Substituted furopyridines for therapeutic use

Abstract

The present invention relates to furo-pyridine compounds of formula I: # imgabs0 for use in the treatment of FLT3-related diseases, DDR-related diseases, and MAP4K-related diseases.

Description

Technical Field

[0001] The present invention relates to novel heterocyclic compounds that can be used for therapeutic purposes based on the inhibition of FLT3, DDR1, and KHS / MAP4K5 kinases. Background Art

[0002] Protein kinase-mediated protein phosphorylation is important for the activation and inactivation of many signaling pathways in cells.

[0003] FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is expressed almost exclusively in the hematopoietic compartment. Its ligand, FLT3 ligand (FL), induces dimerization and activates its intrinsic tyrosine kinase activity. Activation of FLT3 leads to its autophosphorylation and initiation of several signal transduction cascades. Activation of FLT3 mediates cell survival, cell proliferation, and differentiation of hematopoietic progenitor cells (Physiological Reviews 2019, 99, 1433). In particular, inhibition of FLT3 has been recognized as an attractive strategy for the treatment of acute myeloid leukemia, and many FLT3 inhibitors have been analyzed clinically (Leukemia 2019, 33, 299). Overactivity of FLT3 is also associated with autoimmune diseases such as rheumatoid arthritis or autoimmune hepatitis (Hepatology Forum 2021, 2, 112); and its inhibition has been proposed as a treatment method (Proceedings of the National Academy of Sciences of the United States of America 2005, 102, 16741). In addition, inhibition of FLT3 can be used to treat peripheral neuropathic pain (Nature Communications 2018, 9:1042).

[0004] Discoidin domain receptor (DDR) kinases play a crucial role in regulating fundamental cellular processes such as morphogenesis, differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. Dysregulation of DDR has been attributed to various human cancer diseases such as non-small cell lung cancer (NSCLC), ovarian cancer, glioblastoma, and breast cancer. A large number of studies have shown that elevated DDR expression levels and / or mutations can be found in many cancer cell lines as well as primary tumor tissues (such as in the lung, pancreas, prostate, breast, brain, ovary, and liver) (International Journal of Molecular Sciences 2021, 22, 6535 and references therein). DDR1 has been found to be a prognostic marker in patients with non-small cell lung cancer (NSCLC). Analysis of the clinicopathological parameters of NSCLC patients has shown a significant association between DDR1 overexpression and lymph node metastasis (British Journal of Cancer 2007, 96, 808). In addition, overexpression of DDR1 is associated with collective cell invasion, which is a common pathological feature in many cancer types and may be a key step in cancer metastasis. Specifically, it has been demonstrated that in a mouse model of oral squamous cell carcinoma, lymphovascular invasion can be inhibited by in vivo pharmacological inhibition, indicating that DDR1 inhibitors can be used to treat oral cancer (Cancers 2020, 12, 841).

[0005] In addition, DDR dysregulation can be associated with some inflammatory and neurodegenerative diseases. Along this line of thought, recent studies have shown that inhibiting DDR has therapeutic potential for the treatment of periodontitis (Journal of Cellular Physiology 2022, 237, 189) and pulmonary fibrosis (Acta Pharmacologica Sinica 2022, 43, 1769 and Acta Pharmaceutica Sinica B 2022, 12, 1943). Accordingly, a great deal of work has been invested in the development of DDR inhibitors (Biomolecules 2021, 11, 1671).

[0006] MAP kinases (MAP4K) belong to the mammalian Ste20-like serine / threonine kinase family. MAP4K includes MAP4K1 / HPK1, MAP4K2 / GCK, MAP4K3 / GLK, MAP4K4 / HGK, MAP4K5 / KHS, and MAP4K6 / MINK, and plays diverse roles in immune cell signaling, immune responses, and inflammation (Advances in Immunology 2016, 129, 277). MAP4K is directly associated with many different diseases, including obesity (Molecular and Cellular Biology 2015, 35, 2356), insulin resistance (ACS Medicinal Chemistry Letters 2015, 6, 1128 and Journal of Biological Chemistry 2007, 282, 7783), and obesity-induced hyperinsulinemia (Journal of Biological Chemistry 2016, 291, 16221), and atherosclerosis (Trends in Endocrinology & Metabolism 2016, 27, 484).

[0007] Aberrant expression / splicing of these kinases is also involved in the transformation and metastasis processes in hepatocellular carcinoma (World Journal of Gastroenterology 2010, 16, 4541), lung adenocarcinoma (Pathology–Research and Practice 2012, 208, 541), colorectal cancer (Biochimica et Biophysica Acta–Molecular Cell Research 2018, 1865, 259), and other human tumor cells (Molecular and Cellular Biology 2003, 23, 2068).

[0008] Inhibition of MAP4K can trigger neuroprotective and anti-inflammatory effects, which can potentially be used to treat Alzheimer's disease and other neurodegenerative diseases (Cell Chemical Biology 2019, 26, 1703).

[0009] KHS / MAP4K5 plays an important role particularly in regulating a series of cellular responses; targeting impaired KHS / MAP4K5 signaling has been proposed as a new therapeutic strategy for pancreatic cancer (PLoS ONE 2016, 11(3): e0152300). It has been found that dual inhibition of kinases TAOK1 and KHS / MAP4K5 results in potent inhibition of colorectal and lung cancer cell lines (Journal of Enzyme Inhibition and Medicinal Chemistry 2021, 36, 98). In addition, the compound AZD4547 targeting MAP4K3, MAP4K5, IRR, RET, and FLT3 exhibits anticancer properties (Molecular Cancer Therapeutics 2015, 14, 2292).

[0010] The furanopyridine moiety has not been used to inhibit MAPK or DDR. 3,5-Disubstituted furano[3,2-b]pyridines have been reported as moderately potent inhibitors of the kinase FLT3 (WO 2015 / 165428 A1). SUMMARY OF THE INVENTION

[0011] The present invention relates to compounds of general formula I or pharmaceutically acceptable salts thereof

[0012]

[0013] wherein:

[0014] R 2 is selected from H, C1-C4 alkyl, CF3, C5-C7 cycloalkyl, phenyl, and pyridyl;

[0015] Y is selected from a bond, O, S, SO2, -C≡C-, NR 8 and CR 8 R 8 ;

[0016] R 3 is selected from the group consisting of:

[0017] -C6-C14 aryl,

[0018] - a 3- to 10-membered heteroaryl containing at least one heteroatom selected from S, O, N; provided that the heteroaryl is not an unsubstituted quinoline or an unsubstituted isoquinoline;

[0019] Wherein, each of the listed substituents may optionally be substituted by at least one substituent independently selected from the following: C1-C4 alkyl, C6-C10 aryl, 3- to 7-membered heteroaryl containing at least one heteroatom selected from S, O, N, 3- to 7-membered cycloheteroalkyl containing at least one heteroatom selected from S, O, N, 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- to 6-membered heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 haloalkyl), S(C5-C6 aryl or 5- to 6-membered 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- to 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 alkylene)-CHO, -CHO, -COOH, -(C1-C4 alkylene)-COOH, -CONH2, -(C1-C4 alkylene)-CONH2, -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- to 6-membered heteroaryl), -(C1-C4 alkylene)-CO(C5-C6 aryl or 5- to 6-membered heteroaryl), (C1-C4 alkyl)-SO2-, (C1-C4 alkyl)-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-SO-, (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 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)2N-CO-, (C1-C4 alkyl)2N-CO-(C1-C4 alkylene)-, NH2-SO2-, NH2-SO2-(C1-C4-alkylene)-, (C6-C10 aryl)-NH-SO2-, (C6-C10 aryl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-NH-SO2-, (C1-C4 alkyl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)2N-SO2-, (C1-C4 alkyl)2N-SO2-(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-, (C1-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-, NH2-CO-NH-, (C1-C4 alkyl)-NH-CO-NH-, (C1-C4 alkyl)2N-CO-NH-, NH2-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)2N-CO-N(C1-C4 alkyl)-, NH2-S(O)2-NH-, (C1-C4 alkyl)-NH-S(O)2-NH-, (C1-C4 alkyl)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-;

[0020] Z is selected from a bond, O, S, SO2, NR 8 and CR 8 R 8 ;

[0021] R 6 is selected from the group consisting of:

[0022] -C6-C14 aryl,

[0023] -3- to 10-membered heteroaryl containing at least one heteroatom selected from S, O, N;

[0024] -C3-C8 cycloalkyl, preferably C4-C7 cycloalkyl,

[0025] -3- to 8-membered cycloheteroalkyl containing 1 to 2 heteroatoms selected from S, O, N,

[0026] -C3-C8 cycloalkenyl,

[0027] -3- to 8-membered cycloheteroalkenyl containing 1 to 2 heteroatoms selected from S, O, N,

[0028] -(C3-C8) cycloalkyl-(C6-C14) aryl,

[0029] -(3- to 8-membered) cycloheteroalkyl-(C6-C14) aryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0030] -(C3-C8) cycloalkenyl-(C6-C14) aryl,

[0031] -(3- to 8-membered) cycloheteroalkenyl-(C6-C14) aryl, wherein said cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N,

[0032] -(C3-C8) cycloalkyl-(3- to 10-membered) heteroaryl, wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0033] -(3- to 8-membered) cycloheteroalkyl-(3- to 10-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0034] -(C3-C8) cycloalkenyl-(3- to 10-membered) heteroaryl, wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0035] -(3- to 8-membered) cycloheteroalkenyl-(3- to 10-membered) heteroaryl, wherein said cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0036] -(C3-C8) cycloalkyl-(C1-C4) alkyl-(C6-C14) aryl,

[0037] -(3 to 8-membered) cycloheteroalkyl-(C1-C4)alkyl-(C6-C14)aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0038] -(C3-C8) cycloalkenyl-(C1-C4)alkyl-(C6-C14)aryl,

[0039] -(3 to 8-membered) cycloheteroalkenyl-(C1-C4)alkyl-(C6-C14)aryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N,

[0040] -(C3-C8) cycloalkyl-(C1-C4)alkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0041] -(3 to 8-membered) cycloheteroalkyl-(C1-C4)alkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0042] -(C3-C8) cycloalkenyl-(C1-C4)alkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0043] -(3 to 8-membered) cycloheteroalkenyl-(C1-C4)alkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0044] -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(C6-C14)aryl,

[0045] -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(C6-C14)aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0046] -(C3-C8) cycloalkenyl-(1 to 4-membered) heteroalkyl-(C6-C14)aryl,

[0047] -(3 to 8-membered) cycloheteroalkenyl-(1 to 4-membered) heteroalkyl-(C6-C14)aryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N,

[0048] -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0049] -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0050] -(C3-C8) cycloalkenyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0051] -(3 to 8-membered) cycloheteroalkenyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein said cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0052] -(5 to 10-membered) heteroalkyl-C6-C14 aryl, wherein said heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0053] -(5 to 10-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein said heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0054] Wherein, each of the listed substituents may be unsubstituted or substituted by at least one substituent independently selected from the following: C1-C4 alkyl, C6-C10 aryl, 3- to 7-membered heteroaryl containing at least one heteroatom selected from S, O, N, 3- to 7-membered cycloheteroalkyl containing at least one heteroatom selected from S, O, N, 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- to 6-membered heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 haloalkyl), S(C5-C6 aryl or 5- to 6-membered 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- to 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 alkylene)-CHO, -CHO, -COOH, -(C1-C4 alkylene)-COOH, -CONH2, -(C1-C4 alkylene)-CONH2, -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- to 6-membered heteroaryl), -(C1-C4 alkylene)-CO(C5-C6 aryl or 5- to 6-membered heteroaryl), (C1-C4 alkyl)-SO2-, (C1-C4 alkyl)-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-SO-, (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 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)2N-CO-, (C1-C4 alkyl)2N-CO-(C1-C4 alkylene)-, NH2-SO2-, NH2-SO2-(C1-C4-alkylene)-, (C6-C10 aryl)-NH-SO2-, (C6-C10 aryl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-NH-SO2-, (C1-C4 alkyl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)2N-SO2-, (C1-C4 alkyl)2N-SO2-(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-, (C1-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-, NH2-CO-NH-, (C1-C4 alkyl)-NH-CO-NH-, (C1-C4 alkyl)2N-CO-NH-, NH2-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)2N-CO-N(C1-C4 alkyl)-, NH2-S(O)2-NH-, (C1-C4 alkyl)-NH-S(O)2-NH-, (C1-C4 alkyl)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-;

[0055] R 7 is selected from H, C1-C4 alkyl, and CF3;

[0056] R 8 is independently selected from H and C1-C4 alkyl.

[0057] The compound of formula I can be in the form of the free base or in the form of an addition salt with a pharmaceutically acceptable organic or inorganic acid (such as hydrochloric acid).

[0058] Halogen is selected from fluorine, chlorine, bromine and iodine.

[0059] Alkyl is a branched or linear saturated hydrocarbon group.

[0060] Alkenyl is a branched or linear hydrocarbon group containing at least one double bond.

[0061] Alkylene is a divalent branched or linear, preferably linear, hydrocarbon residue. Preferred alkylene is methylene.

[0062] Cycloalkyl is a saturated hydrocarbon group containing at least one aliphatic ring.

[0063] Cycloalkenyl is a hydrocarbon group containing at least one aliphatic ring and at least one double bond in the ring.

[0064] Aryl is a hydrocarbon group containing at least one aromatic ring. Examples of aryl are phenyl, benzyl.

[0065] Heteroaryl is a hetero-hydrocarbon group containing at least one aromatic ring, the aromatic ring containing at least one heteroatom selected from O, S, N.

[0066] Heterocyclic group or cycloheteroalkyl is a hetero-hydrocarbon group containing at least one aliphatic ring, the aliphatic ring containing at least one heteroatom selected from O, S, N in the ring.

[0067] Cycloheteroalkenyl is a hetero-hydrocarbon group containing at least one double bond and at least one aliphatic ring, the aliphatic ring containing at least one heteroatom selected from O, S, N in the ring.

[0068] Thus, the cyclic structure can contain one or more rings, wherein these rings can be conjugated or connected by a C1-C3 linker.

[0069] Preferably, R 2 is selected from H, methyl, ethyl, propyl and isopropyl. More preferably, R 2 is selected from H and methyl.

[0070] Preferably, Y is selected from a bond, NR 8 or CR 8 R 8 . More preferably, Y is selected from a bond, NH and CH2. Even more preferably, Y is a bond.

[0071] R 3Preferably selected from phenyl and 5- to 6-membered heteroaryl containing one or two heteroatoms selected from N, O, S; wherein the phenyl or 5- to 6-membered heteroaryl is unsubstituted or substituted as defined above for R 3 and is so substituted.

[0072] Preferably, Z is selected from a bond, NR 8 or CR 8 R 8 . More preferably, Z is selected from a bond, NH and CH2. Even more preferably, Z is a bond.

[0073] R 6 is preferably selected from the group consisting of

[0074] -C6-C14 aryl,

[0075] - 3- to 10-membered heteroaryl containing at least one heteroatom selected from S, O, N,

[0076] -(C3-C8) cycloalkyl-(C6-C14) aryl,

[0077] -(3- to 8-membered) cycloheteroalkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0078] -(C3-C8) cycloalkyl-(3- to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0079] -(3- to 8-membered) cycloheteroalkyl-(3- to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0080] -(C3-C8) cycloalkyl-(C1-C4) alkyl-(C6-C14) aryl,

[0081] -(3- to 8-membered) cycloheteroalkyl-(C1-C4) alkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0082] -(C3-C8) cycloalkyl-(C1-C4) alkyl-(3- to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0083] -(3- to 8-membered) cycloheteroalkyl-(C1-C4) alkyl-(3- to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0084] -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl,

[0085] -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0086] -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0087] -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0088] -(5 to 10-membered) heteroalkyl-C6-C14 aryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0089] -(5 to 10-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0090] wherein each of the listed substituents may be unsubstituted or substituted.

[0091] More preferably, R 6 is selected from the group consisting of:

[0092] -phenyl,

[0093] -a 5 to 6-membered heteroaryl containing at least one heteroatom selected from S, O, N,

[0094] -(6-membered) cycloheteroalkyl-phenyl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0095] -(6-membered) cycloheteroalkyl-(5 to 6-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N,

[0096] -(6-membered) cycloheteroalkyl-(C1-C4) alkyl-phenyl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0097] -(6-membered) cycloheteroalkyl-(C1-C4)alkyl-(5- to 6-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0098] -(6-membered) cycloheteroalkyl-(1- to 4-membered) heteroalkyl-phenyl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0099] -(6-membered) cycloheteroalkyl-(1- to 4-membered) heteroalkyl-(5- to 6-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0100] -(5- to 10-membered) heteroalkyl-phenyl, wherein said heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N,

[0101] -(5- to 10-membered) heteroalkyl-(5- to 6-membered) heteroaryl, wherein said heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0102] wherein each of the listed substituents may be unsubstituted or substituted.

[0103] In some embodiments, R 6 is selected from the group consisting of:

[0104] -phenyl,

[0105] -a 5- to 6-membered heteroaryl containing at least one heteroatom selected from S, O, N,

[0106] -(6-membered) cycloheteroalkyl-phenyl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O, N and is bonded to the phenyl through an N atom,

[0107] -(6-membered) cycloheteroalkyl-(5- to 6-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O, N and is bonded to the heteroaryl through an N atom, and wherein said heteroaryl contains at least one heteroatom selected from S, O, N,

[0108] -(6-membered) cycloheteroalkyl-(C1-C4)alkyl-phenyl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O, N and is bonded to the alkyl through an N atom,

[0109] -(6-membered) cycloheteroalkyl-(C1-C4)alkyl-(5- to 6-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the alkyl through an N atom, and wherein said heteroaryl contains at least one heteroatom selected from S, O, and N,

[0110] -(6-membered) cycloheteroalkyl-(1- to 4-membered) heteroalkyl-phenyl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the heteroalkyl through an N atom,

[0111] -(6-membered) cycloheteroalkyl-(1- to 4-membered) heteroalkyl-(5- to 6-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the heteroalkyl through an N atom, and wherein said heteroaryl contains at least one heteroatom selected from S, O, and N,

[0112] -(5- to 10-membered) heteroalkyl-phenyl, wherein said heteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the phenyl through an N atom,

[0113] -(5- to 10-membered) heteroalkyl-(5- to 6-membered) heteroaryl, wherein said heteroalkyl contains 1 to 2 heteroatoms selected from S, O, and N, and wherein said heteroaryl contains at least one heteroatom selected from O and N and is bonded to the heteroalkyl through an N atom,

[0114] wherein each of the listed substituents may be unsubstituted or substituted.

[0115] In some embodiments, R 6 is selected from the group consisting of:

[0116] -phenyl,

[0117] -a 5- to 6-membered heteroaryl containing at least one heteroatom selected from S, O, and N,

[0118] -(6-membered) cycloheteroalkyl-phenyl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the phenyl through an N atom,

[0119] -(6-membered) cycloheteroalkyl-(5- to 6-membered) heteroaryl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the heteroaryl through an N atom, and wherein said heteroaryl contains at least one heteroatom selected from S, O, and N,

[0120] -(6-membered) cycloheteroalkyl-(1- to 4-membered) heteroalkyl-phenyl, wherein said cycloheteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the heteroalkyl through an N atom,

[0121] -(6-membered) cycloheteroalkyl-(1- to 4-membered) heteroalkyl-(5- to 6-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the heteroalkyl through an N atom, and wherein the heteroaryl contains at least one heteroatom selected from S, O, and N,

[0122] -(5- to 10-membered) heteroalkyl-phenyl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the phenyl through an N atom,

[0123] -(5- to 10-membered) heteroalkyl-(5- to 6-membered) heteroaryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, and N, and wherein the heteroaryl contains at least one heteroatom selected from O and N and is bonded to the heteroalkyl through an N atom,

[0124] wherein each of the listed substituents may be unsubstituted or substituted.

[0125] In some embodiments, the heteroaryl moiety in R 6 is pyridyl, which may be unsubstituted or substituted.

[0126] In some embodiments, the cycloheteroalkyl moiety in R 6 is selected from piperidyl, piperazinyl, and morpholinyl, and each of the piperidyl, piperazinyl, and morpholinyl may be unsubstituted or substituted.

[0127] In some embodiments, the 5- to 10-membered heteroalkyl moiety in R 6 contains 1 or 2 nitrogen atoms.

[0128] R 6 The substituents listed may be unsubstituted or further substituted by at least one substituent, preferably by one substituent. The at least one substituent is preferably independently selected from C1-C4 alkyl, halogen, OH, HO-C1-C4 alkyl, O(C1-C4 alkyl), O(C5-C6 aryl or heteroaryl), SH, S(C1-C4 alkyl), S(C5-C6 aryl or heteroaryl), CF3, C2F5, OCF3, OC2F5, amino (NH2), C1-C4 alkylamino, di(C1-C4 alkyl)amino. More preferably, the at least one substituent is selected from C1-C4 alkyl.

[0129] Preferably, R 7 is selected from H, methyl, ethyl, propyl, and isopropyl. More preferably, R 7 is selected from H and methyl.

[0130] In another aspect, the present invention provides the use of the compound of formula I as a drug.

[0131] In particular, the compounds of formula I are suitable for treating FLT3-related diseases, DDR-related diseases and MAP4K-related diseases.

[0132] More specifically, the compounds of Formula I are suitable for treating leukemias, such as acute myeloid leukemia; autoimmune diseases, such as rheumatoid arthritis, autoimmune hepatitis, peripheral neuropathic pain; cancers, such as non-small cell lung cancer (NSCLC), ovarian cancer, glioblastoma, breast cancer, lung cancer, lung adenocarcinoma, pancreatic cancer, prostate cancer, brain cancer, colorectal cancer, liver cancer, hepatocellular carcinoma, squamous cell carcinoma; periodontitis; pulmonary fibrosis; obesity; insulin resistance; obesity-induced hyperinsulinemia; atherosclerosis; neurodegenerative diseases, such as Alzheimer's disease.

[0133] The present invention also includes a pharmaceutical formulation comprising at least one compound of formula I as defined herein and at least one pharmaceutically acceptable excipient selected from pharmaceutically acceptable solvents, fillers and binders. DETAILED DESCRIPTION

[0134] Example

[0135] I. Preparation Examples

[0136] Materials and methods

[0137] All commercially available reagents were used as received without further purification. Reaction solvents were purchased anhydrous and stored under nitrogen. Unless otherwise stated, reactions were performed in oven-dried glassware under nitrogen atmosphere. Column chromatography used silica gel (pore size 230 mesh to 400 mesh particle size, 40 μm to 63 μm particle size). Plates from Merck (PLC silica gel 60F 254 , 1 mm) by preparative thin layer chromatography. 18 -Reversed phase silica gel (pore size Reverse phase column chromatography was performed with 230 mesh to 400 mesh particle size, 40 μm to 63 μm particle size). NMR spectra were obtained in the specified deuterated solvents; chemical shifts are expressed in parts per million (δ) with reference to the appropriate deuterated solvent used. Multiplicity is expressed as s (singlet), d (doublet), t (triplet), q (quartet), p (quintet), quin (quintet), sept (septet), m (multiplet), or (br) broad, or a combination thereof. Coupling constant values are given in Hz.

[0138] General Procedure A

[0139] General procedure A for the Suzuki cross-coupling of 3-bromo-6-chlorofuro[3,2-b]pyridine at the 3-position.

[0140]

[0141] Pd(dppf)Cl2 (0.013 mmol) was added to a degassed solution of 3-bromo-6-chlorofuro[3,2-b]pyridine (0.43 mmol), K3PO4 (1.29 mmol), and boric acid or ester (0.56 mmol) in a mixture of 1,4-dioxane / H2O (4:1; 1.25 mL / 0.1 mmol 3-bromo-6-chlorofuro[3,2-b]pyridine), and the reaction mixture was stirred at 90 °C; the progress of the reaction was followed by TLC. After consumption of the starting material, the mixture was cooled to 25 °C, diluted with H2O (10 mL), and extracted with EtOAc (3 × 15 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography.

[0142] General procedure B for the Suzuki cross-coupling of 6-chloro-3-substituted furo[3,2-b]pyridine at the 6-position.

[0143]

[0144] SPhos Pd G3 (0.007 mmol) was added to a degassed solution of 6-chloro-3-substituted furo[3,2-b]pyridine (0.229 mmol), K3PO4 (0.687 mmol), and boric acid or ester (0.298 mmol) in a mixture of n-BuOH / H2O (4:1; 1.25 mL / 0.1 mmol 6-chloro-3-substituted furo[3,2-b]pyridine), and the reaction mixture was stirred at 110 °C (the progress of the reaction was followed by TLC). After consumption of the starting material, the mixture was cooled to 25 °C, diluted with H2O (10 mL), and extracted with EtOAc (3 × 15 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography.

[0145] General procedure C for the deprotection of N-Boc protected compounds

[0146] HCl (35% aqueous solution, 2 mL, 25.5 mmol) was added to a solution of the corresponding N-Boc-protected compound (0.186 mmol) in MeOH (2 mL), and the reaction mixture was stirred at 50 °C (the progress of the reaction was followed by TLC). After the specified reaction time, the mixture was cooled to 25 °C. The pH was adjusted to 8 with 2 M NaOH (aqueous solution, 13 mL), and the resulting solution was extracted with EtOAc (3 × 30 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography.

[0147] General procedure D for the deprotection of N-Boc protected compounds

[0148] HCl (35% aqueous solution, 2.0 mL) was added to a solution of the corresponding N-Boc protected compound in MeOH (2.0 mL), and the resulting mixture was stirred at 50 °C (the progress of the reaction was monitored by TLC). After the specified specific reaction time, the mixture was evaporated in vacuo. A mixture of DCM / 7M NH3 in MeOH solution (5.0 mL) and NaHCO3 (1.0 g, 11.0 mmol) was added; the mixture was stirred at ambient temperature for 1 hour and used directly for flash chromatography.

[0149] Preparation Example 1: 5-Chloro-2-iodopyridin-3-ol

[0150]

[0151] H2O (80 mL) was added to a mixture of 5-chloropyridin-3-ol (5.12 g, 39.7 mmol), iodine (10.1 g, 39.7 mol), and Na2CO3 (8.83 g, 83.3 mmol), and the resulting mixture was stirred at 25 °C for 3.5 hours under N2. The mixture was neutralized with 1 M aqueous HCl (120 mL) and extracted with EtOAc (120 mL + 70 mL + 70 mL). The combined organic extracts were washed with brine (80 mL), dried over MgSO4, filtered, and the solvent was evaporated. A brown solid product (10.1 g; 100% yield) was obtained.

[0152] 1 1H NMR (300 MHz, DMSO-d6) δ 11.38 (s, 1H), 7.95 (d, J = 2.3 Hz, 1H), 7.17 (d, J = 2.3 Hz, 1H).

[0153] 13 13C NMR (126 MHz, DMSO) δ 154.56, 139.48, 130.81, 120.44, 108.53.

[0154] FTIR (neat), cm -1 : 2843, 2720, 2568, 1744, 1686, 1548, 1411, 1323, 1278, 1241, 1181, 1160, 1113, 1043, 865, 717, 590, 559, 537, 445.

[0155] HRMS (APCI): Calcd for C5H3ClINO [M + H] + = 255.9021, Found [M + H] += 255.9020.

[0156] Preparation Example 2: 6-Chloro-2-(trimethylsilyl)furo[3,2-b]pyridine

[0157]

[0158] To a degassed solution of 5-chloro-2-iodopyridin-3-ol (Preparation Example 1; 5.60 g, 21.9 mmol) in dioxane (30 mL) and TEA (30 mL) was added ethynyltrimethylsilane (4.03 mL, 28.5 mmol), PdCl2(PPh3)2 (461 mg, 0.651 mmol), and CuI (250 mg, 1.31 mmol), and the resulting mixture was stirred at 45 °C for 105 minutes. The solvent was evaporated, and the residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 15:1 to 10:1). An orange solid product (3.59 g, 73% yield) was obtained.

[0159] 1 1H NMR (500 MHz, chloroform-d) δ 8.52 (dd, J = 1.9, 1.4 Hz, 1H), 7.81 - 7.76 (m, 1H), 7.16 - 7.12 (m, 1H), 0.40 (d, J = 1.0 Hz, 9H).

[0160] 13 13C NMR (126 MHz, chloroform-d) δ 170.30, 150.58, 146.96, 144.91, 127.25, 118.30, 117.11, -1.92.

[0161] FTIR (neat), cm -1 : 2958, 2918, 2851, 1453, 1381, 1250, 1043, 935, 839, 756, 635, 601.

[0162] HRMS (APCI): Calcd for C 10 H 12 ClNOSi [M + H] + = 226.0449, found [M + H] + = 226.0458.

[0163] Preparation Example 3: 6-Chlorofuro[3,2-b]pyridine

[0164]

[0165] To a solution of 6-chloro-2-(trimethylsilyl)furo[3,2-b]pyridine (Preparation Example 2; 3.59 g, 15.9 mmol) in methanol (25 mL) was added KF (2.77 mg, 47.7 mmol), and the resulting mixture was stirred at 38 °C for 17 h. The solvent was evaporated in vacuo, and the residue was purified by column chromatography (cyclohexane / EtOAc, gradient 10:1 to 10:3). A white solid product (2.18 g, 89%) was obtained.

[0166] 1 H NMR (500 MHz, chloroform-d) δ 8.58 (s, 1H), 7.85 (d, J = 2.3 Hz, 1H), 7.83 - 7.78 (m, 1H), 7.03 - 6.96 (m, 1H).

[0167] 13 C NMR (126 MHz, chloroform-d) δ 149.87, 146.12, 145.39 - 145.20 (m), 118.66, 108.38.

[0168] FTIR (neat), cm -1 : 3342, 2973, 2926, 1379, 1269, 1087, 1045, 879, 736.

[0169] HRMS (APCI): calcd for C7H4ClNO [M+H] + = 154.0054, found = 154.0058.

[0170] Preparation Example 4: 2,3-Dibromo-6-chloro-2,3-dihydrofuro[3,2-b]pyridine

[0171]

[0172] 6-Chlorofuro[3,2-b]pyridine (Preparation Example 3; 1.0 g, 6.51 mmol) and DCM (25 mL) were placed in a 100 mL round-bottom flask. Bromine (1.0 mL, 19.5 mmol) was added slowly. The mixture was stirred at 25 °C for 3 h. Then, a Na2S2O3 solution (15 mL, 20% aqueous solution containing 2% Na2CO3) was added, and the resulting mixture was extracted with DCM (3 x 30 mL). The organic matter was collected, dried over MgSO4, filtered, and the solvent was evaporated in vacuo (while maintaining the bath temperature at 30 °C).

[0173] The crude material was purified by flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 5:1). A light beige solid product (1.067 g, 52% yield) was obtained.

[0174] 11H NMR (300 MHz, chloroform-d) δ 8.37 (d, J = 2.0 Hz, 1H), 7.37 (dd, J = 1.9, 0.6 Hz, 1H), 6.88 (d, J = 1.6 Hz, 1H), 5.68 (d, J = 0.6 Hz, 1H).

[0175] 13 13C NMR (75 MHz, CDCl3) δ 151.18, 146.44, 145.05, 133.78, 120.23, 88.86, 50.61.

[0176] Preparation Example 5: 3-Bromo-6-chlorofuro[3,2-b]pyridine

[0177]

[0178] 2,3-Dibromo-6-chloro-2,3-dihydrofuro[3,2-b]pyridine (Preparation Example 4; 1.0 g, 3.2 mmol) was dissolved in toluene (15 mL), DBU (1.6 mL, 11.0 mmol) was added, and the resulting mixture was stirred at 80 °C for 45 minutes. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 5:1). A white solid product (514 mg, 69% yield) was obtained.

[0179] 1 1H NMR (500 MHz, chloroform-d) δ 8.61 (d, J = 2.0 Hz, 1H), 7.89 (s, 1H), 7.82 (d, J = 2.0 Hz, 1H).

[0180] 13 13C NMR (126 MHz, chloroform-d) δ 147.40, 147.27, 146.29, 143.52, 128.86, 119.34, 99.71.

[0181] FTIR (neat), cm -1 : 3094, 3041, 1536, 1457, 1379, 1285, 1074, 995, 910, 875, 772, 603, 496.

[0182] HRMS (APCI): Calcd for C7H3BrClNO [M+H] + = 231.9159, found = 231.9162.

[0183] Preparation Example 6: 6-Chloro-3-(2,6-dimethylpyridin-4-yl)furo[3,2-b]pyridine

[0184]

[0185] Using 332 mg (1.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 400 mg (1.716 mmol) of 2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, the compound was prepared by General Procedure A; the reaction time was 1 hour; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 0:1) gave the compound as a yellow solid (300 mg, 81% yield).

[0186] 1 1H NMR (500 MHz, chloroform-d) δ 8.62 (d, J = 2.0 Hz, 1H), 8.20 (s, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.62 (s, 2H), 2.60 (s, 6H).

[0187] 13 13C NMR (126 MHz, CDCl3) δ 158.56, 148.60, 147.05, 145.65, 143.95, 138.13, 128.12, 120.08, 119.05, 117.94, 77.16, 24.81.

[0188] HRMS (APCI): Calcd for C 14 H 11 ClN2O [M+H] + = 259.0633, found = 259.0636.

[0189] FTIR (neat), cm -1 : 3142, 3019, 2959, 2920, 2850, 1617, 1550, 1383, 1372, 1350, 1277, 1131, 1107, 1081, 910, 896, 880, 846, 806, 782, 597, 561, 546, 525, 456.

[0190] Preparation Example 7: tert-Butyl 4-(4-(3-(2,6-dimethylpyridin-4-yl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0191]

[0192] Using 112 mg (0.433 mmol) of 6-chloro-3-(2,6-dimethylpyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 6) and 202 mg (0.520 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 1 hour; flash chromatography (cyclohexane / EtOAc, gradient from 4:1 to 2:3) gave the compound as a white solid (122 mg, 58% yield).

[0193] 1 1H NMR (500 MHz, chloroform-d) δ 8.90 (d, J = 1.9 Hz, 1H), 8.22 (s, 1H), 7.93 (d, J = 1.9 Hz, 1H), 7.70 (s, 2H), 7.57 (d, J = 8.7 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 3.66 - 3.54 (m, 4H), 3.23 (t, J = 5.2 Hz, 4H), 2.62 (s, 6H), 1.50 (s, 9H).

[0194] 13 13C NMR (126 MHz, CDCl3) δ 158.48, 154.87, 151.22, 149.57, 146.43, 145.41, 143.93, 138.86, 133.46, 129.23, 128.36, 120.03, 118.02, 116.85, 116.24, 80.17, 49.04, 43.55, 28.59, 24.85.

[0195] HRMS (APCI): Calcd for C 29 H 32 N4O3 [M + H] + = 485.2547, found = 485.2549.

[0196] FTIR (neat), cm -1 : 2978, 1678, 1608, 1524, 1430, 1388, 1365, 1239, 1180, 826, 812, 546, 459, 413.

[0197] Preparation Example 8: 3-(2,6-Dimethylpyridin-4-yl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2- b]pyridine

[0198]

[0199] TFA (0.5 mL, 6.535 mmol) was added to a solution of tert-butyl 4-(4-(3-(2,6-dimethylpyridin-4-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 7; 100 mg, 0.206 mmol) in DCM (5 mL). The reaction mixture was stirred at 23 °C for 2 h. All volatiles were evaporated in vacuo, and the residue was dissolved in acetonitrile (5 mL). Triethylamine (0.15 mL) was added, and the mixture was stirred for 2 min. The yellow solid product was collected by filtration (56 mg, 71% yield).

[0200] 1 H NMR (500 MHz, methanol-d4) δ 8.87 (d, J = 1.9 Hz, 1H), 8.64 (s, 1H), 8.12 (d, J = 1.9 Hz, 1H), 7.88 (s, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 8.9 Hz, 2H), 3.33 - 3.27 (m, 4H), 3.12 - 3.07 (m, 4H), 2.61 (s, 6H).

[0201] 13 C NMR (126 MHz, MeOD) δ 159.05, 152.95, 151.05, 149.48, 145.84, 144.41, 141.31, 134.96, 129.72, 129.03, 120.13, 119.44, 117.61, 117.27, 50.21, 46.32, 23.84.

[0202] HRMS (APCI): Calcd for C 24 H 24 N4O [M + H] + = 385.2023; Found [M + H] + = 385.2025.

[0203] FTIR (neat), cm -1 : 1667, 1604, 1523, 1480, 1375, 1229, 1199, 1182, 1120, 1099, 827, 808, 539.

[0204] Preparation Example 9: 6-Chloro-3-(pyridin-3-yl)furo[3,2-b]pyridine

[0205]

[0206] Compound was prepared by General Procedure A using 200 mg (0.86 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 137 mg (1.120 mmol) of pyridin-3-ylboronic acid; the reaction time was 1 hour; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) gave the compound as a yellow solid (104 mg, 52% yield).

[0207] 1 H NMR (500 MHz, chloroform-d) δ 9.18 (d, J = 2.4 Hz, 1H), 8.67 - 8.60 (m, 2H), 8.49 (dt, J = 7.9, 2.0 Hz, 1H), 8.19 (s, 1H), 7.86 (d, J = 2.0 Hz, 1H), 7.47 - 7.39 (m, 1H).

[0208] 13 C NMR (126 MHz, CDCl3) δ 148.96, 148.52, 147.82, 145.73, 145.69, 144.10, 134.84, 128.24, 126.45, 123.94, 119.10, 119.02.

[0209] HRMS (APCI): Calcd for C 12 H7ClN2O [M + H] + = 231.0320; Found [M + H] + = 231.0322.

[0210] FTIR (neat), cm -1 : 3070, 3039, 1610, 1468, 1425, 1388, 1365, 1326, 1281, 1142, 1093, 1077, 1030, 968, 911, 891, 801, 787, 733, 704, 619, 597, 528.

[0211] Preparation Example 10: tert-Butyl 4-(4-(3-(pyridin-3-yl)furo[3,2-b]pyridin-6-yl)phenyl)pi perazine-1-carboxylate

[0212]

[0213] Using 96 mg (0.416 mmol) of 6-chloro-3-(pyridin-3-yl)furo[3,2-b]pyridine (Preparation Example 9) and 194 mg (0.499 mmol) of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:2) gave the compound as a yellow solid (171 mg, 90% yield).

[0214] 1 H NMR (500 MHz, chloroform-d) δ 9.21 (dd, J = 2.3, 0.9 Hz, 1H), 8.88 (d, J = 1.9 Hz, 1H), 8.61 (dd, J = 4.9, 1.7 Hz, 1H), 8.57 (ddd, J = 7.9, 2.2, 1.7 Hz, 1H), 8.19 (s, 1H), 7.95 (d, J = 1.9 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.44 (ddd, J = 7.8, 4.8, 0.9 Hz, 1H), 7.05 (d, J = 8.9 Hz, 2H), 3.62 (dd, J = 6.3, 4.1 Hz, 4H), 3.23 (dd, J = 6.3, 4.1 Hz, 4H), 1.50 (s, 9H).

[0215] 13 C NMR (126 MHz, CDCl3) δ 154.88, 151.22, 149.42, 148.61, 147.78, 145.42, 145.04, 144.04, 134.90, 133.56, 129.25, 128.39, 127.13, 123.95, 118.89, 116.86, 116.26, 80.17, 49.05, 43.66, 28.60.

[0216] HRMS (APCI): Calcd for C 27 H 28 N4O3 [M + H] + = 457.2234; Found [M + H] + = 457.2237.

[0217] FTIR (neat), cm -1 2977, 2929, 2900, 2857, 2823, 1681, 1608, 1526, 1483, 1462, 1421, 1380, 1362, 1342, 1283, 1239, 1204, 1161, 1128, 1097, 1048, 966, 909, 821, 795, 765, 706, 546, 524.

[0218] Preparation Example 11: 6-(4-(Piperazin-1-yl)phenyl)-3-(pyridin-3-yl)furo[3,2-b]pyridine

[0219]

[0220] Using 90 mg (0.197 mmol) of tert-butyl 4-(4-(3-(pyridin-3-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 10), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a pale yellow solid (71 mg, 100% yield).

[0221] 1 H NMR (300 MHz, DMSO-d6) δ 9.43 (d, J = 2.2 Hz, 1H), 8.96 (s, 2H), 8.62 (dd, J = 8.0, 2.1 Hz, 1H), 8.58 (dd, J = 4.8, 1.7 Hz, 1H), 8.35 (d, J = 1.9 Hz, 1H), 7.71 (d, J = 8.5 Hz, 2H), 7.54 (dd, J = 7.9, 4.8 Hz, 1H), 7.06 (d, J = 8.5 Hz, 2H), 3.16 (dd, J = 6.4, 3.7 Hz, 4H), 2.89 (t, J = 5.0 Hz, 4H).

[0222] 13 C NMR (126 MHz, DMSO) δ 151.25, 148.79, 148.45, 147.41, 147.08, 144.45, 142.98, 133.56, 132.57, 127.72, 126.68, 126.57, 123.73, 117.33, 115.68, 115.45, 48.57, 45.23.

[0223] HRMS (APCI): Calcd for C 22 H 20 N4O [M + H] + = 357.1710; Found [M + H] + = 357.1710.

[0224] FTIR (neat), cm -1: 3289, 3033, 2945, 2825, 2748, 1604, 1522, 1481, 1449, 1377, 1333, 1234, 1201, 1144, 1125, 1099, 966, 946, 884, 822, 803, 787, 704, 683, 608, 537。

[0225] Preparation Example 12: 6-Chloro-3-(3-methoxyphenyl)furo[3,2-b]pyridine

[0226]

[0227] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 85 mg (0.559 mmol) of (3-methoxyphenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 11:1) gave the compound as a white solid (68 mg, 61% yield).

[0228] 1 1H NMR (500 MHz, chloroform-d) δ 8.62 (d, J = 2.0 Hz, 1H), 8.10 (s, 1H), 7.81 (d, J = 2.0 Hz, 1H), 7.65 (dd, J = 2.6, 1.6 Hz, 1H), 7.58 (ddd, J = 7.6, 1.6, 0.9 Hz, 1H), 7.39 (t, J = 8.0 Hz, 1H), 6.93 (ddd, J = 8.3, 2.6, 0.9 Hz, 1H), 3.89 (s, 3H).

[0229] 13 13C NMR (126 MHz, CDCl3) δ 160.14, 148.52, 145.77, 145.33, 144.48, 131.24, 130.03, 127.71, 121.87, 119.61, 118.80, 113.69, 113.07, 55.47.

[0230] HRMS (APCI): Calcd for C 14 H 10 ClNO2 [M + H] + = 260.0473; Found [M + H] + = 260.0476.

[0231] FTIR (neat), cm -1: 3108, 3068, 2964, 2942, 2838, 1611, 1584, 1564, 1480, 1451, 1438, 1387, 1343, 1304, 1287, 1274, 1234, 1209, 1183, 1170, 1128, 1096, 1084, 1071, 1051, 999, 987, 911, 887, 875, 859, 822, 780, 685, 654, 599, 569, 525, 457。

[0232] Preparation Example 13: tert-Butyl 4-(4-(3-(3-methoxyphenyl)furo[3,2-b]pyridin-6-yl)phenyl) piperazine-1-carboxylate

[0233]

[0234] Using 65 mg (0.250 mmol) of 6-chloro-3-(3-methoxyphenyl)furo[3,2-b]pyridine (Preparation Example 12) and 126 mg (0.325 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:1) gave a yellow solid compound (88 mg, 72% yield).

[0235] 1 H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.9 Hz, 1H), 8.11 (s, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.70 (dd, J = 2.6, 1.5 Hz, 1H), 7.66 (dt, J = 7.8, 1.2 Hz, 1H), 7.63 - 7.55 (m, 2H), 7.40 (t, J = 7.9 Hz, 1H), 7.05 (d, J = 8.6 Hz, 2H), 6.92 (ddd, J = 8.3, 2.6, 1.0 Hz, 1H), 3.90 (s, 3H), 3.67 - 3.57 (m, 4H), 3.23 (t, J = 5.1 Hz, 4H), 1.50 (s, 9H).

[0236] 13 C NMR (126 MHz, CDCl3) δ 160.15, 154.88, 149.44, 145.17, 145.11, 144.48, 133.02, 131.91, 130.02, 128.38, 121.85, 119.74, 116.96, 116.11, 113.53, 113.01, 80.18, 55.50, 49.21, 43.56, 28.60.

[0237] HRMS(APCI): Calculated value C 29 H 31 N3O4[M+H] + = 486.2387; Measured value [M+H] + = 486.2391.

[0238] FTIR (neat), cm -1 2974, 2815, 1682, 1604, 1590, 1524, 1480, 1461, 1449, 1412, 1378, 1366, 1336, 1290, 1261, 1251, 1224, 1160, 1134, 1117, 1101, 1042, 996, 908, 887, 860, 826, 813, 791, 773, 693, 544.

[0239] Preparation Example 14: 3-(3-Methoxyphenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[0240]

[0241] Using 80 mg (0.165 mmol) of tert-butyl 4-(4-(3-(3-methoxyphenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 13), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 6:1) gave the compound as a white solid (43 mg, 68% yield).

[0242] 1 H NMR (500 MHz, DMSO-d6) δ 8.93 (d, J = 2.0 Hz, 1H), 8.85 (s, 1H), 8.29 (d, J = 1.9 Hz, 1H), 7.88 (dd, J = 2.6, 1.5 Hz, 1H), 7.85 (dt, J = 7.7, 1.2 Hz, 1H), 7.70 (d, J = 8.9 Hz, 2H), 7.41 (t, J = 7.9 Hz, 1H), 7.15 - 7.03 (m, 2H), 6.95 (ddd, J = 8.3, 2.6, 1.0 Hz, 1H), 3.84 (s, 3H), 3.21 - 3.13 (m, 4H), 2.93 - 2.86 (m, 4H).

[0243] 1313C NMR (126 MHz, DMSO) δ 159.48, 151.17, 148.85, 146.85, 144.23, 143.30, 132.24, 131.67, 129.68, 127.70, 126.86, 119.88, 118.88, 115.52, 115.49, 112.94, 112.26, 55.12, 48.51, 45.18。

[0244] HRMS (APCI): Calculated for C 24 H 23 N3O2 [M+H] + = 386.1863; Found [M+H] + = 386.1864。

[0245] FTIR (neat), cm -1 : 2829, 1603, 1590, 1523, 1481, 1450, 1377, 1261, 1242, 1227, 1117, 1100, 1038, 910, 887, 859, 827, 814, 793, 693, 543, 517。

[0246] Preparation Example 15: 6-Chloro-3-(2-methoxyphenyl)furo[3,2-b]pyridine

[0247]

[0248] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 85 mg (0.559 mmol) of (2-methoxyphenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 11:1) gave the compound as a white solid (110 mg, 98% yield).

[0249] 1 1H NMR (500 MHz, chloroform-d) δ 8.82 (dd, J = 7.7, 1.8 Hz, 1H), 8.61 (d, J = 2.1 Hz, 1H), 8.51 (s, 1H), 7.80 (d, J = 2.1 Hz, 1H), 7.34 (ddd, J = 8.3, 7.4, 1.8 Hz, 1H), 7.15 (td, J = 7.5, 1.2 Hz, 1H), 7.02 (dd, J = 8.2, 1.1 Hz, 1H), 3.95 (s, 3H).

