Heterocyclic compounds as Delta-5 Desaturase inhibitors and methods of use

Abstract

The present disclosure provides compounds useful for the inhibition of Delta-5 Desaturase ("D5D"). The compounds have a general Formula (I): wherein the variables of Formula (I) are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a metabolic or cardiovascular disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula (I).

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims benefit of U.S. Provisional Patent Application No. 62 / 939,819, filed November 25, 2019, which is incorporated by reference in its entirety. FIELD The present disclosure provides compounds useful for the inhibition of Delta-5 Desaturase (“D5D”). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treatment of, for example, a metabolic or cardiovascular disorder. Further, the disclosure provides intermediates useful in the synthesis of compounds of Formula I, BACKGROUND Polyunsaturated fatty acids (‘TUFAs”) exert important physiological functions in the human body. Kroeger J and Schulze MB, 2012, page 4. PUFAs serve as sources of energy and structural components of cell membranes. Id. PUFAs also regulate genes and are biosynthetic precursors of other physiologically relevant biomolecules, such as eicosanoids and endocannabinoids. Id. Di Marzo V and Matias I, 2005, page 585. Eicosanoids are signaling molecules that have multiple functions and regulate, among other things, the human inflammatory response. Harizi H et a / ., 2008. Endocannabinoids (N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoyl glycerol (2-AG) are endogenous ligands for the cannabinoid receptors which have been established to have a role in food intake and energy balance. Di Marzo V and Matias I, 2005, page 585, Yashiro H el al., 2016, page 2 / 18. Obukowicz MG etal., 1998, page 158. Di Marzo V and Matias I, 2005, page 585. The pertinent part of the metabolic pathway of a certain PUFA, linoleic acid (“LA”), which leads, among other things, to the formation of anti- and pro-inflammatory eicosanoids and endocannabinoids, is shown in the scheme above. The desaturase enzymes, which catalyze certain steps in the conversion of LA in AA are delta-6-desaturase (“D6D;” encoded by the gene Fatty Acid Desaturase 2 (“FADS2”)) and delta-5-desaturase (“D5D;” encoded by the gene Fatly Acid Desaturase I CFADS1”)). Yashiro H ei al., 2016, page 2 / 18. Selectively inhibiting DSD activity reduces the amount of AA generated, while increasing the amount of DGLA. Such a pharmacological intervention reduces downstream generation of, for example, pro-inflammatory eicosanoids and endocannabinoids and leads to build-up of anti-inflammatory eicosanoids, both of which may overall ameliorate inflammation-related conditions and may improve energy balance. Yashiro H el al., 2016, page 3 / 18. Di Marzo V and Matias I, 2005, page 585. This is especially relevant in subjects with high intake of LA, for example, humans exposed to Western-style diets. Yashiro H et al., 2016, page 3 / 18. The FADS1-3 locus has been associated with many metabolic traits in human genome-wide association studies including fasting glucose, plasma lipids, and body weight. Fumagalli M ei al., 2015. Willer CJ el al., 2013. Dupuis J ei al., 2010. An increase or 2020391161   25 Nov 2025 elevation of each metabolic trait is associated with the FADS1-3 locus is also associated with an increase in the activity of D5D as estimated by AA:DGLA ratios. Fumagalli M et al., 2015. Merino DM et al., 2011. In addition to human genetic evidence supporting a role of FADS1 / D5D in metabolic disorders, FADS1 knock out (“KO”) mice also show a phenotype with protection from diet-induced obesity including low body fat content, improved glycemic control, and decreased circulating lipid levels. Powell DR et al., 2016, page 197. In addition, the FADS1 KO mice are resistant to the development of arterial atheromatous plaque. Id. Desaturase enzyme activity has been linked to a variety of diseases, in particular metabolic and cardiovascular diseases, such as obesity, diabetes, nonalcoholic steatohepatitis (“NASH”), dyslipidemia, and coronary artery disease. Tosi F et al., 2014; Kroeger J and Schulze MB, 2012; and Merino DM et al., 2010. Therefore, the pharmacological inhibition of D5D is a target of interest for treating metabolic, cardiovascular and other diseases. Powell DR et al., 2016, page 197. Despite some progress in the area of small molecule therapeutics (for example, Miyahisa I et al., 2016; Yashiro H et al., 2016; and Baugh SD et al., 2015), a need for inhibitors of D5D, which may be suitable for use as therapeutic agents, remains in view of the significant continuing societal burden caused by, for example, metabolic and cardiovascular diseases (for example, Haidar YM and Cosman BC, 2011; Mendis S et al., 2007; Chopra M et al., 2002; and Monteiro CA et al., 2004). Any reference to publications cited in this specification is not an admission that the disclosures constitute common general knowledge in Australia. SUMMARY In a first aspect there is provided a compound of Formula I 2020391161   25 Nov 2025 or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein wherein Rw is H, F, Cl, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -N(CH3)2, -NH(COCH3), -N(CH3)C(=O)F, methyl, ethyl, -CD3, cyclopropyl, -CH=CH2, -OCD3, or 1,3-oxazol-2-yl; wherein the methyl group is optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2, and -N(CH3)2; Ry is H, F, Cl, -OH, -CN, -CONH2, -NH2, C1-4alkylamino, diC1-4alkylamino, C1-4alkoxy, or C1-4deuteroalkoxyl; wherein the C1-4alkoxy is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, C1-4alkoxy, -NH2, and diC1-4alkylamino; Rx and Rz are independently H, halogen, -OH, -CN, -CONH2, -NH2, C1-4alkylamino, diC1-4alkylamino, C1-4alkoxy, or C1-4deuteroalkoxyl; wherein the C1-4alkoxy is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, C1-4alkoxy, -NH2, and diC1-4alkylamino; Mn-R3 ^SQn-R3 R2 is     N     or n"N R3 is C2-6alkyl or C1-3alkoxy; wherein the C2-6alkyl and C1-3alkoxy groups are optionally substituted with 3-5 halogen atoms; and R4 is C1-3alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4haloalkoxy, C3-5cycloalkyl, or C3-5cyclohaloalkyl. In a second aspect there is provided a compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is (2R)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile; (2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile; (4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-pyrazol-1-yl)acetonitrile; 2020391161   25 Nov 2025 (4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)acetonitrile; (4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenyl)acetonitrile; (4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)acetonitrile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)-2-methylpropanenitrile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile; 2-(difluoromethyl)-3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-4H-pyrido[1,2-a]pyrimidin-4-one; 2-(difluoromethyl)-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile; 2-(difluoromethyl)-8-methoxy-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-(difluoromethyl)-8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-(difluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-(difluoromethyl)-8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-(fluoromethyl)-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile; 2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2,8-dimethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-cyclopropyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-ethoxy-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-ethoxy-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 2-ethyl-8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-ethyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-ethyl-8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione; 3-(1-(2,2-difluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-{[(1R)-2,2-difluorocyclopropyl]methyl}-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-{[(1S)-2,2-difluorocyclopropyl]methyl}-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-benzofuran-2-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-cyclopropyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-cyclopropyl-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-phenyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-propyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(2-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(2-fluoro-4-(trifluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(2-fluoro-6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(3-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(((1R)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(((1S)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione; 3-(4-(2,2,2-trifluoroethoxy)phenyl)-2,8-bis(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoroethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoroethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoropropoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-pyrazol-1-yl)propanenitrile; 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenyl)propanenitrile; 3-(4-(cyclopropylmethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(cyclopropylmethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(cyclopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(difluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(5-(2,2,2-trifluoroethoxy)-2-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(5-fluoro-6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-[5-iodo-1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,3-triazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-{1-[(2,2-difluorocyclopropyl)methyl]-1H-pyrazol-4-yl}-7-fluoro-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-{1-[(2,2-difluorocyclopropyl)methyl]-1H-pyrazol-4-yl}-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-{1-[(3,3-difluorocyclobutyl)methyl]-1H-pyrazol-4-yl}-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile; 4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylic acid; 2020391161   25 Nov 2025 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylic acid; 4-oxo-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-7-carbonitrile; 7-(methoxymethyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-8-methoxy-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-8-methyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-8-methyl-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-cyclopropyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 7-cyclopropyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-fluoro-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 7-fluoro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-fluoro-8-hydroxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 7-fluoro-8-methoxy-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 7-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-fluoro-8-methoxy-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-fluoro-8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((1R)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((1R)-1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((1S)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((1S)-1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((dimethylamino)methyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((methylsulfanyl)methoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((R)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((R)-methylsulfinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((R)-methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((S)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 8-((S)-methylsulfinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((S)-methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(1,3-oxazol-2-yl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(2-hydroxypropan-2-yl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(2-methyl-2-oxetanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(2-propanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(3-azetidinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(aminomethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(1-azetidinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(chloromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(difluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(difluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(dimethylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(dimethylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 8-(fluoromethoxy)-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(hydroxymethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(hydroxymethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methoxymethyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methyl-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylsulfanyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylsulfanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 8-(methylsulfinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylsulfonyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-acetyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-amino-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-chloro-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-cyclopropyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-cyclopropyl-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-ethenyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-ethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-ethyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-fluoro-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-imidazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 8-methoxy-2-(trifluoromethyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(4-(3,3,3-trifluoropropyl)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[3-(3,3,3-trifluoropropyl)-1,2-oxazol-5-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[4-(3,3,3-trifluoropropyl)-1H-imidazol-1-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,3-thiazol-2-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-phenyl-1H-pyrazol-3-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-phenyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-propyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(2-phenyl-1,3-oxazol-5-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(3-phenyl-1,2-oxazol-5-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 8-methoxy-3-(4-(2,2,3,3,3-pentafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,3,3-tetrafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-propylphenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(5-propyl-1,2-oxazol-3-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(6-propyl-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,3-triazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[2-(2,2,2-trifluoroethoxy)-1,3-thiazol-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[2-(2,2,3,3,3-pentafluoropropoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[3-(2,2,3,3,3-pentafluoropropyl)-1,2-oxazol-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[4-(2,2,2-trifluoroethoxy)-1,3-thiazol-2-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[5-(2,2,2-trifluoroethoxy)-1,3-thiazol-2-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-{1-[(oxetan-3-yl)methyl]-1H-pyrazol-4-yl}-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-6-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 8-methyl-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,2,4-oxadiazol-3-yl]-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 9-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 9-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; methyl 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylate; methyl(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)carbamyl fluoride; N-(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)acetamide; N-(4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)acetamide; N,N-dimethyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide; N-ethyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide; N-methyl-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide; or N-methyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide. In a third aspect there is provided a compound, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is (2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)-2-methylpropanenitrile; 2-(difluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2,8-dimethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-cyclopropyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-ethoxy-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2-ethyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione; 3-(1-(2,2-difluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(2-fluoro-4-(trifluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione; 3-(4-(2,2-difluoroethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoropropoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 3-(4-(cyclopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide; 7-chloro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((1R)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((1S)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-((dimethylamino)methyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(aminomethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(dimethylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(hydroxymethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(hydroxymethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methoxymethyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 2020391161   25 Nov 2025 8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-amino-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-ethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,3-triazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; or 8-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. In a fourth aspect there is provided a pharmaceutical composition comprising the compound according to any one of the first to third aspects, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable excipient. First, provided herein is A compound of Formula I 2020391161   25 Nov 2025 I or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein CRy, and CRZ is N; 5          wherein Rw is H, halogen, -CN, CO(C । Gkvh. S(O):!(C*: ail-w b. -COOH, -COO(Ci..4alkyl), “CONH2, -CONH(Ci-4aikyl), -CO(diG-4alkylammo), -NH2, G-4alkylammo, diCi-4alkylamino, -NH(COCi-4alkyl), 44(C^alky1)C(=O)F, G^alkyl, Cwdeuteroalkyl, C3-scycloalkyl, Cs^heterocycloalkyL Cj^alkenyl, Cwdeuteroalkoxy, or 5-membered heteroaryl; 10 wherein the Ci-4alkyl and Cj^heterocycloalkyl groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, G-4alkoxy, Goalkyl, -NH2, G-4alkylamino, diG^alkylamino, and -S(O)n(G-4alkyl); Ry is H, F, Cl, -OH, -CN, ( OK , .uikyB. -S(OMG-4alkyl), -COOH, -COO(G-4alkyl), -CONH2, -CONH(Cj-4alkyl), -CO(diCi-4a1kylamino), -NHz, Ci-talkylamino, diCi- 15 4alkylamino, -NH(COCt^alkyl), -N(Ci-4alkyl)C(“O)F, Ci-4alkyl, Cwdeuteroalkyl, C3-scycloalkyi, G^heterocycloalkyl, G-4alkenyl, Ci-4alkoxy, C1-4deuteroalkoxy, or 5-membered heteroaryl; wherein the Cwalkyl, Cs-iheterocycloalkyl, and Cwalkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Ci-4alkoxy, G,.4alkyl, -NH?, Ci 4alkylammo, diCwalkylamino, and -S(O)n(Ci-4alkyl); 20           Rx and Rz are independently H, halogen, -OH, -CN, ~CO(Ci-4alkyi), -S(O)n(Ci- 4alkyl), -COOH, -COO(G-4alkyl), -CONH2, -CONH(Ci-4alkyl), ~CO(diG-4alkylamino), -NH2, Cj-4alkylamino, diCwalkylamino, -NH(COG-4alkyl), -N(Ci-4alkyl)C(=O)F, G-4alkyl, Ci-jdeuteroalkyl, Cs-scycloalkyl, C^heterocycloalkyl, C2-4alkenyl, Cwalkoxy, Ci- 4deuteroalkoxy, or 5-membered heteroaryl; wherein the (Aralkyl, G^heterocycloalkyl. and Ci-4alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cwalkoxy, Ci-jalkyl, -NH2, Chalky!amino, diCMalkylamino, and -S(O)n(Ci-4alkyl); R1 is H, Ci^alkyl, Ci^haloalkyl, or Cwdeuteroalkyl; x is O, NH, or N(Ci-4alkyl): A is independently CH or N, and wherein B is a 5-membered heteroaryl containing one heteroatom selected from N, S, and O and optionally one or two further N atoms, wherein i) B is attached via a C atom to the bicyclic core and R3 is attached via an N atom; or ii) B is attached via an N atom to the bicyclic core and R3 is attached via a C atom; or iii) B is attached via a C atom to the bicyclic core and R3 is attached via a C atom; the 2-benzofuranyl is further optionally substituted with one or two independently selected substituents R3; R3 is CHzCN, C2-6alkyl, Cj-scycloalkyl, Cu3alkoxy, Crealkylamino, diCuealkylamino, -S(O)n(Ci-6alkyl),         -cvcloalkvi). -OOiKCj-scycloalkyl), -NHCH2(C3.5cycloalkyl), - S(O)nCH2(C3-5cycloalkyl), -CH2(C3-5heterocycloalkyl), or phenyl; wherein tire Cwealkyl, C3-scycloalkyl, Ci.3alkoxy, Ci-&alkylamino, diCwdkylamino, -S(O)n(Ci^alkyl), -CH2(C3-scycloalkyl), -OCH2(C3-5cycloalkyl), -NIICH2(C3-5cycloalkyl), and -S(O)HCH2(C3-5cycloalkyi) groups are optionally substituted with 1-9 halogen atoms and are optionally substituted with - -6- CN and wherein the phenyl is optionally substituted with 1-3 substituents selected from halogen, Ci^alkyl, Ci^haloalkyl, C^-alkoxy, and Ci^haloalkoxy; R3 independently is halogen, Cwalkyl, Cwhaloalkyl, Cwalkoxy, or Ci-shaloalkoxy; R4 is Cusalkyl, Cwhaloalkyl, Cuialkoxy, Cwhaloalkoxy, Cj-scycloalkyl, or C3-□cyclohaloalkyl; and n is 0, 1, or 2. Second, provided herein is a pharmaceutical composition comprising a compound of Formula I, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable excipient. Third, provided herein is a compound of Formula 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition as described hereinabove for use in reducing the body weight of a subject or for use in reducing the body-mass-index of a subject. Fourth, provided herein is a compound of Formula 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition as described hereinabove for use in treating a metabolic disorder or tor use in treating a cardiovascular disorder. Fifth, provided herein is a compound of Formula I, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition as described hereinabove for use in treating a metabolic disorder or for use in treating diabetes, obesity, dyslipidemia, or non-alcoholic steatohepatitis (NASH). Reference will now be made in detail to embodiments of the present disclosure. While certain embodiments of the present disclosure will be described, it will be understood that it is not intended to limit the embodiments of the present disclosure to those described embodiments. To the contrary, reference to embodiments of the present disclosure is intended to cover alternatives, modifications, and equivalents as may be included within the spirit and scope of the embodiments of the present disclosure as defined by the appended claims. DETAILED DESCRIPTION Provided herein as Embodiment I i s a compound of Formula I - 7- or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 1) wherein Rw is H, halogen, -CN, -CO(Ct-4alkyl), -S(O)B(Cj-4alkyl), -COOH, -< 00« : ulb B. -CONH2, -CONH(Ci-4alkyl), -CO(diCi4alkylamino), -NH2, Cjwalkylamino, diCi-4alkylamino, -NH(COCi-4alkyl), -N(Ci-dalkyl)C(:=:O)F, Ci.4alkyl, Cwdeuteroalkyl, C3-scycloalkyl, CsJieterocycloalkyl, C2-4alkenyl, Cwdeuteroalkoxy, or 5-membered heteroaryl; wherein the Cj-4alkyl and C3-4heterocycloalkyl groups are optionally substituted with I to 4 substituents independently selected from halogen, -OH, -CN, Ci^alkoxy, Cwalkyl, -NH2, Ci-4alkylamino, diCwalkylamino, and -S(O)n(Ci-4alkyl); R- is H, F, Cl, -OH, -CN, ( 0« 5 .nikyB. -S(OMCMalkyl), -COOH, -COO(C(. 4alkyl), -CONH2, -CONH(Cj-4alkyl), -CO(diCi-4a1kylamino), -NH2, Ci-jalkylamino, diCi-4alkylamino, -NH(COCi.4alkyl), -N(Ci-4alkyl)C(:::O)F, Ci.4alkyl, Cwdeuteroalkyl, C3-scycloalkyl, C3-4heterocycloalkyl, C2-4alkenyl, Ci-4alkoxy, Cwdeuteroalkoxy, or 5-membered heteroaryl; wherein the Chalky!, Cs^heterocycloalkyi. and C^alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Ci-alkow . Cwaikyl, All C Malkylamino, diCMalkylamino,and -S(O)n(Ci-4alkyl); Rx and Rz are independently H, halogen, -OH, -CN, -CO(Ci-4alkyl), -S(O)n(Ci-4alkyl), -COOH, -COO(Ci-4alkyl), -CONH2, -CONH(Ci-4alkyl), -CO(diCi-4alkylammo), -NH2, Ci-4alkylamino, diCi-4alkylamino, -NH(COCi-ialkyl), -N(Ci-4alkyl)C(-O)F, Cwalkyl, Ci->deuteroa1kyl, Cj-scycloalkyl, CsAieterocycloalkyl, C2-4alkenyl, Cwalkoxy, Cj. 4deuteroalkoxy, or 5-membered heteroaryl; wherein the Ci-4alkyl, CjJieterocycloalkyl, and ('■ alkox) groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Ci-4alkoxy, Cwalkyl, -NH2, Ci-4alkylamino, diCi-4alkylamino, and -S(O)n(Ci-4alkyl); R! is H, Ci-4alkyl, Ci-4haloalkyl, or C].4deuteroalkyl; x is O, NH, or X(Ci nlkvi). , or 2-benzofuranyl, wherein A is independently CH or N, and wherein R3;and B is a 5-membered heteroaryl containing one heteroatom selected from N, S, and O and optionally one or two further N atoms, wherein i) B is attached via a C atom to the bicyclic core and R3 is attached via an N atom; or ii) B is attached via an N atom to the bicyclic core and R3 is attached via a C atom; or iii) B is attached via a C atom to the bicyclic core and R’ is attached via a C atom; _ 9 _ the 2-benzofuranyl is further optionally substituted with one or two independently selected substituents R3'; R3 is CH2CN, Cz-ealkyl. Cj-scycloalkyl, Ci-3alkoxy, Ci^alkylamino, diCi-6a1kylamino, 5    -S(O)„(Ci..6alkyl), -CH2(C3.5cycloalkyl), -OCH2(C3.5cycloalkyl), -XIK i HC; wxdoalkv B. - S(O)nCH2(C3-5cycloalkyl), -CH2(C3-5heterocycloalkyl), or phenyl; wherein the C2-&alkyL C3. scycloalkyl, Ci-3a1koxy, Ci-salkylamino, diCi-galkylamino, -S(O)B(Ci-6a1kyl), -CH2(C3. scycloalkyl), -OCHXCj-scydoalkyl), -NHCH2(C3-5cydoalkyl), and -S(O)fiCH2(C3-5cydoalkyl) groups are optionally substituted with 1-9 halogen atoms and are optionally substituted with -10 CN and wherein the phenyl is optionally substituted with 1-3 substituents selected from halogen, Cwalkyl, Ci-jhaloalkyl, Ci-4alkoxy, and Ci-4haloalkoxy; R3 independently is halogen, Cwalkyl, Cwhaloalkyl, Cwalkoxy, or Ci-4haloalkoxy; R4 is Ci-3a1kyl, Cwhaloalkyl, Cwalkoxy, Cwhaloalkoxy, C3-scydoalkyl, or Cj-scyclohaloalkyl; and 15            n is 0,1, or 2. Provided herein as Embodiment 2 is the compound according to Embodiment 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is not 3-(2-(2,2,2-trifluoroethoxy)pyrimidm-5“yl]-2“(trifluoromethyl)-4H,6H,7H,9H- 20    pyrimido[2,1 -c] [ 1,4]oxazin-4-one; 7-(azetidm-l -yl)-3-[ 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazoI-4-yI]-2- (tritluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7-[(dimethylamino)methyl]-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 25            7-chloro-3-[2-(2,2,2 -trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H- pyrido[l,2-a]pyrimidin-4-one; 7-cydopropyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]py rim idi n-4-one; - 10 - 7-fluoro-3-[2-(2,2,2 -trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 7-methoxy-3-[l -(2.,2,3,3,3-pentafiuoropropyl)-lH-pyrazoi-4-yl]-2-(trifluoromethyl)- 4H-pyrimido[ 1,2-b]pyridazin-4-one; 7-metlioxy-3-[2-(2,2;2-trifluoroethoxy)pyrimidin-5-yr|-2-(trifluoroinethyl)-4H- py rimido [ 1,2-b]pyridazin-4-one; 7-metbyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyi)-4H-pyrazinof 1,2-a]pyrimidin-4-one; 7-methyl-3-[2-(2,2,2-triflaoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin~4-one: 8-methoxy-3-[l -(2., 2,3,3,3-pentafluoropropyl)-lH-l, 2,4-triazol-3-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-[3-(2,2,2-tri fluoroethoxy )phenyl]-2-(trifluorornethyl)-4H“pyrido[ 1,2-a]pyrimidin-4-one; or methyl 4-oxo-3-[ 1 -(2,2,3,3,3 -pentafluoropropyl)- IH-pyrazol -4-y 1 ] -2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidme-7-carboxylate. Provided herein as Embodiment 3 is the compound according to Embodiment 1 or Embodiment 2, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound of Formula I is a compound of Formula IA IA. Provided herein as Embodiment 4 is the compound according to Embodiment 1 or Embodiment 2, or a tautomer thereof, or a pharmaceutically acceptable sal t of said compound or said tautomer, wherein the compound of Formula 1 is a compound of Formula IB IB. Provided herein as Embodiment 5 is the compound according to Embodiment 1 or Embodiment 2, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound of Formula I is a compound of Formula IC Provided herein as Embodiment 6 is the compound according to any one of Embodiments 1, 2, 4, and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of 10 said compound or said tautomer, wherein Rw is H,halogen, -CN, ( OK । .rnkybr -S(O)n(Ci-4alkyl), -COXII■. -NH2, Ci-4alkylamino, diCMalkylamino, -NH(COCv4alkyl), -N(Ci-4alkyl)C(=O)F, Chalky!, Cj. 4deuteroalkyl, Cj-scycloalkyl, (X-ralkenyl, Crrdeuteroalkoxy, or 5-membered heteroaryl; wherein the Chalky 1 group is optionally substituted with 1 to 4 substituents independently 15 selected from halogen, -OH, -CN, Cwalkoxy, -NH?, and diCwalkylamino. Provided herein as Embodiment 7 is the compound according to any one of Embodiments 1, 2, 4, and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rw is H, halogen, -CN, -CONH2, -NH2, Ci-4alkylamino, diCwalkylamino, or Ci- 2.0 4denteroalkoxyl; wherein the Ci-4alkyl group is optionally substituted with I to 4 substituents independently selected from halogen, -OH, C^alkoxy, -NH2, and diCwalkylamino. - 12- Provided herein as Embodiment 8 is the compound according to any one of Embodiments 1, 2, 4, and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rw is FI, F, Cl, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -N(CH3)2, - M HCOCI M. A(CH3)C ( O)F. methyl, elhy L -CD- cyclopropyl, -Cl f (M2, ()( D - or 1,3-oxazol-2-yl; wherein the methyl group is optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2, and -N(CH3)2. Provided herein as Embodiment 9 is the compound according to any one of Embodiments 1, 2, 4, and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rw is H, F, Cl, -CN, -CONH2, -NH2, -NHMe, or -OCD3; wherein the methyl group is optionally substituted with 1 to 3 substituents independently selected from F, -OH, methoxy, -NH2, and -N(CH3)2. Provided herein as Embodiment 10 is the compound according to any one of Embodiments 1, 2, 4, and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rw is H, halogen, or Chalky!. Provided herein as Embodiment 11 is the compound according to any one of Embodiments 1, 2, 4, and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rw is H, F, Cl, or methyl. Provided herein as Embodiment 12 is the compound according to any one of Embodiments 1, 2, 4, and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R“ is H. Provided herein as Embodiment 13 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rxis H, halogen, -OH, -CN, -CO(Ci-4alkyl), -S(O)fi(Ci^alkyl), -CONH2, -NH2, Ci-4alkylamino, diCwalkylamino, -NH(COCi-4alkyl), -N(Ci..4alkyl)C(::::O)F, Ci-4alkyl, Cr 4deuteroalkyl, Cs-scycloalkyl, C2-4alkenyl, Ci-4alkoxy, C1-4deuteroalkoxy, or 5-membered - 13 - heteroaryl; wherein the Ci-4alkyl and Cwalkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cwalkoxy, -NH2, and diCi-4alkyiamino. Provided herein as Embodiment 14 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rx is H, halogen, -OH, -CN, -CONH2, -NEL, C walkylamino, diCi-4alkylamino, Ci-4alkoxy, or CMdeuteroalkoxyl; wherein the Chalky] and Ci-4alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, C i.4alkoxy, -NH2, and diCi^alkylamino. Provided herein as Embodiment 15 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rxis H, F, Cl, -OH, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -N(CH3)2, -NH(COCH3), ~N(CH3)C(=:O)F, methyl, ethyl, -CD3, cyclopropyl, -CH=CH2, methoxy, ethoxy, -OCD3, or l,3-oxazol~2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2, and -N(CH3)2. Provided herein as Embodiment 16 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rxis H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy, or -OCD3; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, -OH, methoxy, -NH2, and -N(CH3)2. Provided herein as Embodiment 17 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rx is H, halogen, -OH, -CN, -CO(Ci-(alkyl), -S(O)n(Ci-4alkyl), ~CONH?„ -NH2, Ci-4alkylamino, diCi^alkylamino, -NH(COC]-4alkyl), -N(Ci-4alkyl)C(=O)F, Cj^alkyl, C3-scycloalkyl, C2-4alkenyl, Ct^alkoxy, Cwdeuteroalkoxy, or 5-membered heteroaryl; wherein . 14. the Cwalkyl and Chaalkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Ci^alkoxy.