Substituted thieno[3,2-b]pyridine as a protein inhibitor

Abstract

The present invention relates to General Formula I [Formula 1] JPEG2026524195000242.jpg46169 The present invention provides a compound represented by or a pharmaceutically acceptable salt thereof. These compounds are particularly useful in the treatment of cancer and neurodegenerative diseases.

Description

Detailed description of the invention

[0001] [Technical Field] This invention relates to novel heterocyclic compounds useful for therapeutic applications based on the inhibition of all kinases.

[0002] [Background technology] Protein kinases are involved in regulating numerous cellular signaling pathways (International Journal of Molecular Medicine 2017, 40, 271). Therefore, abnormal activity of various protein kinases is often associated with the development and progression of numerous diseases (particularly cancer) (Nature Reviews Cancer 2016, 16, 83). Consequently, protein kinases represent one of the most attractive targets for pharmacological inhibition, with over 70 small molecule kinase inhibitors approved for clinical use (Nature Reviews Drug Discovery 2021, 20, 839). While potent and selective inhibitors have been identified for some kinases, many others remain undiscovered (Nucleic Acids Research 2021, 49, D529).

[0003] Haploid germ cell-specific nuclear protein kinase (Haspin) (Drug Discovery Today 2018, 23, 409) phosphorylates threonine 3 of histone H3. This process begins in anaphase G2 and becomes extremely prominent in prophase and metaphase. H3T3ph plays an essential role during mitosis, providing chromatin-binding sites for the chromosome passenger complex (CPC) at the centromere and regulating chromosome segregation (Current Biology 2011, 21, 1061). Therefore, Haspin is essential for controlling cell cycle progression, namely regulating centromeric cohesion, spindle stability, and chromosome alignment. Consequently, inhibition of Haspin activity can affect the proper progression of mitosis and may even lead to abnormal chromosome segregation and mitotic catastrophe in cancer cells.

[0004] In recent years, haspin has become a new target in oncology (Oncogene 2012, 31, 1408; Cancer Research 2020, 80, 798). This is further illustrated by selected studies (summarized below).

[0005] Haspin removal has been reported to cause cell cycle abnormalities and mitotic cell death in cancer cells (FASEB Journal 2021, 35, e21923).

[0006] Haspin has been found to be overexpressed in a variety of cancers (multiple myeloma, Ewing's sarcoma, pancreatic ductal adenocarcinoma, gallbladder cancer, etc.) (Cancer Research 2020, 80, 798; Experimental Cell Research 2020, 390, 111863); therefore, modulation of Haspin activity may be particularly promising in the treatment of cancers with kinase overexpression (Scientific Reports 2019, 9, 16588; Experimental Cell Research 2019, 385, 111605). Clinically, high levels of Haspin overexpression have been confirmed to correlate with shorter patient survival (Scientific Reports 2019, 9, 16588).

[0007] In response to this, considerable effort has been made to identify haspin inhibitors. Over the past 20 years, several classes of inhibitors with different efficacy and selectivity have been reported in the literature (Journal of Pharmacy and Pharmacology 2022, https: / / doi.org / 10.1093 / jpp / rgac080).

[0008] Inhibition of haspin (by compound CHR-6494) has been found to suppress the proliferation of cancer cells (Oncogene 2012, 31, 1408; PLoS One 2021, 16, e0249912). The increasing number of reports suggests that haspin inhibition may be useful in combination with other drugs. For example, the combination of inhibiting Haspin and mTOR has been shown to induce mitotic catastrophe in KRAS-driven cancer cells (Translational Oncology 2022, 26, 101540), and more recently, synergistic inhibition of Haspin, Aurora A, or B has emerged as a promising strategy for the treatment of head and neck squamous cell carcinoma, non-small cell lung cancer, and colorectal cancer (Biochemical Pharmacology 2022, 206, 115289; Oncogene 2020, 39, 4312).

[0009] Cyclin-dependent kinase-like kinases (CDKLs) form a family of kinases whose biological properties should be further elucidated in the future (Cell Reports 2018, 22, 885).

[0010] CDKL2 has recently been recognized as a regulator of epithelial-mesenchymal transition in cancer cells (BioMed Research International 2020, article ID 1712723).

[0011] CDKL3 is a serine / threonine protein kinase whose function is not fully understood. However, inhibition or reduction of CDKL3 has been shown to induce inhibition of proliferation, migration, and cell cycle progression in human cholangiocarcinoma cells (Frontiers in Physiology 2018, 9, 234, 1-11). Furthermore, high expression of CDKL3 has been shown to promote osteosarcoma progression and to be negatively correlated with patient survival (Life Science Alliance 2020, 3, e202000648).

[0012] CDKL4 is a serine / threonine protein kinase that has been shown to influence clinical outcomes in the treatment of colorectal cancer (Oncotarget 2015, 6, 16774). Furthermore, high expression of CLK4 has been confirmed in malignant bone tumors (chordoma) (Biochimica et Biophysica Acta Reviews on Cancer 2022, 1877, 188812).

[0013] In mouse models, genetic or pharmacological inhibition of CDKL5 has been shown to reduce nephrotoxicity and ischemia-related acute kidney injury (Nature Communications 2020, 11, article number 1924).

[0014] Recent genetic studies have shown that CDKL mutations are associated with neurodevelopmental and neuropsychiatric disorders in humans (Frontiers in Behavioral Neuroscience 2010, 4, article 17).

[0015] Cdc-like kinase 2 (CLK2) is involved in numerous biological processes, including the regulation of signaling cascades and spliceosome molecular mechanisms. Its abnormal activity can lead to several diseases, including cancer (International Journal of Molecular Sciences 2020, 21, 7549; Journal of Medicinal Chemistry 2021, 64, 13191; Scientifc Reports 2021, 11, 7963). Recently, CLK2 has also been recognized as a promising therapeutic target for neurodegenerative diseases, such as Phelan-McDermid syndrome (PMDS) (including high risk for autism spectrum disorder (ASD)) and Alzheimer's disease (ChemMedChem 2018, 13, 1997; Journal of Neurochemistry 2006, 96, 1199; Science 2016, 351, 6278).

[0016] Over the past decade, several classes of CLK2 inhibitors have been reported (Journal of Medicinal Chemistry 2021, 64, 13191). The first CLK2 inhibitors have already entered clinical trials, specifically SM04690 (degenerative disc disease and osteoarthritis), SM08502 (gastrointestinal cancer and pancreatic cancer), and SM04755 (psoriasis and scleroderma) (Osteoarthritis and Cartilage 2021, 29, 654e666; Journal of Medicinal Chemistry 2021, 64, 13191).

[0017] The serine / threonine kinase PIM1 is a key protein in cellular signaling pathways (such as JAK-STAT (cellular processes) and NF-κB (cellular stimulation)) (American Journal of Cancer Research 2020, 10, 4085; Blood 2017, 130, 1418). PIM1 modulates various oncogenic pathways (such as hypoxic response, cell cycle progression, and apoptosis resistance); and is overexpressed in human cancers and associated with metastasis and overall therapeutic response. In experimental models, inhibition of PIM1 suppressed cell proliferation and migration, induced apoptotic cell death, and showed synergistic effects with other chemotherapeutic agents (Expert Opinion on Investigational Drugs 2012, 21, 425). PIM1 expression has also been found to correlate with chemotherapy resistance in prostate tumor cell lineages (Journal of Biological Chemistry 2008, 283, 20635). As a result of considerable effort to identify PIM1 inhibitors, several classes of inhibitors have been discovered (Haematologica 2010, 95, 1004; Signal Transduction and Targeted Therapy 2020, 5, 7).

[0018] Bispecific tyrosine phosphorylation-regulated kinase 2 (DYRK2) regulates proteostasis in cancer and promotes the nuclear stability and transcriptional activity of its substrate, heat shock factor 1 protein, thereby inducing protein folding (Journal of Biological Chemistry 2021, 296, 100233). Furthermore, DYRK2 is essential in regulating the Hedgehog pathway and cell growth and proliferation (eLife, 2020, 9, e57381). DYRK2 is highly expressed in prostate cancer cells, and its knockdown has been shown to significantly reduce the burden of prostate cancer in vitro and in vivo (Nature Communications 2022, 13, article number 2903). Several classes of DYRK2 inhibitors have been identified, and several DYRK2 target compounds are in the preclinical and clinical profiling stages (Journal of Biological Chemistry 2021, 296, 100233).

[0019] TAF1L kinase is primarily localized in the nucleus (within large chromatin complexes) and is essential for regulating transcriptional processes. Recently, the role of TAF1L in gastric and colorectal cancer has been identified (Pathology Oncology Research 2017, 23, 125). Overexpression of TAF1L has been shown to promote cell proliferation, migration, and invasion in esophageal squamous cell carcinoma (Journal of Cancer 2019, 10, 979; International Journal of Biological Sciences 2020, 16, 1180).

[0020] The pharmacological inhibition of TAF1L is relatively unknown, with only a few inhibitors reported in the literature; specifically, benzoisoquinoline dione inhibitors targeting the TAF1L bromodomain (Journal of Medicinal Chemistry 2017, 60, 4002.) and the triple inhibitor BAY-299 targeting BRPF2 and TAF1 / TAF1L (ChemMedChem 2019, 14, 362.).

[0021] TRB proteins play a crucial role in multiple signaling networks, and their overexpression is associated with cancer, making them novel drug targets (Biochemical Journal 2015, 467, 47). Specifically, TRB2 was identified as an oncogene that induces acute myeloid leukemia (Cancer Cell, 2006, 10, 401).

[0022] [Summary of the Invention] The present invention General formula I

[0023] [ka]

[0024] A compound represented by, The pharmaceutically acceptable salt thereof, In general formula I, R 2 It is selected from H, C1-C4 alkyl, and CF3; Y is a bond, -C(=O)-, -CH(OH)-, -C(=CH2)-, -CH2-O-, -CH2-S-, -CH2-NH2-, O, S, SO2, NR 8 , or CR 8 R 8 Selected from; R 3 teeth, C6~C14 aryl, A 3- to 10-membered heteroaryl containing at least one heteroatom selected from S, O, and N. C5-C8 cycloalkyl groups, A 5- to 8-membered heterocycloalkyl group containing at least one heteroatom selected from S, O, and N. C5-C8 cycloalkenyls, A 5- to 8-membered heterocycloalkenyl containing at least one heteroatom selected from S, O, and N. Selected from the group consisting of, Here, each substituent listed is: 3-7 membered heteroaryls containing at least one heteroatom selected from C1-C4 alkyl, C6-C10 aryl, S, O, N, 3-7 membered heterocycloalkyls containing at least one heteroatom selected from S, O, N, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, halogen, OH, HO-C1-C4 alkyl, O(C1-C4 alkyl), O(C3-C7 cycloalkyl), O(C1-C4 halogen alkyl), (C1-C4 alkyl)-O-C1-C4 alkyl, O(C5-C6 aryl) (5-6 member heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 halogen alkyl), S(C5-C6 aryl or 5-6 member heteroaryl), SO(C1-C4 alkyl), SO2(C1-C4 alkyl), CF3, C2F5, OCF3, OC2F5, amino(NH2), NH2-(C1-C4 alkyl)-, HCO-NH-(C1-C4 alkyl)-, NO2, CN, N3, C1-C4 alkylamino, di(C1-C4 alkyl)amino, (C5-C6 aryl or 5-6 member heteroaryl) Mino, di(C5~C6 aryl or heteroaryl)amino, (C1~C4 alkyl)-NH-C1~C4 alkyl, (C1~C4 alkyl)2-N-C1~C4-alkyl, =O, =S, =N-OH, -(C1~C4 alkyl)=N-OH, =NO(C1~C4 alkyl), -(C1~C4 alkyl)=NO(C1~C4 alkyl), -(C1~C4 alkyl)-CHO, -CHO, -COOH, -(C1~C4 alkyl)-COOH, -CONH2, -(C1~C4 alkyl)-CONH2, -COO(C1~C4 alkyl), -(C1~ C4 alkylene)-COO(C1~C4 alkyl), -CO(C1~C4 alkyl), -(C1~C4 alkyl)-CO(C1~C4 alkyl), -CO(C5~C6 aryl or 5~6 membered heteroaryl), -(C1~C4 alkylene)-CO(C5~C6 aryl or 5~6 membered heteroaryl), (C1~C4 alkyl)-SO2-, (C1~C4 alkyl)-SO2-(C1~C4 alkylene)-, (C1~C4 alkyl)-SO-(C1~C4 alkylene)-, (C1~C4 alkyl)-SO2-NH-,(C1~C4 alkyl)-SO2-NH-(C1~C4 alkylene)-, (C1~C4 alkyl)-SO2-N(C1~C4 alkyl)-, (C1~C4 alkyl)-SO2-N(C1~C4 alkyl)-(C1~C4 alkyl)-, (C1~C4 alkyl)-O-CO-, (C1~C4 alkyl)-O-CO-(C1~C4 alkylene)-, (C1~C4 alkyl)-NH-CO-, (C1~C4 alkyl)-NH-CO-(C1~C4 alkylene)-, (C6~C10 aryl)-NH-CO, (C6~C10 aryl)-NH-CO-(C1~C4 (C1~C4 alkyl)2N-CO-, (C1~C4 alkyl)2N-CO-(C1~C4 alkyl)-,NH2-SO2-,NH2-SO2-(C1~C4 alkyl)-, (C6~C10 aryl)-NH-SO2-, (C6~C10 aryl)-NH-SO2-(C1~C4 alkyl)-, (C1~C4 alkyl)-NH-SO2-, (C1~C4 alkyl)-NH-SO2-(C1~C4 alkyl)-, (C1~C4 alkyl)2N-SO2-, (C1~C4 alkyl)2N-SO2-(C1~C4 alkyl)-, (C1 ~C4alkyl)-CO-NH-, (C1~C4alkyl)-CO-NH-(C1~C4alkylene)-, (C1~C4alkyl)-CO-N(C1~C4alkyl)-, (C1~C4alkyl)-CO-N(C1~C4alkyl)-(C1~C4alkylene)-, (C1~C4alkyl)-OCO-NH-, (C1~C4alkyl)-OCO-NH-(C1~C4alkylene)-, (C1~C4alkyl)-OCO-N(C1~C4alkyl)-, (C1~C 4alkyl)-CO-NH-CO-, (C1~C4alkyl)-CO-N(C1~C4alkyl)-CO-, NH2-CO-NH-, (C1~C4alkyl)-NH-CO-NH-, (C1~C4alkyl)2N-CO-NH-, NH2-CO-N(C1~C4alkyl)-, (C1~C4alkyl)-NH-CO-N(C1~C4alkyl)-, (C1~C4alkyl)2N-CO-N(C1~C4alkyl)-, NH2-S(O)2-NH-, (C1~C4alkyl)-NH-S(O)2-NH-, (C1~C4alkyl)2N-S(O)2-NH-,NH2-S(O)2-N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-S(O)2-N(C1-C4 alkyl)-, (C1-C4 alkyl)2N-S(O)2-N(C1-C4 alkyl)-, (C1-C4 alkyl)2N-(C1-C4 alkylene)-CO-, (C1-C4 alkyl)2N-(C1-C4 alkylene)-SO2-, (C1-C4 alkyl)2N-(C1-C4 alkylene)-SO2-NH-, (C1-C4 alkyl)2N-(C1-C4 alkylene)-NH-SO2-, optionally substituted by at least one substituent independently selected from; X is a bond, O, S, SO2, -C(=O)-, -CH(OH)-, -CH2-O-, -CH2-S-, -CH2-NH2-, -C(=CH2)-, NR 8 or CR 8 R 8 is selected from; R 5 is C6-C14 aryl, 3- to 10-membered heteroaryl containing at least one heteroatom selected from S, O, N, C5-C8 cycloalkyl, 5- to 8-membered heterocycloalkyl containing at least one heteroatom selected from S, O, N, C5-C8 cycloalkenyl, 5- to 8-membered heterocycloalkenyl containing at least one heteroatom selected from S, O, N, is selected from the group consisting of, where each of the listed substituents is 3-7 membered heteroaryls containing at least one heteroatom selected from C1-C4 alkyl, C6-C10 aryl, S, O, N, 3-7 membered heterocycloalkyls containing at least one heteroatom selected from S, O, N, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, halogen, OH, HO-C1-C4 alkyl, O(C1-C4 alkyl), O(C3-C7 cycloalkyl), O(C1-C4 halogen alkyl), (C1-C4 alkyl)-O-C1-C4 alkyl, O(C5-C6 aryl) (5-6 member heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 halogen alkyl), S(C5-C6 aryl or 5-6 member heteroaryl), SO(C1-C4 alkyl), SO2(C1-C4 alkyl), CF3, C2F5, OCF3, OC2F5, amino(NH2), NH2-(C1-C4 alkyl)-, HCO-NH-(C1-C4 alkyl)-, NO2, CN, N3, C1-C4 alkylamino, di(C1-C4 alkyl)amino, (C5-C6 aryl or 5-6 member heteroaryl) Mino, di(C5~C6 aryl or heteroaryl)amino, (C1~C4 alkyl)-NH-C1~C4 alkyl, (C1~C4 alkyl)2-N-C1~C4-alkyl, =O, =S, =N-OH, -(C1~C4 alkyl)=N-OH, =NO(C1~C4 alkyl), -(C1~C4 alkyl)=NO(C1~C4 alkyl), -(C1~C4 alkyl)-CHO, -CHO, -COOH, -(C1~C4 alkyl)-COOH, -CONH2, -(C1~C4 alkyl)-CONH2, -COO(C1~C4 alkyl), -(C1~ C4 alkylene)-COO(C1~C4 alkyl), -CO(C1~C4 alkyl), -(C1~C4 alkyl)-CO(C1~C4 alkyl), -CO(C5~C6 aryl or 5~6 membered heteroaryl), -(C1~C4 alkylene)-CO(C5~C6 aryl or 5~6 membered heteroaryl), (C1~C4 alkyl)-SO2-, (C1~C4 alkyl)-SO2-(C1~C4 alkylene)-, (C1~C4 alkyl)-SO-(C1~C4 alkylene)-, (C1~C4 alkyl)-SO2-NH-,(C1~C4 alkyl)-SO2-NH-(C1~C4 alkylene)-, (C1~C4 alkyl)-SO2-N(C1~C4 alkyl)-, (C1~C4 alkyl)-SO2-N(C1~C4 alkyl)-(C1~C4 alkyl)-, (C1~C4 alkyl)-O-CO-, (C1~C4 alkyl)-O-CO-(C1~C4 alkylene)-, (C1~C4 alkyl)-NH-CO-, (C1~C4 alkyl)-NH-CO-(C1~C4 alkylene)-, (C6~C10 aryl)-NH-CO, (C6~C10 aryl)-NH-CO-(C1~C4 (C1~C4 alkyl)2N-CO-, (C1~C4 alkyl)2N-CO-(C1~C4 alkyl)-,NH2-SO2-,NH2-SO2-(C1~C4 alkyl)-, (C6~C10 aryl)-NH-SO2-, (C6~C10 aryl)-NH-SO2-(C1~C4 alkyl)-, (C1~C4 alkyl)-NH-SO2-, (C1~C4 alkyl)-NH-SO2-(C1~C4 alkyl)-, (C1~C4 alkyl)2N-SO2-, (C1~C4 alkyl)2N-SO2-(C1~C4 alkyl)-, (C1 ~C4alkyl)-CO-NH-, (C1~C4alkyl)-CO-NH-(C1~C4alkylene)-, (C1~C4alkyl)-CO-N(C1~C4alkyl)-, (C1~C4alkyl)-CO-N(C1~C4alkyl)-(C1~C4alkylene)-, (C1~C4alkyl)-OCO-NH-, (C1~C4alkyl)-OCO-NH-(C1~C4alkylene)-, (C1~C4alkyl)-OCO-N(C1~C4alkyl)-, (C1~C 4alkyl)-CO-NH-CO-, (C1~C4alkyl)-CO-N(C1~C4alkyl)-CO-, NH2-CO-NH-, (C1~C4alkyl)-NH-CO-NH-, (C1~C4alkyl)2N-CO-NH-, NH2-CO-N(C1~C4alkyl)-, (C1~C4alkyl)-NH-CO-N(C1~C4alkyl)-, (C1~C4alkyl)2N-CO-N(C1~C4alkyl)-, NH2-S(O)2-NH-, (C1~C4alkyl)-NH-S(O)2-NH-, (C1~C4alkyl)2N-S(O)2-NH-,NH2-S(O)2-N(C1~C4 alkyl)-, (C1~C4 alkyl)-NH-S(O)2-N(C1~C4 alkyl)-, (C1~C4 alkyl)2N-S(O)2-N(C1~C4 alkyl)-, (C1~C4 alkyl)2N-(C1~C4 alkylene)-CO-, (C1~C4 alkyl)2N-(C1~C4 alkylene)-SO2-, (C1~C4 alkyl)2N-(C1~C4 alkylene)-SO2-NH-, (C1~C4 alkyl)2N-(C1~C4 alkylene)-NH-SO2-, It may be optionally substituted by at least one substituent independently selected from; R6 is selected from H, C1-C4 alkyl, and CF3; R7 is H, C1-C4 alkyl, F, Cl, Br, OR 8 , and selected from CF3; R 8 These are independently selected from H and C1-C4 alkyl groups. Compounds or their pharmaceutically acceptable salts, Regarding.

[0025] The compound represented by formula I may be in the form of a free base or an addition salt with a pharmaceutically acceptable organic or inorganic acid such as hydrochloric acid. Other suitable pharmaceutically acceptable acids include acetic acid, aspartic acid, benzenesulfonic acid, benzoic acid, besylic acid, bicarbonate, tartaric acid, hydrobromic acid, camsylic acid, carbonic acid, citric acid, decanoic acid, edetic acid, esylic acid, fumaric acid, gluceptic acid, gluconic acid, glutamic acid, glycolic acid, hexanoic acid, hydroxynaphthic acid, hydroiodic acid, isethionic acid, lactic acid, lactobionic acid, malic acid, maleic acid, mandelic acid, methanesulfonic acid, methylsulfonic acid, mucoic acid, napsylic acid, nitric acid, octanoic acid, oleic acid, pamoic acid, pantothenic acid, phosphonic acid, polygalacturonic acid, propionic acid, salicylic acid, stearic acid, succinic acid, sulfonic acid, tartaric acid, teoclic acid, and toluenesulfonic acid.

[0026] The halogen is selected from fluorine, chlorine, bromine, and iodine.

[0027] Alkyls are branched or straight-chain saturated hydrocarbons.

[0028] Alkenyls are branched or straight-chain hydrocarbons that contain at least one double bond.

[0029] Alkylenes are divalent, branched or linear, preferably linear, hydrocarbons. A preferred alkylene is methylene.

[0030] Cycloalkyls are saturated hydrocarbons that contain at least one aliphatic ring.

[0031] Cycloalkenyls are hydrocarbons that contain at least one aliphatic ring and at least one double bond within that ring.

[0032] Aryls are hydrocarbons that contain at least one aromatic ring. Examples of aryls include phenyl and benzyl.

[0033] A heteroaryl is a heterohydrocarbon containing at least one aromatic ring that includes at least one heteroatom selected from O, S, and N.

[0034] A heterocyclyl or cycloheteralkyl is a heterohydrocarbon containing at least one aliphatic ring, the ring containing at least one heteroatom selected from O, S, and N.

[0035] A cycloheteralkenyl is a heterohydrocarbon containing at least one double bond and at least one aliphatic ring, the ring containing at least one heteroatom selected from O, S, and N.

[0036] Therefore, a cyclic structure may contain one or more rings, which may be conjugated or connected by C1-C3 linkers.

[0037] Preferably, R 2The element is selected from H, methyl, and ethyl.

[0038] Preferably, Y is selected from the bonds, -C(=O)-, -CH(OH)-, -C(=CH2)-, -NH-, and -N(CH3)-.

[0039] Preferably, R 3 teeth, C6-C10 aryls, and A 5-10 member heteroaryl containing at least one heteroatom selected from S, O, and N. Selected from the group consisting of, Here, the aryl or heteroaryl can be optionally substituted.

[0040] Preferably, R 3 teeth, Phenyl, and, A 5-10 member heteroaryl comprising at least one heteroatom N and optionally at least one other heteroatom selected from S, O, and N. Selected from the group consisting of, Here, the phenyl or heteroaryl can be optionally substituted.

[0041] Preferably, R 3 teeth, Selected from the group consisting of pyridinyl, phenyl, thiazolyl, thiadiazolyl, isothiazolyl, pyrimidinyl, pyridadinyl, pyrazolyl, pyrrolopyridinyl, quinazolinyl, quinoxalinyl, indazolyl, triazolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, imidazopyridinyl, dihydropyridinyl, and tetrahydropyridinyl, Here, any of these substituents can be arbitrarily substituted.

[0042] Preferably, R 3 teeth, It is substituted with one or more substituents independently selected from C1-C4 alkyl (preferably methyl), halogen (preferably fluorine), morpholinyl, benzyl, amino, aminomethyl, and trifluoromethyl.

[0043] Preferably, X is selected from a bond, -NH-, -N(CH3)-, -O-, -S-, -CH2-O-, -CH2-NH2-, and -C(=CH2)-.

[0044] R 5 Preferably, Selected from the group consisting of 5-10 membered heteroaryls containing at least one heteroatom selected from C6-C10 aryls, S, O, and N, and 5-6 membered heterocycloalkyls containing at least one heteroatom selected from S, O, and N, Here, the aryl, heteroaryl, or heterocycloalkyl group can be optionally substituted.

[0045] R 5 Preferably, Phenyl, Morpholinil, and, A 5-10 member heteroaryl comprising at least one heteroatom N and optionally at least one other heteroatom selected from S, O, and N. Selected from the group consisting of, Here, the phenyl, morpholinyl, and heteroaryl can be optionally substituted.

[0046] R 5 Preferably, Selected from the group consisting of pyrazolyl, phenyl, morpholinyl, imidazolyl, isothiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyridadinyl, pyrazolopyrimidinyl, furanil, and isoxazolyl, Here, any of these substituents can be arbitrarily substituted.

[0047] R 5 Preferably, Substituting with one or more substituents independently selected from C1-C4 alkyl (preferably methyl, ethyl, isopropyl, tert-butyl), trifluoromethyl, benzyl, phenyl, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, amino, halogen (preferably F), -COO(C1-C4 alkyl), C1-C4 alkylthio, C1-C4 alkoxy, and CN.

[0048] Preferably, R 6 The element is selected from H, C1-C4 alkyl (preferably methyl), and phenyl.

[0049] Preferably, R 7 The element is selected from H, C1-C4 alkyl (preferably methyl), F, Cl, Br, and O(C1-C4 alkyl) (preferably methoxy).

[0050] Particularly preferred are the following compounds (in the form of a free base or a salt with a pharmaceutically acceptable acid):

[0051] [ka]

[0052] In another embodiment, the present invention provides a compound represented by formula I for use as a pharmaceutical.

[0053] Compounds represented by formula I are suitable for the treatment of diseases involving CDKL, CLK, DYRK, Haspin, PIM, TAF1L, and / or TRB kinases.

[0054] In particular, compounds represented by formula I are suitable for use in the treatment of cancer or neurodegenerative diseases.

[0055] More specifically, compounds represented by formula I are suitable for use in the treatment of leukemia (such as acute myeloid leukemia); autoimmune diseases (such as rheumatoid arthritis or autoimmune hepatitis); peripheral neuropathic pain; cancer (such as non-small cell lung cancer (NSCLC), ovarian cancer, glioblastoma, breast cancer, lung cancer, lung adenocarcinoma, pancreatic cancer, prostate cancer, brain tumor, ovarian cancer, colorectal cancer, liver cancer, hepatocellular carcinoma, squamous cell carcinoma); periodontitis; pulmonary fibrosis; obesity; insulin resistance; obesity-induced hyperinsulinemia; arteriosclerosis; and neurodegenerative disorders (such as Alzheimer's disease).

[0056] Compounds represented by formula I may be formulated using methods known to those skilled in the field of pharmaceutical formulation. A pharmaceutical composition contains at least one compound represented by formula I or a pharmaceutically acceptable salt thereof, and at least one auxiliary compound. The auxiliary compound may be selected from fillers, binders, solvents, lubricants, and preservatives in particular.

[0057] [Examples] I. Preparation example [material and method] All commercially available reagents were used as supplied without further purification. Reaction solvents were purchased anhydrous and stored under a nitrogen atmosphere. Unless otherwise specified, reactions were carried out under a nitrogen atmosphere using oven-dried glassware. Column chromatography was performed using silica gel (pore size 60 Å, particle size 230–400 mesh, particle size 40–63 μm). Purification by thin-layer chromatography for preparation was performed using Merck plates (PLC Silica gel 60 F). 254 The procedure was performed using a 1 mm reversed-phase column chromatography. 18The analysis was performed using reversed-phase silica gel (pore size 90 Å, particle size 230-400 mesh, particle size 40-63 μm). NMR spectra were acquired in the specified deuterated solvent; chemical shifts were expressed in parts per million (δ) relative to the appropriate deuterated solvent used. Multiplicity was expressed as s (singlet), d (doublet), t (triplet), q (quartet), p (pentet), quin (quintet), sept (septet), m (multiplet), or (br) broad, or a combination thereof. Coupling constant values ​​were given in Hz.

[0058] [General Procedure A] (General procedure A for Suzuki cross-coupling at the 3-position of 3-bromo-5-chlorothieno[3,2-b]pyridine)

[0059] [ka]

[0060] To a degassed solution (a mixture of 1,4-dioxane / H2O (4:1; 2.45 mL per 0.1 mmol of 3-bromo-5-chlorothieno[3,2-b]pyridine, in which 2.05 mmol of 3-bromo-5-chlorothieno[3,2-b]pyridine, 6.15 mmol of potassium phosphate, and 2.46 mmol of boronic acid or ester were dissolved), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.102 mmol) was added, and the reaction mixture was stirred at 110°C. The progress of the reaction was tracked by TLC. After the starting materials were consumed, the mixture was cooled to 25°C. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography.

[0061] (General procedure B for Suzuki cross-coupling at the 5-position of 3-substituted-5-chlorothieno[3,2-b]pyridine)

[0062] [ka]

[0063] To a degassed solution (a mixture of 1,4-dioxane / H2O (5:1; 0.95 mL per 0.1 mmol of 3-substituted-5-chlorothieno[3,2-b]pyridine, in which 0.650 mmol of 3-substituted-5-chlorothieno[3,2-b]pyridine, 1.95 mmol of potassium phosphate, and 0.780 mmol of boronic acid or ester were dissolved), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.031 mmol) was added, and the reaction mixture was stirred at 110°C (the progress of the reaction was tracked by TLC). After the starting materials were consumed, the mixture was cooled to 25°C. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography.

[0064] (General procedure C for Buchwald cross-coupling at the 5-position of 3-substituted-5-chlorothieno[3,2-b]pyridine)

[0065] [ka]

[0066] The reaction mixture was stirred at 110°C in a degassed solution (1 mL of 1,4-dioxane in which 0.203 mmol of 3-substituted-5-chlorothieno[3,2-b]pyridine, 0.312 mmol of cesium carbonate, 0.244 mmol of amine, and 0.008 mmol of tris(dibenzylideneacetone)dipalladium and 0.016 mmol of 4,5-bis(diphenylphosphin)-9,9-dimethylxanthene was dissolved). (The reaction was monitored by TLC). After the starting materials were consumed, the mixture was cooled to 25°C. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography.

[0067] (General procedure D for deprotection of N-Boc protected compounds) To the solution (0.098 mmol of each N-Boc protecting compound dissolved in 2 mL of methanol), 1.46 mL, 12.3 mmol of 4N HCl in dioxane was added, and the reaction mixture was stirred at 25°C (the progress of the reaction was tracked by TLC). After the starting materials were consumed, the mixture was cooled to 25°C. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography. After the predetermined reaction time, the solvent was evaporated. The crude product was dissolved in 2 mL of methanol, and the pH was adjusted to 8 using 0.25 mL of 7 M NH3 in methanol. The resulting solution was stirred for 30 minutes. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography or thin-layer chromatography for preparation.

[0068] (Preparation Example 1: 5-chloro-3-phenylthieno[3,2-b]pyridine (intermediate))

[0069] [ka]

[0070] The compound was prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (256 mg, 1.03 mmol) and 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane (231 mg, 1.13 mmol). Reaction temperature: 50°C. Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (hexane / siRNA, 100:0 to 90:10 gradient, followed by 100% hexane). The product was obtained as a pale yellow solid (273 mg, 55% yield).

[0071] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.14(d,J=8.4Hz,1H), 7.97(dd,J=8.3,1.2Hz,2 H), 7.87(s,1H), 7.49(t,J=7.6Hz,2H), 7.40(t,J=7.4Hz,1H), 7.32(d,J=8.4Hz,1H).

[0072] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 153.00, 149.03, 136.65, 133.79, 132.93, 132.83, 128.62, 128.38, 128.19, 127.98, 119.52.

[0073] HRMS theoretical value (C 13 H9ClNS)[M+H] + =246.0139, measured value [M+H] + = 246.0136.

[0074] FTIR (NEET), CM -1 :3094, 1598, 1561, 1517, 1482, 1379, 1143, 1122, 816, 797, 748, 717, 692, 643, 592, 558, 543.

[0075] (Preparation Example 2: 5-(1-methyl-1H-pyrazole-4-yl)-3-phenylthieno[3,2-b]pyridine)

[0076] [ka]

[0077] The compound was prepared according to general procedure B using 5-chloro-3-phenylthieno[3,2-b]pyridine (Preparation Example 1) (43 mg, 0.175 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (42 mg, 0.201 mmol). The mixture was reacted at 70°C for 1.5 hours, then cooled to 25°C and stirred for a further 1.5 hours. The solvent was evaporated, and the residue was purified twice by preparation TLC (hexane / siRNA, 50:50). The product was obtained as a white solid (25 mg, 49% yield).

[0078] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.16(d,J=8.4Hz,1H), 8.09(dd,J=8.2,1.1Hz,2H),8.0 4(s,1H), 7.99(s,1H), 7.83(s,1H), 7.55~7.46(m,3H), 7.40(t,J=7.4Hz,1H), 3.98(s,3H).

[0079] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.21, 149.50, 137.82, 136.76, 134.72, 13 1.62, 131.11, 129.09, 128.56, 128.37, 127.56, 126.94, 124.20, 115.42, 39.19.

[0080] HRMS theoretical value (C 17 H 14 N3S)[M+H] + =292.0903, measured value [M+H] + = 292.0902.

[0081] FTIR (NEET), CM -1 :3097, 2927, 1579, 1398, 1382, 1211, 1051, 810, 751, 721.

[0082] (Preparation Example 3: 4-(5-chlorothieno[3,2-b]pyridine-3-yl)benzonitrile (intermediate))

[0083] [ka]

[0084] The compound was prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (100 mg, 0.402 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (110 mg, 0.482 mmol). Reaction temperature: 50°C. Reaction time: 45 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 80:20 gradient). The product was obtained as a pale yellow solid (68 mg, 63% yield).

[0085] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.18(d,J=8.5Hz,1H), 8.14(d,J=8.5Hz,2H), 8.00(s,1H), 7.77(d,J=8.4Hz,2H), 7.37(d,J=8.5Hz,1H).

[0086] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.42, 149.41, 138.08, 134.44, 133.13, 132.87, 132.42, 130.17, 128.75, 120.07, 118.92, 111.37.

[0087] HRMS (APCI): Theoretical value (C 14 H8ClN2S)[M+H] + =271.0091, measured value [M+H] + = 271.0090.

[0088] FTIR (NEET), CM -1 :3096, 2224, 1604, 1563, 1534, 1378, 1146, 1131, 785, 553.

[0089] (Preparation Example 4: 4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)benzonitrile)

[0090] [ka]

[0091] The compound was prepared according to general procedure B using 4-(5-chlorothieno[3,2-b]pyridine-3-yl)benzonitrile (Preparation Example 3) (50 mg, 0.185 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (46 mg, 0.222 mmol). Reaction time: 75 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 70:30 to 0:100 gradient). The product was obtained as a white solid (50 mg, 86% yield).

[0092] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.25(d,J=8.5Hz,2H), 8.19(d,J=8.5Hz,1H), 8.03(s, 1H), 7.97(s,1H), 7.94(s,1H), 7.79(d,J=8.5Hz,2H), 7.52(d,J=8.5Hz,1H), 4.00(s,3H).

[0093] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.65, 149.90, 139.08, 137.80, 134.64, 13 2.18, 131.62, 131.32, 129.01, 128.87, 123.85, 119.10, 115.91, 110.89, 39.26.

[0094] HRMS (APCI): Theoretical value (C 18 H 13 N4S)[M+H] + =317.0855, measured value [M+H] + =317.0852.

[0095] FTIR (NEET), CM -1 :2975, 2925, 2224, 1604, 1579, 1379, 1214, 993, 852, 829, 817, 791, 560.

[0096] (Preparation Example 5: 5-chloro-3-(4-fluorophenyl)thieno[3,2-b]pyridine (intermediate))

[0097] [ka]

[0098] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (100 mg, 0.402 mmol) and (4-fluorophenyl)boronic acid (67 mg, 0.482 mmol) according to general procedure A. Reaction time: 45 minutes. The solvent was evaporated, and the residue was purified twice by flash chromatography (hexane / siRNA, 100:0 to 85:15 gradient; then hexane / siRNA, 100:0 to 97:3 gradient). The product was obtained as an impure white solid (71 mg, yield less than 67%). The product was used in the next step without further purification.

[0099] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.14~8.10(m,2H), 7.98~7.92(m,1H), 7.81(s,1H), 7.24~7.13(m,3H).

[0100] 13 C NMR(126MHz,Chloroform-d)δ(ppm)162.63(d,J=247.4Hz), 153.72, 149.04, 132.95, 132.73 (d,J=8.5Hz), 131.39, 129.99(d,J=8.1Hz), 127.90, 126.98, 119.56, 115.51(d,J=21.4Hz).

[0101] 19 F NMR (471MHz, Chloroform-d) δ(ppm) -113.9203.

[0102] HRMS (APCI): Theoretical value (C 13 H8ClFNS)[M+H] +=264.0045, measured value [M+H] + =264.0043.

[0103] (Preparation Example 6: 3-(4-fluorophenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0104] [ka]

[0105] The compound was prepared using 5-chloro-3-(4-fluorophenyl)thieno[3,2-b]pyridine (Preparation Example 5) (60 mg, 0.228 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (57 mg, 0.273 mmol) according to general procedure B. After 3 hours, additional potassium phosphate (48 mg, 0.228 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (24 mg, 0.113 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8.5 mg, 0.011 mmol) were added, and the mixture was refluxed for a further 1 hour. The solvent was evaporated, and the resulting residue was purified by flash chromatography (hexane / siRNA, 50:50 to 0:100 gradient). The product was obtained as a white solid (34 mg, 48% yield).

[0106] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.29(d,J=8.5Hz,1H), 8.19(s,1H), 8.18~8.12(m,2H) , 8.09~8.06(m,1H), 8.05(s,1H), 7.63(d,J=8.5Hz,1H), 7.25~7.19(m,2H), 3.96(s,3H).

[0107] 13C NMR(126MHz,Methanol-d4)δ(ppm)163.80(d,J=245.4Hz), 154.15, 150.79, 138.74, 136.42, 133.24, 132.70 , 132.41(d,J=3.5Hz), 131.32(d,J=8.0Hz), 131.03, 128.61, 125.32, 116.77, 116.05(d,J=21.7Hz), 39.09.

[0108] 19 F NMR(471MHz,Methanol-d4)δ(ppm)-117.0295.

[0109] HRMS (APCI): Theoretical value (C 17 H 13 FN3S)[M+H] + =310.0809, measured value [M+H] + = 310.0810.

[0110] FTIR (NEET), CM -1 :3097,2939,1576,1542,1526,1408,1397,1220,1209,1159,1015,993,830,785,734,653,563,548.

[0111] (Preparation Example 7: tert-butyl 4-(5-chlorothieno[3,2-b]pyridine-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate (intermediate))

[0112] [ka]

[0113] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (207 mg, 0.833 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (310 mg, 1.00 mmol) according to general procedure A. Reaction time: 2.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 80:20 gradient). The product was obtained as an impure white solid (215 mg, yield less than 74%). This product was used in the next step without further purification.

[0114] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.03(d,J=8.4Hz,1H), 7.52(s,1H), 7.23(d,J=8.4Hz,1H), 7.16(br s,1H), 4.15(q,J=2.5Hz,2H), 3.66(t,J=5.6Hz,2H), 2.77~2.47(m,2H), 1.48(s,9H).

[0115] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 154.73, 152.83, 148.35, 135.30, 132.79, 132.62, 128.75, 126.44, 124.19, 119.22, 79.50, 31.45, 28.40, 22.52, 13.99.

[0116] HRMS (APCI): Theoretical value (C 17 H 20 N2O2S)[M+H] + =350.0856, measured value [M+H] + = Not detected.

[0117] FTIR (NEET), CM -1 :2976, 2247, 1681, 1419, 1382, 1364, 1160, 1115, 987, 726, 646.

[0118] (Preparation Example 8: tert-butyl 4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate (intermediate))

[0119] [ka]

[0120] The compounds were prepared according to general procedure B using tert-butyl 4-(5-chlorothieno[3,2-b]pyridine-3-yl)-3,6-dihydropyridine-1(2H)-carboxylate (Preparation Example 7) (126 mg, 0.359 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (94 mg, 0.449 mmol). Reaction temperature: 85°C. Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 90:10 to 50:50 gradient). The product was obtained as an impure yellow waxy substance (63 mg, yield less than 44%). This product was used in the next step without further purification.

[0121] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.11(d,J=8.3Hz,1H), 8.02(s,1H), 7.96(s,1H), 7.52(s,1H), 7.45( d,J=8.4Hz,1H), 7.37(s,1H), 4.22(s,2H), 4.00(s,3H), 3.73(t,J=5.7Hz,2H), 2.73(s,2H), 1.51(s,9H).

[0122] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 154.95, 152.98, 148.95, 137.72, 135.91, 131.74, 131.52, 129.80, 129.26, 125.79, 123.71, 115.48, 79.61, 39.25, 28.54, 28.01, 24.86.

[0123] HRMS (APCI): Theoretical value (C 21 H 25 N4O2S)[M+H] + =397.1693, measured value [M+H] + = 397.1697.

[0124] FTIR (NEET), CM -1 :2976, 1685, 1579, 1420, 1402, 1366, 1115, 904, 728, 649.

[0125] (Preparation example 9: 5-(1-methyl-1H-pyrazole-4-yl)-3-(1,2,3,6-tetrahydropyridine-4-yl)-thieno[3,2-b]pyridine)

[0126] [ka]

[0127] To a solution (dissolved in 2 mL of dichloromethane, tert-butyl 4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)-3,6-di-hydropyridine-1(2H)-carboxylate (Preparation Example 8) (47 mg, 0.118 mmol)), trifluoroacetic acid (144 μL, 1.88 mmol) was added, and the reaction mixture was stirred at 25°C for 3 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (gradient of 7M NH3 in hexane / siRNA / methanol, 80:20:0:0 to 0:85:13:2; followed by a gradient of dichloromethane / methanol, 95:5 to 80:20). The product was obtained as a white solid (9 mg, 26%).

[0128] 1H NMR(500MHz,Methanol-d4)δ(ppm)8.28(d,J=8.5Hz,1H), 8.26(s,1H), 8.10(s,1H), 7.93(s,1H), 7.64(d,J=8.5Hz,1H), 7.57~7.54(m,1H), 4.00(br s,2H), 3.98(s,3H), (t,J=6.2Hz,2H), 3.04(br s,2H).