[0250] 1313C NMR (126 MHz, CDCl3) δ 156.79, 149.33, 147.53, 145.28, 144.64, 129.92, 128.61, 127.20, 121.10, 119.22, 118.47, 116.55, 110.85, 55.55.

[0251] HRMS (APCI): Calcd for C 14 H 10 ClNO2 [M + H] + = 260.0473; Found [M + H] + = 260.0475.

[0252] FTIR (neat), cm -1 : 3178, 3068, 2921, 2836, 1601, 1579, 1495, 1453, 1434, 1385, 1339, 1251, 1185, 1135, 1121, 1092, 1072, 1053, 1021, 962, 940, 920, 908, 867, 809, 774, 744, 733, 698, 645, 593, 582, 534, 474, 464.

[0253] Preparation Example 16: tert-Butyl 4-(4-(3-(2-methoxyphenyl)furo[3,2-b]pyridin-6-yl)phenyl) piperazine-1-carboxylate

[0254]

[0255] Using 100 mg (0.385 mmol) of 6-chloro-3-(2-methoxyphenyl)furo[3,2-b]pyridine (Preparation Example 15) and 194 mg (0.501 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 4:1) gave the compound as a white solid (180 mg, 96% yield).

[0256] 11H NMR (500 MHz, chloroform-d) δ 8.91 (dd, J = 7.7, 1.8 Hz, 1H), 8.88 (d, J = 1.9 Hz, 1H), 8.53 (s, 1H), 7.92 (d, J = 1.9 Hz, 1H), 7.62 - 7.54 (m, 2H), 7.33 (ddd, J = 8.2, 7.4, 1.8 Hz, 1H), 7.17 (td, J = 7.5, 1.2 Hz, 1H), 7.09 - 7.02 (m, 3H), 3.98 (s, 3H), 3.67 - 3.45 (m, 4H), 3.23 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H).

[0257] 13 13C NMR (126 MHz, CDCl3) δ 156.84, 154.88, 151.01, 148.77, 148.43, 145.26, 144.46, 132.54, 130.03, 129.76, 128.35, 128.31, 121.18, 119.87, 116.91, 116.52, 115.88, 110.90, 80.13, 55.61, 49.16, 43.71, 28.60.

[0258] HRMS (APCI): Calcd for C 29 H 31 N3O4 [M + H] + = 486.2387; Found [M + H] + = 486.2390.

[0259] FTIR (neat), cm -1 2970, 2834, 1678, 1519, 1495, 1463, 1426, 1381, 1363, 1288, 1266, 1249, 1213, 1198, 1161, 1142, 1118, 1094, 1085, 1056, 1042, 1030, 1003, 964, 915, 863, 832, 779, 767, 746, 671, 650, 554, 539, 481.

[0260] Preparation Example 17: 3-(2-Methoxyphenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[0261]

[0262] Using 100 mg (0.206 mmol) of 1) tert-butyl 4-(4-(3-(2-methoxyphenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 16), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 4:1) gave the compound as a white solid (67 mg, 84% yield).

[0263] 1 H NMR (500 MHz, DMSO-d6) δ 9.00 (dd, J = 7.7, 1.8 Hz, 1H), 8.93 (d, J = 2.0 Hz, 1H), 8.78 (s, 1H), 8.29 (d, J = 2.0 Hz, 1H), 7.77 - 7.66 (m, 2H), 7.41 - 7.34 (m, 1H), 7.18 (dd, J = 8.4, 1.1 Hz, 1H), 7.13 (td, J = 7.5, 1.1 Hz, 1H), 7.07 - 7.03 (m, 2H), 3.96 (s, 3H), 3.14 (dd, J = 6.2, 4.0 Hz, 4H), 2.91 - 2.82 (m, 4H).

[0264] 13 C NMR (126 MHz, DMSO) δ 156.42, 151.30, 148.73, 147.75, 143.99, 143.77, 132.06, 129.01, 128.36, 127.67, 126.81, 120.34, 119.06, 115.45, 115.39, 115.32, 111.15, 55.46, 48.81, 45.41.

[0265] HRMS (APCI): Calcd for C 24 H 23 N3O2 [M + H] + = 386.1863; Found [M + H] + = 386.1866.

[0266] FTIR (neat), cm -1 : 2932, 2915, 2814, 1603, 1518, 1498, 1466, 1454, 1434, 1419, 1372, 1302, 1247, 1224, 1200, 1189, 1146, 1115, 1090, 1076, 1057, 1021, 963, 919, 882, 829, 809, 780, 764, 722, 697, 650, 545.

[0267] Preparation Example 18:3-(6-Chlorofuro[3,2-b]pyridin-3-yl)benzonitrile

[0268]

[0269] Using 300 mg (1.29 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 247 mg (1.680 mmol) of (3-cyanophenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 0:1) gave the compound as a white solid (320 mg, 97% yield).

[0270] 1 1H NMR (500 MHz, chloroform-d) δ 8.63 (d, J = 2.0 Hz, 1H), 8.43 (t, J = 1.7 Hz, 1H), 8.28 (dt, J = 7.8, 1.5 Hz, 1H), 8.18 (s, 1H), 7.86 (d, J = 2.0 Hz, 1H), 7.65 (dt, J = 7.7, 1.4 Hz, 1H), 7.58 (t, J = 7.8 Hz, 1H).

[0271] 13 13C NMR (126 MHz, CDCl3) δ 148.59, 146.13, 145.72, 143.74, 131.52, 131.46, 131.18, 130.66, 129.81, 128.33, 120.07, 119.16, 118.79, 113.36.

[0272] HRMS (APCI): Calcd for C 14 H7ClN2O [M+H] + = 255.0320; Found [M+H] + = 255.0322.

[0273] FTIR (neat), cm -1 : 3104, 3069, 2230, 1610, 1586, 1479, 1466, 1384, 1344, 1275, 1131, 1101, 1091, 1072, 1012, 911, 893, 881, 837, 814, 788, 679, 659, 601, 515, 474, 463.

[0274] Preparation Example 19: tert-Butyl 4-(4-(3-(3-cyanophenyl)furo[3,2-b]pyridin-6-yl)phenyl)pi perazine-1-carboxylate

[0275]

[0276] Using 300 mg (1.178 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzonitrile (Preparation Example 18) and 595 mg (1.532 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 3:1) gave the compound as a white solid (368 mg, 65% yield).

[0277] 1 H NMR (500 MHz, chloroform-d) δ 8.89 (d, J = 1.9 Hz, 1H), 8.49 (t, J = 1.7 Hz, 1H), 8.35 (dt, J = 7.8, 1.5 Hz, 1H), 8.17 (s, 1H), 7.94 (d, J = 1.9 Hz, 1H), 7.64 (dt, J = 7.8, 1.5 Hz, 1H), 7.62 - 7.55 (m, 3H), 7.09 - 7.02 (m, 2H), 3.62 (t, J = 5.2 Hz, 4H), 3.24 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H).

[0278] 13 C NMR (126 MHz, CDCl3) δ 154.87, 151.20, 149.52, 145.44, 145.43, 143.69, 133.63, 132.21, 131.22, 131.18, 130.66, 129.76, 129.21, 128.39, 120.01, 118.94, 116.88, 116.29, 113.28, 80.18, 49.07, 43.58, 28.59.

[0279] HRMS (APCI): Calcd for C 29 H 28 N4O3 [M + H] + = 481.2234; Found [M + H] + = 481.2231.

[0280] FTIR (neat), cm -1 3467, 2976, 2930, 2820, 2229, 1684, 1604, 1527, 1480, 1411, 1380, 1364, 1237, 1212, 1161, 1119, 1044, 1011, 995, 907, 817, 797, 773, 686, 538, 524, 478.

[0281] Preparation Example 20: 3-(6-(4-(Piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzonitrile

[0282]

[0283] TFA (0.5 mL, 6.535 mmol) was added to a solution of tert-butyl 4-(4-(3-(3-cyanophenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 19; 75 mg, 0.156 mmol) in DCM (5 mL). The reaction mixture was stirred at 23 °C for 2 h. All volatiles were evaporated in vacuo. The residue was dissolved in acetonitrile (5 mL), triethylamine (2.0 mL) was added, all volatiles were evaporated in vacuo, the residue was dissolved in a mixture of DCM / EA / MeOH (4:2:1; 10 mL), and extracted with NaHCO3 solution (saturated aqueous solution; 3 × 20 mL). The organic layer was dried over MgSO4 and filtered. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (DCM / MeOH; gradient from 1:0 to 4:1). A white solid product (43 mg, 72% yield) was obtained.

[0284] 1 H NMR (500 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.97 (d, J = 2.0 Hz, 1H), 8.75 (t, J = 1.7 Hz, 1H), 8.62 (dt, J = 8.0, 1.4 Hz, 1H), 8.33 (d, J = 1.9 Hz, 1H), 7.83 (dt, J = 7.6, 1.4 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.71 - 7.67 (m, 2H), 7.11 - 6.99 (m, 2H), 3.15 (dd, J = 6.1, 4.0 Hz, 4H), 2.95 - 2.82 (m, 4H).

[0285] 13 C NMR (126 MHz, DMSO) δ 151.34, 148.91, 147.74, 144.49, 142.69, 132.63, 131.89, 130.90, 130.85, 129.98, 129.57, 127.71, 126.55, 118.72, 118.12, 115.73, 115.41, 111.82, 48.72, 45.36.

[0286] HRMS (APCI): Calcd for C 24 H 20 N4O [M + H] + = 381.1710; Found [M + H] + = 381.1714.

[0287] FTIR (neat), cm -1 : 3587, 3319, 2230, 1663, 1601, 1524, 1481, 1453, 1378, 1351, 1241, 1210, 1146, 1104, 1054, 1011, 887, 852, 797, 749, 726, 686, 666, 637, 621, 526, 477。

[0288] Preparation Example 21: 6-Chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine

[0289]

[0290] Using 200 mg (0.86 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 137 mg (1.120 mmol) of pyridin-4-ylboronic acid, the compound was prepared by General Procedure A; the reaction time was 1 hour; flash chromatography (cyclohexane / EtOAc, 0% to 50% EtOAc gradient) gave the compound as a yellow solid (108 mg, 54% yield).

[0291] 1 1H NMR (500 MHz, chloroform-d) δ 8.71 (d, J = 6.2 Hz, 2H), 8.65 (d, J = 2.0 Hz, 1H), 8.28 (s, 1H), 8.07 - 7.98 (m, 2H), 7.88 (d, J = 2.1 Hz, 1H).

[0292] 13 13C NMR (126 MHz, CDCl3) δ 150.18, 148.74, 147.29, 145.91, 143.75, 138.22, 128.43, 121.47, 119.64, 119.25。

[0293] HRMS (APCI): Calcd for C 12 H7ClN2O [M+H] + = 231.0320; Found [M+H] + = 231.0319。

[0294] FTIR (neat), cm -1 : 3062, 1610, 1422, 1388, 1284, 1231, 1144, 1090, 995, 979, 914, 880, 824, 729, 655, 618, 600, 518, 427。

[0295] Preparation Example 22: 6-Phenyl-3-(pyridin-4-yl)furo[3,2-b]pyridine

[0296]

[0297] Using 50 mg (0.217 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 34 mg (0.282 mmol) of phenylboronic acid, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 4:1) gave the compound as a white solid (56 mg, 95% yield).

[0298] 1 H NMR (500 MHz, chloroform-d) δ 8.93 (d, J = 1.9 Hz, 1H), 8.73 (bs, 2H), 8.30 (s, 1H), 8.07 (d, J = 5.7 Hz, 2H), 8.00 (d, J = 1.8 Hz, 1H), 7.69 - 7.62 (m, 2H), 7.52 (t, J = 7.6 Hz, 2H), 7.48 - 7.40 (m, 1H).

[0299] 13 C NMR (126 MHz, CDCl3) δ 150.43, 149.48, 146.87, 145.93, 144.42, 138.43, 137.96, 133.97, 129.38, 128.33, 127.68, 121.47, 119.64, 117.16.

[0300] HRMS (APCI): Calcd for C 18 H 12 N2O [M + H] + = 273.1022; Found [M + H] + = 273.1020.

[0301] FTIR (neat), cm -1 3043, 1602, 1384, 1367, 1204, 1098, 979, 882, 829, 787, 756, 699, 680, 633, 536, 525, 508.

[0302] Preparation Example 23: 6-(6-Morpholinopyridin-3-yl)-3-(pyridin-4-yl)furo[3,2-b]pyridine

[0303]

[0304] Using 50 mg (0.217 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 88 mg (0.282 mmol) of 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 0:1) gave the compound as a pale orange solid (35 mg, 45% yield).

[0305] 1 H NMR (500 MHz, DMSO-d6) δ 9.09 (s, 1H), 8.99 (s, 1H), 8.69 (d, J = 5.3 Hz, 2H), 8.63 (d, J = 2.6 Hz, 1H), 8.42 (s, 1H), 8.25 (d, J = 5.0 Hz, 2H), 8.05 (dd, J = 8.8, 2.7 Hz, 1H), 6.98 (d, J = 8.9 Hz, 1H), 3.73 (t, J = 4.8 Hz, 4H), 3.54 (t, J = 4.8 Hz, 4H).

[0306] 13 C NMR (126 MHz, DMSO) δ 158.48, 149.78, 148.74, 148.70, 145.89, 144.18, 142.94, 137.71, 135.96, 130.13, 121.86, 120.56, 117.76, 115.60, 106.78, 65.70, 44.92.

[0307] HRMS (APCI): Calcd for C 21 H 18 N4O2 [M + H] + = 359.1503; Found [M + H] + = 359.1504.

[0308] FTIR (neat), cm -1 3040, 2978, 2879, 2856, 1604, 1509, 1478, 1409, 1384, 1320, 1236, 1206, 1119, 1088, 1055, 942, 822, 802, 722, 671, 638, 524, 475.

[0309] Preparation Example 24: tert-Butyl 4-(5-(3-(pyridin-4-yl)furo[3,2-b]pyridin-6-yl)pyridin-2- yl)piperazine-1-carboxylate

[0310]

[0311] Using 50 mg (0.217 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 110 mg (0.282 mmol) of 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)-1-Boc-piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 0:1) gave the compound as a light brown solid (92 mg, 93% yield).

[0312] 1 1H NMR (500 MHz, chloroform-d) δ 8.86 (d, J = 1.9 Hz, 1H), 8.73 (bs, 2H), 8.50 (dd, J = 2.6, 0.7 Hz, 1H), 8.29 (s, 1H), 8.06 (d, J = 3.6 Hz, 2H), 7.93 (d, J = 1.9 Hz, 1H), 7.78 (dd, J = 8.7, 2.6 Hz, 1H), 6.77 (dd, J = 8.9, 0.7 Hz, 1H), 3.63 (dd, J = 6.7, 3.3 Hz, 4H), 3.58 (dd, J = 6.6, 3.3 Hz, 4H), 1.50 (s, 9H).

[0313] 13 13C NMR (126 MHz, CDCl3) δ 158.92, 154.97, 150.35, 149.58, 146.74, 146.70, 145.10, 144.01, 138.52, 136.57, 131.22, 123.13, 121.51, 119.63, 116.06, 107.27, 80.23, 45.14, 43.44, 28.60.

[0314] HRMS (APCI): Calcd for C 26 H 27 N5O3 [M + H] + = 458.2187; Found [M + H] + = 458.2190.

[0315] FTIR (neat), cm -12999,2973,2844,1680,1602,1509,1473,1456,1402,1365,1282,1267,1240,1208,1165,1125,1106,1088,1055,1003,978,936,892,807,792,776,757,676,663,653,637,552,529,516。

[0316] Preparation Example 25: 6-(6-(Piperazin-1-yl)pyridin-3-yl)-3-(pyridin-4-yl)furo[3,2-b]py Pyridine

[0317]

[0318] Using 85 mg (0.186 mmol) of tert-butyl 4-(5-(3-(pyridin-4-yl)furo[3,2-b]pyridin-6-yl)pyridin-2-yl)piperazine-1-carboxylate (Preparation Example 24), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a pale yellow solid (65 mg, 98% yield).

[0319] 1 H NMR (500 MHz, DMSO-d6) δ 9.10 (s, 1H), 8.97 (s, 1H), 8.68 (d, J = 5.1 Hz, 2H), 8.60 (s, 1H), 8.40 (s, 1H), 8.25 (d, J = 5.1 Hz, 2H), 8.00 (d, J = 9.1 Hz, 1H), 6.93 (d, J = 9.0 Hz, 1H), 3.49 (t, J = 4.9 Hz, 4H), 2.79 (t, J = 5.0 Hz, 4H).

[0320] 13 C NMR (126 MHz, DMSO) δ 158.76, 150.07, 149.03, 148.94, 146.10, 144.28, 142.93, 137.90, 136.03, 130.41, 121.17, 120.68, 117.80, 115.68, 106.81, 45.79, 45.40.

[0321] HRMS (APCI): Calcd for C 21 H 19 N5O [M+H] + = 358.1662; Found [M+H] + = 358.1663.

[0322] FTIR (neat), cm-1 : 3267, 2840, 1600, 1510, 1475, 1449, 1409, 1377, 1322, 1247, 1206, 1100, 900, 829, 810, 670, 656, 637, 543, 528, 483。

[0323] Preparation Example 26: tert-Butyl 4-(5-(6-chlorofuro[3,2-b]pyridin-3-yl)pyridin-2-yl)piperazine-1- carboxylate

[0324]

[0325] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 218 mg (0.559 mmol) of 4-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)-1-Boc-piperazine, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) gave the compound as a white solid (105 mg, 59% yield).

[0326] 1 1H NMR (500 MHz, chloroform-d) δ 8.77 (dd, J = 2.4, 0.8 Hz, 1H), 8.58 (d, J = 2.0 Hz, 1H), 8.21 (dd, J = 8.8, 2.4 Hz, 1H), 8.04 (s, 1H), 7.81 (d, J = 2.1 Hz, 1H), 6.75 (dd, J = 8.9, 0.8 Hz, 1H), 3.64 - 3.51 (m, 8H), 1.49 (s, 9H).

[0327] 13 13C NMR (126 MHz, CDCl3) δ 158.79, 154.98, 148.37, 146.48, 145.25, 144.63, 144.13, 136.53, 127.77, 119.48, 118.79, 115.84, 107.11, 80.13, 45.24, 43.48, 28.60, 27.08.

[0328] HRMS (APCI): Calcd for C 21 H 23 ClN4O3 [M + H] + = 415.1531; Found [M + H] + = 415.1530.

[0329] FTIR (neat), cm -1: 3085, 2982, 2929, 2891, 2865, 2832, 1691, 1603, 1582, 1487, 1461, 1426, 1384, 1365, 1318, 1279, 1239, 1224, 1185, 1169, 1134, 1082, 1072, 1053, 1026, 1002, 962, 932, 907, 872, 811, 783, 764, 752, 595, 528, 464。

[0330] Preparation Example 27: tert-Butyl 4-(5-(6-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)furo[3, 2-b]pyridin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

[0331]

[0332] Using 95 mg (0.229 mmol) of tert-butyl 4-(5-(6-chlorofuro[3,2-b]pyridin-3-yl)pyridin-2-yl)piperazine-1-carboxylate (Preparation Example 26) and 116 mg (0.298 mmol) of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:1) gave the compound as a yellow solid (99 mg, 67% yield).

[0333] 1 H NMR (500 MHz, chloroform-d) δ 8.84 (d, J = 1.9 Hz, 1H), 8.81 (dd, J = 2.4, 0.8 Hz, 1H), 8.30 (dd, J = 8.7, 2.3 Hz, 1H), 8.04 (s, 1H), 7.90 (d, J = 1.9 Hz, 1H), 7.63 - 7.52 (m, 2H), 7.11 - 7.00 (m, 2H), 6.78 (d, J = 8.8 Hz, 1H), 3.65 - 3.55 (m, 12H), 3.23 (t, J = 5.2 Hz, 4H), 1.50 (s, 18H).

[0334] 13 C NMR (126 MHz, CDCl3) δ 154.98, 154.88, 151.13, 149.25, 145.07, 144.58, 143.54, 133.13, 129.55, 128.36, 116.88, 116.65, 116.05, 80.15, 49.11, 45.40, 43.66, 28.60.

[0335] HRMS (APCI): Calculated for C 36 H 44 N6O5 [M + H]+ = 641.3446; Measured value [M+H] + = 641.3449.

[0336] FTIR (neat), cm -1 2976, 2826, 1689, 1608, 1580, 1524, 1489, 1454, 1408, 1364, 1285, 1235, 1204, 1162, 1121, 1084, 1050, 998, 963, 928, 863, 819, 800, 771, 730, 647, 606, 540, 461.

[0337] Preparation Example 28: 6-(4-(Piperazin-1-yl)phenyl)-3-(6-(piperazin-1-yl)pyridin-3-yl)furo [3,2-b]pyridine

[0338]

[0339] Using 89 mg (0.139 mmol) of tert-butyl 4-(5-(6-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)pyridin-2-yl)piperazine-1-carboxylate (Preparation Example 27), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 4:1) gave the compound as a white solid (37 mg, 60% yield).

[0340] 1 H NMR (500 MHz, DMSO-d6) δ 8.99 (d, J = 2.4 Hz, 1H), 8.90 (d, J = 2.0 Hz, 1H), 8.69 (s, 1H), 8.31 (dd, J = 8.9, 2.4 Hz, 1H), 8.26 (d, J = 1.9 Hz, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.9 Hz, 1H), 3.53 - 3.43 (m, 4H), 3.13 (dd, J = 6.3, 3.7 Hz, 4H), 2.86 (dd, J = 6.2, 3.7 Hz, 4H), 2.81 (dd, J = 6.1, 4.1 Hz, 4H).

[0341] 1313C NMR (126 MHz, DMSO) δ 158.45, 151.32, 148.62, 145.62, 144.69, 144.05, 143.42, 135.43, 132.20, 127.66, 126.77, 117.96, 115.41, 115.37, 115.28, 106.61, 48.89, 45.75, 45.47, 45.35.

[0342] HRMS (APCI): Calcd for C 26 H 28 N6O [M + H] + = 441.2397; Found [M + H] + = 441.2397.

[0343] FTIR (neat), cm -1 : 3221, 2945, 2830, 1609, 1570, 1525, 1491, 1453, 1410, 1378, 1309, 1244, 1204, 1152, 1124, 1090, 1052, 1021, 942, 886, 817, 786, 746, 659, 533.

[0344] Preparation Example 29: 6-Chloro-3-(6-morpholinopyridin-3-yl)furo[3,2-b]pyridine

[0345]

[0346] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 162 mg (0.559 mmol) of 1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine, the compound was prepared by General Procedure A; the reaction time was 2 h; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 4:1) gave the compound as a white solid (112 mg, 82% yield).

[0347] 1 1H NMR (500 MHz, CDCl3) δ 8.78 (dd, J = 2.5, 0.8 Hz, 1H), 8.59 (d, J = 2.0 Hz, 1H), 8.24 (dd, J = 8.8, 2.4 Hz, 1H), 8.05 (s, 1H), 7.81 (d, J = 2.0 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 3.92 - 3.79 (m, 4H), 3.70 - 3.49 (m, 4H).

[0348] 1313C NMR (126 MHz, CDCl3) δ 158.89, 148.38, 146.14, 145.28, 144.59, 144.20, 136.69, 127.81, 119.37, 118.81, 116.08, 107.02, 66.86, 45.82.

[0349] HRMS (APCI): Calcd for C 16 H 14 ClN3O2 [M+H] + = 316.0847; Found [M+H] + = 316.0850.

[0350] FTIR (neat), cm -1 : 3084, 3058, 2960, 2871, 2852, 1614, 1601, 1570, 1548, 1493, 1446, 1411, 1386, 1317, 1276, 1245, 1227, 1114, 1073, 1025, 963, 942, 909, 882, 810, 794, 783, 765, 655, 595, 554, 533, 467.

[0351] Preparation Example 30: tert-Butyl 4-(4-(3-(6-morpholinopyridin-3-yl)furo[3,2-b]pyridin-6-yl) phenyl)piperazine-1-carboxylate

[0352]

[0353] Using 89 mg (0.282 mmol) of 6-chloro-3-(6-morpholinopyridin-3-yl)furo[3,2-b]pyridine (Preparation Example 29) and 142 mg (0.366 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 h; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 2:1) gave the compound as a yellow solid (106 mg, 69% yield).

[0354] 11H NMR (500 MHz, chloroform-d) δ 8.85 (d, J = 1.9 Hz, 1H), 8.81 (dd, J = 2.4, 0.8 Hz, 1H), 8.32 (dd, J = 8.9, 2.4 Hz, 1H), 8.05 (s, 1H), 7.91 (d, J = 1.9 Hz, 1H), 7.57 (d, J = 8.9 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 6.81 - 6.74 (m, 1H), 3.88 - 3.84 (m, 4H), 3.64 - 3.60 (m, 4H), 3.60 - 3.56 (m, 4H), 3.24 - 3.21 (m, 4H), 1.50 (s, 9H).

[0355] 13 13C NMR (126 MHz, CDCl3) δ 154.88, 151.13, 149.26, 145.07, 144.60, 143.54, 133.12, 129.56, 128.36, 116.88, 116.84, 116.05, 80.15, 66.90, 49.11, 45.89, 28.60.

[0356] HRMS (APCI): Calcd for C 31 H 35 N5O4 [M + H] + = 542.2762; Found [M + H] + = 542.2766.

[0357] FTIR (neat), cm -1 2970, 2853, 1688, 1607, 1579, 1524, 1489, 1451, 1411, 1379, 1365, 1266, 1235, 1203, 1162, 1118, 1088, 1050, 999, 941, 816, 798, 774, 657, 534.

[0358] Preparation Example 31: 3-(6-Morpholinopyridin-3-yl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b] pyridine

[0359]

[0360] Using 90 mg (0.166 mmol) of tert-butyl 4-(4-(3-(6-morpholinopyridin-3-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 30), the compound was prepared by General Procedure C; the reaction time was 2 h; flash chromatography (DCM / MeOH, gradient 1:0 to 4:1) gave the compound as a white solid (49 mg, 67% yield).

[0361] 1 1H NMR (500 MHz, DMSO-d6) δ 9.03 (d, J = 2.4 Hz, 1H), 8.90 (d, J = 1.9 Hz, 1H), 8.73 (s, 1H), 8.36 (dd, J = 8.8, 2.4 Hz, 1H), 8.27 (d, J = 1.9 Hz, 1H), 7.68 (d, J = 8.9 Hz, 2H), 7.04 (d, J = 8.9 Hz, 2H), 6.98 (d, J = 8.8 Hz, 1H), 3.77 - 3.68 (m, 4H), 3.60 - 3.49 (m, 4H), 3.18 - 3.08 (m, 4H), 2.89 - 2.78 (m, 4H).

[0362] 13 13C NMR (126 MHz, DMSO) δ 158.30, 151.35, 148.64, 145.58, 144.93, 144.09, 143.36, 135.54, 132.25, 127.66, 126.72, 117.83, 116.08, 115.40, 106.82, 65.90, 48.95, 45.51, 45.07.

[0363] HRMS (APCI): Calcd for C 26 H 27 N5O2 [M + H] + = 442.2238; Found [M + H] + = 442.2242.

[0364] FTIR (neat), cm -1 : 2830, 1607, 1577, 1524, 1487, 1448, 1408, 1376, 1239, 1202, 1114, 1095, 940, 883, 818, 800, 661, 534.

[0365] Preparation Example 32: 6-Chloro-3-(1-methyl-1H-pyrazol-4-yl)furo[3,2-b]pyridine

[0366]

[0367] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 116 mg (0.559 mmol) of 1-methylpyrazole-4-boronic acid pinacol ester, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 2:1) gave the compound as a white solid (59 mg, 59% yield).

[0368] 1 1H NMR (500 MHz, chloroform-d) δ 8.55 (d, J = 2.1 Hz, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.86 (s, 1H), 7.76 (d, J = 2.1 Hz, 1H), 3.97 (s, 3H).

[0369] 13 13C NMR (126 MHz, CDCl3) δ 148.00, 145.07, 144.44, 143.85, 137.09, 128.77, 127.71, 118.66, 114.69, 110.40, 39.18.

[0370] HRMS (APCI): Calcd for C 11 H8ClN3O [M + H] + = 234.0429; Found [M + H] + = 234.0428.

[0371] FTIR (neat), cm -1 : 3132, 3088, 2926, 1524, 1459, 1385, 1277, 1197, 1126, 1073, 986, 925, 902, 883, 836, 782, 773, 719, 658, 619, 588, 525, 420.

[0372] Preparation Example 33: tert-Butyl 4-(4-(3-(1-methyl-1H-pyrazol-4-yl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0373]

[0374] Using 45 mg (0.193 mmol) of 6-chloro-3-(1-methyl-1H-pyrazol-4-yl)furo[3,2-b]pyridine (Preparation Example 32) and 97 mg (0.250 mmol) of 4-(4-tert-butoxycarbonylpiperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 1:2) gave the compound as a pale yellow solid (73 mg, 82% yield).

[0375] 11H NMR (500 MHz, chloroform-d) δ 8.83 (d, J = 1.8 Hz, 1H), 8.25 (s, 1H), 8.00 (s, 1H), 7.89 (dd, J = 4.9, 1.3 Hz, 2H), 7.56 (d, J = 8.7 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 3.99 (s, 3H), 3.76 - 3.53 (m, 4H), 3.22 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H).

[0376] 13 13C NMR (126 MHz, CDCl3) δ 154.86, 151.07, 148.96, 144.84, 143.31, 137.15, 137.13, 133.15, 129.60, 128.80, 128.78, 128.35, 119.29, 118.50, 116.88, 116.07, 114.56, 110.99, 80.15, 49.11, 43.69, 39.19, 28.59.

[0377] HRMS (APCI): Calcd for C 26 H 29 N5O3 [M + H] + = 460.2343; Found [M + H] + = 460.2347.

[0378] FTIR (neat), cm -1 2978, 2930, 1677, 1607, 1526, 1484, 1461, 1420, 1384, 1363, 1340, 1281, 1263, 1237, 1224, 1170, 1130, 1085, 1065, 1047, 997, 982, 928, 909, 869, 844, 823, 793, 765, 731, 714, 690, 662, 648, 631, 607, 594, 549, 526, 502, 454, 426, 412.

[0379] Preparation Example 34: 3-(1-Methyl-1H-pyrazol-4-yl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2- b]pyridine

[0380]

[0381] Using 60 mg (0.131 mmol) of tert-butyl 4-(4-(3-(1-methyl-1H-pyrazol-4-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 33), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a beige solid (26 mg, 55% yield).

[0382] 1 H NMR (500 MHz, chloroform-d) δ 8.83 (d, J = 1.9 Hz, 1H), 8.24 (s, 1H), 7.99 (s, 1H), 7.93 - 7.85 (m, 2H), 7.55 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.8 Hz, 2H), 3.99 (s, 3H), 3.26 - 3.19 (m, 4H), 3.16 - 3.04 (m, 4H).

[0383] 13 C NMR (126 MHz, CDCl3) δ 151.62, 148.96, 144.91, 144.36, 143.18, 137.14, 133.27, 129.05, 128.75, 128.25, 116.38, 115.94, 114.55, 111.06, 50.02, 46.15, 39.18.

[0384] HRMS (APCI): Calcd for C 21 H 21 N5O [M + H] + = 360.1819; Found [M + H] + = 360.1820.

[0385] FTIR (neat), cm -1 : 3307, 2937, 2817, 2686, 2467, 1605, 1524, 1482, 1451, 1423, 1381, 1344, 1239, 1202, 1190, 1174, 1146, 1120, 1079, 984, 927, 902, 885, 829, 816, 796, 786, 751, 664, 594, 540, 528.

[0386] Preparation Example 35: 6-Chloro-3-(1-methyl-1H-pyrazol-3-yl)furo[3,2-b]pyridine

[0387]

[0388] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 116 mg (0.559 mmol) of 1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 4:1) gave the compound as a white solid (87 mg, 87% yield).

[0389] 1 H NMR (500 MHz, chloroform-d) δ 8.62 (d, J = 2.1 Hz, 1H), 8.25 (s, 1H), 7.81 (d, J = 2.1 Hz, 1H), 7.45 (d, J = 2.3 Hz, 1H), 6.98 (d, J = 2.3 Hz, 1H), 3.99 (s, 3H).

[0390] 13 C NMR (126 MHz, CDCl3) δ 148.17, 145.83, 145.54, 144.29, 141.96, 131.26, 127.62, 118.75, 116.27, 105.58, 39.29.

[0391] HRMS (APCI): Calcd for C 11 H8ClN3O [M+H] + = 234.0429; Found [M+H] + = 234.0432.

[0392] FTIR (neat), cm -1 : 3102, 2918, 2850, 1513, 1456, 1370, 1278, 1204, 1148, 1072, 1025, 924, 904, 894, 877, 851, 832, 778, 765, 685, 607, 595, 525, 424.

[0393] Preparation Example 36: tert-Butyl 4-(4-(3-(1-methyl-1H-pyrazol-3-yl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0394]

[0395] Using 80 mg (0.342 mmol) of 6-chloro-3-(1-methyl-1H-pyrazol-3-yl)furo[3,2-b]pyridine (Preparation Example 35) and 173 mg (0.445 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:3) gave a pale yellow solid compound (109 mg, 69% yield).

[0396] 1 H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.9 Hz, 1H), 8.25 (s, 1H), 7.90 (d, J = 1.9 Hz, 1H), 7.61 - 7.55 (m, 2H), 7.46 (d, J = 2.3 Hz, 1H), 7.09 - 6.99 (m, 3H), 4.00 (s, 3H), 3.75 - 3.49 (m, 4H), 3.22 (t, J = 5.2 Hz, 4H), 1.49 (s, 9H).

[0397] 13 C NMR (126 MHz, CDCl3) δ 154.87, 151.04, 149.05, 145.30, 145.12, 144.23, 142.56, 132.93, 131.15, 129.70, 128.35, 116.88, 116.19, 116.04, 105.49, 80.13, 49.13, 43.62, 39.25, 28.58.

[0398] HRMS (APCI): Calcd for C 26 H 29 N5O3 [M + H] + = 460.2343; Found [M + H] + = 460.2340.

[0399] FTIR (neat), cm -1 2971, 2821, 1688, 1460, 1426, 1384, 1366, 1288, 1236, 1222, 1202, 1173, 1131, 1090, 1073, 1048, 997, 910, 900, 821, 783, 761, 544.

[0400] Preparation Example 37: 3-(1-Methyl-1H-pyrazol-3-yl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2- b]pyridine

[0401]

[0402] Using 99 mg (0.215 mmol) of tert-butyl 4-(4-(3-(1-methyl-1H-pyrazol-3-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 36), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 4:1) gave the compound as a pale yellow solid (62 mg, 80% yield).

[0403] 1 H NMR (500 MHz, DMSO-d6) δ 9.84 (d, J = 1.9 Hz, 1H), 9.52 (s, 1H), 9.20 (d, J = 1.9 Hz, 1H), 8.75 (d, J = 2.2 Hz, 1H), 8.62 (d, J = 8.8 Hz, 2H), 8.14 - 7.86 (m, 3H), 4.13 - 3.96 (m, 4H), 3.91 - 3.65 (m, 4H).

[0404] 13 C NMR (126 MHz, DMSO) δ 160.74, 157.81, 154.66, 153.80, 152.62, 150.64, 141.72, 141.01, 137.15, 136.37, 124.91, 124.81, 124.77, 114.15, 58.29, 54.88, 48.03.

[0405] HRMS (APCI): Calcd for C 21 H 21 N5O [M + H] + = 360.1819; Found [M + H] + = 360.1815.

[0406] FTIR (neat), cm -1 : 3675, 2944, 2927, 2809, 1604, 1511, 1476, 1453, 1369, 1228, 1198, 1123, 1084, 1018, 924, 901, 886, 812, 783, 642, 542, 524, 475.

[0407] Preparation Example 38: 6-Chloro-3-(3-nitrophenyl)furo[3,2-b]pyridine

[0408]

[0409] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 93 mg (0.559 mmol) of (3-nitrophenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 9:1) gave the compound as a yellow solid (102 mg, 86% yield).

[0410] 1 H NMR (500 MHz, chloroform-d) δ 8.91 (t, J = 2.0 Hz, 1H), 8.66 (d, J = 2.0 Hz, 1H), 8.48 (dt, J = 7.8, 1.4 Hz, 1H), 8.26 (s, 1H), 8.22 (ddd, J = 8.2, 2.3, 1.1 Hz, 1H), 7.88 (d, J = 2.0 Hz, 1H), 7.66 (t, J = 8.0 Hz, 1H).

[0411] 13 C NMR (126 MHz, CDCl3) δ 148.90, 148.64, 146.40, 145.84, 143.75, 133.00, 131.89, 130.02, 128.40, 122.78, 121.87, 120.08, 119.21.

[0412] HRMS (APCI): Calcd for C 13 H7ClN2O3 [M+H] + = 275.0218; Found [M+H] + = 275.0217.

[0413] FTIR (neat), cm -1 : 3113, 1603, 1568, 1519, 1475, 1439, 1385, 1349, 1272, 1144, 1097, 1005, 917, 898, 887, 864, 828, 798, 783, 745, 733, 690, 672, 648, 620, 596, 533, 414.

[0414] Preparation Example 39: tert-Butyl 4-(4-(3-(3-nitrophenyl)furo[3,2-b]pyridin-6-yl)phenyl)pip erazine-1-carboxylate

[0415]

[0416] Using 70 mg (0.255 mmol) of 6-chloro-3-(3-nitrophenyl)furo[3,2-b]pyridine (Preparation Example 38) and 129 mg (0.331 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:1) gave the compound as a pale yellow solid (35 mg, 27% yield).

[0417] 1 H NMR (500 MHz, chloroform-d) δ 8.96 (t, J = 2.0 Hz, 1H), 8.91 (d, J = 1.9 Hz, 1H), 8.55 (dt, J = 7.8, 1.3 Hz, 1H), 8.25 (s, 1H), 8.21 (ddd, J = 8.2, 2.4, 1.0 Hz, 1H), 7.96 (d, J = 1.8 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 3.63 (d, J = 5.3 Hz, 4H), 3.25 (t, J = 5.1 Hz, 4H), 1.50 (s, 9H).

[0418] 13 C NMR (126 MHz, CDCl3) δ 154.86, 149.55, 148.90, 145.73, 145.52, 143.72, 133.64, 133.05, 132.57, 129.95, 128.43, 122.48, 121.84, 120.00, 117.02, 116.36, 80.23, 49.22, 43.70, 28.60.

[0419] HRMS (APCI): Calcd for C 28 H 28 N4O5 [M + H] + = 501.2132; Found [M + H] + = 501.2136.

[0420] FTIR (neat), cm -1 2975, 2929, 1682, 1606, 1572, 1524, 1479, 1461, 1424, 1380, 1365, 1341, 1286, 1230, 1202, 1160, 1126, 1102, 1047, 997, 909, 892, 864, 825, 804, 787, 776, 736, 692, 676, 647, 629, 607, 532, 462, 415.

[0421] Preparation Example 40: 3-(3-Nitrophenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[0422]

[0423] Using 50 mg (0.087 mmol) of tert-butyl 4-(4-(3-(3-nitrophenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 39), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a pale yellow solid (23 mg, 56% yield).

[0424] 1 H NMR (500 MHz, DMSO-d6) δ 9.28 (s, 1H), 9.12 (s, 1H), 9.03 (s, 1H), 8.67 (d, J = 7.8 Hz, 1H), 8.40 (s, 1H), 8.23 (d, J = 8.2 Hz, 1H), 7.80 (dd, J = 23.3, 8.1 Hz, 3H), 7.14 (d, J = 8.3 Hz, 2H), 3.56 - 3.43 (m, 4H), 3.21 (t, J = 5.1 Hz, 4H).

[0425] 13 C NMR (126 MHz, DMSO) δ 149.82, 148.91, 148.28, 148.24, 144.68, 142.90, 132.51, 132.41, 132.27, 130.23, 127.94, 127.86, 122.16, 120.72, 118.01, 116.17, 116.04, 45.08, 42.41.

[0426] HRMS (APCI): Calcd for C 23 H 20 N4O3 [M + H] + = 401.1608; Found [M + H] + = 401.1613.

[0427] FTIR (neat), cm -1 : 2942, 2840, 2726, 2500, 2476, 1607, 1520, 1475, 1458, 1342, 1252, 1143, 1102, 917, 808, 738, 695, 676, 531.

[0428] Preparation Example 41: 6-Chloro-3-(p-tolyl)furo[3,2-b]pyridine

[0429]

[0430] Compound was prepared by General Procedure A using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 76 mg (0.559 mmol) of p-tolylboronic acid; the reaction time was 2 hours; flash chromatography (cyclohexane) gave the compound as a white solid (103 mg, 98% yield).

[0431] 1 H NMR (500 MHz, chloroform-d) δ 8.61 (d, J = 2.1 Hz, 1H), 8.06 (s, 1H), 7.91 (d, J = 8.1 Hz, 2H), 7.80 (d, J = 2.1 Hz, 1H), 7.30 - 7.27 (m, 2H), 2.41 (s, 3H).

[0432] 13 C NMR (126 MHz, CDCl3) δ 148.46, 145.24, 145.18, 144.63, 137.98, 129.70, 127.57, 127.10, 126.99, 121.93, 118.71, 21.45.

[0433] HRMS (APCI): Calcd for C 14 H 10 ClNO [M + H] + = 244.0524; Found [M + H] + = 244.0524.

[0434] FTIR (neat), cm -1 : 3020, 2914, 2857, 1579, 1504, 1464, 1384, 1341, 1286, 1267, 1225, 1136, 1091, 1073, 966, 910, 864, 823, 802, 780, 614, 591, 523, 507.

[0435] Preparation Example 42: tert-Butyl 4-(4-(3-(p-tolyl)furo[3,2-b]pyridin-6-yl)phenyl)pip erazine-1-carboxylate

[0436]

[0437] Using 84 mg (0.345 mmol) of 6-chloro-3-(p-tolyl)furo[3,2-b]pyridine (Preparation Example 41) and 174 mg (0.448 mmol) of 4-(4-Boc-piperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 9:1) gave the compound as a white solid (23 mg, 14% yield).

[0438] 1 H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.9 Hz, 1H), 8.09 (s, 1H), 7.97 (d, J = 8.2 Hz, 2H), 7.91 (d, J = 1.9 Hz, 1H), 7.58 (d, J = 8.7 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 7.04 (d, J = 8.8 Hz, 2H), 3.62 (t, J = 5.2 Hz, 4H), 3.23 (t, J = 5.2 Hz, 4H), 2.41 (s, 3H), 1.50 (s, 9H).

[0439] 13 C NMR (126 MHz, CDCl3) δ 154.89, 151.09, 149.41, 145.02, 144.66, 144.64, 137.67, 132.93, 129.70, 129.67, 128.35, 127.69, 127.16, 121.91, 116.90, 116.04, 80.15, 49.14, 43.79, 28.60, 21.48.

[0440] HRMS (APCI): Calcd for C 29 H 31 N3O3 [M + H] + = 470.2438; Found [M + H] + = 470.2443.

[0441] FTIR (neat), cm -1 2971, 2927, 2860, 2821, 1694, 1606, 1523, 1475, 1423, 1380, 1363, 1251, 1230, 1161, 1122, 1103, 1048, 968, 912, 825, 804, 541, 530, 506.

[0442] Preparation Example 43: 6-(4-(Piperazin-1-yl)phenyl)-3-(p-tolyl)furo[3,2-b]pyridine

[0443]

[0444] Using 86 mg (0.183 mmol) of tert-butyl 4-(4-(3-(p-tolyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 42), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0% to 8:1) gave the compound as a white solid (55 mg, 81% yield).

[0445] 1 H NMR (500 MHz, DMSO-d6) δ 8.92 (d, J = 1.9 Hz, 1H), 8.77 (s, 1H), 8.27 (d, J = 2.0 Hz, 1H), 8.16 (d, J = 8.1 Hz, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.9 Hz, 2H), 3.21 - 3.09 (m, 4H), 2.91 - 2.79 (m, 4H), 2.36 (s, 3H).

[0446] 13 C NMR (126 MHz, DMSO) δ 151.23, 148.79, 146.07, 144.11, 143.41, 136.79, 132.16, 129.18, 127.67, 127.51, 126.85, 126.39, 119.99, 115.46, 115.44, 48.68, 45.30, 39.52, 20.85.

[0447] HRMS (APCI): Calcd for C 24 H 23 N3O [M + H] + = 370.1914; Found [M + H] + = 370.1914.

[0448] FTIR (neat), cm -1 : 3254, 3029, 2945, 2918, 2833, 1608, 1523, 1478, 1448, 1380, 1337, 1240, 1215, 1196, 1125, 1091, 966, 897, 815, 799, 652, 524, 508.

[0449] Preparation Example 44: 3-(3-(tert-Butylthio)phenyl)-6-chlorofuro[3,2-b]pyridine

[0450]

[0451] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 117 mg (0.559 mmol) of (3-(tert-butylthio)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane) gave the compound as a pale yellow solid (94 mg, 68% yield).

[0452] 1 H NMR (500 MHz, chloroform-d) δ 8.62 (d, J = 2.0 Hz, 1H), 8.17 - 8.09 (m, 3H), 7.82 (d, J = 2.1 Hz, 1H), 7.54 (dt, J = 7.7, 1.5 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H), 1.34 (s, 9H).

[0453] 13 C NMR (126 MHz, CDCl3) δ 148.52, 145.72, 145.44, 144.38, 136.95, 135.80, 133.60, 130.35, 129.12, 127.82, 127.64, 121.43, 118.84, 46.23, 31.19.

[0454] HRMS (APCI): Calcd for C 17 H 16 ClNOS [M + H] + = 318.0714; Found [M + H] + = 318.0711.

[0455] FTIR (neat), cm -1 : 2966, 2921, 2895, 2859, 1468, 1455, 1383, 1362, 1275, 1165, 1137, 1093, 1079, 992, 909, 898, 868, 806, 786, 698, 596, 516.

[0456] Preparation Example 45: tert-Butyl 4-(4-(3-(3-(tert-butylthio)phenyl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0457]

[0458] Using 84 mg (0.264 mmol) of 3-(3-(tert-butylthio)phenyl)-6-chlorofuro[3,2-b]pyridine (Preparation Example 44) and 133 mg (0.344 mmol) of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 4:1) gave the compound as a pale yellow solid (130 mg, 90% yield).

[0459] 1 H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.8 Hz, 1H), 8.22 (dt, J = 7.5, 1.5 Hz, 1H), 8.19 - 8.07 (m, 2H), 7.92 (d, J = 1.9 Hz, 1H), 7.56 (dd, J = 20.2, 8.1 Hz, 3H), 7.47 (t, J = 7.7 Hz, 1H), 7.05 (d, J = 8.3 Hz, 2H), 3.62 (t, J = 5.2 Hz, 4H), 3.23 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H), 1.35 (s, 9H).

[0460] 13 C NMR (126 MHz, CDCl3) δ 154.87, 151.07, 149.43, 145.21, 145.09, 144.36, 136.69, 135.80, 133.43, 133.12, 131.03, 129.59, 129.11, 128.36, 127.78, 121.38, 116.91, 116.09, 80.16, 49.14, 46.18, 43.64, 31.21, 28.59.

