1,2-dicarboxamide compounds as kinase inhibitors

Abstract

The present invention relates to quinoline compounds of Formula (I); pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, N-oxides or combination thereof, wherein 'X' ring A, ring B, R1, R2, R3, R4, R5, R6, R7, R8, 'm' and 'n' are as defined herein. The present invention also relates to quinoline compounds that modulate cellular activities like proliferation, differentiation, adhesion, migration and apoptosis by modulating protein kinase enzymatic activity. In particular the invention relates to compounds which inhibit, regulate, and / or modulate tyrosine kinases such as FLT1 (VEGFR1), FLT4 (VEGFR3), KDR (VEGFR2), MET (C-Met), MERTK (c-Mer), RET, AXL, TEK (TIE 2) and EGFR. The present disclosure relates to quinoline compounds for use in modulating kinase enzymatic activity and accordingly modulating kinase-dependent associated diseases and conditions such as cancers like Thyroid carcinoma, Ovarian carcinoma, Pancreatic carcinoma, Prostatic carcinoma, Renal cell carcinoma, Hepatocellular carcinoma, Breast carcinoma, Colorectal carcinoma, Oral squamous cell carcinoma, Colorectal, Lung adenocarcinoma or Endometrial cancer.

Description

[0001] 1,2-DICARBOXAMIDE COMPOUNDS AS KINASE INHIBITORS This application claims the benefit of Indian provisional application no. 202441043235 filed on 04thJune 2024 which is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION The present disclosure relates to 1,2-dicarboxamide compounds that modulate cellular activities like proliferation, differentiation, adhesion, migration and apoptosis by modulating protein kinase enzymatic activity. In particular the present invention relates to compounds which inhibit, regulate, and / or modulate tyrosine kinases such as FLT1 (VEGFR1), FLT4 (VEGFR3), KDR (VEGFR2), MET (c-MET), MERTK (c-Mer), RET, AXL, TEK (TIE 2) and EGFR. The present disclosure relates to 1,2-dicarboxamide compounds for use in modulating kinase enzymatic activity and accordingly modulating kinase-dependent associated diseases and conditions such as cancers like Thyroid carcinoma, Ovarian carcinoma, Pancreatic carcinoma, Prostatic carcinoma, Renal cell carcinoma, Hepatocellular carcinoma, Breast carcinoma, Colorectal carcinoma, Oral squamous cell carcinoma, Colorectal, Lung adenocarcinoma or Endometrial cancer. BACKGROUND OF THE INVENTION Protein tyrosine kinases (PTKs) are enzymes that catalyze the transfer of the- phosphate group of ATP to tyrosine residues of protein substrates. The activity of PTKs is controlled in a complex manner by posttranslational modifications and by inter- and intramolecular complex formations (Hubbard et al., 1998. J Biol Chem., 273(20):11987-90; Hubbard and Till,2000. Annu Rev Biochem., 69:373–398). PTKs have been implicated in the regulation of a variety of biological responses such as cell proliferation, migration, differentiation, and survival. They have been demonstrated to play important roles in the development of many disease states, including immunodeficiency, atherosclerosis, psoriasis, osteoporosis, diabetes, and cancer. Enhanced activity of PTKs has been implicated in a variety of malignant and nonmalignant proliferative diseases. In addition, PTKs play a central role in the regulation of cells of the immune system. PTK inhibitors can thus impact a wide variety of oncologic and immunologic disorders. Of the many different cellular functions in which the activity of protein kinases is known to be required, some processes represent attractive targets for therapeutic intervention for certain disease states. Two examples are angiogenesis and cell-cycle control, in which protein kinases play a pivotal role; these processes are essential for the growth of solid tumors as well as for other diseases. Angiogenesis is the process of new capillaries forming out of preexisting blood vessels in your body. It’s normally a helpful, important process that supports wound healing and supplies oxygen-rich blood to organs and tissues. If required, the vascular system has the potential to generate new capillary networks in order to maintain the proper functioning of tissues and organs. In the adult, however, angiogenesis is fairly limited, occurring only in the process of wound healing and neovascularization of the endometrium during menstruation. (Merenmies et al., 1997. Cell Growth & Differentiation, 8, 3-10). On the other hand, unwanted angiogenesis is a hallmark of several diseases, such as retinopathies, psoriasis, rheumatoid arthritis, age-related macular degeneration (AMD), and cancer (solid tumors). (Folkman, 1995. Nature Med., 1(1), 27-31). In particular, people with cancer, angiogenesis supports tumor growth and spread by feeding tumors with oxygen and nutrients. Protein kinases which are involved in the angiogenic process include three members of the growth factor receptor tyrosine kinase family: VEGF-R2 (vascular endothelial growth factor receptor 2, also known as KDR (kinase insert domain receptor). FGF-R (fibroblast growth factor receptor); and TEK (Tie-2). VEGF-R2, which is expressed only on endothelial cells, binds the potent angiogenic growth factor VEGF and mediates the subsequent signal transduction through activation of its intracellular kinase activity. Thus, it is expected that direct inhibition of the kinase activity of VEGF-R2 will result in the reduction of angiogenesis (Strawn et al., 1996. Cancer Research, 56(15), 3540-3545). TEK (TIE2) receptor tyrosine kinase is expressed in vascular endothelial cells, tumor- associated macrophages, and tumor cells and has been a major focus of research in therapies targeting the tumor microenvironment. The most extensively studied Tie2 ligands are Angiopoietin 1 and 2 (Ang1, Ang2). Ang1 plays a critical role in vessel maturation, endothelial cell migration, and survival. Ang2, depending on the context, may function to disrupt connections between the endothelial cells and perivascular cells, promoting vascular regression. However, in the presence of VEGF-A, Ang2 instead promotes angiogenesis. TIE 2-expressing macrophages play a critical role in both tumor angiogenesis and the dissemination of tumor cells from the primary tumor to secondary sites. Therefore, Ang-TIE 2 signaling functions as an angiogenic switch during tumor progression and metastasis (Duran et al., 2021. Cancers (Basel)., 13(22): 5730). Only a small number of studies have reported TIE2 expression in tumor cells of both an epithelial and a non-epithelial origin. Kukk et al., (1997) investigated Tie2 signaling in hematopoietic progenitors and leukemic cells. High Tie2 expression has also been shown to be a prognostic factor for poor survival and increased metastases in several cancers. In high grade serous ovarian cancer, high TIE2 expression predicted a shorter overall survival and distal omental metastasis. TIE2 expression was also increased in metastatic lesions compared with primary tumors (PLoS ONE.2020;15: e0241484). In gastric cancer, an evaluation of TIE 2 expression through immunohistochemistry found that TIE2 expression increased with increasing tumor grade, the presence of lymph node metastases, higher recurrence rates, and poor patient survival (Yang et al., 2018. Oncol. Lett., 15(5):8027–8033). c-MET receptor, which belongs to the receptor tyrosine kinase (RTK) family, plays essential roles in controlling a number of critical cellular processes such as cell proliferation, survival, motility, and morphogenesis (Birchmeier et al., 2003. Nat. Rev. Mol. Cell Biol., 4(12):915–925; Organ and Tsao, 2011. Ther. Adv. Med. Oncol., 2011.3(1 Suppl): S7– S19). Aberrant activation of c-MET can lead to both tumour growth and metastatic progression of cancer cells, making it an important drug target for cancer treatments (Benedetta and Donald, 2006. Clin. Cancer Res., 12(12):3657–3660; Joseph et al., 2009. Clin. Cancer Res., 15 (7):2207–2214). High c-MET expression is closely associated with poor prognosis in cancer patients. Studies have shown that abnormal activation of c-MET is critical for resistance to targeted therapies such as tyrosine kinase inhibitors and drugs that act against associated signalling pathways. Therefore, as abnormal c-MET function can increase the difficulty associated with tumour treatment, understanding its role in cancer is extremely important (Zhu et al., 2016. J Cell Sci.,129(22):4238–51; Caenepeel et al., 2017. Oncotarget., 8(11):17795–809). AXL is involved in various cellular processes including cell growth, proliferation, survival, apoptosis, and adhesion. Given this, the involvement of AXL in cancer progression is not unexpected (AXL as a Target in Breast Cancer Therapy. J. Oncol. 2020). It has been associated with different high-grade cancers and correlated with poor prognosis (Colavito S.A., 2020. J. Oncol., 14:5291952). Furthermore, higher levels of AXL expression are found in highly invasive cancer cell lines compared to less invasive cancer cell lines indicating an association with migration and invasiveness of cancer cells. It is a promising therapeutic target, and several inhibitors directed to AXL are currently in clinical trials. The understanding of AXL’s role in the development of resistance can lead to improved and new cancer therapeutic strategies (Martha et al., 2021. Cancers (Basel)., 13(7): 1521). Rearranged during transfection (RET) is the tyrosine kinase receptor that under normal circumstances binds ligand at the cell surface and mediates various essential roles in a variety of cellular processes such as proliferation, differentiation, survival, migration, and metabolism. RET plays a pivotal role in the development of both peripheral and central nervous systems. RET is expressed from early stages of embryogenesis and remains expressed throughout all life stages. Mutations either activating or inhibiting RET result in several aggressive diseases, namely cancer and Hirschsprung disease. However, the physiological ligand-dependent activation of RET receptor is important for the survival and maintenance of several neuronal populations, appetite, and weight gain control, thus providing an opportunity for the development of disease-modifying therapeutics against neurodegeneration and obesity (Mahato and Sidorova, 2020. Int. J. Mol. Sci.,21(19): 7108). Moreover, recent development of RET-specific kinase inhibitors contributed significantly to progress in the treatment of patients with RET-altered cancer. Epidermal growth factor receptor (EGFR) is a receptor tyrosine protein kinase, and a transmembrane protein in the ErbB receptor family. EGFR regulates proliferation, survival, adhesion, migration and differentiation of cells, which is hyperactivated or sustained in a variety of tumor cells, such as lung cancer cells, breast cancer cells, prostate cancer cells and the like. Abnormal activation of EGFR plays a key role in tumor transformation and growth. Blocking activation of EGFR has been clinically proven as one of the effective targeted therapies for treating cancer. EGFR downstream signalling is implicated in the development and progression of various cancers, including non-small cell lung cancer (NSCLC), breast cancer, head and neck cancer, colorectal cancer, pancreatic cancer, and glioblastoma. EGFR mutations or overexpression can drive cancer cell proliferation, survival, and metastasis by activating downstream signalling pathways like PI3K / AKT / mTOR, RAS / RAF / MEK / ERK, and others. Inhibiting the EGFR (Epidermal Growth Factor Receptor) downstream signalling pathway primarily prevents the cell from receiving external growth signals and can disrupt cellular processes like proliferation, survival, and differentiation. This can lead to a decrease in cell growth and even cell death in certain cases, making it a potential therapeutic target in cancer. WO2000042012A1 describes ω-carboxyaryl substituted diphenyl ureas as RAF kinase inhibitors; WO2001060814Al describes pyrrole substituted 2-indolinone protein kinase inhibitors; WO2001032651 A1 describes quinazoline derivatives as VEGF inhibitors; WO2002059110A1 describes pyrimidineamines as angiogenesis modulators; WO2004078746A2 describes 2-oxo-l,3,5-perhydrotriazapine derivatives useful in the treatment of hyper-proliferative, angiogenesis, and inflammatory disorders; WO 2005030140 A2 describes C-MET modulators and methods of use; WO2007075869 A2 describes bicyclic heteroaryl compounds; US5521184A describes pyrimidine derivatives and processes for the preparation thereof; US6762180B1 describes substituted indolines which inhibit receptor tyrosine kinases; US7253286B2 describes nitrogen-containing aromatic derivatives; WO2009137391A2 describes Benzene sulfonamide thiazole and oxazole compounds; WO2007109120A2 describes Imidazolothiazole compounds for the treatment of disease; US20030087907A1 describes Quinoline derivatives and quinazoline derivatives having azolyl group; WO2001002369 A2 describes indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use; WO2019148044 A1 describes quinoline compounds as AXL and TAM family receptor tyrosine kinase inhibitors. US11702425 B2 discloses Bicyclic compounds as kinase modulators in particular to treatment of Hepta Cellular Carcinoma (HCC) and compounds disclosed herein are having less inhibitory activity towards c-Kit, inhibition of c-Kit causes adverse effects such as myelosuppression (Galanis and Levis, 2015. Haematologica, 100(3): e77–e79). Based on these proof-of-principle results, still there is a need of development for clinically applicable multi-kinase inhibitors to provide significant benefits, in overcoming the challenge associated with lack of knowledge of the target specificity of multi-kinase inhibitors, to overcome the resistance developed in the existing therapies and to overcome the side effects associated with the existed therapies. SUMMARY OF THE INVENTION The present invention relates to the compound of the Formula (I): Formula (I) wherein, ‘X’ is selected from -O- or -S-; R1 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; or R1 and R2 together with the oxygen atoms to which they are attached to form a 6-12 membered heterocyclic ring; ring aryl or heteroaryl; R3 is selected from hydrogen, hydroxyl, halo, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro or amino; R4 and R5 are independently selected from hydrogen or C1-C6 alkyl or R4 and R5 are taken together with the carbon atom(s) to which they are attached to form substituted or unsubstituted C3-C10 cycloalkyl; wherein one or more substituents are independently selected from halogen or C1-C6 alkyl; R6 is selected form hydrogen, amino, hydroxyl, -O-Rb, halo, C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted aryl, C1-C6haloalkyl, C1-C6alkoxy, cycloalkyloxy, cyano, nitro, -C(O)-alkyl, -C(O)-O-alkyl or amino; wherein the substituents are independently selected from one or more amino, cyano, halo, C1-C6 haloalkyl, hydroxy, C1-C6 alkyl or C1- C6 alkoxy; R7 is hydrogen or C1-C6 alkyl; R8 is hydrogen or C1-C6 alkyl; ring is selected from C3-C6 cycloalkyl, C6-C12 aryl, C6-C12 arylalkyl, heteroaryl, or heterocyclyl; Ra is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; Rb is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; ‘---’ is an optional bond; ‘m’ is an integer selected from 0, 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, 2, 3, 4 or 5; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof. According to one embodiment, there is provided a compound of Formula (I), wherein ‘X’ is ‘O’ or “S’ According to another embodiment, there is provided a compound of Formula (I), , According to yet another embodiment, there is provided a compound of Formula (I), wherein R1 is selected from hydrogen, methyl, deutiromethyl, ethyl, isopropyl, tert-butyl, , , , , According to yet another embodiment, there is provided a compound of Formula (I), wherein R2is selected from hydrogen, methyl, deutiromethyl, ethyl, isopropyl, tert-butyl, According to yet another embodiment, there is provided a compound of Formula (I), wherein R3 is selected from, fluoro, chloro, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, cyano, amino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl, N-ethyl, N-propyl or N-acetyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R4 and R5 are hydrogen or methyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R4 and R5 taken together with the carbon atoms to which they are attached to form cycloalkyl; wherein the cycloalkyl is selected from , , , or . According to yet another embodiment, there is provided a compound of Formula (I), wherein ring A is selected from, , According to yet another embodiment, there is provided a compound of Formula (I), wherein R6 is selected from fluoro, chloro, methyl, ethyl, propyl, isopropyl, tert-butyl, methoxy, ethoxy, isopropoxy, tert-butoxy, cyano, amino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, N-methyl, N-ethyl, N-propyl or N-acetyl. Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (IA): Formula (IA) where in, ring A, ring B, R1, R2, R3, R4, R5, R6, R7, R8, ‘m’ and ‘n’ are as defined in compound Formula (I). Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (IB): Formula (IB) where in, ring A, R1, R2, R3, R4, R5, R6, R7, R8, ‘m’ and ‘n’ are as defined in compound Formula (I). Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (IC): Formula (IC) where in, R1, R2, R3, R4, R5, R6, R7, R8, ‘m’ and ‘n’ are as defined in compound formula (I). Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (ID): Formula (ID) where in, R1, R2, R3, R6, ‘m’ and ‘n’ are as defined in compound Formula (I). * Represents chiral center. Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (IE): Formula (IE) where in, R3, R6, ‘m’ and ‘n’ are as defined in compound Formula (I). * Represents chiral center. According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC), (ID) and (IE) wherein, R1 and R2 are methoxy. According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC), (ID) and (IE) wherein ring According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC), (ID) and (IE) wherein R4 and R5 taken together with the carbon atoms to which they are attached to form cycloalkyl; wherein cycloalkyl is (includes isomers and ) According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC), (ID) and (IE) wherein R7 and R8 are hydrogen. According to yet another embodiment, there is provided a compound of Formula (I),(IA), (IB), (IC), (ID) and (IE) wherein ring In further yet another embodiment, the compounds of Formula (I) structurally encompass all stereoisomers, enantiomers and diastereomers, and pharmaceutically acceptable salts that may be contemplated from the chemical structure of the general formula (I) described herein. The absolute configuration at an asymmetric atom is specified by either R or S. Resolved compounds whose absolute configuration is not known can be designated by (+) or (-) depending on the direction in which they rotate plane polarized light. When a specific stereoisomer is identified, this means that said stereoisomer is substantially free, i.e. associated with less than 50%, preferably less than 20%, more preferably less than 5%, in particularly less than 2% or 1% of the other isomers. Thus, when a compound of Formula (I) is for instance specified as (R), this means that the compound is substantially free of (S) isomer; when the compound of Formula (I) is for instance specified as E, this means that the compound is free of the Z isomer; when the compound of Formula (I) is for instance specified as cis isomer, this means that the compound is free of the trans isomer. The compounds of the Formula (I) are existed in stereoisomeric form at specified stereo centers as “R” or “S” isomers. The stereospecificity at particular stereocenters were controlled in the precursor synthesis (Intermediates) by using chiral resolution agents like (S)- 1-phenylethan-1-amine and (R)-1-phenylethan-1-amine and the like. The isomers can also be separated by using chiral HPLC separation techniques in the final step of synthesis. The stereospecificity at the particular stereocenter can be confirmed by using the technique single crystal XRD. The single crystals of the corresponding molecules were developed by using appropriate solvents like methanol, ethyl acetate, dichloromethane, ethanol, acetonitrile, acetone, THF, isopropanol, diethyl ether or in the combination of solvents. The stereochemistry at the particular stereocenter, structurally can be represented as follows. The present invention also provides a pharmaceutical composition that includes at least one compound of Formula (I) as described herein and at least one pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Specifically, the pharmaceutical composition comprises a therapeutically effective amount of at least one compound described herein. The compound(s) present in the composition may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or may be diluted by a carrier, or enclosed within a carrier which may be in the form of a capsule, sachet, or other container. The compounds and pharmaceutical compositions described herein are useful in modulating kinase enzymatic activity and accordingly modulating kinase-dependent associated diseases and conditions such as cancers. Below are the representative compounds, which are illustrative in nature only and are not intended to limit to the scope of the invention (Nomenclature has been generated from ChemBioDraw Ultra 23.1.2 version): N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)fumaramide, N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)maleamide, N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)succinimide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclobutane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclobutane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopentane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopentane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclohexane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclohexane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl- 3,3-dimethylcyclopropane-1,2-dicarboxamid, (1R,2S)-N1-(3-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl- 3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-methylphenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-methylphenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2- methylphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2- methylphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl- 3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl- 3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-chlorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-chlorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(5-methylisoxazol-3-yl)cyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(5-methylisoxazol-3-yl)cyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(3-morpholinopropoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)phenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, 4-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7-yl)oxy)piperidine-1- carboxylate, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(piperidin-4-yloxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetate, (1S,2R)-N1-(4-((7-((1-acryloylpiperidin-4-yl)oxy)-6-methoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, 4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxamido)phenoxy)-6,7-dimethoxyquinoline 1-oxide, (1R,2S)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-hydroxy-7-methoxyquinolin-4-yl)oxy)phenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(2,2,2-trifluoroethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, tert-butyl 4-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6-yl)oxy)piperidine-1- carboxylate, (1S,2R)-N1-(4-((6,7-dihydroxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(piperidin-4-yloxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetate, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-((1-(2,2,2-trifluoroacetyl)piperidin-4- yl)oxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(2-methoxyethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(2,2,2-trifluoroethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, tert-butyl (2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)ethyl)carbamate, (1S,2R)-N1-(4-((6,7-bis(2-methoxyethoxy)quinolin-4-yl)oxy)-3-fluorophenyl)-N2- (4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(2-methoxyethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6-(2-aminoethoxy)-7-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid, (1S,2R)-N1-(4-((7-(3-aminopropoxy)-6-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid, tert-butyl (3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)carbamate, tert-butyl (3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)carbamate, (1S,2R)-N1-(4-((6-(3-aminopropoxy)-7-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid, (1S,2R)-N1-(4-((6,7-bis(3-methoxypropoxy)quinolin-4-yl)oxy)-3-fluorophenyl)-N2- (4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(3-methoxypropoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(3-methoxypropoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, tert-butyl (2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)ethyl)carbamate, (1S,2R)-N1-(4-((7-(2-aminoethoxy)-6-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid, tert-butyl 4-(3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)piperazine-1-carboxylate, tert-butyl 4-(2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)ethyl)piperazine-1-carboxylate, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(2-(piperazin-1-yl)ethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(3-(piperazin-1-yl)propoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid, tert-butyl 4-(2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)ethyl)piperazine-1-carboxylate, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(2-(piperazin-1-yl)ethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid, tert-butyl 4-(3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)piperazine-1-carboxylate, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(3-(piperazin-1-yl)propoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid, 4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxamido)phenoxy)-6-hydroxy-7-methoxyquinoline 1-oxide, (1S,2R)-N1-(3-fluoro-4-((6-(3-hydroxypropoxy)-7-methoxyquinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(6-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-3-yl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(((S)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide (1S,2R)-N1-(6-((6,7-dimethoxyquinolin-4-yl)oxy)-5-fluoropyridin-3-yl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, tert-butyl 4-(((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)methyl)piperidine-1-carboxylate, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(piperidin-4-ylmethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)thio)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-N2,3,3-trimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-N2,3,3-trimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(2-methylbenzo[d]thiazol-6-yl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(2-methylbenzo[d]thiazol-6-yl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(2,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(2,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorobenzyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorobenzyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- methoxyphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- methoxyphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-9-yl)oxy)-3-fluorophenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(5-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-2-yl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(5-methylthiazol-2-yl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(5-methylthiazol-2-yl)cyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-(((3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl)oxy)-7- methoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide, tert-butyl 4-(((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)methyl)piperidine-1-carboxylate, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(((S)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(benzo[d]thiazol-2-yl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(benzo[d]thiazol-2-yl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-phenylcyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-phenylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-(((3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl)oxy)-6- methoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-((tetrahydro-2H-pyran-4- yl)methoxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-((tetrahydro-2H-pyran-4- yl)methoxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(piperidin-4-ylmethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid, (1S,2R)-N1-(4-((6-(2-(tert-butoxy)ethoxy)-7-methoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(2-((6,7-dimethoxyquinolin-4-yl)oxy)pyrimidin-5-yl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((7-(2-(tert-butoxy)ethoxy)-6-methoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-((3-methyloxetan-3-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-((3-methyloxetan-3-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(((R)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(((R)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(((S)-oxetan-2-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(((S)-oxetan-2-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(quinoxalin-6-yl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(quinoxalin-6-yl)cyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(quinolin-3-yl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(quinolin-3-yl)cyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(pyridin-3-yl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(pyridin-3-yl)cyclopropane-1,2-dicarboxamide, (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(naphthalen-1-yl)cyclopropane-1,2-dicarboxamide, (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl- N2-(naphthalen-1-yl)cyclopropane-1,2-dicarboxamide and (1S,2R)-N1-(4-((6,7-bis(methoxy-d3)quinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof. DETAILED DESCRIPTION OF THE INVENTION The present invention provides quinoline compounds, which are modulating kinase enzymatic activity and processes for the synthesis of these compounds and their pharmaceutically acceptable salts thereof, together with pharmaceutically acceptable carriers, excipients or diluents, which can be used for the treatment of cancer. The following definitions apply to the terms as used herein: The term “alkyl” refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing no unsaturation, having from one to eight carbon atoms, and which is attached to the rest of the molecule by a single bond, e.g., methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n-butyl, 2-methylpropyl (isobutyl), n-pentyl, and 1,1-dimethylethyl (t-butyl). Alkyl group can be substituted or unsubstituted with one or more suitable groups. The term “alkenyl” refers to a hydrocarbon chain that may be a straight chain or branched chain, containing the indicated number of carbon atoms having at least one -C=C-, for example, a C2-C6 alkenyl group may have from 2 to 6 (inclusive) -C=C- atoms in it. Examples of C2-C6 alkenyl groups include, but are not limited to ethylene, prop-l-ene, but-l- ene, but-2-ene, pent-l-ene, pent-2-ene, hex-l-ene, hex-2-ene and the like. The term “alkoxy” refers to a straight or branched hydrocarbon chain with oxygen radical consisting carbon and hydrogen atoms, containing saturation or unsaturation, having from one to eight carbon atoms, and which is attached through oxygen atom to the rest of the molecule by a single bond, e.g., methyloxy, ethyloxy, n-propyloxy, 1-methylethyloxy (isopropyloxy), n-butyloxy, n-pentyloxy, and 1,1-dimethylethyloxy (t-butyloxy). The term “aryl” refers to an aromatic radical having from 6 to 14 carbon atoms such as but are not limited to, phenyl, naphthyl, tetrahydronapthyl, indanyl, and biphenyl. The aryl group can be substituted or unsubstituted. If it is substituted the substituents are selected from alkyl, alkenyl, cycloalkyl, halo, hydroxyl, alkoxy, cyano, nitro, amino, acetyl, -N(H)-acetyl, S(O)2-alkyl, thiol, thioalkyl, aminoalkyl or heterocyclyl. The term "arylalkyl" refers to an alkyl group, as defined above, wherein one or more of the alkyl group's hydrogen atoms has been replaced with aryl group as defined above. Representative examples of arylalkyl group include, but are not limited to phenylmethyl, phenylethyl, phenylpropyl, phenylbutyl and the like. Arylalkyl group can be substituted or unsubstituted with one or more suitable groups. The term “cyano” group refers to a -CN group. The term “cycloalkyl” denotes a non-aromatic mono or multicyclic ring system of from 3 to about 12 carbon atoms, such as but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples of multicyclic cycloalkyl groups include, but are not limited to, perhydronapththyl, adamantyl and norbornyl groups, bridged cyclic groups and spirobicyclic groups, e.g., spiro (4,4) non-2-yl. Cycloalkyl group can be substituted or unsubstituted with one or more suitable groups. The term "Cycloalkylalkyl" refers to an alkyl group, as defined above, wherein one or more of the alkyl group's hydrogen atoms has been replaced with cycloalkyl group as defined above. Representative examples of a cycloalkylalkyl group include, but are not limited to cyclopropylmethyl, cyclobutylmethyl, cyclohexylmethyl, cyclopentylmethyl, cyclohexylmethyl and the like. A cycloalkylalkyl group can be unsubstituted or substituted with one or more suitable groups. As used herein, "cycloalkyloxy" refers to an -O-cycloalkyl group wherein the cycloalkyl group is as defined above. The term “amino” represents -NH2. The term “nitro” represents -NO2. The terms "halogen" or "halo" includes fluorine, chlorine, bromine, or iodine. The term “hydroxy” group refers to an -OH group. The term “haloalkyl” refers to an alkyl group in which at least one hydrogen is replaced with a halogen. Thus, the term “haloalkyl” includes monohaloalkyl (alkyl substituted with one halogen atom) and polyhaloalkyl (alkyl substituted with two or more halogen atoms). Example haloalkyl groups include CF3, CH2-CF3, C2F5, CHF2, CH2F, CCl3, CHCl2, C2Cl5 and the like. The term “heteroaryl” refers to an aromatic heterocyclic ring radical. The heteroaryl ring radical may be attached to the main structure at any heteroatom or carbon atom that results in the creation of a stable structure. Examples, of heteroaryl groups are acridinyl, furyl, thienyl, benzothienyl, cinnolinyl, isoxazolyl, benzothiazolyl, thiadiazolyl, thiazolyl, imidazolyl, imidazopyridinyl, oxazolyl, oxadiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, isoxazolyl, isothiazolyl, pyrrolyl, pyranyl, tetrahydropyranyl, pyrrolopyridazine, pyrazolyl, pyridyl, pyrimidinyl, quinolinyl, quinoxalinyl, quinazolinyl, isoquinolinyl, purinyl, carbazolyl, phthalazinyl, benzothiophenyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, 1,5-naphthyridinyl, 1,7-naphthyridinyl, 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinyl, 5,6,7,8- tetrahydroquinolinyl, 1,2,3,4-tetrahydroquinolinyl, 1,2,3,4-tetrahydroisoquinolinyl, indolinyl, indazolyl, indolyl, isoindolyl, thiophenyl, pyrazinyl, pyridazinyl, diazinyl, triazinyl, and tetrazinyl. The heteroaryl group can be substituted or unsubstituted. If it is substituted the substituents are selected from alkyl, alkenyl, cycloalkyl, halo, hydroxyl, alkoxy, cyano, nitro, amino, acetyl, -N(H)-acetyl, S(O)2-alkyl, thiol, thioalkyl, aminoalkyl or heterocyclyl. The term "heterocyclyl" refers to a non-aromatic, saturated or partially saturated monocyclic or polycyclic ring system of 3 to 15 members having at least one heteroatom or heterogroup selected from O, N, S, S(O), S(O)2, or NH with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen and sulfur. A monocyclic heterocyclyl may typically contain 4 to 7 ring atoms. Examples of “Heterocyclyl” include, but are not limited to azetidinyl, oxetanyl, imidazolidinyl, pyrrolidinyl, oxazolidinyl, thiazolidinyl, pyrazolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, pyrrolidin-2-one, tetrahydropyranyl, morpholinyl, oxapiperazinyl, oxapiperidinyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiophenyl, dihydropyranyl, indolinyl, azepanyl, 1,2,3,4- tetrahydroisoquinolinyl, 2,3-dihydro-1,4-dioxinyl, 1,4,7,10-tetraoxacyclododecanyl, (3as,6as)-hexahydrofuro[2,3-b]furanyl, 3,4-dihydro-2H-benzo[b][l,4]oxazinyl, and N-oxides thereof. Attachment of a heterocyclyl substituent can occur via either a carbon atom or a heteroatom. A heterocyclyl group can be unsubstituted or substituted with one or more suitable groups by one or more aforesaid groups. The term “heterocyclylalkyl” is same as “heterocyclyl” refers to a non-aromatic, saturated or partially saturated monocyclic or polycyclic ring system of 3 to 15 members having at least one heteroatom or heterogroup selected from O, N, S, S(O), S(O)2, or NH with the remaining ring atoms being independently selected from the group consisting of carbon, oxygen, nitrogen, sulfur and the heterocyclyl group was linked to alkyl chain. The examples of alkyl chain include but not limited to methyl, ethyl, n-propyl, 1-methylethyl (isopropyl), n- butyl, n-pentyl, and 1,1-dimethylethyl (t-butyl). The Examples of “Heterocyclylalkyl” include, but are not limited to propylpyperazine, ethylpyperazine, methylpiperidine, methylazetidine, and N-oxides thereof. Attachment of a heterocyclyl substituent can occur via either a carbon atom or a heteroatom. The term “substituted” refers to replacement of one or more hydrogen radicals in a given structure with a radical of a specified substituent including, but are not limited to: hydroxy, halo, carboxyl, cyano (CN), nitro, oxo (=O), thio (=S), alkyl, methyl sulfonyl, haloalkyl, alkoxy, alkenyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, amino, -C(O)O-alkyl, heterocyclyl, heteroaryl, heterocyclylalkyl, heteroarylalkyl, alkylthio, arylthio, aryloxy, amino carbonyl, alkoxycarbonyl, alkylamino, arylamino, acyl, carboxylic acid, sulfonic acid, sulfonyl, phosphonic acid, and aliphatic. It is understood that the substituent may be further substituted. The term "prodrug" denotes a derivative of a compound, which derivative, when administered to warm blooded animals, e.g. humans, is converted into the compound (drug). The enzymatic and / or chemical hydrolytic cleavage of the compounds of the present invention occurs in such a manner that the proven drug form (parent carboxylic acid drug) is released, and the moiety or moieties split off remain nontoxic or are metabolized so that nontoxic metabolic products are produced. For example, a carboxylic acid group can be esterified, e.g., with a methyl group or ethyl group to yield an ester. When an ester is administered to a subject, the ester is cleaved, enzymatically or non-enzymatically, reductively, oxidatively, or hydrolytically, to reveal the anionic group. An anionic group can be esterified with moieties (e.g., acyloxymethyl esters) which are cleaved to reveal an intermediate compound which subsequently decomposes to yield the active compound. A discussion of the use of prodrugs is provided by T. Higuchi and W. Stella, "Pro-drugs as Novel Delivery Systems," Vol.14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987. The term "treating" or "treatment" of a state, disease, disorder or condition includes: (1) preventing or delaying the appearance of clinical symptoms of the state, disease, disorder or condition developing in a subject that may be afflicted with or predisposed to the state, disease, disorder or condition but does not yet experience or display clinical or subclinical symptoms of the state, disease, disorder or condition; (2) inhibiting the state, disease, disorder or condition, i.e., arresting or reducing the development of the state, disease, disorder or condition or at least one clinical or subclinical symptom thereof; or (3) relieving the state, disease, disorder or condition, i.e., causing regression of the state, disease, disorder or condition or at least one of its clinical or subclinical symptoms. The benefit to a subject receiving treatment is either statistically significant or at least perceptible to the subject or to the physician. The term "subject" includes mammals (especially humans) and other animals, such as domestic animals (e.g., household pets including cats and dogs) and non-domestic animals (such as wildlife). A "therapeutically effective amount" means the amount of a compound that, when administered to a subject for treating a state, disease, disorder or condition, is sufficient to effect such treatment. The "therapeutically effective amount" will vary depending on the compound, the state, disease, disorder or condition and its severity and the age, weight, physical condition and responsiveness of the subject receiving treatment. The compounds of the present invention may form salts. Non-limiting examples of pharmaceutically acceptable salts forming part of this invention include salts derived from inorganic bases salts of organic bases salts of chiral bases, salts of natural amino acids and salts of non-natural amino acids. Certain compounds of the present invention are capable of existing in stereoisomeric forms (e.g., diastereomers, enantiomers, racemates, and combinations thereof). With respect to the overall compounds described by the formula (I), the present invention extends to these stereoisomeric forms and to mixtures thereof. To the extent prior art teaches synthesis or separation of particular stereoisomers, the different stereo isomeric forms of the present invention may be separated from one another by the methods known in the art, or a given isomer may be obtained by stereospecific or asymmetric synthesis. Tautomeric forms and mixtures of compounds described herein are also contemplated. In a further aspect, the compounds of the present invention can also contain unnatural proportions of atomic isotopes at one or more of the atoms that constitute such compounds. For example, the present invention also embraces isotopically-labelled variants of the present invention which are identical to those recited herein, but for the fact that one or more atoms of the compound are replaced by an atom having the atomic mass or mass number different from the predominant atomic mass or mass number usually found in nature for the atom. All isotopes of any particular atom or element as specified are contemplated within the scope of the compounds of the invention, and their uses. Exemplary isotopes that can be incorporated in to compounds of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, sulfur, fluorine, chlorine and iodine, such as2H ("D"),3H,nC,13C,14C,13N,15N,15O,17O,18O,32P,33P,35S,18F,36C1,123I and125I. Particular isotopes are -CD3 or -C(D2)-. Isotopically-labelled compounds of the present inventions can generally be prepared by following procedures analogous to those disclosed in the Schemes and / or in the Examples herein below, by substituting an isotopically-labelled reagent for a non-isotopically-labelled reagent. PHARMACEUTICAL COMPOSITIONS The pharmaceutical compositions provided in the present invention include at least one compound described herein and at least one pharmaceutically acceptable excipient (such as a pharmaceutically acceptable carrier or diluent). Specifically, the contemplated pharmaceutical compositions include a compound(s) described herein in an amount sufficient to treat viral infection in a subject. The subjects contemplated include, for example, a living cell and a mammal, including human. The compound of the present invention may be associated with a pharmaceutically acceptable excipient (such as a carrier or a diluent) or be diluted by a carrier, or enclosed within a carrier which can be in the form of a capsule, sachet, or other container. Examples of suitable carriers include, but are not limited to, water, salt solutions, alcohols, polyethylene glycols, peanut oil, olive oil, gelatin, lactose, terra alba, sucrose, dextrin, magnesium carbonate, sugar, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid, lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, fatty acid esters, and polyoxyethylene. The carrier or diluent may include a sustained release material, such as, for example, glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The pharmaceutical composition may also include one or more pharmaceutically acceptable auxiliary agents, wetting agents, emulsifying agents, suspending agents, preserving agents, salts for influencing osmotic pressure, buffers, sweetening agents, flavoring agents, colorants, or any combination of the foregoing. The pharmaceutical composition of the invention may be formulated so as to provide quick-, sustained-, or delayed-release of the active ingredient after administration to the subject by employing procedures known in the art. The pharmaceutical compositions described herein may be prepared, e.g., as described in Remington: The Science and Practice of Pharmacy, 20thEd., 2003 (Lippincott Williams & Wilkins). For example, the active compound can be mixed with a carrier, or diluted by a carrier, or enclosed within a carrier, which may be in the form of an ampule, capsule, or sachet. When the carrier serves as a diluent, it may be a solid, semi-solid, or liquid material that acts as a vehicle, excipient, or medium for the active compound. The pharmaceutical compositions may be in conventional forms, for example, capsules, tablets, solutions, suspensions, injectables or products for topical application. Further, the pharmaceutical composition of the present invention may be formulated so as to provide desired release profile. The route of administration may be any route which effectively transports the active compound to the appropriate or desired site of action. Suitable routes of administration include, but are not limited to, oral, nasal, pulmonary, buccal, subdermal, intradermal, transdermal, parenteral, rectal, depot, subcutaneous, intravenous, intraurethral, intramuscular, intranasal, ophthalmic (such as with an ophthalmic solution) or topical (such as with a topical ointment). The oral route is specifically suitable. Solid oral formulations include, but are not limited to, tablets, capsules (soft or hard gelatin), dragees (containing the active ingredient in powder or pellet form), troches and lozenges. Tablets, dragees, or capsules having talc and / or a carbohydrate carrier or binder or the like are particularly suitable for oral application. Exemplary carriers for tablets, dragees, or capsules include lactose, cornstarch, and / or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed. A typical tablet that may be prepared by conventional tableting techniques. Liquid formulations include, but are not limited to, syrups, emulsions, soft gelatin and sterile injectable liquids, such as aqueous or non-aqueous liquid suspensions or solutions. For parenteral application, particularly suitable are injectable solutions or suspensions, specifically aqueous solutions with the active compound dissolved in polyhydroxylated castor oil. METHODS OF TREATMENT The compounds of the present invention can inhibit, regulate, and / or modulate tyrosine kinases such as KDR (VEGFR2), MET (C-MET), RET, AXL, TEK (Tie 2), EGFRs. The present disclosure relates to quinoline compounds for use in modulating kinase enzymatic activity and accordingly modulating kinase-dependent associated diseases and conditions such as cancers like Lung, Thyroid carcinoma, Ovarian carcinoma, Pancreatic carcinoma, Prostatic carcinoma, Renal cell carcinoma, Liver, Skin cancer, Hepatocellular carcinoma, Breast carcinoma, Colorectal carcinoma, Oral squamous cell carcinoma, Lung adenocarcinoma or Endometrial cancer. Gastro intestinal cancers (GIST), colon cancer or Brain cancer. In certain embodiments, the present invention provides uses of a compound of the present invention for the preparation of a medicament, e.g., for the treatment of cancer. In certain embodiments, the present invention provides methods for treating cancer, wherein the method comprises administration of a therapeutically effective amount of a compound of the present invention to the subject in need thereof. In certain embodiments, the present invention provides methods for inhibiting growth of tumor cells and / or metastasis by administering a therapeutically effective amount of a compound of the present invention to the subject in need thereof. Representative tumor cells include cells of a cancer such as but not limited to breast cancer, prostate cancer, melanoma, renal cancer, colon cancer and lung cancer, skin cancer, bone cancer, pancreatic cancer, head and neck cancer, intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the vagina, carcinoma of the cervix, Hodgkin's lymphoma, non-Hodgkin's lymphoma, esophageal cancer, small intestine cancer, endocrine cancer, thyroid cancer, parathyroid cancer, soft tissue sarcoma, urethra cancer, chronic or acute leukemias including acute myeloid leukemia, chronic myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, solid tumors of childhood, lymphocytic lymphoma, bladder cancer, kidney cancer, renal pelvis carcinoma, neoplasm of the central nervous system (CNS), non- small cell lung cancer (NSCLC), SCLC, primary CNS lymphoma, tumor angiogenesis, spinal axis tumor, brain stem glioma, pituitary adenoma, Kaposi's sarcoma, epidermoid cancer, squamous cell cancer. The compounds of the present invention may be used as single drugs (monotherapy) or combination with one or more other agents (Combination therapy). The compounds may be used by themselves, or preferably, in a pharmaceutical composition in which the compound is mixed with one or more pharmaceutically acceptable materials. The compounds of the present invention may be administered in combination with one or more other drugs (1) to complement and / or enhance effect of the compound of the present invention, (2) to modulate pharmacodynamics, improve absorption, or reduce dosage of the compound of the present invention, and / or (3) to reduce or ameliorate the side effects of the compound of the present invention. As used herein, the phrase "Combination administration" refers to any form of administration of two or more different therapeutic compounds such that the second compound is administered while the previously administered therapeutic compound is still effective in the body (e.g., the two compounds are simultaneously effective in the patient, which may include synergistic effects of the two compounds). For example, the different therapeutic compounds can be administered either in the same formulation or in a separate formulation, either concomitantly or sequentially. In certain embodiments, the different therapeutic compounds can be administered within one hour, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours or a week of one another. Thus, an individual who receives such treatment can benefit from a combined effect of different therapeutic compounds. The respective compounds may be administered by the same or different route and the same or different method. The compounds of the present invention directed to the treatment of cancer, the compound of the present invention can be used with an existing chemo therapeutic conjointly using a single pharmaceutical composition or a combination of different pharmaceutical compositions concomitantly or in a mixture form. Examples of the chemotherapeutic include an alkylation agent, nitrosourea agent, antimetabolite, anticancer antibiotics, vegetable-origin alkaloid, topoisomerase inhibitor, hormone drug, hormone antagonist, aromatase inhibitor, P- glycoprotein inhibitor, platinum complex derivative, other immunotherapeutic drugs and other anticancer drugs. Further, it a compound of the invention can be used administered conjointly with a cancer treatment adjunct, such as a leucopenia (neutropenia) treatment drug, thrombocytopenia treatment drug, antiemetic and cancer pain intervention drug, concomitantly or in a mixture form. Chemotherapeutic agents that may be conjointly administered with compounds of the invention, with one or more of the drugs , but not limited to : amsacrine, aminoglutethimide, asparaginase, anastrozole, Apalutamide, Enzalutamide, bicalutamide, bortezomib, buserelin, busulfan, campothecin, capecitabine, carboplatin, carfilzomib, carmustine, chlorambucil, chloroquine, cisplatin, cladribine, clodronate, colchicine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, demethoxyviridin, dexamethasone, dichloroacetate, dienestrol, diethylstilbestrol, docetaxel, doxorubicin, epirubicin, estradiol, estramustine, etoposide, everolimus, exemestane, filgrastim, fludarabine, fludrocortisone, fluorouracil, fluoxymesterone, flutamide, gemcitabine, genistein, goserelin, hydroxyurea, idarubicin, ifosfamide, imatinib, interferon, irinotecan, ironotecan, lenalidomide, letrozole, leucovorin, leuprolide, levamisole, lomustine, lonidamine, mechlorethamine, medroxyprogesterone, megestrol, melphalan, mercaptopurine, mesna, metformin, methotrexate, mitomycin, mitotane, mitoxantrone, nilutamide, nocodazole, octreotide, oxaliplatin, paclitaxel, pamidronate, pentostatin, perifosine, plicamycin, pomalidomide, porfimer, procarbazine, raltitrexed, rituximab, sorafenib, streptozocin, sunitinib, suramin, tamoxifen, temozolomide, temsirolimus, teniposide, testosterone, thalidomide, thioguanine, thiotepa, titanocene dichloride, topotecan, trastuzumab, tretinoin, vinblastine, vincristine, vindesine, and vinorelbine. In certain embodiments, the compound of the present invention of Formula (I), (IA), (IB), (IC), (ID) and (IE) conjointly administered with non-chemical methods of cancer treatment. In certain embodiments, a compound of the invention may be conjointly administered with radiation therapy. In certain embodiments, a compound of the invention may be conjointly administered with surgery, with radiofrequency, microwave, laser, high- intensity focused ultrasound, cryoablation, and irreversible electroporation or with any combination of these. In certain embodiments, the compound of the present invention of Formula (I), (IA), (IB), (IC), (ID) and (IE) may be administered in combination with one or more other kinase inhibitors like MEK, EGFR, CDK, Bruton kinase, KRAS, ALK, PI3K, BRAF, BCR-ABL, ROS1, FGFR, JAK, PARP, or any which show better efficacy / outcome, complimentarily, in combinations in certain cancers, where two or more MOA. The drugs for combination therapy include, for example, antibiotics, antifungal agents, sedatives, anesthetics, antiulcer drugs, antidepressants, antiarrhythmic agents, antiprotozoal agents, tranquilizers, hypotensive diuretic drugs, anticoagulants, antipsychotics, muscle relaxants, antiepileptic drugs, hypotensive diuretics, antitussives and expectorant drugs, antiallergic drugs, antinarcotics, cardiac stimulants, therapeutic drugs for arrhythmia, vasodilators, vasoconstrictors, therapeutic drugs for diabetes, vitamins, antiasthmatics, therapeutic agents for atopic dermatitis, antipruritic drugs, therapeutic agents for allergic rhinitis, hyper tensors, endotoxin-antagonists or -antibodies, signal transduction inhibitors, inhibitors of anti-inflammatory mediator activity, inhibitors of inflammatory mediator activity, antibodies to inhibit inflammatory mediator activity, antibodies to inhibit anti- inflammatory mediator activity and the like. In any one of the foregoing embodiments, the cancer or proliferative disorder is selected from a solid tumor, malignant tumor, brain cancer, kidney cancer, liver, stomach, vagina, ovaries, gastric tumors, endometrial cancer breast, bladder colon, prostate, pancreas, lung, cervix, testis, skin, bone or thyroid; sarcoma, glioblastomas, neuroblastomas, multiple myeloma, gastrointestinal cancer, a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, adenoma, adenocarcinoma, keratoacanthoma, epidermoid carcinoma, large cell carcinoma, non-small-cell lung carcinoma, Hodgkins and Non-Hodgkins lymphomas, a mammary carcinoma, follicular carcinoma, papillary carcinoma, seminoma. In certain embodiments the compounds of the present invention can be chemically linked to monoclonal antibody or Bispecific Antibodies generally called as Antibody Drug Conjugates (ADCs). Antibody–drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. ADCs combine the targeting properties of monoclonal antibodies with the cancer-killing capabilities of cytotoxic drugs. Unlike conventional chemotherapy treatments, which can damage healthy cells, antibody drug conjugates (ADCs) are targeted medicines that deliver chemotherapy agents to cancer cells. ADCs deliver the chemotherapy via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. After binding to the target (cancer protein or receptor), the ADC releases a cytotoxic drug into the cancer cell. Such examples of cleavable or non-cleavable linkers are (6-maleimidocaproyl) hydrazone, 4-(4-acetylphenoxy) butanoic acid, a disulfide-containing ADC, Peptide-based linkers, also known as lysosomal protease-sensitive linkers, such as valine–citrulline (Val–Cit), phenylalanine–lysine (Phe– Lys), and valine–alanine (Val–Ala) dipeptide linkers, are the most widely used linkers in ADC design, Glycosidase-Sensitive Linkers like β-Glucuronidase-cleavable linkers, Phosphatase- Cleavable Linkers and Non-cleavable linkers like thioether or maleimidocaproyl (MC). In certain embodiments the compounds of the present invention can be linked to protein degraders through a linker generally called as proteolysis-targeting chimera (PROTAC) protein degraders. A major class of molecules that enable such proteins to be modulated through TPD (Target Protein Degraders) are known as proteolysis-targeting chimera (PROTAC) protein degraders. These are hetero bifunctional small molecules consisting of two ligands joined by a linker: one ligand recruits and binds a protein of interest (POI) while the other recruits and binds an E3 ubiquitin ligase. Simultaneous binding of the POI and ligase by the PROTAC induces ubiquitylation of the POI and its subsequent degradation by the ubiquitin–proteasome system (UPS), after which the PROTAC is recycled to target another copy of the POI. It is this catalytic-type mechanism of action (MoA) and event-driven pharmacology that distinguishes PROTACs from classical inhibitors, which have a one-to-one relationship with the POI and whose pharmacology is driven by stoichiometry and, usually, by interactions with a catalytic site; (Nature Reviews Drug Discovery volume 21, pages181–200; 2022). METHODS OF PREPARATION Compounds of the present invention can be prepared by using synthetic methods which are well established in chemical synthesis of organic compounds. Key intermediates required for synthesizing analogues are either commercially available, or can be prepared by the methods published in the literature. For example, the key intermediates in the present invention were prepared by modifying the procedures published in Front Chem. 2022; 10: 1074331, HETEROCYCLES, Vol.93, No.1, 2016. Further, in the following schemes, where specific bases, acids, reagents, solvents, coupling agents, etc., are mentioned, it is understood that other bases, acids, reagents, solvents, coupling agents etc., known in the art may also be used and are therefore included within the present invention. Variations in reaction conditions, for example, temperature and / or duration of the reaction, which may be used as known in the art, are also within the scope of the present invention. All the stereoisomers of the compounds in these schemes, unless otherwise specified, are also encompassed within the scope of this invention. Another embodiment of the present invention provides process for preparation of the compounds of general formula (I) are set forth in the below generalized schemes. One of skilled in the art will recognize that below generalised schemes can be adapted to produce the compounds of general formula (I) and pharmaceutically acceptable salts according to the present invention. Wherein all symbols / variables are as defined earlier unless otherwise stated. Scheme-1: R3, R6, ring A, ‘m’ and ‘n’ are as defined in compound of Formula (I). * Represents chiral centres. The chloroquinoline compounds of formula (i) was converted to the compounds of formula (iii) by reacting with compounds of formula (ii) with bases such as sodium tert- butoxide or potassium tert-butoxide in solvents such as N,N-Dimethylformamide or N.N- dimethylacetamide or the like at heating conditions. The compounds of formula (iii) were converted to compounds of Formula (A) by coupling with compounds of formula (iv) with reagents such as EDC.HCl or T3P and catalyst such as 4-Dimethylamino pyridine (DMAP) in solvents such as Dichloromethane (DCM) or N-Methyl-2-pyrrolidone (NMP) or the like. Both the isomers of the compounds of Formula (A) are separated by using the technique chiral HPLC. Scheme-II: R3, R4, R5, R6, R8, ring A, ‘m’ and ‘n’ are as defined in compound of Formula (I). * Represents chiral centres. The chloroquinoline compounds of formula (i) was converted to the compounds of formula (iii) by reacting with compounds of formula (ii) with bases such as DIPEA or the like in solvents such as N-Methyl-2-pyrrolidone or the like at heating conditions. The compounds of formula (iii) converted to the compounds of formula (iv) with reducing agent such as Iron powder, under acidic conditions with reagents like acetic acid or ammonium chloride in solvents such as methanol or ethanol and water or the like at heating conditions. The compounds of formula (iv) were converted to the compounds of Formula (B) by coupling with compounds of formula (v) with reagents such as EDC.HCl or T3P and catalyst such as 4-Dimethylamino pyridine (DMAP) in solvents such as Dichloromethane (DCM) or N- Methyl-2-pyrrolidone (NMP) or the like. Both the isomers of the compounds of formula (B) are separated by using the technique chiral HPLC. Scheme-III: R1, R3, R6, ring A, ‘m’ and ‘n’ are as defined in compound of Formula (I). * Represents chiral centres. The compound of formula (i) was protected by using the reagents such as acetic anhydride or acetyl chloride with bases like pyridine, 4-DMAP or DIPEA and the like in solvents such as DCM, chloroform, THF or the like to give compound of formula (ii). The compound of formula (ii) was converted to the compound of formula (iii) by using the method (a) reducing agent such as 10% Pd / C in solvents like methanol or ethanol or the like under hydrogenation conditions (or) method (b) with reducing agent such as Iron powder, under acidic conditions with reagents like acetic acid or ammonium chloride in solvents such as methanol or ethanol and water or the like at heating conditions. The compound of formula (iii) was converted to the compound of formula (v) by coupling with compounds of formula (iv) in solvents such as ethanol or isopropanol or the like at heating conditions. The compound of formula (v) was converted to the compound of formula (vi) in solvents such as diphenyl ether, chloro benzene, or the like at higher temperatures. The compound of formula (vi) was converted to the compound of formula (vii) with reagents like phosphorous oxychloride, thionyl chloride and oxalyl chloride and the like in solvents such as chloroform DMF / ACN or the like at heating conditions. The protecting group of compounds of formula (vii) was deprotected to the compound of formula (viii) by using the bases such as sodium hydroxide or potassium hydroxide in solvents such as ethanol or methanol and water or the like. The compound of formula (viii) was converted to the compound of formula (ix) by protecting with benzyl bromide with bases such as potassium carbonate or the like in solvents such as N,N- dimethylformamide or the like. The compounds of formula (ix) were converted to the compounds of formula (xi) by coupling with compounds of formula (x) with bases like potassium carbonate or N,N-diisopropyl ethylamine in solvents such as diphenyl ether or N- methyl-2-pyrrolidone or the like at higher temperature conditions. The compounds of formula (xi) were converted to the compounds of formula (xii) by using the reducing agent such as Iron powder, under acidic conditions with reagents like acetic acid or ammonium chloride in solvents such as methanol or ethanol and water or the like at heating conditions. The compounds of formula (xii) were converted to the compounds of formula (xiv) by coupling with compounds of formula (xiii) with reagents such as EDC.HCl or T3P or the like and catalyst such as 4-Dimethylamino pyridine (DMAP) in solvents such as Dichloromethane (DCM) or N-Methyl-2-pyrrolidone (NMP) or the like. The compounds of formula (xiv) were converted to the compound of formula (xv) in two ways (1) by reacting with reagent such as 1.0 M BCl3 or the like in solvents such as dichloromethane or the like at lower temperatures (or) (2) by reacting with reagents such as methane sulfonic acid in trifluoroacetic acid or the like. The compounds of formula (xv) were converted to the compounds of formula (C) by coupling with compounds of formula (xvi) (X = -Iodo or -OMs or -OTs) with bases such as potassium carbonate or the like with or without catalyst such as TBAI in solvents such as N,N-dimethylformamide (DMF) or N-Methyl-2-pyrrolidone (NMP) or the like at room temperature or at heating conditions. Both the isomers of the compounds of formula (C) are separated by using the technique chiral HPLC. Scheme-IV: R1, R3, R6, ring A, ‘m’ and ‘n’ are as defined in compound of Formula (I). * Represents chiral centres. The compound of formula (i) was converted to the compound of formula (ii) by protecting with benzyl bromide with bases such as potassium carbonate or the like in solvents such as N,N-dimethylformamide or the like. The compound of formula (ii) was converted to the compound of formula (iii) by using the reducing agent such as Iron powder, under acidic conditions with reagents like acetic acid or ammonium chloride in solvents such as methanol or ethanol and water or the like at heating conditions. The compound of formula (iii) was converted to the compound of formula (v) by coupling with compounds of formula (iv) with reagents like trimethyl orthoformate in solvents such as ethanol or isopropanol or the like at heating conditions. The compound of formula (v) was converted to the compound of formula (vi) in solvents such as diphenyl ether or the like at higher temperatures. The compound of formula (vi) was converted to the compound of formula (vii) with reagents like phosphorous oxychloride or the like in solvents such as chloroform or combination of DMF and acetonitrile or the like under heating conditions. The compounds of formula (vii) were converted to the compounds of formula (ix) by coupling with compounds of formula (viii) with bases like potassium carbonate or N,N-diisopropyl ethylamine in solvents such as diphenyl ether or N- methyl-2-pyrrolidone or the like at higher temperature conditions. The compounds of formula (ix) were converted to the compounds of formula (x) by using the reducing agent such as Iron powder, under acidic conditions with reagents like acetic acid or the like in solvents such as methanol or ethanol and water or the like at heating conditions. The compounds of formula (x) were converted to the compounds of formula (xii) by coupling with compounds of formula (xi) with reagents such as EDC.HCl or T3P or the like and catalyst such as 4-Dimethylamino pyridine (DMAP) in solvents such as Dichloromethane (DCM) or N-Methyl-2-pyrrolidone (NMP) or the like. The compounds of formula (xii) were converted to the compound of formula (xiii) in two ways (1) by reacting with reagent such as 1.0 M BCl3 or the like in solvents such as dichloromethane or the like at lower temperatures (or) (2) by reacting with reagents such as methane sulfonic acid in trifluoroacetic acid or the like. The compounds of formula (xiii) were converted to the compounds of formula (D) by coupling with compounds of formula (xiv) (X = -Iodo or -OMs or -OTs) with bases such as potassium carbonate or the like with or without catalyst such as TBAI in solvents such as N,N-dimethylformamide (DMF) or N-Methyl-2-pyrrolidone (NMP) or the like at room temperature or at heating conditions. Both the isomers of the compounds of formula (D) are separated by using the technique chiral HPLC.

