CHAUDHARI SACHIN (IN)
GOWDA NAGARAJ (IN)
DAS SANJIB (IN)
IYER PRAVIN (IN)
WAGHMARE NAYAN (IN)
SHELKE SANDEEP (IN)
GAVHANE BALASAHEB (IN)
SAINI JAGMOHAN (IN)
KADAM SHEETAL (IN)
WO2022169998A1 | 2022-08-11 | |||
WO2021021761A1 | 2021-02-04 | |||
WO2020236654A1 | 2020-11-26 | |||
WO2021061853A1 | 2021-04-01 | |||
WO2021061870A1 | 2021-04-01 | |||
WO2021021761A1 | 2021-02-04 | |||
WO2020264398A1 | 2020-12-30 | |||
WO2020236654A1 | 2020-11-26 | |||
WO2020210508A1 | 2020-10-15 | |||
WO2019148005A1 | 2019-08-01 |
IN202221046493A | 2022-08-16 |
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WHAT IS CLAIMED IS: 1. A compound of formula (I) or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein, at each occurrence, R1 is selected independently from 3-15 membered heterocyclylC1- 8alkyl, 5-14 membered heteroarylC1-8alkyl and –[CHR]l-NR6R7; wherein 3-15 membered heterocyclylC1-8alkyl and 5-14 membered heteroarylC1-8alkyl are optionally substituted with one or more substituents selected from halogen, oxo, hydroxyl, hydroxyC1-8alkyl, C1-8alkyl, – NHC(O)CH3, –NHC(O)CH2CH3 and –NHC(O)CH=CH2.; Z is CH or N; X is CH or N; R is selected from hydrogen and C1-8alkyl; at each occurrence, R2 is selected independently from halogen, –NHC(O)CH3 and – NHC(O)CH=CH2; ring A is 5-14 membered heteroaryl; at each occurrence, R3 is C1-8alkyl; R4 is selected from hydrogen and C1-8alkyl; R5 is selected from C1-8alkyl and C3-12cycloalkyl; or R4 and R5 joined together with the carbon atom to which they are attached, form a 3-15 membered heterocyclyl, C3-12cycloalkyl and 3-15 membered spirocyclyl wherein 3-15 membered heterocyclyl, C3-12cycloalkyl and 3-15 membered spirocyclyl are optionally substituted with one or more substituents selected from halogen and C1-8alkyl; ‘Y’ is absent or CR8R9; R6 is selected from hydrogen and C1-8alkyl; R7 is selected from C1-8alkyl, haloC1-8alkyl, hydroxyC1-8alkyl, C1-8alkoxyC1-8alkyl, – CH2CH2NHC(O)CH=CH2, C3-12cycloalkyl, C3-12cycloalkylC1-8alkyl and 3-15 membered heterocyclylalkyl; wherein C3-12cycloalkyl and C3-12cycloalkylC1-8alkyl is optionally substituted with C1-8alkyl and haloC1-8alkyl; R8 is hydrogen; R9 is hydrogen; R10 is selected from hydrogen and C1-8alkyl; R11 is selected independently from C1-8alkyl, haloC1-8alkyl, C6-14aryl, C6-14arylC1-8alkyl, 3-15 membered heterocyclylC1-8alkyl, C3-12cycloalkyl and C3-8cycloalkylC1-8alkyl; wherein C6- 14aryl, C6-14arylC1-8alkyl are optionally substituted with one or more substituents selected from halogen; ‘l’ is an integer ranging from 0 to 2, both inclusive; ‘m’ is an integer ranging from 0 to 4, both inclusive; ‘n’ is an integer ranging from 1 to 3, both inclusive; and ‘r’ is an integer ranging from 0 to 4, both inclusive. 2. The compound of claim 1, having represented by formula (IA) or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein, R1, R2, R3, R4, R5, R10, R11, ring A, Y, X, n, m and r are as defined in claim 1. 3. The compound of claim 1, having represented by formula (IB) or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein, R1, R2, R3, R4, R5, R10, R11, ring A, Y, n, m and r are as defined in claim 1. 4. The compound of claim 1, having represented by formula (IC) or a stereoisomer, or a pharmaceutically acceptable salt thereof, wherein, R1, R2, R3, R4, R5, R10, R11, Y, n, m and r are as defined in claim 1. 6. The compound according to any one of claims 1 to 5, wherein R2 is chloro, fluoro, – NHC(O)CH3 or –NHC(O)CH=CH2 and ‘m’ is 0 or 1. 7. The compound according to any one of claims 1 to 6, wherein R3 is methyl and ‘r’ is 1. 8. The compound according to any one of claims 1 to 7, wherein Y is absent or CH2. 9. The compound according to any one of claims 1 to 8, wherein R4 is hydrogen or CH3. 10. The compound according to any one of claims 1 to 9, wherein R5 is CH3 or cyclobutyl. 11. The compound according to any one of claims 1 to 10, wherein R4 and R5 are CH3. 12. The compound according to any one of claims 1 to 8, wherein R4 and R5 joined together 13. The compound according to any one of claims 1 to 12, wherein R10 is hydrogen or methyl. 14. The compound according to any one of claims 1 to 4, wherein R11 is methyl, ethyl, difluoromethyl, difluoroethyl, trifluoroethyl, trifluoropropyl cyclopropyl, cyclopropylmethyl, cyclopropylethyl or cyclobutylmethyl, 15. The compound according to any one of claims 1 to 3, wherein ring A , 16. The compound according to any one of claims 1 to 3, wherein ring A is . 17. The compound according to any one of claims 1, wherein ‘Z’ is C or N. 18. The compound according to any one of claims 1, wherein ‘Z’ is C. 19. The compound according to any one of claims 1-2, wherein ‘X’ is C or N. 20. The compound according to claim 1, wherein ‘Z’ is CH or N; R3 is methyl; Y is absent or CH2; R4 is hydrogen or CH3; R5 is CH3 or cyclobutyl; or R4 and R5 joined together with the carbon atom to which they are attached, form a R10 is hydrogen or methyl; R11 is methyl, ethyl, difluoromethyl, difluoroethyl, trifluoroethyl, trifluoropropyl cyclopropyl, cyclopropylmethyl, cyclopropylethyl or cyclobutylmethyl, ‘l’ is 1; ‘n’ is 1; ‘m’ is 0 or 1; and ‘r’ is 1. 21. The compound according to claim 2, wherein R3 is methyl; Y is absent or CH2; R4 is hydrogen or CH3; R5 is CH3 or cyclobutyl; or R4 and R5 joined together with the carbon atom to which they are attached, form a R10 is hydrogen or methyl; R11 is methyl, ethyl, difluoromethyl, difluoroethyl, trifluoroethyl, trifluoropropyl cyclopropyl, cyclopropylmethyl, cyclopropylethyl or ‘l’ is 1; ‘n’ is 1; ‘m’ is 0 or 1; and ‘r’ is 1. 22. The compound according to claim 3, wherein R3 is methyl; Y is absent or CH2; R4 is hydrogen or CH3; R5 is CH3 or cyclobutyl; or R4 and R5 joined together with the carbon atom to which they are attached, form a R10 is hydrogen or methyl; R11 is methyl, ethyl, difluoromethyl, difluoroethyl, trifluoroethyl, trifluoropropyl cyclopropyl, cyclopropylmethyl, cyclopropylethyl or ‘l’ is 1; ‘n’ is 1; ‘m’ is 0 or 1; and ‘r’ is 1. 23. The compound according to claim 4, wherein R2 is chloro, fluoro, –NHC(O)CH3 or –NHC(O)CH=CH2; R3 is methyl; Y is absent or CH2; R4 is hydrogen or CH3; R5 is CH3 or cyclobutyl; or R4 and R5 joined together with the carbon atom to which they are attached, form a R10 is hydrogen or methyl; R11 is methyl, ethyl, difluoromethyl, difluoroethyl, trifluoroethyl, trifluoropropyl cyclopropyl, cyclopropylmethyl, cyclopropylethyl or ‘l’ is 1; ‘n’ is 1; ‘m’ is 0 or 1; and ‘r’ is 1. 24. A compound selected from: 1-(Cyclopropylmethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-2-oxo-5- (piperidin-1-ylmethyl)-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 1-Cyclopropyl-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamide; 1-(2,2-Difluoroethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamide; (S)-1-(2,2-Difluoroethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-5-((3-methylpiperidin-1-yl)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 1-Cyclopropyl-N-(3-(3-((4-methyl-4H-1,2,4-triazol-3-yl)methyl)oxetan-3-yl)phenyl)- 2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-5- (piperidin-1-ylmethyl)-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (S)-1-(Cyclobutylmethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan- 2-yl)phenyl)-5-((3-methylpiperidin-1-yl)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; (S)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 1-(Cyclopropylmethyl)-N-(3-(3-((4-methyl-4H-1,2,4-triazol-3-yl)methyl)oxetan-3- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3-((4-methyl-4H-1,2,4-triazol-3-yl)methyl)oxetan-3-yl)phenyl)-2-oxo-5- (piperidin-1-ylmethyl)-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-2-oxo-5- (pyrrolidin-1-ylmethyl)-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5- (morpholinomethyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((4,4-Difluoropiperidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol- 3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 1-(Difluoromethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1, 2-dihydropyridine-3-carboxamide; 5-((3-Acetamidopiperidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol- 3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-1); 5-((3-Acetamidopiperidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol- 3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-2); 1-(2-Cyclopropylethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridine-3-carboxamide; (R)-5-((3-Fluoropyrrolidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol- 3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (S)-5-((3-Hydroxypyrrolidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; (S)-5-((3-Hydroxypyrrolidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; (S)-5-((3-Fluoropyrrolidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol- 3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 1-(2-Cyclopropylethyl)-N-(3-(3-((4-methyl-4H-1,2,4-triazol-3-yl)methyl)oxetan-3- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridine-3-carbox amide; (S)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-3- carboxamide; (S)-1-(Cyclopropylmethyl)-N-(3-(3-((4-methyl-4H-1,2,4-triazol-3-yl)methyl)oxetan-3- yl)phenyl)-5-((3-methylpiperidin-1-yl)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; (S)-1-(Cyclopropylmethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan- 2-yl)phenyl)-5-((3-methylpiperidin-1-yl)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; (R)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; (S)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5-((2- methylmorpholino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; (S)-1-(2-Cyclopropylethyl)-5-((3-fluoropyrrolidin-1-yl)methyl)-N-(3-(2-methyl-1-(4- methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 5-((4-Fluoropiperidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (R)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5-((2- methylmorpholino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; (S)-1-(2-Cyclopropylethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan- 2-yl)phenyl)-5-((3-methylpiperidin-1-yl)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; (S)-5-((3-Fluoropyrrolidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol- 3-yl)propan-2-yl)phenyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan- 2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((Isobutyl(methyl)amino)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5-(((oxetan-3- ylmethyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (S)-N-(2-fluoro-5-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5- ((3-methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-((3-Isopropylpiperidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-1); 5-((3-Isopropylpiperidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-2); (S)-5-((3-(hydroxymethyl)piperidin-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H- 1,2,4-triazol-3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((2-Hydroxyethyl)amino)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-(((2-Hydroxy-2-methylpropyl)amino)methyl)-N-(3-(2-methyl-1-(4-methyl-4H- 1,2,4-triazol-3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((2,2-Difluoroethyl)amino)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (S)-N-(4-fluoro-3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)phenyl)-5- ((3-methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-((4,4-Dimethyl-1,4-azasilinan-1-yl)methyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)propan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-((1s,3R)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((S)- 3-piperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3R)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-(((S)-3-methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3-carboxamide; 5-(((2-Hydroxy-2-methylpropyl)amino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl- 4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxamide; N-(2-chloro-5-((1s,3R)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-(((S)-3-methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3-carboxamide; N-(2-chloro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((1- methylcyclopropyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-((1s,3S)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((R)- 3-methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((1- methylcyclobutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((2-Ethylbutyl)amino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((3- methylbutan-2-yl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-1); N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((3- methylbutan-2-yl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-2); N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((2- methylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-1); N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((2- methylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-2); N-(3-(cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-1); N-(3-(cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-2); N-(5-(cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)-2-fluorophenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-1); N-(5-(cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)-2-fluorophenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-2); N-(3-(cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-5- (((cyclopropylmethyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-1); N-(3-(cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)phenyl)-5- (((cyclopropylmethyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-2); N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((neopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; 5-(((2-Ethoxyethyl)amino)methyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H- 1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-(((2-hydroxy-2-methylpropyl)amino)methyl)-2-oxo-1-(2,2,2- trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-(((1-methylcyclobutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-5-((tert-pentylamino)methyl)-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; 1-(Cyclopropylmethyl)-5-((isobutylamino)methyl)-N-(3-(3-methyl-1-(4-methyl-4H- 1,2,4-triazol-3-yl)cyclobutyl) phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((neopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl- 4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxamide; 1-(Cyclopropylmethyl)-N-(2-fluoro-5-(3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 5-((Ethylamino)methyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((2-Fluoro-2-methylpropyl)amino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H- 1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-chloro-5-(3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-1- (cyclopropylmethyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 1-(Cyclopropylmethyl)-5-(((cyclopropylmethyl)amino)methyl)-N-(3-(3-methyl-1-(4- methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 1-(Cyclopropylmethyl)-5-(((cyclopropylmethyl)amino)methyl)-N-(2-fluoro-5-((1s,3s)- 3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(2-chloro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((neopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-chloro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-(((cyclopropylmethyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3-carboxamide; 1-(Cyclopropylmethyl)-N-(3-(3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((neopentylamino)methyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 5-(((S)-3-Acrylamidopyrrolidin-1-yl)methyl)-N-(3-((1s,3R)-3-methyl-1-(4-methyl-4H- 1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-3-carboxamide; 1-(2-Cyclopropylethyl)-5-((isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4- methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(3-((1s,3R)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo- 5-(((S)-3-propionamidopyrrolidin-1-yl)methyl)-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2- dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((neopentylamino)methyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2- dihydropyridine-3-carboxamide; 5-(((2-Fluoro-2-methylpropyl)amino)methyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4- methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-1-(4-fluorophenyl)-5-((isobutylamino)methyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-N-(4-(3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)pyridin-2-yl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; ((S)-N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-((Isobutylamino)methyl)-N-(3-(5-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[2.3]hexan- 5-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (S)-N-(3-(5-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[2.3]hexan-5-yl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; (S)-N-(3-(3,3-difluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-difluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-N-(3-(2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan- 2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (S)-N-(3-(2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((2-Ethylbutyl)amino)methyl)-N-(3-(5-(4-methyl-4H-1,2,4-triazol-3- yl)Spiro[2.3]hexan-5-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((2- ethylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-difluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((2- ethylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(5-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[2.3]hexan-5-yl)phenyl)-5-(((2- methylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-1); N-(3-(5-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[2.3]hexan-5-yl)phenyl)-5-(((2- methylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide (Isomer-2); 5-(((Cyclopropylmethyl)amino)methyl)-N-(3-(2-(4-methyl-4H-1,2,4-triazol-3- yl)spiro[3.3]heptan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(2-fluoro-5-(5-(4-methyl-4H-1,2,4-triazol- 3-yl)spiro[2.3]hexan-5-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)-2-fluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-(5-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[2.3]hexan-5-yl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((neopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(2-chloro-5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(2-chloro-5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((neopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((neopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-3-carboxamide; 1-(Cyclopropylmethyl)-N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((neopentylamino)methyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-3- carboxamide; 