New sulfonamide derivatives

Abstract

The invention relates to a compound of formula (I), wherein R1 to R9 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

Description

[0001] F. Hoffmann-La Roche AG, CH-4070 Basel, Switzerland

[0002] Case: P39769

[0003] New sulfonamide derivatives

[0004] The present invention relates to organic compounds useful for therapy and / or prophylaxis in a mammal, and in particular to compounds that are TMEM175 enhancers. The compound of formula (I) is particularly useful in the treatment or prophylaxis of neurodegenerative diseases, fibrotic disorders or inflammatory disorders, more specifically, synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis and lysosomal storage disorders.

[0005] The invention relates in particular to a compound of formula (I)

[0006]

[0007] wherein

[0008] R1is hydrogen, alkyl or halogen;

[0009] R2is hydrogen or halogen;

[0010] R3is hydrogen or halogen;

[0011] R4is hydrogen, alkyl, halogen, alkoxy, alkoxyalkyl, hydroxyalkyl, haloalkyl, haloalkoxy, cycloalkyl, cycloalkoxy, halocycloalkylalkylamino or azetidinyl;

[0012] DP / 24.09.25 R5is hydrogen, halogen, hydroxyl or alkoxy;

[0013] R6is hydrogen or halogen;

[0014] R7is hydrogen, halogen or alkyl;

[0015] R8is hydrogen, halogen or alkoxy; and

[0016] R9is substituted phenyl, 2,3-dihydro-l,4-benzodioxyl, halothiophenyl, indolinone, alkylindolyl, alkylthiophenyl, dialkylthiophenyl, haloalkylthiophenyl, hydroxyalkylthiophenyl, haloalkenylthiophenyl, halocycloalkylthiophenyl, hydroxycycloalkylthiophenyl, alkylthiazolyl or alkylpyridinyl wherein substituted phenyl is phenyl substituted with one or two substituents selected from halogen, alkyl, alkoxy, haloalkoxyalkyl, alkyloxoamino and alkyloxoaminoalkyl or with one substituent selected from cycloalkyl, halocycloalkyl, halocycloalkylalkyl, halocycloalkylamino, haloalkylcycloalkylamino, halocycloalkoxy, haloalkyl, haloalkoxyalkyl, hydroxyalkyl, haloalkoxy, hydroxycycloalkyl, hydroxycycloalkylalkoxy, alkoxyalkyl, alkoxycycloalkyl, alkoxyhaloalkyl, alkinyl, dialkylamino, (halo)(cycloalkyl)alkyl, (halo)(cycloalkyl)alkoxy, cyanocycloalkyl, alkenyl, haloazetidinyl, haloalkylazetidinyl, alkoxyazetidinyl, alkoxyalkylazetidinyl, halopiperidinyl, quinolinyl, morpholinyl, alkoxypyrrolidinyl, tetrahydrofuranyl, (tetrahydrofuranyl) (alkyl) amino, oxazolylmethyl, pyrrolyl, haloalkoxycycloalkylamino, haloalkylcycloalkyloxy and haloalkylamino;

[0017] or a pharmaceutically acceptable salt thereof;

[0018] provided that

[0019] N-[4-[[[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl] amino] sulfonyl]phenyl] -acetamide;

[0020] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(trifluoromethoxy)-benzenesulfonamide;

[0021] 3,4-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;

[0022] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(trifluoromethyl)-benzenesulfonamide; 4-chloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0023] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(1-methylethyl)-benzenesulfonamide;

[0024] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-methoxy- benzenesulfonamide;

[0025] 3,4-difluoro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0026] 2-chloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0027] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-3,4-dimethoxy- benzenesulfonamide;

[0028] 3,5-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0029] 4-fluoro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0030] 4-(1,1-dimethylethyl)-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide; and

[0031] 2,4-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0032] are excluded.

[0033] TMEM175, or Transmembrane Protein 175, is a cation-selective lysosomal ion channel shown to conduct both potassium and proton currents (Hu M, Li P, Wang C, Feng X, Geng Q, Chen W, Marthi M, Zhang W, Gao C, Reid W, Swanson J, Du W, Hume RI, Xu H. Parkinson's disease-risk protein TMEM175 is a proton- activated proton channel in lysosomes. Cell 185: 2292-2308. e20, 2022). TMEM175 contributes to maintenance of the lysosomal membrane potential and stabilization of the lysosomal pH gradient both of which are crucial for proper lysosomal function (Cang, C.; Aranda, K.; Seo, Y.-J.; Gasnier, B.; Ren, D. TMEM175 Is an Organelle K+Channel Regulating Lysosomal Function. Cell 2015, 162, 1101-1112). Lysosomal catabolic activity is dependent upon a variety of enzymes confined to the lysosomal lumen. The majority of these enzymes exhibit pH dependent activity and are optimally functional at an acidic pH between 4.5 to 5.0 (Mellman I. Organelles observed: lysosomes. Science 244: 853-854, 1989. doi:

[0034] 10.1126 / science.244.4906.853). TMEM175 acts as a proton-activated channel that will preferentially expel protons from the lysosomal lumen at pH <4.5. At pH > 5.0, protondependent activation is reduced and the proton flux from the lumen to the cytosol is decreased, helping to maintain the optimal pH range for normal lysosomal function (Hu et al 2022, op. cit.). In mice, knockout of TMEM175 has been shown to reduce the enzymatic degradation of BSA and more specifically, the pH dependent activity of cathepsins B and D are reduced (Wie J, Liu Z, Song H, Tropea TF, Yang L, Wang H, Liang Y, Cang C, Aranda K, Lohmann J, Yang J, Lu B, Chen-Plotkin AS, Luk KC, Ren D. A growth-factor-activated lysosomal K+channel regulates Parkinson’s pathology. Nature 591: 431-437, 2021. doi: 10.1038 / s41586-021-03185-z).

[0035] TMEM175 has been identified as a novel lysosomal ‘leak-like’ potassium channel representing the major K+permeability of lysosomes (Cang et al., 2015, op. cit.).

[0036] TMEM175 is unique among other canonical potassium channels for several reasons: (1) no sequence homology with other tetrameric potassium channels, (2) it possesses a unique structure (Lee C, Guo J, Zeng W, Kim S, She J, Cang C, Ren D, Jiang Y. The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture. Nature. 2017 Jul 27;547 (7664):472-475; Oh S, Paknejad N, Hite RK. Gating and selectivity mechanisms for the lysosomal K+channel TMEM175. Elife. 2020 Mar 31;9:e53430) and assembles as a homodimer of 2 homologous copies of a six-transmembrane helix domain, where (3) the transmembrane helix 1 and 7 serve as the pore forming helix and (4) it is localized at lysosomal and endosomal membranes. Furthermore, TMEM175 is not blocked by cesium (Cs+) as are the majority of potassium channels, but instead can conduct Cs+with a similar permeability as K+. It has been shown to be blocked by 4-AP. Interestingly, TMEM175 is activated by growth factors via AKT in a kinase independent fashion (Wie et al., 2021, op. cit.).

[0037] In knockout studies, it has been shown that TMEM175 regulates lysosomal membrane potential, pH stability, and organelle fusion via potassium conductance on lysosomal and endosomal membranes (Cang et al, 2015, op. cit.).

[0038] TMEM175 with the M393T risk mutation is thought to be a (partial) loss of function mutation because measured currents are reduced (Wie et al., 2021, op. cit.) and the effect on lysosomal pH resembles that of knockout cells with a more alkaline pH during starvation. Furthermore, lysosomal localization of TMEM175 M393T might be reduced as compared to wildtype TMEM175 (Jinn S, Blauwendraat C, Toolan D, Gretzula CA, Drolet RE, Smith S, Nalls MA, Marcus J, Singleton AB, Stone DJ. Functionalization of the TMEM175 p. M393T variant as a risk factor for Parkinson disease. Hum Mol Genet. 2019 Oct l;28(19):3244-3254). In contrast to wildtype TMEM175, M393T overexpression does not reduce PFF-induced phospho a-synuclein (Jinn et al., 2019, op. cit.).

[0039] The Q65P variant is considered as a gain-of-function mutation under stress. When cells are starved, it leads to a reduction in TMEM175 current that is dependent and gated by AKT. In the Q65P mutant, the starvation-induced reduction in K+ current is delayed and early during starvation, the Q65P TMEM175 lysosomes carry a higher current than wildtype TMEM175. Taken together, these data suggest that the Q65P mutation represents a gain-of-function mutation under stress (Wie et al., 2021, op. cit.).

[0040] Dysfunction in lysosomal activities is linked to various neurodegenerative diseases, including Parkinson's disease, suggesting a potential role for TMEM175 in neurodegenerative disorders (Bahr B. A., Bendiske J. The neuropathogenic contributions of lysosomal dysfunction. J. Neurochem. 2002;83:481-489). Consistent with this hypothesis, TMEM175 has been identified by genome- wide association studies as a genetic risk factor for Parkinson’s disease (PD) (Hopfner F, Mueller SH, Szymczak S, Junge O, Tittmann E, May S, Eohmann K, Grallert H, Eieb W, Strauch K, Miiller-Nurasyid M, Berger K, Schormair B, Winkelmann J, Mollenhauer B, Trenkwalder C, Maetzler W, Berg D, Kasten M, Klein C, Hbglinger GU, Gasser T, Deuschi G, Franke A, Krawczak M, Dempfle A, Kuhlenbaumer G. Rare variants in specific lysosomal genes are associated with Parkinson’s disease. Mov Disord 35: 1245-1248, 2020. doi: 10.1002 / mds.28037), Rapid-eye-movement (REM) sleep behavior disorder (RBD) (Krohn E, et al. Genetic, structural, and functional evidence link TMEM175 to synucleinopathies. Ann. Neurol. 2020;87:139-153. doi: 10.1002 / ana.25629) and Dementia with Lewy Bodies (Chia R, Sabir MS, Bandres-Ciga S, et al.; American Genome Center. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat Genet. 2021;53(3):294-303). Multiple coding variants of TMEM175 have been identified and one variant, TMEM175 M393T, is associated with an increased risk and earlier onset of Parkinson’s disease (Blauwendraat C., Heilbron K., Vallerga C. L., Bandres-Ciga S., von Coelln R., Pihlstrom L., Simon-Sanchez J., Schulte C., Sharma M., Krohn L. et al. (2019) Parkinson's disease age at onset genome- wide association study: defining heritability, genetic loci, and alpha- synuclein mechanisms. Mov. Disord., 34, 866-875). Functional analysis of M393T indicated that M393T is a partial loss of function allele, suggesting that enhancement of TMEM175 activity could provide a therapeutic benefit in Parkinson’s disease (Jinn S, Drolet RE, Cramer PE, Wong AH, Toolan DM, Gretzula CA, Voleti B, Vassileva G, Disa J, Tadin-Strapps M, Stone DJ. TMEM175 deficiency impairs lysosomal and mitochondrial function and increases alpha-synuclein aggregation. Proc Natl Acad Sci USA 114: 2389-2394, 2017. doi:

[0041] 10.1073 / pnas.1616332114).

[0042] TMEM175 has also been identified as a comorbid gene between Amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (Tian Y, Ma G, Li H, Zeng Y, Zhou S, Wang X, Shan S, Xu Y, Xiong J, Cheng G. Shared Genetics and Comorbid Genes of Amyotrophic Lateral Sclerosis and Parkinson's Disease. Mov Disord. 2023 Oct;38(10):1813-1821. doi: 10.1002 / mds.29572. Epub 2023 Aug 3) and as a shared genetic risk loci among Alzheimer’s disease related dementias, Parkinson’s disease and Amyotrophic lateral sclerosis (Wainberg, M., Andrews, S. J. & Tripathy, S J. Shared genetic risk loci between Alzheimer’s disease and related dementias, Parkinson’s disease, and amyotrophic lateral sclerosis. Alz Res Therapy 15, 113 (2023)). Further, in a proteome-wide association study (PWAS) for Amyotrophic lateral sclerosis, TMEM175 was identified (Ma, Y., Jia, T., Qin, F. et al. Abnormal Brain Protein Abundance and Cross-tissue mRNA Expression in Amyotrophic Lateral Sclerosis. Mol Neurobiol 61, 510-518 (2024)) and lysosomal dysfunction is an important pathogenic disease mechanism in ALS (Root J, Merino P, Nuckols A, Johnson M, Kukar T. Lysosome dysfunction as a cause of neurodegenerative diseases: Lessons from frontotemporal dementia and amyotrophic lateral sclerosis.

[0043] Neurobiol Dis. 2021 Jul;154:105360). Therefore, TMEM175 enhancers may address the underlying disease biology in ALS.

[0044] Lysosomal storage disorders (Platt FM, d'Azzo A, Davidson BL, Neufeld EF, Tifft CJ. Publisher Correction: Lysosomal storage diseases. Nat Rev Dis Primers. 2019 May 17;5( 1):34) are characterized by accumulation of substrates in excess in lysosomes, often resulting from defects in lysosomal function. Since TMEM175 knockout leads to a reduced lysosomal hydrolysis activity and degradation activity (Hu et al 2022, op. cit.), a TMEM175 enhancer may increase lysosomal degradation capacity and thereby reduce pathological storage in lysosomal storage disorders.

[0045] In the present description the term “alkyl”, alone or in combination, signifies a straight-chain or branched-chain alkyl group with 1 to 8 carbon atoms, particularly a straight or branched-chain alkyl group with 1 to 6 carbon atoms and more particularly a straight or branched-chain alkyl group with 1 to 4 carbon atoms. Examples of straightchain and branched-chain Ci-Cs alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.-butyl, the isomeric pentyls, the isomeric hexyls, the isomeric heptyls and the isomeric octyls, particularly methyl, ethyl, propyl, butyl and pentyl more particularly methyl, ethyl, propyl, isopropyl, isobutyl, tert.-butyl and isopentyl. Particular examples of “alkyl” are methyl, ethyl and isopropyl. The term “cycloalkyl”, alone or in combination, signifies a cycloalkyl ring with 3 to 8 carbon atoms and particularly a cycloalkyl ring with 3 to 6 carbon atoms. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, cycloheptyl and cyclooctyl. Particular “cycloalkyl” are cyclopropyl and cyclobutyl.

[0046] The term “oxy”, alone or in combination, signifies the -O- group.

[0047] The term “alkyloxy” or “alkoxy”, alone or in combination, signifies a group of the formula alkyl-O- in which the term "alkyl" has the previously given significance, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec.butoxy and tert.butoxy. Particular examples of “alkyloxy” or “alkoxy” are methoxy and isopropoxy. Particular examples of “alkyloxy” or “alkoxy” are methoxy and propoxy, more particularly methoxy.

[0048] The term “cycloalkyloxy” or “cycloalkoxy”, alone or in combination, signifies a group of the formula cycloalkyl-O- in which the term "cycloalkyl" has the previously given significance, such as cyclopropoxy and cyclobutoxy. A particular example of “cycloalkoxy” is cyclopropoxy.

[0049] The terms “halogen” or “halo”, alone or in combination, signifies fluorine, chlorine, bromine or iodine and particularly fluorine, chlorine or bromine, more particularly fluorine and chlorine. The term “halo”, in combination with another group, denotes the substitution of said group with at least one halogen, particularly substituted with one to five halogens, particularly one to three halogens, i.e. one, two or three halogens. Particular halogens are fluorine, bromine and chlorine, more particularly fluorine and chlorine.

[0050] The term “haloalkyl”, alone or in combination, denotes an alkyl group substituted with at least one halogen, particularly substituted with one to five halogens, particularly one to three halogens. Particular “haloalkyl” are fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, fluoropropyl, difluoropropyl, and fluorobutyl.

[0051] The term “halocycloalkyl”, alone or in combination, denotes a cycloalkyl group substituted with at least one halogen, particularly substituted with one to three halogens. Particular “haloalkyl” are fluorocyclopropyl, chloropropyl, difluorocyclopropyl, fluorocyclobutyl and difluorocyclobutyl.

[0052] The term “haloalkoxy” or haloalkyloxy”, alone or in combination, denotes an alkoxy group substituted with at least one halogen, particularly substituted with one to five halogens, particularly one to three halogens. Particular “haloalkoxy” are difluoromethoxy, difluoroethoxy and trifluoroethoxy. The term “halophenyl”, alone or in combination, denotes a phenyl group substituted with at least one halogen, particularly substituted with one to three halogens. Particular “halophenyl” are chlorophenyl, fluorophenyl, (chloro)(fluoro)phenyl and dichlorophenyl.

[0053] The terms “hydroxyl” and “hydroxy”, alone or in combination, signify the -OH group.

[0054] The term “carbonyl”, alone or in combination, signifies the -C(O)- group.

[0055] The term “amino”, alone or in combination, signifies the primary amino group (-NH2), the secondary amino group (-NH-), or the tertiary amino group (-N-).

[0056] The term “cyano”, alone or in combination, signifies the -CN group.

[0057] The term “alkenyl”, alone or in combination, signifies a monovalent linear or branched hydrocarbon group of 2 to 7 carbon atoms, in particular 2 to 4 carbon atoms, with at least one double bond. Examples of alkenyl include ethenyl, propenyl, prop-2-enyl, isopropenyl, n-butenyl, i-butenyl, and t-butenyl. A particular examples of “alkenyl” is propenyl.

[0058] The term “alkynyl”, alone or in combination, signifies a monovalent linear or branched saturated hydrocarbon group of 2 to 7 carbon atoms, in particular from 2 to 4 carbon atoms, and comprising one, two or three triple bonds. Examples of alkynyl include ethynyl, propynyl, prop-2-ynyl, isopropynyl, n-butynyl, and iso-butynyl. A particular example of “alkynyl” is ethynyl.

[0059] The term “pharmaceutically acceptable salts” refers to those salts which retain the biological effectiveness and properties of the free bases or free acids, which are not biologically or otherwise undesirable. The salts are formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, particularly hydrochloric acid, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, N-acetylcystein. In addition these salts may be prepared from addition of an inorganic base or an organic base to the free acid. Salts derived from an inorganic base include, but are not limited to, the sodium, potassium, lithium, ammonium, calcium, magnesium salts. Salts derived from organic bases include, but are not limited to salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N-ethylpiperidine, piperidine, polyamine resins. The compound of formula (I) can also be present in the form of zwitterions. Particularly preferred pharmaceutically acceptable salts of compounds of formula (I) are the salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and methanesulfonic acid.

[0060] If one of the starting materials or compounds of formula (I) contain one or more functional groups which are not stable or are reactive under the reaction conditions of one or more reaction steps, appropriate protecting groups (as described e.g. in “Protective Groups in Organic Chemistry” by T. W. Greene and P. G. M. Wuts, 3rdEd., 1999, Wiley, New York) can be introduced before the critical step applying methods well known in the art. Such protecting groups can be removed at a later stage of the synthesis using standard methods described in the literature. Examples of protecting groups are tert-butoxycarbonyl (Boc), 9-fluorenylmethyl carbamate (Fmoc), 2-trimethylsilylethyl carbamate (Teoc), carbobenzyloxy (Cbz) and p-methoxybenzyloxycarbonyl (Moz).

[0061] The compound of formula (I) can contain several asymmetric centers and can be present in the form of optically pure enantiomers, mixtures of enantiomers such as, for example, racemates, mixtures of diastereoisomers, diastereoisomeric racemates or mixtures of diastereoisomeric racemates.

[0062] The term “asymmetric carbon atom” means a carbon atom with four different substituents. According to the Cahn-Ingold-Prelog Convention an asymmetric carbon atom can be of the “R” or “S” configuration.

[0063] The invention relates in particular to a compound of formula (I) as defined above wherein

[0064] R1is hydrogen, alkyl or halogen;

[0065] R2is hydrogen or halogen;

[0066] R3is hydrogen or halogen;

[0067] R4is hydrogen, alkyl, halogen, alkoxy, alkoxyalkyl, hydroxyalkyl, haloalkyl, haloalkoxy, cycloalkyl, cycloalkoxy, halocycloalkylalkylamino or azetidinyl;

[0068] R5is hydrogen, halogen, hydroxyl or alkoxy;

[0069] R6is hydrogen or halogen;

[0070] R7is hydrogen, halogen or alkyl; R8is hydrogen, halogen or alkoxy; and

[0071] R9is substituted phenyl, 2,3-dihydro-l,4-benzodioxyl, halothiophenyl, indolinone, alkylindolyl, alkylthiophenyl, dialkylthiophenyl, haloalkylthiophenyl, hydroxyalkylthiophenyl, haloalkenylthiophenyl, halocycloalkylthiophenyl, hydroxycycloalkylthiophenyl, alkylthiazolyl or alkylpyridinyl wherein substituted phenyl is phenyl substituted with one or two substituents selected from halogen, alkyl, alkoxy, haloalkoxyalkyl, alkyloxoamino and alkyloxoaminoalkyl or with one substituent selected from cycloalkyl, halocycloalkyl, halocycloalkylalkyl, halocycloalkylamino, haloalkylcycloalkylamino, halocycloalkoxy, haloalkyl, haloalkoxyalkyl, hydroxyalkyl, haloalkoxy, hydroxycycloalkyl, hydroxycycloalkylalkoxy, alkoxyalkyl, alkoxycycloalkyl, alkoxyhaloalkyl, alkinyl, dialkylamino, (halo)(cycloalkyl)alkyl, (halo)(cycloalkyl)alkoxy, cyanocycloalkyl, alkenyl, haloazetidinyl, haloalkylazetidinyl, alkoxyazetidinyl, alkoxyalkylazetidinyl, halopiperidinyl, quinolinyl, morpholinyl, alkoxypyrrolidinyl, tetrahydrofuranyl, (tetrahydrofuranyl) (alkyl) amino, oxazolylmethyl and pyrrolyl;

[0072] or a pharmaceutically acceptable salt thereof;

[0073] provided that

[0074] N-[4-[[[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl] amino] sulfonyl]phenyl] -acetamide;

[0075] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(trifluoromethoxy)-benzenesulfonamide;

[0076] 3,4-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;

[0077] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(trifluoromethyl)-benzenesulfonamide;

[0078] 4-chloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;

[0079] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(1-methylethyl)-benzenesulfonamide; N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-methoxy- benzenesulfonamide;

[0080] 3,4-difluoro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0081] 2-chloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0082] N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-3,4-dimethoxy- benzenesulfonamide;

[0083] 3,5-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0084] 4-fluoro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0085] 4-(1,1-dimethylethyl)-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide; and

[0086] 2,4-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;

[0087] are excluded.

[0088] The invention further relates to:

[0089] A compound of formula (I) wherein R1is hydrogen, methyl or chlorine;

[0090] A compound of formula (I) wherein R2is hydrogen or fluorine;

[0091] A compound of formula (I) wherein R3is hydrogen;

[0092] A compound of formula (I) wherein R4is hydrogen, alkyl, halogen, alkoxy, haloalkyl, haloalkoxy or cycloalkoxy;

[0093] A compound of formula (I) wherein R4is hydrogen, methyl, fluorine, chlorine, methoxy, fluoromethyl, difluoroethyl, difluoroethoxy or cylcopropyloxy;

[0094] A compound of formula (I) wherein R5is hydrogen or alkoxy;

[0095] A compound of formula (I) wherein R5is hydrogen or methoxy; A compound of formula (I) wherein R5is methoxy;

[0096] A compound of formula (I) wherein R6is hydrogen;

[0097] A compound of formula (I) wherein R7is hydrogen;

[0098] A compound of formula (I) wherein R8is hydrogen or halogen;

[0099] A compound of formula (I) wherein R8is hydrogen or fluorine;

[0100] A compound of formula (I) wherein R9is substituted phenyl, 2,3-dihydro-1,4-benzodioxyl, alkylthiophenyl, dialkylthiophenyl, haloalkylthiophenyl halocycloalkylthiophenyl or hydroxyalkylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent selected from alkyl, haloalkyl, halocycloalkyl, hydroxycycloalkyl, alkoxycycloalkyl, halocycloalkoxy, morpholinyl, haloalkoxyalkyl, cyanocycloalkyl, halocycloalkylamino, haloalkylcycloalkylamino, haloalkoxycycloalkylamino, haloalkylcycloalkyloxy and haloalkylamino;

[0101] A compound of formula (I) wherein R9is substituted phenyl, 2,3-dihydro-1,4-benzodioxyl, alkylthiophenyl, dialkylthiophenyl, haloalkylthiophenyl halocycloalkylthiophenyl or hydroxyalkylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent selected from alkyl, haloalkyl, halocycloalkyl, hydroxycycloalkyl, alkoxycycloalkyl, halocycloalkoxy, morpholinyl, haloalkoxyalkyl, cyanocycloalkyl, halocycloalkylamino and haloalkylcycloalkylamino;

[0102] A compound of formula (I) wherein R9is substituted phenyl, 2,3-dihydro-1,4-benzodioxyl, methylthiophenyl, dimethylthiophenyl, fluoromethylthiophenyl, difluoromethylthiophenyl, fluorocyclopropylthiophenyl or hydroxymethylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent selected from methyl, difluoroethyl, fluorocyclopropyl, hydroxycyclopropyl, methoxycyclopropyl, difluorocyclopropyl, morpholinyl, difluoromethoxymethyl, cyanocyclopropyl, difluorocyclopropyloxy, fluorocyclobutylamino, difluorocyclobutylamino, difluoromethylcyclobutylamino, difluoroethyloxycyclobutylamino, difluoromethylcyclobutyloxy and trifluoroethylamino;

[0103] A compound of formula (I) wherein R9is substituted phenyl, 2,3-dihydro-1,4-benzodioxyl, methylthiophenyl, dimethylthiophenyl, fluoromethylthiophenyl, difluoromethylthiophenyl, fluorocyclopropylthiophenyl or hydroxymethylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent selected from methyl, difluoroethyl, fluorocyclopropyl, hydroxycyclopropyl, methoxycyclopropyl, difluorocyclopropyl, morpholinyl, difluoromethoxymethyl, cyanocyclopropyl, difluorocyclopropyloxy, fluorocyclobutylamino, difluorocyclobutylamino and difluoromethylcyclobutylamino;

[0104] A compound of formula (I) wherein R9is substituted phenyl, 2,3-dihydro-1,4-benzodioxyl, methylthiophenyl, dimethylthiophenyl, fluoromethylthiophenyl, difluoromethylthiophenyl, fluorocyclopropylthiophenyl or hydroxymethylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent in para position to the sulfur atom to which it is attached, selected from methyl, difluoroethyl, fluorocyclopropyl, hydroxycyclopropyl, methoxycyclopropyl, difluorocyclopropyl, morpholinyl, difluoromethoxymethyl, cyanocyclopropyl, difluorocyclopropyloxy, fluorocyclobutylamino, difluorocyclobutylamino, difluoromethylcyclobutylamino, difluoroethyloxycyclobutylamino, difluoromethylcyclobutyloxy and trifluoroethylamino;

[0105] A compound of formula (I) wherein R9is substituted phenyl, 2,3-dihydro-1,4-benzodioxyl, methylthiophenyl, dimethylthiophenyl, fluoromethylthiophenyl, difluoromethylthiophenyl, fluorocyclopropylthiophenyl or hydroxymethylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent in para position to the sulfur atom to which it is attached, selected from methyl, difluoroethyl, fluorocyclopropyl, hydroxycyclopropyl, methoxycyclopropyl, difluorocyclopropyl, morpholinyl, difluoromethoxymethyl, cyanocyclopropyl, difluorocyclopropyloxy, fluorocyclobutylamino, difluorocyclobutylamino and difluoromethylcyclobutylamino;

[0106] A compound of formula (I) wherein R9is 2,3-dihydro-1,4-benzodioxyl, chlorophenyl, isopropylphenyl, (methoxy)(trifluoromethyl)phenyl, fluorophenyl, chlorothiophenyl, methylphenyl, cyclopropylphenyl, (methyl)(fluoro)phenyl, fluorophenyl, fluoropropylphenyl, bromothiophenyl, indolinone, trifluoromethylphenyl, (chloro)(fluoro)phenyl, difluoromethylphenyl, cyanophenyl, ethylphenyl, difhioromehtlthiophenyl, difluoroethylphenyl, methoxyphenyl, dimethylaminophenyl, fluorocyclopropylphenyl, methylthiophenyl, quinazolinyl, isopropenylphenyl, difluoroazetidinylphenyl, difluoropiperidinylphenyl, morpholinylphenyl, difluorocyclopropylphenyl, difluoroethoxyphenyl, fluorocyclopropylmethoxyphenyl, fluorobutylphenyl, difluoromehtylazetidinylphenyl, methoxyazetidinylphenyl, methoxypyrrolidinylphenyl, tetrahydrofuranlymethylaminophenyl, difluorocyclobutylphenyl, methoxymethylazetidinylphenyl, oxetanylphenyl, (trifluoromethyl)(acetamide)phenyl, dichlorophenyl, methylpyridinyl, difluoromethoxyphenyl, difluomethoxymethylphenyl, hydroxypropylphenyl, methoxypropylphenyl, trifluoroethoxyphenyl, cyanocyclopropylphenyl, difluoromethoxymethylphenyl, oxazolylmethylphenyl, methylindolyl, acetamidomethylphenyl, methoxydifluoropropylphenyl, difluorocyclopropylmethylphenyl, fluorocyclobutylphenyl, pyrrolylphenyl, difluoroethylthiophenyl, difluorocyclopropyloxyphenyl, fluoroethylthiophenyl, fluorocyclobutylaminophenyl, fluoromethylthiophenyl, hydroxymethylthiophenyl, dimethylthiophenyl, methylthiazolyl, fluorocyclopropylthiophenyl, difluoromethylthiophenyl, chlorocyclopropylthiophenyl, fluoropropenylthiophenyl, difluorocyclobutylaminophenyl, cyanocyclopropylphenyl, fluorocyclopropylthiophenyl, difluoromethoxymehtylphenyl, hydroxycyclopropylthiophenyl, cyanocyclopropylphenyl, hydroxycyclopropylphenyl, methoxycyclopropylphenyl, hydroxycyclobutylphenyl, hydroxycyclobutylmethoxyphenyl, difluoromethylcyclobutylaminophenyl, (methyl)(difluoromethoxymethyl)phenyl, difluoroethyloxycyclobutylaminophenyl, difluoromethylcyclobutyloxyphenyl, trifluoroethylaminophenyl or trifluoromethylcyclobutylaminophenyl; and

[0107] A compound of formula (I) wherein R9is 2,3-dihydro-1,4-benzodioxyl, methylphenyl, difluoroethylphenyl, fluorocyclopropylphenyl, methylthiophenyl, morpholinylphenyl, difluomethoxymethylphenyl, difluorocyclopropylphenyl, cyanocyclopropylphenyl, difluorocyclopropyloxyphenyl, fluorocyclobutylaminophenyl, fluoromethylthiophenyl, hydroxymethylthiophenyl, dimethylthiophenyl, difluoromethylthiophenyl, difluorocyclobutylaminophenyl, cyanocyclopropylphenyl, fluorocyclopropylthiophenyl, hydroxycyclopropylphenyl, methoxycyclopropylphenyl, difluoromethylcyclobutylaminophenyl, difluoroethyloxycyclobutylaminophenyl, difluoromethylcyclobutyloxyphenyl or trifluoroethylaminophenyl.

[0108] In the definition of R9, the substituent of the phenyl group is advantageously in para position to the sulfur atom when the phenyl is substituted by only one substituent. When the phenyl is substituted by two substituents, it is advantageous that at least one of the substiutents is in para position to the sulfur atom.

[0109] The invention relates in particular to a compound of formula (I) which is of formula (I-R)

[0110]

[0111] wherein R1to R9are as defined above; or a pharmaceutically acceptable salt thereof.

[0112] The asymmetric carbon atom bearing the R5substituent is thus advantageously of the (R) absolute configuration.

[0113] The invention further relates to a compound selected from

[0114] N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,3-dihydro-l,4-benzodioxine-6-sulfonamide;

[0115] N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide;

[0116] N-[6-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide;

[0117] N-[7 -fluoro-2- [methoxy(phenyl)methyl] -4-oxo-quinazolin-3-yl] -4-isopropyl-benzenesulfonamide;

[0118] N-[2-[(4-chlorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-4-methoxy-2-(trifluoromethyl)benzenesulfonamide;

[0119] 4-fhioro-N-[6-fhioro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0120] N-(2-benzyl-8-methyl-4-oxo-quinazolin-3-yl)-5-chloro-thiophene-2-sulfonamide;

[0121] N-[6,7-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide;

[0122] N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0123] 2-chloro-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0124] N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-4-cyclopropyl-benzenesulfonamide;

[0125] 5-chloro-N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide;

[0126] N-(2-benzyl-6-fhioro-4-oxo-quinazolin-3-yl)-3-fluoro-4-methyl-benzenesulfonamide;

[0127] N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide; N-[2-[(3,4-difluorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-4-fluoro-benzenesulfonamide;

[0128] 4-fluoro-N-[6-fluoro-2-[(3-fluoro-4-methyl-phenyl)methyl]-4-oxo-quinazolin-3-y 1] benzenesulfonamide;

[0129] N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide;

[0130] N-[6-chloro-2- [methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] -4-( 1 -fluoro- 1 -methyl-ethyl)benzene sulfonamide;

[0131] N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide;

[0132] 4-( 1 -fluoro- 1 -methyl-ethyl)-N- [2- [methoxy(phenyl)methyl] -5-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0133] 5-bromo-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide;

[0134] 5-chloro-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide;

[0135] N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide;

[0136] 5-chloro-N-[8-chloro-6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl] thiophene -2- sulfonamide;

[0137] N-(2-benzyl-6-fhioro-5-methyl-4-oxo-quinazolin-3-yl)-5-chloro-thiophene-2-sulfonamide;

[0138] N-[6-fluoro-2-[(4-fluorophenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-2-oxo-indoline-5- sulfonamide;

[0139] N-[6-fluoro-2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide;

[0140] N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide;

[0141] N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide;

[0142] N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-2-chloro-4-fluoro-benzenesulfonamide;

[0143] N-(2-benzyl-5-chloro-8-fluoro-4-oxo-quinazolin-3-yl)-4-chloro-benzenesulfonamide; 4-chloro-N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-y 1] benzenesulfonamide;

[0144] N-(2-benzyl-5-chloro-8-fluoro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide; N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-(difluoromethyl)benzene sulfonamide;

[0145] N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide;

[0146] N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-(difluoromethyl)benzenesulfonamide; N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-ethynyl-benzenesulfonamide; N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-ethyl-benzenesulfonamide;

[0147] N-[8-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-5-(difluoromethyl)thiophene-2-sulfonamide;

[0148] N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide;

[0149] N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0150] 4-(1,1-difluoroethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide;

[0151] 5-chloro-N-[8-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide;

[0152] N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0153] N-[6-fluoro-2-[fluoro(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0154] N-(2-benzyl-8-methyl-4-oxo-quinazolin-3-yl)-3-fluoro-benzenesulfonamide;

[0155] N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide; 4-(difluoromethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-y 1] benzenesulfonamide;

[0156] N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0157] N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(difluoromethyl)benzene sulfonamide;

[0158] 4-methoxy-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0159] 4-(dimethylamino)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0160] N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0161] N-[6-fluoro-2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0162] N-[6-fluoro-2-[(3-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0163] N-[5-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0164] N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methoxy-benzenesulfonamide;

[0165] 3-fluoro-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0166] N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0167] N-(6-fluoro-2-(methoxy(phenyl)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0168] N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methoxybenzenesulfonamide; N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0169] N-(6-fluoro-2-((2-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0170] N-(2-benzyl-8-methoxy-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide;

[0171] N-[2-[fluoro(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;

[0172] N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide;

[0173] N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;

[0174] N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide;

[0175] 4-(dimethylamino)-N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0176] N-[6-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide;

[0177] 4-(difluoromethyl)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0178] N-[5-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide;

[0179] 4-(dimethylamino)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0180] N-[2-[(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0181] N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0182] 4-(1,1-difluoroethyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide; N-[6-fluoro-2-[methoxy-(4-methoxyphenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0183] N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0184] N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0185] N-[8-(fluoromethyl)-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0186] N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]quinoline-6-sulfonamide;

[0187] N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-isopropenyl-benzenesulfonamide;

[0188] 4-(1-fluorocyclopropyl)-N-[8-methoxy-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0189] N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0190] N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0191] (R)-4-(3,3-difluoroazetidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;

[0192] (R)-4-(4,4-difluoropiperidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;

[0193] (R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-morpholinobenzene sulfonamide;

[0194] 4-(2,2-difluorocyclopropyl)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin- 3 (4H) -yl)benzenesulfonamide;

[0195] (R)-4-(2,2-difluoroethoxy)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin- 3 (4H) -yl)benzenesulfonamide; (R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((l-fluorocyclopropyl)methoxy)benzenesulfonamide;

[0196] N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(l-fluoro-2-methylpropyl)benzenesulfonamide;

[0197] (R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0198] (R)-4-(3-(difluoromethyl)azetidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;

[0199] (R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(3-methoxy azetidin- 1 -yl)benzenesulfonamide;

[0200] 4-(2,2-difluoroethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl] benzenesulfonamide;

[0201] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(3-methoxypyrrolidin- 1 -yl)benzenesulfonamide;

[0202] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-[methyl(tetrahydrofuran-3-yl)amino]benzenesulfonamide;

[0203] 4-(2,2-difluorocyclobutyl)-N - [6-fluoro-4-oxo-2- [(R)-methoxy(phenyl)methyl] quinazolin- 3-yl]benzenesulfonamide;

[0204] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-[3-(methoxymethyl) azetidin- 1 -yl] benzene sulfonamide;

[0205] N-[8-cyclopropyl-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]- 4-methyl-benzenesulfonamide;

[0206] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(oxetan-2-yl)benzenesulfonamide;

[0207] N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide;

[0208] N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide;

[0209] N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-2-(trifluoromethyl)benzenesulfonamide; N-[2-[(4-chlorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide;

[0210] N-[6-chloro-2-(m-tolylmethyl)-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide;

[0211] N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2-(trifluoromethyl)benzenesulfonamide;

[0212] N-[7-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide;

[0213] 4-isopropyl-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-y 1] benzenesulfonamide;

[0214] N-(2-benzyl-6-chloro-4-oxo-quinazolin-3-yl)-2-(trifluoromethyl)benzenesulfonamide; N-[2-[(4-chlorophenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide;

[0215] N-[5-methyl-2-(m-tolylmethyl)-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide;

[0216] N-[4-[(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)sulfamoyl]-3-(trifluoromethyl)phenyl] acetamide;

[0217] N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-fluoro-2-methyl-benzenesulfonamide; N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,6-dichloro-benzenesulfonamide;

[0218] N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-2-chloro-4-fluoro-benzenesulfonamide;

[0219] N-(2-benzyl-8-chloro-4-oxo-quinazolin-3-yl)-4-chloro-benzenesulfonamide;

[0220] N-(2-benzyl-8-chloro-5-fluoro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide;

[0221] 4-chloro-N-[5-chloro-2-[hydroxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0222] 2-chloro-N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0223] 4-(l,l-difluoroethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide; 5-bromo-N-[6-fluoro-2-[fluoro(phenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide;

[0224] N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylpyridine-2-sulfonamide;

[0225] 4-(difluoromethoxy)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;

[0226] N-[5-chloro-2-[hydroxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0227] 3-cyclopropyl-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;

[0228] 4-(dimethylamino)-N-(7-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;

[0229] 4-(dimethylamino)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide;

[0230] N-[6-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(l,l-difluoroethyl)benzenesulfonamide;

[0231] N-[6-fluoro-2- [(4-fluorophenyl)-methoxy-methyl] -4-oxo-quinazolin-3-yl] -4-( 1 -hydroxy- 1 -methyl-ethyl)benzenesulfonamide;

[0232] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(2-methoxypropyl)benzenesulfonamide;

[0233] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethoxy)benzenesulfonamide;

[0234] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0235] 4-(l-cyanocyclopropyl)-N-[6-fhioro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl] benzenesulfonamide;

[0236] 4-(difluoromethoxymethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide; N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(oxazol-2-ylmethyl)benzenesulfonamide;

[0237] N-[8-(fluoromethyl)-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0238] N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-methyl-4-oxo-quinazolin-3-yl]-l-methyl-indole-6-sulfonamide;

[0239] N-[8-(fluoromethyl)-4-oxo-2-[(S)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0240] N- [ [4- [ [6-fluoro-4-oxo-2- [(R)-methoxy(phenyl)methyl] quinazolin-3-yl] sulfamoyl]phenyl]methyl] acetamide;

[0241] N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2- sulfonamide;

[0242] N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;

[0243] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0244] 4-(2,2-difluoro-3-methoxy-propyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;

[0245] 4-(2,2-difluorocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;

[0246] N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0247] N-[8-[(3,3-difluorocyclobutyl)methylamino]-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0248] N-[8-(azetidin-l-yl)-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0249] 4-[(2,2-difluorocyclopropyl)methyl]-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide; N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxo-8-(2,2,2-trifluoroethyl)quinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0250] (R)-N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;

[0251] (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0252] (R)-N-(8-(2,2-difluoroethoxy)-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0253] N-[6,8-difhioro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(l-fluorocyclobutyl)benzenesulfonamide;

[0254] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-cyanocyclopropyl)benzenesulfonamide;

[0255] N-[8-chloro-6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(2,2-difluorocyclopropyl)benzenesulfonamide;

[0256] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0257] N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-(isopropoxymethyl)-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0258] N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0259] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide;

[0260] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(lH-pyrrol-2-yl)benzenesulfonamide;

[0261] (R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(2,2-difluoroethyl)thiophene-2-sulfonamide;

[0262] (R)-N-(8-cyclopropoxy-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(1-fluorocyclopropyl)benzenesulfonamide; (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;

[0263] (R)-N-(8-methoxy-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;

[0264] (R)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0265] (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;

[0266] 4-(2,2-difluorocyclopropoxy)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;

[0267] (S)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;

[0268] (S)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0269] 5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;

[0270] N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-3-methyl- lH-indole-6-sulfonamide;

[0271] N-(8-(2,2-difluoroethoxy)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0272] (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;

[0273] (R)-4-(1-fluorocyclopropyl)-N-(8-(fluoromethyl)-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;

[0274] N-(6,8-difluoro-2-((S)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide;

[0275] N-(6,8-difluoro-2-((R)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide; (R)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;

[0276] (S)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;

[0277] N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-5-(hydroxymethyl)thiophene-2-sulfonamide;

[0278] N-[8-(difluoromethyl)-2-[(S)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide;

[0279] N-[8-(difluoromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide;

[0280] N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide;

[0281] 4-( 1, 1 -difluoroethyl)-N- [8-(fluoromethyl)-2- [(R)-methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl]benzenesulfonamide;

[0282] N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide;

[0283] (R) -N- (2- ((4-fluorophenyl) (methoxy )methyl) - 8 -methoxy-4-oxoquinazolin- 3 (4H) -yl) -4-methylbenzenesulfonamide;

[0284] (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fluoromethyl)thiophene-2-sulfonamide;

[0285] (S)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fluoromethyl)thiophene-2-sulfonamide;

[0286] (S)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;

[0287] N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-3,5-dimethyl-thiophene-2-sulfonamide;

[0288] N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-2-methyl-thiazole-5 - sulfonamide; 5-(l-fluorocyclopropyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-y 1] thiophene -2- sulfonamide;

[0289] 4-(l-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] benzenesulfonamide;

[0290] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(difluoromethyl)thiophene-2-sulfonamide;

[0291] 5-(l-chlorocyclopropyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl] thiophene -2- sulfonamide;

[0292] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-[(E)-3-fluoroprop-l-enyl] thiophene-2- sulfonamide;

[0293] 4-[(3,3-difluorocyclobutyl)amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0294] N-[8-chloro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0295] 4-(1-cyanocyclopropyl)-N-[8-(2,2-difluoroethoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0296] 4-(1-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0297] 4-(l-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] benzenesulfonamide;

[0298] 4-(1-cyanocyclopropyl)-N-[8-(cyclopropoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0299] 4-(1-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0300] 4-(1-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0301] 5-(hydroxymethyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide; 5-(hydroxymethyl)-N-[6-fluoro-8-methyl -4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide;

[0302] (R)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;

[0303] 5-(l-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide;

[0304] N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(1-fluorocyclopropyl)thiophene-2-sulfonamide;

[0305] 5-(l-hydroxycyclopropyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide;

[0306] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(hydroxymethyl)thiophene-2- sulfonamide;

[0307] N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonamide;

[0308] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-hydroxycyclopropyl)benzenesulfonamide;

[0309] N-[8-chloro-6-fluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-( 1 -methoxycyclopropyl)benzenesulfonamide;

[0310] N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;

[0311] N-[8-chloro-6-fluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-( 1 -hydroxycyclopropyl)benzenesulfonamide;

[0312] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;

[0313] N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;

[0314] N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonamide; 4-( 1 -fluoro- 1 -methyl-ethyl)-N- [5-methyl-4-oxo-2- [(R) -methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;

[0315] 4-( 1 -fluoro- 1 -methyl-ethyl)-N- [5-methyl-4-oxo-2- [(S)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;

[0316] N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(lS*,2R*)-2-hydroxycyclobutyl] benzene sulfonamide;

[0317] N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(2-hydroxycyclobutyl)methoxy]benzenesulfonamide;

[0318] N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(lR*,2S*)-2-hydroxycyclobutyl] benzene sulfonamide;

[0319] 4-[[(ls,3s)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0320] 4-methyl-N-[8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl] benzenesulfonamide;

[0321] (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy )methyl) - 3 -methylbenzenesulfonamide;

[0322] (S)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy )methyl) - 3 -methylbenzenesulfonamide;

[0323] 4-[[(ls,3s)-3-(2,2-difluoroethoxy)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0324] 4-[[(lr,3r)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0325] 4-[(lr,3r)-3-(difluoromethyl)cyclobutoxy]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0326] N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethylamino)benzenesulfonamide;

[0327] N-[6-fluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin-3-yl]- 4-[[(lr,3r)-3-(trifluoromethyl)cyclobutyl]amino]benzenesulfonamide; 4-[[(lr,3r)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0328] 4-[[(ls,3s)-3-(2,2-difluoroethoxy)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0329] N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethylamino)benzene sulfonamide;

[0330] N-[6,8-difluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[[(lr,3r)-3-(trifluoromethyl)cyclobutyl]amino]benzenesulfonamide;

[0331] N-[6,8-difluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4- [[(lr,3r)-3-(trifluoromethyl)cyclobutyl]amino]benzenesulfonamide; and

[0332] N-[6-fluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin-3-yl]- 4-[[(lr,3r)-3-(trifluoromethyl)cyclobutyl]amino]benzenesulfonamide

[0333] or a pharmaceutically acceptable salt thereof.

