Benzimidazole compounds as EGFR inhibitors

Abstract

The present invention relates to benzimidazole compounds or pharmaceutically acceptable salts thereof which are useful for the treatment of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (Exon19 deletion, L858R and the Del 19 / T790M and L858R / T790M resistance mutation). The compounds of the present invention and salts thereof are useful in the treatment or prevention of different types of cancers. The present invention also relates to methods of preparation for benzimidazole compounds and pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof; a pharmaceutical composition containing the compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and / or solvates thereof particularly useful polymorphs of the compounds and salts thereof. The present invention also relates to use of the compounds and pharmaceutically acceptable salts, prodrugs, stereoisomers, and solvates thereof in the preparation of a medicament for treating diseases associated with various forms of EGFR. The definitions of X, R1, R2, R3, R4, R5, 'm' and 'n' are as defined herein (Formula I).

Description

[0001] BENZIMIDAZOLE COMPOUNDS AS EGFR INHIBITORS This application claims the benefit of Indian provisional application no. 202441050374 filed on 01stJuly 2024 which is hereby incorporated by reference in its entirety. FIELD OF THE INVENTION The present invention relates to benzimidazole compounds or pharmaceutically acceptable salts thereof which are useful for the treatment of a disease or medical condition mediated through certain mutated forms of epidermal growth factor receptor (Exon19 deletion, L858R and the Del 19 / T790M and L858R / T790M resistance mutation). The present invention also relates to methods of preparation for benzimidazole compounds and pharmaceutically acceptable salts, stereoisomers, prodrugs and solvates thereof; a pharmaceutical composition containing the compounds, pharmaceutically acceptable salts, stereoisomers, prodrugs and / or solvates thereof particularly useful polymorphs of the compounds and salts thereof. The invention also relates to use of the compounds and pharmaceutically acceptable salts, prodrugs, stereoisomers, and solvates thereof in the preparation of a medicament for treating diseases associated with various forms of EGFR. BACKGROUND OF THE INVENTION Lung cancer is the leading cause of cancer-related mortality amongst both men and women, accounting for approximately 25% of all cancer deaths globally. There are two main forms of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which account for 85% and 15% of diagnoses. There are many studies showings that the activation of more than half of the original cancer gene and oncogene are associated with protein tyrosine kinase, and protein tyrosine kinase abnormal expression can lead to disorders of cell proliferation regulation, thereby leading to tumor genesis. Tyrosine kinase has become a very important target for the development of antitumor drugs. Epidermal growth factor receptor (EGFR) is a receptor tyrosine protein kinase, and a transmembrane protein in the ErbB receptor family. It is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: EGFR (ErbB-1 or HER1), HER2 / neu (ErbB-2), Her 3 (ErbB-3) and Her 4 (ErbB-4). 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. In many cancer types, mutations affecting EGFR expression or activity could result in cancer (The Journal of Clinical Investigation.117 (8): 2051–8). Dysregulation of the EGFR leads to increased intracellular pathways activity, via tyrosine kinase autophosphorylation, resulting in directly or indirectly, cell proliferation, angiogenesis, invasion and metastasis (Curr Opin Oncol 2004;16:130-5). Overexpression of the EGFR gene has been identified in a variety other cancer including: head and neck, ovary, cervix, bladder, oesophagus, stomach, brain, breast, endometrium, colon and lung. EGFR overexpression has been identified in between 40% to 89% of NSCLC, with highest rates seen in squamous tumours (89%) and lowest in adenocarcinomas (41%) (Transl Lung Cancer Res.2015 Apr; 4(2): 110–118). The “classical” EGFR mutations consist of a deletion in exon 19 and a single amino acid substitution L858R in exon 21 and account for 47% and 41% of the EGFR mutations in NSCLC, respectively. Erlotinib, Gefitinib, and Icotinib arefirst-generation EGFR TKIs with a reversible mechanism of action, while afatinib is a second-generation of EGFR TKI with an irreversible mechanism of action. However, these second-generation EGFR mutant inhibitors also have a strong inhibitory effect on wild-type EGFR (WT-EGFR). Clinical studies have shown that the inhibition of wild-type EGFR can lead to drug toxicity and side effects in most patients, such as rash or diarrhea in the human body. However, almost all NSCLC patients who undergo treatment with first or second-generation EGFR TKIs eventually experience disease progression due to acquired resistance within two years of treatment. The gatekeeper T790M mutation is the most frequent mutation observed in acquired EGFR TKIs resistance. One strategy to overcome resistance is to develop next-generation EGFR TKIs. Osimertinib, a third-generation EGFR TKI, has been approved for NSCLC patients harboring EGFR exon19 deletions (EGFR[d746–750]), L858R mutation (EGFR [L858R]), or Del 19 / T790M and L858R / T790M mutation (EGFR [T790M] (Biomedicine & Pharmacotherapy Volume 167, November 2023, 115491). Osimertinib was effective as a rescue medication after failing first-generation TKIs, with a median PFS of 10.1 months compared to 4.4 months on platinum-based chemotherapy, and as a first-line therapy with a median PFS of 18.9 months compared to 10.2 months for first-generation TKIs (Cells 2021, 10(5), 1206;). The third-generation EGFR inhibitor, Osimertinib, has a beneficial clinical effect, but its major metabolite, AZ5104, has a strong inhibitory effect on wild-type EGFR (WT-EGFR), which is the most probable incentive inducing the most common side effects such as a clinically common rash, diarrhea and the like. US 8946235 discloses indole compounds as EGFR inhibitors; US 10179784 describes pyrimidine or pyridine compounds as EGFR inhibitors; US1025982 B2 discloses N- substituted indole compounds as EGFR inhibitors; US10072002 B2 discloses pyridinyl amino pyrimidine derivatives as EGFR inhibitors; US9593098 B2 discloses compounds and compositions for modulating EGFR mutant kinase activities. However, currently the EGFR-TKI is still unable to solve the clinical stress caused by drug resistance, and most of the existing drugs are EGFR reversible or irreversible inhibitor in which the basic nucleus is quinazoline or quinoline amine, and the toxic side effects caused by the poor selectivity for wild-type cells are also unavoidable. Therefore, there is an urgent need to provide new types of compounds, particularly novel skeletons, to solve problems such as drug resistance, poor selectivity, and poor pharmacological properties and there is need for the development of new type of compounds which are more potent towards resistance mutations like EGFR exon19 deletions (EGFR[d746–750]), L858R mutation (EGFR [L858R]), or Del 19 / T790M and L858R / T790M and less inhibitory activity against WT EGFR and development of these type of compounds may have better properties like brain penetration, overall responding rates and progression free survival rates. SUMMARY OF THE INVENTION The compounds of the present invention relate to certain benzimidazole compounds and pharmaceutically acceptable salt thereof; and can be used for the treatment or prevention of the disease or condition mediated by some mutated forms of epidermal growth factor receptors (e.g., L858R activated mutants, Exon19 deletion activated mutants, and Del 19 / T790M and L858R / T790M resistant mutants). The compounds of the present invention may exhibit better Physico-chemical properties like higher permeability, higher aqueous solubility and lower plasma protein binding and less toxicity profile or better metabolic profiles. Therefore, the compounds of the present invention may be especially useful in the treatment of disease states such as cancer in which EGFR and / or activating mutations of EGFR and / or resistance mutations of EGFR are implicated. In one aspect, the present invention relates to the compounds of the formula (A): wherein, R1 is selected from one or more hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, C1-C6 alkoxy, hydroxyl, hydroxylalkyl, halo, cycloalkyloxy, cyano, nitro or amino; or two R1 groups to which they are attached to form substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroarylalkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, -C(O)- alkyl, -C(O)-aryl -S(O)2-alkyl, S(O)2-N(Ra)(Rb), -S(O)2-aryl, or hydroxylalkyl; R3 is selected from one or more C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxyl or nitro; and ‘A’ is selected from C1-C6alkyl, substituted or unsubstituted C3-C6cycloalkyl, , , substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl 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, the present invention relates to the compounds of the formula (I): Formula (I) wherein, ‘X’ is selected from substituted or unsubstituted heterocyclyl, -N(Ra)(Rb) or - ORa; wherein the substituents are selected from C1-C6alkyl, C3-C6cycloalkyl, C1-C6haloalkyl, heterocyclyl, -N(Ra)(Rb), hydroxyl, halo, cyano, amino or nitro; R1 is selected from one or more hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, C1-C6 alkoxy, hydroxyl, hydroxylalkyl, halo, cycloalkyloxy, cyano, nitro or amino; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, -C(O)-alkyl, -C(O)-aryl -S(O)2-alkyl, S(O)2-N(Ra)(Rb), -S(O)2-aryl, or hydroxylalkyl; R3 is selected from one or more C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxy or nitro; R4 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 deuteroalkyl, -C(O)-alkyl or -C(O)(O)-alkyl; wherein the substituents are selected from C1-C6 alkoxy, halo, cyano or amino; R5 is selected from C1-C6 alkyl, C2-C6 alkenyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1- C6 alkoxy or cycloalkyloxy; Ra and Rb are independently selected from hydrogen, substituted or unsubstituted C1- C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted cycloalkyloxy or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are selected from C1-C6 alkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxyl, or C1-C6 alkylamino; ‘m’ is an integer selected from 1, 2, 3 or 4; and ‘n’ is an integer selected from 0, 1, or 2; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof. According to another embodiment, there is provided a compound of Formula (I), wherein R1 is halo; wherein the said halo is selected from one or more fluoro or chloro. According to another embodiment, there is provided a compound of Formula (I), wherein R1 is hydrogen. According to yet another embodiment, there is provided a compound of Formula (I), wherein R1 is C1-C6 alkyl; wherein the said C1-C6 alkyl is selected from methyl, ethyl, isopropyl, n-butyl or tert-butyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R1 is C1-C6 haloalkyl; wherein the said C1-C6 haloalkyl is -CF3, -CH2CF3, CHF2 or CH2F. According to yet another embodiment, there is provided a compound of Formula (I), wherein R1 C1-C6 alkoxy; wherein the said C1-C6 alkoxy is -OCH3, -OCH2CH3, or - CH(CH3)CH3. According to yet another embodiment, there is provided a compound of Formula (I), wherein R2 is hydrogen. According to yet another embodiment, there is provided a compound of Formula (I),wherein R2 is C1-C6 alkyl; wherein the said C1-C6 alkyl is selected from methyl, ethyl,isopropyl, n-butyl or tert-butyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R2 is C1-C6 haloalkyl; wherein the said C1-C6 haloalkyl is -CH2CF3, CHF2 or CH2F. According to yet another embodiment there is provided a compound of Formula (I), wherein R2 is C1-C6 deuteroalkyl; wherein the said C1-C6 deuteroalkyl is deuteromethyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R2 C3-C6 cycloalkyl; wherein the said C3-C6 is cyclopropyl or cyclopbutyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R3 is hydrogen. According to yet another embodiment, there is provided a compound of Formula (I), wherein R3 is halo; wherein the said halo is selected from one or more fluoro or chloro. According to yet another embodiment, there is provided a compound of Formula (I), wherein R4 is C1-C6 alkyl; wherein the said C1-C6 alkyl is selected from methyl, ethyl, isopropyl, n-butyl or tert-butyl and the said alkyl is further substituted by alkoxy (methoxy). According to yet another embodiment, there is provided a compound of Formula (I), wherein R4 is C1-C6 haloalkyl; wherein the said C1-C6 haloalkyl is -CF3, -CH2CF3, CHF2 or CH2F. According to yet another embodiment, there is provided a compound of Formula (I), wherein R4 is C1-C6 deuteroalkyl; wherein the said C1-C6 deuteroalkyl is deuteromethyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R5 is C1-C6 alkyl; wherein the said C1-C6 alkyl is selected from methyl, ethyl, isopropyl, n-butyl or tert-butyl. According to yet another embodiment, there is provided a compound of Formula (I), wherein R5 is C1-C6 haloalkyl; wherein the said C1-C6 haloalkyl is -CH2-CH2-Cl. According to yet another embodiment, there is provided a compound of Formula (I), wherein ‘X’ is substituted heterocyclyl; wherein the said heterocyclyl is selected from , and the substituents are selected from methyl, ethyl, hydroxy, or According to yet another embodiment, there is provided a compound of Formula (I), wherein ‘X’ is -N(Ra)(Rb); wherein the said -N(Ra)(Rb) is selected from , According to yet another embodiment, there is provided a compound of Formula (I), wherein ‘X’ is -O(Ra); wherein - Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (IA): wherein, R1, R2, R4, R5, ‘m’ and ‘X’ are as defined in compound Formula (I). Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (IB): wherein, R1, R2, R4, R5, Ra, Rb and ‘m’ are as defined in compound Formula (I). Accordingly, to yet another embodiment the compound of Formula (I) is a compound of Formula (IC): wherein, R1, R2, Ra, Rb and ‘m’ are as defined in compound Formula (I). Accordingly, to yet another embodiment, the compound of Formula (I) is a compound of Formula (ID): where in, R1, R2, and ‘m’ are as defined in compound Formula (I). According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC) and (ID) R1 is hydrogen. According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC) and (ID) R1 is one or more fluoro or chloro. According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC) and (ID) R2 methyl. According to yet another embodiment, there is provided a compound of Formula (I), (IA), (IB), (IC) and (ID) R2 -CH2CF3. According to yet another embodiment, there is provided a compound of Formula (I), According to yet another embodiment, there is provided a compound of Formula (I), (IA) or (IB) R4 is methoxy. According to yet another embodiment, there is provided a compound of Formula (I),(IA) or (IB) R5 is ethenyl In further yet another embodiment, the compounds of formula (I) structurally encompass all stereoisomers, enantiomers and diastereomers, regioisomers and pharmaceutically acceptable salts that may be contemplated from the chemical structure of the general formula (I) described herein. The compounds of the present invention may exist in the form of regioisomers as described below and structures are confirmed by NOE technique (Nuclear Overhauser Effect). 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 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): N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propenamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propionamide, N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- morpholinophenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acetamide, N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)acrylamide, 3-chloro-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-morpholinophenyl)propenamide, 3-chloro-N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propenamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-5-((4-(5-fluoro-1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, (S)-N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 4-methoxy-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide, N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxy-2-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)acrylamide, N-(4-methoxy-2-(methyl(2-morpholinoethyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-((2- (dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-5- (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1-methyl- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)propenamide, 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)propenamide, N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, 3-chloro-N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)propenamide, 3-chloro-N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)propenamide, 2-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acetamide, N-(2-((2-(1,1-dioxidothiomorpholino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-hydroxyethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-ethyl-5-fluoro-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-isopropyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((3-(dimethylamino)propyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(diethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propenamide, N-(5-((4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, (S)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, (R)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- (4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)acrylamide, (R)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide, (S)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide, N-(2-(4-ethylpiperazin-1-yl)-4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(4-methoxy-2-((2-methoxyethyl)(methyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, tert-butyl (2-((2-acrylamido-5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)(methyl)carbamate, N-(4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5-chloro-7-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide, N-(5-((4-(6-chloro-4-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-ethyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-((2- (dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(methyl-d3)- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2,2,2- trifluoroethoxy)phenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2,2,2-trifluoroethoxy)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2,2,2-trifluoroethoxy)-5-((4-(1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-(2,2,2-trifluoroethoxy)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2-methoxyethoxy)-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2-methoxyethoxy)-5-((4-(1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(methoxy-d3)-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(6-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-fluoro-1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxyphenyl)acrylamide, N-(2-(4-(dimethylamino)piperidin-1-yl)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-(4-(dimethylamino)piperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-4-methoxy-2-(4-methylpiperazin-1-yl)phenyl)acrylamide, N-(4-methoxy-2-(4-methylpiperazin-1-yl)-5-((4-(1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-(3-(dimethylamino)azetidin-1-yl)-4-methoxyphenyl)acrylamide, N-(2-(3-(dimethylamino)azetidin-1-yl)-4-methoxy-5-((4-(1-(2,2,2-trifluoroethyl)- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-ethyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, N-(2-(2-(dimethylamino)ethoxy)-4-methoxy-5-((4-(1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, and N-(5-((4-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-(4- (dimethylamino)piperidin-1-yl)-4-methoxyphenyl)acrylamide, 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 benzimidazole 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. As used herein, "cycloalkyloxy" refers to an -O-cycloalkyl group wherein the cycloalkyl group is as defined above. The term "Deuteroalkyl” refers to an alkyl radical, as defined above, that is substituted by one or more deuterium atoms. In some embodiments, the alkyl is substituted with one deuterium atom. In some embodiments, the alkyl is substituted with one, two, or three deuterium atoms. In some embodiments, the alkyl is substituted with one, two, three, four, five, or six deuterium atoms. Deuteroalkyl includes, for example, CD3, CH2D, CHD2, CH2CD3, CD2CD3, CHDCD3, CH2CH2D, or CH2CHD2. The term “amino” represents -NH2. The term “alkylamino” represents at least one of the hydrogens in amino are replaced by alkyl. Examples of alkylamino includes -NH(CH3), -N(CH3)(CH3) or -NHCH2CH3) - N(CH2CH3)(CH2CH3). Alkyl and amino are as defined herein. 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 “hydroxyalkyl” refers to a linear monovalent hydrocarbon radical of carbon atoms or a branched monovalent hydrocarbon radical of three to six carbons substituted with one or two hydroxy groups such as but not limited to -CH2-OH, –CH2-CH2-OH, CH(CH3)- OH and -CH2-CH(CH3)-OH. 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 “heteroarylalkyl” refers to a heteroaryl group as defined above linked through a C-atom or heteroatom to an alkyl chain as defined above. 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 methylmorpholinyl, methylpiperazinyl, ethylmorpholinyl, ethyl piperazinyl, ethylthiomorpholindioxide, 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 EGFR. The present disclosure relates to benzimidazole compounds for use in modulating kinase enzymatic activity and accordingly modulating kinase-dependent associated diseases and conditions such as cancers like lung, head and neck, gastroesophageal, and colorectal cancers, and has been associated with proliferation, invasion, and metastasis. 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 lung 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) and (ID) 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) and (ID) 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. The general methods of synthesizing the compounds of the present invention are depicted below. Scheme-1:

