A process for the preparation (UN)substituted quinolone and isoquinolone compounds

Abstract

The present invention discloses a functionalized isoquinolone and quinolone compounds and an efficient transition-metal-free approach for the synthesis of the same. The invention provides a highly functionalized isoquinolones from the reaction of dimethyl-2-((phenylamino)methylene) malonate with aryne precursors under mild. The reaction proceeds through insertion of aryne into the C−C σ-bond, which offers a novel and practical entry to access a wide range of isoquinolones with enhanced yields. The substrate scope is broad as the process can stands a variety of functional groups and the application of the developed process has been demonstrated in the total synthesis of antimalarial agent SJ000101247. Also, the highly functionalized quinolones are also useful in the synthesis of floxacins based compounds and derivatives e.g. ciprofloxacin, norfloxacin, G003967, etc.

Description

[0001] A PROCESS FOR THE PREPARATION (UN)SUBSTITUTED QUINOLONE AND ISOQUINOLONE COMPOUNDS

[0002] FIELD OF THE INVENTION

[0003] The present invention provides a process for the preparation of (un)substituted isoquinolone compounds derivatives / analogues and salt forms of Formula I and (un)substituted quinolone, derivatives / analogues and salt forms of Formula IV. Particularly, the present invention relates to a transition-metal-free method of synthesizing isoquinolone of Formula I and quinolone of Formula IV (also be referred as “floxacin based compounds”). More particularly, present invention relates to a transition metal / heavy metal free catalytic system for production of substituted isoquinolone compounds via aryne intermediate formation which provides the desired compounds with yield in the range of 70-80%.

[0004] BACKGROUND OF THE INVENTION

[0005] Isoquinolones and quinolones are class of organic compounds characterized by bicyclic structure composed of benzene ring fused to pyridine ring. Isoquinolones, quinolones & their derivatives have demonstrated wide range of potential biological & pharmacological activities, making them valuable compounds for drug discovery & development.

[0006] For instance, isoquinolones have shown antibacterial, antifungal and antioxidant properties. Certain isoquinolones exhibit anticancer properties by interfering with the growth and proliferation of cancer cells. Isoquinolones have also been investigated for their anti-inflammatory and analgesic effects by inhibiting inflammation-related enzymes and pathways, offering potential for pain relief and treating inflammatory conditions. Isoquinolones have also been studied for their impact on the nervous system and have also been examined for their effects on the cardiovascular system, antiviral activity and antiparasitic activity. Also, broad antibacterial spectrum, high oral bioavailability and excellent tissue penetration combined with safety and few, yet rare, unwanted effects, have made the quinolones class of antimicrobials one of the most used in inpatients and outpatients. However, the biological and pharmacological activities of isoquinolones and quinolones can vary widely based on their specific chemical structures, substitutions, and mechanisms of action. The development of isoquinolone- and quinolone-based drugs involves optimizing their properties for specific therapeutic purposes while minimizing potential side effects. Researchers continue to explore and refine isoquinolone and quinolone derivatives for various medical applications.

[0007] The wide applications of isoquinolone and quinolonehave attracted the attention of organic and medicinal chemistry researchers’ worldwide.

[0008] Reference may be made to the article “Chem. Lett. 2010, 39, 744-746”, which discloses the preparation of isoquinolone and quinolone compounds using transition metal catalysts which also requires the oxidants to recycle the catalyst. However, it requires careful optimization and consideration of reaction conditions to ensure both catalyst regeneration and product yield while minimizing unwanted side reactions.

[0009] Reference may be made to the article “J. Org. Chem. 2019, 84, 12314-12323” which discloses the synthesis of isoquinolone from aromatic amide, where amide nitrogen contains a directing group which help to bind the metal catalyst. However, the process will not be efficient in absence of the directing group and metal catalyst.

[0010] Reference may be made to the patent document CA2905089C, which discloses a compound and a composition comprising an isoquinoline compound and a prostaglandin or a prostaglandin analog, where the isoquinoline compound is covalently linked to a prostaglandin or a prostaglandin analog to treat the ocular diseases.

[0011] Reference may be made to the article “Molecules, 26(23): 7153, 2021 ”, which discloses quinolones structures, biological activity, and the clinical importance of this evolving family.

[0012] Reference may be made to the patent JP5421783B2, which discloses isoquinoline and isoquinolinone derivatives, their preparation and treatment and I or prevention of diseases associated with inhibition of Rho kinase-mediated phosphorylation of Rho kinase and / or myosin light chain phosphatase.

[0013] However, the current strategies for the synthesis of isoquinolone and quinolone skeletons involves intermolecular or intramolecular annular reactions among amides and alkynes with metal catalysts such as Co, Rh, Ru, Ni, Pd etc. It is well understood that the use of metal catalysts can pose environmental and safety threats while synthesizing the isoquinolone and quinolonesynthesis, and it is required to work toward more sustainable and responsible synthetic processes which does not need the presence of metals.

[0014] Despite the development of numerous synthetic methods to obtain these important heterocyclic scaffolds, there exist some drawbacks like multistep synthesis, use of transition metals, requirement of directing group, use of oxidants, tedious preparation, and harsh reaction conditions. Moreover, synthesizing both scaffolds typically requires distinct starting materials and synthetic routes, which can make the process exorbitant.

[0015] Accordingly, there is a dire need to develop an efficient isoquinolone and quinolone-based compounds and a method of synthesis thereof via transition-metal-free approach and from common starting materials in a controlled manner, with better yield, reactivity and activity.

[0016] The present invention relates to the field of pharmacology and covers the important core moiety in its compounds i.e., quinolone and / or isoquinolone. It provides a transition metal / heavy metal free catalytic system for production of substituted isoquinolone compounds via aryne intermediate formation which provides the desired compounds with yield in the range of 70-80%. Also, the present process is a single step process as compared to the multistep methods known in the art resulting into a method which is cost-effective, less time consuming and economic. It is of great value that the yield obtained by said process is 65-85%. Also, there is 98% conversion of starting material, and hence efficient as compared to the methods disclosed in the prior arts.

[0017] OBJECTS OF THE INVENTION

[0018] Main object of the present invention is to provide a process for the preparation of (un)substituted isoquinolone compound, derivative, analogue and salt form of Formula I, without the need of transition-metal-based catalyst.

[0019] Another object of the present invention is to provide a process for the preparation of (un)substituted quinolone compound, derivative, analogue and salt form of Formula IV, without the need of transition-metal-based catalyst.

[0020] Yet another object of the present invention is to provide a functionalized isoquinolones and a transition metal free approach for the synthesis of isoquinolones from the reaction of dimethyl-2- ((phenylamino)methylene) malonate with aryne precursors.

[0021] Yet another object of the present invention is to provide the compound of Formula I or IV useful in the process of preparation of drugs, active agents, alkaloids, and so on, e.g. antagonist agent AS2717638.

[0022] ABBREVIATIONS USED

[0023] TMS-Trimethyl Silyl group

[0024] Me2SiH-Dimethylsilane

[0025] OTf- triflate group

[0026] HMDS- Hexamethyldisilazane

[0027] THF-Tetrahydrofurane

[0028] DMF- Dimethyl formaide

[0029] Et2O -Diethyl ether n-BuLi- n-Butyllithium

[0030] Tf2O- Triflic anhydride

[0031] NaHCOs- Sodium bicarbonate

[0032] Na2SC>4- Sodium sulphate

[0033] CsF- Cesium fluoride

[0034] CS2CO3- Cesium Carbonate

[0035] ACN- Acetonitrile

[0036] CsOAc- Cesium Acetate

[0037] Na2CO3-Sodium Carbonate

[0038] K2CO3- Potassium carbonate

[0039] EtsN- Triethylamine

[0040] PhCN- Benzonitrile DME- Dimethoxyethane

[0041] KF- Potassium fluoride

[0042] TBAF- Tetrabutyl ammonium fluoride.