[0129] 13 C NMR(126MHz,Methanol-d4)δ(ppm)154.30, 150.71, 138.80, 135.04, 133.13, 132. 81, 131.28, 131.10, 128.95, 125.20, 119.61, 116.95, 43.52, 42.31, 39.12, 30.73.

[0130] HRMS (APCI): Theoretical value (C 16 H 17 N4S)[M+H] + =297.1168, measured value [M+H] + = 297.1171.

[0131] FTIR (NEET), CM -1 :3357, 2955, 2917, 2849, 1703, 1631, 1579, 1463, 1220, 1187, 1080, 967, 831, 820.

[0132] (Preparation Example 10: 5-chloro-3-(pyridine-3-yl)thieno[3,2-b]pyridine (intermediate))

[0133] [ka]

[0134] According to General Procedure A, the compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.805 mmol), pyridin-3-ylboronic acid (119 mg, 0.966 mmol), and triethylamine (0.66 mL) instead of potassium phosphate. Reaction time: 3 hours. The solvent was evaporated and the residue was purified by flash chromatography (hexane / EtOAc, gradient of 100:0 to 50:50). The product was obtained as a pale yellow solid (102 mg, 51% yield).

[0135] 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 9.11 (d, J = 1.4 Hz, 1H), 8.63 (dd, J = 4.8, 1.7 Hz, 1H), 8.41 (dt, J = 7.9, 2.0 Hz, 1H), 8.17 (d, J = 8.5 Hz, 1H), 7.96 (s, 1H), 7.43 (ddd, J = 7.9, 4.8, 0.9 Hz, 1H), 7.35 (d, J = 8.5 Hz, 1H).

[0136] 13 C NMR (126 MHz, Chloroform-d) δ (ppm) 152.77, 149.34, 149.03, 148.96, 135.62, 133.22, 133.05, 132.74, 129.74, 128.89, 123.45, 119.92.

[0137] HRMS calculated for (C 12 H8ClN2S) [M + H] + = 247.0091, found [M + H] + = 247.0090.

[0138] FTIR (neat), cm -1 : 3095, 3028, 1563, 1533, 1438, 1130, 780, 701, 450.

[0139] (Preparation Example 11: 5-(1-methyl-1H-pyrazol-4-yl)-3-(pyridin-3-yl)thieno[3,2-b]pyridine)

[0140]

Chem.

[0141] According to General Procedure B, a compound was prepared using 5-chloro-3-(pyridin-3-yl)thieno[3,2-b]pyridine (Preparation Example 10) (45 mg, 0.182 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (46 mg, 0.219 mmol). Reaction time: 8 hours. The solvent was evaporated and the residue was purified by flash chromatography (hexane / EtOAc, gradient from 90:10 to 0:100). The product was obtained as a white solid (43 mg, yield 82%).

[0142] 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 9.34 (d, J = 2.2 Hz, 1H), 8.63 (dd, J = 4.9, 1.7 Hz, 1H), 8.41 (dt, J = 7.7, 2.0 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H), 8.02 (s, 2H), 7.91 (s, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.44 (ddd, J = 8.0, 4.7, 0.9 Hz, 1H), 3.98 (s, 3H).

[0143] 13 C NMR (126 MHz, Chloroform-d) δ (ppm) 152.93, 149.87, 149.44, 148.51, 137.73, 135.58, 133.43, 131.48, 131.25, 130.59, 129.18, 127.72, 123.89, 123.32, 115.76, 39.22.

[0144] HRMS calculated value (C 16 H 13 N4S) [M + H] + = 293.0855, measured value [M + H] + = 293.0858.

[0145] FTIR (neat), cm -1:3076, 2923, 1579, 1397, 1369, 1224, 993, 826, 788, 619, 557.

[0146] (Preparation Example 12: 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0147] [ka]

[0148] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (400 mg, 1.61 mmol) and pyridine-4-ylboronic acid (237 mg, 1.93 mmol) according to general procedure A. Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 40:60 gradient). The product was obtained as a brown solid (632 mg, 80% yield).

[0149] 1 H NMR (500MHz Chloroform-d) δ(ppm) 8.72(dd,J=4.7,1.4Hz,2H), 8.17(d,J=8.4Hz,1H), 8.08(s,1H), 7.96(dd,J=4.5,1.7Hz,2H), 7.36(d,J=8.5Hz,1H).

[0150] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.50, 150.21, 149.39, 140.83, 133.51, 133.07, 132.88, 130.61, 122.40, 120.04.

[0151] HRMS theoretical value (C 12 H8ClN2S)[M+H] + =247.0091, measured value [M+H] + =247.0089.

[0152] FTIR (NEET), CM -1:3093, 1597, 1556, 1383, 1150, 1127, 793, 642, 548, 491.

[0153] (Preparation Example 13: 5-(1-methyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0154] [ka]

[0155] The compounds were prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (160 mg, 0.650 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (162 mg, 0.780 mmol). Reaction time: 1 hour. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, gradient of 80:20:0 to 0:95:5). The product was obtained as a white solid (172 mg, 90% yield).

[0156] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.73(dd,J=4.6,1.7Hz,2H)8.18(d,J=8.4Hz,1H),8.08(dd,J=4 .6,1.7Hz,2H).8.04(d,J=0.7Hz,1H), 8.03(s,1H), 8.00(s,1H), 7.52(d,J=8.5Hz,1H), 4.00(s,3H).

[0157] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.82, 150.00, 149.94, 141.82, 137.84, 133.72, 131.62, 131.27, 129.44, 129.06, 123.90, 122.65, 115.89, 39.25.

[0158] HRMS theoretical value (C16 H 13 N4S)[M+H] + =293.0855, measured value [M+H] + =293.0857.

[0159] FTIR (NEET), CM -1 :3076,2923,1595,1579,15487,1510,1397,1369,1308,1224,1171,1052,993,981,826,788,721,699,638,619,589,557.

[0160] (Preparation Example 14: 5-Chloro-3-(2-methylpyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0161] [ka]

[0162] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (250 mg, 1.01 mmol) and (2-methylpyridine-4-yl)boronic acid (166 mg, 1.21 mmol) according to general procedure A. Reaction time: 48 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10 to 50:50 gradient). The product was obtained as a white solid (39 mg, 15% yield).

[0163] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.61(d,J=5.1Hz,1H), 8.17(d,J=8.5Hz,1H),8. 06(s,1H), 7.81(s,1H), 7.78(d,J=5.0Hz,1H), 7.36(d,J=8.54Hz,1H), 2.67(s,3H).

[0164] 13C NMR (126MHz, Chloroform-d) δ (ppm) 158.67, 152.58, 149.40, 149.32, 141.41, 133.83, 133.07, 132.87, 130.55, 122.03, 120.03, 119.77, 24.56.

[0165] HRMS (APCI): Theoretical value (C 13 H 10 ClN2S)[M+H] + =261.0248, measured value [M+H] + = 261.0251.

[0166] FTIR (NEET), CM -1 :2954, 2922, 2852, 1602, 1560, 1531, 1380, 1146, 1146, 1124, 967, 847, 833, 794, 707, 658.

[0167] (Preparation Example 15: 5-(1-methyl-1H-pyrazole-4-yl)-3-(2-methylpyridine-4-yl)thieno[3,2-b]pyridine)

[0168] [ka]

[0169] The compounds were prepared according to general procedure B using 5-chloro-3-(2-methylpyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 14) (35 mg, 0.134 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (35 mg, 0.168 mmol). Reaction temperature: 85°C. Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 70:30:0 to 0:90:10 gradient). The product was obtained as a white solid (29 mg, 71% yield).

[0170] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.62(d,J=5.3Hz,1H), 8.16(d,J=8.4Hz,1H), 8.04(s,1H), 8.00(s, 1H), 7.97(s,1H), 7.95(s,1H), 7.89(d,J=5.3Hz,1H), 7.50(d,J=8.5Hz,1H), 3.99(s,3H), 2.67(s,3H).

[0171] 13 C NMR(126MHz,Chloroform-d)δ(ppm)158.37, 152.86, 149.84, 149.08, 142.25, 137.85, 1 33.88, 131.59, 131.23, 129.32, 128.98, 123.92, 122.22, 119.92, 115.81, 39.24, 24.57.

[0172] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1015.

[0173] FTIR (NEET), CM -1 :3096, 2923, 1603, 1578, 1537, 1376, 1215, 1167, 984, 834, 790, 700, 655.

[0174] (Preparation Example 16: 5-chloro-3-(2-methoxypyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0175] [ka]

[0176] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (250 mg, 1.01 mmol) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (185 mg, 1.21 mmol) according to general procedure A. Reaction time: 21 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 90:10 gradient). The product was obtained as a white solid (154 mg, 55% yield).

[0177] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.27(d,J=5.3Hz,1H), 8.16(d,J=8.5Hz,1H), 8.05 (s,1H), 7.51(dd,J=5.4,1.4Hz,1H), 7.48(s,1H), 7.35(d,J=8.5Hz,1H), 4.01(s,3H).

[0178] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 164.76, 152.57, 149.38, 147.05, 143.56, 133.67, 133.02, 132.84, 130.57, 120.00, 116.05, 109.57, 53.60.

[0179] HRMS (APCI): Theoretical value (C 13 H 10 ClN2OS)[M+H] + =277.0197, measured value [M+H] + = 277.0199.

[0180] FTIR (NEET), CM -1 :3085, 1606, 1552, 1479, 1373, 1327, 1307, 1204, 1165, 1152, 1056, 1042, 977, 886, 849, 795, 735, 719, 651, 457, 448.

[0181] (Preparation Example 17: 3-(2-methoxypyridine-4-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0182] [ka]

[0183] The compound was prepared according to general procedure B using 5-chloro-3-(2-methoxypyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 16) (50 mg, 0.181 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (47 mg, 0.226 mmol). Reaction temperature: 85°C. Reaction time: 3.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a white solid (56 mg, 96% yield).

[0184] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.28(d,J=5.3Hz,1H), 8.17(d,J=8.44,1H), 8.00(s,1H), 8.00(d ,J=2.7Hz,2H), 7.66(s,1H), 7.61(d,J=5.2Hz,1H), 7.51(d,J=8.5Hz,1H), 4.03(s,3H), 4.00(s,3H).

[0185] 13 C NMR(126MHz,Chloroform-d)δ(ppm)164.76, 152.87, 149.88, 146.67, 144.48, 137.86, 1 33.72, 131.58, 131.21, 129.44, 129.13, 123.91, 116.26, 115.81, 109.69, 53.58, 39.27.

[0186] HRMS (APCI): Theoretical value (C 17 H 15 N4OS)[M+H] +=323.0961, measured value [M+H] + =323.0963.

[0187] FTIR (NEET), CM -1 :2942, 1604, 1577, 1536, 1481, 1458, 1393, 1374, 1328, 1306, 1281, 1214, 1197, 1164, 1054, 1041, 996, 838, 819, 789, 724, 651, 612.

[0188] (Preparation Example 18: 4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-ol)

[0189] [ka]

[0190] Concentrated hydrochloric acid (0.7 mL) was added to 3-(2-methoxypyridine-4-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 17) (16 mg, 0.048 mmol), and the reaction mixture was stirred at 120°C for 2 hours. The reaction was quenched to pH 7 with 6 M NaOH and extracted with ethyl acetate (2 × 10 mL). The integrated organic extract was washed with saline solution (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (dichloromethane / methanol, gradient from 100:0 to 85:15). The product was obtained as a white solid (7 mg, 47%).

[0191] 1 H NMR(500MHz,DMSO-d6)δ(ppm)11.51(br s,1H), 8.64(s,1H), 8.51(d,J=8.5Hz,1H), 8.33(s,1H), 8.08(s,1H), 7.74(d,J=8.4Hz,1H), 7.49(s 1H), 7.46(d,J=6.9Hz,1H), 7.01(dd,J=6.9,1.8Hz,1H), 3.93(s,3H).

[0192] 13 C NMR(126MHz,DMSO-d6)δ(ppm)162.79, 152.26, 149.56, 145.31, 137.31, 134.71, 1 32.45, 132.22, 131.50, 131.04, 129.61, 122.86, 117.23, 115.90, 104.71, 38.78.

[0193] HRMS (APCI): Theoretical value (C 16 H 13 N4OS)[M+H] + =309.0805, measured value [M+H] + =309.0803.

[0194] FTIR (NEET), CM -1 :3383, 3089, 2929, 1641, 1579, 1566, 1541, 1493, 1434, 1216, 990, 982, 808, 786, 509, 429.

[0195] (Preparation Example 19: 4-(5-chlorothieno[3,2-b]pyridine-3-yl)picolinonitrile (intermediate))

[0196] [ka]

[0197] The compound was prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (25 mg, 0.100 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-picolinenitrile (29 mg, 0.125 mmol). Reaction temperature: 80°C. Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 70:30 gradient). The product was obtained as a white solid (24 mg, 89% yield).

[0198] 1H NMR (500MHz, Chloroform-d) δ(ppm) 8.82(d,J=5.1Hz,1H), 8.45~8.38(m,1H), 8.27(dd,J=5.2,1.7Hz,1H), 8.22(s,1H), 8.20(s,1H), 7.42(d,J=8.5Hz,1H).

[0199] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.03, 151.51, 149.87, 142.19, 134.48, 133.27, 132.90, 132.00, 131.21, 127.05, 125.22, 120.61, 117.43.

[0200] HRMS (APCI): Theoretical value (C 13 H7ClN3S)[M+H] + =272.0044, measured value [M+H] + =272.0046.

[0201] FTIR (NEET), CM -1 :3094, 2924, 2239, 1596, 1564, 1550, 1379, 1148, 1115, 992, 868, 849, 664.

[0202] (Preparation Example 20: 4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)picolinonitrile)

[0203] [ka]

[0204] The compound was prepared according to general procedure B using 4-(5-chlorothieno[3,2-b]pyridine-3-yl)picolinonitrile (Preparation Example 19) (24 mg, 0.086 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (22 mg, 0.108 mmol). Reaction temperature: 75°C. Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a white solid (9 mg, 34% yield).

[0205] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.81(d,J=5.2Hz,1H), 8.67(dd,J=1.9,0.8Hz,1H), 8.29(dd,J=5.2,1. 8Hz,1H), 8.22(d,J=8.5Hz,1H), 8.14(s,1H), 8.05(s,1H), 8.02(s,1H), 7.57(d,J=8.5Hz,1H), 4.03(s,3H).

[0206] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.34, 151.25, 150.34, 143.13, 137.76, 134.27, 13 1.65, 131.53, 131.31, 130.92, 129.18, 127.46, 125.24, 123.56, 117.63, 116.38, 39.37.

[0207] HRMS (APCI): Theoretical value (C 17 H 12 N5S)[M+H] + =318.0808, measured value [M+H] + = 318.0810.

[0208] FTIR (NEET), CM -1 :2924, 2853, 1726, 1595, 1578, 1464, 1426, 1377, 1262, 1129.

[0209] (Preparation Example 21: 5-chloro-3-(2-fluoropyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0210] [ka]

[0211] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (130 mg, 0.523 mmol) and 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (88 mg, 0.630 mmol). Reaction time: 3 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (cyclohexane / siRNA, 80:20 to 60:40 gradient; then cyclohexane / siRNA, 95:5 to 50:50 gradient). The product was obtained as an impure white solid (64 mg, yield less than 32%). The product was used in the next step without further purification.

[0212] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.32(d,J=5.3Hz,1H), 8.19(d,J=8.5Hz,1H ), 8.14(s,1H), 7.85(dt,J=5.2,1.7Hz,1H), 7.72(s,1H), 7.39(d,J=8.5Hz,1H).

[0213] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 164.39 (d, J = 237.6 Hz), 152.27, 149.62, 148.92 (d, J = 15.2 Hz), 147.89 (d, J=15.2Hz), 133.15, 132.87, 132.35(d,J=3.6Hz), 131.46, 120.31, 120.10(d,J=4.1Hz), 108.08(d,J=39.0Hz).

[0214] 19F NMR (471MHz, Chloroform-d) δ (ppm) -67.4964.

[0215] HRMS (APCI): Theoretical value (C 12 H7ClFN2S)[M+H] + =264.9997, measured value [M+H] + = 265.0001.

[0216] FTIR (NEET), CM -1 :3079, 1612, 1562, 1378, 1146, 1123, 992, 850, 835, 812, 652, 564.

[0217] (Preparation Example 22: 3-(2-fluoropyridine-4-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0218] [ka]

[0219] The compound was prepared according to general procedure B using 5-chloro-3-(2-fluoropyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 21) (64 mg, 0.242 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (60 mg, 0.290 mmol). Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10 to 50:50 gradient). The product was obtained as a white solid (48 mg, 64% yield).

[0220] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.31(d,J=5.2Hz,1H), 8.17(d,J=8.5Hz,1H), 8.07(s,1H), 8 .03(s,1H), 7.99(s,1H), 7.94(s,1H), 7.88(d,J=5.2Hz,1H), 7.52(d,J=8.5Hz,1H), 4.00(s,3H).

[0221] 13 C NMR(126MHz,Chloroform-d)δ(ppm)164.37(d,J=236.9Hz), 152.55, 150.10, 147.48(d,J=15.5Hz), 147.01(d,J=9.0Hz), 1 37.81, 132.36(d,J=3.6Hz), 131.56, 131.32, 130.33, 129.10, 123.71, 120.12(d,J=3.9Hz), 116.06, 108.13(d,J=39.2Hz). 39.28.

[0222] 19 F NMR(471MHz,Chloroform-d)δ(ppm)-68.0315 HRMS (APCI): Theoretical value (C 16 H 12 FN4S)[M+H] + =311.0761, measured value [M+H] + =311.0758.

[0223] FTIR (NEET), CM -1 :3058, 1607, 1577, 1552, 1513, 1475, 1398, 1377, 1214, 1158, 992, 972, 887, 828, 807, 791, 699, 648, 612, 547, 489, 455, 420.

[0224] (Preparation Example 23: tert-butyl(4-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)-carbamate (intermediate))

[0225] [ka]

[0226] The compound was prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (150 mg, 0.603 mmol), tert-butyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)carbamate (232 mg, 0.724 mmol), and triethylamine (300 μL, 2.20 mmol) instead of potassium phosphate. Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, gradient from 100:0 to 80:20). The product was obtained as a white solid (158 mg, 79% yield).

[0227] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.41(dd,J=1.6,0.8Hz,1H), 8.37(dd,J=5.2,0.8Hz,1H), 8.17~8.14(m,2H), 7.86(dd,J=5.3,1.6Hz,1H), 7.59(br s,1H), 7.35(d,J=8.5Hz,1H), 1.55(s,9H).

[0228] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.65,152.46,152.39,149.36,148.31,1 43.12,133.97,133.03,132.84,131.14,119.92,117.96,110.66,81.02,28.33.

[0229] HRMS (APCI): Theoretical value (C 17 H 17 ClN3O2S)[M+H] + =362.0725, measured value [M+H] + =362.0723.

[0230] FTIR (NEET), CM -1:2977, 1715, 1608, 1565, 1381, 1293, 1160, 1124, 844, 810, 766, 736, 658.

[0231] (Preparation Example 24: tert-butyl(4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-yl)carbamate)

[0232] [ka]

[0233] The compound was prepared according to general procedure B using tert-butyl(4-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)carbamate (Preparation Example 22) (100 mg, 0.276 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (69 mg, 0.331 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 0:100 gradient). The product was obtained as a white solid (52 mg, 46% yield).

[0234] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.09(s,1H), 8.45(s,1H), 8.36~8.31(m,1H), 8.17(d,J=8.5Hz,1H), 8.11(s,1 H), 8.08~8.03(m,1H), 7.76(s,1H), 7.62(dd,J=5.3,1.5Hz,1H), 7.54(d,J=8.5Hz,1H), 3.99(s,3H), 1.60(s,9H).

[0235] 13C NMR(126MHz,Chloroform-d)δ(ppm)152.93, 152.50, 152.44, 150.24, 147.81, 143.87, 137.78, 1 33.63, 131.56, 131.21, 130.11, 129.80, 124.03, 117.37, 115.87, 111.04, 80.65, 39.22, 28.39.

[0236] HRMS (APCI): Theoretical value (C 21 H 22 N5O2S)[M+H] + =408.1489, measured value [M+H] + = 408.1488.

[0237] FTIR (NEET), CM -1 :2976, 1720, 1606, 1579, 1539, 1271, 1220, 1159, 731.

[0238] (Preparation Example 25: 4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-amine)

[0239] [ka]

[0240] The compound was prepared using tert-butyl(4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-yl)carbamate (Preparation Example 24) (40 mg, 0.098 mmol) according to general procedure D. Reaction time: 6 hours. The solvent was evaporated, and the residue was purified by preparation TLC (dichloromethane / methanol / 7M NH3 in methanol, 93:5:2; followed by siRNA, 100%). The product was obtained as a pale yellow solid (13 mg, yield 43%).

[0241] 1H NMR(500MHz,Methanol-d4)δ(ppm)8.31(d, J=8.5Hz, 1H), 8.29(s, 1H), 8.27(s, 1H), 8.15~8.10(m, 1H), 7.99 (dd, J=5.6, 0.5Hz,1H), 7.66(d,J=8.5Hz,1H), 7.60~7.58(m,1H), 7.35(dd,J=5.6,1.5Hz,1H), 3.98(s,3H).

[0242] 13 C NMR(126MHz,Methanol-d4)δ(ppm)161.04, 154.09, 151.11, 147.53, 145.51, 138.88 , 134.79, 133.28, 132.80, 131.58, 131.25, 125.21, 117.04, 113.66, 109.24, 39.11.

[0243] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + =308.0964, measured value [M+H] + =308.0964.

[0244] FTIR (NEET), CM -1 :2284, 2093, 2045, 1606, 1577, 1536, 1421, 1399, 1215, 1169, 992, 865~792, 665.

[0245] (Preparation Example 26: tert-butyl((4-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)-methyl)carbamate (intermediate))

[0246] [ka]

[0247] Following general procedure A, the compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (496 mg, 1.99 mmol), tert-butyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)methyl)carbamate (800 mg, 2.39 mmol), and triethylamine (1.3 mL, 9.33 mmol) instead of potassium phosphate. After 3 hours, an additional triethylamine (0.2 mL, 1.44 mmol) was added, and the mixture was refluxed for a further 5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 0:100 gradient). The product was obtained as a pale yellow solid (679 mg, 91% yield).

[0248] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.64(dd,J=5.2,0.6Hz,1H), 8.17(d,J=8.5Hz,1H), 8.08(s,1H), 7.91( dd,J=5.2,1.3Hz,1H), 7.88(s,1H), 7.36(d,J=8.5Hz,1H), 5.66(s,1H), 4.53(d,J=5.3Hz,2H), 1.47(s,9H).

[0249] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 157.88, 156.04, 152.50, 149.54, 149.43, 141. 67, 133.48, 133.08, 132.85, 130.81, 121.19, 120.41, 120.07, 75.01, 45.95, 28.43.

[0250] HRMS (APCI): Theoretical value (C 18 H 19 ClN3O2S)[M+H] + =376.0881, measured value [M+H] + = 376.0878.

[0251] FTIR (NEET), CM -1:3343, 2977, 1697, 1604, 1509, 1381, 1366, 1247, 1164, 1146, 1126, 849, 731, 658.

[0252] (Preparation Example 27: (4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-yl)methanamine)

[0253] [ka]

[0254] Following general procedure B, the compound was prepared using (4-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)methaneamine (Preparation Example 26) (80 mg (0.213 mmol)), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (53 mg, 0.256 mmol), and triethylamine (90 μL, 0.256 mmol) instead of potassium phosphate. After 2 hours, an additional triethylamine (1 mL, 7.17 mmol) and [1,1'-bis(diphenyl [Phosphino)ferrocene]dichloropalladium(II) (15 mg, 0.017 mmol) and tripotassium phosphate (45 mg, 0.213 mmol) were added, and the reaction mixture was refluxed for a further 7 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, gradient from 80:20:0 to 95:0:5) and TLC for preparation (siRNA, single elution; then cyclohexane / siRNA, 60:40, single elution). The product was obtained as a white solid (32 mg, 36% yield).

[0255] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.65(dd,J=5.2,0.8Hz,1H), 8.18(d,J=8.5Hz,1H), 8.15(s,1H), 8.11(s,1H), 8.03(s,1H), 8.02 (d,J=0.7Hz,1H), 7.94(dd,J=5.2,1.7Hz,1H), 7.53(d,J=8.5Hz,1H), 5.60(s,1H), 4.57(d,J=5.6Hz,2H), 4.02(s,3H), 1.45(s,9H).

[0256] 13 C NMR(126MHz,Chloroform-d)δ(ppm)157.76, 156.05, 152.81, 150.07, 149.27, 142.60, 137.72, 133. 59, 131.56, 131.28, 129.57, 129.44, 123.76, 121.29, 120.85, 115.89, 79.45, 46.15, 39.25, 28.41.

[0257] HRMS (APCI): Theoretical value (C 22 H 24 N5O2S)[M+H] + =422.1645, measured value [M+H] + = 422.1643.

[0258] FTIR (NEET), CM -1 :2976, 1698, 1602, 1578, 1365, 1266, 1246, 1163, 1048, 859, 791, 732, 699, 654.

[0259] (Preparation Example 28: (4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-yl)methanamine)

[0260] [ka]

[0261] The compound was prepared using (4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-yl)methanamine (Preparation Example 27) (18 mg, 0.047 mmol) according to general procedure D. After reacting at 25°C for 1 hour, additional 4N HCl in dioxane (68 μL, 0.188 mmol) and methanol (1 mL) were added, and the reaction mixture was stirred at 40°C for a further 5 hours. The solvent was evaporated, and the residue was purified by preparation TLC (dichloromethane / methanol / 7M NH3 in methanol, 88:10:2, eluted twice). The product was obtained as a brown solid (11 mg, yield 73%).

[0262] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.75(dd,J=5.2,0.9Hz,1H), 8.50(s,1H), 8.38(d,J=8.5Hz,1H), 8.35(s,1H), 8.32(dd,J=5.3,1.8Hz,1H), 8.28(s,1H), 8.13(d,J=0.7Hz,1H), 7.71(d,J=8.5Hz,1H), 4.41(s,2H), 3.99(s,3H).

[0263] 13 C NMR(126MHz,Methanol-d4)δ(ppm)153.87, 153.80, 151.33, 150.75, 144.76, 138.91, 13 3.52, 133.38, 133.05, 132.73, 131.19, 125.12, 123.54, 122.07, 117.40, 44.42, 39.17.

[0264] HRMS (APCI): Theoretical value (C 17 H 16 N5S)[M+H] + =322.1121, measured value [M+H] + = 322.1123.

[0265] FTIR (NEET), CM -1 :3608~3174, 3058, 1606, 1580, 1445, 1216, 996, 836, 814, 655.

[0266] (Preparation Example 29: 5-Chloro-3-(2,6-dimethylpyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0267] [ka]

[0268] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (140 mg, 0.563 mmol) and 2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (158 mg, 0.676 mmol). Reaction time: 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 85:15 to 50:50 gradient). The product was obtained as a white solid (80 mg, 52% yield).

[0269] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.16 (d, J = 8.4 Hz, 1H), 8.02 (s, 1H), 7.59 (s, 2H), 7.35 (d, J = 8.5Hz, 1H), 2.63 (s, 6H).

[0270] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 158.02, 152.66, 149.34, 141.64, 134.23, 133.03, 132.83, 130.33, 119.95, 119.24, 24.60.

[0271] HRMS (APCI): Theoretical value (C 14 H 12 ClN2S)[M+H] + =275.0404, measured value [M+H] + =275.0405.

[0272] FTIR (NEET), CM -1:2919, 1605, 1560, 1378, 1142, 1123, 842, 794, 734, 700, 564, 446.

[0273] (Preparation Example 30: 3-(2,6-dimethylpyridine-4-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno-[3,2-b]pyridine)

[0274] [ka]

[0275] The compound was prepared according to general procedure B using 5-chloro-3-(2,6-dimethylpyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 29) (72 mg, 0.260 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (67 mg, 0.325 mmol). Reaction temperature: 85°C. Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 80:20:0 to 0:90:10 gradient). The product was obtained as a white solid (81 mg, 98% yield).

[0276] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.17(d,J=8.5Hz,1H), 8.06(s,1H), 8.00(s, 1H), 7.96(s,1H), 7.78(s,2H), 7.51(d,J=8.5Hz,1H), 3.99(s,3H), 2.66(s,6H).

[0277] 13 C NMR(126MHz,Chloroform-d)δ(ppm)157.53, 152.93, 149.78, 142.78, 137.91, 1 34.05, 131.60, 131.25, 129.30, 128.92, 123.97, 119.57, 115.79, 39.27, 24.40.

[0278] HRMS (APCI): Theoretical value (C 18 H 17 N4S)[M+H] + =321.1168, measured value [M+H] + = 321.1172.

[0279] FTIR (NEET), CM -1 :1603, 1573, 1538, 1396, 1369, 1210, 1162, 1062, 978, 896, 853, 809, 714, 700, 689, 652, 618, 590, 548, 489, 416.

[0280] (Preparation Example 31: 5-chloro-3-(3-methylpyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0281] [ka]

[0282] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (100 mg, 0.402 mmol) and 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (114 mg, 0.483 mmol). Reaction time: 3 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (cyclohexane / siRNA, 90:10 to 30:70 gradient). The product was obtained as a brown solid (73 mg, 69% yield).

[0283] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.58(s,1H), 8.52(d,J=4.9Hz,1H), 8.18(d,J= 8.5Hz,1H), 7.76(d,J=2.2Hz,1H), 7.35(s,1H), 7.33(d,J=2.4Hz,1H), 2.28(s,3H).

[0284] HRMS (APCI): Theoretical value (C 13 H 10ClN2S)[M+H] + =261.0248, measured value [M+H] + = 261.0245.

[0285] FTIR (NEET), CM -1 :3425, 2978, 2924, 2852, 1599, 1563, 1465, 1379, 1143, 1124, 1111, 948, 883, 829.

[0286] (Preparation Example 32: 5-(1-methyl-1H-pyrazole-4-yl)-3-(3-methylpyridine-4-yl)thieno[3,2-b]pyridine)

[0287] [ka]

[0288] The compound was prepared according to general procedure B using 5-chloro-3-(3-methylpyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 31) (62 mg, 0.237 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (59 mg, 0.284 mmol). Reaction time: 5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 0:100 gradient). The product was obtained as a white solid (20 mg, 28% yield).

[0289] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.61(s,1H), 8.55(s,1H), 8.19(d,J=8.5Hz,1H), 7.94(s, 1H), 7.88(s,1H), 7.73(s,1H), 7.51(d,J=11.5Hz,1H), 7.50(s,1H), 3.94(s,3H), 2.35(s,3H).

[0290] 13C NMR(126MHz,Chloroform-d)δ(ppm)153.13, 150.07, 150.01, 145.90, 137.63, 1 34.89, 131.14, 130.72, 129.65, 129.12, 125.52, 123.74, 115.80, 39.19, 17.86.

[0291] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1012.

[0292] FTIR (NEET), CM -1 :2924, 1579, 1398, 1361, 1212, 995, 810, 651, 602.

[0293] (Preparation Example 33: 4-(5-chlorothieno[3,2-b]pyridine-3-yl)nicotinonitrile (intermediate))

[0294] [ka]

[0295] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (250 mg, 1.00 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (276 mg, 1.20 mmol) according to general procedure A. Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 95:5 to 70:30 gradient). The product was obtained as a white solid (69 mg, 25% yield).

[0296] 1H NMR (500MHz, Chloroform-d) δ(ppm) 9.01(s,1H), 8.91(d,J=5.2Hz,1H), 8.44(s,1H), 8.23(d,J=8.4Hz,1H), 8.10(d,J=5.3Hz,1H), 7.42(d,J=8.5Hz,1H).

[0297] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 153.85, 152.74, 152.13, 149.89, 143.89, 134.18, 133.24, 132.41, 129.91, 124.66, 120.68, 116.85, 108.76.

[0298] HRMS (APCI): Theoretical value (C 13 H7ClN3S)[M+H] + =272.0044, measured value [M+H] + = 272.0041.

[0299] FTIR (NEET), CM -1 :2978, 1602, 1587, 1564, 1539, 1507, 1490, 1380, 1229, 1158, 1145, 1125, 949, 835, 810, 792, 701, 563.

[0300] (Preparation Example 34: 4-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)nicotinonitrile)

[0301] [ka]

[0302] The compounds were prepared according to general procedure B using 4-(5-chlorothieno[3,2-b]pyridine-3-yl)nicotinonitrile (Preparation Example 33) (18 mg, 0.066 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (16 mg, 0.079 mmol), and instead of dioxane, SPhosPdG3 (7 mg, 0.007 mmol) and Sphos (3 mg, 0.007 mmol) were used instead of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dissolved in acetonitrile (0.3 mL). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient) and TLC for preparation (dichloromethane / methanol, 98:2). The product was obtained as a pale yellow solid (5 mg, 22% yield).

[0303] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.02(s,1H), 8.91(d,J=5.3Hz,1H), 8.35(s,1H), 8.22(d,J= 8.5Hz,1H), 8.17(d,J=5.2Hz,1H), 8.00(s,1H), 7.95(s,1H), 7.55(d,J=8.5Hz,1H), 3.98(s,3H).

[0304] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.93, 152.31, 152.23, 150.29, 144.83, 137.84, 13 2.93, 131.38, 131.07, 130.39, 129.16, 124.88, 123.55, 117.14, 116.51, 108.99, 39.26.

[0305] HRMS (APCI): Theoretical value (C 17 H 12 N5S)[M+H] + =318.0808, measured value [M+H] + = 318.0807.

[0306] FTIR (NEET), CM -1 :1579, 1403, 1215, 996, 822.

[0307] (Preparation Example 35: 5-chloro-3-(3-fluoropyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0308] [ka]

[0309] Following general procedure A, the compounds were prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (25 mg, 0.100 mmol), (3-fluoropyridine-4-yl)boronic acid (18 mg, 0.125 mmol), trimethylamine (27 μL, 0.200 mmol), and TPGS / 750-M (2% w) (1.2 mL), dissolved in THF (0.8 mL) instead of dioxane. The reactions were incubated at 40°C for 6 hours, followed by reflux for 6 hours. The reaction mixture was quenched with water (15 mL) and extracted with pharmaceutically acceptable ammonium compounds (2 × 15 mL). The integrated organic extract was washed with saline solution (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. After evaporation, the residue was purified by flash chromatography (hexane / pharmaceutically acceptable ammonium compounds, 100:0 to 80:20 gradient). The product was obtained as a pale yellow solid (10 mg, 39% yield).

[0310] 1 H NMR (500MHz, Chloroform-d) δ(ppm)8.72~8.68(m,1H), 8.63(d,J=15.6Hz,2H), 8.45(d,J=1.01,1H), 8.22(d,J=8.4Hz,1H), 7.42(d,J=8.5,1H).

[0311] 13C NMR (126MHz, Chloroform-d) δ (ppm) 157.97 (d, J=237.9Hz), 152.63, 149.69, 143.67 (d, J=5.3Hz), 13 6.42(d, J=29.2Hz), 135.77(d, J=11.4Hz), 133.17, 132.03, 130.98(app.s), 125.53, 125.07, 120.47.

[0312] 19 F NMR(471MHz,Chloroform-d)δ-127.3514 HRMS (APCI): Theoretical value (C 12 H7ClFN2S)[M+H] + =264.9997, measured value [M+H] + = 264.9999.

[0313] FTIR (NEET), CM -1 :1606, 1562, 1533, 1380, 1144, 1125, 842, 798, 701.

[0314] (Preparation Example 36: 3-(3-fluoropyridine-4-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0315] [ka]

[0316] The compound was prepared according to general procedure B using 5-chloro-3-(3-fluoropyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 35) (58 mg, 0.219 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (57 mg, 0.274 mmol). The reaction was carried out at 25°C for 40 minutes, and then the reaction was stirred at 75°C for a further 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 20:80 gradient). The product was obtained as a white solid (55 mg, 81% yield).

[0317] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.67~8.42 (m, 3H), 8.23 ​​(s, 1H), 8.15 (d, J=8.5Hz, 1H), 8.00 (s, 1H), 7.93 (s, 1H), 7.48 (d, J = 8.4Hz, 1H), 3.96 (s, 3H).

[0318] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 157.05 (d, J=258.2Hz), 152.98, 149.82, 145.46 (d, J=5.1Hz), 138.52 (d, J=26.2Hz), 137.76, 133.01 (d, J=10.2Hz), 131.10, 130.61, 129.19 (d, J=9.7Hz), 128.96, 126.59, 124.66 (br s), 123.73, 115.83, 39.18.

[0319] 19 F NMR(471MHz,Chloroform-d)δ(ppm)-130.0085.

[0320] HRMS (APCI): theoretical value (C 16 H 12 FN4S)[M+H + =311.0761,test value[M+H] + =311.0764.

[0321] FTIR(ニート)、cm -1 :3380, 2927, 1605, 1579, 1544, 1477, 1401, 1382, 1215, 1061, 1027, 994, 955, 834, 795, 640, 582, 469.

[0322] (Preparation Example 37: 5-クロロ-3-(ピリミジン-5-イル)チエノ[3,2-b]ピリジン (intermediate))

[0323]

change

[0324] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (224 mg, 0.901 mmol) and pyrimidine-5-ylboronic acid (134 mg, 1.08 mmol) according to general procedure A. Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 80:20 to 0:100 gradient). The product was obtained as a white solid (95 mg, 43% yield).

[0325] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 9.37 (s, 2H), 9.25 (s, 1H), 8.20 (d, J = 8.5 Hz, 1 H), 8.05 (s, 1 H), 7.39 (d, J = 8.5 Hz, 1 H).

[0326] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 157.67, 155.75, 152.38, 149.76, 133.14, 132.62, 129.93, 129.70, 127.92, 120.37.

[0327] HRMS theoretical value (C 11 H7ClN3S)[M+H] + 248.0044, measured value [M+H] + =248.0047.

[0328] FTIR (NEET), CM -1 :1562, 1530, 1405, 1378, 1347, 1195, 1139, 1126, 1115, 846, 826, 799, 765, 717, 684, 634, 483.

[0329] (Preparation Example 38: 5-(1-methyl-1H-pyrazole-4-yl)-3-(pyrimidine-5-yl)thieno[3,2-b]pyridine)

[0330] [ka]

[0331] The compound was prepared according to general procedure B using 5-chloro-3-(pyrimidine-5-yl)thieno[3,2-b]pyridine (Preparation Example 37) (35 mg, 0.141 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (35 mg, 0.170 mmol). After 16 hours, triethylamine (0.7 mL, 5.04 mmol) was added, and the mixture was refluxed for a further 36 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient). The product was obtained as a white solid (30 mg, 72% yield).

[0332] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.49(s,2H), 9.24(s,1H), 8.21(d,J=8.5Hz ,1H), 8.03(d,J=14.3Hz,2H), 8.00(s,1H), 7.56(d,J=8.5Hz,1H), 3.99(s,3H).

[0333] 13 C NMR(126MHz,Chloroform-d)δ(ppm)157.28, 155.82, 152.57, 150.24, 137.69, 13 6.91, 131.37, 131.32, 129.98, 129.29, 128.71, 128.42, 123.58, 116.09, 39.24.

[0334] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H] + =294.0808, measured value [M+H] + =294.0806.

[0335] FTIR (NEET), CM -1 :2920, 2851, 1584, 1555, 1402, 1219, 995, 817, 794, 723, 649, 615.

[0336] (Preparation example 39: 5-chloro-3-(pyridazine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0337] [ka]

[0338] Compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (170 mg, 0.684 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridazine (175 mg, 0.850 mmol), and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (22 mg, 0.034 mmol) instead of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II). Reaction temperature: 70°C. Reaction time: 16 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (cyclohexane / siRNA, 80:20 to 20:80 gradient; then dichloromethane / methanol, 100:0 to 95:5 gradient). The product was obtained as a white solid (110 mg, 65% yield).

[0339] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.76(dd,J=2.4,1.2Hz,1H), 9.30(dd,J=5.4,1.3Hz,1 H), 8.42(dd,J=5.4,2.4Hz,1H), 8.27(s,1H), 8.21(d,J=8.5Hz,1H), 7.41(d,J=8.5Hz,1H).

[0340] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.42, 151.55, 149.87, 149.79, 133.23, 132.83, 131.78, 131.64, 129.77, 124.00, 120.57.

[0341] HRMS (APCI): Theoretical value (C 11 H7ClN3S)[M+H] + =248.0044, measured value [M+H] + =248.0045.

[0342] FTIR (NEET), CM -1 :3044, 3012, 2425, 2041, 1583, 1562, 1527, 1494, 1381, 1353, 1148, 1123, 828, 814, 723, 677, 648, 477.

[0343] (Preparation example 40: 5-(1-methyl-1H-pyrazole-4-yl)-3-(pyridazine-4-yl)thieno[3,2-b]-pyridine)

[0344] [ka]

[0345] The compounds were prepared according to general procedure B using 5-chloro-3-(pyridazin-4-yl)thieno[3,2-b]pyridine (Preparation Example 39) (50 mg, 0.202 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (53 mg, 0.252 mmol). After 24 hours, additional 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (53 mg, 0.252 mmol), tripotassium phosphate (129 mg, 0.606 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7 mg, 0.010 mmol), and H2O (0.5 mL) were added, and the mixture was refluxed for a further 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA / methanol, gradient 20:80:0 to 0:90:10). The product was obtained as a white solid (52 mg, 89% yield).

[0346] 1H NMR(500MHz,Methanol-d4)δ(ppm)10.07(s,1H), 9.24(d,J=5.5Hz,1H), 8.68(q,J=3.0Hz, 2H), 8.31(d,J=8.5Hz,1H), 8.24(s,1H), 8.09(s,1H), 7.64(d,J=8.5Hz,1H), 3.98(s,3H).

[0347] 13 C NMR(126MHz,Methanol-d4)δ(ppm)153.75, 152.65, 151.46, 151.26, 138.81, 13 5.24, 134.37, 133.10, 133.00, 131.26, 129.81, 126.01, 124.89, 117.47, 39.16.

[0348] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H] + =294.0808, measured value [M+H] + = 294.0809.

[0349] FTIR (NEET), CM -1 :3071, 1577, 1553, 1400, 1366, 1215, 1189, 1178, 1051, 998, 979, 857, 814, 676, 648, 488.

[0350] (Preparation Example 41: 4-(5-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-yl)morpholine (intermediate))

[0351] [ka]

[0352] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (300 mg, 1.21 mmol) and 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-yl)morpholine (438 mg, 1.51 mmol) according to general procedure A. Reaction temperature: 80°C. Reaction time: 3.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 90:10 to 60:40 gradient). The product was obtained as a white solid (250 mg, 62% yield).

[0353] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.76(d,J=1.7Hz,1H), 8.23(dd,J=8.9,2.5Hz,1H), 8.14(d,J=8.5Hz,1 H), 7.78(s,1H), 7.32(d,J=8.5Hz,1H), 6.77(d,J=8.8Hz,1H), 3.85(t,J=5.1Hz,4H), 3.59(t,J=5.0Hz,4H).

[0354] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 158.84, 153.04, 148.95, 147.22, 137.32, 133.72, 132.91, 132.67, 126.06, 120.06, 119.51, 106.43, 66.73, 45.60.

[0355] HRMS (APCI): Theoretical value (C 16 H 15 ClN3OS)[M+H] + =332.0619, measured value [M+H] + 332.0616.

[0356] FTIR (NEET), CM -1 :3061, 2958, 2867, 2850, 1606, 1562, 1530, 1516, 1484, 1444, 1372, 1323, 1244, 1141, 1112, 942, 794, 649, 595, 460.