1-(2,2-Difluoroethyl)-N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-Dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-((4- methyl-3-oxopiperazin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydro pyridine-3- carboxamide; 1-(2-Cyclopropylethyl)-N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-(5-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[2.3]hexan-5-yl)phenyl)-5- ((neopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-((1- methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-5-fluorophenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-((3- fluoro-3-methylazetidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-Dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(prop-2-yn-1-yl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-5-fluorophenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine-3-carboxamide; 1-(2,2-Difluoroethyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)-2-fluorophenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 1-(2,2-Difluoroethyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)-2-fluorophenyl)-5-((neopentylamino)methyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((1- methylcyclobutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 1-(Cyclopropylmethyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)-2-fluorophenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(((2- fluoro-2-methylpropyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- (((2-fluoro-2-methylpropyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; 1-(2-Cyclopropylethyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)-2-fluorophenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 1-(2-Cyclopropylethyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)-2-fluorophenyl)-5-(((2-fluoro-2-methylpropyl)amino)methyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutyl(methyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(2-fluoro-5-(2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-((((1- (fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-1-(4- fluorophenyl)-5-(isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; (S)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2- fluorophenyl)-5-((3-methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)-2-fluorophenyl)-2-oxo-1-(3,3,3-trifluoropropyl)-1,2-dihydropyridine- 3-carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-N-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(2-fluoro-5-(2-(4-methyl-4H-1,2,4-triazol- 3-yl)spiro[3.3]heptan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-1-(2,2-difluoroethyl)-N-(5-(3,3-dimethyl-1- (4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-1-(oxetan-3-ylmethyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 5-(1-(isobutylamino)ethyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-1); 5-(1-(isobutylamino)ethyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide (Isomer-2); (+)N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-5-(1- (isobutylamino)ethyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; (+)N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)- 5-(1-(isobutylamino)ethyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(5-methyl-1H-imidazol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-(3,3-dimethyl-1-(5-methyl-1H-imidazol-4-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-N-(3-(3-methyl-1-(5-methyl-1H-1,2,3-triazol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide hydrochloride; 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(5-methyl-1H-1,2,3-triazol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-N-(3-((1r,3r)-3-methyl-1-(5-methyl-1H-1,2,3-triazol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(3-acetamido-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide hydrochloride; N-(3-acrylamido-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide 2,2,2-trifluoroacetate; N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-6- ((isobutylamino)methyl)-3-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydropyrazine-2-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-1- ethyl-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 1-Ethyl-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-1-ethyl-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4- methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 5-(((3-Fluoro-3-methylbutyl)amino)methyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4- methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-1- (4-fluorophenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-1- (4-fluorobenzyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-1-methyl-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-1-(2,2-difluoroethyl)-N-(2-fluoro-5-((1s,3s)- 3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; 5-(((3-Fluoro-2,2-dimethylpropyl)amino)methyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1- (4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; 1-(2,2-Difluoroethyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- (((3-fluoro-2,2-dimethylpropyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-fluoro-5-(2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)phenyl)-5- ((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-fluoro-5-(2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)phenyl)-5- ((isopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((((1-(Fluoromethyl)cyclopropyl)methyl)amino)methyl)-N-(3-((1s,3s)-3-methyl-1- (4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1- (3,3,3-trifluoropropyl)-1,2-dihydropyridine-3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)-2-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-1-(4-fluorophenyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 1-Cyclopropyl-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-6- ((isobutylamino)methyl)-3-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydropyrazine-2-carboxamide; N-(5-(6,6-dimethyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)-2- fluorophenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(5-(6,6-dimethyl-2-(4-methyl-4H-1,2,4- triazol-3-yl)spiro[3.3]heptan-2-yl)-2-fluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(5-(6,6-dimethyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)-2- fluorophenyl)-5-((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1-(2,2,2- trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(5-(6,6-dimethyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)-2- fluorophenyl)-5-(((3-fluoro-3-methylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(5-(6,6-dimethyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)-2- fluorophenyl)-5-((isopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxamide; N-(5-(6,6-dimethyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)-2- fluorophenyl)-5-(((3-fluoro-2,2-dimethylpropyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1- (2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-((Isobutylamino)methyl)-N-(3-(6-methyl-2-(4-methyl-4H-1,2,4-triazol-3- yl)spiro[3.3]heptan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(2-fluoro-5-(6-methyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2- yl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(2-fluoro-5-(6-methyl-2-(4-methyl-4H- 1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(5-(3,3-diethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(5-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- (((3-fluoro-3-methylbutyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxamide; N-(5-(3,3-diethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; N-(2-fluoro-5-(6-methyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2- yl)phenyl)-5-((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1-(2,2,2- trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; 5-(((3-Fluoro-3-methylbutyl)amino)methyl)-N-(2-fluoro-5-(6-methyl-2-(4-methyl-4H- 1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(5-(3,3-diethyl-1-(4-methyl-4H-1,2,4- triazol-3-yl)cyclobutyl)-2-fluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; N-(5-(3,3-diethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl)-2-fluorophenyl)-5- ((isopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-(6-methyl-2-(4-methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2- yl)phenyl)-5-((isopentylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3- carboxamide; 5-(((Cyclopropylmethyl)amino)methyl)-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl- 4H-1,2,4-triazol-3-yl)cyclobutyl)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3- carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((((1-(fluoro-methyl)cyclopropyl)methyl)amino)methyl)-1-(4- fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 1-Cyclopropyl-N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-((((1-(fluoromethyl)cyclopropyl)methyl)amino)methyl)-2-oxo-1,2- dihydropyridine-3-carboxamide; 5-(((3-Fluoro-2,2-dimethylpropyl)amino)methyl)-N-(2-fluoro-5-(6-methyl-2-(4- methyl-4H-1,2,4-triazol-3-yl)spiro[3.3]heptan-2-yl)-phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3-carboxamide; N-(2-fluoro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-6-((isobutylamino)methyl)-3-oxo-4-(2,2,2-trifluoroethyl)-3,4- dihydropyrazine-2-carboxamide; or 6-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-3-oxo-4-(2,2,2-trifluoroethyl)-3,4-dihydropyrazine-2-carboxamide; and pharmaceutically acceptable salt thereof. 25. A compound of formula or a pharmaceutically acceptable salt thereof. 26. A compound of formula or a pharmaceutically acceptable salt thereof. 27. A compound of formula or a pharmaceutically acceptable salt thereof. 28. A compound of formula or a pharmaceutically acceptable salt thereof. 29. A compound of formula or a pharmaceutically acceptable salt thereof. 30. A compound of formula or a pharmaceutically acceptable salt thereof. 31. A compound of formula or a pharmaceutically acceptable salt thereof. 32. A pharmaceutical composition comprising a compound according to any one of claims 1 to 31 and a pharmaceutically acceptable excipient. 33. The pharmaceutical composition according to claim 32, wherein the pharmaceutically acceptable excipient is a carrier or diluent. 34. A method of treating or preventing from a CBL-b mediated disease, disorder, or condition in a subject comprising administering the subject in need thereof an effective amount of a compound according to any one of claims 1 to 32. 35. The method according to claim 34, wherein the disease, disorder, or condition is cancer. |
The esterification of compound of formula (1) yields ester compound of formula (2) [wherein R’ is C 1-8 alkyl]. The reaction is carried out in a suitable solvent. The suitable solvent used in the reaction may be methanol. The selective N-Alkylation of compound of formula (2) with suitable alkylating agents in the presence of suitable base and solvents yields the compound of formula (3). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from cesium carbonate, potassium carbonate, sodium carbonate, sodium hydride, etc. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from DMSO, DMF and THF. The Suzuki coupling reaction of compound of formula (3) using potassium vinyl trifluoroborate in the presence of suitable base, catalyst and solvent gives the compound of formula (4). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from potassium phosphate, potassium acetate, sodium, potassium tert-butoxide, sodium carbonate or cesium carbonate. The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction may be selected from tetrakis(triphenylphosphine)palladium(0), 1,1′-bis(diphenylphosphino)ferrocene]dichloropall adium(II) complex with dichloromethane, along with a suitable phosphine ligand, etc. The coupling reaction may be carried out in a suitable solvent or mixture thereof. The suitable solvent used in the reaction may be selected from ethanol, toluene, 1,4-dioxane, DMSO, water or a combination thereof. The compound of formula (4) upon oxidative cleavage using osmium tetra oxide and sodium periodate in a suitable mixture of solvent gives aldehyde compound of formula (5). The reaction is carried out in presence of suitable mixture of solvents. The suitable mixture of solvent may be selected from mixture of THF / water and t-BuOH. The reductive amination reaction of compound of formula (5) with appropriate amines of formula (6) using suitable reducing agent in the presence of suitable catalyst gives compound of formula (7). The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, dichloroethane, dimethylformamide, methanol, ethanol. The reaction is carried out in presence of suitable reducing agent. The suitable reducing agent used in the reaction may be selected from sodium borohydride, sodium triacetoxyborohydride and sodium cyanoborohydride. The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction may be acetic acid. The hydrolysis of compound of formula (7) gives the compound of formula (8). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from lithium hydroxide, sodium hydroxide or potassium hydroxide. The reaction is carried out in a suitable solvent. The suitable solvent used in the reaction may be selected from methanol, ethanol or tetrahydrofuran or combination thereof. The acid-amine coupling reaction of compound (8) with appropriate aromatic amines compound of formula (9) gives the compound of general formula (IA-1). The reaction is carried out in presence of suitable coupling reagents. The suitable coupling reagents used in the reaction may be selected from HATU, EDC.HCl, HOBt, DCC or T 3 P. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, THF or dimethylformamide. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from DIPEA or TEA. A general approach for the preparation of compounds of the general formula (IA-2) (wherein X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 10 , R 11 , ‘m’ and ‘r’ are as defined in the description) is depicted in synthetic scheme 2. Synthetic scheme-2: The hydrolysis reaction of compound of formula (3) [wherein R’ is C 1-8 alkyl] gives the compound of formula (10). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from lithium hydroxide, sodium hydroxide or potassium hydroxide. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from methanol, ethanol or tetrahydrofuran or combination thereof. The acid-amine coupling reaction of compound (10) with appropriate aromatic amines of compound of formula (9) gives the compound of formula (11). The reaction is carried out in a presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, THF or dimethylformamide. The reaction is carried out in a presence of suitable base. The suitable base used in the reaction may be selected from DIPEA or TEA. The reaction is carried out in a presence of suitable coupling reagents. The suitable coupling reagents used in the reaction may be selected from HATU, EDC.HCl, HOBt, DCC or T 3 P. The Suzuki coupling reaction of compound of formula (11) and potassium vinyl trifluoroborate gives the compound of formula (12). The reaction is carried out in a presence of suitable base. The suitable base used in the reaction may be selected from potassium phosphate, potassium acetate, sodium, potassium tert-butoxide, sodium carbonate or cesium carbonate. The reaction is carried out in a presence of suitable catalyst. The suitable catalyst used in the reaction may be selected from tetrakis (triphenylphosphine)palladium(0), 1,1′- bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane, along with a suitable phosphine ligand, etc. The reaction may be carried out in a suitable solvent or mixture thereof. The suitable solvent may be selected from ethanol, toluene, 1,4-dioxane, DMSO, water or a combination thereof. The compound of formula (12) upon oxidative cleavage using osmium tetra oxide and sodium periodate gives aldehyde compound of formula (13). The reaction is carried out in presence of suitable solvent or mixture thereof. The suitable solvent used in the reaction may be THF / water. The reductive amination reaction of compound of formula (13) with appropriate amines compound of formula (6) gives compound of general formula (IA-2). The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction may be acetic acid. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from TEA and DIPEA. The reaction may be carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, dimethylformamide, methanol and ethanol. The reaction is carried out in presence of suitable reducing agent. The suitable reducing agent used in the reaction may be selected from sodium borohydride, sodium triacetoxyborohydride and sodium cyanoborohydride. A general approach for the preparation of compounds of the general formula (IA-3 and IA-4) (wherein X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 10 , R 11 , ‘m’ and ‘r’ are as defined in the description) is depicted in synthetic scheme 3. Synthetic scheme-3: The Suzuki coupling reaction of compound of formula (3) [wherein R’ is C 1-8 alkyl] and potassium vinyl trifluoroborate gives the compound of formula (4). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from potassium phosphate, potassium acetate, sodium, potassium tert-butoxide, sodium carbonate or cesium carbonate. The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction may be selected from tetrakis (triphenylphosphine)palladium(0), 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane, along with a suitable phosphine ligand, etc. The reaction may be carried out in presence of suitable solvent or mixture thereof. The suitable solvent used in the reaction may be selected from ethanol, toluene, 1,4-dioxane, DMSO, water or a combination thereof. The hydrolysis reaction of compound of formula (4) in the presence of a suitable base and solvent gives the compound of formula (14). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from lithium hydroxide, sodium hydroxide or potassium hydroxide. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from methanol, ethanol or tetrahydrofuran or combination thereof. The acid-amine coupling reaction of compound (14) with appropriate aromatic amines compound of formula (9) gives the compound of formula (15). The reaction is carried out in presence of suitable coupling reagents. The suitable coupling reagents used in the reaction may be selected from HATU, EDC.HCl, HOBt, DCC or T3P. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, THF or dimethylformamide. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from DIPEA or TEA. The compound of formula (15) upon oxidative cleavage using osmium tetra oxide and sodium periodate gives aldehyde compound of formula (16). The reaction is carried out in presence of suitable solvent or mixture thereof. The suitable solvent used in the reaction may be THF / water. The reductive amination reaction of compound of formula (16) with appropriate amines (6) yields compound of formula (IA-3). The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction may be acetic acid. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from triethylamine or DIPEA. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected form dichloromethane, dichloroethane, dimethylformamide, methanol and ethanol. The reaction is carried out in presence of a suitable reducing agent. The suitable reducing agent used in the reaction may be selected from sodium borohydride, sodium triacetoxyborohydride or sodium cyanoborohydride. The treatment of compound of formula (IA-3) with suitable inorganic acid in appropriate solvent gives compound of formula (IA-4). The reaction is carried out in presence of suitable inorganic acid. The suitable inorganic acid used in the reaction may be selected from hydrochloric acid or TFA. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, dichloroethane or THF. A general approach for the preparation of compounds of the general formula (IA-5, IA- 6 and IA-7) (wherein X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 10 , R 11 , ‘m’ and ‘r’ are as defined in the description) is depicted in synthetic scheme 4. Synthetic scheme-4: The Stille coupling reaction of compound of formula (3) and tributyl(1-ethoxyvinyl)tin gives the compound of formula (17). The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction may be selected from tetrakis(triphenyl phosphine) palladium(0), dichlorobis(triphenyl phosphine)palladium(II), palladium acetate, along with a suitable phosphine ligand, etc. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from, 1,4-dioxane, DMSO or DMF. The hydrolysis reaction of compound of formula (17) gives the compound of formula (18). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from lithium hydroxide, sodium hydroxide or potassium hydroxide. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from methanol, ethanol or tetrahydrofuran or combination thereof. The acid-amine coupling reaction of compound (18) with appropriate aromatic amines compounds of formula (9) gives the compound of formula (19). The reaction is carried out in presence of suitable coupling reagents. The suitable coupling reagents used in the reaction may be selected from HATU, EDC.HCl, HOBt, DCC or T 3 P. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, THF or dimethylformamide. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from DIPEA or TEA. The reductive amination reaction of compound of formula (19) with appropriate amines compound of formula (6) yields compound of formula (IA-5). The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction may be acetic acid. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from triethylamine or DIPEA. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected form dichloromethane, dichloroethane, dimethylformamide, methanol and ethanol. The reaction is carried out in presence of a suitable reducing agent. The suitable reducing agent used in the reaction may be selected from sodium borohydride, sodium triacetoxyborohydride or sodium cyanoborohydride. The Supercritical Fluid Chromatography (SFC) purification of racemic compound of formula (IA-5) yields the compound of general formula (IA-6) and the compound general formula (IA-7). A general approach for the preparation of compounds of the general formula (IA-8) (wherein X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 10 , R 11 , ‘m’ and ‘r’ are as defined in the description) is depicted in synthetic scheme 5. Synthetic scheme-5: The acid-amine coupling reaction of compound (14) with appropriate aromatic amines compound of formula (20) [wherein Q is C or N] gives the compound of formula (21). The reaction is carried out in presence of suitable coupling reagents. The suitable coupling reagents used in the reaction may be selected from HATU, EDC.HCl, HOBt, DCC or T 3 P. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, THF or dimethylformamide. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from DIPEA or TEA. The compound of formula (21) upon oxidative cleavage using osmium tetra oxide and sodium periodate gives aldehyde compound of formula (22). The reaction is carried out in presence of suitable solvent or mixture thereof. The suitable solvent used in the reaction may be THF / water. The reductive amination reaction of compound of formula (22) with appropriate amines compound of formula (6) yields compound of formula (23). The reaction is carried out in presence of suitable catalyst. The suitable catalyst used in the reaction id acetic acid. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from triethylamine or DIPEA. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected form dichloromethane, dimethylformamide, methanol and ethanol. The reaction is carried out in presence of a suitable reducing agent. The suitable reducing agent used in the reaction may be selected from sodium borohydride, sodium triacetoxyborohydride or sodium cyanoborohydride. The compound of formula (23) on deprotection yields the compound of formula (IA-8). The reaction may be carried in presence of suitable acids. The suitable acids used in the reaction may be selected from hydrochloric acid and trifluoroacetic acid. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from methanol, ethanol, dichloroethane and 1,4- dioxane. A general approach for the preparation of compounds of the general formula (IA-9) (wherein X, Y, Z, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 10 , R 11 , ‘m’ and ‘r’ are as defined in the description) is depicted in synthetic scheme 6. Synthetic scheme-6:
The compound of formula (4) [wherein R’ is C 1-8 alkyl] upon oxidative cleavage using osmium tetra oxide and sodium periodate gives aldehyde compound of formula (5). The reaction is carried out in presence of suitable solvent or mixture thereof. The suitable solvent used in the reaction may be THF / water. The reductive amination reaction of compound of formula (5) with appropriate amines compound of formula (24) yields compound of formula (26). The reaction is carried out in presence of suitable reducing agent. The suitable reducing agent used in the reaction may be selected from sodium borohydride, sodium triacetoxyborohydride or sodium cyanoborohydride. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloro methane, dimethylformamide, methanol and ethanol. The amine compound of formula (25) upon N-protection using suitable protecting group (PG) yields the compound of formula (26). The reaction is carried out in presence of suitable protecting group. The suitable protecting group used in the reaction may be selected from di- tert-butyl dicarbonate, acetic anhydride and benzylchloroformate. The hydrolysis reaction of compound of formula (26) yields the compound of formula (27). The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from lithium hydroxide, sodium hydroxide and potassium hydroxide. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from methanol, ethanol and tetrahydrofuran or combination thereof. The acid-amine coupling reaction of compound of formula (27) with appropriate aromatic amine compound of formula (28) gives the compound of formula (29). The reaction is carried out in presence of suitable coupling reagents. The suitable coupling reagents used in the reaction may be selected from HATU, EDC.HCl, HOBt, DCC or T 3 P. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected from dichloromethane, THF or dimethylformamide. The reaction is carried out in presence of suitable base. The suitable base used in the reaction may be selected from DIPEA or TEA. The acylation reaction of compound of formula (29) yields the compound of formula (30). The reaction is carried out in presence of suitable acylating reagents. The suitable acylating reagents used in the reaction may be acetic anhydride or acryloyl chloride. The compound of formula (30) on deprotection yields the compound of formula (IA-9). The reaction is carried out in presence of suitable acid. The suitable acid used in the reaction may be selected from hydrochloric acid and trifluoroacetic acid. The reaction is carried out in presence of suitable solvent. The suitable solvent used in the reaction may be selected form dichloromethane, dichloroethane and 1,4- dioxane. EXPERIMENTAL SECTION Unless otherwise stated, work-up includes distribution of the reaction mixture between the organic and aqueous phase indicated within parentheses, separation of layers and drying the organic layer over sodium sulfate, filtration and evaporation of the solvent. Purification, unless otherwise mentioned, includes purification by silica gel chromatographic techniques, generally using ethyl acetate/petroleum ether mixture of a suitable polarity as the mobile phase. Use of a different eluent system is indicated within parentheses. The abbreviations, symbols and terms used in the examples have the following meanings throughout: INTERMEDIATES Intermediate A1 3-(2-Methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)an iline Step-1: 3-(3-Bromophenyl)-3-methylbutanoic acid To a stirred solution of bromobenzene (10 g, 0.0183 mmol) in DCM (100 mL) was added 3,3 dimethyl acrylic acid (3.19 g, 0.0318 mol). To this reaction mixture AlCl 3 was added portion wise at 15-20 o C and stirred at room temperature for 90 min. The reaction mixture was quenched with 1 N HCl and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by SFC to get 3.1 g of the desired NMR (400 MHz, DMSO-d 6 ) δ 1.36 (s, 6H), 2.60 (s, 2H), 7.24 - 7.28 (m, 1H), 7.36 - 7.41 (m, 2H), 7.53 (s, 1H), 11.9 (brs, 1H). Step-2: 2-(3-(3-Bromophenyl)-3-methylbutanoyl)-N-methylhydrazine carbothioamide H H O Br To a stirred solution of 3-(3-bromophenyl)-3-methylbutanoic acid (6.2 g, 0.024 mol) in DMF (60 mL) was added HATU (11 g, 0.029 mol) and stirred at room temperature for 30 min. To this mixture was added DIPEA (12.5 mL, 0.072 mol) and 4-methylthiosemicarbazide (2.8 g, 0.0265 mmol) and stirred at room temperature for 18 h. The reaction mixture was diluted with water and stirred for 30 min. The solid obtained was filtered and dried under vacuum to yield 4.83 g of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.36 (s, 6H), 2.50 (s, 2H), 2.83 (s, 3H), 7.26-7.30 (m, 1H), 7.39-7.41 (m, 3H), 7.53 (brs, 1H), 9.19 (brs, 1H), 9.60 (brs, 1H). Step-3: 3-(2-(3-Bromophenyl)-2-methylpropyl)-4-methyl-1H-1,2,4-triaz ole-5(4H)-thione To a stirred solution of 2-(3-(3-bromophenyl)-3-methylbutanoyl)-N-methylhydrazine carbothioamide (4.8 g, 0.0139 mol) in 1 N NaOH (170 mL) was stirred at room temperature for 18 h. The reaction mixture was acidified using 3N HCl and stirred for 15 min. The precipitated solid was filtered, washed with excess water and dried under vacuum to yield 4.31 g of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.40 (s, 6H), 3.03 (s, 2H), 3.13 (s, 3H), 7.23- 7.27 (m, 1H), 7.33-7.40 (m, 2H), 7.48-7.56 (m, 1H), 13.45 (s, 1H), ESI-MS (m/z) 327 (M+2H) + Step-4: 3-(2-(3-Bromophenyl)-2-methylpropyl)-4-methyl-4H-1,2,4-triaz ole To a stirred solution of 3-(2-(3-bromophenyl)-2-methylpropyl)-4-methyl-1H-1,2,4-triaz ole- 5(4H)-thione (4.31 g, 0.013 mol) in DCM / acetic acid (2:1, 130 mL) was added 50 % solution of H 2 O 2 (4.3 mL) and stirred at 0° C for 1 h. The reaction mixture was concentrated under reduced pressure. The residue obtained was triturated with diethyl ether, filtered and dried to obtain 4.2 g of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.42 (s, 6H), 3.26 (s, 2H), 3.51 (s, 3H), 7.26-7.30 (m, 1H), 7.38-7.45 (m, 2H), 7.58-7.59 (m, 1H), 9.28 (s, 1H); ESI-MS (m/z) 294 (M+H) + Step-5: 3-(2-Methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)an iline In a sealed tube, to a stirred solution of 3-(2-(3-bromophenyl)-2-methylpropyl)-4-methyl-4H- 1,2,4-triazole (1 g, 0.0034 mol) in NMP (10 mL) were added aq. NH 3 (10 mL), Copper (I) oxide (194 mg 1.359 mmol) and stirred at 90° C for 16 h. The reaction mixture was concentrated under reduced pressure. The residue obtained was triturated with diethyl ether to give 641 mg of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.33 (s, 6H), 2.50 (s, 2H), 3.05 (s, 3H), 4.92 (brs, 2H), 6.37 - 6.42 (m, 2H), 6.49 (s, 1H), 6.88-6.92 (m, 1H), 8.22 (s, 1H); ESI-MS (m/z) 231.2 (M+H) + Intermediate A2 2-Fluoro-5-(2-Methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propa n-2-yl)aniline Step-1: Diethyl 2-(2-(3-bromo-4-fluorophenyl)propan-2-yl)malonate To a stirred solution of 2-bromo-4-iodo-1-fluorobenzene (5.86 g, 19.5 mmol) in THF (15 mL) at -10 o C was added dropwise 2M solution of isopropyl magnesium chloride in THF (11.25 mL, 22.5 mmol) and stirred at 0 o C for 30 min and further stirred at room temperature for 1 hr. To this mixture at 0 o C was added copper (I) iodide (860 mg, 4.5 mmol) and stirred for 10 min and then added diethyl isopropylidene malonate (3 g, 15 mmol). The reaction mixture was heated to 60 o C for 2 h. The reaction mixture was quenched with 1 N HCL and diluted with ethyl acetate. The suspension obtained was filtered and washed with ethyl acetate. The filtrate obtained was extracted with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by flash chromatography to get 3.5 g of the desired product. 1 H NMR (400 MHz, CDCl 3 ): δ 1.17 (t, J= 7.2 Hz, 6H), 1.57 (s, 6H), 3.73 (s, 1H), 4.10 (q, J=6.8 Hz, 4H), 7.04-7.09 (m, 1H), 7.30 - 7.33 (m, 1H), 7.55-7.57 (m, 1H); ESI-MS (m/z) 375.0 (M+H) + Step-2: Ethyl 3-(3-bromo-4-fluorophenyl)-3-methylbutanoate To a stirred suspension of diethyl 2-(2-(3-bromo-4-fluoro phenyl)propan-2-yl)malonate (2.4 g, 6.39 mmol), lithium chloride (600 mg, 14.04 mmol) and water (114 mg, 6.39 mmol) in DMSO (12 mL) was subjected to microwave irradiation for 1 h at 200 o C. The reaction mixture was diluted with water and extracted thrice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by flash chromatography to get 1.5 g of desired product. 1 H NMR (400 MHz, CDCl 3 ): δ 1.12 (t, J= 7.2 Hz, 3H), 1.45 (s, 6H), 2.60 (s, 2H), 4.01 (q, J=7.2 Hz, 2H), 7.04-7.09 (m, 1H), 7.27-7.30 (m, 1H), 7.53-7.55 (m, 1H); ESI-MS (m/z) 303.1 (M+H) + 3-(3-Bromo-4-fluorophenyl)-3-methylbutanehydrazide To a stirred solution of ethyl 3-(3-bromo-4-fluorophenyl)-3-methylbutanoate (1.5 g, 4.95 mmol) in MeOH (7 mL) at 0° C was added dropwise 99% hydrazine hydrate (7 mL). The reaction mixture was warmed to room temperature and heated to 90°C for 16 h. The mixture was concentrated and the obtained residue was dissolved in ethyl acetate. The organic layer was washed with water, brine solution and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to yield 1.4 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.33 (s, 6H), 2.33 (s, 2H), 4.10 (brs, 2H), 7.25-7.30 (m, 1H), 7.38-7.42 (m, 1H), 7.60-7.62 (m, 1H), 8.87 (brs, 1H); ESI-MS (m/z) 290.1 (M+2H) + Step-4: 2-(3-(3-Bromo-4-fluorophenyl)-3-methylbutanoyl)-N-methylhydr azinecarbothioamide . To a stirred solution of 3-(3-bromo-4-fluorophenyl)-3-methylbutanehydrazide (1.4 g, 4.62 mmol) in THF (10 mL) at 0°C was added dropwise methylisothiocyanate (1 g, 13.86 mmol). The reaction mixture was stirred at room temperature for 1h and heated to 80° C for 3 h. The mixture was concentrated under reduced pressure and the residue obtained was triturated with pentane. The solid obtained was filtered and dried under vacuum to yield 1.6 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.36 (s, 6H), 2.40 (s, 2H), 2.82 (d, J= 4.0 Hz, 3H), 7.27-7.31 (m, 1H), 7.40-7.43 (m, 1H), 7.54 (s, 1H), 7.62-7.64 (m, 1H), 9.18 (s, 1H), 9.59 (s, 1H); ESI-MS (m/z) 363.1 (M+2H) + Step-5: 5-(2-(3-Bromo-4-fluorophenyl)-2-methylpropyl)-4-methyl-4H-1, 2,4-triazole-3-thiol To a stirred solution of 2-(3-(3-Bromo-4-fluorophenyl)-3-methylbutanoyl)-N- methylhydrazinecarbothioamide (1.4 g, 3.86 mmol) in 1 N NaOH (30 mL) was stirred at room temperature for 16 h. The reaction mixture was acidified using 2N HCL and stirred for 15 min. The precipitated solid was filtered, washed with excess water and dried under vacuum to yield 1.3 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.39 (s, 6H), 3.04 (s, 2H), 3.19 (s, 3H), 7.25-7.30 (m, 1H), 7.38-7.42 (m, 1H), 7.67-7.69 (m, 1H), 13.44 (brs, 1H); ESI-MS (m/z) 345.0 (M+2H) + 3-(2-(3-Bromo-4-fluorophenyl)-2-methylpropyl)-4-methyl-4H-1, 2,4-triazole To a stirred solution of 5-(2-(3-Bromo-4-fluorophenyl)-2-methylpropyl)-4-methyl-4H-1, 2,4- triazole-3-thiol (1.3 g, 3.63 mmol) in DCM (30 mL) and AcOH (3 g, 50.83 mmol) at 0°C was added 30% H2O2 solution (370 mg, 10.89 mmol). The mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with water and extracted twice with DCM. The solvent was evaporated under reduced pressure and the solid obtained was purified by silica gel column chromatography to yield 900 mg of the desired product. 1 HNMR (400 MHz, DMSO- d6): δ 1.40 (s, 6H), 2.99 (s, 2H), 3.25 (s,3H), 7.24-7.28 (m, 1H), 7.32-7.36 (m, 1H), 7.58-7.60 (m,1H), 8.25 (s, 1H); ESI MS (m/z) 313.1 (M+2H) + Step-7: 2-Fluoro-5-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propa n-2-yl)aniline In a sealed tube, to a stirred solution of 3-(2-(3-Bromo-4-fluorophenyl)-2-methylpropyl)-4- methyl-4H-1,2,4-triazole (400 mg, 1.28 mmol) in NMP (4 mL) was added aqueous NH 3 (4 mL), copper(I) oxide (73 mg, 0.512 mmol) and stirred at 90° C for 16 h. The reaction mixture was quenched with water and extracted thrice with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and the solvent was evaporated under vacuum to give 300 mg of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.34 (s, 6H), 2.87 (s, 2H), 3.09 (s, 3H), 4.99 (s, 2H), 6.39-6.43 (m, 1H), 6.68-6.71 (m, 1H), 6.82-6.87 (m, 1H), 8.22 (s, 1H); ESI-MS (m/z) 249.2 (M+H) + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-1. Table-1: Structure, Name and analytical data of intermediate (A3) Intermediate A4 3-(3-((4-Methyl-4H-1,2,4-triazol-3-yl)methyl)oxetan-3-yl)ani line Step-1: Ethyl 2-(oxetan-3-ylidene)acetate To a stirred solution of NaH (611 mg, 15.27 mmol) in THF (25 mL) was added ethyl 2- (diethoxyphosphoryl)acetate ( 3.422 mg, 15.27 mmol) dropwise for 10-15 min at 0 o C and further stirred at room temperature for 30 min followed by the addition of oxetan-3-one (1 g, 13.889 mmol). The mixture was stirred for 18 h. The reaction mixture was quenched with aqueous NaHCO 3 solution and extracted twice with Ethyl acetate. The organic layer was separated, dried over sodium sulphate and concentrated. The residue obtained was purified by silica gel chromatography to yield 1.2 g of the desired product. 