[0043] SUMMARY OF THE INVENTION

[0044] Accordingly, the present invention provides a process for the preparation of compound of Formula I or IV,

[0045] Formula I Formula IV or pharmaceutically acceptable salt thereof wherein R1, R2, R3, R4, R5, R6and R7are independently selected from the group consisting of hydrogen, (un)substituted alkyl (C1 to C21 ), (un)substituted alkoxy (C1 to C21 ), (un)substituted aryl (C5-C1 1 ), (un)substituted heteroaryl, silyl, alkylsilyl, (un)substituted alkylether, (un)substituted arylether, (un)substituted heteroarylether, (un)substituted alkynyl (C2-C12), (un)substituted alkylene (C2-C12), (un)substituted allyl (C2-C12), (un)substituted cyclic ring (C3-C12), (un)substituted cycloalkyl (C3-C12), heteroalkylene, arylalkyl, heteroarylalkyl, halo, nitro, (un)substitutedalkyl-ether-(un)substitutedaryl, (un)substitutedalkyl-ether-

[0046] (un)substitutedheteroaryl, (un)substitutedalkyl-ether-(un)substitutedalkyl, (un)substitutedalkyl- thio-(un)substitutedaryl, (un)substitutedalkyl-thio-(un)substitutedheteroaryl, (un)substitutedalkyl- thio-(un)substitutedalkyl, alkylaryl, alkylheteroaryl, alkylalkenyl, alkylalkenylalkyl, arylalkenyl, arylalkenylaryl, heterocycloalkyl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, (un)substituted alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate or carbonate; and optionally R1 with R2, R2 with R3, R3 with R4, R4 with R5, R5 with R6, or R6 with R7 together forms a ring which is unsubstituted or substituted with a substituent; and the process comprising the steps of: a) reacting a compound of Formula II with a substituted malonate compound of Formula III in presence of fluoride source, a solvent and an additive at temperature in the range of 25-120 C for time period in the range of 15-60 minutes to obtain the compound of Formula I

[0047] Formula II Formula III wherein R1-R7are same as defined above; R3a is C1 -C1 Oalkyl; R8 is selected from hydrogen, -NH2, -TMS, and -Me2SiH; and R9 is selected from -COOH, -OTf, and halogen; or b) reacting a compound of Formula V with a substituted malonate compound of Formula VI in presence of fluoride source, a solvent and an additive at temperature in the range of 25-120 °C for time period in the range of 2-12 h to obtain the compound of Formula IV

[0048] Formula V Formula VI wherein R1-R7are same as defined above; wherein the process is done without the need of catalyst and oxidant.

[0049] In an embodiment of the present invention, the R1 is selected from the group consisting of C1 -C12alkyl, C5-C8aryl, phenyl, halo-C5-C7phenyl, C1 -C12alkyl-C5-C7phenyl, nitro-C5-C7phenyl, trifluoro-C1 - C4alkyl, cyano-C5-C7phenyl, -COO-(C1 -C12)alkyl-(C5-C7)phenyl, C1 -C12alkoxy, naphthalenyl, anthracenyl, phenantherenyl, pyridinyl, methylbenzo[d]isoxazol-3-yl, C5-C7phenyl-(C1 -C12)alkyl, C5- C12-heteroaryl, and C3-C10heterocycloalkyl; R2 is hydrogen; R3 is C1 -C1 Oalkyl; R4, R5, R6 and R7 are independently selected from hydrogen, halogen, C1 -C12alkyl, trifluoro-C1 -C4alkyl, trifluoro-C5-C9aryl, C1 -C12alkoxy, nitro-C5-C7aryl, C5-C10aryl, halo-C5-C10aryl, C1 -C12alkyl-(C5-C10)aryl, -COO-(C1 - C4)alkyl, naphthalenyl, anthracenyl, phenantherenyl, pyridinyl, C1 -C4alkyl-C5-C8aryl, and C3- C8cycloalkyl; and R4 with R5, R5 with R6, or R6 with R7 together forms a dioxolo C3-C9cycloalkyl ring;R4 with R5, R5 with R6, or R6 with R7 together forms a C3-C8aryl ring; orR4 with R5, R5 with R6, or R6 with R7 together forms a C3-C8hetereoaryl ring.

[0050] In another embodiment of the present invention, the compound of Formula I is selected from the group consisting of:

[0051] 1 ) methyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3a),

[0052] 2) methyl-2-(4-fluorophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3b),

[0053] 3) methyl-2-(4-chlorophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3c),

[0054] 4) methyl-2-(4-bromophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3d),

[0055] 5) methyl-2-(4-iodophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3e),

[0056] 6) methyl-2-(2,4-difluorophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3f), 7) methyl-1 -oxo-2-(p-tolyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3g),

[0057] 8) methyl-2-(2-(tert-butyl)phenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3h),

[0058] 9) methyl-2-(4-nitrophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3i),

[0059] 10) methyl-1 -oxo-2-(4-(trifluoromethyl)phenyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3j),

[0060] 11 ) methyl-2-(4-cyanophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3k),

[0061] 12) methyl-2-(4-(ethoxycarbonyl)phenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (31),

[0062] 13) methyl-2-(4-methoxyphenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3m),

[0063] 14) ethyl-2-(4-methoxyphenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3n),

[0064] 15) methyl-2-(naphthalen-1 -yl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3o),

[0065] 16) methyl-1 -oxo-2-(pyridin-2-yl)-1 ,2-dihydroisoquinoline-4-carboxylate (3p),

[0066] 17) methyl-2-(5-methylbenzo[d]isoxazol-3-yl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3q),

[0067] 18) methyl-2-benzyl-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3r),

[0068] 19) methyl-1 -oxo-2-(thiophen-2-ylmethyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3s),

[0069] 20) methyl-2-(1 ,4-epoxynaphthalen-1 (4H)-ylmethyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3t),

[0070] 21 ) methyl-1 -oxo-2-((tetrahydrofuran-2-yl)methyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3u),

[0071] 22) methyl-2-cyclopropyl-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3v),

[0072] 23) methyl-6-chloro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3w),

[0073] 24) methyl-7-chloro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3w’),

[0074] 25) methyl-6-fluoro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3x),

[0075] 26) methyl-7-fluoro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3x’),

[0076] 27) methyl-6,7-difluoro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3y),

[0077] 28) methyl-6-methyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3z),

[0078] 29) methyl-7-methyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3z’),

[0079] 30) methyl-6,7-dimethyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3aa),

[0080] 31 ) methyl-1 -oxo-2-phenyl-6-(trifluoromethyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3bb),

[0081] 32) methyl-1 -oxo-2-phenyl-7-(trifluoromethyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3bb’)

[0082] 33) methyl-6-methoxy-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3cc),

[0083] 34) methyl-7-methoxy-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3cc’),

[0084] 35) methyl-8-methoxy-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3dd),

[0085] 36) methyl-5-oxo-6-phenyl-5,6-dihydro-[1 ,3]dioxolo[4,5-g]isoquinoline-8-carboxylate (3ee),

[0086] 37) methyl-1 -oxo-2-phenyl-1 ,2-dihydrobenzo[h]isoquinoline-4-carboxylate (3ff),

[0087] 38) methyl-1 -oxo-2-phenyl-1 ,2-dihydrobenzo[g]isoquinoline-4-carboxylate (3gg),

[0088] 39) methyl-6,7-dimethoxy-2-(5-methylbenzo[d]isoxazol-3-yl)-1 -oxo-1 ,2-dihydroisoquinoline-4- carboxylate (3hh), and

[0089] 40) methyl-5,8-dimethyl-2-(4-nitrophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3ei).

[0090] In another embodiment of the present invention, the compound of Formula IV is selected from the group consisting of:

[0091] 1 ) methyl-4-oxo-1 -phenyl-1 ,4-dihydroquinoline-3-carboxylate (4a),

[0092] 2) methyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4i), 3) methyl-7-chloro-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4b),

[0093] 4) methyl-6-chloro-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4b’),

[0094] 5) methyl-6,7-difluoro-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4c),

[0095] 6) methyl-6,7-dimethyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4d),

[0096] 7) methyl-5,8-dimethyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4e),

[0097] 8) methyl-1 -(4-nitrophenyl)-4-oxo-7-(trifluoromethyl)-1 ,4-dihydroquinoline-3-carboxylate (4f),

[0098] 9) methyl-1 -(4-nitrophenyl)-4-oxo-6-(trifluoromethyl)-1 ,4-dihydroquinoline-3-carboxylate (4f ),

[0099] 10) methyl-6,7-dimethoxy-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4g),

[0100] 1 1 ) methyl-5-(4-nitrophenyl)-8-oxo-5,8-dihydro-[1 ,3]dioxolo[4,5-g]quinoline-7-carboxylate (4h),

[0101] 12) methyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydrobenzo[g]quinoline-3-carboxylate (4j),

[0102] 13) methyl-5,8-dimethyl-4-oxo-1 -phenyl-1 ,4-dihydroquinoline-3-carboxylate (4k),

[0103] 14) methyl-1 -(4-fluorophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (41),

[0104] 15) methyl-1 -(4-chlorophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4m),

[0105] 16) methyl-2-(4-chlorophenyl)-5,8-dimethyl-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3mi),

[0106] 17) dimethyl-2-(((4-chlorophenyl)(2,5-dimethylphenyl)amino)methylene)malonate (4ma),

[0107] 18) methyl-1 -(4-iodophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4n),

[0108] 19) methyl-1 -(2,4-difluorophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4o),

[0109] 20) methyl-5,8-dimethyl-4-oxo-1 -(p-tolyl)-l ,4-dihydroquinoline-3-carboxylate (4p),

[0110] 21 ) methyl-5,8-dimethyl-4-oxo-1 -(4-(trifluoromethyl)phenyl)-1 ,4-dihydroquinoline-3-carboxylate (4q),

[0111] 22) methyl-1 -(4-(ethoxycarbonyl)phenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4r),

[0112] 23) methyl-1 -(4-methoxyphenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4s),

[0113] 24) methyl-5,8-dimethyl-1 -(naphthalen-1 -yl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4t),

[0114] 25) methyl-1 -benzyl-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4v), and

[0115] 26) methyl-1 -cyclopropyl-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4w).

