HETEROCYCLIC COMPOUNDS AS DELTA-5 DESATURASE INHIBITORS AND METHODS OF USE

Abstract

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

Description

HETEROCYCLIC COMPOUNDS AS DELTA-5 DESATURASE INHIBITORS AND METHODS OF USE CROSS-REFERENCE TO RELATED APPLICATION This application claims the 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 inhibiting Delta-5 Desaturase (“D5D”). This disclosure also provides pharmaceutical compositions comprising the compounds, uses of the compounds, and compositions for treating, for example, a metabolic or cardiovascular disorder. In addition, the disclosure provides intermediates useful in the synthesis of compounds of Formula I. BACKGROUND Polyunsaturated fatty acids (PUFAs) perform important physiological functions in the human body. Kroeger J and Schulze MB, 2012, p. 4. PUFAs serve as energy sources 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 Matías I, 2005, p. 585. Eicosanoids are signaling molecules that play multiple roles and regulate, among other things, the human inflammatory response. Harizi H et al., 2008. The endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) are endogenous ligands for cannabinoid receptors that have been shown to play a role in food intake and energy balance. Di Marzo V and Matías I, 2005, p. 585. Figure 1 shows the relevant part of the metabolic pathway for a particular PUFA, linoleic acid (“LA”), which leads, among other things, to the formation of anti- and pro-inflammatory endocannabinoids and eicosanoids. Yashiro H et al., 2016, page 2 / 18. Obukowicz MG et al., 1998, page 158. Di Marzo V and Matías I, 2005, page 585. Desaturase enzymes, which catalyze certain steps in the conversion of LA to AA, are delta-6-desaturase (“D6D”; encoded by the fatty acid desaturase 2 gene (FattyAcid Desaturase 2, “FADS2”) and delta-5-desaturase (“D5D”; encoded by the fatty acid desaturase 1 gene (Fatty Acid Desaturase 1, “FADSr”). Yashiro H et al., 2016, page 2 / 18. Selectively inhibiting D5D activity reduces the amount of AA generated, while increasing the amount of DGLA. Such a pharmacological intervention reduces the further generation of, for example, pro-inflammatory endocannabinoids and eicosanoids, and leads to the accumulation of anti-inflammatory eicosanoids, both of which can collectively improve inflammatory conditions and may improve energy balance. Yashiro H et al., 2016, page 3 / 18. Di Marzo V and Matías I, 2005, page 585.This is especially relevant in subjects with a high LA intake, e.g., humans exposed to Western-style diets. Yashiro H etal., 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. Fumagallí M et al., 2015. Willer CJ et al., 2013. Dupuis J et al., 2010. An increase or elevation of each metabolic trait is associated with the FADS1-3 locus is also associated with an increase in D5D activity as determined by AA:DGLA ratios. Fumagallí M etal., 2015. Merino DM et al., 2011. In addition to human genetic evidence supporting a role for FADS1ID5D in metabolic disorders, FADS1 knockout (“KO”) mice also exhibit a diet-induced obesity-protective phenotype that includes low body fat, improved glycemic control, and decreased circulating lipid levels. Powell DR et al., 2016, p. 197. Furthermore, FADS1 KO mice are resistant to the development of atheromatous plaques in arteries. Id. Desaturase enzyme activity has been linked to a variety of diseases, particularly metabolic and cardiovascular diseases such as obesity, diabetes, nonalcoholic steatohepatitis (NASH), dyslipidemia, and coronary artery disease. Tosí F et al., 2014; Kroeger J and Schulze MB, 2012; and Merino DM et al., 2010. Therefore, pharmacological inhibition of D5D is an interesting target for the treatment of metabolic, cardiovascular, and other diseases. Powell DR et al., 2016, p. 197. Despite some progress in the field of low molecular weight therapeutic agents (e.g. Miyahisa I et al., 2016; Yashiro H et al., 2016; and Baugh SD et al., 2015), there is still a need for D5D inhibitors that may be suitable for use as therapeutic agents in view of the significant ongoing burden on society caused by, e.g., metabolic and cardiovascular diseases (e.g. Haidar YM and Cosman BC, 2011; Mendis S et al., 2007; Chopra M et al., 2002; and Monteiro CA et al., 2004). COMPENDIUM First, provided herein is a compound of Formula I EITHER or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein where Rwes H, halogen, -CN, -CO(Cm alkyl), -S(O)n(Cu alkyl), -COOH, -COO(C1-4 alkyl), -CONH2, -CONH(Cm alkyl), -CO(di(Cm alkyl)amino), -NH2, (Cm alkyl)amino, di(Cm alkyl)amino, -NH(CO(C14 alkyl)), -N(Cm alkyl)C(=O)F, C14 alkyl, C14 deuteroalkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl, C2-4 alkenyl, Cm deuteroalkoxy or 5-membered heteroaryl; wherein the Cm alkyl and C3-4 heterocycloalkyl groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, -CN, C1-4 alkoxy, C1-4 alkyl, -NH2, (Cm alkyl examino, di(Cm alkyl)amino, and -S(O)n(Cm alkyl); Ry is H, F, Cl, -OH, -CN, -CO(C1-4 alkyl), -S(O)n(C1-4 alkyl), -COOH, -COO(Cm alkyl), -CONH2, -CONH(Cm alkyl), -CO(di(Cm alkyl)amino), -NH2, (Cm alkyl)amino, di(Cm-4 alkyl)amino, -NH(CO(Cm alkyl)), -N(Cm alkyl)C(=O)F, Cm alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl, C2-4 alkenyl, Cm alkoxy, Cm deuteroalkoxy or 5-membered heteroaryl; where the Cm alkyl, C3-4 heterocycloalkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, Cm alkyl, -NH2, (Cm alkyl, di(Cm alkyl)amino and S(O)n(Cm alkyl); Rx and Rx are independently H, halogen, -OH, -CN, -CO(Cm alkyl), S(O)n(Cm alkyl), -COOH, -COO(Cm alkyl), -CONH2, -CONH(Cm alkyl), -CO(di(Cm alkyl)amino), -NH2, (Cm alkyl)amino, di(Cm alkyl)amino, -NH(CO(Cm alkyl)), -N(C1 alkyl 4)C(=O)F, Cm alkyl, Cm deuteroalkyl, C3.5 cycloalkyl, C3-4 heterocycloalkyl, C24 alkenyl, C1.4 alkoxy, C1.4 deuteroalkoxy or 5-membered heteroaryl; wherein the C14 alkyl, C3-4 heterocycloalkyl and C1.4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, Cm alkyl, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, and -S(O)n(C1-4 alkyl); R1 is H, C1-4 alkyl, C14 haloalkyl or C14 deuteroalkyl; x is O, NH or N(C1-4 alkyl); R2 is A , A R3,l~-~ / or 2-benzofuranyl, where A is independently CH or N, and where B is a 5-membered heteroaryl containing one heteroatom selected from N, S and O, and optionally one or two additional N atoms, where (i) B is bonded through a C atom to the bicyclic nucleus and R3 is bonded through an N atom; or (ii) B is bonded through an N atom to the bicyclic nucleus and R3 is bonded through a C atom; or (iii) B is bonded through a C atom to the bicyclic nucleus and R3 is bonded through a C atom; W and where the portion A , A e0~ / qer2o e| 2benzofuranyl is further optionally substituted with one or two independently selected R3' substituents; R3 is CH2CN, C2-6 alkyl, C3-5 cycloalkyl, C1.3 alkoxy, (C1-6 alkyl)amino, di(C16 alkyl)amino, -S(O)n(C1-e alkyl), -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl), NHCH2(C3-5 cycloalkyl), -S(O)nCH2(C3-5 cycloalkyl), -CH2(C3-5 heterocycloalkyl) or phenyl; wherein C2-6 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, (C1-3 alkylamino, di(C1-6 alkyl)amino, -S(O)n(C1-e alkyl), -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl), -NHCH2(C3-5 cycloalkyl) and -S(O)nCH2(C3-5 cycloalkyl) groups are optionally substituted with 1-9 halogen atoms and are optionally substituted with -CN and wherein phenyl is optionally substituted with 1-3 substituents selected from halogen, C1.4 alkyl, C1.4 haloalkyl, C1.4 alkoxy and C1-4 haloalkoxy; R3' is independently halogen, C1.4 alkyl, Cm haloalkyl, C1.4 alkoxy or C1.4 haloalkoxy; R4 is C1-3 alkyl, Cm haloalkyl, C14 alkoxy, C14 haloalkoxy, C3-5 cycloalkyl, or C3-5 cyclohaloalkyl; and n is 0, 1, or 2. Secondly, 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 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 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 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 the treatment of a metabolic disorder or for use in the treatment of 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 the treatment of a metabolic disorder or for use in the treatment of diabetes, obesity, dyslipidemia or non-alcoholic steatohepatitis (NASH). Reference will now be made in detail to embodiments of the present disclosure. Although certain embodiments of the present disclosure will be described, it is to be understood that the embodiments of the present disclosure are not intended to be limited to those described embodiments. Rather, reference to embodiments of the present disclosure is intended to encompass alternatives, modifications, and equivalents that may be included within the nature and scope of the embodiments of the present disclosure as defined in the appended claims. BRIEF DESCRIPTION OF THE FIGURES Figure 1 shows part of the LA metabolic pathway, leading to the formation of anti- and pro-inflammatory endocannabinoids and eicosanoids. DETAILED DESCRIPTION Provided herein as Embodiment 1 is a compound of Formula I EITHER I or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 1) Rz Rw, where optionally one of CRW, CRX, CRyy CR2es N; where Rwes H, halogen, -CN, -CO(Cm alkyl), -S(O)n(Cu alkyl), -COOH, -COO(C1-4 alkyl), -CONH2, -CONH(Cm alkyl), -CO(di(Cm alkyl)amino), -NH2, (Cm alkyl)amino, di(alkyl examino, -NH(CO(C1-4 alkyl)), -N(Cm alkyl)C(=0)F, Cm alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl, C2-4 alkenyl, Cm deuteroalkoxy or 5-membered heteroaryl; where the Cm alkyl and C3-4 heterocycloalkyl groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, -CN, Cm alkoxy, Cm alkyl, -NH2, (Cm alkyl)amino, di(Cm alkyl)amino, and -S(O)n(Cm alkyl); Ryes H, F, Cl, -OH, -CN, -CO(Cm alkyl), -S(O)n(Cm alkyl), -COOH, -COO(Cm alkyl), -CONH2, -CONH(Cm alkyl), -CO(di(alkyl CuJamino), -NH2, (Cm alkyl)amino, di(alkyl CuJamino, -NH(CO(Cm alkyl)), -N(Cm alkyl)C(=O)F, Cm alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl, C2-4 alkenyl, Cm alkoxy, Cm deuteroalkoxy or 5-membered heteroaryl; where the Cm alkyl, C3-4 heterocycloalkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, C1.4 alkoxy, Cm alkyl, -NH2, (Cyclamino alkyl, di(CM alkyl)amino and S(O)n(C1-4 alkyl); Rx and Rz are independently H, halogen, -OH, -CN, -CO(C1-C2 alkyl), S(O)n(C3 alkyl), -COOH, -COO(C4 alkyl), -CONH2, -CONH(C1-C4 alkyl), -CO(di(C4 alkyl)amino), -NH2, (C5 alkyl)amino, di(C5 alkyl)amino, -NH(CO(C6 alkyl)), -N(C14 alkyl)C(=O)F, C6 alkyl, C6 deuteroalkyl, C3-C5 cycloalkyl, C6 heterocycloalkyl, C2-C4 alkenyl, C6 alkoxy, C6 deuteroalkoxy or 5-membered heteroaryl; where the Cm alkyl, Cm heterocycloalkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, Cm alkyl, -NH2, (Cm alkyl)amino, di(C1-4 alkyl)amino, and -S(O)n(C1-4 alkyl); R1 is H, Cm alkyl, Cm haloalkyl or Cm deuteroalkyl; x is O, NH or N(Cm alkyl); AV / A3|(β)λR R2 is A;AR , '-—I 2-benzofuranyl, where A is independently CH or N, and where B is a 5-membered heteroaryl containing one heteroatom selected from N, S and O, and optionally one or two additional N atoms, where (i) B is bonded through a C atom to the bicyclic nucleus and R3 is bonded through an N atom; or (i) B is bonded through an N atom to the bicyclic nucleus and R3 is bonded through a C atom; or (iii) B is bonded through a C atom to the bicyclic nucleus and R3 is bonded through a C atom; and where the portion A, A0'-—and of r2o and e| benzofuranyl is further optionally substituted with one or two independently selected R3' substituents; R3 is CH2CN, C2-6 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, (alkyl examino, di(C , -e alkyl)amino, -S(O)n(C1-e alkyl), -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl), NHCH2(C3-5 cycloalkyl), -S(O)nCH2(C3-5 cycloalkyl), -CH2(C3.s heterocycloalkyl) or phenyl; where the C2-6 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, (alkyl examino, di(alkyl examino, -S(O)n(C1-B alkyl), -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl), -NHCH2(C3-s cycloalkyl) and -S(O)nCH2(C3-5 cycloalkyl) are optionally substituted with 1-9 halogen atoms and are optionally substituted with -CN and wherein the phenyl is optionally substituted with 1-3 substituents selected from halogen, Cu alkyl, C1.4 haloalkyl, C1-4 alkoxy and C1-4 haloalkoxy; R3' is independently halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy or C1.4 haloalkoxy; R4 is C1-3 alkyl, C1-4 haloalkyl, C14 alkoxy, C14 haloalkoxy, C3-5 cycloalkyl, or C3-5 cyclohaloalkyl; and 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¡)pyrimidin-5-yl]-2-(trifluoromethyl)-4H,6H,7H,9H-pyrimído[2,1c][1,4]oxazin-4-one; 7-(azetidin-1-íl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpí rido[ 1,2-a]pyrimidín-4-one; 7-[(dimethylamino)methyl]-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 7-chloro-3-[2-(2,2,2-trifluoroethoxy¡)p¡nm¡d¡n-5-¡l]-2-(thfluoromet¡l)-4H-p¡r¡do[1,2-a]p¡rim¡d¡n4-one; 7-cyclopropyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(tnfluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 7-fluoro-3-[2-(2,2,2-trifluoroethoxy)pyrimidine-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 7-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrimido[1,2-b]pyridazn-4-one; 7-methoxy-3-[2-(2,2,2-tr¡fluoroethox¡)param¡d¡n-5-¡l]-2-(tr¡fluoromet¡l)-4H-pyrimido[1,2b]pyridazin-4-one; 7-methyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrazino[1,2a]pyrimidin-4-one; 7-methyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazin-4-one; 8-methoxyl-3-[1-(2,2,3,3,3-pentafluoropropl)-1H-1,2,4-thazol-3-l]-2-(trfluorometl)-4Hprido[1,2-a]pihrmdln-4-one; 8-methoxy-3-[3-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; or 4-oxo-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l]-2-(tr¡fluoromet¡l)-4H-p¡hdo[1,2a]pyrimidin-7-carbox¡lato de methylo. 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 RzO AI. Provided herein as Embodiment 4 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 IB RzO Rw 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 EITHER Rw 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 said compound or said tautomer, wherein Rwes H, halogen, -CN, -CO(C1-4 alkyl), -S(O)n(Cm alkyl), -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, -NH(CO(C1-4 alkyl)), -N(C1-4 alkyl)C(-O)F, Cu alkyl, C1-4 deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, C14 deuteroalkoxy or 5-membered heteroaryl; wherein the C1.4 alkyl group is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, C1-4 alkoxy, -NH2 and di(C1-4 alkyl)amino. 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 Rwes H, halogen, -CN, -CONH2, -NH2, (alkyl Ci.4)amino, di(alkyl examino or deuteroalkoxy Cu; where the alkyl group Cu is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, alkoxy Cu, -NH2 and di(alkyl Ciu)amino. 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 Rwes 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; where 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 Rwes H, F, Cl, -CN, -CONH2, -NH2, -NHMe or -OCD3; where 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 Rwes H, halogen or C1.4 alkyl. 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 Rwes 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 Rwes 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 Rxes H, halogen, -OH, -CN, -CO(C1-4 alkyl), -S(O)n(C1-4 alkyl), -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, -NH(CO(C1-4 alkyl)), -N(C1-4 alkyl)C(=O)F, C14 alkyl, C1^ deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, C^ alkoxy, C14 deuteroalkoxy or 5-membered heteroaryl; where the Cm alkyl and C1.4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, -NH2 and di(C1^ alkyl)amino. 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 Rxes H, halogen, -OH, -CN, -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, Cm alkoxy or deuteroC1-4 alkoxy; where the C1-4 alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, C« alkoxy, -NH2 and di(C1-4 alkyl)amino. 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 Rxes 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, -OCD3O 1,3-oxazol-2-yl; where 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 Rxes H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy or -OCD3; where 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 Rxes H, halogen, -OH, -CN, -CO(C1.4 alkyl), -S(O)n(C1.4 alkyl), -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, -NH(CO(C1.4 alkyl)), -N(C1-4 alkyl)C(=O)F, C4 alkyl, C3-5 cycloalkyl, C2-4 alkenyl, Cm alkoxy, C« deuteroalkoxy or 5-membered heteroaryl; where the C1-4 alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, -NH2 and di(C1-4 alkyl)amino. 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 Rxes H, halogen, -OH, -CN, -CONH2, -NH2, (alkyl examino, di(alkyl examino, Cm alkyl, C1-4 alkoxy or Cm deuteroalkoxy; where the Cm alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, Cm alkoxy, -NH2 and di(Ci-4 alkyl)amino. 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 Rxes H, -CN, -NH2, C1-4O alkoxy deuteroalkoxy Cm. 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 Rxes H, F, Cl, -OH, -CN, -COMe, -SMe, -CONH2, -NH2, -NHMe, -NH(CH3)2, NH(COCH3), -N(CH3)C(=O)F, methyl, ethyl, cyclopropyl, -CH=CH2, methoxy, ethoxy, -OCD3 or 1,3-oxazol-2-yl; where the methyl and methoxy groups are optionally substituted with 1 to 4 substituents independently selected from F, Cl, -OH, -CN, methoxy, -NH2 and -N(CH3)2. 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 Rxes H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methyl, methoxy, ethoxy or -OCD3; where the methyl and methoxy groups are optionally substituted with 1 to 4 substituents independently selected from F, -OH, methoxy, -NH2 and -N(CH3)2. Provided herein as Embodiment 22 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 Rxes H, -CN, -NH2, methoxy or -OCD3. 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 Rv is H, F, Cl, -OH, -CN, -CO(C1.4 alkyl), -S(O)n(Cm alkyl), -CONH2, -NH2, (C14 alkyl)amino, di(Cm alkyl)amino, -NH(CO(Cm alkyl)), -N(Cm alkyl)C(=O)F, Cm alkyl, Cm deuteroalkyl, C3.5 cycloalkyl, C2-4 alkenyl, Cm alkoxy, Cm deuteroalkoxy or 5-membered heteroaryl; wherein the C1.4 alkyl and C1.4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, C14 alkoxy, -NH2 and di(Cm^ alkyl)amino. 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 Ryes H, F, Cl, -OH, -CN, -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, Cm alkoxy or deuteroC1.4 alkoxy; where the C1.4 alkyl and C1.4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, C1-4 alkoxy, -NH2 and di(C1-4 alkyl)amino. 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 Ryes 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, -OCD3O 1,3-oxazol-2-yl; where 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 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 Ryes H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy or -OCD3; where 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 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(C1-4 alkyl), C1-4 alkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl or Cm alkoxy; where the Cm alkyl group is optionally substituted with 1 to 4 substituents independently selected from C« alkoxy and di(C1-4 alkyl)amino. 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 Ryes H, F, Cl, -CN, -COOMe, methyl, cyclopropyl, azetidinyl or methoxy; where 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 Ryes 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 Rzes H, halogen, -OH, -CN, -CO(Cm alkyl), -S(O)n(Cm alkyl), -CONH2, -NH2, (Cm-4 alkyl)amino, di(Cm-4 alkyl)amino, -NH(CO(C1-4 alkyl)), -N(Cm-4 alkyl)C(=O)F, C4 alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, Cm alkoxy, Cm deuteroalkoxy or 5-membered heteroaryl; where the Cm alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, -NH2 and di(Cm alkyl)amino. 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 Rzes H, halogen, -OH, -CN, -CONH2, -NH2, (Cm-alkyl)amino, di(Cm-alkyl)amino, Cm-alkoxy or Cm-deuteroalkoxy! where the Cm-alkyl and Cm-alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, Cm-alkoxy, -NH2 and di(Ci-4-alkyl)amino. 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 Rzes 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, -OCD3O 1,3-oxazol-2-yl; where 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 Rzes H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy or -OCD3; where 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 Rzes H or alkyl Cm. 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 Rzes 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 Rzes 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 R- O Yo R1 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 Ryes H, F, Cl, -OH, -CN, -CO(C1-4 alkyl), -S(O)n(Cm alkyl), -CONH2, -NH2, (C1-4 alkyl)amino, di(C-4 alkyl)amino, -NH(CO(C1-4 alkyl)), -N(C1-4 alkyl)C(=O)F, C1-4 alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, C« alkoxy, C1-4 deuteroalkoxy or 5-membered heteroaryl; where the C« alkyl and C1-4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, C1-4 alkoxy, -NH2 and di(C1-4 alkyl)amino. 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 Ryes H, F, Cl, -OH, -CN, -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, C1-4 alkoxy or deuteroC1-4 alkoxy; where the C1-4 alkyl and C1-4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, Cm alkoxy, -NH2 and di(C1-4 alkyl)amino. 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 Ryes 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, -OCD3O 1,3-oxazol-2-yl; where 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 41 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ryes H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy or -OCD3; where 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 42 is the compound according to Embodiment 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ryes H, F, Cl, -CN, -COO(Cm alkyl), C1-4 alkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl or C« alkoxy; where the Cm alkyl group is optionally substituted with 1 to 4 substituents independently selected from Cm alkoxy and di(Cm-4 alkyl)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 Ryes H, F, Cl, -CN, -COOMe, methyl, cyclopropyl, azetidinyl or methoxy; where 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 Ryes 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 Rzes H, halogen, -OH, -CN, -CO(C1.4 alkyl), -S(O)n(C1.4 alkyl), -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl^amino, -NH(CO(C1.4 alkyl)), -N(C1-4 alkyl)C(=O)F, C4 alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C2.4 alkenyl, Cm alkoxy, Cm deuteroalkoxy or 5-membered heteroaryl; where the Cm alkyl and C1.4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, 0« alkoxy, -NH2 and di(C1^ alkyl)amino. 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 Rzes H, halogen, -OH, -CN, -CONH2, -NH2, (alkyl examino, di(alkyl Ci^)amino, C1-4 alkoxy or deuteroC1-4 alkoxy; where the C1-4 alkyl and alkoxy Cu groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, C1-4 alkoxy, -NH2 and di(alkyl examino. 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 Rzes 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 1,3-oxazol-2-yl; where 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 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 Rzes H, F, Cl, -OH, -CN, -CONH2, -NH2, -NHMe, methoxy, ethoxy or -OCD3; where 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 Rzes H, halogen or alkyl Ci^ 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 Rzes H, F, Cl or methyl. 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 Rzes 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, CH2F 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 R1 is H. 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 I is a compound of Formula IE EITHER 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 O. 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. 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(Cm alkyl). 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 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 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 R2es 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 —' , where 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 bonded through a C atom to the bicyclic nucleus and R3 is bonded through 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 bonded through an N atom to the bicyclic nucleus and R3 is bonded through 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 bonded through a C atom to the bicyclic nucleus and R3 is bonded through 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, where R2 is ^N'μ! 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 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 compound or said tautomer, wherein the "A" portion, A0 of R2 or the 2-benzofuranyl is further optionally substituted with an R3' substituent. 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 compound or said tautomer, wherein the A' portion of R3 or the 2-benzofuranyl is not further substituted with one or two substituents. R3selected independently. 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 R3 is C2-6 alkyl, C1.3 alkoxy, -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl) or phenyl; where the C2-6 alkyl, C1.3 alkoxy, -CH2(C3-5 cycloalkyl) and -OCH2(C3-5 cycloalkyl) groups are optionally substituted with 1 to 5 halogen atoms and are optionally substituted with -CN and where the phenyl is optionally substituted with a 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 R3 is C2-6 alkyl, C1.3 alkoxy or -OCH2(C3-5 cycloalkyl); where the C2-6 alkyl, C1.3 alkoxy and -OCH2(C3-5 cycloalkyl) 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 C2-6 alkyl or C1.3 alkoxy; where the C2-e and C1.3 alkoxy 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 R3is 2,2,2-trifluoroethyl, propyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, 4,4,4trifluorobutyl, 2,2,3,3,3-pentafluoropropyl, -OCH2CN, -OC(CH3)2CN, difluoromethoxy, trifluoromethoxy, -OCH(CN)CH3, 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, (2,2difluorocyclopropyl)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 R3is 2,2-difluoropropyl, 4,4,4-trifluorobutyl, 2,2,3,3,3-pentafluoropropyl, OC(CH3)2CN, trifluoromethoxy, -OCH(CN)CH3, 2-fluoroethoxy, 2,2,-difluoroethoxy, 2,2,2trifluoroethoxy, 2,2-difluoropropoxy, cyclopropylmethoxy or (2,2-difluorocyclopropyl)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' is independently halogen or Cmalkyl. 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 F or 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 C1-3 alkyl, Cm haloalkyl, Cm alkoxy or C3-5 cycloalkyl. 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 C1.3 haloalkyl. 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, difluoromethyl, trifluoromethyl, methoxy, ethoxy or cyclopropyl. 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. In the present case, the compound of the compound is proposed as Realization 90 with Realization 1, or a tautómero de este, or a pharmaceutically acceptable solution of this compound or of that tautómero, from which the compuesto is (2R)-2-(4-(8-methox¡-4-oxo-2-(tr¡fluoromet¡l)-4H-pyr¡do[1,2-a]pyrimidin-3yl)phenoxy)propanon¡tr¡lo; (2R)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrimodo[1,2-a]pyrmidin-3yl)phenoxy)propanonitrile; (2S)-2-(4-(8-methox¡-4-oxo-2-(trifluoromet¡l)-4H-p¡r¡do[1,2-a]pyrimidin-3yl)phenox¡)propanon¡trilo; (2S)-2-(4-(8-methox¡-4-oxo-2-(tr¡fluoromet¡l)-4H-pyr¡m¡do[1,2-a]pyrimidin-3¡l)phenoxy)propanon¡tr¡lo; (4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-p¡r¡do[1,2-a]pyrimidi η-3-yl)-1 H-pyrazol-1yl)acetonitrile; (4-(8-methox¡-4-oxo-2-(trifluorometh¡l)-4H-pyrido[1,2-a]p¡r¡m¡din-3-yl)phenox¡)acetone¡tr¡lo; (4-(8-methox¡-4-oxo-2-(trifluoromet¡l)-4H-pyrido[1,2-a]p¡r¡m¡d¡n-3-yl)phen¡l)acetone¡tr¡lo; (4-(8-methox¡-4-oxo-2-(tr¡fluoromet¡l)-4H-pirim¡do[1,2-a]p¡r¡midin-3-yl)phenoxy)acetonitrile; (4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-yl)-2-(trifluoromet¡l)-4H-pyrido[1,2a]pyr¡m¡d¡n-8-yl)aceton¡trilo; 1-(chloromethyl)-7-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-yl]-8-(tr¡fluoromet¡l)1 H,2H,6H-pyrim¡do[1,2-a][1,3]diazin-2,6-diona; -(fluoromethyl)-7-[1 -(2,2,3,3,3-pentafluoropropyl)-1 Hp¡ razo l-4-i I ]-8-(trifl u orom eti I )- H,2H,6H-[1,3]diazine[1,2-a]pyrimidin-2,6-diona; 1-(methyl-d3)-7-(4-(2,2,2-trifluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyrimid[1,2-a]pyrimidin- 2,6(1 H)-dione; 1-methyl-7-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-8-(trifluoromethyl)-1H,2H,6H[1,3]diazine[1,2-a]p¡rimidin-2,6-diona; 2-(4-(8-methox¡-4-oxo-2-(trifluoromet¡l)-4H-p¡r¡do[1,2-a]p¡r¡m¡d¡n-3-yl)phenox¡)-2methylpropanonitrile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3yl)phenoxy)propanenitrile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-3-yl)phenoxy)propanonetrilo; 2-(difluoromethyl)-3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-4H-pyrido[1,2a]pyrimidin-4-one; 2-(difluoromethyl)-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidine-8-carbonitrile; 2-(difluoromethyl)-8-methoxy-3-(1-(3,3,3-trifluoroprop¡l)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyramid¡n-4-one; 2-(difluoromethyl)-8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-8-carbonyl; 2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidine-4-one; 2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H,6H,7H,9H-pyrimido[2,1c][1,4]oxazin-4-one; 2,8-d¡methoxy¡-3-(4-(2,2,2-tr¡fluoroethox¡)phen¡l)-4H-pyr¡do[1,2-a]pyrim¡d¡n-4-one; 2-cyclopropyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-parado[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-ethox¡-8-methoxy¡-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-¡l]-4H-p¡r¡do[1,2a]pyrim¡d¡n-4-one; 2-ethyl-8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]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-pyr¡dinyl)-4H-p¡r¡do[1,2-a]p¡rimidin-4-one; 3-(1 -(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazole-4-i I )-2-(trifl uoromethyl )-4H-pi curtain[1,2a]pyrimi¡n-4,8(1 H)-dione; 3-(1-(2,2-difluoroprop¡l)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimid¡n-4-one; 3-(1-(3-fluoroprop¡l)-1H-pyrazol-4-¡l)-8-methox¡-2-(trifluorometh¡l)-4H-pyrido[1,2-a]pinm¡din4-one; 3-(1-(4-fluorophen¡l)-1H-pyrazol-4-yl)-2-(tr¡fluoromethyl)-4H-p¡r¡do[1,2-a]pyr¡midin-4-one; 3-(1 -(4-fluoropropyl)-1 Hp¡razol-4-yl)-8-methoxy-2-(tr¡fluoromethyl)-4H-p¡r¡do[1,2-a]pyrimidin4-one; 3-(1-{[(1 R)-2,2-d¡fluorocycloprop¡l]meth¡l}-1H-p¡razol-4-¡l)-8-methox¡-2-(trifluorometh¡l)-4Hp¡ curtain[ 1,2-a]pinm¡din-4-one; 3-(1-{[(1S)-2,2-difluorocyclopropyl]methyl}-1 H-pyrazol-4-¡l)-8-methoxy-2-(trifluoromet¡l)-4Hpyrido[1,2-a]pyrimid¡n-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-(trifluorometl)-4H-pyrido[1,2-a]pyramidal-4-one; 3-(1-cyclopropyl-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4one; 3-(1-phenyl-1-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[1,2a]pyrimidine-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[1,2a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2a]pyrimidin-4-one; 3-(2-Fluoro-4-(trifluoromethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4one; 3-(2-fluoro-6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2a]pyrimidin-4-one; 3-(4-(((1 R)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-(4-(((1S)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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-tr¡fluoroethoxy¡)phen¡l)-2,8-b¡s(tr¡fluoromet¡l)-4H-p¡r¡do[1,2-a]pyrim¡din-4-one; 3-(4-(2,2-d¡fluoroethoxy¡)-2-fluorophen¡l)-8-methoxy¡-2-(tr¡fluoromet¡l)-4H-pyrido[1,2-a]pyrim¡d¡n4-one; 3-(4-(2,2-difluoroethoxy)phenyl)-8-(met¡lox¡-d¡3)-2-(tr¡fluoromet¡l)-4H-pyrido[1,2-a]pyr¡m¡d¡n-4one; 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-(methyllox-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-(metoxalox-d3)-2-(trifluoromethyl)-4H-paramido[1,2-a]paramido-n-4one; 3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-para[1,2-a]paramidin-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin η-3-yl)-1H-pyrazol-1 yl)propanonitrilo; 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyramidal-3-yl)phenyl)propanone; 3-(4-(cyclopropylmethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-(4-(cyclopropalmetox)phenl)-8-(metloxal-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyralmandlan-4one; 3-(4-(cyclopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(4-(cyclopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[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-pyrimidinyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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,6H,7H,9Hpyrimido[2,1-c][1,4]oxazin-4-one; 3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrazino[1,2a]pyrimidin-4-one; 3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-[1-(cyclopropylmethyl)-1-pyrazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-8-methyl-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazin-4-one; 3-[5-yodo-1 -(2,2,3,3,3-pentafluoropropil)-1 H-1,2,3-triazol-4-il]-8-metoxi-2(trifluorometil)-4H-pir¡do[1,2-a]pirimidin-4-ona; 3-{1-[(2,2-difluorocicloprop¡l)metil]-1H-pirazol-4-¡l}-7-fluoro-8-metox¡-2-(tr¡fluorometil)4H-p¡r¡do[1,2-a]pirimid¡n-4-ona; 3-{1-[(2,2-difluorociclopropil)inet¡l]-1H-p¡razol-4-il}-8-metox¡-2-(tr¡fluorometil)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 3-{1 -[(2,2-difluorociclopropil)met¡l]-1 H-pirazol-4-il}-8-met¡l-2-(tr¡fluoromet¡l)-4Hpi rim ido[1,2-b]piridaz¡n-4-ona; 3-{1-[(3,3-d¡fluorociclobutil)metil]-1H-pirazol-4-¡l}-8-metoxi-2-(trifluorometil)-4Hp¡ rido[ 1,2-a]pirimidin-4-ona; 3-{1-[(3,3-d¡fluoroc¡clobut¡l)metil]-1H-pirazol-4-¡l}-8-metox¡-2-(tr¡fluoiOmetil)-4Hpirimido[1,2-b]piridaz¡n-4-ona; 3-{1 -[(3,3-difluoroc¡clobutil)met¡l]-1 H-pirazol-4-il}-8-met¡l-2-(trifluorometil)-4Hpirimido[1,2-b]piridaz¡n-4-ona; ficzQcn / zznz / q / υιλι 3-fluoro-1-metil-7-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-8-(trifluorometil)- H,2H,6H-[1,3]diazino[1,2-a]pirimidin-2,6-d¡ona; 4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2a]pirimidin-8-carbon¡tr¡lo; ácido 4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-il)-2-(trifluorometil)-4Hpirido[1,2-a]p¡r¡midin-8-carboxílico; 4-oxo-3-(4-(2,2,2-tr¡fluoroetoxi)fen¡l)-2-(tr¡fluorometil)-4H-pir¡do[1,2-a]pirimidin-8carbonitrilo; 4-oxo-3-(4-(2,2,2-tr¡fluoroetox¡)fen¡l)-2-(tr¡fluorometil)-4H-p¡r¡do[1,2-a]pirimidin-8carboxamida; ácido 4-oxo-3-(4-(2,2,2-trifluoroetox¡)fenil)-2-(trifluoromet¡l)-4H-pir¡do[1,2-a]p¡r¡m¡d¡n-8carboxílico; 4-oxo-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-il]-2-(trifluoromet¡l)-4H-pirido[1,2a]pirimid¡n-7-carbonitrilo; 7-(1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-il)-8-(tr¡fluorometil)-2H-pirimido[1,2a]pirimidin-2,6(1 H)-diona; 7-(3-fluoro-4-(2,2,2-trifluoroetox¡)fen¡l)-8-(trifluoromet¡l)-2H-p¡r¡mido[1,2-a]p¡nmid¡n- 2,6(1 H)-diona; 7-(4-(2,2,2-tr¡fluoroetox¡)fen¡l)-8-(trifluoromet¡l)-2H-pirimido[1,2-a]pirim¡din-2,6(1 H)diona; 7-(4-(2-fluoroetox¡)fen¡l)-8-(tr¡fluoromet¡l)-2H-pirim¡do[1,2-a]pirim¡din-2,6(1 H)-diona; 7-(metoximet¡l)-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l]-2-(trifluoromet¡l)-4Hpirido[1,2-a]pir¡m¡d¡n-4-ona; 7,8-dimetil-2-(trifluorometil)-3-[1-(3,3,3-trifluoropropil)-1 H-p¡razol-4-il]-4H-pirim¡do[1,2b]piridaz¡n-4-ona; 7,8-dimetil-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-¡l]-2-(tr¡fluorometil)-4Hpirim¡do[1,2-b]piridaz¡n-4-ona; 7,9-dimetil-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-¡l]-2-(tr¡fluoromet¡l)-4Hpirazino[1,2-a]pir¡m¡d¡n-4-ona; 7-chloro-2-(trifluoromet¡l)-3-[1 -(3,3,3-trifluoropropi I)-1 H-pirazol-4-yl]-4H-pi ridodo[1,2a]pyrim¡d¡n-4-one; 7-chloro-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-yl]-2-(tr¡fluoromethyl)-4Hpyrazino[1,2-a]pyrimid¡n-4-one; 7-chloro-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l]-2-(tr¡fluoromethyl)-4H-pyr¡do[1,2a]pyrim¡din-4-one; 7-chloro-8-methoxy-2-(trifluoromethyl)-3-[1 -(3,3,3-trifluoropropyl)-1 H-pyrazol-4-yl]-4Hpyrido[1,2-a]pyrim¡d¡n-4-ona; 7-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(trifluoromet¡l)-4H[1,3]diazino[1,2-a]pyrimidin-4-one; 7-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 Hp¡razol-4-yl]-2-(trifluoromet¡l)-4Hpyrido[1,2-a]pyr¡midin-4-one; 7-chloro-8-methyl-2-(trifluoromethyl)-3-[1 -(3,3,3-trifluoropropyl)-1 H-pyrazol-4-yl]-4H-pyrido[1,2a]pyrimid¡n-4-ona; 7-chloro-8-met¡l-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-¡l]-2-(tr¡fluoromet¡l)-4Hp¡rido[ 1,2-a]pyrim¡din-4-one; 7-chloro-8-met¡l-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2-a]pyrimidin4-ona; 7-cyclopropyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 7-cyclopropyl-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-¡l]-2-(trifluoromethyl)-4Hpirido[ 1,2-a]p¡r¡mid¡n-4-ona; 7-fluoro-2-(trifluoromethyl)-3-[1-(3,3,3-tr¡fluoropropyl)-1 H-pyrazol-4-yl]-4H-pyrido[1,2a]pyrim¡din-4-one; 7-fluoro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrim¡d¡n-4-ona; 7-fluoro-8-hidroxi-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(tnfluoromethyl)-4Hp¡ rido[ 1,2-a]pinm¡din-4-ona; 7-fluoro-8-methoxy-2-(trifluoroinet¡l)-3-[1-(3,3,3-tr¡fluoroprop¡l)-1H-pyrazol-4-yl]-4Hpyrido[1,2-a]pyrimid¡n-4-one; 7-fluoro-8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(tr¡fluorometil)-4H[1,3]diazino[1,2-a]pirimid¡n-4-ona; 7-fluoro-8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(trifluorometil)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 