[0002] Scheme-V: R3, R6, ring A, ‘m’ and ‘n’ are as defined in compound of Formula (I). X, Y and Z are N or CH. * Represents chiral centres. The Hydroxyquinoline compound of formula (i) was converted to the compound of formula (iii) by reacting with compounds of formula (ii) with bases such as Triethylamine or potassium carbonate or cesium carbonate or the like in solvents such as N,N- dimethylformamide or acetonitrile or the like. The compounds of formula (iii) converted to the compounds of formula (iv) with reducing agent such as Iron powder, under acidic conditions with reagents like acetic acid or the like in solvents such as methanol or ethanol and water or the like at heating conditions. The compounds of formula (iv) were converted to the compounds of formula (E) by coupling with compounds of formula (v) with reagents such as EDC.HCl or T3P and catalyst such as 4-Dimethylamino pyridine (DMAP) in solvents such as Dichloromethane (DCM) or N-Methyl-2-pyrrolidone (NMP) or the like. Both the isomers of compounds of formula (E) are separated by using chiral HPLC. Scheme-VI: R1, R3, R6, ring A, m and n are as defined in compound of Formula (I). * Represents chiral centres. The compounds of formula (i) were converted to the compound of formula (ii) by reacting with reagent such as 1.0 M BBr3 in DCM or the like in solvents such as dichloromethane or the like at lower temperatures. The compounds of formula (ii) were converted to the compounds of Formula (F) by coupling with compounds of formula (iii) (X = -Iodo or -OMs or -OTs) with bases such as potassium carbonate or the like with or without catalyst such as TBAI in solvents such as N,N-dimethylformamide or N-Methyl-2- pyrrolidone (NMP) the like at room temperature or at heating conditions. Both the isomers of the compounds of Formula (F) are separated by using the technique chiral HPLC. ABBREVIATIONS: The abbreviations used in the entire specification may be summarized herein below with their particular meaning:1H NMR (Proton Nuclear Magnetic Resonance); Hz (hertz); MHz (megahertz); δ (delta); ppm (parts per million); CDCl3 (deuterated chloroform or chloroform-d), CD3OD (methanol-d4); DMSO-d6 (Dimethylsulfoxide-d6); s (singlet); d (doublet); t (triplet); m (multiplet); dd (doublet of doublet(s)); dt (doublet of triplet(s)); J (coupling constant); JAB (coupling constant); ABq (AB quartet); brs (broad singlet); ml (millilitre);oC (degree Celsius); mol (mole(s)); mmol (millimole(s)); M (Molar solution); N (Normal solution); g (gram(s)); pH (Potential of Hydrogen); eq (equivalent(s)); psi (pound per square inch); ES-MS (Electrospray ionization mass spectrometry); m / z (mass-to-charge ratio of an ion); M-H- (parent mass spectrum peak minus hydrogen-); M+Na+ (parent mass spectrum peak plus sodium+); M+H+ (parent mass spectrum peak with an added proton); DCM (Dichloromethane); DMF (N,N-dimethylformamide); DMA (N,N-dimethylacetamide); THF (Tetrahydrofuran); Na2SO4 (sodium sulphate); HCl (Hydrochloric acid); TLC (Thin Layer Chromatography); % (percentage); RB flask (Round bottom flask); TBAF (Tetra-n- butylammonium fluoride); NaOH (sodium hydroxide); KOH (potassium hydroxide); EDC.HCl (1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide Hydrochloride); MTBE (Methyl tert-butyl ether); HATU (1-H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate); h (or) hrs (hour(s)); H (Hydrogen); APCI-MS (Atmospheric-pressure Chemical ionization mass spectroscopy); DMAP (4-Dimethylaminopyridine); TBDMSCl (tert-butyldimethylsilyl chloride); T3P (Propanephosphonic acid anhydride or 1-propanephosphonic anhydride); DIPEA (N,N-Diisopropylethylamine or N-ethyl-N-isopropylpropan-2-amine); Et3N (Triethylamine); HPLC (High-Performance Liquid Chromatography); Pd / C (Palladium on Carbon); ACN (Acetonitrile); BCl3 (boron trichloride); TBAI (Tetrabutylammonium iodide); BCl3 (boron tribromide); XRD (X-ray Diffraction); EtOAc (Ethyl acetate); POCl3 (phosphorous oxychloride): Ltr (Liter / Litre), NaHCO3 (sodium bicarbonate); SOCl2 (Thionyl chloride) EXPERIMENTAL PROCEDURES The present invention is further illustrated by the following examples, which are not to be construed in any way as imposing limitations upon the scope of this disclosure, but rather are intended to be illustrative only. On the contrary, it is to be clearly understood that resort may be had to various other embodiments, modifications, and equivalents thereof which, after reading the description herein, may suggest one of ordinary skill in the art without departing from the spirit of the present invention. Thus, the skilled artisan will appreciate how the experiments and examples may be further implemented as disclosed by variously altering the following examples, substituents, reagents, or conditions. INTERMEDIATES Intermediate 1: Preparation of (1S,3R)-3-(cyclopropylcarbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: Step 1: Synthesis of Racemic 3-(cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (15 g, 107.03 mmol, 1.0 eq) in THF (150 ml) was added cyclopropylamine (6.11 g, 107.03 mmol, 1.0 eq) followed by 4-methylbenzenesulfonic acid (2.03 g, 10.7 mmol, 0.1 eq). The reaction mixture was heated at 50 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was cooled to room temperature, reaction mixture was poured into water (50 ml) and extracted with DCM (3x50 ml). The combined organic layer was washed with water (30 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was treated with ethyl acetate (10 ml) and hexane (150 ml), stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum to obtain the product (14 g) as a solid. ES-MS: m / z 196.22 (M-H)-. Step 2: Synthesis of (1S,3R)-3-(cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: A suspension of Racemic 3-(cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid (Step 1, 10 g, 50.71 mmol, 1.0 eq) and ethyl acetate (400 ml) were stirred at 40 ºC for about 15 minutes. (S)-1-phenylethan-1-amine (6.14 g or 6.46 ml, 50.71 mmol, 1.0 eq) was added and the reaction mass was stirred at room temperature for overnight. The solid was filtered and washed with ethyl acetate (2 ml). The solid was taken into RB flask, ethyl acetate (100 ml) was added and stirred at room temperature for about 6 hours. Solid was filtered and washed with ethyl acetate (5 ml). The solid was dissolved in DCM (100 ml), acidified with 1N HCl to pH 2.0 and extracted with DCM (3x100 ml). The combined organic layer was washed with water (100 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The solid was washed with hexane, filtered and dried under vacuum to obtain the product (3.0 g) as a solid. Enantiomeric purity by chiral HPLC: 96.29%;1H NMR (300 MHz, CDCl3): δ ppm 14.75 (brs, 1H), 7.32 (s, 1H), 2.82-2.75 (m, 1H), 2.02 (d, J = 8.1 Hz, 1H), 1.78 (d, J = 8.4 Hz, 1H), 1.34 (s, 3H), 1.33 (s, 3H), 0.83-0.81 (m, 2H), 0.64- 0.60 (m, 2H); ES-MS: m / z 198.02 (M+H)+. Intermediate 2: Preparation of (1R,3S)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: Step 1: Synthesis of Racemic 3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: Method 1: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (10 g, 71.357 mmol, 1.0 eq) in THF (100 ml) was added 4-fluoroaniline (6.75 ml, 71.357 mmol, 1.0 eq) followed by 4-methylbenzenesulfonic acid (1.357 g, 7.135 mmol, 0.1 eq). The reaction mixture was heated to reflux for about 5 hours. TLC indicated starting material was completed and the desired product was observed. The reaction mixture was cooled to room temperature, diluted with DCM (100 ml) and washed with water. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to obtain the title compound (14 g, yield: 78.12%) as an off-white solid.1H NMR (300 MHz, DMSO-d6): δ ppm 12.16 (s, 1H), 10.14 (s, 1H), 7.57 (dd, J = 9.0, 5.1 Hz, 2H), 7.11 (t, J = 9.0 Hz, 2H), 1.99 (d, J = 9.0 Hz, 1H), 1.88 (d, J = 9.3 Hz, 1H), 1.33 (s, 3H), 1.19 (s, 3H); ES-MS:m / z252.39(M+H)+. Method 2: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (20 g, 142.71 mmol, 1.0 eq) in THF (120 ml) was added 4-fluoroaniline (13.52 ml, 142.71 mmol, 1.0 eq) mixed in THF (20 ml) dropwise over a period of 20 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. Reaction mass was evaporated under reduced pressure until no more THF was distilled out. The resulting solid was stirred with water (200 ml) at room temperature for about 1 hour. Solid was filtered, washed with water (40 ml) and then dried under vacuum. The obtained compound was further dried under vacuum at 50-55 °C for around 2 hours to afford the title compound (30.47 g, yield: 85%) as an off-white solid. Step 2: Synthesis of (1R,3S)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: A suspension of racemic 3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane- 1-carboxylic acid (Step 1, 7.0 g, 27.859 mmol, 1.0 eq) and isopropanol (170 ml) were heated to reflux until to get a clear solution. Then, (R)-1-phenylethan-1-amine (3.5 ml, 27.859 mmol, 1.0 eq) was added and the reaction mixture was heated to reflux for about 4 hours. The reaction mixture was allowed to stir at room temperature for overnight. The reaction mixture was filtered, solid was taken into RB flask, Isopropanol (50 ml) was added, stirred for about 3 hours. Again, the mixture was filtered, solid was taken into RB flask and dried under vacuum. The solid was cooled to 0 ºC, acidified with 1N HCl to pH 3.0 and extracted with DCM (2x200 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-10% methanol in dichloromethane gradient to obtain the title compound (1.8 g, yield: 25.71%) as an off-white solid. Enantiomeric purity by chiral HPLC: 98.45%. Stereochemistry of the product was confirmed by Single crystal X-ray diffraction (XRD) analysis.1H NMR (300 MHz, CDCl3): δ ppm 8.61 (s, 1H), 7.495 (dd, J = 9.0, 4.8 Hz, 2H), 7.04 (t, J = 8.7 Hz, 2H), 2.14 (d, J = 7.8 Hz, 1H), 1.95 (d, J = 6.9 Hz, 1H), 1.40 (s, 6H); APCI-MS: m / z 252.1 (M+H)+. Intermediate 3: Preparation of (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: Step 1: Synthesis of (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: A stirred suspension of Racemic 3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 2-step 1, 21.0 g, 83.57 mmol, 1.0 eq) in isopropanol (650 ml) was heated to reflux until a clear solution was obtained. The reaction mixture was cooled to 50 ºC, (S)-1-phenylethan-1-amine (10.12 g, 83.57 mmol, 1.0 eq) was added and the reaction mixture was heated to reflux for about 3 hours. The reaction mixture was cooled to room temperature, filtered and washed with Isopropanol (20 ml). The solid was taken into RB flask, Isopropanol (150 ml) was added and stirred at room temperature for overnight. The solid was filtered, washed with isopropanol (15 ml) and then dried under vacuum. The solid was dissolved in DCM (100 ml), acidified with 1N HCl to pH 3 and extracted with DCM (3x150 ml). The combined organic layer was washed with water (150 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The solid was washed with hexane (2x50 ml), filtered and dried under vacuum to obtain the title compound (5.0 g) as a solid. Enantiomeric purity by chiral HPLC: 99.57%. Stereochemistry of the product was confirmed by Single crystal X-ray diffraction (XRD) analysis.1H NMR (300 MHz, CDCl3): δ ppm 9.27 (s, 1H), 7.53 (dd, J = 9.0, 4.8 Hz, 2H), 7.03 (t, J = 8.7 Hz, 2H), 2.12 (d, J = 7.8 Hz, 1H), 2.07 (d, J = 7.8 Hz, 1H), 1.39 (s, 6H). Intermediate 4: Preparation of (1S,3R)-3-((3,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: Step 1: Synthesis of Racemic 3-((3,4-difluorophenyl)carbamoyl)-2,2-dimethylcyclopropane- 1-carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (5.0 g, 35.678 mmol, 1.0 eq) in THF (40 ml) was added 3,4-difluoroaniline (4.6 g, 35.678 mmol, 1.0 eq). The reaction mass was stirred at 60-65 ºC for about 90 minutes. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure and dried under vacuum. Water (200 ml) was added to the reaction mass, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (500 ml) and dried under vacuum at 50-60 ºC for about 3 hours to obtain the title compound (9.3 g, yield: 96.87%) as a solid.1H NMR: (500 MHz, DMSO-d6): δ ppm 12.08 (s, 1H), 10.27 (s, 1H), 7.77-7.72 (m, 1H), 7.34 (dd, J = 19.5, 9.0 Hz, 1H), 7.24 (t, J = 5.0 Hz, 1H), 1.98 (d, J = 9.5 Hz, 1H), 1.89 (d, J = 9.5 Hz, 1H), 1.32 (s, 3H), 1.18 (s, 3H); ES-MS: m / z 270.23 (M+H)+. Step 2: Synthesis of (1S,3R)-3-((3,4-difluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: To a solution of Racemic 3-((3,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Step 1, 9.0 g, 33.426 mmol, 1.0 eq) in Isopropanol (90 ml) was added (S)-1-phenylethan-1-amine (4.05 g, 33.426 mmol, 1.0 eq). The reaction mass was stirred at reflux temperature for about 5 hours. Heating bath was removed, and the reaction mass was allowed to room temperature. The precipitate formed was filtered, washed with Isopropanol (10 ml) and then dried under vacuum for about 1 hour. Isopropanol (30 mL) was added to the above solid, stirred at room temperature for about 1 hour. Solid was filtered, washed with isopropanol (3 ml) and then dried under vacuum for about 1 hour. Further, solid was dried under vacuum at 55 ºC for about 1 hour to obtain the salt (5.3 g) as an off-white solid. DCM (45 ml) was added into the above solid compound and cool to 0-15 ºC.1N HCl (30 ml) was added at 0-15 ºC, then stirred at 25 ºC for about 2 hours to get clear solution. Organic layer was separated, DCM (500 ml) was added into the aqueous layer, stirred at room temperature for about 30 minutes. Organic layer and aqueous layers were separated. The combined organic layer was washed with water (250 ml), dried over sodium sulphate, filtered and evaporated under reduced pressure. The solid was further dried under vacuum at 50-60 ºC for about 2 hours to afford the title compound (3.5 g, yield: 38.8%) as a solid. enantiomeric purity by chiral HPLC: >99%.1H NMR: (500 MHz, DMSO-d6): δ ppm 12.08 (s, 1H), 10.28 (s, 1H), 7.77-7.72 (m, 1H), 7.34 (dd, J = 19.5, 9.0 Hz, 1H), 7.24 (t, J = 5.0 Hz, 1H), 1.98 (d, J = 9.5 Hz, 1H), 1.89 (d, J = 9.0 Hz, 1H), 1.32 (s, 3H), 1.19 (s, 3H); ES-MS: m / z 270.23 (M+H)+. Intermediate 4a: Preparation of (1R,3S)-3-((3,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: To a solution of Racemic 3-((3,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 4-step 1, 10 g, 37.14 mmol, 1.0 eq) in Isopropanol (150 ml) was added (R)-1-phenylethan-1-amine (4.5 g, 37.14 mmol, 1.0 eq). The reaction mass was stirred at reflux temperature for about 5 hours. Heating bath was removed, and the reaction mass was allowed to room temperature. The precipitate formed was filtered, washed with Isopropanol (10 ml) and then dried under vacuum for about 1 hour. Isopropanol (34 mL) was added to the above solid, stirred at room temperature for about 1 hour. Solid was filtered, washed with isopropanol (5 ml) and then dried under vacuum for about 1 hour. Further, solid was dried under vacuum at 55 ºC for about 1 hour to obtain the salt (5.8 g) as an off-white solid. DCM (100 ml) was added into the above solid compound and cool to 0-15 ºC.1N HCl (80 ml) was added at 0-15 ºC, then stirred at 25 ºC for about 2 hours to get clear solution. Organic layer was separated, DCM (500 ml) was added into the aqueous layer, stirred at room temperature for about 30 minutes. Organic layer and aqueous layers were separated. The combined organic layer was washed with water (250 ml), dried over sodium sulphate, filtered and evaporated under reduced pressure. The solid was further dried under vacuum at 50-60 ºC for about 2 hours to afford the title compound (3.3 g, yield: 33%) as a solid. Enantiomeric purity by chiral HPLC: >99%. ES-MS: m / z 270.15 (M+H)+. Intermediate 5: Preparation of (1R,3S)-3-(cyclopropylcarbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: A suspension of the Racemic 3-(cyclopropylcarbamoyl)-2,2-dimethylcyclopropane- 1-carboxylic acid (Intermediate 1-step 1, 14 g, 70.983 mmol, 1.0 eq) in ethyl acetate (420 ml) was heated at 50 ºC until the compound dissolved completely. (R)-1-phenylethan-1-amine (9.03 ml, 70.983 mmol, 1.0 eq) was added and the reaction mass was allowed to stir at room temperature for overnight. The precipitate formed was collected by filtration, washed with ethyl acetate (50 ml) and then dried. The solid was taken into RB flask, ethyl acetate (100 ml) was added and stirred at room temperature for about 6 hours. Solid was collected by filtration, washed with ethyl acetate and then dried. The solid was taken into RB flask, cooled to 0 ºC, acidified to pH 2.0 with 1N HCl, DCM was added, stirred for about 30 minutes. Organic layer was separated, and aqueous layer was extracted with DCM. The combined organic layer was washed with water (100 ml), brine solution (100 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained solid was stirred with hexane (100 ml) at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum to obtain the product (4 g, yield: 28.57%) as a solid. Enantiomeric purity by chiral HPLC: 94.67%. Intermediate 6: Preparation of (1S,3R)-3-((4- -2,2- dimethylcyclopropane-1-carboxylic acid: Step 1: Synthesis of Racemic 3-((4-chlorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (40 g, 285.42 mmol, 1.0 eq) in THF (400 ml) was added 4-chloroaniline (36.41 g, 285.42 mmol, 1.0 eq) and 4-methylbenzenesulfonic acid (5.4 g, 28.542 mmol, 0.1 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. Water (200 ml) was added to the reaction mixture, organic layer was separated, and the aqueous layer was extracted with DCM (3x400 ml). The combined organic layer was washed with water (500 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was treated with ethyl acetate (100 ml) and hexane (500 ml), stirred at room temperature for about 1 hour. Solid was filtered, washed with hexane (20 ml) and then dried under vacuum for about 15 minutes to obtain the title compound (60 g) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.11 (s, 1H), 10.19 (s, 1H), 7.58 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 9.0 Hz, 2H), 1.99 (d, J = 9.0 Hz, 1H), 1.88 (d, J = 9.5 Hz, 1H), 1.32 (s, 3H), 1.19 (s, 3H). ES-MS: m / z 290.13 (M+Na)+. Step 2: Synthesis of (1S,3R)-3-((4-chlorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxylic acid: A suspension of the Racemic 3-((4-chlorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Step 1, 20 g, 74.7 mmol, 1.0 eq) and Isopropanol (500 ml) was heated to reflux for about 1 hour to achieve a clear solution. (S)-phenylethyl amine (9.05 g, 74.7 mmol, 1.0 eq) was added to the reaction mixture and reflux was continued for about 3 hours. The reaction mixture was changed to room temperature and stirred for overnight. The solid was filtered, washed with Isopropanol (100 ml) and then dried under vacuum. The solid was taken into RB flask, isopropanol (300 ml) was added and stirred at room temperature for about 2 hours. Solid was filtered, washed with Isopropanol (100 ml) and then dried under vacuum. The wet solid was again taken into RB flask, Isopropanol (200 ml) was added, stirred, filtered and then dried under vacuum. The solid was acidified with 1N HCl to pH 2 and extracted with DCM (3x200 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (7.0 g) as a solid. ES-MS: m / z 268.18 (M+H)+. Intermediate 6a: -2,2- dimethylcyclopropane-1-carboxylic acid: A suspension of the Racemic 3-((4-chlorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 6-step 1, 10 g, 37.35 mmol, 1.0 eq) and Isopropanol (250 ml) was heated to reflux for about 1 hour to achieve a clear solution. (R)-phenylethyl amine (4.52 g, 37.35 mmol, 1.0 eq) was added to the reaction mixture and reflux was continued for about 3 hours. The reaction mixture was changed to room temperature and stirred for overnight. The solid was filtered, washed with Isopropanol (50 ml) and then dried under vacuum. The solid was taken into RB flask, isopropanol (150 ml) was added and stirred at room temperature for about 2 hours. Solid was filtered, washed with Isopropanol (50 ml) and then dried under vacuum. The wet solid was again taken into RB flask, Isopropanol (100 ml) was added, stirred at room temperature for about 2 hours. Solid was filtered, washed with Isopropanol (20 ml) and then dried under vacuum. DCM (180 ml) was added to the solid, acidified with 1N HCl to pH 2. Organic layer was separated, and the aqueous layer was extracted with DCM (3x100 ml). The combined organic layer was washed with water (100 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (2.1 g) as a solid. Enantiomeric purity by chiral HPLC: >99%. ES-MS: m / z 268.17 (M+H)+. Intermediate 7: of (1R,3S)-2,2-dimethyl-3-((5-methylisoxazol-3- yl)carbamoyl)cyclopropane-1-carboxylic acid: Step 1: Synthesis of Racemic 3-((benzyloxy)carbonyl)-2,2-dimethylcyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (50 g, 356.78 mmol, 1.0 eq) in Toluene (500 ml) was added pyridine (28 g, 356.78 mmol, 1.0 eq) and benzyl alcohol (38.5 g, 356.78 mmol, 1.0 eq). The reaction mixture was stirred at 80 ºC for about 5 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with water and extracted with ethyl acetate (1000 ml). The organic layer was washed with 1N HCl and water (1000 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Ethyl acetate (30 ml) and hexane (300 ml) were added to the crude compound, stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum to obtain the product (55 g, yield: 62%) as an off-white solid. Step 2: Synthesis of (1R,3S)-3-((benzyloxy)carbonyl)-2,2-dimethylcyclopropane-1-carboxylic acid: To a stirred solution of Racemic 3-((benzyloxy)carbonyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Step 1, 60 g, 241.76 mmol, 1.0 eq) in ethyl acetate (3000 ml) was added (R)-1-phenylethan-1-amine (29.29 g, 241.76 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was filtered and washed with ethyl acetate (100 ml). The solid was taken into round bottom flask, ethyl acetate (1000 ml) was added and stirred for about 2 hours. Solid was filtered and washed with ethyl acetate (100 ml). This procedure was repeated thrice with ethyl acetate (500 ml), finally filtered, washed with ethyl acetate (100 ml) and then dried under vacuum. The obtained solid was acidified with 1N HCl to pH = 2.0 and extracted with DCM (3x300 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (5.5 g) as a liquid. Enantiomeric purity by chiral HPLC: 99.6%. To a stirred solution of (1R,3S)-3-((benzyloxy)carbonyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Step 2, 4.0 g, 16.110 mmol, 1.0 eq) in DMF (40 ml) at 0 ºC was added potassium carbonate (4.4 g, 32.221 mmol, 2.0 eq) and methyl iodide (4.5 g, 32.22 mmol, 2.0 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Water (600 ml) was added to the reaction mixture and extracted with ethyl acetate (2x300 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient to obtain the title compound (3.0 g, yield: 71%) as an off-white solid.1H NMR (300 MHz, CDCl3): δ ppm 7.35-7.31 (m, 5H), 5.11 (ABq, JAB = 12.3 Hz, 2H), 3.61 (s, 3H), 1.92 (d, J = 9.1 Hz, 1H), 1.87 (d, J = 9.6 Hz, 1H), 1.40 (s, 3H), 1.19 (s, 3H); ES-MS: m / z 263.05 (M+H)+. Step 4: Synthesis of (1S,3R)-3-(methoxycarbonyl)-2,2-dimethylcyclopropane-1-carboxylic acid: To a suspension of 10% Pd / C (0.500 g) in methanol (30 ml) and ethyl acetate (30 ml) was added 1-benzyl 2-methyl (1S,2R)-3,3-dimethylcyclopropane-1,2-dicarboxylate (Step 3, 3.0 g, 11.450 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for overnight under hydrogen atmosphere. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite bed and washed with methanol and ethyl acetate (1:1, 300 ml). The filtrate was evaporated under reduced pressure to obtain the title compound (1.8 g, yield: 91%) as an off-white solid.1H NMR (300 MHz, CDCl3): δ ppm 3.73 (s, 3H), 1.99 (d, J = 8.7 Hz, 1H), 1.93 (d, J = 8.7 Hz, 1H), 1.37 (s, 3H), 1.28 (s, 3H); ES-MS: m / z 172.95 (M+H)+. Step 5: Synthesis of methyl (1R,3S)-2,2-dimethyl-3-((5-methylisoxazol-3- yl)carbamoyl)cyclopropane-1-carboxylate: To a stirred solution of (1S,3R)-3-(methoxycarbonyl)-2,2-dimethylcyclopropane- 1-carboxylic acid (Step 4, 1.8 g, 10.465 mmol, 1.0 eq) in DCM (18 ml) was added EDC.HCl (5 g, 26.162 mmol, 2.5 eq), 4-dimethylaminopyridine (0.766 g, 6.279 mmol, 0.6 eq) and 5- methylisoxazol-3-amine (1.0 g, 10.465 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (250 ml) and washed with water (2x200 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-4% methanol in dichloromethane gradient to obtain the title compound (0.800 g, yield: 30%) as an off-white solid.1H NMR (300 MHz, CDCl3): δ ppm 10.18 (s, 1H), 6.69 (s, 1H), 3.72 (s, 3H), 2.37 (s, 3H), 2.04 (d, J = 9.0 Hz, 1H), 1.94 (d, J = 9.0 Hz, 1H), 1.39 (s, 3H), 1.31 (s, 3H); ES-MS: m / z 252.95 (M+H)+. Step 6: Synthesis of (1R,3S)-2,2-dimethyl-3-((5-methylisoxazol-3- To a stirred solution of methyl (1R,3S)-2,2-dimethyl-3-((5-methylisoxazol-3- yl)carbamoyl)cyclopropane-1-carboxylate (Step 5, 0.800 g, 3.174 mmol, 1.0 eq) in methanol (8 ml) and THF (8 ml) was added 1.0M KOH solution (1.3 g in 23.8 ml water, 23.809 mmol, 7.5 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The residue was acidified with 1N HCl to pH 4.0 and was extracted with DCM (2x100 ml). The combined organic layer was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound (0.700 g) was used as such for next step without further purification.1H NMR (300 MHz, DMSO-d6): δ ppm 12.10 (s, 1H), 10.98 (s, 1H), 6.59 (d, J = 4.8 Hz, 1H), 2.34 (s, 3H), 2.02 (d, 1H), 1.88 (d, 1H), 1.29 (s, 3H), 1.16 (s, 3H); ES-MS: m / z 239.08 (M+H)+. Intermediate 8: Preparation of (1S,3R)-2,2-dimethyl-3-((5-methylisoxazol-3- yl)carbamoyl)cyclopropane-1-carboxylic acid: Step 1: Synthesis of (1S,3R)-3-((benzyloxy)carbonyl)-2,2-dimethylcyclopropane-1-carboxylic acid: To a stirred solution of Racemic 3-((benzyloxy)carbonyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 7-step 1, 55 g, 221.52 mmol, 1.0 eq) in ethyl acetate (1500 ml) was added (S)-1-phenylethan-1-amine (26.8 g, 221.52 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for overnight. Solid was filtered and washed with ethyl acetate (200 ml). The wet solid was taken into round bottom flask, ethyl acetate (800 ml) was added and stirred for about 3 hours. Solid was filtered and washed with ethyl acetate (150 ml). This procedure was repeated thrice with ethyl acetate (500 ml, 300 ml and 150 ml), finally, filtered and then dried under vacuum. The obtained solid was acidified with 1N HCl to pH = 2.0 and extracted with DCM (3x100 ml). The combined organic layer was washed with water (100 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (6.0 g) as a liquid. enantiomeric purity by chiral HPLC: 99.93%;1H NMR (300 MHz, DMSO-d6): δ ppm 12.24 (s, 1H), 7.37-7.31 (m, 5H), 5.06 (ABq, JAB = 12.6 Hz, 2H), 2.01 (d, 1H), 1.94 (d, 1H), 1.31 (s, 3H), 1.14 (s, 3H); ES-MS: m / z 249.28 (M+H)+. To a stirred solution of (1S,3R)-3-((benzyloxy)carbonyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Step 1, 4.0 g, 16.110 mmol, 1.0 eq) in DMF (40 ml) at 0 ºC was added potassium carbonate (4.5 g, 32.221 mmol, 2.0 eq) and methyl iodide (4.4 g, 32.221 mmol, 2.0 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ice water (600 ml) and extracted with ethyl acetate (2x300 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient to obtain the title compound (3.5 g, yield: 83%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 7.38- 7.33 (m, 5H), 5.16 (d, J = 12.0 Hz, 1H), 5.12 (d, J = 12.5 Hz, 1H), 3.65 (s, 3H), 1.95 (d, J = 9.5 Hz, 1H), 1.90 (d, J = 9.5 Hz, 1H), 1.43 (s, 3H), 1.22 (s, 3H); ES-MS: m / z 285.43 (M+Na)+. Step 3: Synthesis of (1R,3S)-3-(methoxycarbonyl)-2,2-dimethylcyclopropane-1-carboxylic acid: To a stirred solution of enantiopure 1-benzyl 2-methyl (1R,2S)-3,3- dimethylcyclopropane-1,2-dicarboxylate (Step 2, 3.5 g, 13.358 mmol, 1.0 eq) in methanol and ethyl acetate (70 ml, 1:1) was added Pd / C (0.660 g). The reaction mixture was stirred at room temperature under hydrogen atmosphere for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite bed and washed with EtOAc and methanol (300 ml, 1:1). The filtrate was evaporated under reduced pressure to obtain the title compound (2.2 g, yield: 96%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 3.72 (s, 3H), 1.97 (d, J = 9.0 Hz, 1H), 1.93 (d, J = 9.0 Hz, 1H), 1.39 (s, 3H), 1.26 (s, 3H); ES-MS: m / z 173.40 (M+H)+. Step 4: Synthesis of methyl (1S,3R)-2,2-dimethyl-3-((5-methylisoxazol-3- To a stirred solution of (1R,3S)-3-(methoxycarbonyl)-2,2-dimethylcyclopropane- 1-carboxylic acid (Step 3, 1.1 g, 6.395 mmol, 1.0 eq) in DCM (10 ml) was added EDC.HCl (3.0 g, 15.988 mmol, 2.5 eq), 4-dimethylaminopyridine (0.468 g, 3.837 mmol, 0.6 eq) and 5- methylisoxazol-3-amine (0.627 g, 6.395 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (200 ml) and washed with water (200 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-4% methanol in dichloromethane gradient to obtain the title compound (0.800 g, yield: 49.6%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 10.0 (s, 1H), 6.7 (s, 1H), 3.75 (s, 3H), 2.41 (s, 3H), 2.05 (d, 1H), 1.95 (d, 1H), 1.40 (s, 3H), 1.35 (s, 3H); ES-MS: m / z 253.49 (M+H)+. Step 5: Synthesis of (1S,3R)-2,2-dimethyl-3-((5-methylisoxazol-3- To a stirred solution of methyl (1S,3R)-2,2-dimethyl-3-((5-methylisoxazol-3- yl)carbamoyl)cyclopropane-1-carboxylate (Step 4, 0.800 g, 3.174 mmol, 1.0 eq) in Methanol and THF (1:1, 16 ml) was added 1M KOH solution (23 ml, 23.809 mmol, 7.5 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The reaction mixture was acidified with 1N HCl and extracted with DCM (2x100 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound (0.700 g) was used as such for next step without further purification.1H NMR (500 MHz, CDCl3): δ ppm 10.82 (s, 1H), 6.76 (s, 1H), 2.44 (s, 3H), 2.21 (d, J = 8.0 Hz, 1H), 2.09 (d, J = 8.0 Hz, 1H), 1.42 (s, 3H), 1.40 (s, 3H); ES-MS: m / z 239.4 (M+H)+. Intermediate 9: Preparation of 3-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline: To a stirred solution of 4-chloro-6,7-dimethoxyquinoline (2 g, 8.942 mmol, 1.0 eq) in N,N-dimethylacetamide (20 ml) was added sodium tert-butoxide (2.1 g, 22.355 mmol, 2.5 eq) and 4-amino-2-chlorophenol (2.5 g, 17.884 mmol, 2.0 eq). The reaction mixture was stirred at 110 ºC for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was allowed to room temperature, water (100 ml) was added and extracted with ethyl acetate (100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-80% ethyl acetate in hexanes gradient to obtain the product (1.5 g, yield: 50.8%) as a brown colour solid.1H NMR (300 MHz, CDCl3): δ ppm 8.47 (d, J = 5.4 Hz, 1H), 7.61 (s, 1H), 7.42 (s, 1H), 7.04 (d, J = 8.7 Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.65 (dd, J = 8.7, 2.7 Hz, 1H), 6.32 (d, J = 5.1 Hz, 1H), 4.07 (s, 3H), 4.04 (s, 2H), 3.49 (s, 3H); ES-MS: m / z 331.07 (M+H)+. Intermediate 10: Preparation of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline: Method 1: To a stirred solution of 4-chloro-6,7-dimethoxyquinoline (5 g, 22.355 mmol, 1.0 eq) in DMF (100 ml) was added 4-amino-2-fluorophenol (5.68 g, 44.710 mmol, 2.0 eq) and sodium tert-butoxide (6.445 g, 67.06 mmol, 3.0 eq). The reaction mixture was heated at 120 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with water (1000 ml) and extracted with ethyl acetate (3x500 ml). The combined organic layer was evaporated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to obtain the title compound (5.5 g, yield: 78.28%) as a black colour solid.1H NMR (300 MHz, CDCl3): δ ppm 8.48 (d, J = 5.1 Hz, 1H), 7.59 (s, 1H), 7.42 (s, 1H), 7.03 (t, J = 8.4 Hz, 1H), 6.59-6.51 (m, 2H), 6.49-6.40 (m, 1H), 4.06 (s, 3H), 4.04 (s, 3H), 3.82 (s, 2H); ES-MS: m / z 315.31 (M+H)+. Method 2: Step 1: Synthesis of 4-(2-fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline: To a suspension of 4-Chloro-6,7-dimethoxyquinoline (30 g, 134.16 