), 7.64-7.56 (m, 2H), 7.39-7.36 (m, 2H), 6.68 (s, IH), 6.26 (d, J = 7.96 Hz, IH), 3.83 (s, IH), 2.94 (s, 3H), 2.37 (s, 3H), 2.19 (s, 3H). 494: LC-MS: m / z [M+H]+= 442.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.47 (br, IH), 7.89 (s, IH), 7.64-7.59 (m, 2H), 7.38-7.36 (m, 2H), 6.68 (s, IH), 6.25 (d, J = 8.04 Hz, IH), 2.96 (s, 3H), 2.37 (s, 3H), 2.19 (s, 3H).

[0891] Example 495-498

[0892] (2-((3-chloro-4-fluorophenyl)((5-chloro-6-cyclopropylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0893] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC. Preparative first chiral SFC: column: column I-Cellulose-C (21 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 60 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 495 and 496, second eluting: 497, third eluting: 498.

[0894] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm ), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: 495, second eluting: 496.

[0895] 495: LC-MS: m / z [M+H]+= 468.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.41 (s, 1H), 7.63-7.56 (m, 2H), 7.40-7.36 (m, 3H), 6.52-6.49 (m, 1H), 5.99 (d, J = 6.36 Hz, 1H), 3.83 (bs, 1H), 2.95 (s, 3H), 2.53 (s, 1H), 2.36 (s, 3H), 2.21-2.17 (m, 1H), 0.84-0.75 (m, 4H), 0.64-0.61 (m, 1H). 496: LC-MS: m / z [M+H]+= 468.2. 'H- NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.42 (s, 1H), 7.62 (d, J = 7.6 Hz, 1H ), 7.57 (d, J = 6.4 Hz, 1H), 7.40-7.36 (m, 3H), 6.52-6.48 (m, 1H), 5.99 (d, J = 6.40 Hz, 1H), 3.80 (s, 1H), 2.95 (s, 3H), 2.53 (s, 1H), 2.36 (s, 3H), 2.20-2.19 (m, 1H), 1.03 (d, J = 6.08 Hz, 1H), 0.84-0.75 (m, 3H), 0.62-0.60 (m, 1H). 497: LC-MS: m / z [M+H]+= 468.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.41 (s, 1H), 7.62 (d, J = 7.08 Hz, 1H ), 7.56 (d, J = 6.4 Hz, 1H), 7.40-7.36 (m, 3H), 6.50 (d, J = 8.88 Hz, 1H), 6.00 (d, J = 6.40 Hz, 1H), 3.79 (s, 1H), 2.95 (s, 3H), 2.32 (s, 3H), 2.20-2.19 (m, 1H), 1.03 (d, J = 6.08 Hz, 1H), 0.84-0.76 (m, 4H), 0.62-0.61 (m, 1H). 498: LC-MS: m / z [M+H]+= 468.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.41 (s, 1H), 7.62 (d, J = 7.48 Hz, 1H ), 7.56 (d, J = 6.36 Hz, 1H), 7.40-7.36 (m, 3H), 6.50 (d, J = 8.80 Hz, 1H), 6.00 (d, J = 6.36 Hz, 1H), 3.81 (s, 1H), 2.96 (s, 3H), 2.32 (s, 3H), 2.21-2.16 (m, 1H), 1.03 (d, J = 6.12 Hz, 1H), 0.84-0.76 (m, 3H), 0.64-0.61 (m, 1H).

[0896] Example 499-502

[0897] (2-((3-chloro-4-fluorophenyl)((3,5-difluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0898] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0899] Preparative first chiral SFC: column: column Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 110 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 499, second eluting: mixture of 500 and 501, third eluting: 502.

[0900] Preparative second chiral SFC: column: I-Cellulose-Z (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 100 mL / min; % of co-solvent: 20%; ABPR: 100 bar; T: 35 °C. First eluting: 500, second eluting: 501.

[0901] 499: LC-MS: m / z [M+H]+= 444.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.37 (bs, 1H), 7.67 (d, J = 6.8 Hz, 1H), 7.6 (t, J = 9.66 Hz, 1H), 7.44-7.43 (m, 1H), 7.39-7.34 (m, 1H), 7.25 (d, J = 7.88 Hz, 1H), 6.37 (d, J = 7.84 Hz, 1H), 3.84 (bs, 1 H), 2.96 (s, 3H), 2.38 (s, 3H), 2.21 (s, 3H). 500: LC-MS: m / z [M+H]+= 444.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.37 (bs, 1H), 7.68-7.66 (m, 1H), 7.63-7.58 (m, 1H), 7.45-7.43 (m, 1H), 7.39-7.34 (m, 1H), 7.25 (d, J = 7.88 Hz, 1H), 6.38 (d, J = 8.16 Hz, 1H), 3.84 (bs, 1 H), 2.96 (s, 3H), 2.38 (s, 3H), 2.21 (s, 3H). 501: LC-MS: m / z [M+H]+= 444.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.37 (bs, 1H), 7.68-7.58 (m, 2H), 7.44-7.43 (m, 1H), 7.39-7.35 (m, 1H), 7.26-7.24 (m, 1H), 6.38 (d, J = 8.16 Hz, 1H), 3.85 (bs, 1 H), 2.96 (s, 3H), 2.38 (s, 3H), 2.21 (s, 3H). 502: LC-MS: m / z [M+H]+= 444.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.37 (bs, 1H), 7.68-7.58 (m, 2H), 7.44-7.43 (m, 1H), 7.39-7.35 (m, 1H), 7.26-7.24 (m, 1H), 6.38 (d, J = 8.16 Hz, 1H), 3.84 (bs, 1 H), 2.96 (s, 3H), 2.38 (s, 3H), 2.21 (s, 3H).

[0902] Example 503-505

[0903] (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-(methyl-d3)pyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0904] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0905] Preparative first chiral SFC: column: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 100 mL / min; % of co-solvent: 35%; ABPR: 100 bar; T: 35 °C. First eluting: 503 (mixture of 2 stereoisomers) second eluting: 504, third eluting: 505.

[0906] 503 (mixture of 2 stereoisomers): LC-MS: m / z [M+H]+= 429.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.44 (s, 1H), 7.65-7.63 (m, 1H), 7.41-7.34 (m, 3H), 7.30 (t, J = 9.04 Hz, 1H), 6.55-6.52 (m, 1H), 6.23 (d, J = 8.12 Hz, 1H), 3.83 (s, 1H), 2.88 (s, 3H), 2.37 (s, 3H), 2.22 (s, 3H). 504: LC-MS: m / z [M+H]+ = 429.2. 1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.64-7.63 (m, 1H), 7.41-7.35 (m, 3H), 7.30 (t, J = 9.04 Hz, 1H), 6.55-6.52 (m, 1H), 6.23 (d, J = 8.12 Hz, 1H), 3.85 (s, 1H), 2.95 (s, 3H), 2.37 (s, 3H), 2.22 (s, 3H). 505: LC-MS: m / z [M+H]+ = 429.2. 1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.44 (s, 1H), 7.64-7.63 (m, 1H), 7.41- 7.35 (m, 3H), 7.30 (t, J = 9.04 Hz, 1H), 6.55-6.52 (m, 1H), 6.23 (d, J = 8.12 Hz, 1H), 3.83 (s, 1H), 2.95 (s, 3H), 2.32 (s, 3H), 2.22 (s, 3H).

[0907] Example 506-509

[0908] N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-5-methyl-4-(trifluo- romethyl)- 1 ,3 -thiazol-2 -amine

[0909] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0910] Preparative chiral SFC: column: CHIRALPAK IC (30 mm x 250 mm), 5p; co-solvent 0.2% (7N Ammonia in MeOH) in isopropanol, flow: 90 mL / min; % of co-solvent: 25%; ABPR: 100 bar; T: 35 °C. First eluting: 506, second eluting: 507, third eluting: 508, forth eluting 509.