[0357] (Preparation example 42: 4-(5-(5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)pyridine-2-yl)morpholine)

[0358] [ka]

[0359] The compound was prepared according to general procedure B using 4-(5-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)morpholine (Preparation Example 41) (45 mg, 0.136 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (35 mg, 0.170 mmol). Reaction temperature: 85°C. Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 80:20 to 40:60 gradient). The product was obtained as a white solid (36 mg, 70% yield).

[0360] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.94(br s,1H), 8.30(dd,J=8.8,2.3,1H), 8.15(d,J=8.4Hz,1H), 8.02(s,2H), 7.73(s,1H), 7.48(d,J= 8.4Hz,1H), 6.79(d,J=8.9Hz,1H), 3.98(s,3H), 3.88(t,J=4.7Hz,4H), 3.88(d,J=4.3Hz,4H).

[0361] 13 C NMR(126MHz,Chloroform-d)δ(ppm)158.74,153.23,149.49,147.43,137.77,137.50,133. 88,131.46,131.10,129.07,124.88,124.05,121.12,115.46,106.39,66.77,45.77,39.15.

[0362] HRMS (APCI): Theoretical value (C20 H 20 N5OS)[M+H] + =378.1383, measured value [M+H] + = 378.1386.

[0363] FTIR (NEET), CM -1 :2968, 2848, 1601, 1577, 1549, 1537, 1518, 1482, 1441, 1402, 1372, 1312, 1254, 1210, 1115, 980, 941, 820, 786, 638, 549, 468.

[0364] (Preparation example 43: 5-chloro-3-(1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[0365] [ka]

[0366] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (114 mg, 0.460 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (220 mg, 0.055 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (cyclohexane / siRNA, 90:10 to 70:30 gradient; then cyclohexane / siRNA, 100:0 to 80:20 gradient). The product was obtained as a pale yellow solid (96 mg, 48% yield).

[0367] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.56(d,J=5.0Hz,1H), 8.19(d,J=8.5Hz,1H), 8.11(d,J=8.3Hz,2H), 8.04(s,1H), 7.78 (d,J=4.0Hz,1H), 7.71(d,J=4.9Hz,1H), 7.36(d,J=8.5Hz,1H), 7.28(d,J=8.1Hz,2H), 6.73(d,J=4.0Hz,1H), 2.38(s,3H).

[0368] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.66, 149.56, 147.66, 145.24, 144.93, 135.35, 135.0 6, 133.11, 132.62, 131.86, 129.66, 128.17, 126.58, 121.43, 120.21, 119.08, 104.89, 21.62.

[0369] HRMS (APCI): Theoretical value (C 21 H 15 ClN3O2S2)[M+H] + =440.0289, measured value [M+H] + = 440.0291.

[0370] FTIR (NEET), CM -1 :1592, 1383, 1365, 1176, 1161, 1147, 811, 730, 681, 580.

[0371] (Preparation example 44: 5-(1-methyl-1H-pyrazole-4-yl)-3-(1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-yl)thieno[3,2-b]pyridine)

[0372] [ka]

[0373] The compound was prepared according to general procedure B using 5-chloro-3-(1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 43) (90 mg, 0.204 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (50 mg, 0.204 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30~40:60 gradient). The product was obtained as a pale yellow waxy substance (54 mg, yield 55%).

[0374] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.55(d,J=5.0Hz,1H), 8.20(d,J=8.5Hz,1H), 8.12(d,J=8.4Hz,2H), 7.97(s,1H), 7.95(s,1H), 7.87( s,1H), 7.77(d,J=1.7Hz,1H), 7.76(s,1H), 7.52(d,J=8.5Hz,1H), 7.29(d,J=8.1Hz,2H), 6.80(d,J=4.1Hz,1H), 3.95(s,3H), 2.38(s,3H).

[0375] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.84, 150.01, 148.00, 145.11, 144.82, 137.76, 136.04, 135.55, 133.61, 1 31.27, 131.24, 130.53, 129.62, 129.10, 128.11, 126.02, 123.77, 121.61, 119.27, 115.98, 105.81, 39.23, 21.63.

[0376] HRMS (APCI): Theoretical value (C 25 H 20 N5O2S2)[M+H] + =486.1053, measured value [M+H] + = 486.1056.

[0377] FTIR (NEET), CM-1 :2920, 2851, 1632, 1600, 1557, 1434, 1397, 1355, 1155, 1112, 828, 632.

[0378] (Preparation example 45: 5-(1-methyl-1H-pyrazole-4-yl)-3-(1H-pyrrolo[2,3-b]pyridine-4-yl)thieno[3,2-b]pyridine)

[0379] [ka]

[0380] 5-(1-methyl-1H-pyrazole-4-yl)-3-(1-tosyl-1H-pyrrolo[2,3-b]pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 44) (36 mg, 0.074 mmol) was dissolved in THF (2 mL) and methanol (2 mL)). 5M NaOH (0.7 mL) was added to the solution. Reaction temperature: 60 °C. Reaction time: 30 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:95:5 gradient). The product was obtained as a colorless waxy substance (14 mg, yield 58%).

[0381] 1 H NMR(500MHz,Chloroform-d)δ(ppm)10.03(s,1H), 8.47(d,J=5.1Hz,1H), 8.21(d,J=8.5Hz,1H), 8.14(s,1H), 8.01(s,1H) ), 7.95(s,1H), 7.87(d,J=5.0Hz,1H), 7.53(d,J=8.4Hz,1H), 7.41(d,J=3.6Hz,1H), 6.76(d,J=3.5Hz,1H), 3.95(s,3H).

[0382] 13C NMR(126MHz,Chloroform-d)δ(ppm)153.31, 149.82, 149.20, 142.66, 137.79, 135.28, 134.4 7, 131.36, 131.14, 130.28, 129.20, 124.86, 124.03, 119.04, 116.48, 115.76, 101.37, 39.18.

[0383] HRMS (APCI): Theoretical value (C 18 H 14 N5S)[M+H] + =332.0964, measured value [M+H] + =332.0965.

[0384] FTIR (NEET), CM -1 :3133, 1579, 1542, 1376, 1342, 1276, 985, 831, 797, 758, 657, 644.

[0385] (Preparation example 46: 5-chloro-3-(quinazolin-6-yl)thieno[3,2-b]pyridine (intermediate))

[0386] [ka]

[0387] To the degassed solution (6-bromoquinazoline (111 mg, 0.530 mmol) dissolved in dioxane (3.5 mL)), bis(pinacolate)diborone (134 mg, 0.530 mmol), tris(dibenzylideneacetone)dipalladium(0) (19 mg, 0.021 mmol), XPhos (32 mg, 0.070 mmol), and potassium acetate (166 mg, 1.70 mmol) were added, and the reaction mixture was refluxed for 6 hours. Subsequently, 3-bromo-5-chlorothieno[3,2-b]pyridine (100 mg, 0.424 mmol), tripotassium phosphate (88 mg, 0.417 mmol), and H2O (0.3 mL) were added, and the reaction mixture was stirred under reflux for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 30:70 gradient). The product was obtained as a pale yellow solid (29 mg, 23%).

[0388] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.52(s,1H), 9.35(s,1H), 8.75(d,J=1.9Hz,1H), 8.48(dd,J= 8.8,2.0Hz,1H), 8.21(d,J=8.5Hz,1H), 8.16(d,J=8.8Hz,1H), 8.08(s,1H), 7.39(d,J=8.5Hz,1H).

[0389] 13 C NMR(126MHz,Chloroform-d)δ(ppm)160.71, 155.42, 152.68, 149.66, 149.45, 13 4.61, 134.50, 133.34, 133.18, 132.92, 129.77, 128.66, 126.31, 125.31, 120.08.

[0390] HRMS (APCI): Theoretical value (C 15 H9ClN3S)[M+H] + =298.0199, measured value [M+H] + = 298.0199.

[0391] FTIR (NEET), CM-1 :3076, 1562, 1489, 1380, 1355, 1143, 124, 1076, 927, 841, 797, 780, 583, 550.

[0392] (Preparation example 47: 5-(1-methyl-1H-pyrazole-4-yl)-3-(quinazoline-6-yl)thieno[3,2-b]pyridine)

[0393] [ka]

[0394] The compound was prepared according to general procedure B using 5-chloro-3-(quinazolin-6-yl)thieno[3,2-b]pyridine (Preparation Example 46) (35 mg, 0.117 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (28 mg, 0.130 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 95:0:5 gradient). The product was obtained as a pale yellow solid (6 mg, 18% yield).

[0395] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.52(s,1H), 9.37(s,1H), 8.87(d,J=2.0Hz,1H), 8.61(dd,J=8.7,2.0Hz,1H) , 8.22(d,J=8.4Hz,1H), 8.17(s,1H), 8.06(s,1H), 8.03(s,1H), 7.99(s,1H), 7.55(d,J=8.5Hz,1H), 4.00(s,3H).

[0396] 13C NMR(126MHz,Chloroform-d)δ(ppm)160.50, 155.29, 152.92, 149.94, 149.58, 137.87, 134.99, 13 4.79, 134.40, 131.68, 131.38, 128.96, 128.56, 128.25, 126.26, 125.37, 123.95, 115.94, 39.30.

[0397] HRMS (APCI): Theoretical value (C 19 H 14 N5S)[M+H] + =344.0964, measured value [M+H] + =344.0965.

[0398] FTIR (NEET), CM -1 :1568, 1381, 1367, 1220, 1142, 995, 982, 833, 788, 648, 555, 489, 451.

[0399] (Preparation example 48: 5-chloro-3-(quinoxaline-6-yl)thieno[3,2-b]pyridine (intermediate))

[0400] [ka]

[0401] To a solution (6-bromoquinoxaline (157 mg, 0.753 mmol) dissolved in dioxane (3.5 mL)), bis(pinacolate)diborone (191 mg, 0.753 mmol), tris(dibenzylideneacetone)dipalladium(0) (28 mg, 0.030 mmol), XPhos (46 mg, 0.096 mmol), and potassium acetate (237 mg, 2.41 mmol) were added, and the reaction mixture was refluxed for 8 hours. Subsequently, 3-bromo-5-chlorothieno[3,2-b]pyridine (150 mg, 0.603 mmol), tripotassium phosphate (384 mg, 1.81 mmol), and H2O (0.4 mL) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 40:60 gradient). The product was obtained as a white solid (79 mg, 44%).

[0402] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.88(dd,J=16.8,1.8Hz,2H), 8.78(d,J=2.0Hz,1H),8. 45(dd,J=8.8,2.0Hz,1H), 8.21(dd,J=12.9,8.6Hz,2H), 8.11(s,1H), 7.38(d,J=8.5Hz,1H).

[0403] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.78, 149.46, 145.35, 144.94, 143.26, 14 2.74, 135.61, 135.05, 133.09, 132.91, 130.65, 130.02, 129.62, 128.49, 120.02.

[0404] HRMS (APCI): Theoretical value (C 15 H9ClN3S)[M+H] + =298.0199, measured value [M+H] + = 298.0202.

[0405] FTIR (NEET), CM -1:1635, 1564, 1382, 1153, 1123, 1028, 951, 902, 844, 832, 788, 734, 408.

[0406] (Preparation example 49: 5-(1-methyl-1H-pyrazole-4-yl)-3-(quinoxaline-6-yl)thieno[3,2-b]pyridine)

[0407] [ka]

[0408] The compound was prepared according to general procedure B using 5-chloro-3-(quinoxaline-6-yl)thieno[3,2-b]pyridine (Preparation Example 48) (40 mg, 0.134 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (32 mg, 0.154 mmol). Reaction time: 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 95:0:5 gradient). The product was obtained as a white solid (22 mg, 48% yield).

[0409] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.95~8.83 (m, 3H), 8.56 (dd, J=8.8, 2.0Hz, 1H), 8.22 (dd ,J=8.6,6.6Hz,2H), 8.06(s,1H), 8.05(d,J=4.1Hz,2H), 7.55(d,J=8.4Hz,1H), 3.99(s,3H).

[0410] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.01, 149.97, 145.25, 144.72, 143.37, 142.64, 137.84, 13 6.54, 135.17, 131.65, 131.29, 131.04, 129.22, 129.18, 128.84, 128.51, 123.94, 115.83, 39.26.

[0411] HRMS (APCI): Theoretical value (C 19 H 14 N5S)[M+H] + =344.0964, measured value [M+H] + =344.0962.

[0412] FTIR (NEET), CM -1 :3443, 3091, 2939, 1614, 1578, 1541, 1400, 1372, 1216, 1159, 1026, 864, 784.

[0413] (Preparation example 50: 5-chloro-3-(2H-indazole-5-yl)thieno[3,2-b]pyridine (intermediate))

[0414] [ka]

[0415] The compound was prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.805 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (216 mg, 0.885 mmol). Reaction time: 4.5 hours. The solvent was evaporated, and the residue was purified by two flash chromatography cycles (cyclohexane / siRNA, 100:0 to 40:60 gradient). The product was obtained as a white solid (146 mg, 63% yield).

[0416] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.49(s,1H), 8.38(d,J=8.5Hz,1H), 8.17(s,1H), 8 .14(s,1H), 7.99(dd,J=8.7,1.5Hz,1H), 7.64(d,J=8.7Hz,1H), 7.41(d,J=8.4Hz,1H).

[0417] 13C NMR(126MHz,Methanol-d4)δ(ppm)154.32, 150.03, 141.16, 137.48, 135.60, 134.97, 134.64, 129.87, 128.90, 128.29, 124.59, 121.60, 120.52, 111.04.

[0418] HRMS (APCI): Theoretical value (C 14 H9N3ClS)[M+H] + =286.0200, measured value [M+H] + = 286.0202.

[0419] FTIR (NEET), CM -1 :3503~2632, 1541, 1381, 1125, 949, 786.

[0420] (Preparation Example 51: 3-(2H-indazole-5-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0421] [ka]

[0422] The compound was prepared according to general procedure B using 5-chloro-3-(2H-indazole-5-yl)thieno[3,2-b]pyridine (Preparation Example 50) (45 mg, 0.157 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (39 mg, 0.550 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 0:100 gradient). The product was obtained as a white solid (42 mg, 81% yield).

[0423] 1H NMR(500MHz,Methanol-d4)δ(ppm)8.60(dd,J=1.6,0.9Hz,1H), 8.31(d,J=8.5Hz,1H), 8.20(s,1H), 8.16(d,J=1 .1Hz,1H), 8.11(dd,J=8.8,1.6Hz,1H), 8.09(d,J=0.9Hz,1H), 8.06(s,1H), 7.65(t,J=8.8Hz,2H), 3.96(s,3H).

[0424] 13 C NMR(126MHz,Methanol-d4)δ(ppm)154.48, 150.76, 138.80, 137.87, 135.54, 133.36, 13 2.75, 131.04, 129.25, 129.22, 128.15, 125.42, 124.64, 121.61, 116.79, 110.92, 39.12.

[0425] HRMS (APCI): Theoretical value (C 18 H 14 N5S)[M+H] + =332.0964, measured value [M+H] + =332.0965.

[0426] FTIR (NEET), CM -1 :1579, 1544, 1224, 1213, 908, 824, 778, 770, 701, 451, 428.

[0427] (Preparation example 52: 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (intermediate))

[0428] [ka]

[0429] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (109 mg, 0.438 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (129 mg, 0.526 mmol). Reaction time: 75 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 0:100 gradient). The product was obtained as a white solid (75 mg, 60% yield).

[0430] 1 H NMR (500MHz, Chloroform-d) δ(ppm)9.71(s,1H), 8.42(s,1H), 8.20(d,J=8.5Hz,1H), 8.04(d,J=10.5Hz,2H), 7.88(d,J=9.5Hz,1H), 7.40(d,J=8.5Hz,1H).

[0431] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 154.09, 152.20, 149.55, 133.22, 132.82, 130.88, 130.35, 129.12, 127.79, 121.17, 120.30, 116.33.

[0432] HRMS (APCI): Theoretical value (C 13 H8ClN4S)[M+H] + =287.0153, measured value [M+H] + = 287.0153.

[0433] FTIR (NEET), CM -1 :3058,1637,1539,1499,1381,1315,1255,1187,1150,1121,910,832,805,729,655,578,422.

[0434] (Preparation Example 53: 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0435] [ka]

[0436] The compound was prepared according to general procedure B using 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (Preparation Example 52) (65 mg, 0.227 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (57 mg, 0.272 mmol). Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 100:0 to 90:10 gradient). The product was obtained as a white solid (62 mg, 83% yield).

[0437] 1 H NMR(500MHz,DMSO-d6)δ(ppm)10.11(s,1H), 8.69(s,1H), 8.57(s,1H), 8.56(d,J=8.4Hz,1H), 8.45(dd, J=9.4,1.8Hz,1H), 8.38(s,1H), 8.13(s,1H), 8.00(d,J=9.3Hz,1H), 7.78(d,J=8.5Hz,1H), 3.95(s,3H).

[0438] 13 C NMR(126MHz,DMSO-d6)δ(ppm)154.32, 151.98, 149.61, 148.99, 137.26, 132.38, 131. 01, 130.46, 129.92, 129.67, 129.38, 126.87, 122.79, 121.50, 116.10, 115.77, 38.81.

[0439] HRMS (APCI): Theoretical value (C 17 H 13 N6S)[M+H] + =333.0917, measured value [M+H] + = 333.0920.

[0440] FTIR (NEET), CM -1 :2924,1590,1578,1436,1190,1165,1118,1100,1028,833,750,723,699,565,531,492.

[0441] (Preparation example 54: 5-chloro-3-(pyrazolo[1,5-a]pyrimidine-6-yl)thieno[3,2-b]pyridine (intermediate))

[0442] [ka]

[0443] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (80 mg, 0.322 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine (95 mg, 0.386 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient). The product was obtained as a pale yellow solid (39 mg, 42% yield).

[0444] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.82(d,J=2.6Hz,1H), 8.95(d,J=2.3Hz,1H ), 8.22~8.17(m,2H), 8.07(s,1H), 7.40(d,J=8.4Hz,1H), 6.76(d,J=1.8Hz,1H).

[0445] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.31, 149.61, 149.07, 147.56, 145.68, 133.81, 133.19, 132.63, 128.91, 128.33, 120.39, 115.15, 97.11.

[0446] HRMS (APCI): Theoretical value (C13 H8ClN4S)[M+H] + =287.0153, measured value [M+H] + = 287.0152.

[0447] (Preparation example 55: 5-(1-methyl-1H-pyrazole-4-yl)-3-(pyrazolo[1,5-a]pyrimidine-6-yl)thieno[3,2-b]pyridine)

[0448] [ka]

[0449] The compound was prepared according to general procedure B using 5-chloro-3-(pyrazolo[1,5-a]pyrimidine-6-yl)thieno[3,2-b]pyridine (Preparation Example 54) (50 mg, 0.174 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (40 mg, 0.191 mmol). Reaction time: 5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane:siRNA, 60:40 to 0:100 gradient) and preparation TLC (toluene / methanol, 95:5, 5 elutions). The product was obtained as a white solid (5 mg, 9% yield).

[0450] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.88(d,J=1.2Hz,1H), 9.07(d,J=2.1Hz,1H), 8.21(d,J=8.5Hz,1H), 8.19(d, J=2.4Hz,1H), 8.07(s,1H), 8.03(s,1H), 8.00(s,1H), 7.56(d,J=8.4Hz,1H), 6.76(d,J=1.5Hz,1H), 4.00(s,3H).

[0451] 13C NMR(126MHz,Chloroform-d)δ(ppm)152.52, 150.13, 149.62, 145.42, 137.74, 133.5 7, 131.43, 131.35, 129.25, 129.00, 127.11, 123.50, 116.18, 116.10, 96.96, 39.32.

[0452] HRMS (APCI): Theoretical value (C 17 H 13 N6S)[M+H] + =333.0917, measured value [M+H] + =333.0915.

[0453] FTIR (NEET), CM -1 :3422, 3084, 2925, 1619, 1580, 1556, 1444, 1220, 980, 809, 723.

[0454] (Preparation example 56: 5-chloro-3-(imidazo[1,2-a]pyridine-6-yl)thieno[3,2-b]pyridine (intermediate))

[0455] [ka]

[0456] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (80 mg, 0.322 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine (94 mg, 0.386 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient). The product was obtained as a brown solid (41 mg, 45% yield).

[0457] 1H NMR(500MHz,Chloroform-d)δ(ppm)9.46(s,1H), 8.19(d,J=8.5Hz,1H), 8.01(s,1 H), 7.82(d,J=9.5Hz,1H), 7.76(s,2H), 7.72~7.66(m,1H), 7.39(d,J=8.5Hz,1H).

[0458] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.30, 149.21, 143.68, 133.26, 132.92, 132.26, 131.30, 128.61, 126.08, 125.37, 120.05, 119.85, 117.10, 113.63.

[0459] HRMS (APCI): Theoretical value (C 14 H9ClN3S)[M+H] + =286.0200, measured value [M+H] + = 286.0200.

[0460] FTIR (NEET), CM -1 :2917, 2850, 1694, 1563, 1522, 1366, 1146, 1127, 837, 803.

[0461] (Preparation Example 57: 3-(imidazo[1,2-a]pyridine-6-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0462] [ka]

[0463] The compound was prepared according to general procedure B using 5-chloro-3-(imidazo[1,2-a]pyridine-6-yl)thieno[3,2-b]pyridine (Preparation Example 56) (50 mg, 0.175 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (40 mg, 0.192 mmol). Reaction time: 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (Âxy / methanol, 100:0 to 95:5 gradient) and preparation TLC (toluene:methanol, 95:5, 5 elutions). The product was obtained as a white solid (15 mg, 26% yield).

[0464] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.50(s,1H), 8.18(d,J=8.4Hz,1H), 8.07(s,1H), 7. 96(s,1H), 7.89(d,J=1.6Hz,1H), 7.76~7.66(m,4H), 7.52(d,J=8.5Hz,1H), 4.00(s,3H).

[0465] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.75, 149.68, 144.67, 137.89, 133.82, 132.04, 131.6 7, 131.39, 128.84, 126.86, 125.53, 125.29, 123.94, 120.08, 117.34, 115.91, 113.10, 39.29.

[0466] HRMS (APCI): Theoretical value (C 18 H 14 N5S)[M+H] + =332.0964, measured value [M+H] + =332.0961.

[0467] FTIR (NEET), CM -1 :3396, 3088, 2925, 1579, 1549, 1400, 1312, 1217, 1143, 857.

[0468] (Preparation example 58: 3-([1,2,4]triazolo[4,3-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (intermediate))

[0469] [ka]

[0470] The compounds were prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (150 mg, 0.603 mmol) and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[4,3-a]pyridine (177 mg, 0.724 mmol). Reaction time: 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 70:30 gradient). The product was obtained as a brown solid (107 mg, 62% yield).

[0471] 1 H NMR(500MHz,Methanol-d4)δ(ppm)9.59(s,1H), 9.33(s,1H), 8.50(s,1H), 8.45(d, J=8.5Hz,1H), 8.06(d,J=9.4Hz,1H), 7.85(d,J=9.6Hz,1H), 7.50(d,J=8.5Hz,1H).

[0472] 13 C NMR(126MHz,Methanol-d4)δ(ppm)153.50,150.37,149.72,138.60,135.33,134.67,132.44,131.43,131.03,124.26,122.79,121.19,115.60.

[0473] HRMS (APCI): Theoretical value (C 13 H8ClN4S)[M+H] + =287.0153, measured value [M+H] + = 287.0154.

[0474] FTIR (NEET), CM-1 :3402, 3064, 2005, 1584, 1564, 1529, 1487, 1437, 1146, 1127, 799.

[0475] (Preparation example 59: 3-([1,2,4]triazolo[4,3-a]pyridine-6-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0476] [ka]

[0477] The compound was prepared according to general procedure B using 3-([1,2,4]triazolo[4,3-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (Preparation Example 58) (40 mg, 0.139 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (34 mg, 0.167 mmol). Reaction time: 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:95:5 gradient) and preparation TLC (siRNA / methanol, 95:5). The product was obtained as a white solid (10 mg, 22% yield).

[0478] 1 H NMR(500MHz,DMSO-d6)δ(ppm)9.90(s,1H), 9.57(s,1H), 8.64(s,1H), 8.55(d,J=8.5Hz,1H), 8.49(s,1H) ), 8.24(s,1H), 8.06(dd,J=9.6,1.6Hz,1H), 7.92(d,J=9.6Hz,1H), 7.79(d,J=8.5Hz,1H), 3.96(s,3H).

[0479] 13C NMR(126MHz,DMSO-d6)δ(ppm)151.99, 149.76, 147.60, 137.70, 137.67, 132.37, 130. 97, 130.11, 129.82, 129.48, 128.68, 122.66, 122.63, 120.39, 116.07, 114.86, 38.80.

[0480] HRMS (APCI): Theoretical value (C 17 H 13 N6S)[M+H] + =333.0917, measured value [M+H] + =333.0914.

[0481] FTIR (NEET), CM -1 :1576, 1549, 1402, 1220, 994, 874, 771, 655, 492.

[0482] (Preparation example 60: 5-chloro-3-(pyrazolo[1,5-a]pyrimidine-2-yl)thieno[3,2-b]pyridine (intermediate))

[0483] [ka]

[0484] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (50 mg, 0.021 mmol) dissolved in dioxane (1 mL), potassium carbonate (87 mg, 0.063 mmol), SPhosPdG3 (16 mg, 0.002 mmol), SPhos (4 mg, 0.011 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine (59 mg, 0.024 mmol), and H2O (0.3 mL) were added, and the reaction mixture was refluxed for 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 40:60 gradient). The product was obtained as a white solid (42 mg, 72%).

[0485] 1 H NMR(500MHz,Chloroform-d)δ9.54(s,1H), 8.80~8.76(m,2H), 8.60(dd,J=4.0,1.7 Hz,1H), 8.15(d,J=8.4Hz,1H), 7.33(d,J=8.4Hz,1H), 6.90(dd,J=7.0,4.0Hz,1H).

[0486] 13 C NMR (126MHz, Chloroform-d) δ153.54, 149.28, 148.78, 145.65, 143.97, 135.39, 132.80, 131.92, 126.78, 126.58, 119.30, 108.18, 104.67.

[0487] HRMS (APCI): Theoretical value (C 13 H8ClN4S)[M+H] + =287.0153, measured value [M+H] + = 287.0150.

[0488] FTIR (NEET), CM -1 :1614, 1561, 1520, 1387, 1297, 1144, 1121, 839, 778, 752, 716, 578, 453.

[0489] (Preparation example 61: 5-(1-methyl-1H-pyrazole-4-yl)-3-(pyrazolo[1,5-a]pyrimidine-2-yl)thieno[3,2-b]pyridine)

[0490] [ka]

[0491] The compound was prepared according to general procedure B using 5-chloro-3-(pyrazolo[1,5-a]pyrimidine-2-yl)thieno[3,2-b]pyridine (Preparation Example 60) (42 mg, 0.146 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (37 mg, 0.176 mmol). Reaction time: 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 20:80 to 0:100 gradient). The product was obtained as a white solid (15 mg, 31% yield).

[0492] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.72(s,1H), 8.77(dd,J=6.9,1.8Hz,1H), 8.72(s,1H), 8.61(dd,J=4.1,1.7Hz, 1H), 8.18(d,J=8.4Hz,1H), 8.10(d,J=7.8Hz,2H), 7.51(d,J=8.4Hz,1H), 6.90(dd,J=7.0,4.0Hz,1H), 4.02(s,3H).

[0493] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.89, 149.37, 149.12, 145.69, 144.20, 137.78, 13 5.30, 131.05, 130.78, 129.05, 126.92, 125.44, 124.28, 115.34, 108.10, 105.55, 39.25.

[0494] HRMS (APCI): Theoretical value (C 17 H 13 N6S)[M+H] + =333.0917, measured value [M+H] + =333.0919.

[0495] FTIR (NEET), CM -1 :2924, 2854, 1733, 1523, 1436, 1419, 1271, 1262, 1066, 971, 842, 801, 652, 599.

[0496] (Preparation Example 62: 5-chloro-3-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (intermediate))

[0497] [ka]

[0498] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (205 mg, 0.825 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (206 mg, 0.990 mmol) according to general procedure A. Reaction time: 48 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 70:30 gradient). The product was obtained as a white solid (30 mg, 15% yield).

[0499] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.44(s,1H), 8.11(d,J=8.4Hz,1H), 7.98(s,1H), 7.75(s,1H), 7.31(d,J=8.4Hz,1H), 4.01(s,3H).

[0500] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.87, 148.88, 137.31, 132.88, 132.38, 128.76, 128.56, 124.01, 119.47, 115.25, 39.13.

[0501] HRMS theoretical value (C 11 H9ClN3S)[M+H] + 250.020, measured value [M+H] + = 250.0202.

[0502] FTIR (NEET), CM -1:2922, 2851, 1560, 1531, 1382, 1142, 1123, 981, 839, 795, 719.

[0503] (Preparation Example 63: 3,5-bis(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0504] [ka]

[0505] The compounds were prepared according to general procedure B using 5-chloro-3-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 62) (26 mg, 0.104 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (26 mg, 0.125 mmol). Reaction temperature: 95°C. Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient). The product was obtained as a white solid (13 mg, 45% yield).

[0506] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.39 (s, 1H), 8.15 (s, 1H), 8.13 (d, J = 8.4Hz, 1H), 8 .07(s,1H), 7.99(s,1H), 7.68(s,1H), 7.47(d,J=8.4Hz,1H), 4.03(s,3H), 4.01(s,3H).

[0507] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.18, 149.42, 137.91, 137.78, 131.23, 1 31.06, 128.83, 128.76, 128.50, 124.23, 122.85, 116.22, 115.62, 39.26, 39.15.

[0508] HRMS theoretical value (C 15 H14 N5S)[M+H] + 296.0964, measured value [M+H] + =296.0967.

[0509] FTIR (NEET), CM -1 :3098, 2936, 1578, 1541, 1406, 1370, 1217, 1184, 1168, 1057, 980, 866, 833, 807, 778, 702, 645, 612, 593.

[0510] (Preparation example 64: 3-(1-benzyl-1H-pyrazole-4-yl)-5-chlorothieno[3,2-b]pyridine (intermediate))

[0511] [ka]

[0512] The compound was prepared according to general procedure A using 3-bromo-5-chlorothieno[3,2-b]pyridine (Preparation Example 64) (200 mg, 0.804 mmol) and 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (251 mg, 0.884 mmol). Reaction temperature: 80°C. Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 50:50 gradient). The product was obtained as a white solid (111 mg, 42% yield).

[0513] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.53(s,1H), 8.30(d,J=8.5Hz,1H), 8.21(s,1H), 8 .08(s,1H), 7.39~7.34(m,3H), 7.31(t,J=3.2Hz,2H), 7.30~7.28(m,1H), 5.42(s,2H).

[0514] 13C NMR(126MHz,Methanol-d4)δ(ppm)153.99, 149.95, 138.85, 138.22, 134.70, 133.99, 129.80, 129.03, 129.00, 128.65, 126.64, 120.46, 117.16, 56.68.

[0515] HRMS theoretical value (C 17 H 13 ClN3S)[M+H] + 326.0513, measured value [M+H] + = 326.0514.

[0516] FTIR (NEET), CM -1 :3042, 1529, 1438, 1163, 1055, 832, 762, 719, 703, 474.

[0517] (Preparation example 65: 3-(1-benzyl-1H-pyrazole-4-yl)-5-chlorothieno[3,2-b]pyridine)

[0518] [ka]

[0519] Following general procedure B, the compound was prepared using 5-chloro-3-phenylthieno[3,2-b]pyridine (Preparation Example 64) (43 mg, 0.132 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (35 mg, 0.168 mmol), and triethylamine (0.1 mL, 0.396 mmol) instead of potassium phosphate. After 2 hours, an additional triethylamine (0.2 mL, 0.343 mmol) was added, and the mixture was refluxed for a further 6 hours. The solvent was evaporated, and the residue was purified by preparation TLC (hexane / siRNA, 25:75). The product was obtained as a white solid (13 mg, 26% yield).

[0520] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.40(s,1H), 8.21(s,1H), 8.11(d,J=8.4Hz,1H), 7.97(s,1H), 7.84(s,1 H), 7.68(s,1H), 7.45(d,J=8.4Hz,1H), 7.43~7.38(m,2H), 7.36(t,J=6.1Hz,3H), 5.43(s,2H), 3.98(s,3H).

[0521] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.12, 149.36, 137.94, 137.81, 136.41, 131.16, 131.02, 1 28.91, 128.76, 128.65, 128.19, 128.08, 127.77, 124.14, 122.87, 116.43, 115.50, 56.32, 39.23.

[0522] HRMS theoretical value (C 21 H 18 N5S)[M+H] + =372.1277, measured value [M+H] + = 372.1277.

[0523] FTIR (NEET), CM -1 :3147, 2922, 2852, 1574, 1374, 1179, 1052, 980, 850, 782, 709, 615, 576.

[0524] (Preparation example 66: 5-chloro-3-(isothiazol-5-yl)thieno[3,2-b]pyridine (intermediate))

[0525] [ka]

[0526] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (400 mg, 1.61 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isothiazole (408 mg, 1.93 mmol) according to general procedure A. Reaction time: 5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 90:10 to 80:20 gradient). The product was obtained as a white solid (246 mg, 40% yield).

[0527] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.53(d,J=1.8Hz,1H), 8.16(d,J=8.4Hz,1H), 8.11(s,1H), 7.84(d,J=1.8Hz,1H), 7.38(d,J=8.5Hz,1H).

[0528] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 156.99, 156.58, 151.79, 149.66, 133.07, 131.99, 128.38, 127.57, 120.44, 120.42.

[0529] HRMS (APCI): Theoretical value (C 10 H6ClN2S2)[M+H] + =252.9655, measured value [M+H] + = 252.9656.

[0530] FTIR (NEET), CM -1 :3086, 3052, 1561, 1543, 1410, 1390, 1327, 1161, 1125, 838, 796, 757.

[0531] (Preparation Example 67: 3-(isothiazol-5-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0532] [ka]

[0533] The compound was prepared according to general procedure B using 5-chloro-3-(isothiazol-5-yl)thieno[3,2-b]pyridine (Preparation Example 66) (45 mg, 0.178 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (44 mg, 0.214 mmol). Reaction time: 45 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 50:50 gradient). The product was obtained as a white solid (32 mg, 70% yield).

[0534] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.52(d,J=1.8Hz,1H), 8.18(s,1H), 8.14(d,J=8.5Hz, 1H), 8.08(s,1H), 8.07(s,1H), 7.73(d,J=1.8Hz,1H), 7.53(d,J=8.5Hz,1H), 4.03(s,3H).

[0535] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 157.44, 155.77, 151.96, 150.09, 137.83, 131.26, 130.29, 129.75, 128.03, 126.53, 123.49, 119.35, 116.04, 39.33.

[0536] HRMS (APCI): Theoretical value (C 14 H 11 N4S2)[M+H] + =299.0420, measured value [M+H] + =299.0424.

[0537] FTIR (NEET), CM -1 :1608, 1546, 1400, 1255, 1167, 993, 828, 808, 784, 746, 649, 551, 490, 432.

[0538] (Preparation example 68: 5-chloro-3-(thiazole-5-yl)thieno[3,2-b]pyridine (intermediate))

[0539] [ka]

[0540] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (250 mg, 1.01 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazole (256 mg, 1.21 mmol) according to general procedure A. Reaction time: 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 70:30 to 30:70 gradient). The product was obtained as a white solid (47 mg, 19% yield).

[0541] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.85 (s, 1H), 8.66 (s, 1H), 8.15 (d, J = 8.4 Hz, 1 H), 7.97 (s, 1 H), 7.37 (d, J = 8.4 Hz, 1 H).

[0542] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.75, 151.91, 149.45, 141.13, 133.03, 132.25, 129.96, 127.66, 127.32, 120.26.

[0543] HRMS (APCI): Theoretical value (C 10 H6ClN2S2)[M+H] + =252.9655, measured value [M+H] + = 252.9657.

[0544] FTIR (NEET), CM -1 :3071, 1561, 1526, 1387, 1149, 1124, 1107, 871, 845, 786, 762, 708, 600, 471.

[0545] (Preparation example 69: 5-(1-methyl-1H-pyrazole-4-yl)-3-(thiazole-5-yl)thieno[3,2-b]pyridine)

[0546] [ka]

[0547] The compound was prepared according to general procedure B using 5-chloro-3-(thiazole-5-yl)thieno[3,2-b]pyridine (Preparation Example 68) (40 mg, 0.158 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (39 mg (0.189 mmol)). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 40:60 to 0:100 gradient). The product was obtained as a brown solid (29 mg, 62% yield).

[0548] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.86(s,1H), 8.70(s,1H), 8.15(d,J=8.5Hz,1H), 8.09(d,J=4.0Hz,2H), 7.94(s,1H), 7.52(d,J=8.5Hz,1H), 4.01(s,3H).

[0549] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.58, 151.98, 149.87, 140.55, 137.87, 131.22, 130.85, 130.68, 129.31, 127.40, 126.13, 123.76, 115.97, 39.27.

[0550] HRMS (APCI): Theoretical value (C 14 H 11 N4S2)[M+H] + =299.0420, measured value [M+H] + =299.0421.

[0551] FTIR (NEET), CM -1 :3080, 1579, 1404, 1215, 990, 872, 836, 813, 605.

[0552] (Preparation example 70: 5-chloro-3-(3-methyl-1,2,4-thiadiazole-5-yl)thieno[3,2-b]pyridine (intermediate))

[0553] [ka]

[0554] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (100 mg, 0.402 mmol) dissolved in dioxane (4 mL)), 3-methyl-5-(tributylstanyl)-1,2,4-thiadiazole (157 μL, 0.482 mmol) was added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 70:30 gradient). The product was obtained as a white solid (37 mg, 34% yield).

[0555] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.74 (s, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 2.76 (s, 3H).

[0556] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 177.45, 171.89, 151.86, 149.90, 133.24, 132.41, 132.00, 127.79, 120.70, 18.74.

[0557] HRMS (APCI): Theoretical value (C 10 H7ClN3S2)[M+H] + =267.9764, measured value [M+H] + = 267.9766.

[0558] FTIR (NEET), CM -1 :2977, 1714, 1609, 1578, 1565, 1381, 1263, 1164, 1124, 845, 790, 737, 659.

[0559] (Preparation Example 71: 3-(3-methyl-1,2,4-thiadiazole-5-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0560] [ka]

[0561] The compounds were prepared according to general procedure B using 5-chloro-3-(3-methyl-1,2,4-thiadiazole-5-yl)thieno[3,2-b]pyridine (Preparation Example 70) (40 mg, 0.149 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (37 mg, 0.178 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient). The product was obtained as a brown solid (20 mg, 44% yield).

[0562] 1 H NMR(500MHz,DMSO-d6)δ(ppm)9.00(s,1H), 8.60(d,J=8.4Hz,1H), 8.51(s,1H), 8.22(s,1H), 7.85(d,J=8.5Hz,1H), 3.97(s,3H), 2.68(s,3H).

[0563] 13 C NMR (126MHz, DMSO-d6) δ (ppm) 177.36, 171.12, 151.14, 150.15, 137.65, 133.55, 132.83, 130.22, 126.35, 122.16, 116.65, 38.83, 18.49.

[0564] HRMS (APCI): Theoretical value (C 14 H 12 N5S2)[M+H] + =314.0529, measured value [M+H] + =314.0527.

[0565] FTIR (NEET), CM -1 :1581, 1546, 1366, 1290, 982, 819, 806, 694.

[0566] (Preparation Example 72: (5-chlorothieno[3,2-b]pyridine-3-yl)(phenyl)methanone (intermediate))

[0567] [ka]

[0568] To a solution (dissolved in hexamethylphosphoramide (8 mL) with 3-bromo-5-chlorothieno[3,2-b]pyridine (500 mg, 2.01 mmol)), tributyl(phenyl)stanane (659 μL, 2.01 mmol) and bis(triphenylphosphine)palladium(II) dichloride (113 mg, 0.161 mmol) were added, and the reaction mixture was stirred in the presence of carbon monoxide at 10 atm and 75°C for 60 hours. The reaction mixture was quenched with water (15 mL) and extracted with toluene (2 × 15 mL). The integrated organic extract was washed with water (2 × 15 mL) and saline (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. After evaporation of the solvent, the residue was purified by flash chromatography (cyclohexane / toluene, 98:2 to 80:20 gradient). The product was obtained as a yellow, waxy substance (95 mg, 17%).

[0569] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.21(s,1H), 8.17(d,J=8.5Hz,1H), 7.91(dd,J =8.2,1.1Hz,2H), 7.63~7.58(m,1H), 7.48(t,J=7.8Hz,2H), 7.36(d,J=8.5Hz,1H).

[0570] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 189.59, 152.99, 150.18, 137.69, 137.66, 135.75, 133.27, 132.72, 132.16, 130.17, 128.35, 120.55.

[0571] HRMS (APCI): Theoretical value (C 14 H9ClNOS)[M+H] + =274.0088, measured value [M+H] + =274.0088.

[0572] FTIR (NEET), CM -1 :3093, 3065, 1655, 1563, 1385, 1323, 1237, 1148, 1125, 846, 724, 696, 671.

[0573] (Preparation Example 73: (5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)(phenyl)-methanone)

[0574] [ka]

[0575] The compound was prepared according to general procedure B using (5-chlorothieno[3,2-b]pyridine-3-yl)(phenyl)methanone (Preparation Example 72) (30 mg, 0.109 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (27 mg, 0.131 mmol). Reaction temperature: 110°C. Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 50:50 gradient). The product was obtained as a pale yellow waxy substance (27 mg, 77%).

[0576] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.29(s,1H), 8.17(d,J=8.4Hz,1H), 7.92(dd,J=8.3,1.1 Hz,2H), 7.81(s,1H), 7.73(s,1H), 7.61(t,J=7.4Hz,1H), 7.48(t,J=7.7Hz,3H), 3.89(s,3H).

[0577] 13 C NMR(126MHz,Chloroform-d)δ(ppm)190.69, 153.02, 150.31, 138.53, 137.75, 137.7 1, 136.17, 132.67, 131.06, 130.92, 130.23, 129.54, 128.04, 123.56, 116.02, 39.12.

[0578] HRMS (APCI): Theoretical value (C 18 H 14 N3OS)[M+H] + =320.0852, measured value [M+H] + =320.0853.

[0579] FTIR (NEET), CM -1 :1652, 1578, 1538, 1400, 1214, 1177, 985, 839, 726, 694, 661.

[0580] (Preparation Example 74: (5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)(phenyl)methanone)

[0581] [ka]

[0582] To the solution (in which (5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-yl)(phenyl)methanone (18 mg, 0.056 mmol) (Preparation Example 73) was dissolved in methanol (1.5 mL)), sodium tetrahydridoborate (3 mg, 1.3 mmol) was added, and the reaction mixture was stirred at 25°C for 30 minutes. An additional 3 mg, 1.3 mmol of sodium tetrahydridoborate was added, and the reaction mixture was heated at 30°C for 2 hours, followed by stirring at 25°C for 16 hours. Complete conversion was confirmed by NMR analysis of the crude mixture. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 20:80 to 0:100 gradient). The product was obtained as a white solid (13 mg, 72%).

[0583] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.13(d,J=8.5Hz,1H), 8.02(s,1H), 8.00(s,1H), 7.56(d,J=7.4Hz,2H), 7.48( d,J=8.5Hz,1H), 7.40(t,J=7.6Hz,2H), 7.32(t,J=7.3Hz,1H), 7.13(s,1H), 6.28(s,1H), 6.13(s,1H), 3.99(s,3H).

[0584] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 148.67, 142.31, 138.71, 137.78, 131.72, 131.63, 129.05, 128.44, 127.74, 127.17, 126.86, 115.82, 72.96, 39.27.

[0585] HRMS (APCI): Theoretical value (C 18 H 16 N3OS)[M+H] + 322.1009, measured value [M+H] + = 322.1008.