-bM?, and diCi-^alkylamino. Provided herein as Embodiment 18 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rxis H, halogen, -OH, -CN, -CONH2, -NH2, Cwalkylamino, diCwalkylamino, Ci-(alkyl, Ci-(alkoxy, or Cwdeuteroalkoxy; wherein the Cwalkyl and Ci-(alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, Cj. 4alkoxy,-NH2, and di Ci.,(.alkylamino. Provided herein as Embodiment 19 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rxis H, -CN, -NH2, Ci-4alkoxy, or Cr(deuteroalkoxy. Provided herein as Embodiment 20 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R* is H, F, Cl, -OH, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -NH(CH5)2, -NH(COCHj), -N(CH3)C(:=O)F, methyl, ethyl, cyclopropyl, -CH“CH2, methoxy, ethoxy, -OCD3 or l,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 4 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NHj, and -MCIM... Provided herein as Embodiment 21 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rx is H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methyl, methoxy, ethoxy, or -OCD3; wherein the methyl and methoxy groups are optionally substituted with 1 to 4 substituents independently selected from F, -OH, methoxy, -NH?, and -N(CHs)2. Provided herein as Embodiment 2.2 is the compound according to any one of Embodiments 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rx is H, -CN, -NH2, methoxy, or -0(1.) - 15 - Provided herein as Embodiment 23 is the compound according to any one of Embodiments 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -OH, -CN, -CO(Cu4alkyI), -S(O)B(Ci-4alkyl), -CONH2, -NIL, Cu 4alkylamino, diCwalkylamino, -NH(COCi-4alkyl), -N(Cb4alkyl)C(::::0)F, Cwalkyl, Cr 4deuteroalkyl, Cs-scycloalkyl, C2-4alkenyl, Ci^alkoxy, Cw.deuteroalkoxy, or 5-membered heteroaryl; wherein the Ci^alkyl and Cwalkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Ci^alkoxy, -NH?, and diCi-4alkylamino. Provided herein as Embodiment 24 is the compound according to any one of Embodiments 1-22., or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R.y is H, F, Cl, -OH, -CN, -CONFL, -NFL, Ci.4alkylamino, diCi.4alkylamino, Ci. 4alkoxy, or Ci.4deuteroalkoxyl; wherein the Ci-aalkyl and Ci-4alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, Ci^alkoxy, -NH2, and diC1.4alkyla.mino. Provided herein as Embodiment 25 is the compound according to any one of Embodiments 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -OH, -CN, -COMe, SMe. -COXIl ■. -ML -NHMe, -N(CH3)2, -NH(COCHj), -N(CH3)C(=O)F, methyl, ethyl, -CD3, cyclopropyl, “CH=CH?, methoxy, ethoxy, -OCD3, or l,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2,and -N(C H ) -. Provided herein as Embodiment 26 is the compound according to any one of Embodiments 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -OH, -CN, -CONH2, -NHj, -NHMe, methoxy, ethoxy, or -OCD3; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, -OH, methoxy, -NH2, and -N(CH3)2. - 16- Provided herein as Embodiment 27 is the compound according to any one of Embodiments 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -CN, -COO(Cu4alkyI), C[-4alkyl, Cs-scycloalkyl, Ch-rhe terocycloalkyl, or Ci-4alkoxy; wherein the Ci-4alkyl group is optionally substituted with 1 to 4 substituents independently selected from Curalkoxy and diCi-ralkylamino. Provided herein as Embodiment 28 is the compound according to any one of Embodiments 1 -22, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -CN, -COOMe, methyl, cyclopropyl, azetidinyl, or methoxy; wherein the methyl group is optionally substituted with 1 to 3 substituents independently selected from methoxy and dimethylamino. Provided herein as Embodiment 29 is the compound according to any one of Embodiments 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H or Cl. Provided herein as Embodiment 30 is the compound according to any one of Embodiments 1-4 and 6-29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, halogen, -OH, -CN, -CO(Cj-4alkyl), -S(O)n(Ci-4alkyl), -CONHz, -NHz, Ci-4alkylamino, diC Malkylamino, -NH(COC]-4alkyl), -N(Ci-4alkyl)C(=O)F, C]-4alkyl, Cj-4deuteroalkyl, Cj-scycloalkyl, C2-4alkenyl, Ci-4alkoxy, Cwdeuteroalkoxy, or 5-membered heteroaryl; wherein the Cwalkyl and Cwalkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Ci-4alkoxy, -NHz, and diCi-4alkylamino. Provided herein as Embodiment 31 is the compound according to any one of Embodiments 1-4 and 6-29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, halogen, -OH, -CN, -CONH2, -NH2, C]-4alkylamino, diC]-4alkylamino, Ci-4alkoxy, or C^deuteroalkoxyl; wherein the Cwalkyl and Ci-4alkoxy groups are optionally - 17- substituted with 1 to 4 substituents independently selected from halogen, OH, C i.4alkoxy, -NH2, and diCi-4alkylammo. Provided herein as Embodiment 32 is the compound according to any one of Embodiments 1-4 and 6-29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, F, Cl, -OH, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -N(CH3)2, -NH(COCH3), -N(CH3)C(=O)F, methyl, ethyl, -CD3, cyclopropyl, -CH=CH2, methoxy, ethoxy, -OCD3, or l,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2, and -N(CH3)2. Provided herein as Embodiment 33 is the compound according to any one of Embodiments 1-4 and 6-29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, F, Cl, -OH, -CN, -COM f, -NH2, -NHMe, methoxy, ethoxy, or -OCDy wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, -OH, methoxy, -NH2, and -N(CH3)2. Provided herein as Embodiment 34 is the compound according to any one of Embodiments 1-4 and 6-29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H or C1-4alkyl. Provided herein as Embodiment 35 is the compound according to any one of Embodiments 1-4 and 6-29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H or methyl. Provided herein as Embodiment 36 is the compound according to any one of Embodiments 1-4 and 6-29, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H Provided herein as Embodiment 37 is the compound according to Embodiment 1 or Embodiment 2, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound of Formula I is a compound of Formula ID - 18 - ID. Provided herein as Embodiment 38 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -OH, -CN, -CO(C ^alkyl), -S(O)a(CMa1kyl), -CONH2, -NH2, Ci-4alkylamino, diCMalkylamino, -NH(COC]-4alkyl), -N(Ci-4alkyl)C(=O)F, Chalky!, Cj. 4deuteroalkyl, Cj-scycloalkyl, C2-4alkenyl, Ci-^alkoxy, Cwdeuteroalkoxy, or 5-membered heteroaryl; wherein the Cwalkyl and Cwalkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cwalkoxy, -NHz, and diCi-4alkylamino. Provided herein as Embodiment 39 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -OH, -CN, -CONHz, -NH?„ C Malkylamino, diCwalkylamino, Ct-4alkoxy, or Cj^deuteroalkoxyl; wherein the Cwalkyl and Ci-4alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, Cwalkoxy, -NH2, and diCi-4alkylamino. Provided herein as Embodiment 40 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -OH, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -N(CH3)2, -NH(COCHj), -N(CH3)C(=O)F, methyl, ethyl, -CD3, cyclopropyl, -CH=CH2, methoxy, ethoxy, -OCD3, or l,3-oxazoI-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2, and -N(( H 0 . - 19- Provided herein as Embodiment 41 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy, or -OCD3; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, ---OH, methoxy, -NH?, and -N(CH3)2. Provided herein as Embodiment 42 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -CN, -COO(Ci-4alkyl), Chalky!, Cs-scycloalkyl, Cs-dieterocycloalkyl, or C> .alkoxx; wherein the C: alkd group is optionally substituted with 1 to 4 substituents independently selected from < । .alkoxy and di Chalky! amino. Provided herein as Embodiment 43 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R- is H, F, Cl, -CN, -COOMe, methyl, cyclopropyl, azetidinyl, or methoxy; wherein the methyl group is optionally substituted with 1 to 3 substituents independently selected from methoxy and dimethylamino. Provided herein as Embodiment 44 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H or Cl. Provided herein as Embodiment 45 is the compound according to any one of Embodiments 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R2 is H, halogen, -OH, -CN, -CO(Ci.4alkyl), -S(O)a(CMalkyl), -CONH2, -NH2, Ci-4alkylammo, diCi.4alkylamino, -NH(COCi-4alkyl), -N(Ci-4alkyl)C(=O)F, Ci-4alkyl, Ci-4deuteroalkyl, Cj-scycloalkyl, C; alkenyl. C > .alkow . Ci-4deuteroalkoxy, or 5-membered heteroaryl; wherein the Chalky! and Ci-4alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Ci^alkoxy, -NH2, and diCi. 4 alkylamino. - 20 - Provided herein as Embodiment 46 is the compound according to any one of Embodiments 37-44. or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, halogen, -OH, -CN, -CONH2, -NH2, Chalky]amino, diCMalkylamino, Co 4alkoxy, or Ci^deuteroalkoxyl; wherein the Ci.4alkyl and Ci-4alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, Ci-4alkoxy, -NH2, and diCwalkylamino. Provided herein as Embodiment 47 is the compound according to any one of Embodiments 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R' is H, E Cl, -OH, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -N(CH3)2, -NH(COCHj), -N(CH3)C(=O)F, methyl, ethyl, -CD3, cyclopropyl, -CH=CH2, methoxy, ethoxy, -OCD3, or l,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2, and -N(CH 02. Provided herein as Embodiment 48 is the compound according to any one of Embodiments 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy, or -OCD3; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents independently selected from F, -OH, methoxy, -NH2, and -N(CH3)2. Provided herein as Embodiment 49 is the compound according to any one of Embodiments 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, halogen, or Ci^alkyl Provided herein as Embodiment 50 is the compound according to any one of Embodiments 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, F, Cl, or methyl. -21 - Provided herein as Embodiment 51 is the compound according to any one of Embodiments 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H. Provided herein as Embodiment 52 is the compound according to any one of Embodiments 37-51, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R1 is H, methyl, CH?F, or CD3. Provided herein as Embodiment 53 is the compound according to any one of Embodiments 37-51, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R! is II. Provided herein as Embodiment 54 is the compound according to Embodiment 1 or Embodiment 2, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound of formula lisa compound of Formula IE O IE. Provided herein as Embodiment 55 is the compound according to Embodiment 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein x is 0. Provided herein as Embodiment 56 is the compound according to Embodiment 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein x is NH. -22- Provided herein as Embodiment 57 is the compound according to Embodiment 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein x is N(Cj-4alkyl). Provided herein as Embodiment 58 is the compound according to Embodiment 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein x is NCH3. Provided herein as Embodiment 59 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Provided herein as Embodiment 60 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Provided herein as Embodiment 61 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Provided herein as Embodiment 62 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein -23 - Provided herein as Embodiment 63 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R2 is Provided herein as Embodiment 64 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Provided herein as Embodiment 65 is the compound according to any one of Embodiments 1 -58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R2 is             , wherein B is a 5-membered heteroaryl containing two N atoms. Provided herein as Embodiment 66 is the compound according to any one of Embodiments 1-58, 64, and 65, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein B is attached via a C atom to the bicyclic core and R3 is attached via an N atom. Provided herein as Embodiment 67 is the compound according to any one of Embodiments 1-58, 64, and 65, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein B is attached via an N atom to the bicyclic core and R3 is attached via a C atom; Provided herein as Embodiment 68 is the compound according to any one of Embodiments 1-58, 64, and 65, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein B is attached via a C atom to the bicyclic core and R3 is attached via a C atom. Provided herein as Embodiment 69 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein -24- Provided herein as Embodiment 70 is the compound according to any one of Embodiments 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Provided herein as Embodiment 71 is the compound according to any one of Embodiments 1 -58, or a tautomer thereof, or a pharmaceutically acceptable salt of said 10 compound or said tautomer, wherein R2 is 2-benzofuranyl. Provided herein as Embodiment 72 is the compound according to any one of Embodiments 1-71, or a tautomer thereof, or a pharmaceutically acceptable salt of said 15 R2 or the 2-benzofuranyl is further optionally substituted with one substituent R3. Provided herein as Embodiment 73 is the compound according to any one of Embodiments 1-71, or a tautomer thereof, or a pharmaceutically acceptable salt of said R3 or the 2-benzofuranyl is not further substituted with one or two independently selected 20 substituents R3. -25 - Provided herein as Embodiment 74 is the compound according to any one of Embodiments 1-70, 72, and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R' is C2-6alkyI, Cusalkoxy, -CHz^-scycloalkyl), -OCHzCCs-scycloalkyl), or phenyl; wherein the Chalky!, ( । nikoxy. -CH^Cs-scycloalkyl), and -OCHiCCs-scycloalkyl) groups are optionally substituted with 1 to 5 halogen atoms and are optionally substituted with -CN and wherein the phenyl is optionally substituted with one halogen substituent. Provided herein as Embodiment 75 is the compound according to any one of Embodiments 1-70, 72, and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R' is ('■ mlkyi. Cl adkovw or -OCHzfCvscycloalkyl); wherein the C2-salkyl, Ci-3alkoxy, and -OCHz^.scycloalkyl) groups are optionally substituted with 1 to 5 halogen atoms and are optionally substituted with -CN. Provided herein as Embodiment 76 is the compound according to any one of Embodiments 1-70, 72, and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R3 is Cz-salkyl or Cj-salkoxy; wherein the C2-6alkyl and Cj.jalkoxy groups are optionally substituted with 3-5 halogen atoms. Provided herein as Embodiment 77 is the compound according to any one of Embodiments 1-70, 72, and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein RJ is 2,2,2-trifluoroethyl, propyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 2,2,3,3,3-pentafluoropropyl, -OCH2CN, -OQCHs^CN, difluoromethoxy, tri fluoromethoxy, -OCH(CN)CH?, 2.-fluoroethoxy, 2,2,-difluoroethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoropropoxy, 2,2,3,3-tetrafluoropropoxy, 2,2,3,3,3-pentafluoropropoxy, cyclopropylmethyl, (2,2-difluorocyclopropyl)methyl, (3,3-difluorocyclobutyl)methyl, cyclopropylmethoxy, (2,2-difluorocydopropyl)methoxy, phenyl, 3-fluorophenyl, or 4-fluorophenyl. Provided herein as Embodiment 78 is the compound according to any one of Embodiments 1-70, 72, and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein -26- R3 is 2,2-difluoropropyl, 4,4,4-trifluorobutyl, 2,2,3,3,3-pentafhroropropyl, -OQCHOzCN, trifluoromethoxy, -OCH(CN)CHj, 2-fluoroethoxy, 2,2,-difluoroethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoropropoxy, cyclopropylmethoxy, or (2,2-di fluorocyclopropyl )methoxy. Provided herein as Embodiment 79 is the compound according to any one of Embodiments 1-70, 72, and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R3 is 2,2,3,3,3-pentafluoropropyl or 2,2,2-trifluoroethoxy. Provided herein as Embodiment 80 is the compound according to any one of Embodiments 1-72 and 74-79, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R3 independently is halogen or Chalky!. Provided herein as Embodiment 81 is the compound according to any one of Embodiments 1-72 and 74-79, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R3 is For methyl. Provided herein as Embodiment 82 is the compound according to any one of Embodiments 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is Cmalkyi, CMhaloalkyl, Ci-4alkoxy, or Cs-scycloalkyl. Provided herein as Embodiment 83 is the compound according to any one of Embodiments 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is Ci-shaloalkyl. Provided herein as Embodiment 84 is the compound according to any one of Embodiments 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is methyl, ethyl, fluoromethyl, di fluoromethyl, trifluoromethyl, methoxy, ethoxy, or cyclopropyl. -27 - Provided herein as Embodiment 85 is the compound according to any one of Embodiments 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy, or cyclopropyl. Provided herein as Embodiment 86 is the compound according to any one of Embodiments 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is trifluoromethyl. Provided herein as Embodiment 87 is the compound according to any one of Embodiments 1-86, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein n is 0. Provided herein as Embodiment 88 is the compound according to any one of Embodiments 1 -86, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein n is 1. Provided herein as Embodiment 89 is the compound according to any one of Embodiments 1-86, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein n is 2. Provided herein as Embodiment 90 is the compound according to Embodiment 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is (2R)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-3-yl)phenoxy )propanenitrile; (2R?y2-(4-(8-methoxy-4-oxo-2~(trifluoromethyl)-4H-pyrimido[l,2-a]pynmidin-3-yl )phen oxy)propanen itrile; (2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[l ,2-a]pyrimidin-3-yl)phenoxy)propanenitrile; -28 - (2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrimido| l,2-a]pyrimidin-3-yl)phenoxy)propanenitrile; (4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-3-yl)-lH-pyrazol -1 -y 1 )acetonitril e; (4-( 8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-3 -yl)phenoxy)acetonitrile; (4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-3-yl)phenyl laceton itrile; (4-(8-methoxy-4-oxo-2-(triflnorometliyl)-4H-pyrimido[l;2-a]pyrimidin-3-yl)phenoxy jacetonitrile; (4-oxo-3-(1 -(2,2,3,3,3 -pentafluoropropyl)- IH-pyrazol -4-yl )-2-(trifluorom ethyl)-4H-pyrido[l,2-a]pyrimidin-8-yl)acetonitrile; l-(chloromethyl)-7-[ l-(2;2,3,3;3-pentafluoropropyl)-lH-pyrazol-4-yl]-8-(trifluoroniethyl)-lH,2H,6H-pyrimido[l,2-a][l,3]diazine-2,6-dione; l-(fluoromethyl)-7-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-8-(trifluoromethyl)-lH,2H,6H-[l,3]diazino[l,2-a]pyrimidine-2,6-dione; 1-(methyl-ds)-? -(4-(2,2,2-trifluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyrimido[ 1,2-a]pyrimidine-2,6( 1H)-dione; l-methyl-7-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-8-(trifluoromethyl)- 1 H,2H,6H-[ 1,3]diazino[ L2-a]pyrimidine-2,6-dione; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-3-yl)phenoxy)-2-methylpropanenitrile; 2-(4-(8-methoxy-4~oxo-2-(tnfluorometiiyl)-4H-pyrido[l,2-a]pyrimidin-3-yl)phenoxy)propanenitri le; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrimido[l,2-a]pyrimidin-3-yl)phenoxy )propanenitrile; 2-(difluoromethyl)-3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-4H-pyridofl ,2-a]pyrimidm-4-one; 2-(difluoromethyl)-4-oxo-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-4H-pyridofl, 2-a]pyrimidine-8-carbonitrile; -29- 2-(difluoromethyl)-8-methoxy-3-(l-(3,3,3-triflaoropropyl)-lH-pyrazol-4-yl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 2-(difluoromethyl)-8-methoxy-3~(l-(4,4,4~trifluorobutyl)-lH-pyrazol-4-yl)-4H-pyrido[l,2-a]pyrimidin-4-one; 2-(difluorornethyl)-8-methoxy-3-(4-(2,2,2-tri fluoroethoxy )phenyl)-4H-pyrido[l,2-a]pyrimidin-4~one; 2~(dsfluoromethyl)-8-methoxy-3-(6-(2,2,2-trifluoroetboxy)-3-pyridsnyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 2-(fluoromethyl)-4-oxo-3-(l-(2,2,3,3,3-pentaflaoropropyl)-lH-pyrazol-4-yl)-4H-pyrido[l,2-a]pyrimidine-8~carbomtnle; 2-(fluoromethyl)~8-metboxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[l,2-aJpyrimidm-4-one; 2-(tritluoromethy 1)-3 -[ 1 -(3,3,3 -trifluoropropyl)-1 H-pyrazol-4-yl] -4H,6H, 7H,9H-pyrimido[2,l-c] [ l,4]oxazm-4-one; 2,8-dimethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[l 3~a]pyrimidin~4-one; 2-cyclopropyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 2-e±oxy-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 2-ethoxy-8-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-4H-pyrido[l,2-a]pyrimidin-4-one; 2-ethyl-8~methoxy -3-(1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-4H-pyrido[l,2-a]pyrimidin-4-one; 2~ethy1-8~methoxy-3-(4-(2,2,2-trifhioroethoxy)phenyl)-4H-pyrido[l,2-a]pyrimidin-4~ one; 2-ediyl-8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-4H-pyrido[l,2-a|py rimidin-4-one; 3-(1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazoi-4-yl)-2-(trifluororaethyl)-4H- pyrido[l ,2-a]pyrimidine-4,8( lH)-dione; 3-( 1-(2,2-difluoropropyl)“lH-pyrazol-4-yl)-8-inethoxy-2-(trifiuoromethyl)-4H“ pyrido[l,2-a]pyrimidin-4~one; - 30 - 3-(l-(3-fluorophenyl)-lH-pyrazol-4-yl)-8-metiioxy-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 3-(l-(4-fluoropheny1)-lH-pj'razol-4-y1)-2-(trifluorometiiyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 3-(l-(4-fluorophenyl)-lH-pyrazol-4-yl)-8-inethoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4~one; 3-(l-{[(lR)-2,2-difluorocyclopropyl]methyl}-lH-pyrazol-4-yi)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 3-(l-{[(lS)-2,2-difluorocyclopropyl]methyl}-lH-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 3-(l-benzofuran-2-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pj,rimidin-4-one; 3-(l-cyclopropyl-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 3-(1 -cyclopropyl- lH-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l, 2-a]pyrimidin-4-one; 3-(1 -phenyl-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one; 3-(l-propyl-lH-pyrazol-4“yl)-2“(trifluoromethyi)-4H-pyrido[l,2-a]pyrimidin-4-one; 3-(2-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyridofl ,2-a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2;2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pynmidin-4-one; 3~(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifhoroinethyl)-4H-pyridofl, 2-a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-meflioxy-2-(trifluoroniethyl)-4H-pyrimido[l,2-a]pyrimidin-4-one; 3-(2-fluoro~4-(trifluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 3-(2-fluoro-6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-8-methoxy-2-(trifluoromethyl)-4H-pyridofl,2-a]pyrimidin-4-one; -31 - 3-(3-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 3-(3~fluoro~4-(2,2,2~trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyridofl ,2-a]pyrimidin-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H- pyrimido[l,2-a]pynmidin-4~one: 3-(4-((( lR)-2,2-di fluorocyclopropyl)methoxy)phenyi)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 3-(4-((( 1 S)-2,2-difl uorocyclopropyl)inethoxy)phenyl)-8-methoxy-2 -(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 3-(4-((2,2~difluorocyclopropyl)methoxy)pbenyl)~8-methoxy-2-(trifluoromethyl)-4H~ pyrido[l,2-a]pyrinudin-4-one; 3-(4-(2,2,2-triflaoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido|l,2-a]pyrimidm-4-one; 3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine- 4,8(lH)-dione; 3-(4-(2,2,2-trifluoroetiioxy)phenyl)-2,8-bis(triflaoromethyl)-4H-pyrido[ 1,2-a]py rimidin-4-one; 3-(4-(2,2~difluoroethoxy)~2-fluoropbenyl)~8-methoxy-2Xtrifluoromethyl)-4H~ pyrido[l,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoroethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 3-(4-(2,2-difluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidm-4 -one; 3-(4-(2,2-difluoropropoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 3 -(4-(2-fluoroethoxy)phenyl)-8 -(methyloxy-d?) -2 -(tnfluoromethyl) -4H-pyrido [ 1,2-a]pyrimidin~4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrimido[l,2-a]pyrimidin-4-one; - a2 - 3 -(4-(2-fluoroethoxy)pheny 1)-8 -methoxy-2-(trifl aoromethyl )-4H-pyrido [ 1,2-a]pyrimidm-4-one; 3-(4~(2-fluoroethoxy)pheByl)-8-methoxy-2~(trifluoromethyl)-4H-pyrirnido[l,2-a]pyrimidin-4-one; 3-(4-(8-m ethoxy-4 -oxo-2-(trifluoromethyl)-4H-pyrido(l,2-a]pyrimidin-3-yl)-lH-py razoi-1 -y l)propanenitrile; 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyi)~4H-pyrido[l,2-a]pyrimidm-3-yl)phenyl )propanenitrile; 3-(4-(cyclopropyhnethmy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido ( 1,2-a]pyrimidin-4-one; 3-(4~(cyclopropylmethoxy)phenyd)-8-(methyloxy-d3)-2~(trifluoromethyl)~4H-pyrido[l ,2-a]pyrimidin-4-one; 3-(4-(cydopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido(l,2-a]pyrimidin-4-one; 3-(4-(cyclopropylm ethoxy )phenyl)-8~metboxy~2-(trifluoromethyl)-4H-pyrimido[l, 2-a]pyrimidin-4-one; 3-(4-(difluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a|py rimidin-4-one; 3-(5-(2,2,2-trifluoroethoxy)-2-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 3-(5-fluoro-6-(2,2,2-trifluoroethoxy )-3-pyridinyl)-8-methoxy-2-(triflaoromethyl)-4H-pyrido[l,2-a]pyrimidin-4~one: 3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyi)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidm-4 -one; 3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-( tri fluoromethyl)-4H,6H,7H,9H-pyrimido[2,1 -c] [ 1,4]oxazin-4-one; 3-(1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrazinof 1,2-a]pyrimidin-4-one; 3-[ 1-(2,2,3,3,3-pen tafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; -33 - 3-[l-(cyclopropylmethyl)-lH-pyrazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 3-[l~(cyclopropy1methyl)4H-pyrazol~4-yl]~8-methyl-2-(trifluoromethyl)-4H~ pyrimi do [ 1,2-b]pyridazin -4-one; 3-[5-iodo-l-(2,2,3,3,3-pentafluoropropyi)-lH-l,2,3-triazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 3-{l-[(2,2-difluorocyc1opropyi)methyl]-lH-pyrazol-4-yl}-7-fluoro-8-metboxy-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 3-{ l-[(2,2-difluorocyclopropyl)methyl]-lH-pyrazol-4-yl}-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 3-{l~[(2.,2-difluorocyclopropyl)methy1]-lH-pyrazol-4~y1}-8-methyl-2-(trifluorom ethyl) -4H-pyrim ido [ 1.2 -b] pyridazin-4-on e; 3-{l-[(353-difluorocyclobutyl)methyr|-lH-pyrazol-4-yl}-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 3-{l-[(3,3-difluorocyc1obutyl)mefhyl]-lH-pyrazol-4-yl}-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[l ,2-b]pyridazin-4-one; 3-{ l-[(3,3-difluorocyclobutyl)methyl]-lH-pyrazol-4-yl}-8-methyl-2-(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one; 3-fluoro-l-methyl-7-[l-(2,23A3i3entafluoropropyl)-lH-pyrazo1-4-yl]-8-(trifluoromethyd)-lH,2H;6H-

[13] diazino[l,2-a]pyrimidine-2,6-dsone; 4-oxo-3-(l-(23,3;3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carbomtrile; 4-oxo-3-(l -(2., 2,3.3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxylic acid; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carbonitrile; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(tnfluoromethyl)~4H-pyrido[l,2-a]pyrimidine-8-carboxamide; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxylic acid; ..34.. 4-oxo-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyI)-4H-pyrido [ 1,2-a]py rimidine -7 -carbonitrile; 7-(1-(2,2,3,3,3~pentafluoropropyl)-rH-pyrazol-4-yl)-8-(trifluoromethyl)-2H-pyrimido[l,2-a]pyrimidine-2,6(lH) -dione; 7-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyrimido[l,2-a]pyrimidine-2,6(lH)-dione; 7-(4-(2,2,2-trifluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyrimido[l .,2- a] py rim! dine -2,6 (1H)-di one; 7-(4-(2-fluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyrimido[l,2-a]pyrimidme-2,6(lH)-dione; 7-(methoxymethyl)~3-[l -(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7,8-dimethyl-2-(tnfluoromethyl)-3-[l-(3,3,3-trifluoropropyl)-lH-pyrazol-4-yl]-4H-py rimido [ 1,2-b]pyridazin-4-one; 7,8-dimethyl-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one; 7,9-dimethyl-3-[ 1 -(2,2,3,3,3 -pentafluoropropyl)-1 H-pyrazol-4-yl] -2 -(trifluoromethyl)-4H-pyrazino[l,2-a]pyrimidin-4-one; 7-chloro-2-(trifluoromethyl)-3-[] -(3,3,3-trifluoropropyl)-lH-pyrazol-4-yl]-4H-pyrido[l,2-a]pyrimidin-4-one; 7-chIoro-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-( trifluoromethyl)- 4H-pyrazino [ 1,2-a]pyrimidin-4~one: 7-cbloro-3-[l-(2,2,3,3,3-pentafluoropropyi)-lH-pyrazol-4-yi]-2-(trifluoromethyl)-4H-pyri do [ 1,2-a] pyrim idin -4-one; 7-chloro-8-methoxy-2-(trifluoromethyl)-3-[l-(3,3,3-trifluoropropyl)-lH-pyrazol-4-yl] -4H-pyrido [ 1,2-a]py rimidin-4-one; 7-chloro-8-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-[l,3]diazmo[l,2-a]pyrirnidin-4~one; 7-chloro-8-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one; - 35 - 7-chloro-8-methyi-2-(trifluororriethyl)-3-[l-(3,3,3-trifluoropropyl)-lH-pyrazoi-4-yl]-4H-pyrido [ 1,2-a]pyrimidin-4-one; 7 -chloro-8-methyl-3-[ 1 -(2,2,3.3,3 -pentafluoropropyl)-1 H-pyrazol~4-yi] -2 -(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7 -chloro-8-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl ] -2-(trifluoromethyl)-4H- pyrido[l,2-a]pyrimidin-4~one: 7-cyclopropyl-2-(trifluorometbyl)-3-[l~(3,3,3-trifluoropropy1)-lH~pyrazol-4-y1]-4H-pyrido[l,2-a]pyrimidin-4-one; 7-cyclopropyl -3 -[ 1 -(2,2,3,3,3 -pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 7-fluoro-2~(trifluoromethyl)-3-[l-(3,3,3-trifliioropropyl)-lH-pyrazol-4~yl]-4H-pyrido[l,2-a]pyrimidin-4-one; 7-fluoro-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4~one: 7~fluoro-8-hydroxy-3-[l~(2,2,3,3,3-pentafhioropropyi)~lH-pyrazol~4-yi]~2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7-fluoro-8-methoxy-2-(trifluoromethyl)-3-[l-(3,3,3-trifIuoropropyl)-lH-pyrazol-4- yl] -4H~pyrido [ 1,2-a|py rimidin-4-one: 7-fluoro-8-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-[l,3]diazino[l,2-a]pyrimidin-4-one; 7-fluoro-8-methoxy-3-[ 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazoI-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7~fluoro-8-methoxy-3-[4~(2,2,2-trifluoroethoxy)phenyl]-2~(trifkioroiT!etbyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7-fluoro-8-methyl-3-[ 1-(2,2,3,3,3-pentafluoropropyl)-l H-pyrazol-4-yl]-2-(Mfluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7-niethoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-[l,3]diazmo[l,2-a]pyrimidin-4-one; 7-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrazino [ 1,2-a ]pyrimidin-4-one; - 36 - 7-inethoxy-3-[l-(2,2,3,3,3-pentaflaoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 7 -methyl -2-(trifhioromethyl)-3-[ 1 -(3,3.3 -tri fluoropropyl)- IH-pyrazol -4-yl] -4H-pyrimi do [ 1,2-b]pyridazin -4-one; 7-metiiyl-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H- [1,3] diazino [ 1,2-a] pyrimidin-4-one; 7-methyl-3-[l-(2,2,3,3,3-pentafluoropropy1)-lH-pyrazol-4-y1]-2-(trifluorom ethyl)-4H-pyrazino [ 1,2-a]pyrimidin-4-one; 7-methyl-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 7 -methyl -3 - [ 1 -(2,2,3,3,3 -pentafl u oropropyl) -1 H-pyrazol-4-yl] -2Xtri fluoromethyl) -4H-pyrimido[ 1,2-b]pyridazin -4-one; 8-((lR)-l-hydroxyethyl)-3-( 1-(2,2,3,3,3-pentafluoropropyl)“lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-((lR)-l-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-((1 S)-l -hydroxyethyl)-3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-((lS)-l-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-((dimethylamino)methyl)-3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methyloxy-d3)“2-(trifiuoromethyl)-3~(l-(3,3,3~trifluoropropyl)“lH-pyrazol“4-yl)-4H-pyri do [ 1,2-a]pyrim idin -4-one; 8-((methylsulfanyI)methoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidm-4-one; 8-((R)-ethylsulfinyl)-3-(4~(2,2,2-tnfluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l ,2-a]pyrimidm-4-one; 8-((R)-methylsulfinyl)-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one; 8-((R)-methylsulfinyl)-3-(4-(2,2,24rifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-((S)-ethylsu1finyl)-3-(4-(2,2,2-trifluoroetiioxy)phenyl)-2-(trifluoromethy1)-4H-pyridofl ,2-a]pyrimidin-4-one; 8-((S)-methylsulfinyl)-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 8-((S)-methylsu1finyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyridofl, 2-a]pyrimidin-4-one; 8-(l,3-oxazoi-2-yl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(tritltioroniethyl)"4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-(l-hydroxyethyl)-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(l-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H- pyridof 1,2-a]pyrimidin-4~one: 8~(2-hydroxypropan-2-yl)-3-[l~(2,2,3,3,3~pentafluoropropyl)-]H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 8-(2-methyl-2-oxetanyl)-3-(4-(2;2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-(2-propanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyridofl ,2-a]pyrimidin-4-one; 8-(3-azetidinyl)-3-(4-(2;2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H- pyridof 1,2-a]pyrimidin-4~one: 8~(aminomethyl)~3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazd-4-yl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 8-(1-azetidinyl)-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(tritluoromethyl)“4H-pyrido[ 1,2-a]pyrimidm-4-one; 8-(chloromethoxy)-3-[l~(2,2,3,3,3~pentafluoropropyl)-lH~pyrazol~4-yl]-2-(trifluororaetbyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(chloromethoxy)-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yI]-2-(trifluoromethyl)-4H-pyrimido[ l,2-b]pyridazin-4-one; -38- 8-(difluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(triflaoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-(difluoromethyl)-3-(4~(2,2,2-tnfluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(dimethylamino)-3-(l-(2,2,3,3,3-pentaflaoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(dimethylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyi)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(ethylsulfinyl)-3-(4-(2,2,2-triiluoroethoxy)pheiiyl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-(fluoromcthoxy)-2~(trifluorometbyl)-3-(l~(3,3,3-trifluoropropyl)-lH~pyrazol-4~yl)-4H-pyrido[l ,2-a]pyrimidin-4-one; 8-(fluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(triflaoromethyl)-4H- pyrido[ 1,2-a]pyrimidin-4~one: 8-(fluoromethoxy)-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazoi-4-yl]-2-(trifluoromethy])-4H-pyrido[ 1,2-a]pyrimidin-4-one; 8-(fluoromethoxy)-3-[ 1-(2,2,3,3,3-pentafluoropropyl)4H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one; 8-(fluoromethyl)-3-(l -(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(tluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyi)-2-(tritluoromethyl)-4H- pyrido[ 1,2-a]pyrimidin-4~one: 8~(hydroxyiTKdhyl)-3-( 1-(2,2,3,3,3~pentafluoropropyl)~rH~pyrazol~4-yl)~2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-oue; 8-(hydroxymethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methoxymethyl)-3- [ 1 -(2,2,3,3,3 -pentafluoropropyl)- lH-pyrazol-4-yl ] -2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 8-(methylamino)-3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2 -(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one; -39- 8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-(methylamino)-3-(4-(2.,2,2-trifiuoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[l ,2-a]pyrimidin-4-one; 8-(methyl-d3)-3-(4-(2;2,24riflaoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methyloxy-d s)-3 -(1-(2,2.3,3,3 -pentafluoropropyl)- IH-pyrazol -4-y1)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-( 1-(2,2,3,3,3-pentafl aoropropy 1)-lH-pyrazol-4-y 1)-2-(trifluoroniethyl)-4H-pyrimido[l,2-a]pyriniidin-4-one; 8-(methyloxy-d3)-3-( 1-(4,4,4~trifiuorobutyl)-iH-pyrazol-4-yl)-2-(tri fluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(4-(2,2;2-trifluoroethoxy)phenyl)-2-(trifluoromethyI)-4H- pyrido[ 1,2-a]pyrimidin-4~one: 8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido [ 1,2-a] py rim idin-4-one; 8-(methyloxy-d3)-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methylsulfanyl)-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluorometbyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methylsulfanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methydsulfinyl)-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2- (trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 8-(methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifiuoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methylsulfonyl)-3-(4-(2,2,2-trifluoroethoxy)phenyi)-2-(tnfluoromethyl)-4H-pyrido[l ,2-a]pyrimidm-4-one; 8-acetyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; - 40 - 8-amino-3-( 1-(2,2,3,3,3-pentafluoropropyl)- lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-amino-3-(4-(2,2,2-triflaoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido|l,2-a]pyrimidin-4-one; 8-cbloro-3-(l-(2,2,3,3,3-pentafluoropropyi)-lH-pyrazol-4-yi)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a] pyrim idin -4-one; 8-chloro-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]py rimidin-4-one; 8-cyclopropyl-3-(4~(2,2,2-trifluoroethoxy)phenyl)-2~(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-cyclopropyl-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-ethenyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2~(tnfluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-etiioxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]py rimidin-4-one; 8-etbyl-3-(4-(2,2,2.