[0002] The compound of formula (i) was converted to the compound of formula (ii) by using L-lactic acid under acidic conditions with reagents like Aq. con. HCl or the like at heating conditions. The compound of formula (i) was also converted to the compound of formula (ii) by using L-lactic acid under acidic conditions with reagents like PTSA, lactic acid or the like in solvents like toluene, xylene or the like at heating conditions. The compound of formula (ii) was converted to the compound of formula (iii) by using oxidising agents such as K2Cr2O7 or the like under acidic conditions with acetic acid or the like at heating conditions. The compound of formula (iii) was converted to the compound of formula (iv) by using R2-OTs, R2-OMs, R2-OTf, R2-I, R2-Br, R2-Cl or the like under basic conditions with reagents like Na2CO3, K2CO3, Cs2CO3, KOtBu, NaH or the like in solvents such as DMF, DMA, THF, ACN, 1,4-dioxane or the like at heating conditions. The compound of formula (iv) was converted to the compound of formula (v) by using DMFDMA or the like at heating conditions. The compound of formula (iv) was also converted to the compound of formula (v) by using DMFDMA under basic conditions with reagents like Na2CO3, K2CO3, Cs2CO3, KOtBu, NaH or the like in solvents such as DMF, THF, ACN, 1,4-dioxane or the like at room temperature. The compound of formula (vi) was converted to the compound of formula (vii) by using Aq, NH2CN under acidic conditions with Aq. Con. HCl or the like in solvents such as EtOH, isopropanol, n-butanol or the like at heating conditions. The compound of formula (vii) was converted to the compound of formula (viii) by nucleophilic displacement of fluorene with nucleophile X under basic conditions with reagents N(Et)3, DIPEA, Na2CO3, K2CO3, Cs2CO3, KOtBu, NaH or the like in solvents such as DMF, DMA, ACN, THF, 1,4- dioxane or the like at heating or room temperature conditions. The compound of formula (viii) was converted to the compound of formula (ix) by using formula (v) under basic conditions with reagents like Na2CO3, K2CO3, Cs2CO3or the like in solvents such as n-butanol, EtOH, isopropanol or the like at heating conditions. The compound of formula (ix) was converted to the compound of formula (x) by using the reducing agent such as Iron powder, under acidic conditions with reagents like acetic acid, ammonium chloride or the like in solvents such as methanol, ethanol or the like and water or the like at heating conditions. The compound of formula (ix) was also converted to the compound of formula (x) by using Pd / C, Pt / C, Raney Ni or the like under hydrogen atmosphere in solvents such as MeOH, EtOH or the like and EtOAc, THF or the like at room temperature conditions. The compound of formula (x) was also converted to the compound of formula (I) by using acryloyl chloride under basic conditions with reagents N(Et)3, DIPEA or the like in solvents such as DCM, THF or the like at 0°C to room temperature conditions. 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), DMSO-d6 (Dimethylsulfoxide-d6); s (singlet); d (doublet); t (triplet); q (quartet); m (multiplet); dd (doublet of doublet(s)); J (coupling constant); 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)); 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); ACN (acetonitrile); DMFDMA (N,N-dimethylformamide dimethyl acetal); Na2SO4 (sodium sulphate); HCl (Hydrochloric acid); TLC (Thin Layer Chromatography); % (percentage); MTBE (Methyl tert-butyl ether); h (or) hrs (hour(s)); H (Hydrogen); DIPEA (N,N-Diisopropylethylamine or N-ethyl-N-isopropylpropan-2-amine); Et3N (Triethylamine); Pd / C (Palladium on Carbon); Pt / C (Platinum on Carbon); EtOAc (Ethyl acetate); Ltr (Liter / Litre), NaHCO3 (sodium bicarbonate); K2CO3 (potassium carbonate); Na2CO3 (sodium carbonate); Cs2CO3 (cesium carbonate); KOtBu (potassium tertiary butoxide); NaH (sodium hydride); PTSA (p-toluenesulfonic acid); K2Cr2O7 (potassium dichromate); EtOH (ethanol); NH2CN (cyanamide). 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 (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2- yl)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of benzene-1,2-diamine (20 g, 184.94 mmol, 1.0 eq), L-Lactic acid (17.91 ml, 240.42 mmol, 1.3 eq) and concentrated HCl (38 ml) was stirred and heated at 95 ºC for about 8 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (27.0 g, yield: 73.3%) as a solid.1H-NMR (500 MHz-DMSO-d6): 12.21 (brs, 1H), 7.48 (m, 2H), 7.12 (m, 2H), 5.73 (d, J = 5.0 Hz, 1H), 4.93 (m, 1H), 1.50 (d, J = 6.5 Hz, 3H). Step 2: Synthesis of 1-(1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 1, 27 g, 166.4 mmol, 1.0 eq) in acetic acid (270 ml) was added potassium dichromate (58.76 g, 199.7 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (400 ml) and washed with water (400 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (21 g, yield: 78.94%) as a solid.1H-NMR (500 MHz-DMSO-d6): 13.27 (brs, 1H), 7.81 (m, 1H), 7.55 (m, 1H), 7.37 (m, 1H), 7.31 (m, 1H), 2.70 (s, 3H). Step 3: Synthesis of 1-(1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of 1-(1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 21.0 g, 131.10 mmol, 1.0 eq) in aqueous 2N NaOH (548 ml) was added dimethyl sulphate (24.86 ml, 262.2 mmol, 2.0 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 cooled to 0 ºC, acidified with 1N HCl and extracted with ethyl acetate (400 ml). The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (13.0 g, yield: 57%) as a solid. Step 4: Synthesis of (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2- en-1-one: A mixture of 1-(1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 3, 13 g, 74.62 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (97 ml) were heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (7 g, yield: 40.0%) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 7.80 (m, 1H), 7.73 (m, 1H), 7.61 (m, 1H), 7.35 (m, 1H), 7.28 (m, 1H), 6.26 (m, 1H), 4.11 (s, 3H), 3.19 (s, 3H), 2.94 (s, 3H). Intermediate 2: Preparation of (E)-1-(1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2- en-1-one: A mixture of 1-(1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 1-step 2, 8 g, 49.6 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (60 ml) were heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (5.8 g, yield: 54.2%) as an off-white solid. Mass m / z: 216.27 (M+H)+. Intermediate 3: Preparation of (E)-3-(dimethylamino)-1-(1-methyl-5-(trifluoromethyl)-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethan-1- ol: A mixture of N1-methyl-4-(trifluoromethyl)benzene-1,2-diamine (5 g, 26.2 mmol, 1.0 eq), L-Lactic acid (2.6 ml, 34.1 mmol, 1.3 eq) and concentrated HCl (15 ml) was stirred and heated at 95 ºC for about 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (4.1 g, yield: 65.6%) as a solid. Mass m / z: 245.12 (M+H)+. To a stirred solution of (S)-1-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol- 2-yl)ethan-1-ol (Step 1, 4.0 g, 16.8 mmol, 1.0 eq) in acetic acid (40 ml) was added potassium dichromate (5.8 g, 19.6 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (3.8 g, yield: 95.6%) as a solid.1H-NMR (500 MHz-DMSO-d6): 8.24 (s, 1H), 7.95 (d, J= 8.5 Hz, 1H), 7.75 (d, J = 8.5 Hz, 1H), 4.11 (s, 3H), 2.75 (s, 3H). Step 3: Synthesis of (E)-3-(dimethylamino)-1-(1-methyl-5-(trifluoromethyl)-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: A mixture of 1-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)ethan-1- one (Step 2, 4.5 g, 18.5 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (36 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (4.4 g, yield: 80.0%) as an off- white solid.1H-NMR (500 MHz-DMSO-d6): 8.12 (s, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.83 (m, 1H), 7.66 (d, J = 8.5 Hz, 1H), 6.24 (m, 1H), 4.15 (s, 3H), 3.21 (s, 3H), 2.95 (s, 3H); Mass m / z: 298.14 (M+H)+. Intermediate 4: Preparation of (E)-1-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)-3-(dimethylamino)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(5-chloro-7-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of 5-chloro-3-fluorobenzene-1,2-diamine (3 g, 18.7 mmol, 1.0 eq), L- Lactic acid (1.9 ml, 24.3 mmol, 1.3 eq) and concentrated HCl (10 ml) was stirred and heated at 95 ºC for about 8 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (3.45 g, yield: 86%) as a solid.1H-NMR (500 MHz-DMSO-d6): 12.75 (brs, 1H), 7.34 (d, J = 1.5 Hz, 1H), 7.11 (dd, J = 1.5 Hz, 10.5 Hz, 1H), 5.87 (d, J = 3.5 Hz, 1H), 4.93 (m, 1H), 1.50 (d, J = 7.0 Hz, 3H); Mass m / z: 215.13 (M+H)+. Step 2: Synthesis of 1-(5-chloro-7-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(5-chloro-7-fluoro-1H-benzo[d]imidazol-2-yl)ethan- 1-ol (Step 1, 3.4 g, 15.8 mmol, 1.0 eq) in acetic acid (34 ml) was added potassium dichromate (5.6 g, 19.0 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (3.3 g, yield: 98.2%) as a solid.1H-NMR (500 MHz-DMSO-d6): 13.75 (brs, 1H), 7.41 (s, 1H), 7.32 (d, J = 10.5 Hz, 1H), 2.70 (s, 3H); Mass m / z: 213.08 (M+H)+. Step 3: Synthesis of 1-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Isomer 1) and 1-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Isomer 2): To a stirred solution of 1-(5-chloro-7-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1- one (Step 2, 3.2 g, 15.0 mmol, 1.0 eq) in aqueous 2N NaOH (96 ml) was added dimethyl sulphate (2.86 ml, 30.0 mmol, 2.0 eq). The reaction mixture was stirred at room temperature for about 4 hours. TLC indicated starting material was consumed and the desired products were observed. The reaction mixture was cooled to 0 ºC, acidified with 1N HCl and extracted with ethyl acetate (100 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (0.88 g, yield: 26.0%) and Isomer 2 (1.32 g, yield: 38.8%) as solids. Isomer 1:1H-NMR (500 MHz-DMSO-d6): 7.77 (d, J = 1.5 Hz, 1H), 7.43 (dd, J = 1.5Hz, 12.0 Hz, 1H), 4.18 (s, 3H), 2.71 (s, 3H); Mass m / z: 227.16 (M+H)+. Isomer 2:1H-NMR (500 MHz-DMSO-d6): 7.81 (d, J = 1.5 Hz, 1H), 7.36 (dd, J = 1.5Hz, 10.5 Hz, 1H), 4.05 (s, 3H), 2.72 (s, 3H); Mass m / z: 227.16 (M+H)+. Step 4: Synthesis of (E)-1-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1- one (Step 3-Isomer 1, , 0.5 g, 2.2 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (5 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.5 g, yield: 81.0%) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 7.83 (d, J = 12.5 Hz, 1H), 7.66 (d, J = 1.5 Hz, 1H), 7.33 (dd, J = 1.5 Hz, 11.5 Hz, 1H), 6.16 (m, 1H), 4.25 (s, 3H), 3.20 (s, 3H), 2.94 (s, 3H); Mass m / z: 282.14 (M+H)+. Intermediate 5: Preparation of (E)-1-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)-3-(dimethylamino)prop-2-en-1-one: A mixture of 1-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1- one (Intermediate 4-step 3-Isomer 2, 0.5 g, 2.2 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (5 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.51 g, yield: 82.0%) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 7.83 (d, J = 12.5 Hz, 1H), 7.70 (d, J = 1.5 Hz, 1H), 7.27 (dd, J = 1.5 Hz, 10.5 Hz, 1H), 6.19 (m, 1H), 4.09 (s, 3H), 3.20 (s, 3H), 2.95 (s, 3H); Mass m / z: 282.07 (M+H)+. Intermediate 6: Preparation of (E)-3-(dimethylamino)-1-(1-ethyl-5-fluoro-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(1-ethyl-5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of N1-ethyl-4-fluorobenzene-1,2-diamine (2 g, 12.9 mmol, 1.0 eq), L- Lactic acid (1.3 ml, 16.8 mmol, 1.3 eq) and concentrated HCl (10 ml) was stirred and heated at 95 ºC for about 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (1.9 g, yield: 71.0%) as a solid.1H-NMR (500 MHz-DMSO-d6): 7.56 (dd, J = 4.5 Hz, 8.5 Hz, 1H), 7.40 (dd, J = 2.5 Hz, 9.5 Hz, 1H), 7.08 (m, 1H), 5.63 (d, J = 6.5 Hz, 1H), 5.02 (m, 1H), 4.38 (m, 2H), 1.58 (d, J = 6.5 Hz, 3H), 1.34 (t, J = 7.0 Hz, 3H); Mass m / z: 209.18 (M+H)+. Step 2: Synthesis of 1-(1-ethyl-5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(1-ethyl-5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1- ol (Step 1, 3.0 g, 14.4 mmol, 1.0 eq) in acetic acid (30 ml) was added potassium dichromate (5.0 g, 17.2 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (2.2 g, yield 74.1%) as a solid.1H-NMR (500 MHz-DMSO-d6): 7.81 (dd, J = 4.0 Hz, 8.5 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.35 (t, J = 8.5 Hz, 1H), 4.60 (q, J = 6.0 Hz, 2H), 2.73 (s, 3H), 1.33 (t, J = 6.0 Hz, 3H). Step 3: Synthesis of (E)-3-(dimethylamino)-1-(1-ethyl-5-fluoro-1H-benzo[d]imidazol-2- yl)prop-2-en-1-one: A mixture of 1-(1-ethyl-5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 2.2 g, 10.6 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (22 ml) was heated at 100- 120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (1.2 g, yield: 43.2%) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 7.82 (d, J = 12.5 Hz, 1H), 7.69 (dd, J = 5.0 Hz, 9.0 Hz, 1H), 7.54 (dd, J = 2.0 Hz, 10.0 Hz, 1H), 7.22 (m, 1H), 6.24 (m, 1H), 4.68 (m, 2H), 3.20 (s, 3H), 2.94 (s, 3H), 1.32 (t, J = 7.0 Hz, 3H); Mass m / z: 262.17 (M+H)+. Intermediate 7: Preparation of (E)-3-(dimethylamino)-1-(1-isopropyl-1H-benzo[d]imidazol- 2-yl)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(1-isopropyl-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of N1-isopropylbenzene-1,2-diamine (2 g, 13.3 mmol, 1.0 eq), L-Lactic acid (1.6 ml, 17.3 mmol, 1.3 eq) and concentrated HCl (10 ml) was stirred and heated at 95 ºC for about 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (0.8 g, yield: 29.5%) as a solid. Mass m / z: 205.21 (M+H)+. Step 2: Synthesis of 1-(1-isopropyl-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(1-isopropyl-1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 1, 0.8 g, 3.9 mmol, 1.0 eq) in acetic acid (10 ml) was added potassium dichromate (1.38 g, 4.7 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (50 ml) and washed with water (50 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (0.65 g, yield: 82.2 %) as a solid. Mass m / z: 203.16 (M+H)+. Step 3: Synthesis of (E)-3-(dimethylamino)-1-(1-isopropyl-1H-benzo[d]imidazol-2-yl)prop- 2-en-1-one: A mixture of 1-(1-isopropyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 0.65 g, 3.2 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (8 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.675 g, yield: 81.7%) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 7.74 (m, 3H), 7.26 (m, 2H), 6.15 (m, 1H), 5.91 (m, 1H), 3.17 (s, 3H), 2.92 (s, 3H), 1.56 (d, J = 7.0 Hz, 6H); Mass m / z: 258.28 (M+H)+. Intermediate 8: Preparation of (E)-1-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(5,7-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of 3,5-difluorobenzene-1,2-diamine (5 g, 34.6 mmol, 1.0 eq), L-Lactic acid (5.19 ml, 69.3 mmol, 2.0 eq) and concentrated HCl (25 ml) was stirred and heated at 95 ºC for about 8 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (6.5 g, yield: 95%) as a solid. Mass m / z: 199.13 (M+H)+. Step 2: Synthesis of 1-(5,7-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(5,7-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 1, 6.5 g, 32.8 mmol, 1.0 eq) in acetic acid (65 ml) was added potassium dichromate (11.58 g, 39.3 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (5.8 g, yield: 90.6 %) as a solid. Mass m / z: 196.94 (M+H)+. Step 3: Synthesis of 1-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan- 1-one (Isomer 1) and 1-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Isomer 2): and To a stirred solution of 1-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 3.5 g, 17.8 mmol, 1.0 eq) in DMF (35 ml) were added K2CO3 (4.92 g, 35.7 mmol, 2.0 eq) and 1,1,1-trifluoro-2-iodoethane (6.96 ml, 71.4 mmol, 4.0 eq). The reaction mixture was stirred at 90 ºC for about 16 hours. TLC indicated starting material was consumed and the desired products were observed. The reaction mixture was cooled to room temperature and extracted with ethyl acetate (100 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (0.89 g, yield: 18.0%) and Isomer 2 (1.34 g, yield: 26.8%) as solids. Isomer 1:1H-NMR (500 MHz-DMSO-d6): 7.68 (m, 1H), 7.54 (m, 1H), 5.59 (m, 2H), 2.76 (s, 3H); Mass m / z: 279.12 (M+H)+. Isomer 2:1H-NMR (500 MHz-DMSO-d6): 7.72 (m, 1H), 7.38 (m, 1H), 5.63 (m, 2H), 2.75 (s, 3H); Mass m / z: 279.16 (M+H)+. Step 4: Synthesis of (E)-1-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)- 3-(dimethylamino)prop-2-en-1-one: A mixture of 1-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Step 3-Isomer 1, 0.45 g, 1.6 mmol) and dimethylformamide dimethyl acetal (10 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.4 g, yield: 74.21%) as an off-white solid. Mass m / z: 334.05 (M+H)+. Intermediate 9: Preparation of (E)-1-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one: A mixture of 1-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Intermediate 8-step 3-Isomer 2, 0.7 g, 2.5 mmol) and dimethylformamide dimethyl acetal (7 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.65 g, yield: 77.5%) as an off-white solid. Mass m / z: 334.05 (M+H)+. Intermediate 10: Preparation of (E)-1-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: Step 1: Synthesis of 1-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Isomer 1) and 1-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Isomer 2): and To a stirred solution of 1-(5,7-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 8-step 2, 6.1 g, 31.1 mmol, 1.0 eq) in aqueous 2N NaOH (183 ml) was added dimethyl sulphate (6.04 ml, 124.5 mmol, 4.0 eq). The reaction mixture was stirred at room temperature for about 18 hours. TLC indicated starting material was consumed and the desired products were observed. The reaction mixture was cooled to 0 ºC, acidified with 1N HCl and extracted with ethyl acetate (500 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (1.4 g, yield: 21.5%) and Isomer 2 (2.4 g, yield: 36.9%) as solids. Isomer 1:1H-NMR (500 MHz-DMSO-d6): 7.53 (m, 1H), 7.37 (m, 1H), 4.19 (s, 3H), 2.71 (s, 3H); Mass m / z: 211.09 (M+H)+. Isomer 2:1H-NMR (500 MHz-DMSO-d6): 7.56 (m, 1H), 7.26 (m, 1H), 4.03 (s, 3H), 2.71 (s, 3H); Mass m / z: 211.03 (M+H)+. Step 2: Synthesis of (E)-1-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 1-Isomer 1, 0.7 g, 3.3 mmol) and dimethylformamide dimethyl acetal (7 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.7 g, yield: 79.2%) as an off-white solid. Mass m / z: 266.14 (M+H)+. Intermediate 11: Preparation of (E)-1-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 10-Step 1-Isomer 2, 1.2 g, 5.7 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (12 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.8 g, yield: 52.9%) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 7.84 (d, J = 12.5 Hz, 1H), 7.46 (m, 1H), 7.16 (m, 1H), 6.18 (m, 1H), 4.07 (s, 3H), 3.20 (s, 3H), 2.95 (s, 3H); Mass m / z: 266.14 (M+H)+. Intermediate 12: Preparation of (E)-3-(dimethylamino)-1-(5-fluoro-1-methyl-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: A mixture of 4-fluoro-N1-methylbenzene-1,2-diamine (11 g, 78.5 mmol, 1.0 eq), L-Lactic acid (7.61 ml, 102.1 mmol, 1.3 eq) and concentrated HCl (33 ml) was stirred and heated at 95 ºC for about 8 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (9.0 g, yield: 59.05%) as a solid. Mass m / z: 195.27 (M+H)+. To a stirred solution of (S)-1-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan- 1-ol (Step 1, 9.0 g, 46.3 mmol, 1.0 eq) in acetic acid (90 ml) was added potassium dichromate (16.37 g, 55.6 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (400 ml) and washed with water (400 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (4 g, yield: 44.94%) as a solid. Mass m / z: 193.22 (M+H)+. Step 3: Synthesis of (E)-3-(dimethylamino)-1-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)prop-2-en-1-one: A mixture of 1-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 4 g, 20.8 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (32 ml) was heated at 100- 120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (4.5 g, yield: 87.5%) as an off-white solid. Mass m / z: 248.32 (M+H)+. Intermediate 13: Preparation of (E)-1-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of 4,5-difluorobenzene-1,2-diamine (5 g, 34.7 mmol, 1.0 eq), L-Lactic acid (4.1 g, 45.1 mmol, 1.3 eq) and concentrated HCl (15 ml) was stirred and heated at 95 ºC for about 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (4.3 g, yield: 62.59%) as a solid. Mass m / z: 199.16 (M+H)+. Step 2: Synthesis of 1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 1, 4.3 g, 21.7 mmol, 1.0 eq) in acetic acid (43 ml) was added potassium dichromate (7.66 g, 26.0 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (150 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (3.2 g, yield: 75.29%) as a solid. Mass m / z: 197.21 (M+H)+. To a stirred solution of 1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 3.2 g, 16.3 mmol, 1.0 eq) in aqueous 2N NaOH (96 ml) was added dimethyl sulphate (3.1 ml, 32.6 mmol, 2.0 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 cooled to 0 ºC, acidified with 1N HCl and extracted with ethyl acetate (200 ml). The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (2.3 g, yield: 67.25%) as a solid. Mass m / z: 211.22 (M+H)+. Step 4: Synthesis of (E)-1-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 3, 2.3 g, 10.9 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (20 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (2.7 g, yield: 93.10%) as an off-white solid. Mass m / z: 266.26 (M+H)+. Intermediate 14: Preparation of (E)-1-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one: Step 1: Synthesis of 1-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan- 1-one: To a stirred solution of 1-(5,6-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 13-step 2, 4.7 g, 23.9 mmol, 1.0 eq) in DMF (50 ml) were added K2CO3 (9.92 g, 71.9 mmol, 3.0 eq) and 2,2,2-trifluoroethyl 4-methylbenzenesulfonate (6.69 g, 26.3 mmol, 1.1 eq). The reaction mixture was heated to 90 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with MTBE (200 ml) and washed with water (100 ml) and brine solution (100 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 30-40% EtOAc in n-hexane gradient to obtain the title compound (2.5 g, yield: 37.8%) as a solid. Mass m / z: 279.21 (M+H)+. Step 2: Synthesis of (E)-1-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)- 3-(dimethylamino)prop-2-en-1-one: A mixture of 1-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Step 1, 2.5 g, 8.9 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (20 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (1.8 g, yield: 62.0%) as an off-white solid. Mass m / z: 334.14 (M+H)+. Intermediate 15: Preparation of (E)-1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 4-chloro-N1-methylbenzene-1,2-diamine (3 g, 19.2 mmol, 1.0 eq), L- Lactic acid (1.86 ml, 24.9 mmol, 1.3 eq) and concentrated HCl (6 ml) was stirred and heated at 95 ºC for about 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (3 g, yield: 74.43%) as a solid. Mass m / z: 211.43 (M+H)+. To a stirred solution of (S)-1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan- 1-ol (Step 1, 4 g, 19.0 mmol, 1.0 eq) in acetic acid (40 ml) was added potassium dichromate (6.71 g, 22.8 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (3.1 g, yield: 78.27%) as a solid. Mass m / z: 209.13 (M+H)+. Step 3: Synthesis of (E)-1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 5.0 g, 24.0 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (40 ml) was heated at 100- 120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (5.0 g, yield: 79.11%) as an off-white solid. Mass m / z: 264.14 (M+H)+. Intermediate 16: Preparation of (E)-1-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of 5-chloro-N1-methylbenzene-1,2-diamine (2.0 g, 12.8 mmol, 1.0 eq), L-Lactic acid (1.24 ml, 16.6 mmol, 1.3 eq) and concentrated HCl (6 ml) was stirred and heated at 95 ºC for about 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for about 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (2.3 g, yield: 85.5%) as a solid. Mass m / z: 211.09 (M+H)+. To a stirred solution of (S)-1-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan- 1-ol (Step 1, 2.3 g, 10.9 mmol, 1.0 eq) in acetic acid (23 ml) was added potassium dichromate (3.86 g, 13.1 mmol, 1.2 eq). The reaction mixture was heated at 60 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (2.0 g, yield: 