[0116] In yet another embodiment of the present invention, the fluoride source is selected fromthe group consisting of cesium fluoride (CsF), KF, n-Bu4NF (TBAF), Tetra-n- butylammoniumdifluorotriphenylsilicate (TBAT), Me4NF, BnMesNF, and tris(dimethylamino)sulfoniumdifluorotrime-thylsilicate (TAS-F) or any combination thereof.

[0117] In yet another embodiment of the present invention, the solvent is selected from the group consisting of acetonitrile (ACN), THF, Benzonitriles, 1 ,4-dioxane, 1 ,2-dimethoxyethane (DME), 1 ,2- diethoxyethane(DEE), triglyme, Dichloromethane (DCM), N,N-dimethylfor-mamide (DMF), N,N- dimethylacetamide (DMA), acetone, EtOAc, chlorobenzene, methyltert-butyl ether (MTBE), butyronitriles (n-PrCN,i-PrCN), and DMSO or combination thereof.

[0118] In yet another embodiment of the present invention, the additive is selected from the group consisting of cesium carbonate (Cs2CO3), K2CO3, Na2COs, Li2COs, KHCO3, NaHCOs, (NFUJHCOs, t-BuOK, K3PO4, LiOAc, NaOAc, KOAc, CsOAc, NaOH, CsOPiv, EtsN, N,N,N',N'-tetramethylethylenediamine(TMEDA), pyridine, 2,6-lutidine, 1 ,8-diazabicyclo[5.4.0]-undec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), diisopropylethylamine (DIPEA), tetra-n-butylammoniurniodide (TBAI), tetra-n- butylammoniurnbrornide (TBAB), and 18-Crown-6 (18-C-6) or combination thereof.

[0119] In yet another embodiment of the present invention, the process is done under inert conditions by passing inert gas selected from the group consisting of argon, helium and nitrogen.

[0120] In yet another embodiment of the present invention, the process for preparation of Formula I or IV compound, comprising the steps of: a) preparing a reaction mixture-l comprising a compound of Formula II or V, fluorinating agent and additive in 1stsolvent at temperature in the range of 25-35 'C; b) preparing a reaction mixture-ll comprising a compound of Formula III or VI in a 2ndsolvent at temperature in the range of 25-350; c) slowly mixing the reaction mixture-ll in the reaction mixture-l at a temperature in the range of 25-120C for time period in the range of 2 to 10 h to obtain the compound of Formula I or IV; and d) optionally purifying the compound of step c) to obtain pure compound of Formula IV.

[0121] In yet another embodiment of the present invention, the 1stsolvent and 2ndsolvent are same or different and selected from the group consisting of acetonitrile (ACN), THF, Benzonitriles, 1 ,4-dioxane, 1 ,2- dimethoxyethane (DME), 1 ,2-diethoxyethane(DEE), triglyme, Dichloromethane (DCM), N,N-dimethylfor- mamide (DMF), N,N-dimethylacetamide (DMA), acetone, EtOAc, chlorobenzene, methyltert-butyl ether (MTBE), butyronitriles (n-PrCN,i-PrCN), and DMSO or any combination thereof.

[0122] BRIEF DESCRIPTION OF THE INVENTION

[0123] Fig. 1 represents process step for synthesis of Formula I and IV. wherein la falls under compound of Formula I; la’ falls under compound of Formula IV;

[0124] Ila falls under compound of Formula II and V;

[0125] Illa falls under compound of Formula III; and

[0126] Illa’ falls under compound of Formula VI.

[0127] DETAILED DESCRIPTION OF THE INVENTION

[0128] “Alkyl” as used herein is collection of carbon atoms that are covalently linked together in normal, secondary, tertiary or cyclic arrangements, i.e., in linear, branched, cyclic arrangement or some combination thereof. An alkyl substituent to structure is chain of carbon atoms that is covalently attached to structure through sp3carbon of substituent.

[0129] Cycloalkylas used here is a monocyclic, bicyclic or tricyclic ring system composed of only carbon atoms. The term “cycloalkyl” encompasses a monocyclic or polycyclic aliphatic, non-aromatic radical, wherein each of the atoms forming the ring (i.e. skeletal atoms) is a carbon atom. The number of carbon atoms in an cycloalkyl substituent, moiety or group can vary and typically is 3 to about 50, e.g., about 1 -30 or about 1 -20, unless otherwise specified, e.g., C3-8 alkyl or C3-C8 alkyl means an cycloalkyl substituent, moiety or group containing 3, 4, 5, 6, 7 or 8 carbon atoms and C3-6 alkyl or C3-C6 means an cycloalkyl substituent, moiety or group containing 3, 4, 5 or 6 carbon atoms. Cycloalkyl substituents, moieties or groups will typically have 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 carbon atoms and may contain exo or endo-cyclic double bonds or endo-cyclic triple bonds or a combination of both wherein the endo-cyclic double or triple bonds, or the combination of both, do not form a cyclic conjugated system of 4n+2 electrons; wherein the bicyclic ring system may share one (i.e., spiro ring system) or two carbon atoms and the tricyclic ring system may share a total of 2, 3 or 4 carbon atoms, typically 2 or 3.

[0130] “Alkylamine” as used herein means an — N(alkyl)xHygroup, moiety or substituent where x and y are independently selected from the group x=1 , y=1 and x=2, y=O. Alkylamine includes those — N(alkyl)xHygroups wherein x=2 and y=0 and the alkyl groups taken together with the nitrogen atom to which they are attached form a cyclic ring system.

[0131] “Aryl” as used here means aromatic ring system or fused ring system with no ring heteroatoms comprising 1 , 2, 3 or 4 to 6 rings, typically 1 to 3 rings, wherein rings are composed of only carbon atoms; and refers to a cyclically conjugated system of 4n+2 electrons (Huckel rule), typically 6, 10 or 14 electrons some of which may additionally participate in exocyclic conjugation (cross-conjugated (e.g., quinone). Aryl substituents, moieties or groups are typically formed by five, six, seven, eight, nine, or more than nine, carbon atoms. Aryl substituents, moieties or groups are optionally substituted. Exemplary aryls include Ce-C aryls such as phenyl and naphthalenyl and phenanthryl.

[0132] “Arylalkyl” as used herein means a substituent, moiety or group where an aryl moiety is bonded to an alkyl moiety, i.e., -alkyl-aryl, where alkyl and aryl groups are as described above, e.g., — CH2 — CeHs or — CH2CH(CH3) — CeHs. When arylalkyl is used as a Markush group (i.e., a substituent) the alkyl moiety of the arylalkyl is attached to a Markush Formula with which it is associated through a sp3carbon of the alkyl moiety.“Alkylaryl” as used herein means substituent, moiety or group where alkyl moiety is bonded to aryl moiety i.e. -aryl-alkyl, where aryl and alkyl groups are as described above, e.g. -CeFU-CHsor- C6H4-CH2CH(CH3).

[0133] “Further substituted with a substitution” may cover “substituted alkyl”, “substituted cycloalkyl”, “substituted alkenyl”, “substituted alkynyl”, substituted alkylaryl”, “substituted arylalkyl”, “substituted heterocycle”, “substituted aryl” and the like as used herein mean alkyl, alkenyl, alkynyl, alkylaryl, arylalkyl heterocycle, aryl or other group or moiety as defined or disclosed herein that has substituent(s) that replaces hydrogen atom(s) or substituent(s) that interrupts carbon atom chain. Alkenyl and alkynyl groups that comprise substituent(s) are optionally substituted at carbon that is one or more methylene moieties removed from double bond. Specific examples can be alkyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, cyano, halo, nitro, haloalkyl, fluoroalkyl, fluoroalkoxy, and amino, including mono- and di- substituted amino groups, and the protected derivatives thereof.