7-fluoro-8-metox¡-3-[4-(2,2,2-tr¡fluoroetoxi)fen¡l]-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2a]pirimidin-4-ona; 7-fluoro-8-metil-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(trifluorometil)-4Hp¡ rido[ 1,2-a]pirimidin-4-ona; 7-metoxi-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-il]-2-(tr¡fluorometil)-4H[1,3]diazino[1,2-a]pirimid¡n-4-ona; 7-metox¡-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-il]-2-(tr¡fluoromet¡l)-4Hpirazino[1,2-a]pinm¡din-4-ona; 7-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(trifl uorometil)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 7-methyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrimido[1,2b]pyridazin-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H[1,3]diazino[1,2-a]pyrimidin-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trfluoromethyl)-4Hpyrazino[1,2-a]pinimdin-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-¡l]-2-(trifluoromethyl)-4Hpyrimido[1,2-b]pyridazin-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-((1 R)-1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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-((1 S)-1-hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-((dimet¡lam¡no)met¡l)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-yl)-2(trifluoromet¡l)-4H-p¡r¡do[1,2-a]pyrimidin-4-one; 8-(methyloxa-d3)-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-((methylsulfanyl)methoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-((R)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-4-one; 8-((S)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-4-one; 8-(1,3-oxazol-2-yl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[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[1,2a]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)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(1-azetidinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(tr¡fluoromethyl)-4Hp¡rido[ 1,2-a]pyrim¡d¡n-4-one; 8-(chloromethoxyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethol)-4Hrido[1,2-a]pinimdin-4-one; 8-(chloromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrimido[1,2-b]pyridazyl-4-one; 8-(difluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(difluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 8-(dimethylamino)-3-(1-(2,2,3,3,3-pentafluoropropanol)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-(dimethylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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-trifluoropropanol)-1H-pyrazol-4-yl)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-(fluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrimido[1,2-b]pyridazin-4-one; 8-(fluoromethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pinimidine4-one; 8-(hydroxymethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[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)-4Hpyrido[1,2-a]pyramidal-4-one; 8-(methylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[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-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-paramido[1,2a]pyrimidin-4-one; 8-(methyl-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-p¡r¡do[1,2-a]p¡r¡ni¡d¡n-4one; 8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-¡l)-2-(tr¡fluoromet¡l)-4Hpyrim¡do[1,2-a]pinm¡din-4-one; 8-(methyloxl-d3)-3-(1-(4,4,4-trifluorobutyl)-1H[razol-4-l)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(methylox¡-d3)-3-(4-(2,2,2-trifluoroethoxy)phen¡l)-2-(trifluoromethyl)-4H-param¡do[1,2a]pyrim¡d¡n-4-one; 8-(met¡lox¡-d3)-3-(6-(2,2,2-tr¡fluoroethox¡)-3-pyr¡dinyl)-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2a]pyrimidin-4-one; 8-(methylsulfanyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-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)-4Hpyrido[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)-4Hpyrido[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-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-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]pyrimidine-4one; 8-cyclopropyl-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-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-hydroxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrimido[1,2-b]pyridazin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-imidazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrimido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]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-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrimido[1,2b]pyridazin-4-one; 8-methoxyl-2-(trifluoromethyl)-3-[3-(3,3,3-trifluoropropl)-1,2-oxazol-5-l]-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[4-(3,3,3-trifluoropropyl)-1H-imidazol-1-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,3-thiazol-2-yl]-4H-pyrido[1,2a]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)-1 Hpazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-¡l)-2-(tr¡fluoromet¡l)-4Hpyrimido[1,2-a]pyr¡m¡d¡n-4-one; 8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-1)-2-(trifluoromethyl)-4H-pyrimido[1,2a]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]pyrimidine-4-one; 8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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]paramidin-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)-2-(trifluoromethyl)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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-(2,2,2-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[1,2a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,3,3-tetrafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 8-methoxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-propenephenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyriminate; 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-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-paramido[1,2a]pyrimidin-4-one; 8-metoxi-3-(6-propil-3-pir¡dinil)-2-(tr¡fluoromet¡l)-4H-pirido[1,2-a]pirimidin-4-ona; 8-metoxi-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-1,2,3-tr¡azol-4-¡l]-2-(tr¡fluoromet¡l)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-3-¡l]-2-(tr¡fluorometil)-4Hpirido[1,2-a]pirimidin-4-ona; 8-metoxi-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-il]-2-(tr¡fluoromet¡l)-4H[1,3]diazino[1,6-a]pirimid¡n-4-ona; 8-metox¡-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-¡l]-2-(trifluoromet¡l)-4Hpirimido[1,2-b]piridaz¡n-4-ona; 8-metoxi-3-[2-(2,2,2-trifluoroetox¡)-1,3-tiazol-5-il]-2-(trifluorometil)-4H-pirido[1,2a]pirimid¡n-4-ona; 8-metoxi-3-[2-(2,2,2-tr¡fluoroetoxi)p¡r¡m¡d¡n-5-¡l]-2-(trifluoromet¡l)-4H-[1,3]diazirio[1,2a]pir¡mid¡n-4-ona; 8-metox¡-3-[2-(2,2,2-tr¡fluoroetox¡)p¡r¡m¡d¡n-5-¡l]-2-(tr¡fluoromet¡l)-4H-pirido[1,2a]pirimidin-4-ona; 8-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazin-4-one; 8-methoxy-3-[2-(2,2,3,3,3-pentafluoropropoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-Methoxy-3-[3-(2,2,3,3,3-pentafluoropropyl)-1,2-oxazol-5-yl]-2-(trifluoromethyl)-4Hprido[1,2-a]pyrimidine-4-one; ficzQcn / zznz / q / υιλι 8-methoxy-3-[4-(2,2,2-trifluoroethoxy)-1,3-triazol-2-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 8-methoxy-3-[5-(2,2,2-trifluoroethoxy)-1,3-tazol-2-yl]-2-(trifluoromethyl)-4H-parado[1,2a]pyrimidin-4-one; 8-methoxy-3-{1-[(oxetan-3-yl)methyl]-1H-pyrazol-4-¡l}-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 8-methoxy-6-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-methyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrimido[1,2b]pyridazin-4-one; 8-methyl-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,2,4-oxadiazol-3-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 8-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)4H,6H,7H,8H,9H-pyrimido[1,2-a]pyrazin-4-one; 8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-¡l]-2-(tr¡fluoromethyl)-4Hpyr¡mido[1,2-b]pyridaz¡n-4-one; 8-methyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazin-4-one; 8-methyl-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrimido[1,2-b]pyridazin-4-one; 9-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hrido[1,2-a]pyrimidine-4-one; 9-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 9-metil-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-il]-2-(trifluoromet¡l)-4Hpirazino[1,2-a]pirimidin-4-ona; 4-oxo-3-(4-(2,2,2-tr¡fluoroetoxi)fen¡l)-2-(trifluorometil)-4H-p¡r¡do[1,2-a]pirimidin-8carboxilato de metilo; fluoruro de metil(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l)-2(trifluoromet¡l)-4H-p¡r¡do[1,2-a]pirimidin-8-il)carbamilo; N-(4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4Hp¡r¡do[1,2-a]pirimidin-8-¡l)acetamida; N-(4-oxo-3-(4-(2,2,2-trifluoroetox¡)fen¡l)-2-(tr¡fluorometil)-4H-p¡r¡do[1,2-a]pirimidin-8il)acetamida; N,N-d¡met¡l-4-oxo-3-(4-(2,2,2-tr¡fluoroetox¡)fenil)-2-(tr¡fluoromet¡l)-4H-pirido[1,2a]pirimidin-8-carboxamida; N-etil-4-oxo-3-(4-(2,2,2-trifluoroetoxi)fen¡l)-2-(trifluoromet¡l)-4H-p¡r¡do[1,2-a]pirimidin-8carboxamida; N-methyl-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-8-carboxamide; either N-methyl-4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine8-carboxamide. 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-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-3-yl)phenoxy)propanenitrile; (2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3yl)phenoxy)propanenitrile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)-2methylpropanenitrile; 2-(difluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pinmidin-4-one; 2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pinimdin-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[1,2a]pyrimidin-4,8(1H)-dione; 3-(1-(2,2-difluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyramidal-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[1,2a]pyrimidine-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyramido[1,2a]pyrimidan-4-one; 3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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-d¡fluoroethoxy¡)-2-fluorophenyl)-8-methoxy¡-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyr¡m¡d¡n4-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; 3-(4-(cicloprop¡lmetox¡)fenil)-8-metox¡-2-(trifluorometil)-4H-p¡r¡do[1,2-a]pirim¡d¡n-4-ona; 4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(trifluoromet¡l)-4H-p¡r¡do[1,2a]pirimidin-8-carbon¡tr¡lo; 4-oxo-3-(4-(2,2,2-trifluoroetoxi)fen¡l)-2-(trifluorometil)-4H-pir¡do[1,2-a]pirimid¡n-8carboxamida; 7-(1 -(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-i l )-8-(trifl uorometil )-2H-pi rim ido[1,2a]pirimid¡n-2,6(1 H)-diona; 7-cloro-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-il]-2-(trifluorometil)-4H-pir¡do[1,2a]p¡rimidin-4-ona; 7-cloro-8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-¡l]-2-(trifluoromet¡l)-4H[1,3]diazino[1,2-a]pirimid¡n-4-ona; 7-fluoro-8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-¡l]-2-(tr¡fluorometil)-4Hp¡ rido[ 1,2-a]pir¡m¡d¡n-4-ona; 8-((1R)-1-hidroxiet¡l)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1 H-pyrazol-4-¡l)-2-(tr¡fluoromet¡l)4H-pyrido[1,2-a]pir¡m¡d¡n-4-ona; 8-((1S)-1-hidroxyethyl)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1 Hp¡razol-4-¡l)-2-(trifluoromet¡l)4H-pyrido[1,2-a]p¡r¡m¡din-4-ona; 8-((d¡metilamino)met¡l)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2(trifluorometil)-4H-pyrido[1,2-a]pyrimidin-4-one; 8-(aminomet¡l)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4Hpyrido[1,2-a]pirim¡d¡n-4-ona; 8-(dimet¡lam¡no)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-yl)-2-(tr¡fluoromet¡l)-4Hpyrido[1,2-a]pirim¡d¡n-4-ona; 8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hp¡ rido[ 1,2-a]pyrimidin-4-ona; 8-(fluoromethyl)-3-(4-(2,2,2-trifluoroethox¡)fen¡l)-2-(trifluoromethyl)-4H-p¡r¡do[1,2-a]pyrimidin4-ona; 8-(hidrox¡met¡l)-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-¡l)-2-(trifluoromet¡l)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 8-(hidroximetil)-3-(4-(2,2,2-trifluoroetoxi)fenil)-2-(trifluorometil)-4H-pirido[1,2-a]pirimidin4-ona; 8-(metoximet¡l)-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l]-2-(trifluoromet¡l)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 8-(metilamino)-3-(1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il)-2-(trifluoromet¡l)-4Hpirido[1,2-a]pir¡midin-4-ona; 8-(metilam¡no)-3-(4-(2,2,2-trifluoroetox¡)fenil)-2-(trifluoromet¡l)-4H-p¡r¡do[1,2-a]pirimidin4-ona; 8-(met¡lox¡-d3)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-¡l)-2-(tr¡fluoromet¡l)-4Hp¡ rido[ 1,2-a]pirim¡din-4-ona; 8-(metilox¡-d3)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(trifluoromet¡l)-4Hpi rim ido[1,2-a]pirimidin-4-ona; 8-(metiloxi-d3)-3-(4-(2,2,2-trifluoroetoxi)fenil)-2-(trifluorometil)-4H-p¡r¡do[1,2-a]pirimidin4-ona; 8-(methylox¡-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[1,2a]pyrimidin-4-one; 8-amino-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[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-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-paramido[1,2-a]pyrimidin-4one; 8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-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[1,2a]pyrimidine-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-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-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-paramido[1,2-a]paramido-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)-4Hrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-¡l]-2-(tr¡fluoromethyl)-4Hpyrimido[1,2-b]pyridaz¡n-4-ona; 8-methox¡-3-[2-(2,2,2-tr¡fluoroethox¡)p¡r¡m¡din-5-¡l]-2-(tr¡fluoromet¡l)-4H-pyrido[1,2a]pirimid¡n-4-ona; or 8-methoxy-3-[2-(2,2,2-tr¡fluoroethoxy)pyrimidin-5-¡l]-2-(trifluoromet¡l)-4H-p¡riinido[1,2b]pyridazin-4-one. In the present case the compound of acuerdo is proposed as Realization 92 with Realization 1, or a tautómero de este, or a pharmaceutically acceptable sal of that compound or of that tautómero, from which the compuesto is 4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromethyl)-4H-p¡r¡do[1,2a]pir¡m¡d¡n-8-carbon¡trilo; 8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromethyl)-4Hp¡rido[ 1,2-a]pihm¡d¡n-4-ona; 8-am¡no-3-(4-(2,2,2-tr¡fluoroethox¡)fen¡l)-2-(trifluoromet¡l)-4H-p¡r¡do[1,2-a]p¡hm¡d¡n-4-ona; 8-methoxy¡-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-¡l)-2-(trifluoromethyl)-4Hpyrido[1,2-a]p¡nmidín-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrimido[1,2-a]pyrimidin-4-one; either 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. 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 Provided herein as Embodiment 95 is the compound according to the Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is Provided herein as Embodiment 96 is the compound according to the Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is Provided herein as Embodiment 97 is the compound according to the Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is Provided herein as Embodiment 98 is the compound according to the Embodiment 1, or a pharmaceutically acceptable salt thereof, wherein the compound is The above merely summarizes certain aspects of this disclosure and is not intended to be, nor should it be considered to limit the disclosure in any way. ficzQcn / zznz / q / υιλι FORMULATION AND ROUTE OF ADMINISTRATION Although it may be possible to administer a compound disclosed herein only in the described uses, the administered compound will typically 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, 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. Alien Jr., Philadelphia, PA: Pharmaceutical Press, 2012; “Pharmaceutical Dosage Forms” (Volumes 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, Washington, 2000; “Pharmaceutical Formulation: The Science and Technology of Dosage Forms (Drug Discovery)”, First Edition, edited by G.D. Tovey, Royal Society of Chemistry, 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 that route and in a dosage effective for the intended treatment. The compounds and compositions presented herein may, for example, be administered orally, mucosally, topically, transdermally, rectally, pulmonary, parenterally, intranasally, intravascularly, intravenously, intraarterially, intraperitoneally, intrathecally, subcutaneously, sublingually, intramuscularly, intrasternally, 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, mini-tablet, caplet, lozenge, pellet, hard capsule, soft capsule, gelatin capsule, granule, powder, lozenge, patch, cream, gel, sachet, microsyringe set, syrup, flavored syrup, juice, candy, injectable solution, emulsion, microemulsion, ointment, aerosol, aqueous suspension, or oily suspension. The pharmaceutical composition is typically manufactured in the form of a dosage unit containing a particular quantity 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. Furthermore, this disclosure encompasses pharmaceutical compositions comprising mixtures of any of the compounds disclosed herein and one or more other active agents disclosed herein. METHODS OF USE As set forth herein (see the section entitled “Definitions”), the compounds described herein are to be understood to include all stereoisomers, tautomers, or pharmaceutically 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 present disclosure is to be understood to encompass methods and uses employing all such forms. In addition to being useful for treating humans, the compounds provided herein may be useful for the 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 the 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 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 the treatment of 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 the treatment of 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 the treatment of 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 the treatment of obesity. 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 the treatment of 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 the treatment of 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 body weight or 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 disorder 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 non-alcoholic steatohepatitis (NASH). Provided herein as Embodiment 112 is a method of reducing body weight or 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 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 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Provided herein as a further embodiment is the 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 the compound according to any one of Embodiment 198, 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 by 10% or more. In some embodiments, the method lowers blood glucose by 15% or more. In some embodiments, the method lowers blood glucose by 20% or more. In some embodiments, the method lowers blood glucose by 25% or more. In some embodiments, the method lowers blood glucose while exerting a minimal effect on food intake / appetite. In some embodiments, the method lowers blood glucose without exerting any effect on food intake / appetite. Rczocn / zznz / q / υιλι Provided herein as a further embodiment is a method of reducing insulin in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiment 198, 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 reduces insulin by 50% or more. In some embodiments, the method reduces insulin by 60% or more. In some embodiments, the method reduces insulin by 70% or more. In some embodiments, the method reduces insulin by 80% or more. In some embodiments, the method reduces insulinemia by 85% or more. In some embodiments, the method reduces insulin by 86% or more. In some embodiments, the method reduces insulin by 87% or more. In some embodiments, the method reduces insulin by 88% or more.In some embodiments, the method reduces insulin by 89% or more. In some embodiments, the method reduces insulin by 90% or more. In some embodiments, the method reduces insulin by 91% or more. In some embodiments, the method reduces insulin with minimal effect on food intake / appetite. In some embodiments, the method reduces insulin without having any 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 Embodiment 198, 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 by 10% or more. In some embodiments, the method lowers cholesterol by 15% or more. In some embodiments, the method lowers cholesterol by 20% or more. In some embodiments, the method lowers cholesterol by 30% or more. In some embodiments, the method lowers cholesterol by 31% or more. In some embodiments, the method lowers cholesterol by 32% or more. In some embodiments, the method lowers cholesterol by 33% or more.In some embodiments, the method reduces cholesterol by 34% or more. In some embodiments, the method reduces cholesterol by 35% or more. In some embodiments, the method reduces cholesterol levels by 36% or more. In some embodiments, the method reduces cholesterol by 37% or more. In some embodiments, the method reduces cholesterol by 38% or more. In some embodiments, the method reduces cholesterol by 39% or more. In some embodiments, the method reduces cholesterol while having a minimal effect on food intake / appetite. In some embodiments, the method reduces cholesterol without having any 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 Embodiment 198, 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 reduces low-density lipoproteins (LDL) by 10% or more. In some embodiments, the method reduces LDL by 20% or more. In some embodiments, the method reduces LDL by 21% or more. In some embodiments, the method reduces LDL by 22% or more. In some embodiments, the method reduces LDL by 23% or more. In some embodiments, the method reduces LDL by 24% or more. In some embodiments, the method reduces LDL by 25% or more. In some embodiments, the method reduces LDL by 26% or more.In some embodiments, the method reduces LDL in the blood by 27% or more. In some embodiments, the method reduces LDL with minimal effect on food intake / appetite. In some embodiments, the method reduces LDL without having any effect on food intake / appetite. Provided herein as a further embodiment is a method of reducing 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 reduces triglycerides by 30% or more. In some embodiments, the method reduces triglycerides by 40% or more. In some embodiments, the method reduces triglycerides by 50% or more. In some embodiments, the method reduces triglycerides by 51% or more. In some embodiments, the method reduces triglycerides by 52% or more. In some embodiments, the method reduces triglycerides by 53% or more. In some embodiments, the method reduces triglycerides by 54% or more.In some embodiments, the method reduces triglycerides by 55% or more. In some embodiments, the method reduces triglycerides by 56% or more. In some embodiments, the method reduces triglycerides by 57% or more. In some embodiments, the method reduces triglycerides with minimal effect on food intake / appetite. In some embodiments, the method reduces triglycerides without having any effect on food intake / appetite. Provided herein as a further embodiment is a method of reducing 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 reduces the fat mass of a subject by 30% or more. In some embodiments, the method reduces the fat mass of a subject by 40% or more. In some embodiments, the method reduces the fat mass of a subject by 45% or more. In some embodiments, the method reduces the fat mass of a subject by 50% or more. In some embodiments, the method reduces the blood fat mass of a subject by 60% or more.In some embodiments, the method reduces a subject's fat mass by 65% or more. In some embodiments, the method reduces a subject's fat mass by 70% or more. In some embodiments, the method reduces a subject's fat mass by 75% or more. In some embodiments, the method reduces a subject's fat mass while exerting a minimal effect on food intake / appetite. In some embodiments, the method reduces a subject's fat mass without exerting any effect on food intake / appetite. Provided herein as a further embodiment is a method of increasing adiponectin in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of the 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 198, 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 reducing resistin in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound according to any one of Embodiment 198, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to Embodiment 99. COMBINATIONS Provided herein 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 nonalcoholic 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 Embodiment 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. 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 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. 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 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. 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 the waist-to-hip ratio (WHR) 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. 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 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 reducing 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 1-98, 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 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 reducing 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 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 reducing 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 increasing 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 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 reducing 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 reducing resistin 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 of the combinations described herein or methods using 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 The following definitions are provided to facilitate understanding of the scope of this disclosure. Unless otherwise indicated, all numbers expressing quantities of ingredients, reaction conditions, etc., used in the specification and claims are to be understood as if modified in all instances by the term "about." Accordingly, unless otherwise indicated, the numerical parameters set forth in the following specification and appended claims are approximations that may vary depending on the standard deviation found in their respective test measurements. As used herein, if any variable appears more than once in a chemical formula, its definition in each instance is independent of its definition in any other instance. If the chemical structure and the chemical name contradict each other, the chemical structure is decisive for 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 hindered rotation, and therefore may exist as stereoisomers, such as double bond isomers (i.e., geometrical isomers (EIZ)), enantiomers, diastereomers, and atropisomers. Accordingly, it is to be understood that the scope of the present disclosure encompasses all possible stereoisomers of the exemplified compounds, including stereoisomerically pure forms (e.g., geometrically pure, enantiomerically pure, diastereomerically pure, and atropisomerically pure) and stereoisomeric mixtures (e.g., mixtures of geometrical isomers, enantiomers, diastereomers, and atropisomers, or mixtures of any of the foregoing) of any of the chemical structures disclosed herein (in whole or in part), unless the stereochemistry is specifically identified. If the stereochemistry of a structure or portion of a structure is not indicated by, for example, bold or dashed lines, the structure or portion of the structure should be interpreted as encompassing all stereoisomers within it. If the stereochemistry of a structure or portion of a structure is indicated by, for example, bold or dashed lines, the structure or portion of the structure should be interpreted as encompassing only the indicated stereoisomer. A bond represented by a wavy line indicates that both stereoisomers are encompassed. This should not 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 a stereoisomer (e.g., geometric isomer, enantiomer, diastereomer, and atropisomer) 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 enantiomer that is the mirror image 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 less than or equal to about 20% by weight of other stereoisomers of the compound, greater than about 90% by weight of one stereoisomer of the compound and less than or equal to about 10% by weight of the other stereoisomers of the compound, greater than about 95% by weight of one stereoisomer of the compound and less than or equal to 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 less than or equal to about 3% by weight of the other stereoisomers of the compound. This disclosure also encompasses pharmaceutical compositions comprising stereoisomerically pure forms and the use of stereoisomerically pure forms of any compounds disclosed herein. In addition, this disclosure also encompasses pharmaceutical compositions comprising mixtures of stereoisomers of any compounds disclosed herein and the use of such pharmaceutical compositions or mixtures of stereoisomers. These stereoisomers or mixtures thereof can be synthesized according to methods well known in the art and methods disclosed herein. Mixtures of stereoisomers can be resolved using standard techniques, such as chiral columns or chiral resolving agents. See, e.g., Jacques et al., “Enantiomers, Racemates and Resolutions” (Wiley-Interscience, New York, 1981); Wilen et al., 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 NotreDame Press, Notre Dame, IN, 1972). TAUTOMERS As those skilled in the art know, certain compounds disclosed herein may exist in one or more tautomeric forms. Because only one chemical structure can be used to represent a tautomeric form, reference to a compound of a given structural formula will be understood, for convenience, to include other tautomers of that structural formula. For example, the following is illustrative of tautomers of the compounds of Formula I, where w, y, and z are CRW, CRy, and CRZ, respectively, and x is COH: RzO RzO Accordingly, it should be understood that the scope of the present description encompasses all tautomeric forms of the compounds disclosed herein. ISOTOPICALLY LABELED COMPOUNDS Furthermore, the scope of the present disclosure includes all pharmaceutically acceptable isotopically labeled compounds of the compounds disclosed herein, such as compounds of Formula I, wherein one or more atoms have been replaced by atoms having the same atomic number, but a different atomic mass or mass number than the atomic mass or mass number typically 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 11C, 13C, and 14C, chlorine, such as 36Cl, fluorine, such as 18F, iodine, such as 123I and 125I, nitrogen, such as 13N and 15N, oxygen, such as 15O, 17O, and 18O, phosphorus, such as 32P, and sulfur, such as 35S. Certain isotopically labeled compounds of Formula I, for example, those incorporating a radioactive isotope, are useful in studies of drug and / or substrate tissue distribution.The radioactive isotopes tritium (3H) and carbon-14 (14C) are particularly useful for this purpose in view of their ease of incorporation and simple means of detection. Substitution with isotopes such as deuterium (2H or D) may provide certain therapeutic advantages resulting from increased metabolic stability, for example, an increase in in vivo half-life or reduced dosage requirements, and may therefore be advantageous in some circumstances. Substitution with positron-emitting isotopes, such as 11C, 18F, 15O, and 13N, may be useful in positron emission tomography (PET) studies, for example, to examine target occupancy.Isotopically labeled compounds of the compounds disclosed herein can generally be prepared using 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 labeled reagent in place of the unlabeled reagent previously employed. SOLVATES As set forth above, the compounds disclosed herein and stereoisomers, tautomers, isotopically labeled 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 present disclosure is to be understood to encompass all solvents for the compounds disclosed herein and stereoisomers, tautomers, and isotopically labeled forms thereof or a pharmaceutically acceptable salt of any of the foregoing. VARIOUS DEFINITIONS This section will define additional terms used to describe the scope of the compounds, compositions and uses disclosed herein. The terms “C1-3 alkyl”, “Cm alkyl”, “C2-6 alkyl” and “C1-6 alkyl” as used herein refer to a straight or branched chain hydrocarbon containing 1 to 3, 1 to 4, 2 to 6 and 1 to 6 carbon atoms, respectively. Representative examples of C1-3 alkyl, Cm alkyl, C2-6 alkyl or Cm alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, fert-butyl, pentyl and hexyl. The term “C2-4 alkenyl” as used herein refers to a saturated hydrocarbon containing 2 to 4 carbon atoms that has at least one carbon-carbon double bond. Alkenyl groups include both straight and branched moieties. Representative examples of C2-4 alkenyl include, but are not limited to, 1-propenyl, 2-propenyl, 2-methyl-2-propenyl, and butenyl. The terms “(C1-6 alkyl)amino” or “(C1-6 alkyl)amino” as used herein refer to -NHR*, where R* represents C1.4 alkyl and C1.6 alkyl, respectively, as defined herein. Representative examples of (C1-6 alkyl)amino or (C1-6 alkyl)amino include, but are not limited to, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3 and -NHCH(CH3)2. The term “C3-5 cycloalkyl” as used herein refers to a saturated carbocyclic molecule where the cyclic structure has 3 to 6 carbon atoms. Representative examples of C3-5 cycloalkyl 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 replaced by deuterium (“D”, “d”, or “H”). For example, the term “Cm deuteroalkyl” refers to a Cm alkyl as defined herein wherein one or more hydrogen atoms are replaced by D. Representative examples of Cm deuteroalkyl include, but are not limited to, -CH, -CHD, -CD, -CHCD, -CDHCD, -CDCD, -CH(CD), -CD(CHD), and -CH(CH)(CD). The terms “di(Ci-4 alkyl)amino” or “di(Ci-6 alkyl)amino” as used herein refer to -NR*R**, where R* and R** independently represent C-i4 alkyl and Cm alkyl, respectively, as defined herein. Representative examples of di(Ci-4 alkyl)amino or di(Ci-6 alkyl)amino 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 “Cm alkoxy” or “C1.3 alkoxy” as used herein refers to -OR#, where R# represents a Cm alkyl group or C1.3 alkyl group, respectively, as defined herein. Representative examples of Cm alkoxy or C1-3 alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, and butoxy. The term “halogen” as used herein refers to -F, -Cl, -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 replaced by a halogen as defined herein. The halogen is independently selected in each occurrence. For example, the term “C1-4haloalkyl” refers to a C1-4alkyl as defined herein, wherein one or more hydrogen atoms are replaced by a halogen. Representative examples of C1-4haloalkyl include, but are not limited to, -CH2F, -CHF2, -CF3, -CHFCI, -CH2CF3, -CFHCF3, -CF2CF3, -CH(CF3)2, CF(CHF2)2, and -CH(CH2F)(CF3). The term “5-membered heteroaryl” as used herein refers to a 5-membered carbon ring with two double bonds containing a ring heteroatom selected from N, S, and O, and optionally one or two additional ring N atoms in place of the one or more ring carbon atoms. Representative examples of a 5-membered heteroaryl include, but are not limited to, furyl, imidazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, and oxazolyl. The term “CW heterocycloalkyl” or “C3Y heterocycloalkyl” as used herein refers to a saturated carbocyclic molecule where the cyclic structure has 3 to 5 carbons or 3 to 4 carbons and where one carbon atom is replaced by a heteroatom selected from N, O and S. Representative examples of C3 heterocycloalkyl or C3-4 heterocycloalkyl include, but are not limited to, aziridinyl, azetidinyl, oxetanyl and pyrrolidinyl. The term “pharmaceutically acceptable” as used herein refers to something that is generally accepted for use in subjects, particularly humans. The 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, melic 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 parent compound 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. Examples can be found. Additional references to such salts are in Berge et al., J. Pharm. Sci. 66(1 ):1–19 (1977). See also Stahl et al., “Pharmaceutical Salts: Properties, Selection, and Use,” 2nd Revised Edition (2011). The term “pharmaceutically acceptable excipient” as used herein refers to a wide range of ingredients that can be combined with a compound or salt disclosed herein to prepare a pharmaceutical formulation or composition. Typically, excipients include, but are not limited to, diluents, colorants, carriers, anti-adherents, 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 in a tissue, system, or subject expected by a researcher, veterinarian, physician, or other practitioner. 