Heteroarylphenyl ether derivatives

Abstract

The present invention provides novel compounds having the general formula (I) wherein R1 to R2, L1 to L5, A1 to A4 are as described herein, or a pharmaceutically acceptable salt thereof, compositions including the compounds and methods of using the compounds.

Description

[0001] Case: 39063 Heteroarylphenyl ether derivatives FIELD OF THE INVENTION The present invention relates to organic compounds, in particular to CDK8 / 19 inhibitors, useful for treatment of cancers in a mammal. In particular, the present invention relates to CDK8 / 19 inhibitors that have CDK8 / 19 inhibition activity, as well as their manufacture, pharmaceutical compositions containing them and their potential use as medicaments. BACKGROUND OF THE INVENTION Cyclin-dependent kinase 8 (CDK8) and its paralog CDK19, in association with cyclin C, are integral parts of the mediator complex that play vital roles in regulating transcription by phosphorylating RNPII and other specific transcription factors (Dannappel et al. Front. Cell Dev. Biol.2019.). Unlike most CDKs, CDK8 / 19 only regulates transcription but not cell cycle or cell proliferation, and in contrast to some other transcriptional CDKs, they only regulate a subset of genes related to cell activation, have minimal impact on basal gene expression (Fant et al. Transcription.2019). The CDK8−cyclin C complex directly or indirectly regulates a variety of signaling pathways, including STAT1 (Bancerek et al Immunity.2013), Wnt-βcatenin (Firestein et al. Nature, 2008), Notch, Smads, HIF1α, p21 / p53, and NFκB (Li et al. Cells.2019). This suggests that cellular context will have a major impact on the transcriptional response to CDK8 inhibition. In addition to widely studied role of CDK8 in numerous cancer, CDK8 / 19 has also been implicated in the development of several other diseases including inflammation (Chen et al. PNAS.2017), viral diseases (Birkenheuer et al. J. Virol.2015), autoimmune (Guo et al. Front Immunol.2019), cardiovascular diseases (Hall et al. JCI Insight.2017) and osteoporosis (Yamada et al. Stem Cell Reports.2022). In particular, recent studies have shown that CDK8 / 19 phosphorylate STAT5 leads to retention of STAT5 in the cytosol, suppression of STAT-5- dependent Foxp3 expression, and eventually decreased formation of Foxp3+ Treg cells. In addition, CDK8 / 19 negatively regulates the expression of the anti-inflammatory cytokine IL-10 by phosphorylation of the c-Jun part of the AP-1 transcription factor. Consistently, pharmacological or genetic inhibition of CDK8 / 19 leads to increased expression of Foxp3+ (Akamatsu et al. Sci Immunol.2019) and IL-10 (Johannessen et al. Nat Chem Biol.2017) in activated T cells and myeloid cells, respectively. These work further supports a general role for CDK8 / 19 in control of inflammation and tolerance in both the innate and adaptive immune compartments. Moreover, clinical studies indicate therapeutic benefits of adaptive Treg transfer or treatment of recombinant IL-10 in a wide range of immune-mediated diseases including autoimmune diseases (Duffy et al. Front. Neurosci.2019), organ transplantation rejection (Juneja et al. Front Immunol.2022), multiple sclerosis, GvHD (Guo et al. Front. Immunol. 2021) as well as some other diseases such as cardiovascular diseases (Albany et al. Front Immunol.2019). Given the widely proven anti-inflammatory effects of Treg and IL-10 in preclinical and clinical studies, a small molecule CDK8 / 19 inhibitor can manipulating Treg cells and IL-10 becomes a promising therapeutic strategy for treating various immune mediated diseases. SUMMARY OF THE INVENTION Objects of the present invention are novel compounds of formula (I), their manufacture, medicaments based on a compound in accordance with the invention and their production as well as the use of compounds of formula (I) as CDK8 / 19 inhibitors for the treatment of a broad spectrum of immune mediated diseases. The compounds of formula (I) show superior CDK8 / 19 inhibition activity. The compounds of formula (I) can also increase expression of Foxp3+ and IL-10 in activated T cells and myeloid cells. In addition, the compounds of formula (I) also show good selectivity as well as good safety and PK profiles, e.g., good solubility, microsome stability, permeability, and safety margin. One aspect of the invention pertains to a compound of formula (I), wherein R1is an 8 to 10 membered bicyclic heteroaryl containing one to three heteroatoms independently selected from N, O, and S, or phenyl, wherein R1is substituted with R1a, R1b, and R1c, when R1is heteroaryl, each of R1a, R1b, and R1cis independently selected from H, halogen, C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, haloC1-6alkyl, acyl, carbamoyl, cyano, oxo, azetidinecarbonyl, and a 5 to 8 membered monocyclic heteroaryl or heterocyclyl containing one, two, three, or four heteroatoms independently selected from N, O, and S, wherein said heteroaryl and heterocyclyl can be optionally substituted by one, two, or three Q, each Q is independently selected from halogen, C1-6alkyl, deuterated C1-6alkyl, hydroxyC1-6alkyl, haloC1-6alkyl, C3-10cycloalkyl, C1-6alkoxyC1-6alkyl, carbamoyl, and oxo, and at least one of R1a, R1b, and R1cis not H, or when R1is phenyl, each of R1a, R1b, and R1cis independently selected from H, C1-6alkyl, carbamoyl, cyano, and a 5 to 8 membered monocyclic heteroaryl containing one, two, three, or four heteroatoms independently selected from N, O, and S, wherein said heteroaryl can be optionally substituted by C1-6alkyl, and at least one of R1a, R1b, and R1cis not H; L1 is O, NH or CH2; A1 is CR3or N; A2 is CR4or N; A3 is CR5or N; A4 is CR6or N; wherein no more than two of A1 to A2 are N; each of R3to R6is independently selected from H, halogen and C1-6alkyl; absent; L3 is O or absent; L4 is C3-10cycloalkylene or (CH2)n, substituted with one, two, or three R7, n is 0, 1, 2, or 3, each R7is independently selected from H, halogen, and C1-6alkyl; L5 is absent or selected from O, carbonyl, NH, (CO)NH, and NH(CO); R2is selected from H, hydroxyl, C1-6alkyl, hydroxyC1-6alkyl, haloC1-6alkyl, haloC3-10cycloalkyl, (C1-6alkyl)2amino, C1-6alkylsulfonyl, C3-10cycloalkyl, 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, 5 to 10 membered heteroaryl containing one to three heteroatoms selected from N, O, and S, and benzyl, wherein each of the heterocyclyl and heteroaryl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, halogen, C1-6alkyl, haloC1-6alkyl, C1-6alkoxyC1-6alkyl, C3-10cycloalkyC1-6alkyl, oxetan-3-ylC1-6alkyl, C3-10cycloalkyl, C1-6alkylC3-10cycloalky, C1-6alkylC1-6alkoxy, acyl, hydroxylacyl, C1-6alkoxyacyl, hydroxyl, hydroxyC1-6alkyl, C3-10cycloalkylcarbonyl, and oxo, or a pharmaceutically acceptable salt thereof. Another aspect of the invention pertains to a process for the preparation of a compound of formula (I), as well as a compound of formula (I) or a pharmaceutically acceptable salt thereof when manufactured according to the process. Another aspect of the invention pertains to a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Another aspect of the invention pertains to a compound of formula (I) or a pharmaceutically acceptable salt thereof for use as therapeutically active substance. Another aspect of the invention pertains to a compound of formula (I) or a pharmaceutically acceptable salt thereof for use in the treatment of immune mediated diseases. Another aspect of the invention pertains to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the treatment of immune mediated diseases. Another aspect of the invention pertains to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the inhibition of CDK8 and / or CDK19. Another aspect of the invention pertains to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment of immune mediated diseases. Another aspect of the invention pertains to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the inhibition of CDK8 and / or CDK19. Another aspect of the invention pertains to a method for the treatment of immune mediated diseases, which method comprises administering an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. DETAILED DESCRIPTION OF THE INVENTION DEFINITIONS Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Furthermore, the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention. The nomenclature used in this application is based on IUPAC systematic nomenclature, unless indicated otherwise. The term “compound(s) of this invention” and “compound(s) of the present invention” refers to compounds of formula (I), formula (Ia), formula (Ib), formula (Ic), or formula (Id), and stereoisomers, solvates or salts thereof (e.g., pharmaceutically acceptable salts). The term “substituent” denotes an atom or a group of atoms replacing a hydrogen atom on the parent molecule. The term “C1-6alkyl” alone or in combination signifies a saturated, linear- or branched chain alkyl group containing 1 to 6, particularly 2 to 6 or 1 to 4 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl and the like. Particular “C1-6alkyl” groups are methyl and ethyl. The term “C1-6alkylene” denotes a linear saturated divalent hydrocarbon group of 1 to 6 carbon atoms or a divalent branched saturated divalent hydrocarbon group of 3 to 6 carbon atoms. Examples of alkylene groups include methylene, ethylene, propylene, 2-methylpropylene, butylene, 2-ethylbutylene, pentylene, hexylene. The term “halogen” or “Halo” denotes fluoro, chloro, bromo, or iodo. The term “haloC1-6alkyl” denotes an alkyl group wherein at least one of the hydrogen atoms of the alkyl group is replaced by same or different halogen atoms, particularly fluoro atoms. Examples of haloC1-6alkyl include monochloro-, difluoro-or trifluoro-methyl, -ethyl or -propyl, for example difluoromethyl. The term “C3-10cycloalkyl” denotes a monovalent saturated monocyclic or bicyclic hydrocarbon group of 3 to 10 ring carbon atoms. In particular embodiments cycloalkyl denotes a monovalent saturated monocyclic hydrocarbon group of 3 to 8 ring carbon atoms. Bicyclic means consisting of two saturated carbocycles having one or more carbon atoms in common. Particular cycloalkyl groups are monocyclic. Examples for monocyclic cycloalkyl are cyclopropyl, cyclobutanyl, cyclopentyl, cyclohexyl or cycloheptyl. Examples for bicyclic cycloalkyl are bicyclo[2.2.1]heptanyl, or bicyclo[2.2.2]octanyl. The term “C3-10cycloalkylene” denotes a saturated divalent monocyclic or bicyclic hydrocarbon group of 3 to 10 ring carbon atoms. The term “heteroaryl” denotes a monovalent aromatic heterocyclic mono- or bicyclic ring system of 5 to 12 ring atoms, comprising 1, 2, 3 or 4 heteroatoms selected from N, O and S, the remaining ring atoms being carbon. Examples of heteroaryl moieties include, but not limited to, pyrrolyl, furanyl, thienyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridinyl, pyrazinyl, pyrazolyl, pyridazinyl, pyrimidinyl, triazinyl, isoxazolyl, benzofuranyl, isothiazolyl, benzothienyl, indolyl, isoindolyl, isobenzofuranyl, benzimidazolyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, benzooxadiazolyl, benzothiadiazolyl, benzotriazolyl, purinyl, quinolinyl, isoquinolinyl, quinazolinyl or quinoxalinyl. Heteroaryl can be further substituted by halogen, C1-6alkyl, haloC1-6alkyl, cyano, C3-7cycloalkyl, (C1-6alkyl)2amino, or C1-6alkoxy. The term “heterocyclyl” denotes a monovalent saturated or partly unsaturated mono- or bicyclic ring system of 3 to 9 ring atoms, comprising 1, 2, or 3 ring heteroatoms selected from N, O and S, the remaining ring atoms being carbon. In particular embodiments, heterocyclyl is a monovalent saturated monocyclic ring system of 4 to 7 ring atoms, comprising 1, 2, or 3 ring heteroatoms selected from N, O and S, the remaining ring atoms being carbon. Examples for monocyclic saturated heterocyclyl are aziridinyl, oxiranyl, azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydro-thienyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxo-thiomorpholin-4-yl, azepanyl, diazepanyl, homopiperazinyl, oxazepanyl, oxopiperidinyl, oxopiperazinyl or oxopyrrolidinyl. Examples for bicyclic saturated heterocyclyl are azaspiro[3.3]heptanyl, 8-aza-bicyclo[3.2.1]octyl, quinuclidinyl, 8-oxa-3-aza- bicyclo[3.2.1]octyl, 9-aza-bicyclo[3.3.1]nonyl, 3-oxa-9-aza-bicyclo[3.3.1]nonyl, or 3-thia-9-aza- bicyclo[3.3.1]nonyl. Examples for partly unsaturated heterocyclyl are dihydrofuryl, imidazolinyl, dihydro-oxazolyl, tetrahydro-pyridinyl, or dihydropyranyl. The term “hydroxyC1-6alkyl” denotes a C1-6alkyl group wherein at least one of the hydrogen atoms of the C1-6alkyl group has been replaced by a hydroxy group. The compounds according to the present invention may exist in the form of their pharmaceutically acceptable salts. The term “pharmaceutically acceptable salt” refers to conventional acid-addition salts or base-addition salts that retain the biological effectiveness and properties of the compounds of formula (I) and are formed from suitable non-toxic organic or inorganic acids or organic or inorganic bases. Acid-addition salts include for example those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, phosphoric acid and nitric acid, and those derived from organic acids such as p-toluenesulfonic acid, trifluoroacetic acid, formic acid, salicylic acid, methanesulfonic acid, oxalic acid, succinic acid, citric acid, malic acid, lactic acid, fumaric acid, and the like. Base-addition salts include those derived from ammonium, potassium, sodium and, quaternary ammonium hydroxides, such as for example, tetramethyl ammonium hydroxide. The chemical modification of a pharmaceutical compound into a salt is a technique well known to pharmaceutical chemists in order to obtain improved physical and chemical stability, hygroscopicity, flowability and solubility of compounds. It is for example described in Bastin R.J., et al., Organic Process Research & Development 2000, 4, 427-435. Particular are the sodium salts of the compounds of formula (I). The term “therapeutically effective amount” denotes an amount of a compound or molecule of the present invention that, when administered to a subject, (i) treats or prevents the particular disease, condition or disorder, (ii) attenuates, ameliorates or eliminates one or more symptoms of the particular disease, condition, or disorder, or (iii) prevents or delays the onset of one or more symptoms of the particular disease, condition or disorder described herein. The therapeutically effective amount will vary depending on the compound, the disease state being treated, the severity of the disease treated, the age and relative health of the subject, the route and form of administration, the judgement of the attending medical or veterinary practitioner, and other factors. The term “pharmaceutical composition” denotes a mixture or solution comprising a therapeutically effective amount of an active pharmaceutical ingredient together with pharmaceutically acceptable excipients to be administered to a mammal, e.g., a human in need thereof. CDK8 / 19 inhibitors The present invention relates to (i) a compound of formula (I), wherein R1is an 8 to 10 membered bicyclic heteroaryl containing one to three heteroatoms independently selected from N, O, and S, or phenyl, wherein R1is substituted with R1a, R1b, and R1c, when R1is heteroaryl, each of R1a, R1b, and R1cis independently selected from H, halogen, C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, haloC1-6alkyl, acyl, carbamoyl, cyano, oxo, azetidinecarbonyl, and a 5 to 8 membered monocyclic heteroaryl or heterocyclyl containing one, two, three, or four heteroatoms independently selected from N, O, and S, wherein said heteroaryl and heterocyclyl can be optionally substituted by one, two, or three Q, each Q is independently selected from halogen, C1-6alkyl, deuterated C1-6alkyl, hydroxyC1-6alkyl, haloC1-6alkyl, C3-10cycloalkyl, C1-6alkoxyC1-6alkyl, carbamoyl, and oxo, and at least one of R1a, R1b, and R1cis not H, or when R1is phenyl, each of R1a, R1b, and R1cis independently selected from H, C1-6alkyl, carbamoyl, cyano, and a 5 to 8 membered monocyclic heteroaryl containing one, two, three, or four heteroatoms independently selected from N, O, and S, wherein said heteroaryl can be optionally substituted by C1-6alkyl, and at least one of R1a, R1b, and R1cis not H; L1 is O, NH or CH2; A1 is CR3or N; A2 is CR4or N; A3 is CR5or N; A4 is CR6or N; wherein no more than two of A1 to A2 are N; each of R3to R6is independently selected from H, halogen and C1-6alkyl; absent; L3 is O or absent; L4 is C3-10cycloalkylene or (CH2)n, substituted with one, two, or three R7, n is 0, 1, 2, or 3, each R7is independently selected from H, halogen, and C1-6alkyl; L5 is absent or selected from O, carbonyl, NH, (CO)NH, and NH(CO); R2is selected from H, hydroxyl, C1-6alkyl, hydroxyC1-6alkyl, haloC1-6alkyl, haloC3-10cycloalkyl, (C1-6alkyl)2amino, C1-6alkylsulfonyl, C3-10cycloalkyl, 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, 5 to 10 membered heteroaryl containing one to three heteroatoms selected from N, O, and S, and benzyl, wherein each of the heterocyclyl and heteroaryl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, halogen, C1-6alkyl, haloC1-6alkyl, C1-6alkoxyC1-6alkyl, C3-10cycloalkyC1-6alkyl, oxetan-3-ylC1-6alkyl, C3-10cycloalkyl, C1-6alkylC3-10cycloalky, C1-6alkylC1-6alkoxy, acyl, hydroxylacyl, C1-6alkoxyacyl, hydroxyl, hydroxyC1-6alkyl, C3-10cycloalkylcarbonyl, and oxo, or a pharmaceutically acceptable salt thereof. A further embodiment of present invention is (ii) the compound according to embodiment (i), wherein R1is an 8 to 10 membered bicyclic heteroaryl containing one to three heteroatoms independently selected from N, or phenyl, wherein R1is substituted with R1a, R1b, and R1c, when R1is heteroaryl, each of R1a, R1b, and R1cis independently selected from H, halogen, C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, haloC1-6alkyl, acyl, carbamoyl, cyano, oxo, azetidinecarbonyl, and a 5 to 8 membered monocyclic heteroaryl containing one, two, or three heteroatoms independently selected from N, O, and S, wherein said heteroaryl can be optionally substituted by one or two Q, each Q is independently selected from C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, C1-6alkoxyC1-6alkyl, and carbamoyl, and at least one of R1a, R1b, and R1cis not H, or when R1is phenyl, each of R1a, R1b, and R1cis independently selected from H, C1-6alkyl, carbamoyl, cyano, and a 5 to 8 membered monocyclic heteroaryl containing one, two, or three heteroatoms independently selected from N, O, and S, wherein said heteroaryl can be optionally substituted by C1-6alkyl, and at least one of R1a, R1b, and R1cis not H. A further embodiment of present invention is (iii) the compound according to embodiment (i) or embodiment (ii), wherein R1is selected from 1H-indazolyl, imidazo[1,5-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, and indolinyl, wherein R1is substituted with R1a, R1b, and R1c, R1ais on the six-member ring of R1and is selected from carbamoyl, acyl, cyano, triazolyl, oxadiazolyl, thiadiazolyl, imidazolyl, pyridazinyl, and azetidinecarbonyl, wherein R1acan be optionally substituted by one or two Q, each Q is independently selected from C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, C1-6alkoxyC1-6alkyl, and carbamoyl, R1band R1care on the five-member ring of R1and each of R1band R1cis independently selected from H, halogen, C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, haloC1-6alkyl, and oxo, or R1is phenyl substituted with R1a, R1b, and R1c, each of R1a, R1b, and R1cis independently selected from H, C1-6alkyl, carbamoyl, cyano, triazolyl, imidazolyl, and pyridazinyl, wherein the triazolyl can be optionally substituted by C1-6alkyl, and at least one of R1a, R1b, and R1cis not H. A further embodiment of present invention is (iv) the compound according to any one of embodiments (i) - (iii), wherein R1is selected from 1H-indazolyl and imidazo[1,5-a]pyridinyl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl and triazolyl which can be optionally substituted by C1-6alkyl or C3-10cycloalkyl, R1bis on the five-member ring of R1and is selected from H, C1-6alkyl and C3- 10cycloalkyl. A further embodiment of present invention is (v) the compound according to any one of embodiments (i) - (iv), wherein R1is selected from 1H-indazol-6-yl, 1H-indazol-7-yl, imidazo[1,5-a]pyridin-5-yl, and imidazo[1,5-a]pyridin-8-yl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl, 4-ethyl-1,2,4-triazol- 3-yl, and 4-cyclopropyl-1,2,4-triazol-3-yl, R1bis on the five-member ring of R1and is selected from H, methyl, and cyclopropyl. A further embodiment of present invention is (vi) the compound according to any one of embodiments (i) - (v), wherein L1 is O. A further embodiment of present invention is (vii) the compound according to any one of embodiments (i) - (vi), wherein A1 is CR3, R3is selected from H, halogen and C1-6alkyl; A2 is CR4, R4is selected from H and halogen; A3 is CR5, R5is H; and A4 is CR6, R6is selected from H and halogen. A further embodiment of present invention is (viii) the compound according to any one of embodiments (i) - (vii), wherein A1 is CR3, R3is selected from H and halogen; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H. A further embodiment of present invention is (ix) the compound according to any one of embodiments (i) - (viii), wherein A1 is CR3, R3is selected from H and fluoro; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H. A further embodiment of present invention is (x) the compound according to any one of embodiments (i) - (ix), wherein L2is absent. A further embodiment of present invention is (xi) the compound according to any one of embodiments (i) - (x), wherein L4 is cyclobutylene or (CH2)n, substituted with one or two R7, n is 0, 1, 2, or 3, each R7is independently selected from H, halogen, and C1-6alkyl; A further embodiment of present invention is (xii) the compound according to any one of embodiments (i) - (xi), wherein L4 is (CH2)n, n is 0, 2, or 3. A further embodiment of present invention is (xiii) the compound according to any one of embodiments (i) - (xii), wherein L5 is absent or selected from O and carbonyl. A further embodiment of present invention is (xiv) the compound according to any one of embodiments (i) - (xiii), wherein R2is selected from H, hydroxyl, C1-6alkyl, hydroxyC1-6alkyl, (C1-6alkyl)2amino, C1- 6alkylsulfonyl, C3-10cycloalkyl, 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, 5 to 10 membered heteroaryl containing one to three heteroatoms selected from N, O, and S, and benzyl, wherein each of the heterocyclyl and heteroaryl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-10cycloalkyC1-6alkyl, oxetan-3-ylC1-6alkyl, C3-10cycloalkyl, C1-6alkylC3-10cycloalky, acyl, hydroxylacyl, C1-6alkoxyacyl, hydroxyl, hydroxyC1-6alkyl, C3-10cycloalkylcarbonyl, and oxo. A further embodiment of present invention is (xv) the compound according to any one of embodiments (i) - (xiv), wherein R2is selected from H, hydroxyl, C1-6alkyl, hydroxyC1-6alkyl, (C1-6alkyl)2amino, C1-6alkylsulfonyl, C3-10cycloalkyl, 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, 5 to 10 membered heteroaryl containing one to three heteroatoms selected from N, O, and S, and benzyl, wherein the heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidyl, tetrahydrothiopyranyl, tetrahydropyranyl, imidazolidinyl, piperazinyl, oxazolidinyl, morpholino, isothiazolidinyl, 2-oxaspiro[3.3]heptanyl, 2-oxaspiro[3.5]nonanyl, 2-oxa-7- azaspiro[3.4]octanyl, (1R,5S)-8-azabicyclo[3.2.1]octanyl, 8-oxabicyclo[3.2.1]octanyl, 3- oxa-6-azabicyclo[3.1.1]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5- azabicyclo[2.2.1]heptanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 2H-pyridinyl, 2,3- dihydrobenzofuranyl, 6,7-dihydro-4H-pyrazolo[1,5-a]pyrazinyl, 6,8-dihydro-5H- imidazo[1,5-a]pyrazinyl, 1,2-dihydroimidazolyl, and 5-azaspiro[2.4]heptanyl, and heteroaryl is selected from triazolyl and pyridyl, wherein each of the heterocyclyl and heteroaryl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-10cycloalkyC1-6alkyl, oxetan-3-ylC1-6alkyl, C3-10cycloalkyl, C1-6alkylC3-10cycloalky, acyl, hydroxylacyl, C1-6alkoxyacyl, hydroxyl, hydroxyC1-6alkyl, C3-10cycloalkylcarbonyl, and oxo. A further embodiment of present invention is (xvi) the compound according to any one of embodiments (i) - (xv), wherein R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, wherein the heterocyclyl is selected from pyrrolidinyl, piperidyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperazinyl, oxazolidinyl, morpholino (1R,5S)-8-azabicyclo[3.2.1]octanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, and 6-oxa-3- azabicyclo[3.1.1]heptanyl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, acyl, C1-6alkoxyacyl, and oxo. A further embodiment of present invention is (xvii) the compound according to any one of embodiments (i) - (xvi), wherein R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, wherein the heterocyclyl is selected from pyrrolidin-1-yl, 4-piperidyl, tetrahydrofuran-3- yl, tetrahydropyran-4-yl, imidazolidin-1-yl, piperazin-1-yl, oxazolidin-3-yl, morpholino, (1R,5S)-8-azabicyclo[3.2.1]octan-3-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, and 6-oxa- 3-azabicyclo[3.1.1]heptan-3-yl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, methyl, ethyl, acetyl, 2-methoxyacetyl, and oxo. A further embodiment of present invention is (xviii) a compound according to embodiment (i) or (ii), wherein R1is selected from 1H-indazolyl and imidazo[1,5-a]pyridinyl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl and triazolyl which can be optionally substituted by C1-6alkyl or C3-10cycloalkyl, R1bis on the five-member ring of R1and is selected from H, C1-6alkyl and C3-10cycloalkyl. L1 is O; A1 is CR3, R3is selected from H and halogen; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H; L2 is absent; L3 is O or absent; L4 is (CH2)n, n is 0, 2, or 3; L5 is absent or selected from O and carbonyl; R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, wherein the heterocyclyl is selected from pyrrolidinyl, piperidyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperazinyl, oxazolidinyl, morpholino (1R,5S)-8-azabicyclo[3.2.1]octanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, and 6-oxa-3- azabicyclo[3.1.1]heptanyl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, acyl, C1-6alkoxyacyl, and oxo. A further embodiment of present invention is (xix) a compound according to embodiment (xviii), wherein R1is selected from 1H-indazol-6-yl, 1H-indazol-7-yl, imidazo[1,5-a]pyridin-5-yl, and imidazo[1,5-a]pyridin-8-yl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl, 4-ethyl-1,2,4-triazol- 3-yl, and 4-cyclopropyl-1,2,4-triazol-3-yl, R1bis on the five-member ring of R1and is selected from H, methyl, and cyclopropyl; L1 is O; A1 is CR3, R3is selected from H and fluoro; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H; L2 is absent; L3is O or absent; L4 is (CH2)n, n is 0, 2, or 3; L5 is absent or selected from O and carbonyl; R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, wherein the heterocyclyl is selected from pyrrolidin-1-yl, 4-piperidyl, tetrahydrofuran-3- yl, tetrahydropyran-4-yl, imidazolidin-1-yl, piperazin-1-yl, oxazolidin-3-yl, morpholino, (1R,5S)-8-azabicyclo[3.2.1]octan-3-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, and 6-oxa- 3-azabicyclo[3.1.1]heptan-3-yl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, methyl, ethyl, acetyl, 2-methoxyacetyl, and oxo. A further embodiment of present invention is (xx) a compound selected from: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-[(1-methyl-4-piperidyl)oxy]ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 5-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 7-[4-(cyclopropylmethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-7-[4-[2-(1,2,4-triazol-4-yl)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-(2-oxopyrrolidin-1-yl)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-(3-methyl-2-oxo-imidazolidin-1-yl)ethoxy]phenoxy]indazole-5- carboxamide; 7-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 7-[3-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 8-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6-carboxamide; 3-methyl-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 1-methyl-8-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6- carboxamide; 5-[4-[3-(3-methylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(3-ethylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 1-methyl-7-[4-[2-(2-oxooxazolidin-3-yl)ethoxy]phenoxy]indazole-5-carboxamide; 5-[4-[3-(3,3-dimethylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(6-oxo-2-oxa-7-azaspiro[3.4]octan-7-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine- 7-carboxamide; 7-[4-[3-(2-benzyloxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-[3-(2-hydroxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1H-indazole-5-carboxamide; 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carbonitrile; 1-[1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5-yl]ethanone; 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 3-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6- carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyrazolo[4,3-b]pyridine-5- carbonitrile; 1-methyl-6-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-(cyclopropoxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide; 6-[4-(3-methoxy-3-methyl-butoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[3-(2-methyl-5-oxo-pyrrolidin-1-yl)propoxy]phenoxy]indazole-5- carboxamide; 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[rac-(3R,4R)-3-methyltetrahydropyran-4-yl]oxyethoxy]phenoxy]indazole- 5-carboxamide; 1-methyl-6-[4-[2-[rac-(3S,4R)-3-methyltetrahydropyran-4-yl]oxyethoxy]phenoxy]indazole- 5-carboxamide; 1-methyl-6-[4-(2-methyl-3-tetrahydropyran-4-yloxy-propoxy)phenoxy]indazole-5- carboxamide; 6-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-(3-morpholino-3-oxo-propoxy)phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-[3-oxo-3-(3-oxopiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-3-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3S)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3R)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 6-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2,6-difluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[2-methyl-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxamide; 6-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-[2-(8-oxabicyclo[3.2.1]octan-3-yloxy)ethoxy]phenoxy]indazole-5- carboxamide; 1-methyl-6-[4-[2-(2-oxaspiro[3.3]heptan-6-yloxy)ethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-(1,1-dioxothian-4-yl)oxyethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[2-(2-oxaspiro[3.5]nonan-7-yloxy)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-(2-methyltetrahydropyran-4-yl)oxyethoxy]phenoxy]indazole-5- carboxamide; 1-methyl-6-[4-(3-tetrahydropyran-4-ylpropoxy)phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[3-(1,1-dioxo-1,2-thiazolidin-2-yl)propoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-[3-(2-oxo-1-pyridyl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropyl)phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl-1,2,4- triazol-3-yl)benzonitrile; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl-1,2,4- triazol-3-yl)benzamide; 7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-7-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(4-methyl-2-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5- carboxamide; 1-methyl-7-[4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5- carboxamide; 1-methyl-7-[4-[3-(3-oxopiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 7-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole; 5-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 7-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 5-[2-fluoro-4-[3-(3-methyl-2-oxo-imidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5- a]pyridine-7-carboxamide; 5-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-(4-methyl-1,2,4-triazol-3- yl)benzamide; 4-(4-ethyl-1,2,4-triazol-3-yl)-2-[2-fluoro-4-[3-(2-oxooxazolidin-3- yl)propoxy]phenoxy]benzamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-imidazol-1-yl-benzamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-pyridazin-3-yl-benzamide; 1-methyl-6-[4-[2-(tetrahydrofuran-3-ylamino)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[[6-[3-(2-oxopyrrolidin-1-yl)propylamino]-3-pyridyl]oxy]indazole-5- carboxamide; 6-[2-fluoro-4-(3-oxo-3-pyrrolidin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-(3-morpholino-3-oxo-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 6-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]-1- methyl-indazole-5-carboxamide; 6-[2-fluoro-4-(3-oxo-3-piperazin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide; 1-methyl-6-[4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide; 6-[4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[3-(cyclopentylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-7-[4-(3-morpholino-3-oxo-propoxy)phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide; 7-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-[(3-hydroxybicyclo[1.1.1]pentane-1-carbonyl)amino]ethoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 1-methyl-2-oxo-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indoline-5-carboxamide; 1-methyl-6-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-[(1-acetyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(2-morpholino-2-oxo-ethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-oxo-2-(tetrahydropyran-4-ylamino)ethoxy]phenoxy]indazole-5- carboxamide; 6-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5- a]pyridine; 7-(4-methyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine; 7-(4-cyclopropyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine; 7-[4-(2-methoxyethyl)-1,2,4-triazol-3-yl]-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine; 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]-1,3,4- oxadiazole; 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-7-(4H-1,2,4-triazol-3-yl)imidazo[1,5- a]pyridine; 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]-1,3,4- thiadiazole; 7-(4,5-dimethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine; 3-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propan-1-ol; 3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propan-1-ol; 4-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]-2-methyl- butan-2-ol; 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(3-methylsulfonylpropoxy)phenoxy]imidazo[1,5- a]pyridine; 2-[2-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5- yl]oxyphenoxy]ethoxy]ethanol; 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(3-methoxypropoxy)phenoxy]imidazo[1,5-a]pyridine; 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-7-[4-(trideuteriomethyl)-1,2,4-triazol-3- yl]imidazo[1,5-a]pyridine; 4-[3-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl]-1- methyl-piperazin-2-one; N-[3-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5- yl]oxyphenoxy]propyl]tetrahydrofuran-3-amine; 6-[3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl]-3-oxa-6- azabicyclo[3.1.1]heptane; 1-[4-[3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5- yl]oxyphenoxy]propyl]piperazin-1-yl]ethanone; 1-methyl-4-[3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl] piperazin-2-one; 6-(4-methyl-1,2,4-triazol-3-yl)-8-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo [1,5-a]pyridine; 7-[2-fluoro-4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[2-(4-piperidyloxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-[2-[(1-acetyl-4-piperidyl)oxy]ethoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-5-(4-methyl-1,2,4-triazol-3-yl)-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole; 5-(4-cyclopropyl-1,2,4-triazol-3-yl)-1-methyl-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole; 7-[2-fluoro-4-(2-pyrrolidin-3-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-[2-(1-acetylpyrrolidin-3-yl)oxyethoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[3-(2-oxa-5-azabicyclo[2.2.2]octan-5-yl)propoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 7-[4-[3-(3-ethylmorpholin-4-yl)propoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)propoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 7-[2-fluoro-4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)propoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 7-[2-fluoro-4-[3-[2-(hydroxymethyl)morpholin-4-yl]propoxy]phenoxy]-1-methyl-indazole- 5-carboxamide; 5-imidazol-1-yl-1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole; 1-methyl-5-(3-methylimidazol-4-yl)-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole; 5-[3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenoxy]propyl]-2-oxa-5- azabicyclo[2.2.2]octane; 5-[3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenoxy]propyl]-2-oxa-5- azabicyclo[2.2.1]heptane; 3-[3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenoxy]propyl]-6-oxa-3- azabicyclo[3.1.1]heptane; 6-[4-(6,8-dihydro-5H-imidazo[1,5-a]pyrazin-7-yl)phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-(2-methyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)phenoxy]indazole-5- carboxamide; 7-[4-[3-(2-ethylmorpholin-4-yl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 3-chloro-1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxamide; 7-[2-fluoro-4-(3-morpholino-3-oxo-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 7-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]-1- methyl-indazole-5-carboxamide; 7-[2-fluoro-4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 3-fluoro-1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxamide; 1-isopropyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-cyclopropyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 6-[4-[2-[[(1S,5R)-8-azabicyclo[3.2.1]octan-3-yl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[[(1R,5S)-8-acetyl-8-azabicyclo[3.2.1]octan-3-yl]oxy]ethoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 1-methyl-6-[4-[2-[[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3- yl]oxy]ethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-[[(1R,5S)-8-(2-methoxyacetyl)-8-azabicyclo[3.2.1]octan-3-yl]oxy]ethoxy]phenoxy]- 1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[2-[(1-methyl-4-piperidyl)oxy]ethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-[[1-(2-methoxyacetyl)-4-piperidyl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[[1-(2-hydroxyacetyl)-4-piperidyl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[[1-(cyclopropanecarbonyl)-4-piperidyl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-(1-acetylazetidin-3-yl)oxyethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-[2-[1-(2-methoxyacetyl)azetidin-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[1-(2-hydroxyacetyl)azetidin-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[1-(cyclopropanecarbonyl)azetidin-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 6-[4-[3-[4-(2-methoxyacetyl)piperazin-1-yl]propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1H-indazole-5-carboxamide; 1-(difluoromethyl)-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxamide; 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-(trideuteriomethyl)indazole-5- carboxamide; 1-methyl-6-[4-(3-tetrahydropyran-4-yloxycyclobutoxy)phenoxy]indazole-5-carboxamide; 7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-5-(4-methyl-1,2,4- triazol-3-yl)indazole; 2-[7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazol-5-yl]-1,3,4- oxadiazole; 7-(2,3-dihydrobenzofuran-5-yloxy)-5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazole; Azetidin-1-yl-[1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5- yl]methanone; 1-methyl-7-[4-[3-(2-oxopiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-5-pyridazin-3-yl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole; 7-[4-(2,2-difluoro-3-morpholino-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-cyclopropyl-6-[4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-3-oxo- propoxy]phenoxy]indazole-5-carboxamide; 1-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenyl]-3-methyl- imidazolidin-2-one; 6-(4-ethyl-1,2,4-triazol-3-yl)-8-[4-[3-(4-methylpiperazin-1- yl)propoxy]phenoxy]imidazo[1,5-a]pyridine; 1-[4-[3-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8- yl]oxyphenoxy]propyl]piperazin-1-yl]ethanone; 4-[3-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8- yl]oxyphenoxy]propyl]morpholine; 2-[4-[7-(4-cyclopropyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]ethanol; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-methyl- imidazolidin-2-one; 1-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenyl]pyrrolidin-2-one; 1-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenyl]-3-methyl- imidazolidin-2-one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-methyl-imidazol-2- one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(oxetan-3- ylmethyl)imidazolidin-2-one; 1-cyclopropyl-3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7- yl]oxyphenyl]imidazolidin-2-one; 5-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-5- azaspiro[2.4]heptan-4-one; 1-ethyl-3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]imidazolidin- 2-one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(2- methoxyethyl)imidazolidin-2-one; 1-(cyclopropylmethyl)-3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7- yl]oxyphenyl]imidazolidin-2-one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(oxetan-3- ylmethyl)imidazol-2-one; 1-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenyl]-3-(2- methoxyethyl)imidazolidin-2-one; 1-(cyclopropylmethyl)-3-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8- yl]oxyphenyl]imidazolidin-2-one; 3-[1-methyl-7-[4-(3-methyl-2-oxo-imidazol-1-yl)phenoxy]indazol-5-yl]triazole-4- carboxamide; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(1- methylcyclopropyl)imidazol-2-one; 7-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 5-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 1-cyclopropyl-6-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]indazole-5- carboxamide; and 1-cyclopropyl-6-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; or a pharmaceutically acceptable salt thereof. A further embodiment of present invention is (xxi) a process for the preparation of a compound having the structure of formula (Ia), (Ib), (Ic), or (Id) comprising one of the following steps: (a) Nucleophilic substitution or Mitsunobu reaction between a compound of formula VI VI and a compound of formula VII VII, provides compound of formula (Ia); (b) hydrolysis of Intermediate B Intermediate B with a base and coupling with ammonium chloride with a condensing reagent provides compound of formula (Ia), wherein the base is preferably LiOH, and the condensing reagent is preferably HATU / DIPEA; (c) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XI XI and a compound of formula VIIIA provides compound of formula (Ia); wherein the nucleophilic reagent is preferably selected from alcohol, amide, primary or secondary amine; (d) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XII XII and a compound of formula IIA, IIA hydrolysis with a base and coupling with ammonium chloride with a condensing reagent provides compound of formula (Ia), wherein the base is preferably LiOH, and the condensing reagent is preferably HATU / DIPEA; (e) Coupling between a compound of formula X and a compound of formula VIIA with a condensing reagent provides Compound of formula (Ib), wherein the condensing reagent is preferably HATU / DIPEA; (f) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XIV XIV and a compound of formula VII provides compound of formula (Ic); (g) Condensation of a compound of formula XVI XVI successively with (i) DMFDMA and (ii) a second reagent provides compound of formula (Ic), wherein when Z is NQ1, the second reagent is primary amine preferably selected from ethylamine and cyclopropylamine, when Z is O, the second agent is alcohol preferably methonal, when Z is S, the second reagent is Lawesson’s reagent; (h) Buchwald-Hartwig or copper catalyzed cross coupling of compound of formula XV XV with a compound of formula VIIA provides compound of formula (Id); wherein ring A is selected from, bond a is connected with carbonyl and bond b is connected with oxygen, ring B is selected from: bond a is connected with the five-membered hetero-aromatic ring and bond b is connected with oxygen, X is F, Cl, Br or I; LG1is a leaving group selected from Cl, Br, I, O-tosyl, and O-mesyl; Z is O, S, or NQ1, Q1is selected from C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, and C1-6alkoxyC1-6alkyl, preferably selected from methyl, trideuteriomethyl, ethyl, cyclopropyl, and methoxyethyl; R2, R3, R4, R6, L4, and L5, are as defined in any one of embodiments 1 to 19. A further embodiment of present invention is (xxii) a compound or a pharmaceutically acceptable salt thereof according to any one of embodiments (i) to (xx), when manufactured according to the process of embodiment (xxi). PHARMACEUTICAL COMPOSITIONS AND ADMINISTRATION Another embodiment provides pharmaceutical compositions or medicaments containing the compounds of the invention and a therapeutically inert carrier, diluent or excipient, as well as methods of using the compounds of the invention to prepare such compositions and medicaments. In one example, compounds of formula (I) may be formulated by mixing at ambient temperature at the appropriate pH, and at the desired degree of purity, with physiologically acceptable carriers, i.e., carriers that are non-toxic to recipients at the dosages and concentrations employed into a galenical administration form. The pH of the formulation depends mainly on the particular use and the concentration of compound, but preferably ranges anywhere from about 3 to about 8. In one example, a compound of formula (I) is formulated in an acetate buffer, at pH 5. In another embodiment, the compounds of formula (I) are sterile. The compound may be stored, for example, as a solid or amorphous composition, as a lyophilized formulation or as an aqueous solution. Compositions are formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners. The “effective amount” of the compound to be administered will be governed by such considerations, and is the minimum amount necessary to inhibit CDK8 and / or CDK19 kinase activities and kinase dependent down stream transcriptional effects. For example, such amount may be below the amount that is toxic to normal cells, or the mammal as a whole. In one example, the pharmaceutically effective amount of the compound of the invention administered parenterally per dose will be in the range of about 0.01 to 1000 (e.g., 0.01-100) mg / kg, alternatively about 0.01 to 200 (e.g., 0.1 to 20) mg / kg of patient body weight per day, with the typical initial range of compound used being 0.3 to 15 mg / kg / day. In another embodiment, oral unit dosage forms, such as tablets and capsules, preferably contain from about 1 to about 1000 (e.g., 25-100) mg of the compound of the invention. The compounds of the invention may be administered by any suitable means, including oral, topical (including buccal and sublingual), rectal, vaginal, transdermal, parenteral, subcutaneous, intraperitoneal, intrapulmonary, intradermal, intrathecal and epidural and intranasal, and, if desired for local treatment, intralesional administration. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration. The compounds of the present invention may be administered in any convenient administrative form, e.g., tablets, powders, capsules, solutions, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. Such compositions may contain components conventional in pharmaceutical preparations, e.g., diluents, carriers, pH modifiers, sweeteners, bulking agents, and further active agents. A typical formulation is prepared by mixing a compound of the present invention and a carrier or excipient. Suitable carriers and excipients are well known to those skilled in the art and are described in detail in, e.g., Ansel, Howard C., et al., Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lippincott, Williams & Wilkins, 2004; Gennaro, Alfonso R., et al. Remington: The Science and Practice of Pharmacy. Philadelphia: Lippincott, Williams & Wilkins, 2000; and Rowe, Raymond C. Handbook of Pharmaceutical Excipients. Chicago, Pharmaceutical Press, 2005. The formulations may also include one or more buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants, sweeteners, perfuming agents, flavoring agents, diluents and other known additives to provide an elegant presentation of the drug (i.e., a compound of the present invention or pharmaceutical composition thereof) or aid in the manufacturing of the pharmaceutical product (i.e., medicament). An example of a suitable oral dosage form is a tablet containing about 1 to 1000 (e.g., 25mg, 50mg, 100mg, 250mg, or 500mg) of the compound of the invention compounded with about 1 to 1000 (e.g., 90-30) mg anhydrous lactose, about 1 to 1000 (e.g., 5-40) mg sodium croscarmellose, about 1 to 1000 (e.g., 5-30mg) polyvinylpyrrolidone (PVP) K30, and about 1 to 1000 (e.g., 1-10 mg) magnesium stearate. The powdered ingredients are first mixed together and then mixed with a solution of the PVP. The resulting composition can be dried, granulated, mixed with the magnesium stearate and compressed to tablet form using conventional equipment. An example of an aerosol formulation can be prepared by dissolving the compound, for example 1 to 1000 (e.g., 5-400 mg), of the invention in a suitable buffer solution, e.g. a phosphate buffer, adding a tonicifier, e.g. a salt such sodium chloride, if desired. The solution may be filtered, e.g., using a 0.2 micron filter, to remove impurities and contaminants. An embodiment, therefore, includes a pharmaceutical composition comprising a compound of Formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof. In a further embodiment includes a pharmaceutical composition comprising a compound of Formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or excipient. Another embodiment includes a pharmaceutical composition comprising a compound of Formula (I) for use in the treatment of immune mediated diseases. The following embodiments illustrate typical compositions of the present invention, but serve merely as representative thereof. Composition A A compound of the present invention can be used in a manner known per se as the active ingredient for the production of tablets of the following composition: Per tablet Active ingredient 200 mg Microcrystalline cellulose 155 mg Corn starch 25 mg Talc 25 mg Hydroxypropylmethylcellulose 20 mg 425 mg Composition B A compound of the present invention can be used in a manner known per se as the active ingredient for the production of capsules of the following composition: Per capsule Active ingredient 100.0 mg Corn starch 20.0 mg Lactose 95.0 mg Talc 4.5 mg Magnesium stearate 0.5 mg 220.0 mg INDICATIONS AND METHODS OF TREATMENT The compounds of the invention can enhance anti-inflammatory cytokine IL-10 and down regulate some proinflammatory cytokines in activated myeloid cells. Accordingly, the compounds of the invention are useful for alleviating inflammation mediated by activated dendritic cells and macrophages. Compounds of the invention are useful for promoting Treg frequency in activated T cells. Alternatively, compounds of the invention are useful for damp T cell mediated immune response in which mediated by CDK8 and CDK19 in inflammatory setting. More broadly, the compounds can be used for the treatment of many immune mediated diseases such as Graft-versus-host disease, solid organ transplantation rejection, multiple sclerosis, rheumatoid arthritis, atopic dermatitis, psoriasis, amyotrophic lateral sclerosis and stroke that can benefit from above mechanisms. Another embodiment includes a method of treating or preventing immune mediated diseases in a mammal in need of such treatment, wherein the method comprises administering to said mammal a therapeutically effective amount of a compound of formula (I), a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof. Another embodiment includes a method of treating immune mediated diseases in a mammal in need of such treatment, wherein the method comprises administering to said mammal a therapeutically effective amount of a compound of formula (I), a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof. Immune mediated diseases includes but is not limited to Graft-versus-host disease, solid organ transplantation rejection, multiple sclerosis, rheumatoid arthritis, atopic dermatitis, psoriasis, amyotrophic lateral sclerosis and stroke. A further embodiment of present invention is (xxiv) a compound of the invention for use as therapeutically active substance. A further embodiment of present invention is (xxv) a compound of the invention for use in the treatment or immune mediated diseases. A further embodiment of present invention is (xxvi) the use of a compound of the invention for the treatment of immune mediated diseases. A further embodiment of present invention is (xxvii) the use of a compound of the invention for the inhibition of CDK8 and / or CDK19. A further embodiment of present invention is (xxviii) the use of a compound of the invention for the preparation of a medicament for the treatment of immune mediated diseases. A further embodiment of present invention is (xxix) the use of a compound of the invention for the preparation of a medicament for the inhibition of CDK8 and / or CDK19. A further embodiment of present invention is (xxx) a method for the treatment of immune mediated diseases, which method comprises administering an effective amount of a compound of the invention. A further embodiment of present invention is (xxxi) the use of according to any one of embodiments (xxiv) to (xxix), or the method according to (xxx), wherein the immune mediated diseases is Graft-versus-host disease, solid organ transplantation rejection, multiple sclerosis, rheumatoid arthritis, atopic dermatitis, psoriasis, amyotrophic lateral sclerosis, or stroke. SYNTHESIS The compounds of the present invention can be prepared by any conventional means. Suitable processes for synthesizing these compounds as well as their starting materials are provided in the schemes below and in the examples. All substituents, in particular, R1to R6, L1 to L5, and A1to A4are as defined above unless otherwise indicated. Furthermore, and unless explicitly otherwise stated, all reactions, reaction conditions, abbreviations and symbols have the meanings well known to a person of ordinary skill in organic chemistry. General synthetic routes for preparing the compound of the invention are shown in scheme 1-4. Scheme 1