[0586] FTIR (NEET), CM -1 :3550~3087, 2923, 2853, 1717, 1654, 1580, 1493, 1454, 1215, 982, 824, 700.

[0587] (Preparation Example 75: 5-Chloro-N-phenylthieno[3,2-b]pyridine-3-amine (intermediate))

[0588] [ka]

[0589] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.804 mmol) dissolved in toluene (4 mL)), aniline (87 μL, 0.960 mmol), tert-butoxide sodium (85 mg, 0.884 mmol), and bis(tri-tert-butylphosphine)palladium(0) (21 mg, 0.040 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10). The product was obtained as a pale yellow solid (149 mg, 71%).

[0590] 1 H NMR (500MHz, Chloroform-d) δ8.07(d,J=8.4Hz,1H), 7.38~7.31(m,3H), 7.29~7.26(m,2H), 7.07(br s,1H), 7.00~6.95(m,1H).

[0591] 13C NMR (126MHz, Chloroform-d) δ148.11, 148.04, 142.26, 134.36, 133.17, 130.57, 129.47, 121.20, 120.25, 117.06, 102.12.

[0592] HRMS (APCI): Theoretical value (C 13 H 10 ClN2S)[M+H] + =261.0248, measured value [M+H] + = 261.0251.

[0593] FTIR (NEET), CM -1 :3381, 1593, 1570, 1532, 1391, 1156, 1119, 750, 738, 692.

[0594] (Preparation Example 76: 5-(1-methyl-1H-pyrazole-4-yl)-N-phenylthieno[3,2-b]pyridine-3-amine)

[0595] [ka]

[0596] The compound was prepared according to general procedure B using 5-chloro-N-phenylthieno[3,2-b]pyridine-3-amine (Preparation Example 75) (50 mg, 0.191 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (48 mg, 0.229 mmol). Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 40:60 gradient). The product was obtained as a pale yellow solid (44 mg, 76%).

[0597] 1H NMR(500MHz,Chloroform-d)δ8.10(d,J=8.3Hz,1H), 8.06(s,2H), 7.50(d,J=8.4Hz,1H), 7.39~7.34(m,2H), 7.33~7.29(m,2H), 7.01(br s,1H), 6.99~6.95(m,1H), 4.01(s,3H).

[0598] 13 C NMR (126MHz, Chloroform-d) δ148.51, 142.62, 137.86, 136.62, 134.48, 131.40, 129.44, 128.97, 120.83, 116.89, 116.63, 100.67, 39.25.

[0599] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + 307.1012, measured value [M+H] + = 307.1011.

[0600] FTIR (NEET), CM -1 :3372, 1602, 1568, 1497, 1402, 1214, 984, 820, 777, 692.

[0601] (Preparation example 77: 5-(1-ethyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0602] [ka]

[0603] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.243 mmol) and 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (65 mg, 0.291 mmol). Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 0:100 gradient). The product was obtained as a white solid (60 mg, 81% yield).

[0604] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.72(d,J=5.2Hz,2H), 8.16(d,J=8.5Hz,1H), 8.07(d,J=5.9Hz, 2H), 8.05(s,1H), 8.01(s,2H), 7.51(d,J=8.5Hz,1H), 4.25(q,J=7.3Hz,2H), 1.56(t,J=7.3Hz,3H).

[0605] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.74, 150.02, 149.84, 141.88, 137.66, 1 33.60, 131.52, 131.22, 129.46, 127.41, 123.47, 122.65, 115.88, 47.34, 15.52.

[0606] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1013.

[0607] FTIR (NEET), CM -1 :2925, 1712, 1598, 1577, 1444, 1385, 1209, 993, 958, 828, 812, 791, 643, 561.

[0608] (Preparation example 78: 3-(pyridine-4-yl)-5-(1-(trifluoromethyl)-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0609] [ka]

[0610] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (45 mg, 0.183 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(trifluoromethyl)-1H-pyrazole (57 mg, 0.220 mmol). After 1 hour, an additional [1,1'-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II) (6 mg, 0.05 mmol) was added, and the mixture was refluxed for a further 5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, gradient from 100:0 to 70:30). The product was obtained as an orange solid (44 mg, 70% yield).

[0611] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.76 (dd, J=4.7, 1.8 Hz, 2H), 8.39 (s, 1H), 8.34 (s, 1H) ), 8.28(d,J=8.4Hz,1H), 8.13(s,1H), 8.11(dd,J=4.7,1.8Hz,2H), 7.60(d,J=8.4Hz,1H).

[0612] 13 ¹³C NMR (126MHz, Chloroform-d) δ(ppm) 152.89, 149.18, 147.80, 142.40, 142.05, 133.54, 133.02, 131.78, 130.74, 126.38, 126.12, 122.84, 119.07, 118.03 (apparently a quartet, measured values ​​a doublet, J=263.5Hz).

[0613] 19 F NMR (471MHz, Chloroform-d) δ (ppm) -60.4582.

[0614] HRMS (APCI): Theoretical value (C 16 H 10 F3N4S)[M+H] + =347.0573, measured value [M+H] + =347.0570, FTIR (NEET), CM -1 :3070, 1587, 1556, 1449, 1405, 1382, 1273, 1261, 1205, 1162, 1112, 1066, 993, 951, 886, 822, 761, 553.

[0615] (Preparation example 79: 5-(1-isopropyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0616] [ka]

[0617] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and 1-isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (60 mg, 0.254 mmol). Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a white solid (43 mg, 66% yield).

[0618] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.74(s,2H), 8.18(d,J=8.1Hz,3H), 8.07(s,1H), 8.05 (d,J=13.1Hz,2H), 7.54(d,J=8.5Hz,1H), 4.59(p,J=6.7Hz,1H), 1.59(s,3H), 1.58(s,3H).

[0619] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.67, 150.31, 148.68, 143.00, 137.39, 1 33.17, 131.50, 131.30, 130.13, 125.65, 122.99, 122.95, 116.06, 54.19, 22.91.

[0620] HRMS (APCI): Theoretical value (C 18 H 17 N4S)[M+H] + =321.1168, measured value [M+H] + = 321.1171.

[0621] FTIR (NEET), CM -1 :2977, 1598, 1577, 1537, 1385, 1370, 1257, 1220, 994, 981, 828, 811, 791, 641, 561.

[0622] (Preparation example 80: 5-(1-(tert-butyl)-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0623] [ka]

[0624] To a solution (3-bromo-1-(tert-butyl)-1H-pyrazole (122 mg, 0.600 mmol) dissolved in dioxane (3.8 mL)), bis(pinacolate)diborone (190 mg, 0.675 mmol), potassium acetate (236 mg, 2.40 mmol), tris(dibenzylideneacetone)dipalladium (0) (27 mg, 0.030 mmol), and 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (46 mg, 0.096 mmol) were added, and the reaction mixture was refluxed for 16 hours. Next, 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (184 mg, 0.675 mmol) (Preparation Example 12), tripotassium phosphate (381 mg, 1.80 mmol), dioxane (3 mL), and H2O (0.9 mL) were added, and the reaction mixture was refluxed for 16 hours. Then, [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (44 mg, 0.060 mmol) and additional tripotassium phosphate (381 mg, 1.80 mmol) were added, and the reaction mixture was refluxed for a further 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 40:60) and TLC for preparation (hexane / siRNA, 80:20). The product was obtained as a brown solid (92 mg, 46%).

[0625] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.74(s,2H), 8.37(s,2H), 8.25(d,J=8.5Hz,1H), 8.18 (d,J=8.5Hz,1H), 8.14(s,1H), 7.62(d,J=2.3Hz,1H), 6.99(d,J=2.4Hz,1H), 1.67(s,9H).

[0626] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.27, 151.31, 150.92, 147.51, 144.16, 1 32.72, 132.66, 131.13, 130.44, 127.17, 123.14, 116.66, 103.97, 58.88, 29.92.

[0627] HRMS (APCI): Theoretical value (C 19 H 19 N4S)[M+H] + =335.1325, measured value [M+H] + = 335.1326.

[0628] FTIR (NEET), CM -1 :2976, 1634, 1597, 1572, 1524, 1368, 1239, 1185, 833, 775, 647, 491.

[0629] (Preparation example 81: 5-(1-benzyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0630] [ka]

[0631] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (48 mg, 0.195 mmol) and 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (58 mg, 0.234 mmol). Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10 to 50:50 gradient). The product was obtained as a white solid (60 mg, 84% yield).

[0632] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.72(d,J=4.5Hz,2H), 8.26(d,J=5.7Hz,2H), 8.19(d,J=8.5Hz,1H), 8.13 (s,1H), 8.11(s,1H), 7.99(s,1H), 7.53(d,J=8.5Hz,1H), 7.41~7.34(m,3H), 7.33~7.29(m,2H), 5.40(s,2H).

[0633] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.58, 150.12, 147.47, 144.05, 138.17, 136.04, 132.6 4, 131.67, 131.40, 130.90, 128.94, 128.36, 128.32, 127.87, 123.94, 123.08, 116.23, 56.46.

[0634] HRMS (APCI): Theoretical value (C 22 H 17 N4S)[M+H] + =369.1168, measured value [M+H] + = 369.1166.

[0635] FTIR (NEET), CM -1 :1595, 1573, 1531, 1454, 1397, 1228, 1172, 991, 873, 791, 727, 694, 641, 627, 558.

[0636] (Preparation Example 82: 5-(5-(cyclopropylmethyl)-1-methyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0637] [ka]

[0638] The compounds were prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (45 mg, 0.183 mmol) and 5-(cyclopropylmethyl)-1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (58 mg, 0.234 mmol). Reaction temperature: 85°C. After 16 hours, additional tripotassium phosphate (116 mg, 0.549 mmol), 1,1'-bis(di-tert-phosphino)ferrocene]dichloropalladium(II) (6 mg, 0.009 mmol), and H2O (0.5 mL) were added, and the mixture was refluxed for a further 2.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 20:80 gradient). The product was obtained as a yellow waxy substance (23 mg, 37% yield).

[0639] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.73(s,2H), 8.20(d,J=8.5Hz,1H), 8.13~8.07(m,2H), 8.04(s,1H), 7.91(s,1H) ), 7.61(d,J=8.5Hz,1H), 3.92(s,3H), 3.34~3.19(m,2H), 1.04(s,1H), 0.38(d,J=7.6Hz,2H), 0.09(d,J=5.1Hz,2H).

[0640] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.40, 151.92, 148.07, 143.86, 141.37, 138.09, 133.77, 131.18, 131.06, 130.18, 123.45, 119.21, 117.39, 36.93, 28.29, 10.24, 4.27.

[0641] HRMS (APCI): Theoretical value (C 20 H 19 N4S)[M+H] + =347.1325, measured value [M+H] + = 347.1327.

[0642] FTIR (NEET), CM -1 :1571,1264,827,730,702.

[0643] (Preparation Example 83: tert-butyl(1-methyl-4-(3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)-1H-pyrazole-3-yl)carbamate)

[0644] [ka]

[0645] The compounds were prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (100 mg, 0.406 mmol) and tert-butyl(1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-3-yl)carbamate (157 mg, 0.487 mmol). After 16 hours, additional tripotassium phosphate (125 mg (0.560 mmol) and [1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) (13 mg, 0.020 mmol) were added, and the mixture was refluxed for a further 4 hours. Next, bis(tri-tert-butylphosphine)palladium(O) (10 mg, 0.020 mmol) was added, and the mixture was refluxed for a further 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 100:0 to 95:5 gradient). The product was obtained as a pale yellow waxy substance (59 mg, 36% yield).

[0646] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.66(s,1H), 8.75(d,J=4.7Hz,2H), 8.18(d,J=8.6Hz,1H), 7 .98(s,1H), 7.92(d,J=5.0Hz,2H), 7.72(s,1H), 7.43(d,J=8.6Hz,1H), 3.94(s,3H), 1.38(s,9H).

[0647] 13 C NMR(126MHz,Chloroform-d)δ(ppm)151.72, 151.45, 150.94, 149.77, 146.62, 142.47, 1 34.16, 131.67, 130.97, 130.14, 128.72, 122.74, 116.40, 108.70, 80.56, 39.59, 28.28.

[0648] HRMS (APCI): Theoretical value (C 21 H 22 N5O2S)[M+H] + =408.1489, measured value [M+H] + = 408.1487.

[0649] FTIR (NEET), CM -1 :3289, 2925, 1726, 1580, 1556, 1534, 1388, 1365, 1222, 1153, 1089, 1052, 1052, 1016, 814, 641, 557.

[0650] (Preparation Example 84: 1-Methyl-4-(3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)-1H-pyrazole-3-amine)

[0651] [ka]

[0652] To a solution (dissolved in 0.2 mL of dichloromethane, tert-butyl (1-methyl-4-(3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)-1H-pyrazole-3-yl)carbamate (25 mg, 0.061 mmol)), trifluoroacetic acid (50 μL) was added, and the reaction mixture was stirred at 25°C for 2 hours. Next, an additional 0.1 mL of trifluoroacetic acid was added, and the reaction mixture was stirred at 25°C for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (a gradient of 100:0:0 to 79:19:2 of 7M NH3 in siRNA / methanol / methanol). The product was obtained as a yellow waxy substance (14 mg, 72%).

[0653] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.65(dd,J=4.7,1.4Hz,2H), 8.32(s,1H), 8.28(d,J=8 .6Hz,1H), 8.06(dd,J=4.7,1.5Hz,2H), 8.01(s,1H), 7.60(d,J=8.6Hz,1H), 3.76(s,3H).

[0654] 13 C NMR(126MHz,Methanol-d4)δ(ppm)155.69, 153.35, 152.73, 150.10, 145.31, 134.53, 132.68, 132.14, 131.82, 131.59, 124.62, 117.07, 107.67, 38.66.

[0655] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + =308.0964, measured value [M+H] + =308.0962.

[0656] FTIR (NEET), CM -1 :3656~2258, 1673, 1556, 1388, 1173, 1122, 826, 799, 643.

[0657] (Preparation example 85: 3-(pyridine-4-yl)-5-(1,3,5-trimethyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0658] [ka]

[0659] To the solution (dioxane (3 mL) in which 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (155 mg, 0.629 mmol) was dissolved), (1,3,5-trimethyl-1H-pyrazole-4-yl)boronic acid (92 mg, 0.755 mmol), potassium carbonate (261 mg, 1.88 mmol), SPhosPdG3 (0.063 mmol, 49 mg), Sphos (13 mg, 0.032 mmol), and H2O (1 mL) were added, and the reaction mixture was refluxed for 16 hours. Then, additional SPhosPdG3 (0.063 mmol, 49 mg) and potassium carbonate (125 mg, 0.904 mmol) were added, and the reaction mixture was refluxed for a further 24 hours. The solvent was evaporated, and the residue was purified twice with a gradient of dichloromethane / methanol (100:0 to 95:5) followed by a gradient of hexane / Âde (70:30 to 50:50). The product was obtained as a white solid (69 mg, 34%).

[0660] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.69(dd,J=4.6,1.6Hz,2H), 8.24(d,J=8.5Hz,1H),8.08~8.07 (dd,J=4.6,1.5Hz,2H), 8.06(s,1H), 7.40(d,J=8.5Hz,1H), 3.81(s,3H), 2.49(s,3H), 2.45(s,3H).

[0661] 13C NMR (126MHz, Chloroform-d) δ (ppm) 152.84, 151.99, 149.59, 145.86, 142.15, 138. 29, 133.96, 131.12, 130.90, 129.47, 122.80, 119.35, 118.45, 35.99, 13.58, 11.07.

[0662] HRMS (APCI): Theoretical value (C 18 H 17 N4S)[M+H] + =321.1168, measured value [M+H] + = 321.1167.

[0663] FTIR (NEET), CM -1 :3045, 3196, 3046, 2925, 2853, 1662, 1598, 1570, 1433, 1385, 1249, 1083, 993, 858, 813, 640, 587, 573, 553, 480, 453.

[0664] (Preparation example 86: 5-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0665] [ka]

[0666] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (51 mg, 0.243 mmol). Reaction time: 1 hour. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 40:60 to 0:100 gradient). The product was obtained as an orange solid (53 mg, 89% yield).

[0667] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.73(d,J=5.0Hz,2H), 8.24(d,J=8.5Hz,1H), 8.18(d,J=5.6Hz, 2H), 8.09(d,J=8.5Hz,1H), 8.07(s,1H), 7.45(d,J=2.2Hz,1H), 7.03(d,J=2.2Hz,1H), 4.01(s,3H).

[0668] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.50, 152.14, 150.42, 149.55, 142.21, 133.62, 132.90, 131.64, 131.21, 129.46, 122.73, 116.06, 104.97, 39.27.

[0669] HRMS (APCI): Theoretical value (C 16 H 13 N4S)[M+H] + =293.0855, measured value [M+H] + =293.0854.

[0670] FTIR (NEET), CM -1 :3098, 1594, 1571, 1558, 1511, 1383, 1266, 1236, 992, 844, 795, 776, 765, 723, 639, 591, 557, 477, 439.

[0671] (Preparation example 87: 5-(1-ethyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0672] [ka]

[0673] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and 1-ethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (50 mg, 0.223 mmol). Reaction time: 2.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 40:60 to 20:80 gradient) and preparation TLC (cyclohexane / siRNA, 90:10, double elution). The product was obtained as a yellow waxy substance (37 mg, 62% yield).

[0674] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.74(s,2H), 8.23(d,J=8.5Hz,1H), 8.16(s,2H), 8.10(d,J=8.5Hz,1H) ), 8.04(s,1H), 7.48(d,J=1.9Hz,1H), 7.03(d,J=1.9Hz,1H), 4.27(q,J=7.3Hz,2H), 1.57(t,J=7.3Hz,3H).

[0675] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.50, 151.85, 150.57, 149.86, 141.89, 1 33.72, 132.82, 131.12, 129.82, 129.19, 122.71, 116.11, 104.68, 47.34, 15.62.

[0676] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1011.

[0677] FTIR (NEET), CM -1:2979, 2933, 1596, 1570, 1557, 1432, 1384, 1355, 1324, 1263, 1266, 1039, 994, 828, 775, 761, 733, 641, 592.

[0678] (Preparation example 88: 5-(1-phenyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0679] [ka]

[0680] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and 1-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (60 mg, 0.223 mmol). Reaction time: 2.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 70:30 to 50:50 gradient). The product was obtained as a white solid (57 mg, 79% yield).

[0681] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.68(dd,J=4.6,1.5Hz,2H), 8.29(s,2H), 8.12(dd,J=4.5,1.5Hz,2H), 8.07(s,1 H), 8.03(d,J=2.4Hz,1H), 7.82(dd,J=8.8,1.1Hz,2H), 7.52~7.48(m,2H), 7.34~7.31(m,1H), 7.27(d,J=2.5Hz,1H).

[0682] 13C NMR(126MHz,Chloroform-d)δ(ppm)153.59, 152.55, 150.04, 141.77, 140.19, 133.84 , 133.32, 131.24, 129.49, 129.32, 128.27, 126.66, 122.67, 119.22, 116.35, 106.90.

[0683] HRMS (APCI): Theoretical value (C 21 H 15 N4S)[M+H] + =355.1012, measured value [M+H] + = 355.1009.

[0684] FTIR (NEET), CM -1 :3039, 1598, 1570, 1518, 1382, 1273, 830, 756, 690, 643.

[0685] (Preparation example 89: 5-(1-benzyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0686] [ka]

[0687] To a solution (100 mg, 0.421 mmol) of 1-benzyl-3-bromo-1H-pyrazole dissolved in 3.5 mL of dioxane), bis(pinacolate)diborone (133 mg, 0.526 mmol), potassium acetate (165 mg, 1.68 mmol), tris(dibenzylideneacetone)dipalladium (0) (19 mg, 0.021 mmol), and Xphos (32 mg, 0.067 mmol) were added, and the reaction mixture was refluxed for 5 hours. Next, 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (129 mg, 0.526 mmol) (Preparation Example 12), tripotassium phosphate (268 mg, 1.26 mmol), dioxane (3 mL), and H2O (0.9 mL) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 100:0:0 to 0:90:10 gradient). The product was obtained as a white solid (87 mg, 56%).

[0688] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.68(d,J=6.1Hz,2H), 8.19(d,J=8.5Hz,1H), 8.13~8.11(m,2H), 8.09(d,J=8.5Hz,1H), 8.01( s,1H), 7.41(d,J=2.3Hz,1H), 7.36~7.25(m,3H), 7.24(d,J=1.4Hz,1H), 7.22(d,J=2.5Hz,1H), 7.03(d,J=2.3Hz,1H), 5.37(s,2H).

[0689] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.43, 152.18, 150.39, 149.57, 142.09, 136.38, 133.5 4, 132.91, 131.13, 130.96, 129.40, 128.81, 128.08, 127.61, 122.66, 116.24, 105.32, 56.31.

[0690] HRMS (APCI): Theoretical value (C 22 H 17N4S)[M+H] + =369.1168, measured value [M+H] + =369.1167.

[0691] FTIR (NEET), CM -1 :1596, 1572, 1382, 1231, 1053, 1043, 838, 789, 774, 717, 694, 641.

[0692] (Preparation example 90: 5-(1-methyl-1H-pyrazole-5-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0693] [ka]

[0694] The compounds were prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (45 mg, 0.183 mmol) and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (46 mg, 0.220 mmol). Reaction temperature: 85°C. After 16 hours, additional tripotassium phosphate (116 mg, 0.549 mmol), 1,1'-bis(di-tert-phosphino)ferrocene]dichloropalladium(II) (6 mg, 0.009 mmol), and H2O (0.5 mL) were added, and the mixture was refluxed for a further 2.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 70:30 to 20:80 gradient) and TLC for preparation (hexane / siRNA, 20:80, single elution, and 50:50, single elution). The product was obtained as a white solid (11 mg, 21% yield).

[0695] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.75(d,J=4.9Hz,2H), 8.33(d,J=8.5Hz,1H), 8.23(s,1H), 8.22(s,2H), 7.70(d,J=8.5Hz,1H), 7.70(d,J=8.5Hz,1H), 6.71(d,J=1.6Hz,1H), 4.26(s,3H).

[0696] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.02, 148.06, 146.92, 144.57, 140.89, 138.29, 133.12, 132.99, 131.93, 131.85, 123.43, 119.13, 107.38, 39.89.

[0697] HRMS (APCI): Theoretical value (C 16 H 13 N4S)[M+H] + =293.0855, measured value [M+H] + = 293.0858.

[0698] FTIR (NEET), CM -1 :3398, 3097, 2924, 1598, 1571, 1556, 1390, 999, 928, 828, 782, 641.

[0699] (Preparation Example 91: 5-(1-methyl-1H-imidazole-5-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0700] [ka]

[0701] The compound was prepared using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.244 mmol) and 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole (61 mg, 0.293 mmol) according to general procedure B. After 6 hours, an additional [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (14 mg, 0.019 mmol) and triethylamine (102 μL, 0.732 mmol) instead of potassium phosphate were added, and the mixture was refluxed for a further 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / Âxy / methanol, 70:30:0 to 0:95:5 gradient) and TLC for preparation (dichloromethane / methanol, 90:10). The product was obtained as a brown solid (18 mg, 13% yield).

[0702] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.71(d,J=6.0Hz,2H), 8.23(d,J=8.6Hz,1H), 8.01(s, 1H), 7.91(d,J=6.0Hz,2H), 7.66(d,J=8.6Hz,1H), 7.58(s,1H), 7.55(s,1H), 4.04(s,3H).

[0703] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.17, 149.92, 148.22, 141.98, 141.35, 134.48, 131.96, 131.63, 131.51, 131.19, 129.67, 122.98, 117.61, 35.07.

[0704] HRMS (APCI): Theoretical value (C 16 H 13 N4S)[M+H] + =293.0855, measured value [M+H] + =293.0853.

[0705] FTIR (NEET), CM -1:3380, 3096, 1716, 1598, 1572, 1393, 1231, 1177, 1129, 1075, 827, 658, 641.

[0706] (Preparation example 92: 5-(isothiazol-5-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0707] [ka]

[0708] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (45 mg, 0.182 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isothiazole (46 mg, 0.218 mmol), and XPhosPdG3 (15 mg, 0.018 mmol) instead of [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 70:30 to 30:70 gradient). The product was obtained as a pale yellow solid (12 mg, 22% yield).

[0709] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.66(d,J=5.3Hz,2H), 8.60(s,1H), 8.56(d,J=1.8Hz,1H), 8 .52(d,J=8.4Hz,1H), 8.28(dd,J=4.6,1.7Hz,2H), 7.95(d,J=8.5Hz,1H), 7.92(d,J=1.9Hz,1H).

[0710] 13 C NMR(126MHz,Methanol-d4)δ(ppm)169.64,160.02,153.91,150.25,148.77,143.77,136.30,134.11,133.88,133.54,124.06,121.98,116.86.

[0711] HRMS (APCI): Theoretical value (C 15 H 10 N3S2)[M+H] + =296.0311, measured value [M+H] + =296.0311.

[0712] FTIR (NEET), CM -1 :3045, 2957, 2853, 1599, 1557, 1387, 812, 784, 637.

[0713] (Preparation example 93: 5-(1-methyl-1H-1,2,3-triazol-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0714] [ka]

[0715] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) dissolved in dioxane (4.5 mL)), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2,3-triazole (58 mg, 0.278 mmol), potassium carbonate (96 mg, 0.696 mmol), SPhosPdG3 (0.028 mmol, 22 mg), Sphos (7 mg, 0.009 mmol), and H2O (1.1 mL) were added, and the reaction mixture was refluxed for 4.5 hours. Next, an additional tripotassium phosphate (116 g, 0.546 mmol) was added, and the reaction mixture was refluxed for a further 5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 50:50 to 0:100 gradient) and TLC for preparation (hexane / siRNA, 20:80). The product was obtained as a pale yellow solid (14 mg, 20%).

[0716] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.75(d,J=4.9Hz,2H), 8.32(d,J=8.5Hz,1H), 8 .29(d,J=8.5Hz,1H), 8.19(s,1H), 8.08(s,1H), 8.06(d,J=6.1Hz,2H), 4.22(s,3H).

[0717] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.49, 149.66, 148.94, 148.42, 142.11, 133.59, 133.46, 131.66, 130.03, 123.23, 122.79, 116.39, 100.00, 36.91.

[0718] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H] + =294.0808, measured value [M+H] + =294.0806.

[0719] FTIR (NEET), CM -1 :3401, 3080, 1627, 1597, 1519, 1389, 1220, 1199, 1056, 832, 803.

[0720] (Preparation example 94: 5-(2-methyl-2H-1,2,3-triazol-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0721] [ka]

[0722] The compound was prepared using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (55 mg, 0.223 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (56 mg, 0.267 mmol) according to general procedure B. Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 60:40 to 0:100 gradient). The product was obtained as a pale yellow solid (59 mg, 91% yield).

[0723] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.75(s,2H), 8.29(d,J=8.5Hz,1H), 8.23(s,1H), 8.11(d,J=5.9Hz,2H), 8.09(s,1H), 8.01(d,J=8.5Hz,1H), 4.29(s,3H).

[0724] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.60, 149.87, 148.34, 147.88, 141.73, 133.74, 133.58, 133.17, 131.60, 129.93, 122.64, 116.46, 41.93.

[0725] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H] + =294.0808, measured value [M+H] + =294.0807.

[0726] FTIR (NEET), CM -1 :3076, 1602, 1573, 1388, 1370, 1012, 991, 827, 800, 712, 642, 593, 555.

[0727] (Preparation example 95: 5-(1-methyl-1H-1,2,3-triazol-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0728] [ka]

[0729] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2,3-triazole (51 mg, 0.244 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient). The product was obtained as a pale yellow solid (43 mg, 73% yield).

[0730] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.76(s,2H), 8.32(d,J=8.5Hz,1H), 8.28(d,J=8.5Hz,1H), 8.19(s,1H), 8.08(m,3H), 4.21(s,3H).

[0731] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.47, 149.53, 148.92, 148.42, 142.18, 133.52, 133.45, 131.65, 130.09, 123.24, 122.85, 116.38, 36.90.

[0732] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H] + =294.0808, measured value [M+H] + =294.0811.

[0733] FTIR (NEET), CM -1 :1593, 1578, 1388, 1234, 1198, 1068, 870, 855, 832, 791, 641, 591, 482.

[0734] (Preparation example 96: 5-(1-methyl-1H-1,2,4-triazol-5-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0735] [ka]

[0736] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (60 mg, 0.243 mmol) dissolved in dioxane (3 mL)), 1-methyl-5-(tributylstanyl)-1H-1,2,4-triazole (102 μL, 0.316 mmol) and bis(tri-tert-butylphosphine)palladium(0) (10 mg, 0.019 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / cyclohexane / methanol, gradient from 70:30:0 to 95:0:5). The product was obtained as a white solid (31 mg, 44%).

[0737] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.66(dd,J=4.6,1.6Hz,2H), 8.62(d,J=8.5Hz,1H), 8. 56(s,1H), 8.22(d,J=8.5Hz,1H), 8.14(dd,J=4.7,1.5Hz,2H), 8.03(s,1H), 4.38(s,3H).

[0738] 13 C NMR (126MHz, Methanol-d4) δ (ppm) 153.36, 153.30, 150.95, 150.38, 146.44, 144.09, 136.76, 134.76, 134.08, 133.89, 124.59, 120.26, 39.68.

[0739] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H]+ =294.0808, measured value [M+H] + =294.0810.

[0740] FTIR (NEET), CM -1 :1601, 1470, 1386, 1360, 1272, 1262, 1169, 1080, 1061, 873, 774, 741, 698, 639, 512, 488.

[0741] (Preparation Example 97: N-(1-methyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0742] [ka]

[0743] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and 1-methyl-1H-pyrazole-4-amine (24 mg, 0.244 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 80:20:0 to 0:98:2 gradient). The product was obtained as an orange solid (29 mg, 47% yield).

[0744] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.71(dd,J=4.5,1.7Hz,2H), 7.97(dd,J=4.5,1.6Hz,2H),7. 94(d,J=8.7Hz,1H), 7.89(s,2H), 7.46(s,1H), 6.68(d,J=8.9Hz,1H), 6.29(s,1H), 3.89(s,3H).

[0745] 13C NMR (126MHz, Chloroform-d) δ (ppm) 154.52, 151.62, 149.85, 142.55, 133.28, 132.08, 132.00, 128.66, 124.86, 123.26, 122.96, 122.90, 107.23, 39.26.

[0746] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + =308.0964, measured value [M+H] + =308.0962.

[0747] FTIR (NEET), CM -1 :1603, 1577, 1452, 1406, 1389, 1349, 999, 757, 638, 563, 451.

[0748] (Preparation Example 98: N-(1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0749] [ka]

[0750] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (70 mg, 0.284 mmol) dissolved in tert-butanol (2.4 mL)), potassium carbonate (78 mg, 0.568 mmol), tert-butyl 4-amino-1H-pyrazole-1-carboxylate (62 mg, 0.342 mmol), and BrettPhosPdG3 (25 mg, 0.028 mmol) were added, and the reaction mixture was stirred at 85°C for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, gradient from 80:20:0 to 0:95:5) and TLC for preparation (siRNA / methanol, 95:5). The product was obtained as a white solid (7 mg, 11%).

[0751] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.63(d,J=4.1Hz,2H), 8.20(s,1H), 8.18(d,J=6.3Hz,2H), 8.03(d,J=8.9Hz,1H), 7.69(s,2H), 6.80(d,J=8.9Hz,1H).

[0752] 13 C NMR (126MHz, Methanol-d4) δ (ppm) 155.86, 152.63, 150.09, 145.40, 133.80, 132.75, 130.49, 125.51, 124.44, 109.87.

[0753] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H] + =294.0808, measured value [M+H] + = 294.0809.

[0754] FTIR (NEET), CM -1 :2920, 2852, 2027, 1980, 1606, 1576, 1454, 1386, 1285, 1009, 789, 777, 693.

[0755] (Preparation Example 99: N-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0756] [ka]

[0757] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and 1-methyl-1H-pyrazole-3-amine (21 μL, 0.244 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:98:2 gradient). The product was obtained as a pale yellow solid (38 mg, 61% yield).

[0758] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.70(d,J=6.3Hz,2H), 8.04(d,J=4.7Hz,2H), 8.02(d,J=8. 9Hz,1H), 7.94(s,1H), 7.28(d,J=2.3Hz,1H), 7.16(s,1H), 6.47(d,J=2.3Hz,1H), 3.84(s,3H).

[0759] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 166.29, 160.42, 153.24, 149.40, 149.16, 142.69, 132.32, 130.77, 129.08, 125.61, 122.84, 108.25, 96.41, 38.83.

[0760] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + =308.0964, measured value [M+H] + =308.096.

[0761] FTIR (NEET), CM -1 :3098, 2923, 1596, 1572, 1536, 1518, 1481, 1406, 1390, 1351, 1312, 1293, 779, 737, 697, 640.

[0762] (Preparation Example 100: N-methyl-N-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0763] [ka]

[0764] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.243 mmol) and N,1-dimethyl-1H-pyrazole-3-amine hydrochloride (43 mg, 0.292 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50:0 to 0:100:0 gradient). The product was obtained as a pale yellow solid (19 mg, 24% yield).

[0765] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.68(d,J=5.4Hz,2H), 8.12(dd,J=4.6,1.6Hz,2H)7.95(s,1H),7.89(d, J=9.0Hz,1H), 7.33(d,J=2.3Hz,1H), 7.15(d,J=9.1Hz,1H), 6.17(d,J=2.3Hz,1H), 3.89(s,3H), 3.60(s,3H).

[0766] 13 C NMR(126MHz,Chloroform-d)δ(ppm)156.28, 153.94, 151.28, 149.84, 142.25, 1 32.81, 131.23, 130.88, 128.29, 124.73, 122.33, 108.32, 99.53, 39.16, 37.44.

[0767] HRMS (APCI): Theoretical value (C 17 H 16 N5S)[M+H] + =322.1121, measured value [M+H] +=322.1124.

[0768] FTIR (NEET), CM -1 :3402, 3097, 2927, 1597, 1579, 1525, 1449, 1389, 1343, 827, 783, 756, 686, 591.

[0769] (Preparation Example 101: N-(1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0770] [ka]

[0771] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (70 mg, 0.284 mmol) and tert-butyl 3-amino-1H-pyrazole-1-carboxylate (62 mg, 0.308 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 100:0 to 95:5 gradient). The product was obtained as a white solid (17 mg, 20% yield).

[0772] 1 H NMR(500MHz,DMSO-d6)δ(ppm)12.14(s,1H), 9.54(s,1H), 8.68~8.65(m,2H), 8.48(s,1H), 8. 22(d,J=8.9Hz,1H), 8.18(d,J=3.5Hz,1H), 7.63(s,1H), 7.22(d,J=8.9Hz,1H), 6.65(s,1H).

[0773] 13 C NMR(126MHz,DMSO-d6)δ(ppm)153.71, 150.84, 149.65, 141.67, 132.16, 131.72 , 129.98, 128.36, 123.91, 122.22, 108.76, 95.22, 79.19, 79.13, 78.92, 78.66.

[0774] HRMS (APCI): Theoretical value (C 15 H 12 N5S)[M+H] + =294.0808, measured value [M+H] + =294.0806.

[0775] FTIR (NEET), CM -1 :3270~2928, 1602, 1580, 1484, 1390, 778, 638.

[0776] (Preparation Example 102: N-(1,5-dimethyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0777] [ka]

[0778] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (80 mg, 0.325 mmol) and 1,5-dimethyl-1H-pyrazole-3-amine (43 mg, 0.390 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / Â1 / methanol, 50:50:0 to 0:95:5 gradient). The product was obtained as a white solid (43 mg, 41% yield).

[0779] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.57(dd,J=4.7,1.6Hz,2H), 8.25(s,1H), 8.23(dd,J=4.7,1 .7Hz,2H), 8.06(d,J=8.9Hz,1H), 7.05(d,J=8.9Hz,1H), 6.43(s,1H), 3.70(s,3H), 2.28(s,3H).

[0780] 13C NMR(126MHz,Methanol-d4)δ(ppm)155.33, 152.55, 149.93, 149.65, 144.95, 1 40.98, 133.36, 133.09, 130.88, 126.44, 124.33, 109.64, 97.98, 35.52, 11.18.

[0781] HRMS (APCI): Theoretical value (C 17 H 16 N5S)[M+H] + =322.1121, measured value [M+H] + =322.1124.

[0782] FTIR (NEET), CM -1 :3263, 3065, 3037, 2935, 1600, 1580, 1484, 1390, 851, 780, 734, 637.

[0783] (Preparation Example 103: tert-butyl(1-methyl-3-((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)-amino)-1H-pyrazole-5-yl)carbamate)

[0784] [ka]

[0785] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (70 mg, 0.284 mmol) and tert-butyl(3-amino-1-methyl-1H-pyrazole-5-yl)carbamate (72 mg, 0.341 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 0:100 gradient). The product was obtained as a white solid (13 mg, 13% yield).

[0786] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.69(dd,J=4.7,1.4Hz,2H), 7.99(dd,J=4.6,1.6Hz,2H),7. 97(d,J=8.8Hz,1H), 7.89(s,1H), 7.08(d,J=9.8Hz,1H), 6.48(s,2H), 3.67(s,3H), 1.54(s,9H).

[0787] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 153.16, 151.42, 149.95, 147.61, 142.25, 135. 94, 133.22, 132.14, 128.70, 125.65, 122.72, 108.11, 90.66, 81.79, 34.93, 28.23.

[0788] HRMS (APCI): Theoretical value (C 21 H 23 N6O2S)[M+H] + =423.1598, measured value [M+H] + = 423.1598.

[0789] FTIR (NEET), CM -1 :2976, 2928, 1716, 1601, 1578, 1389, 1246, 1156, 907, 779, 729, 641.

[0790] (Preparation Example 104: 1-Methyl-N3-(3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)-1H-pyrazole-3,5-diamine)

[0791] [ka]

[0792] The compound was prepared using tert-butyl(1-methyl-3-((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)-amino)-1H-pyrazole-5-yl)carbamate (Preparation Example 103) (14 mg, 0.033 mmol) according to general procedure D. After 5 hours, an additional 4N HCl in dioxane (100 μL, 0.792 mmol) was added, and the mixture was refluxed for a further 5 hours. The solvent was evaporated, and the residue was purified by preparation TLC (dichloromethane / methanol / 7M NH3 in methanol, 90:5:5). The product was obtained as a pale yellow solid (8 mg, 71% yield).

[0793] 1 H NMR(500MHz,DMSO-d6)δ(ppm)9.15(s,1H), 8.69(dd,J=4.3,1.4Hz,2H), 8.51(s,1H), 8.25(dd,J= 4.8,1.5Hz,2H), 8.18(d,J=9.0Hz,1H), 7.30(d,J=8.9Hz,1H), 5.17(d,J=2.4Hz,2H), 3.46(s,3H).

[0794] 13 C NMR(126MHz,DMSO-d6)δ(ppm)153.64, 150.94, 149.79, 147.24, 146.68, 146. 61, 141.46, 132.01, 131.37, 129.89, 123.72, 121.88, 108.73, 79.66, 33.61.

[0795] HRMS (APCI): Theoretical value (C 16 H 15 N6S)[M+H] + =323.1073, measured value [M+H] + = 323.1076.

[0796] FTIR (NEET), CM -1 :3564~2999, 1634, 1604, 1582, 1563, 1507, 1485, 1393, 783, 640.

[0797] (Preparation Example 105: Ethyl 1-methyl-3-((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)amino)-1H-pyrazole-5-carboxylate)

[0798] [ka]

[0799] To the solution (111 mg, 0.537 mmol) of ethyl 3-amino-1-methyl-1H-pyrazole-5-carboxylate hydrochloride dissolved in 1 mL of dioxane), 120 mg, 0.366 mmol was added, and the reaction mixture was stirred at room temperature for 30 minutes. Next, 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.244 mmol), cesium carbonate (198 mg, 0.610 mmol), bis(dibenzylideneacetone)palladium (0) (7 mg, 0.0081 mmol), 4,5-bis(diphenylphosphin)-9,9-dimethylxanthene (9 mg, 0.016 mmol), and 2 mL of dioxane were added, and the mixture was refluxed for 16 hours. Subsequently, triethylamine (0.5 mL) was added, and the mixture was refluxed for a further 24 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / Âr, 90:10 to 50:50 gradient). The product was obtained as a pale yellow solid (35 mg, 38%).

[0800] 1 H NMR(500MHz,Chloroform-d3)δ(ppm)8.71(dd,J=4.5,1.5Hz,2H), 8.01(d,J=6.1Hz,1H), 7.99(dd,J=3.1,1.3Hz,2H), 7 .92(s,1H), 7.27(s,1H), 7.11(s,1H), 6.91(d,J=8.8Hz,1H), 4.41(q,J=7.1Hz,2H), 4.12(s,3H), 1.42(t,J=7.1Hz,3H).

[0801] 13C NMR(126MHz,Chloroform-d3)δ(ppm)159.92, 152.62, 151.42, 150.00, 147.42, 142.20, 133.45, 132.72, 132.22, 128.76, 125.82, 122.77, 108.22, 100.88, 61.17, 38.90, 14.42.

[0802] HRMS (APCI): Theoretical value (C 19 H 18 N5O2S2)[M+H] + =380.1176, measured value [M+H] + =380.1174.

[0803] FTIR (NEET), CM -1 :2956, 2922, 2850, 1717, 1599, 1581, 1550, 1482, 1454, 1389, 1258, 1098, 801, 763.

[0804] (Preparation Example 106: N-(1-methyl-4-(methylthio)-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0805] [ka]

[0806] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.244 mmol) and 1-methyl-4-(methylthio)-1H-pyrazole-3-amine (42 mg, 0.295 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10 to 30:70 gradient). The product was obtained as an orange solid (20 mg, 23% yield).

[0807] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.71(dd,J=4.5,1.5Hz,2H), 8.11(d,J=1.2Hz,2H),8.0 6(dd,J=4.5,1.5Hz,2H), 7.95(s,1H), 7.38(s,1H), 7.35(s,1H), 3.86(s,3H), 2.25(s,3H).

[0808] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.72, 151.35, 151.06, 150.03, 141.96, 1 34.45, 132.81, 132.50, 129.03, 126.42, 122.52, 108.03, 99.17, 39.25, 21.28.

[0809] HRMS (APCI): Theoretical value (C 17 H 16 N5S2)[M+H] + =354.0842, measured value [M+H] + =354.0841.

[0810] FTIR (NEET), CM -1 :3397, 3048, 3028, 2915, 1601, 1578, 1542, 1392, 1159, 994, 963, 817, 806, 714, 678, 516, 494.

[0811] (Preparation Example 107: Ethyl 1-methyl-3-((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)amino)-1H-pyrazole-4-carboxylate)

[0812] [ka]

[0813] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (150 mg, 0.609 mmol) and ethyl 3-amino-1-methyl-1H-pyrazole-4-carboxylate (124 mg, 0.730 mmol). Reaction time: 1 hour. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 20:80 to 0:100 gradient). The product was obtained as a white solid (220 mg, 95% yield).

[0814] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.85(s,1H), 8.70(dd,J=4.6,1.8Hz,2H), 8.14(s,2H), 8.12(dd,J =4.7,1.6Hz,2H), 7.99(s,1H), 7.73(s,1H), 4.35(q,J=7.1Hz,2H), 3.89(s,3H), 1.41(t,J=7.1Hz,3H).

[0815] 13 C NMR(126MHz,Chloroform-d)δ(ppm)163.93, 151.99, 151.50, 151.46, 150.00, 141.83, 1 32.91, 132.76, 132.44, 129.00, 126.76, 122.38, 108.76, 100.09, 60.19, 39.44, 14.37.