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 their height in meters. See, e.g., https: / / www.cdc.gov / healthyweight / assessing / bmi / index.html (last accessed November 4, 2019). BMI is an indicator of the amount of body fat in a subject, such as a human. BMI is used as a screening tool to identify whether a subject is at a healthy weight or responding to weight-loss treatment. SYNTHESIS PROCEDURES The compounds provided herein can be synthesized according to the procedures described in this section and in the following sections. The synthetic methods described herein are merely exemplary, and the compounds disclosed herein can also be synthesized by alternative routes using alternative synthetic strategies, as will be appreciated by those skilled in the art. It should be appreciated that the general synthetic procedures and specific examples provided herein are merely illustrative and should not be construed as limiting the scope of the present disclosure in any way. All starting materials are available, for example, from Sigma-Aldrich Chemical Company, Inc., St. Louis, MO, USA, or are known in the art and can be synthesized using known methods using ordinary skill. The starting material can also be synthesized by the methods disclosed herein. ficzQcn / zznz / q / υιλι As the skilled artisan can appreciate, the representative examples are not intended to constitute an exhaustive list of all means by which the compounds described and claimed in this application can be synthesized. Other methods will be apparent to those skilled in the art. Additionally, the various synthetic steps described above can be performed in an alternative sequence or order to obtain the desired compounds. Purification methods for the compounds described herein are known in the art and include, for example, crystallization, chromatography (e.g., liquid and gas phase), extraction, distillation, disaggregation washing, and reverse-phase HPLC. The disclosure also encompasses "intermediate" compounds, which include structures produced from the described synthetic procedures, whether isolated or generated in situ and without isolation, prior to obtaining the desired compound. These intermediates are included within 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-(trifluoromethyl)-4H-pyr¡do[1,2-a]pyrm¡d¡n-8-¡l)acetamide; 8-bromo-3-iodo-2-(trifluoromethyl)-4H-pyr¡do[1,2-a]pinm¡din-4-one; 8-bromo-2-(tnfluoromet·l)-4H-pindo[1,2-a]pyrimid·n-4-ona; 8-hydroxy-2-(trifluorometl)-4H-pirido[1,2-a]piramidin-4-ona; 4-oxo-2-(tr·fluoromethyl)-4H-p·hdo[1,2-a]p·r·mid·n-8-carbon·tnlo; 3-Iodo-4-oxo-2-(tr¡fluoromethyl)-4H-p¡ndo[1,2-a]pirim¡d¡n-8-carbonitr¡lo; 3-bromo-8-metox·2-(tr·fluoromethyl)p·r·m·do[1,2-a]p·r·m·d·n-4-ona; 8-metox·2-(tr·fluoromethyl)-4H-p·nm·do[1,2-a]pyrimid·n-4-ona; oh 1-(2,2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pirazol. EJEMPLOS This section provides specific examples of Formula I compounds and methods for preparing them. LIST OF ABBREVIATURAS TABLE 1 AcOH Acid AIBN Azobisobutironitrile ac o aq. BOC o Boc Ferf-butyloxicarbonil Cu(OTf)2 Trifluorometanosulfonate Cobalt Cy Cyclohexano ficzQcn / zznz / q / υιλι DAST Diethylaminosulfur trifluoride DCE 1,2-dichloroethane DABCO 1,4-diazabicyclo[2.2.2]octane DIBAL-H Diisobutylaluminum hydride DCM dichloromethane DIAD Diisopropyl azodiformate DMA Λ,ΔN-dimethylacetamide DMAP 4-dimethylaminopyridine DME 1,2-dimethoxyethane DMF N,N-dimethylformate DMSO dimethyl sulfoxide DMP Dess-Martin periodinane Dppf, DPPF or dppf 1,1'-bis(d-phenylphosphino)ferrocene eq or eq. or equiv.equivalent ESI or ES electrospray ionization Et ethyl Et2O diethyl ether EtOAc ethyl acetate g gram(s) h hour(s) HATU (1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5b]pyridinium 3-oxide hexafluorophosphate HBTU N,N,N',N'-Tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate, O-(benzothazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate HPLC high pressure liquid chromatography ¡Pr isopropyl ¡Pr2NEt or DIPEA N-Ethyldiisopropylamine (Hünig's base) KHMDS potassium hexamethyldisilazide KOAc potassium acetate LC MS, LCMS, LC-MS or LC / MS liquid chromatography with mass spectroscopy LG leaving group (e.g., halogen, mesylate, triflate) LHMDS or LiHMDS lithium hexamethyldisilazide. Rczocn / zznz / q / υιλι m / z mass divided by charge mCPBA meta-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 mi milliliters MS mass spectra NaHMDS sodium hexamethyldisilazide NBS N-bromosuccinimide n-BuL¡ n-butyllithium NIS N-iodosuccinimide NBS N-bromosuccinimide NCS N-chlorosuccinimide NMP A / -Methyl-2-pyrrolidone NMR nuclear magnetic resonance Pd-118, Pd(dtbpf)Cl2 1,1'-bis(di-tert-butylphosphino)ferrocene]dichloropalladium(II) dichloride Pd2(dba)s tns(dibenzylideneacetone)dipalladium(0) Pd(dppf)CI2 [1 ,T-bis(diphenylphosphino)phenocene]-dichloropalladium(ll) Pd(dppf)CI2-DCM [1 ,r-bis(diphenylphosphino)ferrocene]-dichloropalladium(ll), complex with dichloromethane Pd(PPh3)4 tetraquis(triphenylphosphine)palladium(0) Ph phenyl PPA Polyphosphoric acid PR or PG or Prot. group.protecting group mfr round bottom flask RP HPLC reversed phase high pressure liquid chromatography RT or RT or RT room temperature. sat. or satd. saturated SCX strong cation exchange SFC supercritical fluid chromatography SIPr 1,3-Bis(2,6-diisopropylphenyl)imidazolidene SPhos 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl SPhos Palladacyclo or SPhos Palladacyclo G1 Adduct of t-butyl methyl ether and (2-dicyclohexylphosphino-2',6'-dimethoxy-1,1'-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) chloride Sphos Palladacyclo G3 (2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate TBAF tetra-n-butylammonium fluoride TBTU tetrafluoride gold borate N,N,N',N'-tetramethyl-O(benzotriazol-1-yl)uronío tBuBrettPhos Paladacyclo G3 Methanesulfonato(2-(di-t-butylphosphino)-3,6-dímethoxy2',4',6'-tri-i-propíl-1,1 '-biphen i I )(2'-am in o-1,1 '-biphen i I-2yl)palladium(ll) t-BuOH tert-butanol TEA or Et3N Trimethylamine TFA trifluoroacetic acid THF tetrahydrofuran UV ultraviolet XantPhos 4,5-Bis(diphenylphosphine)-9,9-dimethylxanthene GENERAL ANALYTICAL AND PURIFICATION METHODS This section provides descriptions of the general analytical and purification methods used to prepare the specific compounds provided herein. Chromatography: Unless otherwise noted, residues containing crude product were purified by passing the crude material or concentrate through either a Biotage or Isco brand silica gel column (prepacked or individually packed with SI02) or reversed phase (C18) fast silica and eluting the product from the column with a solvent gradient as indicated. For example, a description of (330 g SiO2, 0-40% EtOAc / hexane) means that the product was obtained by elution from the column packed with 330 grams of silica, with a solvent gradient of 0% to 40% EtOAc in hexanes. Preparative HPLC method: Where indicated, the compounds described herein were purified by reversed-phase HPLC using one of the following instruments: Shimadzu, Varian, Gilson, Agilent 1260 infinity, or Waters Fractionlynx; using one of the following HPLC columns: (a) a 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 run through the instrument included eluting at 45 ml / min with a linear gradient from 10% (v / v) to 100% MeCN (0.1% v / v TFA) in water (0.1% TFA) over 10 minutes; conditions could be varied to achieve optimal separations. Proton NMR spectra: Unless otherwise indicated, all 1H NMR spectra were obtained on a Bruker NMR instrument at 300 or 400 or 500 MHz. When so characterized, all observed protons are reported as parts per million (ppm) in decreasing fields relative to 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), with a molecular ion (M+H+). The reported molecular ion was obtained by electrospray detection (commonly referred to as ESI MS) using 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 isotopic pattern detected, as will be appreciated by those skilled in the art. Names of compounds The compounds disclosed and described herein have been named using the IUPAC naming convention provided with ChemDraw Professional 15.1.0.144 software, ACD / Labs, version 2015 software, from Advanced Chemistry Development Inc., or with JChem for Excel 18.22.1.7 from ChemAxon Ltd. SPECIFIC EXAMPLES This section provides procedures for synthesizing specific examples of the compounds provided herein. All starting materials are either available from the commercial supplier Sigma-Aldrich Chemical Company, Inc., St. Louis, MO, USA, unless otherwise indicated, or are known in the art and can be synthesized using known procedures using conventional techniques. Synthesis of intermediates: INTERMEDIATE 1-A 3-BROMO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE Step 1 Step 2 STEP 1: 8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-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 at 100 °C for 5 h. 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[1,2-a]pyrimidin-4-one (2.16 g, 8.9 mmol, 28% yield). LC / MS (ESI+) m / z = 245.2 [M+H]+. STEP 2: 3-BROMO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1.2-A1PYRIMIDIN-4-ONE· A solution of bromine (8 μI, 0.16 mmol) in acetic acid (0.5 mL) was added dropwise to a solution of 8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (40 mg, 0.16 mmol) in acetic acid (1.2 mL) at rt. After the addition was complete, 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 material was purified by silica gel chromatography (eluent: 5-50% EtOAc / heptane) to afford 3-bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (52 mg g, 0.16 mmol, 98% yield) as a white solid. MS (EST) m / z = 323.0 [M+H] + .1H NMR (400 MHz, CDCl3) δ 8.97 (d, J=7.82 Hz, 1H) 7.05 (d, J=2.74 Hz, 11-1) 6.98 (dd, J=7.92, 2.64 Hz, 11-1) 4.02 (s, 3H). INTERMEDIATE 1-B 3-IODO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDON,2-A1PYRIMIDIN-4-ONE Step 1 Step 2 STEP 1: 8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE· The title compound was prepared using the procedure described for Intermediate 1-A, Step 1. STEP 2: 3-IODO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE· To a solution of 8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.22 g, 0.89 mmol) in acetonitrile (5 mL) was added N-iodosuccinimide (0.24 g, 1.1 mmol). The 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[1,2-a]pyrimidin-4-one (0.31 g, 0.84 mmol, 94% yield). LC / MS (ESI+) m / z = 370.9 [M+H]+, 371.9 [M+2H]+.1H NMR (400 MHz, CDCI3) δ 8.98 (d, J=7.82 Hz, 1H), 7.06 (d, J=2.74 Hz, 1H), 6.97 (dd, J=2.64, 7.92 Hz, 1H), 4.02 (s, 3H).19F NMR (376 MHz, CDCI3) δ -67.21 (s, 3F). INTERMEDIATE 1-C 3-BROMO-2-(DIFLUOROMETHYL)-8-METHOXYPYRIDON.2-A1PYRIMIDIN-4-ONES STEP 1: 2-(DIFLUOROMETHYL)-8-METHOXY-4H-PYRIDON.2-A1PYRIMIDIN-4-ONES; 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 at reflux for 18 h. The reaction mixture was concentrated under reduced pressure and then partitioned between CH2Cl2 (50 mL) and 5 M NaOH (20 mL). The organic layer was extracted with CH2Cl2 (2χ) and the combined organic layers were dried over Na2SO4. The filtrate was concentrated in vacuo. The crude residue was suspended in DCM (10 mL) and filtered. The filtrate was purified by silica gel chromatography (eluent: 0-35% (EtOAc / EtOH 3:1) / heptane) to afford 2-(difluoromethyl)-8-methoxy-4H-pyrido[1,2a]pyrimidine-4-one (0.92 g, 4.1 mmol, 14% yield) as a solid. 1H NMR (400 MHz, CDCl3) δ 8.95 (d, J=7.9 Hz, 1H), 6.97 (d, J=2.5 Hz, 1H), 6.88 (dd, J=7.9, 2.70 Hz, 1H), 6.54 (s, 1H), 6.43 (m, 1H), 3.99 (s, 3H). STEP 2: 3-BROMO-2-(DIFLUOROMETHYL)-8-METHOXYPYRIDOR.2-A1PYRIMIDIN-4-ONES; 1,3-Dibromo-5,5-dimethylhydantoin (0.81 g, 2.9 mmol) was added to a stirred suspension of 2-(difluoromethyl)-8-methoxy-4H-piño[1,2-a]piñondin-4-one (0.92 g, 4.1 mmol) in DMF (7 mL) / DCM (4 mL) at -45 °C under nitrogen. After 30 min, the reaction was treated with saturated aqueous NaHCO3 solution (20 mL) and EtOAc (25 mL), and after stirring for 15 min, the resulting precipitate was filtered off. The organic phase was separated from the filtrate, washed with brine (10 mL), and dried over Na2SO4. The filtrate was concentrated under reduced pressure. The crude material was suspended in DCM (5 mL). The solid was filtered off and dried to give 3-bromo-2-(difluoromethyl)-8-methoxy-4H-pyrido[1,2a]pyrimidine-4-one (0.73 g, 2.4 mmol, 59% yield) as a white solid. LC / MS (ESI+) m / z = 305.0 [M+H]+.1H NMR (400 MHz, CDCl3) δ 8.96 (d, J=7.88 Hz, 1H), 7.07-7.08 (m, 1H), 6.93 (t, J=52 Hz, 1H), 6.95 (d, J=2.7 Hz, 1H), 4.00 (s, 3H). INTERMEDIATE 1-D 3-IODO-4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDORI.2-A1PYRIMIDIN-8-CARBOXYLATE METHYL STEP 1: 4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDOf1,2-A1PYRIMIDIN-8-METHYL CARBOXYLATE. 8-Bromo-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one (10 g, 34 mmol, Intermediate 3-C), methanol (10 mL), DIPEA (30 mL, 171 mmol), and Pd(dppf)Cl2 (2.5 g, 3.1 mmol) were charged into a pressure autoclave. The reaction mixture was heated to 70 °C for 20 h under a carbon monoxide atmosphere (70 psi pressure). The reaction mixture was cooled to rt and filtered through a pad of celite. The celite pad was washed with dichloromethane (3 x 50 mL). The combined filtrate was concentrated under reduced pressure. The residue was dispersed in water (100 mL) and extracted with DCM (3 x 100 mL). The combined organic layers were washed with brine (50 mL), dried over Na2SO4, 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-pyrido[1,2-a]pyrimididine-8-carboxylate (6.7 g, 72% yield) as a pale yellow solid.LC / MS (ESP) m / z = 273.1. [Μ+Η]+.1Η NMR (400 ΜΗζ, DMSO-d6) δ 9.07 (d, J=7.4 Ηζ, 1Η), 8.20 (d, J=1.9 Ηζ, 1 Η), 7.73 (dd, J=7.2, 1.8 Ηζ, 1 Η), 7.00 (s, 1Η), 3.96 (s, 3Η). STEP 2: 3-IODO-4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1 .2-A1PYRIMIDINE-8CARBOXYLATE METHYL. The title compound was prepared using the procedure described for Intermediate 1-B, Step 2 with the following modification: Step 2 was performed with methyl 4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylate. LC / MS (ESI+) m / z = 398.9 [M+H]+. INTERMEDIATE 1-E 8-(DIMETHYLAMINO)-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDON,2-A1 PYRIMIDIN-4-ONE Intermediate 3-1 STEP 1: 8-(DIMETHYLAMINO)-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1 PYRIMIDIN4-ONE. 8-Bromo-3-iodo-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one (0.5 g, 1.2 mmol, Intermediate 3-I), DMF (5 mL), copper(I) iodide (52 mg, 0.28 mmol), and dimethylamine (0.66 mL, 1.3 mmol) were placed in a resealable vial under nitrogen. The reaction mixture was stirred at 80 °C for 3 h. 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-water (3 x 20 mL), dried over Na2SO4, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 25-30% ethyl acetate / hexane) to afford 8-(dimethylamino)-3-iodo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.32 g, 0.84 mmol, 70% yield) as a solid. LC / MS (ESI+) m / z = 384.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J=8.1 Hz, 1H), 7.20 (dd, J=8.2, 2.9 Hz, 1H), 6.66 (d, J=2.9 Hz, 1H), 3.19 (s, 6H). INTERMEDIATE 1-F 3-IODO-8-(METHYLAMINO)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1 PYRIMIDIN-4-ONE Intermediate 3-1 RASO 1: 3-IODO-8-(METHYLAMINO)-2-(TRIFLUOROMETHYL)-4H-PYRIDOI1,2-A1 PYRIMIDIN4ONE· The 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 (ESP) m / z = 370.2 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.67 (d, J=7.8 Hz, 1H), 8.04 (d, J=6.5 Hz, 1H), 6.96-6.84 (m, 1H), 6.48 (s, 1H), 2.87 (d, J=4.8 Hz, 3H). INTERMEDIATE 1-G 8-ACETYL-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE (1 )Tributyl(1-ethoxyvinyl)tin, Pd(PPh3)4, Toluene (2) HCI ---------► Step 1 3 Intermediate 3-I STEP 1: 8-ACETYL-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE· 8-Bromo-3-iodo-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one (2.5 g, 6.0 mmol, Intermediate 3-I), toluene (25 mL), and tributyl(1-ethoxyvinyl)stannane (2.2 g, 6.0 mmol) were charged into a pressure tube. The reaction mixture was purged with nitrogen for 10 min, after which Pd(PPh3)4 (0.69 g, 0.6 mmol) was added. The reaction mixture was heated to 105 °C for 1 h. The reaction mixture was cooled to rt and filtered through a pad of celite. The filtrate was concentrated under reduced pressure to give a crude residue, which was dissolved in acetone (35 mL). The solution was cooled to 0 °C and treated with 10% aqueous HCl solution (17 mL). The reaction mixture was warmed to rt and 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 (3 x 30 mL). The combined organic layers were dried over Na2SO4, and the filtrate was adsorbed onto a plug of silica gel.Purification by silica gel chromatography (eluent: 0-20% EtOAc / hexane) gave 8-acetyl-3-iodo2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (700 mg, 31% yield) as a yellow solid. LC / MS (ESP) m / z = 382.9 [M+H] + 1H NMR (400 MHz, DMSO-d6) δ 9.02 (d, J=7.5 Hz, 1H), 8.43 (d, J=1.9 Hz, 1H), 7.72 (dd, J=7.4, 2.0 Hz, 1H), 2.74 (s, 3H). INTERMEDIATE 1-H 3-IODO-4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-8-CARBONITRILE , Hasoi Paso / Intermediate 3 C STEP 1: 4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDOf1.2-A1PYRIMIDIN-8-CARBONITRILE· 8-Bromo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyridine-4-one (0.3 g, 1.0 mmol, Intermediate 3-C), zinc cyanide (0.12 g, 1.0 mmol), and Pd(PPh) (0.12 g, 0.10 mmol) were placed in a resealable vial. The vial was evacuated and filled with nitrogen. This procedure was repeated 3 times, after which NMP (5 mL) was added. The reaction mixture was heated to 90 °C. After 18 h, the reaction mixture was partitioned between EtOAc and water. The organic phase was washed with brine, dried over MgSO, filtered, and adsorbed onto a plug of silica gel. Purification by silica gel chromatography (eluent: 0-10% (EtOAc / EtOH 3:1) / heptane) gave 4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pnimide-8-carbonyl (0.16 g, 0.66 mmol, 64% yield) as a yellow solid. LC / MS (ESI+) m / z = 240.0 [M+H]+.1H NMR (CDCl3, 400 MHz) δ 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-(TRIFLUOROMETHYL)-4H-PYRIDO[1.2-A1PYRIMIDIN-8CARBONITRILE· 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-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimid¡dine-8-carbon¡trile. LC / MS (ESI*) m / z = 366.0 [M+H]+.1H NMR (400 MHz, CDCl3) δ 9.02 (d, J=7.4 Hz, 1H), 8.61 (d, J=1.8 Hz, 1H), 7.73 (dd, J=7.4, 1.9 Hz, 1H). INTERMEDIATE 1-1 7-CHLORINE-3-IODOINE-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE STEP 1: 7-CHLORO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1.2-A1PYRIMIDIN-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-methoxypyridin-2-amine (prepared according to the procedure described in WO2017 / 200825A1). LC / MS (ESP) m / z = 279.0 [M+H] + .1H NMR (400 MHz, DMSO-d6) δ 9.04 (1H, s) 7.47 (1H, s) 6.70 (1H, s) 4.13 (4H, s). STEP 2: 7-CHLORINE-3-IODINE-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDORi,2A1PYRIMIDIN-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 7-chloro-8-methoxy2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 405.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 9.03 (1H, s) 7.45 (1H, s) 4.13 (3H, s). Intermediate 1-J 2-(DIFLUOROMETHYL)-3-IODO-4-OXO-4H-PYRIDOri,2-A1PYRIMIDIN-8-CARBONITRILE STEP 1: 2-(DIFLUOROMETHYL)-4-OXO-4H-PYRIDOÍ1.2-A1PYRIMIDIN-8-CARBONITRILE· 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-aminoisonicotinonitrile and 4,4-difluoro-3-oxobutanoic acid ethyl ester (Combi-Blocks Inc). LC / MS (ESP) m / z = 222.1 [M+H] + .1H NMR (400 MHz, DMSO-d6) δ 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-(DIFLUOROMETHYL)-3-IODO-4-OXO-4H-PYRIDO[1.2-A1PYRIMIDIN-8CARBONITRILE· The title compound was prepared using the procedure described for Intermediate 1-B, Step 2 with the following modification: Step 2 was performed with 2-(difluoromethyl)4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carbonitrile. LC / MS (ESP) m / z = 348.1 [M+H] + .1H NMR (400 MHz, DMSO-d) δ 6.96 - 7.29 (t, 1H) 7.67 (dd, 1H) 8.58 (d, 1H) 9.00 (dd, 1H). Intermediate 1-K 3-IODO-8-(METHYLTIUM)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1 PYRIMIDIN-4-ONE Step 1 Step 2 STEP 1: 4-(METHYLTHIO)PYRIDIN-2-AMINE. Sodium thiomethoxide (65.4 g, 933 mmol, Chempure) was added to a solution of 4-chloropyridin-2-amine (20 g, 156 mmol, Combi-Blocks, Inc.) in water (300 mL) at rt. The reaction mixture was stirred at 100 °C for 2 d. 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 Na2SO4, 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 used in the next step without further purification. LC / MS (ESP) m / z = 141.1 [M+H]+.1H NMR Rczocn / zznz / q / υιλι (400 MHz, DMSO-de) δ 7.72 (d, J=5.5 Hz, 1H), 6.36 (dd, J=5.5, 1.7 Hz, 1H), 6.27 (d, J=1.7 Hz, 1H), 5.89 (s, 2H), 2.41 (s, 3H). STEP 2: 8-(METHYLTIUM)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-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 4-(methylthio)pyridin-2-amine. LC / MS (ESI+) m / z = 261.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.80 (dd, J=7.6, 1.4 Hz, 1H), 7.49 (d, J=2.1 Hz, 1H), 7.39 (dt, J=7.6, 1.8 Hz, 1H), 6.70 (d, J=1.4 Hz, 1H), 2.69 (d, J=1.6 Hz, 3H). STEP 3: 3-IODOINE-8-(METHYLTIUM)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1 PYRIMIDIN-4ONE. The title compound was prepared using the procedure described for Intermediate 1-B, Step 12 with the following modification: Step 2 was performed with 8-(methylthio)-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 386.9 [M+H]+.1H NMR (400 MHz, DMSO-dS) δ 8.79 (d, J=7.5 Hz, 1H), 7.48-7.40 (m, 2H), 2.69 (s, 3H). Intermediate 1-L N-(3-YODO-4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDOÍ1,2-A1PYRIMIDIN-8-IL)ACETAMIDA About H3CC(())NH7 Pd2(dba)3, Xantphos Cs2CO3, dioxane Step 1 Intermediate 3-I STEP 1: N-(3-YODO-4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDO-2,2-A1PYRIMIDIN-8YL)ACETAMIDE. Into a resealable vial was placed 8-bromo-3-iodo-2-(trifluoromethyl)-4H-pyrido[1,2a]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 min, after which Pd2(dba)3 (11 mg, 0.012 mmol) and Xantphos (7 mg, 0.012 mmol) were added. The reaction mixture was then heated to 80 °C for 5 h. The reaction mixture was cooled to room temperature and concentrated under reduced 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[1,2-a]pyrimidin-8yl)acetamide (0.035 g, 0.088 mmol, 37%) as a yellow solid. LC / MS (ESI+) m / z = 397.9 [M+H]+. INTERMEDIATE 1-Μ 3-IODO-8-ISOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDON.2-A1PYRIMIDIN-4-ONE Intermediate 3 C STEP 1: 8-ISOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDON.2-A1PYRIMIDIN-4-ONE· Isopropylmagnesium chloride (2M in THF, 4.3 mL, 8.5 mmol) was added dropwise to a solution of 8-bromo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (1.0 g, 3.4 mmol, Intermediate 3-C) and COCl2 (0.22 g, 1.7 mmol) in benzene (10 mL) at rt under nitrogen. The reaction mixture was stirred at 80 °C for 3 h. The reaction mixture was diluted with 1.5 N aq. 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. The crude material was purified by silica gel chromatography (eluent: 0-40% EtOAc / hexane) to afford 8-isopropyl-2-(trifluoromethyl)-4H-pyrido[1,2-a]piñomídin-4-one (350 mg, 40% yield) as an off-white solid. LC / MS (ESI+) m / z = 257.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.95 (dd, J=7.4, 3.2 Hz, 1H), 7.71 - 7.66 (m, 1H), 7.50 (dd, J=7.4,1.9 Hz, 1H), 6.74 (d, J=2.4 Hz, 1H), 3.10 (h, J=6.9 Hz, 1H), 1.28 (d, J=6.9 Hz, 6H). STEP 2: 3-IODOINE-8-ISOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4ONA· 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[1,2-a]pyrimidin-4-one. LC / MS (EST) m / z = 383.0 [M+H] + .1H NMR (400 MHz, DMSO-d6) δ 8.96 (dd, J=7.3, 2.8 Hz, 1H), 7.72 (d, J=2.0 Hz, 1H), 7.56 (dd, J=7.4, 2.0 Hz, 1H), 3.13 (p, J=6.8 Hz, 1H), 1.29 (d, J=6.9 Hz, 6H). INTERMEDIATE 1-N 3-BROMO-8-(METHOXY-D3)-2-(TRIFLUOROMETHYL)4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE Intermediate 1-Q STEP 1: 8-(METHOXY-D3)-2-(TRIFLUOROMETHYL)-4H-PYRIDori,2-A1PYRIMIDIN-4-ONE· Iodomethane-d3 (0.5 mL, 7.8 mmol) was added to a reaction mixture of 8-hydroxy-2-(trifluoromethyl)-4H-pyrido[1,2-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 1 h, the reaction mixture was diluted with water and EtOAc. The organic layer was separated, washed with water and brine, dried over Na2SO4, and concentrated in vacuo. The crude residue was purified by silica gel chromatography (eluent: 0-100% EtOAc / heptane) to afford 8-(methoxy-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as an off-white solid. LC / MS (ESI+) m / z = 248.0 [M+H]+.1H NMR (400 MHz, CDCl3) δ 6.61 (s, 1H) 6.91 (dd, J=7.88, 2.70 Hz, 1H) 7.04 (d, J=2.70 Hz, 1H) 8.96 (d, J=7.88 Hz, 1H). RASO 2: 3-BROMO-8-(METHOXY-D3)-2-(TRIFLUOROMETHYL)-4H-RIRIDOM,2-A1PYRIMIDIN-4ONE. 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[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 326 / 328 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.25 (dd, J=7.88, 2.70 Hz, 1H) 7.31 (d, J=2.70 Hz, 1H) 8.91 (d, J=7.88 Hz, 1H). INTERMEDIATE 1-0 3-BROMO-8-METHOXY-2-(TRIFLUOROMETHYL)PYRIMIDOn,2-A1PYRIMIDIN-4-ONE STEP 1-1 AND STEP 1-2: 3-BROMO-8-METHOXY-2-(TRIFLUOROMETHYL)PYRIMIDOri,2A1PYRIMIDIN-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 under 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 at rt for 1 h. The reaction mixture was concentrated in vacuo, and the residue was treated with water, sat. NaHCO3, and EtOAc. The organic layer was separated and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 0-50% EtOAc / heptane) to afford 3-bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one (1.0 g, 3.2 mmol, 7% yield). LC / MS (ESI+) m / z = 324.0 / 326.0 [M+H]+ 1H NMR (400 MHz, CDCl3) δ 9.07 (d, J=7.63 Hz, 1H), 6.82 (d, J=7.63 Hz, 1H), 4.23 (s, 3H). INTERMEDIATE 1-P 3-BROMINE-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE Step 1 Step 2 Steps 1 and 2 were performed according to the synthesis procedure described in WO2008097991. LC / MS (ESI+) m / z = 295.0 [M+H]+. INTERMEDIATE 1-Q 8-HYDROXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE STEP 1: 8-HYDROXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-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 (ESI+) m / z = 231.0 [M+H]+. INTERMEDIATE 1-R 3-BROMINE-8-(METHOXY-D3)-2-(TRIFLUOROMETHYL)-4H-PYRIMIDORi.2-A1PYRIMIDIN-4-ONE Step 1 Step 2 EITHER Step 3 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 min, and a solution of 2-amino-4-chloropyrimidine (1.0 g, 7.7 mmol, Asta Tech, Inc.) in THF was slowly added. After complete addition, the reaction mixture was stirred at rt for 12 h, diluted with water, and extracted with EtOAc. The organic phase was concentrated in vacuo to give 474 (methoxy-d3)pyrimidine-2-amine (0.81 g, 6.3 mmol, 82% yield). The crude product was used in the next step without further purification. LC / MS (ESI+) m / z = 129.2 [M+H]+. STEP 2: 8-(METHOXY-D3)-2-(TRIFLUOROMETHYL)-4H-PYRIMIDORi.2-A1PYRIMIDIN-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-(methoxy3)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 (ESI+) m / z = 249.1 [M+H]+. Ή NMR (400 MHz, CDCl3) δ 9.06 (d, J=7.67 Hz, 1H), 6.76 (d, J=7.67 Hz, 1H), 6.71 (s, 1H). STEP 3: 3-BROMO-8-(METHOXI-D3)-2-(TRIFLUOROMETHYLMH-PYRIMIDOri,2-A1PYRIMIDIN4-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[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 327.0 / 329.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 9.06 (d, J=7.67 Hz, 1H), 7.12 (d, J=7.67 Hz, 1H). INTERMEDIATE 1-S 3-BROMINE-2-(FLUOROMETHYL)-8-METHOXY-4H-PYRIDON,2-A1PYRIMIDIN-4-ONE Step 1 Step 2 STEP 1: 2-(FLUOROMETHYL)-8-METHOXY-4H-PYRIDON,2-A1PYRIMIDIN-4-ONES. 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, methanesulfonic acid (0.5 mL, 8 mmol) was added. Heating was continued for 1 h. The reaction mixture was cooled to rt and treated with CH2Cl2 (20 mL) and water (40 mL). The pH was adjusted to pH = 14 by the dropwise addition of 5M NaOH solution. The organic phase was separated, washed with brine (5 mL), dried over MgSO4, then concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 0-40% (EtOAc / EtOH 3:1) / heptane) to afford 2-(fluoromethyl)-8-methoxy-4H-pyrido[1,2-a]pyrimidin-4-one (40 mg, 0.19 mmol, 5% yield) as a white solid. LC / MS (ESI+) m / z = 209.1 [M+H]+.1H NMR (400 MHz, CDCl3) δ 8.93 (d, J=7.46 Hz, 1H), 6.77-6.83 (m, 2H), 6.40-6.45 (m, 1H), 5.28 (t, J=46.60 Hz, 3H), 3.96 (s, 3H). STEP 2: 3-BROMO-2-(FLUOROMETHYL)-8-METHOXY-4H-PYRIDORi.2-A1PYRIMIDIN4-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)75 8-methoxy-4H-pyrido[1,2-a]primidin-4-one. LC / MS (ESI+) m / z = 287.0 / 289.0 [M+H]+.1H NMR (400 MHz, CDCI3) δ 8.95 (d, J=7.88 Hz, 1H), 7.07 (d, J=2.49 Hz, 1H), 6.91 (dd, J=2.49, 7.88 Hz, 1H), 5.53 (d, J=46.65 Hz, 2H), 3.98-4.01 (m, 3H). INTERMEDIATE 1-T 3-BROMINE-2-ETHYL-8-METHOXY-4H-PYRIDori,2-A1PYRIMIDIN-4-ONE STEP 1: 2-ETHYL-8-METHOXY-4H-PYRIDori,2-A1PYRIMIDIN-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 (ESI+) m / z = 205.1 [M+H]+.1H NMR (400 MHz, CDCh) δ 8.90 (dd, J=8.0, 1.1 Hz, 1H), 6.90 - 6.85 (m, 1H), 6.77 (ddd, J=7.9, 2.7, 1.1 Hz, 1H), 6.19 (d, J=1.1 Hz, 1H), 3.96 (d, J=1.2 Hz, 3H), 2.67 (qd, J=7.6, 1.1 Hz, 2H), 1.31 (td, J=7.6,1.2 Hz, 3H). STEP 2: 3-BROMO-2-ETHYL-8-METHOXY-4H-PYRIDO[1,2-A1PYRIMIDIN-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-methoxyH-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 283.0 [M+H]+.1H NMR (400 MHz, CDCl3) 8.89 (t, J=7.7 Hz, 1H), 6.86 (dd, J=7.2, 2.8 Hz, 1H), 6.80 (cd, J=7.8, 2.7 Hz, 1H), 3.97 (d, J=4.0 Hz, 3H), 2.91 (p, J=7.4 Hz, 2H), 1.31 (td, J=7.4, 5.2 Hz, 3H). INTERMEDIATE 1-U 3-BROMINE-2-CYCLOPROPYL-8-METHOXY-4H-PYRIDori,2-A1PYRIMIDIN-4-ONE STEP 1: 2-CYCLOPROPYL-8-METHOXI-4H-PYRIDori,2-A1PYRIMIDIN-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-3-oxopropanoate (Accela ChemBio Inc.). LC / MS (ESI+) m / z = 217.2 [M+H]+. STEP 2: 3-BROMO-2-CYCLOPROPYL-8-METHOXY-4H-PYRIDON.2-A1PYRIMIDIN-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[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 295.0 / 297.0 [M+H]+. INTERMEDIATE 1-V 3-BROMO-8-(DIFLUOROMETHOXI)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4ONE Intermediate Step 1 Step? STEP 1: 8-(DIFLUOROMETHOXY)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4ONE· Difluoromethyl trifluoromethanesulfonate (0.4 g, 2.2 mmol, prepared according to the procedure described in Levin et al., Journal of Fine Chemical Chemistry 130 (2009) 667–670) was added to a suspension of 8-hydroxy-2-(trifluoromethyl)-4H-pyrido[1,2-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). The reaction mixture was stirred for 10 min at rt. 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 N NaOH. The organic layer was washed with additional 1 N 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[1,2-a]pyrimidine-4-one (0.1 g, 0.36 mmol) (combined yield). MS (ESI+) m / z = 281.0 [M+H]+. STEP 2: 3-BROMO-8-(DIFLUOROMETHOXI)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2A1PYRIMIDIN-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[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 358.8 [M+H]+.1H NMR (400 MHz, CD2Cl2) δ 6.98-7.38 (m, 1H) 7.38-7.42 (m, 1H) 7.80 (d, J=7.67 Hz, 1H) 8.99 (dd, J=7.26, 1.04 Hz, 1H). INTERMEDIATE 1-W 3-BROMO-8-METHOXY-2-METHYL-4H-PYRIDOI1,2-A1PYRIMIDIN-4-ONE STEP 1: 8-METHOXY-2-METHYL-4H-PYRIDori,2-A1PYRIMIDIN-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 (ESI+) m / z = 191.2 [M+H]+. STEP 2: 3-BROMO-8-METHOXY-2-METHYL-4H-PYRIDOri.2-A1PYRIMIDIN-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-pyrido[1,2-a]pyrimidin-4-one. 1H NMR (400 MHz, CDCl3) δ 8.91 (d, J=7.88 Hz, 1H), 6.86 (d, J=2.49 Hz, 1H), 6.82 (dd, J=7.88, 2.70 Hz, 1H), 3.97 (s, 3H), 2.62 (s, 3H). INTERMEDIATE 1-X 3-BROMO-8-CYCLOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE. STEP 1: 8-CYCLOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-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 (ESI+) m / z = 255.1 [M+H]+. STEP 2: 3-BROMO-8-CYCLOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDOM.2-A1PYRIMIDIN4-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[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 332.9 [M+H]+.1H NMR (CDCl3, 400 MHz) δ 8.98 (d, J=7.5 Hz, 1H), 7.44 (d, J=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). INTERMEDIATE 1-Y 8-FLUORO-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONE Step 2 STEP 1: 8-FLUORO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONE· Potassium fluoride (0.3 g, 5.2 mmol) was added to a solution of 8-bromo-2(trifluoromethyl)-4H-p¡hdo[1,2-a]pyrimid¡n-4-one (0.5 g, 1.7 mmol, Intermediate 3-C) in DMSO (5 mL) under a nitrogen atmosphere. 18-Crown-6 (23 mg, 0.085 mmol) was added and the resulting reaction mixture was heated at 100 °C for 6 h. The reaction mixture was cooled to rt and quenched by the addition of ice (10 g). Stirring was continued for 15 min and the resulting precipitate was filtered off. The solid was washed with water (3x5 mL) and dried under reduced pressure to afford 8-fluoro-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (0.3 g, 76% yield). LC / MS (ESI+) m / z = 233.1 [M+H]+.1H NMR (400 MHz, CDCl3) δ 9.15 (dd, J=8.0, 6.2 Hz, 1H), 7.44 (dd, J=8.5, 2.8 Hz, 1H), 7.14 (ddd, J=8.6, 6.2, 2.8 Hz, 1H), 6.77 (s, 1H). STEP 2: 8-FLUORO-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-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-fluoro-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESC) m / z = 359.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 9.13-9.08 (m, 1H), 7.86 (dd, J=9.2, 2.8 Hz, 1H), 7.63-7.57 (m, 1H). Intermediate 1-Z 3-IODOINE-8-(METHYL-D3)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE Intermediate 3-C Step 1 Step 2 STEP 1: 8-(METHYL-D3)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE· Cobalt(II) chloride (0.2 g, 1.5 mmol) was added to a solution of 8-bromo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (1.0 g, 3.4 mmol, Intermediate 3-C) in benzene (15 mL) at rt under a nitrogen atmosphere. A separately prepared solution consisting of magnesium turnings (0.33 g, 13.7 mmol) and trideuteromethyl 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 2 h. The reaction mixture was cooled to room temperature and quenched by the 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 the addition of NaHCO3, 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-(rnetyl-d3)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidín-4-one (0.32 g, 40%) as a yellow solid. LC / MS (ESP) m / z = 232.2 [M+H]+.1H NMR (400 MHz, CDCI3) δ 9.01 (d, J=7.3 Hz, 1H), 7.62 (d, J=1.8 Hz, 1H), 7.14 (dd, J=7.3, 1.9 Hz, 1H), 6.74 (s, 1H). STEP 2: 3-IODOINE-8-(METHYL-D3)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4ONA· 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-(methyl-d3)-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESP) m / z = 358.0 [M+H]+.1H NMR (400 MHz, CDCl3) δ 9.03 (d, J=7.3 Hz, 1H), 7.64 (d, J=1.9 Hz, 1H), 7.19 (dd, J=7.3, 1.8 Hz, 1H). INTERMEDIATE 2-A 2-(4-((2,2-DIFLUOROCYCLOPROPYL)METHOXY)PHENYL)-4,4,5,5-TETRAMETHYL-1,3,2DIOXABOROLANE F Pd(dppf)CI; KOAc, DMF Paso ? PASO 1: 1-((2,2-DIFLUOROCICLOPROPIL)METOXI)-4-YODOBENCENO. DIAD (3.6 g, 18 mmol) was added dropwise to a stirred solution of 4-iodophenol (3.4 g, 15 mmol) and triphenylphosphine (4.7 g, 18 mmol) in tetrahydrofuran (34 mL) under a nitrogen atmosphere at 0 °C. After 10 min, (2,2-difluorocyclopropyl)methanol (1.5 g, 14 mmol) was added dropwise, and the reaction mixture was allowed to warm to rt and further stirred for 16 h. The reaction was quenched by the addition of ice-water (100 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were dried over Na2SO4, 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% ethyl acetate / hexane) to afford 1-((2,2-difluorocyclopropyl)methoxy)-4-iodobenzene (1.8 g, 5.8 mmol, 42% yield). LC / MS (ESP) m / z = 311.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 7.62-7.56 (m, 2H), 6.84-6.78 (m, 2H), 4.12 (ddd, J=10.3, 6.6, 3.1 Hz, 1H), 3.95 (ddd, J=10.6, 8.5, 1.8 Hz, 1H), 2.26–2.14 (m, 1H), 1.71 (tdd, J=12.1,7.9, 4.8 Hz, 1H), 1.50–1.41 (m, 1H). STEP 2: 2-(4-((2,2-DIFLUOROCYCLOPROPYL)METHOXY)PHENYL)-4,4.5,5-TETRAMETHYL-1,3.2DIOXABOROLANE· Into a resealable vial were placed 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)Cl2 (0.38 g, 0.52 mmol) was added. The reaction mixture was heated to 90 °C for 16 h. The reaction mixture was filtered through a pad of celite, and the filtrate was concentrated under reduced pressure. The crude material was purified by silica gel chromatography (eluent: 0-5% ethyl acetate / hexane) to provide 2-(4-((2,2-difluoroc!clopropyl)methoxy)phenyl)-4,4,5,5tetramethyl-1,3,2-dioxaborolane (950 mg, 60% yield). 1H NMR (400 MHz, DMSO-de) δ 7.64-7.59 (m, 2H), 6.97 (dd, J=8.7, 2.6 Hz, 2H), 4.17 (d, J=8.1 Hz, 1H), 4.00 (t, J=9.2 Hz, 1H), 2.25(s, 1H), 1.74 (d, J=9.1 Hz, 1H), 1.52-1.44 (m, 1H), 1.30-1.27 (m, 12H). INTERMEDIATE 2-B 2-PHENYL-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)OXAZOLE STEP 1: 5-BROMO-2-PHENYLOXAZOLE· 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 2 h. The reaction mixture was cooled 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% ethyl acetate / hexane) to afford 5-bromo-2-phenyloxazole (4.2 g, 46% yield). LC / MS (ESI+) m / z = 224.0 [M+H]+. Ή NMR (400 MHz, CDCI3) δ 8.05 - 7.99 (m, 2H), 7.52 - 7.46 (m, 3H), 7.13 (d, J=1.4 Hz, 1H). STEP 2: 2-PHENYL-5-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)OXAZOLE· N-Butyllithium (1.6 M in hexane, 0.61 mL, 0.982 mmol) was added to a solution of 5-bromo-2-phenyloxazole (200 mg, 0.89 mmol) in tetrahydrofuran (6 mL) at -78 °C under a nitrogen atmosphere. The reaction mixture was stirred at -78 °C for 10 min, after which triisopropyl borate (201 mg, 1.1 mmol) was added. 