[0002] wherein X is F, Cl, Br or I; each of PG1and PG2is a protecting group, for example Ac or Bn or H; each of LG1and LG2is a leaving group, for Example Cl, Br, I, O-tosyl or O-mesyl; ring A is selected from: wherein bond a is connected with carbonyl and bond b is connected with oxygen. A compound of formula (Ia) can be prepared according to the synthetic route outlined in Scheme 1: a) Coupling of a compound of formula IIA and a compound of formula IIB under Cu catalyzed condition or Mitsunobu reaction provides a compound of formula III b) Hydrolysis of a compound of formula III with a base, such as LiOH, NaOH and KOH; c) Coupling with ammonium chloride with a condensing reagent such as HATU provides a compound of formula V; d) Removal of the protecting group with transition metal catalyst (for example Pd / C), base (for example K2CO3), or acid (for example, TFA) provides a compound of formula VI; e) Nucleophilic substitution or Mitsunobu reaction between a compound of formula VI and a compound of formula VIIVIIprovides compound of formula (Ia). Compound of formula (Ia) can also be synthesized from compound of formula III via: f) Removal of the protecting group with reagent such as catalyst (for example Pd / C), base (for example K2CO3), or acid (for example, TFA) provides Intermediate A; Intermediate Ag) Nucleophilic substitution or Mitsunobu reaction between Intermediate A and compound of formula VII provides Intermediate B; Intermediate B h) Hydrolysis of Intermediate B with a base, such as LiOH, i) Coupling with ammonium chloride with a condensing reagent such as HATU / DIPEA provides compound of formula (Ia). Compound of formula (Ia) can also be synthesized from compound of formula VI via: l) Nucleophilic substitution or Mitsunobu reaction between a compound of formula VI and a compound of formula VIII VIIIprovides a compound of formula XI; m) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XI and a compound of formula VIIIA VIIIA provides compound of formula (Ia). Compound of formula (Ia) can also be synthesized from Intermediate A via: j) Nucleophilic substitution or Mitsunobu reaction between Intermediate A and compound of a compound of formula VIII provides a compound of formula IV; k) Nucleophilic substitution or Mitsunobu reaction between compound of formula IV and a compound of formula VIIA VIIAprovides Intermediate B; h) Hydrolysis of Intermediate B with a base, such as LiOH, i) Coupling with ammonium chloride with a condensing reagent such as HATU / DIPEA provides compound of formula (Ia). Compound of formula (Ia) can also be synthesized from a compound of formula XII via: q) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XII and a compound of formula IIA r) Hydrolysis of methyl ester with a base, such as LiOH, and s) Coupling with ammonium chloride with a condensing reagent such as HATU / DIPEA provides compound of formula (Ia). Compound of formula (Ib) can be synthesized from a compound of formula VI via: n) Michael addition with a compound of formula VIIIB provides a compound of formula IX; o) Removal of the protecting group with reagent such as catalyst (for example Pd / C) or acid (for example, TFA) provides a compound of formula X; p) Coupling between a compound of formula X and a compound of formula VIIA with a condensing reagent such as HATU provides Compound of formula (Ib). Scheme 2