[0461] HRMS (APCI): Calcd for C 32 H 37 N3O3S [M + H] + = 544.2628; Found [M + H] + = 544.2634.

[0462] FTIR (neat), cm -1 2971, 2924, 2899, 2861, 2837, 1697, 1607, 1465, 1422, 1378, 1366, 1341, 1256, 1229, 1205, 1161, 1126, 1100, 1046, 993, 907, 812, 794, 763, 695, 534, 524.

[0463] Preparation Example 46:3-(3-(tert-Butylthio)phenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2- b]pyridine

[0464]

[0465] Using 80 mg (0.147 mmol) of tert-butyl 4-(4-(3-(3-(tert-butylthio)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 45), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 8:1) gave the compound as a pale yellow solid (55 mg, 84% yield).

[0466] 1 H NMR (500 MHz, DMSO-d6) δ 8.95 (d, J = 1.9 Hz, 1H), 8.90 (s, 1H), 8.48 (t, J = 1.8 Hz, 1H), 8.31 (d, J = 1.9 Hz, 1H), 8.27 (dt, J = 7.6, 1.6 Hz, 1H), 7.79 - 7.65 (m, 2H), 7.61 - 7.40 (m, 2H), 7.21 - 6.95 (m, 2H), 3.15 (dd, J = 6.1, 4.0 Hz, 4H), 2.98 - 2.76 (m, 4H), 1.31 (s, 9H).

[0467] 13 C NMR (126 MHz, DMSO) δ 151.24, 148.87, 146.99, 144.33, 143.14, 135.78, 134.66, 132.60, 132.35, 131.00, 128.99, 127.69, 126.83, 126.74, 119.29, 115.55, 115.45, 48.64, 45.72, 45.29, 30.71.

[0468] HRMS (APCI): Calcd for C 27 H 29 N3OS [M + H] + = 444.2104; Found [M + H] + = 444.2107.

[0469] FTIR (neat), cm -1 : 3313, 2973, 2958, 2940, 2924, 2854, 1596, 1526, 1484, 1454, 1382, 1364, 1336, 1241, 1206, 1147, 1126, 1099, 888, 836, 821, 790, 773, 695, 658, 541, 521.

[0470] Preparation Example 47: 4-(3-(Pyridin-4-yl)furo[3,2-b]pyridin-6-yl)aniline

[0471]

[0472] Using 60 mg (0.260 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 74 mg (0.338 mmol) of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 0:1) gave the compound as a pale yellow solid (71 mg, 95% yield).

[0473] 1 H NMR (500 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.91 (d, J = 1.9 Hz, 1H), 8.69 - 8.66 (m, 2H), 8.28 - 8.23 (m, 3H), 7.56 - 7.48 (m, 2H), 6.81 - 6.65 (m, 2H), 5.40 (bs, 2H).

[0474] 13 C NMR (126 MHz, DMSO) δ 150.01, 149.13, 149.06, 148.59, 144.34, 142.18, 138.07, 133.44, 127.82, 123.76, 120.68, 117.78, 115.20, 114.31.

[0475] HRMS (APCI): Calcd for C 18 H 13 N3O [M + H] + = 288.1131; Found [M + H] + = 288.1128.

[0476] FTIR (neat), cm -1 3435, 3307, 3167, 1642, 1601, 1524, 1477, 1417, 1376, 1360, 1312, 1261, 1202, 1179, 1127, 1104, 882, 827, 808, 780, 732, 670, 660, 652, 634, 531, 521.

[0477] Preparation Example 48: 6-(6-(Piperidin-1-yl)pyridin-3-yl)-3-(pyridin-4-yl)furo[3,2-b]py ridine

[0478]

[0479] Using 60 mg (0.260 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 97 mg (0.338 mmol) of 6-(piperidin-1-yl)pyridine-3-boronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 0:1) gave the compound as a pale yellow solid (71 mg, 77% yield).

[0480] 1 H NMR (500 MHz, chloroform-d) δ 8.86 (d, J = 1.9 Hz, 1H), 8.75 - 8.69 (m, 2H), 8.49 (dd, J = 2.6, 0.7 Hz, 1H), 8.27 (s, 1H), 8.10 - 8.02 (m, 2H), 7.92 (d, J = 1.9 Hz, 1H), 7.74 (dd, J = 8.9, 2.6 Hz, 1H), 6.78 (dd, J = 8.9, 0.8 Hz, 1H), 3.64 (dd, J = 5.5, 3.3 Hz, 4H), 1.69 (dd, J = 7.5, 3.5 Hz, 6H).

[0481] 13 C NMR (126 MHz, CDCl3) δ 159.08, 150.40, 149.65, 146.53, 145.05, 143.78, 138.57, 136.39, 131.51, 121.75, 121.45, 119.63, 115.84, 107.18, 46.46, 25.69, 24.87.

[0482] HRMS (APCI): Calcd for C 22 H 20 N4O [M + H] + = 357.1710; Found [M + H] + = 357.1709.

[0483] FTIR (neat), cm -1 2934, 2852, 1602, 1510, 1477, 1450, 1408, 1247, 1206, 1127, 809.

[0484] Preparation Example 49: 6-Chloro-3-(4-fluorophenyl)furo[3,2-b]pyridine

[0485]

[0486] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 78 mg (0.559 mmol) of (4-fluorophenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane) gave the compound as a pale yellow solid (70 mg, 66% yield).

[0487] 1 H NMR (500 MHz, chloroform-d) δ 8.61 (d, J = 2.0 Hz, 1H), 8.08 (s, 1H), 8.02 (dd, J = 8.8, 5.3 Hz, 2H), 7.83 (d, J = 2.0 Hz, 1H), 7.17 (t, J = 8.7 Hz, 2H).

[0488] 13 C NMR (126 MHz, chloroform-d) δ 162.74 (d, J = 247.5 Hz), 148.53, 145.37, 145.30 (d, J = 1.4 Hz), 144.35, 128.99 (d, J = 8.0 Hz), 127.88, 126.08 (d, J = 3.4 Hz), 121.16, 118.94, 116.06 (d, J = 21.6 Hz).

[0489] HRMS (APCI): Calcd for C 13 H7ClFNO [M+H] + = 248.0273; Found [M+H] + = 248.0275.

[0490] FTIR (neat), cm -1 : 3151, 3075, 1568, 1504, 1461, 1386, 1267, 1217, 1163, 1134, 1087, 1071, 967, 912, 871, 833, 798, 783, 713, 611, 585, 521, 506.

[0491] Preparation Example 50: tert-Butyl 4-(4-(3-(4-fluorophenyl)furo[3,2-b]pyridin-6-yl)phenyl)piper azine-1-carboxylate

[0492]

[0493] Using 85 mg (0.343 mmol) of 6-chloro-3-(4-fluorophenyl)furo[3,2-b]pyridine (Preparation Example 49) and 173 mg (0.446 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:1) gave the compound as a white solid (130 mg, 80% yield).

[0494] 1 H NMR (500 MHz, chloroform-d) δ 8.87 (d, J = 1.9 Hz, 1H), 8.16 - 8.01 (m, 3H), 7.93 (d, J = 1.9 Hz, 1H), 7.58 (d, J = 8.8 Hz, 2H), 7.18 (t, J = 8.7 Hz, 2H), 7.06 (d, J = 8.3 Hz, 2H), 3.66 - 3.55 (m, 4H), 3.23 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H).

[0495] 13 C NMR (126 MHz, chloroform-d) δ 162,60 (d, J = 247.2 Hz), 154.88, 151.07, 149.42, 145.12, 144.65, 144.31, 133.17, 128.96 (d, J = 7.9 Hz), 128.39, 126.74 (d, J = 3.4 Hz), 121.08, 116.95, 116.19, 115.99 (d, J = 21.6 Hz), 80.19, 49.18, 43.53, 28.61.

[0496] HRMS (APCI): Calcd for C 28 H 28 FN3O3 [M + H] + = 474.2187; Found [M + H] + = 474.2187.

[0497] FTIR (neat), cm -1 2975, 2930, 2836, 1686, 1609, 1524, 1504, 1480, 1414, 1380, 1364, 1239, 1203, 1159, 1124, 1104, 1047, 912, 844, 823, 810, 773, 585, 548, 529.

[0498] Preparation Example 51: 3-(4-Fluorophenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[0499]

[0500] Using 85 mg (0.180 mmol) of tert-butyl 4-(4-(3-(4-fluorophenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 50), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a pale yellow solid (60 mg, 90% yield).

[0501] 1 H NMR (500 MHz, DMSO-d6) δ 8.94 (d, J = 1.9 Hz, 1H), 8.83 (s, 1H), 8.36 - 8.23 (m, 3H), 7.79 - 7.66 (m, 2H), 7.35 (t, J = 8.9 Hz, 2H), 7.21 - 7.05 (m, 2H), 3.32 (dd, J = 6.5, 3.8 Hz, 4H), 3.07 (dd, J = 6.6, 3.6 Hz, 4H).

[0502] 13 C NMR (126 MHz, DMSO) δ 162.49, 160.54, 150.48, 148.77, 146.49, 144.26, 143.24, 132.19, 128.52, 128.45, 127.80, 127.45, 126.90, 126.88, 119.09, 115.85, 115.70, 115.65, 115.48, 46.86, 43.86.

[0503] HRMS (APCI): Calcd for C 23 H 20 FN3O [M + H] + = 374.1663; Found [M + H] + = 374.1663.

[0504] FTIR (neat), cm -1 : 2931, 2835, 2700, 2612, 2496, 2475, 1605, 1573, 1524, 1504, 1481, 1455, 1378, 1340, 1245, 1217, 1201, 1162, 1123, 1095, 968, 916, 890, 846, 831, 801, 652, 584, 544, 525.

[0505] Preparation Example 52: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-N,N-dimethylbenzamide

[0506]

[0507] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 108 mg (0.559 mmol) of (3-(dimethylcarbamoyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) gave a pale yellow solid compound (105 mg, 81% yield).

[0508] 1 H NMR (500 MHz, chloroform-d) δ 8.61 (d, J = 2.0 Hz, 1H), 8.13 (d, J = 8.9 Hz, 2H), 8.09 (t, J = 1.7 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.51 (t, J = 7.7 Hz, 1H), 7.41 (dt, J = 7.6, 1.4 Hz, 1H), 3.10 (d, J = 48.2 Hz, 6H).

[0509] 13 C NMR (126 MHz, CDCl3) δ 171.45, 148.55, 145.93, 145.42, 144.29, 137.12, 130.34, 129.04, 128.32, 127.89, 126.70, 125.93, 121.33, 118.94, 39.82, 35.59.

[0510] HRMS (APCI): Calcd for C 16 H 13 ClN2O2 [M+H] + = 301.0738; Found [M+H] + = 301.0741.

[0511] FTIR (neat), cm -1 : 3091, 3064, 2924, 1618, 1586, 1503, 1467, 1384, 1263, 1198, 1133, 1087, 906, 893, 869, 801, 776, 761, 746, 693, 663, 596, 523.

[0512] Preparation Example 53: tert-Butyl 4-(4-(3-(3-(dimethylcarbamoyl)phenyl)furo[3,2-b]pyr idin-6-yl)phenyl)piperazine-1-carboxylate

[0513]

[0514] Using 85 mg (0.283 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-N,N-dimethylbenzamide (Preparation Example 52) and 143 mg (0.367 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:3) gave the compound as a pale yellow solid (99 mg, 67% yield).

[0515] 1 H NMR (500 MHz, chloroform-d) δ 8.87 (d, J = 1.9 Hz, 1H), 8.21 (dt, J = 7.8, 1.4 Hz, 1H), 8.14 (s, 1H), 8.13 (t, J = 1.7 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.60 - 7.54 (m, 2H), 7.52 (t, J = 7.7 Hz, 1H), 7.40 (dt, J = 7.6, 1.4 Hz, 1H), 7.08 - 6.85 (m, 2H), 3.65 - 3.59 (m, 4H), 3.23 (t, J = 5.2 Hz, 4H), 3.15 (s, 3H), 3.06 (s, 3H), 1.50 (s, 9H).

[0516] 13 C NMR (126 MHz, CDCl3) δ 171.57, 154.86, 151.08, 149.43, 145.26, 145.16, 144.23, 137.03, 133.17, 130.99, 129.46, 128.99, 128.37, 128.34, 126.40, 125.85, 121.23, 116.87, 116.13, 80.14, 49.09, 43.56, 39.83, 35.56, 28.58.

[0517] HRMS (APCI): Calcd for C 31 H 34 N4O4 [M + H] + = 527.2653; Found [M + H] + = 527.2656.

[0518] FTIR (neat), cm -13098,2974,2926,2862,2827,1688,1604,1526,1478,1449,1426,1404,1386,1363,1261,1238,1162,1125,1104,1077,1051,1008,998,914,822,807,793,743,698,531。

[0519] Preparation Example 54: N,N-Dimethyl-3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzamide

[0520]

[0521] Using 85 mg (0.161 mmol) of tert-butyl 4-(4-(3-(3-(dimethylcarbamoyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 53), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a pale yellow solid (59 mg, 86% yield).

[0522] 1 H NMR (500 MHz, DMSO-d6) δ 8.96 (d, J = 1.9 Hz, 1H), 8.92 (s, 1H), 8.37 - 8.27 (m, 3H), 7.76 - 7.68 (m, 2H), 7.56 (t, J = 7.7 Hz, 1H), 7.38 (dt, J = 7.6, 1.4 Hz, 1H), 7.15 - 7.03 (m, 2H), 3.32 - 3.26 (m, 4H), 3.07 - 2.95 (m, 10H).

[0523] 13 C NMR (126 MHz, DMSO) δ 171.90, 169.96, 150.61, 148.85, 147.14, 144.36, 143.24, 137.04, 132.23, 130.57, 128.62, 127.78, 127.33, 127.12, 125.80, 124.80, 119.38, 115.79, 115.70, 47.14, 44.10, 21.01.

[0524] HRMS (APCI): Calcd for C 26 H 26 N4O2 [M + H] + = 427.2129; Found [M + H] + = 427.2130.

[0525] FTIR (neat), cm -1 : 2931, 2830, 2717, 2477, 1604, 1524, 1380, 1248, 1189, 1146, 1086, 919, 820, 790, 780, 745, 667, 536, 523。

[0526] Preparation Example 55: 6-Chloro-3-(furan-3-yl)furo[3,2-b]pyridine

[0527]

[0528] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 72 mg (0.645 mmol) of furan-3-ylboronic acid, the compound was prepared by the general procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 4:1) gave a pale yellow solid compound (56 mg, 59% yield).

[0529] 1 1H NMR (500 MHz, chloroform-d) δ 8.59 (d, J = 2.0 Hz, 1H), 8.37 - 8.30 (m, 1H), 7.98 (s, 1H), 7.79 (d, J = 2.0 Hz, 1H), 7.53 (t, J = 1.8 Hz, 1H), 6.75 (d, J = 1.9 Hz, 1H).

[0530] 13 13C NMR (126 MHz, CDCl3) δ 148.19, 145.31, 144.66, 144.34, 143.51, 141.18, 127.89, 118.73, 115.08, 114.19, 108.45.

[0531] HRMS (APCI): Calcd for C 11 H6ClNO2 [M + H] + = 220.0160; Found [M + H] + = 220.0161.

[0532] FTIR (neat), cm -1 : 3156, 3126, 3066, 1463, 1379, 1274, 1160, 1145, 1085, 1069, 1025, 1004, 918, 881, 870, 779, 728, 651, 602, 586, 521.

[0533] Preparation Example 56: tert-Butyl 4-(4-(3-(furan-3-yl)furo[3,2-b]pyridin-6-yl)phenyl)piper azine-1-carboxylate

[0534]

[0535] Using 78 mg (0.355 mmol) of 6-chloro-3-(furan-3-yl)furo[3,2-b]pyridine (Preparation Example 55) and 179 mg (0.462 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 9:1) gave the compound as a brown solid (116 mg, 73% yield).

[0536] 1 H NMR (500 MHz, chloroform-d) δ 8.84 (d, J = 1.9 Hz, 1H), 8.39 (t, J = 1.2 Hz, 1H), 7.98 (s, 1H), 7.88 (d, J = 1.9 Hz, 1H), 7.59 - 7.51 (m, 3H), 7.09 - 7.00 (m, 2H), 6.78 (dd, J = 1.8, 0.8 Hz, 1H), 3.74 - 3.53 (m, 4H), 3.22 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H).

[0537] 13 C NMR (126 MHz, CDCl3) δ 154.85, 151.06, 149.05, 145.05, 144.29, 144.00, 143.36, 140.98, 133.20, 129.58, 128.33, 116.86, 115.95, 114.89, 114.71, 108.58, 80.12, 49.09, 43.60, 28.58.

[0538] HRMS (APCI): Calcd for C 26 H 27 N3O4 [M + H] + = 446.2074; Found [M + H] + = 446.2073.

[0539] FTIR (neat), cm -1 2975, 2916, 2864, 2836, 1687, 1606, 1522, 1478, 1459, 1421, 1366, 1337, 1265, 1232, 1207, 1157, 1122, 1089, 1045, 1031, 998, 912, 887, 871, 825, 785, 765, 732, 592, 548, 526.

[0540] Preparation Example 57:3-(Furan-3-yl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[0541]

[0542] Using 70 mg (0.157 mmol) of tert-butyl 4-(4-(3-(furan-3-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 56), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a brown solid (33 mg, 61% yield).

[0543] 1 H NMR (500 MHz, DMSO-d6) δ 8.90 (d, J = 1.9 Hz, 1H), 8.63 (s, 1H), 8.51 - 8.41 (m, 1H), 8.26 (d, J = 1.9 Hz, 1H), 7.82 (t, J = 1.7 Hz, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.11 - 7.02 (m, 3H), 5.75 (s, DCM), 3.18 - 3.12 (m, 4H), 2.93 - 2.83 (m, 4H).

[0544] 13 C NMR (126 MHz, DMSO) δ 151.34, 148.44, 145.55, 144.28, 143.73, 143.06, 139.96, 132.52, 127.70, 126.79, 115.43, 115.41, 114.70, 113.67, 108.70, 48.90, 45.47.

[0545] HRMS (APCI): Calcd for C 21 H 19 N3O2 [M + H] + = 346.1550; Found [M + H] + = 346.1551.

[0546] FTIR (neat), cm -1 : 3243, 3084, 2949, 2833, 1605, 1522, 1478, 1446, 1377, 1339, 1236, 1204, 1154, 1133, 1078, 1067, 1027, 882, 871, 815, 792, 750, 737, 700, 591, 544, 516.

[0547] Preparation Example 58: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(pyridin-4-yl)furo[3,2-b]py ridine

[0548]

[0549] Using 50 mg (0.217 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 85 mg (0.282 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1) gave the compound as a yellow solid (55 mg, 68% yield).

[0550] 1 H NMR (500 MHz, DMSO-d6) δ 9.08 (s, 1H), 8.97 (d, J = 1.9 Hz, 1H), 8.69 (d, J = 5.2 Hz, 2H), 8.36 (d, J = 1.9 Hz, 1H), 8.30 - 8.21 (m, 2H), 7.71 (d, J = 8.5 Hz, 2H), 7.08 (d, J = 8.5 Hz, 2H), 3.23 (t, J = 5.0 Hz, 4H), 4.49 (t, J = 5.0 Hz, 4H), 2.25 (s, 3H).

[0551] 13 C NMR (126 MHz, DMSO) δ 150.79, 150.08, 149.04, 148.93, 144.63, 142.75, 137.94, 132.70, 127.77, 126.64, 120.68, 117.81, 115.85, 115.49, 54.42, 47.57, 45.68.

[0552] HRMS (APCI): Calcd for C 23 H 22 N4O [M + H] + = 371.1866; Found [M + H] + = 371.1866.

[0553] FTIR (neat), cm -1 3076, 3055, 2963, 2936, 2844, 2801, 1603, 1524, 1479, 1382, 1293, 1244, 1202, 1161, 1145, 1087, 1008, 978, 921, 815, 789, 672, 638, 526.

[0554] Preparation Example 59: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-N,N-dimethylbenzenesulfonamide

[0555]

[0556] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 174 mg (0.559 mmol) of N,N-dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 4:1) gave the compound as a white solid (112 mg, 77% yield).

[0557] 1 1H NMR (500 MHz, chloroform-d) δ 8.67 - 8.58 (m, 1H), 8.41 (s, 1H), 8.37 (d, J = 7.7 Hz, 1H), 8.22 (s, 1H), 7.92 - 7.82 (m, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 2.78 (s, 6H).

[0558] 13 13C NMR (126 MHz, CDCl3) δ 148.57, 146.24, 145.70, 143.95, 136.61, 131.32, 129.74, 128.19, 127.04, 126.08, 120.53, 119.08, 38.15.

[0559] HRMS (APCI): Calcd for C 15 H 13 ClN2O3S [M+H] + = 337.0408; Found [M+H] + = 337.0406.

[0560] FTIR (neat), cm -1 : 3069, 1387, 1333, 1311, 1269, 1159, 1137, 1096, 986, 958, 917, 873, 835, 801, 784, 715, 694, 599, 578, 565, 488.

[0561] Preparation Example 60: tert-Butyl 4-(4-(3-(3-(N,N-dimethylsulfamoyl)phenyl)furo[3,2-b] pyridin-6-yl)phenyl)piperazine-1-carboxylate

[0562]

[0563] Using 100 mg (0.297 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-N,N-dimethylbenzenesulfonamide (Preparation Example 59) and 150 mg (0.386 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) gave the compound as a white solid (124 mg, 74% yield).

[0564] 1 H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.9 Hz, 1H), 8.47 (dt, J = 7.8, 1.4 Hz, 1H), 8.44 (t, J = 1.8 Hz, 1H), 8.21 (s, 1H), 7.94 (d, J = 1.9 Hz, 1H), 7.76 (dt, J = 7.8, 1.5 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.62 - 7.53 (m, 2H), 7.06 (d, J = 8.3 Hz, 2H), 3.62 (t, J = 5.2 Hz, 4H), 3.24 (t, J = 5.2 Hz, 4H), 2.79 (s, 6H), 1.50 (s, 9H).

[0565] 13 C NMR (126 MHz, CDCl3) δ 154.87, 149.49, 145.56, 145.41, 143.89, 136.45, 133.49, 132.01, 131.44, 129.70, 128.38, 126.76, 126.05, 120.47, 116.92, 116.26, 80.20, 49.12, 43.53, 38.17, 28.58.

[0566] HRMS (APCI): Calcd for C 30 H 34 N4O5S [M + H] + = 563.2323; Found [M + H] + = 563.2321.

[0567] FTIR (neat), cm -1 2973, 2926, 2856, 1692, 1606, 1480, 1422, 1383, 1366, 1341, 1234, 1160, 1126, 714, 694, 582.

[0568] Preparation Example 61: N,N-Dimethyl-3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzenesulfonamide

[0569]

[0570] Using 90 mg (0.160 mmol) of tert-butyl 4-(4-(3-(3-(N,N-dimethylsulfamoyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 60), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 4:1) gave the compound as a pale yellow solid (69 mg, 93% yield).

[0571] 1 H NMR (500 MHz, DMSO-d6) δ 9.05 (s, 1H), 9.00 (d, J = 1.9 Hz, 1H), 8.73 (t, J = 1.9 Hz, 1H), 8.54 (dt, J = 7.7, 1.6 Hz, 1H), 8.38 (d, J = 1.9 Hz, 1H), 7.87 - 7.69 (m, 5H), 7.12 (d, J = 8.9 Hz, 2H), 3.40 (dd, J = 6.7, 3.7 Hz, 4H), 3.17 (dd, J = 6.5, 3.8 Hz, 4H), 2.69 (s, 6H).

[0572] 13 C NMR (126 MHz, DMSO) δ 148.90, 147.91, 144.61, 143.05, 135.52, 132.34, 131.69, 130.61, 129.76, 127.88, 126.35, 125.00, 118.60, 116.04, 115.90, 45.84, 43.10, 37.61.

[0573] HRMS (APCI): Calcd for C 25 H 26 N4O3S [M + H] + = 463.1798; Found [M + H] + = 463.1794.

[0574] FTIR (neat), cm -1 : 2927, 2841, 2726, 2500, 2482, 1605, 1336, 1159, 1094, 953, 822, 803, 782, 714, 693, 581, 544, 492.

[0575] Preparation Example 62: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)benzenesulfonamide

[0576]

[0577] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 158 mg (0.559 mmol) of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:2) gave the compound as a white solid (110 mg, 83% yield).

[0578] 1 1H NMR (500 MHz, DMSO-d6) δ 9.01 (s, 1H), 8.73 (d, J = 2.1 Hz, 1H), 8.70 (t, J = 1.8 Hz, 1H), 8.46 (d, J = 2.1 Hz, 1H), 8.35 (dt, J = 7.8, 1.4 Hz, 1H), 7.85 (ddd, J = 7.8, 1.9, 1.1 Hz, 1H), 7.71 (t, J = 7.8 Hz, 1H), 7.42 (s, 2H).

[0579] 13 13C NMR (126 MHz, DMSO) δ 148.60, 147.98, 144.95, 144.78, 143.47, 130.49, 129.59, 129.46, 126.99, 124.99, 123.47, 119.60, 119.04.

[0580] HRMS (APCI): Calcd for C 13 H9ClN2O3S [M+H] + = 309.0095; Found [M+H] + = 309.0093.

[0581] FTIR (neat), cm -1 : 3319, 3232, 3073, 1385, 1326, 1315, 1273, 1161, 1138, 1101, 1076, 999, 886, 792, 771, 705, 681, 649, 597, 559, 525, 493.

[0582] Preparation Example 63: tert-Butyl 4-(4-(3-(3-sulfamoylphenyl)furo[3,2-b]pyridin-6-yl)ben yl)piperazine-1-carboxylate

[0583]

[0584] Using 100 mg (0.324 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzenesulfonamide (Preparation Example 62) and 164 mg (0.421 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:4) gave the compound as a white solid (102 mg, 59% yield).

[0585] 1 H NMR (500 MHz, DMSO-d6) δ 8.97 (d, J = 1.9 Hz, 1H), 8.94 (s, 1H), 8.80 (t, J = 1.8 Hz, 1H), 8.42 (dt, J = 7.7, 1.4 Hz, 1H), 8.35 (d, J = 1.9 Hz, 1H), 7.86 - 7.80 (m, 1H), 7.77 - 7.68 (m, 3H), 7.41 (s, 2H), 7.13 - 7.05 (m, 2H), 3.49 (dd, J = 6.6, 3.8 Hz, 4H), 3.25 - 3.14 (m, 4H), 1.43 (s, 9H).

[0586] 13 C NMR (126 MHz, DMSO) δ 153.82, 150.63, 148.88, 147.43, 144.74, 144.46, 142.98, 132.45, 131.16, 129.48, 129.36, 127.82, 127.32, 124.72, 123.43, 119.00, 116.04, 115.81, 78.96, 47.84, 28.03.

[0587] HRMS (APCI): Calcd for C 28 H 30 N4O5S [M + H] + = 535.2010; Found [M + H] + = 535.2006.

[0588] FTIR (neat), cm -1 3274, 2975, 2818, 1699, 1606, 1525, 1486, 1416, 1335, 1263, 1232, 1199, 1159, 1125, 1087, 988, 919, 816, 799, 690, 588, 541, 523, 506.

[0589] Preparation Example 64: 3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzenesulfonamide

[0590]

[0591] Using 90 mg (0.168 mmol) of tert-butyl 4-(4-(3-(3-sulfamoylphenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 63), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a pale yellow solid (44 mg, 60% yield).

[0592] 1 H NMR (500 MHz, DMSO-d6) δ 8.97 (d, J = 1.9 Hz, 1H), 8.93 (s, 1H), 8.79 (d, J = 1.9 Hz, 1H), 8.42 (d, J = 7.7 Hz, 1H), 8.34 (d, J = 1.9 Hz, 1H), 7.87 - 7.81 (m, 1H), 7.71 (dt, J = 7.9, 3.5 Hz, 3H), 7.41 (s, 2H), 7.06 (d, J = 8.5 Hz, 2H), 3.14 (t, J = 5.0 Hz, 4H), 2.87 (t, J = 5.0 Hz, 4H).

[0593] 13 C NMR (126 MHz, DMSO) δ 151.37, 148.90, 147.34, 144.73, 144.40, 142.87, 132.58, 131.18, 129.48, 129.35, 127.73, 126.61, 124.70, 123.42, 119.00, 115.67, 115.42, 48.82, 45.42.

[0594] HRMS (APCI): Calcd for C 23 H 22 N4O3S [M + H] + = 435.1485; Found [M + H] + = 435.1489.

[0595] FTIR (neat), cm -1 : 3325, 3304, 2826, 1603, 1527, 1484, 1380, 1325, 1308, 1240, 1205, 1148, 1118, 1101, 1088, 1004, 922, 890, 878, 832, 815, 794, 686, 659, 591, 548, 533, 523, 513, 474.

[0596] Preparation Example 64: 6-Chloro-3-(4-isopropylphenyl)furo[3,2-b]pyridine

[0597]

[0598] Using 108 mg (0.465 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 99 mg (0.604 mmol) of (4-isopropylphenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane) gave a pale yellow solid compound (110 mg, 83% yield).

[0599] 1 H NMR (500 MHz, chloroform-d) δ 8.61 (d, J = 2.1 Hz, 1H), 8.07 (s, 1H), 7.92 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 2.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 2.96 (p, J = 6.9 Hz, 1H), 1.29 (d, J = 6.9 Hz, 6H).

[0600] 13 C NMR (126 MHz, CDCl3) δ 149.04, 148.50, 145.30, 145.26, 144.71, 127.62, 127.37, 127.34, 127.15, 122.11, 118.78, 34.16, 24.09.

[0601] HRMS (APCI): Calcd for C 16 H 14 ClNO [M + H] + = 272.0837; Found [M + H] + = 272.0839.

[0602] FTIR (neat), cm -1 : 2955, 2928, 2897, 2866, 1578, 1506, 1461, 1384, 1335, 1281, 1264, 1222, 1136, 1091, 1072, 1052, 1018, 967, 929, 909, 870, 850, 831, 810, 784, 761, 617, 594, 544, 520.

[0603] Preparation Example 66: tert-Butyl 4-(4-(3-(4-isopropylphenyl)furo[3,2-b]pyridin-6-yl)phenyl) piperazine-1-carboxylate

[0604]

[0605] Using 102 mg (0.375 mmol) of 6-chloro-3-(4-isopropylphenyl)furo[3,2-b]pyridine (Preparation Example 65) and 189 mg (0.488 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 9:1) gave the compound as a pale yellow solid (123 mg, 66% yield).

[0606] 1 H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.9 Hz, 1H), 8.08 (s, 1H), 8.04 - 7.95 (m, 2H), 7.91 (d, J = 1.9 Hz, 1H), 7.61 - 7.54 (m, 2H), 7.40 - 7.32 (m, 2H), 7.11 - 6.99 (m, 2H), 3.68 - 3.57 (m, 4H), 3.23 (t, J = 5.2 Hz, 4H), 2.97 (p, J = 6.9 Hz, 1H), 1.50 (s, 9H), 1.30 (d, J = 6.9 Hz, 6H).

[0607] 13 C NMR (126 MHz, CDCl3) δ 154.88, 149.38, 148.70, 145.02, 144.69, 144.67, 132.93, 128.37, 128.01, 127.36, 127.11, 122.03, 116.95, 116.09, 80.16, 49.20, 43.59, 34.17, 28.60, 24.12.

[0608] HRMS (APCI): Calcd for C 31 H 35 N3O3 [M + H] + = 498.2751; Found [M + H] + = 498.2750.

[0609] FTIR (neat), cm -1 2958, 2930, 2867, 2813, 2362, 2325, 1702, 1681, 1608, 1521, 1477, 1463, 1415, 1376, 1362, 1335, 1282, 1264, 1248, 1229, 1213, 1168, 1134, 1120, 1085, 1058, 1040, 968, 910, 892, 861, 829, 796, 787, 768, 558, 544.

[0610] Preparation Example 67: 3-(4-Isopropylphenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[0611]

[0612] Using 90 mg (0.181 mmol) of tert-butyl 4-(4-(3-(4-isopropylphenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 66), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1) gave the compound as a yellow solid (63 mg, 88% yield).

[0613] 1 H NMR (500 MHz, DMSO-d6) δ 8.92 (d, J = 2.0 Hz, 1H), 8.75 (s, 1H), 8.27 (d, J = 1.9 Hz, 1H), 8.16 (d, J = 8.3 Hz, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.37 (d, J = 8.2 Hz, 2H), 7.05 (d, J = 8.9 Hz, 2H), 3.22 - 3.10 (m, 4H), 2.94 (p, J = 6.9 Hz, 1H), 2.90 - 2.83 (m, 4H), 1.25 (d, J = 6.9 Hz, 6H).

[0614] 13 C NMR (126 MHz, DMSO) δ 151.32, 148.78, 147.79, 146.08, 144.12, 143.42, 132.19, 127.88, 127.67, 126.78, 126.57, 126.51, 120.09, 115.43, 115.42, 48.87, 45.46, 33.22, 23.78.

[0615] HRMS (APCI): Calcd for C 26 H 27 N3O [M + H] + = 398.2227; Found [M + H] + = 398.2231.

[0616] FTIR (neat), cm -1 : 3271, 3028, 2956, 2818, 2753, 1607, 1521, 1476, 1452, 1379, 1335, 1235, 1191, 1151, 1124, 1092, 967, 888, 817, 786, 746, 540.

[0617] Preparation Example 68:6-Chloro-3-(3-(methoxymethyl)phenyl)furo[3,2-b]pyridine

[0618]

[0619] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 93 mg (0.559 mmol) of (3-(methoxymethyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1) gave the compound as a pale yellow solid (102 mg, 87% yield).

[0620] 1 1H NMR (500 MHz, chloroform-d) δ 8.62 (d, J = 2.1 Hz, 1H), 8.12 (s, 1H), 8.00 (dt, J = 7.7, 1.4 Hz, 1H), 7.96 (dt, J = 1.8, 0.8 Hz, 1H), 7.82 (d, J = 2.1 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.38 - 7.32 (m, 1H), 4.55 (s, 2H), 3.44 (s, 3H).

[0621] 13 13C NMR (126 MHz, CDCl3) δ 148.52, 145.76, 145.32, 144.51, 139.09, 130.12, 129.14, 127.71, 127.45, 126.63, 126.36, 121.89, 118.82, 74.75, 58.37.

[0622] HRMS (APCI): Calcd for C 15 H 12 ClNO2 [M + H] + = 274.0629; Found [M + H] + = 274.0626.

[0623] FTIR (neat), cm -1 : 3061, 3013, 2937, 2829, 1469, 1379, 1200, 1129, 1104, 1077, 1016, 964, 908, 893, 870, 786, 691, 595, 524.

[0624] Preparation Example 69: tert-Butyl 4-(4-(3-(3-(methoxymethyl)phenyl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0625]

[0626] Using 90 mg (0.329 mmol) of 6-chloro-3-(3-(methoxymethyl)phenyl)furo[3,2-b]pyridine (Preparation Example 68) and 166 mg (0.427 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 3:1) gave the compound as a yellow solid (112 mg, 68% yield).

[0627] 1 H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.9 Hz, 1H), 8.13 (s, 1H), 8.08 (dt, J = 7.7, 1.5 Hz, 1H), 8.01 (t, J = 1.8 Hz, 1H), 7.92 (dd, J = 1.9, 1.0 Hz, 1H), 7.62 - 7.55 (m, 2H), 7.48 (t, J = 7.7 Hz, 1H), 7.35 (dt, J = 7.8, 1.4 Hz, 1H), 7.04 (d, J = 8.4 Hz, 2H), 4.57 (s, 2H), 3.74 - 3.52 (m, 4H), 3.44 (s, 3H), 3.23 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H).

[0628] 13 C NMR (126 MHz, CDCl3) δ 154.87, 151.08, 149.42, 145.12, 145.10, 144.49, 138.99, 133.01, 130.79, 129.60, 129.12, 128.35, 127.19, 126.68, 126.38, 121.82, 116.89, 116.07, 80.14, 74.83, 58.34, 49.12, 43.59, 28.59, 27.07.

[0629] HRMS (APCI): Calcd for C 30 H 33 N3O4 [M + H] + = 500.2544; Found [M + H] + = 500.2540.

[0630] FTIR (neat), cm -12975,2927,2864,2817,1682,1605,1524,1480,1455,1421,1375,1364,1289,1248,1232,1197,1161,1117,1102,1045,1022,998,911,887,827,788,773,696,670,540。

[0631] Preparation Example 70: 3-(3-(Methoxymethyl)phenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2- b]pyridine

[0632]

[0633] Using 90 mg (0.180 mmol) of tert-butyl 4-(4-(3-(3-(methoxymethyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 69), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a yellow solid (44 mg, 61% yield).

[0634] 1 H NMR (500 MHz, DMSO-d6) δ 8.95 (d, J = 1.9 Hz, 1H), 8.83 (s, 1H), 8.30 (d, J = 1.9 Hz, 1H), 8.22 (s, 1H), 8.18 (d, J = 7.8 Hz, 1H), 7.76 - 7.63 (m, 2H), 7.48 (t, J = 7.7 Hz, 1H), 7.32 (dt, J = 7.9, 1.3 Hz, 1H), 7.12 - 7.02 (m, 2H), 4.50 (s, 2H), 3.35 (s, 3H), 3.23 - 3.11 (m, 4H), 2.91 - 2.82 (m, 4H).

[0635] 13 C NMR (126 MHz, DMSO) δ 151.09, 148.84, 146.68, 144.24, 143.32, 138.71, 132.23, 130.42, 128.56, 127.71, 126.95, 126.77, 125.67, 125.64, 119.96, 115.53, 73.68, 57.54, 48.33, 45.03, 39.52.

[0636] HRMS (APCI): Calcd for C 25 H 25 N3O2 [M + H] + = 400.2020; Found [M + H]+ = 400.2023.

[0637] FTIR (neat), cm -1 : 2943, 2923, 2813, 1605, 1523, 1482, 1450, 1375, 1235, 1180, 1099, 885, 816, 790, 695, 540.

[0638] Preparation Example 71: 6-Chloro-3-(3-(trifluoromethyl)phenyl)furo[3,2-b]pyridine

[0639]

[0640] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 106 mg (0.559 mmol) of (3-(trifluoromethyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1) gave the compound as a white solid (125 mg, 98% yield).

[0641] 1 H NMR (500 MHz, chloroform-d) δ 8.63 (d, J = 2.0 Hz, 1H), 8.34 - 8.23 (m, 2H), 8.17 (s, 1H), 7.84 (d, J = 2.0 Hz, 1H), 7.70 - 7.56 (m, 2H).

[0642] 13 C 13 C NMR (126 MHz, chloroform-d) δ 148.56, 146.03, 145.63, 144.02, 131.46 (q, J = 32.3 Hz), 130.93, 130.59 - 130.14 (m), 129.50, 128.11, 127.26, 124.75 (q, J = 3.9 Hz), 124.25 (q, J = 272.4 Hz), 123.85 (q, J = 3.8 Hz), 120.82, 119.01.

[0643] HRMS (APCI): Calcd for C 14 H7ClF3NO [M+H] + = 298.0241; Found [M+H] + = 298.0244.

[0644] FTIR (neat), cm -1 : 1387, 1327, 1167, 1128, 1099, 1075, 914, 799, 697.

[0645] Preparation Example 72: tert-Butyl 4-(4-(3-(3-(trifluoromethyl)phenyl)furo[3,2-b]pyridin-6-yl) phenyl)piperazine-1-carboxylate

[0646]

[0647] Using 98 mg (0.329 mmol) of 6-chloro-3-(3-(trifluoromethyl)phenyl)furo[3,2-b]pyridine (Preparation Example 71) and 166 mg (0.427 mmol) of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:2) gave the compound as a yellow solid (114 mg, 66% yield).

[0648] 1 H NMR (500 MHz, CDCl₃) δ 8.90 (d, J = 1.9 Hz, 1H), 8.36 (ddd, J = 5.0, 3.1, 1.6 Hz, 1H), 8.34 (s, 1H), 8.18 (s, 1H), 7.94 (d, J = 1.9 Hz, 1H), 7.61 (dd, J = 5.0, 1.3 Hz, 2H), 7.61 - 7.55 (m, 2H), 7.05 (d, J = 8.8 Hz, 1H), 3.65 - 3.59 (m, 4H), 3.24 (t, J = 5.2 Hz, 4H), 1.50 (s, 9H).

[0649] 13 C NMR (126 MHz, CDCl₃) δ 154.88, 151.15, 149.48, 145.37, 144.00, 136.33, 133.40, 131.61, 131.37 (q, J = 32.3 Hz), 130.49, 129.46, 129.37, 128.37, 127.42, 125.44 - 123.13 (m), 120.77, 116.89, 116.20, 80.17, 49.09, 43.66, 28.59.

[0650] HRMS (APCI): Calcd for C 29 H 28 F₃N₃O₃ [M + H] + = 524.2156; Found [M + H] + = 524.2161.

[0651] FTIR (neat), cm -12978,2930,2817,1683,1607,1424,1380,1365,1334,1315,1251,1233,1161,1122,1089,1073,1047,1000,909,817,800,768,697,680,547,528。

[0652] Preparation Example 73: 6-(4-(Piperazin-1-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)furo[3,2-b] pyridine

[0653]

[0654] Using 90 mg (0.172 mmol) of tert-butyl 4-(4-(3-(3-(trifluoromethyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 72), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a yellow solid (68 mg, 93% yield).

[0655] 1 H NMR (500 MHz, DMSO-d6) δ 9.02 (s, 1H), 8.98 (d, J = 1.9 Hz, 1H), 8.72 (t, J = 1.6 Hz, 1H), 8.57 - 8.51 (m, 1H), 8.33 (d, J = 1.9 Hz, 1H), 7.82 - 7.67 (m, 4H), 7.06 (d, J = 8.9 Hz, 2H), 3.22 - 3.15 (m, 4H), 2.97 - 2.88 (m, 4H).

[0656] 13 C NMR (126 MHz, DMSO-d6) δ 151.10, 148.92, 147.68, 144.51, 142.88, 132.51, 131.68, 130.13, 129.75, 129.55 (q, J = 31.5 Hz), 127.74, 126.81, 125.32, 123.34 (dq, J = 155.7, 3.8 Hz), 123.15, 118.56, 115.72, 115.53, 48.21, 44.94.

[0657] HRMS (APCI): Calcd for C 24 H 20 F3N3O [M + H] + = 424.1631; Found [M + H] + = 424.1628.

[0658] FTIR (neat), cm -1 : 1604, 1523, 1482, 1378, 1334, 1314, 1239, 1198, 1164, 1114, 1089, 1074, 889, 822, 796, 697, 677, 524。

[0659] Preparation Example 74: 5-Chloro-2-iodo-6-methylpyridin-3-ol

[0660]

[0661] Iodine (884 mg, 3.48 mmol) was added to a mixture of 5-chloro-6-methylpyridin-3-ol (500 mg, 3.48 mol) and Na2CO3 (775 mg, 7.31 mmol) in H2O (10 mL). The resulting mixture was stirred at 25 °C under N2 for 2 h. The mixture was neutralized with 1 M aqueous HCl (11 mL) and extracted with EtOAc (3 × 20 mL). The combined organic extracts were washed with brine (20 mL), dried over MgSO4, filtered, and the solvent was evaporated in vacuo. A brown solid product (895 mg, 95% yield) was obtained.

[0662] 1 1H NMR (500 MHz, DMSO-d6) δ 11.02 (s, 1H), 7.14 (s, 1H), 2.39 (s, 3H).

[0663] 13 13C NMR (126 MHz, DMSO) δ 152.74, 146.37, 129.68, 121.24, 107.10, 20.65.

[0664] HRMS (APCI): Calcd for C6H5ClINO [M+H] + = 269.9177; Found [M+H] + = 269.9175.

[0665] FTIR (neat), cm -1 : 2957, 2922, 2851, 1541, 1464, 1400, 1370, 1321, 1265, 1223, 1202, 1089, 1002, 871, 779, 748, 708, 483.

[0666] Preparation Example 75: 6-Chloro-5-methyl-2-(trimethylsilyl)furo[3,2-b]pyridine

[0667]

[0668] To a degassed solution of 5-chloro-2-iodo-6-methylpyridin-3-ol (Preparation Example 74, 800 mg, 2.97 mmol) in dioxane (10 mL) and TEA (4 mL) was added ethynyltrimethylsilane (0.549 mL, 3.86 mmol), PdCl2(PPh3)2 (63 mg, 0.089 mmol) and CuI (34 mg, 0.178 mmol), and the resulting mixture was stirred at 45 °C for 2 h. The solvent was evaporated in vacuo and the residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1). A beige solid product (504 mg, 71% yield) was obtained.

[0669] 1 1H NMR (500 MHz, chloroform-d) δ 7.74 (d, J = 1.0 Hz, 1H), 7.05 (d, J = 1.0 Hz, 1H), 2.70 (s, 3H), 0.36 (s, 9H).

[0670] 13 13C NMR (126 MHz, CDCl3) δ 169.91, 151.73, 149.66, 146.23, 126.70, 118.92, 116.75, 23.01, -1.90.

[0671] HRMS (APCI): Calcd for C 11 H 14 ClNOSi [M+H] + = 240.0606, found [M+H] + = 240.0609.

[0672] FTIR (neat), cm -1 : 3060, 2957, 2897, 1399, 1271, 1249, 1060, 995, 907, 884, 824, 750, 697, 627, 506.

[0673] Preparation Example 76: 6-Chloro-5-methylfuro[3,2-b]pyridine

[0674]

[0675] To a solution of 6-chloro-5-methyl-2-(trimethylsilyl)furo[3,2-b]pyridine (Preparation Example 75, 480 mg, 2.0 mmol) in methanol (10 mL) was added KF (349 mg, 6.0 mmol), and the resulting mixture was stirred at 48 °C for 24 h. The solvent was evaporated in vacuo and the residue was purified by column chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1). A white solid product (186 mg, 55%) was obtained.

[0676] 1 1H NMR (500 MHz, chloroform-d) δ 7.78 (d, J = 2.3 Hz, 1H), 7.76 (s, 1H), 6.90 (dd, J = 2.3, 1.0 Hz, 1H), 2.70 (s, 3H).

[0677] 13 13C NMR (126 MHz, CDCl3) δ 152.32, 149.59, 146.56, 145.34, 126.87, 119.23, 107.94, 23.00.

[0678] HRMS (APCI): Calcd for C8H6ClNO [M+H]+ + = 168.0211, found = 168.0208.

[0679] FTIR (neat), cm -1 : 3148, 3121, 3066, 2925, 1404, 1373, 1314, 1268, 1124, 1025, 1000, 989, 883, 813, 777, 756, 739, 650, 581, 467.

[0680] Preparation Example 77: 2,3-Dibromo-6-chloro-5-methyl-2,3-dihydrofuro[3,2-b]pyridine

[0681]

[0682] Bromine (0.171 mL, 3.33 mmol) was slowly added to a stirred solution of 6-chloro-5-methylfuro[3,2-b]pyridine (Preparation Example 76, 186 mg, 1.11 mmol) in DCM (10 mL) at 25 °C. The resulting mixture was stirred for 3 h. Then, an aqueous solution of Na2S2O5 (1 g) in water (30 mL) was added and the resulting mixture was extracted with DCM (3 × 30 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The residue was purified by column chromatography (cyclohexane / EtOAc, gradient 1:0 to 4:1). A white solid product was obtained (258 mg, 71%).