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 µL, 1.1 mmol) were added, and stirring was continued at rt for 1 h. The reaction mixture was concentrated under reduced pressure to obtain a crude residue (400 mg), which was used without further purification. INTERMEDIATE 2-C 2-(4-(2,2-DIFLUOROETHOXY)PHENYL)-4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLANE FF STEP 1: 2-(4-(2,2-DIFLUOROETHOXY)PHENYL)-4,4,5,5-TETRAMETHYL-1,3,2DIOXABOROLANO· A mixture of 4-hydroxyphenylboronic acid pinacolic ester (1.0 g, 4.5 mmol), dimethyl sulfoxide (20 mL), cesium carbonate (2.2 g, 6.8 mmol), and 1,1-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 over Na2SO4, and concentrated in vacuo. The crude residue was purified by silica gel chromatography (eluent: 0-50% EtOAc / heptane) to obtain 2-(4-(2,2-difluoroethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2dioxaborolane (1.18 g, 4.15 mmol, 91% yield). LC / MS (ESI+) m / z = 285 [M+H]+.1H NMR (400 MHz, CDCI3) δ 1.33 (s, 12H)4.11 -4.31 (m, 2H) 5.86-6.27 (m, 1H) 6.91 (d, J=8.71 Hz, 2H) 7.77 (d, J=8.71 Hz, 2H). INTERMEDIATE 2-D 4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1 -(3,3,3- STEP 1: 4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1-(3,3,3TRIFLUOROPROPIDPYRAZOLE, 4-Pyrazoleboronic acid pinacolic ester (500 mg, 2.6 mmol), acetonitrile (5 mL), cesium carbonate (1.7 g, 5.1 mmol), and 1,1,1-trifluoro-3-iodopropane (604 μI, 5.15 mmol, Oakwood) were placed in a resealable vial. The reaction mixture was heated to 80 °C for 12 h. The reaction mixture was cooled to rt and filtered through a pad of celite with EtOAc. The filtrate was washed with brine, and the organic layer 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)-1-(3,3,3-trifluoropropyl)-1H-pyrazole (137 mg, 0.47 mmol, 18% yield). Ή NMR (400 MHz, CDCl3) δ 1.32 (s, 13H) 2.74 (dt, J=10.37, 7.36 Hz, 2H) 4.37 (t, J=7.36 Hz, 2H) 7.71 (s, 1H) 7.81 (s, 1H). INTERMEDIATE 2-E 4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1 -(4,4,4TRIFLUOROBUTYL)PYRAZOLE STEP 1: 4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1-(4,4,4TRIFLUOROBUTIL)PYRAZOLE· 4-Pyrazoleboronic acid pinacolic ester (500 mg, 2.58 mmol), acetonitrile (5 mL), potassium carbonate (0.53 g, 3.8 mmol), and 1,1,1-trifluoro-4-iodobutane (0.7 mL, 5.2 mmol, Oakwood) were placed in a resealable vial. 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)-1-(4,4,4-trifluorobutyl)-1H-pyrazole (508 mg, 1.7 mmol, 65% yield).1H NMR (400 MHz, CDCl3) δ 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-TETRAMETHYL-1,3,2DIOXABOROLANO PASO 1: 1-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). The reaction mixture was heated to 100 °C for 12 h. Additional 2,2,2-trifluoroethyl iodide (1.5 mL) was added and stirring was continued for 12 h. The reaction mixture was cooled to rt and filtered with ethyl acetate through a pad of celite. The filtrate was washed with water and brine, and dried over Na2SO4. The filtrate was concentrated under reduced pressure and the crude residue was purified by silica gel 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). 1H NMR (CDCl3, 400MHz): δ = 7.48 (dd, J=8.8, 7.8 Hz, 1H), 6.77 (dd, J=9.8, 2.7 Hz, 1H), 6.67 (ddd, J=8.9, 2.9, 1.2 Hz, 1H), 4.34 (q, J=8.0 Hz, 2H). STEP 2: 2-(2-FLUORO-4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-4,4,5.5-TETRAMETHYL-1,3,2DIOXABOROLANO· 1-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) were placed in a resealable vial. The reaction mixture was purged with argon for 5 min, followed by the addition of Pd(dppf)Cl2 (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 through a pad of celite with ethyl acetate. 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)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.37 g, 4.3 mmol, 76% yield).1H NMR (CDC / 3, 400MHz): δ = 7.69 (dd, J=8.3, 7.1 Hz, 1H), 6.72 (dd, J=8.4, 2.3 Hz, 1H), 6.61 (dd, J=10.6, 2.3 Hz, 1H), 4.35 (q, J=8.0 Hz, 2H), 1.34 (s, 12H). INTERMEDIATE 2-G 1-(2,2,3,3,3-PENTAFLUOROPROPIL)-4-(4,4,5,5-TETRAMETIL-1,3,2-DIOXABOROLAN-2IL)-1H-PIRAZOL K2CO3, DMF Paso 1 PASO 1: 1 -(2,2,3,3,3-PENTAFLUOROPROPIL)-4-(4,4,5,5-TETRAMETIL-1,3,2DIOXABOROLAN-2-IL)-1 H-PIRAZOL. 4-Pyrazoleboronic acid pinacolic 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) were charged into a resealable vial. The reaction mixture was heated to 80 °C for 12 h. 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)-1l-lpyrazole (289 mg, 0.9 mmol, 34% yield) which was used in the next reaction without further purification.1H NMR (400 MHz, CDCh) δ 1.32 (s, 16H) 4.75 (t, J=14.10 Hz, 2H) 7.80 (s, 1H) 7.84 (s, 1H). INTERMEDIATE 2-H 3-(4-(4,4,5.5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1 H-PYRAZOLE-1 IL)PROPANONITRILE STEP 1: 3-(4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1H-PYRAZOLE-1IL)PROPANONITRILE. 3-Bromopropionitrile (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-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-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. The 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 Na2SO4. The filtrate was concentrated under reduced pressure to give 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanoniritrile (2.5 g, 10.1 mmol, 98% yield) as a yellow liquid which was used for the next step without further purification. LC / MS (ESI+) m / z = 248.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.04 (s, 1H), 7.65 (s, 1H), 4.41 (t, J=6.4 Hz, 2H), 3.07 (t, J=6.4 Hz, 2H), 1.26 (s, 12H). INTERMEDIATE 2-I 2-(4-(4,4.5.5-TETRAMETHYL-1,3.2-DIOXABOROLAN-2-IL)-1 H-PYRAZOLE-1 -IL)ACETONITRIL STEP 1: 2-(4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1H-PYRAZOLE-1IDACETONITRIL· The 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-1,3,2-dioxaborolan-2-yl)-1H-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]+.1H NMR (400 MHz, CDCl3) δ 7.85 (s, 2H), 5.10 (s, 2H), 1.33 (s, 12H). INTERMEDIATE 2-J 1-(2,2-DIFLUOROPROPIL)-4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1HPYRAZOLE STEP 1: 4-BROMO-1-(2,2-DIFLUOROPROPYL)-1H-PYRAZOLE· A solution of diethylaminosulfur trifluoride (0.84 mL, 6.3 mmol) in DCM (2 mL) was added dropwise to a solution of 1-(4-bromo-1H-pyrazol-1-yl)propan-2-one (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. The 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-1-(2,2-difluoropropyl)-1H-pyrazole (220 mg, 0.98 mmol, 61% yield). 1H NMR (400 MHz, CDCl3) δ 1.57 (t, J=18.66 Hz, 3H) 4.43 (t, J=12.02 Hz, 2H) 7.51 (s, 1H) 7.53 (s, 1H). STEP 2: 1-(2,2-DIFLUOROPROPYL)-4-(4,4,5.5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)1H-PYRAZOLE. 4-Bromo-1-(2,2-difluoropropyl)-1H-pyrazole (0.31 g, 1.4 mmol), bis(acetonitrile)dichloropalladium(II) (11 mg, 0.04 mmol, Strem), and 2-dicyclohexylphosphino2,6'-dimethoxy-1,2-phenyl (51 mg, 0.12 mmol, Strem) were placed in a resealable vial. The vial was evacuated and filled 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). More toluene (0.7 ml) was added. The reaction mixture was heated to 90°C for 12 h. The reaction mixture was filtered through a plug of silica gel and concentrated under reduced pressure. 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-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole (164 mg, 0.6 mmol, 44% yield). 1H NMR (400 MHz, CDCh) δ 1.33 (s, 12H) 1.56 (m, 3H) 4.47 (t, J=12.02 Ηζ, 2H) 7.79 (s, 1H) 7.81 (s, 1H). INTERMEDIATE 2-K 2-(FLUOROMETHYL)-3-YODO-4-OXO-4H-PYRIDOf1,2-A1PYRIMIDINE-8-CARBONITRILO STEP 1: 2-(FLUOROMETHYL)-4-OXO-4H-PYRIDO-2-A1PYRIMIDINE-8-CARBONITRILO. Polyphosphoric acid (~700 µL) was added to a suspension of ethyl 4-fluoro-3-oxobutanoate (0.4 g, 2.7 mmol, HCH Pharma) and 2-aminopyridine-4-carbonitrile (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. The 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[1,2-a]pyrimidine-8-carbonitrile (290 mg, 1.43 mmol, 53% yield). LC / MS (ESI+) m / z = 204.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 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-(FLUOROMETHYL)-3-IODO-4-OXO-4H-PYRIDO[1.2-A1PYRIMIDIN-8CARBONITRILE. The title compound was prepared using the procedure described for Intermediate 1-B, Step 2 with the following modification: Step 2 was performed with 2-(fluoromethyl)4-oxo-4H-pyrido[1,2-a]pyrimidine-8-carbonyltrimethylammonium chloride. LC / MS (ESI+) m / z = 402.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 5.43 - 5.64 (d, 2H) 7.64 (d, J=7.48,1H) 8.49 - 8.54 (s, 1H) 8.96 - 9.03 (d, 1H). INTERMEDIATE 2-L (2-FLUORO-4-(2,2,2-TRIFLUOROETHOXY)PHENYL)BORONIC ACID Intermediate 2 F STEP 1: (2-FLUORO-4-(2,2,2-TRIFLUOROETHOXY)PHENYL)BORONIC ACID 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-1,3,2-dioxaborolane (0.25 g, 0.78 mmol, Intermediate 2-F) in THF:water and concentrated under reduced pressure to afford (2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)boronic acid. 1H NMR (400 MHz, DMSO-ds) δ 8.02 (s, 1H) 7.49-7.81 (m, 1H) 6.76-6.97 (m, 2H) 4.81 (c, J=8.85 Hz, 2H). (1:1, 10 ml) and 1N 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-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1 -(2,2,2-TRIFLUOROETIL)-1 HPYRAZOLE STEP 1: 4-(4,4,5.5-TETRAMETHYL-1.3.2-DIOXABOROLAN-2-ILM -(2,2.2-TRIFLUOROETIL) 1H-PYRAZOLE. 2,2,2-Trifluoroethyl triflate (0.37 mL, 2.6 mmol, Oakwood Products) was added to a mixture of 4-pyrazoleboronic acid pinacolic 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 12 h. 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 concentrated under reduced pressure. Purification by silica gel chromatography afforded 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(2,2,2-trifluoroethyl)-1 H-pyrazole (133 mg, 0.48 mmol, 37% yield).1H NMR (400 MHz, CD2CI2) δ 1.30 (s, 13H) 4.74 (q, J=8.41 Hz, 2H) 7.75 (s, 1H) 7.79 (s, 1H). INTERMEDIATE 2-N 2-(3-CHLORINE-4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-4,4,5.5-TETRAMETHYL-1,3,2DIOXABOROLANE STEP 1: 4-BROMO-2-CHLORINE-1-(2,2,2-TRIFLUOROETHOXY)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 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 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). 1H NMR (CDCl3, 400MHz): δ = 7.55 (d, J=2.3 Hz, 1H), 7.36 (dd, J=8.7, 2.4 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 4.38 (c, J=8.0 Hz, 2H). STEP 2: 2-(3-CHLORINE-4-(2,2,2-TRIFLUOROETHOXI)PHENYL)-4,4.5,5-TETRAMETHYL-1,3.2DIOXABOROLANA A mixture of 4-bromo-2-chloro-1-(2,2,2-trifluoroethoxy)benzene (1.7 g, 6.0 mmol), bis(pinacolato)diboron (2.3 g, 9.0 mmol), potassium acetate (2.1 g, 21 mmol), and Pd(dppf)Cb (0.49 g, 0.6 mmol, Strem) in dioxane (20 mL) was purged with argon for 5 min. The reaction mixture was heated to 110 °C for 12 h. The reaction mixture was cooled to 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).1H NMR (CDCl3, 400MHz): δ = 7.77 (d, J=1.6 Hz, 1H), 7.59 (dd, J=8.1, 1.5 Hz, 1H), 6.85 (d, J=8.2 Hz, 1H), 4.35 (q, J=8.0 Hz, 2H), 1.26 (s, 12H). INTERMEDIATE 2-0 3-BROMO-2-FLUORO-6-(2.2,2-TRIFLUOROETHOXY)PYRIDINE K2CO3, DMF Step 1 STEP 1: 3-BROMO-2-FLUORO-6-(2,2,2-TRIFLUOROETHOXY)PYRIDINE· 1,1,1-Trifluoro-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 mg, 2.6 mmol, Combi-Blocks, San Diego, CA, USA) and potassium carbonate (0.72 g, 5.2 mmol) in DMF (5 ml) under argon. 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 Na2SO4, 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 (ESI+) m / z = 274.0 [M+H]+. INTERMEDIATE 2-P 2-BROMINE-5-(2,2,2-TRIFLUOROETHOXY)PYRIDINE l^yx F3C^OH F3C^ON BrKOtBu Step 1 STEP 1: 2-BROMO-5-(2,2,2-TRIFLUOROETHOXY)PYRIDINE. 2,2,2-Trifluoroethanol (0.42 ml, 5.7 mmol), potassium tert-butoxide (1 M in THF, 5.7 ml, 5.7 mmol), 2-bromo-5-fluoropyridine (1.0 g, 5.68 mmol), and THF (6 ml) were placed in a resealable vial. The reaction mixture was heated to 70 °C for 60 hours. The reaction mixture was cooled to room temperature and partitioned between water and EtOAc. The organic phase was dried over MgSO4 and concentrated in vacuo. The crude 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 (ESI+) m / z = 256.0 [M+H]+. INTERMEDIATE 2-Q 5-BROMO-3-FLUORO-2-(2,2,2-TRIFLUOROETHOXY)PYRIDINE Step 1 STEP 1: 5-BROMO-3-FLUORO-2-(2,2,2-TRIFLUOROETHOXY)PYRIDINE. 1,1,1-Trifluoro-2-iodoethane (2.3 ml, 100 mmol, Oakwood Chemical, Estill, SC, USA) was added to a mixture of 5-bromo-3-fluoropindín-2-ol (1.5 g, 7.8 mmol, Combi-Blocks, San Diego, CA, USA) and potassium carbonate (2.2 g, 15.6 mmol) in DMF (10 ml) under argon. 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 Na2SO4, and concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 0-10% ethyl acetate / heptane) to give 5-bromo3-fluoro-2-(2,2,2-trifluoroethoxy)pyridine (1.28 g, 4.67 mmol, 60% yield). LC / MS (ESI+) m / z = 274.0 [M+H]+. INTERMEDIATE 2-R 5-BROMINE-2-(2,2,2-TRIFLUOROETHOXY)PYRIDINE F3C OH FjC^OBrKOtBu Step 1 STEP 1: 5-BROMO-2-(2,2,2-TRIFLUOROETHOXY)PYRIDINE. The title compound was prepared using the procedure described for Intermediate 2-P, Step 1 with the following modification: Step 1 was performed with 5-bromo-2-fluoropyridine. LC / MS (ESI+) m / z = 255.8 [M+H]+ / 258.0 [M+2]+. Intermediate 2-S (2-METHYL-4-(2,2,2-TRIFLUOROETHOXY)PHENYL)BORONIC ACID STEP 1: 1-BROMO-2-METHYL-4-(2,2,2-TRIFLUOROETHOXY)BENZENE. 4-Bromo-3-methylphenol (1 g, 5.4 mmol), 1,1,1-trifluoro-2-iodoethane (4.5 g, 21.4 mmol, Oakwood), DMF (5 ml), and cesium carbonate (3.5 g, 10.7 mmol) were placed in a vial. The reaction mixture was heated to 60 °C for 48 h. 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 MgSO . The filtrate was absorbed onto a pad of silica gel. Purification by silica gel chromatography (eluent: 0-10% (EtOAc / EtOH 3:1) / heptane) gave 1-bromo-2-methyl-4-(2,2,2-trifluoroethoxy)benzene (1.1 g, 4.1 mmol, 76% yield)1H NMR (CDCI3, 400 MHz) δ 7.37 (d, J=8.7 Hz, 1H), 6.77 (d, J=3.1 Hz, 1H), 6.58 (dd, J=8.7, 3.1 Hz, 1H), 4.24 (q, J=8.2 Hz, 2H), 2.31 (s, 3H). STEP 2: 4,4,5,5-TETRAMETHYL-2-(2-METHYL-4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-1,3,2DIOXABOROLANE. The title compound was prepared using the procedure described for Intermediate 2-N, Step 2 with the following modification: Step 2 was performed with 1-bromo-2-methyl-4-(2,2,2-trifluoroethoxy)benzene. 1H NMR (CDCI3, 400 MHz) δ 7.74 (da, J=8.3 Hz, 1H), 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-METHYL-4-(2,2,2-TRIFLUOROETHOXY)PHENYL)BORONIC ACID. 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)-1,3,2-dioxaborolane. 1H NMR (DMSO-d, 400 MHz) δ 7.83 (d, J=9.1 Hz, 1H), 6.76-6.93 (m, 2H), 4.73 (q, J=8.9 Hz, 2H), 2.61-2.65 (m, 3H). INTERMEDIATE 2-T 8-CHLORINE-3-IODOINE-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONE Intermediate 3-C HCI CH3CN Step 1 Step 2 STEP 1: 8-CHLORINE-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONE· Concentrated hydrochloric acid (37%, 3.4 mL, 41 mmol) was added to a solution of 8-bromo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyridine-4-one (2.0 g, 6.8 mmol, Intermediate 3-C) in acetonitrile (16 mL). The resulting mixture was then subjected to microwave irradiation at 100 °C for 15 min. The mixture was slowly quenched with saturated NaHCO3 (200 mL) and extracted with EtOAc (2 x 200 mL). The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure. Purification of the crude residue by silica gel chromatography (eluent: 0%-100% EtOAc / heptane) gave 8-chloro-2-(trifluoromethyl)4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 249.1 [M+H]+.1H NMR (DMSO-d6) δ: 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-CHLORINE-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-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-chloro-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 374.9 [M+H]+.1H NMR (DMSO-d6) δ 8.96 (d, J=7.7 Hz, 1H), 8.10 (d, J=2.1 Hz, 1H), 7.59 (dd, J=7.7, 2.3 Hz, 1H). INTERMEDIATE 2-U 3-IODOINE-2-(TRIFLUOROMETHYL)-8-VINYL-4H-PYRIDE M.2-A1 PYRIMIDIN-4-ONE OO H . Tributyl(vinyl)tin Pd(PPh3)4,toluene Step 1 Intermediate 3-I Tributyl(vinyl)tin (0.90 g, 2.86 mmol) was added to a solution of 8-bromo-3-iodo-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (1.0 g, 2.38 mmol, Intermediate 3-I) in toluene (10 mL). The reaction mixture was purged with nitrogen for 10 min and Pd(PPh3)4 (276 mg, 0.24 mmol) was added. The reaction mixture was heated to 110 °C for 12 h. 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 give 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]+.1H NMR (400 MHz, DMSO-d6) δ 8.93 (d, J=7.5 Hz, 1H), 7.91 (d, J=1.8 Hz, 1H), 7.79 (dd, J=7.6, 1.9 Hz, 1H), 6.96 (dd, J=17.6, 10.9 Hz, 1H), 6.42 (d, J=17.7 Hz, 1H), 5.82 (d,J=10.9Hz, 1H). INTERMEDIATE 2-V 3-BROMO-8-METHYL-2-(TRIFLUOROMETHYL)-4H-PYRIDON.2-A1PYRIMIDIN-4-ONE Step 1 Step 2 STEP 1: 8-METHYL-2-(TRIFLUOROMETHYL)-4H-PYRIDIN,2-A1PYRIMIDIN-4-ONE. The title compound was prepared using the procedure described for Intermediate 1-O, Step 1-1 with the following modification: Step 1-1 was performed with 2-amino-4-methylpyridine. LC / MS (ESI+) m / z = 229.9 [M+H]+.1H NMR (400 MHz, CDCl3) δ 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-METHYL-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1.2-A1PYRIMIDIN-4-ONE. The title compound was prepared using the procedure described for Intermediate 1-O, Step 1-2 with the following modification: Step 1-2 was performed with 8-methyl-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 307.0 [M+H]+. INTERMEDIATE 2-W 3-IODO-2,8-DIMETHOXY-4H-PYRIDO[1,2-AfPYRIMIDIN-4-ONE OO Step 3 Step 4 Step 1: Ethyl 3-((4-Methoxypyridin-2-yl)amino)-3-oxopropanoate. A solution of ethylmalonyl 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. Saturated aqueous sodium carbonate was added and the organic layer was separated. The aqueous phase was extracted with DCM, the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The raw material was purified by silica gel chromatography (eluent: 0-25% of (EtOAc / EtOH 3:1) / heptane) to provide ethyl 3-((4-metox¡p¡r¡din-2-¡l)amino)-3-oxopropanoate of ethyl (1.54 g, 6.5 mmol, 32% of yield).1H RMN (400 MHz, CDCh) δ 9.45 (sa, 1H), 8.09 (d, J=5.80 Hz, 1H), 7.80 (s, 1H), 6.60 (dd, J=2.28, 5.80 Hz, 1H), 4.25 (c, J=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-METHOXI-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONA. A mixture of ethyl 3-((4-methoxypyridin-2-yl)amino)-3-oxopropanoate (1.0 g, 4.3 mmol), phosphorus 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, after which EtOH (4.3 mL) was added. The reaction mixture was further heated under reflux for 30 min, then allowed to cool to rt. The reaction mixture was partitioned between EtOAc and brine. The aqueous layer was back-extracted with EtOAc (x2), and the combined organic layers were dried over Na2SO4. 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[1,2-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-DIMETHOXI-4H-PYRIDOÍ1,2-A1PYRIMIDIN-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[1,2-a]pyrimidin-4-one (213 mg, 1.0 mmol) in acetonitrile (2 mL). The reaction mixture was stirred at rt for 2 h, after which it was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layers were dried over Na2SO4. The filtrate was concentrated to give 2,8-dimethoxy-4H-pyrido[1,2-a]pyrimidin-4-one (172 mg, 0.83 mmol, 82% yield) as an off-white solid. LC / MS (ESI+) m / z = 207.2 [M+H]+. STEP 4: 3-IODO-2,8-DIMETHOXI-4H-PYRIDOri,2-A1PYRIMIDIN-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 2,8-dimethoxy-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 333.0 [M+H]+. INTERMEDIATE 2-X 2-ETHOXY-3-IODO-8-METHOXY-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE Step 1 Step 2 STEP 1: 2-ETHOXY-8-METHOXY-4H-PYRIDON.2-A1PYRIMIDIN-4-ONE· Sodium ethoxide (254 mg, 0.78 mmol) was added to a solution of 2-chloro-8-methoxy-4H-pyrido[1,2-a]pyrimidin-4-one (150 mg, 0.71 mmol, prepared according to the 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, after which it was partitioned 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% (EtOAc / EtOH 3:1) / heptane) to afford 2-ethoxy-8-methoxy-4H-pyrido[1,2-a]pyrimidin-4-one (85 mg, 0.39 mmol, 54% yield) as a white solid. LC / MS (ESP) m / z = 221.1 [M+H]+. STEP 2: 2-ETHOXY-3-IODO-8-METHOXY-4H-PYRIDON.2-A1PYRIMIDIN-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 2-ethoxy-8-methoxy-4H-pyrido[1,2-a]pyridine-4-one. LC / MS (ESI+) m / z = 347.0 [M+H]+. INTERMEDIATE 2-Y 3-(4-HYDROXY-2-(TRIFLUOROMETHYL)PHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4HPYRIDOÍI .2-A1PYRIMIDIN-4-ONE Intermediate 1 to Step 1 STEP 1: 3-(4-HYDROXY-2-(TRIFLUOROMETHYL)PHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)4H-PYRIDO[1,2-A1PYRIMIDIN-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[1,2-a]pyrimidine-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 (ESP) m / z = 404.9 [M+H]+.1H NMR (DMSO-d6, 400 MHz) δ 10.18-10.39 (m, 1H), 8.88 (d, J=7.9 Hz, 1H), 7.31 (d, J=2.7 Hz, 1H), 7.14-7.23 (m, 3H), 7.09 (d, J=8.6 Hz, 1H), 4.05 (s, 3H). INTERMEDIATE 2-Z 3-(2-CHLORO-4-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDON.2A1PYRIMIDIN-4-ONE Intermediate 1 Λ Step 1 STEP 1: 3-(2-CHLORO-4-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2A1PYRIMIDIN-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[1,2-a]pyrimidin-4-one (1 g, 3.1 mmol, Intermediate 1-A) and 2-chloro-4-hydroxyphenylboronic acid (800 mg, 4.6 mmol, Combi-Blocks Inc.). LC / MS (ESP) m / z = 371.0 [M+H]+. Ή NMR (DMSO-d6, 400 MHz) δ 10.03 (sa, 1H), 8.89 (d, J=7.9 Hz, 1H), 7.31 (d, J=2.7 Hz, 1H), 7.21 (dd, J=7.9, 2.9 Hz, 1H), 7.12 (d, J=8.3 Hz, 1H), 6.93 (d, J=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-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE Step 1 Intermediate 1-A STEP 1: 3-(4-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2A1PYRIMIDIN-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[1,2-a]pyrimidine-4-one (1 g, 3.1 mmol, Intermediate 1-A) and (4-hydroxyphenyl)boronic acid (0.63 g, 4.6 mmol, Combi-Blocks Inc.). LC / MS (ESP) m / z = 337.0 [M+H]+.1H NMR (400 MHz, CDCI3) δ 8.97 (d, J=7.88 Hz, 1H), 7.14 (d, J=8.29 Hz, 2H), 7.07 (d, J=2.49 Hz, 1H), 6.94 (dd, J=2.70, 7.88 Hz, 1H), 6.79 (d, J=8.50 Hz, 2H), 6.47 (sa, 1H), 4.00 (s, 3H). INTERMEDIATE 3-B 3-(4-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIMIDOri,2-A1PYRIMIDIN-4- ONA Step 1 STEP 1: 3-(4-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIMIDOri,2A1PYRIMIDIN-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 3-bromo-8-methoxy-2-(trifluoromethyl)pyrimido[1,2-a]pyrimdin-4-one (2.0 g, 6.2 mmol, Intermediate 1-0), (4-hydroxyphenyl)boronic acid (1.0 g, 7.4 mmol, Combi-Blocks Inc.). LC / MS (ESI+) m / z = 338.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 9.60 (s, 1H), 9.01 (d, J=7.7 Hz, 1H), 7.18-7.00 (m, 3H), 6.836.78 (m, 2H), 4.10 (s, 3H). INTERMEDIATE 3-C 8-BROMINE-2-(TRIFLUOROMETHYL)-4H-PYRIDOf1,2-A1PYRIMIDIN-4-ONE Step 1 STEP 1: 8-BROMO-2-(TRIFLUOROMETHYL)-4H-PIRIDOri.2-A1PYRIMIDIN-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 4-bromopyridin-2-amine (Combi-Blocks Inc.). LC / MS (ESI+) m / z = 294.2 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.88 (d, J=7.6 Hz, 1H), 8.26 (d, J=2.2 Hz, 1H), 7.66 (dd, J=7.6, 2.1 Hz, 1H), 6.89 (s, 1H). INTERMEDIATE 3-D 8-CYCLOPROPYL-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE Intermediate 3-1 8-Bromo-3-iodo-2-(trifluoromethyl)pyrido[1,2-a]pyrimidine-4-one (150 mg, 0.36 mmol, Intermediate 3-I), Pd(PPh3)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 24 h. 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-cyclopropyl-3-iodo-2-(trifluoromethyl)pyrido[1,2a]pyrimidine-4-one (70 mg, 0.18 mmol, 51% yield) as a yellow solid. LC / MS (ESI+) m / z = 381.1 [M+H]+.1H NMR (400 MHz, CDCI3) δ 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 8-(AZETIDIN-1-IL)-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE In a resealable vial were placed 8-bromo-3-iodo-2-(trifluoromethyl)pyrido[1,2a]pyrimidin-4-one (100 mg, 0.24 mmol, Intermediate 3-I), azetidine hydrochloride (25 mg, 0.26 mmol), copper(I) iodide (11 mg, 0.06 mmol), potassium carbonate (40 mg, 0.29 mmol), and DMF (3 mL). The reaction mixture was heated to 80 °C for 1 h. The reaction mixture was diluted with EtOAc, and washed with saturated aqueous NH4Cl and brine. The organic phase was dried and concentrated in vacuo. The crude residue was purified by silica gel chromatography (eluent: 70% EtOAc / cyclohexane) to give 8-(azetidin-1-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]+.1H NMR (400 MHz, CDCb) δ 2.45 2.71 (m, 2H) 4.06 - 4.42 (bs, 4H) 6.28 - 6.39 (d, 1H) 6.39 - 6.57 (dd, 1H) 8.80 - 8.97 (d, 1H). INTERMEDIATE 3-F 4-OXO-3-(1-(2,2,3.3.3-PENTAFLUOROPROPYL)-1H-PYRAZOLE-4-IL)-2-(TRIFLUOROMETHYL)4H-PYRIDOri.2-A1PYRIMIDIN-8-METHYL CARBOXYLATE Intermediate 1 D Step 1 STEP 1: 4-OXO-3-(1 -(2,2.3.3.3-PENTAFLUOROPROPIL)-1 H-PYRAZOLE-4-IL)-2(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-8-METHYL CARBOXYLATE· 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[1,2-a]pyrimidine-8-carboxylate (0.47 g, 1.2 mmol, Intermediate 1-D), 1-(2,2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H-pyrazole (0.50 g, 1.54 mmol, Intermediate 2-G). LC / MS (ESI+) m / z = 471.1 [M+H]+.1H NMR (400 MHz, CDCI3) δ 9.11 (d, J=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, J=13.9 Hz, 2H), 4.06 (s, 3H). INTERMEDIATE 3-G 8-(ETHYLTHIO)-3-(4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2A1PYRIMIDIN-4-ONE Intermedio 3 with Paso i Paso 2 Pd2(dba)3, SPhos cs2co3,dioxano Step 3 100 STEP 1: 8-(ETHYLTHIO)-2-(TRIFLUOROMETHYL)-4H-PYRIDO-2-A1-PYRIMIDIN-4-ONE Sodium ethanethiolate (3.0 g, 36 mmol) was added to a solution of 8-bromo-2-(t-fluoromethyl)-4H-p-indo[1,2-a]pyrimidin-4-one (3.0 g, 12 mmol, Intermediate 3-C) in water (45 mL) at room temperature. The reaction mixture was heated to 100 °C for 48 h. The reaction mixture was cooled to rt, and partitioned between water (200 mL) and EtOAc (500 mL). The combined organic layers were washed with brine (250 mL) and dried over sodium sulfate. The filtrate concentrated under reduced pressure to obtain crude material was purified by silica gel chromatography (eluent: 0-25% ethyl acetate / hexane) to obtain 8-(ethylthio)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (0.4 g, 1.46 mmol, 12% yield). LC / MS (ESI +) m / z = 275.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.81 (d, J=7.6 Hz, 1H), 7.55 (d, J=2.1 Hz, 1H), 7.36 (dd, J=7.6, 2.1 Hz, 1H), 6.69 (s, 1H), 3.26 (t, J=7.4 Hz, 2H), 1.35 (t, J=7.3 Hz, 3H), 1.29- 1.20 (m, 1H). STEP 2: 8-(ETHYLTHIO)-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-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-(ethylthio)-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI +) m / z = 401.1 [M+H] + .1H NMR (400 MHz, DMSO-d6) δ 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 (ct, J=7.5, 2.4 Hz, 2H), 1.35 (td, J=7.3, 2.0 Hz, 3H). STEP 3: 8-(ETHYLTHIO)-3-(4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-2-(TRIFLUOROMETHYLMHPYRIDOri,2-A1PYRIMIDIN4-ONA· 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[1,2-a]pyrimidin-4-one (0.4 g, 1.0 mmol) and (4-(2,2,2-trifluoroethoxy)phenyl)boronic acid (0.29 g, 1.3 mmol, Combi-Blocks Inc.). LC / MS (ESI +) m / z = 449.0 [M+1]+.1H NMR (400 MHz, DMSO-d6) δ 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, J=8.4 Hz, 2H), 7.15 - 7.09 (m, 2H), 4.82 (c, J=8.9 Hz, 2H), 3.29 - 3.24 (m, 2H), 1.36 (td, J=7.3, 1.2 Hz, 3H). INTERMEDIATE 3-H 4-OXO-3-(4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2A1PYRIMIDIN-8-CARBALDEHYDE 101 STEP 1: 4-OXO-3-(4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-2-(TRIFLUOROMETHYL)-4HPIRIDOri,2-A1PYRIMIDIN-8-CARBALDEHYDE· A solution of DIBAL-H (1M in DCM, 4 mL, 4 mmol) was added dropwise to a solution of methyl 4-oxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)pyrido[1,2-a]pyrimidine-8-carboxylate (1.5 g, 3.36 mmol, Example 1-36) in dichloromethane (30 mL) at -40 °C. Stirring was continued for 5 min, after which 1N aq. HCl (20 mL) was added. The reaction mixture was extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-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 [M+1] +. INTERMEDIATE 3-1 8-BROMINE-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDON,2-A1PYRIMIDIN-4-ONE Intermediate 3-C STEP 1: 8-BROMO-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-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-bromo-2(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESI+) m / z = 419.0 [M+H]+. INTERMEDIATE 3-J 8-HYDROXY-2-(TRIFLUOROMETHYL)-3-(1-(3,3,3-TRIFLUOROPROPYL)-1H-PYRAZOLE-4-IL)-4HPYRIDOn .2-A1PYRIMIDIN-4-ONE Example 1-69 STEP 1: 8-HYDROXY-2-(TRIFLUOROMETHYL)-3-(1-(3,3,3-TRIFLUOROPROPYL)-1H-PYRAZOLE 4-IL)-4H-PYRIDOf1.2-A1PYRIMIDIN-4-ONE. The 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-(trifluoromethyl)-3[1-(3,3,3-trifluoropropyl)pyrazol-4-yl]pyrido[1,2-a]pyrimidin-4-one (Example 1-69). LC / MS (ESI+) 102 m / z = 393.2 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 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-FLUQRO-3-IODO-8-METQXI-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1.2-A1PYRIMIDIN-4-ONE STEP 1: 3-FLUORO-4-METHOXYPIRIDIN-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 mmol) in DMSO (6 mL) was stirred for 10 h at 100 °C. The mixture was filtered, and the filtrate was purified directly by flash chromatography (C18 cartridge, 0.1% NH3 in water:ACN as eluent, 100% aqueous solution at 8:2) to give 3-fluoro-4-methoxypyridin-2-amine as a white solid (185 mg, 1.302 mmol, 67% yield). LC / MS (ESI+) m / z = 143.1 [M+H]+. STEP 2: 9-FLUORO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4ONA· 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 (ESP) m / z = 263.3 [M+H]+. STEP 3: 9-FLUORO-3-IODO-8-METHOXI-2-(TRIFLUOROMETHYL)-4H-PYRIDOri ,2A1PYRIMIDIN-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 9-fluoro-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESP) m / z = 388.9 [M+H]+. 103 INTERMEDIATE 3-L 3-BROMO-7-FLUORO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4ONE ii) H2O2, AcOH i) l DA. IHI. trimethylborate. Pdydbah Xanthphos K3PO4 Mel Ag2CO2 DCM Step 2 1.4 dioxane TFA DCM Step 4 Step 3 STEP 1: 2-CHLORO-5-FLUOROPYRIDIN-4-OL. To a solution of 2-chloro-5-fluoropyridine (11.6 mL, 114 mmol) in THF (120 mL) at -78 °C was added lithium diisopropylamide (2M in THF, 65 mL, 130 mmol) dropwise. The mixture was allowed to warm to -60° over 3 h, then the reaction was cooled to -78 °C and trimethyl borate (25.4 mL, 228 mmol) was added slowly. The temperature was slowly increased to 0 °C and the mixture was stirred for 2 h. 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 min. The reaction mixture was warmed to rt and then stirred overnight. Saturated aqueous sodium thiosulfate solution was added to the reaction, and the mixture was extracted with EtOAc (x2) and DCM (x2). The aqueous phase was acidified with 6M HCl solution to pH 5 / 6, and further extracted with EtOAc (x2) and DCM. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo.The resulting crude was washed by cleavage with DCM and the solid was collected to give 2-chloro-5-fluoropyridin-4-ol as a white solid (15.53 g, 105.3 mmol, 92% yield). LC / MS (ESP) m / z = 148.1 / 150.1 [M+H]+. STEP 2: 2-CHLORO-5-FLUORO-4-METHOXYPYRIDINE· To 2-chloro-5-fluoropyridin-4-ol (15.53 g, 105.3 mmol) in DCM (300 mL) were added silver carbonate (62.4 g, 224.64 mmol) and iodomethane (6.99 mL, 112.32 mmol), and the mixture was stirred at rt overnight. The mixture was filtered and the residue was washed with water (x2). The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. The residue was 104 was then purified by flash column chromatography (SO2, Cy:EtOAc as eluent, 100% Cy at 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 (ESI+) m / z = 161.9 / 163.9 [M+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 ether (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 min, then Pd2dba3 (2.88 g, 3.15 mmol) and (5-diphenylphosphino-9,9-dimethyl-4-xanthenyl)-diphenylphosphine (3.64 g, 6.3 mmol) were added, and the mixture was stirred at 100 °C for 15 h. The mixture was filtered, and the residue was concentrated in vacuo. The resulting material was purified by flash chromatography (Si2O, Cy:EtOAc as eluent, 100% Cy at 7:3) to give impure tert-butyl N-(5-fluoro-4-methoxypyridin-2-yl)carbamate which was used directly in the next reaction. LC / MS (ESI+) m / z = 187.3 [M-tBu+H]+. STEP 4: 5-FLUORO-4-METHOXYPIRIDIN-2-AMINE· To 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 rt overnight. The mixture was concentrated and the residue was loaded onto an SCX cartridge, washed with DCM and MeCN, and eluted with 10% ammonia in MeCN. The solvent was evaporated to give 5-fluoro-4-methoxypyridin-2-ylamine as a pale orange solid (2.16 g, 15.2 mmol). LC / MS (ESI+) m / z = 143.1 [M+H]+. STEP 5: 7-FLUORO-8-METHOXY-2-(TRIFLUOROMETHYL)PYRIDO[1.2-A1PYRIMIDIN-4-ONE· A mixture of 5-fluoro-4-methoxypyridine-2-amine (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 h. The mixture was partitioned between EtOAc and water, and the organic phase was dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude material was purified by flash chromatography (SiO2, DCM:MeOH as eluent, 100% DCM at 95:5) followed by flash reverse-phase chromatography (C18, 0.1% HCOOH solution in water:acetonitrile, 100% aqueous solution at 1:1) to give 7-fluoro-8-methoxy-2-(trifluoromethyl)pyrido[1,2-a]pyrimidine-4-one as a white solid (1.94 g, 7.41 mmol, 52% yield). LC / MS (ESI+) m / z = 263.1 [M+H]+. STEP 6: 3-BROMO-7-FLUORO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2A1PYRIMIDIN-4-ONE· A mixture of N-bromosuccinimide (1.45 g, 8.16 mmol) and 7-fluoro-8-methoxy-2-(trifulomethyl)pyrido[1,2-a]pyrimidin-4-one (1.94 g, 7.41 mmol) in MeCN (15 mL) was stirred at 80 °C for 1 h. The mixture was partitioned between EtOAc and water, and the organic phase was washed with sat. NaHCO3 and sat. Na2SO3. The organic phase was then dried over Na2SO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (SO2, Cy:EtOAc as eluent, 100% Cy to 7:3) to give 3-bromo-7-fluoro-8-methoxy-2-(trifluoromethyl) 105 4H-pyrido[1,2-a]pyrimidine-4-one as a white solid (2.53 g, 7.40 mmol, quantitative yield). LC / MS (ESI+) m / z = 341.1 / 343.1 [M+H]+. INTERMEDIATE 3-M 3-BROMO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIMIDOri,2-B1PYRIDAZIN-4-ONE NBS MeCN Step 4 TFA DCM Passed ? PASO1: N-(5-METOXIPIRIDAZIN-3-IL)CARBAMATO DE TERT-BUTILO. A solution of 3-chloro-5-methoxypyridazine (250 mg, 1.73 mmol, Combi-Blocks Inc.), carbamic acid di-butyl ester (263 mg, 2.25 mmol), and cesium carbonate (794 mg, 2.42 mmol) in 1,4-dioxane (5 mL) was degassed under a stream of nitrogen for 10 minutes, then (5-diphenylphosphino-9,9-dimethyl-4-xanthenyl)-diphenylphosphine (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 in vacuo. The resulting material was purified by flash chromatography (SO2, Cy:EtOAc as eluent, 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 (ESI+) m / z = 226.2 [M+H]+.1H NMR (400 MHz, CDCl3) δ 8.86 (d, J=2.6Hz, 1H), 8.59 (d, J=2.7Hz, 1H), 7.75 (d, J=2.7Hz, 1H), 7.66 (s, 1H), 6.96 (d, J=2.6Hz, 1H), 3.96 (s, 1H), 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 crude material which was purified by SCX cartridge to give 5-methoxypyridazin-3-amine as a white solid. (60 mg, 0.480 mmol, 68% yield). LC / MS (ESI+) m / z = 126.2 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J=2.6Hz, 1H), 6.22 (d, J=2.7Hz, 3H), 3.78 (s, 3H). Rczocn / zznz / q / υιλι 106 STEP 3: 8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIMIDOri.2-B1PYRIDAZIN-4-ONE· A mixture of 5-methoxypyridazin-3-amine (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 with Na2SO4, filtered and concentrated in vacuo to give a crude material which was purified by flash chromatography (SO2, Cy:EtOAc as eluent, 80:20 to 100% EtOAc) to give 8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2-b]pyridazin-4-one as a pale yellow solid (80 mg, 0.33 mmol, 48% yield). LC / MS (ESP) m / z = 246.1 [M+H]+.1H NMR (400 MHz, DMSO-de) δ 8.80 (d, J=2.9Hz, 1H), 7.58 (d, J=2.9Hz, 1H), 6.83 (s, 1H), 4.05 (s, 3H). Step 4: 3-bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrimidori,2-b1pyridazin-4-one. A mixture of 8-methoxy-2-(trifluoromethyl)pyrimido[1,2-b]pyridazin-4-one (95 mg, 0.390 mmol) and 1-bromopyrrolidine-2,5-dione (103 mg, 0.58 mmol) in MeCN (3 mL) was stirred at room temperature for 18 h and at 80 °C for 1 h. The mixture was concentrated, dissolved in DCM, and subsequently washed with saturated aqueous Na2S2O3 and NaHCO3 solutions, and brine. The organic phase was dried and concentrated to give 3-bromo-8-methoxy-2(trifluoromethyl)-4H-pyrimido[1,2-b]pyridazin-4-one as a yellow solid (112 mg, 0.346 mmol, 89% yield). LC / MS (ESP) m / z = 324.0 / 326.0 [M+H] + / - 1H NMR (400 MHz, DMSO-d6) δ 8.87 (d, J=2.8Hz, 1H), 7.61 (d, J=2.8Hz, 1H), 4.06 (s, 3H). INTERMEDIATE 3-N 3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDOÍ1,2-A1PYRIMIDIN-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 the mixture was stirred at 70 °C for 4 h, then the solvent was 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[1,2-a]pyrimidin-4-one (Intermediate 3-I, 100 mg, 0.24 mmol) and palladium triphenylphosphine (28 mg, 0.02 mmol) were added, and the mixture was stirred at 90 °C overnight. After cooling, the mixture was diluted with EtOAc and washed with water. The organic phase was dried and evaporated, and the crude was purified by flash chromatography (SO2, Cy / EtOAc 50:50) to afford 3-iodo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one as a yellow solid (62 mg, 0.182 mmol, 77% yield). LC / MS (ESP) m / z = 431.0 [M+H]+. 