[0134] “Heterocycle”, “heteroaryl”, or “heterocyclic” as used herein means a cycloalkyl or aromatic ring system wherein one or more, typically 1 , 2 or 3, but not all of the carbon atoms comprising the ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically N, O or S wherein two or more heteroatoms may be adjacent to each other or separated by one or more carbon atoms, typically 1 -17 carbon atoms, 1 -7 atoms or 1 -3 atoms. Heterocycles include heteroaromatic rings (also known as heteroaryls) and heterocycloalkyl rings (also known as heteroalicyclic groups) containing one to four heteroatoms in the ring(s), where each heteroatom in the ring(s) is selected from O, S and N, wherein each heterocyclic group has from 4 to 10 atoms in its ring system, and with the proviso that the any ring does not contain two adjacent O or S atoms. Non-aromatic heterocyclic, substituents, moieties or groups (also known as heterocycloalkyls) have at least 3 atoms in their ring system and aromatic heterocyclic groups have at least 5 atoms in their ring system and include benzo-fused ring systems. Heterocyclics with 3, 4, 5, 6 and 10 atoms include azir idinylazetidinyl , thiazolyl, pyridyl and quinolinyl, respectively. Nonaromatic heterocyclic substituents, moieties / groups are pyrrolidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothienyl, oxazolidinonyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, thioxanyl, piperazinyl, aziridinyl, azetidinyl, oxetanyl, thietanyl, homopiperidinyl,3azabicyclo[4.1 ,0)heptanyl, 3H-indolyl and quinolizinyl.

[0135] “Heteroaryl” as used herein means an aryl ring system wherein one or more, typically 1 , 2 or 3, but not all of the carbon atoms comprising the aryl ring system are replaced by a heteroatom which is an atom other than carbon, including, N, O, S, Se, B, Si, P, typically, oxygen ( — O — ), nitrogen ( — NX — ) or sulfur ( — S — ) where X is — H, protecting group or 0-6 optionally substituted alkyl, wherein heteroatom participates in conjugated system either through pi-bonding with adjacent atom in ring system or through lone pair of electrons on heteroatom and may be optionally substituted on one or more carbons or heteroatoms, or combination of both, in manner which retains cyclically conjugated system. Examples of heteroaryls include by way of example and not limitation pyridyl, thiazolyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, purinyl, imidazolyl, benzofuranyl, indolyl, isoindoyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyridazinyl, pyrazinyl, benzothiopyran, benzotriazine, isoxazolyl, pyrazolopyrimidinyl, quinoxalinyl, thiadiazolyl, triazolyl and the like. Heterocycles that are not heteroaryls include, by way of example and not limitation, tetrahydrothiophenyl, tetrahydrofuranyl, indolenyl, piperidinyl, pyrrolidinyl, 2-pyrrolidonyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, piperazinyl, quinuclidinyl, morpholinyl, oxazolidinyl and the like.

[0136] “Heterocycloalkyl” or “heteroalicyclic” as used herein means cycloalkyl group or substituent wherein at least on carbon of cycloalkyl chain is replaces with heteroatom selected from nitrogen, oxygen and sulfur. The heterocycloalkyl may be fused with aryl or heteroaryl. Heterocycloalkyl includes, by way of example and not limitation, oxazolidinonyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothienyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, and indolinyl. Heteroalicyclics further includes all ring forms of carbohydrates, including but not limited to monosaccharides, disaccharides and oligosaccharides. Typically, heterocycloalkyl is C2- C10 heterocycloalkyl and includes C4-C10 heterocycloalkyl. Heterocycloalkyl may contain 0-2 N atoms, 0-2 O atoms or 0-1 S atoms.

[0137] “Heteroarylalkyl” as used herein means a substituent, moiety or group where a heteroaryl moiety is bonded to an alkyl moiety, i.e., -alkyl-heteroaryl, where alkyl and heteroaryl groups are as described above. When heteroarylalkyl is used as a Markush group (i.e., a substituent) the alkyl moiety of the heteroarylalkyl is attached to a Markush Formula with which it is associated through a sp3carbon of the alkyl moiety.“Alkylheteroaryl” as used herein means substituent, moiety or group where heteroaryl moiety is bonded to alkyl moiety, i.e., heteroaryl-alkyl, where heteroaryl and alkyl groups are as described above. When heteroarylalkyl is used as Markush group (substituent), heteroaryl moiety of heteroarylalkyl is attached to Markush Formula with which it is associated through sp2carbon or heteroatom of alkyl moiety.

[0138] “Halogen” or “halo” as used herein means fluorine, chlorine, bromine or iodine.

[0139] “Haloalkyl” as used herein means an alkyl substituent moiety or group in which one or more of its hydrogen atoms are replaced by one or more independently selected halide atoms. Haloalkyl includes C1-C4 haloalkyl. Example but non-limiting C1-C4 haloalkyls are — CH2CI, CH2Br, — CH2I, — CHBrCI, — CHCI — CH2CI and — CHCI — CH2I. “Haloalkylene” as used herein means an alkylene substituent, moiety or group in which one or more hydrogen atoms are replaced by one or more halide atoms. Haloalkylene includes Ci-Ce haloalkylenes or Ci-C4 haloalkylenes. “Fluoroalkyl” as used herein means an alkyl in which one or more hydrogen atoms are replaced by a fluorine atom. Fluoroalkyl includes Ci- Ce and C1-C4 fluoroalkyls. Example but non-limiting fluoroalkyls include — CH3F, — CH2F2 and — CFs and perfluroalkyls. “Fluoroalkylene” as used herein means an alkylene in which one or more hydrogen atoms are replaced by a fluorine atom. Fluoroalkylene includes Ci-Ce fluoroalkylenes or C1- C4 fluoroalkylenes.

[0140] The term “heteroalkyl” refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen, sulfur, phosphorus or combinations thereof. In one aspect, a heteroalkyl is a Ci-Ce heteroalkyl.

[0141] The present invention relates to a (un)substituted isoquinolone compounds, derivatives / analogues and salt forms thereof of Formula I wherein R1, R2, R3, R4, R5, R6and R7are independently selected from hydrogen, (un)substituted alkyl (C1 to C21 ), (un)substituted alkoxy (C1 to C21 ), (un)substituted aryl (C5-C1 1 ), (un)substituted heteroaryl, silyl, alkylsilyl, (un)substituted alkylether, (un)substituted arylether, (un)substituted heteroarylether, (un)substituted alkynyl (C2-C12), (un)substituted alkylene (C2-C12), (un)substituted allyl (C2-C12), (un)substituted cyclic ring (C3-C12), (un)substituted cycloalkyl (C3-C12), heteroalkylene, arylalkyl, heteroarylalkyl, halo, nitro, (un)substitutedalkyl-ether-(un)substitutedaryl, (un)substitutedalkyl-ether-(un)substitutedheteroaryl, (un)substitutedalkyl-ether-(un)substitutedalkyl, (un)substitutedalkyl-thio-(un)substitutedaryl, (un)substitutedalkyl-thio-(un)substitutedheteroaryl, (un)substitutedalkyl-thio-(un)substitutedalkyl, alkylaryl, alkylheteroaryl, alkylalkenyl, alkylalkenylalkyl, arylalkenyl, arylalkenylaryl, heterocycloalkyl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, (un)substituted alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate or carbonate; optionally R1 with R2, R2 with R3, R3 with R4, R4 with R5, R5 with R6, or R6 with R7 together forms a ring which may be further unsubstituted or substituted with a substituent.

[0142] In another embodiment, the R1, R2, R3, R4, R5, R6and R7are independently selected from hydrogen, (un)substituted alkyl, (un)substituted alkenyl, (un)substituted alkynyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted halo, (un)substituted cycloalkyl, (un)substituted heterocyclic alkyl, (un)substituted alkyl sulfonyl, etc.

[0143] In another embodiment, said ring is saturated or unsaturated ring.

[0144] In another embodiment, the ring is selected from but not limited to C3-C1 1 cycloalkyl, C3-C1 1 aryl, C3- C1 1 heteroaryl, etc.