1 H NMR (400 MHz, CDCl 3 ) δ 1.28 (t, J = 7.2 Hz, 3H), 4.13-4.21 (m, 2H), 5.31 - 5.33 (m, 2H), 5.51-5.54 (m, 2H), 5.64-5.66 (m, 1H). Step-2: Ethyl 2-(3-(3-bromophenyl)oxetan-3-yl)acetate To a degassed solution of [Rh(COD)Cl] 2 (170 mg, 0.352 mmol) in dioxane (15 mL) was added 1.5 aqueous KOH (6 mL) dropwise at room temperature and stirred for 30 min. To this mixture was added drop wise solution of ethyl 2-(oxetan-3-ylidene)acetate (1g, 7.042 mmol) in dioxane (10 mL) followed by (3-bromo phenyl)boronic acid (2 g, 10.56 mmol) in dioxane (10 mL) solution and stirred for 1 hr. The reaction was stirred for 1 h and to this reaction mixture (3- bromophenyl)boronic acid (700 mg, 3.521 mmol) was again added and stirred at room temperature for 48 h. The mixture was quenched with brine solution and extracted thrice with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography to yield 1.3 g of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.04 (t, J = 7.2 Hz, 3H), 2.50-2.52 (m, 2H), 3.92 (q, J = 6.8 Hz, 2H), 4.75 (d, J = 6.4 Hz, 2H), 4.79 (d, J = 6.4 Hz, 2H), 7.28-7.32 (m, 2H), 7.45-7.46 (m, 2H). Step-3: 2-(3-(3-Bromophenyl)oxetan-3-yl)acetic acid To a stirred solution of ethyl 2-(3-(3-bromophenyl)oxetan-3-yl)acetate (150 mg, 0.5 mmol) in THF (1.5 mL) was added aqueous solution of LiOH (40 mg , 1 mmol) at 0 o C and stirred at room temperature for 4 h. The solvent was removed and acidified using 1 N HCl. The aqueous layer was extracted twice with ethyl acetate and dried over sodium sulphate. The organic layer was concentrated to yield 140 mg of the desired product. 1 H NMR (400 MHz, DMSO) δ 3.09 (s, 2H), 4.74-4.78 (m, 4H), 7.32 (d, J = 4.8 Hz, 2H), 7.44-7.49 (m, 2H), 12.24 (brs, 1H) Step-4: 2-(2-(3-(3-Bromophenyl)oxetan-3-yl)acetyl)-N-methylhydrazine carbothioamide To a stirred solution of 2-(3-(3-bromophenyl)oxetan-3-yl)acetic acid (135 mg, 0.498 mmol) in DMF (1.5 mL) was added HATU (227 mg, 0.597 mmol) and stirred for 15 min. To the reaction mixture was added N-methylhydrazinecarbothioamide (57 mg, 0.547 mmol) and DIPEA (192 mg, 1.494 mmol) and stirred at room temperature for 18 h. The reaction mixture was quenched with water and extracted thrice with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography to yield 145 mg of the desired product. 1 H NMR (400 MHz, DMSO) δ 2.51 (d, J = 4.8 Hz, 3H), 3.00 (s, 2H), 4.74-4.81 (m, 4H), 7.29-7.31 (m, 2H), 7.43-7.48 (m, 2H), 7.6 (brs, 1H), 9.14 (s, 1H), 9.70 (s, 1H); ESI-MS (m/z) 359.9 (M+2H) + Step-5: 3-((3-(3-Bromophenyl)oxetan-3-yl)methyl)-4-methyl-1H-1,2,4-t riazole-5(4H)-thione To a stirred solution of 2-(2-(3-(3-bromophenyl)oxetan-3-yl)acetyl)-N- methylhydrazinecarbothioamide (100 mg, 0.28 mmol) in 1N NaOH (3.5 mL) was stirred at room temperature for 18 h. The mixture was cooled and neutralized using 1N HCl. The solid obtained was filtered and dried under vacuum to give 65 mg of the desired product. 1 H NMR (400 MHz, DMSO-d6) δ 3.01 (s, 3H), 3.53 (s, 2H), 4.78 - 4.82 (m, 4H), 7.17 (d, J = 7.6 Hz, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.44 -7.46 (m, 2H), 13.49 (brs, 1H); ESI-MS (m/z) 340.2 (M+H) + Step-6: 3-((3-(3-Bromophenyl)oxetan-3-yl)methyl)-4-methyl-4H-1,2,4-t riazole To a stirred solution of 3-((3-(3-bromophenyl)oxetan-3-yl)methyl)-4-methyl-1H-1,2,4-t riazole- 5(4H)-thione (350 mg, 1.032 mmol) in water (1.5 mL) was added NaNO 2 (750 mg, 10.32 mmol) followed by dropwise addition of 1N HNO3 (3.5 ml) at 0 o C and stirred for 1 h. The reaction mixture was quenched with saturated solution of NaHCO 3 and extracted thrice with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated. The residue obtained was purified by silica gel chromatography to yield 245 mg of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 3.02 (s, 3H), 3.49 (s, 2H), 4.81 (d, J = 6 Hz, 2H), 4.89 (d, J = 6 Hz, 2H), 7.00 (d, J = 7.6 Hz, 1H), 7.24 (m, 2H), 7.41 (d, J = 7.6 Hz, 1H), 8.23 (s, 1H); ESI-MS (m/z) 309.9 (M+H) + Step-7: 3-(3-((4-Methyl-4H-1,2,4-triazol-3-yl)methyl)oxetan-3-yl)ani line In a sealed tube, to a stirred solution of 3-((3-(3-bromophenyl)oxetan-3-yl)methyl)-4-methyl- 4H-1,2,4-triazole (200 mg, 0.629 mmol) in NMP (2 mL) were added aqueous NH 3 (2 mL), Copper (I) oxide (35mg, 0.2515 mmol) and stirred at 90° C for 16 h. The reaction mixture was quenched with water and extracted thrice with ethyl acetate. The organic layer was evaporated under vacuum to give 160 mg of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 2.83 (s, 3H), 3.39 (s, 2H), 4.75 (d, J = 6 Hz, 2H), 4.85 (d, J = 6 Hz, 2H), 5.02 (brs.2H), 5.92 (d, J = 7.2 Hz, 1H),6.04 (s, 1H), 6.39 - 6.41 (m, 1H), 6.89 (d, J = 8 Hz, 1H), 8.21 (brs, 1H); ESI-MS (m/z) 245.2 (M+H) + Intermediate A5 3-((1s,3s)-3-Methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclob utyl)aniline Step-1: 1,3-Dibromo-2-methylpropane Br Br To a stirred solution of 2-methyl-1,3-propanediol (20 g, 222 mmol) and triphenyl phosphine (128.1 g, 488.3 mmol) in DCM (500 mL) was added N-Bromosuccinimide (86.92 g, 488.35mmol) portion wise at 0°C and stirred at room temperature for 16 h. The solvent was concentrated under reduced pressure and the residue obtained was purified by silica gel chromatography to yield 23.4 g of the desired product. 1 HNMR (400 MHz, CDCl 3 ): δ 1.17 (d, J = 6.4 Hz, 3H), 2.18-2.24 (m, 1H), 3.46-3.56 (m, 4H). Step-2: 1-(3-Bromophenyl)-3-methylcyclobutanecarbonitrile To a stirred suspension of NaH (60% suspension in mineral oil) (2.58g, 107.65 mmol) in DMF (100 mL) was added dropwise solution of 3-bromophenylacetonitrile (10.55 g, 53.826 mmol) at 0°C followed by slow addition of 1,3-dibromo-2-methylpropane (11.62 g, 53.826 mmol). The reaction mixture was stirred at room temperature for 2 h and at 80° C for 16 h. The reaction mixture was cooled to 0°C and quenched with aqueous NH 4 Cl solution. The aqueous layer was extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous Na 2 SO4 and concentrated. The residue obtained was purified by silica gel column chromatography to yield 9.15 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.22 (d, J=6 Hz, 3H), 2.18-2.23(m, 1H), 2.45-2.51(m, 2H), 2.77-2.82 (m, 2H), 7.40-7.45 (m, 1H), 7.54-7.71 (m, 2H), 7.72 (d, J = 1.6 Hz, 1H). 1-(3-Bromophenyl)-3-methylcyclobutanecarboxylic acid To a stirred solution of 1-(3-bromophenyl)-3-methylcyclobutanecarbonitrile (17.7 g, 70.76 mmol), in 80 mL of AcOH/H 2 O (1:1) was added Conc. H 2 SO 4 (40 mL) dropwise at 0° C and stirred at 0° C for 15 min and heated to 120° C for 16 h. The reaction mixture was cooled to room temperature and quenched with water and extracted twice with ethyl acetate. The organic layer was washed with brine solution, dried over anhydrous Na 2 SO4 and concentrated to give 18 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.06 (d, J=6.4 Hz, 3H), 2.13- 2.19 (m, 1H), 2.32 (t, J=5.2 Hz, 2H), 2.51-2.61 (m, 2H),), 7.31-7.39 (m, 2H), 7.42-7.50 (m, 2H), 12.47 (brs, 1H) Step-4: Methyl 1-(3-bromophenyl)-3-methylcyclobutanecarboxylate To a stirred solution of 1-(3-bromophenyl)-3-methylcyclobutanecarboxylic acid (18.3 g, 67.99 mmol) in MeOH (180 mL) was added conc. H 2 SO 4 (18 mL) and stirred at room temperature for 2 h and heated to 90° C for 16 h. The reaction mixture was concentrated under vacuum and diluted with ethyl acetate. The organic layer was washed with water, brine solution and dried over anhydrous Na2SO4. The solvent was evaporated under vacuum to obtain 19.1 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.15 (d, J = 6.8 Hz, 3H), 2.26-2.30 (m, 1H), 2.41-2.46 (m, 2H), 2.66-2.69 (m, 2H), 3.51 (s, 3H), 7.17-7.28 (m, 1H), 7.34-7.41 (m, 2H), 7.56 (d, J = 2 Hz, 1H). Step-5: 1-(3-Bromophenyl)-3-methylcyclobutanecarbohydrazide To a stirred solution of Methyl 1-(3-bromophenyl)-3-methylcyclobutanecarboxylate (19.1 g, 67.45 mmol) in MeOH (95 mL) was added 99% hydrazine hydrate (95 mL) at 0°C. The reaction mixture was warmed to room temperature and heated to 90°C for 16 h. The mixture was concentrated and the obtained residue was dissolved with ethyl acetate. The organic layer was washed with water, brine solution and dried over anhydrous sodium sulfate. The solvent was evaporated unde reduced pressure to yield 19.18 g of the desired product. ESI-MS (m/z) 283.1 (M+H) + Step-6: 2-(1-(3-Bromophenyl)-3-methylcyclobutanecarbonyl)-N-methylhy drazinecarbothio amide To a stirred solution of 1-(3-bromophenyl)-3-methylcyclobutanecarbohydrazide (19.0 g, 67.09 mmol) in THF (200 mL) was added dropwise methylisothiocyanate (14.71 g, 201.3 mmol) at 0°C. The reaction mixture was stirred at room temperature for 1h and heated to 80° C for 3 h. The mixture was concentrated under reduced pressure and the residue obtained was triturated with pentane. The solid obtained was filtered and dried under vacuum to yield 23.8 g of the desired product. ESI-MS (m/z) 356.0 (M+H) + 5-(1-(3-Bromophenyl)-3-methylcyclobutyl)-4-methyl-2,4-dihydr o-3H-1,2,4-triazole- 3-thione To a stirred solution of 2-(1-(3-bromophenyl)-3-methylcyclobutanecarbonyl)-N- methylhydrazinecarbothioamide (23.4 g, 65.67 mmol) in 1N NaOH (500 mL) was stirred at room temperature for 16 h. The reaction mixture was acidified using 2N HCl and stirred for 15 min. The precipitated solid was filtered, washed with excess water and dried under vacuum to yield 20.18 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.06 (d, J =6.0 Hz, 3H), 2.45-2.51 (m, 3H), 2.76 (d, J =3.6 Hz, 2H), 3.01 (s, 3H), 7.35-7.39 (m, 2H), 7.51-7.54 (m, 2H), 13.7 (brs, 1H); ESI-MS (m/z) 338.0 (M+H) + Step-8: 3-((1s,3s)-1-(3-Bromophenyl)-3-methylcyclobutyl)-4-methyl-4H -1,2,4-triazole To a stirred solution of 5-(1-(3-bromophenyl)-3-methylcyclobutyl)-4-methyl-2,4-dihydr o-3H- 1,2,4-triazole-3-thione (10 g, 19.56 mmol) in DCM (240 mL) and AcOH (40 mL) was added 30% H 2 O 2 solution at 0°C. The mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with water and extracted twice with DCM. The solvent was evaporated under reduced pressure and the solid obtained was purified by silica gel column chromatography to yield racemic 4.8 g of the desired product. The racemic product obtained was purified by SFC purification to yield cis isomer 2.65 g of the desired product. 1 HNMR (400 MHz, CDCl 3 ): δ 1.16 (d, J = 5.6 Hz, 3H), 2.64-2.70(m, 3H), 2.82-2.85(m, 2H), 3.23 (s, 3H), 7.23-7.29 (m, 1H), 7.40-7.43 (m, 2H), 7.56 (d, J = 1.6Hz, 1H), 8.19 (s, 1H); ESI MS (m/z) 306.0 (M+H) + Step-9: 3-((1s,3s)-3-Methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclob utyl)aniline In a sealed tube, to a stirred solution of 3-((1s,3s)-1-(3-bromophenyl)-3-methylcyclobutyl)-4- methyl-4H-1,2,4-triazole (250 mg, 0. 816 mmol) in NMP (3.5 mL) was added aqueous NH 3 (3.5 mL), copper oxide (47 mg, 0.326 mmol) and stirred at 90° C for 16 h. The reaction mixture was quenched with water and extracted thrice with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and the solvent was evaporated under vacuum to give 171 mg of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.05 (d, J= 4.8 Hz, 3H), 2.46 – 2.51 (m, 3H), 2.71 (d, J=7.2 Hz, 2H), 3.16 (s, 3H), 5.06 (brs, 2H), 6.41 – 6.46 (m, 3H), 6.78 (t, J = 7.6 Hz, 1H), 8.39 (brs, 1H); ESI-MS (m/z)243.2(M+H) + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-2. Table-2: Structure, Name and analytical data of intermediate (A6-A9) Intermediate-A10 2-Chloro-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)aniline To a stirred solution of 3-((1s,3s)-1-(3-bromo-4-chlorophenyl)-3-methylcyclobutyl)-4- methyl- 4H-1,2,4-triazole (50 mg, 0.147 mmol) in ethanol (1.0 mL) and water (0.75mL) was degassed for 10 min. The NaN 3 (19 mg, 0.294mmol), CuI (28mg, 0.147 mmol), trans N,N-dimethyl-1,2- cyclohexanediamine (17 mg,0.147mmol) and sodium ascorbate (58mg, 0.294mmol) were added to the reaction mixture and stirred at 110°C for 18 h in a sealed tube. The reaction mixture was quenched with water and extracted thrice with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and the solvent was evaporated. The residue obtained purified by column chromatography to give 21 mg of the desired product. 1 H NMR (400 MHz, DMSO- d6) δ 1.05 (d, J = 5.6 Hz, 3H), 2.43-2.51(m, 3H), 2.68 (m, 2H), 3.16 (s, 3H), 5.35 (s, 2H), 6.50 (dd, J 1 = 2.4 Hz, J 2 =8.4 Hz, 1H), 6.72 (d, J=2.4 Hz, 1H), 7.15 (d, J=8.4Hz, 1H), 8.29 (s,1H); ESI-MS (m/z) 278 (M+2H) + Intermediate-A11 3-(3,3-Dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl )aniline Step-1: 2,2-Dimethylpropane-1,3-diyldimethanesulfonate MsO OMs To a stirred solution of 2,2-dimethylpropane-1,3-diol (10 g, 96.1 mmol) in DCM (100 mL) triethylamine (33.7 mL, 240 mmol) was added. The mesyl chloride (18.5 mL, 240 mmol) was added dropwise at 0°C and stirred at room temperature for 16 h. The reaction mixture was quenched with water and extracted twice with DCM. The organic layer was washed with brine solution, dried over anhydrous Na 2 SO 4 and concentrated to give 11.0 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 0.86 (s, 6H), 3.18 (s, 6H), 4.00 (s, 4H). Step-2: 1,3-Diiodo-2,2-dimethylpropane To a stirred solution of 2,2-dimethylpropane-1,3-diyldimethanesulfonate (2.0 g, 7.69 mmol) in DMF (20 mL) was added KI (5.1 g, 30.7 mmol) portion wise at 0°C and stirred at 120°C for 16 h. The reaction mixture was cooled to room temperature and quenched with water and extracted twice with petroleum ether. The organic layer was washed with brine solution, dried over anhydrous Na 2 SO 4 and concentrated to give 2.1 g of the desired product. 1 HNMR (400 MHz, CDCl 3 ): δ 1.26 (s, 6H), 3.28 (s, 4H). Step-3: 1-(3-Bromophenyl)-3,3-dimethylcyclobutane-1-carbonitrile To a stirred suspension of NaH (60% suspension in mineral oil) (734 mg, 15.3 mmol) in DMF (15 mL) was added dropwise solution of 3-bromophenylacetonitrile (1.0 g, 5.10 mmol) and 1,3- diiodo-2,2-dimethylpropane (2.1 g, 6.63 mmol) in DMF (5 mL) at 0°C and dropwise addition was continued for 1h. The reaction mixture was stirred at RT for 2 h and then at 80°C for 16 h. The reaction mixture was cooled to 0°C and quenched with ice cold water solution. The aqueous layer was extracted twice with petroleum ether. The organic layer was separated, dried over anhydrous Na 2 SO4 and concentrated. The residue obtained was purified by silica gel column chromatography to yield 700 mg of the desired product. 1 HNMR (400 MHz, CDCl 3 ): δ 1.16 (s, 3H), 1.50 (s, 3H), 2.47 (d, J=13.2 Hz, 2H), 2.74 (d, J=12.4 Hz, 2H), 7.26 – 7.28 (m, 1H), 7.33 – 7.35 (m, 1H), 7.45-7.47 (m, 1H), 7.54 (s, 1H). Step-4: 1-(3-Bromophenyl)-3,3-dimethylcyclobutane-1-carboxylic acid H OOC Br To a stirred solution of 1-(3-bromophenyl)-3,3-dimethylcyclobutane-1-carbonitrile (700 mg, 2.66 mmol), in 4.2 mL of AcOH/H 2 O (1:1) was added conc. H 2 SO 4 (2.1 mL) dropwise at 0° C and stirred at 0° C for 15 min and heated to 120° C for 16 h. The reaction mixture was cooled to room temperature, quenched with water and extracted twice with ethyl acetate. The organic layer was washed with brine solution, dried over anhydrous Na2SO4 and concentrated to give 700 mg of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 0.97 (s, 3H), 1.12 (s, 3H), 2.25 (d, J=12.8 Hz, 2H), 2.63 (d, J=12.8 Hz, 2H), 7.26-7.33 (m, 2H), 7.39-7.45 (m, 2H), 12.50 (brs, 1H), ESI-MS (m/z) 281.1(M-H) + Step-5: 2-(1-(3-Bromophenyl)-3,3-dimethylcyclobutane-1-carbonyl)-N-m ethylhydrazine-1- carbothioamide To a stirred solution of 1-(3-bromophenyl)-3,3-dimethylcyclobutane-1-carboxylic acid (700 mg, 2.47 mmol) in DMF (8.0 mL) was added DIPEA (1.3 mL, 7.42 mmol) and HATU (1.1 g, 2.96 mmol) stirred for 30 min.4 methylthiosemicarbazide (313 mg, 2.96 mmol) was added at 0°C. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with water and extracted twice with EtOAc. The solvent was evaporated under reduced pressure and the solid obtained was purified by silica gel column chromatography to yield 820 mg of the desired product. ESI-MS (m/z) 371.1 (M+2H) + 5-(1-(3-Bromophenyl)-3,3-dimethylcyclobutyl)-4-methyl-2,4-di hydro-3H-1,2,4- triazole-3-thione To a stirred solution of 2-(1-(3-bromophenyl)-3,3-dimethylcyclobutane-1-carbonyl)-N- methylhydrazine-1-carbothioamide (820 mg, 2.21 mmol) in 1N NaOH (8.0 mL) was stirred at room temperature for 16 h. The reaction mixture was acidified using 6N HCl and stirred for 2 h. The precipitated solid was filtered, washed with excess water and dried under vacuum to yield 760 mg of the desired product. ESI-MS (m/z) 353.1 (M+2H) + Step-7: 3-(1-(3-Bromophenyl)-3,3-dimethylcyclobutyl)-4-methyl-4H-1,2 ,4-triazole To a stirred solution of 5-(1-(3-bromophenyl)-3,3-dimethylcyclobutyl)-4-methyl-2,4-di hydro- 3H-1,2,4-triazole-3-thione (760 mg, 2.16 mmol) in DCM (10.0 mL) and AcOH (2.2 mL) was added 30% H 2 O 2 solution (0.9 mL) at 0°C. The mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water and extracted twice with DCM. The solvent was evaporated under reduced pressure and the solid obtained was purified by silica gel column chromatography to yield 628 mg of the desired product. 1 HNMR (400 MHz, CDCl3): δ 1.03 (s, 3H), 1.09(s, 3H), 2.57 (d, J = 12.8 Hz, 2H), 2.87(d, J = 10.4 Hz, 2H), 3.22 (s, 3H), 7.32-7.35 (m, 3H), 7.42-7.45 (m, 1H), 8.33 (s, 1H); ESI MS (m/z) 321.1 (M+2H) + Step-7: 3-(3,3-Dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl )aniline In a sealed tube, to a stirred solution of 3-(1-(3-bromophenyl)-3,3-dimethylcyclobutyl)-4- methyl-4H-1,2,4-triazole (628 mg, 1.96 mmol) in ACN (8.0 mL) was added aqueous NH 3 (4.0 mL), copper(I)oxide (280 mg, 1.96 mmol) and stirred at 100°C for 16 h. The reaction mixture was quenched with water and ethyl acetate, filtered and filtrate obtained was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and solvent was evaporated under reduced pressure and the solid obtained was purified by silica gel column chromatography to yield 410 mg of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 1.03 (s, 3H), 1.11 (s, 3H), 2.48 (d, J = 12.8 Hz, 2H), 2.80 (d, J = 12.4 Hz, 2H), 3.19 (s, 3H), 5.07 (brs, 2H), 6.38-6.43 (m, 3H), 6.97 (t, J = 7.6 Hz, 1H), 8.29 (s, 1H); ESI-MS (m/z) 257.2 (M+H) + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-3. Table-3: Structure, Name and analytical data of intermediate (A12-A19) Intermediate A20 3-(3,3-Difluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl )aniline Step-1: 1-(3-Bromophenyl)-3,3-dimethoxycyclobutane-1-carbonitrile To a stirred suspension of NaH (60% suspension in mineral oil) (2.56g, 63.77 mmol) in DMF (50 mL) was added dropwise solution of 3-bromophenylacetonitrile (5.0 g, 25.51 mmol) at 0°C. The reaction mixture was stirred at 0°C for 30min, followed by slow addition of 1,3-dibromo- 2,2-Dimethoxy-propane (5.32 g, 20.40 mmol). The reaction mixture was stirred at room temperature for 2 h and at 60°C for 48 h. The reaction mixture was cooled to 0°C and quenched with water. The aqueous layer was extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous Na 2 SO4 and concentrated. The residue obtained was purified by silica gel column chromatography to yield 2.4 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 2.72 (d, J=13.6 Hz, 2H), 3.12(d, J= 13.6Hz, 2H), 3.20(s, 3H), 3.30 (s, 3H), 7.29- 7.31 (m, 1H), 7.42-7.44 (m, 1H), 7.48-7.50(m,1H), 7.64(s, 1H) Step-2: 1-(3-Bromophenyl)-3-oxocyclobutane-1-carbonitrile To a stirred solution of 1-(3-bromophenyl)-3,3-dimethoxycyclobutane-1-carbonitrile (0.96 g, 3.20 mmol), in 80 mL of acetone was added PTSA at room temperature for 48h. The reaction was quenched with water and extracted twice with ethyl acetate. The organic layer was washed with brine solution, dried over anhydrous Na 2 SO4 and concentrated and purified to give 400mg of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 3.9-3.75 (m, 2H), 4.06-4.11 (m, 2H), 7.36 (t, J=7.6 Hz, 1H), 7.45 (d, J= 8.0Hz, 1H), 7.56 (d, J= 8.0Hz, 1H), 7.66 (s, 1H). 