107 INTERMEDIATE 3-0 3-BROMO-7-METHOXI-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONE OO Br I F1 STEP 1: 7-METHOXI-2-(TRIFLUOROMETHYL)-4H-PYRIDON,2-A1PYRIMIDIN-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 sat. aq. NaHCO3 (80 mL) at 0 °C and the pH was adjusted to 7. The aqueous phase was then extracted with AcOEt (3 x 100 mL). The organic phase was dried with Na2SO4, filtered and concentrated in vacuo to give a crude material which was purified by flash chromatography (SO2, Cy:EtOAc 90:10 to 80:20) to give 7-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one as a pale yellow solid (1.66 g, 6.78 mmol, 84% yield). LC / MS (ESI+) m / z = 254.2 [M+H]+.1H NMR (400 MHz, CDCI3) δ 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-(TRIFLUOROMETHYL)-4H-PYRIDO[1.2-A1PYRIMIDIN-4-ONE· A mixture of 7-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-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. The mixture was concentrated, dissolved in DCM, and subsequently washed with saturated aqueous Na2S2O3 and NaHCO3 solutions, and brine. The organic phase was dried and the crude was purified by column chromatography (SiO2, Cy:EtOAc 9:1 to 6:4) to give 3-bromo-7-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a white solid (466 mg, 1.44 mmol, 88% yield). LC / MS (ESI+) m / z = 323.1 / 325.1 [M+H]+.1H NMR (400 MHz, CDCl3) δ 4.02 (s, 3H) 7.70 (dd, 1H) 7.80 (d, 1H) 8.61 (d, J 1H). INTERMEDIATE 3-P 3-BROMINE-8-(2-HYDROXYPROPAN-2-IL)-2-(TRIFLUOROMETHYL)-4H-PYRIDOM,2A1PYRIMIDIN-4-ONE 108 STEP 1: 8-(2-HYDROXYPROPAN-2-IL)-2-(TRIFLUOROMETHYL)-4H-PYRIDOÍ1.2-A1PYRIMIDIN4-ONE. A mixture of 2-(2-aminopyridine-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 h. The mixture was diluted with water and extracted with EtOAc twice. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo to give crude material which was purified by flash chromatography (SO2, Cy:EtOAc as eluent, 80:20 to 100% EtOAc) to give 8-(2-hydroxypropan-2-yl)-2(trifulomethyl)-4H-pyrido[1,2-a]pyrimid¡n-4-one (284 mg, 1.04 mmol, 19% yield). LC / MS (ESP) m / z = 273.1 [M+H]+. STEP 2: 3-BROMO-8-(2-HYDROXYPROPAN-2-IL)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2A1PYRIMIDIN-4-ONE· A mixture of 8-(2-hydroxypropan-2-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-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 h. The mixture was concentrated, dissolved in DCM, and subsequently washed with saturated aqueous Na2S2O3 and NaHCO3 solutions, and brine. The organic phase was dried and concentrated to give 3-bromo-8-(2-hydroxypropan-2-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a yellow solid (335 mg, 0.95 mmol, 91% yield). LC / MS (ESI+) m / z = 381.1 / 383.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 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-BROMINE-7-CHLORINE-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE STEP 1: 7-CHLORO-2-(TRIFLUOROMETHYL)-4H-PYRIDOri .2-A1PYRIMIDIN-4-ONE· A mixture of 2-amino-5-chloropyridine (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 h. MeOH was added, and the precipitate was vacuum filtered to give 7-chloro-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a pale yellow solid (753 mg, 3.03 mmol, 31% yield). LC / MS (ESP) m / z = 249.1 / 251.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 9.04 (d, J=2.3Hz, 1H), 8.20 (dd, J=9.5, 2.4Hz, 1H), 7.92 (dd, J=9.5, 0.7Hz, 1H), 6.93 (s, 1H). 109 STEP 2: 3-BROMINE-7-CHLORINE-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1.2-A1PYRIMIDIN-4-ONE· A mixture of 7-chloro-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (753 mg, 3 mmol) and N-bromosuccinimide (800 mg, 4.5 mmol) in MeCN (20 mL) was stirred at 80 °C for 6 h. The mixture was concentrated, dissolved in DCM, and subsequently washed with saturated aqueous Na2S2O3 and NaHCO3 solutions, and brine. The organic phase was dried and concentrated to give 3-bromo-7-chloro-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a yellow solid (989 mg, 3.02 mmol, quantitative yield). LC / MS (ESI+) m / z = 327.0 / 329.0 [M+HJ+. Ή NMR (400 MHz, DMSO-d6) δ 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-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE STEP 1: 8-(METHOXYMETHYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-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, the mixture was diluted with EtOAc and washed with water. The organic phase was dried and evaporated, and the crude was purified by flash chromatography (SO, Cy / EtOAc 1:1) to give 8-(methoxymethyl)-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (70 mg, 0.27 mmol, 37% yield). 1H NMR (400 MHz, CDCl) δ 9.07 (d, 1H), 7.79 (cd, 1H), 7.26 (dd, 1H), 6.78 (s, 1H), 4.62 (d, 2H), 3.53 (s, 3H). STEP 2: 3-BROMO-8-(METHOXYMETHYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN4-ONE· To A8-(methoxymethyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (70 mg, 0.27 mmol) in MeCN (3 mL) was added N-bromosuccinimide (53 mg, 0.30 mmol) and the mixture was stirred at RT for 3 h. The mixture was concentrated, diluted with EtOAc, and subsequently washed with Na2SO2Os and NaHCO3. The organic extracts were combined, dried, and evaporated to afford 3-bromo-8-(methoxymethyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one as a yellow solid (84 mg, 0.25 mmol, 92% yield). LC / MS (ESI+) m / z = 327.0 / 329.0 [M+H]+.1H NMR (400 MHz, CDCI3) δ 9.09 (dd, 1H), 7.82 (cd, 1H), 7.32 (dd, 1H), 4.62 (d, 2H), 3.54 (s, 3H). Intermediates 3-S to 3-AF in Table 2 were prepared analogously to the preparation of Intermediate 3-R. 110 TABLE 2 Chemical Structure Name Starting reagents and LC / MS (ESP) conditions m / z 3-S o' Π“τ( 00 Π Π 3-bromo-8-methoxy-6-methyl- 2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one 4-methoxy-6-methylpyridin-2-amine (preparation described in patent application WO2014 / 153280) 337.1 / 339.1 [M+H]+ 3-T 0 3-bromo-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-7-carbonitrile 6-amino-3-pyridinecarbonitrile 318.1 / 320.1 [M+H]+ 3-U 0 'XíX FF 3-bromo-7-methoxy¡-2-(trifluoromethyl)4H-pyrimido[1,2b]pyridazin-4-one 6-methoxypyridazin-3-amine (preparation described in patent application WO2013 / 68458) 324.1 / 326.1 [M+H]+ 3-V 0 0 '“Cύς-, FF 3-bromo-4-oxo2-(trifluoromethyl)4H-pyrido[1,2a]pyr¡midine-7-carboxylic acid methyl ester 6-amino-3-pyridinecarboxylic acid methyl ester 351.2 / 353.2 [M+H]+ ficzQcn / zznz / q / υιλι 3-X 0 w, F r 3-bromo-7methyl-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4one 2-amino-5methylpyridine 307.1 / 309.1 [M+H]+ 3-Y 0 XíX; F r 3-bromo-7fluoro-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4one 2-amino-5fluoropyridine 311.0 / 313.0 [M+H]+ 3-Z 0 3-bromo-7methyl-2(trifluoromethyl)4H-pyrim¡do[1,2b]pyridazin-4one 3-amino-6methylpyridazine (Apollo Scientific Ltd) 308.0 / 310.0 [M+H]+ 3-AA o—< ÜO Π 3-bromo-2(trifluoromethyl)4H,6H,7H,9Hpyrimido[2,1c][1,4]oxazin-4one morpholin-3ylidenamine hydrochloride (prep described in patent application WO2003 / 93279) 299.0 / 301.0 [M+H]+ 3-AB 0 x*í, F r 3-bromo-8methyl-2(trifluoromethyl)4H-pyrimido[1,2b]pyridazin-4one 3-amino-5methylpyridazine (Apollo Scientific Ltd.); 307.9 / 309.9 [M+H]+ 112 Rczocn / zznz / q / υιλι 3-AC LL LL / \ / LL R U- O / 3-bromo-7fluoro-8-methoxy- 2(trifluoromethyl)4H[1,3]diazino[1,2a]pyrimidin-4one prepared from 2-chloro-5fluoro-4methoxypyrimidine (Apollo Scientific Ltd) such as described for Intermediate 3-M 341.9 / 343.9 [M+H]+ 3-AD OX*5,3-bromo-7,8dimethyl-2(trifluoromethyl)4H-pyrimido[1,2b]pyridazin-4one 5,6dimethylpyridazin-3amine (Enamine Ltd) 321.9 / 323.9 [M+H]+ 3-AE o 3-Bromo-7chloro-8-methyl-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4one 2-amino-5-chloro- 4-picoline (CombiBlocks Inc.) 340.9 / 342.9 [M+H]+ 3-AF or χύς-, F r 3-Bromo-7fluoro-8-methyl-2(trifluoromethyl)4H-pyrido[1,2a]pyrim¡d¡n-4one 2-Amino-5-fluoro- 4-picoline (CombiBlocks Inc) 325.0 / 327.0 [M+H]+ 113 INTERMEDIATE 4-A 3-BROMO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-RI,31DIAZINORI.6-A1PYRIMIDIN-4-ONA NaH trifluoroacetic anhydrous Step 1 Toluene Step 2 STEP 1: 2,2,2-TRIFLUORO-N-(6-METHOXYPYRIMIDIN-4-IL)ACETAMIDE· 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 1 h, trifluoroacetic anhydride (5.37 g, 25.57 mmol) was added and the mixture was allowed 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 Na2SO4 and evaporated in vacuo. The crude was purified by flash chromatography (SiO2, eluted with 100:0 to 75:25 cyclohexanes:EtOAc) to afford 2,2,2-trifluoro-N-(6-methoxypyrimidn-4-yl)acetamide (2.08 g, 9.41 mmol, 59% yield). LC / MS (ESI+) m / z = 222.3 [M+H]+.1H NMR (400 MHz, DMSOd6) δ 3.95 (s, 3H), 7.36 (s, 1H), 8.69 (s, 1H), 12.38 (bs, 1H). STEP 2: ETHYL 4A4-TRIFLUORO-3-r(6-METHOXYPIRIMIDIN-4-IL)AMINO1BUT-2-ENOATE. 2,2,2-Trifluoro-N-(6-methoxypyrimidine-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 allowed to react at room temperature for 2 h then at 55 °C for 3 h. The solvent was removed in vacuo and the crude product was purified by flash chromatography (SO2, eluted with cyclohexane:EtOAc 100:0 to 80:20) to give ethyl 4,4,4-trifluoro-3-[(6-methoxypyrimidine-4-yl)amino]but-2-enoate (671 mg, 2.30 mmol, 24.5% yield). LC / MS (ESI+) m / z = 292.3 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 1.03 (t, 3H) 3.87 (s, 3H) 3.95 (c, 2H) 6.16 (s, 1H) 6.25 (d, 1H) 8.30 (d, 1H) 9.55 (sa, 1H). STEP 3: 8-METHOXY-2-(TRIFLUOROMETHYL)-4H-ri.31ΡΙΑΖΙΝΟΓ1.6-A1PYRIMIDIN-4-ONA· Ethyl 4,4,4-trifluoro-3-[(6-methoxypyrimidin-4-yl)amino]but-2-enoate (671 mg, 2.30 mmol) was evaporated repeatedly at 60 °C from a mixture of water (70 mL) and MeCN (40 mL). The crude product was purified by flash chromatography (SiO2, cyclohexanes: EtOAc from 100:0 to 55:45 114 as eluent) to give 8-methoxy-2-(trifluoromethyl)-4H-[1,3]diazino[1,6-a]pyrimidin-4-one (300 mg, 1.22 mmol, 53% yield). LC / MS (ESP) m / z = 246.3 [M+H]+. STEP 4: 3-BROMO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-ri.31DIAZINOri,6-A1PYRIMIDIN-4ONE. A mixture of 8-methoxy-2-(trifluoromethyl)-4H-[1,3]diazino[1,6-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 subsequently washed with saturated aqueous Na2S2O3 and NaHCO3 solutions and brine. The organic phase was dried and concentrated to give the crude which was purified by flash chromatography (S1O2, cyclohexane:EtOAc from 100:0 to 50:50 as eluent) to give 3-bromo-8-methoxy2-(trifluoromethyl)-4H-[1,3]diazino[1,6-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]+.1H NMR (400 MHz, DMSO-d6) δ 4.07 (s, 3H) 7.13 (m,1H) 9.57-9.64 (m, 1H). Intermediates 4-B to 4-I in Table 3 were prepared analogously to the preparation of Intermediate 4-A. TABLE 3 N.° de Int. Estructura química Nombre Reactivos de partida y condiciones LC / MS (ESP) m / z 4-B LL LL / m χ \___ / LL 0 w θ' 3-bromo-7-metoxi2-(trifluorometil)4H[1,3]diazino[1,2a]pir¡m¡d¡n-4-ona 2-amino-5metoxipirimidina 324.0 / 326.0 [M+H]+ 4-CZ—Λ / / Ά z^o TL / \ / Π TI 3-bromo-2- (trifluorometil)-4Hpirazino[1,2a]pir¡m¡din-4-ona 2-aminopyrazine 294.0 / 296.0 [M+H]+ 4-D LL Í- LL / OD \ / LL 0 3-bromo-7-methyl-2(trifluoromethyl)-4Hpyrazino[1,2a]pinm¡din-4-ona 2-amino-5methylpyrazine (Apollo Scientific Ltd) 308.1 / 310.1 [M+H]+ 115 Rczocn / zznz / q / υιλι 4-E ll LL / CO \ / LL ,Z 0 O 3-bromo-7-cloro-2(trifluorometil)-4Hpirazino[1,2a]p¡r¡mid¡n-4-ona 2-amino-5cloropirazina (Combi-Blocks Inc.) 328.0 / 330.0 [M+H]+ 4-F LL LL / co X \___ / LL / Z 0 O\ 3-bromo-7-metoxi2-(trifluorometil)4H-pirazino[1,2a]pir¡m¡din-4-ona 2-amino-5metoxipirazina (Fluorochem Ltd.) 323.9 / 325.9 [M+H]+ 4-G LL í- LL / co \ / LL O=M 3-bromo-7-metil-2- (trifluorometil)-4H- [1,3]diazino[1,2a]pir¡m¡din-4-ona 2-amino-5metilpirimidina (Fluorochem Ltd.); nota: Paso 3 - Calentada hasta 225°C en éter difenílico 307.9 / 309.9 [M+H]+ 4-H 0 ¢0, 3-bromo-9-metil-2(trifluorometil)-4Hpirazino[1,2a]pir¡m¡din-4-ona 2-amino-3metilpirazina (Fluorochem Ltd) 308.0 / 310.0 [M+H]+ 4-I 0 w 3-bromo-7,9dimetil-2(tr¡fluorometil)-4Hpirazino[1,2a]pirim¡din-4-ona 2-amino-3,5dimetilpirazina (Combi-Blocks Inc) 322.0 / 324.0 [M+H]+ 116 INTERMEDIO 4-J 3-BROMO-7-CICLORROPIL-2-(TRIFLUOROMETIL)-4H-PIRIDOri.2-A1PIRIMIDIN-4-ONA Paso 1 NBS --► MeCN Step 3 STEP 1: 7-BROMO-2-(TRIFLUOROMETHYL)-4H-PYRIDON,2-A1PYRIMIDIN-4-ONA· 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 h. The reaction was then cooled to RT, diluted with a distilled water / brine mixture, and extracted with EtOAc. The organic phase was then washed with brine (x2) and concentrated in vacuo. The mixture was purified by flash chromatography (SO2, EtOAc:Cy from 3:97 to 25:75) followed by flash reverse-phase chromatography (C18, H2O + 0.1% HCOOH:MeCN from 97:3 to 40:60) to afford 7-bromo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one as a white solid (517 mg, 1.76 mmol, 24% yield). LC / MS (ESI+) m / z = 293.0 / 295.0 [M+H]+. STEP 2: 7-CYCLOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONE. A mixture of 7-bromo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimdin-4-one (150 mg, 0.51 mmol), palladium triphenylphosphine (592 mg, 0.51 mmol), cyclopropylboronic acid (44 mg, 0.51 mmol), and potassium carbonate (71 mg, 0.51 mmol) was suspended in dry toluene (3 mL) and placed in a sealable vial. It was degassed with several cycles of vacuum / nitrogen, then stirred and heated at 100 °C for 18 h. The mixture was cooled to RT, diluted with EtOAc, and washed with distilled water and brine. The organic phase was dried over Na2SO4 and concentrated in vacuo. The mixture was then purified by flash chromatography (S1O2, EtOAc:Cy 3:97 to 30:70) to afford 7-cyclopropyl-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a white solid. (110 mg, 0.43 mmol, 85% yield). LC / MS (ESI+) m / z = 255.1 [M+H]+. STEP 3: 3-BROMO-7-CYCLOPROPYL-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-AIPIRIMIDIN4-ONE· A mixture of 7-cyclopropyl-2-(trifluoromethyl)pyrido[1,2-a]pyrimidine-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. The mixture was diluted with DCM, and subsequently washed with 117 Saturated aqueous Na2S2O3 and brine. The mixture was purified by flash chromatography (SI02, EtOAc:Cy 3:97 to 25:75) to afford 3-bromo-7-cyclopropyl-2-(trifluoromethyl)-4-Hpyrido[1,2-a]pyrimidine-4-one as a white solid (130 mg, 0.39 mmol, 90% yield). LC / MS (ESP) m / z = 333.1 / 335.1 [M+H]+. INTERMEDIATE 4-K 7-(AZETIDIN-1-IL)-3-BROMO-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE azetidine Or Pd(OAc)2 Br _U Xantphos OV Cs?CO3 1,4 dioxane MeCN F Pasol Tf Paso? I STEP 1: 7-(AZETIDIN-1-IL)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE· 7-Bromo-2-(trifluoromethyl)-4H-pyrido[1,2a]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) were placed in a screw-capped vial. The mixture was stirred at 100 °C in a screw-capped vial for 4 h, then cooled 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 (SiO2,Cy:EtOAc from 95:5 to 60:40) followed by flash reverse phase chromatography (C18, H2O + 0.1% HCOOH:MeCN from 97:3 to 50:50) to give 7-(azetidin-1-yl)-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one as a yellow solid (35 mg, 0.13 mmol, 63% yield). LC / MS (ESP) m / z 270.1 [M+H]+. STEP 2: 7-(AZETIDIN-1-IL)-3-BROMO-2-(TRIFLUOROMETHYL)-4H-PYRIDIN,2-A1PYRIMIDIN4-ONE. A mixture of 7-(azetidin-1-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-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, and subsequently washed with saturated aqueous Na2S2O3 and NaHCO3. The organic phase was dried and concentrated in vacuo. The mixture was purified by reverse phase chromatography (C18, H2O + 0.1% HCOOH:MeCN from 97:3 to 50:50) to give 7-(azetidin-1-yl)-3-bromo-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a yellow solid (18 mg, 0.052 mmol, 40% yield). LC / MS (ESP) m / z = 348.0 / 350.0 [M+H]+. 118 INTERMEDIATE 4-L 3-BROMO-7-(METHOXYMETHYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONE EITHER NBS >) --► MeCN Step 3 STEP 1: 7-(BROMOMETHYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE· A suspension of 7-methyl-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one (Intermediate 3-X, Step 1, 500 mg, 2.19 mmol), N-bromosuccinimide (585 mg, 3.29 mmol) and 2,2'-azobis(2-methylpropionitrile) (36 mg, 0.220 mmol) in carbon tetrachloride (10 mL) was stirred at 80 °C for 7 h. The mixture was evaporated and the crude was purified by flash chromatography (SO2, Cy / EtOAc 100:0 to 70:30) to give 7-(bromomethyl)-2-(t-fluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (130 mg, 0.423 mmol, 19% yield). LC / MS (ESI+) m / z = 307.0 / 309.0 [M+H]+. STEP 2: 7-(METHOXYMETHYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE· To a suspension of 7-(bromomethyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (60 mg, 0.20 mmol) in methanol (4 mL) was added sodium methoxide (11.6 mg, 0.21 mmol) and the mixture was stirred at rt for 3 days. The mixture was evaporated and the crude was purified by flash chromatography (SO, Cy / EtOAc 100:0 to 70:30) to afford 7-(methoxymethyl)-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one as a white solid (34 mg, 0.132 mmol, 67% yield). LC / MS (ESI+) m / z = 259.1 [M+H]+. STEP 3: 3-BROMO-7-(METHOXYMETHYL)-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-AIPIRIMIDIN4-ONE· To a solution of 7-(methoxymethyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (34 mg, 0.13 mmol) in MeCN (3 mL) was added N-bromosuccinimide (26 mg, 0.14 mmol) and the mixture was stirred at rt for 18 h. The mixture was concentrated, diluted with EtOAc, and washed with Na2SO2O and NaHCO3. The organic phases were combined, dried, and evaporated to give -bromo-7-(methoxymethyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (35 mg, 0.104 mmol, 79% yield). LC / MS (ESI+) m / z = 337.0 / 339.0 [M+H]+. 119 INTERMEDIATE 4-M 3-BROMO-7-r(DIMETHYLAMINO)METHYL1-2-(TRIFLUOROMETHYL)-4H-PYRIDON,2-A1RIRIMIDIN4-ONE STEP 1: 3-BROMO-7-r(DIMETHYLAMINO)METHYL1-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2A1PYRIMIDIN-4-ONE· A solution of 3-bromo-7-methyl-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-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 stirred at rt for 2 h, then heated to 80 °C and stirred at that temperature for 24 h. The mixture was evaporated and the crude was purified by flash chromatography (SO2, Cy / EtOAc 100:0 to 70:30) to afford 3-bromo-7-(bromomethyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one as a pale yellow solid (15.5 mg, 0.040 mmol, 46% yield). LC / MS (ESI+) m / z = 387.1 [M+H]+. STEP 2: 3-BROMO-7-r(DIMETHYLAMINO)METHYL1-2-(TRIFLUOROMETHYL)-4H-PYRIDON,2A1PYRIMIDIN-4-ONE. To a solution of 3-bromo-7-(bromomethyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-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 1 h. The mixture was evaporated to give 3-bromo-7-[(dimethylamino)methyl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one which was used directly in the next step. LC / MS (ESI+) m / z = 350.2 / 352.2 [M+H]+. INTERMEDIATE 4-N 8-METHOXY-3-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-2-(TRIFLUOROMETHYL)4H-PYRIDOri .2-A1PYRIMIDIN-4-ONE STEP 1: 8-METHOXI-3-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-2(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE. 3-Bromo-8-methox¡-2-(trifluoromethyl)-4H-pyr¡do[1,2-a]pyrim¡din-4-one (Intermediate 1-A, 0.5 g, 1.55 mmol), bis(pinacolato)diboron (0.51 g, 2.01 mmol), bis(pinacolato)d¡boron (0.51 g, 2.01 mmol), 120 potassium chloride (0.41 g, 4.18 mmol) and [1,1'-bis(dphenylphosphino)ferrocene]dichloropalladium(II) complex with DCM (63.4 mg, 0.08 mmol) in a microwave vial in toluene (10.0 mL), and degassed for 10 minutes. The tube was sealed and the reaction was stirred at 130 °C for 3 hours under microwave irradiation. After this time, the mixture was diluted with EtOAc, washed with water, dried and removed. The residue was purified by flash chromatography (SiO2, cyclohexane:EtOAc) to give 8-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (30 mg, 0.08 mmol, 5% yield). LC / MS (ESP) m / z = 371.4 [M+H]+. INTERMEDIATE 4-0 3-BROMINE-2-ETHOXY-8-METHOXYPYRIDONE,2-A1PYRIMIDIN-4-ONE STEP 1: 2-HYDROXY-8-METHOXYPYRIDOri .2-A1PYRIMIDIN-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 a nitrogen atmosphere and the reaction was allowed to stir at room temperature for 48 h. After this time, the reaction was filtered, washed with DCM, the organic phase was dried and evaporated. The crude material was used as is in the next reaction. STEP 2: 2-ETHOXY-8-METHOXYPYRIDOri,2-A1PYRIMIDIN-4-ONE· The crude 2-hydroxy-8-methoxypyrido[1,2-a]pyrimidin-4-one obtained in 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. Iodoethane (0.09 mL, 1.09 mmol) was added, and the reaction was stirred at 65 °C overnight. Water was added, and the mixture was extracted with EtOAc. The organic phase was dried and removed. The crude product was purified by flash chromatography (SO2, cyclohexane:EtOAc) to afford 2-ethoxy-8-methoxypyrido[1,2-a]pyrimidin-4-one (102 mg, 0.46 mmol, 44% yield). LC / MS (ESP) m / z = 221.3 [M+H]+. STEP 3: 3-BROMO-2-ETHOXY-8-METHOXYPYRIDOri,2-A1PYRIMIDIN-4-ONE· 2-Ethoxy-8-methoxypyrido[1,2-a]pyrimidine-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 mixture was stirred at 20°C. 121 room temperature overnight. After this time, the solvent was removed and the crude product was purified by flash chromatography (S102, cyclohexane:EtOAc) to afford 3-bromo-2-ethoxy-8-methoxypyrido[1,2-a]pinmdin-4-one (44.0 mg, 0.15 mmol, 31% yield). LC / MS (ESP) m / z = 301.0 / 302.0 [M+H]+. INTERMEDIATE 4-P 3-BROMINE-1-(2,2,3,3,3-PENTAFLUOROPROPYL)-1,2,4-TRIAZOLE Br Cs2CO3, MeCN V F3C ' O cf3 3-Bromo-1 H-1,2,4-triazole (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 h. The mixture was concentrated in vacuo, 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)-1,2,4-triazole (865 mg, 3.09 mmol, 91% yield).1H NMR (500 MHz, DMSO-d6) δ 5.41 (t, J=15.23 Ηζ, 2H), 8.75 (s, 1H). INTERMEDIATE 4-Q [2-(2,2,2-TRIFLUOROETHOXY)PYRIMIDIN-5-IL1BORONIC ACID bis(pinacolato)diboron Step 1 Pd(dppf)CI2.DCM KOAc ----► HO 1,4 dioxane Step 2 PAS01: 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 0 °C was added 60% sodium hydride (0.31 g, 7.75 mmol). The mixture was allowed to reach rt in 15 min, then 5-bromo-2-chloropyrimidine (1.0 g, 5.17 mmol) was added. The mixture was stirred at room temperature for 2 h. EtOAc and brine were added, the layers were separated, the organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (SO2, Cy / EtOAc 95 / 5) to give 5-bromo-2-(2,2,2-trifluoroethoxy)pyrimidine as a colorless oil. (893 mg, 3.47 mmol, 67% yield). LC / MS (ESP) m / z = 257.1 / 259.1 [M+H]+. 122 STEP^íACIDJ^^^^J^IFLUOROETHIOlF^^ To a solution of 5-bromo-2-(2,2,2-trifluoroethoxy)pyrimidine (0.89 g, 3.46 mmol) in 1,4dioxane (10 mL) were added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)1,3,2-dioxaborolane (1.32 g, 5.19 mmol), potassium acetate (1030 mg, 10.39 mmol) and [1 ,T-bis(diphenylphosphino)ferrocene]dichloropalladium(ll), complex with dichloromethane (142 mg, 0.170 mmol). The mixture was degassed for 10 minutes, then stirred at 90 °C for 3 h. Concentrated and purified by flash chromatography (C18, H2O+0.1% HCOOH / CH3CN 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).1H NMR (400 MHz, DMSO-d) δ 4.97-5.00 (m, 1H) 5.06 (q, J=8.95 Hz, 2H) 8.52 (s, 2H) 8.89 (s, 2H). INTERMEDIATE 4-R f2-(2,2,3,3,3-PENTAFLUOROPROPOXY)PYRIMIDIN-5-YL1BORONIC ACID 7,7.3,3,3 bis(pinacolato)diboron pcntafluoropropanolF FPd(dppf)CI2.DCMNal* KOAc ()Mf N PF1,4dioxaneH°'B Step θΓStep 7 H The title 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-1-ol. Step 1 LC / MS (ESI+) m / z = 307.1 / 309.1 [M+H]+. Step 2 LC / MS (ESI+) m / z = 273.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 5.16 (t, J=13.20 Hz, 2H) 8.47 - 8.55 (m, 2H) 8.89 (s, 2H). INTERMEDIATE 4-S TRIFLUORO-[1-(2,2,3,3,3-PENTAFLUOROPROPYL)PYRAZOLE-4-IL1BOROHYDRIDE STEP 1: TRIFLUORO-ri-(2,2,3,3,3-PENTAFLUOROPROPYL)PYRAZOLE-4IL1POTASSIUM BOROHYDRIDE· A mixture of 1-(2,2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-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 2 h. The solvent was evaporated, the residue was suspended in hot acetone (25 mL) and filtered to remove undissolved salts. The solvent was evaporated, the residue was redissolved in hot acetone, cooled 123 Rczocn / zznz / q / uyl to rt and allowed to stand overnight. The crystallized product was collected, washed with cold acetone, and dried in vacuo to give potassium trifluoro-[1-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]borohydride (270 mg, 0.88 mmol, 29% yield). 1H NMR (400 MHz, DMSO) δ 4.98 (t, J=15.30 Hz, 2H), 7.03-7.33 (m, 2H). INTERMEDIATE 4-T 1-[(2,2-DIFLUOROCYCLOPROPYL)METHYL1-4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN2-IL)PYRAZOLE STEP 1: 1 -r(2,2-DIFLUOROCYCLOPROPIL)METHYL1-4-(4,4,5,5-TETRAMETHYL-1,3,2DIOXABOROLAN-2-IL)PYRAZOLE· 4-Pyrazoleboronic acid pinacolic 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) were placed in a resealable vial. The reaction mixture was heated at 80 °C for 4 h, then cooled to rt and filtered, washing with MeCN. The filtrate was concentrated under reduced pressure and purified by flash chromatography (SO, 0-50% EtOAc / cyclohexane) to afford 1-[(2,2-difluorocyclopropyl)methyl]-4-(4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl)pyrazole (460 mg, 1.62 mmol, 31% yield) as a colorless oil. LC / MS (ESP) m / z = 285.2 [M+H]+. INTERMEDIATE 4-U 1-(CYCLOPROPYLMETHYL)-4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)-1HPYRAZOLE STEP 1: 1 -(CYCLOPROPYLMETHYL)-4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)1H-PYRAZOLE. Cyclopropanemethanol (0.89 g, 12.37 mmol) was added dropwise to a stirred solution of 4-pyrazoleboronic acid pinacolic 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 a nitrogen atmosphere at 0 °C. The mixture The reaction mixture was allowed to warm to rt and stirred for 24 h. The mixture was concentrated under reduced pressure, cyclohexane was added, and the resulting precipitate was filtered off. The filtrate was evaporated and the crude product was purified by flash chromatography (SI02, 0-50% EtOAc / cyclohexane) to afford 1-(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 (ESP) m / z = 249.1 [M+H]+. INTERMEDIATE 4-V 1-[(3,3-DIFLUOROCYCLOBUTYL)METHYL1-4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2IDPIRAZOLE STEP 1: 1-n3,3-DIFLUOROCYCLOBUTIL)METHYL1-4-(4,4,5,5-TETRAMETHYL-1,3,2DIOXABOROLAN-2-IL)PYRAZOLE. A solution of 3-(bromomethyl)-1,1-difluorocyclobutane (195 mg, 1.05 mmol) in DMF (0.6 mL) was added to a stirred suspension of 4-pyrazoleboronic acid pinacolic ester (200 mg, 1.03 mmol) and cesium carbonate (537 mg, 1.65 mmol) in DMF (1.4 mL) at 0 °C. The reaction mixture was stirred at rt for 18 h, then filtered, washing with EtOAc. The filtrate was washed with brine (2x), dried over Na2SO4, filtered, and concentrated under reduced pressure to afford 1-[(3,3-difluorocyclobutyl)methyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole as a colorless oil. (270 mg, 0.9 mmol, 88% yield). LC / MS (ESP) m / z = 299.1 [M+H]+. INTERMEDIATE 4-W 4,4,5,5-TETRAMETHYL-2-í4-(2.2.2-TRIFLUOROETHOXY)PHENYL1-1.3,2-DIOXABOROLANE 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, 125 289 mmol) in DMF (80 mL) at 0 °C. The reaction mixture was heated at 110 °C for 16 h. 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 (SiO2, 50% EtOAc / cyclohexane) afforded 1-bromo-4-(2,2,2-trifluoroethoxy)benzene (10.9 g, 42.73 mmol, 74% yield). 1H NMR (400 MHz, DMSOd6) δ 4.78 (c, J=8.88 Hz, 2H), 7.02-7.08 (m, 2H), 7.48-7.56 (m, 2H). STEP 2: 4,4,5,5-TETRAMETHYL-2-[4-(2,2,2-TRIFLUOROETHOXY)PHENYL1-1,3,2DIOXABOROLANE. A mixture of 1-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 [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (719 mg, 0.98 mmol) in 1,4-dioxane (50 mL) was degassed with nitrogen for 5 min, then heated at 110 °C for 4 h. After cooling to rt, the mixture was filtered with EtOAc through a pad of celite. The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography (SiO2, 0-3% EtOAc / cyclohexane) to give 4,4,5,5-tetramethyl-2-[4-(2,2,2-trifluoroethoxy)phenyl]-1,3,2-dioxaborolane (2.76 g, 9.13 mmol, 47% yield) as a colorless oil. LC / MS (ESI+) m / z = 303.1 [M+H]+. INTERMEDIATE 4-X 1-(OXETAN-3-YLMETHYL)-4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)PYRAZOLE Step 1: 1 -(oxetan-3-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole· 4-Pyrazolboronic acid pinacolic 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) were placed in a microwave-safe vial. The 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 (SO2, 50-90% EtOAc / cyclohexane) to give 1-(oxetan-3-ylmethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (270 mg, 1 mmol, 100% yield) as a brown oil. LC / MS (ESI+) m / z = 265.0 [M+H]+. 126 INTERMEDIATE 4-Y 1-(2,2,3,3,3-PENTAFLUOROPROPYL)-3-(4,4,5,5-TETRAMETHYL-1,3.2-DIOXABOROLAN-2IDPYRAZOLE STEP 1: 1 -(2,2,3,3,3-PENTAFLUOROPROPYL)-3-(4,4,5,5-TETRAMETHYL-1,3,2DIOXABOROLAN-2-IL)PYRAZOLE. 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-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 trifluoromethanesulfonate (1.32 mL, 7.99 mmol) were placed in a resealable vial. The mixture was heated at 80 °C for 20 h, then cooled to rt, and partitioned between water and EtOAc. The organic phases were dried with Na2SO4, filtered and evaporated under reduced pressure to give 1-(2,2,3,3,3-pentafluoropropyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole (1 g, 3.07 mmol, 60% yield) which was used in the next reaction without further purification. LC / MS (ESP) m / z = 327.2 [M+H]+. INTERMEDIATE 4-Z 9-CHLORINE-3-IODINE-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE STEP 1: 9-CHLORO-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-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-chloro-4-methoxypyridin-2-amine (preparation described in WO2017197555). LC / MS (ESP) m / z = 279.0 / 281.0 [M+H]+. STEP 2: 9-CHLORINE-3-IODINE-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDori,2A1PYRIMIDIN-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 9-chloro-8-methoxy2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one. LC / MS (ESP) m / z = 404.9 / 406.9 [M+H]+. 127 SUMMARY OF EXAMPLES: METHOD 1 EXAMPLE 1-1: 3-(4-(8-METHOXY-4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDO1,2-A1PYRIMIDIN- Cs2CO}, dioxane Pasoi STEP 1: 3-(4-(8-METHOXI-4-OXO-2-(TRIFLUOROMETHYL)-4H-PYRIDORi ,2-A1PYRIMIDIN-3IL)PHENYL)PROPANONITRIL. 3-Bromo-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one (Intermediate 1-A, 170 mg, 0.526 mmol), 4-(2-cyanoethyl)phenylboronic acid (138 mg, 0.789 mmol, Combi-Blocks Inc.), tns(dbenzylideneacetone)dpalladium(O) (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) were placed in a resealable vial. The vial was evacuated and filled with nitrogen. This procedure was repeated 3 times, after to which 1,4-dioxane (850 µl) was added. The reaction mixture was heated to 90 °C and stirred for 12 h. The reaction mixture was quenched with water (2 mL) and diluted with EtOAc (2 mL). The 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.The crude product was purified by silica gel chromatography (eluent: 0-70% EtOAc / heptane) to afford 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)4H-pyrido[1,2-a]pyrimidin-3-yl)phenyl)propanenitrile as a white solid. LC / MS (ESl·) m / z = 374.0 [M+H]+.1H NMR (400 MHz, CD2CI2) δ 2.70 (t, J=7.57 Hz, 2H) 3.03 (t, J=7.46 Hz, 2H) 4.03 (s, 3H) 6.86 - 7.01 (m, 1H) 7.05 (d, J=2.70 Hz, 1H) 7.23 - 7.40 (m, 4H) 8.91 (d, J=7.88 Hz, 1H). Examples 1-2 through 1-88 listed in Table 4 were prepared following the procedure described in Method 1, Step 1, above as follows. TABLE 4 Ex. No. Chemical Structure Name Reagent and Method Changes 128 RC7QCn / 77n7 / q / YIL 1-2 °=\ ,zo— (4-(8-methoxy-4oxo-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-3yl)phenyl)aceton¡tryl (4(cyanomethyl)phenyl)boronic acid (Combi-Blocks Inc.) 1-3 0 r=\ / =^ xx AA 'N~^ / ) ÁA K / 0 NFF 8-methox¡-3-(1phenyl-1 H-pyrazol-3yl)-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 1-Phenyl-3-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1 Hpirazole (Essen Scientific) 1-4 io Q. o— 3-(4-((2,2difluorocyclopropyl )methoxy)phenyl)-8methoxy¡-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 2-[4-[(2,2difluorocyclopropyl)methoxy¡]phe nil]-4,4,5,5-tetramethyl-1,3,2dioxaborolan (Intermediate 2-A) 1-5 A i^n AAA / FF 8-methox¡-3-(3phenyl-1,2-oxazol5-yl)-2(trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one 3-Phenyl-5-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1 Hysoxazole (Essen Scientific) 1-6 x¿4^ IFF 8-Methox¡-3-(2phenyl-1,3-oxazol5-yl)-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 2-Phenyl-5-(4,4,5,5-tetramethyl1,3,2-dioxaborolan-2yl)oxazole (Intermediate 2-B); 129 Rczocn / zznz / q / υιλι1-7 o— 3-(1-benzofuran2-¡l)-8-methoxy-2(trifluoromethyl)4H-pyrido[1,2a]pyrim¡d¡n-4-one 3-yodo-8-methoxy-2(tr¡fluoromethyl)pyrido[1,2a]pyrimid¡n-4-one (Intermediate 1-B), acid benzo[b]furan-2-boronic (Alfa Aesar) 1-8 ¥ o— 3-(4(cyclopropylmethoxy)phenyl)-8-methoxy-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 3-yodo-8-methoxy-2-(trifl uoromethyl)pyrido[1,2a]pyrim¡d¡n-4-one (Intermediate 1-B), [4(cyclopropylmethoxy)phen¡l]boranodiol (Combi-Blocks Inc.) 1-9 —oz / =° 3-(2-fluoro-4(trifluoromethoxy)phenyl)-8-methoxy-2(trifluoromethyl)4H-pyrido[1,2a]pyrim¡d¡n-4-one 2-fluoro-4trifluoromethoxyphenylboronic acid (Combi-Blocks Inc.) 1- 10 F χχϊ^ MeO'^^^^N'^'CFa 3-(4-(2,2difluoroethoxy)phenyl)-8-methoxy-2(trifluoromethyl)4H-pyrido[1,2a]pyrim¡din-4-one 2-(4-(2,2-difluoroethoxy)phenyl)4,4,5,5-tetramethyl-1,3,2dioxaborolane (Intermediate 2-C) 1- 11 NFF 3-(4-(2fluoroethoxy)phenyl)8-methox¡-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 4-(2fluoroethoxy)phenylboronic acid (Combi-Blocks Inc.) 1- 12 O > oo / 2-(difluoromethyl)3-(3-fluoro-4(2,2,2trifluoroethoxy)phenyl) -8-methoxy-4H- 3-bromo-2-(difluoromethyl)-8methoxy-pyrido[1,2-a]pi 1-one (midi n4) intermediate; 3-fluoro-4-(2,2,2-) acid. 130 RC7QCn / 77n7 / q / ΥΙΛΙ pyrido[1,2a]pyrim¡din-4-one trifluoroethoxy)benzeneboron¡ co (Combi-Blocks Inc.) 1- 13 „ ,N. .O. .CF, 1ΧΓ 0 Ν F. 2-(difluoromethyl)8-methox¡-3-(6(2,2,2trifluoroethoxy)-3pyridinyl)-4Hpyrido[1,2a]pyrimidin-4-one 3-bromo-2-(difluoromethyl)-8methoxy-p¡rido[1,2-a]pi ri midi n4-one (Intermediate 1-C); [6-(2,2,2tnfluoroethoxy)pyr¡d¡n-3yl]boronic (Combi-Blocks Inc.) 1- 14 cf3 0 / Τ Π jl / Ν II F 2-(difluoromethyl)8-methox¡-3-(1(3,3,3trifluoropropyl)1 H-pyrazol-4-yl)4H-pyrido[1,2a]pyrimid¡n-4-one 3-bromo-2-(difluoromethyl)-8methoxy-pyr¡do[1,2-a]pi rim id i n4-one (Intermediate 1-C); -(3,3,3trifluoropropyl)pyrazole (2-D intermediate) 1-15° ΧΧΎΧ Ν^γ F 2-(difluoromethyl)- 8-methox¡-3-(4-(2,2,2trifluoroethoxy)phenyl)-4H-pyrido[1,2a]pyrimid¡n-4-one 3-bromo-2-(difluoromethyl)-8methoxy-pyrido[1,2-a]p¡ rim id in4-one (Intermediate 1-C);) 1-16 rt O o / 2-(difluoromethyl)8-methoxy-3-(1(4,4,4trifluorobutyl)-1Hpyrazol-4-yl)-4Hpyrido[1,2a]pyrimidin-4-one 3-bromo-2-(difluoromethyl)-8methoxy-pyrido[1,2-a]pyrimidin4-one (Intermediate 1-C); 4(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1 -(4,4,4trifl uorobutyl)-1 H-pyrazole (Intermediate 2-E). 131 RC7QCn / 77n7 / 3 / YILI 1-17 0 / =\ 3-(1-(4fluoropropyl)-1 Ηpyrazol-4-yl)-8methoxy-2(trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one [1-(4-fluorophenyl)-1hpyrazol-4-yl]boronic acid (CombiBlocks Inc.) 1-18 F. Ο ρΛ / =( 0ΧανΧ< IFF 3-(1-(3fluoropropyl)-1Hpyrazol-4-yl)-8methox¡-2(trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one pinacolic ester of 1(3-fluorophenyl)-1 h-pyrazol-4boronic acid (Combiphos Catalysts.) 1-19 F ¿WF \= / F ο ir Π II ΖΝ Ι^Ν 'ΤΤ^' 1α Λ / 0 — Ν χ I f F 8-methoxy-2(trifluoromethyl)-3(1-(3(trifluoromethyl)phenyl )-1 H-pyrazol-4-yl)4H-pyrido[1,2a]pyrimidin-4-one acid (1-[3- (trifl uoromethy I )phen ¡I]-1 hpyrazol-4-yl)boronic (CombiBlocks Inc.) 1-20 Μ ο— 3-(2-fluoro-4(2,2,2trifluoroethoxy)phenyl); -8-Methoxy-2(trifluoromethyl)4H-pyrido[1,2a]pyr¡mid¡n-4-one 2-(2-fluoro-4-(2,2,2trifluoroethoxy)phenyl)-4,4,5,5tetramethyl-1,3,2dioxaborolane (Intermediate 2-F) 1-21 0 riN, FS-CF, 0F acid 4-oxo-3-(1(2,2,3,3,3pentafluoropropyl)-1 H-pyrazol-4-yl)- 2-(trifluoromethyl)- 4H-pyrido[1,12].2- 3-yodo-4-oxo-2(trifluoromethyl I )-4H-pyrido[1,2a]pirim¡din-8-carbox¡late methyl (Intermediate 1-D); 1(2,2,3,3,3-pentafluoropropyl)4-(4,4,5,5-tetramethyl-1,3,2- 132 Rczocn / zznz / q / υιλι a]pyrimidin-8carboxylic acid dioxaborolan-2-yl)-1 H-pyrazol (Intermediate 2-G) 1-22 PF Í^NFIFF 8-(dimethylamino)3-(1-(2,2,3,3,3-pentafluoropropyl) -1 H-pyrazol-4-yl)2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 8-(dimethylamino)-3-yodo-2(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one (Intermediate 1-E), Intermediate 2-G 1-23 % pyrimidin-4-one (Intermediate 1 -F), Intermediate 2-G 1-24 1 íXt 5,5tetramethyl-1,3,2dioxaborolan-2-yl)-1 H- pyrazol-1-yl) (Intermediate 2- H) 1-25 JLO^Í ¡r— 1 FF 8-acetyl-3-(4(2,2,2trifluoroethoxy)phen¡l)-2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 8-acetyl-3-iodo-2(trifluoromethy I )-4H-pyrido[1,2a]pyrimidin-4-one (Intermediate 1-G); (4(2,2,2trifluoroethox¡)phen¡l)boronic acid (Combi-Blocks Inc.) 133 Rczocn / zznz / q / υιλι 1-26 NO r^N / 7 FF (4-(8-methoxy-4oxo-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-3-yl)1 H-pyrazol-1yl)acetonitrile 2-(4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1 Hpyrazol-1-¡l)aceton¡trile (Intermediate 2-I) 1-27 “Π “H 4-oxo-3-(1(2,2,3,3,3- pentafluoropropyl) -1 H-pyrazol-4-yl)2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidine-8carbonitrile 3-iodo-4-oxo-2(tnfluoromethyl)-4H-p¡r¡do[1,2a]pyrimidin-8-carbon¡tr¡lo (Intermediate 1-H), Intermediate 2-G 1-28 zy=o 8-(dimethylamino)3-(4-(2,2,2trifluoroethoxy)phenyl)-2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 8-(dimethylamino)-3-iodo-2(trifluoromethy I). )-4H-pyrido[1,2a]pyrimid¡n-4-one (Intermediate 1-E), (4-(2,2,2tr¡fluoroethoxy¡)phen¡l)boron¡ic acid (Combi-Blocks Inc.) 1-29 / IZ 0 z / =° o “Π 8-(methylamino)-3(4-(2, 20).2,2trifluoroethoxy)phenyl)-2-(trifluoromethyl)- 4H-pyrido[1,2a]pyr¡midin-4-one 3-iodo-8-(methylamino)-2(tr¡fluoromethyl)-4H-p¡r¡do[1,2a]pyrim¡din-4-one (Intermediate 1-F), acid (4(2,2,2trifluoroethox¡)phenyl)boronic (Combi-Blocks Inc.) 1-30 -sXxkNJ0 FF 8-(methylsulfanyl)3-(1-(2,2,3,3,3pentafluoropropyl)-1 H-pyrazol-4-yl)2-(trifluoromethyl)-1. 