[0683] 1 1H NMR (500 MHz, chloroform-d) δ 7.36 (s, 1H), 6.86 (s, 1H), 5.64 (d, J = 0.6 Hz, 1H), 2.63 (s, 3H).

[0684] 1313C NMR (126 MHz, CDCl3) δ 152.83, 149.64, 145.42, 132.89, 120.71, 89.12, 51.25, 22.59.

[0685] HRMS (APCI): Calcd for C8H6Br2ClNO [M+H] + = 325.8577, found = 325.8573.

[0686] FTIR (neat), cm -1 : 3129, 3071, 3027, 2987, 1595, 1419, 1292, 1236, 1211, 1174, 1150, 1131, 1018, 983, 946, 879, 781, 770, 711, 652, 566, 548, 469, 417.

[0687] Preparation Example 78: 3-Bromo-6-chloro-5-methylfuro[3,2-b]pyridine

[0688]

[0689] DBU (0.361 mL, 2.42 mmol) was added to a solution of 2,3-dibromo-6-chloro-5-methyl-2,3-dihydrofuro[3,2-b]pyridine (Preparation Example 77, 240 mg, 0.733 mmol) in toluene (10 mL). The resulting mixture was stirred at 80 °C for 1 h. The solvent was evaporated and the residue was purified by column chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1). A white solid product (158 mg, 87% yield) was obtained.

[0690] 1 1H NMR (500 MHz, chloroform-d) δ 7.84 (s, 1H), 7.79 (s, 1H), 2.76 (s, 3H).

[0691] 13 13C NMR (126 MHz, CDCl3) δ 153.83, 147.00, 146.21, 142.77, 128.33, 119.73, 99.32, 23.19.

[0692] HRMS (APCI): Calcd for C8H5BrClNO [M+H] + = 245.9316, found = 245.9314.

[0693] FTIR (neat), cm -1: 3098, 3037, 1401, 1292, 1265, 1078, 1037, 988, 949, 874, 859, 813, 761, 754, 574, 469。

[0694] Preparation Example 79: 6-Chloro-5-methyl-3-(pyridin-4-yl)furo[3,2-b]pyridine

[0695]

[0696] Using 100 mg (0.406 mmol) of 3-bromo-6-chloro-5-methylfuro[3,2-b]pyridine (Preparation Example 78) and 65 mg (0.527 mmol) of pyridin-4-ylboronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 23:77) gave the compound as a beige solid (23 mg, 23% yield).

[0697] 1 H NMR (500 MHz, chloroform-d) δ 8.82 - 8.59 (m, 2H), 8.20 (s, 1H), 8.07 - 7.97 (m, 2H), 7.80 (s, 1H), 2.76 (s, 3H).

[0698] 13 C NMR (126 MHz, CDCl3) δ 153.19, 150.45, 147.63, 146.80, 143.08, 138.11, 127.64, 121.26, 119.46, 119.25, 23.37.

[0699] HRMS (APCI): Calcd for C 13 H9ClN2O [M+H] + = 245.0476; Found [M+H] + = 245.0474.

[0700] FTIR (neat), cm -1 : 3092, 3073, 3028, 2923, 1610, 1578, 1403, 1246, 1223, 1138, 1084, 1020, 992, 886, 811, 768, 755, 700, 684, 655, 600, 520, 469.

[0701] Preparation Example 80: 5-Methyl-6-(4-(4-methylpiperazin-1-yl)phenyl)-3-(pyridin-4-yl)furo [3,2-b]pyridine

[0702]

[0703] Using 22 mg (0.090 mmol) of 6-chloro-5-methyl-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 79) and 35 mg (0.117 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0% to 17:3) gave the compound as a white solid (22 mg, 64% yield).

[0704] 1 H NMR (500 MHz, DMSO-d6) δ 9.04 (s, 1H), 8.74 - 8.65 (m, 2H), 8.31 - 8.24 (m, 2H), 7.90 (s, 1H), 7.32 (d, J = 8.7 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 3.22 (t, J = 5.1 Hz, 4H), 2.61 (s, 3H).

[0705] 13 C NMR (126 MHz, DMSO) δ 152.71, 150.19, 150.05, 148.74, 147.44, 142.38, 138.17, 133.26, 129.92, 129.37, 120.63, 119.59, 117.48, 114.88, 54.52, 47.67, 45.67, 23.93.

[0706] HRMS (APCI): Calcd for C 24 H 24 N4O [M + H] + = 385.2023; Found [M + H] + = 385.2025.

[0707] FTIR (neat), cm -1 3071, 3054, 2962, 2935, 2793, 1605, 1517, 1450, 1415, 1396, 1373, 1290, 1239, 1216, 1195, 1151, 1141, 1124, 1101, 983, 921, 890, 834, 823, 794, 775, 737, 671, 643, 633, 608, 550, 525.

[0708] Preparation Example 81: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(3-nitrophenyl)furo[3,2-b] pyridine

[0709]

[0710] Using 300 mg (1.090 mmol) of 6-chloro-3-(3-nitrophenyl)furo[3,2-b]pyridine (Preparation Example 38) and 429 mg (1.420 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 19:1) gave the compound as a yellow solid (367 mg, 81% yield).

[0711] 1 H NMR (500 MHz, chloroform-d) δ 8.95 (t, J = 2.0 Hz, 1H), 8.91 (d, J = 1.9 Hz, 1H), 8.55 (dt, J = 7.8, 1.3 Hz, 1H), 8.24 (s, 1H), 8.20 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.95 (d, J = 1.9 Hz, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.63 - 7.54 (m, 2H), 7.10 - 7.01 (m, 2H), 3.37 - 3.26 (m, 4H), 2.66 - 2.57 (m, 4H), 2.38 (s, 3H).

[0712] 13 C NMR (126 MHz, CDCl3) δ 151.30, 149.58, 148.88, 145.61, 145.52, 143.55, 133.81, 133.04, 132.62, 129.93, 128.51, 128.30, 122.43, 121.81, 119.97, 116.32, 116.22, 55.14, 48.72, 46.27.

[0713] HRMS (APCI): Calcd for C 24 H 22 N4O3 [M+H] + = 415.1765; Found [M+H] + = 415.1767.

[0714] FTIR (neat), cm -1 3078, 2942, 2843, 2794, 1606, 1520, 1482, 1448, 1379, 1340, 1293, 1240, 1203, 1102, 1009, 818, 803, 778, 736, 697, 679, 527.

[0715] Preparation Example 82: 3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzamine

[0716]

[0717] To a degassed heterogeneous mixture of Pd / C (10.0 mg) in EtOH (5 mL) was added 6-(4-(4-methylpiperazin-1-yl)phenyl)-3-(3-nitrophenyl)furo[3,2-b]pyridine (Preparation Example 81, 300 mg, 0.724 mmol), and the resulting mixture was stirred under a hydrogen atmosphere at 25 °C for 3 hours. Then, the reaction mixture was filtered through a syringe filter ( XtraPTFE-20 / 25 0.25 μm), the solvent was evaporated in vacuo, and the residue was purified by flash chromatography (DCM / MeOH, gradient from 1:0 to 19:1). A pale yellow solid product (130 mg, 47% yield) was obtained.

[0718] 1 H NMR (500 MHz, DMSO-d6) δ 8.89 (d, J = 1.9 Hz, 1H), 8.63 (s, 1H), 8.26 (d, J = 1.9 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.48 (t, J = 2.0 Hz, 1H), 7.29 (dt, J = 7.6, 1.3 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 7.09 - 7.04 (m, 2H), 6.58 (ddd, J = 8.0, 2.4, 1.0 Hz, 1H), 5.14 (s, 2H), 3.26 - 3.17 (m, 5H), 2.47 (t, J = 5.1 Hz, 5H), 2.24 (s, 3H).

[0719] 13 C NMR (126 MHz, DMSO) δ 150.70, 148.79, 148.75, 146.08, 143.96, 143.55, 132.06, 130.70, 129.03, 127.70, 126.98, 120.87, 115.52, 115.42, 114.42, 113.37, 112.21, 54.46, 47.66, 45.73.

[0720] HRMS (APCI): Calcd for C 24 H 24 N4O [M + H] + = 385.2023; Found [M + H] + = 385.2026.

[0721] FTIR (neat), cm -1: 2937, 2842, 2794, 1604, 1523, 1486, 1448, 1379, 1292, 1235, 1192, 1139, 1098, 1001, 918, 817, 785, 692, 671, 543, 522, 456。

[0722] Preparation Example 83: Ethyl (3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)phenyl)carbamate

[0723]

[0724] Ethyl chloroformate (0.022 mL, 0.234 mmol) was added to a mixture of 3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)aniline (Preparation Example 82, 60 mg, 0.156 mmol) and TEA (0.043 mL, 0.312 mmol) in DCM (5 mL), and the resulting mixture was stirred at 25 °C for 2 h. Then, the reaction mixture was diluted with water (3 mL) and extracted with DCM (3 × 5 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1). A white solid product (52 mg, 73% yield) was obtained.

[0725] 1 1H NMR (500 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.91 (d, J = 1.9 Hz, 1H), 8.69 (s, 1H), 8.32 (t, J = 1.9 Hz, 1H), 8.29 (d, J = 1.9 Hz, 1H), 7.81 (dt, J = 7.5, 1.5 Hz, 1H), 7.72 - 7.66 (m, 2H), 7.44 (dt, J = 8.5, 1.5 Hz, 1H), 7.39 (t, J = 7.8 Hz, 1H), 7.10 - 7.04 (m, 2H), 4.16 (q, J = 7.1 Hz, 2H), 3.25 - 3.21 (m, 4H), 2.48 (t, J = 5.1 Hz, 4H), 2.24 (s, 3H), 1.27 (t, J = 7.1 Hz, 3H).

[0726] 1313C NMR (126 MHz, DMSO) δ 153.62, 150.72, 148.79, 146.42, 144.17, 143.27, 139.50, 132.27, 130.74, 128.92, 127.72, 126.89, 121.03, 120.36, 117.94, 116.93, 115.51, 60.08, 54.44, 47.63, 45.71, 14.50.

[0727] HRMS (APCI): Calcd for C 27 H 28 N4O3 [M+H] + = 457.2234; Found [M+H] + = 457.2235.

[0728] FTIR (neat), cm -1 : 3247, 2956, 2930, 2845, 2794, 2768, 1728, 1606, 1540, 1524, 1479, 1445, 1378, 1292, 1226, 1190, 1161, 1138, 1120, 1102, 1072, 1000, 917, 871, 845, 827, 813, 798, 767, 695, 670, 536, 525.

[0729] Preparation Example 84: N-Phenyl-3-(pyridin-4-yl)furo[3,2-b]pyridin-6-amine

[0730]

[0731] (S)-(+)-1-[(R)-2-(Diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (Josiphos SL-J002-2; 2.8 mg, 0.05 mmol) and Pd(OAc)2 (1.2 mg, 0.05 mmol) were added to a degassed mixture of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21, 60 mg, 0.260 mmol), aniline (0.029 mL, 0.312 mmol), and sodium tert-butoxide (30 mg, 0.312 mmol) in 1,4-dioxane (5 mL) in a microwave vial. The resulting mixture was irradiated at 140 °C for 120 minutes. Then, the reaction mixture was diluted with water (15 mL) and extracted with EtOAc (3 × 5 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (DCM / MeOH, gradient 1:0 to 9:1). A brown solid product was obtained (51 mg, 68% yield).

[0732] 1 1H NMR (500 MHz, DMSO) δ 8.88 (s, 1H), 8.69 - 8.63 (m, 2H), 8.62 (s, 1H), 8.48 (d, J = 2.4 Hz, 1H), 8.25 - 8.13 (m, 2H), 7.76 (d, J = 2.3 Hz, 1H), 7.30 (dd, J = 8.5, 7.3 Hz, 2H), 7.22 - 7.15 (m, 2H), 6.92 (t, J = 7.3 Hz, 1H).

[0733] 13 13C NMR (126 MHz, DMSO) δ 149.95, 149.29, 146.79, 142.51, 138.45, 138.25, 138.07, 136.81, 129.36, 120.73, 120.59, 117.83, 117.05, 104.90.

[0734] HRMS (APCI): Calcd for C 18 H 13 N3O [M + H] + = 288.1131; Found [M + H] + = 288.1132.

[0735] FTIR (neat), cm -1 : 3245, 3102, 3028, 2925, 2851, 1593, 1488, 1436, 1415, 1381, 1331, 1282, 1233, 1181, 1099, 874, 837, 804, 751, 706, 671, 621, 607, 576, 560, 522, 499, 471, 445.

[0736] Preparation Example 85: tert-Butyl (3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzyl)carbamate

[0737]

[0738] Using 100 mg (0.430 mmol) of 3 - bromo - 6 - chlorofuro[3,2 - b]pyridine (Preparation Example 5) and 140 mg (0.559 mmol) of (3 - ((tert - butoxycarbonyl)amino)methyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 44:1) gave a pale yellow solid compound (154 mg, 100% yield).

[0739] 11H NMR (500 MHz, chloroform-d) δ 8.60 (d, J = 2.1 Hz, 1H), 8.10 (s, 1H), 7.95 - 7.90 (m, 2H), 7.82 (d, J = 2.1 Hz, 1H), 7.44 (td, J = 7.6, 0.8 Hz, 1H), 7.30 (d, J = 7.7 Hz, 1H), 4.94 (s, 1H), 4.40 (d, J = 5.8 Hz, 2H), 1.48 (s, 9H).

[0740] 13 13C NMR (126 MHz, CDCl3) δ 156.09, 148.53, 145.77, 145.30, 144.43, 139.83, 130.29, 129.35, 127.76, 127.33, 126.31, 121.81, 118.88, 79.70, 44.87, 28.58.

[0741] HRMS (APCI): Calcd for C 19 H 19 ClN2O3 [M + H] + = 359.1157; Found [M + H] + = 359.1161.

[0742] FTIR (neat), cm -1 : 3361, 3082, 2986, 2936, 1687, 1524, 1386, 1363, 1275, 1247, 1165, 1126, 1097, 1087, 1077, 1008, 909, 885, 789, 767, 697, 620, 607, 592.

[0743] Preparation Example 86: tert-Butyl 4-(4-(3-(3-(((tert-butoxycarbonyl)amino)methyl)phenyl)furo[3, 2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate

[0744]

[0745] Using 136 mg (0.379 mmol) of tert-butyl (3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzyl)carbamate (Preparation Example 85) and 191 mg (0.493 mmol) of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient of EtOAc from 1:0 to 1:1) gave a pale yellow solid compound (144 mg, 65% yield).

[0746] 11H NMR (500 MHz, chloroform-d) δ 8.79 (d, J = 1.9 Hz, 1H), 8.03 (s, 1H), 7.93 (dt, J = 7.7, 1.5 Hz, 1H), 7.90 (s, 1H), 7.84 (d, J = 1.9 Hz, 1H), 7.53 - 7.46 (m, 2H), 7.38 (t, J = 7.6 Hz, 1H), 7.22 (d, J = 7.7 Hz, 1H), 7.01 - 6.93 (m, 2H), 4.33 (d, J = 5.9 Hz, 2H), 3.57 - 3.51 (m, 4H), 3.15 (t, J = 5.2 Hz, 4H), 1.42 (s, 9H), 1.40 (s, 9H).

[0747] 13 13C NMR (126 MHz, CDCl3) δ 156.09, 154.87, 151.11, 149.41, 145.10, 145.08, 144.40, 139.69, 133.07, 130.97, 129.51, 129.32, 128.34, 127.08, 126.35, 121.73, 116.87, 116.09, 80.14, 49.09, 43.60, 28.59.

[0748] HRMS (APCI): Calcd for C 34 H 40 N4O5 [M + H] + = 585.3071; Found [M + H] + = 585.3074.

[0749] FTIR (neat), cm -1 3362, 2978, 2928, 2857, 1713, 1682, 1608, 1521, 1480, 1419, 1381, 1363, 1340, 1290, 1250, 1233, 1164, 1119, 1049, 1013, 999, 919, 879, 813, 791, 773, 696, 660, 531.

[0750] Preparation Example 87: (3-(6-(4-(Piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)phenyl)meth amine

[0751]

[0752] Using 130 mg (0.222 mmol) of tert-butyl 4-(4-(3-(3-(((tert-butoxycarbonyl)amino)methyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 86), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 4:1) gave the compound as a pale yellow solid (37 mg, 43% yield).

[0753] 1 H NMR (500 MHz, DMSO-d6) δ 8.94 (d, J = 1.9 Hz, 1H), 8.78 (s, 1H), 8.29 (d, J = 2.0 Hz, 1H), 8.17 (d, J = 1.8 Hz, 1H), 8.13 (dt, J = 7.7, 1.6 Hz, 1H), 7.74 - 7.66 (m, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.36 (dt, J = 7.7, 1.6 Hz, 1H), 7.10 - 6.99 (m, 2H), 3.83 (s, 2H), 3.18 - 3.07 (m, 4H), 2.92 - 2.81 (m, 4H).

[0754] 13 C NMR (126 MHz, DMSO) δ 151.35, 148.83, 146.43, 144.19, 143.90, 143.36, 132.25, 130.18, 128.44, 127.68, 126.74, 126.43, 125.35, 124.71, 120.27, 115.47, 115.42, 48.91, 45.51, 45.48.

[0755] HRMS (APCI): Calcd for C 24 H 24 N4O [M + H] + = 385.2023; Found [M + H] + = 385.2025.

[0756] FTIR (neat), cm -1 : 3032, 2954, 2922, 2820, 1660, 1604, 1523, 1478, 1450, 1378, 1237, 1182, 1120, 1095, 888, 818, 786, 751, 696, 666, 533.

[0757] Preparation Example 88: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)benzaldehyde

[0758]

[0759] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 84 mg (0.559 mmol) of 3-formylphenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 9:1) gave the compound as a white solid (84 mg, 76% yield).

[0760] 1 H NMR (500 MHz, chloroform-d) δ 10.12 (s, 1H), 8.65 (d, J = 2.0 Hz, 1H), 8.54 (t, J = 1.7 Hz, 1H), 8.38 (ddd, J = 7.7, 1.8, 1.2 Hz, 1H), 8.22 (s, 1H), 7.90 (dt, J = 7.6, 1.4 Hz, 1H), 7.87 (d, J = 2.0 Hz, 1H), 7.67 (t, J = 7.7 Hz, 1H).

[0761] 13 C NMR (126 MHz, CDCl3) δ 192.26, 148.56, 146.07, 145.56, 144.08, 137.09, 132.98, 131.18, 129.75, 129.14, 128.25, 128.08, 120.79, 119.03.

[0762] HRMS (APCI): Calcd for C 14 H8ClNO2 [M + H] + = 258.0316; Found [M + H] + = 258.0314.

[0763] FTIR (neat), cm -1 : 3138, 3106, 3068, 2858, 1686, 1602, 1565, 1484, 1461, 1386, 1359, 1270, 1239, 1176, 1126, 1097, 1077, 999, 915, 890, 877, 827, 791, 780, 719, 681, 651, 597, 522, 427, 411.

[0764] Preparation Example 89: 3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benz aldehyde

[0765]

[0766] Using 80 mg (0.310 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzaldehyde (Preparation Example 88) and 122 mg (0.404 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a white solid (109 mg, 88% yield).

[0767] 1 H NMR (500 MHz, DMSO-d6) δ 10.11 (s, 1H), 9.02 - 8.91 (m, 2H), 8.84 (t, J = 1.7 Hz, 1H), 8.57 (dt, J = 7.7, 1.5 Hz, 1H), 8.33 (d, J = 1.9 Hz, 1H), 7.92 (dt, J = 7.6, 1.4 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.73 - 7.68 (m, 2H), 7.07 (d, J = 8.9 Hz, 2H), 3.25 - 3.21 (m, 4H), 2.49 - 2.43 (m, 4H), 2.24 (s, 3H).

[0768] 13 C NMR (126 MHz, DMSO) δ 193.00, 150.76, 148.90, 147.36, 144.42, 143.01, 136.66, 135.66, 132.49, 132.20, 131.47, 129.56, 128.90, 127.73, 126.93, 126.75, 119.00, 115.68, 115.49, 113.69, 82.97, 54.44, 47.61, 45.72, 39.52, 24.63.

[0769] HRMS (APCI): Calcd for C 25 H 23 N3O2 [M + H] + = 398.1863; Found [M + H] + = 398.1863.

[0770] FTIR (neat), cm -12973,2940,2827,2797,1699,1604,1586,1524,1480,1450,1376,1362,1292,1238,1203,1175,1140,1118,1107,1008,921,887,821,799,790,688,671,655,538,521。

[0771] Preparation Example 90: (3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benz yl)methanol

[0772]

[0773] At 0 °C, NaBH4 (14 mg, 0.377 mmol) was added to a solution of 3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzaldehyde (Preparation Example 89; 100 mg, 0.252 mmol) in MeOH (10 mL), and the reaction mixture was stirred at 25 °C for 90 minutes. The reaction mixture was quenched by the addition of 1 M HCl (0.4 mL), the resulting solution was diluted with H2O (10 mL), and extracted with EtOAc (3 × 15 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1). A white solid product (93 mg, 93% yield) was obtained.

[0774] 1 1H NMR (500 MHz, DMSO-d6) δ 8.94 (s, 1H), 8.80 (s, 1H), 8.29 (s, 1H), 8.21 (s, 1H), 8.12 (d, J = 7.7 Hz, 1H), 7.70 (d, J = 8.2 Hz, 2H), 7.45 (t, J = 7.7 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.07 (d, J = 8.3 Hz, 2H), 5.23 (t, J = 5.7 Hz, 1H), 4.59 (d, J = 5.7 Hz, 2H), 3.26 - 3.16 (m, 4H), 2.48 (t, J = 5.1 Hz, 4H), 2.24 (s, 3H).

[0775] 1313C NMR (126 MHz, DMSO) δ 150.73, 148.83, 146.50, 144.20, 143.38, 142.92, 132.21, 130.15, 128.37, 127.71, 126.90, 125.75, 124.96, 124.66, 120.21, 115.51, 62.96, 54.45, 47.64, 45.73.

[0776] HRMS (APCI): Calcd for C 25 H 25 N3O2 [M + H] + = 400.2020; Found [M + H] + = 400.2016.

[0777] FTIR (neat), cm -1 : 2946, 2839, 2803, 1603, 1523, 1479, 1448, 1374, 1292, 1234, 1178, 1154, 1138, 1120, 1094, 1044, 1002, 919, 832, 799, 789, 753, 700, 672, 543, 528, 518.

[0778] Preparation Example 91: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-N,N-diphenylaniline

[0779]

[0780] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 162 mg (0.559 mmol) of (3-(diphenylamino)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 19:1) gave a pale yellow solid compound (121 mg, 71% yield).

[0781] 1 1H NMR (500 MHz, chloroform-d) δ 8.56 (d, J = 2.0 Hz, 1H), 7.97 (s, 1H), 7.86 - 7.73 (m, 2H), 7.62 (t, J = 2.0 Hz, 1H), 7.36 (t, J = 7.9 Hz, 1H), 7.29 - 7.20 (m, 6H), 7.17 - 7.12 (m, 4H), 7.11 - 7.06 (m, 2H), 7.05 - 6.98 (m, 3H).

[0782] 1313C NMR (126 MHz, CDCl3) δ 148.51, 148.44, 147.89, 147.88, 145.78, 145.30, 144.46, 130.99, 129.97, 129.56, 129.42, 129.39, 127.66, 124.51, 124.49, 123.85, 123.05, 123.00, 122.93, 122.60, 122.48, 121.95, 121.88, 121.44, 118.76。

[0783] HRMS (APCI): Calcd for C 25 H 17 ClN2O [M + H] + = 397.1102; found [M + H] + = 397.1100。

[0784] FTIR (neat), cm -1 : 3060, 3033, 1583, 1480, 1384, 1294, 1273, 1072, 932, 910, 874, 783, 750, 691, 658, 622, 597, 502。

[0785] Preparation Example 92: tert-Butyl 4-(4-(3-(3-(diphenylamino)phenyl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0786]

[0787] Using 100 mg (0.252 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-N,N-diphenylaniline (Preparation Example 91) and 127 mg (0.328 mmol) of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 h; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 4:1) gave the compound as a pale yellow solid (103 mg, 66% yield).

[0788] 11H NMR (500 MHz, chloroform-d) δ 8.92 (d, J = 1.8 Hz, 1H), 8.07 (s, 1H), 8.00 - 7.94 (m, 2H), 7.74 (t, J = 1.9 Hz, 1H), 7.69 - 7.62 (m, 2H), 7.48 (t, J = 7.9 Hz, 1H), 7.39 - 7.31 (m, 4H), 7.29 - 7.22 (m, 3H), 7.18 (ddd, J = 8.0, 2.3, 1.0 Hz, 1H), 7.16 - 7.08 (m, 4H), 3.72 (t, J = 5.2 Hz, 4H), 3.32 (t, J = 5.2 Hz, 4H), 1.60 (s, 9H).

[0789] 13 13C NMR (126 MHz, CDCl3) δ 154.87, 149.33, 148.42, 147.96, 145.16, 145.09, 144.43, 132.95, 131.68, 129.97, 129.38, 128.35, 124.41, 123.83, 122.92, 122.66, 122.23, 121.81, 116.92, 116.03, 80.16, 49.17, 43.52, 28.60, 27.08.

[0790] HRMS (APCI): Calcd for C 40 H 38 N4O3 [M + H] + = 623.3017; Found [M + H] + = 623.3020.

[0791] FTIR (neat), cm -1 2975, 2919, 2851, 2363, 2342, 1695, 1607, 1586, 1524, 1492, 1423, 1267, 1233, 1167, 754, 697.

[0792] Preparation Example 93: N,N-Diphenyl-3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)aniline

[0793]

[0794] Using 75 mg (0.120 mmol) of tert-butyl 4-(4-(3-(3-(diphenylamino)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 92), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a white solid (54 mg, 86% yield).

[0795] 1 H NMR (500 MHz, DMSO-d6) δ 8.84 (d, J = 1.9 Hz, 1H), 8.74 (s, 1H), 8.26 (d, J = 1.9 Hz, 1H), 8.02 (t, J = 2.0 Hz, 1H), 7.91 (dt, J = 7.7, 1.3 Hz, 1H), 7.69 - 7.64 (m, 2H), 7.43 (t, J = 7.9 Hz, 1H), 7.37 - 7.27 (m, 4H), 7.10 - 7.00 (m, 8H), 6.98 (ddd, J = 8.1, 2.3, 1.0 Hz, 1H), 3.15 (dd, J = 6.2, 4.0 Hz, 4H), 2.99 - 2.80 (m, 4H).

[0796] 13 C NMR (126 MHz, DMSO) δ 171.97, 151.17, 148.78, 147.54, 147.24, 146.77, 144.18, 143.13, 132.24, 131.76, 129.88, 129.45, 127.67, 126.79, 123.71, 123.41, 122.72, 122.56, 121.76, 119.80, 115.46, 48.52, 45.17.

[0797] HRMS (APCI): Calcd for C 35 H 30 N4O [M + H] + = 523.2492; Found [M + H] + = 523.2495.

[0798] FTIR (neat), cm -1 : 3348, 3036, 2950, 2919, 2847, 1585, 1489, 1453, 1380, 1281, 1261, 1237, 1106, 931, 827, 789, 750, 693, 668, 542, 503.

[0799] Preparation Example 94: 3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benz yl acetate

[0800]

[0801] Ac2O (14 μL, 0.150 mmol) and DMAP (38 mg, 0.313 mmol) were added to a solution of 3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)phenyl)methanol (Preparation Example 90; 50 mg, 0.125 mmol) in DMF (5 mL). The reaction mixture was stirred at 60 °C for 60 minutes. After cooling to ambient temperature, the reaction mixture was diluted with H2O (10 mL) and extracted with EtOAc (3 × 15 mL). The combined organic extracts were washed with brine (3 × 10 mL), dried over MgSO4, and filtered. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (DCM / MeOH, gradient 1:0 to 4:1). A pale yellow solid product (42 mg, 76% yield) was obtained.

[0802] 1 H NMR (500 MHz, DMSO-d6) δ 8.95 (d, J = 1.9 Hz, 1H), 8.84 (s, 1H), 8.30 (d, J = 1.9 Hz, 1H), 8.25 (d, J = 1.8 Hz, 1H), 8.23 (dt, J = 7.8, 1.4 Hz, 1H), 7.72 - 7.66 (m, 2H), 7.51 (t, J = 7.7 Hz, 1H), 7.37 (dt, J = 7.7, 1.5 Hz, 1H), 7.11 - 7.01 (m, 2H), 5.16 (s, 2H), 3.26 - 3.21 (m, 4H), 2.25 (s, 3H), 2.11 (s, 3H).

[0803] 13 C NMR (126 MHz, DMSO) δ 170.20, 150.71, 148.85, 146.77, 144.28, 143.24, 136.62, 132.29, 130.63, 128.80, 127.72, 127.16, 126.86, 126.16, 126.01, 119.74, 115.57, 115.51, 65.41, 54.41, 47.59, 45.66, 20.70.

[0804] HRMS (APCI): Calcd for C 27 H 27 N3O3 [M + H] + = 442.2125; Found [M + H] + = 442.2121.

[0805] FTIR (neat), cm -1 : 2938, 2845, 2412, 1733, 1607, 1523, 1480, 1457, 1376, 1357, 1243, 1185, 1168, 1107, 1055, 1029, 986, 914, 889, 839, 798, 701, 550, 531.

[0806] Preparation Example 95: (E)-3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzaldoxime

[0807]

[0808] At 0 °C, pyridine (40 μL, 0.503 mmol) and hydroxylamine hydrochloride (26 mg, 0.377 mmol) were added to a solution of 3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzaldehyde (Preparation Example 89; 100 mg, 0.252 mmol) in EtOH (5 mL), and the reaction mixture was stirred at 25 °C for 18 h. The solvent was evaporated in vacuo, the residue was diluted with EtOAc (10 mL), and extracted with H2O (3 × 10 mL). The organic layer was dried over MgSO4 and filtered. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1). A white solid product was obtained (83 mg, 80% yield).

[0809] 1 1H NMR (500 MHz, DMSO-d6) δ 11.32 (s, 1H), 10.36 (s, 1H), 8.97 (d, J = 1.9 Hz, 1H), 8.87 (s, 1H), 8.56 (t, J = 1.8 Hz, 1H), 8.35 (d, J = 1.9 Hz, 1H), 8.29 - 8.15 (m, 2H), 7.82 - 7.71 (m, 2H), 7.62 - 7.49 (m, 2H), 7.23 - 7.07 (m, 2H), 3.29 (s, 4H), 2.82 (s, 3H).

[0810] 13 13C NMR (126 MHz, DMSO) δ 149.29, 148.81, 147.92, 147.04, 144.37, 143.41, 133.51, 132.05, 130.83, 129.05, 128.11, 127.93, 127.30, 125.95, 124.17, 119.67, 116.17, 115.82, 51.98, 45.18, 42.07.

[0811] FTIR (neat), cm -1 : 3401, 3186, 2966, 2688, 2593, 1605, 1523, 1476, 1457, 1378, 1245, 1185, 1107, 1017, 987, 971, 949, 920, 826, 801, 696, 682, 639, 545, 521。

[0812] Preparation Example 96: N 1 ,N 1 ,N 2 -trimethyl-N 2 -(4-nitrophenyl)ethane-1,2-diamine

[0813]

[0814] N,N,N′-Trimethylethylenediamine (0.561 mL, 4.337 mmol) was added to a mixture of 4-fluoronitrobenzene (612 mg, 4.337 mmol) and K2CO3 (1.199 g, 8.675 mmol) in DMSO (20 mL). The reaction mixture was stirred at 70 °C for 18 hours. The reaction mixture was cooled to 25 °C and treated with brine (25 mL) and EtOAc (30 mL). The organic layer was extracted with brine (5 × 25 mL), dried over MgSO4, filtered, and evaporated in vacuo. A yellow oil product (901 mg, 93% yield) was obtained.

[0815] 1 1H NMR (500 MHz, chloroform-d) δ 8.11 (d, J = 9.4 Hz, 2H), 6.62 (d, J = 9.4 Hz, 2H), 3.57 - 3.53 (m, 2H), 3.10 (s, 3H), 2.61 - 2.43 (m, 2H), 2.30 (s, 6H).

[0816] 13 13C NMR (126 MHz, CDCl3) δ 153.54, 137.17, 126.40, 110.33, 56.13, 51.18, 46.01, 39.15.

[0817] HRMS (APCI): Calcd for C 11 H 17 N3O2 [M + H] + = 224.1394; Found [M + H] + = 224.1393.

[0818] FTIR (neat), cm -1 : 2973, 2943, 2821, 2771, 1594, 1519, 1485, 1301, 1255, 1200, 1110, 825, 753.

[0819] Preparation Example 97:N 1 -(2-(Dimethylamino)ethyl)-N 1 -methylbenzene-1,4-diamine

[0820]

[0821] To a degassed mixture of ethanol (5 mL) and Pd / C (10.0 mg) was added N 1 ,N 1 ,N 2 -trimethyl-N 2 -(4-nitrophenyl)ethane-1,2-diamine (Preparation Example 96, 900 mg, 4.031 mmol), and the resulting mixture was stirred under a hydrogen atmosphere at 25 °C for 18 h. Then, the reaction mixture was filtered through a syringe filter ( Xtra PTFE-20 / 25 0.25 μm), and the solvent was evaporated in vacuo. A pale yellow oil product (771 mg, 99% yield) was obtained without further purification.

[0822] 1 1H NMR (500 MHz, chloroform-d) δ 6.65 (s, 4H), 3.38 - 3.23 (m, 2H), 2.84 (s, 3H), 2.59 - 2.40 (m, 2H), 2.27 (s, 6H).

[0823] 13 13C NMR (126 MHz, CDCl3) δ 143.66, 137.72, 116.93, 115.50, 56.37, 52.76, 46.04, 39.72.

[0824] FTIR (neat), cm -1 : 2946, 2823, 2779, 1673, 1596, 1556, 1515, 1465, 1372, 1303, 1251, 1218, 1156, 1115, 1041, 960, 820.

[0825] Preparation Example 98: N 1 -(2-(dimethylamino)ethyl)-N 1 -methyl-N 4 -(3-(pyridin-4-yl)furo [3,2-b]pyridin-6-yl)benzene-1,4-diamine

[0826]

[0827] (S)-(+)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (Josiphos SL-J002-2; 2.4 mg, 0.04 mmol) and Pd(OAc)2 (1.0 mg, 0.04 mmol) were added to 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21, 50 mg, 0.217 mmol) in a microwave vial, N 1-(2-(Dimethylamino)ethyl)-N 1 -Methylbenzene-1,4-diamine (Preparation Example 97, 50 mg, 0.260 mmol) and sodium tert-butoxide (25 mg, 0.260 mmol) were in a degassed mixture in 1,4-dioxane (5 mL). The resulting mixture was irradiated at 140 °C for 120 minutes. Then, the reaction mixture was diluted with water (15 mL) and extracted with EtOAc (3 × 5 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was evaporated under vacuum. The residue was purified by flash chromatography (2% TEA in DCM / MeOH with a gradient of 1:0 to 19:1). A pale yellow oil product (19 mg, 23% yield) was obtained.

[0828] 1 1H NMR (500 MHz, chloroform-d) δ 8.71 - 8.61 (m, 2H), 8.30 (d, J = 2.4 Hz, 1H), 8.05 (s, 1H), 8.02 - 7.95 (m, 2H), 7.10 (d, J = 8.9 Hz, 2H), 6.74 (d, J = 8.9 Hz, 2H), 5.65 (s, 1H), 3.51 - 3.41 (m, 2H), 2.97 (s, 3H), 2.59 - 2.48 (m, 2H), 2.32 (s, 6H).

[0829] 13 13C NMR (126 MHz, CDCl3) δ 150.44, 150.42, 146.85, 144.12, 141.43, 138.95, 137.02, 136.94, 130.33, 124.36, 121.30, 119.47, 113.53, 102.94, 56.21, 51.68, 46.04, 39.02.

[0830] FTIR (neat), cm -1 : 3260, 2957, 2937, 2853, 2810, 2785, 2763, 1601, 1575, 1513, 1497, 1419, 1343, 1298, 1284, 1239, 1181, 1158, 1101, 1044, 995, 951, 854, 834, 806, 794, 755, 689, 630, 610, 519, 488.

[0831] Preparation Example 99: 3,6-Di(pyridin-4-yl)furo[3,2-b]pyridine

[0832]

[0833] Using 60 mg (0.260 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 42 mg (0.338 mmol) of 4-pyridylboronic acid, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a pale yellow solid (41 mg, 58% yield).

[0834] 1 H NMR (500 MHz, chloroform-d) δ 8.97 (d, J = 1.8 Hz, 1H), 8.75 (dd, J = 11.7, 6.2 Hz, 3H), 8.36 (s, 1H), 8.15 - 7.91 (m, 3H), 7.69 - 7.51 (m, 2H).

[0835] 13 C NMR (126 MHz, CDCl3) δ 150.81, 150.54, 149.22, 147.75, 145.99, 145.46, 145.33, 137.97, 130.81, 121.95, 121.40, 119.77, 117.16.

[0836] HRMS (APCI): Calcd for C 18 H 12 N2O [M + H] + = 273.1022; Found [M + H] + = 273.1020.

[0837] FTIR (neat), cm -1 3088, 3026, 1600, 1385, 1224, 1096, 995, 982, 816, 683, 542, 523.

[0838] Preparation Example 100: 6-Chloro-3-phenylfuro[3,2-b]pyridine

[0839]

[0840] Using 85 mg (0.365 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 53 mg (0.439 mmol) of phenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, 0% to 10% EtOAc gradient) gave the compound as a white solid (60 mg, 71% yield).

[0841] 11H NMR (500 MHz, chloroform-d) δ 8.62 (d, J = 2.0 Hz, 1H), 8.10 (s, 1H), 8.07 - 7.98 (m, 2H), 7.82 (d, J = 2.1 Hz, 1H), 7.48 (dd, J = 8.4, 7.0 Hz, 2H), 7.44 - 7.35 (m, 1H).

[0842] 13 13C NMR (126 MHz, CDCl3) δ 148.54, 145.60, 145.31, 144.53, 129.97, 129.04, 128.17, 127.71, 127.26, 122.03, 118.83.

[0843] HRMS (APCI): Calcd for C 13 H8ClNO [M + H] + = 230.0367; Found [M + H] + = 230.0370.

[0844] FTIR (neat), cm -1 : 3063, 1605, 1487, 1443, 1383, 1267, 1222, 1132, 1089, 1070, 965, 906, 880, 817, 777, 751, 691, 654, 617, 594, 520, 503.

[0845] Preparation Example 101: N-(4-(4-Methylpiperazin-1-yl)phenyl)-3-phenylfuro[3,2-b]pyridin-6- Amine

[0846]

[0847] (S)-(+)-1-[(R)-2-(Diphenylphosphino)ferrocenyl]ethyldi-tert-butylphosphine (Josiphos SL-J002-2; 2.4 mg, 0.04 mmol) and Pd(OAc)2 (1.0 mg, 0.04 mmol) were added to a degassed mixture of 6-chloro-3-phenylfuro[3,2-b]pyridine (Preparation Example 100, 50 mg, 0.218 mmol), 4-(4-methylpiperazinyl)aniline (50 mg, 0.231 mmol), and sodium tert-butoxide (25 mg, 0.261 mmol) in 1,4-dioxane (5 mL) in a microwave vial. The resulting mixture was irradiated at 140 °C for 120 minutes. Then, the reaction mixture was diluted with water (15 mL) and extracted with EtOAc (3 × 5 mL). The combined organic extracts were dried over MgSO4, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (2% TEA in DCM / MeOH, gradient from 1:0 to 9:1). A pale yellow solid product was obtained (31 mg, 37% yield).

[0848] 1 1H NMR (500 MHz, chloroform-d) δ 8.34 (d, J = 2.3 Hz, 1H), 8.07 - 8.00 (m, 2H), 7.94 (s, 1H), 7.46 (dd, J = 8.4, 7.0 Hz, 2H), 7.40 - 7.30 (m, 2H), 7.13 - 7.06 (m, 2H), 6.99 - 6.90 (m, 2H), 5.67 (s, 1H), 3.20 (t, J = 5.0 Hz, 4H), 2.62 (t, J = 4.9 Hz, 4H), 2.38 (s, 3H).

[0849] 13 13C NMR (126 MHz, CDCl3) δ 149.94, 147.75, 142.95, 139.50, 138.58, 137.44, 134.43, 130.99, 128.90, 127.62, 127.13, 121.94, 121.76, 117.70, 104.34, 67.22, 55.29, 50.85, 49.87, 46.25.

[0850] HRMS (APCI): Calcd for C 24 H 24 N4O [M + H] + = 385.2023; Found [M + H] + = 385.2024.

[0851] FTIR (neat), cm -1: 391,3056,2972,2941,2929,2847,2796,2756,1607,1577,1564,1514,1501,1464,1447,1382,1339,1289,1237,1189,1165,1145,1107,1081,1000,916,857,806,768,746,692,634,530,503。

[0852] Preparation Example 102: 6-Chloro-3-(3-phenoxyphenyl)furo[3,2-b]pyridine

[0853]

[0854] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 120 mg (0.559 mmol) of 3-phenoxybenzeneboronic acid, the compound was prepared by General Procedure A; the reaction time was 3 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 19:1) gave the compound as a colorless oil (117 mg, 84% yield).

[0855] 1 H NMR (500 MHz, CDCl3) δ 8.60 (d, J = 2.0 Hz, 1H), 8.09 (s, 1H), 7.84 - 7.80 (m, 2H), 7.72 - 7.69 (m, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.38 - 7.33 (m, 2H), 7.12 (t, J = 7.4 Hz, 1H), 7.09 - 7.06 (m, 2H), 7.00 (dd, J = 8.1, 2.3 Hz, 1H).

[0856] 13 C NMR (126 MHz, CDCl3) δ 157.81, 157.32, 148.54, 145.88, 145.43, 144.36, 131.75, 130.38, 129.94, 127.83, 123.50, 122.25, 121.52, 119.10, 118.87, 118.48, 117.81.

[0857] HRMS (APCI): Calcd for C 19 H 12 ClNO2 [M + H] + = 322.0629; Found [M + H] + = 322.0630.

[0858] Preparation Example 103: tert-Butyl 4-(4-(3-(3-phenoxyphenyl)furo[3,2-b]pyridin-6-yl)phenyl )piperazine-1-carboxylate

[0859]

[0860] Using 67 mg (0.208 mmol) of 6-chloro-3-(3-phenoxyphenyl)furo[3,2-b]pyridine (Preparation Example 102) and 105 mg (0.271 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 4:1) gave the compound as an off-white solid (104 mg, 91% yield).

[0861] 1 H NMR (500 MHz, CDCl3) δ 8.79 (d, J = 1.8 Hz, 1H), 8.01 (s, 1H), 7.83 (dd, J = 4.6, 2.7 Hz, 2H), 7.70 - 7.66 (m, 1H), 7.50 (d, J = 8.7 Hz, 2H), 7.38 (t, J = 7.9 Hz, 1H), 7.28 (t, J = 8.0 Hz, 2H), 7.06 - 6.95 (m, 5H), 6.92 (dd, J = 8.2, 1.7 Hz, 1H), 3.58 - 3.52 (m, 4H), 3.19 - 3.12 (m, 4H), 1.42 (s, 9H).

[0862] 13 C NMR (126 MHz, CDCl3) δ 157.70, 157.46, 154.87, 149.43, 145.25, 145.17, 144.31, 133.10, 132.42, 130.33, 129.90, 128.38, 123.37, 122.39, 121.43, 119.02, 118.28, 117.87, 116.97, 116.12, 80.18, 49.21, 43.56, 28.60.

[0863] HRMS (APCI): Calcd for C 34 H 33 N3O4 [M + H] + = 548.2544; Found [M + H] + = 548.2548.

[0864] Preparation Example 104: 3-(3-Phenoxyphenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[0865]

[0866] TFA (0.1 mL, 1.31 mmol) was added to a solution of tert-butyl 4-(4-(3-(3-phenoxyphenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 103; 19 mg, 0.035 mmol) in DCM (1.0 mL), and the resulting mixture was stirred at 25 °C; the progress of the reaction was monitored by TLC. After consumption of the starting material (1 h), the mixture was basified with 2 M NaOH (2.0 mL) and extracted with EtOAc (3 x 20 mL). The combined organic phases were dried over MgSO4 and evaporated in vacuo. Flash chromatography (DCM / MeOH, gradient 9:1 to 7:3) gave the compound as an off-white solid (9 mg, 54% yield).

[0867] 1 H NMR (500 MHz, DMSO) δ 8.91 (d, J = 1.9 Hz, 1H), 8.87 (s, 1H), 8.30 (d, J = 1.9 Hz, 1H), 8.12 - 8.08 (m, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.45 - 7.38 (m, 2H), 7.15 (t, J = 7.4 Hz, 1H), 7.09 - 7.03 (m, 4H), 6.98 (dd, J = 8.1, 1.9 Hz, 1H), 3.17 - 3.11 (m, 4H), 2.89 - 2.84 (m, 4H).

[0868] 13 C NMR (126 MHz, DMSO) δ 156.87, 156.59, 151.33, 148.88, 147.10, 144.28, 143.08, 132.46, 132.36, 130.27, 130.01, 127.68, 126.67, 123.24, 121.79, 119.34, 118.18, 117.83, 117.31, 115.56, 115.42, 48.80, 45.39.

[0869] HRMS (APCI): Calcd for C 29 H 25 N3O2 [M + H] + = 448.2020; Found [M + H] + = 448.2017.

[0870] Preparation Example 105: 6-Chloro-3-(3-(pyridin-4-yl)phenyl)furo[3,2-b]pyridine

[0871]

[0872] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 111 mg (0.559 mmol) of 3-(pyridin-4-yl)phenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 3 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) gave the compound as a white solid (100 mg, 76% yield).

[0873] 1 H NMR (500 MHz, CDCl3) δ 8.70 (dd, J = 4.5, 1.6 Hz, 1H), 8.65 (d, J = 2.0 Hz, 1H), 8.37 (t, J = 1.6 Hz, 1H), 8.19 (s, 1H), 8.08 (dt, J = 7.5, 1.4 Hz, 1H), 7.86 (d, J = 2.0 Hz, 1H), 7.65 (dt, J = 7.7, 1.5 Hz, 1H), 7.63 - 7.57 (m, 2H).

[0874] 13 C NMR (126 MHz, CDCl3) δ 150.53, 148.61, 148.28, 145.85, 145.56, 144.38, 139.09, 131.03, 129.84, 127.98, 127.77, 126.76, 126.02, 121.92, 121.59, 118.98.

[0875] HRMS (APCI): Calcd for C 18 H 11 ClN2O [M + H] + = 307.0633; Found [M + H] + = 307.0635.