[0816] HRMS (APCI): Theoretical value (C 19 H 18 N5O2S)[M+H] + 380.1176, measured value [M+H] + = 380.1175.

[0817] FTIR (NEET), CM -1 :3411, 1705, 1577, 1557, 1396, 1250, 1106, 810, 767, 558.

[0818] (Preparation Example 108: N-((1-methyl-1H-pyrazole-3-yl)methyl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0819] [ka]

[0820] The compound was prepared using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and (1-methyl-1H-pyrazole-3-yl)methaneamine (27 mg, 0.243 mmol) according to general procedure C. After 7 hours, additional cesium carbonate (102 mg, 0.312 mmol), tris(dibenzylideneacetone)dipalladium (7 mg, 0.008 mmol), and 4,5-bis(diphenylphosphin)-9,9-dimethylxanthene (9 mg, 0.008 mmol) were added, and the mixture was refluxed for a further 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (Âxy / methanol, 100:0 to 95:5 gradient) and TLC for preparation (Âxy / methanol, 100:0, single elution, and 95:5, single elution). The product was obtained as a pale yellow solid (7 mg, yield 11%).

[0821] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.66(d,J=6.3Hz,2H), 8.09(d,J=6.3Hz,2H), 7.90(s,1H), 7.86(d,J=8.8Hz,1H), 7.28 (d,J=2.2Hz,1H), 6.58(d,J=8.9Hz,1H), 6.22(d,J=2.1Hz,1H), 5.13(t,J=5.3Hz,1H), 4.66(d,J=5.2Hz,2H), 3.88(s,3H).

[0822] 13C NMR(126MHz,Chloroform-d)δ(ppm)156.70, 151.63, 150.44, 149.80, 142.24, 1 32.57, 131.56, 130.91, 128.08, 124.00, 122.32, 107.42, 104.41, 40.11, 38.76.

[0823] HRMS (APCI): Theoretical value (C 17 H 16 N5S)[M+H] + =322.1121, measured value [M+H] + = 322.1122.

[0824] (Preparation Example 109: 5-((1-methyl-1H-pyrazole-3-yl)oxy)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0825] [ka]

[0826] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.244 mmol) dissolved in toluene (1.5 mL)), tert-butoxide sodium (26 mg, 0.268 mmol), 1-methyl-1H-pyrazole-3-thiol (28 mg, 0.244 mmol), and Josiphos SL-Pd-G3 (9 mg, 0.010 mmol) were added, and the reaction mixture was stirred at room temperature for 6 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 0:100 gradient). The product was obtained as a pale yellow solid (17 mg, 21%).

[0827] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.59(d,J=5.2Hz,2H), 8.02(s,1H), 8.00(d,J=8.5Hz,1H), 7.91 (d,J=6.3Hz,2H), 7.55(d,J=2.2Hz,1H), 7.18(d,J=8.6Hz,1H), 6.59(d,J=2.2Hz,1H), 4.01(s,3H).

[0828] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 158.33, 152.68, 149.36, 141.65, 139.54, 132.74, 131.84, 131.01, 130.91, 129.58, 122.38, 117.29, 113.43, 39.59.

[0829] HRMS (APCI): Theoretical value (C 16 H 13 N4S2)[M+H] + =325.0576, measured value [M+H] + =325.0574.

[0830] FTIR (NEET), CM -1 :3438, 3094, 2931, 1633, 1598, 1560, 1384, 1362, 1150, 1127, 856, 829, 794, 644, 553.

[0831] (Preparation Example 110: 5-((1-methyl-1H-pyrazole-3-yl)oxy)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0832] [ka]

[0833] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) dissolved in DMF (0.8 mL)), cesium carbonate (93 mg, 0.284 mmol), 1-methyl-1H-pyrazole-3-ol (20 mg, 0.203 mmol), copper(I) cyanide (1 mg, 0.010 mmol), and ethylenediamine (5 μL, 0.075 mmol) were added, and the reaction mixture was refluxed for 16 hours. The reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (2 × 15 mL). The integrated organic extract was washed with water (2 × 20 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 0:100 gradient) and TLC for preparation (toluene / methanol, 97:3). The product was obtained as a pale yellow waxy substance (14 mg, 22%).

[0834] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.60(d,J=5.1Hz,2H), 8.18(d,J=8.7Hz,1H), 8.04(d,J=0.5Hz,1H), 7. 94(dd,J=4.6,1.5Hz,2H), 7.36(d,J=2.3Hz,1H), 7.11(d,J=8.4Hz,1H), 6.20(d,J=2.3Hz,1H), 3.88(s,3H).

[0835] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 161.02, 157.54, 150.31, 149.78, 141.39, 133.85, 132.92, 130.93, 129.48, 129.23, 122.29, 108.97, 96.47, 39.24.

[0836] HRMS (APCI): Theoretical value (C 16 H 13 N4OS)[M+H] + =309.0805, measured value [M+H] + =309.0807.

[0837] FTIR (NEET), CM -1 :1630, 1600, 1579, 1561, 1385, 1337, 1263, 1219, 1168, 995, 795, 754, 626, 561, 486, 461.

[0838] (Preparation Example 111: 5-(pyridine-2-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0839] [ka]

[0840] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) dissolved in dioxane (3 mL)), 2-(tributylstanyl)pyridine (85 μL, 0.263 mmol) and bis(tri-tert-butylphosphine)palladium (0) (8 mg, 0.016 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 50:50 gradient). The product was obtained as a white solid (17 mg, 29%).

[0841] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.77(dd,J=4.9,1.5Hz,2H), 8.72(d,J=5.8Hz,1H), 8.57(dd,J=8.2,3. 8Hz,2H), 8.36(d,J=8.5Hz,1H), 8.12(dd,J=4.6,1.6Hz,2H), 8.08(s,1H), 7.88(td,J=7.7,1.8Hz,1H), 7.35 (ddd,J=7.6,4.8,1.3Hz,1H).

[0842] 13C NMR(126MHz,Chloroform-d)δ(ppm)156.22, 154.23, 152.45, 150.10, 149.16, 14 1.79, 137.06, 134.56, 134.10, 131.63, 129.74, 123.91, 122.76, 121.26, 117.02.

[0843] HRMS (APCI): Theoretical value (C 17 H 12 N3S)[M+H] + =290.0746, measured value [M+H] + =290.0746.

[0844] FTIR (NEET), CM -1 :3057, 3075, 1632, 1598, 1542, 1470, 1435, 1389, 1176, 1144, 992, 806, 783, 768, 639, 495.

[0845] (Preparation Example 112: 3-(pyridine-4-yl)-5-(pyrimidine-2-yl)thieno[3,2-b]pyridine)

[0846] [ka]

[0847] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.244 mmol) dissolved in dioxane (3.5 mL)), 2-(tributylstanyl)pyrimidine (100 μL, 0.317 mmol) and bis(tri-tert-butylphosphine)palladium (0) (8 mg, 0.016 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:90:10 gradient) and preparation TLC (toluene:methanol, 95:5, elution twice). The product was obtained as a white solid (30 mg, 43%).

[0848] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.97(d,J=4.9Hz,2H), 8.75(dd,J=4.6,1.8Hz,2H), 8.56(d,J= 8.5Hz,1H), 8.41(d,J=8.5Hz,1H), 8.20(dd,J=4.7,1.7Hz,2H), 8.13(s,1H), 7.35(t,J=4.8Hz,1H).

[0849] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 164.12, 157.73, 153.17, 153.06, 150.28, 141.53, 135.64, 134.43, 131.61, 130.09, 122.56, 120.34, 119.37.

[0850] HRMS (APCI): Theoretical value (C 16 H 11 N4S)[M+H] + =291.0699, measured value [M+H] + = 291.0702.

[0851] FTIR (NEET), CM -1 :1592, 1544, 1416, 1383, 1274, 827, 813, 789, 711, 634.

[0852] (Preparation Example 113: N-(pyridazin-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0853] [ka]

[0854] The compound was prepared according to general procedure C using 5-chloro-3-(pyridin-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and pyridazine-3-amine (23 mg, 0.244 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (dichloromethane / methanol, 100:0 to 90:10 gradient). The product was obtained as a pale yellow solid (46 mg, 74% yield).

[0855] 1 H NMR(500MHz,DMSO-d6)δ(ppm)10.42(s,1H), 8.82(dd,J=4.6,1.5Hz,1H), 8.71(d,J=6.0Hz,2H), 8.58(s,1H), 8.44( d,J=8.9Hz,1H), 8.42(dd,J=9.1,1.4Hz,1H), 8.10(dd,J=4.7,1.6Hz,2H), 7.65~7.62(m,1H), 7.60(d,J=8.9Hz,1H).

[0856] 13 C NMR (126MHz, DMSO-d6) δ (ppm) 156.85, 152.41, 150.23, 149.80, 146.09, 141.37, 133.17, 131.95, 131.14, 127.64, 126.56, 122.30, 116.87, 110.41.

[0857] HRMS (APCI): Theoretical value (C 16 H 12 N5S)[M+H] + =306.0808, measured value [M+H] + = 306.0807.

[0858] FTIR (NEET), CM -1 :3593~2799, 1599, 1572, 1440, 1393, 813, 700.

[0859] (Preparation Example 114: 3-(pyridine-4-yl)-N-(pyrimidine-4-yl)thieno[3,2-b]pyridine-5-amine)

[0860] [ka]

[0861] Following general procedure C, the compound was prepared using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) and pyrimidine-4-amine (23 mg, 0.244 mmol), dissolved in DMF (2 mL), instead of dioxane. Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (dichloromethane / methanol, 100:0 to 90:10 gradient). The product was obtained as a pale yellow solid (46 mg, 74% yield).

[0862] 1 H NMR(500MHz,DMSO-d6)δ(ppm)10.44(s,1H), 8.77(s,1H), 8.73(d,J=3.0Hz,2H), 8.62(s,1H), 8.50(d,J=5. 5Hz,1H), 8.49(d,J=8.9Hz,1H), 8.13(dd,J=4.8,1.6Hz,2H), 8.07(d,J=5.9Hz,1H), 7.68(d,J=8.9Hz,1H).

[0863] 13 C NMR(126MHz,DMSO-d6)δ(ppm)158.61, 158.00, 156.59, 151.66, 150.34, 149.86, 141.29, 133.25, 132.03, 131.57, 127.42, 122.31, 110.91, 108.13.

[0864] HRMS (APCI): Theoretical value (C 16 H 12 N5S)[M+H] + =306.0808, measured value [M+H] + = 306.0805.

[0865] FTIR (NEET), CM -1:2923, 2852, 1742, 1622, 1599, 1571, 1514, 1401, 983, 827, 802, 626, 420.

[0866] (Preparation Example 115: 5-(pyrazolo[1,5-a]pyrimidine-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0867] [ka]

[0868] The compound was prepared according to general procedure B using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (55 mg, 0.223 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidine (65 mg, 0.268 mmol). Reaction time: 1.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 100:0 to 90:10 gradient). The product was obtained as a pale yellow solid (67 mg, 92% yield).

[0869] 1 H NMR(500MHz,DMSO-d6)δ(ppm)9.28(dd,J=7.0,1.7Hz,1H), 9.04(s,1H), 8.91(s,1H), 8. 84~8.77(m,3H), 8.66(d,J=8.5Hz,1H), 8.63~8.58(m,3H), 7.22(dd,J=7.0,4.0Hz,1H).

[0870] 13 C NMR(126MHz,DMSO-d6)δ(ppm)152.14, 151.47, 149.11, 148.01, 145.09, 144.24, 1 43.01, 137.01, 133.46, 132.29, 131.11, 130.96, 122.50, 116.81, 109.65, 109.25.

[0871] HRMS (APCI): Theoretical value (C18 H 12 N5S)[M+H] + =330.0808, measured value [M+H] + = 330.0810.

[0872] FTIR (NEET), CM -1 :3400, 3067, 1620, 1574, 1524, 1397, 1360, 1254, 1184, 1063, 825, 796, 777, 639, 577.

[0873] (Preparation Example 116: tert-butyl 2-(((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)oxy)-methyl)morpholine-4-carboxylate)

[0874] [ka]

[0875] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (150 mg, 0.609 mmol) dissolved in toluene (9 mL)), potassium hydroxide (82 mg, 1.46 mmol), tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate (53 mg, 0.244 mmol), and 18-crown-6 (10 mg, 0.06 mmol) were added, and the reaction mixture was refluxed for 16 hours. The reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (2 × 25 mL). The integrated organic extract was dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / ethyl acetate, 60:40 to 40:60 gradient). The product was obtained as a pale yellow solid (156 mg, 60% yield).

[0876] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.70(d,J=6.3Hz,2H), 8.07(d,J=8.9Hz,1H), 8.02~7.97(m,3H), 6.91(d,J=8.7Hz,1H), 4.56~4.42(m,2H), 4.10(br s,1H), 3.97(d,J=11.5Hz,1H), 3.92~3.79(m,2H), 3.61(td,J=11.6,2.8Hz,1H), 3.01(s,1H), 2.89(s,1H), 1.47(s,9H).

[0877] 13 C NMR(126MHz,Chloroform-d)δ(ppm)161.88, 154.77, 150.02, 149.94, 141.84, 133.24 , 133.04, 129.00, 127.82, 122.28, 109.35, 80.20, 77.20, 73.73, 66.67, 66.41, 28.38.

[0878] HRMS (APCI): Theoretical value (C 22 H 26 N3O4S)[M+H] + =428.1639, measured value [M+H] + = 428.1638.

[0879] FTIR (NEET), CM -1 :2974, 2860, 1692, 1598, 1580, 1561, 1415, 1390, 1271, 1168, 1132, 1132, 1057, 730.

[0880] (Preparation Example 117: tert-butyl(S)-2-(((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)oxy)-methyl)morpholine-4-carboxylate)

[0881] [ka]

[0882] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) dissolved in toluene (3 mL)), potassium hydroxide (23 mg, 0.406 mmol), tert-butyl(S)-2-(hydroxymethyl)-morpholine-4-carboxylate (53 mg, 0.244 mmol), and 18-crown-6 (5 μL, 0.006 mmol) were added, and the reaction mixture was refluxed for 5 hours. The reaction mixture was quenched to pH 7 with 1 M HCl and extracted with ELISA (2 × 20 mL). The integrated organic extract was dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 0:100 gradient) and TLC for preparation (cyclohexane / siRNA, 80:20). The product was obtained as a pale yellow waxy substance (22 mg, 33%).

[0883] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.72(s,2H), 8.07(d,J=8.9Hz,1H), 8.00(d,J=6.4Hz,3H), 6.91(d,J=8.9Hz,1H), 4.53~4.40(m,2H), 4.12(br s,1H), 3.98(d,J=10.8Hz,1H), 3.89(dd,J=5.3,2.6Hz,2H), 3.61(td,J=11.7,2.8Hz,1H), 3.02(s,1H), 2.89(s,1H), 1.47(s,9H).

[0884] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.89, 149.37, 149.12, 145.69, 144.20, 137.78, 13 5.30, 131.05, 130.78, 129.05, 126.92, 125.44, 124.28, 115.34, 108.10, 105.54, 39.24.

[0885] HRMS (APCI): Theoretical value (C 22 H 26 N3O4S)[M+H]+ =428.1639, measured value [M+H] + = 428.1640.

[0886] FTIR (NEET), CM -1 :3417, 2926, 1692, 1599, 1416, 1391, 1271, 1271, 1168, 1132, 813.

[0887] (Preparation Example 118: 2-(((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)oxy)methyl)morpholine)

[0888] [ka]

[0889] Trifluoroacetic acid (1 mL) was added dropwise to a solution (tert-butyl 2-(((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)oxy)-methyl)morpholine-4-carboxylate (Preparation Example 116) (125 mg, 0.292 mmol) dissolved in dichloromethane (2.5 mL)). The reaction mixture was stirred at 25°C for 45 minutes. The residue was purified by flash chromatography (dichloromethane / methanol, gradient from 100:0 to 85:5). The reaction mixture was extracted in toluene (10 mL) and washed with saturated aqueous NaHCO3 (2 × 15 mL). The integrated organic extract was dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The product was obtained as a pale yellow solid (84 mg, 88%).

[0890] 1H NMR(500MHz,Methanol-d4)δ(ppm)8.61(dd,J=4.7,1.8Hz,2H), 8.43(s,1H), 8.26(d,J=8.9Hz,1H), 8.24(dd,J=4.7,1.7Hz,2H), 6.92(d,J=8.9Hz,1H), 4.48 (t,J=5.0Hz,2H), 4.07~4.03(m,1H), 4.02~3.96(m,1H), 3.77~3.64(m,1H), 3. 17(dd,J=12.7,2.4Hz,1H), 3.01~2.94(m,2H), 2.89(dd,J=12.6,10.8Hz,1H).

[0891] 13 C NMR(126MHz,Methanol-d4)δ(ppm)163.32, 151.27, 150.20, 144.36, 135.04, 133.22, 132.08, 129.45, 123.87, 110.12, 74.98, 67.72, 67.32, 47.73, 45.52.

[0892] HRMS (APCI): Theoretical value (C 17 H 18 N3O2S)[M+H] + =328.1114, measured value [M+H] + = 328.1111.

[0893] FTIR (NEET), CM -1 :3600~3142, 2924, 2854, 1633~2364, 1674, 1602, 1448, 1270, 1201, 1129, 830, 784, 642.

[0894] (Preparation Example 119: 3-(isothiazol-5-yl)-5-(1-methyl-1H-pyrazole-3-yl)thieno[3,2-b]pyridine)

[0895] [ka]

[0896] The compound was prepared according to general procedure B using 5-chloro-3-(isothiazol-5-yl)thieno[3,2-b]pyridine (Preparation Example 66) (45 mg, 0.178 mmol) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (44 mg, 0.214 mmol). Reaction time: 45 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a white solid (26 mg, 49% yield).

[0897] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.53(d,J=2.0Hz,1H), 8.22(d,J=8.4Hz,1H), 8.12(d,J=8.5Hz, 1H), 8.09(s,1H), 7.77(d,J=1.8Hz,1H), 7.49(d,J=2.3Hz,1H), 7.27(d,J=2.3Hz,1H), 4.02(s,3H).

[0898] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 157.60, 155.81, 151.88, 151.71, 150.58, 131.81, 131.67, 131.20, 128.25, 126.34, 119.42, 116.27, 105.67, 39.28.

[0899] HRMS (APCI): Theoretical value (C 14 H 11 N4S2)[M+H] + =299.0420, measured value [M+H] + =299.0423.

[0900] FTIR (NEET), CM -1 :3099, 1570, 1558, 1422, 1282, 1225, 829, 814, 778, 768, 548, 438, 434.

[0901] (Preparation Example 120: 3-((3-(isothiazol-5-yl)thieno[3,2-b]pyridine-5-yl)amino)-1-methyl-1H-pyrazole-4-carbonitrile)

[0902] [ka]

[0903] The compound was prepared according to general procedure C using 5-chloro-3-(isothiazol-5-yl)thieno[3,2-b]pyridine (Preparation Example 66) (45 mg, 0.178 mmol) and 1,4-dimethyl-1H-pyrazole-3-amine (26 mg, 0.214 mmol). After 30 hours, BrettPhosPdG3 (10 mg, 0.011 mmol) and methanol (1 mL) were added, and the mixture was refluxed for a further 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 0:100 gradient). The product was obtained as a white solid (5 mg, 10% yield).

[0904] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.44(d,J=1.9Hz,1H), 8.39(s,1H), 8.22(s,1H) , 8.17(d,J=8.9Hz,1H), 7.90(d,J=2.0Hz,1H), 7.20(d,J=8.8Hz,1H), 3.95(s,3H).

[0905] 13 C NMR(126MHz,Methanol-d4)δ(ppm)159.51, 156.95, 155.58, 152.53, 151.60, 13 8.06, 133.74, 128.65, 128.10, 126.73, 120.66, 114.42, 109.96, 87.05, 39.78.

[0906] HRMS (APCI): Theoretical value (C 15 H 11 N6S2)[M+H] + =339.0481, measured value [M+H]+ =339.0478.

[0907] FTIR (NEET), CM -1 :3089, 2224, 1581, 1552, 1533, 1400, 1349, 1163, 799.

[0908] (Preparation Example 121: 3-phenyl-5-(1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[0909] [ka]

[0910] The compound was prepared according to general procedure B using 5-chloro-3-phenylthieno[3,2-b]pyridine (Preparation Example 1) (63 mg, 0.259 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (96 mg, 0.324 mmol). The reaction was stirred at 110°C for 2 hours, then at 25°C for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 50:50 gradient) and preparation TLC (dichloromethane / methanol, 98:2). The product was obtained as a white solid (27 mg, 37% yield).

[0911] 1 H NMR(500MHz,Methanol-d4)δ(ppm)8.32(d,J=8.4Hz,1H), 8.23(s,2H), 8.12(d,J=7.7Hz ,2H), 8.06(s,1H), 7.69(d,J=8.4Hz,1H), 7.49(t,J=7.6Hz,2H), 7.38(t,J=7.4Hz,1H).

[0912] 13C NMR (126MHz, Methanol-d4) δ (ppm) 154.22, 150.96, 137.64, 136.13, 133.35, 132.80, 129.56, 129.38, 128.83, 128.58, 116.95.

[0913] HRMS: Theoretical value (C 16 H 11 N3S)[M+H] + =278.0746, measured value [M+H] + =278.0744.

[0914] FTIR (NEET), CM -1 :3136,1583,1566,1397,1381,1254,1214,1125,1027,987,864,811,743,717,687,614,544,489.

[0915] (Preparation Example 122: 3-phenyl-5-(3,4,5-trifluorophenyl)thieno[3,2-b]pyridine)

[0916] [ka]

[0917] The compound was prepared according to general procedure B using 5-chloro-3-phenylthieno[3,2-b]pyridine (Preparation Example 1) (81 mg, 0.330 mmol) and (3,4,5-trifluorophenyl)boronic acid (70 mg, 0.396 mmol). Reaction temperature: 80°C. Reaction time: 19 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / RINKAN, 100:0 to 95:5 gradient). The product was obtained as a white solid (60 mg, 54% yield).

[0918] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.29(d,J=8.5Hz,1H), 8.06(d,J=6.8Hz,1H), 7.90(s,1H), 7 .79(dd,J=8.8,6.6Hz,2H), 7.68(d,J=8.5Hz,1H), 7.55(t,J=7.5Hz,2H), 7.45(d,J=7.5Hz,1H).

[0919] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.34, 152.51(dd,J=10.1,4.17Hz), 151.22(q,J=2.4Hz), 150.54(dd,J=10.1,4.0Hz), 141.32(t,J=15.6Hz), 139.30(t,J=15.6Hz), 137.15, 135.67~135.52(m), 134.29, 133.73, 131. 68, 128.56, 128.54, 127.95, 127.89, 115.26, 110.99 (dd, J=17.5, 5.4Hz).

[0920] 19 F NMR (471MHz, Chloroform-d) δ -133.95 (d, J=20.5Hz), -160.18 (t, J=20.4Hz).

[0921] HRMS: theoretical value (C 19 H 11 F3NS)[M+H + =342.0559, measured value [M+H] + =342.0557.

[0922] FTIR(ニート)、cm -1 :1619, 1551, 1520, 1452, 1444, 1412, 1390, 1353, 1240, 1207, 1172, 1037, 973, 865, 778, 750, 733, 692, 644, 585, 441.

[0923] (Preparation example 123: 5-(フルラン-3-イル)-3-フェニルチエノ[3,2-b]ピリジン)

[0924] [ka]

[0925] The compound was prepared according to general procedure B using 5-chloro-3-phenylthieno[3,2-b]pyridine (Preparation Example 1) (75 mg, 0.305 mmol) and 2-(flulan-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (71 mg, 0.366 mmol). Reaction temperature: 80°C. Reaction time: 20 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 98:2 gradient). The product was obtained as a brown solid (77 mg, 92% yield).

[0926] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.18 (d, J=8.4Hz, 1H), 8.15~8.07 (m, 3H), 7.85 (s, 1H) ), 7.53~7.50(m,3H), 7.49(d,J=4.0Hz,1H), 7.40(t,J=7.4Hz,1H), 7.03(d,J=1.1Hz,1H).

[0927] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.23, 149.20, 143.74, 141.35, 136.79, 13 4.60, 132.23, 131.07, 128.54, 128.37, 127.62, 127.00, 124.30, 115.83, 109.09.

[0928] HRMS: Theoretical value (C 17 H 12 NOS)[M+H] + =278.0634, measured value [M+H] + = 278.0637.

[0929] FTIR (NEET), CM -1 :1596, 1564, 1550, 1504, 1390, 1157, 1063, 872, 791, 777, 750, 719, 692, 555.

[0930] (Preparation Example 124: 4-(3-phenylthieno[3,2-b]pyridine-5-yl)isoxazole)

[0931] [ka]

[0932] The compound was prepared according to general procedure B using 5-chloro-3-phenylthieno[3,2-b]pyridine (Preparation Example 1) (80 mg, 0.330 mmol) and 4-isoxazoleboronic acid pinacol ester (77 mg, 0.396 mmol). Reaction temperature: 80°C. After 3 hours, triethylamine (0.15 mL, 0.990 mmol) was added, and the mixture was refluxed for a further 18 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / RINKAN, 100:0 to 98:2 gradient). The product was obtained as a yellow solid (18 mg, 30% yield).

[0933] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.94(d,J=2.3Hz,1H), 8.27(d,J=9.0Hz,1H ), 7.84(s,1H), 7.68~7.57(m,5H), 7.52(t,J=7.2Hz,1H), 7.39(d,J=9.0Hz,1H).

[0934] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 181.22, 153.03, 141.21, 135.36, 133.23, 131.86, 130.09, 129.61, 129.31, 129.19, 127.99, 119.64, 115.77, 80.93.

[0935] HRMS: Theoretical value (C 16 H 11 N2O S )[M+H] + =279.0587, measured value [M+H] + =279.0588.

[0936] FTIR (NEET), CM -1 :3127, 2957, 2921, 2192, 1731, 1598, 1511, 1496, 1424, 1378, 1319, 1249, 1233, 1155, 960, 900, 860, 814, 795, 757, 738, 695, 652, 640, 594, 558, 486, 448, 421.

[0937] (Preparation Example 125: 4-(5-chlorothieno[3,2-b]pyridine-3-yl)-N,N-dimethylpyridine-2-amine)

[0938] [ka]

[0939] The compound was prepared according to general procedure B using 4-(5-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)morpholine (Preparation Example 41) (45 mg, 0.136 mmol) and 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (48 mg, 0.170 mmol). After 4 hours, triethylamine was added and the mixture was refluxed for a further 16 hours. The solvent was evaporated and the residue was purified by two flash chromatography cycles (cyclohexane / siRNA, 80:20 to 60:40 gradient). The product was obtained as a white solid (41 mg, 67% yield).

[0940] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.90(s,1H), 8.30(dd,J=8.8,2.4Hz,1H), 8.14(d,J=8.4Hz,1H), 8.11(s,1H), 8.04(br s,1H), 7.73(s,1H), 7.47(s,1H), 7.41~7.31(m,3H), 7.29~7.27(m,2H), 6.77(d,J=8.8Hz,1H), 5.39(s,2H), 3.88(s,4H), 3.60(s,4H).

[0941] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 153.21, 149.49, 147.11, 138.22, 137.75, 136.39, 131.54, 131. 14, 128.85, 128.54, 128.10, 127.69, 125.00, 124.27, 121.10, 115.58, 106.55, 66.76, 56.28, 45.85.

[0942] HRMS (APCI): Theoretical value (C 26 H 24 N5OS)[M+H] + =454.1696, measured value [M+H] + = 454.1693.

[0943] FTIR (NEET), CM -1 :3060, 2960, 2857, 1602, 1577, 1556, 1481, 1450, 1402, 1365, 1317, 1243, 1215, 1182, 1173, 1114, 991, 942, 796, 702, 628, 578, 470.

[0944] (Preparation Example 126: Ethyl 3-((3-(2-((tert-butoxycarbonyl)amino)pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)amino)-1-methyl-1H-pyrazole-4-carboxylate)

[0945] [ka]

[0946] The compound was prepared according to general procedure C using tert-butyl(4-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)carbamate (Preparation Example 23) (100 mg, 0.276 mmol) and ethyl 3-amino-1-methyl-1H-pyrazole-4-carboxylate (56 mg, 0.331 mmol). Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, gradient from 70:30:0 to 0:95:5). The product was obtained as a white solid (77 mg, yield 73%).

[0947] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.85(s,1H), 8.46(m,1H), 8.35(dd,J=5.2,0.8Hz,1H), 8.18(d,J=8.9Hz,1H), 8.13(d,J=3.1Hz,1H) , 8.12(d,J=4.3Hz,1H), 8.08(s,1H), 7.72(s,1H), 7.46(s,1H), 4.33(q,J=7.1Hz,2H), 3.88(s,3H), 1.56(s,9H), 1.39(t,J=7.1Hz,3H).

[0948] 13 C NMR(126MHz,Chloroform-d)δ(ppm)163.81, 152.42, 152.15, 151.99, 151.60, 151.54, 148.00, 144.12, 133 .11, 132.86, 132.39, 129.64, 126.77, 118.13, 110.42, 108.60, 100.08, 80.81, 60.08, 39.42, 28.34, 14.38.

[0949] HRMS (APCI): Theoretical value (C 24 H 27 N6O4S)[M+H] + =495.1809, measured value [M+H] + = 495.1805.

[0950] FTIR (NEET), CM -1:2977, 1717, 1689, 1566, 1391, 1287, 1156, 1057, 773.

[0951] (Preparation Example 127: Methyl 3-((3-(2-(((tert-butoxycarbonyl)amino)methyl)pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)amino)-1-methyl-1H-pyrazole-4-carboxylate (intermediate))

[0952] [ka]

[0953] The compound was prepared according to general procedure C using tert-butyl((4-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)methyl)carbamate (Preparation Example 26) (427 mg, 1.13 mmol) and ethyl 3-amino-1-methyl-1H-pyrazole-4-carboxylate (229 mg, 1.36 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 0:100 gradient). The product was obtained as an impure pale yellow solid (64 mg, yield less than 55%). The product was used in the next step without further purification.

[0954] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.80(s,1H), 8.64(d,J=5.2Hz,1H), 8.16(d,J=8.9Hz,1H), 8.13(s,1H), 7.97(s,1H), 7.92~7.90(m,1) H), 7.70(s,1H), 7.54(s,1H), 5.69(s,1H), 4.54(d,J=5.0Hz,2H), 4.26(q,J=7.1Hz,2H), 3.69(s,3H), 1.46(s,9H), 1.32(t,J=7.1Hz,3H).

[0955] 13C NMR(126MHz,Chloroform-d)δ(ppm)164.27, 156.46, 151.99, 151.56, 151.40, 149.39, 142.61, 133.13, 132.84 , 132.77, 132.43, 129.21, 126.79, 121.30, 120.26, 108.82, 99.74, 79.29, 59.65, 51.28, 39.45, 28.42, 14.45.

[0956] HRMS (APCI): Theoretical value (C 25 H 29 N6O4S)[M+H] + = 509.1966 (product A), measured value [M+H] + = 495.1809 (Measurement in MeOH, product B was detected as the only product).

[0957] FTIR (NEET), CM -1 :3360, 2978, 1688, 1568, 1553, 1511, 1391, 1246, 1165, 1109, 775, 730, 647.

[0958] (Preparation Example 128: Methyl 3-((3-(2-(aminomethyl)pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)amino)-1-methyl-1H-pyrazole-4-carboxylate)

[0959] [ka]

[0960] According to the general procedure D, a compound was prepared using ethyl 3-((3-(2-((tert-butoxycarbonyl)amino)pyridin-4-yl)thieno[3,2-b]pyridin-5-yl)amino)-1-methyl-1H-pyrazole-4-carboxylate (Preparation Example 128) (251 mg, 0.495 mmol). Reaction time: 16 hours. The solvent was evaporated and the residue was purified by preparative TLC (dichloromethane / methanol / 7M NH3 in methanol, 92:5:3, eluted once; then EtOAc, eluted three times). The product was obtained as a pale yellow solid (95 mg, yield 47%).

[0961] 1 H NMR (500 MHz, Methanol-d4) δ (ppm) 8.71 (d, J = 5.1 Hz, 1H), 8.42 (s, 1H), 8.34 (s, 1H), 8.30 (d, J = 9.0 Hz, 1H), 8.25 - 8.21 (m, 2H), 8.02 (s, 1H), 4.39 (s, 2H), 3.89 (s, 3H), 3.86 (s, 3H).

[0962] 13 C NMR (126 MHz, Methanol-d4) δ (ppm) 166.31, 153.76, 153.57, 152.69, 152.48, 150.66, 144.86, 134.88, 134.04, 132.65, 132.37, 128.42, 123.36, 121.90, 109.93, 100.50, 51.74, 44.46, 39.56.

[0963] HRMS (APCI): Theoretical value (C 19 H 19 N6O2S2) [M + H] + = 395.1285, Measured value [M + H] + = 395.1282.

[0964] FTIR (neat), cm -1 : 3404, 3368, 1688, 1604, 1580, 1391, 1299, 1124, 774.

[0965] (Preparation Example 129: 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-(1-methyl-1H-pyrazole-3-yl)thieno[3,2-b]pyridine)

[0966] [ka]

[0967] Following general procedure B, the compounds were prepared using 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (Preparation Example 52) (50 mg, 0.174 mmol) and 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (44 mg, 0.214 mmol). After 6 hours, additional potassium phosphate (55 mg, 0.261 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13 mg, 0.018 mmol), and H2O (0.2 mL) were added, and the mixture was refluxed for a further 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 80:20 to 0:100 gradient) and TLC for preparation (dichloromethane / methanol, 97:3). The product was obtained as a brown solid (10 mg, 17% yield).

[0968] 1 H NMR(500MHz,Chloroform-d)δ(ppm)10.19(s,1H), 8.53(s,1H), 8.31(d,J=9.1Hz,1H), 8.29(d,J=8.5Hz,1H) ), 8.15(d,J=8.6Hz,1H), 8.07(d,J=8.0Hz,2H), 7.47(d,J=2.2Hz,1H), 7.06(d,J=2.3Hz,1H), 4.03(s,3H).

[0969] 1313C NMR (126 MHz, Chloroform-d) δ (ppm) 157.74, 153.16, 152.10, 151.85, 150.47, 132.89, 131.86, 131.41, 131.05, 130.74, 127.99, 127.72, 122.41, 116.29, 115.79, 105.07, 39.29.

[0970] HRMS (APCI): Calculated for (C 17 H 13 N6S) [M + H] + = 333.0917, Found [M + H] + = 333.0921.

[0971] (Preparation Example 130: 3-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5-(pyrimidin-2-yl)thieno[3,2-b]pyridine)

[0972]

Chem.

[0973] Solution (dissolved 3-([1,2,4]Triazolo[1,5-a]pyridin-6-yl)-5-chlorothieno[3,2-b] (Preparation Example 52) (50 mg, 0.174 mmol) in dioxane (3 mL)), added 2-(tributylstannyl)pyrimidine (73 μL, 0.226 mmol) and bis(tri-tert-butylphosphine)palladium(0) (7 mg, 0.014 mmol), and refluxed the reaction mixture for 16 h. Evaporated the solvent and purified the residue by flash chromatography (cyclohexane / EtOAc / methanol, gradient of 50:50:0 to 0:95:5). Obtained the product as a white solid (18 mg, 32%).

[0974] 1H NMR(500MHz,DMSO-d6)δ(ppm)10.50(s,1H), 9.08(d,J=4.9Hz,2H), 8.86(s,1H), 8.80(d,J=8.5Hz,1H), 8.5 7(s,1H), 8.53(d,J=8.5Hz,1H), 8.46(dd,J=9.3,1.7Hz,1H), 8.01(d,J=9.3Hz,1H), 7.63(d,J=4.8Hz,1H).

[0975] 13 C NMR(126MHz,DMSO-d6)δ(ppm)163.12, 158.05, 154.37, 152.42, 152.40, 149.06, 1 35.04, 132.70, 130.98, 130.21, 129.72, 127.29, 121.18, 121.09, 118.96, 115.92.

[0976] HRMS (APCI): Theoretical value (C 17 H 11 N6S)[M+H] + =330.0808, measured value [M+H] + =331.0708.

[0977] FTIR (NEET), CM -1 :1638, 1555, 1439, 1421, 1407, 1256, 907, 793, 715, 656, 634, 586, 447.

[0978] (Preparation Example 131: 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-(pyridine-3-yl)thieno[3,2-b]pyridine)

[0979] [ka]

[0980] The compound was prepared using 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (Preparation Example 52) (50 mg, 0.174 mmol) and pyridine-3-ylboronic acid (26 mg, 0.209 mmol) according to general procedure B. Reaction time: 1 hour. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 100:0 to 95:5 gradient). The product was obtained as a white solid (24 mg, 42%).

[0981] 1 H NMR(500MHz,Methanol-d4)δ(ppm)10.09(s,1H), 9.37(d,J=2.3Hz,1H), 8.67(dt,J=7.9,2.0Hz,1H), 8.64(dd,J=4.8,1.6Hz,1H), 8.58(d,J=8.5 Hz,1H), 8.53(s,1H), 8.48(s,1H), 8.41(dd,J=9.3,1.7Hz,1H), 8.07(d,J=8.5Hz,1H), 7.91(dd,J=9.2,0.9Hz,1H), 7.63(dd,J=8.0,4.8Hz,1H).

[0982] 13 C NMR(126MHz,Methanol-d4)δ(ppm)154.83, 154.12, 153.41, 150.64, 150.38, 148.91, 136.80 , 136.66, 135.49, 133.78, 132.72, 131.74, 131.61, 128.78, 125.58, 123.82, 117.82, 116.57.

[0983] HRMS (APCI): Theoretical value (C 18 H 12 N5S)[M+H] + =330.0808, measured value [M+H] + =330.0811.

[0984] FTIR (NEET), CM -1 :3072, 1637, 1579, 1391, 1261, 1190, 811, 789, 699, 657, 574, 423.

[0985] (Preparation example 132: 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-(pyridine-4-yl)thieno[3,2-b]pyridine)

[0986] [ka]

[0987] Following general procedure B, the compound was prepared using 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (Preparation Example 52) (41 mg, 0.139 mmol) and pyridine-4-ylboronic acid (21 mg, 0.167 mmol). After 2 hours, additional potassium phosphate (88 mg, 0.417 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (5 mg, 0.007 mmol) were added, and the mixture was refluxed for a further 30 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, gradient of 50:50:0 to 0:97:3). The product was obtained as a white solid (25 mg, 54%).

[0988] 1 H NMR(500MHz,DMSO-d6)δ(ppm)10.08(s,1H), 8.80(t,J=4.3Hz,2H), 8.79(d,J=6.0Hz,2H), 8.59(s,1H) ), 8.44(dd,J=9.2,1.8Hz,1H), 8.25(s,1H), 8.19(dd,J=4.5,1.6Hz,2H), 8.03(dd,J=9.3,0.9Hz,1H).

[0989] 13 C NMR(126MHz,DMSO-d6)δ(ppm)154.42, 152.40, 151.55, 150.47, 149.10, 145.63, 1 34.30, 133.24, 131.38, 130.60, 129.98, 127.17, 121.21, 121.02, 116.96, 115.91.

[0990] HRMS (APCI): Theoretical value (C 18 H 12 N5S)[M+H] + =330.0808, measured value [M+H] + =330.0811.

[0991] FTIR (NEET), CM -1 :3094, 3060, 2955, 2923, 2853, 1719, 1598, 1549, 1437, 1393, 1315, 1264, 1239, 1183, 1167, 1124, 809, 726, 693, 658, 538.

[0992] (Preparation Example 133: tert-butyl 4-((3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)thieno[3,2-b]pyridine-5-yl)amino)-1H-pyrazole-1-carboxylate)

[0993] [ka]

[0994] To a solution (3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (Preparation Example 52) (60 mg, 0.209 mmol) dissolved in dioxane (2 mL)), triethylamine (87 μL, 0.627 mmol), tert-butyl 4-amino-1H-pyrazole-1-carboxylate (46 mg, 0.251 mmol), and BrettPhosPdG3 (9 mg, 0.016 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 30:70 to 0:100 gradient). The product was obtained as a brown solid (30 mg, 33%).

[0995] 1H NMR(500MHz,Chloroform-d)δ(ppm)9.47(s,1H), 8.44(s,1H), 8.37(s,1H), 8.16(d,J=9.2Hz,1H), 8.02(d,J= 8.7Hz,1H), 7.91(d,J=9.3Hz,1H), 7.85(s,1H), 7.76(s,1H), 6.78(d,J=8.9Hz,1H), 6.57(s,1H), 1.58(s,9H).

[0996] 13 C NMR(126MHz,Chloroform-d)δ(ppm)154.17, 153.60, 151.33, 147.64, 137.93, 132.43, 130.81, 1 30.57, 127.54, 127.07, 125.66, 125.46, 122.37, 120.49, 119.86, 116.38, 107.53, 85.26, 27.88.

[0997] HRMS (APCI): Theoretical value (C 21 H 20 N7O2S)[M+H] + =434.1394, measured value [M+H] + = 434.1392.

[0998] FTIR (NEET), CM -1 :3295, 3095, 2981, 1746, 1580, 1419, 1381, 1371, 1249, 1149, 955, 843, 731, 660.

[0999] (Preparation Example 134: 3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)-N-(1H-pyrazole-4-yl)thieno[3,2-b]pyridine-5-amine)

[1000] [ka]

[1001] To a solution (1 mL of dichloromethane in which tert-butyl 4-((3-([1,2,4]triazolo[1,5-a]pyridine-6-yl)thieno[3,2-b]pyridine-5-yl)amino)-1H-pyrazole-1-carboxylate (Preparation Example 133) (19 mg, 0.044 mmol) was dissolved), trifluoroacetic acid (0.3 mL) was added, and the reaction mixture was stirred at 25°C for 2 hours. The solvent was evaporated, and the residue was purified by TLC (7 M NH3 in cyclohexane / siRNA / methanol, 10:88:2). The product was obtained as a white solid (4 mg, 27%).

[1002] 1 H NMR(500MHz,Chloroform-d)δ(ppm)9.78(s,1H), 8.46(s,1H), 8.33(d,J=9.0Hz,1H), 8.15 (s,1H), 8.03(d,J=9.0Hz,1H), 7.87(d,J=9.3Hz,2H), 7.73(s,1H), 6.81(d,J=8.9Hz,1H).

[1003] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 156.00, 154.73, 152.34, 133.15, 132.89, 131.20, 128.76, 128.51, 125.47, 124.75, 116.23, 109.82.

[1004] HRMS (APCI): Theoretical value (C 16 H 12 N7S)[M+H] + =334.0869, measured value [M+H] + =334.0865.

[1005] FTIR (NEET), CM -1 :2923, 2853, 2363, 2237, 2182, 2168, 2114, 1990, 1579, 1396, 426.

[1006] (Preparation Example 135: 3-([1,2,4]triazolo[4,3-a]pyridine-6-yl)-N-(1-methyl-1H-pyrazole-3-yl)thieno[3,2-b]pyridine-5-amine)

[1007] [ka]

[1008] The compound was prepared according to general procedure B using 3-([1,2,4]triazolo[4,3-a]pyridine-6-yl)-5-chlorothieno[3,2-b]pyridine (Preparation Example 58) (55 mg, 0.192 mmol) and 1-methyl-1H-pyrazole-3-amine (20 μL, 0.230 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:95:5 gradient). The product was obtained as a white solid (27 mg, 40%).