3-iodo-8-(methylthio)-2(tr¡fluoromethyl)-4H-p¡r¡do[1,2a]pyrim¡d¡n-4-one (Intermediate 1-K); Intermediate 2-G 134 Rczocn / zznz / q / υιλι 4H-pyrido[1,2- a]pyr¡midin-4-one 1-31 or / \ / -(4-oxo-3-(4(2,2,2trifluoroethoxy)phenyl); -2-(Trifluoromethyl)4H-pyrido[1,2a]pyrimidin-8yl)acetamide N-(3-iodo-4-oxo-2(trifluoromethy I )-4H-pyrido[1,2a]p¡r¡r¡din-8-yl)acetamide (Intermediate 1-L), (4(2,2,2trifluoroethoxy)phen¡l)boronic acid (Combi-Blocks Inc.) 1-32 κ o TI 8-(2-propanyl)-3(4-(2,2,2trifluoroethoxy)phen¡l)-2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 3-iodo-8-isopropyl-2(trifluoromethy I). )-4H-pyrido[1,2a]pyrimidin-4-one (1-M intermediate), acid (4(2,2,1).2trifluoroethoxy)phen¡l)borón¡co (Combi-Blocks Inc.) 1-33 N FxL λ g Λ^· Xa1 D3CO^— N^CFj 8-(methyloxy-d3)-3(1-(2,2,3,3,3pentafluoropropyl)-1H-pyrazol-4-yl)2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 3-bromo-8-(methoxy-d3)-2(trifluoromethyl)-4H-p¡rdo[1,2a]pyrimidin-4-one (Intermedio 1-N), Intermedio 2-G 1-34 F FF o «n KL· H nV ¿ r jfXYT I 8-methoxy¡-3-(1(2,2,3,3,3pentafluoropropyl)-1 H-pyrazol-4-yl)2-(trifluoromethyl)4H-pyrimido[1,2a]pyrimidin-4-one 3-Bromo-8-methoxy-2(trifluoromethyl)-4Hpyrimido[1,2-a]pyrimidin-4-one (Intermediate 1-0), Intermediate 2-G 135 1-35 Active IFF 8-(methylsulfanyl)3-(4-(2,2,2trifluoroethoxy)phenyl) -2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one Intermediate 1-K, ácido (4(2,2,2trifluoroethoxy)phenyl)boronico (Combi-Blocks Inc.) 1-36 0 4-oxo-3-(4-(2,2,2trifluoroethoxy)phenyl) -2-(trifluoromethyl)4H-pyr¡do[1,2a]pyrimidine-8carboxylato de methylo Intermedio 1-D, ácido (4(2,2,2trifluoroethox¡)phen¡l)boronic (Combi-Blocks Inc.) 1-37 —o zb >> 3-(4- (cyclopropylmethoxy )phenyl)-8-methoxy¡-2(trifluoromethyl)4H-pyr¡mido[1,2a]pyrimidine-4-one Intermediate 1-0, [4-0 (cyclopropylmethoxy)phen¡l]borane odiol (Combi-Blocks Inc.) 1-38 F .—l— F .----' FO rN ___ Η II -NI r F 8-methox¡-3-(1(4,4,4- trifluorobutyl)-1 Hpyrazol-4-yl)-2(trifluoromethyl)4H-pyrim¡do[1,2a]pyrim¡n-4-one Intermediates 1-0, 2-E 1-39 ° íy- II L .N—' 0 nzVf 3-(1-(2,2difluoropropyl)- 1 H-pyrazol-4-yl)-8methox¡-2(trifluoromethyl)- 4H-pyrido[1,2a]pyrmidin-4-one Intermediate 1-A, 1-(2,2difl uoropropyl)-4-(4,4,5,5tetramethyl-1,3,2dioxaborolan-2-Interpyrol-1H-intermediate) 2-J), 136 ficzQcn / zznz / q / υιλι 1-40 i jfy FF (4-(8-methoxy-4oxo-2(trifluoromethyl)4H-pyrimido[1,2a]pyrimidin-3yl)phenoxy)acetonitrile lo Intermediate 1-O, (4(cyanomethoxy)phen¡l)boronic acid (Combi-Blocks Inc.) 1-41 —OXZ )=O o 3-(4-(2,2difluoroethox¡)-2fluorophenyl)-8methox¡-2(trifluoromethyl)4H-pyrido[1,2a]pyr¡midin-4-one Intermediate 1-B, 2005 . 2-(4-(2,2difluoroethoxy)-2-fluorophenyl)4,4,5,5-tetramethyl-1,3,2dioxaborolane (Enamine Ltd) 1-42 V qV? F r 3-(4-(2,2,2trifluoroethox¡)phen¡l)-2-(trlfluoromethyl)- 4H-pyrido[1,2a]pyrimidin-4-one 3-bromo-2(trifluoromethyl )pyrido[1,2a]pyrimidin-4-one (Intermediate 1-P), acid 4(2,2,2trifluoroethoxy)benzeneboron¡ co (Combi-Blocks Inc.) 1-43 0 r^\ / =^ FF 3-(1-phenyl-1Hpyrazol-4-yl)-2(trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one Intermediate 1-P,1 -phenyl-4(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1 H-pyrazole (Combi-Blocks Inc.).). (Combi-Blocks Inc.). 137 RC7QCn / 77n7 / 3 / ΥΙΛΙ 1-45 7-chloro-8-methoxy3-[1-(2,2,3,3,3pentafluoropropyl)-1 H-pyrazol-4-yl]2-(trifluoromethyl)4H-pyrido[1,2a]pyr¡mid¡n-4-one 7-chloro-3-iodo-8-methox¡-2(trifluoromethy I). )-4H-pyrido[1,2a]pyrimidin-4-one (Intermediate 1-1), Intermediate 2-G 1-46 RZ ugly n^y KT 3-(1-(4fluorophenyl)-1Hpyrazol-4-yl)-2(trifluoromethyl)4H-pyrido[1,2a]pyrim¡d¡n-4-one Intermediate 1-P, . [1-(4fluoropheny I )-1 h-pyrazol-4yl]boronic acid (Combi-Blocks Inc.) 1-47 P 0 Π II zn jOClLf o N pF 8-methox¡-3-(1- phenyl-1H-pyrazol-4yl)-2- . (trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one Intermediate 1-A, pinacolic ester of (1-phenyl1 h-pyrazol-4-yl)boron¡ic acid (Combi-Blocks Inc.) 1-48 oZ 0 z ugly ok 3-(3-fluoro-4(2,2,2- trifluoroethoxy)phenyl); -8-methox¡-2- (trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one Intermediates 1-A,2-F 1-49 / o 0 Z ugly o 8-methoxy-3-(4(trifluoromethoxy)phe nyl)-2- (trifluoromethyl)- . 4H-pyrido[1,2a]pyr¡midin-4-one Intermediate 1-A, 4(trifluoromethoxy)benzenoboronic acid (Oakwood Chemical) <h2 style=";text-align:left;direction:ltr">138 ficzQcn / zznz / q / υιλι<h2 style=";text-align:left;direction:ltr"> 1-50 8-methox¡-3-(4(2,2,2trifluoroethox¡)phenyl) -2-(trifluoromethyl)4H-pyrim¡do[1,2a]pyrim¡d¡n-4-one Intermediate 1-0, Acid 4(2,2,2trifluoroethoxy ca¡5 combinzo)1Combicene η O 0 z AO 3-(4-(2- fluoroethoxy)phenyl)8-(methyloxy-d3)-2(trifluoromethyl)4H-p¡rido[1,2a]pyrimidine-4-one Intermediate 1-N, Acid (4- (2-fluoroethoxy)Incbyl)DOO1-boronic (4- (2-fluoroethoxy)Incbyl)-boronic γο ΑΧα or µ 3-(4-(2,2- difluoroethoxy)phenyl) -8-(methyloxy-d3)-2(trifluoromethyl)- 4H-pyrido[1,2a]p¡r¡d¡n-4-one Intermediate 1-N, 2-(4-lueth(2 )phenyl)-4,4,5,5tetramethyl-1,3,2dioxaborolane (Intermediate 2-C) 1-53 χΧΥ FFF 3-(2-fluoro-4(2,2,2trifluoroethoxy)phenyl) -8-methox¡-2(trifluoroone,pyrymethyl¡n)4 Intermediate 1-O, acid (2fluoro-4-(2,2,2trifluoroethoxy)phenyl)boron¡co (Intermediate 2-L) 1-54 o~ <W a °4 o— 3-(4- (difluorometoxi)fe nil)-8-metoxi-2(trifluorometil)4H-pirido[1,2a]pirimidin-4-ona Intermedio 1-B, ácido 4(difluorometoxi)fenilborón¡co (Combi-Blocks Inc.) 139 Rczocn / zznz / q / υιλι 1-55 8 πν D3CO NN 7C FF 3-(4-(2-fluoroethoxy)phenyl)8-(methyloxy-d3)-2(trifluoromethyl)4H-pyrimido[1,2a]pyrimdn-4-one 3-Bromo-8-(methoxy-d3)-2(trifluoromethyl)-4H-pyrimdo[1,2-a]pyrimdin-4one (Intermediate 1-R), 4-(2-fluoroethoxy)phenylboronic acid (Combi-Blocks Inc.) 1-56 XaX^ H r 1 7-(4-(2-fluoroethoxy)phenyl)8-(trifluoromethyl)2H-pyrimido[1,2a]pyrimidin- 2,6(1H)-dione Intermediate 1-B, acid 4-(2fluoroethoxy)phenylboronic acid (Combi-Blocks Inc.) 1-57 a Or°^FFF 3-(4-(2-fluoroethoxy)phenyl)8-methoxy-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one Intermediate 1-B, 4-(2fluoroethoxy)phenylboronic acid (Combi-Blocks Inc.) 1-58 2-(fluoromethyl)-8methoxy¡-3-(4(2,2,2trifluoroethoxy)phenyl)-4H-pyrido[1,2- a]pyrimidin-4-one 3-bromo-2-(fluoromethyl)-8methoxy-4H-pyrdo[1,2a]pyrimidin-4-one (Intermediate 1-S), 4(2,2,2trifluoroethoxy)benzeneboron¡ acid co (Combi-Blocks Inc.) 1-59 ϋ,αοχν<''Ί'<''η< F 8-(methyloxy-d3)-3(4-(2,2,2- trifluoroethoxy)phen¡l) -2-(trifluoromethyl)4H-pyrimido[1,2a]pyrimidine mediated-4-one R 4(2,2,2trifluoroethoxy)benzeneboron¡ co (Combi-Blocks Inc.). 140 ficzQcn / zznz / q / υιλι 1-60 2-ethyl-8-methoxy-3- (6-(2,2,2-trifluoroethox¡)-3pyridin¡l)-4Hpyrido[1,2a]pyrim¡d¡n-4-one 3-bromo-2-ethyl-8-methoxy-4Hpyrido[1,2-a]p¡rimidin-4-one (Intermediate 1-T), acid [6(2,2,2-trifluoroethoxy)pyridin-3yl]boronic (Combi-Blocks Inc.) 1-61 F AA / N^ F xXC 8-(methyloxy-d3)-2(trifluoromethyl)-3(1-(3,3,3trifluoropropyl)1 H-pyrazol-4-yl)4H-pyrido[1,2a]pyrim¡d¡n-4-one Intermediates 1-N, 2-D 1-62 / 0 z you <| A 4(2,2,2trifluoroethoxy)benceneboronic (Combi-Blocks Inc.) 1-63 o OO ü z tC 8-(methyloxy-d3)-3(1-(4,4,4-tr¡fluorobutyl)-1Hpyrazol-4-yl)-2(trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one Intermediates 1-N, 2-E 1-64 F 8-(methyloxy-d3)-3(6-(2,2,2trifluoroethoxy)-3pyridinyl)-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidine-4-one Intermediate 1-N, [6(2,2,2-trifluoroethoxy)pyridin-3yl]boronic acid (Combi-Blocks Inc.) 141 RC7QCn / 77n7 / q / ΥΙΛΙ 1-65 O ω α oqz feo TV, i 3-(4- (cyclopropylmethoxy )phenyl)-8-(methylox¡d3)-2- (trifluoromethyl)4H-pyrido[1,2a]pyr¡mid¡n-4-one Intermediate 1-N, [4-methoxy¡ranop) (Combi-Blocks Inc.) 1-66 FFFF 8- (difluoromethoxy)- 3-(4-(2,2,2trifluoroethoxy)phenyl) -2-(trifluoromethyl)- 4H-pyrido[1,2a]pyrmid¡n-4-one 3-bromo-8-(difluoromethox¡)2-(trifluoromethyl)-4HPyride[1,2-a]pyrimidine-4-one (Intermediate 1-V), acid 4(2,2,2trifluoroethoxy)benzeneboron¡ co (Combi-Blocks Inc.) 1-methyl phe-67 / 3-(4-(2,2,2trifluoroethoxy)phenyl) -4H-pyrido[1,2- a]pyrim¡d¡n-4-one 3-bromo-8-methoxy-2-methyl4H-pyrido[1,2-a]pyrim¡d¡n-4one (Intermediate 1-ithoron 1-4-Wtribenefobo,2) (Combi-Blocks Inc.) 1-68 EF / F .—\ F 0 fTN' F Π / / ZN jCXjlf Ϊ NFF 8-methoxy-3-(1- (2,2,3,3,3pentafluoropropyl) -1 H-pyrazol-4-yl)- 2-(trifluoromethyl)- 4H-pyrido[1,2a]pyrimidin-4-one Intermediate 1-A, 2-G 1-69 —O z feo 4 ,ί Z 1 -π 8-methoxy-2- (trifluoromethyl)-3- (1-(3,3,3trifluoropropyl)- 1 H-pyrazol-4-yl)4H-pyrido[1,2a]pyrimidin-4-one Intermediate 1-A, 2-D. 142 1-70 -N.___.0.___-A to XjT 8-methox¡-3-(6(2,2,2trifluoroethox¡)-3pyridinyl)-2(trifluoromethyl)4H-pyrim¡do[1,2a]pyrim¡d¡n-4-one Intermediates 1-O, acid [6(2,2,2-trifluoroethoxy¡)p¡r¡d¡n-3yl]boronic (Combi-Blocks Inc.) 1-71 O / =\ oXANJy IFF 8-methoxy-2(trifluoromethyl)-3(1-(4- (trifluoromethyl)phenyl )-1 H-pyrazol-4-yl)4H-pyrido[1,2a]pyr¡mid¡n-4-one Intermediate 1-A), pinacolic ester of 1-(4trifluoromethylphen¡l)-1h-p¡razol4-boronic acid (CombiPhos) 1-72 y. or X / y. w Λ 8-methoxy-3-(4(trifluoromethoxy)phe nil)-2- (trifluoromethyl)4H-pyrimido[1,2a]pyrim¡d¡n-4-one Intermediate 1-O, 4(trifluoromethoxy)benzenoboronic acid (Oakwood Chemicals) 1-73 lÓ^ 3-(3-fluoro-4(2,2,2trifluoroethoxy)phen¡l)-8-methox¡-2(trifluoromethyl)4H-pyrimido[1,2a]pyrimid¡n-4-one Intermediate 1-0, 3fluoro-4-(2,2,2trifluoroethoxy)benzeneboron¡ co acid (Combi-Blocks Inc.).<h2 style=";text-align:left;direction:ltr">) 1-74 F / -O rr\ F xA” IFF 8-metox¡-3-(1(2,2,2- trifluoroetil)-1Hpirazol-4-il)-2(trifluorometil)4H-pirido[1,2a]pir¡mid¡n-4-ona Intermedio 1-A, 4-(4,4,5,5tetrametil-1,3,2dioxaborolan-2-il)-1 -(2,2,2trifluoroeti I )-1 H-pirazol (Intermedio 2-M).<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> 143<h2 style=";text-align:left;direction:ltr"> <h2 style=";text-align:left;direction:ltr"> Rczocn / zznz / q / yi<h2 style=";text-align:left;direction:ltr"> 1-75 F / —VF y---' F 0 II II -N jOTlf ° N ΎΓ 8-methox¡-3-(1- (4,4,4- trifluorobutyl)-1 Hpyrazol-4-yl)-2(trifluoromethyl)- 4H-pyrido[1,2- a]pyr¡midin¡n-4-one Intermediates 1-A, . 2-E 1-76 IFF 8-methox¡-3-(1- propyl-1 H-pyrazol- 4-¡l)-2(trifluoromethyl)- 4H-pyrido[1,2a]pyrim¡n-4-one Intermediate 1-A,1 -propyl-4(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)-1 H-pyrazole (Ark Pharm) 1-77 2-ethyl-8-methox¡-3(4-(2,2,2trifluoroethoxy)phenyl)-4H-pyrido[1,2a]pyrimidin-4-one 3-bromo-2-ethyl-8-methoxy-4Hpyrido[1,2-a]p¡rimidin-4-one (Intermediate 1-T); acid 4(2,2,2- trifluoroethoxy)benzenoboron¡ co (Combi-Blocks Inc.) 1-78 fe 8-methyl-3-(4(2,2,2trifluoroethoxy)phenyl)-2-(trifluoromethyl)4H-pyrido[1,2a]pyrim¡n-4-one 3-bromo-8-methyl-2(tr¡fluoromethyl)-4H-p¡rido[1,2a]pyrimidin-4-one (2-V intermediate); acid 4-(2,2,2trifluoroethoxy)benzenoboron¡ co (Combi-Blocks Inc.) 1-79 CT—^N^CF3 8-methoxy-3-(4propylphenyl)-2(trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one Intermediate 1-A, 4propylphenylboronic acid 144 1-80 0 2,8-dimethox¡-3-(4(2,2,2- trifluoroethoxy)phen¡l)-4H-pyrido[1,2- a]pyr¡midin-4-one 3-iodo-2,8-di methox¡-4 Hpyrido[1,2-a]pyrimidin-4-one (Intermediate 2-W), acid 4(2,2,2trifluoroethoxy)benzeneboron¡ co (Combi-Blocks Inc.); K3PO4 and toluene replacing CS2CO3 and dioxane 1-81 . ^Γ 2-ethoxy-8-methoxy- 3-(4-(2,2,2trifluoroethoxy)phenyl)-4H-pyrido[1,2- a]pyrim¡d¡n-4-one 2-ethoxy-3-iodo-8-methoxy-4Hpyrido[1,2-a]pyrimidin-4-one (Intermediate 2-X), acid 4(2,2,2trifluoroethoxy)benzeneboron¡ co (Combi-Blocks Inc.); K3PO4 and toluene replacing Cs2CO3 and dioxane 1-82 0 r^NS^ II C NZ CF' ^N'^^N'^'CF, H 3 A / -(4-oxo-3-(1(2,2,3,3,3pentafluoropropyl) -1 H-pyrazol-4-yl)2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-8yl)acetamide Intermediates 1 -L, 2-G 1-85 F p 2-(difluoromethyl)4-oxo-3-(1- (2,2,3,3,3- pentafluoropropyl) -1 H-pyrazol-4-yl)4H-pyrido[1,2a]pyrimidin-8carbonitrile 2-(Difluoromethyl)-3-iodo-4oxo-4H-pyrido[1,2a]pyr¡midin-8-carbonitrile (Intermediate 1-J), Intermediate 2-G 145 FtczQcn / zznz / q / υιλι 1-86 F 2-(fluoromethyl)-4oxo-3-(1-(2,2,3,3,3pentafluoropropyl)-1 H-pyrazol-4-yl)4H-pyrido[1,2a]pyrimidin-8-carbonitrilo 2-(Fluoromethyl)-3-yodo-4oxo-4H-pyrido[1,2a]pyrimidin-8-carbonitrilo (Intermediate 2-K), Intermediate 2-G 1-87 i 8-Cyclopropyl-3-(1 (2,2,3,3,3pentafluoropropyl)-1 H-pyrazol-4-yl)2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 8-Cyclopropyl-3-yodo-2(trifluoromethyl I )-4H-pyrido[1,2a]pyrimidin-4-one (Intermediate 3-D), Intermediate 2-G 1-88 z 5=0 i 8-(1 -azetidin¡l)-3(1-(2,2,3,3,3pentafluoropropyl) -1 H-pyrazol-4-yl)2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 8-(azetidin-1-yl)-3-yodo-2(trifluoromethyl I )-4H-pyrido[1,2a]pyrimidin-4-one (Intermediate 3-E), Intermediate 2-G METHOD 2 EXAMPLE 2-1: 8-ETHYL-3-(4-(2,2,2-TRIFLUOROETOXI)PHENYL)-2-(TRIFLUOROMETHYL)-4HPIRIDOÍ1 .2-A1PYRIMIDIN4-ONA ΐί CoCI2, Mg. C2H5L éter dietilicoPaso1 Intermediate 3C .Cf Step 3 146 FOLLOW^JLETILJhíTRIHJJORO^ Cobalt(II) chloride (0.400 g, 3.07 mmol) and freshly prepared Grignard solution - prepared from magnesium turnings (0.67 g, 27 mmol) and iodoethane (0.56 ml, 6.8 mmol) in anhydrous diethyl ether (10 mL) - were added to a solution of 8-bromo-2(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (Intermediate 3-C, 2.0 g, 6.83 mmol) in benzene (15.0 mL) at rt under nitrogen. The reaction mixture was heated to 75 °C for 2 h. The reaction mixture was quenched with aqueous HCl solution (1.5 N, 10 mL). After 10 minutes, the pH of the reaction mixture was adjusted to pH 8 by the addition of NaHCO3 aq. The reaction mixture was extracted with ethyl acetate (2 x 25 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (eluent: 0-40% EtOAc / hexane) to afford 8-ethyl-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.4 g, 24% yield) as a pale yellow solid. LC / MS (ESI+) m / z = 243.1 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.96 (d, J=7.3 Hz, 1H), 7.74 - 7.67 (m, 1H), 7.45 (dd, J=7.2, 2.0 Hz, 1H), 6.76 (s, 1H), 2.83 (c, J=7.5 Hz, 2H), 1.27 (c, J=7.5 Hz, 3H). STEP 2: 8-ETHYL-3-IODO-2-(TRIFLUOROMETHYL)-4H-PYRIDO[1,2-A1PYRIMIDIN-4ONE. NIS (0.84 g, 3.72 mmol, 3.0 eq.) was added to a solution of 8-ethyl-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.3 g, 1.239 mmol) in acetonitrile (6.0 mL). The reaction mixture was heated to 80 °C for 48 h and then concentrated under reduced pressure. The crude residue was purified by silica gel chromatography (eluent: 0-20% ethyl acetate / hexane) to afford compound 8-ethyl-3-iodo-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one (0.4 g, 88% yield) as a yellow solid. LC / MS (ESI+) m / z = 369.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.95 (d, J=7.20 Hz, 1H), 7.73 (s, 1H), 7.50 (dd, J=2.00, 7.40 Hz, 1H), 2.82 (c, J=7.20 Hz, 2H), 1.27 (t, J=7.60 Hz, 3H). STEP 3: 8-ETHYL-3-(4-(2,2,2-TRIFLUOROETHOXY)PHENYL)-2-(TRIFLUOROMETHYL)-4HPIRIDOri,2-A1PYRIMIDIN4-ONE· 8-Ethyl-3-iodo-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one (0.45 g, 1.2 mmol), 1,4-dixoane (5.0 mL), (4-(2,2,2-trifluoroethoxy)phenyl)boronic acid (0.325 g, 1.46 mmol, Combi-Blocks Inc.) and aqueous sodium carbonate solution (1.0 M, 2.5 mL, 2.445 mmol) were placed in a resealable vial at room temperature under a nitrogen atmosphere. The reaction mixture was purged with nitrogen for 15 min, after which Pd(PPh3)4 (0.140 g, 0.122 mmol, Hindustan Platinum) was added. The reaction mixture was stirred and heated to 95 °C for 16 h. The reaction mixture was concentrated under reduced pressure and the crude residue was purified by silica gel chromatography (eluent: 0-5% methanol in dichloromethane) to give 8-ethyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H 147 pyrido[1,2-a]pyrimidín-4-one (0.17 g, 32% yield) as a pale yellow solid. LC / MS (ESI+) m / z = 417.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.93 (d, J=7.3 Hz, 1H), 7.72 (s, 1H), 7.44 (dd, J=7.3, 2.0 Hz, 1H), 7.28 (d, J=8.5 Hz, 2H), 7.16 - 7.08 (m, 2H), 4.84 (c, J=8.8 Hz, 2H), 2.84 (c, J=7.5 Hz, 2H), 1.29 (t, J=7.5 Hz, 3H). Examples 2-2 through 2-9 listed in Table 5 were prepared following the procedure described in Method 2, Step 3, above as follows. Table 5 N.° of Ex. Chemical Structure Reagent Name 2-2 ΗΟγΜΑοΡ, O acid 4-oxo-3-(4(2,2,2trifluoroethoxy)phenyl)-2(trifluoromethyl)-4HPyride[1,2-a]p¡d¡n8-carboxylic 3-iodo-4-oxo-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidine-8methyl carboxylate (Intermediate 1-D) 2-3 TI 0 z / ° oo CJ 8-fluoro-3-(4-(2,2,2- t rif I uo I rhoethoxy )phene )-2(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine4-one 8-fluoro-3-iodo- 2-(trifluoromethyl)- 4H-pyrido[1,2a]pyrimid¡n-4-one (Intermediate 1-Y) 2-4 8 MeO'^^CFia-8N^' (trifluoromethyl)-3-(1(3,3,3-trifluoropropyl)1H-pyrazol-4-yl)-4Hpyrimido[1,2a]pyrimid¡n-4-one 3-bromo-8methox¡-2(trifluoromethyl)pyri mido[1,2a]mediopyrimidone (ΙΟInter-4 4-(4,4,5,5tetramethyl-1,3,2dioxaborolan-2yl)-1-(3,3,3trifluoropropyl)p¡ra 148 Rczocn / zznz / q / υιλι zol (Intermediate 2-D) 2-5 c OX z 2=0 “Π \ C» VZO < o O 8-(methyl-d3)-3-(4- (2,2,2- t rif 1 uo rotoxy )fe ni 1 )-2(trifluoromethyl)-4Hpyridone[pyrimidin4-a 3-iodine-8-(methyld3)-2(trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one (Intermediate 1-Z) 2-6 ohz 2=0 / Π O Ή J1 8-chloro-3-(1- (2,2,3,3,3luoro) 1H-pyrazol-4-yl)-2- (trifluoromethyl)-4Hpir¡do[1,2-a]pyrimid¡n4-one 8-chloro-3-iodo-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidine-4-one (Intermedium 2,3-T,3,3-f -4-(4,4,5,5tetramethyl-1,3,2dioxaborolan-2yl)-1 H-pyrazole (Intermediate 2-G) 2-7 ocz 2=° oo 8-chloro-3-(4-(2,2,2- t rif I uo rotoxy )fe or I )-2(trifluoromethyl)-4Hpyrido[1,2-a]pinm¡din4-one 8-chloro-3-iodo-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidine-4-one (Intermediate 2-T) 2-8 hz / =° or < O 8-ethenyl-3-(4-(2,2,2trifluoroethoxy)phenyl)-2(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine4-one 3-iodo-2(trifluoromethyl)-8vin¡lp¡rido[1,2a]pyrimidine-medium-4-zone z49-one (Inter) or < or TI 4-oxo-3-(4-(2,2,2- trifluoroethoxy)phenyl)-2(tñfluoromethyl)-4Hpi rido[1,2-a]p¡rim¡di n8-carbonitrilo 3-yodo-4-oxo-2(tr¡fluoromet¡l)p¡r¡do[1,2a]pyrimidin-8carbonitrilo (Intermediate 1-H), METHOD 3 EXAMPLE 3-1: 2-ETHYL-8-METOXI-3-Í1 -(2.2.3,3,3-PENTAFLUOROPROPYL)-1 H-PIRAZOL-4IL)-4H-PYRIDOn,2-A1PYRIMIDIN-4-ONA Dioxane, 95 'C Intermediate 1-T Step 1 STEP 1: 2-ETHYL-8-METHOXI-3-(1 -(2,2,3,3,3-PENTAFLUOROPROPYL)-1 H-PIRAZOL-4-IL)-4HPIRIDOM .2-A1PYRIMIDIN^-ONA. In a resealable vial were charged 3-bromo-2-ethyl-8-methoxy-4H-pyrido[1,2-a]pyrimidin-4-one (9.0 g, 31.8 mmol, Intermediate 1-T), (1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)boronic acid (9.3 g, 38 mmol, Intermediate 2-G), potassium phosphate (10 g, 48 mmol) and 1,4-dioxane (70 mL). The reaction mixture was purged with nitrogen for 10 min, after which Pd(dppf)Ch (2.3 g, 3.2 mmol) was added. The reaction mixture was heated to 95 °C for 16 h. The reaction mixture was allowed to cool to room temperature and filtered through a pad of celite. The celite was washed with ethyl acetate (2 x 250 mL) and the filtrate was concentrated under reduced pressure. The crude residue was adsorbed onto a plug of silica gel and purified by silica gel chromatography (eluent: 0-35% ethyl acetate / hexane) to give 2-ethyl-8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1 H -pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one (7.9 g, 19.6 mmol, 62% yield) as a light orange solid. LC / MS (ESI+) m / z = 403.1 [M+H]+.1H NMR (300 MHz, DMSO-d6) δ 8.89 - 8.74 (m, 1H), 8.10 (s, 1H), 7.78 (s, 1H), 7.07 - 6.92 (m, 2H), 5.26 (t, J=15.2 Hz, 2H), 3.99 (s, 3H), 2.71 (c, J=7.5 Hz, 2H), 1.21 (t, J=7.5 Hz, 3H). Example 3-2 listed in Table 6 was prepared following the procedure described in Method 3, Step 1, above as follows. Table 6 150 Ex No.- Chemical structure Name Reagent 3-2 N 0 rsN Ύ-CFj Jj L. N— / XajC d3co NN ] <h 8-(metiloxi-d3)-3-(1(2,2,3,3,3pentafluoropropil)1 H-pirazol-4-il)-2(trifluorometil)-4Hpirimido[1,2a]pirimidin-4-ona 3-Bromo-8-(metoxid3)-2-(trifluorometil)4H-pirimido[1,2a]pirimidin-4-ona (Intermedio 1-R) METHOD 4 EXAMPLE 4-1: 3-(4-(2,2.2-TRIFLUOROETHOXY)PHENYL)-2.8-BIS(TRIFLUOROMETHYL)-4HPIRIDOM,2-A1PYRIMIDIN4-ONE OH Br2, AcOH Step 2 EITHER Step 3 STEP 1: 2,8-BIS(TRIFLUOROMETHYL)-4H-PYRIDOri.2-A1PYRIMIDIN-4-ONA· A solution of 4-(trifluoromethyl)pyridin-2-amine (2.5 g, 15.4 mmol, ArkPharm) and 4,4,4-trifluoroacetoacetic acid ethyl ester (3.4 mL, 23 mmol) in acetic acid (6 mL) was heated to 110 °C for 20 h. The reaction mixture was cooled to rt and neutralized with saturated bicarbonate solution. The reaction mixture was partitioned with EtOAc and the aqueous layer was back-extracted with EtOAc. The combined organic phases were dried over MgSO4, filtered, concentrated, and adsorbed onto a pad of silica gel. The crude residue was purified by silica gel chromatography (eluent: 0-10% (3:1 EtOAc in Ethanol) / heptane) to afford 2,8-bis(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (0.27 g, 0.97 mmol, 6% yield) as a white solid. LC / MS (ESI+) m / z = 283.0 [M+H]+. 151 STEP 2: 3-BROMO-2,8-BIS(TRIFLUOROMETHYL)-4H-PYRIDO-2-A1-PYRIMIDIN-4-ONE A solution of bromine (0.25 mL, 4.8 mmol) in acetic acid (1.382 mL) was added dropwise to a solution of 2,8-bis(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.27 g, 0.97 mmol) in acetic acid (3.5 mL) at rt. After 24 h, the reaction mixture was cooled to 0 °C and quenched by the dropwise addition of saturated thiosulfate solution (5 mL). The reaction mixture was partitioned between EtOAc and brine, and the aqueous layer was back-extracted 3x with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The resulting solid was washed by cleavage with Et20 to afford 3-bromo-2,8-bis(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.35 g, 0.97 mmol, 99% yield) as a white solid. The product was used in the next step without further purification. LC / MS (ESI+) m / z = 361.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 9.17 (d, J=7.5 Hz, 1H), 8.10 (s, 1H), 7.41 (d, J=7.3 Hz, 1H). PASO 3: 3-(4-(2,2,2-TRIFLUOROETOXI)PHENIL)-2,8-BIS(TRIFLUOROMETIL)-4HPIRIDOfl .2-A1PIRIMIDIN-4-ONA. SPhos Palladacyclo (0.012 mL, 0.017 mmol, Strem Chemicals, Inc.), cesium carbonate (0.173 g, 0.532 mmol, Strem Chemicals, Inc.), 3-bromo2,8-bis(trifluoromethyl)-4H-pyrido[1,2-a]pyrimdin-4-one (0.12 g, 0.332 mmol), and (4-(2,2,2-trifluoroethoxy)phenyl)boronic acid (0.110 g, 0.499 mmol, Combi-Blocks Inc.) were charged into a resealable vial. The vial was evacuated and filled with nitrogen. This procedure was repeated 3 times, after which 1,4-dioxane (1.6 mL) was added. The reaction mixture was heated to 40 °C. After 2 h, the reaction mixture was partitioned between water and EtOAc. The organic phase was separated, washed with brine, dried over magnesium sulfate, filtered, and adsorbed onto a pad of silica gel. The crude product was purified by silica gel chromatography (eluent: 0-10% (3:1 EtOAc in Ethanol) / heptane) to afford 3-(4-(2,2,2-trifluoroethoxy)phenyl)-2,8-bis(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one (45 mg, 0.1 mmol, 30% yield) is obtained as an off-white solid. LC / MS (ESI+) m / z = 457.0 [M+H]+.1H NMR (DMSO-d6, 500MHz) δ 9.08 (d, J=7.5 Hz, 1H), 8.36 (s, 1H), 7.67 (dd, J=7.5, 1.9 Hz, 1H), 7.28-7.31 (m, J=8.7 Hz, 2H), 7.14-7.17 (m, 2H), 4.84 (c, J=8.8 Hz, 2H). Examples 4-2 through 4-3 listed in Table 7 were prepared following the procedure described in Method 4, Step 1, above as follows. TABLE 7 Ex. No. Chemical Structure Name Reagent 152 4-2 rW' 8-cyclopropyl-3-(4(2,2,2trifluoroethoxy)phenyl)-2-(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4-one 3-bromo-8cyclopropyl-2(trifluoromethyl)4H-pyrido[1,2a]pyrimidin-4one (Intermediate 1- X) 4-3 2 Φ hooo 8-methoxy¡-3-(2-methyl-4-(2,2,2trifluoroethoxy)phen¡l)-2-(trifluoromethyl)- 4H-pyrido[1,2a]pyrimidin-4-one Intermediate 1A, (2methyl-4-(2,2,2trifluoroethoxy)phenyl)boronic acid (Intermediate 2- S) METHOD 5 EXAMPLE 5-1: 3-(2-FLUORO-4-(2,2,2-TRIFLUOROETHOXI)PHENYL)-2-(TRIFLUOROMETHYL)20 4H-PYRIDOÍ1,2-A1PYRIMIDIN-4-ONE Intermediate 1-P Step 1 PASO 1: 3-(2-FLUORO-4-(2,2.2-TRIFLUOROETHOXI)PHENYL)-2-(TRIFLUOROMETHYLMHPIRIDOM ,2-A1PYRIMIDIN-4-ONA). 2-(2-Fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (218 mg, 0.68 mmol, Intermediate 2-F), Sphos Palladacyclo G3 (27 mg, 0.034 mmol, Strem), 3-bromo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (100 mg, 0.34 mmol, Intermediate 1-P), and sodium carbonate (72 mg, 0.68 mmol) were placed in a resealable vial. The vial was evacuated and filled with nitrogen. This procedure was repeated 3 times, after which 1,4-dioxane (800 pL) and water (200 pL) were added. The reaction mixture was heated to 85°C. After 2 h, the reaction mixture was partitioned between water and EtOAc, and filtered through a pad of silica gel. The filtrate was washed sequentially with 11 N HC1 (50 mL), sodium bicarbonate aq. 153 sat. (50 mL) and brine (50 mL). The organic phase was dried over magnesium sulfate, filtered, and concentrated. The crude residue was purified by SFC ((IC, 150 x 21 mm, 5 pm), 10% (20 mM NH3 in MeOH) / CO2, 80 g / min, 100 bar) to give 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one (32 mg, 0.08 mmol, 23% yield) was obtained as a white solid. LC / MS (ESI+) m / z = 407.6 [M+H]+.1H NMR (400 MHz, CD2CI2) δ 4.45 (c, J=8.02 Ηζ, 2H) 6.82 (dd, J=10.76, 2.54 Hz, 1H) 6.86 (dd, J=8.41,2.54 Hz, 1H) 7.27 (t, J=8.41 Hz, 1H)7.31 -7.38(m, 1H)7.83 (d, J=8.80 Hz, 1H) 7.89 - 8.03 (m, 1H)9.07 (d, J=7.24 Hz, 1H). Examples 5-2 through 5-4 listed in Table 8 were prepared following the procedure described in Method 5, Step 1, above as follows. TABLE 8 N.° de Ej. Chemical Structure Reactive Name 5-2 π LL □ ) 0 3-(3-cloro-4(2,2,2trifluoroethoxy)phenyl) -2-(trifluoromethyl)- 4H-pirido[1,2a]pirimidin-4-ona 2-(3-cloro-4-(2,2,2trifluoroethoxy)phenyl)4,4,5,5-tetramethyl1,3,2dioxaborolano (Intermediate 2-N) 5-3 3-(1 -cyclopropyl- 1 H-pyrazol-4-yl)-2(trifluoromethyl)- 4H-pirido[1,2a]pirimidin-4-ona 1 -cyclopropyl-4(4,4,5,5-tetramethyl1,3,2dioxaborolan-2-yl)- 1 h (Synthonix Corp.) 5-4 R z 2=0 0 Y—, m Γ \ z η φ 3-(1-propyl-1Hpyrazol-4-yl)-2(trifluoromethyl)- 4H-pyrido[1,2a]pyrimidin-4-ona 1 -propyl-4-(4,4,5,5tetramethyl-1,3,2dioxaborolan-2-yl)1H-pyrazol (ArkPharm) 154 METHOD 6 EXAMPLE 6-1: 8-AMINO-3-(1-(2.2,3,3,3-PENTAFLUOROPROPYL)-1H-PYRAZOL-4-YL)-2(TRIFLUOROMETHIL)-4H-PYRIDOÍ1,2-A1PYRIMIDIN-4-ONA Example 1-82 Step 1 STEP 1: 8-AMINO-3-(1-(2,2,3,3,3-PENTAFLUOROPROPYL)-1H-PYRAZOL-4-YL)-2(TRIFLUOROMETHYL)-4H-PYRIDOn .2-A1PYRIMIDIN-4-ONA. A 10% aqueous sodium hydroxide solution (0.8 mL, 1.92 mmol) was added to a solution of A / -(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2(t-fluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)acetamide (0.3 g, 0.64 mmol, Example 1-82) in methanol (10.0 mL) at rt. After 15 min, the reaction mixture was concentrated under reduced pressure, the residue was dissolved in 5% methanol solution in DCM (50 mL) and washed with water (2 x 20 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by silica gel chromatography (eluent: 0-65% EtOAc / hexane) to afford 8-amino-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.165 g, 0.39 mmol, 60% yield) as a pale yellow solid. LC / MS (ESI+) m / z = 428.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ 8.72 (dd, J=7.8, 1.5 Hz, 1H), 7.88 (s, 1H), 7.57 (s, 1H), 7.39 (s, 2H), 6.88 (dt, J=7.9, 2.0 Hz, 1H), 6.53 (t, J=2.0 Hz, 1H), 5.23 (t, J=15.0 Hz, 2H). Example 6-2 listed in Table 9 was prepared following the procedure described in Method 6, Step 1, above as follows. TABLE 9 No. of Ex. Chemical Structure Name Reagent 6-2 X h Z 2=0 oo 8-amino-3-(4- (2,2,2- trifluoroethoxy)phenyl)- 2-(trifluoromethyl)4H-pyrido[1,2a]pyrimid¡n-4-one Example 1-31 155 METHOD 7 EXAMPLE 7-1: 3-(2-FLUORO-6-(2,2,2-TRIFLUOROETHOXI)-3-PYRIDINYL)-8-METHOXY-2(TRIFLUOROMETHYL)-4H-PYRIDO1,2-A1PYRIMIDIN-4-ONE Intermediate Intermediate 1 H Step 1 STEP 1: 3-(2-FLUORO-6-(2,2,2-TRIFLUOROETHOXY)-3-PYRIDINIL)-8-METHOXY-2(TRIFLUOROMETHYL)-4H-PYRIDOÍ1.2-A1PYRIMIDIN-4-ONE, A solution of isopropylmagnesium chloride (2M in THF, 0.5 ml, 1.1 mmol, Acros Organics, Geel, Belgium) was added dropwise to a solution of 3-iodo-8-methoxy-2-(trifluoromethyl)4H-pyrido[1,2-a]pyrimidin-4-one (Intermediate 1-B, 0.367 g, 0.992 mmol) in THF (1 mL) at 0 °C under a nitrogen atmosphere. The reaction mixture was stirred for 15 min at 0 °C, after which ZnCl2 (0.5M in THF, 2.2 ml, 1.1 mmol) was added dropwise. The reaction mixture was allowed to warm to rt over 1 h and was subsequently added to a 20 min standing solution of [(SIPr)PdCl2]2 (47 mg, 0.04 mmol, Umicore Ag & Co.Kg., Rodenbacher, Germany) and 3-bromo-2-fluoro-6-(2,2,2-tnfluoroethoxy)pyridine (Intermediate 2-O, 0.23 g, 0.83 mmol) in THF (1 mL). The reaction mixture was then heated to 70 °C for 12 h. The reaction was cooled to rt, filtered through a pad of celite, concentrated, and adsorbed onto a pad of silica gel.The crude residue was purified by silica gel chromatography (eluent: 0-40% (EtOAc / EtOH 3:1) / heptane) to give 3-(2-fluoro-6-(2,2,2-trifluoroethoxy)-3-pyridine)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.17 g, 0.38 mmol, 46% yield) as a light yellow solid. MS (ESI+) m / z = 438.1 [M+H]+.19F NMR (376 MHz, CDCI3) δ -73.81 (s, 1 F)-69.99 (da, J=1.74 Hz, 1 F)-65.15 (d, J=2.60 Hz, 1 F).1H NMR (400 MHz, CDCI3) δ 3.90-4.13 (m, 3H) 4.60 -4.83 (m, 2H) 6.72 -6.89 (m, 1H) 6.91 7.04 (m, 1H) 7.04-7.17 (m, 1H) 7.57-7.73 (m, 1H) 8.88-9.06 (m, 1H). Examples 7-2 through 7-6 listed in Table 10 were prepared following the procedure described in Method 7, Step 1, above as follows. TABLE 10 Ex. No. Chemical Structure Name Reagent 156 RC7QCn / 77n7 / 3 / YILI 7-2 ¢7 u> o \\ 'Λ / / IX. 'i—YO Ü 3-(5-(2,2,2- trifluoroethoxy)-2pyridinyl)-2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyr¡midin-4-one Intermediate 1P, 2-bromo-5(2,2,2trifluoroethoxy)p ridine (2,2,2-trifluoroethoxy)p intermediate 3-7 / =° z=Z o <n ω 3-(5-fluoro-6- (2,2,2- trifluoroetoxi)-3piridinil)-8-metoxi2-(trifluorometil)- 4H-pirido[1,2- a]pirimidin-4-ona 5-bromo-3fluoro-2-(2,2,2trifluoroetoxi)p¡ ridina (Intermedio 2- Q) 7-4 F |F Λ .N___O.___<Kr i rr F F 8-metoxi-3-(6(2,2,2trifluoroetox¡)-3piridinil)-2- (trifluorometil)4H-pirido[1,2a]pirimid¡n-4-ona 5-bromo-2(2,2,2trifluoroetoxi)p¡ ridina (Intermedio 2- R) 7-5 3 φ O z 2=0 o ω 8-metox¡-2- (trifluorometil)-3(4-(3,3,3- trifluoropropil)fenil )-4H-pirido[1,2a]pirimid¡n-4-ona 1-bromo-4(3,3,3trifluoropropil)b enceno (Oakwood Products) 7-6 X X jT^ MeO^—^N^^CF- 8-metoxi-3-(6propil-3-piridinil)2-(trifluorometil)4H-pirido[1,2a]pirimidin-4-ona 3-bromo-6-(npropil)piridina (CombiPhos Catalysts, Inc.) 157 METHOD 8 EXAMPLE 8-1: 3-(4-(CYCLOPROPILMETHOXY)-2-FLUOROPHENYL)-8-METHOXY-2(TRIFLUOROMETHYL)-4H-PYRIDOÍ1.2-A1PYRIMIDIN-4-ONE Step 2 STEP 1: 3-(2-FLUORO-4-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4HPIRIDOM .2-A1PYRIMIDIN-4-ONE. The title compound was prepared using the procedure described in Method 1, Step 1 with the following modifications: Step 1 performed with 2-fluoro-4-hydroxybenzeneboronic acid pinacolic ester (Combi-Blocks Inc.). MS (ESI+) m / z = 355.0 [M+H]+. STEP 2: 3-(4-(CYCLOPROPILMETHOXY)-2-FLUOROPHENYL)-8-METHOXY-2(TRIFLUOROMETHYL)-4H-PYRIDOf1.2-A1PYRIMIDIN4-ONE· 3-(2-Fluoro-4-hydroxyphenyl)-8-methoxy-2-(trifluoromethyl)4H-pyrido[1,2-a]pyrimidine-4-one (309 mg, 0.87 mmol) and cesium carbonate (1.3 g, 3.9 mmol) were placed in a resealable vial. The vial was evacuated and filled with nitrogen. This procedure was repeated 3 times, after which DMF (4 mL) and (bromomethyl)cyclopropane (0.127 mL, 1.308 mmol) were added. The reaction mixture was heated to 80 °C for 12 h. The reaction mixture was cooled to rt and filtered through a plug of Celite. The filtrate was extracted with EtOAc (100 mL), and the organic phase was washed sequentially with water (100 mL) and 1 M LiCl (100 mL). The organic phase was dried with anhydrous magnesium sulfate, filtered through Celite, and concentrated under reduced pressure.The crude residue was adsorbed onto a plug of silica gel and purified by silica gel chromatography (eluent: 0-40% EtOAc / heptane) to give 3-(4-(cyclopropylmethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (184 mg, 0.45 mmol, 52% yield) as a light yellow solid. MS (ESI+) m / z = 409.0 [M+H]+.1H NMR (400 MHz, CD2CI2) δ 0.33 - 0.41 (m, 2H) 0.61 - 0.71 (m, 2H) 1.23 - 1.39 (m, 1H) 3.85 (d, J=7.05 Hz, 2H) 4.02 (s, 3H) 6.72 (dd, J=11.61,2.28 Hz, 1H) 6.78 (dd, J=8.50, 2.28 Hz, 1H) 6.95 (dd, J=7.88, 2.70 Hz, 1H) 7.06 (d, J=2.49 Hz, 1H) 7.16 (t, J=8.50Hz, 1H) 8.92 (d, J=7.88 Hz, 1H). 158 Examples 8-2 through 8-5 listed in Table 11 were prepared following the procedure described in Method 8, Step 2, above as follows. TABLE 11 No. Ex. Chemical Structure Name Method Changes Reagent 8-2 Φ o X z / =°^ \ / CJ o < o 8-methoxy-3-(4(2,2,2-trifluoroethoxy)-2(trifluoromethyl)phenyl)-2(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one 3-(4-hydroxy-2(trifluoromethyl)phenyl)-8-methoxy-2(trifluoromethyl)-4H-pyrido[1,2a]pyrimidín-4-one (Intermediate 2-Y), 1,1,1-trifluoro-2-iodoethane (Oakwood Products Inc.) 8-3 <P O X Z )=O \—f o o < o 3-(2-cloro-4(2,2,2trifluoroetoxi)fe nil)-8-metox¡-2(trifluorometil)- 4H-pirido[1,2a]pirimidin-4ona 3-(2-cloro-4hidroxifenil)-8metoxi-2(trifluorometil)-4Hpirido[1,2a]pirim¡d¡n-4-ona (Intermedio 2-Z), 1,1,1-trifluoro-2yodoetano (Oakwood Products Inc.) 8-4 z o oz 4 o / 2-(4-(8-metoxi4-oxo-2(trifluorometil)4H-pirido[1,2a]pirimidin-3il)fenoxi)propan onitrilo Paso 2: K2CO3, acetona, ta 3-(4-hidroxifeniI)8-metox¡-2(trifluorometil)-4Hpirido[1,2a]pirim¡din-4-ona (Intermedio 3-A), 2- 159 bromopropanenitrile 8-5 λ .0. -CN S jfY YONN CF3 2-(4-(8-methoxy4-oxo-2(trifluoromethyl)4Hpyrimido[1,2a]pyrimidin-3yl)phenoxy)propan onitrile Step 2: K2CO3, acetone, 70°C 3-(4-hydroxyphenyl)8-methoxy¡-2(trifluoromethyl)-4Hpyrimido[1,2a]pyrimidín-4-one (Intermediate 3-B), 2-bromopropanonitrile METHOD 9 EXAMPLE 9-1: 8-METHOXY-3-(4-(2,2,3,3-TETRAFLUOROPROPOXY)PHENYL)-2(TRIFLUOROMETHYL)-4H-PYRIDOri,2-A1PYRIMIDIN-4-ONE Intermediate 3-A Intermediate 1 A tBuBrettPhos Paladaciclo G3 NaOtBu, Dioxane Step 5 160 STEP 1: 3-(4-HYDROXYPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri.2A1PYRIMIDIN-4-ONE· The title compound was prepared using the procedure described in Method 1, Step with the following modifications: Step 1 performed with 2-fluoro-4-hydroxybenzeneboronic acid pinacolic ester (Combi-Blocks Inc.). MS (EST) m / z = 337.0 [M+H]+. STEP 2: 4-(8-METHOXY-4-OXO-2(TRIFLUOROMETIL)-4H-PYRIDOri,2-A1PYRIMIDIN-3-IL)PHENYL TRIFLUOROMETHANESULFONATE· A reaction mixture of 3-(4-hydroxyphenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one (0.5 g, 1.5 mmol), pyridine (0.25 ml, 3.0 mmol), and dichloromethane (7 ml) was cooled to 0 °C, after which trifluoromethanesulfonic anhydride (0.3 ml, 1.8 mmol) was added. The reaction mixture was allowed to warm to rt and then stirred for another 2 h. The crude material was adsorbed onto silica gel and purified by silica gel chromatography (eluent: 0-30% (EtOAc / EtOH 3:1) / heptane) to give 4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenyl trifluoromethanesulfonate (0.64 g, 1.36 mmol, 91% yield) as a white solid. MS (ESI+) m / z = 469.0 [M+H]+. STEP 3: 8-METHOXI-3-(4-(4,4,5,5-TETRAMETHYL-1,3,2-DIOXABOROLAN-2-IL)PHENYL)2-(TRIFLUOROMETHYL)-4H-PYRIDori,2-A1PYRIMIDIN-4-ONE. Pd(dppf)Cl2 (0.100 g, 0.136 mmol) and 4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenyl trifluoromethanesulfonate (0.64 g, 1.4 mmol) were placed in a vial. The vial was evacuated and filled with nitrogen. This procedure was repeated 3 times, after which 1,4-dioxane (6.80 ml) and triethylamine (0.57 ml, 4.1 mmol) were added. The reaction mixture was heated to 80°C for 6 h. The reaction mixture was cooled to rt, filtered through a pad of celite, adsorbed onto a pad of silica gel, and purified by silica gel chromatography (eluent: 0-30% (EtOAc / EtOH 3:1) / heptane) to give 8-methoxy-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one (0.8 g, 1.8 mmol, 75% purity). The product was used in the next step without further purification. MS (ESI+) m / z = 447.0 [M+H]+. STEP 4: 3-(4-BROMOPHENYL)-8-METHOXY-2-(TRIFLUOROMETHYL)-4H-PYRIDOri,2A1PYRIMIDIN-4-ONE. A reaction mixture of 8-methoxy-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.61 g, 1.36 mmol), copper(II) bromide (0.9 g, 4.1 mmol), water (1 mL), and methanol (6 mL) was heated to 90 °C for 5 h. The reaction mixture was cooled to rt, partitioned between EtOAc and water. The organic phase was washed with water and brine, and adsorbed onto a pad of silica gel. The crude product was purified by silica gel chromatography (eluent: 10-30% EtOAc / EtOH 3:1 in heptane) to give 3-(4-bromophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (0.34 g, 161 0.86 mmol, 90% purity). The product was used in the next step without further purification. MS (ESP) m / z = 398.9 [M+H]+. STEP 5: 8-METHOXY-3-(4-(2,2,3,3-TETRAFLUOROPROPOXY)PHENYL)-2-(TRIFLUOROMETHYL)4H-PYRIDO[1,2-A1PYRIMIDIN-4-ONE. 3-(4-Bromophenyl)-8-methoxy-2-(trifluoromethyl)-4Hpirido[1,2-a]piñomidin-4-one (50 mg, 0.125 mmol), sodium phenylbutoxide (17 mg, 0.175 mmol), and tBuBrettPhos Palladacyclo G3 (6 mg, 7.5 pmol) were placed in a resealable vial. The vial was evacuated and filled with nitrogen. This procedure was repeated three times, after which 1,4-dioxane (835 μl) and 2,2,3,3-tetrafluoro-1...

