Quinazolinone compounds for treatment of hbv

Abstract

The present disclosure is directed to novel compounds, salts thereof, compositions, and methods of using as well as synthesizing. The present disclosure is directed, at least in part, to compounds for the treatment of Hepatitis B (HBV) infection and compositions prepared therefrom. Methods of making and using the compounds for the treatment of Hepatitis B (HBV) infection are also provided.

Description

QUINAZOLINONE COMPOUNDS FOR TREATMENT OF HBVCROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of priority of U.S. Provisional Application No. 63 / 563,750, filed March 11, 2024, the contents of which are hereby incorporated by reference in its entirety.FIELD

[0002] The present disclosure relates to novel compounds for the treatment of Hepatits B (HBV) as well as methods of making and using the compounds.BACKGROUND

[0003] Hepatitis B (HBV) causes viral hepatitis that can further lead to chronic liver disease and increase the risk of liver cirrhosis and liver cancer (hepatocellular carcinoma). Worldwide, about 2 billion people have been infected with HBV, around 360 million people are chronically infected, and every year HBV infection causes more than one half million deaths. HBV can be spread by body fluids: from mother to child, by sex, and via blood products. Children bom to HBV-positive mothers may also be infected, unless vaccinated at birth.

[0004] The hepatitis virus particle is composed of a lipid envelope studded with surface protein (HBsAg) that surrounds the viral core. The core is composed of a protein shell, or capsid, built of 120 core protein (Cp) dimers, which in turn contains the relaxed circular DNA (rcDNA) viral genome as well as viral and host proteins. In an infected cell, the genome is found as a covalently closed circular DNA (cccDNA) in the host cell nucleus. The cccDNA is the template for viral RNAs and thus viral proteins. In the cytoplasm, Cp assembles around a complex of full-length viral RNA (the so-called pregenomic RNA or pgRNA and viral polymerase (P). After assembly, P reverse transcribes the pgRNA to rcDNA within the confines of the capsid to generate the DNA- filled viral core.

[0005] At present, chronic HBV is primarily treated with nucleos(t)ide analogs (e.g., entecavir) that suppress the vims while the patient remains on treatment, but do not eliminate the infection, even after many years of treatment. Once a patient stalls taking nucleos(t)ide analogs, most mustcontinue taking them or risk the possibility of a life-threatening immune response due to viral rebound. Further, nucleotide therapy may lead to the emergence of antiviral drug resistance.

[0006] The only FDA approved alternative to nucleos(t)ide analogs is treatment with interferon a or pegylated interferon a. Unfortunately, the adverse event incidence and profile of interferon a can result in poor tolerability, and many patients are unable to complete therapy. Moreover, only a small percentage of patients are considered appropriate for interferon therapy, as only a small subset of patients are likely to have a sustained clinical response to a course of interferon therapy. As a result, interferon-based therapies are used in only a small percentage of all diagnosed patients who elect treatment.

[0007] Thus, current HBV treatments can range from palliative to watchful waiting. Nucleotide analogs suppress virus production, treating the symptom, but leave the infection intact. Interferon a has severe side effects and less tolerability among patients and is successful as a finite treatment strategy in only a small minority of patients. There is a clear on-going need for more effective treatments for HBV infections.BRIEF SUMMARY OF THE DISCLOSURE

[0008] One embodiment of the disclosure relates to a c compound of Formula Ior a pharmaceutically acceptable salt thereof, wherein:X1is S, O, NRc;R1is -C1-4alkylC(O)OH, -C1-4alkylC(O)OC1-4alkyl, -OC1-4alkyleneC(O)OC1-4alkyl, -C1-4alkylC(O)NRcRd,R2is, SC1-6alkyl, SC1-4alkylene, SC1-4alkylR13, SC1-4alkylN(Ra)(Rb), or =S;R13is selected from the group consisting of hydrogen, halogen, OH, C(O)OH, - C(O)NRcRd, C(O)OC1-4alkyl, cyclohexyl, morpholinyl, phenyl, indole, pyrrolidine, pyridyl ;R3is absent or hydrogen;Raand Rbare independently selected from the group consisting of hydrogen, CN, C1-4alkyl and C2-4alkenyl; each of R4, R5, R6, and R7is independently selected from the group consisting of hydrogen, halogen, NO2, CN, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, OC1-4alkylene-R14, guanidinyl and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, NRcRd, C1-4alkyl, C(O)OH, C(O)OC1-4alkyl, OC1-4alkyl, C(O)NRcRd, OC(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo;R8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C1-4alkyl, C1-4haloalkyl, NHC(O)C1-4alkyl, OC1-4alkyl, C(O)OH, C(O)OC1-4alkyl, C(O)NRcRd, S(O)qNRcRd, NHC(O)NRcRd, guanidinyl, NHCN(C(O)O- tertbutyl)N(H)C(O)O-tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;R18is hydrogen, C1-4alkyl, C(O)OC1-4alkyl or S(O)qNRcRd;Rcand Rdare independently selected for each occurrence from the group consisting of hydrogen, C1-4alkyl, C1-4haloalkyl C3-6monocycloalkyl, and C(O)OC1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

[0009] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein

[0010] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, S(O)qC1-4alkyl, OC1-4alkyl-R14, and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, C(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo.

[0011] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein two of R4, R5, R6, and R7are hydrogen.

[0012] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein three of R4, R5, R6, and R7are hydrogen.

[0013] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are halo.

[0014] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are Br.

[0015] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are OC1-4alkyl-R14.

[0016] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are -OCH3.

[0017] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R3is H.

[0018] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R3is absent.

[0019] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein R1is

[0020] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein three of R8, R9, R10, R11and R12are hydrogen.

[0021] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein four of R8, R9, R10, R11and R12are hydrogen.

[0022] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R8, R9, R10, R11and R12are halo.

[0023] In some aspects, the disclosure relates to a compound of Formula (I), or a pharmaceutically acceptable salt thereof, wherein one of R8, R9, R10, R11and R12are Cl.

[0024] In some embodiments, the disclosure relates to a compound of Formula II(II), or a pharmaceutically acceptable salt thereof, wherein:X1is S, O, NRc;R1is -C1-4alkylC(O)OH, -C1-4alkylC(O)OC1-4alkyl, -OC1-4alkyleneC(O)OC1-4alkyl, -C1-4alkylC(O)NRcRd,R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, CN, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, OC1-4alkylene-R14, guanidinyl and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, NRcRd, C1-4alkyl, C(O)OH, C(O)OC1-4alkyl, OC1-4alkyl, C(O)NRcRd, OC(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo;R8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C1-4alkyl, CMhaloalkyl, NHC(O)C1-4alkyl, OC1-4alkyl, C(O)OH, C(O)OC1-4alkyl, C(O)NRcRd, S(O)qNRcRd, NHC(O)NRcRd, guanidinyl, NHCN(C(O)O- tertbutyl)N(H)C(O)O-tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17;L1is a bond or -S(O)q-;R18is hydrogen, C1-4alkyl, C(O)OC1-4alkyl or S(O)qNRcRd;Rcand Rdare independently selected for each occurrence from the group consisting of hydrogen, C1-4alkyl, C1-4haloalkyl C3-6monocycloalkyl, and C(O)OC1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

[0025] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein

[0026] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, NRcRd, C1-4alkyl, C(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo.

[0027] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein two of R4, R5, R6, and R7are hydrogen.

[0028] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein three of R4, R5, R6, and R7are hydrogen.

[0029] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are halo.

[0030] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are Br.

[0031] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are OC1-4alkyl-R14.

[0032] In some aspects, the disclosure relates to a compound of Formula (II), or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are -OCH3.

[0033] In some embodiments, the disclosure relates to a compound of Formula IIIor a pharmaceutically acceptable salt thereof, whereinR8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NRcRd, C1-4haloalkyl, C(O)NRcRd, S(O)qNRcRd, NHCN(C(O)O-tertbutyl)N(H)C(O)O- tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;Reand Rdare independently selected for each occurrence from the group consisting of hydrogen and C1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

[0034] In some aspects, the disclosure relates to a pharmaceutical composition comprising a compound of Formulas (I), (II), or (III), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

[0035] In some embodiments, the disclosure relates to a method of treating Hepatitis B (HB V) infection in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a compound of the disclosure, or a pharmaceutically acceptable salt thereof.

[0036] In some embodiments, the disclosure relates to a method of treating Hepatitis B (HBV) infection in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition of the disclosure.DETAILED DESCRIPTION OF THE DISCLOSURE

[0037] The present disclosure is directed to compounds and salts thereof, compositions, and methods. The present disclosure is directed, at least in part, to compounds for the treatment of Hepatitis B (HBV) infection and compositions prepared therefrom. Methods of making and using the compounds for the treatment of Hepatitis B (HBV) infection are also provided.Definitions

[0038] The features and other details of the disclosure will now be more particularly described. Before further description of the present disclosure, certain terms employed in the specification, examples and appended claims are collected here. These definitions should be read in light of the remainder of the disclosure and as understood by a person of skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the ait.

[0039] The term “alkenyl” as used herein refers to an unsaturated straight or branched hydrocarbon having at least one carbon-carbon double bond. Exemplary alkenyl groups include, but are not limited to, a straight or branched group of 2-6 carbon atoms, referred to herein as C2-6alkenyl. Exemplary alkenyl groups include, but are not limited to, vinyl, allyl, butenyl, and pentenyl, etc.

[0040] The term “alkoxy” as used herein refers to a straight or branched alkyl group attached to oxygen (i.e., alkyl-O-). Exemplary alkoxy groups include, but are not limited to, alkoxy groups of 1-6 or 1-4 carbon atoms, referred to herein as C1-6alkoxy and C1-6alkoxy, respectively. Exemplary alkoxy groups include, but are not limited to methoxy, ethoxy, and isopropoxy, etc.

[0041] The term “alkoxyalkyl” as used herein refers to an alkyl group substituted with an alkoxy group. Examples include, but are not limited to, -CH2OCH2CH3, -CH2CH2OCH3and -CH2OCH3, etc.

[0042] The term “alkyl” as used herein refers to a saturated straight or branched hydrocarbon. Exemplary alkyl groups include, but are not limited to, straight or branched hydrocarbons of 1-6 or 1-4 carbon atoms, referred to herein as C1-6alkyl and C1-4alkyl, respectively. Exemplary alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-l -butyl, 3- methyl-2-butyl, 2-methyl-l -pentyl, 3-methyl-l -pentyl, 4-methyl-l -pentyl, 2-methyl-2-pentyl, 3- methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-l -butyl, 3,3-dimethyl-l-butyl, 2-ethyl-l -butyl,n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, neopentyl, and n-hexyl, etc. The term “alkylene” as used herein refers to a biradical alkyl group.

[0043] The term “alkynyl” as used herein refers to an unsaturated straight or branched hydrocarbon having at least one carbon-carbon triple bond. Exemplary alkynyl groups include, but are not limited to, straight or branched groups of 2-6 carbon atoms, referred to herein as C2-6alkynyl. Exemplary alkynyl groups include, but are not limited to, ethynyl, propynyl, butynyl, pentynyl, hexynyl, and methylpropynyl, etc.

[0044] The term “cyano” as used herein refers to the radical -CN.

[0045] The term “cycloalkyl” as used herein refers to a saturated monocyclic hydrocarbon group of, for example, 3-6 carbons, referred to herein as C3-6monocycloalkyl, or bicyclic hydrocarbon ring structure of, for example, 8-12 carbons, referred to herein as C8- 12bicycloalkyl. For bicyclic cycloalkyl groups, the two rings may be attached through the same or different carbons. Exemplary monocyclic cycloalkyl groups include, but are not limited to, cyclohexyl, cyclopcntyl, cyclopcntcnyl, cyclobutyl and cyclopropyl. Exemplary bicyclic cycloalkyl groups include, but are not limited to, spiro[2.5]octanyl, spiro[3.5]nonanyl, bicyclo[2.2.2]octanyl, bicyclo[4.1.0]heptanyl, octahydropentalenyl, bicyclo[4.2.0]octanyl, bicyclo[l.l.l]pentanyl, bicyclo[2.2.1]heptanyl, and bicyclo[2.2.2]octanyl.

[0046] The terms “halo” or “halogen” as used herein refer to F, Cl, Br or I.

[0047] The term “haloalkyl” as used herein refers to an alkyl group substituted with one or more halogen atoms. For example, haloC1-6alkyl refers to a straight or branched alkyl group of 1- 6 carbon atoms substituted with one or more halogen atoms. Examples include, but are not limited to, -FCH2, -CI2CH, -F2CH, -CF3, -CH2CF3, -CF2CH3, -CI2CCF3, and -CF2CF3.

[0048] The term “haloalkoxy” as used herein refers to an alkoxy group substituted with one or more halogen atoms. Examples include, but are not limited to, -OCCI3, -OCF3, -OCH2CF3-OCHF2, and -OCF2CF3.

[0049] The terms “hydroxy” and “hydroxyl” as used herein refers to the radical -OH.

[0050] The term “hydroxyalkyl” as used herein refers to an alkyl group substituted with one or more hydroxy groups. Examples include, but are not limited to, -CH2OH, -CH2CH2OH, -CH2CH(OH)CH3and -CH2(OH)CHCH2OH.

[0051] The term “hydro xyalkoxy” as used herein refers to an alkoxy group substituted with one or more hydroxy groups. Examples include but are not limited to -OCH2OH, -OCH2CH2OH, -OCH2(OH)CHCH3and -OCH2(OH)CHCH2OH.

[0052] The term “oxo” as used herein refers to the radical =O.

[0053] The terms “Individual,” “patient,” or “subject” are used interchangeably and include any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans. The compounds or pharmaceutical compositions of the disclosure can be administered to a mammal, such as a human, but can also be administered to other mammals such as an animal in need of veterinary treatment, e.g., domestic animals (e.g., dogs, cats, and the like), farm animals (e.g., cows, sheep, pigs, horses, and the like) and laboratory animals (e.g., rats, mice, guinea pigs, dogs, primates, and the like). The mammal treated in the methods of the disclosure is desirably a mammal in which treatment of HBV infection is desired.

[0054] The term “modulation” includes antagonism (e.g., inhibition), agonism, partial antagonism and / or partial agonism.

[0055] The term “Pharmaceutically acceptable” include molecular entities and compositions that do not produce an adverse, allergic or other untoward reaction when administered to an animal, or a human, as appropriate. For human administration, preparations should meet sterility, pyrogenicity, and general safety and purity standards as required by FDA Office of Biologies standards.

[0056] The term “pharmaceutically acceptable carrier” or “pharmaceutically acceptable excipient” as used herein refers to any and all solvents, dispersion media, coatings, isotonic and absorption delaying agents, fillers, and the like, that are compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. The compositions may also contain other active compounds providing supplemental, additional, or enhanced therapeutic functions.

[0057] The term “pharmaceutical composition” as used herein refers to a composition comprising at least one compound as disclosed herein formulated together with one or more pharmaceutically acceptable excipients.

[0058] The term "pharmaceutically acceptable salt(s)" as used herein refers to salts of acidic or basic groups that may be present in compounds used in the compositions. Compounds includedin the present compositions that are basic in nature are capable of forming a wide variety of salts with various inorganic and organic acids. The acids that may be used to prepare pharmaceutically acceptable acid addition salts of such basic compounds are those that form non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions, including, but not limited to, malate, oxalate, chloride, bromide, iodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate (i.e., 1, 1'-methylene-bis-(2-hydroxy-3-naphthoate)) salts. Compounds included in the present compositions that are acidic in nature are capable of forming base salts with various pharmacologically acceptable cations. Examples of such salts include alkali metal or alkaline earth metal salts, particularly calcium, magnesium, sodium, lithium, zinc, potassium, and iron salts. Compounds included in the present compositions that include a basic or acidic moiety may also form pharmaceutically acceptable salts with various amino acids. The compounds of the disclosure may contain both acidic and basic groups; for example, one amino and one carboxylic acid group. In such a case, the compound can exist as an acid addition salt, a zwitterion, or a base salt.

[0059] The term “therapeutically effective amount” or “effective amount” as used herein refers to the amount of the subject compound that will elicit the biological or medical response of a tissue, system or animal, (e.g., mammal or human) that is being sought by the researcher, veterinarian, medical doctor or other clinician. The compounds or pharmaceutical compositions of the disclosure are administered in therapeutically effective amounts to treat a disease. Alternatively, a therapeutically effective amount of a compound is the quantity required to achieve a desired therapeutic and / or prophylactic effect.

[0060] The term “treating” includes any effect, e.g., lessening, reducing, modulating, or eliminating, via disruption of HBV core protein assembly, that results in the improvement of the disease. “Disruption” includes inhibition of HBV viral assembly and infection.

[0061] The compounds of the disclosure may contain one or more chiral centers and, therefore, exist as stereoisomers. The term “stereoisomers” when used herein consist of all enantiomers or diastereomers. These compounds may be designated by the symbols “(+),” "(-)," “R” or “S,” depending on the configuration of substituents around the stereogenic carbon atom, but the skilled artisan will recognize that a structure may denote a chiral center implicitly. The present disclosureencompasses various stereoisomers of these compounds and mixtures thereof. Mixtures of enantiomers or diastereomers may be designated “(+)” in nomenclature, but the skilled artisan will recognize that a structure may denote a chiral center implicitly.

[0062] The compounds of the disclosure may contain one or more double bonds and, therefore, exist as geometric isomers resulting from the arrangement of substituents around a carbon-carbon double bond. The symboldenotes a bond that may be a single, double or triple bond as described herein. Substituents around a carbon-carbon double bond are designated as being in the “Z’ or “E” configuration wherein the terms “Z" and “E” are used in accordance with IUPAC standards. Unless otherwise specified, structures depicting double bonds encompass both the“E” and “Z” isomers. Substituents around a carbon-carbon double bond alternatively can be referred to as “cis” or “trans,” where “cis” represents substituents on the same side of the double bond and “trans” represents substituents on opposite sides of the double bond.

[0063] Compounds of the disclosure may contain a carbocyclic or heterocyclic ring and therefore, exist as geometric isomers resulting from the arrangement of substituents around the ring. The arrangement of substituents around a carbocyclic or heterocyclic ring are designated as being in the “Z” or “E” configuration wherein the terms “Z” and “E” are used in accordance with IUPAC standards. Unless otherwise specified, structures depicting carbocyclic or heterocyclic rings encompass both “Z” and “E” isomers. Substituents around a carbocyclic or heterocyclic ring may also be referred to as “cis” or “trans”, where the term “cis” represents substituents on the same side of the plane of the ring and the term “trans” represents substituents on opposite sides of the plane of the ring. Mixtures of compounds wherein the substituents are disposed on both the same and opposite sides of plane of the ring are designated “cis / trans.”

[0064] Individual enantiomers and diastereomers of compounds of the present disclosure can be prepared synthetically from commercially available starting materials that contain asymmetric or stereogenic centers, or by preparation of racemic mixtures followed by resolution methods well known to those of ordinary skill in the art. These methods of resolution are exemplified by (1) attachment of a mixture of enantiomers to a chiral auxiliary, separation of the resulting mixture of diastereomers by recrystallization or chromatography and liberation of the optically pure product from the auxiliary, (2) salt formation employing an optically active resolving agent, (3) direct separation of the mixture of optical enantiomers on chiral liquid chromatographic columns or (4) kinetic resolution using stereoselective chemical or enzymatic reagents. Racemic mixtures can alsobe resolved into their component enantiomers by well-known methods, such as chiral-phase liquid chromatography or crystallizing the compound in a chiral solvent. Stereoselective syntheses, a chemical or enzymatic reaction in which a single reactant forms an unequal mixture of stereoisomers during the creation of a new stereocenter or during the transformation of a preexisting one, are well known in the art. Stereoselective syntheses encompass both enantiomeric and diastereoselective transformations and may involve the use of chiral auxiliaries. For examples, see Carreira and Kvaerno, Classics in Stereoselective Synthesis, Wiley-VCH: Weinheim, 2009.

[0065] The compounds disclosed herein can exist in solvated as well as unsolvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like, and it is intended that the disclosure embrace both solvated and unsolvated forms. In one embodiment, the compound is amorphous. In one embodiment, the compound is a single polymorph. In another embodiment, the compound is a mixture of polymorphs. In another embodiment, the compound is in a crystalline form.

[0066] The disclosure also embraces isotopically labeled compounds of the disclosure which are identical to those recited herein, except that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes that can be incorporated into compounds of the disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine, such as2H,3H,13C,14C,15N,18O,17O,31P,32P,35S,18F, and36Cl, respectively. For example, a compound of the disclosure may have one or more H atom replaced with deuterium.

[0067] Certain isotopically-labeled disclosed compounds (e.g., those labeled with3H and14C) are useful in compound and / or substrate tissue distribution assays. Tritiated (i.e.,3H) and carbon- 14 (i.e.,14C) isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium (i.e.,2H) may afford certain therapeutic advantages resulting from greater metabolic stability (e.g., increased in vivo half-life or reduced dosage requirements) and hence may be preferred in some circumstances. Isotopically labeled compounds of the disclosure can generally be prepared by following procedures analogous to those disclosed in the examples herein by substituting an isotopically labeled reagent for a non- isotopically labeled reagent.

[0068] The term “prodrug” refers to compounds that are transformed in vivo to yield a disclosed compound or a pharmaceutically acceptable salt, hydrate or solvate of the compound.The transformation may occur by various mechanisms (such as by esterase, amidase, phosphatase, oxidative and or reductive metabolism) in various locations (such as in the intestinal lumen or upon transit of the intestine, blood or liver). Prodrugs are well known in the ail (for example, see Rautio, Kumpulainen, et al., Nature Reviews Drug Discovery 2008, 7, 255).Compounds

[0069] In one aspect, the invention relates to a compound of Formula Ior a pharmaceutically acceptable salt thereof, wherein:X1is S, O, NRc;R1is -C1-4alkylC(O)OH, -C1-4alkylC(O)OC1-4alkyl, -OC1-4alkyleneC(O)OC1-4alkyl, -C1-4alkylC(O)NRcRd,R2is, SC1-6alkyl, SC1-4alkylene, SC1-4alkylR13, SC1-4alkylN(Ra)(Rb), or =S;R13is selected from the group consisting of hydrogen, halogen, OH, C(O)OH, - C(O)NRcRd, C(O)OC1-4alkyl, cyclohexyl, morpholinyl, phenyl, indole, pyrrolidine, pyridyl ;R3is absent or hydrogen;Raand Rbare independently selected from the group consisting of hydrogen, CN, C1-4alkyl and C2-4alkenyl; each of R4, R5, R6, and R7is independently selected from the group consisting of hydrogen, halogen, NO2, CN, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, OC1-4alkylene-R14, guanidinyl and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, NRcRd, C1-4alkyl, C(O)OH, C(O)OC1-4alkyl, OC1-4alkyl, C(O)NRcRd, OC(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo;R8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C1-4alkyl, C1-4haloalkyl, NHC(O)C1-4alkyl, OC1-4alkyl, C(O)OH,C(O)OC1-4alkyl, C(O)NRcRd, S(O)qNRcRd, NHC(O)NRcRd, guanidinyl, NHCN(C(O)O- tertbutyl)N(H)C(O)O-tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;R18is hydrogen, C1-4alkyl, C(O)OC1-4alkyl or S(O)qNRcRd;Rcand Rdare independently selected for each occurrence from the group consisting of hydrogen, C1-4alkyl, C1-4haloalkyl C3-6monocycloalkyl, and C(O)OC1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

[0070] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein

[0071] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, S(O)qC1-4alkyl, OC1-4alkyl-R14, and R16.

[0072] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein two of R4, R5, R6, and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaccuticall acceptable salt thereof, wherein R4and R7are hydrogen.

[0073] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein three of R4, R5, R6, and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula 1, or a pharmaceuticall acceptable salt thereof, wherein R4, R5, and R7are hydrogen. In some embodiments, the disclosure relates toa compound of Formula I, or a pharmaceutical! acceptable salt thereof, wherein R4, R6, and R7are hydrogen.

[0074] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are halo. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are Br.

[0075] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are OC1-4alkyl-R14. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are C1-C6-OCH3.

[0076] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein R3is H. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein R3is absent.

[0077] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein R1is

[0078] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein three of R8, R9, R10, R11and R12are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R9, R10, and R11are hydrogen. In some embodiments, the disclosure relates to a compound of Formula 1, or a pharmaceuticall acceptable salt thereof, wherein R8, R10, and R11are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R9, R10, and R11are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R8, R9, and R12are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R8, R9,and R10are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutic all acceptable salt thereof, wherein R8, R9, and R11are hydrogen.

[0079] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein four of R8, R9, R10, R11and R12are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R8, R9, R10, and R11are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R9, R10, R11, and R12are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R8, R9, R11, and R12are hydrogen. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceuticall acceptable salt thereof, wherein R8, R9, R10, and R12are hydrogen.

[0080] In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein one of R8, R9, R10, R11and R12are halo. In some embodiments, the disclosure relates to a compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein one of R8, R9, R10, R11and R12are Cl.

[0081] In another aspect, the disclosure relates to a compound of Formula IIor a pharmaceutically acceptable salt thereof, wherein:X1is S, O, NRc;R1is -C1-4alkylC(O)OH, -C1-4alkylC(O)OC1-4alkyl, -OC1-4alkyleneC(O)OC1-4alkyl, -C1-4alkylC(O)NRcRd,R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, CN, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, OC1-4alkylene-R14, guanidinyl and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, NRcRd, C1-4alkyl, C(O)OH, C(O)OC1-4alkyl, OC1-4alkyl, C(O)NRcRd, OC(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo;R8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C1-4alkyl, C1-4haloalkyl, NHC(O)C1-4alkyl, OC1-4alkyl, C(O)OH, C(O)OC1-4alkyl, C(O)NRcRd, S(O)qNRcRd, NHC(O)NRcRd, guanidinyl, NHCN(C(O)O- tertbutyl)N(H)C(O)O-tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;R18is hydrogen, C1-4alkyl, C(O)OC1-4alkyl or S(O)qNRcRd;Rcand Rdare independently selected for each occurrence from the group consisting of hydrogen, C1-4alkyl, C1-4haloalkyl C3-6monocycloalkyl, and C(O)OC1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

[0082] In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein

[0083] In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, and R16.

[0084] In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein two of R4, R5, R6, and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R4and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R4and R5are hydrogen. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R6and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceu tic ally acceptable salt thereof, wherein R4and R6are hydrogen.

[0085] In some embodiments, the disclosure relates to a compound of Formula 11, or a pharmaceutically acceptable salt thereof, wherein three of R4, R5, R6, and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R4, R6, and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R4, R5, and R7are hydrogen. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R4, R5, and R6are hydrogen. In someembodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein R5, R6, and R7are hydrogen.

[0086] In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are halo. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are Br. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are Cl.

[0087] In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are OC1-4alkyl-R14. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are -OCH3.

[0088] In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7arc C1-4haloalkyl. In some embodiments, the disclosure relates to a compound of Formula II, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are -CF3.

[0089] In another aspect, the disclosure relates to a compound of Formula IIIor a pharmaceutically acceptable salt thereof, whereinR8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NRcRd, C1-4haloalkyl, C(O)NRcRd, S(O)qNRcRd, NHCN(C(O)O-tertbutyl)N(H)C(O)O- tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;Rcand Rdare independently selected for each occurrence from the group consisting of hydrogen and C1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2

[0090] Exemplary compounds of the disclosure and used in the methods and pharmaceutical compositions of the disclosure include but are not limited to the compounds listed in Table 1. Pharmaceutically acceptable salts of the compounds listed in Table 1 are also useful in the compositions and methods of the disclosure.Table 1: Compounds of the Disclosure with Structure and Number.Pharmaceutical Compositions and Kits

[0091] In another aspect, the disclosure provides pharmaceutical compositions comprising a compound of Formulae I, II, III, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In particular, the present disclosure provides pharmaceutical compositions comprising compounds as disclosed herein formulated together with one or more pharmaceutically acceptable carriers. These formulations include those suitable for oral, rectal, topical, buccal, parenteral (e.g., subcutaneous, intramuscular, intradermal, or intravenous), rectal, vaginal, or aerosol administration, although the most suitable form of administration in any given case will depend on the degree and severity of the condition being treated and on the nature of the particular compound being used. For example, disclosed compositions may be formulated as a unit dose, and / or may be formulated for oral or subcutaneous administration.

[0092] In another aspect, the disclosure provides a pharmaceutical composition comprises a compound according to any combination of the Examples described herein, or a pharmaceu tic ally acceptable salt and / or stereoisomer thereof.

[0093] Exemplary pharmaceutical compositions of this disclosure may be used in the form of a pharmaceutical preparation, for example, in solid, semisolid or liquid form, which contains oneor more compounds of the disclosure, as an active ingredient, in admixture with an organic or inorganic carrier or excipient suitable for external, enteral or parenteral applications. The active ingredient may be compounded, for example, with the usual non-toxic, pharmaceutically acceptable carriers for tablets, pellets, capsules, suppositories, solutions, emulsions, suspensions, and any other form suitable for use. The active object compound is included in the pharmaceutical composition in an amount sufficient to produce the desired effect upon the process or condition of the disease.

[0094] For preparing solid compositions such as tablets, the principal active ingredient may be mixed with a pharmaceutical carrier, e.g., conventional tableting ingredients such as corn starch, lactose, sucrose, sorbitol, talc, stearic acid, magnesium stearate, dicalcium phosphate or gums, and other pharmaceutical diluents, e.g., water, to form a solid preformulation composition containing a homogeneous mixture of a compound of the disclosure, or a non-toxic pharmaceutically acceptable salt thereof. When referring to these preformulation compositions as homogeneous, it is meant that the active ingredient is dispersed evenly throughout the composition so that the composition may be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules.

[0095] In solid dosage forms for oral administration (capsules, tablets, pills, dragees, powders, granules and the like), the subject composition is mixed with one or more pharmaceutically acceptable carriers, such as sodium citrate or dicalcium phosphate, and / or any of the following: (1) fillers or extenders, such as starches, lactose, sucrose, glucose, mannitol, and / or silicic acid; (2) binders, such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and / or acacia; (3) humectants, such as glycerol; (4) disintegrating agents, such as agar- agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; (5) solution retarding agents, such as paraffin; (6) absorption accelerators, such as quaternary ammonium compounds; (7) wetting agents, such as, for example, acetyl alcohol and glycerol monostearate; (8) absorbents, such as kaolin and bentonite clay; (9) lubricants, such a talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof; and (10) coloring agents. In the case of capsules, tablets and pills, the compositions may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugars, as well as high molecular weight polyethylene glycols and the like.

[0096] A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may be prepared using binder (for example, gelatin or hydroxypropylmethyl cellulose), lubricant, inert diluent, preservative, disintegrant (for example, sodium starch glycolate or cross-linked sodium carboxymethyl cellulose), surface-active or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the subject composition moistened with an inert liquid diluent. Tablets, and other solid dosage forms, such as dragees, capsules, pills and granules, may optionally be scored or prepared with coatings and shells, such as enteric coatings and other coatings well known in the pharmaceuticalformulating ait.

[0097] Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the subject composition, the liquid dosage forms may contain inert diluents commonly used in the art, such as, for example, water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3- butylene glycol, oils (in particular’, cottonseed, groundnut, corn, germ, olive, castor and sesame oils), glycerol, tetrahydrofuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, cyclodextrins and mixtures thereof.

[0098] Suspensions, in addition to the subject composition, may contain suspending agents as, for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, and mixtures thereof.

[0099] Formulations for rectal or vaginal administration may be presented as a suppository, which may be prepared by mixing a subject composition with one or more suitable non-irritating excipients or carriers comprising, for example, cocoa butter, polyethylene glycol, a suppository wax or a salicylate, and which is solid at room temperature, but liquid at body temperature and, therefore, will melt in the body cavity and release the active agent.

[0100] Dosage forms for transdermal administration of a subject composition include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. Theactive component may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants which may be required.

[0101] The ointments, pastes, creams and gels may contain, in addition to a subject composition, excipients, such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide, or mixtures thereof.

[0102] Powders and sprays may contain, in addition to a subject composition, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays may additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

[0103] Compositions and compounds of the present disclosure may alternatively be administered by aerosol. This is accomplished by preparing an aqueous aerosol, liposomal preparation or solid particles containing the compound. A non-aqueous (e.g., fluorocarbon propellant) suspension could be used. Sonic nebulizers may be used because they minimize exposing the agent to shear, which may result in degradation of the compounds contained in the subject compositions. Ordinarily, an aqueous aerosol is made by formulating an aqueous solution or suspension of a subject composition together with conventional pharmaceutically acceptable carriers and stabilizers. The carriers and stabilizers vary with the requirements of the particular subject composition, but typically include non-ionic surfactants (Tweens, Pluronics, or polyethylene glycol), innocuous proteins like serum albumin, sorbitan esters, oleic acid, lecithin, amino acids such as glycine, buffers, salts, sugars or sugar alcohols. Aerosols generally are prepared from isotonic solutions.

[0104] Pharmaceutical compositions of this disclosure suitable for parenteral administration comprise a subject composition in combination with one or more pharmaceutically-acceptable sterile isotonic aqueous or non-aqueous solutions, dispersions, suspensions or emulsions, or sterile powders which may be reconstituted into sterile injectable solutions or dispersions just prior to use, which may contain antioxidants, buffers, bacteriostats, solutes which render the formulation isotonic with the blood of the intended recipient or suspending or thickening agents.

[0105] Examples of suitable aqueous and non-aqueous carriers which may be employed in the pharmaceutical compositions of the disclosure include water, ethanol, polyols (such as glycerol, propylene glycol, polyethylene glycol, and the like), and suitable mixtures thereof, vegetable oils,such as olive oil, and injectable organic esters, such as ethyl oleate and cyclodextrins. Proper fluidity may be maintained, for example, by the use of coating materials, such as lecithin, by the maintenance of the required particle size in the case of dispersions, and by the use of surfactants.

[0106] In another aspect, the disclosure provides enteral pharmaceutical formulations including a disclosed compound and an enteric material; and a pharmaceutically acceptable carrier or excipient thereof. Enteric materials refer to polymers that are substantially insoluble in the acidic environment of the stomach, and that are predominantly soluble in intestinal fluids at specific pHs. The small intestine is the part of the gastrointestinal tract (gut) between the stomach and the large intestine, and includes the duodenum, jejunum, and ileum. The pH of the duodenum is about 5.5, the pH of the jejunum is about 6.5 and the pH of the distal ileum is about 7.5. Accordingly, enteric materials are not soluble, for example, until a pH of about 5.0, of about 5.2, of about 5.4, of about 5.6, of about 5.8, of about 6.0, of about 6.2, of about 6.4, of about 6.6, of about 6.8, of about 7.0, of about 7.2, of about 7.4, of about 7.6, of about 7.8, of about 8.0, of about 8.2, of about 8.4, of about 8.6, of about 8.8, of about 9.0, of about 9.2, of about 9.4, of about 9.6, of about 9.8, or of about 10.0. Exemplary enteric materials include cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP), polyvinyl acetate phthalate (PVAP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), cellulose acetate trimellitate, hydroxypropyl methylcellulose succinate, cellulose acetate succinate, cellulose acetate hexahydrophthalate, cellulose propionate phthalate, cellulose acetate maleate, cellulose acetate butyrate, cellulose acetate propionate, copolymer of methylmethacrylic acid and methyl methacrylate, copolymer of methyl acrylate, methylmethacrylate and methacrylic acid, copolymer of methylvinyl ether and maleic anhydride (Gantrez ES series), ethyl methyacrylate-methylmethacrylate- chlorotrimethylammonium ethyl acrylate copolymer, natural resins such as zein, shellac and copal collophorium, and several commercially available enteric dispersion systems (e. g. , Eudragit L3OD55, Eudragit FS30D, Eudragit L100, Eudragit S100, Kollicoat EMM30D, Estacryl 30D, Coateric, and Aquateric). The solubility of each of the above materials is either known or is readily determinable in vitro. The foregoing is a list of possible materials, but one of skill in the art with the benefit of the disclosure would recognize that it is not comprehensive and that there are other enteric materials that would meet the objectives of the present disclosure.

[0107] Advantageously, the disclosure also provides kits for use by e.g., a consumer in need of HBV infection treatment. Such kits include a suitable dosage form such as those describedabove and instructions describing the method of using such dosage form tomediate, reduce or prevent HBV infection. The instructions would direct the consumer or medical personnel to administer the dosage form according to administration modes known to those skilled in the art. Such kits could advantageously be packaged and sold in single or multiple kit units. An example of such a kit is a so-called blister pack. Blister packs are well known in the packaging industry and are being widely used for the packaging of pharmaceutical unit dosage forms (tablets, capsules, and the like). Blister packs generally consist of a sheet of relatively stiff material covered with a foil of a preferably transparent plastic material. During the packaging process recesses are formed in the plastic foil. The recesses have the size and shape of the tablets or capsules to be packed. Next, the tablets or capsules are placed in the recesses and the sheet of relatively stiff material is sealed against the plastic foil at the face of the foil which is opposite from the direction in which the recesses were formed. As a result, the tablets or capsules are sealed in the recesses between the plastic foil and the sheet. Preferably the strength of the sheet is such that the tablets or capsules can be removed from the blister pack by manually applying pressure on the recesses whereby an opening is formed in the sheet at the place of the recess. The tablet or capsule can then be removed via said opening.