[1009] 1 H NMR(500MHz,Methanol-d4)δ(ppm)9.82(s,1H), 8.23(s,1H), 8.11(dd,J=9.2,1.8Hz,2H), 7.82(d ,J=9.6Hz,1H), 7.53(d,J=2.2Hz,1H), 7.16(d,J=8.9Hz,1H), 6.51(d,J=2.3Hz,1H), 3.84(s,3H).

[1010] 13 C NMR(126MHz,Methanol-d4)δ(ppm)155.49, 151.02, 149.75, 144.57, 138.05, 133.36, 13 2.57, 131.83, 130.59, 129.19, 126.45, 124.00, 123.87, 115.19, 109.50, 97.87, 38.73.

[1011] HRMS (APCI): Theoretical value (C 17 H 14 N7S)[M+H] +=348.1026, measured value [M+H] + = 348.1024.

[1012] FTIR (NEET), CM -1 :2923, 2853, 1709, 1583, 1545, 1437, 1411, 1165, 724, 699, 567, 533.

[1013] (Preparation Example 136: 5-chloro-3-(1-phenylvinyl)thieno[3,2-b]pyridine (intermediate))

[1014] [ka]

[1015] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.804 mmol) and (1-phenylvinyl)boronic acid (143 mg, 0.965 mmol) according to general procedure A. Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30-40:60 gradient) and preparation TLC (cyclohexane / siRNA, 90:10, single elution, 100:0, single elution). The product was obtained as an impure yellow waxy substance (150 mg, yield less than 69%). This product was used in the next step without further purification.

[1016] 1 H NMR (500MHz, Chloroform-d) (Main product) δ(ppm)8.09(d, J=8.5Hz, 1H), 7.48(s, 1H), 7.42(d, J=1.4Hz, 1H), 7.39(d, J=1.5Hz, 1H), 7.36~7.34(m,3H), 7.29(d,J=8.5Hz,1H), 6.50(d,J=1.5Hz,1H), 5.74(d,J=1.5Hz,1H).

[1017] HRMS (APCI): Theoretical value (C 15 H 11 ClNS) (main product) [M+H]+ =272.0295, measured value [M+H] + = 272.0298.

[1018] (Preparation Example 137: 5-(1-methyl-1H-pyrazole-4-yl)-3-(1-phenylvinyl)thieno[3,2-b]pyridine, and 3-(1-methyl-1H-pyrazole-4-yl)-5-(1-phenylvinyl)thieno[3,2-b]pyridine)

[1019] [ka]

[1020] The compounds were prepared according to general procedure B using (5-chlorothieno[3,2-b]pyridine-3-yl)(phenyl)methanone (Preparation Example 136) (144 mg, 0.371 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (93 mg, 0.445 mmol). Reaction time: 1 hour. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 98:2 to 97:3 gradient). The product was obtained as a yellow solid (Sample A) (29 mg, 25%) and a yellow waxy substance (Sample B) (19 mg).

[1021] 1 H NMR (500MHz, Chloroform-d) (Sample A) δ (ppm) 8.17 (s, 1H), 8.13 (d, J=8.5Hz, 1H), 7.96 (s, 1H), 7.69 (s, 1H), 7.48~7.44(m,3H), 7.44~7.38(m,3H), 6.14(d,J=1.2Hz,1H), 5.69(d,J=1.2Hz,1H), 3.84(s,3H).

[1022] 1H NMR (500MHz, Chloroform-d) (Sample B) δ (ppm) 8.11 (d, J = 8.4 Hz, 1H), 7.92 (s, 1H), 7.81 (s, 1H), 7.49 (s, 1H), 7.47~7.41(m,3H), 7.40~7.31(m,3H), 6.59(d,J=1.9Hz,1H), 5.70(d,J=1.9Hz,1H), 3.94(s,3H).

[1023] 13 C NMR (126MHz, Chloroform-d) (Sample A) δ (ppm) 155.66, 152.72, 149.69, 141.18, 137.2 3, 132.47, 130.64, 129.03, 128.04, 127.48, 122.37, 117.60, 117.47, 115.77, 38.86.

[1024] 13 C NMR (126MHz, Chloroform-d) (Sample B) δ (ppm) 153.74, 149.30, 142.97, 142.43, 137.71, 136.3 9, 131.33, 130.98, 129.72, 129.04, 128.22, 128.09, 127.41, 124.14, 117.07, 115.25, 39.11.

[1025] HRMS (APCI) (Sample A): Theoretical value (C 19 H 16 N3S)[M+H] + =318.1059, measured value [M+H] + = 318.1061.

[1026] HRMS (APCI) (Sample B): Theoretical value (C 19 H 16 N3S)[M+H] + =318.1059, measured value [M+H] + = 318.1059.

[1027] FTIR (NEET), CM -1 (Sample A): 3094, 2933, 1563, 1539, 1402, 1375, 1174, 982, 777, 702.

[1028] FTIR (neat), cm -1 (Sample B): 3097, 2937, 1578, 1539, 1490, 1399, 1214, 979, 830, 805, 777, 701, 656.

[1029] (Preparation Example 138: 3-Bromo-5-phenoxythieno[3,2-b]pyridine (intermediate))

[1030]

Chemical formula

[1031] Solution (dissolved 3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.805 mmol) in DMF (8 mL)), added phenol (76 mg, 0.805 mmol), copper(I) cyanide (4 mg, 0.040 mmol), cesium carbonate (367 mg, 1.13 mmol), and N,N-dimethylethylenediamine (10 μL, 0.089 mmol), and refluxed the reaction mixture for 16 hours. Evaporated the solvent and purified the residue twice by flash chromatography (cyclohexane / EtOAc, gradient of 97:3 to 99:1). Obtained the product as a pale yellow solid (68 mg, 22%). The product was used in the next step without further purification.

[1032] 1 H NMR (500 MHz, Chloroform-d) δ (ppm) 7.99 (d, J = 8.7 Hz, 1H), 7.61 (s, 1H), 7.34 - 7.27 (m, 2H), 7.17 - 7.14 (m, 2H), 7.13 - 7.08 (m, 1H), 6.81 (d, J = 8.7 Hz, 1H).

[1033] 13 C NMR (126 MHz, Chloroform-d) δ (ppm) 162.59, 154.23, 150.24, 133.88, 129.57, 128.84, 127.70, 126.83, 124.64, 120.92, 109.31.

[1034] HRMS (APCI): Theoretical value (C 13 H9ClNOS)[M+H] + =262.0088, measured value [M+H] + = Not detected.

[1035] FTIR (NEET), CM -1 :3102, 1572, 1546, 1483, 1390, 1281, 1235, 894, 811, 767, 693.

[1036] (Preparation Example 139: 3-(1-methyl-1H-pyrazole-4-yl)-5-phenoxythieno[3,2-b]pyridine)

[1037] [ka]

[1038] To a solution (3-bromo-5-phenoxythieno[3,2-b]pyridine (45 mg, 0.206 mmol) (Preparation Example 138) dissolved in dioxane (3 mL)), tripotassium phosphate (131 mg, 0.618 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (52 mg, 0.248 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (12 mg, 0.016 mmol), and H2O (0.5 mL) were added, and the reaction mixture was refluxed for 4 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (cyclohexane / siRNA, 60:40 to 40:60 gradient). The product was obtained as a pale yellow waxy substance (22 mg, 35%).

[1039] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.13(d,J=8.7Hz,1H), 7.82(d,J=7.7Hz,2H), 7.64(s,1H) , 7.52~7.46(m,2H), 7.33~7.29(m,1H), 7.28~7.26(m,2H), 7.03(d,J=8.7Hz,1H), 3.76(s,3H).

[1040] 13 C NMR(126MHz,Chloroform-d)δ(ppm)162.31, 154.29, 150.45, 136.83, 133.67, 12 9.52, 128.81, 128.04, 127.98, 124.68, 122.50, 122.33, 115.60, 108.21, 38.71.

[1041] HRMS (APCI): Theoretical value (C 17 H 14 N3OS)[M+H] + 308.0852, measured value [M+H] + =308.0854.

[1042] FTIR (NEET), CM -1 :1574, 1549, 1488, 1398, 1375, 1277, 1237, 1199, 1158, 982, 811, 772, 692.

[1043] (Preparation Example 140: 5-chloro-2-iodo-3-(pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[1044] [ka]

[1045] To a degassed solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (200 mg, 0.812 mmol) dissolved in carbon tetrachloride (96 μL)), iodine (62 mg, 0.243 mmol), NaIO4 (86 mg, 0.406 mmol), acetic acid (1.2 mL), sulfuric acid (0.4 mL), and H2O (0.1 mL) were added, and the mixture was stirred at 65°C for 8 hours. The reaction mixture was quenched with saturated Na2S2O3 (20 mL), extracted with ethyl acetate (2 × 20 mL), and washed with H2O (20 mL). The integrated organic extract was dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The residue obtained after work-up was purified by flash chromatography (cyclohexane / ethyl acetate, 90:10 to 0:100 gradient). The product was obtained as a yellow solid (71 mg, 24%).

[1046] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.79 (d, J = 3.0 Hz, 2H), 8.07 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 5.7 Hz, 2H), 7.30 (d, J = 8.5 Hz, 1H).

[1047] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 151.95, 149.85, 149.45, 149.11, 142.48, 140.96, 136.61, 131.46, 125.33, 120.29, 88.27.

[1048] HRMS (APCI): Theoretical value (C 12 H7ClIN2S)[M+H] + =372.9058, measured value [M+H] + =372.9054.

[1049] FTIR (NEET), CM -1 :1600, 1559, 1377, 1264, 1152, 1126, 993, 811, 733, 702, 616.

[1050] (Preparation Example 141: 5-Chloro-2-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[1051] [ka]

[1052] To a solution (in which 5-chloro-2-iodo-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 140) (130 mg, 0.349 mmol) was dissolved in dioxane (7 mL)), potassium phosphate (222 mg, 1.05 mmol), methylboronic acid (25 mg, 0.419 mmol), [1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (13 mg, 0.017 mmol), and H2O (1.7 mL) were added, and the mixture was refluxed for 4 hours. Additional potassium phosphate (222 mg, 1.05 mmol) and [1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (13 mg, 0.017 mmol) were added, and the reaction mixture was stirred for a further 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 40:60 gradient). The product was obtained as a white solid (35 mg, 39%).

[1053] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.75(d,J=5.1Hz,2H), 8.04(d,J=8.4Hz,1H), 7.51(dd,J=4.8,1.6Hz,2H), 7.28(s,1H), 2.67(s,3H).

[1054] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 154.15, 149.62, 149.17, 144.64, 141.49, 132.01, 130.67, 125.08, 119.46, 15.81.

[1055] HRMS (APCI): Theoretical value (C 13 H10 ClN2S)[M+H] + =261.0248, measured value [M+H] + = 261.0247.

[1056] FTIR (NEET), CM -1 :3040, 2917, 1604, 1555, 1525, 1493, 1393, 1355, 1153, 1121, 989, 966, 836, 810, 765, 631, 532, 460.

[1057] (Preparation Example 142: 2-methyl-5-(1-methyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1058] [ka]

[1059] To a solution (in which 5-chloro-2-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 141) (25 mg, 0.095 mmol) was dissolved in dioxane (1.5 mL)), potassium phosphate (61 mg, 0.288 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (24 mg, 0.115 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (4 mg, 0.005 mmol), and H2O (0.3 mL) were added, and the mixture was refluxed for 4 hours. Additional potassium phosphate (30 mg, 0.144 mmol) and [1,1'-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II) (4 mg, 0.005 mmol) were added, and the reaction mixture was stirred for a further 6 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 100:0 gradient). The product was obtained as a yellow solid (25 mg, 86%).

[1060] 1H NMR(500MHz,Chloroform-d)δ(ppm)8.76(s,2H), 8.06(d,J=8.4Hz,1H), 7.94(s,1H), 7.88(s,1H), 7.62(d,J=5.3Hz,2H), 7.43(d,J=8.4Hz,1H), 3.95(s,3H), 2.68(s,3H).

[1061] 13 C NMR(126MHz,Chloroform-d)δ(ppm)154.28, 149.63, 148.95, 143.21, 142.80, 1 37.59, 130.73, 130.17, 129.47, 129.00, 125.49, 123.93, 115.38, 39.18, 15.75.

[1062] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1010.

[1063] FTIR (NEET), CM -1 :3089, 2916, 2848, 1716, 1595, 1573, 1535, 1433, 1227, 1187, 1142, 995, 983, 937, 829, 811, 705, 629, 577, 564, 519, 475.

[1064] (Preparation Example 143: 2-methyl-5-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1065] [ka]

[1066] To a solution (in which 5-chloro-2-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 141) (15 mg, 0.057 mmol) was dissolved in dioxane (1 mL), potassium phosphate (37 mg, 0.172 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (14 mg, 0.069 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2 mg, 0.003 mmol), and H2O (0.2 mL) were added, and the mixture was refluxed for 2.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / cyclohexane, 0:100 to 100:0 gradient) and TLC for preparation (siRNA / cyclohexane, 50:50 gradient, 4 elutions). The product was obtained as a white solid (5 mg, 30%).

[1067] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.77(s,2H), 8.12(d,J=8.4Hz,1H), 8.00(d,J=8.4Hz,1H), 7.77(d,J=5.1Hz,2H), 7.39(d,J=2.1Hz,1H), 6.86(d,J=2.2Hz,1H), 3.98(s,3H), 2.72(s,3H).

[1068] 13 C NMR(126MHz,Chloroform-d)δ(ppm)153.80, 152.17, 150.15, 147.53, 144.12, 1 43.72, 131.53, 130.73, 130.32, 130.16, 125.85, 115.71, 104.83, 39.21, 15.89.

[1069] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1009.

[1070] FTIR (NEET), CM-1 :2953, 2921, 2852, 1632, 1600, 1557, 1435, 1397, 1335, 1155, 1112, 829, 632.

[1071] (Preparation Example 144: tert-butyl(2-bromothiophene-3-yl)carbamate (intermediate))

[1072] [ka]

[1073] N-bromosuccinimide (893 mg, 5.02 mmol) was added to a solution (tert-butylthiophene-3-ylcarbamate (1.00 g, 5.02 mmol) dissolved in chloroform (12 mL)), and the reaction mixture was refluxed for 3 hours. The mixture was quenched with saturated aqueous Na2S2O3 (15 mL) and extracted with dichloromethane (20 mL). The integrated organic extract was dried over MgSO4 and then filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 90:10 gradient). The product was obtained as a pale yellow solid (1.36 g, 97%).

[1074] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.56 (br s, 1H), 7.23 (d, J = 5.9Hz, 1H), 6.55 (br s, 1H), 1.52 (s, 9H).

[1075] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.14, 135.74, 124.78, 121.67, 81.15, 28.27.

[1076] FTIR (NEET), CM -1 :2978, 1727, 1579, 1478, 1381, 1367, 1230, 1156, 1072, 1000, 943, 879, 709.

[1077] (Preparation Example 145: tert-butyl(2-bromothiophene-3-yl)(methacryloyl)carbamate (intermediate))

[1078] [ka]

[1079] To a solution (100 mg, 0.359 mmol) of tert-butyl(2-bromothiophene-3-yl)carbamate (Preparation Example 144) dissolved in THF (1.5 mL), sodium hydride (60% in oil, 17 mg, 0.431 mmol) was added at -10°C. After stirring for 5 minutes, methacryloyl chloride (42 μL, 0.431 mmol) was added to the reaction mixture. Reaction time: 40 minutes. The mixture was quenched with saturated NaHCO3 aqueous solution (2 mL) and extracted with ethyl acetate (10 mL x 2). The integrated organic extract was washed with H2O (8 mL) and saline solution (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. After evaporating the solvent, the residue was purified by flash chromatography (cyclohexane / ethyl acetate, 100:0 to 85:15 gradient). The product was obtained as a pale yellow waxy substance (109 mg, 88%).

[1080] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 7.28(d,J=5.8Hz,1H), 6.81(d,J=5.8Hz,1H), 5.62(s,1H), 5.38(s,1H), 2.07(s,3H), 1.45(s,9H).

[1081] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 172.56, 151.76, 142.14, 135.81, 126.70, 125.10, 119.04, 110.74, 83.93, 27.75, 26.92, 19.12.

[1082] FTIR (NEET), CM -1:2979, 1739, 1692, 1382, 1370, 1279, 1247, 1151, 1112.

[1083] (Preparation Example 146: 6-methylthieno[3,2-b]pyridine-5(4H)-one (intermediate))

[1084] [ka]

[1085] To a solution (400 mg, 1.15 mmol) of tert-butyl (2-bromothiophene-3-yl) (methacryloyl) (Preparation Example 145) dissolved in N,N-dimethylacetamide (5.5 mL), potassium acetate (451 mg, 4.60 mmol), XPhos (27 mg, 0.0575 mmol), and PdXPhosG3 (97 mg, 0.115 mmol) were added, and the reaction mixture was stirred at 130 °C for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 0:100 to 95:5 gradient). The product was obtained as an orange waxy substance (92 mg, 48%).

[1086] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.55 (d, J = 5.3 Hz, 1H), 7.18 (d, J = 5.4 Hz, 1H), 6.42 (s, 1H), 2.44 (s, 3H).

[1087] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 165.27, 146.97, 141.66, 129.49, 121.21, 117.60, 115.49, 20.22.

[1088] HRMS (APCI): Theoretical value (C8H8NOS) [M+H] + =166.0321, measured value [M+H] + = 166.0318.

[1089] FTIR (NEET), CM-1 :2922, 1633, 1540, 1459, 1428, 1375, 1205, 1120, 954, 923, 833, 768, 734, 711, 670, 590, 512, 413.

[1090] (Preparation Example 147: 5-chloro-6-methylthieno[3,2-b]pyridine (intermediate))

[1091] [ka]

[1092] To a solution (6-methylthieno[3,2-b]pyridine-5(4H)-one (Preparation Example 146) (103 mg, 0.623 mmol) dissolved in phosphate chloride (3.5 mL, 37.4 mmol), phosphorus pentachloride (194 mg, 0.934 mmol) was added, and the reaction mixture was stirred at 70°C for 16 hours. An additional phosphorus pentachloride (78 mg, 0.374 mmol) was added, and the mixture was stirred for a further 4 hours. The reaction mixture was quenched with saturated NaHCO3 aqueous solution to adjust the pH to 7 at -20°C, and H2O (30 mL) was added. The resulting mixture was extracted with siRNA (50 mL). The integrated organic extract was dried over MgSO4 and then filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 100:0:0 to 0:90:10 gradient). The product was obtained as a yellow, waxy substance (57 mg, 50%).

[1093] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.76 (d, J = 5.4 Hz, 1H), 7.52 (d, J = 5.5 Hz, 1H), 7.12 (s, 1H), 2.58 (s, 3H).

[1094] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 155.19, 149.21, 144.27, 132.70, 131.10, 124.91, 119.42, 19.89.

[1095] HRMS(APCI): Theoretical value (C8H7ClNS)[M+H] + =183.9982, measured value [M+H] + = 183.9980.

[1096] FTIR (NEET), CM -1 :1554, 1437, 1361, 1299, 1248, 1142, 1030, 887, 815, 774, 704, 624, 542, 498.

[1097] (Preparation Example 148: 3-bromo-5-chloro-6-methylthieno[3,2-b]pyridine (intermediate))

[1098] [ka]

[1099] To a solution (5-chloro-6-methylthieno[3,2-b]pyridine (Preparation Example 147) (77 mg, 0.419 mmol) dissolved in chloroform (4 mL)), sodium bicarbonate (35 mg, 0.419 mmol), magnesium sulfate (76 mg, 0.628 mmol), and potassium hydrogen phosphate (109 mg, 0.628 mmol) were added, and the reaction mixture was refluxed for 30 minutes. Additional bromine (160 μL, 3.10 mmol) was added in installments over 48 hours. The reaction mixture was quenched with saturated Na2S2O3 aqueous solution (20 mL), and the resulting mixture was extracted with dichloromethane (2 × 20 mL). The integrated organic extract was dried over MgSO4 and then filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 97:3 gradient). The product was obtained as a pale yellow solid (74 mg, 67%).

[1100] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.77 (s, 1H), 7.19 (s, 1H), 2.58 (d, J = 0.7Hz, 3H).

[1101] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 151.56, 150.57, 144.53, 131.69, 127.65, 120.71, 109.82, 19.17.

[1102] HRMS(APCI): Theoretical value (C8H6BrClNS)[M+H] + =261.9087, measured value [M+H] + = 261.9090.

[1103] FTIR (NEET), CM -1 :3069, 1554, 1481, 1426, 1376, 1357, 1297, 1145, 1077, 1045, 904, 835, 818, 777, 498.

[1104] (Preparation Example 149: 5-Chloro-6-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[1105] [ka]

[1106] To a solution (3-bromo-5-chloro-6-methylthieno[3,2-b]pyridine (Preparation Example 148) (50 mg, 0.190 mmol) dissolved in dioxane (3 mL)), potassium phosphate (69 mg, 0.327 mmol), pyridine-4-ylboronic acid (28 mg, 0.228 mmol), [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (4 mg, 0.005 mmol), and H2O (0.6 mL) were added, and the reaction mixture was refluxed for 2 hours. Additional potassium phosphate (35 mg, 0.164 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 equivalents, 4 mg, 0.005 mmol) were added, and the reaction mixture was refluxed for a further 30 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 20:80 gradient). The product was obtained as a pale yellow solid (31 mg, 63%).

[1107] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.72 (d, J = 4.6 Hz, 2H), 8.05 (s, 1H), 7.98 (d, J = 5.5Hz, 2H), 7.21 (s, 1H), 2.62 (s, 3H).

[1108] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.13, 150.02, 149.80, 144.43, 141.26, 133.96, 133.93, 129.53, 122.47, 120.24, 19.73.

[1109] HRMS (APCI): Theoretical value (C 13 H 10 ClN2S)[M+H] + =261.0248, measured value [M+H] + = 261.0246.

[1110] (Preparation Example 150: 6-methyl-5-(1-methyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1111] [ka]

[1112] To a solution (5-chloro-6-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 149) (24 mg, 0.092 mmol) dissolved in dioxane (2 mL)), potassium phosphate (58 mg, 0.276 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (23 mg, 0.110 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (7 mg, 0.010 mmol), and H2O (0.4 mL) were added, and the reaction mixture was refluxed for 1 hour. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:98:2 gradient). The product was obtained as a pale yellow solid (24 mg, 86%).

[1113] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.73(s,2H), 8.12(d,J=4.2Hz,2H), 8.03(d,J=3.8Hz,2H), 8.00(s,1H), 7.36(s,1H), 4.00(s,3H), 2.64(s,3H).

[1114] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.76, 150.46, 149.54, 142.45, 142.03, 1 37.78, 134.00, 132.62, 129.08, 128.78, 123.92, 122.77, 116.46, 39.25, 19.98.

[1115] HRMS (APCI): Theoretical value (C 17 H 15 N4)[M+H] + =307.1012, measured value [M+H] += 307.1012.

[1116] FTIR (NEET), CM -1 :3397, 3093, 2932, 1597, 1585, 1549, 1416, 1200, 998, 850, 829, 788, 703, 638, 530.

[1117] (Preparation Example 151: 6-methyl-5-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1118] [ka]

[1119] To a solution (in which 5-chloro-6-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 149) (35 mg, 0.134 mmol) was dissolved in dioxane (2 mL)), potassium phosphate (85 mg, 0.402 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (33 mg, 0.161 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8 mg, 0.010 mmol), and H2O (0.5 mL) were added, and the reaction mixture was refluxed for 2 hours. The solvent was evaporated, and the residue was purified twice by TLC preparation (siRNA, 100%, eluted twice; cyclohexane / siRNA, 50:50, eluted once; cyclohexane, 100%, eluted three times; toluene, 100%, eluted twice). The product was obtained as a pale yellow solid (11 mg, 27%).

[1120] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.73(d,J=6.3Hz,2H), 8.15(d,J=6.4Hz,2H), 8.03(s, 1H), 7.93(s,1H), 7.44(d,J=2.3Hz,1H), 7.03(d,J=2.3Hz,1H), 4.01(s,3H), 2.66(s,3H).

[1121] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.60, 152.38, 150.80, 149.98, 142.06, 1 42.04, 134.30, 133.87, 131.60, 128.34, 122.66, 116.39, 105.02, 39.24, 19.90.

[1122] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1015.

[1123] FTIR (NEET), CM -1 :3671~2780, 1598, 1579, 1558, 1368, 1280, 1205, 829, 776, 765, 728, 638, 531.

[1124] (Preparation Example 152: N-(thiophen-3-yl)acetamide (intermediate))

[1125] [ka]

[1126] The solution (thiophene-3-amine (214 mg, 1.58 mmol) dissolved in acetic anhydride (2.9 mL)) was stirred at 25°C for 2.5 hours. The reaction mixture was quenched with H2O (7 mL) and stirred for 15 minutes. Next, NaOH (6 M) was added to adjust the pH to 9, and the resulting mixture was extracted with dichloromethane (3 × 20 mL). The integrated organic extract was washed with saline solution (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. The product was obtained as a brown solid (203 mg, 91%).

[1127] 1H NMR(500MHz,Chloroform-d)δ(ppm)7.54(dd,J=3.1,1.2Hz,2H), 7.22(dd,J=5.1,3.2Hz,1H), 6.98(dd,J=5.2,1.3Hz,1H), 2.16(s,3H).

[1128] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 167.44, 135.53, 124.49, 120.91, 110.29, 23.88.

[1129] HRMS (APCI): Theoretical Value (C6H8NOS) [M+H] + =142.0321, measured value [M+H] + =142.0322.

[1130] FTIR(ニート)、cm -1 :3267, 3221, 1654, 1572, 1544, 1375, 1362, 1294, 1151, 839, 772, 750, 725, 597.

[1131] (Preparation Example 153: 7-メチルチエノ[3,2-b]ピリジン-5(4H)-オン (intermediate))

[1132]

change

[1133] To a solution (450 mg, 3.19 mmol of N-(thiophen-3-yl)acetamide (Preparation Example 152) dissolved in 6 mL of isopropanol), 0.56 mL, 4.78 mmol of ethyl buto-2-inoate, 97 mg, 0.160 mmol of dichloro(p-cymene)ruthenium(II) dimer, 279 mg, 0.638 mmol of silver(V) hexafluoride, and 3.26 g, 31.9 mmol of pivalic acid were added in a sealed tube, and the reaction mixture was stirred at 130°C for 22 hours. Additional pivalic acid (2.15 g, 21.0 mmol) was added, and the reaction mixture was stirred for a further 24 hours. Next, additional dichloro(p-cymene)ruthenium(II) dimer (97 mg, 0.160 mmol), silver(V) hexafluoride antimonate (279 mg, 0.638 mmol), and pivalic acid (3.26 g, 31.9 mmol) were added, and the reaction was stirred for a further 72 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (dichloromethane / methanol, gradient from 100:0 to 80:20). The product was obtained as a brown solid (250 mg, 48%).

[1134] 1 H NMR (500MHz, Methanol-d4) δ (ppm) 7.80 (d, J = 5.4 Hz, 1 H), 7.11 (d, J = 5.4 Hz, 1 H), 6.49~6.21 (m, 1 H), 2.45 (d, J = 1.0 Hz, 3 H).

[1135] 13 C NMR (126MHz, Methanol-d4) δ (ppm) 165.85, 149.07, 142.89, 131.78, 122.51, 118.10, 115.88, 20.06.

[1136] HRMS (APCI): Theoretical value (C8H8NOS) [M+H] + =166.0321, measured value [M+H] + = 166.0319.

[1137] FTIR (NEET), CM -1:2921, 1724, 1642, 1572, 1542, 1457, 1432, 1375, 1212, 838, 659.

[1138] (Preparation Example 154: 5-chloro-7-methylthieno[3,2-b]pyridine (intermediate))

[1139] [ka]

[1140] The solution (7-methylthieno[3,2-b]pyridine-5(4H)-one (Preparation Example 153) (200 mg, 1.21 mmol) dissolved in phosphorus(V) oxychloride (7 mL, 72.3 mmol)) was stirred at 70°C for 3 hours. Next, triethylamine (0.26 mL) was added, and the reaction mixture was stirred for 16 hours. The reaction mixture was quenched with NaOH (6 M) and the pH was adjusted to 7 at -30°C. The resulting mixture was extracted with siRNA (2 × 30 mL) and washed with H₂O (30 mL). The integrated organic extract was washed with saline solution (2 × 15 mL), dried over MgSO₄, and filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 90:10 gradient). The product was obtained as a yellow waxy substance (107 mg, 48%).

[1141] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.75 (d, J = 5.5 Hz, 1 H), 7.51 (d, J = 5.5 Hz, 1 H), 7.12 (s, 1 H), 2.58 (d, J = 0.6 Hz, 3 H).

[1142] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 155.38, 149.35, 144.11, 132.64, 130.95, 125.04, 119.41, 19.88.

[1143] HRMS(APCI): Theoretical value (C8H7ClNS)[M+H] + =183.9982, measured value [M+H] + = 183.9984.

[1144] FTIR (NEET), CM -1 :1554, 1437, 1361, 1299, 1248, 1142, 1030, 887, 815, 774, 704, 624, 542, 498.

[1145] (Preparation Example 155: 3-bromo-5-chloro-7-methylthieno[3,2-b]pyridine (intermediate))

[1146] [ka]

[1147] To a solution (5-chloro-7-methylthieno[3,2-b]pyridine (Preparation Example 154) (76 mg, 0.413 mmol) dissolved in chloroform (3 mL), sodium bicarbonate (35 mg, 0.413 mmol), magnesium sulfate (75 mg, 0.620 mmol), and potassium hydrogen phosphate (108 mg, 0.620 mmol) were added, and the mixture was refluxed for 30 minutes. Next, bromine (39 μL, 0.758 mmol) was added, and the reaction mixture was stirred for 16 hours. The reaction mixture was quenched with saturated Na2S2O3 aqueous solution (20 mL), and the resulting mixture was extracted with dichloromethane (4 × 15 mL). The integrated organic extract was dried over MgSO4 and then filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 95:5 gradient). The product was obtained as a pale yellow solid (61 mg, 56%).

[1148] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.77 (s, 1H), 7.20 (s, 1H), 2.58 (br s, 3H).

[1149] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 151.58, 150.59, 144.53, 131.70, 127.65, 120.72, 109.84, 19.18.

[1150] HRMS (APCI): Theoretical value (C8H6BrClNS = 261.9087, measured value [M+H]) + = 261.9089.

[1151] FTIR (NEET), CM -1 :3074, 2923, 1557, 1378, 1359, 1299, 1150, 906, 839, 818, 781.

[1152] (Preparation Example 156: 5-Chloro-7-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[1153] [ka]

[1154] To a solution (3-bromo-5-chloro-7-methylthieno[3,2-b]pyridine (Preparation Example 155) (58 mg, 0.221 mmol) dissolved in dioxane (6 mL)), potassium phosphate (141 mg, 0.630 mmol), pyridine-4-ylboronic acid (33 mg, 0.265 mmol), [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (8 mg, 0.011 mmol), and H2O (0.5 mL) were added, and the mixture was refluxed for 5 hours. Additional potassium phosphate (141 mg, 0.063 mmol) and [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8 mg, 0.011 mmol) were added, and the reaction mixture was refluxed for a further 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 60:40 to 0:100 gradient). The product was obtained as a pale yellow solid (22 mg, 39%).

[1155] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.72 (dd, J = 4.7, 1.3 Hz, 2H), 8.06 (s, 1H), 7.98 (d, J = 6.1 Hz, 2H), 7.21 (s, 1H), 2.62 (d, J = 0.7 Hz, 3H).

[1156] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.14, 149.97, 149.81, 144.43, 141.32, 133.94, 129.55, 122.49, 120.25, 19.74.

[1157] HRMS (APCI): Theoretical value (C 13 H 10 ClN2S)[M+H] + =261.0248, measured value [M+H] + = 261.0246.

[1158] FTIR (NEET), CM -1 :3065, 2918, 1601, 1558, 1435, 1379, 1362, 1302, 1212, 1144, 992, 853, 833, 811, 641, 563, 532.

[1159] (Preparation Example 157: 7-methyl-5-(1-methyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1160] [ka]

[1161] To a solution (5-chloro-7-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 156) (20 mg, 0.077 mmol) dissolved in dioxane (1.5 mL)), potassium phosphate (49 mg, 0.231 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (19 mg, 0.092 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (3 mg, 0.004 mmol), and H2O (0.3 mL) were added, and the mixture was refluxed for 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 100:0 to 90:10 gradient). The product was obtained as a pale yellow solid (18 mg, 77%).

[1162] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.74(s,2H), 8.12(d,J=4.5Hz,2H), 8.03(d,J=4.7Hz,2H), 8.00(s,1H), 7.36(s,1H), 4.00(s,3H), 2.64(s,3H).

[1163] 13 C NMR(126MHz,Chloroform-d)δ(ppm)152.78, 150.42, 149.82, 142.15, 141.98, 1 37.77, 134.10, 132.60, 129.06, 128.58, 123.94, 122.71, 116.40, 39.22, 19.95.

[1164] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1009.

[1165] FTIR (NEET), CM -1 :3081, 1585, 1556, 1517, 1412, 1197, 987, 845, 811, 698, 648, 529.

[1166] (Preparation Example 158: 7-methyl-5-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1167] [ka]

[1168] To a solution (in which 5-chloro-7-methyl-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 156) (32 mg, 0.122 mmol) was dissolved in dioxane (2.5 mL)), potassium phosphate (78 mg, 0.366 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (28 mg, 0.134 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (5 mg, 0.006 mmol), and H2O (0.6 mL) were added, and the mixture was refluxed for 2 hours. Additional potassium phosphate (38 mg, 0.183 mmol) and [1,1'-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II) (5 mg, 0.006 mmol) were added, and the reaction mixture was refluxed for a further 45 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 10:90 gradient) and reverse-phase TLC (methanol / H2O, 98:2). The product was obtained as a white solid (10 mg, 28%).

[1169] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.73(dd,J=4.6,1.4Hz,2H), 8.15(dd,J=4.6,1.6Hz,2H),8. 03(s,1H), 7.93(s,1H), 7.44(d,J=2.2Hz,1H), 7.03(d,J=2.2Hz,1H), 4.01(s,3H), 2.66(s,3H).

[1170] 13C NMR(126MHz,Chloroform-d)δ(ppm)152.58, 152.36, 150.78, 149.95, 142.06, 1 42.03, 134.26, 133.86, 131.60, 128.35, 122.65, 116.37, 105.01, 39.25, 19.91.

[1171] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1015.

[1172] FTIR (NEET), CM -1 :3413, 3097, 2924, 2853, 1632, 1598, 1580, 1521, 1367, 1280, 1206, 829, 777, 765, 702, 638, 530.

[1173] (Preparation Example 159: 5,7-Dichlorothieno[3,2-b]pyridine (intermediate))

[1174] [ka]

[1175] To a solution (1.32 g, 9.67 mmol) of thiophene-3-amine hydrochloride dissolved in oxalate (12 mL, 128 mmol), malonic acid (1.00 g, 9.67 mmol) was added, and the mixture was stirred in a sealed tube at 100°C for 16 hours. The reaction mixture was dissolved in toluene (40 mL) at -60°C, followed by the addition of H₂O (30 mL). Then, saturated NaOH aqueous solution was added dropwise to adjust the pH to 7. The integrated organic extract was washed with saline solution (30 mL), dried over MgSO₄, and filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / toluene, 50:50). The product was obtained as a brown solid (852 mg, 43%).

[1176] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.84 (d, J = 5.5 Hz, 1H), 7.53 (d, J = 5.5 Hz, 1H), 7.34 (s, 1H).

[1177] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 156.30, 149.24, 139.58, 132.82, 131.71, 125.20, 118.82.

[1178] HRMS(APCI): Theoretical value (C7H4Cl2NS)[M+H] + =203.9436, measured value [M+H] + = 203.9436.

[1179] FTIR (NEET), CM -1 :3091, 3068, 1557, 1526, 1484, 1353, 1220, 1142, 837, 815, 770, 701.

[1180] (Preparation Example 160: 3-bromo-5,7-dichlorothieno[3,2-b]pyridine (intermediate))

[1181] [ka]

[1182] To a solution (5,7-dichlorothieno[3,2-b]pyridine (Preparation Example 159) (300 mg, 1.47 mmol) dissolved in chloroform (7 mL)), sodium bicarbonate (123 mg, 1.47 mmol), magnesium sulfate (265 mg, 2.21 mmol), and potassium hydrogen phosphate (314 mg, 2.05 mmol) were added. The reaction mixture was refluxed for 5 minutes, followed by the addition of bromine (140 μL, 2.72 mmol). After 3 hours, an additional bromine (50 μL, 0.975 mmol) was added, and the mixture was refluxed for a further 24 hours. The reaction mixture was quenched with saturated Na2S2O3 aqueous solution (30 mL), and the resulting mixture was extracted with dichloromethane (2 × 25 mL). The integrated organic extract was dried over MgSO4 and then filtered. The solvent was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / Â, 10:90). The product was obtained as a white solid (343 mg, 82%).

[1183] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 7.86 (s, 1H), 7.43 (s, 1H).

[1184] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.60, 150.48, 139.83, 130.80, 129.51, 120.03, 109.90.

[1185] HRMS(APCI): Theoretical value (C7H3BrCl2NS)[M+H] + =281.8541, measured value [M+H] + = 281.8542.

[1186] FTIR (NEET), CM -1 :3074, 1556, 1517, 1477, 1344, 1260, 1143, 1053, 845, 814, 770, 550.

[1187] (Preparation Example 161: 5,7-Dichloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[1188] [ka]

[1189] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 160) (100 mg, 0.182 mmol) dissolved in dioxane (4 mL)), potassium phosphate (224 mg, 1.06 mmol), pyridine-4-ylboronic acid (48 mg, 0.388 mmol), [1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (21 mg, 0.028 mmol), and H2O (1 mL) were added, and the reaction mixture was refluxed for 4 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 20:80 gradient). The product was obtained as a white solid (57 mg, 58%).

[1190] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.74 (dd, J = 4.7, 1.5 Hz, 2H), 8.15 (s, 1H), 7.98 (dd, J = 4.7, 1.6 Hz, 2H), 7.45 (s, 1H).

[1191] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 153.03, 149.78, 149.73, 141.10, 139.91, 134.14, 133.01, 131.33, 122.53, 119.67.

[1192] HRMS (APCI): Theoretical value (C 12 H7Cl2N2S)[M+H] + =280.9702, measured value [M+H] + = 280.9705.

[1193] FTIR (NEET), CM -1:3030, 1601, 1560, 1513, 1354, 1270, 1143, 845, 815, 776, 717, 634, 557, 535.

[1194] (Preparation Example 162: 7-Chloro-5-(1-methyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1195] [ka]

[1196] To a solution (5,7-dichloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 161) (48 mg, 0.170 mmol) dissolved in dioxane (3 mL)), potassium phosphate (108 mg, 0.510 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (39 mg, 0.187 mmol), [1,1'-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) (10 mg, 0.014 mmol), and H2O (0.6 mL) were added, and the reaction mixture was refluxed for 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 0:100 gradient). The product was obtained as a white solid (30 mg, 54%).

[1197] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.76 (s, 2H), 8.10 (s, 3H), 8.03 (s, 1H), 7.99 (s, 1H), 7.55 (s, 1H), 4.01 (s, 3H).

[1198] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 154.02, 151.37, 149.86, 141.73, 138.69, 137.91, 134.38, 131.23, 130.15, 129.35, 123.02, 122.78, 115.65, 39.33.

[1199] HRMS (APCI): Theoretical value (C 16 H 12 ClN4S)[M+H] + =327.0466, measured value [M+H] + =327.0464.

[1200] FTIR (NEET), CM -1 :3424, 3038, 2940, 1598, 1574, 1526, 1181, 1008, 992, 817, 699, 627, 535.

[1201] (Preparation Example 163: 7-Chloro-5-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1202] [ka]

[1203] To a solution (5,7-dichloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 161) (45 mg, 0.160 mmol) dissolved in dioxane (3 mL)), potassium phosphate (102 mg, 0.480 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (37 mg, 0.176 mmol), [1,1'-bis(diphenyl-phosphino)ferrocene]dichloropalladium(II) (10 mg, 0.013 mmol), and H2O (0.6 mL) were added, and the reaction mixture was refluxed for 2.5 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, gradient from 30:70:0 to 0:95:5). The product was obtained as a white solid (29 mg, 56%).

[1204] 1H NMR (500MHz, Chloroform-d) δ(ppm) 8.76(s,2H), 8.24(s,2H), 8.17(s,1H), 8.16(s,1H), 7.46(d,J=2.0Hz,1H), 7.00(d,J=2.1Hz,1H), 4.01(s,3H).

[1205] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 153.58, 152.00, 151.07, 148.34, 143.16, 138.83, 133.81, 132.53, 131.85, 130.75, 123.02, 116.08, 105.25, 39.35.

[1206] HRMS (APCI): Theoretical value (C 16 H 12 ClN4S)[M+H] + =327.0466, measured value [M+H] + = 327.0468.

[1207] FTIR (NEET), CM -1 :3418, 2917, 2849, 1603, 1569, 1545, 1518, 1478, 1434, 1366, 1269, 1057, 811, 767, 760, 630, 533.

[1208] (Preparation Example 164: 5-Chloro-7-methoxy-3-(pyridine-4-yl)thieno[3,2-b]pyridine (intermediate))

[1209] [ka]

[1210] To a solution (5,7-dichloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 161) (100 mg, 0.355 mmol) dissolved in methanol (3 mL)), sodium methoxide (29 mg, 0.532 mmol) and 15-crown-5 (105 μL, 0.532 mmol) were added, and the mixture was refluxed for 16 hours. Additional sodium methoxide (58 mg, 1.06 mmol) and 15-crown-5 (210 μL, 1.06 mmol) were added, and the reaction mixture was refluxed for another 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 30:70 to 50:50 gradient). The product was obtained as a partially impure white solid (39 mg, 40%, purity 70%). This product was used in the next step without further purification.

[1211] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.70~8.67(m,2H), 7.97(s,1H), 7.96~7.94(m,2H), 6.79(s,1H), 4.06(s,3H).

[1212] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 162.18, 153.19, 151.14, 150.42, 149.16, 142.03, 130.10, 122.62, 121.40, 101.54, 56.32.

[1213] HRMS (APCI): Theoretical value (C 13 H 10 ClN2OS)[M+H] + =277.0197, measured value [M+H] + =277.0196.

[1214] (Preparation Example 165: 7-Methoxy-5-(1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine)

[1215] [ka]

[1216] To a solution (5-chloro-7-methoxy-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 164) (34 mg, 0.123 mmol) dissolved in dioxane (3 mL)), potassium phosphate (78 mg, 0.369 mmol), 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (30 mg, 0.147 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8 mg, 0.009 mmol), and H2O (0.6 mL) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by three preparation TLCs (cyclohexane / siRNA, 0:100, single elution, and 50:50, double elution; cyclohexane / siRNA, 50:50, single elution, 80:20, single elution, 100:0, single elution; toluene, double elution; toluene:methanol, 95:5, double elution). The product was obtained as a white solid (21 mg, 54%).

[1217] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.72(d,J=5.7Hz,2H), 8.35(d,J=5.7Hz,2H), 8.08(s, 1H), 7.61(s,1H), 7.46(d,J=2.2Hz,1H), 7.02(d,J=2.2Hz,1H), 4.17(s,3H), 4.02(s,3H).

[1218] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 161.55, 154.17, 153.26, 152.29, 147.39, 132.97, 131.76, 130.09, 123.05, 122.71, 105.18, 97.36, 56.02, 39.28.

[1219] HRMS (APCI): Theoretical value (C 17 H 14 N4OS)[M+H] +=323.0961, measured value [M+H] + =323.0958.

[1220] FTIR (NEET), CM -1 :3387, 3093, 2937, 1598, 1564, 1496, 1374, 1325, 1293, 1212, 1096, 848, 830, 771, 729.