[0334] The invention further relates to a compound of formula (I) selected from

[0335] N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,3-dihydro-l,4-benzodioxine-6-sulfonamide;

[0336] N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0337] N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0338] N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0339] N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0340] N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0341] N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide; N-[2-[(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0342] N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0343] 4-(1,1-difluoroethyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;

[0344] N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0345] (R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0346] 4-(2,2-difluoroethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-y 1] benzenesulfonamide;

[0347] N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide;

[0348] N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0349] 4-(difluoromethoxymethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;

[0350] N-[8-(fluoromethyl)-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;

[0351] N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2- sulfonamide;

[0352] N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2- sulfonamide;

[0353] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0354] 4-(2,2-difluorocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide; N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0355] (R)-N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;

[0356] (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0357] (R)-N-(8-(2,2-difluoroethoxy)-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0358] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-cyanocyclopropyl)benzenesulfonamide;

[0359] N-[8-chloro-6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(2,2-difluorocyclopropyl)benzenesulfonamide;

[0360] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0361] (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2-sulfonamide;

[0362] (R)-N-(8-methoxy-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;

[0363] (R)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0364] (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;

[0365] 4-(2,2-difluorocyclopropoxy)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;

[0366] N-(8-(2,2-difluoroethoxy)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;

[0367] (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide; N-(6,8-difluoro-2-((R)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide;

[0368] (R)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;

[0369] N-[8-(difluoromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide;

[0370] N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide;

[0371] (R) -N- (2- ((4-fluorophenyl) (methoxy )methyl) - 8 -methoxy-4-oxoquinazolin- 3 (4H) -yl) -4-methylbenzenesulfonamide;

[0372] (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fluoromethyl)thiophene-2-sulfonamide;

[0373] N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-3,5-dimethyl-thiophene-2-sulfonamide;

[0374] 4-(1-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0375] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(difluoromethyl)thiophene-2-sulfonamide;

[0376] 4-[(3,3-difluorocyclobutyl)amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0377] N-[8-chloro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;

[0378] 4-(1-cyanocyclopropyl)-N-[8-(2,2-difluoroethoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0379] 4-(1-cyanocyclopropyl)-N-[8-(cyclopropoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0380] 4-(1-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide; 4-(1-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0381] 5-(hydroxymethyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide;

[0382] (R)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;

[0383] 5-(1-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide;

[0384] N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(1-fluorocyclopropyl)thiophene-2-sulfonamide;

[0385] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-hydroxycyclopropyl)benzenesulfonamide;

[0386] N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;

[0387] N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;

[0388] N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonamide;

[0389] 4-[[(ls,3s)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0390] 4-[[(ls,3s)-3-(2,2-difluoroethoxy)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0391] 4-[[(lr,3r)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;

[0392] 4-[(lr,3r)-3-(difluoromethyl)cyclobutoxy]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide; and

[0393] N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethylamino)benzenesulfonamide;

[0394] or a pharmaceutically acceptable salt thereof. The following abbreviations are use in the present description:

[0395] ACN is acetonitrile

[0396] EtOAc / EA is ethyl acetate;

[0397] PE is petroleum ether

[0398] CDI is 1,1'-carbonyldiimidazole

[0399] DAST is diethylamino sulfur trifluoride;

[0400] Pd2(dba)3 is Tris(dibenzylideneacetone)dipalladium(0);

[0401] DIPEA is N, N-diisopropylethylamine;

[0402] DMA is dimethylacetamide;

[0403] DMF is N, N-dimethylformamide;

[0404] DMSO is dimethylsulfoxide

[0405] HATU is Hexafluorophosphate Azabenzotriazole Tetramethyl Uronium

[0406] LiHDMS is lithium Bis(trimethylsilyl)amide

[0407] NMP is N-Methylpyrrolidone;

[0408] NCS is N-Chlorosuccinimide

[0409] Ir[dF(CF3)ppy]2(dtbpy))PF6 is [4,4'-Bis(1,1-dimethylethyl)-2,2'-bipyridine-N1,N1']bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]Iridium(III) hexafluorophosphate Me-THF is 2-Methyltetrahydrofuran

[0410] Pd2(dba)3 is tris(dibenzylideneacetone)dipalladium(0)

[0411] Pd(dppf)Cl2 is 1,1'-bis(di-tert-butylphosphino)ferrocene Palladium dichloride Fe(TPP)Cl is Iron(tetraphenylporphyrinato) chloride

[0412] o / n is overnight;

[0413] RT is room temperature;

[0414] TBAF is tetrabutylammonium fluoride TLC is thin-layer chromatography;

[0415] CHO is chinese hamster ovary;

[0416] CMV is cytomegalovirus;

[0417] FBS is fetal bovine serum;

[0418] NEAA is non-essential amino acids;

[0419] HEPES is 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid;

[0420] NMDG is N-methyl-D-glucamine diatrizoate;

[0421] EGTA is ethylene glycol-bis(P-aminoethyl ether)-N, N, N’, N’ -tetraacetic acid; EDTA is ethylenediaminetetraacetic acid;

[0422] DPBS is Dulbecco’s phosphate-buffered saline;

[0423] mV is millivolt;

[0424] TEA is tetraethylammonium;

[0425] THF is tetrahydrofuran;

[0426] NADPH is nicotinamide adenine dinucleotide phosphate;

[0427] CLintis intrinsic clearance;

[0428] TCFH is tetramethylchloroformamidinium hexafluorophosphate;

[0429] NMI is N-Methylimidazole;

[0430] LED is light-emitting diodes;

[0431] CMV is cytomegalovirus;

[0432] FBS is fetal bovine serum;

[0433] HEPES is 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid;

[0434] NMDG is N-methyl-D-glucamine diatrizoate;

[0435] EGTA is ethylene glycol-bis(beta- aminoethyl ether)-N, N, N’, N’ -tetraacetic acid; DPBS is Dulbecco’s phosphate-buffered saline;;

[0436] mV is millivolt

[0437] DCPIB is 4-[(2-Butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro- 1-oxo- lH-inden-5-yl)oxy]butanoic acid; and

[0438] 4-AP is 4- aminopyridine.

[0439] The compound of formula (I) can be generated using any of the reaction conditions described below, and the decision on which route to use is based on intermediate availability. Certain conditions allow for the preparation of an enantiomerically pure compound, however with longer synthesis.

[0440] For more information on the general procedures, please refer to the embodiments relating to the process of making the compound of formula (I) or a pharmaceutically acceptable salt thereof as described herein.

[0441] H2NNH2·H2O EtOH, 80C

[0442]

[0443] Scheme 1: Synthesis of the compound of formula (I)

[0444] Treatment of 2-aminobenzoate 1 with either a carboxylic acid using TCFH, NMI in DMF or HATU, DIPEA in DMF, ACN or DMSO, or with an acyl chloride using a suitable base (DIPEA, NEta) in DCM or DMF leads to 2-amidobenzoate intermediate 2 (scheme 1). Preferred conditions are using TCFH and NMI in DMF at RT. The amide intermediate 2 can then be cyclized by reaction with hydrazine in EtOH at 80°C to form the 3-aminoquinazolin-4(3H)-one intermediate 3, which can then be reacted with sulfonyl chlorides in the presence of LiHMDS in THF at -78 °C to afford the desired sulfonamide of formula I.

[0445]

[0446] Scheme 2: Synthesis of the compound of formula (I) Alternatively, 2- aminobenzoic acid 4 can be reacted with phenyl acetic acid using TCFH, NMI in DMF or HATU, DIPEA in DMF or DCM, or with an acyl chloride using a suitable base (DIPEA, NEta) in DCM or DMF to form cyclized 2-amidobenzoic acid 5, which can then be reacted with hydrazine monohydrate in EtOH at 80C to form the 3-aminoquinazolin-4(3H)-one intermediate 3. The sulfonamide of formula I can then be formed by reaction with sulfonyl chloride using LiHMDS in THF at -78C (scheme 2).

[0447] N2H4·H2O EtOH, 80 °C

[0448] O

[0449] R9-S-CI II o LiHMDS THF, -78C

[0450]

[0451] Scheme 3: Synthesis of the compound of formula (I)

[0452] Alternatively, treatment of 2-amido-benzoic acid 5 with acetic anhydride at temperature between 50 to 120°C provide 4H-benzo[d][l,3]oxazin-4-one cyclized intermediate 6 (scheme 3). Further treatment with hydrazine in EtOH at 80C leads to the 3-aminoquinazolin-4(3H)-one intermediate 3, which can then be reacted with sulfonyl chloride in the presence of LiHMDS in THF at -78°C to afford the desired sulfonamide.

[0453] 4

[0454] 5

[0455] O H2N- NHBOC O R9-S-CI R9-S-NH PCI3 II o pyridine, AcN, 40C 6 NHBoc Me-THF, 80-100C

[0456]

[0457] Scheme 4: Synthesis of the compound of formula (I)

[0458] Alternatively, 2- aminobenzoic acid 4 can be reacted with phenyl acetic acid using TCFH, NMI in DMF or HATU, DIPEA in DMF or DCM, or with an acyl chloride using a suitable base (DIPEA, NEta) in DCM or DMF to yield 2-amido-benzoic acid intermediate 5. Subsequent reaction with sulfonyl Boc-hydrazide 7 and phosphorus trichloride in Me-THF, THF, 1,4-dioxane or 2,2-dimethyloxolane at 80 to 100C affords desired cyclized sulfonamide of Formula I (scheme 4). Alternatively, the unprotected sulfonyl hydrazide can be used for the cyclization step under the same conditions. H2N Ph b-p i =o Ph KOtBu, THF

[0459] 10

[0460]

[0461] Scheme 5: Synthesis of the compound of formula ( I)

[0462] Alternatively, reaction of 2- aminobenzamide 8 with acyl chloride in DCM at RT yields to amide intermediate 9, which can undergo cyclization to the quinazolin-4(3H)-one intermediate 10 by treatment with 10M NaOH in EtOH at RT (scheme 5). Subsequent treatment with amino diphenylphosphinate in presence of KOtBu in THF at 0°C then RT gives amine 11. Further treatment with methyl trifluoromethanesulfonate in presence of KOtBu at 0°C then RT affords the 3-aminoquinazolin-4(3H)-one intermediate 12, which can then be reacted with sulfonyl chloride in presence of LiHMDS in THF at -78 °C to afford the desired sulfonamide of Formula I. Pd2(dba)3, xantphos

[0463] DIPEA BnSH

[0464] Toluene, 100C

[0465] R

[0466] 13 14

[0467] NCS, AcOH

[0468] H2O, rt

[0469] i) nBuLi, THF, -78C, CI

[0470]

[0471] R9 XO

[0472] ii) SO2Cl2

[0473] 15

[0474] Scheme 6: Synthesis of sulfonyl chloride

[0475] Sulfonly chlorides can be prepared by cross -coupling reaction between (hetero)aryl bromide 13 and benzyl mercaptan to yield thioether intermediates 14. Preferred conditions are using Pd2(dba)3 with xantphos in presence of a suitable base like DIPEA at 100°C. Subsequent treatment with NCS and AcOH in water at rt yields the desired sulfonyl chlorides 15. Alternatively, aryl bromide 13 can be reacted with n-BuLi in THF at -78C followed by addition of SO2Cl2 to yield the desired sulfonyl chloride 15.

[0476] Buchwald-Hartwig amination

[0477]

[0478] R-COOH

[0479]

[0480] photoredox C-C

[0481]

[0482] bond formation

[0483]

[0484] Scheme 7: Late stage functionalization of iodobenzene sulfonamide

[0485] In scheme 7, NR’R” can be morpholine, 4,4-difluoropiperidin, 3,3-difluoroazetidine; 3-methoxyazetidine, 3 -methoxypyrrolidine, 3-(methoxymethyl)azetidine, N-methyltetrahydrofuran-3-amine, 3,3-difluorocyclobutan-1-amine or 3-fluorocyclobutan-1-amine. R can be 2-oxetane.

[0486] Late stage functionalization of iodobenzene sulfonamide 16 can be performed via Buchwald-Hartwig amination by reaction of an iodo-aryl intermediate with an amine (or its corresponding HC1 salt) in the presence of a Pd catalyst (such as Pd2(dba)3, a suitable base (such as Cs2CO3) and a phospine ligand (such as XPhos) in 1,4-dioxane at 100°C to yield aniline-based product 17 (scheme 7). Decarboxylative alkylation via photoredox catalysis can be performed by using iodobenzene sulfonamide 16 with carboxylic acid in the presence of a nickel catalyst and by irradiation with blue LED (450nm) to yield 18.

[0487] (X=l)

[0488]

[0489] Buchwald-Hartwig amination

[0490]

[0491]

[0492]

[0493] (X=Br, Y=OH, I) photoredox C-C bond formation

[0494]

[0495] Scheme 8: Late stage functionalization of aryl halide

[0496] In scheme 8, NR’R” can be (3,3-difluorocyclobutyl)methanamine or azetidine. R can be CF3or CHF2.

[0497] Fate stage functionalization of aryl halide intermediate can be performed via Buchwald-Hartwig amination by reaction of iodo-aryl intermediate 19 with an amine (or its corresponding HC1 salt) in the presence of a Pd catalyst (such as Pd2(dba)3and a phospine ligand (such as XPhos) in 1,4-dioxane at 100°C (scheme 8). Other means of late stage functionalization consist of photoredox cross-couping reaction using a bromo-aryl intermediate and a fluoro-alkyl (iodo- or alcohol) in the presence of a nickel catalyst and by irradiation with blue LED (450nm) to yield 21.

[0498] Isolation and purification of the compounds and intermediates described herein can be effected, if desired, by any suitable separation or purification procedure such as, for example, filtration, extraction, crystallization, column chromatography, thick-layer chromatography, preparative low or high-pressure liquid chromatography, supercritical fluid chromatography or a combination of these procedures. However, other equivalent separation or isolation procedures could, of course, also be used. Mixture of chiral compounds of formula (I) or intermediates can be separated using preparative chiral HPLC or SFC purifications. Chiral chromatography purifications were performed using the following conditions:

[0499] A Column: CHIRALPAK PAK AD-H, 30*250mm; Mobile Phase A: Hex(0.1% FA)— HPLC, Mobile Phase B: EtOH; Flow rate: 40 mL / min; Gradient: isocratic 50%

[0500] B Column: CHIRALPAK ID, 3*25 cm, 5 pm; Mobile Phase A: Hex(0.1% FA)— HPLC, Mobile Phase B: IPA; Flow rate: 40 mL / min; Gradient: isocratic 20%

[0501] C Column: CHIRALPAK-IK, 3*25mm, 5pm; Mobile Phase A: Hex(0.1% FA)— HPLC, Mobile Phase B: IPA; Flow rate: 40 mL / min; Gradient: isocratic 20%

[0502] D Column: CHIRALPAK IG, 3*25 cm, 5 pm; Mobile Phase A: CO2, Mobile Phase B: MEOH(0.1% 2M NH3-MEOH); Flow rate: 100 mL / min; Gradient: isocratic 25% B; Column Temperature(°C): 25; Back Pressure(bar): 100

[0503] E Column: CHIRALPAK IA, 3*25 cm, 5 pm; Mobile Phase A: Hex (0.1% FA)- -HPLC, Mobile Phase B: EtOH; Flow rate: 40 mL / min; Gradient: isocratic 20%

[0504] F Column: CHIRAL ART Cellulose-SC, 3*25 cm, 5 pm; Mobile Phase A:

[0505] Hex(0.1% FA)— HPLC, Mobile Phase B: EtOH; Flow rate: 40 mL / min;

[0506] Gradient: isocratic 10%

[0507] G Column CHIRALPAK IA, 3*25 cm, 5 pm; Mobile Phase A: MeOtBu (10 mM NH3-MeOH), Mobile Phase B: MEOH; Flow rate: 40 mL / min; Gradient: isocratic 25%

[0508]

[0509] H Column: CHIRAL ART Cellulose-SB 5*25 cm, 5 pm; Mobile Phase A: CO2, Mobile Phase B: IPA(20 mMNH3); Flow rate: 100 mL / min; Gradient: isocratic 50% B; Column Temperature (°C): 30; Back Pressure(bar): 100

[0510] I Column: CHIRALPAK IG, 5*25 cm, 10 pm; Mobile Phase A: CO2, Mobile Phase B: MeOH(20mM NH3.M); Flow rate: 200 mL / min; Gradient: isocratic 35% B; Column Temperature(20 °C): 30; Back Pressure(bar): 100

[0511] J Column: CHIRAL ART Amylose-C NEO, 2*25 cm, 5 pm; Mobile Phase A:

[0512] Hex(0.1% FA)-HPLC, Mobile Phase B: IPA; Flow rate: 20 mL / min; Gradient: isocratic 50%

[0513] K Column: CHIRAL ART Cellulose-SZ, 3*25 cm, 5 pm; Mobile Phase A: Hex (0.1% FA)-HPLC, Mobile Phase B: ETOH; Flow rate: 40 mL / min; Gradient: isocratic 20%

[0514] L Column: CHIRALPAK IE, 3*25 cm, 5 pm; Mobile Phase A: Hex (0.1% FA)- HPLC, Mobile Phase B: EtOH; Flow rate: 40 mL / min; Gradient: isocratic 10%

[0515] M Column: CHIRALPAK IG, 3*25 cm, 5 pm; Mobile Phase A: Hex (0.1% DEA)-HPLC, Mobile Phase B: EtOH-HPLC; Flow rate: 40 mL / min; Gradient (B%): isocratic 10%

[0516] N Column: Lux 5um Cellulose-2 3*25 cm, 5 pm; Mobile Phase A:

[0517] Hex(0.1%FA)— HPLC, Mobile Phase B: EtOH— HPLC; Flow rate: 40 mL / min; Gradient (B%): isocratic 30%

[0518]

[0519] The invention thus further relates to a process for the preparation of a compound of formula (I) comprising one of the following steps:

[0520] (a) The reaction of a compound of formula (A)

[0521]

[0522] in the presence of R9SO2C1 and a base; or

[0523] (b) The reaction of a compound of formula (B)

[0524]

[0525] in the presence of R9SO2NH-NHRp and PCl3;

[0526] wherein R1to R9are as defined above and wherein Rp is hydrogen or an amine protecting group.

[0527] In step (a), the base is advantageously a non-nucleophilic base, in particular a lithiated organosilicon base, more particularly LiHMDS.

[0528] Step (a) can advantageously be carried out in THF, for example at around -78°C.

[0529] Step (b) can advantageously be carried out in Me-THF, THF, 1,4-dioxane or 2,2-dimethyloxolane.

[0530] Step (b) can be carried out at a temperature comprised between around 80°C and 100°C.

[0531] The amine protecting group of step (b) can be for example a Boc group.

[0532] The invention further relates to:

[0533] A compound of formula (I) for use as therapeutically active substance; A pharmaceutical composition comprising a compound of formula (I) and a therapeutically inert carrier;

[0534] The use of a compound of formula (I) or N-(2-benzyl-6-fluoro-4-oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide for the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders;

[0535] The use of a compound of formula (I) or N-(2-benzyl-6-fluoro-4-oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide for the preparation of a medicament for the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders;

[0536] A compound of formula (I) or N-(2-benzyl-6-fluoro-4-oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide for use in the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders; and

[0537] A method for the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders, which method comprises administering an effective amount of a compound of formula (I) or N-(2-benzyl-6-fluoro-4-oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide to a patient in need thereof.

[0538] Another embodiment of the invention provides pharmaceutical compositions or medicaments containing the compounds of the invention and a therapeutically inert carrier, diluent or excipient, as well as methods of using the compounds of the invention to prepare such compositions and medicaments. In one example, compounds of formula (I) may be formulated by mixing at ambient temperature at the appropriate pH, and at the desired degree of purity, with physiologically acceptable carriers, i.e., carriers that are non-toxic to recipients at the dosages and concentrations employed into a galenical administration form. The pH of the formulation depends mainly on the particular use and the concentration of compound, but preferably ranges anywhere from about 3 to about 8. In one example, a compound of formula (I) is formulated in an acetate buffer, at pH 5. In another embodiment, the compounds of formula (I) are sterile. The compound may be stored, for example, as a solid or amorphous composition, as a lyophilized formulation or as an aqueous solution. Compositions are formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular mammal being treated, the clinical condition of the individual patient, the cause of the disorder, the site of delivery of the agent, the method of administration, the scheduling of administration, and other factors known to medical practitioners.

[0539] The compounds of the invention may be administered by any suitable means, including oral, topical (including buccal and sublingual), rectal, vaginal, transdermal, parenteral, subcutaneous, intraperitoneal, intrapulmonary, intradermal, intrathecal and epidural and intranasal, and, if desired for local treatment, intralesional administration. Parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal, or subcutaneous administration.

[0540] The compounds of the present invention may be administered in any convenient administrative form, e.g., tablets, powders, capsules, solutions, dispersions, suspensions, syrups, sprays, suppositories, gels, emulsions, patches, etc. Such compositions may contain components conventional in pharmaceutical preparations, e.g., diluents, carriers, pH modifiers, sweeteners, bulking agents, and further active agents.

[0541] A typical formulation is prepared by mixing a compound of the present invention and a carrier or excipient. Suitable carriers and excipients are well known to those skilled in the art and are described in detail in, e.g., Ansel, Howard C., et al., Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadelphia: Lippincott, Williams & Wilkins, 2004; Gennaro, Alfonso R., et al. Remington: The Science and Practice of Pharmacy. Philadelphia: Lippincott, Williams & Wilkins, 2000; and Rowe, Raymond C. Handbook of Pharmaceutical Excipients. Chicago, Pharmaceutical Press, 2005. The formulations may also include one or more buffers, stabilizing agents, surfactants, wetting agents, lubricating agents, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, glidants, processing aids, colorants, sweeteners, perfuming agents, flavoring agents, diluents and other known additives to provide an elegant presentation of the drug (i.e., a compound of the present invention or pharmaceutical composition thereof) or aid in the manufacturing of the pharmaceutical product (i.e., medicament).

[0542] The invention will now be illustrated by the following examples which have no limiting character. Examples

[0543] Example 1: N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,3-dihydro-l,4-benzodioxine-6-sulfonamide

[0544]

[0545] a) 2-methyl-6-(2-phenylacetamido) benzoic acid

[0546] A solution of 2-amino-6-methylbenzoic acid (0.98 g, 6.47 mmol, 1.00 equiv) in THF (15 mL) was treated with DIPEA (2.51 g, 19.41 mmol, 3.00 equiv) at room temperature for 5 min under nitrogen atmosphere followed by the addition of phenylacetyl chloride (1 g, 6.47 mmol, 1.00 equiv) dropwise at 0°C. The resulting mixture was stirred at room temperature for 2 h under air atmosphere. The reaction was poured into water at room temperature. The resulting mixture was extracted with EtOAc (3x10 mL). The combined organic layer was washed with water (3x10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (2:1) to afford 2-methyl-6-(2-phenylacetamido) benzoic acid (700 mg, 40.18%yield) as a white solid.

[0547] b) N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,3-dihydro-l,4-benzodioxine-6-sulfonamide

[0548] A solution of 2,3-dihydro-l,4-benzodioxine-6-sulfonohydrazide (128.24 mg, 0.56 mmol, 1.50 equiv) in THF (1 mL) was treated with 2-methyl-6-(2-phenylacetamido)benzoic acid (100 mg, 0.37 mmol, 1.00 equiv) at room temperature for 5 min under nitrogen atmosphere followed by the addition of trichloropho sphane (152.97 mg, 1.11 mmol, 3.00 equiv) dropwise at room temperature. The resulting mixture was stirred at 100°C for 2 h under nitrogen atmosphere. The reaction was quenched with sat. NH4CI (aq.) at 0°C. The resulting mixture was extracted with EtOAc (3x10 mL). The combined organic layer was washed with water (3x10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 10 min; detector, UV 254 nm. This resulted in N-(2-benzyl-5-methyl-4-oxoquinazolin-3-yl)-2,3-dihydro- 1,4-benzodioxine-6-sulfonamide (23.9 mg, 13.9%yield, 99.37%purity) as a white solid. LCMS (ESI) [M+H]+: 464.2. ’H NMR (300 MHz, DMSO-d6) δ 11.22 (s, 1H), 7.71 - 7.59 (m, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.36 - 7.22 (m, 6H), 7.22 - 7.10 (m, 2H), 6.98 (d, J = 8.5 Hz, 1H), 4.51 (d, J = 15.0 Hz, 1H), 4.36 - 4.18 (m, 4H), 4.03 (d, J= 15.2 Hz, 1H), 2.43 (s, 3H).

[0549] Example 2: N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide

[0550]

[0551] The title compound was obtained in analogy to Example 1 (19.1% yield) using 2-methyl-6-(2-phenylacetamido) benzoic acid and 2-chlorobenzenesulfonohydrazide. LCMS (ESI) [M+H]+: 440.0. ’H NMR (300 MHz, DMSO-d6, ppm) δ 11.71 - 11.28 (m, 1H), 7.89 -7.84 (m, 1H), 7.70 - 7.57 (m, 3H), 7.48 - 7.36 (m, 1H), 7.35 - 7.23 (m, 5H), 7.23 - 7.18 (m, 2H), 4.29 - 4.11 (m, 2H), 2.43 (s, 3H).

[0552] Example 3: N-[6-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide

[0553]

[0554] The title compound was obtained in analogy to Example 6 as a white solid (21.3% yield) using 3-amino-6-chloro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 4-isopropylbenzenesulfonyl chloride. LCMS (ESI, m / z): [M + H]+: 498.15. ’H NMR (400 MHz, DMSO-d6): δ 11.41 (s, 1H), 7.93 - 7.78 (m, 3H), 7.75 - 7.67 (m, 2H), 7.49 - 7.43 (m, 2H), 7.37 - 7.72 (m, 5H), 5.76 (s, 1H), 3.32 (s, 3H), 3.01 (m, 1H), 1.23 (d, J = 6.9 Hz, 6H). Example 4: N-[7-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide

[0555]

[0556] The title compound was obtained in analogy to Example 1 (11.2% yield) using 4-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and 4-isopropylbenzenesulfonohydrazide. LCMS (ESI) [M+H]+: 482.0, ’H NMR (300 MHz, DMSO-d6) δ 11.79 – 11.27 (m, 1H), 8.02 - 7.86 (m, 1H), 7.80 - 7.61 (m, 3H), 7.52 - 7.26 (m, 8H), 5.74 (s, 1H), 3.32 (s, 3H), 3.08 - 2.94 (m, 1H), 1.23 (d, J = 6.9 Hz, 6H).

[0557] Example 5: N-[2-[(4-chlorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-4-methoxy-2-(trifluoromethyl)benzenesulfonamide

[0558] ci

[0559]

[0560] °\

[0561] The title compound was obtained in analogy to Example 6 as a white solid (4.8% yield) using 3-amino-2-(4-chlorobenzyl)-6-fluoroquinazolin-4(3H)-one and 4-methoxy-2-(trifluoromethyl)benzenesulfonyl chloride. LC-MS (ES, m / z): [M+l] =542.1H NMR (300 MHz, DMSO-d6) δ 11.29 (s, 1H), 8.00 (d, J= 8.9 Hz, 1H), 7.69 (d, J= 6.6 Hz, 2H), 7.59 (d, J= 8.4 Hz, 1H), 7.42 - 7.22 (m, 6H), 4.41 - 4.11 (m, 2H), 3.92 (s, 3H).

[0562] Example 6: 4-fluoro-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide F

[0563]

[0564] a) methyl 5-fluoro-2-(2-(4-fluorophenyl)acetamido)benzoate

[0565] A solution of methyl 2-amino-5-fluorobenzoate (1.0 g, 5.9 mmol, 1 equiv) in DMF (10 mL) was treated with 2-(4-fluorophenyl)acetyl chloride (1.5 g, 8.8 mmol, 1.5 equiv) and EhN (1.8 g, 17.7 mmol, 3 equiv). The mixture was stirred for 1 h. The resulting mixture was extracted with EtOAc (20 mL). The combined organic layers were washed with NaCl(aq) (3 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (3:1) to afford methyl 5-fluoro-2-(2-(4-fhiorophenyl)acetamido)benzoate (700.0 mg, 38.8 % yield) as a white solid. LC-MS: (ES, m / z): [M+l] =306.

[0566] b) 3-amino-6-fluoro-2-(4-fluorobenzyl)quinazolin-4(3H)-one

[0567] A solution of methyl 5-fluoro-2-[2-(4-fluorophenyl)acetamido]benzoate (950.0 mg, 3.1 mmol, 1 equiv) in EtOH (5 mL) was treated hydrazine hydrate (5 mL). The resulting mixture was stirred for additional 1 h at 80 °C. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 3-amino-6-fluoro-2-(4-fluorobenzyl)quinazolin-4(3H)-one (600.0 mg, 67.1% yield) as a white solid. LC-MS (ES, m / z): [M+l] =288.

[0568] c) 4-fluoro-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0569] A solution of 3-amino-6-fluoro-2-(4-fluorobenzyl)quinazolin-4(3H)-one (100.0 mg, 0.3 mmol, 1 equiv) in THF (2 mL) was treated with LiHMDS (116.5 mg, 0.6 mmol, 2 equiv) at -78 °C under nitrogen atmosphere for 30 min by the addition of 4-fluorobenzenesulfonyl chloride (101.6 mg, 0.45 mmol, 1.5 equiv) at -78 °C. The resulting mixture was stirred for additional 1 h at -78 °C. The reaction was quenched with water (2 mL) at 0 °C. The resulting mixture was extracted with EtOAc (5 x 2 mL). Dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by re versed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1 % FA), 5 % to 70 % gradient in 30 min; detector, UV 254 nm. This resulted in title compound as a (33.5 mg, 21.6 % yield) white solid. LC-MS (ES, m / z): [M+l] =446. ’H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 7.90 - 7.80 (m, 2H), 7.75 - 7.68 (m, 2H), 7.57 (dd, J= 8.0, 2.1 Hz, 1H), 7.47 - 7.36 (m, 2H), 7.34 - 7.26 (m, 2H), 7.21 - 7.11 (m, 2H), 4.45 - 4.35 (m, 1H), 4.20 - 4.01 (m, 1H).

[0570] Example 7: N-(2-benzyl-8-methyl-4-oxo-quinazolin-3-yl)-5-chloro-thiophene-2-sulfonamide

[0571]

[0572] The title compound was obtained in analogy to Example 6 as a white solid (8.0% yield) using 3-amino-2-benzyl-5-methylquinazolin-4-one and 5-chlorothiophene-2- sulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 446.2.1H NMR (400 MHz, Chloroform-d) δ 7.88 (s, 1H), 7.59 - 7.52 (m, 1H), 7.49 (dd, J= 8.3, 1.5 Hz, 1H), 7.30 (d, J= 1.7 Hz, 1H), 7.26 - 7.09 (m, 6H), 6.79 (d, J = 4.2 Hz, 1H), 4.63 (d, J = 14.8 Hz, 1H), 4.09 (d, J = 14.9 Hz, 1H), 2.44 (s, 3H).

[0573] Example 8: N-[6,7-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide

[0574]

[0575] The title compound was obtained in analogy to Example 6 as a white solid (22.0% yield) using 3-amino-6,7-difluoro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 4-isopropylbenzenesulfonyl chloride. LCMS (ES, m / z): LCMS (ESI) [M + H]+: 500.20.1H NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 8.01 -7.79 (m, 2H), 7.72 (d, J= 8.1 Hz, 2H), 7.47 (d, J= 8.1 Hz, 2H), 7.35 (s, 5H), 5.74 (s, 1H), 3.30 (s, 3H), 3.05 - 2.95 (m, 1H), 1.23 (d, J = 6.9 Hz, 6H). Example 9: N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0576] F

[0577]

[0578] The title compound was obtained in analogy to Example 6 as a white solid (22.0% yield) using 3-amino-6-fluoro-2-(4-fluorobenzyl)quinazolin-4(3H)-one, p-toluenesulfonyl chloride. LC-MS: (ES, m / z): [M+l] =442. ’H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H), 7.77 - 7.63 (m, 4H), 7.62 - 7.54 (m, 1H), 7.38 (d, J= 8.2 Hz, 2H), 7.31 - 7.22 (m, 2H), 7.20 - 7.09 (m, 2H), 4.60 - 3.90 (m, 2H), 2.41 (s, 3H).

[0579] Example 10: 2-chloro-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide

[0580] ci

[0581]

[0582] The title compound was obtained in analogy to Example 6 as a white solid (16.4% yield) using 3-amino-2-[methoxy(phenyl)methyl]-5-methylquinazolin-4-one, 2-chlorobenzenesulfonyl chloride. LCMS (ESI, m / z): [M+ H]+: 470.05.1H NMR (300 MHz, DMSO-d6): δ 11.14 (s, 1H), 7.92 (d, J= 7.9 Hz, 1H), 7.74 - 7.61 (m, 3H), 7.56 - 7.46 (m, 2H), 7.43 - 7.27 (m, 6H), 5.76 (s, 1H), 3.32 (s, 3H), 2.50 (s, 3H).

[0583] Example 11: N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-4-cyclopropyl-benzenesulfonamide

[0584]

[0585] a) N-(2-benzyl-5-methyl-4-oxoquinazolin-3-yl)-4-bromobenzenesulfonamide

[0586] N-(2-benzyl-5-methyl-4-oxoquinazolin-3-yl)-4-bromobenzenesulfonamide was obtained in analogy to Example 6 as a white solid (32.9% yield) using 3-amino-2-benzyl-5-methylquinazolin-4-one, 4-bromobenzenesulfonyl chloride and LiHMDS. LC-MS (ESI, m / z): [M+ H]+: 484.0.

[0587] b) N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-4-cyclopropyl-benzenesulfonamide

[0588] A solution of N-(2-benzyl-5-methyl-4-oxoquinazolin-3-yl)-4-bromobenzenesulfonamide (200 mg, 0.413 mmol, 1 equiv) and cyclopropylboronic acid (70.9 mg, 0.826 mmol, 2 equiv) in 1,4-dioxane (8 mL) and H2O (2 mL) were added Cs2CO3 (269.0 mg, 0.826 mmol, 2 equiv) and Pd(dppf)Cl2 (5.9 mg, 0.008 mmol, 0.02 equiv). The mixture was stirred 3 hours at 120 °C under nitrogen atmosphere. The aqueous layer was extracted with ethyl acetate (40 mL). The combined organic and concentrated under reduced pressure to give crude product. The residue was purified by reverse phase separation column [Mobile Phase A: Water (0.3% NH4HCO3), Mobile Phase B: acetonitrile; Gradient: 0% B to 70% B in 30 min] to give the title compound (29.3 mg, 15.86% yield) as a white solid. LC-MS (ESI, m / z): [M+ H]+: 446.1. ’H NMR (400 MHz, DMSO-d6) δ 11.24 (s, 1H), 7.64 (t, J = 7.8 Hz, 1H), 7.57 (d, J= 8.3 Hz, 2H), 7.42 (d, J= 8.1 Hz, 1H), 7.36 - 7.18 (m, 8H), 4.51 (d, J= 15.1 Hz, 1H), 4.02 (d, J = 15.1 Hz, 1H), 2.34 (s, 3H), 2.02 (td, J = 8.5, 4.3 Hz, 1H), 1.07 (dd, J= 8.4, 2.3 Hz, 2H), 0.74 (s, 2H).

[0589] Example 12: 5-chloro-N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide

[0590]

[0591] The title compound was obtained in analogy to Example 6 as a white solid (15.6% yield) using 3-amino-2-[methoxy(phenyl)methyl]-8-methylquinazolin-4-one, 5-chlorothiophene-2-sulfonyl chloride. MS (ESIpos): m / z =476.00[M+H]+.1H NMR (400 MHz, DMSO-d6) δ 12.03 (d, J = 161.0 Hz, 1H), 7.73 (dd, J = 40.6, 7.4 Hz, 2H), 7.54 - 7.52 (m, 1H), 7.49 -7.33 (m, 6H), 7.26 (d, J = 4.2 Hz, 1H), 5.86 (d, J = 6.6 Hz, 1H), 3.45 - 3.42 (m, 3H) 2.64 (s, 2H), 2.25 (s, 1H).

[0592] Example 13: N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-3-fluoro-4-methyl-benzenesulfonamide

[0593]

[0594] The title compound was obtained in analogy to Example 6 as a white solid (19.6% yield) using 3-amino-2-benzyl-6-fluoroquinazolin-4(377)-one, 3-fluoro-4-methylbenzenesulfonyl chloride. LC-MS: (ES, m / z): [M+l] =442.10. ’H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 7.74 - 7.67 (m, 2H), 7.59 (dt, 7= 8.5, 1.8 Hz, 1H), 7.56 - 7.51 (m, 1H), 7.51 - 7.42 (m, 2H), 7.37 - 7.29 (m, 2H), 7.27 (dt, J= 8.0, 2.0 Hz, 3H), 4.36 - 4.20 (m, 2H), 2.33 (d, J = 1.9 Hz, 3H).

[0595] Example 14: N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide

[0596]

[0597] The title compound was obtained in analogy to Example 6 as a white solid (28.3% yield) using 3-amino-6-fluoro-2-(methoxy (phenyl) methyl) quinazolin-4(3H)-one, 4-isopropylbenzenesulfonyl chloride. LCMS (ESI) [M + H]+:482.05.1H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 7.95 -7.44 (m, 7H), 7.35 (d, 7= 4.6 Hz, 5H), 5.73 (s, 1H), 3.30 (s, 3H), 3.01 (m, 1H), 1.22 (d, 7= 6.9 Hz, 6H). Example 15: N-[2-[(3,4-difluorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-4-fluoro-benzenesulfonamide

[0598]

[0599] The title compound was obtained in analogy to Example 6 as a white solid (29.9% yield) using 3-amino-2-[(3,4-difluorophenyl) methyl]-6-fluoroquinazolin-4-one and 4-fluorobenzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 464.1. ’H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 7.89 – 7.81 (m, 2H), 7.77 - 7.66 (m, 2H), 7.61 - 7.55 (m, 1H), 7.42 (dd, J= 8.7, 5.7 Hz, 2H), 7.42 - 7.28 (m, 2H), 7.11 (t, J = 6.8 Hz, 1H), 4.39 (s, 1H), 4.25 (s, 1H).

[0600] Example 16: 4-fluoro-N-[6-fluoro-2-[(3-fluoro-4-methyl-phenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0601]

[0602] The title compound was obtained in analogy to Example 6 as a white solid (44.8% yield) using 3-amino-6-fluoro-2-[(3-fluoro-4-methylphenyl) methyl] quinazolin-4-one, 4-fluorobenzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 460.1. ’H NMR (400 MHz, DMSO-d6) δ 11.65 (s, 1H), 7.89 - 7.80 (m, 2H), 7.72 (dd, J= 6.8, 1.8 Hz, 2H), 7.57 (dt, J = 8.4, 1.7 Hz, 1H), 7.41 (t, J= 8.9 Hz, 2H), 7.23 (t, J= 8.0 Hz, 1H), 7.06 - 6.95 (m, 2H), 4.41 (s, 1H), 4.15 (s, 1H), 2.21 (d, J= 1.9 Hz, 3H).

[0603] Example 17: N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide

[0604]

[0605] The title compound was obtained in analogy to Example 6 as a white solid (41.6% yield) using 3-amino-2-benzyl-5-chloroquinazolin-4-one, 4-fluorobenzenesulfonyl chloride. LCMS (ESI, m / z): [M+ H]+: 444.1. ’H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 7.87 – 7.79 (m, 2H), 7.74 (t, J= 8.0 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.51 (d, J= 7.8 Hz, 1H), 7.41 (td, J= 9.2, 2.7 Hz, 2H), 7.33 (t, J= 7.5 Hz, 2H), 7.27 (d, J= 7.3 Hz, 3H), 4.46 (s, 1H), 4.10 (s, 1H).