1-(3-Bromophenyl)-3,3-difluorocyclobutane-1-carbonitrile To a stirred solution of 1-(3-bromophenyl)-3-oxocyclobutane-1-carbonitrile (0.95g, 3.8 mmol) in DCM (20 mL) was added DAST (2.45g, 15.2mmol) at 0 o C and stirred at room temperature for 18 h. The reaction was quenched with saturated NaHCO 3 and extracted with ethyl acetate. The organic layer was washed with water, brine solution and dried over anhydrous Na 2 SO4. The solvent was evaporated and purified to obtain 760mg of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 3.17-3.27 (m, 2H), 3.49-3.57 (m, 2H), 7.35 (t, J=7.6 Hz, 1H), 7.42 (d, J= 7.6 Hz, 1H), 7.55 (d, J= 7.6 Hz, 1H), 7.62 (s, 1H). Step-4: 1-(3-Bromophenyl)-3,3-difluorocyclobutane-1-carboxylic acid To a stirred solution of 1-(3-bromophenyl)-3,3-difluorocyclobutane-1-carbonitrile (2.0 g, 7.35 mmol) in acetic acid (4.0 ml) and water (4.0ml) was added conc H 2 SO 4 (4.0 mL) at 0°C. The reaction mixture was warmed to room temperature and heated to 120°C for 16 h. The mixture was cooled to room temperature and diluted with water. Precipitated solid was filtered dried well to yield 1.9 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 3.08-3.18 (m, 2H), 3.30-3.40 (m, 2H), 7.36 (t, J=4.4 Hz, 2H), 7.52 (d, J= 6.4 Hz, 1H), 7.54(s, 1H), 13.01-13.16 (brs, 1H). ESI-MS (m/z) 291 (M) + Step-5: 2-(1-(3-Bromophenyl)-3,3-difluorocyclobutane-1-carbonyl)-N-m ethylhydrazine-1- carbothioamide To a stirred solution of 1-(3-bromophenyl)-3,3-difluorocyclobutane-1-carboxylic acid (120 mg, 0.412 mmol) in DMF (3.0 mL) was added N-methylhydrazinecarbothioamide (48mg, 0.453 mmol). To this reaction mixture EDCI.HCl (118mg, 0.618mmol), triethylamine (54mg, 0.536mmol) and HOBt (72mg, 0.536mmol) was added. The reaction mixture was stirred at room temperature for 18h. The mixture was quenched by adding water, aq. Layer was extracted with ethyl acetate. Organic layer was separated, concentrated to yield 140mg desired product. ESI-MS (m/z) 378.0 (M+H) + Step-6: 5-(1-(3-Bromophenyl)-3,3-difluorocyclobutyl)-4-methyl-2,4-di hydro-3H-1,2,4- triazole-3-thione To a stirred solution of 2-(1-(3-bromophenyl)-3,3-difluorocyclobutane-1-carbonyl)-N- methylhydrazine-1-carbothioamide (2.9 g, 7.67 mmol) in 1N NaOH (100 mL) was stirred at room temperature for 16 h. The reaction mixture was acidified using 2N HCl and stirred for 15 min. The precipitated solid was filtered, washed with excess water and dried under vacuum to yield 2.1 g of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 3.04 (s, 3H), 3.38-3.47 (m, 2H), 3.58-3.68 (m, 2H), 7.33-7.40 (m, 2H), 7.55-7.59 (m, 2H), 13.86 (brs, 1H); ESI-MS (m/z) 360 (M+H) + Step-7: 3-(1-(3-Bromophenyl)-3,3-difluorocyclobutyl)-4-methyl-4H-1,2 ,4-triazole To a stirred solution of 5-(1-(3-bromophenyl)-3,3-difluorocyclobutyl)-4-methyl-2,4-di hydro- 3H-1,2,4-triazole-3-thione (65mg, 0.18 mmol) in DCM (1.0 mL) and AcOH (0.144ml) was added 30% H 2 O 2 (0.045ml) solution at 0°C. The mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with water and extracted twice with DCM. The solvent was evaporated under reduced pressure and the solid obtained was purified by silica gel column chromatography to yield 43 mg of the desired product. 1 HNMR (400 MHz, CDCl 3 ): δ 3.27 (s, 3H), 3.29-3.36(m, 2H), 3.68-3.78(m, 2H), 7.20(d, J= 7.6Hz, 1H), 7.26(d, J= 8.0Hz, 1H), 7.43 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 8.09 (s, 1H); ESI MS (m/z) 328 (M+H) + 3-(3,3-Difluoro-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl )aniline In a sealed tube, to a stirred solution of 3-(1-(3-bromophenyl)-3,3-difluorocyclobutyl)-4- methyl-4H-1,2,4-triazole (300 mg, 0.914 mmol) in ACN (3.0 mL) was added aqueous NH 3 (3.0 mL), copper oxide (52 mg, 0.365 mmol) and stirred at 90°C for 16 h. The reaction mixture was extracted thrice with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and the solvent was evaporated under vacuum to give 280 mg of the desired product. 1 HNMR (400 MHz, DMSO-d6): δ 3.24 (s, 3H), 3.24-3.27 (m, 2H), 3.58-3.68 (m, 2H),5.16 (s, 2H), 6.37 (s, 1H), 6.56(d, J=7.6Hz,2H), 7.01 (t, J = 8.0 Hz, 1H), 8.40 (brs, 1H); ESI-MS (m/z) 265 (M+H) + Intermediate A21 3-(Cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)aniline Methyl 2-(3-bromophenyl)acetate To a stirred solution of 3-bromophenyl acetic acid (17 g) in methanol (300 mL) was dropwise added conc. H 2 SO 4 (10 mL) and heated to 110 o C for 18 h. The reaction mixture was concentrated under reduced pressure. The residue obtained was diluted with water and extracted thrice with ethyl acetate. The organic layer was washed with sat, NaHCO 3 solution and separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue obtained was purified with chromatography to get 9.3 g of the desired product as pale yellow oil. 1 HNMR (400 MHz, CDCl3) δ 3.62 (s, 2H), 3.72 (s, 3H), 7.19-7.28 (m, 2H), 7.41- 7.44 (m, 1H), 7.43 (s, 1H); ESI-MS (m/z) 229.07 (M+H) + Methyl 2-(3-bromophenyl)-2-cyclobutylacetate To a stirred solution of methyl 2-(3-bromophenyl)acetate (2 g, 8.77 mmol) in DMF (15 mL) was dropwise added potassium tert-butoxide solution (11.34 ml, 11.34 mmol) at 0°C. A solution of bromocyclobutane (1.41 g, 10.48 mmol) in DMF (5 ml) was dropwise added and stirred at room temperature for 18 h. The reaction mixture was quenched with sat NH 4 Cl solution and extracted twice with ethyl acetate. Then organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue obtained was purified with chromatography to get 1.21 g of the desired product as pale yellow oil. 1 HNMR (400 MHz, CDCl 3 ) δ 1.611-1.63(m, 1H), 1.82-1.88(m, 4 H), 2.18-2.21( m, 1H), 2.93-2.95( m, 1H), 3.52(d, J=11.2 Hz, 1H), 3.95 (s, 3H), 7.17(m, 2H), 7.38-7.41(m, 1H), 7.45 (s,1H); ESI-MS (m/z) 283.03 (M+H) + 2-(3-Bromophenyl)-2-cyclobutylacetohydrazide To a stirred solution of methyl 2-(3-bromophenyl)-2-cyclobutylacetate (1.1 g) in ethanol (10 mL) was added hydrazine hydrate (3 mL) and heated to 90°C for 18 h. The reaction mixture was evaporated completely and diluted with water. The mixture was extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to yield 1.05 g of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.48- 1.50 (m, 1H), 1.72-1.79 (m, 4H), 1.98-2.00 ( m, 1H), 2.92-2.94 ( m, 1H), 3.18 (d, J=9.6 Hz, 1H),4.22( brs, 2H), 7.23-7.29 (m, 2H),7.39-7.42 (m, 1H), 7.50(s,1H), 9.22(s, 1H); ESI-MS (m/z) 283.1 (M+H) + Step-4: 2-(2-(3-Bromophenyl)-2-cyclobutylacetyl)-N-methylhydrazine-1 -carbothioamide To a stirred solution of 2-(3-Bromophenyl)-2-cyclobutylacetohydrazide (1.0 g, 3.53 mmol) in THF (10 mL) was added dropwise methyl isothiocyanate (776 mg, 10.65 mmol) and heated to 90°C for 4 h. The mixture was concentrated under reduced pressure and the residue obtained was triturated with pentane. The solid obtained was filtered and dried under vacuum to yield 1.1 g of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.53-1.57(m, 1H), 1.76-1.80 (m, 3H), 1.91-1.98( m, 2H), 2.78-2.81(m, 1H), 2.85 ( s, 3H), 3.47( d, J=9.6 Hz, 1H),7.25-7.32 (m, 2H), 7.43( d, J=7.6 Hz, 1H), 7.52(s,1H), 7.60(bs,1H), 9.26(s, 1H), 9.90(s, 1H), ESI-MS (m/z) 356.1 (M+H) + Step-5: 5-((3-Bromophenyl)(cyclobutyl)methyl)-4-methyl-2,4-dihydro-3 H-1,2,4-triazole-3- thione To a stirred solution of 2-(2-(3-Bromophenyl)-2-cyclobutylacetyl)-N-methylhydrazine-1 - carbothioamide (1.1 g) in 1N NaOH (40 mL) was stirred at room temperature for 16 h. The reaction mixture was acidified using 2N HCL and stirred for 15 min. The precipitated solid was filtered, washed with excess water and dried under vacuum to yield 1.05 g of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.68-75 (m, 5H), 2.07-2.09 ( m, 1H), 2.94-2.96 (m, 1H), 3.20 (s, 3H), 4.25 (d, J=10.8 Hz, 1H), 7.23 (d, J=7.6 Hz, 1H), 7.31 (t, J=8 Hz, 1H), 7.45- 7.49 (m, 2H), 13.71 (s, 1H); ESI-MS (m/z) 338.0 (M+H) + Step-6: 3-((3-Bromophenyl)(cyclobutyl)methyl)-4-methyl-4H-1,2,4-tria zole To a stirred solution of 25-((3-bromophenyl)(cyclobutyl)methyl)-4-methyl-2,4-dihydro- 3H- 1,2,4-triazole-3-thione (1.6 g, 4.74 mmol) in DCM (30 ml) was added acetic acid (3.8 ml, 66.26 mmol) at 0°C and stirred the reaction mixture for 10 min, to that reaction mixture, 30% solution of H 2 O 2 (1.2 ml, 11.84 mmol) was added and stirred at 0°C for 2 h. The reaction mixture was diluted with DCM and washed with water, and sat NaHCO 3 solution. Then organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. The obtained product was stirred in diethyl ether, filtered and dried to obtain 607 mg of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.63-78 (m, 5H), 2.03-2.05( m, 1H), 3.06-3.10 ( m, 1H), 3.39 (s, 3H), 4.22 (d, J=10.4 Hz, 1H),7.27-7.28 (m, 2H), 7.41-7.44 (m, 2H), 8.34 (s, 1H); ESI-MS (m/z) 306.0 (M+H) + Step-7: 3-(Cyclobutyl(4-methyl-4H-1,2,4-triazol-3-yl)methyl)aniline In a sealed tube, to a stirred solution of 3-((3-Bromophenyl)(cyclobutyl)methyl)-4-methyl-4H- 1,2,4-triazole (500 mg, 1.63 mmol) in NMP (5 mL) were added aq. NH 3 (5 mL), Copper (I) oxide (70 mg 0.49 mmol) and stirred at 100°C for 16 h. The reaction mixture was diluted with ethyl acetate and filtered. The organic layer was separated out and dried over anhydrous sodium sulphate and concentrated under reduced pressure up to dryness. The residue obtained was triturated with diethyl ether to give 373 mg of the desired product. 1 H NMR (400 MHz, DMSO- d 6 ) δ 1.61-65 (m, 1H), 1.75-1.77 ( m, 4 H), 2.07-2.15( m, 1H), 3.08-3.10 ( m, 1H), 3.35 ( s, 3H), 3.92( d, J=10.4 Hz, 1H), 5.01( bs,2H), 6.32-3.39(m , 3H), 6.91(t, J=8 Hz, 1H), 8.32 (s, 1H); ESI-MS (m/z) 243.3 (M+H) + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-4. Table-4: Structure, Name and analytical data of intermediate (A22) Intermediate A23 3-((1s,3s)-3-Methyl-1-(5-methyl-1-trityl-1H-imidazol-4-yl)cy clobutyl)aniline Step-1: (1s,3s)-1-(3-Bromophenyl)-N-methoxy-N,3-dimethylcyclobutane- 1-carboxamide To a stirred solution of (1s,3s)-1-(3-bromophenyl)-3-methylcyclobutane-1-carboxylic acid (4.0 g, 14.86 mmol) in DCM (40 ml) was added CDI (4.81 g, 29.72 mmol) portion wise followed by AIBN (2.0 g, 12.33 mmol). The reaction mixture was stirred at room temperature for 1h. The N,O-Dimethylhydroxylamine / was added and stirred at room temperature for 16 h. The reaction mixture was quenched with water (50 ml) and extracted with DCM (3 x 100 ml). The organic layer dried over anhydrous Na 2 SO 4 and evaporated under reduced pressure to obtain product. The obtained product was purified by combiflash chromatography to afford 3.1 g of the title compound. 1 HNMR (DMSO-d 6 , 400 MHz) δ 1.09 (d, J = 5.2 Hz, 3H), 2.36-2.34 (m, 3H), 2.54-2.52 (m, 2H), 3.11 (s, 6H), 7.23 (t, J = 7.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.58 (s, 1H). Step-2: 1-((1s,3s)-1-(3-Bromophenyl)-3-methylcyclobutyl)propan-1-one To a stirred solution of (1s,3s)-1-(3-bromophenyl)-N-methoxy-N,3-dimethyl cyclobutane-1- carboxamide (3.0 g, 9.61 mmol) in dry THF (30 ml) at 0°C was added ethyl magnesium bromide (6.4 g, 48.05 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with NH 4 Cl solution (50 ml) and extracted with DCM (3 x 100 ml). The organic layer dried over anhydrous Na2SO4, evaporated under reduced pressure to obtain product. The obtained product was purified by combiflash chromatography to afford 2.0 gm of the title compound. 1 HNMR ( DMSO-d 6 , 400 MHz) δ 1.09 (d, J = 5.2 Hz, 3H), 2.24-2.19 (q, J = 7.2 Hz, 2H), 2.21 (t, J = 7.2 Hz, 3H), 2.40-2.36 (m, 3H), 2.58-2.54 (m, 2H), 7.27-7.23 (m, 2H), 7.50-7.39 (m, 1H), 7.51 (s, 1H); ESI-MS (m/z) 280 [M-H] + . Step-3: 1-((1s,3s)-1-(3-Bromophenyl)-3-methylcyclobutyl)-2-hydroxypr opan-1-one To a stirred solution of 1-((1s,3s)-1-(3-bromophenyl)-3-methylcyclobutyl)propan-1-one (2.0 g, 7.09 mmol) in dry THF (30 ml) at -78°C was added NaHMDS (1.95 g, 10.64 mmol, 1.0 M in THF). After 15 min, a solution of (R)-3-methyl-3-phenyl-2-(phenylsulfonyl)-1,2-oxaziridine (2.78 g, 10.64 mmol) was added at -78°C and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was quenched with NH 4 Cl solution (50 ml) and extracted with EtOAc (3 x 100 ml). The organic layer dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to obtain product. The obtained product was purified by combiflash chromatography to afford 1.4 g of the title compound. 1 HNMR (DMSO-d 6 , 400 MHz) δ 1.05- 1.09 (m, 6H), 2.29-2.24 (m, 1H), 2.45-2.30 (m, 1H), 2.52-2.49 (m, 2H), 2.69-2.64 (m, 2H), 4.22 (q, J = 6.8 Hz, 1H), 7.26-7.28 (m, 2H), 7.45-7.42 (m, 1H), 7.52 (s, 1H). 1-((1s,3s)-1-(3-Bromophenyl)-3-methylcyclobutyl)propane-1,2- dione To a stirred solution of 1-((1s,3s)-1-(3-bromophenyl)-3-methylcyclobutyl)-2-hydroxypr opan- 1-one (1.4 g, 4.71 mmol) in dry DCM (30 ml) at 0 °C was added DMP (3.99 g, 9.42mmol) portion wise. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with sat. NaHCO 3 solution and extracted thrice with DCM. The organic layer dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to obtain product. The obtained product was purified by combiflash chromatography to afford 1.1 g of the title compound. 1 HNMR (DMSO-d 6 , 400 MHz) δ 1.07 (d, J = 6 Hz, 3H), 2.18 (s, 3H), 2.39-2.42 (m, 3H), 2.70-2.71 (m, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 7.6 Hz, 1H), 7.52 (s, 1H). Step-5: 4-((1s,3s)-1-(3-Bromophenyl)-3-methylcyclobutyl)-5-methyl-1H -imidazole To a stirred solution of 1-((1s,3s)-1-(3-bromophenyl)-3-methylcyclobutyl)propane-1,2- dione (1.1 g, 3.72 mmol) in MeOH was added paraformaldehyde (0.12 g, 4.09 mmol) followed by ammonium acetate (2.87 g, 37.26 mmol). The reaction mixture was heated at 80 °C in a sealed tube for 16 h. The reaction mixture was concentrated and the product obtained was purified by combiflash chromatography to afford 1.0 g of the title compound. 1 HNMR (DMSO-d 6 , 400 MHz) δ 7.56 (s, 1H), 7.30-7.36 (m, 2H), 7.28 (s, 1H), 7.17 (t, J = 8.0 Hz, 1H), 5.01 (brs, 1H), 2.81-2.83 (m, 2H), 2.38-2.44 (m, 3H), 2.04 (s, 3H), 1.11 (d, J = 5.6 Hz, 3H); ESI-MS (m/z) 305.1 [M+H] + 4-((1s,3s)-1-(3-Bromophenyl)-3-methylcyclobutyl)-5-methyl-1- trityl-1H-imidazole To a stirred solution of 4-((1s,3s)-1-(3-bromophenyl)-3-methylcyclobutyl)-5-methyl-1H - imidazole (1.0 g, 3.27 mmol) in dry DCM (30 ml) at 0°C was added triethylamine (0.31 g, 3.06 mmol) followed by trityl chloride (0.4 g, 1.46 mmol) portion wise. The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated and the obtained product was purified by combiflash chromatography to afford 1.3 g of the title compound. ESI- MS (m/z) 547.3 [M+H] + N-(3-((1s,3s)-3-methyl-1-(5-methyl-1-trityl-1H-imidazol-4-yl )cyclobutyl)phenyl)- 1,1-diphenylmethanimine To a stirred solution of 4-((1s,3s)-1-(3-bromophenyl)-3-methylcyclobutyl)-5-methyl-1- trityl- 1H-imidazole (1.2 g, 2.19 mmol) in dry dioxane (30 ml) was added benzophenoneimine (1.58 g, 8.76 mmol), Xantphos (0.25 g, 0.438 mmol) and cesium carbonate (1.78 g, 5.47 mmol). The reaction mixture was degassed for 15 min using nitrogen gas. Palladium acetate (0.049 g, 0.21mmol) was added and reaction mixture was heated at 80 °C in a sealed tube for 16h. The reaction mixture was diluted with EtOAc and filtered. The filtrate was concentrated and the crude compound was purified by combiflash chromatography to afford 1.1 g of the title compound. ESI-MS (m/z) 648.4 [M+H] + Step-8: 3-((1s,3s)-3-Methyl-1-(5-methyl-1-trityl-1H-imidazol-4-yl)cy clobutyl)aniline To a stirred solution of N-(3-((1s,3s)-3-methyl-1-(5-methyl-1-trityl-1H-imidazol-4- yl)cyclobutyl)phenyl)-1,1-diphenylmethanimine (1.1 g, 1.69 mmol) in MeOH (30 ml) was added hydroxylamine hydrochloride (0.35 g, 5.09 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated and the crude compound was partitioned between EtOAc (3 x 100 ml) and sat. NaHCO 3 (50 ml). The EtOAc layer was separated, dried over anhydrous Na 2 SO 4 and evaporated under reduced pressure to obtain product. The obtained product was purified by combiflash chromatography to afford 0.6 g of the title compound. ESI-MS (m/z) 484.3 [M+H] + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-5. Table-5: Structure, Name and analytical data of intermediate (A24) Intermediate A25 3-(3-Methyl-1-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2, 3-triazol-4- yl)cyclobutyl)aniline Step-1: 1-(3-Bromophenyl)-3-methylcyclobutane-1-carbaldehyde To a stirred solution of 1-(3-bromophenyl)-3-methylcyclobutane-1-carbonitrile (5.0 g, 0.02 mol) in DCM (50 ml) was added DIBAL (47 ml, 0.04 mol) at -78°C. The reaction mixture was stirred at -78 o C for 4 h. The reaction mixture was quenched with saturated solution of ammonium chloride, filtered and washed with ethyl acetate. The filtrate obtained was evaporated under reduced pressure to give 3.8 g of desired product. ESI-MS (m/z) 254 (M+2H) + Step-2: 4-(1-(3-Bromophenyl)-3-methylcyclobutyl)-5-methyl-1H-1,2,3-t riazole To a stirred solution of 1-(3-bromophenyl)-3-methylcyclobutane-1-carbaldehyde (3.8 g, 0.0150 mol) in dry DMSO (10 mL) was added nitroethane (1.61 ml, 0.0225 mol), sodium azide (1.17 g, 0.018 mol) and stirred at room temperature for 5 min, and then aluminium chloride (0.2 g, 0.0015 mol) was added. The reaction mixture was stirred for 10 min and heated at 70°C for 18 h. The reaction mixture was cooled to room temperature, quenched with ice water and extracted thrice with DCM. The organic layer was dried over anhydrous Na2SO4, evaporated under reduced pressure to obtain desired product which was purified by flash chromatography to give 2.3 g of desired product. ESI-MS (m/z) 306 [M+H] + Step-3: 4-(1-(3-Bromophenyl)-3-methylcyclobutyl)-5-methyl-1-(tetrahy dro-2H-pyran-2-yl)- 1H-1,2,3-triazole To a stirred solution of 5-(1-(3-bromophenyl)-3-methylcyclobutyl)-4-methyl-1H-1,2,3-t riazole (2.3 g, 7.516 mmol) in THF (30 ml) were added 2,3 dihydropyran (1.36 ml, 15.03 mmol) and trifluoroacetic acid (0.172 ml, 2.25 mmol). The reaction was stirred at room temperature for overnight. The reaction mass was quenched with sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was dried over sodium sulphate, evapoprated under reduced pressure. The obtained product was purified with flash chromatography to obtain 2.5 g of desired product as yellow oil. ESI-MS (m/z) 390 [M+H] + Step-5: 3-(3-Methyl-1-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-1,2, 3-triazol-4- yl)cyclobutyl)aniline To a stirred solution of 4-(1-(3-bromophenyl)-3-methylcyclobutyl)-5-methyl-1-(tetrahy dro- 2H-pyran-2-yl)-1H-1,2,3-triazole (2.0 g, 5.12 mmol) in acetonitrile (15 mL) was added aq. ammonia (15 mL), copper oxide (1.46 g, 10.24 mmol) and stirred at 110°C for overnight in a sealed tube. The reaction mixture was cooled to room temperature and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and evaporated under reduced pressure to obtain 0.8 g of desired product as yellow oil. ESI-MS (m/z) 327 [M+1] + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-6. Table-6: Structure, Name and analytical data of intermediate (A26) The mentioned below intermediates were synthesized by following the procedure described above for intermediate A11 and the analytical data are given in below Table-7. Table-7: Structure, Name and analytical data of intermediate (A27-A30) Intermediate B1 Methyl 5-bromo-1-(cyclopropylmethyl)-2-oxo-1,2-dihydropyridine-3-ca rboxylate Step-1: Methyl 5-bromo-2-oxo-1,2-dihydropyridine-3-carboxylate To a stirred solution of 5-Bromo-2-hydroxy nicotinic acid (5.0 g, 35.94 mmol) in dry methanol (100 mL) was added conc. H 2 SO 4 (1 mL) and refluxed for 18 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The obtained residue was basified with saturated sodium bicarbonate solution and stirred for 30 min. The solid obtained was filtered and dried under vacuum to give 4.2 g of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 3.75 (s, 3H), 7.99 (d, J = 2.8 Hz), 8.08 (d, J = 2.8 Hz, 1H), 12.41 (brs, 1H); ESI- MS (m/z) 233 (M+2H) + . Step-2: Methyl 5-bromo-1-(cyclopropylmethyl)-2-oxo-1,2-dihydropyridine-3-ca rboxylate To a stirred solution of methyl 5-bromo-2-oxo-1,2-dihydropyridine-3-carboxylate (250 mg, 1.077 mmol) in DMF (5 mL) was added potassium carbonate (223 mg, 1.616 mmol) and stirred at room temperature for 30 min. To this mixture was added cyclopropyl methyl bromide (157 μL, 1.616 mmol) and heated to 70°C for overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained residue was purified by silica gel chromatography to yield 126 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 0.35- 0.45 (m, 2H), 0.45- 0.55 (m, 2H), 1.18- 1.35 (m, 1H), 3.75 (s, 3H), 3.77 (d, J = 9.6 Hz, 2H), 8.058 (d, J = 2.8 Hz, 1H), 8.38 (d, J = 2.8 Hz, 1H); ESI-MS (m/z) 287 (M+2H) + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-8. Table-8: Structure, Name and analytical data of intermediates (B2-B4) Intermediate B5 Methyl 5-bromo-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3 -carboxylate To a stirred solution of methyl 5-bromo-2-oxo-1,2-dihydropyridine-3-carboxylate (5.2 gm, 22.413 mmol) in DMF (80 mL) was added cesium carbonate (10.9 g, 33.620 mmol) and stirred for 30 min at room temperature. To this mixture was added 2,2,2-Trifluoro ethyltrifluoromethane sulfate (7.8 g, 33.62 mmol) and heated to 70 °C for overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was over anhydrous sodium sulphate and concentrated. The obtained residue was purified by silica gel chromatography to yield 2.9 g of the desired compound. 