mmol, 1.0 eq) in N-methyl-2-pyrrolidone (180 ml) was added N-ethyl-N-isopropylpropan-2-amine (81.76 ml, 469.46 mmol, 3.5 eq) and 2-Fluoro-4-nitrophenol (35.82 g, 228.02 mmol, 1.7 eq). The reaction mass was stirred at 140-150 °C for overnight. TLC indicated starting material was consumed and the desired product was observed. The heating bath was removed, and the reaction mass was allowed to reach room temperature. Reaction mass was cooled to 10-20 °C, water (1800 ml) was added, stirred at same temperature for about 2 hours. Solid was filtered, washed with water (180 ml) and then dried under vacuum. Again, water (1800 ml) was added to the wet solid, stirred at 10-20 °C for around 1 hour. Solid was filtered, washed with water (180 ml) and then dried under vacuum. Methanol (210 ml) was added to the resulting solid, refluxed for around 1 hour. Heating bath was removed, and the reaction mass was stirred at room temperature for around 4 hours. Solid was filtered, washed with methanol (30 ml) and then dried under vacuum to obtain the product (31.4 g, yield: 68%) as a pale- yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.57 (d, J = 5.5 Hz, 1H), 8.45 (dd, J = 10.5, 2.5 Hz, 1H), 8.21-8.18 (m, 1H), 7.61 (t, J = 9.0 Hz, 1H), 7.45 (s, 2H), 6.78 (d, J = 5.0 Hz, 1H), 3.96 (s, 3H), 3.92 (s, 3H); ES-MS: m / z 345.08 (M+H)+. Step 2: Synthesis of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline: To a suspension of 4-(2-fluoro-4-nitrophenoxy)-6,7-dimethoxyquinoline (Step 1, 30 g, 87.13 mmol, 1.0 eq) in Methanol (150 ml) and water (30 ml) was added Iron powder (24.33 g, 435.66 mmol, 5.0 eq). Acetic acid (36 ml) was added slowly over a period of 30 minutes. The reaction mixture was stirred at 60-65oC for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. The heating bath was removed, and the reaction mass was allowed to reach room temperature. Ethyl acetate (300 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. The reaction mass was filtered through celite bed, washed with ethyl acetate (300 ml). Filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution, stirred at room temperature for about 30 minutes. Organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2x150 ml). The combined organic layer was washed with water (300 ml) and brine solution (150 ml). Organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure. Methanol (90 ml) was added to the obtained solid, stirred at room temperature for about 30 minutes. Solid was filtered, washed with methanol (30 ml) and then dried under vacuum at 50-60 °C for about 2 hours to afford the title compound (21.36 g, yield: 78%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.45 (d, J = 5.0 Hz, 1H), 7.50 (s, 1H), 7.38 (s, 1H), 7.07 (t, J = 9.0 Hz, 1H), 6.55 (dd, J = 13.5, 2.5 Hz, 1H), 6.46 (dd, J = 8.5, 2.0 Hz, 1H), 6.39 (d, J = 5.0 Hz, 1H), 5.48 (s, 2H), 3.94 (s, 6H); ES-MS: m / z 315.09 (M+H)+. Intermediate 11: Preparation of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluoroaniline: To a stirred solution of 4-chloro-6,7-dimethoxyquinoline (10 g, 44.71 mmol, 1.0 eq) in DMF (100 ml) was added sodium tert-butoxide (21.5 g, 223.55 mmol, 5.0 eq) and 4-amino- 3-fluorophenol (11.3 g, 89.42 mmol, 2.0 eq). The reaction mixture was stirred at 120 ºC for about 48 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was allowed to room temperature, quenched with ice water (2000 ml) and extracted with ethyl acetate (2x500 ml). The combined organic layer was washed with water (2x500 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-80% ethyl acetate in hexane gradient to obtain the title compound (0.500 g) as a solid.1H NMR (300 MHz, CDCl3): δ ppm 8.48 (d, J = 5.1 Hz, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 6.92- 6.83 (m, 3H), 6.45 (d, J = 5.4 Hz, 1H), 4.05 (s, 6H), 3.76 (s, 2H); APCI-MS: m / z 315.1 (M+H)+. Intermediate 12: Preparation of 4-((6,7- 4-yl)oxy)-2-methylaniline: To a stirred solution of 4-chloro-6,7-dimethoxyquinoline (5 g, 22.355 mmol, 1.0 eq) in DMF (100 ml) was added 4-amino-3-methylphenol (5.506 g, 44.710 mmol, 2.0 eq) and sodium tert-butoxide (6.445 g, 67.06 mmol, 3.0 eq). The reaction mixture was heated at 100 ºC for about 36 hours. The reaction mixture was diluted with water (700 ml) and extracted with ethyl acetate (3x200 ml). The combined organic layer was washed with water (500 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to obtain the title compound (3.30 g, yield: 47.6%) as a black colour solid.1H NMR (300 MHz, CDCl3): δ ppm 8.45 (d, J = 5.4 Hz, 1H), 7.58 (s, 1H), 7.41 (s, 1H), 6.90-6.85 (m, 2H), 6.74 (d, J = 8.4 Hz, 1H), 6.43 (d, J = 5.4 Hz, 1H), 4.05 (s, 3H), 4.04 (s, 3H), 3.66 (s, 2H), 2.20 (s, 3H); ES-MS: m / z 311.47 (M+H)+. Intermediate 13: Preparation of 2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline: To a stirred solution of 4-chloro-6,7-dimethoxyquinoline (5 g, 22.35 mmol, 1.0 eq) in DMF (50 ml) was added potassium tert-butoxide (7.52 g, 67.05 mmol, 3.0 eq) and 4-amino- 3-chlorophenol (6.41 g, 44.71 mmol, 2.0 eq). The reaction mixture was stirred at 110-120 ºC for about 48 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was cooled to room temperature, reaction mixture poured into water (500 ml) and extracted with ethyl acetate (3x100 ml). The combined organic layer was washed with water (100 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient. The obtained compound was treated with hexane (15 ml), filtered and then dried under vacuum to obtain the title compound (2.8 g, yield: 37.8%) as a solid.1H NMR (300 MHz, CDCl3): δ ppm 8.48 (d, J = 5.4 Hz, 1H), 7.54 (s, 1H), 7.42 (s, 1H), 7.15 (d, J = 2.4 Hz, 1H), 6.94 (dd, J = 8.7, 2.4 Hz, 1H), 6.84 (d, J = 8.7 Hz, 1H), 6.44 (d, J = 5.4 Hz, 1H), 4.04 (s, 6H); ES-MS: m / z 330.95 (M+H)+. Intermediate 14: Preparation of 3-fluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4- yl)oxy)aniline: Step 1: Synthesis of 2-(benzyloxy)-1-methoxy-4-nitrobenzene: To a stirred solution of 2-methoxy-5-nitrophenol (20 g, 118.25 mmol, 1.0 eq) in DMF (300 ml) was added potassium carbonate (49 g, 354.7 mmol, 3.0 eq) followed by benzyl bromide (18.19 g, 106.42 mmol, 0.9 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was poured into ice water and stirred for about 1 hour. Solid was collected by filtration, washed with water (2000 ml) and then dried under vacuum to obtain the title compound (26 g) as a solid.1H NMR (300 MHz, CDCl3): δ ppm 7.91 (dd, J = 8.7, 2.4 Hz, 1H), 7.80 (d, J = 2.4 Hz, 1H), 7.48-7.39 (m, 2H), 7.37-7.31 (m, 3H), 6.92 (d, J = 9.0 Hz, 1H), 5.20 (s, 2H), 3.97 (s, 3H); ES-MS: m / z 281.97 (M+Na)+. Step 2: Synthesis of 3-(benzyloxy)-4-methoxyaniline: To a stirred solution of 2-(benzyloxy)-1-methoxy-4-nitrobenzene (Step 1, 21.0 g, 80.99 mmol, 1.0 eq) in ethanol (500 ml) and water (100 ml) was added Iron powder (18 g, 323.42 mmol, 4.0 eq) and acetic acid (4.2 ml). The reaction mixture was heated at 80 ºC for about 5 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was allowed to room temperature, DCM (200 ml) was added, filtered through celite bed and washed with DCM. The filtrate was basified with saturated aqueous sodium bicarbonate solution, organic layer was separated, and aqueous layer was extracted with DCM (2x200 ml). The combined organic layer was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was washed with hexane and then dried under vacuum to obtain the title compound (17.0 g) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.43-7.37 (m, 4H), 7.33-7.30 (m, 1H), 6.67 (d, J = 8.5 Hz, 1H), 6.34 (d, J = 2.5 Hz, 1H), 6.09 (dd, J = 8.5, 2.5 Hz, 1H), 4.97 (s, 2H), 4.65 (s, 2H), 3.62 (s, 3H); ES-MS: m / z 230.21 (M+H)+. Step 3: Synthesis of 5-(((3-(benzyloxy)-4-methoxyphenyl)amino)methylene)-2,2-dimethyl-1,3- dioxane-4,6-dione: Method 1: To a stirred solution of 3-(benzyloxy)-4-methoxyaniline (Step 2, 9.0 g, 39.267 mmol, 1.0 eq) in ethanol (90 ml) was added trimethyl orthoformate (20.83 g, 196.33 mmol, 5.0 eq) and 2,2-dimethyl-1,3-dioxane-4,6-dione (7.07 g, 49.08 mmol, 1.25 eq). The reaction mixture was heated to reflux for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. Water (100 ml) was added to the reaction mixture, the precipitate formed was collected by filtration and dried in vacuo. The obtained compound (12 g) was used as such for next step without further purification.1H NMR (500 MHz, DMSO- d6): δ ppm 11.22 (d, J = 15.0 Hz, 1H), 8.55 (d, J = 15.0 Hz, 1H), 7.47-7.35 (m, 6H), 7.10 (dd, J = 8.5, 2.5 Hz, 1H), 7.01 (d, J = 8.5 Hz, 1H), 5.14 (s, 2H), 3.77 (s, 3H), 1.67 (s, 6H); ES- API: m / z 382.1 (M-H)-. Method 2: To a stirred solution of 3-(benzyloxy)-4-methoxyaniline (70 g, 305.27 mmol, 1.0 eq) in Isopropanol (280 ml) was added 5-(methoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6- dione (73.89 g, 396.86 mmol, 1.3 eq). The reaction mixture was refluxed for around 3 hours. TLC indicated starting material was consumed and the desired product was observed. The heating bath was removed, and the reaction mass was allowed to reach room temperature. Reaction mass was cooled to 0-10 °C, stirred for around 1 hour. Solid was filtered, washed with isopropanol (350 ml) and then dried under vacuum to obtain the product (105.2 g, yield: 89.9%) as a yellow solid. Step 4: Synthesis of 7-(benzyloxy)-6-methoxyquinolin-4-ol: A solution of 5-(((3-(benzyloxy)-4-methoxyphenyl)amino)methylene)-2,2- dimethyl-1,3-dioxane-4,6-dione (Step 3, 12 g, 31.298 mmol, 1.0 eq) and diphenylether (60 ml) was heated at 210 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was allowed to room temperature, Hexane (100 ml) was added to the reaction mixture, solid was collected by filtration and dried under vacuum to obtain the title compound (8.7 g, yield: 98.97%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.757 (dd, J = 7.0, 6.0 Hz, 1H), 7.50-7.35 (m, 5H), 7.14 (t, J = 7.5 Hz, 1H), 7.0 (dd, J = 9.0, 1.0 Hz, 1H), 5.93 (d, J = 6.5 Hz, 1H), 5.18 (s, 2H), 3.83 (s, 3H); ES-API: m / z 280.1 (M-H)-. Step 5: Synthesis of 7-(benzyloxy)-4-chloro-6-methoxyquinoline: To a stirred solution of 7-(benzyloxy)-6-methoxyquinolin-4-ol (Step 4, 7.5 g, 26.690 mmol, 1.0 eq) in N,N-dimethylformamide (75 ml) and acetonitrile (75 ml) was added POCl3 (20 g, 133.45 mmol, 5.0 eq) dropwise. The reaction mixture was stirred at 80 ºC for about 6 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was cooled to room temperature, POCl3 was evaporated under vacuum, basified with saturated sodium carbonate solution and extracted with ethyl acetate (2x500 ml). The combined organic layer was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was stirred with hexane (500 ml), solid was filtered and then dried under vacuum to obtain the title compound (4.5 g, yield: 56.3%) as a brown colour solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.61 (d, J = 4.5 Hz, 1H), 7.57-7.51 (m, 4H), 7.44-7.35 (m, 4H), 5.32 (s, 2H), 3.98 (s, 3H); ES-MS: m / z 299.77 (M+H)+. Step 6: Synthesis of 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinoline: Method 1: To a stirred solution of 7-(benzyloxy)-4-chloro-6-methoxyquinoline (Step 5, 4 g, 13.356 mmol, 1.0 eq) in diphenylether (60 ml) was added potassium carbonate (7.38 g, 53.42 mmol, 4.0 eq) and 2-fluoro-4-nitrophenol (3.144 g, 20.033 mmol, 1.5 eq). The reaction mixture was stirred at 180 ºC for about 8 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was cooled to 0 ºC, hexane (500 ml) was added and stirred at room temperature for about 2 hours. The solid formed was collected by filtration, washed with hexane and dried. The obtained solid was dissolved in DCM (100 ml) and washed with water (100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (2 g, yield: 35%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 8.485 (d, J = 5.0 Hz, 1H), 8.11 (dd, J = 10.0, 2.5 Hz, 1H), 8.07-8.04 (m, 1H), 7.45-7.43 (m, 3H), 7.38 (s, 1H), 7.32 (t, J = 7.5 Hz, 2H), 7.26 (dd, J = 8.5, 8.0 Hz, 2H), 6.47 (d, J = 5.0 Hz, 1H), 5.26 (s, 2H), 3.96 (s, 3H). Method 2: To a solution of 7-(benzyloxy)-4-chloro-6-methoxyquinoline (34 g, 113.41 mmol, 1.0 eq) in N-methyl-2-pyrrolidone (340 ml) was added N-ethyl-N-isopropylpropan-2-amine (69.13 ml, 396.93 mmol, 3.5 eq) and 2-Fluoro-4-nitrophenol (26.72 g, 170.11 mmol, 1.5 eq). The reaction mass was stirred at 140-150 °C for around 7 hours. TLC indicated starting material was consumed and the desired product was observed. The heating bath was removed, and the reaction mass was allowed to reach room temperature. Reaction mass was cooled to 10-20 °C, water (4.8 Ltr) added, stirred at same temperature for about 1 hour. Solid was filtered, washed with water (170 ml) and then dried under vacuum. Again, water (1000 ml) was added to the wet solid, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (170 ml) and then dried under vacuum to obtain the product (38.5 g, yield: 80.74%) as a pale-yellow solid. Step 7: Synthesis of 4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-ol: Method 1: To a stirred solution of 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-6- methoxyquinoline (Step 6, 2 g, 4.757 mmol, 1.0 eq) in Trifluoroacetic acid (20 ml) was added methane sulfonic acid (0.914 g, 9.514 mmol, 2.0 eq). The reaction mixture was stirred at 80 ºC for about 5 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure to remove trifluoroacetic acid and neutralized with 1N NaOH solution. Solid was filtered and then dried under vacuum to obtain the title compound (1.4 g, yield: 89%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.54 (d, J = 2.0 Hz, 1H), 8.57 (d, J = 5.0 Hz, 1H), 8.47 (dd, J = 10.5, 2.5 Hz, 1H), 8.22 (dt, J = 9.0, 1.0 Hz, 1H), 7.64 (t, J = 8.5 Hz, 1H), 7.48 (s, 1H), 7.37 (s, 1H), 6.78 (d, J = 5.5 Hz, 1H), 3.95 (s, 3H); ES-MS: m / z 330.78 (M+H)+. Method 2: To a solution of 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinoline (Step 6, 20 g, 47.57 mmol, 1.0 eq) in trifluoroacetic acid (100 ml) was added methane sulfonic acid (9.18 g, 6 ml, 95.14 mmol, 2.0 eq). The reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure. The resulting compound was neutralized with saturated sodium bicarbonate solution, stirred for about 1 hour. Solid was filtered, washed with water and then dried under vacuum. Solid was treated with Methyl- tert-butyl ether and Hexanes (1:1, 200 ml), stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum. The obtained compound was further purified by column chromatography using 0-4% methanol in dichloromethane gradient to obtain the product (14 g, yield: 89%) as a solid. Step 8: Synthesis of 4-(3-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)morpholine: To a stirred solution of 4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-ol (Step 7, 1.4 g, 4.242 mmol, 1.0 eq) in acetonitrile (175 ml) was added Cesium carbonate (4.13 g, 12.675 mmol, 3.0 eq) and potassium iodide (0.210 g, 1.264 mmol, 0.3 eq). The reaction mixture was stirred at room temperature for about 20 minutes, 4-(3-chloropropyl)morpholine (0.927 g, 5.69 mmol, 1.35 eq) was added and the reaction mixture was stirred at 85 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated in vacuo, diluted with DCM (300 ml) and washed with water (300 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to obtain the title compound (1.1 g, yield: 58%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.57 (d, J = 5.0 Hz, 1H), 8.46 (dd, J = 10.0, 2.5 Hz, 1H), 8.20 (d, J = 9.0 Hz, 1H), 7.61 (t, J = 8.5 Hz, 1H), 7.45 (s, 2H), 6.78 (d, J = 5.0 Hz, 1H), 4.21 (t, J = 6.0 Hz, 2H), 3.92 (s, 3H), 3.59 (m, 4H), 2.41 (m, 6H), 1.98 (t, J = 5.5 Hz, 2H); ES-MS: m / z 457.73 (M+H)+. Step 9: Synthesis of 3-fluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4- yl)oxy)aniline: To a stirred solution of 4-(3-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)morpholine (Step 8, 1.1 g, 2.404 mmol, 1.0 eq) in methanol (20 ml) and ethyl acetate (20 ml) was added 10% Pd / C (0.300 g). The reaction mixture was stirred under hydrogen atmosphere at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite bed, washed with methanol and ethyl acetate. The filtrate was concentrated under reduced pressure to obtain the title compound (0.800 g, yield: 80%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.44 (d, J = 5.5 Hz, 1H), 7.50 (s, 1H), 7.37 (s, 1H), 7.06 (t, J = 9.0 Hz, 1H), 6.55 (dd, J = 13.0, 2.5 Hz, 1H), 6.46 (dd, J = 8.5, 2.5 Hz, 1H), 6.38 (d, J = 5.0 Hz, 1H), 5.48 (s, 2H), 4.19 (t, J = 6.0 Hz, 2H), 3.94 (s, 3H), 3.59 (t, J = 4.5 Hz, 4H), 2.50 (m, 2H), 2.41-2.39 (m, 4H), 1.97 (t, J = 7.0 Hz, 2H). Intermediate 15: Preparation of 3-fluoro-4-((7-methoxy-6-(3-morpholinopropoxy)quinolin-4- yl)oxy)aniline: Step 1: Synthesis of 2-methoxy-4-nitrophenyl acetate: To a stirred solution of 2-methoxy-4-nitrophenol (30 g, 177.3 mmol, 1.0 eq) in DCM (300 ml) at 0 ºC was added pyridine (15.72 ml, 195.03 mmol, 1.1 eq) and acetic anhydride (18.4 ml, 195.03 mmol, 1.1 eq). The reaction mixture was stirred at room temperature for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml), washed with saturated sodium bicarbonate solution and water (50 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 20% ethyl acetate in hexanes eluent to obtain the title compound (30 g, yield: 80.17%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 7.90 (dd, J = 9.0, 2.5 Hz, 1H), 7.86 (d, J = 2.5 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 3.95 (s, 3H), 2.37 (s, 3H). Step 2: Synthesis of 4-amino-2-methoxyphenyl acetate: To a suspension of 10% Pd / C (2.5 g) in ethanol (200 ml) was added 2-methoxy-4- nitrophenyl acetate (Step 1, 20 g, 96.187 mmol, 1.0 eq). The reaction mixture was stirred at room temperature under hydrogen balloon pressure for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethanol (200 ml), filtered through celite pad and washed with ethanol (200 ml). The filtrate was evaporated, and the obtained compound (15 g) was used as such for next step without further purification.1H NMR (500 MHz, CDCl3): δ ppm 6.81 (d, J = 8.5 Hz, 1H), 6.31 (d, J = 2.5 Hz, 1H), 6.24 (dd, J = 8.5, 2.5 Hz, 1H), 3.78 (s, 3H), 2.29 (s, 3H); ES-MS: m / z 181.66 (M+H)+. Step 3: Synthesis of 5-(methoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione: A solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (15 g, 104.07 mmol, 1.0 eq) and trimethyl orthoformate (34.15 ml, 312.25 mmol, 3.0 eq) were heated at 80 ºC for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. Hexane was added to the residue, stirred for about 30 minutes. Solid was collected by filtration and then dried under vacuum to obtain the desired compound (15 g) as an off-white solid. Step 4: Synthesis of 4-(((2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methyl)amino)-2- methoxyphenyl acetate: To a stirred solution of 4-amino-2-methoxyphenyl acetate (Step 2, 15 g, 82.78 mmol, 1.0 eq) in ethanol (150 ml) was added 5-(methoxymethylene)-2,2-dimethyl-1,3-dioxane-4,6- dione (Step 3, 15.24 g, 82.78 mmol, 1.0 eq). The reaction mixture was refluxed for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. Water (100 ml) was added to the reaction mixture, solid formed was filtered, washed with water and then dried under vacuum to obtain the title compound (16 g, yield: 59.27%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 11.26 (d, J = 14.5 Hz, 1H), 8.62 (d, J = 14.5 Hz, 1H) 7.44 (s, 1H), 7.13 (s, 2H), 3.82 (s, 3H), 2.25 (s, 3H), 1.67 (s, 6H); ES-MS: m / z 333.85 (M-H)-. Step 5: Synthesis of 7-methoxy-4-oxo-1,4-dihydroquinolin-6-yl acetate: A solution of 4-(((2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methyl)amino)-2- methoxyphenyl acetate (Step 4, 16 g, 47.71 mmol, 1.0 eq) and diphenyl ether (80 ml) were heated at 210 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was allowed to room temperature, hexane (200 ml) was added to the reaction mixture, solid formed was collected by filtration and then dried under vacuum to obtain the title compound (9.0 g, yield: 81.08%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 11.64 (s, 1H), 7.86-7.83 (m, 1H), 7.68 (s, 1H), 7.06 (s, 1H), 5.96 (d, J = 7.5 Hz, 1H), 3.86 (s, 3H), 2.28 (s, 3H). Step 6: Synthesis of 4-chloro-7-methoxyquinolin-6-yl acetate: To a stirred solution of 7-methoxy-4-oxo-1,4-dihydroquinolin-6-yl acetate (Step 5, 12 g, 51.502 mmol. 1.0 eq) in chloroform (200 ml) at 0 ºC was added POCl3 (24 ml, 257.51 mmol, 5.0 eq). The reaction mixture was heated to reflux for about 6 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated in vacuo, basified with saturated sodium bicarbonate solution and extracted with DCM (2x50 ml). The organic layer was separated, dried over sodium sulphate, filtered and concentrated in vacuo. The crude compound was purified by silica gel column chromatography using 1% methanol in DCM as an eluent to afford the title compound (7.2 g, yield: 55.55%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.78 (d, J = 5.0 Hz, 1H), 7.90 (s, 1H), 7.65 (d, J = 5.0 Hz, 1H), 7.64 (s, 1H), 3.97 (s, 3H), 2.35 (s, 3H); ES- MS: m / z 251.83 (M+H)+. Step 7: Synthesis of 4-chloro-7-methoxyquinolin-6-ol: To a stirred solution of 4-chloro-7-methoxyquinolin-6-yl acetate (Step 6, 7.2 g, 28.608 mmol, 1.0 eq) in ethanol (61.7 ml) was added sodium hydroxide (1.25 g, 31.469 mmol, 1.1 eq) and water (10.28 ml). The reaction mixture was stirred at room temperature for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was cooled to 0 ºC, neutralized with 1N HCl. Solid was filtered and then dried under vacuum to afford the title compound (5.89 g, yield: 98.33%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.38 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 7.49 (d, J = 5.0 Hz, 1H), 7.41 (d, J = 9.0 Hz, 2H), 3.96 (s, 3H); ES-MS: m / z 209.85 (M+H)+. Step 8: Synthesis of 4-(3-((4-chloro-7-methoxyquinolin-6-yl)oxy)propyl)morpholine: To a stirred solution of 4-chloro-7-methoxyquinolin-6-ol (Step 7, 5 g, 23.85 mmol, 1.0 eq) in DMF (50 ml) was added 4-(3-chloropropyl)morpholine (4.69 ml, 31.0 mmol, 1.3 eq) and potassium carbonate (9.8 g, 71.55 mmol, 3.0 eq). The reaction mixture was heated at 100 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. Water (200 ml) was added to the reaction mixture and extracted with ethyl acetate (2x50 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 20% ethyl acetate in hexanes eluent to afford the title compound (4 g, yield: 50%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.61 (d, J = 5.0 Hz, 1H), 7.55 (d, J = 5.0 Hz, 1H), 7.45 (s, 1H), 7.37 (s, 1H), 4.20 (t, J = 6.5 Hz, 2H), 3.96 (s, 3H), 3.58 (t, J = 4.5 Hz, 4H), 2.46 (t, J = 7.0 Hz, 2H), 2.38 (m, 4H), 2.01- 1.95 (m, 2H); ES-MS: m / z 336.99 (M+H)+. Step 9: Synthesis of 4-(3-((4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)morpholine: To a stirred solution of 4-(3-((4-chloro-7-methoxyquinolin-6- yl)oxy)propyl)morpholine (Step 8, 2 g, 5.937 mmol, 1.0 eq) in diphenyl ether (10 ml) was added 2-fluoro-4-nitrophenol (1.399 g, 8.906 mmol, 1.5 eq) and potassium carbonate (3.28 g, 23.74 mmol, 4.0 eq). The reaction mixture was heated at 170 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. Hexane (50 ml) was added to the reaction mixture, solid formed was collected by filtration and dried. The obtained solid was dissolved in DCM (100 ml) and washed with water (50 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 1% methanol in dichloromethane eluent to afford the title compound (2.1 g, yield: 77.49%) as a yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.57 (d, J = 5.0 Hz, 1H), 8.46 (dd, J = 10.5, 2.5 Hz, 1H), 8.21-8.18 (m, 1H), 7.61 (t, J = 8.5 Hz, 1H), 7.45 (d, J = 6.0 Hz, 2H), 6.78 (d, J = 5.0 Hz, 1H), 4.16 (t, J = 6.5 Hz, 2H), 3.96 (s, 3H), 3.55 (t, J = 5.0 Hz, 4H), 2.43 (t, J = 7.0 Hz, 2H), 2.35 (m, 4H), 1.97-1.93 (m, 2H); ES-MS: m / z 457.94 (M+H)+. Step 10: Synthesis of 3-fluoro-4-((7-methoxy-6-(3-morpholinopropoxy)quinolin-4- yl)oxy)aniline: To a stirred solution of 4-(3-((4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)morpholine (Step 9, 2.1 g, 4.59 mmol, 1.0 eq) in ethanol (42 ml) was added Iron powder (1.025 g, 18.362 mmol, 8.0 eq), acetic acid (0.374 g, 6.24 mmol, 2.72 eq) and water (8.4 ml). The reaction mixture was refluxed for about 8 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethanol (50 ml) and filtered through celite pad. The filtrate was evaporated, basified with saturated sodium bicarbonate solution and extracted with DCM (2x50 ml). The combined organic layer was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 2% methanol in DCM to afford the title compound (1.5 g, yield:76.53%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.45 (d, J = 5.0 Hz, 1H), 7.50 (s, 1H), 7.38 (s, 1H), 7.07 (t, J = 9.0 Hz, 1H), 6.55 (dd, J = 13.5, 2.5 Hz, 1H), 6.47 (dd, J = 9.0, 2.5 Hz, 1H), 6.39 (d, J = 5.0 Hz, 1H), 5.48 (s, 2H), 4.18 (t, J = 6.5 Hz, 2H), 3.94 (s, 3H), 3.56 (t, J = 4.5 Hz, 4H), 2.46 (t, J = 7.0 Hz, 2H), 2.38 (m, 4H), 1.99-1.94 (m, 2H); ES-MS: m / z 428.07 (M+H)+. Intermediate 16: Preparation of 4-((7-(benzyloxy)-6-methoxyquinolin-4-yl)oxy)-3- fluoroaniline: To a stirred solution of 7-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-6- methoxyquinoline (Intermediate 14-step 6, 1.5 g, 3.568 mmol, 1.0 eq) in ethanol (30 ml) and water (6 ml) was added Iron powder (0.797 g, 14.27 mmol, 4.0 eq) and acetic acid (0.3 ml). The reaction mixture was stirred at 80 ºC for about 6 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite bed and washed with ethyl acetate. The filtrate was evaporated under reduced pressure, basified with saturated sodium bicarbonate solution and extracted with DCM (100 ml). The organic layer was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (1.3 g, yield: 93%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.445 (d, J = 5.0 Hz, 1H), 7.52 (d, J = 9.0 Hz, 3H), 7.48 (s, 1H), 7.445-7.415 (m, 2H), 7.38- 7.34 (m, 1H), 7.07 (t, J = 9.0 Hz, 1H), 6.55 (dd, J = 13.0, 2.5 Hz, 1H), 6.47 (dd, J = 8.5, 2.0 Hz, 1H), 6.39 (d, J = 5.0 Hz, 1H), 5.49 (s, 2H), 5.30 (s, 2H), 3.95 (s, 3H); ES-MS: m / z 391.2 (M+H)+. Intermediate 17: Preparation of tert-butyl 4-((4-(4-amino-2-fluorophenoxy)-6- methoxyquinolin-7-yl)oxy)piperidine-1-carboxylate: Step 1: Synthesis of tert-butyl 4-hydroxypiperidine-1-carboxylate: To a stirred solution of piperidin-4-ol (10 g, 98.86 mmol, 1.0 eq) in DCM (100 ml) was added triethyl amine (16 ml, 118.63 mmol, 1.2 eq) and di-tertbutyl dicarbonate (25.8 g, 118.63 mmol, 1.2 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (200 ml) and washed with 1N HCl and water. The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (15 g, yield: 75.3%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 3.86-3.80 (m, 3H), 3.04-2.99 (m, 2H), 1.87-1.81 (m, 2H), 1.61 (m, 2H), 1.45 (s, 9H). Step 2: Synthesis of tert-butyl 4-((methylsulfonyl)oxy)piperidine-1-carboxylate: To a stirred solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (Step 1, 5 g, 24.838 mmol, 1.0 eq) in DCM (100 ml) was added triethylamine (3.7 g, 37.257 mmol, 1.5 eq), 4-dimethylaminopyridine (0.090 g, 0.745 mmol, 0.03 eq) and methane sulfonyl chloride (3.4 g, 29.806 mmol, 1.2 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (200 ml) and washed with water (200 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (6 g, yield: 86.9%) as a brown solid.1H NMR (500 MHz, CDCl3): δ ppm 4.90-4.86 (m, 1H), 3.72-3.68 (m, 2H), 3.32-3.27 (m, 2H), 3.04 (s, 3H), 1.99-1.93 (m, 2H), 1.84-1.78 (m, 2H), 1.46 (s, 9H); ES-MS: m / z 302.23 (M+Na)+. Step 3: Synthesis of tert-butyl 4-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7- yl)oxy)piperidine-1-carboxylate: To a stirred solution of 4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-ol (Intermediate 14-step 7, 4 g, 12.121 mmol, 1.0 eq) in Isopropanol (100 ml) was added potassium carbonate (5 g, 36.36 mmol, 3.0 eq) and tert-butyl 4- ((methylsulfonyl)oxy)piperidine-1-carboxylate (Step 2, 6.73 g, 24.24 mmol, 2.0 eq). The reaction mixture was stirred at 100 ºC for about 6 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The residue was diluted with DCM (100 ml) and washed with water. The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (2.7 g, yield: 43.5%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 8.56 (d, J = 5.5 Hz, 1H), 8.19 (dd, J = 10.0, 3.0 Hz, 1H), 8.16-8.13 (m, 1H), 7.53 (s, 1H), 7.46 (s, 1H), 7.357 (dd, J = 8.5, 7.5 Hz, 1H), 6.55 (d, J = 5.0 Hz, 1H), 4.74-4.69 (m, 1H), 4.0 (s, 3H), 3.87-3.84 (m, 2H), 3.32-3.27 (m, 2H), 2.11-2.07 (m, 2H), 1.92-1.85 (m, 2H), 1.47 (s, 9H); ES-MS: m / z 514.24 (M+H)+. Step 4: Synthesis of tert-butyl 4-((4-(4-amino-2-fluorophenoxy)-6-methoxyquinolin-7- yl)oxy)piperidine-1-carboxylate: To a stirred solution of tert-butyl 4-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin- 7-yl)oxy)piperidine-1-carboxylate (Step 3, 2.7 g, 5.257 mmol, 1.0 eq) in ethanol (180 ml) and water (45 ml) was added Iron powder (1.17 g, 21.029 mmol, 4.0 eq) and acetic acid (2.7 ml). The reaction mixture was stirred at 80 ºC for about 6 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with ethanol. The filtrate was evaporated under reduced pressure, residue was basified with saturated sodium bicarbonate solution and extracted with DCM (2x100 ml). The combined organic layer was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to obtain the title compound (2.3 g, yield: 90%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 8.46 (d, J = 5.0 Hz, 1H), 7.60 (s, 1H), 7.44 (s, 1H), 7.03 (t, J = 8.5 Hz, 1H), 6.56 (dd, J = 12.0, 2.5 Hz, 1H), 6.51-6.49 (m, 1H), 6.40 (dd, J = 5.5, 1.0 Hz, 1H), 4.70-4.65 (m, 1H), 4.02 (s, 3H), 3.87-3.85 (m, 2H), 3.81 (s, 2H), 3.29-3.24 (m, 2H), 2.10-2.07 (m, 2H), 1.91-1.84 (m, 2H), 1.47 (s, 9H); ES-MS: m / z 484.37 (M+H)+. Intermediate 18: Preparation of 4-((6-(benzyloxy)-7-methoxyquinolin-4-yl)oxy)-3- fluoroaniline: To a stirred solution of 4-chloro-7-methoxyquinolin-6-ol (Intermediate 15-Step 7, 1.0 g, 3.97 mmol, 1.0 eq) in DMF (10 ml) was added potassium carbonate (1.0 g, 7.947 mmol, 2.0 eq) and benzyl bromide (0.5 ml, 4.3709 mmol, 1.1 eq). The reaction mass stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass poured into water (150 ml), aqueous layer was extracted with ethyl acetate (3x150 ml). The combined organic layer was washed with water (300 ml) and brine solution (300 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient to obtain the title compound (0.800 g, yield: 67.2%) as a brown colour solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.62 (d, J = 4.5 Hz, 1H), 7.56-7.53 (m, 4H), 7.48 (s, 1H), 7.43 (t, J = 7.0 Hz, 2H), 7.38 (d, J = 7.5 Hz, 1H), 5.31 (s, 2H), 3.97 (s, 3H); ES-MS: m / z 300.22 (M+H)+. Step 2: Synthesis of 6-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline: Method 1: To a stirred solution of 6-(benzyloxy)-4-chloro-7-methoxyquinoline (Step 1, 0.800 g, 2.671 mmol, 1.0 eq) in diphenyl ether (16 ml) was added potassium carbonate (1.8 g, 13.355 mmol, 4.0 eq) and 2-fluoro-4-nitrophenol (0.629 g, 4.00 mmol, 1.5 eq). The reaction mixture was heated at 180 ºC (Internal temperature) for about 8 hours. TLC indicated starting material was consumed and the desired product was observed. Reaction mass cooled to room temperature, n-Hexane (200 mL) was added, stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum. The obtained solid was dissolved in DCM (200 ml), washed with water (100 ml). The aqueous layer was extracted with DCM (2x200 ml). The combined organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-4% methanol in dichloromethane gradient to obtain the title compound (0.650 g, yield: 57.9%) as a yellow colour solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.60 (d, J = 5.0 Hz, 1H), 8.46 (dd, J = 10.5, 3.0 Hz, 1H), 8.17-8.14 (m, 1H), 7.56 (s, 1H), 7.52 (t, J = 8.5 Hz, 1H), 7.48-7.47 (m, 3H), 7.40-7.31 (m, 3H), 6.83 (d, J = 5.0 Hz, 1H), 5.25 (s, 2H), 3.97 (s, 3H); ES-MS: m / z 421.40 (M+H)+. Method 2: To a stirred solution of 6-(benzyloxy)-4-chloro-7-methoxyquinoline (Step 1, 9.1 g, 30.35 mmol, 1.0 eq) in N-methyl-2-pyrrolidone (NMP) (45.5 