[1221] (Preparation Example 166: 5-Chloro-3-(isothiazol-4-yl)thieno[3,2-b]pyridine)

[1222] [ka]

[1223] The compound was prepared using 3-bromo-5-chlorothieno[3,2-b]pyridine (132 mg, 0.531 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isothiazole (135 mg, 0.637 mmol) according to general procedure A. Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / Âr, 0:100 to 10:90 gradient). The product was obtained as a white solid (34 mg, 25%).

[1224] 1 H NMR (500MHz, Chloroform-d) δ9.66(s,1H), 9.08(s,1H), 8.15(d,J=8.62Hz,1H), 8.01(s,1H), 7.36(s,J=8.627.55Hz,1H).

[1225] 13 C NMR (126MHz, Chloroform-d) δ156.16, 152.63, 149.34, 144.56, 133.00, 132.44, 131.46, 128.32, 127.61, 120.03.

[1226] FTIR (NEET), CM -1:3105, 1561, 1529, 1385, 1265, 1224, 1150, 1126, 844, 794, 711, 618, 476.

[1227] HRMS (APCI): Theoretical value (C 10 H6ClN2S2)[M+H] + =252.9655, measured value [M+H] + = 252.9658.

[1228] (Preparation Example 167: 3-(isothiazol-4-yl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (MU1594))

[1229] [ka]

[1230] The compound was prepared according to general procedure B using 5-chloro-3-(isothiazol-4-yl)thieno[3,2-b]pyridine (Preparation Example 165) (30 mg, 0.119 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (31 mg, 0.148 mmol). Reaction time: 8 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 10:90 to 40:60 gradient) and ground in dichloromethane / hexane (0.3 mL:2 mL). The product was obtained as a white solid (19 mg, 60%).

[1231] 1 H NMR (500MHz, Methanol-d4) δ9.91(s,1H), 9.32(s,1H), 8.33(s,1H), 8.30(t,J=4.51Hz,2H), 8.14(s,1H), 7.66(d,J=8.49Hz,1H), 3.99(s,3H).

[1232] 13C NMR (126MHz, Methanol-d4) δ156.62, 152.56, 149.71, 144.06, 137.35, 132.55, 131.40, 131.28, 129.78, 127.90, 127.43, 123.82, 115.71, 37.71.

[1233] FTIR (NEET), CM -1 :3058, 2916, 1568, 1400, 1355, 1217, 1158, 977, 841, 803, 794, 608, 476.

[1234] HRMS (APCI): Theoretical value (C 14 H 11 N4S2)[M+H] + =299.0420, measured value [M+H] + =299.0424.

[1235] (Preparation Example 168: 5-Chloro-N-(4-fluorophenyl)thieno[3,2-b]pyridine-3-amine)

[1236] [ka]

[1237] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.804 mmol) dissolved in toluene (4 mL)), 4-fluoroaniline (92 μL, 0.965 mmol), tert-butoxide sodium (85 mg, 0.885 mmol), and bis(tri-tert-butylphosphine)palladium(0) (21 mg, 0.040 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10). The product was obtained as a pale yellow solid (140 mg, 63%).

[1238] 1H NMR (500MHz, Chloroform-d) δ(ppm) 8.06(d,J=8.4Hz,1H), 7.33(d,J=8.4Hz,1H), 7.25~7.20(m,2H), 7.05(dd,J=9.6,7.7Hz,2H), 6.93(s,2H).

[1239] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 157.83 (d, J = 240.4 Hz), 148.14, 147.84, 138.39 (d, J = 2. 4Hz), 135.02, 133.21, 130.71, 120.30, 119.08(d,J=7.8Hz), 116.07(d,J=22.6Hz), 101.48.

[1240] 19 F NMR (471MHz, Chloroform-d) δ(ppm) -121.89~-121.95(m).

[1241] FTIR (NEET), CM -1 :3385, 3113, 1530, 1505, 1405, 1386, 1217, 1156, 1119, 776, 517.

[1242] HRMS (APCI): Theoretical value (C 13 H9ClFN2S)[M+H] + =279.0154, measured value [M+H] + = 279.0152.

[1243] (Preparation Example 169: N-(4-fluorophenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2409))

[1244] [ka]

[1245] The compound was prepared according to general procedure B using 5-chloro-N-(4-fluorophenyl)thieno[3,2-b]pyridine-3-amine (Preparation Example 167) (50 mg, 0.179 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (45 mg, 0.214 mmol). Reaction time: 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 50:50 to 0:100 gradient). The product was obtained as a white solid (28 mg, 48%).

[1246] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.08(d,J=8.4Hz,1H), 8.06(s,1H), 8.03(s,1H), 7.50(d,J=8.4Hz) ,1H), 7.28~7.26(m,1H), 7.26~7.24(m,1H), 7.12(s,1H), 7.10~7.03(m,2H), 6.87(s,1H), 4.00(s,3H).

[1247] 13 C NMR(126MHz,Chloroform-d)δ(ppm)157.62(d,J=239.8Hz), 148.62, 147.88, 138.81(d,J=2.3Hz), 137.83, 1 35.16, 131.34, 129.47, 128.88, 123.64, 118.82(d,J=7.7Hz), 116.69, 116.00(d,J=22.5Hz), 99.95, 39.23.

[1248] 19 F NMR (471MHz, Chloroform-d) δ (ppm) -122.48~-122.54.

[1249] FTIR (NEET), CM -1 :3372, 1568, 1533, 1505, 1415, 1380, 1213, 984, 821, 735, 502, 482.

[1250] HRMS (APCI): Theoretical value (C17 H 14 FN4S)[M+H] + =325.0918, measured value [M+H] + =325.0917.

[1251] (Preparation Example 170: 5-Chloro-N-(3-fluorophenyl)thieno[3,2-b]pyridine-3-amine)

[1252] [ka]

[1253] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.804 mmol) dissolved in toluene (4 mL)), tert-butoxide sodium (85 mg, 0.89 mmol), bis(tri-tert-butylphosphine)palladium (0) (21 mg, 0.040 mmol), and 3-fluoroaniline (92 μl, 0.97 mmol) were added, and the reaction mixture was refluxed for 24 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10 to 10:90 gradient). The product was obtained as a pale yellow solid (162 mg, 72%). This product was used in the next step without further purification.

[1254] 1 H NMR (500MHz, Chloroform-d) δ8.07(d,J=8.4Hz,1H), 7.33(d,J=8.4Hz,1H), 7.3 0~7.26(m,1H), 7.14(s,1H), 7.11(s,1H), 7.04~6.96(m,2H), 6.68~6.63(m,1H).

[1255] 13C NMR(126MHz,CDCl3)δ(ppm)163.92(d,J=244.5Hz), 148.40, 148.04, 144.08(d,J=10.6Hz), 133.37, 130.78(d, J=9.9Hz), 130.66, 129.01, 120.58, 112.64(d,J=2.6Hz), 107.74(d,J=21.4Hz), 103.74, 103.62(d,J=25.6Hz).

[1256] 19 F NMR (471MHz, Chloroform-d) δ(ppm) -111.65~-111.75(m).

[1257] FTIR (NEET), CM -1 :3381, 3104, 2921, 2852, 1610, 1594, 1570, 1526, 1484, 1455, 1383, 1331, 1248, 1147, 1122, 1048, 965, 838, 811, 795, 772, 760, 572, 519.

[1258] HRMS (APCI): Theoretical value (C 13 H9ClFN2S)[M+H] + 279.0154, measured value [M+H] + 279.0155.

[1259] (Preparation Example 171: N-(3-fluorophenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2473))

[1260] [ka]

[1261] The compound was prepared according to general procedure B using 5-chloro-N-(3-fluorophenyl)thieno[3,2-b]pyridine-3-amine (Preparation Example 169) (80 mg, 0.29 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (71 mg, 0.342 mmol). Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a pale yellow solid (18 mg, 19% yield).

[1262] 1 H NMR(500MHz,Chloroform-d)δ(ppm)8.09(d,J=8.4Hz,1H), 8.06(s,1H), 8.05(s,1H), 7.51(d,J= 8.4Hz,1H), 7.36(s,1H), 7.31~7.27(m,1H), 7.06~7.01(m,3H), 6.68~6.62(m,1H), 4.00(s,3H).

[1263] 13 C NMR(126MHz,Chloroform-d)δ(ppm)163.99(d,J=244.3Hz), 148.82, 147.93, 144.45(d,J=10.6Hz), 138.00, 133.76, 131.56, 130.73 (d, J=10.0Hz), 129.45, 129.13, 123.65, 116.95, 112.45(d, J=2.4Hz), 107.35(d, J=21.5Hz), 103.48(d, J=25.4Hz), 102.22, 39.41.

[1264] 19 F NMR (471MHz, Chloroform-d) δ(ppm) -111.86~-111.96(m).

[1265] FTIR (NEET), CM -1:3368, 3114, 2942, 1617, 1581, 1537, 1493, 1440, 1403, 1215, 1177, 1151, 985, 830, 767, 731, 682, 519.

[1266] HRMS (APCI): Theoretical value (C 17 H 14 FN4S)[M+H] + 325.0918, measured value [M+H] + 325.0922.

[1267] (Preparation Example 172: 5-Chloro-N-(2-fluorophenyl)thieno[3,2-b]pyridine-3-amine)

[1268] [ka]

[1269] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.804 mmol) dissolved in toluene (4 mL)), tert-butoxide sodium (85 mg, 0.89 mmol), bis(tri-tert-butylphosphine)palladium (0) (21 mg, 0.040 mmol), and 2-fluoroaniline (93 μl, 0.97 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 90:10 to 10:90 gradient). The product was obtained as a brown waxy substance (126 mg, 56%). This product was used in the next step without further purification.

[1270] 1 H NMR (500MHz, Chloroform-d) δ(ppm)δ(ppm)8.07(d, J=8.4Hz, 1H), 7.56~7.52(m , 1H), 7.33(d, J=8.4Hz, 1H), 7.19~7.11(m, 3H), 7.07(s, 1H), 6.95~6.89(m, 1H).

[1271] 13C NMR (126MHz, Chloroform-d) δ (ppm) 152.90 (d, J=242.8Hz), 148.52, 148.24, 133.27, 129.01, 124.63 (d, J=3.7Hz) , 121.27(d, J=7.2Hz), 120.78, 120.57, 119.27(d, J=1.8Hz), 116.96(d, J=2.0Hz), 115.75(d, J=19.0Hz), 103.50.

[1272] 19 F NMR (471MHz, Chloroform-d) δ(ppm) -130.88~-130.99(m).

[1273] FTIR (NEET), CM -1 :3391, 3104, 2958, 2924, 2854, 1619, 1572, 1534, 1486, 1459, 1385, 1247, 1184, 1150, 1119, 1099, 1080, 965, 831, 811, 737, 707, 577, 449.

[1274] HRMS (APCI): Theoretical value (C 13 H9ClFN2S)[M+H] + 279.0154, measured value [M+H] + 279.0156.

[1275] (Preparation Example 173: N-(2-fluorophenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2474))

[1276] [ka]

[1277] The compound was prepared according to general procedure B using 5-chloro-N-(2-fluorophenyl)thieno[3,2-b]pyridine-3-amine (Preparation Example 171) (118 mg, 0.420 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (105 mg, 0.504 mmol). Reaction time: 24 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 0:100 gradient). The product was obtained as a pale yellow solid (28 mg, 20% yield).

[1278] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.14 (br s, 1H), 8.11(d, J=8.4Hz, 1H), 1.06(s, 1H), 7.58(td, J=8.4, 1.6Hz, 1H), 7.53(d , J=8.4Hz, 2H), 7.19~7.11(m, 1H), 7.02(s, 1H), 6.94~6.87(m, 1H), 4.01(s, 3H).

[1279] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 152.68 (d, J=242.0Hz), 148.85, 148.20, 137.93, 133.72, 131.51, 131.42 (d, J=10.7Hz), 1 29.30(d, J=6.3Hz), 124.70(d, J=3.7Hz), 123.59, 120.54(d, J=7.2Hz), 116.77, 116.29, 115.48(d, J=19.0Hz), 101.98, 39.41.

[1280] 19 F NMR (471MHz, CDCl3)δ(ppm) -132.57.

[1281] FTIR (NEET), CM -1 :3371, 3115, 3048, 2942, 1619, 1571, 1538, 1486, 1459, 1404, 1244, 1215, 1160, 1100, 985, 824, 745.

[1282] HRMS (APCI): Theoretical value (C 17 H 14 FN4S)[M+H] + 325.0918, measured value [M+H] + 325.0919.

[1283] (Preparation Example 174: 5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[1284] [ka]

[1285] To a solution (5-chlorothieno[3,2-b]pyridine (1.00 g, 5.89 mmol) dissolved in dioxane (15 mL)), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.47 g, 7.07 mmol), tripotassium phosphate (3.75 g, 17.7 mmol), bis(diphenylphosphino)-ferrocene)dichloropalladium(II) (345 mg, 0.471 mmol), and H2O (3 mL) were added, and the reaction mixture was refluxed for 1 hour. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:98:2 gradient). The product was obtained as a pale yellow solid (1.23 g, 97%).

[1286] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.14(d, J=8.4Hz, 1H), 8.02(s, 2H), 7.73(d, J=5.5Hz, 1H), 7.53(d, J=5.5Hz, 1H), 7.45(d, J=8.4Hz, 1H), 3.98(s, 3H).

[1287] 13C NMR (126MHz, Chloroform-d) δ(ppm) 156.10, 149.83, 137.81, 130.86, 130.67, 130.48, 129.00, 125.00, 123.81, 115.67, 39.17.

[1288] FTIR (NEET), CM -1 :3586~3152, 2978, 2928, 1714, 1577, 1538, 1369, 1113, 1035, 981, 946, 880, 812, 784, 730, 684, 671, 481.

[1289] HRMS (APCI): Theoretical value (C 11 H 10 N3S)[M+H] + =216.0590, measured value [M+H] + = 216.0588.

[1290] (Preparation Example 175: 3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[1291] [ka]

[1292] To a solution (5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 173) (1.29 g, 5.61 mmol) dissolved in DMF (15 mL)), N-bromosuccinimide (1.05 g, 5.89 mmol) was added, and the reaction mixture was warmed at 60°C for 2 hours. Additional N-bromosuccinimide (100 mg, 0.562 mmol) was added, and the reaction mixture was stirred for 1 hour. The reaction mixture was quenched with H2O (20 mL) and extracted with ethyl acetate (2 × 20 mL). The integrated organic extract was washed with H2O (3 × 20 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / ethyl acetate, 70:30 to 0:100 gradient). The product was obtained as a pale yellow solid (1.31 g, 79%).

[1293] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.13~8.09 (m, 2H), 8.04~8.02 (m, 1H), 7.73 (s, 1H), 7.50 (d, J=8.4Hz, 1H), 3.98 (s, 3H).

[1294] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 151.80, 150.81, 137.82, 131.20, 129.51, 129.30, 127.26, 123.58, 116.44, 110.25, 39.20.

[1295] FTIR (NEET), CM -1 :3051, 1704, 1578, 1562, 1387, 1217, 1187, 1180, 1158, 995, 940, 817, 784, 773, 650, 615, 412.

[1296] HRMS (APCI): Theoretical value (C 11 H8BrN3S)[M+H] + =293.9695, measured value [M+H] + = 293.9694.

[1297] (Preparation Example 176: N-(2-chlorophenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2498))

[1298] [ka]

[1299] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (200 mg, 0.680 mmol) dissolved in toluene (2 mL)), tert-butoxide sodium (72 mg, 0.75 mmol), bis(tri-tert-butylphosphine)palladium (0) (17 mg, 0.034 mmol), and 2-chloroaniline (87 μl, 0.82 mmol) were added, and the reaction mixture was refluxed for 18 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (dichloromethane / methanol, gradient from 100:0 to 80:20) and (cyclohexane / siRNA, gradient from 100:0 to 0:100). The product was obtained as a white solid (85 mg, yield 37%).

[1300] 1 H NMR (500MHz, Chloroform-d) δ(ppm)8.09(d, J=8.4Hz, 1H), 8.07(s, 1H), 8.03(s, 1H), 7.97(s, 1H), 7.60(dd, J=8.2, 1.4Hz, 1H) , 7.51(d, J=8.4Hz, 1H), 7.44(dd, J=7.9, 1.5Hz, 1H), 7.30~7.26(m, 1H), 7.06(s, 1H), 6.88(td, J=7.6, 1.4Hz, 1H), 4.00(s, 3H).

[1301] 13C NMR (126MHz, Chloroform-d) δ (ppm) 148.92, 148.47, 139.27, 137.96, 133.41, 131.41, 129.9 6, 129.13, 129.09, 127.92, 125.00, 123.75, 121.80, 120.66, 116.77, 115.17, 102.58, 39.45.

[1302] FTIR (NEET), CM -1 :3351, 1600, 1582, 1542, 1444, 1325, 1222, 1036, 988, 816, 732, 703, 644, 564, 432.

[1303] HRMS (APCI): Theoretical value (C 17 H 14 ClN4S)[M+H] + 341.0622, measured value [M+H] + 341.0624.

[1304] (Preparation example 177: 5-chloro-N-(o-tolyl)thieno[3,2-b]pyridine-3-amine)

[1305] [ka]

[1306] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.804 mmol) dissolved in toluene (4 mL)), tert-butoxide sodium (85 mg, 0.89 mmol), BrettPhosPdG3 (58 mg, 0.064 mmol), BrettPhos (34 mg, 0.064 mmol), and o-toluidine (103 μL, 0.966 mmol) were added, and the reaction mixture was refluxed for 96 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 90:10 gradient). The product was obtained as a pale yellow solid (76 mg, 34% yield).

[1307] 1H NMR (500MHz, Chloroform-d) δ (ppm) 8.06 (d, J=8.4Hz, 1H), 7.49 (d, J=6.6Hz, 1H), 7.32 (d, J=8.5 Hz, 1H), 7.26~7.21(m, 2H), 6.96(td, J=7.5, 1.2Hz, 1H), 6.88(s, 1H), 6.80(s, 1H), 2.40(s, 3H).

[1308] 13 C NMR (126MHz, Chloroform-d) δ(ppm) 148.31, 140.65, 135.28, 133.29, 131.19, 130.81, 127.65, 127.07, 122.05, 120.36, 117.36, 102.18, 17.93.

[1309] FTIR (NEET), CM -1 :3395, 1571, 1525, 1483, 1459, 1387, 1346, 1250, 1154, 1120, 1047, 831, 810, 744, 711.

[1310] HRMS (APCI): Theoretical value (C 14 H 12 ClN2S)[M+H] + 275.0404, measured value [M+H] + 275.0402.

[1311] (Preparation Example 178: 5-(1-methyl-1H-pyrazole-4-yl)-N-(o-tolyl)thieno[3,2-b]pyridine-3-amine (MU2497))

[1312] [ka]

[1313] To a solution (5-chloro-N-(o-tolyl)thieno[3,2-b]pyridine-3-amine (Preparation Example 176) (70 mg, 0.26 mmol) dissolved in dioxane (4 mL)), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (64 mg, 0.31 mmol), potassium carbonate (162 mg, 0.765 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (15 mg, 0.020 mmol), and H2O (0.8 mL) were added, and the resulting mixture was refluxed for 18 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 0:100 gradient). The resulting solid was then washed on glass frit with cyclohexane / siRNA (19:1) solution (20 mL). The product was obtained as a brown solid (43 mg, 53% yield).

[1314] 1 H NMR (500MHz, Chloroform-d) δ(ppm)8.08(d, J=8.4Hz, 1H), 8.07(s, 1H), 7.99(s, 1H), 7.54(dd, J=8.5, 1.2Hz, 1H), 7.50 (d, J=8.4Hz, 1H), 7.28~7.23(m, 2H), 7.19(s, 1H), 6.93(td, J=7.4, 1.2Hz, 1H), 6.89(s, 1H), 4.00(s, 3H), 2.45(s, 3H).

[1315] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 148.62, 148.43, 141.03, 137.99, 134.92, 131.44, 131.0 3, 129.45, 128.85, 127.18, 126.34, 123.88, 121.14, 116.67, 115.96, 100.75, 39.42, 17.89.

[1316] FTIR (NEET), CM -1:3376, 1569, 1537, 1484, 1457, 1402, 1326, 1216, 1159, 1047, 985, 823, 754, 715, 647, 615, 538, 486.

[1317] HRMS (APCI): Theoretical value (C 18 H 17 N4S)[M+H] + 321.1168, measured value [M+H] + 321.1165.

[1318] (Preparation Example 179: 5-(1-methyl-1H-pyrazole-4-yl)-N-(2-(trifluoromethyl)phenyl)-thieno[3,2-b]pyridine-3-amine (MU2551))

[1319] [ka]

[1320] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (195 mg, 0.662 mmol) dissolved in toluene (4 mL)), 2-(trifluoromethyl)aniline (100 μL, 0.794 mmol), bis(tri-tert-butylphosphine)palladium (0) (27 mg, 0.053 mmol), and tert-butoxide sodium (95 mg, 0.993 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 50:50 gradient) and preparation TLC (cyclohexane / siRNA, 70:30, single elution, 100:0, single elution). The product was obtained as a pale yellow solid (24 mg, 92%).

[1321] 1H NMR (500MHz, Chloroform-d) δ8.08(d, J=8.4Hz, 1H), 8.05(s, 1H), 8.01(s, 1H), 8.00(s, 1H), 7.75(d, J=8 .3Hz, 1H), 7.65(d, J=7.7Hz, 1H), 7.52(t, J=7.1Hz, 2H), 7.06(s, 1H), 7.00(t, J=7.6Hz, 1H), 4.00(s, 3H).

[1322] 13 C NMR (126MHz, Chloroform-d) δ148.77, 148.19, 140.87 (d, J=1.5Hz), 137.71, 133.07 (d, J=2.8Hz), 131.23, 128.92, 1 28.89, 127.07(q, J=5.4Hz), 125.90, 123.74, 123.51, 119.71, 117.09(q, J=29.4Hz), 116.60, 116.31, 102.99, 39.28.

[1323] 19 F NMR (471MHz, Chloroform-d) δ-61.52.

[1324] FTIR (NEET), CM -1 :3380, 3111, 2937, 1582, 1537, 1464, 1406, 1326, 1289, 1161, 1101, 1058, 985, 824, 750, 652.

[1325] HRMS (APCI): Theoretical value (C 18 H 14 F3N4S)[M+H] + =375.0886, measured value [M+H] + =375.0888.

[1326] (Preparation Example 180: N-(2-ethylphenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2547))

[1327] [ka]

[1328] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (100 mg, 0.339 mmol) dissolved in toluene (3 mL)), 2-ethylaniline (50 μL, 0.407 mmol), bis(tri-tert-butylphosphine)palladium (0) (14 mg, 0.027 mmol), and tert-butoxide sodium (36 mg, 0.373 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a pale yellow solid (62 mg, 55%).

[1329] 1 H NMR (500MHz, Chloroform-d) δ8.10~8.06(m, 2H), 7.97(s, 1H), 7.56(d, J=7.7Hz, 1H), 7.50(d, J=8.4Hz, 1H), 7.30(s, 1H), 7.27( s, 1H), 7.26~7.23(m, 1H), 6.98(td, J=7.4, 1.1Hz, 1H), 6.87(s, 1H), 4.00(s, 3H), 2.83(q, J=7.6Hz, 2H), 1.40(t, J=7.6Hz, 3H).

[1330] 13 C NMR (126MHz, Chloroform-d) δ148.42, 148.31, 140.33, 137.84, 134.98, 132.21, 131.28, 129 .29, 129.10, 128.65, 126.93, 123.76, 121.29, 116.47, 116.39, 100.35, 39.27, 24.54, 13.80.

[1331] FTIR (NEET), CM -1 :3384, 2963, 1580, 1535, 1456, 1403, 1382, 1214, 1160, 1054, 984, 823, 747, 651.

[1332] HRMS (APCI): Theoretical value (C 19 H 19 N4S)[M+H] + 335.1325, measured value [M+H] + = 335.1326.

[1333] (Preparation Example 181: N-(2-(tert-butyl)phenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2546))

[1334] [ka]

[1335] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (100 mg, 0.339 mmol) dissolved in toluene (3 mL)), 2-(tert-butyl)aniline (64 μL, 0.407 mmol), bis(tri-tert-butylphosphine)palladium (0) (14 mg, 0.027 mmol), and tert-butoxide sodium (36 mg, 0.373 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a pale yellow solid (81 mg, 66%).

[1336] 1 H NMR (500MHz, Chloroform-d) δ8.08(d, J=8.4Hz, 2H), 7.95(s, 1H), 7.64(dd, J=8.0, 1.3Hz, 1H), 7.54(s, 1H), 7.49(d, J=8 .4Hz, 1H), 7.45(dd, J=7.9, 1.5Hz, 1H), 7.29(s, 1H), 7.01(td, J=7.9, 1.4Hz, 1H), 6.78(s, 1H), 4.00(s, 3H), 1.58(s, 9H).

[1337] 13C NMR (126MHz, Chloroform-d) δ148.37, 148.33, 141.09, 139.13, 137.85, 135.72, 131.28, 129 .40, 128.56, 126.96, 126.94, 123.87, 121.85, 120.07, 116.39, 98.71, 39.27, 34.62, 30.41.

[1338] FTIR (NEET), CM -1 :3418, 2962, 1571, 1534, 1480, 1447, 1402, 1231, 1160, 1055, 983, 860, 736.

[1339] HRMS (APCI): Theoretical value (C 21 H 23 N4S)[M+H] + 363.1638, measured value [M+H] + =363.1641.

[1340] (Preparation Example 182: N-(2-cyclopropylphenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2565))

[1341] [ka]

[1342] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (82 mg, 0.282 mmol) dissolved in toluene (3 mL)), 2-cyclopropylaniline (45 mg, 0.337 mmol), bis(tri-tert-butylphosphine)palladium (0) (12 mg, 0.023 mmol), and tert-butoxide sodium (54 mg, 0.564 mmol) were added, and the reaction mixture was refluxed for 24 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20). The product was obtained as a pale yellow solid (15 mg, 15%).

[1343] 1 H NMR (500MHz, Chloroform-d) δ8.09(d, J=8.4Hz, 2H), 8.06(s, 1H), 7.95(s, 1H), 7.56(d, J=7.9Hz, 1H), 7.49(d, J=8.4Hz, 1H), 7.29~7. 21(m, 2H), 7.01(s, 1H), 6.90(t, J=7.3Hz, 1H), 4.00(s, 3H), 1.98(ddd, J=13.7, 8.3, 5.6Hz, 1H), 1.17~1.09(m, 2H), 0.87~0.77(m, 2H).

[1344] 13 C NMR (126MHz, Chloroform-d) δ148.51, 148.42, 142.32, 137.86, 134.33, 131.22, 129.67, 129 .16, 128.83, 128.54, 127.25, 123.87, 119.97, 116.47, 113.92, 100.59, 39.27, 11.70, 5.67.

[1345] FTIR (NEET), CM -1 :3366, 2928, 1581, 1535, 1456, 1214, 1160, 985, 824, 746.

[1346] HRMS (APCI): Theoretical value (C 20 H 19 N4S)[M+H] + 347.1325, measured value [M+H] + = 347.1328.

[1347] (Preparation Example 183: N-(2-methoxyphenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2499))

[1348] [ka]

[1349] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (145 mg, 0.490 mmol) dissolved in toluene (2 mL)), tert-butoxide sodium (52 ​​mg, 0.54 mmol), bis(tri-tert-butylphosphine)palladium (0) (13 mg, 0.025 mmol), and o-anisidine (66 μL, 0.59 mmol) were added, and the reaction mixture was refluxed for 20 hours. The solvent was evaporated, and the residue was purified twice by flash chromatography (dichloromethane / methanol, gradient from 100:0 to 80:20, and cyclohexane / siRNA, gradient from 100:0 to 0:100). The product was obtained as a light brown solid (31 mg, yield 19%).

[1350] 1 H NMR (500MHz, Chloroform-d) δ(ppm)8.10(d, J=0.8Hz, 1H), 8.08(d, J=8.3Hz, 1H), 8.05(s, 1H), 7.92(s, 1H), 7.53(dd, J=7.8, 1.5 Hz, 1H), 7.49(d, J=8.4Hz, 1H), 7.02(s, 1H), 7.02~6.97(m, 1H), 6.97~6.94(m, 1H), 6.93~6.89(m, 1H), 4.01(s, 3H), 4.00(s, 3H).

[1351] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 148.43, 148.17, 137.93, 134.24, 132.49, 131.29, 129.1 7, 128.90, 124.83, 123.67, 121.04, 119.92, 116.42, 114.13, 110.47, 100.74, 55.91, 39.25.

[1352] FTIR (NEET), CM -1 :3385, 1584, 1567, 1538, 1520, 1482, 1454, 1421, 1405, 1238, 1219, 1168, 1115, 1030, 987, 856, 816, 745, 715, 646, 564.

[1353] HRMS (APCI): Theoretical value (C 18 H 17 N4OS)[M+H] + 337.1118, measured value [M+H] + 337.1121.

[1354] (Preparation Example 184: 5-(1-methyl-1H-pyrazole-4-yl)-N-(2-(trifluoromethoxy)phenyl)-thieno[3,2-b]pyridine-3-amine (MU2549))

[1355] [ka]

[1356] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (100 mg, 0.339 mmol) dissolved in toluene (3 mL)), 2-(trifluoromethoxy)aniline (67 μL, 0.407 mmol), bis(tri-tert-butylphosphine)palladium (0) (14 mg, 0.027 mmol), and tert-butoxide sodium (36 mg, 0.373 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 50:50 gradient). The product was obtained as a pale yellow solid (86 mg, 65%).

[1357] 1 H NMR (500MHz, Chloroform-d) δ8.09(d, J=8.4Hz, 1H), 8.07~8.05(m, 1H), 8.02(s, 1H), 7.92(s, 1H), 7.62(dd, J=8 .1, 1.4Hz, 1H), 7.52(d, J=8.4Hz, 1H), 7.35~7.28(m, 2H), 7.05(s, 1H), 6.92(td, J=7.9, 1.5Hz, 1H), 4.00(s, 3H).

[1358] 13C NMR (126MHz, Chloroform-d) δ148.74, 148.18, 137.69, 137.42 (d, J=1.4Hz), 135.59, 132.85, 131.24, 128.9 4, 128.83, 127.75, 124.32~117.76 (q, J=258.4Hz), 123.55, 121.43, 119.70, 116.59, 115.19, 102.18, 39.24.

[1359] 19 F NMR (471MHz, Chloroform-d) δ-57.59.

[1360] FTIR (NEET), CM -1 :3374, 1613, 1582, 1542, 1460, 1245, 1216, 1169, 985, 823, 772.

[1361] HRMS (APCI): Theoretical value (C 18 H 14 F3N4OS)[M+H] + 391.0835, measured value [M+H] + =391.0839.

[1362] (Preparation Example 185: N-(2-ethoxyphenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2552))

[1363] [ka]

[1364] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (100 mg, 0.339 mmol) dissolved in toluene (3 mL)), 2-ethoxyaniline (71 mg, 0.407 mmol), bis(tri-tert-butylphosphine)palladium (0) (14 mg, 0.027 mmol), and tert-butoxide sodium (49 mg, 0.509 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20) and two preparation TLCs (cyclohexane / siRNA, 60:40, single elution; 10:90, single elution; toluene, 100%, triple elution; and cyclohexane / siRNA, 70:30, single elution; 100:0, single elution). The product was obtained as a pale yellow solid (11 mg, 9%).

[1365] 1 H NMR (500MHz, Chloroform-d) δ8.18(s, 1H), 8.12~8.10(m, 1H), 8.07(d, J=8.4Hz, 1H), 8.00(s, 1H), 7.50(dd, J=7.9, 1.5Hz, 1H), 7.48(d, J=8.4H) z, 1H), 7.04~6.98(m, 2H), 6.93(dd, J=8.0, 1.4Hz, 1H), 6.88(dd, J=7.5, 1.3Hz, 1H), 4.20(q, J=6.9Hz, 2H), 3.99(s, 3H), 1.62(t, J=6.9Hz, 3H).

[1366] 13 C NMR (126MHz, Chloroform-d) δ148.55, 148.33, 147.21, 137.81, 133.97, 132.61, 131.14, 128 .93, 128.72, 123.87, 121.03, 119.52, 116.30, 113.36, 111.35, 100.10, 64.20, 39.18, 15.13.

[1367] FTIR (NEET), CM -1:3360, 2188, 2149, 1601, 1573, 1541, 1489, 1546, 1405, 1245, 1212, 1128, 1118, 985, 820, 733.

[1368] HRMS (APCI): Theoretical value (C 19 H 19 N4OS)[M+H] + 351.1274, measured value [M+H] + = 351.1276.

[1369] (Preparation Example 186: N-(2-isopropoxyphenyl)-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2550))

[1370] [ka]

[1371] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (100 mg, 0.339 mmol) dissolved in toluene (3 mL)), 2-isopropoxyaniline (61 μL, 0.407 mmol), bis(tri-tert-butylphosphine)palladium (0) (14 mg, 0.027 mmol), and tert-butoxide sodium (36 mg, 0.373 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a brown solid (68 mg, 55%).

[1372] 1H NMR (500MHz, Chloroform-d) δ8.21(s, 1H), 8.14~8.10(m, 1H), 8.07(d, J=8.4Hz, 1H), 8.00(s, 1H), 7.51(dd, J=7.9, 1.5Hz, 1H), 7. 48(d, J=8.4Hz, 1H), 7.03~6.94(m, 3H), 6.87(td, J=7.8, 1.5Hz, 1H), 4.65(hept, J=6.0Hz, 1H), 3.99(s, 3H), 1.51(d, J=6.1Hz, 6H).

[1373] 13 C NMR (126MHz, Chloroform-d) δ148.56, 148.31, 145.93, 137.82, 133.96, 133.74, 131.13, 128 .92, 128.69, 123.91, 121.27, 119.42, 116.30, 113.79, 113.53, 99.94, 71.52, 39.18, 22.44.

[1374] FTIR (NEET), CM -1 :3362, 2974, 1599, 1572, 1538, 1482, 1457, 1242, 1211, 1159, 1117, 1046, 985, 954, 818, 665.

[1375] HRMS (APCI): Theoretical value (C 20 H 21 N4OS)[M+H] + 365.1431, measured value [M+H] + =365.1432.

[1376] (Preparation Example 187: 5-(1-methyl-1H-pyrazole-4-yl)-N-(naphthalene-1-yl)thieno[3,2-b]pyridine-3-amine (MU2548))

[1377] [ka]

[1378] To a solution (3-bromo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 174) (100 mg, 0.339 mmol) dissolved in toluene (3 mL)), naphthalene-1-amine (79 mg, 0.441 mmol), bis(tri-tert-butylphosphine)palladium (0) (14 mg, 0.027 mmol), and tert-butoxide sodium (49 mg, 0.509 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a pale yellow solid (75 mg, 63%).

[1379] 1 H NMR (500MHz, Chloroform-d) δ8.22(d, J=8.2Hz, 1H), 8.11(d, J=8.3Hz, 2H), 8.06(s, 1H), 7.92~ 7.88(m, 1H), 7.78(s, 1H), 7.66(d, J=7.4Hz, 1H), 7.60~7.46(m, 5H), 6.90(s, 1H), 4.01(s, 3H).

[1380] 13 C NMR (126MHz, Chloroform-d) δ148.60, 148.25, 138.16, 137.86, 135.37, 134.70, 131.34, 129.47, 128. 86, 128.70, 126.35, 126.14, 126.10, 125.68, 123.71, 122.00, 121.14, 116.61, 112.83, 101.32, 39.26.

[1381] FTIR (NEET), CM -1 :3384, 3056, 2939, 1569, 1536, 1499, 1407, 1214, 1157, 983, 770, 730.

[1382] HRMS (APCI): Theoretical value (C 21 H 17 N4S)[M+H] + 357.1168, measured value [M+H]+ =357.1169.

[1383] (Preparation Example 188: N-benzyl-5-chlorothieno[3,2-b]pyridine-3-amine)

[1384] [ka]

[1385] To a solution (300 mg, 1.21 mmol of 3-bromo-5-chlorothieno[3,2-b]pyridine dissolved in 6 mL of N,N-dimethylaminoethanol), Cu(0) (8 mg, 0.121 mmol), CuI (23 mg, 0.121 mmol), potassium phosphate (771 mg, 3.63 mmol), and benzylamine (159 μL, 1.45 mmol) were added, and the reaction mixture was heated at 100°C for 42 hours. After this time, additional amounts of Cu(0) (8 mg, 0.121 mmol), CuI (23 mg, 0.121 mmol), and potassium phosphate (771 mg, 3.63 mmol) were added, and the reaction mixture was stirred for 18 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 0:100 gradient). The product was obtained as a brown solid (52 mg, 17%). This product was used in the next step without further purification.

[1386] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.00 (d, J=8.4Hz, 1H), 7.45~7.40 (m, 2H), 7. 39~7.33(m, 2H), 7.31~7.27(m, 1H), 7.26(d, J=8.5Hz, 1H), 6.17(s, 1H), 5.25(br s, 1H), 4.46(s, 2H).

[1387] 13C NMR (126MHz, Chloroform-d) δ(ppm) 147.98, 147.71, 140.66, 138.74, 133.27, 131.32, 128.80, 127.77, 127.56, 119.95, 98.26, 49.68.

[1388] FTIR (NEET), CM -1 :3100, 2958, 2922, 2851, 1729, 1556, 1525, 1493, 1453, 1383, 1261, 1147, 1121, 1027, 965, 832, 795, 737, 697, 590, 464.

[1389] HRMS (APCI): Theoretical value (C 14 H 12 ClN2S)[M+H] + 275.0404, measured value [M+H] + 275.0406.

[1390] (Preparation Example 189: N-benzyl-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine-3-amine (MU2475))

[1391] [ka]

[1392] To a solution (in which N-benzyl-5-chlorothieno[3,2-b]pyridine-3-amine (Preparation Example 187) (52 mg, 0.19 mmol) was dissolved in dioxane (4 mL)), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (48 mg, 0.23 mmol), potassium carbonate (41 mg, 0.19 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (6 mg, 0.08 mmol), and H2O (0.8 mL) were added, and the reaction mixture was refluxed for 4 hours. The reaction mixture was refluxed for 15 hours with the addition of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4 mg, 0.02 mmol), potassium carbonate (41 mg, 0.19 mmol), and [1,1'-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (6 mg, 0.08 mmol). The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 0:100 gradient). The product was obtained as a pale yellow solid (14 mg, 23% yield).

[1393] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.04 (d, J=8.5Hz, 1H), 8.02 (s, 1H), 8.01 (s, 1H), 7.49~ 7.44(m, 3H), 7.40~7.35(m, 2H), 7.32~7.27(m, 1H), 6.12(s, 1H), 4.50(s, 2H), 3.97(s, 3H).

[1394] 13 C NMR (126MHz, Chloroform-d) δ(ppm) 148.28, 141.12, 139.12, 137.79, 131.36, 130.11, 129.05, 128.63, 127.63, 127.29, 116.21, 96.54, 49.64, 39.20.

[1395] FTIR (NEET), CM -1:3354, 3104, 3058, 3029, 2938, 2849, 1669, 1571, 1534, 1494, 1452, 1404, 1357, 1214, 1170, 980, 825, 734, 698, 652, 619, 484.

[1396] HRMS (APCI): Theoretical value (C 18 H 17 N4S)[M+H] + 321.1168, measured value [M+H] + 321.1168.

[1397] (Preparation Example 190: 3-iodo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine)

[1398] [ka]

[1399] To a solution (5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 173) (850 mg, 3.95 mmol) dissolved in DMF (6 mL)), N-iodosuccinimide (1.99 g, 8.30 mmol) was added, and the reaction mixture was heated at 100°C for 24 hours. The reaction mixture was quenched with concentrated sodium thiosulfate (50 mL) and extracted with ethyl acetate (4 × 100 mL). The integrated organic extract was washed with saturated aqueous LiCl solution (10%, 10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / ethyl acetate, 100:0 to 0:100 gradient). The product was obtained as a pale yellow solid (674 mg, 50% yield).

[1400] 1 H NMR (500MHz, Chloroform-d) δ(ppm) 8.12(s, 1H), 8.10(d, J=8.4Hz, 1H), 8.04(s, 1H), 7.89(s, 1H), 7.47(d, J=8.4Hz, 1H), 3.99(s, 3H).

[1401] 13 C NMR (126MHz, Chloroform-d) δ(ppm) 154.32, 150.82, 137.79, 132.33, 130.94, 129.48, 128.44, 123.57, 116.26, 82.70, 39.21.

[1402] FTIR (NEET), CM -1 :3054, 1576, 1381, 1344, 1296, 1256, 1215, 1145, 1048, 984, 928, 852, 834, 811, 773, 705, 646, 611, 539, 483, 407.

[1403] HRMS (APCI): Theoretical value (C 11 H9IN3S)[M+H] + 341.9556, measured value [M+H] + 341.9557.

[1404] (Preparation Example 191: 5-(1-methyl-1H-pyrazole-4-yl)-N-(pyridine-4-yl)thieno[3,2-b]pyridine-3-amine (MU2504))

[1405] [ka]

[1406] To a solution (3-iodo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 189) (70 mg, 0.21 mmol) dissolved in toluene (2 mL)), tert-butoxide sodium (22 mg, 0.23 mmol), 4-aminopyridine (23 mg, 0.25 mmol), BrettPhosPdG3 (19 mg, 0.021 mmol), and BrettPhos (11 mg, 0.021 mmol) were added, and the reaction mixture was refluxed for 18 hours. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (dichloromethane / methanol / methanol with a gradient of 7 M NH3, 100:0:0 to 80:20:2). The product was obtained as a light brown solid (10 mg, yield 16%).

[1407] 1 H NMR (500MHz, Methanol-d4) δ (ppm) 8.30 (s, 1H), 8.28 (d, J=8.5Hz, 1H), 8.26~8.23 (m, 2H), 8.15(s, 1H), 7.69(d, J=8.5Hz, 1H), 7.64(s, 1H), 7.26~7.24(m, 2H), 3.97(s, 3H).

[1408] 13 C NMR (126MHz, Methanol-d4) δ (ppm) 153.33, 150.72, 149.85, 149.04, 138.94, 132.96, 132.89, 131.32, 130.89, 124.81, 118.01, 113.26, 111.13, 39.12.

[1409] FTIR (NEET), CM -1 :3342, 3024, 2933, 1579, 1526, 1405, 1215, 984, 812, 524.

[1410] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + 308.0964, measured value [M+H] + 308.0962.

[1411] (Preparation Example 192: 5-(1-methyl-1H-pyrazole-4-yl)-N-(pyridine-3-yl)thieno[3,2-b]pyridine-3-amine (MU2503))

[1412] [ka]

[1413] To a solution (3-iodo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 189) (60 mg, 0.18 mmol) dissolved in toluene (2 mL)), tert-butoxide sodium (19 mg, 0.20 mmol), 2-aminopyridine (20 mg, 0.18 mmol), BrettPhosPdG3 (16 mg, 0.018 mmol), and BrettPhos (10 mg, 0.018 mmol) were added, and the reaction mixture was refluxed for 60 hours. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (dichloromethane / methanol / triethylamine, gradient from 100:0:0 to 80:20:1). The product was obtained as a light brown solid (16 mg, yield 26%).

[1414] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.66 (s, 1H), 8.23 ​​(s, 1H), 8.11 (d, J=8.4Hz, 1H), 8.06 (s, 1H), 8 .05(s, 1H), 7.67~7.63(m, 1H), 7.53(d, J=8.4Hz, 1H), 7.33~7.27(m, 2H), 7.03(s, 1H), 4.01(s, 3H).