[0108] It may be desirable to provide a memory aid on the kit, e.g., in the form of numbers next to the tablets or capsules whereby the numbers correspond with the days of the regimen which the tablets or capsules so specified should be ingested. Another example of such a memory aid is a calendar printed on the card, e.g., as follows “First Week, Monday, Tuesday, . . . etc. . . . Second Week, Monday, Tuesday, . . .” etc. Other variations of memory aids will be readily apparent. A “daily dose” can be a single tablet or capsule or several pills or capsules to be taken on a given day. Also, a daily dose of a first compound can consist of one tablet or capsule while a daily dose of the second compound can consist of several tablets or capsules and vice versa. The memory aid should reflect this.Methods

[0109] In a further aspect, a method for treating a hepatitis B infection in a patient in need thereof is provided, comprising administering to a subject or patient an effective amount of a disclosed compound, and / or administering a first disclosed compound and optionally, an additional, different disclosed compound(s). In another embodiment, a method for treating ahepatitis B infection in a patient in need thereof is provided, comprising administering to a subject or patient a therapeutically effective amount of a disclosed pharmaceutical composition or a pharmaceutical composition comprising a disclosed compound, or two or more disclosed compounds, and a pharmaceutically acceptable excipient.

[0110] For use in accordance with this aspect, the appropriate dosage is expected to vary depending on, for example, the particular compound employed, the mode of administration, and the nature and severity of the infection to be treated as well as the specific infection to be treated and is within the purview of the treating physician. Usually, an indicated administration dose may be in the range between about 0.1 to about 1000 μg / kg body weight. In some cases, the administration dose of the compound may be less than 400 μg / kg body weight. In other cases, the administration dose may be less than 200 μg / kg body weight. In yet other cases, the administration dose may be in the range between about 0.1 to about 100 μg / kg body weight. The dose may be conveniently administered once daily, or in divided doses up to, for example, four times a day or in sustained release form.

[0111] A compound of the present disclosure may be administered by any conventional route, in particular: enterally, topically, orally, nasally, e.g., in the form of tablets or capsules, via suppositories, or parenterally, e.g., in the form of injectable solutions or suspensions, for intravenous, intra-muscular, sub-cutaneous, or intra-peritoneal injection. Suitable formulations and pharmaceutical compositions will include those formulated in a conventional manner using one or more physiologically acceptable carriers or excipients, and any of those known and commercially available and currently employed in the clinical setting. Thus, the compounds may be formulated for oral, buccal, topical, parenteral, rectal or transdermal administration or in a form suitable for administration by inhalation or insufflation (either orally or nasally).

[0112] For oral administration, pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g. lactose, microcrystalline cellulose or calcium hydrogen phosphate); lubricants (e.g., magnesium stearate, talc or silica); disintegrants (e.g., potato starch or sodium starch glycollate); or wetting agents (e.g., sodium lauryl sulphate). Tablets may be coated by methods well known in the art. Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dryproduct for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g., methyl or propyl-p- hydroxybenzoates or sorbic acid). Preparations may also contain buffer salts, flavoring, coloring and sweetening agents as appropriate.

[0113] Preparations for oral administration may also be suitably formulated to give controlled- release or sustained release of the active compound(s) over an extended period. For buccal administration the compositions may take the form of tablets or lozenges formulated in a conventional manner known to the skilled artisan.

[0114] A disclosed compound may also be formulated for parenteral administration by injection e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain additives such as suspending, stabilizing and / or dispersing agents. Alternatively, the compound may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. Compounds may also be formulated for rectal administration as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides.

[0115] Also contemplated herein are methods and compositions that include a second active agent or administering a second active agent. For example, in addition to being infected with HBV, a subject or patient can further have HBV infection-related co-morbidities, i.e., diseases and other adverse health conditions associated with, exacerbated by, or precipitated by being infected with HBV. Contemplated herein are disclosed compounds in combination with at least one other agent that has previously been shown to treat these HBV-infection-related conditions.

[0116] In some cases, a disclosed compound may be administered as part of a combination therapy in conjunction with one or more antivirals. Example antivirals include nucleoside analogs, interferon a, and other assembly effectors, for instance heteroaryldihydropyrimidines (HAPs) such as methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)- 1 ,4-dihydropyrimidine-5- carboxylate (HAP-1). For example, provided herein is a method of treating a patient suffering fromhepatitis B infection comprising administering to the patient a first amount of a disclosed compound and a second amount of an antiviral, or other anti HBV agent, for example a second amount of a second compound selected from the group consisting of: an HBV capsid assembly promoter (for example, GLS4, BAY 41-4109, AT- 130, DVR-23 (e.g., as depicted below),NVR 3-778, NVR1221 (by code); and N890 (as depicted below):other capsid inhibitors such as those disclosed in the following patent applications hereby incorporated by reference: W02014037480, WO2014184328, W02013006394, WO2014089296, W02014106019, WO2013102655, WO2014184350, WO2014184365, WO2014161888, WO2014131847, WO2014033176, WO2014033167, and W02014033170; Nucleos(t)ide analogs interfering with viral polymerase, such as entecavir (Baraclude), Lamivudine, (Epivir-HBV), Telbivudine (Tyzeka, Sebivo), Adefovir dipivoxil (Hepsera), Tenofovir (Viread), Tenofovir alafenamide fumarate (TAF), prodrugs of tenofavir (e.g. AGX-1009), L-FMAU (Clevudine), LB8O38O (Besifovir) and:viral entry inhibitors such as Myrcludcx B and related lipopeptide derivatives; HBsAg secretion inhibitors such as REP 9AC’ and related nucleic acidbased amphipathic polymers, HBF-0529 (PBHBV-001), PBHBV-2-15 as depicted below:and BM601 as depicted below:disruptors of nucleocapsid formation or integrity such as NZ-4 / W28F:; cccDNA formation inhibitors such as BSBI-25,CCC-0346, CCC-0975 (as depicted below):

[0117] HBc directed transbodies such as those described in Wang Y, et al, Transbody against hepatitis B virus core protein inhibits hepatitis B virus replication in vitro, Int. Immunopharmacol (2014), located at / / dx.doi.org / 10.1016 / j.intimp.2015.01.028; antiviral core protein mutant (such as Cpl83-V124W and related mutations as described in WO / 2013 / 010069, WO2014 / 074906, each incorporated by reference); inhibitors of HBx-interactions such as RNAi, antisense and nucleic acid based polymers targeting HBV RNA;, e.g., RNAi (for example ALN-HBV, ARC-520, TKM- HBV, ddRNAi), antisense (ISIS-HBV), or nucleic acid based polymer: (REP 2139-Ca); immunostimulants such as Interferon alpha 2a (Roferon), Intron A (interferon alpha 2b), Pegasys (peginterferon alpha 2a), Pegylated IFN 2b, IFN lambda la and PEG IFN lambda la, Wellferon,Roferon, Infergen, lymphotoxin beta agonists such as CBE11 and BS1); Non-Interferon Immune enhancers such as Thymosin alpha-1 (Zadaxin) and Interleukin-7 (CYT107); TLR-7 / 9 agonists such as GS-9620, CYT003, Resiquimod; Cyclophilin inhibitors such as NVP018; OCB-030; SCY- 635; Alisporivir; NIM811 and related cyclosporine analogs; vaccines such as GS-4774, TG1050, Core antigen vaccine; SMAC mimetics such as birinapant and other lAP-antagonists; Epigenetic modulators such as KMT inhibitors (EZH1 / 2, G9a, SETD7, Suv39 inhibitors), PRMT inhibitors, HDAC inhibitors, SIRT agonists, HAT inhibitors, WD antagonists (e.g. OICR-9429), PARP inhibitors, APE inhibitors, DNMT inhibitors, LSD1 inhibitors, JMJD HDM inhibitors, and Bromodomain antagonists; kinase inhibitors such as TKB1 antagonists, PLK1 inhibitors, SRPK inhibitors, CDK2 inhibitors, ATM & ATR kinase inhibitors; STING Agonists; Ribavirin; N-acetyl cysteine ; NOV-205 (BAM205); Nitazoxanide (Alinia), Tizoxanide; SB 9200 Small Molecule Nucleic Acid Hybrid (SMNH); DV-601; Arbidol; FXR agonists (such as GW 4064 and Fexaramin); antibodies, therapeutic proteins, gene therapy, and biologies directed against viral components or interacting host proteins.

[0118] In some embodiments, the disclosure provides a method of treating a hepatitis B infection in a patient in need thereof, comprising administering a first compound selected from any one of the disclosed compounds, and one or more other HBV agents each selected from the group consisting of HBV capsid assembly promoters, HBF viral polymerase interfering nucleosides, viral entry inhibitors, HBsAg secretion inhibitors, disruptors of nucleocapsid formation, cccDNA formation inhibitors, antiviral core protein mutant, HBc directed transbodies, RNAi targeting HBV RNA, immuno stimulants, TLR-7 / 9 agonists, cyclophilin inhibitors, HBV vaccines, SMAC mimetics, epigenetic modulators, kinase inhibitors, and STING agonists. In some embodiments, the disclosure provides a method of treating a hepatitis B infection in a patient in need thereof, comprising administering an amount of a disclosed compound, and administering another HBV capsid assembly promoter.

[0119] In some embodiments, the first and second amounts together comprise a pharmaceutically effective amount. The first amount, the second amount, or both may be the same, more, or less than effective amounts of each compound administered as monotherapies. Therapeutically effective amounts of a disclosed compound and antiviral may be co-administered to the subject, i.e., administered to the subject simultaneously or separately, in any given order and by the same or different routes of administration. In some instances, it may be advantageous toinitiate administration of a disclosed compound first, for example one or more days or weeks prior to initiation of administration of the antiviral. Moreover, additional drugs may be given in conjunction with the above combination therapy.

[0120] In another embodiment, a disclosed compound may be conjugated (e.g., covalently bound directly or through molecular linker to a free carbon, nitrogen (e.g., an amino group), or oxygen (e.g., an active ester) of a disclosed compound), with a detection moiety, for e.g., a fluorophore moiety (such a moiety may for example re-emit a certain light frequency upon binding to a virus and / or upon photon excitation). Contemplated fluorophores include AlexaFluor® 488 (Invitrogen) and BODIPY FL (Invitrogen), as well as fluorescein, rhodamine, cyanine, indocarbocyanine, anthraquinones, fluorescent proteins, aminocoumarin, methoxycoumarin, hydroxycoumarin, Cy2, Cy3, and the like. Such disclosed compounds conjugated to a detection moiety may be used in e.g., a method for detecting HB V or biological pathways of HB V infection, e.g., in vitro or in vivo', and / or methods of assessing new compounds for biological activity.EXAMPLES

[0121] The compounds described herein can be prepared in a number of ways based on the teachings contained herein and synthetic procedures known in the art. In the description of the synthetic methods described below, it is to be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and workup procedures, can be chosen to be the conditions standard for that reaction, unless otherwise indicated. It is understood by one skilled in the ail of organic synthesis that the functionality present on various portions of the molecule should be compatible with the reagents and reactions proposed. Substituents not compatible with the reaction conditions will be apparent to one skilled in the ail, and alternate methods are therefore indicated. The starting materials for the examples are either commercially available or are readily prepared by standard methods from known materials.

[0122] At least some of the compounds identified as “intermediates” herein are contemplated as compounds of the disclosure.

[0123] The compounds of the invention may be prepared readily using the following methods.

[0124] Abbreviations:AcOH Acetic acidACN AcetonitrileBoc2O Di-tert-butyl dicarbonate nBuLi n-ButyllithiumDCM DichloromethaneDIAD Diisopropyl azodicarboxylateDIEA Diisopropyl ethylamineDMAP 4-DimethylaminopyridineDMF N,N-DimethylformamideDMSO Dimethyl sulfoxideDPPF 1,1’ -Bis(diphenylphosphino)ferroceneEA, EtOAc Ethyl acetateEt3N TriethylamineHATU Hexafluorophosphate Azabenzotriazole Tetramethyl Uronium h, hr Hour(s)HPLC High performance liquid chromatographyLCMS Liquid chromatography-mass spectrometryMeOH MethanolNMO N-Methylmorpholine-N-OxideNBS N-BromosuccinimidePE Petroleum ether iPrOH Isopropanol rt, r.t. Room temperatureSFC Supercritical Fluid ChromatographyTEA TriethylamineTFA Trifluoroacetic acidTHF TetrahydrofuranTLC Thin-layer chromatographyXPhos 2-Dicyclohexylphosphino-2’ ,4’ ,6’ -triisopropylbiphenylExample 1: Synthesis of Compounds of the DisclosureExperimental details for Compound 1Step 1: Synthesis of 3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one

[0125] 3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one was obtained commercially from Enamine. Off white solid.

[0126] 1H NMR (400 MHz, DMSO-d6) δ 13.03 (s, 1H), 7.95 (dd, J= 1.3, 7.9 Hz, 1H), 7.18 - 7.76 (m, 1H), 7.52 - 7.32 (m, 5H), 7.30 - 7.25 (m, 2H); LC-MS: 96.68% at 2.653 min; m / z 253.0 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 urn), Mobile Phase-A: 2.5 mM Aq NH4OAC, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 98.54% at 8.74 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 2: Synthesis of 2-(allyl thio)-3-phenylquinazolin-4(3H)-one (Compound 1)

[0127] To a solution of 3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (100 mg, 0.39 mmol) in DMF (8 mL) was added K2CO3(109 mg, 0.79 mmol) and allyl bromide (52 mg, 0.43 mmol) slowly at 0 °C and the reaction mixture was stirred at room temperature for 2 h. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ice cold water (30 mL). The obtained solid was filtered and residue was washed with hexane and dried to afford 2-(allyl thio)-3-phenylquinazolin-4(3H)-one (60 mg, 0.20 mmol) as white solid. Yield- 51%

[0128] 1H NMR (400 MHz, DMSO-d6) δ 8.08 (dd, J = 1.0, 7.9 Hz, 1H), 7.88 - 7.79 (m, 1H), 7.63 (d, J= 8.1 Hz, 1H), 7.60 - 7.52 (m, 3H), 7.51 - 7.41 (m, 3H), 5.96 - 5.86 (m, 1H), 5.33 (dd, J = 1.3, 17.0 Hz, 1H), 5.12 (dd, J = 0.8, 10.0 Hz, 1H), 3.83 (d, 7= 7.0 Hz, 2H); ); LC-MS: 99.65% at 3.435 min; m / z 295.2 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 im), Mobile Phase-A: 0.025% Aq TFA+5% ACN, Mobile Phase-B: ACN+ 5% 0.025% Aq TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 99.42% at 8.65 min.Experimental details for Compound 2Step 1: Synthesis of 2-amino-N-phenylnicotinamide

[0129] To a solution of 2- aminonicotinic acid (200 mg, 1.44) in DMF (15 mL) was added Aniline (161 mg, 1.73 mmol) EDC.HCl (412 mg, 2.16 mmol) and DMAP (351 mg, 2.88 mmol) at 0 °C and the reaction mixture was stirred at room temperature for 16h. Progress of reaction was monitored by TLC. After completion, the reaction mixture was diluted with cold H2O (60 mL) and extracted with EtOAc (3 x 50 mL). The organic layer was separated, and washed with ice cold water (2 x 40 mL) dried over anhydrous Na2SO4and concentrated in vacuo. The crude obtained was diluted with DCM, the solid obtained was collected by filtration and dried to afford 2-amino- N-phenylnicotinamide (230 mg, 1.07 mmol) as pale yellow solid.

[0130] 1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 8.13 (dd, J = 1.8, 4.8 Hz, 1H), 8.03 (dd, J = 1.7, 7.7 Hz, 1H), 7.69 (dd, J = 1.0, 8.6 Hz, 2H), 7.39 - 7.29 (m, 2H), 7.14 - 7.06 (m, 1H), 6.95 (s, 2H), 6.66 (dd, J = 4.8, 7.7 Hz, 1H); LC-MS: m / z 214.1 [M+H]+Step 2: Synthesis of 3-Phenyl-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(lH)-one

[0131] To a solution of 2-amino-N-phenylnicotinamide (50 mg, 0.23 mmol) in DCM (10 mL) was added Thiocarbonyldiimidazole (62.6 mg, 0.35 mmol) DMAP (3 mg, 0.02 mmol) at RT and the reaction mixture was stirred at 40 °C for 16 h. Progress of reaction was monitored by TLC. After completion, the reaction mixture was diluted with DCM (50 mL) and washed with water (3 x 50 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude obtained was diluted with ethanol, the solid obtained was collected by filtration and residue was washed with DCM (20 mL) and dried to afford 3-phenyl-2-thioxo-2,3- dihydropyrido[2,3-d]pyrimidin-4(lH)-one (10 mg. 0.03 mmol) as off white solid. Yield- 14%.

[0132] 1H NMR (500 MHz, DMSO-d6) δ 13.46 (br s, 1H), 8.73 (dd, J= 1.5, 4.5 Hz, 1H), 8.31 (dd, J = 1.3, 7.9 Hz, 1H), 7.50 - 7.43 (m, 2H), 7.42 - 7.34 (m, 2H), 7.26 (d, J = 7.4 Hz, 2H); LC- MS: 96.40% at 2.036 min; m / z 256.1 [M+H]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 98.28% at 5.725 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5μ),Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 3: Synthesis of 2-(Allylthio)-3-phenylpyrido[2,3-d]pyrimidin-4(3H)-one (Compound 2)

[0133] To a solution of 3-Phenyl-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(lH)-one (100 mg, 0.39 mmol) in DMF (8 mL) was added K2CO3(108 mg, 0.78 mmol) and allyl bromide slowly at 0°C and the reaction mixture was stirred at room temperature for 6h. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ice cold water (50 mL). The obtained solid was filtered and residue was washed with hexane and dried to afford 2-(allylthio)-3-phenylpyrido[2,3-d]pyrimidin-4(3H)-one (Compound 2) as a pale brown solid. Yield: 35%.

[0134] 1H NMR (400 MHz, DMSO-d6) δ 8.93 (dd, J= 2.0, 4.6 Hz, 1H), 8.47 (dd, J= 2.1, 7.8 Hz, 1H), 7.63 - 7.54 (m, 3H), 7.53 - 7.45 (m, 3H), 5.99 - 5.88 (m, 1H), 5.33 (dd, J = 1.6, 17.0 Hz, 1H), 5.13 (dt, J = 0.8, 10.0 Hz, 1H), 3.86 (d, J = 7.0 Hz, 2H); LC-MS: 97.51% at 2.433 min; m / z 296.0 [M+H]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phasc-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 97.78% at 8.87 min [Column: XSELECT CSH C18 150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Experimental details for Compounds 3 and 4:Step-1: Synthesis of 3-phenyl-2-thioxo-2,3-dihydropyrido[3,4-d]pyrimidin-4(lH)-one (Compound 3)

[0135] To a solution of 3-aminoisonicotinic acid (500 mg, 3.62 mmol) in CH3CN (10 mL) was added isothiocyanatobenzene (488 mg, 3.62 mmol) and EtsN (0.26 mL, 3.62 mmol) at RT and the reaction mixture was stirred at 150 °C in microwave for 0.5 h. Progress of reaction was monitored by TLC. After completion, reaction mixture was cooled to RT and solvent was evaporated. Residuewas triturated with CH2CI2, white solid was obtained, filtered the solid and washed with CH2CI2and dried under vacuum to afford 2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(lH)-one (Compound 3) (190 mg, 1.06 mmol) as pale yellow solid. Yield- 21%

[0136] 1H NMR (500 MHz, DMSO-d6) δ 13.26 (br s, 1H), 8.82 (s, 1H), 8.52 (d, J= 5.1 Hz, 1H), 7.81 (d, J= 5.1 Hz, 1H), 7.52 - 7.46 (m, 2H), 7.45 - 7.38 (m, 1H), 7.29 (d, J = 7.7 Hz, 2H); LC-MS: 97.90% at 1.960 min; m / z 256.1 [M+H]+[Column: Kinetex EVO C-18 (50x30 mm, 2.6μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 98.50% at 7.50 min [Column: XSELECT CSH Cl 8 150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step-2: Synthesis of 2-(allylthio)-3-phenylpyrido[3,4-d]pyrimidin-4(3H)-one (Compound 4)

[0137] Compound 4 was prepared from Compound 3 according to general procedure as pale yellow Yield- 120 mg, 0.41 mmol, 54.5%

[0138] 1H NMR (400 MHz, DMSO-d6) δ 9.02 (d, J= 0.6 Hz, 1H), 8.62 (d, J= 5.1 Hz, 1H), 7.92 (dd, J = 0.9, 5.1 Hz, 1H), 7.63 - 7.54 (m, 3H), 7.51 - 7.42 (m, 2H), 5.97 - 5.87 (m, 1H), 5.35 (dd, J = 1.6, 17.0 Hz, 1H), 5.14 (dt, J = 0.8, 10.0 Hz, 1H), 3.86 (d, J = 7.1 Hz, 2H); LC-MS: 99.05% at 2.941 min; m / z 296.1 [M+H]+[Column: XSelect CSH C-18 (3.0x50 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.81% at 10.51 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 5Step-1: Synthesis of 3-phenyl-2-thioxo-2,3-dihydropyrido[3,4-d]pyrimidin-4(lH)-one

[0139] To a solution of 3-aminopicolinic acid (200 mg, 1.45 mmol) in DMF(8 mL) was added Phenylisothiocyanate (215 mg, 1.59 mmol) at room temperature and the resulting reaction mixturewas stirred at 80°C for 16 h. Progress of the reaction was monitored by TLC. After completion of reaction, Reaction mixture was diluted with cold water (50 mL) and extracted with EtOAC (2x 70 mL). Combined organic layer was washed with cold water (2x 30 mL) and dried over Na2SO4and concentrated in vacuo. Residue was diluted with ethanol (40 mL), formed solid was filtered and residue was washed with DCM (30 mL) to afford 3-phenyl-2-thioxo-2,3-dihydropyrido[3,4- d]pyrimidin-4(lH)-one (130 mg, 0.51 mmol) as off white solid. Yield- 35 %.

[0140] 1H NMR (500 MHz, DMSO-d6) δ 13.06 (br s, 1H), 8.60 (dd, J= 1.2, 4.2 Hz, 1H), 7.85 - 7.80 (m, 1H), 7.79 - 7.74 (m, 1H), 7.53 - 7.46 (m, 2H), 7.44 - 7.38 (m, 1H), 7.29 (d, J= 7.4 Hz, 2H); LC-MS: 98.31% at 1.705 min; m / z 256.0 [M+H]+[Column: EVO C-18 (3.0x50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.48% at 6.36 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase- A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Step-2: Synthesis of 2-(allylthio)-3-phenylpyrido[3,2-d]pyrimidin-4(3H)-one (Compound 5)

[0141] Compound 5 was prepared from 3-phenyl-2-thioxo-2,3-dihydropyrido[3,4- d]pyrimidin-4(lH)-one according to general procedure to afford 2-(allylthio)-3-phenylpyrido[3,2- d]pyrimidin-4(3H)-one (Compound 5) (55 mg, 0.8 mmol) as off white solid. Yield: 47%.

[0142] 1H NMR (400 MHz, DMSO-d6) δ 8.74 (br d, J = 3.2 Hz, 1H), 8.05 (dd, J = 1.5, 8.3 Hz, 1H), 7.82 (dd, J = 4.4, 8.3 Hz, 1H), 7.63 - 7.53 (m, 3H), 7.51 - 7.43 (m, 2H), 5.96 - 5.86 (m, 1H), 5.33 (dd, J = 1.5, 16.9 Hz, 1H), 5.13 (dt, J = 0.7, 10.0 Hz, 1H), 3.84 (d, J = 7.0 Hz, 2H); LC- MS: 99.69% at 2.512 min; m / z 296.0 [M+H]+ [Column: EVO C-18 (3.0x50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: >99.00% at 10.19 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water].Experimental details for Compound_6:Step 1: Synthesis of methyl 3-(3-phenylthioureido) thiophene-2-carboxylate:

[0143] Methyl 3-aminothiophene-2-carboxylate (500 mg, 3.18 mmol) in 1,4-dioxane (15 mL) was added isothiocyanatobenzene (515 mg, 3.81 mmol) at RT and the reaction mixture was stirred at 60 °C for 16 h. Progress of reaction was monitored by TLC. After completion, reaction mixture was cooled to RT. The formed solid was collected by filtration and residue was washed with hexane and dried under vacuum to afford methyl 3-(3-phenylthioureido) thiophene-2-carboxylate (400 mg, 1.37 mmol.43%) as off white solid. Yield-43%.

[0144] 1H NMR (500 MHz, DMSO-d6) δ 10.78 (s, 1H), 10.24 (s, 1H), 8.43 (d, J = 5.4 Hz, 1H), 7.84 (d, J= 5.7 Hz, 1H), 7.49 (br d, J= 7.7 Hz, 2H), 7.41 (t, J= 7.7 Hz, 2H), 7.31 - 7.20 (m, 1H), 3.78 (s, 3H); LC-MS: m / z 292.9 [M+H]+Step 2: Synthesis of 3-phenyl-2-thioxo-2,3-dihydrothieno[3,2-d]pyrimidin-4(lH)-one (Compound 6):

[0145] To a solution of methyl 3-(3-phenylthioureido) thiophene-2-carboxylate (300 mg, 1.03 mmol) in Methanol (15 mL) was added NaOMc (113, 2.05 mmol) at RT and the reaction mixture was stirred at 60 °C for 2 h. Progress of reaction was monitored by TLC. After completion, cooled to RT and the reaction mixture was distilled under vacuum to get crude compound. Crude was diluted with 10% MeoH in DCM (100 mL) and washed with water (2 x 20 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo to afford 3-phenyl-2- thioxo-2,3-dihydrothieno[3,2-d]pyrimidin-4(lH)-one (Compound 6) (120 mg ,0.46 mmol) as off white solid. Yield-44%.

[0146] 1H NMR (500 MHz, DMSO-d6) δ 13.49 (s, 1H), 8.21 (d, J = 5.4 Hz, 1H), 7.50 - 7.44 (m, 2H), 7.43 - 7.37 (m, 1H), 7.26 (d, J = 7.4 Hz, 2H), 7.08 (d, 7= 5.1 Hz, 1H); LC-MS: 99.55% at 2.077 min; m / z 258.9 [M-H]’ [Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase- A: 0.025% Aq Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.53% at 5.96 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compounds 7 and 8:Step 1: Synthesis of ethyl 2-(3-phenylthioureido) thiophene-3-carboxylate:

[0147] Ethyl 2-aminothiophene-3-carboxylate (500 mg, 2.92 mmol) in t-BuOH (15 mL) was added isothiocyanatobenzene (473 mg, 3.50 mmol) and EtsN (0.61 mL, 8.77 mmol) at RT and the reaction mixture was stirred at 80 °C for 16 h. Progress of reaction was monitored by TLC. After completion, reaction mixture was cooled to RT and distilled under vacuum. The residue was diluted with DCM (30 mL) and washed with water (3 x 20 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude product was purified by Combi flash chromatography (5% EtOAc in hexanes) to afford methyl 2-(3-phcnylthiourcido) thiophcnc- 3-carboxylate (270 mg, 0.88 mmol, 30.30%) as off white solid.

[0148] 1H NMR (500 MHz, DMSO-d6) δ 11.60 (s, 1H), 11.13 (br s, 1H), 7.50 (br d, J = 7.7 Hz, 2H), 7.42 (t, J = 7.7 Hz, 2H), 7.30 - 7.21 (m, 1H), 7.18 (d, J = 5.9 Hz, 1H), 6.91 (d, J = 5.9 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 1.28 (t, J = 7.0 Hz, 3H); LC-MS: m / z 307.1 [M+H]+Step 2: Synthesis of 3-phenyl-2-thioxo-2,3-dihydrothieno[2,3-d]pyrimidin-4(lH)-one (Compound 7)

[0149] To a solution of ethyl 2-(3-phenylthioureido)thiophene-3-carboxylate (420 mg, 1.37 mmol) in methanol (10 mL) was added NaOMe (150 mg, 2.72 mmol) at RT and the reaction mixture was stirred at 60 °C for 2 h. Progress of reaction was monitored by TLC. After completion, the reaction mixture was distilled off and the residue was diluted with 10% MeoH in DCM (100 mL) and washed with water (2 x 20 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo to afford 3-phenyl-2-thioxo-2,3-dihydrothieno[2,3- d]pyrimidin-4(lH)-one (compound 7) (230 mg, 0.88 mmol) as off white solid. Yeild-65%.

[0150] 1H NMR (500 MHz, DMSO-d6) δ 13.78 (br s, 1H), 7.49 - 7.42 (m, 2H), 7.40 - 7.33 (m, 1H), 7.24 - 7.15 (m, 4H); LC-MS: 99.00% at 2.082 min; m / z 260.9 [M+H]+[Column: LUNA C- 18 (50x3.0 mm, 2.6 μm), Mobile Phase- A: 0.25% Formic acid in water, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.20% at 8.25 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Watcr].Step 3: Synthesis of 2-(allylthio)-3-phenylthieno[2,3-d]pyrimidin-4(3H)-one (Compound 8)

[0151] Compound 8 was prepared from Compound 7 according to general procedure as white solid. Yield- 150 mg, 0.50 mmol, 56.5%.

[0152] 1H NMR (500 MHz, DMSO-d6) δ 7.60 - 7.53 (m, 3H), 7.51 (d, J = 5.7 Hz, 1H), 7.46 - 7.40 (m, 2H), 7.36 (d, J = 5.9 Hz, 1H), 5.92 - 5.84 (m, 1H), 5.34 - 5.25 (m, 1H), 5.12 (d, J = 10.1 Hz, 1H), 3.77 (d, J = 6.8 Hz, 2H); LC-MS: 99.65% at 2.974 min; m / z 301.1 [M+H]+[Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase- A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.89% at 8.24 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compounds 9 and 10:Step 1: Synthesis of 7-bromo-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 9)

[0153] Compound 9 was prepared from corresponding 2-amino-4-bromobenzoic acid and phenyisothiocyanate according to general procedure. Off white solid, Yield- 31 mg, 0.09 mmol, 4%

[0154] 1H NMR (400 MHz, DMSO-d6) δ 13.05 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.62 (d, J = 1.7 Hz, 1H), 7.53 - 7.44 (m, 3H), 7.43 - 7.37 (m, 1H), 7.30 - 7.25 (m, 2H); LC-MS: 94.44% at 2.728 min; m / z 334.2 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase- A: 0.025% Aq. Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 96.91% at 10.74 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 2: Synthesis of 2-(allylthio)-7-bromo-3-phenylquinazolin-4(3H)-one (Compound 10)

[0155] Compound 10 was prepared from Compound 9 according to general procedure. Off white solid, Yield-(22 mg, 0.06 mmol) 28%

[0156] 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 1H), 7.81 (d, 7= 1.7 Hz, 1H), 7.59 - 7.47 (m, 4H), 7.34 - 7.28 (m, 2H), 5.97 - 5.86 (m, 1H), 5.30 (dd, J = 1.3, 16.9 Hz, 1H), 5.15 (d, J = 9.5 Hz, 1H), 3.81 (d, J = 7.1 Hz, 2H); LC-MS: 97.76% at 3.263 min; m / z 374.2 [M+H]+[Column: XBridge BEH C-18(50X3.0 mm, 2.5 im), Mobile Phase-A: 0.025% Aq TFA+5% ACN, Mobile Phase-B: ACN+ 5% 0.025% Aq TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 97.64% at 7.572 min [Column: KINTEX EVO C18 (150 X 4.6 mm, 5 μ), Mobile Phase-A: 0.05% Ammonia in 2.5 mM Ammonium Bicarbonate, Mobile Phase-B: ACN, Flow: 2.0 mL / min, Diluent: ACN: Water],Experimental details for Compounds 11 and 12:Step 1: Synthesis of 5-bromo-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one(Compound 11)

[0157] Compound 11 was prepared from corresponding 2-amino-6-bromobenzoic acid and pheny isothiocyanate according to general procedure using t-butanol and Et3N (2 eq). White solid Yield-60 mg, 0.18 mmol, 21.4%

[0158] 1H NMR (400 MHz, DMSO-d6) δ 13.04 (br s, 1H), 7.63 - 7.55 (m, 2H), 7.52 - 7.35 (m, 4H), 7.27 (br d, J = 7.5 Hz, 2H); LC-MS: 98.74% at 2.574 min; m / z 334.9 [M+2]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 97.72% at 6.96 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 2: Synthesis of 2-(allylthio)-5-bromo-3-phenylquinazolin-4(3H)-one (Compound 12)

[0159] Compound 12 was prepared from Compound 11 according to general procedure. Off white solid, Yield-(45 mg, 0.12 mmol) 33%.

[0160] 1H NMR (400 MHz, DMSO-d6) δ 7.74 - 7.53 (m, 6H), 7.49 - 7.42 (m, 2H), 5.95 - 5.84 (m, 1H), 5.32 (dd, J= 1.3, 16.9 Hz, 1H), 5.12 (d, J = 10.0 Hz, 1H), 3.81 (d, 7= 7.0 Hz, 2H); LC- MS: 98.20% at 3.823 min; m / z 375.2 [M+2]+[Column: XBridge BEH C-18(50X3.0 mm, 2.5 Im), Mobile Phase-A: 0.025% Aq TFA+5% ACN, Mobile Phase-B: ACN+ 5% 0.025% Aq TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 98.14% at 9.46 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 13 and 14:Step 1: Synthesis of 6-fluoro-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 13)

[0161] Compound 13 was prepared from corresponding 2-amino-5-fluorobenzoic acid and phenyisothiocyanate according to general procedure. White solid. Yield-(360 mg, 1.32 mmol), 51%.

[0162] 1H NMR (500 MHz, DMSO-d6) δ 13.12 (s, 1H), 7.75 - 7.63 (m, 2H), 7.52 - 7.45 (m, 3H), 7.43 - 7.37 (m, 1H), 7.27 (d, J = 7.4 Hz, 2H); LC-MS: 99.52% at 2.417 min; m / z 273.1 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Aq. Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.77% at 9.53 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 2: Synthesis of 6-fluoro-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 14)

[0163] Compound 14 was prepared from Compound 13 according to general procedure. White solid, Yield (180 mg, 0.58 mmol) 82%.

[0164] 1H NMR (500 MHz, DMSO-d6) δ 7.78 - 7.67 (m, 3H), 7.59 - 7.51 (m, 3H), 7.47 - 7.41 (m, 2H), 5.93 - 5.85 (m, 1H), 5.31 (d, 7= 17.3 Hz, 1H), 5.11 (d, 7= 10.1 Hz, 1H), 3.80 (d, 7= 6.8Hz, 2H); LC-MS: 98.98% at 3.637 min; m / z 313.0 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 um), Mobile Phase-A: 2.5 mM Aq. NH4OAC, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.67% at 8.93 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA: ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compounds 15 and 16:Step 1: Synthesis of 6-chloro-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 15)

[0165] Compound 15 was prepared from corresponding 2-amino-5-chlorobenzoic acid and phenyisothiocyanate according to general procedure. White solid, Yield-(150 mg, 0.52 mmol) 22%.

