NUCLEOTIDE HEMISULFATE SALT FOR THE TREATMENT OF HEPATITIS C VIRUS

Abstract

A hemisulfate salt of the structure: (see Formula) for treating a host infected with hepatitis C, as well as pharmaceutical compositions and dosage forms, including solid dosage forms thereof.

Description

NUCLEOTIDE HEMISULFATE SALT FOR THE TREATMENT OF HEPATITIS C VIRUS CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. provisional applications Nos. 62 / 453,437 filed on February 1, 2017; 62 / 469,912 filed on March 10, 2017; 62 / 488,366 filed on April 21, 2017; and, 62 / 575,248 filed on October 20, 2017. All of these applications are incorporated by reference. FIELD OF INVENTION The present invention is the hemisulfate salt of a selected nucleotide compound having unexpected therapeutic properties for treating a host infected with hepatitis C, as well as pharmaceutical compositions and dosage forms thereof. BACKGROUND OF THE INVENTION Hepatitis C (HCV) is a single-stranded RNA virus and a member of the genus Hepacivirus. It is estimated that 75% of all cases of liver disease are caused by HCV. HCV infection can lead to cirrhosis and liver cancer, and if left untreated, liver failure that may require a liver transplant. Approximately 71 million people worldwide are living with HCV infection, and approximately 399,000 people die each year from HCV, mostly from cirrhosis and hepatocellular carcinoma. RNA polymerase is a key target for drug development against single-stranded RNA viruses. The RNA-dependent RNA polymerase NS5B, a non-structural protein of HCV, is a key enzyme responsible for initiating and catalyzing viral RNA synthesis. There are two main subclasses of NS5B inhibitors: nucleoside analogs and non-nucleoside inhibitors (NNIs). Nucleoside analogs are anabolic to active triphosphates that act as alternative substrates for the polymerase, while NNIs bind to allosteric regions of the protein. Nucleoside or nucleotide inhibitors mimic the substrates of the natural polymerase and act as chain terminators. They inhibit the initiation of RNA transcription and the elongation of a nascent RNA chain. In addition to targeting RNA polymerase, other viral RNA proteins can also be targeted in combination therapies. For example, HCV proteins that are additional zccAnn / zznz / E / viAi targets for therapeutic approaches include NS3 / 4A (a serine protease) and NS5A (a nonstructural protein that is an essential component of HCV replicase and exerts a range of effects on cellular pathways). In December 2013, the first NS5B nucleoside polymerase inhibitor, sofosbuvir (Sovaldi®, Gilead Sciences), was approved. Sovaldi® is a uridine phosphoramidate prodrug that is taken up by hepatocytes and undergoes intracellular activation to produce the active metabolite, 2'-deoxy-2'-α-fluoro-3-C-methyluridine-5'-triphosphate. zccAnn / zznz / E / YiAi 2'-Deox¡-2'-a-fluoro^-C-met¡lur¡dine-5'-triphosphate Sovaldi® is the first medicine that has demonstrated safety and efficacy in treating certain types of HCV infection without the need for co-administration of interferon. Sovaldi® is the third medicine with a Breakthrough Therapy designation to receive FDA approval. In 2014, the U.S. FDA approved Harvoni® (ledispasvir, an NS5A inhibitor, and sofosbuvir) for the treatment of chronic hepatitis C virus Genotype 1 infection. Harvoni® is the first combination pill approved to treat chronic HCV Genotype 1 infection. It is also the first approved regimen that does not require administration with interferon or ribavirin. In addition, the FDA approved simeprevir (Olysio™) in combination with sofosbuvir (Sovaldi®) as a once-daily, all-oral, interferon-free, ribavirin-free treatment for adults with HCV Genotype 1 infection. The U.S. FDA also approved AbbVie’s VIEKIRA Pak™ in 2014, a multi-pill pack containing dasabuvir (a non-nucleoside NS5B polymerase inhibitor), ombitasvir (an NS5A inhibitor), paritaprevir (an NS3 / 4A inhibitor), and ritonavir. VIEKIRA Pak™ can be used with or without ribavirin to treat patients infected with HCV Genotype 1, including patients with compensated cirrhosis. VIEKIRA Pak™ does not require co-therapy with interferon. In July 2015, the U.S. FDA approved Technivie™ and Daklinza™ for the treatment of HCV genotype 4 and HCV genotype 3, respectively. Technivie™ (ombitasvir / paritaprevir / ritonavir) was approved for use in combination with ribavirin for the treatment of HCV genotype 4 in patients with non-scarring cirrhosis and is the first-line treatment for HCV-4-infected patients who do not require co-administration of interferon. Daklinza™ was approved for use with Sovaldi® to treat HCV genotype 3 infections. Daklinza™ is the first drug to demonstrate safety and efficacy in the treatment of HCV genotype 3 without the need for co-administration of interferon or ribavirin. In October 2015, the US FDA warned that the HCV treatments Viekira Pak and Technivie can cause serious liver injury, primarily in patients with underlying advanced liver disease, and demanded that additional safety information be added to the label. Other currently approved therapies for HCV include interferon alpha-2b or pegylated interferon alpha-2b (Pegintron®), which can be administered with ribavirin (Rebetol®), NS3 / 4A telaprevir (Incivek®, Vertex and Johnson & Johnson), boceprevir (Victrelis™, Merck), simeprevir (Olysio™, Johnson & Johnson), paritaprevir (AbbVie), Ombitasvir (AbbVie), NNI Dasabuvir (ABT-333) and Merck's Zepatier™ (a single-tablet combination of the two drugs grazoprevir and elbasvir). Additional NS5B polymerase inhibitors are currently under development. Merck is developing the uridine nucleotide prodrug MK-3682 (formerly Idenix IDX21437), and the drug is currently in Phase II combination trials. The United States patents and WO applications describing nucleoside polymerase inhibitors for the treatment of Flaviviridae, including HCV, include those filed by Idenix Pharmaceuticals (6,812,219; 6,914,054; 7,105,493; 7,138,376; 7,148,206; 7,157,441; 7,163,929; 7,169,766; 7,192,936; 7,365,057; 7,384,924; 7,456,155; 7,547,704; 7,582,618; 7,608,597; 7,608,600; 7,625,875; 7,635,689; 7,662,798; 7,824,851; 7,902,202; 7,932,240; 7,951,789; 8,193,372; 8,299,038; 8,343,937; 8,362,068; 8,507,460; 8,637,475; 8,674,085; 8,680,071; 8,691,788, 8,742,101, 8,951,985; 9,109,001; 9,243,025; US2016 / 0002281; US2013 / 0064794; WO / 2015 / 095305; WG / 2015 / 081133; WO / 2015 / 061683; WO / 2013 / 177219; WO / 2013 / 039920; WG / 2014 / 137930; WO / 2014 / 052638; WO / 2012 / 154321); Merck (6,777,395; 7,105,499; 7,125,855; 7,202,224; 7,323,449; 7,339,054; 7,534,767; 7,632,821; 7,879,815; zccAnn / zznz / E / YiAi 8,071,568; 8,148,349; 8,470,834; 8,481,712; 8,541,434; 8,697,694; 8,715,638, 9,061,041; 9,156,872 and WO / 2013 / 009737); Emory University (6,348,587; 6,911,424; 7,307,065; 7,495,006; 7,662,938; 7,772,208; 8,114,994; 8,168,583; 8,609,627; US 2014 / 0212382; and WO2014 / 1244430); Gilead Sciences / Pharmasset Inc. (7,842,672; 7,973,013; 8,008,264; 8,012,941; 8,012,942; 8,318,682; 8,324,179; 8,415,308; 8,455,451; 8,563,530; 9,045,520; 9,090,642; and 9,139,604) and (6,908,924; 6,949,522; 7,094,770; 7,211,570; 7,429,572; 7,601,820; 7,638,502; 7,718,790; 7,772,208; RE42,015; 7,919,247; 7,964,580; 8,093,380; 8,114,997; 8,173,621; 8,334,270; 8,415,322; 8,481,713; 8,492,539; 8,551,973; 8,580,765; 8,618,076; 8,629,263; 8,633,309; 8,642,756; 8,716,262; 8,716,263; 8,735,345; 8,735,372; 8,735,569; 8,759,510 and 8,765,710); Hoffman La-Roche (6,660,721), Roche (6,784,166; 7,608,599, 7,608,601 and 8,071,567);Alios BioPharma Inc. (8,895,723; 8,877,731; 8,871,737, 8,846,896, 8,772,474; 8,980,865; 9,012,427; 2010 / 0249068 WO 2014 / 100505; WO 2013 / 096680; WO 2010 / 108135), Enanta Pharmaceuticals (US 8,575,119; 8,846,638; 9,085,599; Biota (7,268,119; 7,285,658; 7,713,941; 8,119,607; 8,415,309; 8,501,699 and 8,802,840), Biocryst Pharmaceuticals (7,388,002; 7,429,571); 7,514,410; 8,133,870; 8,242,085 and 8,440,813), Inhibitex (8,759,318 and WO / 2012 / 092484), Janssen Products (8,399,429; 8,431,588, 8,481,510, 8,552,021, 8,933,052; 9,006.29 and 9,012,428) the University of Georgia Foundation (6,348,587; 7,307,065; 7,662,938; 8,168,583; 8,673,926, 8,816,074; 8,921,384 and 8,946,244), RFS Pharma, LLC (8,895,531; 8,859,595; 8,815,829;US 2014 / 0066395; US 2014 / 0235566; US 2010 / 0279969; WO / 2010 / 091386 and WO 2012 / 158811) University College Cardiff Consultants Limited (WO / 2014 / 076490, WO 2010 / 081082; WO / 2008 / 062206), Achillion Pharmaceuticals, Inc. (WO / 2014 / 169278 and WO 2014 / 169280), Cocrystal Pharma, Inc. (US 9,173,893), Katholieke Universiteit Leuven (WO 2015 / 158913), Catabasis (WO 2013 / 090420) and the University of Minnesota Reagents (WO 2006 / 004637).; Atea Pharmaceuticals, Inc. has described 3-D-2'-deoxy-2'-α-fluoro-2'3-C-substituted-2-modified-N6-(mono- and di-methyl)purine nucleotides for the treatment of HCV in U.S. Patent 9,828,410 and PCT Application WO 2016 / 144918. Atea has also described β-ϋ-2'-deoxy-2,-substituted-4,-substituted-2-N6-substituted-6-aminopurine nucleotides for the treatment of paramyxovirus and orthomyxovirus infections in US Patent 2018 / 0009836 and WO 2018 / 009623. There remains a strong medical need to develop safe, effective, and well-tolerated HCV therapies. This need is heightened by the expectation of zccAnn / zznz / E / YiAi drug resistance. More potent direct-acting antivirals could significantly shorten treatment duration and improve adherence and sustained virological response (SVR) rates in patients infected with all HCV genotypes. Therefore, an object of the present invention is to provide compounds, methods, and dosage forms for treating and / or preventing HCV infections. BRIEF DESCRIPTION OF THE INVENTION zccAnn / zznz / E / YiAi It has been surprisingly discovered that the hemisulfate salt of Compound 1, provided below as Compound 2, exhibits unexpected therapeutic properties, including improved bioavailability and target organ selectivity over its free base (Compound 1). These unexpected advantages could not have been predicted in advance. Compound 2 is, therefore, a therapeutically superior composition of matter to administer in an effective quantity to a host in need, typically a human, for the treatment of hepatitis C. Compound 2 is known as the hemisulfate salt of (S)(((2R,3R,4R,5R)-5-(2-amino-6-(methylamino)-9H-purin-9-1)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran2-1)methoxy)(phenoxy)phosphoryl)-L-alaninate. Compound 1 is described in U.S. Patent No. 9,828,410. Compound 1 Compound 2 Compound 2, like Compound 1, is the corresponding compound (Compound 1-6) in the cell, which is converted to its active nucleotide triphosphate metabolite and RNA polymerase inhibitor (see Chemical Equation 1). Because Compound 1-6 is produced in the cell and does not leave the cell, it cannot be measured in the plasma. However, the 5'-OH metabolite Compound 1-7 (see Chemical Equation 1) is exported from the cell and can therefore be measured in the plasma, serving as a proxy for the concentration of the intracellular active metabolite Compound 1-6. It has been found that the in vivo plasma concentration of the substitute Compound 1-7, and therefore the intracellular concentration of Compound 1-6, is substantially higher when Compound 2 is administered in vivo than when Compound 1 is administered in vivo. In a side-by-side comparison of dogs dosed with Compound 1 and Compound 2 (Example 19, Table 28), dosing with Compound 2 achieved an AUC (0-4 hrs) of the definitive guanine 5'-OH nucleoside metabolite (1-7) that is twice as high as the AUC after dosing with Compound 1. It is unexpected that a non-covalent salt would have such an effect on the plasma concentration of the parent drug (Compound 1). Furthermore, Compound 2 is selectively partitioned in vivo to the liver over the heart (Example 19, Table 29), which is beneficial since the liver is the organ damaged in HCV-infected hosts. Dogs were dosed with either Compound 1 or Compound 2, and the concentration of active triphosphate (1-6) was measured in the liver and heart. The liver-to-heart ratio of active triphosphate concentration was higher after dosing with Compound 2 compared to Compound 1, as shown in Table 29. Specifically, the liver-to-heart partitioning ratio for Compound 2 is 20 compared to a liver-to-heart partitioning ratio of 3.1 for Compound 1.These data unexpectedly indicate that administration of Compound 2 results in preferential distribution of the active guanine triphosphate (Compound 1-6) to the liver over the heart compared to Compound 1, thus reducing the potential for off-target effects. It was unexpected that administration of Compound 2 would significantly reduce unwanted off-target partitioning. This allows for the administration of Compound 2 at a higher dose than Compound 1, should the healthcare professional deem it necessary. Furthermore, liver and heart tissue levels of the active guanine triphosphate derivative of Compound 2 (metabolite 1-6) were measured after oral administration of Compound 2 in rats and monkeys (Example 20). High levels of active guanine triphosphate (1-6) were measured in the livers of all species tested. Importantly, non-quantifiable levels of guanine triphosphate (1-6) were measured in monkey hearts, indicating liver-specific formation of the active triphosphate. Thus, it was found that, compared to Compound 1, Compound 2 enhances the distribution of guanine triphosphate (1-6). When administered to healthy patients and those infected with hepatitis C, the zccAnn / zznz / E / YiAi Compound 2 was well tolerated after a single oral dose, and the pharmacokinetic parameters Cmax, Tmax, and AUCtot were comparable in both groups (Tables 34 and 35). As described in Example 24, a single dose of Compound 2 in HCV-infected patients resulted in significant antiviral activity. Plasma exposure of metabolite 1-7 was mostly dose-proportional over the studied range. Individual pharmacokinetic / pharmacodynamic analyses of patients administered Compound 2 showed that the viral response correlated with plasma exposure to a 1-7 metabolite of Compound 2 (Example 24, Figures 23A-23F), indicating that deep vial responses can be achieved with robust doses of Compound 2. Example 24 confirms that, as non-limiting modalities, single oral doses of 300 mg, 400 mg, and 600 mg resulted in significant antiviral activity in humans. The minimum plasma concentration of metabolite 1-7 C24 after a 600 mg dose of Compound 2 was double the minimum plasma concentration of metabolite 1-7 C24 after a 300 mg dose of Compound 2. Figure 24 and Example 25 highlight the remarkable invention provided by Compound 2 for the treatment of hepatitis C. As shown in Figure 24, the minimum steady-state plasma levels (C24,ss) of metabolite 1-7 after dosing Compound 2 in humans (600 mg QD (550 mg free base equivalent) and 450 mg QD (400 mg free base equivalent)) were predicted and compared with the EC95 of Compound 1 in vitro across the range of HCV clinical isolates to determine whether the steady-state