ml) was added 2-fluoro-4- nitrophenol (7.6 g, 48.56 mmol, 1.6 eq) and N-ethyl-N-isopropylpropan-2-amine (13.7 g, 18.4 ml, 106.22 mmol, 3.5 eq). Reaction mass was stirred at around 160 °C for around 6 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, reaction mass was allowed to reach to room temperature. Reaction mass cooled to 0-10oC, water (455 ml) was added stirred at 0-10 °C for around 1 hour. Solid was filtered, washed with water (350 ml) and then dried under vacuum at 50 °C for about 4 hours. Methanol (45 ml) was added to the solid, stirred at room temperature for about 3 hours. Solid was filtered, washed with methanol (5 ml) and then dried under vacuum to afford the title compound (8.4 g, yield: 65.83%) as a pale-yellow colour solid. ES-MS: m / z 421.15 (M+H)+. Step 3: Synthesis of 4-((6-(benzyloxy)-7-methoxyquinolin-4-yl)oxy)-3-fluoroaniline: To a stirred solution of 6-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-7- methoxyquinoline (Step 2, 0.600 g, 1.427 mmol, 1.0 eq) in ethanol (14 ml) and water (2.8 ml) was added Iron powder (0.318 g, 5.708 mmol, 4.0 eq) and acetic acid (0.12 ml). The reaction mixture was stirred at 80 ºC for about 6 hours. TLC indicated starting material was consumed and the desired product was observed. Reaction mass filtered through celite bed, washed with ethanol and evaporated under reduced pressure. The crude compound was basified with saturated sodium bicarbonate solution, extracted with DCM (2x200 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and evaporated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to obtain the title compound (0.500 g, yield: 89.7%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.47 (d, J = 5.5 Hz, 1H), 7.66 (s, 1H), 7.53 (d, J = 7.5 Hz, 2H), 7.44-7.34 (m, 4H), 7.06 (t, J = 9.0 Hz, 1H), 6.55 (dd, J = 13.0, 2.0 Hz, 1H), 6.47 (dd, J = 8.5, 2.0 Hz, 1H), 6.40 (d, J = 5.0 Hz, 1H), 5.49 (s, 2H), 5.27 (s, 2H), 3.95 (s, 3H); ES-MS: m / z 391.32 (M+H)+. Intermediate 19: Preparation of 2-((tert-butoxycarbonyl)amino)ethyl methanesulfonate: Step 1: Synthesis of tert-butyl (2-hydroxyethyl)carbamate: To a solution of 2-aminoethan-1-ol (5.0 g, 81.85 mmol, 1.0 eq) in DCM (100 ml) at 0 ºC was added triethylamine (12.42 g, 17.1 ml, 122.73 mmol, 1.5 eq) and di-tert-butyl dicarbonate (17.86 g, 18.80 ml, 81.85 mmol, 1.0 eq). Cooling bath was removed and the reaction mass stirred at room temperature for overnight. Reaction mass quenched with saturated ammonium chloride solution (100 ml), stirred at room temperature for about 10 minutes. Organic layer was separated, and aqueous layer was extracted with DCM (3x100 ml). The combined organic layer was washed with water (100 ml) and brine solution (100 ml). The organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure to obtain the product (3.5 g) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 6.66 (s, 1H), 4.55 (t, J = 5.5 Hz, 1H), 3.35 (dd, J = 12.0, 6.0 Hz, 2H), 2.97 (dd, J = 12.5 Hz, 6.5 Hz, 2H), 1.37 (s, 9H); ES-MS: m / z 183.97 (M+Na)+. Step 2: Synthesis of 2-((tert-butoxycarbonyl)amino)ethyl methanesulfonate: To a solution of tert-butyl (2-hydroxyethyl)carbamate (Step 1, 1.0 g, 6.206 mmol, 1.0 eq) in DCM (10 ml) at 0-10 ºC was added trimethylamine (0.785 g, 1.08 ml, 7.757 mmol, 1.25 eq) and methanesulfonylchloride (0.85 g, 0.57 ml, 7.419 mmol, 1.2 eq). Cooling bath was removed and the reaction mass stirred at room temperature for overnight. Reaction mass quenched with saturated sodium bicarbonate solution (20 ml) and extracted with DCM (2x40 ml). The combined organic layer was washed with water (20 ml) and brine solution (20 ml). The organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure to obtain (1.3 g) the product as a semi-solid. The obtained compound was used for next step without further purification.1H NMR (500 MHz, DMSO-d6): δ ppm 7.06 (t, J = 5.5 Hz, 1H), 4.15 (t, J = 5.5 Hz, 2H), 3.25-3.21 (m, 2H), 3.16 (s, 3H), 1.38 (s, 9H); ES-MS: m / z 261.92 (M+Na)+. Intermediate 20: Preparation of (E)-4-((4-fluorophenyl)amino)-4-oxobut-2-enoic acid: Step 1: Synthesis of methyl (E)-4-((4-fluorophenyl)amino)-4-oxobut-2-enoate: A solution of (E)-4-methoxy-4-oxobut-2-enoic acid (3.0 g, 23.05 mmol, 1.0 eq), 4- Fluoroaniline (2.8 g, 25.36 mmol, 1.1 eq) and DMF (30 ml) cooled to 0 ºC. N-Ethyl diisopropyl amine (7.4 g, 10 ml, 57.62 mmol, 2.5 eq) and HATU (17.52 g, 46.1 mmol, 2.0 eq) were added, stirred at 0-10 ºC for about 1 hour. Cooling bath was removed and the reaction mass stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass cooled to 0-20 ºC, Water (450 ml) was added, stirred at 0-20 ºC for about 1 hour. Solid was filtered, washed with water (150 ml) and then dried under vacuum. The obtained solid was purified by column chromatography (silica gel, 60-120 mesh) using 0-5% methanol in dichloromethane gradient to obtain the product (4.87 g, yield: 94%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.61 (s, 1H), 7.71- 7.68 (m, 2H), 7.22-7.17 (m, 2H), 7.19 (d, J = 15.5 Hz, 1H), 6.73 (d, J = 15.5 Hz, 1H), 3.76 (s, 3H); ES-MS: m / z 223.83 (M+H)+. Step 2: Synthesis of (E)-4-((4-fluorophenyl)amino)-4-oxobut-2-enoic acid: To a solution of methyl (E)-4-((4-fluorophenyl)amino)-4-oxobut-2-enoate (Step 1, 4.5 g, 20.161 mmol, 1.0 eq) in methanol (22.5 ml) and THF (22.5 ml) was added 1N KOH solution (140.8 ml, 141.13 mmol, 7.0 eq). The reaction mass stirred at 10 to 20 ºC for around 5 hours. TLC indicated starting material was completed. Reaction mass cooled to 10 to 20 ºC, 1N HCl was added till reaction mass pH reaches to 8.0. Reaction mass evaporated under reduced pressure at bath temperature below 40 ºC. Reaction mass cooled to 10-20 ºC, pH adjusted to 3.0 with 1N HCl. The resulting solid was filtered, washed with water (40 ml) and then dried under vacuum to obtain the product (3.9 g) as a solid;1H NMR (500 MHz, DMSO-d6): δ ppm 13.0 (s, 1H), 10.56 (s, 1H), 7.71-7.68 (m, 2H), 7.19 (t, J = 9.0 Hz, 2H), 7.12 (d, J = 15.0 Hz, 1H), 6.66 (d, J = 15.5 Hz, 1H). Intermediate 21: Preparation of (Z)-4-((4- -4-oxobut-2-enoic acid: A solution of furan-2,5-dione (10.0 g, 101.97 mmol, 1.0 eq) and THF (50 ml) cooled to 0-10 ºC.4-Fluoroaniline (11.33 g, 9.8 ml, 101.97 mmol, 1.0 eq) mixed in THF (10 ml) was added dropwise over a period of 10 minutes. The reaction mass stirred at 0-10 ºC for about 1 hour. Cooling bath was removed and the reaction mass stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure until no more THF was distilled out. Water (100 ml) was added to the reaction mass, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum. Solid was further dried under vacuum at 50-60 ºC for about 2 hours to obtain the product (16.6 g, yield: 78%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 13.07 (brs, 1H), 10.42 (s, 1H), 7.64 (dd, J = 9.0, 5.0 Hz, 2H), 7.17 (t, J = 9.0 Hz, 2H), 6.46 (d, J = 12.0 Hz, 1H), 6.30 (d, J = 12.0 Hz, 1H); ES-MS: m / z 210.35 (M+H)+. Intermediate 22: Preparation of 4-((4-fluorophenyl)amino)-4-oxobutanoic acid: To a solution of succinic anhydride (3.0 g, 29.98 mmol, 1.0 eq) in THF (30 ml) was added 4-Fluoroaniline (3.33 g, 2.84 ml, 29.98 mmol, 1.0 eq). The reaction mass was refluxed for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure until no more THF was distilled out. Water (60 ml) was added to the reaction mass stirred at room temperature for about 30 minutes. Solid was filtered, washed with water (15 ml) and then dried under vacuum. The solid was further dried under vacuum at 50 ºC for about 1 hour to obtain the product (5 g, yield: 79%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.12 (brs, 1H), 10.0 (s, 1H), 7.60-7.57 (m, 2H), 7.12 (t, J = 9.0 Hz, 2H), 2.56-2.51 (m, 4H); ES-MS: m / z 212.21 (M+H)+. Intermediate 23: Preparation of racemic 2-((4-fluorophenyl)carbamoyl)cyclopropane-1- carboxylic acid: To a solution of 3-oxabicyclo[3.1.0]hexane-2,4-dione (10 g, 89.32 mmol, 1.0 eq) in THF (50 ml) was added 4-Fluoroaniline (9.914 g, 8.45 ml, 89.32 mmol, 1.0 eq) mixed in THF (10 ml) dropwise over a period of 20 minutes. The reaction mass stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure until no more THF was distilled out. Water (100 ml) was added to the reaction mass, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum. Solid was further dried under vacuum at 50-60 ºC for about 2 hours to obtain the product (15.53 g, yield: 78%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.14 (brs, 1H), 10.19 (s, 1H), 7.58 (dd, J = 9.0, 5.0 Hz, 2H), 7.12 (dd, J = 15.5, 2.0 Hz, 2H), 2.18-2.14 (m, 1H), 2.03-1.98 (m, 1H), 1.43-1.39 (m, 1H), 1.17-1.13 (m, 1H). To a solution of 3-oxabicyclo[3.2.0]heptane-2,4-dione (5 g, 39.647 mmol, 1.0 eq) in THF (15 ml) was added 4-Fluoroaniline (4.40 g, 3.79 ml, 39.647 mmol, 1.0 eq) mixed in THF (10 ml) dropwise over a period of 10 minutes. The reaction mass stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure until no more THF was distilled out. Water (50 ml) was added to the reaction mass, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum. Solid was further dried under vacuum at 50-60 ºC for about 2 hours to obtain the product (6.77 g, yield: 72%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 11.96 (s, 1H), 9.83 (s, 1H), 7.58 (dd, J = 14.0.5.0 Hz, 2H), 7.11 (t, J = 8.5 Hz, 2H), 3.44-3.35 (m, 2H), 2.37- 2.30 (m, 1H), 2.11-1.99 (m, 3H); ES-MS: m / z 238.24 (M+H)+. Intermediate 25: Preparation of racemic 2-((4-fluorophenyl)carbamoyl)cyclopentane-1- carboxylic acid: To a solution of tetrahydro-1H-cyclopenta[c]furan-1,3(3aH)-dione (10 g, 71.35 mmol, 1.0 eq) in THF (50 ml) was added 4-Fluoroaniline (7.92 g, 6.75 ml, 71.35 mmol, 1.0 eq) mixed in THF (10 ml) dropwise over a period of 10 minutes. The reaction mass stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure until no more THF was distilled out. Water (100 ml) was added to the reaction mass, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum. Solid was further dried under vacuum at 50-60 ºC for about 2 hours to obtain the product (13.63 g, yield: 76%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 11.87 (s, 1H), 9.88 (s, 1H), 7.57 (dd, J = 9.0, 5.0 Hz, 2H), 7.10 (t, J = 9.0 Hz, 2H), 3.13- 3.08 (m, 1H), 2.94 (q, J = 8.0 Hz, 1H), 2.03-1.90 (m, 2H), 1.87-1.76 (m, 3H), 1.58-1.55 (m, 1H); ES-MS: m / z 252.4 (M+H)+. Intermediate 26: Preparation of racemic 2-((4-fluorophenyl)carbamoyl)cyclohexane-1- carboxylic acid: To a solution of hexahydroisobenzofuran-1,3-dione (40 g, 259.44 mmol, 1.0 eq) in THF (100 ml) was added 4-Fluoroaniline (28.82 g, 24.56 ml, 259.36 mmol, 1.0 eq) mixed in THF (20 ml) dropwise over a period of 40 minutes. Exothermic. Internal temperature rises to 60 ºC. The reaction mass stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure until no more THF was distilled out. Water (400 ml) was added to the reaction mass, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (200 ml) and then dried under vacuum. Solid was further dried under vacuum at 50-60 ºC for about 2 hours to obtain the product (46.6 g, yield: 67.7%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 11.96 (s, 1H), 9.77 (s, 1H), 7.58 (dd, J = 9.0, 5.0 Hz, 2H), 7.10 (t, J = 9.0 Hz, 2H), 2.93-2.90 (m, 1H), 2.61-2.57 (m, 1H), 2.11-2.08 (m, 1H), 2.02- 1.96 (m, 1H), 1.77-1.62 (m, 3H), 1.42-1.38 (m, 2H), 1.32-1.29 (m, 1H); ES-MS: m / z 266.29 (M+H)+. Intermediate 27: Preparation of 2-methoxyethyl methanesulfonate: To a stirred solution of 2-methoxyethan-1-ol (1 g, 13.14 mmol, 1.0 eq) in DCM (10 ml) at 0-10 ºC was added triethylamine (5.5 ml, 39.42 mmol, 3.0 eq) followed by methane sulfonyl chloride (1.32 ml, 17.08 mmol, 1.3 eq). The reaction mass stirred at room temperature for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mass was diluted with DCM (150 ml) and washed with water (100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained compound was used for next step without further purification.1H NMR (500 MHz, DMSO-d6): δ ppm 4.37-4.36 (m, 2H), 3.67-3.65 (m, 2H), 3.41 (s, 3H), 3.06 (s, 3H). Intermediate 28: Preparation of 4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline: To a stirred solution of sodium tert-butoxide (4.2 g, 1.0 eq.) in N,N-dimethylacetamide (120 mL, 12 vol) was added 6, 7-dimethoxy-4-chloroquinoline (10 g, 1.0 eq) and 4-hydroxy aniline (7 g, 1.4 eq.) at room temperature and stirred for about 10 min. The resulting mixture was heated to reflux (104-107 ºC) and stirred for about 14 hours. After completion of reaction confirmed by TLC, cool the reaction mixture to 10-15 ºC. Add water (200 mL, 20 vol) at 10- 15 ºC and stir for about 24 hours. The obtained solid was filtered and washed with water (100 mL) and dried the solid. The dried solid was taken in THF (7 vol) and DMA (4 vol) stir at room temperature for about 2 hours. Filtered the solid and dried under vacuum to obtain the desired product (7 g, yield: 53%).1H NMR: DMSO; δ 8.46 (d, J = 5 Hz, 1H), 7.58 (s, 1H), 7.40 (s, 1H), 6.97-7.00 (m, 2H), 6.78-6.74 (m, 2H), 6.42 (d, J = 5 Hz, 1H), 4.48 (s, 6H), 3.71 (s, 2H, NH2); Mass: m / z 297 (M+H)+. Intermediate 29: Preparation of 3-((tert- methanesulfonate: To a solution of tert-butyl (3-hydroxypropyl)carbamate (2 g, 11.41 mmol, 1.0 eq) in DCM (40 ml) at 0-10 °C was added triethylamine (2.30 g, 3.17 ml, 22.72 mmol, 2.0 eq) and methane sulfonyl chloride (1.96 g, 1.32 ml, 17.11 mmol, 1.5 eq). Cooling bath was removed, reaction mass stirred at room temperature for about 2 hours. Reaction mass quenched with water (30 ml), organic layer was separated, aqueous layer was extracted with DCM (2x40 ml). The combined organic layer was washed with brine solution (40 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure to afford the title compound (2.6 g) as an oil. Intermediate 30: Preparation of 3-methoxypropyl methanesulfonate: To a solution of 3-methoxypropan-1-ol (2 g, 22.19 mmol, 1.0 eq) in DCM (20 ml) at 0-10 °C was added Triethylamine (9.28 ml, 66.57 mmol, 3.0 eq) and methane sulfonyl chloride (2.23 ml, 28.84 mmol, 1.3 eq). Cooling bath was removed, reaction mass stirred at room temperature for about 2 hours. Reaction mass was diluted with DCM (20 ml), quenched with water (50 ml). Organic layer was separated, and the aqueous layer was extracted with DCM (2x40 ml). The combined organic layer was washed with brine solution (40 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure to afford the title compound (2.5 g) as an oil.1H NMR (500 MHz, DMSO-d6): δ ppm 4.23 (t, J = 6.5 Hz, 2H), 3.40 (t, J = 6.0 Hz, 2H), 3.24 (s, 3H), 3.15 (s, 3H), 1.91-1.86 (m, 2H). Intermediate 31: Preparation of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate: To a solution of tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (10 g, 43.419 mmol, 1.00 eq) in dichloromethane (100 mL) at 0 °C was added dropwise a solution of thionyl chloride (10.33 g, 6.2 ml, 86.838 mmol, 2.00 eq) in dichloromethane (12 mL). The resulting solution was stirred at 25 °C for overnight. The resulting mixture was concentrated under reduced pressure. The resulting residue was diluted with water (120 ml) and extracted with ethyl acetate (2x100 ml). The combined organic layer was washed with aqueous sodium bicarbonate solution (2x80 mL) and brine solution (2x80 mL). Organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was applied onto a silica gel column and eluted with ethyl acetate / petroleum ether (1:5) to obtain the title compound (5.61 g, yield: 52%) as an off-white solid. ES-MS: m / z 271.07 (M+Na)+. Intermediate 32: Preparation of tert-butyl 4-(2-((4-(4-amino-2-fluorophenoxy)-7- methoxyquinolin-6-yl)oxy)ethyl)piperazine-1-carboxylate: Step 1: Synthesis of 4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6-ol: To a solution of 6-(benzyloxy)-4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinoline (Intermediate 18-step 2, 8.3 g, 19.74 mmol, 1.0 eq) in trifluoroacetic acid (41.5 ml) was added methanesulfonic acid (2.5 ml, 39.48 mmol, 2.0 eq). Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure. Residue was neutralized to pH 7.0 with aqueous 1N NaOH solution. The resulting solid was collected by filtration, washed with water (50 ml) and then dried under vacuum. Crude compound was purified by column chromatography using 0-10% methanol in dichloromethane gradient to afford the title compound (5.8 g, yield: 89%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.83 (s, 1H), 8.76 (t, J = 2.5 Hz, 1H), 8.53-8.51 (m, 1H), 8.26 (d, J = 9.0 Hz,1H), 7.76 (t, J = 8.5 Hz, 1H), 7.55 (dd, J = 9.5, 2.5 Hz, 2H), 7.06 (d, J = 6.0 Hz, 1H), 4.03 (s, 3H); ES- MS: m / z 331.07 (M+H)+. Step 2: Synthesis of tert-butyl 4-(2-((4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6- yl)oxy)ethyl)piperazine-1-carboxylate: To a stirred solution of 4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6-ol (Step 1, 3.0 g, 9.08 mmol, 1.0 eq) in acetonitrile (25 ml) was added cesium carbonate (8.878 g, 27.25 mmol, 3.0 eq) and potassium iodide (0.45 g, 2.72 mmol, 0.3 eq). Reaction mass was stirred at room temperature for about 20 minutes, tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate (Intermediate 31, 3.388 g, 13.62 mmol, 1.5 eq) mixed in acetonitrile (5 ml) was added and the reaction mass was stirred at 60-70 °C for around 6 hours. Heating bath was removed, and the reaction mass was allowed to reach to room temperature. Reaction mass was evaporated under reduced pressure. Water (60 ml) was added to the residue, extracted with DCM (2x60 ml). The combined organic layer was washed with water (40 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (2.1 g, yield: 42.61%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.58 (d, J = 5.5 Hz, 1H), 8.19 (dd, J = 10.0, 2.5 Hz, 1H), 8.14 (dd, J = 8.5, 1.0 Hz, 1H), 7.47 (d, J = 7.5 Hz, 2H), 7.33 (dd, J = 8.5, 8.0 Hz, 1H), 6.55 (d, J = 5.5 Hz, 1H), 4.3 (t, 2H), 4.03 (s, 3H), 3.45 (t, J = 5.0 Hz, 4H), 2.95 (t, 2H), 2.58-2.57 (m, 4H), 1.45 (s, 9H); ES-MS: m / z 543.27 (M+H)+. Step 3: Synthesis of tert-butyl 4-(2-((4-(4-amino-2-fluorophenoxy)-7-methoxyquinolin-6- yl)oxy)ethyl)piperazine-1-carboxylate To tert-butyl 4-(2-((4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6- yl)oxy)ethyl)piperazine-1-carboxylate (Step 2, 2 g, 3.686 mmol, 1.0 eq) in methanol (20 ml) and water (2 ml) was added iron powder (1.0 g, 18.431 mmol, 5.0 eq) and acetic acid (2 ml). Reaction mass was stirred at 50-60oC for around 4 hours. After completion of the reaction monitored by TLC, heating bath was removed, reaction mass was allowed to reach to room temperature. DCM (100 ml) was added to the reaction mass, stirred at room temperature for 30 minutes. Reaction mass was filtered through celite bed, washed with DCM (100 ml). Filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, aqueous layer was extracted with DCM (2x60 ml). The combined organic layer was washed with water (40 ml) and brine solution (40 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (1.5 g, yield: 79.36%) as a solid.1H NMR (500 MHz, CD3OD): δ ppm 8.40 (d, J = 5.0 Hz, 1H), 7.69 (d, J = 3.5 Hz, 1H), 7.35 (s, 1H), 7.03 (t, J = 9.0 Hz, 1H), 6.61 (dd, J = 13.0, 3.0 Hz, 1H), 6.57 (dd, J = 8.5, 2.0 Hz, 1H), 6.47 (d, J = 5.5 Hz, 1H), 4.34 (t, 2H), 4.01 (s, 3H), 3.46 (m, 4H), 2.94 (t, J = 5.0 Hz, 2H), 2.63 (t, J = 5.0 Hz, 4H), 1.45 (s, 9H); ES-MS: m / z 535.28 (M+Na)+. Intermediate 33: Preparation of tert-butyl 4-(3-chloropropyl)piperazine-1-carboxylate: Stir tert-butyl piperazine-1-carboxylate (15 g, 80.5 mmol, 1.0 eq), 5M aqueous NaOH (17 ml) and 1-bromo-3-chloropropane (12.67 g, 80.5 mmol, 1.0 eq) together in acetone (150 ml) under a nitrogen atmosphere at room temperature for about 3 hours. Solvent was evaporated under reduced pressure. Dilute the reaction mass with water (170 ml) and the aqueous layer was extracted with DCM (3x100 ml). Combined organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained compound (15 g) was used for next step without further purification. Intermediate 34: Preparation of tert-butyl 4-(3-((4-(4-amino-2-fluorophenoxy)-7- methoxyquinolin-6-yl)oxy)propyl)piperazine-1-carboxylate: Step 1: Synthesis of tert-butyl 4-(3-((4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)piperazine-1-carboxylate: To a stirred suspension of 4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin-6-ol (Intermediate 32-step 1, 3.0 g, 9.08 mmol, 1.0 eq) in acetonitrile (60 ml) was added cesium carbonate (8.87 g, 27.25 mmol, 3.0 eq) and potassium iodide (0.452 g, 2.72 mmol, 0.3 eq). Reaction mixture was stirred at room temperature for about 20 minutes. tert-butyl 4-(3- chloropropyl)piperazine-1-carboxylate (Intermediate 33, 3.58 g, 13.62 mmol, 1.5 eq) dissolved in acetonitrile (10 ml) was added and the reaction mass was stirred at 60-70 °C for around 6 hours. Reaction mass was evaporated under reduced pressure. Water (90 ml) was added to the residue, extracted with DCM (2x60 ml). The combined organic layer was washed with water (30 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to afford the title compound (3.1 g, yield: 61.38%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.57 (d, J = 5.5 Hz, 1H), 8.45 (dd, J = 10.5, 3.0 Hz, 1H), 8.20 (td, J = 9.0, 1.5 Hz, 1H), 7.60 (t, J = 8.5 Hz, 1H), 7.45 (d, J = 6.0 Hz, 2H), 6.78 (d, J = 5.0 Hz, 1H), 4.16 (t, J = 6.5 Hz, 2H), 3.96 (s, 3H), 3.27 (m, 4H), 2.45 (t, J = 7.0 Hz, 2H), 2.32-.2.30 (m, 4H), 1.97-1.91 (m, 2H), 1.38 (s, 9H); ES-MS: m / z 557.32 (M+H)+. Step 2: Synthesis of tert-butyl 4-(3-((4-(4-amino-2-fluorophenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)piperazine-1-carboxylate: To a suspension of tert-butyl 4-(3-((4-(2-fluoro-4-nitrophenoxy)-7-methoxyquinolin- 6-yl)oxy)propyl)piperazine-1-carboxylate (Step 1, 3.0 g, 5.39 mmol, 1.0 eq) in Methanol (60 ml) and water (12 ml) was added Iron powder (1.5 g, 26.94 mmol, 5.0 eq) and acetic acid (3 ml). Reaction mass was stirred at 50-60 °C for around 5 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, and the reaction mass was allowed to reach to room temperature. Ethyl acetate (160 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. Reaction mass was filtered through celite bed, washed with Ethyl acetate (100 ml). Filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, and the aqueous layer was extracted with Ethyl acetate (2x60 ml). The combined organic layer was washed with water (30 ml) and brine solution (30 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (2.23 g, yield: 78.57%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.45 (d, J = 5.0 Hz, 1H), 7.51 (d, J = 7.0 Hz, 1H), 7.38 (d, J = 5.5 Hz, 1H), 7.20-7.14 (m, 1H), 7.06 (t, J = 9.0 Hz, 1H), 6.56-6.44 (m, 1H), 6.38 (t, J = 4.0 Hz, 1H), 5.48 (s, 2H), 4.20-4.16 (m, 2H), 3.94 (s, 3H), 3.30 (m, 4H), 2.47-2.46 (m, 2H), 2.33 (m, 4H), 1.96 (t, J = 6.5 Hz, 2H), 1.38 (s, 9H); ES-MS: m / z 527.32 (M+H)+. Intermediate 35: Preparation of tert-butyl 4-(2-((4-(4-amino-2-fluorophenoxy)-6- methoxyquinolin-7-yl)oxy)ethyl)piperazine-1-carboxylate: Step 1: Synthesis of tert-butyl 4-(2-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7- yl)oxy)ethyl)piperazine-1-carboxylate: To a stirred solution of 4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-ol (Intermediate 14-step 7, 3.5 g, 10.597 mmol, 1.0 eq) in acetonitrile (25 ml) was added cesium carbonate (10.3 g, 31.791 mmol, 3.0 eq) and potassium iodide (0.52 g, 3.179 mmol, 0.3 eq). The reaction mixture was stirred at room temperature for about 20 minutes, tert-butyl 4-(2- chloroethyl)piperazine-1-carboxylate (Intermediate 31, 3.9 g, 15.896 mmol, 1.5 eq) mixed in acetonitrile (10 ml) was added and the reaction mixture was stirred at 60-70 °C for around 5 hours. Reaction mixture was evaporated under reduced pressure. Water (200 ml) was added to the residue, extracted with DCM (2x200 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (3.1 g, yield: 53.9%) as a solid.1H NMR (500 MHz, CD3OD): δ ppm 8.51 (d, J = 5.5 Hz, 1H), 8.32 (dd, J = 10.5, 2.5 Hz, 1H), 8.22 (dd, J = 9.0, 1.5 Hz, 1H), 7.58 (t, J = 7.5 Hz, 2H), 7.42 (s, 1H), 6.715 (d, J = 5.0 Hz, 1H), 4.36 (t, J = 5.0 Hz, 2H), 4.0 (s, 3H), 3.47 (m, 4H), 2.97 (t, J = 5.0 Hz, 2H), 2.64 (t, J = 5.0 Hz, 4H), 1.46 (s, 9H); ES-MS: m / z 543.27 (M+H)+. Step 2: Synthesis of tert-butyl 4-(2-((4-(4-amino-2-fluorophenoxy)-6-methoxyquinolin-7- yl)oxy)ethyl)piperazine-1-carboxylate: To a stirred suspension of tert-butyl 4-(2-((4-(2-fluoro-4-nitrophenoxy)-6- methoxyquinolin-7-yl)oxy)ethyl)piperazine-1-carboxylate (Step 1, 3.0 g, 5.53 mmol, 1.0 eq) in Methanol (30 ml) and water (3 ml) was added Iron powder (1.544 g, 27.64 mmol, 5.0 eq) and acetic acid (3 ml). Reaction mass was stirred at 50-60 °C for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. Ethyl acetate (150 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. Reaction mass was filtered through celite bed, washed with ethyl acetate (100 ml). Filtrate was basified to around pH 8.0 with saturated sodium bicarbonate solution. Organic and aqueous layers were separated. Aqueous layer was extracted with ethyl acetate (200 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained compound was treated with MTBE (5 ml) and Hexane (45 ml), stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum to afford the title compound (2.6 g) as a pale-yellow solid.1H NMR (500 MHz, CD3OD): δ ppm 8.40 (d, J = 5.5 Hz, 1H), 7.64 (s, 1H), 7.35 (s, 1H), 7.04 (t, J = 8.5 Hz, 1H), 6.62 (dd, J = 13.0, 2.5 Hz, 1H), 6.56 (dd, J = 9.5, 2.5 Hz, 1H), 6.48 (d, J = 5.5 Hz, 1H), 4.34 (t, J = 5.0 Hz, 2H), 4.01 (s, 3H), 3.47 (m, 4H), 2.96 (t, J = 5.0 Hz, 2H), 2.65 (t, J = 5.0 Hz, 4H), 1.46 (s, 9H). Intermediate 36: Preparation of tert-butyl 4-(3-((4-(4-amino-2-fluorophenoxy)-6- methoxyquinolin-7-yl)oxy)propyl)piperazine-1-carboxylate: Step 1: Synthesis of tert-butyl 4-(3-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)piperazine-1-carboxylate: To a stirred solution of 4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-ol (Intermediate 14-step 7, 3.0 g, 9.08 mmol, 1.0 eq) in acetonitrile (40 ml) was added cesium carbonate (8.8 g, 27.25 mmol, 3.0 eq) and potassium iodide (0.452 g, 2.72 mmol, 0.3 eq). The reaction mixture was stirred at room temperature for about 20 minutes, tert-butyl 4-(3- chloropropyl)piperazine-1-carboxylate (Intermediate 33, 3.5 g, 13.62 mmol, 1.5 eq) mixed in acetonitrile (20 ml) was added and the reaction mixture was stirred at 80 °C for around 5 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, and the reaction mass was allowed to reach to room temperature. Reaction mass was evaporated under reduced pressure. Water (200 ml) was added to the residue, extracted with ethyl acetate (2x200 ml). Combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient to afford the title compound (2.02 g, yield: 40%) as a pale-yellow colour solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.56 (d, J = 5.0 Hz, 1H), 8.46 (dd, J = 10.0, 2.5 Hz, 1H), 8.20 (dd, J = 9.0, 1.5 Hz, 1H), 7.61 (t, J = 8.5 Hz, 1H), 7.45 (s, 2H), 6.78 (d, J = 5.5 Hz, 1H), 4.21 (t, J = 6.0 Hz, 2H), 3.92 (s, 3H), 3.31 (m, 4H), 2.48-2.47 (m, 2H), 2.35 (m, 4H), 1.98 (t, J = 7.0 Hz, 2H), 1.39 (s, 9H); ES-MS: m / z 557.29 (M+H)+. Step 2: Synthesis of tert-butyl 4-(3-((4-(4-amino-2-fluorophenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)piperazine-1-carboxylate: To a suspension of tert-butyl 4-(3-((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin- 7-yl)oxy)propyl)piperazine-1-carboxylate (Step 1, 2.0 g, 3.59 mmol, 1.0 eq) in Methanol (40 ml) and water (8 ml) was added Iron powder (1.0 g, 17.96 mmol, 5.0 eq) and acetic acid (2 ml). Reaction mass was stirred at 60 °C for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, and the reaction mass was allowed to reach to room temperature. Ethyl acetate (100 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. Reaction mass was filtered through celite bed, washed with Ethyl acetate. Filtrate was basified to around pH 8.0 with saturated sodium bicarbonate solution. Organic layer was separated, and the aqueous layer was extracted with Ethyl acetate (2x100 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained crude compound was treated with Methyl-tert-butyl ether (5 ml) and hexane (45 ml), stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum to afford the title compound (1.4 g, yield: 74%) as a yellow colour solid.1H NMR (500 MHz, CDCl3): δ ppm 8.40 (brs, 1H), 7.64 (s, 1H), 7.34 (s, 1H), 7.04 (t, J = 9.0 Hz, 1H), 6.62 (dd, J = 12.5, 2.5 Hz, 1H), 6.57 (dd, J = 8.5, 2.5 Hz, 1H), 6.48 (d, J = 5.5 Hz, 1H), 4.26 (t, J = 6.0 Hz, 2H), 4.03 (s, 3H), 3.50 (m, 4H), 2.77 (t, J = 7.5 Hz, 2H), 2.62 (m, 4H), 2.17 (dd, J = 13.0, 6.0 Hz, 2H), 1.46 (s, 9H); ES-MS: m / z 527.30 (M+H)+. Intermediate 37: Preparation of 3-((tert-butyldimethylsilyl)oxy)propyl methanesulfonate: Step 1: Synthesis of 3-((tert-butyldimethylsilyl)oxy)propan-1-ol: propane-1,3-diol (5 g, 65.71 mmol, 1.0 eq) was dissolved in DCM (200 mL) and triethylamine (6.65 g, 9.17 mL, 65.71 mmol, 1.0 eq). A solution of t-butyldimethylsilyl chloride (9.90 g, 65.68 mmol, 1.0 eq) in CH2Cl2 (25 mL) was added slowly over a period of 1 hour. After stirring for about 16 hours at room temperature, the reaction mass was washed with 10% aqueous NaHCO3 (60 mL) solution, water (60 mL), and brine solution (60 mL). Organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. Crude compound was purified by column chromatography (silica gel, 10-30% EtOAc in hexane) to afford the title compound (9 g, yield: 72%) as a colourless liquid.1H NMR (500 MHz, DMSO-d6): δ ppm 4.29 (t, J = 5.0 Hz, 1H), 3.63-3.60 (m, 2H), 3.42 (dd, J = 11.5, 6.5 Hz, 2H), 1.60-1.54 (m, 2H), 0.83 (s, 9H), 0.02 (s, 6H). Step 2: Synthesis of 3-((tert-butyldimethylsilyl)oxy)propyl methanesulfonate: A solution of 3-((tert-butyldimethylsilyl)oxy)propan-1-ol (Step 1, 2 g, 10.5 mmol, 1.0 eq) in DCM (20 ml) cooled to 0-10 °C. Triethylamine (2.93 ml, 21.0 mmol, 2.0 eq) and methane sulfonyl chloride (1.805 g, 1.22 ml, 15.76 mmol, 1.5 eq) were added, reaction mass was stirred at 0-10 °C for about 1 hour and stirred at room temperature for about 2 hours. Reaction mass was quenched with brine solution (30 ml) and extracted with DCM (2x40 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by silica gel column chromatography using 0-30% ethyl acetate in hexanes gradient to afford the title compound (1.2 g, yield: 42.55%) as a colourless oil. Intermediate 38: Preparation of 2-((tert-butyldimethylsilyl)oxy)ethyl methanesulfonate: Step 1: Synthesis of 2-((tert-butyldimethylsilyl)oxy)ethan-1-ol: 1,2-Ethanediol (2 g, 32.22 mmol, 1.0 eq) was dissolved in DCM (20 mL) and triethylamine (3.91 g, 5.39 mL, 38.64 mmol, 1.2 eq). The mixture was cooled to 0-10 °C, then a solution of t-butyldimethylsilyl chloride (4.853 g, 32.2 mmol, 1.0 eq) dissolved in CH2Cl2(10 mL) was added dropwise slowly over a period of about 1 hour. The mixture was stirred at room temperature for overnight. Reaction mixture was quenched with saturated aqueous ammonium chloride solution (20 ml) and layers were separated. Aqueous phase was extracted with DCM (2x60 ml). The combined organic layer was washed with water (30 ml), dried over Na2SO4, filtered, and concentrated under reduced pressure. Crude compound was purified by column chromatography (silica gel, 10-30 % EtOAc in hexane) to afford the title compound (3.97 g, yield: 70%) as a colourless liquid.1H NMR (500 MHz, DMSO-d6): δ ppm 4.54 (t, J = 5.5 Hz, 1H), 3.61 (t, J = 5.5 Hz, 2H), 3.45 (dd, J = 11.5, 5.5 Hz, 2H), 0.90 (s, 9H), 0.07 (s, 6H). Step 2: Synthesis of 2-((tert-butyldimethylsilyl)oxy)ethyl methanesulfonate: To a solution of 2-((tert-butyldimethylsilyl)oxy)ethan-1-ol (Step 1, 2 g, 11.34 mmol, 1.0 eq) in DCM (20 ml) at 0-10 °C was added Triethylamine (2.3 ml, 17.01 mmol, 1.5 eq) and methane sulfonyl chloride (0.96 ml, 12.47 mmol, 1.1 eq). Reaction mass was stirred at room temperature for about 4 hours. Reaction mass was diluted with DCM (100 ml), washed with saturated sodium bicarbonate solution (100 ml) and brine solution (100 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to afford the title compound (1 g, yield: 34.7%) as a colourless liquid.1H NMR (500 MHz, CDCl3): δ ppm 4.27 (t, J = 5.0 Hz, 2H), 3.86 (t, J = 5.0 Hz, 2H), 3.02 (s, 3H), 0.89 (s, 9H), 0.07 (s, 6H). Intermediate 39: Preparation of (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate: To a solution of (R)-tetrahydrofuran-3-ol (3.0 g, 34.048 mmol, 1.0 eq) and triethyl amine (6.89 g, 9.5 ml, 68.09 mmol, 2.0 eq) in DCM (39 ml) at 0-10 °C was added 4- methylbenzene-1-sulfonyl chloride (7.14 g, 37.45 mmol, 1.1 eq). Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mixture was diluted with DCM (60 ml) and washed with water (30 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, 15% ethyl acetate in hexane) to afford the title compound (4.27 g, yield: 51.75%) as a liquid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.81 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 5.12-5.10 (m, 1H), 3.76-3.64 (m, 4H), 2.43 (s, 3H), 2.11-2.04 (m, 1H), 1.91-1.89 (m, 1H); ES-MS: m / z 265.04 (M+Na)+. Intermediate 40: Preparation of tert-butyl 4-(((4-(4-amino-2-fluorophenoxy)-6- methoxyquinolin-7-yl)oxy)methyl)piperidine-1-carboxylate: Step 1: Synthesis of tert-butyl 4-(((methylsulfonyl)oxy)methyl)piperidine-1-carboxylate: To a solution of tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (5.0 g, 23.22 mmol, 1.0 eq) in DCM (50 ml) at 0-10 °C was added Triethylamine (4.7 g, 6.47 ml, 46.44 mmol, 2.0 eq) and methane sulfonyl chloride (2.68 ml, 4.0 g, 34.92 mmol, 1.5 eq). Cooling bath was removed, reaction mass was warmed to room temperature, stirred for about 2 hours. Reaction mass was diluted with DCM (100 ml), washed with 2% citric acid solution (40 ml) and water (40 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure to afford the title compound (6.3 g) as a liquid. Step 2: Synthesis of tert-butyl 4-(((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7- yl)oxy)methyl)piperidine-1-carboxylate: To a suspension of 4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7-ol (Intermediate 14-step 7, 2.3 g, 6.96 mmol, 1.0 eq) in acetonitrile (46 ml) was added potassium carbonate (1.924 g, 13.92 mmol, 2.0 eq). Reaction mass was stirred at room temperature for about 10 minutes. tert-butyl 4-(((methylsulfonyl)oxy)methyl)piperidine-1-carboxylate (step 1, 6.129 g, 20.88 mmol, 3.0 eq) and tetra-n-butyl ammonium iodide (0.771 g, 2.088 mmol, 0.3 eq) were added, stirred at 70-80 °C for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure, water (50 ml) was added to the residue, extracted with DCM (2x50 ml). The combined organic layer was washed with brine solution (30 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (1.6 g, yield: 43.56%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.56 (d, J = 5.0 Hz, 1H), 8.46 (dd, J = 10.5, 2.5 Hz, 1H), 8.20 (dd, J = 9.5, 1.5 Hz, 1H), 7.61 (t, J = 8.5 Hz, 1H), 7.45 (s, 2H), 6.78 (d, J = 5.0 Hz, 1H), 4.05-3.97 (m, 4H), 3.92 (s, 3H), 2.78 (m, 2H), 2.02 (m, 1H), 1.80 (d, J = 12.0 Hz, 2H), 1.41 (s, 9H), 1.28-1.21 (m, 2H); ES-MS: m / z 550.24 (M+Na)+. Step 3: Synthesis of tert-butyl 4-(((4-(4-amino-2-fluorophenoxy)-6-methoxyquinolin-7- yl)oxy)methyl)piperidine-1-carboxylate: To a suspension of tert-butyl 4-(((4-(2-fluoro-4-nitrophenoxy)-6-methoxyquinolin-7- yl)oxy)methyl)piperidine-1-carboxylate (Step 2, 1.5 g, 2.843 mmol, 1.0 eq) in Methanol (30 ml) and water (6 ml) was added Iron powder (0.79 g, 14.21 mmol, 5.0 eq) and acetic acid (3 ml). Reaction mass was stirred at 55-60 °C for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, reaction mass was allowed to reach to room temperature. DCM (100 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. Reaction mass was filtered through celite bed, washed with DCM (100 ml). Filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, aqueous layer was extracted with DCM (2x50 ml). The combined organic layer was washed with water (30 ml) and brine solution (30 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0- 7% methanol in dichloromethane gradient to afford the title compound (0.850 g, yield: 60.11%) as a pale-yellow colour solid. ES-MS: m / z 498.27 (M+H)+. Intermediate 41: Preparation of racemic 3-((2,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (5 g, 35.67 mmol, 1.0 eq) in THF (25 ml) was added 2,4-difluoroaniline (4.606 g, 35.67 mmol, 1.0 eq) dissolved in THF (25 ml) dropwise over a period of 15 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (100 ml) was added to the residue, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum to afford the title compound (7 g, yield: 72.87%) as a white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.18 (s, 1H), 9.92 (s, 1H), 7.80-7.75 (m, 1H), 7.31-7.26 (m, 1H), 7.05-7.02 (m, 1H), 2.10 (d, J = 9.0 Hz, 1H), 1.89 (d, J = 9.5 Hz, 1H), 1.31 (s, 3H), 1.19 (s, 3H); ES-MS: m / z 292.07 (M+Na)+. Intermediate 42: Preparation of 6-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-3-amine: Step 1: Synthesis of 6,7-dimethoxy-4-((5-nitropyridin-2-yl)oxy)quinoline: To a suspension of 6,7-dimethoxyquinolin-4-ol (5.0 g, 24.36 mmol, 1.0 eq) in acetonitrile (150 ml) was added cesium carbonate (15.878 g, 48.72 mmol, 2.0 eq) and 2- chloro-5-nitropyridine (5.793 g, 36.54 mmol, 1.5 eq). Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was not completed, reaction mass was stirred at 60-70 °C for around 3 hours. TLC indicated starting material was completed and the desired product was observed. Reaction mass was evaporated under reduced pressure. Water (100 ml) was added to the residue, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (10 ml) and then dried under vacuum. Crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (4.6 g, yield: 57.68%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 9.49 (s, 1H), 8.87 (dd, J = 8.5, 7.5 Hz, 1H), 8.09 (dd, J = 24.0, 8.0 Hz, 2H), 7.58 (s, 1H), 6.92 (s, 1H), 6.21 (d, J = 8.0 Hz, 1H), 3.879 (s, 3H), 3.725 (s, 3H); ES-MS: m / z 350.09 (M+Na)+. Step 2: Synthesis of 6-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-3-amine: To a suspension of 6,7-dimethoxy-4-((5-nitropyridin-2-yl)oxy)quinoline (Step 1, 4.5 g, 13.748 mmol, 1.0 eq) in methanol (22.5 ml) and water (4.5 ml) was added Iron powder (3.84 g, 68.74 mmol, 5.0 eq) and acetic acid (4.5 ml). Reaction mass was stirred at 50-60 °C for around 4 hours. TLC indicated starting material was completed and the desired product was observed. Heating bath was removed, and the reaction mass was allowed to reach to room temperature. Ethyl acetate (100 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. Reaction mass was filtered through celite bed, washed with ethyl acetate (100 ml). Filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2x50 ml). The combined organic layer was washed with water (100 ml) and brine solution (50 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography (silica gel, 60- 120) using 0-8% methanol in dichloromethane gradient to afford the title compound (2.4 g, yield: 58.72%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.944 (d, J = 2.5 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.30 (d, J = 8.5 Hz, 1H), 7.173 (d, J = 3.0 Hz, 1H), 6.50 (s, 1H), 6.06 (d, J = 8.0 Hz, 1H), 5.80 (s, 2H), 3.85 (s, 3H), 3.65 (s, 3H); ES- MS: m / z 320.12 (M+Na)+. Intermediate 43: Preparation of 6-((6,7-dimethoxyquinolin-4-yl)oxy)-5-fluoropyridin-3- amine: Step 1: Synthesis of 4-((3-fluoro-5-nitropyridin-2-yl)oxy)-6,7-dimethoxyquinoline: To a suspension of 6,7-dimethoxyquinolin-4-ol (10 g, 48.73 mmol, 1.0 eq) in acetonitrile (200 ml) was added cesium carbonate (31.75 g, 97.46 mmol, 2.0 eq) and 2-chloro- 3-fluoro-5-nitropyridine (10.32 g, 58.47 mmol, 1.2 eq). Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. Reaction mass was evaporated under reduced pressure. Water (120 ml) was added to the residue, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum. Crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (2.18 g, yield: 13%) as a pale-yellow solid.1H NMR (500 MHz, DMSO- d6): δ ppm 9.41 (d, J = 2.5 Hz, 1H), 9.13 (dd, J = 9.0, 2.0 Hz, 1H), 8.01 (dd, J = 8.0, 1.0 Hz, 1H), 7.58 (s, 1H), 6.61 (d, J = 2.0 Hz, 1H), 6.23 (d, J = 7.5 Hz, 1H), 3.87 (s, 3H), 3.70 (s, 3H); ES-MS: m / z 368.09 (M+Na)+. Step 2: Synthesis of 6-((6,7-dimethoxyquinolin-4-yl)oxy)-5-fluoropyridin-3-amine: To a suspension of 4-((3-fluoro-5-nitropyridin-2-yl)oxy)-6,7-dimethoxyquinoline (Step 1, 2.0 g, 5.792 mmol, 1.0 eq) in methanol (20 ml) and water (4 ml) was added Iron powder (1.617 g, 28.95 mmol, 5.0 eq) and acetic acid (2.4 ml). Reaction mass was stirred at 50-60 °C for around 4 hours. TLC indicated starting material was completed and the desired product was observed. Heating bath was removed, and the reaction mass was allowed to reach to room temperature. Ethyl acetate (50 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. Reaction mass was filtered through celite bed, washed with ethyl acetate (75 ml). Filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2x50 ml). The combined organic layer was washed with water (50 ml) and brine solution (50 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography (silica gel, 60-120) using 0-3.5% methanol in dichloromethane gradient to afford the title compound (1.1 g, yield: 60.24%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.84 (d, J = 7.5 Hz, 1H), 7.81 (d, J = 2.0 Hz, 1H), 7.56 (s, 1H), 7.03 (dd, J = 12.0, 2.5 Hz, 1H), 6.31 (s, 1H), 6.21 (s, 2H), 6.09 (d, J = 7.5 Hz, 1H), 3.85 (s, 3H), 3.66 (s, 3H); ES-MS: m / z 338.12 (M+Na)+. Intermediate 44: Preparation of 4-((6,7- 4-yl)thio)aniline: Step 1: Synthesis of 6,7-dimethoxy-4-((4-nitrophenyl)thio)quinoline: To a stirred suspension of 4-Chloro-6,7-dimethoxyquinoline (10 g, 44.71 mmol, 1.0 eq) in N-methyl-2-pyrrolidone (NMP) (50 ml) was added 4-nitrobenzenethiol (10.4 g, 67.06 mmol, 1.5 eq). N-ethyl-N-isopropylpropan-2-amine (17.336 g, 23.36 ml, 134.12 mmol, 3.0 eq) was added dropwise slowly over a period of 15 minutes. Due to Exothermic nature, internal temperature rises to 40 to 50 °C. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was cooled to 0-10 °C, water (500 ml) was added, stirred at same temperature for about 30 minutes. Solid was filtered, washed with water (100 ml) and then dried under vacuum. The resulting compound was purified by column chromatography using 0-2% methanol in dichloromethane gradient to afford the title compound (10.4 g, yield: 67.9%) as a brown colour solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.68 (d, J = 4.5 Hz, 1H), 8.24 (dd, J = 9.0, 2.5 Hz, 1H), 8.19 (d, J = 8.5 Hz, 2H), 7.51 (dd, J = 9.5, 2.5 Hz, 2H), 7.43 (d, J = 4.5 Hz, 1H), 7.32 (s, 1H), 3.96 (s, 3H), 3.79 (s, 3H); ES-MS: m / z 343.09 (M+H)+. Step 2: Synthesis of 4-((6,7-dimethoxyquinolin-4-yl)thio)aniline: To a suspension of 6,7-dimethoxy-4-((4-nitrophenyl)thio)quinoline (Step 1, 10 g, 29.20 mmol, 1.0 eq) in Methanol (50 ml) and water (10 ml) was added Iron powder (8.156 g, 146.04 mmol, 5.0 eq) and acetic acid (10 ml). Reaction mass was stirred at 60-65 °C for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, reaction mass was allowed to reach to room temperature. DCM (200 ml) was added to the reaction mass, stirred at room temperature for about 30 minutes. Reaction mass was filtered through celite bed, washed with DCM (100 ml). Filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, aqueous layer was extracted with DCM (2x50 ml). The combined organic layer was washed with water (100 ml) and brine solution (50 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0-3.5% methanol in dichloromethane gradient to afford the title compound (3.2 g, yield: 35.07%) as a pale-yellow colour solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.38 (d, J = 5.0 Hz, 1H), 7.36 (s, 1H), 7.29 (s, 1H), 7.27 (t, J = 2.5 Hz, 1H), 7.25 (t, J = 2.5 Hz, 1H), 6.72 (t, J = 2.0 Hz, 1H), 6.70 (t, J = 2.0 Hz, 1H), 6.54 (d, J = 5.0 Hz, 1H), 3.94 (s, 3H), 3.93 (s, 3H); ES-MS: m / z 313.14 (M+H)+. Intermediate 45: Preparation of racemic 3-((4-fluorophenyl)(methyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (5 g, 35.67 mmol, 1.0 eq) in THF (30 ml) was added 4-fluoro-N-methylaniline (4.46 g, 4.3 ml, 35.67 mmol, 1.0 eq) mixed in THF (20 ml) dropwise over a period of 10 minutes. The reaction mass was stirred at 50-60 °C for around 3 hours. After completion of the reaction monitored by TLC, Reaction mass was evaporated under reduced pressure. Water (100 ml) was added to the reaction mass, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum. Solid was further dried under vacuum at 50-60 ºC for about 2 hours to afford the title compound (8.23 g, yield: 87%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.43 (s, 1H), 7.35-7.29 (m, 4H), 3.16 (s, 3H), 1.59 (d, J = 8.5 Hz, 1H), 1.54 (d, J = 8.5 Hz, 1H), 1.24 (s, 6H); ES-MS: m / z 288.04 (M+Na)+. Intermediate 46: Preparation of racemic 2,2-dimethyl-3-((2-methylbenzo[d]thiazol-6- yl)carbamoyl)cyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (5 g, 35.67 mmol, 1.0 eq) in THF (25 ml) was added 2-methylbenzo[d]thiazol-6-amine (5.85 g, 35.67 mmol, 1.0 eq) dissolved in THF (25 ml) dropwise over a period of 15 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (100 ml) was added to the residue, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum to afford the title compound (7.5 g, yield: 69.06%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.15 (s, 1H), 10.31 (s, 1H), 8.40 (d, J = 2.0 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.53-7.45 (m, 1H), 2.75 (s, 3H), 2.04 (d, J = 9.0 Hz, 1H), 1.91 (d, J = 9.0 Hz, 1H), 1.35 (s, 3H), 1.21 (s, 3H); ES-MS: m / z 305.13 (M+H)+. Intermediate 47: Preparation of racemic 3-((4-fluorobenzyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (10 g, 71.35 mmol, 1.0 eq) in THF (50 ml) was added (4-fluorophenyl)methanamine (8.933 g, 71.35 mmol, 1.0 eq) dissolved in THF (50 ml) dropwise over a period of 10 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was not consumed completely. Reaction mass was stirred at 50-60 °C for around 4 hours. Heating bath was removed, and the reaction mass was allowed to reach to room temperature. THF was evaporated under reduced pressure. Water (200 ml) was added to the residue, stirred at room temperature for about 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum to afford the title compound (16 g, yield: 84.52%) as a white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 13.10 (s, 1H), 8.93 (t, J = 5.5 Hz, 1H), 7.31 (dd, J = 9.0, 6.0 Hz, 2H), 7.16-7.13 (m, 2H), 4.29 (d, J = 6.0 Hz, 2H), 1.89 (d, J = 8.5 Hz, 1H), 1.86 (d, J = 9.0 Hz, 1H), 1.25 (s, 3H), 1.18 (s, 3H); ES-MS: m / z 288.10 (M+Na)+. Intermediate 48: Preparation of racemic 3-((3-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (5 g, 35.67 mmol, 1.0 eq) in THF (25 ml) was added 3-fluoroaniline (3.965 g, 35.67 mmol, 1.0 eq) mixed in THF (25 ml) dropwise over a period of 15 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (100 ml) was added to the solid, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum to obtain the title compound (7.5 g, yield: 83.66%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.08 (s, 1H), 10.26 (s, 1H), 7.56 (d, J = 14.0 Hz, 1H), 7.30 (dd, J = 15.0, 8.0 Hz, 1H), 7.25 (d, J = 8.5 Hz, 1H), 6.83 (td, J = 8.5, 2.5 Hz, 1H), 1.99 (d, J = 9.5 Hz, 1H), 1.89 (d, J = 9.0 Hz, 1H), 1.32 (s, 3H), 1.19 (s, 3H); ES-MS: m / z 250.05 (M-H)-. Intermediate 49: Preparation of racemic 3-((4- -2,2- dimethylcyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (5 g, 35.67 mmol, 1.0 eq) in THF (25 ml) was added 4-methoxyaniline (4.394 g, 35.67 mmol, 1.0 eq) dissolved in THF (25 ml) dropwise over a period of 15 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (100 ml) was added to the residue, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum to obtain the title compound (7.83 g, yield; 83.36%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.34 (s, 1H), 10.03 (s, 1H), 7.46 (d, J = 9.0 Hz, 2H), 6.85 (d, J = 9.0 Hz, 2H), 3.71 (s, 3H), 1.97 (d, J = 9.0 Hz, 1H), 1.87 (d, J = 9.0 Hz, 1H), 1.31 (s, 3H), 1.20 (s, 3H); ES-MS: m / z 262.08 (M-H)-. Intermediate 50: Preparation of 4-((2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-9-yl)oxy)-3- fluoroaniline: Step 1: Synthesis of 4-chloroquinoline-6,7-diol: A solution of 4-Chloro-6,7-dimethoxyquinoline (30 g, 134.13 mmol, 1.0 eq) in DCM (300 ml), was cooled to -20oC. Boron tribromide (335.33 ml, 335.33 mmol, 2.5 eq, 1.0M in DCM) was added dropwise slowly, reaction mass was stirred at same temperature for 2 hours. The reaction mixture was then allowed to reach room temperature and stirred for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mass was cooled to 0-10oC, quenched with water (300 ml) dropwise slowly, pH was adjusted to around 6.0 with 10% NaOH solution. DCM was evaporated under reduced pressure and then reaction mass was stirred at room temperature for around 1 hour. Solid was filtered, washed with water (100 ml) and then dried under vacuum. Acetonitrile (100 ml) was added to the resulting solid, stirred at room temperature for 30 minutes. Solid was filtered and then dried under vacuum to obtain the title compound (25 g) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.37 (brs, 2H), 8.50 (d, J = 5.0 Hz, 1H), 7.45 (d, J = 5.0 Hz, 1H), 7.37 (s, 1H), 7.31 (s, 1H); ES-MS: m / z 196.04 (M+H)+. Step 2: Synthesis of 9-chloro-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline: To a stirred solution of 4-chloroquinoline-6,7-diol (step 1, 4.0 g, 20.449 mmol, 1.0 eq) in DMF (40 ml) was added potassium carbonate (15.54 g, 112.47 mmol, 5.5 eq) and 1,2- dibromoethane (28.8 g, 17.35 ml, 153.37 mmol, 7.5 eq). The reaction mixture was stirred at 60oC for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, and the reaction mixture was cooled to room temperature. Water (600 ml) and ethyl acetate (300 ml) were added to the reaction mixture, organic layer was separated, and the aqueous layer was extracted with ethyl acetate (300 ml). The combined organic layer was washed with water (500 ml) and brine solution (300 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (2.5 g, 55.16% yield) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.61 (d, J = 4.5 Hz, 1H), 7.55 (d, J = 4.5 Hz, 1H), 7.49 (d, J = 6.5 Hz, 2H), 4.42 (s, 4H); ES-MS: m / z 222.04 (M+H)+. Step 3: Synthesis of 9-(2-fluoro-4-nitrophenoxy)-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline: To a stirred solution of 9-chloro-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline (step 2, 2.5 g, 11.312 mmol, 1.0 eq) in N-methyl-2-pyrrolidone (NMP) (25 ml) was added N-ethyl-N- isopropylpropan-2-amine (5.11 g, 6.8 ml, 39.59 mmol, 3.5 eq) and 2-fluoro-4-nitrophenol (2.8 g, 18.099 mmol, 1.6 eq). The reaction mixture was stirred at 150oC for around 6 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mass was allowed to cool to room temperature. Water (500 ml) was added to the reaction mass, stirred at room temperature for 20 minutes and then extracted with ethyl acetate (2x300 ml). The combined organic layer was washed with water (300 ml) and brine solution (300 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (3 g, 77.48% yield) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.58 (d, J = 5.0 Hz, 1H), 8.45 (dd, J = 10.5, 2.5 Hz, 1H), 8.19-8.17 (m, 1H), 7.57 (t, J = 8.5 Hz, 1H), 7.51 (s, 1H), 7.47 (s, 1H), 6.78 (d, J = 5.0 Hz, 1H), 4.41 (dd, J = 8.0, 5.0 Hz, 4H); ES-MS: m / z 343.1 (M+H)+. Step 4: Synthesis of 4-((2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-9-yl)oxy)-3-fluoroaniline: To a stirred solution of 9-(2-fluoro-4-nitrophenoxy)-2,3-dihydro-[1,4]dioxino[2,3- g]quinoline (step 3, 3 g, 8.764 mmol, 1.0 eq) in Methanol (15 ml) and water (3 ml) was added Iron powder (2.44 g, 43.82 mmol, 5.0 eq) and acetic acid (4.5 ml). The reaction mixture was stirred at 60oC for around 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was allowed to cool to room temperature. Ethyl acetate (150 ml) was added to the reaction mass, stirred at room temperature for 20 minutes. Reaction mass was filtered through celite bed, washed with ethyl acetate (70 ml). The filtrate was washed with 10% sodium carbonate solution (100 ml) and water (100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained crude compound was purified by column chromatography using 0-3% methanol in dichloromethane gradient to afford the title compound (2.0 g, yield: 73.07%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.45 (d, J = 5.0 Hz, 1H), 7.58 (s, 1H), 7.38 (s, 1H), 7.05 (t, J = 9.0 Hz, 1H), 6.54 (dd, J = 13.5, 2.5 Hz, 1H), 6.45 (dd, J = 9.0, 2.0 Hz, 1H), 6.35 (d, J = 5.5 Hz, 1H), 5.48 (s, 2H), 4.40 (s, 4H); ES-MS: m / z 335.05 (M+Na)+. Intermediate 51: Preparation of 5-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-2-amine: Step 1: Synthesis of 6,7-dimethoxy-4-((6-nitropyridin-3-yl)oxy)quinoline: To a solution of 6,7-dimethoxyquinolin-4-ol (11 g, 53.60 mmol, 1.0 eq) in DMF (88 ml) was added potassium carbonate (14.81 g, 107.20 mmol, 2.0 eq ) and 5-chloro-2- nitropyridine (8.498 g, 53.60 mmol, 1.0 eq). The reaction mass was stirred at 70-80oC for around 7 hours. TLC indicated starting material was consumed and the desired product was observed. Heating bath was removed, and the reaction mass was allowed to cool to room temperature. Reaction mass was cooled to 0-10oC, water (880 ml) was added stirred for around 1 hour. Solid was filtered, washed with water (200 ml) and then dried under vacuum. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to afford the title compound (2.6 g, 14.82% yield) as a yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.68 (d, J = 2.5 Hz, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.42 (d, J = 8.5 Hz, 1H), 8.0 (dd, J = 9.0, 3.0 Hz, 1H), 7.47 (s, 1H), 7.43 (s, 1H), 6.94 (d, J = 5.0 Hz, 1H), 3.96 (s, 3H), 3.90 (s, 3H); ES-MS: m / z 328.09 (M+H)+. Step 2: Synthesis of 5-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-2-amine: To a stirred solution of 6,7-dimethoxy-4-((6-nitropyridin-3-yl)oxy)quinoline (step 1, 2.5 g, 7.638 mmol, 1.0 eq) in Methanol (12.5 ml) and water (2.5 ml) was added Iron powder (2.133 g, 38.19 mmol, 5.0 eq) and acetic acid (2.5 ml). The reaction mixture was stirred at 55- 60oC for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was allowed to cool to room temperature. Ethyl acetate (50 ml) was added to the reaction mass, stirred at room temperature for 30 minutes. Reaction mass was filtered through celite bed, washed with ethyl acetate (50 ml). The filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, and the aqueous layer was extracted with ethyl acetate (50 ml). The combined organic layer was washed with water (50 ml) and brine solution (50 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Methyl-tert- butyl ether (25 ml) was to the resulting solid, stirred at room temperature for 5 hours. Solid was filtered, washed with Methyl-tert-butyl ether (5 ml) and then dried under vacuum to obtain the title compound (1.8 g, yield: 79.29%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.45 (d, J = 5.5 Hz, 1H), 7.89 (d, J = 3.0 Hz, 1H), 7.51 (s, 1H), 7.37 (s, 1H), 7.36 (d, J = 3.0 Hz, 1H), 6.56 (d, J = 9.0 Hz, 1H), 6.42 (d, J = 5.5 Hz, 1H), 6.05 (s, 2H), 3.94 (s, 6H); ES-MS: m / z 320.13 (M+Na)+. Intermediate 52: of racemic 2,2-dimethyl-3-((5-methylthiazol-2- yl)carbamoyl)cyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (6 g, 42.81 mmol, 1.0 eq) in THF (30 ml) was added 5-methylthiazol-2-amine (4.89 g, 42.81 mmol, 1.0 eq) dissolved in THF (30 ml) dropwise over a period of 15 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (120 ml) was added to the residue, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (25 ml) and then dried under vacuum to obtain the title compound (8.82 g, yield: 81%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.05 (s, 1H), 12.0 (s, 1H), 7.09 (s, 1H), 2.31 (d, J = 1.0 Hz, 3H), 2.06 (d, J = 9.5 Hz, 1H), 1.94 (d, J = 9.0 Hz, 1H), 1.30 (s, 3H), 1.17 (s, 3H); ES-MS: m / z 255.08 (M+H)+. Intermediate 53: Preparation of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl 4- methylbenzenesulfonate: To an ice cooled solution of (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol (0.500 g, 3.842 mmol, 1.0 eq) in DCM (10 ml) was added triethylamine (1.07 ml, 7.684 mmol, 2.0 eq), DMAP (0.047 g, 0.384 mmol, 0.1 eq) and para-Toluene sulfonyl chloride (0.878 g, 4.61 mmol, 1.2 eq). Cooling bath was removed, and the reaction mass was stirred at room temperature for around 5 hours. After completion of the reaction monitored by TLC, reaction mass was diluted with DCM (50 ml), washed with water (30 ml) and brine solution (20 ml). Organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure. Crude compound was purified by column chromatography using dichloromethane as an eluent to afford the product (0.920 g, yield: 84.25%) as a liquid.1H NMR (500 MHz, DMSO-d6): δ ppm7.84 (d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 5.57 (d, J = 5.0 Hz, 1H), 5.02-4.98 (m, 1H), 3.84-3.75 (m, 2H), 3.70-3.61 (m, 2H), 2.93 (dd, J = 7.5, 2.0 Hz, 1H), 2.43 (s, 3H), 1.89- 1.88 (m, 1H), 1.73-1.71 (m, 1H); ES-MS: m / z 307.06 (M+Na)+. Intermediate 54: Preparation of racemic 3-(benzo[d]thiazol-2-ylcarbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid: To a solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (10 g, 71.35 mmol, 1.0 eq) in THF (60 ml) was added benzo[d]thiazol-2-amine (10.71 g, 71.35 mmol, 1.0 eq) dissolved in THF (40 ml) dropwise over a period of 20 minutes. Reaction mass was stirred at 50-60oC for around 7 hours. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (200 ml) was added to the residue, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum to obtain the title compound (15.74 g, yield: 76%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.45 (s, 1H), 12.11 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.42 (dd, J = 15.0, 1.0 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 2.15 (d, J = 9.5 Hz, 1H), 2.01 (d, J = 9.5 Hz, 1H), 1.34 (s, 3H), 1.20 (s, 3H); ES-MS: m / z 291.10 (M+H)+. Intermediate 55: Preparation of racemic 2,2-dimethyl-3-(phenylcarbamoyl)cyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (10 g, 71.35 mmol, 1.0 eq) in THF (50 ml) was added aniline (6.645 g, 6.51 ml, 71.35 mmol, 1.0 eq) mixed in THF (50 ml) dropwise over a period of 20 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (200 ml) was added to the residue, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum to obtain the title compound (13.65 g, yield: 82%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.19 (s, 1H), 10.10 (s, 1H), 7.55 (d, J = 8.0 Hz, 2H), 7.27 (t, J = 8.0 Hz, 2H), 7.01 (t, J = 7.5 Hz, 1H), 2.0 (d, J = 9.5 Hz, 1H), 1.88 (d, J = 9.5 Hz, 1H), 1.32 (s, 3H), 1.19 (s, 3H); ES-MS: m / z 256.10 (M+Na)+. Intermediate 56: Preparation of (tetrahydro-2H-pyran-4-yl)methyl 4- methylbenzenesulfonate: To an ice cooled solution of (tetrahydro-2H-pyran-4-yl)methanol (6 g, 51.65 mmol, 1.0 eq) in DCM (48 ml) and pyridine (25 ml) was added 4-(dimethylamino)pyridine (0.315 g, 2.578 mmol, 0.05 eq) followed by para-Toluene sulfonyl chloride (9.84 g, 51.61 mmol, 1.0 eq). The mixture was allowed to stir at ambient temperature for 16 hours then was quenched with 5% aqueous HCl (18 ml) and the layers were separated. The aqueous phase was extracted with DCM (3x40 ml). The combined organic extracts were dried over sodium sulphate, filtered and concentrated under reduced pressure. The obtained compound was purified by silica gel column chromatography using DCM as an eluent to afford the title compound (8.27 g, yield: 59.24%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.79 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.87 (d, J = 6.0 Hz, 2H), 3.78 (dd, J = 11.0, 3.5 Hz, 2H), 3.22 (td, J = 12.0, 1.5 Hz, 2H), 2.42 (s, 3H), 1.87-1.82 (m, 1H), 1.47 (d, J = 13.0 Hz, 2H), 1.17-1.09 (m, 2H); ES-MS: m / z 293.07 (M+Na)+. Intermediate 57: of 2-(tert-butoxy)ethyl 4-methylbenzenesulfonate: To an ice cooled solution of 2-(tert-butoxy)ethan-1-ol (4 g, 33.84 mmol, 1.0 eq) in DCM (40 ml) was added triethylamine (9.23 ml, 67.69 mmol, 2.0 eq), 4- (dimethylamino)pyridine (0.413 g, 3.384 mmol, 0.1 eq) followed by para-Toluene sulfonyl chloride (9.678 g, 50.76 mmol, 1.5 eq). The reaction mixture was allowed to stir at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was diluted with DCM (60 ml), washed with saturated ammonium chloride solution (40 ml) and water (40 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0-40% ethyl acetate in hexanes gradient to afford the title compound (3 g, yield: 32.54%) as a colourless oil.1H NMR (500 MHz, DMSO-d6): δ ppm 7.77 (d, J = 8.0 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 4.05 (t, J = 4.5 Hz, 2H), 3.45 (t, J = 4.5 Hz, 2H), 2.42 (s, 3H), 1.05 (s, 9H). Intermediate 58: Step 1: Synthesis of 6,7-dimethoxy-4-((5-nitropyrimidin-2-yl)oxy)quinoline: To a solution of 6,7-dimethoxyquinolin-4-ol (5 g, 24.36 mmol, 1.0 eq) in DMF (50 ml) was added triethylamine (4.07 ml, 29.23 mmol, 1.2 eq ) and 2-chloro-5-nitropyrimidine (3.88 g, 24.36 mmol, 1.0 eq). The reaction mass was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. Reaction mass was poured into water (500 ml), stirred at room temperature for around 1 hour. Solid was filtered, washed with water (25 ml) and then dried under vacuum. Methanol (25 ml) was added to the obtained wet solid, stirred at room temperature for around 1 hour. Solid was filtered, washed with methanol (5 ml) and then dried under vacuum to obtain the title compound (4.2 g, yield: 52.56%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 9.75 (s, 2H), 8.58 (d, J = 8.0 Hz, 1H), 7.91 (s, 1H), 7.57 (s, 1H), 6.30 (d, J = 8.5 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H); ES-MS: m / z 329.08 (M+H)+. Step 2: Synthesis of 2-((6,7-dimethoxyquinolin-4-yl)oxy)pyrimidin-5-amine: To a stirred suspension of 6,7-dimethoxy-4-((5-nitropyrimidin-2-yl)oxy)quinoline (Step 1, 4.0 g, 12.18 mmol, 1.0 eq) in Methanol (40 ml) and water (8 ml) was added Iron powder (3.40 g, 60.92 mmol, 5.0 eq) and acetic acid (4 ml). The reaction mass was stirred at 60-65oC for around 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mass was allowed to cool to room temperature. DCM (80 ml) was added to the reaction mass, stirred at room temperature for around 30 minutes. Reaction mass was filtered through celite bed, washed with DCM (80 ml). The filtrate was basified to around pH 8.0 with 10% sodium bicarbonate solution. Organic layer was separated, and the aqueous layer was extracted with DCM (2x50 ml). The combined organic layer was washed with water (60 ml) and brine solution (60 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Methanol (32 ml) was to the resulting solid, stirred at room temperature for around 2 hours. Solid was filtered, washed with methanol (8 ml) and then dried under vacuum to obtain the title compound (2.65 g, yield: 73%) as a pale-yellow solid.1H NMR (500 MHz, DMSO-d6): δ ppm 8.27 (s, 2H), 8.07 (s, 1H), 7.56 (s, 1H), 7.05 (s, 1H), 6.11 (s, 1H), 6.02 (s, 2H), 3.89 (s, 3H), 3.82 (s, 3H); ES-MS: m / z 321.10 (M+Na)+. Intermediate 59: Preparation of (3-methyloxetan-3-yl)methyl 4-methylbenzenesulfonate: To an ice cooled solution of (3-methyloxetan-3-yl)methanol (5.0 g, 48.95 mmol, 1.0 eq) in DCM (60 ml) was added triethylamine (10.19 ml, 73.43 mmol, 1.5 eq) and para- Toluene sulfonyl chloride (10.26 g, 53.85 mmol, 1.1 eq). Cooling bath was removed, and the reaction mass was stirred at room temperature for around 3 hours. After completion of the reaction monitored by TLC, reaction mass was diluted with DCM (100 ml), washed with water (50 ml) and brine solution (30 ml). Organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure. Crude compound was purified by column chromatography using dichloromethane as an eluent to afford the title compound (6.76 g, yield: 53.87%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.82 (d, J = 8.5 Hz, 2H), 7.50 (d, J = 8.0 Hz, 2H), 4.25 (d, J = 6.0 Hz, 2H), 4.19 (d, J = 6.0 Hz, 2H), 4.11 (s, 2H), 2.43 (s, 3H), 1.19 (s, 3H); ES-MS: m / z 255.20 (M-H)-. Intermediate 60: Preparation of (S)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate: To an ice cooled solution of (S)-tetrahydrofuran-3-ol (3.0 g, 34.04 mmol, 1.0 eq) in DCM (30 ml) was added triethylamine (9.5 ml, 68.09 mmol, 2.0 eq) and para-Toluene sulfonyl chloride (7.14 g, 37.45 mmol, 1.1 eq). Cooling bath was removed, and the reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was diluted with DCM (70 ml) and washed with water (40 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by silica gel column chromatography (silica gel, 15% ethyl acetate in hexane) to afford the title compound (3.5 g, yield: 42.42%) as a liquid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.81 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 5.12 (t, J = 4.0 Hz, 1H), 3.77-3.64 (m, 4H), 2.43 (s, 3H), 2.08-2.05 (m, 1H), 1.91-1.86 (m, 1H); ES-MS: m / z 265.12 (M+Na)+. Intermediate 61: Preparation of (S)-oxetan-2-ylmethyl 4-methylbenzenesulfonate: To an ice cooled solution of (S)-oxetan-2-ylmethanol (0.500 g, 5.674 mmol, 1.0 eq) in DCM (10 ml) and THF (2 ml) was added triethylamine (1.18 ml, 8.511 mmol, 1.5 eq), DMAP (0.069 g, 0.567 mmol, 0.1 eq) and para-Toluene sulfonyl chloride (1.19 g, 6.241 mmol, 1.1 eq). Cooling bath was removed, and the reaction mass was stirred at room temperature for overnight. Reaction mass was diluted with DCM (50 ml) and washed with water (30 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by silica gel column chromatography using dichloromethane as an eluent to afford the title compound (1.36 g) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 7.81 (d, J = 8.0 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 4.83-4.80 (m, 1H), 4.43 (dd, J = 14.0, 6.5 Hz, 1H), 4.35-4.31 (m, 1H), 4.16 (dd, J = 11.5, 5.5 Hz, 1H), 4.10 (dd, J = 11.5, 3.0 Hz, 1H), 2.60-2.57 (m, 1H), 2.42 (s, 3H), 2.38-2.34 (m, 1H); ES-MS: m / z 265.11 (M+Na)+. Intermediate 62: Preparation of 2,2-dimethyl-3-(quinoxalin-6-ylcarbamoyl)cyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (6 g, 42.81 mmol, 1.0 eq) in THF (40 ml) was added quinoxalin-6-amine (6.215 g, 42.81 mmol, 1.0 eq) mixed in THF (40 ml) dropwise over a period of 20 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (60 ml) was added to the residue, extracted with DCM (3x50 ml). The combined organic layer was again washed with water (50 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (11.2 g, yield: 91.7%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.10 (s, 1H), 10.57 (s, 1H), 8.86 (s, 1H), 8.79 (s, 1H), 8.47 (s, 1H), 8.02 (d, J = 9.0 Hz, 1H), 7.90 (dd, J = 9.0, 2.0 Hz, 1H), 2.10 (d, J = 9.0 Hz, 1H), 1.96 (d, J = 9.5 Hz, 1H), 1.37 (s, 3H), 1.23 (s, 3H); ES-MS: m / z 308.11 (M+Na)+. Intermediate 63: Preparation of 2,2-dimethyl-3-(quinolin-3-ylcarbamoyl)cyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (3.79 g, 27.05 mmol, 1.0 eq) in THF (35 ml) was added quinolin-3-amine (3 g, 20.80 mmol, 1.0 eq) mixed in THF (40 ml) dropwise over a period of 20 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. THF was evaporated under reduced pressure. Water (60 ml) was added to the residue, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (30 ml) and then dried under vacuum to obtain the title compound (4.44 g, yield: 73%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.10 (s, 1H), 10.55 (s, 1H), 8.87 (d, J = 2.5 Hz, 1H), 8.69 (d, J = 2.0 Hz, 1H), 7.92 (dd, J = 13.0, 8.0 Hz, 2H), 7.61 (dd, J = 14.0, 7.0 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 2.10 (d, J = 9.5 Hz, 1H), 1.96 (d, J = 9.5 Hz, 1H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 285.14 (M+H)+. Intermediate 64: Preparation of 2,2-dimethyl-3-(pyridin-3-ylcarbamoyl)cyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (10 g, 71.35 mmol, 1.0 eq) in THF (50 ml) was added pyridin-3-amine (6.716 g, 71.35 mmol, 1.0 eq) mixed in THF (50 ml) dropwise over a period of 20 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. THF was evaporated under reduced pressure. Water (150 ml) was added to the residue, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (100 ml) and then dried under vacuum to obtain the title compound (12.5 g, yield: 74.8%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.09 (s, 1H), 10.26 (s, 1H), 8.69 (d, J = 3.0 Hz, 1H), 8.22 (dd, J = 4.5, 1.5 Hz, 1H), 8.0 (dd, J = 8.5, 1.5 Hz, 1H), 7.30 (dd, J = 8.5, 4.5 Hz, 1H), 2.02 (d, J = 9.5 Hz, 1H), 1.90 (d, J = 9.0 Hz, 1H), 1.33 (s, 3H), 1.19 (s, 3H); ES-MS: m / z 233.07 (M-H)-. Intermediate 65: Preparation of 2,2-dimethyl-3-(naphthalen-1-ylcarbamoyl)cyclopropane-1- carboxylic acid: To a stirred solution of 6,6-dimethyl-3-oxabicyclo[3.1.0]hexane-2,4-dione (10 g, 71.35 mmol, 1.0 eq) in THF (150 ml) was added naphthalen-1-amine (10.2 g, 71.35 mmol, 1.0 eq) mixed in THF (100 ml) dropwise over a period of 20 minutes. Reaction mass was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. THF was evaporated under reduced pressure. Water (300 ml) was added to the residue, stirred at room temperature for around 1 hour. Solid was filtered, washed with water (100 ml) and then dried under vacuum to obtain the title compound (14.55 g, yield: 72%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 12.39 (s, 1H), 10.18 (s, 1H), 8.10 (d, J = 4.5 Hz, 1H), 7.93 (d, J = 5.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 7.0 Hz, 1H), 7.54-7.53 (m, 3H), 2.25 (d, J = 9.5 Hz, 1H), 1.95 (d, J = 9.0 Hz, 1H), 1.38 (s, 3H), 1.26 (s, 3H); ES-MS: m / z 306.11 (M+Na)+. EXAMPLES Example 1: Preparation of N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4- (4-fluorophenyl)fumaramide: To a stirred solution of (E)-4-((4-fluorophenyl)amino)-4-oxobut-2-enoic acid (Intermediate 20, 1.3 g, 6.362 mmol, 2.0 eq) in DMF (20 ml) was added HATU (2.419 g, 6.362 mmol, 2.0 eq) and N-ethyl-N-isopropylpropan-2-amine (1.02 g, 1.3 ml, 7.953 mmol, 2.5 eq). The reaction mass stirred at room temperature for about 30 minutes. 4-((6,7- dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 1 g, 3.181 mmol, 1.0 eq) was added, stirred at room temperature for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. Reaction mass cooled to 10-20 °C, water (200 ml) was added, stirred at 10-20 °C for about 1 hour. Solid was filtered, washed with water (100 ml) and then dried under vacuum. The crude solid was purified by silica gel column chromatography using 0-10% methanol in dichloromethane gradient to obtain the product (0.550 g, yield: 34.2%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.9 (s, 1H), 10.62 (s, 1H), 8.485 (d, J = 5.5 Hz, 1H), 7.97 (dd, J = 13.0, 2.0 Hz, 1H), 7.74-7.71 (m, 2H), 7.53-7.46 (m, 3H), 7.41 (s, 1H), 7.24-7.17 (m, 4H), 6.48 (d, J = 5.0 Hz, 1H), 3.95 (s, 6H). Example 2: Preparation of N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)maleamide: To a stirred solution of (Z)-4-((4-fluorophenyl)amino)-4-oxobut-2-enoic acid (Intermediate 21, 1.33 g, 6.363 mmol, 2.0 eq) in N-methyl-2-pyrrolidone (10 ml) was added 4-dimethylaminopyridine (0.116 g, 0.954 mmol, 0.3 eq) and 4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluoroaniline (Intermediate 10, 1.0 g, 3.18 mmol, 1.0 eq). The reaction mass stirred at room temperature for about 10 minutes. Reaction mass cooled to 0 °C, 1- propanephosphonic anhydride (T3P) (4.048 ml, 6.36 mmol, 2.0 eq, 50% in ethyl acetate) solution was added, stirred at 0-10 °C for about 2 hours. Cooling bath was removed and the reaction mass stirred at room temperature for overnight. Ethyl acetate was evaporated under reduced pressure. Reaction mass cooled to 0-10 °C, 5% sodium bicarbonate solution (150 ml) was added, stirred at same temperature for about 30 minutes. Cooling bath was removed, reaction mass stirred at room temperature for about 2 hours. Solid was filtered, washed with water (20 ml) and dried. Wet solid was stirred with water (30 ml) at room temperature for about 1 hour. Solid was filtered, washed with water (10 ml) and then dried under vacuum. Methanol (30 ml) was added to the above wet solid, stirred at room temperature for about 2 hours. Solid was filtered, washed with methanol (2 ml) and then dried under vacuum to obtain the title compound (0.310 g, yield: 19.37%) as a pale green solid.1H NMR (500 MHz, DMSO- d6): δ ppm 10.74 (s, 1H), 10.45 (s, 1H), 8.485 (d, J = 5.0 Hz, 1H), 7.89 (dd, J = 14.0, 2.0 Hz, 1H), 7.67-7.64 (m, 2H), 7.54 (s, 1H), 7.48-7.42 (m, 2H), 7.41 (s, 1H), 7.17 (t, J = 9.0 Hz, 2H), 6.51-6.46 (m, 3H), 3.95 (s, 6H); ES-MS: m / z 506.4 (M+H)+. Example 3: Preparation of N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)succinamide: A solution of 4-((4-fluorophenyl)amino)-4-oxobutanoic acid (Intermediate 22, 1.343 g, 6.362 mmol, 2.0 eq) in DMF (10 ml) cooled to 0 °C. N-Ethyl diisopropyl amine (1.028 g, 1.38 ml, 7.953 mmol, 2.5 eq) and HATU (2.42 g, 6.362 mmol, 2.0 eq) were added to the reaction mass, stirred at 0 °C for about 1 hour. 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluoroaniline (Intermediate 10, 1.0 g, 3.181 mmol, 1.0 eq) was added to the reaction mass and allowed to stir at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Water (150 ml) was added to the reaction mass, stirred at 0 °C for 30 minutes. Solid was filtered, washed with water (100 ml) and then dried under vacuum. The obtained compound was purified by column chromatography (silica gel, 60-120 mesh) using 0-4% methanol in dichloromethane gradient to afford the product (0.070 g) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.37 (s, 1H), 10.07 (s, 1H), 8.49 (d, J = 5.5 Hz, 1H), 7.88 (d, J = 14.0 Hz, 1H), 7.62-7.59 (m, 2H), 7.54 (s, 1H), 7.42-7.41 (m, 3H), 7.13 (t, J = 9.0 Hz, 2H), 6.47 (d, J = 5.5 Hz, 1H), 3.955 (s, 3H), 3.953 (s, 3H), 2.69-2.67 (m, 4H); ES-MS: m / z 508.13 (M+H)+. Example 4 and Example 4a: Preparation of (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)cyclopropane-1,2-dicarboxamide and (1S,2R)- N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopropane-1,2-dicarboxamide: To a stirred solution of 2-((4-fluorophenyl)carbamoyl)cyclopropane-1-carboxylic acid (Intermediate 23, 1.7 g, 7.636 mmol, 1.2 eq) in N-methyl-2-pyrrolidone (20 ml) was added 4- dimethylaminopyridine (0.233 g, 1.909 mmol, 0.3 eq) and 4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluoroaniline (Intermediate 10, 2 g, 6.363 mmol, 1.0 eq). The reaction mass stirred at room temperature for about 10 minutes. Reaction mass cooled to 0 °C, 1- propanephosphonic anhydride (T3P) (8.1 ml, 12.72 mmol, 2.0 eq, 50% in ethyl acetate) solution was added, stirred at 0-10 °C for about 2 hours. Cooling bath was removed and the reaction mass stirred at room temperature for overnight. Ethyl acetate was evaporated under reduced pressure. Reaction mass cooled to 0-10 °C, 5% sodium bicarbonate solution (300 ml) was added, stirred at same temperature for about 30 minutes. Cooling bath was removed, reaction mass stirred at room temperature for about 2 hours. Solid was filtered, washed with water (50 ml) and dried. Wet solid was stirred with water (60 ml) at room temperature for about 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum. Methanol (60 ml) was added to the above wet solid, stirred at room temperature for about 2 hours. Solid was filtered, washed with methanol (6 ml) and then dried under vacuum to obtain the product (1.72 g, yield: 52%) as an off-white solid. The enantiomers of the resulted compound were separated by Preparative chiral HPLC. The first isomer was eluted in chiral HPLC and the eluent was concentrated to obtain the product (0.180 g) as an off-white solid. Isomer-I: Enantiomeric purity by chiral HPLC: 99.97%;1H NMR (500 MHz, CD3OD): δ ppm 8.31 (d, J = 5.5 Hz, 1H), 7.67 (dd, J = 13.0, 2.5 Hz, 1H), 7.53 (s, 1H), 7.43 (dd, J = 9.0, 5.0 Hz, 2H), 7.29-7.25 (m, 2H), 7.19 (t, J = 8.5 Hz, 1H), 6.92 (t, J = 9.0 Hz, 2H), 6.39 (d, J = 5.5 Hz, 1H), 3.91 (s, 3H), 3.91 (s, 3H), 2.17 (dd, J = 8.0, 6.5 Hz, 2H), 1.66-1.65 (m, 1H), 1.27 (dd, J = 9.0, 3.5 Hz, 1H); ES-MS: m / z 520.15 (M+H)+. The second isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.110 g), as an off-white solid. Isomer-2: Enantiomeric purity by chiral HPLC: 99.17%;1H NMR (500 MHz, CD3OD): δ ppm 8.31 (d, J = 5.5 Hz, 1H), 7.67 (dd, J = 13.0, 2.5 Hz, 1H), 7.53 (s, 1H), 7.43 (dd, J = 9.0, 5.0 Hz, 2H), 7.29-7.35 (m, 2H), 7.19 (t, J = 9.0 Hz, 1H), 6.92 (t, J = 9.0 Hz, 2H), 6.39 (d, J = 5.5 Hz, 1H), 3,91 (s, 3H), 3.91 (s, 3H), 2.17 (dd, J = 8.0, 6.5 Hz, 2H), 1.66-1.65 (m, 1H), 1.27 (dd, J = 8.5, 3.5 Hz, 1H); ES-MS: m / z 520.20 (M+H)+. Example 5 and Example 5a: Preparation of (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)cyclobutane-1,2-dicarboxamide and (1S,2R)- N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)cyclobutane- 1,2-dicarboxamide: To a stirred solution of 2-((4-fluorophenyl)carbamoyl)cyclobutane-1-carboxylic acid (Intermediate 24, 2.7 g, 11.45 mmol, 1.2 eq) in N-methyl-2-pyrrolidone (30 ml) was added 4- dimethylaminopyridine (0.349 g, 2.86 mmol, 0.3 eq) and 4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluoroaniline (Intermediate 10, 3 g, 9.545 mmol, 1.0 eq). The reaction mass stirred at room temperature for about 10 minutes. Reaction mass cooled to 0 °C, 1- propanephosphonic anhydride (T3P) (12.15 ml, 19.09 mmol, 2.0 eq, 50% in ethyl acetate) solution was added, stirred at 0-10 °C for about 2 hours. Cooling bath was removed and the reaction mass stirred at room temperature for overnight. Ethyl acetate was evaporated under reduced pressure. Reaction mass cooled to 0-10 °C, 5% sodium bicarbonate solution (450 ml) was added, stirred at same temperature for about 30 minutes. Cooling bath was removed, reaction mass stirred at room temperature for about 2 hours. Solid was filtered, washed with water (50 ml) and dried. Wet solid was stirred with water (60 ml) at room temperature for about 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum. Methanol (75 ml) was added to the above wet solid, stirred at room temperature for about 2 hours. Solid was filtered, washed with methanol (6 ml) and dried under vacuum to obtain the product (3.7 g, yield: 72.66%) as a pale-yellow solid. The enantiomers of the resulted compound were separated by Preparative chiral HPLC. The first isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.060 g) as an off-white solid. Isomer-1: Enantiomeric purity by chiral HPLC: 99.76%.1H NMR (500 MHz, DMSO-d6): δ ppm 9.88 (s, 1H), 9.61 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 7.77 (d, J = 12.5 Hz, 1H), 7.53 (dd, J = 9.0, 5.0 Hz, 2H), 7.51 (s, 1H), 7.40 (s, 1H), 7.35 (d, J = 7.0 Hz, 2H), 7.08 (t, J = 9.0 Hz, 2H), 6.38 (d, J = 5.0 Hz, 1H), 3.94 (s, 3H), 3.94 (s, 3H), 3.54 (m, 2H), 2.36-2.32 (m, 2H), 2.15-2.13 (m, 2H); ES-MS: m / z 556.24 (M+Na)+. The second isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.300 g), as an off-white solid. Isomer-2: Enantiomeric purity by chiral HPLC: 99.98%.1H NMR (500 MHz, DMSO-d6): δ ppm 9.88 (s, 1H), 9.61 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 7.77 (d, J = 13.0 Hz, 1H), 7.53 (dd, J = 9.0, 5.0 Hz, 2H), 7.51 (s, 1H), 7.40 (s, 1H), 7.35 (d, J = 7.0 Hz, 2H), 7.09 (t, J = 8.5 Hz, 2H), 6.37 (d, J = 5.0 Hz, 1H), 3.94 (s, 3H), 3.94 (s, 3H), 3.54 (m, 2H), 2.34-2.33 (m, 2H), 2.16-2.15 (m, 2H); ES-MS: m / z 534.21 (M+H)+. Example 6 and Example 6a: Preparation of (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)cyclopentane-1,2-dicarboxamide and (1S,2R)- N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopentane-1,2-dicarboxamide: To a stirred solution of 2-((4-fluorophenyl)carbamoyl)cyclopentane-1-carboxylic acid (Intermediate 25, 2.87 g, 11.45 mmol, 1.2 eq) in N-methyl-2-pyrrolidone (30 ml) was added 4-dimethylaminopyridine (0.35 g, 2.862 mmol, 0.3 eq) and 4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluoroaniline (Intermediate 10, 3 g, 9.54 mmol, 1.0 eq). The reaction mass stirred at room temperature for 10 minutes. Reaction mass cooled to 0 °C, 1-propanephosphonic anhydride (T3P) (12.14 ml, 19.08 mmol, 2.0 eq, 50% in ethyl acetate) solution was added, stirred at 0-10 °C for 2 hours. Cooling bath was removed and the reaction mass stirred at room temperature for overnight. Ethyl acetate was evaporated under reduced pressure. Reaction mass cooled to 0-10 °C, 5% sodium bicarbonate solution (300 ml) was added, stirred at same temperature for 30 minutes. Cooling bath was removed, reaction mass stirred at room temperature for 2 hours. Solid was filtered, washed with water (50 ml) and dried. Wet solid was stirred with water (40 ml) at room temperature for 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum. Methanol (15 ml) was added to the above wet solid, stirred at room temperature for 2 hours. Solid was filtered, washed with methanol (6 ml) and then dried under vacuum to obtain the product (1.96 g, yield: 37.5%) as an off-white solid. The enantiomers of the resulted compound were separated by Preparative chiral HPLC. The first isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.120 g) as an off-white solid. Isomer-1: Chemical purity by HPLC: 98.17%, enantiomeric purity by chiral HPLC: 99.75%.1H NMR (500 MHz, DMSO-d6): δ ppm 10.07 (d, 1H), 8.45 (d, J = 5.0 Hz, 1H), 7.74 (d, J = 13.0 Hz, 1H), 7.52-7.51 (m, 3H), 7.40 (s, 1H), 7.34-7.32 (m, 2H), 7.07 (t, J = 8.5 Hz, 2H), 6.35 (d, J = 4.5 Hz, 1H), 3.94 (s, 3H), 3.94 (s, 3H), 2.82-2.80 (m, 2H), 2.03-1.91 (m, 5H), 1.66-1.62 (m, 1H); ES-MS: m / z 548.20 (M+H)+. The second isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.230 g), as an off-white solid. Isomer-2: Enantiomeric purity by chiral HPLC: 98.24%.1H NMR (500 MHz, DMSO-d6): δ ppm 10.09 (d, 1H), 8.45 (d, J = 5.0 Hz, 1H), 7.73 (d, J = 12.5 Hz, 1H), 7.52-7.50 (m, 3H), 7.39 (s, 1H), 7.35-7.30 (m, 2H), 7.05 (t, J = 8.0 Hz, 2H), 6.32 (d, J = 4.5 Hz, 1H), 3.94 (s, 3H), 3.93 (s, 3H), 2.81 (m, 2H), 2.03-1.90 (m, 5H), 1.61-1.60 (m, 1H); ES-MS: m / z 548.19 (M+H)+. Example 7 Example 7a: Preparation of (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)cyclohexane-1,2-dicarboxamide and (1S,2R)-N1-(4- ((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)cyclohexane-1,2- dicarboxamide: To a stirred solution of 2-((4-fluorophenyl)carbamoyl)cyclohexane-1-carboxylic acid (Intermediate 26, 2.02 g, 7.636 mmol, 1.2 eq) in N-methyl-2-pyrrolidone (20 ml) was added 4-dimethylaminopyridine (0.233 g, 1.909 mmol, 0.3 eq) and 4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluoroaniline (Intermediate 10, 2 g, 6.363 mmol, 1.0 eq). The reaction mass stirred at room temperature for 10 minutes. Reaction mass cooled to 0 °C, 1-propanephosphonic anhydride (T3P) (8.1 ml, 12.72 mmol, 2.0 eq, 50% in ethyl acetate) solution was added, stirred at 0-10 °C for 2 hours. Cooling bath was removed and the reaction mass stirred at room temperature for overnight. Ethyl acetate was evaporated under reduced pressure. Reaction mass cooled to 0-10 °C, 5% sodium bicarbonate solution (300 ml) was added, stirred at same temperature for 30 minutes. Cooling bath was removed, reaction mass stirred at room temperature for 2 hours. Solid was filtered, washed with water (50 ml) and dried. Wet solid was stirred with water (60 ml) at room temperature for 1 hour. Solid was filtered, washed with water (20 ml) and then dried under vacuum. Methanol (10 ml) was added to the above wet solid, stirred at room temperature for 2 hours. Solid was filtered, washed with methanol (6 ml) and then dried under vacuum to obtain the product (1.9 g, yield: 53%) as a pale-yellow solid. The enantiomers of the resulted compound were separated by Preparative chiral HPLC. The first isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.120 g) as an off-white solid. Isomer-1: Enantiomeric purity by chiral HPLC: 98.01%;1H NMR (500 MHz, DMSO-d6): δ ppm 9.99 (s, 1H), 9.71 (s, 1H), 8.45 (d, J = 5.5 Hz, 1H), 7.85 (dd, J = 13.5, 2.0 Hz, 1H), 7.58 (dd, J = 9.0, 5.0 Hz, 2H), 7.52 (s, 1H), 7.42-7.35 (m, 3H), 7.10 (t, J = 9.0 Hz, 2H), 6.43 (d, J = 5.5 Hz, 1H), 3.94 (s, 6H), 2.83-2.79 (m, 2H), 2.21-2.16 (m, 2H), 1.76-1.73 (m, 4H), 1.42 (m, 2H); ESI-MS: 562.26 (M+H)+. The second isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.082 g), as an off-white solid. Isomer-2: Enantiomeric purity by chiral HPLC: 99.82%;1H NMR (500 MHz, DMSO-d6): δ ppm 10.02 (s, 1H), 9.73 (s, 1H), 8.45 (d, J = 5.5 Hz, 1H), 7.85 (dd, J = 13.5, 2.0 Hz, 1H), 7.58 (dd, J = 9.0, 5.0 Hz, 2H), 7.52 (s, 1H), 7.40-7.37 (m, 3H), 7.09 (t, J = 9.0 Hz, 2H), 6.42 (d, J = 5.5 Hz, 1H), 3.94 (s, 6H), 2.84-2.80 (m, 2H), 2.19 (m, 2H), 1.75 (m, 4H), 1.42 (m, 2H); ESI-MS: 562.26 (M+H)+. Example 8: Preparation of (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of compound (1R,3S)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 2, 1.7 g, 1.0 eq.] in N-methyl pyrrolidone (NMP) (20 vol) was added diisopropyl ethyl amine (2.33 mL, 2.0 eq.) at room temperature and the resulting mixture was stirred for 10 min. Add 50% T3P in Ethyl acetate [6.4 mL, 1.5 eq.] to the reaction mixture, stir for 10 min and add 4-((6,7-dimethoxyquinolin- 4-yl)oxy)aniline (Intermediate 28, 2 g, 1.0 eq.) at room temperature and then stir for 2 hours. The total reaction mixture was heated to 45-50 °C and stir for overnight. After completion of reaction confirmed by TLC cool the reaction mixture to room temperature 25-27 °C, add water (20 vol) at room temperature and stir for 10 minutes. The reaction mixture was extracted with ethyl acetate twice and the organic layer was washed with 1N NaOH solution, water and brine solution. The combined organic layers were dried over sodium sulphate and evaporated to dryness (Wt: 1.0 g). HPLC Purity: 98.12%;1H NMR: CDCl3; δ 9.75 (s, NH, 1H), 9.14 (s, NH, 1H), 8.48 (d, 1H), 7.68-7.71 (m, 2H), 7.57-7.53 (m, 2H), 7.42 (s, 1H), 7.15-7.18 (d, J = 8.7 Hz, 2H), 7.01-7.18 (m, 2H), 6.45-6.47 (d, J = 8.7 Hz, 2H), 4.05 (s, 2x3H, OCH3), 1.92-2.02 (dd, J = 21 Hz, 2H), 1.44 (s, 3H, CH3), 1.43 (s, 3H, CH3). Example 9: Preparation of (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of compound (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 1.7 g, 1.0 eq) in N-methyl pyrrolidone (NMP) (20 ml) was added N-ethyl-N-isopropylpropan-2-amine (2.33 mL, 2.0 eq.) at room temperature and the resulting mixture was stirred for 10 min. Add 50% T3P in Ethyl acetate (6.4 mL, 1.5 eq.) to the reaction mixture, stir for 10 min and add 4-((6,7- dimethoxyquinolin-4-yl)oxy)aniline (Intermediate 28, 2 g, 1.0 eq.) at room temperature and then stir for 2 hours. The total reaction mixture was heated to 45-50 °C and stir for overnight. After completion of reaction confirmed by TLC, cool the reaction mixture to room temperature 25-27 °C, add water (20 vol) at room temperature and stir for 10 minutes. The reaction mixture was extracted with ethyl acetate twice and the organic layer was washed with 1N NaOH solution, water and brine solution. The combined organic layers were dried over sodium sulphate and evaporated to dryness (Wt: 1.05 g). HPLC Purity: 98.4%;1H NMR: CDCl3; δ 9.75 (s, NH, 1H), 9.12 (s, NH, 1H), 8.48 (d, 1H), 7.69-7.71 (m, 2H), 7.57-7.53 (m, 2H), 7.42 (s, 1H), 7.14-7.17 (d, J = 8.7 Hz, 2H), 7.01-7.07 (m, 2H), 6.46-6.47 (d, J = 8.7 Hz, 2H), 4.05 (s, 2x3H, OCH3), 1.93-2.02 (dd, J = 21Hz, 2H), 1.43 (s, 6H, 2xCH3). Example 10 and Example 10a: Preparation of (1S,2R)-N1-(3-chloro-4-((6,7- dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl-3,3-dimethylcyclopropane-1,2- dicarboxamide and (1R,2S)-N1-(3-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2- cyclopropyl-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 3-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline (Intermediate 9, 1.3 g, 3.930 mmol, 1.0 eq) in DCM (26 ml) at 0 ºC was added Racemic 3- (cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 1-step 1, 1.16 g, 5.895 mmol, 1.5 eq), EDC.HCl (3.39 g, 17.686 mmol, 4.5 eq) and 4- dimethylaminopyridine (0.24 g, 1.965 mmol, 0.5 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mass was diluted with DCM (100 ml), washed with water (100 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient. The obtained compound was dissolved in DCM, charcoal was added, stirred at 40 ºC for about 1 hour. Reaction mass filtered through celite bed, washed with DCM and evaporated under reduced pressure. Solid was washed with hexane and dried under vacuum to obtain the compound (1.25 g) as a solid. The enantiomers of the resulted compound were separated by Preparative chiral HPLC. The first isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (270 mg, yield: 13.5%) as an off-white solid. Isomer-I: Chemical purity by HPLC: 96.2%, enantiomeric purity by chiral HPLC: >99%.1H NMR (300 MHz, CDCl3): δ ppm 11.41 (s, 1H), 8.47 (d, J = 5.4 Hz, 1H), 7.97 (d, J = 2.4 Hz, 1H), 7.64 (d, J = 2.4 Hz, 1H), 7.61 (s, 1H), 7.42 (s, 1H), 7.18 (d, J = 8.7 Hz, 1H), 6.36 (s, 1H), 6.32 (d, J = 5.1 Hz, 1H), 4.07 (s, 3H), 4.05 (s, 3H), 2.0 (d, J = 8.4 Hz, 1H), 2.83-2.76 (m, 1H), 1.60 (d, J = 8.4 Hz, 1H), 1.36 (s, 3H), 1.35 (s, 3H), 0.88-0.85 (m, 2H), 0.61-0.58 (m, 2H). The second isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.210 g), as an off-white solid. Isomer-II: ES-MS: m / z 510.19 (M+H)+. Example 11 and Example 11a: Preparation of (1R,2S)-N1-cyclopropyl-N2-(4-((6,7- dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide and (1S,2R)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 1.4 g, 4.454 mmol, 1.0 eq) in DCM (14 ml) was added Racemic 3- (cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 1-step 1, 1.756 g, 8.908 mmol, 2.0 eq), EDC.HCl (3.415 g, 17.816 mmol, 4.0 eq) and 4- dimethylaminopyridine (0.326 g, 2.672 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mass diluted with DCM (50 ml), washed with water (30 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-4% methanol in dichloromethane gradient to obtain the product (1.1 g, yield: 50.22%) as an off-white solid. The enantiomers of the resulted compound were separated by Preparative chiral HPLC. The first isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.135 g) as an off-white solid. Isomer-I: Chemical purity by HPLC: 98.96%, enantiomeric purity by chiral HPLC: 99.59%;1H NMR (300 MHz, CDCl3): δ ppm 11.44 (s, 1H), 8.48 (d, J = 5.4 Hz, 1H), 7.84 (dd, J = 12.3, 1.8 Hz, 1H), 7.59 (s, 1H), 7.42 (s, 1H), 7.39 (d, J = 9.0 Hz, 1H), 7.18 (t, J = 8.7 Hz, 1H), 6.41 (d, J = 5.1 Hz, 1H), 6.28 (s, 1H), 4.07 (s, 3H), 4.05 (s, 3H), 2.84-2.77 (m, 1H), 2.0 (d, J = 8.4 Hz, 1H), 1.59 (d, J = 8.1 Hz, 1H), 1.37 (s, 3H), 1.35 (s, 3H), 0.88-0.85 (m, 2H), 0.59 (m, 2H). The second isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.113 g), as an off-white solid. Isomer-II: Chemical purity by HPLC: 99%, enantiomeric purity by chiral HPLC: 99.88%;1H NMR (300 MHz, CDCl3): δ ppm 11.44 (s, 1H), 8.48 (d, J = 5.1 Hz, 1H), 7.84 (dd, J = 12.3, 2.1 Hz, 1H), 7.59 (s, 1H), 7.42 (s, 1H), 7.39 (d, J = 8.1 Hz, 1H), 7.18 (t, J = 8.4 Hz, 1H), 6.41 (d, J = 5.1 Hz, 1H), 6.25 (s, 1H), 4.06 (s, 3H), 4.05 (s, 3H), 2.84-2.77 (m, 1H), 2.0 (d, J = 8.4 Hz, 1H), 1.59 (d, J = 8.4 Hz, 1H), 1.37 (s, 3H), 1.35 (s, 3H), 0.88-0.85 (m, 2H), 0.61- 0.57 (m, 2H). Example 12 and Example 12a: Preparation of (1R,2S)-N1-cyclopropyl-N2-(4-((6,7- dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide and (1S,2R)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluoroaniline (Intermediate 11, 1.5 g, 4.772 mmol, 1.0 eq) in DCM (30 ml) was added Racemic 3- (cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 1-step 1, 2.3 g, 11.93 mmol, 2.5 eq), EDC.HCl (4.1 g, 21.474 mmol, 4.5 eq) and 4- dimethylaminopyridine (0.291 g, 2.386 mmol, 0.5 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mass was diluted with DCM (200 ml), washed with water (2x100 ml) and brine solution (100 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the product (1.25 g) as an off-white solid. The enantiomers of the resulted compound were separated by Preparative chiral HPLC. The first isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.210 g) as an off-white solid. Isomer-I: Chemical purity by HPLC: 99.3%, enantiomeric purity by chiral HPLC: 99.8%;1H NMR (300 MHz, CDCl3): δ ppm 10.62 (s, 1H), 8.51 (d, J = 5.1 Hz, 1H), 8.25 (t, J = 8.7 Hz, 1H), 7.51 (s, 1H), 7.42 (s, 1H), 6.97 (d, J = 9.0 Hz, 2H), 6.65 (s, 1H), 6.51 (d, J = 5.1 Hz, 1H), 4.05 (s, 6H), 2.83-2.77 (m, 1H), 1.99 (d, J = 8.4 Hz, 1H), 1.68 (d, J = 8.4 Hz, 1H), 1.39 (s, 3H), 1.37 (s, 3H), 0.84-0.79 (m, 2H), 0.58-0.57 (m, 2H); ES-MS: m / z 494.35 (M+H)+. The second isomer was eluted in chiral HPLC, and the eluent was concentrated to obtain the product (0.200 g), as an off-white solid. Isomer-II: Chemical purity by HPLC: 99.8%, enantiomeric purity by chiral HPLC: 99.37%;1H NMR (300 MHz, CDCl3): δ ppm 10.62 (s, 1H), 8.51 (d, J = 5.4 Hz, 1H), 8.25 (t, J = 8.7 Hz, 1H), 7.51 (s, 1H), 7.42 (s, 1H), 6.97 (d, J = 9.0 Hz, 2H), 6.67 (s, 1H), 6.51 (d, J = 5.4 Hz, 1H), 4.05 (s, 6H), 2.83-2.77 (m, 1H), 1.99 (d, J = 8.7 Hz, 1H), 1.68 (d, J = 8.4 Hz, 1H), 1.39 (s, 3H), 1.37 (s, 3H), 0.84-0.82 (m, 2H), 0.57 (m, 2H); ES-MS: m / z 494.35 (M+H)+. Example 13: Preparation of (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2- methylphenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-methylaniline (Intermediate 12, 0.4 g, 1.288 mmol, 1.0 eq) in DCM (20 ml) was added (1R,3S)-3-((4- fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 2, 0.64 g, 2.577 mmol, 2.0 eq), EDC.HCl (0.987 g, 5.152 mmol, 4.0 eq), 4-dimethylaminopyridine (0.094 g, 0.772 mmol, 0.6 eq) and triethylamine (0.724 ml, 5.152 mmol, 4.0 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (50 ml) and washed with water (50 ml). The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient to obtain the title compound (0.135 g, yield: 19.28%) as an off-white solid.1H NMR (300 MHz, CDCl3): δ ppm 9.46 (s, 1H), 8.92 (s, 1H), 8.49 (d, J = 5.1 Hz, 1H), 7.78 (d, J = 9.3 Hz, 1H), 7.54 (t, J = 6.6 Hz, 3H), 7.43 (s, 1H), 7.06-6.98 (m, 4H), 6.51 (d, J = 5.4 Hz, 1H), 4.05 (s, 6H), 2.35 (s, 3H), 2.01-2.0 (m, 2H), 1.47 (s, 3H), 1.46 (s, 3H); ES-MS: m / z 544.46 (M+H)+. 