[0166] 1H NMR (500 MHz, DMSO-d6) δ 13.15 (s, 1H), 7.88 (d, J = 2.4 Hz, 1H), 7.84 (dd, J = 2.5, 8.8 Hz, 1H), 7.51 - 7.44 (m, 3H), 7.43 - 7.37 (m, 1H), 7.27 (d, J = 7.4 Hz, 2H); LC-MS: 99.85% at 2.623 min; m / z 289.1 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Aq. Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 97.90% at 10.50 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Step 2: Synthesis of 2-(allylthio)-6-chloro-3-phenylquinazolin-4(3H)-one (Compound 16)

[0167] Compound 16 was prepared from Compound 15 according to general procedure. White solid, Yield-(120 mg, 0.36 mmol) 53%

[0168] 1H NMR (500 MHz, DMSO-d6) δ 8.00 (d, J = 2.4 Hz, 1H), 7.85 (dd, J = 2.4, 8.6 Hz, 1H), 7.65 (d, J = 8.6 Hz, 1H), 7.60 - 7.51 (m, 3H), 7.48 - 7.39 (m, 2H), 5.93 - 5.86 (m, 1H), 5.31 (d, J= 17.0 Hz, 1H), 5.11 (d, 7= 9.8 Hz, 1H), 3.81 (d, 7 = 6.8 Hz, 2H); LC-MS: 99.84% at 3.854 min; m / z 329.1 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phasc-A:2.5 mM Aq. NH4OAC, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 98.49% at 9.98 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Experimental details for Compounds 17, 18, 19 & 20:Step 1: Synthesis of methyl 4-oxo-3-phenyl-2-thioxo- 1,2,3, 4-tetrahydroquinazoline-6- carboxylate (Compound 17)

[0169] To a stirred solution of dimethyl 4-aminoisophthalate (1.0 g, 4.780 mmol) in pyridine (10 mL) was added phenylisothiocyanate (711 mg, 5.25 mmol) at RT and the reaction mixture was stirred at 100 °C for 16h. Progress of reaction was monitored by TLC. After completion, the volatiles were removed and was diluted with water (30 mL). The formed solid was collected by filtration and the solids and washed with water and dried under vacuum to afford crude product which was recrystallized from ethanol to afford methyl 4-oxo-3-phenyl-2-thioxo-l, 2,3,4- tetrahydroquinazoline-6-carboxylate (Compound 17) (629 mg, 2.1 mmol) as white solid. Yield: 42%

[0170] 1H NMR (400 MHz, DMSO-d6) δ 13.28 (br s, 1H), 8.46 (d, J= 1.8 Hz, 1H), 8.28 (dd, J = 2.0, 8.6 Hz, 1H), 7.54 - 7.46 (m, 3H), 7.45 - 7.41 (m, 1H), 7.33 - 7.27 (m, 2H), 3.88 (s, 3H); LC-MS: 97.44% at 2.676 min; m / z 313.2 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1 .2 mL / min (Gradient)]; HPLC: 95.36% at 6.71 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase- A: 0.05% TFA: ACN (95:05), Mobile Phasc-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 2: Synthesis of methyl 2-(allylthio)-4-oxo-3-phenyl-3,4-dihydroquinazoline-6- carboxylate (Compound 18)

[0171] Compound 18 was prepared from Compound 17 according to general procedure. White solid, Yield- 270 mg, 0.77 mmol, 59%.

[0172] 1H NMR (400 MHz, DMSO-d6) δ 8.62 (d, J = 1.8 Hz, 1H), 8.31 (dd, 7 = 2.1, 8.6 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.62 - 7.54 (m, 3H), 7.52 - 7.44 (m, 2H), 5.97 - 5.86 (m, 1H), 5.34 (dd, J = 1.6, 17.0 Hz, 1H), 5.20 - 5.06 (m, 1H), 3.90 (s, 3H), 3.85 (d, J = 7.0 Hz, 2H); ); LC-MS: 97.53% at 3.651 min; m / z 353.3 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 97.14% at 8.90 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 3: Synthesis of 2-(allylthio)-4-oxo-3-phenyl-3,4-dihydroquinazoIine-6-carboxylic acid (Compound 19)

[0173] To a stirred solution of Compound 18 (150 mg, 0.43 mmol) in ACN, water (1:1) was added Et3N (347 mg, 3.44 mmol) at RT and the reaction mixture was stirred at RT for 24 h. Progress of reaction was monitored by TLC. After completion of reaction, volatiles were removed under vacuum, residue was diluted with water (20 mL) and acidified to pH 2. The formed solid was collected by filtration and the solids and washed with water and dried under vacuum to afford crude product which was recrystallized from ethanol to afford 2-(allylthio)-4-oxo-3-phenyl-3,4- dihydroquinazoline-6-carboxylic acid (Compound 19) (48 mg, 0.14 mmol) as off white solid. Yield-33%

[0174] 1H NMR (400 MHz, DMSO-d6) δ 13.25 (br s, 1H), 8.62 (d, 7 = 1.7 Hz, 1H), 8.30 (dd, 7= 2.0, 8.6 Hz, 1H), 7.69 (d, 7= 8.6 Hz, 1H), 7.62 - 7.54 (m, 3H), 7.52 - 7.44 (m, 2H), 5.97 - 5.86 (m, 1H), 5.34 (dd, J = 1.2, 17.0 Hz, 1H), 5.13 (d, J = 10.0 Hz, 1H), 3.85 (d, 7= 7.0 Hz, 2H); LC- MS: 97.97% at 3.153 min; m / z 339.1 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 97.42% at 11.73 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 4: Synthesis of 2-(allylthio)-4-oxo-3-phenyl-3,4-dihydroquinazoline-6-carboxamide (Compound 20)

[0175] A solution of Compound 18 (120 mg, 0.34 mmol) in methanolic ammonia (10 mL) was stirred at 60 °C for 24 h. Progress of reaction was monitored by TLC. After completion of reaction, volatiles were removed under vacuum to afford crude product which was recrystallized from ethanol to afford 2-(allylthio)-4-oxo-3-phenyl-3,4-dihydroquinazoline-6-carboxamide (compound 20) (42 mg, 0.12 mmol) as white solid. Yield: 36%

[0176] 1H NMR (400 MHz, DMSO-d6) δ 8.62 (d, J = 2.0 Hz, 1H), 8.32 - 8.20 (m, 2H), 7.67 (d, J = 8.6 Hz, 1H), 7.61 - 7.54 (m, 3H), 7.52 - 7.43 (m, 3H), 5.97 - 5.86 (m, 1H), 5.34 (dd, J = 1.5, 17.0 Hz, 1H), 5.13 (td, J = 0.8, 10.0 Hz, 1H), 3.84 (d, J = 7.0 Hz, 2H); LC-MS: 97.87% at 2.800 min; m / z 337.9 [M+H]+[Column: Accucore C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 96.60% at 9.78 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phasc-A: 0.05% TFA: ACN (95:05), Mobile Phasc-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Experimental details for Compound 21:Step 1: Synthesis of 6-methyl-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 21)

[0177] Compound 21 was prepared from corresponding 2-amino-5-methylbenzoic acid and phenyisothiocyanate according to general procedure as off white solid. Yield- 160 mg, 0.60 mmol, 22.5%

[0178] 1H NMR (400 MHz, DMSO-d6) δ 12.98 (br s, 1H), 7.76 (br s, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.52 - 7.32 (m, 4H), 7.26 (d, J = 7.3 Hz, 2H), 2.38 (s, 3H); LC-MS: 99.08% at 2.866 min; m / z 269.0 [M+H]+ [Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Aq. NH4OAC, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.47% at 6.76 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A:0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min,Diluent: ACN: Water],Experimental details for Compounds 22, 23, 24 & 25:Step 1: Synthesis of 6-nitro-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound_22)

[0179] Compound 22 was prepared from corresponding 2-amino-5-nitrobenzoic acid and phenyisothiocyanate according to step 1 general procedure using t-butanol and Et3N (3.0) as pale yellow solid. Yield-660 mg, 2.20 mmol-40%.

[0180] 1H NMR (400 MHz, DMSO-d6) δ 13.46 (br s, 1H), 8.66 - 8.53 (m, 2H), 7.58 (d, J = 9.0 Hz, 1H), 7.54 - 7.47 (m, 2H), 7.46 - 7.39 (m, 1H), 7.31 (d, 7 = 7.3 Hz, 2H); LC-MS: 99.54% at 2.845 min; m / z 300.0 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 98.50% at 10.11 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 2: Synthesis of 2-(allylthio)-6-nitro-3-phenylquinazolin-4(3H)-one

[0181] 2-(allylthio)-6-nitro-3-phenylquinazolin-4(3H)-one was prepared from Compound 22 according to step 2 general procedure as pale yellow solid. Yield-68%

[0182] 1H NMR (500 MHz, DMSO-d6) δ 8.77 (d, J = 2.4 Hz, 1H), 8.58 (dd, J = 2.7, 8.9 Hz, 1H), 7.81 (d, J = 8.9 Hz, 1H), 7.64 - 7.56 (m, 3H), 7.54 - 7.46 (m, 2H), 5.96 - 5.88 (m, 1H), 5.36 (br d, J = 17.0 Hz, 1H), 5.15 (d, J = 10.1 Hz, 1H), 3.88 (d, J = 6.8 Hz, 2H); LC-MS: m / z 353.2 [M+H]+Step 3: Synthesis of 2-(allylthio)-6-amino-3-phenylquinazolin-4(3H)-one (Compound 23)

[0183] To a stirred solution of 2-(allylthio)-6-nitro-3-phenylquinazolin-4(3H)-one (600 mg, 1.76 mmol) in MeOH, THF, water (5:3:1) was added Zinc (8.8 mmol), ammonium chloride (17.6 mmol) at RT and the reaction mixture was stirred at 80 °C for 3 h. Progress of reaction was monitored by TLC. After completion of reaction, volatiles were removed under vacuum, residue was diluted with water (20 mL) and extracted with EtOAc (2 x 20 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude product was diluted with EtOAc, formed solid was filtered and residue was washed with hexane (20 mL) to afford 2- (allylthio)-6-amino-3-phenylquinazolin-4(3H)-one (Compound 23) (440 mg, 1.42 mmol) 80% Yield as pale yellow solid.

[0184] 1H NMR (400 MHz, DMSO-d6) δ 7.59 - 7.49 (m, 3H), 7.41 - 7.32 (m, 3H), 7.17 (d, J = 2.6 Hz, 1H), 7.09 (dd, J = 2.7, 8.7 Hz, 1H), 5.94 - 5.83 (m, 1H), 5.59 (s, 2H), 5.28 (dd, J= 1.7, 16.9 Hz, 1H), 5.16 - 5.05 (m, 1H), 3.75 (d, J = 7.0 Hz, 2H); LC-MS: 98.46% at 2.930 min; m / z 310.3 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phasc-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 99.57% at 9.22 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 4: Synthesis of 2-(allylthio)-6-(dimethylamino)-3-phenylquinazolin-4(3H)-one (Compound 24)

[0185] To a solution of Compound 23 (180 mg, 0.58 mmol) in ACN (5 mL) was added K2CO3(241 mg, 1.74 mmol) and Mel (206 mg, 1.45 mmol) at 0 °C and the reaction mixture was stirred at RT for 24 h. Progress of reaction was monitored by TLC. After completion, Volatiles were removed, residue was diluted with EtOAc (40 mL) and washed with water (20 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude product was purified by Combi flash chromatography (25% EtOAc in hexanes) to afford 2-(allylthio)-6- (dimethylamino)-3-phenylquinazolin-4(3H)-one (compound 24) (30 mg, 0.09 mmol) as pale yellow solid. Yield: 15%

[0186] 1H NMR (400 MHz, DMSO-d6) δ 7.60 - 7.48 (m, 4H), 7.44 - 7.32 (m, 3H), 7.15 (d, J= 3.1 Hz, 1H), 5.95 - 5.84 (m, 1H), 5.30 (dd, J= 1.7, 16.9 Hz, 1H), 5.15 - 5.05 (m, 1H), 3.78 (d, J= 7.0 Hz, 2H), 3.00 (s, 6H); LC-MS: 97.16% at 3.366 min; m / z 338.3 [M+H]+[Column: XBridgeBEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase- B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 95.30% at 8.24 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 g), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Step 5: Synthesis of N-(2-(alIylthio)-4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl)acetamide (Compound 25)

[0187] To a solution of Compound 23 (120 mg, 0.39 mmol) in DCM (5 mL) was added Et3N (79 mg, 0.78 mmol) and AcCl (33 mg, 0.43 mmol) at 0 °C and the reaction mixture was stirred at RT for 4 h. Progress of reaction was monitored by TEC. After completion, the reaction mixture was diluted with DCM (30 mL) and washed with water (2 x 20 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude product was purified by Combi flash chromatography (5% EtOAc in hexanes) to afford Synthesis of N-(2- (allylthio)-4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl)acetamide (Compound 25) (40mg, 0.11 mmol) as off white solid. Yield: 28%

[0188] 1H NMR (400 MHz, DMSO-d6) δ 10.28 (s, 1H), 8.36 (d, J = 2.4 Hz, 1H), 8.00 (dd, J = 2.4, 8.8 Hz, 1H), 7.67 - 7.52 (m, 4H), 7.50 - 7.37 (m, 2H), 5.95 - 5.84 (m, 1H), 5.31 (dd, 7= 1.5, 17.0 Hz, 1H), 5.11 (dt, J = 0.8, 10.0 Hz, 1H), 3.80 (d, J = 7.0 Hz, 2H), 2.08 (s, 3H); LC-MS: 99.81% at 3.091 min; m / z. 352.3 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 99.31% at 10.83 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 g), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN :0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Experimental details for Compound 26, 27, and 28:Step 1: Synthesis of 6-methoxy-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one(Compound 26)

[0189] Compound 26 was prepared from corresponding 2-amino-5-methoxybenzoic acid and phenyisothiocyanate according to step 1 general procedure. Off white solid, Yield-(140 mg, 0.43 mmol)-61%.

[0190] 1H NMR (400 MHz, DMSO-d6) δ 12.99 (s, 1H), 7.52 - 7.33 (m, 6H), 7.29 - 7.23 (m, 2H), 3.83 (s, 3H); LC-MS: 97.93% at 2.640 min; m / z 285.1 [M+H]+[Column: XBridge BEH C- 18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 98.80% at 6.49 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 2: Synthesis of 2-(allylthio)-6-methoxy-3-phenylquinazolin-4(3H)-one (Compound 27)

[0191] Compound 27 was prepared from Compound 26 according to step 2 general procedure as off white solid. Yield-(140 mg, 0.43 mmol), 61%.

[0192] 1H NMR (400 MHz, DMSO-d6) δ 7.65 - 7.51 (m, 4H), 7.49 - 7.34 (m, 4H), 5.95 - 5.85(m, 1H), 5.31 (d, J= 17.2 Hz, 1H), 5.11 (d, 7= 9.8 Hz, 1H), 3.86 (s, 3H), 3.80 (d, 7= 7.0 Hz, 2H); LC-MS: 97.53% at 3.638 min; m / z 325.3 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 99.13% at 8.82 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B:ACN :0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 1: Synthesis of 2-(allylthio)-6-hydroxy-3-phenylquinazolin-4(3H)-one (Compound 28)

[0193] To a solution of Compound 27 (80 mg, 0.24 mmol) in DCM (5 mF) was added BBr3(IM DCM) (4.47 g, 79.7 mmol) at 0 °C and the reaction mixture was stirred at RT for 16 h. Progress of reaction was monitored by TLC. After completion, the reaction mixture was quenched with methanol (2 mF) and diluted with DCM (40 mF) and washed with water (3 x 30 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude was purified by Combi flash chromatography (30% EtOAc in hexanes) to afford 2-(allylthio)-6-hydroxy-3-phenylquinazolin-4(3H)-one (Compound 28) (25 mg, 0.08 mmol) as off white solid. Yield: 33%.

[0194] 1H NMR (500 MHz, DMSO-d6) δ 10.02 (s, 1H), 7.60 - 7.47 (m, 4H), 7.45 - 7.35 (m, 3H), 7.28 (dd, J= 2.8, 8.8 Hz, 1H), 5.93 - 5.85 (m, 1H), 5.30 (d, J= 17.0 Hz, 1H), 5.10 (d, J= 9.8 Hz, 1H), 3.78 (d, J = 6.8 Hz, 2H); LC-MS: 97.68% at 3.161 min; m / z 311.3 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq. TFA + 5% ACN, Mobile Phase-B: ACN + 5% 0.025% Aq. TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 98.56% at 11.31 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN :0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 29:Step 1: Synthesis of 2-(Allylthio)-4-oxo-3-phenyl-3,4-dihydroquinazolin-6-yl acetate(Compound 29):

[0195] To a solution of Compound 28 (120 mg, 0.37 mmol) in DCM (5 mL) was added Et3N (74.7 mg, 0.74 mmol) and AcCI (32 mg, 0.41 mmol) at 0 °C and the reaction mixture was stirred at RT for 4 h. Progress of reaction was monitored by TLC. After completion, the reaction mixture was diluted with DCM (30 mL) and washed with water (3 x 20 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude product was purified by Combi flash chromatography (5% EtOAc in hexanes) to afford 2-(allylthio)-4-oxo-3- phenyl-3,4-dihydroquinazolin-6-yl acetate (Compound 29) (10 mg, 0.03 mmol) as off white solid. Yield-7.5%.

[0196] 1H NMR (400 MHz, DMSO-d6) δ 7.79 (d, J= 2.7 Hz, 1H), 7.71 - 7.65 (m, 1H), 7.64 - 7.53 (m, 4H), 7.49 - 7.42 (m, 2H), 5.96 - 5.86 (m, 1H), 5.33 (dd, J= 1 .5, 17.0 Hz, 1H), 5.18 - 5.07 (m, 1H), 3.82 (d, J= 7.0 Hz, 2H), 2.31 (s, 3H); LC-MS: 97.17% at 3.289 min; m / z 353.2 [M+H]+[Column: XSelect CSH C-18 (3.0x50 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 96.47% at 8.31 min[Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 30:Step 1: Synthesis of 6-Bromo-3-(4-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 30)

[0197] Compound 30 was prepared from corresponding 2-amino-5-bromobcnzoic acid and 1- chloro-4-isothiocyanatobenzene according to step 1 general procedure. (405 mg, 1.10 mmol) 47%.

[0198] 1H NMR (500 MHz, DMSO-d6) δ 13.15 (s, 1H), 8.00 (d, J = 2.1 Hz, 1H), 7.94 (dd, J = 2.2, 8.8 Hz, 1H), 7.53 (d, J = 8.6 Hz, 2H), 7.37 (d, 7 = 8.6 Hz, 1H), 7.32 (d, J = 8.6 Hz, 2H); LC-MS: 98.71% at 2.870 min; m / z 366.8 [M]’ [Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 98.72% at 7.85 min [Column: XSELECT CSH C18 150 X 4.6 mm, 3.5μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Experimental details for Compound 31:Step 1: Synthesis of 6-bromo-3-(3-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)- one(Compound 31)

[0199] Compound 31 was prepared from corresponding 2-amino-5-bromobenzoic acid and 1- chloro-3-isothiocyanatobenzene according to step 1 general procedure. Yield (120 mg, 0.32 mmol), 35%.

[0200] 1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 8.01 (d, J = 2.3 Hz, 1H), 7.96 (dd, J = 2.3, 8.7 Hz, 1H), 7.55 - 7.44 (m, 3H), 7.39 (d, J = 8.7 Hz, 1H), 7.29 (dt, J = 1.9, 7.0 Hz, 1H); LC-MS: 99.63% at 2.863 min; m / z 366.8 [M]’ [Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 95.03% at 7.659 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase- A:0.05% TFA in water : ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Experimental details for Compound 32 and 33:Step 1: Synthesis of 6-bromo-3-(2-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 32)

[0201] Compound 32 was prepared from corresponding 2-amino-5-bromobenzoic acid and 1- chloro-2-isothiocyanatobenzene according to step 1 general procedure. (72 mg, 0.196 mmol) 20%.

[0202] 1H NMR (500 MHz, DMSO-d6) δ 13.30 (s, 1H), 8.05 (d, J = 2.1 Hz, 1H), 8.00 (dd, J = 2.2, 8.8 Hz, 1H), 7.66 - 7.59 (m, 1H), 7.52 - 7.44 (m, 3H), 7.42 (d, J = 8.6 Hz, 1H); LC-MS: 99.15% at 2.984 min; m / z 368.0 [M]+[Column: XSelect CSH C-18 (3.0x50 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.54% at 11.66 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Step 2: Synthesis of 2-(allylthio)-6-bromo-3-(2-chlorophenyl)quinazolin-4(3H)-one (Compound 33)

[0203] Compound 33 was prepared from Compound 32 according to step 2 general procedure. (108 mg, 0.266 mmol) 56%

[0204] 1H NMR (500 MHz, DMSO-d6) δ 8.18 (d, 7 = 2.4 Hz, 1H), 8.02 (dd, 7 = 2.4, 8.6 Hz, 1H), 7.75 (d, 7= 8.0 Hz, 1H), 7.71 - 7.66 (m, 1H), 7.63 - 7.56 (m, 3H), 5.94 - 5.86 (m, 1H), 5.35(d, J = 17.0 Hz, 1H), 5.14 (d, J= 9.8 Hz, 1H), 3.93 - 3.74 (m, 2H); LC-MS: 98.47% at 3.524 min; m / z 407.8 [M]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.85% at 11.18 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water].Experimental details for Compound 34:Step 1: Synthesis of 6-bromo-3-(3-methoxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)- one (Compound 34)

[0205] Compound 34 was prepared from corresponding 2-amino-5-bromobenzoic acid and 1- isothiocyanato-3-methoxybenzene according to step 1 general procedure. Yield (170 mg, 0.469 mmol) 34%.

[0206] 1H NMR (400 MHz, DMSO-d6) δ = 13.11 (s, 1H), 8.00 (d, J = 2.2 Hz, 1H), 7.95 (dd, J = 2.3, 8.7 Hz, 1H), 7.43 - 7.34 (m, 2H), 6.98 (ddd, J = 0.1, 2.6, 8.3 Hz, 1H), 6.90 (t, J= 2.1 Hz, 1H), 6.85 (ddd, J = 0.9, 1.7, 7.8 Hz, 1H), 3.76 (s, 3H); LC-MS: 98.91% at 2.669 min; m / z 364.8 [M+2]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.74% at 10.686 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water].

[0207] Experimental details for Compound 35:Step 1: Synthesis of 4-(4-isothiocyanatophenyl)morpholine

[0208] 4-(4-isothiocyanatophenyl)morpholine was prepared from 4-morpholinoaniline. To a solution of 4-morpholinoaniline(500 mg, 2.84 mmol) in DCM (15 mL) was added triethylamine (315 g, 3.12 mmol) and Thiophosgene (393 mg, 3.42 mmol) at 0 °C and the resulting reaction mixture was stirred for 3 h at same temperature. Progress of the reaction was monitored by TLC. After completion of starling material, reaction mixture was quenched and diluted with water (50 mL) and extracted with dichloromethane (3 x 30 mL). The combined organic layer was washed dried over anhydrous sodium sulphate and dried invacuo to afford crude product (4-(4- isothiocyanatophenyl)morpholine) and it was directly used or next step without any further purification. Yield (110 mg, 0.5 mmol) 89%.

[0209] 1H NMR (400 MHz, DMSO-d6) δ 7.30 (d, J = 9.0 Hz, 2H), 6.96 (d, J = 9.0 Hz, 2H), 3.78 - 3.66 (m, 4H), 3.22 - 3.06 (m, 4H); LC-MS: m / z 221.0 [M+H]+Step 2: Synthesis of 6-bromo-3-(4-morpholinophenyl)-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one

[0210] 6-bromo-3-(4-morpholinophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one was prepared from corresponding 4-(4-isothiocyanatophenyl)morpholine and 2-amino-5- bromobenzoic acid according to step 1 general procedure. Yield (35 mg, 0.08 mmol) 16%.

[0211] 1H NMR (400 MHz, DMSO-d6) δ 13.06 (br s, 1H), 7.99 (br d, J = 2.0 Hz, 1H), 7.96 - 7.89 (m, 1H), 7.37 (br d, J= 8.8 Hz, 1H), 7.12 - 7.03 (m, 2H), 7.02 - 6.94 (m, 2H), 3.76 (t, J= 4.8 Hz, 4H), 3.17 (t, J = 4.8 Hz, 4H); LC-MS: 96.75% at 2.560 min; m / z 419.2 [M+2]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 95.85% at 6.83 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase- B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 3: Synthesis of 2-(allylthio)-6-bromo-3-(4-morpholinophenyl)quinazolin-4(3H)-one (Compound 35)

[0212] Compound 35 was prepared from 6-bromo-3-(4-morpholinophenyl)-2-thioxo-2,3- dihydroquinazolin-4(lH)-one according to step 2 general procedure. Yield (35 mg, 0.08 mmol) 45%.

[0213] 1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 2.2 Hz, 1H), 7.96 (dd, J = 2.3, 8.6 Hz,1H), 7.57 (d, J = 8.6 Hz, 1H), 7.23 (br d, J = 8.8 Hz, 2H), 7.05 (br d, J = 8.9 Hz, 2H), 5.95 - 5.86(m, 1H), 5.32 (br d, J = 17.7 Hz, 1H), 5.12 (br d, J = 9.9 Hz, 1H), 3.84 - 3.70 (m, 6H), 3.26 - 3.17 (m, 4H); LC-MS: 98.48% at 3.349 min; m / z 459.9 [M+2]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.66% at 9.951 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Experimental details for Compound 36 and 37:Step 1: Synthesis of 6-bromo-3-(pyridin-3-yl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 36)

[0214] Compound 36 was prepared from corresponding 2-amino-5-bromobenzoic acid and 3- isothiocyanatopyridine according to step 1 general procedure. Yield (160 mg, 0.48 mmol) 34%.

[0215] 1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1H), 8.60 (dd, J = 1.5, 4.8 Hz, 1H), 8.49 (d, J = 2.0 Hz, 1H), 8.03 (d, J = 2.2 Hz, 1H), 7.98 (dd, J = 2.3, 8.7 Hz, 1H), 7.81 - 7.74 (m, 1H), 7.59 - 7.51 (m, 1H), 7.41 (d, J = 8.7 Hz, 1H); LC-MS: 94.35% at 2.235 min; m / z 334.0 [M]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.83% at 7.92 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Step 2: Synthesis of 2-(allylthio)-6-bromo-3-(pyridin-3-yl)quinazolin-4(3H)-one (Compound 37)

[0216] Compound 37 was prepared from Compound 36 according to step 2 general procedure. Yield (65 mg, 0.174 mmol) 48%.

[0217] 1H NMR (400 MHz, DMSO-d6) δ 8.74 (dd, J = 1.5, 4.8 Hz, 1H), 8.69 (d, J = 2.1 Hz, 1H), 8.16 (d, J= 2.3 Hz, 1H), 8.05 - 7.96 (m, 2H), 7.71 - 7.56 (m, 2H), 5.96 - 5.86 (m, 1H), 5.35 (dd, J = 1.5, 17.0 Hz, 1H), 5.14 (dt, J = 0.7, 10.0 Hz, 1H), 3.86 (d, J = 7.0 Hz, 2H); LC-MS:99.69% at 3.141 min; m / z 374.1 [M]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM NfEOAc, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.77% at 8.26 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A:0.05% TFA in water : ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Experimental details for Compound 38 and 39:Step 1: Synthesis of ethyl 2-amino-5-bromobenzoate

[0218] To a solution of 2-amino-5-bromobenzoic acid (2g, 9.30 mmol) in ethanol was added H2SO4(1.82 g, 18.6 mmol) at 0 °C and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting material, reaction mixture was concentrated in vacuo to get crude product. Crude product was diluted with saturated sodium bicarbonate solution (70 mL), extracted with ethyl acetate (3x80mL). The combined organic layer was dried over anhydrous sodium sulphate and concentrated to afford ethyl 2-amino- 5-bromobenzoate (1.8 g, 7.40 mmol) as off white solid. 79%.

[0219] 1H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 2.4 Hz, 1H), 7.37 (dd, J - 2.5, 8.9 Hz, 1H), 6.86 - 6.71 (m, 3H), 4.26 (q, J = 7.1 Hz, 2H), 1.30 (t, J = 7.1 Hz, 3H); LC-MS: m / z 244.1 [M]+Step 2: Synthesis of ethyl 5-bromo-2-isothiocyanatobenzoate

[0220] Ethyl 5-bromo-2-isothiocyanatobenzoate was prepared from ethyl 2-amino-5- bromobenzoate (1g) in the similar procedure according to step-1 as 4-(4- isothiocyanatophenyl)morpholine using DIPEA, DCM. Yield (1 g, 3.50 mmol) 85% pale yellow solid.

[0221] 1H NMR (500 MHz, DMSO-d6) δ 8.06 (d, J = 2.4 Hz, 1H), 7.89 (dd, J = 2.4, 8.6 Hz, 1H), 7.55 (d, J = 8.6 Hz, 1H), 4.35 (q, J = 7.1 Hz, 2H), 1.35 (t, J = 7.1 Hz, 3H); LC-MS: m / z 286.0 [M]+Step 3: Synthesis of 6-bromo-3-(pyridin-2-yl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 38)

[0222] To a solution of ethyl 5-bromo-2-isothiocyanatobenzoate in ethanol was added triethylamie (3 eq) and pyridin-2-amine (1.1 eq) at room temperature and the resulting reaction mixture was stirred at 80 °C for 72 h. Progress of the reaction was monitored by TLC. After completion of starling material, reaction mixture was cooled to room temperature, the precipitated solid was filtered and residue was washed with CH2CI2(30 mL) to afford Compound 38 (335 mg, 1 mmol) as pale brown solid. 28%

[0223] 1H NMR (400 MHz, DMSO-d6) δ 13.22 (br s, 1H), 8.59 (dd, J= 2.0, 5.0 Hz, 1H), 8.07 - 7.95 (m, 3H), 7.51 - 7.46 (m, 2H), 7.41 (d, J = 8.8 Hz, 1H); LC-MS: 93.18% at 2.210 min; m / z 333.9 [M]+[Column: Kinctcx EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phasc-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 96.94% at 6.00 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Step 4: Synthesis of 2-(allylthio)-6-bromo-3-(pyridin-2-yl)quinazolin-4(3H)-one (Compound 39)

[0224] Compound 39 was prepared from Compound 38 according to step 2 general procedure Yield (105 mg, 0.281 mmol) 93%. Off white solid.

[0225] 1H NMR (500 MHz, DMSO-d6) δ 8.68 (d, J= 3.9 Hz, 1H), 8.16 (d, J = 2.1 Hz, 1H), 8.10 (dt, J = 1.6, 7.7 Hz, 1H), 8.01 (dd, J = 2.4, 8.6 Hz, 1H), 7.70 (d, J = 7.7 Hz, 1H), 7.66 - 7.58 (m, 2H), 5.94 - 5.86 (m, 1H), 5.33 (dd, J = 1.2, 17.0 Hz, 1H), 5.13 (d, J = 10.1 Hz, 1H), 3.86 (d, J = 7.1 Hz, 2H); LC-MS: 96.81% at 3.359 min; m / z 374.1 [M]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.93% at 8.46 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A:0.05% TFA in water : ACN (95:05), Mobile Phase- B:ACN :0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Experimental details for Compounds 40 and 41:Step 1: Synthesis of 6-bromo-3-cyclohexyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 40)

[0226] Compound 40 was prepared from corresponding 2-amino-5-bromobenzoic acid and isothiocyanatocyclohexane according to step 1 general procedure using t-butanol and Et3N. Yield (120 mg, 0.355 mmol) 15%

[0227] 1H NMR (500 MHz, DMSO-d6) δ 12.96 (br s, 1H), 7.98 (d, 7= 2.1 Hz, 1H), 7.88 (dd, 7 = 2.2, 8.8 Hz, 1H), 7.31 (d, 7= 8.6 Hz, 1H), 5.70 (br s, 1H), 2.46 - 2.32 (m, 2H), 1.81 (br d, 7 =13.1 Hz, 2H), 1.66 (br d, J = 8.6 Hz, 3H), 1.37 - 1.11 (m, 3H); LC-MS: 98.80% at 3.644 min; m / z338.1 [M]‘ [Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.09% at 10.35 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A:0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water].Step 2: Synthesis of 2-(allylthio)-6-bromo-3-cyclohexylquinazolin-4(3H)-one (Compound 41)

[0228] Compound 41 was prepared from Compound 40 according to step 2 general procedure. Yield (25 mg, 0.06 mmol) 18%

[0229] 1H NMR (400 MHz, DMSO-d6) δ 8.10 (d, J = 2.3 Hz, 1H), 7.90 (dd, J = 2.4, 8.7 Hz, 1H), 7.49 (d, 7= 8.7 Hz, 1H), 6.04 - 5.93 (m, 1H), 5.50 - 5.36 (m, 1H), 5.24 - 5.14 (m, 1H), 4.17 (br s, 1H), 3.95 (d, J = 7.0 Hz, 2H), 2.55 (br d, 7 = 2.7 Hz, 1H), 1.84 (br d, 7 = 13.0 Hz, 2H), 1.77 - 1.61 (m, 3H), 1.40 - 1.11 (m, 4H); LC-MS: 97.45% at 4.785 min; m / z 379.1 [M]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: >99.00% at 10.688 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A:0.05% Ammonia in 2.5 mM Ammonium bicarbonate, Mobile Phase-B:ACN, Flow: 1.7 mL / min, Diluent: ACN:Water].Experimental details for Compound 42:Step 1: Synthesis of 3-benzyl-6-bromo-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 42)

[0230] Compound 42 was prepared from corresponding 2-amino-5-bromobenzoic acid and (isothiocyanatomethyl)benzene according to step 1 general procedure. Yield (190 mg, 0.549 mmol) 39%.

[0231] 1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 8.03 (d, J = 2.2 Hz, 1H), 7.93 (dd, J = 2.3, 8.8 Hz, 1H), 7.37 (d, J= 8.7 Hz, 1H), 7.34 - 7.20 (m, 5H), 5.65 (s, 2H); LC-MS: 99.16% at 3.925 min; m / z 346.6 [M]- [Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Aq NH4OAC, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.96% at 8.46 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A:0.05% TFA in water : ACN (95:05), Mobile Phase-B:ACN :0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water].Experimental details for Compounds 43, 44, 45 & 46:Step 1: Synthesis of ethyl 2-(6-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)acetate (Compound 43)

[0232] Compound 43 was prepared from corresponding 2-amino-5-bromobenzoic acid and ethyl 2-isothiocyanatoacetate according to step 1 general procedure. (1.2 g) 50%

[0233] 1H NMR (500 MHz, DMSO-d6) δ 13.28 (s, 1H), 8.06 (d, J = 2.1 Hz, 1H), 7.97 (dd, J = 2.2, 8.8 Hz, 1H), 7.38 (d, 7 = 8.6 Hz, 1H), 5.17 (s, 2H), 4.16 (q, J = 7.1 Hz, 2H), 1.21 (t, 7= 7.1 Hz, 3H); LC-MS: 95.00% at 2.683 min; m / z 342.9 [M]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.58% at 7.32 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Step 2: Synthesis of ethyl 2-(2-(allylthio)-6-bromo-4-oxoquinazolin-3(4H)-yl)acetate (Compound 44)

[0234] Compound 44 was prepared from Compound 43 according to step 2 general procedure.(1.1 g) 91.6%

[0235] 1H NMR (500 MHz, DMSO-d6) δ 8.14 (d, J = 2.4 Hz, 1H), 7.96 (dd, J = 2.2, 8.8 Hz, 1H), 7.56 (d, 7= 8.6 Hz, 1H), 5.98 - 5.90 (m, 1H), 5.50 - 5.32 (m, 1H), 5.17 (d, 7 = 10.1 Hz, 1H), 4.86 (s, 2H), 4.17 (q, 7 = 7.0 Hz, 2H), 3.97 (d, 7= 6.8 Hz, 2H), 1.19 (t, 7= 7.0 Hz, 3H); LC-MS: 99.76% at 3.369 min; m / z 383.0 [M]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25 mM Ammonium Formate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.26% at 9.69 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water].Step 3: Synthesis of 2-(2-(allylthio)-6-bromo-4-oxoquinazolin-3(4H)-yl)acetic acid (Compound 45)

[0236] Compound 44 (500 mg, 1.30 mmole) in THF and H2O (5 mF) was added LiOH.H2O (65 mg, 1.56 mmol) at 0 °C and the reaction mixture was stirred at RT for 16 h. Progress of reaction was monitored by TLC. After completion, THF was distilled on vacuum, aqueous layer was pH=4 adjusted with 2N aq.HCl, stirred for 5 min, solid was precipitated. Resultant solids were filtered and triturated with H2O and dried under vacuum to afford 2-(2-(allylthio)-6-bromo-4- oxoquinazolin-3(4H)-yl) acetic acid (Compound 45) (400 mg, 1.13 mmol, 86.3%) as a white solid.

[0237] 1H NMR (500 MHz, DMSO-d6) δ 13.43 (s, 1H), 8.16 (d, J = 2.1 Hz, 1H), 7.97 (dd, 7 = 2.4, 8.6 Hz, 1H), 7.57 (d, J = 8.6 Hz, 1H), 6.01 - 5.92 (m, 1H), 5.42 (d, 7 = 17.5 Hz, 1H), 5.19 (d, J = 10.1 Hz, 1H), 4.78 (s, 2H), 3.98 (d, J = 6.8 Hz, 2H); LC-MS: 98.98% at 2.828 min; m / z 355.8 [M]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.25% Formicacid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 96.29% at 8.17 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A:0.05% TFA in water : ACN (95:05), Mobile Phase-B:ACN :0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Step 5: Synthesis of 2-(2-(aIlylthio)-6-bromo-4-oxoquinazolin-3(4H)-yl)-N,N- dimethylacetamide (Compound 46)

[0238] Compound 45 (250 mg, 0.70 mmol) in DMF (5 mL) was added EDC.HCl (200 mg, 1.04 mmol), DMAP (254 mg, 2.09 mmol), N,N-dimethyl amine hydrochloride salt (68.3 mg, 0.84 mmol) at RT and the reaction mixture was stirred at RT for 16 h. Progress of reaction was monitored by TLC. After completion, poured in to ice cold water, stirred for 5 min, and solid was precipitated. Resultant solids were filtered and triturated with CH2CI2, hexane and dried under vacuum to afford 2-(2-(allylthio)-6-bromo-4-oxoquinazolin-3(4H)-yl)-N,N-dimethylacetamide (Compound 46) (130 mg, 0.34 mmol, 48%) as a off white solid.