[0003] Id wherein each of PG1and PG2is a protecting group, for example Ac or Bn or H; each of LG1and LG2is a leaving group, for Example Cl, Br, I, O-tosyl or O-mesy; Z is O, S, or NQ1, wherein Q1is selected from C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, and C1-6alkoxyC1-6alkyl, preferably selected from methyl, trideuteriomethyl, ethyl, cyclopropyl, and methoxyethyl; ring B is selected from: wherein bond a is connected with the five-membered hetero-aromatic ring and bond b is connected with oxygen. Compound of formula (Ic) can be prepared from Intermediate A according to the synthetic route outlined in Scheme 2: a) Hydrazinolysis of Intermediate A with hydrazine monohydrate provides compound of formula XIII , b) Condensation of XIII successively with (i) DMFDMA and (ii) a primary amine (wherein Z is N; for example ethylamine, cyclopropylamine), alcohol (wherein Z is O; for example methonal), or Lawesson’s reagent (wherein Z is S) provides compound of formula XIV; c) Nucleophilic substitution or Mitsunobu reaction between compound of formula XIV and VII provides compound of formula (Ic). Compound of formula (Ic) can also be synthesized from Intermediate B via: d) Hydrazinolysis of Intermediate B with hydrazine monohydrate provides compound of formula XVI; e) Condensation of XVI successively with (i) DMFDMA and (ii) a primary amine (wherein Z is N; for example ethylamine, cyclopropylamine), alcohol (wherein Z is O; for example methonal), or Lawesson’s reagent (wherein Z is S) provides compound of formula (Ic). Compound of formula (Id) can be synthesized from compound of formula XIV via: f) Triflation of compound of formula XIV with trifluoromethanesulfonic anhydride provides compound of formula XV; g) Buchwald-Hartwig or copper catalyzed cross coupling of compound of formula XV with a compound of formula VIIA provides compound of formula (Id). Scheme 3 Intermediate A1wherein PG1is a protecting group, for example Bn; each of X1and X2is a halogen atom or pseudo halogen, for Example Cl, Br, I, O-tosyl or O-triflyl. In some aspects, Intermediate A in Scheme 1 can be prepared as compound of formula Intermediate A1 Intermediate A1according to the synthetic route outlined in Scheme 3: a) Buchwald-Hartwig or copper catalyzed cyanidation of a compound of formula XVIIXVIIprovides a compound of formula XVIII; XVIIIb) Copper catalyzed cross coupling or SNAr substitution of a compound of formula XVIII with a compound of formula XIX provides a compound of formula XX; c) Hydrogenation of a compound of formula XX with a transitional metal catalyst, for example Pd / C, Pd(OH)2 / C, PtO2 or Raney Nickel provides compound of formula XXI; d) Condensation of compound of formula XXI with acid anhydride, for example acetyl anhydride, formic acid / acetyl anhydride mixture and consequential hydrolysis under basic condition provides compound of formula Intermediate A1. Scheme 4 wherein PG1is a protecting group, for example Bn; X1or X2is a halogen atom or pseudo halogen, for example Cl, Br, I, O-tosyl or O-triflyl; R8cis independently selected from H, C1-6alkyl, deuterated C1-6alkyl or C3-10cycloalkyl. In some aspects, Intermediate A in Scheme 1 can be prepared as compound of formula Intermediate A2 Intermediate A2according to the synthetic route outlined in Scheme 4: a) Copper catalyzed cross coupling or SNAr substitution of compound of formula XXII with compound of formula XXIII provides compound of formula XXIV; b) Reduction of compound of formula XXIV with a reductant, for example BH3or NaBH4provides compound of formula XXV; c) Condensation of compound of formula XXV with acid anhydride, for example acetyl anhydride, formic acid / acetyl anhydride mixture provide compound of formula XXVI; d) Alkoxycarbonylation of compound of formula XXVI with a palladium catalyst such as Pd(dppf)Cl2 under CO atmosphere provides compound of formula XXVII; e) Hydrogenation of XXVII with a transitional metal catalyst, for example Pd / C, Pd(OH)2 / C, PtO2 or Raney Nickel provides compound of formula Intermediate A2. EXAMPLES The invention will be more fully understood by reference to the following examples. They should not, however, be construed as limiting the scope of the invention. ABBREVIATIONS The invention will be more fully understood by reference to the following examples. They should not, however, be construed as limiting the scope of the invention. Abbreviations used herein are as follows: ACN or MeCN: acetonitrile Ac: acetyl aq.: aqueous BAIB: (diacetoxyiodo)benzene BMPPO: N-benzyl-N'-(4-methyl-2-phenyl-phenyl)oxamide BPPO: N,N'-bis(2-phenylphenyl)oxamide Bn: benzyl BOC or Boc: tert-butyloxycarbonyl CDCl3: deuterated chloroform CD3OD: deuterated methanol DEAD: diethyl azodicarboxylate DIAD: diisopropyl azodicarboxylate DIPEA or DIEA: N, N-diethylpropylamine DMAP: 4-dimethylaminopyridine DMF: N, N-dimethyl formamide DMA or DMAc: N, N-dimethylacetamide DCM: dichloromethane DCE: dichloroethane DIBAL-H diisobutylaluminium hydride DMSO: dimethyl sulfoxide DMFDMA: dimethylformamide Dimethylacetal dppf: 1,1'-bis(diphenylphosphino)ferrocene EDCI: N-Ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride EtOAc or EA: ethyl acetate EtOH: ethanol FA: formic acid FRET: fluorescence resonance energy transfer HATU: (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5- b]pyridinium 3-oxid hexafluorophosphate) hr(s) or h: hour(s) HPLC: high performance liquid chromatography HOBt: N-hydroxybenzotriazoleiPrOH: isopropanol LDA: lithium diisopropylamide MS (ESI): mass spectroscopy (electron spray ionization) MeOH: methanol m-CPBA: meta-chloroperoxybenzoic acid min(s) : minute(s) NCS: N-Chlorosuccinimide NMR: nuclear magnetic resonance obsd.: observed Pd / C: palladium on carbon PMB: p-methoxybenzyl prep. HPLC: preparative high performance liquid chromatography PyBOP: benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate rt or rt: rt sat.: saturated SelectFluor®: 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) SEM: trimethylsilylethoxymethyl SFC: supercritical fluid chromatography tBu: tert-butyl TBDPS: tert-butyldiphenylsilyl TBDMS or TBS: tert-butyldimethylsilyl TBAF: tetra-n-butylammonium fluoride TEA: triethylamine TFA: trifluoroacetic acid THF: tetrahydrofuran TLC: thin-layer chromatography Tf: trifluoromethanesulfonyl TFAA: trifluoroacetic anhydride T3P: propylphosphonic anhydride Ts: p-toluenesulfonyl GENERAL EXPERIMENTAL CONDITIONS Intermediates and final compounds were purified by flash chromatography using one of the following instruments: i) Biotage SP1 system and the Quad 12 / 25 Cartridge module. ii) ISCO combi-flash chromatography instrument. Silica gel brand and pore size: i) KP-SIL 60 Å, particle size: 40-60 µm; ii) CAS registry NO: Silica Gel: 63231-67-4, particle size: 47-60 micron silica gel; iii) ZCX from Qingdao Haiyang Chemical Co., Ltd, pore: 200-300 or 300-400. Intermediates and final compounds were purified by prep. HPLC on reversed phase column using XBridgeTMPrep-C18 (5 µm, OBDTM 30 × 100 mm) column, SunFireTMPrep-C18 (5 µm, OBDTM30 × 100 mm) column, Phenomenex Synergi-C18 (10 µm, 25 × 150 mm) or Phenomenex Gemini-C18 (10 µm, 25 × 150 mm), Waters AutoP purification System (Sample Manager 2767, Pump 2525, Detector: Micromass ZQ and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water; acetonitrile and 0.1% FA in water or acetonitrile and 0.1% TFA in water), or Gilson-281 purification System (Pump 322, Detector: UV 156, solvent system: acetonitrile and 0.05% ammonium hydroxide in water; acetonitrile and 0.225% FA in water; acetonitrile and 0.05% HCl in water; acetonitrile and 0.075% TFA in water; or acetonitrile and water). For SFC chiral separation, intermediates were separated by chiral column (Daicel chiralpak IC, 5 µm, 30 × 250 mm), AS (10 µm, 30 × 250 mm) or AD (10 µm, 30 × 250 mm) using Mettler Toledo Multigram III system SFC, Waters 80Q preparative SFC or Thar 80 preparative SFC, solvent system: CO2 and IPA (0.5% TEA in IPA) or CO2 and MeOH (0.1% NH3∙H2O in MeOH), back pressure 100bar, detection UV@ 254 or 220 nm. LC / MS spectra of compounds were obtained using a LC / MS (WatersTMAlliance 2795- Micromass ZQ, Shimadzu Alliance 2020-Micromass ZQ or Agilent Alliance 6110-Micromass ZQ), LC / MS conditions were as follows (running time 3 or 1.5 mins): Acidic condition I: A: 0.1% TFA in H2O; B: 0.1% TFA in acetonitrile; Acidic condition II: A: 0.0375% TFA in H2O; B: 0.01875% TFA in acetonitrile; Basic condition I: A: 0.1% NH3·H2O in H2O; B: acetonitrile; Basic condition II: A: 0.025% NH3·H2O in H2O; B: acetonitrile; Neutral condition: A: H2O; B: acetonitrile. Mass spectra (MS): generally only ions which indicate the parent mass are reported and unless otherwise stated the mass ion quoted is the positive mass ion (MH)+. NMR Spectra were obtained using Bruker Avance 400 MHz. The microwave assisted reactions were carried out in a Biotage Initiator Sixty microwave synthesizer. All reactions involving air-sensitive reagents were performed under an argon or nitrogen atmosphere. Reagents were used as received from commercial suppliers without further purification unless otherwise noted. PREPARATIVE EXAMPLES Intermediate 1a Methyl 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylate Int-1a Step 1: methyl 7-bromo-1-methyl-indazole-5-carboxylate To a solution of methyl 7-bromo-1H-indazole-5-carboxylate (5.8 g, 22.58 mmol) and Cs2CO3 (14.7 g, 45.16 mmol) in ACN (60 mL) was added iodomethane (3.2 g, 22.58 mmol). The mixture was stirred at 20 °C for 2 h. The mixture was diluted with water (30 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum. The crude was purified by flash chromatography to give methyl 7-bromo-1-methyl- indazole-5-carboxylate (3.28 g) as yellow solid. MS [M+H]+: 269.0.1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (d, J = 1.2 Hz, 1 H), 8.33 (s, 1 H), 8.08 (d, J = 1.2 Hz, 1 H), 4.36 (s, 3 H), 3.88 (s, 3 H). Step 2: methyl 7-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxylate A flask was dried by heating with a heat gun in vacuum. To this flask was added successively 4-benzyloxyphenol (2.1 g, 10.34 mmol), 7-bromo-1-methyl-indazole-5-carboxylate (1.9 g, 6.88 mmol), CuI (0.7 g, 3.44 mmol), BPPO (0.6 g, 1.38 mmol), K3PO4 (4.4 g, 20.63 mmol) and DMF (20 mL). The mixture was degassed and purged with N2gas for four times, and then stirred at 90 °C for 16 h under N2. The mixture was cooled, diluted with water (30 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum. The crude was purified by flash chromatography to give methyl 7-(4- benzyloxyphenoxy)-1-methyl-indazole-5-carboxylate (1.56 g) as brown solid. MS [M+H]+: 389.1. Step 3: methyl 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylate (Int-1a) To a 100 mL flask were added methyl 7-(4-benzyloxyphenoxy)-1-methyl-indazole-5- carboxylate (420.0 mg, 1.08 mmol), methanol (5 mL) and Pd / C (200 mg, 10% loading) in one portion. The mixture was degassed and purged with H2 three times and then stirred at 20 °C for 2 h under H2 atmosphere (50 psi). The suspension was filtered through a pad of Celite and the cake was washed with methanol. The solvent was removed in vacuum. The residue was purified by prep. TLC to give crude methyl 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylate (260.0 mg) which was used in the next step without further purification. MS [M+H]+: 299.1. Intermediate 1b Methyl 6-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylate Methyl 6-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylate (Int-1b) was prepared in analogy to Int-1a, by replacing 7-bromo-1H-indazole-5-carboxylate with methyl 6-bromo-1H- indazole-5-carboxylate in step 1. MS [M+H]+: 299.0. Intermediate 1c Methyl 7-(3-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate Methyl 7-(3-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate (Int-1c) was prepared in analogy to Int-1a, by replacing 4-benzyloxyphenol with 4-benzyloxy-3-fluoro- phenol in step 2. MS [M+H]+: 317.0. Intermediate 1d Methyl 7-(3-chloro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate Methyl 7-(3-chloro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate (Int-1d) was prepared in analogy to Int-1a, by replacing 4-benzyloxyphenol with 4-benzyloxy-3-chloro- phenol in step 2. MS [M+H]+: 333.2. Intermediate 1e Methyl 7-(4-hydroxyphenoxy)-1-(2-trimethylsilylethoxymethyl)indazole-5-carboxylate Methyl 7-(4-hydroxyphenoxy)-1-(2-trimethylsilylethoxymethyl)indazole-5-carboxylate (Int-1e) was prepared in analogy to Int-1a, by replacing iodomethane with 2- (trimethylsilyl)ethoxymethyl chloride in step 1. MS [M+H]+: 415.2. Intermediate 1f Methyl 6-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate Methyl 6-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate (Int-1f) was prepared in analogy to Int-1a, by replacing 4-benzyloxyphenol with 4-benzyloxy-2-fluoro- phenol in step 2. MS [M+H]+: 317.1. Intermediate 1g Methyl 6-(3-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate Methyl 6-(3-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate (Int-1g) was prepared in analogy to Int-1a, by replacing 4-benzyloxyphenol with 4-benzyloxy-3-fluoro- phenol in step 2. MS [M+H]+: 317.1. Intermediate 1h Methyl 7-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate Methyl 7-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate (Int-1 h) was prepared in analogy to Int-1a, by replacing 4-benzyloxyphenol with 4-benzyloxy-2-fluoro- phenol in step 2. MS [M+H]+: 317.1. Intermediate 1i Methyl 7-(2-chloro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate Methyl 7-(2-chloro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxylate (Int-1i) was prepared in analogy to Int-1a, by replacing 4-benzyloxyphenol with 2-chloro-4-[(4- methoxyphenyl)methoxy]phenol in step 2 and Pd / C-methanol with neat TFA in step 3. MS [M+H]+: 330.0. Intermediate 2a Methyl 8-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-6-carboxylate Int-2a Step 1: 3-(4-benzyloxyphenoxy)-5-bromo-pyridine-2-carbonitrile To a mixture of 5-bromo-3-fluoro-pyridine-2-carbonitrile (10.0 g, 49.75 mmol) and 4- benzyloxyphenol (10.0 g, 49.75 mmol) in DMF (100 mL) was added potassium carbonate (20.6 g, 149.2 mmol). The mixture was stirred at 60 °C for 16 h, cooled and filtered. The filtrate was concentrated in vacuum to give crude 3-(4-benzyloxyphenoxy)-5-bromo-pyridine-2-carbonitrile (18.0 g) which was used in the next step directly without further purification. MS [M+H]+: 381.3. Step 2: [3-(4-benzyloxyphenoxy)-5-bromo-2-pyridyl]methanamine To a mixture of 3-(4-benzyloxyphenoxy)-5-bromo-pyridine-2-carbonitrile (17.0 g, 44.59 mmol) in THF (170 mL) was added BH3•THF (1M, 223.0 mL, 222.9 mmol). The resulting mixture was stirred at 80 °C for 1 h to give a black mixture. The mixture was concentrated in vacuum. The crude was purified by reversed-phase chromatography to give [3-(4- benzyloxyphenoxy)-5-bromo-2-pyridyl]methanamine (1.8 g) as white solid. MS [M+H]+: 385.4. Step 3: 8-(4-benzyloxyphenoxy)-6-bromo-imidazo[1,5-a]pyridine To a 250 mL round-bottom flask were added formic acid (60.0 mL, 1.82 mmol) and acetic anhydride (72.0 mL, 1.82 mmol). The mixture was warmed up to 50 °C, stirred for 2 h and then cooled to 20 °C. [3-(4-benzyloxyphenoxy)-5-bromo-2-pyridyl]methanamine (0.7 g, 1.82 mmol) was added. The resulting mixture was stirred at 20 °C for 1 h, then warmed up to 35 °C and stirred for another 1 h. The mixture was concentrated in vacuum. The crude was purified by reversed-phase chromatography to give 8-(4-benzyloxyphenoxy)-6-bromo-imidazo[1,5- a]pyridine (300.0 mg) as orange solid. MS [M+H]+: 395.1. Step 4: methyl 8-(4-benzyloxyphenoxy)imidazo[1,5-a]pyridine-6-carboxylate To a mixture of 1,1'-bis(diphenylphosphino)ferrocenepalladium dichloride (150.0 mg, 0.18 mmol), 8-(4-benzyloxyphenoxy)-6-bromo-imidazo[1,5-a]pyridine (350.0 mg, 0.89 mmol) in DMF (8 mL) was added triethylamine (0.4 mL, 2.66 mmol). The resulting mixture was degassed and purged with CO for three times and then stirred at 80 °C for 12 h under CO (50 Psi). The mixture was concentrated in vacuum, added with water (20 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuum. The crude product was purified by reversed-phase chromatography to give methyl 8-(4-benzyloxyphenoxy)imidazo[1,5-a]pyridine-6-carboxylate (200.0 mg) as light brown solid. MS [M+H]+: 375.1. Step 5: methyl 8-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-6-carboxylate (Int-2a) To a mixture of methyl 8-(4-benzyloxyphenoxy)imidazo[1,5-a]pyridine-6-carboxylate (180.0 mg, 0.48 mmol) in methanol (5 mL) was added Pd / C (20 mg, 10% loading) in one portion at 25 °C. the mixture was degassed and purged with H2 for 3 times and then stirred at 25 °C for 1 h under H2atmosphere (50 psi). The suspension was filtered through a pad of Celite. The cake was washed with MeOH. The combined filtrate was concentrated in vacuum to give crude methyl 8-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-6-carboxylate (108.0 mg, 0.38 mmol) as off-white solid, which was used in the next step without further purification. MS [M+H]+: 285.1. Intermediate 2b Methyl 8-(4-hydroxyphenoxy)-1-methyl-imidazo[1,5-a]pyridine-6-carboxylate Methyl 8-(4-hydroxyphenoxy)-1-methyl-imidazo[1,5-a]pyridine-6-carboxylate (Int-2b) was prepared in analogy to Int-2a, by replacing BH3•THF with methylmagnesium bromide THF solution in step 2. MS [M+H]+: 299.0. Intermediate 3a Methyl 5-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carboxylate Step 1: methyl 2-bromo-6-cyano-pyridine-4-carboxylate Methyl 2,6-dibromopyridine-4-carboxylate (3.0 g, 10.17 mmol) was dissolved in DMF (30 mL). To this solution was added copper(I) cyanide (1.4 g, 15.26 mmol) in one portion. The resulting mixture was degassed, backfilled with N2 and stirred at 90 °C for 12 h. The mixture was poured into water and extracted with ethyl acetate. The combined organic layer was washed with brine and concentrated in vacuum. The residue was purified by column chromatography to give methyl 2-bromo-6-cyano-pyridine-4-carboxylate (478.0 mg) as light yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 9.28 (d, J = 5.2Hz, 1 H), 8.31 (d, J = 5.2Hz, 1 H), 3.96 (s, 4 H). Step 2: methyl 2-(4-benzyloxyphenoxy)-6-cyano-pyridine-4-carboxylate To a mixture of 2-bromo-6-cyano-pyridine-4-carboxylate (2.3 g, 9.54 mmol) and 4- benzyloxyphenol (2.3 g, 11.45 mmol) in DMF (30 mL) was added Cs2CO3(6.2 g, 19.08 mmol). The resulting mixture was stirred at 20 °C for 0.3 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give methyl 2-(4- benzyloxyphenoxy)-6-cyano-pyridine-4-carboxylate (1.1 g) as white solid. MS [M+H]+: 361.2. Step 3: methyl 2-(aminomethyl)-6-(4-hydroxyphenoxy)pyridine-4-carboxylate To a mixture of methyl 2-(4-benzyloxyphenoxy)-6-cyano-pyridine-4-carboxylate (330.0 mg, 0.92 mmol) and HCl (0.6 mL, 7.01 mmol) in methanol (10 mL) was added Pd / C (50 mg, 10% loading) at 25 °C. The mixture was degassed and purged with H2 (20 psi) three times, stirred at 25 °C for 12 h and filtered through a Celite pad. The filtrate was concentrated in vacuum to give methyl 2-(aminomethyl)-6-(4-hydroxyphenoxy)pyridine-4-carboxylate (330 mg) as yellow oil. MS [M+H]+: 275.1. Step 4: methyl 5-(4-acetoxyphenoxy)imidazo[1,5-a]pyridine-7-carboxylate To a 10 mL round-bottom flask was added acetyl acetate (1.2 mL) followed by formic acid (1 mL). The mixture was warmed up to 50 °C, stirred for 2h and then cooled to 20 °C. To this solution was added methyl 2-(aminomethyl)-6-(4-hydroxyphenoxy)pyridine-4-carboxylate (330.0 mg, 1.2 mmol). The resulting mixture was stirred at 20 °C for 1 h, then warmed up to 40 °C and stirred for 12 h. The mixture was concentrated in vacuum. The crude methyl 5-(4- acetoxyphenoxy)imidazo[1,5-a]pyridine-7-carboxylate (328.0 mg) was used in the next step without further purification. MS [M+H]+: 327.2. Step 5: methyl 5-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carboxylate (Int-3a) To a 100 mL round-bottom flask were added methyl 5-(4-acetoxyphenoxy)imidazo[1,5- a]pyridine-7-carboxylate (328.0 mg, 1.01 mmol), K2CO3 (208.4 mg, 1.51 mmol) and methanol (5 mL). The mixture was stirred at 25 °C for 1 h and filtered. The filtrate was concentrated in vacuum. The crude methyl 5-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carboxylate (270.0 mg) was used in the next step without further purification. MS [M+H]+: 285.3. Intermediate 3b Methyl 5-(4-hydroxyphenoxy)-3-methyl-imidazo[1,5-a]pyridine-7-carboxylate Methyl 5-(4-hydroxyphenoxy)-3-methyl-imidazo[1,5-a]pyridine-7-carboxylate (Int-3b) was prepared in analogy to Int-3a, by replacing formic acid with p-toluenesulfonic acid in step 4. MS [M+H]+: 299.0. Intermediate 3c Methyl 5-(2-fluoro-4-hydroxy-phenoxy)imidazo[1,5-a]pyridine-7-carboxylate Step1: methyl 2-(4-benzyloxy-2-fluoro-phenoxy)-6-bromo-pyridine-4-carboxylate To a 250 mL flask were added methyl 2,6-dibromopyridine-4-carboxylate (10.0 g, 33.91 mmol) and DMF (50 mL).4-(benzyloxy)-2-fluorophenol (7.4 g, 33.91 mmol) and Cs2CO3 (22.0 g, 67.52 mmol) were added at 25 °C. The mixture was stirred at 20 °C for 12 h and diluted with water (150 mL). The mixture was extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4and filtrated. The filtrate was concentrated in vacuum. The crude product was purified by column chromatography to give methyl 2-(4-benzyloxy-2- fluoro-phenoxy)-6-bromo-pyridine-4-carboxylate (6.6 g) as white solid. MS [M+H]+: 432.0.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.73 (d, J = 0.8Hz, 1 H), 7.48 - 7.40 (m, 5 H), 7.39 - 7.33 (m, 1 H), 7.14 (t, J = 9.2Hz, 1 H), 6.84 (dd, J = 12.0, 2.8Hz, 1 H), 6.81 - 6.77 (m, 1 H), 5.07 (s, 2 H), 3.96 (s, 3 H) . Step 2: methyl 2-(4-benzyloxy-2-fluoro-phenoxy)-6-cyano-pyridine-4-carboxylate To a 100 mL flask were added methyl 2-(4-benzyloxy-2-fluoro-phenoxy)-6-bromo- pyridine-4-carboxylate (3.0 g, 6.94 mmol) and DMF (30 mL). Then dicyanocopper (4.0 g, 34.83 mmol) was added. The mixture was stirred at 80 °C for 12 h, cooled and diluted with water (50 mL). The mixture was extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and filtrated. The filtrate was concentrated in vacuum. The residue was purified by column chromatography to give methyl 2-(4-benzyloxy-2-fluoro-phenoxy)-6-cyano-pyridine-4- carboxylate (1.5 g) as yellow solid. MS [M+H]+: 379.1. Step 3: methyl 2-(aminomethyl)-6-(2-fluoro-4-hydroxy-phenoxy)pyridine-4-carboxylate To a 100 mL flask were added methyl 2-(4-benzyloxy-2-fluoro-phenoxy)-6-cyano-pyridine- 4-carboxylate (1.5 g, 3.96 mmol) and methanol (20 mL). Then Pd / C (0.8 g, 10% loading) was added in one portion under argon atmosphere. The suspension was degassed and purged with H2 three times. The resulting mixture was stirred at 25 °C for 24 h under H2 atmosphere (20 psi) and filtered through a Celite pad. The cake was washed with MeOH. The combined filtrate was concentrated to dryness. The residue was purified by reversed-phase chromatography to give methyl 2-(aminomethyl)-6-(2-fluoro-4-hydroxy-phenoxy)pyridine-4-carboxylate (570.0 mg) as light yellow solid. MS [M+H]+: 293.1. Step 4: methyl 5-(2-fluoro-4-formyloxy-phenoxy)imidazo[1,5-a]pyridine-7-carboxylate To a 250 mL flask were added acetyl acetate (42.0 mL, 1.92 mmol) and formic acid (30.0 mL, 1.92 mmol). The mixture was warmed up to 50 °C, stirred for 2h and then cooled to 20 °C. Then methyl 2-(aminomethyl)-6-(2-fluoro-4-hydroxy-phenoxy)pyridine-4-carboxylate (560.0 mg, 1.92 mmol) was added. The mixture was stirred at 20 °C for 1 h, then warmed up to 40 °C and stirred for 12 h. The mixture was concentrated in vacuum to give crude methyl 5-(2-fluoro- 4-formyloxy-phenoxy)imidazo[1,5-a]pyridine-7-carboxylate (450.0 mg) as brown solid. MS [M+H]+: 331.1. Step 5: methyl 5-(2-fluoro-4-hydroxy-phenoxy)imidazo[1,5-a]pyridine-7-carboxylate (Int- 3c) To a 40 mL vial were added methyl 5-(2-fluoro-4-formyloxy-phenoxy)imidazo[1,5- a]pyridine-7-carboxylate (450.0 mg, 1.36 mmol), K2CO3 (564.0 mg, 4.09 mmol) and methanol (5 mL). The mixture was stirred at 25 °C for 1 h and filtered. The filtrate was concentrated in vacuum to give methyl 5-(2-fluoro-4-hydroxy-phenoxy)imidazo[1,5-a]pyridine-7-carboxylate (400.0 mg) as light yellow solid. MS [M+H]+: 303.1. Intermediate 4a 6-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxamide Int-4a Step 1: methyl 6-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxylate A flask was dried by heating with a heat gun in vacuum. To this flask were added successively 4-benzyloxyphenol (3.6 g, 18.00 mmol), methyl 6-bromo-1-methyl-indazole-5- carboxylate (4.1 g, 15.00 mmol), CuI (0.29 g, 1.50 mmol), BMPPO (0.52 g, 1.50 mmol), K3PO4 (6.4 g, 30.00 mmol) and DMSO (15 mL). The mixture was degassed and purged with N2gas for four times, and then stirred at 120 °C for 16 h under N2. After cooling to rt, the mixture was diluted with ethyl acetate and filtrated through silica gel and kieselguhr. The filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give methyl 6-(4- benzyloxyphenoxy)-1-methyl-indazole-5-carboxylate (4.99 g) as yellow solid. MS [M+H]+: 389.3. Step 2: 6-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxylic acid To a solution of methyl 6-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxylate (4.99 g, 12.85 mmol) in methanol (40 mL) and water (8 mL) was added LiOH•H2O (1.62 g, 38.54 mmol). The solution was stirred at 50 °C for 2 h. After cooling to rt, the mixture was adjusted to pH = 1-2 with 4 M HCl. The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum to give crude 6-(4- benzyloxyphenoxy)-1-methyl-indazole-5-carboxylic acid (4.61 g) as white solid. MS [M+H]+: 375.2. Step 3: 6-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxamide To a 250 mL flask was added 6-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxylic acid (4.61 g, 12.31 mmol) followed by successive addition of DMF (20 mL), NH4Cl (3.3 g, 61.57 mmol), HATU (7.02 g, 18.47 mmol) and DIEA (16.0 g, 123.13 mmol). The resulting mixture was stirred at 20 °C for 2 h. The reaction was quenched with water. The precipitate was collected and dried to give 6-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxamide (3.73 g) as yellow solid. MS [M+H]+: 374.3. Step 4: 6-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxamide (Int-4a) To a 250 mL flask were added 6-(4-benzyloxyphenoxy)-1-methyl-indazole-5-carboxamide (4.6 g, 12.32 mmol) and methanol (100 mL) and then Pd / C (920 mg, 10% loading) in one portion. The mixture was degassed and purged with H2three times and then stirred at 20 °C for 14 h under H2 ballon. The suspension was filtered through a pad of Celite and the cake was washed with methanol. The solvent was removed in vacuum to give crude 6-(4- hydroxyphenoxy)-1-methyl-indazole-5-carboxamide (3.43 g) which was used in the next step without further purification. MS [M+H]+: 284.0. Intermediate 4b 6-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxamide 6-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxamide (Int-4b) was prepared in analogy to Int-4a, by replacing 4-benzyloxyphenol with 4-benzyloxy-2-fluoro-phenol in step 1. MS [M+H]+: 302.0. Intermediate 4c 1-cyclopropyl-6-(4-hydroxyphenoxy)indazole-5-carboxamide 1-cyclopropyl-6-(4-hydroxyphenoxy)indazole-5-carboxamide (Int-4c) was prepared in analogy to Int-4a, by replacing methyl 6-bromo-1-methyl-indazole-5-carboxylate with Int-32a in step 1. MS [M+H]+: 310.2. Intermediate 5a 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxamide Int-1a Int-5a Step 1: 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylic acid To a solution of Int-1a (50.0 mg, 0.17 mmol) in methanol (1 mL) and water (2 mL) was added LiOH•H2O (28.1 mg, 0.67 mmol). The solution was stirred at 25 °C for 5 h and concentrated in vacuum to remove methanol. The pH of the aqueous residue was adjusted to 1-2 with 4 M HCl and concentrated in vacuum. The residue was purified by prep. HPLC to give 7- (4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylic acid (40.0 mg) as white solid. MS [M+H]+: 285.2. Step 2: 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxamide (Int-5a) To an 8 mL tube were added 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxylic acid (40.0 mg, 0.14 mmol), DMF (2 mL), NH4Cl (37.6 mg, 0.70 mmol), HATU (107.0 mg, 0.28 mmol) and DIEA (54.6 mg, 0.42 mmol). The resulting yellow mixture was stirred at 20 °C for 2 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed- phase chromatography to give 7-(4-hydroxyphenoxy)-1-methyl-indazole-5-carboxamide (40.0 mg) as yellow solid. MS [M+H]+: 284.2. Intermediate 5b 5-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carboxamide 5-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carboxamide (Int-5b) was prepared in analogy to Int-5a, by replacing Int-1a with Int-3a. MS [M+H]+: 270.1. Intermediate 5c 7-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxamide 7-(2-fluoro-4-hydroxy-phenoxy)-1-methyl-indazole-5-carboxamide (Int-5c) was prepared in analogy to Int-5a, by replacing Int-1a with Int-1 h in step 1. MS [M+H]+: 302.1. Intermediate 5d 4-cyano-3-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzamide 4-cyano-3-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzamide (Int-5d) was prepared in analogy to Int-5a, by replacing Int-1a with Int-24a. MS [M+H]+: 400.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.23 (s, 1 H), 8.01 (d, J = 8.0Hz, 1 H), 7.67 - 7.73 (m, 2 H), 7.38 (t, J = 9.2Hz, 1 H), 7.22 (s, 1 H), 7.13 (dd, J = 12.4, 2.8Hz, 1 H), 6.89 (dt, J = 9.2, 1.2Hz, 1 H), 4.26 (dd, J = 8.8, 7.2Hz, 2 H), 4.06 (t, J = 6.0Hz, 2 H), 3.57 (dd, J = 8.8, 7.2Hz, 2 H), 3.31 (br s, 2 H), 1.97 (quin, J = 6.4Hz, 2 H). Intermediate 6a Methyl 7-[4-(2-bromoethoxy)phenoxy]-1-methyl-indazole-5-carboxylate Int-1a Int-6aTo a solution of 1,2-dibromoethane (1.5 g, 7.98 mmol) and Int-1a (100.0 mg, 0.34 mmol) in ACN (1 mL) was added K2CO3 (140.0 mg, 1.01 mmol). The mixture was stirred at 80 °C for 5 h, cooled to rt and diluted with water (20 mL). The mixture was extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum to give crude methyl 7-[4-(2-bromoethoxy)phenoxy]-1-methyl-indazole-5-carboxylate (40.0 mg) as brown oil. MS [M+H]+: 405.0. Intermediate 6b Methyl 5-[4-(3-chloropropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxylate Methyl 5-[4-(3-chloropropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxylate (Int-6b) was prepared in analogy to Int-6a, by replacing Int-1a with Int-3a, 1,2-dibromoethane with 1- chloro-3-iodopropane. MS [M+H]+: 361.1. Intermediate 6c 5-[4-(3-chloropropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-(3-chloropropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Int-6c) was prepared in analogy to Int-6a, by replacing Int-1a with Int-5b, 1,2-dibromoethane with 1- chloro-3-iodopropane. MS [M+H]+: 346.1. Intermediate 6d Methyl 6-[2-fluoro-4-[3-(4-tolylsulfonyloxy)propoxy]phenoxy]-1-methyl-indazole-5- carboxylateInt-1f Int-6dStep 1: methyl 6-[2-fluoro-4-(3-hydroxypropoxy)phenoxy]-1-methyl-indazole-5-carboxylate To a solution of Int-1f (2000 mg, 6.32 mmol) in DMA (20 mL) were added 3-bromo-1- propanol (1.76 g, 12.65 mmol) and potassium carbonate (2.62 g, 18.97 mmol). The mixture was stirred for 8 h at 80oC, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by column chromatography to give methyl 6-[2-fluoro-4-(3- hydroxypropoxy)phenoxy]-1-methyl-indazole-5-carboxylate (1900 mg). MS [M+H]+: 375.1. Step 2: methyl 6-[2-fluoro-4-[3-(p-tolylsulfonyloxy)propoxy]phenoxy]-1-methyl-indazole-5- carboxylate To a solution of methyl 6-[2-fluoro-4-(3-hydroxypropoxy)phenoxy]-1-methyl-indazole-5- carboxylate (2000 mg, 5.34 mmol) in dichloromethane (30 mL) were added tosyl chloride (1.53 g, 8.01 mmol) and triethylamine (1.62 g, 16.03 mmol). The mixture was stirred for 18 h at rt, diluted with brine and extracted with DCM. The organic layer was dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography to give methyl 6- [2-fluoro-4-[3-(p-tolylsulfonyloxy)propoxy]phenoxy]-1-methyl-indazole-5-carboxylate (1700 mg). MS [M+H]+: 529.1. Intermediate 6e 7-[4-(3-chloropropoxy)phenoxy]-1-methyl-indazole-5-carboxamide 7-[4-(3-chloropropoxy)phenoxy]-1-methyl-indazole-5-carboxamide (Int-6e) was prepared in analogy to Int-6a, by replacing Int-1a with Int-5a, 1,2-dibromoethane with 1-chloro-3- iodopropane. MS [M+H]+: 360.0. Intermediate 6f 7-[4-(3-chloropropoxy)-2-fluoro-phenoxy]-1-methyl-indazole-5-carboxamide 7-[4-(3-chloropropoxy)-2-fluoro-phenoxy]-1-methyl-indazole-5-carboxamide (Int-6f) was prepared in analogy to Int-6a, by replacing Int-1a with Int-5c, 1,2-dibromoethane with 1- chloro-3-iodopropane. MS [M+H]+: 378.1. Intermediate 6g Methyl 5-[4-(3-chloropropoxy)-2-fluoro-phenoxy]imidazo[1,5-a]pyridine-7-carboxylate Methyl 5-[4-(3-chloropropoxy)-2-fluoro-phenoxy]imidazo[1,5-a]pyridine-7-carboxylate (Int-6g) was prepared in analogy to Int-6a, by replacing Int-1a with Int-3c, 1,2-dibromoethane with 1-chloro-3-iodopropane. MS [M+H]+: 379.1. Intermediate 6h 6-[4-(2-bromoethoxy)phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-(2-bromoethoxy)phenoxy]-1-methyl-indazole-5-carboxamide (Int-6h) was prepared in analogy to Int-6a, by replacing Int-1a with Int-4a, 1,2-dibromoethane with 1-chloro-3- iodopropane. MS [M+H]+: 390.1. Intermediate 6i Methyl 7-[4-(3-chloropropoxy)phenoxy]-1-methyl-indazole-5-carboxylate Methyl 7-[4-(3-chloropropoxy)phenoxy]-1-methyl-indazole-5-carboxylate (Int-6i) was prepared in analogy to Int-6a, by replacing 1,2-dibromoethane with 1-chloro-3-iodopropane. MS [M+H]+: 375.2. Intermediate 6j 6-[4-(3-chloropropoxy)phenoxy]-1-cyclopropyl-indazole-5-carboxamide 6-[4-(3-chloropropoxy)phenoxy]-1-cyclopropyl-indazole-5-carboxamide (Int-6j) was prepared in analogy to Int-6a, by replacing Int-1a with Int-4c, 1,2-dibromoethane with 1- chloro-3-iodopropane. MS [M+H]+: 386.1. Intermediate 7a 2-tetrahydrofuran-3-yloxyethanol Step 1 Step 2 Int-7a Step 1: 3-(2-benzyloxyethoxy)tetrahydrofuran To a 100 mL three-necked flask were added tetrahydrofuran-3-ol (1.0 g, 11.35 mmol) and THF (30 mL). The flask was evacuated and backfilled with nitrogen for three times. The solution was cooled to 0 °C with an ice bath. NaH (2.1 g, 52.5 mmol) was added in portions under N2 (while keeping the inner temperature below 5 °C). The resulting mixture was stirred for 0.5 h at 0 °C to give a brown mixture. To the mixture was added dropwise a solution of 2- bromoethoxymethylbenzene (7.3 g, 34.08 mmol) in THF (1 mL). The mixture was heated to 60 °C and stirred for 11.5 h under N2. The mixture was cooled, quenched with ice water (30 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified by flash chromatography to give 3-(2- benzyloxyethoxy)tetrahydrofuran (2.2 g) as yellow oil.1H NMR (400 MHz, CHCl3-d) δ ppm 7.28 - 7.37 (m, 4 H), 4.58 (s, 2 H), 4.15 - 4.21 (m, 1 H), 3.78 - 3.96 (m, 4 H), 3.58 - 3.66 (m, 4 H), 1.97 - 2.04 (m, 2 H). Step 2: 2-tetrahydrofuran-3-yloxyethanol (Int-7a) To a 100 mL flask were added 3-(2-benzyloxyethoxy)tetrahydrofuran (2.1 g, 9.76 mmol) and methanol (25 mL). Then Pd / C (0.5 g, 10% loading) was added in one portion under N2. The suspension was degassed and purged with H2 three times. The resulting mixture was stirred at 20 °C for 1 h under H2 (15 psi) and filtered through a pad of Celite. The cake was washed with MeOH. The combined filtrate was concentrated in vacuum to give 2-tetrahydrofuran-3- yloxyethanol as yellow oil (0.96 g) which was used in the next step without further purification. MS [M+H]+: 133.0. Intermediate 7b 2-tetrahydropyran-4-yloxyethanol 2-tetrahydropyran-4-yloxyethanol (Int-7b) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with tetrahydropyran-4-ol in step 1. MS [M+H]+: 147.0. Intermediate 7d 3-tetrahydropyran-4-yloxypropan-1-ol 3-tetrahydropyran-4-yloxypropan-1-ol (Int-7d) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol and 2-bromoethoxymethylbenzene with tetrahydropyran-4-ol and 3-bromopropoxymethylbenzene in step 1. MS [M+H]+: 161.0. Intermediate 7e and Intermediate 7f 2-[rac-(3R,4R)-3-methyltetrahydropyran-4-yl]oxyethanol and 2-[rac-(3R,4S)-3- methyltetrahydropyran-4-yl]oxyethanol 2-[rac-(3R,4R)-3-methyltetrahydropyran-4-yl]oxyethanol and 2-[rac-(3R,4S)-3- methyltetrahydropyran-4-yl]oxyethanol (Int-7e and Int-7f) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with 2-methylcyclohexanol in step 1. MS [M+H]+: 161.1. Intermediate 7g 2-tetrahydropyran-3-yloxyethanol 2-tetrahydropyran-3-yloxyethanol (Int-7g) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with tetrahydropyran-3-ol in step 1. MS [M+H]+: 147.0. Intermediate 7h 2-(8-oxabicyclo[3.2.1]octan-3-yloxy) ethanol 2-(8-oxabicyclo[3.2.1]octan-3-yloxy) ethanol (Int-7h) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with 8-oxabicyclo[3.2.1]octan-3-ol in step 1. MS [M+H]+: 173.1. Intermediate 7i 2-(2-oxaspiro[3.3]heptan-6-yloxy) ethanol 2-(2-oxaspiro[3.3]heptan-6-yloxy) ethanol (Int-7i) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with 2-oxaspiro[3.3]heptan-6-ol in step 1. MS [M+H]+: 159.1. Intermediate 7j 2-(1, 1-dioxothian-4-yl) oxyethanol 2-(1, 1-dioxothian-4-yl) oxyethanol (Int-7j) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with 1, 1-dioxothian-4-ol in step 1. MS [M+H]+: 195.1. Intermediate 7k 2-(2-oxaspiro[3.5]nonan-7-yloxy) ethanol 2-(2-oxaspiro[3.5]nonan-7-yloxy) ethanol (Int-7k) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with 2-oxaspiro[3.5]nonan-7-ol in step 1. MS [M+H]+: 143.1. Intermediate 7l 2-(2-methyltetrahydropyran-4-yl) oxyethanol 2-(2-methyltetrahydropyran-4-yl) oxyethanol (Int-7k) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with 2-methyltetrahydropyran-4-ol in step 1. MS [M+H]+: 161.1. Intermediate 7m 3-tetrahydropyran-4-ylpropan-1-ol PPhStep 13Int-7mStep 1: 3-hydroxypropyl(triphenyl)phosphonium;bromide To a solution of triphenylphosphane (3 g, 11.44 mmol) in toluene (20 mL) was added 3- bromo-1-propanol (1.91 g, 13.73 mmol). The mixture was stirred for 36 h at 100oC, cooled to rt and filtered. The cake was washed with diethyl ether and dried in vacuum to give 3- hydroxypropyl(triphenyl)phosphonium;bromide (3.66 g). MS [M]+: 321.1. Step 2: 3-tetrahydropyran-4-ylidenepropan-1-ol To a suspension of the 3-hydroxypropyl(triphenyl)phosphonium bromide (3.61 g, 8.99 mmol) in anhydrous tetrahydrofuran (30 mL) was added dropwise 2 M n-butyllithium (7.34 g, 10.79 mL, 21.57 mmol) at 0 °C under nitrogen atmosphere. The solution was stirred for 1 hour, and tetrahydro-4H-pyran-4-one (600 mg, 5.99 mmol). After stirring overnight at rt, the mixture was quenched with sat. ammonium chloride and filtered. The filtrate was dried over Na2SO4and concentrated in vacuum. The residue was purified by column chromatography to give 3- tetrahydropyran-4-ylidenepropan-1-ol (600 mg). MS [M+H]+:143.1. Step 3: 3-tetrahydropyran-4-ylpropan-1-ol (Int-7m) To a solution of 3-tetrahydropyran-4-ylidenepropan-1-ol (300 mg, 2.11 mmol) in methanol (20 mL) was added Pd(OH)2 / C (60 mg). The mixture was stirred for 20 h at rt under hydrogen atmosphere (1 atm) and filtered through Celite. The filtrate was concentrated in vacuum to give 3-tetrahydropyran-4-ylpropan-1-ol (280 mg), which was used directly in the next step without further purification. MS [M+H]+:145.1. Intermediate 7n tert-butyl (1S,5R)-3-(2-hydroxyethoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate tert-butyl (1S,5R)-3-(2-hydroxyethoxy)-8-azabicyclo[3.2.1]octane-8-carboxylate (Int-7n) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with 3-exo-Hydroxy-8- azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester in step 1. MS [M+H]+: 272.2. Intermediate 7o 2-[(3R)-tetrahydrofuran-3-yl]oxyethanol 2-[(3R)-tetrahydrofuran-3-yl]oxyethanol (Int-7o) was prepared in analogy to Int-7a, by replacing tetrahydrofuran-3-ol with (3R)-tetrahydrofuran-3-ol in step 1. MS [M+H]+: 161.0. Intermediate 8a 2-tetrahydropyran-4-yloxyethyl 4-methylbenzenesulfonate Int-7b Int-8aTo a solution of tosyl chloride (3.5 g, 18.30 mmol) and 2-tetrahydropyran-4-yloxyethanol (Int-7b) (1.78 g, 12.20 mmol) in DCM (30 mL) was added TEA (3.7 g, 36.6 mmol). The mixture was stirred at 20 °C for 14 h and diluted with water (20 mL). The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to give 2- tetrahydropyran-4-yloxyethyl 4-methylbenzenesulfonate (3.05 g) as colorless oil. MS [M+Na]+: 323.1. Intermediate 8d 2-(2-oxopyrrolidin-1-yl)ethyl 4-methylbenzenesulfonate 2-(2-oxopyrrolidin-1-yl)ethyl 4-methylbenzenesulfonate (Int-8d) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 1-(2-hydroxyethyl)pyrrolidin-2- one in step 1. MS [M+H]+: 268.1. Intermediate 8e 2-(1,2,4-triazol-4-yl)ethyl 4-methylbenzenesulfonate 2-(1,2,4-triazol-4-yl)ethyl 4-methylbenzenesulfonate (Int-8e) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 2-(1,2,4-triazol-4-yl)ethanol in step 1. MS [M+H]+: 284.2. Intermediate 8f 3-(2-oxopyrrolidin-1-yl)propyl 4-methylbenzenesulfonate 3-(2-oxopyrrolidin-1-yl)propyl 4-methylbenzenesulfonate (Int-8f) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 1-(3-hydroxypropyl)pyrrolidin-2- one in step 1. MS [M+H]+: 298.0. Intermediate 8g 2-tetrahydrofuran-3-yloxyethyl 4-methylbenzenesulfonate 2-tetrahydrofuran-3-yloxyethyl 4-methylbenzenesulfonate (Int-8g) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 2-tetrahydrofuran-3-yloxyethanol in step 1. MS [M+H]+: 287.0. Intermediate 8i (3-methoxy-3-methyl-butyl) 4-methylbenzenesulfonate (3-methoxy-3-methyl-butyl) 4-methylbenzenesulfonate (Int-8i) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 3-methoxy-3-methyl-butan-1-ol in step 1. MS [M+Na]+: 295.0. Intermediate 8j 3-tetrahydropyran-4-yloxypropyl 4-methylbenzenesulfonate 3-tetrahydropyran-4-yloxypropyl 4-methylbenzenesulfonate (Int-8j) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with Int-7d in step 1. MS [M+Na]+: 337.0. Intermediate 8k and Intermediate 8l 2-[rac-(3S,4S)-3-methyltetrahydropyran-4-yl]oxyethyl 4-methylbenzenesulfonate and 2- [rac-(3R,4S)-3-methyltetrahydropyran-4-yl]oxyethyl 4-methylbenzenesulfonate 2-[rac-(3S,4S)-3-methyltetrahydropyran-4-yl]oxyethyl 4-methylbenzenesulfonate and 2- [rac-(3R,4S)-3-methyltetrahydropyran-4-yl]oxyethyl 4-methylbenzenesulfonate (Int-8k and Int- 8l) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with Int- 7e and Int-7f in step 1. MS [M+H]+: 315.2. Intermediate 8m 2-tetrahydropyran-3-yloxyethyl 4-methylbenzenesulfonate 2-tetrahydropyran-3-yloxyethyl 4-methylbenzenesulfonate (Int-8m) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with Int-7g in step 1. MS [M+Na]+: 301.0. Intermediate 8n 2-(8-oxabicyclo[3.2.1]octan-3-yloxy) ethyl 4-methylbenzenesulfonate 2-(8-oxabicyclo[3.2.1]octan-3-yloxy) ethyl 4-methylbenzenesulfonate (Int-8n) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 2-(8- oxabicyclo[3.2.1]octan-3-yloxy) ethanol in step 1. MS [M+Na]+: 349.1. Intermediate 8o 2-(2-oxaspiro[3.3]heptan-6-yloxy) ethyl 4-methylbenzenesulfonate 2-(2-oxaspiro[3.3]heptan-6-yloxy) ethyl 4-methylbenzenesulfonate (Int-8o) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 2-(2- oxaspiro[3.3]heptan-6-yloxy) ethanol in step 1. MS [M+Na]+: 335.1. Intermediate 8p 2-(1, 1-dioxothian-4-yl) oxyethyl 4-methylbenzenesulfonate 2-(1, 1-dioxothian-4-yl)oxyethyl 4-methylbenzenesulfonate (Int-8p) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 2-(1,1-dioxothian-4- yl)oxyethanol in step 1. MS [M+Na]+: 371.2. Intermediate 8q 2-(2-oxaspiro[3.5]nonan-7-yloxy) ethyl 4-methylbenzenesulfonate 2-(2-oxaspiro[3.5]nonan-7-yloxy) ethyl 4-methylbenzenesulfonate (Int-8q) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 2-(2-oxaspiro[3.5]nonan- 7-yloxy) ethanol in step 1. MS [M+Na]+: 363.1. Intermediate 8r 2-(2-methyltetrahydropyran-4-yl)oxyethyl 4-methylbenzenesulfonate 2-(2-methyltetrahydropyran-4-yl)oxyethyl 4-methylbenzenesulfonate (Int-8r) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 2-(2- methyltetrahydropyran-4-yl)oxyethanol in step 1. MS [M+Na]+: 337.1. Intermediate 8s 3-tetrahydropyran-4-ylpropyl 4-methylbenzenesulfonate 3-tetrahydropyran-4-ylpropyl 4-methylbenzenesulfonate (Int-8s) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with 3-tetrahydropyran-4-ylpropan-1- ol (Int-7m) in step 1. MS [M+H]+: 299.1. Intermediate 8t tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate tert-butyl 4-(2-hydroxyethyl)piperidine-1-carboxylate (Int-8t) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with tert-butyl 4-(2- hydroxyethoxy)piperidine-1-carboxylate in step 1. MS [M+H]+: 400.2.