4-yl)oxy)-2- dicarboxamide: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-methylaniline (Intermediate 12, 0.500 g, 1.61 mmol, 1.0 eq) in DCM (10 ml) was added (1S,3R)-3-((4- fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 1.01 g, 4.02 mmol, 2.5 eq) followed by EDC.HCl (1.23 g, 6.44 mmol, 4.0 eq) and 4- dimethylaminopyridine (0.117 g, 0.96 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. The reaction mixture was diluted with water (30 ml) and extracted with DCM (3x300 ml). The combined organic layer was washed with water (30 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient. The obtained compound was dissolved in DCM (15 ml), activated charcoal (15 mg) was added and heated to reflux for about 15 minutes. The reaction mixture was filtered through a celite bed and washed with DCM (15 ml). The filtrate was evaporated under reduced pressure. The residue was again treated with ethyl acetate (5 ml) and hexane (45 ml), stirred at room temperature for about 20 minutes. Solid was filtered, washed with hexane (5 ml) and then dried under vacuum to obtain the title compound (0.320 g, yield: 36%) as a solid. Enantiomeric purity by chiral HPLC: 99.5%.1H NMR (300 MHz, CDCl3): δ ppm 9.48 (s, 1H), 8.93 (s, 1H), 8.49 (d, J = 5.1 Hz, 1H), 7.78 (d, J = 9.6 Hz, 1H), 7.54 (t, J = 6.6 Hz, 3H), 7.42 (s, 1H), 7.05-6.98 (m, 4H), 6.51 (d, J = 5.1 Hz, 1H), 4.05 (s, 6H), 2.35 (s, 3H), 2.03-1.97 (m, 2H), 1.47 (s, 3H), 1.46 (s, 3H); ES-MS: m / z 544.46 (M+H)+. Method 1: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 0.400 g, 1.27 mmol, 1.0 eq) in DCM (10 ml) was added (1S,3R)-3-((4- fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 0.800 g, 3.181 mmol, 2.5 eq) followed by EDC.HCl (0.970 g, 5.08 mmol, 4.0 eq) and 4- dimethylaminopyridine (0.0929 g, 0.76 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. The reaction mixture was diluted with water (20 ml), organic layer was separated, and aqueous layer was extracted with DCM (3x30 ml). The combined organic layer was washed with water (30 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient. The obtained compound was further purified by treating with EtOAc (5 ml) and hexane (45 ml), stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum to obtain the title compound (0.230 g, yield: 33%) as a solid. Enantiomeric purity by chiral HPLC: 99.2%.1H NMR (300 MHz, CDCl3): δ ppm 10.60 (s, 1H), 9.01 (s, 1H), 8.48 (d, J = 5.1 Hz, 1H), 7.83 (dd, J = 12.0, 1.8 Hz, 1H), 7.59 (s, 1H), 7.55 (dd, J = 9.0 Hz, 4.8 Hz, 2H), 7.41 (s, 1H), 7.37-7.34 (m, 1H), 7.20 (t, J = 8.4 Hz, 1H), 7.05 (t, J = 8.4 Hz, 2H), 6.42 (d, J = 5.1 Hz, 1H), 4.07 (s, 3H), 4.03 (s, 3H), 2.04 (d, J = 8.4 Hz, 1H), 1.92 (d, J = 8.1 Hz, 1H), 1.43 (s, 3H), 1.40 (s, 3H); ES-MS: m / z 548.63 (M+H)+. Method 2: To a solution of (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane- 1-carboxylic acid (Intermediate 3, 0.479 g, 1.908 mmol, 1.2 eq) in DCM (10 ml) was added DMAP (0.058 g, 0.477 mmol, 0.3 eq) and 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluoroaniline (Intermediate 10, 0.500 g, 1.590 mmol, 1.0 eq). The reaction mixture was stirred at room temperature for 10 minutes, cooled to 0-10 °C, 1-propane phosphonic anhydride solution (T3P) (2.024 ml, 3.181 mmol, 2.0 eq, 50% in EtOAc) was added, stirred at same temperature for about 1 hour. Cooling bath was removed, and the reaction mass was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. Reaction mass was diluted with DCM (50 ml), cooled to 0-10 °C, pH adjusted to around 8.0 with 10% NaHCO3solution. Organic layer was separated, and the aqueous layer was extracted with DCM (2x30 ml). The combined organic layer was washed with 7% acetic acid solution (30 ml), 5% sodium bicarbonate solution (30 ml), water (30 ml) and brine solution (30 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The resulting compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to afford the title compound (0.479 g, yield: 55%) as an off-white solid. Example 16: Preparation of (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluoroaniline (Intermediate 11, 0.500 g, 1.590 mmol, 1.0 eq) in DCM (10 ml) was added (1S,3R)-3-((4- fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 1.0 g, 3.976 mmol, 2.5 eq), EDC.HCl (1.37 g, 7.158 mmol, 4.5 eq) and 4-dimethylaminopyridine (0.097 g, 0.795 mmol, 0.5 eq). The reaction mixture was stirred at room temperature for about 48 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml), washed with water (100 ml) and brine solution. The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.050 g, yield: 5.7%) as an off-white solid. Enantiomeric purity by chiral HPLC: 99.5%.1H NMR (300 MHz, CDCl3): δ ppm 9.35 (s, 1H), 9.16 (s, 1H), 8.52 (d, J = 5.4 Hz, 1H), 8.33 (t, J = 8.4 Hz, 1H), 7.58-7.50 (m, 3H), 7.44 (s, 1H), 7.06-7.0 (m, 4H), 6.53 (d, J = 5.4 Hz, 1H), 4.05 (s, 6H), 2.0 (m, 2H), 1.46 (s, 6H); ES-MS: m / z 548.56 (M+H)+. 1,2- dicarboxamide: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-methylaniline (Intermediate 12, 0.350 g, 1.127 mmol, 1.0 eq) in DCM (10 ml) was added (1S,3R)-3-((3,4- difluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 4, 0.759 g, 2.819 mmol, 2.5 eq), EDC.HCl (0.973 g, 5.075 mmol, 4.5 eq) and 4- dimethylaminopyridine (0.069 g, 0.563 mmol, 0.5 eq). The reaction mixture was stirred at room temperature for two days. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (200 ml) and washed with water (200 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.050 g, yield: 7.9%) as an off-white solid. Chemical purity by HPLC: 92.6%, enantiomeric purity by chiral HPLC: 99.5%;1H NMR (300 MHz, CDCl3): δ ppm 10.04 (s, 1H), 8.50 (d, J = 5.4 Hz, 1H), 8.45 (s, 1H), 7.79-7.65 (m, 2H), 7.54 (s, 1H), 7.48 (s, 1H), 7.16- 7.03 (m, 4H), 6.54 (d, J = 5.1 Hz, 1H), 4.06 (s, 3H), 4.05 (s, 3H), 2.35 (s, 3H), 2.06-1.97 (m, 2H), 1.47 (s, 3H), 1.45 (s, 3H); ES-MS: m / z 562.16 (M+H)+. Example 17a: Preparation of (1S,2R)-N1-(3,4-difluorophenyl)-N2-(4-((6,7- dimethoxyquinolin-4-yl)oxy)-2-methylphenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide: To a solution of (1R,3S)-3-((3,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 4a, 0.520 g, 1.933 mmol, 1.2 eq) in DCM (10 ml) was added DMAP (0.059 g, 0.483 mmol, 0.3 eq) and 4-((6,7- dimethoxyquinolin-4-yl)oxy)-2-methylaniline (Intermediate 12, 0.500 g, 1.611 mmol, 1.0 eq). Reaction mass was stirred at room temperature for 10 minutes. Reaction mass was cooled to 0-10oC, 1-propane phosphonic anhydride solution (T3P) (2.05 ml, 3.222 mmol, 2.0 eq, 50% in EtOAc) was added dropwise, stirred at same temperature for 1 hour. Cooling bath was removed, and the reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was diluted with DCM (60 ml), cooled to 0-10oC, pH adjusted to around 8.0 with 10% NaHCO3 solution. Organic layer was separated, and the aqueous layer was extracted with DCM (2x30 ml). The combined organic layer was washed with 7% acetic acid solution (20 ml), 5% sodium bicarbonate solution (30 ml), water (50 ml) and brine solution (20 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.280 g, yield: 31%) as an off-white solid. ESI-MS: m / z 584.19 (M+Na)+. Example 18: Preparation of (1S,2R)-N1-(2-chloro-4-((6,7-dimethoxyquinolin-4- yl)oxy)phenyl)-N2-cyclopropyl-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline (Intermediate 13, 0.500 g, 1.51 mmol, 1.0 eq) in DCM (10 ml) was added (1S,3R)-3- (cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 1, 1.19 g, 6.04 mmol, 4.0 eq), EDC.HCl (1.73 g, 9.06 mmol, 6 eq) and DMAP (0.221 g, 1.81 mmol, 1.2 eq). The reaction mass stirred at room temperature for about 48 hours. TLC indicated reaction did not proceed completely. Reaction mass refluxed for about 1 day. Reaction mass was diluted with water (50 ml) and extracted with DCM (3x50 ml). The combined organic layer was washed with water (50 ml) and brine solution (10 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient. The obtained compound was further purified by treating with ethyl acetate (2 ml) and hexane (20 ml), stirred at room temperature for about 30 minutes. Solid was filtered and then dried under vacuum to obtain the product (0.250 g) as a solid. Chemical purity by HPLC: 98.22%;1H NMR (300 MHz, CDCl3): δ ppm 9.73 (s, 1H), 8.51 (d, J = 5.4 Hz, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.50 (s, 1H), 7.43 (s, 1H), 7.11 (dd, J = 9.0 Hz, 2.4 Hz, 1H), 6.87 (s, 1H), 6.51 (d, J = 5.4 Hz, 1H), 4.05 (s, 6H), 2.81-2.75 (m, 1H), 1.95 (d, J = 8.7 Hz, 1H), 1.76 (d, J = 8.7 Hz, 1H), 1.42 (s, 3H), 1.38 (s, 3H), 0.84-0.79 (m, 2H), 0.58-0.55 (m, 2H); ES-MS: m / z 509.80 (M+H)+. Example 19: Preparation of (1R,2S)-N1-(2-chloro-4-((6,7-dimethoxyquinolin-4- yl)oxy)phenyl)-N2-cyclopropyl-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)aniline (Intermediate 13, 1.0 g, 3.023 mmol, 1.0 eq) in DCM (10 ml) was added (1R,3S)-3- (cyclopropylcarbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 5, 3.57 g, 18.138 mmol, 6.0 eq) followed by EDC.HCl (4.61 g, 24.184 mmol, 8.0 eq) and 4- dimethylaminopyridine (0.553 g, 4.534 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient. The obtained compound was further purified by treating with 10% ethyl acetate: hexane (25 ml), stirred at room temperature, filtered and dried under vacuum to obtain the product (0.3 g) as an off-white solid. Chemical purity by HPLC: 96.43%;1H NMR (300 MHz, CDCl3): δ ppm 9.77 (s, 1H), 8.51 (d, J = 5.1 Hz, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.50 (s, 1H), 7.43 (s, 1H), 7.26-7.22 (m, 2H), 7.10 (dd, J = 9.0, 2.7 Hz, 1H), 6.91 (s, 1H), 6.51 (d, J = 5.1 Hz, 1H), 4.05 (s, 6H), 2.82- 2.71 (m, 1H), 1.95 (d, J = 8.4 Hz, 1H), 1.76 (d, J = 8.4 Hz, 1H), 1.43 (s, 3H), 1.38 (s, 3H), 0.82-0.77 (m, 2H), 0.58-0.53 (m, 2H); ES-MS: m / z 510.0 (M+H)+. To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 1 g, 3.183 mmol, 1.0 eq) in DCM (20 ml) was added (1R,3S)-3-((4- fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 2, 2.39 g, 9.55 mmol, 3.0 eq), EDC.HCl (1.83 g, 9.55 mmol, 3.0 eq) and 4-dimethylaminopyridine (0.23 g, 1.909 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (20 ml) and washed with water (2x20 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient to obtain the title compound (0.2 g, yield: 11.76%) as an off-white solid.1H NMR (300 MHz, DMSO-d6): δ ppm 10.40 (s, 1H), 10.13 (s, 1H), 8.46 (d, J = 5.1 Hz, 1H), 7.84 (d, J = 13.5 Hz, 1H), 7.58 (dd, J = 9.0, 5.1 Hz, 2H), 7.52 (s, 1H), 7.40-7.38 (m, 3H), 7.11 (t, J = 8.7 Hz, 2H), 6.44 (d, J = 5.1 Hz, 1H), 3.94 (s, 6H), 2.05 (s, 2H), 1.37 (s, 3H), 1.27 (s, 3H); ESI-MS: m / z 548.2 (M+H)+. Example 21: Preparation of (1R,2S)-N1-(4-chlorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4- yl)oxy)-3-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 0.7 g, 2.227 mmol, 1.0 eq) in DCM (30 ml) was added (1S,3R)-3-((4- chlorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 6, 1.78 g, 6.681 mmol, 3.0 eq), EDC.HCl (1.699 g, 8.908 mmol, 4.0 eq) and 4- Dimethylaminopyridine (0.163 g, 1.336 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. The reaction mixture was diluted with water (200 ml) and extracted with DCM (3x200 ml). The combined organic layer was washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient. The fractions containing the expected product were combined and concentrated under reduced pressure. The obtained solid was dissolved in DCM (1 ml), hexane (20 ml) was added and stirred at room temperature for 30 minutes. The solid was filtered and then dried under vacuum to obtain the title compound (0.1 g, yield: 7.96%) as an off-white solid. Chemical purity by HPLC: 98.70%; enantiomeric purity by chiral HPLC: 99.32%;1H NMR (300 MHz, CDCl3): δ ppm 10.46 (s, 1H), 9.30 (s, 1H), 8.48 (d, J = 5.4 Hz, 1H), 7.82 (d, J = 12.3 Hz, 1H), 7.59-7.54 (m, 3H), 7.41-7.18 (m, 5H), 6.42 (d, J = 5.4 Hz, 1H), 4.06 (s, 3H), 4.03 (s, 3H), 2.03 (d, J = 8.4 Hz, 1H), 1.93 (d, J = 8.4 Hz, 1H), 1.42 (s, 3H), 1.38 (s, 3H); ES-MS: m / z 564.16 (M+H)+. Example 21a: Preparation of (1S,2R)-N1-(4-chlorophenyl)-N2-(4-((6,7-dimethoxyquinolin- 4-yl)oxy)-3-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a solution of (1R,3S)-3-((4-chlorophenyl)carbamoyl)-2,2-dimethylcyclopropane- 1-carboxylic acid (Intermediate 6a, 0.511 g, 1.908 mmol, 1.2 eq), in DCM (10 ml) was added DMAP (0.058 g, 0.477 mmol, 0.3 eq) and 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluoroaniline (Intermediate 10, 0.500 g, 1.59 mmol, 1.0 eq). Reaction mass was stirred at room temperature for 10 minutes. Reaction mass was cooled to 0-10 °C, 1-propane phosphonic anhydride solution (T3P) (2.024 ml, 3.181 mmol, 2.0 eq, 50% in EtOAc) was added dropwise, stirred at same temperature for about 1 hour. Cooling bath was removed, and the reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was diluted with DCM (50 ml), cooled to 0-10 °C, pH adjusted to around 8.0 with 10% NaHCO3 solution. Organic layer was separated, and the aqueous layer was extracted with DCM (2x40 ml). The combined organic layer was washed with 7% acetic acid solution (30 ml), 5% sodium bicarbonate solution (30 ml), water (30 ml) and brine solution (20 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0-3% methanol in dichloromethane gradient to obtain the product (0.242 g, yield: 27%) as a solid. ESI-MS: m / z 564.22 (M+H)+. Example 22: Preparation of (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethyl-N2-(5-methylisoxazol-3-yl)cyclopropane-1,2-dicarboxamide: To a stirred solution of (1R,3S)-2,2-dimethyl-3-((5-methylisoxazol-3- yl)carbamoyl)cyclopropane-1-carboxylic acid (Intermediate 7, 0.605 g, 2.546 mmol, 1.0 eq) in DCM (8 ml) was added EDC.HCl (1.4 g, 7.638 mmol, 3.0 eq) and 4-dimethylaminopyridine (0.186 g, 1.527 mmol, 0.6 eq). The reaction mixture was stirred for 10 minutes. 4-((6,7- dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 0.800 g, 2.546 mmol, 1.0 eq) was added and the reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml) and washed with water (100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.035 g, yield: 2.5%) as an off-white solid. Chemical purity by HPLC: 90.59%;1H NMR (300 MHz, DMSO-d6): δ ppm 11.21 (s, 1H), 10.64 (s, 1H), 8.47 (d, J = 3.0 Hz, 1H), 7.87 (d, J = 7.5 Hz, 1H), 7.72-7.66 (m, 1H), 7.52 (s, 1H), 7.42-7.40 (m, 2H), 6.52 (s, 1H), 6.45 (d, J = 3.3 Hz, 1H), 3.95 (s, 6H), 2.37 (s, 3H), 2.02 (d, 1H), 1.90 (d, 1H), 1.29 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 535.26 (M+H)+. Example 23: Preparation of (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethyl-N2-(5-methylisoxazol-3-yl)cyclopropane-1,2-dicarboxamide: To a stirred solution of enantiopure (1S,3R)-2,2-dimethyl-3-((5-methylisoxazol-3- yl)carbamoyl)cyclopropane-1-carboxylic acid (Intermediate 8, 0.605 g, 2.546 mmol, 1.0 eq) in DCM (8 ml) was added EDC.HCl (1.4 g, 7.638 mmol, 3.0 eq) and 4-dimethylaminopyridine (0.186 g, 1.527 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for 10 minutes, then 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 0.800 g, 2.546 mmol, 1.0 eq) was added and stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml) and washed with water (100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in DCM gradient to obtain the title compound (0.200 g, yield: 14.7%) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 9.01 (s, 1H), 8.51 (d, J = 4.5 Hz, 1H), 7.98 (s, 1H), 7.77 (d, J = 11.5 Hz, 1H), 7.59 (s, 1H), 7.52 (s, 1H), 7.22 (t, J = 8.0 Hz, 1H), 6.69 (s, 1H), 6.45 (d, J = 5.0 Hz, 1H), 4.07 (s, 6H), 2.48 (d, J = 5.0 Hz, 1H), 2.42 (s, 3H), 2.39 (d, J = 5.0 Hz, 1H), 1.43 (s, 3H), 1.37 (s, 3H); ES-MS: m / z 535.57 (M+H)+. Example 24: Preparation of (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(3- morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 0.117 g, 0.468 mmol, 2.0 eq) in DCM (10 ml) was added EDC.HCl (0.156 g, 0.819 mmol, 3.5 eq) and 4- dimethylaminopyridine (0.020 g, 0.163 mmol, 0.7 eq). The reaction mixture was stirred at room temperature for 15 minutes, 3-fluoro-4-((6-methoxy-7-(3- morpholinopropoxy)quinolin-4-yl)oxy)aniline (Intermediate 14, 0.100 g, 0.234 mmol, 1.0 eq) was added and the reaction mixture was stirred at room temperature for 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml) and washed with water. The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.030 g, yield: 19.4%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.41 (s, 1H), 10.13 (s, 1H), 8.45 (d, J = 5.5 Hz, 1H), 7.85 (d, 1H), 7.59-7.52 (m, 3H), 7.40-7.39 (m, 3H), 7.11 (t, J = 8.5 Hz, 2H), 6.44 (d, J = 4.5 Hz, 1H), 4.21 (t, J = 6.0 Hz, 2H), 3.94 (s, 3H), 3.63 (m, 4H), 2.57 (m, 4H), 2.41 (m, 2H), 2.05-2.03 (m, 4H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 661.11 (M+H)+. of (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(3- morpholinopropoxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of 3-fluoro-4-((7-methoxy-6-(3-morpholinopropoxy)quinolin- 4-yl)oxy)aniline (Intermediate 15, 0.7 g, 1.637 mmol, 1.0 eq) in DCM (20 ml) was added (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 0.82 g, 3.275 mmol, 2.0 eq), EDC.HCl (0.78 g, 4.09 mmol, 2.5 eq) and 4- dimethylaminopyridine (0.12 g, 0.982 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for 2 days. The reaction mixture was diluted with DCM (30 ml) and washed with water (25 ml). The aqueous layer was back extracted with DCM (25 ml). The combined organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 4% methanol in dichloromethane eluent to afford the title compound (0.060 g) as an off-white solid.1H NMR (500 MHz, CDCl3): δ ppm 10.51 (s, 1H), 8.77 (s, 1H), 8.49 (s, 1H), 7.84 (d, J = 10.5 Hz, 1H), 7.61 (s, 1H), 7.57-7.55 (m, 2H), 7.46 (s, 1H), 7.37 (d, J = 9.0 Hz, 1H), 7.21 (t, J = 8.5 Hz, 1H), 7.07 (t, J = 8.5 Hz, 2H), 6.435 (d, J = 4.5 Hz, 1H), 4.30 (t, J = 6.5 Hz, 2H), 4.04 (s, 3H), 3.78 (t, J = 4.5 Hz, 4H), 2.69 (t, J = 6.5 Hz, 2H), 2.60 (m, 4H), 2.20 (t, J = 7.0 Hz, 2H), 2.07 (d, J = 8.0 Hz, 1H), 1.94 (d, J = 8.5 Hz, 1H), 1.46 (s, 3H), 1.44 (s, 3H); ES-MS: m / z 661.11 (M+H)+. Example 26: Preparation of (1S,2R)-N1-(3-fluoro-4-((7-hydroxy-6-methoxyquinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 0.579 g, 2.305 mmol, 1.5 eq) in DCM (15 ml) was added EDC.HCl (0.736 g, 3.842 mmol, 2.5 eq) and 4- dimethylaminopyridine (0.112 g, 0.922 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for 30 minutes. 4-((7-(benzyloxy)-6-methoxyquinolin-4-yl)oxy)-3- fluoroaniline (Intermediate 16, 0.600 g, 1.536 mmol, 1.0 eq) was added and the reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml) and washed with water (100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.400 g, yield: 41.9%) as an off-white solid.1H NMR (500 MHz, DMSO- d6): δ ppm 10.40 (s, 1H), 10.13 (s, 1H), 8.45 (d, J = 5.0 Hz, 1H), 7.84 (d, J = 13.5 Hz, 1H), 7.72-7.66 (m, 1H), 7.59-7.50 (m, 5H), 7.44-7.35 (m, 5H), 7.13-7.09 (m, 2H), 6.45 (d, J = 5.5 Hz, 1H), 5.31 (s, 2H), 3.95 (s, 3H), 2.05 (s, 2H), 1.37 (s, 3H), 1.27 (s, 2H); ES-MS: m / z 624.34 (M+H)+. Step 2: Synthesis of (1S,2R)-N1-(3-fluoro-4-((7-hydroxy-6-methoxyquinolin-4- To a stirred solution of (1S,2R)-N1-(4-((7-(benzyloxy)-6-methoxyquinolin-4- yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide (Step 1, 0.400 g, 0.641 mmol, 1.0 eq) in DCM (10 ml) at -78 °C was added trichloro borane (1.0 ml). The reaction mixture was stirred at -78 °C for 10 minutes. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was quenched with methanol (10 ml), then Et3N (3 ml) dissolved in Methanol (10 ml) was added dropwise at -78 °C. The reaction mixture was allowed to stir at room temperature for 2 hours. Reaction mixture was evaporated under reduced pressure till methanol was distilled off completely. The residue was dissolved in DCM (200 ml), washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.120 g, yield: 35%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.40 (s, 1H), 10.18 (s, 1H), 10.12 (s, 1H), 8.40 (d, J = 5.0 Hz, 1H), 7.83 (d, J = 12.0 Hz, 1H), 7.58 (dd, J = 9.0, 5.0 Hz, 2H), 7.51 (s, 1H), 7.38 (d, J = 6.0 Hz, 2H), 7.29 (s, 1H), 7.11 (t, J = 9.0 Hz, 2H), 6.385 (d, J = 5.0 Hz, 1H), 3.95 (s, 3H), 2.05 (s, 2H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 534.26 (M+H)+. Example 27: Preparation of tert-butyl 4-((4-(2-fluoro-4-((1S,3R)-3-((4- fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxamido)phenoxy)-6- methoxyquinolin-7-yl)oxy)piperidine-1-carboxylate: To a stirred solution of (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 1.8 g, 7.142 mmol, 1.5 eq) in DCM (23 ml) was added EDC.HCl (2.3 g, 11.904 mmol, 2.5 eq) and 4-dimethylaminopyridine (0.350 g, 2.857 mmol, 0.6 eq). The reaction mixture was stirred at room temperature for 30 minutes. tert-butyl 4-((4-(4-amino-2-fluorophenoxy)-6-methoxyquinolin-7- yl)oxy)piperidine-1-carboxylate (Intermediate 17, 2.3 g, 4.762 mmol, 1.0 eq) was added and stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml) and washed with water (2x100 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.560 g, yield: 16.4%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.41 (s, 1H), 10.12 (s, 1H), 8.495 (d, J = 5.0 Hz, 1H), 7.84 (d, J = 13.0 Hz, 1H), 7.59- 7.53 (m, 4H), 7.395 (d, J = 4.5 Hz, 2H), 7.11 (t, J = 9.0 Hz, 2H), 6.50 (d, J = 4.5 Hz, 1H), 4.84-4.80 (m, 1H), 3.95 (s, 3H), 3.74-3.71 (m, 2H), 3.23 (m, 2H), 2.09 (s, 2H), 2.05-2.01 (m, 2H), 1.61 (t, J = 4.5 Hz, 2H), 1.42 (s, 9H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 717.56 (M+H)+. Example 28: Preparation of (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(piperidin-4- yloxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide 2,2,2-trifluoroacetate: To a stirred solution of tert-butyl 4-((4-(2-fluoro-4-((1S,3R)-3-((4- fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1-carboxamido)phenoxy)-6- methoxyquinolin-7-yl)oxy)piperidine-1-carboxylate (Example 27, 0.500 g, 0.698 mmol, 1.0 eq) in DCM (8 ml) at room temperature was added trifluoro acetic acid (2 ml). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The reaction mixture was cooled to 0 °C, basified with saturated sodium bicarbonate solution and extracted with DCM (3x200 ml). The combined organic layer was washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was treated with 10% DCM:Hexane, the obtained solid was filtered, washed with hexane and dried under vacuum to obtain the desired compound (0.300 g, yield: 69.7%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.40 (s, 1H), 10.12 (s, 1H), 8.44 (d, J = 5.0 Hz, 1H), 7.83 (d, J = 14.0 Hz, 1H), 7.58 (dd, J = 9.0, 5.0 Hz, 2H), 7.52 (s, 1H), 7.46 (s, 1H), 7.38-7.35 (m, 2H), 7.11 (t, J = 9.0 Hz, 2H), 6.43 (d, J = 5.0 Hz, 1H), 4.69-4.66 (m, 1H), 3.94 (s, 3H), 3.04-3.01 (m, 2H), 2.70 (t, J = 10.0 Hz, 2H), 2.05- 2.03 (m, 4H), 1.61-1.54 (m, 2H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 617.4 (M+H)+. Example 29: Preparation of (1S,2R)-N1-(4-((7-((1-acryloylpiperidin-4-yl)oxy)-6- methoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(piperidin-4- yloxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide 2,2,2-trifluoroacetate (Example 28, 0.250 g, 0.405 mmol, 1.0 eq) in DCM (20 ml) was added triethylamine (0.13 ml, 1.217 mmol, 3.0 eq) and acryloyl chloride (0.05 ml, 0.608 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (100 ml) and washed with water. The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to obtain the title compound (0.050 g, yield: 18%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.41 (s, 1H), 10.12 (s, 1H), 8.49 (s, 1H), 7.84 (d, J = 13.0 Hz, 1H), 7.70-7.68 (m, 1H), 7.59-7.55 (m, 3H), 7.395 (d, J = 4.0 Hz, 2H), 7.11 (t, J = 9.0 Hz, 2H), 6.84 (dd, J = 17.0, 10.5 Hz, 1H), 6.50 (s, 1H), 6.12 (dd, J = 16.5, 2.5 Hz, 1H), 5.68 (dd, J = 10.5, 2.5 Hz, 1H), 4.90 (m, 1H), 3.95 (s, 3H), 3.40-3.20 (m, 4H), 2.05 (m, 4H), 1.68-1.64 (m, 2H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 671.5 (M+H)+. Example 30: Preparation of 4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6,7-dimethoxyquinoline 1-oxide: To a stirred solution of (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide (Example 15, 2.5 g, 4.565 mmol, 1.0 eq) in DCM (25 ml) was added meta-Chloroperbenzoic acid (2.3 g, 13.697 mmol, 3.0 eq). The reaction mixture was stirred at room temperature for 2.5 hours. The reaction mixture was cooled to 0 °C, quenched with saturated sodium sulphite (25 ml) solution. Organic layer was separated, and aqueous layer was extracted with DCM (2x75 ml). The combined organic layer was washed with water (75 ml) and brine solution (50 ml). The organic layer was dried with sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0- 10% methanol in dichloromethane gradient. The fractions containing the expected product were combined and concentrated under reduced pressure. The obtained compound was stirred with heptane (50 ml) at room temperature for 1 hour. Solid was filtered and dried under vacuum at 50-60 °C for 2 hours to obtain the desired compound (1.6 g) as a pale violet colour solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.4 (s, 1H), 10.12 (s, 1H), 8.24 (d, J = 6.5 Hz, 1H), 7.92 (s, 1H), 7.83 (d, J = 13.5 Hz, 1H), 7.59-7.54 (m, 3H), 7.40-7.37 (m, 2H), 7.11 (t, J = 8.5 Hz, 2H), 6.47 (d, J = 7.0 Hz, 1H), 3.99 (s, 3H), 3.97 (s, 3H), 2.04 (s, 2H), 1.36 (s, 3H), 1.26 (s, 3H); ES-MS: m / z 564.38 (M+H)+. Example 31: Preparation of (1R,2S)-N1-(3,4-difluorophenyl)-N2-(4-((6,7- dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide: To a stirred solution of (1S,3R)-3-((3,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 4, 0.514 g, 1.908 mmol, 1.2 eq) in DCM (10 ml) was added 4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 0.500 g, 1.590 mmol, 1.0 eq) followed by EDC.HCl (2.133 g, 11.13 mmol, 7.0 eq) and 4- dimethylaminopyridine (0.116 g, 0.954 mmol, 0.6 eq). The reaction mass was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. The reaction mass was diluted with DCM (50 ml) and washed with water (2x40 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-5% methanol in dichloromethane gradient to obtain the title compound (0.170 g) as an off- white solid. Chemical purity by HPLC: 95.69%;1H NMR: (500 MHz, DMSO-d6): δ ppm 10.37 (s, 1H), 10.26 (s, 1H), 8.46 (d, J = 5.0 Hz, 1H), 7.83-7.81 (m, 1H), 7.77-7.73 (m, 1H), 7.52 (s, 1H), 7.40-7.24 (m, 5H), 6.44 (d, J = 5.0 Hz, 1H), 3.94 (s, 6H), 2.07 (d, J = 9.5 Hz, 1H), 2.05 (d, J = 9.0 Hz, 1H), 1.37 (s, 3H), 1.27 (s, 3H). Example 31a: Preparation of (1S,2R)-N1-(3,4-difluorophenyl)-N2-(4-((6,7- dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide: To a solution of (1R,3S)-3-((3,4-difluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 4a, 0.514 g, 1.908 mmol, 1.2 eq) in DCM (10 ml) was added DMAP (0.058 g, 0.477 mmol, 0.3 eq) and 4-((6,7- dimethoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 10, 0.500 g, 1.59 mmol, 1.0 eq). Reaction mass was stirred at room temperature for 10 minutes. Reaction mass was cooled to 0-10 °C, 1-propane phosphonic anhydride solution (T3P) (2.024 ml, 3.181 mmol, 2.0 eq, 50% in EtOAc) was added dropwise, stirred at same temperature for about 1 hour. Cooling bath was removed, and the reaction mass was stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was diluted with DCM (50 ml), cooled to 0-10 °C, pH adjusted to around 8.0 with 10% NaHCO3 solution. Organic layer was separated, and the aqueous layer was extracted with DCM (2x40 ml). The combined organic layer was washed with 7% acetic acid solution (20 ml), 5% sodium bicarbonate solution (30 ml), water (50 ml) and brine solution (20 ml). Organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. Crude compound was purified by column chromatography using 0-5% methanol in dichloromethane gradient to obtain the product (0.305 g, 34% yield) as a solid. ESI-MS: m / z 588.21 (M+Na)+. Example 32: Preparation of -N1-(3-fluoro-4-((6-hydroxy-7-methoxyquinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide: To a stirred solution of (1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxylic acid (Intermediate 3, 0.482 g, 1.921 mmol, 1.5 eq) in DCM (10 ml) was added 4-dimethylaminopyridine (0.078 g, 0.640 mmol, 0.5 eq), 4-((6- (benzyloxy)-7-methoxyquinolin-4-yl)oxy)-3-fluoroaniline (Intermediate 18, 0.500 g, 1.280 mmol, 1.0 eq) and EDC.HCl (1.7 g, 8.96 mmol, 7.0 eq). The reaction mas was stirred at room temperature for overnight. TLC indicated starting material was completed and the desired product was observed. The reaction mass was diluted with DCM (200 ml) and washed with water (200 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the product (0.300 g, yield: 37.59%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.4 (s, 1H), 10.12 (s, 1H), 8.47 (d, J = 5.5 Hz, 1H), 7.84 (d, J = 12.0 Hz, 1H), 7.72-7.66 (m, 2H), 7.58 (dd, J = 9.0, 5.5 Hz, 2H), 7.52 (d, J = 7.0 Hz, 2H), 7.43-7.40 (m, 3H), 7.38-7.34 (m, 2H), 7.11 (t, J = 9.0 Hz, 2H), 6.45 (d, J = 5.0 Hz, 1H), 5.27 (s, 2H), 3.95 (s, 3H), 2.05 (s, 2H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 624.34 (M+H)+. Step 2: Synthesis of (1S,2R)-N1-(3-fluoro-4-((6-hydroxy-7-methoxyquinolin-4- Method 1: To a stirred solution of (1S,2R)-N1-(4-((6-(benzyloxy)-7-methoxyquinolin-4- yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide (Step 1, 0.300 g, 0.481 mmol, 1.0 eq) in DCM (10 ml) at -78 °C was added BCl3 (2.88 ml, 2.8861 mmol, 6.0 eq 1.0 M in DCM) dropwise at -78 °C. The reaction mass was stirred at - 78 °C for 1 hour. TLC indicated starting material was completed and the desired product was observed. The reaction mass quenched at -78 °C by adding methanol (10 ml) followed by triethylamine (3 ml) mixed in methanol (10 ml). Cooling bath was removed and the reaction mass allowed to stir at room temperature for 1 hour. Reaction mass was evaporated under reduced pressure. The residue was dissolved in DCM (200 ml), washed with water (200 ml), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the product (0.110 g, yield: 43%) as an off-white solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.41 (s, 1H), 10.13 (s, 1H), 8.44 (d, J = 5.5 Hz, 1H), 7.83 (d, J = 12.0 Hz, 1H), 7.59-7.56 (m, 2H), 7.50 (s, 1H), 7.39-7.36 (m, 3H), 7.13-7.09 (m, 2H), 6.47 (d, J = 5.0 Hz, 1H), 3.96 (s, 3H), 2.05 (s, 2H), 1.37 (s, 3H), 1.27 (s, 3H); ES-MS: m / z 534.23 (M+H)+. Method 2: To a stirred solution of (1S,2R)-N1-(4-((6-(benzyloxy)-7-methoxyquinolin-4-yl)oxy)- 3-fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide (Step 1, 10 g, 16.03 mmol, 1.0 eq) in Trifluoroacetic acid (50 ml) was added methane sulfonic acid (3.08 g, 32.06 mmol, 2.0 eq). Reaction mass was stirred at room temperature for about 7 hours. TLC indicated starting material was consumed and the desired product was observed. Reaction mass was evaporated under reduced pressure, pH adjusted to 7.0 with 1N NaOH solution. The resulting solid was filtered, washed with water (100 ml) and then dried under vacuum. Crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (7.61 g, yield: 89%) as an off-white solid. Example 33: Preparation of (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(2,2,2- trifluoroethoxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane- 1,2-dicarboxamide: To a stirred solution of (1S,2R)-N1-(3-fluoro-4-((6-hydroxy-7-methoxyquinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide (Example 32, 0.200 g, 0.374 mmol, 1.0 eq) in N-methyl pyrrolidone (2 ml) at 0 °C was added potassium carbonate (0.103 g, 0.748 mmol, 2.0 eq) and 1,1,1-trifluoro-2-iodoethane (0.314 g, 0.148 ml, 1.495 mmol, 4.0 eq). The reaction mass was allowed to stir at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. Water (40 ml) was added to the reaction mass and extracted with ethyl acetate (50 ml). The combined organic layer was washed with water (20 ml) and brine solution (20 ml). The organic layer was dried over sodium sulphate, filtered and evaporated under reduced pressure. The crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the product (0.040 g, yield: 17.4%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.40 (s, 1H), 10.12 (s, 1H), 8.51 (d, J = 5.5 Hz, 1H), 7.84 (dd, 1H), 7.74 (s, 1H), 7.60-7.56 (m, 2H), 7.47 (s, 1H), 7.39-7.35 (m, 2H), 7.11 (t, J = 8.5 Hz, 2H), 6.47 (d, J = 5.0 Hz, 1H), 4.98 (dd, J = 17.5, 9.0 Hz, 2H), 3.98 (s, 3H), 2.05 (s, 2H), 1.37 (s, 3H), 1.35 (s, 3H). Example 34: Preparation of tert-butyl 4-((4-(2-fluoro-4-((1S,3R)-3-((4- To a solution of (1S,2R)-N1-(3-fluoro-4-((6-hydroxy-7-methoxyquinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide (Example 32, 0.600 g, 1.124 mmol, 1.0 eq) in 1-methylpyrrolidin-2-one (12 ml) at 0 °C was added potassium carbonate (0.466 g, 3.372 mmol, 3.0 eq). The reaction mixture was stirred at room temperature for 30 minutes. tert-butyl 4-((methylsulfonyl)oxy)piperidine-1- carboxylate (Intermediate 17-step 2, 0.628 g, 2.245 mmol, 2.0 eq) and potassium iodide (0.018 g, 0.112 mmoles, 0.1 eq) were added to the reaction mass and heated at 95-105 °C for 6 hours. TLC indicated starting material was not completed, again, tert-butyl 4- ((methylsulfonyl)oxy)piperidine-1-carboxylate (Intermediate 17-step 2) (0.628 g, 2.245 mmol, 2.0 eq) was added and reaction mass heated at 95-105 °C for 2 hours. TLC indicated starting material was completed and the desired product was observed. Water (120 ml) was added to the reaction mass, stirred at room temperature for 1 hour. Solid was filtered, washed with water (50 ml) and then dried under vacuum. The crude compound was purified by silica gel column chromatography using 0-4% methanol in dichloromethane gradient to obtain the product (0.500 g, yield: 62%) as a solid.1H NMR (500 MHz, DMSO-d6): δ ppm 10.39 (s, 1H), 10.12 (s, 1H), 8.46 (d, J = 5.5 Hz, 1H), 7.83 (d, J = 12.5 Hz, 1H), 7.63 (s, 1H), 7.59-7.56 (m, 2H), 7.42 (s, 1H), 7.38-7.35 (m, 2H), 7.11 (t, J = 8.5 Hz, 2H), 6.44 (d, J = 5.0 Hz, 1H), 4.80-4.77 (m, 1H), 3.94 (s, 3H), 3....