[0239] 1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 2.3 Hz, 1H), 7.96 (dd, J = 2.4, 8.7 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 6.01 - 5.90 (m, 1H), 5.41 (dd, J = 1.3, 17.0 Hz, 1H), 5.18 (d, J = 10.0 Hz, 1H), 4.96 (s, 2H), 3.96 (d, J = 6.8 Hz, 2H), 3.11 (s, 3H), 2.86 (s, 3H); LC-MS: 99.30% at 2.807 min; m / z 381.9 [M]+[Column: Kinetex EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase- A: 0.25% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.20% at 7.58 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Experimental details for Compound 47:Step 1: Synthesis of 6-bromo-3-phenyl-2-thioxo-2, 3-dihydroquinazolin-4(lH)-one

[0240] 6-bromo-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one was prepared from corresponding 2-amino-5-bromobenzoic acid and isothiocyanatobenzene according to step 1 general procedure. (6.5 g, 19.5 mmol) 42%.

[0241] 1H NMR (400 MHz, DMSO-d6) δ 13.13 (s, 1H), 8.01 (d, J = 2.2 Hz, 1H), 7.95 (dd, J = 8.7, 2.3 Hz, 1H), 7.51 - 7.45 (m, 2H), 7.44 - 7.38 (m, 2H), 7.30 - 7.25 (m, 2H); LC-MS: 99.64% at 2.850 min; m / z 335.0 [M+2] [Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)];Step 2: Synthesis of 6-bromo-3-phenyl-2-(propylthio) quinazolin-4(3H)-one (Compound 47)

[0242] Compound 47 was prepared from 6-bromo-3-phenyl-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one by using 1 -bromopropane according to step 2 general procedure. (45 mg, 0.12 mmol) 75%.

[0243] 1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 2.2 Hz, 1H), 7.96 (dd, J = 2.4, 8.7 Hz, 1H), 7.59 - 7.54 (m, 4H), 7.47 - 7.42 (m, 2H), 3.14 - 3.08 (m, 2H), 1.69 - 1.60 (m, 2H), 0.96 - 0.89 (m, 3H); LC-MS: 99.54% at 3.856 min; m / z 375.1 [M+H]+[Column: XBridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 97.53% at 11.51 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in Water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in Water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 48:Step: Synthesis of 6-bromo-3-phenyl-2-((pyridin-4-ylmethyl) thio) quinazolin-4(3H)-one (Compound 48)

[0244] Compound 48 was prepared from 6-bromo-3-phenyl-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one by using 4-(chloromethyl) pyridine hydrochloride according to step 2 general procedure. (40 mg, 0.094 mmol) 31%

[0245] 1H NMR (400 MHz, DMSO-d6) δ 8.47 (d, J = 5.9 Hz, 2H), 8.14 (d, J = 2.3 Hz, 1H), 7.99 (dd, J = 8.7, 2.3 Hz, 1H), 7.64 (d, J = 8.7 Hz, 1H), 7.58 - 7.53 (m, 3H), 7.49 - 7.43 (m, 4H), 4.39 (s, 2H); LC-MS: 99.16% at 6.068 min; m / z 424.1 [M+2]+[Column: X Bridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN,Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.57% at 6.62 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 49:Step: Synthesis of 6-bromo-2-((3-hydroxypropyI) thio)-3-pheny!quinazoIin-4(3H)-one(Compound 49)

[0246] Compound 49 was prepared from 6-bromo-3-phenyl-2-thioxo-2,3-dihydroquinazolin- 4(lH)-oneby using 3-bromopropan-l-ol according to step 2 general procedure. (60 mg, 0.153 mmol) 51%

[0247] 1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 2.4 Hz, 1H), 7.97 (dd, J = 8.7, 2.4 Hz, 1H), 7.58 - 7.54 (m, 4H), 7.46 - 7.43 (m, 2H), 4.53 (t, J = 5.2 Hz, 1H), 3.45 (q, J = 6.1 Hz, 2H), 3.16 (t, J = 7.2 Hz, 2H), 1.81 - 1.73 (m, 2H);

[0248] LC-MS: 99.75% at 3.283 min; m / z 392.9 [M+H]+[Column: X Bridge BEH C-18 (3.0X50 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq TFA+5% ACN, Mobile Phase-B: ACN+ 5% 0.025% Aq TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 99.86% at 7.38 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in Water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water]Experimental details for Compound 50:Step: Synthesis of 2-((2-(allylthio)-4-oxo-3-phenyl-3, 4-dihydroquinazolin-6-yl) oxy) acetamide (Compound 50)

[0249] Compound 28 was dissolved in acetone and to this mixture was added K2CO3(3 eq) and 2-chloroacetamide (1.2 eq) at RT and stirred for 6h at 60°C. The progress of the reaction was monitored by TLC. After completion of the reaction mixture was concentrated to afford crude product which was purified by column chromatography to afford Compound 50 (30 mg, 0.087 mmol) 25% as off white solid.

[0250] 1H NMR (500 MHz, DMSO-d6) δ 7.61 (d, J = 8.9 Hz, 2H), 7.57 - 7.53 (m, 3H), 7.51 - 7.37 (m, 5H), 5.94-5.86 (m, 1H), 5.31 (d, J = 17.0 Hz, 1H), 5.11 (d, J = 9.8 Hz, 1H), 4.55 (s, 2H), 3.80 (d, J - 6.8 Hz, 2H); LC-MS: 92.81% at 3.630 min; m / z 368.2 [M+H]+[Column: X Bridge BEH C-18 (3.0 X 50 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase- B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 95.58% at 8.65 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 51:Synthesis of tert-butyl 3-((2-(allylthio)-4-oxo-3-phenyl-3,4-dihydroquinazolin-6- yl)oxy)propanoate (Compound 51)

[0251] To a solution of Compound 28 (250 mg, 0.80 mmol) in CH3CN (10 mL) was added Et3N (5 eq) and t-Butylacrylate (1.5 eq) slowly at RT and the reaction mixture was stirred at 160 °C for 16 h in microwave irradiation. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ice cold water (30 mL) and extracted with EtOAc (3x25 mL), combined organic layer was dried over anhydrous sodium sulfate and concentrated to afford which was purified by column chromatography to afford compound 51(55 mg, 0.125 mmol) 15% as pale yellow liquid.

[0252] LC-MS: 99.40% at 3.593 min; m / z 439.2 [M+H]+[Column: Xbridge BEH C- 18(3.0X50 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradicnt);Experimental details for Compound 52:Synthesis of 2-(allylthio)-6-(2-bromoethoxy)-3-phenylquinazolin-4(3H)-one (Compound 52)

[0253] Compound 52 (200 mg, 0.645 mol) was prepared from Compound 28 by using 1,2- dibromoethane using acetone as solvent at RT according to similar procedure as compound 50 (90 mg, 0.216 mmol) 33%.

[0254] 1H NMR (500 MHz, DMSO-d6) δ 7.65 - 7.54 (m, 4H), 7.51 - 7.40 (m, 4H), 5.94 - 5.86 (m, 1H), 5.32 (d, J = 17.8 Hz, 1H), 5.11 (d, J = 10.1 Hz, 1H), 4.44 (t, J = 5.2 Hz, 2H), 3.86 - 3.77 (m, 4H); LC-MS: 96.42% at 3.416 min; m / z 417.1 [M+H]+[Column: EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 95.70% at 9.724 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA in Water: ACN (95:05), Mobile Phase-B: ACN: 0.05% TFA in Water (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 53:Step 1: Synthesis of 3-(2-chlorophenyl)-6-methoxy-2-thioxo-2,3-dihydroquinazolin-4(lH)- one

[0255] 3-(2-chlorophenyl)-6-methoxy-2-thioxo-2,3-dihydroquinazolin-4(lH)-one was prepared from corresponding 2-amino-5-methoxybenzoic acid and l-chloro-2- isothiocyanatobenzene according to step 1 general procedure. (185 mg, 0.581 mmol) 19%.

[0256] 1H NMR (400 MHz, DMSO-d6) δ 3.84 (s, 3 H) 7.38 (d, J=2.20 Hz, 1 H) 7.44 - 7.49(m, 5 H) 7.59 - 7.64 (m, 1 H) 13.14 (s, 1 H); LC-MS: 98.70% at 2.86 min; m / z 319.2 [M+H] [Column: X Bridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq TFA + 5%ACN„ Mobile Phase-B: ACN+ 5% 0.025% Aq TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 98.79% at 8.55 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Step 2: Synthesis of 2-(allylthio)-3-(2-chIorophenyl)-6-methoxyquinazolin-4(3H)-one (Compound 53)

[0257] Compound 53 was prepared from 3-(2-chlorophenyl)-6-methoxy-2-thioxo-2,3- dihydroquinazolin-4(lH)-one according to step 2 general procedure. (100 mg, 0.279 mmol) 74%.

[0258] 1H NMR (400 MHz, DMSO-d6) δ 3.83 (t, J=6.97 Hz, 2 H) 3.87 (s, 3 H) 5.12 (dd, J=9.96, 1.65 Hz, 1 H) 5.31-5.35 (m, 1 H) 5.86-5.94 (m, 1 H) 7.44 - 7.49 (m, 2 H) 7.53 - 7.68 (m, 4 H) 7.73 (dd, J=7.89, 1.41 Hz, 1 H); LC-MS: 99.51% at 3.72 min; m / z 359.2 [M+H] [Column: X Bridge BEH C-18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 0.025% Aq TFA + 5% ACN, Mobile Phase-B: ACN+ 5% 0.025% Aq TFA, Flow Rate: 1.2 mL / min (Gradient)]; HPLC: 98.33% at 8.47 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phasc-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound_54:Synthesis of 3-(3-chlorophenyl)-6-methoxy-2-thioxo-2,3-dihydroquinazoIin-4(lH)-one (Compound 54)

[0259] Compound 54 was prepared from corresponding 2-amino-5-methoxybenzoic acid and l-chloro-3-isothiocyanatobenzene according to step 1 general procedure. Yield (412 mg, 1.29 mmol), 43%.

[0260] 1H NMR (400 MHz, DMSO-d6) δ 3.83 (s, 3 H) 7.28-7.31 (m, 1 H) 7.36 (dd, J=2.14, 0.92 Hz, 1 H) 7.41 - 7.52 (m, 5 H) 13.04 (s, 1 H); LC-MS: 98.92% at 2.60 min; m / z 319.0 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase- B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.51% at 8.88 min [Column: XSELECTCSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B:ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 55:Step 1: Synthesis of ethyl 2-(6-methoxy-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)- yl)acetate

[0261] Ethyl 2-(6-methoxy-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)acetate was prepared from corresponding 2-amino-5-methoxybenzoic acid and ethyl 2-isothiocyanatoacetate according to step 3 general procedure. Yield (513 mg, 1.744 mmol) 30%.

[0262] 1H NMR (500 MHz, DMSO-d6) δ 1 .19 (t, J=7.14 Hz, 3 H) 3.83 (s, 3 H) 4.14 (q, J=7.14 Hz, 2 H) 5.19 (s, 2 H) 7.35 - 7.45 (m, 3 H) 13.11 (s, 1 H); LC-MS: 97.16% at 2.39 min; m / z 295.0 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 97.87% at 8.11 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 2: Synthesis of ethyl 2-(2-(allylthio)-6-methoxy-4-oxoquinazolin-3(4H)-yl)acetate (Compound 55)

[0263] Compound 55 was prepared from ethyl 2-(6-methoxy-4-oxo-2-thioxo- 1 ,4- dihydroquinazolin-3(2H)-yl)acetate according to step 4 general procedure. Yield (461 mg, 1.38 mmol) 81%.

[0264] 1H NMR (500 MHz, DMSO-d6) δ 1.21 (t, J=7.14 Hz, 3 H) 3.87 (s, 3 H) 3.96 (d, J=7.14 Hz, 2 H) 4.18 (q, J=7.14 Hz, 2 H) 4.88 (s, 2 H) 5.17 (d, J=10.11 Hz, 1 H) 5.40 (dd, J=16.95, 1.19 Hz, 1 H) 5.99-5.93 (m, 1 H) 7.42 - 7.46 (m, 2 H) 7.57 (d, J=8.33 Hz, 1 H); LC-MS: 99.43% at 3.025 min; m / z 335.0 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.62% at 10.73 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 56:Step 1: Synthesis of 3-benzyl-6-methoxy-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 56)

[0265] Compound 56 was prepared from corresponding 2-amino-5 -methoxybenzoic acid and (isothiocyanatomethyl)benzene according to step 1 general procedure. Yield (250 mg, 0.84 mmol) 47%.

[0266] 1H NMR (400 MHz, DMSO-d6) δ 3.82 (s, 3 H) 5.68 (s, 2 H) 7.20 - 7.25 (m, 1 H) 7.26 - 7.34 (m, 4 H) 7.36 - 7.42 (m, 3 H) 13.03 (s, 1 H); LC-MS: 97.93% at 2.73 min; m / z 299.0 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase- B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.81% at 9.47 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 57 and 58:Step 1: Synthesis of 7-bromo-3-(2-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 57)

[0267] Compound 57 was prepared from corresponding 2-amino-4-bromobenzoic acid and 1- chloro-2-isothiocyanatobenzene according to step 1 general procedure. (180 mg, 0.491 mmol) 21%.

[0268] 1H NMR (400 MHz, DMSO-d6) δ 7.45 - 7.50 (m, 3 H) 7.54 (dd, J=8.50, 1.77 Hz, 1 H) 7.60 - 7.65 (m, 2 H) 7.89 (d, J=8.44 Hz, 1 H) 13.22 (br s, 1 H); LC-MS: 99.62% at 2.77 min; m / z 366.8 [M-H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM NH4OACin water, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.69% at 11.25 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 2: Synthesis of 2-(allylthio)-7-bromo-3-(2-chlorophenyl) quinazolin-4(3H)-one (Compound 58)

[0269] Compound 58 was prepared from Compound 57 according to step 2 general procedure. (40 mg, 0.10 mmol) 24%

[0270] 1H NMR (400 MHz, DMSO-d6) δ 3.79 - 3.91 (m, 2 H) 5.13-5.14 (m, 1 H) 5.36 (dd, J=16.99, 1.47 Hz, 1 H) 5.86-5.94 (m, 1 H) 7.54 - 7.71 (m, 4 H) 7.74 (dd, J=7.89, 1.41 Hz, 1 H) 7.89 (d, J=1.83 Hz, 1 H) 8.01 (d, J=8.44 Hz, 1 H); LC-MS: 98.40% at 3.90 min; m / z 409.1 [M+2] [Column: X select CSH C18 (50X3.0 mm, 2.5 pm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.15% at 11.33 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phasc-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Watcr];Experimental details for Compounds 59 and 60:Compound 59 Compound 60Step 1: Synthesis of 7-bromo-3-(3-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 59)

[0271] Compound 59 was prepared from corresponding 2-amino-4-bromobenzoic acid and 1 - chloro-3-isothiocyanatobcnzcnc according to step 1 general procedure. Yield (230 mg, 0.63 mmol), 27%.

[0272] 1H NMR (400 MHz, DMSO-d6) δ 7.26 - 7.31 (m, 1 H) 7.44 - 7.54 (m, 4 H) 7.62 (d, J=1.47 Hz, 1 H) 7.86 (d, J=8.44 Hz, 1 H) 13.05 - 13.17 (m, 1 H); LC-MS: 97.07% at 2.834 min; m / z 366.8 [M-H] [Column: EVO C-18 (50X3.0 mm, 2.6 pm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 97.50% at 9.87 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 2: Synthesis of 2-(allylthio)-7-bromo-3-(3-chlorophenyl)quinazolin-4(3H)-one (Compound 60)

[0273] Compound 60 was prepared from Compound 59 according to the general procedure. Yield (45 mg, 0.10 mmol) 24%.

[0274] 1H NMR (400 MHz, DMSO-d6) δ ppm 3.84 (d, J=6.97 Hz, 2 H) 5.11 - 5.16 (m, 1 H) 5.35 (dd, J=16.99, 1.47 Hz, 1 H) 5.87-5.96 (m, 1 H) 7.48-7.49 (m, 1 H) 7.57 - 7.66 (m, 3 H) 7.70 (t, J=1.90 Hz, 1 H) 7.86 (d, J=1.83 Hz, 1 H) 7.99 (d, J=8.44 Hz, 1 H); LC-MS: 99.81% at 3.937 min; m / z 409.1 [M+2] [Column: X select CSH C18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.90% at 10.83 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 61:Synthesis of 3-benzyl-7-bromo-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 61)

[0275] Compound 61was prepared from corresponding 2-amino-4-bromobenzoic acid and (isothiocyanatomethyl)benzene according to step 1 general procedure. Yield (403 mg, 1.16 mmol) 83%.

[0276] 1H NMR (400 MHz, DMSO-d6) δ 5.64 (s, 2 H) 7.20 - 7.26 (m, 1 H) 7.27 - 7.34 (m, 4 H) 7.51 (dd, J=8.50, 1.77 Hz, 1 H) 7.59 (d, J=1.71 Hz, 1 H) 7.87 (d, J=8.44 Hz, 1 H) 13.08 (br s, 1 H); LC-MS: 94.77% at 3.309 min; m / z 349.0 [M+2] [Column: X select CSH C18 (50X3.0 mm,2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.54% at 10.51 min [Column: XSELECT CSH C18 (150 X 4.6 mm,3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1 .0 mL / min, Diluent: ACN:Water];Experimental details for Compounds 62, 63 & 64:Step 1: Synthesis of ethyl 2-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)acetate (Compound 62)

[0277] Compound 62 was prepared from corresponding 2-amino-4-bromobcnzoic acid and ethyl 2-isothiocyanatoacetate according to general procedure. Yield (323 mg, 0.94 mmol) 40% as white solid.

[0278] 1H NMR (400 MHz, DMSO-d6) δ 1.20 (t, J=7.15 Hz, 3 H) 4.16 (q, J=7.09 Hz, 2 H) 5.16 (s, 2 H) 7.55 (dd, J=8.44, 1.83 Hz, 1 H) 7.60 (d, J=1.59 Hz, 1 H) 7.90 (d, J=8.44 Hz, 1 H) 13.20 (s, 1 H); LC-MS: 97.76% at 2.789 min; m / z. 345.1 [M+2] [Column: X bridge BEH-C18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 95.67% at 7.33 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 2: Synthesis of ethyl 2-(2-(allylthio)-7-bromo-4-oxoquinazolin-3(4H)-yl)acetate (Compound 63)

[0279] Compound 63 was prepared from Compound 62 according to the general procedure. Yield (180 mg, 0.471 mmol) 57%.

[0280] 1H NMR (400 MHz, DMSO-d6) δ 1.21 (t, J=7.09 Hz, 3 H) 3.98 (d, J=6.85 Hz, 2 H) 4.18 (q, J=7.09 Hz, 2 H) 4.87 (s, 2 H) 5.19 (d, J=10.15 Hz, 1 H) 5.43 (dd, J=16.87, 1.34 Hz, 1 H) 5.92- 6.00 (m, 1 H) 7.65 (dd, J=8.50, 1.90 Hz, 1 H) 7.84 (d, J=1.71 Hz, 1 H) 7.99 (d, J=8.44 Hz, 1 H); LC-MS: 98.25% at 3.676 min; m / z 385.0 [M+2] [Column: X select CSH C18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 96.31% at 10.02 min [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 3: Synthesis of 2-(2-(allylthio)-7-bromo-4-oxoquinazolin-3(4H)-yl)acetic acid (Compound 64)

[0281] Compound 64 was prepared from Compound 63 according to the general procedure. Yield (50 mg, 0.141 mmol) 35% as white solid.

[0282] 1H NMR (400 MHz, DMSO-d6) δ 3.98 (d, J=6.85 Hz, 2 H) 4.77 (s, 2 H) 5.16 - 5.21 (m, 1 H) 5.43 (dd, J=16.99, 1.59 Hz, 1 H) 5.92-6.01 (m, 1 H) 7.64 (dd, J=8.50, 1.90 Hz, 1 H) 7.83 (d, J=1.83 Hz, 1 H) 7.99 (d, J=8.44 Hz, 1 H) 13.39 - 13.51 (m, 1 H); LC-MS: 95.92% at 2.852 min; m / z 354.8 [M-H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 96.46% at 10.46 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 65:Step 1: Synthesis of methyl 4-bromo-5-methoxy-2-nitrobenzoate

[0283] To a solution of methyl 4-bromo-5-fluoro-2-nitrobenzoate (20 g, 72.2 mmol) in methanol (200 mL) was added sodium methoxide (1.5 eq) at 0°C and the resulting reaction mixture was stirred at rt for 1 h. Progress of the reaction was monitored by TLC. After completion of starting material, reaction mixture was cooled to room temperature, the Reaction mixture was poured in ice cold water. The precipitated solid was filtered and residue was washed with water to afford methyl 4-bromo-5-methoxy-2-nitrobenzoate (19 g, 66 mmol) 91% as white solid.

[0284] 1H NMR (400 MHz, DMSO-d6) δ 3.87 (s, 3 H) 4.03 (s, 1 H) 7.46 (s, 1 H) 8.41 (s, 1 H);Step 2: Synthesis of methyl 2-amino-4-bromo-5-methoxybenzoate

[0285] To a solution of methyl 4-bromo-5-methoxy-2-nitrobenzoate (5 g, 17.2 mmol) in methanol and water was added iron (5 eq) and ammonium chloride (10 eq) at rt and the reaction mixture was stirred at 60°C for 4h. After completion reaction mixture was cooled to RT and filteredthrough celite bed and washed with Ethyl acetate. Filtrate was washed with water and concentrated to afford pale brown liquid which was triturated with hexane afforded methyl 2-amino-4-bromo- 5-methoxybenzoate (2.9 g, 11.1 mmol) 65% as pale yellow solid.

[0286] 1H NMR (500 MHz, DMSO-d6) δ 3.79 (s, 3 H) 3.72 (s, 1 H) 6.42 (brs, 2H) 7.12 (s, 1 H) 7.23 (s, 1 H); LC-MS: 88.21 at 2.733 min; m / z 260 [M+H] [Column: X bridge BEH-C18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]Step 3: Synthesis of 7-bromo-6-methoxy-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)- one

[0287] 7-bromo-6-methoxy-3-phenyl-2-thioxo-2,3-dihydroquinazolin-4(lH)-one was prepared from corresponding methyl 2-amino-4-bromo-5-methoxybenzoate and isothiocyanatobenzene according to step 1 general procedure. Yield (95 mg, 0.262 mmol) 34% as white solid.

[0288] 1H NMR (400 MHz, DMSO-d6) δ 3.92 (s, 3 H) 7.24 - 7.29 (m, 2 H) 7.37 - 7.50 (m, 4 H) 7.71 (s, 1 H) 13.01 (s, 1 H); LC-MS: 97.02% at 2.60 min; m / z 362.8 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 98.31% at 9.00 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 4: Synthesis of 2-(allylthio)-7-bromo-6-methoxy-3-phenylquinazolin-4(3H)-one (Compound 65)

[0289] Compound 65 was prepared from 7-bromo-6-methoxy-3-phenyl-2-thioxo-2,3- dihydroquinazolin-4(lH)-one according to step 2 general procedure. Yield (60 mg, 0.136 mmol) 71%.

[0290] 1H NMR (500 MHz, DMSO-d6) δ 3.79 (d, J=7.14 Hz, 2 H) 3.95 (s, 3 H) 5.11 (d, J=10.11 Hz, 1 H) 5.33 (dd, J=16.95, 1.19 Hz, 1 H) 5.86-5.93 (m, 1 H) 7.42 - 7.46 (m, 2 H) 7.52 - 7.58 (m, 4 H) 7.94 (s, 1 H); LC-MS: 91.39% at 3.681 min; m / z 403.1 [M+H] [Column: X bridge BEH-C18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 98.80% at 8.678 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% Ammonia in 2.5 mM Ammonium Bicarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compounds 66 and 67:Step 1: Synthesis of 7-bromo-3-(2-chlorophenyl)-6-methoxy-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (Compound 66)

[0291] Compound 66 was prepared from corresponding methyl 2-amino-4-bromo-5- methoxybenzoate and l-chloro-2-isothiocyanatobenzene according to step 1 general procedure. (173 mg, 0.48 mmol) 24%.

[0292] 1H NMR (500 MHz, DMSO-d6) δ 3.94 (s, 3 H) 7.45 - 7.51 (m, 4 H) 7.62 (br s, 1 H) 7.73 (s, 1 H) 13.16 (hr s, 1 H); LC-MS: 99.55% at 2.872 min; m7z 397.0 [M+H] [Column: X bridge BEH-C18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase- B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.63% at 9.60 min [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 4: Synthesis of 2-(allylthio)-7-bromo-3-(2-chlorophenyl)-6-methoxyquinazolin-4(3H)- one (Compound 67)

[0293] Compound 67 was prepared from Compound 66 according to step 2 general procedure. (80 mg, 0.20 mmol) 60%

[0294] 1H NMR (500 MHz, DMSO-d6) δ 3.75 - 3.87 (m, 2 H) 3.96 (s, 3 H) 5.12 (br d, J=9.81 Hz, 1 H) 5.33 (br d, J= 16.95 Hz, 1 H) 5.83 - 5.94 (m, 1 H) 7.53 - 7.63 (m, 3 H) 7.66 (br d, J=7.73 Hz, 1 H) 7.73 (d, J=7.44 Hz, 1 H) 7.95 (s, 1 H); LC-MS: 98.77% at 3.493 min; m / z 438.8 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase- B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.12% at 4.461 min [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ), Mobile Phase-A: 0.05% Ammonia in 2.5 mM Ammonium Bicarbonate, Mobile Phase-B: ACN, Flow: 1.5 mL / min, Diluent: ACN:Water].Experimental details for Compound 68:Step 1: Synthesis of 7-bromo-3-(3-chlorophenyl)-6-methoxy-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (Compound 68)

[0295] Compound 68 was prepared from corresponding methyl 2-amino-4-bromo-5- methoxybenzoate and l-chloro-3-isothiocyanatobenzene according to step 1 general procedure. Yield (80 mg, 0.32 mmol), 19%.

[0296] 1H NMR (400 MHz, DMSO-d6) δ 3.92 (s, 3 H) 7.27-7.29 (m, 1 H) 7.41 - 7.54 (m, 4 H) 7.70 (s, 1 H) 13.05 (s, 1 H); LC-MS: 99.19% at 2.815 min; m / z 396.8 [M-H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 97.62% at 9.80 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 69:Synthesis of 3-benzyl-7-bromo-6-methoxy-2-thioxo-2,3-dihydroquinazolin-4(lH)-one(Compound 69)

[0297] Compound 69 was prepared from corresponding methyl 2-amino-4-bromo-5- methoxybenzoate and (isothiocyanatomethyl)benzene according to the general procedure. Yield (160 mg, 0.425 mmol) 55% as white solid.

[0298] 1H NMR (500 MHz, DMSO-d6) δ 3.92 (s, 3 H) 5.67 (s, 2 H) 7.21 - 7.35 (m, 5 H) 7.45 (s, 1 H) 7.68 (s, 1 H) 13.03 (s, 1 H); LC-MS: 96.24% at 2.949 min; m / z 378.8 [M+H] [Column: DIRECT_MASS_3.M, Mobile Phase-B: 0.025% Formic acid, Flow Rate: 0.5 mL / min (Run time:0.6min)]; HPLC: 99.88% at 10.47 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compounds 70:Synthesis of ethyl 2-(7-bromo-6-methoxy-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)- yl)acetate (Compound 70)

[0299] Compound 70 was prepared from corresponding methyl 2-amino-4-bromo-5- methoxybenzoate and ethyl 2-isothiocyanatoacetate according to the general procedure. Yield (155 mg, 0.416 mmol) 55% white solid.

[0300] 1H NMR (500 MHz, DMSO-d6) δ 1.21 (t, J=6.99 Hz, 3 H) 3.94 (s, 3 H) 4.15 (q, J=7.04 Hz, 2 H) 5.18 (s, 2 H) 7.47 (s, 1 H) 7.69 (s, 1 H) 13.14 (s, 1 H); LC-MS: 97.66% at 2.81 min; m7z 373.0 [M+H] [Column: X bridge BEH-C18 (50X3.0 mm, 2.5 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.79% at 9.30 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 71, 72 and 73:Step 1: Synthesis of methyl 3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazoline-6-carboxylate

[0301] dimethyl 4-aminoisophthalate (250 mg, 1.196 mmol) was dissolved in pyridine and to this was added l-chloro-2-isothiocyanatobenzene (241 mg, 1.43mmol), resulting mixture was stirred for 16 h at 80 °C. After completion, reaction mixture was concentrated and triturated with DCM and pentane twice afforded methyl 3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazoline-6-carboxylate (200 mg, 0.578 mmol) 48% as white solid.

[0302] 1H NMR (400 MHz, DMSO-d6) δ 3.89 (s, 3 H) 7.45 - 7.57 (m, 4 H) 7.60 - 7.67 (m, 1 H) 8.32 (dd, J=8.62, 2.02 Hz, 1 H) 8.48 (d, J=1.96 Hz, 1 H) 13.47 (s, 1 H); LC-MS: 96.32% at 2.63 min; m / z 347.1 [M+H] [Column: Evo-C18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 98.19% at 10.37 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water],Step 2: Synthesis of methyl 2-(alIylthio)-3-(2-chlorophenyl)-4-oxo-3,4-dihydroquinazoline-6- carboxylate (Compound 71)

[0303] Compound 71 was prepared from methyl 3-(2-chlorophenyl)-4-oxo-2-thioxo-l,2,3,4- tetrahydroquinazoline-6-carboxylate according to step 2 general procedure. Yield (60 mg, 0.147 mmol) 38% as off white solid.

[0304] 1H NMR (400 MHz, DMSO-d6) δ 3.81 - 3.97 (m, 5 H) 5.10 - 5.19 (m, 1 H) 5.31 - 5.42 (m, 1 H) 5.88-5.96 (m, 1 H) 7.55 - 7.67 (m, 2 H) 7.69 - 7.78 (m, 3 H) 8.35 (dd, J=8.5O, 2.14 Hz, 1 H) 8.64 (d, J=1.71 Hz, 1 H); LC-MS: 96.94% at 3.35 min; m / z 387.1 [M+H] [Column: Evo-C18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 98.87% at 11.7 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 3: Synthesis of 2-(allylthio)-3-(2-chlorophenyl)-4-oxo-3,4-dihydroquinazoline-6- carboxylic acid (Compound 72)

[0305] Compound 72 was prepared from Compound 71 according to the general procedure. Yield (70 mg, 0.188 mmol) 52% as off white solid.

[0306] 1H NMR (400 MHz, DMSO-d6) δ 3.84-3.93 (m, 2 H) 5.15 (d, J=10.64 Hz, 1 H) 5.36(dd, J=16.99, 1.34 Hz, 1 H) 5.89-5.96 (m, 1 H) 7.55 - 7.66 (m, 2 H) 7.69 - 7.78 (m, 3 H) 8.33 (dd, J=8.50, 2.02 Hz, 1 H) 8.62 (d, J=1.83 Hz, 1 H) 13.23 - 13.37 (m, 1 H); LC-MS: 97.17% at 2.84min; m / z 373.0 [M+H] [Column: Evo-C18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.29% at 10.4 min [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Step 4: Synthesis of 2-(allylthio)-3-(2-chlorophenyl)-4-oxo-3,4-dihydroquinazoline-6- carboxamide (Compound 73)

[0307] Compound 72 (80 mg, 0.897 mmol) was dissolved in DMF (4 mL) and to this mixture was added NH4CI (2.5 eq), EDC.HCl (1.5 eq) and DMAP (3 eq) at 0 °C and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of starting material, reaction mixture was diluted with water (40 mL). The formed solid was filtered and solid was washed with water and dried to afford compound 73 (18 mg, 0.07 mmol) 23% as off white solid.

[0308] 1H NMR (400 MHz, DMSO-d6) δ 3.84-3.92 (m, 2 H) 5.14 (d, J=9.90 Hz, 1 H) 5.36 (dd, J=16.99, 1.22 Hz, 1 H) 5.88-5.96 (m, 1 H) 7.50 (br s, 1 H) 7.55 - 7.66 (m, 2 H) 7.68 - 7.77 (m, 3 H) 8.26 (br s, 1 H) 8.31 (dd, J=8.5O, 2.02 Hz, 1 H) 8.63 (d, J=1.96 Hz, 1 H); LC-MS: 94.00% at 2.58 min; m / z 372.0 [M+H] [Column: Evo-C18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 97.34% at 8.93 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compounds 74-77:Step 1: Synthesis of methyl 3-(3-chlorophenyl)-4-oxo-2-thioxo-l,2,3,4- tetrahydroquinazoline-6-carboxylate (Compound 74)

[0309] Compound 74 was prepared from corresponding dimethyl 4-aminoisophthalate and 1- chloro-3-isothiocyanatobenzene according to general procedure. Yield (210 mg, 0.606 mmol) 87% as white solid.

[0310] 1H NMR (500 MHz, DMSO-d6) δ 3.89 (s, 3 H) 7.31-7.33 (m, 1 H) 7.47 - 7.56 (m, 4 H) 8.29 (dd, J=8.63, 1.78 Hz, 1 H) 8.46 (d, J=2.08 Hz, 1 H) 13.35 (s, 1 H); LC-MS: 97.07% at 2.65 min; m / z 348.9 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 96.60% at 9.17 min [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ), Mobile Phase-A: 0.05% TFA in water:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA in water (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Step 2: Synthesis of methyl 2-(allylthio)-3-(3-chlorophenyl)-4-oxo-3,4-dihydroquinazoline-6- carboxylate (Compound 75)

[0311] Compound 75 was prepared from Compound 74 according to the general procedure. Yield (140 mg, 0.36 mmol) 60% yield as white solid.

[0312] 1H NMR (500 MHz, DMSO-d6) δ 3.87 (d, J=7.14 Hz, 2 H) 3.91 (s, 3 H) 5.15 (d, J=10.11 Hz, 1 H) 5.36 (dd, J=16.95, 1.19 Hz, 1 H) 5.90-5.96 (m, 1 H) 7.52 (br d, J=7.73 Hz, 1 H) 7.59 - 7.68 (m, 2 H) 7.73 (dd, J=4.91, 3.42 Hz, 2 H) 8.32 (dd, J=8.48, 1.93 Hz, 1 H) 8.62 (d, J=1.78 Hz, 1 H); LC-MS: 96.33% at 3.53 min; m / z 387.1 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium formate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 96.57% at 9.68 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 3: Synthesis of 2-(allylthio)-3-(3-chlorophenyl)-4-oxo-3,4-dihydroquinazoline-6- carboxylic acid (Compound 76)

[0313] Compound 76 was prepared from Compound 75 according to the general procedure. Yield (60 mg, 0.16 mmol) 70% as white solid.

[0314] 1H NMR (400 MHz, DMSO-d6) δ 3.87 (d, J=6.97 Hz, 2 H) 5.12 - 5.17 (m, 1 H) 5.36 (dd, J=16.99, 1.47 Hz, 1 H) 5.89-5.97 (m, 1 H) 7.49-7.51 (m, 1 H) 7.58 - 7.67 (m, 2 H) 7.68 - 7.73 (m, 2 H) 8.30 (dd, J=8.56, 2.08 Hz, 1 H) 8.61 (d, J=1.71 Hz, 1 H) 13.26 (br s, 1 H); LC-MS: 96.33% at 2.14 min; m / z 373.1 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase- A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)];HPLC: 96.75% at 10.62 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];

[0315] Step 4: Synthesis of 2-(allylthio)-3-(3-chlorophenyl)-4-oxo-3,4-dihydroquinazoline-6- carboxamide (Compound 77)

[0316] Compound 77 was prepared from Compound 76 according to the general procedure. Yield (30 mg, 0.08 mmol) 60% as white solid.