[0911] 506: 13%. LC-MS: m / z [M+H]+= 482.2. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.55 (s, 1H), 8.85 (d, J = 7.96 Hz, 1H), 7.63 (d, J= 7.68 Hz, 1H), 7.40-7.42 (m, 2H), 6.03 (d, J = 7.96 Hz, 1H), 3.89 (s, 1H), 2.95 (s, 3H), 2.37(s, 3H), 2.30 (singlets, 3H). 507: 4%. LC-MS: m / z [M+H]+= 482.2.. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.55 (s, 1H), 8.84 (d, J = 8 Hz, 1H), 7.63 (d, J= 6.92 Hz, 1H), 7.40-7.42 (m, 2H), 6.03 (d, J = 8 Hz, 1H), 2.95 (s, 3H), 2.37(s, 3H), 2.30 (singlets, 3H). 508: 4%. LC-MS: m / z [M+H]+= 488.2.1H-NMR (400 MHz, DMSO- d6, 25 °C) 5 (ppm)= 12.55 (s, 1H), 8.85 (d, J = 7.96 Hz, 1H), 7.63 (d, J= 7.68 Hz, 1H), 7.40-7.42 (m, 2H), 6.03 (d, J = 7.96 Hz, 1H), 3.89 (s, 1H), 2.95 (s, 3H), 2.37(s, 3H), 2.30 (singlets, 3H). 509: 7%. LC-MS: m / z [M+H]+= 488.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.55 (s, 1H), 8.85 (d, J = 7.96 Hz, 1H), 7.63 (d, J= 7.68 Hz, 1H), 7.40-7.42 (m, 2H), 6.03 (d, J = 7.96 Hz, 1H), 3.89 (s, 1H), 2.95 (s, 3H), 2.37(s, 3H), 2.30 (singlets, 3H).

[0912] Example 510-513

[0913] (2-((3 -chloro-4-fluorophenyl)((6-( 1 , 1 -difluoroethyl)-5-fluoropyridin-2-yl)amino)methyl)-5-methyl- IH-imidazol- 4-yl)(imino)(methyl)-16-sulfanone

[0914] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0915] Preparative first chiral SFC: column: column: I-Cellulose-C (21 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 70 mL / min; % of co-solvent: 40%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 510 and 511, second eluting: mixture of 512 and 513.

[0916] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 90 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 510, second eluting: 511.

[0917] Preparative third chiral SFC: column: ChiralPak IG (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in hexane-isopropanol (1:1), flow: 90 mL / min; % of co-solvent: 25%; ABPR: 100 bar; T: 35 °C. First eluting: 512, second eluting: 513.

[0918] 510: LC-MS: m / z [M+H]+= 476.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.51 (s, 1H), 7.8 (d, J = 6.72 Hz, 1H), 7.68 (d, J = 7.12 Hz, 1H), 7.53 (t, J = 9.68 Hz, 1H), 7.44-7.37 (m, 2H), 6.90 (d, J = 8.0 Hz, 1H), 6.09 (d, J = 6.76 Hz, 1H), 3.82 (bs, 1 H), 2.94 (s, 3H), 2.37-2.32 (m, 3H), 1.88-1.78 (m, 3H). 511: LC-MS: m / z [M+H]+= 476.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.79 (d, J = 6.52 Hz, 1H), 7.68 (d, J = 6.92 Hz, 1H), 7.53 (t, J = 9.68 Hz, 1H), 7.44-7.38 (m, 2H), 6.90 (d, J = 8.68 Hz, 1H), 6.09 (d, J = 6.56 Hz, 1H), 3.81 (bs, 1 H), 2.94 (s, 3H), 2.37-2.32 (m, 3H), 1.88-1.78 (m, 3H). 512: LC-MS: m / z [M+H]+= 476.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.8 (d, J = 6.68 Hz, 1H), 7.68 (d, J = 6.76 Hz, 1H), 7.53 (t, J = 9.68 Hz, 1H), 7.44-7.37 (m, 2H), 6.90 (d, J = 8.76 Hz, 1H), 6.09 (d, J = 6.68 Hz, 1H), 3.87 (bs, 1 H), 2.95 (s, 3H), 2.37-2.29 (m, 3H), 1.88-1.78 (m, 3H). 513: LC-MS: m / z [M+H]+= 476.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.47 (s, 1H), 7.8 (d, J = 6.64 Hz, 1H), 7.68 (d, J = 6.6 Hz, 1H), 7.53 (t, J = 9.68 Hz, 1H), 7.44- 7.37 (m, 2H), 6.90 (d, J = 8.8 Hz, 1H), 6.09 (d, J = 6.64 Hz, 1H), 3.87 (bs, 1 H), 2.95 (s, 3H), 2.37-2.32 (m, 3H), 1.88-1.78 (m, 3H). Example 514-517

[0919] (2-((3-chloro-4-fluorophenyl)((6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(me- thyl)-16-sulfanone

[0920] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC.

[0921] Preparative chiral SFC: column: column: Chiralpak IC (30 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 120 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 514 and 515, second eluting: 516, third eluting: 517.

[0922] Preparative second chiral SFC: column: I Cellulose Z (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (1:1), flow: 90 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 514, second eluting: 515.

[0923] 514: 13%, LC-MS: m / z [M+H]+= 408.2.1H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.55 (s, 1H), 8.85 (d, J = 7.96 Hz, 1H), 7.63 (d, J= 7.68 Hz, 1H), 7.40-7.42 (m, 2H), 6.03 (d, J = 7.96 Hz, 1H), 3.89 (s, 1H), 2.95 (s, 3H), 2.37(s, 3H), 2.30 (singlets, 3H). 515: 4%, LC-MS: m / z [M+H]+= 408.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.55 (s, 1H), 8.84 (d, J = 8 Hz, 1H), 7.63 (d, J= 6.92 Hz, 1H), 7.40-7.42 (m, 2H), 6.03 (d, J = 8 Hz, 1H), 2.95 (s, 3H), 2.37(s, 3H), 2.30 (singlets, 3H). 516: 4%, LC-MS: m / z [M+H]+= 408.2. ’H-NMR (400 MHz, DMSO- d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.64 (d, J = 7.12 Hz, 1H), 7.42-7.28 (m, 4H), 6.47 (d, J = 8.04 Hz, 1H), 6.41 (d, J = 6.76 Hz, 1H), 6.34 (d, J = 7.76 Hz, 1H), 3.91-3.86 (m, 1H), 2.96 (s, 3H), 2.32 (s, 3H), 2.22 (s, 3H). 517: 7%, LC-MS: m / z [M+H]+= 408.2. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.45 (s, 1H), 7.64 (d, J = 7.12 Hz, 1H), 7.42-7.27 (m, 4H), 6.47 (d, J = 8.04 Hz, 1H), 6.41 (d, J = 6.76 Hz, 1H), 6.34 (d, J = 7.76 Hz, 1H), 3.93-3.87 (m, 1H), 2.96 (s, 3H), 2.32 (s, 3H), 2.22 (s, 3H).

[0924] Example 518-521

[0925] (2-(((5-fluoro-6-methylpyridin-2-yl)amino)(4-(trifluoromethyl)phenyl)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0926] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by chiral SFC. Preparative first chiral SFC: column: column: I Cellulose C (21.1 mm><250 mm), 5p; co-solvent: isopropanol, flow: 60 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: mixture of 518 and 519, second eluting: mixture of 520 and 521.

[0927] Preparative second chiral SFC: column: (R,R)-Whelk-O-1 (30 mm x 250 mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in isopropanol, flow: 110 mL / min; % of co-solvent: 30%; ABPR: 100 bar; T: 35 °C. First eluting: 519, second eluting: 520.

[0928] Preparative third chiral SFC: column: column: I Cellulose C (21 mm x 250mm), 5p; co-solvent: 0.2% (7N ammonia in methanol) in acetonitrile-isopropanol (7:3), flow: 70 mL / min; % of co-solvent: 25%; ABPR: 100 bar; T: 35 °C. First eluting: 521, second eluting: 522.

[0929] 520: LC-MS: m / z [M+H]+= 442.3. 'H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.5 (s, 1H), 7.70 (d, J=8.2 Hz, 2H), 7.62 (d, J=8.12Hz, 2H), 7.42 (d, J=8.08 Hz, 1H), 7.29 (t, J=9.08 Hz, 1H), 6.57-6.54 (m,lH), 6.33 (d, J=8.16 Hz, 1H), 3.82 (s, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.20-2.19 (m, 3H). 520: LC-MS: m / z [M+H]+= 442.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.5 (s, 1H), 7.70 (d, J=8.2 Hz, 2H), 7.62 (d, J=8.12Hz, 2H), 7.42 (d, J=8.08 Hz, 1H), 7.29 (t, J=9.08 Hz, 1H), 6.57-6.54 (m,lH), 6.33 (d, J=8.16 Hz, 1H), 3.82 (s, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.20-2.19 (m, 3H). 520: LC-MS: m / z [M+H]+= 442.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.5 (s, 1H), 7.70 (d, J=8.2 Hz, 2H), 7.62 (d, J=8.12Hz, 2H), 7.42 (d, J=8.08 Hz, 1H), 7.29 (t, J=9.08 Hz, 1H), 6.57-6.54 (m,lH), 6.33 (d, J=8.16 Hz, 1H), 3.82 (s, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.20-2.19 (m, 3H). 520: LC-MS: m / z [M+H]+= 442.3. ’H-NMR (400 MHz, DMSO-d6, 25 °C) 5 (ppm)= 12.5 (s, 1H), 7.70 (d, J=8.2 Hz, 2H), 7.62 (d, J=8.12Hz, 2H), 7.42 (d, J=8.08 Hz, 1H), 7.29 (t, J=9.08 Hz, 1H), 6.57-6.54 (m,lH), 6.33 (d, J=8.16 Hz, 1H), 3.82 (s, 1H), 2.95 ( s, 3H), 2.37 (s, 3H), 2.20-2.19 (m, 3H).