[0876] Preparation Example 106: tert-Butyl 4-(4-(3-(3-(pyridin-4-yl)phenyl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0877]

[0878] Using 48 mg (0.156 mmol) of 6-chloro-3-(3-(pyridin-4-yl)phenyl)furo[3,2-b]pyridine (Preparation Example 105) and 79 mg (0.203 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 3:2 to 1:4) gave the compound as an off-white solid (80 mg, 96% yield).

[0879] 1 1H NMR (500 MHz, CDCl3) δ 8.91 (d, J = 1.9 Hz, 1H), 8.71 (d, J = 5.9 Hz, 2H), 8.47 (s, 1H), 8.20 (s, 1H), 8.15 (dt, J = 7.2, 1.6 Hz, 1H), 7.95 (d, J = 1.9 Hz, 1H), 7.71 - 7.57 (m, 6H), 7.05 (d, J = 8.8 Hz, 2H), 3.65 - 3.59 (m, 4H), 3.27 - 3.21 (m, 4H), 1.50 (s, 9H).

[0880] 13 13C NMR (126 MHz, CDCl3) δ 154.89, 151.18, 150.40, 149.50, 148.51, 145.31, 145.17, 144.33, 138.96, 133.27, 131.72, 129.79, 129.42, 128.37, 127.85, 126.46, 126.02, 121.99, 121.49, 116.87, 116.16, 80.17, 49.08, 43.78, 28.60.

[0881] HRMS (APCI): Calculated for C 33 H 32 N4O3 [M + H] + = 533.2547; Found [M + H] + = 533.2550.

[0882] Preparation Example 107: 6-(4-(Piperazin-1-yl)phenyl)-3-(3-(pyridin-4-yl)phenyl)furo[3,2- b]pyridine

[0883]

[0884] TFA (0.1 mL, 1.31 mmol) was added to a solution of tert-butyl 4-(4-(3-(3-(pyridin-4-yl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 106; 15 mg, 0.029 mmol) in DCM (1.0 mL), and the resulting mixture was stirred at 25 °C; the progress of the reaction was monitored by TLC. After consumption of the starting material (1 h), the mixture was basified with 2 M NaOH (2.0 mL) and extracted with EtOAc (3 x 20 mL). The combined organic phases were dried over MgSO4 and evaporated in vacuo. The yellow solid compound was isolated (8 mg, 64% yield) without further purification.

[0885] 11H NMR (500 MHz, DMSO) δ 8.94 - 8.90 (m, 2H), 8.67 - 8.63 (m, 2H), 8.59 (t, J = 1.6 Hz, 1H), 8.39 - 8.35 (m, 1H), 8.29 - 8.26 (m, 1H), 7.77 - 7.73 (m, 3H), 7.69 - 7.64 (m, 2H), 7.62 (t, J = 7.8 Hz, 1H), 7.06 - 6.89 (m, 1H), 3.14 - 3.06 (m, 4H), 2.87 - 2.79 (m, 4H).

[0886] 13 13C NMR (126 MHz, DMSO) δ 151.40, 150.26, 148.92, 147.16, 146.94, 144.36, 143.22, 137.70, 132.41, 131.44, 129.60, 127.70, 127.30, 126.65, 125.96, 124.78, 121.32, 119.66, 115.59, 115.41, 48.94, 45.52.

[0887] HRMS (APCI): Calcd for C 28 H 24 N4O [M + H] + = 433.2023; Found [M + H] + = 433.2021.

[0888] Preparation Example 108: tert-Butyl (3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)(methyl)carbam ate

[0889]

[0890] Using 200 mg (0.860 mmol) of 3 - bromo - 6 - chlorofuro[3,2 - b]pyridine (Preparation Example 5) and 282 mg (1.12 mmol) of (3 - ((tert - butoxycarbonyl)(methyl)amino)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 44:1) gave the compound as a white solid (283 mg, 92% yield).

[0891] 11H NMR (500 MHz, CDCl3) δ 8.61 (d, J = 2.0 Hz, 1H), 8.12 (s, 1H), 7.99 (t, J = 1.9 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.82 - 7.80 (m, 1H), 7.43 (t, J = 7.9 Hz, 1H), 7.26 - 7.23 (m, 1H), 3.33 (s, 3H), 1.48 (s, 9H).

[0892] 13 13C NMR (126 MHz, CDCl3) δ 154.91, 148.56, 145.78, 145.32, 144.59, 144.39, 130.42, 129.18, 127.81, 125.18, 124.48, 124.07, 121.61, 118.90, 80.60, 37.50, 28.51.

[0893] HRMS (APCI): Calcd for C 19 H 19 ClN2O3 [M + H] + = 359.1157; Found [M + H] + = 359.1161.

[0894] Preparation Example 109: tert-Butyl methyl 3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]py ridin-3-yl)phenyl)carbamate

[0895]

[0896] Using 226 mg (0.630 mmol) of tert-butyl (3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)(methyl)carbamate (Preparation Example 108) and 247 mg (0.817 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2.5 h; flash chromatography (DCM / MeOH, gradient 1:0 to 19:1) gave the compound as an off-white solid (228 mg, 73% yield).

[0897] 11H NMR (500 MHz, CDCl3) δ 8.87 (d, J = 1.9 Hz, 1H), 8.11 (s, 1H), 8.03 (t, J = 1.8 Hz, 1H), 7.92 (d, J = 1.9 Hz, 1H), 7.91 - 7.87 (m, 1H), 7.59 - 7.55 (m, 2H), 7.44 (t, J = 7.9 Hz, 1H), 7.24 (br d, J = 8.1 Hz, 1H), 7.07 - 7.03 (m, 2H), 3.34 (s, 3H), 3.33 - 3.28 (m, 4H), 2.65 - 2.58 (m, 4H), 2.38 (s, 3H), 1.48 (s, 9H).

[0898] 13 13C NMR (126 MHz, CDCl3) δ 154.97, 151.21, 149.46, 145.14, 145.01, 144.53, 144.29, 133.25, 131.19, 129.12, 128.92, 128.30, 124.97, 124.41, 124.18, 121.54, 116.35, 116.02, 80.52, 55.19, 48.83, 46.32, 37.55, 28.53.

[0899] HRMS (APCI): Calcd for C 30 H 34 N4O3 [M + H] + = 499.2704; Found [M + H] + = 499.2706.

[0900] Preparation Example 110: N-Methyl-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin- 3-yl)aniline

[0901]

[0902] HCl (35% aqueous solution, 2.0 mL) was added to a suspension of 140 mg (0.281 mmol) of tert-butyl methyl (3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)phenyl)carbamate (Preparation Example 109) in MeOH (2.0 mL). The reaction mixture was stirred at 50 °C for 1 hour and then evaporated in vacuo. A mixture of DCM / MeOH 95:5 (5.0 mL) and NH3 (7 M solution in MeOH, 1.0 mL, 7.0 mmol) was added to the mixture, and the mixture was stirred for 1 hour and then evaporated in vacuo. Flash chromatography (DCM / MeOH, 0% to 6% MeOH gradient) gave the compound as an off-white solid (104 mg, 74% yield).

[0903] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.9 Hz, 1H), 8.11 (s, 1H), 7.93 (d, J = 1.9 Hz, 1H), 7.62 - 7.57 (m, 2H), 7.46 - 7.42 (m, 1H), 7.39 - 7.36 (m, 1H), 7.32 (t, J = 7.8 Hz, 1H), 7.10 - 7.05 (m, 2H), 6.65 (dd, J = 7.9, 1.4 Hz, 1H), 3.87 (br s, 1H), 3.35 (br s, 4H), 2.94 (s, 3H), 2.66 (br s, 4H), 2.43 (br s, 3H).

[0904] 13 13C NMR (126 MHz, DMSO) δ 150.09, 149.60, 148.75, 146.40, 144.10, 143.77, 131.83, 130.75, 129.03, 127.95, 127.84, 120.89, 116.02, 115.58, 114.24, 111.24, 109.79, 52.67, 45.86, 43.10, 29.82.

[0905] HRMS (APCI): Calculated for C 25 H 26 N4O [M + H] + = 399.2179; Found [M + H] + = 399.2183.

[0906] Preparation Example 111: 6-Chloro-3-(3-(trifluoromethoxy)phenyl)furo[3,2-b]pyridine

[0907]

[0908] Using 60 mg (0.258 mmol) of 3 - bromo - 6 - chlorofuro[3,2 - b]pyridine (Preparation Example 5) and 70 mg (0.340 mmol) of (3 - (trifluoromethoxy)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 3 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 93:7) gave the compound as a white solid (74 mg, 91% yield).

[0909] 11H NMR (500 MHz, CDCl3) δ 8.64 (d, J = 2.0 Hz, 1H), 8.15 (s, 1H), 8.01 - 7.98 (m, 1H), 7.96 (br s, 1H), 7.85 (d, J = 2.0 Hz, 1H), 7.50 (t, J = 8.0 Hz, 1H), 7.25 - 7.21 (m, 1H).

[0910] 13 13C NMR (126 MHz, CDCl3) δ 149.89, 148.59, 146.04, 145.62, 144.05, 132.07, 130.39, 128.09, 125.47, 120.78, 120.72 (q, J = 257.4 Hz), 120.36, 119.79, 119.02.

[0911] HRMS (APCI): Calcd for C 14 H7ClF3NO2 [M + H] + = 314.0190; Found [M + H] + = 314.0189.

[0912] Preparation Example 112: tert-Butyl 4-(4-(3-(3-(trifluoromethoxy)phenyl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[0913]

[0914] Using 55 mg (0.175 mmol) of 6-chloro-3-(3-(trifluoromethoxy)phenyl)furo[3,2-b]pyridine (Preparation Example 111) and 88 mg (0.228 mmol) of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid pinacol ester, the compound was prepared by the general procedure B; the reaction time was 1 hour; flash chromatography (cyclohexane / EtOAc, gradient from 9:1 to 7:3) gave the compound as a white solid (81 mg, 86% yield).

[0915] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.9 Hz, 1H), 8.15 (s, 1H), 8.09 - 8.04 (m, 1H), 8.01 (s, 1H), 7.93 (d, J = 1.9 Hz, 1H), 7.62 - 7.56 (m, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.24 - 7.20 (m, 1H), 7.06 (br d, J = 8.6 Hz, 2H), 3.67 - 3.58 (m, 4H), 3.29 - 3.20 (m, 4H), 1.50 (s, 9H).

[0916] 13 13C NMR (126 MHz, CDCl3) δ 154.86, 149.88, 149.86, 149.48, 145.39, 145.32, 144.02, 133.33, 132.75, 130.31, 128.40, 125.49, 121.76, 120.70, 120.04, 119.75, 119.72, 116.99, 116.21, 80.20, 49.21, 43.65, 28.59.

[0917] Preparation Example 113: 6-(4-(Piperazin-1-yl)phenyl)-3-(3-(trifluoromethoxy)phenyl]furo[3,2- b]pyridine

[0918]

[0919] Using 61 mg (0.113 mmol) of tert-butyl 4-(4-(3-(3-(trifluoromethoxy)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 112), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 4:1 to 1:1) gave the compound as a pale yellow solid (44 mg, 89% yield).

[0920] 1 1H NMR (500 MHz, CDCl3) δ 8.90 (d, J = 1.9 Hz, 1H), 8.14 (s, 1H), 8.09 - 8.04 (m, 1H), 8.01 (br s, 1H), 7.93 (d, J = 1.9 Hz, 1H), 7.61 - 7.55 (m, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.24 - 7.20 (m, 1H), 7.07 - 7.03 (m, 2H), 3.30 - 3.21 (m, 4H), 3.14 - 3.03 (m, 4H).

[0921] 13 13C NMR (126 MHz, CDCl3) δ 151.70, 149.87, 149.53, 145.36, 145.29, 143.91, 133.51, 132.81, 130.31, 128.85, 128.30, 125.51, 121.77, 120.71, 120.02, 119.76, 116.42, 116.13, 49.94, 46.08.

[0922] HRMS (APCI): Calcd for C 24 H 20 F3N3O2 [M + H] += 440.1580; Measured value [M+H] + = 440.1583.

[0923] Preparation Example 114: 6-Chloro-3-(3-(2,2,2-trifluoroethoxy)phenyl)furo[3,2-b]pyridine

[0924]

[0925] Using 75 mg (0.32 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 92 mg (0.42 mmol) of (3-(2,2,2-trifluoroethoxy)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 1 hour; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 9:1) gave the compound as a pale yellow solid (103 mg, 98% yield).

[0926] 1 H NMR (500 MHz, CDCl3) δ 8.63 (d, J = 2.0 Hz, 1H), 8.12 (s, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.77 - 7.75 (m, 1H), 7.67 (d, J = 7.7 Hz, 1H), 7.42 (t, J = 8.0 Hz, 1H), 6.96 (dd, J = 8.3, 2.5 Hz, 1H), 4.45 (q, J = 8.1 Hz, 2H).

[0927] 13 C NMR (126 MHz, CDCl3) δ 157.96, 148.57, 145.92, 145.46, 144.28, 131.76, 130.32, 127.91, 123.55 (q, J = 278.8 Hz), 121.36, 121.25, 118.94, 114.60, 113.99, 66.11 (q, J = 35.9 Hz).

[0928] Preparation Example 115: tert-Butyl 4-(4-(3-(3-(2,2,2-trifluoroethoxy)phenyl)furo[3,2-b]py ridin-6-yl)phenyl)piperazine-1-carboxylate

[0929]

[0930] Using 85 mg (0.259 mmol) of 6-chloro-3-(3-(2,2,2-trifluoroethoxy)phenyl)furo[3,2-b]pyridine (Preparation Example 114) and 131 mg (0.337 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / Et2O, gradient from 7:3 to 2:3) gave the compound as a white solid (98 mg, 69% yield).

[0931] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.8 Hz, 1H), 8.13 (s, 1H), 7.93 (d, J = 1.8 Hz, 1H), 7.86 - 7.81 (m, 1H), 7.73 (br d, J = 7.7 Hz, 1H), 7.60 - 7.56 (m, 2H), 7.43 (t, J = 8.0 Hz, 1H), 7.05 (br d, J = 8.6 Hz, 2H), 6.96 (dd, J = 8.2, 2.4 Hz, 1H), 4.47 (q, J = 8.2 Hz, 2H), 3.68 - 3.59 (m, 4H), 3.27 - 3.19 (m, 4H), 1.50 (s, 9H).

[0932] 13 13C NMR (126 MHz, CDCl3) δ 157.96, 154.88, 151.08, 149.47, 145.28, 145.20, 144.24, 133.20, 132.44, 130.27, 129.52, 128.38, 123.59 (q, J = 278.8 Hz), 121.30, 116.93, 116.18, 114.38, 113.92, 80.18, 66.11 (q, J = 35.6 Hz), 49.15, 43.61, 28.60.

[0933] HRMS (APCI): Calculated for C 30 H 30 F3N3O4 [M + H] + = 554.2261; Found [M + H] + = 554.2255.

[0934] Preparation Example 116: 6-(4-(Piperazin-1-yl)phenyl)-3-(3-(2,2,2-trifluoroethoxy)phenyl]furo [3,2-b]pyridine

[0935]

[0936] Using 86 mg (0.155 mmol) of tert-butyl 4-(4-(3-(3-(2,2,2-trifluoroethoxy)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 115), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (MeOH) gave the compound as a white solid (50 mg, 71% yield).

[0937] 11H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.8 Hz, 1H), 8.13 (s, 1H), 7.93 (d, J = 1.8 Hz, 1H), 7.85 - 7.80 (m, 1H), 7.73 (br d, J = 7.7 Hz, 1H), 7.60 - 7.56 (m, 2H), 7.43 (t, J = 8.0 Hz, 1H), 7.07 - 7.03 (m, 2H), 6.96 (dd, J = 8.2, 2.4 Hz, 1H), 4.47 (q, J = 8.1 Hz, 2H), 3.28 - 3.22 (m, 4H), 3.11 - 3.03 (m, 4H).

[0938] 13 13C NMR (126 MHz, MeOD) δ 159.30, 153.13, 151.04, 147.73, 145.55, 144.89, 134.84, 133.47, 131.11, 129.82, 129.03, 122.74 (q, J = 268.4 Hz), 122.21, 121.31, 117.62, 117.32, 115.34, 114.78, 66.69 (q, J = 35.3 Hz), 50.64, 46.52.

[0939] HRMS (APCI): Calcd for C 25 H 22 F3N3O2 [M + H] + = 454.1737; Found [M + H] + = 454.1737.

[0940] Preparation Example 117: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-N-(p-tolyl)benzamide

[0941]

[0942] A compound was prepared by General Procedure A using 75 mg (0.323 mmol) of 3 - bromo - 6 - chlorofuro[3,2 - b]pyridine (Preparation Example 5) and 107 mg (0.419 mmol) of (3 - (p - tolylcarbamoyl)phenyl)boronic acid; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 9:1 to 4:1) gave the compound as a white solid (70 mg, 61% yield).

[0943] 11H NMR (500 MHz, CDCl3) δ 8.64 (d, J = 2.0 Hz, 1H), 8.57 - 8.54 (m, 1H), 8.26 - 8.22 (m, 1H), 8.21 (s, 1H), 7.93 (br s, 1H), 7.88 - 7.83 (m, 2H), 7.62 - 7.54 (m, 3H), 7.19 (d, J = 8.2 Hz, 2H), 2.36 (s, 3H).

[0944] 13 13C NMR (126 MHz, CDCl3) δ 165.53, 148.65, 146.23, 145.41, 144.10, 135.99, 135.56, 134.48, 130.72, 130.33, 129.77, 129.53, 128.07, 126.65, 125.80, 121.06, 120.52, 119.21, 21.07.

[0945] HRMS (APCI): Calcd for C 21 H 15 ClN2O2 [M + H] + = 363.0895; Found [M + H] + = 363.0893.

[0946] Preparation Example 118: tert-Butyl 4-(4-(3-(3-(p-tolylcarbamoyl)phenyl)furo[3,2-b] pyridin-6-yl)phenyl)piperazine-1-carboxylate

[0947]

[0948] Using 58 mg (0.160 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-N-(p-tolyl)benzamide (Preparation Example 117) and 81 mg (0.208 mmol) of 4-(4-Boc-piperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 h; flash chromatography (cyclohexane / EtOAc 2:3) gave the compound as a pale yellow solid (71 mg, 75% yield).

[0949] 11H NMR (500 MHz, CDCl3) δ 8.86 (d, J = 1.5 Hz, 1H), 8.56 (s, 1H), 8.26 (br d, J = 7.7 Hz, 1H), 8.20 - 8.13 (m, 2H), 7.91 (d, J = 1.4 Hz, 1H), 7.84 (br d, J = 7.7 Hz, 1H), 7.62 - 7.53 (m, 5H), 7.18 (d, J = 8.1 Hz, 2H), 7.03 (d, J = 8.6 Hz, 2H), 3.67 - 3.57 (m, 4H), 3.27 - 3.17 (m, 4H), 2.35 (s, 3H), 1.50 (s, 9H).

[0950] 13 13C NMR (126 MHz, CDCl3) δ 165.77, 154.87, 151.17, 149.49, 145.49, 145.00, 143.96, 135.90, 135.73, 134.28, 133.31, 131.21, 130.27, 129.68, 129.39, 129.18, 128.32, 126.54, 125.68, 120.94, 120.56, 116.82, 116.29, 80.16, 49.02, 43.74, 28.59, 21.05.

[0951] HRMS (APCI): Calcd for C 36 H 36 N4O4 [M + H] + = 589.2809; Found [M + H] + = 589.2812.

[0952] Preparation Example 119: 3-(6-(4-(Piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)-N-(p-meth ylphenyl)benzamide

[0953]

[0954] Using 70 mg (0.119 mmol) of tert-butyl (4-(3-(3-(p-tolylcarbamoyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 118), the compound was prepared by the general procedure D; the reaction time was 1 hour; flash chromatography (DCM / 7M NH3 in MeOH 97:3) gave the compound as an off-white solid (57 mg, 98% yield).

[0955] 11H NMR (500 MHz, DMSO) δ 10.24 (s, 1H), 8.96 (s, 1H), 8.92 (s, 1H), 8.73 (s, 1H), 8.48 (d, J = 7.8 Hz, 1H), 8.32 (s, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.73 - 7.62 (m, 5H), 7.18 (d, J = 8.2 Hz, 2H), 7.05 (d, J = 8.6 Hz, 2H), 3.17 - 3.10 (m, 4H), 2.92 - 2.81 (m, 4H), 2.29 (s, 3H).

[0956] 13 13C NMR (126 MHz, CDCl3) δ 166.09, 151.72, 149.57, 145.49, 144.88, 143.71, 136.14, 136.04, 134.07, 133.52, 130.82, 130.09, 129.60, 129.38, 128.45, 128.20, 127.08, 125.70, 121.08, 120.59, 116.37, 116.31, 49.92, 46.12, 21.03.

[0957] HRMS (APCI): Calculated for C 31 H 28 N4O2 [M + H] + = 489.2285; Found [M + H] + = 489.2282.

[0958] Preparation Example 120: N-Benzyl-3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzenesulfonamide

[0959]

[0960] Using 100 mg (0.430 mmol) of 3 - bromo - 6 - chlorofuro[3,2 - b]pyridine (Preparation Example 5) and 163 mg (0.560 mmol) of (3 - (N - benzylsulfamoyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 0:1) gave the compound as a white solid (86 mg, 50% yield).

[0961] 11H NMR (500 MHz, CDCl3) δ 8.63 (d, J = 2.0 Hz, 1H), 8.51 (t, J = 1.7 Hz, 1H), 8.38 - 8.34 (m, 1H), 8.19 (s, 1H), 7.89 - 7.85 (dd, J = 4.8, 1.6 Hz, 2H), 7.63 (t, J = 7.8 Hz, 1H), 7.29 - 7.21 (m, 5H), 4.78 (t, J = 6.0 Hz, 1H), 4.23 (d, J = 6.2 Hz, 2H).

[0962] 13 13C NMR (126 MHz, CDCl3) δ 148.60, 146.31, 145.68, 143.93, 140.87, 136.29, 131.47, 131.31, 129.89, 128.89, 128.22, 128.17, 128.10, 126.44, 125.51, 120.45, 119.12, 47.61.

[0963] Preparation Example 121: tert-Butyl 4-(4-(3-(3-(N-benzylaminosulfonyl)phenyl)furo[3,2-b]py ridin-6-yl)phenyl)piperazine-1-carboxylate

[0964]

[0965] Using 75 mg (0.189 mmol) of N-benzyl-3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzenesulfonamide (Preparation Example 120) and 95 mg (0.246 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 4:1 to 1:9) gave the compound as an off-white solid (70 mg, 59% yield).

[0966] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.8 Hz, 1H), 8.57 (s, 1H), 8.43 (br d, J = 7.6 Hz, 1H), 8.19 (s, 1H), 7.96 (d, J = 1.1 Hz, 1H), 7.89 - 7.84 (m, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.61 - 7.55 (m, 2H), 7.31 - 7.20 (m, 5H), 7.06 (d, J = 8.6 Hz, 2H), 4.89 (br s, 1H), 4.24 (d, J = 6.2 Hz, 2H), 3.77 - 3.52 (m, 4H), 3.32 - 3.16 (m, 4H), 1.50 (s, 9H).

[0967] 13 13C NMR (126 MHz, CDCl3) δ 154.89, 151.23, 149.52, 145.63, 145.36, 143.82, 140.76, 136.41, 133.53, 132.14, 131.30, 129.81, 129.19, 128.86, 128.37, 128.11, 126.15, 125.48, 120.37, 116.86, 116.29, 80.19, 49.03, 47.62, 43.78, 28.59.

[0968] HRMS (APCI): Calcd for C 35 H 36 N4O5S [M + H] + = 625.2479; Found [M + H] + = 625.2474.

[0969] Preparation Example 122: N-Benzyl-3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl) benzenesulfonamide

[0970]

[0971] A solution of 60 mg (0.096 mmol) of tert-butyl 4-(4-(3-(3-(N-benzylsulfamoyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 121) in MeOH (2.0 mL) was used to prepare the compound by the general procedure D; the reaction time was 2 h; flash chromatography (DCM / 7M NH3 in MeOH 24:1) gave the compound as a white solid (17 mg, 34% yield).

[0972] 1 1H NMR (500 MHz, DMSO) δ 8.99 - 8.92 (m, 2H), 8.76 (s, 1H), 8.46 (d, J = 7.8 Hz, 1H), 8.34 (s, 1H), 8.22 (br s, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.70 (t, J = 7.7 Hz, 3H), 7.30 - 7.17 (m, 5H), 7.06 (d, J = 8.7 Hz, 2H), 4.08 (s, 2H), 3.18 - 3.09 (m, 4H), 2.91 - 2.81 (m, 4H), 2.32 (br s, 1H).

[0973] 1313C NMR (126 MHz, CDCl3) δ 151.83, 149.57, 145.53, 145.41, 143.75, 140.74, 136.39, 133.70, 132.23, 131.35, 129.85, 128.90, 128.63, 128.30, 128.14, 126.15, 125.49, 120.40, 116.38, 116.23, 53.55, 50.07, 47.65, 46.24.

[0974] HRMS (APCI): Calcd for C 30 H 28 N4O3S [M + H] + = 525.1955; Found [M + H] + = 525.1958.

[0975] Preparation Example 123: N-Benzyl-3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzenesulfonamide

[0976]

[0977] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 128 mg (0.559 mmol) of (3-(methylsulfamoylmethyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 9:1 to 3:2) gave the compound as a white solid (139 mg, 96% yield).

[0978] 1 1H NMR (500 MHz, CDCl3) δ 8.61 (d, J = 2.0 Hz, 1H), 8.14 (s, 1H), 8.07 (s, 1H), 7.94 (d, J = 7.7 Hz, 1H), 7.84 (d, J = 2.0 Hz, 1H), 7.47 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 8.0 Hz, 1H), 4.81 (br s, 1H), 4.42 (d, J = 6.1 Hz, 2H), 2.94 (s, 3H).

[0979] 13 13C NMR (126 MHz, CDCl3) δ 148.58, 145.90, 145.39, 144.29, 137.61, 130.74, 129.64, 127.93, 127.59, 126.84, 126.66, 121.43, 119.00, 47.32, 41.42.

[0980] HRMS(APCI): Calculated value C 15 H 13 ClN2O3S[M+H] + = 337.0408; Measured value [M+H] + = 337.0408。

[0981] Preparation Example 124: tert-Butyl 4-(4-(3-(3-(methylsulfamidomethyl)phenyl)furo[3,2-b]py Pyridin-6-yl)phenyl)piperazine-1-carboxylate

[0982]

[0983] Using 120 mg (0.356 mmol) of N-benzyl-3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzenesulfonamide (Preparation Example 123) and 180 mg (0.463 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) gave a grayish-white solid compound (166 mg, 83% yield).

[0984] 1 H NMR(500 MHz, CDCl3) δ 8.86 (d, J = 1.9 Hz, 1H), 8.16 - 8.11 (m, 2H), 7.98 (br d, J = 7.7 Hz, 1H), 7.92 (d, J = 1.8 Hz, 1H), 7.59 - 7.54 (m, 2H), 7.48 (t, J = 7.7 Hz, 1H), 7.35 (br d, J = 7.7 Hz, 1H), 7.06 - 7.01 (m, 2H), 4.92 (br s, 1H), 4.43 (d, J = 6.1 Hz, 2H), 3.70 - 3.53 (m, 4H), 3.29 - 3.17 (m, 4H), 2.95 (s, 3H), 1.50 (s, 9H).

[0985] 13 C NMR(126 MHz, CDCl3) δ 154.87, 151.15, 149.46, 145.22, 145.05, 144.16, 137.57, 133.23, 131.34, 129.54, 129.28, 128.31, 127.33, 126.75, 126.67, 121.33, 116.83, 116.20, 80.17, 49.03, 47.35, 43.52, 41.34, 28.58。

[0986] HRMS(APCI): Calculated value C 30 H 34 N4O5S[M+H]+ = 563.2323; Measured value [M+H] + = 563.2326.

[0987] Preparation Example 125: N-(3-(6-(4-(Piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzyl) Methanesulfonamide

[0988]

[0989] Using 134 mg (0.290 mmol) of tert-butyl 4-(4-(3-(3-(methylsulfonylaminomethyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 124), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (MeOH) gave the compound as a white solid (90 mg, 67% yield).

[0990] 1 H NMR (500 MHz, DMSO) δ 8.94 (d, J = 1.9 Hz, 1H), 8.80 (s, 1H), 8.30 (d, J = 1.9 Hz, 1H), 8.22 (s, 1H), 8.16 (br d, J = 7.8 Hz, 1H), 7.72 - 7.58 (m, 2H), 7.60 (br s, 1H), 7.49 (t, J = 7.7 Hz, 1H), 7.38 (d, J = 7.7 Hz, 1H), 7.07 - 7.03 (m, 2H), 4.25 (d, J = 2.1 Hz, 2H), 3.18 - 3.10 (m, 4H), 2.92 (s, 3H), 2.89 - 2.80 (m, 4H), 2.27 (s, 1H).

[0991] 13 C NMR (126 MHz, CDCl3) δ 151.79, 149.54, 145.19, 145.13, 144.14, 137.47, 133.45, 131.54, 129.65, 128.78, 128.28, 127.32, 126.87, 126.71, 121.36, 116.38, 116.16, 50.11, 47.46, 46.27, 41.50.

[0992] HRMS (APCI): Calculated for C 25 H 26 N4O3S [M+H] + = 463.1798; Measured value [M+H] + = 463.1797.

[0993] Preparation Example 126: tert-Butyl (4-(6-chlorofuro[3,2-b]pyridin-3-yl)pyridin-2-yl)carbamateEster

[0994]

[0995] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 179 mg (0.559 mmol) of tert-butyl (4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamate, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc 1:4) gave the compound as a white solid (108 mg, 73% yield).

[0996] 1 1H NMR (500 MHz, CDCl3) δ 8.65 (d, J = 2.0 Hz, 1H), 8.49 - 8.44 (m, 2H), 8.40 (br d, J = 5.2 Hz, 1H), 8.33 (s, 1H), 7.88 (dd, J = 5.2, 1.3 Hz, 1H), 7.85 (d, J = 2.0 Hz, 1H), 1.57 (s, 9H).

[0997] 13 13C NMR (126 MHz, CDCl3) δ 152.93, 152.77, 148.65, 148.51, 147.76, 145.82, 143.90, 140.12, 128.15, 120.06, 119.11, 116.81, 109.36, 81.25, 28.54.

[0998] Preparation Example 127: tert-Butyl 4-(4-(3-(2-((tert-butoxycarbonyl)amino)pyridin-4-yl)furo[3, 2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate

[0999]

[1000] Using 53 mg (0.155 mmol) of tert-butyl (4-(6-chlorofuro[3,2-b]pyridin-3-yl)pyridin-2-yl)carbamate (Preparation Example 126) and 78 mg (0.202 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc 2:3) gave the compound as a white solid (80 mg, 90% yield).

[1001] 11H NMR (500 MHz, CDCl3) δ 8.91 (d, J = 1.9 Hz, 1H), 8.49 (s, 1H), 8.38 (d, J = 5.2 Hz, 1H), 8.33 (s, 1H), 7.96 (dd, J = 5.2, 1.3 Hz, 1H), 7.94 (d, J = 1.9 Hz, 1H), 7.88 (br s, 1H), 7.59 - 7.55 (m, 2H), 7.06 - 7.01 (m, 2H), 3.64 - 3.60 (m, 4H), 3.26 - 3.20 (m, 4H), 1.57 (s, 9H), 1.50 (s, 9H).

[1002] 13 13C NMR (126 MHz, CDCl3) δ 154.74, 152.53, 151.05, 149.42, 148.52, 146.91, 145.39, 143.69, 140.54, 133.31, 129.14, 128.23, 119.84, 119.09, 116.71, 116.12, 115.93, 109.10, 81.03, 80.03, 51.02, 48.90, 28.44, 28.37.

[1003] Preparation Example 128: tert-Butyl 4-(4-(3-(2-((tert-butoxycarbonyl)amino)pyridin-4-yl)furo[3, 2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate

[1004]

[1005] Using 53 mg (0.093 mmol) of tert-butyl 4-(4-(3-(2-(tert-butoxycarbonyl)amino)pyridin-4-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 127), the compound was prepared by General Procedure D; the reaction time was 1 hour; flash chromatography (DCM / 7M NH3 in MeOH 23:2) gave the compound as a white solid (47 mg, 98% yield).

[1006] 1 1H NMR (500 MHz, DMSO) δ 8.91 (d, J = 1.9 Hz, 1H), 8.87 (s, 1H), 8.32 (d, J = 1.9 Hz, 1H), 8.00 - 7.96 (m, 1H), 7.70 (d, J = 8.9 Hz, 2H), 7.48 (s, 1H), 7.16 (dd, J = 5.3, 1.4 Hz, 1H), 7.07 (d, J = 8.9 Hz, 2H), 6.01 (s, 2H), 3.21 - 3.15 (m, 4H), 2.95 - 2.89 (m, 4H).

[1007] 13 13C NMR (126 MHz, DMSO) δ 160.25, 150.97, 148.92, 148.21, 148.06, 144.31, 143.07, 138.51, 132.43, 127.80, 127.02, 118.75, 115.75, 115.64, 109.45, 105.12, 47.93, 44.73.

[1008] HRMS (APCI): Calculated for C 22 H 21 N5O [M+H] + = 372.1819; Found [M+H] + = 372.1818.

[1009] Preparation Example 129: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-N,N-dimethylaniline

[1010]

[1011] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 92 mg (0.558 mmol) of (3-(dimethylamino)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / DCM 1:1) gave the compound as an off-white solid (70 mg, 60% yield).

[1012] 1 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J = 2.0 Hz, 1H), 8.09 (s, 1H), 7.81 (d, J = 2.0 Hz, 1H), 7.47 (s, 1H), 7.38 - 7.28 (m, 2H), 6.77 (d, J = 7.5 Hz, 1H), 3.03 (s, 6H).

[1013] 13 13C NMR (126 MHz, CDCl3) δ 151.12, 148.49, 145.67, 145.24, 144.79, 130.56, 129.68, 127.49, 122.72, 118.67, 115.68, 112.57, 111.72, 40.81.

[1014] HRMS (APCI): Calculated for C 15 H 13 ClN2O [M+H] + = 273.0789; Found [M+H] + = 273.0788.

[1015] Preparation Example 130: tert-Butyl 4-(4-(3-(3-(dimethylamino)phenyl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[1016]

[1017] Using 50 mg (0.183 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-N,N-dimethylaniline (Preparation Example 129) and 92 mg (0.238 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 4:1 to 7:3) gave the compound as a white solid (86 mg, 94% yield).

[1018] 1 H NMR (500 MHz, CDCl3) δ 8.79 (d, J = 1.9 Hz, 1H), 8.01 (s, 2H), 7.81 (d, J = 1.9 Hz, 1H), 7.51 - 7.47 (m, 2H), 7.45 (br s, 1H), 7.33 - 7.24 (m, 2H), 6.97 - 6.92 (m, 2H), 6.71 - 6.67 (m, 1H), 3.55 - 3.49 (m, 4H), 3.16 - 3.10 (m, 4H), 2.95 (s, 6H), 1.42 (s, 9H).

[1019] 13 C NMR (126 MHz, CDCl3) δ 154.86, 151.09, 151.01, 149.35, 145.01, 144.75, 132.77, 131.22, 129.66, 129.62, 128.29, 127.33, 122.62, 119.28, 116.84, 115.91, 112.41, 111.79, 80.11, 49.08, 43.52, 40.87, 28.57.

[1020] HRMS (APCI): Calcd for C 30 H 34 N4O3 [M + H] + = 499.2704; Found [M + H] + = 499.2708.

[1021] Preparation Example 131: N,N-Dimethyl-3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)aniline

[1022]

[1023] Using 52 mg (0.104 mmol) of tert-butyl 4-(4-(3-(2-(dimethylamino)pyridin-4-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 129), the compound was prepared by the general procedure D; the reaction time was 1 hour; flash chromatography (DCM / 7M NH3 in MeOH, 19:1) gave the compound as a white solid (38 mg, 92% yield).

[1024] 1 H NMR (500 MHz, DMSO) δ 8.92 (d, J = 1.9 Hz, 1H), 8.78 (s, 1H), 8.26 (d, J = 1.9 Hz, 1H), 7.72 - 7.66 (m, 2H), 7.66 - 7.61 (m, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.28 (t, J = 7.9 Hz, 1H), 7.07 - 7.02 (m, 2H), 6.74 (dd, J = 8.2, 2.4 Hz, 1H), 3.16 - 3.09 (m, 4H), 2.98 (s, 6H), 2.89 - 2.82 (m, 4H).

[1025] 13 C NMR (126 MHz, DMSO) δ 151.31, 150.67, 148.83, 146.45, 144.12, 143.56, 132.09, 130.85, 129.07, 127.65, 126.79, 120.79, 115.41, 115.37, 114.83, 111.81, 110.63, 48.90, 45.48, 40.18.

[1026] HRMS (APCI): Calcd for C 25 H 26 N4O [M + H] + = 399.2179; Found [M + H] + = 399.2182.

[1027] Preparation Example 132: (3-(6-Chlorofuro[3,2-b]pyridin-3-yl)phenyl)(phenyl)methanone

[1028]

[1029] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 179 mg (0.561 mmol) of phenyl(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanone, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, 97:3) gave the compound as an off-white solid (113 mg, 79% yield).

[1030] 1 H NMR (500 MHz, CDCl3) δ 8.59 (d, J = 2.0 Hz, 1H), 8.40 - 8.34 (m, 2H), 8.16 (s, 1H), 7.88 - 7.84 (m, 2H), 7.83 (d, J = 2.0 Hz, 1H), 7.78 - 7.74 (m, 1H), 7.62 - 7.57 (m, 2H), 7.52 - 7.47 (m, 2H).

[1031] 13 C NMR (126 MHz, CDCl3) δ 196.55, 148.57, 146.04, 145.55, 144.29, 138.39, 137.63, 132.74, 131.27, 130.43, 130.35, 129.74, 129.01, 128.52, 128.50, 127.99, 121.27, 118.98.

[1032] HRMS (APCI): Calcd for C 20 H 12 ClNO2 [M + H] + = 334.0629; Found [M + H] + = 334.0631.

[1033] Preparation Example 133: (3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl) phenyl(phenyl)methanone

[1034]

[1035] Using 80 mg (0.240 mmol) of (3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)(phenyl)methanone (Preparation Example 132) and 94 mg (0.311 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 1 hour; flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1) gave the compound as an off-white solid (109 mg, 96% yield).

[1036] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.9 Hz, 1H), 8.51 - 8.47 (m, 1H), 8.45 (t, J = 1.5 Hz, 1H), 8.19 (s, 1H), 7.96 (d, J = 1.9 Hz, 1H), 7.94 - 7.89 (m, 2H), 7.79 (dt, J = 7.7, 1.3 Hz, 1H), 7.67 - 7.57 (m, 4H), 7.56 - 7.50 (m, 2H), 7.11 - 7.04 (m, 2H), 3.42 - 3.33 (m, 4H), 2.72 (br s, 4H), 2.46 (s, 3H).

[1037] 13 13C NMR (126 MHz, CDCl3) δ 196.69, 151.24, 149.49, 145.31, 144.13, 138.32, 137.74, 133.45, 132.66, 131.39, 131.14, 130.36, 129.45, 128.98, 128.80, 128.48, 128.30, 121.19, 116.34, 116.12, 55.19, 48.82, 46.32.

[1038] HRMS (APCI): Calculated for C 31 H 27 N3O2 [M + H] + = 474.2176; Found [M + H] + = 474.2180.

[1039] Preparation Example 134: tert-Butyl (3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzyl)carbamate

[1040]

[1041] Using 100 mg (0.43 mmol) of 3 - bromo - 6 - chlorofuro[3,2 - b]pyridine (Preparation Example 5) and 141 mg (0.56 mmol) of (3 - (((tert - butoxycarbonyl)amino)methyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 97:3 to 9:1) gave the compound as a yellow oil (148 mg, 96% yield).

[1042] 11H NMR (500 MHz, CDCl3) δ 8.61 (d, J = 2.0 Hz, 1H), 8.10 (s, 1H), 7.95 - 7.91 (m, 2H), 7.82 (d, J = 2.0 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 7.30 (br d, J = 7.6 Hz, 1H), 4.93 (br s, 1H), 4.40 (d, J = 5.4 Hz, 2H), 1.48 (s, 9H).

[1043] 13 13C NMR (126 MHz, CDCl3) δ 156.09, 148.53, 145.76, 145.33, 144.46, 139.83, 130.32, 129.36, 127.77, 127.33, 126.32, 121.83, 118.86, 79.71, 44.88, 28.58.

[1044] Preparation Example 135: tert-Butyl (3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin- 3-yl)benzyl)carbamate

[1045]

[1046] Using 86 mg (0.240 mmol) of tert-butyl (3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzyl)carbamate (Preparation Example 134) and 94 mg (0.311 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 1 hour; flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1) gave the compound as an off-white solid (113 mg, 94% yield).

[1047] 1 1H NMR (500 MHz, CDCl3) δ 8.80 (d, J = 1.9 Hz, 1H), 8.03 (s, 1H), 7.97 - 7.87 (m, 2H), 7.85 (d, J = 1.9 Hz, 1H), 7.53 - 7.46 (m, 2H), 7.39 (t, J = 7.7 Hz, 1H), 7.23 (br d, J = 7.6 Hz, 1H), 7.0 - 6.95 (m, 2H), 4.85 (br s, 1H), 4.34 (d, J = 5.3 Hz, 2H), 3.28 - 3.19 (m, 4H), 2.59 - 2.51 (m, 4H), 2.31 (s, 3H), 1.41 (s, 9H).

[1048] 1313C NMR (126 MHz, CDCl3) δ 155.94, 151.02, 149.30, 144.97, 144.87, 144.17, 139.52, 133.08, 130.89, 129.19, 128.78, 128.13, 126.93, 126.22, 121.59, 116.20, 115.89, 79.50, 55.01, 48.64, 46.12, 44.82, 28.44。

[1049] HRMS (APCI): Calcd for C 30 H 34 N4O3 [M+H] + = 499.2704; Found [M+H] + = 499.2706。

[1050] Preparation Example 136: (3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl) phenyl)methanamine

[1051]

[1052] Using 97 mg (0.195 mmol) of tert-butyl (3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzyl)carbamate (Preparation Example 135), the compound was prepared by the general procedure D; the reaction time was 1 hour; flash chromatography (DCM / MeOH, gradient from 97:3 to 19:1) gave the compound as an off-white solid (60 mg, 77% yield).

[1053] 1 1H NMR (500 MHz, CDCl3) δ 8.79 (d, J = 1.9 Hz, 1H), 8.02 (s, 1H), 7.94 (br s, 1H), 7.87 (br d, J = 7.7 Hz, 1H), 7.82 (d, J = 1.9 Hz, 1H), 7.51 - 7.45 (m, 2H), 7.36 (t, J = 7.6 Hz, 1H), 7.22 (br d, J = 7.7 Hz, 1H), 7.00 - 6.92 (m, 2H), 3.88 (s, 2H), 3.25 - 3.17 (m, 4H), 2.57 - 2.49 (m, 4H), 2.28 (s, 3H).

[1054] 1313C NMR (126 MHz, CDCl3) δ 151.19, 149.48, 145.13, 145.01, 144.40, 144.04, 133.20, 130.95, 129.25, 128.93, 128.28, 126.68, 126.02, 125.83, 121.93, 116.35, 116.04, 55.19, 48.83, 46.73, 46.32.

[1055] HRMS (APCI): Calcd for C 25 H 26 N4O [M + H] + = 399.2179; Found [M + H] + = 399.2180.

[1056] Preparation Example 137: N-(3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzyl)acetamide

[1057]

[1058] TEA (0.037 mL, 0.263 mmol) and acetic anhydride (0.053 mL, 0.525 mmol) were added to a solution of 42 mg (0.105 mmol) of (3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)phenyl)methanamine (Preparation Example 136) in DCM (2 mL), and the mixture was stirred at 25 °C for 3 h. The volatiles were evaporated in vacuo, and the residue was purified by flash chromatography (cyclohexane / EtOAc, 1:1). A pale gray solid product (44 mg, 94% yield) was obtained.

[1059] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.9 Hz, 1H), 8.14 (s, 1H), 8.04 (br s, 1H), 8.00 (br d, J = 7.7 Hz, 1H), 7.95 (d, J = 1.9 Hz, 1H), 7.62 - 7.57 (m, 2H), 7.49 (t, J = 7.7 Hz, 1H), 7.33 (br d, J = 7.7 Hz, 1H), 7.09 - 7.05 (m, 2H), 5.88 (br s, 1H), 4.56 (d, J = 5.7 Hz, 2H), 3.42 - 3.28 (m, 4H), 2.73 - 2.60 (m, 4H), 2.42 (s, 3H), 2.08 (s, 3H).

[1060] 1313C NMR (126 MHz, CDCl3) δ 170.02, 151.21, 149.49, 145.14, 145.10, 144.26, 139.00, 133.31, 131.21, 129.47, 128.86, 128.29, 127.49, 126.82, 126.54, 121.62, 116.36, 116.11, 55.16, 48.79, 46.28, 44.05, 23.49。

[1061] HRMS (APCI): Calculated for C 27 H 28 N4O2 [M + H] + = 441.2285; Found [M + H] + = 441.2288。

[1062] Preparation Example 138: 1-(3-Bromophenyl)-N-ethylmethanesulfonamide

[1063]

[1064] A solution of 0.75 mL (1.50 mmol; 2.0 M in THF) of ethylamine and 0.21 mL (1.51 mmol) of TEA was added to a solution of 404 mg (1.50 mmol) of (3-bromophenyl) methanesulfonyl chloride in DCM (5.0 mL). The resulting mixture was stirred at 25 °C for 1.5 h and then the solvent was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 4:1 to 1:1). A white solid product was obtained (398 mg, 95% yield).

[1065] 1 1H NMR (500 MHz, CDCl3) δ 7.55 (t, J = 1.7 Hz, 1H), 7.53 - 7.50 (m, 1H), 7.34 (br d, J = 7.7 Hz, 1H), 7.26 (t, J = 7.8 Hz, 1H), 4.19 (s, 2H), 4.09 (br s, 1H), 3.10 - 3.02 (m, 2H), 1.16 (t, J = 7.2 Hz, 3H).

[1066] 13 13C NMR (126 MHz, CDCl3) δ 133.68, 132.03, 131.83, 130.46, 129.42, 122.84, 58.46, 38.98, 16.04。

[1067] HRMS (APCI): Calculated for C9H 12 BrNO2S [M + NH4] += 295.0110; Measured value [M+NH4] + = 295.0107.

[1068] Preparation Example 139: N-Ethyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl] methanesulfonamide

[1069]

[1070] Pd(dppf)Cl2 (17.4 mg, 0.024 mmol) was added to a degassed suspension of 1-(3-bromophenyl)-N-ethylmethanesulfonamide (Preparation Example 138, 387 mg, 1.19 mmol), KOAc (467 mg, 4.76 mmol), and (BPin)2 (423 mg, 1.67 mmol) in 1,4-dioxane (5.1 mL), and the mixture was stirred at 70 °C; the progress of the reaction was followed by TLC. After consumption of the starting material (17 h), the mixture was cooled to 25 °C, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, gradient from 19:1 to 1:1). A colorless oil product was obtained (362 mg, 94% yield).