[0317] 1H NMR (400 MHz, DMSO-d6) δ 3.86 (d, J-6.85 Hz, 2 H) 5.14 (d, J=9.90 Hz, 1 H) 5.35 (dd, J=16.93, 1.28 Hz, 1 H) 5.89-5.97 (m, 1 H) 7.50 (br dd, J=7.58, 1.59 Hz, 2 H) 7.57 - 7.74 (m, 4 H) 8.22 - 8.33 (m, 2 H) 8.62 (d, J=1.83 Hz, 1 H); LC-MS: 96.75% at 2.65 min; m / z 372.9 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 98.56% at 9.17 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phasc-B: ACN:0.05% TFA (95:05), Flow: 1.0 mE / min, Diluent: ACN:Watcr];Experimental details for Compounds 78 and 79:Step 1: Synthesis of methyl 3-benzyl-4-oxo-2-thioxo-l,2,3,4-tetrahydroquinazoline-6- carboxylate

[0318] Methyl 3-benzyl-4-oxo-2-thioxo-l,2,3,4-tetrahydroquinazoline-6-carboxylate was prepared from corresponding dimethyl 4-aminoisophthalate and (isothiocyanatomethyl)benzene according to step 1 general procedure. Yield (235 mg, 0.720 mmol) 50% yield as white solid.

[0319] 1H NMR (500 MHz, DMSO-d6) δ 3.88 (s, 3 H) 5.66 (s, 2 H) 7.21 - 7.36 (m, 5 H) 7.49 (d, J=8.63 Hz, 1 H) 8.26 (dd, J=8.63, 1.78 Hz, 1 H) 8.48 (d, J=1 .78 Hz, 1 H) 13.31 (s, 1 H); LC- MS: 96.50% at 2.84 min; m / z 327.1 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), MobilePhase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 96.20% at 9.64 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Step 2: Synthesis of methyl 2-(alIylthio)-3-benzyl-4-oxo-3,4-dihydroquinazoline-6- carboxylate

[0320] Methyl 2-(allylthio)-3-benzyl-4-oxo-3,4-dihydroquinazoline-6-carboxylate was prepared from methyl 3-benzyl-4-oxo-2-thioxo-l,2,3,4-tetrahydroquinazoline-6-carboxylate according to the general procedure. Yield (205 mg, 0.56 mmol) 83% yield as off white solid.

[0321] 1H NMR (400 MHz, DMSO-d6) δ 3.91 (s, 3 H) 3.96 (d, J=6.97 Hz, 2 H) 5.16 (d, J=10.03 Hz, 1 H) 5.32 - 5.41 (m, 3 H) 5.91-5.99 (m, 1 H) 7.24 - 7.36 (m, 5 H) 7.69 (d, J=8.56 Hz, 1 H) 8.29 (dd, J=8.56, 1.96 Hz, 1 H) 8.66 (d, J=1.96 Hz, 1 H); LC-MS: 93.51% at 3.34 min; rn / z 367.0 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phasc-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 95.90% at 10.31 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step 3: Synthesis of 2-(allylthio)-3-benzyl-4-oxo-3,4-dihydroquinazoline-6-carboxylic acid (Compound 78)

[0322] Compound 78 was prepared from methyl 2-(allylthio)-3-benzyl-4-oxo-3,4- dihydroquinazoline-6-carboxylate according to step 5 general procedure. Yield (90 mg, 0.225 mmol) 74% as off white solid.

[0323] 1H NMR (500 MHz, DMSO-d6) δ 3.96 (d, J=6.84 Hz, 2 H) 5.16 (d, J=9.81 Hz, 1 H) 5.31 - 5.42 (m, 3 H) 5.93-5.96 (m, 1 H) 7.23 - 7.30 (m, 3 H) 7.31 - 7.36 (m, 2 H) 7.67 (d, J=8.63 Hz, 1 H) 8.28 (dd, J=8.63, 1.78 Hz, 1 H) 8.66 (d, J=L78 Hz, 1 H) 13.27 (br s, 1 H); LC-MS: 94.97% at 2.06 min; m / z 353.2 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase- A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 95.09% at 8.63 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase- A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];Step 4: Synthesis of 2-(allylthio)-3-benzyl-4-oxo-3,4-dihydroquinazoline-6-carboxamide (Compound 79)

[0324] Compound 79 was prepared from compound 78 according to the general procedure to yield (150 mg, 0.427 mmol) 81% as white solid.

[0325] 1H NMR (400 MHz, DMSO-d6) δ 3.96 (d, J=6.97 Hz, 2 H) 5.14-5.14 (m, 1 H) 5.33 - 5.41 (m, 3 H) 5.91-5.99 (m, 1 H) 7.21 - 7.38 (m, 5 H) 7.48 (br s, 1 H) 7.64 (d, J=8.56 Hz, 1 H) 8.20 - 8.30 (m, 2 H) 8.66 (d, J=1.96 Hz, 1 H); LC-MS: 99.01% at 2.68 min; m / z 352.2 [M+H] [Column: EVO C-18 (50X3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow Rate: 0.8 mL / min (Gradient)]; HPLC: 99.72% at 9.02 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 80Synthesis of 7-bromo-3-(2-methoxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 80)

[0326] Compound 80 was prepared from corresponding 2-amino-4-bromobenzoic acid and 1- isothiocyanato-2-methoxybenzene according to the general procedure. Off white solid (650 mg, 1.79 mmol) 77%.

[0327] LC-MS: 98.82% at 2.62 min; m / z 361.1 [M-H] [Column:Kinetex EVO-C 18(3.0X50 mm, 2.6 μm). Mobile Phase-A: 0.025%Formic acid, Mobile Phase-B: ACNT / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)] ; HPLC: 98.08% at 9.11 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA: ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program: T / B%: 0.01 / 10,8 / 80,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (500 MHz, DMSO-d6) δ = 13.06 (br s, 1H), 7.87 - 7.85 (m, 1H), 7.62 (d, J= 1.9 Hz, 1H), 7.52 (dd, J= 1.3, 8.3 Hz, 1H), 7.43 - 7.39 (m, 1H), 7.22 (dd, J = 1.3, 7.7 Hz, 1H), 7.15 (d, J= 7.7 Hz, 1H), 7.04 (t, J= 7.4 Hz, 1H), 3.71 (s, 3H)Experimental details for Compound 81Synthesis of 7-bromo-3-(2-hydroxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 81)

[0328] To a solution of Compound 80 (300 mg, 0.83 mmol) in DCM (6 mL) was added BBrs (IM DCM) (1.66 mL, 1.66 mmol) at 0°C and the reaction mixture was stirred at RT for 16h. Progress of reaction was monitored by TLC. After completion, the reaction mixture was quenched with methanol (2 mL) and diluted with DCM (40 mL) and washed with water (3 x 30 mL). The organic layer was separated, dried over anhydrous Na2SO4and concentrated in vacuo. The crude was purified by Combi flash chromatography (using 30% EtOAc in hexane) and reverse phase purification to afford Compound 81 (30 mg, 0.057 mmol) as white solid.10%.

[0329] LC-MS: 98.65% at 2.34 min; m / z 349.1 and 351.1 [M+H, M+H+2] [Column:Kinetex EVO-C 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)]; HPLC: 98.88% at 8.01 min; [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program: T / B%: 0.01 / 10,8 / 80,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 13.01 (s, 1H), 9.54 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 1.7 Hz, 1H), 7.51 (dd, J = 1.8, 8.4 Hz, 1H), 7.25 - 7.18 (m, 1H), 7.10 (dd, J = 1.5, 7.8 Hz, 1H), 6.90 (dd, 7 = 1.0, 8.1 Hz, 1H), 6.88 - 6.83 (m, 1H)Experimental details for Compound 82:Step 1: Synthesis of methyl 2-amino-4-bromobenzoate

[0330] To a stirred solution of 2-amino-4-bromobenzoic acid (3 g, 13.8 mmol) in methanol (30mL) was added H2SO4(4.4 mL, 83.2 mol) at 0°C and the resulting reaction mixtue was stirredfor 16h at 60°C, The progress of the reaction was monitored by TLC. After 16 h methanol was concentrated and resulting residue was diluted with water to affod solid which was filtred and dried to afford methyl 2-amino-4-bromobenzoate (3g, 13.04 mmol) 93% as off white solid.Step 2: Synthesis of methyl 4-bromo-2-isothiocyanatobenzoate

[0331] To a stirred solution of methyl 2-amino-4-bromobenzoate (1 g, 4.34 mmol) in THF(20 mL) was added Et3N(2.47 mL, 17.7 mmol) and thiophosgene(600 mg, 5.21 mmol) at 0 °C and resulatant reaction mixture was stirerd for 16 h at rt. After completion of the reaction as indicated by TLC, reaction mixture was diluted with ethylacetate and washed with water, organic layer was dried over anhydrous Na2SO4and concentrated to crude product which was purified by flash column chromatogray using 3-8% EtOAc in hexane as eluent to afford methyl 4-bromo-2- isothiocyanatobenzoate (700 mg, 2.57 mmol) 59% as pale brown solid.1H NMR (400 MHz, DMSO-d6) δ = 7.97 - 7.81 (m, 2H), 7.71 (dd, J = 2.0, 8.6 Hz, 1H), 3.88 (s, 3H).Step 3: Synthesis of 7-bromo-3-(2-(dimethylamino)phenyl)-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one (Compound 82)

[0332] Compound 82 was prepared from corresponding methyl 4-bromo-2- isothiocyanatobenzoate and N1,N1-dimethylbenzene-l,2-diamine according to the general procedure. (160 mg, 0.43 mmol) 58% pale brown solid.

[0333] LC-MS: 97.45% at 2.16 min; m / z 376.0 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase- A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate; 0.8 mL / min( Gradient)] HPLC: 99.00% at 6.07 min. [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B% : 0.01 / 10,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 13.07 (s, 1H), 7.88 (d, J = 8.6 Hz, 1H), 7.63 (d, J = 1.7 Hz, 1H), 7.51 (dd, 7 = 1.8, 8.4 Hz, 1H), 7.38 - 7.32 (m, 1H), 7.23 - 7.15 (m, 2H), 7.07 (m, 1H), 2.56 (s, 6H)Experimental details for Compound 83:Synthesis of 2-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)- yl)benzenesulfonamide (Compound 83)

[0334] Compound 83 was prepared from corresponding 2-aminobenzenesulfonamide and methyl 4-bromo-2-isothiocyanatobenzoate (common intermediate) according to the general procedure. Compound 83 as a pale brown solid (60 mg, 0.14 mmol) 19%.

[0335] LC-MS: 96.10% at 2.25 min; 412.0 [M+H]+; [Column:EVO C-18(3.OX5O mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate; 0.8 mL / min(Gradient)] ; HPLC: 98.59% at 8.66 min; [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B% : 0.01 / 10,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Watcr|;1H NMR (400 MHz, DMSO-d6) δ = 13.07 (s, 1H), 8.00 (dd, J = 1.3, 7.8 Hz, 1H), 7.85 (m, 1H), 7.74 - 7.58 (m, 3H), 7.52 (dd, 7 = 1.7, 8.6 Hz, 1H), 7.45 (m, 1H), 7.22 (s, 2H)Experimental details for Compounds 84, 85 and 86:Step 1: Synthesis of 3-(2-aminophenyl)-7-bromo-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 84)

[0336] Compound 84 was prepared from corresponding benzene- 1 ,2-diamine and methyl 4- bromo-2-isothiocyanatobenzoate (common intermediate) according to the general procedure. Brown solid (1.8 g, 5.17 mmol) Yield: 70%.

[0337] LC-MS: 99.82% at 2.34 min; m / z 348.0 [M+H]+[Column:EVO C-18(3.OX5O mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)] ; HPLC: 99.79% at 8.85 min; [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B% : 0.01 / 10,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 12.87 (s, 1H), 7.83 (d, J = 8.4 Hz, lH), 7.59 (d, J= 1.7 Hz, 1H), 7.47 (dd, J = 1.7, 8.4 Hz, 1H), 7.06 - 7.02 (m, 1H), 6.86 (dd, J = 1.3, 7.7 Hz, 1H), 6.69 (d, J = 8.1 Hz, 1H), 6.53 (t, J = 7.5 Hz, 1H), 5.16 (br s, 2H)Step 2: Synthesis of DiBoc derivative of 3-(2-aminophenyl)-7-bromo-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (Compound 85)

[0338] To a stirred solution of compound 84 (1g, 2.82 mmol) and tricthylaminc (1 mL, 7.15 mmol) in Toluene (20 mL) was added Iodine (871 mg, 3.43 mmol), N,N-di-Boc-thiourea (950 mg, 3.44 mmol) at 0°C, reaction was stirred at RT for 16 h. Progress of the reaction was monitored by TLC. Reaction was diluted with water and extracted with EtOAc, combined organic layers were washed with water and dried over Na2SO4, concentrated. Crude compound was purified by Normal phase Combi flash chromatography to afford Compound 85 (600 mg, 1.02 mmol) 35% yield as off white solid.

[0339] LC-MS: 97.30% at 3.49 min; m / z 590.1 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]; HPLC: 97.14% at 10.23 min; [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,5 / 80,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 13.29 (s, 1H), 11.29 (s, 1H), 10.31 (s, 1H), 8.28 (d, J= 8.2 Hz, 1H), 7.87 (d, J= 8.4 Hz, 1H), 7.65 (s, 1H), 7.54 - 7.46 (m, 2H), 7.38 (d, J = 7.8 Hz, 1H), 7.30 - 7.23 (m, 1H), 1.42 (s, 9H), 1.19 (s, 9H)Step-3: synthesis of l-(2-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)- yl)phenyl)guanidine (Comound 86)

[0340] To a stirred solution of Compound 85 (500 mg, 0.85 mmol) in DCM (10 mL) was added TFA (1 mL, 15 mmol), at 0°C, resulting reaction was stirred at RT for 16 h. progress of the reaction was monitored by TLC. After completion of reaction solvent was evaporated under reduced pressure obtained solid was triturated with Et2O, dried under vacuum to afford Comound 86 (287 mg, 0.74 mmol) 87% as white solid.

[0341] LC-MS: 95.98% at 1.44 min; m / z 390.2, 392.2 [M+H]+and [M+2+H] ;[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)] ; HPLC: 98.75% at 5.59 min; [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5iμ) Mobile Phase-A: 5 mM Ammonium Bicarbonate; Mobile Phase-B: ACN Program T / B%: 0.01 / 20,12 / 90,16 / 90. Flow: 1 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 13.22 (br s, 1H), 9.03 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 1.5 Hz, 1H), 7.59 - 7.50 (m, 2H), 7.50 - 7.42 (m, 3H), 7.26 (br s, 3H)Experimental details for Compound 87:Synthesis of 3-(2-chlorophenyl)-7-fluoro-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 87)

[0342] Compound 87 was prepared from corresponding 2-amino-4-fluorobenzoic acid and 1- chloro-2-isothiocyanatobenzene according to the general procedure. White solid (70 mg, 0.22 mmol) 12%.

[0343] LC-MS: 98.62 % at 2.58 min; m / z 306.9 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate; 0.8 mL / min(Gradient)] ; HPLC: 97.43% at 8.98 min; [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,8 / 80,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 13.25 (br s, 1H), 8.05 (dd, J = 6.1, 8.7 Hz, 1H), 7.66 - 7.57 (m, 1H), 7.52 - 7.43 (m, 3H), 7.28 - 7.15 (m, 2H)Experimental details for Compound 88:Synthesis of 7-chloro-3-(2-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 88)

[0344] Compound 88 was prepared from corresponding 2-amino-4-chlorobenzoic acid and 1- chloro-2-isothiocyanatobenzene according to the general procedure. White solid (20 mg, 0.06 mmol) 4%.

[0345] LC-MS: 99.59% at 2.75 min; m / z 322.9 [M+H]+; [Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]; HPLC: 99.50% at 9.55 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,8 / 80,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (500 MHz, DMSO-d6) δ = 13.23 (br s, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.63 - 7.59 (m, 1H), 7.49 - 7.46 (m, 4H), 7.40 (dd, 7 = 1.3, 8.3 Hz, 1H)Experimental details for Compound 89:Synthesis of 3-(2-chlorophenyl)-2-thioxo-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(lH)- one (Compound 89)

[0346] Compound 89 was prepared from corresponding 2-amino-4-(trifluoromethyl)benzoic acid and l-chloro-2-isothiocyanatobenzene according to the general procedure White solid (282 mg, 0.79 mmol) 54%.

[0347] LC-MS: 98.98% at 2.84 min; m / z 356.9 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 2.5 mM NH4OAC in water, Mobile Phase-B: ACN T / B%:0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5; Flow rate: 0.8 mL / min(Gradient)]; HPLC: 97.30% at 10.23 min. [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,8 / 80,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (500 MHz, DMSO-d6) δ = 13.42 (br s, IH), 8.19 (d, J = 8.3 Hz, IH), 7.76 (s, IH), 7.70 - 7.67 (m, IH), 7.65 - 7.63 (m, IH), 7.52 - 7.48 (m, 3H)Experimental details for Compound 90Step-1: Synthesis of tert-butyl 4-(4-methylpiperazin-l-yl)-2-nitrobenzoate

[0348] N-mcthylpipcrazinc(2.87g, 28.6 mmol) was added to tcrt-butyl 4-fluoro-2- nitrobenzoate (2g, 8.29 mmol) and the reaction mixture was stirred for 16h at room temperature. The progress of the reaction was monitored by TLC. After completion, reaction mixture was diluted with water and stirred for Ih. The formed solid was filtered and dried to afford tert-butyl 4-(4-methylpiperazin-l-yl)-2-nitrobenzoate (2 g, 6.2 mmol) as off white solid. Yield: 75%.

[0349] LC-MS: 99.87% at 1.59 min; m / z 322.2 [M+H]+[Column:EVO C- 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]1H NMR (400 MHz, DMSO-d6) 8 = 7.67 (d, J = 8.9 Hz, IH), 7.28 (d, J = 2.2 Hz, IH), 7.13 (dd, J= 2.3, 8.9 Hz, IH), 3.39 - 3.34 (m, 4H), 2.46 - 2.36 (m, 4H), 2.21 (s, 3H), 1.44 (s, 9H)Step-2: Synthesis of tert-butyl 2-amino-4-(4-methylpiperazin-l-yl)benzoate

[0350] To a solution of tert-butyl 4-(4-methylpiperazin-l-yl)-2-nitrobenzoate (2 g, 6.22 mmol) in methanol (20 mL) and water(lOmL) was added iron (1.73 g, 31 mmol) and ammonium chloride (3.32 g, 62 mmol) at rt and the reaction mixture was stirred at 60°C for 4h. After completion reaction mixture was cooled to rt and filtered through celite bed and washed with ethyl acetate.Filtrate was washed with water and concentrated to afford pale brown liquid which was triturated with hexane afforded tert-butyl 2-amino-4-(4-methylpiperazin-l-yl)benzoate (1.75 g, 6.01 mmol) as off white solid. Yield:96%.

[0351] LC-MS: 99.65% at 1.53 min; m / z 292.3 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5; Flow rate: 0.8 mL / min(Gradient)].1H NMR (400 MHz, DMSO-d6) δ = 7.47 (d, J = 9.0 Hz, 1H), 6.40 (br s, 2H), 6.18 (br dd, J = 2.1, 9.0 Hz, 1H), 6.14 - 6.09 (m, 1H), 3.23 - 3.09 (m, 4H), 2.42 - 2.34 (m, 4H), 2.20 (s, 3H), 1.49 (s, 9H);Step-3: Synthesis of 2-amino-4-(4-methylpiperazin-l-yl)benzoic acid .trifluoroacetic acid salt

[0352] To a stirred solution of tert-butyl 2-amino-4-(4-methylpiperazin-l-yl)benzoate (1.75 g, 6 mmol) in DCM (50 mL) was added TFA (4.7 mL, 60 mmol), at 0°C, resulting reaction was stirred at RT for 16 h. progress of the reaction was monitored by TLC. After completion of reaction, reaction mixture was concentrated and the residue was triturated with diethylether to afford 2-amino-4-(4-mcthylpipcrazin-l-yl)bcnzoic acid .trifluoroacctic acid salt (1.8 g, 5.42 mmol) as off white solid. Yield: 90%.

[0353] LC-MS: 96.96% at 0.315 min: m / z 236 [M+H]+, [Column:EVO C- 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)]1H NMR (400 MHz, DMSO- d6) δ = 9.92 - 9.79 (m, 1H), 7.56 (d, J= 8.9 Hz, 1H), 6.28 - 6.15 (m, 2H), 4.00 - 3.70 (m, 2H), 3.59 - 3.36 (m, 4H), 3.24 - 2.96 (m, 4H), 2.84 (s, 3H)Step-4: Synthesis of 3-(2-chlorophenyl)-7-(4-methylpiperazin-l-yl)-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (Compound 90)

[0354] Compound 90 was prepared from corresponding 2-amino-4-(4-methylpiperazin-l- yl)benzoic acid .trifluoroacetic acid salt and l-chloro-2-isothiocyanatobenzene according to the general procedure. Compound 90 was purified by recrystallization from EtOAc. Off white solid. (200 mg, 0.518 mmol) 34%.

[0355] LC-MS: 97.89% at 1.47 min; m / z 387.1 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]; HPLC: 98.95% at 5.67 min; [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,12 / 90,16 / 90. Flow: 1.0mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 12.94 - 12.59 (m, 1H), 7.71 (d, 7 = 9.0 Hz, 1H), 7.63 - 7.50 (m, 1H), 7.47 - 7.35 (m, 3H), 6.97 (dd, J = 2.1, 9.2 Hz, 1H), 6.73 (d, J = 2.0 Hz, 1H), 3.44 - 3.23 (m, 4H), 2.47 - 2.40 (m, 4H), 2.23 (s, 3H)Experimental details for Compound 91Step-1: Synthesis of tert-butyl (3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazolin-7-yl)carbamate

[0356] To a stirred solution of 3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazoline-7-carboxylic acid (2.5 g, 7.51 mmol) in t-butanol (25 mL) was added DPPA(3.44 g, 12.5 mmol) and triethylamine(4 mL, 30.8 mmol) at room temperature. Resulting reaction mixture was stirred at 80°C for overnight. The reaction mass was cooled to room temperature the volatiles were removed under reduced pressure, the residue was dissolved in water and extracted in to EtOAc. The organic layers was dried over Na2SO4and dried under vacuum to afford crude compound. The crude compound was purified by column chromatography using 8- 12% EtOAc in heptane as eluent to afford tert-butyl (3-(2-chlorophenyl)-4-oxo-2-thioxo-l,2,3,4- tetrahydroquinazolin-7-yl)carbamate (900 mg, 2.23 mmol) as a white solid.

[0357] LC-MS: 99.15% at 2.84 min; 405.2 [M+H]+[Column:EVO C- 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)] .1H NMR (400 MHz, DMSO-d6) δ = 13.05 (s, 1H), 10.06 (s,1H), 7.84 (d, J= 8.7 Hz, 1H), 7.82 - 7.77 (m, 1H), 7.59 (br s, 1H), 7.45 (d, J = 2.6 Hz, 3H), 7.40 - 7.29 (m, 1H), 1.51 (s, 9H).Step-2: Synthesis of 7-amino-3-(2-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 91)

[0358] To a stirred solution of tert-butyl (3-(2-chlorophenyl)-4-oxo-2-thioxo-l ,2,3,4- tctrahydroquinazolin-7-yl)carbamatc (900 mg, 2.22 mmol) in DCM (20 mL) was added TFA (0.83 mL, 12.43 mmol), at 0°C, resulting reaction was stirred at RT for 16 h. progress of the reaction was monitored by TLC. After completion of reaction, reaction mixture concentrated to affordcrude product which was triturated with Dichloromethane and pentane to afford Compound 91 (650 mg, 2.14 mmol) 96% as pale yellow solid.

[0359] LC-MS: 92.00% at 2.17 min; m / z 304.0 [M+H]+[Column:EVO C- 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 2.5 mM NH4OAC in water, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]; HPLC: 91.01% at 8.11 min; [Column:XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ = 12.72 (s, 1H), 7.63 - 7.54 (m, 2H), 7.47 - 7.37 (m, 3H), 6.54 (dd, 7= 2.0, 8.8 Hz, 2H), 6.48 - 6.39 (m, 2H).Experimental Details for l-(2-chlorophenyl)-3-(2-((3-(2-chlorophenyl)-4-oxo-2-thioxo- l,2,3,4-tetrahydroquinazolin-7-yl)oxy)ethyl)thiourea ( Compound 92)Step-1: Synthesis of tert-butyl 4-fluoro-2-nitrobenzoate

[0360] To a stirred solution of 4-fluoro-2-nitrobenzoic acid (5.0 gm, 27.01 mmol) in t- Butanol(25mL) and DCM (25 mL), were added boc anhydride (11 .79 g, 54.02 mmol) and DMAP (0.990 g, 8.10 mmol) at 0 °C and the resulting reaction mixture was stirred at room temperature for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (2x lOOmL). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to obtain crude compound. The crude compound was purified by combi flash column chromatography using 15-20% EtOAc in heptane as eluent to afford tertbutyl 4-fluoro-2-nitrobenzoate (5.5 gm, 22.80 mmol) as an off white solid. Yield: 84%,

[0361] 1H NMR (500 MHz, CDCl3) δ 7.80 (dd, J=8.65, 5.44 Hz, 1 H) 7.50 (dd, J=8.01, 2.24 Hz, 1 H) 7.29 - 7.39 (m, 1 H) 1.52 - 1.58 (m, 9 H)Step-2: Synthesis of tert-butyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-nitrobenzoate

[0362] To a stirred solution of tert-butyl 4-fluoro-2-nitrobenzoate (2.0 gm, 8.29 mmol) and tert-butyl (2-hydroxyethyl)carbamate (2.06 g, 12.43 mmol) in DMF (10 mL) was added K2CO3(2.29 g, 16.59 mmol) at 0 °C and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was diluted with water (50 mL) and extracted with EtOAc (2x 40mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to get crude compound which was purified by combi flash column chromatography using 10-16% EtOAc in heptane as eluent to afford tert-butyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-nitrobenzoate (1.3 gm, 3.40 mmol) as an off white solid. Yield: 41%.

[0363] 1H NMR (400 MHz, DMSO-d6) δ 7.79 (br d, J=8.68 Hz, 1 H) 7.49 (d, J=2.20 Hz, 1 H) 7.28 (dd, J=8.68, 2.32 Hz, 1 H) 7.03 (br s, 1 H) 4.12 (br t, J=5.32 Hz, 2 H) 3.31 (brs, 2 H) 1.47 (s, 9 H) 1.37 (br d, J=3.18 Hz, 9 H); LC-MS: 98.69% at 2.75 min; m / z 400.1 [M+18] [Column: Xsclcct CSH C-18 (150X4.6 mm, 3.5 μm), Mobile Phase- A: 2.5 mM Ammonium Acetate in water, Mobile Phase-B: ACN, Flow rate: 1.0 mL / min (Gradient)];Step-3: Synthesis of tert-butyl 2-amino-4-(2-((tert-butoxycarbonyl)amino)ethoxy)benzoate

[0364] To a stirred solution of tert-butyl 4-(2-((tert-butoxycarbonyl)amino)ethoxy)-2- nitrobenzoate (600 mg, 1.56 mmol) and Fe (522 mg, 9.40 mmol) in MeOH(10 mL) and H2O (2 mL) was added NH4CI (922 mg, 17.24 mmol) at RT and the resulting reaction mixture was stirred at 60 °C for 2 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was filtered through celite pad and washed with DCM (2x 40mL) then water (50 mL), dried over anhydrous Na2SO4, filtered and concentrated to get crude product. The crude compound was purified by combi flash column chromatography using 12-22% EtOAc in heptane as eluent to afford tert-butyl 2-amino-4-(2-((tert- butoxycarbonyl)amino)ethoxy)benzoate (450 mg, 1.27 mmol) as an off white solid, yield: 81%.

[0365] 1H NMR (400 MHz, DMSO-d6) δ ppm 7.56 (d, J=8.93 Hz, 1 H) 6.99 (br s, 1 H) 6.61 (br s, 2 H) 6.22 (d, J=1.96 Hz, 1 H) 6.10 (dd, J=8.93, 2.08 Hz, 1 H) 3.89 (br t, J=5.50 Hz, 2 H) 3.27 (br d, J=5.38 Hz, 2 H) 1.50 (s, 9 H) 1.38 (s, 9 H); LC-MS: 98.48% at 3.13 min; m / z 353.1 [M+H] [Column: EVO C-18 (3.0X50 mm, 2.6pm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)];Synthesis of 2-amino-4-(2-aminoethoxy)benzoic acid

[0366] To a stirred solution of 2-amino 4-(2-((tert-butoxycarbonyl)amino)ethoxy)benzoate (450 mg, 1.27 mmol) in DCM (10 mL) was added TFA (727 mg, 6.38 mmol) at 0 °C and the resulting reaction mixture was stirred at room temperature for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was washed with DCM (2x10 mL) to afford 2-amino-4-(2-aminoethoxy)benzoic acid (200 mg, 1.01 mmol) as an off white solid. Yield: 80%.

[0367] 1H NMR (400 MHz, DMSO-d6) δ 7.99 (br s, 4 H) 7.64 (br d, 7-8.80 Hz, 1 H) 6.27 (s, 1 H) 6.16 (br d, J=8.68 Hz, 1 H) 4.03 - 4.21 (m, 2 H) 3.22 (br d, J=5.01 Hz, 2 H); LC-MS: 79.94% at 0.3 min; m / z 197.1 [M+H] [Column: EVO C-18 (3.0X50 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)];Step-5: Synthesis of l-(2-chlorophenyl)-3-(2-((3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazolin-7-yl)oxy)ethyI)thiourea (Compound 92)

[0368] 2-amino-4-(2-aminocthoxy)bcnzoic acid (200 mg, 1.01 mmol) was dissolved in pyridine (5 mL) and to this was added l-chloro-2-isothiocyanatobenzen 7 (207 mg, 1.22 mmol), the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of stalling materials, the reaction mixture was concentrated under reduced pressure to obtain crude material, which was dissolved in ethanol and the formed solid was filtered and washed with ethanol to afford Compound 92 (70 mg 0.13 mmol) as a white solid, yield: 13%.

[0369] 1H NMR (500 MHz, DMSO-d6) δ 13.03 (br s, 1 H) 9.34 (br s, 1 H) 8.19 (br s, 1 H) 7.92 (d, J=9.27 Hz, 1 H) 7.57 - 7.71 (m, 2 H) 7.42 - 7.53 (m, 4 H) 7.19 - 7.36 (m, 2 H) 6.91 - 7.08 (m, 2 H) 4.28 (br t, J=4.93 Hz, 2 H) 3.93 (br s, 2 H); LC-MS: 98.46% at 2.79 min; m / z 515.0 [M- H] [Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium acetate in water, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.23% at 6.88 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium Acetate, Mobile Phase-B:ACN, Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 93:Synthesis of 7-bromo-3-(2-bromophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 93)

[0370] Compound 93 was prepared from corresponding 2-amino-4-bromobenzoic acid and 1- bromo-2-isothiocyanatobenzene according to the general procedure. (300 mg, 0.73 mmol), yield: 78%. Off white solid

[0371] LC-MS: 96.41% at 2.80 min; m / z 410.9 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)] ; HPLC: 97.94% at 11.49 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (500 MHz, DMSO-d6) δ 13.21 (br s, 1H), 7.90 (d, J = 8.7 Hz, 1H), 7.76 (d, J= 8.1 Hz, 1H), 7.64 (s, 1H), 7.55 - 7.49 (m, 3H), 7.41 - 7.37 (m, 1H).Experimental details for Compound 94:Synthesis of 7-bromo-3-(2-fluorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 94)

[0372] Compound 94 was prepared from corresponding 2-amino-4-bromobenzoic acid and 1- fluoro-2-isothiocyanatobenzene according to step 1 method-B general procedure as off white solid (50 mg, 0.142 mmol), yield: 15%.

[0373] LC-MS: 96.40% at 2.72 min; m / z 350.9 [M+H]+[Column:EVO C- 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)] ; HPLC: 97.01% at 7.41 min; [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ 13.24 (br s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.63 (s, 1H), 7.55 - 7.42 (m, 3H), 7.40 - 7.30 (m, 2H)Experimental details for Compound 95Step 1: Synthesis of methyl 4-bromo-5-fluoro-2-nitrobenzoate

[0374] To a stirred solution of 4-bromo-5-fluoro-2-nitrobenzoic acid (3 g, 11.3 mmol) in methanol (30mL) was added H2SO4(3.9 mL, 79.1 mol) at 0 °C and the resulting reaction mixtue was stirred at 60 °C for 16 h, progress of the reaction was monitored by TLC. After complete consumption of starting materials, methanol was concentrated under reduced pressure and the resulting residue was diluted with water to afford solid material, which was filtered and dried under vacuum to afford methyl 4-bromo-5-fluoro-2-nitrobenzoate (2.5 g, 8.99 mmol) as an off white solid. Yield: 79%.Step 2: Synthesis of methyl 2-amino-4-bromo-5-fluorobenzoate

[0375] To a solution of methyl 4-bromo-5-fluoro-2-nitrobenzoate (2.5 g, 8.99 mmol) in methanol (24 mL) and water (6 mL) were added iron (3.01 g, 53.95 mmol) and ammonium chloride (5.29 g, 98.9 mmol) at rt and the resultant reaction mixture was stirred at 60 °C for 2 h. progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was cooled to RT and filtered through celite bed, washed with dichloromethane. The obtained Filtrate was washed with water and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford pale brown liquid which was purified by column chromatography using 10-15% EtOAc in heptane to afford methyl 2-amino-4-bromo-5- fluorobenzoate (1 .5 g, 6.0 mmol, 67% yield) as a pale-yellow solid.

[0376] LC-MS: 94.96 % at 2.73 min; m / z 250.9 [M+H]+[Column :Kinetex EVO-C 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]Step 2: Synthesis of 7-bromo-3-(2-chlorophenyl)-6-fluoro-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one (Compound 95):

[0377] Compound 95 was prepared from corresponding methyl 2-amino-4-bromo-5- fluorobenzoate and l-chloro-2-isothiocyanatobenzene according to step 1 method-B general procedure. Off white solid (80 mg, 0.20 mmol), Yield: 17%.

[0378] LC-MS: 97.48 % at 2.83 min; m / z 384.9 [M-H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACNT / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min (Gradient)] HPLC: 98.26 % at 11.61 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:WATER]1H NMR (500 MHz, DMSO-d6) δ 13.27 (s, 1 H), 7.83 (d, J=8.11 Hz, 1 H), 7.73 (d, J=5.80 Hz, 1 H), 7.58 - 7.63 (m, 1 H), 7.46 (d, J=2.90 Hz, 4 H).Experimental details for Compound 96Step 1: Synthesis of methyl 2-amino-4-bromobenzoate

[0379] To a stirred solution of 2-amino-4-bromobenzoic acid (3 g, 13.8 mmol) in methanol (30mL) was added H2SO4(4.4 mL, 83.2 mol) at 0 °C and the resulting reaction mixtue was stirred at 60 °C for 16 h, progress of the reaction was monitored by TLC. After complete consumption of starting materials, methanol was evaporated under reduced pressure, the obtained residue was diluted with water and filtered, the obtained solids were dried under vacuum to afford methyl 2- amino-4-bromobenzoate (3g, 13.04 mmol) as an off white solid. Yeild 93%.Step 2: Synthesis of methyl 4-bromo-2-isothiocyanatobenzoate

[0380] To a stirred solution of methyl 2-amino-4-bromobenzoate (1 g, 4.34 mmol) in THF(20 mL) were added Et3N(2.47 mL, 17.7 mmol) and thiopho sgene(600 mg, 5.21 mmol) at 0 °C andthe resulatant reaction mixture was stirerd at rt for 16 h. Progress of the reaction was manitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ethylacetate and washed with water, dried over anhydrous Na2SO4and concentrated under reduced pressure to obtain crude product, which was purified by flash column chromatography using 3-8% EtOAc in hexane as eluent to afford methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (700 mg, 2.57 mmol) as a pale brown solid. Yield: 59%.

[0381] 1H NMR (400 MHz, DMSO-d6) δ = 7.97 - 7.81 (m, 2H), 7.71 (dd, J = 2.0, 8.6 Hz, 1H), 3.88 (s, 3H).Step 3: Synthesis of 7-bromo-3-(2-chloro-4-fluorophenyl)-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one (Compound 96)):

[0382] Compound 96 was prepared from corresponding methyl 4-bromo-2- isothiocyanatobenzoate and 2-chloro-4-fluoroaniline according to the general procedure. Pale brown solid (90 mg, 0.23 mmol) Yield: 32%.