[1415] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 148.88, 147.84, 141.64, 139.16, 137.83, 13 3.44, 131.42, 129.32, 128.96, 123.90, 123.47, 122.73, 116.92, 102.12, 39.26.

[1416] FTIR (NEET), CM -1 :3357, 3106, 3044, 2936, 1578, 1532, 1482, 1299, 1215, 1160, 984, 822, 732, 704, 651, 486.

[1417] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + 308.0964, measured value [M+H] + 308.0966.

[1418] (Preparation Example 193: 5-(1-methyl-1H-pyrazole-4-yl)-N-(pyridine-2-yl)thieno[3,2-b]pyridine-3-amine (MU2502))

[1419] [ka]

[1420] To a solution (3-iodo-5-(1-methyl-1H-pyrazole-4-yl)thieno[3,2-b]pyridine (Preparation Example 189) (60 mg, 0.18 mmol) dissolved in toluene (2 mL)), tert-butoxide sodium (19 mg, 0.20 mmol), 2-aminopyridine (20 mg, 0.18 mmol), BrettPhosPdG3 (16 mg, 0.018 mmol), and BrettPhos (10 mg, 0.018 mmol) were added, and the reaction mixture was refluxed for 24 hours. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (cyclohexane / siRNA, 100:0 to 0:100 gradient). The product was obtained as a light brown solid (21 mg, 38% yield).

[1421] 1H NMR (500MHz, Chloroform-d) δ(ppm)8.35~8.33(m, 1H), 8.17(s, 1H), 8.10(d, J=8.4Hz, 1H), 8.07(s, 1H), 8.05 (s, 1H), 7.96(s, 1H), 7.60~7.56(m, 1H), 7.49(d, J=8.4Hz, 1H), 6.92(dt, 1H), 6.82~6.79(m, 1H), 4.01(s, 3H).

[1422] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 154.74, 148.60, 148.09, 137.98, 137.40, 131.5 1, 131.45, 129.15, 129.04, 124.99, 123.85, 116.59, 115.15, 110.41, 106.85, 39.38.

[1423] FTIR (NEET), CM -1 :3392, 1599, 1577, 1520, 1475, 1421, 1401, 1214, 1143, 979, 833, 821, 773, 730, 649, 617, 521.

[1424] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + 308.0964, measured value [M+H] + 308.0964.

[1425] (Preparation Example 194: 5-(1-methyl-1H-imidazole-2-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine (MU1828))

[1426] [ka]

[1427] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.203 mmol) dissolved in dioxane (3 mL)), 1-methyl-2-(tributylstanyl)-1H-imidazole (84 μL, 0.263 mmol) and bis(tri-tert-butylphosphine)palladium(0) (8 mg, 0.016 mmol) were added. Reaction temperature: 110 °C. After 30 minutes, 1-methyl-2-(tributylstanyl)-1H-imidazole (32 μL, 0.102 mmol) was added to the reaction mixture. After 2 hours, bis(tri-tert-butylphosphine)palladium(0) (8 mg, 0.016 mmol) was added, and the mixture was refluxed for a further 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / Â / methanol, 50:50:0 to 0:90:10 gradient) and TLC for preparation (Â / methanol, 95:5, double elution). The product was obtained as a white solid (19 mg, 32% yield).

[1428] 1 H NMR (500MHz, Chloroform-d) δ8.72~8.70(m, 2H), 8.24(d, J=8.24Hz, 1H), 8.01(s, 1H), 7.90 (dd, J=8.4.43, 1.60Hz, 2H), 7.66(d, J=8.60Hz, 1H), 7.57(d, J=14.45Hz, 2H), 4.04(s, 3H).

[1429] 13 C NMR (126MHz, Chloroform-d) δ152.19, 149.97, 148.28, 141.97, 134.52, 131.97, 131.52, 131.30, 129.66, 123.00, 117.62, 35.09.

[1430] FTIR (NEET), CM -1 :3389, 3096, 1598, 1572, 1555, 1394, 1129, 1075, 827, 790, 725, 658, 640.

[1431] HRMS (APCI): Theoretical value (C16 H 13 N4S)[M+H] + =293.0855, measured value [M+H] + = 293.0856.

[1432] (Preparation Example 195: N-(1,4-dimethyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine (MU1920))

[1433] [ka]

[1434] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (80 mg, 0.325 mmol) and 1,4-dimethyl-1H-pyrazole-3-amine (43 mg, 0.390 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 20:80:0 to 0:90:10 gradient). The product was obtained as a pale yellow solid (70 mg, 67% yield).

[1435] 1 H NMR (500MHz, DMSO-d6) δ8.58 (br s, 1H), 8.56(m, 3H), 8.27(dd, J=4.53, 1.55Hz, 2H), 8.19(d, J=8.91, 1H), 7.45(s, 1H), 7.07(d, J=8.97Hz, 1H), 3.76(s, 3H), 1.89(d, J=0.49Hz, 3H).

[1436] 13 C NMR (126MHz, DMSO-d6) δ155.27, 151.21, 149.52, 146.74, 141.26, 132.27, 130.63, 130.15, 130.05, 123.85, 121.60, 108.02, 107.29, 38.40, 8.19.

[1437] FTIR (NEET), CM -1 :1598, 1578, 1542, 1394, 1349, 1306, 824, 810, 780.

[1438] HRMS (APCI): Theoretical value (C 17 H 16 N5S)[M+H] + =322.1121, measured value [M+H] + =322.1119.

[1439] (Preparation Example 196: 1-Methyl-3-((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)amino)-1H-pyrazole-4-carbonitrile (MU1889))

[1440] [ka]

[1441] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (50 mg, 0.233 mmol) and 3-amino-1-methyl-1H-pyrazole-4-carbonitrile (34 mg, 0.279 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (siRNA / methanol, 100:0:~90:10 gradient). The product was obtained as a pale yellow solid (15 mg, 20% yield).

[1442] 1 H NMR (500MHz, Methanol-d4) δ (ppm) 8.53 (d, J=5.9Hz, 2H), 8.37 (s, 1H), 8.32~8.2 6(m, 2H), 8.19(d, J=8.9Hz, 1H), 8.16(s, 1H), 7.31(d, J=8.9Hz, 1H), 3.90(s, 3H).

[1443] 13C NMR(126MHz, Methanol-d4)δ(ppm)154.74, 152.65, 152.40, 149.87, 144.53, 13 7.85, 133.72, 133.11, 131.61, 128.09, 124.05, 114.45, 109.62, 85.46, 39.74.

[1444] FTIR (NEET), CM -1 :3346~2552, 2217, 1597, 1554, 1518, 1392, 1346, 1157, 1002, 824, 784, 699, 640, 599, 559.

[1445] HRMS (APCI): Theoretical value (C 17 H 13 N6S)[M+H] + =333.0917, measured value [M+H] + = 333.0920.

[1446] (Preparation Example 197: N-(5-isopropyl-1-methyl-1H-pyrazole-3-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine (MU2470))

[1447] [ka]

[1448] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (100 mg, 0.406 mmol) and 5-isopropyl-1-methyl-1H-pyrazole-3-amine (62 μl, 0.487 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20:0~0:100 gradient). The product was obtained as a white solid (55 mg, 39% yield).

[1449] 1H NMR (500MHz, Methanol-d4) δ(ppm)8.70(d, J=5.9Hz, 2H), 7.99(d, J=8.8Hz, 3H), 7.91(s, 1H), 7.06( d, J=9.3Hz, 2H), 6.38(s, 1H), 3.73(s, 3H), 2.93(dt, J=13.7, 6.9Hz, 1H), 1.29(s, 3H), 1.28(s, 3H).

[1450] 13 C NMR (126MHz, Methanol-d4)δ(ppm)153.29, 151.36, 150.15, 149.89, 147.94, 142. 43, 133.25, 132.03, 128.63, 125.33, 122.73, 108.32, 92.65, 35.60, 25.71, 22.32.

[1451] FTIR (NEET), CM -1 :2966, 1600, 1581, 1541, 1484, 1457, 1390, 782.

[1452] HRMS (APCI): Theoretical value (C 19 H 20 N5S)[M+H] + =350.1434, measured value [M+H] + =350.1437.

[1453] (Preparation Example 198: 1-Ethyl-3-((3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-yl)amino)-1H-pyrazole-4-carbonitrile (MU1953))

[1454] [ka]

[1455] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (60 mg, 0.244 mmol) and 3-amino-1-ethyl-1H-pyrazole-4-carbonitrile (72 mg, 0.341 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 70:30 to 0:100 gradient). The product was obtained as a pale yellow solid (9 mg, 11% yield).

[1456] 1 H NMR (500MHz, Chloroform-d) δ(pmm)8.72(d, J=4.97Hz, 2H), 8.14(d, J=8.74Hz, 1H), 8.01(m, 2H), 8.00(s , 1H), 7.94(d, J=8.89Hz, 1H), 7.70(s, 1H), 7.23(s, 1H), 4.15(q, J=7.17Hz, 1H), 1.56(t, J=7.50Hz, 1H).

[1457] 13 C NMR (126MHz, Chloroform-d) δ (pmm) 151.76, 151.64, 151.33, 150.05, 141.73, 133. 02, 133.00, 132.72, 129.48, 127.52, 122.52, 113.06, 108.24, 81.07, 47.98, 14.91.

[1458] FTIR (NEET), CM -1 :2924, 2224, 1580, 1552, 1393, 699.

[1459] HRMS (APCI): Theoretical value (C 18 H 15 N6S)[M+H] + =347.1073, measured value [M+H] + = 347.1074.

[1460] (Preparation Example 199: N-(1,3-dimethyl-1H-pyrazole-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine (MU2472))

[1461] [ka]

[1462] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (100 mg, 0.405 mmol) and 1,3-dimethyl-1H-pyrazole-4-amine (54 mg, 0.486 mmol). After 16 hours, additional 1,3-dimethyl-1H-pyrazole-4-amine (54 mg, 0.486 mmol), cesium carbonate (397 mg, 1.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (15 mg, 0.016 mmol), and 4,5-bis(diphenylphosphin)-9,9-dimethylxanthene (19 mg, 0.032 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / Â / methanol, 50:50:0 to 0:95:5 gradient). The product was obtained as a pale yellow solid (50 mg, 38% yield).

[1463] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.58 (d, J=6.1Hz, 2H), 8.23 ​​(s, 1H), 8.19~8.17 (m, 2 H), 8.02(d, J=8.9Hz, 1H), 7.97(s, 1H), 6.85(d, J=8.9Hz, 1H), 3.81(s, 3H), 2.22(s, 3H).

[1464] 13C NMR (126MHz, Chloroform-d) δ (ppm) 156.71, 152.65, 149.99, 145.20, 141.97, 1 33.34, 132.85, 130.59, 126.10, 125.60, 124.26, 122.49, 109.31, 38.75, 11.08.

[1465] FTIR (NEET), CM -1 :3261, 1602, 1580, 1485, 1444, 1390, 1145, 999, 793, 775, 639, 589.

[1466] HRMS (APCI): Theoretical value (C 17 H 16 N5S)[M+H] + =322.1121, measured value [M+H] + =322.1118.

[1467] (Preparation Example 200: N-(2,5-dimethyl-2H-1,2,3-triazol-4-yl)-3-(pyridine-4-yl)thieno[3,2-b]pyridine-5-amine (MU2408))

[1468] [ka]

[1469] The compound was prepared according to general procedure C using 5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (90 mg, 0.366 mmol) and 2-methyl-2H-1,2,3-triazole-4-amine (65 mg, 0.439 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / Â1 / methanol, 50:50:0 to 0:95:5 gradient). The product was obtained as a white solid (75 mg, 64% yield).

[1470] 1H NMR (500MHz, DMSO-d6) δ(ppm)8.96(s, 1H), 8.60(s, 1H), 8.57(d, J=5.1Hz, 2H), 8.27(d, J= 8.9Hz, 1H), 8.22(dd, J=4.7, 1.5Hz, 2H), 7.07(d, J=8.9Hz, 1H), 4.07(s, 3H), 2.12(s, 3H).

[1471] 13 C NMR (126MHz, DMSO-d6) δ(ppm) 154.50, 151.02, 149.53, 143.25, 141.17, 135.76, 132.68, 130.76, 130.54, 124.60, 121.62, 107.48, 41.22, 9.76.

[1472] FTIR (NEET), CM -1 :2921, 2851, 1593, 1546, 1397, 1306, 1001, 797, 721, 643, 560.

[1473] HRMS (APCI): Theoretical value (C 16 H 15 N6S)[M+H] + =323.1073, measured value [M+H] + = 323.1073.

[1474] (Preparation Example 201: 5-((1,4-dimethyl-1H-pyrazole-3-yl)oxy)-3-(pyridine-4-yl)thieno[3,2-b]pyridine (MU2471))

[1475] [ka]

[1476] To a solution (5-chloro-3-(pyridine-4-yl)thieno[3,2-b]pyridine (Preparation Example 12) (100 mg, 0.405 mmol) dissolved in DMF (3 mL)), cesium carbonate (185 mg, 0.567 mmol), 1,4-dimethyl-1H-pyrazole-3-ol (50 mg, 0.445 mmol), copper(I) cyanide (2 mg, 0.020 mmol), and ethylenediamine (7 μL, 0.065 mmol) were added, and the reaction mixture was refluxed for 16 hours. The reaction mixture was quenched with H2O (20 mL) and extracted with RINKAN (3 × 20 mL). The integrated organic extract was washed with H2O (5 × 20 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 40:60:0 to 98:2:0 gradient). The product was obtained as a pale yellow waxy substance (16 mg, 12%).

[1477] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.55 (d, J=4.3Hz, 2H), 8.17 (d, J=8.7Hz, 1H), 8.06 (s, 1H), 7. 94(dd, J=4.8, 1.4Hz, 2H), 7.21(s, 1H), 7.10(d, J=8.7Hz, 1H), 3.83(s, 3H), 1.89(d, J=0.6Hz, 3H).

[1478] 13 C NMR (126MHz, Chloroform-d) δ (ppm) 161.42, 156.13, 150.48, 149.30, 141.62, 1 33.85, 132.38, 130.14, 129.62, 128.97, 122.07, 108.35, 106.44, 39.15, 7.45.

[1479] FTIR (NEET), CM -1 :3424, 2924, 1599, 1580, 1472, 1443, 1389, 1252, 913, 804, 731.

[1480] HRMS (APCI): Theoretical value (C17 H 15 N4OS)[M+H] + =323.0961, measured value [M+H] + =323.0959.

[1481] (Preparation Example 202: 5-(1-methyl-1H-imidazole-2-yl)-N-phenylthieno[3,2-b]pyridine-3-amine (MU2410))

[1482] [ka]

[1483] To a solution (5-chloro-N-phenylthieno[3,2-b]pyridine-3-amine (Preparation Example 75) (90 mg, 0.345 mmol) dissolved in dioxane (4 mL)), 1-methyl-2-(tributylstanyl)-1H-imidazole (137 μL, 0.414 mmol) and bis(tri-tert-butylphosphine)palladium (0) (14 mg, 0.028 mmol) were added, and the reaction mixture was refluxed for 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, 50:50:0 to 0:95:5 gradient). The product was obtained as a yellow waxy substance (52 mg, 49% yield).

[1484] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.15 (d, J=8.4Hz, 1H), 7.61 (d, J=8.3Hz, 2H), 7.55 (s, 1H), 7.36(t, J=7.8Hz, 2H), 7.25(s, 1H), 7.05(d, J=5.5Hz, 2H), 6.99(t, J=7.3Hz, 1H), 4.13(s, 3H).

[1485] 13C NMR (126MHz, Chloroform-d) δ(ppm) 147.68, 146.67, 142.52, 141.02, 134.73, 131.57, 130.65, 129.91, 129.54, 121.09, 118.36, 116.88, 101.65, 34.76.

[1486] FTIR (NEET), CM -1 :3379, 3108, 2923, 1569, 1530, 1495, 1447, 1393, 1248, 1163, 1122, 1063, 820, 736, 690, 657, 501.

[1487] HRMS (APCI): Theoretical value (C 17 H 15 N4S)[M+H] + =307.1012, measured value [M+H] + = 307.1010.

[1488] (Preparation Example 203: 5-(1-methyl-1H-1,2,3-triazol-4-yl)-N-phenylthieno[3,2-b]pyridine-3-amine (MU2411))

[1489] [ka]

[1490] The compound was prepared according to general procedure C using 5-chloro-N-phenylthieno[3,2-b]pyridine-3-amine (Preparation Example 75) (60 mg, 0.230 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-1,2,3-triazole (58 mg, 0.276 mmol). Reaction time: 3 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 80:20 to 60:40 gradient). The product was obtained as a white solid (63 mg, 90% yield).

[1491] 1H NMR (500MHz, Chloroform-d) δ(ppm)8.29(s, 1H), 8.25(d, J=8.4Hz, 1H), 8.21(d, J=8.4Hz, 1H), 7.37(t t, J=7.3, 1.9Hz, 2H), 7.31(dd, J=8.6, 1.1Hz, 2H), 7.22(s, 1H), 7.04(s, 1H), 6.99(s, 1H), 4.22(s, 3H).

[1492] 13 C NMR (126MHz, Chloroform-d) δ(ppm) 148.65, 146.87, 142.54, 134.47, 131.73, 131.30, 129.48, 123.11, 120.99, 117.00, 116.96, 101.20, 36.88.

[1493] FTIR (NEET), CM -1 :3393, 3115, 3033, 2944, 1589, 1564, 1531, 1497, 1393, 1328, 1226, 1047, 804, 749, 691, 489.

[1494] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + =308.0964, measured value [M+H] + =308.0962.

[1495] (Preparation Example 204: 5-(2-methyl-2H-1,2,3-triazol-4-yl)-N-phenylthieno[3,2-b]pyridine-3-amine (MU2412))

[1496] [ka]

[1497] The compound was prepared according to general procedure B using 5-chloro-N-phenylthieno[3,2-b]pyridine-3-amine (Preparation Example 75) (81 mg, 0.330 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-1,2,3-triazole (58 mg, 0.276 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 100:0 to 80:20 gradient). The product was obtained as a white solid (30 mg, 43% yield).

[1498] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 8.30 (s, 1H), 8.19 (d, J=8.4Hz, 1H), 7.97 (d, J=8 .4Hz, 1H), 7.40~7.34(m, 3H), 7.33(dd, J=8.7, 1.3Hz, 3H), 7.04(s, 1H), 4.30(s, 3H).

[1499] 13 C NMR (126MHz, Chloroform-d) δ(ppm) 147.83, 147.61, 146.27, 142.48, 134.69, 133.16, 131.90, 131.55, 129.46, 121.05, 117.14, 117.08, 101.22, 41.95.

[1500] FTIR (NEET), CM -1 :1602, 1566, 1533, 1387, 1155, 827, 723, 693, 515.

[1501] HRMS (APCI): Theoretical value (C 16 H 14 N5S)[M+H] + =308.0964, measured value [M+H] + =308.0962.

[1502] (Preparation Example 205: (5-((1,4-dimethyl-1H-pyrazole-3-yl)amino)thieno[3,2-b]pyridine-3-yl)(phenyl)methanone (MU2313))

[1503] [ka]

[1504] The compound was prepared according to general procedure C using (5-chlorothieno[3,2-b]pyridine-3-yl)phenylmethanone (Preparation Example 72) (45 mg, 0.141 mmol) and 1,4-dimethyl-1H-pyrazole-3-amine (19 mg, 0.169 mmol). Reaction time: 20 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA / methanol, gradient from 20:80:0 to 0:98:2), TLC for preparation (cyclohexane / siRNA, 70:30, eluted twice, 98:2, eluted once, and 100:0, eluted once), and TLC for reversed phase preparation (methanol, eluted once). The product was obtained as a white solid (6 mg, yield 12%).

[1505] 1 H NMR (500MHz, DMSO-d6) δ (ppm) 8.96 (s, 1H), 8.60 (s, 1H), 8.57 (d, J=5.1Hz, 2H), 8.27 (d, J=8.9Hz) , 2H), 8.22(dd, J=4.7, 1.5Hz, 2H), 7.07(d, J=8.9Hz, 1H), 6.60(s, 1H), 4.07(s, 3H), 2.12(s, 3H).

[1506] 13 C NMR (126MHz, DMSO-d6) δ(ppm) 154.50, 151.02, 149.53, 143.25, 141.17, 135.76, 132.68, 130.76, 130.54, 124.60, 121.62, 107.48, 41.22, 9.76.

[1507] FTIR (NEET), CM -1:2926, 2870, 1651, 1579, 1538, 1481, 1470, 1397, 1311, 1229, 1177, 818, 721, 696, 653, 453.

[1508] HRMS (APCI): Theoretical value (C 19 H 17 N4OS)[M+H] + =349.1118, measured value [M+H] + =349.1121.

[1509] (Preparation Example 206: 3-(2-(aminomethyl)pyridine-4-yl)-N-(1,4-dimethyl-1H-pyrazole-3-yl)thieno[3,2-b]pyridine-5-amine (MU1946))

[1510] [ka]

[1511] The compound was prepared according to general procedure C using tert-butyl((4-(5-chlorothieno[3,2-b]pyridine-3-yl)pyridine-2-yl)methyl)carbamate (Preparation Example 26) (165 mg, 0.439 mmol), triethylamine (184 μL, 1.32 mmol), and 1,4-dimethyl-1H-pyrazole-3-amine (59 mg, 0.527 mmol). Reaction time: 16 hours. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / siRNA, 20:80 to 2:98 gradient). The product was obtained as a pale yellow solid (64 mg, 32% yield).

[1512] 1H NMR (500MHz, Chloroform-d) δ8.58(d, J=5.66Hz, 1H), 8.03(m, 1H), 8.01(d, J=8.94Hz, 1H), 7.93(s, 1H), 7.87(m, 1H), 7.3 7(d, J=8.75Hz, 1H), 7.16(s, 1H), 6.59(s, 1H), 5.65(s, 1H), 4.50(d, J=5.3Hz, 2H), 3.83(s, 3H), 2.00(s, 3H), 1.47(s, 9H).

[1513] 13 ¹³C NMR (126MHz, Chloroform-d) δ157.32, 156.06, 154.82, 151.50, 149.14, 147.25, 142.83, 132.49, 132.32, 129.87, 128.91, 125.63, 124.1~123.77 (rotamer), 121.14~120.55 (rotamer), 107.67, 107.18, 79.35, 45.94, 38.91, 28.44, 7.89.

[1514] FTIR (NEET), CM -1 :3322, 2976, 2925, 1775, 1703, 1602, 1579, 1541, 1483, 1366, 1314, 1248, 1266, 785, 735.

[1515] HRMS (APCI): Theoretical value (C 23 H 27 N6O2S)[M+H] + = 451.1911, measured value [M+H] + = 451.1908.

[1516] (Preparation example 207: 5-chloro-3-(pyrimidine-4-yl)thieno[3,2-b]pyridine)

[1517] [ka]

[1518] To a solution (3-bromo-5-chlorothieno[3,2-b]pyridine (200 mg, 0.804 mmol) dissolved in dioxane (3 mL)), 4-(tributylstanyl)pyrimidine (306 μL, 0.965 mmol) and bis(tri-tert-butylphosphine)palladium (0) (33 mg, 0.064 mmol) were added, and the reaction mixture was refluxed for 2 hours. The solvent was evaporated, and the residue was purified by flash chromatography (hexane / siRNA, 80:20 to 50:50 gradient). The product was obtained as a white solid (116 mg, 58% yield).

[1519] 1 H NMR (500MHz, Chloroform-d) δ (ppm) 9.24 (d, J=1.3Hz, 1H), 8.96 (s, 1H), 8.94 (dd, J= 5.3, 1.4Hz, 1H), 8.88(d, J=5.3Hz, 1H), 8.19(d, J=8.5Hz, 1H), 7.38(d, J=8.5Hz, 1H).

[1520] 13 C NMR (126MHz, Chloroform-d) δ(ppm) 158.65, 158.04, 157.73, 152.47,...

Claims

1. General formula I 【Chemistry 1】 A compound represented by, The pharmaceutically acceptable salt thereof, In general formula I, R ２ H, C1-C4 alkyl, and CF ３ Selected from; Y is selected from bonding, -C(=O)-, -CH(OH)-, -C(=CH ２ ), -, -CH ２ -O-, -CH ２ -S-, -CH ２ -NH ２ -, O, S, SO ２ , NR ８ , or CR ８ R ８ ; and is selected from R ３ teeth, C6-C14 aryl, A 3- to 10-membered heteroaryl compound containing at least one heteroatom selected from S, O, and N. C5-C8 cycloalkyl, A 5- to 8-membered heterocycloalkyl group containing at least one heteroatom selected from S, O, and N. C5-C8 cycloalkenyls, A 5- to 8-membered heterocycloalkenyl containing at least one heteroatom selected from S, O, and N, Selected from the group consisting of, Here, each substituent listed is: C1-C4 alkyl, C6-C10 aryl, 3-7 membered heteroaryl containing at least one heteroatom selected from S, O, N, 3-7 membered heterocycloalkyl containing at least one heteroatom selected from S, O, N, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, halogen, OH, HO-C1-C4 alkyl, O(C1-C4 alkyl), O(C3-C7 cycloalkyl), O(C1-C4 halogen alkyl), (C1-C4 alkyl)-O-C1-C4 alkyl, O(C5-C6 aryl or 5-6 membered heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 halogen alkyl), S(C5-C6 aryl or 5-6 membered heteroaryl), SO(C1-C4 alkyl), SO ２ (C1-C4 alkyl), CF ３ , C ２ F ５ OCF ３ , OC ２ F ５ , amino (NH ２ ), NH ２ -(C1-C4 alkyl)-, HCO-NH-(C1-C4 alkyl)-, NO ２ , CN, N ３ , C1-C4 alkylamino, di(C1-C4 alkyl)amino, (C5-C6 aryl or 5-6 membered heteroaryl)amino, di(C5-C6 aryl or heteroaryl)amino, (C1-C4 alkyl)-NH-C1-C4 alkyl, (C1-C4 alkyl) ２ -N-C1~C4-alkyl,=O,=S,=N-OH,-(C1~C4 alkylene)=N-OH,=N-O(C1~C4 alkyl),-(C1~C4 alkylene)=N-O(C1~C4 alkyl),-(C1~C4 alkyl)-CHO,-CHO,-COOH,-(C1~C4 alkylene)-COOH,-CONH ２ ,-(C1-C4 alkylene)-CONH ２ -COO(C1-C4 alkyl), -(C1-C4 alkylene)-COO(C1-C4 alkyl), -CO(C1-C4 alkyl), -(C1-C4 alkylene)-CO(C1-C4 alkyl), -CO(C5-C6 aryl or 5-6 membered heteroaryl), -(C1-C4 alkylene)-CO(C5-C6 aryl or 5-6 membered heteroaryl), (C1-C4 alkyl)-SO ２ -, (C1-C4 alkyl)-SO ２ -(C1-C4 alkylene)-, (C1-C4 alkyl)-SO-, (C1-C4 alkyl)-SO-(C1-C4 alkylene)-, (C1-C4 alkyl)-SO ２ -NH-, (C1-C4 alkyl)-SO ２ -NH-(C1-C4 alkylene)-,(C1-C4 alkyl)-SO ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl)-SO ２ -N(C1-C4 alkyl)-(C1-C4 alkylene)-, (C1-C4 alkyl)-O-CO-, (C1-C4 alkyl)-O-CO-(C1-C4 alkylene)-, (C1-C4 alkyl)-NH-CO-, (C1-C4 alkyl)-NH-CO-(C1-C4 alkylene)-, (C6-C10 aryl)-NH-CO, (C6-C10 aryl)-NH-CO-(C1-C4 alkylene)-, (C1-C4 alkyl) ２ N-CO-, (C1-C4 alkyl) ２ N-CO-(C1-C4 alkylene)-,NH ２ -SO ２ -, NH ２ -SO ２ -(C1-C4 alkylene)-, (C6-C10 aryl)-NH-SO ２ -, (C6-C10 aryl)-NH-SO ２ -(C1-C4 alkylene)-,(C1-C4 alkyl)-NH-SO ２ -, (C1-C4 alkyl)-NH-SO ２ -(C1-C4 alkylene)-, (C1-C4 alkyl) ２ N-SO ２ -, (C1-C4 alkyl) ２ N-SO ２ -(C1-C4 alkylene)-, (C1-C4 alkyl)-CO-NH-, (C1-C4 alkyl)-CO-NH-(C1-C4 alkylene)-, (C1-C4 alkyl)-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-CO-N(C1-C4 alkyl)-(C1-C4 alkylene)-, (C1-C4 alkyl)-OCO-NH-, (C 1-C4 alkyl)-OCO-NH-(C1-C4 alkylene)-,(C1-C4 alkyl)-OCO-N(C1-C4 alkyl)-,(C1-C4 alkyl)-OCO-N(C1-C4 alkyl)-(C1-C4 alkylene)-,(C1-C4 alkyl)-CO-NH-CO-,(C1-C4 alkyl)-CO-N(C1-C4 alkyl)-CO-,NH ２ -CO-NH-, (C1-C4 alkyl)-NH-CO-NH-, (C1-C4 alkyl) ２ N-CO-NH-, NH ２ -CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl) ２ N-CO-N(C1-C4 alkyl)-,NH ２ -S(O) ２ -NH-, (C1-C4 alkyl)-NH-S(O) ２ -NH-, (C1-C4 alkyl) ２ N-S(O) ２ -NH-, NH ２ -S(O) ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-S(O) ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl) ２ N-S(O) ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl) ２ N-(C1-C4 alkylene)-CO-,(C1-C4 alkyl) ２ N-(C1-C4 alkylene)-SO ２ -, (C1-C4 alkyl) ２ N-(C1-C4 alkylene)-SO ２ -NH-, (C1-C4 alkyl) ２ N-(C1-C4 alkylene)-NH-SO ２ - It may be optionally substituted by at least one substituent independently selected from; X represents the bond, O, S, SO ２ , -C(=O)-, -CH(OH)-, -CH ２ -O-, -CH ２ -S-, -CH ２ -NH ２ -, -C (=CH ２ ) - NR ８ , or CR ８ R ８ Selected from; R ５ teeth, C6-C14 aryl, A 3- to 10-membered heteroaryl compound containing at least one heteroatom selected from S, O, and N. C5-C8 cycloalkyl, A 5- to 8-membered heterocycloalkyl group containing at least one heteroatom selected from S, O, and N. C5-C8 cycloalkenyls, A 5- to 8-membered heterocycloalkenyl containing at least one heteroatom selected from S, O, and N, Selected from the group consisting of, Here, each substituent listed is: C1-C4 alkyl, C6-C10 aryl, 3-7 member heteroaryl containing at least one heteroatom selected from S, O, N, 3-7 member heterocycloalkyl containing at least one heteroatom selected from S, O, N, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, halogen, OH, HO-C1-C4 alkyl, O(C1-C4 alkyl), O(C3-C7 cycloalkyl), O(C1-C4 haloalkyl), (C1-C4 alkyl)-O-C1-C4 alkyl, O(C5-C6 aryl or 5-6 member heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 haloalkyl), S(C5-C6 aryl or 5-6 member heteroaryl), SO(C1-C4 alkyl), SO ２ (C1-C4 alkyl), CF ３ , C ２ F ５ , OCF ３ , OC ２ F ５ , amino (NH ２ ), NH ２ -(C1-C4 alkyl)-, HCO-NH-(C1-C4 alkyl)-, NO ２ , CN, N ３ , C1-C4 alkylamino, di(C1-C4 alkyl)amino, (C5-C6 aryl or 5-6 member heteroaryl)amino, di(C5-C6 aryl or heteroaryl)amino, (C1-C4 alkyl)-NH-C1-C4 alkyl, (C1-C4 alkyl) ２ -N-C1-C4-alkyl, =O, =S, =N-OH, -(C1-C4 alkylene)=N-OH, =N-O(C1-C4 alkyl), -(C1-C4 alkylene)=N-O(C1-C4 alkyl), -(C1-C4 alkylene)-CHO, -CHO, -COOH, -(C1-C4 alkylene)-COOH, -CONH ２ , -(C1-C4 alkylene)-CONH ２ , -COO(C1-C4 alkyl), -(C1-C4 alkylene)-COO(C1-C4 alkyl), -CO(C1-C4 alkyl), -(C1-C4 alkylene)-CO(C1-C4 alkyl), -CO(C5-C6 aryl or 5-6 member heteroaryl), -(C1-C4 alkylene)-CO(C5-C6 aryl or 5-6 member heteroaryl), (C1-C4 alkyl)-SO ２ -, (C1-C4 alkyl)-SO ２ -(C1-C4 alkylene)-, (C1-C4 alkyl)-SO-, (C1-C4 alkyl)-SO-(C1-C4 alkylene)-, (C1-C4 alkyl)-SO ２ -NH-, (C1-C4 alkyl)-SO ２ -NH-(C1-C4 alkylene)-, (C1-C4 alkyl)-SO ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl)-SO ２ -N(C1-C4 alkyl)-(C1-C4 alkylene)-, (C1-C4 alkyl)-O-CO-, (C1-C4 alkyl)-O-CO-(C1-C4 alkylene)-, (C1-C4 alkyl)-NH-CO-, (C1-C4 alkyl)-NH-CO-(C1-C4 alkylene)-, (C6-C10 aryl)-NH-CO, (C6-C10 aryl)-NH-CO-(C1-C4 alkylene)-, (C1-C4 alkyl) ２ N-CO-, (C1-C4 alkyl) ２ N-CO-(C1-C4 alkylene)-, NH ２ -SO ２ -, NH ２ -SO ２ -(C1-C4 alkylene)-, (C6-C10 aryl)-NH-SO ２ -, (C6-C10 aryl)-NH-SO ２ -(C1-C4 alkylene)-, (C1-C4 alkyl)-NH-SO ２ -, (C1-C4 alkyl)-NH-SO ２ -(C1-C4 alkylene)-, (C1-C4 alkyl) ２ N-SO ２ -, (C1-C4 alkyl) ２ N-SO ２ -(C1-C4 alkylene)-, (C1-C4 alkyl)-CO-NH-, (C1-C4 alkyl)-CO-NH-(C1-C4 alkylene)-, (C1-C4 alkyl)-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-CO-N(C1-C4 alkyl)-(C1-C4 alkylene)-, (C1-C4 alkyl)-OCO-NH-, (C 1-C4 alkyl)-OCO-NH-(C1-C4 alkylene)-,(C1-C4 alkyl)-OCO-N(C1-C4 alkyl)-,(C1-C4 alkyl)-OCO-N(C1-C4 alkyl)-(C1-C4 alkylene)-,(C1-C4 alkyl)-CO-NH-CO-,(C1-C4 alkyl)-CO-N(C1-C4 alkyl)-CO-,NH ２ -CO-NH-, (C1-C4 alkyl)-NH-CO-NH-, (C1-C4 alkyl) ２ N-CO-NH-, NH ２ -CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl) ２ N-CO-N(C1-C4 alkyl)-,NH ２ -S(O) ２ -NH-, (C1-C4 alkyl)-NH-S(O) ２ -NH-, (C1-C4 alkyl) ２ N-S(O) ２ -NH-, NH ２ -S(O) ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-S(O) ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl) ２ N-S(O) ２ -N(C1-C4 alkyl)-, (C1-C4 alkyl) ２ N-(C1-C4 alkylene)-CO-,(C1-C4 alkyl) ２ N-(C1-C4 alkylene)-SO ２ -, (C1-C4 alkyl) ２ N-(C1-C4 alkylene)-SO ２ -NH-, (C1-C4 alkyl) ２ N-(C1-C4 alkylene)-NH-SO ２ - It may be optionally substituted by at least one substituent independently selected from; R ６ H, C1-C4 alkyl, and CF ３ Selected from; R ７ H, C1-C4 alkyl, amino(C1-C4) alkyl, F, Cl, Br, OR ８ , and CF ３ Selected from; R ８ These are independently selected from H and C1-C4 alkyl groups. A compound or a pharmaceutically acceptable salt thereof.

2. R ３ but, C6-C10 aryls, and, A 5- to 10-membered heteroaryl compound containing at least one heteroatom selected from S, O, and N. Selected from the group consisting of, Here, the aryl or heteroaryl can be optionally substituted. The compound according to claim 1.

3. R ３ but, Phenyl, and, A 5- to 10-membered heteroaryl comprising at least one heteroatom N and optionally at least one other heteroatom selected from S, O, and N. Selected from the group consisting of, Here, the phenyl or heteroaryl can be optionally substituted. The compound according to claim 1.

4. R ３ but, Selected from the group consisting of pyridinyl, phenyl, naphthyl, thiazolyl, thiadiazolyl, isothiazolyl, pyrimidinyl, pyridadinyl, pyrazolyl, pyrrolopyridinyl, quinazolinyl, quinoxalinyl, indazolyl, triazolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, imidazopyridinyl, dihydropyridinyl, and tetrahydropyridinyl, Here, any of these substituents can be arbitrarily substituted. The compound according to claim 1.

5. R ３ but, Substituted by one or more substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, halogen, CN, morpholinyl, benzyl, hydroxy, amino, aminomethyl, trifluoromethoxy, and trifluoromethyl, The compound according to any one of claims 1 to 4.

6. R ５ but, Selected from the group consisting of 5-10 membered heteroaryls containing at least one heteroatom selected from C6-C10 aryls, S, O, and N, and 5-6 membered heterocycloalkyls containing at least one heteroatom selected from S, O, and N, Here, the aryl, heteroaryl, or heterocycloalkyl is optionally substituted. The compound according to any one of claims 1 to 5.

7. R ５ but, Phenyl, Morpholinil, and, A 5- to 10-membered heteroaryl comprising at least one heteroatom N and optionally at least one other heteroatom selected from S, O, and N. Selected from the group consisting of, Here, the phenyl, morpholinyl, and heteroaryl can be optionally substituted. The compound according to any one of claims 1 to 5.

8. R ５ but, Selected from the group consisting of pyrazolyl, phenyl, morpholinyl, imidazolyl, isothiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyridadinyl, pyrazolopyrimidinyl, furanil, and isoxazolyl, Here, any of these substituents can be arbitrarily substituted. The compound according to any one of claims 1 to 5.

9. R ５ but, Substituted by one or more substituents independently selected from C1-C4 alkyl, trifluoromethyl, benzyl, phenyl, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, amino, halogen, -COO(C1-C4 alkyl), C1-C4 alkylthio, C1-C4 alkoxy, and CN. The compound according to any one of claims 1 to 8.

10. A compound represented by general formula I as described in claim 1, or a pharmaceutically acceptable salt thereof, In general formula I, R ２ is selected from H and C1-C4 alkyl groups; Y is a bond, -C(=O)-, -CH(OH)-, -C(=CH ２ ) -, -CH ２ -O-, -CH ２ -S-, -CH ２ -NH ２ -, O, S, NH, N(CH ３ ), or CH ２ Selected from; R ３ teeth, Phenyl, Naphthyl, and, A 5- to 10-membered heteroaryl comprising at least one heteroatom N and optionally at least one other heteroatom selected from S, O, and N. Selected from the group consisting of, Here, the phenyl, naphthyl, or heteroaryl is Either it is not replaced, or Substituted with one or more substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, halogen, CN, morpholinyl, benzyl, hydroxy, amino, aminomethyl, trifluoromethoxy, and trifluoromethyl; X represents the bonds: O, S, -C(=O)-, -CH(OH)-, -CH ２ -O-, -CH ２ -S-, -CH ２ -NH ２ -, -C (=CH ２ )-, NH, N(CH ３ ), or CH ２ Selected from; R ５ teeth, Selected from the group consisting of 5-10 membered heteroaryls containing at least one heteroatom selected from C6-C10 aryls, S, O, and N, and 5-6 membered heterocycloalkyls containing at least one heteroatom selected from S, O, and N, Here, the aryl, heteroaryl, or heterocycloalkyl is Either it is not replaced, or Substituted by one or more substituents independently selected from C1-C4 alkyl, trifluoromethyl, benzyl, phenyl, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, amino, halogen, -COO(C1-C4 alkyl), C1-C4 alkylthio, C1-C4 alkoxy, and CN; R ６ is selected from H and C1-C4 alkyl groups; R ７ H, C1-C4 alkyl, NH ２ CH ２ F, Cl, Br, OH, and OCH ３ Selected from, A compound or a pharmaceutically acceptable salt thereof.

11. A compound represented by general formula I as described in claim 1, or a pharmaceutically acceptable salt thereof, In general formula I, R ２ is selected from H and C1-C4 alkyl groups; Y is a bond, -C(=O)-, -CH(OH)-, -C(=CH ２ ) -, -CH ２ -O-, -CH ２ -S-, -CH ２ -NH ２ -, O, S, NH, N(CH ３ ), or CH ２ Selected from; R ３ teeth, Selected from the group consisting of pyridinyl, phenyl, naphthyl, thiazolyl, thiadiazolyl, isothiazolyl, pyrimidinyl, pyridadinyl, pyrazolyl, pyrrolopyridinyl, quinazolinyl, quinoxalinyl, indazolyl, triazolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, pyrazolopyridinyl, imidazopyridinyl, dihydropyridinyl, and tetrahydropyridinyl, Here, all of these substituents are Either it is not replaced, or Substituted with one or more substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, halogen, CN, morpholinyl, benzyl, hydroxy, amino, aminomethyl, trifluoromethoxy, and trifluoromethyl; X represents the bonds: O, S, -C(=O)-, -CH(OH)-, -CH ２ -O-, -CH ２ -S-, -CH ２ -NH ２ -, -C (=CH ２ )-, NH, N(CH ３ ), or CH ２ Selected from; R ５ teeth, Selected from the group consisting of pyrazolyl, phenyl, morpholinyl, imidazolyl, isothiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyridadinyl, pyrazolopyrimidinyl, furanil, and isoxazolyl, Here, all of these substituents are Either it is not replaced, or Substituted by one or more substituents independently selected from C1-C4 alkyl, trifluoromethyl, benzyl, phenyl, cyclo(C3-C6 alkyl), cyclo(C3-C6 alkyl)-C1-C2 alkyl-, amino, halogen, -COO(C1-C4 alkyl), C1-C4 alkylthio, C1-C4 alkoxy, and CN; R ６ is selected from H and C1-C4 alkyl groups; R ７ H, C1-C4 alkyl, NH ２ CH ２ F, Cl, Br, OH, and OCH ３ Selected from, A compound or a pharmaceutically acceptable salt thereof. 【Request Item 12】 【Chemistry 2】 【change】 And, The pharmaceutically acceptable salt, A compound according to any one of claims 1 to 11, selected from the above.

13. A compound represented by formula I according to any one of claims 1 to 12, for use as a pharmaceutical.

14. A compound represented by formula I according to any one of claims 1 to 12, for use in the treatment of diseases involving CDKL, CLK, DYRK, Haspin, PIM, TAF1L, and / or TRB kinase.

15. A compound represented by formula I according to any one of claims 1 to 12, for use in the treatment of cancer or neurodegenerative diseases.

16. A compound represented by formula I according to any one of claims 1 to 12, for use in the treatment of leukemia (such as acute myeloid leukemia); autoimmune diseases (such as rheumatoid arthritis or autoimmune hepatitis); peripheral neuropathic pain; cancer (such as non-small cell lung cancer (NSCLC), ovarian cancer, glioblastoma, breast cancer, lung cancer, lung adenocarcinoma, pancreatic cancer, prostate cancer, brain tumor, ovarian cancer, colorectal cancer, liver cancer, hepatocellular carcinoma, squamous cell carcinoma, etc.); periodontitis; pulmonary fibrosis; obesity; insulin resistance; obesity-induced hyperinsulinemia; arteriosclerosis; and neurodegenerative disorders (such as Alzheimer's disease).

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