plasma concentration is consistently higher than the EC95, which would result in high efficacy against multiple clinical isolates in vivo. The EC95 for Compound 1 is the same as the EC95 for Compound 2. For Compound 2 to be effective, the minimum steady-state plasma level of metabolite 1-7 must exceed the EC95. As shown in Figure 24, the EC95 of Compound 2 against all clinical isolates evaluated ranged from approximately 18 nM to 24 nM. As shown in Figure 24, Compound 2 at a dose of 450 mg, QD (400 mg free base equivalent) in humans, provides a predicted steady state through a minimum plasma concentration (C24,ss) of approximately 40 ng / mL. Compound 2 at a dose of 600 mg, QD (550 mg free base equivalent) in humans, provides a predicted steady state through a minimum plasma concentration (C24,ss) of approximately 50 ng / mL. Therefore, the predicted steady-state plasma concentration of the surrogate metabolite 1-7 is almost double the EC95 against all clinically evaluated isolates (even the hard-to-treat GT3a), indicating superior performance. In contrast, the EC95 of the care standard sofosbuvir nucleotide (Sovaldi) varies from 50 nM to 265 nM among all clinical HCV isolates evaluated, with an EC95 lower than the predicted steady-state concentration at the 400 mg commercial dosage for only two isolates, GT2 and GT2b. The EC95 for the 400 mg commercial dosage of sofosbuvir is higher than the predicted steady-state concentration for other clinical isolates: GTla, GTlb, GT3a, GT4a, and GT4d. The data comparing efficacy with steady-state pharmacokinetic parameters in Figure 24 clearly demonstrate the unexpected therapeutic importance of Compound 2 for the treatment of hepatitis C. In fact, the predicted steady-state plasma level (Cz4,ss) after administration of Compound 2 is predicted to be at least 2 times higher than the EC95 for all genotypes tested, and is 3 to 5 times more potent against GT2. These data indicate that Compound 2 has potent pan-genotypic antiviral activity in humans. As shown in Figure 24, the EC95 of sofosbuvir against GT1, GT3, and GT4 is greater than 100 ng / ml. So, surprisingly, Compound 2 is active against HCV in a dosage form that delivers a minimum steady-state concentration (40-50 ng-ml) that is lower than the minimum steady-state concentration (approximately 100 ng / ml) achieved by the equivalent dosage form of sofosbuvir. Therefore, in one embodiment, the invention includes a dosage form of Compound 2 that provides a minimum steady-state plasma concentration (C24,ss) of metabolite 1-7 between approximately 15-75 ng / ml, for example, 20-60 ng / ml, 25-50 ng / ml, 40-60 ng / ml, or even 40-50 ng / ml. This is unexpected considering that the steady-state concentration of the equivalent metabolite of sofosbuvir is approximately 100 ng / ml. Furthermore, Compound 2 has been found to be an unusually stable, highly soluble, non-hygroscopic salt with activity against HCV. This is surprising because several salts of Compound 1 other than the hemisulfate salt (Compound 2), including the monosulfate salt (Compound 3), are not physically stable, but rather undergo deliquescence or become gummy solids (Example 4), and are therefore unsuitable for stable solid dosage forms. Remarkably, although Compound 2 does not become gummy, it is up to 43 times more soluble in water compared to Compound 1 and up to 6 times more soluble than Compound 1 under simulated gastric fluid (SGF) conditions (Example 15). As explained in Example 16, Compound 2 remains a white solid with an RI corresponding to the reference standard for 6 months under accelerated stability conditions (40°C / 75% RH). Compound 2 is stable for 9 months under ambient (25°C / 60% RH) and refrigerator (5°C) conditions. The solid dosage forms (50 mg and 100 mg) of Compound 2 were also chemically stable under accelerated (40°C / 75% RH) and refrigerated (5°C) conditions for 6 months (Example 26). Compound 2 is stable at room temperature (25°C / 60% RH) in a solid dosage form for at least 9 months. Chemical Equation 1 provides the metabolic pathway of Compound 1 and Compound 2, which involves the initial deesterification of phosphoramidate (metabolite 1-1) to form metabolite 1-2. Metabolite 1-2 is then converted to the N6-methyl-2,6-diaminopurine-5'-monophosphate derivative (metabolite 1-3), which is in turn metabolized to S'-hydroxyl N6-methyl-2,6-diaminopurine nucleoside (metabolite 1-8) and ((2R,3R,4R,5R)-5-(2-amino-6-oxo-1,6-dihydro9H-purin-9-11)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-11)methyl dihydrogen phosphate as the 5'-monophosphate (metabolite 1-4). Metabolite 1-4 is anabolicized to the corresponding diphosphate (metabolite 1-5) and then to the active triphosphate derivative (metabolite 1-6). 5'-Triphosphate can be further metabolized to generate 2-amino-9-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-1)-1,9-dihydro6H-purin-6-one (1-7).The 1-7 metabolite can be measured in plasma and is therefore a substitute for the active triphosphate (1-6), which cannot be measured in plasma. Chemical equation 1 Compound 1 1-2 1-3 1-8 1-6 1-7 zccAnn / zznz / E / YiAi In one embodiment, the invention is Compound 2 and its use for treating hepatitis C (HCV) in a host in need, optionally in a pharmaceutically acceptable vehicle. In one aspect, Compound 2 is used as an amorphous solid. In another aspect, Compound 2 is used as a crystalline solid. The present invention further includes a non-limiting exemplary procedure for the preparation of Compound 2 comprising (i) a first step for dissolving Compound 1 in an organic solvent, for example, acetone, ethyl acetate, methanol, acetonitrile or ether, or the like, in a flask or container; (ii) loading a second flask or container with a second organic solvent, which may be the same as or different from the organic solvent in step (i), optionally cooling the second solvent to 0-10 degrees C and adding H2SO4 dropwise to the second organic solvent to create an HbSCU / organic solvent mixture; and wherein the solvent, for example, may be methanol; (iii) add dropwise the HzSOVsolvent mixture in a molar ratio of 0.5 / 1.0 from step (i) to the Compound 1 solution from step (i) at room temperature or slightly increased or decreased (e.g., 23-35 degrees C); (iv) stir the reaction of step (iii) until a precipitate of Compound 2 forms, for example at room temperature or slightly increased or decreased; (v) optionally filter the precipitate resulting from step (iv) and wash with an organic solvent; and (vi) optionally, dry the resulting Compound 2 in vacuum, optionally at an elevated temperature, for example, 55, 56, 57, 58, 59 or 60°C. In one embodiment, the organic solvent in step (i) is 3-methyl-2-pentanone. In one embodiment, the organic solvent in step (i) is ethyl isopropyl ketone. In one embodiment, the organic solvent in step (i) is methyl propionate. In one embodiment, the organic solvent in step (i) is ethyl butyrate. Despite the extensive literature on antiviral nucleosides and patent applications, Compound 2 has not been specifically described. Therefore, the present invention includes Compound 2, or a composition or dosage form thereof, as described herein. The compounds, methods, dosage forms, and compositions are provided for the treatment of a host infected with an HCV virus by administering an effective amount of Compound 2. In certain modalities, Compound 2 is administered at a dose of at least approximately 100, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 mg. In certain modalities, Compound 2 is administered for up to 12 weeks, up to 10 weeks, up to 8 weeks, up to 6 weeks, or up to 4 weeks. In alternative modalities, Compound 2 is administered for at least 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, or at least 12 weeks. In certain modalities, Compound 2 is administered at least once a day or every other day.In certain formulations, Compound 2 is administered in a dosage form that achieves a minimum steady-state plasma level (C24,ss) of metabolite 1-7 between approximately 15 and 75 ng / mL. In one formulation, Compound 2 is administered in a dosage form that achieves a minimum steady-state plasma level (C24,ss) of metabolite 1-7 between approximately 20 and 60 ng / mL. In certain formulations, Compound 2 is administered in a dosage form that achieves an AUC of metabolite 1-7 between approximately 1,200 ng*h / mL and 3,000 ng*h / mL. In one formulation, Compound 2 is administered in a dosage form that achieves an AUC of metabolite 1-7 between approximately 1,500 and 2,100 ng*h / mL. The compounds, compositions, and dosage forms can also be used to treat related conditions such as HCV antibody-positive and antigen-positive conditions, virus-based chronic liver inflammation, liver cancer resulting from advanced hepatitis C (hepatocellular carcinoma (HCC)), cirrhosis, chronic or acute hepatitis C, fulminant hepatitis C, chronic persistent hepatitis C, and HCV-based fatigue. The compound or formulations containing the compounds can also be used prophylactically to prevent or restrict the progression of clinical disease in individuals who are HCV antibody-positive or antigen-positive, or who have been exposed to hepatitis C. The present invention thus includes the following features: (a) Compound 2 as described herein; (b) prodrugs of Compound 2 (c) use of Compound 2 in the manufacture of a drug for the treatment of hepatitis C virus infection; (d) Compound 2 for use in the treatment of hepatitis C, optionally in a pharmaceutically acceptable carrier; (e) a method for manufacturing a medicament intended for therapeutic use in treating hepatitis C virus infection, characterized in that Compound 2, or a pharmaceutically acceptable salt, as described herein, is used in the manufacture; (e) a pharmaceutical formulation comprising a host-treating quantity of Compound 2 with a pharmaceutically acceptable vehicle or diluent; (f) processes for the preparation of therapeutic products containing an effective amount of Compound 2, and (g) solid dosage forms including those providing an advantageous pharmacokinetic profile; and (h) processes for the manufacture of Compound 2, as described herein. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1A is a superposition of XR.PD diffractograms of samples 1-1 (Amorphous Compound 1), 1-2 (Crystalline Compound 1) and 1-3 (Amorphous Compound 2) prior to stability studies for characterization purposes as described in Example 2 and Example 5. The x-axis is 2Theta measured in degrees and the y-axis is the intensity measured in counts. Figure IB shows the HPLC chromatograph of amorphous Compound 1 (sample 1-1) to determine purity as described in Example 2. The purity of the sample was 98.7%. The x-axis is the time measured in minutes and the y-axis is the intensity measured in counts. Figure 2A shows the HPLC chromatograph of Crystalline Compound 1 (sample 1-2) to determine purity as described in Example 2. The purity of the sample was 99.11%. The x-axis is the time measured in minutes and the y-axis is the intensity measured in counts. Figure 2B is a DSC and TGA plot of Crystalline Compound 1 (sample 1-2) before any stability study for characterization purposes as described in Example 2. The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in (W / g), and the right Y-axis is the weight measured in percent. Figure 3 is an X-ray crystallography image of Compound 1 showing the absolute stereochemistry as described in Example 2. Figure 4A is a superposition of XRPD diffractograms of samples 1-1 (Amorphous Compound 1), 1-2 (Crystalline Compound 1) and 1-3 (Amorphous Compound 2) after zccRnn / zznz / E / YiAi were stored at 25°C and 60% relative humidity for 14 days as described in Example 2. The x-axis is 2Theta measured in degrees and the y-axis is the intensity measured in counts. Figure 4B is a superposition of XRPD diffractograms of samples 1-4, 1-5, 1-6, 1-7, and 1-9 after storage at 25°C and 60% relative humidity for 7 days as described in Example 4. The x-axis is 2Theta measured in degrees and the y-axis is the intensity measured in counts. Figure 5A is a superposition of XRPD diffractograms of samples 1-4, 1-6, 1-7, and 1-9 after storage at 25°C and 60% relative humidity for 14 days as described in Example 4. The x-axis is 2Theta measured in degrees and the y-axis is the intensity measured in counts. Figure 5B is the XRPD pattern of amorphous Compound 2 (sample 1-3) as described in Example 5. The x-axis is 2Theta measured in degrees and the y-axis is intensity measured in counts. Figure 6A shows the HPLC chromatograph of amorphous Compound 2 (sample 1-3) to determine purity as described in Example 5. The purity of the sample was 99.6%. The x-axis is the time measured in minutes and the y-axis is the intensity measured in counts. Figure 6B is a DSC and TGA plot for the amorphous Compound 2 (sample 1-3) prior to any stability study for characterization purposes as described in Example 5. The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in (W / g), and the right Y-axis is the weight measured in percent. Figure 7A is a superposition of XRPD diffractograms of crystalline samples (samples 2-2, 2-6, and 2-7) and poorly crystalline samples (samples 2-3, 2-4, 2-5, and 2-8) identified from the crystallizations of Compound 2 (Example 6). The x-axis is 2Theta measured in degrees, and the intensity of the y-axis is measured in counts. Figure 7B is a superposition of XRPD diffractograms of amorphous samples (samples 2-9, 2-10, and 2-11) identified from the crystallizations of Compound 2 (Example 6). The x-axis is 2Theta measured in degrees, and the y-axis intensity is measured in counts. Figure 8A is a superposition of XRPD diffractograms of samples (samples 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, and 2-8) after 6 days of storage at 25°C and 60% relative humidity (Example 6). The x-axis is 2Theta measured in degrees and the y-axis intensity measured in counts. Figure 8B is a DSC and TGA plot for sample 2-2 (Example 6). The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in W / g, and the right Y-axis is the weight measured as a percentage. The experimental procedures for collecting DSC and TGA data are given in Example 2. Figure 9A is a DSC and TGA plot for sample 2-3 (Example 6). The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in (W / g), and the right Y-axis is the weight measured as a percentage. The experimental procedures for collecting DSC and TGA zccAnn / zznz / E / YiAi are given in Example 2. Figure 9B is a DSC and TGA plot for sample 2-4 (Example 6). The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in W / g, and the right Y-axis is the weight measured as a percentage. The experimental procedures for collecting DSC and TGA data are given in Example 2. Figure 10A is a DSC and TGA plot for sample 2-5 (Example 6). The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in W / g, and the right Y-axis is the weight measured as a percentage. The experimental procedures for collecting DSC and TGA data are given in Example 2. Figure 10B is a DSC and TGA