[0383] LC-MS: 99.72 % at 2.86 min; m / z 384.9 [M-H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)] HPLC: 99.83 % at 11.15 min [Column:XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 5mM Ammonium bicarbonate Mobile Phase-B: ACN Program T / B%: 0.01 / 20,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: WATER:ACN ]1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1 H), 7.89 (d, J=8.44 Hz, 1 H), 7.63 - 7.67 (m, 2 H), 7.53 - 7.60 (m, 2 H), 7.38 (td, J=8.56, 2.81 Hz, 1 H).Experimental details for Compound 97Synthesis of 7-bromo-3-(2-chloro-3-fluorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)- one (Compound 97):

[0384] Compound 97 was prepared from corresponding methyl 4-bromo-2- isothiocyanatobenzoate (common intermediate) and 2-chloro-3-fluoroaniline according to the general procedure. Pale brown solid (90 mg, 0.23 mmol), Yield: 32%.

[0385] LC-MS: 99.66 % at 2.85 min; m / z 386.9 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACNT / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)] HPLC: 98.08 % at 9.98 min [Column:XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase A: 5 mM Ammonium bicarbonate; Mobile Phase-B: ACN Program T / B%: 0.01 / 20,12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: WATER:ACN]1H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1 H), 7.90 (d, J=8.44 Hz, 1 H), 7.64 (d, J=1.22 Hz, 1 H), 7.52 - 7.57 (m, 3 H), 7.38 - 7.43 (m, 1 H).Experimental details for Compound 98Synthesis of 7-bromo-3-(2-chloro-5-fluorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)- one (Compound 98)

[0386] To a stirred solution of 2-chloro-5-fluoroaniline (106 mg, 0.72 mmol) and triethylamine (0.199 mL, 1.44 mmol) in t-butanol (10 mL) was added 4-bromo-2- isothiocyanatobenzoate (Common intermediate) (200 mg, 0.73 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to get crude product which was purified by combi flash column chromatography using 18% EtOAc in heptane as eluent to afford Compound 98 (170 mg, 0.44 mmol) as pale brown solid. Yield: 61%.

[0387] 1H NMR (500 MHz, DMSO-d6) δ 13.29 (s, 1 H) 7.90 (d, J=8.69 Hz, 1 H) 7.62 - 7.73 (m, 2 H) 7.50 - 7.59 (m, 2 H) 7.39 (td, J=8.40, 2.90 Hz, 1 H); LC-MS: 96.31% at 2.85 min; m / z 384.9 [M+H]+[Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Aq. Formic acid, Mobile Phasc-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 96.34% at 11.69 min[Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 99Synthesis of 7-bromo-3-(2-chloro-6-fluorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)- one (Compound 99)

[0388] To a stirred solution of 2-chloro-6-fluoroaniline (159 mg, 1.10 mmol) and triethylamine (0.3 mL, 2.2 mmol) in t-butanol (10 mL) was added 4-bromo-2- isothiocyanatobenzoate (Common intermediate) (300 mg, 1.1 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was cooled to room temperature and concentrated under reduced pressure to get crude product which was purified by combi flash column chromatography using 18-20% EtOAc in heptane as eluent to afford Compound 99 (240 mg, 0.62 mmol) as a pale-yellow solid. Yield:56%.

[0389] 1H NMR (400 MHz, DMSO-d6) δ 13.48 (br s, 1 H) 7.92 (d, J=8.38 Hz, 1 H) 7.65 (d, J=1.75 Hz, 1 H) 7.51 - 7.63 (m, 3 H) 7.44-7.46 (m, 1 H); LC-MS: 99.48% at 2.88 min; m / z 386.8 [M+H] [Column: EVO Cl 8 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradient)] ; HPLC: 99.93% at 11.91 min [Column: X- Select CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 100Synthesis of 7-bromo-3-(2,3-dichlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one(Compound 100)

[0390] To a stirred solution of 2,3-dichloroaniline (120 mg, 0.73 mmol) and triethylamine (0.2 mL, 1.46 mmol) in t-butanol (5 mL) was added 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (200 mg, 0.73 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was cooled to room temperature and concentrated under reduced pressure to get crude product which was purified by combi flash column chromatography using 16-20% EtOAc in heptane as eluent to afford Compound 100 (60 mg, 0.15 mmol) as a white solid. Yield 20%.

[0391] 1H NMR (400 MHz, DMSO-d6) δ 13.30 (br s, 1 H) 7.90 (d, J=8.44 Hz, 1 H) 7.75 (dd, J=6.72, 2.69 Hz, 1 H) 7.64 (d, J=0.98 Hz, 1 H) 7.47 - 7.59 (m, 3 H); LC-MS: 99.82% at 2.97 min; m / z 400.9 [M+H]+[Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Aq. Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 99.98% at 7.62 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium Acetate, Mobile Phasc-B: ACN, Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 101Synthesis of 7-bromo-3-(2,4-dichlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 101):

[0392] Compound 101 was prepared from corresponding 4-bromo-2-isothiocyanatobenzoate (common intermediate) and 2,4-dichloroaniline according to the general procedure. Pale brown solid (120 mg, 0.30 mmol) Yield: 40%.

[0393] LC-MS: 99.04 % at 3.01 min; m / z 401.9 [M-H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%:0.01 / 5, 3 / 90, 5 / 90, 5.5 / 5, 6 / 5 Flow rate: 0.8 mL / min(Gradient)] HPLC: 98.85 % at 10.35 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05)

[0394] Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,8 / 80, 12 / 90,16 / 90. Flow: 1.0 mL / min. Diluent: ACN:WATER]1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1 H), 7.90 (d, J=8.50 Hz, 1 H), 7.83 (d, J=2.00 Hz, 1 H), 7.53 - 7.65 (m, 4 H).Experimental details for Compound 102Synthesis of 7-bromo-3-(2,5-dichlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 102)

[0395] To a stirred solution of 2,5-dichloroaniline (120 mg, 0.73 mmol) and triethylamine (0.2 mL, 1.46 mmol) in t-butanol (5 mL) was added methyl4-bromo-2-isothiocyanatobenzoate (Common inteimediate) (200 mg, 0.73 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was cooled to room temperature and concentrated under reduced pressure to get crude product which was purified by combi flash column chromatography using 17-20% EtOAc in heptane as eluent to afford Compound 102 (90 mg, 0.22 mmol) as a white solid. Yield 30%.

[0396] 1H NMR (400 MHz, DMSO-d6) δ 13.30 (br s, 1 H) 7.90 (d, J=8.44 Hz, 1 H) 7.62 - 7.76 (m, 3 H) 7.53-7.58 (m, 2 H); LC-MS: 98.49% at 2.98 min; m / z 400.9 [M+H]+[Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Aq. Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min (Gradient)]; HPLC: 98.67% at 10.63 min [Column: XSELECT CSH C 18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 103Synthesis of 7-bromo-3-(2-chloro-3-methoxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)- one (Compound 103)

[0397] To a stirred solution of 2-chloro-3-methoxyaniline (173 mg, 1.10 mmol) in pyridine (5 mL) was added methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (200 mg, 0.73mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was cooled to room temperature and concentrated under reduced pressure to get crude product which was purified by combi flash column chromatography using 17-25% EtOAc in heptane as eluent to afford Compound 103 (60 mg, 0.15 mmol) as an off white solid. Yield 14%.

[0398] 1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1 H) 7.88 (d, J=8.51 Hz, 1 H) 7.63 (d, J=1.75 Hz, 1 H) 7.53 (dd, J=8.44, 1.81 Hz, 1 H) 7.36 - 7.47 (m, 1 H) 7.23 (dd, J=8.44, 1.19 Hz, 1 H) 7.07 (dd, J=7.88, 1.25 Hz, 1 H) 3.92 (s, 3 H); LC-MS: 95.6% at 2.76 min; m / z 398.9 [M+H] [Column: EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase- B: ACN, Flow rate: 0.8 mL / min(Gradient)]; HPLC: 94.81% at 11.13 min [Column: X-Select CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water]Experimental details for Compound 104Synthesis of 7-bromo-3-(2-chloro-4-methoxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH),- one (Compound 104):

[0399] Compound 104 was prepared from corresponding methyl 4-bromo-2- isothiocyanatobenzoate (Common intermediate) and 2-chloro-4-methoxyaniline according to the general procedure. Brown solid (162 mg, 0.41 mmol) Yield: 56%.

[0400] LC-MS: 99.78 % at 2.83 min; m / z 398.9 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)] HPLC: 99.95 % at 11.59 min [Column :XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ)Mobile Phase-A: 5 mM Ammonium Bicarbonate , Mobile Phase-B: Acetonitrile Program T / B%: 0.01 / 20,12 / 90,16 / 90, Flow: 1.0 mL / min. (Diluent: WATER:ACN )]1H NMR (400 MHz, DMSO-d6) δ 13.17 (s, 1 H), 7.88 (d, J=8.50 Hz, 1 H), 7.63 (d, J=1.50 Hz, 1 H), 7.53 (dd, J=8.50, 1.25 Hz, 1 H), 7.37 (d, J=8.76 Hz, 1 H), 7.19 (d, J=2.63 Hz, 1 H), 7.03 (dd, J=8.82, 2.56 Hz, 1 H), 3.84 (s, 3 H).Experimental details for Compound 105Step 1: methyl 2-chIoro-3-nitrobenzoate

[0401] To a stirred solution of 2-chloro-3-nitrobenzoic acid (3 g, 14.8 mmol) in methanol (50mL) was added H2SO4(4.59 mL, 88.8 mol) at 0 °C and the resulting reaction mixture was stirred at 60 °C for 16 h. progress of the reaction was monitored by TLC. After complete consumption of stalling materials, the methanol was evaporated under reduced pressure, the obtained residue was diluted with water and filtered the obtained solids, dried under vacuum to afford methyl 2-chloro-3 -nitrobenzoate (3g, 13.9 mmol, 93%) as an off white solid.Step-2: methyl 3-amino-2-chlorobenzoate

[0402] To a solution of methyl 2-chloro-3-nitrobenzoate (3 g, 13.9 mmol) in methanol (30 mL) and water (15 mL) were added iron (3.8 g, 69.5 mmol) and ammonium chloride (7.44 g, 139.9 mmol) at rt and the reaction mixture was stirred at 60 °C for 2h. After completion of stalling materials the reaction mixture was cooled to RT and filtered through celite bed and washed with dichloromethane. Filtrate was washed with water and organic layer was dried over anhydrous Na2SO4, filtered and concentrated to afford methyl 3-amino-2-chlorobenzoate (1.5 g, 8.08 mmol, 58%) as a pale brown liquid which was used directly for next reaction without any further purification.

[0403] LC-MS: 99.25% at 2.80 min; m / z 186.00 [M-H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase A: 2.5 mM NH4OAC in water; Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min (Gradient)].Step-3: methyl 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H),-yl)-2- chlorobenzoate (Compound 105):

[0404] Compound 105 was prepared from corresponding methyl 4-bromo-2- isothiocyanatobenzoate (Common intermediate) and methyl 3-amino-2-chlorobenzoate according to the general procedure. Off white solid (1 g, 2.35 mmol) Yield: 29%.

[0405] LC-MS: 97.51% at 3.24 min; m / z 424.8 [M-H]+[Column: EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase A: 2.5 mM NH4OAC in water; Mobile Phase-B: ACN T / B%:0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)] HPLC: 98.48 % at 11.12 min Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ)Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,12 / 90,16 / 90, Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)]1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1 H), 7.86 - 7.92 (m, 2 H), 7.73 (dd, J=7.89, 1.65 Hz, 1 H), 7.65 (d, J=1.71 Hz, 1 H), 7.54 - 7.62 (m, 2 H), 3.89 (s, 3 H).Experimental details for Compounds 106, 107 and 108Step-1: Synthesis of methyl 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4- chlorobenzoate (Compound 106)

[0406] Methyl 3-amino-4-chlorobenzoate (1 g, 5.40 mmol) was dissolved in pyridine (8 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (common intermediate) (1.47 g, 5.40mmol), the resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was dissolved in dichloromethane and pentane was added. The solid formed was removed by filtration and solid was washed with pentane to afford methyl 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chlorobenzoate (Compound 106) (1.1 g, 2.58 mmol) as an off white solid. Yield: 48%.

[0407] 1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1 H) 8.15 (d, J=2.00 Hz, 1 H) 8.03 (dd, J=8.38, 2.13 Hz, 1 H) 7.89 (d, J=8.50 Hz, 1 H) 7.80 (d, J=8.38 Hz, 1 H) 7.64 (d, J=1.75 Hz, 1 H) 7.55 (dd, J=8.44, 1.81 Hz, 1 H) 3.88 (s, 3 H); LC-MS: 95.19% at 3.22 min; m / z 424.8 [M+H] [Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium acetate in water, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradient)]; HPLC: 98.50% at 10.48 min[Column: X-Select CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium Acetate;Mobile Phase-B: ACN; Flow: 1.0 mL / min, Diluent: ACN:Water];Step-2: Synthesis of 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4- chlorobenzoic acid (Compound 107)

[0408] To a solution of methyl 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)- 4-chlorobenzoate (compound 106) (700mg, 1.64 mmol) in THF (3 mL), Methanol (6mL) and H2O (3 mL) was added LiOH.H2O (82 mg, 1.97 mmol eq) at 0 °C and the reaction mixture was stirred at 60 °C for 2h. Progress of the reaction was monitored by TLC. After completion of stalling materials, volatiles were removed under vacuum and adjusted the pH of aqueous layer to 4 with 2N aq.HCl and stirred for 10 min. solid was precipitated out which was separated and dried under vacuum to afford 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chlorobenzoic acid (Compound 107) (550 mg, 1.33 mmol) as an off white solid. Yield: 81%.

[0409] 1H NMR (400 MHz, DMSO-d6) δ 13.27 (br s, 2 H) 8.09 (br s, 1 H) 8.00 (br d, J=8.13 Hz, 1 H) 7.90 (br d, J=8.25 Hz, 1 H) 7.76 (br d, J=8.25 Hz, 1 H) 7.64 (s, 1 H) 7.55 (br d, J=8.25 Hz, 1 H); LC-MS: 95.32% at 2.53 min; m / z 413.0 [M+H] [Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradient)]; HPLC: 94.17% at 10.32 min [Column: X-Select CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05); Mobile Phase-B: ACN:0.05% TFA (95:05); Flow: 1.0 mL / min, Diluent: ACN:Water];Step-3: Synthesis of 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4- chlorobenzamide (Compound 108)

[0410] 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chlorobenzoic acid (Compound 107) (300 mg, 0.73 mmol) was dissolved in DMF (6 mL) and to this mixture were added NH4Cl (96mg, 1.82 mmol), EDC.HCl (210 mg, 1.09 mmol) and DMAP (267 mg, 2.19 mmol) at 0 °C and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of starting material, the reaction mixture was diluted with water (40 mL). The formed solid was filtered and solid was washed with water and dried under vacuum to afford 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4- chlorobenzamide (Compound 108) (50 mg, 0.12 mmol) off white solid. Yield: 16%.

[0411] 1H NMR (400 MHz, DMSO-d6) δ 13.32 (s, 1 H) 8.09 (br s, 1 H) 7.96 - 8.03 (m, 2 H) 7.92 (d, J=8.44 Hz, 1 H) 7.75 (d, J=8.19 Hz, 1 H) 7.66 (d, J=1.71 Hz, 1 H) 7.53 - 7.61 (m, 2 H);LC-MS: 99.14% at 2.89 min; m / z 407.8 [M-H] [Column: EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium acetate in water, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradient)]; HPLC: 99.84% at 6.99 min [Column: X-Select CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium Bicarbonate; Mobile Phase-B: ACN; Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 1093-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H),-yl)-2-chlorobenzoic acid

[0412] To a stirred solution of Compound 105 (900 mg, 2.11 mmol) in THF (20 mL) and H2O (10 mL) was added LiOH. H2O (177mg, 4.20 mmol) at 0 °C and the reaction mixture was stirred at 60 °C for 1 h. Progress of the reaction was monitored by TLC. After completion of starting materials, THF was distilled off under vacuum and diluted with water (40 mL), the aqueous layer was washed with Ethylacetate (2x30mL) and adjusted the pH to 2 with IN aq. HCl, stirred for 5 min, the formed solid was filtered and washed with heptane to afford 3-(7-bromo-4-oxo-2-thioxo- l,4-dihydroquinazolin-3(2H)-yl)-2-chlorobenzoic acid (700 mg, 1.70 mmol) as white solid, yield 80%.

[0413] LC-MS: 99.23 % at 2.73 min; m / z 412.9 [M+H]+[Column :Kinetex Xselect CSH- C18(3.0X50 mm, 2.5 μm Mobile Phase-A: 0.025%Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)] HPLC: 97.62 % at 9.61 min Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B% : 0.01 / 10,12 / 90,16 / 90, Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)]1H NMR (400 MHz, DMSO-d6) δ 13.49 - 13.64 (br, 1 H), 13.27 (s, 1 H), 7.84 - 7.92 (m, 2 H), 7.63 - 7.69 (m, 2 H), 7.53 - 7.58 (m, 2 H).3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-2-chlorobenzamide (Compound 109)

[0414] To a solution of 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-2- chlorobenzoic acid (300 mg, 0.72 mmol) in DMF (5 mL), NH4CI (154 mg, 2.91 mmol), DMAP (355 mg, 2.91) and EDC (273 mg, 1.44 mmol) were added slowly at 0 °C and the reaction mixturewas stirred at room temperature for 12 h. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x20 mL). The combined organic layer was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography to afford Compound 109 (30 mg, 0.073 mmol, 10%).

[0415] LC-MS: 97.07 % at 1.65 min; m / z 409.9 [M-H]+[Column:ASCENTIS EXPRESS C18(5 cmX2.1 mm, 2.7 μ) Mobile Phase-A: 2 mM Ammonium Acetate in Water. Mobile Phase- B: ACN T / B%: 0.01 / 5,2 / 98,3 / 98,3.2 / 5,4 / 5. Flow rate: 1.2 mL / min(Gradient)] HPLC: 97.73 % at 5.74 min Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10, 12 / 90,16 / 90., Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)]1H NMR (400 MHz, DMSO- d6) δ ppm 13.23 (s, 1 H), 7.99 (s, 1 H), 7.89 (d, J=8.44 Hz, 1 H), 7.60 - 7.65 (m, 2 H), 7.49 - 7.57 (m, 4 H).Experimental details for Compounds 110 and 111

[0416] Step-1: To a solution of methyl 2-amino-3-chlorobenzoate (1 g, 5.40 mmol) in DCM (10 mL), were added triethylamine (1.63 g, 16.21 mmol) and Thiophosgene (1.24 g, 10.80 mmol) at 0 °C and the resulting reaction mixture was stirred at room temperature for 2 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was diluted with ice cold water (100 mL) and extracted with ethyl acetate (2x200 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to afford methyl 3- chloro-2-isothiocyanatobenzoate (800 mg, 3.52 mmol, 65%).

[0417] LC-MS: 99.62 % at 3.02 min; m / z 228.1 [M+H]+[Column :Kinetex EVO-C 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]

[0418] Step-2: methyl 3-chloro-2-isothiocyanatobenzoate (800 mg, 3.52 mmol) was dissolved in pyridine (10 mL) and to this was added SM-2 (760 mg, 3.52 mmol), resulting mixture was stirred for 16 h at 80 °C. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography to afford Compound 110 (150 mg, 0.35 mmol, 10%).

[0419] LC-MS: 52.37 % at 2.87 min; m / z 427.0 [M+H]+[Column :Kinetex EVO-C 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]

[0420] Step-3: To a solution of Compound 110 (120 mg, 0.28 mmol) in THF (10 mL) and H2O (10 mL) was added LiOH.H2O (18 mg, 0.56 mmol) at 0 °C and the reaction mixture was stirred at 60 °C for 2 h. Progress of reaction was monitored by TLC. After completion of starling materials, the THF was distilled off under vacuum and diluted with water (40 mL), the aqueous layer was washed with Ethylacetate (2x30 mL) and adjusted the pH to 2 with IN aq. HCl, stirred for 5 min, the formed solid was filtered and washed with heptane to afford 2-(7-bromo-4-oxo-2- thioxo-l,4-dihydroquinazolin-3(2H)-yl)-3-chlorobenzoic acid (20 mg, 0.048 mmol, 17%).

[0421] LC-MS: 86.83% at 1.92 min; m / z 410.9 [M-H]+[Column:Xselect CSH-C18 (3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase- B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient)] HPLC: 94.94 % at 4.96 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 5 mM Ammonium Bicarbonate , Mobile Phase-B: ACN Program T / B%: 0.01 / 10, 12 / 90,16 / 90., Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)]

[0422] 1H NMR (400 MHz, DMSO-d6) δ 13.27 (s, 1 H), 8.04 (dd, J=7.75, 1.25 Hz, 1 H), 7.88 - 7.93 (m, 2 H), 7.60 - 7.66 (m, 2 H), 7.55 - 7.60 (m, 1 H).

[0423] Step-4: To a solution of 2-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)- 3-chlorobenzoic acid (100 mg, 0.24 mmol) in DMF (5 mL), NH4CI (51 mg, 0.97 mmol), DMAP (118 mg, 0.97) and EDC (273 mg, 1.44 mmol) were added slowly at 0 °C and the reaction mixture was stirred at room temperature for 12 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was diluted with ice cold water (50 mL) andextracted with ethyl acetate (2x20 mL). The combined organic layer was concentrated under reduced pressure to obtain compound, which was purified by combi flash column chromatography to afford Compound 111 (20 mg, 0.048 mmol, 20%).

[0424] LC-MS: 99.54 % at 2.08 min; m / z 409.9 [M-H]+[Column :KINETEX EVO C18(5 cmX3.0 mm, 2.6 μ) Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN; Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN T / B%:0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient)] HPLC: 97.92 % at 5.04 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 5 mM Ammonium Bicarbonate , Mobile Phase-B: ACN Program T / B%: 0.01 / 10, 12 / 90,16 / 90., Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)]1H NMR (400 MHz, DMSO-d6) δ 13.14 (s, 1 H), 7.89 (d, J=8.38 Hz, 2 H), 7.75 (d, J=14.60, 7.91, 1.25 Hz, 2 H), 7.63 (d, J=1.75 Hz, 1 H), 7.53 - 7.58 (m, 2 H), 7.29 (s, 1 H).Experimental details for Compounds 112 and 113Synthesis of 7-bromo-3-(2-chloro-5-nitrophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 112)

[0425] To a stirred solution of 2-chloro-5-nitroaniline (2 g, 11.6 mmol) in THF (20 mL) was added EtsN (3.22 mL, 23.2 mmol), thiophosgene(0.97 mL, 12.76 mmol) at 0 °C. Resultant reaction mixture was stirred at RT for 16 h. Progress of the reaction was monitored by TLC. Reaction was diluted with ethylaceate (70mL) and washed with water (3x50 mL), dried over anhydrous Na2SO4and concentrated, purified by combi flash chromatography using 2-5% EtOAc in heptane as eluent to afford l-chloro-2-isothiocyanato-4-nitrobenzene (1.2 g, 5.6 mmol) as pale brown solid. Yield: 48%.

[0426] 1H NMR (400 MHz, CDCl3) δ 8.00 - 8.13 (m, 2 H) 7.61 (d, J=8.75 Hz, 1 H)

[0427] 2-amino-4-bromobenzoic acid (1.1 g, 5.12 mmol) was dissolved in pyridine (12 mL) and to this was added l-chloro-2-isothiocyanato-4-nitrobenzene (1.1 g, 5.12 mmol), resulting mixture was stirred for 16 h at 80 °C. After completion of the starting materials, the reaction mixture was concentrated to obtain crude compound, which was purified by trituration with DCM and pentane twice to afford 7-bromo-3-(2-chloro-5-nitrophenyl)-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one (Compound 112) (850 mg, 2.07 mmol) as a pale brown solid. Yield:40%.

[0428] 1H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1 H) 8.59 (d, J=2.69 Hz, 1 H) 8.35 (dd, J=8.93, 2.69 Hz, 1 H) 7.88 - 8.00 (m, 2 H) 7.66 (d, J=1.59 Hz, 1 H) 7.57 (dd, J=8.44, 1.71 Hz, 1 H); LC-MS: 95.72% at 2.57 min; m / z 411.7 [M-H] [Column: KINETEX EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in 1000 mL in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 95.87% at 11.53 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phasc-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN: Water];3-(5-amino-2-chlorophenyl)-7-bromo-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 113)

[0429] To a solution of 7-bromo-3-(2-chloro-5-nitrophenyl)-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one (compound 112)(250 mg, 0.58 mmol) in ethanol was added SnC12.2H2O (265 mg, 1.16 mmol) was added and the resulting reaction mixture was stirred for 2h at 75 °C. The progress of the reaction was monitored by TLC. After completion of starting materials. The reaction mixture was concentrated under reduced pressure and diluted with saturated sodium bicarbonate solution, extracted with ethyl acetate(2X40 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to get crude product which was purified by column chromatography to afford Compound 113 (80 mg, 0.20 mmol) as a pale-yellow solid. Yield: 35%.

[0430] 1H NMR (400 MHz, DMSO-d6) δ 13.10 (br s, 1 H) 7.87 (d, J=8.50 Hz, 1 H) 7.61 (d, J=1.75 Hz, 1 H) 7.52 (dd, J=8.44, 1.69 Hz, 1 H) 7.17 (d, J=8.63 Hz, 1 H) 6.62 (dd, J=8.63, 2.63 Hz, 1 H) 6.56 (d, J=2.63 Hz, 1 H) 5.41 (s, 2 H); LC-MS: 99.73% at 2.02 min; m / z 381.9 [M+H]+[Column: KINETEX EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 96.60% at 8.46 min [Column: XSELECT CSH C18 (150 X 4.6 mm,3.5 μ), Mobile Phase-A: 5 mM Ammonium bicarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 114

[0431] Step-1: To a solution of 3-chloro-2-nitroaniline (1 g, 5.81 mmol) in DMF (10 mL), DMAP (709 mg, 5.81 mmol) and (Boc)2O (3.79 g, 17.43 mmol) were added slowly at 0 °C and the reaction mixture was stirred at room temperature for 16 h. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ice cold water (300 mL) and extracted with ethyl acetate (2x200 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford tert-butyl (tert- butoxycarbonyl)(3-chloro-2-nitrophenyl)carbamate (1.2 g, 3.22 mmol, 55%).

[0432] Step-2: To a solution of tert-butyl (tert-butoxycarbonyl)(3-chloro-2- nitrophenyl)carbamate (1.2 g, 3.22 mmol) in methanol (10 mL) and water (5 mL) were added iron (887 mg, 16.12 mmol) and ammonium chloride (1.7 g, 32.20 mmol) at rt and the reaction mixture was stirred at 80 °C for 3 h. Progress of the reaction monitored by TLC. After completion of starting materials, the reaction mixture was cooled to RT and filtered through celite bed and washed with ethyl acetate. Filtrate was washed with water and concentrated to afford pale brown liquid which was triturated with hexane to afford tert-butyl (2-amino-3-chlorophenyl)(tert- butoxycarbonyl)carbamate (800 mg, 2.33 mmol).

[0433] LC-MS: 54.68 % at 3.09 min; m / z 187.1 [M-56]+[Column :Kinctcx EVO-C 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN

[0434] T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]

[0435] Step-3: tert-butyl (2-amino-3-chlorophenyl)(tert-butoxycarbonyl)carbamate (200 mg, 0.58 mmol) was dissolved in pyridine (5 mL) and to this was added methyl 4-bromo-2- isothiocyanatobenzoate (159 mg, 0.58 mmol), resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated to afford crude compound of tert-butyl (2-(7-bromo-4-oxo-2-thioxo-l,4- dihydroquinazolin-3(2H)-yl)-3-chlorophenyl)(tert-butoxycarbonyl)carbamate (150 mg, 0.25 mmol).

[0436] LC-MS: 39.56 % at 2.53 min; m / z 428.0 [M-56]+[Column :Kinetex EVO-C 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025%Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]

[0437] Step-4: To a stirred solution of tert-butyl (2-(7-bromo-4-oxo-2-thioxo-l,4- dihydroquinazolin-3(2H)-yl)-3-chlorophenyl)(tert-butoxycarbonyl)carbamate (150 mg, 0.25 mmol) in DCM (5 mL) was added TFA (1 mL) at 0°C, resulting reaction was stirred at RT for 2 h. progress of the reaction was monitored by TLC. After completion of stalling materials, the reaction mixture was concentrated to afford crude product, which was triturated with Dichloromethane and pentane to afford Compound 114 (30 mg, 0.07 mmol, 30%).

[0438] LC-MS: 97.16 % at 2.58 min; m / z 384.00 [M+H]+[Column:EVO C-18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 2.5 mM NH4OAC in water, Mobile Phase-B: ACN, T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient).] HPLC: 98.39 % at 10.18 min Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10, 12 / 90,16 / 90., Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)]1H NMR (400 MHz, DMSO-d6) δ ppm 13.02 (s, 1 H), 7.86 (d, J=8.44 Hz, 1 H), 7.60 (s, 1 H), 7.48 - 7.52 (m, 1 H), 7.05 (t, J=8.01 Hz, 1 H), 6.63 (t, J=7.46 Hz, 2 H), 5.60 (s, 2 H).Experimental details for Compound 115

[0439] Step-1: To a stirred solution of tert-butyl (2-chloro-3-nitrophenyl)carbamate (900 mg, 3.30 mmol) in DCM (5 mL) was added TFA (1 mL) at 0°C, the resulting reaction was stirred at RT for 2 h. progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture concentrated to afford crude product which was triturated with Dichloromethane and pentane to afford 2-chloro-3-nitroaniline (700 mg, 4.06 mmol, 81%).

[0440] LC-MS: 91.52 % at 2.71 min; m / z 173.0 [M-H]+[Column:X-Select CHS C18(3.0X50 mm, 2.5 μ) Mobile Phase-A: 2 mM Ammonium bicarbonate in Water. Mobile Phase-B: ACN T / B%: 0.01 / 0,2 / 98,3 / 98,3.2 / 0,4 / 0. Flow rate: 1.2 mL / min(Gradient)]

[0441] Step-2: To a solution of 2-chloro-3-nitroaniline (600 mg, 3.48 mmol) in DMF (10 mL), NaH (418 mg, 10.46 mmol) and Mel (1.50 g, 10.46 mmol) were added slowly at 0 °C and the reaction mixture was stirred at room temperature for 16 h. Progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with ice cold water (300 mL) and extracted with ethyl acetate (2x200 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to afford 2-chloro-N,N-dimethyl-3-nitroaniline (560 mg, 2.80 mmol).

[0442] LC-MS: 63.85 % at 2.01 min; m / z 201.10 [M-H]+[Column:Xselect CSH-C 18(3.0X50 mm, 2.5 μm) Mobile Phasc-A: 0.5 mL Formic acid in 950 mL watcr+50 mL ACN,

[0443] B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient)]

[0444] Step-3: To a solution of 2-chloro-N,N-dimethyl-3-nitroaniline (560 mg, 2.80 mmol) in methanol (10 mL) and water (5 mL) were added iron (770 mg, 14.00 mmol) and ammonium chloride (1.48 g, 28.00 mmol) at rt and the reaction mixture was stirred at 80 °C for 3h. Progress of the reaction was monitored by TLC. After completion of stalling materials the reaction mixturewas cooled to RT and filtered through celite bed, washed with ethyl acetate. Filtrate was washed with water and dried over anhydrous Na2SO4, filtered and concentrated to afford pale brown liquid which was triturated with hexane to afford 2-chloro-N1,N1-dimethylbenzene-l,3-diamine (480 mg, 2.82 mmol).

[0445] LC-MS: 63.85 % at 0.46 min; m / z 171.2 [M-H]+[Column:Xselect CSH-C18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase- B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2, Flow rate: 1.2 mL / min(Gradient)]

[0446] Step-4: 2-chloro-N1,N1-dimethylbenzene-l,3-diamine (460 mg, 2.70 mmol) was dissolved in pyridine (10 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (735 mg, 2.70 mmol), the resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of stalling materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography to afford Compound 115 (200 mg, 0.48 mmol, 18%).

[0447] LC-MS: 99.77 % at 2.32 min; m / z 411.8 [M+H]+[Column:ASCENTIS EXPRESS C18(5 cmX2.1 mm, 2.7 μ) Mobile Phase-A: 2 mM Ammonium Acetate in Water. Mobile Phase- B: ACN T / B%: 0.01 / 5,2 / 98,3 / 98,3.2 / 5,4 / 5. Flow rate: 1.2 mL / min(Gradient)] HPLC: 98.26% at 7.68 min Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: ACN:0.05% TFA (95:05) Program T / B%: 0.01 / 10,12 / 90,16 / 90., Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)].1H NMR (400 MHz, DMSO-d6) δ ppm 13.17 (s, 1 H), 7.88 (d, J=8.50 Hz, 1 H), 7.63 (d, J=1.63 Hz, 1 H), 7.53 (dd, J=8.44, 1.69 Hz, 1 H), 7.34 - 7.41 (m, 1 H), 7.23 (dd, J=8.13, 1.13 Hz, 1 H), 7.10 (dd, J=7.75, 1.25 Hz, 1 H), 2.75 (s, 6 H).Experimental details for Compound 116Synthesis of 7-bromo-3-(2-chloro-5-(dimethylamino)phenyl)-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (Compound 116)Step-1: Synthesis of 4-chloro-N,N-dimethyl-3-nitroaniline

[0448] To a solution of 4-chloro-3-nitroaniline (2g, 11.6 mmol) in DMF (20 mL) was added sodium hydride (1.47 g, 40.5 mmol) at 0 °C and the resulting solution was stirred for 30 minutes at RT. To this reaction mixture was added methyl iodide (4.93 g, 34.8 mmol) at 0 °C. The resulting solution was stirred at RT for 16h. The progress of the reaction was monitored by TLC. After completion of stalling materials, the reaction mixture was quenched with ice and diluted with water, extracted with diethylether (3x50mL), The combined organic layer was washed with cold water (3x50 mL) and concentrated to get crude product which was carry forwarded to next step without any further purification 4-chloro-N,N-dimethyl-3-nitroaniline (1.9 g, 9.47 mmol) 82% as a pale yellow solid.Step-2: Synthesis of 4-chloro-N1,N1-dimethylbenzene-l,3-diamine

[0449] To a stirred solution of 4-chloro-N,N-dimethyl-3-nitroaniline (1.9 g, 9.47 mmol) in methanol (20 mL) and water (10 mL) were added Fe(2.6 g,46.9 mmol) and ammonium chloride (5.06 g, 94.6 mmol) at 0 °C and the resulting reaction mixtue was stirred for 2 h at 60 °C, The progress of the reaction was monitored by TLC. After 16 h the reaction mixture was filtered in hot condition, filtrate was cooled to 0 °C, the formed solid was filtered and washed with methanol and water mixture (4:1) to afford 4-chloro-N1,N1-dimethylbenzene-l,3-diamine (1.38 g, 8.14 mol, 86%) as an off white solid.

[0450] 1H NMR (400 MHz, DMSO-d6) δ 6.93 (d, J=8.76 Hz, 1 H) 6.15 (d, J=2.88 Hz, 1 H) 5.99 (dd, J=8.82, 2.94 Hz, 1 H) 5.01 (s, 2 H) 2.80 (s, 6 H); LC-MS: 94.76% at 1.06 min; m / z 171.1 [M+H] [Column: EVO C- 18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 2.5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradient)] ;Step-3: Synthesis of Compound 116

[0451] 4-chloro-N 1 ,N 1 -dimethylbenzene- 1,3-diamine (124 mg, 0.73 mmol) was dissolved in pyridine(5 mL) and to this was added 4-bromo-2-isothiocyanatobenzoate (200 mg, 0.73 mmol), the resulting mixture was stirred for 16h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reducedpressure to get crude product which was purified by combi flash column chromatography using 15-20% EtOAc in heptane as eluent to afford Compound 116 (60 mg, 0.15 mmol) as pale brown solid Yield 20%.