[0930] Example 522-525

[0931] (2-((3,4-dichlorophenyl)((5-fluoro-4-methylpyrimidin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone

[0932] The title compounds were prepared from the appropriate intermediates and reagents using an analogous method to that described for Example 467-470. Stereosiomers were separated by c...

Claims

CLAIMS1. A compound according to general formula (I)whereinLi represents O, C(R7)2-O, O-C(R7)2, N(R7), C(R7)2-N(R7), N(R7)-C(R7)2, S, C(R7)2-S, S-C(R7)2, C(R7)2, or C(R7)2C(R7)2;A and B independently from one another represent phenyl, 5- to 10-membered heteroaryl, Ci-6-alkyl,cycloalkyl, or 4- to 10-membered heterocycloalkyl;R2and R3 independently from one another represent F, Cl, Br, CN, Ci-6-alkyl, C>, -e-cycloalky I. NH2, N(H)Ci-4-alkyl, N(Ci.4-alkyl)2, OH, O-Ci.4-alkyl, O-C3-6-cycloalkyl, SF5, phenyl or C3.e-cycloal- kyl; x and y independently from one another represent 0, 1, 2, 3, or 4;R4represents H, Cl, CN, Ci-e-alkyl, or C3-6-cycloalkyl;L2represents bond, Ci-3-alkylene, or Ci-2-alkylene-N(H); andRs represents S(=O)Re, S(=O)(=NH)R6, S(=O)2Re or S(=O)2NH2;Re represents Ci-e-alkyl;R7represents H, or Ci.4-alkyl; wherein Ci-e-alkyl, Ci.4-alkyl, Ci.4-alkylene, Ci.3-alkylene and Ci.2-alkylene in each case independently from one another is linear or branched, saturated or unsaturated; wherein Ci -e-alkyl, Ci-4-alkyl, Ci-4-alkylene, Ci-3-alkylene, Ci-2-alkylene, C3.io-cycloalkyl, C3.7-cycloalkyl, C3-e-cycloalkyl, C5-7-cycloalkyl, 4- to 10- membered heterocycloalkyl, and 4- to 7- membered heterocycloalkyl in each case independently from one another are unsubstituted or mono- or polysubstituted with one or more substituents selected from F; Cl; CN; Ci-e-alkyl; CF3; CF2H; CFH2; OH; =0; OCF3; OCF2H; OCFH2; O-Ci-6-alkyl; NH2; N(H)(Ci-6-alkyl); N(Ci.6-alkyl)2; SCF3; SCF2H; SCFH2; and S-Ci.6-alkyl; wherein phenyl, 5- to 10-membered heteroaryl and 5 or 6-membered heteroaryl in each case independently from one another are unsubstituted or mono- or poly substituted with one or more substituents selected from F; Cl; CN; Ci-6-alkyl; CF3; CF2H; CFH2; OH; OCF3; OCF2H; OCFH2; O-Ci-6-alkyl; NH2; N(H)(Ci-6-alkyl); and N(Ci-6-alkyl)2; in the form of the free compound or a physiologically acceptable salt thereof.

2. The compound according to claim 1, wherein R4represents H, or Ci -e-alkyl.

3. The compound according to claim 1 or 2, whereinx and y independently from one another represent 0, 1, 2 or 3.

4. The compound according to any of the preceding claims, wherein at least one of A and B represents phenyl or 5- or 6-membered heteroaryl.

5. The compound according to any of the preceding claims, wherein A represents phenyl or 5- or 6-membered heteroaryl.

6. The compound according to any of the preceding claims, wherein Li represents O, O-C(R7)3, N(R7), S, or C(R7)2.

7. The compound according to any of the preceding claims, wherein R7represents H or methyl.

8. The compound according to any of the preceding claims, whereinR2 represents F, Cl, CN, Ci-6-alkyl, or O-Ci-4-alkyl.

9. The compound according to claim 8, wherein x represents 2.

10. The compound according to any of the preceding claims, whereinR3represents F, Cl, Br, OH, CN, Ci.6-alkyl, O-Ci.4-alkyl, O-C3-6-cycloalkyl, SF5, phenyl or C3.6-cycloalkyl.