[0145] In another embodiment, the ring is selected from but not limited to dioxolo ring, phenyl ring, benzyl ring, substituted phenyl ring, etc.

[0146] In an embodiment, the present invention discloses the compound of Formula I, wherein said compounds are Methyl-5-oxo-6-phenyl-5,6-dihydro-[1 ,3] dioxolo[4,5-g]isoquinoline-8-carboxylate; Methyl-6-chloro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate; Methyl-2-cyclopropyl-1 -oxo- 1 ,2-dihydroisoquinoline-4-carboxylate and Methyl-1 -oxo-2-phenyl-1 ,2-dihydrobenzo[h]isoquinoline-4- carboxylate and other related compounds.

[0147] The present disclosure pertains to a process of preparation of said substituted isoquinolone compounds, derivatives / analogues and salt forms thereof of Formula I by reacting substituted compound of Formula II with substituted malonate compound of Formula III in presence of fluoride source component, solvent and additive at specific reaction conditions and time period via aryne intermediate formation gives compounds of Formula I

[0148] Formula II Formula III wherein R1-R7as defined above, and R8 can be hydrogen, NH2, TMS, Me2SiH, etc., and R9 can be COOH, OTf, halogens.

[0149] The process is performed under mild reaction conditions at room temperature and under Argon atmosphere.

[0150] In another embodiment, to a flame dried two-neck round-bottom flask containing CsF (4.0 equiv), and CS2CO3 (2.5 equiv) in ACN (1 mL) was added II (3 equiv) at room temperature, under Argon atmosphere, followed by the addition of III (40 mg, 1 .0 equiv) in ACN (1 mL) dropwise at the same temperature. The two-neck round-bottom flask was then placed in a preheated (70 °C) oil bath; wherein, the progress of the reaction was monitored by TLC.

[0151] After completion of the reaction, reaction mixture was diluted with dichloromethane, filtered it and then was evaporated on a rotary evaporator. The crude product obtained were purified by flash silica gel column chromatography using a gradient of ethyl acetate:petroleum ether to afford the corresponding products I.

[0152] The fluoride source component is selected from but not limited to cesium fluoride (CsF), KF, n-Bu4NF (TBAF), Tetra-n-butylammoniumdifluorotriphenylsilicate (TBAT), Me4NF, BnMesNF, and tris(dimethylamino)sulfoniumdifluorotrime-thylsilicate (TAS-F) and a combination thereof.

[0153] The solvent is selected from but not limited to acetonitrile (ACN), THF, Benzonitriles, 1 ,4-dioxane, 1 ,2- dimethoxyethane (DME), 1 ,2-diethoxyethane(DEE), triglyme, Dichloromethane (DCM), N,N- dimethylfor-mamide (DMF), N,N-dimethylacetamide (DMA), acetone, EtOAc, chlorobenzene, methyltert-butyl ether (MTBE), butyronitriles (n-PrCN,i-PrCN), and DMSO and a combination thereof.

[0154] The additive or base is selected from but not limited tocesium carbonate (Cs2CO3), K2CO3, Na2COs, U2CO3, KHCO3, NaHCO3, (NH4)HCO3, t-BuOK, K3PO4, LiOAc, NaOAc, KOAc, CsOAc, NaOH, CsOPiv, EtsN, N,N,N',N'-tetramethylethylenediamine(TMEDA), pyridine, 2,6-lutidine, 1 ,8-diazabicyclo[5.4.0]- undec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), and diisopropylethylamine (DIPEA), phase transfer catalysts, such as tetra-n-butylammoniumiodide (TBAI) and bromide (TBAB), 18-Crown- 6 (18-C-6).

[0155] The process is performed at the temperature ranging from 20°C to 120°C, preferably between 60°C- 80°C.

[0156] The process provides an enhanced yield of isoquinolone without any catalyst and oxidant. The process is cost effective and efficient.

[0157] The present invention discloses a process for the synthesis of methyl 5-oxo-6-phenyl-5,6-dihydro- [1 ,3] dioxolo[4,5-g]isoquinoline-8-carboxylate (lb); comprising steps of; i. To a flame dried two-neck round-bottom flask containing CsF (103 mg, 0.68 mmol, 4.0 equiv), and Cs2CO3 (140 mg, 0.43 mmol, 2.5 equiv) in ACN (1 mL), adding lib (174.9 mg, 0.51 mmol, 3 equiv) at room temperature, under Argon atmosphere; ii. Adding Illa (40 mg, 0.17 equiv) in ACN (1 mL) dropwise at the same temperature.

[0158] Hi. placing the two-neck round-bottom flask in a preheated (70 °C) oil bath; iv. monitoring the progress of the reaction by TLC; v. diluting the reaction mixture with 5 ml dichloromethane after completion of the reaction, followed by filtering and evaporating on a rotary evaporator; vi. purifying the crude product obtained by flash silica gel column chromatography using a gradient of ethyl acetate:petroleum ether (1 :9); and vii. obtaining the corresponding products lb in 70 % yield (38.5 mg).

[0159] The compound II is can be prepared easily by literature methods which are cost effective, the compound III also prepared by easily available dialkyl malonate and amines both are very cheap. The CsF and CS2CO3 and the solvent ACN also not expensive.

[0160] In a given process there is no use of any expensive metal catalyst and oxidant.

[0161] The present invention discloses a method for synthesizing the compound I, comprising the steps of: i) to a flame dried two-neck round-bottom flask containing CsF (4.0 equiv), and Cs2CO3 (2.5 equiv) in ACN (1 mL) adding II (3 equiv) at room temperature, under Argon atmosphere; ii) adding III (40 mg, 1 .0 equiv) in ACN (1 mL) dropwise at the room temperature; iii) placing the two-neck round-bottom flask in a preheated (70 C) oil bath; iv) monitoring the progress of the reaction by TLC; v) diluting the reaction mixture with dichloromethane after completion of reaction; vi) filtering and evaporating the reaction mixture on a rotary evaporator; vii) purifying the crude product by flash silica gel column chromatography using a gradient of ethyl acetate:petroleum ether; and viii) obtaining the corresponding products I.

[0162] The present invention discloses the compounds of Formula I, wherein said compounds are Methyl-5- oxo-6-phenyl-5,6-dihydro-[1 ,3] dioxolo[4,5-g]isoquinoline-8-carboxylate; Methyl-6-chloro-1 -oxo-2- phenyl-1 ,2-dihydroisoquinoline-4-carboxylate; Methyl-2-cyclopropyl-1 -oxo-1 ,2-dihydroisoquinoline-4- carboxylate and Methyl-1 -oxo-2-phenyl-1 ,2-dihydrobenzo[h]isoquinoline-4-carboxylate and other related compounds.

[0163] The present method is the powerful one-step strategy for the development of highly functionalized isoquinolone skeleton. Further, mild reaction condition is used with moderate temperature condition. The process does not require any directing group attached to the substrates or any oxidant to complete the reaction. The present invention can be proven significant in the field of pharmacology as isoquinolone containing scaffolds are present in most of biologically active molecules and the method can also be extended to natural product and API synthesis e.g. floxacin, and their analogues / derivatives.

[0164] The present invention provides (un)substituted quinolone compounds, and derivatives, analogues, and / or salt forms thereof of Formula IV, represented by:

[0165] Formula IV wherein R1, R2, R3, R4, R5, R6, and R7are independently selected from hydrogen, (un)substituted alkyl (C1 to C21 ), (un)substituted alkoxy (C1 to C21 ), (un)substituted aryl (C5-C1 1 ), (un)substituted heteroaryl, silyl, alkylsilyl, (un)substituted alkylether, (un)substituted arylether, (un)substituted heteroarylether, (un)substituted alkynyl (C2-C12), (un)substituted alkylene (C2-C12), (un)substituted allyl (C2-C12), (un)substituted cyclic ring (C3-C12), (un)substituted cycloalkyl (C3-C12), heteroalkylene, arylalkyl, heteroarylalkyl, halo, nitro, (un)substitutedalkyl-ether-(un)substitutedaryl, (un)substitutedalkyl-ether-(un)substitutedheteroaryl, (un)substitutedalkyl-ether-(un)substitutedalkyl, (un)substitutedalkyl-thio-(un)substitutedaryl, (un)substitutedalkyl-thio-(un)substitutedheteroaryl, (un)substitutedalkyl-thio-(un)substitutedalkyl, alkylaryl, alkylheteroaryl, alkylalkenyl, alkylalkenylalkyl, arylalkenyl, arylalkenylaryl, heterocycloalkyl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, (un)substituted alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate or carbonate; and optionally R1 with R2, R3 with R4, R4 with R5, R5 with R6, orR6 with R7together forms a ring which may be further unsubstituted or substituted with a substituent.