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.81 (d, J = 8.4Hz, 2 H), 7.35 (d, J = 8.0Hz, 2 H), 4.16 (dd, J = 5.2, 4.4Hz, 2 H), 3.58 - 3.71 (m, 4 H), 3.44 (dt, J = 7.6, 4.0Hz, 1 H), 3.02 - 3.15 (m, 2 H), 2.46 (s, 3 H), 1.73 (ddt, J = 9.2, 6.0, 3.2, 3.2Hz, 2 H), 1.39 - 1.51 (m, 11 H). Intermediate 8u tert-butyl 3-(2-hydroxyethyl)pyrrolidine-1-carboxylate tert-butyl 3-(2-hydroxyethyl)pyrrolidine-1-carboxylate (Int-8u) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with tert-butyl 3-(2- hydroxyethoxy)pyrrolidine-1-carboxylatein step 1. MS [M-Boc+H]+: 286.1 [M-Boc+H]+.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.80 (d, J = 8.4Hz, 2 H), 7.35 (d, J = 8.4Hz, 2 H), 4.15 (t, J = 4.8Hz, 2 H), 4.00 (br s, 1 H), 3.63 (br s, 2 H), 3.49 - 3.27 (m, 4 H), 2.46 (s, 3 H), 1.97 - 1.84 (m, 2 H), 1.47 (s, 9 H). Intermediate 8v tert-butyl (1R,5S)-3-[2-(p-tolylsulfonyloxy)ethoxy]-8-azabicyclo[3.2.1]octane-8-carboxylate tert-butyl (1R,5S)-3-[2-(p-tolylsulfonyloxy)ethoxy]-8-azabicyclo[3.2.1]octane-8- carboxylate (Int-8v) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4- yloxyethanol with Int-7n in step 1. MS [M+Na]+: 426.4. Intermediate 8w 2-[(3R)-tetrahydrofuran-3-yl]oxyethanol 2-[(3R)-tetrahydrofuran-3-yl]oxyethanol (Int-8w) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with Int-7o in step 1.1H NMR (400 MHz, DMSO- d6) δ ppm 7.78 (d, J = 8.4Hz, 2 H), 7.48 (d, J = 8.0Hz, 2 H), 4.11 (t, J = 4.4Hz, 2 H), 4.04 (td, J = 4.0, 2.4Hz, 1 H), 3.68 - 3.6 (m, 2 H), 3.60 - 3.49 (m, 4 H), 2.42 (s, 3 H), 1.93 - 1.79 (m, 1 H), 1.77 - 1.63 (m, 1 H). Intermediate 8x oxetan-3-ylmethyl 4-methylbenzenesulfonate oxetan-3-ylmethyl 4-methylbenzenesulfonate (Int-8x) was prepared in analogy to Int-8a, by replacing 2-tetrahydropyran-4-yloxyethanol with oxetan-3-ylmethanol in step 1. MS [M+H]+: 265.1. Intermediate 9a 4-(2-tetrahydropyran-4-yloxyethoxy)phenol Step 1: 4-[2-(4-benzyloxyphenoxy)ethoxy]tetrahydropyran To a solution of 2-tetrahydropyran-4-yloxyethyl 4-methylbenzenesulfonate (2.6 g, 8.80 mmol) and 4-benzyloxyphenol (1.6 g, 8.00 mmol) in DMF (30 mL) was added K2CO3 (2.2 g, 16.0 mmol). The mixture was stirred at 80 °C for 18 h, cooled to rt and filtered through a pad of Celite. The cake was washed with DCM. The combined filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give 4-[2-(4- benzyloxyphenoxy)ethoxy]tetrahydropyran (1.76 g) as yellow oil. MS [M+H]+: 329.1. Step 2: 4-(2-tetrahydropyran-4-yloxyethoxy)phenol (Int-9a) To a 100 mL flask were added 4-[2-(4-benzyloxyphenoxy)ethoxy]tetrahydropyran (1.76 g, 5.36 mmol), methanol (30 mL) and Pd / C (352 mg, 10% loading). The mixture was degassed and purged with H2three times. After stirring at 20 °C for 14 h under H2ballon, the mixture was filtered through a pad of Celite. The cake was washed with methanol. The filtrate was concentrated in vacuum to give crude 4-(2-tetrahydropyran-4-yloxyethoxy)phenol (1.24 g) which was used in the next step without further purification. MS [M+H]+:239.0. Intermediate 9b 2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenol 2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenol (Int-9b) was prepared in analogy to Int-9a, by replacing 4-benzyloxyphenol with 4-benzyloxy-3-fluoro-phenol in step 1. MS [M+H]+:257.0. Intermediate 9c 2,6-difluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenol 2,6-difluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenol (Int-9c) was prepared in analogy to Int-9a, by replacing 4-benzyloxyphenol with 4-benzyloxy-3,5-difluoro-phenol in step 1. MS [M+H]+:275.0. Intermediate 9d 2-methyl-4-(2-tetrahydropyran-4-yloxyethoxy)phenol 2-methyl-4-(2-tetrahydropyran-4-yloxyethoxy)phenol (Int-9d) was prepared in analogy to Int-9a, by replacing 4-benzyloxyphenol with 4-benzyloxy-3-methyl-phenol in step 1. MS [M+H]+:253.0. Intermediate 9e 2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenol 2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenol (Int-9e) was prepared in analogy to Int-9a, by replacing 4-benzyloxyphenol with 4-benzyloxy-3-chloro-phenol in step 1; Pd / C- methanol with neat TFA in step 2. MS [M+H]+:273.0. Intermediate 10a 3-(2-benzyloxyethoxy)azetidine Step 1 Step 1: tert-butyl 3-(2-benzyloxyethoxy)azetidine-1-carboxylate To a solution of tert-butyl 3-hydroxyazetidine-1-carboxylate (5.0 g, 28.87 mmol) in THF (70 mL) was added NaH (1.7 g, 43.3 mmol) at 0 °C. The mixture was stirred 0.5 h under nitrogen atmosphere. A solution of benzyl 2-bromoethyl ether (6.2 g, 28.87 mmol) in THF (20 mL) was added to the mixture at 0 °C. The reaction was warm to 60 °C and stirred for 12 h. The mixture was cooled to rt and quenched with water (100 mL). The aqueous phase was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to give tert-butyl 3-(2-benzyloxyethoxy)azetidine-1-carboxylate (7.0 g) as yellow oil. MS [M-Boc+H]+: 208.1. Step 2: 3-(2-benzyloxyethoxy)azetidine (Int-10a) To a solution of tert-butyl 3-(2-benzyloxyethoxy)azetidine-1-carboxylate (7.0 g, 22.77 mmol) in DCM (70 mL) was added TFA (20.0 mL, 22.77 mmol). The solution was stirred at 20 °C for 12 h and concentrated in vacuum. The residue was purified by reversed-phase chromatography to give 3-(2-benzyloxyethoxy)azetidine (2.0 g) as light yellow oil. MS [M+H]+: 208.1.1H NMR (400 MHz, DMSO-d6) δ ppm 7.49 - 7.21 (m, 5H), 4.49 (s, 2H), 4.42 - 4.34 (m, 1H), 4.10 (br s, 2H), 3.82 (br s, 2H), 3.65 - 3.48 (m, 4H). Intermediate 14a 1-(2-chloroethyl)-3-methyl-imidazolidin-2-one Int-14aStep 1: 1-(2-chloroethyl)imidazolidin-2-one To a solution of 1-(2-hydroxyethyl)imidazolidin-2-one (2.0 g, 15.37 mmol) in chloroform (2.5 mL) was added SOCl2(2.3 mL, 30.73 mmol). The solution was stirred at 50 °C for 3 h and concentrated in vacuum to give 1-(2-chloroethyl)imidazolidin-2-one (1.9 g) as yellow oil.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.96 (br s, 1 H), 3.65 - 3.58 (m, 4 H), 3.55 - 3.48 (m, 4 H). Step 2: 1-(2-chloroethyl)-3-methyl-imidazolidin-2-one (Int-14a) To a mixture of 1-(2-chloroethyl)imidazolidin-2-one (1.0 g, 6.73 mmol) in THF (10 mL) was added NaH (465.0 mg, 11.63 mmol) in portions over 0.2 h at 0 °C. Iodomethane (1.9 g, 13.46 mmol) was added. The resulting mixture was stirred at 25 °C for 12 h and quenched with water (20 mL). The mixture was extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to give 1-(2-chloroethyl)-3-methyl-imidazolidin-2-one (120.0 mg) as yellow liquid. MS [M+H]+: 163.1. Intermediate 16a Methyl 2-(aminomethyl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine-4- carboxylate Step 1: methyl 2-cyano-5-fluoro-pyridine-4-carboxylate Methyl 2-bromo-5-fluoro-pyridine-4-carboxylate (3.5 g, 15.00 mmol) was dissolved in DMF (70 mL). To this solution was added copper (I) cyanide (6.7 g, 75 mmol) in one portion. The mixture was degassed and backfilled with N2 and stirred at 120 °C for 12 h under N2. The resulting mixture was cooled to rt, poured into water and extracted with ethyl acetate. The combined organic layer was washed with brine and concentrated in vacuum. The residue was purified by column chromatography to give methyl 2-cyano-5-fluoro-pyridine-4-carboxylate (1.6 g) as light yellow solid. MS [M+H]+: 180.9. Step 2: methyl 2-cyano-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine-4- carboxylate To a mixture of methyl 2-cyano-5-fluoro-pyridine-4-carboxylate (1.6 g, 8.79 mmol) and Int-9a (2.1 g, 8.79 mmol) in DMF (30 mL) was added K2CO3(2.4 g, 17.57 mmol). The mixture was stirred at 100 °C for 12 h, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by column chromatography to give methyl 2-cyano-5-[4-(2- tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine-4-carboxylate (3.5 g) as light yellow solid. MS [M+H]+: 399.3. Step 3: methyl 2-[(tert-butoxycarbonylamino)methyl]-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]pyridine-4-carboxylate To a mixture of methyl 2-cyano-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine- 4-carboxylate (850.0 mg, 2.31 mmol) and Boc2O (1.9 g, 8.53 mmol) in methanol (30 mL) was added Pd / C (170 mg, 10% loading). The mixture was degassed and purged with H2 three times, stirred at 20 °C for 14 h under H2 ballon and filtered through a Celite pad. The filtrate was concentrated in vacuum. The residue was purified by column chromatography to give methyl 2- [(tert-butoxycarbonylamino)methyl]-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine- 4-carboxylate (860 mg) as yellow oil. MS [M+H]+: 503.5. Step 4: methyl 2-(aminomethyl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine- 4-carboxylate (Int-16a) To a 100 mL round-bottom flask were added methyl 2-[(tert- butoxycarbonylamino)methyl]-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine-4- carboxylate (1.02 g, 2.03 mmol), DCM (20 mL) and 4 M HCl(g)in dioxane (3.5 mL). The mixture was stirred at 20 °C for 14 h, quenched with sat. NaHCO3 and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The crude methyl 2-(aminomethyl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine-4- carboxylate (788.0 mg) was used in the next step without further purification. MS [M+H]+: 403.5. Intermediate 17a 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxylic acid Step 1: methyl 2-(formamidomethyl)-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]pyridine-4-carboxylate To an 8 mL vial were added Int-16a (402.4 mg, 1.00 mmol) and ethyl formate (1 mL). The mixture was stirred at 60 °C for 2 h, cooled to rt and concentrated in vacuum. The crude methyl 2-(formamidomethyl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyridine-4-carboxylate (421.1 mg) was used in the next step without further purification. MS [M+H]+: 431.0. Step 2: methyl 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxylate To a solution of methyl 2-(formamidomethyl)-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]pyridine-4-carboxylate (430.0 mg, 1.00 mmol) in dry toluene (10 mL) was added POCl3 (184.0 mg, 1.20 mmol) at 0 °C. The resulting solution was stirred at 100 °C for 1 h, cooled to rt and quenched with sat. NaHCO3at 0 °C. The mixture was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified by column chromatography to give methyl 3-methyl-6-[4-(2- tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxylate (380.0 mg) as brown oil. MS [M+H]+: 413.4. Step 3: 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxylic acid (Int-17a) To a 50 mL round-bottom flask were added methyl 3-methyl-6-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxylate (380.5 mg, 0.92 mmol) and methanol (8 mL). LiOH•H2O (78.0 mg, 1.85 mmol) and water (1.6 mL) were added. The mixture was stirred at 50 °C for 2 h, cooled to rt and adjusted to pH = 5~7 with 1M HCl aqueous solution. The mixture was extracted with DCM. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum to give Int-17a (237.0 mg) which was used directly in the next step. MS [M+H]+: 399.2. Intermediate 19a 1-(3-bromopropyl)-5-methyl-pyrrolidin-2-one To a solution of 5-methylpyrrolidin-2-one (0.99 g, 10.00 mmol) in THF (10 mL) was added NaH (600.0 mg, 15.00 mmol) in portions at 0 °C. The suspension was stirred at 0 °C for 0.5 h. 1,3-dibromopropane (10.1 g, 50.00 mmol) was added. The resulting mixture was stirred at 25 °C for another 2 h, quenched with sat. NH4Cl and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified by flash chromatography to give 1-(3-bromopropyl)-5-methyl-pyrrolidin-2-one (928.2 mg) as yellow liquid. MS [M+H]+: 219.9. Intermediate 20a (2-methyl-3-tetrahydropyran-4-yloxy-propyl) 4-methylbenzenesulfonate Int-20a Step 1: methyl 2-(tetrahydropyran-4-yloxymethyl)prop-2-enoate To a mixture of tetrahydropyran-4-ol (2.0 g, 19.60 mmol) in THF (40 mL) was added NaH (1.2 g, 29.40 mmol) in portions at 0 °C. The mixture was stirred at 0 °C for 0.5 h. Methyl 2- (bromomethyl)prop-2-enoate (4.2 g, 23.50 mmol) was added. The resulting mixture was stirred at 25 °C for another 2 h, quenched with sat. NH4Cl and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to give methyl 2-(tetrahydropyran-4- yloxymethyl)prop-2-enoate (3.4 g) as yellow liquid. MS [M+H]+: 201.0. Step 2: methyl 2-methyl-3-tetrahydropyran-4-yloxy-propanoate To a 100 mL flask were added methyl 2-(tetrahydropyran-4-yloxymethyl)prop-2-enoate (3.4 g, 17.0 mmol) and methanol (30 mL). Pd / C (0.7 g, 10% loading) was added in one portion under N2. The suspension was degassed and purged with H2 three times. The resulting mixture was stirred at 20 °C for 12 h under H2 balloon and filtered through a pad of Celite. The cake was washed with MeOH. The combined filtrate was concentrated in vacuum to give methyl 2- methyl-3-tetrahydropyran-4-yloxy-propanoate as yellow oil (3.2 g) which was used in the next step without further purification. MS [M+H]+: 203.0. Step 3: 2-methyl-3-tetrahydropyran-4-yloxy-propan-1-ol To a solution of methyl 2-methyl-3-tetrahydropyran-4-yloxy-propanoate (3.0 g, 14.70 mmol) in THF (40 mL) was added LiAlH4 (835.0 mg, 22.0 mmol) in portions at 0 °C. The mixture was stirred at rt for 1 h and quenched successively with 0.84 mL H2O, 0.84 mL 10% NaOH(aq.)and 2.52 mL H2O at 0 °C. The resulting mixture was filtered through a pad of Celite. The cake was washed with DCM. The combined filtrate was concentrated in vacuum to give 2- methyl-3-tetrahydropyran-4-yloxy-propan-1-ol as yellow oil (2.1 g) which was used in the next step without further purification. MS [M+H]+: 175.1. Step 4: (2-methyl-3-tetrahydropyran-4-yloxy-propyl) 4-methylbenzenesulfonate (Int-20a) To a solution of tosyl chloride (4.0 g, 21.00 mmol) and 2-methyl-3-tetrahydropyran-4- yloxy-propan-1-ol (2.4 g, 12.20 mmol) in DCM (30 mL) was added TEA (4.3 g, 42.00 mmol). The mixture was stirred at 20 °C for 14 h and diluted with water (20 mL). The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to (2-methyl-3- tetrahydropyran-4-yloxy-propyl) 4-methylbenzenesulfonate (4.71 g) as colorless oil. MS [M+H]+: 329.2. Intermediate 21a 1-[3-(3-fluoro-4-hydroxy-phenoxy)propyl]pyrrolidin-2-one Step 3 Step 4 Step 1: 3-(4-benzyloxy-3-fluoro-phenoxy)propan-1-ol To a mixture of 4-benzyloxy-3-fluoro-phenol (4.0 g, 18.33 mmol) and K2CO3 (7.6 g, 54.99 mmol) in DMF (60 mL) was added 3-bromopropan-1-ol (5.1 g, 36.66 mmol). The reaction was stirred at 80 °C for 16 h, cooled to rt, diluted with water (30 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to give 3-(4-benzyloxy-3-fluoro-phenoxy)propan- 1-ol (5.4 g) as yellow solid. MS [M+H]+: 277.1. Step 2: 3-(4-benzyloxy-3-fluoro-phenoxy)propyl 4-methylbenzenesulfonate To a solution of tosyl chloride (4.6 g, 24.20 mmol) and 3-(4-benzyloxy-3-fluoro- phenoxy)propan-1-ol (4.5 g, 16.10 mmol) in DCM (50 mL) was added TEA (4.9 g, 48.30 mmol). The mixture was stirred at 20 °C for 14 h and diluted with water (20 mL). The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to give 3-(4-benzyloxy-3-fluoro-phenoxy)propyl 4-methylbenzenesulfonate (3.89 g) as white solid. MS [M+Na]+: 453.2. Step 3: 1-[3-(4-benzyloxy-3-fluoro-phenoxy)propyl]pyrrolidin-2-one To a mixture of pyrrolidin-2-one (427.0 mg, 5.02 mmol) in DMF (20 mL) was added NaH (268.0 mg, 6.70 mmol) in portions at 0 °C. The mixture was stirred at 0 °C for 0.5 h.3-(4- benzyloxy-3-fluoro-phenoxy)propyl 4-methylbenzenesulfonate (1.2 g, 2.79 mmol) was added. The resulting mixture was stirred at 25 °C for 12 h, quenched with sat. NH4Cl and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified by flash chromatography to give 1-[3-(4-benzyloxy-3- fluoro-phenoxy)propyl]pyrrolidin-2-one (1.4 g) as yellow liquid. MS [M+H]+: 344.4. Step 4: 1-[3-(3-fluoro-4-hydroxy-phenoxy)propyl]pyrrolidin-2-one (Int-21a) To a 100 mL flask were added 1-[3-(4-benzyloxy-3-fluoro-phenoxy)propyl]pyrrolidin-2- one (1.4 g, 4.10 mmol) and methanol (30 mL). Pd / C (280.0 mg, 10% loading) was added in one portion. The suspension was degassed and purged with H2three times. The resulting mixture was stirred at 20 °C for 12 h under H2balloon and filtered through a pad of Celite. The cake was washed with MeOH. The combined filtrate was concentrated in vacuum to give 1-[3-(3-fluoro-4- hydroxy-phenoxy)propyl]pyrrolidin-2-one as yellow oil (960 mg) which was used in the next step without further purification. MS [M+H]+: 254.1. Intermediate 21b 3-[3-(3-fluoro-4-hydroxy-phenoxy)propyl]oxazolidin-2-one 3-[3-(3-fluoro-4-hydroxy-phenoxy)propyl]oxazolidin-2-one was prepared in analogy to Int- 21a, by replacing pyrrolidin-2-one with oxazolidin-2-one in step 3. MS [M+H]+:256.1. Intermediate 21c 3-[3-(4-hydroxyphenoxy)propyl]oxazolidin-2-one Int-21c Step 1: 1-benzyloxy-4-(3-bromopropoxy)benzene To a mixture of 4-benzyloxyphenol (1.5 g, 7.50 mmol) and K2CO3(3.1 g, 22.50 mmol) in MeCN (40 mL) was added 1,3-dibromopropane (9.1 g, 45.00 mmol). The reaction was stirred at 80 °C for 16 h, cooled to rt and filtered through a Celite pad. The filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give 1-benzyloxy-4-(3- bromopropoxy)benzene (2.0 g) as yellow solid. MS [M+Na]+: 323.0. Step 2: 3-[3-(4-benzyloxyphenoxy)propyl]oxazolidin-2-one To a mixture of oxazolidin-2-one (493.0 mg, 5.66 mmol) in DMF (30 mL) was added NaH (340.0 mg, 8.50 mmol) in portions at 0 °C. The mixture was stirred at 0 °C for 0.5 h.1- benzyloxy-4-(3-bromopropoxy)benzene (2.0 g, 6.23 mmol) was added. The resulting mixture was stirred at 25 °C for 2 h, quenched with sat. NH4Cl and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified by flash chromatography to give 3-[3-(4- benzyloxyphenoxy)propyl]oxazolidin-2-one (1.7 g) as yellow liquid. MS [M+H]+: 328.2. Step 3: 3-[3-(4-hydroxyphenoxy)propyl]oxazolidin-2-one (Int-21c) To a 100 mL flask were added 3-[3-(4-benzyloxyphenoxy)propyl]oxazolidin-2-one (1.7 g, 5.20 mmol) and methanol (30 mL). Pd / C (340.0 mg, 10% loading) was added in one portion. The suspension was degassed and purged with H2 three times. The resulting mixture was stirred at 20 °C for 12 h under H2balloon and filtered through a pad of Celite. The cake was washed with MeOH. The combined filtrate was concentrated in vacuum to give 3-[3-(4- hydroxyphenoxy)propyl]oxazolidin-2-one as yellow oil (1.14 g) which was used in the next step without further purification. MS [M+H]+: 238.0. Intermediate 21d 4-[3-(3-fluoro-4-hydroxy-phenoxy)propyl]morpholin-3-one 4-[3-(3-fluoro-4-hydroxy-phenoxy)propyl]morpholin-3-one was prepared in analogy to Int- 21a, by replacing pyrrolidin-2-one with morpholin-3-one in step 3. MS [M+H]+: 270.0. Intermediate 21e 2-fluoro-4-[3-(4-methylpiperazin-1-yl)propoxy]phenol 4-[3-(3-fluoro-4-hydroxy-phenoxy)propyl]morpholin-3-one was prepared in analogy to Int- 21c, by replacing 1,3-dibromopropane with 1-chloro-3-iodo-propane in step 1, pyrrolidin-2-one with 1-methylpiperazine in step 3. MS [M+H]+: 269.2. Intermediate 22a 3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]propanoic acid Int-4a Int-22aStep 1: benzyl (E)-3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]prop-2-enoate To a solution of Int-4a (650.0 mg, 2.30 mmol) and DMAP (281.0 g, 2.30 mmol) in DCM (30 mL) was added benzyl prop-2-ynoate (442.0 mg, 2.76 mmol) at 0 °C. The mixture was stirred at 20 °C for 1 h and concentrated in vacuum. The residue was purified by flash chromatography to give benzyl (E)-3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]prop- 2-enoate (842.1 mg) as brown solid. MS [M+Na]+: 444.1. Step 2: 3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]propanoic acid (Int-22a) To a 250 mL flask were added benzyl (E)-3-[4-(5-carbamoyl-1-methyl-indazol-6- yl)oxyphenoxy]prop-2-enoate (800 mg, 1.80 mmol) and methanol (150 mL). Pd / C (400 mg, 10% loading) was added in one portion. The suspension was degassed and purged with H2three times. The resulting mixture was stirred at 20 °C for 12 h under H2balloon and filtered through a pad of Celite. The cake was washed with MeOH. The combined filtrate was concentrated in vacuum to give 3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]propanoic acid (560 mg) which was used in the next step without further purification. MS [M+H]+: 356.1. Intermediate 22b 3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxy-3-fluoro-phenoxy]propanoic acid 3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxy-3-fluoro-phenoxy]propanoic acid (Int-22b) was prepared in analogy to Int-22a, by replacing Int-4a with Int-4b in step 1. MS [M+H]+: 374.1. Intermediate 22c 3-[4-(5-carbamoyl-1-methyl-indazol-7-yl)oxyphenoxy]propanoic acid 3-[4-(5-carbamoyl-1-methyl-indazol-7-yl)oxyphenoxy]propanoic acid (Int-22c) was prepared in analogy to Int-22a, by replacing Int-4a with Int-5a in step 1. MS [M+H]+: 356.1. Intermediate 22d 3-[4-(5-carbamoyl-1-methyl-indazol-7-yl)oxy-3-fluoro-phenoxy]propanoic acid 3-[4-(5-carbamoyl-1-methyl-indazol-7-yl)oxy-3-fluoro-phenoxy]propanoic acid (Int-22d) was prepared in analogy to Int-22a, by replacing Int-4a with Int-5c in step 1. MS [M+H]+: 374.1. Intermediate 23a 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropyl)phenoxy]indazole-5-carboxylic acid Step 1: methyl 6-[4-(3-hydroxypropyl)phenoxy]-1-methyl-indazole-5-carboxylate To a solution of 6-bromo-1-methyl-indazole-5-carboxylic acid methyl ester (500 mg, 1.86 mmol) in dimethyl sulfoxide (3 mL) were added 4-(3-hydroxypropyl)phenol (424.18 mg, 2.79 mmol), potassium phosphate (788.84 mg, 3.72 mmol), BMPPO (64. mg, 185.81 μmol) and cuprous iodide (35.39 mg, 185.81 μmol). The mixture was stirred for 18 h at 120oC under nitrogen atmosphere and cooled to rt. The mixture was diluted with brine and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography to give methyl 6-[4-(3-hydroxypropyl)phenoxy]-1-methyl- indazole-5-carboxylate (270 mg). MS [M+H]+: 341.1. Step 2: methyl 1-methyl-6-[4-[3-(p-tolylsulfonyloxy)propyl]phenoxy]indazole-5-carboxylate To a solution of methyl 6-[4-(3-hydroxypropyl)phenoxy]-1-methyl-indazole-5-carboxylate (270 mg, 0.79 mmol) in dichloromethane (6 mL) were added tosyl chloride (226.85 mg, 1.19 mmol,) and triethylamine (240.81 mg, 2.38 mmol). The mixture was stirred for 18 h at rt, diluted with brine and extracted with DCM. The organic layer was dried over Na2SO4and concentrated in vacuum. The residue was purified by column chromatography to give methyl 1-methyl-6-[4- [3-(p-tolylsulfonyloxy)propyl]phenoxy]indazole-5-carboxylate (230 mg). MS [M+H]+: 495.2. Step 3: 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropyl)phenoxy]indazole-5-carboxylic acid (Int-23a) To a solution of tetrahydropyran-4-ol (30.98 mg, 0.30 mmol) in DMF (5 mL) was added sodium hydride (32.35 mg, 0.81 mmol) at 0oC. The mixture was stirred for 30 min. Methyl 1- methyl-6-[4-[3-(p-tolylsulfonyloxy)propyl]phenoxy]indazole-5-carboxylate (100 mg, 0.20 mmol) was added. The reaction was stirred for 16 h at rt, quenched with aq. ammonia chloride and acidified with 6 N HCl. The mixture was diluted with brine and extracted with EtOAc. The organic layer was dried over Na2SO4and concentrated in vacuum. The residue was used directly in the next step without further purification. MS [M+H]+: 411.2. Intermediate 24a Methyl 4-cyano-3-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzoate Step 1: methyl 4-cyano-3-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzoate (Int-24a) To a 40 mL flask were added Int-21b (350.0 mg, 1.37 mmol) and ACN (4 mL). Then methyl 4-cyano-3-fluoro-benzoate (245.7 mg, 1.37 mmol) and K2CO3 (568.6 mg, 4.11 mmol) were added. The mixture was stirred at 50 °C for 16 h, cooled to rt and concentrated in vacuum. The residue was purified by reversed-phase chromatography to give methyl 4-cyano-3-[2-fluoro- 4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzoate (340.0 mg) as brown solid. MS [M+H]+: 415.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.08 (d, J = 8.0Hz, 1 H), 7.77 (dd, J = 8.0, 1.6Hz, 1 H), 7.43 (t, J = 9.2Hz, 1 H), 7.18 (s, 1 H), 7.15 (dd, J = 12.4, 2.8Hz, 1 H), 6.92 (dt, J = 9.2, 1.6Hz, 1 H), 4.26 (dd, J = 8.8, 7.4Hz, 2 H), 4.07 (t, J = 6.0Hz, 2 H), 3.82 (s, 3 H) 3.57 (dd, J = 8.8, 7.2Hz, 2 H), 3.34 (br s, 2 H), 1.97 (t, J = 6.8Hz, 2 H). Intermediate 24b Methyl 4-cyano-5-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-2-methyl- benzoate Methyl 4-cyano-5-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-2-methyl- benzoate (Int-24b) was prepared in analogy to Int-24a, by replacing methyl 4-cyano-3-fluoro- benzoate with methyl 4-cyano-5-fluoro-2-methyl-benzoate in step 1. Yellow solid, MS [M+H]+: 429.1.1H NMR (400 MHz, DMSO-d6) δ ppm 7.92 (s, 1 H), 7.37 (t, J = 9.2Hz, 1 H), 7.12 (dd, J = 12.4, 2.8Hz, 1 H), 7.09 (s, 1 H), 6.88 (ddd, J = 9.2, 2.8, 1.2Hz, 1 H), 4.26 (dd, J = 8.8, 7.2Hz, 2 H), 4.05 (t, J = 6.0Hz, 2 H), 3.77 (s, 3 H), 3.57 (dd, J = 8.8, 7.2Hz, 2 H), 3.31 (br s, 2 H), 2.45 (s, 3 H), 1.96 (t, J = 6.4Hz, 2 H). Intermediate 24c 4-bromo-2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzonitrile 4-bromo-2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzonitrile (Int-24c) was prepared in analogy to Int-24a, by replacing methyl 4-cyano-3-fluoro-benzoate with methyl 4-cyano-5-fluoro-2-methyl-benzoate in step 1. Grey solid, MS [M+H]+: 435.0. Intermediate 26 2-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]acetic acid Step 1: tert-butyl 2-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]acetate A mixture of tert-butyl 2-bromoacetate (2.58 g, 1.96 mL, 13.24 mmol), Int-4a (2500 mg, 8.83 mmol) and K2CO3(3.66 g, 26.48 mmol) in acetone (25 mL) was heated at 60 °C for 4 h and cooled to rt. The mixture was filtered and the filtration was concentrated in vacuum. The residue was dissolved in DCM. The solution was washed with water, dried over Na2SO4 and concentrated in vacuum to give the crude product tert-butyl 2-[4-(5-carbamoyl-1-methyl- indazol-6-yl)oxyphenoxy]acetate (3 g). MS [M+Na]: 420.1. Step 2: 2-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]acetic acid (Int-26) To a solution of tert-butyl 2-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]acetate (3 g, 7.55 mmol) in DCM (30 mL) was added TFA (10 mL). The solution was stirred for 3 hr at rt and concentrated in vacuum to give the crude product 2-[4-(5-carbamoyl-1-methyl-indazol-6- yl)oxyphenoxy]acetic acid as brown solid. MS [M+H]+: 342.1. Intermediate 27a 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide Step 1: methyl 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxylate To a solution of Int-3a (600 mg, 2.11 mmol ) in N,N-dimethylformamide (10 mL) were added Int-8a (950.97 mg, 3.17 mmol) and potsssium carbonate (583.43 mg, 4.22 mmol), the reaction was stirred for 16 h at 100oC, cooled to rt and fitered. The filtrate was concentrated in vacuum and the residue was purified by column chromatography to give methyl 5-[4-(2- tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxylate (720 mg). MS [M+H]+: 413.2. Step 2: 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carbohydrazide (Int-27a) To a solution of methyl 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5- a]pyridine-7-carboxylate (720 mg, 1.75 mmol) in methanol (10 mL) was added hydrazine hydrate (3.5 g, 69.83 mmol). The reaction was stirred for 15 h at 80oC, cooled to rt and concentrated in vacuum to give 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5- a]pyridine-7-carbohydrazide (Int-27a) (720 mg). MS [M+H]+: 413.2. Intermediate 27b 5-[4-(3-hydroxypropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide 5-[4-(3-hydroxypropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide (Int-27b) was prepared in analogy to Int-27a, by replacing Int-8a with 3-bromopropan-1-ol in step 1. MS [M+H]+: 343.1. Intermediate 27c 5-[4-(3-hydroxy-3-methyl-butoxy)phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide 5-[4-(3-hydroxy-3-methyl-butoxy)phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide (Int- 27c) was prepared in analogy to Int-27a, by replacing Int-8a with 4-bromo-2-methyl-butan-2-ol in step 1. MS [M+H]+: 371.2. Intermediate 27d 5-[4-(3-methylsulfonylpropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide 5-[4-(3-methylsulfonylpropoxy)phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide(Int- 27d) was prepared in analogy to Int-27a, by replacing Int-8a with 1-bromo-3-methylsulfonyl- propane in step 1. MS [M+H]+: 405.1. Intermediate 27e 5-[4-[2-(2-hydroxyethoxy)ethoxy]phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide 5-[4-[2-(2-hydroxyethoxy)ethoxy]phenoxy]imidazo[1,5-a]pyridine-7-carbohydrazide (Int- 27e) was prepared in analogy to Int-27a, by replacing Int-8a with 2-(2-bromoethoxy)ethanol in step 1. MS [M+H]+: 373.1. Intermediate 27f 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carbohydrazide 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carbohydrazide (Int- 27f) was prepared in analogy to Int-27a, by replacing Int-3a with Int-1a in step 1. MS [M+H]+: 427.2. Intermediate 28 4-[6-(4-methyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenol Int-28 Step 1: 8-(4-benzyloxyphenoxy)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,5- a]pyridine To a solution of 8-(4-benzyloxyphenoxy)-6-bromo-imidazo[1,5-a]pyridine (the material from the synthetic step 3 of Int-2a) (1 g, 2.53 mmol) in 1,4-dioxane (10 mL) were added 1,1'- bis(diphenylphosphino)ferrocene-palladium dichloridedichloromethanecomplex (206.61 mg, 253 μmol), 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2-dioxaborolane) (770.98 mg, 3.04 mmol) and potassium acetate (496.6 mg, 5.06 mmol). The reaction was stirred for 15 h at 80oC under nitrogen atmosphere, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by column chromatography to give 8-(4-benzyloxyphenoxy)-6-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,5-a]pyridine(700 mg). MS [M+H]+: 443.2. Step 2: 8-(4-benzyloxyphenoxy)-6-(4-methyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridine To a solution of 8-(4-benzyloxyphenoxy)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2- yl)imidazo[1,5-a]pyridine (100 mg, 226.09 μmol) in 1,4-dioxane (2 mL) and water (0.400 mL) were added 1,1'-bis(diphenylphosphino)ferrocene-palladium dichloridedichloromethanecomplex (18.46 mg, 22.61 μmol), 3-bromo-4-methyl-1,2,4-triazole (43.95 mg, 271.3 μmol) and sodium carbonate (47.93 mg, 452.17 μmol), the reaction was stirred for 15 h at 100oC under nitrogen atmosphere, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purfied by column chromatography to give 8-(4-benzyloxyphenoxy)-6-(4-methyl-1,2,4-triazol-3- yl)imidazo[1,5-a]pyridine(60 mg). MS [M+H]+: 398.2. Step 3: 4-[6-(4-methyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenol (Int-28) A solution of 8-(4-benzyloxyphenoxy)-6-(4-methyl-1,2,4-triazol-3-yl)imidazo[1,5- a]pyridine (60 mg) in TFA (1 mL) was stirred for 3 h at 50oC, cooled to rt and concentrated in vacuum. The residue was used directly in the next step without further purification. MS [M+H]+: 308.1. Intermediate 29a 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5-amine Step 1: 7-bromo-1-methyl-5-nitro-indazole To a mixture of 7-bromo-5-nitro-1H-indazole (25.0 g, 103.29 mmol) and Cs2CO3 (68.0 g, 208.7 mmol) in ACN (250 mL) was added iodomethane (16.0 g, 112.72 mmol). The mixture was stirred at 25 °C for 2 h. The mixture was filtrated and the cake was washed with EtOAc. The combined filtrate was concentrated in vacuum to give crude product, which was purified by column chromatography to give 7-bromo-1-methyl-5-nitro-indazole (10.0 g) as yellow solid.1H NMR (400 MHz, DMSO-d6) δ ppm 8.83 (d, J = 2.0 Hz, 1H), 8.45 (s, 1H), 8.38 (d, J = 2.0 Hz, 1H), 4.39 (s, 3H). Step 2: 1-methyl-5-nitro-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole To a 500 mL flask were added 7-bromo-1-methyl-5-nitro-indazole (10.0 g, 39.05 mmol) and 1,4-dioxane (150 mL). Int-9a (9.3 g, 38.97 mmol), CuI (0.7 g, 3.94 mmol), 2- (dimethylazaniumyl)acetate (1.2 g, 11.64 mmol) and Cs2CO3 (25.0 g, 76.73 mmol) were added at rt to give a brown mixture. The mixture was stirred at 120 °C for 16 h, cooled to rt and quenched with water (200 mL). The aqueous phase was extracted with EA. The combined organic layer was washed with brine, dried over Na2SO4, filtrated and concentrated in vacuum. The residue was purified by prep. HPLC to give 1-methyl-5-nitro-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole (5.8 g) as yellow oil. MS [M+H]+: 414.2. Step 3: 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5-amine (Int- 29a) To a 250 mL flask were added 1-methyl-5-nitro-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole (5.8 g, 14.03 mmol), ethanol (50 mL) and water (10 mL). Iron powder (3.1 g, 56.08 mmol) and NH4Cl (3.0 g, 56.38 mmol) were added into the mixture at rt. The mixture was stirred at 80 °C for 2 h, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by flash column chromatography to give Int-29a (3.9 g) as orange solid. MS [M+H]+: 384.2.1H NMR (400 MHz, DMSO-d6) δ ppm 7.69 (s, 1H), 7.08 - 7.03 (m, 2H), 7.02 - 6.97 (m, 2H), 6.44 (d, J = 1.6 Hz, 1H), 6.14 (d, J = 1.6 Hz, 1H), 4.83 (s, 2H), 4.09 - 4.06 (m, 2H), 4.05 (s, 3H), 3.84 - 3.78 (m, 2H), 3.78 - 3.73 (m, 2H), 3.63 - 3.48 (m, 1H), 3.35 - 3.23 (m, 2H), 1.93 - 1.78 (m, 2H), 1.41 (dtd, J =13.2, 9.6, 4.0 Hz, 2H). Intermediate 29b 5-iodo-1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole Int-29a Int-29bStep 1: 5-iodo-1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole (Int-29b) To a 250 mL flask were added 1-methyl-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazol-5-amine (3.5 g, 9.13 mmol) and 1.5 M HCl(aq)(35.0 mL, 52.50 mmol). The solution was cooled to 0 °C with an ice bath. A solution of NaNO2 (700.0 mg, 10.15 mmol) in water (2 mL) was added to give a brown suspension. The mixture was stirred for 0.5 h at 0 °C. A solution of KI (3.1 g, 18.55 mmol) in water (5 mL) was added dropwise. The resulting mixture was diluted with DCM (5 mL), slowly warmed up to 25 °C and stirred for 16 h. The mixture was adjusted to pH = 8-9 with saturated NaHCO3 solution and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4and filtrated. The filtrate was concentrated in vacuum. The crude product was purified by flash column chromatography to give Int-29b (1.6 g) as yellow oil. MS [M+H]+: 495.1. Intermediate 29c 1-[4-(5-amino-1-methyl-indazol-7-yl)oxyphenyl]-3-methyl-imidazol-2-one 1-[4-(5-amino-1-methyl-indazol-7-yl)oxyphenyl]-3-methyl-imidazol-2-one (Int-29c) was prepared in analogy to Int-29a, by replacing Int-9a with Int-43a in step 2. MS [M+H]+: 336.2. Intermediate 30a Methyl 6-bromo-3-chloro-1-methyl-indazole-5-carboxylate Int-30a To a solution of 6-bromo-1-methyl-indazole-5-carboxylic acid methyl ester (1.5 g, 5.57 mmol) in DMF (25 mL) was added NCS (1.2 g, 8.36 mmol). The mixture was stirred for 16 h at rt. The reaction was quenched with water. The precipitate was filtered, washed with water and dried in vacuum to give Int-30a (1.62 g). MS [M+H]+: 303.0. Intermediate 31a Methyl 6-bromo-3-fluoro-1-methyl-indazole-5-carboxylate Int-31a To a solution of 6-bromo-1-methyl-indazole-5-carboxylic acid methyl ester (0.8 g, 3.00 mmol) in MeCN (25 mL) was added SelectFluor®(1.4 g, 3.90 mmol). The mixture was stirred for 16 h at 90 °C and cooled to rt. The reaction was quenched with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified by flash column chromatography to give Int-31a (184.0 mg). MS [M+H]+: 286.9. Intermediate 32a Methyl 6-bromo-1-cyclopropyl-indazole-5-carboxylate Int-32a To a solution of 6-bromo-1-methyl-indazole-5-carboxylic acid methyl ester (510 mg, 2.00 mmol) in DCE (30 mL) were added cyclopropylboronic acid (344.0 mg, 4.00 mmol), Cu(OAc)2 (364.0 mg, 2.00 mmol), Na2CO3(424.0 mg, 2.00 mmol) and 2,2'-bipyridine (313.0 mg, 2.00 mmol). The mixture was stirred for 16 h at 70 °C, cooled to rt, diluted with ethyl acetate and filtrated through kieselguhr. The filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give the title compound (565.0 mg). MS [M+H]+: 295.0. Intermediate 33a 6-[4-[2-(azetidin-3-yloxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-[2-(azetidin-3-yloxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide (Int-33) was prepared in analogy to Example 140, by replacing tert-butyl 4-(2-hydroxyethoxy)piperidine-1- carboxylate with tert-butyl 3-(2-hydroxyethoxy)azetidine-1-carboxylate in step 1. MS [M+H]+: 383.1. Intermediate 34a 1-methyl-6-[4-(3-piperazin-1-ylpropoxy)phenoxy]indazole-5-carboxamide 1-methyl-6-[4-(3-piperazin-1-ylpropoxy)phenoxy]indazole-5-carboxamide (Int-34a) was prepared in analogy to Example 140, by replacing tert-butyl 4-(2-hydroxyethoxy)piperidine-1- carboxylate with tert-butyl 4-(3-hydroxypropyl)piperazine-1-carboxylate in step 1. MS [M+H]+: 410.1. Intermediate 35a Methyl 6-bromo-1-(2-trimethylsilylethoxymethyl)indazole-5-carboxylate A solution of 2-(chloromethoxy)ethyl-trimethyl-silane (3.14 g, 18.82 mmol), methyl methyl 6-bromo-3H-indazole-5-carboxylate (4 g, 15.68 mmol) and DIPEA (3.04 g, 23.52 mmol) in DCM (100 mL) were stirred at rt for 2 h and concentrated in vacuum. The residue was purified by flash column chromatography to give methyl 6-bromo-1-(2- trimethylsilylethoxymethyl)indazole-5-carboxylate as an oil (5.3 g). MS [M+H]+: 385.0. Intermediate 35b Methyl 6-bromo-1-(difluoromethyl)indazole-5-carboxylate Int-35b A mixture of methyl 6-bromo-3H-indazole-5-carboxylate (1 g, 3.92 mmol), 1- [[bromo(difluoro)methyl]-ethoxy-phosphoryl]oxyethane (1.05 g, 3.92 mmol) and KF (455.56 mg, 7.84 mmol) in CH3CN (20 mL) was stirred at rt for 16 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by flash column chromatography to give methyl 6-bromo-1-(difluoromethyl)indazole-5-carboxylate as yellow solid. MS [M+H]+: 304.9. Intermediate 36a 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-(2-trimethylsilylethoxymethyl)indazole- 5-carboxamide 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-(2-trimethylsilylethoxymethyl) indazole-5-carboxamide (Int-36a) was prepared in analogy to Example 144, by replacing 6- bromo-1-methyl-indazole-5-carboxylate and Int-21d with Int-35a and Int-9a in step 1. MS [M+H]+: 528.0. Intermediate 37a (3-tetrahydropyran-4-yloxycyclobutyl) 4-methylbenzenesulfonateStep 3Int-37a Step 1: (3-benzyloxycyclobutoxy)-trimethyl-silane To a solution of 3-benzyloxycyclobutanol (1.5 g, 8.42 mmol) and TEA (2.6 g, 25.25 mmol) in DCM (20 mL) was added trimethylsilyl chloride (1.0 g, 9.30 mmol) at 0 °C. The reaction was stirred at rt for 1 h, diluted with 30 mL of hexane and filtered. The filtrate was concentrated in vacuum to give crude (3-benzyloxycyclobutoxy)-trimethyl-silane which was used directly in the next step without further purification. MS [M+H]+: 251.2. Step 2: 4-(3-benzyloxycyclobutoxy)tetrahydropyran To a solution of (3-benzyloxycyclobutoxy)-trimethyl-silane (3.0 g, 12 mmol) and tetrahydropyran-4-one (1.2 g, 12 mmol) in DCM (30 mL) were added triethylsilane (1.4 g, 12 mmol) and TMSOTf (1.3 g, 6 mmol) at -78 °C. The resulting solution was allowed to warm slowly to 0 °C and stirred for 1 h at 0 °C. The reaction was quenched with saturated NaHCO3and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash column chromatography to give 4-(3-benzyloxycyclobutoxy)tetrahydropyran. MS [M+ H]+: 263.2. Step 3: 3-tetrahydropyran-4-yloxycyclobutanol To a 100 mL flask were added 4-(3-benzyloxycyclobutoxy)tetrahydropyran (2.9 g, 11.00 mmol) and methanol (50 mL). Pd / C (580 mg, 10% loading) was added in one portion. The suspension was degassed and purged with H2for three times. The resulting mixture was stirred at rt for 12 h under H2 balloon and filtered through a pad of Celite. The cake was washed with MeOH. The combined filtrate was concentrated in vacuum to give 3-tetrahydropyran-4- yloxycyclobutanol (1.7 g) which was used in the next step without further purification. MS [M+H]+: 173.1. Step 4: (3-tetrahydropyran-4-yloxycyclobutyl) 4-methylbenzenesulfonate (Int-37a) To a solution of tosyl chloride (2.9 g, 15.00 mmol) and 3-tetrahydropyran-4- yloxycyclobutanol (1.7 g, 10.0 mmol) in DCM (50 mL) was added TEA (3.0 g, 30.00 mmol). The mixture was stirred at rt for 14 h and diluted with water (40 mL). The mixture was extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified by flash chromatography to give (3- tetrahydropyran-4-yloxycyclobutyl) 4-methylbenzenesulfonate (1.87 g). MS [M+H]+: 327.2. Intermediate 38a [3-[tert-butyl(diphenyl)silyl]oxy-2,2-difluoro-propyl]trifluoromethanesulfonate 12 Int-38a Step 1: 3-[tert-butyl(diphenyl)silyl]oxy-2,2-difluoro-propan-1-ol To a 250 mL three necked flask were added 2,2-difluoropropane-1,3-diol (3.2 g, 28.28 mmol) and THF (32 mL). The flask was degassed and purged with N2gas for four times and cooled to 0 °C with an ice bath. NaH (1.2 g, 28.75 mmol) was added portionwise in 0.5 h. Then tert-butylchlorodiphenylsilane (7.8 g, 28.31 mmol) was added at 0°C. The resulting solution was stirred at rt for 3.5 h and quenched with water. The mixture was extracted with EtOAc. The combined organic layer was dried over Na2SO4, filtered and concentrated in vacuum to give crude product. The crude was purified by flash chromatography to give 3-[tert- butyl(diphenyl)silyl]oxy-2,2-difluoro-propan-1-ol (4.8 g) as colorless oil.1HNMR (400 MHz, DMSO-d6) δ ppm 7.66 - 7.61 (m, 4 H), 7.50 - 7.42 (m, 6 H), 5.55 (t, J = 6.2Hz, 1 H), 3.87 (t, J = 13.0Hz, 2 H), 3.72 (td, J = 13.6, 6.2Hz, 2 H), 1.01 (s, 9 H). Step 2: [3-[tert-butyl(diphenyl)silyl]oxy-2,2-difluoro-propyl]trifluoromethanesulfonate (Int- 38a) To a 100 mL flask were added 3-[tert-butyl(diphenyl)silyl]oxy-2,2-difluoro-propan-1-ol (4.8 g, 13.7 mmol) and DCM (50 mL).2,6-lutidine (1.6 mL, 13.7 mmol) and trifluoromethanesulfonic anhydride (3.9 g, 13.7 mmol) were added at -10 °C. The mixture was stirred at -10 °C for 1 h and quenched witgh 1 M HCl(aq.) (150 mL). The mixture was extracted with DCM. The combined organic layer was washed with sat. sodium bicarbonate, dried over Na2SO4, filtrated and concentrated in vacuu. The crude product was purified by flash chromatography to give [3-[tert-butyl(diphenyl)silyl]oxy-2,2-difluoro- propyl]trifluoromethanesulfonate (4.73 g, 9.8 mmol, 72% yield) as light yellow oil.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.66 (d, J = 6.6 Hz, 4 H), 7.51 - 7.40 (m, 6 H), 4.76 (t, J = 11.4Hz, 2 H), 3.89 (t, J = 11.8Hz, 2 H), 1.09 (s, 9 H). Intermediate 39a 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-[hydroxy-dioxo-(trifluoromethyl)-λ⁷- sulfanyl]phenoxy]imidazo[1,5-a]pyridine Step 1: 5-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carbohydrazide To a solution of Int-3a (500 mg, 1.76 mmol) in methanol (10 mL) was added hydrazine hydrate (4.14 g, 70.36 mmol). The reaction was stirred for 15 h at 80oC, cooled to rt and concentrated in vacuum to give the desired product (500 mg). MS [M+H]+: 285.1. Step 2: N-[(E)-dimethylaminomethyleneamino]-5-(4-hydroxyphenoxy)imidazo[1,5- a]pyridine-7-carboxamide To a solution of 5-(4-hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carbohydrazide (500 mg, 1.76 mmol) in methanol (15 mL) was added N,N-dimethylformamide dimethyl acetal (628.77 mg, 5.28 mmol). The reaction was stirred for 30 min at 50oC, cooled to rt and concentrated in vacuum. The residue was directly used in the next step without further purification. MS [M+H]+: 340.1. Step 3: 4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenol To a solution of N-[(E)-dimethylaminomethyleneamino]-5-(4- hydroxyphenoxy)imidazo[1,5-a]pyridine-7-carboxamide (590 mg, 1.74 mmol) in acetic acid (2 mL) and acetonitrile (10 mL) was added ethylamine hydrochloride (708.83 mg, 8.69 mmol). The reaction was stirred for 20 h at 85oC, cooled to rt and concentrated in vacuum. The residue was basified with aqueous NaHCO3 and extracted with DCM / iPrOH (v / v = 5:1). The organic layer was dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography to give 4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenol (500 mg). MS [M+H]+: 322.1. Step 4: 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-[hydroxy-dioxo-(trifluoromethyl)-λ⁷- sulfanyl]phenoxy]imidazo[1,5-a]pyridine (Int-39a) To a solution of 4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenol (500 mg, 1.56 mmol) in dichloromethane (10 mL) were added triethylamine (472.36 mg, 4.67 mmol) and 1,1,1-trifluoro-N-phenyl-N-triflyl-methanesulfonamide (833.84 mg, 2.33 mmol). The reaction was stirred for 6 h at rt and concentrated in vacuum. The residue was purified by column chromatography to give 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-[hydroxy-dioxo- (trifluoromethyl)-λ⁷-sulfanyl]phenoxy]imidazo[1,5-a]pyridine (560 mg). MS [M+H]+: 454.1. Intermediate 40a 1-(4-hydroxyphenyl)-3-methyl-imidazolidin-2-one Int-40a Step 1: 1-(4-hydroxyphenyl)-3-methyl-imidazolidin-2-one (Int-40a) To a 100 mL flask were added 4-iodophenol (2.0 g, 9.09 mmol) 1,4-dioxane (20 mL), 1- methylimidazolidin-2-one (1.2 g, 11.99 mmol), CuI (100.0 mg, 0.53 mmol), K2CO3(2.5 g, 18.09 mmol) and N,N'-dimethylethane-1,2-diamine (81.21 mg, 0.92 mmol). The mixture was purged with N2 for 1 min at rt and stirred at 110 °C for 16 h. The reaction mixture was cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give 1-(4-hydroxyphenyl)-3-methyl-imidazolidin-2-one (610.0 mg) as light yellow oil. MS [M+H]+: 190.3. Intermediate 40b 1-(4-hydroxyphenyl)pyrrolidin-2-one 1-(4-hydroxyphenyl)pyrrolidin-2-one (Int-40b) was prepared in analogy to Int-40a, by replacing 1-methylimidazolidin-2-one with pyrrolidin-2-one in step 1. MS [M+H]+: 178.1.