plot for sample 2-6 (Example 6). The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in W / g, and the right Y-axis is the weight measured as a percentage. The experimental procedures for collecting DSC and TGA data are given in Example 2. Figure 11A is a DSC and TGA plot for sample 2-7 (Example 6). The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in W / g, and the right Y-axis is the weight measured as a percentage. The experimental procedures for collecting DSC and TGA data are given in Example 2. Figure 11B is a DSC and TGA plot for sample 2-8 (Example 6). The X-axis is the temperature measured in °C, the left Y-axis is the heat flux measured in W / g, and the right Y-axis is the weight measured as a percentage. The experimental procedures for collecting DSC and TGA data are given in Example 2. Figure 12A is the XRPD pattern of amorphous Compound 4 (sample 3-12) as described in Example 7. The x-axis is 2Theta measured in degrees and the y-axis is the intensity measured in counts. No crystallization of a malonate salt was observed regardless of the solvent used. Figure 12B is a superposition of XRPD diffractograms of amorphous samples (samples 3-6, 3-10, 3-11, and 3-12) identified from the attempted crystallization of compound 1 with malonate salt (Example 7). The x-axis is 2Theta measured in degrees, and the y-axis is the intensity measured in counts. Figure 13A is the HPLC chromatogram of sample 3-12 from the attempted crystallization of compound 1 with malonate salt as described in Example 7. The sample had a purity of 99.2%. The x-axis is time measured in minutes and the y-axis is intensity measured in mAu. Figure 13B is a superposition of XRPD diffractograms of solid samples obtained from crystallization using LAG (samples 4-13, 4-12, 4-9, 4-3, and 4-1) compared to zccAnn / zznz / E / YiAi Compound 1 (sample 1-2) as described in Example 8. All XRPDs match the crystalline acid counterion patterns with no additional peaks. The x-axis is 2Theta measured in degrees, and the y-axis is intensity measured in counts. Figure 14A is a superposition of XRPD diffractograms of samples obtained using ethyl acetate as the crystallization solvent (samples 6-13, 6-12, 6-11, 6-10, 6-8, 6-7, 6-6, 6-5, 6-4, and 6-2) compared to crystalline Compound 1 (sample 1-2) as described in Example 10. In general, the XRPD patterns were found to match the pattern of Compound 1, with the exception of samples 6-2, 6-4, and 6-5, which exhibited slight differences. The x-axis is 2Theta measured in degrees, and the y-axis is intensity measured in counts. Figure 14B is a superposition of the XRPD diffractogram of sample 5-1 after a second dissolution in MEK and the addition of the antisolvent cyclohexane and pamiocic acid as described in Example 9. Sample 5-1, crystallized in pamiocic acid, was a solid after maturation, but the XRPD pattern matched the pattern of pamiocic acid. Figure 15A is a superposition of XRPD diffractograms of samples obtained using ethyl acetate as the crystallization solvent (samples 6-5, 6-4, and 6-2) compared to crystalline Compound 1 (sample 1-2) as described in Example 10. In general, the XRPD patterns were found to match the pattern of Compound 1, with the exception of samples 6-2, 6-4, and 6-5, which exhibited slight differences. The x-axis is 2Theta measured in degrees, and the y-axis is the intensity measured in counts and labeled with the acid used in crystallization. Figure 15B is the XRPD pattern for Compound 2 as described in Example 14. The x-axis is 2Theta measured in degrees and the y-axis is the intensity measured in counts. Figure 16A is a graph of the concentration levels of active TP (metabolite 1-6) in the livers and hearts of rats, dogs, and monkeys (Example 18). The x-axis is the dose measured in mg / kg for each species, and the y-axis is the concentration of active TP measured in ng / g. Figure 16B is a graph of the concentration levels of active TP (metabolite 1-6) in the liver and heart of dogs (n = 2) measured 4 hours after a single oral dose of Compound 1 or Compound 2 (Example 19). The x-axis is the dose of each compound measured in mg / kg and the y-axis is the concentration of active TP measured in ng / g. Figure 17 shows the plasma profile of Compound 1 and metabolite 1-7 in rats administered a single oral dose of 500 mg / kg of Compound 2 (Example 20), measured 72 hours post-dose. The x-axis is time measured in hours and the y-axis is plasma concentration measured in ng / ml. Figure 18 is the plasma profile of Compound 1 and metabolite 1-7 in monkeys administered single oral doses of 30 mg, 100 mg, or 300 mg of Compound 2 (Example zccAnn / zznz / E / YiAi 20) Measured 72 hours after the dose. The x-axis is the time measured in hours and the y-axis is the plasma concentration measured in ng / ml. Figure 19 is a graph of EC95 measured in nM of sofosbuvir and Compound 1 versus clinical HCV isolates. EC95 values ​​for Compound 1 are 7–33 times lower than those for sofosbuvir (Example 22). The x-axis is labeled with the genotype, and the y-axis is EC95 measured in nM. Figure 20 is a graph of EC50 measured in nM of sofosbuvir and Compound 1 against laboratory strains of HCV genotypes 1a, 1b, 2a, 3a, 4a, and 5a. Compound 1 is approximately 6–11 times more potent than sofosbuvir in Genotypes 1–5 (Example 22). The x-axis is labeled with the genotype, and the y-axis is EC50 measured in nM. Figure 21 is a graph of the mean plasma concentration-time profile of Compound 1 following administration of a single dose of Compound 2 in all Part B cohorts of the study, as described in Example 24. Compound 1 was rapidly absorbed and rapidly metabolized within approximately 8 hours in all Part B cohorts. The x-axis is time measured in hours and the y-axis is the geometric mean plasma concentration measured in ng / ml. Figure 22 is a graph of the mean-time plasma concentration profile of metabolite 1-7 following administration of a single dose of Compound 2 in all Part B cohorts of the study, as described in Example 24. Metabolite 1-7 showed a sustained plasma concentration in all Part B cohorts. The x-axis is time measured in hours and the y-axis is the geometric mean plasma concentration measured in ng / ml. Figure 23A is an individual pharmacokinetic / pharmacodynamic analysis of a subject enrolled in cohort Ib as described in Example 24. Each graph shows plasma metabolite 1-7 exposure and HCV RNA reduction levels. The dashed line represents the minimum metabolite 1-7 concentration required to sustain a viral response greater than the EC95 value versus GTlb. The x-axis is time, measured in hours. The left y-axis is the plasma metabolite 1-7 concentration, measured in ng / ml, and the right y-axis is the HCV RNA reduction, measured in µg / ml. Figure 23B is an individual pharmacokinetic / pharmacodynamic analysis of a subject enrolled in cohort Ib as described in Example 24. Each graph shows plasma metabolite 1-7 exposure and HCV RNA reduction levels. The dashed line represents the minimum metabolite 1-7 concentration required to sustain a viral response greater than the EC95 value versus GTlb. The x-axis is time, measured in hours. The left y-axis is the plasma metabolite 1-7 concentration, measured in ng / ml, and the right y-axis is the HCV RNA reduction, measured in µg / ml. Figure 23C is an individual pharmacokinetic / pharmacodynamic analysis of a subject zccAnn / zznz / E / YiAi enrolled in cohort Ib as described in Example 24. Each graph shows plasma metabolite 1-7 exposure and HCV RNA reduction levels. The dashed line represents the minimum metabolite 1-7 concentration required to sustain a viral response greater than the EC95 value versus GTlb. The x-axis is time measured in hours. The left y-axis is the plasma metabolite 1-7 concentration measured in ng / ml, and the right y-axis is the HCV RNA reduction measured in 100 lU / ml. Figure 23D is an individual pharmacokinetic / pharmacodynamic analysis of a subject enrolled in cohort 3b as described in Example 24. Each graph shows plasma metabolite 1-7 exposure and HCV RNA reduction levels. The dashed line represents the minimum metabolite 1-7 concentration required to sustain a viral response greater than the EC95 value versus GTlb. The x-axis is time, measured in hours. The left y-axis is the plasma metabolite 1-7 concentration, measured in ng / ml, and the right y-axis is the HCV RNA reduction, measured in logio IU / ml. Figure 23E is an individual pharmacokinetic / pharmacodynamic analysis of a subject enrolled in cohort 3b as described in Example 24. Each graph shows plasma metabolite 1-7 exposure and HCV RNA reduction levels. The dashed line represents the minimum metabolite 1-7 concentration required to sustain a viral response greater than the EC95 value versus GTlb. The x-axis is time, measured in hours. The left y-axis is the plasma metabolite 1-7 concentration, measured in ng / ml, and the right y-axis is the HCV RNA reduction, measured in logio IU / ml. Figure 23F is an individual pharmacokinetic / pharmacodynamic analysis of a subject enrolled in cohort 3b as described in Example 24. Each graph shows plasma metabolite 1-7 exposure and HCV RNA reduction levels. The dashed line represents the minimum metabolite 1-7 concentration required to sustain a viral response greater than the EC95 value versus GTlb. The x-axis is time, measured in hours. The left y-axis is the plasma metabolite 1-7 concentration, measured in ng / ml, and the right y-axis is the HCV RNA reduction, measured in logio IU / ml. Figure 24 is a graph of the EC95 values ​​of Compound 1 and sofosbuvir against clinical isolates from HCV-infected patients GT1, GT2, GT3, and GT4. The dashed horizontal line (-----) represents the minimum steady-state concentration (C24,ss) of the sofosbuvir nucleoside after a 400 mg QD dose of sofosbuvir. The solid horizontal line (------) represents the minimum steady-state concentration (C24,ss) of metabolite 1-7 after 600 mg of Compound 2 (equivalent to 550 mg of Compound 1). The dashed horizontal line (--------) represents the minimum steady-state concentration (C24,ss) of metabolite 1-7 after 450 mg of Compound 2 (equivalent to 400 mg of Compound 1).As explained in Example 25, the predicted minimum steady-state plasma level (C24,ss) of metabolite 1-7 after 600 mg and 450 mg of Compound 2 exceeds the in vitro EC95 of Compound 1 against all clinical isolates tested. The minimum steady-state plasma level (C24,ss) of sofosbuvir exceeds the EC95 only in clinical isolates of GT2. The x-axis is labeled with the clinical isolates, and the box below the x-axis lists the EC95 values ​​for Compound 1 and sofosbuvir. The y-axis is the EC95 with respect to the clinical isolates measured in ng / mL. EC95 is expressed as a nucleoside equivalent. Sofosbuvir and Compound 2 were administered once daily (QD). Figure 25 is a flow diagram showing the manufacturing procedure for 50 mg and 100 mg tablets of Compound 2 as described in Example 26. In step 1, microcrystalline cellulose, Compound 2, lactose monohydrate, and croscarmellose sodium are filtered through a 600 μM sieve. In step 2, the contents of step 1 are loaded into a V-mixer and mixed for 5 minutes at 25 rpm. In step 3, magnesium stearate is filtered through a 600 μM sieve. In step 4, the magnesium stearate is loaded into the V-mixer containing the contents of step 2 (microcrystalline cellulose, Compound 2, lactose monohydrate, and croscarmellose sodium) and mixed for 2 minutes at 25 rpm. The common mixture is then divided for the production of 50 mg tablets and 100 mg tablets. To produce 50 mg tablets, the mixture from step 4 is compressed using standard 6 mm round concave tools.To produce 100 mg tablets, the mixture from step 4 is compressed using standard 8 mm round concave tools. The tablets are then packaged in induction-sealed HDPE bottles with desiccant-filled PP caps. Compound 2 is a hemisulfate salt that exhibits advantageous pharmacological properties over its corresponding free base for the treatment of an HCV virus DETAILED DESCRIPTION OF THE INVENTION The invention described herein is a compound, method, composition, and solid dosage form for the treatment of HCV virus infections in humans and other animal hosts, comprising the administration of an effective amount of the hemisulfate salt of (S)-(((2R,3R,4R,5R)-5-(2-amino-6-(methylamino)-9H-purin-9-11)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-11)methoxy)(phenoxy)phosphoryl)-L-alaninete (Compound 2) as described herein, optionally in a pharmaceutically acceptable vehicle. In one embodiment, Compound 2 is an amorphous solid. In another embodiment, Compound 2 is a crystalline solid. zccAnn / zznz / E / YiAi zccAnn / zznz / E / YiAi The compound, compositions, and dosage forms can also be used to treat conditions related to or occurring as a result of viral exposure to HCV. For example, the active compound can be used to treat HCV antigen- and HCV antibody-positive conditions, virus-based chronic liver inflammation, liver cancer resulting from advanced hepatitis C (e.g., hepatocellular carcinoma), cirrhosis, acute hepatitis C, fulminant hepatitis C, chronic persistent hepatitis C, and HCV-based fatigue. Active compounds and formulations can also be used to treat the range of HCV genotypes. At least six distinct HCV genotypes, each with multiple subtypes, have been identified globally. Genotypes 1–3 are prevalent worldwide, while genotypes 4, 5, and 6 are more geographically limited. Genotype 4 is common in the Middle East and Africa. Genotype 5 is found primarily in South Africa. Genotype 6 is predominantly found in Southeast Asia. Although Genotype 1 is the most common genotype in the United States, defining the genotype and subtype can help determine the appropriate treatment and its duration. For example, different genotypes respond differently to different medications, and optimal treatment times vary depending on the genotype of infection. Within genotypes, subtypes, such as Genotype a and Genotype Ib, also respond differently to treatment.Infection with one genotype does not preclude subsequent infection with a different genotype. As described in Example 22, Compound 2 is active against the range of HCV genotypes, including Genotypes 1-5. In one modality, Compound 2 is used to treat HCV Genotype 1, HCV Genotype 2, HCV Genotype 3, HCV Genotype 4, HCV Genotype 5, or HCV Genotype 6. In one modality, Compound 2 is used to treat HCV Genotype a. In one modality, Compound 2 is used to treat HCV Genotype Ib. In one modality, Compound 2 is used to treat HCV Genotype 2a. In one modality, Compound 2 is used to treat HCV Genotype 2b. In one modality, Compound 2 is used to treat HCV Genotype 3a. In one modality, Compound 2 is used to treat HCV Genotype 4a. In another modality, Compound 2 is used to treat HCV Genotype 4d. In one modality, Compound 1 or Compound 2 is used to treat HCV Genotype 5a. In one modality, Compound 1 or Compound 2 is used to treat HCV Genotype 6a. In one modality, Compound 1 or Compound 2 is used to treat HCV Genotype 6b, 6c, 6d, 6e, 6f, 6g, 6h, 6i, 6j, 6k, 