88.0%) as a solid. Mass m / z: 209.11 (M+H)+. Step 3: Synthesis of (E)-1-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 2.0 g, 9.61 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (16 ml) was heated at 100- 120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (1.3 g, yield: 51.58%) as an off-white solid. Mass m / z: 264.29 (M+H)+. Intermediate 17: Preparation of (E)-3-(dimethylamino)-1-(1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl) 2-en-1-one: Step 1: Synthesis of 1-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of 1-(1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 1- step 2, 2.0 g, 12.5 mmol, 1.0 eq) in DMF (20 ml) were added K2CO3 (3.45 g, 25.0 mmol, 2.0 eq) and 1,1,1-trifluoro-2-iodoethane (10.5 g, 50.0 mmol, 4.0 eq). The reaction mixture was heated to 90 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with MTBE (100 ml) and washed with water (50 ml) and brine solution (30 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 30-40% EtOAc in n-hexane gradient to obtain the title compound (1.8 g, yield: 60.0%) as a solid. Mass m / z: 243.09 (M+H)+. Step 2: Synthesis of (E)-3-(dimethylamino)-1-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol- 2-yl)prop-2-en-1-one: A mixture of 1-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 1, 1.8 g, 7.43 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (15 ml) was heated at 100-120 ºC for about 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (1.7 g, yield: 77.0%) as an off-white solid. Mass m / z: 298.08 (M+H)+. Intermediate 18: Preparation of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine: To a stirred solution of 4-fluoro-2-methoxy-5-nitroaniline (10.0 g, 53.72 mmol, 1.0 eq) in ethanol (60 ml) and water (12 ml) were added concentrated HCl (10 ml) and cyanamide solution (27.2 ml, 50% aqueous solution). The reaction mixture was heated at 75 ºC for about 24 hours. The reaction mixture was cooled to room temperature, ice water was added and stirred for about 30 minutes. The resulting solution was filtered and the filtrate was adjusted to pH >12 by using aqueous 25% NaOH solution and the obtained solid was collected by filtration and washed with water and dried under vacuum to give title compound (10.0 g, yield: 81%).1H-NMR (500 MHz-DMSO-d6): 7.33 (d, J = 4.5 Hz, 1H), 7.03 (d, J = 13.5 Hz, 1H), 5.24 (m, 4H), 3.81 (s, 3H). Step 2: Synthesis of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Step 1, 10 g, 43.825 mmol, 1.0 eq) in N,N-dimethylformamide (100 ml) were added K2CO3 (18.14 g, 131.475 mmol, 3.0 eq) and N1,N1,N2-trimethylethane-1,2-diamine (6.7 g, 65.737 mmol, 1.5 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 311.21 (M+H)+. Intermediate 19: of 1-(2-methoxy-4-morpholino-5- To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 2.0 g, 8.76 mmol, 1.0 eq) in N,N-dimethylformamide (20 ml) were added K2CO3(3.62 g, 26.295 mmol, 3.0 eq) and morpholine (1.2 ml, 13.147 mmol, 1.5 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Intermediate 20: Preparation of 1-(4-(4-hydroxypiperidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1.0 g, 4.382 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.81 g, 13.147 mmol, 3.0 eq) and piperidin-4-ol (0.66 g, 6.573 mmol, 1.5 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Intermediate 21: Preparation of 1-(2-methoxy-4-(methyl(2-morpholinoethyl)amino)-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.75 g, 3.28 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.50 g, 9.86 mmol, 3.0 eq) and N-methyl-2-morpholinoethan-1-amine (0.47 g, 3.28 mmol, 1.0 eq). The reaction mixture was heated to 90 ºC for about 16 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 353.26 (M+H)+. Intermediate 22: Preparation of 1-(4-((2-(1,1-dioxidothiomorpholino)ethyl)(methyl)amino)- 2-methoxy-5-nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.379 g, 1.66 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (0.689 g, 4.98 mmol, 3.0 eq) and 4-(2-(methylamino)ethyl)thiomorpholine 1,1- dioxide (0.382 g, 1.99 mmol, 1.2 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 401.05 (M+H)+. Intermediate 23: Preparation of 1-(4-((2-hydroxyethyl)(methyl)amino)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1.5 g, 6.5 mmol, 1.0 eq) in N,N-dimethylformamide (15 ml) were added K2CO3 (2.69 g, 19.5 mmol, 3.0 eq) and 2-(methylamino)ethan-1-ol (0.493 g, 6.5 mmol, 1.0 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 284.26 (M+H)+. Intermediate 24: Preparation of 1-(4-((3-(dimethylamino)propyl)(methyl)amino)-2-methoxy- To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.6 g, 2.6 mmol, 1.0 eq) in N,N-dimethylformamide (8 ml) were added K2CO3 (1.08 g, 7.8 mmol, 3.0 eq) and N1,N1,N3-trimethylpropane-1,3-diamine (0.305 g, 2.6 mmol, 1.0 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Intermediate 25: Preparation of 1-(4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.8 g, 3.50 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.45 g, 10.52 mmol, 3.0 eq) and N1,N1-diethyl-N2-methylethane-1,2-diamine (0.456 g, 3.50 mmol, 1.0 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 339.16 (M+H)+. Intermediate 26: Preparation of (S)-1-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1 g, 4.3 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.78 g, 12.9 mmol, 3.0 eq) and (S)-N,N-dimethylpyrrolidin-3-amine (0.51 g, 4.3 mmol, 1.0 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 323.27 (M+H)+. Intermediate 27: Preparation of (S)-1-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1- yl)-5-nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1 g, 4.3 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3(1.78 g, 12.9 mmol, 3.0 eq) and (S)-1-methyl-4-(pyrrolidin-3-yl)piperazine (0.74 g, 4.3 mmol, 1.0 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 378.18 (M+H)+. Intermediate 28: Preparation of 1-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)- 5-nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1 g, 4.3 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.78 g, 12.9 mmol, 3.0 eq) and 1-methyl-4-(piperidin-4-yl)piperazine (0.82 g, 4.3 mmol, 1.0 eq). The reaction mixture was heated to 90 ºC for about 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 392.31 (M+H)+. Intermediate 29: Preparation of (S)-1-(4-(3-hydroxypyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.8 g, 3.5 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.45 g, 10.52 mmol, 3.0 eq) and (S)-pyrrolidin-3-ol (0.52 g, 4.2 mmol, 1.2 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 295.98 (M+H)+. Intermediate 30: Preparation of (R)-1-(4-(3-hydroxypyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.8 g, 3.5 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.45 g, 10.52 mmol, 3.0 eq) and (R)-pyrrolidin-3-ol (0.52 g, 4.2 mmol, 1.2 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 296.12 (M+H)+. Intermediate 31: Preparation of (R)-1-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1- yl)-5-nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.9 g, 3.94 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.63 g, 11.83 mmol, 3.0 eq) and (R)-1-methyl-4-(pyrrolidin-3-yl)piperazine (0.66 g, 3.94 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 378.41 (M+H)+. Intermediate 32: Preparation of 1-(4-(4-ethylpiperazin-1-yl)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1.0 g, 4.38 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.81 g, 13.15 mmol, 3.0 eq) and 1-ethylpiperazine (0.75 g, 6.5 mmol, 1.5 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 323.24 (M+H)+. Intermediate 33: Preparation of 1-(2-methoxy-4-((2-methoxyethyl)(methyl)amino)-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1.5 g, 6.5 mmol, 1.0 eq) in N,N-dimethylformamide (15 ml) were added K2CO3 (2.72 g, 19.7 mmol, 3.0 eq) and 2-methoxy-N-methylethan-1-amine (0.59 g, 6.5 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 298.15 (M+H)+. Intermediate 34: Preparation of 1-(2-methoxy-4-(methyl(2-(methylamino)ethyl)amino)-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1.8 g, 7.8 mmol, 1.0 eq) in N,N-dimethylformamide (20 ml) were added K2CO3 (3.27 g, 23.6 mmol, 3.0 eq) and N1,N2-dimethylethane-1,2-diamine (0.85 ml, 7.8 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 297.21 (M+H)+. Intermediate 35: Preparation of (E)-1-(5-chloro-7-fluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one: Step 1: Synthesis of 1-(5-chloro-7-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Isomer 1) and 1-(6-chloro-4-fluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)ethan-1-one (Isomer 2): To a stirred solution of 1-(5-chloro-7-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1- one (Intermediate 4-step 2, 2 g, 9.4 mmol, 1.0 eq) in N,N-dimethylformamide (20 ml) were added K2CO3 (2.6 g, 18.8 mmol, 2.0 eq) and 1,1,1-trifluoro-2-iodoethane (3.7 ml, 37.7 mmol, 4.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (0.72 g, yield: 26.0%) and Isomer 2 (1.05 g, yield: 38.0%) as solids. Isomer 1:1H-NMR (500 MHz-DMSO-d6): 7.93 (d, J = 1.5 Hz, 1H), 7.64 (dd, J = 1.5 Hz, 11.5 Hz, 1H), 5.70 (m, 2H), 2.76 (s, 3H); Mass m / z: 294.92 (M+H)+. Isomer 2:1H-NMR (500 MHz-DMSO-d6): 7.97 (d, J = 1.5 Hz, 1H), 7.50 (dd, J = 1.5 Hz, 10.5 Hz, 1H), 5.65 (q, J = 9.0 Hz, 2H), 2.76 (s, 3H); Mass m / z: 295.13 (M+H)+. Step 2: Synthesis of (E)-1-(5-chloro-7-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol- 2-yl)-3-(dimethylamino)prop-2-en-1-one: A mixture of 1-(5-chloro-7-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Step 1-Isomer 1, 0.2 g, 0.6 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (2 ml) was heated at 100-120oC for 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.3 g, yield: 87.0%) as an off-white solid. Mass m / z: 350.13 (M+H)+. Intermediate 36: Preparation of (E)-1-(6-chloro-4-fluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one: A mixture of 1-(6-chloro-4-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Intermediate 35-step 1-Isomer 2, 0.3 g, 1.0 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (3 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.29 g, yield: 81.46%) as an off-white solid. Mass m / z: 350.30 (M+H)+. Intermediate 37: Preparation of (E)-1-(5-chloro-1-ethyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 4-chloro-N1-ethylbenzene-1,2-diamine (2 g, 11.76 mmol, 1.0 eq), L- Lactic acid (1.21 ml, 15.29 mmol, 1.3 eq) and concentrated HCl (8 ml) was stirred and heated at 95oC for 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (1.8 g, yield: 68.44%) as a solid. Mass m / z: 225.12 (M+H)+. Step 2: Synthesis of 1-(5-chloro-1-ethyl-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(5-chloro-1-ethyl-1H-benzo[d]imidazol-2-yl)ethan-1- ol (Step 1, 1.8 g, 8.03 mmol, 1.0 eq) in acetic acid (20 ml) was added potassium dichromate (2.83 g, 9.64 mmol, 1.2 eq). The reaction mixture was heated at 60oC for 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (1.6 g, yield: 89.8 %) as a solid. Mass m / z: 223.21 (M+H)+. Step 3: Synthesis of (E)-1-(5-chloro-1-ethyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(5-chloro-1-ethyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 0.5 g, 2.2 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (5 ml) was heated at 100- 120oC for 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.55 g, yield: 88.0%) as an off-white solid. Mass m / z: 277.92 (M+H)+. Intermediate 38: Preparation of (E)-1-(5,7-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2- yl)-3-(dimethylamino)prop-2-en-1-one: Step 1: Synthesis of 1-(5,7-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)ethan-1-one (Isomer 1) and 1-(4,6-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)ethan-1-one (Isomer 2): To a stirred solution of 1-(5,7-difluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 8-step 2, 3.6 g, 18.3 mmol, 1.0 eq) in N,N-dimethylformamide (36 ml) were added K2CO3 (5.1 g, 36.7 mmol, 2.0 eq) and iodomethane-d3 (1.71 ml, 27.5 mmol, 1.5 eq). The reaction mixture was heated to 90oC for 16 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (1.1 g, yield: 28.0%) and Isomer 2 (1.56 g, yield: 40.0%) as solids. Isomer 1:1H-NMR (500 MHz-DMSO-d6): 7.54 (m, 1H), 7.36 (m, 1H), 2.71 (s, 3H); Mass m / z: 214.12 (M+H)+. Isomer 2:1H-NMR (500 MHz-DMSO-d6): 7.56 (m, 1H), 7.25 (m, 1H), 2.71 (s, 3H); Mass m / z: 213.99 (M+H)+. Step 2: Synthesis of (E)-1-(5,7-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: A mixture of 1-(5,7-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 1-Isomer 1, 0.9 g, 4.2 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (9 ml) washeated at 100-120 oC for 3 hours. TLC indicated starting material was consumed and thedesired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.95 g, yield: 83.3%) as an off-white solid. Mass m / z: 269.03 (M+H)+. Intermediate 39: Preparation of (E)-1-(4,6-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2- yl)-3-(dimethylamino)prop-2-en-1-one: A mixture of 1-(4,6-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 38-step 1-Isomer 2, 1.0 g, 4.7 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (10 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (1.2 g, yield: 94.4 %) as an off-white solid. Mass m / z: 269.03 (M+H)+. Intermediate 40: Preparation of (E)-3-(dimethylamino)-1-(1-(methyl-d3)-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: Step 1: Synthesis of 1-(1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of 1-(1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 1- step 2, 4.0 g, 24.9 mmol, 1.0 eq) in N,N-dimethylformamide (40 ml) were added K2CO3 (6.87 g, 49.8 mmol, 2.0 eq) and iodomethane-d3 (2.32 ml, 37.4 mmol, 1.5 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compound (2.8 g, yield: 63.6%) as a solid. Mass m / z: 178.09 (M+H)+. Step 2: Synthesis of (E)-3-(dimethylamino)-1-(1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)prop- 2-en-1-one: A mixture of 1-(1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 1, 2.6 g, 14.6 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (26 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (2.8 g, yield: 82.3%) as an off-white solid. Mass m / z: 233.21 (M+H)+. Intermediate 41: Preparation of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitro-2- (2,2,2-trifluoroethoxy)phenyl)guanidine: Step 1: Synthesis of 1-fluoro-2,4-dinitro-5-(2,2,2-trifluoroethoxy)benzene: To a stirred solution of 1,5-difluoro-2,4-dinitrobenzene (5.0 g, 24.4 mmol, 1.0 eq) in N,N-dimethylformamide (50 ml) were added K2CO3 (6.76 g, 48.9 mmol, 2.0 eq) and 2,2,2- trifluoroethan-1-ol (1.75 ml, 24.4 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 10-30% ethyl acetate in n-hexane gradient to obtain the title compound (5.41 g, yield: 78.0%). Mass m / z: 282.71 (M-H)+. Step 2: Synthesis of 4-fluoro-5-nitro-2-(2,2,2-trifluoroethoxy)aniline: To a stirred solution of 1-fluoro-2,4-dinitro-5-(2,2,2-trifluoroethoxy)benzene (Step 1, 6.5 g, 22.8 mmol, 1.0 eq) in THF (65 ml) and water (13 ml) was added Na2S2O4 (19.9 g, 114.4 mmol, 5.0 eq) and stirred for 10 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (250 ml) and washed with water (200 ml) and brine (100 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 30-40% ethyl acetate in n-hexane gradient to obtain the title compound (3.2 g, yield: 55.0%). Mass m / z: 255.12 (M+H)+. Step 3: Synthesis of 1-(4-fluoro-5-nitro-2-(2,2,2-trifluoroethoxy)phenyl)guanidine: To a stirred solution of 4-fluoro-5-nitro-2-(2,2,2-trifluoroethoxy)aniline (Step 2, 1.0 g, 3.9 mmol, 1.0 eq) in ethanol (6 ml) and water (1.2 ml) were added concentrated HCl (1 ml) and cyanamide solution (3.5 ml, 50% aqueous solution). The reaction mixture was heated at 75oC for 24 hours. The reaction mixture was cooled to room temperature, ice water was added and stirred for 30 minutes. The resulting solution was filtered and the filtrate was adjusted to pH >12 by using aqueous 25% NaOH solution and the obtained solid was collected by filtration and washed with water and dried under vacuum to give title compound (1.1 g, yield: 94.8%). Mass m / z: 296.93 (M+H)+. Step 4: Synthesis of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-5-nitro-2-(2,2,2- trifluoroethoxy)phenyl)guanidine: To a stirred solution of 1-(4-fluoro-5-nitro-2-(2,2,2- trifluoroethoxy)phenyl)guanidine (Step 3, 1.5 g, 5.0 mmol, 1.0 eq) in N,N- dimethylformamide (15 ml) were added K2CO3 (2.1 g, 15.0 mmol, 3.0 eq) and N1,N1,N2- trimethylethane-1,2-diamine (0.65 ml, 5.0 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 379.20 (M+H)+. Intermediate 42: Preparation of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-(2- methoxyethoxy)-5-nitrophenyl)guanidine: Step 1: Synthesis of 1-fluoro-5-(2-methoxyethoxy)-2,4-dinitrobenzene: To a stirred solution of 1,5-difluoro-2,4-dinitrobenzene (5.0 g, 24.4 mmol, 1.0 eq) in 1,4-dioxane (50 ml) were added K2CO3 (6.76 g, 48.9 mmol, 2.0 eq) and 2-methoxyethan- 1-ol (2.89 ml, 36.7 mmol, 1.5 eq). The reaction mixture was stirred at rt for 12 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 10-30% ethyl acetate in n-hexane gradient to obtain the title compound (4.6 g, yield: 73.0%). Mass m / z: 261.21 (M+H)+. Step 2: Synthesis of 4-fluoro-2-(2-methoxyethoxy)-5-nitroaniline: To a stirred solution of 1-fluoro-5-(2-methoxyethoxy)-2,4-dinitrobenzene (Step 1, 4.6 g, 17.6 mmol, 1.0 eq) in THF (50 ml) and water (10 ml) was added Na2S2O4 (18.55 g, 106.1 mmol, 6.0 eq) and stirred for 10 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (250 ml) and washed with water (200 ml) and brine (100 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 30-40% ethyl acetate in n-hexane gradient to obtain the title compound (1.8 g, yield: 45.0%). Mass m / z: 231.23 (M+H)+. Step 3: Synthesis of 1-(4-fluoro-2-(2-methoxyethoxy)-5-nitrophenyl)guanidine: To a stirred solution of 4-fluoro-2-(2-methoxyethoxy)-5-nitroaniline (Step 2, 0.9 g, 3.9 mmol, 1.0 eq) in ethanol (6 ml) and water (1.1 ml) were added concentrated HCl (1 ml) and cyanamide solution (2.7 ml, 50% aqueous solution). The reaction mixture was heated at 75oC for 24 hours. The reaction mixture was cooled to room temperature; ice water was added and stirred for 30 minutes. The resulting solution was filtered, and the filtrate was adjusted to pH >12 by using aqueous 25% NaOH solution and the obtained solid was collected by filtration and washed with water and dried under vacuum to give title compound (0.7 g, yield: 66.0%). Mass m / z: 273.31 (M+H)+. Step 4: Synthesis of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-(2-methoxyethoxy)-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-(2-methoxyethoxy)-5-nitrophenyl)guanidine (Step 3, 0.7 g, 2.5 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.06 g, 7.5 mmol, 3.0 eq) and N1,N1,N2-trimethylethane-1,2-diamine (0.33 ml, 2.5 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 355.34 (M+H)+. Intermediate 43: Preparation of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-(methoxy- d3)-5-nitrophenyl)guanidine: Step 1: Synthesis of 1-fluoro-5-(methoxy-d3)-2,4-dinitrobenzene: To a stirred solution of 1,5-difluoro-2,4-dinitrobenzene (4.0 g, 19.6 mmol, 1.0 eq) in N,N-dimethylformamide (50 ml) were added K2CO3 (5.41 g, 39.2 mmol, 2.0 eq) and methan-d3-ol-d (0.89 ml, 19.6 mmol, 1.0 eq). The reaction mixture was stirred at RT for 12 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 10- 30% ethyl acetate in n-hexane gradient to obtain the title compound (1.7 g, yield: 40%). Mass m / z: 220.12 (M+H)+. Step 2: Synthesis of 4-fluoro-2-(methoxy-d3)-5-nitroaniline: To a stirred solution of 1-fluoro-5-(methoxy-d3)-2,4-dinitrobenzene (Step 1, 1.4 g, 6.4 mmol, 1.0 eq) in THF (15 ml) and water (4 ml) was added Na2S2O4 (9.02 g, 51.8 mmol, 8.0 eq) and stirred for 10 h. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (150 ml) and washed with water (100 ml) and brine (100 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 30-40% ethyl acetate in n-hexane gradient to obtain the title compound (0.46 g, yield: 38.3%). Mass m / z: 190.21 (M+H)+. Step 3: Synthesis of 1-(4-fluoro-2-(methoxy-d3)-5-nitrophenyl)guanidine: To a stirred solution of 4-fluoro-2-(methoxy-d3)-5-nitroaniline (Step 2, 0.46 g, 2.4 mmol, 1.0 eq) in ethanol (3 ml) and water (0.6 ml) were added concentrated HCl (0.5 ml) and cyanamide solution (1.4 ml, 50% aqueous solution). The reaction mixture was heated at 75oC for 24 hours. The reaction mixture was cooled to room temperature; ice water was added and stirred for 30 minutes. The resulting solution was filtered, and the filtrate was adjusted to pH >12 by using aqueous 25% NaOH solution and the obtained solid was collected by filtration and washed with water and dried under vacuum to give title compound (0.4 g, yield: 52.0%). Mass m / z: 232.32 (M+H)+. Step 4: Synthesis of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-(methoxy-d3)-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-(methoxy-d3)-5-nitrophenyl)guanidine (Step 3, 0.4 g, 1.7 mmol, 1.0 eq) in N,N-dimethylformamide (6 ml) were added K2CO3 (0.725 g, 5.2 mmol, 3.0 eq) and N1,N1,N2-trimethylethane-1,2-diamine (0.23 ml, 1.7 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. Mass m / z: 314.42 (M+H)+. Intermediate 44: Preparation of (E)-1-(5-chloro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one (Isomer 1) and (E)-1-(6-chloro- 1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one (Isomer 2): Step 1: Synthesis of (S)-1-(5-chloro-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of 4-chlorobenzene-1,2-diamine (6.0 g, 42.2 mmol, 1.0 eq), L-Lactic acid (4.2 ml, 54.9 mmol, 1.3 eq) and concentrated HCl (12 ml) was stirred and heated at 95oC for 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (7.5 g, yield: 90.5%) as a solid. Mass m / z: 197.36 (M+H)+. Step 2: Synthesis of 1-(5-chloro-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(5-chloro-1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 1, 7.5 g, 38.2 mmol, 1.0 eq) in acetic acid (75 ml) was added potassium dichromate (13.5 g, 45.9 mmol, 1.2 eq). The reaction mixture was heated at 60oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (300 ml) and washed with water (200 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (6.2 g, yield: 83.5%) as a solid. Mass m / z: 195.24 (M+H)+. Step 3: Synthesis of 1-(5-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1- one and 1-(6-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of 1-(5-chloro-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2,3.8 g, 19.5 mmol, 1.0 eq) in N,N-dimethylformamide (40 ml) were added K2CO3 (8.1 g, 58.7mmol, 3.0 eq) and 2,2,2-trifluoroethyl 4-methylbenzenesulfonate (5.96 g, 23.5 mmol, 1.2 eq). The reaction mixture was heated to 90oC for 18 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds (3.2 g, yield: 59.2%) as a mixture of solid. Mass m / z: 277.29 (M+H)+. Step 4: Synthesis of (E)-1-(5-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Isomer 1) and (E)-1-(6-chloro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one (Isomer 2): an A mixture of 1-(5-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1- one and 1-(6-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 3, 1.5 g, 5.4 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (15 ml) was heated at 100- 120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated 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 Isomer 1 (0.8 g, yield: 44.6%) and Isomer 2 (0.5 g, yield: 28.0%) as pale brown solids. Isomer 1:1H-NMR (500 MHz-DMSO-d6): 7.97 (d, J = 2.0 Hz, 1H), 7.88 (m, 1H), 7.82 (d, J = 8.5 Hz, 1H), 7.38 (dd, J = 2.0 Hz, 8.5 Hz, 1H), 6.24 (m, 1H), 5.86 (m, 2H), 3.22 (s, 3H), 2.96 (s, 3H); Mass m / z: 332.27 (M+H)+. Isomer 2:1H-NMR (500 MHz-DMSO-d6): 7.93 (d, J = 8.5 Hz, 1H), 7.86 (m, 1H), 7.84 (d, J = 2.0 Hz, 1H), 7.40 (dd, J = 2.0 Hz, 8.5 Hz, 1H), 6.22 (m, 1H), 5.90 (m, 2H), 3.21 (s, 3H), 2.98 (s, 3H); Mass m / z: 332.31 (M+H)+. Intermediate 45: Preparation of (E)-3-(dimethylamino)-1-(5-fluoro-1-(2,2,2-trifluoroethyl)- 1H-benzo[d]imidazol-2-yl)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of 4-fluorobenzene-1,2-diamine (5 g, 23.1 mmol, 1.0 eq), L-Lactic acid (3.44 ml, 46.2 mmol, 2.0 eq) and concentrated HCl (20 ml) was stirred and heated at 95oC for 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (4.08 g, yield: 98.3%) as a solid. Mass m / z: 181.12 (M+H)+. Step 2: Synthesis of 1-(5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 