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.36 - 7.29 (m, 2 H), 6.81 - 6.75 (m, 2 H), 6.50 (s, 1H), 3.82 (t, J = 7.2Hz, 2 H), 2.61 (t, J = 8.0Hz, 2 H), 2.25 - 2.09 (m, 2 H). Intermediate 41a 7-bromo-5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazole Int-41a Step 1: methyl 7-bromo-1-methyl-indazole-5-carboxylate To a solution of methyl 7-bromo-1H-indazole-5-carboxylate (5.8 g, 22.58 mmol) and Cs2CO3 (14.7 g, 45.16 mmol) in ACN (60 mL) was added iodomethane (3.2 g, 22.58 mmol). The mixture was stirred at 20 °C for 2 h. The mixture was diluted with water (30 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum. The crude was purified by flash chromatography to give methyl 7-bromo-1-methyl- indazole-5-carboxylate (3.28 g) as yellow solid. MS [M+H]+: 269.0.1H NMR (400 MHz, DMSO-d6) δ ppm 8.48 (d, J = 1.2 Hz, 1 H), 8.33 (s, 1 H), 8.08 (d, J = 1.2 Hz, 1 H), 4.36 (s, 3 H), 3.88 (s, 3 H). Step 2: 7-bromo-1-methyl-indazole-5-carbohydrazide To a 500 mL vial tube equipped with a magnetic stir bar were added methyl 7-bromo-1- methyl-indazole-5-carboxylate (10.0 g, 37.16 mmol), ethanol (150 mL) and NHNH•HO (25.0 g, 499.4 mmol). The mixture was stirred at 80 °C for 4 h, cooled to 25 °C and diluted with water (200 mL). The solid was collected by filtration, washed with water and dry to constant weight at 40 °C to give the 7-bromo-1-methyl-indazole-5-carbohydrazide (9.0 g) as yellow solid. MS [M+H]+: 268.9.1H NMR (400 MHz, DMSO-d) δ ppm 9.87 (s, 1H), 8.30 (d, J = 1.2Hz, 1 H), 8.26 (s, 1H), 8.07 (d, J = 1.2Hz, 1 H), 4.52 (br s, 2 H), 4.34 (s, 3 H). Step 3: 7-bromo-5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazole (Int-41a) To a 250 mL flask equipped with a magnetic stir bar were added 7-bromo-1-methyl- indazole-5-carbohydrazide (9.0 g, 33.44 mmol), acetic acid (9 mL), ethanamine;hydrochloride (13.5 g, 165.56 mmol), DMFDMA (9.0 g, 75.53 mmol) and ACN (90 mL). The mixture was stirred at 80 °C for 16 h, cooled to 25 °C and concentrated under reduced pressure. The crude product was purified by prep-HPLC to give Int-41a (9.0 g) as yellow solid. MS [M+H]+: 306.2. Intermediate 42a 1-cyclopropylimidazolidin-2-one Step 1: 1-(2-chloroethyl)-3-cyclopropyl-urea To a 250 mL three neck-flask equipped with a magnetic stir bar were added cyclopropylamine (6.07 mL, 87.57 mmol) and THF (100 mL). To the solution was added dropwise 2-chloroethyl isocyanate (9.24 g, 87.57 mmol). The mixture was stirred at 20 °C for 2 h, concentrated to dryness and triturated in acetonitrile. The precipitate was collected by filtration and dried in vacuum to afford 1-(2-chloroethyl)-3-cyclopropyl-urea (10.0 g) as white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 6.28 (s, 1 H), 6.12 (s, 1 H), 3.56 (t, J = 6.4Hz, 2 H), 3.32 - 3.24 (m, 2 H), 2.50 – 2.36 (m, 1 H), 0.60 - 0.48 (m, 2 H), 0.38 - 0.24 (m, 2 H). Step 2: 1-cyclopropylimidazolidin-2-one (Int-42a) To a 500 mL three-neck flask equipped with a magnetic stir bar were added 1-(2- chloroethyl)-3-cyclopropyl-urea (10.0 g, 61.49 mmol) and THF (120 mL). The solution was exchange with N2over a period of three minutes and then cooled to 0 °C with an ice bath. To the solution was added NaH (3.0 g, 75.0 mmol) in one potion at 0 °C under N2. The mixture was stirred at 20 °C for 6 h and then quenched with slow addition of sat. NH4Cl solution with stirring. The aqueous phase was extracted with ethyl acetate. The combined organic layer was washed with brine and concentrated under reduced pressure to afford Int-42a (5.6 g) as white solid.1H NMR (400 MHz, DMSO-d6) δ ppm 6.28 (s, 1 H), 3.30 - 3.28 (m, 2 H), 3.20 - 3.08 (m, 2 H), 2.34 - 2.24 (m, 1 H), 0.58 - 0.46 (m, 4 H). Intermediate 43a 1-(4-hydroxyphenyl)-3-methyl-imidazol-2-one To a 40 mL via tube equipped with a magnetic stir bar were added 4-iodophenol (1.8 g, 8.18 mmol), 1,4-dioxane (10 mL), 3-methyl-1H-imidazol-2-one (1.1 g, 11.01 mmol), CuI (90.0 mg, 0.47 mmol), K2CO3 (2.25 g, 16.28 mmol) and N,N'-dimethylethane-1,2-diamine (90.0 mg, 1.02 mmol). The mixture was purged with N2for 1 min, stirred at 100 °C for 6 h, cooled to rt and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography to give Int-43a (700.0 mg) as yellow solid. MS [M+H]+: 191.0. Intermediate 43b 1-ethyl-3-(4-hydroxyphenyl)imidazolidin-2-one 1-ethyl-3-(4-hydroxyphenyl)imidazolidin-2-one (Int-43b) was prepared in analogy to Int- 43a, by replacing 3-methyl-1H-imidazol-2-one with 1-ethylimidazolidin-2-one in step 1. MS [M+H]+: 207.1. Intermediate 43c 5-(4-hydroxyphenyl)-5-azaspiro[2.4]heptan-4-one 5-(4-hydroxyphenyl)-5-azaspiro[2.4]heptan-4-one (Int-43c) was prepared in analogy to Int- 43a, by replacing 3-methyl-1H-imidazol-2-one with 5-azaspiro[2.4]heptan-4-one in step 1. MS [M+H]+: 204.1. Intermediate 43d 1-cyclopropyl-3-(4-hydroxyphenyl)imidazolidin-2-one 1-cyclopropyl-3-(4-hydroxyphenyl)imidazolidin-2-one (Int-43d) was prepared in analogy to Int-43a, by replacing 3-methyl-1H-imidazol-2-one with Int-42a in step 1. MS [M+H]+: 219.2. Intermediate 44a 1-(4-hydroxyphenyl)-3-(2-methoxyethyl)imidazolidin-2-one Step 1: 1-(4-benzyloxyphenyl)-3-(2-chloroethyl)urea To a solution of 4-benzyloxyaniline (15.0 g, 75.28 mmol) in DCM (200 mL) was added 2- chloroethyl isocyanate (9.0 g, 85.29 mmol) at 0 °C. The solution was stirred at 20 °C for 12 h and then concentrated in vacuum to give 1-(4-benzyloxyphenyl)-3-(2-chloroethyl)urea (20.0 g) as off-white solid. MS [M+H]+: 305.0. Step 2: 1-(4-benzyloxyphenyl)imidazolidin-2-one To a 500 mL flask equipped with a magnetic stir bar were added 1-(4-benzyloxyphenyl)-3- (2-chloroethyl)urea (5.0 g, 65.62 mmol), THF (250 mL) and DMF (10 mL). The flask was then evacuated and backfilled with nitrogen for three times. The solution was cooled to 0 °C with an ice bath. NaH (750.0 mg, 25.0 mmol) was added in portions over a period of 3 min. Then KI (250.0 mg, 1.51 mmol) was added at 20 °C to give a yellow suspension. The mixture was stirred at 20 °C for 16 h and quenched with saturated NH4Cl. The precipitate was collected by filtration and dried in vacuum to give 1-(4-benzyloxyphenyl)imidazolidin-2-one (16.0 g) as white solid. MS [M+H]+: 269.1. Step 3: 1-(4-benzyloxyphenyl)-3-(2-methoxyethyl)imidazolidin-2-one To a 250 mL three necked flask equipped with a magnetic stir bar were added 1-(4- benzyloxyphenyl)imidazolidin-2-one (7.0 g, 26.09 mmol) and DMF (70 mL). The flask was evacuated and backfilled with nitrogen for three times. The solution was cooled to 0 °C with an ice bath. NaH (0.9 g, 39.13 mmol) was added over a period of 1 min at 0 °C. The resulting mixture was stirred at 0 °C for 0.5 h. A solution of 1-bromo-2-methoxy-ethane (3.6 g, 26.09 mmol) in THF (10 mL) was added dropwise at 0 °C. The mixture was stirred at 25 °C for 16 h., quenched with saturated NH4Cl solution and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuum to obtain 1-(4-benzyloxyphenyl)-3-(2-methoxyethyl)imidazolidin-2-one (3.0 g) as yellow solid. MS [M+H]+: 327.1. Step 4: 1-(4-hydroxyphenyl)-3-(2-methoxyethyl)imidazolidin-2-one (Int-44a) To a 250 mL hydrogenation bottle equipped with a magnetic stir bar were added Pd / C (300 mg, 10 % loading) and methanol (3 mL) under Ar.1-(4-benzyloxyphenyl)-3-(2- methoxyethyl)imidazolidin-2-one (3.0 g, 9.19 mmol) in methanol (30 mL) was added at 25 °C. The suspension was degassed and purged with H2for three times, stirred at 25 °C for 16 h under H2 (50 psi) and filtered through a Celite pad. The cake was washed with MeOH. The fiitrate was concentrated in vacuum to give Int-44a (2.0 g) as white solid. MS [M+H]+: 237.1. Intermediate 44b 1-(cyclopropylmethyl)-3-(4-hydroxyphenyl)imidazolidin-2-one 1-(cyclopropylmethyl)-3-(4-hydroxyphenyl)imidazolidin-2-one (Int-44b) was prepared in analogy to Int-44a, by replacing 1-bromo-2-methoxy-ethane with bromomethylcyclopropane in step 3. MS [M+H]+: 233.1. Intermediate 44c 1-(4-hydroxyphenyl)-3-(oxetan-3-ylmethyl)imidazolidin-2-one 1-(4-hydroxyphenyl)-3-(oxetan-3-ylmethyl)imidazolidin-2-one (Int-44c) was prepared in analogy to Int-44a, by replacing 1-bromo-2-methoxy-ethane with Int-8x in step 3. MS [M+H]+: 249.2. Intermediate 45a 1-(4-hydroxyphenyl)-3-(oxetan-3-ylmethyl)imidazol-2-one Step 1: 1-(4-benzyloxyphenyl)-3-(2,2-diethoxyethyl)urea To a 1 L three neck flask equipped with a magnetic stir bar were added 4- benzyloxyaniline;hydrochloride (50.0 g, 212.13 mmol) and DCM (250 mL). To the solution was added dropwise a solution of N, N'-carbonyldiimidazole (39.0 g, 240.52 mmol) in DCM (500 mL) over a period of 1 h at 0 °C. The misture was stirred at 0 °C for 2 h to give a white suspension. To the suspension was added 2,2-diethoxyethanamine (28.4 g, 212.82 mmol) dropwise over a period of 0.3 h at 0 °C. The resulting solution was stirred at 20 °C for 2 h and concentrated under reduced pressure. The residue was purified by flash chromatography to give 1-(4-benzyloxyphenyl)-3-(2,2-diethoxyethyl)urea (65.0 g) as white solid. MS [M+H]+: 359.0. Step 2: 3-(4-benzyloxyphenyl)-1H-imidazol-2-one To a 1 L flask equipped with a magnetic stir bar were added 1-(4-benzyloxyphenyl)-3-(2,2- diethoxyethyl)urea (34.0 g, 94.86 mmol) and methanol (200 mL). HCl (150.0 mL, 225.0 mmol) was added. The mixture was stirred at 20 °C for 12 h. The precipitate was collected by suction filtration, washed with cold water and dried to constant weight at 50 °C to give 3-(4- benzyloxyphenyl)-1H-imidazol-2-one (22.0 g) as off-white soild. MS [M+H]+: 436.3. Step 3: 1-(4-benzyloxyphenyl)-3-(oxetan-3-ylmethyl)imidazol-2-one To a 250 mL three necked flask equipped with a magnetic stir bar were added 3-(4- benzyloxyphenyl)-1H-imidazol-2-one (5.5 g, 20.65 mmol) and DMF (60 mL). The flask was evacuated and backfilled with nitrogen for three times. The solution was cooled to 0 °C with an ice bath. NaH (9.5 g, 41.31 mmol) was added at 0 °C in protions. The mixture was stirred for 2 h. Int-8x (5.5 g, 22.72 mmol) was added at 0 °C. The resulting mixture was stirred at 20 °C for 16 h under N2 atmosphere and quenched with saturated aqueous ammonium chloride. The aqueous phase was extracted with EtOAc. The extracts were washed with brine, dried over anhydrous Na2SO4 and filtrated. The filtrate was concentrated in vacuum. The crude product was purified by Prep-HPLC to give 1-(4-benzyloxyphenyl)-3-(oxetan-3-ylmethyl)imidazol-2-one (5.0 g) as yellow oil. MS [M+H]+: 337.2. Step 4: 1-(4-hydroxyphenyl)-3-(oxetan-3-ylmethyl)imidazol-2-one (Int-45a) To a 35 mL hydrogenation bottle equipped with a magnetic stir bar was added Pd / C (100 mg) and methanol (2 mL).1-(4-benzyloxyphenyl)-3-(oxetan-3-ylmethyl)imidazol-2-one (1.0 g, 2.97 mmol) in ethyl acetate (10 mL) was added at 25 °C. The flask was evacuated and backfilled with Ar for three times and then evacuated and backfilled with H2 for another three times. The mixture was stirred at 25 °C for 1 h (under 10 psi hydrogen atmosphere). The suspension was filtered through a Celite pad and the cake was washed with methanol. The filtrate was concentrated to give Int-45a (800.0 mg) as orange oil. MS [M+H]+: 247.1.1H NMR (400 MHz, DMSO-d6) δ = 9.97 - 9.06 (m, 1H), 7.42 - 7.38 (m, 2H), 6.84 (d, J = 3.2Hz, 1H), 6.80 (d, J = 8.8Hz, 2H), 6.71 (d, J = 3.2Hz, 1H), 4.63 (dd, J = 6.0, 8.0Hz, 2H), 4.38 (t, J = 6.0Hz, 2H), 3.86 (d, J = 7.2Hz, 2H), 3.30 - 3.24 (m, 1H). Intermediate 45b 1-(4-hydroxyphenyl)-3-(1-methylcyclopropyl)imidazol-2-one 1-(4-hydroxyphenyl)-3-(1-methylcyclopropyl)imidazol-2-one (Int-45b) was prepared in analogy to Int-45a, by replacing 2,2-diethoxyethanamine with N-(2,2-diethoxyethyl)-1-methyl- cyclopropanamine in step 1. MS [M+H]+: 231.2. Example 1 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-1a and Int-7a according to the following scheme: Step 1: methyl 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxylate (compound 1.1) To a solution of Int-1a (40.0 mg, 0.13 mmol) and Int-7a (92.0 mg, 0.7 mmol) in toluene (1 mL) was added 2-(tributylphosphanylidene)acetonitrile (82.0 mg, 0.34 mmol). The suspension was degassed and purged with N2 three times and stirred at 90 °C for 12 h under N2. The mixture was cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give compound 1.1 (50.0 mg) as brown oil. MS [M+H]+: 413.1. Step 2: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxylic acid (compound 1.2) To an 8 mL vial were added compound 1.1 (160.0 mg, 0.39 mmol) and methanol (1 mL). LiOH•H2O (63.6 mg, 1.55 mmol) and water (0.2 mL) were added. The mixture was stirred at 25 °C for 2 h. The mixture was adjusted to pH = 5~7 with 1M HCl aqueous solution and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum to give compound 1.2 (150.0 mg) which was used directly in the next step without further purification. MS [M+H]+: 399.3. Step 3: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide (Example 1) To an 8 mL vial were added compound 1.2 (0.4 g, 1.0 mmol), HATU (0.42 g, 1.1 mmol), NH4Cl (0.27 g, 5.09 mmol) and DIEA (0.26 g, 2.01 mmol) in DMF (4 mL). The mixture was stirred at 20 °C for 2 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by reverse-phase chromatography to give Example 1 (70.0 mg) as colorless oil. MS [M+H]+: 398.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (s, 1 H), 7.96 (br s, 1 H), 7.26 (br s, 1 H), 7.17 (s, 1 H), 7.08 - 7.13 (m, 2 H), 7.00 - 7.06 (m, 2 H), 4.21 (s, 4 H), 4.09 (t, J = 4.4 Hz, 2 H), 3.63 - 3.75 (m, 6 H), 1.85 - 2.02 (m, 2 H). Example 2 1-methyl-7-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-1a according to the following scheme: Step 1: methyl 7-[4-[2-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl- indazole-5-carboxylate (compound 2.1) To an 8 vial were added Int-1a (35.0 mg, 0.12 mmol), toluene (1 mL).2- (tributylphosphanylidene)acetonitrile (75.0 mg, 0.31 mmol) and tert-butyl 4-(2- hydroxyethoxy)piperidine-1-carboxylate (32.0 mg, 0.13 mmol). The suspension was degassed and purged with N2 three times and stirred at 90 °C for 2 h under N2. The mixture was filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give compound 2.1 (60.0 mg) as brown oil, which was used in the next step directly without further purification. MS [M-Boc+H]+: 426.2. Step 2: 7-[4-[2-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl- indazole-5-carboxylic acid (compound 2.2) To a mixture of compound 2.1 (60.0 mg, 0.11 mmol) and LiOH•H2O (15.0 mg, 0.37 mmol) in methanol (1 mL) was added water (0.2 mL). The mixture was stirred at 20 °C for 1 h, adjusted to pH = 3-4 with 1M HCl aqueous solution and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum to give compound 2.2 (50.0 mg, 0.1 mmol, 85.62% yield) which was used in the next step without further purification. MS [M-Boc+H]+: 412.2. Step 3: tert-butyl 4-[2-[4-(5-carbamoyl-1-methyl-indazol-7-l)oxyphenoxy]ethoxy]piperidine- 1-carboxylate (compound 2.3) To a solution of compound 2.2 (350 mg, 0.68 mmol) were added NH4Cl (180 mg, 3.42 mmol), HATU (520 mg, 1.37 mmol) and DIEA (180 mg, 1.37 mmol) in DMF (4 mL). The mixture was stirred at 20 °C for 1 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by prep-TLC to give compound 2.3 (0.35 g) as brown oil. MS [M- Boc+H]+: 411.2. Step 4: 1-methyl-7-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide (Example 2) To an 8 mL vial were added compound 2.3 (0.35 g, 0.69 mmol) and 4 M HCl in dioxane (1 mL). The mixture was stirred at 20 °C for 0.5 h. and concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 2 (59.0 mg) as colorless oil. MS [M+H]+: 411.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.77 - 9.09 (m, 2 H), 8.20 (s, 1 H), 8.07 (d, J = 1.2 Hz, 1 H), 7.93 - 8.04 (m, 1 H), 7.22 - 7.33 (m, 1 H), 7.09 - 7.16 (m, 3 H), 7.01 - 7.06 (m, 2 H), 4.19 - 4.23 (m, 3 H), 4.08 - 4.16 (m, 2 H), 3.78 - 3.80 (m, 2 H), 3.63 - 3.68 (m, 1 H), 3.07 - 3.21 (m, 2 H), 2.88 - 3.01 (m, 2 H), 1.93 - 2.02 (m, 2 H), 1.63 (br d, J = 8.0 Hz, 2 H). Example 3 1-methyl-7-[4-[2-[(1-methyl-4-piperidyl)oxy]ethoxy]phenoxy]indazole-5-carboxamide The titled compound was synthesized from Example 2 according to the following scheme: To a solution of Example 2 (50.0 mg, 0.12 mmol) in methanol were added polyformaldehyde (7.31 mg, 0.24 mmol) and NaBH3CN (30 mg, 0.37 mmol). The mixture was stirred at 20 °C for 2 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 3 (6.4 mg) as colorless oil. MS [M+H]+: 425.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 2 H), 8.06 (d, J = 1.2Hz, 1 H), 7.97 (br s, 1 H) 7.26 (br s, 1 H), 7.16 (d, J = 1.2 Hz, 1 H), 7.09 - 7.12 (m, 2 H), 7.01 - 7.05 (m, 2 H), 4.21 (s, 3 H), 4.07 - 4.11 (m, 2 H), 3.72 - 3.76 (m, 2 H), 3.43 (br s, 1 H), 2.74 - 2.82 (m, 2 H), 2.28 - 2.35 (m, 5 H), 1.87 (br d, J = 11.2 Hz, 2 H), 1.50 - 1.60 (m, 2 H). Example 4 and Example 5 1-methyl-7-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide and 1-methyl-7-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5- carboxamide The titled compounds were prepared from Example 1 according to the following scheme: Example 4 & Example 5 Example 1 (40.0 mg, 0.1 mmol) was purified by SFC (column: Chiralpak AY-350*4.6 mm I.D., 3um; mobile phase: phase A for CO2and phase B for EtOH (0.05% DEA); gradient elution: 60% EtOH (0.05% DEA) in CO2; flow rate: 3 mL / min; detector: PDA; column temperature: 35 °C; back pressure: 100 bar) to get the two enantiomers. Example 4 (9.1 mg), the faster fraction, colorless oil. MS [M+H]+: 398.2.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.05 (s, 1 H), 7.87 (d, J = 1.2 Hz, 1 H), 7.12 (d, J = 1.2 Hz, 1 H), 7.00 - 7.07 (m, 2 H), 6.92 - 6.99 (m, 2 H), 4.33 (s, 3 H), 4.26 (dt, J = 4.8, 2.0Hz, 1 H), 4.13 (t, J = 4.8 Hz, 2 H), 3.93 (q, J = 7.6Hz, 1 H), 3.89 (br d, J = 2.4 Hz, 5 H), 2.00 - 2.10 (m, 2 H). Example 5 (10.7 mg), the slower fraction, colorless oil. MS [M+H]+: 398.2.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.05 (s, 1 H), 7.87 (d, J = 1.2Hz, 1 H), 7.12 (d, J = 1.2Hz, 1 H), 7.01 - 7.07 (m, 2 H), 6.92 - 6.99 (m, 2 H), 4.33 (s, 3 H), 4.26 (dt, J = 4.8, 2.4Hz, 1 H), 4.13 (t, J = 4.8Hz, 2 H), 3.76 - 3.97 (m, 6 H), 1.99 - 2.10 (m, 2 H). Example 6 5-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Example 6) was prepared in analogy to Example 1, by replacing Int-1a with Int-3a in step 1. MS [M+H]+: 384.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.59 (s, 1 H), 8.01 (br s, 1 H), 7.95 (s, 1 H) 7.69 (s, 1 H), 7.37 (br s, 1 H), 7.33 (d, J = 9.0 Hz, 2 H), 7.09 (d, J = 9.0Hz, 2 H), 6.09 (s, 1 H), 4.22 (m, 1 H), 4.14 (t, J = 4.4Hz, 2 H), 3.65 - 3.76 (m, 6 H), 1.86 - 2.00 (m, 2 H). Example 7 5-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide 5-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide (Example 7) was prepared in analogy to Example 9, by replacing Int-1b and Int- 8a with Int-3a and Int-8w in step 1. Yellow solid, MS [M+H]+: 384.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.59 (s, 1 H), 8.02 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.39 (br s, 1 H), 7.33 (d, J = 9.2Hz, 2 H), 7.09 (d, J = 8.8Hz, 2 H), 6.07 (s, 1 H), 4.22 (m,1 H), 4.14 (t, J = 4.8Hz, 2 H), 3.77 - 3.64 (m, 6 H), 2.02 – 1.86 (m, 2 H). Example 8 5-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide The titled compound was prepared from Example 6 according to the following scheme: Example 6 (125.0 mg, 0.33 mmol) was purified by SFC (column: DAICEL CHIRALPAK AY-H (250 mm*30 mm,10 μm); mobile phase: phase A for CO2and phase B for EtOH (0.1% NH3^H2O); gradient elution: 35% EtOH (0.05% DEA) in CO2; flow rate:150 mL / min; detector: PDA; column temperature: 35 °C; back pressure: 100 bar) to get the Example 8 (40.0 mg), white solid. Rt = 2.112 min. MS [M+H]+: 384.2.1HNMR (400 MHz, DMSO-d6) δ ppm 8.59 (s, 1 H), 8.01 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.37 (br s, 1 H), 7.33 (d, J = 9.0 Hz, 2 H), 7.09 (d, J = 9.0Hz, 2 H), 6.08 (s, 1 H), 4.22 (m, 1 H), 4.14 (t, J = 4.6Hz, 2 H), 3.64 - 3.78 (m, 6 H), 1.87 - 2.02 (m, 2 H). Example 9 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-1b and Int-8a according to the following scheme: Step 1: methyl 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxylate (compound 9.1) To a solution of Int-8a (30.0 mg, 0.2 mmol) and Int-1b (60.0 mg, 0.2 mmol) in ACN (1 mL) was added K2CO3(90.0 g, 0.6 mmol). The mixture was stirred at 80 °C for 16 h, cooled to rt and filtered. The filtrate was concentrated in vacuum to give compound 9.1 (70.0 mg). MS [M+H]+: 427.2. Step 2: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxylic acid (compound 9.2) To a mixture of compound 9.1 (70.0 mg, 0.18 mmol) and LiOH•H2O (40.0 g, 0.89 mmol) in methanol (1 mL) was added water (0.2 mL). The mixture was stirred at 20 °C for 2 h to give a yellow suspension. The mixture was adjusted to pH = 3-4 with 1M HCl aqueous solution and filtered. The cake was collected and dried in vacuum. The crude was purified by reversed-phase chromatography to give compound 9.2 (30.0 mg) as brown solid. MS [M+H]+: 413.2. Step 3: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide (Example 9) To an 8 mL vial were added compound 9.2 (30.0 mg, 0.08 mmol) DMF (1 mL). HATU (60.3 mg, 0.16 mmol), NH4Cl (21.0 mg, 0.4 mmol) and DIEA (20.5 mg, 0.16 mmol). The mixture was stirred at 20 °C for 2 h and concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 9 (11.3 mg) as white solid. MS [M+H]+: 412.2.1H NMR (500 MHz, METHANOL-d4) δ = 8.32 (s, 1H), 7.97 (d, J = 0.9 Hz, 1H), 7.04 - 7.00 (m, 2H), 6.97 - 6.93 (m, 2H), 6.67 (s, 1H), 4.07 - 4.03 (m, 2H), 3.86 - 3.80 (m, 2H), 3.77 - 3.75 (m, 5H), 3.56 (tt, J = 4.2, 8.7 Hz, 1H), 3.41 - 3.34 (m, 2H), 1.89 - 1.82 (m, 2H), 1.52 - 1.44 (m, 2H). Example 11 7-[4-(cyclopropylmethoxy)phenoxy]-1-methyl-indazole-5-carboxamide 7-[4-(cyclopropylmethoxy)phenoxy]-1-methyl-indazole-5-carboxamide (Example 11) was prepared in analogy to Example 9, by replacing Int-8a and Int-1b with iodomethylcyclopropane and Int-1a in step 1. White solid, MS [M+H]+: 338.3.1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.06 (s, 1 H), 8.03 (s, 1 H), 7.87 (s, 1 H), 7.11 (s, 1 H), 7.02 - 7.07 (m, 2 H), 6.92 - 6.97 (m, 2 H), 5.62 - 6.12 (m, 2 H), 4.34 (s, 3 H), 3.82 (d, J = 7.2Hz, 2 H), 1.27 - 1.33 (m, 1 H), 0.63 - 0.72 (m, 2 H), 0.35 - 0.42 (m, 2 H). Example 16 1-methyl-7-[4-[2-(1,2,4-triazol-4-yl)ethoxy]phenoxy]indazole-5-carboxamide 1-methyl-7-[4-[2-(1,2,4-triazol-4-yl)ethoxy]phenoxy]indazole-5-carboxamide (Example 16) was prepared in analogy to Example 9, by replacing Int-8a and Int-1b with Int-8d and Int- 1a in step 1. White solid, MS [M+H]+: 379.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.78 (s, 2 H), 8.20 (s, 1 H), 8.07 (d, J = 0.8Hz, 1 H), 7.95 (br s, 1 H), 7.26 (br s, 1 H), 7.16 (s, 1 H), 7.09 - 7.14 (m, 2 H), 7.01 - 7.07 (m, 2 H), 4.50 (t, J = 4.8Hz, 2 H), 4.32 (t, J = 5.2Hz, 2 H), 4.20 (s, 3 H). Example 17 1-methyl-7-[4-[2-(2-oxopyrrolidin-1-yl)ethoxy]phenoxy]indazole-5-carboxamide 1-methyl-7-[4-[2-(2-oxopyrrolidin-1-yl)ethoxy]phenoxy]indazole-5-carboxamide (Example 17) was prepared in analogy to Example 9, by replacing Int-8a and Int-1b with Int-8e and Int- 1a in step 1. White solid, MS [M+H]+: 395.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (d, J = 1.2Hz, 1 H), 7.97 (brs, 1 H), 7.29 (br s, 1 H), 7.16 (d, J = 1.0Hz, 1 H), 7.08 - 7.13 (m, 2 H), 7.00 - 7.05 (m, 2 H), 4.21 (s, 3 H), 4.09 (t, J = 5.4Hz, 2 H), 3.55 (t, J = 5.4Hz, 2 H), 3.47 (t, J = 7.0Hz, 2 H), 2.22 (t, J = 8.0Hz, 2 H), 1.85 - 1.98 (m, 2 H). Example 18 1-methyl-7-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-7-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide (Example 18) was prepared in analogy to Example 9, by replacing Int-8a and Int-1b with Int- 8f and Int-1a in step 1. White solid,1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (d, J = 1.0Hz, 1 H), 7.98 (br s, 1 H), 7.26 - 7.32 (m, 1 H), 7.26 - 7.32 (m, 1 H), 7.15 (d, J = 0.8Hz, 1 H), 7.07 - 7.14 (m, 2 H), 7.00 (d, J = 9.0Hz, 2 H), 4.21 (s, 3 H), 3.97 (t, J = 6.2Hz, 2 H), 3.36 (br s, 2 H), 2.16 - 2.26 (m, 2 H), 1.87 - 1.96 (m, 4 H). Example 19 1-methyl-7-[4-[2-(3-methyl-2-oxo-imidazolidin-1-yl)ethoxy]phenoxy]indazole-5- carboxamide 1-methyl-7-[4-[2-(3-methyl-2-oxo-imidazolidin-1-yl)ethoxy]phenoxy]indazole-5- carboxamide (Example 19) was prepared in analogy to Example 9, by replacing Int-8a and Int- 1b with Int-14a and Int-1a in step 1. White solid, MS [M+H]+: 410.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (d, J = 1.2Hz, 1 H), 7.97 (br s, 1 H), 7.27 (br s, 1 H), 7.17 (d, J = 1.0Hz, 1 H), 7.08 - 7.14 (m, 2 H), 6.99 - 7.06 (m, 2 H), 4.21 (s, 3 H), 4.07 (t, J = 5.4Hz, 2 H), 3.45 (t, J = 5.4Hz, 2 H), 3.37 - 3.42 (m, 2 H), 3.21 - 3.27 (m, 2 H), 2.65 (s, 3 H). Example 21 7-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 7-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 21) was prepared in analogy to Example 9, by replacing Int-1b and Int- 8a with Int-1c and Int-8a in step 1. White solid, MS [M+H]+: 430.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.22 (s, 1 H), 8.11 (s, 1 H), 7.98 (br s, 1 H), 7.31 (br s, 1 H), 7.18 - 7.28 (m, 3 H), 6.91 (br d, J = 8.8Hz, 1 H), 4.16 - 4.21 (m, 5 H), 3.76 - 3.85 (m, 4 H), 3.52 - 3.62 (m, 1 H), 3.36 (br d, J = 2.4Hz, 1 H), 3.30 (br d, J = 2.2Hz, 1 H), 1.82 - 1.91 (m, 2 H), 1.34 - 1.47 (m, 2 H). Example 22 7-[3-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 7-[3-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide ((Example 22) was prepared in analogy to Example 9, by replacing Int-1b and Int-8a with Int-1d and Int-8a in step 1. White solid, MS [M+H]+: 446.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.21 (s, 1 H), 8.10 (d, J = 1.0Hz, 1 H), 7.98 (br s, 1 H), 7.35 (d, J = 2.8Hz, 1 H), 7.30 (br s, 1 H), 7.25 (d, J = 9.0Hz, 1 H), 7.21 (d, J = 1.0Hz, 1 H), 7.11 (dd, J = 9.0, 2.8Hz, 1 H), 4.16 - 4.22 (m, 5 H), 3.80 (q, J = 5.0Hz, 4 H), 3.58 - 3.66 (m, 1 H), 3.36 (br d, J = 2.8Hz, 2 H), 1.82 - 1.91 (m, 2 H), 1.42 (dtd, J = 13.2, 9.4, 9.2, 4.2Hz, 2 H). Example 23 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Example 23) was prepared in analogy to Example 9, by replacing Int-1b and Int-8a with Int- 3a and Int-8a in step 1. Off-white solid, MS [M+H]+: 398.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.58 (s, 1 H), 8.00 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.35 (br d, J = 6.8 Hz, 1 H), 7.29 - 7.34 (m, 2 H),, 7.06 - 7.12 (m, 2 H), 6.08 (d, J = 0.8 Hz, 1 H), 4.07 - 4.19 (m, 2 H), 3.72 - 3.88 (m, 4 H), 3.52 - 3.62 (m, 1 H), 3.36 - 3.38 (m, 2 H), 1.79 - 1.93 (m, 2 H), 1.42 (dtd, J =13.2, 9.4, 9.4, 4.2 Hz, 2 H). Example 24 8-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6-carboxamide 8-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6-carboxamide (Example 24) was prepared in analogy to Example 9, by replacing Int-1b and Int-8a with Int- 2a and Int-8a in step 1. Off-white solid, MS [M+H]+: 398.1.1H NMR (400 MHz, DMSO-d6): δ ppm 8.96 (br s, 1 H), 8.75 (s, 1 H), 8.05 (br s, 1 H), 7.74 (br s, 1 H), 7.52 (br s, 1 H), 7.18 (d, J = 9.2 Hz, 2 H), 7.05 (d, J = 8.8 Hz, 2 H), 6.42 (s, 1 H), 4.12 (t, J = 4.4 Hz, 2 H), 3.70 - 3.90 (m, 5 H), 3.29 - 3.35 (m, 2 H), 1.79 - 1.94 (m, 2 H), 1.33 - 1.49 (m, 2 H). Example 25 3-methyl-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide 3-methyl-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide (Example 25) was prepared in analogy to Example 9, by replacing Int-1b and Int- 8a with Int-3b and Int-8a in step 1. Off-white solid, MS [M+H]+: 412.2.1H NMR (400 MHz, DMSO-d6) δ ppm 7.93 (br s, 1 H), 7.82 (s, 1 H), 7.48 (s, 1 H), 7.22 - 7.34 (m, 3 H), 7.07 (d, J = 9.0Hz, 2 H), 5.97 (s, 1 H), 4.05 - 4.18 (m, 2 H), 3.73 - 3.86 (m, 4 H), 3.52 - 3.61 (m, 1 H), 3.35 - 3.37 (m, 2 H), 2.86 (s, 3 H), 1.81 - 1.95 (m, 2 H), 1.41 (m, 2 H). Example 26 1-methyl-8-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6- carboxamide 1-methyl-8-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6- carboxamide (Example 26) was prepared in analogy to Example 9, by replacing Int-1b and Int- 8a with Int-2b and Int-8g in step 1. White solid, MS [M+H]+: 398.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.56 (s, 1 H), 8.40 (s, 1 H), 7.90 (br d, J = 1.2Hz, 1 H), 7.31 - 7.42 (m, 1 H), 7.13 (d, J = 9.0Hz, 2 H), 7.02 (d, J = 9.0Hz, 2 H), 6.13 (s, 1 H), 4.17 - 4.24 (m, 1 H), 4.10 (t, J = 4.4Hz, 2 H), 3.63 - 3.75 (m, 6 H), 2.52 (br s, 3 H), 1.88 - 1.99 (m, 2 H). Example 28 5-[4-[3-(3-methylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide The titled compound was synthesized from Int-6b according to the following scheme: Step 1: methyl 5-[4-[3-(3-methylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine- 7-carboxylate (compound 28.1) To an 8 mL vial were added Int-6b (120.0 mg, 0.33 mmol), DMF (1 mL), 3- methylmorpholine (240.0 mg, 2.37 mmol), K2CO3(144.0 mg, 1.04 mmol) and KI (60.0 mg, 0.36 mmol). The mixture was stirred at 80 °C for 4 h, cooled to rt, poured into water (10 mL) and extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4, filtered and concentrated in vacuum to give crude compound 28.1 (80.0 mg) as brown oil. MS [M+H]+: 426.2. Step 2: 5-[4-[3-(3-methylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxylic acid (compound 28.2) To an 8 mL vial were added compound 28.1 (80.0 mg, 0.19 mmol) and methanol (1 mL), LiOH•H2O (41.0 mg, 0.98 mmol) and water (0.2 mL). The mixture was stirred at 25 °C for 2 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed- phase chromatography to give compound 28.2 (40.0 mg) as pink solid. MS [M+H]+: 412.2. Step 3: 5-[4-[3-(3-methylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide (Example 28) To an 8 mL vial were added compound 28.2 (40.0 mg, 0.1 mmol), DMF (1 mL), NH4Cl (28.0 mg, 0.53 mmol), HATU (77.0 mg, 0.2 mmol) and DIEA (28.0 mg, 0.22 mmol). The mixture was stirred at 20 °C for 2 h and filtered. The filtrate was concentrated in vacuum. The crude product was purified by reversed-phase chromatography to give Example 28 (18.2 mg) as white solid. MS [M+H]+: 411.2.1H NMR (400 MHz, METHANOL-d4) δ ppm 8.57 (s, 1 H), 8.40 (s, 1 H), 7.91 (s, 1 H), 7.68 (s, 1 H), 7.22 - 7.32 (m, 2 H), 6.98 - 7.12 (m, 2 H), 6.18 (d, J = 1.2Hz, 1 H), 4.14 (t, J = 5.6Hz, 2 H), 3.76 - 3.99 (m, 3 H), 3.51 (dd, J = 12.4, 8.8Hz, 1 H), 3.32 - 3.44 (m, 2 H), 3.10 - 3.23 (m, 1 H), 2.89 - 3.08 (m, 2 H), 2.00 - 2.32 (m, 2 H), 1.26 (d, J = 6.4 Hz, 3 H). Example 29 5-[4-[3-(3-ethylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-[3-(3-ethylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Example 29) was prepared in analogy to Example 28, by replacing 3-methylmorpholine with 3-ethylmorpholine in step 1. MS [M+H]+: 425.3 MS [M+H]+.1H NMR (400 MHz, DMSO-d6) δ ppm 8.59 (s, 1 H), 8.13 (s, 1 H), 8.02 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.38 (br s, 1 H), 7.34 (d, J = 9.2Hz, 2 H), 7.07 (d, J = 9.2Hz, 2 H), 6.06 (d, J = 1.2Hz, 1 H), 4.08 (br t, J = 6.0Hz, 2 H), 3.65 - 3.81 (m, 2 H), 3.47 - 3.62 (m, 2 H), 2.87 - 3.13 (m, 2 H), 2.52 (br s, 3 H), 1.85 - 2.05 (m, 2 H), 1.35 - 1.68 (m, 2 H), 0.84 (br t, J = 7.2Hz, 3 H). Example 30 1-methyl-7-[4-[2-(2-oxooxazolidin-3-yl)ethoxy]phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-5a and 3-(2-chloroethyl)oxazolidin-2-one according to the following scheme: To a solution of Int-5a (40.0 mg, 0.14 mmol) in ACN (3 mL) was added 3-(2- chloroethyl)oxazolidin-2-one (63.4 mg, 0.42 mmol) and K2CO3 (58.6 mg, 0.42 mmol). The mixture was stirred at 90 °C for 12 h, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 30 (5.4 mg) as white solid. MS [M+H]+: 397.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (s, 1 H), 7.96 (br s, 1 H), 7.27 (br s, 1 H), 7.17 (s, 1 H), 7.12 (d, J = 8.8Hz, 2 H), 7.04 (d, J = 8.8Hz, 2 H), 4.27 (t, J = 8.0Hz, 2 H), 4.21 (s, 3 H), 4.14 (t, J = 5.2Hz, 2 H), 3.67 (t, J = 8.0Hz, 2 H), 3.55 (t, J = 5.2Hz, 2 H). Example 31 5-[4-[3-(3,3-dimethylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide The titled compound was synthesized from Int-6c and 3,3-dimethylmorpholine according to the following scheme: To an 8 mL vial were added Int-6c (50.0 mg, 0.14 mmol), DMF (1 mL), 3,3- dimethylmorpholine (118.8 mg, 1.03 mmol), K2CO3 (62.6 mg, 0.45 mmol) and KI (26.0 mg, 0.16 mmol). The mixture was stirred at 80 °C for 12 h, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 31 (30.7 mg) as white solid. MS [M+H]+: 425.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.59 (s, 1 H), 8.13 (s, 1 H), 8.03 (s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.40 (s, 1 H), 7.33 (d, J = 8.8Hz, 2 H), 7.08 (d, J = 9.2Hz, 2 H), 6.06 (s, 1 H), 3.98 - 4.19 (m, 2 H), 3.53 - 3.78 (m, 2 H), 3.13 - 3.32 (m, 4 H), 2.52 (s, 2 H), 1.69 - 2.01 (m, 2 H), 0.78 - 1.25 (m, 6 H). Example 32 5-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Example 32) was prepared in analogy to Example 31, by replacing 3,3-dimethylmorpholine with pyrrolidin-2-one in step 1. MS [M+H]+: 395.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.58 (s, 1 H), 8.01 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.37 (br s, 1 H), 7.30 - 7.35 (m, 2 H), 7.03 - 7.10 (m, 2 H), 6.08 (d, J = 1.2Hz, 1 H), 4.01 (t, J = 6.0Hz, 2 H), 3.35 (br s, 4 H), 2.21 (t, J = 8.0Hz, 2 H), 1.94 (q, J = 6.8Hz, 4 H). Example 33 5-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Example 33) was prepared in analogy to Example 31, by replacing 3,3-dimethylmorpholine with morpholin-3-one in step 1. MS [M+H]+: 411.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.60 (s, 1 H), 8.03 (br s, 1 H), 7.95 (s, 1 H), 7.70 (s, 1 H), 7.39 (br s, 1 H), 7.33 (br d, J = 9.2Hz, 2 H), 7.07 (br d, J = 9.2Hz, 2 H), 6.07 (s, 1 H), 4.03 - 4.07 (m, 2 H), 4.01 - 4.03 (m, 2 H), 3.83 (br t, J = 5.2Hz, 2 H), 3.48 - 3.54 (m, 4 H), 1.99 (m, 2 H). Example 34 5-[4-[3-(6-oxo-2-oxa-7-azaspiro[3.4]octan-7-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide 5-[4-[3-(6-oxo-2-oxa-7-azaspiro[3.4]octan-7-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine- 7-carboxamide (Example 34) was prepared in analogy to Example 31, by replacing 3,3- dimethylmorpholine with 2-oxa-7-azaspiro[3.4]octan-6-one in step 1. MS [M+H]+: 437.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.58 (s, 1 H), 8.01 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.37 (br s, 1 H), 7.30 - 7.35 (m, 2 H), 7.03 - 7.09 (m, 2 H), 6.08 (d, J = 1.2Hz, 1 H), 4.53 (s, 4 H), 3.93 - 4.04 (m, 2 H), 3.67 (s, 2 H), 3.35 (br s, 2 H), 2.63 (s, 2 H), 1.93 (br t, J = 6.4Hz, 2 H). Example 36 7-[4-[3-(2-benzyloxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5-carboxamide The titled compound was synthesized from Int-6a and Int-10a according to the following scheme: Step 1: methyl 7-(4-bromophenoxy)-1-methyl-indazole-5-carboxylate (compound 36.1) To a solution of methyl 7-bromo-1-methyl-indazole-5-carboxylate (500.0 mg, 1.86 mmol) in DMF (10 mL) were added CuI (177.0 mg, 0.93 mmol), K2CO3 (770.4 mg, 5.57 mmol), 4- bromophenol (643.0 mg, 3.72 mmol) and BPPO (received from Accela ChemBio; 364.6 mg, 0.93 mmol). The suspension was degassed and purged with N2 three times and stirred at 90 °C for 12 h under N2. The mixture was cooled to rt and filtrated. The filtrate was diluted with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtrated and concentrated in vacuum. The residue was purified by reversed-phase chromatography to give compound 36.1 (160.0 mg) as white solid. MS [M+H]+: 361.0. Step 2: methyl 7-[4-[3-(2-benzyloxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5- carboxylate (compound 36.2) To a solution of compound 36.1 (140.0 mg, 0.39 mmol) in 1,4-dioxane (5 mL) were added Int-10a (80.0 mg, 0.39 mmol), Cs2CO3(378.9 mg, 1.16 mmol) andtBuXPhos Pd G3 (Sigma- Aldrich; 30.8 mg, 0.04 mmol). The suspension was degassed and purged with N2three times and stirred at 110 °C for 12 h under N2. The mixture was cooled and concentrated in vacuum. The residue was diluted with water (20 mL) and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, filtrated and concentrated in vacuum. The residue was purified by prep-TLC to give compound 36.2 (70.0 mg) as yellow oil. MS [M+H]+: 488.3. Step 3: 7-[4-[3-(2-benzyloxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5-carboxylic acid (compound 36.3) To a 100 mL flask were added compound 36.2 (70.0 mg, 0.14 mmol), methanol (3 mL), H2O (1 mL) and LiOH•H2O (24.1 mg, 0.57 mmol). The mixture was stirred at 20 °C for 12 h, adjusted to pH = 5-7 with 1 M HCl aqueous solution and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4and filtrated. The filtrate was concentrated in vacuum to give compound 36.3 (50.0 mg) as white solid. MS [M+H]+: 474.2. Step4: 7-[4-[3-(2-benzyloxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5- carboxamide (Example 36) To a 40 mL vial were added compound 36.3 (50.0 mg, 0.11 mmol), HATU (80.0 mg, 0.21 mmol), DIEA (27.3 mg, 0.21 mmol), NH4Cl (28.3 mg, 0.53 mmo) and DMF (5 mL). The mixture was stirred at 20 °C for 2 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 36 (23.2 mg) as white solid. MS [M+H]+: 473.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.18 (s, 1 H), 8.01 (d, J = 1.2Hz, 1 H), 7.94 (br s, 1 H), 7.37 - 7.32 (m, 4 H), 7.31 - 7.22 (m, 2 H), 7.10 (d, J = 1.0Hz, 1 H), 7.04 (d, J = 9.0Hz, 2 H), 6.51 (d, J = 9.0Hz, 2 H), 4.51 (s, 2 H), 4.47 - 4.40 (m, 1 H), 4.23 (s, 3 H), 4.06 (t, J = 7.1Hz, 2 H), 3.63 - 3.60 (m, 2 H), 3.59 (s, 4 H). Example 37 7-[4-[3-(2-hydroxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5-carboxamide The titled compound was synthesized from Example 36 according to the following scheme: Example 36Example 37 To a suspension of Pd / C (20 mg, 10 % loading) in methanol (10 mL) was added Example 36 (20.0 mg, 0.04 mmol) under N2. The suspension was degassed and purged with H2three times and stirred under H2 balloon at 30 °C for 24 h. The resulting mixture was filtered. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 37 (7.3 mg) as white solid. MS [M+H]+: 383.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.17 (s, 1 H), 8.01 (d, J = 1.2Hz, 1 H), 7.93 (s, 1 H), 7.25 (s, 1 H), 7.10 (d, J = 1.2Hz, 1 H), 7.03 (d, J = 8.8Hz, 2 H), 6.52 (d, J = 8.8Hz, 2 H), 4.67 (t, J = 2.8Hz, 1 H), 4.48 - 4.40 (m, 1 H), 4.23 (s, 3 H), 4.07 (t, J = 6.0Hz, 2 H), 3.64 - 3.59 (m, 2 H), 3.55 - 3.49 (m, 2 H), 3.43 (d, J = 4.8Hz, 2 H). Example 38 7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1H-indazole-5-carboxamide 7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1H-indazole-5-carboxamide (Example 38) was prepared in analogy to Example 2, by replacing Int-1a and tert-butyl 4-(2- hydroxyethoxy)piperidine-1-carboxylate with Int-1e and Int-7b in step 1; HCl with TFA in step 4. MS [M+H]+:398.1.1H NMR (400 MHz, DMSO-d6) δ ppm 13.70 (s, 1H), 8.23 (s, 1H), 8.06 (s, 1H), 7.94 (br s, 1H), 7.23 (br s, 1H), 7.13 (br d, J = 8.8 Hz, 2H), 7.09 (s, 1H), 7.03 (br d, J = 8.8 Hz, 2H), 4.15 - 4.06 (m, 2H), 3.86 - 3.80 (m, 2H), 3.77 (br dd, J = 9.2, 4.2 Hz, 3H), 3.71 - 3.63 (m, 2H), 1.92 - 1.81 (m, 2H), 1.46 - 1.31 (m, 2H). Example 39 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-1e and Int-7b according to the following scheme: Step 1: methyl 7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-(2- trimethylsilylethoxymethyl)indazole-5-carboxylate (compound 39.1) A mixture of Int-1e (110.0 mg, 0.27 mmol), Int-7b (77.0 mg, 0.53 mmol) and CMPA (187.0 mg, 0.77 mmol) in toluene (5 mL) was degassed and backfilled with N2 for three times. The mixture was stirred at 80 °C for 2 h under N2, cooled to rt and concentrated in vacuum. The residue was purified by prep. HPLC to give compound 39.1 (30.0 mg) as brown oil and 80 mg of recovered Int-1e. MS [M+H]+: 543.2. Step 2: methyl 7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1H-indazole-5-carboxylate (compound 39.2) A solution of compound 39.1 (120.0 mg, 0.22 mmol) and TFA (2.5 mL) in DCM (10.0 mL) was stirred at 20 °C for 15 h. The mixture was concentrated in vacuum, diluted with water (30 mL) and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum to give compound 39.2 (0.1 g) as yellow solid, which was used in the next step directly without further purification. MS [M+H]+: 413.1. Step 3: methyl 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxylate (compound 39.3) A mixture of cesium carbonate (126.0 mg, 0.39 mmol), iodomethane (28.0 mg, 0.2 mmol) and compound 39.2 (80.0 mg, 0.19 mmol) in DMF (3.0 mL) was stirred at 20 °C for 4 h. The mixture was diluted with EtOAc, washed with water and brine successively, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to give compound 39.3 (70.0 mg) as light yellow solid. MS [M+H]+: 427.2. Step 4: 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxylic acid (compound 39.4) A mixture of compound 39.3 (50.0 mg, 0.12 mmol) and LiOH•H2O (20.0 mg, 0.48 mmol) in water (0.5 mL) and THF (2.5 mL) was stirred at 20 °C for 3 h. The mixture was diluted with water (3 mL), concentrated in vacuum and adjusted to pH = 5-6 with 1 M HCl(aq.). The aqueous phase was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum to give compound 39.4 (48.0 mg) as light yellow solid. MS [M+H]+: 413.1. Step 5: 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide (Example 39) To the solution of compound 39.4 (45.0 mg, 0.11 mmol) in DMF (2.0 mL) were added HATU (45.0 mg, 0.12 mmol) and DIEA (28.0 mg, 0.22 mmol) at 0 °C. The mixture was stirred at 0 °C for 0.1 h. To the mixture was added NH4Cl (27.0 mg, 0.5 mmol) at 0 °C. The resulting mixture was stirred for 0.9 h and purified directly by prep. HPLC to give Example 39 (10.6 mg) as white solid. MS [M+H]+: 412.2.1H NMR (400 MHz, MeOD): δ ppm 8.11 (s, 1 H), 8.03 (s, 1 H), 7.22 (s, 1 H), 7.05 - 7.12 (m, 2 H), 6.98 - 7.05 (m, 2 H), 4.28 (s, 3 H), 4.10 - 4.17 (m, 2 H), 3.88 - 3.96 (m, 2 H), 3.81 - 3.87 (m, 2 H), 3.60 - 3.70 (m, 1 H), 3.41 - 3.53 (m, 2 H), 1.89 - 2.01 (m, 2 H), 1.52 - 1.64 (m, 2 H). Example 41 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carbonitrile The titled compound was synthesized from Example 10 according to the following scheme: To a solution of Example 10 (82.4 mg, 0.20 mmol) in THF (4.0 mL) were added TFAA (102 mg, 0.48 mmol) and TEA (122 mg, 1.20 mmol) at 0 °C. The mixture was stirred at rt for 1 h and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 41 (38 mg) as white solid. MS [M+H]+: 394.