Claims

1. 32 A A A A A ND 33 B C C A B ND 36 A A A A A ND 44 A A A A A B 47 A A A A A B 55 A A A A A A 56 A A A A A A 58 A A A A A B 60 A A A A A A *ND- Not Determined Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as described above. All publications and patent applications cited in this application are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated herein by reference.We Claim, 1. A compound of Formula (I):Formula (I) wherein, ‘X’ is selected from -O- or -S-; R1 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; or R1 and R2 together with the oxygen atoms to which they are attached to form a 6-12 membered heterocyclic ring; ringaryl or heteroaryl; R3 is selected from hydrogen, hydroxyl, halo, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro, or amino; R4 and R5 are independently selected from hydrogen or C1-C6 alkyl or R4 and R5 are taken together with the carbon atom(s) to which they are attached to form substituted or unsubstituted C3-C10 cycloalkyl; wherein one or more substituents are independently selected from halogen or C1-C6 alkyl;R6 is selected form hydrogen, amino, hydroxyl, -O-Rb, halo, C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted aryl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro, -C(O)-alkyl, -C(O)-O-alkyl or amino; wherein the substituents are independently selected from one or more amino, cyano, halo, C1-C6 haloalkyl, hydroxy, C1-C6 alkyl or C1- C6 alkoxy; R7 is hydrogen or C1-C6 alkyl; R8 is hydrogen or C1-C6 alkyl; ring is selected from C3-C6 cycloalkyl, C6-C12 aryl, C6-C12 arylalkyl, heteroaryl, or heterocyclyl; Ra is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; Rbis selected from hydrogen, C1-C6alkyl, C1-C6alkenyl or C1-C6haloalkyl; optional bond; ‘m’ is an integer selected from 0, 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, 2, 3, 4 or 5; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides, or combination thereof.

2. The compound according to claim 1, wherein the compound of Formula (I) is a compound of the Formula (IA):Formula (IA) R1 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra;R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; or R1 and R2 together with the oxygen atoms to which they are attached to form a 6-12 membered heterocyclic ring; ring is C6-C12 aryl or heteroaryl; R3 is selected from hydrogen, hydroxyl, halo, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6alkoxy, cycloalkyloxy, cyano, nitro or amino; R4 and R5 are independently selected from hydrogen or C1-C6 alkyl, or R4 and R5 are taken together with the carbon atom(s) to which they are attached to form substituted or unsubstituted C3-C10 cycloalkyl; wherein one or more substituents are independently selected from halogen or C1-C6 alkyl; R6 is selected form hydrogen, amino, hydroxyl, -O-Rb, halo, C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted aryl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro, -C(O)-alkyl, -C(O)-O-alkyl or amino; wherein the substituents are independently selected from one or more amino, cyano, halo, C1-C6 haloalkyl, hydroxy, C1-C6 alkyl or C1- C6 alkoxy; R7is hydrogen or C1-C6alkyl; R8 is hydrogen or C1-C6 alkyl; ring is selected from C3-C6 cycloalkyl, C6-C12 aryl, C6-C12 arylalkyl, heteroaryl, or heterocyclyl; Ra is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; Rb is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; ‘---’ is an optional bond; ‘m’ is an integer selected from 0, 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, 2, 3, 4 or 5; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or combination thereof.

3. The compound according to claim 1, wherein the compound of Formula (I) is a compound of Formula (IB):Formula (IB) R1 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; or R1 and R2 together with the oxygen atoms to which they are attached to form a 6-12 membered heterocyclic ring; R3 is selected from hydrogen, hydroxyl, halo, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro or amino; R4 and R5 are independently selected from hydrogen or C1-C6 alkyl or R4 and R5 are taken together with the carbon atom(s) to which they are attached to form substituted or unsubstituted C3-C10 cycloalkyl; wherein one or more substituents are independently selected from halogen or C1-C6 alkyl; R6is selected form hydrogen, amino, hydroxyl, -O-Rb, halo, C1-C6alkyl, C3-C6cycloalkyl, substituted or unsubstituted aryl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro, -C(O)-alkyl, -C(O)-O-alkyl or amino; wherein the substituents are independentlyselected from one or more amino, cyano, halo, C1-C6 haloalkyl, hydroxy, C1-C6 alkyl or C1- C6 alkoxy; R7 is hydrogen or C1-C6 alkyl; R8 is hydrogen or C1-C6 alkyl; ring is selected from C3-C6 cycloalkyl, C6-C12 aryl, C6-C12 arylalkyl, heteroaryl, or heterocyclyl; Ra is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; Rb is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; ‘---’ is an optional bond; ‘m’ is an integer selected from 0, 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, 2, 3, 4 or 5; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or combination thereof.

4. The compound according to claim 1, wherein the compound of Formula (I) is a compound of Formula (IC):Formula (IC) R1 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted orunsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra; or R1 and R2 together with the oxygen atoms to which they are attached to form a 6-12 membered heterocyclic ring; R3 is selected from hydrogen, hydroxyl, halo, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro or amino; R4 and R5 are independently selected from hydrogen or C1-C6 alkyl or R4 and R5 are taken together with the carbon atom(s) to which they are attached to form substituted or unsubstituted C3-C10 cycloalkyl; wherein one or more substituents are independently selected from halogen or C1-C6 alkyl; R6 is selected form hydrogen, amino, hydroxyl, -O-Rb, halo, C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted aryl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro, -C(O)-alkyl, -C(O)-O-alkyl or amino; wherein the substituents are independently selected from one or more amino, cyano, halo, C1-C6 haloalkyl, hydroxy, C1-C6 alkyl or C1- C6 alkoxy; R7 is hydrogen or C1-C6 alkyl; R8 is hydrogen or C1-C6 alkyl; Ra is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; Rb is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; ‘---’ is an optional bond; ‘m’ is an integer selected from 0, 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, 2, 3, 4 or 5; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or combination thereof.

5. The compound according to claim 1, wherein the compound of Formula (I) is a compound of Formula (ID):Formula (ID)R1 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, - C(O)-O-Ra or -N(H)-C(O)-O-Ra;R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are independently selected from one or more C1-C6 alkyl, halo, hydroxy, cyano, amino, nitro, alkoxy, heterocyclyl, -C(O)-Ra, -C(O)-O-Ra or -N(H)-C(O)-O-Ra; or R1 and R2 together with the oxygen atoms to which they are attached to form a 6-12 membered heterocyclic ring; R3 is selected from hydrogen, hydroxyl, halo, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro or amino; R6 is selected form hydrogen, amino, hydroxyl, -O-Rb, halo, C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted aryl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro, -C(O)-alkyl, -C(O)-O-alkyl or amino; wherein the substituents are independentlyselected from one or more amino, cyano, halo, C1-C6 haloalkyl, hydroxy, C1-C6 alkyl or C1-C6 alkoxy; Ra is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; Rb is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; ‘m’ is an integer selected from 0, 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, 2, 3, 4 or 5; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or combination thereof.

6. The compound according to claim 1, wherein the compound of Formula (I) is a compound of Formula (IE):Formula (IE) R3 is selected from hydrogen, hydroxyl, halo, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro or amino; R6 is selected form hydrogen, amino, hydroxyl, -O-Rb, halo, C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted aryl, C1-C6 haloalkyl, C1-C6 alkoxy, cycloalkyloxy, cyano, nitro, -C(O)-alkyl, -C(O)-O-alkyl or amino; wherein the substituents are independently selected from one or more amino, cyano, halo, C1-C6 haloalkyl, hydroxy, C1-C6 alkyl or C1- C6 alkoxy; Rb is selected from hydrogen, C1-C6 alkyl, C1-C6 alkenyl or C1-C6 haloalkyl; ‘m’ is an integer selected from 0, 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, 2, 3, 4 or 5; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or combination thereof.

7. The compound according to claim 1, wherein the compound of Formula (I) is selected from: N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)fumaramide; N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)maleamide; N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N4-(4- fluorophenyl)succinimide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclobutane-1,2-dicarboxamide;(1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclobutane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopentane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclopentane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclohexane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)cyclohexane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl-3,3- dimethylcyclopropane-1,2-dicarboxamid; (1R,2S)-N1-(3-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-cyclopropyl-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-methylphenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-methylphenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide;(1R,2S)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2- methylphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2- methylphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(2-chloro-4-((6,7-dimethoxyquinolin-4-yl)oxy)phenyl)-N2-cyclopropyl-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-chlorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-chlorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2-(5- methylisoxazol-3-yl)cyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2-(5- methylisoxazol-3-yl)cyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(3-morpholinopropoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(3-morpholinopropoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-hydroxy-6-methoxyquinolin-4-yl)oxy)phenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; 4-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxamido)phenoxy)-6-methoxyquinolin-7-yl)oxy)piperidine-1-carboxylate; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(piperidin-4-yloxy)quinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetate; (1S,2R)-N1-(4-((7-((1-acryloylpiperidin-4-yl)oxy)-6-methoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; 4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxamido)phenoxy)-6,7-dimethoxyquinoline 1-oxide; (1R,2S)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide;(1S,2R)-N1-(3,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-hydroxy-7-methoxyquinolin-4-yl)oxy)phenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(2,2,2-trifluoroethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; tert-butyl 4-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6-yl)oxy)piperidine-1- carboxylate; (1S,2R)-N1-(4-((6,7-dihydroxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(piperidin-4-yloxy)quinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetate; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-((1-(2,2,2-trifluoroacetyl)piperidin-4- yl)oxy)quinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(2-methoxyethoxy)quinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(2,2,2-trifluoroethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; tert-butyl (2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6-yl)oxy)ethyl)carbamate; (1S,2R)-N1-(4-((6,7-bis(2-methoxyethoxy)quinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(2-methoxyethoxy)quinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6-(2-aminoethoxy)-7-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2- (4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid; (1S,2R)-N1-(4-((7-(3-aminopropoxy)-6-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid; tert-butyl (3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)carbamate;tert-butyl (3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)carbamate; (1S,2R)-N1-(4-((6-(3-aminopropoxy)-7-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid; (1S,2R)-N1-(4-((6,7-bis(3-methoxypropoxy)quinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(3-methoxypropoxy)quinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(3-methoxypropoxy)quinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; tert-butyl (2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7-yl)oxy)ethyl)carbamate; (1S,2R)-N1-(4-((7-(2-aminoethoxy)-6-methoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2- (4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2-trifluoroacetic acid; tert-butyl 4-(3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)propyl)piperazine-1-carboxylate; tert-butyl 4-(2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6-yl)oxy)ethyl)piperazine- 1-carboxylate; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(2-(piperazin-1-yl)ethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(3-(piperazin-1-yl)propoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid; tert-butyl 4-(2-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7-yl)oxy)ethyl)piperazine- 1-carboxylate; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(2-(piperazin-1-yl)ethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid;tert-butyl 4-(3-((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)propyl)piperazine-1-carboxylate; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(3-(piperazin-1-yl)propoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid; 4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2-dimethylcyclopropane-1- carboxamido)phenoxy)-6-hydroxy-7-methoxyquinoline 1-oxide; (1S,2R)-N1-(3-fluoro-4-((6-(3-hydroxypropoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-(2-hydroxyethoxy)-7-methoxyquinolin-4-yl)oxy)phenyl)- N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(6-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-3-yl)-N2-(4-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(((S)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(6-((6,7-dimethoxyquinolin-4-yl)oxy)-5-fluoropyridin-3-yl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; tert-butyl 4-(((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-6-methoxyquinolin-7- yl)oxy)methyl)piperidine-1-carboxylate; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(piperidin-4-ylmethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)thio)phenyl)-N2-(4-fluorophenyl)-3,3- dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-N2,3,3-trimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-N2,3,3-trimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2-(2- methylbenzo[d]thiazol-6-yl)cyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2-(2- methylbenzo[d]thiazol-6-yl)cyclopropane-1,2-dicarboxamide;(1R,2S)-N1-(2,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(2,4-difluorophenyl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4-fluorobenzyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorobenzyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- methoxyphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- methoxyphenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-9-yl)oxy)-3-fluorophenyl)-N2- (4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(5-((6,7-dimethoxyquinolin-4-yl)oxy)pyridin-2-yl)-N2-(4-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2-(5- methylthiazol-2-yl)cyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2-(5- methylthiazol-2-yl)cyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-(((3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl)oxy)-7- methoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide; tert-butyl 4-(((4-(2-fluoro-4-((1S,3R)-3-((4-fluorophenyl)carbamoyl)-2,2- dimethylcyclopropane-1-carboxamido)phenoxy)-7-methoxyquinolin-6- yl)oxy)methyl)piperidine-1-carboxylate; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(((S)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(benzo[d]thiazol-2-yl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide;(1S,2R)-N1-(benzo[d]thiazol-2-yl)-N2-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- phenylcyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- phenylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-(((3S,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl)oxy)-6- methoxyquinolin-4-yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2- dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-((tetrahydro-2H-pyran-4-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-((tetrahydro-2H-pyran-4-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(piperidin-4-ylmethoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide 2,2,2- trifluoroacetic acid; (1S,2R)-N1-(4-((6-(2-(tert-butoxy)ethoxy)-7-methoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(2-((6,7-dimethoxyquinolin-4-yl)oxy)pyrimidin-5-yl)-N2-(4-fluorophenyl)- 3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((7-(2-(tert-butoxy)ethoxy)-6-methoxyquinolin-4-yl)oxy)-3- fluorophenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-((3-methyloxetan-3-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-((3-methyloxetan-3-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(((R)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(((R)-tetrahydrofuran-3-yl)oxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((7-methoxy-6-(((S)-oxetan-2-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(3-fluoro-4-((6-methoxy-7-(((S)-oxetan-2-yl)methoxy)quinolin-4- yl)oxy)phenyl)-N2-(4-fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide;(1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (quinoxalin-6-yl)cyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (quinoxalin-6-yl)cyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (quinolin-3-yl)cyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (quinolin-3-yl)cyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (pyridin-3-yl)cyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (pyridin-3-yl)cyclopropane-1,2-dicarboxamide; (1S,2R)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (naphthalen-1-yl)cyclopropane-1,2-dicarboxamide; (1R,2S)-N1-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-3-fluorophenyl)-3,3-dimethyl-N2- (naphthalen-1-yl)cyclopropane-1,2-dicarboxamide; and (1S,2R)-N1-(4-((6,7-bis(methoxy-d3)quinolin-4-yl)oxy)-3-fluorophenyl)-N2-(4- fluorophenyl)-3,3-dimethylcyclopropane-1,2-dicarboxamide, or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or combination thereof.

8. A pharmaceutical composition comprising a compound according to any one of claims 1-7 and at least one pharmaceutically acceptable excipient.

9. The pharmaceutical composition according to claim 8, wherein the pharmaceutically acceptable excipient is a carrier or a diluent.

10. A method of modulating the activity of a kinase, the method comprising administering to a subject an effective amount of a compound of Formula (I) according to any one of claims 1-7 or a pharmaceutical composition thereof.

11. The method according to claim 10, wherein the modulating the activity of the kinase comprises inhibition of said kinase.

12. The method according to claim 11, wherein said kinase is at least one of KDR, c-Met, RET, AXL, TEK (Tie 2), PDGFR and EGFR.

13. A method of treating diseases or disorders associated with abnormal, uncontrolled, and / or unwanted activities of kinases, the method comprising administering, to a mammal inneed thereof, a therapeutically effective amount of a compound of Formula (I) according to any one of claims 1-7 or a pharmaceutical composition thereof.

14. The method according to claim 13, wherein said kinase is at least one of KDR, c-Met, RET, AXL, TEK (Tie 2), PDGFR and EGFR.

15. A method of treating cancer, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of Formula (I) according to any one of claims 1-7 or a pharmaceutical composition thereof.

16. The method of claim 15, wherein the cancer is ovarian cancer, prostate cancer, endometrial cancer, renal cancer, hepatocellular carcinoma, thyroid cancer, pancreatic cancer, breast cancer, colorectal carcinoma, oral squamous cell carcinoma and / or lung adenocarcinoma.

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