11. The compound according to any of the preceding claims, wherein L2represents bond.

12. The compound according to any of the preceding claims, wherein R6represents methyl or 2-propyl.

13. The compound according to any of the preceding claims selected from the group consisting of1 2-((3 -chloro-4-fluorophenyl)(methoxy)methyl)-4-(methylsulfonyl)- IH-imidazole2 2-((3 -chloro-4-fluorophenyl)(isopropoxy)methyl)-4-(methylsulfonyl)- IH-imidazole3 2-((3-chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-4-(methylsulfonyl)-lH-imidazole4 2-((3-chloro-4-fluorophenyl)(cyclobutoxy)methyl)-4-(methylsulfonyl)-lH-imidazole5-6 2-((3-chloro-4-fluorophenyl)((4,4-difluorocyclohexyl)oxy)methyl)-4-(methylsulfonyl)-IH-imidazole7 2-((3 -chloro-4-fluorophenyl)(phenoxy)methyl)-4-(methylsulfonyl)- IH-imidazole8 2-((3 -chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-4-(methylsulfonyl)- IH-imidazole9-10 2-((3-chloro-4-fluorophenyl)(4-fluoro-2-methoxyphenoxy)methyl)-5-(methylsulfonyl)-IH-imidazole11 2-((3-chloro-4-fluorophenyl)(3-methoxyphenoxy)methyl)-4-methyl-5-(methylsulfonyl)- IH-imidazole12 2-((3-chloro-4-fluorophenyl)(3,4-difluorophenoxy)methyl)-4-methyl-5-(methylsul- fonyl)- IH-imidazole13 2-((3-chloro-4-fluorophenyl)(4-methoxyphenoxy)methyl)-4-methyl-5-(methylsulfonyl)-IH-imidazole2-((3-chloro-4-fluorophenyl)(4-fluoro-2-methylphenoxy)methyl)-4-methyl-5-(methyl- sulfonyl)- IH-imidazole -16 2-((3-chloro-4-fluorophenyl)(((cis)-4-methylcyclohexyl)oxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole -18 2-((3-chloro-4-fluorophenyl)(((trans)-4-methylcyclohexyl)oxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole -20 2-((3-chloro-4-fluorophenyl)((l-methylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole2-((benzyloxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole2-((3-chloro-4-fluorophenyl)((lr,3r)-3-fluorocyclobutoxy)methyl)-5-methyl-4-(methyl- sulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)(cyclopropylmethoxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)(((2S,3S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)oxy)me- thyl)-5-methyl-4-(methylsulfonyl)-lH-imidazole2-((3-chloro-4-fluorophenyl)((4-ethylcyclohexyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)((2,3-dihydro-lH-inden-2-yl)oxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)((4,4-dimethylcyclohexyl)oxy)methyl)-5-methyl-4-(methyl- sulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)(cyclopentyloxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole2-((3-chloro-4-fluorophenyl)(cyclobutylmethoxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)((3,3-difluorocyclobutyl)methoxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)(3-(difluoromethyl)cyclobutoxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)(3-(trifluoromethyl)cyclobutoxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)(3,3-difluorocyclobutoxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)((2,2-difluorocyclopentyl)oxy)methyl)-5-methyl-4-(methyl- sulfonyl)- IH-imidazole2-((bicyclo[3.1.0]hexan-3-yloxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(methyl- sulfonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)(l-(4-fluorophenyl)ethoxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)((l-methylcyclopentyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -39 2-((3-chloro-4-fluorophenyl)((4-fluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole -41 2-((3-chloro-4-fluorophenyl)(l-methylcyclobutoxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -43 2-((3-chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-5-methyl-4-(methylsulfonyl)-lH- imidazole -45 2-((3-chloro-4-fluorophenyl)((3-fluorobenzyl)oxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole-47 2-((3 -chloro-4-fluorophenyl)((3 ,3 -difluoro- 1 -methylcyclobutyl)methoxy)methyl)-5-me- thyl-4-(methylsulfonyl)-lH-imidazole 3-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thoxy)methyl)pyridine -50 5-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thoxy)methyl)-4-methylthiazole 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thoxy)methyl)pyridine -53 2-((3-chloro-4-fluorophenyl)((5,6-difluoro-2,3-dihydro-lH-inden-2-yl)oxy)methyl)-5- methyl-4-(methylsulfonyl)-lH-imidazole -55 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thoxy)methyl)-5 -methylthiazole -57 2-((3-chloro-4-fluorophenyl)((3,5-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -59 2-(((4-chloro-3-fluorobenzyl)oxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole -61 2-((3-chloro-4-fluorophenyl)((2,5-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -63 2-((3-chloro-4-fluorophenyl)((2,3-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -65 2-((3-chloro-4-fluorophenyl)((2,4-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -67 2-(((2-chloro-4-fluorobenzyl)oxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole -69 2-((3-chloro-4-fluorophenyl)((3-chlorobenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -71 2-((3-chloro-4-fluorophenyl)((4-chlorobenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -73 2-((3-chloro-4-fluorophenyl)((3,4-difluoroben-zyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -75 2-((3-chloro-4-fluorophenyl)((2,6-difluorobenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole -77 2-(((3-chloro-4-fluorobenzyl)oxy)(3-chloro-4-fluorophenyl)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole -79 2-((3-chloro-4-fluorophenyl)((4-(trifluoromethyl)benzyl)oxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole -81 2-((3-chloro-4-fluorophenyl)((3-(trifluoromethyl)benzyl)oxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole -83 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thoxy)methyl)-6-(trifluoromethyl)pyridine -85 2-[(3-chloro-4-fluorophenyl)({[(trans)-4-methoxycyclohexyl]oxy})methyl]-4-methane- sulfony 1-5 -methyl- IH-imidazole -87 2-[(3-chloro-4-fluorophenyl)({spiro[2.3]hexan-5-yloxy})methyl]-4-methanesulfonyl-5- methyl- IH-imidazole -89 2-[(3-chloro-4-fluorophenyl)({spiro[3.3]heptan-2-yloxy})methyl]-4-methanesulfonyl-5- methyl- IH-imidazole -91 2-((3-chloro-4-fluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-me- thyl-4-(methylsulfonyl)-lH-imidazole -93 2-((3-chloro-4-fluorophenyl)((3-(trifluoromethoxy)benzyl)oxy)methyl)-5-methyl-4-(me- thylsulfonyl)- IH-imidazole-95 2-((3-chloro-4-fluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)methoxy)methyl)-5- methyl-4-(methylsulfonyl)-lH-imidazole -97 2-((3-chloro-4-fluorophenyl)(((S)-3,3-difluorocyclopentyl)methoxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole -99 2-((3-chloro-4-fluorophenyl)(((R)-3,3-difluorocyclopentyl)methoxy)methyl)-5-methyl-4-(methylsulfonyl)- IH-imidazole 0-101 2-[(3-chloro-4-fluorophenyl)({[(cis)-4-methoxycyclohexyl]oxy})methyl]-4-methanesul- fony 1-5 -methyl- IH-imidazole 4-105 2-((3-chloro-4-fluorophenyl)(((cis)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-me- thyl-4-(methylsulfonyl)-lH-imidazole 6-107 2-((3-chloro-4-fluorophenyl)((4-methylbenzyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole 8-109 3-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thoxy)methyl)-2-methyl-6-(trifluoromethyl)pyridine 0 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclobutyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole 1 2-[(3-chloro-4-fluorophenyl)-(5-oxaspiro[2.4]heptan-2-ylmethoxy)methyl]-5-methyl-4- methylsulfonyl- IH-imidazole 2 2-[(3-chloro-4-fluorophenyl)-[(3,3-dimethylcyclobutyl)methoxy]methyl]-5-methyl-4- methylsulfonyl-lH-imidazole 3 2-[(3 -chloro-4-fhiorophenyl)-(3 ,3 -dimethylcyclohexyl)oxymethyl] -5-methyl-4-methyl- sulfonyl- IH-imidazole 4 2-[(3-chloro-4-fluorophenyl)-[(4,4-dimethyloxolan-2-yl)methoxy]methyl]-5-methyl-4- methylsulfonyl-lH-imidazole 5 2-[(3-chloro-4-fluorophenyl)-[(3-methyl-3-bicyclo[3.1.0]hexanyl)methoxy]methyl]-5- methyl-4-methylsulfonyl-lH-imidazole 6 2-[(3-chloro-4-fluorophenyl)-[(l-methylcyclobutyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole 7 2-[(3-chloro-4-fluorophenyl)-(2-cyclopropyl-2,2-difluoroethoxy)methyl]-5-methyl-4- methylsulfonyl- IH-imidazole 8 2-[(3-chloro-4-fluorophenyl)-[(2-fluoro-l-methylcyclopropyl)methoxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole 9 2-[(3-chloro-4-fluorophenyl)-(spiro[2.3]hexan-5-ylmethoxy)methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole 0 2-[(3-chloro-4-fluorophenyl)-[(l-propan-2-ylcyclopropyl)methoxy]methyl]-4-methyl-5- methylsulfonyl-lH-imidazole 1 2-[3-bicyclo[4.1.0]heptanylmethoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole 2 2-[(3-chloro-4-fluorophenyl)-spiro[2.3]hexan-6-yloxymethyl]-5-methyl-4-methylsul- fonyl- IH-imidazole 3 2-[(3-chloro-4-fluorophenyl)-[(l-cyclopropylcyclopropyl)methoxy]methyl]-5-methyl-4- methylsulfonyl-lH-imidazole 4 2-[(3-chloro-4-fluorophenyl)-[(3-methyl-l-bicyclo[l.l.l]pentanyl)methoxy]methyl]-5- methyl-4-methylsulfonyl-lH-imidazole 5 2-[(3-chloro-4-fluorophenyl)-(3,3-difluorocyclopentyl)oxymethyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole 6 2-[(3-chloro-4-fluorophenyl)-[3-(trifluoromethyl)cyclohexyl]oxymethyl]-5-methyl-4- methylsulfonyl-lH-imidazole 7 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclohexyl)methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(l-phenylcyclopropyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-(2,3-dihydro-lH-inden-2-ylmethoxy)methyl]-5-methyl-4- methylsulfonyl-lH-imidazole2- [ 1 -bicyclo [2.1.1 ] hexany lmethoxy-(3 -chloro-4-fluoropheny l)methy 1] -5 -methy 1-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-(3-cyclopropylcyclobutyl)oxymethyl]-5-methyl-4-methyl- sulfonyl- IH-imidazole2-[2-bicyclo[4.1.0]heptanylmethoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-tert-butylcyclobutyl)oxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(3-cyclopropylcyclobutyl)methoxy]methyl]-5-methyl-4- methylsulfonyl-lH-imidazole3-chloro-5-[[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- yl)methoxy]methyl] - 1 ,2-oxazole2-[(3-chloro-4-fluorophenyl)-[rac-(2R,4R)-2-methyloxan-4-yl]oxymethyl]-4-methyl-5- methylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[rac-(lR,2S)-2-(trifluoromethyl)cyclopropyl]me- thoxy]methyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[[(lS)-2,2-dimethylcyclopropyl]methoxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole2-[l-bicyclo[2.2.1]heptanylmethoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[(2R,3R)-2,3-dimethylcyclopropyl]methoxy]methyl]-4- methy 1-5 -methy Isulfony 1- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(l-methyl-2-oxabicyclo[2.1.1]hexan-4-yl)methoxy]me- thyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(2-tert-butylcyclopropyl)methoxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-(2,2-difluorospiro[2.3]hexan-5-yl)oxymethyl]-5-methyl-4- methylsulfonyl-lH-imidazole2-[(3 -chloro-4-fluorophenyl)-[(3 -ethyl- 1 -bicyclo [1.