[1071] 1 H NMR (500 MHz, CDCl3) δ 7.87 - 7.79 (m, 2H), 7.58 - 7.51 (m, 1H), 7.45 - 7.39 (m, 1H), 4.27 (s, 2H), 4.01 (t, J = 5.5 Hz, 1H), 3.13 - 3.00 (m, 2H), 1.37 (s, 12H), 1.15 (t, J = 7.2 Hz, 3H).

[1072] 13 C NMR (126 MHz, CDCl3) δ 137.03, 135.23, 133.50, 130.74, 129.04, 128.41, 84.18, 58.82, 38.95, 25.04, 15.88.

[1073] Preparation Example 140: 1-(3-(6-Chlorofuro[3,2-b]pyridin-3-yl)phenyl)-N-ethylmethanesulfonamide

[1074]

[1075] Using 50 mg (0.215 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 91 mg (0.279 mmol) of N-ethyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (Preparation Example 137), the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, 1:1) gave the compound as an off-white solid (70 mg, 91% yield).

[1076] 1 H NMR (500 MHz, CDCl3) δ 8.58 (d, J = 2.0 Hz, 1H), 8.15 - 8.09 (m, 2H), 8.01 - 7.96 (m, 1H), 7.82 (d, J = 2.0 Hz, 1H), 7.48 (t, J = 7.7 Hz, 1H), 7.43 - 7.35 (m, 1H), 4.31 (s, 2H), 3.18 - 3.07 (m, 2H), 1.16 (t, J = 7.2 Hz, 3H).

[1077] 13 C NMR (126 MHz, CDCl3) δ 148.42, 145.74, 145.24, 144.15, 130.55, 130.30, 130.24, 129.41, 129.21, 127.80, 127.25, 121.13, 118.85, 58.54, 38.83, 15.87.

[1078] HRMS (APCI): Calcd for C 16 H 15 ClN2O3S [M + H] + = 351.0565; Found [M + H] + = 351.0569.

[1079] Preparation Example 141: N-Ethyl-1-(3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]py ridin-3-yl)phenyl)methanesulfonamide

[1080]

[1081] Using 55 mg (0.157 mmol) of 1-(3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)-N-ethylmethanesulfonamide (Preparation Example 140) and 63 mg (0.208 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 1 hour; flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1) gave the compound as a white solid (54 mg, 69% yield).

[1082] 1 H NMR (500 MHz, DMSO) δ 8.93 (d, J = 1.9 Hz, 1H), 8.80 (s, 1H), 8.31 (d, J = 1.9 Hz, 1H), 8.28 - 8.25 (m, 1H), 8.25 - 8.20 (m, 1H), 7.72 - 7.68 (m, 2H), 7.51 (t, J = 7.7 Hz, 1H), 7.40 - 7.36 (m, 1H), 7.10 - 7.05 (m, 3H), 4.38 (s, 2H), 3.25 - 3.21 (m, 4H), 3.05 - 2.96 (m, 2H), 2.50 - 2.45 (m, 4H), 2.24 (s, 3H), 1.07 (t, J = 7.2 Hz, 3H).

[1083] 13 C NMR (126 MHz, DMSO) δ 150.74, 148.86, 146.64, 144.24, 143.23, 132.33, 130.93, 130.49, 130.00, 128.82, 128.61, 127.74, 126.86, 126.10, 119.81, 115.59, 115.52, 57.27, 54.44, 47.62, 45.70, 37.59, 15.49.

[1084] HRMS (APCI): Calculated for C 27 H 30 N4O3S [M + H] + = 491.2111; Found [M + H] + = 491.2110.

[1085] Preparation Example 142: 1-(3-Bromophenyl)-N,N-dimethylmethanesulfonamide

[1086]

[1087] A solution of dimethylamine (2.0 M in THF; 0.5 mL, 1.00 mmol) and TEA (0.14 mL, 1.00 mmol) was added to a solution of (3-bromophenyl)methanesulfonyl chloride (270 mg, 1.00 mmol) in DCM (5.0 mL). The resulting mixture was stirred at 25 °C for 2 h and then the solvent was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc 1:1). A white solid product was obtained (261 mg, 94% yield).

[1088] 1 1H NMR (500 MHz, CDCl3) δ 7.54 (t, J = 1.7 Hz, 1H), 7.51 - 7.47 (m, 1H), 7.34 (br d, J = 7.8 Hz, 1H), 7.24 (t, J = 7.8 Hz, 1H), 4.15 (s, 2H), 2.76 (s, 6H).

[1089] 13 13C NMR (126 MHz, CDCl3) δ 133.60, 131.88, 131.41, 130.37, 129.40, 122.72, 55.18, 37.88.

[1090] Preparation Example 143: N,N-Dimethyl-1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl]methanesulfonamide

[1091]

[1092] Pd(dppf)Cl2 (8.9 mg, 0.012 mmol) was added to a degassed suspension of 1-(3-bromophenyl)-N,N-dimethylmethanesulfonamide (Preparation Example 142, 170 mg, 0.611 mmol), KOAc (239 mg, 2.440 mmol) and (BPin)2 (217 mg, 0.855 mmol) in 1,4-dioxane (2.6 mL), and the mixture was stirred at 70 °C; the progress of the reaction was followed by TLC. After consumption of the starting material (17 h), the mixture was cooled to 25 °C, filtered, and the solvent was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, 7:3). A colorless oil product was obtained (115 mg, 58% yield).

[1093] 1 1H NMR (500 MHz, CDCl3) δ 7.82 - 7.76 (m, 2H), 7.56 - 7.51 (m, 1H), 7.41 - 7.36 (m, 1H), 4.23 (s, 2H), 2.73 (s, 6H), 1.35 (s, 12H).

[1094] 13 13C NMR (126 MHz, CDCl3) δ 137.02, 135.17, 133.51, 129.83 (d, J = 233.4), 128.57, 128.31, 84.14, 55.97, 37.93, 25.02.

[1095] Preparation Example 144: 1-(3-(6-Chlorofuro[3,2-b]pyridin-3-yl)phenyl)-N,N-dimethylmethanesulf amide

[1096]

[1097] Using 50 mg (0.215 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 91 mg (0.280 mmol) of N,N-dimethyl-1-(3-(4,4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (Preparation Example 143), the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc 1:1) gave a grayish-white solid compound (68 mg, 88% yield).

[1098] 1 1H NMR (500 MHz, CDCl3) δ 8.60 (d, J = 2.0 Hz, 1H), 8.16 - 8.13 (m, 2H), 8.00 (d, J = 7.7 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.49 (t, J = 7.7 Hz, 1H), 7.44 - 7.40 (m, 1H), 4.32 (s, 2H), 2.79 (s, 6H).

[1099] 13 13C NMR (126 MHz, CDCl3) δ 148.50, 145.91, 145.32, 144.23, 130.59, 130.32, 129.92, 129.43, 127.84, 127.24, 121.14, 118.92, 56.11, 37.90.

[1100] HRMS (APCI): Calcd for C 16 H 15 ClN2O3S [M + H] + = 351.0565; Found [M + H] + = 351.0562.

[1101] Preparation Example 145: N,N-Dimethyl-1-(3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2- b]pyridin-3-yl)phenyl)methanesulfonamide

[1102]

[1103] Using 40 mg (0.114 mmol) of 1-(3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)-N,N-dimethylmethanesulfonamide (Preparation Example 144) and 43 mg (0.142 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (MeOH) gave the compound as a white solid (50 mg, 93% yield).

[1104] 1 H NMR (500 MHz, CDCl3) δ 8.87 (d, J = 1.9 Hz, 1H), 8.24 - 8.19 (m, 1H), 8.15 (s, 1H), 8.09 - 8.04 (m, 1H), 7.93 (d, J = 1.9 Hz, 1H), 7.60 - 7.55 (m, 2H), 7.50 (t, J = 7.7 Hz, 1H), 7.45 - 7.40 (m, 1H), 7.07 - 7.02 (m, 2H), 4.35 (s, 2H), 3.37 - 3.29 (m, 4H), 2.80 (s, 6H), 2.68 - 2.61 (m, 4H), 2.40 (s, 3H).

[1105] 13 C NMR (126 MHz, CDCl3) δ 151.12, 149.50, 145.17, 145.15, 144.17, 136.30, 133.36, 131.38, 130.07, 129.91, 129.50, 129.45, 128.92, 128.30, 127.32, 121.15, 116.42, 116.12, 56.42, 55.08, 48.68, 46.16, 37.98.

[1106] HRMS (APCI): Calcd for C 27 H 30 N4O3S [M + H] + = 491.2111; Found [M + H] + = 491.2114.

[1107] Preparation Example 146: 6-Chloro-3-(3-(methylthio)phenyl)furo[3,2-b]pyridine

[1108]

[1109] Using 300 mg (1.29 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 282 mg (1.68 mmol) of (3-(methylthio)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 99:1 to 97:3) gave the compound as an off-white oil (222 mg, 79% yield).

[1110] 1 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J = 2.0 Hz, 1H), 8.11 (s, 1H), 7.96 (t, J = 1.7 Hz, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.82 - 7.78 (m, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.29 - 7.26 (m, 1H), 2.55 (s, 3H).

[1111] 13 13C NMR (126 MHz, CDCl3) δ 148.53, 145.82, 145.39, 144.37, 139.43, 130.63, 129.42, 127.82, 126.36, 125.43, 124.01, 121.60, 118.89, 16.10.

[1112] HRMS (APCI): Calcd for C 14 H 10 ClNOS [M+H] + = 276.0244; Found [M+H] + = 276.0244.

[1113] Preparation Example 147: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(3-(methylthio)phenyl)furo [3,2-b]pyridine

[1114]

[1115] Using 172 mg (0.624 mmol) of 6-chloro-3-(3-(methylthio)phenyl)furo[3,2-b]pyridine (Preparation Example 146) and 244 mg (0.807 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 1 hour; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a white solid (213 mg, 83% yield).

[1116] 11H NMR (500 MHz, CDCl3) δ 8.88 (d, J = 1.9 Hz, 1H), 8.11 (s, 1H), 8.01 (t, J = 1.7 Hz, 1H), 7.92 (br d, J = 1.9 Hz, 1H), 7.90 - 7.87 (m, 1H), 7.60 - 7.55 (m, 2H), 7.41 (t, J = 7.8 Hz, 1H), 7.29 - 7.26 (m, 1H), 7.07 - 7.03 (m, 2H), 3.34 - 3.28 (m, 4H), 2.64 - 2.58 (s, 4H), 2.57 (s, 3H), 2.38 (s, 3H).

[1117] 13 13C NMR (126 MHz, CDCl3) δ 151.20, 149.45, 145.21, 145.05, 144.27, 139.23, 133.26, 131.39, 129.39, 128.89, 128.28, 126.14, 125.47, 124.13, 121.54, 116.33, 116.01, 55.19, 48.83, 46.32, 16.18.

[1118] HRMS (APCI): Calcd for C 25 H 25 N3OS [M + H] + = 416.1791; Found [M + H] + = 416.1792.

[1119] Preparation Example 148: 6-Chloro-3-(thiophen-3-yl)furo[3,2-b]pyridine

[1120]

[1121] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 72 mg (0.559 mmol) of thiophene-3-ylboronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 49:1) gave the compound as a white solid (87 mg, 86% yield).

[1122] 1 1H NMR (500 MHz, CDCl3) δ 8.60 (d, J = 2.0 Hz, 1H), 8.24 (dd, J = 2.9, 1.1 Hz, 1H), 8.06 (s, 1H), 7.79 (d, J = 2.0 Hz, 1H), 7.51 (dd, J = 5.0, 1.1 Hz, 1H), 7.43 (dd, J = 5.0, 3.0 Hz, 1H).

[1123] 13 C NMR (126 MHz, CDCl3) δ 148.20, 145.31, 145.06, 144.37, 129.74, 127.80, 126.21, 125.76, 123.08, 118.70, 117.98.

[1124] HRMS (APCI): Calculated for C 11 H6ClNOS [M + H] + = 235.9931; Found [M + H] + = 235.9934.

[1125] Preparation Example 149: 6-Phenyl-3-(thiophen-3-yl)furo[3,2-b]pyridine

[1126]

[1127] Using 54 mg (0.232 mmol) of 6-chloro-3-(thiophen-3-yl)furo[3,2-b]pyridine (Preparation Example 148) and 61 mg (0.299 mmol) of 4,4,5,5-tetramethyl-2-phenyl-1,3,2-dioxaborolane, the compound was prepared by the general procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 49:1) gave the compound as a white solid (50 mg, 78% yield).

[1128] 1 H NMR (500 MHz, CDCl3) δ 8.91 (d, J = 1.9 Hz, 1H), 8.31 (dd, J = 3.0, 1.2 Hz, 1H), 8.12 (s, 1H), 7.96 (d, J = 1.9 Hz, 1H), 7.68 - 7.63 (m, 2H), 7.58 (dd, J = 5.0, 1.2 Hz, 1H), 7.54 - 7.49 (m, 2H), 7.46 - 7.40 (m, 2H).

[1129] 13 C NMR (126 MHz, CDCl3) δ 149.02, 145.55, 145.11, 144.84, 138.37, 133.51, 130.37, 129.33, 128.12, 127.71, 126.16, 125.95, 122.87, 118.03, 116.83.

[1130] HRMS (APCI): Calculated for C 17 H 11 NOS [M + H] += 278.0634; Measured value [M+H] + = 278.0634.

[1131] Preparation Example 150: 2-(3-(6-Chlorofuro[3,2-b]pyridin-3-yl)phenyl)-N-ethylethanamide

[1132]

[1133] Using 120 mg (0.516 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 195 mg (0.671 mmol) of N-ethyl-2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide, the compound was prepared by General Procedure A; the reaction time was 4 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g) and the filtrate was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 9:1 to 1:1). A pale gray solid product (133 mg, 82%) was obtained.

[1134] 1 1H NMR (500 MHz, chloroform-d) δ 8.64 (d, J = 2.0 Hz, 1H), 8.15 (s, 1H), 7.93 - 8.01 (m, 2H), 7.87 (d, J = 2.0 Hz, 1H), 7.50 (dd, J = 7.6, 7.6 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 5.47 (s, 1H), 3.68 (s, 2H), 3.25 - 3.34 (m, 2H), 1.11 (t, J = 7.2 Hz, 3H).

[1135] 13 13C NMR (126 MHz, chloroform-d) δ 148.43, 145.74, 145.19, 144.17, 135.75, 130.57, 129.60, 129.10, 128.22, 127.75, 126.10, 121.46, 118.88, 43.99, 34.62, 14.78.

[1136] Preparation Example 151: tert-Butyl 4-(4-(3-(3-(2-(ethylamino)-2-oxoethyl)phenyl)furo[3,2- b]pyridin-6-yl)phenyl)piperazine-1-carboxylate

[1137]

[1138] Using 133 mg (0.423 mmol) of 2-(3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)-N-ethylacetamide (Preparation Example 150) and 214 mg (0.550 mmol) of tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate, the compound was prepared by General Procedure B; the reaction time was 2 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was evaporated in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 7:3 to 1:9) to give the product as an off-white solid (200 mg, 87%).

[1139] 1 1H NMR (500 MHz, chloroform-d) δ 8.90 (d, J = 1.9 Hz, 1H), 8.15 (s, 1H), 8.05 (ddd, J = 1.5, 1.5, 7.6 Hz, 1H), 8.01 (dd, J = 1.8, 1.8 Hz, 1H), 7.96 (d, J = 1.9 Hz, 1H), 7.58 - 7.62 (m, 2H), 7.51 (dd, J = 7.7, 7.7 Hz, 1H), 7.30 (ddd, J = 1.4, 1.4, 7.6 Hz, 1H), 7.05 - 7.09 (m, 2H), 5.53 (s, 1H), 3.69 (s, 2H), 3.61 - 3.66 (m, 4H), 3.28 - 3.33 (m, 2H), 3.22 - 3.28 (m, 4H), 1.52 (s, 9H), 1.10 (t, J = 7.2 Hz, 3H).

[1140] 13 13C NMR (126 MHz, CDCl3) δ 170.68, 170.60, 154.77, 151.01, 149.34, 145.07, 144.89, 144.06, 135.69, 133.08, 131.23, 129.58, 129.23, 128.82, 128.31, 126.12, 121.35, 116.73, 116.12, 80.02, 48.94, 44.00, 34.59, 34.45, 28.45, 14.76.

[1141] Preparation Example 152: N-Ethyl-2-(3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)phenyl]ethanamide

[1142]

[1143] At 0 °C (ice bath), under argon, 6.5 mL of a 4 M HCl 1,4-dioxane solution was added to a heterogeneous mixture of 200 mg (0.370 mmol) of tert-butyl 4-(4-(3-(3-(2-(ethylamino)-2-oxoethyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 151) in 15.0 mL of MeOH. The mixture was stirred at 0 °C for 90 minutes. The ice bath was removed and the mixture was stirred at 25 °C for an additional 4.5 hours. The reaction mixture was concentrated in vacuo, 500 mg (5.952 mmol) of solid sodium bicarbonate was added to the residue, and the mixture was stirred in DCM / MeOH 5:1 (12 mL) for 2 hours. The mixture was filtered through a 535 and SiO2 (1:1; 8 g) pad and the pad was washed with 50 mL of a DCM / MeOH 5:1 mixture. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) to afford the product as an off-white solid (116 mg, 71%).

[1144] 1 1H NMR (500 MHz, DMSO-d6) δ 8.95 (d, J = 2.0 Hz, 1H), 8.80 (s, 1H), 8.33 (d, J = 1.9 Hz, 1H), 8.04 - 8.15 (m, 3H), 7.73 - 7.77 (m, 2H), 7.43 (dd, J = 7.7, 7.7 Hz, 1H), 7.28 (ddd, J = 1.4, 1.4, 7.6 Hz, 1H), 7.11 - 7.15 (m, 2H), 3.48 (s, 2H), 3.37 - 3.43 (m, 4H), 3.14 - 3.20 (m, 4H), 3.06 - 3.13 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H).

[1145] 13 13C NMR (126 MHz, methanol-d4) δ 172.33, 150.38, 149.54, 146.17, 144.06, 143.91, 136.26, 133.05, 130.56, 129.73, 128.61, 128.08, 127.87, 127.71, 125.49, 121.25, 116.78, 116.06, 46.73, 43.74, 42.55, 34.08, 13.36.

[1146] HRMS (APCI): Calcd for C 27 H 28 N4O2 [M + H] + = 441.2285; Found [M + H]+ = 441.2286.

[1147] Preparation Example 153: 2-(3-(6-Chlorofuro[3,2-b]pyridin-3-yl)phenyl)ethanamide

[1148]

[1149] Using 300 mg (0.950 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 323 mg (1.235 mmol) of 2-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide, the compound was prepared by General Procedure A; the reaction time was 6.5 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (EtOAc) gave the product as an off-white solid (220 mg, 80%).

[1150] 1 1H NMR (500 MHz, CDCl3) δ 8.63 (d, J = 2.1 Hz, 1H), 8.15 (s, 1H), 7.98 (dd, J = 1.7, 8.8 Hz, 2H), 7.85 (d, J = 2.0 Hz, 1H), 7.49 (dd, J = 7.6, 7.6 Hz, 1H), 7.32 (ddd, J = 1.4, 1.4, 7.6 Hz, 1H), 5.57 (bs, 2H), 3.70 (s, 2H).

[1151] 13 13C NMR (126 MHz, CDCl3) δ 173.15, 148.41, 145.73, 145.22, 144.14, 135.57, 130.67, 129.62, 128.99, 128.09, 127.73, 126.17, 121.36, 118.84, 43.38.

[1152] Preparation Example 154: 2-(3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)phenyl]ethanamide

[1153]

[1154] Using 80 mg (0.279 mmol) of 2-(3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)acetamide (Preparation Example 153) and 110 mg (0.363 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 3 hours. The reaction mixture was filtered through The mixture of 535 and SiO2 (1:1, 8 g) was subjected to hot filtration, and the filtrate was concentrated under vacuum. Flash chromatography (EtOAc / MeOH, gradient from 1:0 to 7:3) gave the product as an off-white solid (23 mg, 17% yield).

[1155] 1 1H NMR (500 MHz, DMSO-d6) δ 8.94 (d, J = 1.9 Hz, 1H), 8.79 (s, 1H), 8.31 (d, J = 1.9 Hz, 1H), 8.08 - 8.15 (m, 2H), 7.71 (d, J = 8.5 Hz, 2H), 7.48 (s, 1H), 7.43 (dd, J = 7.6, 7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.09 (d, J = 8.5 Hz, 2H), 6.89 (s, 1H), 3.48 (s, 2H), 3.23 - 3.29 (m, 4H), 2.53 - 2.63 (m, 4H), 2.31 (s, 3H).

[1156] 13 13C NMR (126 MHz, DMSO-d6) δ 172.56, 151.03, 149.34, 147.04, 144.74, 143.90, 137.38, 132.71, 130.77, 128.97, 128.90, 128.27, 127.90, 127.62, 125.15, 120.65, 116.14, 116.08, 54.03, 47.82, 45.73, 42.79.

[1157] HRMS (APCI): Calcd for C 26 H 26 N4O2 [M + H] + = 427.2129; Found [M + H] + = 427.2134.

[1158] Preparation Example 155: 1-(4-(6-Chlorofuro[3,2-b]pyridin-3-yl)pyridin-2-yl)ethan-1-one

[1159]

[1160] Using 300 mg (1.291 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 415 mg (1.678 mmol) of 1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)ethan-1-one, the compound was prepared by General Procedure A; the reaction time was 5 hours. The reaction mixture was passed through The mixture of 535 and SiO2 (1:1, 8 g) was filtered while hot, and the filtrate was concentrated under vacuum. Flash column chromatography (DCM / MeOH, gradient from 99:1 to 49:1) gave the product as an off-white solid (27 mg, 8% yield).

[1161] 1 1H NMR (500 MHz, CDCl3) δ 8.83 (d, J = 5.0 Hz, 1H), 8.69 (d, J = 2.1 Hz, 1H), 8.57 (d, J = 1.7 Hz, 1H), 8.47 (dd, J = 1.7, 5.1 Hz, 1H), 8.40 (s, 1H), 7.91 (d, J = 2.1 Hz, 1H), 2.81 (s, 3H).

[1162] 13 13C NMR (126 MHz, CDCl3) δ 199.99, 153.95, 149.74, 148.58, 147.59, 145.87, 143.45, 139.00, 128.38, 124.71, 119.14, 119.11, 118.74, 25.93.

[1163] Preparation Example 156: 1-(4-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)pyridin-2-yl)ethan-1-one

[1164]

[1165] Using 25 mg (0.092 mmol) of 1-(4-(6-chlorofuro[3,2-b]pyridin-3-yl)pyridin-2-yl)ethan-1-one (Preparation Example 155) and 36 mg (0.119 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 5 h. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g) while hot, and the filtrate was concentrated under vacuum. Flash column chromatography (DCM / MeOH, gradient from 1:0 to 19:1) gave the product as an off-white solid (14 mg, 36% yield).

[1166] 11H NMR (500 MHz, DMSO-d6) δ 9.22 (s, 1H), 9.02 (d, J = 1.9 Hz, 1H), 8.89 (dd, J = 0.8, 1.8 Hz, 1H), 8.83 (dd, J = 0.8, 5.1 Hz, 1H), 8.49 (dd, J = 1.7, 5.1 Hz, 1H), 8.39 (d, J = 1.9 Hz, 1H), 7.69 - 7.74 (m, 2H), 7.05 - 7.11 (m, 2H), 3.21 - 3.26 (m, 4H), 2.70 (s, 3H), 2.46 - 2.50 (m, 4H), 2.24 (s, 3H).

[1167] 13 13C NMR (126 MHz, DMSO-d6) δ 200.04, 154.24, 151.36, 150.22, 150.15, 149.61, 145.31, 143.10, 139.92, 133.35, 128.31, 127.08, 124.48, 118.50, 117.90, 116.42, 116.04, 54.97, 48.12, 46.26, 26.28.

[1168] HRMS (APCI): Calcd for C 25 H 24 N4O2 [M + H] + = 413.1972; Found [M + H] + = 413.1973.

[1169] Preparation Example 157: 3-([1,1'-Biphenyl]-3-yl)-6-chlorofuro[3,2-b]pyridine

[1170]

[1171] Using 300 mg (1.290 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 332 mg (1.678 mmol) of 3-phenylphenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 3.5 h. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 93:7) gave the product as an off-white solid (400 mg, 100% yield).

[1172] 11H NMR (500 MHz, CDCl3) δ 8.56 (d, J = 2.1 Hz, 1H), 8.17 (dd, J = 1.8, 1.8 Hz, 1H), 8.09 (s, 1H), 7.95 (ddd, J = 1.5, 1.5, 7.5 Hz, 1H), 7.77 (d, J = 2.1 Hz, 1H), 7.57 - 7.62 (m, 2H), 7.53 (ddd, J = 1.5, 1.5, 7.8 Hz, 1H), 7.48 (dd, J = 7.6, 7.6 Hz, 1H), 7.37 - 7.43 (m, 2H), 7.28 - 7.33 (m, 1H).

[1173] 13 13C NMR (126 MHz, CDCl3) δ 147.40, 144.59, 144.26, 143.39, 140.93, 140.02, 129.30, 128.32, 127.83, 126.62, 126.46, 126.29, 125.89, 125.06, 124.98, 120.88, 117.70.

[1174] Preparation Example 158: 3-([1,1'-Biphenyl]-3-yl)-6-(4-(4-methylpiperazin-1-yl)phenyl)furo [3,2-b]pyridine

[1175]

[1176] Using 135 mg (0.442 mmol) of 3-([1,1'-biphenyl]-3-yl)-6-chlorofuro[3,2-b]pyridine (Preparation Example 157) and 174 mg (0.575 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours. The reaction mixture was hot filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 99:1 to 19:1) gave the product as an off-white solid (55 mg, 28% yield).

[1177] 11H NMR (500 MHz, CDCl3) δ 8.92 (d, J = 1.9 Hz, 1H), 8.31 (dd, J = 1.8, 1.8 Hz, 1H), 8.19 (s, 1H), 8.13 (ddd, J = 1.6, 1.6, 7.3 Hz, 1H), 7.95 (d, J = 1.8 Hz, 1H), 7.69 - 7.75 (m, 2H), 7.57 - 7.65 (m, 4H), 7.47 - 7.53 (m, 2H), 7.40 (ddd, J = 1.3, 7.1, 7.4 Hz, 1H), 7.04 - 7.11 (m, 2H), 3.30 - 3.41 (m, 4H), 2.61 - 2.74 (m, 4H), 2.43 (s, 3H).

[1178] 13 13C NMR (126 MHz, DMSO-d6) δ 151.17, 149.414, 147.50, 144.85, 143.91, 141.22, 140.67, 132.79, 131.61, 129.80, 129.44, 128.25, 128.09, 127.46, 127.34, 126.45, 126.13, 125.37, 120.49, 116.11, 116.07, 54.86, 48.03, 46.07.

[1179] HRMS (APCI): Calcd for C 30 H 27 N3O [M + H] + = 446.2227; Found [M + H] + = 446.2230.

[1180] Preparation Example 159: 3-([1,1'-Biphenyl]-2-yl)-6-chlorofuro[3,2-b]pyridine

[1181]

[1182] Using 150 mg (0.645 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 166 mg (0.839 mmol) of 2-phenylphenylboronic acid, the compound was prepared by General Procedure A; the mixture was stirred for 3.5 h. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 93:7) gave the product as a white solid (190 mg, 97% yield).

[1183] 11H NMR (500 MHz, CDCl3) δ 8.39 (d, J = 2.0 Hz, 1H), 7.89 (ddd, J = 7.6, 1.0, 1.0 Hz, 1H), 7.53 (d, J = 2.1 Hz, 1H), 7.37 - 7.30 (m, 1H), 7.29 - 7.26 (m, 2H), 7.13 - 7.10 (m, 5H), 6.98 (s, 1H).

[1184] 13 13C NMR (126 MHz, CDCl3) δ 147.83, 147.43, 145.16, 145.11, 141.74, 141.65, 130.60, 129.38, 128.27, 128.11, 127.74, 127.68, 127.46, 127.32, 127.14, 120.88, 118.51.

[1185] Preparation Example 160: tert-Butyl 4-(4-(3-([1,1'-Biphenyl]-2-yl)furo[3,2-b]pyridin-6-yl) phenyl)piperazine-1-carboxylate

[1186]

[1187] Using 197 mg (0.644 mmol) of 3 - ([1,1'-biphenyl]-2-yl)-6-chlorofuro[3,2-b]pyridine (Preparation Example 159) and 325 mg (0.837 mmol) of tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate, the compound was prepared by General Procedure B. The reaction time was 2.5 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated. Column chromatography (cyclohexane / EtOAc, gradient from 9:1 to 4:1) gave a pale yellow solid product (240 mg, 70% yield).

[1188] NMR (500 MHz, CDCl3) δ 8.85 (d, J = 1.9 Hz, 1H), 8.14 (ddd, J = 1.0, 1.0, 7.8 Hz, 1H), 7.87 (d, J = 1.9 Hz, 1H), 7.56 - 7.61 (m, 2H), 7.54 (ddd, J = 3.5, 5.4, 7.7 Hz, 1H), 7.44 - 7.48 (m, 2H), 7.29 - 7.34 (m, 5H), 7.14 (s, 1H), 7.08 (d, J = 8.3 Hz, 2H), 3.60 - 3.70 (m, 4H), 3.20 - 3.30 (m, 4H), 1.52 (s, 9H).

[1189] 1313C NMR (126 MHz, CDCl3) δ 154.71, 148.31, 147.30, 144.83, 141.87, 141.52, 132.67, 130.58, 130.53, 129.44, 128.20, 127.80, 127.74, 127.00, 120.55, 116.83, 80.03, 60.36, 49.09, 28.44。

[1190] Preparation Example 161: 3-([1,1'-Biphenyl]-2-yl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b] pyridine

[1191]

[1192] Using 190 mg (0.357 mmol) of tert-butyl 4-(4-(3-([1,1'-biphenyl]-2-yl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 160), the compound was prepared by General Procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 1:1) gave the compound as a pale yellow solid (134 mg, 87% yield).

[1193] 1 1H NMR (500 MHz, CD3OD) δ 8.65 (d, J = 1.9 Hz, 1H), 8.07 (d, J = 1.9 Hz, 1H), 7.79 - 7.84 (m, 1H), 7.59 - 7.64 (m, 2H), 7.46 - 7.54 (m, 4H), 7.20 - 7.29 (m, 5H), 7.10 - 7.15 (m, 2H), 3.29 - 3.32 (m, 4H), 3.10 - 3.14 (m, 4H).

[1194] 13 13C NMR (126 MHz, CD3OD) δ 151.24, 148.64, 147.48, 144.50, 143.68, 142.27, 141.58, 133.19, 130.79, 130.02, 128.97, 128.77, 127.97, 127.92, 127.64, 127.12, 126.62, 121.24, 116.38, 116.00, 48.36, 44.63.

[1195] HRMS (APCI): Calcd for C 29 H 25 N3O [M + H] + = 432.2070; Found [M + H] + = 432.2071.

[1196] Preparation Example 162: 6-Chloro-3-(3-(cyclobutylthio)phenyl)furo[3,2-b]pyridine

[1197]

[1198] Using 150 mg (0.645 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 175 mg (0.839 mmol) of (3-(cyclobutylthio)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2.5 hours. The reaction mixture was filtered hot through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 19:1) gave the product as a pale yellow viscous oil (202 mg, 99% yield).

[1199] 1 1H NMR (500 MHz, CDCl3) δ 8.54 (d, J = 2.0 Hz, 1H), 8.03 (s, 1H), 7.88 (dd, J = 1.7, 1.7 Hz, 1H), 7.72 - 7.79 (m, 2H), 7.23 - 7.33 (m, 1H), 7.12 - 7.20 (m, 1H), 3.82 - 3.95 (m, 1H), 2.37 - 2.51 (m, 2H), 1.87 - 2.13 (m, 4H).

[1200] 13 13C NMR (126 MHz, CDCl3) δ 148.37, 145.59, 145.24, 144.25, 137.91, 130.46, 129.21, 128.30, 127.64, 127.30, 124.31, 121.41, 118.69, 40.26, 30.69, 18.81.

[1201] HRMS (APCI): Calcd for C 17 H 14 ClNOS [M + H] + = 316.0557; Found [M + H] + = 316.0557.

[1202] Preparation Example 163: tert-Butyl 4-(4-(3-(3-(cyclobutylthio)phenyl)furo[3,2-b]pyridin-6- yl)phenyl)piperazine-1-carboxylate

[1203]

[1204] Using 204 mg (0.646 mmol) of 6-chloro-3-(3-(cyclobutylthio)phenyl)furo[3,2-b]pyridine (Preparation Example 162) and 326 mg (0.840 mmol) of tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate, the compound was prepared by General Procedure B. The reaction time was 3 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient 9:10 to 83:17) gave the product as a yellow solid (230 mg, 66% yield).

[1205] 1 1H NMR (500 MHz, CDCl3) δ 8.79 (d, J = 2.0 Hz, 1H), 8.02 (s, 1H), 7.93 (dd, J = 1.8, 1.8 Hz, 1H), 7.81 - 7.85 (m, 2H), 7.49 (d, J = 8.9 Hz, 2H), 7.30 (dd, J = 7.7, 7.7 Hz, 1H), 7.16 (d, J = 6 - 6 Hz, 1H), 6.96 (d, J = 8.9 Hz, 2H), 3.91 (p, J = 7.8 Hz, 1H), 3.50 - 3.57 (m, 4H), 3.11 - 3.18 (m, 4H), 2.41 - 2.49 (m, 2H), 1.87 - 2.13 (m, 4H), 1.42 (s, 9H).

[1206] 13 13C NMR (126 MHz, CDCl3) δ 154.72, 150.95, 149.33, 145.01, 144.94, 144.23, 137.70, 132.92, 131.15, 129.40, 129.19, 128.20, 128.13, 127.38, 124.45, 121.33, 116.73, 115.89, 80.00, 48.97, 43.43, 40.43, 30.82, 28.475, 18.80.

[1207] Preparation Example 164: 3-(3-(cyclobutylthio)phenyl)-6-(4-(piperazin-1-yl)phenyl]furo[3,2- b]pyridine

[1208]

[1209] Using 190 mg (0.351 mmol) of tert-butyl 4-(4-(3-(3-(cyclobutylthio)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 163), the compound was prepared by the general procedure C; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 0:1) gave the compound as a pale yellow solid (70 mg, 45% yield).

[1210] 1 H NMR (500 MHz, CD3OD) δ 8.86 (d, J = 1.9 Hz, 1H), 8.44 (s, 1H), 8.14 (d, J = 1.9 Hz, 1H), 8.09 (dd, J = 1.8, 1.8 Hz, 1H), 7.85 (ddd, J = 1.4, 1.4, 7.7 Hz, 1H), 7.66 - 7.70 (m, 2H), 7.40 (dd, J = 7.7, 7.5 Hz, 1H), 7.27 (ddd, J = 1.1, 1.9, 7.9 Hz, 1H), 7.13 - 7.18 (m, 2H), 4.07 (p, J = 7.8 Hz, 1H), 3.33 - 3.36 (m, 4H), 3.13 - 3.18 (m, 4H), 2.52 - 2.62 (m, 2H), 2.03 - 2.18 (m, 4H).

[1211] 13 C NMR (126 MHz, CD3OD) δ 151.55, 149.37, 147.48, 144.80, 143.72, 137.59, 132.78, 131.72, 129.77, 128.22, 127.45, 127.41, 126.36, 124.12, 119.96, 116.06, 49.05, 48.65, 45.36, 30.56, 18.81.

[1212] HRMS (APCI): Calcd for C 27 H 27 N3OS [M + H] + = 442.1948; Found [M + H] + = 442.1951.

[1213] Preparation Example 165: Methyl 3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzoate

[1214]

[1215] Using 120 mg (0.516 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 121 mg (0.671 mmol) of 3-(methoxycarbonyl)phenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 4 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 19:1) gave the product as an off-white solid (82 mg, 55% yield).

[1216] 1 1H NMR (500 MHz, CDCl3) δ 8.57 (d, J = 2.0 Hz, 1H), 8.53 (dd, J = 1.8, 1.8 Hz, 1H), 8.25 (ddd, J = 1.4, 1.4, 7.8 Hz, 1H), 8.12 (s, 1H), 7.97 (ddd, J = 1.4, 1.4, 7.8 Hz, 1H), 7.77 (d, J = 2.1 Hz, 1H), 7.50 (dd, J = 7.8, 7.8 Hz, 1H), 3.89 (s, 3H).

[1217] 13 13C NMR (126 MHz, DMSO-d6) δ 166.61, 149.04, 148.50, 145.46, 144.12, 131.66, 130.92, 130.77, 129.76, 128.95, 127.67, 127.42, 120.06, 119.70, 52.79.

[1218] Preparation Example 166: tert-Butyl 4-(4-(3-(3-(butoxycarbonyl)phenyl)furo[3,2-b]pyridin-6-yl) phenyl)piperazine-1-carboxylate

[1219]

[1220] Using 80 mg (0.278 mmol) of methyl 3-(6-chlorofuro[3,2-b]pyridin-3-yl)benzoate (Preparation Example 165) and 140 mg (0.361 mmol) of tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate, the compound was prepared by General Procedure B. The reaction time was 4 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 11:0 to 0:1, then DCM / MeOH, gradient from 4:1 to 7:3) gave the product as a pale beige solid (56 mg, 37%).

[1221] 1 1H NMR (500 MHz, CDCl3) δ 8.92 (d, J = 1.9 Hz, 1H), 8.66 (dd, J = 1.7, 1.7 Hz, 1H), 8.47 (ddd, J = 1.5, 1.5, 7.8 Hz, 1H), 8.22 (s, 1H), 8.06 (ddd, J = 1.5, 1.5, 7.8 Hz, 1H), 7.97 (d, J = 1.9 Hz, 1H), 7.58 - 7.64 (m, 3H), 7.08 - 7.15 (m, 2H), 4.40 (t, J = 6.6 Hz, 2H), 3.61 - 3.71 (m, 4H), 3.22 - 3.31 (m, 4H), 1.77 - 1.87 (m, 2H), 1.52 (s, 9H), 1.49 - 1.61 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H).

[1222] 13 13C NMR (126 MHz, CDCl3) δ 166.61, 154.71, 149.31, 145.24, 145.08, 144.10, 133.05, 131.62, 131.13, 130.87, 128.98, 128.68, 128.27, 127.93, 121.02, 116.90, 116.09, 80.06, 64.99, 49.14, 43.4, 30.83, 28.45, 19.30, 13.79.

[1223] Preparation Example 167: Butyl 3-(6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzo ate

[1224]

[1225] At 25 °C, to a heterogeneous mixture of 23 mg (0.041 mmol) of tert-butyl 4-(4-(3-(3-(butoxycarbonyl)phenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 166) in 5.0 mL of anhydrous 1,4-dioxane was added 0.73 mL of a 1,4-dioxane solution of 4 M HCl. The mixture was stirred at 25 °C for 5 h. The progress of the reaction was monitored by TLC. The reaction mixture was concentrated in vacuo, 500 mg (5.952 mmol) of solid sodium bicarbonate was added to the residue, and the mixture was stirred in DCM / MeOH 5:1 (12 mL) for 2.5 h. The mixture was passed through Filtered through a pad of 535 and SiO2 (1:1; 8 g), and the pad was washed with 50 mL of a 5:1 mixture of DCM / MeOH. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography (DCM / MeOH, gradient 9:1 to 4:1) to give a pale yellow solid product (12 mg, 65%).

[1226] 1 1H NMR (500 MHz, CDCl3) δ 8.91 (d, J = 2.0 Hz, 1H), 8.66 (dd, J = 1.8, 1.8 Hz, 1H), 8.47 (ddd, J = 7.8, 1.5, 1.5 Hz, 1H), 8.22 (s, 1H), 8.06 (ddd, J = 7.8, 1.5, 1.5 Hz, 1H), 7.96 (d, J = 1.9 Hz, 1H), 7.65 - 7.57 (m, 3H), 7.12 - 7.05 (m, 2H), 4.40 (t, J = 6.6 Hz, 2H), 3.50 - 3.45 (m, 4H), 3.34 - 3.28 (m, 4H), 1.87 - 1.77 (m, 2H), 1.60 - 1.49 (m, 2H), 1.03 (t, J = 7.4 Hz, 3H).

[1227] 13 13C NMR (126 MHz, CDCl3) δ 166.61, 150.23, 149.26, 145.31, 145.14, 144.32, 132.86, 131.62, 131.15, 130.87, 130.45, 128.98, 128.72, 128.38, 127.93, 121.04, 117.25, 116.03, 65.00, 47.63, 44.16, 30.83, 19.30, 13.78.

[1228] Preparation Example 168: 6-Chloro-3-(3-fluorophenyl)furo[3,2-b]pyridine

[1229]

[1230] The compound was prepared by General Procedure A using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 78 mg (0.559 mmol) of (3-fluorophenyl)boronic acid; the reaction time was 2 hours; flash chromatography (cyclohexane) gave a white solid compound (98 mg, 92% yield).

[1231] 11H NMR (500 MHz, methanol-d4) δ 8.61 (d, J = 2.1 Hz, 1H), 8.53 (s, 1H), 8.08 (d, J = 2.0 Hz, 1H), 7.96 (ddd, J = 10.5, 2.7, 1.6 Hz, 1H), 7.89 (ddd, J = 7.8, 1.6, 0.9 Hz, 1H), 7.46 (td, J = 8.0, 6.1 Hz, 1H), 7.09 (tdd, J = 8.5, 2.7, 0.9 Hz, 1H).

[1232] 13 13C NMR (126 MHz, MeOD) δ 165.45, 163.51, 150.01, 148.74, 146.12, 145.27, 133.65, 133.58, 131.53, 131.46, 129.75, 128.99, 128.22, 123.78, 123.75, 121.53, 121.51, 120.23, 115.60, 115.42, 114.94, 114.75.

[1233] HRMS (APCI): Calcd for C 13 H7ClFNO [M + H] + = 248.0273; Found [M + H] + = 248.0274.

[1234] FTIR (neat), cm -1 : 3106, 3085, 3073, 1617, 1589, 1488, 1436, 1386, 1352, 1266, 1232, 1185, 1128, 1100, 1076, 998, 919, 878, 851, 815, 779, 686, 600, 514, 453, 438.

[1235] Preparation Example 169: tert-Butyl 4-(4-(3-(3-fluorophenyl)furo[3,2-b]pyridin-6-yl)phenyl)pip erazine-1-carboxylate

[1236]

[1237] Using 80 mg (0.323 mmol) of 6-chloro-3-(3-fluorophenyl)furo[3,2-b]pyridine (Preparation Example 168) and 163 mg (0.420 mmol) of 4-(4-tert-butoxycarbonylpiperazinyl)phenylboronic acid pinacol ester, the compound was prepared by the general procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 7:3) gave a pale yellow solid compound (98 mg, 64% yield).

[1238] 1 1H NMR (500 MHz, chloroform-d) δ 8.88 (d, J = 1.9 Hz, 1H), 8.12 (s, 1H), 7.93 - 7.84 (m, 3H), 7.59 - 7.54 (m, 2H), 7.44 (td, J = 7.9, 6.0 Hz, 1H), 7.09 - 7.00 (m, 3H), 3.68 - 3.57 (m, 4H), 3.28 - 3.19 (m, 4H), 1.50 (s, 10H).

[1239] 13 13C NMR (126 MHz, CDCl3) δ 164.26, 162.31, 154.86, 151.12, 149.44, 145.28, 145.21, 144.08, 133.25, 132.82, 132.75, 130.47, 130.40, 129.37, 128.33, 122.75, 122.72, 120.92, 120.89, 116.85, 116.12, 114.75, 114.58, 114.25, 114.07, 80.14, 77.16, 49.06, 43.42, 28.58.

[1240] HRMS (APCI): Calculated for C 28 H 28 FN3O3 [M + H] + = 474.2187; Found [M + H] + = 474.2187.

[1241] FTIR (neat), cm -1 2977, 2921, 2825, 1689, 1607, 1524, 1480, 1448, 1425, 1401, 1379, 1365, 1259, 1233, 1215, 1160, 1131, 1115, 1088, 1046, 999, 904, 876, 845, 817, 786, 689, 539, 519.

[1242] Preparation Example 170: 3-(3-Fluorophenyl)-6-(4-(piperazin-1-yl)phenyl)furo[3,2-b]pyridine

[1243]

[1244] Using 90 mg (0.190 mmol) of tert-butyl 4-(4-(3-(3-fluorophenyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 169), the compound was prepared by the general procedure C; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 4:1) gave the compound as a pale yellow solid (59 mg, 83% yield).

[1245] 1 H NMR (300 MHz, chloroform-d) δ 8.95 (d, J = 1.9 Hz, 1H), 8.93 (s, 1H), 8.33 (d, J = 1.9 Hz, 1H), 8.22 - 8.06 (m, 2H), 7.74 - 7.67 (m, 2H), 7.61 - 7.48 (m, 1H), 7.20 (td, J = 8.6, 2.7 Hz, 1H), 7.09 - 7.03 (m, 2H), 3.25 - 3.14 (m, 4H), 2.94 (dd, J = 6.6, 3.5 Hz, 4H).

[1246] 13 C NMR (126 MHz, DMSO) δ 163.33, 161.40, 151.22, 148.89, 147.38, 144.37, 142.94, 132.83, 132.76, 132.45, 130.67, 130.60, 127.71, 126.73, 122.45, 122.43, 118.88, 118.86, 115.66, 115.47, 114.26, 114.10, 113.08, 112.89, 48.52, 45.19, 39.52.

[1247] HRMS (APCI): Calcd for C 23 H 20 FN3O [M + H] + = 374.1663; Found [M + H] + = 374.1664.

[1248] FTIR (neat), cm -1 : 2943, 2846, 2822, 1604, 1587, 1570, 1523, 1481, 1449, 1380, 1335, 1260, 1242, 1216, 1146, 1116, 1097, 911, 891, 847, 821, 788, 689, 664, 544, 516.

[1249] Preparation Example 171: 6-(4-(2-(Piperidin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)furo[3, 2-b]pyridine

[1250]

[1251] Using 140 mg (0.607 mmol) of 6-chloro-3-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 21) and 261 mg (0.789 mmol) of 1-(2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethyl)piperidine, the compound was prepared by General Procedure B; the reaction time was 75 minutes; flash chromatography (column: 6 g of C 18 coated silica gel; eluent: MeOH solution of H2O / 7M NH3, gradient 2:1 to 1:49), and then by preparative TLC (DCM / MeOH solution of 7M NH3, 16:1), to obtain the white solid compound (133 mg, 60% yield).

[1252] 1 1H NMR (500 MHz, chloroform-d) δ 8.89 (d, J = 1.9 Hz, 1H), 8.77 - 8.68 (m, 2H), 8.27 (s, 1H), 8.10 - 8.03 (m, 2H), 7.95 (d, J = 1.8 Hz, 1H), 7.62 - 7.54 (m, 2H), 7.10 - 7.03 (m, 2H), 4.20 (t, J = 6.0 Hz, 2H), 2.85 (t, J = 6.0 Hz, 2H), 2.68 - 2.49 (m, 4H), 1.65 (p, J = 5.7 Hz, 4H), 1.55 - 1.42 (m, 2H).