[0166] In another embodiment, the R1, R2, R3, R4, R5, R6, and R7are independently selected from hydrogen, (un)substituted alkyl, (un)substituted alkenyl, (un)substituted alkynyl, (un)substituted aryl, (un)substituted heteroaryl, (un)substituted halo, (un)substituted cycloalkyl, (un)substituted heterocyclic alkyl, (un)substituted alkyl sulfonyl, etc.

[0167] In another embodiment, said ring is saturated or unsaturated ring.

[0168] In another embodiment, the ring is selected from but not limited to C3-C1 1 cycloalkyl, C3-C1 1 aryl, C3- C1 1 heteroaryl, etc.

[0169] In another embodiment, the ring is selected from but not limited to dioxolo ring, phenyl ring, benzyl ring, substituted phenyl ring, etc.

[0170] The present invention provides a process of preparation of said compounds of Formula IV, comprising steps of: a) preparing a reaction mixture-l comprising a compound of Formula V, fluorinating agent and base or additive in 1stsolvent at temperature in the range of 25-35 °C; b) preparing a reaction mixture-ll comprising a compound of Formula VI in a 2ndsolvent at temperature in the range of 25-35 °C; c) slowly mixing the reaction mixture-ll in the reaction mixture-l at a temperature in the range of 50 to 90 °C for time period in the range of 2 to 6 h to obtain the compound of Formula II; and d) optionally purifying compound of step c) to obtain pure compound of Formula IV.

[0171] The fluorinating agent is selected from cesium fluoride (CsF), KF, n-Bu4NF (TBAF), Tetra-n- butylammoniumdifluorotriphenylsilicate (TBAT), Me4NF, BnMesNF, and tris(dimethylamino)sulfoniumdifluorotrime-thylsilicate (TAS-F) and a combination thereof.

[0172] The additive or base is selected from cesium carbonate (Cs2CO3), K2CO3, Na2COs, IJ2CO3, KHCO3, NaHCO3, (NH4)HCO3, t-BuOK, K3PO4, LiOAc, NaOAc, KOAc, CsOAc, NaOH, CsOPiv, Et3N, N,N,N',N'- tetramethylethylenediamine(TMEDA), pyridine, 2,6-lutidine, 1 ,8-diazabicyclo[5.4.0]-undec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), and diisopropylethylamine (DIPEA), phase transfer catalysts, such as tetra-n-butylammoniumiodide (TBAI) and bromide (TBAB), 18-Crown-6 (18-C-6). and so on.

[0173] In another embodiment, the 1stsolvent is selected from ACN, PhCN, DME and so on.

[0174] In another embodiment, the 2ndsolvent is selected from ACN, PhCN, DME and so on.

[0175] In another embodiment, the purification is done by first diluting with dichloromethane, filtering it and then evaporated on a rotary evaporator; followed by subjecting it to flash silica gel column chromatography using a gradient of ethyl acetate:petroleum ether to afford the pure compounds of Formula IV.

[0176] The yield of compound of Formula I or IV is in the range of 50-75%.

[0177] The selectivity of compound of Formula I is in the range of 60-85%.

[0178] The selectivity of compound of Formula IV is in the range of 60-85%.

[0179] EXAMPLES

[0180] Following examples are given by way of illustration and therefore should not be construed to limit the scope of the present invention.

[0181] Example 1 : General Procedure for the synthesis of compound II

[0182] A mixture of o-bromohydroxyarene (1 .0 equiv) and HMDS (1 .2-1 .6 equiv) was stirred at 80 °C for 45 min in a flask protected with a CaCl2 tube. Excess NH3 and unreacted HMDS were then removed under vacuum, and after1H NMR confirmation of the quantitative formation of the corresponding silyl ether, the crude product was dissolved in THF (0.15 M), the solution was cooled to -100 °C (external temperature, liquid N2 / Et2O bath) and BuLi (1 .1 equiv) was added dropwise. The mixture was stirred for 20 min while the temperature reached -80 °C. Then the mixture was again cooled to -100 °C, Tf2O (1 .2 equiv) was added dropwise, and stirring was continued for 20 min while the temperature reached to - 80 °C. Cold sat. aq NaHCOs was added, the two phases were separated and the aqueous layer was extracted with Et20. The combined organic layers were dried (Na2SC>4), filtered, and concentrated under reduced pressure. Purification of the residue by column chromatography (SiC ) afforded the corresponding tritiate, (compound II was synthesized as per the procedure reported inPena, D.; Cobas, A.; Perez, D.; Guitian, E. Synthesis 2002, 10,1454.) This was observed that the characterization data for compound II exactly matched with the reported data as per reference. (Pena, D.; Cobas, A.; Perez, D.; Guitian, E. Synthesis 2002, 10,1454.)

[0183] Example 2: General procedure for the synthesis of compound of Formula III or VI

[0184] To a solution of aniline or amine (1 equiv) in ethanol or methanol (5% w / v) dimethyl ethoxy-methylene malonate (1 equiv) was added and stirred at room temperature (~28 °C). After the reaction had been completed, ethanol or methanol was evaporated from the reaction mixture under reduced pressure. Purification of the residue by column chromatography (SiOa) afforded the corresponding product III in 77-99% yield.

[0185] The compound III was synthesized as per the procedure reported in J. Am. Chem. Soc., 61 (1939), pp. 2890-2895 and the characterization data for compound II exactly matched with the reported data as per reference (J. Am. Chem. Soc., 61 (1939), pp. 2890-2895).

[0186] A) Dimethyl 2-((phenylamino)methylene) malonate

[0187] White solid (90%) R 0 30 ( et ether / eth l acetate 8:2)1H NMR (400 MHz CDCI ):6

[0188] Scheme 3

[0189] To a flame dried two-neck round-bottom flask containing CsF (103 mg, 0.68 mmol, 4.0 equiv), and CS2CO3 (140 mg, 0.43 mmol, 2.5 equiv) in ACN (1 mL) was added lib (174.9 mg, 0.51 mmol, 3 equiv) at room temperature, under Argon atmosphere, followed by the addition of Illa (40 mg, 0.17 equiv) in ACN (1 mL) dropwise at the same temperature. The two-neck round-bottom flask was then placed in a preheated (70 °C) oil bath. The progress of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with 5 ml dichloromethane, filtered it and then was evaporated on a rotary evaporator. The crude product obtained were purified by flash silica gel column chromatography using a gradient of ethyl acetate petroleum ether (1 :9) to afford the corresponding products 3ee in 70 % yield (38.5 mg). a) Methyl 1-oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3a).

[0190] White solid (36.3 mg, 77%); Rf = 0.31 (pet ether / ethyl acetate = 9:1 );nH NMR (400 MHz, CDCI3):6 8.88 (d, J = 8.4 Hz, 1 H), 8.51 (dd, J = 8.1 , 1.1 Hz, 1 H), 8.24 (s, 1 H), 7.79 (ddd, J = 8.4, 7.1 , 1.4 Hz, 1 H), 7.61 - 7.53 (m, 3 H), 7.53 - 7.43 (m, 3 H), 3.93 (s, 3 H). b) Methyl-5-oxo-6-phenyl-5,6-dihydro-[1 ,3]dioxolo[4,5-g]isoquinoline- 8-carboxylate (3ee). White solid (38.5 mg, 70 %); Rf = 0.2.9 (pet ether / ethyl acetate = 9:1 );1H NMR (400 MHz, CDCI3):68.34 (s, 1 H), 8.18 (s, 1 H), 7.83 (s, 1 H) 7.58-7.50 (m, 2H), 7.49-7.40 (m, 3H), 6.13 (s, 2H), 3.88 (s, 3H);13C NMR (100 MHz, CDCh):5 165.7, 161.1 1 , 152.89, 148.05, 140.64, 138.99, 131.77, 129.44, 128.70, 126.81 , 121.54, 106.69, 106.27, 104.07, 102.05, 51 .85.

[0191] :) Methyl 2-cyclopropyl-1-oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3v).