Claims

1. A compound of Formula I or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer, wherein Rw is H, halogen, -CN, -CO(Cm alkyl), -S(O)n(Cm alkyl), -COOH, -COO(Cm alkyl), -CONH2, -CONH(Cu alkyl), -CO(di(C1-4 alkyl)amino), -NH2, (alkyl hexamino, di(CuJamino, -NH(CO(C14 alkyl)), -N(Cm alkyl)C(=O)F, C1,4 alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl, C2-4 alkenyl, Cm deuteroalkoxy, or 5-membered heteroaryl; wherein the Cm alkyl and C3-4 heterocycloalkyl groups are optionally substituted with 1 to 4 substituents selected independently from halogen, OH, -CN, alkoxy Cm, alkyl C1.4, -NH2, (C1-4 alkyl)amino, di(alkyl hexamino, and -S(O)n(C1-4 alkyl); Ry is H, F, Cl, -OH, -CN, -CO(C1-4 alkyl), -S(O)n(C1-4 alkyl), -COOH, -COO(C1-4 alkyl), -CONH2, -CONH(C1-4 alkyl), -CO(di(C1-4 alkyl)amino), -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl hexamino, -NH(CO(C1-4 alkyl)), -N(C1-4 alkyl)C(=O)F, C1-4 alkyl, C1-4 deuteroalkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 deuteroalkoxy, or 5-membered heteroaryl; wherein the C1-4 alkyl, C3-4 heterocycloalkyl, and C1-4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, alkoxy Ciu, alkyl Cu, -NH2, (alkyl Ciu)amino, di(alkyl hexamino and S(O)n(alkyl Ciu); Rx and Rz are independently H, halogen, -OH, -CN, -CO(C1-4 alkyl), S(O)n(alkyl Ciu), -COOH, -COO(alkyl Cu), -CONH2, -CONH(alkyl C1.4), -CO(di(alkyl Ci4)amino), -NH2, (alkyl Ciu)amino, di(alkyl Ci-4)amino, -NH(CO(alkyl C1-4)), -N(alkyl Ci4)C(=O)F, Ciu alkyl, Cu deuteroalkyl, C3-5 cycloalkyl, C3-4 heterocycloalkyl, C2.4 alkenyl, C1-4 alkoxy, Cm deuteroalkoxy or 5-membered heteroaryl; where the Cu alkyl, C3-4 heterocycloalkyl and C1-4 alkoxy groups are optionally substituted with 1 to 4 substituents selected independently from halogen, -OH, -CN, C1.4 alkoxy, Cu alkyl, -NH2, (alkyl hexamino, di(alkyl hexamino, and -S(O)n(Cm alkyl); R1 is H, Cu alkyl, C« haloalkyl or Cu deuteroalkyl; x is O, NH or N(C1-4 alkyl); ír τα.R2 is A; AR\ '--yo 2-benzofuranyl, where A is independently CH or N, and where AR is not R; and B is a 5-membered heteroaryl containing a heteroatom selected from N, S and O, and optionally one or two additional N atoms, where i) B is bonded through a C atom to the bicyclic core and R3 is bonded through an N atom; or i) B is bonded through an N atom to the bicyclic core and R3 is bonded through a C atom; or iii) B is bonded through a C atom to the bicyclic core and R3 is bonded through a C atom; W 2 and where the A portion; A ¿ 0 '•—y of r2 oe| 2-benzofuranyl is further optionally substituted with one or two independently selected R3 substituents; 303 R3 is CH2CN, C2-6 alkyl, C3-5 cycloalkyl, C1-3 alkoxy, (Ci-6 alkyl)amino, di(C· alkyl,.6)amino, -S(O)n(Ci-β alkyl), -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl), NHCH2(C3-5 cycloalkyl), -S(O)nCH2(C3-5 cycloalkyl), -CH2(C3-5 heterocycloalkyl) or phenyl; where the C2-6 alkyl, C3-5 cycloalkyl, C1.3 alkoxy, (alkyl hexamino, di(C1-6)alkyl)amino, -S(O)n(C1-β alkyl), -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl), -NHCH2(C3-s cycloalkyl) and -S(O)nCH2(C3-5 cycloalkyl) groups are optionally substituted with 1-9 halogen atoms and are optionally substituted with -CN and where the phenyl is optionally substituted with 1-3 substituents selected from halogen, Cm alkyl, Cm haloalkyl, Cm alkoxy and Cm haloalkoxy; R3' is independently halogen, Cm alkyl, Cm haloalkyl, Cm alkoxy or Cm haloalkoxy; R4 is C1-3 alkyl, haloalkyl Cm, Cm alkoxy, Cm haloalkoxy, C3-5 cycloalkyl or C3-5 cyclohaloalkyl; yn is 0, 1 or 2.

2. The compound of information with the Reivindicación 1, or a tautómero de este, or a sal pharmaceutically acceptable of this compound or of that tautómero, where the compound is not 3-[2-(2,2,2-tr¡fluoroethox¡)p¡r¡m¡d¡n-5-¡l]-2-(trifluoromet¡l)-4H,6H,7H,9H-pir¡m¡do[2,1c][1,4]oxazin-4-ona; 7-(azet¡d¡n-1-¡l)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-p¡razol-4-yl]-2-(tr¡fluoromet¡l)-4Hpyrido[1,2-a]p¡rim¡d¡n-4-one; 7-[(d¡metilam¡no)metil]-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-p¡razol-4-¡l]-2(trifluoromet¡l)-4H-p¡r¡do[1,2-a]pyrimidin-4-one; 7-chloro-3-[2-(2,2,2-trifluoroethox¡)p¡r¡midin-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin4-ona; 7-cyclopropyl-3-[2-(2,2,2-trifluoroethoxy)pyrimid¡n-5-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimid¡n-4-ona; 7-fluoro-3-[2-(2,2,2-trifluoroethox¡)p¡r¡m¡din-5-¡l]-2-(trifluoromet¡l)-4H-p¡rido[1,2a]pyrimid¡n-4-ona; 7-methox¡-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-¡l]-2-(tr¡fluoromet¡l)-4Hpirimido[1,2-b]pyridazin-4-one;7-methoxy-3-[2-(2,2,2-trifluoroethoxy)pyrimidín-5-yl]-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazín-4-one; 7-methyl-3-[2-(2,2,2-trifluoroethoxy¡)p¡nm¡din-5-yl]-2-(trifluoromethyl)-4H-p¡razino[1,2a]pyrim¡din-4-one; 304 7-methyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazin-4-one; 8-methoxy¡-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,4-triazol-3-¡l]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidín-4-one; 8-methoxy-3-[3-(2,2,2-trifluoroethoxy¡)phenyl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; or methyl 4-oxo-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-7-carboxylate.; 3. The compound according to Claim 1 or Claim 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 Rz O IA.

4. The compound according to Claim 1 or Claim 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 IB Rw IB.

5. The compound according to Claim 1 or Claim 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 or Rw IC.

6. The compound according to any one of Claims 1, 2, 4 and 5, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein 305 Rw is H, halogen, -CN, -CO(Cm alkyl), -S(O)n(C1-4 alkyl), -CONH2, -NH2, (alkyl enhamino, di(alkyl enhamino, -NH(CO(C1.4 alkyl)), -N(C1.4 alkyl)C(=O)F, C14 alkyl, C1-4 deuteroalkyl, C3-5 cycloalkyl, C2.4 alkenyl, C14 deuteroalkoxy or 5-membered heteroaryl; wherein the C1-4 alkyl group is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, C1-4 alkoxy, -NH2 and di(alkyl C14)amino.

7. The compound according to any one of Claims 1, 2, 4 and 5, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Rw is H, halogen, -CN, -CONH2, -NH2, (alkyl Ci-4)amino, di(alkyl C^amino or deuteroalkoxy Cm; wherein the alkyl group Cm is optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, alkoxy Cm, -NH2 and di(alkyl Ci-4)amino.

8. The compound according to any one of Claims 1, 2, 4 and 5, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, 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.

9. The compound according to any one of Claims 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.

10. The compound according to any one of Claims 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 C1-4 alkyl.

11. The compound according to any one of Claims 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. 306 12. The compound according to any one of Claims 1, 2, 4 and 5, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, where Rw is H.

13. The compound according to any one of Claims 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Rx is H, halogen, -OH, -CN, -CO(Cm alkyl), -S(O)n(Cm alkyl), -CONH2, -NH2, (Ci-4 alkyl)amino, di(Cm alkyl)amino, -NH(CO(Cm alkyl)), -N(Cm alkyl)C(=O)F, Ci4 alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, Cm alkoxy, Cm deuteroalkoxy, or 5-membered heteroaryl; wherein the Cm alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, -NH2, and di(Cm alkyl)amino.

14. The compound according to any one of Claims 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Rx is H, halogen, -OH, -CN, -CONH2, -NH2, (alkyl CM)amino, di(alkyl CM)amino, C1-4 alkoxy or Cm deuteroalkoxy; wherein the Cm alkyl and C1-4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, Cm alkoxy, -NH2 and di(alkyl CM)amino.

15. The compound according to any one of Claims 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, -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 1,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents selected independently from F, Cl, -OH, -CN, methoxy, -NH2 and -N(CH3)2.

16. The compound according to any one of Claims 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, 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.

17. The compound according to any one of Claims 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 307 Rx is H, halogen, -OH, -CN, -CO(Cm alkyl), -S(O)n(C1-4 alkyl), -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-5 alkylamino, -NH(CO(C1-4 alkyl)), -N(C1-4 alkyl)C(=O)F, C1-4 alkyl, C3-5 cycloalkyl, C2-4 alkenyl, C1-4 alkoxy, C1-5 deuteroalkoxy, or 5-membered heteroaryl; wherein the C1-4 alkyl and C1-4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, C1-4 alkoxy, -NH2, and di(alkyl Ci-4)amino.

18. The compound according to any one of Claims 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Rx is H, halogen, -OH, -CN, -CONH2, -NH2, (alkyl CiM)amino, di(alkyl hexamino, C1-4 alkyl, C1-4 alkoxy or Cm deuteroalkoxy; wherein the C1-4 alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, C1-4 alkoxy, -NH2 and di(alkyl hexamino.

19. The compound according to any one of Claims 1-12, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rx is H, -CN, -NH2, C1-40 alkoxy or C1-4 deuteroalkoxy.

20. The compound according to any one of Claims 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, -COMe, -SMe, -CONH2, -NH2, -NHMe, -NH(CH3)2, NH(COCH3), -N(CH3)C(=O)F, methyl, ethyl, cyclopropyl, -CH=CH2, methoxy, ethoxy, -OCD3 or 1,3-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, -NH2 and -N(CH3)2.

21. The compound according to any one of Claims 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 selected independently from F, -OH, methoxy, -NH2 and -N(CH3)2.

22. The compound according to any one of Claims 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 -OCD3. 308 23. The compound according to any one of Claims 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(C1-4 alkyl), -S(O)n(Cm alkyl), -CONH2, -NH2, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, -NH(CO(C1-4 alkyl)), -N(C1-4 alkyl)C(=O)F, C1-4 alkyl, C1-4 deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, C1-4 alkoxy, C1-4 deuteroalkoxy, or 5-membered heteroaryl; where the Cm alkyl and Ci-4 alkoxy groups are optionally substituted with 1 to 4 substituents selected independently from halogen, -OH, -CN, Cm alkoxy, -NH2 and di(alkyl CM)amino.

24. The compound according to any one of Claims 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Ry is H, F, Cl, -OH, -CN, -CONH2, -NH2, (alkyl Ci-4)amino, di(alkyl Ci-4)amino, Cm alkoxy or Cm deuteroalkoxy; wherein the C1,4 alkyl and C1,4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, Cm alkoxy, -NH2 and di(alkyl Ci-4)amino.

25. The compound according to any one of Claims 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Ry 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 1,3-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.

26. The compound according to any one of Claims 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, -NH2, -NHMe, methoxy, ethoxy or -OCD3; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents selected independently from F, -OH, methoxy, -NH2 and -N(CH3)2.

27. The compound according to any one of Claims 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(C1-4 alkyl), Ci-4 alkyl, C3-s cycloalkyl, C3-4 heterocycloalkyl, or Cm alkoxy; wherein the Cm alkyl group is optionally substituted with 1 to 4 substituents independently selected from C1-alkoxy and di(C1-4)amino. 309 28. The compound according to any one of Claims 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.

29. The compound according to any one of Claims 1-22, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H or Cl.

30. The compound according to any one of Claims 1-4 and 629, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, halogen, -OH, -CN, -CO(Cm alkyl), -S(O)n(C1.4 alkyl), -CONH2, -NH2, (Ci-4 alkyl)amino, di(Ci-4 alkyl)amino, -NH(CO(C1.4 alkyl)), -N(Ci-4 alkyl)C(=O)F, Ci4 alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, Cm alkoxy, Cm deuteroalkoxy, or 5-membered heteroaryl; where the Cm alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents selected independently from halogen, -OH, -CN, Cm alkoxy, -NH2 and di(alkyl CM)amino.

31. The compound according to any one of Claims 1-4 and 629, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Rz is H, halogen, -OH, -CN, -CONH2, -NH2, (alkyl CM)amino, di(alkyl CM)amino, alkoxy Cm or deuteroalkoxy Cm; wherein the alkyl Cm and alkoxy Cm groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, alkoxy Cm, -NH2 and di(alkyl CM)amino.

32. The compound according to any one of Claims 1-4 and 629, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, 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, -OCD3O 1,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents selected independently from F, Cl, -OH, -CN, methoxy, -NH2 and -N(CH3)2.

33. The compound according to any one of Claims 1-4 and 629, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 310 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 selected independently from F, -OH, methoxy, -NH2 and -N(CH3)2.

34. The compound according to any one of Claims 1-4 and 629, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H or alkyl Cm.

35. The compound according to any one of Claims 1-4 and 629, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H or methyl.