[0606] Example 18: N-[6-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(l-fluoro- 1 -methyl-ethyl)benzenesulfonamide

[0607]

[0608] The title compound was obtained in analogy to Example 6 as a white solid (8.7% yield) using 3-amino-6-chloro-2-[methoxy(phenyl)methyl]quinazolin-4-one, 4-(2-fluoropropan-2-yl)benzenesulfonyl chloride. LCMS (ESI, m / z): [M + H]: 515.95. ’H NMR (300 MHz, DMSO-d6): δ 11.31 (s, 1H), 7.92 - 7.71 (m, 5H), 7.63 - 7.61(m, 2H), 7.42 - 7.32 (m, 5H), 5.84 (s, 1H), 3.37 (s, 3H), 1.74 (s, 3H), 1.67 (s, 3H).

[0609] Example 19: N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide

[0610]

[0611] The title compound was obtained in analogy to Example 6 as a white solid (10.2% yield) using 3-amino-2-benzyl-5-chloroquinazolin-4-one and 2-chlorobenzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 460.3. ’H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 7.87 – 7.91 (m, 1H), 7.76 -7.68 (td, 3H),7.67 -7.41 (td, 3H), 7.33 - 7.17 (d, 5H), 4.20 - 4.15 (s, 2H).

[0612] Example 20: 4-(l-fluoro-l-methyl-ethyl)-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0613]

[0614] The title compound was obtained in analogy to Example 6 as a white solid (16.6% yield) using 3-amino-2-[methoxy(phenyl)methyl]-5-methylquinazolin-4-one and 4-(2-fluoropropan-2-yl)benzenesulfonyl chloride. LCMS (ESI, m / z): [M + H]: 496.25.1H NMR (300 MHz, DMSO-d6): δ 11.10 (s, 1H), 7.80 (d, J= 8.2 Hz, 2H), 7.69 - 7.58 (m, 3H), 7.44 -7.33 (m, 6H), 7.26 (d, J = 7.4 Hz, 1H), 5.93 (s, 1H), 3.42 (s, 3H), 2.41 (s, 3H), 1.72 (s, 3H), 1.65 (s, 3H).

[0615] Example 21: 5-bromo-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide

[0616]

[0617] The title compound was obtained in analogy to Example 6 as a white solid (49.3% yield) using 3-amino-6-fluoro-2-[(4-fluorophenyl)methyl]quinazolin-4-one and 5-bromothiophene-2- sulfonyl chloride. MS (ESIpos): m / z = 512 [M+H]+. ’H NMR (400 MHz, DMSO-d6) δ 11.97 (s, 1H), 7.76 -7.61 (m, 3H), 7.45 (d, J= 4.1 Hz, 1H), 7.37 -7.27 (m, 3H), 7.21 - 7.09 (m, 2H), 4.27 (s, 2H).

[0618] Example 22: 5-chloro-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide

[0619] A

[0620]

[0621] The title compound was obtained in analogy to Example 6 as a white solid (87% yield) using 3-amino-6-fluoro-2-[(4-fluorophenyl)methyl]quinazolin-4-one and 5-chlorothiophene-2-sulfonyl chloride. MS (ESIpos): m / z = 468 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 11.99 (s, 1H), 7.77 - 7.69 (m, 2H), 7.69 - 7.63 (m, 1H), 7.52 (d, J = 4.1 Hz, 1H), 7.35 - 7.27 (m, 2H), 7.25 (d, J= 4.1 Hz, 1H), 7.21 - 7.11 (m, 2H), 4.28 (s, 2H).

[0622] Example 23: N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide

[0623]

[0624] a) 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid

[0625] A solution of 6-amino-3-fhioro-2-methylbenzoic acid (0.2 g, 1.18 mmol, 1 equiv) in DCM (10 mL) was treated with ω-phenylacetic acid (0.2 g, 1.77 mmol, 1.5 equiv) and DIPEA (0.5 g, 3.54 mmol, 3 equiv) HATU (0.7 g, 1.77 mmol, 1.5 equiv). The mixture was stirred for 2 h at 25 °C. The resulting mixture was concentrated under vacuum. The residue was purified by re versed-phase flash chromatography with the following conditions: column, C18 silica gel; moble phase, MeCN in water (10 mmol / L NH4HCO3), 10% to 50% gradient in 30 min; detector, UV 254 nm. This resulted in 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid (200 mg, 58.88% yield) as a white solid. MS (ESIpos): m / z = 288.10 [M+H]+.

[0626] b) N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide

[0627] A solution of 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid (100 mg, 0.348 mmol, 1 equiv) in 2,2-dimethyloxolane (5 mL) was treated with N'-(4-fluorobenzenesulfonyl)tert-butoxycarbohydrazide (202.1 mg, 0.696 mmol, 2 equiv) and phosphorus trichloride (143.4 mg, 1.044 mmol, 3 equiv) at 100 °C. The mixture was stirred for 2 h. The resulting mixture was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions column, C18 silica gel; mobile phase, MeCN in water (10 mmol / L NH4HCO3), 10% to 50% gradient in 20 min; detector, UV 254 nm. This resulted in N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide (87.6 mg, 56.48% yield) as a white solid. MS (ESIpos): m / z = 442.00 [M+H]+. 1H NMR (400 MHz, DMSO-d6) 5 11.53 (s, 1H), 7.82 (dd, J = 8.6, 5.1 Hz, 2H), 7.65 (t, J = 9.2 Hz, 1H),7.51 (dd, J = 8.9, 5.0 Hz, 1H), 7.41 (t, J = 8.8 Hz, 2H), 7.33 (t, J = 7.4 Hz, 2H), 7.27 (d, J = 7.6 Hz, 3H), 4.43 (s, 2H), 2.28 (d, J = 2.3 Hz, 3H).

[0628] Example 24: 5-chloro-N-[8-chloro-6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide

[0629]

[0630] The title compound was obtained in analogy to Example 6 as a white solid (16.4% yield) using 3-amino-8-chloro-6-fluoro-2-[(4-fluorophenyl) methyl] quinazolin-4-one and 5-chlorothiophene-2-sulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 502.1. ’H NMR (400 MHz, DMSO-d6) 6 12.11 (s, 1H), 8.10 (dd, J = 8.5, 2.9 Hz, 1H), 7.68 (dd, J= 8.1, 2.9 Hz, 1H), 7.55 (d, J= 4.0 Hz, 1H), 7.37 - 7.29 (m, 2H), 7.25 (d, J= 4.1 Hz, 1H), 7.22 - 7.12 (m, 2H), 4.31 (s, 2H). Example 25: N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-5-chloro-thiophene-2-sulfonamide

[0631]

[0632] The title compound was obtained in analogy to Example 23 as a white solid (24.3% yield) using 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid and N'-(5-chlorothiophen-2-ylsulfonyl)tert-butoxycarbohydrazide. MS (ESIpos): m / z = 463.95 [M+H]+.1H NMR (300 MHz, DMSO-d6) 8 11.88 (s, 1H), 7.68 (t, J= 9.2 Hz, 1H), 7.52 (dd, J= 12.1, 4.6 Hz, 2H), 7.40 - 7.28 (m, 2H), 7.32 - 7.21 (m, 4H), 4.24 (s, 2H), 2.41 (d, J= 2.4 Hz, 3H).

[0633] Example 26: N-[6-fluoro-2-[(4-fluorophenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-2-oxo-indoline-5-sulfonamide

[0634]

[0635] The title compound was obtained in analogy to Example 23 as a white solid (26.9% yield) using 3-fluoro-6-[2-(4-fluorophenyl)acetamido]-2-methylbenzoic acid and N'-(2-oxo-l,3-dihydroindol-5-ylsulfonyl)tert-butoxycarbohydrazide. MS (ESIpos): m / z = 497.10 [M+H]+. 1H NMR (400 MHz, DMSO-d6) 6 11.21 (s, 1H), 10.87 (s, 1H), 7.70 - 7.41 (m, 4H), 7.29 (dd, J = 8.4, 5.7 Hz, 2H),7.19 - 7.09 (m, 2H), 6.90 (dd, J = 8.3, 1.9 Hz, 1H), 4.28 (s, 2H), 3.47 (s, 2H), 2.28 (d, J = 2.3 Hz, 3H).

[0636] Example 27: N-[6-fluoro-2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide

[0637]

[0638] The title compound was obtained in analogy to Example 23 as a white solid (22.2% yield) using 5-fluoro-2-(2-methoxy-2-phenylacetamido)-3-methylbenzoic acid and N-(4-isopropylbenzenesulfonyl) tert-butoxycarbohydrazide. LC-MS (ESI, m / z): [M+ H]+: 496.1. ’H NMR (400 MHz, Methanol-d4) 67.74 - 7.66 (m, 2H), 7.49 - 7.41 (m, 3H), 7.40 -7.30 (m, 5H), 7.27 (dd, J= 8.3, 2.9 Hz, 1H), 6.01 (s, 1H), 3.51 (s, 3H), 2.99 (h, J = 6.9 Hz, 1H), 2.60 (s, 3H), 1.27 (dd, J= 6.9, 1.6 Hz, 6H).

[0639] Example 28: N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide

[0640]

[0641] The title compound was obtained in analogy to Example 23 as a white solid (34.4% yield) using 3,5-difluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and tert-butyl 2-((4-(trifluoromethyl)phenyl)sulfonyl)hydrazine-l -carboxylate. LC-MS: (ES, m / z): [M+l] =526. ’H NMR (400 MHz, DMSO-d6) 6 11.94 (s, 1H), 8.03 (d, J= 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 7.92 (s, 1H), 7.48 - 7.31 (m, 6H), 5.88 (s, 1H), 3.40 (s, 3H).

[0642] Example 29: N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide

[0643]

[0644] The title compound was obtained in analogy to Example 6 as a white solid (14.3% yield) using 3-amino-6-fluoro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 4-(trifluoromethyl)benzenesulfonyl chloride. MS (ESIpos): m / z = 508.05[M+H]+.1H NMR (400 MHz, DMSO-d6) δ 11.69 (s, 1H), 8.13 - 7.92 (m, 4H), 7.88 - 7.65 (m, 2H), 7.57 (dd, J = 8.4, 2.9 Hz, 1H), 7.48 - 7.25 (m, 5H), 5.90 (s, 1H), 3.41 (s, 3H).

[0645] Example 30: N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-2-chloro-4-fluoro-benzenesulfonamide

[0646]

[0647] F

[0648] The title compound was obtained in analogy to Example 6 as a white solid (6.03% yield) using 3-amino-2-benzyl-5-chloroquinazolin-4-one and 2-chloro-4-fluorobenzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 478.1. ’H NMR (400 MHz, DMSO-d6) 6 11.68 (s, 1H), 7.94 (dd, J = 9.0, 5.9 Hz, 1H), 7.80 - 7.69 (m, 2H), 7.58 - 7.49 (m, 2H), 7.40 - 7.31 (m, 1H), 7.36 - 7.28 (m, 2H), 7.30 - 7.21 (m, 3H), 4.21 (s, 2H).

[0649] Example 31: N-(2-benzyl-5-chloro-8-fluoro-4-oxo-quinazolin-3-yl)-4-chloro-benzenesulfonamide

[0650]

[0651] The title compound was obtained in analogy to Example 23 as a white solid (8.1% yield) using 6-chloro-3-fluoro-2-(2-phenylacetamido)benzoic acid and N'-(4-chlorobenzenesulfonyl)tert-butoxycarbohydrazide. MS (ESIpos): m / z =478.00[M+H]+.1H NMR (400 MHz, DMSO-d6) 6 11.70 (s, 1H), 7.79 - 7.75 (m, 2H), 7.69 (t, J= 9.2 Hz, 1H), 7.62 (d, J= 8.6 Hz, 2H), 7.51 (dd, J= 8.8, 4.4 Hz, 1H), 7.35 -7.24 (m, 5H), 4.30 (s, 2H).

[0652] Example 32: 4-chloro-N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0653]

[0654] The title compound was obtained in analogy to Example 6 as a white solid (41.7% yield) using 3-amino-8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 4-chlorobenzene sulfonyl chloride. LC-MS (ES, m / z): [M+l] = 507.02.1H NMR (300 MHz, DMSO-d6) 6 11.53 (s, 1H), 7.98 (dd, J = 8.5, 2.9 Hz, 1H), 7.90 - 7.79 (m, 2H), 7.70 - 7.55 (m, 3H), 7.49 (d, J = 2.1 Hz, 1H), 7.48 - 7.28 (m, 4H), 5.92 (s, 1H), 3.44 (s, 3H).

[0655] Example 33: N-(2-benzyl-5-chloro-8-fluoro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide

[0656]

[0657] The title compound was obtained in analogy to Example 23 as a white solid (6.1% yield) using 6-chloro-3-fluoro-2-(2-phenylacetamido)benzoic acid and N'-(2-chlorobenzenesulfonyl)tert-butoxycarbohydrazide. MS (ESIpos): m / z =478.00[M+H]+.1H NMR (400 MHz, DMSO-d6) 6 11.67 (s, 1H), 7.92 - 7.89 (m, 1H), 7.73 - 7.67 (m, 3H), 7.56 - 7.47 (m, 2H), 7.34 - 7.20 (m, 5H), 4.30 (d, J = 108.3 Hz, 1H), 4.03 (d, J= 108.3 Hz, 1H). Example 34: N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide

[0658]

[0659] The title compound was obtained in analogy to Example 23 as a white solid (6.1% yield) using 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid and tert-butyl 2-tosylhydrazine-l-carboxylate. LCMS (ESI) [M + H]+: 438.25. ’H NMR (400 MHz, DMSO-d6) 6 11.33 (s, 1H), 7.63 (dd, J= 10.3, 8.6 Hz, 3H), 7.49 (dd, J= 9.0, 5.0 Hz, 1H), 7.36 (s, 1H), 7.36 - 7.28 (m, 3H), 7.25 (dt, J = 6.2, 1.6 Hz, 3H), 3.31 (s, 2H), 2.39 (s, 3H), 2.26 (d, J = 2.3 Hz, 3H).

[0660] Example 35: N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-(difluoromethyl)benzenesulfonamide

[0661]

[0662] a) 1 -(benzylsulfanyl)-4-(difluoromethyl)benzene

[0663] To a mixture of l-bromo-4-(difluoromethyl)benzene (1 g, 4.830 mmol, 1.0 equivalent), Pd2(dba)3 (0.88 g, 0.966 mmol, 0.2 equivalent), xantphos (1.12 g, 1.932 mmol, 0.4 equivalent) and DIPEA (1.87 g, 14.490 mmol, 3.0 equivalent) in toluene (10 mL) was added phenylmethanethiol (0.90 g, 7.245 mmol, 1.5 equivalent) under nitrogen atmosphere. The reaction mixture was warmed to 100 °C and stirred for 1 h. After completion, the reaction mixture was cooled to room temperature and the organic solvent was removed under reduced pressure to obtain the residue. The residue was purified by column chromatography on silica gel eluted (PE / EA 9:1) to afford l-(benzylsulfanyl)-4-(difhioromethyl)benzene (1 g, 82.70 % yield) as a yellow oil. b) 4-(difluoromethyl)benzenesulfonyl chloride

[0664] To a mixture of l-(benzylsulfanyl)-4-(difluoromethyl)benzene (100 mg, 0.4 mmol, 1.0 equivalent) and NCS (80.02 mg, 0.6 mmol, 1.5 equivalent) in AcOH (10 mL) and H2O (2.5 mL) at room temperature. The reaction mixture was stirred for 2 h and monitored by TLC analysis. After completion, the reaction mixture was quenched with saturated aqueous NaHCO3(5 mL) and extracted with DCM (3 x 15 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure to afford 4-(difluoromethyl)benzene sulfonyl chloride (78 mg, 86.15% yield) as yellow oil without further purification.

[0665] c) N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-(difluoromethyl)benzenesulfonamide

[0666] The title compound was obtained in analogy to Example 23 as a white solid (23.8% yield) using 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid and N'-[4-(difluoromethyl)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 474.20. ’H NMR (400 MHz, DMSO-d6) 6 11.63 (s, 1H), 7.88 (d, J= 8.2 Hz, 2H), 7.74 (d, J = 8.2 Hz, 2H), 7.62 (t, J = 9.2 Hz, 1H), 7.49 (dd, J = 9.0, 5.1 Hz, 1H), 7.37 -7.21 (m, 5H), 7.16 (s, 1H), 4.30 (s, 2H), 2.22 (d, J= 2.3 Hz, 3H).

[0667] Example 36: N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide

[0668]

[0669] The title compound was obtained in analogy to Example 6 as a white solid (24.1% yield) using 3-amino-2-benzyl-6-fluoroquinazolin-4-one and p-toluenesulfonyl chloride. LC-MS (ES, m / z): [M+l] = 424.11. ’H NMR (400 MHz, DMSO-d6) 6 11.49 (s, 1H), 7.69 (ddd, J = 19.5, 6.6, 1.9 Hz, 4H), 7.60 - 7.55 (m, 1H), 7.41 - 7.29 (m, 4H), 7.29 - 7.20 (m, 3H), 4.21 – 4.55 (m, 2H), 2.41 (s, 3H).

[0670] Example 37: N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4- (difluoromethyl)benzenesulfonamide

[0671]

[0672] The title compound was obtained in analogy to Example 6 as a white solid (24.8% yield) using 3-amino-2-benzyl-6-fluoroquinazolin-4-one and 4-(difluoromethyl)benzenesulfonyl chloride. LC-MS (ES, m / z): [M+l] = 460.09. ’H NMR (400 MHz, DMSO-d6) 8 11.79 (s, 1H), 7.90 (d, J= 8.1 Hz, 2H), 7.70 (dd, J= 12.0, 7.2 Hz, 4H), 7.57 - 7.50 (m, 1H), 7.36 -7.20 (m, 5H), 7.15 (s, 1H), 4.31 (s, 2H).

[0673] Example 38: N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-ethynyl-benzenesulfonamide

[0674]

[0675] The title compound was obtained in analogy to Example 23 as a white solid (82.8% yield) using 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid and N'-(4-ethynylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 448.00.1H NMR (400 MHz, DMSO-d6) 6 11.59 (s, 1H), 7.77 - 7.70 (m, 2H), 7.64 (dd, J= 8.9, 3.7 Hz, 3H), 7.50 (dd, J= 9.0, 5.1 Hz, 1H), 7.33 (dd, J= 8.1, 6.8 Hz, 2H), 7.26 (d, J= 7.5 Hz, 3H), 4.53 (s, 1H), 3.32 (s, 2H), 2.27 (d, J = 2.3 Hz, 3H).

[0676] Example 39: N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-ethyl-benzenesulfonamide

[0677]

[0678] The title compound was obtained in analogy to Example 6 as a white solid (34.9% yield) using 3-amino-2-benzyl-6-fluoroquinazolin-4-one and 4-ethylbenzenesulfonyl chloride. LC-MS: (ES, m / z): [M+l] = 438.12 [M+H]+. ’H NMR (400 MHz, DMSO-d6) 6 11.47 (s, 1H), 7.75 - 7.65 (m, 4H), 7.59 - 7.52 (m, 1H), 7.44 - 7.37 (m, 2H), 7.36 - 7.27 (m, 2H), 7.27 - 7.19 (m, 3H), 4.22 (d, J= 141.2 Hz, 2H), 2.76 - 2.65 (m, 2H), 1.24- 1.16 (m, 3H) Example 40: N-[8-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-5-(difluoromethyl)thiophene-2-sulfonamide

[0679]

[0680] F

[0681] The title compound was obtained in analogy to Example 23 as a white solid (39.4% yield) using 3-chloro-2-(2-methoxy-2-phenylacetamido)benzoic acid and N'-[5-(difluoromethyl)thiophen-2-ylsulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 512.05. ’H NMR (400 MHz, DMSO-d6) 8 12.08 (s, 1H), 8.06 (d, J = 7.8 Hz, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.70 (dd, J = 3.9, 2.0 Hz, 1H), 7.58 - 7.53 (m, 2H), 7.50 - 7.25 (m, 6H), 5.85 (s, 1H), 3.50 - 3.35 (m, 3H).

[0682] Example 41: N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide

[0683]

[0684] The title compound was obtained in analogy to Example 23 as a white solid (64.7% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-[4-(trifluoromethyl)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 544.05.1H NMR (400 MHz, DMSO-d6) 6 11.92 (s, 1H), 8.10 - 7.86 (m, 5H), 7.46 (dd, J = 8.6, 5.6 Hz, 3H), 7.23 (dd, J = 10.1, 7.7 Hz, 2H), 5.88 (s, 1H), 3.40 (s, 3H).

[0685] Example 42: N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0686]

[0687] The title compound was obtained in analogy to Example 6 as a white solid (26.3% yield) using 3-amino-2-[methoxy(phenyl)methyl]-8-methylquinazolin-4-one and p-toluene sulfonyl chloride. MS (ESIpos): m / z = 450.00 [M+H]+.1H NMR (400 MHz, Acetonitrile-d3) 68.55 (s, 1H), 7.68 (dd, J= 8.4, 2.1 Hz, 4H), 7.48 - 7.30 (m, 8H), 5.84 (s, 1H), 3.44 (s, 3H), 2.54 (d, J= 31.7 Hz, 3H), 2.42 (s, 3H).

[0688] Example 43: 4-(l,l-difluoroethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-8-methyl- 4-oxo-quinazolin-3-yl]benzenesulfonamide

[0689]

[0690] The title compound was obtained in analogy to Example 23 as a white solid (60.7% yield) using 5-fluoro-2-(2-methoxy-2-phenylacetamido)-3-methylbenzoic acid and A'-[4-(trifluoromethyl)benzenesulfonyl]tert-butoxycarbohydrazide. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 518.15. ’H NMR (400 MHz, Acetonitrile-d3) 67.91 - 7.86 (m, 2H), 7.70 - 7.65 (m, 2H), 7.49 - 7.42 (m, 3H), 7.39 - 7.29 (m, 4H), 5.86 (s, 1H), 3.45 (s, 3H), 2.56 (s, 3H), 1.98 (d, 7= 18.7 Hz, 3H).

[0691] Example 44: 5-chloro-N-[8-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide

[0692]

[0693] The title compound was obtained in analogy to Example 23 as a white solid (34.9% yield) using 3-chloro-2-(2-methoxy-2-phenylacetamido)benzoic acid and A'-(5-chlorothiophen-2-ylsulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 496.05.!H NMR (400 MHz, DMSO-d6) 8 11.98 (s, 1H), 8.06 (s, 1H), 7.92 (d, 7= 8.0 Hz, 1H), 7.58 - 7.50 (m, 2H), 7.38 (d, J = 10.8 Hz, 5H), 7.26 (d, 7= 4.1 Hz, 1H), 5.88 (s, 1H), 3.43 (s, 3H).

[0694] Example 45: N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0695]

[0696] The title compound was obtained in analogy to Example 23 as a white solid (39.2% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and M-(4-mcthylbcnzcncsulfonyl) / e / 7-butoxycarbohydrazidc. LCMS (ESI) [M + H]+: 472.05.1H NMR (400 MHz, DMSO-d6) 6 11.39 (s, 1H), 7.91 (s, 1H), 7.77 (s, 1H), 7.72 - 7.66 (m, 2H), 7.61 (dd, 7= 8.5, 2.9 Hz, 1H), 7.40 (d, 7= 8.1 Hz, 4H), 7.20 (t, 7= 8.4 Hz, 2H), 5.80 (s, 1H), 3.36 (s, 3H), 2.42 (s, 3H). Example 46: N-[6-fluoro-2-[fluoro(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0697]

[0698] The title compound was obtained in analogy to Example 23 as a white solid (26.0% yield) using 5-fluoro-2-(2-fluoro-2-phenylacetamido)benzoic acid and A'-(4-mcthylbcnzcncsulfonyl) / e / 7-butoxycarbohydrazidc. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 442.10. ’H NMR (400 MHz, Acetonitrile-d3) 68.68 (s, 1H), 7.81 (dd, J= 9.2, 4.8 Hz, 1H), 7.68 - 7.60 (m, 3H), 7.54 - 7.48 (m, 3H), 7.43 (dd, J= 5.1, 1.9 Hz, 3H), 7.33 (d, J = 8.1 Hz, 2H), 6.94 (d, J = 45.9 Hz, 1H), 2.43 (s, 3H).

[0699] Example 47: N-(2-benzyl-8-methyl-4-oxo-quinazolin-3-yl)-3-fluoro-benzenesulfonamide

[0700]

[0701] The title compound was obtained in analogy to Example 6 as a white solid (17.9% yield) using 3-amino-2-benzyl-8-methylquinazolin-4-one and 3-fluorobenzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H] +: 424.1. ’H NMR (400 MHz, DMSO-d6) 5 11.61 (s, 1H), 7.65 (q, J= 7.0, 6.1 Hz, 1H), 7.58 (ddt, J= 10.4, 7.7, 1.5 Hz, 4H), 7.45 (d, J= 8.1 Hz, 1H), 7.38 - 7.30 (m, 2H), 7.26 (dd, J= 9.4, 7.3 Hz, 4H), 4.48 (s, 1H), 4.10 (s, 1H), 2.36 (s, 3H).

[0702] Example 48: N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0703]

[0704] The title compound was obtained in analogy to Example 6 as a white solid (18.5% yield) using 3-amino-6-fluoro-2-(methoxy (phenyl) methyl) quinazolin-4 (3H)-one and 4-methylbenzenesulfonyl chloride. LC-MS: (ES, m / z): [M+l] = 454.05.1H NMR (400 MHz, Acetonitrile-d3) 67.75 (s, 1H), 7.72 - 7.64 (m, 2H), 7.60 (td, J= 8.7, 3.0 Hz, 1H), 7.52 (dd, J = 8.5, 3.0 Hz, 1H), 7.44 - 7.37 (m, 2H), 7.37 - 7.29 (m, 5H), 5.82 (s, 1H), 3.41 (s, 3H), 2.43 (s, 3H).

[0705] Example 49: 4-(difluoromethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0706]

[0707] The title compound was obtained in analogy to Example 23 as a white solid (29.0% yield) using 3-fluoro-6-(2-methoxy-2-phenylacetamido)-2-methylbenzoic acid and / V'-[4-(difluoromcthyl)bcnzcncsulfonyl| / e / 7-butoxycarbohydrazidc. LCMS (ESI) [M + H]+: 504.10. ’H NMR (400 MHz, DMSO-d6) 3 11.60 (s, 1H), 7.91 (d, J= 8.1 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H), 7.69 (s, 2H), 7.36 (dd, J= 23.7, 14.4 Hz, 5H), 7.18 (s, 1H), 5.91 (s, 1H), 3.41 (s, 3H), 2.21 (s, 3H).

[0708] Example 50: N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0709]

[0710] The title compound was obtained in analogy to Example 6 as a white solid (39.3% yield) using 3-amino-5-chloro-2-(methoxy(phenyl)methyl)quinazolin-4(3H)-one and p- toluene sulfonyl chloride. LC-MS: (ES, m / z): [M+l] =470.1H NMR (300 MHz, DMSO-d6) 5 11.31 (s, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.86 (dd, J = 8.0, 1.4 Hz, 1H), 7.76 -7.66 (m, 2H), 7.50 (t, J= 7.9 Hz, 2H), 7.39 (q, J= 7.6, 6.8 Hz, 6H), 5.87 (s, 1H), 3.39 (s, 3H), 2.43 (s, 3H).

[0711] Example 51: N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4- (difluoromethyl)benzenesulfonamide

[0712]

[0713] a) 5 -chloro-2-(methoxy(phenyl)methyl)-4H-benzo [d] [ 1,3] oxazin-4-one

[0714] A solution of 2-amino-6-chlorobenzoic acid (2.0 g, 11.6 mmol, 1 equiv) and 2-methoxy-2- phenylacetic acid (2.3 g, 13.9 mmol, 1.2 equiv) in ACN (30 mL) was treated with TCFH (3.9 g, 13.9 mmol, 1.2 equiv) and NMI (2.9 g, 34.9 mmol, 3 equiv). The resulting mixture was stirred for additional 1 h at room temperature. The reaction was quenched with water (10 mL) at 0 °C. The resulting mixture was extracted with EtOAc (2 x 20 mL). Dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 10 % to 50 % gradient in 10 min; detector, UV 254 nm. This resulted in 5- chloro-2-(methoxy(phenyl)methyl)-477-benzo[t / ][l,3]oxazin-4-one (1.5 g, 42.6% yield) as a white solid. LC-MS: (ES, m / z): [M+l] =302.

[0715] b) 3-amino-5-chloro-2-(methoxy(phenyl)methyl)quinazolin-4(3H)-one A solution of 5-chloro-2-(methoxy(phenyl)methyl)-477-benzo[t / ][l,3]oxazin-4-one (1.5 g, 4.9 mmol, 1 equiv) in EtOH (10 mL) was treated with hydrazine hydrate (10 mL) at room temperature. The resulting mixture was stirred for additional 1 h at 80 °C. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 3-amino-5-chloro-2-(methoxy(phenyl)methyl)quinazolin-4(37 )-one (700.0 mg, 44.5% yield) as a white solid. LC-MS: (ES, m / z): [M+l] =316.

[0716] c) N- [5-chloro-2- [methoxy(phenyl)methyl] -4-oxo-quinazolin-3-yl] -4-(difluoromethyl)benzenesulfonamide

[0717] The title compound was obtained in analogy to Example 6 as a white solid (38.0% yield) using 3-amino-5-chloro-2-(methoxy(phenyl)methyl)quinazolin-4(3H)-one and 4-(difluoromethyl)benzene sulfonyl chloride. LC-MS: (ES, m / z): [M+l] =506.1H NMR (400 MHz, DMSO-d6) 6 11.63 (s, 1H), 7.99 (dd, J= 12.6, 8.0 Hz, 3H), 7.88 -7.74 (m, 3H), 7.56 - 7.42 (m, 3H), 7.42 - 7.34 (m, 3H), 7.06 (t, J = 55.4 Hz, 1H), 5.90 (s, 1H), 3.42 (s, 3H).

[0718] Example 52: 4-methoxy-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide

[0719] N

[0720] o=s=o o

[0721]

[0722] O.

[0723] The title compound was obtained in analogy to Example 23 as a white solid (21.2% yield) using 2-(2-methoxy-2-phenylacetamido)-6-methylbenzoic acid and A'-(4-mcthoxybcnzcncsulfonyl) / e / 7-butoxycarbohydrazidc. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 466.0.1H NMR (300 MHz, DMSO-d6) δ 10.94 (s, 1H), 7.75 - 7.60 (m, 4H), 7.43 (d, J= 7.0 Hz, 2H), 7.36 (d, J = 7.5 Hz, 3H), 7.31 - 7.22 (m, 1H), 7.13 - 7.02 (m, 2H), 5.94 (s, 1H), 3.85 (s, 3H), 3.15 (s, 3H), 2.42 (s, 3H).

[0724] Example 53: 4-(dimethylamino)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0725]

[0726] The title compound was obtained in analogy to Example 6 as a white solid (17.6% yield) using 3-amino-6-fluoro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 4-(dimethylamino)benzenesulfonyl chloride. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 483.05. ’H NMR (400 MHz, Acetonitrile-d3) 58.35 (s, 1H), 7.75 (s, 1H), 7.59 (t, J= 7.2 Hz, 1H), 7.52 (dd, J= 9.1, 2.5 Hz, 3H), 7.45 -7.34 (m, 2H), 7.34 (d, J= 6.7 Hz, 3H), 6.70 - 6.62 (m, 2H), 5.89 (s, 1H), 3.42 (s, 3H), 3.01 (s, 6H).

[0727] Example 54: N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0728]

[0729] The title compound was obtained in analogy to Example 23 as a white solid (54.36% yield) using 3,5-difluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and 4 A'-(4-mcthylbcnzcncsulfonyl) / e / 7-butoxycarbohydrazidc. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 472.05. ’H NMR (400 MHz, Acetonitrile-d3) 68.60 (s, 1H), 7.71 - 7.66 (m, 2H), 7.51 - 7.45 (m, 1H), 7.43 - 7.31 (m, 8H), 5.82 (s, 1H), 3.41 (s, 3H), 2.43 (s, 3H).

[0730] Example 55: N- [6-fluoro-2- [methoxy(phenyl)methyl] -5-methyl-4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0731]

[0732] The title compound was obtained in analogy to Example 23 as a white solid (58.8% yield) using 3-fluoro-6-(2-methoxy-2-phenylacetamido)-2-methylbenzoic acid and N'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LC-MS: (ES, m / z): [M+l] = 468.13. ’H NMR (400 MHz, DMSO-d6) 6 11.28 (s, 1H), 7.66 (dd, J = 22.6, 7.8 Hz, 4H), 7.41 -7.30 (m, 7H), 5.86 (s, 1H), 3.38 (s, 3H), 2.40 (s, 3H), 2.30 - 2.22 (m, 3H).

[0733] Example 56: N-[6-fluoro-2-[(3-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0734]

[0735] The title compound was obtained in analogy to Example 23 as a white solid (16.5% yield) using 5-fluoro-2-[2-(3-fluorophenyl)-2-methoxyacetamido]benzoic acid and / V'-(4-mcthylbcnzcncsulfonyl) / e / 7-butoxycarbohydrazidc. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 472.00. ’H NMR (400 MHz, Methanol-d4) 67.92 (dd, J= 9.3, 4.8 Hz, 1H), 7.67 (t, J = 10.2 Hz, 3H), 7.49 (d, J = 7.7 Hz, 1H), 7.35 (t, J = 10.3 Hz, 4H), 7.29 (d, J = 7.7 Hz, 1H), 7.20 (d, J= 9.8 Hz, 1H), 7.06 (t, J = 8.8 Hz, 1H), 6.05 (s, 1H), 3.53 (s, 3H), 2.44 (s, 3H).

[0736] Example 57: N-[5-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0737] F

[0738]

[0739] The title compound was obtained in analogy to Example 23 as a white solid (25.8% yield) using 2-chloro-6-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and / V'-(4-mcthylbcnzcncsulfonyl) / e / 7-butoxycarbohydrazidc. LCMS (ESI): m / z = 488.08 [M + H]+. ‘H NMR (400 MHz, DMSO-d6) δ 11.26 (s, 1H), 7.81 - 7.74 (m, 1H), 7.65 (d, J= 8.0 Hz, 2H), 7.56 (dd, J= 7.6, 1.4 Hz, 1H), 7.38 (d, J = 8.3 Hz, 4H), 7.20 (d, J = 8.7 Hz, 2H), 5.76 (s, 1H), 3.33 (s, 3H), 2.40 (s, 3H).

[0740] Example 58: N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]-4- methoxy-benzenesulfonamide

[0741]

[0742] The title compound was obtained in analogy to Example 23 as a white solid (18.6% yield) using 5-fluoro-2-[2-(4-fluorophenyl)acetamido]benzoic acid and N'-(4-methoxybenzenesulfonyl)tert-butoxycarbohydrazide. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 458.00. ’H NMR (300 MHz, DMSO-d6) 5 11.14 (s, 1H), 7.69 (ddd, J= 10.7, 6.8, 2.0 Hz, 4H), 7.56 (dt, J= 8.5, 1.8 Hz, 1H), 7.27 (dd, J= 8.6, 5.5 Hz, 2H), 7.10 (s, 1H), 7.17 - 7.02 (m, 3H), 4.55 (s, 2H) 3.85 (s, 3H).

[0743] Example 59: 3-fluoro-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo- quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0744]

[0745] The title compound was obtained in analogy to Example 23 as a white solid (28.6% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-(3-fluoro-4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI): m / z = 490.10 [M + H]+. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (s, 2H), 7.62 (dd, J = 8.5, 2.8 Hz, 1H), 7.57 - 7.52 (m, 1H), 7.52 - 7.48 (m, 2H), 7.45 (t, J = 7.2 Hz, 2H), 7.21 (t, J = 8.7 Hz, 2H), 5.89 (s, 1H), 3.38 (s, 3H), 2.34 (d, J = 1.9 Hz, 3H). Example 60: N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[0746]

[0747] The title compound was obtained in analogy to Example 23 as a white solid (40.1% yield) using 3-chloro-5-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and A'-(4-mcthylbcnzcncsulfonyl) / e / 7-butoxycarbohydrazidc. LCMS (ESI) [M + H]+: 487.95.!H NMR (400 MHz, Acetonitrile-d3) 67.77 (dd, J= 8.5, 2.9 Hz, 1H), 7.70 - 7.66 (m, 2H), 7.48 (dd, 7= 8.1, 2.9 Hz, 1H), 7.44 - 7.40 (m, 2H), 7.37 - 7.32 (m, 5H), 5.84 (s, 1H), 3.42 (s, 3H), 2.43 (s, 3H).

[0748] Example 61: N-(6-fluoro-2-(methoxy(phenyl)methyl)-8-methyl-4-oxoquinazolin- 3(4H)-yl)-4-methylbenzenesulfonamide

[0749]

[0750] The title compound was obtained in analogy to Example 23 as a white solid (33.1% yield) using 5-fluoro-2-(2-methoxy-2-phenylacetamido)-3-methylbenzoic acid and 4-toluenesulfonyl hydrazide. LCMS (ESI) [M + H]+: 468.00.1H NMR (400 MHz, Acetonitrile-d3) 38.58 (s, 1H), 7.71 - 7.63 (m, 2H), 7.45 (d, 7= 21.3 Hz, 3H), 7.33 (dd, 7 = 8.2, 3.9 Hz, 6H), 5.83 (s, 1H), 3.43 (s, 3H), 2.43 (s, 3H), 2.15 (s, 3H).

[0751] Example 62: N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methoxybenzenesulfonamide

[0752]

[0753] The title compound was obtained in analogy to Example 23 as a white solid (24.9% yield) using 5-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and A'-(4-methoxybenzenesulfonyl)tert-butoxycarbohydrazide. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 470.15. ’H NMR (300 MHz, DMSO-d6) 6 11.08 (s, 1H), 7.80 - 7.67 (m, 4H), 7.59 (dd, J = 8.4, 3.0 Hz, 1H), 7.46 - 7.29 (m, 5H), 7.14 - 7.05 (m, 2H), 5.90 (s, 1H), 3.88 (s, 3H), 3.05 (s, 3H).

[0754] Example 63: N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin- 3(4H)-yl)-4-(l-fluorocyclopropyl)benzenesulfonamide

[0755]

[0756] a) 4-(l-fluorocyclopropyl)benzenesulfonyl chloride

[0757] To a stirred mixture of l-(benzylsulfanyl)-4-(l-fluorocyclopropyl)benzene (200 mg, 0.774 mmol, 1 equiv) and water (2 mL) in AcOH (8 mL) were added N-Chloro succinimide (310.1 mg, 2.322 mmol, 3.00 equiv) in portions at 0 °C. The resulting mixture was stirred at room temperature for 30 min. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (12:1) to afford 4-(l-fluorocyclopropyl)benzenesulfonyl chloride (160 mg, 88.1% yield) as a white liquid.

[0758] b) A'-[4-( l-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide

[0759] To a stirred mixture of 4-(l-fluorocyclopropyl)benzenesulfonyl chloride (350 mg, 1.49 mmol, 1 equiv) and tert-butyl carbamate (262.0 mg, 2.236 mmol, 1.50 equiv) in MeCN (10 mL) were added pyridine (176.9 mg, 2.236 mmol, 1.50 equiv) dropwise at 0 °C. The resulting mixture was stirred at room temperature for 1 h. The resulting mixture was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 10% to 50% gradient in 20 min, UV 254 nm to afford N'-[4-(1-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide (290 mg, 58.86% yield) as a white solid. LCMS (ESI) [M - H]+: 329.10

[0760] c) N-(6-fhioro-2-((4-fhiorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(l-fluorocyclopropyl)benzenesulfonamide

[0761] The title compound was obtained in analogy to Example 23 as a white solid (76.1% yield) using 5-fhioro-2-[2-(4-fhiorophenyl)-2-methoxyacetamido]benzoic acid and A'-[4-(l-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 516.25. ’H NMR (400 MHz, Acetonitrile-d3) 68.73 (s, 1H), 7.81 - 7.70 (m, 3H), 7.63 - 7.57 (m, 1H), 7.51 (dd, J= 8.5, 3.0 Hz, 1H), 7.47 - 7.42 (m, 2H), 7.38 -7.32 (m, 2H), 7.14 - 7.04 (m, 2H), 5.86 (s, 1H), 3.43 (s, 3H), 1.66 - 1.56 (m, 2H), 1.27 -1.18 (m, 2H).

[0762] Example 64: N-(6-fluoro-2-((2-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[0763]

[0764] The title compound was obtained in analogy to Example 23 as a white solid (28.2% yield) using 5-fhioro-2-[2-(2-fhiorophenyl)-2-methoxyacetamido]benzoic acid and N'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LC-MS (ES, m / z): [M+l] =472. H-NMR-PH-ICA-PBh-TS -O-l^H NMR (300 MHz, DMSO-d6) 5 11.19 (s, 1H), 7.91 -7.61 (m, 5H), 7.51 - 7.11 (m, 6H), 6.12 (s, 1H), 3.39 (s, 3H), 2.42 (s, 3H).

[0765] Example 65: N-(2-benzyl-8-methoxy-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide

[0766]

[0767] The title compound was obtained in analogy to Example 6 as a white solid (60.0% yield) using 3-amino-2-benzyl-8-methoxyquinazolin-4-one and N'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 436.05.1H NMR (400 MHz, DMSO-d6) 5 11.40 (s, 1H), 7.68 - 7.60 (m, 2H), 7.46 - 7.26 (m, 7H), 7.26 - 7.19 (m, 3H), 4.47 (s, 1H), 4.05 (d, J= 19.5 Hz, 1H), 3.90 (s, 3H), 2.40 (s, 3H). Example 66: N-[2-[fluoro(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide

[0768]

[0769] The title compound was obtained in analogy to Example 23 as a white solid (14.7% yield) using 2-(2-fluoro-2-phenylacetamido)-6-methylbenzoic acid and N'-(5-methylthiophen-2-ylsulfonyl)tert-butoxycarbohydrazide. MS (ESIpos): m / z = 444.08 [M+H]+.1H NMR (400 MHz, Acetonitrile-d3) 68.77 (s, 1H), 7.69 (t, J= 7.8 Hz, 1H), 7.60 - 7.50 (m, 3H), 7.47 -7.39 (m, 3H), 7.34 (dd, J = 20.7, 5.6 Hz, 2H), 6.99 (d, J = 45.9 Hz, 1H), 6.80 (dd, 7= 3.9, 1.1 Hz, 1H), 2.52- 2.45 (m, 6H).

[0770] Example 67: N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide

[0771]

[0772] The title compound was obtained in analogy to Example 23 as a white solid (5.0% yield) using 2-chloro-6-(2-methoxy-2-phenylacetamido)benzoic acid and A7-(5-methylthiophen-2-ylsulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 499.10. ’H NMR (400 MHz, DMSO-d6) 8 10.82 (s, 1H), 7.83 - 7.64 (m, 2H), 7.57 - 7.44 (m, 3H), 7.42 - 7.30 (m, 5H), 6.72 (d, J= 9.0 Hz, 2H), 5.82 (s, 1H), 3.34 (s, 3H), 3.00 (s, 6H).