[1253] 13 13C NMR (126 MHz, chloroform-d) δ 159.21, 150.53, 149.56, 146.57, 145.65, 143.88, 138.41, 133.66, 130.43, 128.73, 121.41, 119.63, 116.63, 115.56, 66.24, 57.98, 55.21, 25.97, 24.25.

[1254] FTIR (neat), cm -1 : 3040, 2932, 2783, 1603, 1520, 1479, 1262, 1245, 1204, 1127, 1097, 1033, 826, 732, 670, 537, 518.

[1255] Preparation Example 172: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-phenylfuro[3,2-b]pyridine

[1256]

[1257] Using 100 mg (0.435 mmol) of 6-chloro-3-phenylfuro[3,2-b]pyridine (Preparation Example 100) and 158 mg (0.523 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a white solid (153 mg, 95% yield).

[1258] 1 H NMR (500 MHz, chloroform-d) δ 8.89 (d, J = 1.9 Hz, 1H), 8.11 (s, 1H), 8.11 - 8.06 (m, 2H), 7.92 (d, J = 1.8 Hz, 1H), 7.60 - 7.53 (m, 2H), 7.49 (dd, J = 8.4, 7.1 Hz, 2H), 7.38 (d, J = 7.4 Hz, 1H), 7.09 - 7.02 (m, 2H), 3.34 (t, J = 5.0 Hz, 4H), 2.66 (bs, 4H), 2.41 (s, 3H).

[1259] 13 C NMR (126 MHz, CDCl3) δ 151.11, 149.47, 145.12, 144.89, 144.42, 133.16, 130.70, 129.01, 128.29, 127.86, 127.28, 121.96, 116.39, 116.03, 55.22, 55.13, 53.54, 49.13, 48.76, 46.22.

[1260] HRMS (APCI): Calcd for C 24 H 23 N3O [M+H] + = 370.1914; Found [M+H] + = 370.1911.

[1261] FTIR (neat), cm -1 : 2940, 2843, 2800, 1604, 1525, 1478, 1445, 1381, 1293, 1245, 1201, 1159, 1140, 1122, 1098, 967, 918, 820, 789, 779, 752, 691, 671, 530, 504.

[1262] Preparation Example 173: N-Methyl-N-(3-(6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]py ridin-3-yl)phenyl)acetamide

[1263]

[1264] TEA (0.052 mL, 0.370 mmol) and acetic anhydride (0.074 mL, 0.740 mmol) were added to a solution of 59 mg (0.148 mmol) of N-methyl-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)aniline (Preparation Example 110) in DCM (2 mL), and the mixture was stirred at 25 °C for 3 hours. The volatiles were evaporated in vacuo, and the residue was purified by flash chromatography (DCM / MeOH, gradient 1:0 to 4:1). A pale gray solid product (65 mg, 100% yield) was obtained.

[1265] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.9 Hz, 1H), 8.15 (s, 1H), 8.09 - 8.02 (m, 2H), 7.93 (d, J = 1.9 Hz, 1H), 7.60 - 7.55 (m, 2H), 7.53 (t, J = 7.8 Hz, 1H), 7.19 (bd, J = 7.7 Hz, 1H), 7.09 - 7.02 (m, 2H), 3.35 (s, 3H), 3.33 - 3.28 (m, 4H), 2.65 - 2.58 (m, 4H), 2.38 (s, 3H), 1.98 (s, 3H).

[1266] 13 13C NMR (126 MHz, CDCl3) δ 170.82, 151.27, 149.54, 145.33, 145.12, 143.97, 133.52, 132.59, 130.32, 130.28, 128.72, 128.30, 126.27, 126.25, 125.97, 120.86, 116.35, 116.11, 55.18, 48.80, 46.31, 37.39, 22.75.

[1267] HRMS (APCI): Calcd for C 27 H 28 N4O2 [M + H] + = 441.2285; Found [M + H] + = 441.2286.

[1268] Preparation Example 174: 6-Chloro-3-(3-(methylsulfonyl)phenyl)furo[3,2-b]pyridine

[1269]

[1270] Compound was prepared by General Procedure A using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 103 mg (0.515 mmol) of (3-(methylsulfonyl)phenyl)boronic acid; the reaction time was 2 h; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 3:1) gave the compound as a white solid (96 mg, 73% yield).

[1271] 1 H NMR (500 MHz, CDCl3) δ 8.64 (d, J = 2.0 Hz, 1H), 8.58 (t, J = 1.7 Hz, 1H), 8.48 - 8.43 (m, 1H), 8.24 (s, 1H), 7.96 - 7.92 (m, 1H), 7.87 (d, J = 2.0 Hz, 1H), 7.70 (t, J = 7.8 Hz, 1H), 3.13 (s, 3H).

[1272] 13 C NMR (126 MHz, CDCl3) δ 148.59, 146.38, 145.76, 143.84, 141.49, 132.30, 131.78, 130.14, 128.29, 126.63, 125.74, 120.30, 119.15, 44.67.

[1273] HRMS (APCI): Calcd for C 14 H 10 ClNO3S [M + H] + = 308.0143; Found [M + H] + = 308.0147.

[1274] Preparation Example 175: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(3-(methylsulfonyl)phenyl)fur o[3,2-b]pyridine

[1275]

[1276] Compound was prepared by General Procedure B using 59 mg (0.192 mmol) of 6-chloro-3-(3-(methylsulfonyl)phenyl)furo[3,2-b]pyridine (Preparation Example 174) and 79 mg (0.261 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine; the reaction time was 2 h; flash chromatography (DCM / MeOH, gradient 1:0 to 93:7) gave the compound as a white solid (54 mg, 63% yield).

[1277] 1H NMR (500 MHz, CDCl3) δ 8.88 (d, J = 1.9 Hz, 1H), 8.62 (t, J = 1.7 Hz, 1H), 8.55 - 8.51 (m, 1H), 8.22 (s, 1H), 7.96 - 7.89 (m, 2H), 7.69 (t, J = 7.8 Hz, 1H), 7.59 - 7.54 (m, 2H), 7.07 - 7.01 (m, 2H), 3.35 - 3.27 (m, 4H), 3.13 (s, 3H), 2.65 - 2.58 (m, 4H), 2.37 (s, 3H).

[1278] 13 13C NMR (126 MHz, CDCl3) δ 151.26, 149.51, 145.59, 145.42, 143.61, 141.34, 133.68, 132.49, 132.31, 130.04, 128.51, 128.26, 126.25, 125.64, 120.17, 116.29, 116.15, 55.13, 48.72, 46.28, 44.66.

[1279] HRMS (APCI): Calcd for C 25 H 25 N3O3S [M + H] + = 448.1689; Found [M + H] + = 448.1692.

[1280] Preparation Example 176: 4,4,5,5-Tetramethyl-2-(3-(perfluoroethyl)phenyl)-1,3,2-dioxaborolane

[1281]

[1282] Pd(dppf)Cl2 (39.9 mg, 0.055 mmol) was added to a degassed solution of 1-bromo-3-(perfluoroethyl)benzene (300 mg, 1.092 mmol), bis(pinacolato)diboron (306 mg, 1.200 mmol) and potassium acetate (321 mg, 3.276 mmol) in 6.0 mL of anhydrous 1,4-dioxane. The mixture was heated to 85 °C for 6.5 h. The mixture was cooled to 25 °C and stirred for an additional 86 h. The reaction was monitored by TLC. The mixture was filtered through a 535 pad, and the filtrate was washed with brine (3 × 25 mL). The combined aqueous layers were extracted with 25 mL of EtOAc. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1). A colorless liquid product (271 mg, 67% yield) was obtained.

[1283] 1 1H NMR (500 MHz, CDCl3) δ 7.97 - 7.94 (m, 1H), 7.94 - 7.89 (m, 1H), 7.62 - 7.58 (m, 1H), 7.45 - 7.40 (m, 1H), 1.29 (s, 12H).

[1284] 13 13C NMR (126 MHz, CDCl3) δ 138.17, 132.53, 132.48, 132.43, 129.04, 128.98, 128.93, 128.20, 128.00, 84.27, 24.86. Perfluoroethyl carbons in the range of 110 - 120 ppm were not reported.

[1285] Preparation Example 177: 6-Chloro-3-(3-(perfluoroethyl)phenyl)furo[3,2-b]pyridine

[1286]

[1287] Using 120 mg (0.516 mmol) of 3 - bromo - 6 - chlorofuro[3,2 - b]pyridine (Preparation Example 5) and 216 mg (0.671 mmol) of 4,4,5,5 - tetramethyl - 2 - (3 - (perfluoroethyl)phenyl)-1,3,2 - dioxaborolane (Preparation Example 176), the compound was prepared by General Procedure A; the reaction time was 2.5 hours. The reaction mixture was hot - filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 16:1) gave the white solid product (175 mg, 98% yield).

[1288] 1 1H NMR (500 MHz, CDCl3) δ 8.57 (d, J = 2.1 Hz, 1H), 8.25 (d, J = 7.2 Hz, 1H), 8.17 (s, 1H), 8.11 (s, 1H), 7.78 (d, J = 2.0 Hz, 1H), 7.58 - 7.51 (m, 2H).

[1289] 1313C NMR (126 MHz, CDCl3) δ 148.42, 145.52, 143.89, 130.53, 129.66, 129.47, 129.35, 129.28, 125.86, 125.81, 125.77, 124.92, 124.87, 124.82, 120.67, 120.59, 120.27, 118.87, 118.00, 117.69, 115.73, 115.54, 115.23, 113.52, 113.21, 111.50, 111.20。

[1290] HRMS (APCI): Calcd for C 15 H7ClF5NO [M + H] + = 348.0209; Found [M + H] + = 348.0208。

[1291] Preparation Example 178: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(3-(perfluoroethyl)phenyl)furo [3,2-b]pyridine

[1292]

[1293] Using 100 mg (0.288 mmol) of 6-chloro-3-(3-(perfluoroethyl)phenyl)furo[3,2-b]pyridine (Preparation Example 177) and 113 mg (0.374 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 1.5 h; the reaction mixture was hot filtered through a pad of 535 and SiO2 (1:1, 8 g), and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 1:0 to 19:1) gave the product as an off-white solid (75 mg, 53% yield).

[1294] 1 1H NMR (500 MHz, CDCl3) δ 8.92 (d, J = 2.0 Hz, 1H), 8.44 (d, J = 7.6 Hz, 1H), 8.30 (s, 1H), 8.20 (s, 1H), 7.96 (d, J = 1.8 Hz, 1H), 7.66 (dd, J = 7.5, 7.5 Hz, 1H), 7.64 - 7.57 (m, 3H), 7.08 (d, J = 8.9 Hz, 2H), 3.36 - 3.31 (m, 4H), 2.66 - 2.61 (m, J = 5.1 Hz, 4H), 2.40 (s, 3H).

[1295] 1313C NMR (126 MHz, CDCl3) δ 151.11, 149.37, 145.27, 145.13, 143.74, 133.41, 131.55, 130.59, 129.55, 129.36, 129.30, 129.17, 128.55, 128.21, 125.48, 124.83, 120.62, 116.17, 115.97, 55.03, 48.64, 46.16。

[1296] HRMS (APCI): Calculated for C 26 H 22 F5N3O [M+H] + = 488.1756; Found [M+H] + = 488.1753。

[1297] Preparation Example 179: 6-Benzyl-3-phenylfuro[3,2-b]pyridine

[1298]

[1299] Using 41 mg (0.178 mmol) of 6-chloro-3-phenylfuro[3,2-b]pyridine (Preparation Example 100) and 50 mg (0.231 mmol) of 2-benzyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (cyclohexane / toluene, gradient from 1:0 to 1:1) gave the compound as a white solid (5.3 mg, 10% yield).

[1300] 1 1H NMR (500 MHz, CDCl3) δ 8.58 (d, J = 1.7 Hz, 1H), 8.08 - 8.02 (m, 3H), 7.57 (d, J = 1.7 Hz, 1H), 7.50 - 7.44 (m, 2H), 7.38 - 7.29 (m, 3H), 7.25 - 7.21 (m, 3H), 4.15 (s, 2H).

[1301] 13 13C NMR (126 MHz, CDCl3) δ 149.23, 147.09, 144.67, 144.49, 140.25, 132.98, 130.69, 129.04, 128.99, 128.91, 127.84, 127.26, 126.71, 121.87, 118.82, 39.32.

[1302] HRMS (APCI): Calculated for C 20 H 15 NO [M+H]+ = 286.1226; Measured value [M+H] + = 286.1227.

[1303] Preparation Example 180: 6-Chloro-3-(3-(methylsulfinyl)phenyl)furo[3,2-b]pyridine

[1304]

[1305] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 110 mg (0.559 mmol) of (3-(methylsulfinyl)phenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) gave a white solid compound (113 mg, 90% yield).

[1306] 1 H NMR (500 MHz, CDCl3) δ 8.60 (d, J = 2.0 Hz, 1H), 8.31 (br s, 1H), 8.24 (dt, J = 6.8, 1.8 Hz, 1H), 8.21 (s, 1H), 7.83 (d, J = 2.0 Hz, 1H), 7.66 - 7.59 (m, 2H), 2.80 (s, 3H).

[1307] 13 C NMR (126 MHz, CDCl3) δ 148.56, 146.81, 146.27, 145.60, 145.57, 144.04, 131.57, 130.02, 129.67, 128.09, 122.93, 121.95, 120.76, 119.04, 44.23.

[1308] HRMS (APCI): Calculated for C 14 H 10 ClNO2S [M+H] + = 292.0194; Measured value [M+H] + = 292.0192.

[1309] Preparation Example 181: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(3-(methylsulfinyl)phenyl)fur o[3,2-b]pyridine

[1310]

[1311] Using 109 mg (0.340 mmol) of 6-chloro-3-(3-(methylsulfinyl)phenyl)furo[3,2-b]pyridine (Preparation Example 180) and 134 mg (0.422 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 2 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 93:7) gave the compound as an off-white solid (93 mg, 63% yield).

[1312] 1 H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.8 Hz, 1H), 8.39 - 8.32 (m, 2H), 8.22 (s, 1H), 7.94 (d, J = 1.9 Hz, 1H), 7.69 - 7.61 (m, 2H), 7.59 - 7.55 (m, 2H), 7.08 - 7.03 (m, 2H), 3.35 - 3.27 (m, 4H), 2.81 (s, 3H), 2.65 - 2.57 (m, 4H), 2.38 (s, 3H).

[1313] 13 C NMR (126 MHz, CDCl3) δ 151.28, 149.54, 146.63, 145.52, 145.34, 143.88, 133.58, 132.30, 130.02, 129.75, 128.68, 128.30, 122.61, 121.98, 120.71, 116.34, 116.18, 55.17, 48.79, 46.31, 44.22.

[1314] HRMS (APCI): Calcd for C 25 H 25 N3O2S [M + H] + = 432.1740; Found [M + H] + = 432.1743.

[1315] Preparation Example 182: 1-(3-(6-Chlorofuro[3,2-b]pyridin-3-yl)phenyl)urea

[1316]

[1317] Using 191 mg (0.822 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 280 mg (1.069 mmol) of 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea, the compound was prepared by General Procedure A; the reaction time was 3 hours. The reaction mixture was passed through The mixture of 535 and SiO2 (1:1, 8 g) was subjected to hot filtration, and the filtrate was concentrated under vacuum. Flash chromatography (DCM / MeOH, gradient from 1:0 to 10:1) gave a light beige solid product (42 mg, 18% yield).

[1318] 1 1H NMR (500 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.68 (d, J = 2.0 Hz, 1H), 8.65 (s, 1H), 8.42 (d, J = 2.0 Hz, 1H), 8.08 (dd, J = 1.9, 1.9 Hz, 1H), 7.64 - 7.58 (m, 2H), 7.34 (dd, J = 7.9, 7.9 Hz, 1H), 5.86 (s, 2H).

[1319] 13 13C NMR (126 MHz, DMSO-d6) δ 156.44, 148.45, 148.22, 145.15, 144.40, 141.38, 130.44, 129.50, 127.21, 120.84, 120.09, 119.90, 117.96, 116.74.

[1320] HRMS (APCI): Calcd for C 14 H 10 ClN3O2 [M + H] + = 288.0534; Found [M + H] + = 288.0537.

[1321] Preparation Example 183: 1-(3-(6-Phenylfuro[3,2-b]pyridin-3-yl)phenyl)urea

[1322]

[1323] Using 60 mg (0.209 mmol) of 1-(3-(6-chlorofuro[3,2-b]pyridin-3-yl)phenyl)urea (Preparation Example 182) and 33 mg (0.271 mmol) of phenylboronic acid, the compound was prepared by General Procedure B. The reaction time was 24 hours. The reaction mixture was filtered through a pad of 535 and SiO2 (1:1, 8 g) under hot conditions, and the filtrate was concentrated under vacuum. Flash chromatography (DCM / MeOH, gradient from 1:0 to 19:1) gave a light brown solid product (36 mg, 53% yield).

[1324] 11H NMR (500 MHz, DMSO-d6) δ 8.96 (d, J = 1.8 Hz, 1H), 8.80 (s, 1H), 8.67 (s, 1H), 8.41 (d, J = 1.8 Hz, 1H), 8.16 (dd, J = 2.0, 2.0 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 9.2 Hz, 1H), 7.63 (d, J = 9.5 Hz, 1H), 7.55 (dd, J = 7.6, 7.6 Hz, 2H), 7.49 - 7.42 (m, 1H), 7.35 (dd, J = 7.9, 7.9 Hz, 1H), 5.87 (s, 2H).

[1325] 13 13C NMR (126 MHz, DMSO-d6) δ 156.47, 149.15, 147.61, 145.19, 144.85, 141.36, 137.70, 132.75, 130.98, 129.63, 129.47, 128.50, 127.83, 120.82, 120.08, 117.80, 117.35, 116.74.

[1326] HRMS (APCI): Calcd for C 20 H 15 N3O2 [M + H] + = 330.1237; Found [M + H] + = 330.1239.

[1327] Preparation Example 184: 5-Chloro-3-(cinnamyloxy)-2-iodopyridine

[1328]

[1329] Cinnamoyl bromide (463 mg, 2.349 mmol) was added to a mixture of 5-chloro-2-iodopyridin-3-ol (Preparation Example 1; 500 mg, 1.957 mmol) and K2CO3 (649 mg, 4.698 mmol) in acetone (16 mL). The resulting reaction mixture was stirred under reflux for 24 h. After cooling to ambient temperature, water (30 mL) was added and the mixture was extracted with EtOAc (3 × 40 mL). The organic portion was washed with brine (50 mL), dried over Na2SO4, filtered, and the solvent was evaporated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 20:1) gave the product as a pale yellow oil (712 mg, 98% yield).

[1330] 11H NMR (500 MHz, chloroform-d) δ 8.03 (d, J = 2.1 Hz, 1H), 7.47 - 7.40 (m, 2H), 7.39 - 7.33 (m, 3H), 7.33 - 7.28 (m, 1H), 7.03 (d, J = 2.1 Hz, 1H), 6.82 (d, J = 16.0 Hz, 1H), 6.38 (dt, J = 15.9, 5.6 Hz, 1H), 4.79 (dd, J = 5.6, 1.6 Hz, 2H).

[1331] 13 13C NMR (126 MHz, CDCl3) δ 154.83, 141.48, 136.08, 134.45, 132.21, 128.89, 128.87, 128.51, 126.89, 122.27, 118.94, 109.30, 70.41.

[1332] HRMS (APCI): Calcd for C 14 H 11 ClINO [M + H] + = 371.9647; Found [M + H] + = 371.9647.

[1333] Preparation Example 185: 3-Benzyl-6-chlorofuro[3,2-b]pyridine

[1334]

[1335] Pd(OAc)2 (5.4 mg, 0.024 mmol) was added to a degassed mixture of 5-chloro-3-(cinnamyloxy)-2-iodopyridine (Preparation Example 184; 150 mg, 0.404 mmol), K2CO3 (140 mg, 1.009 mmol), HCOONa (28 mg, 0.404 mmol), and tetrabutylammonium chloride (123 g, 0.444 mmol) in N,N-dimethylformamide (3 mL), and the reaction mixture was stirred at 80 °C for 3 h. The reaction mixture was diluted with EtOAc (30 mL) and extracted with brine (6 × 30 mL). The organic layer was dried over Na2SO4, filtered, and the solvent was evaporated in vacuo. Flash chromatography (cyclohexane) gave the white solid product (38 mg, 39% yield).

[1336] 11H NMR (500 MHz, chloroform-d) δ 8.14 (d, J = 2.0 Hz, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.35 (t, J = 3.2 Hz, 1H), 7.29 (dd, J = 9.9, 8.3 Hz, 3H), 7.16 (d, J = 2.0 Hz, 1H), 5.58 (d, J = 3.2 Hz, 2H).

[1337] 13 13C NMR (126 MHz, CDCl3) δ 156.96, 146.50, 141.73, 136.18, 132.55, 131.74, 129.11, 128.92, 128.89, 128.78, 128.01, 120.90, 117.21, 75.60.

[1338] HRMS (APCI): Calcd for C 14 H 10 ClNO [M+H] + = 244.0524; Found [M+H] + = 244.0525.

[1339] Preparation Example 186: 3-Benzyl-6-(4-(4-Methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridine

[1340]

[1341] Using 30 mg (0.123 mmol) of 3-benzyl-6-chlorofuro[3,2-b]pyridine (Preparation Example 185) and 45 mg (0.148 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by the general procedure B; the reaction time was 3 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 10:1) gave the compound as a pale yellow solid (16 mg, 34% yield).

[1342] 1 1H NMR (500 MHz, chloroform-d) δ 8.42 (d, J = 1.8 Hz, 1H), 7.55 - 7.49 (m, 2H), 7.43 (dd, J = 8.3, 7.1 Hz, 2H), 7.36 (t, J = 3.2 Hz, 1H), 7.34 - 7.28 (m, 4H), 7.05 - 6.97 (m, 2H), 5.58 (d, J = 3.2 Hz, 2H), 3.33 (t, J = 5.2 Hz, 4H), 2.64 (s, 4H), 2.40 (s, 3H).

[1343] 1313C NMR (126 MHz, CDCl3) δ 157.24, 151.23, 145.84, 141.62, 137.47, 136.69, 133.92, 129.04, 128.79, 128.05, 127.56, 119.44, 116.25, 114.31, 75.08, 55.05, 48.60, 46.14.

[1344] HRMS (APCI): Calcd for C 25 H 25 N3O [M + H] + = 384.2070; Found [M + H] + = 384.2067.

[1345] Preparation Example 187: 6-Chloro-7-methyl-3-phenylfuro[3,2-b]pyridine

[1346]

[1347] Under argon, n-BuLi (2.5 M hexane solution, 0.226 mL, 0.566 mmol) was added dropwise to a cold (-78 °C) solution of 6-chloro-3-phenylfuro[3,2-b]pyridine (Preparation Example 100; 100 mg, 0.435 mmol) in THF (6 mL), and the resulting mixture was stirred at -78 °C for 1 h. A solution of methyl iodide (0.054 mL, 0.871 mmol) in THF (2 mL) was added dropwise at -78 °C, the reaction mixture was heated to 25 °C, and stirred at 25 °C for 1 h. The mixture was quenched with brine (1 mL) and the solvent was evaporated. The residue was purified by flash chromatography (cyclohexane / toluene, gradient 1:0 to 10:1) to give a pale yellow solid product (24 mg, 23%).

[1348] 1 1H NMR (500 MHz, deuterochloroform) δ 8.58 (s, 1H), 8.09 (s, 1H), 8.07 - 7.98 (m, 2H), 7.51 - 7.45 (m, 2H), 7.40 - 7.32 (m, 1H), 2.60 (s, 3H).

[1349] 13 13C NMR (126 MHz, CDCl3) δ 148.58, 145.56, 145.01, 143.65, 130.30, 129.03, 128.96, 128.37, 128.04, 127.29, 127.26, 122.34, 77.16, 12.39.

[1350] HRMS (APCI): Calcd for C 14H 10 ClNO[M+H] + = 244.0524; Measured value [M+H] + = 244.0527.

[1351] Preparation Example 188: 7-Methyl-6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-phenylfuro[3,2-b] pyridine

[1352]

[1353] Using 24 mg (0.098 mmol) of 6-chloro-7-methyl-3-phenylfuro[3,2-b]pyridine (Preparation Example 187) and 36 mg (0.118 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 3 hours; flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1) gave the compound as a white solid (34 mg, 90% yield).

[1354] 1 H NMR (500 MHz, chloroform-d) δ 8.54 (s, 1H), 8.11 (s, 1H), 8.11 - 8.05 (m, 3H), 7.52 - 7.45 (m, 3H), 7.39 - 7.32 (m, 1H), 7.34 - 7.27 (m, 2H), 7.05 - 7.01 (m, 3H), 3.37 - 3.29 (m, 5H), 2.65 (dd, J = 6.2, 3.9 Hz, 6H), 2.52 (s, 3H), 2.40 (s, 3H).

[1355] 13 C NMR (126 MHz, CDCl3) δ 150.58, 149.12, 147.38, 144.39, 143.72, 133.90, 130.96, 130.79, 129.01, 129.99, 128.55, 128.30, 127.90, 127.73, 127.29, 122.24, 116.41, 115.77, 55.21, 48.79, 46.20, 12.68.

[1356] HRMS (APCI): Calculated for C 25 H 25 N3O[M+H] + = 384.2070; Measured value [M+H] + = 384.2068.

[1357] Preparation Example 189: 6-Chloro-3-(phenylethynyl)furo[3,2-b]pyridine

[1358]

[1359] 0.092 mL (0.839 mmol) of phenylacetylene, 13.6 mg (0.0194 mmol) of PdCl2(PPh3)2, and 12 mg (0.0645 mmol) of CuI were placed into a degassed solution of 3-bromo-6-chlorofuro[3,2-b]pyridine (150 mg, 0.645 mmol; Preparation Example 5) in 5 mL of anhydrous 1,4-dioxane and 0.99 mL (7.10 mmol) of anhydrous triethylamine. The reaction mixture was stirred at 95 °C for 30 h, and the reaction progress was monitored by TLC. The reaction mixture was hot-filtered through a 535 / SiO2 = 3 / 1 (8 g) pad. The filter pad was washed with 3 x 10 mL of EtOAc, and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 96:4) gave the white solid compound (143 mg, 87% yield).

[1360] 1 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J = 2.1 Hz, 1H), 8.02 (s, 1H), 7.76 (d, J = 2.0 Hz, 1H), 7.54 (dd, J = 7.1, 3.4 Hz, 2H), 7.31 - 7.27 (m, 3H).

[1361] 13 13C NMR (126 MHz, CDCl3) δ 151.66, 147.31, 144.83, 131.89, 128.76, 128.34, 128.32, 122.62, 119.08, 106.58, 95.60, 76.23.

[1362] HRMS (APCI): calculated for C 15 H8ClNO [M+H] + = 254.0367; found [M+H] + = 254.0366.

[1363] Preparation Example 190: tert-Butyl 4-(4-(3-(phenylethynyl)furo[3,2-b]pyridin-6-yl)phenyl) piperazine-1-carboxylate

[1364]

[1365] Using 50 mg (0.197 mmol) of 6-chloro-3-(phenylethynyl)furo[3,2-b]pyridine (Preparation Example 189) and 100 mg (0.256 mmol) of tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate, the compound was prepared by General Procedure B. The reaction time was 3 hours. Instead of extracting the reaction mixture, it was hot filtered through a 535 / SiO2 = 3 / 1 (4 g) pad and concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 10:1 to 2:1) gave the compound as an off-white solid (65 mg, 69% yield).

[1366] 1 1H NMR (500 MHz, CDCl3) δ 8.90 (d, J = 1.8 Hz, 1H), 8.12 (s, 1H), 7.94 (d, J = 1.8 Hz, 1H), 7.68 - 7.62 (m, 2H), 7.58 (d, J = 8.9 Hz, 2H), 7.38 (dd, J = 4.6, 2.3 Hz, 3H), 7.06 (d, J = 8.9 Hz, 2H), 3.65 - 3.62 (m, 4H), 3.27 - 3.23 (m, 4H), 1.52 (s, 9H).

[1367] 13 13C NMR (126 MHz, CDCl3) δ 154.72, 151.10, 151.05, 148.24, 145.75, 144.74, 133.78, 131.88, 129.03, 128.55, 128.28, 122.93, 116.69, 116.26, 106.32, 95.15, 80.01, 48.90, 43.39, 28.45.

[1368] HRMS (APCI): Calcd for C 30 H 29 N3O3 [M + H] + = 480.2282; Found [M + H] + = 480.2285.

[1369] Preparation Example 191: 1-{4-[3-(2-Phenylethynyl)furo[3,2-b]pyridin-6-yl]phenyl}piperazine

[1370]

[1371] At 0 °C, 1.83 mL (7.3 mmol) of 4 M HCl in 1,4-dioxane was added to a 7.0 mL MeOH solution of 50 mg (0.104 mmol) of tert-butyl 4-(4-(3-(phenylethynyl)furo[3,2-b]pyridin-6-yl)phenyl)piperazine-1-carboxylate (Preparation Example 190). The mixture was stirred at 0 °C for 70 minutes. The ice bath was removed and the mixture was stirred for an additional 2 hours. The reaction mixture was concentrated in vacuo. To the residue was added 0.20 g of solid sodium bicarbonate (2.288 mmol), and the mixture was mixed with a 12.0 mL mixture of DCM / MeOH = 5:1 and stirred for 2.5 hours. The mixture was filtered hot through a 535 / SiO2 = 1 / 1 (8 g) pad and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 20:1 to 2:1) gave the title compound as an off-white solid (18 mg, 45% yield).

[1372] 1 1H NMR (500 MHz, MeOD) δ 8.82 (d, J = 1.8 Hz, 1H), 8.41 (s, 1H), 8.22 (d, J = 1.8 Hz, 1H), 7.71 - 7.63 (m, 4H), 7.43 (dd, J = 4.8, 2.1 Hz, 3H), 7.17 (d, J = 8.9 Hz, 2H), 3.45 - 3.41 (m, 4H), 3.28 - 3.25 (m, 4H).

[1373] 13 13C NMR (126 MHz, MeOD) δ 152.17, 150.84, 148.67, 144.47, 144.03, 134.23, 131.30, 128.87, 128.50, 128.17, 127.92, 122.78, 116.78, 116.63, 105.41, 94.69, 76.22, 44.02.

[1374] HRMS (APCI): Calcd for C 25 H 21 N3O [M + H] + = 380.1757; Found [M + H] + = 380.1756.

[1375] Preparation Example 192: 5-Chloro-2-iodopyridin-3-yl acetate

[1376]

[1377] 5-Chloro-2-iodopyridin-3-ol (Preparation Example 1; 1.79 g, 7.008 mmol) was mixed with acetic anhydride (5.0 mL, 53.0 mmol), and the mixture was stirred at 125 °C for 30 minutes. Saturated aqueous NaHCO3 solution (80 mL) was added, and the mixture was extracted with ethyl acetate (100 mL). The organic phase was washed with saturated aqueous NaHCO3 solution (50 mL, until the release of CO2 ceased), and the organic portion was concentrated, and all volatiles were evaporated in vacuo. A pale yellow solid product (1.554 g, 75% yield) was obtained.

[1378] 1 1H NMR (500 MHz, chloroform-d) δ 8.27 (d, J = 2.3 Hz, 1H), 7.41 (d, J = 2.3 Hz, 1H), 2.40 (s, 3H).

[1379] 13 13C NMR (126 MHz, CDCl3) δ 167.81, 148.88, 146.84, 132.05, 130.31, 112.26, 21.32.

[1380] HRMS (APCI): Calcd for C7H5ClINO2 [M+H] + = 297.9126; Found [M+H] + = 297.9127.

[1381] Preparation Example 193: 5-Chloro-2-(3-(trimethylsilyl)prop-1-yn-1-yl)pyridin-3-yl acetate

[1382]

[1383] To a degassed solution of 5-chloro-2-iodopyridin-3-yl acetate (Preparation Example 192; 500 mg, 1.681 mmol) in a mixture of 1,4-dioxane (3 mL) and TEA (2 mL) was added 3-(trimethylsilyl)prop-1-yne (245 mg, 2.185 mmol), PdCl2(PPh3)2 (35 mg, 0.050 mmol), and CuI (19 mg, 0.101 mmol), and the resulting mixture was stirred at 45 °C for 2 hours. The solvent was evaporated in vacuo, and the residue was purified by flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 6:1). A colorless oil product (366 mg, 77% yield) was obtained.

[1384] 1 1H NMR (500 MHz, chloroform-d) δ 8.37 (d, J = 2.2 Hz, 1H), 7.46 (d, J = 2.2 Hz, 1H), 2.34 (s, 3H), 1.79 (s, 2H), 0.17 (s, 9H).

[1385] 13 13C NMR (126 MHz, CDCl3) δ 168.17, 148.00, 146.11, 136.76, 130.06, 129.80, 96.76, 74.66, 20.99, 8.72, -1.79.

[1386] HRMS (APCI): Calcd for C 13 H 16 ClNO2Si [M + H] + = 282.0712; Found [M + H] + = 282.0714.

[1387] Preparation Example 194: 6-Chloro-3-iodo-2-methylfuro[3,2-b]pyridine

[1388]

[1389] To a solution of 5-chloro-2-(3-(trimethylsilyl)prop-1-yn-1-yl)pyridin-3-yl acetate (Preparation Example 193; 366 mg, 1.299 mmol) in MeOH (10 mL) was added a solution of iodine (989 mg, 3.896 mmol) in MeOH (10 mL) and CsHCO3 (756 mg, 3.896 mmol). The resulting mixture was stirred at 40 °C for 2 h in a flask wrapped with aluminum foil. A solution of Na2S2O3 (1.289 g, 5.195 mmol) in H2O (3 mL) was added, and the mixture was concentrated to dryness in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 97:3) to give the product as a colorless oil (200 mg, 53% yield).

[1390] 1 1H NMR (500 MHz, chloroform-d) δ 8.49 (d, J = 2.0 Hz, 1H), 7.64 (d, J = 2.0 Hz, 1H), 2.58 (s, 3H).

[1391] 13 13C NMR (126 MHz, CDCl3) δ 161.04, 147.47, 146.94, 145.35, 127.73, 118.06, 65.46, 14.76.

[1392] HRMS (APCI): Calcd for C8H5ClINO [M + H] + = 293.9177; Found [M + H] + = 293.9180.

[1393] Preparation Example 195: 6-Chloro-2-methyl-3-phenylfuro[3,2-b]pyridine

[1394]

[1395] Using 185 mg (0.630 mmol) of 6-chloro-3-iodo-2-methylfuro[3,2-b]pyridine (Preparation Example 194) and 100 mg (0.819 mmol) of phenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1) gave the compound as a pale yellow solid (98 mg, 64% yield).

[1396] 1 1H NMR (500 MHz, chloroform-d) δ 8.51 (d, J = 2.0 Hz, 1H), 7.72 (d, J = 2.1 Hz, 1H), 7.72 - 7.66 (m, 2H), 7.50 (t, J = 7.7 Hz, 2H), 7.38 (t, J = 7.5 Hz, 1H), 2.64 (s, 3H).

[1397] 13 13C NMR (126 MHz, CDCl3) δ 156.86, 146.89, 146.48, 144.72, 130.65, 129.16, 128.94, 127.67, 126.70, 117.72, 117.50, 13.95.

[1398] HRMS (APCI): Calcd for C 14 H 10 ClNO [M + H] + = 244.0524; Found [M + H] + = 244.0522.

[1399] Preparation Example 196: 1-Methyl-4-(4-{2-Methyl-3-phenylfuro[3,2-b]pyridin-6-yl}phenyl) piperazine

[1400]

[1401] Using 93 mg (0.382 mmol) of 6-chloro-2-methyl-3-phenylfuro[3,2-b]pyridine (Preparation Example 195) and 150 mg (0.496 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 3 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a pale yellow solid (62 mg, 42% yield).

[1402] 1 1H NMR (500 MHz, chloroform-d) δ 8.77 (d, J = 1.9 Hz, 1H), 7.82 (d, J = 1.9 Hz, 1H), 7.75 (dd, J = 8.2, 1.3 Hz, 2H), 7.55 (d, J = 8.7 Hz, 2H), 7.51 (t, J = 7.8 Hz, 2H), 7.41 - 7.32 (m, 1H), 7.04 (d, J = 8.8 Hz, 2H), 3.34 - 3.20 (m, 4H), 2.66 (s, 3H), 2.64 - 2.59 (m, 4H), 2.38 (s, 3H).

[1403] 13 13C NMR (126 MHz, CDCl3) δ 155.84, 151.02, 147.72, 146.39, 144.55, 132.31, 131.35, 129.41, 129.19, 128.88, 128.19, 127.36, 117.41, 116.40, 115.01, 55.19, 48.89, 46.29, 13.97.

[1404] HRMS (APCI): Calcd for C 25 H 25 N3O [M + H] + = 384.2070; Found [M + H] + = 384.2070.

[1405] Preparation Example 197: 5-Chloro-2-(pent-1-yn-1-yl)pyridin-3-yl acetate

[1406]

[1407] To a degassed solution of 5-chloro-2-iodopyridin-3-yl acetate (Preparation Example 192; 756 mg, 2.541 mmol) in 1,4-dioxane (10 mL) and TEA (10 mL) was added pent-1-yne (0.326 mL, 3.304 mmol), PdCl2(PPh3)2 (54 mg, 0.076 mmol), and CuI (29 mg, 0.152 mmol). The resulting mixture was stirred at 45 °C for 2 h. The solvent was evaporated in vacuo and the residue was purified by flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 10:1). A brown oil product was obtained (604 mg, 100% yield).

[1408] 11H NMR (500 MHz, chloroform-d) δ 8.39 (d, J = 2.1 Hz, 1H), 7.48 (d, J = 2.2 Hz, 1H), 2.45 (t, J = 7.0 Hz, 2H), 2.35 (s, 3H), 1.65 (q, J = 7.2 Hz, 2H), 1.06 (t, J = 7.4 Hz, 3H).

[1409] 13 13C NMR (126 MHz, CDCl3) δ 168.11, 148.36, 146.20, 136.24, 130.47, 130.16, 97.68, 75.64, 21.92, 21.66, 20.91, 13.65.

[1410] HRMS (APCI): Calcd for C 12 H 12 ClNO2 [M+H] + = 238.0629; Found [M+H] + = 238.0627.

[1411] Preparation Example 198: 6-Chloro-3-iodo-2-propylfuro[3,2-b]pyridine

[1412]

[1413] To a solution of 5-chloro-2-(pent-1-yn-1-yl)pyridin-3-yl acetate (Preparation Example 197; 584 mg, 2.457 mmol) in MeOH (10 mL) was added a solution of iodine (1.871 g, 7.371 mmol) in MeOH (10 mL) and CsHCO3 (1.429 g, 7.371 mmol). The resulting mixture was stirred at 40 °C for 2 h in a flask wrapped with aluminum foil. A solution of Na2S2O3 (2.439 g, 9.828 mmol) in H2O (5 mL) was added, and the mixture was concentrated to dryness in vacuo. The residue was purified by flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 9:1) to give the product as a white solid (556 mg, 70% yield).

[1414] 1 1H NMR (500 MHz, chloroform-d) δ 8.52 (d, J = 2.0 Hz, 1H), 7.68 (d, J = 2.0 Hz, 1H), 2.90 (t, J = 7.4 Hz, 2H), 1.81 (q, J = 7.4 Hz, 2H), 1.01 (t, J = 7.4 Hz, 3H).

[1415] 1313C NMR (126 MHz, CDCl3) δ 164.43, 147.44, 147.04, 145.34, 127.77, 118.23, 65.31, 30.65, 21.16, 13.77.

[1416] HRMS (APCI): Calcd for C 10 H9ClINO [M+H] + = 321.9490; Found [M+H] + = 321.9491.

[1417] Preparation Example 199: 6-Chloro-3-phenyl-2-propylfuro[3,2-b]pyridine

[1418]

[1419] Using 100 mg (0.311 mmol) of 6-chloro-3-iodo-2-propylfuro[3,2-b]pyridine (Preparation Example 198) and 49 mg (0.404 mmol) of phenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane) gave a pale yellow solid compound (77 mg, 91% yield).

[1420] 1 1H NMR (300 MHz, chloroform-d) δ 8.50 (d, J = 2.0 Hz, 1H), 7.73 (d, J = 2.1 Hz, 1H), 7.68 - 7.61 (m, 2H), 7.55 - 7.46 (m, 2H), 7.43 - 7.34 (m, 1H), 2.98 - 2.86 (m, 2H), 1.92 - 1.76 (m, 2H), 1.01 (t, J = 7.4 Hz, 3H).

[1421] 13 13C NMR (126 MHz, CDCl3) δ 160.68, 146.92, 146.52, 144.67, 130.63, 129.35, 128.92, 128.87, 127.72, 126.88, 126.71, 117.83, 117.57, 29.55, 21.52, 14.01.

[1422] HRMS (APCI): Calcd for C 16 H 14 ClNO [M+H] + = 272.0837; Found [M+H] + = 272.0840.

[1423] Preparation Example 200: 1-Methyl-4-(4-{3-phenyl-2-propylfuro[3,2-b]pyridin-6-yl}phenyl) piperazine

[1424]

[1425] Using 69 mg (0.254 mmol) of 6-chloro-3-phenyl-2-propylfuro[3,2-b]pyridine (Preparation Example 199) and 100 mg (0.330 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 3 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a pale yellow solid (37 mg, 35% yield).

[1426] 1 H NMR (500 MHz, DMSO-d6) δ 8.78 (d, J = 2.0 Hz, 1H), 8.19 (d, J = 1.9 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.65 (d, J = 8.9 Hz, 2H), 7.53 (t, J = 7.7 Hz, 2H), 7.45 - 7.36 (m, 1H), 7.06 (d, J = 8.9 Hz, 2H), 3.29 (s, 1H), 3.25 - 3.18 (m, 4H), 2.98 (t, J = 7.5 Hz, 2H), 2.47 (t, J = 5.1 Hz, 4H), 2.24 (s, 3H), 1.81 (h, J = 7.4 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H).

[1427] 13 C NMR (126 MHz, DMSO) δ 159.03, 150.60, 147.01, 145.12, 143.62, 131.67, 130.66, 128.91, 128.48, 127.58, 127.25, 127.21, 116.34, 115.54, 114.58, 54.45, 47.69, 45.72, 28.87, 20.80, 13.61.

[1428] HRMS (APCI): Calcd for C 27 H 29 N3O [M + H] + = 412.2383; Found [M + H] + = 412.2383.

[1429] Preparation Example 201: 6-Chloro-3-(1-phenylethenyl)furo[3,2-b]pyridine

[1430]

[1431] Using 150 mg (0.645 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 124 mg (0.839 mmol) of 1-(vinylphenyl)boronic acid, the compound was prepared by General Procedure A; the reaction time was 3 hours. The reaction mixture was hot-filtered through a 535 / SiO2 = 3 / 1 (4 g) pad, washed with 3 x 10 mL of EtOAc, and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 99:1) gave the compound as a white solid (145 mg, 88% yield).

[1432] 1 1H NMR (500 MHz, CDCl3) δ 8.63 (d, J = 2.0 Hz, 1H), 7.82 (d, J = 2.1 Hz, 1H), 7.66 (s, 1H), 7.51 - 7.46 (m, 2H), 7.44 - 7.36 (m, 3H), 6.62 (d, J = 1.5 Hz, 1H), 5.64 (d, J = 1.5 Hz, 1H).

[1433] 13 13C NMR (126 MHz, CDCl3) δ 148.35, 148.22, 145.12, 144.70, 140.91, 138.32, 128.46, 128.00, 127.91, 127.59, 121.90, 118.64, 117.82.

[1434] HRMS (APCI): Calcd for C 15 H 10 ClNO [M+H] + = 256.0524; Found [M+H] + = 256.0523.

[1435] Preparation Example 202: 6-(4-(4-Methylpiperazin-1-yl)phenyl)-3-(1-phenylethenyl)furo[3,2- b]pyridine

[1436]

[1437] Using 82 mg (0.321 mmol) of 6-chloro-3-(1-phenylethenyl)furo[3,2-b]pyridine (Preparation Example 201) and 107 mg (0.353 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B. The reaction time was 1 hour. The reaction mixture was passed through a 535 / SiO2 = 3 / 1 (4 g) pad hot filtration. Wash the pad with 3 x 10 mL EtOAc and 10 mL MeOH. Concentrate the filtrate in vacuo. Flash chromatography (DCM / MeOH, gradient 1:0 to 96:4) gave an off-white solid compound (43 mg, 34% yield).

[1438] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 2.0 Hz, 1H), 7.92 (d, J = 1.8 Hz, 1H), 7.65 (s, 1H), 7.59 (d, J = 8.9 Hz, 2H), 7.52 (dd, J = 8.1, 1.5 Hz, 2H), 7.45 - 7.36 (m, 3H), 7.07 (d, J = 8.9 Hz, 2H), 6.69 (d, J = 1.8 Hz, 1H), 5.65 (d, J = 1.7 Hz, 1H), 3.36 - 3.30 (m, 4H), 2.67 - 2.61 (m, 4H), 2.40 (s, 3H).

[1439] 13 13C NMR (126 MHz, CDCl3) δ 151.02, 149.25, 147.52, 144.90, 144.58, 141.28, 138.84, 133.04, 128.79, 128.39, 128.13, 128.00, 127.87, 121.84, 117.33, 116.19, 115.81, 55.03, 48.66, 46.14.

[1440] HRMS (APCI): Calcd for C 26 H 25 N3O [M + H] + = 396.2070; Found [M + H] + = 396.2067.

[1441] Preparation Example 203: 1-Methyl-4-{4-[3-(1-phenylethyl)furo[3,2-b]pyridin-6-yl]phenyl} piperazine

[1442]

[1443] A mixture of 100 mg (0.253 mmol) of 6-(4-(4-methylpiperazin-1-yl)phenyl)-3-(1-phenylethenyl)furo[3,2-b]pyridine (Preparation Example 202) and 300 mg (0.282 mmol) of 10% Pd / C in 20 mL of MeOH was hydrogenated at 10 bar and 23 °C for 2 h. Through a syringe filter ( Filter the reaction mixture through Xtra PTFE-20 / 25 (0.25 μm) and concentrate the filtrate in vacuo. Flash chromatography (DCM / MeOH, gradient from 1:0 to 96:4) afforded the compound as an off-white solid (13 mg, 13% yield).

[1444] 1 1H NMR (500 MHz, CDCl3) δ 8.78 (d, J = 2.0 Hz, 1H), 7.84 (d, J = 2.0 Hz, 1H), 7.54 (d, J = 8.9 Hz, 2H), 7.50 (s, 1H), 7.44 (d, J = 7.8 Hz, 2H), 7.35 (t, J = 7.7 Hz, 2H), 7.27 - 7.22 (m, 1H), 7.04 (d, J = 8.9 Hz, 2H), 4.52 (q, J = 6.9 Hz, 1H), 3.39 - 3.30 (m, 4H), 2.72 - 2.61 (m, 4H), 2.42 (s, 3H), 1.82 (d, J = 7.2 Hz, 3H).