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.25 (s, 1H), 8.07 (d, J = 0.8 Hz, 1H), 7.15 - 7.10 (m, 2H), 7.09 - 7.05 (m, 2H), 6.81 (s, 1H), 4.16 (dd, J = 3.9, 5.5 Hz, 2H), 3.99 - 3.86 (m, 7H), 3.72 - 3.62 (m, 1H), 3.48 (ddd, J = 2.8, 9.4, 11.8 Hz, 2H), 1.99 - 1.92 (m, 2H), 1.63 - 1.54 (m, 2H). Example 42 1-[1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5-yl]ethanone The titled compound was synthesized from Int-1b and Int-8a according to the following scheme: Example 42Step 1: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxylate (compound 42.1) To a solution of Int-1b (322.0 mg, 1.08 mmol) and Int-8a (649.0 mg, 2.16 mmol) in ACN (10 mL) was added K2CO3 (299 mg, 2.16 mmol). The mixture was stirred at 80 °C for 16 h, cooled to rt and filtered. The filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give compound 42.1 (351.4 mg). MS [M+H]+: 427.1. Step 2: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxylic acid (compound 42.2) To an 8 mL vial were added compound 42.1 (30.0 mg, 0.07 mmol), methanol (1 mL), LiOH•H2O (6.0 mg, 0.14 mmol) and water (0.2 mL). The mixture was stirred at 50 °C for 2 h, cooled to rt and adjusted to pH = 5-7 with 1 M HCl(aq.). The aqueous phase was extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum to give compound 42.2 (25.0 mg) which was used directly in the next step without further purification. MS [M+H]+: 413.1. Step 3: N-methoxy-N,1-dimethyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole- 5-carboxamide (compound 42.3) To an 8 mL vial were added compound 42.2 (30.0 mg, 0.07 mmol), HATU (42.0 mg, 0.11 mmol), N-methoxymethanamine hydrochloride (22.0 mg, 0.22 mmol) and DIEA (48 mg, 0.37 mmol) in DMF (0.6 mL). The mixture was stirred at 20 °C for 2 h, quenched with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4, filtrated and concentrated in vacuum. The residue was purified by flash chromatography to give compound 42.3 (28.0 mg). MS [M+H]+: 456.2. Step 4: 1-[1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5-yl]ethanone (Example 42) To a solution of compound 42.3 (121.6 mg, 0.27 mmol) in dry THF (3 mL) was added dropwise MeLi (3.1 M, 0.14 mL, 0.43 mmol) at -78 °C. The resulting solution was stirred at the same temperature for 0.5 h, then warmed up to rt and stirred for 2 h. The reaction was quenched with sat. NH4Cl and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 42 (41 mg) as white solid. MS [M+H]+: 411.2.1H NMR (400 MHz, METHANOL-d4) δ = 8.24 (s, 1H), 8.07 (s, 1H), 7.06 (q, J = 9.0 Hz, 4H), 6.79 (s, 1H), 4.24 - 4.04 (m, 2H), 3.97 - 3.80 (m, 7H), 3.72 - 3.59 (m, 1H), 3.53 - 3.42 (m, 2H), 2.66 (s, 3H), 1.95 (d, J = 10.4 Hz, 2H), 1.66 - 1.50 (m, 2H). Example 43 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide The titled compound was synthesized from Int-17a according to the following scheme: To an 8 mL vial were added Int-17a (75.7 mg, 0.19 mmol), DMF (2 mL), NH4Cl (50.0 mg, 0.94 mmol), HATU (108.0 mg, 0.28 mmol) and DIEA (243.0 mg, 1.88 mmol). The resulting mixture was stirred at 20 °C for 2 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 43 (30.0 mg) as white solid. MS [M+H]+: 398.3.1H NMR (400 MHz, METHANOL-d4) δ = 8.25 (s, 1H), 8.22 (s, 1H), 7.74 (s, 1H), 7.62 (s, 1H), 7.16 - 7.10 (m, 2H), 7.07 - 6.99 (m, 2H), 4.13 (dd, J = 3.8, 5.4 Hz, 2H), 3.94 - 3.82 (m, 4H), 3.65 (tt, J = 4.2, 8.7 Hz, 1H), 3.47 (ddd, J = 2.8, 9.4, 11.8 Hz, 2H), 1.99 - 1.91 (m, 2H), 1.62 - 1.53 (m, 2H). Example 44 3-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide The titled compound was synthesized from Int-16a according to the following scheme: Step 1: methyl 2-(acetamidomethyl)-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]pyridine-4-carboxylate (compound 44.1) To a solution of Int-16a (402.4 mg, 1.00 mmol) in DCM (10 mL) were added acetyl chloride (118.0 mg, 1.5 mmol) and TEA (152.0 mg, 2 mmol) at 0 °C. The resulting solution was stirred at rt for 1 h, diluted with sat. NaHCO3at 0 °C and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The crude compound 44.1 (398.1 mg) was used in the next step without further purification. MS [M+H]+: 445.0. Step 2: methyl 3-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5- a]pyridine-7-carboxylate (compound 44.2) To a solution of compound 44.1 (444.5 mg, 1.00 mmol) in dry toluene (8 mL) was added POCl3(184.0 mg, 1.20 mmol) at 0 °C. The resulting solution was stirred at 100 °C for 1 h, cooled to rt and quenched with sat. NaHCO3 at 0 °C. The aqueous phase was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography to give compound 44.2 (218.2 mg) as brown oil. MS [M+H]+: 427.4. Step 3: 3-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine- 7-carboxylic acid (compound 44.3) To a 50 mL round-bottom flask were added compound 44.2 (178.1 mg, 0.42 mmol), methanol (8 mL), LiOH•H2O (36.0 mg, 0.84 mmol) and water (2 mL). The mixture was stirred at 50 °C for 2 h, cooled to rt and adjusted to pH = 5-7 with 1M HCl(aq.). The aqueous phase was extracted with DCM. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum to give compound 44.3 (113.8 mg) which was used directly in the next step. MS [M+H]+: 413.4. Step 4: 3-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine- 7-carboxamide (Example 44) To an 8 mL vial were added compound 44.3 (453.6 mg, 1.10 mmol), DMF (10 mL), NH4Cl (295.0 mg, 5.50 mmol), HATU (628.0 mg, 1.65 mmol) and DIEA (1.4 g, 11.0 mmol). The resulting mixture was stirred at 20 °C for 2 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 44 (208.0 mg) as white solid. MS [M+H]+: 412.2.1H NMR (500 MHz, METHANOL-d4) δ = 8.27 (s, 1H), 8.07 (s, 1H), 7.55 (s, 1H), 7.23 - 7.13 (m, 2H), 7.08 - 7.02 (m, 2H), 4.19 - 4.10 (m, 2H), 3.94 - 3.84 (m, 4H), 3.65 (tt, J = 4.1, 8.7 Hz, 1H), 3.48 (ddd, J = 2.7, 9.4, 11.8 Hz, 2H), 2.73 (s, 3H), 1.99 - 1.92 (m, 2H), 1.57 (dtd, J = 4.1, 9.1, 13.3 Hz, 2H). Example 47 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6- carboxamide The titled compound was synthesized from methyl 6-bromo-1H-indazole-5-carboxylate according to the following scheme: Step 1: methyl 6-bromo-1-ethyl-indazole-5-carboxylate (compound 47.1) To a suspension of methyl 6-bromo-1H-indazole-5-carboxylate (1.0 g, 3.92 mmol) and Cs2CO3(2.6 g, 7.84 mmol) in ACN (30 mL) was added iodoethane (734 mg, 4.70 mmol). The mixture was stirred at 20 °C for 2 h, diluted with water (30 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum. The crude was purified by flash chromatography to give compound 47.1 (657 mg) as yellow solid. MS [M+H]+: 282.9. Step 2: methyl 1-ethyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxylate (compound 47.2) A flask was dried by heating with a heat gun in vacuum. To this flask were added successively Int-9a (830.0 mg, 3.48 mmol), compound 47.1 (657.0 mg, 2.31 mmol), CuI (43.8 mg, 0.23 mmol), BMPPO (Accela ChemBio; 79.2 mg, 0.23 mmol), K3PO4(986.0 mg, 4.64 mmol) and DMSO (4 mL). The mixture was degassed and purged with N2gas for four times and stirred at 120 °C for 16 h under N2. After cooling to rt, the mixture was diluted with ethyl acetate and filtrated through kieselguhr. The filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give compound 47.2 (661.5 mg) as yellow solid. MS [M+H]+: 441.2. Step 3: 1-ethyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxylic acid (compound 47.3) To a 50 mL round-bottom flask were added compound 47.2 (661.5 mg, 1.5 mmol), methanol (10 mL), LiOH•H2O (127.0 mg, 3 mmol) and water (2 mL). The mixture was stirred at 50 °C for 2 h, cooled to rt and adjusted to pH = 5-7 with 1 M HCl(aq.). The aqueous phase was extracted with DCM. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum to give compound 47.3 (599.1 mg) which was used directly in the next step. MS [M+H]+: 427.1. Step 4: 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine- 6-carboxamide (Example 47) To a 20 mL vial were added compound 47.3 (302.8 mg, 0.71 mmol), DMF (10 mL), NH4Cl (189.0 mg, 3.52 mmol), HATU (405.0 mg, 1.07 mmol) and DIEA (918 mg, 7.10 mmol). The resulting mixture was stirred at 20 °C for 2 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 44 (190.0 mg) as white solid. MS [M+H]+: 426.2.1H NMR (500 MHz, METHANOL-d4) δ = 8.32 (s, 1H), 7.98 (d, J = 0.8 Hz, 1H), 7.03 - 7.01 (m, 2H), 6.96 - 6.94 (m, 2H), 6.69 (s, 1H), 4.15 (q, J = 7.2 Hz, 2H), 4.05 (dd, J = 3.9, 5.4 Hz, 2H), 3.85 - 3.73 (m, 4H), 3.61 - 3.51 (m, 1H), 3.42 - 3.31 (m, 2H), 1.89 - 1.83 (m, 2H), 1.55 - 1.44 (m, 2H), 1.24 (t, J = 7.2 Hz, 3H). Example 48 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyrazolo[4,3-b]pyridine-5- carbonitrile The titled compound was synthesized from 6-bromo-1H-pyrazolo[4,3-b]pyridine according to the following scheme: Step 1: 6-bromo-1-methyl-pyrazolo[4,3-b]pyridine (compound 48.1) To a suspension of 6-bromo-1H-pyrazolo[4,3-b]pyridine (6.0 g, 30.30 mmol) and Cs2CO3(20.0 g, 60.6 mmol) in ACN (60 mL) was added iodomethane (5.2 g, 36.36 mmol). The mixture was stirred at 20 °C for 2 h, diluted with water (30 mL) and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified by flash chromatography to give compound 48.1 (3.44 g) as yellow solid. MS [M+H]+: 211.9. Step 2: 6-bromo-1-methyl-4-oxido-pyrazolo[4,3-b]pyridin-4-ium (compound 48.2) To a solution of compound 48.1 (2.0 g, 9.43 mmol) in DCM (40 mL) was added m-CPBA (2.0 g, 113.2 mmol). The mixture was stirred at 20 °C for 16 h, adjusted to pH = 9-10 with 4 M NaOH(aq.) and extracted with DCM. The combined organic extract was dried over Na2SO4 and concentrated in vacuum to give crude compound 48.2 (1.95 g) which was used in the next step without purification. MS [M+H]+: 227.9. Step 3: 6-bromo-1-methyl-pyrazolo[4,3-b]pyridine-5-carbonitrile (compound 48.3) To a solution of compound 48.2 (1.9 g, 8.34 mmol) in ACN (40 mL) were added trimethylsilyl cyanide (1.2 g, 12.50 mmol) and TEA (1.7 g, 16.68 mmol). The mixture was stirred at 110 °C for 16 h, cooled to rt and concentrated in vacuum. The residue was purified by flash chromatography to give compound 48.3 (1.7 g) as yellow solid. MS [M+H]+: 236.9. Step 4: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyrazolo[4,3-b]pyridine- 5-carbonitrile (Example 48) A flask was dried by heating with a heat gun in vacuum. To this flask were added successively Int-9a (1.2 g, 4.87 mmol), compound 48.3 (962.0 mg, 4.05 mmol), CuI (78.1 mg, 0.41 mmol), BMPPO (Accela ChemBio; 141.2 mg, 0.41 mmol), K3PO4(1.8 g, 8.1 mmol) and DMSO (6 mL). The mixture was degassed and purged with N2 gas for four times, and stirred at 120 °C for 16 h under N2. After cooling to rt, the mixture was diluted with ethyl acetate and filtrated through kieselguhr. The filtrate was concentrated in vacuum. The residue was purified by prep. HPLC to give Example 48 (448.3 mg) as white solid. MS [M+H]+: 395.1.1H NMR (500 MHz, METHANOL-d4) δ = 8.15 (d, J = 0.8 Hz, 1H), 7.25 (d, J = 0.9 Hz, 1H), 7.09 - 7.07 (m, 2H), 7.00 - 6.96 (m, 2H), 4.07 (dd, J = 3.9, 5.4 Hz, 2H), 3.86 - 3.76 (m, 7H), 3.66 - 3.47 (m, 1H), 3.41 - 3.34 (m, 2H), 1.89 - 1.82 (m, 2H), 1.52 - 1.34 (m, 2H). Example 49 1-methyl-6-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-4a according to the following scheme: To a solution of Int-4a (200.0 mg, 0.71 mmol) and Int-8g (404 mg, 1.42 mmol) in DMF (3 mL) was added K2CO3(293.0 mg, 2.11 mmol). The mixture was stirred at 80 °C for 16 h, cooled to rt and filtered through a pad of Celite. The cake was washed with DCM. The filtrate was concentrated in vacuum. The residue was purified by prep. HPLC to give Example 49 (121.0 mg) as white solid. MS [M+H]+: 398.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.44 (s, 1H), 8.08 (s, 1H), 7.17 - 7.10 (m, 2H), 7.09 - 7.03 (m, 2H), 6.79 (s, 1H), 4.35 - 4.25 (m, 1H), 4.16 (t, J = 4.6 Hz, 2H), 3.91 - 3.79 (m, 9H), 2.10 - 2.04 (m, 2H). Example 50 and Example 51 1-methyl-6-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide and 1-methyl-6-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5- carboxamide 1-methyl-6-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide and 1-methyl-6-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide (Example 50 and Example 51) were prepared in analogy to Example 4 and Example 5 by SFC. Example 50 (5.1 mg), faster fraction, white solid. MS [M+H]+: 398.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.32 (s, 1H), 7.96 (s, 1H), 7.05 - 6.99 (m, 2H), 6.97 - 6.92 (m, 2H), 6.67 (s, 1H), 4.21 - 4.15 (m, 1H), 4.04 (t, J = 4.6 Hz, 2H), 3.81 - 3.67 (m, 9H), 1.98 - 1.92 (m, 2H). Example 51 (6.3 mg), slower fraction, white solid. MS [M+H]+: 398.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.32 (s, 1H), 7.97 (d, J = 0.8 Hz, 1H), 7.05 - 6.99 (m, 2H), 6.97 - 6.92 (m, 2H), 6.67 (s, 1H), 4.21 - 4.15 (m, 1H), 4.04 (t, J = 4.6 Hz, 2H), 3.81 - 3.67 (m, 9H), 1.98 - 1.92 (m, 2H). Example 52 6-[4-[2-(cyclopropoxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-[2-(cyclopropoxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide (Example 52) was prepared in analogy to Example 49, by replacing Int-8g with 2-(cyclopropoxy)ethyl 4- methylbenzenesulfonate in step 1. MS [M+H]+: 368.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.44 (s, 1H), 8.08 (s, 1H), 7.18 - 7.10 (m, 2H), 7.09 - 7.03 (m, 2H), 6.79 (s, 1H), 4.15 (dd, J = 3.8, 5.4 Hz, 2H), 3.92 - 3.87 (m, 5H), 3.50 - 3.41 (m, 1H), 0.63 - 0.50 (m, 4H). Example 53 1-methyl-6-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide 1-methyl-6-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide (Example 53) was prepared in analogy to Example 49, by replacing Int-8g with 4-(3-bromopropyl)morpholine; hydrobromide in step 1. MS [M+H]+: 411.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.30 (s, 1H), 7.97 (s, 1H), 7.05 - 7.00 (m, J = 9.0 Hz, 2H), 6.98 - 6.91 (m, J = 9.0 Hz, 2H), 6.68 (s, 1H), 4.05 (t, J = 5.6 Hz, 2H), 3.84 (br s, 3H), 3.78 (s, 3H), 3.27 - 3.17 (m, 7H), 2.25 - 2.09 (m, 2H). Example 56 1-methyl-6-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-6-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide (Example 56) was prepared in analogy to Example 49, by replacing Int-8g with 4-(3- bromopropyl)morpholin-3-one in step 1. MS [M+H]+: 425.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.32 (s, 1H), 7.97 (d, J = 0.8 Hz, 1H), 7.04 - 6.99 (m, 2H), 6.97 - 6.90 (m, 2H), 6.67 (s, 1H), 4.02 - 3.95 (m, 4H), 3.82 - 3.78 (m, 2H), 3.78 (s, 3H), 3.53 (t, J = 7.1 Hz, 2H), 3.38 (t, J = 5.1 Hz, 2H), 2.00 (m, 2H). Example 57 6-[4-(3-methoxy-3-methyl-butoxy)phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-(3-methoxy-3-methyl-butoxy)phenoxy]-1-methyl-indazole-5-carboxamide (Example 57) was prepared in analogy to Example 49, by replacing Int-8g with Int-8i in step 1. MS [M+H]+: 384.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.44 (s, 1H), 8.08 (d, J = 0.8 Hz, 1H), 7.18 - 7.08 (m, 2H), 7.06 - 7.00 (m, 2H), 6.79 (s, 1H), 4.11 (t, J = 6.9 Hz, 2H), 3.89 (s, 3H), 3.26 (s, 3H), 2.04 (t, J = 6.9 Hz, 2H), 1.28 (s, 6H). Example 58 1-methyl-6-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-6-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide (Example 58) was prepared in analogy to Example 49, by replacing Int-8g with Int-8f in step 1. MS [M+H]+: 409.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.60 (br s, 1H), 7.48 (br s, 1H), 7.11 - 7.02 (m, 2H), 7.00 - 6.94 (m, 2H), 6.92 (s, 1H), 3.96 (t, J = 6.2 Hz, 2H), 3.89 (s, 3H), 3.41 - 3.34 (m, 4H), 2.24 - 2.17 (m, 2H), 1.97 - 1.87 (m, 4H). Example 59 1-methyl-6-[4-[3-(2-methyl-5-oxo-pyrrolidin-1-yl)propoxy]phenoxy]indazole-5- carboxamide 1-methyl-6-[4-[3-(2-methyl-5-oxo-pyrrolidin-1-yl)propoxy]phenoxy]indazole-5- carboxamide (Example 59) was prepared in analogy to Example 49, by replacing Int-8g with Int-19a in step 1. MS [M+H]+: 423.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.61 (br s, 1H), 7.47 (br s, 1H), 7.09 - 7.03 (m, 2H), 7.00 - 6.95 (m, 2H), 6.95 - 6.85 (m, 1H), 3.96 (t, J = 6.3 Hz, 2H), 3.88 (s, 3H), 3.69 (qd, J = 6.2, 12.7 Hz, 1H), 3.62 - 3.42 (m, 1H), 3.10 - 3.03 (m, 1H), 2.29 - 2.08 (m, 3H), 2.04 - 1.76 (m, 2H), 1.64 - 1.36 (m, 1H), 1.16 (d, J = 6.3 Hz, 3H). Example 60 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropoxy)phenoxy]indazole-5-carboxamide 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropoxy)phenoxy]indazole-5-carboxamide (Example 60) was prepared in analogy to Example 49, by replacing Int-8g with Int-8j in step 1. MS [M+H]+: 426.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.61 (br s, 1H), 7.54 - 7.41 (m, 1H), 7.12 - 7.03 (m, 2H), 7.02 - 6.95 (m, 2H), 6.91 (s, 1H), 4.03 (t, J = 6.3 Hz, 2H), 3.88 (s, 3H), 3.78 (td, J = 4.3, 11.5 Hz, 2H), 3.58 (t, J = 6.3 Hz, 2H), 3.52 - 3.44 (m, 1H), 3.36 - 3.29 (m, 2H), 1.94 (quin, J = 6.3 Hz, 2H), 1.88 - 1.78 (m, 2H), 1.38 (dtd, J = 4.1, 9.3, 13.2 Hz, 2H). Example 61 and Example 62 1-methyl-6-[4-[2-[rac-(3R,4R)-3-methyltetrahydropyran-4-yl]oxyethoxy]phenoxy]indazole- 5-carboxamide and 1-methyl-6-[4-[2-[rac-(3S,4R)-3-methyltetrahydropyran-4- yl]oxyethoxy]phenoxy]indazole-5-carboxamide 1-methyl-6-[4-[2-[rac-(3R,4R)-3-methyltetrahydropyran-4-yl]oxyethoxy]phenoxy]indazole- 5-carboxamide and 1-methyl-6-[4-[2-[rac-(3S,4R)-3-methyltetrahydropyran-4- yl]oxyethoxy]phenoxy]indazole-5-carboxamide (Example 61 and Example 62) were prepared in analogy to Example 49, by replacing Int-8g with Int-8k and Int-8l in step 1. Example 61, slower fraction, white solid. MS [M+H]+: 426.3.1H NMR (400 MHz, DMSO-d6) δ = 8.19 (s, 1H), 8.10 (s, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.10 - 7.03 (m, 2H), 7.03 - 6.97 (m, 2H), 6.90 (s, 1H), 4.15 - 4.03 (m, 2H), 3.92 - 3.83 (m, 5H), 3.76 - 3.63 (m, 2H), 3.37 - 3.25 (m, 1H), 3.11 (dt, J = 4.3, 9.7 Hz, 1H), 2.95 (t, J = 10.9 Hz, 1H), 2.05 - 1.95 (m, 1H), 1.62 - 1.48 (m, 1H), 1.41 - 1.26 (m, 1H), 0.85 (d, J = 6.6 Hz, 3H). Example 62, faster fraction, white solid. MS [M+H]+: 426.3.1H NMR (400 MHz, DMSO-d6) δ = 8.19 (s, 1H), 8.10 (s, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.09 - 7.04 (m, 2H), 7.03 - 6.98 (m, 2H), 6.90 (s, 1H), 4.20 - 4.02 (m, 2H), 3.90 - 3.82 (m, 3H), 3.80 - 3.56 (m, 4H), 3.46 - 3.23 (m, 3H), 2.02 - 1.86 (m, 1H), 1.75 - 1.50 (m, 2H), 0.86 (d, J = 7.0 Hz, 3H). Example 63 1-methyl-6-[4-(2-methyl-3-tetrahydropyran-4-yloxy-propoxy)phenoxy]indazole-5- carboxamide 1-methyl-6-[4-(2-methyl-3-tetrahydropyran-4-yloxy-propoxy)phenoxy]indazole-5- carboxamide (Example 63) was prepared in analogy to Example 49, by replacing Int-8g with Int-20a in step 1. MS [M+H]+: 440.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.60 (br s, 1H), 7.48 (br s, 1H), 7.08 - 7.03 (m, 2H), 7.02 - 6.96 (m, 2H), 6.91 (s, 1H), 3.95 - 3.91 (m, 1H), 3.88 (s, 3H), 3.86 - 3.82 (m, 1H), 3.79 - 3.74 (m, 2H), 3.49 - 3.34 (m, 4H), 3.31 - 3.30 (m, 1H), 2.18 - 2.06 (m, 1H), 1.86 - 1.78 (m, 2H), 1.44 - 1.34 (m, 2H), 1.01 (d, J = 6.9 Hz, 3H). Example 67 6-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 67) was prepared in analogy to Example 47, by replacing iodoethane with iodomethane in step 1; Int-9a with Int-21a in step 2. MS [M+H]+: 427.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.62 (br s, 1H), 7.51 (br s, 1H), 7.23 (t, J = 9.3 Hz, 1H), 7.06 (dd, J = 2.9, 12.6 Hz, 1H), 6.86 - 6.81 (m, 2H), 4.00 (t, J = 6.2 Hz, 2H), 3.88 (s, 3H), 3.38 - 3.32 (m, 4H), 2.25 - 2.17 (m, 2H), 1.98 - 1.87 (m, 4H). Example 68 1-methyl-6-[4-(3-morpholino-3-oxo-propoxy)phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-22a according to the following scheme: To a 20 mL vial were added Int-22a (580.0 mg, 1.63 mmol), DMF (10 mL), morpholine (214.0 mg, 2.45 mmol), HATU (932.0 mg, 2.45 mmol) and DIEA (632.0 mg, 4.89 mmol). The resulting mixture was stirred at 20 °C for 2 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 68 (170.0 mg) as white solid. MS [M+H]+: 425.2.1H NMR (500 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (s, 1H), 7.62 (br s, 1H), 7.49 (br s, 1H), 7.11 - 7.03 (m, 2H), 7.01 - 6.96 (m, 2H), 6.91 (s, 1H), 4.20 (t, J = 6.2 Hz, 2H), 3.89 (s, 3H), 3.61 - 3.43 (m, 8H), 2.82 (t, J = 6.2 Hz, 2H). Example 69 6-[2-fluoro-4-[3-oxo-3-(3-oxopiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide 6-[2-fluoro-4-[3-oxo-3-(3-oxopiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 69) was prepared in analogy to Example 68, by replacing morpholine and Int-22a with piperazin-2-one and Int-22b in step 1. MS [M+H]+: 456.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (s, 1H), 7.62 (br s, 1H), 7.51 (br s, 1H), 7.23 (t, J = 9.3 Hz, 1H), 7.12 - 7.01 (m, 1H), 6.88 - 6.78 (m, 2H), 4.28 - 4.20 (m, 2H), 4.18 - 4.05 (m, 1H), 4.01 - 3.92 (m, 1H), 3.88 (s, 3H), 3.73 - 3.59 (m, 2H), 3.22 - 3.17 (m, 1H), 3.12 - 2.97 (m, 1H), 2.86 (td, J = 5.8, 18.8 Hz, 2H). Example 70 6-[2-fluoro-4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide 6-[2-fluoro-4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 70) was prepared in analogy to Example 68, by replacing morpholine and Int-22a with piperidin-4-ol hydrochloride and Int-22b in step 1. MS [M+H]+: 457.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 1.0 Hz, 1H), 7.62 (br s, 1H), 7.51 (br s, 1H), 7.23 (t, J = 9.3 Hz, 1H), 7.06 (dd, J = 2.9, 12.6 Hz, 1H), 6.84 - 6.82 (m, 2H), 4.75 (br d, J = 3.8 Hz, 1H), 4.29 - 4.21 (m, 2H), 3.96 - 3.90 (m, 1H), 3.88 (s, 3H), 3.77 - 3.60 (m, 2H), 3.27 - 3.10 (m, 2H), 3.03 (ddd, J = 3.3, 9.7, 12.9 Hz, 1H), 2.83 - 2.80 (m, 1H), 1.79 - 1.65 (m, 2H), 1.47 - 1.20 (m, 2H). Example 71 1-methyl-6-[4-(2-tetrahydropyran-3-yloxyethoxy)phenoxy]indazole-5-carboxamide 1-methyl-6-[4-(2-tetrahydropyran-3-yloxyethoxy)phenoxy]indazole-5-carboxamide (Example 71) was prepared in analogy to Example 49, by replacing Int-8g with Int-8m in step 1. MS [M+H]+: 412.1.1H NMR (400 MHz, DMSO-d6 ) δ =1.37 - 1.54 (m, 2 H), 1.61 - 1.79 (m, 1 H), 1.91 - 2.04 (m, 1 H), 3.22 (dd, J = 11.07, 7.57 Hz, 1 H), 3.29 - 3.39 (m, 2 H), 3.61 (dt, J = 11.07, 3.97 Hz, 1 H), 3.70 - 3.83 (m, 3 H), 3.88 (s, 3 H), 4.07 (t, J = 4.69 Hz, 2 H), 6.90 (s, 1 H), 6.97 - 7.02 (m, 2 H), 7.03 - 7.11 (m, 2 H), 7.48 (br s, 1 H), 7.61 (br s, 1 H), 8.10 (d, J = 0.88 Hz, 1 H), 8.18 (s, 1 H). Example 72 and Example 73 1-methyl-6-[4-[2-[(3S)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide and 1-methyl-6-[4-[2-[(3R)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5- carboxamide 1-methyl-6-[4-[2-[(3S)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide and 1-methyl-6-[4-[2-[(3R)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide (Example 72 and Example 73) were prepared in analogy to Example 4 and Example 5 by SFC. Example 72 (44 mg), faster fraction, white solid. MS [M+H]+: 412.1.1H NMR (400 MHz, DMSO-d6) δ = 1.36 - 1.57 (m, 2 H), 1.62 - 1.77 (m, 1 H), 1.91 - 2.04 (m, 1 H), 3.22 (dd, J = 11.07, 7.57 Hz, 1 H), 3.33 - 3.47 (m, 2 H), 3.61 (dt, J = 11.01, 4.06 Hz, 1 H), 3.72 - 3.83 (m, 3 H), 3.88 (s, 3 H), 4.07 (t, J = 4.75 Hz, 2 H), 6.90 (s, 1 H), 6.97 - 7.03 (m, 2 H), 7.04 - 7.10 (m, 2 H), 7.43 - 7.53 (m, 1 H), 7.61 (br s, 1 H), 8.10 (d, J = 1.00 Hz, 1 H), 8.18 (s, 1 H). Example 73 (53 mg), slower fraction, white solid. MS [M+H]+: 412.1.1H NMR (400 MHz, DMSO-d6 ) δ =1.35 - 1.55 (m, 2 H), 1.62 - 1.78 (m, 1 H), 1.90 - 2.03 (m, 1 H), 3.22 (dd, J = 11.07, 7.57 Hz, 1 H), 3.36 - 3.45 (m, 2 H), 3.61 (dt, J = 11.01, 4.00 Hz, 1 H), 3.72 - 3.82 (m, 3 H), 3.88 (s, 3 H), 4.07 (t, J = 4.69 Hz, 2 H), 6.90 (s, 1 H), 6.97 - 7.03 (m, 2 H), 7.04 - 7.12 (m, 2 H), 7.48 (br s, 1 H), 7.61 (br s, 1 H), 8.10 (d, J = 0.75 Hz, 1 H), 8.17 - 8.21 (m, 1 H). Example 74 6-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 6-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 74) was prepared in analogy to Example 47, by replacing iodoethane with iodomethane in step 1; Int-9a with Int-9b in step 2. MS [M+H]+: 430.1.1H NMR (400 MHz, DMSO-d6) δ = 1.41 (dtd, J = 13.27, 9.44, 9.44, 4.13 Hz, 2 H), 1.83 - 1.92 (m, 2 H), 3.53 - 3.61 (m, 1 H), 3.65 (br s, 2 H), 3.74 - 3.85 (m, 4 H), 3.88 (s, 3 H), 4.13 (dd, J = 5.32, 3.81 Hz, 2 H), 6.81 (s, 1 H), 6.84 - 6.89 (m, 1 H), 7.10 (dd, J = 12.76, 2.88 Hz, 1 H), 7.23 (t, J = 9.26 Hz, 1 H), 7.52 (br s, 1 H), 7.62 (br s, 1 H), 8.10 (d, J = 0.88 Hz, 1 H), 8.18 (s, 1 H). Example 75 6-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 6-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 75) was prepared in analogy to Example 9, by replacing Int-1b and Int- 8a with Int-1g and Int-8a in step 1. MS [M+H]+: 430.1.1H NMR (400 MHz, DMSO-d6) δ = 1.41 (dtd, J = 13.24, 9.39, 9.39, 4.13 Hz, 2 H), 1.81 - 1.98 (m, 2 H), 3.50 - 3.71 (m, 4 H), 3.72 - 3.86 (m, 4 H), 3.92 (s, 3 H), 4.16 (dd, J = 5.44, 3.94 Hz, 2 H), 6.81 - 6.89 (m, 1 H), 7.05 - 7.11 (m, 2 H), 7.21 (t, J = 9.32 Hz, 1 H), 7.42 - 7.50 (m, 1 H), 7.56 - 7.64 (m, 1 H), 8.10 - 8.13 (m, 1 H), 8.13 - 8.18 (m, 1 H). Example 76 6-[2,6-difluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 6-[2,6-difluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 76) was prepared in analogy to Example 47, by replacing iodoethane with iodomethane in step 1; Int-9a with Int-9c in step 2. MS [M+H]+: 448.0.1H NMR (400 MHz, DMSO-d6) δ = 1.42 (dtd, J = 13.23, 9.43, 9.43, 4.19 Hz, 2 H), 1.83 - 1.96 (m, 2 H), 3.33 - 3.42 (m, 2 H), 3.51 - 3.66 (m, 1 H), 3.75 - 3.86 (m, 4 H), 3.89 (s, 3 H), 4.17 (dd, J = 5.32, 3.69 Hz, 2 H) 6.83 (s, 1 H), 7.02 (d, J = 9.88 Hz, 2 H), 7.54 (br s, 1 H), 7.63 (br s, 1 H), 8.10 (d, J = 0.88 Hz, 1 H), 8.22 (s, 1 H). Example 77 1-methyl-6-[2-methyl-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxamide 1-methyl-6-[2-methyl-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5- carboxamide (Example 77) was prepared in analogy to Example 47, by replacing iodoethane with iodomethane in step 1; Int-9a with Int-9d in step 2. MS [M+H]+: 426.1.1H NMR (400 MHz, DMSO-d6) δ =1.42 (dtd, J = 13.24, 9.45, 9.45, 4.13 Hz, 2 H), 1.81 - 1.96 (m, 2 H), 2.15 (s, 3 H), 3.34 - 3.39 (m, 2 H), 3.51 - 3.63 (m, 1 H), 3.71 - 3.93 (m, 7 H), 4.09 (dd, J = 5.38, 4.00 Hz, 2 H), 6.59 (s, 1 H), 6.85 (dd, J = 8.82, 3.06 Hz, 1 H), 6.95 - 7.06 (m, 2 H), 7.51 (br s, 1 H), 7.64 (br s, 1 H), 8.08 (d, J = 0.88 Hz, 1 H), 8.17 - 8.31 (m, 1 H). Example 78 6-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 6-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 78) was prepared in analogy to Example 47, by replacing iodoethane with iodomethane in step 1; Int-9a with Int-9e in step 2. MS [M+H]+: 446.0.1H NMR (400 MHz, DMSO-d6) δ =1.41 (dtd, J = 13.21, 9.40, 9.40, 4.13 Hz, 2 H), 1.82 - 1.95 (m, 2 H), 3.34 (td, J = 10.79, 2.56 Hz, 2 H), 3.74 - 3.84 (m, 5 H), 3.87 (s, 3 H), 4.15 (dd, J = 5.38, 3.88 Hz, 2 H), 6.75 (s, 1 H), 7.01 (dd, J = 9.01, 3.00 Hz, 1 H), 7.20 (d, J = 9.01 Hz, 1 H), 7.25 (d, J = 3.00 Hz, 1 H), 7.56 (br d, J = 10.38 Hz, 2 H), 8.11 (d, J = 0.88 Hz, 1 H), 8.21 (s, 1 H). Example 79 1-methyl-6-[4-[2-(8-oxabicyclo[3.2.1]octan-3-yloxy)ethoxy]phenoxy]indazole-5- carboxamide 1-methyl-6-[4-[2-(8-oxabicyclo[3.2.1]octan-3-yloxy)ethoxy]phenoxy]indazole-5- carboxamide (Example 79) was prepared in analogy to Example 49, by replacing Int-8g with Int-8n in step 1. MS [M+H]+: 438.2.1H NMR (400 MHz, DMSO-d6) δ = 8.19 (s, 1H), 8.11 (d, J = 0.9 Hz, 1H), 7.62 (br s, 1H), 7.48 (br s, 1H), 7.09 - 7.05 (m, 2H), 7.02 - 6.98 (m, 2H), 6.90 (s, 1H), 4.34 (m, 2H), 4.08 - 4.04 (m, 2H), 3.89 (s, 3H), 3.80 - 3.71 (m, 3H), 1.97 - 1.88 (m, 2H), 1.82 - 1.73 (m, 2H), 1.73 - 1.65 (m, 2H), 1.45 - 1.35 (m, 2H). Example 80 1-methyl-6-[4-[2-(2-oxaspiro[3.3]heptan-6-yloxy)ethoxy]phenoxy]indazole-5-carboxamide 1-methyl-6-[4-[2-(2-oxaspiro[3.3]heptan-6-yloxy)ethoxy]phenoxy]indazole-5-carboxamide (Example 80) was prepared in analogy to Example 49, by replacing Int-8g with Int-8o in step 1. MS [M+H]+: 424.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.09 - 7.04 (m, 2H), 7.01 - 6.97 (m, 2H), 6.90 (s, 1H), 4.55 (s, 2H), 4.48 (s, 2H), 4.08 - 4.03 (m, 2H), 3.90 - 3.82 (m, 5H), 3.63 - 3.57 (m, 2H), 2.56 - 2.52 (m, 1H), 2.07 - 1.98 (m, 2H). Example 81 6-[4-[2-(1,1-dioxothian-4-yl)oxyethoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-[2-(1,1-dioxothian-4-yl)oxyethoxy]phenoxy]-1-methyl-indazole-5-carboxamide (Example 81) was prepared in analogy to Example 49, by replacing Int-8g with Int-8p in step 1. MS [M+H]+: 460.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.8 Hz, 1H), 7.65 - 7.59 (m, 1H), 7.51 - 7.46 (m, 1H), 7.10 - 6.99 (m, 4H), 6.91 (s, 1H), 4.17 - 4.09 (m, 2H), 3.89 (s, 3H), 3.81 - 3.75 (m, 2H), 3.75 - 3.69 (m, 1H), 3.16 - 3.00 (m, 4H), 2.15 - 2.05 (m, 4H). Example 82 1-methyl-6-[4-[2-(2-oxaspiro[3.5]nonan-7-yloxy)ethoxy]phenoxy]indazole-5-carboxamide 1-methyl-6-[4-[2-(2-oxaspiro[3.5]nonan-7-yloxy)ethoxy]phenoxy]indazole-5-carboxamide (Example 82) was prepared in analogy to Example 49, by replacing Int-8g with Int-8q in step 1. MS [M+H]+: 452.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.6 Hz, 1H), 7.60 (br s, 1H), 7.48 (br s, 1H), 7.08 - 7.03 (m, 2H), 7.01 - 6.97 (m, 2H), 6.90 (s, 1H), 4.29 - 4.21 (m, 5H), 4.08 - 4.03 (m, 2H), 3.88 (s, 3H), 3.74 - 3.69 (m, 2H), 2.00 - 1.87 (m, 2H), 1.80 - 1.67 (m, 2H), 1.57 - 1.44 (m, 2H), 1.32 - 1.20 (m, 2H). Example 83 1-methyl-6-[4-[2-(2-methyltetrahydropyran-4-yl)oxyethoxy]phenoxy]indazole-5- carboxamide 1-methyl-6-[4-[2-(2-methyltetrahydropyran-4-yl)oxyethoxy]phenoxy]indazole-5- carboxamide (Example 83) was prepared in analogy to Example 49, by replacing Int-8g with Int-8r in step 1. MS [M+H]+: 426.1.1H NMR (400 MHz, DMSO-d6) δ = 8.19 (s, 1H), 8.11 (s, 1H), 7.62 (br s, 1H), 7.48 (br s, 1H), 7.10 - 7.04 (m, 2H), 7.03 - 6.98 (m, 2H), 6.90 (s, 1H), 4.12 - 4.04 (m, 2H), 3.92 - 3.84 (m, 4H), 3.82 - 3.74 (m, 2H), 3.55 - 3.50 (m, 1H), 3.31 - 3.25 (m, 2H), 2.05 - 1.96 (m, 1H), 1.94 - 1.85 (m, 1H), 1.35 - 1.21 (m, 1H), 1.15 - 1.08 (m, 3H), 1.07 - 0.94 (m, 1H). Example 84 1-methyl-6-[4-(3-tetrahydropyran-4-ylpropoxy)phenoxy]indazole-5-carboxamide 1-methyl-6-[4-(3-tetrahydropyran-4-ylpropoxy)phenoxy]indazole-5-carboxamide (Example 84) was prepared in analogy to Example 49, by replacing Int-8g with Int-8s in step 1. MS [M+H]+: 410.3.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 1.0 Hz, 1H), 7.63 - 7.57 (m, 1H), 7.50 - 7.44 (m, 1H), 7.08 - 7.02 (m, 2H), 7.01 - 6.95 (m, 2H), 6.90 (s, 1H), 3.95 (t, J = 6.5 Hz, 2H), 3.88 (s, 3H), 3.86 - 3.80 (m, 2H), 3.29 - 3.24 (m, 2H), 1.78 - 1.69 (m, 2H), 1.63 - 1.56 (m, 2H), 1.56 - 1.46 (m, 1H), 1.40 - 1.31 (m, 2H), 1.22 - 1.09 (m, 2H). Example 85 6-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 85) was prepared in analogy to Example 47, by replacing iodoethane with iodomethane in step 1; Int-9a with Int-21b in step 2. MS [M+H]+: 429.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.67 - 7.60 (m, 1H), 7.54 - 7.49 (m, 1H), 7.28 - 7.18 (m, 1H), 7.11 - 7.04 (m, 1H), 6.87 - 6.82 (m, 2H), 4.31 - 4.23 (m, 2H), 4.08 - 4.02 (m, 2H), 3.89 (s, 3H), 3.60 - 3.56 (m, 2H), 3.50 - 3.44 (m, 2H), 2.01 - 1.93 (m, 2H). Example 86 6-[2-fluoro-4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide The titled compound was synthesized from Int-6d according to the following scheme: Step 1: 6-[2-fluoro-4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxylic acid (compound 86.1) To a solution of ethyleneurea (146.59 mg, 1.7 mmol) in DMF (5 mL) was added portionwise sodium hydride (113.52 mg, 2.84 mmol) at 0oC. The reaction was stirred for 30 minutes. Int-6d (300 mg, 0.57 mmol) was added. The reaction was slowly warmed to rt, stirred for 16 h and quenched with aq. ammonia chloride. The mixture was acidified with 6 N HCl(aq.), diluted with brine and extracted with EtOAc. The organic layer was dried in vacuum to give crude compound 86.1 (200 mg) which was used directly in the next step without further purification. MS [M+H]+: 429.1. Step 2: 6-[2-fluoro-4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 86) To a solution of compound 86.1 (200 mg, 0.47 mmol) in DMF (5 mL) were added ammonium chloride (149.83 mg, 2.8 mmol), triethylamine (472.4 mg, 4.67 mmol) and HATU (355.02 mg, 0.93 mmol). The mixture was stirred at rt for 1 h and filtered. The filtrate was concentrated in vacuum. The residue was purified by prep. HPLC to give Example 86 (30 mg). MS [M+H]+: 428.1.1H NMR (400 MHz, DMSO-d6) δ = 8.11 (s, 1H), 8.03 (d, J = 0.8 Hz, 1H), 7.58 - 7.53 (m, 1H), 7.47 - 7.41 (m, 1H), 7.20 - 7.12 (m, 1H), 7.03 - 6.96 (m, 1H), 6.80 - 6.74 (m, 2H), 6.32 - 6.11 (m, 1H), 3.98 - 3.92 (m, 2H), 3.81 (s, 3H), 3.20 - 3.09 (m, 6H), 1.88 - 1.77 (m, 2H). Example 87 6-[4-[3-(1,1-dioxo-1,2-thiazolidin-2-yl)propoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide 6-[4-[3-(1,1-dioxo-1,2-thiazolidin-2-yl)propoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide (Example 87) was prepared in analogy to Example 86, by replacing ethyleneurea with 1,2-thiazolidine 1,1-dioxide in step1. MS [M+H]+: 463.1.1H NMR (400 MHz, DMSO-d6) δ = 8.19 (s, 1H), 8.11 (s, 1H), 7.68 - 7.61 (m, 1H), 7.56 - 7.48 (m, 1H), 7.30 - 7.20 (m, 1H), 7.13 - 7.03 (m, 1H), 6.92 - 6.80 (m, 2H), 4.21 - 4.01 (m, 2H), 3.89 (s, 3H), 3.27 - 3.17 (m, 4H), 3.14 - 3.05 (m, 2H), 2.30 - 2.20 (m, 2H), 2.05 - 1.93 (m, 2H). Example 88 6-[2-fluoro-4-[3-(2-oxo-1-pyridyl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide Example 88 6-[2-fluoro-4-[3-(2-oxo-1-pyridyl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide (Example 88) was prepared in analogy to Example 86, by replacing ethyleneurea with 1H- pyridin-2-one in step1. MS [M+H]+: 437.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (s, 1H), 7.70 - 7.65 (m, 1H), 7.64 - 7.59 (m, 1H), 7.53 - 7.49 (m, 1H), 7.44 - 7.38 (m, 1H), 7.25 - 7.19 (m, 1H), 7.08 - 7.01 (m, 1H), 6.86 - 6.79 (m, 2H), 6.44 - 6.34 (m, 1H), 6.25 - 6.16 (m, 1H), 4.09 - 4.01 (m, 4H), 3.89 (s, 3H), 2.16 - 2.05 (m, 2H). Example 90 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropyl)phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-23a according to the following scheme: To a solution of Int-23a (100 mg, 0.17 mmol) in DMF (2 mL) were added ammonium chloride (45.61 mg, 0.85 mmol), triethylamine (172.57 mg, 1.71 mmol) and HATU (97.27 mg, 0.26 mmol). The mixture was stirred at rt for 1 h, diluted with water and filtered. The cake was collected and purified by prep. HPLC to give Example 90 (5 mg). MS [M+H]+: 410.1.1H NMR (400 MHz, DMSO-d6) δ = 8.19 (s, 1H), 8.13 (d, J = 0.9 Hz, 1H), 7.61 - 7.54 (m, 1H), 7.48 - 7.41 (m, 1H), 7.22 (d, J = 8.6 Hz, 2H), 7.08 (s, 1H), 7.00 - 6.94 (m, 2H), 3.92 (s, 3H), 3.85 - 3.75 (m, 2H), 3.65 - 3.57 (m, 2H), 3.45 - 3.41 (m, 2H), 3.31 - 3.29 (m, 1H), 2.66 - 2.59 (m, 2H), 1.90 - 1.70 (m, 4H), 1.45 - 1.33 (m, 2H). Example 92 1-methyl-7-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide 1-methyl-7-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide (Example 92) was prepared in analogy to Example 9, by replacing Int-8a and Int-1b with 4-(3- chloropropyl)morpholine and Int-1a in step 1. White solid, MS [M+H]+411.3.1H NMR (400 MHz, DMSO-d6) δ ppm 8.17 - 8.22 (m, 1 H), 8.15 (d, J = 3.0Hz, 1 H), 8.03 - 8.08 (m, 1 H), 7.96 (br s, 1 H), 7.27 (br s, 1 H), 7.14 - 7.17 (m, 1 H), 7.14 - 7.07 (m, 2 H), 7.04 – 7.01 (m, 2 H), 4.21 (d, J = 2.8Hz, 3 H), 4.07 – 4.02 (m, 2 H), 3.57 (d, J = 3.6Hz, 4 H), 2.32 - 2.47 (m, 6 H), 1.88 (br s, 2 H). Example 93 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl-1,2,4- triazol-3-yl)benzonitrile The titled compound was synthesized from Int-24b according to the following scheme: Step 1: 4-cyano-5-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-2-methyl- benzohydrazide (compound 93.1) To an 8 mL tube were added Int-24b (170.0 mg, 0.4 mmol), hydrazine monohydrate (100.0 mg, 1.96 mmol) and ethanol (2 mL). The mixture was stirred at 80 °C for 6 h, cooled to rt and concentrated in vacuum. The residue was purified by reversed-phase chromatography to give compound 93.1 (145.0 mg) as white solid. MS [M+H]+: 429.1. Step 2: 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl- 1,2,4-triazol-3-yl)benzonitrile (Example 93) To an 8 mL tube were added compound 93.1 (120.0 mg, 0.28 mmol), ACN (1.5 mL) and acetic acid (0.2 mL). Then MeNH2 (2M THF solution, 2.8 mL, 5.6 mmol) and DMF^DMA (43.4 mg, 0.36 mmol) were added. The mixture was stirred at 80 °C for 16 h, cooled to rt and purified directly by prep. HPLC to give Example 93 (28.71 mg) as yellow gum. MS [M+H]+: 452.1.1H NMR (400 MHz, METHANOL-d4) δ ppm 8.53 (s, 1 H), 7.81 (s, 1 H), 7.23 (t, J = 9.2Hz, 1 H), 6.92 (dd, J = 12.4, 2.8Hz, 1 H), 6.79 - 6.85 (m, 2 H), 4.34 (dd, J = 8.8, 7.2Hz, 2 H), 4.05 (t, J = 6.0Hz, 2 H), 3.66 (dd, J = 8.8, 7.6Hz, 2 H), 3.50 (s, 3 H), 3.45 (t, J = 6.8Hz, 2 H), 2.20 (s, 3 H), 2.05 (t, J = 6.4Hz, 2 H). Example 94 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl-1,2,4- triazol-3-yl)benzamide 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl-1,2,4- triazol-3-yl)benzamide (Example 94) was prepared in analogy to Example 65, by replacing Example 64 with Example 93 in step 1. MS [M+H]+: 470.2.1H NMR (400 MHz, METHANOL-d4) δ ppm 8.60 (s, 1 H), 7.95 (s, 1 H), 7.23 (t, J = 9.2Hz, 1 H), 6.90 (dd, J = 12.4, 2.8Hz, 1 H), 6.81 (dt, J = 9.2, 1.6Hz, 1 H), 6.76 (s, 1 H), 4.31 - 4.37 (m, 2 H), 4.04 (t, J = 5.6Hz, 2 H), 3.61 - 3.68 (m, 2 H), 3.51 (s, 3 H), 3.44 (t, J = 6.8Hz, 2 H), 2.21 (s, 3 H), 2.04 (quin, J = 6.4Hz, 2 H). Example 95 7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 95) was prepared in analogy to Example 9, by replacing Int-8a and Int- 1b with Int-1h and Int-8a in step 1. MS [M+H]+: 430.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.21 (s, 1 H), 8.05 (d, J = 1.0 Hz, 1 H), 7.98 (s, 1 H), 7.33 (t, J = 9.2 Hz, 1 H), 7.28 (s, 1 H), 7.14 (dd, J = 12.6 Hz, 1 H), 7.04 (s, 1 H), 6.89 (dd, J = 9.0 Hz, 1 H), 4.28 (s, 3 H), 4.11 - 4.19 (m, 2 H), 3.70 - 3.87 (m, 4 H), 3.52 - 3.62 (m, 1 H), 3.37 (d, J = 2.4Hz, 2 H), 1.78 - 1.97 (m, 2 H), 1.46 - 1.38 (m, 2 H). Example 96 1-methyl-7-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-7-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide (Example 96) was prepared in analogy to Example 31, by replacing Int-6c and 3,3- dimethylmorpholine with Int-6e and 2-oxazolidone in step 1. MS [M+H]+: 411.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (d, J = 0.8Hz, 1 H), 7.96 (br s, 1 H), 7.27 (br s, 1 H), 7.17 (d, J = 0.8Hz, 1 H), 7.08 - 7.14 (m, 2 H), 6.99 - 7.04 (m, 2 H), 4.23 - 4.28 (m, 2 H), 4.21 (s, 3 H), 4.01 (t, J = 6.4Hz, 2 H), 3.52 - 3.62 (m, 2 H), 3.33 - 3.37 (m, 2 H), 1.96 (quin, J = 6.6Hz, 2 H). Example 97 1-methyl-7-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-7-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide (Example 97) was prepared in analogy to Example 31, by replacing Int-6c and 3,3- dimethylmorpholine with Int-6e and morpholin-3-one in step 1. MS [M+H]+: 425.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.07 (s, 1 H), 7.98 (br s, 1 H), 7.28 (br s, 1 H), 7.17 (s, 1 H), 7.08 - 7.14 (m, 2 H), 6.97 - 7.05 (m, 2 H), 4.21 (s, 3 H), 3.95 - 4.05 (m, 4 H), 3.82 (t, J = 5.2Hz, 2 H), 3.48 (t, J = 6.8Hz, 2 H), 3.37 - 3.40 (m, 2 H), 1.97 (quin, J = 6.6Hz, 2 H). Example 98 1-methyl-7-[4-[3-(4-methyl-2-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-7-[4-[3-(4-methyl-2-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5- carboxamide (Example 98) was prepared in analogy to Example 31, by replacing Int-6c and 3,3-dimethylmorpholine with Int-6e and 4-methylpiperazin-2-one in step 1. MS [M+H]+: 438.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.07 (s, 1 H), 7.98 (br s, 1 H), 7.28 (br s, 1 H), 7.15 - 7.18 (m, 1 H), 7.09 - 7.14 (m, 2 H), 7.01 (br d, J = 8.8Hz, 2 H), 4.22 (s, 3 H), 3.99 (br t, J = 6.0Hz, 2 H), 3.40 - 3.53 (m, 6 H), 2.99 (br s, 2 H), 2.50 (br s, 3 H), 1.96 (quin, J = 6.4Hz, 2 H). Example 99 1-methyl-7-[4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-7-[4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5- carboxamide (Example 99) was prepared in analogy to Example 31, by replacing Int-6c and 3,3-dimethylmorpholine with Int-6e and 1-methylpiperazin-2-one in step 1. MS [M+H]+: 438.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (d, J = 0.8Hz, 1 H), 7.96 (br s, 1 H), 7.27 (br s, 1 H), 7.16 (d, J = 0.8Hz, 1 H), 7.07 - 7.13 (m, 2 H), 6.96 - 7.05 (m, 2 H), 4.21 (s, 3 H), 4.02 (t, J = 6.0Hz, 2 H), 3.28 (br s, 2 H), 2.92 - 3.15 (m, 2 H), 2.82 (s, 3 H), 2.60 - 2.77 (m, 2 H), 2.51 - 2.55 (m, 2 H), 1.92 (br s, 2 H). Example 100 1-methyl-7-[4-[3-(3-oxopiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-6e and tert-butyl 2-oxopiperazine-1- carboxylate according to the following scheme: 100.1 Example 100Step 1: tert-butyl 4-[3-[4-(5-carbamoyl-1-methyl-indazol-7-yl)oxyphenoxy]propyl]-2-oxo- piperazine-1-carboxylate (compound 100.1) To an 8 mL tube were added Int-6e (50.0 mg, 0.14 mmol), ACN (1 mL), K2CO3(58.0 mg, 0.42 mmol), tert-butyl 2-oxopiperazine-1-carboxylate (282.0 mg, 1.41 mmol) and KI (24.0 mg, 0.14 mmol). The mixture was stirred at 80 °C for 12 h, cooled to 25 °C and filtered. The filtrate was concentrated in vacuum to give compound 100.1 (50.0 mg) as light yellow oil. MS [M+K]+: 562.3. Step 2: 1-methyl-7-[4-[3-(3-oxopiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide (Example 100) To a 40 mL flask were added compound 100.1 (50.0 mg, 0.1 mmol) and 2 M HCl(g) in dioxane (5.0 mL, 10.0 mmol). The mixture was stirred at 25 °C for 2 h and concentrated in vacuum. The residue was purified by prep. HPLC to give Example 100 (27.33 mg) as yellow solid. MS [M+H]+: 424.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.06 (s, 1 H), 7.97 (br s, 2 H), 7.27 (br s, 1 H), 7.16 (s, 1 H), 7.08 - 7.14 (m, 2 H), 6.98 - 7.05 (m, 2 H), 4.21 (s, 3 H), 4.03 (br t, J = 6.0Hz, 2 H), 3.33 - 3.52 (m, 4 H), 2.63 - 2.96 (m, 4 H), 1.91 - 2.03 (m, 2 H). Example 102 7-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 7-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 102) was prepared in analogy to Example 9, by replacing Int-8a and Int-1b with Int-1i and Int-8a in step 1. Off-white solid, MS [M+H]+: 446.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.21 (s, 1H), 8.10 (d, J = 1.0Hz, 1 H), 7.99 (br s, 1H), 7.34 (d, J = 2.8 Hz, 1H), 7.29 (br s, 1H), 7.24 (d, J = 9.0 Hz, 1H), 7.21 (d, J = 0.9 Hz, 1H), 7.10 (dd, J = 9.0, 2.8Hz, 1H), 4.28 - 4.12 (m, 5 H), 3.80 -3.60 (m, 4 H), 3.64 -3.57 (m, 1H), 3.37 - 3.28 (m, 2H), 1.93 - 1.80 (m, 2H), 1.46 - 1.34 (m, 2 H). Example 103 5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole The titled compound was synthesized from Int-27f according to the following scheme: Example 103 Step 1: N-dimethylaminomethyleneamino-1-methyl-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole-5-carboxamide (compound 103.1) To an 8 mL tube were added Int-27f (100.0 mg, 0.23 mmol), DMF^DMA (40.0 mg, 0.34 mmol) and ACN (2 mL). The mixture was stirred at 60 °C for 1 h and cooled to rt. The solution of compound 103.1 (100 mg) in ACN (2 mL) was obtained and the solution was used in the next step without further purification. MS [M+H]+: 482.3. Step 2: 5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole (Example 103) To an 8 mL tube were added compound 103.1 (100.0 mg, 0.21 mmol), acetic acid (0.1 mL) and ethylamine hydrochloride (22.0 mg, 0.27 mmol). The mixture was stirred at 80 °C for 24 h, cooled to rt and concentrated in vacuum. The residue was purified by prep. HPLC to give Example 103 (37.13 mg) as yellow oil. MS [M+H]+: 464.3.1H NMR (400 MHz, DMSO-d6) δ ppm 8.60 (s, 1 H), 8.20 (s, 1 H), 7.75 (d, J = 1.2Hz, 1 H), 7.11 - 7.26 (m, 2 H), 6.95 - 7.07 (m, 2 H), 6.83 (d, J = 1.2Hz, 1 H), 4.28 (s, 3 H), 4.10 (dd, J = 5.2, 4.0Hz, 2 H), 4.05 (q, J = 7.2Hz, 2 H), 3.74 - 3.84 (m, 4 H), 3.50 - 3.61 (m, 1 H), 3.35 (d, J = 2.4Hz, 1 H), 3.30 (br d, J = 2.8Hz, 1 H), 1.80 - 1.91 (m, 2 H), 1.40 (m, 2 H), 1.24 (t, J = 7.2Hz, 3 H). Example 104 5-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide 5-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide (Example 104) was prepared in analogy to Example 9, by replacing Int-8a and Int-1b with Int-3c and Int-8a in step 1. Light yellow solid, MS [M+H]+: 416.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.71 (s, 1 H), 8.06 (br s, 1 H), 8.00 (s, 1 H), 7.76 (s, 1 H), 7.54 (t, J = 9.2Hz, 1 H), 7.43 (br s, 1 H), 7.21 (dd, J = 12.8, 2.8Hz, 1 H), 6.96 – 6.94 (m, 1 H), 6.10 (s, 1 H), 4.18 (t, J = 8.2Hz, 2 H), 3.85 - 3.77 (m, 4 H), 3.61 - 3.54 (m, 1 H), 3.39 - 3.29 (m, 2 H), 1.92 - 1.83 (m, 2 H), 1.42 (m,2 H). Example 105 7-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide 7-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 105) was prepared in analogy to Example 31, by replacing Int-6c and 3,3-dimethylmorpholine with Int-6f and oxazolidin-4-one in step 1. MS [M+Na]+: 451.2.1H NMR (400 MHz, METHANOL-d4) δ ppm 8.11 (s, 1 H), 8.01 (d, J = 1.2Hz, 1 H), 7.24 (t, J = 9.2Hz, 1 H), 7.11 (s, 1 H), 6.94 (dd, J = 12.4, 2.8Hz, 1 H), 6.84 (dt, J = 9.2, 1.2Hz, 1 H), 4.33 - 4.39 (m, 5 H), 4.08 (t, J = 6.0Hz, 2 H), 3.68 (dd, J = 8.8, 7.2Hz, 2 H), 3.61 (q, J = 7.2Hz, 2 H), 3.47 (t, J = 6.8Hz, 2 H), 2.03 - 2.12 (m, 2 H). Example 106 7-[2-fluoro-4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide 7-[2-fluoro-4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 106) was prepared in analogy to Example 31, by replacing Int-6c and 3,3-dimethylmorpholine with Int-6f and 1-methylpiperazin-2-one in step 1. MS [M+H]+:456.1.1H NMR (400 MHz, METHANOL-d4) δ ppm 8.11 (s, 1 H), 8.01 (d, J = 1.2Hz, 1 H), 7.24 (t, J = 9.2Hz, 1 H), 7.11 (s, 1 H), 6.94 (dd, J = 12.4, 2.8Hz, 1 H), 6.81 - 6.87 (m, 1 H), 4.35 (s, 3 H), 4.09 (t, J = 6.0Hz, 2 H), 3.40 (t, J = 5.6Hz, 2 H), 3.15 (s, 2 H), 2.95 (s, 3 H), 2.78 (t, J = 5.6Hz, 2 H), 2.64 (t, J = 7.2Hz, 2 H), 1.96 - 2.12 (m, 2 H). Example 108 and Example 109 7-[2-fluoro-4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide and 7-[2-fluoro-4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1- methyl-indazole-5-carboxamide The titled compound was synthesized according to the following scheme Example 108 & Example 109 Step 1: 7-[2-fluoro-4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide 7-[2-fluoro-4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Compound 108.1) was prepared in analogy to Example 30, by replacing Int-5a and 3-(2-chloroethyl)oxazolidin-2-one with Int-5c and Int-8g in step 1. MS [M+H]+: 416.2. Step 2 : 7-[2-fluoro-4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 7-[2-fluoro-4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]- 1-methyl-indazole-5-carboxamide 7-[2-fluoro-4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide and 7-[2-fluoro-4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl- indazole-5-carboxamide (Example 108 and Example 109) were prepared from Compound 108.1 in analogy to Example 4 and Example 5 by SFC. Example 108 (43 mg), faster fraction, light yellow solid. MS [M+H]+: 416.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.21 (s, 1 H), 8.05 (s, 1 H), 7.92 - 8.01 (m, 1 H), 7.33 (br t, J = 9.2Hz, 1 H), 7.25 - 7.30 (m, 1 H), 7.11 - 7.16 (m, 1 H), 7.04 (s, 1 H), 6.89 (br dd, J = 8.4, 1.2Hz, 1 H), 4.28 (s, 3 H), 4.19 - 4.24 (m, 1 H), 4.14 (br t, J = 4.4Hz, 2 H), 3.64 - 3.77 (m, 6 H), 1.90 - 2.01 (m, 2 H). Example 109 (41 mg), slower fraction, light yellow solid. MS [M+H]+: 416.