6i, 6m, 6n, 6o, 6p, 6q, 6r, 6s, 6t, or 6u. As explained in Example 25 and shown in Figure 24, the predicted steady-state minimum concentration (C24,ss) of metabolite 1-7 after a 450 mg dose (400 mg free base) and a 600 mg dose (550 mg free base) of Compound 2 is approximately 40 to 50 ng / ml. This C24ss level exceeded the EC95 of Compound 1 in HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, and 4d. These data confirm that Compound 2 has potent pan-genotypic activity. This is surprising because Compound 2 achieves a lower minimum steady-state concentration (C24,ss) than the minimum steady-state concentration (C24,ss) of the sofosbuvir nucleoside metabolite after equivalent sofosbuvir dosing. The minimum steady-state concentration (C24,ss) of the corresponding sofosbuvir nucleoside metabolite is approximately 100 ng / ml, but this level only exceeds the EC95 of sofosbuvir against GT2 clinical isolates (Figure 24).Compound 2 is more potent than sofosbuvir against GT1, GT2, GT3, and GT4, and therefore allows for a dosage form that delivers a lower minimum steady-state concentration of its metabolite while remaining effective against all evaluated HCV genotypes. In one formulation, a dosage form of Compound 2 is delivered that achieves a minimum steady-state concentration of metabolite 1-7 (C24,ss) of approximately 15–75 ng / mL. In another formulation, a dosage form of Compound 2 is delivered that achieves a minimum steady-state concentration of metabolite 1-7 (C24,ss) of approximately 20–60 ng / mL, 20–50 ng / mL, or 20–40 ng / mL. In one modality, the compound, formulations, or solid dosage forms that include the compound can also be used prophylactically to prevent or slow the progression of clinical disease in individuals who are HCV antibody or antigen positive or who have been exposed to hepatitis C. In particular, Compound 2 has been found to be active against HCV and exhibits superior pharmacological and biosimilar properties compared to its freebase (Compound 1). Remarkably, Compound 2 is more bioavailable and achieves a higher AUC than Compound 1 (Example 19), and Compound 2 is more selective for the target organ, the liver, than Compound 1 (Example 19). Compound 2 is also advantageous over Compound 1 in terms of solubility and chemical stability. This is surprising because the monosulfate salt of ((S)(((2R,3R,4R,5R)-5-(2-amino-6-(methylamino)-9H-purin-9-1)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran2-1)methoxy)(phenoxy)phosphoryl)-L-alaninete (Compound 3) is unstable and exhibits the appearance of a sticky gum, whereas Compound 2, the hemisulfate salt, is a stable white solid. The hemisulfate salt, both as a solid and in a solid dosage form, is very stable for 9 months and is non-hygroscopic. zccAnn / zznz / E / YiAi Despite the volume of literature on antiviral nucleosides and patent applications, Compound 2 has not been specifically described. Compound 2 has S stereochemistry at the phosphorus atom, which has been confirmed by X-ray crystallography (Figure 3, Example 2). In alternative embodiments, Compound 2 can be used in any desired ratio of R and S phosphorus enantiomers, including pure enantiomers. In some embodiments, Compound 2 is used in a form that is at least 90% free of the opposite enantiomer, and may be at least 98%, 99%, or even 100% free of the opposite enantiomer. Unless otherwise described, an enantiomerically enriched Compound 2 is at least 90% free of the opposite enantiomer. Furthermore, in an alternative embodiment, the phosphoramidate amino acid may be in the D or L configuration, or a mixture thereof, including a racemic mixture. Unless otherwise specified, the compounds described herein are provided in the β-D configuration. In an alternative embodiment, the compounds may be provided in a β-L configuration. Similarly, any substituent group exhibiting chirality may be provided in racemic, enantiomeric, diastereomeric, or any mixture thereof. When a phosphoramidate exhibits chirality, it may be provided as a chiral phosphorus derivative R or S or a mixture thereof, including a racemic mixture. All combinations of these stereo configurations are alternative embodiments of the invention described herein. In another embodiment, at least one of the hydrogens of Compound 2 (the nucleotide or hemisulfate salt) may be replaced with deuterium. These alternative configurations include, but are not limited to: zccAnn / zznz / E / YiAi zccAnn / zznz / E / YiAi I. Hemisulfate salt ((5Ηί(2 / ?,3 / ?,4 / ?,5 / ?Τ5-(2-9ω!ηο-6Τι^6ΐΗ3ΐτιίηο')-9 / 7-ρυηη-9il)-4-fluoro- 3-hydroxy¡-4-met¡ltetrahydrofuran-2-yl)methoxy¡(phenoxy)phosphoryl)-¿-alaninate of isoproDil (Compound 2} The active compound of the invention is Compound 2, which may be provided in a pharmaceutically acceptable composition or solid dosage form. In one embodiment, Compound 2 is an amorphous solid. In another further embodiment, Compound 2 is a crystalline solid. Synthesis of Compound 2 The present invention further includes a non-limiting illustrative process for the preparation of Compound 2 comprising (i) a first step for dissolving Compound 1 in an organic solvent, for example, acetone, ethyl acetate, methanol, acetonitrile or ether, or the like, in a flask or container; (i) loading a second flask or container with a second organic solvent, which may be the same as or different from the organic solvent in step (i), optionally cooling the second solvent to 0-10 degrees C and adding H2SO4 dropwise to the second organic solvent to create an EbSCL / organic solvent mixture; and wherein the solvent, for example, may be methanol; (iii) add dropwise the ELSCU / solvent mixture in a molar ratio of 0.5 / 1.0 from step (i) to the Compound 1 solution from step (i) at room temperature or slightly increased or decreased (e.g., 23-35 degrees C); (iv) stir the reaction of step (iii) until a precipitate of Compound 2 forms, for example at room temperature or slightly increased or decreased; (v) optionally filter the precipitate resulting from step (iv) and wash with an organic solvent; and (vi) optionally, dry the resulting Compound 2 in vacuum, optionally at an elevated temperature, for example, 55, 56, 57, 58, 59 or 60°C. In certain embodiments, step (i) above is carried out in acetone. Furthermore, the second organic solvent in step (i) may be, for example, methanol, and the mixture of organic solvents in step (v) is methanol / acetone. In one embodiment, Compound 1 is dissolved in ethyl acetate in step (i). In one embodiment, Compound 1 is dissolved in tetrahydrogenase in step (i). In one embodiment, Compound 1 is dissolved in acetonitrile in step (i). In a further embodiment, Compound 1 is dissolved in dimethylformamide in step (i). In one embodiment, the second organic solvent in step (ii) is ethanol. In one embodiment, the second organic solvent in step (ii) is isopropanol. In one embodiment, the second organic solvent in step (ii) is n-butanol. In one embodiment, a solvent mixture is used for washing in step (v), for example, ethanol / acetone. In one embodiment, the solvent mixture for washing in step (v) is isopropanol / acetone. In one embodiment, the solvent mixture for washing in step (v) is n-butanol / acetone. In one embodiment, the solvent mixture for washing in step (v) is ethanol / ethyl acetate. In one embodiment, the solvent mixture for washing in step (v) is isopropanol / ethyl acetate. In one embodiment, the solvent mixture for washing in step (v) is n-butanol / ethyl acetate. In one embodiment, the solvent mixture for washing in step (v) is ethanol / tetrahydrofuran. In one embodiment, the solvent mixture for washing in step (v) is isopropanol / tetrahydrofuran. In one embodiment, the solvent mixture for washing in step (v) is n-butanol / tetrahydrofuran. In another embodiment, the solvent mixture for washing in step (v) is ethanol / acetonitrile.In one embodiment, the washing solvent mixture in step (v) is isopropanol / acetonitrile. In one embodiment, the washing solvent mixture in step (v) is n-butanol / acetonitrile. In one embodiment, the washing solvent mixture in step (v) is ethanol / dimethylformamide. In one embodiment, the washing solvent mixture in step (v) is isopropanol / dimethylformamide. In one embodiment, the washing solvent mixture in step (v) is n-butanol / dimethylformamide. zccAnn / zznz / E / YiAi II. Metabolism of isopropyl ((5)-(((2 / ?,37?,4 / ?,5 / ?)-5-(2-am¡no-6-(methlam¡no)-9 / / -purin-9-¡l)-4fluoro-3-hydroxy¡-4-methyltetrahydrofuran-2-¡l)methoxy)(phenoxy¡)phosphor¡l)-¿-alaninate (Compound 2) The metabolism of Compound 1 and Compound 2 involves the production of a 5'-monophosphate and the subsequent anabolism of the base N6-methyl-2,6-diaminopurine (1-3) to generate dihydrogen phosphate from ((2 / ?,3 / ?,4 / ?,5 / ?)-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-1)methyl (1-4) as the 5'-monophosphate. The monophosphate is further anabolized to the active triphosphate species: the 5'-triphosphate (1-6). The 5'-triphosphate can be further metabolized to generate 2-amino-9-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-1,9-dihydro-6H-purin-6-one (1-7). Alternatively, the 5'-monophosphate 1-2 can be metabolized to generate the purine base 1-8. The metabolic pathway for isopropyl ((S)-(((2 / ?,3 / ?,4 / ?,5 / ?)5-(2-amino-6-(methlam¡no)-9 / Apur¡n-9-¡l)-4-fluoro-3-hydrox¡-4-methyltetrah¡drofuran-2¡l)methoxy)(phenoxy¡)phosphor¡l)-¿-alaninate is illustrated in Eq. chemistry 1 (shown before). zccAnn / zznz / E / YiAi III. Additional Salts of Compound 1 In alternative embodiments, the present invention provides Compound 1 as an oxalate salt (Compound 4) or an HCl salt (Compound 5). Both the 1:1 oxalate salt and the 1:1 HCl salt have solids with properties suitable for solid dosage forms for treating a host, such as a human with hepatitis C. However, the oxalate salt may be less desirable, and perhaps unsuitable, if the patient is susceptible to kidney stones. The HCl salt is more hygroscopic than the hemisulfate salt. Therefore, the hemisulfate salt remains the more desirable salt form of Compound 1 with unexpected properties. IV. Definitions The term D configuration as used in the context of the present invention refers to the principal configuration that limits the natural configuration of sugar radicals as opposed to non-natural nucleosides or the L configuration. The term β or β anomer is used with reference to nucleoside analogues in which the nucleoside base is configured (arranged) on the plane of the furanose radical in the nucleoside analogue. The terms co-administrator and co-administration or combination therapy are used to describe the administration of Compound 2 according to the present invention in combination with at least one other active agent, for example, when appropriate, at least one additional anti-HCV agent. The timing of co-administration is best determined by the treating physician. Sometimes it is preferred that the agents be administered at the same time. Alternatively, the drugs selected for combination therapy may be administered to the patient at different times. Of course, when there is more than one viral infection or other condition, the present compounds may be combined with other agents to treat that other infection or condition as required. The term host, as used herein, refers to a unicellular or multicellular organism in which an HCV virus can replicate, including cell lines and animals, and typically a human. The term host specifically refers to infected cells, cells transfected with all or part of the HCV genome, and animals, particularly primates (including chimpanzees) and humans. In most animal applications of the present invention, the host is a human patient. Veterinary applications, in certain indications, however, are clearly provided for by the present invention (such as chimpanzees). The host may be, for example, bovine, equine, avian, canine, feline, etc. Isotopic replacement The present invention includes compounds and the use of Compound 2 with desired isotopic substitutions of atoms in amounts above the natural abundance of the isotope, i.e., enriched. Isotopes are atoms that have the same atomic number but different mass numbers, i.e., the same number of protons but a different number of neutrons. By way of general example and without limitation, hydrogen isotopes, e.g., deuterium (²H) and tritium (³H), may be used anywhere in the described structures. Alternatively or in addition, carbon isotopes, e.g., ¹³C and ¹⁴C, may be used. A preferred isotopic substitution is deuterium for hydrogen at one or more locations in the molecule to enhance drug performance. Deuterium can bind at a bond-breaking location during metabolism (an α-deuterium kinetic isotope effect) close to, or near, the bond-breaking site (a β-deuterium kinetic isotope effect).Achillion Pharmaceuticals, Inc. (WO / 2014 / 169278 and WO / 2014 / 169280) describes nucleotide deuteration to improve its pharmacokinetics or pharmacodynamics, including at position 5 of the molecule. Substitution with isotopes such as deuterium can provide certain therapeutic advantages resulting from increased metabolic stability, such as an increased in vivo half-life or reduced dosage requirements. Substituting hydrogen with deuterium at a site of metabolic breakdown can reduce or eliminate metabolism at that bond. At any position in the compound where a hydrogen atom may be present, the hydrogen atom can be any isotope of hydrogen, including protium (CH), deuterium (2H), and tritium (3H). Therefore, reference herein to a compound includes all potential isotopic forms unless the context clearly dictates otherwise. The term isotopically labeled analogue refers to an analogue that is a deuterated analogue, a 13C-labeled analogue, or a deuterated / 13C-labeled analogue. The term deuterated analogue means a compound described herein in which an H isotope, i.e., hydrogen / protium (see XH), is substituted with an H isotope, i.e., deuterium (2H). The deuterium substitution may be partial or complete. Partial deuterium substitution means that at least one hydrogen atom is substituted with at least one deuterium atom. In certain embodiments, the isotope is 90, 95, or 99% or more enriched in an isotope at any location of interest. In some embodiments, the deuterium is 90, 95, or 99% enriched at a desired location. Unless otherwise stated, the deuteration is at least 80% at the selected location. Nucleoside deuteration can occur at any replaceable hydrogen that provides the desired results. V. Treatment or prophylaxis methods Treatment, as used in this document, refers to the administration of Compound 2 to a host, e.g., a human who is, or may be, infected with an HCV virus. The term prophylactic or preventive, when used, refers to the administration of Compound 2 to prevent or reduce the likelihood of a viral disorder occurring. The present invention includes both prophylactic or preventive treatments and therapies. In one embodiment, Compound 2 is administered to a host who has been exposed to, and is therefore at risk of, infection with