1. l]pentanyl)oxy]methyl] -4-methyl-5 -methy Isulfony 1- IH-imidazole2-[(3-chloro-4-fluorophenyl)-(2,2-difluorospiro[3.3]heptan-6-yl)oxymethyl]-5-methyl-4- methylsulfonyl-lH-imidazole2-[(3 -chloro-4-fluorophenyl)-[(3 -propan-2 -yl- 1 -bicyclo [1.

1. l]pentanyl)oxy]methyl] -4- methy 1-5 -methy Isulfony 1- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[(lR,2R)-2-(4-fluorophenyl)cyclopropyl]methoxy]me- thyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(2-phenylcyclopropyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[l-(4-fluorophenyl)cyclopropyl]methoxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[[3-(l,l-difluoroethyl)-l-bicyclo[l.l. l]pentanyl]oxy]me- thyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(3-phenylcyclobutyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[3-(trifluoromethyl)cyclopentyl]oxymethyl]-5-methyl-4- methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(4,4-difluorocyclohexyl)methoxy]methyl]-5-methyl-4- methylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[4-(difluoromethyl)cyclohexyl]oxymethyl]-5-methyl-4- methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[3-(2,2,2-trifluoroethyl)cyclobutyl]oxymethyl]-5-methyl-4-methylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-(2-oxaspiro[3.4]octan-6-yloxy)methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[3-(trifluoromethyl)cyclobutyl]methoxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(lS,2S)-2-fluorocyclopentyl]oxymethyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[rac-(lR,2R)-2-methylcyclobutyl]methoxy]methyl]-4-me- thy 1-5 -methylsulfonyl- IH-imidazole2-((3-chloro-4-fluorophenyl)((2-(difluoromethyl)cyclopropyl)methoxy)methyl)-5-me- thyl-4-(methylsulfonyl)-lH-imidazole2-[l-bicyclo[2.2.2]octanyloxy-(3-chloro-4-fluorophenyl)methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole -163 2-[(3-chloro-4-fluorophenyl)-(3-pentylcyclobutyl)oxymethyl]-4-methyl-5-methylsul- fonyl- IH-imidazole2-[[(lS,5S,6R)-6-bicyclo[3.2.0]heptanyl]oxy-(3-chloro-4-fluorophenyl)methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole1-[2-[[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)me- thoxy]methyl]phenyl]-N,N-dimethylmethanamine2-[(3-chloro-4-fluorophenyl)-[(3-methylphenyl)methoxy]methyl]-4-methyl-5-methylsul- fonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(4-methylphenyl)methoxy]methyl]-4-methyl-5-methylsul- fonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(2-methylphenyl)methoxy]methyl]-4-methyl-5-methylsul- fonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[l-(difluoromethyl)cyclopropyl]methoxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(4-fluorocyclohexyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole3-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thoxy]thietane 1,1 -dioxide2-[(3-chloro-4-fluorophenyl)-[3-(methylsulfanylmethyl)cyclobutyl]oxymethyl]-4-me- thy 1-5 -methylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[[(lR,2R,4R)-5,5-difluoro-2-bicyclo[2.2.1]hep- tanyl]oxy]methyl]-5-methyl-4-methylsulfonyl-lH-imidazole5-[[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)me- thoxy] methyl] -3 -methyl- 1 ,2-thiazole3-[[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thoxy] methyl] cyclobutane- 1 -carbonitrile2-[(3-chloro-4-fluorophenyl)-[[4-(trifluoromethyl)-2-oxabicyclo[2.1.1]hexan-l-yl]me- thoxy]methyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[[l-(trifluoromethyl)-2-oxabicyclo[2.1.1]hexan-4-yl]me- thoxy]methyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(3 -chloro-4-fluorophenyl)-[[3 -(trifluoromethyl)- 1 -bicyclo [1.