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.20 (s, 1 H), 8.05 (s, 1 H), 7.98 (br d, J = 1.6Hz, 1 H), 7.33 (t, J = 9.2Hz, 1 H), 7.27 (br d, J = 2.8Hz, 1 H), 7.14 (dd, J = 12.4, 2.4Hz, 1 H), 7.04 (s, 1 H), 6.85 - 6.92 (m, 1 H), 4.28 (s, 3 H), 4.17 - 4.25 (m, 1 H), 4.14 (br t, J = 4.0Hz, 2 H), 3.71 - 3.77 (m, 3 H), 3.64 - 3.70 (m, 3 H), 1.85 - 1.99 (m, 2 H). Example 110 5-[2-fluoro-4-[3-(3-methyl-2-oxo-imidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5- a]pyridine-7-carboxamide The titled compound was synthesized from Int-6g and 1-methylimidazolidin-2-one according to the following scheme: Step 1: 5-[2-fluoro-4-[3-(3-methyl-2-oxo-imidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5- a]pyridine-7-carboxylic acid (compound 110.1) All flasks used in the reaction were heated in vacuum for 30 minutes and purged with N2 for 10 minutes. To a 50 mL flask were added 1-methylimidazolidin-2-one (264.3 mg, 2.64 mmol) and DMF (3 mL). The flask was evacuated and backfilled with N2for three times. The solution was cooled to 0 °C with an ice bath. NaH (137.3 mg, 3.43 mmol) was added in portions. The suspension was warmed to 25 °C and stirred for 1 h. KI (43.8 mg, 0.26 mmol) and a solution of Int-6g (100.0 mg, 0.26 mmol) in DMF (2 mL) were added. The resulting mixture was stirred at 50 °C for 15 h, quenched with water (10 mL) and adjusted to pH = 5-7 with formic acid. The mixture was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give compound 110.1 (21.0 mg) as light yellow solid. MS [M+H]+: 429.1. Step 2: 5-[2-fluoro-4-[3-(3-methyl-2-oxo-imidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5- a]pyridine-7-carboxamide (Example 110) To an 8 mL tube were added compound 110.1 (21.0 mg, 0.05 mmol), DMF (3 mL), NH4Cl (14.0 mg, 0.26 mmol), DIEA (0.03 mL, 0.15 mmol) and HATU (38.0 mg, 0.1 mmol). The suspension was stirred at 25 °C for 2 h and filtrated. The filtrate was concentrated in vacuum. The residue was purified by reversed-phase chromatography to give Example 110 (9.5 mg) as white solid. MS [M+H]+: 428.2.1H NMR (400 MHz, DMSO-d6) δ ppm 9.16 (br s, 1 H), 8.14 (br s, 1 H), 8.06 (s, 1 H), 8.00 (br s, 1 H), 7.54 (br t, J = 9.2Hz, 2 H), 7.18 (br dd, J = 12.8, 2.4Hz, 1 H), 6.94 (br d, J = 7.6Hz, 1 H), 6.23 (br s, 1 H), 4.06 (br t, J = 6.0Hz, 2 H), 3.21 - 3.29 (m, 6 H), 2.64 (s, 3 H), 1.85 - 1.97 (m, 2 H). Example 111 5-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide 5-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide (Example 111) was prepared in analogy to Example 110, by replacing 1- methylimidazolidin-2-one with morpholin-3-one in step 1. MS [M+H]+: 429.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.65 (s, 1 H), 8.06 (br s, 1 H), 7.99 (s, 1 H), 7.72 (s, 1 H), 7.55 (t, J = 9.2Hz, 1 H), 7.44 (br s, 1 H), 7.18 (dd, J = 3.2, 2.8Hz, 1 H), 6.93 (m, 1 H), 6.08 (s, 1 H), 4.07 (t, J = 6.0Hz, 2 H), 4.02 (s, 2 H), 3.78 - 3.86 (m, 2 H), 3.49 (t, J = 7.2Hz, 2 H), 3.37 - 3.40 (m, 2 H), 1.94 - 2.03 (m, 2 H). Example 112 5-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide 5-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide (Example 112) was prepared in analogy to Example 110, by replacing 1- methylimidazolidin-2-one with oxazolidin-2-one in step 1. MS [M+H]+: 415.2.1H NMR (400 MHz, DMSO-d6) δ ppm 9.07 (s, 1 H), 8.13 (br d, J = 4.2Hz, 1 H), 8.05 (s, 1 H), 7.95 (s, 1 H), 7.54 (t, J = 9.2Hz, 1 H), 7.50 (br s, 1 H), 7.19 (dd, J = 12.6, 2.8Hz, 1 H), 6.94 (dd, J = 9.0, 1.8Hz, 1 H), 6.21 (s, 1 H), 4.27 (t, J = 8.0 Hz, 2 H), 4.09 (t, J = 6.0Hz, 2 H), 3.55 - 3.60 (m, 2 H), 3.34 (t, J = 7.0Hz, 2 H), 1.98 (br t, J = 6.6Hz, 2 H). Example 113 5-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide 5-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide (Example 113) was prepared in analogy to Example 110, by replacing 1- methylimidazolidin-2-one with pyrrolidin-2-one in step 1. MS [M+H]+: 413.1.1H NMR (400 MHz, DMSO-d6) δ ppm 9.05 (s, 1 H), 8.12 (br s, 1 H), 8.05 (s, 1 H), 7.94 (s, 1 H), 7.54 (t, J = 9.2Hz, 1 H), 7.49 (br s, 1 H), 7.17 (dd, J = 12.6, 2.8Hz, 1 H), 6.93 (dd, J = 9.0, 1.8Hz, 1 H), 6.20 (s, 1 H), 4.04 (t, J = 6.2Hz, 2 H), 3.36 (dt, J = 10.0, 7.0Hz, 4 H), 2.17 - 2.26 (m, 2H), 1.87 - 1.98 (m, 4H). Example 114 5-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Example 114) was prepared in analogy to Example 31, by replacing 3,3-dimethylmorpholine with oxazolidin-2-one in step 1. MS [M+H]+: 397.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.59 (s, 1 H), 8.03 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.40 (br s, 1 H), 7.34 (d, J = 9.0Hz, 2 H), 7.08 (d, J = 9.2Hz, 2 H), 6.07 (s, 1 H), 4.26 (t, J = 8.0Hz, 2 H), 4.05 (t, J = 6.0Hz, 2 H), 3.53 - 3.62 (m, 2 H), 3.33 (br s, 2 H), 1.97 (quin, J = 6.6Hz, 2 H). Example 115 5-[4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide 5-[4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide (Example 115) was prepared in analogy to Example 31, by replacing 3,3-dimethylmorpholine with 2-imidazolidone in step 1. MS [M+H]+: 396.3.1H NMR (400 MHz, DMSO-d6) δ ppm 8.59 (s, 1 H), 8.02 (br s, 1 H), 7.95 (s, 1 H), 7.69 (s, 1 H), 7.38 (br s, 1 H), 7.33 (d, J = 9.2Hz, 2 H), 7.07 (d, J = 9.2Hz, 2 H), 6.28 (s, 1 H), 6.08 (s, 1 H), 4.03 (t, J = 6.4Hz, 2 H), 3.17 - 3.27 (m, 6 H), 1.88 - 1.94 (m, 2 H). Example 116 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-(4-methyl-1,2,4-triazol-3- yl)benzamide The titled compound was synthesized from Int-24a according to the following scheme: Step 1: 4-cyano-3-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]benzohydrazide (compound 116.1) To a 40 mL flask were added Int-24a (250.0 mg, 0.6 mmol), hydrazine monohydrate (215.7 mg, 4.22 mmol) and ethanol (3 mL). The mixture was stirred at 80 °C for 2 h, cooled to rt and purified by reversed-phase chromatography to give compound 116.1 (280.0 mg) as yellow oil. MS [M+H]+: 415.2. Step 2: 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-(4-methyl-1,2,4-triazol- 3-yl)benzonitrile (compound 116.2) To an 8 mL tube were added compound 116.1 (110.0 mg, 0.27 mmol), ACN (1 mL) and acetic acid (0.1 mL). Then DMF^DMA (41.0 mg, 0.35 mmol) and methylamine hydrochloride (23.3 mg, 0.35 mmol) were added. The mixture was stirred at 80 °C for 16 h, cooled to rt and purified by reversed-phase chromatography to give compound 116.2 (30.0 mg) as yellow oil. MS [M+H]+: 438.1. Step 3: 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-(4-methyl-1,2,4-triazol- 3-yl)benzamide (Example 116) To an 8 mL vial were added compound 116.2 (30.0 mg, 0.07 mmol), DMSO (1 mL), Cs2CO3 (67.0 mg, 0.21 mmol) and H2O2 (0.5 mL). The mixture was stirred at 25 °C for 0.5 h, diluted with water (0.5 mL) and ACN (0.5 mL) and filtrated. The filtrate was purified by prep. HPLC to give Example 116 (13.6 mg) as white solid. MS [M+H]+: 456.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.54 (s, 1 H), 7.85 (d, J = 8.0Hz, 1 H), 7.78 (br s, 1 H), 7.72 (br s, 1 H), 7.51 (dd, J = 8.0, 1.2Hz, 1 H), 7.32 (t, J = 9.2Hz, 1 H), 7.07 (dd, J = 12.8, 2.8Hz, 1 H), 7.04 (s, 1 H), 6.86 (dd, J = 9.2, 2.0Hz, 1 H), 4.22 - 4.29 (m, 2 H), 4.04 (t, J = 6.0Hz, 2 H), 3.68 (s, 3 H), 3.53 - 3.59 (m, 2 H), 3.30 (br s, 2 H), 1.95 (br t, J = 6.8Hz, 2 H). Example 117 4-(4-ethyl-1,2,4-triazol-3-yl)-2-[2-fluoro-4-[3-(2-oxooxazolidin-3- yl)propoxy]phenoxy]benzamide 4-(4-ethyl-1,2,4-triazol-3-yl)-2-[2-fluoro-4-[3-(2-oxooxazolidin-3- yl)propoxy]phenoxy]benzamide (Example 117) was prepared in analogy to Example 116, by replacing methylamine hydrochloride with ethylamine hydrochloride in step 2. MS [M+H]+: 470.2.1H NMR (400 MHz, DMSO-d6) δ ppm 8.64 (s, 1 H) 7.86 (d, J = 8.0Hz, 1 H) 7.79 (br s, 1 H) 7.73 (br s, 1 H) 7.45 (dd, J = 8.0, 1.2Hz, 1 H) 7.33 (t, J = 9.2Hz, 1 H) 7.08 (dd, J = 12.4, 2.8Hz, 1 H) 6.93 (s, 1 H) 6.86 (dd, J = 8.8, 1.6Hz, 1 H) 4.22 - 4.29 (m, 2 H) 3.98 - 4.07 (m, 4 H) 3.52 - 3.59 (m, 2 H) 3.30 (br s, 2 H) 1.95 (br t, J = 6.8Hz, 2 H) 1.21 (t, J = 7.2Hz, 3 H). Example 118 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-imidazol-1-yl-benzamide The titled compound was synthesized from Int-24c according to the following scheme: Example 118 Step 1: 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-imidazol-1-yl- benzonitrile (compound 118.1) A mixture of Int-24c (200.0 mg, 0.46 mmol), imidazole (47.0 mg, 0.69 mmol), copper(I) iodide (8.8 mg, 0.05 mmol), L-proline (26.4 mg, 0.23 mmol) and potassium carbonate (127.0 mg, 0.92 mmol) in DMSO (1 mL) was degassed and backfilled N2 for three times. The mixture was stirred for 12 h at 100 °C under N2,cooled to rt and diluted with water. The aqueous phase was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and filtrated. The filtrate was concentrated in vacuum. The residue was purified over column chromatography to give compound 118.1 (120.0 mg) as colorless oil. MS [M+H]+: 423.1. Step 2: 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-imidazol-1-yl- benzamide (Example 118) To a mixture of compound 118.1 (120.0 mg, 0.28 mmol) and K2CO3(90.0 mg, 0.65 mmol) in DMSO (1 mL) was added H2O2 (1 mL). The mixture was stirred at 25 °C for 2 h and filtered. The filtrate was purified by prep. HPLC to give Example 118 (17.5 mg) as white solid. MS [M+H]+: 441.1.1H NMR (400 MHz, DMSO-d6) δ ppm 8.23 (s, 1 H), 7.86 (d, J = 8.4Hz, 1 H), 7.60 - 7.72 (m, 3 H), 7.49 (dd, J = 8.4, 2.0Hz, 1 H), 7.21 (t, J = 9.2Hz, 1 H), 6.97 - 7.10 (m, 3 H), 6.74 - 6.86 (m, 1 H), 4.26 (dd, J = 8.8, 7.2Hz, 2 H), 4.03 (t, J = 6.4Hz, 2 H), 3.56 (dd, J = 8.8, 7.2Hz, 2 H), 3.31 (br s, 2 H), 1.95 (t, J = 6.8Hz, 2 H). Example 120 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-pyridazin-3-yl-benzamide The titled compound was synthesized from Int-24c according to the following scheme: Step 1: (4-cyano-3-(2-fluoro-4-(3-(2-oxooxazolidin-3-yl)propoxy)phenoxy)phenyl)boronic acid (compound 120.1) A mixture of Int-24c (300.0 mg, 0.69 mmol), bis(pinacolato)diboron (262.6 mg, 1.03 mmol), CataCxiumA Pd G2 (Sigma-Aldrich; 46.0 mg, 0.07 mmol) and potassium acetate (135.3 mg, 1.38 mmol) in 1,4-dioxane (3 mL) was degassed with N2for three times. The mixture was stirred at 80 °C for 12 h and cooled to rt. The mixture was filtered and concentrated to give crude compound 120.1 (300.0 mg) as brown oil. MS [M+H]+: 401.1. Step 2: 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-pyridazin-3-yl- benzonitrile (compound 120.2) A mixture of compound 120.1 (350.0 mg, 0.73 mmol), 3-bromopyridazine (173.0 mg, 1.09 mmol), potassium carbonate (200.6 mg, 1.45 mmol) and CataCxiumA Pd G2 (Sigma-Aldrich; 48.5 mg, 0.07 mmol) in 1,4-dioxane (3 mL) and water (1 mL) was degassed with N2for three times. The mixture was stirred at 80 °C for 12 h and cooled to rt. EtOAc (10 mL) and water (10 mL) were added and layers were separated. The aqueous phase was extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4and filtered. The filtrate was concentrated in vacuum to give compound 120.2 (200.0 mg) as brown oil. MS [M+H]+: 435.1. Step 3: 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-pyridazin-3-yl- benzamide (Example 120) To a mixture of compound 120.2 (200.0 mg, 0.46 mmol) and K2CO3 (155.6 mg, 1.13 mmol) in DMSO (1 mL) was added H2O2 (1 mL), the mixture was stirred at 25 °C for 2 h and filtered. The filtrate was purified by prep. HPLC to give Example 120 (26.0 mg) as white solid. MS [M+H]+: 453.1.1H NMR (400 MHz, DMSO-d6) δ ppm 9.20 (dd, J = 4.8, 1.6Hz, 1 H), 8.21 (dd, J = 8.8, 1.6Hz, 1 H), 7.85 - 7.94 (m, 2 H), 7.77 (dd, J = 8.8, 4.8Hz, 2 H), 7.70 (br s, 1 H), 7.58 (s, 1 H), 7.33 (t, J = 9.2Hz, 1 H), 7.09 (dd, J = 12.4, 2.8Hz, 1 H), 6.84 - 6.93 (m, 1 H), 4.26 (dd, J = 8.8, 7.2Hz, 2 H), 4.05 (t, J = 6.2Hz, 2 H), 3.57 (dd, J = 8.8, 7.2Hz, 3 H), 3.26 - 3.30 (m, 2 H), 1.90 - 2.03 (m, 2 H). Example 121 1-methyl-6-[4-[2-(tetrahydrofuran-3-ylamino)ethoxy]phenoxy]indazole-5-carboxamide 1-methyl-6-[4-[2-(tetrahydrofuran-3-ylamino)ethoxy]phenoxy]indazole-5-carboxamide (Example 121) was prepared in analogy to Example 31, by replacing Int-6c with Int-6h, 3,3- dimethylmorpholine with tetrahydrofuran-3-amine in step 1. MS [M+H]+: 397.3.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.61 (br s, 1H), 7.47 (br s, 1H), 7.09 - 7.03 (m, 2H), 7.02 - 6.97 (m, 2H), 6.90 (s, 1H), 4.00 (t, J = 5.7 Hz, 2H), 3.88 (s, 3H), 3.78 - 3.70 (m, 2H), 3.68 - 3.61 (m, 1H), 3.45 - 3.39 (m, 2H), 2.93 - 2.81 (m, 2H), 2.02 - 1.91 (m, 2H), 1.70 - 1.61 (m, 1H). Example 122 1-methyl-6-[[6-[3-(2-oxopyrrolidin-1-yl)propylamino]-3-pyridyl]oxy]indazole-5- carboxamide The titled compound was synthesized from methyl 6-bromo-1-methyl-indazole-5- carboxylateaccording to the following scheme: Step 1: methyl 6-[(6-fluoro-3-pyridyl)oxy]-1-methyl-indazole-5-carboxylate (compound 122.1) To a solution of 6-bromo-1-methyl-indazole-5-carboxylic acid methyl ester (600 mg, 2.23 mmol) in DMSO (3.6 mL) were added 6-fluoropyridin-3-ol (327.81 mg, 2.9 mmol), potassium phosphate (946.61 mg, 4.46 mmol), BPPO (Accela ChemBio; 76.79 mg, 222.97 μmol) and cuprous iodide (42.47 mg, 222.97 μmol). The reaction was stirred for 18 h at 120oC under nitrogen atmosphere. The mixture was cooled to rt, washed with brine and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuum. The residue was purified by column chromatography to give compound 122.1 (400 mg). MS [M+H]+: 302.1. Step 2: 6-[(6-fluoro-3-pyridyl)oxy]-1-methyl-indazole-5-carboxylic acid (compound 122.2) To a solution of compound 122.1 (300 mg, 995.78 μmol) in methanol (5 mL) and water (1 mL) was added lithium hydroxide monohydrate (125.35 mg, 2.99 mmol). The mixture was stirred for 3 h at 50oC, cooled to rt and acidified with acetic acid. The mixture was diluted with brine and extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuum to give compound 122.2 (230 mg). i Step 3: 6-[(6-fluoro-3-pyridyl)oxy]-1-methyl-indazole-5-carboxamide (compound 122.3) To a solution of compound 122.2 (230 mg, 800.7 μmol) in DMF (5 mL) were added ammonium chloride (256.98 mg, 4.8 mmol), triethylamine (810.22 mg, 8.01 mmol) and HATU (456.67 mg, 1.2 mmol). The mixture was stirred for 1 h at rt, diluted with brine and extracted with EtOAc. The organic layer was dried over Na2SO4and concentrated in vacuum. The residue was purified by column chromatography to give compound 122.3 (130 mg). MS [M+H]+: 287.1. Step 4: 1-methyl-6-[[6-[3-(2-oxopyrrolidin-1-yl)propylamino]-3-pyridyl]oxy]indazole-5- carboxamide (Example 122) The mixture of compound 122.3 (40 mg, 139.73 μmol), DIPEA (0.5 mL) and 1-(3- aminopropyl)pyrrolidin-2-one (100 mg) in DMF (5 mL) was stirred for 12 h at 120oC, cooled to rt and filtered. The filtrate was purified by prep. HPLC to give Example 122 (35 mg). MS [M+H]+: 409.1.1H NMR (500 MHz, DMSO-d6) δ = 8.17 (s, 1H), 8.08 (d, J = 0.8 Hz, 1H), 7.92 (d, J = 2.9 Hz, 1H), 7.65 (br s, 1H), 7.51 (br s, 1H), 7.32 - 7.28 (m, 1H), 6.82 (s, 1H), 6.59 - 6.51 (m, 2H), 3.88 (s, 3H), 3.35 - 3.33 (m, 2H), 3.28 - 3.20 (m, 4H), 2.25 - 2.18 (m, 2H), 1.96 - 1.89 (m, 2H), 1.76 - 1.70 (m, 2H). Example 123 6-[2-fluoro-4-(3-oxo-3-pyrrolidin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide 6-[2-fluoro-4-(3-oxo-3-pyrrolidin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 123) was prepared in analogy to Example 68, by replacing morpholine and Int-22a with pyrrolidine and Int-22b in step 1. MS [M+H]+: 427.1.1H NMR (500 MHz, DMSO-d6) δ = 8.17 (s, 1H), 8.10 (s, 1H), 7.63 (br s, 1H), 7.52 (br s, 1H), 7.23 (t, J = 9.2 Hz, 1H), 7.07 (dd, J = 2.8, 12.6 Hz, 1H), 6.84 (d, J = 8.9 Hz, 1H), 6.82 (s, 1H), 4.24 (t, J = 6.1 Hz, 2H), 3.88 (s, 3H), 3.52 - 3.40 (m, 2H), 3.32 - 3.29 (m, 2H), 2.74 (t, J = 6.1 Hz, 2H), 1.89 (quin, J = 6.8 Hz, 2H), 1.78 (quin, J = 6.8 Hz, 2H). Example 124 6-[2-fluoro-4-(3-morpholino-3-oxo-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide 6-[2-fluoro-4-(3-morpholino-3-oxo-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide (Example 124) was prepared in analogy to Example 68, by replacing Int-22a with Int-22b in step 1. MS [M+H]+: 443.2.1H NMR (500 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.63 (br s, 1H), 7.52 (br s, 1H), 7.23 (t, J = 9.2 Hz, 1H), 7.07 (dd, J = 2.9, 12.5 Hz, 1H), 6.86 - 6.82 (m, 2H), 4.24 (t, J = 6.1 Hz, 2H), 3.88 (s, 3H), 3.61 - 3.39 (m, 8H), 2.83 (t, J = 6.1 Hz, 2H). Example 125 6-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide 6-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 125) was prepared in analogy to Example 68, by replacing morpholine and Int-22a with 1-methylpiperazine and Int-22b in step 1. MS [M+H]+: 456.3.1H NMR (400 MHz, METHANOL-d4) δ = 8.32 (s, 1H), 7.98 (d, J = 0.9 Hz, 1H), 7.17 (t, J = 9.1 Hz, 1H), 6.87 (dd, J = 2.9, 12.3 Hz, 1H), 6.77 (ddd, J = 1.4, 2.8, 9.0 Hz, 1H), 6.63 (s, 1H), 4.23 (t, J = 6.1 Hz, 2H), 3.79 (s, 3H), 3.69 - 3.68 (m, 4H), 2.89 - 2.71 (m, 6H), 2.54 (s, 3H). Example 126 6-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]-1-methyl- indazole-5-carboxamide 6-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]-1- methyl-indazole-5-carboxamide (Example 126) was prepared in analogy to Example 68, by replacing morpholine and Int-22a with 3-oxa-6-azabicyclo[3.1.1]heptane hydrochloride and Int- 22b in step 1. MS [M+H]+: 455.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (s, 1H), 7.62 (br s, 1H), 7.51 (br s, 1H), 7.24 (t, J = 9.2 Hz, 1H), 7.07 (dd, J = 2.7, 12.6 Hz, 1H), 6.85 - 6.82 (m, 2H), 4.57 - 4.48 (m, 1H), 4.31 - 4.18 (m, 3H), 4.06 (t, J = 11.2 Hz, 2H), 3.88 (s, 3H), 3.83 (br d, J = 10.4 Hz, 1H), 3.78 - 3.70 (m, 1H), 2.76 - 2.52 (m, 3H), 1.78 (d, J = 8.3 Hz, 1H). Example 127 6-[2-fluoro-4-(3-oxo-3-piperazin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide The titled compound was synthesized from Int-22b according to the following scheme: Example 127 Step 1: tert-butyl 4-[3-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxy-3-fluoro- phenoxy]propanoyl]piperazine-1-carboxylate (compound 127.1) To a 20 mL vial were added Int-22b (160.0 mg, 0.43 mmol), DMF (3 mL), tert-butyl piperazine-1-carboxylate (120.0 mg, 0.64 mmol), HATU (245.0 mg, 0.64 mmol) and DIEA (166.0 mg, 1.29 mmol). The mixture was stirred at 20 °C for 2 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was used directly in the next step without further purification. MS [M+H]+: 542.3. Step 2: 6-[2-fluoro-4-(3-oxo-3-piperazin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5- carboxamide (Example 127) A solution of compound 127.1 (40 mg) in DCM (3 mL) in TFA (147 mg, 1.29 mmol) was stirred at rt for 16 h. The reaction was quenched with saturated NaHCO3and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 127 (20.0 mg) as white solid. MS [M+H]+: 442.1.1H NMR (400 MHz, METHANOL-d4) δ = 8.31 (s, 1H), 7.97 (d, J = 1.0 Hz, 1H), 7.16 (t, J = 9.1 Hz, 1H), 6.87 (dd, J = 2.9, 12.3 Hz, 1H), 6.76 (d, J = 9.1 Hz, 1H), 6.62 (s, 1H), 4.23 (t, J = 6.1 Hz, 2H), 3.78 (s, 3H), 3.69 (br d, J = 4.3 Hz, 4H), 3.08 - 2.97 (m, 4H), 2.85 (t, J = 6.1 Hz, 2H). Example 128 1-methyl-6-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide 1-methyl-6-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide (Example 128) was prepared in analogy to Example 68, by replacing morpholine with 3-oxa-6-azabicyclo[3.1.1]heptane hydrochloride in step 1. MS [M+H]+: 437.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (s, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.12 - 7.03 (m, J = 9.0 Hz, 2H), 7.01 - 6.95 (m, J = 9.0 Hz, 2H), 6.90 (s, 1H), 4.53 (br s, 1H), 4.28 - 4.14 (m, 3H), 4.10 - 4.04 (m, 2H), 3.88 (s, 3H), 3.83 (d, J = 10.3 Hz, 1H), 3.77 - 3.70 (m, 1H), 2.68 - 2.52 (m, 3H), 1.78 (d, J = 8.3 Hz, 1H). Example 129 1-methyl-6-[4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide 1-methyl-6-[4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide (Example 129) was prepared in analogy to Example 68, by replacing morpholine with 6-oxa-3-azabicyclo[3.1.1]heptane;4-methylbenzenesulfonic acid in step 1. MS [M+H]+: 437.1.1H NMR (500 MHz, DMSO-d6) δ = 8.19 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.62 (br s, 1H), 7.49 (br s, 1H), 7.10 - 7.04 (m, 2H), 7.02 - 6.98 (m, 2H), 6.91 (s, 1H), 4.61 (d, J = 6.4 Hz, 2H), 4.25 (t, J = 6.3 Hz, 2H), 3.89 (s, 3H), 3.81 - 3.73 (m, 2H), 3.66 (d, J = 13.6 Hz, 1H), 3.48 - 3.40 (m, 1H), 3.13 - 3.03 (m, 1H), 2.93 - 2.78 (m, 2H), 1.77 (d, J = 9.0 Hz, 1H). Example 130 6-[4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 130) was prepared in analogy to Example 68, by replacing morpholine with piperidin-4-ol hydrochloride in step 1. MS [M+H]+: 439.1.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.9 Hz, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.09 - 7.04 (m, 2H), 7.00 - 6.95 (m, 2H), 6.90 (s, 1H), 4.19 (t, J = 6.3 Hz, 2H), 4.00 - 3.84 (m, 4H), 3.71 (dtd, J = 4.1, 8.6, 12.5 Hz, 2H), 3.24 - 3.15 (m, 1H), 3.02 (ddd, J = 3.4, 9.6, 13.0 Hz, 1H), 2.89 - 2.71 (m, 2H), 1.81 - 1.63 (m, 2H), 1.41 - 1.19 (m, 2H). Example 131 6-[4-[3-(cyclopentylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-[3-(cyclopentylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide (Example 131) was prepared in analogy to Example 68, by replacing morpholine with cyclopentanamine in step 1. MS [M+H]+: 423.2.1H NMR (400 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 1.0 Hz, 1H), 7.92 (br d, J = 7.3 Hz, 1H), 7.60 (br s, 1H), 7.47 (br s, 1H), 7.09 - 7.03 (m, 2H), 6.99 - 6.94 (m, 2H), 6.90 (s, 1H), 4.16 (t, J = 6.2 Hz, 2H), 4.01 (qd, J = 6.9, 13.7 Hz, 1H), 3.88 (s, 3H), 2.54 - 2.52 (m, 2H), 1.84 - 1.74 (m, 2H), 1.69 - 1.44 (m, 4H), 1.43 - 1.33 (m, 2H). Example 132 6-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide 6-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide (Example 132) was prepared in analogy to Example 68, by replacing morpholine with N- ethylethanamine in step 1. MS [M+H]+: 411.1.1H NMR (500 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 0.8 Hz, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.09 - 7.04 (m, 2H), 7.00 - 6.96 (m, 2H), 6.90 (s, 1H), 4.20 (t, J = 6.3 Hz, 2H), 3.88 (s, 3H), 3.38 - 3.36 (m, 2H), 3.29 (q, J = 7.0 Hz, 2H), 2.77 (t, J = 6.3 Hz, 2H), 1.13 (t, J = 7.2 Hz, 3H), 1.03 (t, J = 7.0 Hz, 3H). Example 133 1-methyl-7-[4-(3-morpholino-3-oxo-propoxy)phenoxy]indazole-5-carboxamide 1-methyl-7-[4-(3-morpholino-3-oxo-propoxy)phenoxy]indazole-5-carboxamide (Example 133) was prepared in analogy to Example 68, by replacing Int-22a with Int-22c in step 1. MS [M+H]+: 425.3.1H NMR (400 MHz, DMSO-d6) δ = 8.20 (s, 1H), 8.07 (d, J = 1.4 Hz, 1H), 7.96 (br s, 1H), 7.26 (br s, 1H), 7.17 (d, J = 1.3 Hz, 1H), 7.14 - 7.07 (m, 2H), 7.04 - 6.99 (m, 2H), 4.26 - 4.16 (m, 5H), 3.61 - 3.44 (m, 8H), 2.82 (t, J = 6.3 Hz, 2H). Example 134 1-methyl-7-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide 1-methyl-7-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole- 5-carboxamide (Example 134) was prepared in analogy to Example 68, by replacing morpholine and Int-22a with 3-oxa-6-azabicyclo[3.1.1]heptane hydrochloride and Int-22c in step 1. MS [M+H]+: 437.3.1H NMR (400 MHz, DMSO-d6) δ = 8.20 (s, 1H), 8.07 (d, J = 1.3 Hz, 1H), 7.96 (br s, 1H), 7.26 (br s, 1H), 7.17 (d, J = 1.3 Hz, 1H), 7.14 - 7.08 (m, 2H), 7.05 - 6.97 (m, 2H), 4.52 (br dd, J = 4.1, 5.8 Hz, 1H), 4.28 - 4.16 (m, 6H), 4.07 (dd, J = 10.4, 13.3 Hz, 2H), 3.82 (dd, J = 1.5, 10.6 Hz, 1H), 3.73 (dd, J = 1.9, 10.3 Hz, 1H), 2.68 - 2.52 (m, 3H), 1.78 (d, J = 8.3 Hz, 1H). Example 135 7-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide 7-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide (Example 134) was prepared in analogy to Example 68, by replacing morpholine and Int-22a with N-ethylethanamine and Int-22c in step 1. MS [M+H]+: 411.3.1H NMR (400 MHz, DMSO- d6) δ = 8.20 (s, 1H), 8.07 (d, J = 1.3 Hz, 1H), 7.96 (br s, 1H), 7.26 (br s, 1H), 7.17 (d, J = 1.3 Hz, 1H), 7.13 - 7.07 (m, 2H), 7.03 - 6.98 (m, 2H), 4.24 - 4.19 (m, 5H), 3.36 - 3.26 (m, 4H), 2.78 (t, J = 6.4 Hz, 2H), 1.13 (t, J = 7.1 Hz, 3H), 1.03 (t, J = 7.1 Hz, 3H). Example 136 1-methyl-6-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide 1-methyl-6-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide (Example 136) was prepared in analogy to Example 47, by replacing iodoethane with iodomethane in step 1; Int-9a with Int-21c in step 2. MS [M+H]+: 411.2.1H NMR (500 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (d, J = 1.1 Hz, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.09 - 7.04 (m, 2H), 7.01 - 6.97 (m, 2H), 6.92 (s, 1H), 4.29 - 4.23 (m, 2H), 4.00 (t, J = 6.1 Hz, 2H), 3.89 (s, 3H), 3.59 - 3.54 (m, 2H), 3.34 - 3.32 (m, 2H), 1.95 (quin, J = 6.6 Hz, 2H). Example 137 6-[4-[2-[(3-hydroxybicyclo[1.1.1]pentane-1-carbonyl)amino]ethoxy]phenoxy]-1-methyl- indazole-5-carboxamide The titled compound was synthesized from Int-4a according to the following scheme: Step 1: tert-butyl N-[2-[4-(5-carbamoyl-1-methyl-indazol-6-yl)oxyphenoxy]ethyl]carbamate (compound 137.1) To a solution of Int-4a (284.0 mg, 1.00 mmol) and tert-butyl N-(2-bromoethyl)carbamate (896.4 mg, 4.00 mmol) in DMF (5 mL) was added K2CO3 (415.0 mg, 3.00 mmol). The mixture was stirred at 80 °C for 16 h, cooled to rt and filtered through a pad of Celite. The cake was washed with DCM. The filtrate was concentrated in vacuum. The residue was purified by column chromatography to give compound 137.1 (321.3 mg) as brown oil. MS [M+H]+: 427.1. Step 2: 6-[4-(2-aminoethoxy)phenoxy]-1-methyl-indazole-5-carboxamide (compound 137.2) To a solution of compound 137.1 (321.3 mg, 0.75 mmol) in DCM (5 mL) was added TFA (855.2 mg, 7.50 mmol). The mixture was stirred at rt for 16 h. The reaction was quenched with saturated NaHCO3 and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was used directly in the next step without further purification. MS [M+H]+: 327.1. Step 3: 6-[4-[2-[(3-hydroxybicyclo[1.1.1]pentane-1-carbonyl)amino]ethoxy]phenoxy]-1- methyl-indazole-5-carboxamide (Example 137) To a solution of crude compound 137.2 in DMF (2 mL) were added 3- hydroxybicyclo[1.1.1]pentane-1-carboxylic acid (96.0 mg, 0.75 mmol), HATU (286.0 mg, 0.75 mmol) and DIEA (324.0 mg, 2.50 mmol). The mixture was stirred at rt for 2 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified directly by prep. HPLC to give Example 137 (11.0 mg) as white solid. MS [M+H]+: 437.2.1H NMR (500 MHz, DMSO-d6) δ = 8.18 (s, 1H), 8.10 (s, 1H), 7.93 (t, J = 5.6 Hz, 1H), 7.61 (br s, 1H), 7.48 (br s, 1H), 7.08 - 7.03 (m, 2H), 7.01 - 6.97 (m, 2H), 6.91 (s, 1H), 6.29 (s, 1H), 4.01 - 3.94 (m, 2H), 3.89 (s, 3H), 3.44 - 3.37 (m, 2H), 1.95 (s, 6H). Example 138 1-methyl-2-oxo-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indoline-5-carboxamide The titled compound was synthesized from 138.1 according to the following scheme: Step 1: 6-bromo-5-(2-chloroacetyl)-1-methyl-indolin-2-one (compound 138.1) To a suspension of 6-bromo-1-methyl-indolin-2-one (2.5 g, 11.06 mmol) and aluminum chloride (5.2 g, 38.71 mmol) in 1,2-dichloroethane (40.0 mL) was added dropwise 2- chloroacetyl chloride (2.6 g, 23.22 mmol) at 0 °C. The resulting mixture was stirred at 0 °C for 20 min and then at 50 °C for 17 h. The mixture was cooled to rt and poured onto ice. The precipitate was filtered off, washed with water and dried in vacuum to give compound 138.1 (3.22 g) as brown solid. MS [M+H]+: 301.9. Step 2: 6-bromo-1-methyl-2-oxo-indoline-5-carboxylic acid (compound 138.2) A mixture of compound 138.1 (3.22 g, 10.65 mmol) and pyridine (30 mL, 371 mmol) was heated at 90 °C for 2.5 h. The formed precipitate was filtered off, washed with ethanol (25.0 mL) and dissolved in aqueous NaOH (50.0 mL, 2.5 M). The resulting mixture was heated at 80 °C for 2 h to get a dark red solution. The mixture was acidified with 5.0 M HCl(aq.)to pH = 2-3 to get yellow precipitate. The precipitate was filtered, washed with water (30.0 mL) and dried in vacuum to give compound 138.2 (2.1 g). MS [M+H]+: 269.8. Step 3: methyl 6-bromo-1-methyl-2-oxo-indoline-5-carboxylate (compound 138.3) To a suspension of compound 138.2 (2.1 g, 7.80 mmol) in MeOH (20.0 mL) was added H2SO4 (0.42 mL, 7.80 mmol) at 0 °C. The mixture was stirred at 90 °C for 16 h, cooled to rt, and concentrated in vacuum. The residue was neutralized with sat. sodium bicarbonate. The precipitate was collected, washed with water and dried in vacuum to give compound 138.3 (2.0 g). MS [M+H]+: 283.9. Step 4: methyl 6-bromo-1-methyl-2,3-dioxo-indoline-5-carboxylate (compound 138.4) To a solution of compound 138.3 (1.2 g, 4.22 mmol) in DMSO (6 mL) was added SeO2(1.2 g, 10.60 mmol). The mixture was stirred at 50 °C for 1 h, cooled to rt and quenched with water. The precipitate was collected, washed with water and dried in vacuum to give compound 138.4 (660 mg). MS [M+H]+: 297.9. Step 5: methyl 1-methyl-2,3-dioxo-6-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indoline-5-carboxylate (compound 138.5) A flask was dried by heating with a heat gun in vacuum. To this flask were added successively Int-9a (572.0 mg, 2.40 mmol), compound 138.4 (600.0 mg, 2.00 mmol), CuI (40.0 mg, 0.20 mmol), BMPPO (Accela ChemBio; 70.0 mg, 0.20 mmol), K3PO4 (850.0 mg, 4.00 mmol) and DMSO (2.5 mL). The mixture was degassed and purged with N2gas for four times and stirred at 120 °C for 16 h under N2. After cooling to rt, the mixture was diluted with ethyl acetate and filtrated through kieselguhr. The filtrate was concentrated in vacuum. The residue was purified by flash chromatography to give compound 138.5 (380.6 mg) as yellow oil. MS [M+H]+: 456.2. Step 6: 1-methyl-2,3-dioxo-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indoline-5- carboxylic acid (compound 138.6) To a 50 mL round-bottom flask were added compound 138.5 (380.6 mg, 0.84 mmol), methanol (10 mL), LiOH•H2O (106.0 mg, 2.51 mmol) and water (2 mL). The mixture was stirred at 50 °C for 16 h, cooled to rt and adjusted to pH = 5-7 with 1 M HCl(aq.). The aqueous phase was extracted with DCM. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum to give compound 138.6 (352.0 mg) which was used directly in the next step. MS [M+H]+: 442.1. Step 7: 1-methyl-2,3-dioxo-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indoline-5- carboxamide (compound 138.7) To a 20 mL vial were added compound 138.6 (370.8 mg, 0.84 mmol), DMF (8 mL), NH4Cl (225.0 mg, 4.20 mmol), HATU (480.0 mg, 1.26 mmol) and DIEA (1.09 g, 8.40 mmol). The resulting mixture was stirred at 20 °C for 2 h, diluted with water and extracted with DCM. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuum. The residue was purified directly by prep. HPLC to give compound 138.7 (265.0 mg) as white solid. MS [M+H]+: 441.1. Step 8: 1-methyl-2-oxo-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indoline-5- carboxamide (Example 138) To a 20 mL vial were added compound 138.7 (220.2 mg, 0.50 mmol), DMSO (2 mL) and N2H4•H2O (1.0 g, 20.00 mmol). The resulting mixture was stirred at 140 °C for 1 h and cooled to rt. The mixture was purified directly by prep. HPLC to give Example 138 (90.0 mg) as white solid. MS [M+H]+: 427.1.1H NMR (500 MHz, DMSO-d6) δ = 7.72 (s, 1H), 7.44 (s, 2H), 7.06 - 6.94 (m, 4H), 6.41 (s, 1H), 4.07 (dd, J = 4.0, 5.5 Hz, 2H), 3.82 - 3.73 (m, 4H), 3.58 - 3.52 (m, 3H), 3.36 - 3.31 (m, 2H), 2.99 (s, 3H), 1.89 - 1.83 (m, 2H), 1.40 (dtd, J = 4.1, 9.5, 13.3 Hz, 2H). Example 140 1-methyl-6-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-1b according to the following scheme: Example 140 Step 1: methyl 6-[4-[2-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl- indazole-5-carboxylate (compound 140.1) A solution of tert-butyl 4-(2-hydroxyethoxy)piperidine-1-carboxylate (246.73 mg, 1.01 mmol), 2-(tributylphosphoranylidene)acetonitrile (485.47 mg, 2.01 mmol) and Int-1b (300 mg, 1.01 mmol) in degassed toluene (12 mL) was sealed in a microwave tube at rt under nitrogen atmosphere. The solution was heated at 80 °C for 2 h, cooled to rt and concentrated in vacuum. The residue was purified by flash column chromatography to give the desired compound 140.1 (500 mg) as an oil. MS [M+Na]+: 548.2. Step 2: 6-[4-[2-[(1-tert-butoxycarbonyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl- indazole-5-carboxylic acid (compound 140.2) To a solution of compound 140.1 (500 mg, 951.31 μmol) in methanol (5 mL) and water (1 mL) was added lithium hydroxide monohydrate (159.67 mg, 3.81 mmol). The mixture was stirred at 50 °C for 2 h, cooled to rt and adjusted to pH = 1-2 with 4 M HCl(aq.). The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum to give the crude product compound 140.2 (0.47 g) as yellow solid. MS [M+Na]+: 534.2. Step 3: tert-butyl 4-[2-[4-(5-carbamoyl-1-methyl-indazol-6- yl)oxyphenoxy]ethoxy]piperidine-1-carboxylate (compound 140.3) A mixture of compound 140.2 (0.400 g, 781.91 μmol), ammonium chloride (209.12 mg, 3.91 mmol), triethylamine (791.21 mg, 7.82 mmol) and HATU (445.96 mg, 1.17 mmol) in DMF (4 mL) was stirred for 2 h at rt, poured into water and extracted with DCM. The combined organic layer was concentrated in vacuum. The residue was purified by flash column chromatography to give the crude product compound 140.3. MS [M+Na]+: 533.2. Step 4: 1-methyl-6-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide (Example 140) To a solution of compound 140.3 (0.100 g, 195.86 μmol) in DCM (5 mL) was added TFA (2 mL). The mixture was stirred for 1 h at rt, concentrated in vacuum and basified with sat. NaHCO3. The aqueous layer was extracted with DCM. The combined organic layer was dried over sodium sulfate and concentrated in vacuum. The residue was purified by prep. HPLC to give Example 140 (9 mg) as whitepowder. MS [M+H]+: 411.1.1H NMR (400 MHz, DMSO-d6) δ = 1.64 (dtd, 2H), 1.97 (ddd, 2H), 2.88 (ddd, 2H), 3.08 - 3.21 (m, 1H), 3.09 - 3.17 (m, 1H), 3.63 (dq, 1H), 3.75 - 3.81 (m, 2H), 3.88 (br s, 3H), 4.05 - 4.17 (m, 2H), 6.88 (s, 1H), 7.00 - 7.12 (m, 4H), 8.14 (s, 1H), 8.22 (s, 1H), 8.42 (s, 1H). Example 141 6-[4-[2-[(1-acetyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide The titled compound was synthesized from Example 140 according to the following scheme: Step 1: 6-[4-[2-[(1-acetyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 141) A solution of Example 140 (120 mg, 292.35 μmol), acetic anhydride (89.54 mg, 877.04 μmol) and DIPEA (188.92 mg, 1.46 mmol) in DCM (5 mL) was stirred at rt for 2 h and concentrated in vacuum. The residue was purified by prep. HPLC to give Example 141 (45 mg). MS [M+H]+: 453.1.1H NMR (400 MHz, DMSO-d6) δ =1.26 - 1.39 (m, 1H), 1.39 - 1.52 (m, 1H), 1.73 - 1.92 (m, 2H), 1.99 (s, 3H), 3.05 (ddd, 1H), 3.19 (ddd, 1H), 3.57 - 3.68 (m, 2H), 3.77 (dd, 2H), 3.80 - 3.86 (m, 1H), 3.88 (s, 3H), 4.09 (dd, 2H), 6.90 (s, 1H), 6.96 - 7.03 (m, 2H), 7.04 - 7.12 (m, 2H), 7.48 (br s, 1H), 7.61 (br s, 1H), 8.10 (d, 1H), 8.18 (s, 1H). Example 142 1-methyl-6-[4-(2-morpholino-2-oxo-ethoxy)phenoxy]indazole-5-carboxamide The titled compound was synthesized from Int-26 according to the following scheme: A mixture of Int-26 (200 mg, 585.96 μmol), morpholine (102.1 mg, 1.17 mmol), HATU (445.6 mg, 1.17 mmol) and Et3N (177.88 mg, 1.76 mmol) in DMF (5 mL) was stirred for 4 h at rt, poured into water and extracted with DCM. The combined organic layer was washed with water, dried over Na2SO4 and concentrated in vacuum. The residue was purified by prep. HPLC to give Example 142 as brown solid. MS [M+H]+: 411.1.1H NMR (400 MHz, DMSO-d6) δ = 3.47 (br s, 4H), 3.54 - 3.67 (m, 4H), 3.89 (s, 3H), 4.82 (s, 2H), 6.93 (s, 1H), 6.96 - 7.02 (m, 2H), 7.02 - 7.10 (m, 2H), 7.48 (br s, 1H), 7.60 (br s, 1H), 8.11 (d, 1H), 8.17 - 8.21 (m, 1H). Example 143 1-methyl-6-[4-[2-oxo-2-(tetrahydropyran-4-ylamino)ethoxy]phenoxy]indazole-5- carboxamide 1-methyl-6-[4-[2-oxo-2-(tetrahydropyran-4-ylamino)ethoxy]phenoxy]indazole-5- carboxamide (Example 143) was prepared in analogy to Example 142, by replacing morpholine with tetrahydropyran-4-amine. MS [M+H]+: NMR (400 MHz, DMSO-d6) δ =1.45 - 1.59 (m, 2H), 1.67 (br dd, 2H), 3.30 - 3.36 (m, 1H) 3.31 - 3.35 (m, 1H), 3.80 - 3.86 (m, 2H), 3.89 (s, 3H), 4.47 (s, 2H), 6.93 (s, 1H), 6.99 - 7.03 (m, 2H), 7.04 - 7.11 (m, 2H), 7.47 (br s, 1H), 7.61 (br s, 1H), 8.03 (br d, 1H), 8.11 (d, 1H), 8.18 (s, 1H). Example 144 6-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide The titled compound was synthesized from Int-21d according to the following scheme: Example 144Step 1: methyl 6-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole- 5-carboxylate (compound 144.1) To a solution of methyl 6-bromo-1-methyl-indazole-5-carboxylate (540 mg, 2.01 mmol) in DMSO (10 mL) were added Int-21d (648.43 mg, 2.41 mmol), K3PO4 (851.95 mg, 4.01 mmol), BMPPO (Accela ChemBio; 69.11 mg, 200.68 μmol) and CuI (38.22 mg, 200.68 μmol). The mixture was degassed and purged with N2gas for four times and stirred at 110 °C for 18 h under N2. The mixture was cooled, diluted with water and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4and concentrated in vacuum. The crude was purified by flash chromatography to give the crude compound 144.1 (700 mg). MS [M+H]+: 458.1. Step 2: 6-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxylic acid (compound 144.2) To a solution of compound 144.1 (300 mg, 655.81 μmol) in methanol (8 mL) and water (2 mL) was added lithium hydroxide monohydrate (82.55 mg, 1.97 mmol). The solution was heated at 50 °C for 2 h, cooled to rt and adjusted to pH = 1-2 with 4 M HCl(aq.). The mixture was extracted with DCM. The combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuum to give crude compound 144.2 (280 mg) as yellow oil. MS [M+Na]: 466.0. Step 3: 6-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide (Example 144) To a solution of compound 144.2 (280 mg, 631.46 μmol) in DMF (5 mL) were added ammonium chloride (168.88 mg, 3.16 mmol), triethylamine (319.48 mg, 3.16 mmol) and HATU (360.15 mg, 947.18 μmol). The reaction was stirred for 1 h at rt, poured into water and extracted with DCM. The combined organic layer was concentrated in vacuum. The residue was purified by prep. HPLC to give Example 144 as white solid. MS [M+H]+: 443.1.1H NMR (400 MHz, DMSO-d6) δ = 1.98 (2H), 3.31 - 3.42 (m, 1H), 3.36 - 3.42 (m, 1H), 3.48 (t, 2H), 3.80 - 3.85 (m, 2H), 3.88 (s, 3H), 3.99 - 4.10 (m, 4H), 6.80 - 6.90 (m, 2H), 7.06 (dd, 1H), 7.23 (t, 1H), 7.51 (br s, 1H), 7.62 (br s, 1H), 8.10 (d, 1H), 8.15 - 8.21 (m, 1H). Example 145 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5- a]pyridine 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5- a]pyridine was prepared in analogy to Example 103, by replacing Int-27f with Int-27a in step 1. MS [M+H]+: 450.2.1H NMR (500 MHz, DMSO-d6) δ = 8.63 (s, 2H), 7.72 - 7.66 (m, 2H), 7.42 - 7.36 (m, 2H), 7.13 - 7.06 (m, 2H), 5.98 (d, J = 1.2 Hz, 1H), 4.16 (s, 4H), 3.84 - 3.76 (m, 4H), 3.61 - 3.55 (m, 1H), 3.34-3.32 (m, 2H), 1.90 - 1.84 (m, 2H), 1.46 - 1.37 (m, 2H), 1.34 - 1.29 (m, 3H). Example 146 7-(4-methyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5 -a]pyridine 7-(4-methyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine was prepared in analogy to Example 103, by replacing Int-27f with Int-27a in step 1; ethylamine hydrochloride with methylamine hydrochloride in step 2. MS [M+H]+: 436.2.1H NMR (500 MHz, DMSO-d6) δ = 8.62 (s, 1H), 8.53 (s, 1H), 7.79 (s, 1H), 7.67 (s, 1H), 7.38 (d, J = 9.0 Hz, 2H), 7.11 (d, J = 9.0 Hz, 2H), 6.09 - 6.08 (m, 1H), 4.18 - 4.12 (m, 2H), 3.85 - 3.75 (m, 7H), 3.62 - 3.54 (m, 1H), 3.35 - 3.31 (m, 2H), 1.92 - 1.85 (m, 2H), 1.46 - 1.38 (m, 2H). Example 147 7-(4-cyclopropyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] imidazo[1,5-a]pyridine 7-(4-cyclopropyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] imidazo[1,5-a]pyridinewas prepared in analogy to Example 145, by replacing by replacing Int-27f with Int-27a in step 1; ethylamine hydrochloride with cyclopropylamine in step 2. MS [M+H]+: 462.2.1H NMR (500 MHz, DMSO-d6) δ = 8.62 (s, 1H), 8.57 (s, 1H), 8.04 (s, 1H), 7.68 (s, 1H), 7.38 (d, J = 9.2 Hz, 2H), 7.11 (d, J = 9.2 Hz, 2H), 6.24 - 6.22 (m, 1H), 4.19 - 4.13 (m, 2H), 3.86 - 3.77 (m, 4H), 3.67 - 3.62 (m, 1H), 3.61 - 3.53 (m, 1H), 3.33 - 3.30 (m, 2H), 1.91 - 1.84 (m, 2H), 1.46 - 1.38 (m, 2H), 1.12 - 1.05 (m, 2H), 1.00 - 0.94 (m, 2H). Example 148 7-[4-(2-methoxyethyl)-1,2,4-triazol-3-yl]-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] imidazo[1,5-a]pyridine 7-[4-(2-methoxyethyl)-1,2,4-triazol-3-yl]-5-[4-(2-tetrahydropyran-4-yloxyethoxy) phenoxy]imidazo[1,5-a]pyridine was prepared in analogy to Example 103, by replacing by replacing Int-27f with Int-27a in step 1; ethylamine hydrochloride with 2-methoxyethylamine in step 2. MS [M+H]+: 480.2.1H NMR (500 MHz, METHANOL-d4) δ = 8.51 (s, 1H), 8.48 (s, 1H), 7.60 (s, 1H), 7.57 (s, 1H), 7.22 - 7.18 (m, 2H), 7.01 - 6.96 (m, 2H), 5.97 (d, J = 1.2 Hz, 1H), 4.18 - 4.13 (m, 2H), 4.08 - 4.02 (m, 2H), 3.83 - 3.73 (m, 4H), 3.55 - 3.52 (m, 2H), 3.39 - 3.32 (m, 2H), 3.23 - 3.19 (m, 1H), 3.13 - 3.09 (m, 3H), 1.86 - 1.79 (m, 2H), 1.49 - 1.40 (m, 2H). Example 149 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]-1,3,4- oxadiazole 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]-1,3,4- oxadiazolewas prepared in analogy to Example 103, by replacing by replacing Int-27f with Int- 27a in step 1 and removing ethylamine hydrochloride in step 2. MS [M+H]+: 423.3.1H NMR (500 MHz, DMSO-d6) δ = 9.22 (s, 1H), 8.65 (s, 1H), 8.01 (s, 1H), 7.73 (s, 1H), 7.34 (d, J = 9.0 Hz, 2H), 7.07 (d, J = 9.2 Hz, 2H), 5.98 (d, J = 1.1 Hz, 1H), 4.13 - 4.07 (m, 2H), 3.79 - 3.70 (m, 4H), 3.55 - 3.50 (m, 1H), 3.33 - 3.30 (m, 2H), 1.85 - 1.79 (m, 2H), 1.40 - 1.34 (m, 2H). Example 150 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-7-(4H-1,2,4-triazol-3-yl)imidazo[1,5- a]pyridine The titled compound was synthesized from 7-[4-[(4-methoxyphenyl)methyl]-1,2,4-triazol- 3-yl]-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine(compound 150.1) according to the following scheme: The compound 150.1 was prepared in analogy to Example 103, by replacing Int-27f with Int-27a in step 1; ethylamine hydrochloride with 4-methoxybenzylamine in step 2. MS [M+H]+:542.2. Step 1: 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-7-(4H-1,2,4-triazol-3- yl)imidazo[1,5-a]pyridine (Example 150) A solution of compound 150.1 (200 mg, 369.28 μmol) in TFA (3 mL) was stirred for 5 h at 50oC, cooled to rt and concentrated in vacuum. The residue was diluted with sat. NaHCO3and extracted with EtOAc. The organic layer was dried over Na2SO4and concentrated in vacuum. The residue was purified by prep. HPLC to give Example 150 as white solid. MS [M+H]+: 422.1.1H NMR (500 MHz, DMSO-d6) δ = 14.07 (br s, 1H), 8.58 (s, 1H), 8.54 (s, 1H), 7.94 (s, 1H), 7.60 (s, 1H), 7.38 (d, J = 9.0 Hz, 2H), 7.12 (d, J = 9.2 Hz, 2H), 6.23 (s, 1H), 4.18 - 4.14 (m, 2H), 3.85 - 3.77 (m, 4H), 3.61 - 3.55 (m, 1H), 3.38 - 3.33 (m, 2H), 1.92 - 1.86 (m, 2H), 1.48 - 1.38 (m, 2H). Example 151 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]-1,3,4- thiadiazole The titled compound was synthesized from Int-27a according to the following scheme: Step 1: 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]- 1,3,4-thiadiazole (Example 151) A solution of Int-27a (90 mg, 218.21 μmol) in ethyl formate (1.62 g, 1.78 mL, 21.82 mmol) was stirred for 48 h at 100oC, cooled to rt and concentrated in vacuum to give compound 151.1 (90 mg) which was used in the next step without purification. MS [M+H]+: 441.2. To a solution of the above residue (90 mg, 204.34 μmol) in tetrahydrofuran (2 mL) was added Lawesson’s reagent (123.97 mg, 306.5 μmol). The reaction was stirred at 60oC for 3 h, cooled to rt and concentrated in vacuum. The residue was purified by prep. HPLC to give Example 151 as white solid. MS [M+H]+:439.1.1H NMR (400 MHz, DMSO-d6) δ = 9.57 (s, 1H), 8.68 (s, 1H), 8.08 (s, 1H), 7.73 (s, 1H), 7.42 (d, J = 9.1 Hz, 2H), 7.14 (d, J = 9.1 Hz, 2H), 6.29 (d, J = 1.4 Hz, 1H), 4.20 - 4.16 (m, 2H), 3.85 - 3.79 (m, 4H), 3.63 - 3.36 (m, 3H), 1.93 - 1.86 (m, 2H), 1.48 - 1.40 (m, 2H). Example 152 7-(4,5-dimethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo [1,5-a]pyridine The titled compound was synthesized from Int-27a according to the following scheme: Step 1: 7-(4,5-dimethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] imidazo[1,5-a]pyridine (Example 152) To a solution of N-methylacetamide (17.72 mg, 18.65 μL, 242.46 μmol) in dichloromethane (2 mL) was added 2,6-lutidine (51.96 mg, 484.92 μmol), then oxalyl chloride (30.78 mg, 242.46 μmol) was added at 0oC under nitrogen atmosphere. The reaction was stirred for 30 minutes, then a solution of Int-27a (100 mg, 242.46 μmol) in dichloromethane (0.5 mL) was added. The reaction was slowly warmed to rt, stirred for 2 h and concentrated in vacuum. The residue was used directly in the next step without further purifica...