[0452] 1H NMR (400 MHz, DMSO-d6) δ 13.14 (s, 1 H) 7.88 (d, J=8.38 Hz, 1 H) 7.63 (d, J=1.63 Hz, 1 H) 7.53 (dd, 1=8.44, 1.81 Hz, 1 H) 7.34 (d, 1=8.88 Hz, 1 H) 6.83 (d, 1=3.00 Hz, 1 H) 6.77 (dd, 1=8.94, 3.06 Hz, 1 H) 2.90 (s, 6 H); LC-MS: 94.89% at 2.88 min; m / z 409.8 [M+H] [Column: EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase- B: ACN, Flow rate: 0.8 mL / min(Gradient)] ; HPLC: 97.58% at 9.8 min [Column: XSELECT CSH Cl 8 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 117Synthesis of 3-(2-chlorophenyl)-7-propoxy-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 117)Step-1: Synthesis of 3-(2-chlorophenyl)-7-fhioro-2-thioxo-2,3-dihydroquinazolin-4(lH)-one

[0453] To a stirred solution of 4-flouro-2-aminobenzoicacid (1 g, 6.45 mmol) and triethylamine (2.69 mL, 19.35 mmol) in t-butanol (15 mL) was added 2- chlorophenylisothiocyanate (1.2 g, 7.1 mmol) at room temperature and the resulting reaction mixture was stirred at 80°C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting material, the reaction mixture was concentrated to get crude product which was purified by combi flash column chromatography using 08% EtOAc in heptane as eluent to afford 3-(2-chlorophenyl)-7-fluoro-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (1.2 g, 3.92 mmol) as an off white solid. Yield 60%(DPC-QNZ-018)

[0454] 1H NMR (400 MHz, DMSO-d6) δ 13.25 (br s, 1 H) 8.05 (dd, J=8.74, 6.05 Hz, 1 H) 7.57 - 7.66 (m, 1 H) 7.43 - 7.52 (m, 3 H) 7.10 - 7.29 (m, 2 H); LC-MS: 98.62% at 2.58 min; m / z 304.9 [M-H] [Column: EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phasc-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradient)]; HPLC: 97.43% at 8.98 min [Column:XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Step-2: Synthesis of 3-(2-chlorophenyl)-7-propoxy-2-thioxo-2,3-dihydroquinazolin-4(lH)- one (Compound 117)

[0455] To a stirred solution of propanol (140 mg, 2.33 mmol) in DMSO (10 mL) was added potassium hydroxide (182 mg, 3.24 mmol) at RT and the resulting solution was stirred at 80 °C for Ih. To this reaction mixture was added 3-(2-chlorophenyl)-7-fluoro-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (300 mg, 0.97 mmol) at same temperature. The resulting solution was stirred for 16h at 80°C. The progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was quenched with ice and diluted with water, extracted with EtOAc (3x50mL), the combined organic layer was washed with cold water (2 x40mL) and concentrated to get crude product which was purified by column chromatography using 8% EtOAc in heptane as eluent to afford Compound 117 (100 mg, 0.29 mmol) as a white solid. Yield:30%.

[0456] 1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1 H) 7.88 (d, J=8.88 Hz, 1 H) 7.57 - 7.64 (m, 1 H) 7.43 - 7.49 (m, 3 H) 6.96 (dd, J=8.82, 2.31 Hz, 1 H) 6.92 (d, J=2.25 Hz, 1 H) 4.05 (t, J=6.50 Hz, 2 H) 1.79 (q, J=6.75 Hz, 2 H) 1.00 (t, J=7.38 Hz, 3 H); LC-MS: 92.11% at 2.90 min; m / z, 347.1 [M+H] [Column: Kinetex EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN, Flow rate: 0.8 mL / min(Gradient)]; HPLC: 96.95% at 11.72 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 118

[0457] Step-1: To a solution of methyl 5-hydroxy-2-nitrobenzoate (700 mg, 3.55) in DMF (5 mL), K2CO3(980 mg, 7.10 mmol) and 1 -bromopropane (873 mg, 7.10 mmol) were added slowly, and the resultant reaction mixture was stirred at 70 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of stalling materials, the reaction mixture was diluted with ice cold water (100 mL) and the obtained solid was filtered and residue was purified by column chromatography to afford methyl 2-nitro-5-propoxybenzoate (250 mg, 1.04 mmol, 41%).

[0458] LC-MS: 99.78% at2.84 min; m / z 240.10 [M+H]+[Column:Kinetex EVO-C18(3.0X50 mm, 2.6μm) Mobile Phase-A: 0.025%Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5 Flow rate: 0.8 mL / min(Gradient)]

[0459] Step-2: To a solution of methyl 2-nitro-5-propoxybenzoate (250 mg, 1.04 mmol) in methanol (10 mL) and water (5 mL) were added iron (287 mg, 5.23 mmol) and ammonium chloride (551 mg, 10.40 mmol) at rt and the reaction mixture was stirred at 80 °C for 3h. Progress of the reaction was monitored by TLC. After completion of starting materials, reaction mixture was cooled to RT and filtered through cclitc bed and washed with ethyl acetate. Filtrate was washed with water and concentrated under reduced pressure to afford pale brown liquid which was triturated with hexane to afford methyl 2-amino-5-propoxybenzoate (150 mg, 0.71 mmol, 69%).

[0460] LC-MS: 93.98% at 2.84 min; m / z 210.10 [M+H]+[Column :Kinetex EVO-C 18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.025% Formic acid, Mobile Phase-B: ACN T / B%: 0.01 / 5,3 / 90,5 / 90,5.5 / 5,6 / 5, Flow rate: 0.8 mL / min(Gradient)]

[0461] Step-3: methyl 2-amino-5-propoxybenzoate (150 mg, 0.71 mmol) was dissolved in pyridine (5 mL) and to this was added l-chloro-2-isothiocyanatobenzene (133 mg, 0.78 mmol), the resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starting materials, reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography to afford Compound 118 (70 mg, 0.20 mmol, 28%).

[0462] LC-MS: 95.17 % at 3.04 min; m / z 346.90 [M+H]+[Column :KINETEX EVO C18(5 cmX3.0 mm, 2.6 μ) Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN; Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN T / B%:0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 ] Flow rate: 1.2 mL / min(Gradient)] HPLC: 98.39 % at 10.22 min [Column:XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 5 mM Ammonium Bicarbonate Mobile Phase-B: ACN Program T / B%: 0.01 / 20, 12 / 90,16 / 90, Flow: 1.0mL / minute. Diluent: ACN:Water (80:20)]1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1 H) 7.91 (d, J=8.88 Hz, 1 H) 7.57 - 7.65 (m, 5 H) 7.43 - 7.49 (m, 1 H), 4.05 (t, J=6.50 Hz, 2 H) 1.83 (q, J=6.75 Hz, 2 H) 1.02 (t, J=7.38 Hz, 3 H).Experimental details for Compound 119

[0463] Step-1: To a solution of methyl 5-hydroxy-2-nitrobenzoate (5 g, 25.38 mmol) in THF (50 mL), 2-bromoethan-l-ol (3.14 g, 25.38), TPP (9.97 g, 38.07 mmol) and DIAD (7.69 g, 38.07 mmol) were added slowly at 0 °C and the resultant reaction mixture was stirred at room temperature for 2 h. Progress of the reaction was monitored by TLC. After completion of stalling materials, the reaction mixture was diluted with ice cold water (200 mL) and extracted with ethyl acetate (2x100 mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford methyl 5-(2- bromoethoxy)-2-nitrobenzoate (3 g, 9.86 mmol, 38%).

[0464] 1H NMR (400 MHz, CDC13) δ 8.12 - 8.01 (m, 1 H), 7.02 - 7.12 (m, 2 H), 4.31 - 4.39 (m, 2 H), 3.91 (s, 3 H), 3.61 - 3.72 (m, 2 H).

[0465] Step-2: To a solution of methyl 5-(2-bromoethoxy)-2-nitrobenzoate (3 g, 9.86) in ACN (30 mL), K2CO3(2.71 g, 19.72 mmol) and SM-3 (986 mg, 9.86 mmol)) were added slowly and the resultant reaction mixture was stirred at 70 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was diluted with ice cold water (100 mL) and the obtained solid was filtered and purified by column chromatography to afford methyl 5-(2-(4-methylpiperazin-l-yl)ethoxy)-2-nitrobenzoate (2 g, 6.19 mmol, 62%).

[0466] LC-MS: 97.73 % at 1.59 min; m / z 324.1 [M+H]+[Column :KINETEX EVO C18(5 cmX3.0 mm, 2.6 μ) Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN, T / B %:0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2, Flow rate: 1.2 mL / min (Gradient)].

[0467] Step-3: To a solution of methyl 5-(2-(4-methylpiperazin-l-yl)ethoxy)-2-nitrobenzoate (2 g, 6.19 mmol) in methanol (20 mL) and water (5 mL) were added iron (1.71 g, 30.95 mmol) and ammonium chloride (3.28 g, 61.90 mmol) at rt and the reaction mixture was stirred at 80 °C for 3 h. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was cooled to RT and filtered through celite bed and washed with ethyl acetate. Filtrate was washed with water and concentrated to afford pale brown liquid which was triturated with hexane to afford methyl 2-amino-5-(2-(4-methylpiperazin-l-yl)ethoxy)benzoate (1 g, 3.41 mmol, 55%).

[0468] LC-MS: 74.83 % at 0.64 min; m / z 294.1 [M+H]+[Column :KINETEX EVO C18(5 cmX3.0 mm, 2.6 μ) Mobile Phasc-A: 0.5 mL formic acid in 950 mL water in Watcr+50 mL ACN Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN, T / B %:0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Elow rate: 1.2 mL / min (Gradient)].

[0469] Step-4: methyl 2-amino-5-(2-(4-methylpiperazin-l-yl)ethoxy)benzoate (500 mg, 1.70 mmol) was dissolved in pyridine (5 mL) and to this was added SM-3 (317 mg, 1.87 mmol), the resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starting material, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography to afford Compound 119 (100 mg, 0.23 mmol, 13%).

[0470] LC-MS: 97.33 % at 1.75 min; m / z 430.09 [M+H]+[Column :KINETEX EVO C18(5 cmX3.0 mm, 2.6 μ) Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN T / B%:0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 ] Plow rate: 1.2 mL / min(Gradient)] HPLC: 97.41 % at 7.62 min [Column:XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ)Mobile Phase-A: 5 mM Ammonium BiCarbonate; Mobile Phase-B: ACN Program T / B%: 0.01 / 20, 12 / 90,16 / 90 Plow: 1.0 mL / minute. Diluent: ACN:Water (80:20)].1H NMR (400 MHz, DMSO-d6) δ 12.67 - 13.41 (m, 1 H), 7.59 - 7.63 (m, 1 H), 7.38 - 7.49 (m, 6 H), 4.11 - 4.19 (m, 2 H), 2.71 (t, J=5.13 Hz, 2 H), 2.31 - 2.48 (m, 8 H), 2.17 - 2.26 (m, 3 H).Experimental details for Compounds 120 and 121Step-1: Synthesis of methyl 5-(2-((tert-butoxycarbonyl)amino)ethoxy)-2-nitrobenzoate

[0471] To a stirred solution of methyl 5-hydroxy-2-nitrobenzoate (2 g, 10.1 mmol) in THF were added tert-butyl (2-hydroxyethyl)carbamate (2.45g, 15.2 mmol), Triphenyl phosphine (3.98 g, 15.2 mmol) and Diisopropyl azodicarboxylate (3.07 g, 15.2 mmol) at room temperature and the resulting reaction mixture was stirred at room temperature for 3 h. Progress of the reaction was monitored by TLC. After completion of starting material, the reaction mixture was concentrated to get crude product which was purified by combi flash column chromatography using 12-15% EtOAc in heptane as eluent to afford methyl 5-(2-((tert-butoxycarbonyl)amino)ethoxy)-2- nitrobenzoate 3.5 g (Impure with DIAD impurity), as brown liquid.

[0472] 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J=9.01 Hz, 1 H) 6.98 - 7.10 (m, 2 H) 6.31 (br s, 1 H) 4.07 - 4.18 (m, 2 H) 3.93 (s, 3 H) 3.57 (q, J=5.17 Hz, 2 H) 1.45 (s, 9 H); LC-MS: 99.59% at 2.71 min; m / z 363.0 [M+Na] [Column: KINETEX EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN, Flow rate: 1 .2 mL / min(Gradient)];Step-2: Synthesis of methyl 2-amino-5-(2-((tert-butoxycarbonyl)amino)ethoxy)benzoate

[0473] To a stirred solution of methyl 5-(2-((tert-butoxycarbonyl)amino)ethoxy)-2- nitrobenzoate (Impure with DIAD impurirty) (3.5 g, 10.2 mmol) in methanol (50 mL) and water(25 mL) was added Fe (2.87 g, 51 mmol) and ammonium chloride (5.61 g, 102 mmol) at RT and the resulting reaction mixtue was stirred for 2 h at 60 °C, The progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was filtered through celite bed, washed with CH2CI2(2 x 100 mL), filtrate was washed with water (50 mL), brine (50 mL) and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain methyl 2-amino-5-(2-((tert-butoxycarbonyl)amino)ethoxy)benzoate 3 g (Impure with DIAD impurity) as pale brown liquid.

[0474] 1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1 H) 7.18 (d, J=3.00 Hz, 1 H) 6.91 - 7.01 (m, 1 H) 6.73 (d, J=9.01 Hz, 1 H) 6.28 (s, 2 H) 3.83 (t, J=5.82 Hz, 2 H) 3.78 (s, 3 H) 3.23 (q, J=5.80 Hz, 2 H) 1.38 (s, 9 H); LC-MS: 99.81% at 2.67 min; m / z 333.1 [M+Na] [Column: KINETEX EVO C-18 (50x3.0 mm, 2.6μm), Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN, Flow rate: 1.2 in L / m i n( Gradient ) ] ;Step-3: Synthesis of tert-butyl (2-((3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazolin-6-yl)oxy)ethyl)carbamate

[0475] To a stirred solution of methyl 2-amino-5-(2-((tert- butoxycarbonyl)amino)ethoxy)benzoate (3 g, 9.66 mmol) in pyridine (20 mL) was added 1- chloro-2-isothiocyanatobenzene (1.63 g, 9.66 mmol), the resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography using 20- 25% EtOAc in heptane as eluent to afford product as gummy liquid which triturated with Et2O to afford tert-butyl(2-((3-(2- chlorophenyl)-4-oxo-2-thioxo-l,2,3,4-tetrahydroquinazolin-6-yl)oxy)ethyl) carbamate (2 g, 4.46 mmol) as a pale brown solid.Yiled 46%.

[0476] 1H NMR (400 MHz, CDCI3) δ 10.37 (s, 1 H) 7.53 - 7.61 (m, 2 H) 7.43 - 7.48 (m, 2 H) 7.32 - 7.37 (m, 1 H) 7.29 (dd, J=8.88, 2.88 Hz, 1 H) 7.13 (d, J=8.88 Hz, 1 H) 4.94 (br s, 1 H) 4.08 (t, J=5.07 Hz, 2 H) 3.56 (br d, J=4.63 Hz, 2 H) 1.57 (s, 9 H); LC-MS: 99.21% at 2.44 min; m / z 448.0 [M+H] [Column: KINETEX EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN, Flow rate: 1.2 mL / min(Gradient)] ;Step-4: Synthesis of 6-(2-ammoethoxy)-3-(2-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one

[0477] To a stirred solution of tert-butyl(2-((3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazolin-6-yl)oxy)ethyl)carbamate (2 g, 4.46 mmol) in CH2CI2(50 mL) was added trifluoro acetic acid (1.7 mL, 22.3 mmol) at 0 °C. The resulting reaction mixture was stirred for 16 h at RT. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was washed with Et2O and the obtained solids were filtered, dried under vacuum to afford 6-(2- aminoethoxy)-3-(2-chlorophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (1.5 g, 4.32 mmol) as a white solid. Yield:96%.

[0478] 1H NMR (400 MHz, DMSO-d6) δ 7.53 - 7.62 (m, 1 H) 7.29 - 7.50 (m, 6 H) 5.43 - 6.41 (m, 2 H) 3.96 - 4.11 (m, 2 H) 2.96 (br t, J=5.50 Hz, 2 H); LC-MS: 99.95% at 1.66 min; m / z 346.0 [M-H] [Column: KINETEX EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Watcr+50 mL ACN, Mobile Phasc-B: 0.5 mL formic acid in 1000 mL in ACN, Flow rate: 1.2 mL / min(Gradient)];Step-5: Synthesis of Compound 120

[0479] To a stirred solution of 6-(2-aminoethoxy)-3-(2-chlorophenyl)-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (1.5 g, 4.32 mmol) in Toluene(20 mL) were added iodine(1.09 g, 4.31 mmol), SM-8(1.19 g, 4.31 mmol), Et3N(0.7 mL, 8.62 mmol) at room temperature and the resulting reaction mixture was stirred at room temperature for 16 h. Progress of the reaction was monitored by TLC. After completion of starting material, the reaction mixture was diluted with EtOAc (100 mL) and washed with water (20 mL), brine (20 mL) and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to get crude product which was purified by combi flash column chromatography using 20-25% EtOAc in heptane as eluent to afford Compound 120 (900 mg, 1.52 mmol) as a pale brown solid. Yield: 35%.

[0480] 1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1 H) 11.47 (s, 1 H) 8.51 (t, J=5.44 Hz, 1 H) 7.59 - 7.64 (m, 1 H) 7.51 - 7.56 (m, 1 H) 7.42 - 7.49 (m, 4 H) 7.40 (d, J=2.88 Hz, 1 H) 4.18- 4.20 (m, 2 H) 3.69 (q, J=5.67 Hz, 2 H) 1.47 (s, 9 H) 1.39 (s, 9 H); LC-MS: 98.34% at 2.31 min; m / z 590.2 [M+H] [Column: KINETEX EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in1000 mL in ACN, Flow rate: 1.2 mL / min(Gradient)] ;Step-6: Synthesis of l-(2-((3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazolin-6-yl)oxy)ethyl)guanidine. (Compound 121)

[0481] To a stirred solution of Compound 120 (400 mg, 0.67 mmol) in CH2CI2was added trifluoro acetic acid (0.51 mL, 6.7 mmol, 10 eq) at 0 °C Resulting reaction mixture was stirred for 16 h at room temperature. Progress of the reaction was monitored by LCMS. After completion of starting material, reaction mixture was concentrated to obtain crude compound, which was triturated with CH2CI2and Et2O to afford l-(2-((3-(2-chlorophenyl)-4-oxo-2-thioxo-l, 2,3,4- tetrahydroquinazolin-6-yl)oxy)ethyl)guanidine. (Compound 121) (95 mg, 0.23 mmol) as a white solid. Yield:36%.

[0482] 1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1 H) 7.58 - 7.71 (m, 2 H) 7.37 - 7.52 (m, 6 H) 6.93 - 7.35 (m, 3 H) 4.12 - 4.22 (m, 2 H) 3.51 - 3.58 (m, 2 H); LC-MS: 97.41% at 1.23 min; m / z 390.0 [M+H] [Column: Kinetex EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradicnt)]; HPLC: 98.83% at 7.66 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium bicarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 122Synthesis of 7-bromo-3-(2-(methylamino)phenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 122)

[0483] N^methylbenzene-l^-diamine (134 mg, 1.10 mmol) was dissolved in ethanol (10 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (300 mg, 1.10 mmol), the resulting mixture was stirred for 16h at 80°C. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by Preparative HPLC to afford Compound 122 (70 mg, 0.19 mmol) as a yellow solid. Yield :17%.

[0484] 1H NMR (400 MHz, DMSO-d6) δ 12.90 (br s, 1 H) 7.82 (d, J=8.38 Hz, 1 H) 7.59 (d, J=1.75 Hz, 1 H) 7.47 (dd, J=8.44, 1.81 Hz, 1 H) 7.13 - 7.22 (m, 1 H) 6.90 (dd, J=7.57, 1.44 Hz, 1H) 6.53 - 6.61 (m, 2 H) 2.62 (d, J=4.88 Hz, 3 H); LC-MS: 99.58% at 2.07 min; m / z 363.1 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 99.82% at 9.21 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium BiCarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 123Synthesis of 7-bromo-3-(2-morpholinophenyl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 123)

[0485] 2-Morpholinoaniline (196 mg, 1.10 mmol) was dissolved in pyridine (10 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (Common inteimediate) (300 mg, 1.10 mmol), resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of stalling materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography using 15-20% EtOAc in heptane as eluent to afford Compound 123 (190 mg, 0.45 mmol) as pale brown solid. Yield: 40%.

[0486] 1H NMR (400 MHz, DMSO-d6) δ 13.07 (s, 1 H) 7.89 (d, J=8.50 Hz, 1 H) 7.64 (d, J=1.63 Hz, 1 H) 7.53 (dd, J=8.38, 1.63 Hz, 1 H) 7.39 - 7.45 (m, 1 H) 7.33 - 7.38 (m, 1 H) 7.19 - 7.31 (m, 2 H) 3.39 (t, J=4.44 Hz, 4 H) 2.83 - 2.92 (m, 2 H) 2.63 - 2.72 (m, 2 H); LC-MS: 99.81% at 1.90 min; m / z 419.1 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase- A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 99.79% at 9.64 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium BiCarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 124Synthesis of 7-bromo-3-(2-chloro-5-(trifhioromethyl)phenyl)-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (Compound 124)

[0487] 2-Chloro-5-(lri fluoromethyl Janil inc (300 mg, 1.34 mmol) was dissolved in pyridine(10 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (308 mg, 1.29 mmol), the resulting mixture was stirred for 16h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography using 15-18% EtOAc in hexane as eluent to afford Compound 124 (180 mg, 0.41 mmol) as white solid. Yield: 31%.

[0488] 1H NMR (400 MHz, DMSO-d6) δ 13.34 (s, 1 H) 8.06 (s, 1 H) 7.83 - 7.96 (m, 3 H) 7.65 (d, J=1.59 Hz, 1 H) 7.57 (dd, J=8.44, 1.59 Hz, 1 H); LC-MS: 99.44% at 2.29 min; m / z 434.9 [M-H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 99.72% at 11.05 min [Column: XSELECT CSH T3 C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium Bicarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 125Synthesis of 2-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-N- methylbenzenesulfonamide (Compound 125)

[0489] 2-Amino-N-methylbenzenesulfonamide (204 mg, 1.10 mmol) was dissolved in pyridine (10 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (300 mg, 1.10 mmol), the resulting mixture was stirred for 16h at 80°C. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography using 20-25% EtOAc in heptane as eluent to afford Compound 125 (180 mg, 0.42 mmol) as a pale brown solid. Yield: 38%

[0490] 1H NMR (400 MHz, DMSO-d6) δ 13.07 (br s, 1 H) 7.84 - 7.97 (m, 2 H) 7.59 - 7.78 (m, 3 H) 7.41 - 7.56 (m, 3 H) 2.39 (br d, J=4.38 Hz, 3 H); LC-MS: 95.61% at 1.96 min; m / z 424.0 [M-H] [Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 94.71% at 8.82 min [Column: XSELECT CSH T3 C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 126Synthesis of 2-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-N,N- dimethylbenzenesulfonamide (Compound 126)

[0491] 2-Amino-N,N-dimethylbenzenesulfonamide (220 mg, 1.10 mmol) was dissolved in pyridine(10 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (300 mg, 1.10 mmol), the resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After completion of starling materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound which was purified by combi flash column chromatography using 25-28% EtOAc in heptane as eluent to afford Compound 126 (160 mg, 0.36 mmol) as pale brown solid. Yield :32%.

[0492] 1H NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1 H) 7.84 - 7.91 (m, 2 H) 7.75 - 7.82 (m, 1 H) 7.64 - 7.70 (m, 1 H) 7.63 (d, J=1.50 Hz, 1 H) 7.49 - 7.57 (m, 2 H) 2.69 (s, 6 H); LC-MS: 91.15% at 2.05 min; m / z 440.0 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 97.98% at 8.66 min [Column: XSELECT CSH T3 C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium acetate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 127

[0493] Methyl 4-bromo-2-isothiocyanatobenzoate (common intermediate) (300 mg, 1.10 mmol) was dissolved in pyridine (5 mL) and to this was added cyclohexanamine (109 mg, 1.10 mmol), the resulting mixture was stirred for 16 h at 80°C. Progress of the reaction was monitored by TLC. After completion of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound which was purified by combi flash column chromatography to afford Compound 127 (80 mg, 0.23 mmol, 21%).

[0494] LC-MS: 99.93 % at 2.42 min; m / z 337.10 [M-H]+[Column: KINETEX EVO C18(3.0X50 mm, 2.6 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN,

[0495] Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2] Flow rate: 1 .2 mL / min (Gradient)] HPLC: 98.89 % at 9.59 min [Column; X SELECT CSH C18 (150X4.6 mm, 3.5 μm) Mobile Phasc-A: 5 mM Ammonium bicarbonate, Mobile Phase-B: ACN Program T / B%: 0.01 / 20,5 / 80,12 / 90,16 / 90. Flow: 1.0 mL / minute. Diluent: ACN:Water (80:20)].1H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1 H) 7.87 (br d, J=4.52 Hz, 1 H) 7.52 - 7.63 (m, 2 H) 5.67-5.75 (m, 1 H) 2.56-2.51 (m, 2 H) 1.56-1.42 (m, 5 H) 1.12-41 (m, 3 H).Experimental details for Compound 128Synthesis of 7-bromo-3-(3-chloropyridin-2-yl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 128)

[0496] To a stirred solution of 3-chloro-2-aminopyridine (139 mg, 1.09 mmol) and tricthylaminc (0.4 mL, 3.27 mmol) in t-butanol (5 mL) was added 4-bromo-2- isothiocyanatobenzoate (Common intermediate) (300 mg, 1.09 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After completion of starting material, reaction mixture was concentrated to get crude product which was purified by combi flash column chromatography using 50-60% EtOAc in heptane as eluent to afford Compound 128 (30 mg, 0.08 mmol) as white solid. Yield: 7%. TLC: 70% EtOAc / hexanes (Rf: 0.2);

[0497] 1H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1 H) 8.59 (dd, J=4.71, 1.53 Hz, 1 H) 8.20 (dd, J=8.07, 1.47 Hz, 1 H) 7.92 (d, J=8.44 Hz, 1 H) 7.52 - 7.69 (m, 3 H); LC-MS: 97.48% at 2.08 min; m / z 369.9 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)] ; HPLC: 99.83% at 10.12 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:Acetonitrile (95:05), Mobile Phase-B: Acetonitrile :0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 129Synthesis of 7-bromo-3-(3-chloropyridin-4-yl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one(Compound 129)

[0498] 3-Chloro-4-aminopyridine (SM-2) (140 mg, 1.1 mmol) was dissolved in pyridine(5 mL) and to this was added methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (300 mg, 1.1 mmol), resulting mixture was stirred for 16h at 80°C. After completion, reaction mixture was concentrated and crude compound was purified by combi flash column chromatography using 30-40% EtOAc in hexane as eluent to afford Compound 129 ((15 mg, 0.04 mmol) as white solid. Yield : 4% TLC: 70% EtOAc / hexanes (Rf: 0.4);

[0499] 1H NMR (400 MHz, DMSO-d6) δ 13.38 (s, 1 H) 8.86 (s, 1 H) 8.71 (d, J=5.13 Hz, 1 H) 7.91 (d, J=8.50 Hz, 1 H) 7.63 - 7.68 (m, 2 H) 7.57 (dd, J=8.50, 1.75 Hz, 1 H); LC-MS: 96.12% at 1.71 min; m / z 368.0 [M+H]+[Column: Kinetex EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase- A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 96.94% at 6.83 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium bicarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 130Synthesis of 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chloro-N- methylbenzamide (Compound 130)

[0500] 3-(7-Bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chlorobenzoic acid (Compound 107) (100 mg, 0.24 mmol) was dissolved in DMF (4 mL) and to this mixture were added methylamine. HCl (40 mg, 0.6 mmol), EDC.HCl (69 mg, 0.36 mmol) and DMAP (88mg, 0.72 mmol) at 0 °C and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of starting material, reaction mixture was diluted with water (40 mL). The formed solid was filtered and solid was washed with water and dried to afford Compound 130 (35 mg, 0.08 mmol) as an off white solid. Yield: 33%.

[0501] 1H NMR (400 MHz, DMSO-d6) δ 13.29 (s, 1 H) 8.57 (br d, J=4.52 Hz, 1 H) 7.86 -7.97 (m, 3 H) 7.74 (d, J=8.31 Hz, 1 H) 7.64 (d, J=1.59 Hz, 1 H) 7.55 (dd, J=8.50, 1.65 Hz, 1 H)2.79 (d, J=4.52 Hz, 3 H); LC-MS: 93.39% at 1.70 min; m / z 422.0 [M-H] [Column: KINETEXEVO Cl 8 (50x3.0 mm, 2.6 μm), Mobile Phase- A: 0.5 mL Foimic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)] ; HPLC: 96.41% at 5.45 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 5 mM Ammonium bicarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 131Synthesis of 3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chloro-N,N- dimethylbenzamide (Compound 131)

[0502] 3-(7-Bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chlorobenzoic acid (Compound 107) (120 mg, 0.29 mmol) was dissolved in DMF (5 mL) and to this mixture were added 2M dimethylamine in THF (0.36 mL, 0.72 mmol), EDC.HCl (83 mg, 0.43 mmol) and DMAP (106 mg, 0.87 mmol) at 0 °C and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of starting material, reaction mixture was diluted with water (30 mL). The formed solid was filtered and solid was washed with water and dried under vacuum to afford Compound 131 (70 mg, 0.16 mmol) as off white solid. Yield :55%.

[0503] 1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1 H) 7.90 (d, J=8.5O Hz, 1 H) 7.69 (d, J=8.25 Hz, 1 H) 7.63 (dd, J=10.26, 1.75 Hz, 2 H) 7.51-7.56 (m, 2 H) 2.96 (br d, J=18.39 Hz, 6 H); LC-MS: 95.73% at 2.02 min; m / z 438.0 [M+H] [Column: KINETEX EVO C18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradicnt)]; HPLC: 94.23% at 10.34 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase-A: 0.05% TFA:ACN (95:05), Mobile Phase-B: ACN:0.05% TFA (95:05), Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 132Synthesis of benzyl (2-(3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4- chlorobenzamido)ethyl)carbamate (Compound 132)

[0504] 3-(7-Bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chlorobenzoic acid (Compound 107) (200 mg, 0.48 mmol) was dissolved in DMF (4 mL) and to this mixture were added benzyl (2-aminoethyl)carbamate hydrochloride (122 mg, 0.53 mmol), EDC.HCl (138 mg, 0.72 mmol) and DMAP (176 mg, 1.44 mmol) at 0 °C and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of stalling material, reaction mixture was diluted with cold water (30 mL) and extracted with cold ethylacetate (2x25 mL). The combined organic layer was washed with cold water (2x20mL) and concentrated under reduced pressure to afford crude product, which was purified by column chromatography, 28-35% EtOAc in heaxane as eluent to afford Compound 132 (35 mg, 0.06 mmol) as an off white solid. Yield : 12%.

[0505] 1H NMR (400 MHz, DMSO-d6) δ 13.29 (br s, 1 H) 8.65 (br t, J=5.50 Hz, 1 H) 7.93 - 7.97 (m, 1 H) 7.90 - 7.93 (m, 1 H) 7.88 (s, 1 H) 7.74 (d, J=8.38 Hz, 1 H) 7.64 (d, J=1.75 Hz, 1 H) 7.55 (dd, J=8.50, 1.75 Hz, 1 H) 7.26 - 7.40 (m, 6 H) 5.01 (s, 2 H) 3.34 (br s, 2 H) 3.15 - 3.22 (m, 2 H); LC-MS: 96.74% at 2.12 min; m / z 587.0 [M-H] [Column: KINETEX EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 98.78% at 9.41 min [Column: X-Select CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase- A: 5 mM Ammonium bicarbonate; Mobile Phase-B: ACN; Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 133Synthesis of benzyl (3-(3-(7-bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4- chlorobenzamido)propyl)carbamate (Compound 133)

[0506] 3-(7-Bromo-4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)-4-chlorobenzoic acid (Compound 107) (300 mg, 0.73 mmol) was dissolved in DMF (4 mL) and to this mixture were added benzyl (3-aminopropyl)carbamate (173 mg, 0.80 mmol), EDC.HCl (210 mg, l.lmmol) and DMAP (267 mg, 2.19 mmol) at 0 °C and stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of starting material, the reaction mixture was diluted with cold water (30 mL) and extracted with cold ethyl acetate (2x25 mL). The combined organic layer was washed with cold water (2x20mL) and dried over anhydrous Na2SO4, filtered and concentrated to afford crude product which was purified by column chromatography using 30-35% EtOAc in hexane as eluent to afford Compound 133 (53 mg, 0.09 mmol) as white solid. Yield: 12%.

[0507] 1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1 H) 8.60 (t, J=5.56 Hz, 1 H) 7.88 - 8.00 (m, 3 H) 7.76 (d, J=8.31 Hz, 1 H) 7.66 (d, J=1.71 Hz, 1 H) 7.57 (dd, J=8.44, 1.83 Hz, 1 H) 7.31 - 7.40 (m, 6 H) 5.02 (s, 2 H) 3.29 (br d, J=6.48 Hz, 2 H) 3.08 (q, J=6.64 Hz, 2 H) 1.69 (br t, J=6.91 Hz, 2 H); LC-MS: 90.01% at 2.20 min; m / z 601.1 [M+H] [Column: KINETEX EVO C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL formic acid in 950 mL water in Water+50 mL ACN, Mobile Phase-B: 0.5 mL formic acid in 1000 mL in ACN, Flow rate: 1.2 mL / min(Gradient)] ; HPLC: 94.73% at 10.77 min [Column: X-Select CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase- A: 5 mM Ammonium acetate; Mobile Phase-B: ACN; Flow: 1.0 mL / min, Diluent: ACN:Water],Experimental details for Compound 134Synthesis of 7-bromo-3-(5-chloropyrimidin-4-yl)-2-thioxo-2,3-dihydroquinazolin-4(lH)-one (Compound 134)

[0508] To a solution of 5-chloropyrimidin-4-amine (172 mg, 1.32 mmol) in DMF(8 mL) was added methyl 4-bromo-2-isothiocyanatobenzoate (Common intermediate) (300mg, 1.10 mmol) and the resulting mixture was stirred at RT for Ih. To this mixture was added 10% aq. NaOH solution (5mL) and the RM was stirred at 50 °C for 2 h. The progress of the reaction monitored by TLC and LCMS. Reaction mixture was diluted with water (40mL) and washed with EtOAc (2x30 mL), Aqueous layer was acidified using IN HCl solution to pH-2 and the aqueous layer was extracted with EtOAc (2x40 mL). Combined organic layer was concentrated and the crude product was purified using flash column chromatography using 20-25% EtOAc in heptane afforded Compound 134 (46 mg, 0.13 mmol ) as white solid. Yield :12%. TLC: 50% EtOAc / hexanes (Rf: 0.1);

[0509] 1H NMR (400 MHz, DMSO-d6) δ 13.56 (s, 1 H) 9.26 - 9.34 (m, 2 H) 7.93 (d, J=8.50 Hz, 1 H) 7.66 (d, J=1.63 Hz, 1 H) 7.60 (dd, J=8.44, 1.81 Hz, 1 H); LC-MS: 97.52% at 1.94 min; m / z 368.8 [M+H] [Column: X-Select CHS C18 (50x3.0 mm, 2.5 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min( Gradient)]; HPLC: 97.72% at 7.98 min [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ), Mobile Phase-A: 5 mM Ammonium acetate, Mobile Phase-B: ACN:Water, Flow: 1.0 mL / min, Diluent: ACN:Water];Experimental details for Compound 135

[0510] Step-1: To a stirred solution of l-fluoro-2-nitrobenzene(5 g, 35.46 mmol) in DMSO (20 mL), K2CO3(9.78 g, 70.92 mmol) and tert-butyl piperazine- 1 -carboxylate (7.91 g, 42.55 mmol) were added slowly, and the resultant reaction mixture was stirred at 90 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water and the separated organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to obtain crude material, which was purified by column chromatography to afford tert-butyl 4-(2-nitrophenyl)piperazine-l- carboxylate (9 g, 29.31 mmol, 82%).

[0511] LC-MS: 98.59 % at 2.23 min; m / z 308.1 [M+H]+[Column; X-Select CHS C18 ( 3.0X 50 mm, 2.5 p ) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2, Flow rate: 1.2mL / min (Gradient)]

[0512] Step-2: To a stirred solution of tert-butyl 4-(2-nitrophenyl)piperazine- 1 -carboxylate (2 g, 6.51 mmol) in methanol (20 mL) and water (5 mL) were added iron (1.79 g, 32.57 mmol) and ammonium chloride (3.45 g, 65.10 mmol) at rt and the reaction mixture was stirred at 60 °C for 3 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was cooled to RT and filtered through celite bed, washed with ethyl acetate. The obtained filtrate was washed with water and concentrated to afford a pale brown liquid, which was triturated with hexane to afford tert-butyl 4-(2-aminophenyl)piperazine-l- carboxylate (1.6 g, 5.77 mmol) as a pale-yellow liquid, which was carried to next step without any further purification.

[0513] LC-MS: 95.07 % at 2.03 min; m / z 278.2 [M+H]+[Column: X-Select CHS C18(3.0X50 mm, 2.5 μ) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase- B: 0.5 mL Formic acid in ACN T / B %: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2, Flow rate: 1.2 mL / min (Gradient)]

[0514] Step-3: To a solution of tert-butyl 4-(2-aminophenyl)piperazine-l -carboxylate (380 mg, 1.37 mmol) in Pyridine (5 mL) was added arylisothiocyanate (Common intermediate) (410 mg, 1.50 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtaincrude product, which was purified by column chromatography to afford tert-butyl 4-(2-(7-bromo- 4-oxo-2-thioxo-l,4-dihydroquinazolin-3(2H)-yl)phenyl)piperazine-l -carboxylate (370 mg, 0.71 mmol, 52%).