[0773] Example 68: N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide

[0774]

[0775] The title compound was obtained in analogy to Example 23 as a white solid (12.5% yield) using 5-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and 2V-(5-methylthiophen-2-ylsulfonyl)tert-butoxycarbohydrazide. LCMS (ESI): m / z = 460.08 [M + H]+.1H NMR (400 MHz, DMSO-d6) 6 11.60 (s, 1H), 7.95 - 7.63 (m, 3H), 7.47 (d, J= 3.8 Hz, 1H), 7.43 - 7.23 (m, 5H), 6.92 (d, J = 3.8 Hz, 1H), 5.80 (s, 1H), 3.36 (s, 3H), 2.53 (s, 3H).

[0776] Example 69: N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide

[0777]

[0778] The title compound was obtained in analogy to Example 23 as a white solid (11.7% yield) using 3,5-difluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and A'-[4-(dimethylamino)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 501. ‘HNMR (400 MHz, DMSO-d6) 5 11.02 - 10.71 (m, 1H), 7.91 - 7.71 (m, 1H), 7.61 - 7.50 (m, 3H), 7.36 - 7.50 (m, 5H), 6.73 (d, J= 8.7 Hz, 2H), 5.83 (s, 1H), 3.01 (s, 6H), 3.40 -3.30 (m, 3H).

[0779] Example 70: 4-(dimethylamino)-N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0780]

[0781] The title compound was obtained in analogy to Example 6 as a white solid (35.0% yield) using 3-amino-2-[methoxy(phenyl)methyl]-8-methylquinazolin-4-one and 4-(dimethylamino)benzenesulfonyl chloride. MS (ESIpos): m / z = 479.00 [M+H]+.1H NMR (400 MHz, Acetonitrile-d3) 68.40 (s, 1H), 7.69 (d, J= 8.0 Hz, 2H), 7.54 - 7.32 (m, 8H), 6.69 - 6.61 (m, 2H), 5.91 (s, 1H), 3.44 (s, 3H), 3.00 (s, 6H), 2.74 - 2.50 (m, 3H).

[0782] Example 71: N- [6-chloro-2- [(4-fluorophenyl)-methoxy-methyl] -4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide

[0783]

[0784] The title compound was obtained in analogy to Example 23 as a white solid (18.6% yield) using 5-chloro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-[4-(dimethylamino)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 517.

[0785] 1H NMR (400 MHz, DMSO-d6) 5 11.50 - 10.90 (s, 1H), 7.95 - 7.80 (m, 3H), 7.52 - 7.30 (m, 4H), 7.19 (d, J= 9.3 Hz, 2H), 6.73 (d, J = 8.6 Hz, 2H), 6.01 - 5.70 (m, 1H), 5.82 (s, 3H), 3.01 (s, 6H).

[0786] Example 72: 4-(difluoromethyl)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4- oxo-quinazolin-3-yl]benzenesulfonamide

[0787]

[0788] The title compound was obtained in analogy to Example 23 as a white solid (67.4% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-[4-(difluoromethyl)benzenesulfonyl]tert-butoxycarbohydrazide. LC-MS (ES, m / z): LCMS (ESI) [M + H]+: 508.10. ’H NMR (400 MHz, Acetonitrile-d3) 68.83 (s, 1H), 7.94 - 7.89 (m, 2H), 7.80 - 7.67 (m, 3H), 7.63 - 7.57 (m, 1H), 7.51 - 7.42 (m, 3H), 7.14 - 7.06 (m, 2H), 6.89 (t, J = 55.5 Hz, 1H), 5.88 (s, 1H), 3.44 (s, 3H).

[0789] Example 73: N-[5-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3- yl]-4-(dimethylamino)benzenesulfonamide

[0790]

[0791] The title compound was obtained in analogy to Example 23 as a white solid (21.7% yield) using 2-chloro-6-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and / V-[4- (difluoromethyl)benzenesulfonyl]tert-butoxycarbohydrazide. MS (ESIpos): m / z = 517.10 [M+H]+.1H NMR (400 MHz, DMSO-d6) 8 10.80 (s, 1H), 7.76 (s, 2H), 7.58 - 7.45 (m, 3H), 7.44 - 7.14 (m, 4H), 6.72 (d, J = 8.7 Hz, 2H), 5.82 (s, 1H), 3.35 (s, 3H).

[0792] Example 74: 4-(dimethylamino)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4- oxo-quinazolin-3-yl]benzenesulfonamide

[0793]

[0794] The title compound was obtained in analogy to Example 23 as a white solid (5.7% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and 7V'-[4-(dimethylamino)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 501.1H NMR (400 MHz, DMSO-d6) 8 11.6 - 10.8 (m, 1H), 7.89 (s, 1H), 7.75 (s, 1H), 7.64-7.58 (m, 1H), 7.51 (d, J= 8.6 Hz, 2H), 7.41 (s, 2H), 7.18 (s, 2H), 6.73 (d, J= 8.7 Hz, 2H), 6.10 - 5.50 (m, 1H), 3.30 (s, 3H), 3.01 (s, 6H).

[0795] Example 75: N-[2-[(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0796]

[0797] The title compound was obtained in analogy to Example 23 as a white solid (38.0% yield) using 2-[2-(4-fluorophenyl)-2-methoxyacetamido]-3-methoxybenzoic acid and 7V'-[4-(dimethylamino)benzenesulfonyl]tert-butoxycarbohydrazide. LC-MS (ESI, m / z): [M+ H]+: 484.1. ’H NMR (400 MHz, DMSO-d6) 6 11.30 (s, 1H), 7.66 (d, J = 7.9 H

[0798]

[0799] z, 3H), 7.45 -7.16 (m, 8H), 5.78 (s, 1H), 3.97 - 3.80 (m, 3H), 3.35 (s, 3H), 2.40 (s, 3H).

[0800] Example 76: N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0801]

[0802] The title compound was obtained in analogy to Example 23 as a white solid (20.7% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido] benzoic acid and A'-[4-(dimethylamino)benzenesulfonyl]tert-butoxycarbohydrazide. LC-MS (ESI, m / z): [M+ H]+: 490.1.1H NMR (400 MHz, DMSO-76) < M 1.46 (s, 1H), 7.93 (s, 1H), 7.69 (d, J= 8.1 Hz, 2H), 7.48 (d, J = 8.3 Hz, 1H), 7.39 (d, J = 8.0 Hz, 4H), 7.20 (d, J = 8.4 Hz, 2H), 5.78 (s, 1H), 3.346(s, 3H), 2.41 (s, 3H).

[0803] Example 77: 4-(l,l-difluoroethyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[0804]

[0805] F

[0806] The title compound was the first peak from the chiral separation of 4-(l,l-difluoroethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide (Example 43) using conditions A (33% yield, RT=7.05min, first peak) as a white solid. LCMS(ECI) [M + H]+: 518.2. ’H NMR (400 MHz, DMSO-d6) 8 11.67 (s, 1H), 7.91 (d, J= 8.2 Hz, 2H), 7.77 (d, 7= 8.3 Hz, 2H), 7.67 (s, 1H), 7.43 - 7.34 (m, 6H), 5.84 (s, 1H), 2.63 (s, 3H), 2.28 (s, 2H), 2.05 (s, 1H), 2.01 (s, 2H), 1.96 (s, 1H).

[0807] Example 78: N-[6-fluoro-2-[methoxy-(4-methoxyphenyl)methyl]-4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0808]

[0809] The title compound was obtained in analogy to Example 23 as a white solid (11.7% yield) using 5-fluoro-2-[2-methoxy-2-(4-methoxyphenyl) acetamido] benzoic acid and 7V'-[4-(dimethylamino)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 484.1. ’H NMR (400 MHz, DMSO-d6) 3 11.37 (s, 1H), 7.90 (s, 1H), 7.77 (s, 2H), 7.67 (d, J= 8.0 Hz, 1H), 7.59 (d, J= 8.5 Hz, 1H), 7.39 (d, J= 7.9 Hz, 2H), 7.28 (d, J= 8.4 Hz, 2H), 6.90 (d, J= 8.1 Hz, 2H), 5.71 (s, 1H), 3.72 (s, 3H), 3.32 (s, 3H) 2.41 (s, 3H).

[0810] Example 79: N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide

[0811]

[0812] The title compound was obtained in analogy to Example 23 as a light yellow solid (57.9% yield) using 3,5-difluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and 7V'-[4-(l-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. MS (ESIpos): m / z = 516.00 [M+H] +. ’H NMR (400 MHz, DMSO-d6) 6 11.63 (s, 1H), 7.93 (s, 1H), 7.80 (d, J = 8.5 Hz, 2H), 7.49 (d, J= 7.9 Hz, 1H), 7.45 - 7.30 (m, 7H), 5.83 (s, 1H), 3.36 (s, 3H), 1.68 - 1.56 (m, 2H), 1.32 - 1.23 (m, 2H).

[0813] Example 80: N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0814]

[0815] a) N-{8-[(benzyloxy)methyl]-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide

[0816] The title compound was obtained in analogy to Example 23 as a white solid (73.0% yield) using 3-[(benzyloxy)methyl]-2-(2-methoxy-2-phenylacetamido) benzoic acid and A'-(4-me thy Ibenzene sulfonyl) tert-butoxycarbohydrazide. LCMS (ESI) [M + H] +: 556.1. b) N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide.

[0817] A solution of A-{8-[(benzyloxy)methyl]-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (200 mg, 0.360 mmol, 1 equiv) in MeOH (3 mL) was treated with triehtylamine (0.3 mL) and Pd / C (199.9 mg, 1.879 mmol) at 0 °C. The mixture was stirred overnight at room temperature under th. The residue was purified by reverse phase flash chromatography [Mobile Phase A: Water (0.3% NH4HCO3), Mobile Phase B: acetonitrile; Gradient: 0% B to 70% B in 30 min] to give N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide (30 mg, 17.76% yield) as a white solid. LCMS (ESI) [M + H]+: 466.1. ’H NMR (400 MHz, DMSO-d6) 5 11.34 (s, 1H), 7.91 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.70 - 7.64 (m, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.37 (d, J = 8.4 Hz, 7H), 5.84 (s, 1H), 5.30 (s, 1H), 5.03 (s, 2H), 3.36 (s, 3H), 2.40 (s, 3H).

[0818] Example 81: N-[8-(fluoromethyl)-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0819] 9r-

[0820] 0=^=0 o

[0821]

[0822] A solution of N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (Example 80, 40 mg, 0.086 mmol, 1 equiv) in DCM (1.5 mL) was treated with DAST (27.7 mg, 0.172 mmol, 2 equiv) at -78 °C under nitrogen atmosphere. The mixture was stirred for 2 hours at -78 °C. The reaction was quenched with H2O at 0 °C. The resulting mixture was extracted with EA (3 x 5 mL). The combined organic layers were washed with H2O (1 x 5 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reverse phase flash chromatography [Mobile Phase A: Water (0.3% FA), Mobile Phase B: acetonitrile; Gradient: 0% B to 70% B in 30 min] to give N-[8-(fhioromethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (3.6 mg, 8.71% yield) as a white solid. LCMS (ESI) [M + H] +: 468.1. ’H NMR (400 MHz, DMSO-d6) 5 11.90 - 11.40 (s, 1H), δ 7.90 (d, J = 8.5 Hz, 2H), 7.67 (d, J = 7.3 Hz, 2H), 7.54 (s, 1H), 7.42 (s, 3H), 7.35 (s, 4H), 5.89 (s, 3H), 3.35 (s, 3H), 2.40 (s, 3H).

[0823] Example 82: N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl] quinoline-6-sulfonamide

[0824]

[0825] The title compound was obtained in analogy to Example 23 as a white solid (22.0% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido] benzoic acid and N'-(quinoline-6-sulfonyl) tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 509.2.1H NMR (400 MHz, DMSO-d6) <5 11.76 (s, 1H), 9.09 (dd, J= 4.2, 1.8 Hz, 1H), 8.58 (d, J = 8.2 Hz, 1H), 8.53 (s, 1H), 8.23 (d, J = 9.0 Hz, 1H), 8.12 (dd, J= 8.9, 2.2 Hz, 1H), 7.91 (d, 7= 5.7 Hz, 1H), 7.77 (s, 1H), 7.68 (dd, 7= 8.3, 4.2 Hz, 1H), 7.51 - 7.41 (m, 3H), 7.22 (t, 7= 8.8 Hz, 2H), 5.87 (s, 1H), 3.38 (s, 3H).

[0826] Example 83: N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-isopropenyl-benzenesulfonamide F

[0827]

[0828] The title compound was obtained in analogy to Example 23 as a white solid (10.4% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-[4-(2-hydroxypropan-2-yl)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 498.15. ’H NMR (400 MHz, DMSO-d6) 6 11.50 (s, 1H), 7.90 (s, 1H), 7.79 - 7.67 (m, 4H), 7.73 (s, 1H), 7.60 (dd, J= 8.4, 2.8 Hz, 1H), 7.43 (dd, J = 8.4, 5.5 Hz, 2H), 7.21 (t, J= 8.6 Hz, 2H), 5.83 (s, 1H), 5.62 (s, 1H), 5.30 (t, J= 1.5 Hz, 1H), 3.35 (s, 3H), 2.15 (s, 3H).

[0829] Example 84: 4-(l-fluorocyclopropyl)-N-[8-methoxy-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0830]

[0831] The title compound was obtained in analogy to Example 23 as a white solid (51.0% yield) using 3-methoxy-2-(2-methoxy-2-phenylacetamido)benzoic acid and N'-[4-(2-hydroxypropan-2-yl)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 510.20. ’H NMR (400 MHz, Acetonitrile-d3) 68.67 (s, 1H), 7.85 - 7.72 (m, 2H), 7.46 -7.24 (m, 10H), 5.86 (s, 1H), 3.96 (s, 3H), 3.42 (s, 3H), 1.64 - 1.54 (m, 2H), 1.25 - 1.15 (m, 2H).

[0832] Example 85: N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide

[0833]

[0834] The title compound was obtained in analogy to Example 23 as a white solid (44.5% yield) using 2-chloro-6-(2-methoxy-2-phenylacetamido)benzoic acid and A'-[4-(l-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. MS (ESIpos): m / z = 514.00 [M+H] +. ’H NMR (400 MHz, Acetonitrile-d3) δ 8.68 (s, 1H), 7.78 - 7.74 (m, 2H), 7.70 (s, 2H), 7.48 - 7.42 (m, 3H), 7.33 (dd, J = 10.8, 4.2 Hz, 5H), 5.91 (s, 1H), 3.46 (s, 3H), 1.65 - 1.55 (m, 2H), 1.24- 1.14 (m, 2H).

[0835] Example 86: N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide

[0836]

[0837] The title compound was obtained in analogy to Example 23 as a white solid (54.9% yield) using 3-chloro-5-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and A'-[4-(l-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. MS (ESIpos): m / z = 532.00 [M+H] +. ’H NMR (400 MHz, Acetonitrile-d3) 67.82 - 7.75 (m, 3H), 7.51 - 7.30 (m, 8H), 5.85 (s, 1H), 3.44 (s, 3H), 1.65 - 1.57 (m, 2H), 1.23 (dd, J= 9.0, 6.3 Hz, 2H). Example 87: (R)-4-(3,3-difluoroazetidin-l-yl)-N-(6-fluoro-2- (methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0838]

[0839] a) (7?)-(acetyloxy)(phenyl)acetic acid

[0840] A solution of (R)-mandelic acid (10.00 g, 65.75 mmol, 1.00 equiv) in DCM (100 mL) was treated with AcCl (10.30 g, 131.45 mmol, 2.00 equiv) at 0 °C for 1 min under nitrogen atmosphere followed by the addition of pyridine (10.40 g, 131.45 mmol, 2.00 equiv) drop wise at 0 °C. The resulting mixture was stirred at room temperature for 2 hours under nitrogen atmosphere. The reaction was quenched by the addition of water (10 mL) at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by re versed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 17% to 25% gradient in 20 min; UV 254 nm to afford (7?)-(acetyloxy)( phenyl )acetic acid (8.03 g, 62.93% yield) as a white solid. LCMS(ESI) [M - H]-: 193.00.

[0841] b) ( l / ?)-2-chloro-2-oxo- 1 -phenylethyl acetate

[0842] To a stirred solution of (7?)-(acetyloxy)(phenyl)acetic acid (8.00 g, 41.19 mmol, 1.00 equiv) in DCM (80 mL) was added SOCl2 (9.80 g, 82.39 mmol, 2.00 equiv) and DMF (150.57 mg, 2.06 mmol, 0.05 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 hour under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to afford crude ( l / ?)-2-chloro-2-oxo- 1 -phenylethyl acetate (8.30 g, 91.53% yield) as a yellow oil. The crude product was used in the next step directly without further purification.

[0843] c) (R)- [(2-carbamoyl-4-fluorophenyl)carbamoyl] (phenyl)methyl acetate

[0844] To a stirred solution of ( l / ?)-2-chloro-2-oxo- 1 -phenylethyl acetate (8.30 g, 39.03 mmol, 1.00 equiv) in DCM (20 mL) was added 2-amino-5-fluorobenzamide (6.02 g, 39.05 mmol, 1.00 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 3 hours under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford (R)-[(2-carbamoyl-4-fluorophenyl)carbamoyl](phenyl)methyl acetate (7.3 g, 56.62% yield) as a yellow solid. LCMS(ESI) [M - H]-: 329.05.

[0845] d) 6-fluoro-2-[(R)-hydroxy(phenyl)methyl]-3H-quinazolin-4-one

[0846] A solution of (R)-[(2-carbamoyl-4-fluorophenyl)carbamoyl](phenyl)methyl acetate (7.00 g, 21.19 mmol, 1.00 equiv) in EtOH (30 mL) was treated with NaOH (3.39 g, 84.76 mmol, 4.00 equiv) under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 hour under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (1:1) to afford 6-fluoro-2-[(R)-hydroxy(phenyl)methyl]-3H-quinazolin-4-one (5.00 g, 87.41% yield) as a white solid. LCMS (ESI) [M + H]+: 271.00.

[0847] e) 3-amino-6-fluoro-2-[(R)-hydroxy(phenyl)methyl]quinazolin-4-one

[0848] A solution of 6-fluoro-2-[(R)-hydroxy(phenyl)methyl]-3H-quinazolin-4-one (4.00 g, 14.80 mmol, 1.00 equiv) in THF (200 mL) was treated with t-BuOK (1.66 g, 14.80 mmol, 1.00 equiv) at 0 °C. The mixture was stirred 40 min at 0 °C, then amino diphenylphosphinate (5.18 g, 22.20 mmol, 1.50 equiv) was added at 0 °C. The mixture was stirred 60 min at room temperature. The resulting mixture was filtered the filter cake was washed with EA (3 x 15 mL). The filtrate was concentrated under reduced pressure. The residue was purified by reverse phase separation column [Mobile Phase A: Water (0.3% FA), Mobile Phase B: acetonitrile; Gradient: 20% B to 70% B in 30 min] to give 3-amino-6-fluoro-2-[(R)-hydroxy(phenyl)methyl]quinazolin-4-one (3.60 g, 85.26% yield) as a light yellow solid. LCMS (ESI) [M + H]+: 286.00.

[0849] f) 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one

[0850] A solution of 3-amino-6-fluoro-2-[(R)-hydroxy(phenyl)methyl]quinazolin-4-one (3.40 g, 11.91 mmol, 1.00 equiv) in THF (200 mL) was treated with t-BuOK (5.35 g, 47.67 mmol, 4.00 equiv) at 0 °C. The mixture was stirred 30 min at 0 °C, then methyl trifluoromethane sulfonate (5.87 g, 35.75 mmol, 3.00 equiv) was added at 0 °C. The mixture was stirred 60 min at room temperature. The resulting mixture was filtered, the filter cake was washed with EA (3 x 30 mL). The filtrate was concentrated under reduced pressure. The residue was purified by reverse phase separation column [Mobile Phase A: Water (0.3% FA), Mobile Phase B: acetonitrile; Gradient: 20% B to 80% B in 30 min] to give 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one (2.60 g, 73.03% yield) as a brown oil. LCMS (ESI) [M + H]+: 300.00.

[0851] g) N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide To a stirred solution of 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one (2.00 g, 6.68 mmol, 1.00 equiv) and 4-iodobenzenesulfonyl chloride (2.42 mg, 80.20 mmol, 1.20 equiv) in THF (20 mL) was added LiHMDS (13.40 mL, 13.36 mmol, 2.00 equiv) in portions at -78 °C under nitrogen atmosphere. The resulting mixture was stirred at -78 °C for 1 hour under nitrogen atmosphere. The reaction was quenched with water at room temperature. The resulting mixture was extracted with EtOAc (2 x 80 mL). The combined organic layers were washed with brine (2 x 40 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (4:1) to afford N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide (1.5 g, 39.71% yield) as a white solid. LCMS (ESI) [M + H]+: 566.00.

[0852] h) (R)-4-(3,3-difluoroazetidin-1-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0853] A solution of N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide (80 mg, 0.142 mmol, 1 equiv), 3,3-difluoroazetidine hydrochloride (36.7 mg, 0.284 mmol, 2 equiv), Cs2CO3(92.2 mg, 0.284 mmol, 2 equiv), Pd2(dba)3 (25.9 mg, 0.028 mmol, 0.2 equiv) and XPhos (27.0 mg, 0.057 mmol, 0.4 equiv) in dioxane (4 mL) was stirred at 100 °C for 4 h under nitrogen atmosphere. Desired product could be detected by LCMS. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Prep C18 OBD Column, 30*150 mm, 5m; Mobile Phase A: Water (0.1% FA), Mobile Phase B: ACN; Flow rate: 60mL / min; Gradient: 42% B to 62% B in 9 min; Wave Length: 254nm / 220nm; RTl(min): 9.52) to afford 4-(3,3-difluoroazetidin-1-yl)-N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}benzenesulfonamide (46.1 mg, 61.41% yield, 99.6% purity) as a white solid. LCMS (ESI) [M + H]+: 531.05. ’H NMR (400 MHz, Acetonitrile-d3) δ 8.50 (s, 1H), 7.73 (s, 1H), 7.62 - 7.55 (m, 3H), 7.52 (dd, J = 8.5, 3.0 Hz, 1H), 7.44 - 7.40 (m, 2H), 7.38 - 7.29 (m, 3H), 6.54 - 6.47 (m, 2H), 5.90 (s, 1H), 4.40 - 4.30 (m, 4H), 3.43 (s, 3H).

[0854] Example 88: (R)-4-(4,4-difluoropiperidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0855]

[0856] The title compound was obtained in analogy to Example 87 as a white solid (41.2% yield) using N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide and 4,4-difluoropiperidine. LCMS (ESI) [M + H]+: 559.10. ’H NMR (400 MHz, Acetonitrile-d3) 58.40 (s, 1H), 7.73 (s, 1H), 7.62 - 7.55 (m, 3H), 7.51 (dd, J = 8.5, 3.0 Hz, 1H), 7.44 - 7.39 (m, 2H), 7.38 - 7.29 (m, 3H), 6.99 - 6.91 (m, 2H), 5.90 (s, 1H), 3.54 (d, J= 11.6 Hz, 4H), 3.43 (s, 3H), 2.08 - 1.98 (m, 4H).

[0857] Example 89: (R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-morpholinobenzenesulfonamide

[0858]

[0859] The title compound was obtained in analogy to Example 87 as a white solid (45.4% yield) using N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide and morpholine. LCMS (ESI) [M- H]’: 523.05.1H NMR (400 MHz, Acetonitrile-d3) 68.46 (s, 1H), 7.74 (s, 1H), 7.62 - 7.55 (m, 3H), 7.52 (dd, J= 8.4, 3.0 Hz, 1H), 7.44 - 7.38 (m, 2H), 7.34 (d, J = 6.8 Hz, 3H), 6.92 - 6.84 (m, 2H), 5.88 (s, 1H), 3.76 (t, J= 4.9 Hz, 4H), 3.42 (s, 3H), 3.28 (t, J= 4.9 Hz, 4H).

[0860] Example 90: 4-(2,2-difluorocyclopropyl)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)- 4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0861]

[0862] The title compound was obtained in analogy to Example 87 as a white solid (15.0% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluorocyclopropyl)benzenesulfonyl chloride. LC-MS: (ES, m / z): [M+l] = 516. ’H NMR (400 MHz, Acetonitrile-d3) 68.82 - 8.22 (m, 1H), 7.75 (d, J = 8.3 Hz, 3H), 7.60 (td, J = 8.7, 3.0 Hz, 1H), 7.48 (dt, J= 8.5, 3.2 Hz, 1H), 7.43 - 7.25 (m, 7H), 5.83 (d, J= 2.2 Hz, 1H), 3.42 (d, J= 1.7 Hz, 3H), 2.99 (td, J = 12.4, 8.3 Hz, 1H), 2.06-1.97 (m, 1H), 1.86 (m, 1H).

[0863] Example 91: (R)-4-(2,2-difluoroethoxy)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0864]

[0865] The title compound was obtained in analogy to Example 87 as a white solid (12.2% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluoroethoxy) benzene sulfonyl chloride. LC-MS (ESI, m / z): [M - H]: 518.10.!H NMR (400 MHz, DMSO-d6) 6 11.57 (d, J= 143.8 Hz, 1H), 7.97 - 7.52 (m, 5H), 7.48 - 7.27 (m, 5H), 7.22 - 7.12 (m, 2H), 6.59 - 6.25 (m, 1H), 5.86 (s, 1H), 4.50 - 4.36 (m, 2H), 3.38 (s, 3H).

[0866] Example 92: (R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((l-fluorocyclopropyl)methoxy)benzenesulfonamide

[0867]

[0868] The title compound was obtained in analogy to Example 87 as a white solid (15.0% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluorocyclopropyl)benzenesulfonyl chloride. LC-MS: (ES, m / z): [M+l] = 528. ’H NMR (400 MHz, Acetonitrile-d3) 68.39 (s, 1H), 7.82 - 7.67 (m, 3H), 7.59 (td, J = 8.7, 3.0 Hz, 1H), 7.52 (dd, J = 8.5, 3.0 Hz, 1H), 7.46 - 7.39 (m, 2H), 7.39 - 7.29 (m, 3H), 7.06 - 6.98 (m, 2H), 5.89 (s, 1H), 4.45 - 4.10 (m, 2H), 3.44 (s, 3H), 1.23 - 1.10 (m, 2H), 0.92 - 0.82 (m, 2H).

[0869] Example 93: N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(l-fluoro-2-methylpropyl)benzenesulfonamide

[0870]

[0871] The title compound was obtained in analogy to Example 87 as a white solid (15.0% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(l-fluoro-2-methylpropyl)benzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H] +: 514.10. ’H NMR (400 MHz, DMSO-d6) 5 11.71 (d, J = 134.6 Hz, 1H), 7.81 (d, J = 8.1 Hz, 4H), 7.63 - 7.44 (m, 3H), 7.36 (s, 5H), 5.87 (s, 1H), 5.57 - 5.31 (m, 1H), 3.38 (s, 3H), 2.23 - 1.99 (m, 1H), 1.12- 0.58 (m, 6H).

[0872] Example 94: (R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[0873]

[0874] The title compound was the second peak from the chiral separation of N-[6,8-difluoro-2-[methoxy(phenyl)methyl] -4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide (Example 54) using conditions B (35.2% yield, RT=15.36min, second peak) as a white solid. LCMS (ESI) [M + H]+: 472.15. ’H NMR (400 MHz, DMSO-d6) 6 11.50 (s, 1H), 7.92 (s, 1H), 7.69 (d, J= 8.1 Hz, 2H), 7.51 - 7.31 (m, 8H), 5.81 (s, 1H), 3.36 (s, 3H), 2.41 (s, 3H).

[0875] Example 95: (R)-4-(3-(difluoromethyl)azetidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0876]

[0877] The title compound was obtained in analogy to Example 87 as a white solid (20.4% yield) using N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide and 3-(difluoromethyl)azetidine. LCMS (ESI) [M+ H]+: 545.10. ’H NMR (400 MHz, Acetonitrile-d3) 68.38 (s, 1H), 7.75 (s, 1H), 7.62 - 7.50 (m, 4H), 7.45 - 7.27 (m, 5H), 6.44 - 6.37 (m, 2H), 6.31 - 6.02 (m, 1H), 5.89 (s, 1H), 4.11 - 4.04 (m, 2H), 3.97 - 3.91 (m, 2H), 3.42 (s, 3H), 3.28 - 3.21 (m, 1H).

[0878] Example 96: (R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(3-methoxyazetidin-l-yl)benzenesulfonamide

[0879]

[0880] The title compound was obtained in analogy to Example 87 as a white solid (29.9% yield) using N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide and 3-methoxyazetidine hydrochloride. LCMS (ESI) [M + H]+: 525.10.!H NMR (400 MHz, Acetonitrile-d3) 68.42 (s, 1H), 7.78 (s, 1H), 7.59 (s, 1H), 7.55 - 7.48 (m, 3H), 7.37 (d, J= 27.5 Hz, 5H), 6.42 - 6.31 (m, 2H), 5.88 (s, 1H), 4.37 - 4.30 (m, 1H), 4.17 - 4.09 (m, 2H), 3.81 - 3.73 (m, 2H), 3.42 (s, 3H), 3.30 (s, 3H).

[0881] Example 97: 4-(2,2-difluoroethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[0882]

[0883] The title compound was obtained in analogy to Example 87 as a white solid (1.8% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluoroethyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 504.05.1H NMR (400 MHz, DMSO-d6) 5 11.52 (s, 1H), 7.79 (s, 1H), 7.77 (d, J= 8.3 Hz, 3H), 7.59 - 7.54 (m, 3H), 7.36 (d, J= 15.0 Hz, 5H), 6.15 - 6.54 (m, 1H), 6.79 (s, 1H), 3.36 - 3.39 (m, 1H), 3.35 (s, 3H), 3.27-3.29 (m, 1H).

[0884] Example 98: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(3-methoxypyrrolidin-l-yl)benzenesulfonamide

[0885]

[0886] The title compound was obtained in analogy to Example 87 as a white solid (42.6% yield) using N- { 6-fluoro-2- [ ( / ?)-mcthoxy( phenyl )methyl ]-4-oxoquinazol i n-3-yl } -4-iodobenzene sulfonamide and 3-methoxypyrrolidine. LCMS (ESI): [M-H]': 537.10.!H NMR (400 MHz, Acetonitrile-d3) 68.28 (s, 1H), 7.74 (s, 1H), 7.62 - 7.55 (m, 1H), 7.54 - 7.50 (m, 3H), 7.43 - 7.39 (m, 2H), 7.34 (d, J = 6.7 Hz, 3H), 6.55 - 6.49 (m, 2H), 5.90 (s, 1H), 4.13 - 4.08 (m, 1H), 3.49 - 3.44 (m, 1H), 3.42 (s, 3H), 3.38 (t, J= 4.3 Hz, 3H), 3.31 (s, 3H), 2.14- 2.04 (m, 2H).

[0887] Example 99: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-[methyl(tetrahydrofuran-3-yl)amino]benzenesulfonamide

[0888]

[0889] The title compound was obtained in analogy to Example 87 as a white solid (35.6% yield) using N- { 6-fluoro-2- [ ( / ?)-mcthoxy( phenyl )methyl ]-4-oxoquinazol i n-3-yl } -4-iodobenzene sulfonamide and A-methyloxolan-3-amine. LCMS (ESI): [M-H]': 537.05. ’H NMR (400 MHz, DMSO-d6) 5 10.98 (s, 1H), 7.90 (s, 1H), 7.77 (s, 1H), 7.59 (d, J= 8.5 Hz, 1H), 7.54 - 7.48 (m, 2H), 7.41 - 7.29 (m, 5H), 6.88 (d, J = 8.9 Hz, 2H), 5.83 (s, 1H), 4.66 (s, 1H), 4.00 - 3.92 (m, 1H), 3.81 - 3.70 (m, 2H), 3.66 - 3.58 (m, 1H), 3.33 (s, 3H), 2.87 (s, 3H), 2.33 - 2.21 (m, 1H), 1.81 (s, 1H).

[0890] Example 100: 4-(2,2-difluorocyclobutyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[0891]

[0892] The title compound was obtained in analogy to Example 87 as a white solid (6.8% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluorocyclobutyl)benzenesulfonyl chloride. LCMS (ESI): [M+H]+: 530.19.!H NMR (400 MHz, DMSO-d6) 6 11.49 (s, 1H), 7.90 (s, 1H), 7.79 (d, J= 8.2 Hz, 3H), 7.56 (d, J = 8.3 Hz, 1H), 7.47 (d, J = 8.1 Hz, 2H), 7.36 (s, 5H), 5.79 (s, 1H), 4.33 - 4.17 (m, 1H), 3.33 (s, 3H), 2.75 - 2.54 (m, 2H), 2.27 - 2.18 (m, 1H), 2.15 - 2.01 (m, 1H).

[0893] Example 101: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-[3- (methoxymethyl)azetidin- 1 -yl] benzenesulfonamide

[0894]

[0895] I

[0896] The title compound was obtained in analogy to Example 87 as a white solid (30.2% yield) using N- { 6-fluoro-2- [ ( R)-methoxy( phenyl )methyl ]-4-oxoquinazol i n-3-yl } -4-iodobenzene sulfonamide and 3 -(methoxymethyl) azetidine. LCMS (ESI): [M-H]': 537.10. ’H NMR (400 MHz, DMSO-d6) 6 10.97 (s, 1H), 7.90 (s, 1H), 7.78 (d, J= 9.1 Hz, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.53 - 7.46 (m, 2H), 7.43 - 7.25 (m, 5H), 6.41 (d, J = 8.6 Hz, 2H), 5.87 (d, J = 30.7 Hz, 1H), 4.03 - 3.96 (m, 2H), 3.67 (d, J= 6.3 Hz, 2H), 3.53 (d, J= 6.3 Hz, 2H), 3.34 (s, 3H), 3.29 (s, 3H), 3.02 - 2.92 (m, 1H).

[0897] Example 102: N-[8-cyclopropyl-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[0898]

[0899] The title compound was obtained in analogy to Example 87 as a white solid (30.1% yield) using 3-cyclopropyl-5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and 2V-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI): [M+H]+: 512.15. ’H NMR (400 MHz, Acetonitrile-d3) 69.01 - 8.23 (m, 1H), 7.73 - 7.64 (m, 2H), 7.47 (dd, J= 8.4, 5.5 Hz, 2H), 7.34 (d, J= 8.1 Hz, 2H), 7.27 -7.21 (m, 1H), 7.10 (t, J = 8.9 Hz, 2H), 7.02 (dd, J= 10.2, 2.9 Hz, 1H), 5.87 (s, 1H), 3.43 (s, 3H), 2.85 (s, 1H), 2.45 (s, 3H), 1.22 - 1.04 (m, 2H), 0.98 - 0.77 (m, 2H).

[0900] Example 103: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(oxetan-2-yl)benzenesulfonamide

[0901]

[0902] A solution of N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide (110 mg, 0.195 mmol, 1 equiv), oxetane-2-carboxylic acid (39.73 mg, 0.390 mmol, 2 equiv), Cs2CO3(126.79 mg, 0.390 mmol, 2 equiv), Dtbpy (7.83 mg, 0.029 mmol, 0.15 equiv), Ir[dF(CF3)ppy]2(dtbpy))PF6 (2.18 mg, 0.002 mmol, 0.01 equiv) and 1,2-dimethoxyethane; dichloronickel (4.28 mg, 0.020 mmol, 0.1 equiv) in DMF (4 mL) was irritated under 450 nm blue LEDs in photoreactor at room temperature for 24 h under nitrogen atmosphere. Desired product could be detected by LCMS. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH C18 OBD Column 30*150mm 5pm; Mobile Phase A: Water(0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 10% B to 10% B in 1.5 min, 10% B to 38% B in 2 min, 38% to 54% in 12 min; Wave Length: 254nm / 220nm; RT1(min): 11.42) to afford N- {6-fluoro-2-[(R)- methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl } -4-(oxetan-2-yl)benzenesulfonamide (19.8 mg, 20.54% yield, 95.1% purity) as a white solid. LCMS (ESI): [M+H]+: 496.10.!H NMR (400 MHz, Acetonitrile-^) 57.83 - 7.77 (m, 2H), 7.76 - 7.70 (m, 1H), 7.62 - 7.46 (m, 4H), 7.44 - 7.28 (m, 5H), 5.89 - 5.79 (m, 2H), 4.81 - 4.74 (m, 1H), 4.64 - 4.57 (m, 1H), 3.42 (d, J = 0.9 Hz, 3H), 3.13 - 3.04 (m, 1H), 2.57 - 2.48 (m, 1H).

[0903] Example 104: N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide

[0904]

[0905] a) A-{6,8-difluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide

[0906] The title compound was obtained in analogy to Example 159 as a white solid (99.3% yield) using 3-amino-6,8-difhioro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-iodobenzene-1- sulfonyl chloride.

[0907] b) N-[6,8-difluoro-4-oxo-2-[-(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide

[0908] A solution of A-{6,8-difhioro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide (365.00 mg, 0.62 mmol, 1.00 equiv) in dioxane (5 mL) was added morpholine (81.77 mg, 0.93 mmol, 1.50 equiv), Pd2(dba)3 (28.65 mg, 0.03 mmol, 0.05 equiv) and X-Phos (29.83 mg, 0.06 mmol, 0.10 equiv) followed by the addition of Cs2CO3(407.73 mg, 1.25 mmol, 2.00 equiv) in portions at room temperature. The resulting mixture was stirred at 100 °C for 2 hours under nitrogen atmosphere. The residue was purified by HPLC with the following conditions (Column: Xselect CSH C18 OBD Column 30*150mm 5pm, n; Mobile Phase A: Water(0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 5% B to 5% B in 1.5 min, 5% B to 41% B in 2 min, 41% to 58% in 15 min; Wave Length: 254nm / 220nm; RT1(min): 12.72) to afford N-[6,8-difhioro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide (61.7 mg, 18.17% yield) as a white solid. LCMS (ESI) [M+H]+: 543.05. ’H NMR (400 MHz, DMSO-d6) 8 11.17 (s, 1H), 7.91 (s, 1H), 7.61 - 7.35 (m, J = 12.3 Hz, 8H), 7.06 - 6.98 (m, 2H), 5.84 (s, 1H), 3.77 - 3.70 (m, 4H), 3.32 (t, J = 10.3 Hz, 3H), 3.2 (t, J= 10.3 Hz, 4H).

[0909] Example 105: N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide

[0910]

[0911] The title compound was obtained in analogy to Example 6 as a white solid (14.5% yield) using 3-amino-2-benzyl-6-fluoroquinazolin-4-one and 4-fluorobenzenesulfonyl chloride. LCMS (ESI): [M+H]+: 428.05. ’H NMR (400 MHz, DMSO-d6) 6 11.67 (s, 1H), 7.90 -7.81 (m, 2H), 7.76 - 7.69 (m, 2H), 7.57 (dt, J= 8.3, 1.7 Hz, 1H), 7.42 (t, J= 8.8 Hz, 2H), 7.33 (dd, J= 9.0, 6.0 Hz, 2H), 7.27 (d, J= 7.2 Hz, 3H), 4.49 (s, 1H), 4.12 (s, 1H).

[0912] Example 106: N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-2- (trifluoromethyl)benzenesulfonamide

[0913]

[0914] The title compound was obtained in analogy to Example 6 as a white solid (15.5% yield) using 3-amino-2-benzyl-6-fluoroquinazolin-4-one and 2-(trifluoromethyl)benzenesulfonyl chloride. LCMS (ESI): [M+H]+: 478.05. ’H NMR (400 MHz, DMSO-d6) 6 11.54 (s, 1H), 8.14 - 8.07 (d, J = 7.8 Hz, 1H), 8.04 - 7.98 (d, J = 7.7 Hz, 1H), 7.94 - 7.89 (t, J = 7.6 Hz, 1H), 7.88 - 7.81 (t, J= 7.6 Hz, 1H), 7.77 - 7.68 (m, 2H), 7.60 - 7.53 (m, 1H), 7.36 - 7.21 (m, 5H), 4.34 (m, 2H).

[0915] Example 107: N- [2- [(4-chlorophenyl)methyl] -6-fluoro-4-oxo-quinazolin-3-yl] -2-(trifluoromethyl)benzenesulfonamide Cl

[0916]

[0917] The title compound was obtained in analogy to Example 6 as a light yellowish solid (10.4% yield) using 3-amino-2-[(4-chlorophenyl)methyl]-6-fluoroquinazolin-4-one and 2-(trifluoromethyl)benzenesulfonyl chloride. LCMS (ESI): [M+H]+: 511.95.!H NMR (400 MHz, DMSO-d6) 6 11.49 (s, 1H), 8.10 (d, J = 7.9 Hz, 1H), 8.01 (dd, J = 7.8, 1.4 Hz, 1H), 7.94 - 7.82 (m 2H), 7.74 - 7.69 (m, 2H), 7.58 - 7.54 (m, 1H), 7.41 - 7.36 (m, 2H), 7.26 (d, J = 8.1 Hz, 2H), 4.25 (s, 2H).

[0918] Example 108: N-[6-chloro-2-(m-tolylmethyl)-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide

[0919] F3C

[0920]

[0921] The title compound was obtained in analogy to Example 1 (10.7% yield) using 5-chloro-2-(2-(m-tolyl)acetamido)benzoic acid and 2-(trifluoromethyl)benzenesulfonohydrazide. LCMS (ESI) [M+H]+: 508.0. ’H NMR (300 MHz, DMSO-d6) 5 11.55 (s, 1H), 8.11 (d, J = 7.6 Hz, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.97 - 7.76 (m, 4H), 7.66 (d, J = 8.5 Hz, 1H), 7.29 -7.14 (m, 1H), 7.05 (d, J = 14.0 Hz, 3H), 4.32 - 4.15 (m, 2H), 2.27 (s, 3H).

[0922] Example 109: N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2- (trifluoromethyl)benzenesulfonamide

[0923]

[0924] The title compound was obtained in analogy to Example 1 (15.5% yield) using 2-methyl-6-(2-phenylacetamido)benzoic acid and 2- (trifluoromethyl)benzene sulfonohydrazide. LCMS (ESI) [M+H]+: 474.0. ’H NMR (300 MHz, DMSO-d6) 5 11.32 (s, 1H), 8.15 - 7.97 (m, 2H), 7.97 - 7.75 (m, 3H), 7.70 - 7.60 (m, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.37 - 7.14 (m, 6H), 4.41 (d, J = 15.0 Hz, 1H), 4.04 (d, J = 15.2 Hz, 1H), 2.34 (s, 3H).