the hepatitis C virus. The invention relates to a method of treating or prophylizing a hepatitis C virus, including drug-resistant and multidrug-resistant forms of HCV, and to disease states, conditions, or complications related to HCV infection, including cirrhosis and related hepatotoxicities, as well as other conditions secondary to HCV infection, such as weakness, loss of appetite, weight loss, enlarged breasts (especially in men), rash (especially on the palms of the hands), impaired blood clotting, spider veins in the skin, confusion, coma (encephalopathy), fluid accumulation in the abdominal cavity (ascites), esophageal varices, portal hypertension, renal failure, enlarged spleen, decreased blood cells, anemia, thrombocytopenia, jaundice, and hepatocellular carcinoma, among others.The method comprises administering to a host in need, typically a human, an effective amount of Compound 2 as described herein, optionally in combination with at least one additional bioactive agent, e.g., an additional anti-HCV agent, further in combination with a pharmaceutically acceptable carrier additive and / or excipient. In another aspect, the present invention is a method for the prevention or prophylaxis of an HCV infection or a related disease state or condition or complication of an HCV infection, including cirrhosis and related hepatotoxicities, weakness, loss of appetite, weight loss, breast enlargement (especially in men), rash (especially on the palms of the hands), difficulty clotting blood, spider veins in the skin, confusion, coma (encephalopathy), fluid accumulation in the abdominal cavity (ascites), esophageal varices, portal hypertension, renal failure, enlarged spleen, decreased blood cells, anemia, thrombocytopenia, jaundice, and hepatocellular (liver) cancer, among others. This method comprises administering to an at-risk patient an effective amount of Compound 2 as described above in combination with a vehicle.pharmaceutically acceptable additive or excipient, optionally in combination with another anti-HCV agent. In another embodiment, the active compounds of the invention can be administered to a patient after a hepatitis-related liver transplant to protect the new organ. In an alternative embodiment, Compound 2 is provided as the hemisulfate salt of a phosphoramidate of Compound 1 other than the specific phosphoramidate described in the compound illustration. Those skilled in the art are familiar with a wide range of phosphoramidates, including various esters and phosphoesters, any combination of which may be used to provide an active compound as described herein in the form of a hemisulfate salt. VI. Pharmaceutical compositions and dosage forms In one aspect of the invention, the pharmaceutical compositions according to the present invention comprise an effective amount against the HCV virus of Compound 2 as described herein, optionally in combination with a pharmaceutically acceptable vehicle, additive, or excipient, and further optionally in combination or alternation with at least one other active compound. In one embodiment, the invention includes a solid dosage form zccAnn / zznz / E / YiAi of Compound 2 in a pharmaceutically acceptable carrier. In one aspect of the invention, the pharmaceutical compositions according to the present invention comprise an effective anti-HCV amount of Compound 2 described herein, optionally in combination with a pharmaceutically acceptable vehicle, additive or excipient, further optionally in combination with at least one other antiviral agent, such as an anti-HCV agent. The invention includes pharmaceutical compositions comprising an effective amount for treating hepatitis C virus infection of Compound 2 of the present invention or prodrug, in a pharmaceutically acceptable vehicle or excipient. In an alternative embodiment, the invention includes pharmaceutical compositions comprising an effective amount for preventing hepatitis C virus infection of Compound 2 of the present invention or prodrug, in a pharmaceutically acceptable vehicle or excipient. A person skilled in the technique will recognize that a therapeutically effective amount will vary with the infection or condition being treated, its severity, the treatment regimen to be used, the pharmacokinetics of the agent used, as well as the patient or subject (animal or human) to be treated, and such a therapeutic amount may be determined by the attending physician or specialist. Compound 2 according to the present invention can be formulated in a mixture with a pharmaceutically acceptable vehicle. In general, it is preferable to administer the pharmaceutical composition in an orally administerable form, and in particular, a solid dosage form, such as a pill or tablet. Certain formulations can be administered parenterally, intravenously, intramuscularly, topically, transdermally, buccally, subcutaneously, by suppository, or by other routes, including intranasal spray. Intravenous and intramuscular formulations are often administered in sterile saline solution. A person skilled in the art can modify the formulations to make them more soluble in water or another vehicle; for example, this can be easily achieved by minor modifications (salt formulation, esterification, etc.) that are well within the usual scope of practice.It is also within the ability of routine practitioners to modify the route of administration and regimen of Compound 2 to manage the pharmacokinetics of the present compounds to achieve a maximum beneficial effect in patients, as described in more detail here. In certain pharmaceutical dosage forms, the prodrug form of compounds, especially adiate derivatives (acetylated or otherwise), and ethers (alkyl and related), phosphate esters, thiophosphoramidates, phosphoramidates, and various salt forms of these compounds, can be used to achieve the desired effect. A person skilled in the art will recognize how to readily modify these compounds into prodrug forms to facilitate the delivery of active compounds to a target site within the host organism or patient. The person skilled in the art will also take advantage of the favorable pharmacokinetic parameters of the prodrug forms, where appropriate, when administering these compounds to a target site within the host organism or patient to maximize the desired effect of the compound. The amount of Compound 2 included within the therapeutically active formulation according to the present invention is an effective amount to achieve the desired result according to the present invention, for example, to treat HCV infection, reduce the likelihood of HCV infection, or inhibit, reduce, and / or suppress HCV or its side effects, including disease states, conditions, and / or complications that occur as a consequence of HCV. In general, a therapeutically effective amount of the present compound in a pharmaceutical dosage form may range from approximately 0.001 mg / kg to approximately 100 mg / kg per day or more, more often slightly less than approximately 0.1 mg / kg to more than approximately 25 mg / kg per day of the patient or considerably more, depending on the compound used, the condition or infection treated, and the route of administration.Compound 2 is often administered in amounts ranging from approximately 0.1 mg / kg to approximately 15 mg / kg per day, depending on the pharmacokinetics of the agent in the patient. This dosage range generally produces effective blood concentrations of the active compound that can vary from approximately 0.001 to approximately 100 micrograms / cc of blood in the patient. Often, to treat, prevent, or delay the onset of these infections and / or reduce the likelihood of an HCV virus infection, or a secondary pathological state, condition, or complication of HCV, Compound 2 will be administered in a dosage form in an amount ranging from approximately 250 micrograms to approximately 800 milligrams or more at least once a day, for example, at least approximately 5, 10, 20, 25, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, or 800 milligrams or more, one, two, three, or up to four times a day, according to the prescription of the health care professional. Compound 2 is often administered orally, but it can be administered parenterally, topically, or as a suppository, as well as intranasally, as a nasal spray, or as otherwise described herein.More generally, Compound 2 can be administered in a tablet, capsule, injection, intravenous formulation, suspension, liquid, emulsion, implant, particle, sphere, cream, ointment, suppository, inhalable form, transdermal form, buccal, sublingual, topical, gel, mucosal, and the like. When a dosage form herein is dosed at a weight dose in milligrams, it refers to the amount of Compound 2 (i.e., the weight of the hemisulfate salt) unless otherwise specified. zccAnn / zznz / E / YiAi In certain formulations, the pharmaceutical composition is in a dosage form containing from approximately 1 mg to approximately 2000 mg, from approximately 10 mg to approximately 1000 mg, from approximately 100 mg to approximately 800 mg, from approximately 200 mg to approximately 600 mg, from approximately 300 mg to approximately 500 mg, or from approximately 400 mg to approximately 450 mg of Compound 2 in a unit dosage form. In certain modalities, the pharmaceutical composition is in a dosage form, for example, in a solid dosage form, containing up to approximately 10, approximately 50, approximately 100, approximately 125, approximately 150, approximately 200, approximately 225, approximately 250, approximately 275, approximately 300, approximately 325, approximately 350, approximately 375, approximately 400, approximately 425, approximately 450, approximately 475,approximately 500, approximately 525, approximately 550, approximately 575, approximately 600, approximately 625, approximately 650, approximately 675, approximately 700, approximately 725, approximately 750, approximately 775, approximately 800, approximately 825, approximately 850, approximately 875, approximately 900, approximately 925, approximately 950, approximately 975, or approximately 1000 mg or more of Compound 2 in a unit dosage form. In one embodiment, the Compound is administered in a dosage form that delivers at least approximately 300 mg. In one embodiment, Compound 2 is administered in a dosage form that delivers at least approximately 400 mg. In one embodiment, Compound 2 is administered in a dosage form that delivers at least approximately 500 mg. In one embodiment,Compound 2 is administered in a dosage form that delivers at least approximately 600 mg. In one modality, Compound 2 is administered in a dosage form that delivers at least approximately 700 mg. In one modality, Compound 2 is administered in a dosage form that delivers at least approximately 800 mg. In certain modalities, Compound 2 is administered at least once daily for up to 12 weeks. In certain modalities, Compound 2 is administered at least once daily for up to 10 weeks. In certain modalities, Compound 2 is administered at least once daily for up to 8 weeks. In certain modalities, Compound 2 is administered at least once daily for up to 6 weeks. In certain modalities, Compound 2 is administered at least once daily for up to 4 weeks. In certain modalities, Compound 2 is administered at least once daily for up to 4 weeks. In certain modalities,Compound 2 is administered at least once for up to 6 weeks. In certain regimens, Compound 2 is administered at least once for up to 8 weeks. In certain regimens, Compound 2 is administered at least once for up to 10 weeks. In certain regimens, Compound 2 is administered at least once for up to 12 weeks. In certain regimens, Compound 2 is administered at least every other day for up to 12 weeks, up to 10 weeks, up to 8 weeks, up to 6 weeks, or up to 4 weeks. In certain regimens, Compound 2 is administered at least every other day for up to 4 weeks, at least 6 weeks, at least 8 weeks, at least 10 weeks, or at least 12 weeks. In one regimen, at least approximately 600 mg of Compound 2 is administered at least once daily for up to 6 weeks. In one regimen, at least approximately 500 mg of Compound 2 is administered at least once daily for up to 6 weeks. In one modality,At least approximately 400 mg of Compound 2 is administered at least once daily for up to 6 weeks. In one modality, at least approximately 300 mg of Compound 2 is administered at least once daily for up to 6 weeks. In one modality, at least approximately 200 mg of Compound 2 is administered at least once daily for up to 6 weeks. In one modality, at least approximately 100 mg of Compound 2 is administered at least once daily for up to 6 weeks. Metabolite 1-6 is the active triphosphate of Compound 2, but metabolite 1-6 cannot be measured in plasma. A surrogate for metabolite 1-6 is metabolite 1-7. Metabolite 1-7 is a nucleoside metabolite measurable in plasma and is therefore an indication of intracellular concentrations of metabolite 1-6. For maximum antiviral activity against HCV, a dosage form of Compound 2 must achieve a minimum steady-state concentration of metabolite 1-7 (C24,ss) that exceeds the EC95 value of Compound 2. As shown in Figure 24, the EC95 of Compound 1 against clinical swabs from GT1, GT2, GT3, and GT4 is less than 25 ng / mL (the EC95 values ​​of Compound 1 and Compound 2 are the same). In one modality, a dosage form of Compound 2 is supplied that achieves a minimum steady-state concentration (C24,ss) of metabolite 1-7 that is between approximately 15 and 75 ng / ml.In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state (C24,ss) concentration of metabolite 1-7 between approximately 20 and 60 ng / ml. In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state (C24,55) concentration of metabolite 1-7 between approximately 30 and 60 ng / ml. In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state (C24,ss) concentration of metabolite 1-7 between approximately 20 and 50 ng / ml. In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state (C24,ss) concentration of metabolite 1-7 between approximately 30 and 50 ng / ml.In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state concentration (C24,ss) of metabolite 1-7 between approximately 20 and 45 ng / ml. In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state concentration (C24,ss) of metabolite 1-7 between approximately 20 and 30 ng / ml. In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state concentration (C24,ss) of metabolite 1-7 between approximately 20 and 35 ng / ml. In one embodiment, a dosage form of Compound 2 is delivered that achieves a minimum steady-state concentration (C24,ss) of metabolite 1-7 between approximately 20 and 25 ng / ml. Approximately, the dosage forms are + 10% of the minimum steady-state concentration. In one embodiment, Compound 2 is dosed in an amount that achieves an AUC (area under the curve) of metabolite 1-7 of between approximately 1,200 and 3,000 ng / ml. In one embodiment, Compound 2 is dosed in an amount that achieves an AUC of metabolite 1-7 of between approximately 1,500 and 3,000 