-tri fluoroethoxy )phenyl)-2-(tnfluoromethyl)~4H-pyrido[l,2-aJpyrimidsn-4-one; 8-fluoro-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8~hydroxy~3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4~yl]-2~(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(]-(3-(trjfluoromethyl)phenyl)-lH-pyiazol-4-yl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(l-(3,3,3-trifluoropropyl)-lH-imidazol-4-yl)-4H-pyrido[l ,2-a]pyrimidm-4-one; 8-methoxy-2-(trifluoromethyl)-3-(l-(3,3,3-trifluoropropyl)-lH-pyrazol-4-yl)-4H-pyrido[l,2-a]pyrimidin-4-one; -41 . 8-methoxy-2 -(trifl uoromethyl)-3-(1 -(3 3,3 -trifluoropropyl)-1 H-py razol-4-yl)-4H-pyrimido[l,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluorome±yl)-3-(l-(4-(trifluorometiiyl)phenyl)-lH-py'razol-4-yl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-niethoxy-2-(trifluoromethyl)-3-(4-(3,33-trifluoropropyl)phenyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8~methoxy~2-(trifluoromethyl)-3-[l -(33,3~trifluoropropyl)~lH-pyrazo!-4-yl]-4H-pyrimido[l,2-b]pyridazin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[3-(3,3,3-trifiuoropropyl)-l,2-oxazol-5-yr|-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methoxy-2-(trifluorome±yl)-3 - [4-(3,3 3 -tri fluoropropy!)- IH-imidazol -1 -y1 ] -4H-pyrido[l,2-a]pyrimidin-4-one; 8-niethoxy-2-(trifluoromethyl)-3-[5-(3,33-trifluoropropyl)-l,3-thiazol-2-yl]-4H- pyrido[l,2-a]pyrimklin-4~one: 8-methoxy-2-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)4H-pyrido[l,2-a]pyrimidm-4-one; 8-inethoxy-3-(l-(2,2,2-trifluoroethyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methoxy-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)- 4H-pyrido[ 1,2 -a] pyrimi din-4-one; 8-methoxy-3-(l-(2,23,33-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)- 4H-py rimido [ 1,2-a]pyrimidin-4-one: 8~meflioxy~3-(l-(4,4,4-trifluorobutyl)-lH~pyrazol-4~yl)-2~(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8~m ethoxy-3 -(1 -(4,4,4-trifl uorobutyl)- IH-pyrazol -4-yl )-2-(trifluorom ethyl)-4H-pyrimido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(1-phenyl-1 H-pyrazol-3-yl)-2~(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methoxy-3-( 1 -phenyl -IH-pyrazol -4-yl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidm-4-one; -42- 8-methoxy-3-(l-propyl-lH-pyrazol-4-yl)-2-(trifluoroinethyl)-4H-pyrido[ 1,2- a]pyrimidm-4-one; 8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H~ pyridofl ,2-a]pyrimidin-4-one; 8-medioxy-3-(2-phenyl-l,3-oxazol-5-yl)-2-(trifluoromethyl)-4H-pyrido[l,2- a]pynmidin-4-one; 8~methoxy~3-(3-phenyl-l,2-oxazol-5-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,2-tnfiuoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-medioxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[ 1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,3,3,3-pentafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,3,3-tetrafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(trifluoromethoxy)pheny1)-2-(trif]uorome1hyl)-4H-pyrido[l,2-aJpyrimidsn-4-one; 8-medioxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[ 1,2-a]pyrimidin-4-one; 8~methoxy~3-(4-propylphenyl)-2Xtrifluoromethyl)-4H~pyrido[l,2~a]pyrimidin-4-one; 8-methoxy-3-(5-propyl-l,2-oxazol-3-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridmyl)-2-(trifluoromethyl)-4H-pyrimido[l,2-a]pyrimidin-4-one; 8-metlioxy-3-(6-propyl-3-pyridinyl)-2-(trifluoroinethyl)-4H-pyrido[l,2-a]pyrimidin- 4-one; -43 - 8-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-l,2,3-triazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8 -methoxy-3 -(1-(2,2,3,3,3 -pentafluoropropyl) -1 H-pyrazol-3 -y 1] -2. -(trifluoromethyl) -4H-pyrido[l ,2-a]pyrimidin-4-one; 8-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)- 4H-[ 1,3]diazino[ 1,6-a]pyrimidm-4-one: 8~methoxy~3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4~yl]-2~(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one; 8-methoxy-3-|2-(2,2,2-trifluoroethoxy)-l,3-thiazol-5-yl]-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methoxy-3-[2-(2,2,2~tnfluoroethoxy)pyrimidin-5~yl]~2-(trifluoromethyl)-4H- [1,3]diazmo[l ,2-a]pyrimi din-4-one; 8-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrinridin-5-yl]-2-(trifluoroinethyl)-4H-pyrido[l,2-a]pyrimidin-4~one; 8-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)~4H-pyrimido[l,2-b]pyridazin-4-one; 8-methoxy-3-[2-(2,2,3,3,3-pentafluoropropoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-[3-(2,2,3,3,3-pentafluoropropyl)-l,2-oxazoi-5-yi]-2-(trifluoromethyl)-4H-py rido[ 1,2 -a] pyrimi din-4-one; 8-methoxy-3-[4-(2,2,2-tri fluoroethoxy)-!, 3-thiazoi-2-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4~one; 8~methoxy~3-[5-(2,2,2-trifluoroethoxy)-] ,3-thiazol-2-yl]-2-(trifluoromethyl)-4H~ pyrido [ 1,2-a]py rim idin-4 -one; 8-methoxy-3-{l-[(oxetan-3-y1)methyl]-lH-pyrazol-4-yl}-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-6-methyl-3-[ 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluorometbyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 8-methyl-2-(trifluoromethyl)-3-[l-(3,3,3-trifluoropropyl)-lH-pyrazol-4-yl]-4H-py rimido [ 1,2-b]pyridazin-4-one; .44. 8-methyl-2-(triflaorometiiyl)-3-[5-(3,3,3-trifluoropropyl)-l,2,4-oxadiazol-3-yl]-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methyl-3-[l -(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H,6H, 7H,8H,9H-pyrimido[ 1,2-a|pyrazm-4-one; 8-mefliyl-3-[l-(2,2,3,3,3-pentafluoropropy1)-lH-py'razol-4-y1]-2-(trifluorom ethyl)-4H-pyrimido[l,2-b]pyridazin-4-one; 8-methyl-3-[2-(2,2,2-triflaoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrmiido[l,2-b]pyridazin-4-one; 8-methyl-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrimido[l,2-b] pyridazin-4-one; 9-chloro-8-methoxy-3-[ 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 9-fluoro-8-methoxy-3-[ 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 9-methyl-3-[ 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrazino [ 1,2-a]pyrimidin-4-one; methyl 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-aJpyrimidme-8-carboxylate; methyl(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-y 1)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-8-yl)carbamyl fluoride; N-(4-oxo-3~(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluorom 4H-pyri do [ 1,2-a] pyrim idin -8 -yl )acetam ide; N-(4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-8-yl)acetamide; N,N-dimethyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluofomethyl)-4H-pyrido[l,2-a]pyrimidme-8-carboxamide; N-ethyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxamide; - 45 - N-methyl-4-oxo-3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxamide; or N-methyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-py rido [1,2 -a]pyrimidine-8-carboxami de. Provided herein as Embodiment 91 is the compound according to Embodiment 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is (2R)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyI)-4H-pyrimido[l,2-a]pyrimidin-3-yl)phenoxy )propanenitrile; (2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-3-y 1 )phenoxy)propanen itrile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[l.,2-a]pyrimidin-3-yl)phenoxy)-2-methylpropanenitrile; 2-(difluoromethyl)~8-methoxy-3-(4~(2,2,2-tri fluoroethoxy )phenyl)-4H-pyrido[l,2-a]pyrim idin-4 -one; 2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 2,8-dimethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[l,2-a]pyrmiidiii-4-one; 2-cyclopropyl-8-methoxy-3-(4-(2,2,2~trifhioroethoxy)phenyl)~4H-pyrido[l,2-a]pyrimidin-4-one; 2-ethoxy-8-methoxy-3-(4-(2,2,2-tritluoroethoxy)phenyl)-4I-l-pyrido[l,2-a]pyrimidin-4-one; 2~ethyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[l,2-a.]pyrimidin-4-one; 3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-4,8(lH)-dione; 3-(l-(2,2~difhioropropyl)-lH~pyrazol~4~yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l ,2-a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2,2-tri fluoroethoxy )phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; -46- 3-(2-fiuoro-4-(trifluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido f 1,2-a]pyrimidin-4-one; 3-(3~fluoro~4-(2,2,2~trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyridofl ,2-a]pyrimidin-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H- pyrimido[l,2-a]pyriniidin-4-one: 3-(4-((2,2-difluorocyc1opropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyridofl, 2-a]pyrimidin-4-one; 3-(4-(2,2,2-trifluoroetiioxy)phenyl)-2-(triflaoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one: 3-(4~(2,2,2-trifluoroethoxy)phenyl)-2~(trifluoromethyl)-4H-pyrido[l,2-a.]pyrimidine~ 4,8(lH)-dione; 3-(4-(2,2-diflaoroethoxy)-2-fluorophenyl)-8-methoxy-2-(triflaoromethyl)-4H-pyridofl,2-a]pyrimidin-4-one: 3-(4-(2,2-difluoroethoxy)phenyi)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 3-(4-(2,2 -difluoropropoxy)phen yl)-8-me thoxy-2-(trifluorom ethyl) -4H-pyrido [ 1,2-a fpyrimidin-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimid!n-4-one; 3-(4-(cyclopropylmethoxy)phenyl)-8-metiioxy-2-(trifluoromethyl)-4H-pyrido| 1,2-a]pyrimidin-4-one; 4-oxo-3-(l -(2., 2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidme-8-carbonitrile; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyridofl,2-a]pyrimidine-8-carboxamide; 7-(1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-8-(trifluoromethyl)-2H-pyrimido[l,2-a]pyTimidine-2,6(lH)-dione; 7-chloro-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; -47. 7-chloro-8-methoxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl) -4H-[ 1,3] diazino [ 1,2-a]pyrimklin-4-one: 7-fluoro-8-methoxy-3-[l-(2,2,3,3,3-peutafltioropropyl)-lH-pyrazol-4-yl]-2- (trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-((lR)-l-hydroxyethyl)-3-(l-(2,2,3,3,3-pentaflaoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(( 1S)-1 -hydroxyethyl)-3-( 1 -(2,2,3,3,3-pentafluoropropyl)- lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one; 8-((dimethylammo)methyl)-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 8-(aminomethyl)-3-(l -(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(dimethylamino)-3-(l-(2,2,3,3,3-pentaflaoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 8-(fluoromethoxy)-3-[l-(2,2,3,3,3-pentafluoropropyl)-] H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(fluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-(hydroxymethyl)-3~(l -(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(hydroxyniethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifiuoromethyl)-4H- pyrido[ 1,2-a]pyrimidin-4~one: 8-(inethoxyinethyl)-3-[l~(2,2,3,3,3-pentafluoropropyl)-rH-pyrazol-4-yl]~2- (trifluoromethyl)-4H~pyrido[ 1,2-a]pyrimidin-4-one; 8-(methylamino)-3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidm-4-one; 8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l ,2-a]pyrimidm-4-one; 8-(methyloxy-d;,)-3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one; -48 - 8-(methyloxy-d3)-3-( 1-(2,2,3,3,3-pentafl uoropropy 1)-lH-pyrazol-4-y 1)-2-(trifluoromethyl)-4H-pyrimido[l,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyI)-4H- pyrimido[l,2-a]pynmidin-4~one: 8-amino-3-( 1-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(tri fluoromethyl)- 4H-pyrido [ 1,2-a] pyrim idin -4-one; 8-ammo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]py rimidin-4-one; 8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2~(trifluorometbyl)-4H-pyrirnido[l,2-alpyrimidm-4-one; 8-chIoro-3-(l -(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)- 4H-pyrido[ 1,2-a]pyrimidin-4-one: 8~ethoxy-3-(4~(2,2,2-trifluoroethoxy)phenyl)~2-(trifluorornethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-2 -(trifl uoromethyI)-3-(1 -(3,3,3 -trifluoropropyl)-1 H-py razol-4-yl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; 8-methoxy-3-(l -(2., 2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)- 4H-pyrido[ 1,2 -a] pyrimi din-4-one; 8-methoxy-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)- 4H-pyrimido[ 1,2-a]pyrimidin-4-one: 8~metboxy~3-(l-(4,4,4-trifluorobutyl)-lH~pyrazol-4~yl)-2~(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy')phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromefhyl)-4H-pyrimido[l,2-a]pyrimidin-4-one; .49. 8-inethoxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[l,2-a]pyrimidm-4-one; 8-methoxy-3-(6-(2.,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-metlioxy-3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-l,2,3-triazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one; 8~methoxy~3-[l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one; 8-methoxy-3-|2-(2,2,2-trifluoroethoxy)p\Timidin-5-yl]-2-(trifluoromethyl)-4H-pyrido [ 1,2-a]pyrimidin-4-one; or 8-methoxy-3-[2-(2,2,2~trifhioroethoxy)pyrimidm-5~yl]~2-(trifluoromethyl)-4H-pyrimi do [ 1,2-b]pyridazm -4-one. Provided herein as Embodiment 92 is the compound according to Embodiment 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is 4-oxo-3-(l-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4I-I-pyrido[l,2-a]pyrimidine-8-carbonitrile; 8-(methyloxy-d3)-3-( 1-(2,2,3,3,3-pentafl uoropropy 1)-lH-pyrazol-4-y 1)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluorometbyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8-methoxy-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 8~metboxy~3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrimido[l,2-a]pyrimidm-4-one; or 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido| 1,2-a]pyrimidm-4-one. - 50 - Provided herein as Embodiment 93 is the compound according to Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is Provided herein as Embodiment 94 is the compound according to Embodiment 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is F                          . Provided herein as Embodiment 95 is the compound according to Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is 10                               F                    , Provided herein as Embodiment 96 is the compound according to Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is -51 - Provided herein as Embodiment 97 is the compound according to Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is Provided herein as Embodiment 98 is the compound according to Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is F The foregoing merely summarizes certain aspects of this disclosure and is not intended, nor should it be construed, as limiting the disclosure in any way. FORMULATION AND ROUTE OF ADMINISTRATION 10           While it may be possible to administer a compound disclosed herein alone in the uses described, tire compound administered normally will be present as an active ingredient in a pharmaceutical composition. Thus, in one embodiment, provided herein is a pharmaceutical composition comprising a compound disclosed herein in combination with one or more pharmaceutically acceptable excipients, such as diluents, carriers, adjuvants and the like, and, 15 if desired, other active ingredients. See, e.g., Remington: The Science and Practice of Pharmacy, Volume I and Volume II, twenty-second edition, edited by Loyd V. Allen Jr., Philadelphia, PA, Pharmaceutical Press, 2012; Pharmaceutical Dosage Forms (Vol. 1-3), Liberman et al., Eds., Marcel Dekker, New York, NY, 1992; Handbook of Pharmaceutical Excipients (3rd Ed.), edited by Arthur H. Kibbe, American Pharmaceutical Association, 20 Washington, 2000; Pharmaceutical Formulation: The Science and Technology of Dosage Forms (Drag Discovery), first edition, edited by GD Tovey, Royal Society of Chemistry', - 02 - 2018. In one embodiment, a pharmaceutical composition comprises a therapeutically effective amount of a compound disclosed herein. The compound(s) disclosed herein may be administered by any suitable route in the form of a pharmaceutical composition adapted to such a route and in a dose effective for the treatment intended. The compounds and compositions presented herein may, for example, be administered orally, mucosally, topically, transdermally, rectally, pulmonarily, parentally, intranasally, intravascularly, intravenously, intraarterial, intraperitoneally, intrathecally, subcutaneously, sublingually, intramuscularly, intrastemally, vaginally or by infusion techniques, in dosage unit formulations containing conventional pharmaceutically acceptable excipients. The pharmaceutical composition may be in the form of, for example, a tablet, chewable tablet, minitablet, caplet, pill, bead, hard capsule, soft capsule, gelatin capsule, granule, powder, lozenge, patch, cream, gel, sachet, microneedle array, syrup, flavored syrup, juice, drop, injectable solution, emulsion, microemulsion, ointment, aerosol, aqueous suspension, or oily suspension. The pharmaceutical composition is typically made in the form of a dosage unit containing a particular amount of the active ingredient. Provided herein as Embodiment 99 is a pharmaceutical composition comprising the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable excipient. Provided herein as Embodiment 100 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use as a medicament. Further, this disclosure encompasses pharmaceutical compositions comprising mixtures of any of the compounds disclosed herein and one or more oilier active agents disclosed herein. METHODS OF USE As discussed herein (see, section entitled “Definitions”), the compounds described herein are to be understood to include all stereoisomers, tautomers, or pharmaceutically -53 - acceptable salts of any of the foregoing or solvates of any of the foregoing. Accordingly, the scope of the methods and uses provided in the instant disclosure is to be understood to encompass also methods and uses employing all such forms. Besides being useful for human treatment, the compounds provided herein may be useful for veterinary treatment of companion animals, exotic animals and farm animals, including mammals, rodents, and the like. For example, animals including horses, dogs, and cats may be treated with compounds provided herein . Provided herein as Embodiment 101 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in reducing the body weight. Provided herein as Embodiment. 102 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in reducing the body-mass-index of a subject. Provided herein as Embodiment 103 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in treating a metabolic disorder. Provided herein as Embodiment. 104 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in treating a cardiovascular disorder. Provided herein as Embodiment 105 is a compound according to any one of Embodiments 1 -98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in treating diabetes. Provided, herein as Embodiment. 106 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt, of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in treating obesity. -54- Provided herein as Embodiment 107 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in treating dyslipidemia. Provided herein as Embodiment 108 is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in treating non-alcoholic steatohepatitis (NASH). Provided herein as Embodiment 109 is a use of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 in the preparation of a medicament for reducing the body weight or the body-mass-index of a subject. Provided herein as Embodiment 110 is a use of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 in the preparation of a medicament for treating a metabolic or a cardiovascular disorder. Provided herein as Embodiment 111 is a use of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 in the preparation of a medicament for treating diabetes, obesity, dyslipidemia, or nonalcoholic steatohepatitis (NASH). Provided herein as Embodiment 112 is a method of reducing the body weight or the body-mass-index of a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Provided herein as Embodiment 113 is a method of treating a metabolic or cardiovascular disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to any one of - 55 - Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Provided herein as Embodiment 114 is a method of treating diabetes, obesity, dyslipidemia, or non-alcoholic steatohepatitis (NASH) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Provided herein as a further embodiment is a method of reducing the waist-to-hip ratio (WHR) of a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the compound according to any one of Embodiments 198, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Provided herein as a further embodiment is use of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 in the preparation of a medicament for reducing the waist-to-hip ratio (WHR) of a subject. Provided herein as a further embodiment is a compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99 for use in reducing the waist-to-hip ratio (WHR) of a subject. Provided herein as a further embodiment is a method of lowering blood glucose in a subject in need thereof, the method comprising administering a therapeutically effective amount of tire compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99, In some embodiments, the method lowers blood glucose 10% or greater. Tn some embodiments, the method lowers blood glucose 15% or greater. In some embodiments, the method lowers blood glucose 20% or greater. In some embodiments, the method lowers blood glucose 25% or greater. In some embodiments, the method lowers blood glucose while having minimal effect on food intake / appetite. In some embodiments, the method lowers blood glucose while having no effect on food intake / appetite. - 56 - Provided herein as a further embodiment is a method of lowering insulin in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1 -98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99. In some embodiments, the method lowers insulin 50% or greater. In some embodiments, the method lowers insulin 60% or greater. In some embodiments, the method lowers insulin 70% or greater. In some embodiments, the method lowers insulin 80% or greater. Tn some embodiments, the method lowers blood insulin 85% or greater. In some embodiments, the method lowers insulin 86% or greater. In some embodiments, the method lowers insulin 87% or greater. In some embodiments, the method lowers insulin 88% or greater. In some embodiments, the method lowers insulin 89% or greater. In some embodiments, the method lowers insulin 90% or greater. In some embodiments, the method lowers insulin 91% or greater. In some embodiments, the method lowers insulin while having minimal effect on food intake / appetite. In some embodiments, the method lowers insulin while having no effect on food intake / appetite. Provided herein as a further embodiment is a method of lowering cholesterol in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99. In some embodiments, the method lowers cholesterol 10% or greater. In some embodiments, the method lowers cholesterol 15% or greater. In some embodiments, the method lowers cholesterol 20% or greater. In some embodiments, the method lowers cholesterol 30% or greater. In some embodiments, the method lowers cholesterol 31% or greater. In some embodiments, the method lowers cholesterol 32% or greater. In some embodiments, the method lowers cholesterol 33% or greater. In some embodiments, the method lowers cholesterol 34% or greater. In some embodiments, the method lowers cholesterol 35% or greater. In some embodiments, the method lowers blood cholesterol 36% or greater. In some embodiments, the method lowers cholesterol 37% or greater. In some embodiments, the method lowers cholesterol 38% or greater. In some embodiments, the method lowers cholesterol 39% or greater. In some embodiments, the method lowers cholesterol while having minimal effect - - on food intake / appetite. In some embodiments, the method lowers cholesterol while having no effect on food intake / appetite. Provided herein as a further embodiment is a method of lowering LDL in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99. In some embodiments, the method lowers low-density lipoproteins (LDL) 10% or greater. In some embodiments, the method lowers LDL 20% or greater. In some embodiments, the method lowers LDL 21% or greater. In some embodiments, the method lowers LDL 22% or greater. In some embodiments, the method lowers LDL 23% or greater. In some embodiments, the method lowers LDL 24% or greater. In some embodiments, the method lowers LDL 25% or greater. In some embodiments, the method lowers LDL 26% or greater. In some embodiments, the method lowers blood LDL 27% or greater. In some embodiments, the method lowers LDL while having minimal effect on food intake / appetite. In some embodiments, the method lowers LDL while having no effect on food intake / appetite. Provided herein as a further embodiment is a method of low ering triglycerides in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99. In some embodiments, the method lowers triglycerides 30% or greater. In some embodiments, the method lowers triglycerides 40% or greater. In some embodiments, the method lowers triglycerides 50% or greater. In some embodiments, the method lowers triglycerides 51% or greater. In some embodiments, the method lowers triglycerides 52% or greater. In some embodiments, the method lowers triglycerides 53% or greater. In some embodiments, the method lowers triglycerides 54% or greater. In some embodiments, the method lowers triglycerides 55% or greater. In some embodiments, the method lowers blood triglycerides 56% or greater. In some embodiments, the method lowers triglycerides 57% or greater. In some embodiments, the method lowers triglycerides while having minimal effect on food intake / appetite. In -58- some embodiments, the method lowers triglycerides while having no effect on food intake / appetite Provided herein as a further embodiment is a method of lowering fat mass in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99, In some embodiments, the method lowers fat mass of a subject 30% or greater. In some embodiments, the method lowers fat mass of a subject 40% or greater. In some embodiments, the method lowers fat mass of a subject 45% or greater. In some embodiments, the method lowers fat mass of a subject 50% or greater. In some embodiments, the method lowers fat mass of a subject 55% or greater. In some embodiments, the method lowers blood fat mass of a subject 60% or greater. In some embodiments, the method lowers fat mass of a subject 65% or greater. In some embodiments, the method lowers fat mass of a subject 70% or greater. In some embodiments, the method lowers fat mass of a subject 75% or greater. In some embodiments, the method lowers fat mass of a subject while having minimal effect on food intake / appetite. In some embodiments, the method lowers fat mass of a subject while having no effect on food intake / appetite. Provided herein as a further embodiment is a method of raising adiponectin in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99, Provided herein as a further embodiment is a method of lowering leptin in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99, Provided herein as a. further embodiment, is a method of lowering resisten in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, ora -59- pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to embodiment 99. COMBINATIONS Provided herein is a further embodiment is a pharmaceutical composition comprising a compound according to any one of Embodiments 1-98 and one or more other active agents. In some embodiments, the one or more active agents include but are not limited to a source of omega-3 fatty acids. In some embodiments, the one or more active agents include but are not limited to omega-3 fatty acid supplements. In some embodiments, the one or more active agents include but are not limited to omega-3-carboxylic acids (e.g., Epanova®), omega-3 -acid ethyl esters (e.g., Lovaza® or Omtryg®) or icosapent ethyl (e.g., Vascepa®). Provided herein as a further embodiment is a method of treating diabetes, obesity, dyslipidemia, or non-alcoholic steatohepatitis (NASH) in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. In some embodiments, the one or more active agents include but are not limited to a source of omega-3 fatty acids. In some embodiments, the one or more active agents include but are not limited to omega-3 fatty acid supplements. In some embodiments, the one or more active agents include but are not limited to omega-3-carboxylic acids (e.g., Epanova®), omega-3-acid ethyl esters (e.g., Lovaza® or Omtryg®) or icosapent ethyl (e.g., Vascepa®). Provided herein as a further embodiment is a method of reducing body weight or the body-mass-index of a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. In some embodiments, the one or more active agents include but are not limited to a source of omega-3 fatty acids. In some embodiments, the one or more active agents include but are not limited to omega-3 fatty acid supplements, hi some embodiments, the one or more active agents - 60 - include but are not limited to omega-3-carboxylic acids (e.g., Epanova®), omega-3-acid ethyl esters (e.g., Lovaza® or Omtryg®) or icosapent ethyl (e.g., Vascepa®). Provided herein as a further embodiment is a method of treating a metabolic or cardiovascular disorder in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. In some embodiments, the one or more active agents include but are not limited. to a source of omega-3 fatty acids. In some embodiments, the one or more active agents include but are not limited to omega-3 fatty acid supplements, hi some embodiments, the one or more active agents include but are not limited to omega-3-carboxylic acids (e.g., Epanova®), omega-3-acid ethyl esters (e.g., Lovaza® or Omtryg®) or icosapent ethyl (e.g., Vascepa®). Provided herein as a further embodiment is a method of reducing the waist-to-hip ratio (WHR.) of a subject in need thereof, tire method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1 -98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of lowering blood glucose in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 198, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of lowering insulin in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of lowering cholesterol in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1- -61 - 98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer m combination with one or more other active agents. Provided herein as a further embodiment is a method of lowering LDL in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of lowering triglycerides in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 198, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of lowering fat mass in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1 -98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of raising adiponectin in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 198, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of lowering leptin in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. Provided herein as a further embodiment is a method of lo vermg resisten in a subject in need thereof, the method comprising administering a combination of a therapeutically effective amount of the compound according to any one of Embodiments 1-98, or a tautomer - 62 - thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in combination with one or more other active agents. In some embodiments, the one or more active agents of the combinations described herein or methods utilizing these combinations described herein include but are not limited to omega-3 -carboxylic acids (e.g., Epanova®), omega-3-acid ethyl esters (e.g., Lovaza® or Omtryg®) or icosapent ethyl (e.g., Vascepa®). DEFINITIONS Ilie following definitions are provided to assist in understanding the scope of this disclosure. Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the standard deviation found in their respective testing measurements. As used herein, if any variable occurs more than one time m a chemical formula, its definition on each occurrence is independent of its definition at every other occurrence. If the chemical structure and chemical name conflict, the chemical structure is determinative of the identity of the compound. Stereoisomers The compounds of the present disclosure may contain, for example, double bonds, one or more asymmetric carbon atoms, and bonds with a hindered rotation, and therefore, may exist as stereoisomers, such as double-bond isomers (i.e., geometric isomers (E / Z)), enantiomers, diastereomers, and atropoisomers. Accordingly, the scope of the instant disclosure is to be understood to encompass all possible stereoisomers of the illustrated compounds including the stereoisomerically pure form (for example, geometrically pure, enantiomerically pure, diastereomerically pure, and atropoisomerically pure) and stereoisomeric mixtures (for example, mixtures of geometric isomers, enantiomers, diastereomers, and atropoisomers, or mixtures of any of the foregoing) of any chemical -63 - structures disclosed herein (in whole or in part), unless the stereochemistry is specifically identified. If the stereochemistry' of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing all stereoisomers of it. If the stereochemistry of a structure or a portion of a structure is indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing only the stereoisomer indicated. A bond drawn with a wavy line indicates that both stereoisomers are encompassed. Uris is not to be confused with a wavy line drawn perpendicular to a bond which indicates the point of attachment of a group to the rest of the molecule. The term “stereoisomer” or “stereoisomerically pure” compound as used herein refers to one stereoisomer (for example, geometric isomer, enantiomer, diastereomer and atropoisomer) of a compound that is substantially free of other stereoisomers of that compound. For example, a stereoisomerically pure compound having one chiral center will be substantially free of the mirror image enantiomer of the compound and a stereoisomerically pure compound having two chiral centers will be substantially free of other enantiomers or diastereomers of the compound. A typical stereoisomerically pure compound comprises greater than about 80% by weight of one stereoisomer of the compound and equal or less than about 20% by weight of other stereoisomers of the compound, greater than about 90% by weight of one stereoisomer of the compound and equal or less than about 10% by weight of the other stereoisomers of the compound, greater than about 95% by weight of one stereoisomer of the compound and equal or less than about 5% by weight of the other stereoisomers of the compound, or greater than about 97% by weight of one stereoisomer of the compound and equal or less than about 3% by weight of the other stereoisomers of the compound. This disclosure also encompasses the pharmaceutical compositions comprising stereoisomerically pure forms and the use of stereoisomerically pure forms of any compounds disclosed herein. Further, this disclosure also encompasses pharmaceutical compositions comprising mixtures of stereoisomers of any compounds disclosed herein and the use of said pharmaceutical compositions or mixtures of stereoisomers. These stereoisomers or mixtures thereof may be synthesized in accordance with methods well -64- known in the art and methods disclosed herein. Mixtures of stereoisomers may be resolved using standard techniques, such as chiral columns or chiral resolving agents. See, for example, Jacques etal., Enantiomers, Racemates and Resolutions (Wiley-Interscience, New York, 1981); Wilen e / a / ., Tetrahedron 33:2725; Eliel, Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, Tables of Resolving Agents and Optical Resolutions, page 268 (Eliel, Ed., Univ, of Notre Dame Press, Notre Dame, IN, 1972). Tautomers As known by those skilled in the art, certain compounds disclosed herein may exist in one or more tautomeric forms. Because one chemical structure may only be used to represent one tautomeric form, it will be understood that for convenience, referral to a compound of a given structural formula includes other tautomers of said structural formula. For example, the following is illustrative of tautomers of the compounds of Formula I, wherein w, y and z are CRW, CRy, and CRZ, respectively, and x is COH: Rz O                  Rz O N ||     j—■*»...         m J Rw  H                  Rw Accordingly, the scope of the instant disclosure is to be understood to encompass all tautomeric forms of the compounds disclosed herein. Isotopicaliy-Labelled Compounds Further, the scope of the present disclosure includes all pharmaceutically acceptable isotopically-labelled compounds of the compounds disclosed herein, such as the compounds of Formula I, wherein one or more atoms are replaced by atoms having the same atomic number, but an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of isotopes suitable for inclusion in the compounds disclosed herein include isotopes of hydrogen, such as 2H and 3H, carbon, such as nC, 13C and WC, chlorine, such as 36CI, fluorine, such as !8F, iodine, such as ! M and 1 "I. nitrogen, such as ,3N and 1SN, oxygen, such as 15O, ’ '0 and !sO, phosphorus, such as 32P, and sulphur, such as 'S. Certain isotopically-labelled compounds of Formula I, for example, those -65 - incorporating a radioactive isotope, are useful in drug and / or substrate tissue distribution studies. Ilie radioactive isotopes tritium (3H) and carbon-14 (WC) are particularly useful for this purpose in view of their ease of incorporation and ready means of detection. Substitution with isotopes such as deuterium (2H or D) may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and hence may be advantageous in some circumstances. Substitution with positron emitting isotopes, such as nC, [SF, 15O and S3N, can be useful in Positron Emission Topography (PET) studies, for example, tor examining target occupancy. Isotopically-labelled compounds of the compounds disclosed herein can generally be prepared by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying General Synthetic Schemes and Examples using an appropriate isotopically-labelled reagent in place of the non-labelled reagent previously employed. Solvates As discussed above, the compounds disclosed herein and the stereoisomers, tautomers, and isotopically-labelled forms thereof or a pharmaceutically acceptable salt of any of the foregoing may exist in solvated or unsolvated forms. The term “solvate” as used herein refers to a molecular complex comprising a compound or a pharmaceutically acceptable salt thereof as described herein and a stoichiometric or non-stoichiometric amount of one or more pharmaceutically acceptable solvent molecules. If the solvent is water, the solvate is referred to as a “hydrate.” Accordingly, the scope of the instant disclosure is to be understood to encompass all solvents of the compounds disclosed herein and the stereoisomers, tautomers and isotopically-labelled forms thereof or a pharmaceutically acceptable salt of any of the foregoing. Miscellaneous Definitions llus section will define additional tenns used to describe the scope of the compounds, compositions and uses disclosed herein. -66- The terms “Cjjalkyl,” “CiYalkyl,” “TTealkyl,” and “Ci-ealkyl” as used herein refer to a straight or branched chain hydrocarbon containing from 1 to 3, 1 to 4, 2 to 6, and 1 to 6 carbon atoms, respectively. Representative examples of Cj.3alky1, Chalky!, Cz-salkyl, or Ci-ealkyl include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl and hexyl. The term “Cb-Aalkenyr as used herein refers to a saturated hydrocarbon containing 2 to 4 carbon atoms having at least one carbon-carbon double bond. Alkenyl groups include both straight and branched moieties. Representative examples of C2-4alkenyl include, but are not limited to, 1-propenyl, 2-propenyl, 2-methyl-2-propenyl, and butenyl. The terms “Ci-4alkylammo” or “Ci^alkylamino” as used herein refer to -NHR*, wherein R* represents a Cwalkyl and Ci-ealkyl, respectively, as defined herein. Representative examples of Cwalkylamino or Ct-salkylamino include, but are not limited to, -NfICH3, -NHCH2CH3, -NHCH2CH2CH3, and -NHCH(CH3)2. The term “C3-5cycloalkyl” as used herein refers to a saturated carbocyclic molecule wherein the cyclic framework has 3 to 6 carbons. Representative examples of C3-5cycloalkyl include, but are not limited to cyclopropyl and cyclobutyl. The term “deutero” as used herein as a prefix to another term for a chemical group refers to a modification of the chemical group, wherein one or more hydrogen atoms are substituted with deuterium (“D,” “d,” or “2H”). For example, the term “Cwdeuteroalkyi” refers to a Chalky! as defined herein, wherein one or more hydrogen atoms are substituted with D. Representative examples of Cwdeuteroalkyl include, but are not limited to, -CH2D, -CHD2, -CD3, -CH2CD3, -CDHCD3, -CD2CD3, -CH(CD3)2, -CD(CHD2)2, and -CH(CH2D)(CD3). The terms “diCwalkylaniino” or “'diCi-ealkylaroino” as used herein refer to -NR*R**, where in R* and R** independently represent a Ci-4alkyl and Ci-ealkyl, respectively, as defined herein. Representative examples of diCi^alkylamino or diCj.. salkylamino include, but are not limited to, -N(CH3)2, -N(CH2CH3)2, -N(CH3)(CH2CH3), -N(CH2CH2CH3)2, and -N(CH(CH3)2)2. The term “Ci-4alkoxy” or “Ci-3alkoxy” as used herein refers to -OR#, wherein R# represents a Chalky! group or Cwalkyl group, respectively, as defined herein. -67- Representative examples of Cwalkoxy or Ci jalkoxy include, but are not limited to, methoxy, ethoxy, propoxy, iso-propoxy, and butoxy . The term “halogen” as used herein refers to -F, -CI, -Br, or -I. The term “halo” as used herein as a prefix to another term for a chemical group refers to a modification of the chemical group, wherein one or more hydrogen atoms are substituted with a halogen as defined herein. The halogen is independently selected at each occurrence. For example, the term “Cwhaloalkyl” refers to a Chalky! as defined herein, wherein one or more hydrogen atoms are substituted with a halogen. Representative examples of Cj. 4haloalkyl include, but are not limited to, -CH2F, -CHF2, -CF3,-CHFC1, -CH2CF3, -CFHCF3, -(T TT;. -CH(CF3)2, -CFiCHF j3. and -CH(CH2F)(CF3). The term “5-membered heteroaryl” as used herein refers to a 5-membered carbon ring with two double bonds containing one ring heteroatom selected from N, S, and O and optionally one or two further ring M atoms instead of the one or more ring carbon atom(s). Representative examples of a 5-membered heteroaryl include, but are not limited to, furyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, and oxazolyl. The term “Cr-sheterocycloalkyl” or “Cj^heterocycloalky!” as used herein refers to a saturated carbocyclic molecule wherein the cyclic framework has 3 to 5 carbons or 3 to 4 carbons and wherein one carbon atom is substituted with a heteroatom selected from N, O, and S. Representative examples of Cs-sheterocycloalkyi or Cvjheterocycloalkyl include, but are not limited to aziridnyl, azetidinyl, oxetanyl, and pyrrolidinyl. The term “pharmaceutically acceptable” as used herein refers to generally recognized for use in subjects, particularly in humans. Ilie term “pharmaceutically acceptable salt” as used herein refers to a salt of a compound that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, and the like; or (2) salts formed when an acidic proton present in the -68- parent compound either is replaced by a metal ion, for example, an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, dicyclohexylamine, and the like. Additional examples of such salts can be found in Berge ei al, J. Pharm. Sci. 66(1):1-19 (1977). See also Stahl etal., Pharmaceutical Salts: Properties, Selection, and Use, 2nd Revised Edition (2011). The term “pharmaceutically acceptable excipient.” as used herein refers to a broad range of ingredients that may be combined with a compound or salt disclosed herein to prepare a pharmaceutical composition or formulation. Typically, excipients include, but are not limited to, diluents, colorants, vehicles, anti-adherants, glidants, disintegrants, flavoring agents, coatings, binders, sweeteners, lubricants, sorbents, preservatives, and the like. The term “subject” as used herein refers to humans and mammals, including, but not limited to, primates, cows, sheep, goats, horses, dogs, cats, rabbits, rats, and mice. In one embodiment the subject is a human. The term “therapeutically effective amount” as used herein refers to that amount, of a compound disclosed herein that will elicit the biological or medical response of a tissue, a system, or subject that is being sought by a researcher, veterinarian, medical doctor or other clinician. The term “body-mass-index” (“BMI”) as used herein may be calculated, for example, by determining a subject’s weight in kilograms and dividing it by the square of height in meters. See, e.g., https: / / www.cdc.gov^ealthyweight / assessing^mi / index.html (last accessed November 4, 2019). The BMI is an indicator of the amount of body fat in a subject, such as a human. The BMI is used as a screening tool to identify whether a subject is at a healthy weight or responds to weight loss treatment, SYNTHETIC PROCEDURES The compounds provided herein can be synthesized according to the procedures described in this and the following sections. The synthetic methods described herein are merely exemplary, and the compounds disclosed herein may also be synthesized by alternate routes utilizing alternative synthetic strategies, as appreciated by persons of ordinary skill in the art. It should be appreciated that the general synthetic procedures and specific examples -69- provided herein are illustrative only and should not be construed as limiting the scope of the present disclosure in any manner. All starting materials are either commercially available, for example, from Sigma-Aldrich Chemical Company, Inc., St. Louis, MO, USA, or known in the art and may be synthesized by employing known procedures using ordinary skill. Starting material may also be synthesized via the procedures disclosed herein. As can be appreciated by the skilled artisan, the representative examples are not intended to comprise a comprehensive list of all means by which the compounds described and claimed in this application may be synthesized. Further methods will be evident to those of ordinary skill in the art. Additionally, the various synthetic steps described above may be performed in an alternate sequence or order to give the desired compounds. Purification methods for the compounds described herein are known in the art and include, for example, crystallization, chromatography (for example, liquid and gas phase), extraction, distillation, trituration, and reverse phase HPLC. The disclosure further encompasses “intermediate” compounds, including structures produced from the synthetic procedures described, whether isolated or generated in-situ and not isolated, prior to obtaining the finally desired compound. These intermediates are included in the scope of this disclosure. Exemplary embodiments of such intermediate compounds are set forth below. Provided herein as Embodiment 115 is a compound, wherein the compound is N-(3“iodo-4-oxo-2-(tritluoromethyl)-4H-pyrido[l,2-a]pyrimidin-8-yl)acetamide; 8-bromo-3-iodo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin -4-one; 8~bromo~2.-(trifluoromethyl)-4H-pyrido[l ,2-a]pyrimidin~4-one; 8-hydroxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one; 4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carbonitrile; 3-Iodo-4-oxo-2-(trifluoromethyl)-4H-pyridojT,2-a]pyrimidine-8-carbonitrile; 3-bromo-8-methoxy-2-(trifluoromethyl)pyrimido[l,2-a]pyrimidm-4-one; 8-methoxy-2-(trifluoromethyl)-4H-pyrimido[l,2-a.]pyrimidin-4-one; or l-(2,2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole. - 70 - EXAMPLES This section provides specific examples of compounds of Formula I and methods of making the same. List of Abbreviations 5 Table 1 AcOH acetic acid A IBM Azobisisobutyronitrile aq or aq. aqueous BOC or Boc tert-butyloxycarbonyl Cu(OTf)2 C opper trifluoromethanesulfonate Cy Cyclohexane DAST Diethylaminosulfur trifluoride DCE 1,2-dichloroethane DABCO l,4-diazabicyclo[2.2.2]octane DIBAL-U Dii sobutylaluminum hydride DCM di chloromethane DIAD Diisopropyl azodiformate DMA A / A-dimethylacetamide DMAP 4-dimethylaminopyridine DME 1,2. -dimethoxyethane DMF N ,N -dimethylformamide DMSO dimethyl sulfoxide DMP Dess-Martin Periodinane Dppf, DPPF or dppf 1,1’ -bis(diphenylphosphino)ferrocene eq or eq. or equiv. equivalent ESI or ES electrospray ionization Et ethyl id-0 diethyl ether EtOAc ethyl acetate -71 - g gram(s) h hourfs) HATU (1 -[Bis(dimethylamino)methylene] -1H-1,2,3 - tnazolo[4,5-b]pyridinrum 3-oxide hexafluorophosphate HBTU N,N,N',NMetramethyl-O-(lH-benzotriazol-l-yl)uronium hexafluorophosphate, O-(benzotriazol~ 1 -yl)-N,N ,N’,N'-tetramethyiuronium hexafluorophosphate HPLC high pressure liquid chromatography iPr isopropyl iPr2NEt or DIPEA N-ethyl diisopropylamine (Hiinig’s base) KHMDS potassium hexamethyldisilazide KOAc potassium acetate LC MS, LCMS, LC-MS or LC / MS liquid chromatography mass spectroscopy LG leaving group (e.g., halogen, mesylate, triflate) LHMDS or LiHMDS lithium hexamethyldisilazide m / z mass divided by charge mCPBA meVa-chloroperoxybenzoic acid Me methyl MeCN acetonitrile MeOH methanol Met metal species for cross-coupling (e.g., MgX, ZnX, SnR3, SiR3, B(OR)2) pm micrometer pL or pl microliter mg milligrams min minutes ml. or ml milliliters MS mass spectra NaHMDS sodium hexamethyldisilazide -72- NBS N-bromosuccinimide n~BuLi n-butyllithium NTS N-iodosuccinimide NBS N-bromosuccinimide NCS N -ch] orosu ccini mi d e NMP A-Methy 1-2-pyrrolidone NMR nuclear magnetic resonance Pd-118, Pd(dtbpf)Cl2 1,1 '-bis(di -rm-butylphosphino)ferrocene] -di chi oropalladium(II) dichloride Pd 2(dba)3 tris(dibenzylideneacetone)dipalladium(0) Pd(dppf)C12 [1,1 '~bis(dipheny lphosphino)ferrocene] -di chi oropalladium(ri) Pd(dppf)Cl2DCM [1,1 '-bis(dipheny lphosphino)ferrocene] -dichloropalladium(Tl), complex with dichloromethane Pd(PPh3)4 tetrakis(triphenvlphosphine)palladium(0) Ph phenyl PPA Polyphosphoric acid PR or PG or Prot. group protecting group rbf round-bottomed flask RP HPLC reverse phase high pressure liquid chromatography RT or rt or r.t. room temperature sat. or satd. saturated sex Strong Cation Exchange SFC supercritical fluid chromatography SIPr l,3-Bis(2,6-diisopropylphenyl)imidazolidene SPhos 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl SPhos Palladacycle or SPhos Palladacycle G1 (2-DicyclohexyIphosphino-2',6'-dimethoxy-1,1 '-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) chloride methyl-t-butylether adduct -73 - Sphos Palladacycle G3 (2-dicyclohexylphosphino~2 / ,6''-dimethoxybiphenyl) [2 (2 '-amino-1,1 '-biphenyl) ]palladium(II) methanesulfonate TBAF tetra-n-butylammonium fluoride TBTU N,N,N',N'-tetramethyl-O-(benzotriazol-l-yl)uronium tetrafluoroborate tBuBrettPhos Palladcycle G3 Methanesulfonato(2-(di~t-butylphosphino)~3,6-dimethoxy-2',4',6'-tri-i -propyl-1,1 '-biphenyl)(2‘-amino-1,1' -biph eny I -2 -yl )pal ladium (II) t-BuOH tert-butanol TEA or Et3N trimethylamine TFA trifluoroacetic acid THF tetrahyd roforan UV ultraviolet XantPhos 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene General Analytical and Purification Methods Provided in this section are descriptions of the general analytical and purification methods used to prepare the specific compounds provided herein. Chromatography: 5            Unless otherwise indicated, crude product-containing residues were purified by passing the crude material or concentrate through either a Biotage or Isco brand silica gel column (pre-packed or individually packed with SiO?) or reverse phase flash silica (Cl8) and eluting the product off the column with a solvent gradient as indicated. For example, a description of (330 g SiO?, 0-40% EtOAc / hexane) means the product was obtained by elution 10 from the column packed with 330 grams of silica, with a solvent gradient of 0% to 40% EtOAc in hexanes. Preparative HPLC Method: Where so indicated, the compounds described herein were purified via reverse phase HPLC using one of tire following instruments: Shimadzu, Varian, Gilson, Agilent 1260 15 infinity-7 or Waters Fractionlynx; utilizing one of the following HPLC columns: (a) a. -74- Phenomenex Luna or (b) a Gemini column (5 micron or 10 micron. C18, 150x50 mm) or (c) a Waters X-select CSH column (5 micron, C18, 100x30 mm), unless otherwise indicated. A typical am through the instalment included: eluting at 45 mL / min with a linear gradient of 10% (v / v) to 100% MeCN (0.1% v / v TFA) in water (0.1% TFA) over 10 minutes; conditions can be varied to achieve optimal separations. Proton NMR Spectra: Unless otherwise indicated, all 5H NMR spectra were collected on a Bruker NMR Instrument at 300 MHz or 400 or 500 MHz. Where so characterized, all observed protons are reported as parts-per-million (ppm) downfield from tetramethylsilane (TMS) or other internal reference in the appropriate solvent indicated. Mass Spectra (MS) Unless otherwise indicated, all mass spectral data for starting materials, intermediates and / or exemplary compounds are reported as mass / charge (m / z), having an [M-t-Hty molecular ion. The molecular ion reported was obtained by electrospray detection method (commonly referred to as an ESI MS) utilizing a PE SCIEX API 150EX MS instrument, an Agilent 1100 series LC / MSD system or a Waters Acquity UPLC / MS. Compounds having an isotopic atom, such as bromine and the like, are generally reported according to the detected isotopic pattern, as appreciated by those skilled in the art. Compound Names The compounds disclosed and described herein have been named using the IUPAC naming convention provided with Chem-Draw Professional 15.1.0.144 software, ACD / Labs software version 2015 from Advanced Chemistry Development Inc., or with JChem for Excel 18.22.1.7 from ChemAxon Ltd. Specific. Examples Provided in this section are the procedures to synthesize specific examples of the compounds provided herein. All starting materials are either commercially available from Sigma-Aldrich Chemical Company, Inc., St. Louis, MO, USA, unless otherwise noted, or -75 - known in the art and may be synthesized by employing known procedures using ordinary skill. Synthesis of Intermediates: Intermediate 1-A 3-Bromo-8-methoxy-2-(trjfhioromethyI)-4H-pyrjdo[l,2~a]pyrimidjn-4~one Br2, AcOH O Step 2 Step 1: 8-Methoxy-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one. A reaction mixture of 2-amino-4-methoxypyridine (3.91 g, 31.5 mmol, Oakwood Products, Inc.), ethyl 4,4,4-trifluoroacetoacetate (18.56 ml, 126 mmol), and bismuth(III) trichloride (1.091 ml, 15.75 mmol) was heated to 100°C for 5h. The reaction mixture was cooled to rt, diluted with water and extracted with EtOAc. The organic layer was washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (eluent: 0-60% EtOAc / heptane) to afford 8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one (2.16 g, 8.9 mmol, 28%yield). LC / MS (ESP) m / z = 245.2 [M+HJ2 Step 2: 3-Bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. A solution of bromine (8 pl, 0.16 mmol) in acetic acid (0.5 ml) was added dropwise to a solution of 8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (40 mg, 0.16 mmol) in acetic acid (1.2 ml) at rt. Upon completed addition, the reaction mixture was cooled to 0°C and diluted with EtOAc (5 mL) and water (2 mL). The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure. The crude -76- materiai was purified silica gel chromatography (eluent: 5-50% EtOAc / heptane) to afford 3-bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (52 mg g, 0.16 mmol. 98% yield) as a white solid. MS (ESF) m / z = 323.0 [M+HJ*. ’H NMR. (400 MHz. CDCfi) 5 8.97 (d, 1=7.82 Hz, 1H) 7.05 (d, 1=2.74 Hz, 1H) 6.98 (dd, 1=7.92, 2.64 Hz, 1H) 4.02 (s, 3 H). Intermediate 1-B 3-Iodo-8-methoxy-2-(trifluoromethyI)-4H-pyrido[l,2-ajpyrimidin-4-one Step 1                                   Step 2 Step 1: 8-Methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-A, Step 1. Step 2: 3-Iodo~8-methoxy-2-(trifiuoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one. To a solution of 8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.22 g, 0.89 mmol) in acetonitrile (5 mL) was added N-iodosuccinimide (0.24 g, 1.1 mmol). Ilie reaction mixture was heated to 80°C for 12 h. The reaction mixture was concentrated in vacuo and the crude residue was purified by silica gel chromatography (eluent: 100% DCM) to give 3-iodo-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.31 g, 0.84 mmol, 94% yield). LC / MS (ESH) m / z = 370.9 | M • I H . 371.9 M 2H | . TI NMR. (400 MHz, CDCI3) 8 8.98 (d, J 7.82 Hz, 1H), 7.06 (d, 1 2.74 Hz, 1H), 6.97 (dd, 1=2.64, 7.92 Hz, 1H), 4.02 (s, 3H). 19F NMR (376 MHz, CDCb) 5 -67.21 (s, 3F). -77- Intermediate 1-C 3-Bromo-2-(difluoromethyl)-8-methoxy-pyrido[l,2-a]pyrimidin-4-one Step 1: 2-(DifIuoromethyI)-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one. A solution of 4~methoxypyridin-2-amine (3.75 g, 30.2 mmol, Combi-Blocks Inc.) and 4,4-difluoro-3-oxobutanoic acid ethyl ester (7.5 ml, 45 mmol, Combi-Blocks Inc.) in glacial acetic acid (25 ml, 433 mmol) was heated to reflux for 18 h. The reaction mixture was concentrated under reduced pressure and then partitioned between CH2Q2 (50 mL) and 5 M NaOH (20 mL). The organic layer was extracted with CH2Q2 (2.x) and the combined organic layers were dried overNa2SO4. Tire filtrate was concentrated in vacuo. Tire crude residue was suspended in DCM (10 mL) and filtered. The filtrate was purified by silica gel chromatography (eluent: 0-35% (3:1 EtOAc / EtOH) / heptane) to afford 2-(difluoromethyl)-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one (0.92 g, 4.1 mmol, 14% yield) as a solid. !H NMR (400 MHz, CDCh) 8 8.95 (d, 1=7.9 Hz, 1H), 6.97 (d, 1=2.5 Hz, 1H), 6.88 (dd, 1=7.9, 2.70 Hz, 1H), 6.54 (s, 1H), 6.43 (m, IH), 3.99 (s, 3H). Step 2: 3~Bromo-2-(difhwromethyI)-8-methoxy-pyrido[l,2-a]pyrimidin-4-one. l,3-Dibromo-5,5-dimethylhydantom (0.81 g, 2.9 mmol) was added to a stirring suspension of 2-(difluoromethyl)-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one (0.92 g, 4.1 mmol) in DMF(7 mL) / DCM (4 mL) at -45 °C under nitrogen atmosphere. After 30 min, the reaction was treated with saturated aqueous NaHCOa solution (20 ml.,) and EtOAc (25 mL) -78- and after stirring for 15 min, the resulting precipitate was filtered off. The organic phase of the filtrate was separated, washed with brine (10 mL), and dried over NazSOi. The filtrate was concentrated under reduced pressure. The crude material was suspended in DCM (5 ml). The solid as filtered off and dried to obtain 3-bromo-2-(difluoromethyl)-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one (0.73 g, 2.4 mmol, 59% yield) as a white solid. LC / MS (EST) m / z == 305.0 | M • H i . H NMR (400 MHz, CDC13) 8 8.96 (d, 1==7.88 Hz, 1H), 7 077 08 (m, 1H), 6.93 (t, 1=52 Hz, 1H), 6.95 (d, J 2 7 Hz, 1H), 4.00 (s, 3H1 Intermediate 1-D Methyl 3-iodo-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxylate Step 1: Methyl 4~oxo-2-(trifluoromethyI)-4H~pyrido[l,2-a]pyrimidine~8-£arboxyIate. A pressure autoclave was charged with 8-bromo-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one (10 g, 34 mmol, Intermediate 3-C), methanol (10 mL), DIPEA (30 mL, 171 mmol) and Pd(dppf)C12 (2.5 g, 3.1 mmol). The reaction mixture was heated to 70°C for 20h under an atmosphere of carbon monoxide (70 psi pressure). The reaction mixture was cooled to rt and filtered through a pad of celite. Tire celite pad was washed with dichloromethane (3x50 mL). The combined filtrate was concentrated under reduced pressure. Hie residue was taken up with water (100 mL) and extracted with DCM (3 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over NazSO^ filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (eluent: 15% ethyl acetate / hexane) to afford methyl 4-oxo-2-(trifluoromethyl)-4H~pyndo[ l,2-a]pyrimidine-8-carboxylate (6.7 g, 72% yield) as a pale yellow solid. LC / MS (ESI ) m / z == 273.1 | M • Hi . !H NMR (400 MHz, DMSO-de) 6 9.07 (d, .79. J 7.4 Hz, 1H), 8.20 (d, J 1.9 Hz, 1H), 7.73 (dd, J 7.2. 1.8 Hz, 1H), 7.00 (s, 1H), 3.96 (s, 3H). Step 2: Methyl 3-iodo-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxylate. The titie compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Step 2 was performed with methyl 4-oxo-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidine-8-carboxylate. LC / MS (ESI+) m / z :=== 398.9 . Intermediate 1-E 8-(Dimethy! amino)-3-iodo-2-(trifluoromethy!)-4H-pyrido[l,2-a] pyrimidin-4-one intermediate 3-1 Step 1: 8-(DimethyI ammo)-34odo-2-(trifluoromethy!)-4H-pyrido[l,2-a] pyrimidineone. A resealable vial was charged with 8-bromo-3-iodo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.5 g, 1.2 mmol, Intermediate 3-1), DMF (5 mL), copper(I) iodide (52 mg, 0.28 mmol) and dimethyl amine (0.66 mL, 1.3 mmol) under nitrogen atmosphere. Ilie reaction mixture was stirred at 80°C for 3h. The reaction mixture was cooled to rt, diluted with water and extracted with ethyl acetate (2 x 30 mL). The combined organic layers were washed with ice cold water (3 x 20 mL), dried over NazSCU and concentrated under reduced pressure. Tire crude residue was purified by silica gel chromatography (eluent: 25-30% ethyl acetate / hexane) to provide 8-(dimethyl amino)-3-iodo-2-(trifluoromethyl)-4H-pyrido[l,2-a] pyrimidin-4-one (0.32 g, 0.84 mmol, 70% yield) as a solid. LC / MS (ESH) m / z == 384.1 [M +H]1HNMR(400 MHz, DMSO-d6) 8 8.74 (d, 1=8.1 Hz, 1H), 7.20 (dd, J 8.2. 2.9 Hz, 1H), 6.66 (d, 1 2.9 Hz, 1H), 3.19 (s, 6H). - 80 - Intermediate 1-F 3-Iodo-8~(methyiamino)-2-(trifluoromethyl)-4H-pyridon,2-a] pyrimidin-4-one intermediate 34 Step 1: 3-Iodo-8-(methylamino)-2-(trifluoromethyI)-4H-pyrido[l,2-a] pyrimidin-4-one. Ilie title compound was prepared using the procedure described for Intermediate 1-E, Step 1 with the following modification: Step 1 was performed with methylamine. LC / MS (ESH) m / z = 370.2 [M+H]+. 5HNMR (400 MHz, DMSO-d6) 5 8.67 (d, 1=7.8 Hz, IH), 8.04 (d, 1=6.5 Hz, IH), 6.96 - 6.84 (m, IH), 6.48 (s, IH), 2.87 (d, J 4.8 Hz, 3H). Intermediate 1-G 8-AcetyI-3-iodo-2-(trifluoromethyS)-4H-pyrido[l,2-a]pyrimidin-4-one O Intermediate 3-1 (1) TnbutyHI-efhoxyvinyOtm, Step 1: 8-Acetyl-3-iodo-2-(trifliioroniethy!)-4H-pyrido[l,2-a]pyriniidin-4-one. A pressure tube was charged with 8-bromo-3-iodo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (2.5 g, 6.0 mmol, Intermediate 34), toluene (25 ml) and tributyl(l~ethoxyvinyl)stannane (2.2 g, 6.0 mmol). The reaction mixture was purged with nitrogen for 10 minutes, followed by the addition of Pd(PPhs)4 (0.69 g, 0.6 mmol). The reaction mixture was heated to 105°C for Ih. The reaction mixture was cooled to rt and filtered through a pad of celite. The filtrate was concentrated under reduced pressure to get a crude residue, which was dissolved in acetone (35 mL). The solution was cooled to 0°C and treated with 10% aqueous HC1 solution (17 ml). The reaction mixture was warmed to rt and - 81 - stirred for 30 min. The volatiles were removed under reduced pressure and the remaining residue was diluted with water (20 mL) and extracted with dichloromethane (3x30 mL). The combined organic layers were dried over NajSO* and the filtrate was adsorbed onto a plug of silica gel. Purification by silica gel chromatography (eluent: 0-20% EtOAc / hexane) afforded 8-acetyl-3-iodo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (700 mg, 31% yield) as yellow solid. LC / MS (EST) m / z- 382.9 | M ■ H L TINMR (400 MHz, DMSO-d6) 5 9.02 id, J 7.5 Hz, 1H), 8.43 (d, 11» Hz, 1H), 7.72 (dd, J %. 2.0 Hz, 1H), 2.74 (s, 3H). Intermediate 1-H 3~Iodo~4~oxo-2-(trifl!wromethyI)-4H~pyrido[l,2~a]pyrimidme-8-£arb(mitriIe Zn(CN)2 Pd(PPh3)4 NMP “ Step 1 Step 1: 4-Oxo-2-(trifluoromethy!)-4H-pyrido[l,2-a]pyrimidine-8-carbonitri!e. A resealable vial was charged with 8-bromo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.3 g, 1.0 mmol, Intermediate 3-C), zinc cyanide (0.12 g, 1.0 mmol), and Pd(PPh3)4 (0.12 g, 0.10 mmol). The vial was evacuated and backfilled with nitrogen. This procedure was repeated 3 times, followed by the addition of NMP (5 ml). Tire reaction mixture was heated to 90°C. After 18 h, the reaction mixture w as partitioned between EtOAc and water. The organic phase was washed with brine, dried over MgSO4, filtered, and adsorbed onto a plug of silica, gel. Purification by silica gel chromatography (eluent: 0-10% (3:1 EtOAc / EtOH) / heptane) provided 4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carbonitrile (0.16 g, 0.66 mmol, 64% yield) as a yellow' solid. LC / MS (ESH) m / z ::: 240.0 [M HiH NMR (CDCL, 400 MHz) 8 9.10 (d, J 7.5 Hz, 1H), 8.10 (s, 1H), 7.28-7.33 (m, 1H), 6.93 (s, 1H). Step 2: 3-Iodo-4-oxo-2-(trifluoromethyi)-4H-pyrido[l,2-ajpyrimidine-8-carbonitriie. The title compound was prepared using the procedure described for Intermediate 1 B, Step 2 with the following modification: Step 2 was performed with 4-oxo-2- - 82 - (Mfluoromethyl)-4H-pyridojT,2-a]pyrmudine-8-carbonitrile. LC / MS (LSI ) m / z=== 366.0 IM Hi \ !HNMR(400 MHz, CDC13) 5 9.02 (d, 1==7.4 Hz, 1H), 8.61 (d, J i .8 Hz, 1H), 7.73 (dd, J 7.4. 1.9 Hz, 1H). Intermediate l-I 7-ChIoro-3-iodo-8-methoxy-2-(trifIuoromethyl)-4H-pyrido[l,2-aJpyrimidin-4-one T! Step 1: 7-Chioro-8-methoxy-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-A, Step 1 with the following modification: Step 1 was performed with 5-chloro-4- 10   methoxypy ri din-2-amine (prepared according to the procedure described in WO2017 / 200825A1). LC / MS (ESL) m / z = 279.0 [M+H] \ 'HNMR (400 MHz, DMSO-d6) 8 9.04 (1H, s) 7.47 (1H, s) 6.70 (1H, s) 4.13 (4 H, s). Step 2: 7~Chloro~3-iodo~8~methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. 15           Tire title compound was prepared using the procedure described for Intermediate 1 B, Step 2 with the following modification: Step 2 was performed with 7-chloro-8-methoxy-2-(trifluoroniethyl)-4H~pyrido[l,2-a]pyrimidm-4-one. LC / MS (ESI4) m / z ==405.0 Hi . lH NMR (400 MHz, UMSO-dj 8 9.03 (1H, s) 7.45 (HL s) 4.13 (3H, s). Intermediate 1-J 20 2-(Difluoromethy!)