[0925] Example 110: N-[7-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide

[0926]

[0927] The title compound was obtained in analogy to Example 1 (6.9% yield) using 4-chloro-2-(2-methoxy-2-phenylacetamido)benzoic acid and 4-isopropylbenzenesulfonohydrazide. LCMS (ESI) [M+H]+: 498.0. ’H NMR (300 MHz, DMSO-d6) 5 11.73 - 11.29 (m, 1H), 7.95 - 7.80 (m, 2H), 7.79 - 7.67 (m, 2H), 7.58 (d, J = 8.6, 2.0 Hz, 1H), 7.47 (d, J = 8.2 Hz, 2H), 7.36 (s, 5H), 5.76 (s, 1H), 3.33 (s, 3H), 3.14 - 2.90 (m, 1H), 1.23 (d, J = 6.9 Hz, 6H).

[0928] Example 111: 4-isopropyl-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0929]

[0930] The title compound was obtained in analogy to Example 1 (14.9% yield) using 2-(2-methoxy-2-phenylacetamido)-6-methylbenzoic acid and 4-isopropylbenzenesulfonohydrazide. LCMS (ESI) [M+H]+: 478.1. ’H NMR (300 MHz, DMSO-d6) 5 11.66 - 10.90 (m, 1H), 7.79 - 7.54 (m, 4H), 7.54 - 7.18 (m, 8H), 5.90 (s, 1H), 3.39 (s, 3H), 3.07 - 2.90 (m, 1H), 2.32 (s, 3H), 1.21 (d, J = 6.9 Hz, 6H). Example 112: N-(2-benzyl-6-chloro-4-oxo-quinazolin-3-yl)-2- (trifluoromethyl)benzenesulfonamide

[0931]

[0932] The title compound was obtained in analogy to Example 6 (3.5% yield) as a white solid using 2-benzyl-6-chloro-477-quinazolin-3-amine and 2- (trifluoromethyl) benzenesulfonyl chloride. LCMS (ESI): [M+H]+: 494.10. ’H NMR (400 MHz, DMSO-d6) 6 11.57 (s, 1H), 8.16 - 8.07 (m, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.90 - 7.77 (m, 4H), 7.64 (d, J = 8.7 Hz, 1H), 7.37 - 7.29 (m, 2H), 7.26 (d, J= 7.1 Hz, 3H), 4.25 (s, 2H).

[0933] Example 113: N-[2-[(4-chlorophenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide

[0934] ci

[0935]

[0936] The title compound was obtained in analogy to Example 1 (1.8% yield) using 2-(2-(4-chlorophenyl)acetamido)-6-methylbenzoic acid and 2-(trifluoromethyl)benzenesulfonohydrazide. LCMS (ESI) [M+H]+: 508.1. ’H NMR (300 MHz, DMSO-d6) 5 11.27 (s, 1H), 8.13 - 7.95 (m, 2H), 7.95 - 7.75 (m, 2H), 7.72 - 7.54 (m, 1H), 7.47 - 7.33 (m, 3H), 7.33 - 7.17 (m, 3H), 4.33 (s, 2H), 2.34 (s, 3H).

[0937] Example 114: N-[5-methyl-2-(m-tolylmethyl)-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide

[0938]

[0939] The title compound was obtained in analogy to Example 1 (1.0% yield) iusing 2-methyl-6-(2-(m-tolyl)acetamido)benzoic acid and 2-(trifluoromethyl)benzenesulfonohydrazide. LCMS (ESI) [M+H]+: 488.3. ‘H NMR (300 MHz, DMSO-d6) 5 11.41 -11.21 (m, 1H), 5 8.18 -7.95 (m, 3H), 7.27-7.11 (m, 3H), 7.11-6.96(m, 4H), 6.56-6.46 (m, 1H), 4.32-4.15 (m, 2H),2.72 (s, 3H), 2.27 (s, 3H).

[0940] Example 115: N- [4- [(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)sulfamoyl] -3-(trifluoromethyl)phenyl]acetamide

[0941]

[0942] a) A-(2-benzyl-6-fluoro-4-oxoquinazolin-3-yl)-4-bromo-2- (trifluoromethyl)benzenesulfonamide

[0943] The title compound was obtained in analogy to Example 6 (42.4% yield) as a white solid using 3-amino-2-benzyl-6-fluoroquinazolin-4-one and 4-bromo-2-(trifluoromethyl)benzenesulfonyl chloride.

[0944] b) N-[4-[(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)sulfamoyl]-3-(trifluoromethyl)phenyl] acetamide

[0945] 2V-(2-benzyl-6-fluoro-4-oxoquinazolin-3-yl)-4-bromo-2-(trifluoromethyl)benzenesulfonamide (170 mg, 0.306 mmol, 1 equiv) and acetamide (27.07 mg, 0.459 mmol, 1.5 equiv) in dioxane (4 mL) were added Pd2(dba)3 (55.96 mg, 0.061 mmol, 0.2 equiv), BrettPhos (65.61 mg, 0.122 mmol, 0.4 equiv) and K2CO3 (126.70 mg, 0.918 mmol, 3 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred for additional 2 h at 90 °C. The resulting mixture was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 15 min; detector, UV 254 nm. This resulted in N-[4-[(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)sulfamoyl]-3-(trifluoromethyl)phenyl]acetamide (41.9 mg, 25.49% yield) as a white solid. LCMS (ESI):

[0946] [M+H]+: 535.00. ’H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 10.66 (s, 1H), 8.23 (s, 1H), 8.01 (d, J= 8.9 Hz, 1H), 7.92 (d, J = 8.7 Hz, 1H), 7.70 (d, J = 6.4 Hz, 2H), 7.59 (dd, J = 8.5, 2.0 Hz, 1H), 7.36 - 7.28 (m, 2H), 7.24 (d, J= 7.5 Hz, 3H), 4.40 (s, 1H), 4.07 (s, 1H), 2.13 (s, 3H).

[0947] Example 116: N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-fluoro-2-methyl-benzenesulfonamide

[0948]

[0949] F

[0950] The title compound was obtained in analogy to Example 6 as a white solid (5.7% yield) using 3-amino-2-benzyl-6-fluoroquinazolin-4-one and 4-fluoro-2-methylbenzenesulfonyl chloride. LCMS (ESI): [M+H]+: 442.00. ’H NMR (400 MHz, DMSO-d6) 6 11.56 (s, 1H), 7.75 - 7.68 (m, 3H), 7.60 - 7.55 (m, 1H), 7.39 - 7.33 (m, 1H), 7.33 - 7.30 (m, 2H), 7.29 -7.24 (m, 1H), 7.24 - 7.18 (m, 2H), 7.13 - 7.06 (m, 1H), 4.42 - 4.01 (m, 2H), 2.67 (s, 3H).

[0951] Example 117: N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,6-dichloro-benzenesulfonamide

[0952]

[0953] The title compound was obtained in analogy to Example 6 as a white solid (20.2% yield) using 3-amino-2-benzyl-5-methylquinazolin-4-one and 2,6-dichlorobenzenesulfonyl chloride. LCMS (ESI): [M+H]+: 474.05. ’H NMR (400 MHz, DMSO-d6) 3 11.62 (s, 1H), - Ill - 7.67 - 7.57 (m, 4H), 7.40 (d, J= 8.1 Hz, 1H), 7.35 - 7.21 (m, 6H), 4.228(s, 2H), 2.45 (s, 3H).

[0954] Example 118: N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-2-chloro-4- fluoro-benzenesulfonamide

[0955]

[0956] The title compound was obtained in analogy to Example 23 as a white solid (53.7% yield) using 3-fluoro-2-methyl-6-(2-phenylacetamido)benzoic acid and / V-(2-chloro-4- fluorobenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI): [M+H]+: 476.05. ’H NMR (300 MHz, DMSO-d6) 6 11.67 (s, 1H), 7.94 (dd, J= 9.0, 5.9 Hz, 1H), 7.78 (dt, J = 8.7, 2.4 Hz, 1H), 7.64 (tt, J = 9.3, 2.4 Hz, 1H), 7.49 (dd, J= 9.0, 5.1 Hz, 1H), 7.42 - 7.19 (m, 6H), 4.10 (s, 2H), 2.36 (d, J= 2.3 Hz, 3H).

[0957] Example 119: N-(2-benzyl-8-chloro-4-oxo-quinazolin-3-yl)-4-chloro- benzenesulfonamide

[0958]

[0959] The title compound was obtained in analogy to Example 23 as a white solid (20.3% yield) using 3-chloro-2-(2-phenylacetamido)benzoic acid and N'-(4-chlorobenzenesulfonyl)tert- butoxycarbohydrazide. LCMS (ESI): [M+H]+: 460.00.1H NMR (300 MHz, DMSO-d6) 6 11.80 (s, 1H), 8.00 (dd, J= 7.8, 1.4 Hz, 1H), 7.85 - 7.77 (m, 3H), 7.67 - 7.61 (m, 2H), 7.47 (t, J = 7.9 Hz, 1H), 7.37 - 7.24 (m, 5H), 4.43 - 4.28 (m, 2H).

[0960] Example 120: N-(2-benzyl-8-chloro-5-fluoro-4-oxo-quinazolin-3-yl)-2-chloro- benzenesulfonamide

[0961]

[0962] The title compound was obtained in analogy to Example 23 as a white solid (24.0% yield) using 3-chloro-6-fluoro-2-(2-phenylacetamido)benzoic acid and N'-(2-chlorobenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI): [M+H]+: 477.95.!H NMR (400 MHz, DMSO-d6) 6 11.70 (s, 1H), 7.99 (dd, J= 8.8, 4.8 Hz, 1H), 7.93 - 7.91 (m, 1H), 7.73 - 7.68 (m, 2H), 7.53 - 7.48 (m, 1H), 7.34 - 7.24 (m, 6H), 4.19 (s, 2H).

[0963] Example 121: 4-chloro-N-[5-chloro-2-[hydroxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide

[0964] O=s=o O Cl

[0965]

[0966] a) N-(2-{ [(tert-butyldiphenylsilyl)oxy](phenyl)methyl }-5-chloro-4-oxoquinazolin-3-yl)-4-chlorobenzenesulfonamide

[0967] The title compound was obtained in analogy to Example 23 as a light yellowish solid (45.7% yield) using 2-{2-[(tert-butyldiphenylsilyl)oxy]-2-phenylacetamido}-6-chlorobenzoic acid and N'-(4-chlorobenzenesulfonyl)tert-butoxycarbohydrazide.

[0968] b) 4-chloro-N-[5-chloro-2-[hydroxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0969] To a stirred solution of N-(2-{[(tert-butyldiphenylsilyl)oxy](phenyl)methyl}-5-chloro-4-oxoquinazolin-3-yl)-4-chlorobenzenesulfonamide (300.0 mg, 0.42 mmol, 1 equiv) in DMF (5 mL) was added triethylamine trihydrofluoride (338.3 mg, 2.10 mmol, 5 equiv) dropwise at room temperature. The resulting mixture was stirred for overnight at room temperature. The residue product was purified by reverse phase flash with the following conditions (The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 10% to 50% gradient in 10 min; detector, UV 254 nm. ) to afford 4-chloro-A-{5-chloro-2-[hydroxy(phenyl)methyl]-4-oxoquinazolin-3-yl}benzenesulfonamide (92.0 mg, 45.15% yield) as a white solid. LCMS (ESI): [M+H]+: 490.25. ’H NMR (400 MHz, DMSO-d6) 5 11.64- 11.47 (s, 1H), 7.94 - 7.67 (m, 4H), 7.63 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 7.8 Hz, 1H), 7.41 - 7.14 (m, 5H), 6.05 (d, J = 42.8 Hz, 2H).

[0970] Example 122: 2-chloro-N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide

[0971]

[0972] The title compound was obtained in analogy to Example 23 as a white solid (21.9% yield) using 2-chloro-6-(2-methoxy-2-phenylacetamido)benzoic acid and N'-(2-chlorobenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI): [M+H]+: 490.05. ’H NMR (400 MHz, DMSO-d6) d 11.57 (s, 1H), 7.91 (d, J= 7.9 Hz, 1H), 7.65 (s, 3H), 7.54 -7.40 (m, 4H), 7.33 (q, J= 8.0, 7.5 Hz, 3H), 7.12 (s, 1H), 5.78 (s, 1H), 3.22 (s, 3H).

[0973] Example 123: 4-(l,l-difluoroethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0974]

[0975] The title compound was obtained in analogy to Example 6 as a white solid (54.1% yield) using 3-amino-6-fhioro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 4-( 1, 1-difhioroethyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 504.15. ’H NMR (400 MHz, Acetonitrile-d3) 68.70 (s, 1H), 7.89 (d, J= 8.6 Hz, 2H), 7.74 (d, J= 6.1 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.63 - 7.57 (m, 1H), 7.50 - 7.47 (m, 1H), 7.43 - 7.42 (m, 2H), 7.39 - 7.32 (m, 3H), 5.86 (s, 1H), 3.44 (s, 3H), 1.99 (d, J= 18.8 Hz, 3H). Example 124: 5-bromo-N-[6-fluoro-2-[fluoro(phenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide

[0976] O=s=o o

[0977]

[0978] The title compound was obtained in analogy to Example 23 as a white solid (51.1% yield) using 5-fluoro-2-(2-fluoro-2-phenylacetamido)benzoic acid and N'-(5-bromothiophen-2-ylsulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 511.90. ’H NMR (400 MHz, Acetonitrile-d3) 69.00 (s, 1H), 7.82 (s, 1H), 7.68 - 7.60 (m, 2H), 7.56 - 7.50 (m, 2H), 7.47 - 7.42 (m, 3H), 7.38 (d, J= 4.1 Hz, 1H), 7.17 (d, J= 4.1 Hz, 1H), 6.96 (d, J = 45.8 Hz, 1H).

[0979] Example 125: N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylpyridine-2-sulfonamide

[0980]

[0981] The title compound was obtained in analogy to Example 156 as a white solid (8.4% yield) using 3-amino-6-fluoro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 5-methylpyridine-2-sulfonyl chloride. LCMS (ESI): [M+H]+: 455.11. ’H NMR (400 MHz, DMSO-d6) 511.68 (s, 1H), 8.56 (s, 1H), 7.98 -7.80 (m, 3H), 7.76 (s, 1H), 7.62 (dd, J = 8.4, 2.8 Hz, 1H), 7.38 (dd, J = 22.8, 8.3 Hz, 5H), 5.94 (s, 1H), 3.30 (s, 3H), 2.44 (s, 3H).

[0982] Example 126: 4-(difluoromethoxy)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0983]

[0984] The title compound was obtained in analogy to Example 23 as a white solid (42.0% yield) using 5-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and N'-[4-(difluoromethoxy)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI): [M+H]+: 506.20. ’H NMR (300 MHz, DMSO-d6) 6 11.35 (s, 1H), 7.94 - 7.83 (m, 2H), 7.80 (s, 1H), 7.72 (td, 7= 8.6, 2.9 Hz, 1H), 7.59 (dt, J = 5.9, 3.0 Hz, 1H), 7.48 - 7.39 (m, 2H), 7.43 -7.30 (m, 6H), 5.90 (s, 1H), 3.41 (s, 3H).

[0985] Example 127: N- [5-chloro-2- [hydroxy(phenyl)methyl] -4-oxo-quinazolin-3-yl] -4-methyl-benzenesulfonamide

[0986]

[0987] The title compound was obtained in analogy to Example 121 as a white solid (46.5% yield) by treating N-(2-{[(tert-butyldiphenylsilyl)oxy](phenyl)methyl}-5-chloro-4-oxoquinazolin-3-yl)-4-methylbenzenesulfonamide with triethylamine trihydrofluoride. LCMS (ESI): [M+H]+: 456.00. ’H NMR (300 MHz, DMSO-d6) δ 11.04 (s, 1H), 7.77 (t, J = 8.0 Hz, 1H), 7.71 - 7.61 (m, 3H), 7.53 (dd, 7= 7.8, 1.2 Hz, 1H), 7.33 (dddd, 7= 15.0, 7.6, 6.2, 2.3 Hz, 7H), 6.11 (s, 1H), 5.81 (s, 1H), 2.41 (s, 3H).

[0988] Example 128: 3-cyclopropyl-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0989]

[0990] The title compound was obtained in analogy to Example 6 as a white solid (4.5% yield) using 3-amino-6-fluoro-2-[methoxy(phenyl)methyl]quinazolin-4-one and 3-cyclopropylbenzenesulfonyl chloride. LCMS (ESI): [M + H]+: 480.13.!H NMR (400 MHz, DMSO-d6) 8 11.44 (s, 1H), 7.85 (d, J = 54.2 Hz, 2H), 7.60 - 7.55 (m, 2H), 7.48 -7.41 (m, 3H), 7.35 (s, 5H), 5.77 (s, 1H), 3.36 (s, 3H), 2.00 (ddd, J= 8.4, 5.0, 3.4 Hz, 1H), 0.99 - 0.95 (m, 2H), 0.62 (d, J = 34.6 Hz, 2H).

[0991] Example 129: 4-(dimethylamino)-N-(7-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[0992]

[0993] The title compound was obtained in analogy to Example 23 as a white solid (14.5% yield) using 4-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid and 4-fluoro-2-(2-methoxy-2-phenylacetamido)benzoic acid. LCMS (ESI): [M+H]+: 483.05.1H NMR (400 MHz, DMSO-d6) 6 10.94 (s, 1H), 7.96 (t, J= 7.5 Hz, 1H), 7.64 (d, J= 9.7 Hz, 1H), 7.55 - 7.47 (m, 2H), 7.44 - 7.30 (m, 6H), 6.73 (d, J = 8.8 Hz, 2H), 5.84 (s, 1H), 3.34 (s, 3H), 3.01 (s, 6H).

[0994] Example 130: 4-(dimethylamino)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-methyl-4-oxo-quinazolin-3-yl]benzenesulfonamide

[0995]

[0996] The title compound was obtained in analogy to Example 23 as a white solid (7.5% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]-3-methylbenzoic acid and N'-[4-(dimethylamino)benzenesulfonyl]tert-butoxycarbohydrazide. LCMS (ESI): m / z = 515.15 [M + H]+. ’H NMR (300 MHz, DMSO-d6) 8 10.22 - 10.60 (s, 1H), 7.62 - 7.53 (m, 3H), 7.53 - 7.39 (m, 3H), 7.14 (t, J = 8.9 Hz, 2H), 6.75 (d, J= 9.1 Hz, 2H), 5.94 (s, 1H), 3.40 (s, 3H), 3.03 (s, 6H), 2.51 (s, 3H).

[0997] Example 131: N-[6-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(l,l-difluoroethyl)benzenesulfonamide

[0998]

[0999] The title compound was obtained in analogy to Example 23 as a white solid (28.2% yield) using 5-chloro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and 7V’-[4-(l, 1 -difluorocthyl)bcnzcncsulfonyl| / e / -butoxycarbohydrazidc. LCMS (ESI): [M+H]+: 538.05. ’H NMR (400 MHz, DMSO-d6) 6 11.75 (s, 1H), 7.92 - 7.62 (m, 7H), 7.49 - 7.40 (m, 2H), 7.22 (t, J = 8.8 Hz, 2H), 5.85 (s, 1H), 3.37 (s, 3H), 2.06 (s, 3H).

[1000] Example 132: N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(l-hydroxy-l-methyl-ethyl)benzenesulfonamide

[1001]

[1002] a) 4-[2-(benzyloxy)propan-2-yl]-A-{6-fhioro-2-[(4-fhiorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}benzenesulfonamide

[1003] The title compound was obtained in analogy to Example 23 as a white solid (39.8% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-{4-[2-(benzyloxy)propan-2-yl]benzenesulfonyl}tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 606.

[1004] b) N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(l-hydroxy- 1 -methyl-ethyl)benzenesulfonamide

[1005] A solution of 4-[2-(benzyloxy)propan-2-yl]-A-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}benzenesulfonamide (300 mg, 0.49 mmol, 1 equiv) and TiCU (375.8 mg, 1.98 mmol, 4 equiv) in DCM (5 mL) was stirred for 1 h at room temperature under nitrogen atmosphere. The resulting mixture was extracted with EtOAc (2 x 10 mL). The combined organic layers were washed with H2O (2 x 10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 90% gradient in 60 min; detector, UV 254 nm. This resulted in A-{6-fluoro-2-[(4-fhiorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-(2-hydroxypropan-2-yl)benzenesulfonamide (44.3 mg, 17.30% yield) as a white solid. LCMS (ESI): [M+H]+: 516.10. ’H NMR (400 MHz, DMSO-d6) δ 11.36 (s, 1H), 7.90 (d, J= 6.3 Hz, 1H), 7.79 (s, 1H), 7.73 (d, 7= 8.3 Hz, 3H), 7.67 (d, J = 8.2 Hz, 3H), 7.57 (d, J = 8.0 Hz, 1H), 7.37 (t, J = 7.0 Hz, 1H), 7.23 - 7.14 (m, 1H), 5.69 (s, 1H), 5.31 (s, 1H), 3.36 - 3.28 (m, 3H), 1.44 (d, J= 1.3 Hz, 6H).

[1006] Example 133: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(2-methoxypropyl)benzenesulfonamide

[1007]

[1008] The title compound was obtained in analogy to Example 87 as a white solid (12.4% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2-methoxypropyl)benzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 512.25.!H NMR (400 MHz, Acetonitrile-d3) 68.61 (s, 1H), 7.81 -7.63 (m, 3H), 7.63 -7.53 (m, 1H), 7.51 -7.41 (m, 1H), 7.42 - 7.23 (m, 7H), 5.85 (d, J= 1.5 Hz, 1H), 3.64 - 3.51 (m, 1H), 3.42 (d, J = 1.2 Hz, 3H), 3.25 (d, J= 0.7 Hz, 3H), 2.94 - 2.85 (m, 1H), 2.81 - 2.61 (m, 1H), 1.13 -1.01 (m, 3H).

[1009] Example 134: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethoxy)benzenesulfonamide

[1010]

[1011] The title compound was obtained in analogy to Example 87 as a white solid (26.7% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2,2-trifluoroethoxy)benzenesulfonyl chloride. MS (ESIpos): m / z = 538.10 [M+H]+. ’H NMR (400 MHz, DMSO-d6) 5 11.43 (s, 1H), 7.96 - 7.68 (m, 4H), 7.65 - 7.29 (m, 6H), 7.26 - 7.17 (m, 2H), 5.88 (s, 1H), 4.92 (q, J= 8.8 Hz, 2H), 3.38 (s, 3H).

[1012] Example 135: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide

[1013]

[1014] The title compound was obtained in analogy to Example 87 as a white solid (13.3% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and p-toluenesulfonyl chloride. LC-MS (ES, m / z): [M+l] = 454.12. ’H NMR (400 MHz, DMSO-d6) 5 11.42 (s, 1H), 7.89 (s, 1H), 7.76 (s, 1H), 7.71 - 7.57 (m, 3H), 7.42 - 7.30 (m, 7H), 5.83 (s, 1H), 3.35 (s, 3H), 2.41 (s, 3H).

[1015] Example 136: 4-(l-cyanocyclopropyl)-N-[6-fhioro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[1016]

[1017] The title compound was obtained in analogy to Example 87 as a white solid (16.0% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(l-cyanocyclopropyl)benzenesulfonyl chloride. LC-MS (ES, m / z): [M+l] = 505.!H NMR (400 MHz, Acetonitrile-d3) 68.69 (s, 1H), 7.81 - 7.74 (m, 2H), 7.73 (s, 1H), 7.60 (t, J = 8.7, 3.0 Hz, 1H), 7.51 (dd, J = 8.5, 3.0 Hz, 1H), 7.47 - 7.37 (m, 4H), 7.40 - 7.29 (m, 3H), 5.84 (s, 1H), 3.43 (s, 3H), 1.85 (d, J = 4.6, 3.2 Hz, 2H), 1.62 - 1.49 (m, 2H).

[1018] Example 137: 4-(difluoromethoxymethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[1019]

[1020] The title compound was obtained in analogy to Example 87 as a white solid (16.6% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-[(difluoromethoxy)methyl]benzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+:

[1021] 520.10. ’H NMR (400 MHz, DMSO-d6) 6 11.73 (d, J= 136.3 Hz, 1H), 7.95 - 7.73 (m, 3H), 7.58 (d, J= 8.1 Hz, 3H), 7.38 (s, 6H), 6.85 (d, J= 75.3 Hz, 1H), 5.82 (s, 1H), 5.05 (s, 2H), 3.36 (s, 3H).

[1022] Example 138: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(oxazol-2-ylmethyl)benzenesulfonamide

[1023]

[1024] The title compound was obtained in analogy to Example 87 as a white solid (21.8% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(l,3-oxazol-2-ylmethyl)benzenesulfonyl chloride. LCMS (ESI): [M+H]+: 521.12. ’H NMR (400 MHz, Acetonitrile-d3) 68.66 (s, 1H), 7.80 - 7.69 (m, 4H), 7.63 - 7.55 (m, 1H), 7.50 -7.36 (m, 5H), 7.37 - 7.28 (m, 3H), 7.07 (s, 1H), 5.82 (s, 1H), 4.22 (s, 2H), 3.40 (d, J= 1.1 Hz, 3H).

[1025] Example 139: N-[8-(fluoromethyl)-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide

[1026]

[1027] a) N- { 8-[(benzyloxy)methyl] -2-[methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl } -4-methylbenzenesulfonamide

[1028] The title compound was obtained in analogy to Example 23 as a white solid (37.3% yield) using 3-[(benzyloxy)methyl]-2-(2-methoxy-2-phenylacetamido)benzoic acid and N'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 556.1.

[1029] b) A-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide

[1030] A-{8-[(benzyloxy)methyl]-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (2.10 g, 3.779 mmol, 1.0 equiv) in DCM (30 mL) was added Titanium tetrachloride (716.8 mg, 3.779 mmol, 1.0 equiv) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 20 min under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH₂Cl₂ / MeOH (10:1) to afford A-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (1 g, 56.84% yield, 50% purity) as a yellow solid. LCMS (ESI) [M + H]+: 466.1.

[1031] c) N-[8-(fhioromethyl)-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide

[1032] To a stirred solution of A-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4- methylbenzenesulfonamide (200.0 mg, 0.430 mmol, 1.0 equiv) in DCM (5 mL) was added DAST (69.2 mg, 0.430 mmol, 1.0 equiv) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 30 min under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column:

[1033] XSelect CSH Fluoro Phenyl 30*150 mm, 5m; Mobile Phase A: Water(0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 39% B to 59% B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 12.5) to afford N- [8-(fhioromethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (87 mg, 43.31% yield) as a white solid. Chiral separation using conditions F afforded N-[8-(fhioromethyl)-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide (36.8% yield, RT=9.0min, first peak) as a white solid. LCMS (ESI):

[1034] [M+H]+: 468.15. ’H NMR (400 MHz, DMSO-d6) 5 11.92 - 11.17 (m, 1H), 8.01 -7.86 (m, 2H), 7.73 - 7.64 (m, 2H), 7.62 - 7.51 (m, 1H), 7.47 - 7.26 (m, 7H), 6.06 - 5.38 (m, 3H), 3.37 (s, 3H), 2.41 (s, 3H).

[1035] Example 140: N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-methyl-4-oxo-quinazolin-3-yl]-l-methyl-indole-6-sulfonamide

[1036]

[1037] The title compound was obtained in analogy to Example 23 as a white solid (14.3% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]-3-methylbenzoic acid and N'-(1-methylindol-6-ylsulfonyl)tert-butoxycarbohydrazide. LCMS (ESI): [M+H]+: 525.14. ’H NMR (400 MHz, Acetonitrile-d3) 68.55 (s, 1H), 7.79 (s, 1H), 7.71 (d, J= 8.4 Hz, 1H), 7.49 - 7.39 (m, 5H), 7.17 (dd, J= 8.4, 3.0 Hz, 1H), 7.07 (t, J= 8.5 Hz, 2H), 6.60 (dt, J = 3.1, 0.8 Hz, 1H), 5.76 (s, 1H), 3.68 (s, 3H), 3.36 (s, 3H), 2.13 (s, 3H).

[1038] Example 141: N-[8-(fluoromethyl)-4-oxo-2-[(S)-methoxy(phenyl)methyl]quinazolin-3-yl] -4-methyl-benzenesulfonamide

[1039]

[1040] The title compound was the second peak from the chiral separation of A-[8-(fhioromethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (Example 139) using conditions F (36.8% yield, RT=11.0min, second peak) as a white solid. LCMS (ESI): [M+H]+: 468.15. ’H NMR (400 MHz, DMSO- d6) δ 11.92 – 11.28 (m, 1H), 8.03 - 7.85 (m, 2H), 7.71 - 7.64 (m, 2H), 7.62 - 7.53 (m, 1H), 7.47 -7.28 (m, 7H), 6.13 -5.35 (m, 3H), 3.37 (s, 3H), 2.41 (s, 3H).

[1041] Example 142: N- [[4- [[6-fluoro-4-oxo-2- [(R)-methoxy(phenyl)methyl] quinazolin-3-yl] sulfamoyl] phenyl] methyl] acetamide

[1042]

[1043] The title compound was obtained in analogy to Example 87 as a white solid (15.5% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(acetamidomethyl)benzenesulfonyl chloride. LCMS (ESI) [M+H]+: 511.14.!H NMR (400 MHz, DMSO-d6) 8 11.46 (s, 1H), 8.48 (t, J= 6.1 Hz, 1H), 7.91 (s, 1H), 7.75 (d, J= 8.2 Hz, 3H), 7.60 (d, J = 8.3 Hz, 1H), 7.43 (d, J = 8.1 Hz, 2H), 7.37 (s, 5H), 5.78 (s, 1H), 4.36 (d, J = 6.0 Hz, 2H), 3.34 (s, 3H), 1.90 (s, 3H).

[1044] Example 143: N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide

[1045]

[1046] The title compound was obtained in analogy to Example 156 as a white solid (15.5% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]-8-methylquinazolin-4-one and 5-methylthiophene-2-sulfonyl chloride. LCMS (ESI) [M + H]+: 474.10. ’H NMR (400 MHz, Acetonitrile-d3) 68.60 (s, 1H), 7.51 - 7.29 (m, 8H), 6.83 (dq, J= 3.6, 1.1 Hz, 1H), 5.86 (s, 1H), 3.45 (d, J= 1.6 Hz, 3H), 2.69 - 2.49 (m, 6H). Example 144: N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]- 5-methyl-thiophene-2-sulfonamide

[1047] 0=^=0 o

[1048]

[1049] The title compound was obtained in analogy to Example 156 as a white solid (29.1% yield) using 3-amino-6,8-difluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 5-methylthiophene-2- sulfonyl chloride. LCMS (ESI) [M+H]+: 478.00.!H NMR (400 MHz, DMSO-d6) 5 11.85 (d, J= 141.2 Hz, 1H), 7.93 (s, 1H), 7.65 - 7.26 (m, 7H), 6.96 (s, 1H), 5.80 (s, 1H), 3.35 (d, J= 1.3 Hz, 3H), 2.69 - 2.52 (m, 3H).

[1050] Example 145: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide

[1051] o=s=o o

[1052]

[1053] The title compound was obtained in analogy to Example 87 as a white solid (44.5% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(1-fluorocyclopropyl)benzenesulfonyl chloride. LC-MS (ES, m / z): [M+l] = 531.0. ’H NMR (400 MHz, Acetonitrile-d3) 57.82 - 7.73 (m, 3H), 7.48 (dd, J = 8.0, 2.8 Hz, 1H), 7.43 (dt, J= 6.8, 2.5 Hz, 2H), 7.35 (tdd, J= 7.0, 5.3, 2.8 Hz, 5H), 5.87 (s, 1H), 3.43 (s,3 H), 1.68 -1.52 (m, 2H), 1.26 - 1.16 (m, 2H).

[1054] Example 146: 4-(2,2-difluoro-3-methoxy-propyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[1055]

[1056] The title compound was obtained in analogy to Example 87 as a white solid (28.1% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluoro-3-methoxypropyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 584.15.1H NMR (400 MHz, Acetonitrile-d3) 68.70 (s, 1H), 7.87 - 7.71 (m, 3H), 7.60 (d, J= 8.9 Hz, 1H), 7.49 - 7.28 (m, 8H), 5.87 (s, 1H), 3.55 - 3.46 (m, 2H), 3.43 (s, 3H), 3.39 (s, 3H), 3.33 (s, 2H).

[1057] Example 147: 4-(2,2-difluorocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[1058] o=s=o o

[1059]

[1060] The title compound was obtained in analogy to Example 87 as a white solid (58.7% yield) using 3-amino-6,8-difluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluorocyclopropyl) benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 534.2.1H NMR (400 MHz, DMSO-d6) 3 11.58 (s, 1H), 7.94 (t, J= 9.3 Hz, 1H), 7.77 (dd, J= 8.5, 3.3 Hz, 2H), 7.53 - 7.44 (m, 2H), 7.38 (d, J= 18.6 Hz, 6H), 5.79 (d, J= 8.3 Hz, 1H), 3.35 (d, J = 5.0 Hz, 3H), 3.19 (dt, J= 12.8, 10.0 Hz, 1H), 2.16 - 2.04 (m, 2H).

[1061] Example 148: N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide o=s=o o

[1062]

[1063] The title compound was obtained in analogy to Example 156 as a white solid (33.9% yield) using 3-amino-6,8-difluoro-2-[(7?)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(l-fluorocyclopropyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 516.10.!H NMR (400 MHz, Acetonitrile-d3) 68.65 (s, 1H), 7.80 - 7.76 (m, 2H), 7.48 (ddd, J= 10.2, 8.8, 2.9 Hz, 1H), 7.43 - 7.39 (m, 2H), 7.39 - 7.32 (m, 6H), 5.84 (s, 1H), 3.42 (s, 3H), 1.65 -1.56 (m, 2H), 1.27 - 1.16 (m, 2H).

[1064] Example 149: N-[8-[(3,3-difluorocyclobutyl)methylamino]-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide F

[1065] o=s=o o

[1066]

[1067] a) A-{6-fhioro-2-[(4-fhiorophenyl)(methoxy)methyl]-8-iodo-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide

[1068] The title compound was obtained in analogy to Example 6 as a yellow solid (55.6% yield) using 3-amino-6-fhioro-2-[(4-fhiorophenyl)(methoxy)methyl]-8-iodoquinazolin-4-one and p-toluenesulfonyl chloride. LC-MS (ESI, m / z): [M + H]+: 598.0.

[1069] b) N-[8-[(3,3-difhiorocyclobutyl)methylamino]-6-fhioro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[1070] To a stirred solution of A-{6-fluoro-2-[(4-fluorophenyl) (methoxy)methyl]-8-iodo-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (200 mg, 0.335 mmol, 1 equiv), Cs2CO3(327.25 mg, 1.005 mmol, 3 equiv) and l-(3,3-difluorocyclobutyl) methanamine hydrochloride (63.31 mg, 0.402 mmol, 1.2 equiv) in 1,4-dioxane (2 mL) were added Pd2(dba)3 (30.66 mg, 0.034 mmol, 0.1 equiv) andXantphos (19.37 mg, 0.034 mmol, 0.1 equiv) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred at 100 °C for 2 h under nitrogen atmosphere. The mixture was allowed to cool down to room temperature. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (3 x 10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Fluoro Phenyl 30*150 mm, 5pm; Mobile Phase A: Water(0.1%FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 43% B to58 % B in 14 min; Wave Length: 254nm / 220nm; RTl(min): 13.38) to affordA-(8-{[(3,3-difhiorocyclobutyl)methyl]amino}-6-fhioro-2-[(4-fhiorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl)-4-methylbenzenesulfonamide (30.6 mg, 15.48% yield, 97.7% purity) as a yellow solid. LC-MS (ESI, m / z): [M + H]+: 591.15.!H NMR (400 MHz, Chloroform-d) δ 8.11 (s, 1H), 7.62 (d, J = 8.3 Hz, 2H), 7.50 (s, 2H), 7.26 -7.21 (m, 2H), 7.08 (s, 2H), 6.63 - 6.58 (m, 1H), 6.46 (s, 1H), 6.16 (s, 1H), 5.16 (s, 1H) 3.56 (s, 3H), 3.26 (d, J= 75.9 Hz, 2H), 2.74 (s, 2H), 2.43 (s, 6H).

[1071] Example 150: N-[8-(azetidin-l-yl)-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[1072]

[1073] The title compound was obtained in analogy to Example 149 as a yellowish solid (33.6% yield) using A-{6-fluoro-2-[(4-fluorophenyl) (methoxy)methyl]-8-iodo-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide and azetidine hydrochloride. LC-MS (ESI, m / z): [M + H]+: 527.05.1H NMR (400 MHz, Acetonitrile-d3) δ 8.72 (s, 1H), 7.70 - 7.64 (m, 2H), 7.42 -7.36 (m, 2H), 7.34 (d, J= 8.1 Hz, 2H), 7.10 (t, J= 8.7 Hz, 2H), 6.67 - 6.62 (m, 1H), 6.38 - 6.27 (m, 1H), 5.81 (s, 1H), 4.24 - 3.88 (m, 4H), 3.43 (s, 3H), 2.42 (s, 3H), 2.27 (d, J = 9.6 Hz, 2H).

[1074] Example 151: 4-[(2,2-difluorocyclopropyl)methyl]-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide F

[1075]

[1076] F

[1077] The title compound was obtained in analogy to Example 87 as a white solid (15.0% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-[(2,2-difluorocyclopropyl)methyl]benzenesulfonyl chloride. LC-MS (ES, m / z): [M+l] = 530.!H NMR (400 MHz, Acetonitrile-d3) 68.52 (s, 1H), 7.77 - 7.70 (m, 3H), 7.59 (td, J= 8.7, 3.0 Hz, 1H), 7.49 (dd, J = 8.5, 3.0 Hz, 1H), 7.46 - 7.37 (m, 3H), 7.35 (s, 2H), 7.39 - 7.31 (m, 2H), 5.83 (s, 1H), 3.41 (s, 3H), 2.89 (s, 2H), 1.96 - 1.83 (m, 1H), 1.62 - 1.49 (m, 1H), 1.21 (s, 1H).

[1078] Example 152: N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxo-8-(2,2,2-trifluoroethyl)quinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1079] F

[1080] o=s=oo

[1081]

[1082] a) N-{8-bromo-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide

[1083] The title compound was obtained in analogy to Example 23 as a white solid

[1084]

[1085] yield) using 3-bromo-5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS(ESI) [M + H]+: 550.

[1086] b) N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxo-8-(2,2,2-trifluoroethyl)quinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1087] A solution of trifluoroethanol (181.8 mg, 1.815 mmol, 5 equiv) in 2-methoxy-2-methylpropane (2 mL) was added 5,7-di-tert-butyl-3-phenylbenzo[d]oxazol-3-ium tetrafluoroborate (430.9 mg, 1.089 mmol, 3 equiv) at 0 °C under nitrogen atmosphere followed by the addition of pyridine. (86.2 mg, 1.089 mmol, 3 equiv) dropwise at 0 °C. The resulting mixture was stirred at 0 °C for 30 min under nitrogen atmosphere. The resulting mixture was filtered, the filtrate was injected into a 8 mL vial which contained N-{8-bromo-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (200 mg, 0.363 mmol, 1 equiv), l-azabicyclo[2.2.2]octane (70.7 mg, 0.635 mmol, 1.75 equiv), 2,3-dihydro-1H-isoindole-1,3-dione (12.0 mg, 0.082 mmol, 0.225 equiv), A, A-dimethylacetamide (2 mL), [4,4'-Bis(tert-butyl)-2,2'-bipyridine] nickel dibromide (8.9 mg, 0.018 mmol, 0.05 equiv) and Ir[PPy]2(dtbbpy)PF6 (5.0 mg, 0.005 mmol, 0.015 equiv) at room temperature under N2 atmosphere. The resulting reaction mixture was irradiated with blue LED (450 nm) radiation at room temperature for 3 h. Then it was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 20 min, UV 254 nm to afford N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxo-8-(2,2,2-trifluoroethyl)quinazolin-3(4H)-yl)-4-methylbenzenesulfonamide (19.9 mg, 9.9% yield) as a white solid. LCMS(ESI) [M + H]+: 554.10. ’H NMR (400 MHz, Acetonitrile-d3) 59.05 - 8.41 (m, 1H), 7.73 - 7.60 (m, 3H), 7.54 (dd, J= 8.3, 3.0 Hz, 1H), 7.49 - 7.41 (m, 2H), 7.35 (d, J= 8.1 Hz, 2H), 7.10 (t, J = 8.9 Hz, 2H), 5.84 (s, 1H), 3.97 (s, 2H), 3.43 (s, 3H), 2.43 (s, 3H).

[1088] Example 153: (R)-N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin- 3(4H)-yl)-5-methylthiophene-2-sulfonamide

[1089]

[1090] The title compound was obtained in analogy to Example 87 as a white solid (40.7% yield) using 3-amino-8-chloro-6-fhioro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 5-methylthiophene-2- sulfonyl chloride. LCMS (ESI) [M + H]+: 493.9.!H NMR (400 MHz, Acetonitrile-d3) 57.81 - 7.76 (m, 1H), 7.59 - 7.55 (m, 1H), 7.48 - 7.43 (m, 2H), 7.41 -7.32 (m, 4H), 6.82 (dt, J= 3.7, 1.1 Hz, 1H), 5.86 (s, 1H), 3.44 (s, 3H), 2.52 (d, J= 1.0 Hz, 3H).

[1091] Example 154: (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1092]

[1093] N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4- me thy Ibenzene sulfonamide was obtained in analogy to Example 23 as a white solid (46.2% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and -(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. Chiral separation using conditions C afforded (R)-N-(6,8-difhioro-2-((4-fhiorophenyl)(methoxy)methyl)-4- oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide (32.3% yield, RT=7.93min, first peak) as a white solid. LCMS (ESI) [M+H]+: 490.10. ’H NMR (300 MHz, DMSO-d6) 8 11.67 (d, J = 119.4 Hz, 1H), 7.92 (s, 1H), 7.69 (d, J = 8.2 Hz, 2H), 7.54 - 7.35 (m, 5H), 7.22 (d, J= 9.1 Hz, 2H), 5.79 (s, 1H), 3.35 (s, 3H), 2.41 (s, 3H).

[1094] Example 155: (R)-N-(8-(2,2-difluoroethoxy)-2-((4-fluorophenyl)(methoxy)methyl)-4- oxoquinazolin-3(4H)-yl)-4-(l-fluorocyclopropyl)benzenesulfonamide

[1095] F

[1096]

[1097] N-(8-(2,2-difhioroethoxy)-2-((4-fhiorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)- yl)-4-(l-fluorocyclopropyl)benzenesulfonamide was obtained in analogy to Example 6 as a white solid (39.4% yield) using 3-amino-8-(2,2-difhioroethoxy)-2-[(4- fluorophenyl)(methoxy)methyl] quinazolin-4-one and 4-(l- fluorocyclopropyl)benzenesulfonyl chloride. Chiral separation using conditions C afforded (R)-N-(8-(2,2-difluoroethoxy)-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin- 3(4H)-yl)-4-(l-fluorocyclopropyl)benzenesulfonamide (39.0% yield, RT=6.0min, first peak) as a white solid. LCMS (ESI, m / z): [M+ H]+: 578.00.1H NMR (400 MHz, DMSO- d6) δ 11.47 (s, 1H), 7.77 (d, J= 8.3 Hz, 2H), 7.64 - 7.32 (m, 7H), 7.21 (d, J= 8.2 Hz, 2H), 6.76 - 6.01 (m, 1H), 5.83 (d, J= 15.3 Hz, 1H), 4.69 - 4.45 (m, 1H), 4.22 (s, 1H), 3.38 (s, 3H), 1.79 - 1.47 (m, 2H), 1.41 - 1.11 (m, 2H).