ng / ml. In one embodiment, Compound 2 is dosed in an amount that achieves an AUC of metabolite 1-7 of between approximately 1,800 and 3,000 ng / ml. In one embodiment, Compound 2 is dosed in an amount that achieves an AUC of metabolite 1-7 of between approximately 2,100 and 3,000 ng / ml. In a preferred embodiment, Compound 2 is dosed in an amount that achieves an AUC of metabolite 1-7 of approximately 2,200 ng*h / ml. Approximately, the dosage forms are +10% of the AUC. In the case of co-administration of Compound 2 in combination with another anti-HCV compound as otherwise described herein, the amount of Compound 2 according to the present invention to be administered ranges from approximately 0.01 mg / kg of the patient to approximately 800 mg / kg or more of the patient, or considerably more, depending on the second agent to be co-administered and its potency against the virus, the patient's condition and the severity of the disease or infection to be treated, and the route of administration. The other anti-HCV agent may be administered, for example, in amounts ranging from approximately 0.01 mg / kg to approximately 800 mg / kg.Examples of dosage amounts for the second active agent range from approximately 250 micrograms to approximately 750 mg or more at least once daily; for example, at least approximately 5, 10, 20, 25, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 600, 700, or 800 milligrams or more, up to four times daily. In certain preferred regimens, Compound 2 may often be administered in amounts ranging from approximately 0.5 mg / kg to approximately 50 mg / kg or more (generally up to approximately 100 mg / kg), generally depending on the pharmacokinetics of the two agents in the patient. These dosage intervals generally produce effective blood concentrations of the active compound in the patient. For the purposes of the present invention, a prophylactically or preventively effective amount of the compositions according to the present invention is within the same concentration range as set forth above for a therapeutically effective amount and is usually the same as a therapeutically effective amount. zccAnn / zznz / E / YiAi The administration of Compound 2 can vary from continuous administration (intravenous drip) to multiple oral or intranasal administrations per day (e.g., QID) or transdermal administration and may include oral, topical, parenteral, intramuscular, intravenous, subcutaneous, transdermal (which may include a penetration-enhancing agent), buccal, and suppository administration, among other routes. Enteric-coated oral tablets may also be used to improve the bioavailability of the compound for oral administration. The most effective dosage form will depend on the bioavailability / pharmacokinetics of the particular agent chosen, as well as the severity of the patient's condition. Oral dosage forms are particularly preferred due to ease of administration and potentially favorable patient compliance. To prepare the pharmaceutical compositions according to the present invention, a therapeutically effective amount of Compound 2 according to the present invention is often intimately mixed with a pharmaceutically acceptable vehicle according to conventional pharmaceutical compounding techniques to produce a dose. A carrier can take a wide variety of forms depending on the desired form of administration, for example, oral or parenteral. In the preparation of pharmaceutical compositions in oral dosage form, any of the usual pharmaceutical carriers can be used. Therefore, for liquid oral preparations such as suspensions, elixirs, and solutions, suitable vehicles and additives can be used, including water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like.For solid oral preparations such as powders, tablets, capsules, and solid preparations such as suppositories, suitable carriers and additives, including starches, sugar carriers such as dextrose, mannitol, lactose, and related carriers, diluents, granulating agents, lubricants, binders, disintegrating agents, and the like, may be used. If desired, tablets or capsules may be enteric-coated or sustained using standard techniques. The use of these dosage forms can significantly improve the bioavailability of the compounds in the patient. For parenteral formulations, the vehicle will usually comprise sterile water or an aqueous solution of sodium chloride, although other ingredients, including those that aid dispersion, may also be included. Of course, when sterile water is used and maintained sterile, the compositions and vehicles must also be sterilized. Injectable suspensions may also be prepared, in which case appropriate liquid vehicles, suspending agents, and the like may be used. Liposomal suspensions (including liposomes targeting viral antigens) can also be prepared using conventional methods to produce pharmaceutically acceptable vehicles. This may be appropriate for the delivery of free nucleosides, acyl / alkyl nucleosides, or phosphate ester prodrug forms of the nucleoside compounds according to the present invention. In typical embodiments according to the present invention, Compound 2 and the described compositions are used to treat, prevent, or delay an HCV infection or a secondary pathological state, condition, or complication of HCV. VIL Combination and alternating therapy It is well known that drug-resistant viral variants can emerge after prolonged treatment with an antiviral agent. Drug resistance sometimes occurs due to mutation in a gene that encodes an enzyme used in viral replication. The efficacy of a drug against an HCV infection can be prolonged, increased, or restored by administering the compound in combination with, or alternating with, another, and perhaps even two or three additional antiviral compounds that induce a different mutation or act through a different pathway, starting from the same pharmacological principle. Alternatively, the pharmacokinetics, biological distribution, half-life, or other parameters of the drug may be altered with such combination therapy (which may include alternating therapy if considered concerted).Since the described Compound 2 is an NS5B polymerase inhibitor, it may be useful to administer the compound to a host in combination with, for example, a (1) Protease Inhibitor, such as an NS3 / 4A protease inhibitor; (2) NS5A inhibitor; (3) Another NS5B polymerase inhibitor; (4) Non-substrate NS5B inhibitor; (5) They inferred alpha-2a, which may be pegylated or otherwise modified, and / or ribavirin; (6) Non-substrate-based inhibitor; (7) Helicase inhibitor; (8) Antisense oligodeoxynucleotide (S-ODN); (9) Aptamer; (10) Nuclease-resistant ribozyme; (11) RNAi, including microRNA and RNAsi; (12) Antibody, partial antibody or domain antibody to the virus, or (13) Viral antigen or partial antigen that induces an antibody response from the host. Non-limiting examples of anti-HCV agents that may be administered in combination with Compound 2 of the invention, alone or with multiple drugs from this list, are zccAnn / zznz / E / YiAi (i) protease inhibitors such as telaprevir (Incivek®), boceprevir (Victrelis™), simeprevir (Olysio™), paritaprevir (ABT-450), glecaprevir (ABT-493), ritonavir (Norvir), ACH-2684, AZD-7295, BMS-791325, danoprevir, Filibuvir, GS-9256, GS-9451, MK-5172, Setrobuvir, Sovaprevir, Tegobuvir, VX-135, VX-222, and, ALS-220; (i) NS5A inhibitor such as ACH-2928, ACH-3102, IDX-719, daclatasvir, ledispasvir, velpatasvir (Epclusa), elbasvir (MK-8742), grazoprevir (MK-5172), and Ombitasvir (ABT-267); (iii) NS5B inhibitors such as AZD-7295, Clemizole, dasabuvir (Exviera), ITX5061, PPI-461, PPI-688, sofosbuvir (Sovaldi®), MK-3682, and mericitabine; (iv) NS5B inhibitors such as ABT-333, and MBX-700; (v) Antibody such as GS-6624; (vi) Fármacos combinados como Harvoni (ledipasvir / sofosbuvir); Viekira Pak (ombitasvir / paritaprevir / ritonavir / dasabuvir); Viekirax (ombitasvir / paritaprevir / ritonavir); G / P (paritaprevir y glecaprevir); Technivie (ombitasvir / pa rita previ r / ritonavir) y Epclusa (sofosbuvir / velpatasvir) y Zepatier (elbasvir y grazoprevir). If Compound 2 is administered to treat advanced hepatitis C virus leading to liver cancer or cirrhosis, in one modality, the compound may be administered in combination or alternation with another drug typically used to treat hepatocellular carcinoma (HCC), for example, as described by Andrew Zhu in New Agents on the Horizon in Hepatocellular Carcinoma Therapeutic Advances in Medical Oncology, V 5(1), January 2013, 4150. Examples of compounds suitable for combination therapy where the host has or is at risk for HCC include anti-angiogenic agents, sunitinib, brivanib, linifanib, ramucirumab, bevacizumab, cediranib, pazopanib, TSU-68, lenvatinib, EGFR antibodies, mTOR inhibitors, MEK inhibitors, and histone decetylation inhibitors. EXAMPLES General methods The 19F and 31P spectra of the NXHMR were recorded on a 400 MHz Brücker Fourier transform spectrometer. Spectra were obtained from DMSO-dγ unless otherwise noted. Spin multiplicities are indicated by the symbols s (singlet), d (doblet), t (triplet), m (multiplet), and br (wide). Coupling constants (J) are reported in Hz. Reactions were generally carried out under a dry nitrogen atmosphere using anhydrous Sigma-Aldrich solvents. All common chemicals were purchased from commercial sources. zccAnn / zznz / E / YiAi The following abbreviations are used in the Examples: AUC: Area under the curve C24: Plasma drug concentration at 24 hours Cz+ss: Concentration at 24 hours after dosing at steady state Cmax: Maximum concentration of the drug reached in plasma DCM: Dichloromethane EtOAc: Ethyl acetate EtOH: Ethanol HPLC: High-performance liquid chromatography NaOH: Sodium hydroxide Na₂SO₄: Sodium sulfate (anhydrous) MeCN: Acetonitrile MeNHE: Methylamine MeOH: Methanol NazSCU: Sodium sulfate NaHCCh: Sodium bicarbonate NH4CI: Ammonium chloride NH4OH: Ammonium hydroxide PE: Petroleum ether PhaP: Triphenylphosphine HR: relative humidity Silica gel (230 to 400 mesh, sorbent) t-BuMgCl: f-Butyl magnesium chloride Tmax: Time at which Cmax is achieved THF: Tetrahydrofuran (THF), Anhydrous TP: Triphosphate zccAnn / zznz / E / YiAi EXAMPLE 1 Synthesis of compound 1 zccAnn / zznz / E / YiAi Chemical equation 2 Cl F Step 1: Synthesis of (2 / ?,37?,4 / ?,5 / ?)-5-(2-Amino-6-(methylamino')-9 / y-Dur¡n-9-¡l')-4fluoro-2-(hydroxymethyl')-4-methyltetrahydrofuran-3-ol (2-2) A 50 L flask was charged with methanol (30 L) and stirred at 10 ± 5°C. NH₂CH₃ (3.95 kg) was slowly vented into the reactor at 10 ± 5°C. Compound 2-1 (3.77 kg) was added in batches at 10 ± 5°C and stirred for 1 hour to obtain a clear solution. The reaction was stirred for an additional 6–8 hours, at which time HPLC indicated that the intermediate product was less than 0.1% of the solution. The reactor was charged with solid NaOH (254 g), stirred for 30 minutes, and concentrated at 50 ± 5°C (degree of vacuum -0.095). The resulting residue was charged with EtOH (40 L) and resuspended for 1 hour at 60°C. The mixture was then filtered through Celite and the filter cake was resuspended with EtOH (15 I) for 1 hour at 60°C. The filtrate was filtered once more, combined with the filtrate from the previous filtration, and then concentrated at 50 ± 5°C (vacuum: -0.095). A large amount of solid precipitated.EtOAc (6 I) was added to the solid residue and the mixture was concentrated at 50 ± 5°C (degree of vacuum: -0.095). DCM was then added to the residue and the mixture was resuspended under reflux for 1 hour, cooled to room temperature, filtered, and dried at 50 ± 5°C in a vacuum oven to provide compound 2-2 as a whitish solid (1.89 Kg, 95.3%, 99.2% purity). Analytical method for compound 2-2: The purity of compound 2-2 (15 mg) was determined using an Agilent 1100 HPLC system with a 4.6 x 150 mm Agilent Agoshent 120 ECC18 4-micron column under the following conditions: flow rate of 1 mL / min, read at 254 nm, column temperature of 30°C, injection volume of 15 mL, and run time of 31 minutes. The sample was dissolved in acetonitrile-water (20:80) (v / v). The gradient method is shown below. zccAnn / zznz / E / YiAi Time (min) A% (0.05 TFA in water) B% (Acetonitrile) 0 95 5 8 80 20 13 50 50 23 5 95 26 5 95 26.1 95 5 31 95 5 Step 2: Synthesis of ((5)-(((2 / ?,37?,4 / ?,5 / ?)-5-(2-Amino-6-(methylamino)-9 / 7t-purin-9-yl)-4fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-γ-isopropyl alaninate (Compound 1) Compound 2-2 and compound 2-3 (isopropyl((perfluorophenoxy)(phenoxy)phosphoryl)-lalaninate) were dissolved in THF (1 L) and stirred under nitrogen. The suspension was then cooled to below -5°C, and 1.7 M t-BuMgCl solution (384 mL) was slowly added over 1.5 hours while maintaining a temperature of 5-10°C. A solution of NH4Cl (2 L) and water (8 L) was added to the suspension at room temperature, followed by DCM. The mixture was stirred for 5 minutes before adding 5% aqueous K2CO3 solution (10 L), and the mixture was stirred for an additional 5 minutes before filtering through diatomaceous earth (500 g). The diatomaceous earth was washed with DCM, and the filtrate was separated. The organic phase was washed with a 5% aqueous K2CO3 solution (10 L x 2), brine (10 L x 3), and dried on NazSCk (500 g) for approximately 1 hour. This entire procedure was repeated 7 times in parallel, and the 8 batches were combined.The organic phases were filtered and concentrated at 45 ± 5°C (0.09 MPa vacuum). EtOAc was added, and the mixture was stirred for 1 hour at 60°C and then at room temperature for 18 hours. The mixture was then filtered and washed with EtOAc (2 L) to yield crude Compound 1. The crude material was dissolved in DCM (12 L), heptane (18 L) was added at 10–20°C, and the mixture was stirred for 30 minutes at this temperature. The mixture was filtered, washed with heptane (5 L), and dried at 50 ± 5°C to yield pure Compound 1 (1650 g, 60%). Analytical Method for Compound 1: The purity of Compound 1 (25 mg) was determined using an Agilent 1100 HPLC system with a Waters XTerra Phenyl 5pm 4.6 x 250 mm column under the following conditions: flow rate of 1 mL / min, read at 254 nm, column temperature of 30°C, injection volume of 15 mL, and run time of 25 minutes. The sample was dissolved in acetonitrile-water (50:50) (v / v). The gradient method is shown below. zccAnn / zznz / E / YiAi Time (min) A% (0.1% H3PO4 in water) B% (Acetonitrile) 0 90 10 20 20 80 20.1 90 10 25 90 10 EXAMPLE 2 Characterization of Compound 1 amorphous and crystalline Amorphous Compound 1 and Crystalline Compound 1 were initially analyzed by XRPD, 1HRMN, and HPLC. The XRPD patterns for both compounds are shown in Figure 1A, and the HPLC traces used to determine purity are shown in Figures 1B and 2A, respectively. Table 1 lists the XRPD peaks for Crystalline Compound 1, and Table 2 lists the relative retention times (RTTs) of the HPLC traces. Amorphous Compound 1 had a purity of 98.61%, and Crystalline Compound 1 had a purity of 99.11%. Both compounds were white solids. Figure 2B shows the TGA and DSC plots for Crystalline