-3-iodo-4-oxo-4H-pyrido[l,2-a]pyrimidine-8-carbonitriIe Step 1: 2-(DifluoromethyI)-4-oxo-4H-pyrido[l,2-a]pyrimidine-8-carboiiitriie. The title compound was prepared using the procedure described for Intermediate 1-A, Step 1 with the following modification: Step 1 was performed with 2-ammoisonicotinonitrile and 4,4-difluoro-3-oxobutanoic acid ethyl ester (Combi-Blocks Inc). LC / MS (ESL) m / z 222 J [M+Hf. 5H NMR (400 MHz, DMSO-d6) 8 6.77 - 7.09 (t, 1H) 6.82 (s, 1H) 7.59 - 7.67 (d, 1H) 8.53 (s, 1H) 8.97 - 9.07 (d, 1H). Step 2: 2~(DifluoromethyI)-3-iodo-4-oxo-4H-pyrido[l,2~ajpyrimidine-8-carbonitrile. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Step 2 was performed with 2-(difluoromethyl)-4-oxo-4H-pyrido[l,2-a]pyriniidine~8-carbonitrile. LC / MS (ESL) m / z ==348.1 [M+Hj+. NMR (400 MHz, DMSO-de) 8 6.96 - 7.29 (t, 1H) 7.67 (dd, 1H) 8.58 (d, 1H) 9.00 (dd, 1H). Intermediate 1-K 3-Iodo-8-(methylthio)-2-(trifluoromethyI)-4H~pyrido[l,2-a]pyrimidin-4~one Step 1: 4-(Methylthio)pyridin-2-amine. Sodium thiomethoxide (65.4 g, 933 mmol, Chempure) was added to a solution of 4-chloropyridm~2-amine (20 g, 156 mmol, Combi-Blocks, Inc.) in water (300 mL) at it. Ilie reaction mixture was stirred at 100°C for 2d, The reaction was quenched with water (300 mL) and extracted with EtOAc (2 x 250 mL). The combined organic layers were washed with brine (250 mL), dried over NaiSCL filtered and concentrated under reduced pressure to afford 4-(methylthio)pyridin-2-amine (18.0 g, 83% yield) as a yellow' solid. The product was -84- used in next step without further purification. LC / MS (ESH) rn / z :::: 141.1 [M+H]+. NMR (400 MHz, DMSO-dJ 5 7.72 (d, J 5.5 Hz, IH), 6.36 (dd, J 5.5. 1.7 Hz, IH), 6.27 (d, J L7 Hz, IH), 5.89 (s, 2H), 2.41 (s, 3H). Step 2: 8-(Methylthio)-2-(tnflnoromethyI)-4H-pyrido[l,2-a|pyrimidm-4-one. Ilie title compound was prepared using the procedure described for Intermediate 1-A, Step 1 with the following modification: Step 1 was performed with 4-(methyltbio)pyridin-2-amine. LC / MS (ESI*) m / z = 261.1 [M+H]4. ‘HNMR (400 MHz, DMSO-d6) 6 8.80 (dd, 1=7.6, 1.4 Hz, IH), 7.49 (d, 1=2.1 Hz, IH), 7.39 (dt, 1=7.6, 1.8 Hz, IH), 6.70 (d, 1=1.4 Hz, IH), 2.69 (d, 1=1.6 Hz, 3H). Step 3: 3-Iodo-8-(methyIthio)~2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 12. with the following modification: Step 2 was performed with 8-(methylthio)-2-(trifluoromethyl)-4H~pyrido[l,2~a]pyrimidin-4-one. LC / MS (ESI4) m / z = 386.9 [M+H]*. !H NMR (400 MHz, DMSO-d6) 8 8.79 (d, 1=7.5 Hz, IH), 7.48 - 7.40 (m, 2H), 2.69 (s, 3H). Intermediate 1-L N-(3-Iodo-4-oxo-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-8-yl)acetamide H3CC(O)NH2 Pd2(dba)3, Xantphos - Cs2CQ5, dioxane Step 1 O Step 1: N-(3-Iodo-4-oxo-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-8-yi)acetamide. A resealable vial was charged with 8-bromo-3-iodo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.1 g, 0.239 mmol, Intermediate 3-1), acetamide (19 mg, 0.32 mmol), cesium carbonate (0.16 g, 0.48 mmol), and dioxane (1 mL). The reaction mixture was purged with nitrogen for 10 minutes, followed by addition of Pdz(dba)3 (11 mg, 0.012 mmol) and Xantphos (7 mg, 0.012 mmol). The reaction mixture was then heated to 80°C for 5 h. Ure reaction mixture was cooled to room temperature and concentrated under reduced - 85 - pressure. The crude residue was purified by silica gel chromatography (eluent: 50-70% ethyl acetate / hexane) to afford N-(3-iodo-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-8-yl)acetamide (0.035 g, 0.088 mmol, 37%) as yellow solid. LC / MS (ESI+) m / z = 397.9 [M+H]’. Intermediate 1-M 3-Iodo-8-isopropyI-2-(trifiuoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one O Intermediate 3-C Step 1 CoCI2, LPrMgCI, benzene, THF O Step 1: 8-IsopropyL2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. Isopropyl magnesium chloride (2M in THF, 4,3 mL, 8.5 mmol,) was added drop wise to a solution of 8-bromo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrnmdin-4-one (1.0 g, 3.4 mmol, Intermediate 3-C) and CoCh (0.22 g, 1.7 mmol) in benzene (10 mL) at it under nitrogen atmosphere. Ilie reaction mixture was stirred at 80°C for 3h. The reaction mixture was diluted with aq. 1.5 N HCl (5 mL) and extracted with ethyl acetate (2. x 25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. Ilie crude material was purified by silica gel chromatography (eluent: 040% EtOAc / hexane) to provide 8-isopropyl-2-(trifluoromethyi)-4H-pyrido[l,2-a]pyrimidin-4-one (350 mg, 40% yield) as off white solid, LC / MS (ESI+) m / z = 2.57.1 [M+H]4. !H NMR (400 MHz, DMSO-d6) 3 8.95 (dd, J=7.4, 3.2 Hz, 1H), 7,71 - 7.66 (m, 1H), 7.50 (dd, 1=7.4, 1.9 Hz, 1H), 6.74 (d, J=2.4 Hz, 1H), 3.10 (h, 1=6.9 Hz, 1H), 1.28 (d, 1=6.9 Hz, 6H). Step 2: 3-IodO"8"isopropyL2-(trifluoromethyl)”4H-pyrido[l,2-a]pyrimidin"4-one, The title compound was prepared using the procedure described for Intermediate 1 B, Step 2 with the following modification: Step 2 was performed with 8-isopropyl-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI4) m / z = 383.0 [M+H]+. JH NMR (400 MHz, DMSO-d6) 3 8.96 (dd, J=7.3, 2.8 Hz, 1H), 7.72 (d, 1=2.0 Hz, TH), 7.56 (dd, 1=7.4, 2.0 Hz, 1H), 3.13 (p, 1=6.8 Hz, 1H), 1.29 (d, 1=6.9 Hz, 6H). -86- Intermediate 1-N 3-Bromo-8-(methoxy-d3)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one Intermediate 1-Q Step 1: 8-(Methoxy-d3)-2-(trifluoromethyI)-4H-pyrido[l,2-ajpyrimidin-4-one. 5           lodomethane-ds (0.5 ml, 7.8 mmol) was added to a reaction mixture of 8-hydroxy~2- (trifiuoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.60 g, 2.6 mmol. Intermediate 1-Q) and cesium carbonate (1.3 g, 3.9 mmol) in DMF (14 ml) at 0°C. The reaction mixture was stirred at rt. After Ih, the reaction mixture was diluted with water and EtOAc. The organic layer was separated, washed with water and brine, dried over Na?SO4 and concentrated in 10 vacuo. The erode residue was purified by silica gel chromatography (eluent:0-100% EtOAc,'heptane) to afford 8-(metiioxy-d3)-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidm-4-one as an off-white solid. LC / MS (ESC) m / z - 248.0           NMR (400 MHz, CDCi3) 8 6.61 (s, IH) 6.91 (dd, 1===7.88, 2.70 Hz, IH) 7.04 (d, 1===2..70 Hz, IH) 8.96 (d, 1==7.88 Hz, IH). Step 2: 3-Bromo-8-(methoxy-d3)-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one. 15           The title compound was prepared using the procedure described for Intermediate 1- C, Step 2 with the following modification: Step 2 was performed with 8-(methoxy-d3)-2-(trifluoromethyl)-4H-pyrido[l,2.-a.]pyrimidin-4~one. LC / MS (ESH) m / z = 32.6 / 328 [M+H]’. !HNMR (400 MHz, DMSO-ds) 6 7.25 (dd, 1=7.88, 2.70 Hz, IH) 7.31 (d, 1=2.70 Hz, IH) 8.91 (d, 1=7.88 Hz, IH). Intermediate 1-0 3-Brom o-8-methoxy-2-(trifluoromethyl)pyrimido [1,2-a] pyrimidin-4-one Step 1-1 and Step 1-2: 3-Bromo-8-methoxy-2-(triflMoromethy0pyriniido[l,2- 5 a]pyrmiidin-4-one. A reaction mixture of 4-methoxypyrimidin-2-amine (6.0 g, 48 mmol, Ark Pharm) and 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (26 ml.,, 144 mmol) in acetic acid (30 ml.,) was heated to reflux for 18 h. The reaction mixture was cooled to rt and bromine (2.5 mL, 48 mmol) was added dropwise and stirring was continued for at rt for 1 h. The reaction mixture 10 was concentrated in vacuo and the residue was treated with water, satd MaHCOj solution, and EtOAc. The organic layer was separated and concentrated under reduced pressure. The crude residue was purified silica gel chromatography (eluent: 0-50% EtOAc / heptane to afford 3-bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[l,2-a]pyrimidin-4-one (1.0 g, 3.2 mmol, 7% yield). LC / MS (ESI+) m / z - 324.0 / 326.0 [M+Hf. NMR (400 MHz, CDCh) 15    5 9.07 (d, J 7.A3 Hz, 1H), 6.82 (d, 1 7.63 Hz, 1H), 4.23 (s, 3H). Intermediate 1-P 3-Bromo-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one Step 1 Step 2 Steps 1 and 2 were performed according to the synthetic procedure described in 20   WO2008097991. LC / MS ASH m / z = 295.0 [M+H]+. - 88 - Intermediate 1-Q 8-Hydroxy-2-(trifluoroniethy!)-4H-pyrido[l,2-a]pyriniidin-4-one Step 1 Step 1: 8-Hydroxy-2-(trifluoromethyl)-4H-pyrido[l,2-aJpyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-A, Step 1 with the following modification: Step 1 was performed with 2-aminopyridin-4-ol (Combi-Blocks Inc.). LC / MS (ESP) m / z = 231.0 1M H T. Intermediate 1-R 3-Bromo-8-(methoxy-d3)-2-(trifluoromethyI)-4H-pyriniido[l,2-a]pyrimidiii-4-one Step 1: 4-(Methoxy-d3)pyrimidin-2-amine. MeOH-d4 (0.41 ml,, 10 mmol) was added dropwise to a suspension of sodium hydride (60% in mineral oil, 0.43 g, 10 mmol) in THF. The suspension was stirred for 10 mins and a solution of 2-amino-4-chloropyrimidine (1.0 g, 7.7 mmol, Asia Tech, Inc.) in 15 THF was added slowly. After completed addition the reaction mixture was stirred at rt for 12 h, diluted with water and extracted with EtOAc. lire organic phase was concentrated in vacuo to give 4-(methoxy-d3)pyrimidin-2-amine (0.81 g, 6.3 mmol, 82% yield). The crude -89- product was used in the next step without further purification. LC / MS (ESI4) m / z ::: 129.2 |M Hi . Step 2: 8-(Methoxy-d3)-2-(trifluoromethyi)-4H-pyrimido[l,2-ajpyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-C, Step 1 with the following modification: Step 1 was performed with 4-(methoxy-d3)pyrimidin-2-amine (0.8 g, 6.3 mmol) and 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (1.85 mL, 12.6 mmol). LC / MS (ESL) rn / z - 249.1 i M • I f | . !HNMR (400 MHz. CDCh) 8 9.06 (d, 1 7.67 Hz, 1H), 6.76 (d, 1==7.67 Hz, 1H), 6.71 (s, 1H). Step 3: 3-Bromo-8-(methoxy-d3)-2-(trifiuoromethyI)-4H-pyrimido|l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-A, Step 2 with the following modification: Step 2 was performed with 8-(methoxy-d3)-2-(trifluoromethyl)“4H-pyrimido[l,2-a]pyrimidin~4-one. LC / MS (ESI+) m / z == 327.0 / 329.0 |M Hi . !H NMR (400 MHz, DMSO-d6) 8 9.06 (d, J 7.67 Hz, 1H), 7.12. (d, 1==7.67 Hz, 1H). Intermediate 1-S 3~Bromo-2-(fluoromethyl)~8-methoxy-4H-pyrido[l,2-a]pynmidm-4~one Step 1                               Step 2 Step 1: 2-(FIuoromethyI)-8-methoxy-4H-pyrido|l,2-a]pyrimidin-4-one. A reaction mixture of 2-amino-4-methoxypyridine (0.5 g, 4.0 mmol, Combi-Blocks, Inc.) and ethyl 4-fluoro-3-oxobutanoate (1.1 g, 7.3 mmol, HCH Pharma) was heated to 120°C. After 20 min, methane sulfonic acid (0.5 ml, 8 mmol) was added. Heating was continued for 1 h. The reaction mixture was cooled to rt and treated with CH2Q2 (20 mL) and water (40 mL). The pH was adjusted to pH-14 by dropwise addition of 5M NaOH solution. The organic phase was separated, washed with brine (5 mL), dried over MgSCL, - 90 - then concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 0-40% (3:1 EtOAc / EtOH) / heptane) to afford 2-(fluoromethyl)-8-methoxy~4H-pyrido[l,2-a.]pyrimidin-4-one (40 mg, 0.19 mmol, 5% yield) as a white solid, LC / MS (ESI+) m / z =209.1 i M MT. Tl NMR (400 MHz, CDCh) 5 8.93 (d, 1=7 46 Hz, 1H), 6.77-6.83 (m, 2H), 6.40-6.45 (m, 1H), 5.28 (t, 1=46.60 Hz, 3H), 3.96 (s, 3H). Step 2: 3-Bromo-2~(fiuoromethyl)-8-methoxy-4H-pyndo[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-C, Step 2 with the following modification: Step 2 was performed with 2-(fluoromethyl)-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI / ) m / z = 287.0 / 289.0 [M+H]+. TI NMR (400 MHz, CDC10 8 8.95 (d, J 7.XH Hz, 1H), 7.07 (d, J 2.49 Hz, 1H), 6.91 (dd, 1=2.49, 7.88 Hz, 1H), 5.53 (d, 1=46.65 Hz, 2H), 3.98-4.01 (m, 3H). Intermediate 1-T 3-Brom o-2-ethy I-8-methoxy-4H-pyrido [ 1,2-a] pyrimidin-4-one Step 1: 2-EthyI-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-C, Step 1 with the following modification: Step 1 was performed with methyl 3-oxopentanoate (TCI America). LC / MS (ESL) m / z = 205.1 [M+H]+. 3H NMR (400 MHz, CIX L) 8 8.90 (dd, 1=8.0, 1.1 Hz, 1H), 6.90 - 6.85 (m, 1H), 6.77 (ddd, 1=7.9, 2.7, 1.1 Hz, 1H), 6.19 (d. 1=1.1 Hz, 1H), 3.96 (d, J 1.2 Hz, 3H), 2.67 (qd, 1=7.6, 1.1 Hz, 2H), 1.31 (td, 1=7.6, 1.2 Hz, 3H). Step 2: 3-Bromo-2~ethyl~8-methoxy-4H-pyrido[l,2~a]pyrimidin-4~one. The title compound was prepared using the procedure described for Intermediate 1-C, Step 2 with the following modification: Step 2 was performed with 2-ethyl-8-methoxy- -91 - 4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI ) m / z - 283.0 | M T H . !H NMR (400 MHz. CUCL) 8 8.89 (L J 7.7 Hz, 1H), 6.86 (dd, J 7.2. 2.8 Hz, 1H), 6.80 (dq, J 7.8. 2.7 Hz, 1H), 3.97 (d, 1===4.0 Hz, 3H), 2.91 (p, 1==7.4 Hz, 2H), 1.31 (td, 1==7.4, 5.2. Hz, 3H). Intermediate 1-U 3-Bromo-2~cydopropyI-8-meth0xy-4H-pyndo[l,2-a]pyrimidm-4-one Step 1: 2-CydopropyI-8-methoxy-4H-pyrido[l,2-a]pyrimidm-4-one. The title compound was prepared using the procedure described for Intermediate 1 S, Step 1 with the following modification: Step 1 was performed with methyl 3-cyclopropyl-10 3-oxopropanoate (Accela ChemBio Inc.). LC / MS (ESF) m / z = 217.2 [M+H]+. Step 2: 3-Bromo-2~cydopropyl-8-methoxy~4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-C, Step 2 with the following modification: Step 2 was performed with 2-cyclopropyl-8-methoxy-4H“pyrido[l,2-a]pyrirnidin-4-one. LC / MS (ESI4) m / z ==295.0 / 297.0 [M+H]+. 15 Intermediate 1-V 3-Bromo-8~(difhwromethoxy)-2-(trifluoromethyll)-4H~pyrido[l,2-a]pyrimidin-4-one intermediate 1-Q Step 1 Step 2 -92- Step 1: 8-(Difluoromethoxy)-2-(trifluoromethyi)-4H-pyrido[l,2-a]pyrimidin-4-one. Difluoromethyl trifluoromethanesulfonate (0.4 g, 2.2 mmol, prepared according to procedure described in Levin et al., Journal of Fluorine Chemistry 130 (2009) 667-670) was added to a suspension of 8-hydroxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.1 g, 0.4 mmol. Intermediate 1-Q) and potassium hydroxide (0.29 g, 5.2 mmol) in acetonitrile (2 ml). Ilie reaction mixture was stirred for 10 minutes at it. The reaction was quenched by the addition of saturated ammonium chloride solution. The reaction mixture was diluted with EtOAc and water. The organic phase was separated, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure. The crude residue was dissolved in EtOAc and treated with 1 IN NaOH. The organic layer was washed with additional IN NaOH, followed by saturated ammonium chloride and brine. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure to afford 8-(difluoromethoxy)-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one (0.1 g, 0.36 mmol) (combined yield). MS (ESI') m / z ::: 281.0 [M+H]+. Step 2: 3-Bromo-8-(difIuoromethoxy)-2-(trifluoromethyl)-4H~pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-A, Step 2 with the following modification: Step 2 was performed with 8-(difluoromethoxy)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 358.8 [M+H]4. 'HNMR (400 MHz, CD2C12) 5 6.98 - 7.38 (m, 1H) 7.38 - 7.42 (m, 1H) 7.80 (d, J=7.67 Hz, 1H) 8.99 (dd, 1=7.26, 1.04 Hz, 1H). Intermediate 1-W 3-Bromo-8-methoxy-2-methyI-4H-pyrido[l,2-a]pyrimidin-4-oiie Step 1 Step2 -93 - Step 1: 8-Methoxy-2-methyl-4H-pyrido[l,2-a]pyriimdin-4-one. The title compound was prepared using the procedure described for Intermediate 1-C, Step 1 with the following modification: Step 1 was performed with methyl acetoacetate, LC / MS (EST) m / z =191.2 [M+H]4. Step 2: 3-Bromo-8-niethoxy-2-methyl-4H-pyrido[l,2-a|pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-C. Step 2 with the following modification: Step 2 was performed with 8-methoxy-2-methyl-4H-pyndo[l,2-a]pyriinidm-4-one. Tl NMR(400 MHz, CDC13) 8 8.91 (d, J=7.88 Hz, 1H), 6.86 (d, J 2.40 Hz, 1H), 6.82 (dd, J 7.88. 2.70 Hz, 1 H), 3.97 (s, 3 H), 2.62 (s, 3 H). Intermediate 1-X 3-Bromo~8-£yc!opropyI-2~(trifhsoromethyl)-4I-I-pyrido[l,2-a]pyrimidin-4-one. Step 1: 8-CyclopropyI-2-(trifIuoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-C, Step 1 with the following modification: Step 1 was performed with 4-cyclopropylpyridin-2-amine (ArkPharm). LC / MS (EST) m / z =255.1 | M M j . Step 2: 3-Bromo-8-cydopropyl-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-A, Step 2 with the following modification: Step 2 was performed with 8-cyclopropyl-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one. LC / MS (ESH) m / z = 332.9 [M+HJVH NMR {( IX L. 400 MHz) 8 8.98 (d, J 7.5 Hz, 1H), 7.44 (d, 1=1.9 Hz, 1H), 7.02 (dd, J 7.5. 1.9 Hz, 1H), 2.02-2.09 (m, 1H), 1.28-1.35 (m, 2H), 0.96-1.09 (m, 2H). ..94.. Intermediate 1-Y 8-FIuoro-3dodo-2-(triflMoroniethy0-4H-pyrido[l,2-a]pyrimidin-4-one Step 1: 8-FIuoro-2-(trifhioromethyi)-4H-pyrido[l,2-a]pyrimidiii-4-one. 5            Potassium fluoride (0.3 g, 5.2. mmol) was added to a solution of 8-bromo-2- (trifluorometiiyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.5 g, 1.7 mmol. Intermediate 3-C) in DMSO (5 mL) under nitrogen atmosphere. 18-Crown-6 (23 mg, 0.085 mmol) was added and the resulting reaction mixture was heated at 100°C for 6h. The reaction mixture was cooled to it and quenched by the addition of ice (10 g). Stirring was continued for 15 min and the 10 resulting precipitate was filtered off. The solid was washed -with water (3 x 5 mL) and dried under reduced pressure to afford 8-fluoro-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (0.3 g, 76% yield). LC / MS (ESI ) m / z - 233.1    H|\ NMR(400 MHz, CDCL) 6 9.15 (dd, J-8.0, 6.2 Hz, 1H), 7.44 (dd, L8.5, 2.8 Hz, 1H), 7.14 (ddd, J 8.6. 6.2, 2.8 Hz, 1H), 6.77 (s, 1H). 15 Step 2: §-Fluoro-34odo-2-(trifluoromethyl)-4I-I-pyridoJl,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Step 2. was performed with 8-fluoro-2-(trifluoromethyl)-4H-pyrido[l,2~a]pyrimidin-4-one. LC / MS (ESI+) m / z = 359.1 [M+HJL lH NMR (400 MHz, DMSO-d6) 5 9.13 - 9.08 (m, 1H), 7.86 (dd, J-9.2, 2.8 Hz, 1H), 7.63 - 7.57 20    (m, 1H). -95 - Intermediate 1-Z 3-Iodo-8~(methyLd3)-2-(trifluoromethyI)-4H~pyrido[l,2-a]pyrimidin-4-one Br CoC^, Mg, CD3I CF3 benzene. Et2O D3C Step 2 Intermediate 3-C Step 1 Step 1: 8-(MethyI-d3)-2-(trifluoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one. Cobalt(ll) chloride (0.2 g, 1.5 mmol) was added to a solution of 8-bromo-2-(trifluoromethyl)-4H-pyrido[L2-a]pyrimidm-4~one (1.0 g, 3.4 mmol, Intermediate 3-C) in benzene (15 mL) at rt under nitrogen atmosphere. A separately prepared solution consisting of magnesium turnings (0.33 g, 13.7mmol) and tride uterom ethyl iodide (0.15 g, 10.2 mmol) in diethyl ether (10 mL), was added dropwise at rt. The reaction mixture was heated to 75°C for 2h. The reaction mixture was cooled to room temperature and quenched by addition of aqueous hydrochloric acid (1.5 N, 10 mL). After 10 min, the pH of the reaction mixture was adjusted to pH === 8 by addition of NaHCO;,, followed by dilution with ethyl acetate (25 mL). The mixture was filtered through a pad of celite and washed with ethyl acetate (3x5 mL). The organic layer was separated, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (eluent: 100% DCM) to provide 8-(methyI-d3)-2-(trifluoromethyl)-4H-pyrido[l.,2-a]pyrimidm-4-one (0.32 g, 40%) as a yellow solid. LC / MS (ESL) m / z - 232.2 [M+H]+. ‘H NMR (400 MHz, CDCh) 8 9.01 (d, J 7.3 Hz, 1H), 7.62 (d, J 1.8 Hz, 1H), 7.14 (dd, 1==7.3, 1.9 Hz, 1H), 6.74 (s, 1.H). Step 2: 3-Iodo-8-(methyl-d;0-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 w'ith the following modification: Step 2 was performed -with 8-(methyl-d;,)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one. LC / MS (ESI+) m / z == 358.0 [M+H]+. Tl NMR (400 MHz, CDCL) 8 9.03 (d, J 7.3 Hz, 1H), 7.64 (d, 1 =1.9 Hz, 1H), 7.19 (dd, 1====7.3, 1.8 Hz, 1H). - 96 - Intermediate 2-A 2-(4-((2,2-DifluorocydopropyI)methoxy)phenyI)-4,4,5,5-tetr am ethyl-1,3,2-dioxaborokme Step 1: l-((2^-DifluorocydopropyI)methoxy)-4-iodobenzene. DIAD (3.6 g, 18 mmol) was added drop-wise to a stirred solution of 4-iodophenol (3.4 g, 15 mmol) and triphenylphosphine (4.7 g, 18 mmol) in tetrahydrofuran (34 mL) under nitrogen atmosphere at 0°C. After 10 nun, (2,2-difluorocyclopropyl)methanol (1.5 g, 14 mmol) was added drop-wise and the reaction mixture was allowed to warm to it and stirred further for 16h. Ure reaction was quenched by addition of ice water (100 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were dried over NazSO^ filtered and concentrated under reduced pressure. The crude material was adsorbed onto a plug of silica gel and purified by silica gel chromatography (eluent: 0-3% of ethyl acetate / hexane) to afford 1-((2,2-difluorocyclopropyl)methoxy)-4-iodobenzene (1.8 g, 5.8 mmol, 42% yield). LC / MS (ESI+) m / z = 311.0 [M+H]+. ’H NMR (400 MHz, DMSO-de) 8 7.62 - 7.56 (m, 2H), 6.84 - 6.78 (m, 2H), 4.12 (ddd, 1=10.3, 6.6, 3.1 Hz, 1H), 3.95 (ddd, 1=10.6, 8.5, 1.8 Hz, IH), 2.26 - 2.14 (m, IH), 1.71 (tdd, 1=12.1, 7.9, 4.8 Hz, IH), 1.50 - 1.41 (m, IH). Step 2: 2-(4-((2,2-Difluorocydopropyi)methoxy)phenyl)-4,4,5,5-tetramethyI-l,3,2-dioxaborolane. A resealable vial was charged with 1-((2,2-difluorocyclopropyl)methoxy)-4-iodobenzene (1.6 g, 5.2 mmol), DMF (10 mL), bis(pinacolato)diboron (1.6 g, 6.2 mmol), and potassium acetate (2.0 g, 21 mmol). The reaction mixture was purged with nitrogen for 15 min and Pd(dppf)C12 (0.38 g, 0.52 mmol) was added. The reaction mixture was heated to 90°C for 16h. lire reaction mixture was filtered through a pad ofcelite and the filtrate was -97- concentrated under reduced pressure. The crude material was purified by silica gel chromatography (eluent: 0-5% ethyl acetate / hexane) to afford 2-(4-((2,2-Difhiorocycfopropyl)methoxy)phenyl)-4,4,5,5~tetramethyl-l,3,2-dioxaborolane (950 mg, 60% yield). TlNMR (400 MHz, DMSO-d6) 5 7.64 - 7.59 (m, 2H), 6.97 (dd, 1=8.7, 2.6 Hz, 2H), 4.17 (d, J K 1 Hz, 1H), 4.00 (t, J 9.2 Hz, 1H), 2.25 (s, 1H), 1.74 (d, 1=9.1 Hz, 1H), 1.52 - 1.44 (m, 1H), 1.30 - 1.27 (m, 12H). Intermediate 2-B 2-PhenyI-5-(4,4,5,5-tetramethyI-l,3,2-dioxaboroIan~2-y!)oxazoIe AIBM, MBS CCI4 Step 1 n-BuLi, (j-PrO)3B, Pinacol, AcOH, THF Step 2 Step 1: 5-Bromo-2-phenyIoxazoL NBS (19 g, 106 mmol) and AIBN (0.67 g, 4.0 mmol, SpectroChem) were added consecutively to a solution of 2-phenyl-4,5-dihydrooxazole (6.0 g, 41 mmol, Arbor) in carbon tetrachloride (60 mL). The reaction mixture was heated to 85°C for 2h. The reaction mixture was cooled down to rt and filtered through a pad of celite. The filtrate was concentrated under reduced pressure. The crude material was purified by silica gel chromatography (eluent: 0-5% of ethyl acetate / hexane) to afford 5-bromo-2-phenyloxazol (4.2 g, 46% yield). LC / MS (ESH) m / z = 224.0 |M • Hi . 'HNMR(400 MHz, CDCh) 8 8.05 - 7.99 (m, 2H), 7.52 - 7.46 (m, 3H), 7.13 (d, 1=1.4 Hz, 1H). Step 2: 2-PhenyI-5-(4,4,5,5-tetramethyI-l,3,2-dioxaboroian-2-yl)oxazole. N-butyl lithium (1.6 M in hexane, 0.61 mL, 0.982 mmol) was added to a solution of 5-bromo-2-phenyloxazol (200 mg, 0.89 mmol) in tetrahydrofuran (6 mL) at -78CC under nitrogen atmosphere. The reaction mixture was stirred at -78°C for 10 min, followed by the -98- addition of triisopropyl borate (201 mg, 1.1 mmol). The reaction mixture was stirred for 30 min at -78°C and allowed to warm to rt. After 30 min, 2,3-dimethylbutane-2,3-diol (127 mg, 1.1 mmol) and acetic acid (61 pL, 1,1 mmol) were added and stirring was continued at rt for Ih. The reaction mixture was concentrated under reduced pressure to get a crude residue 5    (400 mg), which was used without further purification. Intermediate 2-C 2-(4-(2,2-Difluoroethoxy)phenyl)-4,4,5,5~tetramethyl-l,3,2-dioxaborolane Step 1: 2-(4-(2,2-Difluoroethoxy)phenyI)-4,4,5,5-tetramethyI-l,3,2-dioxaboro!ane. 10           A mixture of 4-hydroxyphenylboronic acid pinacol ester (1.0 g, 4.5 mmol), dimethyl sulfoxide (20 mL), cesium carbonate (2.2 g, 6.8 mmol) and l,l-difluoro-2~iodoethane (1.2 ml,, 13.6 mmol, Matrix) was heated to 75°C for 2 h. The reaction mixture was diluted with EtOAc and water. The organic phase was separated, dried overNazSCh and concentrated in vacuo. The crude residue was purified by silica gel chromatography (eluent: 0-50% 15    EtOAc / heptane) to obtain 2-(4-(2,2-difluoroethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (1.18 g, 4.15 mmol, 91% yield). LC / MS (ESI4) m / z = 285 [M+H]2 *H NMR (400 MHz, CDCh) 8 1.33 (s, 12H) 4.11 - 4.31 (m, 2H) 5.86 - 6.27 (m, IH) 6.91 (d, .1=8.71 Hz, 2H) 7.77 (d, 1=8.71 Hz, 2H). .99. Intermediate 2-D 4-(4,4,5,5-Tetramethy!-l,3,2-dioxaborolan-2-yl)-l-(3,3,3-trifluoropropyl)pyrazoIe Step 1: 4-(4,4,5,5-Tetramethy!-l,3,2-dioxaboroIan-2-yl)-l-(3,3,3- 5 trifluoropropyOpyrazoie. A reseaiabie vial was charged with 4-pyrazoleboronic acid pinacol ester (500 mg, 2,6 mmol), acetonitrile (5 mL), cesium carbonate (1.7 g, 5.1 mmol), and l,l,l-trifluoro-3-iodopropane (604 pl, 5.15 mmol, Oakwood). The reaction mixture was heated to 80°C for 12 h. The reaction mixture was cooled to rt and filtered with EtOAc through a pad ofcelite. 10 The filtrate was washed with brine and the organic phase was dried over sodium sulfate. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: 0-60% EtOAc,'heptane) to afford 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-l-(3,3,3-trifluoropropyl)-lH-pyrazole (137 mg, 0.47 mmol, 18% yield). !HNMR (400 MHz, CDCI3) 5 1.32 (s, 13H) 2.74 (dt, 1=10.37, 7.36 Hz, 2H) 4.37 (t, 1=7.36 15 Hz, 2H) 7.71 (s, 1H) 7.81 (s, 1H). Intermediate 2-E 4-(4,4,5,5-TetramethyI-l,3,2-dioxaboroian-2-yl)-l-(4,4,4-trifkiorobutyl)pyrazoie Step 1 - 100 - Step 1: 4-(4,4,5,5-Tetramethyl-l,3,2-dioxaboroIan-2-yl)-l-(4,4,4-trifluorobutyI)pyrazote. A re sealable vial was charged with 4-pyrazoleboronic acid pinacol ester (500 mg, 2.58 mmol), acetonitrile (5 ml), potassium carbonate (0.53 g, 3.8 mmol), and 1,1,1-trifiuoro-4-iodobutane (0.7 ml, 5.2 mmol, Oakwood). The reaction mixture was heated to 65°C for 12 h. The reaction mixture was cooled to rt and partitioned between water and EtOAc. The organic phase was dried over sodium sulfate. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: 0-60% EtOAc / heptane) to afford 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-l -(4,4,4-trifluorobutyl)-lH-pyrazole (508 mg, 1.7 mmol, 65% yield). NMR (400 MHz, CDCh) 6 1.33 (s, 13H) 1.99 - 2.11 (m, 2H) 2.11 - 2.23 (m. 2H) 4.22 (t, J 6.46 Hz, 2H) 7.69 (s, 1H) 7.81 (s, 1H), Intermediate 2-F 2-(2-Fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-4,4,5,5-tetramethyLl,3,2-dioxaborohme Step 1: l-Bromo-2-fluoro-4-(2,2,2-trifluoroethoxy)benzene. 2,2,2-Trifluoroethyl iodide (4.6 ml, 47 mmol, Oakwood Products, Inc.) was added to a mixture of 4-bromo-3-fluorophenol (3.0 g, 15 mmol, Apollo Scientific, Ltd.) and potassium carbonate (4.3 g, 31 mmol) in DMF (30 ml). Tire reaction mixture was heated to 100°C for 12h. Additional 2,2,2-trifluoroethyl iodide (1.5 mL) was added and stirring was continued for 12 h. The reaction mixture was cooled rt and filtered with ethyl acetate through a pad of celite. The filtrate was washed with water, and brine and dried over NaiSO-?. The filtrate was concentrated under reduced pressure and the crude residue was purified by silica gel - 101 - chromatography(eluent: 0-20% ethyl acetate / heptane) to give 1 -bromo-2-fluoro-4-(2,2,2-trifluoroethoxy)benzene (3.75 g, 13.7 mmol, 87% yield). ’H NMR(CDCh, 400MHz): 5 = 7.48 (dd, 1=8.8, 7.8 Hz, 1H), 6.77 (dd, 1=9.8, 2.7 Hz, 1H), 6.67 (ddd, 1=8.9, 2.9, 1.2 Hz, 1H), 4.34 (q, 1=8.0 Hz, 2H). Step 2: 2~(2-Fluoro~4-(2,2,2~trifluoroethoxy)phenyl)-4,4,5,5~tetramethyl-l,3,2~ dioxaborolane. A resealable vial was charged with l-bromo-2-fluoro-4-(2,2,2-trifluoroethoxy(benzene (1.54 g, 5.64 mmol), bis(pinacolato)diboron (2.149 g, 8.46 mmol), potassium acetate (1.9 g, 19 mmol) and 1,4-dioxane (19 ml). The reaction mixture was purged for 5 min with argon, followed by the addition of Pd(dppf)Ch (0.46 g, 0.56 mmol, Strem). The reaction mixture was heated to 100°C for 18 h. The reaction mixture was cooled to rt and filtered with ethyl acetate through a pad of celite. The filtrate was concentrated under reduced pressure and the crude residue was purified by silica gel chromatography (eluent: 0-30% ethyl acetate / heptane) to give 2-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyi)-4,4,5,5-tetramethyl-i,3,2-dioxaborolane (1.37 g, 4.3 mmol, 76% yield). Tl NMR (Q'XVj, 400MHz): 6 7.69 (dd, J 8.3. 74 Hz, 1H), 6.72 (dd, 1 8.4. 2.3 Hz, 1H), 6.61 (dd, 1=10.6, 2.3 Hz, 1H), 4.35 (q, J8.0 Hz, 2H), 1.34 (s, 12H). Intermediate 2-G 1-(2,2,3,3,3-PentafluoropropyI)-4-(4,4,5,5-tetram ethyl-1,3,2-dioxaborolan-2-yl)-lH- pyrazoie - 102 - Step 1: 1-(2,2,3,3,3-Pentafluoropropyl)-4-(4,4,5,5-tetramethyI-l,3,2-dioxaboroian-2-y!)-IH-pyr azole. A resealable vial was charged 4-pyrazoleboronic acid pinacol ester (0.5 g, 2.6 mmol) potassium carbonate (0.7 g, 5 mmol), DMF (3 ml), and 2,2,3,3,3-pentafluoropropyl trifluoromethanesulfonate (1.0 g, 3.5 mmol, Matrix Scientific). The reaction mixture was heated to 80°C for 12h. The reaction mixture was cooled to rt and partitioned between water (70 mL) and EtOAc (70 mL). The organic layer was dried over sodium sulfate, filtered, and adsorbed onto a pad of silica gel. Purification by silica gel chromatography (eluent: 0-60% EtOAc / heptane) afforded 1-(2,2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-lH-pyrazole (289 mg, 0.9 mmol, 34% yield) which was carried forward in the next reaction without further purification, !H NMR (400 MHz, CDCh) 8 1.32 (s, 16H) 4.75 (t, 1=14.10 Hz, 2H) 7.80 (s, 1H) 7.84 (s, 1H). Intermediate 2-H 3-(4-(4,4,5,5-TetramethyI-l,3,2-dioxaborolan-2-yI)-lH-pyrazoI-l-yl)propanenitrile Nai, KgCOg, ACN Step 1 Step 1: 3-(4-(4,4,5,5-Tetramethyi-l,3,2-dioxaboroIan-2-yi)-lH-pyrazoI-l-yOpropanenitrile. 3-Bromo-propionitrile (2.1 g, 15 mmol, Combi-Blocks Inc.), sodium iodide (0.154 g, 1.03 mmol) and potassium carbonate (2.1 g, 15 mmol) were added consecutively to a suspension of 4-(4,4,5,5-tetramethyi-l,3,2-dioxaboroian-2-yl)-lH-pyrazole (2.0 g, 10.3 mmol, 1.0 eq.) in acetonitrile (20 ml.,). The reaction mixture was heated at 60°C for 12 h. Hie reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between water and ethyl acetate. The organic layer was washed with brine and dried over NaiSCK The filtrate was concentrated under reduced pressure to get the 3-(4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazol-l-yl)propanenitrile (2.5 g, 10.1 mmol, 98% yield) as a yellow' liquid which was used for next - 103 - step without further purification. LC / MS (ESI+) m / z::: 248.1 [M+H] \ SH NMR (400 MHz, DMSO-d6) 8 8.04 (s, 1H), 7.65 (s, 1H), 4.41 (t, J 64 Hz, 2H), 3.07 (t, J 6.4 Hz, 2H), 1.26 (s, 12H). Intermediate 2-1 5    2-(4-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan~2-yl)-lII-pyrazoi-l-yI) acetonitrile Nah KjCOj, ACM Step 1 Step 1: 2-(4-(4,4,5,5-TetramethyI-l,3,2-dioxaboroian-2-yl)-lH-pyrazoLl-yI) acetonitrile. Ilie title compound was prepared using the procedure described for Intermediate 2 H, Step 1 with the following modification: Step 1 was performed with 4-(4.4,5,5-tetramethyl - 10 l,3,2-dioxaborolan-2-yl)-lH-pyrazole (2.0 g, 10 mmol, Combi-Blocks Inc.) and 2- bromoacetonitrile (4.95 g, 41.2 mmol, Spectrochem). LC / MS (ESI+) m / z = 234.2 [M+H]+. SH NMR (400 MHz, CDCh) 3 7.85 (s, 2H), 5.10 (s, 2H), 1.33 (s, 12H). Intermediate 2-J l-(2,2-DifluoropropyI)-4~(4,4,5,5-tetramethyLl,3,2-dioxaborolan-2-yl)-lH~pyrazole 15 Step 1 Step 2 Step 1: 4-Bromo-l-(2,2-difiuoropropyl)-lH-pyrazole. A solution of diethylaminosulfur trifluoride (0.84 mL. 6.3 mmol) in DCM (2 mL) was added drop-wise to a solution of l-(4~bromo-lH-pyrazol-l-yl)propan-2-om (0.33 g, 1.6 mmol, Enamine Ltd) in DCM (10 mL) at -78°C. The reaction mixture was allowed to warm to room temp over the course of 12 h. Tire reaction mixture was cooled to 0°C and quenched by the addition of 1 N sodium thiosulfate (20 mL), followed by partitioning between EtOAc and water. The organic extract was washed with brine, dried over sodium sulfate, filtered, and adsorbed onto silica gel. Purification by silica gel chromatography (eluent: 0-100% EtOAc,'heptane) afforded 4-bromo-l-(2,2-difluoropropyl)-lH-pyrazole (220 mg, 0.98 mmol, 61% yield) of 4-bromo-l-(2,2-difluoropropyl)-lH-pyrazole. ;H NMR (400 MHz, CDCh) 5 1.57 (t, 1=18.66 Hz, 3H) 4.43 (t, 1=12.02 Hz, 2H) 7.51 (s, 1H) 7.53 (s, 1H). Step 2: l-(2,2-Difluoropropyl)-4-(4,4,5^-tetramethyI-l,3»2-dioxaborolan-2-yl)-lH-pyrazole. A resealable vial was charged with 4-bromo-l-(2,2-difluoropropyl)-lH-pyrazole (0.31 g, 1.4 mmol), bis(acetonitrile)dichloropalladium(II) (11 mg, 0.04 mmol, Strem) and 2-dicyclohexylphosphino-2,6'-dimethoxy-l,r-biphenyl (51 mg, 0.12 mmol, Strem). The vial was evacuated and backfilled with nitrogen. This procedure was repeated 3 times. Toluene (1.8 ml) was added, followed by pinacolborane (0.24 ml, 1.6 mmol) and triethylamine (0.48 ml, 3.4 mmol). Additional toluene (0.7 ml) was added. The reaction mixture was heated to 90°C for 12h. lire reaction mixture was filtered through a plug of silica gel and concentrated underpressure. The crude residue was purified by silica gel chromatography (eluent: 0-50% EtOAc / heptane) to afford 1 -(2,2-difluoropropyl)-4-(4,4,5,5-tetramethyI-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (164 mg, 0.6 mmol, 44% yield). TlNMR (400 MHz, CDCfi) 8 1.33 (s, 12H) 1.56 (m, 3H) 4.47 (t, 1=12.02 Hz, 2H) 7.79 (s, 1H) 7.81 (s, 1H). Intermediate 2-K 2-(FluoromethyI)-3-iodo-4~oxo-4H-pyrido[l,2~a]pyrimjdine-8-carbonitrile O O - 105 - Step 1: 2-(FIuoromethyl)-4-oxo-4H-pyridoJl,2-a]pyrimidine-8-carbmiitrile. Polyphosphoric acid (~700pL) was added to a suspension of ethyl 4-fluoro-3~ oxobutanoate (0.4 g, 2.7 mmol, HCH Pharma) and 2~aminopyridine-4~carbomtrile (0.32 mg, 2.7 mmol, Fluorochem), The reaction mixture was heated to 90°C for 6 h. The reaction mixture was poured into 50 ml of water and extracted with EtOAc (2x). The organic layer was dried, filtered and concentrated under reduced pressure. The residue was dissolved in THF (15 mL) and pyridine (0.3 mL, 4 mmol) was added followed by trifluoroacetic anhydride (370 uL, 2.7 mmol). The resulting mixture was stirred at room temperature for 1 h, then quenched with water and extracted with EtOAc. Ure organic layer was dried, filtered and concentrated and the residue was purified by silica gel chromatography (eluent: 50% EtOAc / cyclohexane) to give 2-(fluoromethyl)-4-oxopyrido[l,2-a]pyrimidme-8-carbonitrile (290 mg, 1.43 mmol, 53% yield). LC / MS (ESP) m / z == 204.0 [M+H]+. Td NMR (400 MHz, DMSO-d6) 8 5.34 - 5.61 (d, 2H) 6.55 - 6.61 (s, 1H) 7.46 - 7.60 (d, 1H) 8.34 - 8.43 (s, 1H) 8.93 - 9.01 (d, 1H). Step 2: 2-(FIuoromethyI)-3-iodo-4-oxo-4H-pyrido[l,2~a]pyrimidine-8-carbonitriIe. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Step 2 was performed with 2-(fluoromethyl)-4-oxo~4H-pyrido[l,2-a]pyrimidine-8~carbonitrile. LC / MS (EST) m / z = 402.1 [M+H] \ lH NMR (400 MHz, DMSO-d6) 8 5.43 - 5.64 (d, 2H) 7.64 (d, 1=7.48, 1H) 8.49 - 8.54 (s, 1.H) 8.96 - 9.03 (d, 1H). Intermediate 2-L (2-Fluoro-4-(2,2,2-trifluoroethoxy)phenyl)boronic acid Intermediate 2~F - 106 - Step 1: (2-Fluoro-4-(2,2,2-trifluoroethoxy)phenyl)boroiiic add. Sodium periodate (0.13 ml, 2.3 mmol) was added to a solution of 2-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (0.25 g, 0.78 mmol. Intermediate 2-F) in THF:water concentrated under reduced pressure to afford (2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)boronic acid. ’H NMR (400 MHz, DMSO-dJ 5 8.02 (s, 1H) 7.49 - 7.81 (in, 1H) 6.76 - 6.97 (m, 2H) 4.81 (q, J 8.85 Hz, 2H). (1:1, 10 ml) and IN hydrochloric acid (5 ml). After 20 min, the reaction mixture was partitioned between EtOAc and water. The organic layer was washed with brine, dried over magnesium sulfate and Intermediate 2-M 4-(4,4,5,5-TetramethyI-l,3,2-dioxaborolan-2-yl)-l-(2,2,2-trifluoroethyl)-lH-pyrazole Step 1: 4-(4,4,5,5-Tetramethyl-l,3,2-dioxaboroian-2-yl)-l-(2,2,2-trifluoroethyI)-lH-pyrazole. 2,2,2-Trifluoroethyl triflate (0.37 ml, 2.6 mmol, Oakwood Products) was added to a mixture of 4-pyrazoleboronic acid pinacol ester (0.25 g, 1.3 mmol), potassium carbonate (0.27 g, 1.9 mmol), and acetonitrile (2.6 ml). The reaction mixture was heated to 65°C for 12h. The reaction mixture cooled to rt and partitioned between water (70 mL) and EtOAc (70 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography afforded 4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l-(2,2,2-trifluoroethyl)-lH-pyrazo1e (133 mg, 0,48 mmol, 37% yield). 4I NMR (400 MHz, CD2C12) 5 1.30 (s, 13H) 4.74 (q, 1=8.41 Hz, 2H) 7.75 (s, 1H) 7.79 (s, 1H). Intermediate 2-N 2-(3-Chloro-4-(2,2,2-trifluoroethoxy)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane Step 1: 4-Bromo-2-chloro-l-(2,2,2-t:rifluoroethoxy)benzene. 1,1,1-Trifluoro-2-iodoethane (4.2 ml, 43 mmol, Oakwood Products, Inc.) was added to a mixture of 2-chloro-4-bromophenol (3.0 ml, 14 mmol) and potassium carbonate (4.0 g, 29 mmol) in DMF (30 ml). The reaction mixture was heated to 100°C for 12h. The reaction mixture was cooled to rt and filtered with EtOAc through a pad of celite. lire filtrate was washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 0-20% ethyl acetate / heptane) to give 4-bromo-2-chloro-1-(2,2,2-trifluoroethoxy)benzene (2.8 g, 9.7 mmol, 67% yield). Tl NMR (CDCk 400MHz): 8 - 7.55 (d, J 2.3 Hz, 1H), 7.36 (dd, J 8.7. 2.4 Hz, 1H), 6.86 (d, J X.X Hz, 1H), 4.38 (q, 1==8.0 Hz, 2H) Step 2: 2-(3-Chlmm-4-(2,2,2-trifluoroethoxy)phenyI)-4,4,5,5-tetramethyI-l,3,2-dioxaborolane. A mixture of 4-bromo-2-chloro-l-(2,2,2-trifluoroethoxy)benzene (1.7 g, 6.0 mmol), bis(pinacolato)diboron (2.3 g, 9.0 mmol), potassium acetate (2.1,21 mmol) and Pd(dppf)Ch (0.49 g, 0.6 mmol, Strem) in dioxane (20 rnl) was purged with argon for 5 minutes. The reaction mixture was heated to 110°C for 12h. The reaction mixture wras cooled tor rt and filtered with EtOAc through a pad of celite. The filtrate was concentrated under reduced pressure and the residue was purified by silica gel chromatography (eluent: 0-20% ethyl acetate / heptane) to give (1.38 g, 4.1 mmol, 68% yield). TlNMR (CDCh, 400MHz): 6 = 7.77 (d, 1==1.6 Hz, 1H), 7.59 (dd, 1 8.1, 1.5 Hz, 1H), 6.85 (d, J 8.2 Hz, 1H), 4.35 (q, 1===8.0 Hz, 2H), 1.26 (s, 12H). Intermediate 2-0 3-Bromo-2-f!uoro-6-(2,2,2-trifluoroethoxy)pyridine ******************************^^frOe»* K2CO3s dmf Step 1 Step 1: 3-Bnmio-2-fluoro-6-(2,2,2-trifluoroethoxy)pyridine. l,l,l-Trifiuoro-2-iodoethane (0.76 ml, 7.8 mmol, Oakwood Chemical, Estill, SC, USA) was added to a mixture of 3-bromo-2-fluoro-6-hydroxypyridine (500 nig, 2.6 mmol, Combi-Blocks, San Diego, CA, USA) and potassium carbonate (0.72 g, 5.2 mmol) in DMF (5 ml) under argon atmosphere. The reaction mixture was heated to 100°C for 12 hours. The reaction mixture was cooled to rt and filtered with EtOAc through a pad of celite. The filtrate was washed with water and brine, dried over NaAO.; and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 0-10% ethyl acetate / heptane) to give 3-bromo-2-fluoro-6-(2,2,2-trifluoroethoxy)pyridine (0.71 g, 0.91 mmol, 35% yield). LC / MS (ESF) m / z = 274.0 [M+H]+. Intermediate 2-P 2-Brom 0-5-(2,2,2-trifluoroethoxy)pyridine f3c^oh KOIBu Step 1 f3c Br Step 1: 2-Bromo-5-(2,2,2-trifiuoroethoxy)pyridme. A resealable vial was charged with 2,2,2-trifluoroethanol (0.42 ml, 5.7 mmol), potassium-terr-butoxide (IM in THF, 5.7 ml, 5.7 mmol), 2-bromo-5-fluoropyridine (1.0 g, 5.68 mmol) and THF (6 ml). The reaction mixture was heated to 70°C for 60 hours. Hie reaction mixture was cooled to ambient temperature and partitioned between water and EtOAc. The organic phase was dried over MgSO4 and concentrated m vacuo. The crude - 109 - residue was purified via silica gel chromatography (eluent: 0-10% EtOAc / heptane) to afford 2“bromO“5-(2,2,2-trifluoroethoxy)pyridine (150 mg, 0.59 mmol, 10% yield) as a solid. LC / MS (ESF) m / z = 256.0 | M • Hi . Intermediate 2-Q 5 5-Bromo-3-fluoro-2-(2,2,2-trifluoroethoxy)pyridine Step 1: 5-Bromo-3-fluoro-2-(2,2,2-trifluoroethoxy)pyridine. 1,1,1-Tri fluoro-2-iodoetbane (2.3 ml, mmol, Oakwood Chemical, Estill, SC, USA) was added to a mixture of 5-bromo-3-fluoropyridin-2-ol (1.5 g, 7.8 mmol, Combi-Blocks, 10 San Diego, CA, USA) and potassium carbonate (2.2 g, 15.6 mmol) in DMF (10 ml) under argon atmosphere. The reaction was heated to 100°C for 12 h. The reaction mixture was cooled to rt and filtered with EtOAc through a pad of celite. The filtrate was washed with water and brine, dried over Na?SO4 and concentrated under reduced pressure. The crude residue w as purified by silica gel chromatography (eluent: 0-10% ethyl acetate / heptane) to 15 give 5-bromo-3-flaoro-2-(2,2,2-triflaoroethoxy)pyridme (1.28 g, 4.67 mmol, 60% yield). LC / MS (ESC) m / z == 274.0 |M • Hi . Intermediate 2-R 5-Bromo-2-(2,2,2-trifluoroethoxy)pyridine KOtBu Step 1 r - 110 - Step 1: 5-Bromo-2-(2,2,2-trifiuoroethoxyjpyndine. The title compound was prepared using the procedure described for Intermediate 2P, Step 1 with the following modification: Step 1 was performed with 5~bromo~2-fluoropyndme. LC / MS (EST+) m / z - 255.8 [M+H]+ / '258.0 [M+2]+. 5 Intermediate 2-S (2-MethyM-(2,2,2-trifluoroethoxy)pheiiyl)boronic acid Step 2 KOAc, Dioxane Step 1: l-Bromo-2-methyi-4-(2,2,2-trifluoroethoxy(benzene. A vial was charged with 4-bromo-3-methylphenol (1g, 5.4 mmol), 1,1 ,l-trifluoro-2-10 iodoethane (4.5 g, 21.4 mmol, Oakwood), DMF (5 ml) and cesium carbonate (3.5 g, 10.7 mmol). The reaction mixture was heated to 60°C for 48h. The reaction mixture was cooled to rt and partitioned between EtOAc and water. The organic phase was separated, washed with water and brine, and dried over MgSO4. The filtrate was absorbed onto a pad of silica gel. Purification by silica gel chromatography (eluent: 0-10% (3:1 EtOAc / EtOH) / heptane) 15 provided 1-bromo-2-methyl-4-(2,2,2-trifluoroethoxy(benzene (1.1 g, 4.1 mmol, 76% yield) U SMR (CDC13, 400 MHz) 5 7.37 (d, 1 8.7 Hz, 1H), 6.77 (d, J 3.1 Hz, 1H), 6.58 (dd, 1=8.7, 3.1 Hz, 1H), 4.24 (q, J=8.2 Hz, 2H), 2.31 (s, 3H). - Ill - Step 2: 44,5d3-Tetramethy4-2-(2-methyL4-(2,2,2-trinuoroethoxy)phenyI)-l,3,2-dioxaborolane. The title compound was prepared using the procedure described for Intermediate 2-N, Step 2 with the following modification: Step 2 was performed with l-bromo-2-methyl-4-(2,2,2-trifluoroethoxy)benzene. TI NMR (CDC13, 400 MHz) 5 7.74 (br d, J S.3 Hz, IH), 6.64-6.79 (m, 2H), 4.29-4.40 (m, 2H), 2.53 (s, 3H), 1.31-1.38 (m, 12H). Step 3: (2-Methyi-4-(2,2,2-trifluoroethoxy)pheny!)boronic add. The title compound was prepared using the procedure described for Intermediate 2-L. Step 1 with the following modification: Step 1 was performed with 4,4,5,5-tetramethyl-2-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-l,3,2-dioxaborolane. !HNMR (DMSO-ds, 400 MHz) 8 7.83 (d, J 1 Hz, IH), 6.76-6.93 (m, 2H), 4.73 (q, J 8.9 Hz, 2H), 2.61-2.65 (m, 3H). Intermediate 2-T 8-ChIoro-3~iodo-2~(triflhwromethyI)-4II~pyrido[l,2~a]pyrimidm-4~one Step 1: 8-Chioro-2-(trifIuoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one. Concentrated hydrochloric acid (37%, 3.4 mL, 41 mmol) was added to a solution of 8-bromo-2-(trifluoromethyl)~4H-pyrido[l,2-a]pyrimidin-4-one (2.0 g, 6,8 mmol, Intermediate 3-C) hi acetonitrile (16 mL). The resulting mixture was then subjected to microwave irradiation at 100°C for 15 mins. Hie mixture was slowly quenched with saturated NaHCCh (200 mL) and extracted with EtOAc (2 x 200 mL). Ilie combined organic extracts were dried over MgSCh and concentrated under reduced pressure. Purification of the crude residue by silica gel chromatography (eluent: 0%-100% EtOAc / heptane) provided 8-chloro-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 249.1 Intermediate 34 - 112 - Hi . rHNMR (DMSO-dJ 5: 8.97 (d, J 7.7 Hz. 1H), 8.10 (d. J 2.1 Hz, 1H), 7.55 (dd, J 7.7. 2.3 Hz, 1H), 6.87 (s, 1H). Step 2: 8-Chloro-3-iodo-2-(tnfluoromethyI)-4H-pyTido[l,2-a|pynmidm-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Step 2 was performed with 8-chloro-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 374.9 [M+H]+. !H NMR (DMSO<16) 6 8.96 (d, .17.7 Hz, 1H), 8.10 (d, J 2.1 Hz, 1H), 7.59 (dd, J 7 7. 2.3 Hz, 1H). Intermediate 2-U 3-Iodo-2-(trifIuoromethy!)~8-vinyI-4H~pyrido [1,2-a] pyrimidin-4~one O Pd(PPh3)4, toluene uuuuuuuuuuuuuuuuuuuuu»Luuuuuuuuuuu^^                                   |           8          s| Step 1 Tributyl(vinyl)tin (0.90 g, 2.86 mmol) was added to a solution of 8-bromo-3~iodo~2-(trifiuoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (1.0 g, 2.38 mmol, Intermediate 3-1) in toluene (10 mL). Ilie reaction mixture was purged with nitrogen for 10 minutes and Pd(PPh3)4 (276 mg, 0.24 mmol) was added. The reaction mixture was heated to 110°C for 12h. The reaction mixture was concentrated under reduced pressure and the crude residue was purified by silica gel chromatography (eluent: 0-10% ethyl acetate / hexane) to afford 3-iodo-2-(trifluoromethyl)-8-vinyl-4H-pyrido [1,2-a] pyrimidin-4-one (400 mg, 46% yield). LC / MS (ESI+) m / z - 367.1 [M+H]+. !H NMR (400 MHz, DMSO-d6) 5 8.93 (d, 1=7.5 Hz, 1H), 7.91 (d, 1=1.8 Hz, 1H), 7.79 (dd, 1=7.6, 1.9 Hz, 1H), 6.96 (dd, 1=17.6, 10.9 Hz, 1H), 6.42 (d, 1=17.7 Hz, 1H), 5.82 (d, 1=10.9 Hz, 1H)- Intermediate 2-V 3-Bromo-8-methyI-2-(trifluoromethyl)-4H-pyrjdo[l,2-a]pyrimidin-4-one Step 1                             Step 2 Step 1: 8-Methyl-2-(trifluoromethyi)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-O, Step 1-1 with the following modification: Steps 1-1 was performed with 2-amino-4-methylpyridine. LC / MS (ESI+) rn / z - 229.9 j XI = U 5HNMR (400 MHz, CDCh) 5 8.99 (d, J 7.3 Hz, 1H), 7.60 (s, 1H), 7.14 - 7.09 (m, 1H), 6.72 (s, 1H), 2.54 (s, 3H). Step 2: 3-Bromo-8-methyL2-(trifIuoromethyl)-4II-pyrido[l,2-ajpyrimidm-4-one. 10           Tire title compound was prepared using the procedure described for Intermediate 1- O, Step 1-2 with the following modification: Steps 1-2 was performed with 8-methyl-2-(trifluoromethyl)-4H~pyrido[l,2~a]pyrimidin-4-one. LC / MS (ESH) m / z = 307.0 [M+H]+. Intermediate 2-W 3-Iodo-2,8-dimethoxy-4H-pyrido[l,2-aJpyrimidin-4-one 15 O 0 Step 1 Step 2 N H Step 3 Step 4 - 114 - Step 1: Ethyl 3-((4-methoxypyridm-2-yl)ammo)-3-oxopropaiwate.. A solution of ethyl malonyl chloride (3.9 ml, 30 mmol) in DCM (10 mL) was added dropwise to a solution of 2-amino-4-methoxylpyridine (2.5 g, 20 mmol, Combi-Blocks Inc.) in DCM (12 mL) and pyridine (18 ml) at 0°C. The reaction mixture was stirred at 0°C for 40 min. Water (40 mL) was added and the reaction mixture was stirred vigorously for 3 h at rt. Aqueous, saturated sodium carbonate was added and the organic layer was separated. The aqueous phase was extracted with DCM, the combined organic layers were dried over NajSO4 and concentrated in vacuo. The crude material was purified by silica gel chromatography (eluent: 0-25% (3:1 EtOAc / EtOH) / heptane) to provide ethyl 3-((4-methoxypyridin-2-yl)ammo)-3-oxopropanoate (1.54 g, 6.5 mmol, 32% yield). ‘HNMR (400 MHz, CDCL) 8 9.45 (br s, 1H), 8.09 (d, 1=5.80 Hz, 1H), 7.80 (s, 1H), 6.60 (dd, 1=2.28, 5.80 Hz, 1H), 4.25 (q, 1=7.05 Hz, 2H), 3.86 (s, 3H), 3.47 (s, 2H), 1.31 (t, J=7 15 Hz, 3H). Step 2: 2~Chloro~8-niethoxy-4H-pyrido[l,2-a]pynmidin-4~one. A mixture of ethyl 3-((4-methoxypyridin-2-yl)amino)-3-oxopropanoate (1.0 g, 4.3 mmol), phosphorous oxychloride (1.2 ml, 13.0 mmol), and polyphosphoric acid (0.17 ml, 4.3 mmol) was heated to 130°C for 16 h. The reaction mixture was cooled to rt, followed by addition of EtOH (4.3 mL). The reaction mixture was further heated at reflux for 30 min, then allowed to cool to rt. Tire reaction mixture was partitioned between EtOAc and brine. Tire aqueous layer was back extracted with EtOAc (- 2) and the combined organic layers were dried over NaiSOt. The filtrate was concentrated in vacuo and the residue was suspended in DCM (5 mL). The solid was filtered off and dried to give 2-chloro-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one (485 mg, 2.3 mmol, 53% yield) as a solid. LC / MS (ESI’) m / z = 211.1 [M+H]+. Step 3: 2,8-Dimethoxy-4H~pyrido[l,2-a]pyrimidin-4-one. Sodium methoxide (25 wt % in MeOH, 0.33 ml, 1.5 mmol) was added dropwise to a solution of 2-chloro-8-methoxy-4H-pyrido|T,2-a]pyrimidin-4-one (213 mg, 1.0 mmol) in acetonitrile (2 ml). The reaction mixture was stirred at rt for 2 h, followed by partitioning between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layers were dried overNa?SO4. The filtrate was concentrated to give 2,8-dimethoxy- - 115 - 4H-pyrido[l,2-a]pyrimidin-4-one (172 mg, 0.83 mmol, 82% yield) as an off-white solid. LC / MS (ESr) m / z == 207.2 |M Hi . Step 4: 3-Iodo-2,8-dimethoxy-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Steps 2 was performed with 2,8-dimethoxy-4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 333.0 [M+H]+. Intermediate 2-X 2-Ethoxy-3-iodo-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one Step 1: 2~Ethoxy-8~methoxy~4H-pyrido[l,2-a]pyrimidin-4-one. Sodmm ethoxide (254 mg, 0.78 mmol) was added to a solution of 2-chloro-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one (150 mg, 0.71 mmol, prepared according to method described for Intermediate 2-W, Steps 1 and 2) in acetonitrile (2.3 ml). The reaction mixture was stirred at rt for 1 h, followed by partitioning between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4. The filtrate was concentrated and the crude material was purified by silica gel chromatography (eluent: 0%-25% (3:1 EtOAc / EtOH) / heptane) to provide 2-ethoxy-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one (85 mg, 0.39 mmol, 54% yield) as a white solid. LC / MS (ESC) m / z = 221.1 %L % Step 2: 2-Ethoxy-3-iodo-8-methoxy-4H-pyrido[l,2-a]pyrimidm-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Steps 2 was performed with 2-ethoxy-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESL) m / z == 347.0 [M+H]+. Intermediate 2-Y 3-(4-Hydroxy-2-(trifluoromethyl)phenyl)-8-meth oxy-2-(tnfiuoromethyl)~4H-pyndo[l,2-a] pyrimidin-4-one Q OH SPhos Paliadacycie CS2CO3, Dioxane Intermediate 1-A          Step 1 10 Step 1: 3-(4-Hydroxy-2-(trifiuoromethyl)phenyi)-8-methoxy-2~(trifhwromethyl)-4H-pyrido[l,2-a|pyriniidm-4-one. The title compound was prepared using the procedure described for Method 4, Step 3 with the following modification: Step 3 was performed with 3-bromo~8-methoxy-2-(trifluoromethyi)-4H-pyrido[ l,2-a]pyrimidin-4-one (0.15 g, 0.46 mmol. Intermediate 1-A) and 4-hydroxy-2-(trifluoromethyl)phenylboronic acid (144 mg, 0.7 mmol, Aurum Pharmatech LLC). LC / MS (ESI4) m / z ~ 404.9 [M+H]+. lH NMR (DMSO-dt,, 400 MHz) 8 10.18-10.39 (m, 1H), 8.88 (d, 1=7.9 Hz, 1H), 7.31 (d, 1=2.7 Hz, 1H), 7.14-7.23 (m, 3H), 7.09 (d, 1=8.6 Hz, 1H), 4.05 (s, 3H). Intermediate 2-Z 3-(2-Chloro-4-hydroxyphenyl)-8-methoxy-2-(trifkioromethyI)-4H-pyrido|l,2-a]pyrimidin-4-one OH intermediate 1-A Step 1 - 117 - Step 1: 3-(2-Ch!oro-4-hydroxyphenyI)-8-methoxy-2-(trinuoromethyI)-4H-pyrido^l,2-a] pyrimidin-4-one. The title compound was prepared using the procedure described for Method 4. Step 3 with the following modification: Step 3 was performed with 3-bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one (1 g, 3.1 mmol, Intermediate 1-A) and 2-chloro-4-hydroxyphenylboromc acid (800 mg, 4.6 mmol, Combi-Blocks Inc.). LC / MS (ESF) m / z = 371.0 [M+H|+.   NMR(DMSO-d6, 400 MHz) 5 10.03 (br s, 1H), 8.89 (d, 1=7.9 Hz, 1H), 7.31 (d, 1=2.7 Hz, 1H), 7.21 (dd, 1=7.9, 2.9 Hz, 1H), 7.12 (d, 1=8.3 Hz, 1H), 6.93 (d, 1=2.3 Hz, 1H), 6.79 (dd, J 8.3, 2.5 Hz, 1H), 4.04 (s, 3H), 3.30 (s, 3H). Intermediate 3-A 3-(4-HydroxyphenyI)-8-methoxy-2~(trifIuoromethyl)-4H-pyrido[l,2~a]pyrimidiii-4~one Intermediate 1-A          Step 1 Step 1: 3-(4-Hydroxyphenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a] pyrimidin-4-one. The title compound was prepared using the procedure described for Method 4, Step 3 with the following modification: Step 3 was performed with 3-bromo-8-methoxy-2-(trifluoromethyi)-4H-pyrido[ l,2-a]pyrimidin-4-one (1 g, 3.1 mmol, Intermediate 1-A) and (4-hydroxyphenyl)boromc acid (0.63 g, 4.6 mmol, Combi-Blocks Inc.). LC / MS (ESI’) m / z = 337.0 [M+H]2 'HNMR (400 MHz, CDCh) 5 8.97 (d, 1=7.88 Hz, 1H), 7.14 (d, 1=8.2.9 Hz, 2H), 7 07 (d. 1=2.49 Hz, 1H), 6.94 (dd, 1=2.70, 7.88 Hz, 1H), 6.79 (d, 1=8.50 Hz, 2H), 6.47 (br s, 1H), 4.00 (s, 3H). Intermediate 3-B 3-(4-Hydroxyphenyl)-8-methoxy-2-(trjfluoromethyl)-4H-pyrimido[l,2-a]pyrimidin-4- one Intermediate 1-0 Step 1 Step 1: 3-(4-HydroxyphenyI)-8-methoxy-2-(trifluoromethyI)-4H-pyrimido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Method 1, Step 1 with the following modification: Step 1 wras performed with 3-bromo-8-methoxy-2-(trifluoromethyl)pyrimido[l,2-a]pyrimidin-4-one (2.0 g, 6.2 mmol. Intermediate 1-0), (4-hydroxyphenyDboronic acid (1.0 g, 7.4 mmol, Combi-Blocks Inc.). LC / MS (ESI+) m / z = 338.1 ^M-Hi. ]HNMR (400 MHz, DMSO-d6) 5 9.60 (s, 1H), 9.01 (d, 1=7.7 Hz, 1H), 7.18 -7.00 (m, 3H), 6.83 - 6.78 (m, 2H), 4.10 (s, 3H). Intermediate 3-C 8-Bromo-2~(trifluoromethyl)"4H-pyrido[l,2~a]pyrimidin-4-one Step 4 Step 1: 8-Bromo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. The ti tie compound was prepared using the procedure described for Intermediate 1-A, Step 1 with the following modification: Step 1 was performed with 4-bromopyridin-2-amine (Combi-Blocks Inc.). LC / MS (ESC) m / z = 294.2 [M+Hp. }H NMR (400 MHz, DMSO-d6) 5 8.88 (d, 1=7.6 Hz, 1H), 8.26 (d, 1=2.2 Hz, 1H), 7.66 (dd, 1=7.6, 2.1 Hz, 1H), 6.89 (s, 1H). Intermediate 3-D 8~CydopropyI-3~iodo-2-(trifluoromethyI)-4H~pyrido[l,2~a]pyrimidm-4~one intermediate 3~! 8-Bromo-3-iodo-2-(trifluoromethyl)pyrido[l ,2-a]pyrimidin~4-one (150 mg, 0.36 5 mmol, Intermediate 3-1), Pd(PPli3)4 (41 mg, 0.04 mmol), cyclopropylboronic acid (61 mg, 0.72 mmol, Fluorochem) and potassium carbonate (100 mg, 0.72 mmol) were suspended in toluene (3 mL). The reaction mixture was heated to 100°C for 24h. The reaction mixture was concentrated under reduced pressure and the crude residue was purified by silica gel chromatography (eluent: 0-30% EtOAc / cyclohexane) to give 8-cyc1opropyl-3-iodo-2- 10 (trifluoromethyl)pyrido| 1,2-a]pyrimidin-4-one (70 mg,0.18 mmol, 51% yield) as a yellow' solid. LC / MS (ESI+) m / z - 381.1 [M+H]2 1H NMR (400 MHz, CDCh) 3 0.98 - 1.10 (m, 2H) 1.30 - 1.41 (m, 2H) 2.01 - 2.16 (m, 1H) 7.00 - 7.08 (d, 1H) 7.43 - 7.51 (s, 1H) 8.96 - 9.04 (d, 1H). Intermediate 3-E 15 8-(Azetidin-l-yi)-3-iodo-2-(trifluoromethyI)-4H-pyrido[l,2-ajpyrimidin-4-oiie intermediate 3-1 A resealable vial was charged with 8-bromo-3-iodo-2-(trifluoromethyl)pyrido[l,2-a]pyrimidin-4-one (100 mg, 0.24 mmol, Intermediate 3-1), azetidine hydrochloride (25 nig, 0,26 mmol) copper(I)iodide (11 mg, 0.06 mmol), potassium carbonate (40 mg, 0.29 mmol) 20 and DMF (3 mL). Hie reaction mixture was heated to 80°C for Ih. The reaction mixture was diluted with EtOAc and washed with saturated aqueous NH4CI and brine. The organic - 120 - phase was dried and concentrated in vacuo. The crude residue was purified by silica gel chromatography (eluent: 70% EtOAc / cyclohexane) to give 8-(azetidin-l-yl)-3-iodo-2-(trifluoromethyl)pyrido[ 1,2-a]pyrimidin-4-one (48 mg 0.12 mmol, 51% yield) as a pale yellow solid. LC / MS (ESI+) m / z - 396.1 [M+H]\ TlNMR (400 MHz, CDC13) 5 2.45 - 2.71 5    (m, 2H) 4.06 - 4.42 (br s, 4H) 6.28 - 6.39 (d, 1H) 6.39 - 6.57 (dd, 1H) 8.80 - 8.97 (d, 1H). Intermediate 3-F Methyl 4-oxo-3-(l-(2,2,3,3,3-pentafhioropropyI)-lH-pyrazoI-4-yI)-2-(trifluoromethyI)- 4H-pyrido[l,2-a]pyrimidine~8-carboxyIate Intermediate 1-D 10 Step 1: Methyl 4-oxo-3-(l-(2,2,3,3,3-pentafluoropropyl)-lH-pyrazoL4-y!)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxyIate. The title compound was prepared using the procedure described for Method 1, Step 1 with the following modification: Step 1 was performed with methyl 3-iodo-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidine-8-carboxyiate (0.47 g, 1.2 mmol, 15 Intermediate 1-D), 1-(2,2,3,3,3-pentafluoropropy 1)-4-(4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl)-lH-pyrazoIe (0.50 g, 1.54 mmol, Intermediate 2-G). LC / MS (ESr) m / z = 471.1 |M • Hi . lHNMR(400 MHz, CDCfi) 6 9.11 (d, 1=7.5 Hz, 1H), 8.46 (s, 1H), 7.98 (s, 1H), 7.91 (s, 1H), 7.74 (dd, J 7.6. 1.8 Hz, 1H), 4.85 (t, 1=13.9 Hz, 2H), 4.06 (s, 3H). Intermediate 3-G 8-(EthyIthio)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyI)-4H-pyrido[l,2- a] pyrimidin-4-one Pd2{dba)3! SPbos Cs2CO3, dioxane Step 3 Step 1: 8-(Ethylthio)-2-(trifluoromethyl)-4H-pyrido[l.,2-a]pyrimidin-4-one. Sodium ethanethiolate (3,0 g, 36 mmol) was added to a solution of 8-bromo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (3.0 g, 12 mmol, Intermediate 3-C) and in water (45 mL) at room temperature. The reaction mixture was heated to 100°C for 48h. The reaction mixture was cooled to rt and partitioned between water (200 mL) and EtOAc (500 mL), Tire combmed organic layers were washed with brine (250 mL) and dried over sodium sulfate. The filtrate concentrated under reduced pressure to get crude material was purified by silica gel chromatography (eluent: 0-25% ethyl acetate / hexane) to obtain 8-(ethylthio)~2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4~one (0.4 g, 1.46 mmol, 12% yield). LC / MS (ESI +) m / z = 275.0 [M+H]+. !HNMR (400 MHz, DMSO-ds) 5 8.81 (d, J=7.6 Hz, 1H), 7.55 (d, 1=2.1 Hz, 1H), 7.36 (dd, 1=7,6, 2,1 Hz, 1H), 6.69 (s, 1H), 3,26 (t, J=7.4 Hz, 2H), 1.35 (t, 1=7.3 Hz, 3H), 1.29 -- 1.20 (m, IH). Step 2: 8-(Ethy!thio)-3-iodo-2-(trifluoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2. with the following modification: Steps 2. was performed with 8-(ethylthio)-2-(trifluoromethyl)-4H~pyrido[l,2~a]pyrimidin-4-one. LC / MS (ESI +) m / z = 401.1 [M+HJ+. - 122 - NMR (400 MHz, DMSO-ds) 8 8.80 (dd, J 7.6. 2.0 Hz, 1H), 7.53 (t, J 2.2 Hz, 1H), 7.41 (dt, J 7.6. 2.2 Hz, 1H), 3.27 (qt, J 7.5. 2.4 Hz, 2H), 1.35 (td, J 7.3. 2.0 Hz, 3H). Step 3: 8-(Ethylthio)-3-(4-(2,2,24rifluoroethoxy)phenyi)-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Method 1, Step 1 with the following modification: Step 1 was performed with 8-(ethylthio)-3-iodo-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one (0.4 g, 1.0 mmol) and (4-(2,2,2-trifluoroethoxy)phenyi)boronic acid (0.29 g, 1.3 mmol, Combi-Blocks Inc.). LC / MS (ESI +) m / z = 449.0 [M+lp. ‘H NMR (400 MHz, DMSO-d6) 5 8.77 (dd, J=7.5, 1.2 Hz, 1H), 7.57 -7.51 (m, 1H), 7.38 - 7.32 (m, 1H), 7.26 (d, 1=8.4 Hz, 2H), 7.15 - 7.09 (m, 2H), 4.82 (q, J=8.9 Hz, 2H), 3.29 - 3.24 (m, 2H), 1.36 (td, 1=7.3, 1.2 Hz, 3H). Intermediate 3-H 4~Oxo~3-(4-(2,2,2-trifluoroethoxy)phenyI)-2~(trifluoromethyl)-4H-pyrido[l,2~ a] pyrimidine-8-carbaIdehyde Example 1-36                                    intermediate 3-H Step 1: 4-Oxo-3-(4-(2,2,2-trifluoroethoxy)phenyI)-2-(trifluoromethyI)-4H-pyrido[1,2-a] pyrimidine-8-carbaldehyde. A solution of DIBAL-H (IM in DCM, 4 mL, 4 mmol) was added dropwise to a solution of methyl 4-oxo-3-[4~(2.,2,2-trifluoroethoxy)phenyl]-2~(trifluorometbyl)pyrido[l,2-a]pyrimidme-8-carboxylate (1.5 g, 3.36 mmol, Example 1-36) in dichloromethane (30 mL) at -40°C. Stirring was continued for 5 min, followed by addition of aq. IN HC1 (20 mL). Th< reaction mixture was extracted with dichloromethane (2 x 100 mL). Ilie combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[l,2- a]pyrimidine-8-carbaldehyde (0.85 g, 1.3 mmol, 40% yield). The product was used without further purification. LC / MS (ESI +) m / z:=: 417.1 Intermediate 3-1 8-Bromo-3~iodo-2-(trifteoromethyI)-4H~pyrido[l,2-a]pyrimidin-4-one Intermediate 3-C Step 1: 8-Bromo-3~iodo-2-(trifhwromethyI)-4H~pyrido[l,2-a]pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1 B, Step 2 with the following modification: Step 2 w'as performed with 8-bromo-2-(trifhioromethyl)pyrido[l,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 419.0 [M+H]+. 10 Intermediate 3-J 8-Hydroxy-2-(trifliioromethy!)-3-(l-(3,3,3-trifluoropropyI)-lH-pyrazoI-4-yl)-4H- pyrido[l,2-ajpyrimidm-4-one Example 1-S9 Step 1: §~I-Iydroxy-2-(trifluoromethyl)-3-(l-(3,3,3-trifluoropropyI)-lH-pyrazoL4~yI)-4II-15 pyrido[l,2-ajpyrimidin-4-one. Ilie title compound was prepared using the procedure described for Method 10, Step 1 with the following modification: Step 1 was performed with 8-methoxy-2-(tTifluoromethyl)-3-[l-(3,3,3-trifluoropropyl)pyrazol-4-yl]pyrido[l,2-a]pyrimidin-4-one - 124 - (Example 1-69). LC / MS (ESC) m / z - 393.2 [M+H]L iHNMR(400 MHz, DMSO-d6) 3 2.82 - 3.01 (m, 2H) 4.37 - 4.51 (t, 2H) 6.87 - 6.96 (s, 1H) 7.02 - 7.16 (d, 1H) 7.46 - 7.58 (s, 1H) 7.89 - 7.96 (s, 1H) 8.85 - 8.98 (d, 1H) 12.19 - 12.29 (s, 1H). Intermediate 3-K 9-FIuoro-3-iodo-8-methoxy-2-(trifluoromethyI)-4H-pyrido[l,2-ajpyrimidin-4-one NiS MeCN Step 3 Step 1: 3-Fluoro-4-methoxypyridin-2-amine. A mixture of 2-bromo-3-fluoro-4-methoxypyridine (400 mg, 1.94 mmol), L-proline (224 mg, 1.94 mmol), sodium azide (190 mg, 2.91 mmol) and copper (I) oxide (306 mg, 2.14 10 mmol) in DMSO (6 mL) was stirred for lOh at 100°C. Hie mixture was filtered and the filtrate was directly purified by flash chromatography (Cl8 cartridge, NH3 0.1% in water: ACN as eluant, from 100% aqueous solution to 8:2) to obtain 3-fluoro-4-methoxypyridin~2-amine as a white solid (185 mg, 1.302 mmol, 67% yield). LC / MS (ESF) m / z = 143.1 [M+H]L 15 Step 2: 9-FIuoro-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a}pyrimidin-4-one. The title compound was prepared using the procedure described for Intermediate 1-A, Step 1 with the following modification: Step 1 was performed with 3-fluoro-4-methoxypyridin-2-amine. LC / MS (EST) m / z ::: 263.3 [M+H]1. - 125 - Step 3: 9-FIuoro-3riodo-8-methoxy-2-(trifluoromethyi)-4H-pyrido[l,2-a|pynmidm-4-one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Step 2 was performed with 9-fluoro-8-methoxy-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidm-4-one. LC / MS (ESI+) m / z ===388.9 Intermediate 3-L 3-Bromo-7-fIuoro-8-methoxy-2-(trifluoromethyl)-4H- pyrido[l,2-a]pyrimidin-4-one i) LDA,THF, trimethylborate, ii) H2O2, AcOH Step 1 Mel Ag2CO3 oaaaaaaaaaaaanjgg^ DCM Step 2 Pd9(dba)3, Xanthphos ~ K3PO4 1,4-dioxane Step 3 H TFA -----Ss DCM Step 4 O O Step 5 0 NBS MeCN Step 6 O F F 10 Step 1: 2-chioro-5-fluoropyridin-4-ol. To a solution of 2-chloro-5-fiuoropyridine (11,6 mL, 114 mmol) in THF (120 mL) at -78°C Lithium diisopropylamide (2M in THF, 65 mL, 130 mmol) was added dropwise. The mixture w as allowed to warm up at -60° over 3h then the reaction was cooled to -78°C and trimethyl borate (25.4 mL, 228 mmol) was slowly added. The temperature was slowly increased to 0°C and the mixture was stirred for 2h. Acetic acid (19.6 mL, 342 mmol) was added at the same temperature followed by dropwise addition of hydrogen peroxide (30% in water, 29 mL, 285 mmol) after 20 minutes. The reaction mixture was wanned to r.t. and then stirred overnight. Saturated sodium thiosulfate aqueous solution was added to reaction and the mixture was extracted with EtOAc (x2) and DCM (x2). Hie aqueous phase was acidified with HCL 6M solution to pH 5 / 6 and further extracted with EtOAc (x2) and DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated under vacuum. The resulting crude was triturated in DCM and the solid was collected to give 2-chioro-5-fluoropyridin-4-ol as a white solid (15.53 g, 105.3 mmol, 92% yield). LC / MS (EST) m / z = 148.1 / 150.1 AM H . Step 2: 2-chloro-5-fIuoro-4-methoxypyridine. To 2-chloro-5-fluoropyridin-4-ol (15.53 g, 105.3 mmol) in DCM (300 mL) was added silver carbonate (62.4 g, 224.64 mmol) and iodomethane (6.99 mL, 112.32 mmol) and the mixture was stirred at r.t. overnight. The mixture was filtered and the residue washed with water (x2). Tire organics phase was dried over magnesium sulfate and the solvent removed under vacuum. The residue was then purified by flash column chromatography (S1O2, Cy:EtOAc as eluant, from 100% Cy to 7:3) to give 2-chloro-5-fluoro-4-methoxypyridine as a white solid (5.36 g, 33.2 mmol, 32,5% yield). LC / MS (ESP) m / z = 161.9 / 163.9 AM H • Step 3: 2-chloro-5-fluoro-4-methoxypyridine. A mixture of 2-chloro-5-fluoro-4-methoxypyridine (5.36 g), carbamic acid tert-butyl ester (4.43 g, 37.8 mmol) and potassium triphosphate (10.17 g, 47.24 mmol) in 1,4-dioxane (200 mL) was degassed for 15 minutes, then Pdzdbaj (2.88 g, 3.15 mmol) and (5-diphenylphosphino-9,9-dimethyl-4-xanthenyl)“diphenylphosphine (3.64 g, 6.3 mmol) were added and tire mixture was stirred at 100°C for 15 h. Ilie mixture was filtered and the residue concentrated under vacuum. The resulting material was purified by flash chromatography (SijO, Cy:EtOAc as eluant, from 100% cy to 7:3) to obtain impure tert-butyl N-(5-fluoro-4-methoxypyridin-2-yI)carbamate which was used directly in the following reaction. LC / MS TM m / z == 187.3 [M-tBu+H]L Step 4: 5-fluoro~4-methoxypyridin-2-amine. To crude tert-butyl N-(5-fluoro-4-methoxypyridin-2-yl)carbamate (8.3 g) in DCM (70 mL) was added trifluoroacetic acid (10 mL) and the mixture was stirred at r.t. overnight. The mixture was concentrated and the residue loaded into an SCX cartridge, washed with - 127 - DCM and MeCN and eluted with 10% ammonia in MeCN. The solvent was evaporated to obtain 5-fluoro-4-medioxypyridin-2-amine as apale orange solid (2.16 g, 15.2. mmol). LC / MS (ESL) m / z = 143.1 | M • Hi . Step 5: 7-fluoro-8-methoxy-2-(trifIuoromethyl)pyrido^l,2-a]pyrimidin-4-one. A mixture of 5-fluoro-4-methoxypyridm-2-amme (2.16 g) 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (10.33 mL, 70.67 mmol) and bismuth trichloride (0.45 g, 1.41 mmol) was stirred at 120°C for 24 hours. The mixture was partioned between EtOAc and water and the organic phase was dried over Na2SO4, filtered and concentrated under vacuum. Ilie resulting crude material was purified by flash chromatography (SiCh, DCM: MeOH as eluant, from 100% DCM to 95:5) followed by reverse phase flash chromatography (Cl 8, 0.1% HCOOH solution in water: acetonitrile, from 100% aqueous solution to 1:1) to obtain 7-fluoro-8-meihoxy-2-(trifluoromethyl)pyrido[l,2-a]pyrimidin-4-one as a white solid (1.94 g, 7.41 mmol, 52% yield). LC / MS (ESC) m / z - 263.1 [M+H]+. Step 6: 3-bromo~7-fluoro-8~methoxy~2~(trifluoromethyI)-4H-pyrido[l,2~a]pyrimidin-4-one. A mixture ofN-bromosuccinimide (1.45 g, 8.16 mmol) and 7-fluoro-8~methoxy~2-(trif]uoromethyl)pyrido[l,2-a.]pyrimidin-4-one (1..94 g, 7.41 mmol) in MeCN (15 mL) was stirred at 80°C for Ih. The mixture was partioned between EtOAc and water and the organic phase was washed with sat. sol. NaHCOs and sat. sol. NaiSCE. Then the organic phase was dried over Na^SOa, filtered and concentrated under vacuum. The crude material was purified by flash chromatography (SiCE, Cy:EtOAc as eluant, from 100% cy to 7:3) to obtain 3-bromo-7-fluoro-8-methoxy-2-(trifluoromcthy1)-4H-pyrido[l ,2-a]pyrimidin-4-one as a white solid (2.53 g, 7.40 mmol, quantitive yield). LC / MS (ESI+) m / z = 341.1 / 343.1 [M+H]+. Intermediate 3-M 3-Bromo~8-methoxy-2-(trifIuoromethyI)-4H~pyrimido[l,2-b]pyridazin-4~one H2N Step 1: terfibutyl N-(5-methoxypyridazin-3-yl)carbamate. A solution of 3-chloro-5-methoxypyridazine (250 mg, 1.73 mmol, Combi-Blocks Inc.), carbamic acid tert-butyl ester (263 mg, 2.25 mmol) and cesium carbonate (794 mg, 2.42 mmol) in 1,4-dioxane (5 mL) was degassed with a flow of nitrogen for 10 minutes then (5-diphenylphosphino-9,9-dimethyl-4-xanthenyl)-dipheny1phosphine (150 mg, 0,260 mmol) and palladium(II) diacetate (27 mg, 0.12 mmol) were added. The mixture was heated at 100 °C for 22 hours. The mixture was filtered, diluted with EtOAc and washed with brine twice. The organic phase was dried, filtered and concentrated under vacuum. The resulting material was purified by flash chromatography (SiO?, Cy: EtOAc as eluant, from 100% Cy to 50:50) to give tert-butyl N-(5-methoxypyridazin-3-yl)carbamate as a white solid (160 mg, 0,710 mmol, 41% yield). LC / MS (ESH) m / z = 226.2 [M+H]+. >HNMR (400 MHz, CDC13) 5 8.86 (d, J 2.6Hz. H fi. 8.59 (d, J-2.7Hz, IH), 7.75 (d, J 2.71Iz. H B. 7.66 (s, H h. 6.96 (d, J==2.6Hz, IH), 3.96 (s, IH), 3.95 (s, 3H), 1.56 (s, 9H). Step 2: 5-methoxypyridazin-3-amine. Trifluoroacetic acid (1.07 mL, 14.03 mmol) was added to a solution of tert-butyl N-(5-methoxypyridazin-3-yl)carbamate (158 mg, 0.700 mmol) in DCM (4 mL) at 0°C. The mixture was stirred at room temperature for 3 hours. The mixture was concentrated to give a - 129 - crude material that was purified by SCX cartridge to obtain 5-methoxypyridazin-3-amine as a white solid. (60 mg, 0.480 mmol 68% yield). LC / MS (ESH) m / z - 126.2 [M+H] \ 'HNMR (400 MHz, DMSO-dH 3 8 17 (d, 1 2.6Hz. 1H), 6.22 (d. 1 2.7Hz. 3H), 378 (s, 3H). Step 3: 8-methoxy-2-(trifIuoromethyI)-4H-pyrimido[l,2-b]pyridazin-4-one. A mixture of 5mrethoxypyridazm~3-amme (85 mg, 0,68 mmol), 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (1.0 mL, 6.79 mmol) and bismuth trichloride (21 mg, 0.07 mmol) was stirred at 120°C for 24 h. The mixture was diluted with water and extracted with EtOAc twice. The organic phase was dried over Na2SO4, filtered and concentrated under vacuum to give a crude material that was purified by flash chromatography (SiO?, Cy:EtOAc as eluant, from 80:20 to 100% EtOAc) to obtain 8-methoxy-2-(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one as a pale yellow' solid (80 mg, 0.33 mmol, 48% yield). LC / MS (ESI / ) m / z == 246.1 | M H1 . NMR (400 MHz, DMSO-d6) 8 8.80 (d, J 2.9Hz. IH), 7.58 (d, J 2 ^Hz. IH), 6.83 (s, IH), 4.05 (s, 3H) Step 4: 3-bromo-8-methoxy-2-(trifluoromethyI)-4H-pyrimido[l,2-b]pyridaziii-4-one. A mixture of 8miethoxy-2-(trifluoromethyi)pyrimido[l,2"b]pyridazin-4"One (95 mg, 0.390mmol) and 14momopyrrolidine-2,5-dione (103 mg, 0.58 mmol) in MeCN (3 mL) was stirred at room temperature for 18 hours and at 80°C for 1 hour. The mixture was concentrated, dissolved in DCM and washed subsequently with saturated aqueous NaiSiOs and NaHCOj solutions and brine. The organic phase was dried and concentrated to give 3-bromo-8-methoxy~2-(trifluoromethyl)-4H-pyrimido[l,2-b]pyridazin-4-one as a yellow solid (112 mg, 0.346 mmol, 89% yield). LC / MS (ESH) m / z = 324.0 / 326.0 [M+H] \ Tl NMR (400 MHz, DMSO-ds) 8 8.87 (d, J =2.8Hz, IH), 7.61 (d, J 2.8Hz. IH), 4.06 (s, 3H). Intermediate 3-N 34odo~2-(trifhioromethyI)-4H-pyrido[l,2-a]pyriniidin-4-one To a suspension of potassium (chloromethyl)trifluoroborate (156 mg, 1 mmol) in methanol (4 mL) was added sodium methoxide (52 mg, 0.95 mmol) and mixture was stirred at 70°C for 4 h then the solvent evaporated. The resulting crude material was redissolved in 1,4-dioxane (4 mL) and water (1 mL), then cesium carbonate (157 mg, 0,48 mmol), 8-bromo-3-iodo-2-(trifluoromethyl)pyrido[l,2-a]pyrimidin-4-one (Intermediate 3-1, 100 mg, 0.24 mmol) and palladium triphenylphosphine (28 mg, 0.02 mmol) were added and mixture was stirred at 90°C overnight. After cooling mixture was diluted with EtOAc and washed with water. The organic phase was dried and evaporated and crude was purified by flash chromathography (SiO?, Cy / EtOAc 50:50) affording 3-iodo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one as a yellow solid (62 mg, 0.182 mmol, 77% yield). LC / MS (EST ) m / z = 431.0 [M+H]L Intermediate 3-0 3-Bromo~7-methoxy-2-(trifIuoromethyl)-4H~pyrido|l,2-a]pyrimidin-4-one Step 1: 7-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. A mixture of 5-methoxypyridin-2-amine (1.0 g, 8.06 mmol, Fluorochem Ltd), 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (2.36 mL, 16.1 mmol) and polyphosphoric acid (19.3 g, 80.55 mmol) was stirred at 120°C for 20 h then allowed to cool. The mixture was carefully added to NaHCO? aq sat sol (80 mL) at 0°C and pH adjusted to 7. Then the aqueous phase was extracted with AcOEt (3 x 100 mL). Tire organic phase was dried over NazSO^ filtered and concentrated under vacuum to give a crude material that was purified by flash chromatography (SiO2, Cy:EtOAc from 90:10 to 80:20) to obtain 7-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one as a pale yellow solid (1.66 g, 6.78 mmol, 84% yield). - 131 - LC / MS (ESI4) m / z - 254.2 j M I H . rH NAIR (400 MHz, CDCh) 8 3.89 - 4.07 (s, 3H) 6.80 (s, 1H) 7.67 (dd, 1H) 7.78 (d, 1H) 8.62 (d, 1H). Step 2: 3-bromo-7-methoxy-2-(trifluoromethyI)-4H-pyrido[l,2-ajpyrimidin-4-oiie. A mixture of obtain 7-methoxy-2-(trifluoromethyl)-4H-pyrido[l,,2-a]pyrimidin-4-one (400 mg, 1.64 mmol) and N-bromosuccinimide (321 mg, 1.8 mmol) in MeCN (10 mL) was stirred at room temperature for 5 hours. Tire mixture was concentrated, dissolved in DCM and washed subsequently with saturated aqueous Na2S2O3 and NaHCOs solutions and brine. Ilie organic phase was dried and the crude was purified by column chromatography (SKh, Cy:EtOAcfrom 9:1 to 6:4) to obtain 3-bromo-7-methoxy-2.