[1098] Example 156: N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(l-fluorocyclobutyl)benzenesulfonamide

[1099] o=s=oo

[1100]

[1101] a) (R)-6,8-difluoro-2-(methoxy(phenyl)methyl)-4H-benzo[d][l,3]oxazin-4-one

[1102] A solution of 3,5-difhioro-2-[(2R)-2-methoxy-2-phenylacetamido]benzoic acid (8 g, 24.90 mmol, 1.00 equiv) in acetic anhydride (100 mL) was stirred at 50°C for 3 hours under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure to afford (R)-6,8-difhioro-2-(methoxy(phenyl)methyl)-4H-benzo[d][l,3]oxazin-4-one (5 g, 66.21% yield) as a yellow oil. LCMS (ESI) [M + H]+: 303.10.

[1103] b) 3-amino-6,8-difluoro-2-|( / ?)-mcthoxy(phcnyl)mcthyl|c|uinazolin-4-onc

[1104] A solution of (R)-6,8-difhioro-2-(methoxy(phenyl)methyl)-4H-benzo[d][l,3]oxazin-4-one (5.00 g, 16.40 mmol, 1.00 equiv) in EtOH (50 mL) was added hydrazine (2.64 g, 82.40 mmol, 5.00 equiv) at room temperature. The resulting mixture was stirred at 80°C for 2 hours under nitrogen atmosphere, water was added and then the resulting mixture was extracted with EtOAc (3 x 30 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by reverse phase flash with the following conditions (column, C18 silica gel; mobile phase, MeCN in Water (1% FA system), 40% to 60% gradient in 15 min; UV 254 nm) to afford 3-amino-6,8-difluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one (2.6 g, 44.07% yield, 71.14% ee) as a yellow solid. Chiral separation using conditions I afforded 3-amino-6,8-difluoro-2-|( / ?)-methoxy(phenyl)methyl]quinazolin-4-one (84.6% yield, RT=6.57min, first peak) as a brown solid. LCMS (ESI) [M + H]+: 318.00.

[1105] c) A-{6,8-difluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl }-4-iodobenzenesulfonamide A solution of 3-amino-6,8-difhioro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one, the first peak (200 mg, 0.630 mmol, 1 equiv) in THF (3 mL) was treated with LiHMDS (210.9 mg, 1.260 mmol, 2 equiv) at -78 °C for 30 min under nitrogen atmosphere followed by the addition of 4-iodobenzene sulfonyl chloride (228.8 mg, 0.756 mmol, 1.2 equiv) dropwise at -78 °C. The resulting mixture was stirred at -78 °C for 2 h under nitrogen atmosphere. The reaction was quenched with water at 0 °C. The residue was purified by reversed-phase flash chromatography with the following conditions: column, Cl 8 silica gel; mobile phase, MeCN in Water (0.1% FA), 10% to 50% gradient in 20 min, UV 254 nm to afford A-{6,8-difhioro-2-[(R)-methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl } -4-iodobenzenesulfonamide (270 mg, 73.43% yield) as a white solid. LCMS (ESI) [M + H]+: 584.0.

[1106] d) N-[6,8-difhioro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(l-fluorocyclobutyl)benzenesulfonamide

[1107] A solution of A-{6,8-difluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzene sulfonamide (120 mg, 0.206 mmol, 1 equiv), 1 -fluorocyclobutane- 1-carboxylic acid (48.6 mg, 0.412 mmol, 2 equiv), dtbpy (8.3 mg, 0.031 mmol, 0.15 equiv), Cs2CO3(134.1 mg, 0.412 mmol, 2 equiv), Ir[dF(CF3)ppy]2(dtbpy))PF6 (2.3 mg, 0.002 mmol, 0.01 equiv) and dichloronickel; 1,2-dimethoxyethane (4.5 mg, 0.021 mmol, 0.1 equiv) in DMF (4 mL) was stirred at room temperature for 16 h under nitrogen atmosphere. The reaction in photoreactor system under 450 nm blue LEDs. Desired product could be detected by LCMS. The resulting mixture was filtered, the filter cake was washed with acetonitrile (10 mL). The filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18, 30*150mm 5pm; Mobile Phase A: Water (0.1% PA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: isocratic 47% to 62% B in 12 min; Wave Length: 254 nm / 220 nm; RTl(min): 11.93 min to afford A-{6,8-difluoro-2-[(R)-methoxy(phenyl) methyl] -4-oxoquinazolin-3-yl } -4-( 1 -fluorocyclobutyl)benzenesulfonamide (6.2 mg, 5.69% yield, 96.2% purity) as a white solid. LCMS (ESI) [M + H]+: 530.20. ’H NMR (400 MHz, DMSO-d6) 6 11.68 (s, 1H), 7.83 (d, J = 8.2 Hz, 3H), 7.67 (d, J = 8.1 Hz, 2H), 7.49 - 7.28 (m, 6H), 5.86 (s, 1H), 3.33 (s, 3H), 2.72 - 2.53 (m, 4H), 2.06 (s, 1H), 1.77 (p, J= 9.1, 8.6 Hz, 1H).

[1108] Example 157: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-cyanocyclopropyl)benzenesulfonamide F

[1109] o=s=oo

[1110]

[1111] The title compound was obtained in analogy to Example 156 as a white solid (9.7% yield) using (R)-3-amino-8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)quinazolin-4(37 )-one and 4-(l-cyanocyclopropyl)benzenesulfonyl chloride. LC-MS (ESI, m / z) [M + H]+: 557.10. ’H NMR (400 MHz, Acetonitrile-d3) 57.81 - 7.73 (m, 3H), 7.48 (dt, J= 6.7, 1.4 Hz, 2H), 7.49 - 7.39 (m, 3H), 7.15 - 7.05 (m, 2H), 5.88 (s, 1H), 3.42 (s, 3H), 1.89 -1.81 (m, 2H), 1.57 - 1.50 (m, 2H).

[1112] Example 158: N-[8-chloro-6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(2,2-difluorocyclopropyl)benzenesulfonamide

[1113]

[1114] The title compound was obtained in analogy to Example 87 as a white solid (42.4% yield) using 3-amino-8-chloro-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluorocyclopropyl)benzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 550.10. ’H NMR (400 MHz, DMSO-d6) 5 11.77 (d, J= 150.1 Hz, 1H), 8.19 - 8.00 (m, 1H), 7.84 -7.73 (m, 2H), 7.62- 7.53 (m, 1H), 7.49 (d, J= 8.1 Hz, 2H), 7.37 (s, 5H), 5.81 (d, J= 8.6 Hz, 1H), 3.38 (d, J= 5.2 Hz, 3H), 3.25 - 3.10 (m, 1H), 2.18 - 2.03 (m, 2H).

[1115] Example 159: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide

[1116]

[1117] The title compound was obtained in analogy to Example 156 as a white solid (45.1% yield) using 3-amino-8-chloro-6-fluoro-2-[(7?)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l-fluorocyclopropyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 550.10.!H NMR (400 MHz, Acetonitrile-d3) 67.77 (dd, J= 7.2, 5.3 Hz, 3H), 7.52 - 7.42 (m, 3H), 7.34 (d, J = 8.2 Hz, 2H), 7.10 (t, J = 8.9 Hz, 2H), 5.89 (s, 1H), 3.43 (s, 3H), 1.65 - 1.55 (m, 2H), 1.29 - 1.18 (m, 2H).

[1118] Example 160: N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-(isopropoxymethyl)-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide

[1119]

[1120] a) A-[8-(chloromethyl)-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl] -4-methylbenzenesulfonamide

[1121] The title compound was obtained in analogy to Example 23 as a white solid (40.5% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]-3-(hydroxymethyl)benzoic acid and A'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 520.0.

[1122] b) N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-(isopropoxymethyl)-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide A solution of isopropyl alcohol (127.1 mg, 2.120 mmol, 10.0 equiv) in DMF (2 mL) was treated with NaH (10.1 mg, 0.424 mmol, 2.0 equiv) at -4 °C for 5 min under nitrogen atmosphere followed by the addition of A-[8-(chloromethyl)-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (110.0 mg, 0.212 mmol, 1.0 equiv) at -4 °C. The resulting mixture was stirred at -4 °C for 1 h under nitrogen atmosphere. The reaction was quenched with sat. NH4CI (aq.) at -4 °C. The aqueous layer was extracted with EtOAc (3 x 20 mL). The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18, 30*150mm 5pm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: isocratic 50% to 68% B in 16 min; Wave Length: 254 nm / 220 nm; RTl(min): 15.07 min to afford A- { 6-fhioro-2- [(4-fhiorophenyl)(methoxy)methyl] -8-(isopropoxymethyl)-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (47.0 mg, 40.87% yield, 99.159% purity) as a white solid. LCMS (ESI) [M + H]+: 544.20.1H NMR (400 MHz, DMSO-d6) 8 11.61 (d, J= 154.1 Hz, 1H), 7.76 - 7.59 (m, 3H), 7.54 - 7.48 (m, 1H), 7.48 - 7.35 (m, 4H), 7.31 - 7.11 (m, 2H), 5.82 (s, 1H), 5.15 - 4.31 (m, 2H), 4.10- 3.44 (m, 1H), 3.36 (s, 3H), 2.41 (s, 3H), 1.16 (s, 6H).

[1123] Example 161: N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide

[1124]

[1125] N-[6,8-difhioro-4-oxo-2-[(4-fhiorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide was obtained in analogy to Example 23 as a white solid (68.9% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and A'-[4-(l-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. Chiral separation using conditions E afforded N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-fluorocyclopropyl)benzenesulfonamide (33.0% yield, RT= 9.4min, first peak) as a white solid. Example 162: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin- 3-yl]-4-morpholino-benzenesulfonamide

[1126] o=s=o o

[1127]

[1128] The title compound was obtained in analogy to Example 87 as a white solid (21.6% yield) using A-{8-chloro-6-fluoro-2-[(7?)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide and morpholine. LC-MS (ESI, m / z): [M+ H]+: 559.15.!H NMR (400 MHz, DMSO-d6) 6 11.38 (d, J= 162.5 Hz, 1H), 8.09 (d, J= 24.3 Hz, 1H), 7.68 -7.52 (m, 3H), 7.37 (s, 5H), 7.02 (d, J= 9.1 Hz, 2H), 5.84 (s, 1H), 3.86 - 3.62 (m, 4H), 3.36 (s, 3H), 3.29 (d, J = 9.9 Hz, 4H).

[1129] Example 163: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(lH-pyrrol-2-yl)benzenesulfonamide

[1130]

[1131] a) tert-butyl-2-[4-({6-fluoro-2-[(7?)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl } sulfamoyl)phenyl] pyrrole- 1 -c arboxylate

[1132] To a stirred solution of A^-{6-fluoro-2-[(7?)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4 -iodobenzenesulfonamide (110 mg, 0.19 mmol, 1.0 equiv) and \-(lerl-butoxycarbonyl)pyrrol-2-ylboronic acid (82 mg, 0.39 mmol, 2.0 equiv) in dioxane (2 mL) and H2O (0.4 mL) were added Pd(dppf)Cl2 (14 mg, 0.02 mmol, 0.1 equiv) and K2CO3 (54 mg, 0.39 mmol, 2.0 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred at 80 °C for 1 h under nitrogen atmosphere. The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (3 x 20 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with petroleum ether / ethyl acetate (3:1) to afford / e / 7-butyl-2-|4-({6-fluoro-2-|( / ?)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}sulfamoyl)phenyl]pyrrole-l-carboxylate (80 mg, 68.00% yield, 100% purity) as a white solid. LC-MS (ESI, m / z): [M+ H]+: 605.0.

[1133] b) N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(lH-pyrrol-2-yl)benzenesulfonamide

[1134] To a stirred solution of tert-butyl-2-[4-({6-fhioro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl} sulfamoyl)phenyl] pyrrole- 1 -carboxylate (80 mg, 0.13 mmol, 1.0 equiv) in dichloromethane (1 mL) was added TFA (1 mL) in portions at room temperature under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 h under nitrogen atmosphere. The resulting mixture was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep Fluoro-Phenyl C18 Column, 30*150 mm, 5pm; Mobile Phase A: Water (0.1% formic acid), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min;

[1135] Gradient: 39% B to 69 % B in 10 min; Wave Length: 254nm / 220nm; RTl(min): 7.36 min to afford N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(lH-pyrrol-2-yl)benzenesulfonamide (17.3 mg, 25.92% yield, 97.3% purity) as a white solid.

[1136] LC-MS (ESI, m / z): [M+ H]+: 505.15. ’H NMR (400 MHz, DMSO-d6) 6 11.48 (d, J = 63.7 Hz, 2H), 7.97 - 7.59 (m, 7H), 7.54 - 7.26 (m, 5H), 6.98 (s, 1H), 6.74 (s, 1H), 6.23 - 6.13 (m, 1H), 5.91 (s, 1H), 3.36 (s, 3H).

[1137] Example 164: (R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin- 3(4H)-yl)-5-(2,2-difluoroethyl)thiophene-2-sulfonamide

[1138] o=s=oo

[1139]

[1140] a) 5-bromo-A-{6,8-difhioro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl } thiophene-2- sulfonamide The title compound was obtained in analogy to Example 156 as a white solid (43.9% yield) using 3-amino-6,8-difhioro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 5-bromothiophene-2- sulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 542.0.

[1141] b) (R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(2,2-difluoroethyl)thiophene-2-sulfonamide

[1142] To a stirred solution of 5-bromo-A-{6,8-difhioro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl} thiophene-2-sulfonamide (110 mg, 0.20 mmol, 1.0 equiv), l,l,l,3,3,3-hexamethyl-2-(trimethylsilyl)trisilane (51 mg, 0.20 mmol, 1.02 equiv), 2,6-dimethylpyridine (48 mg, 0.44 mmol, 2.2 equiv), and l,l-difluoro-2-iodoethane (116 mg, 0.61 mmol, 3.0 equiv) in 1,2-dimethoxyethane (2 mL) were added [4,4'-Bis(tert-butyl)-2, 2'-bipyridine] nickel dibromide (5 mg, 0.01 mmol, 0.05 equiv) and Ir[dF(CF3)ppy]2(dtbpy))PF6 (3 mg, 0.002 mmol, 0.01 equiv) dropwise at room temperature under nitrogen atmosphere. The final reaction mixture was irradiated with LED(450 nm) radiation at room temperature for overnight. The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (3 x 20 mL), dried over anhydrous Na2SO4E. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: XBridge Shield RP18 OBD Column 30*150 mm, 5pm; Mobile Phase A: Water (0.1% formic acid), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 38% B to 58% B inlO min; Wave Length: 254 nm / 220 nm; RTl(min): 10.98) to afford (R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(2,2-difluoroethyl)thiophene-2-sulfonamide (32.1 mg, 30.00% yield) as a white solid. LC-MS (ESI, m / z): [M+ H]+:

[1143] 528.10. ’H NMR (400 MHz, DMSO-d6) 6 11.97 (d, J= 144.8 Hz, 1H), 7.95 (s, 1H), 7.58 (d, J= 3.7 Hz, 1H), 7.50 (d, J= 8.1 Hz, 1H), 7.36 (s, 5H), 7.12 (d, J= 3.8 Hz, 1H), 6.46 -6.04 (m, 1H), 5.79 (s, 1H), 3.69 – 3.46 (m, 2H), 3.36 (s, 3H).

[1144] Example 165: (R)-N-(8-cyclopropoxy-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(l-fluorocyclopropyl)benzenesulfonamide F

[1145] O=S=O O

[1146]

[1147] N-(8-cyclopropoxy-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4- (l-fluorocyclopropyl)benzenesulfonamide was obtained in analogy to Example 6 as a white solid (54.6% yield) using 3-amino-8-cyclopropoxy-2-[(4- fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l- fluorocyclopropyl)benzenesulfonyl chloride. Chiral separation using conditions C afforded (R)-N-(8-cyclopropoxy-2-((4-fhiorophenyl)(rnethoxy)methyl)-4-oxoquinazolin-3(4H)-yl)- 4-(l-fhiorocyclopropyl)benzenesulfonamide (30.6% yield, RT=12.4min, first peak) as a white solid. LCMS(ESI) [M + H]+: 554. ’H NMR (400 MHz, DMSO-d6) 6 11.40 (s, 1H), 7.76 (d, J= 8.2 Hz, 3H), 7.53 - 7.30 (m, 6H), 7.19 (s, 2H), 5.80 (s, 1H), 4.05 (s, 1H), 3.34 (s, 3H), 1.61 (d, J = 19.5 Hz, 2H), 1.27 (s, 2H), 0.84 (d, J = 30.1 Hz, 4H).

[1148] Example 166: (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4- oxoquinazolin-3(4H)-yl)-5-methylthiophene-2-sulfonamide

[1149] F

[1150]

[1151] N-(6,8-difhioro-2-((4-fhiorophenyl)(rnethoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5- methylthiophene-2- sulfonamide was obtained in analogy to Example 23 as a white solid (41.1% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido] benzoic acid and A7-(5-methylthiophen-2-ylsulfonyl) tert-butoxycarbohydrazide. Chiral separation using conditions F afforded (R)-N-(6,8-difhioro-2-((4-fhiorophenyl)(methoxy)methyl)-4- oxoquinazolin-3(4H)-yl)-5-methylthiophene-2-sulfonamide (40.6% yield, RT=10.47min, first peak) as a white solid. LCMS(ESI) [M + H]+: 496.2.1H NMR (400 MHz, Acetonitrile-d3) d 7.54 - 7.41 (m, 4H), 7.41 (d, J= 3.8 Hz, 1H), 7.10 (t, J = 8.8 Hz, 2H), 6.83 (d, J= 3.8 Hz, 1H), 5.85 (s, 1H), 3.43 (s, 3H), 2.53 (s, 3H).

[1152] Example 167: (R)-N-(8-methoxy-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2-sulfonamide

[1153]

[1154] The title compound was obtained in analogy to Example 87 as a white solid (37.4% yield) using 3-amino-8-mcthoxy-2-|( / ?)-mcthoxy(phcnyl)mcthyl |quinazolin-4-onc and 5-methylthiophene-2- sulfonyl chloride. LCMS(ESI) [M + H]+: 472.15.!H NMR (400 MHz, Acetonitrile-d3) 68.67 (s, 1H), 7.51 - 7.45 (m, 1H), 7.44 - 7.38 (m, 4H), 7.38 - 7.29 (m, 4H), 6.81 (dd, J = 3.9, 1.1 Hz, 1H), 5.85 (s, 1H), 3.97 (s, 3H), 3.42 (s, 3H), 2.51 (d, J = 1.0 Hz, 3H).

[1155] Example 168: (R)-N-(8-(2,2-difluoroethyl)-6-fhioro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1156]

[1157] a) A-{8-bromo-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl} -4-methylbenzenesulfonamide

[1158] The title compound was obtained in analogy to Example 23 as a white solid (60.6% yield) using 3-bromo-5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LC-MS (ESI, m / z): [M+ H]+: 550.0. b) (R)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1159] To a stirred solution of A-{8-bromo-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin -3-yl}-4-methylbenzenesulfonamide (110 mg, 0.20 mmol, 1.0 equiv), 1,1-difluoro-2-iodoethane (115 mg, 0.60 mmol, 3.0 equiv), 1,1, 1,3,3, 3-hexamethyl-2-(trimethylsilyl)trisilane (51 mg, 0.20 mmol, 1.02 equiv) and 2,6-dimethylpyridine (47 mg, 0.44 mmol, 2.2 equiv) in 1,2-dimethoxyethane (2 mL) were added [4,4'-Bis(tert-butyl)-2, 2'-bipyridine] nickel dibromide (5 mg, 0.01 mmol, 0.05 equiv) and Ir[dF(CF3)ppy]2(dtbpy))PF6 (3 mg, 0.002 mmol, 0.01 equiv) in portions at room temperature under nitrogen atmosphere. The final reaction mixture was irradiated with blue LEDs (450 nm) radiation at room temperature for overnight. The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 30 mL). The combined organic layers were washed with brine (2 x 30 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18, 30*150mm 5pm; Mobile Phase A: Water (0.1% formic acid), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: isocratic 48% to 66% B in 13 min; Wave Length: 254 / 220 nm; RTl(min): 12.65 min) to afford N-[8-(2,2-difluoroethyl)-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4- oxoquinazolin-3-yl] -4-methylbenzenesulfonamide (90 mg, 84.09% yield) as a white solid. Chiral separation using conditions C afforded (R)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide (35.3% yield, RT=11.7min, first peak) as a white solid. LC-MS (ESI, m / z): [M+ H]+: 536.10. ’H NMR (400 MHz, DMSO-d6) 6 11.64 (d, J= 193.6 Hz, 1H), 7.81 (s, 1H), 7.75 -7.65 (m, 2H), 7.65 - 7.51 (m, 1H), 7.48 - 7.33 (m, 4H), 7.21 (s, 2H), 6.62 - 5.76 (m, 2H), 3.71 (s, 1H), 3.37 (s, 3H), 3.19 (s, 1H), 2.41 (s, 3H).

[1160] Example 169: (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide o=s=oo

[1161]

[1162] F F

[1163] a) 3-amino-8-chloro-6-fluoro-2-[(7?)-(4-fluorophenyl)(methoxy)methyl]quinazolin -4-one 3-amino-8-chloro-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one was obtained in analogy to Example 156 as a white solid (80.0% yield) using 8-chloro-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-3, l-benzoxazin-4-one and hydrazine monohydrate. Purification by chiral-HPLC using conditions D afforded 3-amino-8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one (45% yield, RT=3.65min, first peak) and 3-amino-8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)(methoxy)methyl]quinazolin -4-one (45% yield, RT=4.78min, second peak) as a white solid. LC-MS (ESI, m / z): [M+ H]+: 352.0.

[1164] b) (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide

[1165] To a stirred solution of 3-amino-8-chloro-6-fluoro-2-|( / ?)-(4-fluorophenyl)(methoxy)methyl] quinazolin-4-one (100 mg, 0.28 mmol, 1.0 equiv) and 4-[(difluoromethoxy)methyl]benzenesulfonyl chloride (109.45 mg, 0.426 mmol, 1.5 equiv) in THF (1 mL) was added LiHMDS (0.57 mL, 0.568 mmol, 2 equiv) in portions at -78 °C under nitrogen atmosphere. The resulting mixture was stirred at -78 °C for 1 h under nitrogen atmosphere. The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 20 mL). The combined organic layers were washed with brine (3x20 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep Fluoro-Phenyl C18 Column, 30*150 mm, 5pm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min; Gradient: 43% B to73 % B in 13 min; Wave Length: 254 / 220 nm; RTl(min): 9.2 min) to afford A-{8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)(methoxy) methyl] -4-oxoquinazolin-3-yl } -4-[(difluoromethoxy)methyl]benzenesulfonamide (63.0 mg, 38.75% yield) as a white solid. LC-MS (ESI, m / z): [M+ H]+: 572.10. ’H NMR (400 MHz, DMSO-d6) 6 11.81 (d, J = 169.7 Hz, 1H), 8.12 (s, 1H), 7.92 - 7.73 (m, 2H), 7.66 - 7.52 (m, 3H), 7.54 - 7.37 (m, 2H), 7.32 - 7.12 (m, 2H), 7.08 - 6.58 (m, 1H), 5.83 (s, 1H), 5.06 (s, 2H), 3.38 (s, 3H).

[1166] Example 170: 4-(2,2-difluorocyclopropoxy)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[1167]

[1168] The title compound was obtained in analogy to example 87 as a white solid (16.3% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-(2,2-difluorocyclopropoxy)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 532.10. ’H NMR (400 MHz, Acetonitrile-d3) 67.79 - 7.71 (m, 3H), 7.62 - 7.56 (m, 1H), 7.54 - 7.48 (m, 1H), 7.45 - 7.41 (m, 2H), 7.39 - 7.30 (m, 3H), 7.13 - 7.08 (m, 2H), 5.91 (d, J= 2.4 Hz, 1H), 4.41 - 4.33 (m, 1H), 3.43 (d, J= 1.8 Hz, 3H), 2.05 - 1.98 (m, 1H), 1.75 - 1.65 (m, 1H).

[1169] Example 171: (S)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide

[1170]

[1171] The title compound was obtained in analogy to example 169 as a white solid (43.3% yield) using 3-amino-8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-[(difluoromethoxy)methyl]benzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 572.05.1H NMR (400 MHz, DMSO-d6) 6 11.81 (d, J = 168.5 Hz, 1H), 8.12 (s, 1H), 7.83 (dd, J= 8.5, 1.8 Hz, 2H), 7.58 (td, J = 5.9, 2.9 Hz, 3H), 7.44 (s, 2H), 7.22 (t, J= 8.8 Hz, 2H), 6.85 (t, J = 75.3 Hz, 1H), 5.83 (s, 1H), 5.05 (s, 2H), 3.38 (s, 3H).

[1172] Example 172: (S)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1173]

[1174] The title compound was the second peak from the chiral separation of N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide (example 168) using conditions C (35.3% yield, RT=16.60min, second peak) as a white solid. LC-MS (ESI, m / z): [M+ H]+: 536.10.!H NMR (400 MHz, DMSO-d6) 6 11.64 (d, J= 191.2 Hz, 1H), 7.81 (s, 1H), 7.72 - 7.64 (m, 2H), 7.63 - 7.52 (m, 1H), 7.48 - 7.29 (m, 4H), 7.21 (s, 2H), 6.73 - 5.37 (m, 2H), 3.63 (d, J = 65.7 Hz, 1H), 3.37 (s, 3H), 3.21 (d, J = 65.7 Hz, 1H), 2.41 (s, 3H).

[1175] Example 173: 5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide

[1176]

[1177] a) 5-[(benzyloxy)methyl] -N- { 2- [(4-fluorophenyl)(methoxy)methyl] -8-methyl-4-oxoquinazolin-3-yl}thiophene-2-sulfonamide

[1178] The title compound was obtained in analogy to example 23 as a white solid (47.9% yield) using 2-[2-(4-fluorophenyl)-2-methoxyacetamido]-3-methylbenzoic acid and A-{5-[(benzyloxy)methyl]thiophen-2-ylsulfonyl}tert-butoxycarbohydrazide. LCMS (ESIpos): m / z = 580.00 [M+H]+.

[1179] b) A-{2-[(4-fhiorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl }-5-(hydroxymethyl)thiophene-2-sulfonamide

[1180] To a stirred solution of 5-[(benzyloxy)methyl]-A-{2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}thiophene-2-sulfonamide (350 mg, 0.604 mmol, 1 equiv) in DCM (10 mL) was added Titanium(IV) chloride (1.0 M in dichloromethane) (0.23 mL, 1.208 mmol, 2 equiv) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature overnight. Desired product could be detected by LCMS. The reaction was quenched by the addition of sat. NH4CI (aq.) (2 mL) at 0 °C. The resulting mixture was extracted with CH2Q2 (3 x 10 mL). The combined organic layers were washed with brine (3 x 10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH2Cl2 / MeOH (10:1) to afford A- {2- [(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-5-(hydroxymethyl)thiophene-2-sulfonamide (260 mg, 87.96% yield) as alight yellow solid. LCMS (ESIpos): m / z = 499.00 [M+H]+.

[1181] c) 5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide

[1182] To a stirred solution of A-{2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-5-(hydroxymethyl)thiophene-2-sulfonamide (130 mg, 0.266 mmol, 1 equiv) in DCM (10 mL) was added DAST (0.27 mL, 0.270 mmol, 1.02 equiv) in portions at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for additional 30 min. Desired product could be detected by LCMS. The reaction was quenched with ice water at 0 °C. The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Fluoro Phenyl 30*150 mm, 5pm; Mobile Phase A: Water (0.1%FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 45% B to 62% B in 16 min; Wave Length: 254 / 220 nm; RTl(min): 7.97 min) to afford 5-(fluoromethyl)-N-{2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}thiophene-2-sulfonamide (68.5 mg, 52.48% yield) as a white solid. LCMS (ESIpos): m / z = 492.00 [M+H]+.1H NMR (400 MHz, Acetonitrile-d3) δ 8.94 (s, 1H), 7.74 (d, J= 7.9 Hz, 1H), 7.69 (d, J= 7.5 Hz, 1H), 7.51 (dd, J= 3.9, 1.7 Hz, 3H), 7.38 (t, J= 7.7 Hz, 1H), 7.19 - 7.15 (m, 1H), 7.11 (t, J = 8.8 Hz, 2H), 5.88 (s, 1H), 5.60 (d, J = 0.7 Hz, 1H), 5.48 (d, J = 0.7 Hz, 1H), 3.47 (s, 3H), 2.57 (s, 3H).

[1183] Example 174: N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-3-methyl-lH-indole-6-sulfonamide

[1184]

[1185] a) N-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-3-nitro-4-(prop-1-en-2-yl)benzenesulfonamide

[1186] The title compound was obtained in analogy to example 6 as a white solid (55.1% yield) using 3-amino-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methylquinazolin-4-one and 3-nitro-4-(prop-l-en-2-yl)benzenesulfonyl chloride. LC-MS (ES, m / z): LCMS (ESI) [M+H]+: 557.12.

[1187] b) 3-amino-N-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-4-(prop-1-en-2-yl)benzenesulfonamide

[1188] To a stirred mixture of N-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-3-nitro-4-(prop-1-en-2-yl)benzenesulfonamide (250 mg, 0.449 mmol, 1 equiv) and B2(OH)4 (120.8 mg, 1.347 mmol, 3 equiv) in DMF (3 mL) was added 4-(pyridin-4-yl)pyridine (0.7 mg, 0.004 mmol, 0.01 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred for additional 0.5 h at 25 °C. The resulting mixture was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (10 mmol / L NH4HCO3), 50% to 70% gradient in 30 min; detector, UV 254 nm. This resulted in 3-amino-N-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-4-(prop-1-en-2-yl)benzenesulfonamide (220 mg, 93.01% yield) as a yellow solid. LCMS (ESI) [M+H]+: 527.12.

[1189] c) N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)- 3 -methyl- 1 H-indole- 6- sulfonamide To a stirred solution of 3-amino-A-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-4-(prop-l-en-2-yl)benzenesulfonamide (180 mg, 0.342 mmol, 1 equiv) and NaHCO3(86.1 mg, 1.026 mmol, 3 equiv) in ACN (5 mL) was added iodine (260.2 mg, 1.026 mmol, 3 equiv) at 0 °C. The resulting mixture was stirred for additional 2 h at 0 °C. The reaction was quenched with Na2SO4h at 0 °C. The resulting mixture was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: Column: XBridge Prep OBD C18 Column, 30*150 mm, 5pm; Mobile Phase A: Water (10 nmol / L NH4HCO3), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 22% B to 57 % B in 15 min; Wave Length: 254 / 220 nm; RTl(min): 11.67 min. This resulted in N-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl}-3-methyl-1H-indole-6-sulfonamide (25.1 mg, 14.00% yield) as a white solid. LCMS (ESI) [M+H]+: 525.12. ’H NMR (400 MHz, Acetonitrile-d3) 59.46 (d, J = 40.6 Hz, 1H), 8.56 (s, 1H), 7.77 (d, J = 37.5 Hz, 1H), 7.60 (dd, J = 43.3, 8.4 Hz, 1H), 7.50 - 7.36 (m, 4H), 7.33 - 7.30 (m, 1H), 7.22 (ddd, J = 8.5, 3.1, 0.8 Hz, 1H), 7.12 - 7.03 (m, 2H), 5.74 (s, 1H), 3.35 (d, J= 1.9 Hz, 3H), 2.64 (s, 2H), 2.45 (d, J= 0.9 Hz, 1H), 2.32 (d, J= 1.1 Hz, 3H).

[1190] Example 175: N-(8-(2,2-difluoroethoxy)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1191] F

[1192] o=s=oo

[1193]

[1194] The title compound was obtained in analogy to example 23 as a white solid (35.5% yield) using 3-(2,2-difluoroethoxy)-5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and A'-(4-methylbenzenesulfonyl)tert-butoxycarbohydrazide. LCMS (ESI) [M + H]+: 552.15. ’H NMR (400 MHz, Acetonitrile-d3) 68.50 (s, 1H), 7.71 - 7.65 (m, 2H), 7.44 (dd, J = 8.5, 5.5 Hz, 2H), 7.36 - 7.31 (m, 2H), 7.25 - 7.16 (m, 2H), 7.13 - 7.06 (m, 2H), 6.27 (t, J= 54.9 Hz, 1H), 5.83 (s, 1H), 4.41 (s, 2H), 3.40 (s, 3H), 2.43 (s, 3H).

[1195] Example 176: (R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide F

[1196] o=s=oo

[1197]

[1198] N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide was obtained in analogy to example 23 as a white solid (38.2% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-{4-[(difluoromethoxy)methyl]benzenesulfonyl}tert-butoxycarbohydrazide. Chiral separation using conditions E afforded (R)-N-(6,8-difluoro-2-((4-fhiorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide (32.5% yield, RT=8.24min, first peak) as a white solid. LCMS(ESI) [M + H]+: 556.1. ’H NMR (400 MHz, Acetonitrile-d3) 38.76 (s, 1H), 7.84 - 7.77 (m, 2H), 7.56 - 7.39 (m, 5H), 7.38 - 7.30 (m, 1H), 7.15 - 7.05 (m, 2H), 6.51 (s, 1H), 5.85 (s, 1H), 5.01 (s, 2H), 3.43 (s, 3H).

[1199] Example 177: (R)-4-(l-fluorocyclopropyl)-N-(8-(fluoromethyl)-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[1200]

[1201] 4-(l-fluorocyclopropyl)-N-(8-(fluoromethyl)-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide was obtained in analogy to example 81 as a white solid (54.8% yield) using 4-(l-fluorocyclopropyl)-N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide and DAST. Chiral separation using conditions E afforded (R)-4-(l-fluorocyclopropyl)-N-(8-(fluoromethyl)-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide (33.7% yield, RT=7.00min, first peak) as a white solid. LCMS (ESI) [M + H]+: 512.10. ’H NMR (400 MHz, Acetonitrile-d3) 67.91 (d, J = 7.4 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.81 - 7.75 (m, 2H), 7.55 - 7.48 (m, 1H), 7.47 - 7.41 (m, 2H), 7.40 - 7.31 (m, 5H), 5.99 - 5.69 (m, 3H), 3.45 (s, 3H), 1.66 - 1.54 (m, 2H), 1.29 - 1.17 (m, 2H).

[1202] Example 178: N-(6,8-difluoro-2-((S)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide

[1203]

[1204] a) A-{6,8-difhioro-2-[(4-fhiorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide

[1205] The title compound was obtained in analogy to example 23 as a white solid (94.0% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-(4-iodobenzenesulfonyl)tert-butoxycarbohydr azide

[1206] b): N-(6,8-difluoro-2-((S)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide

[1207] A solution of N-{6,8-difluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide (300 mg, 0.499 mmol, 1 equiv), (ls,3s)-3-fluorocyclobutan-1 -amine (89.8 mg, 1.008 mmol, 2.02 equiv), Pd2(dba)3 (91.4 mg, 0.100 mmol, 0.20 equiv), Xphos (92.8 mg, 0.195 mmol, 0.39 equiv) and DIPEA (192.2 mg, 1.487 mmol, 2.98 equiv) in dioxane (5 mL) was stirred at 100 °C for 1 h under nitrogen atmosphere. Desired product could be detected by LCMS. The resulting mixture was filtered, the filter cake was washed with dioxane (3 x 5 mL). The filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18, 30*150 mm 5pm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: MeOH-HPLC; Flow rate: 60 mL / min; Gradient: isocratic 53% to 71% B in 11 min; Wave Length: 254 / 220 nm; RT= 10.77 min) to afford N-{6,8-difluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-{[(1s,3s)-3-fluorocyclobutyl]amino}benzenesulfonamide (32 mg, 35.63% yield,) as a white solid. Chiral separation using conditions G afforded N-(6,8-difluoro-2-((S)-(4- fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide (28.1% yield, RT=3.72min, first peak) as a white solid. LCMS(ESI) [M + H]+: 563.15. ’H NMR (400 MHz, DMSO-d6) 6 11.17 (d, J = 175.1 Hz, 1H), 7.91 (s, 1H), 7.54 - 7.31 (m, 5H), 7.18 (s, 2H), 7.08 (d, J= 6.2 Hz, 1H), 6.55 (d, 7= 8.5 Hz, 2H), 5.80 (s, 1H), 5.00 - 4.78 (m, 1H), 3.47 (q, J = 7.6 Hz, 1H), 3.34 (s, 3H), 2.88 (d, J= 5.9 Hz, 2H), 2.03 (d, J= 22.7 Hz, 2H).

[1208] Example 179: N-(6,8-difluoro-2-((R)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide

[1209]

[1210] The title compound was the second peak from the chiral separation of N-(6,8-difluoro-2-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((ls,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide (example 178) using conditions G (33.8% yield, RT=5.93min, second peak) as a white solid. LCMS(ESI) [M + H]+: 563.15.!H NMR (400 MHz, DMSO-d6) 6 11.17 (d, J = 175.1 Hz, 1H), 7.90 (s, 1H), 7.54 - 7.31 (m, 5H), 7.19 (s, 2H), 7.08 (d, J= 6.2 Hz, 1H), 6.55 (d, J= 8.5 Hz, 2H), 5.81 (s, 1H), 5.00 -4.78 (m, 1H), 3.47 (q, J = 7.5 Hz, 1H), 3.34 (s, 3H), 2.88 (d, J = 5.9 Hz, 2H), 2.03 (d, J = 22.5 Hz, 2H).

[1211] Example 180: (R)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide

[1212]

[1213] The title compound was the first peak from the chiral separation of 5-(fhioromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide (example 173) using conditions E (38.6% yield, RT=7.26min, first peak) as a white solid. LCMS(ESI) [M + H] +: 492.10. ’H NMR (400 MHz, Acetonitrile-d3) 67.76 -7.67 (m, 2H), 7.53 - 7.47 (m, 3H), 7.37 (t, J= 7.6 Hz, 1H), 7.17 (t, J= 3.6 Hz, 1H), 7.15 -7.07 (m, 2H), 5.89 (s, 1H), 5.60 (s, 1H), 5.48 (s, 1H), 3.47 (s, 3H), 2.55(s, 3H).

[1214] Example 181: (S)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide

[1215]

[1216] The title compound was the second peak from the chiral separation of 5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide (example 173) using conditions E (42.8% yield, RT=8.78min, second peak) as a white solid. LCMS(ESI) [M + H]+: 492.10. ’H NMR (400 MHz, Acetonitrile-d3) 5 7.76 - 7.66 (m, 2H), 7.54 - 7.46 (m, 3H), 7.38 (t, J = 7.6 Hz, 1H), 7.19 - 7.14 (m, 1H), 7.14 - 7.05 (m, 2H), 5.89 (s, 1H), 5.60 (d, J= 0.7 Hz, 1H), 5.48 (s, 1H), 3.46 (s, 3H), 2.55 (s, 3H).

[1217] Example 182: N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-5-(hydroxymethyl)thiophene-2-sulfonamide

[1218]

[1219] The title compound was obtained in analogy to Example 173. To a stirred solution of 5-[(benzyloxy)methyl]-N-{2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin- 3-yl}thiophene-2-sulfonamide (110 mg, 0.190 mmol, 1 equiv) in DCM (10 mL) was added Titanium(IV) chloride(1.0 M in dichloromethane) (0.07 mL, 0.380 mmol, 2 equiv) in portions at 0 oC under nitrogen atmosphere. The resulting mixture was stirred at room temperature overnight. Desired product could be detected by LCMS. The reaction was quenched by the addition of sat. NH4CI (aq.) (2 mL) at 0°C. The resulting mixture was extracted with CH2Q2 (3 x 10 mL). The combined organic layers were washed with brine (3 x 10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Prep-HPLC with the following conditions (Column: Xselect CSH Prep C18, 30*150mm 5pm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: isocratic 37% to 56% B in 10 min; Wave Length: 254 / 220 nm; RTl(min): 10.30 min) to afford N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-5-(hydroxymethyl)thiophene-2-sulfonamide (25.3 mg, 27.23% yield) as a white solid.

[1220] LCMS (ESIpos): m / z = 490.05 [M+H]+. 1H NMR (400 MHz, Acetonitrile-d3) δ 8.68 (s, 1H), 7.78 -7.74 (m, 1H), 7.69 (d, J = 7.4 Hz, 1H), 7.52 - 7.46 (m, 2H), 7.45 (d, J = 3.9 Hz, 1H), 7.38 (t, J = 7.7 Hz, 1H), 7.15 - 7.05 (m, 2H), 6.95 - 6.91 (m, 1H), 5.87 (s, 1H), 4.75 (d, J = 1.0 Hz, 2H), 3.77 (s, 1H), 3.46 (s, 3H), 2.55 (s, 3H).

[1221] Example 183: N-[8-(difluoromethyl)-2-[(S)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide

[1222]

[1223] a) N- { 8-[(benzyloxy)methyl] -2-[methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl } -4-methylbenzenesulfonamide

[1224] The title compound was obtained in analogy to Example 6 as a white solid (65.0% yield) using 3-amino-8-[(benzyloxy)methyl]-2-[methoxy(phenyl)methyl]quinazolin-4-one and p-toluene sulfonyl chloride.

[1225] b) N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide To a stirred solution of N-{8-[(benzyloxy)methyl]-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (880.0 mg, 1.584 mmol, 1.0 equiv) in DCM (10 mL) was added Titanium(IV) chloride (1.0 M in dichloromethane) (600.7 mg, 3.168 mmol, 2.0 equiv) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 h under nitrogen atmosphere. The reaction was quenched by the addition of sat. NH4CI (aq.) (40 mL) at 0 °C. The aqueous layer was extracted with EtOAc (3 x 40 mL). The combined organic layers dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH2C12 / MeOH (10:1) to afford N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (500.0 mg, 67.82% yield) as a yellow oil. LCMS (ESI) [M + H] +: 466.1.

[1226] c) A-{8-formyl-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide

[1227] To a stirred solution of A-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (Example 80, 490.0 mg, 1.053 mmol, 1.0 equiv) in DCM (50 mL) was added MnO2(915.0 mg, 10.530 mmol, 10.0 equiv) at room temperature under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 days under nitrogen atmosphere. The resulting mixture was filtered, the filter cake was washed with DCM (3 x 100 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH2Cl2 / MeOH (10:1) to afford A-{8-formyl-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (310.0 mg, 63.54% yield) as a yellow oil. LCMS (ESI) [M + H]+: 464.1.