Compound 1. For Crystalline Compound 1, endothermy was observed at 88.6°C, and there was a 7.8% mass loss between 80 and 110°C. A sample of Compound 1 was recrystallized in EtOAc / hexane and extracted using ORTEP. The absolute structure of Compound 1 was confirmed by recrystallizing a single crystal. Figure 3 is the ORTEP drawing of Compound 1. Crystal data and measurement data are shown in Table 3. The absolute stereochemistry of Compound 1 based on X-ray crystallography is shown below: zccAnn / zznz / E / YiAi DSC data were collected on a TA Instruments Q2000 instrument equipped with a 50-position autosampler. Thermal capacity calibration was performed using sapphire, and energy and temperature calibration were performed using certified indium. Typically, approximately 3 mg of each sample, placed in a perforated aluminum tray, was heated at 10°C / min from 25°C to 200°C. A dry nitrogen purge of 50 mL / min was maintained over the sample. The instrument control software was Advantage for Q Series v2.8.0.394 and Thermal Advantage v5.5.3, and the data were analyzed using Universal Analysis v4.5A. TGA data were collected on a TA Instruments Q500 TGA, equipped with a 16-position autosampler. The instrument was temperature calibrated using certified Alumel and Nickel. Typically, 5–10 mg of each sample were loaded into a pre-weighed aluminum DSC tray and heated at 10°C / min from room temperature to 350°C. A nitrogen purge of 60 mL / min was maintained over the sample. The instrument control software was Advantage for Q Series v2.5.0.256 and Thermal Advantage v5.5.3, and the data were analyzed using Universal Analysis v4.5. Amorphous compound 1 (1-1): XH RMN (400 MHz, DMSO-ck} δ ppm 1.01 - 1.15 (m, 9 H), 1.21 (d, J^7.20 Hz, 3 H), 2.75 - 3.08 (m, 3 H), 3.71 - 3.87 (m, 1 H), 4.02 - 4.13 (m, 1 H), 4.22 - 4.53 (m, 3 H), 4.81 (s, 1 H), 5.69 - 5.86 (m, 1 H), 6.04 (br d, 7=19.33 Hz, 4 H), 7.12 - 7.27 (m, 3 H), l.TJ - 7.44 (m, 3 H), 7.81 (s, 1 H) Crystalline compound 1 (1-2): XH RMN (400 MHz, DMSO-d¿) δ ppm 0.97 - 1.16 (m, 16 H), 1.21 (d, 7=7.07 Hz, 3 H), 2.87 (br s, 3 H), 3.08 (s, 2 H), 3.79 (br d, 7=7.07 Hz, 1 H), 4.08 (br d, 7=7.58 Hz, 1 H), 4.17 - 4.55 (m, 3 H), 4.81 (quin, 7=6.25 Hz, 1 H), 5.78 (br s, 1 H), 5.91 - 6.15 (m, 4 H), 7.10 - 7.26 (m, 3 H), 7.26 - 7.44 (m, 3 H), 7.81 (s, 1 H) CUADRO 1 Lista de picos del Compuesto 1 cristalino Angle / °26 Spacing d / A Intensity / Counts Intensity / % 6.03 14.64 1005 39.0 7.36 12.00 315 12.2 7.94 11.13 1724 66.9 9.34 9.47 2500 97.0 9.51 9.29 860 33.4 9.77 9.05 1591 61.8 11.08 7.98 2576 100.0 12.02 7.36 171 6.6 12.95 6.83 319 12.4 13.98 6.33 241 9.4 14.30 6.19 550 21.4 14.69 6.03 328 12.7 15.20 5.82 2176 84.5 15.94 5.56 1446 56.1 16.75 5.29 1009 39.2 17.29 5.13 700 27.2 17.72 5.00 1213 47.1 18.11 4.89 1565 60.8 18.46 4.80 302 11.7 18.89 4.69 385 14.9 19.63 4.52 636 24.7 20.37 4.36 1214 47.1 20.74 4.28 1198 46.5 21.24 4.18 640 24.8 22.31 3.98 961 37.3 22.88 3.88 806 31.3 23.43 3.79 355 13.8 24.08 3.69 573 22.2 24.49 3.63 159 6.2 25.00 3.56 351 13.6 25.36 3.51 293 11.4 26.09 3.41 235 9.1 26.26 3.39 301 11.7 26.83 3.32 696 27.0 27.35 3.26 436 16.9 27.46 3.25 363 14.1 28.07 3.18 200 7.8 28.30 3.15 195 7.6 28.82 3.10 599 23.3 29.85 2.99 217 8.4 30.26 2.95 186 7.2 30.75 2.91 333 12.9 31.12 2.87 149 5.8 31.85 2.81 238 9.2 33.28 2.69 261 10.1 34.77 2.58 171 6.6 35.18 2.55 175 6.8 36.83 2.44 327 12.7 37.41 2.40 172 6.7 zccAnn / zznz / E / YiAi TABLE 2 Relative HPLC chromatography retention times of amorphous Compound 1 and the Crystalline compound 1 Amorphous Compound 1 Crystalline Compound 1 RRT % of area RRT % of area 0.48 0.15 0.48 0.17 0.51 0.04 0.48 0.17 0.48 0.15 0.94 0.12 0.51 0.04 1.00 99.11 0.94 0.13 1.04 0.22 0.98 0.21 1.37 0.07 1.00 98.61 1.04 0.29 1.37 0.31 TABLE 3 Crystal measurement v of Compound 1 data zccAnn / zznz / E / YiAi DC Link Accuracy = 0.0297A, Wavelength - 1.54184 Cell a=10.1884(3) b=28.6482(9) c= 12.9497(5) alpha=90 beta=113.184(4) gamma=90 Temperature 150K Calculated Reported Volume 3474.5(2) 3474.5(2) Space group P21 P 1 21 1 Hall group P 2yb P2yb Radical formula C24 H34 F N7 07 P 2(C24 H34 F N7 07 P) Sum formula C24 H34 F N7 07 P C48 H68 F2 N14 014 P2 Mr 582.55 1165.10 Dx, g cm'1 1.114 1.114 Z 4 2 Mu (mm1) 1.139 1.139 F000 1228.0 1228.0 F000' 1233.21 h, k, Imax 12,34,15 12,34,15 Nref 12742 [ 6510] 8259 Tmin, Tmax 0.790, 0.815 0.808, 1.000 Tmin' 0.716 Correction Method # of Reported Limits T: Tmin = 0.808 Tmax = 1.00 CorrAbs MULTI-SCAN Data Integrity 1.27 / 0.65 Theta (max) 68.244 R (reflections) 0.2091 ( 7995) wR2 (reflections) 0.5338 ( 8259) S 2.875 Npar 716 This initial characterization was followed by storage at 25°C / 60% relative humidity (RH) for 14 days with HPLC and XRPD analysis after 7 and 14 days. Figure 4A shows the XRPD results after 14 days at 25°C / 60% RH. The amorphous Compound 1 (sample 1-1) remained slightly crystalline, while the crystalline Compound 1 (sample 1-2) retained its crystallinity, but both compounds were stable after 14 days at 25°C / 60% RH. zccRnn / zznz / E / YiAi EXAMPLE 3 Formation of the oxalate salt compound 4 Initially, the oxalate salt of Compound 1, Compound 4, was formed by mixing the oxalic salt with solvent (5 vol, 100 ml) and allowing any solution to evaporate at room temperature. Any suspension was then matured (room temperature - 50°C) for 3 hours until crystallinity was achieved. Table 4 shows the different solvents used in the production of the compound. 4. All solvents except two (cyclohexane and n-heptane) produced crystalline products. Despite the high crystallinity and solubility of Compound 4, the oxalate salts are not acceptable for clinical development due to the potential for kidney stone formation, and other salts of Compound 1 were explored. TABLE 4 Formation of the Oxalate Compound 4 Solvent Observation after acid addition at room temperature Observation after maturation / evaporation EtOH OXA Solution - Form 1 IPA OXA Solution - Form 1 Acetone OXA Solution - Form 1 MEK OXA Solution - Form 1 EtOAc OXA Suspension - Form 1 / PrOAc OXA Suspension - Form 1 THF OXA Solution - Form 1 Toluene OXA Solution - Form 1 MeCN OXA Solution - Form 1 IPA: 10% water OXA Solution — Form 1 TBME OXA Suspension - Form 1 Cyclohexane Amorphous Suspension / Heptane Amorphous Suspension zccAnn / zznz / E / YiAi EXAMPLE 4 Salt compounds of Amorphous Compound 1 Since oxalate salt compound 4 (Example 3) could not be carried out in clinical trials due to its potential to form kidney stones, amorphous salts of Compound 1 were formed with the counterions listed in Table 5. Compound 1 was dissolved in tert-butanol (20 vol, 6 ml), and the solution was treated with the acid counterions (1 equivalent for each sample, except sample 1-9, which had 0.5 equivalents of sulfate). The samples were then frozen, with the solvent removed by lyophilization. The residual solid in samples 1-4, 1-5, 1-6, 1-7, 1-8, and 1-9 was initially analyzed by XRPD and HPLC. TABLE 5 Details of the formation of amorphous salt Sample ID Sample Details Stock Solution Details NMR Observation 1-4 HCl (1:1) THF 1M White solid 3 protons less ~0.3 eq f-BuOH 1-5 Sulfuric (1:1) THF 1M White solid 3 protons less ~0.3 eq f-BuOH 1-6 Fumaric (1:1) MeOH:THF (1:1) 0.5M Vitreous solid 1.05 eq fumaric acid 0.84 eq f-BuOH 1-7 Benzoic (1:1) THF 1M White solid 1.0 eq benzoic acid 0.34 eq f-BuOH 1-8 Succinic (1:1) MeOH 1M White solid ~1.1 eq succinic acid 0.37 eq f-BuOH 1-9 Sulfuric (0.5:1 acid:API) THF 1M White solid 3 protons less ~0.3 eq f-BuOH HRMN spectra were taken for all samples. Sample 1-4, HCl salt (1:1): Ή NMR (400 MHz, DMSO-d¿) δ ppm 0.93 - 1.39 (m, 16 H), 2.97 (br s, 2 H), 3.70 3.88 (m, 1 H), 4.10 (br s, 1 H), 4.18 - 4.49 (m, 3 H), 4.70 - 4.88 (m, 1 H), 5.71 - 5.94 (m, 1 H), 6.07 (br d, 7=19.07 Hz, 2 H), 7.14 - 7.27 (m, 3 H), 7.29 - 7.44 (m, 2 H), 7.83 - 8.19 (m, 1 H) Muestra 1-5, sal sulfúrica (1:1): Ή RMN (400 MHz, DMSO-ck) δ ppm 0.97 - 1.38 (m, 15 H), 2.96 (br s, 2 H), 4.06 4.18 (m, 1 H), 4.19 - 4.49 (m, 3 H), 4.66 - 4.91 (m, 1 H), 5.70 - 5.95 (m, 1 H), 5.96 - 6.16 (m, 2 H), 7.10 - 7.27 (m, 3 H), 7.30 - 7.43 (m, 2 H), 7.88 - 8.19 (m, 1 H) Muestra 1-6, sal fumárica (1:1): !H RMN (400 MHz, DMSO-ck) δ ppm 0.95 - 1.31 (m, 21 H), 2.87 (br s, 3 H), 3.79 (br d, 7=7.20 Hz, 1 H), 4.01 - 4.13 (m, 1 H), 4.16 - 4.23 (m, 1 H), 4.16 - 4.24 (m, 1 H), 4.20 (s, 1 H), 4.18 - 4.23 (m, 1 H), 4.24 - 4.52 (m, 1 H), 4.24 - 4.52 (m, 1 H), 4.24 - 4.49 (m, 1 H), 4.72 - 4.88 (m, 1 H), 5.68 - 5.86 (m, 1 H), 6.04 (br d, 7=19.33 Hz, 4 H), 6.63 (s, 1 H), 6.61 - 6.66 (m, 1 H), 7.12 7.27 (m, 3 H), 7.27 - 7.45 (m, 3 H), 7.81 (s, 1 H), 13.16 (br s, 2 H) Muestra 1-7, sal benzoica (1:1): !H RMN (400 MHz, DMSO-ck) δ ppm 0.96 - 1.30 (m, 15 H), 2.87 (br s, 3 H), 3.79 (br d, 7=7.07 Hz, 1 H), 4.07 (br s, 1 H), 4.20 (s, 1 H), 4.25 - 4.52 (m, 3 H), 4.81 (s, 1 H), 5.71 - 5.85 (m, 1 H), 6.04 (br d, 7=19.33 Hz, 4 H), 7.08 - 7.27 (m, 3 H), 7.27 - 7.43 (m, 3 H), 7.45 - 7.57 (m, 2 H), 7.63 (s, 1 H), 7.81 (s, 1 H), 7.95 (dd, 7=8.27, 1.33 Hz, 2 H), 12.98 (br s, 1 H) Muestra 1-8, sal succínica (1:1): RMN (400 MHz, DMSO-d¿) δ ppm 0.98 - 1.28 (m, 15 H), 2.42 (s, 5 H), 2.87 (br s, 3 H), 3.57 - 3.62 (m, 1 H), 3.70 - 3.86 (m, 1 H), 4.02 - 4.14 (m, 1 H), 4.20 (s, 1 H), 4.24 - 4.51 (m, 3 H), 4.70 - 4.88 (m, 1 H), 5.69 - 5.86 (m, 1 H), 6.04 (br d, 7=19.33 Hz, 4 H), 7.12 - 7.27 (m, 3 H), 7.27 - 7.44 (m, 3 H), 7.81 (s, 1 H), 11.95 - 12.58 (m, 2 H) Muestra 1-9, sal sulfúrica (0.5:1): RMN (400 MHz, DMSO-ck) δ ppm 1.02 - 1.31 (m, 15 H), 2.94 (br s, 3 H), 3.79 (br d, 7=7.20 Hz, 2 H), 4.09 (br s, 1 H), 4.22 - 4.48 (m, 3 H), 4.72 - 4.90 (m, 1 H), 5.71 - 5.92 (m, 1 H), 6.07 (br d, 7=19.07 Hz, 2 H), 7.12 - 7.28 (m, 3 H), 7.31 - 7.44 (m, 2 H), 7.75 - 8.19 (m, 1 H). The samples were then stored at 25°C / 60% relative humidity (RH) for 14 days, with HPLC and XRPD analysis performed after 7 (Figure 4B) and 14 days (Figure 5A). All prepared salts remained amorphous, and the observations are shown in Table 6. The monosulfate (sample 1-5) and succinate salts (sample 1-8) were found to be physically unstable and transformed into a gum during the course of the study. Both the fumarate (sample 1-6) and benzoate (sample 1-7) salts were found to be glassy solids. The HCl salt (sample 1-4) was found to retain its physical appearance. Surprisingly, the hemisulfate salt (sample 1-9) also retained its physical appearance as a white solid, in contrast to the monosulfate compound (sample 1-5), which was a sticky gum. The results are shown in Table 6.Monohydrochloride (HCl) salt (sample 1-4) and hemisulfate salt (sample 15-9) were found to be physically and chemically stable after 2 weeks of storage at 25°C / 60% relative humidity (RH). Although both salts remained stable over the two weeks, hemisulfate salt was superior to HCl salt because HCl salt was hygroscopic, making it less useful for long-term storage or use. TABLE 6 Stability of samples after 7 and 14 days at 25 °C / 60% RH zccRnn / zznz / E / YiAi Sample ID Exposure time at 25 °C / 60% RH (days) 0 7 14 HPLC Observation HPLC Observation HPLC Observation 1-1 98.6 White solid 98.7 White solid 98.5 White solid 1-2 99.1 White solid 99.2 White solid 99.0 White solid 1-3 99.7 White solid 99.6 White solid 99.4 White solid 1-4 98.7 White solid 98.8 White solid 98.6 White solid 1-5 98.4 White solid 55.7 White solid - Sticky gum 1-6 98.7 Vitreous solid 98.6 Clear glassy solid 98.4 Solid White glassy 1-7 98.8 White solid 98.8 Clear glassy solid 98.7 Clear glassy solid 1-8 98.7 Sticky white solid - Delicate / sticky oil - Delicate 1-9 98.7 White solid 98.1 White solid 96.4 White solid EXAMPLE 5 Characterization of the amorphous compound 2 Amorphous compound 2 was initially analyzed by XRPD, ^NMR, DSC, TGA and HPLC. The XRPD pattern for amorphous Compound 2 superimposed on amorphous and crystalline Compound 1 is shown in Figure 1A, and the XRPD pattern of amorphous Compound 2 alone is shown in Figure 5B. Table 7 lists the peaks of the XRPD pattern shown in Figure 5B. The HPLC trace for purity determination is shown in Figure 6A. Table 8 lists the relative retention times (RTTs) of the HPLC trace shown in Figure 6A. Amorphous Compound 2 had a purity of 99.68%. Figure 6B is a TGA and DSC plot of amorphous Compound 2. Experimental details of the TGA and DSC experiments are given in Example 2. zccAnn / zznz / E / YiAi TABLE 7 List of peaks for Amorphous Compound 2 Angle / °28 Spacing d / A Intensity / Counts Intensity / % 4.20 21.03 486 81.8 4.67 18.91 482 81.0 5.16 17.10 595 100.0 9.13 9.68 547 92.0 TABLE 8 HPLC chromatogram of amorphous compound 2 Amorphous Compound 2 RRT % area 0.48 0.02 0.48 0.02 0.67 0.01 0.94 0.13 1.00 99.68 1.04 0.06 Amorphous compound 2: *H NMR (400 MHz, DMSO-ck) δ ppm 0.93 - 1.29 (m, 13 H), 2.94 (br s, 3 H), 3.79 (td, 7=10.04, 7.07 Hz, 2 H), 4.05 - 4.19 (m, 1 H), 4.19 - 4.50 (m, 3 H), 4.81 (quin, 7=6.25 Hz, 1 H), 5.71 - 5.94 (m, 1 H), 5.97 - 6.16 (m, 2 H), 7.14 - 7.28 (m, 3 H), 7.31 - 7.44 (m, 2 H), 7.82 - 8.09 (m, 1 H) EXAMPLE 6 Crystallization of the amorphous compound 2 zccAnn / zznz / E / YiAi Since the hemisulfate salt was found to remain as a solid after the 14-day stability study, as shown in Table 6, preliminary tests were conducted to study the crystallization conditions with 11 different solvents. The amorphous compound 2 was suspended in 5 volumes of solvent at 25°C (samples 2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, 2-9, 2-10, and 2-11). For those samples that did not flow freely (2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, 2-8, and 2-10), an additional 5 volumes of solvent were added. The samples were then matured at 25–50°C (1°C / min between temperatures and 4 hours at each temperature) for 6 days, except for sample 2–1, which was observed to be a clear solution after 1 day and was allowed to evaporate under ambient conditions. The results are shown in Table 9.Crystalline patterns resulted from crystallization with isobutanol (sample 2-1), acetone (sample 2-2), EtOAc (sample 2-6), and iPrOAc (sample 2-7). Two poorly crystalline samples were also identified by crystallization with MEK (sample 2-4) and MIBK (sample 2-5). The XRPD patterns are shown in Figure 7A. TABLE 9 Crystallization conditions of Compound 2 Sample ID Solvent Observation after 5 volumes Observation after 10 volumes Observation after 1 day of maturation XRPD 2-1 IPA Solid - non-free-flowing Free-flowing suspension Solution, evaporated at room temperature giving a gum Gum 2-2 Isobutanol Solid - non-free-flowing Free-flowing suspension Suspension Crystalline Standard 2 2-3 Acetone Solid - non-free-flowing Free-flowing suspension Suspension Crystalline Standard 3 2-4 MEK Solid - non-free-flowing Free-flowing suspension Suspension Sparsely crystalline Standard 4 2-5 MIBK Solid - non-free-flowing Free-flowing suspension Suspension Sparsely crystalline Standard 4 2-6 EtOAc Solid - non-free-flowing Free-flowing suspension Suspension Crystalline Standard 1 2-7 ProOAc Solid - non-flowing Suspension of Suspension Crystalline - Free-flowing Pattern 1 2-8 THF Solid - not free-flowing Free-flowing suspension Sparsely crystalline 2-9 TBME Free-flowing