1. l]pentanyl]me- thoxy]methyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(3 -chloro-4-fluorophenyl)-[(3 ,3 -difluoro- 1 -methy lcyclobutyl)methoxy]methyl] -5-me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[[l-(l,l-difluoroethyl)cyclobutyl]methoxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(l-ethynylcyclopropyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-(2,2-dimethyloxan-4-yl)oxymethyl]-5-methyl-4-methylsul- fonyl- IH-imidazole4-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thoxy ] cyclohexane- 1 -carbonitrile2- [(3 -chloro-4-fluoropheny 1)- [ [ 1 -(trifluoromethy l)cy clopropy 1] methoxy] methyl] -5 -me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[[l-(2,2-difluoroethyl)cyclopropyl]methoxy]methyl]-5- methyl-4-methylsulfonyl-lH-imidazole2-[(3 -chloro-4-fluorophenyl)-[ 1 -(3 -chloro-4-fluorophenyl)ethoxy]methyl] -4-methyl-5- methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(l-methylcyclopropyl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2- [(3 -chloro-4-fluoropheny 1)- [ [ 1 -methy 1-3 -(trifluoromethy l)cy clobuty 1] methoxy] me- thyl]-5-methyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(lR,2R)-2-fluorocyclopentyl]oxymethyl]-5-methyl-4-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(3-fluoro-3-methylcyclobutyl)methoxy]methyl]-5-methyl-4-methylsulfonyl- IH-imidazole2- [(3 -chloro-4-fluoropheny 1)- [ [ 1 -(fluoro methy l)cy clopropy 1] methoxy] methyl] -5 -methy 1-4-methylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(3-fluoro-l-bicyclo[l. l.l]pentanyl)methoxy]methyl]-5- methyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-spiro[2.5]octan-6-yloxymethyl]-5-methyl-4-methylsul- fonyl- IH-imidazole[4-[[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)me- thoxy ]methyl]phenyl]-pentafluoro-Z6-sulfane2-[(3-chloro-4-fluorophenyl)-(4-fluoro-3-methylphenoxy)methyl]-4-methyl-5-methyl- sulfonyl- IH-imidazole ,219,220 N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-fluoroani- line -198 4-chloro-N-((3 -chloro-4-fluorophenyl) (4-(methylsulfonyl)- lH-imidazol-2-yl) me- thyl)aniline -200 5-chloro-N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)py- ridin-2 -amine -202 5-chloro-N-((5-chlorothiophen-2-yl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)pyridin-2 -amine -204 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-6-methylpyridin-2 -amine -206 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trifluoromethyl)pyridin-2 -amine -208 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3,5-difluoropyridin-2-amine -210 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-4-(trifluoromethyl)pyridin-2 -amine-212 5-bromo-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)pyridin-2 -amine -214 N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4,4-diflu- orocy clohexan- 1 -amine -216 3-chloro-N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)aniline -218 N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-fluoropy- ridin-2 -amine N-((3 -chloro-4-fluorophenyl)(4-(methylsulfonyl)- lH-imidazol-2-yl)methyl)-4-fluoro-N- methylaniline 3-chloro-N-((3-chloro-4-fluorophenyl)(4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-N- methylaniline -224 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-3 -metho xypyridin-2 -amine -226 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3- fluoro-5-methylpyridin-2-amine -228 2-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)amino)phenol -230 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6- methy Ipy ridazin-3 -amine -232 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)pyridin-2 -amine -234 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(difluoromethoxy )pyridin-2 -amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)thiazol-2 -amine -237 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-2- fluoro-4-methylaniline -239 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-(trifluo ro methy l)pyridin-3 -amine -241 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)pyrimidin-2 -amine -243 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- fluoropyrimidin-2 -amine -245 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- ethoxypyrimidin-2 -amine -247 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- fluoropyridin-2 -amine -249 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-(difluoromethyl)-5-fluoropyridin-2-amine -251 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)benzo [d]thiazol-2 -amine -253 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-(trifluoromethyl)thiazol-2 -amine -255 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thy l)isoquinolin-3 -amine 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-6-(difluoromethyl)pyridin-2-amine -258 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4-(trifluoromethyl)aniline-260 4,5-dichloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)pyridin-2 -amine -262 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-2- fluoro-4-methoxy aniline -264 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-6-(trifluoromethyl)pyridin-2 -amine -266 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)pyridin-2 -amine -268 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- methoxypyridin-2 -amine -270 5-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-3 -fluoropyridin-2 -amine -272 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- ethoxypyridin-2 -amine -274 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trifluoromethoxy )pyridin-2 -amine -276 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trifluoromethyl)pyrazin-2 -amine -278 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6-(trifluoromethy l)pyridazin-3 -amine -280 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5-(trifluoromethyl)pyrimidin-2 -amine -282 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- cyclopropyl-3 -fluoropyridin-2 -amine -284 3-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-5 -fluoropyridin-2 -amine -286 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3-(trifluoromethyl)aniline -288 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- fluoro-3 -methylpyridin-2-amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-6- methyl-5-(trifluoromethyl)pyrazin-2 -amine 4-(((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)me- thyl)amino)-2-methylpyrimidine-5-carbonitrile -293 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-5- fluoro-6-methylpyridin-2-amine -295 N-[(3-chloro-4-fluorophenyl)(4-methanesulfonyl-5-methyl-lH-imidazol-2-yl)methyl]-5- fluoro-4-methylpyridin-2-amine 4-chloro-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-6-isopropylpyrimidin-2 -amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-4,6-dimethylpyrimidin-2-amine 5-bromo-N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2- yl)methyl)thiazol-2 -amine N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfonyl)-lH-imidazol-2-yl)methyl)-3- cyclopropy 1-5 -fluoropyridin-2 -amine N-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-6- methy 1-5 -(trifluoro methy l)py ridin-3 -amine N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-2- (trifluoromethy l)pyridin-3 -amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-5- methyl-6-(trifluoromethyl)pyridin-3-amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-5- methyl-2-(trifluoromethyl)pyridin-3-amine5-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- y l)methy 1] -6-fluoropy ridin-3 -amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-4- methyl-6-(trifluoromethyl)pyridin-3-amine3-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- y l)methy 1] -5 -fluoropyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-(difluoromethyl)py ridin-3 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-2-(trifluoro methyl)quinolin-3 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(trifluoromethy l)pyridin-3 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-(trifluoromethy l)pyridin-3 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3- fluoro-6-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5- fluoro-4-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5- fluoro-3-(trifluoromethyl)pyridin-2 -amine5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- yl)methyl]-6-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5- fluoro-6-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6- fluoro-3 -(trifluoromethyl)isoquinolin- 1 -amine3-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- yl)methyl]-6-fluoropyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4- fluoro-6-(trifluoromethyl)pyridin-3-amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(trifluoromethyl)quinolin-2-amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5- fluoro-6-(trifluoromethyl)pyridin-3-amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(trifluoromethy l)isoquinolin- 1 -amine4-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- y l)methy 1] -3 -fluoropyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(difluoromethy l)py ridin-3 -amine5-chloro-N-[(3-chloro-4-fluorophenyl)-(3,4,6,7-tetrahydropyrano[3,4-d]imidazol-2- yl)methyl]-6-methylpyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6- (difluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-6- methyl-5-(trifluoromethyl)pyridin-2-amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-2-(trifluoromethyl)thieno[3,2-b]pyridin-5-amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(1,1 -difluoroethyl)py ridin-3 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-2-(1,1 -difluoroethyl)py ridin-3 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(pentafluoro-Z6-sulfanyl)anilineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(pentafluoro-Z6-sulfanyl)aniline5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- yl)methyl]-4-fluoropyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-6-(pentafluoro-Z6-sulfanyl)pyridin-3-amine5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- yl)methyl]-4-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-2- methyl-6-(trifluoromethyl)pyridin-3-amine4-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- yl)methyl]-6-fluoropyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-6- methyl-4-(trifluoromethyl)pyridin-2-amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5-(1,1 -difluoroethyl)py ridin-3 -amine5-bromo-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- y l)methy 1] -3 -fluoropyridin-2 -amine4-chloro-N-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2- yl)methyl]-5-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3- fluoro-4-(trifluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3- (difluoromethyl)pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-3- methyl-5-(trifluoromethyl)pyridin-2-amineN-[(3-chloro-4-fluorophenyl)-(4-methyl-5-methylsulfonyl-lH-imidazol-2-yl)methyl]-4- fluoro-3 -methylanilineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4- (difluoromethyl)pyridin-2 -amine -350 2-( 1 -(3 -chloro-4-fluorophenyl)-2-(4-fluorophenyl)ethyl)-4-(methylsulfonyl)- IH-imida- zole -354 (2-((3-chloro-4-fluorophenyl)(4-fluorophenoxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -358 (2-((3-chloro-4-fluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone-362 (2-((3-chloro-4-fluorophenyl)((3,3-difluorocyclobutyl)methoxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -366 (2-((3-chloro-4-fluorophenyl)((4-fluorobenzyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -370 (2-((3-chloro-4-fluorophenyl)((4,4-difluorocyclohexyl)oxy)methyl)-5-methyl-lH-imida- zol-4 -y 1) (imino) (methyl) -16 -sulfanone -374 (2-((3-chlorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -378 imino(methyl)(5-methyl-2-((((trans)-4-(trifluoromethyl)cyclohexyl)oxy)(3-(trifluorome- thyl)phenyl)methyl)-lH-imidazol-4-yl)-16-sulfanone -382 imino(methyl)(5-methyl-2-((((trans)-4-(trifluoromethyl)cyclohexyl)oxy)(4-(trifluorome- thyl)phenyl)methyl)-lH-imidazol-4-yl)-16-sulfanone -386 (2-((3-(difluoromethyl)phenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -390 (2-((3,5-difluorophenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -394 (2-((4-(difluoromethyl)phenyl)(((trans)-4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -398 (2-((3-chloro-4-fluorophenyl)((3-(trifluoromethyl)bicyclo[l.l.l]pentan-l-yl)me- thoxy)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((2-chlorobenzyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((2-methoxybenzyl)oxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((2-(difluoromethyl)benzyl)oxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((7,7-difluorospiro[2.5]octan-4-yl)oxy)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -406 (2-((4-chloro-3-fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4 -y 1) (imino) (methyl) -16 -sulfanone -410 (2-((3-chloro-2,4-difluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -414 (2-((4-chloro-3-fluorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -418 (2-(((3,5-difluoropyridin-2-yl)amino)(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -422 (2-(((5-chloropyridin-2-yl)amino)(3,4-dichloro-2-fluorophenyl)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -426 (2-((3,4-dichlorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4 -yl) (imino) (methyl) -16 -sulfanone -430 (2-((3,4-dichloro-2-fluorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -434 (2-((3-chloro-4-fluorophenyl)((3,5-difluoropyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -438 (2-((4-chloro-3-fhiorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -442 (2-((3-chloro-2,4-difhiorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -446 (2-((3,4-dichloro-2-flnorophenyl)((3-fhioro-5-(trifluoromethyl)pyridin-2-yl)amino)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone-450 (2-((3-chloro-4-fluorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -454 (2-((3,4-dichlorophenyl)((3-fluoro-5-(trifluoromethyl)pyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -458 (2-((3-chloro-4-fluorophenyl)((5-chloropyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zol-4 -y 1) (imino) (methyl) -16 -sulfanone -462 (2-(((5-chloropyridin-2-yl)amino)(3-fluoro-4-(trifluoromethoxy)phenyl)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -466 (2-(((5-chloropyridin-2-yl)amino)(3,4-dichlorophenyl)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -470 (2-((3-chloro-4-fluorophenyl)((5-chloro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -474 (2-((3-chloro-4-fluorophenyl)((4-(trifluoromethyl)thiazol-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -478 (2-((3-chloro-4-fluorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -482 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -486 5-chloro-N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imida- zol-2-yl]methyl]-6-(difluoromethyl)pyridin-2 -amine -490 (2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -494 (2-((3-chloro-4-fluorophenyl)((5-chloro-4-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -498 (2-((3-chloro-4-fluorophenyl)((5-chloro-6-cyclopropylpyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -502 (2-((3-chloro-4-fluorophenyl)((3,5-difluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -505 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-(methyl-d3)pyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -509 N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl] -5-methyl-4-(trifluoromethyl)- 1 ,3 -thiazol-2 -amine -513 (2-((3-chloro-4-fluorophenyl)((6-(l,l-difluoroethyl)-5-fluoropyridin-2-yl)amino)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -517 (2-((3-chloro-4-fluorophenyl)((6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -521 (2-(((5-fluoro-6-methylpyridin-2-yl)amino)(4-(trifluoromethyl)phenyl)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -525 (2-((3,4-dichlorophenyl)((5-fluoro-4-methylpyrimidin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -529 6-(((3,4-dichlorophenyl)(5-methyl-4-(S-methylsulfonimidoyl)-lH-imidazol-2-yl)me- thyl)amino)-2-methylnicotinonitrile -533 (2-((3,4-dichlorophenyl)((5-fluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone -537 (2-((3-chlorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -541 6-(((3-chloro-4-fluorophenyl)(5-methyl-4-(S-methylsulfonimidoyl)-lH-imidazol-2- yl)methyl)amino)-2-methylnicotinonitrile -545 (2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone-549 (2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -553 (2-((3-chloro-4-fluorophenyl)((6-ethyl-5-fluoropyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -557 (2-((3-chloro-4-fluorophenyl)((6-cyclopropyl-5-fluoropyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -561 (2-((3-(difluoromethyl)phenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -565 (2-(((5-fluoro-6-methylpyridin-2-yl)amino)(3-(trifluoromethoxy)phenyl)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -569 (2-((3-(difluoromethoxy)phenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -573 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(me- thoxymethyl)-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -577 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(hydro- xymethyl)-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -581 (2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -585 (2-((3,5-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone -589 (2-((3-chloro-2,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -593 (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-lH-imida- zol-4 -y 1) (imino) (methyl) -16 -sulfanone -597 (2-((3-chloro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -601 (2-((5-chloro-4-fluoro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -605 (2-((5-chloro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -609 (2-((3,4-difluoro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -613 (2-((3-chloro-4-fluorophenyl)((l-methyl-3-(trifluoromethyl)-lH-pyrazol-5- yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -617 (2-((4-chloro-3-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -621 (2-((3-chloro-2-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -625 (2-((5-chloro-2-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -629 (2-((3-chloro-5-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -633 (2-((4-(difluoromethyl)phenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone -637 N-((3-chloro-4-fluorophenyl)(5-methyl-4-(methylsulfinyl)-lH-imidazol-2-yl)methyl)-5- fhioro-6-methylpyridin-2-amine (2-((3-chloro-4-fluorophenyl)((4-methyl-5-(trifluoromethyl)thiazol-2-yl)amino)methyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone (2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methoxypyridin-2-yl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone2-fluoro-5-(((5-fluoro-6-methylpyridin-2-yl)amino)(5-methyl-4-(S-methylsulfo- nimidoyl)-lH-imidazol-2-yl)methyl)benzonitrileN-[[4-(difluoromethyl)phenyl]-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2- y 1] methyl] -3 ,5 -difluoropy ridin-2 -amine (2-((3,4-dichloro-2-fluorophenyl)((3,5-difluoro-6-methylpyridin-2-yl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluorophenyl)((4-methoxy-5-methylpyrimidin-2-yl)amino)methyl)-4- methyl- 1 H-imidazol-5-yl)(imino)(methyl)-Z6-sulfanone(2-((3-chloro-4-fluorophenyl)((2,3 -dihydro-[ 1 ,4]dioxino [2,3 -b]pyridin-6-yl)amino)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluoro-2-methoxyphenyl)((5-fluoro-6-methylpyridin-2-yl)amino)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone6-(((3-chloro-4-fluorophenyl)(5-methyl-4-(S-methylsulfonimidoyl)-lH-imidazol-2- yl)methyl)amino)-3-fluoropicolinonitrile(2-(((5-chloro- 1 -methyl- lH-pyrazol-3 -yl)amino)(3 -chloro-4-fluorophenyl)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluorophenyl)((5-(4-fluorophenyl)thiazol-2-yl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone2-((3-chloro-4-fluorophenyl)((6,6-difluorobicyclo[3.1.0]hexan-3-yl)oxy)methyl)-5-me- thyl-4-(methylsulfonyl)-lH-imidazole -651 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl- lH-imidazole-4-sulfonamide -653 2-((3-chloro-4-fluorophenyl)((5-fluoropyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zole-4-sulfonamide -655 2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH- imidazole-4-sulfonamide -657 2-((3-chloro-4-fluorophenyl)((5-fluoro-4-methylpyrimidin-2-yl)amino)methyl)-5-me- thyl- lH-imidazole-4-sulfonamide -659 2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-N,5-dimethyl- lH-imidazole-4-sulfonamide -661 2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-lH-imidazole-4- sulfonamide -663 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-lH-imida- zole-4-sulfonamide -665 2-((3-chloro-4-fluorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)me- thyl)- lH-imidazole-4-sulfonamide 2-((3-chlorophenyl)((6-(difluoromethyl)-5-fluoropy ridin-2 -yl)amino)methyl)-lH-imida- zole-4-sulfonamide2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(hydro- xymethyl)-lH-imidazole-4-sulfonamide -669 2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-(me- thoxymethyl)-lH-imidazole-4-sulfonamide -671 2-((3-c hlorophenyl)((5-fluoro-6-methylpy ridin-2 -yl)amino)methyl)-lH-imidazole-4-sul- fonamide -673 2-((3 -chloro-4-fluorophenyl)((3 ,3 -difluorocyclobutyl)methoxy)methyl)-5-methyl- 1H- imidazole-4-sulfonamide2-((3-chlorophenyl)((4,4-difluorocyclohexyl)oxy)methyl)-lH-imidazole-4-sulfonamideN-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonylmethyl)-lH-imidazol-2- y 1] methyl] -5 -fluoro-6-methy Ipy ridin-2 -amine5-chloro-N-[(4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]pyridin-2 -amine(2-(((4,4-difluorocyclohexyl)oxy)(4-fluorophenyl)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone(2-((4-fluorophenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imida- zol-4 -y 1) (imino) (methyl) -16 -sulfanoneN-[(3,5-difluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-3.5-difluoropyridin-2-amine(2-((3-fluorophenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imida- zol-4 -y 1) (imino) (methyl) -16 -sulfanone3.5-difluoro-N-[(3-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]pyridin-2 -amine imino(2-((3-methoxyphenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-4-methyl-lH- imidazol-5-yl)(methyl)-16-sulfanone3.5-difluoro-N-[(3-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]pyridin-2 -amineN-[[3-(difluoromethyl)phenyl]-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2- y 1] methyl] -3 ,5 -difluoropy ridin-2 -amine3.5-difluoro-N-[[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]-[4-(trifluorome- thyl)phenyl]methyl]py ridin-2 -amine3.5-difluoro-N-[[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]-[3-(trifluorome- thyl)phenyl]methyl]py ridin-2 -amine(2-((2-fluorophenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH-imida- zol-4 -yl) (imino) (methyl) -16 -sulfanone(2-((2-(difluoromethyl)phenyl)((4-(trifluoromethyl)cyclohexyl)oxy)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone5-fluoro-6-methyl-N-[[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]-phenylme- thyl]pyridin-2 -amine5-fluoro-N-[(4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl] -6-methylpyridin-2 -amine5-fluoro-N-[(3-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl] -6-methylpyridin-2 -amine5-fluoro-N-[(3-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-6-methylpyridin-2 -amine5-fluoro-N-[(4-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-6-methylpyridin-2 -amine5-fluoro-N-[(2 -metho xyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-6-methylpyridin-2 -amine5-chloro-N-[(5-chlorothiophen-2-yl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2 -y 1] methyl] py ridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3-(difluoromethoxy )pyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-5- cyclopropyl-3 -fluoropyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-3- fhioro-5-(trifluoromethyl)pyridin-2 -amine2-[(3-chloro-4-fluorophenyl)-[(7,7-difluoro-3-bicyclo[4.1.0]heptanyl)oxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-(l-cyclohexylethoxy)methyl]-4-methyl-5-methylsulfonyl- IH-imidazole2-((3-chloro-4-fluorophenyl)((2-fluorocyclohexyl)oxy)methyl)-5-methyl-4-(methylsul- fonyl)- IH-imidazole2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5- methyl- lH-imidazole-4-sulfonamide2-[(3-chloro-4-fluorophenyl)-(2-methylcyclohexyl)oxymethyl]-4-methyl-5-methylsul- fonyl- IH-imidazole(2-((4,4-difluorocyclohexyl)(4-fluoro-3-methylphenoxy)methyl)-4-methyl-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluorophenyl)(cyclohexyloxy)methyl)-5-methyl-lH-imidazol-4- yl)(imino)(methyl)-16-sulfanone2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-methyl- lH-imidazole-4-sulfonamide2-[(3-chloro-4-fluorophenyl)-(2,2-difluorospiro[2.5]octan-6-yl)oxymethyl]-5-methyl-4- methylsulfonyl-lH-imidazole2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-me- thyl- lH-imidazole-4-sulfonamide2-[(3-chloro-4-fluorophenyl)-[(4,4-difluoro-l-methylcyclohexyl)methoxy]methyl]-5- methyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(3-fluorophenyl)methoxy]methyl]-5-methyl-4-methylsul- fonyl- IH-imidazole(2-((3,4-difluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-me- thyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone2-[(3-chloro-4-fluorophenyl)-(2 -metho xy cyclo hexyl)oxy methyl] -4-methy 1-5 -methylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(5-fluoro-2,3-dihydro-lH-inden-2-yl)oxy]methyl]-5-me- thyl-4-methylsulfonyl-lH-imidazole2-[(3-chloro-4-fluorophenyl)-[(4-propan-2-ylphenyl)methoxy]methyl]-4-methyl-5-me- thylsulfonyl- IH-imidazole2-[(3-chloro-4-fluorophenyl)-[(2-methylpyrazol-3-yl)methoxy]methyl]-5-methyl-4-me- thylsulfonyl- IH-imidazoleN-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thy 1] -5 -(trifluoromethoxy )py ridin-2 -amineN-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thy 1] -5 -(difluo ro metho xy)py ridin-2-amine5-chloro-N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imida- zol-2-yl]methyl]-6-(trideuteriomethyl)pyridin-2 -amine5-chloro-N-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imida- zol-2-yl]methyl]-4-methylpyridin-2 -amineN-[(3,4-dichlorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]methyl]-3,5-difluoro-6-methylpyridin-2-amineN-[(3-chloro-2,4-difluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-3,5-difluoro-6-methylpyridin-2 -amine5-chloro-N-((3-chloro-4-fluorophenyl)(4-methyl-5-(methylsulfonyl)-lH-imidazol-2- yl)methyl)-4-methylpyrimidin-2 -amineN-[(3-chloro-4-fluorophenyl)-(5-methyl-4-methylsulfonyl-lH-imidazol-2-yl)methyl]-4-(difluoromethyl)-5-fluoropyridin-2-amineN-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl] -4-(l , 1 -difluoroethyl)- 1 ,3 -thiazol-2 -amine5-chloro-N-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imida- zol-2-yl]methyl] - 1 ,3 -thiazol-2 -amine(2-((3-chloro-4-fluorophenyl)((4-(difluoromethyl)cyclohexyl)oxy)methyl)-5-methyl-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone2-[(3-chloro-4-fluorophenyl)-(l-cyclopropylethoxy)methyl]-4-methyl-5-methylsulfonyl- IH-imidazole5-chloro-N-[(3,4-dichlorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- yl]methyl]-4-methylpyrimidin-2 -amine(2-((3-chloro-4-fluorophenyl)((4,4-difluoro-2-methylcyclohexyl)oxy)methyl)-4-methyl- lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5- methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanoneN-[(5-chloro-4-fluoro-2 -metho xyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imida- zol-2-yl]methyl]-5-fluoro-6-methylpyridin-2 -amineN-[(4-chloro-2-methoxyphenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- y 1] methyl] -5 -fluoro-6-methy Ipy ridin-2 -amineN-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]-5-fluoro-4,6-dimethylpyrimidin-2 -amineN-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]-5-fluoro-4-methoxy-6-methylpyridin-2 -amine3-chloro-N-[(3,4-difluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2- y 1] methyl] -5 -fluoro-6-methy Ipy ridin-2 -amine(2-((3,4-difluorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone(2-(((5-cyclopropoxy-6-methylpyridin-2-yl)amino)(3,4-difluorophenyl)methyl)-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone(2-(((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)(3,4-difluorophenyl)methyl)-4-(methoxymethyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-4-(methoxymethyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone(2-((3-chlorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)-lH- imidazol-4-yl)(imino)(methyl)-16-sulfanone(2-((3,4-dichlorophenyl)((4,4-difluorocyclohexyl)amino)methyl)-5-methyl-lH-imidazol-4 -y 1) (imino) (methyl) -16 -sulf ano ne(2-(((5-fluoro-6-methylpyridin-2-yl)amino)(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)me- thyl)-5-methyl-lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone(2-((3-chlorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-4-(me- thoxymethyl)-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluorophenyl)((5,7-dihydrofuro[3,4-b]pyridin-2-yl)amino)methyl)-4-me- thyl-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanone(2-((3-chloro-4-fluorophenyl)((5,7-dihydrofuro[3,4-d]pyrimidin-2-yl)amino)methyl)-4- methyl-lH-imidazol-5-yl)(imino)(methyl)-16-sulfanoneN-[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]-5,6-difluoropyridin-2 -amine(2-(((4,4-difluorocyclohexyl)oxy)(3,4-difluorophenyl)methyl)-4-methyl-lH-imidazol-5- yl)(imino)(methyl)-16-sulfanone[6-[[(3-chloro-4-fluorophenyl)-[5-methyl-4-(methylsulfonimidoyl)-lH-imidazol-2- y 1] methyl] amino] -3 -fluo ropy ridin-2 -y 1] methanolN-[(3-chloro-4-fluorophenyl)-[5-[(dimethylamino)methyl]-4-(methylsulfonimidoyl)-lH- imidazol-2-yl]methyl]-5-fluoro-6-methylpyridin-2 -amineN-[(3-chloro-4-fluorophenyl)-[4-methyl-5-(methylsulfonimidoyl)-lH-imidazol-2-yl]me- thyl]-5-fluoro-4-methoxy-6-methylpyrimidin-2 -amine2-[(3-chlorophenyl)-[(5-fluoro-6-methylpyridin-2-yl)amino]methyl]-N-methyl-lH- imidazole-4-sulfonamideIll 2-[(3,4-difluorophenyl)-[(5-fluoro-6-methylpyridin-2-yl)amino]methyl]-5-(methoxyme- thyl)- lH-imidazole-4-sulfonamide778 2-[(3-chlorophenyl)-[[5-(difluoromethoxy)-6-methylpyridin-2-yl]amino]methyl]-lH- imidazole-4-sulfonamide779 2-[(3,4-dichlorophenyl)-[(5-fluoro-4-methylpyrimidin-2-yl)amino]methyl]-4-methyl- lH-imidazole-5-sulfonamide780 2-[(3 ,4-dichlorophenyl)-( 1 , 1 -dioxo thietan-3-yl)oxy methyl] -5-methyl- lH-imidazole-4- sulfonamide782 (2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)(methyl)amino)methyl)-5-methyl- lH-imidazol-4-yl)(imino)(methyl)-16-sulfanone783 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclobutyl)methoxy]methyl]-5-(methoxyme- thyl)- lH-imidazole-4-sulfonamide784 2-[(3-chloro-4-fluorophenyl)-[(3,3-difluorocyclobutyl)methoxy]methyl]-4-(hydroxyme- thyl)-lH-imidazole-5-sulfonamide785 2-((3,4-difhiorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)-lH- imidazole-4-sulfonamide786 2-(((5-cyclopropoxy-6-methylpyridin-2-yl)amino)(3 ,4-difluorophenyl)methyl)- 1H- imidazole-4-sulfonamide787 2-((3-chlorophenyl)((6-methyl-5-(trifluoromethoxy)pyridin-2-yl)amino)methyl)-lH- imidazole-4-sulfonamide788 2-((3-chlorophenyl)((5-(difluoromethoxy)-6-methylpyridin-2-yl)amino)methyl)-lH- imidazole-4-sulfonamide789 2-((3-chlorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-5-(me- thoxymethyl)-lH-imidazole-4-sulfonamide790 2-((3-chloro-4-fluorophenyl)(3-(trifluoromethyl)cyclobutoxy)methyl)-5-methyl-lH- imidazole-4-sulfonamide791 2-((3-chlorophenyl)((5-fluoro-6-methylpyridin-2-yl)amino)methyl)-5-methyl-lH-imida- zole-4-sulfonamide792 2-((3,4-dichlorophenyl)((5-fluoro-4-methylpyrimidin-2-yl)amino)methyl)-5-methyl-lH- imidazole-4-sulfonamide793 2-((3 -chlorophenyl)((5-fluoropyridin-2-yl)amino)methyl)-5-( 1 , 1 -difluoroethyl)- 1H- imidazole-4-sulfonamide794 2-((4-chlorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)-lH-imida- zole-4-sulfonamide795 2-((3-chloro-4-fluorophenyl)((6-(difluoromethyl)-5-fluoropyridin-2-yl)amino)methyl)- lH-imidazole-4-sulfonamide in the form of the free compound or a physiologically acceptable salt thereof.

14. A pharmaceutical dosage form comprising a compound according to any of claims 1 to 13.

15. The compound according to any of claims 1 to 13 for use in the treatment of pain.

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