[0192] White solid (37 mg, 76 %); Rf = 0.38 (pet ether / ethyl acetate = 9:1 );1H NMR (400MHz, CDCI3):68.77 (d, J = 8.3 Hz, 1 H), 8.50 - 8.38 (m, 1 H), 8.18 (s, 1 H), 7.78 - 7.67 (m, 1 H), 7.58- 7.46 (m, 1 H), 3.92 (s, 3 H), 3.46 - 3.35 (m, 1 H), 1 .20 (q, J = 6.8 Hz, 2 H), 0.93 - 0.98 (m, 2 H).13C NMR (100 MHz, CDCI3): 6 165.7, 163.5, 139.6, 133.9, 133.1 , 129.1 , 127.9, 127.2, 125.4, 125.2, 106.4, 51.8, 32.5, 6.9.

[0193] Compound of Formula I of the compounds having a Formula I are listed below:

[0194] Example 4: Reaction scheme and process steps / experiment procedure.

[0195] The method disclosed in the present invention is used for the total synthesis of antimalarial agent SJ000101247. The planned reaction scheme for this molecule as given below. There is another way by taking a substrate having a thiophene substituted A which does not require the coupling.

[0196] Synthesis of antimalarial agent SJ000101247

[0197] The compound of Formula I can also be used in the synthesis of following drugs.

[0198] Ruprechstyril Gusanlung D Dorianine

[0199] Example 5: General procedure for the synthesis of compound of Formula IV (I').

[0200] To a flame dried two-neck round-bottom flask containing CsF (4.0 equiv), and CS2CO3 (2.5 equiv) in ACN or PhCN or DME (1 mL) was added II (3 equiv) at room temperature, under Argon atmosphere, followed by the addition of III (40 mg, 1 .0 equiv) in ACN or PhCN or DME (1 mL) dropwise at the same temperature. The two-neck round-bottom flask was then placed in a preheated (70 to 140°C) oil bath. The progress of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with dichloromethane, filtered it and then was evaporated on a rotary evaporator. The crude product obtained were purified by flash silica gel column chromatography using a gradient of ethyl acetate:petroleum ether to afford the corresponding products I'.

[0201] Some floxacin moiety containing drugs. a) Typical procedure for the synthesis of methyl 1-(4-nitrophenyl)-4-oxo-1,4-dihydroquinoline- 3-carboxylate (4a).

[0202] To a flame dried two-neck round-bottom flask containing CsF (4.0 equiv), and CS2CO3 (2.5 equiv) in ACN or PhCN or DME (1 mL) was added lib (3 equiv) at room temperature, under Argon atmosphere, followed by the addition of Illa' (40 mg, 1 .0 equiv) in ACN or PhCN or DME (1 mL) dropwise at the same temperature. The two-neck round-bottom flask was then placed in a preheated (100°C) oil bath. The progress of the reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with dichloromethane, filtered it and then was evaporated on a rotary evaporator. The crude product obtained were purified by flash silica gel column chromatography using a gradient of ethyl acetate:petroleum ether to afford the corresponding products 4a approximately in 70%.

[0203] Compounds of Formula IV

[0204] Many of the compounds having a Formula IV are listed below:

[0205] Example 6: Synthesis of AS2717638 along with its characterization data. ADVANTAGES OF THE INVENTION The given protocol is transition metal free and ligand free approach for the synthesis of isoquinolones. Mild reaction condition is used with moderate temperature condition. No need of any directing group attached to the substrates. No need of any oxidant. The present method provides an expected isoquinolone in good to excellent yield. The isoquinolone containing scaffolds are present in most of biologically active molecules. The method can be extended to natural product and API synthesis. The method also useful for the synthesis of quinolones i.e., floxacin class of APIs and their analogues.

Claims

WE CLAIM1 . A process for the preparation of compound of Formula I or IV,Formula I Formula IV or pharmaceutically acceptable salt thereof wherein R1, R2, R3, R4, R5, R6and R7are independently selected from the group consisting of hydrogen, (un)substituted alkyl (C1 to C21), (un)substituted alkoxy (C1 to C21 ), (un)substituted aryl (C5-C1 1 ), (un)substituted heteroaryl, silyl, alkylsilyl, (un)substituted alkylether, (un)substituted arylether, (un)substituted heteroarylether, (un)substituted alkynyl (C2-C12), (un)substituted alkylene (C2-C12), (un)substituted allyl (C2-C12), (un)substituted cyclic ring (C3-C12), (un)substituted cycloalkyl (C3-C12), heteroalkylene, arylalkyl, heteroarylalkyl, halo, nitro, (un)substitutedalkyl-ether- (un)substitutedaryl, (un)substitutedalkyl-ether-(un)substitutedheteroaryl,(un)substitutedalkyl-ether-(un)substitutedalkyl, (un)substitutedalkyl-thio-(un)substitutedaryl, (un)substitutedalkyl-thio-(un)substitutedheteroaryl,(un)substitutedalkyl-thio-(un)substitutedalkyl, alkylaryl, alkylheteroaryl, alkylalkenyl, alkylalkenylalkyl, arylalkenyl, arylalkenylaryl, heterocycloalkyl, haloalkyl, heteroalkyl, alkylamino, alkoxycarbonyl, alkylcarbonyl, alkylcarbonylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, aminosulfonylamino, aminocarbonylamino, alkylaminosulfonylamino, dialkylaminosulfonylamino, alkylaminocarbonylamino, alkylcarbamoyl, alkylthio, alkylsulfinyl, (un)substituted alkylsulfonyl, carbamyl, cyano-alkyl, alkoxyalkyl, dialkylamino, dialkylcarbamyl, haloalkoxy, haloalkyl, ester, ether, acetal, thioacetal, ketal, thioketal, carbamate or carbonate; and optionally R1 with R2, R2 with R3, R3 with R4, R4 with R5, R5 with R6, or R6 with R7 together forms a ring which is unsubstituted or substituted with a substituent; and the process comprising the steps of: a) reacting a compound of Formula II with a substituted malonate compound of Formula III in presence of fluoride source, a solvent and an additive at temperaturein the range of 25-120 C for time period in the range of 15-60 minutes to obtain the compound of Formula IFormula II Formula III wherein R1-R7are same as defined above; R3a is C1 -C1 Oalkyl; R8 is selected from hydrogen, -NH2, -TMS, and -MesSiH; and R9 is selected from -COOH, -OTf, and halogen; or b) reacting a compound of Formula V with a substituted malonate compound of Formula VI in presence of fluoride source, a solvent and an additive at temperature in the range of 25-120 °C for time period in the range of 2-12 h to obtain the compound of Formula IVFormula V Formula VI wherein R1-R7are same as defined above; wherein the process is done without the need of catalyst and oxidant.

2. The process as claimed in claim 1 , wherein the R1 is selected from the group consisting of C1 -C12alkyl, C5-C8aryl, phenyl, halo-C5-C7phenyl, C1 -C12alkyl-C5-C7phenyl, nitro-C5- C7phenyl, trifluoro-C1 -C4alkyl, cyano-C5-C7phenyl, -COO-(C1 -C12)alkyl-(C5-C7)phenyl, C1 -C12alkoxy, naphthalenyl, anthracenyl, phenantherenyl, pyridinyl, methylbenzo[d]isoxazol-3-yl, C5-C7phenyl-(C1 -C12)alkyl, C5-C12-heteroaryl, and C3- Cl Oheterocycloalkyl; R2 is hydrogen; R3 is C1 -C1 Oalkyl; R4, R5, R6 and R7 are independently selected from hydrogen, halogen, C1 -C12alkyl, trifluoro-C1 -C4alkyl, trifluoro-C5-C9aryl, C1 -C12alkoxy, nitro-C5-C7aryl, C5-C10aryl, halo-C5-C10aryl, C1 - C12alkyl-(C5-C10)aryl, -COO-(C1 -C4)alkyl, naphthalenyl, anthracenyl, phenantherenyl, pyridinyl, C1 -C4alkyl-C5-C8aryl, and C3-C8cycloalkyl; and R4 with R5, R5 with R6, or R6 with R7 together forms a dioxolo C3-C9cycloalkyl ring ;R4 with R5, R5 with R6, or R6 with R7 together forms a C3-C8aryl ring; orR4 with R5, R5 with R6, or R6 with R7 togetherforms a C3-C8hetereoaryl ring.