-(trifluoromethyl)-4H-pyrido[],2-a]pyrimidin-4-one as a white solid (466 mg, 1.44 mmol, 88% yield). LC / MS (ESI4) m / z = 323.1 / 325.1 [M+H]4. !HNMR (400 MHz, CDCh) 8 4.02 (s, 3H) 7.70 (dd, 1H) 7.80 (d, 1H) 8.61 (d, J 1H). Intermediate 3-P 3-Bromo~8-(2-hydroxypropan-2-yl)-2-(triflu0romethyl)-4H~pyrido[l,2-a]pyrimidin-4-one Step 1: 8-(2-hydroxypropan-2-yl)-2-(trifluoromethy0-4H-pyrido[l,2-a]pyrimidin-4-one. A mixture of 2-(2-aminopyridm-4-yl)propan-2-ol (828 mg, 5.44 mmol, Combi-Blocks Inc), 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (3.98 mL, 27.2 mmol) and bismuth trichloride (172 mg, 0.54 mmol) was stirred at 120°C for 24 hours, lire mixture was diluted with water and extracted with EtOAc twice. The organic phase was dried over NajSCL, filtered and concentrated under vacuum to give a crude material that was purified by flash chromatography (SiO2, Cy:EtOAc as eluant, from 80:20 to 100% EtOAc) to obtain 8-(2-hydroxypropan-2-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (284 mg, 1.04 mmol, 19% yield). LC / MS (ESI4) m / z = 273.1 [M+H]L - 132 - Step 2: 3-bromo-8-(2-hydroxypropan-2-yi)-2-(trifluoromethyl)-4H-pyrido[l,2-a] pyriniidin-4-one. A mixture of 8-(2-hydroxypropan-2-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (284 mg, 1,04 mmol) and N-bromosuccinimide (204 mg, 1.15 mmol) in MeCN (5 mL) was stirred at room temperature for 5 hours. The mixture was concentrated, dissolved in DCM and washed subsequently with saturated aqueous NaiSiCh and NaHCOj solutions and brine. The organic phase was dried and concentrated to give 3-bromo-8-(2-hydroxypropan-2-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one as a yellow solid (335 mg, ¢).95 mmol, 91%yiekl). LC / MS (ESR) m / z - 381.1 / 383.1 iM • H| . 4 i AMR (400 MHz, DMSO-dft) 8 1.51 (s, 6H) 5.66 (s, 1H) 7.67 - 7.78 (m, 1H) 7.80 - 7.90 (m, 1H) 8.91 - 9.08 (m, 1H) Intermediate 3-Q 3-Bromo-7-chIoro-2-(trifiuoromethyl)-4H-pyrido[l,2-aJpyrimidiii-4-one Step 1: 7~chloro-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. A mixture of 2-amino-5-chIoropyridine (1250 mg, 9.72 mmol), 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (2.84 mL, 19.5 mmol) and bismuth trichloride (153 mg, 0.49 mmol) was heated at 120°C for 18 hours. MeOH was added and the precipitate was filtered under vacuum to obtain 7-chloro-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one as a pale yellow solid (753 mg, 3.03 mmol, 31% yield). LC / MS (ESM m / z = 249.1 / 251.1 |M Hi . 'H NMR(400 MHz, DMS()-d6) 5 9.04 (d, J 2.3Hz. 1H), 8.20 (dd, 1==9.5, 2.4Hz, 1H), 7.92 (dd, 1==9.5, 0.7Hz, 1H), 6.93 (s, 1H). Step 2: 3-bromo-7-cHoro-2-(trifluoromethyi)-4H-pyrido[l,2-a|pyrimidm-4-one. A mixture of 7-chloro-2-(trifluoromethyi)-4H-pyrido[l,2-a]pyrimidin-4-one (753 mg, 3 mmol) and N-bromosuccinimide (800 mg, 4.5 mmol) in MeCN (20 ml.) was stirred at - 133 - 80°C for 6 hours. The mixture was concentrated, dissolved in DCM and washed subsequently with saturated aqueous ^282()3 and NaHCOs solutions and brine. Ilie organic phase was dried and concentrated to give 3-bromo-7-cbloro-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one as a yellow solid (989 mg, 3.02 mmol, quantitative yield). LC / MS (ESI+) m / z - 327.0 / 329.0    1 i | . '11 NMR (400 MHz, DMSO-d J 5 7.96 (d, J 9.46 Hz, 1H) 8.23 (dd, J 9 46. 2.20 Hz, 1H) 9.00 - 9.12 (m, 1H). Intermediate 3-R 3-Bromo-8-(methoxymethyl)-2-(trifluoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one Step 1: 8-(methoxymethyl)-2-(trifluoromethyI)-4H~pyrido[l,2-a]pyrimidin-4-one. A suspension of 4-(methoxymethyl)pyridin-2-amine (100 mg, 0.72 mmol, Enamine Ltd), bismuth(III) chloride (23 mg, 0.07 mmol) and 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (0.53 mL, 3.62 mmol) was stirred at 120°C for 48 h. After cooling mixture was diluted with EtOAc and washed with water. The organic phase was dried and evaporated, and crude was purified by flash chromatography (SiO?, Cy / EtOAc 1:1) affording 8-(methoxymethyl)-2-(Mfluoromethyl)-4H-pyridojT,2-a]pyrimidin-4-one (70 mg, 0.27 mmol, 37% yield). JH NMR (400 MHz, CDCi ) 5 9.07 (d, 1H), 7.79 (dq, 1H), 7.26 (dd, 1H), 6.78 (s, 1H), 4.62 (d, 2H), 3.53 (s, 3H). Step 2: 3-bronm-8-(methoxymethyI)~2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm~4-one. 8-(methoxymethyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one (70 mg, 0.27 mmol) in MeCN (3 mL) was added N-bromosuccinimide (53 mg, 0.30 mmol) and mixture was stirred at RT for 3h. The mixture was concentrated, diluted with EtOAc and washed subsequently with ^282()3 and NaHCOs. The organics were combined, dried and evaporated, affording 3~Lmomo-8-(methoxymethyl)-2~(trifluoromethyl)-4H-pyrido[l,2- - 134 - a]pyrimidin-4-one as yellow solid (84 mg, 0.25 mmol, 92% yield). LC / MS (ESI+) m / z = 327.0 / 329.0 i M H | [HNMR (400 MHz, CDCh) 8 9.09 (dd, 1H), 7.82 (dq, 1H), 7.32 (dd, 1H), 4.62 (d, 2H), 3.54 (s, 3H). The Intermediates 3-S to 3-AF in Table 2 were prepared analogous to preparation 5 of Intermediate 3-R. Table 2 Int# Chemical Structure Name Starting Reagents and Conditions LC / MS (ESF) m / z 3-S । O JI JI Rr Xs X? X. ! F F 3-bromo-8-methoxy-6-methyl-2-(trifluoromethyl) -4H-pyrido[l,2-a]pyrimidin-4-one 4-methoxy-6-methylpyridin-2-amine (preparation described in patent application WO2014 / 153280) 337.1 / 339.1 [M+HT 3-T z 0 W z Tt / .......\ TJ 3 -bromo-4-oxo- 2-(trifluoromethyi) -4H-pyrido[l,2-a]pyrimidine-7-carbomtrile 6-amino-3-py ri dinecarbomtril 318.1 / 320.1 iMHi 3-U 0 N rr LL X / F F 3-bromo-7-methoxy-2-(trifl uoromethyl) -4H- ' pyrimido|l,2~ b]pyridazin-4-one 6-methoxypyridazin-3-amine (preparation described in patent application WO2013 / 6845 8) 324.1 / 326.1 [M Hi 3-V O      0 \ A   JL _Br I           f Cs.     JC / N f^f methyl 3-bromo-4-oxo-2- (tri fluoromethyl) -4H-pyrido[L2-a]pyrimidme-7-carboxylate 6-amino-3-pyridinecarboxylic acid methyl ester 351.2 / 353.2 [M Hi 3-X a N L L JL F F F 3-bromo-7-methyl-2-(trifluoromethyl) -4H-pyrido[L2-a]pyrimidin-4- one 2-amino-5-methylpyridine 307.1 / 309.1 Al Hi 3-Y 0 A    JL ^Br I 1 IL F F F 3-bromo-7-fluoro-2-(tri fluoromethyl) -4H-pyrido[L2-a]pyrimidin-4-one 2-amino-5-fluoropyridine 311.0 / 313.0 iM Hi 3-Z 0 JL .Br N IT I            F K    IL / N 7C f F 3-bromo-7-methyl-2-(trifluoromethyl) -4H-pyrimido[l,2-b]pyridazin-4-one 3-amino-6-methyipyri d azine (Apollo Scientific Ltd) 308.0 / 310.0 [M+H]+ 3-AA 0 o^^Jl 1 / zL F F 3-brom o-2-(trifluoromethyl) -4H,6H,7H,9H-pyrimido|2,l-c][l,4]oxazin-4-one morpholin-3-ylideneamine hydrochloride (preparation described in patent application WO2003 / 93279) 299.0 / 301.0 A1lli 3-AB 0 JL. n V 1 f 0 F F r 3-bromo-8-methyl-2-(trifluoromethyl) -4H- ’ pyrimido[l,2-b]pyridazin-4-one 3-amino-5-methylpyridazine (Apollo Scientific Ltd.) 307.9 / 309.9 Ai IH 3-AC / O JO JH \ y IF \ Y^q "75 / ......A / Xi "» Tt 3-bromo-7-fluoro-8-methoxy-2-(trifl uoromethyl) -4H- ' [l,3]diazino[l,2-a]pyrimidin-4- one prepared from 2-chloro-5-fluoro-4-metboxypyrimidin e (Apollo Scientific Ltd) as described for Intermediate 3-M 341.9 / 343.9 Ai Hi 3-AD a JL.Br L. X 1 F F F 3-bromo-7,8-dimethyl-2-(trifluoromethyl) -4H- “ pyrimido[l,2~ b]pyridazm-4-one 5,6-dim ethylpyridazin-3-amine (Enamine Ltd) 321.9 / 323.9 Al Hi 3-AE 5.. U- / \   / u. O^ / $5 o 3-bromo-7-chloro-8-methyl- (trifl uoromethyl) -4H~pyrido[l,2-a]pyrimidin-4-one 2-amino-5 -chloro- 4-picoline (Combi-Blocks Inc.) 340.9 / 342.9 Al Hi 3-AF w o J....... "H 3-bromo-7- fluoro-8~methyl“ 2-     ’ (trill uoromethyl) -4H-pyrido[l,2-a]pyrimidm-4~ one 2-Amino-5 -fluoro- 4-picoline (Combi-Blocks Inc) 325.0 / 327.0 [M+H]+ Intermediate 4-A 3-Bromo-8-methoxy-2-(trifluoromethyI)-4H-[l,3]diazino[l,6-aJpyrimidiii-4-one NaH trifluoracetic anhydride NH2 DMF Step 1 O Step 1: 2,2,2~trifluoro~N~(6-methoxypyrimidin~4-yl)acetamide. 5 6-methoxy-4-pyrimidinamine (2.0 g, 15.98 mmol) was dissolved in DMF (106 mL) and sodium hydride (60% in oil, 1.28 g, 31.97 mmol) was added at room temperature. After Ih, trifluoroacetic anhydride (5.37 g, 25.57 mmol) was added and the mixture was left to react at room temperature for 30 min. The reaction mixture was poured into cold water and extracted with EtOAc. The organic phase was washed with water, brine, dried over NazSCh and evaporated in vacuo. Hie crude was purified by flash chromatography (SiCh, eluted with cyclohexanes:EtOAc 100:0 to 75:25) to afford 2,2,2-trifluoro-N-(6-methoxypyrimidin-4-yl)acetamide (2.08 g, 9.41 mmol, 59% yield). LC / MS (ESC) m / z == 222.3 | M • i H . ;H NMR (400 MHz, DMSO-d6) 8 3.95 (s, 3H) 7.36 (s, 1H) 8.69 (s, 1H) 12.38 (br s, 1H). Step 2: Ethyl 4,4,4-trifluoro-3-K6-methoxypyrimidin-4-yi)amino|but-2-enoate. 2,2,2-trifluoro-N-(6-methoxypyrimidin-4-yl)acetamide (2.08 g, 9.41 mmol) was dissolved in toluene (23 mL). (Carbethoxymethylene)triphenylphosphorane (6.55 g, 18.81 mmol) was added and the reaction was left to react at room temperature for 2h then at 5 5 °C for 3 h. The solvent was removed in vacuo and the crude was purified by flash chromatography (SiOz, eluted with cyclohexane:EtOAc 100:0 to 80:20) to give ethyl 4,4,4-trifluoro-3-[(6-methoxypyrimidin-4-yl)amino]but-2-enoate (671 mg, 2.30 mmol, 24.5% yield). LC / MS (EST) m / z = 292.3 iM H| . TlNMR (400 MHz, DMSO-ds) 8 1.03 (t, 3H) 3.87 (s, 3H) 3.95 (q, 2H) 6.16 (s, 1H) 6.25 (d, 1H) 8.30 (d, 1H) 9.55 (br s, 1H). Step 3: 8-methoxy~2-(trif!uoromethyI)-4H-[l,3]diazjno[l,6-a]pyrimidin-4-one. Ethyl 4,4,4-trifluoro-3-|(6-methoxypyrimidin-4-yl)amino]but-2-enoate (671 mg, 2.30 mmol) was repeatedly evaporated at 60°C from a mixture of water (70 mL) and MeCN (40 mL). The crude was purified by flash chromatography (SiO?„ eluent cyclohexanes: EtOAc 100:0 to 55:45) to afford 8-methoxy-2-(trifluoromethyl)-4H-[l,3]diazino[l,6-a]pyrimidin-4-one (300 mg, 1.22 mmol, 53% yield). LC / MS (EST) m / z == 246.3 [M+H]+. Step 4: 3-bromo-8-methoxy-2-(trifluoromethyI)-4H-[l,3]diazino[l,6-a]pyrimidin~4-one. A mixture of afford 8-methoxy-2-(trifluoromethyl)-4H-[l,3]diazino| l,6-a]pyrimidin-4-one (300 mg, 1.22 mmol) and N-bromosuccinimide (240 mg, 1.35 mmol) in MeCN (9.5 mL) was stirred at room temperature for 5 hours. The mixture was concentrated, dissolved in EtOAc and washed subsequently with saturated aqueous NaaSaOs and NaHCO? solutions and brine. The organic phase was dried and concentrated to give the crude that was purified by flash chromatography (SiO2, eluant from cyclohexane:EtOAc 100:0 to 50:50) to give 3-bromo-8- - 138 - methoxy-2-(trifluoromethyl)-4H-[l,3]diazino[l,6-a]pyrimidin-4-one as a yellow solid (153 mg, 0.47 mmol, 39% yield). LC / MS (ESP) m / z = 324.2 / 326.2 [M+H]+. lH NMR (400 MHz, DMSO-d6) 3 4.07 (s, 3H) 7.13 (m,lH) 9.57 - 9.64 (m, 1H). 5           Intermediates 4-B to 4-1 of Table 3 were prepared analogous to preparation of Intermediate 4-A. Table 3 Inf # Chemical Structure Name Starting Reagents and Conditions LC / MS (ESI+) m / z 4-B O L L JI F F F 3-bromo-7- methoxy-2-(trifluoromefhyl)- 4H- ” [l,3]diazino[l,2-a]pyrimidin-4-one 2-amino-5-methoxypyrimidi ne 324.0 / 326.0 |M Hi 4-C 0 1 Jk 11 F F F 3-brom o-2~ (tri fl u orom etb y 1) -4H-pyrazino[l,2“ a]pyrimidin-4-one 2-aminopyrazine 294.0 / 296.0 |M Hi 4-D O Jl^Br N If p F 3-bromo-7~methyl-2-(trifluoromethyl)-4H-pyrazino[l,2-a]pyrimidin-4-one 2-amino-5-methylpyrazine (Apollo Scientific Ltd) 308.1 / 310.1 [M+HT 4-E O °qy_____9 o “TS / ......V X, / X “= Ti 3 -bromo-7 -chloro-2-(trifluoromethyl)-4H-pyrazino [1,2-a]pyrimidin-4-one 2-amino-5-chloropyrazine (Combi-Blocks Inc.) 328.0 / 330.0 |M-Hi 4-F 0 N Ac F F 3-bromo-7-methoxy-2-(trifl u orom eth y 1) -4H-pyrazino[l,2-a]pyrimidin-4-one 2-ammo-5-methoxypyrazme (Fluorochem Ltd.) 323.9 / 325.9 Hl 4-G 0 L A JU F F 3 -bromo-7 -methyl -2-(trifluorome thy i) -4H-[I,3]diazino[l,2-a]pyrimidin-4-one 2-amino-5-methyipyrimi dine (Fluorochem Ltd.): note: Step 3 - Heated to 225°C in diphenyl ether 307.9 / 309.9 |M Hl 4-H 0 A LA jo 1 A 3-bromo-9-metbyl- 2- (tri fluo romethyl) - 4H-pyrazino[l,2-a]pyrimidin-4-one 2-amino-3-methylpyrazine (Fluorochem Ltd) 308.0 / 310.0 |XL 111 4-1 0 JL .Br LI JL J 1          F F 3-bromo-7,9-dimethyl-2-(tri fluoromethyl)-4H-pyrazino [ 1,2-a]pyrimidin-4-one 2-amino-3,5-dimethylpyrazine (Combi-Blocks Inc) 322.0 / 324.0 [M+H] + Intermediate 4-J 3-Bromo~7-£ydopropyL2~(trifhwrometlliyll)-4I-I-pyrido[l,2-a]pyrimidin~4-one MeCN Step 3 - 140 - Step 1: 7-bromo-2-(trifluoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one. A mixture of 5-bromo-2-pyridinamine (1250 mg, 7.23 mmol), 4,4,4-trifluoro-3-oxobutanoic acid ethyl ester (2.11 mL, 14.5 mmol) and bismuth trichloride (114 mg, 0.36 mmol) was heated at 120°C for 18 hours. Hie reaction was then cooled down to RT, diluted with a mixture of distilled water / brine and extracted with EtOAc. The organic phase was then washed with brine (x2) and concentrated in vacuo. The mixture was purified by flash chromatography (SiOz, EtOAc:Cy from 3:97 to 25:75) followed by reverse phase flash chromatography (Cl 8, HzO + HCOOH 0.1% : MeCN from 97:3 to 40:60) to afford 7-bromo-2-(trifluoromethyl)-4H-pyrido| l,2-a]pyrimidin-4-one as a white solid (517 mg, 1.76 mmol, 24% yield). LC / MS (ESF) m / z - 293.0 / 295.0 [M+H]+. Step 2: 7-CyclopropyI-2-(trifluoromethy!)-4H-pyrido[l,2-a]pyrimidin-4-one. A mixture of 7-bromo-2~(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (150 mg, 0.51 mmol), palladium triphenylphosphine (592 mg, 0.51 mmol), cyclop ropy Iboronic acid (44 mg, 0.51 mmol) and potassium carbonate (71 mg, 0.51 mmol) was suspended in dry toluene (3 mL) and in a sealable vial. It was degassed with several vacuum / nitrogen cycles and then it was shaken and heated to 100°C for 18h. The mixture was cooled to RT, diluted with EtOAc and washed with distilled water and with brine. The organic phase was dried over NazSCh and concentrated in vacuo. The mixture was then purified by flash chromatography (SiOz, EtOAc:Cy from 3:97 to 30:70) to afford 7-cyclopropy1-2-(Mfluoromethyl)-4H-pyridojT,2-a]pyrimidin-4-one as awhile solid. (110 mg, 0.43 mmol, 85% yield). LC / MS (ESF) m / z - 255.1 [M+H]4. Step 3: 3-bromo-7-cydopropyI-2-(trifluoromethyi)-4H-pyrido[l,2-a]pyrimidin-4-one. A mixture of 7-cyclopropyl“2-(trifluoromethyl)pyrido[l,2-a]pyrimidin-4“One (110 mg, 0.43 mmol) and N-bromosuccinimide (85 mg, 0.48 mmol) in MeCN (3 mL) was stirred at room temperature for 1.5 hours. Tire mixture was diluted with DCM and washed subsequently with saturated aqueous NazSzOs and brine. The mixture was purified by flash chromatography (SiOz EtOAc:Cy from 3:97 to 25:75) to afford 3-bronio-7-cyclopropyl-2-(trifluoromethyl)-4H-pyrido[l,2~a]pyrimidin-4-one as a white solid (130 mg, 0.39 mmol, 90% yield). LC / MS (ESF) m / z = 333.1 / 335.1 [M+H]’. Intermediate 4-K 7-(Azetidin-l-yl)-3-bromo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one azetidine Pd(OAc)2 Xantphos Cs2CO3 1,4-dioxane Step 1 Step 1: 7-(azetidin-l-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. 5           A screw-capped vial was charged with 7-bromo-2-(trifluoromethyl)-4H-pyrido[l,2- a]pyrimidin-4-one (Intermediate 4-J, Step 1, 60 mg, 0.20 mmol), 1,4-dioxane (3 ml), cesium carbonate (67 mg, 0,20 mmol), azetidine (0.02 mL, 0.25 mmol), (5-diphenylphosphino-9,9-dimethyl-4-xanthenyl)-diphenylphosphine (12 mg, 0.02 mmol), and palladium(II)diacetate (2.3 mg, 0.010 mmol). The mixture was stirred at 100°C in a screw-10 capped vial for 4h then cooled down to rt, diluted with a mixture of water and brine and extracted with EtOAc. The organic phase was dried and evaporated, and the crude was purified by flash chromatography (SiOz,Cy:EtOAc from 95:5 to 60:40) followed by reverse phase flash chromatography (C18, H2O + 0.1% HCOOH:MeCN from 97:3 to 50:50) to give 7“(azetidin“l-yl)-2-(trifluoromethyl)pyrido[l,2-a]pyrimidin~4-one as a yellow solid (35 mg, 15   0.13 mmol, 63% yield). LC / MS (EST) m / z = 270.1 [M+H]4. Step 2: 7-(azetidin-l-yl)-3-bromo-2-(trifluoromethyl)-4H-pyrido[l,2-ajpyrimidin-4-one. A mixture of 7-(azetidin-l-yl)-2.-(trifluoromethyl)-4H~pyrido[l,2~a]pyrimidm-4-one (35 mg, 0.130 mmol) and N-bromosuccinimide (25 mg, 0.140 mmol) in MeCN (2.5 mL) was stirred at room temperature overnight. The mixture was concentrated in vacuo, diluted with EtOAc 20 and washed subsequently with saturated aqueous Na2S20j and NaHCOs. The organic phase was dried and concentrated in vacuo. The mixture was purified with by reverse phase chromatography (Cl 8, H2O + HCOOH 0.1% : MeCN from 97:3 to 50:50) to obtain 7-(azetidin-l-yl)-3-bromo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one as a yellow solid (18 mg, 0.052 mmol, 40% yield). LC / MS (ESI ) m / z === 348.0 / 350.0 f H . Intermediate 4-L 3-Bromo~7-(methoxymethyI)-2~(trifIuoromethyi)-4II-pyrido[l,2-a]pyrimidin-4-one Step 1: 7-(bromomethyl)-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one. 5            A suspension of 7-methyl-2-(trifluoromethyl)pyrido[l,2-a]pyrimidin~4-one (Intermediate 3-X, Step 1, 500 mg, 2.19 mmol), N-bromosuccinimide (585 nig, 3.29 mmol) and 2,2''-azobis(2-methylpropiomtrile) (36 mg, 0.220 mmol) in carbon tetrachloride (10 mL) was stirred at 80°C for 7h. The mixture was evaporated and crude was purified by flash chromatography (SiO2, Cy / EtOAc from 100:0 to 70:30) to give 7-(bromomethyl)-2- 10 (trifluoromethyl)-4H-pyrido[L2-a]pyrimidm-4~one (130 mg, 0.423 mmol, 19% yield). LC / MS (ESL) m / z = 307.0 / 309.0 [M+H]L Step 2: 7-(methoxymethyI)-2-(trifiuoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. To a suspension of 7-(bromomethyl)-2-(trifluoromethyl)-4H-pyrido[ l,2-a]pyrimidin-4-one (60 mg, 0.20 mmol) in methanol (4 mL) was added sodium methoxide (11.6 mg, 0.2.1 15 mmol) and the mixture was stirred at rt for 3 days. The mixture was evaporated and crude was purified by flash chromatography (SiCL, Cy / EtOAc from 100:0 to 70:30) affording 7-(methoxymethyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one as a white solid (34 mg, 0.132 mmol, 67% yield). LC / MS (ESI+) m / z = 2.59.1 [M+H]+. - 143 - Step 3: 3-bromo-7-(methoxymethy!)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one. To a solution of 7-(methoxymethyl)~2.-(trifliioromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (34 mg, 0.13 mmol) in MeCN (3 mL) was added N-bromosuccinimide (26 mg, 0.14 mmol) and mixture was stirred at rt for 18h. Tire mixture was concentrated, diluted with EtOAc and washed with NaNiO; and NaHCOs. Ilie organic phases were combined, dried and evaporated affording -bromo-7~(methoxymethyl)-2-(trifluoromethyl)-4H~pyrido[l ,2-a]pyrimidin-4~one (35 mg, 0.104 mmol, 79% yield). LC / MS (ESI+) m / z = 337.0 / 339.0 Hi . Intermediate 4-M 3-Bromo-7-[(djmethy!amjno)methyI]-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4- one Step 1: 3-bromo-7-[(dimethylamino)methylj-2-(trifluoromethyO-4H-pyrido[l,2-a] pyriniidin-4-one. A solution of 3 -bromo-7-methyl-2-(trifluoromethyl.MH-pyndo [ 1,2-a]pyrimidin-4-one (Intermediate 3-X, 30 mg, 0.090 mmol), N-bromosuccinimide (16 mg, 0.090 mmol) and 2,2'-azobis(2-methylpropionitrile) (1.5 mg, 0.010 mmol) in MeCN (3 mL) was shaken at rt for 2h then warmed to 80°C and shaken at that temperature for 24h. The mixture was evaporated and crude was purified by flash chromatography (SKh, Cy / EtOAc from 100:0 to 70:30) affording 3-bromo-7-(bromomethyl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one as pale yellow solid (15.5 mg, 0.040 mmol, 46% yield). LC / MS (ESI+) m / z = 387.1[M+H]+. - 144 - Step 2: 3-bromo-74(dimethyIamino)methyi]-2-(trifluoromet:hyl)-4H-pyrido[l,2-a] pyrimidin-4-one. To a solution of 3-bromo-7-(bromomethyl)-2-(trifluoromethyl)~4H-pyrido[l ,2-a]pyrimidin-4-one (15 mg, 0.040 mmol) in MeCN (1 mL) was added dimethylamine (2 M in MeOH, 0.05 mL, 0.100 mmol) and the mixture was stirred at rt for Ih. The mixture was evaporated affording crude 3-bromo-7-[(dimethylamino)methyl]-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one which was used directly in the next step. LC / MS (EST) m / z = 350.2 / 352.2 [M+11|. Intermediate 4-N 8-Methoxy-3-(4,4,5,5-tetramethyl-l,3,2-dioxaboroIan-2-yI)-2-(trifluoromethyi)-4H- pyrido [1,2-a] pyrim idin-4-one B2pm2, K2CO3, Pd(ppoa2~oc^ CF3 Toluene Step 1: 8-methoxy~3-(4,4,5,5-tetramethyl-l,3,2-dioxaboroIan-2-yI)-2-(trifluoromethyl)-4H-pyrido JI ,2- a] pyrimidin-4-one. 3-Bromo-8-metiroxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (Intermediate 1-A, 0,5 g, 1.55 mmol), bis(pinacolato)diboron (0.51 g, 2.01 mmol), potassium acetate (0.41 g, 4.18 mmol) and [1,1’-bis(diphenylphosphino)ferrocene]dichloropalladium (II) DCM complex (63.4 mg, 0.08 mmol) were combined in a microwave vial in toluene (10.0 mL), and degassed for 10 minutes. The tube was sealed and the reaction stirred at 130°C for 3 hours under microwave irradiation. After this time, the mixture was diluted with EtOAc, washed with water, dried and eliminated. The residue was purified by flash chromatography (SiOz, cyclohexane: EtOAc) to give 8-methoxy-3-(4,4,5,5 -tetramethyl-1,3,2-di oxaborolan-2 -yI)-2 -(trifluoromethyl)-4H~pyrido[l,2-a]pyrimidm-4-one (30 mg, 0.08 mmol, 5% yield). LC / MS (ESL) m / z = 371.4 [M+H|+. Intermediate 4-0 3-Br om o-2-eth oxy-8-m ethoxypy rido [1,2-a] py rim idin-4-one todoethane Step 2 NBS, MeCN Step3 XO‘ Step 1: 2-hydroxy-8-methoxypyrido[l ,2-a]pyrimidin-4-one. 4-Methoxy-2-pyridinamine (3.0 g, 24.17 mmol) was dissolved in dry' DCM (30 mL) and the solution was cooled to 0° C. Propanedioyl chloride (2.82 mL, 29.0 mmol) was added dropwise under nitrogen atmosphere and the reaction was allowed to stir at room temperature for 48 hours. After this time, the reaction was filtered, washed with DCM, the organic phase dried and evaporated. The crude material was used as such in the following reaction. Step 2: 2-ethoxy-8-methoxypyrido[l,2-ajpyrimidin-4-one. The crude 2~hydroxy~8-methoxypyrido[l,2-a.]pyrimidin-4-one obtained from Step 1, was suspended in DMF (3.0 mL), and cesium carbonate (373 mg, 1.14 mmol) was added. The mixture was degassed and stirred at room temperature for 10 minutes. lodoethane (0.09 mL, 1.09 mmol) was added, the reaction was stirred at 65° C overnight. Water was added and the mixture extracted with EtOAc. Tire organic phase was dried and eliminated. Tire obtained crude was purified by flash chromatography (SiCL, cyclohexane:EtOAc) to afford 2-ethoxy"8-methoxypyrido[l,2-a]pyrimidin-4-one (102. mg, 0.46 mmol, 44% yield). LC / MS (ESL) m / z 22% [M+H|+. Step 3: 3-bromo-2-ethoxy-8-methoxypyrido[l,2-a]pyrimidin-4-oiie. 2~Ethoxy-8-methoxypyrido[l,2~a]pyrimidin~4-one (102 mg, 0.46 mmol) was dissolved in MeCN (5.0 mL). N-bromosuccinimide (86.6 mg, 0.49 mmol) was added and the - 146 - mixture was stirred at room temperature overnight. After this time, the solvent was eliminated and tire crude was purified by flash chromatography (SiOi, cyclohexane :EtOAc) to afford 3-bromo~2-ethoxy-8-methoxypyrido[l,2-a]pyrimidin-4-one (44.0 mg, 0.15 mmol, 31 % yield). LC / MS (ESP) m / z - 301.0 / 302.0 [M+H]t Intermediate 4-P 3-Bromo-l-(2,2,3,3,3-pentafluoropropyl)-l,2,4-triazole Br Cs2CO3, M®CN 3-Bromo-lH-l,2,4-tnazole (500.0 mg, 3.38 mmol), 2,2,3,3,3-pentafluoropropyltriflate (953.3 mg, 3.38 mmol) and cesium carbonate (1.10 g, 3.38 mmol) were suspended in MeCN (20 mL) and stirred at 60°C for 2 hours. Tire mixture was concentrated under vacuum, EtOAc was added and the organic phase was washed with water. The solvent was removed to give the product 3-bromo-1-(2,2,3,3,3-pentafluoropropyl)-l,2,4-triazole (865 mg, 3.09 mmol, 91%yield). lH NMR(500 MHz, DMSO-ds) 5 5.41 (t, J=15.23 Hz, 2H), 8.75 (s, IH). Intermediate 4-Q [2-(2,2,2-Trifluoroethoxy)pyrimidm-5-yIjboronic acid bis(pinacolato)diboron 2,2,2-tnfluoroethanol Step 1 F F Pd(dppf)Ci2.DCM KOAc 1,4-dioxane Step 2 Step 1: 5-bromo-2-(2,2,2-trifluoroethoxy)pyrimidine. To a solution of 2,2,2-trifluoroethanol (0.78 g, 7.75 mmol) in DMF (10 mL) at 0cC 60% sodium hydride (0.31 g, 7.75 mmol) was added. The mixture was left to reach r.t. in 15 minutes then 5-bromo-2-chloropyrimidine (1.0 g, 5.17 mmol) was added. The mixture was stirred at room temperature for 2 hr. EtOAc and brine were added, phases were separated, organic one was dried over NazSOa, filtered and concentrated. The obtained crude was purified by flash-chromatography (SiCh, Cy / EtOAc 95 / 5) to give 5-bromo-2-(2,2,2-trifluoroethoxy [pyrimidine as a colourless oil. (893 mg, 3.47 mmol, 67% yield). LC / MS (EST) m / z == 257.1 / 259.1 |XM Hh Step 2: [2-(2,2,2-trifluoroethoxy)pyrimidm-5-yI]boronic acid. To a solution of 5-bromo-2-(2,2,2-trifluoroethoxy)pyrimidine (0.89 g, 3.46 mmol) in L4-dioxane (10 mL) 4,4,5,5~tetramethyl~2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (1.32 g, 5.19 mmol), potassium acetate (1030 mg, 10.39 mmol) and [ l,T-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloride, complex with dichloromethane (142 mg, 0.170 mmol) were added. The mixture was degassed for 10 minutes then it was stirred at 90°C for 3 hr. It was concentrated and purified by flashchromatography (C18, H2O+0.1%HCOOH / CH3CN from 1:0 to 1:1) to give [2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]boronic acid as a white solid (514 mg, 2.32 mmol, 67% yield). rH NMR (400 MHz, DMSO-d6) 8 4.97 - 5.00 (m, 1H) 5.06 (q, 1==8.95 Hz, 2H) 8.52 (s, 2H) 8.89 (s, 2H). Intermediate 4-R [2-(2,2,3A3-PentaflMoropropoxy)pyrimidin-5-y!]boronic acid 2,2,3,3,3- pentefluoropropanoi Step 1 bis(pmaco!ato)diboron Pd(dppf)C!2.DCM N । F KOAc          f 'If 1,4-asoxane B s F F The titie compound was prepared using the procedure described for Intermediate 4- Q, Steps 1 and 2 with the following modification: Step 1 was performed with 2,2,3,3,3-pentafluoropropan-l-ol. Step 1 LC / MS (ESI+) m / z ==307.1 / 309.1 [M+H]’'. Step 2 LC / MS (ESP) m / z = 273.1 [M+H]’, !H NMR (400 MHz, DMSO-d6) 8 5.16 (t, 1=13.20 Hz, 2H) 8.47 - 8.55 (m, 2H) 8.89 (s, 211). Intermediate 4-S Potassium trifluoro-[l-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]boranuide Step 1: Potassium trifluoro-|l-(2,2,3,3,3-pentafluoropropyI)pyrazol-4-yl]boranuide. 5            A mixture of 1-(2.2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetrametiiyl-l,3,2- dioxaborolan-2-yl)pyrazole (Intermediate 2-G, 1.0 g, 3.07 mmol) and potassium bifluoride (0.79 g, 10.12 mmol) in acetone (15 mL) and water (5 mL) was stirred at room temperature for 2h. The solvent was evaporated, the residue suspended in hot acetone (25 mL) and filtered to remove undissolved salts. The solvent was evaporated, residue redisssolved in hot 10 acetone cooled to rt and allowed to stand overnight. The crystallised product was collected, washed with cold acetone and dried under vacuum to give potassium trifluoro-[ 1-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]boranuide (270 mg, 0.88 mmol, 29% yield). rH NMR (400 MHz, DMSO~d&) 8 4.98 (t, J 15.30 Hz, 2H), 7.03 - 7.33 (m, 2H). Intermediate 4-T 15 l-[(2,2-Dif!uorocydopropyl)methyl]-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)pyr azole - 149 - Step 1: 1-((2,2-difluorocyclopropyI)methyl(-4-(4,4,5,5-tetram ethyl-1,3,2-dioxaborolan-2-yDpyr azole. A resealable vial was charged with 4-pyrazoleboronic acid pinacol ester (1 g, 5.15 mmol), potassium carbonate (1.42 g, 10.3 mmol), acetonitrile (20 ml), and 2-(bromomethyl)-1,1-difluorocyclopropane (1.06 g, 6.18 mmol). The reaction mixture was heated at 80°C for 4h, then cooled to rt and filtered, washing with MeCN. The filtrate was concentrated under reduced pressure and purified by flash chromatography (SiOz, 0-50% EtOAc / cyclohexane) to afford l-[(2,2-difluorocyclopropyl)methyl]-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrazole (460 mg, 1.62 mmol, 31% yield) as colorless oil. LC / MS (ESI+) m / z = 285.2 [M Hi;. Intermediate 4-U l-(Cydopropyhnethyl)-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrazole Step 1: l-(cyclopropylmethyi)-4-(4,4,5,5-tetramethyl-l,3,2-dioxaboroIan-2-yl)pyrazoIe. Cyclopropanemethanol (0.89 g, 12.37 mmol) was added dropwise to a stirred solution of 4-pyrazoleboronic acid pinacol ester (2.0 g, 10,31 mmol), triphenylphosphine (2.7 g, 10.31 mmol) and DIAD (2.0 mL, 10.31 mmol) in THF (30 mL) under nitrogen atmosphere at 0°C. The reaction mixture was allowed to warm to rt and stirred for 24h. The mixture was concentrated under reduced pressure, cyclohexane was added and the resulting precipitate was filtered off. The filtrate was evaporated and the crude was purified by flash chromatography (SiOz, 0-50% EtOAc / cyclohexane) affording l-(cyclopropylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole as a white solid (1.78 g, 7.17 mmol, 70% yield). LC / MS (ESE) m / z - 249.1 iM H| . Intermediate 4-V l-[(3,3~DifluorocydobutyI)methyH-4-(4,4,5,5-tetramethyI-l,3,2-dioxaboroIan~2-yl)pyr azole 5 Step 1: l-[(3y3-difluorocydobutyl)methyl]-4~(4,4,5,5-tetramethybl,3ll2-dioxaborolan-2-y!)pyr azole. A solution of 3-(bromomethyl)-l,l-difluorocyciobutane (195 mg, 1.05 mmol) in DMF (0.6 mL) was added to a stirred suspension of 4-pyrazoleboronic acid pinacol ester (200 mg, 1.03 mmol) and cesium carbonate (537 mg, 1.65 mmol) in DMF (1.4 ml) at 0°C. 10 Hie reaction mixture was stirred at rt for 18h, then filtered, washing with EtOAc. The filtrate was w ashed with brine (2x), dried over Na?SO4, filtered and concentrated under reduced pressure to afford 1-((3,3-difluorocyclobutyl)methyl]-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan~2“yl)pyrazole as a colorless oil. (270 mg, 0.9 mmol, 88% yield). LC / MS (ESI ') m / z = 299.1 |M ■ Hi 15 Intermediate 4-W 4,4,5,5-Tetramethyl-2-[4-(2,2,2-trifluoroethoxy)phenyl]-l,3,2-dioxaborolane - 151 - Step 1: l-bromo-4-(2,2,2-trifluoroethoxy)benzene. 4-methylbenzenesulfonic acid 2,2,2-trifluoroethyl ester (14.7 g, 57.9 mmol) was added to a stirred mixture of 4-bromophenol (10 g, 57.8 mmol) and potassium carbonate (39.9 g, 289 mmol) in DMF (80 ml) at 0°C. The reaction mixture was heated at 110°C for 16h. After cooling to rt, the mixture was partitioned between water and EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. Purification by flash chromatography (SiO?, 50% EtOAc / cyclohexane) afforded 1 -bromo-4-(2,2,2-trifluoroethoxy)benzene (10.9 g, 42.73 mmol, 74% yield). 'HNMR (400 MHz, DMSO-de) 5 4.78 (q, >8.88 Hz, 2H), 7.02 - 7.08 (rn, 2H), 7.48 - 7.56 (m, 2H). Step 2: 4,4A5-tetramethyl-2-[4-(2,2,2-trifluoroethoxy)phenyl]-l,3>2-dioxaborolane. A mixture of l-bromo-4-(2,2,2-trifluoroethoxy)benzene (5.0 g, 19.61 mmol), bis(pinacolato)diboron (5,48 g, 21.57 mmol), potassium acetate (5.77 g, 58.82 mmol) and [l,r-bis(diphenylphospbino)ferrocene]dich]oropalladium(H) (719 mg, 0.98 mmol) in 1,4-dioxane (50 ml) was degassed with nitrogen tor 5 min, then heated at 110°C for 4h. After cooling to rt, the mixture was filtered -with EtOAc through a pad of celite. Ure filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography (S1O2, 0-3% EtOAc / cyclohexane) to give 4,4,5,5-tetramethyl~2“[4-(2,2.,2-tri fluoroethoxy )phenyl]-L 3,2-dioxaborolane (2.76 g, 9.13 mmol, 47% yield) as colorless oil, LC / MS (ESI+) m / z = 303.1 [M+H]2 Intermediate 4-X l-(Oxetan-3-ylmethyl)-4-(4,4^,5-tetramethyH3»2-dioxaboroIan-2-yl)pyrazole dioxane Step 1 - 152 - Step 1: l-(oxetan-3-ylmethy!)