Claims

CLAIMS 1. A compound of formula (I),wherein R1is an 8 to 10 membered bicyclic heteroaryl containing one to three heteroatoms independently selected from N, O, and S, or phenyl, wherein R1is substituted with R1a, R1b, and R1c, when R1is heteroaryl, each of R1a, R1b, and R1cis independently selected from H, halogen, C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, haloC1-6alkyl, acyl, carbamoyl, cyano, oxo, azetidinecarbonyl, and a 5 to 8 membered monocyclic heteroaryl or heterocyclyl containing one, two, three, or four heteroatoms independently selected from N, O, and S, wherein said heteroaryl and heterocyclyl can be optionally substituted by one, two, or three Q, each Q is independently selected from halogen, C1-6alkyl, deuterated C1-6alkyl, hydroxyC1-6alkyl, haloC1-6alkyl, C3-10cycloalkyl, C1-6alkoxyC1- 6alkyl, carbamoyl, and oxo, and at least one of R1a, R1b, and R1cis not H, or when R1is phenyl, each of R1a, R1b, and R1cis independently selected from H, C1-6alkyl, carbamoyl, cyano, and a 5 to 8 membered monocyclic heteroaryl containing one, two, three, or four heteroatoms independently selected from N, O, and S, wherein said heteroaryl can be optionally substituted by C1-6alkyl, and at least one of R1a, R1b, and R1cis not H; L1 is O, NH or CH2; A1 is CR3or N; A2 is CR4or N; A3 is CR5or N; A4 is CR6or N; wherein no more than two of A1to A2are N; each of R3to R6is independently selected from H, halogen and C1-6alkyl;absent; L3 is O or absent; L4 is C3-10cycloalkylene or (CH2)n, substituted with one, two, or three R7, n is 0, 1, 2, or 3, each R7is independently selected from H, halogen, and C1-6alkyl; L5 is absent or selected from O, carbonyl, NH, (CO)NH, and NH(CO); R2is selected from H, hydroxyl, C1-6alkyl, hydroxyC1-6alkyl, haloC1-6alkyl, haloC3- 10cycloalkyl, (C1-6alkyl)2amino, C1-6alkylsulfonyl, C3-10cycloalkyl, 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, 5 to 10 membered heteroaryl containing one to three heteroatoms selected from N, O, and S, and benzyl, wherein each of the heterocyclyl and heteroaryl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, halogen, C1-6alkyl, haloC1-6alkyl, C1-6alkoxyC1-6alkyl, C3-10cycloalkyC1-6alkyl, oxetan-3-ylC1-6alkyl, C3-10cycloalkyl, C1-6alkylC3-10cycloalky, C1-6alkylC1-6alkoxy, acyl, hydroxylacyl, C1-6alkoxyacyl, hydroxyl, hydroxyC1-6alkyl, C3-10cycloalkylcarbonyl, and oxo, or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1, wherein R1is an 8 to 10 membered bicyclic heteroaryl containing one to three heteroatoms independently selected from N, or phenyl, wherein R1is substituted with R1a, R1b, and R1c, when R1is heteroaryl, each of R1a, R1b, and R1cis independently selected from H, halogen, C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, haloC1-6alkyl, acyl, carbamoyl, cyano, oxo, azetidinecarbonyl, and a 5 to 8 membered monocyclic heteroaryl containing one, two, or three heteroatoms independently selected from N, O, and S, wherein said heteroaryl can be optionally substituted by one or two Q, each Q is independently selected from C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, C1-6alkoxyC1-6alkyl, and carbamoyl, and at least one of R1a, R1b, and R1cis not H, or when R1is phenyl, each of R1a, R1b, and R1cis independently selected from H, C1-6alkyl, carbamoyl, cyano, and a 5 to 8 membered monocyclic heteroaryl containing one, two, or three heteroatoms independently selected from N, O, and S, wherein said heteroaryl can be optionally substituted by C1-6alkyl, and at least one of R1a, R1b, and R1cis not H.

3. The compound according to claim 1 or claim 2, wherein R1is selected from 1H-indazolyl, imidazo[1,5-a]pyridinyl, 1H-pyrazolo[4,3-b]pyridinyl, and indolinyl, wherein R1is substituted with R1a, R1b, and R1c, R1ais on the six-member ring of R1and is selected from carbamoyl, acyl, cyano, triazolyl, oxadiazolyl, thiadiazolyl, imidazolyl, pyridazinyl, and azetidinecarbonyl, wherein R1acan be optionally substituted by one or two Q, each Q is independently selected from C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, C1-6alkoxyC1-6alkyl, and carbamoyl, R1band R1care on the five-member ring of R1and each of R1band R1cis independently selected from H, halogen, C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, haloC1-6alkyl, and oxo, or R1is phenyl substituted with R1a, R1b, and R1c, each of R1a, R1b, and R1cis independently selected from H, C1-6alkyl, carbamoyl, cyano, triazolyl, imidazolyl, and pyridazinyl, wherein the triazolyl can be optionally substituted by C1-6alkyl, and at least one of R1a, R1b, and R1cis not H.

4. The compound according to any one of claims 1 - 3, wherein R1is selected from 1H-indazolyl and imidazo[1,5-a]pyridinyl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl and triazolyl which can be optionally substituted by C1-6alkyl or C3-10cycloalkyl, R1bis on the five-member ring of R1and is selected from H, C1-6alkyl and C3-10cycloalkyl.

5. The compound according to any one of claims 1 - 4, wherein R1is selected from 1H-indazol-6-yl, 1H-indazol-7-yl, imidazo[1,5-a]pyridin-5-yl, and imidazo[1,5-a]pyridin-8-yl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl, 4-ethyl-1,2,4-triazol- 3-yl, and 4-cyclopropyl-1,2,4-triazol-3-yl, R1bis on the five-member ring of R1and is selected from H, methyl, and cyclopropyl.

6. The compound according to any one of claims 1 - 5, wherein L1 is O.

7. The compound according to any one of claims 1 - 6, wherein A1 is CR3, R3is selected from H, halogen and C1-6alkyl; A2 is CR4, R4is selected from H and halogen; A3is CR5, R5is H; and A4 is CR6, R6is selected from H and halogen.

8. The compound according to any one of claims 1 - 7, wherein A1 is CR3, R3is selected from H and halogen; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H.

9. The compound according to any one of claims 1 - 8, wherein A1 is CR3, R3is selected from H and fluoro; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H.

10. The compound according to any one of claims 1 - 9, wherein L2 is absent.

11. The compound according to any one of claims 1 - 10, wherein L4 is cyclobutylene or (CH2)n, substituted with one or two R7, n is 0, 1, 2, or 3, each R7is independently selected from H, halogen, and C1-6alkyl; 12. The compound according to any one of claims 1 - 11, wherein L4 is (CH2)n, n is 0, 2, or 3.

13. The compound according to any one of claims 1 - 12, wherein L5 is absent or selected from O and carbonyl.

14. The compound according to any one of claims 1 - 13, whereinR2is selected from H, hydroxyl, C1-6alkyl, hydroxyC1-6alkyl, (C1-6alkyl)2amino, C1-6alkylsulfonyl, C3-10cycloalkyl, 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, 5 to 10 membered heteroaryl containing one to three heteroatoms selected from N, O, and S, and benzyl, wherein each of the heterocyclyl and heteroaryl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3- 10cycloalkyC1-6alkyl, oxetan-3-ylC1-6alkyl, C3-10cycloalkyl, C1-6alkylC3-10cycloalky, acyl, hydroxylacyl, C1-6alkoxyacyl, hydroxyl, hydroxyC1-6alkyl, C3-10cycloalkylcarbonyl, and oxo.

15. The compound according to any one of claims 1 - 14, wherein R2is selected from H, hydroxyl, C1-6alkyl, hydroxyC1-6alkyl, (C1-6alkyl)2amino, C1-6alkylsulfonyl, C3-10cycloalkyl, 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, 5 to 10 membered heteroaryl containing one to three heteroatoms selected from N, O, and S, and benzyl, wherein the heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidyl, tetrahydrothiopyranyl, tetrahydropyranyl, imidazolidinyl, piperazinyl, oxazolidinyl, morpholino, isothiazolidinyl, 2-oxaspiro[3.3]heptanyl, 2-oxaspiro[3.5]nonanyl, 2-oxa-7- azaspiro[3.4]octanyl, (1R,5S)-8-azabicyclo[3.2.1]octanyl, 8-oxabicyclo[3.2.1]octanyl, 3- oxa-6-azabicyclo[3.1.1]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 2-oxa-5- azabicyclo[2.2.1]heptanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 2H-pyridinyl, 2,3- dihydrobenzofuranyl, 6,7-dihydro-4H-pyrazolo[1,5-a]pyrazinyl, 6,8-dihydro-5H- imidazo[1,5-a]pyrazinyl, 1,2-dihydroimidazolyl, and 5-azaspiro[2.4]heptanyl, and heteroaryl is selected from triazolyl and pyridyl, wherein each of the heterocyclyl and heteroaryl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3- 10cycloalkyC1-6alkyl, oxetan-3-ylC1-6alkyl, C3-10cycloalkyl, C1-6alkylC3-10cycloalky, acyl, hydroxylacyl, C1-6alkoxyacyl, hydroxyl, hydroxyC1-6alkyl, C3-10cycloalkylcarbonyl, and oxo.

16. The compound according to any one of claims 1 - 15, wherein R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S,wherein the heterocyclyl is selected from pyrrolidinyl, piperidyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperazinyl, oxazolidinyl, morpholino (1R,5S)-8-azabicyclo[3.2.1]octanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, and 6-oxa-3- azabicyclo[3.1.1]heptanyl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, acyl, C1-6alkoxyacyl, and oxo.

17. The compound according to any one of claims 1 - 16, wherein R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, wherein the heterocyclyl is selected from pyrrolidin-1-yl, 4-piperidyl, tetrahydrofuran-3- yl, tetrahydropyran-4-yl, imidazolidin-1-yl, piperazin-1-yl, oxazolidin-3-yl, morpholino, (1R,5S)-8-azabicyclo[3.2.1]octan-3-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, and 6-oxa- 3-azabicyclo[3.1.1]heptan-3-yl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, methyl, ethyl, acetyl, 2-methoxyacetyl, and oxo.

18. A compound according to claim 1 or 2, wherein R1is selected from 1H-indazolyl and imidazo[1,5-a]pyridinyl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl and triazolyl which can be optionally substituted by C1-6alkyl or C3-10cycloalkyl, R1bis on the five-member ring of R1and is selected from H, C1-6alkyl and C3- 10cycloalkyl. L1 is O; A1 is CR3, R3is selected from H and halogen; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H; L2 is absent; L3 is O or absent; L4 is (CH2)n, n is 0, 2, or 3; L5 is absent or selected from O and carbonyl;R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, wherein the heterocyclyl is selected from pyrrolidinyl, piperidyl, tetrahydrofuranyl, tetrahydropyranyl, imidazolidinyl, piperazinyl, oxazolidinyl, morpholino (1R,5S)-8-azabicyclo[3.2.1]octanyl, 3-oxa-6-azabicyclo[3.1.1]heptanyl, and 6-oxa-3- azabicyclo[3.1.1]heptanyl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, C1-6alkyl, acyl, C1-6alkoxyacyl, and oxo.

19. A compound according to claim 18, wherein R1is selected from 1H-indazol-6-yl, 1H-indazol-7-yl, imidazo[1,5-a]pyridin-5-yl, and imidazo[1,5-a]pyridin-8-yl, wherein R1is substituted with R1aand R1b, R1ais on the six-member ring of R1and is selected from carbamoyl, 4-ethyl-1,2,4-triazol- 3-yl, and 4-cyclopropyl-1,2,4-triazol-3-yl, R1bis on the five-member ring of R1and is selected from H, methyl, and cyclopropyl; L1 is O; A1 is CR3, R3is selected from H and fluoro; A2 is CR4, R4is H; A3 is CR5, R5is H; and A4 is CR6, R6is H; L2 is absent; L3 is O or absent; L4 is (CH2)n, n is 0, 2, or 3; L5 is absent or selected from O and carbonyl; R2is selected from H, hydroxyl, and 5 to 10 membered heterocyclyl containing one to three heteroatoms selected from N, O, and S, wherein the heterocyclyl is selected from pyrrolidin-1-yl, 4-piperidyl, tetrahydrofuran-3- yl, tetrahydropyran-4-yl, imidazolidin-1-yl, piperazin-1-yl, oxazolidin-3-yl, morpholino, (1R,5S)-8-azabicyclo[3.2.1]octan-3-yl, 3-oxa-6-azabicyclo[3.1.1]heptan-6-yl, and 6-oxa- 3-azabicyclo[3.1.1]heptan-3-yl, wherein the heterocyclyl is substituted with R2aand R2b, each of R2aand R2bis independently selected from H, methyl, ethyl, acetyl, 2-methoxyacetyl, and oxo.

20. A compound selected from: 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-[(1-methyl-4-piperidyl)oxy]ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 5-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 7-[4-(cyclopropylmethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-7-[4-[2-(1,2,4-triazol-4-yl)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-(2-oxopyrrolidin-1-yl)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[2-(3-methyl-2-oxo-imidazolidin-1-yl)ethoxy]phenoxy]indazole-5-carboxamide; 7-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 7-[3-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 8-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6-carboxamide; 3-methyl-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 1-methyl-8-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6- carboxamide; 5-[4-[3-(3-methylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(3-ethylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 1-methyl-7-[4-[2-(2-oxooxazolidin-3-yl)ethoxy]phenoxy]indazole-5-carboxamide;5-[4-[3-(3,3-dimethylmorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(6-oxo-2-oxa-7-azaspiro[3.4]octan-7-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 7-[4-[3-(2-benzyloxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-[3-(2-hydroxyethoxy)azetidin-1-yl]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1H-indazole-5-carboxamide; 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carbonitrile; 1-[1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5-yl]ethanone; 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 3-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-6- carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]pyrazolo[4,3-b]pyridine-5- carbonitrile; 1-methyl-6-[4-(2-tetrahydrofuran-3-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-(cyclopropoxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide; 6-[4-(3-methoxy-3-methyl-butoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide;1-methyl-6-[4-[3-(2-methyl-5-oxo-pyrrolidin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[rac-(3R,4R)-3-methyltetrahydropyran-4-yl]oxyethoxy]phenoxy]indazole-5- carboxamide; 1-methyl-6-[4-[2-[rac-(3S,4R)-3-methyltetrahydropyran-4-yl]oxyethoxy]phenoxy]indazole-5- carboxamide; 1-methyl-6-[4-(2-methyl-3-tetrahydropyran-4-yloxy-propoxy)phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(3-morpholino-3-oxo-propoxy)phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-[3-oxo-3-(3-oxopiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-(2-tetrahydropyran-3-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3S)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-[(3R)-tetrahydropyran-3-yl]oxyethoxy]phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 6-[3-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 6-[2,6-difluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[2-methyl-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 6-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[2-(8-oxabicyclo[3.2.1]octan-3-yloxy)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-(2-oxaspiro[3.3]heptan-6-yloxy)ethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-(1,1-dioxothian-4-yl)oxyethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[2-(2-oxaspiro[3.5]nonan-7-yloxy)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-(2-methyltetrahydropyran-4-yl)oxyethoxy]phenoxy]indazole-5-carboxamide;1-methyl-6-[4-(3-tetrahydropyran-4-ylpropoxy)phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[2-fluoro-4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-[3-(1,1-dioxo-1,2-thiazolidin-2-yl)propoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-[3-(2-oxo-1-pyridyl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(3-tetrahydropyran-4-yloxypropyl)phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-(3-morpholinopropoxy)phenoxy]indazole-5-carboxamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl-1,2,4-triazol-3- yl)benzonitrile; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-5-methyl-4-(4-methyl-1,2,4-triazol-3- yl)benzamide; 7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-7-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(4-methyl-2-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(3-oxopiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 7-[2-chloro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] indazole; 5-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 7-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[2-fluoro-4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide;7-[2-fluoro-4-[2-[(3S)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[2-[(3R)-tetrahydrofuran-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 5-[2-fluoro-4-[3-(3-methyl-2-oxo-imidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[2-fluoro-4-[3-(2-oxopyrrolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7- carboxamide; 5-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 5-[4-[3-(2-oxoimidazolidin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-(4-methyl-1,2,4-triazol-3- yl)benzamide; 4-(4-ethyl-1,2,4-triazol-3-yl)-2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy] benzamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-imidazol-1-yl-benzamide; 2-[2-fluoro-4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]-4-pyridazin-3-yl-benzamide; 1-methyl-6-[4-[2-(tetrahydrofuran-3-ylamino)ethoxy]phenoxy]indazole-5-carboxamide; 1-methyl-6-[[6-[3-(2-oxopyrrolidin-1-yl)propylamino]-3-pyridyl]oxy]indazole-5-carboxamide; 6-[2-fluoro-4-(3-oxo-3-pyrrolidin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 6-[2-fluoro-4-(3-morpholino-3-oxo-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 6-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]-1-methyl- indazole-5-carboxamide;6-[2-fluoro-4-(3-oxo-3-piperazin-1-yl-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole-5- carboxamide; 1-methyl-6-[4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-3-oxo-propoxy]phenoxy]indazole-5- carboxamide; 6-[4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-[3-(cyclopentylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-7-[4-(3-morpholino-3-oxo-propoxy)phenoxy]indazole-5-carboxamide; 1-methyl-7-[4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]indazole-5- carboxamide; 7-[4-[3-(diethylamino)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-[3-(2-oxooxazolidin-3-yl)propoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-[(3-hydroxybicyclo[1.1.1]pentane-1-carbonyl)amino]ethoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 1-methyl-2-oxo-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indoline-5-carboxamide; 1-methyl-6-[4-[2-(4-piperidyloxy)ethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-[(1-acetyl-4-piperidyl)oxy]ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(2-morpholino-2-oxo-ethoxy)phenoxy]indazole-5-carboxamide; 1-methyl-6-[4-[2-oxo-2-(tetrahydropyran-4-ylamino)ethoxy]phenoxy]indazole-5-carboxamide; 6-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5- a]pyridine; 7-(4-methyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5 -a]pyridine; 7-(4-cyclopropyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] imidazo[1,5-a]pyridine;7-[4-(2-methoxyethyl)-1,2,4-triazol-3-yl]-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] imidazo[1,5-a]pyridine; 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]-1,3,4- oxadiazole; 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-7-(4H-1,2,4-triazol-3-yl)imidazo[1,5- a]pyridine; 2-[5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo[1,5-a]pyridin-7-yl]-1,3,4- thiadiazole; 7-(4,5-dimethyl-1,2,4-triazol-3-yl)-5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo [1,5-a]pyridine; 3-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propan-1-ol; 3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propan-1-ol; 4-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]-2-methyl-butan-2-ol; 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(3-methylsulfonylpropoxy)phenoxy]imidazo[1,5-a]pyridine; 2-[2-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]ethoxy]ethanol; 7-(4-ethyl-1,2,4-triazol-3-yl)-5-[4-(3-methoxypropoxy)phenoxy]imidazo[1,5-a]pyridine; 5-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-7-[4-(trideuteriomethyl)-1,2,4-triazol-3- yl]imidazo[1,5-a]pyridine; 4-[3-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl]-1-methyl- piperazin-2-one; N-[3-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl] tetrahydrofuran-3-amine; 6-[3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl]-3-oxa-6- azabicyclo[3.1.1]heptane; 1-[4-[3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl]piperazin -1-yl]ethanone; 1-methyl-4-[3-[4-[7-(1,3,4-oxadiazol-2-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]propyl] piperazin-2-one;6-(4-methyl-1,2,4-triazol-3-yl)-8-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]imidazo [1,5-a]pyridine; 7-[2-fluoro-4-[3-(4-methyl-3-oxo-piperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[2-(4-piperidyloxy)ethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-[2-[(1-acetyl-4-piperidyl)oxy]ethoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-5-(4-methyl-1,2,4-triazol-3-yl)-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy] indazole; 5-(4-cyclopropyl-1,2,4-triazol-3-yl)-1-methyl-7-[4-(2-tetrahydropyran-4- yloxyethoxy)phenoxy]indazole; 7-[2-fluoro-4-(2-pyrrolidin-3-yloxyethoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 7-[4-[2-(1-acetylpyrrolidin-3-yl)oxyethoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[3-(3-oxomorpholin-4-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 7-[2-fluoro-4-[3-(2-oxa-5-azabicyclo[2.2.2]octan-5-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[4-[3-(3-ethylmorpholin-4-yl)propoxy]-2-fluoro-phenoxy]-1-methyl-indazole-5-carboxamide; 7-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 7-[2-fluoro-4-[3-[2-(hydroxymethyl)morpholin-4-yl]propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 5-imidazol-1-yl-1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole; 1-methyl-5-(3-methylimidazol-4-yl)-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole; 5-[3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenoxy]propyl]-2-oxa-5- azabicyclo[2.2.2]octane;5-[3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenoxy]propyl]-2-oxa-5- azabicyclo[2.2.1]heptane; 3-[3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenoxy]propyl]-6-oxa-3- azabicyclo[3.1.1]heptane; 6-[4-(6,8-dihydro-5H-imidazo[1,5-a]pyrazin-7-yl)phenoxy]-1-methyl-indazole-5-carboxamide; 1-methyl-6-[4-(2-methyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)phenoxy]indazole-5- carboxamide; 7-[4-[3-(2-ethylmorpholin-4-yl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 3-chloro-1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 7-[2-fluoro-4-(3-morpholino-3-oxo-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 7-[2-fluoro-4-[3-(3-oxa-6-azabicyclo[3.1.1]heptan-6-yl)-3-oxo-propoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 7-[2-fluoro-4-[3-(4-hydroxy-1-piperidyl)-3-oxo-propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 3-fluoro-1-methyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-isopropyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 1-cyclopropyl-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 6-[4-[2-[[(1S,5R)-8-azabicyclo[3.2.1]octan-3-yl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[[(1R,5S)-8-acetyl-8-azabicyclo[3.2.1]octan-3-yl]oxy]ethoxy]phenoxy]-1-methyl- indazole-5-carboxamide; 1-methyl-6-[4-[2-[[(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl]oxy]ethoxy]phenoxy] indazole-5-carboxamide; 6-[4-[2-[[(1R,5S)-8-(2-methoxyacetyl)-8-azabicyclo[3.2.1]octan-3-yl]oxy]ethoxy]phenoxy]-1- methyl-indazole-5-carboxamide; 1-methyl-6-[4-[2-[(1-methyl-4-piperidyl)oxy]ethoxy]phenoxy]indazole-5-carboxamide; 6-[4-[2-[[1-(2-methoxyacetyl)-4-piperidyl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide;6-[4-[2-[[1-(2-hydroxyacetyl)-4-piperidyl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[[1-(cyclopropanecarbonyl)-4-piperidyl]oxy]ethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-(1-acetylazetidin-3-yl)oxyethoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-[2-[1-(2-methoxyacetyl)azetidin-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[1-(2-hydroxyacetyl)azetidin-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[2-[1-(cyclopropanecarbonyl)azetidin-3-yl]oxyethoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 1-methyl-6-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 6-[4-[3-[4-(2-methoxyacetyl)piperazin-1-yl]propoxy]phenoxy]-1-methyl-indazole-5- carboxamide; 6-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1H-indazole-5-carboxamide; 1-(difluoromethyl)-6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole-5-carboxamide; 6-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-(trideuteriomethyl)indazole-5-carboxamide; 1-methyl-6-[4-(3-tetrahydropyran-4-yloxycyclobutoxy)phenoxy]indazole-5-carboxamide; 7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-5-(4-methyl-1,2,4-triazol-3- yl)indazole; 2-[7-[2-fluoro-4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]-1-methyl-indazol-5-yl]-1,3,4- oxadiazole; 7-(2,3-dihydrobenzofuran-5-yloxy)-5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazole; Azetidin-1-yl-[1-methyl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazol-5- yl]methanone; 1-methyl-7-[4-[3-(2-oxopiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; 1-methyl-5-pyridazin-3-yl-7-[4-(2-tetrahydropyran-4-yloxyethoxy)phenoxy]indazole;7-[4-(2,2-difluoro-3-morpholino-propoxy)phenoxy]-1-methyl-indazole-5-carboxamide; 1-cyclopropyl-6-[4-[3-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)-3-oxo-propoxy]phenoxy] indazole-5-carboxamide; 1-[4-[7-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenyl]-3-methyl- imidazolidin-2-one; 6-(4-ethyl-1,2,4-triazol-3-yl)-8-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]imidazo[1,5- a]pyridine; 1-[4-[3-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenoxy]propyl] piperazin-1-yl]ethanone; 4-[3-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8- yl]oxyphenoxy]propyl]morpholine; 2-[4-[7-(4-cyclopropyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-5-yl]oxyphenoxy]ethanol; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-methyl-imidazolidin-2- one; 1-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenyl]pyrrolidin-2-one; 1-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenyl]-3-methyl- imidazolidin-2-one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-methyl-imidazol-2-one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(oxetan-3- ylmethyl)imidazolidin-2-one; 1-cyclopropyl-3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7- yl]oxyphenyl]imidazolidin-2-one; 5-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-5-azaspiro[2.4]heptan-4- one; 1-ethyl-3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]imidazolidin-2- one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(2- methoxyethyl)imidazolidin-2-one;1-(cyclopropylmethyl)-3-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7- yl]oxyphenyl]imidazolidin-2-one; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(oxetan-3- ylmethyl)imidazol-2-one; 1-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8-yl]oxyphenyl]-3-(2- methoxyethyl)imidazolidin-2-one; 1-(cyclopropylmethyl)-3-[4-[6-(4-ethyl-1,2,4-triazol-3-yl)imidazo[1,5-a]pyridin-8- yl]oxyphenyl]imidazolidin-2-one; 3-[1-methyl-7-[4-(3-methyl-2-oxo-imidazol-1-yl)phenoxy]indazol-5-yl]triazole-4-carboxamide; 1-[4-[5-(4-ethyl-1,2,4-triazol-3-yl)-1-methyl-indazol-7-yl]oxyphenyl]-3-(1- methylcyclopropyl)imidazol-2-one; 7-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]-1-methyl-indazole-5-carboxamide; 5-[4-[3-(4-acetylpiperazin-1-yl)propoxy]phenoxy]imidazo[1,5-a]pyridine-7-carboxamide; 1-cyclopropyl-6-[2-fluoro-4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]indazole-5- carboxamide; 1-cyclopropyl-6-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenoxy]indazole-5-carboxamide; or a pharmaceutically acceptable salt thereof.

21. A process for the preparation of a compound having the structure of formula (Ia), (Ib), (Ic), or (Id)comprising one of the following steps: (a) Nucleophilic substitution or Mitsunobu reaction between a compound of formula VIVI and a compound of formula VII VII, provides compound of formula (Ia); (b) hydrolysis of Intermediate BIntermediate B with a base and coupling with ammonium chloride with a condensing reagent provides compound of formula (Ia), wherein the base is preferably LiOH, and the condensing reagent is preferably HATU / DIPEA; (c) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XIXI and a compound of formula VIIIA provides compound of formula (Ia); wherein the nucleophilic reagent is preferably selected from alcohol, amide, primary or secondary amine; (d) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XIIXII and a compound of formula IIA,IIA hydrolysis with a base and coupling with ammonium chloride with a condensing reagent provides compound of formula (Ia), wherein the base is preferably LiOH, and the condensing reagent is preferably HATU / DIPEA; (e) Coupling between a compound of formula Xand a compound of formula VIIAwith a condensing reagent provides Compound of formula (Ib), wherein the condensing reagent is preferably HATU / DIPEA; (f) Nucleophilic substitution or Mitsunobu reaction between a compound of formula XIVXIV and a compound of formula VII provides compound of formula (Ic); (g) Condensation of a compound of formula XVIXVI successively with (i) DMFDMA and (ii) a second reagent provides compound of formula (Ic), wherein when Z is NQ1, the second reagent is primary amine preferably selected from ethylamine and cyclopropylamine, when Z is O, the second agent is alcohol preferably methonal, when Z is S, the second reagent is Lawesson’s reagent; (h) Buchwald-Hartwig or copper catalyzed cross coupling of compound of formula XVwith a compound of formula VIIA provides compound of formula (Id); wherein ring A is selected from,bond a is connected with carbonyl and bond b is connected with oxygen, ring B is selected from:bond a is connected with the five-membered hetero-aromatic ring and bond b is connected with oxygen,X is F, Cl, Br or I; LG1is a leaving group selected from Cl, Br, I, O-tosyl, and O-mesyl; Z is O, S, or NQ1, Q1is selected from C1-6alkyl, deuterated C1-6alkyl, C3-10cycloalkyl, and C1-6alkoxyC1-6alkyl, preferably selected from methyl, trideuteriomethyl, ethyl, cyclopropyl, and methoxyethyl; R2, R3, R4, R6, L4, and L5, are as defined in any one of claims 1 to 19.

22. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20, when manufactured according to the process of claim 21.

23. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20, and a pharmaceutically acceptable excipient.

24. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 for use as therapeutically active substance.

25. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 for use in the treatment or immune mediated diseases.

26. The use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 for the treatment of immune mediated diseases.

27. The use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 for the inhibition of CDK8 and / or CDK19.

28. The use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 for the preparation of a medicament for the treatment of immune mediated diseases.

29. The use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 20 for the preparation of a medicament for the inhibition of CDK8 and / or CDK19.

30. A method for the treatment of immune mediated diseases, which method comprises administering an effective amount of a compound or a pharmaceutically acceptable salt thereof as defined in any one of claims 1 to 20.

31. The use of according to any one of claim 26 to 29, or the method according to claim 30, wherein the immune mediated diseases is Graft-versus-host disease, solid organ transplantation rejection, multiple sclerosis, rheumatoid arthritis, atopic dermatitis, psoriasis, amyotrophic lateral sclerosis or stroke.

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