3. The process as claimed in claim 1 , wherein the compound of Formula I is selected from the group consisting of:I ) methyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3a),2) methyl-2-(4-fluorophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3b),3) methyl-2-(4-chlorophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3c),4) methyl-2-(4-bromophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3d),5) methyl-2-(4-iodophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3e),6) methyl-2-(2,4-difluorophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3f),7) methyl-1 -oxo-2-(p-tolyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3g),8) methyl-2-(2-(tert-butyl)phenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3h),9) methyl-2-(4-nitrophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3i),10) methyl-1 -oxo-2-(4-(trifluoromethyl)phenyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3j),I I ) methyl-2-(4-cyanophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3k),12) methyl-2-(4-(ethoxycarbonyl)phenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (31),13) methyl-2-(4-methoxyphenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3m),14) ethyl-2-(4-methoxyphenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3n),15) methyl-2-(naphthalen-1 -yl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3o),16) methyl-1 -oxo-2-(pyridin-2-yl)-1 ,2-dihydroisoquinoline-4-carboxylate (3p),17) methyl-2-(5-methylbenzo[d]isoxazol-3-yl)-1 -oxo-1 ,2-dihydroisoquinoline-4- carboxylate (3q),18) methyl-2-benzyl-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3r),19) methyl-1 -oxo-2-(thiophen-2-ylmethyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3s),20) methyl-2-(1 ,4-epoxynaphthalen-1 (4H)-ylmethyl)-1 -oxo-1 ,2-dihydroisoquinoline-4- carboxylate (3t),21 ) methyl-1 -oxo-2-((tetrahydrofuran-2-yl)methyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3u),22) methyl-2-cyclopropyl-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3v),23) methyl-6-chloro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3w),24) methyl-7-chloro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3w’),25) methyl-6-fluoro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3x),26) methyl-7-fluoro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3x’),27) methyl-6,7-difluoro-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3y),28) methyl-6-methyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3z),29) methyl-7-methyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3z’),30) methyl-6,7-dimethyl-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3aa),31 ) methyl-1 -oxo-2-phenyl-6-(trifluoromethyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3bb),32) methyl-1 -oxo-2-phenyl-7-(trifluoromethyl)-1 ,2-dihydroisoquinoline-4-carboxylate (3bb’)33) methyl-6-methoxy-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3cc),34) methyl-7-methoxy-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3cc’),35) methyl-8-methoxy-1 -oxo-2-phenyl-1 ,2-dihydroisoquinoline-4-carboxylate (3dd),36) methyl-5-oxo-6-phenyl-5,6-dihydro-[1 ,3]dioxolo[4,5-g]isoquinoline-8-carboxylate (3ee),37) methyl-1 -oxo-2-phenyl-1 ,2-dihydrobenzo[h]isoquinoline-4-carboxylate (3ff),38) methyl-1 -oxo-2-phenyl-1 ,2-dihydrobenzo[g]isoquinoline-4-carboxylate (3gg),39) methyl-6,7-dimethoxy-2-(5-methylbenzo[d]isoxazol-3-yl)-1 -oxo-1 ,2- dihydroisoquinoline-4-carboxylate (3hh), and40) methyl-5,8-dimethyl-2-(4-nitrophenyl)-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3ei).

4. The process as claimed in claim 1 , wherein the compound of Formula IV is selected from the group consisting of:I ) methyl-4-oxo-1 -phenyl-1 ,4-dihydroquinoline-3-carboxylate (4a),2) methyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4i),3) methyl-7-chloro-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4b),4) methyl-6-chloro-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4b’),5) methyl-6,7-difluoro-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4c),6) methyl-6,7-dimethyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4d),7) methyl-5,8-dimethyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4e),8) methyl-1 -(4-nitrophenyl)-4-oxo-7-(trifluoromethyl)-1 ,4-dihydroquinoline-3-carboxylate (4f),9) methyl-1 -(4-nitrophenyl)-4-oxo-6-(trifluoromethyl)-1 ,4-dihydroquinoline-3-carboxylate (4f’)>10) methyl-6,7-dimethoxy-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4g),I I ) methyl-5-(4-nitrophenyl)-8-oxo-5,8-dihydro-[1 ,3]dioxolo[4,5-g]quinoline-7-carboxylate (4h),12) methyl-1 -(4-nitrophenyl)-4-oxo-1 ,4-dihydrobenzo[g]quinoline-3-carboxylate (4j),13) methyl-5,8-dimethyl-4-oxo-1-phenyl-1 ,4-dihydroquinoline-3-carboxylate (4k),14) methyl-1 -(4-fluorophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4I),15) methyl-1 -(4-chlorophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4m),16) methyl-2-(4-chlorophenyl)-5,8-dimethyl-1 -oxo-1 ,2-dihydroisoquinoline-4-carboxylate (3mi),17) dimethyl-2-(((4-chlorophenyl)(2,5-dimethylphenyl)amino)methylene)malonate (4ma),18) methyl-1 -(4-iodophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4n),19) methyl-1 -(2,4-difluorophenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4o),20) methyl-5,8-dimethyl-4-oxo-1 -(p-tolyl)- 1 ,4-dihydroquinoline-3-carboxylate (4p),21 ) methyl-5,8-dimethyl-4-oxo-1 -(4-(trif luoromethyl)phenyl)- 1 ,4-dihydroquinoline-3- carboxylate (4q),22) methyl-1 -(4-(ethoxycarbonyl)phenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3- carboxylate (4r),23) methyl-1 -(4-methoxyphenyl)-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4s),24) methyl-5,8-dimethyl-1 -(naphthalen-1 -yl)-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4t),25) methyl-1 -benzyl-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4v), and26) methyl-1 -cyclopropyl-5,8-dimethyl-4-oxo-1 ,4-dihydroquinoline-3-carboxylate (4w).

5. The process as claimed in claim 1 , wherein the fluoride source is selected from the group consisting of cesium fluoride (CsF), KF, n-Bu4NF (TBAF), Tetra-n- butylammoniumdifluorotriphenylsilicate (TBAT), Me4NF, BnMesNF, and tris(dimethylamino)sulfoniumdifluorotrime-thylsilicate (TAS-F) or any combination thereof.

6. The process as claimed in claim 1 , wherein the solvent is selected from the group consisting of acetonitrile (ACN), THF, Benzonitriles, 1 ,4-dioxane, 1 ,2-dimethoxyethane (DME), 1 ,2-diethoxyethane(DEE), triglyme, Dichloromethane (DCM), N,N-dimethylfor- mamide (DMF), N,N-dimethylacetamide (DMA), acetone, EtOAc, chlorobenzene, methyltert-butyl ether (MTBE), butyronitriles (n-PrCN,i-PrCN), and DMSO or combination thereof.

7. The process as claimed in claim 1 , wherein the additive is selected from the group consisting of cesium carbonate (Cs2CO3), K2CO3, NasCOs, U2CO3, KHCO3, NaHCOs, (NH4)HCO3, t-BuOK, K3PO4, LiOAc, NaOAc, KOAc, CsOAc, NaOH, CsOPiv, Et3N, N,N,N',N'-tetramethylethylenediamine(TMEDA), pyridine, 2,6-lutidine, 1 ,8-diazabicyclo[5.4.0]-undec-7-ene (DBU), 1 ,4-diazabicyclo[2.2.2]octane (DABCO), diisopropylethylamine (DIPEA), tetra-n-butylammoniumiodide (TBAI), tetra-n- butylammoniumbromide (TBAB), and 18-Crown-6 (18-C-6) or combination thereof.

8. The process as claimed in claim 1 , wherein the process is done under inert conditions by passing inert gas selected from the group consisting of argon, helium and nitrogen.

9. The process as claimed in claim 1 , wherein the process for preparation of Formula I or IV compound, comprising the steps of: a) preparing a reaction mixture-l comprising a compound of Formula II or V, fluorinating agent and additive in 1stsolvent at temperature in the range of 25-350; b) preparing a reaction mixture-ll comprising a compound of Formula III or VI in a 2ndsolvent at temperature in the range of 25-350; c) slowly mixing the reaction mixture-ll in the reaction mixture-l at a temperature in the range of 25-120C for time period in the range of 2 to 10 h to obtain the compound of Formula I or IV; and d) optionally purifying the compound of step c) to obtain pure compound of Formula IV.

10. The process as claimed in claim 9, wherein the 1stsolvent and 2ndsolvent are same or different and selected from the group consisting of acetonitrile (ACN), THF, Benzonitriles, 1 ,4-dioxane, 1 ,2-dimethoxyethane (DME), 1 ,2-diethoxyethane(DEE), triglyme, Dichloromethane (DCM), N,N-dimethylfor-mamide (DMF), N,N- dimethylacetamide (DMA), acetone, EtOAc, chlorobenzene, methyltert-butyl ether (MTBE), butyronitriles (n-PrCN,i-PrCN), and DMSO or any combination thereof.

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