[1228] d) N-[8-(difhioromethyl)-2-[(S)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide

[1229] To a stirred solution of A-{8-formyl-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-methylbenzenesulfonamide (290.0 mg, 0.626 mmol, 1.0 equiv) in DCM (5 mL) was added DAST (201.7 mg, 1.252 mmol, 2.0 equiv) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at 0 °C for overnight under nitrogen atmosphere. The reaction was quenched by the addition of sat. NH4CI (aq.) (5 mL) at 0 °C. The aqueous layer was extracted with EtOAc (3 x 10 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product (50 mg) was purified by Prep-HPLC with the following conditions (Column: CHIRAL ART Cellulose-SC, 3*25 cm, 5 pm; Mobile Phase A: Hex(0.1% FA)-HPLC, Mobile Phase B: EtOH; Flow rate: 40 mL / min; Gradient: isocratic 10; Wave Length: 200 / 228 nm; RTl(min): 7.024; RT2(min): 8.34; Sample Solvent: EtOH; Injection Volume: 0.6 mL; Number Of Runs: 4) to afford N-[8-(difluoromethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (30.0 mg, 9.88% yield) as a white solid. Chiral HPLC separation using conditions F afforded N-[8-(difluoromethyl)-2-[(S)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide as white solid (24.0% yield, RT=8.34min, second peak). LCMS (ESI) [M + H]+: 486.10. ’H NMR (400 MHz, Acetonitrile-d3) 58.13 - 8.05 (m, 1H), 8.02 - 7.95 (m, 1H), 7.72 - 7.41 (m, 6H), 7.39 - 7.31 (m, 5H), 5.86 (s, 1H), 3.44 (s, 3H), 2.43 (s, 3H).

[1230] Example 184 N-[8-(difluoromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide

[1231]

[1232] The title compound was the first peak from the chiral separation of N-[8-(difluoromethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide (example 183) using conditions F (27.0% yield, RT=7.0min, first peak) as a white solid. LCMS (ESI) [M + H]+: 486.10. ’H NMR (400 MHz, Acetonitrile-d3) 58.12 - 8.07 (m, 1H), 8.01 - 7.96 (m, 1H), 7.72 - 7.41 (m, 6H), 7.40 - 7.31 (m, 5H), 5.86 (s, 1H), 3.44 (s, 3H), 2.43 (s, 3H).

[1233] Example 185: N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide

[1234]

[1235] a) V-{8-chloro-6-fhioro-2-[(S)-(4-fhiorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide The title compound was obtained in analogy to example 6 as a white solid (42.7% yield) using 3-amino-8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)(methoxy)methyl]quinazolin -4-one and 4-iodobenzenesulfonyl chloride. LC-MS (ESI, m / z): [M-H]+: 618.

[1236] b) N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide

[1237] To a stirred solution of A-{8-chloro-6-fhioro-2-[(S)-(4-fhiorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide (140 mg, 0.22 mmol, 1.0 equiv), (15,35)-3-fluorocyclobutan -1 -amine hydrochloride (57 mg, 0.45 mmol, 2.0 equiv) and Cs2CO3(221 mg, 0.68 mmol, 3.0 equiv) in dioxane (2 mL) were added Pd2(dba)3 (21 mg, 0.023 mmol, 0.1 equiv) and Xantphos (26 mg, 0.045 mmol, 0.2 equiv) dropwise at room temperature under nitrogen atmosphere. The resulting mixture was stirred at 80 °C for overnight under nitrogen atmosphere. The reaction was quenched with water at room temperature. The resulting mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (3 x 40 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by re versed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, acetonitrile in Water (0.1% formic acid), 10% to 50% gradient in 30 min; detector, UV 254 nm. The crude product was purified by Prep-HPLC with the following conditions (Column: XBridge Prep OBD Cl 8 Column 30*150 mm, 5pm; Mobile Phase A: Water(0.1% formic acid), Mobile Phase B: acetonitrile; Flow rate: 60 mL / min mL / min; Gradient: 42% B to 59% B in 30 min; Wave Length: 254 / 220 nm; RTl(min): 14.14) to affordA-[8-chloro-6-fhioro-2-[(S)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide (20.1 mg, 15.32% yield) as a white solid. LC-MS (ESI, m / z): [M+ H]+: 579.10. ’H NMR (400 MHz, Acetonitrile-d3) δ 7.77 (dd, J = 8.5, 2.9 Hz, 1H), 7.58 - 7.32 (m, 5H), 7.15 - 6.99 (m, 2H), 6.58 - 6.40 (m, 2H), 5.90 (s, 1H), 5.61 (d, J= 6.6 Hz, 1H), 4.98 - 4.75 (m, 1H), 3.57 - 3.44 (m, 1H), 3.42 (s, 3H), 2.98 - 2.84 (m, 2H), 2.01 - 1.90 (m, 2H).

[1238] Example 186: 4-(l,l-difluoroethyl)-N-[8-(fluoromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide

[1239]

[1240] a) N- { 8-[(benzyloxy)methyl] -2-[methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl} -4-( 1, 1 -difluoroethyl)benzenesulfonamide

[1241] The title compound was obtained in analogy to example 6 as a white solid (56.1% yield) using 3-amino-8-[(benzyloxy)methyl]-2-[methoxy(phenyl)methyl]quinazolin-4-one and 4-(l,l-difluoroethyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 606.1.

[1242] b) 4-(l,l-difluoroethyl)-N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide

[1243] To a stirred solution of A-{8-[(benzyloxy)methyl]-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-4-(l,l-difluoroethyl)benzenesulfonamide (900.0 mg, 1.486 mmol, 1 equiv) in DCM (10 mL) was added Titanium(IV) chloride(1.0 M in dichloromethane) (563.6 mg, 2.972 mmol, 2.0 equiv) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at 0 °C for overnight under nitrogen atmosphere. The reaction was quenched by the addition of sat. NH4CI (aq.) (20 mL) at 0 °C. The aqueous layer was extracted with CH2Q2 (3 x 20 mL). dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH2Cl2 / MeOH (10:1) to afford 4-(l, 1-difluorocthyl )- / V- [8-(hydroxymethyl)-2- [methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl]benzenesulfonamide (150.0 mg, 19.58% ) as a yellow solid. LCMS (ESI) [M + H]+: 516.1.

[1244] c) 4-(l,l-difhioroethyl)-N-[8-(fhioromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide

[1245] To a stirred solution of 4-(l,l-difhioroethyl)-A-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide (145.0 mg, 0.281 mmol, 1.0 equiv) in DCM (2 mL) was added DAST (90.6 mg, 0.562 mmol, 2.0 equiv) at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 h under nitrogen atmosphere. The reaction was quenched by the addition of sat. NH4CI (aq.) (5 mL) at 0 °C. The aqueous layer was extracted with CH2Q2 (3 x 10 mL). dried over anhydrous Na2SO4E. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, MeCN in Water (0.1% FA), 0% to 60% gradient in 10 min; UV 254 nm. to afford 4-(l,l-difluoroethyl)-N-[8-(fluoromethyl)-2-[methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide (100.0 mg, 68.70% ) as a white solid. Chiral HPLC separation using conditions E afforded 4-( 1, 1-difhioroethyl)-N-[8-(fhioromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide (41.4% yield, RT=11.6min, first peak) as a white solid.

[1246] Example 187: N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide

[1247]

[1248] The title compound was obtained in analogy to Example 185 as a white solid (11.1% yield) using A-{8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4-iodobenzenesulfonamide and (ls,3s)-3-fhiorocyclobutan-l-amine hydrochloride. LC-MS (ESI, m / z): [M+ H]+: 579.15.!H NMR (400 MHz, Acetonitrile-d3) δ 7.77 (dd, J = 8.5, 2.9 Hz, 1H), 7.58 - 7.32 (m, 5H), 7.15 - 6.99 (m, 2H), 6.58 - 6.40 (m, 2H), 5.90 (s, 1H), 5.61 (d, J= 6.6 Hz, 1H), 4.98 - 4.75 (m, 1H), 3.57 - 3.42 (m, 4H), 2.98 - 2.84 (m, 2H), 2.01 - 1.90 (m, 2H).

[1249] Example 188: (R)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide

[1250]

[1251] N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide was obtained in analogy to Example 6 as a white solid (45.4% yield) using 3-amino-2-[(4-fluorophenyl)(methoxy)methyl]-8-methoxyquinazolin-4-one and p-toluenesulfonyl chloride. Chiral separation using conditions H afforded (R)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide (42.9% yield, RT=3.12min, first peak) as a white solid. LCMS (ESI) [M + H]+: 484.10. ’H NMR (400 MHz, DMSO-d6) 5 11.74 - 11.21 (m, 1H), 7.67 (d, J= 7.9 Hz, 2H), 7.52 - 7.32 (m, 7H), 7.28 - 7.12 (m, 2H), 5.91 - 5.74 (m, 1H), 4.04 - 3.70 (m, 3H), 3.35 (s, 3H), 2.41 (s, 3H).

[1252] Example 189: (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fluoromethyl)thiophene-2-sulfonamide

[1253] F

[1254]

[1255] N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fhiorornethyl)thiophene-2-sulfonamide was obtained in analogy to Example 173 as a white solid (29.9% yield) using A-{8-chloro-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-5-(hydroxymethyl)thiophene-2-sulfonamide and DAST. Chiral separation using conditions F afforded (R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fhioromethyl)thiophene-2-sulfonamide (38.2% yield, RT=8.79min, first peak) as a white solid. LCMS(ESI) [M + H]+: 530.05.1H NMR (400 MHz, Acetonitrile-d3) 69.25 - 8.45 (m, 1H), 7.82 - 7.77 (m, 1H), 7.58 - 7.46 (m, 4H), 7.17 (t, J= 3.6 Hz, 1H), 7.16 - 7.07 (m, 2H), 5.88 (s, 1H), 5.61 (s, 1H), 5.49 (s, 1H), 3.46 (s, 3H).

[1256] Example 190: (S)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fluoromethyl)thiophene-2-sulfonamide F

[1257]

[1258] The title compound was the second peak from the chiral separation of N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(fhioromethyl)thiophene-2-sulfonamide (Example 189) using conditions F (32.8% yield, RT=14.31min, second peak) as a white solid. LCMS(ESI) [M + H]+: 530.05.1H NMR (400 MHz, Acetonitrile-d3) 59.25 - 8.45 (m, 1H), 7.79 (dd, J= 8.4, 2.9 Hz, 1H), 7.57 -7.44 (m, 4H), 7.20 - 7.15 (m, 1H), 7.14 - 7.05 (m, 2H), 5.88 (s, 1H), 5.61 (s, 1H), 5.49 (s, 1H), 3.46 (s, 3H).

[1259] Example 191: (S)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[1260]

[1261] 4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide was obtained in analogy to Example 23 as a white solid (15.4% yield) using 5-fhioro-2-[2-(4-fhiorophenyl)-2-methoxyacetamido]-3-methoxybenzoic acid and bis(7V'- { 4-[(difluoromethoxy)methyl]benzenesulfonyl } tert-butoxycarbohydraz ide). Chiral separation using conditions F afforded (S)-4-((difhioromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide (39.8% yield, RT=16.74min, second peak) as a white solid. LCMS (ESI) [M + H]+: 568.10. ’H NMR (400 MHz, Acetonitrile-d3) δ 7.79 (d, J= 8.4 Hz, 2H), 7.51 (d, J= 8.3 Hz, 2H), 7.42 (dd, J= 8.6, 5.6 Hz, 2H), 7.18 - 7.02 (m, 4H), 6.50 (t, J = 75.0 Hz, 1H), 5.85 (s, 1H), 5.00 (s, 2H), 3.97 (s, 3H), 3.40 (d, J= 0.7 Hz, 3H).

[1262] Example 192: N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-3,5-dimethyl-thiophene-2-sulfonamide

[1263] o=s=o o

[1264]

[1265] The title compound was obtained in analogy to Example 6 as a white solid (7.8% yield) using 3-amino-2-[(R)-(4-fluorophenyl)(methoxy)methyl]-8-methoxyquinazolin-4-one and 3, 5-dimethylthiophene-2- sulfonyl chloride. LCMS (ESI) [M + H]+: 504.15. ’H NMR (400 MHz, Acetonitrile-d3) 67.53 - 7.28 (m, 5H), 7.09 (t, J= 8.9 Hz, 2H), 6.69 (s, 1H), 5.93 (s, 1H), 3.96 (s, 3H), 3.42 (s, 3H), 2.37 (s, 3H), 2.25 (s, 3H).

[1266] Example 193: N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-2-methyl-thiazole-5-sulfonamide

[1267] F

[1268]

[1269] The title compound was obtained in analogy to Example 6 as a white solid (25.2% yield) using 3-amino-2-[(R)-(4-fluorophenyl)(methoxy)methyl]-8-methoxyquinazolin-4-one and 2-methyl-l,3-thiazole-5-sulfonyl chloride. LCMS (ESI) [M + H]+: 491.15. ’H NMR (400 MHz, DMSO-d6) 5 11.86 (s, 1H), 8.03 (s, 1H), 7.56 -7.39 (m, 5H), 7.27 - 7.04 (m, 2H), 5.86 (s, 1H), 3.94 (d, J= 15.3 Hz, 3H), 3.38 (s, 3H), 2.75 (s, 3H).

[1270] Example 194: 5-(l-fluorocyclopropyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]thiophene-2-sulfonamide o=s=o o

[1271]

[1272] a) N- { 6-fluoro-2- | ( / ?)-mcthoxy(phcnyl )mcthyl | -4-oxoquinazolin-3-yl } -5-( 1 -hydroxycyclopropyl)thiophene-2-sulfonamide

[1273] The title compound was obtained in analogy to Example 6 as a white solid (28.6% yield) using 3-amino-6-fhioro-2-[(R)-methoxy(phenyl)methyl] quinazolin-4-one and 5-(l-hydroxycyclopropyl) thiophene-2- sulfonyl chloride. LC-MS (ESI, m / z): [M + H]+: 502.00

[1274] b) 5-(l-fluorocyclopropyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3 -yl] thiophene-2- sulfonamide

[1275] To a stirred solution of A-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-5-(l -hydroxycyclopropyl) thiophene-2- sulfonamide (100 mg, 0.199 mmol, 1 equiv) in DCM (1 mL) was added diethylamino sulfur trifluoride (64.3 mg, 0.398 mmol, 2 equiv) dropwise at -78 °C under nitrogen atmosphere. The resulting mixture was stirred at -78 °C for 30 min under nitrogen atmosphere. The reaction was quenched with sat. NH4CI (aq.) at -78 °C. The resulting mixture was extracted with CH2Cl2(3 x 10 mL). The combined organic layers were washed with water (3 x 5 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product (60 mg) was purified by Prep-HPLC to afford A-{6-fhioro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}-5-(l-fluorocyclopropyl)thiophene-2-sulfonamide (13.5 mg, 13.45% yield) as a white solid. LC-MS (ESI, m / z): [M - H]": 502.00.1H NMR (400 MHz, DMSO-ds) 6 11.80 (s, 1H), 7.92 (s,lH), 7.78 (s, 1H), 7.66 (s, 1H), 7.56 (s, 1H), 7.37 (d, J = 19.1 Hz, 5H), 7.08 (d, J = 4.0 Hz, 1H), 5.83 (s, 1H), 3.37 (s, 3H), 1.63 (d, J= 18.6 Hz, 2H), 1.31 - 1.22 (m, 2H).

[1276] Example 195: 4-(l-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1277]

[1278] The title compound was obtained in analogy to Example 6 as a white solid (69.1% yield) using 3-amino-2-[(7?)-(4-fluorophenyl)(methoxy)methyl]-8-methoxyquinazolin-4-one and 4-(l-fhiorocyclopropyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 528.15.!H NMR (400 MHz, Acetonitrile-d3) 68.63 (s, 1H), 7.86 - 7.69 (m, 2H), 7.49 - 7.28 (m, 7H), 7.09 (t, J= 8.9 Hz, 2H), 5.86 (s, 1H), 3.96 (s, 3H), 3.42 (s, 3H), 1.63 - 1.54 (m, 2H), 1.30 - 1.10 (m, 2H).

[1279] Example 196: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy- methyl]quinazolin-3-yl]-5-(difluoromethyl)thiophene-2-sulfonamide

[1280]

[1281] a) A-{8-chloro-6-fhioro-2-[(4-fhiorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-5- formylthiophene-2- sulfonamide

[1282] A solution of A-{8-chloro-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4- oxoquinazolin-3-yl}-5-(hydroxymethyl)thiophene-2-sulfonamide (prepared in analogy to example 189, 300 mg, 0.568 mmol, 1 equiv) and MnO2(495.0 mg, 5.694 mmol, 10.02 equiv) in DCM (20 mL) was stirred at room temperature for 12 h under nitrogen atmosphere. The resulting mixture was filtered, the filter cake was washed with DCM (20 mL) (3 x 20 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with CH2Cl2 / MeOH (10:1) to afford A-{8-chloro-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-5- formylthiophene-2- sulfonamide (200 mg, 66.92% yield) as a white solid. MS (ESIpos): m / z = 526.00 [M+H]+. b) N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(difluoromethyl)thiophene-2- sulfonamide

[1283] To a stirred solution of A-{8-chloro-6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-5-formylthiophene-2-sulfonamide (200 mg, 0.380 mmol, 1 equiv) in DCM (10 mL) was added DAST (0.84 mL, 0.840 mmol, 2.21 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at 0 °C for additional 1 h. Desired product could be detected by LCMS. The reaction was quenched with sat. NH4CI (aq.) at 0 °C. The resulting mixture was extracted with CH2Cl2(3 x 10 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by Prep-HPLC with the following conditions (Column: Xbridge Phenyl OBD Column, 30* 150mm 5pm; Mobile Phase A: Water (0.1%FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 45% B to 62% B in 30 min; Wave Length: 254 / 220 nm; RT=10.08min) to afford N-[8-chloro-6-fluoro-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(difhioromethyl)thiophene-2-sulfonamide (51.9 mg, 24.91% yield) as a white solid. Chiral separation using conditions J afforded N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(difluoromethyl)thiophene-2-sulfonamide (32.0% yield, RT=3.82min, first peak) as a white solid. LCMS(ESI) [M + H]+: 548.05.1H NMR (400 MHz, Acetonitrile-d3) δ 7.82 (dd, J = 8.4, 2.9 Hz, 1H), 7.62 -7.49 (m, 4H), 7.42 - 7.37 (m, 1H), 7.22 - 6.93 (m, 3H), 5.92 (s, 1H), 3.49 (d, J = 1.0 Hz, 3H).

[1284] Example 197: 5-(l-chlorocyclopropyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]thiophene-2-sulfonamide

[1285]

[1286] The title compound was obtained in analogy to Example 87 as a white solid (5.6% yield) using 3-amino-6-fhioro-2-[(R)-methoxy(phenyl)methyl] quinazolin-4-one and 5-(l-chlorocyclopropyl)thiophene-2-sulfonyl chloride. LC-MS (ESI, m / z): [M + H]+: 520.10. 'HNMR (400 MHz, DMSO-d6) 8 11.80 (s, 1H), 7.92 (s, 1H), 7.82 - 7.73 (s, 1H)7.66 (s, 1H), 7.56 (s, 1H), 7.37 (d, J= 19.1 Hz, 5H), 7.08 (d, J= 4.0 Hz, 1H), 5.83 (s, 1H), 3.37 (s, 3H), 1.63 (d, J= 18.6 Hz, 2H), 1.33 - 1.21 (m, 2H).

[1287] Example 198: N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5- [(E)-3-fluoroprop-l-enyl]thiophene-2-sulfonamide

[1288]

[1289] To a stirred solution of A-{6-fluoro-2-[(R)-methoxy(phenyl) methyl] -4-oxoquinazolin-3-yl}-5-(l -hydroxycyclopropyl) thiophene-2- sulfonamide (prepared by analogy to example 194. 100 mg, 0.199 mmol, 1 equiv) in DCM (1.0 mL) was added DAST (64.3 mg, 0.398 mmol, 2 equiv) dropwise at -78 °C under nitrogen atmosphere. The resulting mixture was stirred at -78 °C for 1 h under nitrogen atmosphere. The reaction was poured into sat. NH4CI (aq.) at -78 °C, the resulting mixture was extracted with CH2Cl2(3 x 5 mL). The combined organic layers were washed with water (3 x 5 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product (60 mg) was purified by Prep-HPLC with the following conditions (Column:

[1290] Xselect CSH Prep C18, 30*150mm 5pm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: isocratic 42% to 57% B in 14 min; Wave Length: 254 / 220 nm; RT=12.65 min) to afford N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-[(E)-3-fluoroprop-l-enyl]thiophene-2-sulfonamide (11.7 mg, 11.65% yield) as a white solid. LC-MS (ESI, m / z): [M - H]:

[1291] 502.05. ’H NMR (400 MHz, DMSO-d6) 8 11.80 (s, 1H), 7.91 (s, 1H), 7.77 (s, 1H), 7.65 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.40 (s, 3H), 7.38 - 7.32 (m, 1H), 7.29 (s, 1H), 5.83 (d, J = 13.5 Hz, 2H), 5.57 (s, 1H), 5.34 (s, 1H), 5.23 (s, 1H), 3.36 (s, 3H).

[1292] Example 199: 4-[(3,3-difluorocyclobutyl)amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1293]

[1294] 4-[(3,3-difhiorocyclobutyl)amino]-N-[6,8-difhioro-4-oxo-2-[(4-fluorophenyl)-methoxy- methyl]quinazolin-3-yl]benzenesulfonamide was obtained in analogy to Example 104 as a white solid (41.4% yield) using A-{6,8-difhioro-2-[(4-fhiorophenyl)(methoxy)methyl]-4- oxoquinazolin-3-yl}-4- iodobenzenesulfonamide and 3,3-difluorocyclobutan-l-amine hydrochloride. Chiral separation using conditions E afforded 4-[(3,3- difhiorocyclobutyl)amino]-N-[6,8-difhioro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy- methyl]quinazolin-3-yl]benzenesulfonamide (42.6% yield, RT=18.66min, second peak) as a white solid. LCMS (ESI) [M + H]+: 581.20. ’H NMR (400 MHz, Acetonitrile-d3) 68.50 (s, 1H), 7.55 - 7.32 (m, 6H), 7.09 (t, J= 8.9 Hz, 2H), 6.61 - 6.43 (m, 2H), 5.89 (s, 1H), 5.70 (d, J = 5.8 Hz, 1H), 3.93 - 3.76 (m, 1H), 3.41 (s, 3H), 3.15 - 2.93 (m, 2H), 2.58 - 2.40 (m, 2H).

[1295] Example 200: N-[8-chloro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin- 3-yl] -4- ( 1 -fluorocyclopropyl)benzenesulfonamide

[1296]

[1297] N-[8-chloro-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l- fluorocyclopropyl)benzenesulfonamide was obtained in analogy to Example 23 as a white solid (21.3% yield) using 3-chloro-2-[2-(4-fhiorophenyl)-2-methoxyacetamido]benzoic acid and A'-[4-(l-fluorocyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. Chiral separation using conditions E afforded N-[8-chloro-4-oxo-2-[(R)-(4-fluorophenyl)- methoxy-methyl]quinazolin-3-yl] -4-( 1 -fluorocyclopropyl)benzenesulfonamide (28.1 % yield, RT=19.74min, first peak) as a white solid. LCMS (ESI) [M + H]+: 532.09.1H NMR (400 MHz, DMSO-76) 6 11.54 (s, 1H), 8.03 (s, 1H), 7.82 (dd, 7= 21.2, 8.2 Hz, 3H), 7.59 -7.36 (m, 5H), 7.22 (t, 7= 8.6 Hz, 2H), 5.85 (s, 1H), 3.53 (s, 3H) 1.68 - 1.55 (m, 2H), 1.33 - 1.24 (m, 2H).

[1298] Example 201: 4-(l-cyanocyclopropyl)-N-[8-(2,2-difluoroethoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1299] F

[1300] o=s=oo

[1301]

[1302] 4-(l-cyanocyclopropyl)-N-[8-(2,2-difluoroethoxy)-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide was obtained in analogy to Example 6 as a white solid (38.9% yield) using 3-amino-8-(2,2-difluoroethoxy)-2-[(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l-cyanocyclopropyl)benzenesulfonyl chloride. Chiral separation using conditions K afforded 4-(l-cyanocyclopropyl)-N-[8-(2,2-difluoroethoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide (43.7% yield, RT=11.18min, first peak) as a white solid. LCMS (ESI) [M+H]+: 584.13.!H NMR (400 MHz, Acetonitrile-d3) δ 7.77 (d, 7= 8.3 Hz, 2H), 7.54 - 7.35 (m, 7H), 7.11 (t, J = 8.9 Hz, 2H), 6.46 - 6.08 (m, 1H), 5.88 (s, 1H), 4.40 (t, J = 13.9 Hz, 2H), 3.43 (d, 7= 0.8 Hz, 3H), 1.88 - 1.81 (m, 2H), 1.56 - 1.49 (m, 2H).

[1303] Example 202: 4-(l-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1304]

[1305] 4-(l-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(4-fluorophenyl)-methoxy- methyl]quinazolin-3-yl]benzenesulfonamide was obtained in analogy to Example 23 as a yellow solid (18.8% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]-3- methylbenzoic acid and A^'-[4-(l-cyanocyclopropyl)benzenesulfonyl] tertbutoxycarbohydrazide. Chiral separation using conditions E afforded 4-(l- cyanocyclopropyl)-N-[6-fhioro-8-methyl-4-oxo-2-[(S)-(4-fluorophenyl)-rnethoxy- methyl]quinazolin-3-yl]benzenesulfonamide (27.8% yield, RT=9.07min, first peak) as a white solid. LCMS (ESI) [M + H]+: 537.14. ’H NMR (400 MHz, DMSO-d6) 811.73 (d, J = 179.4 Hz, 1H), 7.84 - 7.76 (m, 2H), 7.75 - 7.60 (m, 1H), 7.54 - 7.49 (m, 2H), 7.49 - 7.35 (m, 3H), 7.22 (s, 2H), 5.82 (s, 1H), 3.35 (s, 3H), 2.64 (s, 2H), 2.29 (s, 1H), 1.92 (q, J = 3.7 Hz, 2H), 1.64 (q, J= 4.6 Hz, 2H).

[1306] Example 203: 4-(l-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)- methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1307]

[1308] 4-(l-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(4-fluorophenyl)-methoxy- methyl]quinazolin-3-yl]benzenesulfonamide was obtained in analogy to Example 23 as a yellow solid (29.3% yield) using 3,5-difhioro-2-[2-(4-fhiorophenyl)-2- methoxyacetamido]benzoic acid and tert-butyl 2-((4-(l- cyanocyclopropyl)phenyl)sulfonyl)hydrazine-l-carboxylate. Chiral separation using conditions E afforded 4-(l-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(S)-(4- fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide (40.8% yield, RT=9.31min, first peak) as a white solid. LCMS (ESI) [M + H]+: 541.10. ’H NMR (400 MHz, Acetonitrile-d3) δ 7.94 – 7.66 (m, 2H), 7.58 - 7.45 (m, 5H), 7.41 - 7.28 (m, 1H), 7.20 - 7.03 (m, 2H), 5.88 (s, 1H), 3.45 (s, 3H), 1.91 - 1.84 (m, 2H), 1.60 - 1.53 (m, 2H).

[1309] Example 204: 4-(l-cyanocyclopropyl)-N-[8-(cyclopropoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1310] F

[1311] o=s=o o

[1312]

[1313] 4-(l-cyanocyclopropyl)-N-[8-(cyclopropoxy)-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide was obtained in analogy to Example 6 as a white solid (41.2% yield) using 3-amino-8-cyclopropoxy-2-[(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l-cyanocyclopropyl)benzenesulfonyl chloride. Chiral separation using conditions K afforded 4-(l-cyanocyclopropyl)-N-[8-(cyclopropoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide (42.0% yield, RT=7.12min, first peak) as a white solid. LCMS(ESI) [M + H]+: 561.15. ’H NMR (400 MHz, DMSO-d6) 8 11.43 (s, 1H), 7.82 - 7.63 (m, 3H), 7.62 - 7.27 (m, 6H), 7.20 (s, 2H), 5.80 (s, 1H), 4.00 (d, J = 44.7 Hz, 1H), 3.36 - 3.33 (m, 3H), 1.91 (d, J = 2.8 Hz, 2H), 1.63 (s, 2H), 0.99 - 0.54 (m, 4H).

[1314] Example 205: 4-(l-cya >cyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1315]

[1316] The title compound was the second peak from the chiral separation of 4-(l- cyanocyclopropyl)-N-[6,8-difhioro-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide (Example 203) using conditions E (40.8% yield, RT=16.32min, second peak) as a white solid. LCMS (ESI) [M + H]+: 541.10. ’H NMR (400 MHz, Acetonitrile-d3) 67.92 - 7.66 (m, 2H), 7.60 - 7.41 (m, 5H), 7.38 (m, J = 2.9, 1.6 Hz, 1H), 7.18 - 7.05 (m, 2H), 5.88 (s, 1H), 3.45 (s, 3H), 1.93 - 1.80 (m, 2H), 1.66 - 1.51 (m, 2H).

[1317] Example 206: 4-(l-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1318]

[1319] The title compound was the second peak from the chiral separation of 4-(l-cyanocyclopropyl)-N-[6-fhioro-8-methyl-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide (Example 202) using conditions E (28.6% yield, RT=12.65min, second peak) as a white solid. LCMS (ESI) [M + H]+: 537.14.!H NMR (400 MHz, DMSO-d6) 8 11.54 (s, 1H), 7.85 - 7.75 (m, 2H), 7.66 (s, 1H), 7.53 - 7.48 (m, 2H), 7.48 - 7.37 (m, 3H), 7.21 (s, 2H), 5.83 (s, 1H), 3.33 (s, 3H), 2.62 (s, 2H), 2.27 (s, 1H), 1.95 - 1.83 (m, 2H), 1.63 (q, J= 4.7 Hz, 2H).

[1320] Example 207: 5-(hydroxymethyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide

[1321]

[1322] The title compound was obtained by chiral separation of N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-5-(hydroxymethyl)thiophene-2-sulfonamide (example 182) using conditions L (33.4% yield, RT=23.62min, second peak) as a white solid. LCMS (ESI) [M+H]+: 490.0. ’H NMR (400 MHz, Acetonitrile-d3) 67.79 (d, J= 8.0 Hz, 1H), 7.72 (d, J= 7.3 Hz, 1H), 7.56 - 7.46 (m, 3H), 7.41 (t, J= 7.7 Hz, 1H), 7.13 (t, J= 8.8 Hz, 2H), 6.97 (dt, J= 3.9, 1.1 Hz, 1H), 5.90 (s, 1H), 4.78 (d, J= 1.0 Hz, 2H), 3.71 (d, J= 42.5 Hz, 1H), 3.48 (s, 3H), 2.58 (s, 3H). Example 208: 5-(hydroxymethyl)-N-[6-fluoro-8-methyl -4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide

[1323]

[1324] a) [5-({6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl } sulfamoyl)thiophen-2-yl] methyl acetate

[1325] The title compound was obtained in analogy to Example 23 as a yellow solid (48.8% yield) using 5-fluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]-3-methylbenzoic acid and (5-{[(tert-butoxycarbonyl)amino]aminosulfonyl]thiophen-2-yl)methyl acetate. LCMS (ESI) [M + H]+: 550.09.

[1326] b) 5-(hydroxymethyl)-N-[6-fluoro-8-methyl -4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide

[1327] To a stirred mixture of [5-({6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl]sulfamoyl)thiophen-2-yl]methyl acetate (200 mg, 0.364 mmol, 1 equiv) and H2O (4 mL) in THF (4 mL) were added LiOH (33.9 mg, 1.415 mmol, 3.89 equiv)in portions at room temperature. The resulting mixture was stirred at room temperature for 30 min. The mixture was acidified to pH 6 with cone. HC1. The resulting mixture was extracted with EtOAc (3 x 50 mL). The combined organic layers were washed with brine (1 x 80 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product (300 mg) was purified by Prep-HPLC with the following conditions (Column: XSelect CSH Fluoro Phenyl 30*150 mm, 5pm; Mobile Phase A: Water (0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient: 33% B to 50% B in 30 min; Wave Length: 254 / 220 nm; RT= 11.42 min) to afford A-{6-fluoro-2-[(4-fluorophenyl)(methoxy)methyl]-8-methyl-4-oxoquinazolin-3-yl]-5-(hydroxymethyl)thiophene-2-sulfonamide (150 mg, 81.21% yield) as a white solid. Chiral separation using conditions E afforded NAME (62.7% yield, RT=14.92min, first peak) as a white solid. LCMS (ESI) [M + H]+: 508.08.1H NMR (400 MHz, DMSO-d6) 6 11.77 (d, J= 190.2 Hz, 1H), 7.70 (s, 1H), 7.54 - 7.37 (m, 4H), 7.20 (s, 2H), 7.02 - 6.98 (m, 1H), 5.89 - 5.73 (m, 2H), 4.71 (d, J= 5.1 Hz, 2H), 3.34 (s, 3H), 2.65 (s, 2H), 2.28 (s, 1H).

[1328] Example 209: (R)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide

[1329]

[1330] The title compound was the second peak from the chiral separation of 4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide (Example 191) using conditions E (43.8% yield, RT=14.58min, first peak) as a white solid. LCMS (ESI) [M + H]+: 568.10.1H NMR (400 MHz, Acetonitrile-d3) δ 7.79 (d, J= 8.4 Hz, 2H), 7.51 (d, J= 8.3 Hz, 2H), 7.42 (dd, J = 8.6, 5.6 Hz, 2H), 7.18 - 7.02 (m, 4H), 6.50 (t, J = 75.0 Hz, 1H), 5.85 (s, 1H), 5.00 (s, 2H), 3.97 (s, 3H), 3.40 (d, J = 0.7 Hz, 3H).

[1331] Example 210: 5-(l-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide F

[1332]

[1333] a) N- { 2-[(4-fluorophenyl)(methoxy)methyl] -8-methoxy-4-oxoquinazolin-3-yl } -5-( 1 -hydroxycyclopropyl)thiophene-2-sulfonamide

[1334] The title compound was obtained in analogy to Example 6 as a white solid (51.6% yield) using 3-amino-2-[(4-fluorophenyl)(methoxy)methyl]-8-methoxyquinazolin-4-one and 5-(l-hydroxycyclopropyl)thiophene-2-sulfonyl chloride. LCMS (ESI) [M + H]+: 532.05

[1335] b) 5-(l-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide

[1336] To a stirred solution of N-{2-[(4-fluorophenyl)(methoxy)methyl]-8-methoxy-4-oxoquinazolin-3-yl}-5-(l-hydroxycyclopropyl)thiophene-2-sulfonamide (330 mg, 0.621 mmol, 1 equiv) in DCM (4 mL) was added DAST (300.2 mg, 1.863 mmol, 3 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at 0 °C for 2 h under nitrogen atmosphere. The reaction was quenched with sat. NH4C1 (aq.) at 0 °C. The resulting mixture was extracted with EtOAc (2 x 3 mL). The combined organic layers were washed with water (2 x 3 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue product was purified by reverse phase flash with the following conditions (Column: Xselect CSH Prep C18, 30*150mm 5 U m; Mobile Phase A: Water (0.1% FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient (B%): isocratic 41% to 60% B in 12 min; Wave Length: 254 / 220 nm; RT=11.08 min) to afford 5-(l-fhiorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide (79.2 mg, 23.91% yield) as a white solid. Chiral separation using conditions F afforded 5-(l-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide (40.2% yield, RT=5.82min, first peak) as a white solid. LCMS (ESI) [M + H]+: 534.10. 1H NMR (400 MHz, Acetonitrile-d3) δ 8.91 (s, 1H), 7.64 - 7.43 (m, 5H), 7.43 - 7.35 (m, 1H), 7.12 (t, J = 8.7 Hz, 2H), 6.95 (d, J = 3.9 Hz, 1H), 5.92 (s, 1H), 4.00 (s, 3H), 3.46 (s, 3H), 1.68 - 1.53 (m, 2H), 1.27 - 1.13 (m, 2H). Example 211: N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(l-fluorocyclopropyl)thiophene-2-sulfonamide

[1337] F

[1338]

[1339] The title compound was obtained in analogy to example 173 as a white solid (49.81% yield) using N-{6,8-difluoro-2-[(4-fluorophenyl) (methoxy) methyl]-4-oxoquinazolin-3-yl}-5-(l -hydroxycyclopropyl) thiophene-2- sulfonamide and DAST. Chiral separation using conditions M afforded N-[6,8-difhioro-4-oxo-2-[(R)-(4-fhiorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(l-fhiorocyclopropyl)thiophene-2-sulfonamide (28.0% yield, RT=17.6min, second peak) as a white solid. LC-MS (ESI, m / z): [M + H]+: 540.00. 1H NMR (400 MHz, DMSO-d6) 5 11.87 (s, 1H), 7.92 (s, 1H), 7.60 - 7.49 (m, 2H), 7.44 (dd, J = 8.4, 5.5 Hz, 2H), 7.21 (t, J = 8.7 Hz, 2H), 7.08 (dd, J = 4.0, 1.4 Hz, 1H), 5.83 (s, 1H), 3.37 (s, 3H), 1.70 - 1.56 (m, 2H), 1.33 - 1.21 (m, 2H).

[1340] Example 212: 5-(l-hydroxycyclopropyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide

[1341] F

[1342]

[1343] The title compound was obtained in analogy to example 156 as a white solid (34.7% yield) using 3-amino-2-[(4-fhiorophenyl)(methoxy)methyl]-8-methylquinazolin-4-one and 5-(l-hydroxycyclopropyl)thiophene-2-sulfonyl chloride. Chiral separation using conditions F afforded 5-(l-hydroxycyclopropyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide (22.1% yield, RT=8.95min, first peak) as a white solid. LCMS (ESI) [M + H]+: 516.11. 1H NMR (400 MHz, DMSO-d6) 5 11.65 (d, J = 188.1 Hz, 1H), 7.83 - 7.63 (m, 2H), 7.55 - 7.36 (m, 4H), 7.19 (t, J = 8.5 Hz, 2H), 6.80 (s, 1H), 6.71 (d, J = 4.0 Hz, 1H), 5.80 (d, J = 24.4 Hz, 1H), 3.39 (s, 3H), 2.64 (s, 2H), 2.26 (s, 1H), 1.28 (p, J = 5.1, 4.6 Hz, 2H), 1.08 (t, J = 3.9 Hz, 2H).

[1344] Example 213: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(hydroxymethyl)thiophene-2-sulfonamide

[1345] F

[1346]

[1347] a) 5-[(benzyloxy)methyl]-A-{8-chloro-6-fhioro-2-[(R)-(4-fhiorophenyl)(methoxy)methyl]- 4-oxoquinazolin- 3 -yl } thiophene -2- sulfonamide

[1348] The title compound was obtained in analogy to example 156 as an off-white oil (74.0% yield) using 3-amino-8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 5-[(benzyloxy)methyl]thiophene-2-sulfonyl chloride. LCMS (ESI) [M + H]+: 351.90.

[1349] b) N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]- 5-(hydroxymethyl)thiophene-2-sulfonamide

[1350] To a stirred solution of 5-[(benzyloxy)methyl]-N-{8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}thiophene-2-sulfonamide (120 mg, 0.194 mmol, 1 equiv) in DCM (15 mg) was added Titanium tetrachloride (0.78 mL, 0.776 mmol, 4 equiv) dropwise at 0 °C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for overnight under nitrogen atmosphere. The reaction was quenched with sat. sodium hyposulfite (aq.) at room temperature. The resulting mixture was extracted with CH2C12 (2 x 3 mL). The combined organic layers were washed with water (2 x 3 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by reverse phase flash with the following conditions (Column: XSelect CSH Fluoro Phenyl 30*150 mm, 5pm; Mobile Phase A: Water (0.1%FA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient (B%): 32% B to 49% B in 30 min; Wave Length: 254 / 220 nm; RT=10.02 min) to afford N-[8-chloro-6-fhioro-4-oxo-2-[(R)-(4-fhiorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(hydroxymethyl)thiophene-2-sulfonamide (14.3 mg, 13.95% yield) as a white solid. LCMS (ESI) [M + H]+: 528.00. 1H NMR (400 MHz, Acetonitrile-d3) δ 8.83 (s, 1H), 7.70 (d, J = 8.3 Hz, 1H), 7.59 - 7.43 (m, 1H), 7.42 - 7.27 (m, 3H), 7.02 (t, J = 8.7 Hz, 2H), 6.86 (d, J = 3.9 Hz, 1H), 5.77 (s, 1H), 4.67 (s, 2H), 3.76 (s, 1H), 3.36 (s, 3H).

[1351] Example 214: N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonamide

[1352]

[1353] 'CN

[1354] a) (lR,2R)-2-(4-bromophenyl)cyclopropane-l-carbonitrile

[1355] A solution of 4-bromostyrene (1 g, 5.46 mmol, 1 equiv), aminoacetonitrile hydrochloride (1.01 g, 10.926 mmol, 2 equiv), Fe(TPP)Cl (0.12 g, 0.164 mmol, 0.03 equiv) and NaNO2 (1.13 g, 16.389 mmol, 3 equiv) in H2O (10 mL) was stirred at room temperature for 12 h under nitrogen atmosphere. TLC find new point (PE / EA 10:1 Rf=0.5). The reaction was quenched with water at 0 oC. The resulting mixture was extracted with EtOAc (2 x 200 mL). The combined organic layers were washed with water (2 x 100 mL), dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (10: 1) to afford (lR,2R)-2-(4-bromophenyl)cyclopropane-l-carbonitrile (0.7 g, 57.70% yield) as a grey solid.

[1356] b) (lR,2R)-2-[4-(benzylsulfanyl)phenyl]cyclopropane-l-carbonitrile

[1357] A solution of (lR,2R)-2-(4-bromophenyl)cyclopropane-l-carbonitrile (0.3 g, 1.351 mmol, 1 equiv), benzyl mercaptan (0.20 g, 1.621 mmol, 1.2 equiv), Pd2(dba)3 (0.12 g, 0.135 mmol, 0.1 equiv), Xantphos (0.16 g, 0.270 mmol, 0.2 equiv) and DIPEA (0.52 g, 4.053 mmol, 3 equiv) in dioxane (5 mL) was stirred at 100 oC for 2 h under nitrogen atmosphere. TLC find new point (PE / EA 8:1 Rf=0.6). The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (8:1) to afford (lR,2R)-2-[4-(benzylsulfanyl)phenyl] cyclopropane- 1 -carbonitrile (0.35 g, 97.64% yield) as a yellow solid.

[1358] c) 4-[(lR,2R)-2-cyanocyclopropyl]benzenesulfonyl chloride

[1359] A solution of (lR,2R)-2-[4-(benzylsulfanyl)phenyl]cyclopropane-l-carbonitrile (300 mg, 1.130 mmol, 1 equiv), NCS (452.9 mg, 3.390 mmol, 3 equiv) and H2O (0.75 mL) in AcOH (3 mL) was stirred at room temperature for 1 h under nitrogen atmosphere. TLC find new spot (PE / EA 6:1 Rf=0.6). The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (6:1) to afford 4-[(lR,2R)-2-cyanocyclopropyl]benzenesulfonyl chloride (200 mg, 73.20% yield) as a colorless oil.