1, 4.08 g, 22.6 mmol, 1.0 eq) in acetic acid (40 ml) was added potassium dichromate (7.99 g, 27.1 mmol, 1.2 eq). The reaction mixture was heated at 60oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (100 ml) and washed with water (100 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (3.7 g, yield: 91.8%) as a solid. Mass m / z: 179.13 (M+H)+. Step 3: Synthesis of 1-(5-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1- one (Isomer 1) and 1-(6-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan-1- one (Isomer 2): To a stirred solution of 1-(5-fluoro-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 3.7 g, 20.7 mmol, 1.0 eq) in N,N-dimethylformamide (37 ml) were added K2CO3 (8.6 g, 62.3 mmol, 3.0 eq) and 2,2,2-trifluoroethyl 4-methylbenzenesulfonate (5.8 g, 22.8 mmol, 1.1 eq). The reaction mixture was heated to 90oC for 16 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (0.9 g, yield: 16.0%) and Isomer 2 (0.7 g, yield: 12.4%) as solids. Isomer 1: Mass m / z: 261.12 (M+H)+. Isomer 2: Mass m / z: 261.15 (M+H)+. Step 4: Synthesis of (E)-3-(dimethylamino)-1-(5-fluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: A mixture of 1-(5-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan- 1-one (Step 3-Isomer 1, 0.9 g, 3.4 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (10 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.93 g, yield: 86.0%) as an off- white solid. Mass m / z: 316.21 (M+H)+. Intermediate 46: Preparation of (E)-3-(dimethylamino)-1-(6-fluoro-1-(2,2,2-trifluoroethyl)- 1H-benzo[d]imidazol-2-yl)prop-2-en-1-one: A mixture of 1-(6-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan- 1-one (Intermediate 45-step 3-Isomer 2, 0.7 g, 2.7 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (10 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.6 g, yield: 70.7%) as an off-white solid. Mass m / z: 316.19 (M+H)+. Intermediate 47: Preparation of 1-(4-(4-(dimethylamino)piperidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.6 g, 2.6 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) were added K2CO3 (1.09 g, 7.8 mmol, 3.0 eq) and N,N-dimethylpiperidin-4-amine (0.3 ml, 2.6 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 337.33 (M+H)+. Intermediate 48: Preparation of 1-(2-methoxy-4-(4-methylpiperazin-1-yl)-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.6 g, 2.63 mmol, 1.0 eq) in N,N-dimethylformamide (6 ml) were added K2CO3 (1.0 g, 7.89 mmol, 3.0 eq) and 1-methylpiperazine (0.29 ml, 2.63 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, whichwas used as such for next step without further purification. ES-MS: m / z 309.16 (M+H)+.Intermediate 49: Preparation of 1-(4-(3-(dimethylamino)azetidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 0.6 g, 2.63 mmol, 1.0 eq) in N,N-dimethylformamide (6 ml) were added K2CO3 (1.0 g, 7.89 mmol, 3.0 eq) and N,N-dimethylazetidin-3-amine hydrogen chloride (0.357 g, 2.63 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 12 hours. The reaction mixture was concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification.ES-MS: m / z 309.16 (M+H)+. Intermediate 50: Preparation of (E)-3-(dimethylamino)-1-(5-methoxy-1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one: Step 1: Synthesis of (S)-1-(5-methoxy-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of 4-methoxybenzene-1,2-diamine (10.0 g, 72.4 mmol, 1.0 eq) and L- Lactic acid (10.78 ml, 144.8 mmol, 2.0 eq) in toluene (100 ml) was stirred and heated at 110oC for 18 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (4.4 g, yield: 31.6%) as a solid. Mass m / z: 193.21 (M+H)+. Step 2: Synthesis of 1-(5-methoxy-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(5-methoxy-1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 1, 4.4 g, 22.9 mmol, 1.0 eq) in acetic acid (45 ml) was added potassium dichromate (8.08 g, 27.4 mmol, 1.2 eq). The reaction mixture was heated at 60oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (400 ml) and washed with water (200 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (4.0 g, yield: 91.9%) as a solid. Mass m / z: 191.24 (M+H)+. Step 3: Synthesis of 1-(5-methoxy-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan- 1-one (Isomer 1) and 1-(6-methoxy-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)ethan- 1-one (Isomer 2): and To a stirred solution of 1-(5-methoxy-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 2, 2.7 g, 14.2 mmol, 1.0 eq) in N,N-dimethylformamide (30 ml) were added K2CO3 (5.8 g, 42.6 mmol, 3.0 eq) and 2,2,2-trifluoroethyl 4-methylbenzenesulfonate (3.6 g, 14.2 mmol, 1.0 eq). The reaction mixture was heated to 90oC for 24 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (0.84 g, yield: 22.0%) and Isomer 2 (0.695 g, yield: 18.0%) as solids. Isomer 1: Mass m / z: 273.13 (M+H)+. Isomer 2: Mass m / z: 273.21 (M+H)+. Step 4: Synthesis of (E)-3-(dimethylamino)-1-(5-methoxy-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: A mixture of 1-(5-methoxy-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Step 3-Isomer 1, 0.6 g, 2.2 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (6 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.55 g, yield: 76.2%) as an off-white solid. Mass m / z: 328.31 (M+H)+. Intermediate 51: Preparation of (E)-3-(dimethylamino)-1-(6-methoxy-1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one: A mixture of 1-(6-methoxy-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)ethan-1-one (Intermediate 50-step 3-Isomer 2, 0.7 g, 2.7 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (7 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.68 g, yield: 81.2%) as an off-white solid. Mass m / z: 328.34 (M+H)+. Intermediate 52: Preparation of (E)-3-(dimethylamino)-1-(5-methoxy-1-methyl-1H- benzo[d]imidazol-2-yl)prop-2-en-1-one: To a stirred solution of 1-(5-methoxy-1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 50-step 2, 1.8 g, 9.4 mmol, 1.0 eq) in N,N-dimethylformamide (20 ml) were added K2CO3(3.92 g, 28.42 mmol, 3.0 eq) and iodomethane (1.77 ml, 28.42 mmol, 3.0 eq). The reaction mixture was heated to 90oC for 24 hours. The reaction mixture was diluted with water and extracted with EtOAc. 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 20-40% ethyl acetate in n-hexane gradient to obtain the title compounds Isomer 1 (0.617 g, yield: 32.0%) and Isomer 2 (0.231 g, yield: 12.0%) as solids. Isomer 1: Mass m / z: 205.35 (M+H)+. Isomer 2: Mass m / z: 205.27 (M+H)+. Step 2: Synthesis of (E)-3-(dimethylamino)-1-(5-methoxy-1-methyl-1H-benzo[d]imidazol-2- yl)prop-2-en-1-one: A mixture of 1-(5-methoxy-1-methyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 1-Isomer 1, 0.6 g, 2.9 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (6 ml) was heated at 100-120oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (0.4 g, yield: 52.5%) as an off-white solid. Mass m / z: 260.26 (M+H)+. Intermediate 53: Preparation of 1-(4-(2-(dimethylamino)ethoxy)-2-methoxy-5- nitrophenyl)guanidine: To a stirred solution of 1-(4-fluoro-2-methoxy-5-nitrophenyl)guanidine (Intermediate 18-step 1, 1 g, 4.38 mmol, 1.0 eq) in N,N-dimethylformamide (10 ml) at 0°C, were added 2-(dimethylamino)ethan-1-ol (0.48 ml, 4.82 mmol, 1.1 eq) and NaH (0.344 g, 60% dispersion in mineral oil, 8.77 mmol, 2.0 eq). The reaction mixture was stirred at rt for 12 hours. The reaction mixture was quenched with MeOH (10 ml) at 0 °C and concentrated under reduced pressure to obtain the title compound as a dark thick oil, which was used as such for next step without further purification. ES-MS: m / z 298.09 (M+H)+. Intermediate 54: Preparation of (E)-1-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one: Step 1: Synthesis of N-cyclobutyl-2-nitroaniline: To a stirred solution of 1-fluoro-2-nitrobenzene (3.0 g, 21.27 mmol, 1.0 eq) in N,N- dimethylformamide (30 ml) were added K2CO3 (5.8 g, 42.54 mmol, 3.0 eq) and cyclobutanamine (4.5 ml, 53.18 mmol, 2.5 eq). The reaction mixture was heated to 90oC for 12 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with water and extracted with EtOAc. 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 20- 30% ethyl acetate in n-hexane gradient to obtain the title compounds (4.0 g, yield: 98.0%) asa liquid. Mass m / z: 193.23 (M+H)+.Step 2: Synthesis of N1-cyclobutylbenzene-1,2-diamine: To a stirred solution of N-cyclobutyl-2-nitroaniline (Step 1, 4.0 g, 20.83 mmol, 1.0 eq) in ethanol (16 ml) at 0°C, were added Iron (11.6 g, 208.3 mmol, 10.0 eq), NH4Cl (16.7 g, 312.49 mmol, 15.0 eq) and water (4.0 ml). The reaction mixture was heated to 70oC for 4 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 and the obtained residue was basified with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (2.6 g, yield: 78.0%), which was used as such for next step without further purification. Mass m / z: 163.25 (M+H)+. Step 3: Synthesis of (S)-1-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)ethan-1-ol: A mixture of N1-cyclobutylbenzene-1,2-diamine (Step 2, 2.6 g, 16.04 mmol, 1.0 eq) and L-Lactic acid (2.3 ml, 32.09 mmol, 2.0 eq) and concentrated HCl (10 ml) was stirred and heated at 95oC for 16 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was neutralized with saturated sodium bicarbonate solution and the obtained solid was collected by filtration. The solid was taken into RB flask, water was added and heated to reflux for 30 minutes. The reaction mixture was allowed to reach to room temperature, the precipitate formed was collected by filtration and dried under vacuum to obtain the title compound (3.0 g, yield: 88.0%) as a solid. Mass m / z: 217.25 (M+H)+. Step 4: Synthesis of 1-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of (S)-1-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)ethan-1-ol (Step 3, 4.4 g, 20.36 mmol, 1.0 eq) in acetic acid (45 ml) was added potassium dichromate (7.18 g, 24.93 mmol, 1.2 eq). The reaction mixture was heated at 60oC for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with ethyl acetate (400 ml) and washed with water (200 ml). The organic layer was separated, washed with saturated sodium bicarbonate solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to give title compound (2.9 g, yield: 67.0%) as a solid. Mass m / z: 215.32 (M+H)+. Step 5: Synthesis of (E)-1-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop- 2-en-1-one: A mixture of 1-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 4, 2.9 g, 13.54 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (30 ml) was heated at 100- 120oC for 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (2.0 g, yield: 54.0%) as an off-white solid. Mass m / z: 270.23 (M+H)+. Intermediate 55: Preparation of (E)-3-(dimethylamino)-1-(1-ethyl-1H-benzo[d]imidazol-2- yl)prop-2-en-1-one: Step 1: Synthesis of 1-(1-ethyl-1H-benzo[d]imidazol-2-yl)ethan-1-one: To a stirred solution of 1-(1H-benzo[d]imidazol-2-yl)ethan-1-one (Intermediate 1- step 2, 2.0 g, 12.5 mmol, 1.0 eq) in DMF (20 ml) were added K2CO3 (5.1 g, 37.5 mmol, 3.0 eq) and iodoethane (2.0 ml, 25.0 mmol, 2.0 eq). The reaction mixture was heated to 90oC for 18 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with MTBE (100 ml) and washed with water (50 ml) and brine solution (30 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 30-40% EtOAc in n-hexane gradient to obtain the title compound (2.0 g, yield: 85.0%) as a solid. Mass m / z: 189.10 (M+H)+. Step 2: Synthesis of (E)-3-(dimethylamino)-1-(1-ethyl-1H-benzo[d]imidazol-2-yl)prop-2-en- 1-one: A mixture of 1-(1-ethyl-1H-benzo[d]imidazol-2-yl)ethan-1-one (Step 1, 2.0 g, 10.63 mmol, 1.0 eq) and dimethylformamide dimethyl acetal (20 ml) was heated at 100-120oC for 2 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure. The crude compound was recrystallized with toluene: hexane (1:1). The solid was filtered and dried under vacuum to obtain the title compound (2.0 g, yield: 77.0%) as an off-white solid. Mass m / z: 244.07 (M+H)+. EXAMPLES Example 1: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4- (1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 13.59 g, 43.85 mmol, 1eq)in n-butanol (200 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 5.9 g, 25.776 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (6.0 g, yield: 39.2% (for two steps)) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 8.70 (s, 1H), 8.58 (d, J = 5.0 Hz, 1H), 8.30 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 5.0 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 6.82 (s, 1H), 4.15 (s, 3H), 3.93 (s, 3H), 3.28 (m, 4H), 2.85 (s, 3H), 2.17 (s, 6H); Mass m / z: 477.48 (M+H)+. Step 2: Synthesis of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4-triamine: To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine (Step 1, 6.0 g, 12.59 mmol, 1.0 eq) in methanol (60 ml) and ethyl acetate (60 ml) was added 10% Pd / C (0.8 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (200 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (4.5 g) was used as such for next step without further purification. Step 3: Synthesis of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4-triamine (Step 2, 4.5 g, 10.07 mmol, 1.0 eq) in DCM (50 ml) at 0 ºC, were added N,N-Diisopropylethylamine (3.5 ml, 20.156 mmol, 2.0 eq) and acryloyl chloride (0.82 ml, 10.07 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 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 (100 ml) and brine solution (100 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 (2.4 g, yield: 38.0% (for two steps)) as a yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.11 (s, 1H), 8.65 (s, 1H), 8.57 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 7.01 (s, 1H), 6.38 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.19 (dd, J = 1.5 Hz, 17.0 Hz, 1H), 5.73 (dd, J = 1.5 Hz, 10.0 Hz, 1H), 4.08 (s, 3H), 3.80 (s, 3H), 2.88 (t, J = 6.0 Hz, 2H), 2.72 (s, 3H), 2.31 (t, J = 6.0 Hz, 2H), 2.21 (s, 6H); Mass m / z: 501.07 (M+H)+. Example 2: Preparation of 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)propanamide: To a stirred solution of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide (Example 1, 0.06 g, 0.119 mmol) in 1,4-Dioxane (3 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (2.0 ml). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (30 ml) and washed with saturated NaHCO3 solution (10 ml) and brine solution (20 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 (0.022 g, yield: 34%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.96 (s, 1H), 8.61 (s, 1H), 8.56 (d, J = 5.0 Hz, 1H), 8.48 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.58 (m, 2H), 7.35 (t, J = 8.0 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 6.99 (s, 1H), 4.09 (s, 3H), 3.87 (t, J = 6.0 Hz, 2H), 3.80 (s, 3H), 2.91 (s, 2H), 2.82 (t, J = 6.0 Hz, 2H), 2.71 (s, 3H), 2.25 (m, 2H), 2.27 (s, 6H); Mass m / z: 537.42 (M+H)+. Example 3: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4- (1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propionamide: To a stirred solution of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide (Example 1, 0.11 g, 0.219 mmol, 1.0 eq) in ethyl acetate (5 ml) was added 10% Pd / C (0.05 g, 50% wet). The reaction mixture was stirred at room temperature under hydrogen atmosphere for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with ethyl acetate (30 ml). The filtrate was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 0-2% methanol in dichloromethane gradient to obtain the title compound (0.086 g, yield: 78%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.78 (s, 1H), 8.61 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 8.48 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 6.98 (s, 1H), 4.08 (s, 3H), 3.78 (s, 3H), 2.88 (t, J = 5.5 Hz, 2H), 2.70 (s, 3H), 2.31 (m, 4H), 2.22 (s, 6H), 1.09 (t, J = 7.5 Hz, 3H); Mass m / z: 503.45 (M+H)+. Example 4: Preparation of N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-morpholinophenyl)acrylamide: Step 1: Synthesis of N-(2-methoxy-4-morpholino-5-nitrophenyl)-4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-amine: To a stirred solution of 1-(2-methoxy-4-morpholino-5-nitrophenyl)guanidine (Intermediate 19, 2.58 g, 8.77 mmol, 1.0 eq) in n-butanol (50 ml) was added (E)-3- (dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 1.21 g, 5.263 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.1 g, yield: 27.3% (for two steps)) as an off-white solid. Step 2: Synthesis of 6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- 4-morpholinobenzene-1,3-diamine: To a stirred solution of N-(2-methoxy-4-morpholino-5-nitrophenyl)-4-(1-methyl- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine (Step 1, 1.1 g, 2.383 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.2 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.9 g) was used as such for next step without further purification. Step 3: Synthesis of N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of 6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-4-morpholinobenzene-1,3-diamine (Step 2, 0.9 g, 2.085 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.72 ml, 4.17 mmol, 2.0 eq) and acryloyl chloride (0.17 ml, 2.085 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.32 g, yield: 27.82% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.09 (s, 1H), 8.64 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 8.29 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 6.89 (s, 1H), 6.65 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.19 (d, J = 17.0 Hz, 1H), 5.72 (d, J = 10.0 Hz, 1H), 4.09 (s, 3H), 3.80 (m, 7H), 2.87 (m, 4H); Mass m / z: 486.0 (M+H)+. Example 5: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4- (1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acetamide: To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4-triamine (Example 1- step 2, 0.22 g, 0.43 mmol, 1.0 eq) in DCM (5 ml) at 0 ºC, were added triethylamine (0.2 ml, 1.4 mmol, 3.0 eq) and acetic anhydride (0.055 ml, 0.6 mmol, 1.2 eq). The reaction mixture was allowed to room temperature and stirred for about 4 hours. 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 (20 ml) and brine solution (20 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 (0.125 g, yield: 52.0%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 9.9 (brs, 1H), 8.62 (s, 1H), 8.54 (m, 1H), 8.36 (brs, 1H), 7.73 (m, 1H), 7.63 (m, 1H), 7.57 (m, 1H), 7.32 (m, 2H), 6.97 (s, 1H), 4.08 (s, 3H), 3.79 (s, 3H), 2.92 (m, 2H), 2.69 (s, 3H), 2.52 (m, 2H), 2.27 (s, 6H), 2.05 (s, 3H); Mass m / z: 489.37 (M+H)+. Example 6: Preparation of N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: Step 1: Synthesis of 1-(5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-nitrophenyl)piperidin-4-ol: To a stirred solution of 1-(4-(4-hydroxypiperidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 20, 1.35 g, 4.38 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.6 g, 2.629 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.8 g, yield: 38.5% (for two steps)) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 8.74 (s, 1H), 8.60 (d, J = 5.0 Hz, 1H), 8.45 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 5.0 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 6.81 (s, 1H), 4.72 (d, J = 4.5 Hz, 1H), 4.16 (s, 3H), 3.95 (s, 3H), 3.68 (m, 1H), 3.23 (m, 2H), 2.91 (m, 2H), 1.87 (m, 2H), 1.58 (m, 2H). Step 2: Synthesis of 1-(2-amino-5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)piperidin-4-ol: To a stirred solution of 1-(5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-nitrophenyl)piperidin-4-ol (Step 1, 0.8 g, 1.682 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (30 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.6 g) was used as such for next step without further purification. Step 3: Synthesis of N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- To a stirred solution of 1-(2-amino-5-methoxy-4-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)piperidin-4-ol (Step 2, 0.6 g, 1.346 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.46 ml, 2.693 mmol, 2.0 eq) and acryloyl chloride (0.11 ml, 1.346 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.22 g, yield: 26.2% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 8.98 (s, 1H), 8.62 (s, 1H), 8.53 (d, J = 5.0 Hz, 1H), 8.25 (s, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 6.85 (s, 1H), 6.62 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.18 (d, J = 17.0 Hz, 1H), 5.71 (d, J = 10.0 Hz, 1H), 4.70 (d, J = 3.5 Hz, 1H), 4.08 (s, 3H), 3.80 (s, 3H), 3.64 (m, 1H), 2.99 (m, 2H), 2.70 (m, 2H), 1.88 (m, 2H), 1.66 (m, 2H); Mass m / z: 500.38 (M+H)+. Example 7: Preparation of 3-chloro-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-morpholinophenyl)propanamide: To a stirred solution of N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-morpholinophenyl)acrylamide (Example 4, 0.08 g, 0.164 mmol) in 1,4-Dioxane (3 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (2.0 ml). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (30 ml) and washed with saturated NaHCO3 solution (10 ml) and brine solution (20 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 (0.032 g, yield: 37%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.05 (s, 1H), 8.60 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 8.15 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 5.0 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 6.85 (s, 1H), 4.10 (s, 3H), 3.87 (t, J = 6.0 Hz, 2H), 3.82 (s, 3H), 3.80 (m, 4H), 2.89 (m, 6H); Mass m / z: 522.16 (M+H)+. Example 8: Preparation of 3-chloro-N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propanamide: To a stirred solution of N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1-methyl- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide (Example 6, 0.02 g, 0.040 mmol) in 1,4-Dioxane (2 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (1.0 ml). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (20 ml) and washed with saturated NaHCO3 solution (5 ml) and brine solution (10 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 (0.0036 g, yield: 16.8%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 8.95 (s, 1H), 8.59 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.16 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 6.83 (s, 1H), 4.69 (d, J = 4.0 Hz, 1H), 4.10 (s, 3H), 3.87 (t, J = 6.0 Hz, 2H), 3.80 (s, 3H), 3.64 (m, 1H), 3.02 (m, 2H), 2.89 (t, J = 6.0 Hz, 2H), 2.70 (m, 2H), 1.88 (m, 2H), 1.68 (m, 2H); Mass m / z: 536.24 (M+H)+. Example 9: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(2-(dimethylamino)ethyl)-N4-(4-(5-fluoro-1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4-diamine: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.0 g, 3.2 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1- one (Intermediate 12, 0.478 g, 1.9 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.95 g, yield: 59.74%) as an off-white solid. Mass m / z: 495.00 (M+H)+. Step 2: Synthesis of N1-(2-(dimethylamino)ethyl)-N4-(4-(5-fluoro-1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methylbenzene-1,2,4-triamine: To a stirred solution of N1-(2-(dimethylamino)ethyl)-N4-(4-(5-fluoro-1-methyl- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4- diamine (Step 1, 0.95 g, 1.9 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.8 g) was used as such for next step without further purification. Mass m / z: 465.16 (M+H)+. Step 3: Synthesis of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1-methyl- To a stirred solution of N1-(2-(dimethylamino)ethyl)-N4-(4-(5-fluoro-1-methyl- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (Step 2, 0.8 g, 1.72 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.636 ml, 3.4 mmol, 2.0 eq) and acryloyl chloride (0.14 ml, 1.7 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.2 g, yield: 22.39%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.11 (s, 1H), 8.68 (s, 1H), 8.56 (m, 2H), 7.65 (m, 1H), 7.55 (m, 2H), 7.24 (m, 1H), 7.01 (s, 1H), 6.38 (m, 1H), 6.21 (m, 1H), 5.73 (m, 1H), 4.08 (s, 3H), 3.79 (s, 3H), 2.88 (m, 2H), 2.72 (s, 3H), 2.31 (m, 2H), 2.21 (s, 6H); Mass m / z: 519.15 (M+H)+. Example 10: Preparation of (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-5-((4-(5-fluoro-1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide: Step 1: Synthesis of (S)-N-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-methoxy-5-nitrophenyl)- 4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine: To a stirred solution of (S)-1-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 26, 1.129 g, 3.5 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1- one (Intermediate 12, 0.519 g, 2.10 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.0 g, yield: 56.4%) as an off-white solid. Mass m / z: 507.05 (M+H)+. Step 2: Synthesis of (S)-4-(3-(dimethylamino)pyrrolidin-1-yl)-N1-(4-(5-fluoro-1-methyl-1H- To a stirred solution of (S)-N-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)-4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine (Step 1, 1.0 g, 1.9 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.8 g) was used as such for next step without further purification. Mass m / z: 477.14 (M+H)+. Step 3: Synthesis of (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-5-((4-(5-fluoro-1-methyl- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide: To a stirred solution of (S)-4-(3-(dimethylamino)pyrrolidin-1-yl)-N1-(4-(5-fluoro- 1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-6-methoxybenzene-1,3-diamine (Step 2, 1.2 g, 2.5 mmol, 1.0 eq) in DCM (15 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.93 ml, 5.0 mmol, 2.0 eq) and acryloyl chloride (0.203 ml, 2.5 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.38 g, yield: 28.4%) as a pale brown solid.1H-NMR (500 MHz-DMSO-d6): 9.35 (s, 1H), 8.52 (m, 2H), 7.65 (m, 1H), 7.55 (m, 3H), 7.25 (m, 1H), 6.49 (m, 2H), 6.18 (m, 1H), 5.68 (m, 1H), 4.10 (s, 3H), 3.80 (s, 3H), 3.38 (m, 1H), 3.23 (m, 3H), 2.69 (m, 1H), 2.16 (s, 6H), 2.07 (m, 1H), 1.72 (m, 1H); Mass m / z: 531.09 (M+H)+. Example 11: Preparation of (S)-N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-4-methoxy-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1- Step 1: Synthesis of (S)-4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-N-(2-methoxy-4-(3- (4-methylpiperazin-1-yl)pyrrolidin-1-yl)-5-nitrophenyl)pyrimidin-2-amine: To a stirred solution of (S)-1-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin- 1-yl)-5-nitrophenyl)guanidine (Intermediate 27, 1.4 g, 3.7 mmol, 1.0 eq) in n-butanol (30 ml) was added (E)-3-(dimethylamino)-1-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)prop-2- en-1-one (Intermediate 12, 0.594 g, 2.2 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.5 g, yield: 72.11%) as an off-white solid. Mass m / z: 562.15 (M+H)+. Step 2: Synthesis of (S)-N1-(4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- 6-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)benzene-1,3-diamine: To a stirred solution of (S)-4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-N-(2- methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)-5-nitrophenyl)pyrimidin-2-amine (Step 1, 1.5 g, 2.6 mmol, 1.0 eq) in methanol (15 ml) and ethyl acetate (15 ml) was added 10% Pd / C (0.12 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (1.2 g) was used as such for next step without further purification. Step 3: Synthesis of (S)-N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of (S)-N1-(4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-6-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)benzene-1,3- diamine (Step 2, 1.6 g, 3.0 mmol, 1.0 eq) in DCM (20 ml) at 0 ºC, were added N,N- Diisopropylethylamine (1.11 ml, 6.0 mmol, 2.0 eq) and acryloyl chloride (0.24 ml, 3.0 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (2.4 g, yield: 38.0% (for two steps)) as a pale orange solid.1H-NMR (500 MHz- DMSO-d6): 9.34 (s, 1H), 8.54 (m, 2H), 7.65 (m, 1H), 7.53 (m, 3H), 7.25 (m, 1H), 6.49 (m, 2H), 6.15 (m, 1H), 5.68 (m, 1H), 4.10 (s, 3H), 3.80 (s, 3H), 3.39 (m, 1H), 3.26 (m, 1H), 3.16 (m, 2H), 2.79 (m, 1H), 2.33 (m, 8H), 2.14 (s, 3H), 2.11 (m, 1H), 1.71 (m, 1H); Mass m / z: 586.15 (M+H)+. Example 12: Preparation of N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-4-methoxy-2-(4-(4-methylpiperazin-1-yl)piperidin-1- yl)phenyl)acrylamide: Step 1: Synthesis of 4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-N-(2-methoxy-4-(4-(4- To a stirred solution of 1-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1- yl)-5-nitrophenyl)guanidine (Intermediate 28, 1.8 g, 4.6 mmol, 1.0 eq) in n-butanol (40 ml) was added (E)-3-(dimethylamino)-1-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)prop-2- en-1-one (Intermediate 12, 0.68 g, 2.7 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 26 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2-4% methanol in dichloromethane gradient to obtain the title compound (1.5 g, yield: 63.29%) as an off-white solid. Mass m / z: 576.10 (M+H)+. Step 2: Synthesis of N1-(4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-6- To a stirred solution of 4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-N-(2- methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)-5-nitrophenyl)pyrimidin-2-amine (Step 1, 1.5 g, 2.6 mmol, 1.0 eq) in methanol (15 ml) and ethyl acetate (15 ml) was added 10% Pd / C (0.13 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (40 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (1.2 g) was used as such for next step without further purification. Mass m / z: 546.15 (M+H)+. Step 3: Synthesis of N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N1-(4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-6-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)benzene-1,3- diamine (Step 2, 1.4 g, 2.5 mmol, 1.0 eq) in DCM (15 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.95 ml, 0.5 mmol, 2.0 eq) and acryloyl chloride (0.22 ml, 2.5 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (40 ml) and washed with water (20 ml) and brine solution (20 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 (0.36 g, yield: 23.52%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 8.98 (s, 1H), 8.66 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.25 (s, 1H), 7.66 (m, 1H), 7.55 (m, 2H), 7.25 (m, 1H), 6.84 (s, 1H), 6.65 (m, 1H), 6.18 (m, 1H), 5.73 (m, 1H), 4.09 (s, 3H), 3.80 (s, 3H), 3.08 (m, 2H), 2.72 (m, 2H), 2.52 (m, 12H), 1.87 (m, 4H); Mass m / z: 600.16 (M+H)+. Example 13: Preparation of N-(4-methoxy-2-(methyl(2-morpholinoethyl)amino)-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of 1-(2-methoxy-4-(methyl(2-morpholinoethyl)amino)-5- nitrophenyl)guanidine (Intermediate 21, 1.2 g, 3.4 mmol, 1.0 eq) in n-butanol (25 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.468 g, 2.0 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.12 g, yield: 63.63% (for two steps)) as an off-white solid. Mass m / z: 519.15 (M+H)+. Step 2: Synthesis of 5-methoxy-N1-methyl-N4-(4-(1-methyl-1H-benzo[d]imidazol-2- To a stirred solution of 2-methoxy-N4-methyl-N1-(4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N4-(2-morpholinoethyl)-5-nitrobenzene-1,4-diamine (Step 1, 1.12 g, 2.1 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.9 g) was used as such for next step without further purification. Mass m / z: 489.21 (M+H)+. Step 3: Synthesis of N-(4-methoxy-2-(methyl(2-morpholinoethyl)amino)-5-((4-(1-methyl-1H- To a stirred solution of 5-methoxy-N1-methyl-N4-(4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N1-(2-morpholinoethyl)benzene-1,2,4-triamine (Step 2, 0.9 g, 1.8 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.68 ml, 3.6 mmol, 2.0 eq) and acryloyl chloride (0.15 ml, 1.8 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (40 ml) and washed with water (20 ml) and brine solution (20 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 (0.36 g, yield: 36.36%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.30 (s, 1H), 8.63 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.37 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.59 (m, 2H), 7.35 (m, 1H), 7.29 (m, 1H), 6.96 (s, 1H), 6.60 (m, 1H), 6.19 (m, 1H), 5.73 (m, 1H), 4.09 (s, 3H), 3.80 (s, 3H), 3.55 (m, 4H), 3.00 (m, 2H), 2.71 (s, 3H), 2.36 (m, 6H); Mass m / z: 543.21 (M+H)+. Example 14: Preparation of N-(5-((4-(1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 0.6 g, 1.9 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one (Intermediate 2, 0.208 g, 0.9 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.7 g, yield: 78.2%) as an off-white solid. Mass m / z: 463.17 (M+H)+. Step 2: Synthesis of N4-(4-(1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N1-(2- To a stirred solution of N1-(4-(1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N4-(2- (dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine (Step 1, 0.6 g) in methanol (5 ml) and ethyl acetate (5 ml) was added 10% Pd / C (0.08 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (20 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.55 g) was used as such for next step without further purification. Mass m / z: 433.16 (M+H)+. Step 3: Synthesis of N-(5-((4-(1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-((2- To a stirred solution of N4-(4-(1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N1-(2- (dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (Step 2, 0.55 g, 1.2 mmol, 1.0 eq) in DCM (8 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.43 ml, 2.5 mmol, 2.0 eq) and acryloyl chloride (0.1 ml, 1.2 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 (0.21 g, yield: 34.2% (for two steps)) as a yellow solid.1H-NMR (500 MHz-DMSO-d6): 12.72 (s, 1H), 9.93 (s, 1H), 9.37 (s, 1H), 8.67 (s, 1H), 8.16 (s, 1H), 7.77 (m, 4H), 7.35 (m, 2H), 7.05 (s, 1H), 6.50 (m, 1H), 5.91 (m, 1H), 3.92 (s, 3H), 2.87 (m, 2H), 2.74 (s, 3H), 2.62 (m, 2H), 2.56 (s, 6H); Mass m / z: 487.16 (M+H)+. Example 15: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5- ((4-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide: Step 1: Synthesis of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-5- To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.35 g, 4.38 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2- yl)prop-2-en-1-one (Intermediate 3, 0.57 g, 1.9 mmol, 0.44 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.7 g, yield: 30.4% (for two steps)) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 8.30 (s, 1H), 8.64 (d, J = 5.0 Hz, 1H), 8.35 (s, 1H), 8.14 (s, 1H), 7.92 (d, J = 8.5 Hz, 1H), 7.70 (m, 1H), 7.64 (d, J = 5.0 Hz, 1H), 6.87 (s, 1H), 4.21 (s, 3H), 3.95 (s, 3H), 3.38 (m, 2H), 2.85 (s, 3H), 2.45 (m, 8H); Mass m / z: 545.17 (M+H)+. Step 2: Synthesis of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl-5- To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-2- nitrobenzene-1,4-diamine (Step 1, 0.6 g, 1.1 mmol, 1.0 eq) in methanol (6 ml) and ethyl acetate (6 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.55 g) was used as such for next step without further purification. Mass m / z: 515.33 (M+H)+. Step 3: Synthesis of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide: To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4- triamine (Step 2, 0.55 g, 1.0 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.4 ml, 2.0 mmol, 2.0 eq) and acryloyl chloride (0.08 ml, 1.0 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.23 g, yield: 38.0% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 9.76 (brs, 1H), 8.74 (s.1H), 8.59 (d, J = 5.0 Hz, 1H), 8.32 (brs, 1H), 8.13 (s, 1H), 7.87 (d, J = 8.5 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 5.0 Hz, 1H), 6.98 (s, 1H), 6.78 (m, 1H), 6.24 (d, J = 16.5 Hz, 1H), 5.74 (d, J = 11.0 Hz, 1H), 4.15 (s, 3H), 3.83 (s, 3H), 2.75 (m, 4H), 2.64 (s, 3H), 2.52 (s, 6H); Mass m / z: 569.39 (M+H)+. Example 16: Preparation of 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4- (5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxyphenyl)propanamide: To a stirred solution of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5- fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxyphenyl)acrylamide (Example 9, 0.05 g, 0.09 mmol) in 1,4-Dioxane (2 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (2.0 ml). The reaction mixture was allowed to room temperature and stirred for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (20 ml) and washed with saturated NaHCO3 solution (10 ml) and brine solution (10 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 (0.02 g, yield: 37.73%) as a pale brown solid.1H-NMR (500 MHz-DMSO-d6): 9.78 (s, 1H), 8.89 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 8.21 (s, 1H), 7.75 (m, 1H), 7.59 (m, 2H), 7.34 (m, 1H), 6.94 (s, 1H), 4.14 (s, 3H), 3.88 (t, J = 10.5 Hz, 2H), 3.83 (s, 3H), 3.34 (m, 2H), 3.27 (m, 2H), 3.10 (m, 2H), 2.75 (s, 3H), 2.73 (s, 3H), 2.63 (s, 3H); Mass m / z: 555.29 (M+H)+. Example 17: Preparation of 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)propanamide: To a stirred solution of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide (Example 15, 0.04 g, 0.071 mmol) in 1,4-Dioxane (3 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (3.0 ml). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (30 ml) and washed with saturated NaHCO3 solution (10 ml) and brine solution (20 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 (0.018 g, yield: 42.8%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.68 (brs, 1H), 8.70 (s, 1H), 8.60 (d, J = 8.0 Hz, 1H), 8.21 (s, 1H), 8.13 (d, J = 2.5 Hz, 1H), 7.86 (d, J = 14.5 Hz, 1H), 7.67 (dd, J = 2.5 Hz, 14.5 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 6.95 (s, 1H), 4.16 (s, 3H), 3.89 (t, J = 10.5 Hz, 2H), 3.83 (s, 3H), 3.01 (t, J = 10.5 Hz, 2H), 2.74 (m, 4H), 2.63 (s, 3H), 2.52 (s, 6H); Mass m / z: 605.59 (M+H)+. Example 18: Preparation of N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- Step 1: Synthesis of N1-(4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.36 g, 4.3 mmol, 1.0 eq) in n-butanol (30 ml) was added (E)-1-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2- en-1-one (Intermediate 13, 0.69 g, 2.6 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 1-2% methanol in dichloromethane gradient to obtain the title compound (1.8 g, yield: 80.35%) as an off-white solid. Mass m / z: 513.28 (M+H)+. Step 2: Synthesis of N4-(4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine (Step 1, 1.8 g, 3.5 mmol, 1.0 eq) in methanol (18 ml) and ethyl acetate (18 ml) was added 10% Pd / C (0.2 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (200 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (1.29 g) was used as such for next step without further purification. Mass m / z: 483.38 (M+H)+. Step 3: Synthesis of N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 1.29 g, 2.6 mmol, 1.0 eq) in DCM (15 ml) at 0 ºC, were added N,N- Diisopropylethylamine (1.0 ml, 5.2 mmol, 2.0 eq) and acryloyl chloride (0.22 ml, 2.6 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (30 ml) and brine solution (30 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 (0.35 g, yield: 24.43%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 9.79 (brs, 1H), 8.69 (s, 1H), 8.56 (d, J = 5.0 Hz, 1H), 8.37 (s, 1H), 7.84 (m, 2H), 7.53 (d, J = 5.0 Hz, 1H), 6.97 (s, 1H), 6.91 (m, 1H), 6.24 (m, 1H), 5.73 (m, 1H), 4.07 (s, 3H), 3.82 (s, 3H), 3.34 (m, 2H), 3.21 (s, 3H), 2.66 (m, 2H), 2.64 (s, 6H); Mass m / z: 537.44 (M+H)+. Example 19: Preparation of N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 5.0 g, 16.1 mmol, 1.0 eq) in n-butanol (75 ml) was added (E)-1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1- one (Intermediate 15, 2.12 g, 8.05 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (3.4 g, yield: 41.46%) as an off-white solid. Mass m / z: 511.43 (M+H)+. Step 2: Synthesis of N4-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine (Step 1, 1.2 g, 2.3 mmol, 1.0 eq) in methanol (6 ml) at 0 ºC, were added Iron (0.656 g, 11.7 mmol, 5.0 eq), AcOH (2.4 ml) and water (1.2 ml). The reaction mixture was heated to 65 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with methanol. The filtrate was evaporated under reduced pressure and the obtained residue was basified with saturated NaHCO3 solution and extracted with DCM. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (1.0 g), which was used as such for next step without further purification. Mass m / z: 481.40 (M+H)+. Step 3: Synthesis of N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide: To a stirred solution of N4-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 1.0 g, 2.0 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.76 ml, 4.0 mmol, 2.0 eq) and acryloyl chloride (0.16 ml, 2.0 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 2-3% methanol in dichloromethane gradient to obtain the title compound (0.35 g, yield: 31.53% (for two steps)) as a pale green solid.1H-NMR (500 MHz- DMSO-d6): 10.11 (s, 1H), 8.70 (s, 1H), 8.56 (m, 2H), 7.81 (m, 1H), 7.68 (m, 1H), 7.55 (d, J = 5.0Hz, 1H), 7.38 (m, 1H), 7.01 (s, 1H), 6.38 (m, 1H), 6.18 (m, 1H), 5.74 (m, 1H), 4.07 (s, 3H), 3.79 (s, 3H), 2.88 (m, 2H), 2.72 (s, 3H), 2.31 (m, 2H), 2.20 (s, 6H); Mass m / z: 535.52 (M+H)+. Example 20: Preparation of 3-chloro-N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol- 2-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)propanamide: To a stirred solution of N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide (Example 18, 0.06 g, 0.11 mmol) in 1,4-Dioxane (2.0 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (2.0 ml). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (30 ml) and washed with saturated NaHCO3 solution (10 ml) and brine solution (20 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 (0.017 g, yield: 26.56%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 9.76 (brs, 1H), 8.66 (s, 1H), 8.57 (d, J = 8.0 Hz, 1H), 8.21 (s, 1H), 7.83 (m, 2H), 7.54 (d, J = 5.0 Hz, 1H), 6.95 (s, 1H), 4.08 (s, 3H), 3.89 (t, J = 6.0 Hz, 2H), 3.82 (s, 3H), 3.32 (m, 2H), 2.98 (s, 3H), 2.75 (m, 4H), 2.64 (s, 6H); Mass m / z: 571.30 (M-H)-. Example 21: Preparation of 3-chloro-N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)propanamide: To a stirred solution of N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide (Example 19, 0.1 g, 0.18 mmol) in 1,4-Dioxane (3 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (3.0 ml). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (20 ml) and washed with saturated NaHCO3 solution (10 ml) and brine solution (10 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 1-2% methanol in dichloromethane gradient to obtain the title compound (0.044 g, yield: 41.51%) as a brown solid.1H-NMR (500 MHz-DMSO-d6): 9.78 (s, 1H), 8.85 (s, 1H), 8.59 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 7.84 (d, J = 1.5 Hz, 1H), 7.73 (d, J = 9.0 Hz, 1H), 7.59 (d, J = 5.0 Hz, 1H), 7.41 (m, 1H), 6.93 (s, 1H), 4.12 (s, 3H), 3.88 (t, J = 6.5 Hz, 2H), 3.83 (s, 3H), 3.33 (m, 2H), 3.27 (m, 2H), 3.10 (t, J = 6.5 Hz, 2H), 2.75 (s, 3H), 2.74 (s, 3H), 2.63 (s, 3H); Mass m / z: 571.60 (M+H)+. Example 22: Preparation of 2-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acetamide: To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4-triamine (Example 1- step 2, 0.2 g, 0.4 mmol, 1.0 eq) in DCM (5 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.16 ml, 0.8 mmol, 2.0 eq) and 2-chloroacetyl chloride (0.04 ml, 0.4 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 4 hours. 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 (20 ml) and brine solution (20 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 (0.086 g, yield: 38.0%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.9 (brs, 1H), 9.03 (s, 1H), 8.84 (brs, 1H), 8.71 (d, J = 5.0 Hz, 1H), 7.74 (m, 1H), 7.65 (m, 1H), 7.47 (m, 1H), 7.40 (m, 1H), 7.37 (m, 1H), 6.96 (s, 1H), 4.75 (s, 2H), 4.23 (s, 3H), 3.75 (s, 3H), 2.75 (m, 2H), 2.58 (s, 3H), 2.51 (m, 2H), 2.38 (s, 6H); Mass m / z: 523.28 (M+H)+. Example 23: Preparation of N-(2-((2-(1,1-dioxidothiomorpholino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide: Step 1: Synthesis of 4-(2-((5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-nitrophenyl)(methyl)amino)ethyl)thiomorpholine 1,1-dioxide: To a stirred solution of 1-(4-((2-(1,1-dioxidothiomorpholino)ethyl)(methyl)amino)- 2-methoxy-5-nitrophenyl)guanidine (Intermediate 22, 0.83 g, 2.0 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2- en-1-one (Intermediate 1, 0.284 g, 1.2 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 1-2% methanol in dichloromethane gradient to obtain the title compound (0.8 g, yield: 68.37% (for two steps)) as an off-white solid. Mass m / z: 567.20 (M+H)+. Step 2: Synthesis of 4-(2-((2-amino-5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- To a stirred solution of 4-(2-((5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-nitrophenyl)(methyl)amino)ethyl)thiomorpholine 1,1-dioxide (Step 1, 0.8 g, 1.4 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.5 g) was used as such for next step without further purification. Mass m / z: 537.37 (M+H)+. Step 3: Synthesis of N-(2-((2-(1,1-dioxidothiomorpholino)ethyl)(methyl)amino)-4-methoxy-5- ((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of 4-(2-((2-amino-5-methoxy-4-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)thiomorpholine 1,1-dioxide (Step 2, 0.5 g, 0.9 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.35 ml, 1.8 mmol, 2.0 eq) and acryloyl chloride (0.08 ml, 0.9 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 1-2% methanol in dichloromethane gradient to obtain the title compound (0.14 g, yield: 25.34% (for two steps)) as a pale brown solid.1H-NMR (500 MHz- DMSO-d6): 9.28 (s, 1H), 8.62 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.36 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.36 (m, 1H), 7.29 (m, 1H), 6.95 (s, 1H), 6.58 (m, 1H), 6.19 (m, 1H), 5.73 (m, 1H), 4.10 (s, 3H), 3.81 (s, 3H), 3.02 (m, 4H), 2.99 (m, 2H), 2.91 (m, 4H), 2.71 (s, 3H), 2.62 (m, 2H); Mass m / z: 591.43 (M+H)+. Example 24: Preparation of N-(2-((2-hydroxyethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of 1-(4-((2-hydroxyethyl)(methyl)amino)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 23, 1.86 g, 6.56 mmol, 1.0 eq) in n-butanol (30 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.902 g, 3.93 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 1-2% methanol in dichloromethane gradient to obtain the title compound (1.3 g, yield: 35.65% (for two steps)) as an off-white solid. Mass m / z: 450.14 (M+H)+. Step 2: Synthesis of 2-((2-amino-5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- To a stirred solution of 2-((5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-nitrophenyl)(methyl)amino)ethan-1-ol (Step 1, 0.7 g, 1.55 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.5 g) was used as such for next step without further purification. Mass m / z: 420.25 (M+H)+. Step 3: Synthesis of N-(2-((2-hydroxyethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- To a stirred solution of 2-((2-amino-5-methoxy-4-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethan-1-ol (Step 2, 0.5 g, 1.1 mmol, 1.0 eq) in DCM (8 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.44 ml, 2.2 mmol, 2.0 eq) and acryloyl chloride (0.10 ml, 1.1 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 0-1% methanol in dichloromethane gradient to obtain the title compound (0.11 g, yield: 19.5%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.61 (s, 1H), 8.65 (s, 1H), 8.62 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 5.0 Hz, 1H), 7.34 (m, 1H), 7.28 (m, 1H), 6.94 (s, 1H), 6.51 (m, 1H), 6.18 (m, 1H), 5.70 (m, 1H), 5.33 (t, J = 5.0 Hz, 1H), 4.08 (s, 3H), 3.79 (s, 3H), 3.61 (m, 2H), 2.87 (m, 2H), 2.73 (s, 3H); Mass m / z: 474.50 (M+H)+. Example 25: Preparation of N-(5-((4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.0 g, 3.2 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1- one (Intermediate 16, 0.508 g, 1.9 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.71 g, yield: 43.29%) as an off-white solid. Mass m / z: 511.31 (M+H)+. Step 2: Synthesis of N4-(4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine (Step 1, 0.7 g, 1.3 mmol, 1.0 eq) in methanol (3.5 ml) at 0 ºC, were added Iron (0.383 g, 6.8 mmol, 5.0 eq), AcOH (1.4 ml) and water (0.7 ml). The reaction mixture was heated to 65 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with methanol. The filtrate was evaporated under reduced pressure and the obtained residue was basified with saturated NaHCO3 solution and extracted with DCM. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (0.6 g), which was used as such for next step without further purification. Mass m / z: 481.34 (M+H)+. Step 3: Synthesis of N-(5-((4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.6 g, 1.25 mmol, 1.0 eq) in DCM (8 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.48 ml, 3.75 mmol, 3.0 eq) and acryloyl chloride (0.1 ml, 1.25 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.178 g, yield: 26.70% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.04 (s, 1H), 8.70 (s, 1H), 8.57 (d, J = 8.5 Hz, 1H), 8.51 (s, 1H), 7.76 (m, 2H), 7.56 (d, J = 8.5 Hz, 1H), 7.31 (m, 1H), 7.01 (s, 1H), 6.42 (m, 1H), 6.18 (m, 1H), 5.73 (m, 1H), 4.07 (s, 3H), 3.80 (s, 3H), 2.94 (m, 2H), 2.71 (s, 3H), 2.42 (m, 2H), 2.29 (s, 6H); Mass m / z: 535.25 (M+H)+. Example 26: Preparation of N-(5-((4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.35 g, 4.38 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 4, 0.905 g, 3.2 mmol, 0.73 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.6 g, yield: 35.29% (for two steps)) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 8.81 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.21 (s, 1H), 7.70 (d, J = 2.0 Hz, 1H), 7.56 (d, J = 5.0 Hz, 1H), 7.36 (dd, J = 2.0 Hz, 11.5 Hz, 1H), 6.80 (s, 1H), 4.27 (s, 3H), 3.91 (s, 3H), 2.85 (3H), 2.64 (m, 4H), 2.15 (s, 6H); Mass m / z: 529.10 (M+H)+. Step 2: Synthesis of N4-(4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- To a stirred solution of N1-(4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol- 2-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene- 1,4-diamine (Step 1, 0.9 g, 1.7 mmol, 1.0 eq) in methanol (5 ml) at 0 ºC, were added Iron (0.48 g, 8.5 mmol, 5.0 eq), AcOH (1.8 ml) and water (1 ml). The reaction mixture was heated to 65 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with methanol. The filtrate was evaporated under reduced pressure and the obtained residue was basified with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (0.82 g, yield: 96.6%), which was used as such for next step without further purification. Mass m / z: 499.20 (M+H)+. Step 3: Synthesis of N-(5-((4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of N4-(4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol- 2-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.8 g, 1.6 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.6 ml, 3.2 mmol, 2.0 eq) and acryloyl chloride (0.13 ml, 1.6 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 (0.32 g, yield: 36.0% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 10.07 (brs, 1H), 8.73 (s, 1H), 8.60 (d, J = 8.5 Hz, 1H), 8.50 (brs, 1H), 7.69 (d, J = 2.5 Hz, 1H), 7.52 (d, J = 8.5 Hz, 1H), 7.35 (dd, J = 2.5 Hz, 19.0 Hz, 1H), 7.01 (s, 1H), 6.41 (m, 1H), 6.21 (m, 1H), 5.72 (m, 1H), 4.21 (s, 3H), 3.80 (s, 3H), 2.93 (m, 2H), 2.70 (s, 3H), 2.52 (m, 2H), 2.27 (s, 6H); Mass m / z: 553.32 (M+H)+. Example 27: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-ethyl-5- fluoro-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.35 g, 4.38 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-ethyl-5-fluoro-1H-benzo[d]imidazol-2-yl)prop-2-en- 1-one (Intermediate 6, 0.68 g, 2.6 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.4 g, yield: 63.3% (for two steps)) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 8.78 (s, 1H), 8.58 (d, J = 5.0 Hz, 1H), 8.04 (s, 1H), 7.70 (dd, J = 5.0 Hz, 9.0 Hz, 1H), 7.58 (d, J = 5.0 Hz, 1H), 7.54 (dd, J = 2.5 Hz, 9.5 Hz, 1H), 7.22 (m, 1H), 6.81 (s, 1H), 4.66 (m, 2H), 3.88 (s, 3H), 3.29 (m, 2H), 2.86 (s, 3H), 2.52 (m, 2H), 2.17 (s, 6H), 1.06 (t, J = 6.5 Hz, 3H); Mass m / z: 509.25 (M+H)+. Step 2: Synthesis of N1-(2-(dimethylamino)ethyl)-N4-(4-(1-ethyl-5-fluoro-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methylbenzene-1,2,4-triamine: To a stirred solution of N1-(2-(dimethylamino)ethyl)-N4-(4-(1-ethyl-5-fluoro-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4-diamine (Step 1, 1.4 g, 2.7 mmol, 1.0 eq) in methanol (15 ml) and ethyl acetate (15 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (1.0 g) was used as such for next step without further purification. Mass m / z: 479.42 (M+H)+. Step 3: Synthesis of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-ethyl-5-fluoro- To a stirred solution of N1-(2-(dimethylamino)ethyl)-N4-(4-(1-ethyl-5-fluoro-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (Step 2, 0.7 g, 1.4 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.8 ml, 4.3 mmol, 3.0 eq) and acryloyl chloride (0.11 ml, 1.4 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.32 g, yield: 41.0%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.11 (brs, 1H), 8.76 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.38 (s, 1H), 7.66 (m, 1H), 7.54 (m, 2H), 7.21 (m, 1H), 7.02 (s, 1H), 6.38 (m, 1H), 6.19 (d, J = 17.0 Hz, 1H), 5.73 (d, J = 10.0 Hz, 1H), 4.61 (q, J = 7.0 Hz, 2H), 3.76 (s, 3H), 2.90 (m, 2H), 2.72 (s, 3H), 2.36 (m, 2H), 2.23 (s, 6H), 1.01 (t, J = 7.0 Hz, 3H); Mass m / z: 533.47 (M+H)+. Example 28: Preparation of N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5- ((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of 1-(4-((3-(dimethylamino)propyl)(methyl)amino)-2- methoxy-5-nitrophenyl)guanidine (Intermediate 24, 1.36 g, 4.3 mmol, 1.0 eq) in n-butanol (25 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2- en-1-one (Intermediate 1, 0.602 g, 2.6 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.0 g, yield: 46.7%) as an off-white solid. Mass m / z: 491.26 (M+H)+. Step 2: Synthesis of N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methyl-N4-(4-(1-methyl- To a stirred solution of N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-2-nitrobenzene-1,4-diamine (Step 1, 1.0 g, 2.0 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.13 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.6 g) was used as such for next step without further purification. Mass m / z: 461.29 (M+H)+. Step 3: Synthesis of N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5-((4-(1- To a stirred solution of N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methyl-N4- (4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4-triamine (Step 2, 0.6 g, 1.3 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.73 ml, 3.9 mmol, 3.0 eq) and acryloyl chloride (0.11 ml, 1.3 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.2 g, yield: 29.8%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.11 (s, 1H), 8.64 (s, 1H), 8.54 (d, J = 5.0 Hz, 1H), 8.31 (s, 1H), 7.76 (m, 1H), 7.58 (m, 2H), 7.35 (m, 1H), 7.29 (m, 1H), 6.90 (s, 1H), 6.63 (m, 1H), 6.17 (m, 1H), 5.71 (m, 1H), 4.08 (s, 3H), 3.80 (s, 3H), 2.85 (m, 2H), 2.66 (s, 3H), 2.27 (m, 2H), 2.13 (s, 6H), 1.61 (m, 2H); Mass m / z: 515.48 (M+H)+. Example 29: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1- isopropyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(2-(dimethylamino)ethyl)-N4-(4-(1-isopropyl-1H-benzo[d]imidazol- 2-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4-diamine: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.35 g, 4.38 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-isopropyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1- one (Intermediate 7, 0.675 g, 2.6 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.0 g, yield: 45.5% (for two steps)) as an off-white solid. Mass m / z: 505.35 (M+H)+. Step 2: Synthesis of N1-(2-(dimethylamino)ethyl)-N4-(4-(1-isopropyl-1H-benzo[d]imidazol- To a stirred solution of N1-(2-(dimethylamino)ethyl)-N4-(4-(1-isopropyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methyl-2-nitrobenzene-1,4-diamine (Step 1, 1.0 g, 1.9 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.9 g) was used as such for next step without further purification. Mass m / z: 475.32 (M+H)+. Step 3: Synthesis of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-isopropyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide: To a stirred solution of N1-(2-(dimethylamino)ethyl)-N4-(4-(1-isopropyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-methoxy-N1-methylbenzene-1,2,4-triamine (Step 2, 0.9 g, 1.8 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (1.1 ml, 5.6 mmol, 3.0 eq) and acryloyl chloride (0.15 ml, 1.8 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.39 g, yield: 39.0%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.14 (brs, 1H), 8.72 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.36 (brs, 1H), 7.78 (m, 1H), 7.71 (m, 1H), 7.47 (d, J = 5.0 Hz, 1H), 7.25 (m, 2H), 7.04 (s, 1H), 6.38 (m, 1H), 6.19 (d, J = 17.0 Hz, 1H), 5.89 (m, 1H), 5.72 (m, 1H), 3.77 (s, 3H), 2.88 (m, 2H), 2.71 (s, 3H), 2.32 (m, 2H), 2.21 (s, 6H), 1.36 (d, J = 7.0 Hz, 6H); Mass m / z: 529.37 (M+H)+. Example 30: Preparation of N-(5-((4-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.35 g, 4.38 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 5, 0.905 g, 3.2 mmol, 0.73 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.64 g, yield: 37.6% (for two steps)) as an off-white solid.1H-NMR (500 MHz-DMSO-d6): 8.79 (s, 1H), 8.62 (d, J = 5.0 Hz, 1Hz), 8.26 (s, 1H), 7.77 (d, J = 1.5 Hz, 1H), 7.61 (d, J = 5.0 Hz, 1H), 7.32 (dd, J = 1.5 Hz, 10.5 Hz, 1H), 6.82 (s, 1H), 4.15 (s, 3H), 3.92 (s, 3H), 3.27 (m, 2H), 2.85 (s, 3H), 2.52 (m, 2H), 2.18 (s, 6H); Mass m / z: 529.37 (M+H)+. Step 2: Synthesis of N4-(4-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- To a stirred solution of N1-(4-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol- 2-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene- 1,4-diamine (Step 1, 0.9 g, 1.7 mmol, 1.0 eq) in methanol (5 ml) at 0 ºC, were added Iron (0.48 g, 8.5 mmol, 5.0 eq), AcOH (1.8 ml) and water (1 ml). The reaction mixture was heated to 65 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with methanol. The filtrate was evaporated under reduced pressure and the obtained residue was basified with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (0.81 g, yield: 96.4%), which was used as such for next step without further purification. Mass m / z: 499.26 (M+H)+. Step 3: Synthesis of N-(5-((4-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of N4-(4-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol- 2-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.8 g, 1.6 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.6 ml, 3.2 mmol, 2.0 eq) and acryloyl chloride (0.13 ml, 1.6 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 (0.36 g, yield: 40.0% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 10.08 (brs, 1H), 8.75 (s, 1H), 8.58 (d, J = 5.0 Hz, 1H), 8.52 (brs, 1H), 7.71 (d, J = 1.5 Hz, 1H), 7.56 (d, J = 5.0 Hz, 1H), 7.29 (dd, J = 1.5 Hz, 10.5 Hz, 1H), 7.01 (s, 1H), 6.39 (m, 1H), 6.21 (m, 1H), 5.73 (m, 1H), 4.07 (s, 3H), 3.79 (s, 3H), 2.91 (m, 2H), 2.71 (s, 3H), 2.52 (m, 2H), 2.24 (s, 6H); Mass m / z: 553.38 (M+H)+. Example 31: Preparation of N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((3-(dimethylamino)propyl)(methyl)amino)-4- methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of 1-(4-((3-(dimethylamino)propyl)(methyl)amino)-2- methoxy-5-nitrophenyl)guanidine (Intermediate 24, 1.0 g, 3.0 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 15, 0.487 g, 1.8 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.51 g, yield: 31.6%) as an off-white solid. Mass m / z: 525.33 (M+H)+. Step 2: Synthesis of N4-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(3-(dimethylamino)propyl)-2-methoxy-N4-methyl-5-nitrobenzene- 1,4-diamine (Step 1, 0.5 g, 0.9 mmol, 1.0 eq) in methanol (2.5 ml) at 0 ºC, were added Iron (0.266 g, 4.7 mmol, 5.0 eq), AcOH (1.0 ml) and water (0.5 ml). The reaction mixture was heated to 65 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with methanol. The filtrate was evaporated under reduced pressure and the obtained residue was basified with saturated NaHCO3 solution and extracted with DCM. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (0.4 g), which was used as such for next step without further purification. Mass m / z: 495.30 (M+H)+. Step 3: Synthesis of N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.4 g, 0.8 mmol, 1.0 eq) in DCM (5 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.31 ml, 2.4 mmol, 3.0 eq) and acryloyl chloride (0.06 ml, 0.8 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (10 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 (0.15 g, yield: 28.7% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 9.15 (s, 1H), 8.68 (s, 1H), 8.57 (m, 1H), 8.26 (s, 1H), 7.81 (s, 1H), 7.68 (m, 1H), 7.55 (m, 1H), 7.39 (m, 1H), 6.92 (s, 1H),6.69 (m, 1H), 6.19 (m, 1H), 5.73 (m, 1H), 4.10 (s, 3H), 3.82 (s, 3H), 3.06 (m, 2H), 2.91 (s, 3H), 2.62 (m, 2H), 2.66 (s, 6H), 1.81 (m, 2H); Mass m / z: 549.28 (M+H)+. Example 32: Preparation of N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(diethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of 1-(4-((2-(diethylamino)ethyl)(methyl)amino)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 25, 1.18 g, 3.48 mmol, 1.0 eq) in n-butanol (15 ml) was added (E)-1-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1- one (Intermediate 15, 0738 g, 2.10 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.52 g, yield: 27.65% (for two steps)) as an off-white solid. Mass m / z: 539.29 (M+H)+. Step 2: Synthesis of N4-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(diethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine (Step 1, 0.5 g, 0.94 mmol, 1.0 eq) in methanol (2.5 ml) at 0 ºC, were added Iron (0.264 g, 4.75 mmol, 5.0 eq), AcOH (1.0 ml) and water (0.5 ml). The reaction mixture was heated to 65 ºC for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with methanol. The filtrate was evaporated under reduced pressure and the obtained residue was basified with saturated NaHCO3solution and extracted with DCM. The organic layer was separated, dried over sodium sulphate, filtered and concentrated under reduced pressure to obtain the title compound (0.45 g), which was used as such for next step without further purification. Mass m / z: 509.32 (M+H)+. Step 3: Synthesis of N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(diethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.45 g, 0.83 mmol, 1.0 eq) in DCM (5 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.48 ml, 2.60 mmol, 3.0 eq) and acryloyl chloride (0.075 ml, 0.83 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (10 ml) and brine solution (10 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 (0.16 g, yield: 30.76% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 9.72 (s, 1H), 8.69 (s, 1H), 8.56 (d, J = 5.0 Hz, 1H), 8.49 (s, 1H), 7.81 (d, J = 2.0 Hz, 1H), 7.66 (d, J = 9.0 Hz, 1H), 7.55 (d, J = 5.0 Hz, 1H), 7.38 (m, 1H), 6.96 (s, 1H), 6.44 (m, 1H), 6.18 (m, 1H), 5.71 (m, 1H), 4.07 (s, 3H), 3.79 (s, 3H), 2.86 (m, 2H), 2.71 (s, 3H), 2.52 (m, 6H), 0.95 (t, J = 7.0 Hz, 6H); Mass m / z: 563.44 (M+H)+. Example 33: Preparation of N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 0.952 g, 3.0 mmol) in n-butanol (20 ml) was added (E)-1-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1- one (Intermediate 10, 0.406 g, 1.5 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.9 g, yield: 57.3%) as an off-white solid. Mass m / z: 513.36 (M+H)+. Step 2: Synthesis of N4-(4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4-triamine: To a stirred solution of N1-(4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine (Step 1, 0.9 g) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.76 g) was used for next step without further purification. Mass m / z: 483.32 (M+H)+. Step 3: Synthesis of N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.87 g, 1.8 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (1.0 ml, 5.4 mmol, 3.0 eq) and acryloyl chloride (0.145 ml, 1.8 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 (0.26 g, yield: 26.8%) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.05 (brs, 1H), 8.72 (s, 1H), 8.60 (d, J = 5.0 Hz, 1H), 8.52 (brs, 1H), 7.53 (d, J = 5.0 Hz, 1H), 7.45 (m, 1H), 7.27 (m, 1H), 7.01 (s, 1H), 6.42 (m, 1H), 6.22 (m, 1H), 5.73 (m, 1H), 4.22 (s, 3H), 3.80 (s, 3H), 2.91 (m, 2H), 2.70 (s, 3H), 2.42 (m, 2H), 2.22 (s, 6H); Mass m / z: 537.31 (M+H)+. Example 34: Preparation of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5- ((4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.1 g, 3.5 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)prop-2- en-1-one (Intermediate 17, 0.625 g, 2.10 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.6 g, yield: 31.5%) as an off-white solid. Mass m / z: 545.31 (M+H)+. Step 2: Synthesis of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4-(4-(1-(2,2,2- To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-2- nitro-N4-(4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,4- diamine (Step 1, 0.6 g, 1.10 mmol, 1.0 eq) in methanol (5 ml) and ethyl acetate (5 ml) was added 10% Pd / C (0.1 g, 50% wet). The reaction mixture was stirred at room temperature under hydrogen atmosphere 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 methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.55 g) was used as such for next step without further purification. Mass m / z: 515.21 (M+H)+. Step 3: Synthesis of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- To a stirred solution of N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methyl-N4- (4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4- triamine (Step 2, 0.55 g, 1.07 mmol, 1.0 eq) in DCM (8 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.59 ml, 3.21 mmol, 3.0 eq) and acryloyl chloride (0.09 ml, 1.07 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (10 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 (0.162 g, yield: 26.94% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.75 (brs, 1H), 8.93 (s, 1H), 8.58 (d, J = 5.0 Hz, 1H), 8.32 (m, 1H), 7.79 (m, 2H), 7.60 (d, J = 5.0 Hz, 1H), 7.42 (m, 1H), 7.35 (m, 1H), 7.00 (s, 1H), 6.96 (m, 1H), 6.24 (m, 1H), 5.95 (m, 2H), 5.73 (m, 1H), 3.80 (s, 3H), 2.67 (m, 2H), 2.63 (s, 3H), 2.54 (m, 2H), 2.48 (s, 6H); Mass m / z: 569.33 (M+H)+. Example 35: Preparation of N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5- ((4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- Step 1: Synthesis of N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methyl-2-nitro-N4-(4-(1- To a stirred solution of 1-(4-((3-(dimethylamino)propyl)(methyl)amino)-2- methoxy-5-nitrophenyl)guanidine (Intermediate 24, 1.13 g, 3.5 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol- 2-yl)prop-2-en-1-one (Intermediate 17, 0.625 g, 2.10 mmol, 0.6 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.65 g, yield: 33.3%) as an off-white solid. Mass m / z: 559.27 (M+H)+. Step 2: Synthesis of N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methyl-N4-(4-(1-(2,2,2- To a stirred solution of N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methyl-2- nitro-N4-(4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,4- diamine (Step 1, 0.65 g, 1.16 mmol, 1.0 eq) in methanol (6 ml) and ethyl acetate (6 ml) was added 10% Pd / C (0.08 g, 50% wet). The reaction mixture was stirred at room temperature under hydrogen atmosphere 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 methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.6 g) was used as such for next step without further purification. Mass m / z: 529.30 (M+H)+. Step 3: Synthesis of N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5-((4-(1- To a stirred solution of N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methyl-N4- (4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4- triamine (Step 2, 0.6 g, 1.13 mmol, 1.0 eq) in DCM (8 ml) at 0 ºC, were added N,N- Diisopropylethylamine (0.62 ml, 3.40 mmol, 3.0 eq) and acryloyl chloride (0.1 ml, 1.13 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (40 ml) and washed with water (20 ml) and brine solution (20 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 (0.24 g, yield: 36.0% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 9.11 (s, 1H), 8.91 (s, 1H), 8.57 (d, J = 5.0 Hz, 1H), 8.19 (s, 1H), 7.79 (m, 2H), 7.59 (d, J = 5.0 Hz, 1H), 7.41 (m, 1H), 7.37 (m, 1H), 6.92 (s, 1H), 6.67 (m, 1H), 6.18 (m, 1H), 5.97 (m, 2H), 5.70 (m, 1H), 3.79 (s, 3H), 2.89 (m, 2H), 2.66 (s, 3H), 2.54 (m, 2H), 2.47 (s, 6H), 1.75 (m, 2H); Mass m / z: 583.28 (M+H)+. Example 36: Preparation of N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((3-(dimethylamino)propyl)(methyl)amino)-4- methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- N4-(3-(dimethylamino)propyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4-diamine: To a stirred solution of 1-(4-((3-(dimethylamino)propyl)(methyl)amino)-2- methoxy-5-nitrophenyl)guanidine (Intermediate 24, 0.816 g, 2.5 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 10, 0.338 g, 1.2 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 26 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.85 g, yield: 64.3% (for two steps)) as an off-white solid. Mass m / z: 527.25 (M+H)+. Step 2: Synthesis of N4-(4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(3-(dimethylamino)propyl)-2-methoxy-N4-methyl-5-nitrobenzene- 1,4-diamine (Step 1, 0.85 g) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.12 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.79 g) was used for next step without further purification. Mass m / z: 497.35 (M+H)+. Step 3: Synthesis of N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.79 g, 1.59 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (2.35 ml, 12.74 mmol, 8.0 eq) and acryloyl chloride (0.128 ml, 1.59 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (40 ml) and washed with water (20 ml) and brine solution (20 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 (0.284 g, yield: 32.4% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 9.15 (s, 1H), 8.69 (s, 1H), 8.59 (d, J = 5.0 Hz, 1H), 8.27 (s, 1H), 7.52 (d, J = 5.0 Hz, 1H), 7.44 (m, 1H), 7.25 (m, 1H), 6.91 (s, 1H), 6.08 (m, 1H), 5.87 (m, 1H), 5.71 (m, 1H), 4.23 (s, 3H), 3.82 (s, 3H), 2.89 (m, 2H), 2.65 (s, 3H), 2.54 (m, 2H), 2.48 (s, 6H), 1.75 (m, 2H); Mass m / z: 551.40 (M+H)+. Example 37: Preparation of N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 0.952 g, 3.0 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3-(dimethylamino)prop- 2-en-1-one (Intermediate 11, 0.406 g, 1.5 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.8 g, yield: 50.95%) as an off-white solid. Mass m / z: 513.36 (M+H)+. Step 2: Synthesis of N4-(4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine (Step 1, 0.8 g, 1.5 mmol, 1.0 eq) in methanol (8 ml) and ethyl acetate (8 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.73 g) was used for next step without further purification. Mass m / z: 483.32 (M+H)+. Step 3: Synthesis of N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.73 g, 1.5 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N- Diisopropylethylamine (2.23 ml, 12.1 mmol, 8.0 eq) and acryloyl chloride (0.122 ml, 1.5 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.24 g, yield: 29.76% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 10.10 (brs, 1H), 8.72 (s, 1H), 8.57 (d, J = 5.0 Hz, 1H), 8.52 (brs, 1H), 7.55 (d, J = 5.0 Hz, 1H), 7.47 (m, 1H), 7.18 (m, 1H), 7.01 (s, 1H), 6.38 (m, 1H), 6.19 (m, 1H), 5.73 (m, 1H), 4.05 (s, 3H), 3.79 (s, 3H), 2.89 (m, 2H), 2.72 (s, 3H), 2.46 (m, 2H), 2.22 (s, 6H); Mass m / z: 537.31 (M+H)+. Example 38: Preparation of N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((3-(dimethylamino)propyl)(methyl)amino)-4- methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of 1-(4-((3-(dimethylamino)propyl)(methyl)amino)-2- methoxy-5-nitrophenyl)guanidine (Intermediate 24, 0.952 g, 3.0 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 11, 0.406 g, 1.5 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 26 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.0 g, yield: 62.11%) as an off-white solid. Mass m / z: 527.32 (M+H)+. Step 2: Synthesis of N4-(4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N1-(4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(3-(dimethylamino)propyl)-2-methoxy-N4-methyl-5-nitrobenzene- 1,4-diamine (Step 1, 1.0 g) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.12 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.9 g) was used for next step without further purification. Mass m / z: 497.46 (M+H)+. Step 3: Synthesis of N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of N4-(4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(3-(dimethylamino)propyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine (Step 2, 0.9 g, 1.8 mmol, 1.0 eq) in DCM (10 ml) at 0°C, were added N,N- Diisopropylethylamine (2.68 ml, 14.5 mmol, 8.0 eq) and