-4-(4,4,5,5-tetramethyl-l,3,2-dioxaboroIan-2-yI)pyrazole. A micro wave vial was charged with 4-pyrazoleboronic acid pinacol ester (194 mg, 1 mmol), oxetan-3~ylmethanol (88 mg, 1 mmol), 2-tributylphosphoranylideneacetonitrile (0.52 ml, 2 mmol) and 1,4-dioxane (3 mL). Hie resulting mixture was subjected to microwave irradiation at 150°C for 45 min. After cooling to rt, the mixture was partitioned between water and EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (SiCh, 50-90% EtOAc / cyclohexane) obtaining l-(oxetan-3-ylmethyl)-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrazole (270 mg, 1 mmol, 100% yield) as brown oil. LCZMS (ESP) m / z == 265.0 jM 111 Intermediate 4-Y l-(2,2,3,3,3-PentafIuoropropyl)-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrazole Step 1: 1-(2,2,3,3,3-pentanuoropropyi)-3-(4,4,5,5-tetram ethyl-1, 3,2-dioxaborolan-2-yl)pyr azole. A resealable vial was charged with 3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-IH-pyrazole (1.0 g, 5.15 mmol), sodium carbonate (1.09 g, 10.31 mmol), MeCN (5 mL) and 2,2,3,3,3-pentafluoropropyl tnfluoromethanesulfonate (1.32 mL, 7.99 mmol). Ilie mixture was heated at 80°C for 20 h, then cooled to rt and partitioned between water and EtOAc. The organic phases was dried over Na2SOi, filtered and evaporated under reduced pressure to give l-(2,2,3,3,3-pentafluoropropyl)-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrazole (1 g, 3.07 mmol, 60% yield) which was used in the next reaction without further purification. LC / MS (ESI / ) m / z == 327.2 |M Hi . Intermediate 4-Z 9-Chloro-34odo-8-methoxy-2-(trifluoromethyI)-4H-pyrido[l,2-a]pyrimidin-4-one BL LL Step 1: 9-ChIoro-8-methoxy-2-(trifluoromethyI)-4H-pyrido[l,2~a]pyrimidin-4~one. 5           Hie title compound was prepared using the procedure described for Intermediate 1- A, Step 1 with the following modification: step 1 was performed with 3-chloro~4~ methoxypyndin-2-amine (preparation described in WO2017197555). LC / MS (ESI ') m / z = 279.0 / 281.0 iMHfo Step 2: 9-Chloro-3~iodo-8-methoxy~2-(trifluoroniethyl)-4H-pyrido[l,2-a]pyrimidm~4- 10 one. The title compound was prepared using the procedure described for Intermediate 1B, Step 2 with the following modification: Step 2 was performed with 9-chloro-8-methoxy-2-(trifhioromethyl)-4H-pyrido[l,2-a]pyrimidin-4~one. LC / MS (ESI+) m / z ==404.9 / 406.9 [M Hi. 15 - 154 - Synthesis of Examples: Method 1 Example 1-1: 3-(4-(8-Methoxy-4-oxo-2~(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-3-yl)phenyl)propanenitrile Intermediate 1 -A           Step 1 Step 1: 3-(4-(8-Methoxy-4-oxo-2-(trifluoromethyi)-4H-pyrido[l,2-ajpyrimidin-3-yDphenyOpropanemtrile. A resealable vial with was charged with 3-bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one (Intermediate 1-A, 170 mg, ¢).526 mmol), (4-(2 10 cyanoethyl)phenylboronic acid (138 mg, 0.789 mmol, Combi-Blocks Inc.), tris(dibenzylideneacetone)dipalladium(0) (24 mg, 0.026 mmol), 2-dicyclohexylphosphino-2,6'-dimethoxy-1,T-biphenyl (22 mg, 0.053 mmol), and cesium carbonate (340 mg, 1.1 mmol). The vial was evacuated and backfilled with nitrogen. This procedure was repeated 3 times, followed by the addition of 1,4-dioxane (850 pl). The reaction mixture was heated to 15   90°C and stirred for 12h. The reaction mixture was quenched with water (2 mL) and diluted with EtOAc (2 mL). Tire reaction mixture was filtered through a pad of silica. gel. The organic phase was separated, washed with brine, dried over magnesium sulfate, filtered, and adsorbed onto silica gel. Ilie crude product was purified by silica gel chromatography (eluent: 0-70% EtOAc / heptane) to provide 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H- 20 pyrido[l,2-a]pyrimidin-3-yl)phenyl)propanenitrile as a white solid. LC / MS (EST) m / z = 374.0 [M+H]+. !HNMR (400 MHz, CD2C12) 6 2.70 (t, 1=7.57 Hz, 2H) 3.03 (t, 1=7.46 Hz, 2H) 4.03 (s, 3H) 6.86 - 7.01 (m, 1H) 7.05 (d, J 2.70 Hz, IH) 7.23 - 7.40 (m, 4H) 8.91 (d, J 7Hz, IH). - 155 - Examples 1-2 to 1-88 listed in Table 4 were prepared following the procedure described in Method 1, Step 1, above as follows. Table 4 Ex. Chemical Structure Name Reagent and Method Changes 1-2 n 1 jj i i n f I               F r (4-(8-methoxy-4-oxo-2-(trifluoromethyl) -4H-pyndo[l,2-a]pyrimidin-3-yl)phenyl)acetonit rile (4-(cyanomethy l)phenyl) boronic acid (Combi-Blocks Inc.) 1-3 JI L „n—4 A J, L JI f F F 8-methoxy-3-(l~ phenyl- 1H-pyrazoI-3-yl)-2-(trifluoromethyl) -4H-pyndo[l,2-a]pyrimidm-4-one 1-Phenyl-3-(4,4,5,5-tetram ethyl-1,3,2-di oxaborolan-2-yl)-1H-pyrazole (Essen Scientific) 1-4 u. O c# o= / \ Y. 2S““{ o o— 3-(4-((2,2-difluorocycloprop yl)methoxy)pheny l)-8-methoxy-2-(trifluoromethyl) -4H-pyrido[l,2-a]pyrimidin-4-one 2-(4-((2,2-difluorocyclopropyl)methoxy ]phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Intermediate 2-A) 1-5 €3 n Ji > r^N'^r*0 L L JI f 8-methoxy-3-(3-phenyl-1,2-oxazol-5-yl)-2-(trifluoromethyl)-4H-pyndo[l,2-a]pyrimidm-4-one 3-Phenyl-5-(4,4,5,5-tetram ethyl-1,3,2-dioxaborolan-2-yi) isoxazole (Essen Scientific) 1-6 o .....z^x L L n f T           F F 8-methoxy-3-(2-phenyl-1,3-oxazol-5-yl)-2-(trifluoromethyl) -4H-pyndo[l,2-a]pyrimidin-4-one 2-phenyl~5-(4,4,5,5-tetrara ethyl-1,3,2-dioxaborolan-2-yl)oxazole (Intermediate 2-B) 1-7 g L 1 JI F 1            / F 3-(l-benzofuran-2-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin~4-one 3-iodo-8-methoxy-2-(trifluoroniefhyl)pyrido [1,2-a]pyrimidin-4-one (Intermediate 1-B), benzo [b]furan-2 -boronic acid (Alfa Aesar) 1-8 0 JL L JI f I               F r 3-(4-(cyclopropylmetho xy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyndo[l,2-a]pyrimidm-4-one 3-iodo~8-methoxy-2-(trifluoromethyl)pyrido [ 1,2-a]pyrimidin-4-one (Intermediate 1-B), [4-(cyclopropylm eth oxy)phenyl ] boranediol (Combi-Blocks Inc.) 1-9 F f<Lf p           i 0 KT° AA X / X. |            / F 3-(2-fluoro-4-(trifluoromethoxy) phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin~4-one 2-fluoro-4-triiluoromethoxyphenyiboron ic acid (Combi-Blocks Inc.) 1-10 A o c o V# o ® s 3-(4-(2,2-difluoroethoxy)ph enyi)-8-methoxy- 2- (trifi aoromethyl) -4H-pyrido[l,2-a]pyrimidin~4-one 2-(4-(2,2-difluoroethoxy)phenyl)-4,4,5,5-tetramethyl-l,3,2-d ioxaborolane (Intermedi ate 2-C) 1-11 / o €3 feo Tt^ / .....\ T3 3-(4-(2-fluoroethoxy)phen yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin~4-one 4-(2-fluoroethoxy)phenylboronic acid (Combi-Blocks Inc.) 1-12 £ Q O 1*****^             3iAa oA ,Z 2:- / Q / ° 2-(difluoromethyl) -3-(3-fluoro-4-(2,2,2-trifl uoroethoxy )ph enyi)-8-methoxy-4H-pyrido[l,2-a]pyrimidin-4-one 3-bromo-2-(difluoromethyl)-8-methoxy-pyrido[ 1,2-a]pyrimidin-4-one (Intermediate 1-C); 3-fluoro-4-(2,2,2-trifl uoroethoxy )benzeneboron ic acid (Combi-Blocks Inc.) 1-13 o x.       Jk F 2-(difluoromethy 1) -8-methoxy-3-(6-(2,2,2-tri fluoroethoxy)-3 -pyridinyl)-4H-pyrido[l,2-a]pyrimidin-4-one 3-bromo-2-(difluoromethyl)-8-methoxy-pyrido| 1,2-a]pyrimidin-4-one (Intermediate 1-C); [6(2,2,2-     ' ' tri fluoroetboxy)py ridin -3 -yl] boronic acid (Combi-Blocks Inc.) 1-14 / O C3 to "n~~ / 4 i 2T ~n 2-(difluoromethyl) -8 -m ethoxy-3 -(1(3,3,3-trifluoropropyl)-lH-pyrazol-4-yl)-4H-pyrido[l,2-a]pyrimidm-4-one 3-bromo-2~(difluoromethyl)~ 8-methoxy-pyrido [1,2-a]pyrimidin-4-one (Intermediate 1-C); 4(4,4,5,5 -tetramethyl-1,3,2-dioxaborolan-2-yl)-l-(3,3,3-trifluoropropyl)pyrazole (Intermediate 2-D) 1-15 o "■V      J<S> Jt. „F F (difluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)ph enyl)-4H-pyrido[l,2-a]pyrimidin-4-one 3-bromo-2-(difluoromethyl)-8-methoxy-pyrido [1,2-a]pyrimidin-4-one (Intermediate 1-C); 4-(2,2,2-trifluoroethoxy)benzeneboron ic acid (Combi-Blocks Inc.) 1-16 / O <3 z tsO -51 o Tl 2- (difhi orom ethyl) -8-methoxy-3-(l-(4,4,4-trifluorobutyl)-lH-pyrazol-4-yl)- 4H-pyrido[L2-a]pyrimidin-4-one 3-bromo-2-(difluoromethyl)-8-methoxy-pyrido[ 1,2-a]pyrimidin-4-one (Intermediate 1-C); 4(4,4,5,5 -tetramethyl-1,3,2-dioxaborolan-2-yl)-l-(4,4,4-trifl u orobutyl)-1 H-pyrazoJ e (Intermediate 2-E) 1-17 o fS’K / “X ji           #“F JL jk JI F 1               F F 3-(1-(4-fluorophenyl)- 1H-pyrazol-4-yl)-8-methoxy-2-(tri fluorome thy I) -4H-pyrido[L2-a]pyrimi din-4-one [ 1 -(4-fluorophenyl) -1 h-pyrazol-4-yl]boronic acid (Combi-Blocks Inc.) 1-18 F 0        / =K L 1 JI F 1                F F 3-(1-(3-fluorophenyl) -1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one 1-(3 -fluorophenyl)- Ih-pyrazole-4-boronic acid pinacol ester (Combiphos Catalysts.) 1-19 F rvv \sA f 0 sfN u i            f Ax. .As 2L / O^KX,. 1                F F 8-methoxy~2-(trifluoromethyl)-3-(1-(3- ' ' (trifluoromethyl)p henyl)-lH-pyrazol-4-yl)-4H-pyrido[l,2-a] pyrimidm-4-one (l-[3- (trifluoromethyl)phenyl] -1 h-pyrazol-4-yl)boronic acid (Combi-Blocks Inc.) 1-20 \f R zZSx. AX AC 1YT f L L JI f 1                 F F 3-(2-fluoro-4-(2,2,2-trifi no roe thoxy)ph enyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a] pyrimidin-4-one 2-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyi)~ 4,4,5,5-tetramethyl-l,3,2~ dioxaborolane (Intermediate 2-F) 1-21 sr F 0 f»Ny / ~CFS n Ln--A •’yWZ 0          F F 4-oxo~3-(l- (2,2,3,3,3-pentafluoropropyl) -lH-pyrazol-4-yl)-2-(trifl uoromethyl)-4H-pyrido[l,2-a]pyrimidme-8-carboxylic acid methyl 3-iodo-4-oxo-2-(triflnoromethyl) -4H-pyrido[ 1,2-a]pyriniidine-8-carboxylate (Intermediate 1-D); 1-(2,2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetramethy 1 -1,3,2 -dioxaborolan-2-yl)- 1H-pyrazole (Intermediate 2-G) 1-22 p F S^F L L JI F I               F F 8-(dimethvlamino)-3-(1-(2,2,3,3,3-pentafluoropropyl) -1 H-pyrazol-4-yl)-” 2-      ” (trifluoromethyl)-4H-pyrido[l,2-a] pyrimidin-4-one 8-(dimethyl amino)-3-iodo-2-(trifluoromethyl)-4H-pyrido[l ,2-a] pyrimidin-4-one (Intermediate 1-E), Intermediate 2-G 1-23 ,, EX Z-2X O' u. O ZT / 8-(methylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl) -lH-pyrazol-4-yl)-2- (trifl uoromethyl)-4H-pyrido[l,2-a] pyrimidin -4-one 3-iodo-8-(methylamino)-2-(trifluoromethyl)-4H-pyrido[l ,2-a] pyrimidin-4-one (Intermediate 1-F), Intermediate 2-G 1-24 0 r^N'^Sr^ L. 1 H f F F 3-(4-(8-rnethoxy-4-OXO-2-(tri fluorome thy I) -4H-pyrido[l,2-a]pyrimidin-3-yl)-IH-pyrazol-l-yl)propanenitrile 3-(4-(4,4propanenitrile,5,5-tetram ethyl -1,3,2-dioxaborolan-2-yl)- 1H-pyrazol-l-yl) (Intermediate 2-H) 1-25 Or c l|                 j JU JC / 1               F F 8-acetyl-3-(4-(2,2,2-trifl uo roe thoxy)ph enyi)-2-(tri fluorome thy I) -4H-pyrido[l,2-a]pyrimidin-4-one 8-acetyl-3-iodo-2- (trifluoromethyl) -4H-pyrido[l ,2-a]pyrimidin-4-one (Intermediate 1-G); (4(2,2,2-trifluoroethoxy)phenyi)boroni c acid (Combi-Blocks Inc.) 1-26 ,N O   fffN / / .. JL       N“^ 1? L L JI f F F (4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm~3 -yl) -IH-pyrazol-l-yl)acetonitriie 2-(4-(4,4,5,5 -tetramethyi-l,3,2-dioxaborolan-2-yi)-1H-pyrazol-l-yl) acetonitrile (Intermediate 2-1) 1-27 F, / 0  F5^ X^-F X O St— / pF f L L JI f p F 4-oxo-3-(l- (2,2,3,3,3-pentafluoropropyi) -lH-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrmudine-8-carbonitrile 3-iodo-4-oxo-2- (trifluoromethyl)-4H-pyrido[l,2-a]pyrirmdine-8-carbonitrile (Intermediate 1H), Intermediate 2-G 1-28 / —z: s: >=o / A o T3 ' TJ 8-(dimethyiamino)-3-(4-(2,2,2- ' trifluoroethoxy)ph enyi)-2- (tri fluorome thy I) - 8-(dimethylamino)~3-iodo~2-(trifluoromethyl) -4H-pyrido[l ,2-a]pyrimidin-4-one (Intermediate 1-E), (4-(2,2,2-    ' trifluoroethoxy )phenyl)boroni c acid (Combi-Blocks Inc.) 4H-pyrido[l,2-a]pvrimidin-4-one 1-29 o \..... V# zx / 8-(niethylamino)-3-(4-(2,2,2- ' trifluoroethoxy )ph enyD-2- (trifluoromethyl)-4H-pyrido[l,2-a]pyrimidm-4-one 3-iodo-8-(methylamino)-2-(trifluoromethyI)-4H-pyrido [ 1,2 -a] pyrimi din-4-one (Intermediate 1-F), (4(2,2,2-trifluoroethoxy )pheny l)boroni c acid (Combi-Blocks Inc.) 1-30 0     X^F y L n—' p" JL JL JI F F F 8-(methylsulfanyl)-3-(1-(2,2,3,33-pentafluoropropyl) -1 H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a] pyrimidin-4-one 3-iodo-8~(methylthio)-2-(trifluoromethyl)-4H-pyrido [ 1,2 -a] pyrimi din-4-one (Intermediate 1-K); Intermediate 2-G 1-31 a XY n jl JL jl f H           F / V-(4-oxo-3-(4-(2,2,2-trifl uoroe thoxy)ph enyl)-2-(tri fluorome thy I) -4H-pyrido[L2-a]pyrimidin-8-yl)acetamide N-(3-iodo-4-oxo-2- (trifl uorom ethyl) -4H-pyrido[l ,2-a]pyrimidin~8-yl)aeetamide (Intermediate '     1-L), (4-(23,2- trifl uoroethoxy)phenyl)boroni c acid (Combi-Blocks Inc.) 1-32 L F 9 ry f L L Ji f 1               F F 8-(2-propanyl)-3-(4-(2,2,2-trifluoroethoxy)ph enyl)-2- (tri fluorome thy I) -4H-pyrido[L2-a]pyrimidin-4-one 3-iodo-8-isopropyl-2-(trifluoromethyl) -4H-py rido [ 13-a]pyrimidin-4-one (Intermediate 1-M), (4(2,2,2-        ’ trifluoroethoxy )phenyl)boroni c acid (Combi-Blocks Inc.) 1-33 o o o o z >sO o \-~l "H ii « w % o “0 v> 8 -(methyl oxy-ds )3-(1-(2,2,33,3-pentafluoropropyl) - lH-pyrazol-4-yl)-7_ (tri fluorome thy I) -4H-pyrido[l,2-a.]pyrimidin-4-one 3-bromo-8-(methoxy-d3)-2-(trifl uorom ethyl) -4H-pyrido[ 1,2-a]pyrimidin-4-one (Intermediate 1-N), Intermediate 2-G 1-34 F, FF _ 8 XXXz 1                F F 8-methoxy-3-(l-(2,2,3,3,3-' pen tafluoropropyl) - lH-pyrazol-4-yl)- 3 -B romo-8-methoxy-2~ (trifluoromethyl)-4H-pyrimido 11,2-a]pyrimidin~4- 2-(trifluoromethyl)-4H-pyrimido [1,2-a]pyrimidin-4-one one (Intermediate 1-0), Intermediate 2-G 1-35 . V o L L JI f 1               F F 8-(niethylsulfanyl)-3-(4-(2,2,2- ’ trifl uoroe thoxy)ph enyl)-2-(trifluoromethyi)-4H-pyrido[l,2-a]pyrimidin-4-one Intermediate 1-K, (4-(2,2,2-trifluoroethoxy )pheny l)boroni c acid (Combi-Blocks Inc.) 1-36 F _ X X J 'F o         F methyl 4-oxo-3-(4-(2,2,2-trifluoroethoxy)ph enyl)-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidine-8-carboxylate Intermediate 1-D, (4-(2,2,2-tri fluoroethoxy )phenyl)boroni c acid (Combi-Blocks Inc.) 1-37 5 o c# ° Q O™ j-(4- (cycl opropy Imetho xy)phenyl)-8-methoxy-2-(trifluoroniethyl)-4H-pyrimido[l,2-a]pyrimidin-4-one Intermediate 1-0, [4-(cyclopropylmethoxy)phenyl ] boranediol (Combi-Blocks Inc.) 1-38 F 11 JI nor 1                 p F 8-methoxy-3-(l~ (4,4,4- ' trifluorobutyl)- 1 H-pyrazol-4-yl)-2- (trifl a orom eth y 1) -4H-pyrimido| 1,2-a]pyrimidin-4-one Intermediates 1-0, 2-E 1-39 r F O «N 7-jj r" n-X I            f Jsx >5% JL / 0      N |                 p r 3-(1-(2,2-difluoropropyl)-lH-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one Intermediate 1-A, 1-(2,2-difluoropropyl)-4-(4,4,5,5 -tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-pyrazole (Intermediate 2-J) 1-40 o . / Ay F h (4-(8-methoxy-4-oxo-2- (trifl u orom eth y 1) -4H-pyrimido[l,2-a]pyrimidin-3-yl)phenoxy)aceton itrile Intermediate 1-0, (4-(cyanom eth oxy)phenyl )boron ic acid (Combi-Blocks Inc.) 1-41 LL o .....\_____U. ,z z-4 O” 3-(4-(2,2-difluoroethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[ 12-a]pyrimidin-4~one Intermediate 1-B, 2-(4-(2,2-difluoroethoxy) -2 -fluorophenyl)-4,4,5,5 -tetramethyl-1,3,2-dioxaborolane (Enamine Ltd) 1-42 ^oJV o rY n            I L L Ji f F F 3-(4-(2,2,2-triflo oroethoxy)ph enyl)-2- (trifluoromethyl)-4H-pyrido|l,2-a]pyrimidin-4-one 3-bromo-2-(trifluoromethyl)pyrido[ 1,2-a]pyrimidin-4-one (Intermediate 1-P), 4-(2,2,2-trifl uoroethoxy)benzeneboron ic acid (Combi-Blocks Inc.) 1-43 W z  ¥=O T! / .....\ Ti     <( > 3-(1 -phenyl-1H-pyrazol-4-yl)-2-(trifl u orom eth y 1) -4H-pyrido[l,2-a]pyrimidin-4-one intermediate 1-P, 1-phenyl-4-(4,4,5,5 -tetramethyl-1,3,2-dioxaborolan-2-yl)- 1H-pyrazole (Combi-Blocks Inc.) 1-44 0 l^SiT0'SF ii 1 ii                 ’ L L JI f F F 8-methoxy-3-(4-(2,2,2- ” trifluoroethoxy)ph enyl)-2-(trifluoromethvl)-4H-pyndo[l,2-a]pyrimidin-4-one Intermediate 1-A, 4-(2,2,2-trifluoroethoxy) benzeneboron ic acid (Combi-Blocks Inc.) 1-45 -O Q o X too ""“a ti "n l> a ji 7-chloro-8-niethoxy-3-H-(2,2,3,3,3-pentafluoropropyl) - IH-pyrazol -4 -yl ] -2- (trifluoroniethyl)-4H-pyndo[l,2-a]pyrimidin-4-one 7-chloro-3-iodo-8-methoxy-2-(trifluoromethyl)-4H-pyrido [ 1,2-a] pyrim idin -4 -one (Intermediate 1-1), Intermediate 2-G 1-46 LL u-$ # a. / \ Z z— / o 3-(1-(4-fluorophenyl) -1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one Intermediate 1-P, [1-(4-fluorophenyl)-lh-pyrazoi-4-yl]boronic add (Combi-Blocks Inc.) 1-47 [j H. / O™3^ c# 8-methoxy-3-(l~ phenyl- 1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one Intermediate l-A. (1-phenyl-1 h -pyrazol -4-y 1 )borom c acid pinacol ester (Combi-Blocks Inc.) 1-48 "5 o O^(  z V# 0 / 3-(3-fluoro-4-(2,2,2-trifluoroethoxy )ph eny 1) -8 -m eth oxy- (trifluoromethyl)-4H-pyrido[l,2-a] pyrimidin-4-one Intermediates 1-A. 2-F 1-49 .2 0 ^Z\ Z ^“tC T1 Xi # O *n t 8-methoxy-3-(4-(trifluoromethoxy) phenyl)-2- (trifl n orom eth y 1) -4H-pyrido[l,2-a]pyrimidin-4-one Intermediate 1-A, 4-(Trifluoromethoxy)benzenebo ronic acid (Oakwood Chemical) 1-50 0 py    F .nxr 0 N N^K_ F F 8-methoxy-3-(4~ (2,2,2- ' trifluoroethoxy)ph enyl)-2-(trifluoromethyl)-4H-pyrimido[ 1,2-a]pynmidin-4~one Intermediate 1-0, 4-(2,2,2-T ri fluoroeth oxy)benzeneboro nic acid (Combi-Blocks Inc.) 1-51 0 L L H f F F 3-(4-(2-fluoroethoxy)phen yl)-8-(methyloxy-d0-2-      ’    ’ (tri fluoromethyl)-4H-pyrido[l,2-a]pyrimidin-4-one Intermediate 1-N, (4-(2-Fluo roeth oxy)phenyl )boronic acid (Combi-Blocks Inc.) 1-52 b o TJ 3-(4-(2,2-difl uoroethoxy)ph enyl)-8- (methyioxy-ds) -2 -(trifluoromethyl)-4H-pyrido|l,2-a]pyrimidin-4-one Intermediate 1-N, 2-(4-(2,2-Di fluoroetboxy)phenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane (Intermediate 2-C) 1-53 V g L L JL / F F 3-(2-fluoro-4-(2,2,2-trifluoroethoxy )ph eny 1) -8 -m eth oxy- (trifluoromethyl)-4H-pyrimido[l,2-a]pynmidin-4-one Intermediate 1-0, (2-fluoro-4-(2,2,2-trifluoroethoxy)phenyi)boroni c acid (Intermediate 2-L) 1-54 0 1 0 JT JL JU. J F k L JI F !            / F 3-(4-(difluoromethoxy) phenyl)-8~ methoxy-2-(trifluoromethyl)-4H-pyrido[ 1,2-a]pyrimidin-4-one Intermediate 1-B, 4-(difluoromethoxy)phenyl boro nic acid (Combi-Blocks Inc.) 1-55 jQVt □sCO^N^N'AC F F 3-(4-(2- fluoroethoxy)phen yl)-8-(methyloxy-ds)-2- (trifluoromethyl)-4H-pyrimido[ 1,2-a]pyrimidin-4-one 3 -Brom o-8-(m ethoxy-ds)-!-(trifluoromethy 1) -4H-pyrimido| 1,2-a]pyrimidm-4-one (Intermediate 1-R), 4- fluoroethoxy)phenylboronic acid (Combi-Blocks Inc.) 1-56 xxV / CT> N )C.^ H       F r 7-(4-(2-fluoroethoxy)phen yl)-8- (trifluoromethyl)-2H-pyrimido[l,2-ajpyrimidine-2,6(lH)-dione Intermediate 1-B, 4-(2-fl uoroe thoxy)phen ylboronic acid (Combi-Blocks Inc.) 1-57 x A A X / f F 3-(4-(2-fluoroethoxy)phen y 1) -8 -methoxy-2 -(trifluoromethyl)-4H-pyrimido[ 1,2-a]pyrimidin-4-one Intermediate 1-B, 4-(2-fluoroethoxy)phenylboromc acid (Combi-Blocks Inc.) 1-58 0 IL .F 0N 2-(fluorom...

Claims

1. A compound of Formula IIor a tautomer thereof, or a pharmaceutically acceptable salt of said compound orsaid tautomer, whereinwhereinRw is H, F, Cl, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -N(CH3)2, -NH(COCH3), -N(CH3)C(=O)F, methyl, ethyl, -CD3, cyclopropyl, -CH=CH2, -OCD3, or 1,3-oxazol-2-yl; wherein the methyl group is optionally substituted with 1 to 3 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2, and -N(CH3)2;Ry is H, F, Cl, -OH, -CN, -CONH2, -NH2, C1-4alkylamino, diC1-4alkylamino, C1-4alkoxy, or C1-4deuteroalkoxyl; wherein the C1-4alkoxy is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, C1-4alkoxy, -NH2, and diC1-4alkylamino;Rx and Rz are independently H, halogen, -OH, -CN, -CONH2, -NH2, C1-4alkylamino, diC1-4alkylamino, C1-4alkoxy, or C1-4deuteroalkoxyl; wherein the C1-4alkoxy is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, C1-4alkoxy, -NH2, and diC1-4alkylamino;Mn-R3 ^SQn-R3R2 is     N     or N"nR3 is C2-6alkyl or C1-3alkoxy; wherein the C2-6alkyl and C1-3alkoxy groups are optionally substituted with 3-5 halogen atoms; andR4 is C1-3alkyl, C1-4haloalkyl, C1-4alkoxy, C1-4haloalkoxy, C3-5cycloalkyl, or C3-5cyclohaloalkyl.

2. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of saidcompound or said tautomer, wherein the compound is2020391161   25 Nov 2025(2R)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile;(2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile;(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-pyrazol-1-yl)acetonitrile;(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)acetonitrile;(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenyl)acetonitrile;(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)acetonitrile;2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)-2-methylpropanenitrile;2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile;2-(difluoromethyl)-3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-4H-pyrido[1,2-a]pyrimidin-4-one;2-(difluoromethyl)-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile;2-(difluoromethyl)-8-methoxy-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-(difluoromethyl)-8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-(difluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-(difluoromethyl)-8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-(fluoromethyl)-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile;2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2,8-dimethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-2020391161   25 Nov 20252-cyclopropyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-ethoxy-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-ethoxy-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;2-ethyl-8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-ethyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-ethyl-8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione;3-(1-(2,2-difluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-{[(1R)-2,2-difluorocyclopropyl]methyl}-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-{[(1S)-2,2-difluorocyclopropyl]methyl}-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-benzofuran-2-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-cyclopropyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-cyclopropyl-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-phenyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-2020391161   25 Nov 20253-(1-propyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(2-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(2-fluoro-4-(trifluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(2-fluoro-6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(3-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(((1R)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(((1S)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione;3-(4-(2,2,2-trifluoroethoxy)phenyl)-2,8-bis(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2-difluoroethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2-difluoroethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2-difluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20253-(4-(2,2-difluoropropoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2-fluoroethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-pyrazol-1-yl)propanenitrile;3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenyl)propanenitrile;3-(4-(cyclopropylmethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(cyclopropylmethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(cyclopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(difluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(5-(2,2,2-trifluoroethoxy)-2-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(5-fluoro-6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-[5-iodo-1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,3-triazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-{1-[(2,2-difluorocyclopropyl)methyl]-1H-pyrazol-4-yl}-7-fluoro-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-{1-[(2,2-difluorocyclopropyl)methyl]-1H-pyrazol-4-yl}-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20253-{1-[(3,3-difluorocyclobutyl)methyl]-1H-pyrazol-4-yl}-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile;4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylic acid;4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile;4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide;4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylic acid;4-oxo-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-7-carbonitrile;7-(methoxymethyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-chloro-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;7-chloro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-chloro-8-methoxy-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;7-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-chloro-8-methyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;7-chloro-8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-chloro-8-methyl-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-cyclopropyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;7-cyclopropyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20257-fluoro-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;7-fluoro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-fluoro-8-hydroxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-fluoro-8-methoxy-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;7-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-fluoro-8-methoxy-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-fluoro-8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((1R)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((1R)-1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((1S)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((1S)-1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((dimethylamino)methyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methyloxy-d3)-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((methylsulfanyl)methoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((R)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20258-((R)-methylsulfinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((R)-methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((S)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((S)-methylsulfinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((S)-methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(1,3-oxazol-2-yl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(2-hydroxypropan-2-yl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(2-methyl-2-oxetanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(2-propanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(3-azetidinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(aminomethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(1-azetidinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(chloromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(difluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(difluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20258-(dimethylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(dimethylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(fluoromethoxy)-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(fluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(fluoromethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(fluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(hydroxymethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(hydroxymethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methoxymethyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methyl-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methyloxy-d3)-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20258-(methyloxy-d3)-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylsulfanyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylsulfanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylsulfinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylsulfonyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-acetyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-amino-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-chloro-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-cyclopropyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-cyclopropyl-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-ethenyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-ethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-ethyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-fluoro-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20258-methoxy-2-(trifluoromethyl)-3-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-imidazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-(4-(3,3,3-trifluoropropyl)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-[3-(3,3,3-trifluoropropyl)-1,2-oxazol-5-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-[4-(3,3,3-trifluoropropyl)-1H-imidazol-1-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,3-thiazol-2-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-phenyl-1H-pyrazol-3-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-phenyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-propyl-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(2-phenyl-1,3-oxazol-5-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20258-methoxy-3-(3-phenyl-1,2-oxazol-5-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(4-(2,2,3,3,3-pentafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(4-(2,2,3,3-tetrafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(4-propylphenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(5-propyl-1,2-oxazol-3-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(6-propyl-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,3-triazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[2-(2,2,2-trifluoroethoxy)-1,3-thiazol-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[2-(2,2,3,3,3-pentafluoropropoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[3-(2,2,3,3,3-pentafluoropropyl)-1,2-oxazol-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[4-(2,2,2-trifluoroethoxy)-1,3-thiazol-2-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20258-methoxy-3-[5-(2,2,2-trifluoroethoxy)-1,3-thiazol-2-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-{1-[(oxetan-3-yl)methyl]-1H-pyrazol-4-yl}-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-6-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methyl-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,2,4-oxadiazol-3-yl]-4H-pyrido[1,2-a]pyrimidin-4-one;8-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;9-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;9-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;methyl        4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylate;methyl(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)carbamyl fluoride;N-(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)acetamide;N-(4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)acetamide;N,N-dimethyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide;N-ethyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide;N-methyl-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide; orN-methyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide.

3. A compound, or a tautomer thereof, or a pharmaceutically acceptable salt of saidcompound or said tautomer, wherein the compound is(2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile;2020391161   25 Nov 20252-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)-2-methylpropanenitrile;2-(difluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2,8-dimethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-cyclopropyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-ethoxy-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2-ethyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione;3-(1-(2,2-difluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(2-fluoro-4-(trifluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4,8(1H)-dione;3-(4-(2,2-difluoroethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2,2-difluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20253-(4-(2,2-difluoropropoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(cyclopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile;4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxamide;7-chloro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;7-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((1R)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((1S)-1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-((dimethylamino)methyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(aminomethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(dimethylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(fluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(hydroxymethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(hydroxymethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methoxymethyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;2020391161   25 Nov 20258-(methylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-amino-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-ethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,3-triazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; or8-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one.

4. The compound according to claim 2, or a tautomer thereof, or a pharmaceuticallyacceptable salt of said compound or said tautomer, wherein the compound is2020391161   25 Nov 20254-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile;8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; or8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one.

5. The compound according to claim 2, or a pharmaceutically acceptable salt thereof,wherein the compound is6.     The compound according to claim 2, or a tautomer thereof, or a pharmaceuticallyacceptable salt of said compound or said tautomer, wherein the compound is7.     The compound according to claim 2, or a pharmaceutically acceptable salt thereof,wherein the compound is2020391161   25 Nov 20258.     The compound according to claim 2, or a pharmaceutically acceptable salt thereof,wherein the compound is9.     The compound according to claim 2, or a pharmaceutically acceptable salt thereof,wherein the compound is10. A pharmaceutical composition comprising the compound according to any one of claims 1 to 9, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable excipient.Amgen Inc.Patent Attorneys for the Applicant / Nominated Person SPRUSON & FERGUSON

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