[1360] d) N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonamide

[1361] The title compound was obtained in analogy to example 156 as a white solid (59.4% yield) using 3-amino-8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 557.00. 1H NMR (400 MHz, Acetonitrile-d3) δ 8.70 (s, 1H), 7.78 (dd, J = 8.4, 2.9 Hz, 1H), 7.73 - 7.68 (m, 2H), 7.47 (ddd, J = 10.3, 7.8, 4.2 Hz, 3H), 7.30 - 7.24 (m, 2H), 7.13 - 7.06 (m, 2H), 5.85 (s, 1H), 3.42 (s, 3H), 2.76 - 2.69 (m, 1H), 1.83 (dddd, J = 9.1, 5.8, 4.8, 3.4 Hz, 1H), 1.69 (dt, J = 9.3, 5.7 Hz, 1H), 1.51 (dddd, J = 9.2, 6.6, 5.5, 2.6 Hz, 1H).

[1362] Example 215: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-hydroxycyclopropyl)benzenesulfonamide

[1363]

[1364] The title compound was obtained in analogy to example 156 as a white solid (9.6% yield) using 3-amino-8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l-hydroxycyclopropyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 548.0. 1H NMR (400 MHz, CD3CN) δ 7.69 (dd, J = 8.4, 2.9 Hz, 1H), 7.64 - 7.56 (m, 2H), 7.44 - 7.33 (m, 3H), 7.31 - 7.25 (m, 2H), 7.06 - 6.96 (m, 2H), 5.73 (s, 1H), 4.46 - 3.84 (m, 1H), 3.33 (s, 3H), 1.21 (dd, J = 4.0, 2.8 Hz, 2H), 1.03 - 0.95 (m, 2H).

[1365] Example 216: N-[8-chloro-6-fluoro-4-oxo-2-[(S)-(4-fhiorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-methoxycyclopropyl)benzenesulfonamide

[1366]

[1367] The title compound was obtained in analogy to example 156 as a white solid (30.7% yield) using 3-amino-8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l-methoxycyclopropyl)benzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 562.15. 1H NMR (400 MHz, DMSO-d6) 5 11.70 (d, J = 168.1 Hz, 1H), 8.13 (s, 1H), 7.84 - 7.69 (m, 2H), 7.57 (d, J = 8.0, 2.9 Hz, 1H), 7.41 (d, J = 8.3 Hz, 4H), 7.21 (s, 2H), 5.81 (s, 1H), 3.33 (s, 3H), 3.20 (s, 3H), 1.30 (d, J = 2.3 Hz, 2H), 1.08 (d, J = 7.2 Hz, 2H).

[1368] Example 217: N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-methoxycyclopropyl)benzenesulfonamide

[1369]

[1370] The title compound was obtained in analogy to example 23 as a white solid (51.4% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-[4-(l-methoxycyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. Chiral separation using conditions J afforded N-[6,8-difhioro-4-oxo-2-[(R)-(4-fhiorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-methoxycyclopropyl)benzenesulfonamide (32.4% yield, RT=3.61min, first peak) as a white solid. LCMS (ESI) [M+H]+: 546.15. 1H NMR (400 MHz, DMSO-d6) 5 11.68 (d, J = 149.2 Hz, 1H), 7.92 (s, 1H), 7.74 (d, J = 8.3 Hz, 2H), 7.42 (dd, J = 12.6, 7.4 Hz, 5H), 7.21 (d, J = 8.5 Hz, 2H), 5.79 (s, 1H), 3.33 (s, 3H), 3.20 (s, 3H), 1.30 (d, J = 2.5 Hz, 2H), 1.08 (d, J = 8.2 Hz, 2H).

[1371] Example 218: N-[8-chloro-6-fluoro-4-oxo-2-[(S)-(4-fhiorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-hydroxycyclopropyl)benzenesulfonamide

[1372]

[1373] The title compound was obtained in analogy to example 156 as a white solid (3.1% yield) using 3-amino-8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l-hydroxycyclopropyl)benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 548.0. 1H NMR (400 MHz, CD3CN) δ 7.69 (dd, J = 8.4, 2.9 Hz, 1H), 7.64 - 7.56 (m, 2H), 7.44 - 7.33 (m, 3H), 7.31 - 7.25 (m, 2H), 7.06 - 6.96 (m, 2H), 5.73 (s, 1H), 4.46 - 3.84 (m, 1H), 3.33 (s, 3H), 1.21 (dd, J = 4.0, 2.8 Hz, 2H), 1.03 - 0.95 (m, 2H).

[1374] Example 219: N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-methoxycyclopropyl)benzenesulfonamide F

[1375] A

[1376] ci

[1377] _ N. X

[1378] T il

[1379] HN^Y^ T

[1380] o=s=o o

[1381]

[1382] The title compound was obtained in analogy to example 156 as a white solid (36.4% yield) using 3-amino-8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-(l-methoxycyclopropyl)benzenesulfonyl chloride. LC-MS (ESI, m / z): [M+ H]+: 562.15. 1H NMR (400 MHz, DMSO-d6) 5 11.70 (d, J = 171.1 Hz, 1H), 8.13 (s, 1H), 7.88 - 7.66 (m, 2H), 7.57 (d, J = 6.5 Hz, 1H), 7.41 (d, J = 8.2 Hz, 4H), 7.21 (s, 2H), 5.80 (s, 1H), 3.34 (d, J = 1.3 Hz, 3H), 3.20 (d, J = 1.3 Hz, 3H), 1.30 (s, 2H), 1.09 (d, J = 9.4 Hz, 2H).

[1383] Example 220: N-[6,8-difluoro-4-oxo-2-[(S)-(4-fhiorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-methoxycyclopropyl)benzenesulfonamide

[1384]

[1385] The title compound was obtained in analogy to example 23 as a white solid (51.4% yield) using 3,5-difluoro-2-[2-(4-fluorophenyl)-2-methoxyacetamido]benzoic acid and N'-[4-(l-methoxycyclopropyl)benzenesulfonyl]tert-butoxycarbohydrazide. Chiral separation using conditions J afforded N-[6,8-difhioro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l-methoxycyclopropyl)benzenesulfonamide (30.6% yield, RT=5.91min, second peak) as a white solid. LCMS (ESI) [M+H]+: 546.15. 1H NMR (400 MHz, DMSO-d6) 5 11.68 (d, J = 149.2 Hz, 1H), 7.92 (s, 1H), 7.74 (d, J = 8.3 Hz, 2H), 7.42 (dd, J = 12.6, 7.4 Hz, 5H), 7.21 (d, J = 8.5 Hz, 2H), 5.79 (s, 1H), 3.33 (s, 3H), 3.20 (s, 3H), 1.30 (d, J = 2.5 Hz, 2H), 1.08 (d, J = 8.2 Hz, 2H).

[1386] Example 221: N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonamide

[1387]

[1388] The title compound was obtained in analogy to example 156 as a white solid (59.5% yield) using 3-amino-8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)(methoxy)methyl]quinazolin-4-one and 4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonyl chloride. LCMS (ESI) [M + H]+: 557.05. 1H NMR (400 MHz, Acetonitrile-d3) δ 8.70 (s, 1H), 7.81 (dd, J = 8.5, 2.9 Hz, 1H), 7.77 - 7.71 (m, 2H), 7.54 - 7.45 (m, 3H), 7.34 - 7.28 (m, 2H), 7.17 - 7.09 (m, 2H), 5.88 (s, 1H), 3.46 (s, 3H), 2.77 (ddd, J = 9.3, 6.7, 4.7 Hz, 1H), 1.91 - 1.84 (m, 1H), 1.73 (dt, J = 9.3, 5.7 Hz, 1H), 1.54 (dddd, J = 9.1, 6.6, 5.5, 2.7 Hz, 1H).

[1389] Example 222: 4-(l-fluoro-l-methyl-ethyl)-N-[5-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[1390]

[1391] The title compound was obtained in analogy to example 6 as a white solid (34.8% yield) using 3-amino-2-[methoxy(phenyl)methyl]-5-methylquinazolin-4-one and 4-(2- fluoropropan-2-yl) benzenesulfonyl chloride. Chiral separation using conditions B afforded 4-(l-fhioro-l-methyl-ethyl)-N-[5-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide (34.9% yield, RT=21.3min, second peak) as a white solid. LCMS(ESI) [M + H]+: 496.25.1H NMR (400 MHz, CD3CN) δ 7.82 – 7.74 (m, 2H), 7.66 (t, J= 7.8 Hz, 1H), 7.57 - 7.44 (m, 5H), 7.43 - 7.31 (m, 3H), 7.24 (dt, 7 = 7.5, 1.1 Hz, 1H), 6.00 (s, 1H), 3.50 (s, 3H), 2.33 (s, 3H), 1.71 (s, 3H), 1.65 (s, 3H).

[1392] Example 223: 4-(l-fluoro-l-methyl-ethyl)-N-[5-methyl-4-oxo-2-[(S)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[1393]

[1394] The title compound was obtained in analogy to example 6 as a white solid (34.8% yield) using 3-amino-2-[methoxy(phenyl)methyl]-5-methylquinazolin-4-one and 4-(2-fluoropropan-2-yl) benzenesulfonyl chloride. Chiral separation using conditions B afforded 4-(l-fhioro-l-methyl-ethyl)-N-[5-methyl-4-oxo-2-[(S)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide (36.7% yield, RT=13.9min, first peak) as a white solid. LCMS(ESI) [M + H]+: 496.25.1H NMR (400 MHz, CD3CN) δ 7.81 – 7.74 (m, 2H), 7.67 (t, J= 7.8 Hz, 1H), 7.57 - 7.44 (m, 5H), 7.43 - 7.31 (m, 3H), 7.24 (dt, 7 = 7.4, 1.1 Hz, 1H), 6.00 (s, 1H), 3.50 (s, 3H), 2.34 (s, 3H), 1.71 (s, 3H), 1.65 (s, 3H).

[1395] Example 224: N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[( 1 S *,2R*) -2-hydroxy cyclobutyl] benzenesulfonamide

[1396]

[1397] a) 4- { 2- [(tert-butyldiphenylsilyl)oxy] cyclobutyl } -N- { 6-fluoro-2- [ (R) -methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}benzenesulfonamide

[1398] The title compound was obtained in analogy to example 87 as a colorless oil (96.0% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4-{2-[(tert-butyldiphenylsilyl)oxy]cyclobutyl}benzenesulfonyl chloride. LCMS (ESI) [M+H]+:

[1399] 748.26.

[1400] b) N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(lS*,2R*)-2-hydroxycyclobutyl] benzene sulfonamide

[1401] To a stirred solution of 4-{2-[(tert-butyldiphenylsilyl)oxy]cyclobutyl]-N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]benzenesulfonamide (400 mg, 0.535 mmol, 1 equiv) in DCM (10 mL) was added TBAF (279.6 mg, 1.070 mmol, 2 equiv) at 0 °C. The resulting mixture was stirred for additional 1 h at 40 °C. The resulting mixture was concentrated under vacuum. The residue was purified by reversed-phase flash chromatography with the following conditions: Column: Xselect CSH Prep Cl 8,

[1402] 30* 150mm 5pm; Mobile Phase A: Water (0.05% TFA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient (B%): isocratic 40% to 56% B in 12 min; Wave Eength: 254 / 220 nm; RT=10.70 min. This resulted in N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(lS*,2R*)-2-hydroxycyclobutyl]benzenesulfonamide (200 mg, 73.39% yield as a white solid. Chiral separation using conditions E afforded N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(lS*,2R*)-2-hydroxycyclobutyl]benzenesulfonamide (20.9% yield, RT=6.22min, first peak) as a white solid. LCMS (ESI) [M+H]+: 510.14. 1H NMR (400 MHz, DMSO-d6) 5 11.41 (s, 1H), 8.00 - 7.55 (m, 5H), 7.43 (d, J = 8.1 Hz, 2H), 7.40 - 7.28 (m, 5H), 5.78 (s, 1H), 5.48 (d, J = 7.2 Hz, 1H), 4.02 - 3.90 (m, 1H), 3.32 (s, 3H), 3.27 (d, J = 18.0 Hz, 1H), 2.20 - 2.09 (m, 1H), 2.08 - 1.96 (m, 1H), 1.85 - 1.71 (m, 1H), 1.58 - 1.44 (m, 1H).

[1403] Example 225: N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(2-hydroxycyclobutyl)methoxy]benzenesulfonamide

[1404]

[1405] a) 4- { [2-(benzyloxy)cyclobutyl]methoxy } -N- { 6-fluoro-2- [(R)-methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl}benzenesulfonamide

[1406] The title compound was obtained in analogy to example 87 as a yellow solid (83.9% yield) using 3-amino-6-fluoro-2-[(R)-methoxy(phenyl)methyl]quinazolin-4-one and 4- { [2-(benzyloxy)cyclobutyl]methoxy}benzenesulfonyl chloride. LCMS (ESI) [M+H]+: 630.0. b) N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(2-hydroxycyclobutyl)methoxy]benzenesulfonamide

[1407] A solution of 4-{[2-(benzyloxy)cyclobutyl]methoxy}-N-{6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl}benzenesulfonamide (150 mg, 0.238 mmol, 1 equiv) and Titanium (IV) chloride (1.0 M in dichloromethane, 1.19 mL, 1.190 mmol, 5 equiv) in DCM (5 mL) was stirred at room temperature for 2 h under nitrogen atmosphere. The reaction was quenched by the addition of sat. NaHCO3 (aq.) (2 mL) at room temperature. The resulting mixture was extracted with EtOAc (3 x 10 mL). The combined organic layers were dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude product was purified by Prep-HPLC with the following conditions (Column: Xbridge Phenyl OBD Column, 30* 150mm 5 pm; Mobile Phase A: Water (0.1%EA), Mobile Phase B: ACN; Flow rate: 60 mL / min; Gradient (B%): 31% B to 48% B in 30 min; Wave Length: 254 / 220 nm; RT=10.23 min) to afford N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(2-hydroxycyclobutyl)methoxy]benzenesulfonamide (64.7 mg, 50.34% yield) as a white solid. LCMS (ESI) [M + H]+: 540.10. 1H NMR (400 MHz, Acetonitrile-d3) 58.47 (s, 1H), 7.70 (s, 1H), 7.65 - 7.57 (m, 2H), 7.57 - 7.46 (m, 1H), 7.46 - 7.39 (m, 1H), 7.39 -7.12 (m, 5), 6.93 - 6.85 (m, 2H), 5.80 (s, 1H), 4.03 - 3.84 (m, 3H), 3.35 (s, 3H), 3.13 (s, 1H), 2.48 - 2.33 (m, 1H), 2.09 (d, J = 7.3 Hz, 1H), 1.77 - 1.57 (m, 2H), 1.33 - 1.14 (m, 1H). Example 226: N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[( 1R*,2S *) -2-hydroxy cyclobutyl] benzenesulfonamide

[1408]

[1409] The title compound is the second peak obtained in the chiral separation of N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(lS*,2R*)-2-hydroxycyclobutyl]benzenesulfonamide (Example 224) using conditions E (22.4% yield, RT=7.8min, second peak) as a white solid. LCMS (ESI) [M+H]+: 510.14. 1H NMR (400 MHz, DMSO-d6) 5 11.41 (s, 1H), 7.89 (s, 1H), 7.72 (d, J = 8.3 Hz, 3H), 7.60 (d, J = 8.2 Hz, 1H), 7.51 - 7.29 (m, 7H), 5.80 (s, 1H), 5.48 (d, J = 7.2 Hz, 1H), 4.03 - 3.91 (m, 1H), 3.34 - 3.32 (m, 4H), 2.20 - 2.09 (m, 1H), 2.08 - 1.96 (m, 1H), 1.85 - 1.71 (m, 1H), 1.57 -1.43 (m, 1H).

[1410] Example 227: 4-[[(ls,3s)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide

[1411]

[1412] 4-[[(ls,3s)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide was obtained in analogy to Example 199 as a white solid (26.6% yield) using N-{6,8-difluoro-2-[(4-fluorophenyl)(methoxy)methyl]-4-oxoquinazolin-3-yl}-4- iodobenzene sulfonamide and (ls,3s)-3-(difluoromethyl)cyclobutan-l-amine. Chiral separation using conditions F afforded 4-[[(ls,3s)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide (36.8% yield, RT=6.81min, first peak) as a white solid. LCMS (ESI) [M + H]+: 595.10. 1H NMR (400 MHz, Acetonitrile-d3) 58.45 (s, 1H), 7.54 - 7.36 (m, 6H), 7.11 (t, J = 8.8 Hz, 2H), 6.58 -6.50 (m, 2H), 6.05 - 5.74 (m, 2H), 5.61 (d, J = 6.7 Hz, 1H), 3.95 (p, J = 7.5 Hz, 1H), 3.44 (s, 3H), 2.64 - 2.45 (m, 3H), 1.90 (t, J = 11.7 Hz, 2H).

[1413] Example 228: 4-methyl-N-[8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide

[1414]

[1415] The title compound was obtained in analogy to Example 87 as a white solid (73.8% yield) using 3-amino-2-[(R)-methoxy(phenyl)met...

Claims

Claims1. A compound of formula (I)whereinR1is hydrogen, alkyl or halogen;R2is hydrogen or halogen;R3is hydrogen or halogen;R4is hydrogen, alkyl, halogen, alkoxy, alkoxyalkyl, hydroxyalkyl, haloalkyl, haloalkoxy, cycloalkyl, cycloalkoxy, halocycloalkylalkylamino or azetidinyl;R5is hydrogen, halogen, hydroxyl or alkoxy;R6is hydrogen or halogen;R7is hydrogen, halogen or alkyl;R8is hydrogen, halogen or alkoxy; andR9is substituted phenyl, 2,3-dihydro-l,4-benzodioxyl, halothiophenyl, indolinone, alkylindolyl, alkylthiophenyl, dialkylthiophenyl, haloalkylthiophenyl, hydroxyalkylthiophenyl, haloalkenylthiophenyl, halocycloalkylthiophenyl, hydroxycycloalkylthiophenyl, alkylthiazolyl or alkylpyridinyl wherein substituted phenyl is phenyl substituted with one or two substituents selected from halogen, alkyl, alkoxy, haloalkoxyalkyl, alkyloxoamino and alkyloxoaminoalkyl or with one substituent selected from cycloalkyl, halocycloalkyl, halocycloalkylalkyl, halocycloalkylamino, haloalkylcycloalkylamino, halocycloalkoxy, haloalkyl, haloalkoxyalkyl, hydroxyalkyl, haloalkoxy, hydroxycycloalkyl, hydroxycycloalkylalkoxy, alkoxyalkyl, alkoxycycloalkyl, alkoxyhaloalkyl, alkinyl, dialkylamino,(halo)(cycloalkyl)alkyl, (halo)(cycloalkyl)alkoxy, cyanocycloalkyl, alkenyl, haloazetidinyl, haloalkylazetidinyl, alkoxyazetidinyl, alkoxyalkylazetidinyl, halopiperidinyl, quinolinyl, morpholinyl, alkoxypyrrolidinyl, tetrahydrofuranyl, (tetrahydrofuranyl) (alkyl) amino, oxazolylmethyl pyrrolyl, haloalkoxycycloalkylamino, haloalkylcycloalkyloxy and haloalkylamino; or a pharmaceutically acceptable salt thereof;provided thatN-[4-[[[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl] amino] sulfonyl]phenyl] -acetamide;N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(trifluoromethoxy)-benzenesulfonamide;3.4-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(trifluoromethyl)-benzenesulfonamide;4-chloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-(l-methylethyl)-benzenesulfonamide;N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-4-methoxy-benzenesulfonamide;3,4-difluoro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;2-chloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-3,4-dimethoxy-benzenesulfonamide;3,5-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide;4-fluoro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;4-(1,1-dimethylethyl)-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]-benzenesulfonamide; and2,4-dichloro-N-[6-fluoro-4-oxo-2-(phenylmethyl)-3(4H)-quinazolinyl]- benzenesulfonamide;are excluded.

2. A compound according to claim 1, wherein R1is hydrogen, methyl or chlorine.

3. A compound according to claim 1 or 2, wherein R2is hydrogen or fluorine.

4. A compound according to any one of claims 1 to 3, wherein R3is hydrogen.

5. A compound according to any one of claims 1 to 4, wherein R4is hydrogen, alkyl, halogen, alkoxy, haloalkyl, haloalkoxy or cycloalkoxy.

6. A compound according to any one of claims 1 to 5, wherein R4is hydrogen, methyl, fluorine, chlorine, methoxy, fluoromethyl, difluoroethyl, difluoroethoxy or cylcopropyloxy.

7. A compound according to any one of claims 1 to 6, wherein R5is hydrogen or alkoxy.

8. A compound according to any one of claims 1 to 7, wherein R5is hydrogen or methoxy.

9. A compound according to any one of claims 1 to 8, wherein R5is methoxy.

10. A compound according to any one of claims 1 to 9, wherein R6is hydrogen.

11. A compound according to any one of claims 1 to 10, wherein R7is hydrogen.

12. A compound according to any one of claims 1 to 11, wherein R8is hydrogen or halogen.

13. A compound according to any one of claims 1 to 12, wherein R8is hydrogen or fluorine.

14. A compound according to any one of claims 1 to 13, wherein R9is substituted phenyl, 2,3-dihydro-l,4-benzodioxyl, alkylthiophenyl, dialkylthiophenyl,haloalkylthiophenyl halocycloalkylthiophenyl or hydroxyalkylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent selected from alkyl, haloalkyl, halocycloalkyl, hydroxycycloalkyl, alkoxycycloalkyl, halocycloalkoxy, morpholinyl, haloalkoxyalkyl, cyanocycloalkyl, halocycloalkylamino, haloalkylcycloalkylamino, haloalkoxycycloalkylamino, haloalkylcycloalkyloxy and haloalkylamino.

15. A compound according to any one of claims 1 to 14, wherein R9is substituted phenyl, 2,3-dihydro-1,4-benzodioxyl, methylthiophenyl, dimethylthiophenyl, fluoromethylthiophenyl, difluoromethylthiophenyl, fluorocyclopropylthiophenyl or hydroxymethylthiophenyl, wherein substituted phenyl is phenyl substituted with one substituent selected from methyl, difluoroethyl, fluorocyclopropyl, hydroxycyclopropyl, methoxycyclopropyl, difluorocyclopropyl, morpholinyl, difluoromethoxymethyl, cyanocyclopropyl, difluorocyclopropyloxy, fluorocyclobutylamino, difluorocyclobutylamino, difluoromethylcyclobutylamino, difluoroethyloxycyclobutylamino, difluoromethylcyclobutyloxy and trifluoroethylamino.

16. A compound according to any one of claims 1 to 15 selected fromN-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,3-dihydro-l,4-benzodioxine-6- sulfonamide;N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide;N-[6-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl- benzenesulfonamide;N-[7-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl- benzenesulfonamide;N-[2-[(4-chlorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-4-methoxy-2- (trifluoromethyl)benzenesulfonamide;4-fhioro-N-[6-fhioro-2-[(4-fhiorophenyl)methyl]-4-oxo-quinazolin-3- yl] benzenesulfonamide;N-(2-benzyl-8-methyl-4-oxo-quinazolin-3-yl)-5-chloro-thiophene-2-sulfonamide;N-[6,7-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl- benzenesulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;2-chloro-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-y 1] benzenesulfonamide;N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-4-cyclopropyl-benzenesulfonamide; 5-chloro-N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]thiophene-2- sulfonamide;N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-3-fluoro-4-methyl-benzenesulfonamide;N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide;N-[2-[(3,4-difluorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-4-fluoro-benzenesulfonamide;4-fluoro-N-[6-fluoro-2-[(3-fluoro-4-methyl-phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide;N-[6-chloro-2- [methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] -4-( 1 -fluoro- 1 -methyl-ethyl)benzenesulfonamide;N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide;4-( 1 -fluoro- 1 -methyl-ethyl)-N- [2- [methoxy(phenyl)methyl] -5-methyl-4-oxo-quinazolin- 3 -yl] benzenesulfonamide;5-bromo-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2- sulfonamide;5-chloro-N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2- sulfonamide;N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide;5-chloro-N-[8-chloro-6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-y 1] thiophene-2- sulfonamide;N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-5-chloro-thiophene-2-sulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-2-oxo-indoline-5-sulfonamide;N-[6-fluoro-2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide;N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide;N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide;N-(2-benzyl-5-chloro-4-oxo-quinazolin-3-yl)-2-chloro-4-fluoro-benzenesulfonamide;N-(2-benzyl-5-chloro-8-fluoro-4-oxo-quinazolin-3-yl)-4-chloro-benzenesulfonamide;4-chloro-N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;N-(2-benzyl-5-chloro-8-fluoro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide;N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-(difluoromethyl)benzene sulfonamide;N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide;N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-(difluoromethyl)benzene sulfonamide;N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-4-ethynyl-benzenesulfonamide;N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-ethyl-benzenesulfonamide;N-[8-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-5-(difluoromethyl)thiophene-2-sulfonamide;N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(trifluoromethyl)benzenesulfonamide;N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;4-( 1, 1 -difluoroethyl)-N- [6-fluoro-2- [methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin- 3 -yl] benzenesulfonamide;5-chloro-N-[8-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2- sulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-2-[fluoro(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-(2-benzyl-8-methyl-4-oxo-quinazolin-3-yl)-3-fluoro-benzenesulfonamide;N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;4-(difluoromethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin- 3 -yl] benzenesulfonamide;N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(difluoromethyl)benzene sulfonamide;4-methoxy-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide;4-(dimethylamino)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-2-[(3-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[5-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methoxy-benzenesulfonamide;3-fluoro-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]- 4-methyl-benzenesulfonamide;N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;N-(6-fluoro-2-(methoxy(phenyl)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methoxybenzenesulfonamide;N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(1-fluorocyclopropyl)benzenesulfonamide;N-(6-fluoro-2-((2-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;N-(2-benzyl-8-methoxy-4-oxo-quinazolin-3-yl)-4-methyl-benzenesulfonamide; N-[2-[fluoro(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-5-methyl-thiophene-2- sulfonamide;N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4- (dimethylamino)benzenesulfonamide;N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide;4-(dimethylamino)-N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-y 1] benzenesulfonamide;N-[6-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino )benzenesulfonamide;4-(difluoromethyl)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin- 3 -yl] benzenesulfonamide;N-[5-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(dimethylamino)benzenesulfonamide;4-(dimethylamino)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin- 3 -yl] benzenesulfonamide;N-[2-[(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;4-(1,1-difluoroethyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[6-fluoro-2-[methoxy-(4-methoxyphenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;N-[8-(hydroxymethyl)-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[8-(fluoromethyl)-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]quinoline-6-sulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-isopropenyl-benzenesulfonamide;4-( 1 -fluorocyclopropyl)-N- [8-methoxy-2- [methoxy(phenyl)methyl] -4-oxo-quinazolin- 3 -yl] benzenesulfonamide;N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;(R)-4-(3 -difluoroazetidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;(R)-4-(4,4-difluoropiperidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;(R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-morpholinobenzene sulfonamide;4-(2,2-difluorocyclopropyl)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;(R)-4-(2,2-difluoroethoxy)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;(R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((l-fluorocyclopropyl)methoxy)benzenesulfonamide;N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(l-fluoro-2-methylpropyl)benzenesulfonamide;(R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-4-(3-(difluoromethyl)azetidin-l-yl)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;(R)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(3-methoxyazetidin- 1 -yl)benzenesulfonamide;4-(2,2-difluoroethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3 -yl] benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(3-methoxypyrrolidin- 1 -yl)benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-[methyl(tetrahydrofuran-3-yl)amino]benzenesulfonamide;4-(2,2-difluorocyclobutyl)-N - [6-fluoro-4-oxo-2- [(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-[3-(methoxymethyl)azetidin- 1 -yl] benzene sulfonamide;N-[8-cyclopropyl-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin- 3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(oxetan-2-yl)benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide;N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-fluoro-benzenesulfonamide;N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-2-(trifluoromethyl)benzenesulfonamide;N-[2-[(4-chlorophenyl)methyl]-6-fluoro-4-oxo-quinazolin-3-yl]-2- (trifluoromethyl)benzenesulfonamide;N-[6-chloro-2-(m-tolylmethyl)-4-oxo-quinazolin-3-yl]-2- (trifluoromethyl)benzenesulfonamide;N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2- (trifluoromethyl)benzenesulfonamide;N-[7-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-isopropyl-benzenesulfonamide;4-isopropyl-N-[2-[methoxy(phenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl] benzenesulfonamide;N-(2-benzyl-6-chloro-4-oxo-quinazolin-3-yl)-2- (trifluoromethyl)benzenesulfonamide;N-[2-[(4-chlorophenyl)methyl]-5-methyl-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide;N-[5-methyl-2-(m-tolylmethyl)-4-oxo-quinazolin-3-yl]-2-(trifluoromethyl)benzenesulfonamide;N-[4-[(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)sulfamoyl]-3-(trifluoromethyl)phenyl] acetamide;N-(2-benzyl-6-fluoro-4-oxo-quinazolin-3-yl)-4-fluoro-2-methyl-benzenesulfonamide;N-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,6-dichloro-benzenesulfonamide;N-(2-benzyl-6-fluoro-5-methyl-4-oxo-quinazolin-3-yl)-2-chloro-4-fluoro-benzenesulfonamide;N-(2-benzyl-8-chloro-4-oxo-quinazolin-3-yl)-4-chloro-benzenesulfonamide;N-(2-benzyl-8-chloro-5-fluoro-4-oxo-quinazolin-3-yl)-2-chloro-benzenesulfonamide;4-chloro-N-[5-chloro-2-[hydroxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;2-chloro-N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;4-(l,l-difluoroethyl)-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl] benzenesulfonamide;5-bromo-N-[6-fluoro-2-[fluoro(phenyl)methyl]-4-oxo-quinazolin-3-yl]thiophene-2-sulfonamide;N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylpyridine-2- sulfonamide;4-(difluoromethoxy)-N-(6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;N-[5-chloro-2-[hydroxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;3-cyclopropyl-N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-y 1] benzenesulfonamide;4-(dimethylamino)-N-(7-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;4-(dimethylamino)-N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-methyl-4-oxo-quinazolin- 3 -yl] benzenesulfonamide;N-[6-chloro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(l,l-difluoroethyl)benzenesulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-(l-hydroxy- 1 -methyl-ethyl)benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(2-methoxypropyl)benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethoxy)benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;4-( 1 -cyanocyclopropyl)-N- [6-fluoro-4-oxo-2- [(R) -methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;4-(difluoromethoxymethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(oxazol-2-ylmethyl)benzenesulfonamide;N-[8-(fluoromethyl)-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-methyl-4-oxo-quinazolin-3-yl]- 1 -methyl-indole-6- sulfonamide;N-[8-(fluoromethyl)-4-oxo-2-[(S)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;N- [ [4- [ [6-fluoro-4-oxo-2- [(R)-methoxy(phenyl)methyl] quinazolin-3-y 1] sulfamoyl]phenyl]methyl] acetamide;N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;4-(2,2-difluoro-3-methoxy-propyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;4-(2,2-difluorocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;N-[8-[(3 -difluorocyclobutyl)methylamino]-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[8-(azetidin-l-yl)-6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;4-[(2,2-difluorocyclopropyl)methyl]-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxo-8-(2,2,2-trifluoroethyl)quinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;(R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(8-(2,2-difluoroethoxy)-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3 (4H) -yl) -4- ( 1 -fluorocyclopropyl)benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(l-fluorocyclobutyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l -cyanocycloprop yl)benzenesulfonamide;N-[8-chloro-6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(2,2-difluorocyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl] -4-( 1 -fluorocyclopropyl)benzenesulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-8-(isopropoxymethyl)-4-oxo-quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-( 1 -fluorocyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(lH-pyrrol-2-yl)benzenesulfonamide;(R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-(2,2-difluoroethyl)thiophene-2- sulfonamide;(R)-N-(8-cyclopropoxy-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(l-fluorocyclopropyl)benzenesulfonamide;(R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl) - 5 -methylthiophene-2- sulfonamide;(R)-N-(8-methoxy-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;(R)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin- 3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;4-(2,2-difluorocyclopropoxy)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;(S)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;(S)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;5 -(fluoromethyl) -N- (2-((4-fluorophenyl) (methoxy )methyl) - 8 -methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-3-methyl-1H-indole-6-sulfonamide;N-(8-(2,2-difluoroethoxy)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;(R)-4-(1-fluorocyclopropyl)-N-(8-(fluoromethyl)-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;N-(6,8-difluoro-2-((S)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((1s,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide;N-(6,8-difluoro-2-((R)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((1s,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide;(R)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;(S)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)-5-(hydroxymethyl)thiophene-2-sulfonamide;N-[8-(difluoromethyl)-2-[(S)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide;N-[8-(difluoromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide;N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide;4-( 1, 1 -difluoroethyl)-N- [8-(fluoromethyl)-2- [(R)-methoxy(phenyl)methyl] -4-oxoquinazolin-3-yl]benzenesulfonamide;N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide;(R)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H) -yl) -5 - (fluoromethyl) thiophene-2- sulfonamide;(S)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H) -yl) -5 - (fluoromethyl) thiophene-2- sulfonamide;(S)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-3,5-dimethyl-thiophene-2-sulfonamide;N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-2-methyl- thiazole- 5 - sulfonamide;5-(1-fluorocyclopropyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]thiophene-2-sulfonamide;4-(1-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl] -5 - (difluoromethyl)thiophene-2- sulfonamide;5-(l-chlorocyclopropyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]thiophene-2-sulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-[(E)-3-fluoroprop-l-enyl]thiophene-2-sulfonamide;4-[(3 -difluorocyclobutyl)amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;N-[8-chloro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;4-(1-cyanocyclopropyl)-N-[8-(2,2-difluoroethoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-(l-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-(l-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] benzenesulfonamide;4-(l-cyanocyclopropyl)-N-[8-(cyclopropoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-(1-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-(l-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;5-(hydroxymethyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide;5-(hydroxymethyl)-N-[6-fluoro-8-methyl -4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide;(R)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;5-(1-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(l-fluorocyclopropyl)thiophene-2-sulfonamide;5-(l-hydroxycyclopropyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5-(hydroxymethyl)thiophene-2-sulfonamide;N-[8-chloro-6-fluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(lRS,2RS)-2-cyanocyclopropyl]benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl] -4-( 1 -hydroxycyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-( 1 -methoxycyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl] -4-( 1 -hydroxycyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-( 1 -methoxycyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-[(1RS,2RS)-2-cyanocyclopropyl]benzenesulfonamide;4-( 1 -fluoro- 1 -methyl-ethyl)-N- [5-methyl-4-oxo-2- [(R) -methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;4-( 1 -fluoro- 1 -methyl-ethyl)-N- [5-methyl-4-oxo-2- [(S)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(1S*,2R*)-2-hydroxycyclobutyl] benzene sulfonamide;N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(2-hydroxycyclobutyl)methoxy]benzenesulfonamide;N-[6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-[(lR*,2S*)-2-hydroxycyclobutyl] benzene sulfonamide;4-[[(ls,3s)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-methyl-N-[8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl] benzenesulfonamide;(R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)-3-methylbenzenesulfonamide;(S)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)-3-methylbenzenesulfonamide;4-[[(ls,3s)-3-(2,2-difluoroethoxy)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-[[(lr,3r)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-[(lr,3r)-3-(difluoromethyl)cyclobutoxy]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethylamino)benzenesulfonamide;N-[6-fluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin- 3-yl]-4-[[(lr,3r)-3 - (trifluoromethyl)cyclobutyl] amino] benzene sulfonamide;4-[[(lr,3r)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-[[(ls,3s)-3-(2,2-difluoroethoxy)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(S)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(2,2,2-trifluoroethylamino)benzenesulfonamide;N-[6,8-difluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4- [[(lr,3r)-3-(trifluoromethyl)cyclobutyl]amino]benzenesulfonamide;N-[6,8-difluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4- [[(lr,3r)-3-(trifluoromethyl)cyclobutyl]amino]benzenesulfonamide; andN-[6-fluoro-2-[(S)-(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin- 3-yl]-4-[[(lr,3r)-3 - (trifluoromethyl) cyclobutyl] amino] benzene sulfonamide;or a pharmaceutically acceptable salt thereof.

17. A compound according to any one of claims 1 to 16 selected fromN-(2-benzyl-5-methyl-4-oxo-quinazolin-3-yl)-2,3-dihydro-l,4-benzodioxine-6- sulfonamide;N-[2-[methoxy(phenyl)methyl]-8-methyl-4-oxo-quinazolin-3-yl]-4-methyl- benzenesulfonamide;N-[6-fluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4-methyl- benzenesulfonamide;N-[6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl- benzenesulfonamide;N-[5-chloro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl- benzenesulfonamide;N-[6,8-difluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-methyl- benzenesulfonamide;N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4- methylbenzenesulfonamide;N-[2-[(4-fluorophenyl)-methoxy-methyl]-8-methoxy-4-oxo-quinazolin-3-yl]-4- methyl-benzenesulfonamide;N-[6,8-difluoro-2-[(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3-yl]-4- methyl-benzenesulfonamide;4-(l,l-difluoroethyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)- methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[8-chloro-6-fluoro-2-[methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;(R)-N-(6,8-difluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;4-(2,2-difluoroethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3 -yl] benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-morpholino-benzenesulfonamide;N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;4-(difluoromethoxymethyl)-N-[6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[8-(fluoromethyl)-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-methyl-benzenesulfonamide;N-[6-fluoro-8-methyl-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-5-methyl-thiophene-2-sulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;4-(2,2-difluorocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-methoxy(phenyl)methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;(R)-N-(8-chloro-6-fluoro-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;(R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(8-(2,2-difluoroethoxy)-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3 (4H) -yl) -4- ( 1 -fluorocyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(l -cyanocycloprop yl)benzenesulfonamide;N-[8-chloro-6-fluoro-2-[(R)-methoxy(phenyl)methyl]-4-oxo-quinazolin-3-yl]-4-(2,2-difluorocyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl] -4-( 1 -fluorocyclopropyl)benzenesulfonamide;(R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl) - 5 -methylthiophene-2- sulfonamide;(R)-N-(8-methoxy-2-(methoxy(phenyl)methyl)-4-oxoquinazolin-3(4H)-yl)-5-methylthiophene-2- sulfonamide;(R)-N-(8-(2,2-difluoroethyl)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin- 3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;4-(2,2-difluorocyclopropoxy)-N-(6-fluoro-2-((R)-methoxy(phenyl)methyl)-4-oxoquinazolin-3 (4H) -yl)benzene sulfonamide;N-(8-(2,2-difluoroethoxy)-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(6,8-difluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-((difluoromethoxy)methyl)benzenesulfonamide;N-(6,8-difluoro-2-((R)-(4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H)-yl)-4-(((1s,3s)-3-fluorocyclobutyl)amino)benzenesulfonamide;(R)-5-(fluoromethyl)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methyl-4-oxoquinazolin-3(4H)-yl)thiophene-2-sulfonamide;N-[8-(difluoromethyl)-2-[(R)-methoxy(phenyl)methyl]-4-oxoquinazolin-3-yl]-4-methylbenzenesulfonamide;N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxymethyl]-4-oxoquinazolin-3-yl]-4-[((ls,3s)-3-fluorocyclobutyl)amino]benzenesulfonamide;(R)-N-(2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)-4-methylbenzenesulfonamide;(R)-N-(8-chloro-6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-4-oxoquinazolin-3(4H) -yl) -5 - (fluoromethyl) thiophene-2- sulfonamide;N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-3,5-dimethyl-thiophene-2-sulfonamide;4-(1-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl] -5 - (difluoromethyl)thiophene-2- sulfonamide;4-[(3,3-difluorocyclobutyl)amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;N-[8-chloro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4-(1-fluorocyclopropyl)benzenesulfonamide;4-(1-cyanocyclopropyl)-N-[8-(2,2-difluoroethoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-(l-cyanocyclopropyl)-N-[8-(cyclopropoxy)-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-(1-cyanocyclopropyl)-N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-(l-cyanocyclopropyl)-N-[6-fluoro-8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;5-(hydroxymethyl)-N-[8-methyl-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]thiophene-2-sulfonamide;(R)-4-((difluoromethoxy)methyl)-N-(6-fluoro-2-((4-fluorophenyl)(methoxy)methyl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)benzenesulfonamide;5-(l-fluorocyclopropyl)-N-[8-methoxy-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy- methyl] quinazolin- 3 -yl] thiophene-2- sulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-5- (l-fluorocyclopropyl)thiophene-2-sulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3- yl] -4-( 1 -hydroxycyclopropyl)benzenesulfonamide;N-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4- ( 1 -methoxycyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3- yl]-4-(1-methoxycyclopropyl)benzenesulfonamide;N-[8-chloro-6-fluoro-2-[(R)-(4-fluorophenyl)-methoxy-methyl]-4-oxo-quinazolin-3- yl]-4-[(1RS,2RS)-2-cyanocyclopropyl]benzenesulfonamide;4-[[(ls,3s)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4- fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-[[(ls,3s)-3-(2,2-difluoroethoxy)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)- (4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-[[(lr,3r)-3-(difluoromethyl)cyclobutyl]amino]-N-[6,8-difluoro-4-oxo-2-[(R)-(4- fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide;4-[(lr,3r)-3-(difluoromethyl)cyclobutoxy]-N-[6,8-difluoro-4-oxo-2-[(R)-(4- fluorophenyl)-methoxy-methyl]quinazolin-3-yl]benzenesulfonamide; andN-[6,8-difluoro-4-oxo-2-[(R)-(4-fluorophenyl)-methoxy-methyl]quinazolin-3-yl]-4- (2,2,2-trifluoroethylamino)benzenesulfonamide;or a pharmaceutically acceptable salt thereof.

18. A process for the preparation of a compound according to any one of claims 1 to 17 comprising one of the following steps:(a) The reaction of a compound of formula (A)(A)in the presence of R9SO2C1 and a base; or(b) The reaction of a compound of formula (B)in the presence of R9SO2NH-NHRp and PCl3;wherein R1to R9are as defined in any one of claims 1 to 15 and wherein Rp is hydrogen or an amine protecting group.

19. A compound according to any one of claims 1 to 17, when manufactured according to a process of claim 18.

20. A compound according to any one of claims 1 to 17 for use as therapeutically active substance.

21. A pharmaceutical composition comprising a compound in accordance with any one of claims 1 to 17 and a therapeutically inert carrier.

22. The use of a compound according to any one of claims 1 to 17 or N-(2-benzyl-6- fluoro-4-oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide for the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders.

23. The use of a compound according to any one of claims 1 to 17 or N-(2-benzyl-6- fluoro-4-oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide for the preparation of a medicament for the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders.

24. A compound according to any one of claims 1 to 17 or N-(2-benzyl-6-fluoro-4- oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide for use in the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders.

25. A method for the treatment or prophylaxis of synucleinopathies, Parkinson’s disease, Dementia with Lewy body disease, REM-sleep behavior disorder, amyotrophic lateral sclerosis or lysosomal storage disorders, which method comprises administering an effective amount of a compound as defined in any one of claims 1 to 17 or N-(2-benzyl-6-fluoro-4-oxoquinazolin-3-yl)-4-fluorobenzenesulfonamide to a patient in need thereof.

26. The invention as hereinbefore described.***

Images