[0515] LC-MS: 97.17 % at 2.28 min; m / z 516.9 [M-H]+[Column: X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water +50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2, Flow rate: 1.2 mL / min (Gradient)]

[0516] Step-4: To a stirred solution of tert-butyl 4-(2-(7-bromo-4-oxo-2-thioxo-l,4- dihydroquinazolin-3(2H)-yl)phenyl)piperazine-l -carboxylate (270 mg, 0.52 mmol) in DCM (5 mL) was added TFA (1 mL) at 0 °C, the resulting reaction mixture was stirred at RT for 2 h. progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was concentrated under reduced pressure to afford crude product which was triturated with Dichloromethane and pentane to afford Compound 135 (60 mg, 0.11 mmol, 27%).

[0517] LC-MS: 97.18 % at 1.43min; m / z 418.9 [M+H]+[Column:X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%:0.01 / 2, 0.2 / 2, 2.2 / 98, 3 / 98, 3.2 / 2, 4 / 2 Flow rate: 1.2 mL / min(Gradient)] HPLC: 99.78 % at 6.74 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 1) Mobile Phase-A: 5 mM Ammonium Bicarbonate, Mobile Phase-B: ACN Program T / B%: 0.01 / 20,12 / 90, 16 / 90. Flow: 1.0 mL / minute. Diluent: ACN:Water];1H NMR (400 MHz, DMSO-d6) δ 7.82 - 7.88 (m, 1 H), 7.57 (s, 1 H), 7.33 - 7.47 (m, 2 H), 7.15 - 7.28 (m, 3 H), 2.83 - 2.93 (m, 2 H), 2.61 - 2.68 (m, 2 H), 2.53 - 2.58 (m, 4 H).Experimental details for Compound 136 and 137

[0518] Step-1: To a stirred solution of 2-nitrobenzenesulfonyl chloride (1 g, 4.52 mmol) in DCM (10 mL) were added Pyridine (1 mL) and tert-butyl piperazine- 1 -carboxylate (1 g, 5.42 mmol) at 0 °C, the resulting reaction mixture was stirred at RT for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was concentrated under reduced pressure to afford crude product which was triturated with Dichloromethane and pentane to afford tert-butyl 4-((2-nitrophenyl)sulfonyl)piperazine-l- carboxylate (1.3 g, 3.50 mmol).

[0519] LC-MS: 90.27 % at 2.05 min; m / z 316.1 [M-56]+[Column:X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate:1.2 mL / min(Gradient),]

[0520] Step-2: To a stirred solution of tert-butyl 4-((2-nitrophenyl)sulfonyl)piperazine-l- carboxylate (1.3 g, 3.50 mmol) in methanol (10 mL) and water (5 mL) were added iron (963 mg, 17.52 mmol) and ammonium chloride (1.85 g, 35.00 mmol) at rt and the reaction mixture was stirred at 80 °C for 4h. After complete consumption of starting materials, the reaction mixture was cooled to RT and filtered through celite bed and washed with ethyl acetate. Filtrate was washed with water and concentrated under reduced pressure to afford pale brown liquid which was triturated with hexane to afford tert-butyl 4-((2-aminophenyl)sulfonyl)piperazine-l-carboxylate (1.1 g, 3.22 mmol, 91%).

[0521] LC-MS: 97.95 % at 2.00 min; m / z 286.0 [M-56]+[Column:X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN,Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3-2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient),]

[0522] Step-3: To a stirred solution of tert-butyl 4-((2-aminophenyl)sulfonyl)piperazine-l- carboxylate (800 mg, 2.34 mmol) in Pyridine (5 mL) was added arylisothiocyanate (Common intermediate) (593 mg, 2.58 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 136 (350 mg, 0.60 mmol, 23%).

[0523] LC-MS: 95.73 % at 2.17 min; m / z 580.9 [M-H]+[Column: X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradicnt)]

[0524] Step-4: To a stirred solution of Compound 136 (300 mg, 0.51 mmol) in DCM (5 mL) was added TFA (1 mL) at 0 °C, the resultant reaction mixture was stirred at RT for 16 h. progress of the reaction was monitored by TLC. After complete consumption of stalling materials, the reaction mixture was concentrated under reduced pressure to afford crude product, which was triturated with Dichloromethane and pentane to afford Compound 137 (110 mg, 0.23 mmol, 44%).

[0525] LC-MS: 95.03 % at 1.43 min; m / z 482.80 [M+H]+[Column:X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2

[0526] Flow rate: 1.2 mL / min(Gradient),] HPLC: 95.42% at 6.12 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95:05) Mobile Phase-B: 0.05% TFA:ACN (05:95) Program T / B%: 0.01 / 10, 12 / 90,16 / 90 Flow: 1 mL / min. Diluent: WATER:ACN];1H NMR (400 MHz, DMSO-d6) δ 7.96 (d, J=8.01, 1.04 Hz, 1 H), 7.82 - 7.90 (m, 2 H), 7.69 - 7.75 (m, 1 H), 7.65 (d, J=1.71 Hz, 1 H), 7.57 (d, J=16.93, 8.19, 1.41 Hz, 2 H), 3.26 - 3.30 (m, 4 H), 3.07 (t, J=4.89 Hz, 4 H).Experimental details for Compound 138

[0527] Step-1: To a stirred solution of 2-nitrobenzenesulfonyl chloride (500 mg, 2.26 mmol) in DCM (10 mL) were added Pyridine (1 mL) and 1 -methylpiperazine (271 mg, 2.71 mmol) at 0 °C, the resulting reaction mixture was stirred at RT for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of stalling materials, the reaction mixture was concentrated under reduced pressure to afford crude product which was triturated with Dichloromethane and pentane to afford l-methyl-4-((2-nitrophenyl)sulfonyl)piperazine (400 mg, 1.40 mmol, 62%).

[0528] LC-MS: 98.37 % at 1.12 min; m / z 287.1 [M-H]+[Column:X-BRIDGE BEH C-18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B %: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min (Gradient),]

[0529] Step-2: To a stirred solution of l-methyl-4-((2-nitrophenyl)sulfonyl)piperazine (400 mg, 1.40 mmol) in methanol (10 mL) and water (5 mL) were added iron (385 mg, 7.01 mmol) and ammonium chloride (742 mg, 14.00 mmol) at rt and the reaction mixture was stirred at 80 °C for 4h. After complete consumption of starting materials, the reaction mixture was cooled to RT and filtered through celite bed and washed with ethyl acetate. Filtrate was washed with water and concentrated under reduced pressure to afford pale brown liquid which was triturated with hexane to afford 2-((4-methylpiperazin-l-yl)sulfonyl)aniline (300 mg, 1.17 mmol, 84%).

[0530] LC-MS: 96.43 % at 1.01 min; m / z 256.1 [M+H]+[Column:X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min (Gradient)]

[0531] Step-3: To a stirred solution of 2-((4-methylpiperazin-l-yl)sulfonyl)aniline (300 mg, 1.17 mmol) in Pyridine (5 mL) was added arylisothiocyanate (Common intermediate) (318 mg, 1.17 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 138 (80 mg, 0.16 mmol) 14%).

[0532] LC-MS: 98.16 % at 1.45 min; m / z 496.8 [M+H]+[Column:X-BRIDGE BEH C- 18(3.0X50 mm, 2.5 μm) Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient)] HPLC: 99.33 % at 6.26 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 0.05% TFA:ACN (95;05) Mobile Phase-B: 0.05% TFA:ACN (05;95) Program T / B%: 0.01 / 10, 12 / 90,16 / 90 Flow: 1 mL / min. Diluent: WATER: ACN;1H NMR (400 MHz, DMSO-d6) δ 12.97 - 13.19 (m, 1 H), 7.76 - 7.94 (m, 3 H), 7.49 - 7.71 (m, 4 H), 3.05 (s, 4 H), 2.28 (s, 4 H), 2.14 (s, 3 H).Experimental details for Compound 139Synthesis of 7-bromo-3-(2-(morpholinosulfonyl)phenyl)-2-thioxo-2,3-dihydroquinazolin- 4(lH)-one (Compound 139)Step-1: Synthesis of 4-((2-nitrophenyI)sulfonyl)morpholine

[0533] To a stirred solution of morpholine (0.39 mL, 4.96 mmol) in CH2CI2(20 mL) under argon atmosphere were added pyridine (0.72 mL, 9.02 mmol) and sulfonyl chloride (1 g, 4.51 mmol) at 0 °C, warmed to room temperature and stirred for 16 h. The progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with CH2CI2(30 mL), washed with water (15 mL), IN HCl (10 mL), 10% NaHCO3solution (15 mL) and brine (15 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain 4-((2-nitrophenyl)sulfonyl)morpholine (1 g, 3.67 mmol) as a pale yellow gummy liquid. Yeild: 74%.

[0534] 1H NMR (400 MHz, DMSO-d6) δ 7.98 - 8.04 (m, 2 H) 7.84 - 7.97 (m, 2 H) 3.61 - 3.67 (m, 4 H) 3.12 - 3.18 (m, 4 H); LC-MS: 98.0% at 1.66 min; m / z 273.0 [M+H] [Column: X-BRIDGEBEH C-18 (50x3.0 mm, 2.6 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)];Step-2: Synthesis of 2-(morpholinosulfonyl)aniline

[0535] To a stirred solution of 4-((2-nitrophenyl)sulfonyl)morpholine (1 g, 3.67 mmol) in methanol (20 mL) and water (10 mL) were added Fe (1.02 g, 18.3 mmol) and ammonium chloride (1.96 g, 36.7 mmol) at RT and the resulting reaction mixtue was stirred for 2 h at 60 °C. The progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was filtered through celite bed, washed with CH2CI2(50 mL), filtrate was washed with water(20 mL), brine (20 mL) and dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to obtain 2-(morpholinosulfonyl) aniline (800 mg, 3.30 mmol) as a pale brown solid. Yield 90%.

[0536] 1H NMR (400 MHz, DMSO-d6) δ 7.27 - 7.41 (m, 2 H) 6.87 (dd, J=8.31, 0.86 Hz, 1 H) 6.60 - 6.69 (m, 1 H) 6.07 (s, 2 H) 3.53 - 3.66 (m, 4 H) 2.87 - 3.00 (m, 4 H); LC-MS: 93.25% at 1.54 min; m / z 243.0 [M+H] [Column: X-BRIDGE BEH C-18 (50x3.0 mm, 2.5 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)] ;Step-3: Synthesis of 7-bromo-3-(2-(morpholinosulfonyl)phenyl)-2-thioxo-2,3- dihydroquinazolin-4(lH)-one (Compound 139):

[0537] To a stirred solution of 2-(morpholinosulfonyl)aniline (300 mg, 1.23 mmol) in pyridine (10 mF) was added methyl 4-bromo-2-isothiocyanatobenzoate (334 mg, 1.23 mmol), resulting mixture was stirred for 16 h at 80 °C. Progress of the reaction was monitored by TLC. After complete consumption of stalling materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was purified by combi flash column chromatography using 20-25% EtOAc in heptane as eluent to afford Compound 139 (60 mg, 0.12 mmol) as an off- white solid Yield 10%.

[0538] 1H NMR (400 MHz, DMSO-d6) δ 13.14 (s, 1 H) 7.86 - 7.95 (m, 2 H) 7.81-7.85 (m, 1 H) 7.68-7.71 (m, 1 H) 7.62 (d, J=1.63 Hz, 1 H) 7.53-7.56 (m, 2 H) 3.55 (t, J=4.69 Hz, 4 H) 2.99 - 3.07 (m, 4 H); LC-MS: 96.29% at 1.83 min; m / z 481.8 [M+H] [Column: X-BRIDGE BEH C-18 (50x3.0 mm, 2.5 μm), Mobile Phase-A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: 0.5 mL Formic acid in ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 97.78% at 9.96 min [Column: XSELECT CSH C18 (150 X 4.6mm, 3.5μ), Mobile Phase-A: 0.05%TFA:ACN (95:05), Mobile Phase-B: 0.05% TFA:ACN (05:95), Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 140

[0539] To a stirred solution of 2-amino-3-bromobenzoic acid (300 mg, 1.38 mmol) and triethylamine (420 mg, 4.16 mmol) in t-Butanol (5 mL) was added l-chloro-2- isothiocyanatobcnzcnc (256 mg, 1.51 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TEC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30 mF). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 140 (100 mg, 0.27 mmol, 19%).

[0540] LC-MS: 98.72 % at 1.79 min; m / z 365.05 [M-H]+[Column : X-Bridge BEH C18 (50x3) mm 2.5u Mobile Phase- A: 2.5 mM Ammonium Bicarbonate in water, Mobile Phase-B:Acetonitrile T / B%:0.01 / 2, 0.2 / 2, 2.2 / 98, 3 / 98, 3.2 / 2, 4 / 2 Flow rate: 1.2 mL / min(Gradient),] HPLC: 98.25 % at 5.96 min [Column: X SELECT CSH C18 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 5 mm Ammonium bicarbonate; Mobile Phase-B: ACN Program T / B%: 0.01 / 20,5 / 80, 12 / 90,16 / 90 Flow: 1 mL / min. Diluent: WATER:ACN];1H NMR (500 MHz, DMSO-d6) δ 11.30 (s, 1 H), 8.13(dd, J=7.93, 1.22 Hz, 1 H), 8.02 (dd, J=7.86, 1.14 Hz, 1 H), 7.61 - 7.66 (m, 1 H), 7.47 - 7.54 (m, 3 H), 7.33 (t, J=7.86 Hz, 1 H).Experimental details for Compound 141

[0541] To a stirred solution of 2-amino-3-chlorobenzoic acid (200 mg, 1.16 mmol) and triethylamine (354 mg, 3.50 mmol) in t-Butanol (5 mL) was added l-chloro-2- isothiocyanatobenzene (215 mg, 1.27 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 141 (120 mg, 0.37 mmol, 32%).

[0542] LC-MS: 97.65 % at 1.91 min; m / z 365.05 [M-H]+[X-Select CSH C18 (3.0x50 mm, 2.5 μm), Mobile Phase-A: 0.05% Formic acid in water:ACN (95:5), Mobile Phase-B: ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient),] HPLC: 99.25 % at 7.45 min [Column: X SELECT CSH Cl 8 (150 X 4.6 mm, 3.5 μ) Mobile Phase-A: 5 mm Ammonium bicarbonate Mobile Phase-B: ACN Program T / B%: 0.01 / 20,5 / 80, 12 / 90,16 / 90, Flow: 1 mL / min. Diluent: WATER:ACN];1H NMR (400 MHz, DMSO-d6) δ 12.01 (s, 1 H), 7.97 (d, J=7.88, 6.38, 1.38 Hz, 2 H), 7.60 - 7.66 (m, 1 H), 7.45 - 7.54 (m, 3 H), 7.39 (t, J=7.94 Hz, 1 H).Experimental details for Compound 142

[0543] To a stirred solution of 2-amino-3-methoxybenzoic acid (200 mg, 1.19 mmol) and triethylamine (362 mg, 3.59 mmol) in t-Butanol (5 mL) was added l-chloro-2- isothiocyanatobenzene (221 mg, 1.30 mmol) at room temperature and the resulting reaction mixture was stirred at 80 ° C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 142 (40 mg, 0.12 mmol, 11 %).

[0544] LC-MS: 98.84 % at 1.80min; m / z 318.90 [M-H]+[X-Select CSH C18 (3.0x50 mm, 2.5 μm) Mobile Phase-A: 0.05% Formic acid in water:ACN (95:5), Mobile Phase-B: ACN, T / B%:0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient),] HPLC: 98.22 % at 9.25 min [Column: X SELECT CSH Cl 8 (150 X 4.6 mm, 3.5 μ) Mobile Phase- A: 5 mm Ammonium bicarbonate Mobile Phase-B: ACN Program T / B%: 0.01 / 20,5 / 80, 12 / 90,16 / 90 Flow: 1 mL / min. Diluent: WATER:ACN]1H NMR (500 MHz, DMSO-d6) δ 12.04 (s, 1 H), 7.59 - 7.64 (m, 1 H), 7.54 (dd, .7=8.01, 1.14 Hz, 1 H), 7.44 - 7.50 (m, 4 H), 7.31 - 7.36 (m, 1 H), 3.95 (s, 3 H).Experimental details for Compound 143

[0545] To a stirred solution of 2-amino-3-(trifluoromethyl)benzoic acid (300 mg, 1.46 mmol) and triethylamine (443 mg, 4.39 mmol) in t-Butanol (5 mL) was added l-chloro-2- isothiocyanatobenzene (271 mg, 1.60 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of stalling materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 143 (260 mg, 0.73 mmol, 50%).

[0546] LC-MS: 99.25 % at 1.49min; m / z 318.90 [M-H]+[Column: X-Select CSH-C18- 50X3.0 mm 2.5 p Mobile Phase A: 0.05% FA in water, Mobile Phase-B: ACN, T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.5 mL / min(Gradient),] HPLC: 98.73 % at 5.76 min [Column : X-Select CSH C18 (4.6x150 mm, 3.5 μ) Mobile Phase-A: 5 mM Ammonium Bicarbonate in water, Mobile Phase-B: ACN Program T / B%: 0.01 / 10, 6.0 / 90, 10.0 / 100, 12.0 / 100, 14.0 / 10, 18.0 / 10 Flow: 1 mL / min. Diluent: WATER:ACN].1H NMR (400 MHz, DMSO-d6) δ 10.99 - 11.69 (m, 1 H), 8.32 (dd, J=7.88, 1.00 Hz, 1 H), 8.17 - 8.24 (m, 1 H), 7.61 - 7.67 (m, 1 H), 7.47 - 7.59 (m, 4 H).Experimental details for Compound 144

[0547] To a stirred solution of 2-amino-6-bromobenzoic acid (500 mg, 2.31 mmol) and triethylamine (701 mg, 6.94 mmol) in t-Butanol (5 mL) was added l-chloro-2- isothiocyanatobenzene (429 mg, 2.54 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was diluted with ice cold water (50 mL) and extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 144 (60 mg, 0.16 mmol, 7%).

[0548] LC-MS: 94.07 % at 2.02 min; m / z 366.4 [M-H]+[Column : X-Bridge BEH C18 (50x3 mm, 2.5 μ), Mobile Phase-A: 2.5 mM Ammonium Bicarbonate in water, Mobile Phase-B: ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient)] HPLC: 94.07 % at 7.42 min [Column : X-Select CSH C18 (4.6x150 mm, 3.5 μ) Mobile Phase-A: 5 mM Ammonium Bicarbonate in water, Mobile Phase-B: ACN Program T / B%: 0.01 / 10, 6.0 / 90, 10.0 / 100, 12.0 / 100, 14.0 / 10, 18.0 / 10 Flow: 1 mL / min. Diluent: WATER:ACN].1H NMR (400 MHz, DMSO-d6) δ 13.22 (s, 1 H), 7.60 - 7.67 (m, 3 H), 7.45 - 7.52 (m, 4 H).Experimental details for Compound 145

[0549] To a stirred solution of 2-amino-5-chlorobenzoic acid (300 mg, 1.74 mmol) and triethylamine (0.36 mL,2.62 mmol) in ethanol (10 mL) was added 2-chloroisothiocyanate (296 mg, 1.74 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was concentrated under reduced pressure to obtain crude product,which was purified by combi flash chromatography using 15-25% EtOAc in heptane as eluent to afford Compound 145 (127 mg, 0.39 mmol) as an off-white solid Yield :22%.

[0550] 1H NMR (500 MHz, DMSO-d6) δ 13.23 (s, 1 H) 7.74 (t, J=8.09 Hz, 1 H) 7.60 - 7.64 (m, 1 H) 7.46 - 7.51 (m, 3 H) 7.40-7.44 (m, 2 H); LC-MS: 99.72% at 1.89 min; m / z 324.7 [M+H]+[Column: X-Bridge BEH C18 (50x3.0 mm, 2.5 μm), Mobile Phase- A: 2.5 mM Ammonium Bicarbonate in water, Mobile Phase-B: ACN, Inj Volume: 2μL, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 98.98% at 9.04 min [Column: XSELECT CSH C18 (150 X 4.6 mm, 3.5 μ), Mobile Phase- A: 5 mM Ammonium bicarbonate, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 146

[0551] To a stirred solution of 2-amino-6-(trifhioromethyl)benzoic acid (150 mg, 0.73 mmol) and triethylamine (221 mg, 2.19 mmol) in t-Butanol (5 mL) was added 1-chloro-2- isothiocyanatobenzene (135 mg, 0.80 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was cooled to room temperature and diluted with ice cold water (50 mL), extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtain crude product, which was purified by column chromatography to afford Compound 146 (35 mg, 0.098 mmol, 11%).

[0552] LC-MS: 99.49 % at 2.01 min; m / z 356.85 [M+H]+[Column : X-Bridge BEH C18 (50x3 mm, 2.5 μ), Mobile Phase- A: 2.5 mM Ammonium Bicarbonate in water, Mobile Phase-B: ACN T / B%: 0.01 / 2,0.2 / 2,2.2 / 98,3 / 98,3.2 / 2,4 / 2 Flow rate: 1.2 mL / min(Gradient)] HPLC: 99.61 % at 7.36 min [Column : X-Select C18 (4.6x150 mm, 3.5 μ) Mobile Phase-A: 5 mM Ammonium bicarbonate in water; Mobile Phase-B: ACN Program T / B%: 0.01 / 10, 6.0 / 90, 10.0 / 100, 12.0 / 100, 14.0 / 10, 18.0 / 10 Flow: 1 mL / min. Diluent: WATER: ACN].1H NMR (400 MHz, DMSO-d6) δ 3.37 (s, 1 H), 7.93 - 7.99 (m, 1 H), 7.78 (d, J=8.13 Hz, 2 H), 7.61 - 7.64 (m, 1 H), 7.46 - 7.52 (m, 3 H).Experimental details for Compound 147Step-1: Synthesis of tert-butyl (2-nitrophenyl)carbamate

[0553] To a stirred solution of 2-nitro aniline (2 g, 14.4 mmol) in DMF (20 mL) were added 60% NaH (1.15g, 28.8 mmol), (BoC)2O (3.63 mL, 15.84 mmol) at 0 °C and the resulting reaction mixture was stirred at room temperature for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was poured in to ice cold water and resultant aqueous layer was extracted with EtOAc (2 x 100 mL). The combined organic layer was washed with water (50 mL), brine(50 mL), dried over anhydrous Na2SO4and concentrated to afford crude tert-butyl (2-nitrophenyl)carbamate (2), the crude product was purified by column chromatography using 7-10% EtOAc in heptane as eluent to afford tert-butyl (2-nitrophenyl)carbamate, (1.8 g, 7.55 mmol) as a pale yellow liquid. Yield: 52%.

[0554] 1H NMR (400 MHz, DMSO-d6) δ 9.59 (s, 1 H) 7.95 (d, J=8.19 Hz, 1 H) 7.63 - 7.69 (m, 2 H) 7.20 - 7.34 (m, 1 H) 1.43 - 1.47 (m, 9 H).Step-2: Synthesis of tert-butyl methyl(2-nitrophenyl)carbamate

[0555] To a stirred solution of tert-butyl (2-nitrophenyl)carbamate (1.8 g, 7.55 mmol) in DMF (20 mL) were added 60% NaH (3.02 g, 75.5 mmol, 10 eq), Mel (0.7 mL, 11.3 mmol, 1.5 eq) at 0 °C and the resulting reaction mixture was stirred at room temperature for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was poured in to ice cold water and resultant aqueous layer was extracted with EtOAc (2 x 100 mL). The combined organic layer was washed with water (50 mL), brine(50 mL), dried over anhydrous Na2SO4. filtered and concentrated under reduced pressure to obtain crude product whichwas purified by column chromatography using 12-15% EtOAc in heptane as eluent to afford tertbutyl methyl(2-nitrophenyl)carbamate, (1.5 g, 5.94 mmol) as a pale yellow liquid. Yield: 78%.

[0556] 1H NMR (400 MHz, DMSO-d6) δ 7.97 (br d, J=7.95 Hz, 1 H) 7.73-7.76 (m, 1 H) 7.59 (d, J=7.34 Hz, 1 H) 7.44 - 7.55 (m, 1 H) 3.21 (s, 3 H) 1.16 - 1.45 (m, 9 H).Step-3 : Synthesis of tert-butyl (2-aminophenyl)(methyl)carbamate

[0557] To a stirred solution of tert-butyl methyl(2-nitrophenyl)carbamate (1.5 g, 5.94 mmol) in methanol (50 mL) and water (25 mL) were added Fe (1.63 g, 29.7 mmol) and ammonium chloride (3.1 g, 59.4 mmol) at RT and the resulting reaction mixtue was stirred for 2 h at 60 °C. The progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was filtered through celite bed, washed with CH2CI2(2 x 100 mL). The filtrate was washed with water (50 mL), brine (50 mL) and concentrated in vacuo to afford tert-butyl (2-aminophenyl)(methyl)carbamate (1.2 g, 5.40 mmol) as a pale brown liquid. Yield: 91%.

[0558] 1H NMR (400 MHz, DMSO-d6) δ 6.81 - 7.02 (m, 2 H) 6.69 (br d, J=7.88 Hz, 1 H) 6.50 (br t, J=7.25 Hz, 1 H) 4.84 (br s, 2 H) 2.98 (s, 3 H) 1.16 - 1.56 (m, 9 H).Step-4: Synthesis of tert-butyl methyl(2-(4-oxo-2-thioxo-7-(trifluoromethyl)-l,4- dihydroquinazolin-3(2H)-yl)phenyl)carbamate

[0559] To a stirred solution of tert-butyl (2-aminophenyl)(methyl)carbamate (450 mg, 2.02 mmol) in Pyridine (20 mL) was added methyl 2-isothiocyanato-4-(trifluoromethyl)benzoate (528 mg, 2.02 mmol) at room temperature and the resulting reaction mixture was stirred at 80 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting material, the reaction mixture was concentrated to get crude product which was purified by combi flash column chromatography eluted with 15-20% EtOAc in heptane to afford tert-butyl methyl(2- (4-oxo-2-thioxo-7-(trifluoromethyl)-l,4-dihydroquinazolin-3(2H)-yl)phenyl)carbamate (420 mg, 0.93 mmol) as a pale brown solid. Yield: 46%.

[0560] 1H NMR (400 MHz, DMSO-d6) δ 13.07 - 13.32 (m, 1 H) 8.14 (d, J=8.19 Hz, 1 H) 7.72 (s, 1 H) 7.65 (br d, J=8.19 Hz, 1 H) 7.35 - 7.51 (m, 4 H) 3.00 (br s, 3 H) 1.12 - 1.19 (m, 9 H); LC-MS: 97.74% at 2.23 min; m / z 450.2 [M-H] [Column: X-Select CSH C18 (50x3.0 mm, 2.5 μm), Mobile Phase-A: 0.05% Formic acid in water:ACN (95:05), Mobile Phase-B: ACN, Flow rate: 1.2 mL / min(Gradient)] ;Step-5: Synthesis of 3-(2-(methylamino)phenyl)-2-thioxo-7-(trifluoromethyl)-2,3- dihydroquinazolin-4(lH)-one (Compound 147).

[0561] To a stirred solution of tert-butyl methyl(2-(4-oxo-2-thioxo-7-(trifluoromethyl)-l,4- dihydroquinazolin-3(2H)-yl)phenyl)carbamate (420 mg, 0.93 mmol) in MeOH (10 mL) was added 4M HCl in 1,4-Dioxane (5 mL) at 0 °C. The resulting mixture was stirred for 16 h at RT. Progress of the reaction was monitored by LCMS. After complete consumption of stalling materials, the reaction mixture was concentrated under reduced pressure to obtain crude compound, which was washed with CH2CI2and Et2O to afford 3-(2-(methylamino)phenyl)-2- thioxo-7-(trifluoromethyl)-2,3-dihydroquinazolin-4(lH)-one (Compound 147). (120 mg, 0.34 mmol) as a white solid. Yield: 36%

[0562] 1H NMR (400 MHz, DMSO-d6) δ 13.06 (s, 1 H) 8.11 (d, J=8.25 Hz, 1 H) 7.73 (s, 1 H) 7.62 (dd, J=8.25, 1.13 Hz, 1 H) 7.12 - 7.28 (m, 1 H) 6.93 (dd, J=7.63, 1.38 Hz, 1 H) 6.47 - 6.71 (m, 2 H) 5.60 (q, J=4.63 Hz, 1 H) 2.63 (d, J=4.75 Hz, 3 H); LC-MS: 99.03% at 2.05 min; m / z 352.2 [M+H] [Column: X-BRIDGE BEH C-18 (50x3.0 mm, 2.5 μm), Mobile Phase- A: 0.5 mL Formic acid in 950 mL water+50 mL ACN, Mobile Phase-B: ACN, Flow rate: 1.2 mL / min(Gradient)]; HPLC: 94.32% at 8.45 min [Column: X-Bridge C18 (150 X 4.6 mm, 5 μ), Mobile Phase-A: 5 mM Ammonium Bicarbonate in water, Mobile Phase-B: ACN, Flow: 1.0 mL / min, Diluent: ACN: Water];Experimental details for Compound 148

[0563] To a stirred solution of 2-isothiocyanato-4-(trifluoromethyl)benzoic acid (300 mg, 1.14 mmol) in Pyridine (5 mL) was added 2-morpholinoaniline (245 mg, 1.37 mmol) at room temperature and the resulting reaction mixture was stirred at 90 °C for 16 h. Progress of the reaction was monitored by TLC. After complete consumption of starting materials, the reaction mixture was cooled to room temperature and diluted with ice cold water (50 mL), extracted with ethyl acetate (2x30 mL). The combined organic layer was concentrated under reduced pressure to obtaincrude product, which was purified by column chromatography to afford Compound 148 (140 mg, 0.42 mmol, 30%).

[0564] LC-MS: 99.32 % at 1.40 min; m / z 408.40 [M+H]+[Column : X-Select CSH C18 (3.0x50 mm, 2.5 μm), Mobile Phase-A: 0.05% Formic acid in water:ACN (95:05), Mobile Phase- B: ACN T / B%: 0.0 / 0, 1.5 / 100, 2.2 / 100, 2.6 / 0, 3 / 0, Flow rate: 1.2 mL / min(Gradient)] HPLC: 95.285 % at 7.50 min [Column : X-Select CSH C18 (4.6x150 mm, 3.5 μ) Mobile Phase-A: 5 mM Ammonium Bicarbonate in water, Mobile Phase-B: ACN Program T / B%: 0.01 / 10, 6.0 / 90, 10.0 / 100, 12.0 / 100, 14.0 / 10, 18.0 / 10 Flow: 1 mL / min. Di...

Claims

CLAIMS1. A compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein:X1is S, O, NRc;R1is -C1-4alkylC(O)OH, -C1-4alkylC(O)OC1-4alkyl, -OC1-4alkyleneC(O)OC1-4alkyl, -C1-4alkylC(O)NRcRd,R2is, SC1-6alkyl, SC1-4alkylene, SC1-4alkylR13, SC1-4alkylN(Ra)(Rb), or =S;R13is selected from the group consisting of hydrogen, halogen, OH, C(O)OH, - C(O)NRcRd, C(O)OC1-4alkyl, cyclohexyl, morpholinyl, phenyl, indole, pyrrolidine, pyridyl ;R3is absent or hydrogen;Raand Rbare independently selected from the group consisting of hydrogen, CN, C1-4alkyl and C2-4alkenyl; each ofR4, R5, R6, and R7is independently selected from the group consisting of hydrogen, halogen, NO2, CN, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, OC1-4alkylene-R14, guanidinyl and R16;R14is independently selected for each occurrence from the group consisting of hydrogen,CN, OH, NRcRd, C1-4alkyl, C(O)OH, C(O)OC1-4alkyl, OC1-4alkyl, C(O)NRcRd, OC(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo;R8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C1-4alkyl, C1-4haloalkyl, NHC(O)C1-4alkyl, OC1-4alkyl, C(O)OH, C(O)OC1-4alkyl, C(O)NRcRd, S(O)qNRcRd, NHC(O)NRcRd, guanidinyl, NHCN(C(O)O- tertbutyl)N(H)C(O)O-tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;R18is hydrogen, C1-4alkyl, C(O)OC1-4alkyl or S(O)qNRcRd;Rcand Rdare independently selected for each occurrence from the group consisting of hydrogen, C1-4alkyl, C1-4haloalkyl C3-6monocycloalkyl, and C(O)OC1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein3. The compound of claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, S(O)qC1-4alkyl, OC1-4alkyl-R14, and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, C(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo.

4. The compound of any of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein two of R4, R5, R6, and R7are hydrogen.

5. The compound of any of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein three of R4, R5, R6, and R7are hydrogen.

6. The compound any of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are halo.

7. The compound of any of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are Br.

8. The compound of any of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are OC1-4alkyl-R14.

9. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are -OCH3.

10. The compound according to any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R3is H.

11. The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein R3is absent.

12. The compound of any of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein R1is13. The compound of any of claims 1 to 12, or a pharmaceutically acceptable salt thereof, wherein three of R8, R9, R10, R11and R12are hydrogen.

14. The compound of any of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein four of R8, R9, R10, R11and R12are hydrogen.

15. The compound of any of claims 1 to 14, or a pharmaceutically acceptable salt thereof, wherein one of R8, R9, R10, R11and R12are halo.

16. The compound of any of claims 1 to 15, or a pharmaceutically acceptable salt thereof, wherein one of R8, R9, R10, R11and R12are Cl.

17. A compound of Formula IIor a pharmaceutically acceptable salt thereof, wherein:X1is S, O, NRc;R1is -C1-4alkylC(O)OH, -C1-4alkylC(O)OC1-4alkyl, -OC1-4alkyleneC(O)OC1-4alkyl, -C1-4alkylC(O)NRcRd,R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, CN, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, OC1-4alkylene-R14, guanidinyl and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, NRcRd, C1-4alkyl, C(O)OH, C(O)OC1-4alkyl, OC1-4alkyl, C(O)NRcRd, OC(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo;R8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C1-4alkyl, C1-4haloalkyl, NHC(O)C1-4alkyl, OC1-4alkyl, C(O)OH, C(O)OC1-4alkyl, C(O)NRcRd, S(O)qNRcRd, NHC(O)NRcRd, guanidinyl, NHCN(C(O)O- tertbutyl)N(H)C(O)O-tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;R18is hydrogen, C1-4alkyl, C(O)OC1-4alkyl or S(O)qNRcRd;Rcand Rdare independently selected for each occurrence from the group consisting of hydrogen, C1-4alkyl, C1-4haloalkyl C3-6monocycloalkyl, and C(O)OC1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

18. The compound of claim 17, or a pharmaceutically acceptable salt thereof, wherein19. The compound of claims 17 or 18, or a pharmaceutically acceptable salt thereof, wherein R4, R5, R6, and R7are independently selected from the group consisting of hydrogen, halogen, NO2, OH, NRcRd, C(O)OH, C(O)NRcRd, C(O)OC1-4alkyl, OC(O)C1-4alkyl, NHC(O)C1-4alkyl, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl-R14, and R16;R14is independently selected for each occurrence from the group consisting of hydrogen, CN, OH, NRcRd, C1-4alkyl, C(O)NRcRd, guanidinyl, boc-guanidinyl, and R16; R16isReis hydrogen or halo.

20. The compound of any of claims 17 to 19, or a pharmaceutically acceptable salt thereof, wherein two of R4, R5, R6, and R7are hydrogen.

21. The compound of any of claims 17 to 20, or a pharmaceutically acceptable salt thereof, wherein three of R4, R5, R6, and R7are hydrogen.

22. The compound any of claims 17 to 21, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are halo.

23. The compound of any of claims 17 to 22, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are Br.

24. The compound of any of claims 17 to 23, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are OC1-4alkyl-R14.

25. The compound according to any one of claims 17 to 22, or a pharmaceutically acceptable salt thereof, wherein one of R4, R5, R6, and R7are -OCH3.

26. A compound of Formula III or a pharmaceutically acceptable salt thereof,whereinR8, R9, R10, R11, and R12are independently selected from the group consisting of hydrogen, halogen, NReRd, C1-4haloalkyl, C(O)NRcRd, S(O)qNRcRd, NHCN(C(O)O-tertbutyl)N(H)C(O)O- tertbutyl, -C(O)N(Rc)C1-4alkylN(Rd)R17and R17; R17isL1is a bond or -S(O)q-;Reand Rdare independently selected for each occurrence from the group consisting of hydrogen and C1-4alkyl; and q is independently selected for each occurrence from the group consisting of 0, 1 and 2.

27. A pharmaceutical composition comprising the compound according to any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

28. A method of treating Hepatitis B (HBV) infection in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof.

29. A method of treating Hepatitis B (HBV) infection in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of pharmaceutical composition of claim 25.

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