1 HNMR (400 MHz, DMSO-d 6 ) δ 3.77 (s, 3H), 4.875 (q, J= 9.2 Hz, 2H), 8.14 (d, J = 2.4 Hz, 1H), 8.36 (d, J = 2.4 Hz, 1H); ESI- MS (m/z) 315 (M+2H) + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-9. Table-9: Structure, Name and analytical data of intermediate (B6) Intermediate B7 Methyl 5-bromo-1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylat e O Br O N O Step-1: Methyl 1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylate To a stirred solution of methyl 2-oxo-1,2-dihydropyridine-3-carboxylate (4.8 g, 31.16 mmol) in ethylene dichloride (150 mL) were added cyclopropyl boronic acid (5.30 g, 62.33 mmol), Cs 2 CO 3 (5.06 g, 15.58 mmol), pyridine (12.32 g, 155.8 mmol) and stirred under oxygen atmosphere for 30 min at room temperature. To this mixture was added Cu(OAc) 2 (5.65 g, 31.16 mmol) and stirred for 4 days. The reaction mixture was diluted with DCM and filtered. The filtrate obtained was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to yield 230 mg of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 0.83-0.87 (m, 2H), 0.99-1.04 (m, 2H), 3.32-3.38 (m, 1H), 3.73 (s, 3H), 6.26 (t, J = 7.2 Hz, 1H), 7.87 (d, J = 6.8 Hz, 1H), 8.0 (d, J = 7.2 Hz, 1H) ESI-MS (m/z) 194.1 (M+H) + Step-2: Methyl 5-bromo-1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylat e To a stirred solution of methyl 1-cyclopropyl-2-oxo-1,2-dihydropyridine-3-carboxylate (230 mg, 1.18 mmol) in DCM (10 mL) was added NBS (274 mg, 1.54 mmol) and the mixture was heated at 60°C for 18 h. The mixture was diluted with DCM and washed thrice with water. The organic layer was separated, dried over anhydrous sodium sulphate and concentrated under reduced pressure to yield 260 mg of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ1.12- 1.15 (m, 4H), 3.30-3.35 (m, 1H), 3.37 (s, 3H), 6.02 (s, 1H), 8.09 (s,1H); ESI-MS (m/z) 274.2 (M+ 2H) + Intermediate B8 2-Oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 -carboxylic acid Step-1: Methyl 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 -carboxylate To a stirred solution of 5-bromo-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3 - carboxylate (Intermediate B5) (1.5 g, 4.76 mmol) and potassium vinyl trifluoroborate (1.91 gm., 14.28 mmol) in a solvent mixture of toluene (50 mL)/water (15 mL) was degassed for 15 min. To this reaction mixture were added K 3 PO 4 (4 g, 19.04 mmol), Pd(dppf)Cl 2. DCM (390 mg, 0.476 mmol) and heated to 100°C for 5 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under vacuum. The obtained residue was purified by silica gel column chromatography to yield 1.09 g of the desired compound. 1 H NMR (400 MHz, DMSO- d 6 ) δ 3.78 (s, 3H), 4.90 (q, J = 9.2 Hz, 2H), 5.22 (d, J= 11.2 Hz, 1H), 5.68 (d, J = 17.6 Hz, 1H), 6.45- 6.6 (m, 1H), 8.103 (d, J = 2Hz, 1H), 8.33 (d, J = 2.8 Hz, 1H); ESI-MS (m/z) 262.3 (M+H) + 2-Oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 -carboxylic acid To a stirred solution of methyl 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 - carboxylate (1 g, 3.831 mmol) in THF/MeOH (40 mL, 1:1) was added aqueous LiOH (481 mg, 11.49 mmol) and stirred at room temperature for overnight. The reaction mixture was concentrated and the residue obtained was diluted with water and acidified using 1N HCl. The solid precipitated was filtered and dried to yield 809 mg desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 5.01 (q, J = 9.2 Hz, 2H), 5.28 (d, J = 11.2 Hz, 1H), 5.76 (d, J = 17.6 Hz, 1H), 6.50- 6.70 (m, 1H), 8.19 (s, 1H), 8.53 (d, J = 2.4 Hz, 1H), 13.86 (brs, 1H); ESI-MS (m/z) 248.2 (M+H) + The analytical data of the intermediate prepared by following the procedure described above are given in below Table-10. Table-10: Structure, Name and analytical data of intermediates (B9-B12) Intermediate B13 1-(Difluoromethyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3-carbo xylic acid Step-1: Methyl 5-bromo-1-(difluoromethyl)-2-oxo-1,2-dihydropyridine-3-carbo xylate O O Br O N F F To a stirred solution of methyl 5-bromo-2-oxo-1,2-dihydropyridine-3-carboxylate (300 mg, 1.293 mmol) in DMF (2 mL) were added K 2 CO 3 (356 mg, 2.586 mmol), sodium 2-chloro-2,2- difluoroacetate (393 mg, 2.586 mmol) at room temperature and heated to 80 o C for 18 h. The reaction mixture was quenched with water and extracted thrice with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated. The residue obtained was purified by silica gel chromatography to yield 201 mg of the desired product. 1 H NMR (400 MHz, DMSO) δ 3.78 (s, 3H), 7.79 (t, J = 59.2 Hz, 1H), 8.18 (s, 1H), 8.42 (s, 1H); ESI-MS (m/z) 283.6 (M+H) + Step-2: Methyl 1-(difluoromethyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3-carbo xylate To a stirred solution of methyl 5-bromo-1-(difluoromethyl)-2-oxo-1,2-dihydropyridine-3- carboxylate (150 mg, 0.5319 mmol) and potassium vinyl trifluoroborate (212 mg, 1.595 mmol) in a solvent mixture of toluene (5 mL)/water (1mL) was degassed for 15 min. To this reaction mixture were added K 3 PO 4 (451 mg, 2.127 mmol), Pd(dppf)Cl 2. DCM (43 mg,0.05319 mmol) and heated to 120°C for 2 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layers were separated, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue obtained was purified by silica gel column chromatography to yield 120 mg of the desired product. 1 H NMR (400 MHz, DMSO) δ 3.80 (s, 3H), 5.27 (d, J = 11.2 Hz, 1H), 5.76 (m, 1H), 6.65 (m, 1H), 7.87 (t, J = 59.2 Hz, 1H), 8.18 (s, 1H), 8.41 (s, 1H); ESI-MS (m/z) 230.1 (M+H) + Step-3: 1-(Difluoromethyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3-carbo xylic acid To a stirred solution of methyl 1-(difluoromethyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3- carboxylate (27 mg, 0.0118 mmol) in THF/Methanol (2 mL) at 0 o C was added aqueous lithium hydroxide (14.85 mg, 0.3537 mmol) and stirred at 0 o C for 30 min. The solvent was evaporated and acidified with 1N citric acid solution. The aqueous layer was extracted twice with 10% MeOH / DCM and dried over sodium sulphate. The organic layer was concentrated under reduced pressure to yield 19 mg of the desired product. ESI-MS (m/z) 216.20 (M+H) + Intermediate B14 2-Oxo-1-(prop-2-yn-1-yl)-5-vinyl-1,2-dihydropyridine-3-carbo xylic acid Methyl 5-bromo-2-oxo-1-(3-(trimethylsilyl)prop-2-yn-1-yl)-1,2-dihyd ropyridine-3- carboxylate To a stirred solution of methyl 5-bromo-2-hydroxynicotinate (2 g, 8.66 mmol) in dry DMF (20 mL) was added cesium carbonate (4.2 g, 12.99 mmol) and resulting mixture was stirred at room temperature for 30 min. The (3-bromoprop-1-yn-1-yl)trimethylsilane (1.65 mL, 10.39 mmol) was added and stirred at room temperature for 2h. The reaction mixture was diluted with water and extracted thrice with ethyl acetate and the combined organic layers were washed with water and concentrated. The obtained residue was purified by column chromatography to yield 1.8 g of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 0.24 (s, 9H), 3.92 (s, 3H), 4.78 (s, 2H), 8.13 (d, J = 2.8 Hz, 1H), 8.23 (d, J = 2.8 Hz, 1H); ESI-MS (m/z) 344.0 (M+2H) + Methyl 2-oxo-1-(prop-2-yn-1-yl)-5-vinyl-1,2-dihydropyridine-3-carbo xylate To a stirred solution of methyl 5-bromo-2-oxo-1-(3-(trimethylsilyl)prop-2-yn-1-yl)-1,2- dihydropyridine-3-carboxylate (1.8 g, 5.232 mmol) in toluene (25 mL) and water (5 mL) was added K 3 PO 4 (4.4 g, 20.93 mmol) and trifluoro(vinyl)-l4-borane, potassium salt (2.0 g, 15.69 mmol) under nitrogen atmosphere and the mixture was degassed for 10 min. The [1,1′- bis(diphenylphosphino)ferrocene] dichloropalladium(II) (426 mg, 0.523 mmol) was added and the mixture was stirred at 100°C for overnight under nitrogen atmosphere. The mixture was diluted with water and extracted thrice with ethyl acetate. The organic layer was separated and concentrated under vacuum, The obtained residue was purified by silica gel column chromatography to give 190 mg of the product as an off-white solid; 1 H NMR (400 MHz, CDCl 3 ) δ 3.94 (s, 3H), 4.81 (s, 2H), 5.24 (d, J = 10.8 Hz, 1H), 5.59 (d, J = 17.6 Hz, 1H), 6.43- 6.51 (m, 1H), 7.97 (d, J = 2.4 Hz, 1H), 8.39 (d, J = 2.8 Hz, 1H). 2-Oxo-1-(prop-2-yn-1-yl)-5-vinyl-1,2-dihydropyridine-3-carbo xylic acid To a stirred solution of methyl 2-oxo-1-(prop-2-yn-1-yl)-5-vinyl-1,2-dihydropyridine-3- carboxylate (500 mg, 2.304 mmol) in THF (15 mL), methanol (5 mL) and water (5 mL) was added lithium hydroxide monohydrate (193 mg, 4.608 mmol) and resulting mixture was stirred at room temperature for overnight. The solvent was evaporated completely under reduced pressure, acidified with HCl, solid obtained was collected by filtration to yield 170 mg of desired product as off white solid. 1 H NMR 400 MHz, DMSO-d 6 ) δ 5.30 (d, J = 11.2 Hz, 1H), 5.82 (d, J = 17.6 Hz, 1H), 5.93 (d, J = 6.4 Hz, 2H), 7.58 (d, J =6.4 Hz, 1H), 8.12 (d, J = 2.4 Hz, 1H).8.52-8.59 (m, 1H), 14.00 (s, 1H); ESI-MS (m/z) 204.1 (M+H) + Intermediate B15 1-(4-Fluorophenyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3-carbo xylic acid Methyl 5-bromo-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbo xylate To a stirred solution of methyl 5-bromo-2-oxo-1, 2-dihydropyridine-3-carboxylate (2.0 g, 1.077 mmol) in DCM (50 mL) were added (4-fluorophenyl)boronic acid (3.2 g, 23.27 mmol), pyridine (3.4 mL, 34.48 mmol) followed by diacetoxycopper (3.4 g, 17.24 mmol) and activated molecular sieves and stirred at room temperature for overnight. The reaction mixture was filtered and diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained residue was purified by silica gel chromatography to yield 650 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 3.76 (s, 3H), 7.34-7.39 (m, 2H), 7.50-7.54 (m, 2H), 8.15 (d, J = 3.0 Hz, 1H), 8.30 (d, J = 3.0 Hz, 1H); ESI-MS (m/z) 327.8 (M+H) + Methyl 1-(4-fluorophenyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3-carbo xylate To a stirred solution of methyl 5-bromo-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3- carboxylate (650 mg, 1.99 mmol) and potassium vinyl trifluoroborate (800 mg, 5.98 mmol) in a mixture of toluene (5 mL) and water (2 mL) was degassed for 15 min. To this reaction mixture were added K 3 PO 4 (1.7 g, 7.96 mmol), Pd(dppf)Cl 2. DCM (163 mg, 199 mmol) and heated to 100°C for 3 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layers were separated, dried over anhydrous sodium sulfate and concentrated under vacuum. The obtained residue was purified by silica gel column chromatography to yield 550 mg of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 3.78 (s, 3H), 5.17 (d, J = 11.3 Hz, 1H), 5.69 (d, J = 17.6 Hz, 1H), 6.56 (d, J = 17.7 Hz, 1H), 7.35- 7.40 (m, 2H), 7.50-7.54 (m, 2H), 8.07 (s, 1H), 8.35 (s, 1H); ESI-MS (m/z) 274.1 (M+H) + Step-3: 1-(4-Fluorophenyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3-carbo xylic acid To a stirred solution of methyl 1-(4-fluorophenyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3- carboxylate (550 mg, 2.01 mmol) in THF / Methanol / Water (25 mL) at 0 o C was added aqueous lithium hydroxide (423 mg, 10.07 mmol) and stirred at same temperature for overnight. The solvent was evaporated and acidified with 1 N hydrochloric acid solution. The aqueous layer was extracted twice with 10% MeOH/DCM and dried over sodium sulphate. The organic layer was concentrated under reduced pressure to yield 400 mg of the desired product. ESI-MS (m/z) 260.1 (M+H) + . The mentioned below intermediates were synthesized by following the procedure described above for intermediate B8 and the analytical data are given in below Table-11. Table-11: Structure, Name and analytical data of intermediates (B16-B19) EXAMPLES Method A: Example-1 1-(Cyclopropylmethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-tr iazol-3-yl)propan-2- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridin e-3-carboxamide Step-1: Methyl 5-bromo-2-oxo-1,2-dihydropyridine-3-carboxylate To a stirred solution of 5-bromo-2-hydroxy nicotinic acid (5.0 g, 35.94 mmol) in dry Methanol (100 mL) was added conc. H 2 SO 4 (1 mL) and refluxed for 18 h. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The obtained residue was basified with saturated sodium bicarbonate solution and stirred for 30 min. The solid obtained was filtered and dried under vacuum to give 4.2 g of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 3.75 (s, 3H), 7.99 (d, J = 2.8 Hz), 8.08 (d, J = 2.8 Hz, 1H), 12.41 (brs, 1H); ESI- MS (m/z) 233 (M+2H) + . Step-2: Methyl 5-bromo-1-(cyclopropylmethyl)-2-oxo-1,2-dihydropyridine-3-ca rboxylate To a stirred solution of methyl 5-bromo-2-oxo-1,2-dihydropyridine-3-carboxylate (250 mg, 1.077 mmol) in DMF (5 mL) was added potassium carbonate (223 mg, 1.616 mmol) and stirred at room temperature for 30 min. To this mixture was added cyclopropyl methyl bromide (157 μL, 1.616 mmol) and heated to 70°C for overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained residue was purified by silica gel chromatography to yield 126 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 0.35- 0.45 (m, 2H), 0.45- 0.55 (m, 2H), 1.18- 1.35 (m, 1H), 3.75 (s, 3H), 3.77 (d, J = 9.6 Hz, 2H), 8.058 (d, J = 2.8 Hz, 1H), 8.38 (d, J = 2.8 Hz, 1H); ESI-MS (m/z) 287 (M+2H) + Step-3: Methyl 1-(cyclopropylmethyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3-ca rboxylate To a stirred solution of methyl 5-bromo-1-(cyclopropylmethyl)-2-oxo-1,2-dihydropyridine-3- carboxylate (500 mg, 1.74 mmol) and potassium vinyl trifluoroborate (700 mg, 5.2 mmol) in a solvent mixture of toluene and water (30 mL) and degassed for 15 min. To this reaction mixture were added K 3 PO 4 (1.5 gm, 6.9 mmol), Pd(dppf)Cl 2. DCM (140 mg, 0.17 mmol) and heated to 100°C for 5 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated and dried over anhydrous sodium sulfate and concentrated under vacuum. The obtained residue was purified by silica gel column chromatography to yield 350 mg of the desired compound. 1 HNMR (400 MHz, DMSO-d 6 ) δ 0.30 - 0.45 (m, 2H), 0.45- 0.55 (m, 2H), 1.15- 1.35 (m, 1H), 3.77 (s, 3H), 3.78 (d, J = 8.8 Hz, 2H), 5.14 (d, J = 11.2 Hz, 1H), 5.64 (d, J = 17.6 Hz, 1H), 6.48 - 6.57 (m, 1H), 8.16 (d, J = 2.8 Hz, 1H), 8.23 (d, J = 2.8 Hz, 1H); ESI-MS (m/z) 234.2 (M+H) + Methyl 1-(cyclopropylmethyl)-5-formyl-2-oxo-1,2-dihydropyridine-3-c arboxylate To a stirred solution of methyl 1-(cyclopropylmethyl)-2-oxo-5-vinyl-1,2-dihydropyridine-3- carboxylate (375 mg, 1.712 mmol) in THF / H 2 O (4:1, 25 mL) were added NaIO 4 (768 mg, 3.59 mmol) followed by 2.5% OsO 4 in t-BuOH (36 μl, 0034 mmol). The reaction mixture was stirred at RT for overnight. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to yield 303 mg of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 0.41- 0.55 (m, 4H), 1.26- 1.31 (m, 1H), 3.79 (s, 3H), 3.88 (d, J = 7.6 Hz, 2H), 8.355 (d, J = 2.8 Hz, 1H), 8.9 (d, J = 2.8 Hz, 1H), 9.66 (s, 1H); ESI-MS (m/z) 236 (M+H) + Step-5: Methyl 1-(cyclopropylmethyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dih ydro pyridine-3- carboxylate To a stirred solution of methyl 1-(cyclopropylmethyl)-5-formyl-2-oxo-1,2-dihydropyridine-3- carboxylate (180 mg, 0.765 mmol) and piperidine (152 μl, 1.53 mmol) in DCM (5 mL) was added catalytic amount of acetic acid and stirred for 2 h. To this reaction mixture was added sodium cyano borohydride (144 mg, 2.295 mmol) and stirred at room temperature for overnight. The reaction mixture was quenched with Methanol and concentrated. The obtained residue was purified by flash chromatography to yield 172 mg of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 0.40- 0.60 (m, 4H), 1.30- 1.40 (m, 1H), 1.50- 1.60 (m, 2H), 1.60 - 1.75 (m, 4H), 2.90-3.10 (m, 4H), 3.77 (s, 3H), 3.78 (d, J = 9.2 Hz, 2H), 4.12 (brs, 2H), 8.10- 8.30 (m, 2H); ESI-MS (m/z) 305.3 (M+H) + 1-(Cyclopropylmethyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dih ydropyridine-3- carboxylic acid To a stirred solution of methyl 1-(cyclopropylmethyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2- dihydropyridine-3-carboxylate (100 mg, 0.328 mmol) in THF / MeOH (2 mL) was added aqueous LiOH (69 mg, 1.644 mmol) and stirred at room temperature for overnight. The reaction mixture was concentrated and the residue obtained was diluted with water and acidified with 1N citric acid. The aqueous layer was extracted with 20 % MeOH / DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to yield 74 mg of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 0.43- 0.55 (m, 4H), 1.20- 1.30 (m, 1H), 1.30- 1.40 (m, 2H), 1.40- 1.60 (m, 4H), 2.30- 2.50 (m, 4H), 3.35 (s, 2H), 3.96 (d, J = 7.2 Hz, 2H), 8.23 (s, 1H), 8.37 (s, 1H), 14.8 (brs, 1H); ESI-MS (m/z) 291.4 (M+H) + 1-(Cyclopropylmethyl)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-tr iazol-3-yl)propan-2- yl)phenyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2-dihydropyridin e-3-carboxamide To a stirred solution of 1-(cyclopropylmethyl)-2-oxo-5-(piperidin-1-ylmethyl)-1,2- dihydropyridine-3-carboxylic acid (70 mg, 0.241 mmol) in DMF was added HATU (110 mg, 0.289 mmol) and stirred at RT for 30 min. To this mixture were added DIPEA (129 μl, 0.723 mmol) and 3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)an iline (66 mg, 0.289 mmol) and stirred for overnight. The reaction mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated. The residue obtained was purified by flash column chromatography to yield 9 mg of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 0.40- 0.60 (m, 4H), 1.20- 1.30 (m, 2H), 1.30- 1.40 (m, 1H), 1.43 (s, 6H), 1.60 - 1.80 (m, 4H), 2.30- 2.40 (m, 4H), 2.94 (s, 2H), 3.12 (s, 3H), 3.31 (s, 2H), 3.95 (d, J = 7.2 Hz, 2H), 7.03 (d, J = 8 Hz, 1H), 7.26 (t, J = 8 Hz, 1H), 7.55 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 8.07 (s, 1H), 8.21 (s, 1H), 8.42 (d, J = 2.4 Hz, 1H), 12.2 (brs, 1H); ESI-MS (m/z) 503.4 (M+H) + Method B: Example-2 N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl )phenyl)-2-oxo-5-(piperidin-1- ylmethyl)-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-car boxamide Step-1: 5-Bromo-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3 -carboxylic acid To a stirred solution of methyl 5-bromo-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3 - carboxylate (1 g, 3.174 mmol) in THF / MeOH (20, mL) was added aqueous LiOH (666 mg, 15.873 mmol) at room temperature for overnight. The reaction mixture was concentrated and the obtained residue diluted with water and acidified with 1N HCl. The solid obtained was filtered and dried under vacuum to yield 630 mg of the desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 4.97 (q, J = 8.8 Hz, 2H), 8.3 (s, 1H), 8.47 (s, 1H), 13.53 (brs, 1H); ESI-MS (m/z) 301.9 (M+2H) + Step-2: 5-Bromo-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)pro pan-2-yl)phenyl)-2- oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxami de To a stirred solution of 5-bromo-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3 - carboxylic acid (250 mg, 0.833 mmol) in DMF (10 mL) was added HATU (380 mg, 0.999 mmol) and stirred at room temperature for 30 min. To this mixture were added DIPEA (430 μL, 2.499 mmol) and 3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)an iline (191 mg, 0.833 mmol) and stirred for overnight. The reaction mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained residue was purified by flash column chromatography to yield 330 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.42 (s, 6H), 2.98 (s, 2H), 3.16 (s, 3H), 5.04 (q, J = 9.2 Hz, 2H), 7.07 (d, J =8 Hz, 1H), 7.28 (t, J = 8 Hz, 1H), 7.55 (s, 1H), 7.62 (d, J =8 Hz, 1H), 8.23 (s, 1H), 8.45- 8.55 (m, 2H), 11.50 (s, 1H); ESI-MS (m/z) 512.2 (M+H) + Step-3: N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl )phenyl)-2-oxo-1- (2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3-carboxa mide To a stirred solution of 5-bromo-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)pro pan-2- yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridin e-3-carboxamide (250 mg, 0.488 mmol) and potassium vinyl trifluoroborate (196 mg, 1.464 mmol) in toluene (5 mL) / water (1 mL) was degassed for 10 min. To this reaction mixture were added K 3 PO 4 (414 mg, 1.954 mmol), Pd(dppf)Cl 2. DCM (40 mg, 0.0488 mmol) and heated to 100°C for 3 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under vacuum. The obtained residue was purified by silica gel column chromatography to yield 230 mg of the desired product. 1 HNMR (400 MHz, DMSO-d6) δ 1.42 (s, 6H), 2.98 (s.2H), 3.33 (s, 3H), 5.07 (q, J = 9.2 Hz, 2H), 5.31 (d, J = 10.8 Hz, 1H), 5.79 (d, J = 17.6 Hz, 1H), 6.60 - 6.75 (m, 1H), 7.0-7.15 (m, 1H), 7.15-7.25 (m, 1H), 7.25-7.40 (m, 1H), 7.6-7.75 (m, 1H), 8.15-8.30 (m, 2H), 8.73 (s, 1H), 11.64 (s, 1H); ESI-MS (m/z) 460.2 (M+H) + . Step-4: 5-Formyl-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)pr opan-2-yl)phenyl)-2- oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxami de To a stirred solution of N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydr opyridine-3-carboxamide (215 mg, 0.468 mmol) in THF / H 2 O (4:1, 25 mL) were added NaIO 4 (200 mg, 0.936 mmol) followed by 2.5% OsO 4 in t-BuOH (10 μL, 0.0009 mmol). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to yield 89 mg of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.43 (s, 6H), 2.99 (s, 2H), 3.13 (s, 3H), 5.10-5.25 (m, 2H), 7. 7.15 (m, 1H), 7.20-7.35 (m, 1H), 7.50- 7.75 (m, 2H), 8.21 (brs, 1H), 8.70-8.85 (m, 1H), 8.94 (s, 1H), 9.81 (s, 1H), 11.21 (s, 1H); ESI- MS (m/z) 461.9 (M+H) + Step-5: N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl )phenyl)-2-oxo-5- (piperidin-1-ylmethyl)-1-(2,2,2-trifluoroethyl)-1,2-dihydrop yridine-3-carboxamide To a stirred solution of 5-formyl-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)pr opan-2- yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridin e-3-carboxamide (70 mg, 0.151 mmol) and piperidine (45 μl, 0.555 mmol) in DCM (4 mL) was added drop of acetic acid and stirred for 2 h. To this reaction mixture was added sodium triacetoxy borohydride (96 mg, 0.455 mmol) and stirred at room temperature for overnight. The reaction mixture was quenched with aqueous bicarbonate solution and extracted twice with ethyl acetate. The organic layer was concentrated under reduced pressure and the obtained residue was purified by flash chromatography to yield 12 mg of the desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.25- 1.40 (m, 2H), 1.43 (s, 6H), 1.40-1.70 (m, 4H), 2.15-2.45 (m, 4H), 2.98 (s, 2H), 3.12 (s, 3H), 3.42 (brs, 2H), 5.0-5.20 (m, 2H), 7.05 (brs, 1H), 7.27 (brs, 1H), 7.5-7.7 (m, 2H), 8.02 (brs, 1H), 8.21 (s, 1H), 8.48 (brs, 1H), 11.75 (brs, 1H); ESI-MS (m/z) 531.2 (M+H) + The details of synthesis and analytical data of the examples synthesized from the above- mentioned methods are given below in Table-12. Table-12: Structure, method, intermediates used, chemical name and analytical data of Examples (3-8) Method C: Example-9 (S)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan- 2-yl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3- carboxamide Step-1: Methyl 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 -carboxylate To a stirred solution of 5-bromo-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3 - carboxylate (1.5 g, 4.76 mmol) and potassium vinyl trifluoroborate (1.91 gm., 14.28 mmol) in a solvent mixture of toluene (50 mL)/water (15 mL) was degassed for 15 min. To this reaction mixture were added K3PO4 (4 g, 19.04 mmol), Pd(dppf)Cl2.DCM (390 mg, 0.476 mmol) and heated to 100°C for 5 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated under vacuum. The obtained residue was purified by silica gel column chromatography to yield 1.09 g of the desired compound. 1 HNMR (400 MHz, DMSO-d 6 ) δ 3.78 (s, 3H), 4.90 (q, J = 9.2 Hz, 2H), 5.22 (d, J= 11.2 Hz, 1H), 5.68 (d, J = 17.6 Hz, 1H), 6.45- 6.6 (m, 1H), 8.103 (d, J = 2Hz, 1H), 8.33 (d, J = 2.8 Hz, 1H); ESI-MS (m/z) 262.3 (M+H) + Step-2: 2-Oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 -carboxylic acid To a stirred solution of methyl 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 - carboxylate (1 g, 3.831 mmol) in THF / MeOH (40 mL, 1:1) was added aqueous LiOH (481 mg, 11.49 mmol) and stirred at room temperature for overnight. The reaction mixture was concentrated and the residue obtained was diluted with water and acidified using 1N HCl. The solid precipitated was filtered and dried to yield 809 mg desired product. 1 HNMR (400 MHz, DMSO-d 6 ) δ 5.01 (q, J = 9.2 Hz, 2H), 5.28 (d, J = 11.2 Hz, 1H), 5.76 (d, J = 17.6 Hz, 1H), 6.50- 6.70 (m, 1H), 8.19 (s, 1H), 8.53 (d, J = 2.4 Hz, 1H), 13.86 (brs, 1H); ESI-MS (m/z) 248.2 (M+H) + Step-3: N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl )phenyl)-2-oxo-1- (2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3-carboxa mide To a stirred solution of 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 - carboxylic acid (800 mg, 3.238 mmol) in DMF (15 mL) was added HATU (1.5 g, 3.885 mmol) and stirred at room temperature for 30 min. To this mixture were added DIPEA (1.7 ml, 9.714 mmol) and 3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2-yl)an iline (744 mg, 3.238 mmol) and stirred for overnight. The reaction mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained residue was purified by flash column chromatography to yield 1.41 g of the desired compound. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.43 (s, 6H), 3.02 (s, 2H), 3.17 (s, 3H), 5.07 (q, J = 9.2 Hz, 2H), 5.32 (d, J = 10.8 Hz, 1H), 5.79 (d, J = 17.6 Hz, 1H), 6.55- 6.75 (m, 1H), 7.06 (d, J = 8Hz, 1H), 7.28 (d, J = 8 Hz, 1H), 7.55- 7.70 (m, 2H), 8.26 (d, J = 2 Hz, 1H), 8.33 (brs, 1H), 8.73 (d, J = 2.4 Hz, 1H), 11.65 (s, 1H); ESI-MS (m/z) 460.3 (M+H) + Step-4: 5-Formyl-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)pr opan-2-yl)phenyl)-2- oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxami de To a stirred solution of N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan-2- yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydr opyridine-3-carboxamide (1.5 g, 3.267 mmol) in THF / H 2 O (50 mL) were added NaIO 4 (2 g, 6.534 mmol) followed by 2.5% OsO 4 in t-BuOH (320 μl , 0.032 mmol). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to yield 1.12 g of the desired compound. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.47 (s, 6H), 2.99 (s, 2H), 3.13 (s, 3H), 5.19 (q, J = 9.2 Hz, 2H), 7.07 (d, J = 8 Hz, 1H), 7.23 (t, J = 8 Hz, 1H), 7.55 (s, 1H), 7.66 (d, J = 8 Hz, 1H), 8.22 (d, J = 3.2 Hz, 1H), 8.78 (d, J = 2.4 Hz, 1H), 8.95 (d, J = 2.4 Hz, 1H), 9.81 (s, 1H), 11.22 (s, 1H); ESI-MS (m/z) 462.1 (M+H) + Step-5: (S)-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)propan- 2-yl)phenyl)-5-((3- methylpiperidin-1-yl)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)- 1,2-dihydropyridine-3- carboxamide To a stirred solution of 5-formyl-N-(3-(2-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)pr opan-2- yl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridin e-3-carboxamide (80 mg, 0.173 mmol) and (3S)-3-Methylpiperidine HCl (47 mg, 0.347 mmol) in DCM (3 mL) was added DIPEA (89 μL, 0.519 mmol) and stirred for 2 h. To this reaction mixture was added sodium triacetoxyborohydride (110 mg, 0.519 mmol) and stirred at room temperature for overnight. The reaction mixture was quenched with aqueous bicarbonate solution and extracted twice with ethyl acetate. The organic layer was concentrated under reduced pressure and the obtained residue was purified by supercritical fluid chromatography (SFC) to yield 29 mg of the desired compound. 1 HNMR (400 MHz, DMSO-d 6 ) δ 0.82 (d, J = 5.2 Hz, 3H), 1.43 (s, 6H), 1.45-1.70 (m, 5 H), 1.80-1.92 (m, 1H), 2.45-2.50 (m, 1H), 2.70-2.80 (m, 2H), 2.85-2.95 (m, 1H), 3.00 (s, 2H), 3.12 (s, 3H), 3.33 (s, 2H), 5.072 (q, J = 9.2 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H), 7.27 (t, J =8 Hz, 1H), 7.55 (s, 1H), 7.63 (d, J = 8 Hz, 1H), 8.0 (d, J = 2 Hz, 1H), 8.21 (s, 1H), 8.48 (d, J = 2.4 Hz, 1H), 11.70 (s, 1H); ESI-MS (m/z) 545.2 (M+H) + The details of synthesis and analytical data of the examples synthesized from the above- mentioned methods are given below in Table-13. Table-13: Structure, method, intermediates used, chemical name and analytical data of Example (10-46) Example 47 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl -4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide Step-1: N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyc lobutyl)phenyl)-2-oxo- 1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3-carbo xamide To a stirred solution of 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 - carboxylic acid (1.15g, 4.653 mmol) in DMF (15 mL) was added HATU (2.12 g, 5.58 mmol) and stirred at room temperature for 30 min. To this mixture were added DIPEA (2.4 mL, 13.96 mmol) and 3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclob utyl)aniline (1.13 g, 4.653 mmol) and stirred for overnight. The reaction mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained residue was purified by flash column chromatography to yield 1.32 g of the desired compound. 1 HNMR (400 MHz, DMSO-d 6 ) δ 1.08 (d, J = 4.8 Hz, 3H), 2.50- 2.53 (m, 3H), 2.79-2.82(m, 2H), 3.16 (s, 3H), 5.08 (q, J = 8.8 Hz, 2H), 5.31 (d, J = 10.8 Hz, 1H), 5.76 (d, J = 3.6 Hz, 1H), 6.60-6.67 (m, 1H), 7.10 (d, J = 7.6Hz, 1H), 7.36-7.39 (m, 1H), 7.62-7.64 (m, 2H), 8.25 (s, 1H), 8.31 (s, 1H), 8.72 (d, J = 2.4 Hz, 1H), 11.69 (s, 1H); ESI-MS (m/z) 472.4 (M+H) + Step-2: 5-Formyl-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol -3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide To a stirred solution of N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl -1,2-dihydropyridine-3- carboxamide (5.8 g, 12.30 mmol) in THF/H 2 O (250 mL) were added NaIO 4 (5.53 g, 25.83 mmol) followed by 2.5% OsO 4 in t-BuOH (800 μl , 0.025 mmol). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to yield 4.72 g of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.08 (d, J = 4.8 Hz, 3H), 2.50-2.52(m, 3H), 2.81-2.83(m, 2H), 3.18 (s, 3H), 5.19 (q, J = 8.8 Hz, 2H), 7.13 (d, J = 7.6 Hz, 1H), 7.39 (t, J = 7.6 Hz, 1H), 7.86 (s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 8.30 (s, 1H), 8.75 (d, J = 2.0 Hz, 1H), 8.94 (s, 1H), 9.81 (s, 1H), 11.25 (s, 1H); ESI-MS (m/z) 474.3 (M+H) + Step-3: 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(4-methyl -4H-1,2,4-triazol-3- yl)cyclobutyl) phenyl)-2-oxo-1-(2,2,2-trifluoro ethyl)-1,2-dihydropyrid ine-3-carboxamide: To a stirred solution of 5-Formyl-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol -3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide( (3.6 g, 7.603 mmol) and isobutyl amine (2.78 g, 38.02 mmol) in 1,2, Dichloroethane (120 mL) was added acetic acid (1.37 gm, 22.81 mmol) and reflux for 4 h. Cooled the reaction mixture. To this reaction mixture was added sodium triacetoxy borohydride (4.83 gm, 22.81 mmol) portion wise and stirred at room temperature for overnight. The reaction mixture was quenched with aqueous bicarbonate solution and extracted twice with ethyl acetate. The organic layer was concentrated under reduced pressure and the obtained residue was purified by flash chromatography to yield 2.1 g of the desired product. 1 H NMR (400 MHz, DMSO-d6) δ 1 H NMR (400 MHz, DMSO-d6): δ 0.87 (d, J = 6.8Hz, 6H), 1.09 (d, J = 4.4 Hz, 3H), 1.66 -1.69 (m, 1H), 2.29 -2.30 (m, 2H), 2.50 - 2.52 (m, 3H), 2.80-2.82 (m, 2H), 3.18 (s, 3H), 3.58 (s, 2H), 5.11 (q, J = 8.4 Hz, 2H), 7.10 (d, J = 8.0 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.66 (d, J = 8 Hz, 1H), 8.02 (s, 1H), 8.30 (s, 1H), 8.57 (s, 1H), 11.84 (s, 1H); ESI-MS (m/z) 531.4 (M+H) + The details of synthesis and analytical data of the examples prepared from the above mentioned methods are given below in Table-14. The racemic compounds were prepared from the above mentioned methods and separated using SFC purification to obtain respective chiral isomers (Example 60 – 69). Table-14: Structure, chemical name, method, intermediate used and analytical data of Examples (48-94) Example 95 N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobu tyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-d ihydropyridine-3-carboxamide Step-1: N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobu tyl)phenyl)-2-oxo-1- (2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3-carboxa mide To a stirred solution of 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 - carboxylic acid (500 mg, 2.02 mmol) in DMF (10 mL) was added HATU (923 mg., 2.42 mmol) and stirred at room temperature for 30 min. To this mixture were added DIPEA (1.04 mL, 6.07 mmol), 3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobutyl )aniline (518 mg, 2.02 mmol) and stirred for overnight. The reaction mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated. The residue obtained was purified by flash column chromatography to yield 830 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.06 (s, 3H), 1.12 (s, 3H), 2.58 (d, J = 12.4Hz, 2H), 2.90 (d, J = 12.8Hz, 2H), 3.22 (s, 3H), 5.03 (q, J = 8.8 Hz, 2H), 5.30 (d, J = 10.8 Hz, 1H), 5.78 (d, J = 22.4 Hz, 1H), 6.60- 6.67 (m, 1H), 7.06 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.54-7.62 (m, 2H), 8.24 (d, J = 1.6 Hz, 1H), 8.32(s, 1H), 8.71 (s, 1H), 11.67 (s, 1H); ESI-MS (m/z) 486.3 (M+H) + Step-2: N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobu tyl)phenyl)-5-formyl-2- oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxami de To a stirred solution of N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl) cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1, 2-dihydropyridine-3-carboxamide (830 mg, 1.71 mmol) in THF (10.0 mL and H2O (5.0 mL) were added NaIO4 (733 mg, 3.42 mmol) followed by 1.0% OsO 4 in t-BuOH (0.017 mL , 0.007 mmol). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated to yield 710 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.05 (s, 3H), 1.13 (s, 3H), 2.58 (d, J = 12.4Hz, 2H), 2.90 (d, J = 12.4Hz, 2H), 3.23 (s, 3H), 5.18 (q, J = 8.8 Hz, 2H), 7.07 (d, J = 8.0 Hz, 1H), 7.36 (t, J = 8.1 Hz, 1H), 7.55 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H), 8.75 (d, J = 2.4 Hz, 1H), 8.95 (d, J = 2.0 Hz, 1H), 9.81 (s, 1H), 11.23 (s, 1H); ESI-MS (m/z) 488.2 (M+H) + Step-3: N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cyclobu tyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-d ihydropyridine-3-carboxamide To a stirred solution of N-(3-(3,3-dimethyl-1-(4-methyl-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-5-formyl-2-oxo-1-(2,2,2-trifluoroethyl )-1,2-dihydropyridine-3- carboxamide (100 mg, 0.20 mmol) and isobutylamine (72 mg, 0.61 mmol) in 1,2, dichloroethane (5.0 mL) was added drop of acetic acid and reflux for 4 h. The reaction mixture was brought to room temperature and then added sodium triacetoxy borohydride (130 mg, 0.61 mmol) portion wise and stirred at room temperature for overnight. The reaction mixture was quenched with aqueous bicarbonate solution and extracted twice with ethyl acetate. The organic layer was concentrated under reduced pressure and the obtained residue was purified by flash chromatography to yield 24 mg of the desired product. 