36. The compound according to any one of Claims 1-4 and 629, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H.

37. The compound according to Claim 1 or Claim 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 Rz or R1 ID.

38. The compound according to Claim 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(Ci-4 alkyl), -S(O)n(Ci-4 alkyl), -CONH2, -NH2, (Ci-4 alkyl)amino, di(Ci-4 alkyl)amino, -NH(CO(Ci-4 alkyl)), -N(Ci-4 alkyl)C(=O)F, C1,4 alkyl, C1-4 deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, C1 alkoxy, C2 deuteroalkoxy, or 5-membered heteroaryl; where the C1-4 alkyl and C1.4 alkoxy groups are optionally substituted with 1 to 4 substituents selected independently from halogen, -OH, -CN, C14 alkoxy, -NH2 and di(alkyl Ciu)amino.

39. The compound according to Claim 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, (alkyl Cumino, di(alkyl Ci.4)amino, C1-4 alkoxy or Ci-4 deuteroalkoxy; wherein the Cu alkyl and C1.4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, Cm alkoxy, -NH2 and di(alkyl Ci-4)amino.

40. The compound according to Claim 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(COCH3), -N(CH3)C(=O)F, methyl, ethyl, -CD3, cyclopropyl, -CH=CH2, methoxy, ethoxy, -OCD3 or 1,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents selected independently from F, Cl, -OH, -CN, methoxy, -NH2 and -N(CH3)2.

41. The compound according to Claim 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 selected independently from F, -OH, methoxy, -NH2 and -N(CH3)2.

42. The compound according to Claim 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H, F, Cl, -CN, -COO(Cm alkyl), C1-4 alkyl, C3.s cycloalkyl, C3m heterocycloalkyl, or Cm alkoxy; wherein the Cm alkyl group is optionally substituted with 1 to 4 substituents independently selected from Cm alkoxy and di(Cm alkyl)amino.

43. The compound according to Claim 37, 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.

44. The compound according to Claim 37, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Ry is H or Cl.

45. The compound according to any one of Claims 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein Rz is H, halogen, -OH, -CN, -CO(Cm alkyl), -S(O)n(C1-4 alkyl), -CONH2, -NH2, (alkyl hexamino, di(CM alkyl)amino, -NH(CO(Cm alkyl)), -N(Ci-4 alkyl)C(=O)F, C14 alkyl, Cm deuteroalkyl, C3-5 cycloalkyl, C2-4 alkenyl, Cm alkoxy, Cm deuteroalkoxy, or 5-membered heteroaryl; wherein the Cm alkyl and Cm alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, -OH, -CN, Cm alkoxy, -NH2, and di(CM alkyl)amino. 312 46. ​​The compound according to any one of Claims 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, (C1-4 alkyl)amino, di(C1-4 alkyl)amino, C1-4 alkoxy, or C1-4 deuteroalkoxy; wherein the C1-4 alkyl and C1-4 alkoxy groups are optionally substituted with 1 to 4 substituents independently selected from halogen, OH, C1-4 alkoxy, -NH2, and di(C1-4 alkyl)amino.

47. The compound according to any one of Claims 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, 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 1,3-oxazol-2-yl; wherein the methyl and methoxy groups are optionally substituted with 1 to 3 substituents selected independently from F, Cl, -OH, -CN, methoxy, -NH2 and -N(CH3)2.

48. The compound according to any one of Claims 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 selected independently from F, -OH, methoxy, -NH2 and -N(CH3)2.

49. The compound according to any one of Claims 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H, halogen, or C1-4 alkyl 50. The compound according to any one of Claims 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.

51. The compound according to any one of Claims 37-44, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein Rz is H.

52. The compound according to any one of Claims 37-51, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R1 is H, methyl, CH2F or CD3. 313 53. The compound according to any one of Claims 37-51, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R1 is H.

54. The compound according to Claim 1 or Claim 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 IE or 55. The compound according to Claim 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein x is O.

56. The compound according to Claim 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein x is NH.

57. The compound according to Claim 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein x is N(alkyl Cm).

58. The compound according to Claim 54, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, where x is NCH3.

59. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 60. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 314 61. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 62. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 63. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 64. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 65. The compound according to any one of Claims 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.

66. The compound according to any one of Claims 1-58, 64 and 65, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein B is linked through a C atom to the bicyclic core and R3 is linked through an N atom.

67. The compound according to any one of Claims 1-58, 64 and 65, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein B is linked through an N atom to the bicyclic core and R3 is linked through a C atom; 68. The compound according to any one of Claims 1-58, 64 and 65, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein B is linked through a C atom to the bicyclic core and R3 is linked through a C atom.

69. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R2 is *0- ^3¼^.

70. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 71. The compound according to any one of Claims 1-58, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R2 is 2-benzofuranyl.

72. The compound according to any one of Claims 1-71, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the portion A, A' of R2 oe| 2-benzofuranyl is further optionally substituted with a substituent R3'.

73. The compound according to any one of Claims 1-71, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the portion A, A' or of R3 or the 2-benzofuranyl is not further substituted with one or two independently selected R3' substituents.

74. The compound according to any one of Claims 1-70, 72 and 73, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein R3 is C2-6 alkyl, C1-3 alkoxy, -CH2(C3-5 cycloalkyl), -OCH2(C3-5 cycloalkyl) or phenyl; wherein the C2-6 alkyl, C1-3 alkoxy, -CH2(C3-5 cycloalkyl) and -OCH2(C3-5 cycloalkyl) groups are optionally substituted with 1 to 5 halogen atoms and are optionally substituted with -CN and wherein the phenyl is optionally substituted with a halogen substituent.

75. The compound according to any one of Claims 1-70, 72 and 73, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein R3 is C2-6 alkyl, C1-3 alkoxy or -OCH2(C3-5 cycloalkyl); wherein the C2.6 alkyl, C1.3 alkoxy and -OCH2(C3-5 cycloalkyl) groups are optionally substituted with 1 to 5 halogen atoms and are optionally substituted with -CN.

76. The compound according to any one of Claims 1-70, 72 and 73, or a tautomer thereof, or a pharmaceutically acceptable salt thereof or thereof, wherein R3 is C2.6 alkyl or C1.3 alkoxy; wherein the C2-alkyl and C1.3 alkoxy groups are optionally substituted with 3-5 halogen atoms.

77. The compound according to any one of Claims 1-70, 72 and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R3 is 2,2,2-trifluoroethyl, propyl, 2,2-difluoropropyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 2,2,3,3,3-pentafluoropropyl, -OCH2CN, -OC(CH3)2CN, difluoromethoxy, trifluoromethoxy, -OCH(CN)CH3, 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, (2,2difluorocyclopropyl)methoxy, phenyl, 3-fluorophenyl or 4-fluorophenyl.

78. The compound according to any one of Claims 1-70, 72 and 73, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein 317 R3 is 2,2-difluoropropyl, 4,4,4-trifluorobutyl, 2,2,3,3,3-pentafluoropropyl, OC(CH3)2CN, trifluoromethoxy, -OCH(CN)CH3, 2-fluoroethoxy, 2,2,-difluoroethoxy, 2,2,2-trifluoroethoxy, 2,2-difluoropropoxy, cyclopropylmethoxy or (2,2-difluorocyclopropyl)methoxy.

79. The compound according to any one of Claims 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.

80. The compound according to any one of Claims 1-72 and 7479, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R3' is independently halogen or C1-4 alkyl.

81. The compound according to any one of Claims 1-72 and 7479, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R3' is F or methyl.

82. The compound according to any one of Claims 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is C1.3 alkyl, Cu haloalkyl, Cm alkoxy or C3-5 cycloalkyl.

83. The compound according to any one of Claims 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is C1-3 haloalkyl.

84. The compound according to any one of Claims 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is methyl, ethyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, ethoxy or cyclopropyl.

85. The compound according to any one of Claims 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.

86. The compound according to any one of Claims 1-81, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein R4 is trifluoromethyl. 318 87. The compound according to any one of Claims 1-86, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein n is 0.

88. The compound according to any one of Claims 1-86, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein n is 1.

89. The compound according to any one of Claims 1-86, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein n is 2.

90. The compound of information with Reivindicación 1, or a tautómero de este, or a sal pharmaceutically acceptable of this compound or of that tautómero, where the compound is (2R)-2-(4-(8-methoxy-4-oxo-2-(tr¡fluoromet¡l)-4H-pyr¡do[1,2-a]pyrimidin-3yl)phenoxy)propanon¡tr¡lo; (2R)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyr¡mido[1,2-a]pyrimid in-3yl)phenoxy)propanonitrile; (2S)-2-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4H-pyr¡do[1,2-a]pyrimidin-3¡l)phenoxy)propanon¡tr¡lo; (2S)-2-(4-(8-methoxy-4-oxo-2-(tr¡fluoromethyl)-4H-pyr¡m¡do[1,2-a]pyrimidin-3yl)phenox¡)propanon¡trilo; (4-(8-methox¡-4-oxo-2-(trifluorometh¡l)-4H-p¡rido[1,2-a]pyr¡midi η-3-yl)-1 H-pyrazol-1yl)acetonitrile; (4-(8-methoxy-4-oxo-2-(tr¡fluoromethyl)-4H-p¡r¡do[1,2-a]pyrimid¡n-3-¡l)phenox¡)acetonitr¡lo; (4-(8-methox¡-4-oxo-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2-a]pir¡m¡d¡n-3-¡l)phen¡l)acetone¡tr¡lo; (4-(8-methox¡-4-oxo-2-(tr¡fluoromet¡l)-4H-p¡r¡m¡do[1,2-a]p¡r¡m¡d¡n-3-yl)phenoxy)acetone¡tr¡lo;(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4H-p¡rido[1,2a]pirimidin-8-il)acetonitrilo; 1-(clorometil)-7-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l]-8-(tr¡fluoromet¡l)1 H,2H,6H-p¡rimido[1,2-a][1,3]diazin-2,6-diona; 1-(fluorometil)-7-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-¡l]-8-(tr¡fluoromet¡l)1 H,2H,6H-[1,3]diazino[1,2-a]pirimidin-2,6-d¡ona; 1 -(metil-d3)-7-(4-(2,2,2-trifluoroetoxi)fenil)-8-(trifluorometil)-2H-pirimido[1,2-a]pinm¡din- 2,6 (1 H)-diona; 319 1-metil-7-[1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l]-8-(tr¡fluorometil)-1H,2H,6H[1,3]diazino[1,2-a]p¡rimid¡n-2,6-diona; 2-(4-(8-metox¡-4-oxo-2-(tnfluoromet¡l)-4H-pir¡do[1,2-a]p¡r¡m¡d¡n-3-il)fenox¡)-2metilpropanonitrilo; 2-(4-(8-metoxi-4-oxo-2-(trifluorometil)-4H-pir¡do[1,2-a]p¡r¡midin-3¡l)fenoxi)propanonitrilo; 2-(4-(8-metox¡-4-oxo-2-(trifluorometil)-4H-pir¡m¡do[1,2-a]pirimidin-3il)fenox¡)propanon¡trilo;2-(difluoromethyl)-3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-4H-pyrido[1,2a]pyrimidin-4-one; 2-(difluoromethyl)-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidine-8-carbonitrile; 2-(difluoromethyl)-8-methoxy-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 2-(difluoromethyl)-8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-8-carbonyl; 2-(fluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidine-4-one; 2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H,6H,7H,9H-pyramido[2,1c][1,4]oxazin-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-(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[1,2a]pyrimidin-4-one; 2-ethyl-8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 2-ethyl-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimidine-4-one; 2-ethyl-8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4,8(1H)-dione; 320 3-(1-(2,2-difluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-(1-(3-fluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pinimidine4-one;3-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 3-(1-(4-fluoropropyl)-1 Hp¡razol-4-yl)-8-methoxy¡-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2-a] pirimidi n4-one; 3-(1-{[(1 R )-2,2-d¡fluorocycloprop¡l]met¡l}-1H-pyrazol-4-¡l)-8-methoxy¡-2-(trifluoromet¡l)-4Hpyrido[1,2-a]pyr¡m¡d¡n-4-one; 3-(1-{[(1S)-2,2-d¡fluorocycloprop¡l]met¡l}-1H-pyrazol-4-¡l)-8-methoxy-2-(trifluoromet¡l)-4Hpyrido[1,2-a]pyrimid¡n-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-4one; 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[1,2a]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[1,2a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2a]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-pyramidal)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-(3-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-paramido[1,2a]pyrimidine-4-one; 3-(4-(((1 R)-2,2-d¡fluorocycloprop¡l)methoxy¡)phen¡l)-8-methoxy¡-2-(trifluorotriethyl)-4H-pyrido[1,2a]pyrimidin-4-one;321 3-(4-((((1 S)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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]pyrimidin-4,8(1 H)-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-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;3-(4-(2-fluoroethoxy)phenyl)-8-(methyloxy-d3)-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 3-(4-(2-fluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4l-l-pyrimido[1,2-a]pyrimidin-3-yl)-1H-pyrazol-1 yl)propanenitrile; 3-(4-(8-methoxy-4-oxo-2-(trifluoromethyl)-4l-l-pyrido[1,2-a]pyrimidin-3-yl)phenyl)propanonetrile; 3-(4-(cyclopropylmethoxy)-2-fluorophenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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-(cyclopropylmethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[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[1,2a]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,6H,7H,9Hpyrimido[2,1-c][1,4]oxazin-4-one; 322 3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrazino[1,2a]pyrimidin-4-one; 3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-[1-(cyclopropylmethyl)-1H-pyrazol-4-yl]-8-methyl-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazin-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-d¡fluorociclopropil)met¡l]-1H-pirazol-4-il}-7-fluoro-8-metoxi-2-(trifluorometil)4H-pirido[1,2-a]pirimidin-4-ona; 3-{1-[(2,2-difluorociclopropil)metil]-1H-pirazol-4-il}-8-metoxi-2-(trifluorometil)-4Hpi rido[ 1,2-a]pirimidin-4-ona; 3-{1 -[(2,2-d¡fluorociclopropil)metil]-1 H-pirazol-4-il}-8-metil-2-(trifluorometil)-4Hpirimido[1,2-b]pindazin-4-ona; 3-{1-[(3,3-difluoroc¡clobutil)metil]-1 H-pirazol-4-¡l}-8-metox¡-2-(tr¡fluorometil)-4Hpirido[1,2-a]pirimidin-4-ona; 3-{1-[(3,3-difluoroc¡clobut¡l)metil]-1H-pirazol-4-¡l}-8-metoxi-2-(trifluoiOmet¡l)-4Hpirimido[1,2-b]piridaz¡n-4-ona; 3-{1-[(3,3-d¡fluorociclobutil)met¡l]-1H-p¡razol-4-¡l}-8-met¡l-2-(tr¡fluorometil)-4Hpirimido[1,2-b]piridaz¡n-4-ona; 3-fluoro-1-metil-7-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-¡l]-8-(trifluoromet¡l)1 H,2H,6H-[1,3]diazino[1,2-a]pirimidin-2,6-diona; 4-oxo-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-il)-2-(trifluoromet¡l)-4H-pirido[1,2a]p¡rim¡d¡n-8-carbon¡tr¡lo;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-8carbonitrile; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8carboxamide; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8carboxylic acid; 4-oxo-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-7-carbonitrile; 323 7-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-8-(trifluoromethyl)-2H-pyririnido[1,2a]pyrimidine-2,6(1H)-dione; 7-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyramido[1,2-a]pyramidal-2,6(1H)-dione; 7-(4-(2,2,2-trifluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyrimido[1,2-a]pyrimidine-2,6(1H)dione; 7-(4-(2-fluoroethoxy)phenyl)-8-(trifluoromethyl)-2H-pyramido[1,2-a]pyrimidine-2,6(1H)-dione;7-(methoximet¡l)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-p¡razol-4-¡l]-2-(trifluoromet¡l)-4Hpyrido[1,2-a]pir¡m¡d¡n-4-ona; 7,8- dimethyl-2-(trifluoromethyl)-3-[1 -(3,3,3-trifluoropropyl)-1 H-pyrazol-4-yl]-4H-pyrim¡do[1,2b]pyridazin-4-ona; 7,8-dimethyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpi rim ido[1,2-b]pyridazin-4-ona; 7,9-Dimethyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrazino[1,2-a]pyrimidin-4-one; 7-chloro-2-(trifluoromethyl)-3-[1 -(3,3,3-trifluoropropyl)-1 Hp¡razol-4-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 7-chloro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-p¡razol-4-yl]-2-(tr¡fluoromethyl)-4Hpyrazino[1,2-a]pyrimidin-4-one; 7-chloro-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-yl]-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2a]pyrimid¡n-4-one; 7-chloro-8-methoxy-2-(tr¡fluoromet¡l)-3-[1-(3,3,3-trifluoroprop¡l)-1 H-pyrazol-4-yl]-4Hpyrido[1,2-a]pyrimid¡n-4-one;7-Chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 Hp¡razol-4-yl]-2-(trifluoromethyl)-4H[1,3]diazino[1,2-a]pyrimidin-4-one; 7-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(tr¡fluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 7-chloro-8-methyl-2-(trifluoromethyl)-3-[1 -(3,3,3-trifluoropropyl)-1 H-pyrazol-4-yl]-4H-p¡rido[1,2a]pyrimidin-4-one; 7-chloro-8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-parazol-4-yl]-2-(trifluoromethyl)-4Hpi rido[ 1,2-a]pyrimidin-4-one; 7-chloro-8-methyl-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(tr¡fluoromethyl)-4H-p¡r¡do[1,2-a]pyrimid¡n4-ona; 7-cyclopropyl-2-(tr¡fluoromethyl)-3-[1 -(3,3,3-trifluoropropyl)-1 H-pyrazol-4-¡l]-4H-pyr¡do[1,2a]pyrim¡din-4-one; 324 7-cyclopropyl-3-[1 -(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 7-fluoro-2-(trifluoromethyl)-3-[1 -(3,3,3-trifl uropropyl)-1 H-pyrazol-4-1]-4H-pyrido[1,2a]pyrimidin-4-one;7-fluoro-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-il]-2-(tr¡fluorometil)-4H-p¡r¡do[1,2a]pirim¡d¡n-4-ona; 7-fluoro-8-hidroxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-¡l]-2-(trifluoromet¡l)-4Hpirido[1,2-a]pirimid¡n-4-ona; 7-fluoro-8-metox¡-2-(tr¡fluoromet¡l)-3-[1-(3,3,3-trifluoroprop¡l)-1H-pirazol-4-¡l]-4Hp¡ rido[ 1,2-a]pirim¡din-4-ona; 7-fluoro-8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(trifluoromet¡l)-4H[1,3]diazino[1,2-a]pirimidin-4-ona; 7-fluoro-8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(trifluorometil)-4Hpirido[1,2-a]pirimidin-4-ona; 7-fluoro-8-metoxi-3-[4-(2,2,2-trifluoroetoxi)fen¡l]-2-(trifluorometil)-4H-pirido[1,2a]pirimidin-4-ona; 7-fluoro-8-metil-3-[1-(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(trifluoromet¡l)-4Hpirido[1,2-a]pirimidin-4-ona; 7-metoxi-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-il]-2-(trifluoromet¡l)-4H[1,3]diazino[1,2-a]pirimid¡n-4-ona;7-methox¡-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-¡l]-2-(tr¡fluoromet¡l)-4Hpyrazino[1,2-a]pinm¡din-4-one; 7-methoxy-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-yl]-2-(tr¡fluoromethyl)-4Hp¡rido[ 1,2-a]pyrimid¡n-4-one; 7-methyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1 H-pyrazol-4-yl]-4H-primido[1,2b]pyridazn-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-prazol-4-¡l]-2-(tr¡fluoromethyl)-4H[1,3]diazine[1,2-a]pyrimid¡n-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-yl]-2-(tr¡fluoromet¡l)-4Hpyrazino[1,2-a]pyrimidin-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-prazol-4-yl]-2-(trifluoromethyl)-4H-pyrdo[1,2a]pirim¡d¡n-4-one; 7-methyl-3-[1-(2,2,3,3,3-pentafluoropiOp¡l)-1H-pyrazol-4-yl]-2-(trifluoroiOmetil)-4Hpyrimido[1,2-b]pyridaz¡n-4-one; 8-((1 R)-1 -hydroxyet¡l)-3-(1 -(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl)-2-(trifluorometil)4H-pyrido[1,2-a]pyridaz¡n-4-one;325 8-((1 R)-1 -hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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-((1 S)-1 -hydroxyethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-4-one; 8-((methylsulfanyl)methoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-((R)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-4-one; 8-((S)-ethylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-4-one; 8-(1,3-oxazol-2-yl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(1-hydroxyethyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[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[1,2a]pyrimidin-4-one; 8-(2-propanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 326 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)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-(1-azetyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(chloromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(chloromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethol)-4Hpyrimido[1,2-b]pyridazine-4-one; 8-(difluoromethoxy)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(difluoromethyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one;8-(dimetilam¡no)-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-il)-2-(trifluoromet¡l)-4Hpi rido[ 1,2-a]p¡r¡mid¡n-4-ona; 8-(dimet¡lam¡no)-3-(4-(2,2,2-tr¡fluoroetox¡)fen¡l)-2-(trifluoromet¡l)-4H-pir¡do[1,2a]pir¡m¡din-4-ona; 8-(et¡lsulfinil)-3-(4-(2,2,2-tr¡fluoroetoxi)fen¡l)-2-(tr¡fluorometil)-4H-pir¡do[1,2-a]pirimidin-4ona; 8-(fluorometoxi)-2-(tr¡fluoromet¡l)-3-(1-(3,3,3-trifluoroprop¡l)-1 H-pirazol-4-il)-4Hp¡ rido[ 1,2-a]pirim¡d¡n-4-ona; 8-(fluorometox¡)-3-(4-(2,2,2-tr¡fluoroetox¡)fen¡l)-2-(trifluorometil)-4H-p¡rido[1,2a]pirimid¡n-4-ona; 8-(fluorometoxi)-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-il]-2-(trifluorometil)-4Hpi rido[ 1,2-a]pirimidin-4-ona; 8-(fluorometoxi)-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l]-2-(trifluoroniet¡l)-4Hpirim¡do[1,2-b]piridaz¡n-4-ona; 8-(fluorometil)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(trifluoromet¡l)-4Hpi rido[ 1,2-a]pirim¡din-4-ona;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)-4Hpyrido[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; 327 8-(Methoxymethyl)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-(methylamino)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin4-one; 8-(methylamino)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-paramido[1,2a]pyrimidin-4-one; 8-(methyl-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4one; 8-(methyloxl-d3)-3-(1-(2,2,3,3,3-pentafluoropropl)-1H-pyrazol-4-l)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one;8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(methyloxy-d3)-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-(methylsulfanyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(methylsulfanyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin4-one; 8-(methylsulfinyl)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(methylsulfinyl)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin4-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)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one; 328 8-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-paramido[1,2-a]pyrimidine-4one; 8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]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)-4Hpyrido[1,2-a]pyrimidin-4-one;8-Ethylene-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-hydroxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrimido[1,2-b]pyridazin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-imidazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-paramido[1,2a]pyrimidin-4-one;8-methoxy-2-(trifluoromethyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]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-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrimido[1,2b]pyridazin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[3-(3,3,3-trifluoropropyl)-1,2-oxazol-5-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[4-(3,3,3-trifluoropropyl)-1H-imidazol-1-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,3-thiazol-2-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-2-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-parado[1,2-a]pyrimidin-4-one; 329 8-Methoxy-3-(1-(2,2,2-trifluoroethyl)-1H[razol-4-[1]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 8-methoxyl-3-(1-(2,2,3,3,3-pentafluoropropl)-1H-pyrazol-4-l)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-4-one;8-methoxy-3-( 1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrimido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-Methoxy-3-(1-(4,4,4-trifluorobutyl)-1 Hpazol-4-yl)-2-(trifluoromethyl)4H-pyrimido[1,2a]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[1,2a]pyrimidine-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[1,2a]pyrimidin-4-one;8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-4-one; 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyramido[1,2-a]pyramidane-4one; 8-methoxy-3-(4-(2,2,3,3,3-pentafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-(4-(2,2,3,3-tetrafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-(4-(trifluoromethoxy)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-(trifluoromethoxy)phenyl)-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-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrimido[1,2a]pyrimidin-4-one;8-metox¡-3-(6-propil-3-pir¡din¡l)-2-(tnfluoromet¡l)-4H-pir¡do[1,2-a]pirimidin-4-ona; 330 8-metoxi-3-[1-(2,2,3,3,3-pentafluoroprop¡l)-1H-1,2,3-triazol-4-il]-2-(tr¡fluoromet¡l)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 8-metox¡-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-3-¡l]-2-(tr¡fluoromet¡l)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-il]-2-(trifluoiOmetil)-4H[1,3]diazino[1,6-a]pirimidin-4-ona; 8-metoxi-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l]-2-(tr¡fluorometil)-4Hpirimido[1,2-b]piridaz¡n-4-ona; 8-metox¡-3-[2-(2,2,2-tr¡fluoroetox¡)-1,3-t¡azol-5-il]-2-(tnfluorometil)-4H-pirido[1,2a]pirimidin-4-ona; 8-metox¡-3-[2-(2,2,2-tr¡fluoroetox¡)p¡r¡midin-5-¡l]-2-(trifluoromet¡l)-4H-[1,3]diaz¡no[1,2a]pirimid¡n-4-ona; 8-metoxi-3-[2-(2,2,2-tr¡fluoroetoxi)pirimidin-5-¡l]-2-(trifluoromet¡l)-4H-p¡rido[1,2a]pirimid¡n-4-ona; 8-metoxi-3-[2-(2,2,2-tr¡fluoroetox¡)p¡r¡midin-5-¡l]-2-(trifluoromet¡l)-4H-pirimido[1,2b]p¡ridazin-4-ona;8-methoxyl-3-[2-(2,2,3,3,3-pentafluoropropoxy)pyrimidin-5-l]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-methoxy-3-[3-(2,2,3,3,3-pentafluoropropyl)-1,2-oxazol-5-yl]-2-(trifluoromethyl)-4H[rido[1,2-a]pyrimidine-4-one; 8-methoxy-3-[4-(2,2,2-trifluoroethoxy)-1,3-tazol-2-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-[5-(2,2,2-trifluoroethoxy)-1,3-thiazol-2-yl]-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-{1-[(oxetan-3-yl)methyl]-1H-pyrazol-4-yl}-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidine-4-one; 8-methoxy-6-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidine-4-one; 8-methyl-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl]-4H-pyrimido[1,2b]pyridazin-4-one; 8-methyl-2-(trifluoromethyl)-3-[5-(3,3,3-trifluoropropyl)-1,2,4-oxadiazol-3-yl]-4H-pyrido[1,2a]pyrimidin-4-one; 8-methyl-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one;8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)4H,6H,7H,8H,9H-pyrimido[1,2-a]pyrazin-4-one; 331 8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrimido[1,2-b]pyridazin-4-one; 8-methyl-3-[2-(2,2,2-trifluoroethoxy)pyrimidin-5-yl]-2-(trifluoromethyl)-4H-pyrimido[1,2b]pyridazin-4-one; 8-methyl-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(trifluoromethyl)-4H-pyrimido[1,2-b]pyridazin-4-one; 9-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-¡l]-2-(trifluoromethyl)-4Hrido[1,2-a]pyrimidin-4-one; 9-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-¡l]-2-(trifluoromet¡l)-4Hpyrido[1,2-a]pyr¡m¡d¡n-4-one; 9-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrazino[1,2-a]pyrimidin-4-one; 4-oxo-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidine-8-carboxylate methyl;fluoruro de metil(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-il)-2(trifluorometil)-4H-pir¡do[1,2-a]pirimidin-8-il)carbamilo; N-(4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pirazol-4-¡l)-2-(tr¡fluoromet¡l)-4Hpirido[1,2-a]pinmid¡n-8-¡l)acetamida; N-(4-oxo-3-(4-(2,2,2-tr¡fluoroetox¡)fen¡l)-2-(trifluoromet¡l)-4H-p¡r¡do[1,2-a]pirimidin-8il)acetamida; N,N-d¡met¡l-4-oxo-3-(4-(2,2,2-tr¡fluoroetox¡)fen¡l)-2-(tr¡fluoromet¡l)-4H-p¡r¡do[1,2a]pirimid¡n-8-carboxam¡da; N-et¡l-4-oxo-3-(4-(2,2,2-trifluoroetox¡)fen¡l)-2-(trifluoromet¡l)-4H-pirido[1,2-a]p¡r¡m¡d¡n-8carboxamida; N-met¡l-4-oxo-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l)-2-(trifluorometil)-4Hp¡rido[ 1,2-a]p¡rimidin-8-carboxamida; o N-metil-4-oxo-3-(4-(2,2,2-trifluoroetox¡)fen¡l)-2-(trifluoromet¡l)-4H-pirido[1,2-a]pirimidin8-carboxamida.; 91. The compound of claim 1, or a tautomer hereof, 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-pyrimido[1,2-a]pyrimidine-3¡l)phenoxy)propanonitrile; (2S)-2-(4-(8-methox¡-4-oxo-2-(trifluoromet¡l)-4H-pyr¡do[1,2-a]pyrimidine-3yl)phenox¡)propanon¡trile; 2-(4-(8-methoxy-4-oxo-2-(trifluoromet¡l)-4l-l-pyr¡do[1,2-a]p¡r¡m¡d¡n-3-¡l)phenox¡)-2methylpropanonitrile; 332 2-(difluoromethyl)-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyrido[1,2-a]pyrimid¡n-4-one; 2-(fluoromet¡l)-8-methox¡-3-(4-(2,2,2-tr¡fluoroethoxy)phenyl)-4H-p¡r¡do[1,2-a]pyrine¡d¡n-4-one; 2,8-d¡methox¡-3-(4-(2,2,2-tnfluoroethox¡)phenyl)-4H-p¡r¡do[1,2-a]pyrim¡d¡n-4-one; 2-cyclopro¡l-8-methoxy-3-(4-(2,2,2-tnfluoroethoxy)phenyl)-4H-p¡r¡do[1,2-a]pyrimidine-4-one; 2-ethoxy-8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-4H-pyr¡do[1,2-a]pyrimidine-4-one; 2-et¡l-8-methox¡-3-(4-(2,2,2-tr¡fluoroethox¡)phenyl)-4H-p¡r¡do[1,2-a]pyrim¡d¡n-4-one;3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4,8(1H)-dione; 3-(1-(2,2-difluoropropyl)-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 3-(2-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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[1,2a]pyrimidin-4-one; 3-(3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrimido[1,2a]pyrimidin-4-one; 3-(4-((2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2a]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]pyrimidin-4,8(1 H)-dione;3-(4-(2,2-d¡fluoroetoxi)-2-fluorofen¡l)-8-metox¡-2-(trifluoromet¡l)-4H-p¡rido[1,2-a]pir¡m¡d¡n4-ona; 3-(4-(2,2-difluoroetox¡)fen¡l)-8-metoxi-2-(trifluorometil)-4H-pirido[1,2-a]pir¡midin-4-ona; 3-(4-(2,2-difluoropropoxi)fenil)-8-metox¡-2-(tr¡fluorometil)-4H-p¡r¡do[1,2-a]pirimidin-4ona; 3-(4-(2-fluoroetox¡)fen¡l)-8-metox¡-2-(tr¡fluorometil)-4H-p¡r¡do[1,2-a]p¡r¡midin-4-ona; 3-(4-(c¡cloprop¡lmetox¡)fen¡l)-8-metox¡-2-(trifluoromet¡l)-4H-p¡rido[1,2-a]p¡r¡m¡d¡n-4-ona; 4-oxo-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4H-p¡rido[1,2a]pirim¡d¡n-8-carbonitrilo; 4-oxo-3-(4-(2,2,2-tr¡fluoroetoxi)fenil)-2-(trifluorometil)-4H-pirido[1,2-a]pirimidin-8carboxamida; 7-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-il)-8-(trifluoromet¡l)-2H-pirim¡do[1,2a]pirimidin-2,6( 1 H)-diona; ficzQcn / zznz / q / υιλι 333 7-cloro-3-[1 -(2,2,3,3,3-pentafluoropropil)-1 H-pirazol-4-il]-2-(trifluorometil)-4H-pirido[1,2a]p¡rim¡d¡n-4-ona;7-chloro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-¡l]-2-(tr¡fluoromet¡l)-4H[1,3]diazine[1,2-a]pyrimidin-4-one; 7-fluoro-8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyr¡midin-4-one; 8-((1 R)-1-hidroxiet¡l)-3-( 1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl)-2-(trifluoromet¡l)4H-pyrido[1,2-a]p¡r¡m¡d¡n-4-ona; 8-((1S)-1-hidroxyethyl)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1 H-pyrazol-4-¡l)-2-(trifluoromet¡l)4H-pyrido[1,2-a]pir¡m¡d¡n-4-ona; 8-((dimethylam¡no)methyl)-3-(1-(2,2,3,3,3-pentafluoropiOp¡l)-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)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(dimethylam¡no)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one; 8-(fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1 H-pyrazol-4-yl]-2-(tr¡fluoromet¡l)-4Hpyrido[1,2-a]pyrimidin-4-one;8-(fluorometil)-3-(4-(2,2,2-tr¡fluoroetoxi)fenil)-2-(tr¡fluorometil)-4H-p¡r¡do[1,2-a]pirimidin4-ona; 8-(hidrox¡met¡l)-3-(1-(2,2,3,3,3-pentafluoropropil)-1H-p¡razol-4-¡l)-2-(trifluorometil)-4Hpi rido[ 1,2-a]pirim¡d¡n-4-ona; 8-(hidrox¡met¡l)-3-(4-(2,2,2-tr¡fluoroetox¡)fenil)-2-(trifluorometil)-4H-p¡r¡do[1,2-a]pirimidin4-ona; 8-(metoximetil)-3-[1-(2,2,3,3,3-pentafluoropropil)-1H-pirazol-4-il]-2-(trifluorometil)-4Hpi rido[ 1,2-a]pirimidin-4-ona; 8-(metilamino)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4Hpirido[1,2-a]pirim¡d¡n-4-ona; 8-(met¡lam¡no)-3-(4-(2,2,2-tnfluoroetox¡)fenil)-2-(tr¡fluorometil)-4H-p¡r¡do[1,2-a]pirimidin4-ona; 8-(metiloxi-d3)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4Hpi rido[ 1,2-a]pirimidin-4-ona; 8-(metilox¡-d3)-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-p¡razol-4-¡l)-2-(tr¡fluoromet¡l)-4Hpirim¡do[1,2-a]pir¡m¡din-4-ona;8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one; 334 8-(methyloxy-d3)-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[1,2a]pyrimidin-4-one; 8-amino-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[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-amino-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-paramido[1,2-a]pyrimidin-4one; 8-chloro-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-ethoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pinmidin-4-one; 8-methoxy-2-(trifluoromethyl)-3-(1-(3,3,3-trifluoropropyl)-1H-pyrazol-4-yl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrido[1,2-a]pyrimidin-4-one;8-methoxy-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hpyrimido[1,2-a]pinimidine-4-one; 8-methoxy-3-(1-(4,4,4-trifluorobutyl)-1 Hpazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyramidin-4-one; 8-methoxy-3-(2-methyl-4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-parado[1,2a]pyrimidine-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-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(4-(trifluoromethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrimido[1,2-a]pyrimidin-4-one; 8-methoxy-3-(6-(2,2,2-trifluoroethoxy)-3-pyridinyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin4-one; 8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-1,2,3-tr¡azol-4-¡l]-2-(tr¡fluoromet¡l)-4Hpyrido[1,2-a]pyrim¡d¡n-4-one; 8-methoxy-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4Hpyrimido[1,2-b]pyridazn-4-one;8-metoxi-3-[2-(2,2,2-tr¡fluoroetox¡)pirimidin-5-¡l]-2-(trifluoromet¡l)-4H-p¡rido[1,2a]pirim¡d¡n-4-ona; o 8-metoxi-3-[2-(2,2,2-tr¡fluoroetox¡)p¡nm¡d¡n-5-¡l]-2-(trifluoromet¡l)-4H-p¡rimido[1,2b]piridaz¡n-4-ona. 335; 92. The compound according to Claim 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is 4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-8-carbonitrile; 8-(methyloxy-d3)-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2a]pyrimidin-4-one; 8-amino-3-(4-(2,2,2-trifluoroethoxy¡)phen¡l)-2-(trifluoromethyl)-4H-pyr¡do[1,2-a]pyrimidín-4-one; 8-methoxy¡-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4Hp¡ rido[ 1,2-a]pinmidin-4-one; 8-methoxy¡-3-(1-(2,2,3,3,3-pentafluoroprop¡l)-1H-pyrazol-4-¡l)-2-(trifluoromethyl)-4Hpyrimido[1,2-a]pyrimidin-4-one; or 8-methoxy-3-(4-(2,2,2-trifluoroethoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one.

93. The compound according to Claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is 94. The compound according to Claim 1, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, wherein the compound is F 95. The compound according to Claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is 336 96. The compound according to Claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is An O^N^NF 97. The compound according to Claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is F 98. The compound according to Claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound is 99. A pharmaceutical composition comprising the compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, and a pharmaceutically acceptable excipient.

100. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use as a medicament.

101. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in body weight reduction.

102. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in reducing the body mass index of a subject.

103. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in the treatment of a metabolic disorder.

104. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in the treatment of a cardiovascular disorder.

105. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in the treatment of diabetes.

106. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in the treatment of obesity.

107. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in the treatment of dyslipidemia.

108. A compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 for use in the treatment of non-alcoholic steatohepatitis (NASH).

109. Use of the compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 in the preparation of a medicament for reducing the body weight or body mass index of a subject.

110. Use of the compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 in the preparation of a medicament for treating a metabolic or cardiovascular disorder.

111. Use of the compound according to any one of claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer, or the pharmaceutical composition according to claim 99 in the preparation of a medicament for treating diabetes, obesity, dyslipidemia or non-alcoholic steatohepatitis (NASH).

112. A method of reducing the body weight or 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 claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.

113. 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 claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.

114. 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 claims 1-98, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer.

115. A compound, wherein the compound is N-(3-iodo-4-oxo-2-(tr¡fluoromethyl)-4H-p¡r¡do[1,2-a]p¡rim¡d¡n-8-¡l)acetamide; 8-bromo-3-iodo-2-(trifluoromethyl)-4H-p¡r¡do[1,2-a]pyr¡midin-4-one; 8-bromo-2-(tr¡fluoromet¡l)-4H-p¡rido[1,2-a]pyrimidin-4-one; 8-hydrox¡-2-(tr¡fluoromethyl)-4H-p¡ndo[1,2-a]pyrimidin-4-one; 4-oxo-2-(tr¡fluoromethyl)-4H-p¡r¡do[1,2-a]pyr¡midin-8-carbonitnlo; 3-Iodo-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-carbonitrile; 3-bromo-8-methox¡-2-(tr¡fluoromethyl)pyr¡mide[1,2-a]pyrimidin-4-one; 8-methoxy-2-(tr¡fluoromethyl)-4H-p¡rim¡do[1,2-a]pyrimidin-4-one; or 1-(2,2,3,3,3-pentafluoropropyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.