acryloyl chloride (0.146 ml, 1.8 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 (0.21 g, yield: 21.06% (for two steps)) as a pale yellow solid.1H-NMR (500 MHz- DMSO-d6): 9.12 (s, 1H), 8.71 (s, 1H), 8.56 (d, J = 5.0 Hz, 1H), 8.27 (s, 1H), 7.54 (d, J = 5.0 Hz, 1H), 7.46 (m, 1H), 7.18 (m, 1H), 6.90 (s, 1H), 6.65 (m, 1H), 6.19 (m, 1H), 5.72 (m, 1H), 4.06 (s, 3H), 3.80 (s, 3H), 2.87 (m, 2H), 2.66 (s, 3H), 2.52 (m, 2H), 2.34 (s, 6H), 1.68 (m, 2H); Mass m / z: 551.33 (M+H)+. Example 39: Preparation of N-(5-((4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)- 4-methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 0.952 g, 3.0 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 8, 0.510 g, 1.5 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatograph by using 2% methanol in dichloromethane gradient to obtain the title compound (0.5 g, yield: 28.24%) as an off-white solid. Mass m / z: 581.30 (M+H)+. Step 2: Synthesis of N4-(4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine: To a stirred solution of N1-(4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4- methyl-5-nitrobenzene-1,4-diamine (Step 1, 0.51 g) in methanol (5 ml) and ethyl acetate (5 ml) was added 10% Pd / C (0.05 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.48 g) was used for next step without further purification. Mass m / z: 551.33 (M+H)+. Step 3: Synthesis of N-(5-((4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of N4-(4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1- methylbenzene-1,2,4-triamine (Step 2, 0.48 g, 0.8 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (0.96 ml, 6.2 mmol, 6.0 eq) and acryloyl chloride (0.0789 ml, 0.8 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 (0.170 g, yield: 32.24% (for two steps)) as a pale yellow solid.1H- NMR (500 MHz-DMSO-d6): 10.08 (brs, 1H), 8.98 (s, 1H), 8.62 (d, J = 5.0 Hz, 1H), 8.42 (brs, 1H), 7.56 (m, 2H), 7.39 (m, 1H), 7.02 (s, 1H), 6.39 (m, 1H), 6.18 (m, 1H), 5.9 (m, 2H), 5.72 (m, 1H), 3.78 (s, 3H), 2.89 (m, 2H), 2.72 (s, 3H), 2.33 (m, 2H), 2.21 (s, 6H); Mass m / z: 605.18 (M+H)+. Example 40: Preparation of N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)- 4-methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 0.952 g, 3.0 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-1-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 9, 0.51 g, 1.5 mmol, 0.5 eq). The reaction mixture was heated to 100 ºC for about 24 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (0.65 g, yield: 36.7%) as an off-white solid. Mass m / z: 581.23 (M+H)+. Step 2: Synthesis of N4-(4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine: To a stirred solution of N1-(4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4- methyl-5-nitrobenzene-1,4-diamine (Step 1, 0.65 g) in methanol (7 ml) and ethyl acetate (7 ml) was added 10% Pd / C (0.05 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.59 g) was used for next step without further purification. Mass m / z: 551.24 (M+H)+. Step 3: Synthesis of N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of N4-(4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1- methylbenzene-1,2,4-triamine (Step 2, 0.64 g, 1.1 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (1.28 ml, 6.9 mmol, 6.0 eq) and acryloyl chloride (0.094 ml, 1.1 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (20 ml) and brine solution (20 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 (0.15 g, yield: 21.3% (for two steps)) as a pale yellow solid.1H- NMR (500 MHz-DMSO-d6): 10.11 (brs, 1H), 8.98 (s, 1H), 8.59 (d, J = 5.0 Hz, 1H), 8.44 (brs, 1H), 7.70 (m, 1H), 7.58 (m, 1H), 7.30 (m, 1H), 7.02 (s, 1H), 6.39 (m, 1H), 6.21 (m, 1H), 5.92 (m, 2H), 5.74 (m, 1H), 3.78 (s, 3H), 2.91 (m, 2H), 2.71 (s, 3H), 2.33 (m, 2H), 2.23 (s, 6H); Mass m / z: 605.31 (M+H)+. Example 41: Preparation of 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)propanamide: To a stirred solution of N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxy-5-((4-(1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)acrylamide (Example 36, 0.1 g, 0.17 mmol) in 1,4-Dioxane (3 ml) at 0 ºC, was added 4N HCl in 1,4-Dioxane (3.0 ml). The reaction mixture was allowed to room temperature and stirred for about 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was concentrated under reduced pressure and the residue was diluted with DCM (30 ml) and washed with saturated NaHCO3 solution (10 ml) and brine solution (20 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 1-2% methanol in dichloromethane gradient to obtain the title compound (0.038 g, yield: 35.8%) as a pale brown solid.1H-NMR (500 MHz-DMSO-d6): 8.89 (s, 1H), 8.58 (d, J = 5.0 Hz, 1H), 8.42 (m, 1H), 7.79 (m, 3H), 7.61 (d, J = 5.0 Hz, 1H), 7.42 (m, 1H), 7.35 (m, 1H), 6.99 (s, 1H), 5.94 (m, 2H), 3.87 (m, 2H), 3.79 (s, 3H), 2.90 (m, 4H), 2.70 (s, 3H), 2.52 (m, 2H), 2.25 (s, 6H); Mass m / z: 605.57 (M+H)+. Example 42: Preparation of N-(5-((4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)- 4-methoxyphenyl)acrylamide: Step 1: Synthesis of N1-(4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4-methyl-5-nitrobenzene-1,4- diamine: To a stirred solution of 1-(4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy- 5-nitrophenyl)guanidine (Intermediate 18, 1.36 g, 4.3 mmol, 1.0 eq) in n-butanol (25 ml) was added (E)-1-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)-3- (dimethylamino)prop-2-en-1-one (Intermediate 14, 1.16 g, 3.5 mmol, 0.8 eq). The reaction mixture was heated to 100 ºC for about 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2-3% methanol in dichloromethane gradient to obtain the title compound (0.8 g, yield: 32.0%) as an off-white solid. Mass m / z: 581.32 (M+H)+. Step 2: Synthesis of N4-(4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1-methylbenzene-1,2,4- triamine: To a stirred solution of N1-(4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N4-(2-(dimethylamino)ethyl)-2-methoxy-N4- methyl-5-nitrobenzene-1,4-diamine (Step 1, 1.2 g, 2.06 mmol, 1.0 eq) in methanol (15 ml) and ethyl acetate (15 ml) was added 10% Pd / C (0.15 g, 50% wet). The reaction mixture was stirred at room temperature under hydrogen atmosphere for about 4 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was filtered through celite pad and washed with methanol and ethyl acetate (100 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.9 g) was used as such for next step without further purification. Mass m / z: 551.35 (M+H)+. Step 3: Synthesis of N-(5-((4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide: To a stirred solution of N4-(4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)-N1-(2-(dimethylamino)ethyl)-5-methoxy-N1- methylbenzene-1,2,4-triamine (Step 2, 0.9 g, 1.6 mmol, 1.0 eq) in DCM (10 ml) at 0 ºC, were added N,N-Diisopropylethylamine (1.81 ml, 9.8 mmol, 6.0 eq) and acryloyl chloride (0.13 ml, 1.6 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for about 3 hours. 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 (30 ml) and brine solution (30 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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.32 g, yield: 32.38%) as a yellow solid.1H-NMR (500 MHz-DMSO-d6): 10.11 (s, 1H), 8.94 (s, 1H), 8.58 (d, J = 5.0 Hz, 1H), 8.46 (s, 1H), 7.92 (m, 1H), 7.55 (m, 1H), 7.55 (d, J = 5.0 Hz, 1H), 7.02 (s, 1H), 6.38 (m, 1H), 6.21 (m, 1H), 5.89 (m, 2H), 5.74 (m, 1H), 3.77 (s, 3H), 2.88 (m, 2H), 2.73 (s, 3H), 2.36 (m, 2H), 2.22 (s, 6H); Mass m / z: 605.43 (M+H)+. Example 43: Preparation of (S)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: Step 1: Synthesis of (S)-1-(5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-nitrophenyl)pyrrolidin-3-ol: To a stirred solution of (S)-1-(4-(3-hydroxypyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 29, 1.0 g, 3.1 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.53 g, 1.86 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.5 g, yield: 35.7%) as an off-white solid. Mass m / z: 462.21 (M+H)+. Step 2: Synthesis of (S)-1-(2-amino-5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- To a stirred solution of (S)-1-(5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-nitrophenyl)pyrrolidin-3-ol (Step 1, 0.5 g, 1.08 mmol, 1.0 eq) in methanol (5 ml) and ethyl acetate (5 ml) was added 10% Pd / C (0.05 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.2 g, yield: 42.8%) was used as such for next step without further purification. Mass m / z: 432.13 (M+H)+. Step 3: Synthesis of (S)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- To a stirred solution of (S)-1-(2-amino-5-methoxy-4-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)pyrrolidin-3-ol (Step 2, 0.2 g, 0.4 mmol, 1.0 eq) in DCM (5 ml) at 0°C, were added N,N-Diisopropylethylamine (0.16 ml, 0.8 mmol, 2.0 eq) and acryloyl chloride (0.035 ml, 0.4 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for 3 hours. 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 (20 ml) and brine solution (20 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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.033 g, yield: 15.6%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 9.33 (s, 1H), 8.51 (m, 2H), 7.74 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.51 (d, J = 5.0 Hz, 1H), 7.35 (m, 1H), 7.28 (m, 1H), 6.51 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.49 (s, 1H), 6.20 (dd, J = 2.0 Hz, 17.0 Hz, 1H), 5.69 (dd, J = 10.0 Hz, 1H), 4.92 (d, J = 4.0 Hz, 1H), 4.32 (m, 1H), 4.10 (s, 3H).3.80 (s, 3H), 3.45 (m, 1H), 3.40 (m, 1H), 3.19 (m, 1H), 2.99 (m, 1H), 1.99 (m, 1H), 1.80 (m, 1H); Mass m / z: 486.22 (M+H)+. Example 44: Preparation of (R)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1- methyl1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: Step 1: Synthesis of (R)-1-(5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-nitrophenyl)pyrrolidin-3-ol: To a stirred solution of (R)-1-(4-(3-hydroxypyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 30, 1.0 g, 3.1 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.53 g, 1.86 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.6 g, yield: 42.8%) as an off-white solid. Mass m / z: 462.32 (M+H)+. Step 2: Synthesis of (R)-1-(2-amino-5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)pyrrolidin-3-ol: To a stirred solution of (R)-1-(5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-nitrophenyl)pyrrolidin-3-ol (Step 1, 0.5 g, 1.08 mmol, 1.0 eq) in methanol (5 ml) and ethyl acetate (5 ml) was added 10% Pd / C (0.05 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.4 g, yield: 85.6%) was used as such for next step without further purification. Mass m / z: 432.18 (M+H)+. Step 3: Synthesis of (R)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of (R)-1-(2-amino-5-methoxy-4-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)pyrrolidin-3-ol (Step 2, 0.2 g, 0.4 mmol, 1.0 eq) in DCM (5 ml) at 0°C, were added N,N-Diisopropylethylamine (0.16 ml, 0.8 mmol, 2.0 eq) and acryloyl chloride (0.035 ml, 0.4 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for 3 hours. 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 (20 ml) and brine solution (20 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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.040 g, yield: 17.8%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 9.33 (s, 1H), 8.51 (m, 2H), 7.74 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.51 (d, J = 5.0 Hz, 1H), 7.35 (m, 1H), 7.28 (m, 1H), 6.51 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.49 (s, 1H), 6.20 (dd, J = 2.0 Hz, 17.0 Hz, 1H), 5.69 (dd, J = 10.0 Hz, 1H), 4.92 (d, J = 4.0 Hz, 1H), 4.32 (m, 1H), 4.10 (s, 3H).3.80 (s, 3H), 3.45 (m, 1H), 3.40 (m, 1H), 3.19 (m, 1H), 2.99 (m, 1H), 1.99 (m, 1H), 1.80 (m, 1H); Mass m / z: 486.29 (M+H)+. Example 45: Preparation of (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxy-5-((4- (1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of (S)-1-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 26, 1.12 g, 3.5 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.481 g, 2.1 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and 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: 77.3%) as an off-white solid. Mass m / z: 489.31 (M+H)+. Step 2: Synthesis of (S)-4-(3-(dimethylamino)pyrrolidin-1-yl)-6-methoxy-N1-(4-(1-methyl- To a stirred solution of (S)-N-(4-(3-(dimethylamino)pyrrolidin-1-yl)-2-methoxy-5- nitrophenyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine (Step 1, 1.3 g, 2.66 mmol, 1.0 eq) in methanol (13 ml) and ethyl acetate (13 ml) was added 10% Pd / C (0.12 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (80 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (1.0 g, yield: 83.2%) was used as such for next step without further purification. Mass m / z: 459.34 (M+H)+. Step 3: Synthesis of (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl- To a stirred solution of (S)-4-(3-(dimethylamino)pyrrolidin-1-yl)-6-methoxy-N1- (4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,3-diamine (Step 2, 0.5 g, 1.0 mmol, 1.0 eq) in DCM (8 ml) at 0°C, were added N,N-Diisopropylethylamine (0.57 ml, 3.2 mmol, 3.0 eq) and acryloyl chloride (0.088 ml, 1.0 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.22 g, yield: 39.4%) as a pale-yellow solid.1H-NMR (500 MHz-DMSO-d6): 9.38 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 8.50 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 8.0 Hz, 1H), 7.52 (s, 1H), 7.51 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 6.52 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.49 (s, 1H), 6.19 (dd, J = 1.5 Hz, 17.0 Hz, 1H), 5.69 (dd, J = 1.5 Hz, 10.0 Hz, 1H), 4.10 (s, 3H), 3.80 (s, 3H), 3.38 (m, 2H), 3.19 (m, 2H), 2.67 (m, 1H), 2.16 (s, 6H), 2.08 (m, 1H), 1.72 (m, 1H); Mass m / z: 513.51 (M+H)+. Example 46: Preparation of N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)acrylamide: To a stirred solution of 1-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1- yl)-5-nitrophenyl)guanidine (Intermediate 28, 1.7 g, 4.3 mmol, 1.0 eq) in n-butanol (30 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.597 g, 2.5 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.9 g, yield: 37.2%) as an off-white solid. Mass m / z: 558.37 (M+H)+. Step 2: Synthesis of 6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)- To a stirred solution of N-(2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1- yl)-5-nitrophenyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine (Step 1, 0.9 g, 1.6 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (100 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.85 g, yield: 99.8%) was used as such for next step without further purification. Mass m / z: 528.42 (M+H)+. Step 3: Synthesis of N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of 6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)benzene-1,3-diamine (Step 2, 0.85 g, 1.6 mmol, 1.0 eq) in DCM (10 ml) at 0°C, were added N,N-Diisopropylethylamine (0.59 ml, 3.2 mmol, 2.0 eq) and acryloyl chloride (0.137 ml, 1.6 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for 3 hours. 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 (30 ml) and brine solution (20 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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.33 g, yield: 35.2%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 8.96 (s, 1H), 8.62 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.27 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.33 (m, 2H), 6.84 (s, 1H), 6.68 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.21 (dd, J = 1.5 Hz, 17.0 Hz, 1H), 5.73 (dd, J = 1.5 Hz, 10.0 Hz, 1H), 4.08 (s, 3H), 3.79 (s, 3H), 3.07 (m, 2H), 2.72 (m, 3H), 2.54 (m, 2H), 2.28 (m, 6H), 2.15 (s, 3H), 1.87 (m, 2H), 1.73 (m, 2H); Mass m / z: 582.65 (M+H)+. Example 47: Preparation of (R)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide: Step 1: Synthesis of (R)-N-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)-5- nitrophenyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine: To a stirred solution of (R)-1-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin- 1-yl)-5-nitrophenyl)guanidine (Intermediate 31, 1.5 g, 3.9 mmol, 1.0 eq) in n-butanol (30 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.547 g, 2.3 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.9 g, yield: 42.8%) as an off-white solid. Mass m / z: 544.31 (M+H)+. Step 2: Synthesis of (R)-6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of (R)-N-(2-methoxy-4-(3-(4-methylpiperazin-1- yl)pyrrolidin-1-yl)-5-nitrophenyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- amine (Step 1, 0.9 g, 1.65 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (100 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.85 g, yield: 99.8%) was used as such for next step without further purification. Mass m / z: 514.26 (M+H)+. Step 3: Synthesis of (R)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide: To a stirred solution of (R)-6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)benzene-1,3-diamine (Step 2, 0.85 g, 1.6 mmol, 1.0 eq) in DCM (10 ml) at 0 °C, were added N,N-Diisopropylethylamine (0.61 ml, 3.2 mmol, 2.0 eq) and acryloyl chloride (0.13 ml, 1.6 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for 3 hours. 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 (20 ml) and brine solution (20 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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.222 g, yield: 23.6%) as a pale green solid.1H-NMR (500 MHz-DMSO-d6): 9.33 (s, 1H), 8.52 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.52 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 6.51 (s, 1H), 6.48 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.19 (d, 17.0 Hz, 1H), 5.69 (d, J = 10.0 Hz, 1H), 4.10 (s, 3H), 3.80 (s, 3H), 3.38 (m, 2H), 3.16 (m, 2H), 2.79 (m, 1H), 2.63 (m, 2H), 2.36 (m, 6H), 2.14 (s, 3H), 2.10 (m, 1H), 1.71 (m, 1H); Mass m / z: 568.56 (M+H)+. Example 48: Preparation of (S)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide: To a stirred solution of (S)-1-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin- 1-yl)-5-nitrophenyl)guanidine (Intermediate 27, 1.98 g, 5.2 mmol, 1.0 eq) in n-butanol (40 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1- one (Intermediate 1, 0.721 g, 3.1 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (2.4 g, yield: 84.2%) as an off-white solid. Mass m / z: 544.03 (M+H)+. Step 2: Synthesis of (S)-6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- To a stirred solution of (S)-N-(2-methoxy-4-(3-(4-methylpiperazin-1-yl)pyrrolidin- 1-yl)-5-nitrophenyl)-4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine (Step 1, 2.4 g, 4.4 mmol, 1.0 eq) in methanol (25 ml) and ethyl acetate (25 ml) was added 10% Pd / C (0.25 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (150 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (1.8 g, yield: 79.6%) was used as such for next step without further purification. Mass m / z: 514.16 (M+H)+. Step 3: Synthesis of (S)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin- To a stirred solution of (S)-6-methoxy-N1-(4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)-4-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)benzene-1,3-diamine (Step 2, 1.8 g, 3.5 mmol, 1.0 eq) in DCM (20 ml) at 0°C, were added N,N-Diisopropylethylamine (1.29 ml, 7.0 mmol, 2.0 eq) and acryloyl chloride (0.28 ml, 3.5 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (150 ml) and washed with water (50 ml) and brine solution (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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.6 g, yield: 30.1%) as a orange solid.1H-NMR (500 MHz-DMSO-d6): 9.33 (s, 1H), 8.52 (s, 1H), 8.51 (d, J = 5.0 Hz, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.52 (d, J = 5.0 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.28 (t, J = 8.0 Hz, 1H), 6.51 (s, 1H), 6.48 (dd, J = 10.0 Hz, 17.0 Hz, 1H), 6.19 (d, 17.0 Hz, 1H), 5.69 (d, J = 10.0 Hz, 1H), 4.10 (s, 3H), 3.80 (s, 3H), 3.38 (m, 2H), 3.16 (m, 2H), 2.79 (m, 1H), 2.63 (m, 2H), 2.36 (m, 6H), 2.14 (s, 3H), 2.10 (m, 1H), 1.71 (m, 1H); Mass m / z: 568.17 (M+H)+. Example 49: Preparation of N-(2-(4-ethylpiperazin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: Step 1: Synthesis of N-(4-(4-ethylpiperazin-1-yl)-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-amine: To a stirred solution of 1-(4-(4-ethylpiperazin-1-yl)-2-methoxy-5- nitrophenyl)guanidine (Intermediate 32, 1.1 g, 3.4 mmol, 1.0 eq) in n-butanol (20 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.47 g, 2.0 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 0-3% methanol in dichloromethane gradient to obtain the title compound (0.7 g, yield: 43.7%) as an off-white solid. Mass m / z: 489.14 (M+H)+. Step 2: Synthesis of 4-(4-ethylpiperazin-1-yl)-6-methoxy-N1-(4-(1-methyl-1H- To a stirred solution of N-(4-(4-ethylpiperazin-1-yl)-2-methoxy-5-nitrophenyl)-4- (1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-amine (Step 1, 0.7 g, 1.43 mmol, 1.0 eq) in methanol (7 ml) and ethyl acetate (7 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (60 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.5 g, yield: 76.0%) was used as such for next step without further purification. Mass m / z: 459.36 (M+H)+. Step 3: Synthesis of N-(2-(4-ethylpiperazin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- To a stirred solution of 4-(4-ethylpiperazin-1-yl)-6-methoxy-N1-(4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,3-diamine (Step 2, 0.5 g, 1.1 mmol, 1.0 eq) in DCM (8 ml) at 0°C, were added N,N-Diisopropylethylamine (0.41 ml, 2.2 mmol, 2.0 eq) and acryloyl chloride (0.099 ml, 1.1 mmol, 1.0 eq). The reaction mixture was allowed to room temperature and stirred for 3 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with DCM (30 ml) and washed with water (20 ml) and brine solution (20 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 0-3% methanol in dichloromethane gradient to obtain the title compound (0.158 g, yield: 28.2%) as a pale-yellow solid.1H-NMR (500 MHz-DMSO-d6): 8.99 (s, 1H), 8.63 (s, 1H), 8.55 (d, J = 5.0 Hz, 1H), 8.25 (s, 1H), 7.74 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 5.0 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 6.88 (s, 1H), 6.61 (dd, J = 10.5 Hz, 17.0 Hz, 1H), 6.20 (d, J = 17.0 Hz, 1H), 5.72 (d, J = 10.5 Hz, 1H), 4.09 (s, 3H), 3.81 (s, 3H), 2.88 (m, 4H), 2.58 (m, 4H), 2.42 (q, J = 7.0 Hz, 2H), 1.04 (t, J = 7.0 Hz, 3H); Mass m / z: 513.43 (M+H)+. Example 50: Preparation of N-(4-methoxy-2-((2-methoxyethyl)(methyl)amino)-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide: To a stirred solution of 1-(2-methoxy-4-((2-methoxyethyl)(methyl)amino)-5- nitrophenyl)guanidine (Intermediate 33, 1.59 g, 5.0 mmol, 1.0 eq) in n-butanol (30 ml) was added (E)-3-(dimethylamino)-1-(1-methyl-1H-benzo[d]imidazol-2-yl)prop-2-en-1-one (Intermediate 1, 0.693 g, 3.0 mmol, 0.6 eq). The reaction mixture was heated to 100oC for 28 hours. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was evaporated under reduced pressure and the crude compound was purified by silica gel column chromatography using 2% methanol in dichloromethane gradient to obtain the title compound (1.2 g, yield: 48.4%) as an off-white solid. Mass m / z: 464.24 (M+H)+. Step 2: Synthesis of 5-methoxy-N1-(2-methoxyethyl)-N1-methyl-N4-(4-(1-methyl-1H- To a stirred solution of 2-methoxy-N4-(2-methoxyethyl)-N4-methyl-N1-(4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)-5-nitrobenzene-1,4-diamine (Step 1, 1.0 g, 2.1 mmol, 1.0 eq) in methanol (10 ml) and ethyl acetate (10 ml) was added 10% Pd / C (0.1 g, 50% wet). 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 pad and washed with methanol and ethyl acetate (50 ml, 1:1). The filtrate was evaporated under reduced pressure and the obtained compound (0.92 g, yield: 98%) was used as such for next step without further purification. Mass m / z: 434.27 (M+H)+. Step 3: Synthesis of N-(4-methoxy-2-((2-methoxyethyl)(methyl)amino)-5-((4-(1-methyl-1H- To a stirred solution of 5-methoxy-N1-(2-methoxyethyl)-N1-methyl-N4-(4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)benzene-1,2,4-triamine (Step 2, 0.9 g, 1.0 mmol, 1.0 eq) in DCM (10 ml) at 0°C, were added N,N-Diisopropylethylamine (0.6 ml, 3.1 mmol, 3.0 eq) and acryloyl chloride (0.08 ml, 1.0 mmol, 1.0 eq). The reaction mixture was allowed to room temperatur...