[1445] 13 13C NMR (126 MHz, CDCl3) δ 150.77, 148.97, 145.32, 145.30, 144.64, 144.49, 132.75, 129.23, 128.50, 128.11, 127.43, 126.70, 126.46, 116.27, 115.67, 54.93, 48.56, 45.99, 34.93, 21.26.

[1446] HRMS (APCI): Calcd for C 26 H 27 N3O [M + H] + = 398.2227; Found [M + H] + = 398.2225.

[1447] Preparation Example 204: 6-Chloro-3-(pyrimidin-5-yl)furo[3,2-b]pyridine

[1448]

[1449] The compound was prepared by General Procedure A using 150 mg (0.645 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 104 mg (0.839 mmol) of pyrimidin-5-ylboronic acid. The reaction time was 2 h. The reaction mixture was passed through a mixture 535 / SiO2 = 3 / 1 (4 g) pad hot filtration, and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient 1:0 to 94:6) gave the white solid compound (64 mg, 43% yield).

[1450] 1 1H NMR (500 MHz, CDCl3) δ 9.44 (s, 2H), 9.25 (s, 1H), 8.68 (d, J = 2.1 Hz, 1H), 8.27 (s, 1H), 7.92 (d, J = 2.1 Hz, 1H).

[1451] 13 13C NMR (126 MHz, CDCl3) δ 157.93, 154.69, 148.34, 145.96, 145.80, 143.38, 128.52, 124.73, 119.13, 116.15.

[1452] HRMS (APCI): Calcd for C 11 H6ClN3O [M+H] + = 232.0272; Found [M+H] + = 232.0275.

[1453] Preparation Example 205: tert-Butyl 4-(4-(3-(pyrimidin-5-yl)furo[3,2-b]pyridin-6-yl)phenyl)pi perazine-1-carboxylate

[1454]

[1455] Using 50 mg (0.216 mmol) of 6-chloro-3-(pyrimidin-5-yl)furo[3,2-b]pyridine (Preparation Example 204) and 109 mg (0.281 mmol) of tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine-1-carboxylate, the compound was prepared by General Procedure B. The reaction time was 2 h. The reaction mixture was filtered through 535 / SiO2 = 3 / 1 (4 g) pad hot filtration, and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient 1:0 to 97:3) afforded the white solid compound (99 mg, 100% yield).

[1456] 11H NMR (500 MHz, CDCl3) δ 9.40 (s, 2H), 9.15 (s, 1H), 8.82 (d, J = 1.8 Hz, 1H), 8.16 (s, 1H), 7.89 (d, J = 1.8 Hz, 1H), 7.51 (d, J = 8.9 Hz, 2H), 6.98 (d, J = 9.0 Hz, 2H), 3.57 - 3.52 (m, 4H), 3.19 - 3.14 (m, 4H), 1.43 (s, 9H).

[1457] 13 13C NMR (126 MHz, CDCl3) δ 157.68, 154.70, 151.15, 149.29, 145.60, 145.10, 143.29, 133.82, 128.84, 128.25, 125.35, 116.68, 116.19, 115.96, 80.03, 48.84, 43.49, 28.45, 24.87.

[1458] HRMS (APCI): Calcd for C 26 H 27 N5O3 [M + H] + = 458.2187; Found [M + H] + = 458.2191.

[1459] Preparation Example 206: 5-{6-[4-(Piperazin-1-yl)phenyl]furo[3,2-b]pyridin-3-yl}pyrimidine

[1460]

[1461] A solution of 3.5 mL of 4 M HCl (14.075 mmol) in 1,4 - dioxane was added dropwise to a mixture of 92 mg (0.201 mmol) of tert - butyl 4-(4-(3-(pyrimidin - 5 - yl)furo[3,2 - b]pyridin - 6 - yl)phenyl)piperazine - 1 - carboxylate (Preparation Example 205) in 10 mL of MeOH at 0 °C and the mixture was stirred for 30 minutes. The ice bath was removed and the mixture was stirred for an additional 60 minutes. The reaction mixture was concentrated in vacuo, 0.50 g of solid sodium bicarbonate (5.952 mmol) was added to the residue, and the mixture was mixed with 12 mL of a 5 / 1 mixture of DCM / MeOH and stirred for 3 hours. The mixture was filtered through a 535 / SiO2 = 1 / 1 (6 g) pad and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient 20:1 to 2:1) gave the compound as an off - white solid (47 mg, 66% yield).

[1462] 11H NMR (500 MHz, DMSO) δ 9.62 (s, 2H), 9.20 (s, 1H), 9.05 (s, 1H), 8.99 (d, J = 1.8 Hz, 1H), 8.39 (d, J = 2.0 Hz, 1H), 7.73 (d, J = 8.9 Hz, 2H), 7.09 (d, J = 8.9 Hz, 2H), 3.27 - 3.22 (m, 4H), 3.01 - 2.96 (m, 4H).

[1463] 13 13C NMR (126 MHz, DMSO) δ 157.69, 154.67, 151.49, 149.30, 148.32, 145.31, 143.16, 133.35, 128.35, 127.38, 125.69, 116.46, 116.15, 115.05, 48.25, 45.11.

[1464] HRMS (APCI): Calcd for C 21 H 19 N5O [M + H] + = 358.1662; Found [M + H] + = 358.1662.

[1465] Preparation Example 207: 6-Chloro-3-(1,5-dimethyl-1H-pyrazol-4-yl)furo[3,2-b]pyridine

[1466]

[1467] Using 150 mg (0.645 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 186 mg (0.839 mmol) of 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the compound was prepared by General Procedure A. The reaction time was 3 hours. The reaction mixture was filtered hot through a 535 / SiO2 = 3 / 1 (4 g) pad and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 1:0 to 94:6) gave the compound as a pale beige solid (145 mg, 91% yield).

[1468] 1 1H NMR (500 MHz, CDCl3) δ 8.59 (d, J = 2.1 Hz, 1H), 7.94 (s, 1H), 7.87 (s, 1H), 7.83 (d, J = 2.0 Hz, 1H), 3.90 (s, 3H), 2.45 (s, 3H).

[1469] 1313C NMR (126 MHz, CDCl3) δ 147.77, 145.06, 144.92, 144.54, 138.06, 136.43, 127.54, 118.56, 115.47, 107.93, 36.55, 10.88.

[1470] HRMS (APCI): Calcd for C 12 H 10 ClN3O [M+H] + = 248.0585; Found [M+H] + = 248.0586.

[1471] Preparation Example 208: 3-(1,5-Dimethyl-1H-pyrazol-4-yl)-6-(4-(4-methylpiperazin-1-yl)phenyl) furo[3,2-b]pyridine

[1472]

[1473] Using 124 mg (0.500 mmol) of 6-chloro-3-(1,5-dimethyl-1H-pyrazol-4-yl)furo[3,2-b]pyridine (Preparation Example 207) and 197 mg (0.650 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B. The reaction time was 3.5 h. The reaction mixture was filtered through a 535 / SiO2 = 3 / 1 (4 g) pad by hot filtration, and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 1:0 to 20:1) gave the compound as an off-white solid (50 mg, 26% yield).

[1474] 1 1H NMR (500 MHz, CDCl3) δ 8.85 (d, J = 1.8 Hz, 1H), 7.96 (s, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.86 (s, 1H), 7.58 (d, J = 8.9 Hz, 2H), 7.06 (d, J = 8.9 Hz, 2H), 3.91 (s, 3H), 3.36 - 3.28 (m, 4H), 2.67 - 2.59 (m, 4H), 2.48 (s, 3H), 2.40 (s, 3H).

[1475] 1313C NMR (126 MHz, CDCl3) δ 150.99, 148.66, 144.88, 144.81, 143.90, 138.10, 136.40, 133.03, 128.90, 128.13, 116.19, 115.76, 115.30, 108.55, 55.03, 48.69, 46.15, 36.53, 10.89。

[1476] Preparation Example 209: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-4-fluorobenzonitrile

[1477]

[1478] Using 312 mg (1.342 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 266 mg (1.611 mmol) of (5-cyano-2-fluorophenyl)boronic acid, the compound was prepared by General Procedure A. The reaction time was 6 hours. The reaction mixture was filtered through a 535 / SiO2 = 3 / 1 (4 g) pad while hot, and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 94:6) gave the white solid compound (109 mg, 30% yield).

[1479] 1 1H NMR (500 MHz, CDCl3) δ 9.31 (dd, J = 6.9, 2.2 Hz, 1H), 8.59 (d, J = 2.1 Hz, 1H), 8.36 (d, J = 3.2 Hz, 1H), 7.82 (d, J = 2.0 Hz, 1H), 7.57 (ddd, J = 8.5, 4.7, 2.2 Hz, 1H), 7.23 (dd, J = 10.7, 8.5 Hz, 1H).

[1480] 13 13C NMR (126 MHz, CDCl3) δ 163.07, 161.01, 149.40, 149.26, 147.64, 145.49, 143.57, 134.22, 134.18, 132.83, 132.75, 128.30, 120.37, 120.25, 118.99, 118.15, 117.02, 116.82, 113.13, 113.11, 109.29, 109.26.

[1481] 19 19F NMR (471 MHz, CDCl3) δ -101.77.

[1482] HRMS (APCI): Calculated for C 14H6ClFN2O[M+H] + = 273.0225; Measured value [M+H] + = 273.0227.

[1483] Preparation Example 210: 4-Fluoro-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzonitrile

[1484]

[1485] Using 109 mg (0.398 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-4-fluorobenzonitrile (Preparation Example 209) and 144 mg (0.478 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B. The reaction time was 2.5 hours. The reaction mixture was filtered through a 535 / SiO2 = 3 / 1 (4 g) pad while hot, and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 1:0 to 97:3) gave the compound as an off-white solid (139 mg, 85% yield).

[1486] 1 H NMR (500 MHz, DMSO-d6) δ 9.33 (dd, J = 6.9, 2.1 Hz, 1H), 9.03 (d, J = 2.0 Hz, 1H), 8.83 (d, J = 3.1 Hz, 1H), 8.41 (d, J = 2.0 Hz, 1H), 7.98 (ddd, J = 8.5, 4.7, 2.1 Hz, 1H), 7.72 (d, J = 8.9 Hz, 2H), 7.67 (dd, J = 10.8, 8.5 Hz, 1H), 7.08 (d, J = 9.0 Hz, 2H), 3.26 - 3.21 (m, 4H), 2.49 - 2.46 (m, 4H), 2.24 (s, 3H).

[1487] 13 C NMR (126 MHz, DMSO-d6) δ 163.06, 161.01, 151.38, 150.11, 149.99, 148.68, 145.19, 143.10, 134.00, 133.92, 133.85, 133.81, 133.44, 128.30, 127.03, 120.73, 120.61, 118.64, 118.29, 118.10, 116.38, 116.00, 112.55, 108.64, 108.61, 54.97, 48.11, 46.26.

[1488] HRMS(APCI): Calculated value C 25 H 21 FN4O[M+H] + = 413.1772; Measured value [M+H] + = 413.1774.

[1489] Preparation Example 211: 4-Fluoro-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzamide

[1490]

[1491] Ghaffar-Parkins catalyst (3.9 mg, 0.009 mmol) was added to a solution of 37 mg (0.091 mmol) of 4-fluoro-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzonitrile (Preparation Example 210) in a mixture of EtOH (2 mL) and H2O (1 mL). The reaction mixture was stirred at 80 °C for 16 h, and the reaction mixture was filtered hot through a 535 / SiO2 = 3 / 1 (4 g) pad. The filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 1:0 to 94:6) gave the title compound as an off-white solid (28 mg, 72% yield).

[1492] 1 H NMR (500 MHz, DMSO-d6) δ 9.22 (dd, J = 7.4, 2.4 Hz, 1H), 9.00 (d, J = 1.8 Hz, 1H), 8.72 (d, J = 2.9 Hz, 1H), 8.37 (d, J = 2.0 Hz, 1H), 8.02 (s, 1H), 7.93 (ddd, J = 8.7, 4.9, 2.4 Hz, 1H), 7.73 (d, J = 8.9 Hz, 2H), 7.47 (dd, J = 10.8, 8.5 Hz, 1H), 7.44 (s, 1H), 7.08 (d, J = 9.0 Hz, 2H), 3.26 - 3.22 (m, 4H), 2.50 - 2.46 (m, 4H), 2.25 (s, 3H).

[1493] 1313C NMR (126 MHz, DMSO-d6) δ 167.59, 162.38, 160.37, 151.31, 149.30, 149.19, 148.63, 144.98, 143.59, 133.14, 131.74, 130.57, 130.53, 128.83, 128.76, 128.28, 127.24, 118.66, 118.54, 116.14, 116.09, 116.03, 115.90, 114.24, 54.97, 48.13, 46.23。

[1494] HRMS (APCI): Calcd for C 25 H 23 FN4O2 [M + H] + = 431.1878; Found [M + H] + = 431.1881。

[1495] Preparation Example 212: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-2-fluorobenzonitrile

[1496]

[1497] Using 300 mg (1.291 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 255 mg (1.549 mmol) of (3-cyano-2-fluorophenyl)boronic acid, the compound was prepared by General Procedure A. The reaction time was 3 h. The reaction mixture was filtered hot through a 535 / SiO2 = 3 / 1 (4 g) pad, and the filtrate was concentrated in vacuo. Flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 94:6) gave the compound as a white solid (164 mg, 47% yield).

[1498] 1 1H NMR (500 MHz, CDCl3) δ 9.21 (td, J = 7.6, 1.8 Hz, 1H), 8.66 (d, J = 2.0 Hz, 1H), 8.45 (d, J = 3.2 Hz, 1H), 7.92 (d, J = 2.1 Hz, 1H), 7.63 (ddd, J = 7.8, 6.0, 1.8 Hz, 1H), 7.46 (dd, J = 7.8, 7.8 Hz, 1H).

[1499] 1313C NMR (126 MHz, CDCl3) δ 160.24 (d, J = 262.0 Hz), 149.27 (d, J = 16.5 Hz), 147.74, 145.43, 143.69, 134.64, 134.61, 131.89, 128.25, 125.26, 125.24, 119.92 (d, J = 11.9 Hz), 119.07, 113.84, 113.33, 113.31, 102.01 (d, J = 15.6 Hz).

[1500] HRMS (APCI): Calcd for C 14 H6ClFN2O [M+H] + = 273.0225; Found [M+H] + = 273.0228.

[1501] Preparation Example 213: 2-Fluoro-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzonitrile

[1502]

[1503] Using 147 mg (0.540 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-2-fluorobenzonitrile (Preparation Example 212) and 196 mg (0.648 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B. The reaction time was 2.5 h. The reaction mixture was filtered hot through a 535 / SiO2 = 3 / 1 (4 g) pad, and the filtrate was concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient from 1:0 to 97:3) gave the compound as an off-white solid (133 mg, 60% yield).

[1504] 1 1H NMR (500 MHz, DMSO-d6) δ 9.15 (td, J = 7.8, 1.8 Hz, 1H), 8.97 (d, J = 1.8 Hz, 1H), 8.84 (d, J = 3.2 Hz, 1H), 8.41 (d, J = 1.8 Hz, 1H), 7.96 (ddd, J = 7.9, 6.2, 1.8 Hz, 1H), 7.72 (d, J = 9.0 Hz, 2H), 7.63 (t, J = 7.8 Hz, 1H), 7.08 (d, J = 9.0 Hz, 2H), 3.24 (t, J = 5.1 Hz, 4H), 2.48 (t, J = 5.0 Hz, 4H), 2.24 (s, 3H).

[1505] 1313C NMR (126 MHz, DMSO-d6) δ 159.20 (d, J = 259.6 Hz), 150.56, 148.79 (d, J = 13.5 Hz), 147.91, 144.24, 142.42, 134.53, 134.49, 132.72, 131.95, 127.45, 126.31, 125.33, 125.30, 119.33 (d, J = 12.6 Hz), 115.40, 115.17, 113.43, 112.30, 100.67 (d, J = 15.7 Hz), 54.14, 47.39, 45.28.

[1506] HRMS (APCI): Calcd for C 25 H 21 FN4O [M + H] + = 413.1772; Found [M + H] + = 413.1776.

[1507] Preparation Example 214: 2-Fluoro-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzamide

[1508]

[1509] Ghaffar-Parkins catalyst (8 mg, 0.019 mmol) was added to a solution of 77 mg (0.186 mmol) of 2-fluoro-3-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzonitrile (Preparation Example 213) in a mixture of EtOH (4 mL) and H2O (2 mL). The reaction mixture was stirred at 80 °C for 23 h. The reaction mixture was cooled, filtered, and concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient 1:0 to 94:6) gave the compound as a white solid (63 mg, 79% yield).

[1510] 11H NMR (500 MHz, DMSO-d6) δ 8.96 (d, J = 2.0 Hz, 1H), 8.91 (ddd, J = 7.3, 7.3, 1.8 Hz, 1H), 8.73 (d, J = 3.2 Hz, 1H), 8.38 (d, J = 2.0 Hz, 1H), 7.85 (s, 1H), 7.72 (d, J = 9.0 Hz, 2H), 7.67 (s, 1H), 7.62 (ddd, J = 8.7, 6.8, 1.9 Hz, 1H), 7.45 (dd, J = 7.7, 7.7 Hz, 1H), 7.09 (d, J = 9.0 Hz, 2H), 3.26 - 3.22 (m, 4H), 2.50 - 2.46 (m, 4H), 2.25 (s, 3H).

[1511] 13 13C NMR (126 MHz, DMSO) δ 164.94, 157.14, 155.13, 150.52, 148.17, 148.05, 147.82, 144.05, 142.94, 132.46, 131.24, 131.21, 128.49, 128.46, 127.43, 126.47, 124.55, 124.43, 123.88, 123.85, 118.59, 118.47, 115.24, 115.19, 113.57, 54.14, 47.42, 45.28.

[1512] HRMS (APCI): Calculated for C 25 H 23 FN4O2 [M + H] + = 431.1878; Found [M + H] + = 431.1882.

[1513] Preparation Example 215: 6-Chloro-3-(1,3-dimethyl-1H-pyrazol-4-yl)furo[3,2-b]pyridine

[1514]

[1515] Using 100 mg (0.430 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5) and 124 mg (0.559 mmol) of 1,3-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole, the compound was prepared by the general procedure A; the reaction time was 3 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:1) gave the compound as a white solid (67 mg, 63% yield).

[1516] 1H NMR (500 MHz, CDCl3) δ 8.56 (d, J = 2.0 Hz, 1H), 8.29 (s, 1H), 7.94 (s, 1H), 7.79 (d, J = 2.0 Hz, 1H), 3.92 (s, 3H), 2.44 (s, 3H).

[1517] 13 13C NMR (126 MHz, CDCl3) δ 147.71, 146.02, 144.99, 144.81, 143.82, 130.54, 127.77, 118.66, 115.06, 108.54, 38.92, 24.97, 13.92.

[1518] HRMS (APCI): Calcd for C 12 H 10 ClN3O [M+H] + = 248.0585; Found [M+H] + = 248.0588.

[1519] Preparation Example 216: 1-{4-[3-(1,3-Dimethyl-1H-pyrazol-4-yl)furo[3,2-b]pyridin-6- yl]phenyl}-4-methylpiperazine

[1520]

[1521] Using 50 mg (0.202 mmol) of 6-chloro-3-(1,3-dimethyl-1H-pyrazol-4-yl)furo[3,2-b]pyridine (Preparation Example 215) and 79 mg (0.263 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 3 h; flash chromatography (DCM / MeOH, gradient from 1:0 to 9:1) gave the compound as a white solid (57 mg, 73% yield).

[1522] 1 1H NMR (500 MHz, CDCl3) δ 8.83 (d, J = 1.9 Hz, 1H), 8.35 (s, 1H), 7.95 (s, 1H), 7.90 (d, J = 1.9 Hz, 1H), 7.59 - 7.54 (m, 2H), 7.07 - 7.02 (m, 2H), 3.94 (s, 3H), 3.44 - 3.30 (m, 4H), 2.81 - 2.64 (m, 4H), 2.51 - 2.40 (m, 6H).

[1523] 1313C NMR (126 MHz, CDCl3) δ 150.85, 148.59, 146.09, 144.82, 143.23, 133.19, 130.47, 129.46, 128.36, 116.61, 115.97, 114.95, 109.12, 54.92, 48.51, 45.90, 38.91, 13.97。

[1524] HRMS (APCI): Calcd for C 32 H 25 N5O [M+H] + = 388.2132; Found [M+H] + = 388.2135。

[1525] Preparation Example 217: 3-(6-Chlorofuro[3,2-b]pyridin-3-yl)-5-fluorobenzonitrile

[1526]

[1527] SPhos Pd G3 (6.7 mg, 0.0086 mmol) was added to a degassed mixture of 200 mg (0.860 mmol) of 3-bromo-6-chlorofuro[3,2-b]pyridine (Preparation Example 5), 170 mg (1.03 mmol) of (3-cyano-5-fluorophenyl)boronic acid and 366 mg of K3PO4 (1.72 mmol) in DMF (10.0 mL). The reaction mixture was stirred at 150 °C for 5 h, cooled to ambient temperature, diluted with EtOAc (30 mL), filtered and reduced in vacuo; flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 25:1) gave the title compound as a white solid (51 mg, 22% yield).

[1528] 1 1H NMR (500 MHz, CDCl3) δ 8.65 (d, J = 2.0 Hz, 1H), 8.24 - 8.20 (m, 2H), 8.14 (ddd, J = 9.6, 2.4, 1.5 Hz, 1H), 7.88 (d, J = 2.0 Hz, 1H), 7.35 (ddd, J = 7.8, 2.4, 1.3 Hz, 1H).

[1529] 1313C NMR (126 MHz, CDCl3) δ 162.69 (d, J = 250.4 Hz), 148.65, 146.54, 145.94, 143.36, 133.96 (d, J = 9.2 Hz), 128.62, 126.54 (d, J = 3.5 Hz), 119.32, 119.17 (d, J = 2.4 Hz), 118.78 (d, J = 22.9 Hz), 118.28 (d, J = 24.9 Hz), 117.64 (d, J = 3.5 Hz), 114.60 (d, J = 10.1 Hz).

[1530] HRMS (APCI): Calcd for C 14 H6ClFN2O [M + H] + = 273.0225; Found [M + H] + = 273.0227.

[1531] Preparation Example 218: 3-Fluoro-5-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3- yl)benzonitrile

[1532]

[1533] Using 50 mg (0.183 mmol) of 3-(6-chlorofuro[3,2-b]pyridin-3-yl)-5-fluorobenzonitrile (Preparation Example 217) and 72 mg (0.238 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 3 h; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a white solid (54 mg, 69% yield).

[1534] 1 1H NMR (500 MHz, CDCl3) δ 8.89 (d, J = 1.9 Hz, 1H), 8.28 (t, J = 1.3 Hz, 1H), 8.23 - 8.18 (m, 2H), 7.95 (d, J = 1.9 Hz, 1H), 7.59 - 7.55 (m, 2H), 7.33 (ddd, J = 7.8, 2.4, 1.3 Hz, 1H), 7.08 - 7.03 (m, 2H), 3.38 - 3.30 (m, 4H), 2.69 - 2.60 (m, 4H), 2.40 (s, 3H).

[1535] 1313C NMR (126 MHz, CDCl3) δ 162.70 (d, J = 250.2 Hz), 151.24, 149.60, 145.69 (d, J = 21.9 Hz), 143.19, 136.31, 134.72 (d, J = 9.2 Hz), 134.01, 128.53, 128.35, 126.53 (d, J = 3.2 Hz), 119.10 (d, J = 2.4 Hz), 118.76 (d, J = 22.8 Hz), 117.92 (d, J = 24.9 Hz), 117.78, 116.37 (d, J = 13.0 Hz), 114.46 (d, J = 10.1 Hz), 55.05, 48.60, 46.14。

[1536] HRMS (APCI): Calcd for C 25 H 21 FN4O [M + H] + = 413.1772; Found [M + H] + = 413.1776。

[1537] Preparation Example 219: 3-Fluoro-5-{6-[4-(4-methylpiperazin-1-yl)phenyl]furo[3,2-b]pyridin-3- yl}benzamide

[1538]

[1539] To a solution of Ghaffar-Parkins catalyst (0.5 mg, 0.0012 mmol) in a mixture of 23 mg (0.056 mmol) of 3-fluoro-5-(6-(4-(4-methylpiperazin-1-yl)phenyl)furo[3,2-b]pyridin-3-yl)benzonitrile (Preparation Example 218) in EtOH (1.0 mL) and H2O (0.5 mL) was added. The reaction mixture was stirred at 80 °C for 18 h. The reaction mixture was cooled, filtered, and concentrated in vacuo. Flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a white solid (19 mg, 79% yield).

[1540] 1 1H NMR (500 MHz, DMSO) δ 8.99 (d, J = 1.9 Hz, 1H), 8.95 (s, 1H), 8.56 (t, J = 1.4 Hz, 1H), 8.38 - 8.33 (m, 2H), 8.08 (br s, 1H), 7.73 - 7.69 (m, 2H), 7.67 - 7.63 (m, 1H), 7.58 (br s, 1H), 7.10 - 7.06 (m, 2H), 3.25 - 3.21 (m, 4H), 2.49 - 2.45 (m, 4H), 2.24 (s, 3H).

[1541] 13 C NMR(126MHz, DMSO) δ 166.54, 162.08(d, J = 243.4Hz), 150.80, 148.92, 147.70, 144.52, 142.78, 137.16(d, J = 7.3Hz), 132.80(d, J = 9.0Hz), 132.58, 127.75, 126.69, 121.76(d, J = 2.2Hz), 118.62(d, J = 2.5Hz), 115.75, 115.69, 115.50, 112.95(d, J = 22.8Hz), 54.45, 47.62, 45.73。

[1542] HRMS(APCI): Calculated for C 25 H 23 FN4O2 [M + H] + = 431.1878; Found [M + H] + = 431.1881。

[1543] Preparation Example 220: 5-Chloro-2-(pyridin-4-yl)ethynylpyridin-3-yl acetate

[1544]

[1545] To a degassed solution of 5-chloro-2-iodopyridine-3-yl acetate (Preparation Example 192; 600 mg, 2.017 mmol) in THF (4 mL) and TEA (2.4 mL) was added 4-ethynylpyridine (270 mg, 2.622 mmol), PdCl2(PPh3)2 (43 mg, 0.061 mmol), and CuI (23 mg, 0.121 mmol). The resulting mixture was stirred at 45 °C for 120 minutes. The solvent was evaporated and the residue was purified by flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:1). A brown oil product (331 mg, 60% yield) was obtained.

[1546] 1 H NMR(500MHz, chloroform-d) δ 8.65(d, J = 5.3Hz, 2H), 8.49(d, J = 2.1Hz, 1H), 7.60(d, J = 2.1Hz, 1H), 7.43 - 7.38(m, 2H), 2.40(s, 3H)。

[1547] 1313C NMR (126 MHz, CDCl3) δ 167.88, 150.73, 150.11, 150.08, 148.91, 146.72, 146.27, 134.60, 132.30, 132.25, 132.22, 130.56, 130.06, 125.77, 118.73, 105.81, 91.92, 87.51, 20.93。

[1548] HRMS (APCI): Calculated for C 14 H9ClN2O2 [M + H] + = 273.0425; Found [M + H] + = 273.0427.

[1549] Preparation Example 221: 6-Chloro-3-iodo-2-(pyridin-4-yl)furo[3,2-b]pyridine

[1550]

[1551] To a solution of 5-chloro-2-(pyridin-4-ylethynyl)pyridin-3-yl acetate (Preparation Example 220; 300 mg, 1.100 mmol) in MeOH (10 mL) was added a solution of iodine (838 mg, 3.300 mmol) in MeOH (10 mL) and CsHCO3 (640 mg, 3.300 mmol). The resulting mixture was stirred at 40 °C for 2 h in a flask wrapped with aluminum foil. A solution of Na2S2O3 (1.092 g, 4.401 mmol) in H2O (3 mL) was added, and the mixture was concentrated to dryness in vacuo. The residue was purified by column chromatography (cyclohexane / EtOAc, gradient from 1:0 to 1:1) to give a pale yellow solid product (167 mg, 33% yield).

[1552] 1 1H NMR (500 MHz, chloroform-d) δ 8.81 (d, J = 5.3 Hz, 2H), 8.63 (d, J = 2.0 Hz, 1H), 8.22 - 8.10 (m, 2H), 7.85 (d, J = 1.9 Hz, 1H).

[1553] 13 13C NMR (126 MHz, CDCl3) δ 154.11, 150.56, 147.64, 146.94, 146.80, 136.53, 130.01, 120.89, 118.97, 77.16, 67.73。

[1554] HRMS (APCI): Calculated for C 12 H6ClIN2O [M + H] += 356.9286; Measured value [M+H] + = 356.9289.

[1555] Preparation Example 222: 6-Chloro-3-phenyl-2-(pyridin-4-yl)furo[3,2-b]pyridine

[1556]

[1557] Using 100 mg (0.280 mmol) of 6-chloro-3-iodo-2-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 221) and 45 mg (0.365 mmol) of phenylboronic acid, the compound was prepared by General Procedure A; the reaction time was 2 hours; flash chromatography (cyclohexane / EtOAc, gradient from 1:0 to 2:1) gave a pale yellow solid compound (63 mg, 73% yield).

[1558] 1 H NMR (500 MHz, chloroform-d) δ 8.65 - 8.60 (m, 2H), 8.58 (d, J = 2.1 Hz, 1H), 7.88 (d, J = 2.0 Hz, 1H), 7.60 - 7.56 (m, 4H), 7.55 - 7.48 (m, 3H).

[1559] 13 C NMR (126 MHz, CDCl3) δ 151.91, 150.33, 147.44, 146.47, 146.29, 137.27, 129.93, 129.56, 129.43, 129.09, 128.82, 121.64, 120.68, 118.66.

[1560] HRMS (APCI): Calculated for C 18 H 11 ClN2O [M+H] + = 307.0633; Measured value [M+H] + = 307.0635.

[1561] Preparation Example 223: 1-Methyl-4-{4-[3-phenyl-2-(pyridin-4-yl)furo[3,2-b]pyridin-6- yl]phenyl}piperazine

[1562]

[1563] Using 50 mg (0.163 mmol) of 6-chloro-3-phenyl-2-(pyridin-4-yl)furo[3,2-b]pyridine (Preparation Example 222) and 59 mg (0.196 mmol) of 1-methyl-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperazine, the compound was prepared by General Procedure B; the reaction time was 3 hours; flash chromatography (DCM / MeOH, gradient 1:0 to 9:1) gave the compound as a pale yellow solid (54 mg, 74% yield).

[1564] 1 H NMR (500 MHz, chloroform-d) δ 8.85 (d, J = 1.9 Hz, 1H), 8.60 (d, J = 6.2 Hz, 2H), 7.97 (d, J = 1.9 Hz, 1H), 7.71 - 7.44 (m, 9H), 7.05 (d, J = 8.8 Hz, 2H), 3.32 (t, J = 5.0 Hz, 4H), 2.63 (t, J = 4.9 Hz, 4H), 2.39 (s, 3H).

[1565] 13 C NMR (126 MHz, CDCl3) δ 151.28, 151.01, 150.40, 148.42, 146.36, 146.13, 137.65, 134.45, 130.33, 130.01, 129.37, 128.80, 128.69, 128.30, 121.78, 120.58, 116.35, 115.65, 55.12, 48.69, 46.24.

[1566] HRMS (APCI): Calcd for C 29 H 26 N4O [M + H] + = 447.2179; Found [M + H] + = 447.2178.

[1567] Preparation Example 224: 5-Chloro-2-(cyclohexyl)ethynylpyridin-3-yl acetate

[1568]

[1569] To a degassed solution of 5-chloro-2-iodopyridine-3-yl acetate (Preparation Example 192; 600 mg, 2.017 mmol) in THF (4 mL) and TEA (2.4 mL) was added cyclohexylacetylene (284 mg, 2.622 mmol), PdCl2(PPh3)2 (43 mg, 0.061 mmol), and CuI (23 mg, 0.121 mmol). The resulting mixture was stirred at 45 °C for 2 h. The solvent was evaporated and the residue was purified by flash chromatography (cyclohexane / EtOAc, gradient 1:0 to 9:1). A brown oil product (422 mg, 75% yield) was obtained.

[1570] 1 1H NMR (500 MHz, chloroform-d) δ 8.39 (d, J = 2.1 Hz, 1H), 7.47 (d, J = 2.2 Hz, 1H), 2.67 (tt, J = 9.0, 3.8 Hz, 1H), 2.35 (s, 3H), 1.94 - 1.83 (m, 2H), 1.76 (tdd, J = 11.9, 5.6, 2.1 Hz, 2H), 1.56 (tdd, J = 16.5, 7.7, 2.9 Hz, 3H), 1.45 - 1.31 (m, 3H).

[1571] 13 13C NMR (126 MHz, CDCl3) δ 168.01, 148.38, 146.16, 136.37, 130.39, 130.12, 101.68, 75.48, 32.33, 31.11, 29.85, 25.94, 25.90, 24.85, 20.92.

[1572] HRMS (APCI): Calcd for C 15 H 16 ClNO2 [M + H] + = 278.0942; Found [M + H] + = 278.0945.

[1573] Preparation Example 225: 6-Chloro-2-cyclohexyl-3-iodofuro[3,2-b]pyridine

[1574]

[1575] To a solution of 5-chloro-2-(cyclohexylethynyl)pyridin-3-yl acetate (Preparation Example 224; 384 mg, 1.383 mmol) in MeOH (10 mL) was added a solution of iodine (1.052 g, 3.4148 mmol) in MeOH (10 mL) and CsHCO3 (804 mg, 4.148 mmol). The resulting mixture was stirred at 40 °C for 120 minutes in a flask wrapped with aluminum foil. A solution of Na2S2O3 (1.372 g, 5.530 mmol) in H2O (4 mL) was added, and the mixture was concentrated to dryness in vacuo. The residue was purified by column chromatography (cyclohexane) to give a pale yellow oil product (186 mg, 37% yield).

[1576] 1 H NMR (500 MHz, chloroform-d) δ 8.51 (d, J = 2.0 Hz, 1H), 7.67 (d, J = 1.9 Hz, 1H), 3.11 - 2.98 (m, 1H), 1.90 (tt, J = 13.2, 3.8 Hz, 4H), 1.78 (dtt, J = 11.5, 3.3, 1.6 Hz, 1H), 1.69 (qd, J = 13.5, 12.8, 3.7 Hz, 2H), 1.49 - 1.26 (m, 4H).

[1577] 13 C NMR (126 MHz, CDCl3) δ 167.40, 147.44, 146.76, 145.30, 127.63, 118.24, 77.16, 63.33, 38.59, 30.52, 26.15, 25.82.

[1578] HRMS (APCI): Calcd for C 13 H 13 ClINO [M + H] + = 361.9803; Found [M + H] + = 361.9807.

[1579] Preparation Example 226: 6-Chloro-2-cyclohexyl-3-phenylfuro[3,2-b]pyridine

[1580]

[1581] The compound was prepared by General Procedure A using 100 mg (0.277 mmol) of 6-chloro-2-cyclohexyl-3-iodofuro[3,2-b]pyridine (Preparation Example 225) and 44 mg (0.360 mmol) of phenylboronic acid; the reaction time was 2 hours; flash chromatography (cyclohexane) gave a pale yellow solid compound (80 mg, 93% yield).

[1582] 1 1H NMR (500 MHz, chloroform-d) δ 8.49 (d, J = 2.0 Hz, 1H), 7.72 (d, J = 2.0 Hz, 1H), 7.64 - 7.59 (m, 2H), 7.50 (t, J = 7.7 Hz, 2H), 7.43 - 7.36 (m, 1H), 3.06 (tt, J = 11.8, 3.5 Hz, 1H), 1.90 (dddd, J = 18.7, 9.2, 4.8, 2.4 Hz, 5H), 1.84 - 1.75 (m, 4H), 1.40 - 1.32 (m, 3H).

[1583] 13 13C NMR (126 MHz, CDCl3) δ 164.39, 146.75, 146.62, 144.64, 130.77, 129.91, 129.49, 128.95, 128.02, 127.70, 126.60, 117.82, 116.05, 37.00, 31.44, 27.09, 26.25, 25.90.

[1584] HRMS (APCI): Calcd for C 19 H 18 ClNO [M + H] + = 312.1150; Found [M + H] + = 312.1152.

[1585] Preparation Example 227: 1-(4-{2-Cyclohexyl-3-phenylfuro[3,2-b]pyridin-6-yl}phenyl)-4-methylpiperazine piperazine [...

Claims

1. A compound of general formula I wherein: R 2 selected from H, C1-C4 alkyl, CF3, C5-C7 cycloalkyl, phenyl and pyridyl; Y is selected from a bond, O, S, SO2, -C≡C-, NR 8 and CR 8 R 8 ; R 3 selected from the group consisting of: - C6-C14 aryl, - a 3- to 10-membered heteroaryl containing at least one heteroatom selected from S, O, N; provided that the heteroaryl is not unsubstituted quinoline or unsubstituted isoquinoline; Wherein, each of the listed substituents can optionally be substituted by at least one substituent independently selected from the following: C1-C4 alkyl, C6-C10 aryl, 3- to 7-membered heteroaryl containing at least one heteroatom selected from S, O, N, 3- to 7-membered cycloheteroalkyl containing at least one heteroatom selected from S, O, N, 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- to 6-membered heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 haloalkyl), S(C5-C6 aryl or 5- to 6-membered 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- to 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 alkylene)-CHO, -CHO, -COOH, -(C1-C4 alkylene)-COOH, -CONH2, -(C1-C4 alkylene)-CONH2, -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- to 6-membered heteroaryl), -(C1-C4 alkylene)-CO(C5-C6 aryl or 5- to 6-membered heteroaryl), (C1-C4 alkyl)-SO2-, (C1-C4 alkyl)-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-SO-, (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 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)2N-CO-, (C1-C4 alkyl)2N-CO-(C1-C4 alkylene)-, NH2-SO2-, NH2-SO2-(C1-C4-alkylene)-, (C6-C10 aryl)-NH-SO2-, (C6-C10 aryl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-NH-SO2-, (C1-C4 alkyl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)2N-SO2-, (C1-C4 alkyl)2N-SO2-(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-, (C1-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-, NH2-CO-NH-, (C1-C4 alkyl)-NH-CO-NH-, (C1-C4 alkyl)2N-CO-NH-, NH2-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)2N-CO-N(C1-C4 alkyl)-, NH2-S(O)2-NH-, (C1-C4 alkyl)-NH-S(O)2-NH-, (C1-C4 alkyl)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-; Z is selected from a bond, O, S, SO2, NR 8 and CR 8 R 8 ; R 6 selected from the group consisting of: - C6-C14 aryl, - a 3- to 10-membered heteroaryl containing at least one heteroatom selected from S, O, N, - C3-C8 cycloalkyl, preferably C4-C7 cycloalkyl, - a 3- to 8-membered cycloheteroalkyl containing 1 to 2 heteroatoms selected from S, O, N, - C3-C8 cycloalkenyl, - a 3- to 8-membered cycloheteroalkenyl containing 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkyl-(C6-C14) aryl, -(3- to 8-membered) cycloheteroalkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkenyl-(C6-C14) aryl, -(3- to 8-membered) cycloheteroalkenyl-(C6-C14) aryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkyl-(3- to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3- to 8-membered) cycloheteroalkyl-(3- to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkenyl-(3- to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3- to 8-membered) cycloheteroalkenyl-(3- to 10-membered) heteroaryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkyl-(C1-C4) alkyl-(C6-C14) aryl, -(3- to 8-membered) cycloheteroalkyl-(C1-C4) alkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkenyl-(C1-C4) alkyl-(C6-C14) aryl, -(3- to 8-membered) cycloheteroalkenyl-(C1-C4) alkyl-(C6-C14) aryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkyl-(C1-C4) alkyl-(3- to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3- to 8-membered) cycloheteroalkyl-(C1-C4) alkyl-(3- to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkenyl-(C1-C4) alkyl-(3- to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3 to 8-membered) cycloheteroalkenyl-(C1-C4)alkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl, -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkenyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl, -(3 to 8-membered) cycloheteroalkenyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkenyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3 to 8-membered) cycloheteroalkenyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkenyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(5 to 10-membered) heteroalkyl-C6-C14 aryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(5 to 10-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, Wherein, each of the listed substituents can be unsubstituted or substituted by at least one substituent independently selected from the following: C1-C4 alkyl, C6-C10 aryl, 3- to 7-membered heteroaryl containing at least one heteroatom selected from S, O, N, 3- to 7-membered cycloheteroalkyl containing at least one heteroatom selected from S, O, N, 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- to 6-membered heteroaryl), SH, S(C1-C4 alkyl), S(C3-C7 cycloalkyl), S(C1-C4 haloalkyl), S(C5-C6 aryl or 5- to 6-membered 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- to 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 alkylene)-CHO, -CHO, -COOH, -(C1-C4 alkylene)-COOH, -CONH2, -(C1-C4 alkylene)-CONH2, -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- to 6-membered heteroaryl), -(C1-C4 alkylene)-CO(C5-C6 aryl or 5- to 6-membered heteroaryl), (C1-C4 alkyl)-SO2-, (C1-C4 alkyl)-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-SO-, (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 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)2N-CO-, (C1-C4 alkyl)2N-CO-(C1-C4 alkylene)-, NH2-SO2-, NH2-SO2-(C1-C4-alkylene)-, (C6-C10 aryl)-NH-SO2-, (C6-C10 aryl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)-NH-SO2-, (C1-C4 alkyl)-NH-SO2-(C1-C4 alkylene)-, (C1-C4 alkyl)2N-SO2-, (C1-C4 alkyl)2N-SO2-(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-, (C1-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-, NH2-CO-NH-, (C1-C4 alkyl)-NH-CO-NH-, (C1-C4 alkyl)2N-CO-NH-, NH2-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)-NH-CO-N(C1-C4 alkyl)-, (C1-C4 alkyl)2N-CO-N(C1-C4 alkyl)-, NH2-S(O)2-NH-, (C1-C4 alkyl)-NH-S(O)2-NH-, (C1-C4 alkyl)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-; R 7 selected from H, C1-C4 alkyl, and CF3; R 8 independently selected from H and C1-C4 alkyl groups.

2. The compound of general formula I according to claim 1, wherein, R 2 selected from H, methyl, ethyl, propyl, isopropyl, cyclohexyl, phenyl and pyridyl; and / or R 7 Selected from H, methyl, ethyl, propyl, and isopropyl.

3. The compound of general formula I according to claim 1 or 2, wherein, Y is selected from a bond, -C≡C-, NR 8 or CR 8 R 8 ; and / or Z is selected from a bond, NR 8 or CR 8 R 8 ; More preferably, Y is a bond and / or Z is a bond.

4. A compound of general formula I according to any one of claims 1 to 3, wherein, R 3 selected from phenyl and 5- to 6-membered heteroaryl containing one or two heteroatoms selected from N, O, and S; wherein the phenyl or 5- to 6-membered heteroaryl is unsubstituted or substituted.

5. A compound of general formula I according to any one of claims 1 to 4, wherein, R 6 selected from the group consisting of: -C6-C14 aryl, -3 to 10-membered heteroaryl containing at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkyl-(C6-C14) aryl, -(3 to 8-membered) cycloheteroalkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3 to 8-membered) cycloheteroalkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkyl-(C1-C4) alkyl-(C6-C14) aryl, -(3 to 8-membered) cycloheteroalkyl-(C1-C4) alkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkyl-(C1-C4) alkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3 to 8-membered) cycloheteroalkyl-(C1-C4) alkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl, -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(C6-C14) aryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(C3-C8) cycloalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(3 to 8-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(5 to 10-membered) heteroalkyl-C6-C14 aryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, -(5 to 10-membered) heteroalkyl-(3 to 10-membered) heteroaryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, N, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, wherein each of the listed substituents can be unsubstituted or substituted.

6. The compound according to any one of claims 1 to 5, wherein, R 6 selected from the group consisting of: -phenyl, -5 to 6-membered heteroaryl containing at least one heteroatom selected from S, O, N, -(6-membered) cycloheteroalkyl-phenyl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from O, N and is bonded to the phenyl through an N atom, -(6-membered) cycloheteroalkyl-(5 to 6-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from O, N and is bonded to the heteroaryl through an N atom, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(6-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-phenyl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from O, N and is bonded to the heteroalkyl through an N atom, -(6-membered) cycloheteroalkyl-(1 to 4-membered) heteroalkyl-(5 to 6-membered) heteroaryl, wherein the cycloheteroalkyl contains 1 to 2 heteroatoms selected from O, N and is bonded to the heteroalkyl through an N atom, and wherein the heteroaryl contains at least one heteroatom selected from S, O, N, -(5 to 10-membered) heteroalkyl-phenyl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from O and N and is bonded to the phenyl through an N atom, -(5 to 10-membered) heteroalkyl-(5 to 6-membered) heteroaryl, wherein the heteroalkyl contains 1 to 2 heteroatoms selected from S, O, and N, and wherein the heteroaryl contains at least one heteroatom selected from O and N and is bonded to the heteroalkyl through an N atom, wherein each of the listed substituents can be unsubstituted or substituted.

7. A compound of general formula I according to any one of claims 1 to 6, wherein, R 6 The substituents listed are unsubstituted or further substituted by at least one substituent, preferably by one substituent, wherein the at least one substituent is independently selected from C1-C4 alkyl, halogen, OH, HO-C1-C4 alkyl, O(C1-C4 alkyl), O(C5-C6 aryl or heteroaryl), SH, S(C1-C4 alkyl), S(C5-C6 aryl or heteroaryl), CF3, C2F5, OCF3, OC2F5, amino (NH2), C1-C4 alkylamino, di(C1-C4 alkyl)amino, and more preferably, the at least one substituent is selected from C1-C4 alkyl.

8. The compound of formula I according to claim 1, which is selected from the group consisting of the following compounds:

9. Use of the compound of formula I according to any one of claims 1 to 8 as a medicament.

10. Use of the compound of formula I according to any one of claims 1 to 8 in the treatment of FLT3-related diseases, DDR-related diseases, and MAP4K-related diseases.

11. Use of a compound of general formula I according to claim 9 or 10, wherein, The compound is used for the treatment of cancer, inflammatory diseases, autoimmune diseases, neurodegenerative diseases, or metabolic diseases.

12. Use of a compound of general formula I according to claim 9 or 10, wherein, The compound is used for the treatment of leukemia, rheumatoid arthritis, autoimmune hepatitis, peripheral neuropathic pain, non-small cell lung cancer (NSCLC), ovarian cancer, glioblastoma, breast cancer, lung cancer, lung adenocarcinoma, pancreatic cancer, prostate cancer, brain cancer, colorectal cancer, liver cancer, hepatocellular carcinoma, squamous cell carcinoma, periodontitis, pulmonary fibrosis, obesity, insulin resistance, obesity-induced hyperinsulinemia, atherosclerosis, or Alzheimer's disease.

13. A pharmaceutical preparation comprising at least one compound of formula I according to any one of claims 1 to 8, and at least one pharmaceutically acceptable excipient selected from pharmaceutically acceptable solvents, fillers, and binders.

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