1 HNMR (400 MHz, DMSO-d6) δ 0.86 (d, J =8.0 Hz, 6H), 1.05 (s, 3H), 1.12 (s, 3H), 1.61-1.71 (m, 1H), 2.27 (d, J =8.0 Hz, 2H), 2.57 (d, J =12.0 Hz, 2H), 2.89 (d, J =12.0 Hz, 2H), 3.22 (s, 3H), 3.56 (s, 2H), 5.08 (q, J =9.2 Hz, 2H), 7.04 (d, J =7.6 Hz, 1H), 7.35 (t, J =7.6 Hz, 1H), 7.56-7.58 (m, 2H), 7.99 (s, 1H), 8.32 (s, 1H), 8.56 (s, 1H), 11.82 (s,1H); ESI-MS (m/z) 545.3 (M+H) + The details of synthesis and analytical data of the examples prepared from the above mentioned methods are given below in Table-15. Table-15: Structure, chemical name, method, intermediate used and analytical data of Examples (96-151) Method D: Example-152 5-(1-(Isobutylamino)ethyl)-N-(3-((1s,3s)-3-methyl-1-(4-methy l-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide (Isomer-1) Example-153 5-(1-(isobutylamino)ethyl)-N-(3-((1s,3s)-3-methyl-1-(4-methy l-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide (Isomer-2) Step-1: Methyl 5-acetyl-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxylate To a stirred solution of methyl 5-bromo-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine-3 - carboxylate (800 mg, 2.539 mmol) in 1,4-Dioxane was degassed using N 2 for 15 min. Tributyl(1-ethoxyvinyl)tin (943 μL, 2.793 mmol) and Pd(PPh 3 ) 2 Cl 2 (89 mg, 0.126 mmol) were added to reaction mixture at room temperature under nitrogen atmosphere. The reaction mixture was heated to 120 o C for overnight in a sealed tube. The reaction mixture was cooled to room temperature and then 2 M HCl (40 ml) was added to reaction mixture and stirred for 1 hr at room temperature. The reaction mixture was quenched with aqueous bicarbonate solution and extracted twice with ethyl acetate. The organic layer was concentrated under reduced pressure and the obtained residue was purified by flash chromatography to yield 450 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 2.46 (s, 3H), 3.8 (s, 3H), 4.9-5.1 (m, 2H), 8.47 (d, J = 2.4 Hz, 1H), 8.92 (d, J = 2.4 Hz, 1H) Step-2: 5-Acetyl-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxylic acid To a stirred solution of 5-acetyl-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3- carboxylate (440 mg, 1.582 mmol) in THF/MeOH (10 mL) was added 2 mL of aqueous LiOH (199 mg, 4.748 mmol) and stirred at room temperature for overnight. The reaction mixture was concentrated and the residue obtained was diluted with water and acidified using 1N HCl solution and extracted twice with ethyl acetate. The organic layer was concentrated under reduced pressure and dried to yield 270 mg desired product. 1 H NMR (400 MHz, DMSO-d 6 ) δ 2.45 (s, 3H), 4.9- 5.2 (m, 2H), 8.57 (d, J = 2.4 Hz, 1H), 8.96 (d, J = 2.4 Hz, 1H), 13.03 (brs, 1H). Step-3: 5-Acetyl-N-(3-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triazol -3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide To a stirred solution of 5-acetyl-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3- carboxylic acid (225 mg, 0.852 mmol) in DMF (4 mL) was added HATU (388 mg, 1.022 mmol) and stirred at room temperature for 30 min. To this mixture were added DIPEA (440 μl, 2.556 mmol) and 3-(3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl) cyclobutyl)aniline (206 mg, 0.852 mmol) and stirred for overnight. The reaction mixture was diluted with water and extracted with DCM. The organic layer was dried over anhydrous sodium sulphate and concentrated. The obtained residue was purified by flash column chromatography to yield 191 mg of the desired compound. 1 H NMR (400 MHz, DMSO-d 6 ) δ 1.08(d, J = 5.2 Hz, 3H), 2.4- 2.55 (m, 3H), 2.53 (s, 3H), 3.1- 3.25 (m, 2H), 3.17 (s, 3H), 5.17 (q, J = 8.8 Hz, 2H), 7.12 (d, J = 8 Hz, 1H), 7.38 (t, J = 8 Hz, 1H), 7.59 (s, 1H), 7.66 (d, J = 8 Hz, 1H), 8.3 (s, 1H), 8.84 (d, J = 2.4 Hz, 1H), 8.99 (d, J = 2.4 Hz, 1H), 11.35 (s, 1H). 5-(1-(Isobutylamino)ethyl)-N-(3-((1s,3s)-3-methyl-1-(4-methy l-4H-1,2,4-triazol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide (Isomer-1) & 5-(1-(isobutylamino)ethyl)-N-(3-((1s,3s)-3-methyl-1-(4-methy l-4H-1,2,4- triazol-3-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethy l)-1,2-dihydropyridine-3- carboxamide (Isomer-2) To a stirred mixture of 5-acetyl-N-(3-(3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl) cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydr opyridine-3-carboxamide (100 mg, 0.205 mmol) and isobutyl amine hydrochloride (67 mg, 0.616 mmol) in THF were added triethylamine (288 μL, 2.05 mmol) and titanium isopropoxide (174 mg, 0.616 mmol) at room temperature. The reaction mixture was heated to 50 o C for 4 h. The reaction mixture was brought to room temperature and then added sodium cyanoborohydride (39 mg, 0.616 mmol) and stirred at room temperature for overnight. The reaction mixture was quenched with saturated NH 4 Cl solution and diluted with ethyl acetate. The reaction mixture was filtered. The organic layer was separated, concentrated and purified by flash chromatography to obtain 54 mg of the desired racemic product. The racemic product was purified by using SFC 0.1 % NH 3 in Methanol to yield 21 mg of the desired Isomer-1 and 23 mg of desired Isomer-2. Isomer-1: 1 HNMR (400 MHz, DMSO-d 6 ) δ 0.83 (d, J = 6.4 Hz, 6H), 1.08 (d, J = 5.2 Hz, 3H), 1.26 (d, J = 6.4 Hz, 3H), 1.4- 1.55 (m, 1H), 1.9- 2.1 (m, 1H), 2.1- 2.3 (m, 1H), 2.40- 2.55 (m, 3H), 2.65- 2.8 (m, 2H), 3.17 (s, 3H), 3.5- 3.65 (m, 1H), 5.02- 5.20 (m, 2H), 7.1 (d, J = 8 Hz, 1H), 7.37 (t, J = 8 Hz, 1H), 7.60- 7.80 (m, 2H), 8.02 (s, 1H), 8.3 (s, 1H), 8.61 (s, 1H), 11.83 (s, 1H); ESI-MS (m/z) 545.31(M+H) + Isomer-2: 1 HNMR (400 MHz, DMSO-d 6 ) δ 0.6- 0.8 (m, 6H), 1.08 (d, J = 4.8 Hz, 3H), 1.28 (d, J = 6.4 Hz, 3H), 1.5- 1.65 (m, 1H), 2- 2.15 (m, 1H), 2.2- 2.3 (m, 1H), 2.40 - 2.60 (m, 3H), 2.70- 2.85 (m, 2H), 3.17 (s, 3H), 3.60- 3.75 (m, 1H), 4.9- 5.2 (m, 2H), 7.1 (d, J = 8 Hz, 1H), 7.37 (t, J = 8 Hz, 1H), 7.60- 7.80 (m, 2H), 8.04 (s, 1H), 8.3 (s, 1H), 8.62 (s, 1H), 11.81 (s, 1H); ESI- MS (m/z) 545.3 (M+H) + The details of synthesis and analytical data of the examples prepared from the above mentioned methods are given below in Table-16. Table-16: Structure, chemical name, method, intermediate used and analytical data of Examples (154-155) Method E: Example-156 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(5-methyl -1H-imidazol-4-yl) cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydr opyridine-3-carboxamide N-(3-((1s,3s)-3-methyl-1-(5-methyl-1-trityl-1H-imidazol-4-yl )cyclobutyl)phenyl)-2- oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3-c arboxamide To a stirred solution of 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydropyridine-3 - carboxylic acid (0.3 g, 1.21 mmol) in DMF (5 ml) at 0 °C was added HATU (0.69 g, 1.82 mmol). After 30 min, 3-((1s,3s)-3-methyl-1-(5-methyl-1-trityl-1H-imidazol-4-yl) cyclobutyl)aniline (Intermediate A23) (0.587 g, 1.21 mmol) was added followed by DIPEA (0.47 g, 3.64 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was poured onto ice-cold water, precipitated solid was filtered and dried under vacuum to afford 0.8 g of the desired compound. ESI-MS (m/z) 713.3 (M+H) + 5-Formyl-N-(3-((1s,3s)-3-methyl-1-(5-methyl-1-trityl-1H-imid azol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide To a stirred solution of N-(3-((1s,3s)-3-methyl-1-(5-methyl-1-trityl-1H-imidazol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl -1,2-dihydropyridine-3- carboxamide (0.8 g, 1.21 mmol) in THF (20 ml) and water (4 ml) was added NaIO 4 (0.85 g, 3.36 mmol) followed by OsO 4 (1 % in t-BuOH, 0.0048 g, 0.0224 mmol, 0.5 ml). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was quenched with 10 % of sodium thiosulfate solution (25 mL) and extracted thrice with EtOAc. The organic layer was separated, dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to give crude compound. The crude compound was purified by combiflash chromatography to afford 0.550 g of the title compound. ESI-MS (m/z) 715.4 (M+H) + 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(5-methyl -1-trityl-1H-imidazol- 4-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-d ihydro pyridine-3-carboxamide To a stirred solution of 5-formyl-N-(3-((1s,3s)-3-methyl-1-(5-methyl-1-trityl-1H-imid azol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide (0.3 g, 0.41 mmol) in EDC (10 ml) was added isobutylamine (0.153 g, 2.09 mmol) and AcOH (0.125 g, 2.09 mmol) and heated at 80 °C for 3h. The reaction mixture was cooled to 0 °C, sodium triacetoxyborohydride (0.26 g, 1.25 mmol) was added and stirred at room temperature for 16 h. The reaction mixture was basified with sat. NaHCO 3 and extracted thrice with DCM. The organic layer was separated, dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to give crude compound. The crude compound was purified by combiflash chromatography to afford 0.17 g of the title compound. ESI-MS (m/z) 772 (M+H) + Step-4: 5-((Isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(5-methyl -1H-imidazol-4- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide To a stirred solution of 5-((isobutylamino)methyl)-N-(3-((1s,3s)-3-methyl-1-(5-methyl -1-trityl- 1H-imidazol-4-yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoro ethyl)-1,2-dihydropyridine-3- carboxamide (0.15 g, 0.1943 mmol) in MeOH (2 ml) at 0 °C was added 4M HCl in dioxane (3 ml) and heated at 80 °C for 3h. The reaction mixture was concentrated, basified with sat NaHCO 3 and extracted with EtOAc (3 x 25 ml). The organic layer was separated, dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to give crude compound. The obtained compound was purified by combiflash chromatography to afford 0.05 g of the title compound. 1 H NMR (DMSO-d 6 , 400 MHz) δ 0.89 (d, J = 4 Hz, 6H), 1.04 (d, J = 5.2 Hz, 3H), 1.75-1.85 (m, 1H), 1.91 (s, 3H), 2.32-2.34 (m, 3H), 2.46-2.50 (m, 2H), 2.74-2.79 (m, 2H), 3.77 (s, 2H), 5.09 (q, J = 9.0 Hz, 2H), 7.18 (d, J = 7.7 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 7.40 (s, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.66 (s, 1H), 8.12 (s, 1H), 8.65 (s, 1H), 11.72 (s, 1H); ESI-MS M/Z 530.4 (M+H) + The details of synthesis and analytical data of the examples prepared from the above mentioned methods are given below in Table-17. Table-17: Structure, chemical name, method, intermediate used and analytical data of Examples (157-160) Method F: Example-161 N-(3-acetamido-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-tria zol-3-yl)cyclobutyl)phenyl)-5- ((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-d ihydropyridine-3-carboxamide hydrochloride Step-1: Methyl 5-formyl-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihydropyridine- 3-carboxylate To a stirred solution of methyl 2-oxo-1-(2,2,2-trifluoroethyl)-5-vinyl-1,2-dihydro pyridine-3- carboxylate (0.5 g, 1.92 mmol) in THF (8 ml) and water (2 ml) was added NaIO 4 (0.82 g, 3.83 mmol) followed by OsO 4 (1 % in t-BuOH, 0.97 ml, 0.038 mmol). The reaction mixture was stirred at room temperature for 3 h. The reaction mixture was quenched with 10 % of sodium thiosulfate solution (25 ml) and partitioned between EtOAc (3 x 50 ml) and water (25 ml). The organic layer was separated, dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to afford 0.5 g of the title compound. ESI-MS (m/z) 264 (M+H) + Step-2: Methyl 5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2 -dihydropyridine- 3-carboxylate To a stirred solution of Methyl 5-formyl-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dihy dropyridine-3- carboxylate (0.5 g, 1.9 mmol) in DCE (10 ml) was added isobutylamine (0.94 ml, 9.5 mmol) and AcOH (0.53 ml, 9.5 mmol) and heated at 80 °C for 3h. The reaction mixture was cooled to 0 °C, sodium triacetoxy borohydride (1.2 g, 5.7 mmol) was added and stirred at room temperature for 16 h. The reaction mixture was basified with sat. NaHCO3 and extracted thrice with DCM. The organic layer was separated, dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to afford 0.52 g of the title compound. ESI-MS (m/z) 321 (M+H) + Methyl 5-(((tert-butoxycarbonyl)(isobutyl)amino)methyl)-2-oxo-1-(2, 2,2- trifluoroethyl)-1,2-dihydropyridine-3-carboxylate To a stirred solution of methyl 5-((isobutylamino)methyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2 - dihydropyridine-3-carboxylate (0.52 g, 1.62 mmol) in DCM (5 ml) was added trimethylamine (0.33 ml, 2.43 mmol) and (Boc) 2 O (0.55 ml, 2.43 mmol) and stirred at room temperature for 16 h. The organic solvent was evaporated under reduced pressure to obtain compound. The obtained compound was purified by combiflash chromatography to afford 0.16 g of the title compound. ESI-MS (m/z) 421 (M+H) + Step-4: 5-(((Tert-butoxycarbonyl)(isobutyl)amino)methyl)-2-oxo-1-(2, 2,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxylic acid To a stirred solution of methyl 5-(((tert-butoxycarbonyl)(isobutyl)amino)methyl)-2-oxo-1- (2,2,2-trifluoroethyl)-1,2-dihydropyridine-3-carboxylate (0.162 g, 0.38 mmol) in THF:MeOH:Water (1:1:0.5, 5 ml) was added lithium hydroxide (46 mg, 1.14 mmol) and stirred at room temperature for 16 h. The organic solvent was evaporated under reduced pressure. The obtained residue was acidified by 1N HCl solution and extracted with ethyl acetate (3 x 10 ml). The organic layer dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to obtain compound. The obtained compound was triturated with hexane solvent to afford 135 mg of the title compound. 1 H NMR (DMSO-d 6 , 400 MHz) δ 0.81 (d, J = 4 Hz, 6H), 1.40 (s, 9H), 1.86- 1.90 (m, 1H), 2.98-3.0 (m, 2H), 4.25 (s, 2H), 5.07 (q, J = 8 Hz, 2H), 8.09 (s, 1H), 8.39 (s, 1H), 13.8 (bs, 1H); ESI-MS (m/z) 407 (M+H) + Step-5: Tert-butyl ((5-((3-amino-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triaz ol-3- yl)cyclobutyl)phenyl)carbamoyl)-6-oxo-1-(2,2,2-trifluoroethy l)-1,6-dihydropyridin-3- yl)methyl)(isobutyl)carbamate To a stirred solution of 5-((1r,3r)-3-methyl-1-(4-methyl-4H-1,2,4-triazol-3-yl)cy clobutyl)benzene-1,3-diamine (Intermediate A8) (0.1 g, 0.389 mmol), 5-(((tert- butoxycarbonyl)(isobutyl)amino)methyl)-2-oxo-1-(2,2,2-triflu oroethyl)-1,2- dihydropyridine-3-carboxylic acid (0.0631 g, 0.155 mmol) in DMF (5 ml) was added 4- methylmorpholine (0.428ml, 3.89 mmol) and then 50% solution of T 3 P in DMF (0.371 ml, 0.583 mmol). The reaction mass was stirred at RT for 18 h. The reaction mass was diluted with brine solution (3 mL) and extracted with ethyl acetate (3 x 20 mL). The organic layer separated and dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to afford crude compound which was purified by column to obtain 57 mg of required product as yellow solid. ESI-MS (m/z) 646 (M+H) + Step-6: Tert-butyl ((5-((3-acetamido-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-t riazol-3- yl)cyclobutyl)phenyl)carbamoyl)-6-oxo-1-(2,2,2-trifluoroethy l)-1,6-dihydropyridin-3- yl)methyl)(isobutyl)carbamate To a stirred solution tert-butyl ((5-((3-amino-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-triaz ol- 3-yl)cyclobutyl)phenyl)carbamoyl)-6-oxo-1-(2,2,2-trifluoroet hyl)-1,6-dihydropyridin-3- yl)methyl)(isobutyl)carbamate (0.055g, 0.085 mmol) in DCM were added triethylamine (0.022 ml, 0.170 mmol) and then acetic anhydride (0.012 ml, 0.127 mmol). The reaction mass was stirred at room temperature for 18 hrs. The reaction mass was diluted with brine solution (3 ml) and extracted with DCM (3 x 10 ml). The combined organic layers were dried over anhydrous Na 2 SO 4 , evaporated under reduced pressure to result crude compound which was purified by column to afford 60 mg of the desired product. ESI-MS (m/z) 688 (M+H) + Step-7: N-(3-acetamido-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-tria zol-3- yl)cyclobutyl)phenyl)-5-((isobutylamino)methyl)-2-oxo-1-(2,2 ,2-trifluoroethyl)-1,2- dihydropyridine-3-carboxamide hydrochloride To a stirred solution N-(3-acrylamido-5-((1s,3s)-3-methyl-1-(4-methyl-4H-1,2,4-tri azol-3- yl)cyclobutyl)phenyl)-2-oxo-1-(2,2,2-trifluoroethyl)-1,2-dih ydropyridine-3-carboxamide (0.04 g) in DCM was added 4M hydrochloric acid in dioxane (1 ml) and was stirred at room temperature for 2 h. The solvent was evaporated under vacuum and the resulted solid was washed with diethyl ether and dried it to obtain 31 mg of required product as yellow solid. 1 H NMR (DMSO-d 6 , 400 MHz) δ 0.96 (d, J = 4 Hz, 6H), 1.10-1.09 (m, 3H), 2.08 (s, 3H), 2.59- 2.58 (m, 3H), 2.79-2.73 (m, 4H), 3.56 (s, 3H), 4.06-4.02 (m, 2H), 5.11 (q, J = 8 Hz, 2H), 7.35 (s, 1H), 7.41 (s, 1H), 8.04 (s, 1H), 8.32 (s, 1H), 8.78 (d, J = 4 Hz, 1H), 9.09 (bs, 2H), 9.18 (s, 1H), 10.17 (s, 1H), 11.66 (s, 1H); ESI-MS (m/z) 588 (M+H) + The details of synthesis and analytical data of the example prepared from the above mentioned methods are given below in Table-18. Table-18: Structure, chemical name, method, intermediate used and analytical data of Example- 162 The details of synthesis and analytical data of the examples synthesized from the above- mentioned methods are given below in Table-19. Table-19: Structure, method, intermediates used, chemical name and analytical data of Examples (163-205) PHARMACOLOGICAL ACTIVITY Cbl-b phosphorylation inhibition assay: The assay measures ability of test compounds to inhibit SRC kinase-mediated phosphorylation of a truncated version of His-tagged Cbl-b protein containing residues 36-427. This TR-FRET assay is performed in a 384 well plate at room temperature in a 10µl reaction volume with buffer containing 50mM HEPES pH 7.5, 5mM mgCl2, 1mM DTT, 0.1mg/ml BSA. Candidate compounds (1% DMSO final) were preincubated with 30nM Cbl-b (Accession number NP_733762.2) for one hour followed by an additional one hour in the presence of 30nM of GST-tagged SRC kinase (Accession number NP_005408.1) with 100µM ATP (final concentrations). Following, incubation, 10ul of a mixture containing 3.75nM Anti-His XL665 antibody (CisBio) and 1:200 TK-Cryptate Antibody (CisBio HTRF TK kit) prepared in detection buffer, was added to the reaction. The plate was incubated for one hour at room temperature followed by overnight in cold and fluorescence signal was measured with excitation of 337nm and dual emission of 665 and 620nm on Artemis HRTF reader. Signal was expressed as HTRF ratio (fluorescence intensity @665nm/fluorescence intensity @620nm x 10000). The resulting data were analysed and IC50 values were determined using nonlinear regression analysis, variable slope fitting (GraphPad Prism version 8.4.3). The IC 50 (nM) values of some of the compounds are set forth in Table-20 wherein “A” refers to an IC 50 value of less than 100 nM, “B” refers to IC 50 value in range of 100.01 to 500.0 nM, “C” refers to IC 50 value in range of 500.01 to 1000.0 nM and “D” refers to IC 50 values more than 1000.1 nM. Table-20: (-): Not determined Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as described above. All publications and patent applications cited in this application are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated herein by reference.
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