Claims

We Claim:

1. A compound of formula (I):Formula (I) wherein, ‘X’ is selected from substituted or unsubstituted heterocyclyl, -N(Ra)(Rb) or - ORa; wherein the substituents are selected from C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, heterocyclyl, -N(Ra)(Rb), hydroxyl, halo, cyano, amino or nitro; R1 is selected from one or more hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, C1-C6 alkoxy, hydroxyl, hydroxylalkyl, halo, cycloalkyloxy, cyano, nitro or amino; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, -C(O)-alkyl, -C(O)-aryl -S(O)2-alkyl, S(O)2-N(Ra)(Rb), -S(O)2-aryl, or hydroxylalkyl; R3 is selected from one or more C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxy or nitro; R4 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 deuteroalkyl, -C(O)-alkyl or -C(O)(O)-alkyl; wherein the substituents are selected from C1-C6 alkoxy, halo, cyano or amino; R5 is selected form C1-C6 alkyl, C2-C6 alkenyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1- C6 alkoxy or cycloalkyloxy; Raand Rbare independently selected from hydrogen, substituted or unsubstituted C1- C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted cycloalkyloxy or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are selected from C1-C6 alkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxyl, or C1-C6 alkylamino; ‘m’ is an integer selected from 1, 2, 3 or 4; and‘n’ is an integer selected from 0, 1, or 2; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof.

2. The compound according to claim 1, which is a compound of the formula (IA):wherein, ‘X’ is selected from substituted or unsubstituted heterocyclyl, -N(Ra)(Rb) or -ORa; wherein the substituents are selected from C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, heterocyclyl, -N(Ra)(Rb), hydroxyl, halo, cyano, amino or nitro; R1 is selected from one or more hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, C1-C6 alkoxy, hydroxyl, hydroxylalkyl, halo, cycloalkyloxy, cyano, nitro or amino; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, -C(O)-alkyl, -C(O)-aryl -S(O)2-alkyl -S(O)2-aryl, or hydroxylalkyl; R4 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 deuteroalkyl, -C(O)-alkyl or -C(O)(O)-alkyl; wherein the substituents are selected from C1-C6 alkoxy, halo, cyano or amino; R5 is selected form C1-C6 alkyl, C2-C6 alkenyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1- C6 alkoxy or cycloalkyloxy; Ra and Rb are independently selected from hydrogen, substituted or unsubstituted C1- C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted cycloalkyloxy or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are selected from C1-C6 alkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxyl or C1-C6 alkylamino; and ‘m’ is an integer selected from 1, 2, 3 or 4; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof.

3. The compound according to claim 1, which is a compound of the formula (IB):wherein, R1 is selected from one or more hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6cycloalkyl, substituted or unsubstituted C1-C6haloalkyl, C1-C6 alkoxy, hydroxyl, hydroxylalkyl, halo, cycloalkyloxy, cyano, nitro or amino; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, -C(O)-alkyl, -C(O)-aryl -S(O)2-alkyl -S(O)2-aryl, or hydroxylalkyl; R4 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 deuteroalkyl, -C(O)-alkyl or -C(O)(O)-alkyl; wherein the substituents are selected from C1-C6 alkoxy, halo, cyano or amino; R5 is selected form C1-C6 alkyl, C2-C6 alkenyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1- C6 alkoxy or cycloalkyloxy; Raand Rbare independently selected from hydrogen, substituted or unsubstituted C1- C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted cycloalkyloxy or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are selected from C1-C6 alkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxyl, or C1-C6 alkylamino; and ‘m’ is an integer selected from 1, 2, 3 or 4; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof.

4. The compound according to claim 1, which is a compound of the formula (IC):wherein, R1 is selected from one or more hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, C1-C6alkoxy, hydroxyl, hydroxylalkyl, halo, cycloalkyloxy, cyano, nitro or amino; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, -C(O)-alkyl, -C(O)-aryl -S(O)2-alkyl -S(O)2-aryl, or hydroxylalkyl; Ra and Rb are independently selected from hydrogen, substituted or unsubstituted C1- C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted cycloalkyloxy or substituted or unsubstituted heterocyclylalkyl; wherein the substituents are selected from C1-C6 alkyl, C1-C6 alkoxy, halo, cyano, amino, hydroxyl, or C1-C6 alkylamino; and ‘m’ is an integer selected from 1, 2, 3 or 4; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof.

5. The compound according to claim 1, which is a compound of the formula (ID):wherein, R1 is selected from one or more hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C1-C6 haloalkyl, C1-C6alkoxy, hydroxyl, hydroxylalkyl, halo, cycloalkyloxy, cyano, nitro or amino; R2 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, C1-C6 deuteroalkyl, C1-C6 haloalkyl, -C(O)-alkyl, -C(O)-aryl -S(O)2-alkyl -S(O)2-aryl, or hydroxylalkyl; and ‘m’ is an integer selected from 1, 2, 3 or 4; or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof.

6. A compound is selected from the group consisting ofN-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propenamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propionamide, N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- morpholinophenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acetamide, N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)acrylamide, 3-chloro-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-morpholinophenyl)propenamide, 3-chloro-N-(2-(4-hydroxypiperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propenamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-5-((4-(5-fluoro-1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, (S)-N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 4-methoxy-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide, N-(5-((4-(5-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxy-2-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)acrylamide, N-(4-methoxy-2-(methyl(2-morpholinoethyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-((2- (dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-5- (trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1-methyl- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)propenamide,3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-5-(trifluoromethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)phenyl)propenamide, N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, 3-chloro-N-(5-((4-(5,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)propenamide, 3-chloro-N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)propenamide, 2-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acetamide, N-(2-((2-(1,1-dioxidothiomorpholino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-hydroxyethyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(6-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-7-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-ethyl-5-fluoro-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-isopropyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(6-chloro-4-fluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((3-(dimethylamino)propyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(diethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide,N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((3-(dimethylamino)propyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, 3-chloro-N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)propenamide, N-(5-((4-(5,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, (S)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, (R)-N-(2-(3-hydroxypyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, (S)-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- (4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)acrylamide, (R)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide, (S)-N-(4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-(3-(4-methylpiperazin-1-yl)pyrrolidin-1-yl)phenyl)acrylamide,N-(2-(4-ethylpiperazin-1-yl)-4-methoxy-5-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(4-methoxy-2-((2-methoxyethyl)(methyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, tert-butyl (2-((2-acrylamido-5-methoxy-4-((4-(1-methyl-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)phenyl)(methyl)amino)ethyl)(methyl)carbamate, N-(4-methoxy-2-(methyl(2-(methylamino)ethyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5-chloro-7-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide, N-(5-((4-(6-chloro-4-fluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4- methoxyphenyl)acrylamide, N-(5-((4-(5-chloro-1-ethyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2- ((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(methyl-d3)-1H-benzo[d]imidazol-2-yl)pyrimidin-2- yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(1-(methyl-d3)- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2,2,2- trifluoroethoxy)phenyl)acrylamide, N-(5-((4-(5,7-difluoro-1-methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)- 2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2,2,2-trifluoroethoxy)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2,2,2-trifluoroethoxy)-5-((4-(1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-(2,2,2-trifluoroethoxy)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2-methoxyethoxy)-5-((4-(1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide,N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2-methoxyethoxy)-5-((4-(1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(methoxy-d3)-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(5-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(5-((4-(6-chloro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(5-fluoro-1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxyphenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(6-fluoro-1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4- methoxyphenyl)acrylamide, N-(2-(4-(dimethylamino)piperidin-1-yl)-4-methoxy-5-((4-(1-(2,2,2- trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-(4-(dimethylamino)piperidin-1-yl)-4-methoxy-5-((4-(1-methyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2- yl)pyrimidin-2-yl)amino)-4-methoxy-2-(4-methylpiperazin-1-yl)phenyl)acrylamide, N-(4-methoxy-2-(4-methylpiperazin-1-yl)-5-((4-(1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(5-((4-(4,6-difluoro-1-(2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin- 2-yl)amino)-2-(3-(dimethylamino)azetidin-1-yl)-4-methoxyphenyl)acrylamide, N-(2-(3-(dimethylamino)azetidin-1-yl)-4-methoxy-5-((4-(1-(2,2,2-trifluoroethyl)- 1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1- methyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-5-((4-(1-ethyl-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-4-methoxyphenyl)acrylamide, N-(2-(2-(dimethylamino)ethoxy)-4-methoxy-5-((4-(1-(2,2,2-trifluoroethyl)-1H- benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide,N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(5-methoxy-1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-methoxy-5-((4-(6-methoxy-1- (2,2,2-trifluoroethyl)-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)phenyl)acrylamide, and N-(5-((4-(1-cyclobutyl-1H-benzo[d]imidazol-2-yl)pyrimidin-2-yl)amino)-2-(4- (dimethylamino)piperidin-1-yl)-4-methoxyphenyl)acrylamide, or pharmaceutically acceptable salts, pharmaceutically acceptable stereoisomers, or pharmaceutically acceptable prodrugs, or pharmaceutically active metabolites or N-oxides or a combination thereof.

7. A pharmaceutical composition comprising a compound according to any one of claims 1-6 and at least one pharmaceutically acceptable excipient.

8. The pharmaceutical composition according to claim 7, wherein the pharmaceutically acceptable excipient is a carrier or a diluent.

9. A method of treating cancer, the method comprising administering to a subject an effective amount of a compound of Formula (I) according to any one of claims 1-6 or a pharmaceutical composition thereof.

10. The method according to claim 9, wherein the cancer is non-small cell lung cancer.

11. The method according to claim 9, wherein the cancer is selected from the group consisting of multiple myeloma, melanoma, acute myeloid leukemia (AML), anaplastic large cell lymphoma, renal cancer, endometrial cancer, thyroid cancer, cholangiocarcinoma, gastrointestinal stromal tumor (GIST), gastric cancer, lung cancer, hepatocellular carcinoma, non-Hodgkin lymphoma, gastric cancer, ovarian cancer, cervical cancer, colorectal cancer, pancreatic cancer, glioma, glioblastoma, breast cancer, prostate cancer, leukemia and lymphoma.

12. A method of treating cancer, the method comprising administering to a subject in need thereof the pharmaceutical composition according to claim 7.

13. The method according to claim 12, wherein the cancer is non-small cell lung cancer.

14. The method according to claim 12, wherein the cancer is selected from the group consisting of multiple myeloma, melanoma, acute myeloid leukemia (AML), anaplastic large cell lymphoma, renal cancer, endometrial cancer, thyroid cancer, cholangiocarcinoma, gastrointestinal stromal tumor (GIST), gastric cancer, lung cancer, hepatocellular carcinoma, non-Hodgkin lymphoma, gastric cancer, ovarian cancer, cervical cancer,colorectal cancer, pancreatic cancer, glioma, glioblastoma, breast cancer, prostate cancer, leukemia and lymphoma.

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