suspension - Amorphous suspension 2-10 Toluene Solid - not free-flowing Free-flowing suspension Amorphous suspension 2-11 Heptane Free-flowing suspension - Amorphous suspension zccAnn / zznz / E / YiAi The seven samples (Samples 2-2, 2-3, 2-4, 2-5, 2-6, 2-7, and 2-8) were analyzed by DSC, TGA, 1H-NMR, and IC (Table 10, Figure 8A, Figure 8B, Figure 9A, Figure 9B, Figure 10A, Figure 10B, Figure 11A, and Figure 11B) as well as by X-ray diffraction after 6 days of storage at 25 °C / 60% relative humidity (RH) (all samples remained crystalline / poorly crystalline after stabilization). All samples retained approximately half the sulfate equivalent but contained a relatively large amount of residual solvent. A superposition of the X-ray diffractograms of the amorphous samples 2-9, 2-10, and 2-11 is shown in Figure 7B. TABLE 10 Characterization of samples of Crystalline Compound 2 Sample ID Solvent DSC TGA HR MN IC (Corrected for TGA) 2-2 Isobutanol Endo 113.8 °C 8.3% ambient 140 °C 1.1 eq isobutanol 0.45 eq 2-3 Acetone Endo 30-95 °C Endo 100-145 °C 7.6% ambient -140 °C 0.5 eq acetone 0.46 eq 2-4 MEK Endo broad complex 30-115 °C Endo 115-145 °C 8.5% ambient -140 °C 0.8 eq MEK 0.45 eq 2-5 MIBK Endo broad complex 30-105 °C Endo 114.7 °C 5.2% ambient -110 °C 0.2 eq MIBK 0.46 eq 2-6 EtOAc Acute Endo 113.6 °C 2.0% ambient - 100 °C 0.9 eq EtOAc 0.46 eq 2-7 ProOAc Endo 30-90 °C 1.6% ambient - 90 °C 0.8 eq ProOAc 0.45 eq 2-8 THF Endo 30-100 °C More acute Endo 115.6 °C 4.2% ambient - 130 °C 0.7 eq THF 0.45 eq NMR spectra were taken for all samples and are listed below. Sample 2-2: Ή RMN (400 MHz, DMSO-d¿) δ ppm 0.83 (d, 7=6.69 Hz, 7 H), 0.99 - 1.26 (m, 14 H), 1.61 (dt, 7=13.26, 6.63 Hz, 1 H), 3.73 - 3.87 (m, 2 H), 4.03 - 4.18 (m, 1 H), 4.18 - 4.51 (m, 4 H), 4.66 - 4.92 (m, 1 H), 4.70 - 4.90 (m, 1 H), 4.72 - 4.88 (m, 1 H), 5.81 (br s, 1 H), 5.93 - 6.11 (m, 2 H), 7.10 - 7.26 (m, 3 H), 7.14 - 7.26 (m, 1 H), 7.30 - 7.41 (m, 2 H), 7.94 (br s, 1 H) Muestra 2-3: XH RMN (400 MHz, DMSO-ck} δ ppm 1.00 - 1.26 (m, 13 H), 2.09 (s, 3 H), 3.74 - 3.87 (m, 2 H), 4.10 (br d, 7=7.70 Hz, 1 H), 4.22 - 4.50 (m, 3 H), 4.81 (quin, 7=6.28 Hz, 1 H), 5.71 - 5.90 (m, 1 H), 5.96 - 6.15 (m, 2 H), 7.12 - 7.26 (m, 3 H), 7.31 - 7.41 (m, 2 H), 7.79 - 8.07 (m, 1 H) Muestra 2-4: XH RMN (400 MHz, DMSO-d¿) δ ppm 0.91 (t, 7=7.33 Hz, 3 H), 1.01 - 1.28 (m, 13 H), 2.08 (s, 2 H), 3.72 - 3.89 (m, 2 H), 4.10 (br d, 7=8.08 Hz, 1 H), 4.23 - 4.47 (m, 3 H), 4.81 (quin, 7=6.25 Hz, 1 H), 5.69 - 5.89 (m, 1 H), 5.94 - 6.13 (m, 2 H), 7.14 - 7.25 (m, 3 H), 7.32 - 7.41 (m, 2 H), 7.79 - 8.11 (m, 1H) Muestra 2-5: XH RMN (400 MHz, DMSO-d¿) δ ppm 0.86 (d, 7=6.69 Hz, 1 H), 0.98 - 1.33 (m, 13 H), 2.02 - 2.09 (m, 1 H), 4.03 - 4.17 (m, 1 H), 4.22 - 4.50 (m, 3 H), 4.81 (quin, 7=6.25 Hz, 1 H), 5.81 (br s, 1 H), 5.93 6.15 (m, 2 H), 7.11 - 7.27 (m, 3 H), 7.31 - 7.41 (m, 2 H), 7.77 - 8.21 (m, 1 H) Muestra 2-6: XH RMN (400 MHz, DMSO-ck) δ ppm 0.98 - 1.28 (m, 15 H), 2.00 (s, 3 H), 3.99 - 4.14 (m, 3 H), 4.21 4.49 (m, 3 H), 4.81 (quin, 7=6.22 Hz, 1 H), 5.82 (br s, 1 H), 5.93 - 6.14 (m, 2 H), 7.11 - 7.26 (m, 3 H), 7.29 - 7.42 (m, 2 H), 7.79 - 8.17 (m, 1 H) Muestra 2-7: XH NMR (400 MHz, DMSO-d¿) δ ppm 0.92 - 1.28 (m, 17 H), 1.97 (s, 2 H), 4.04 - 4.16 (m, 1 H), 4.20 4.51 (m, 3 H), 4.71 - 4.93 (m, 2 H), 4.71 - 2.2 H (br). s, 1 H), 5.95 - 6.14 (m, 2 H), 7.11 - 7.28 (m, 3 H), 7.31 - 7.43 (m, 2 H), 7.75 - 8.21 (m, 1 H) Sample 2-8: !H NMR (400 MHz, DMSO-d¿) δ ppm 0.81 - 1.11 (m, 13 H), 1.19 (s, 1 H), 1.53 - 1.66 (m, 1 H), 3.87 4.01 (m, 1 H), 4.06 - 4.3 H (m, 4.3 H), 7=6.25 Hz, 1 H), 5.55 - 5.75 (m, 1 H), 5.77 - 5.97 (m, zccAnn / zznz / E / YiAi Η), 6.94 to 7.10 (m, 3 Η), 7.13 to 7.26 (m, 2 Η), 7.66 to 7.96 (m, 1 Η) EXAMPLE 7 Failure to crystallize the amorphous malonate salt (Compound 4) As shown in Example 3, a crystalline oxalate salt was identified by determining the appropriate salts for Compound 1, but the oxalate salt Compound 4 could not be carried out in clinical trials due to its potential to cause kidney stones. Therefore, crystallization of the chemically related malonate salt (Compound 5) was attempted using the same solvents as for the hemisulfate salt. Compound 1 (12 x 50 mg, samples 3-1, 3-2, 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10, 3-11, and 3-12) was dissolved in tert-butanol (20 vol), and the solutions were treated with 1 equivalent of a stock solution of malonic acid (1 M in THF). The samples were then frozen, with the solvent removed by lyophilization. For samples 3-1, 3-2, 3-3, 3-4, 3-5, 3-6, 3-7, 3-8, 3-9, 3-10 and 3-11, relevant solvent (5 volumes) was added at room temperature.All resulting solutions were allowed to evaporate under ambient conditions, while gums or solids were matured at 25–50°C (1°C / min between temperatures and 4 hours at each temperature) for 5 days. The solids were analyzed by XRPD (Figure 12B), but all samples were found to have formed a gum or to be amorphous (Figure 12B). The results are shown in Table 11. The only solid (amorphous) sample (3-12) was analyzed by Ψ-PMN and HPLC and found to contain approximately 1 equivalent of malonic acid (peak overlap), as well as 0.6 eq. t-BuOH. The compound was 99.2% pure (Figure 13A). Figure 12A is an XRDP of sample 3-12, and Figure 13A is the HPLC chromatography of sample 3-12. Sample 3-12: NMR (400 MHz, DMSO-ck) δ ppm 0.81 - 1.11 (m, 13 H), 1.19 (s, 1 H), 1.53 - 1.66 (m, 1 H), 3.87 - 4.01 (m, 1 H), 4.06 - 4.3 m (m, 1 H), 4.06 - 4.3 H (quin, 4.6 H). 7=6.25 Hz, 1 H), 5.55 - 5.75 (m, 1 H), 5.77 - 5.97 (m, 2 H), 6.94 - 7.10 (m, 3 H), 7.13 - 7.26 (m, 2 H), 7.66 - 7.96 (m, 7.9 H) zccAnn / zznz / E / YiAi TABLE 11 Crystallization Conditions of Amorphous Malonate Salt Compound 4 zccAnn / zznz / E / YiAi Sample ID Solvent Observation after 5 volumes Observation after 5 days of maturation / evaporation XRPD 3-1 IPA Clear solution* Clear gum - 3-2 Isobutanol Clear solution* Clear gum - 3-3 Acetone Clear solution* Clear gum - 3-4 MEK Clear solution* Clear gum - 3-5 MIBK Clear solution & gum Clear gum - 3-6 EtOAc Clear solution* Clear gum & crystal-like appearance Amorphous 3-7 ProOAc Gum Clear gum - 3-8 THF Clear solution* Clear gum - 3-9 TBME Thick suspension Clear gum - 3-10 Toluene White gum / solid White gum Amorphous 3-11 Heptane White solid (static) White gum Amorphous 3-12 - (White solid without solvent) (White sticky solid under ambient conditions) Amorphous *Evaporated at room temperature EXAMPLE 8 Failure to properly form salt using liquid-assisted milling (LAG) A liquid-assisted milling (LAG) study was conducted to determine appropriate salts other than hemisulfate using the 14 acid counterions in Table 12. TABLE 12 Counterion stock solutions used in LAG crystallization Counterion Solvent (1 M) Pamoic DMSO Malonic THF D-Glucuronic Water DL-Mandelic THF D-Gluconic THF Glycol ic THF L-Latic THF Oleic THF L-Ascorbic Water Adipic THF (heat) Caproic THF Stearic THF Palmitic THF Methanesulfonic THF zccAnn / zznz / E / YiAi Compound 1 (30 mg) was placed in HPLC vials with two 3 mm ball bearings. The materials were moistened with solvent (15 l of ethanol, samples 4-1, 4-2, 4-3, 4-4, 4-5, 4-6, 4-7, 4-8, 4-9, 4-10, 4-11, 4-12, 4-13, and 4-14) and 1 equivalence of the acid counterion was added. The samples were ground for 2 hours at 650 rpm using a Fritsch grinding system with an Automaxion adapter. Most of the samples after grinding were found to be transparent gums and were not analyzed further (Table 13). Those observed to contain solids were analyzed by XRPD and in all cases the patterns obtained were found to match those of the crystalline acid counterion without additional peaks (Figure 13B). TABLE 13 Observations and XRPD results of LAG from Compound 1 Sample ID Acid Observation after milling XRPD 4-1 Pamoic Yellow gum / solid Pamoic acid & amorphous halo 4-2 Malonic Clear gum - 4-3 D-Glucuronic White gum / solid D-Glucuronic acid & amorphous halo 4-4 DL-Mandelic Clear gum - 4-5 D-Gluconic Clear gum - 4-6 Glycolic Clear gum 4-7 L-Lactic Clear gum - 4-8 Oleic Clear gum - 4-9 L-Ascorbic White gum / solid L-Ascorbic acid & amorphous halo 4-10 Adipic Clear gum - 4-11 Caproic Clear gum - 4-12 Stearic White gum / solid Stearic acid & amorphous halo 4-13 Palmitic White gum / solid Acid palmitic & amorphous halo 4-4 Methanesulfonic Clear gum - EXAMPLE 9 Failure to obtain adequate salt formation with methyl ethyl ketone (MEK) Next, methyl ethyl ketone (MEK) was used as a solvent to study appropriate salts other than the hemisulfate salt. Using the 14 acidic counterions in Table 12, the study was conducted by dissolving Compound 1 (50 mg) in MEK (20 vol) at room temperature. The solutions were treated with 1 equivalent of the selected counterions (Table 12). The samples were then cooled to 5°C at 0.1°C / min and stirred at this temperature overnight. All samples were allowed to evaporate under ambient conditions, and the observed solids were analyzed by X-ray diffraction pair (XRPD). This evaporation yielded mainly gums, with the exception of the samples containing stearic acid (sample 4-12) and palmitic acid (sample 5-13), which provided glassy solvents. These solids were amorphous by XRPD, but no crystalline forms of the salt were obtained. The results are shown in Table 14. (Figure 13A). zccAnn / zznz / E / YiAi TABLE 14 Results of dissolving Compound 1 in MEK (20 volumes) Sample ID Acid Solvent for 1 M Acid Observation on Acid Addition Observation on Cooling Observation on Evaporation 5-1 Pamoic Acid DMSO Yellow Solution Yellow Solution Yellow Gum 5-2 Malonic Acid THF Solution Solution Clear Gum 5-3 D-Glucuronic Acid Water Solution Solution Clear Gum 5-4 DL-Mandelic Acid THF Solution Solution Clear Gum 5-5 D-Gluconic Acid THF White Precipitate Turbid Solution Clear Gum 5-6 Glycolic Acid THF Solution Solution Clear Gum 5-7 L-Lactic Acid THF Solution Solution Clear Gum 5-8 Oleic Acid THF Solution Solution Clear Gum 5-9 L-Ascorbic Acid Water Solution Solution Yellow Gum 5-10 Adipic Acid THF (heat) Solution Solution Clear Gum 5-11 Caproic Acid THF Solution Solution Clear Gum 5-12 Stearic Acid THF Solution Solution Turbid Solution Clear Glassy Solid* 5-13 Palmitic Acid THF Solution Clear glassy solid* 5-14 Methanesulfonic THF Solution Clear gum Stock solution prepared before acid addition * Samples were analyzed by XRPD and gave amorphous patterns plus acid counterion peaks Since all samples were amorphous, they were redissolved in MEK (5 vol) and cyclohexane (20 vol antisolvent) was added at room temperature, followed by 1 hour of stirring at 25°C. The samples were then matured between 50 and 5°C (1°C / min between temperatures, 4 hours at each temperature) for 2 days before the cycle was changed to 50–25°C for a further 4 days. The samples were visually inspected after maturation. The results are shown in Table 15. After maturation, all samples except 5-1 (containing pamoic acid) were found to be gums. Sample 5-1, a yellow solid, was analyzed by XRPD, and the pattern was found to match the known form of pamoic acid (Figure 14B); therefore, no crystalline forms of the salt were obtained. zccAnn / zznz / E / YiAi TABLE 15 Results of redissolution of Compound 1 in MEK (5 volumes) and antisolvent Sample ID Immediate Observation Observation after 10 minutes Observation after 60 minutes Observation after maturation 5-1 Precipitate Gum Gum Yellow suspension** 5-2 Precipitate Gum Gum Gum 5-3 Precipitate / Gum Gum Gum Gum 5-4 Precipitate Gum Gum Gum 5-5 Precipitate / Gum Gum Gum Gum 5-6 Precipitate Gum Gum Gum 5-7 Precipitate Gum Gum Gum 5-8 Precipitate Clear suspension Gum Gum 5-9 Precipitate Gum Gum Gum 5-10 Precipitate Gum Gum Gum 5-11 Precipitate Clear suspension Gum Gum 5-12 Precipitate Clear suspension Gum Gum 5-13 Precipitate Clear suspension Gum Gum 5-14 Precipitate Gum Gum Eraser **Sample analyzed by XRPD with known shape pattern of pamoic acid (no additional peaks) EXAMPLE 10 Failure to obtain a suitable salt formation using ethyl acetate Ethyl acetate was then used to study appropriate salts other than the hemisulfate salt. Using the 14 acid counterions in Table 12, the study was conducted by dissolving Compound 1 (50 mg) in ethyl acetate (20 vol) at 50°C. The solutions were treated with 1 equivalent of the selected counterions (Table 12). The samples were then cooled to 5°C at 0.1°C / min and stirred at this temperature for 4 days. The solutions were allowed to evaporate under ambient conditions, while the solids were analyzed by XRPD. The results of the ethyl acetate crystallizations are shown in Table 16. In contrast to Example 8, where MEK was the solvent, most of the samples were observed to be suspensions after cooling of the acid:compound mixture (those that were solutions were allowed to evaporate under ambient conditions).However, the XRPD diffractograms were found to generally match crystalline compound 1. Samples 6-2, 6-4, and 6-5 have some slight differences (Figure 14A and Figure 15A). No crystalline forms of the salt were obtained. TABLE 16 Results of dissolving Compound 1 in EtOAc (20 volumes) Sample ID Acid Solvent for 1 M Acid Observation on Acid Addition Observation on Cooling XRPD Observation on Evaporation 6-1 Pamoic Acid DMSO Yellow Solution Yellow Solution* - Gum 6-2 Malonic Acid THF Solution White Suspension Slight differences to free base - 6-3 D-Glucuronic Acid Water Solution Solution* - Gum 6-4 DL-Mandelic Acid THF Solution White Suspension Slight differences to free base - 6-5 D-Gluconic Acid THF White Precipitate Possible White Gum Slight differences to free base - 6-6 Glycolic Acid THF Solution White Suspension Free base - 6-7 L-Lactic Acid THF Solution White Suspension Free base - 6-8 Oleic Acid THF Solution White Suspension Free base - 6-9 L-Ascorbic Acid Water Solution Solution* White Solid on Side / Amorphous Yellow Gum 6-10 Adipic Acid THF (Heat) Solution White Suspension Free Base - 6-11 Caproic Acid THF Solution White Suspension Free Base - 6-12 Stearic Acid THF Solution White Suspension Free Base - 6-13 Mythic Palm THF SolutionWhite suspension Free base - 6,14 Methanesulfonic acid THF White precipitate Clear solution / gum* - Clear gum EXAMPLE 11 Determination of Chemical Purity by HPLC The purity analysis in Example 2 and Example 4 was performed on an Agilent HP1100 Series system equipped with a diode array detector and using ChemStation vB.04.03 software using the method shown in Table 17. zccAnn / zznz / E / YiAi TABLE 17 HPLC method for chemical purity determinations Parameter Value Method Type Reversed phase with gradient elution Sample preparation 0.5 mg / ml in acetonitrile : water 1:1 Column Supelco Ascentis Express C18, 100 x 4.6 mm, 2.7 pm Column temperature (°C) 25 Injection ( 1) 5 Wavelength, width 255, 90 Flow rate = (ml / min) 2 Phase A 0.1% TFA in water Phase B 0.085% TFA in acetonitrile Schedule Time (minutes) % of Phase A % of Phase B 0 95 5 6 5 95 6.2 95 5 8 95 5 EXAMPLE 12 Powder X-ray diffraction (XRPD) techniques The XRPD patterns in Examples 2, 3, 4, 5, 6, 7, 8, and 9 were collected on a PANalytical Empyrean diffractometer using K-Cu radiation (45 kV, 40 mA) in transmission geometry. A 0.5° slit, a 4 mm mask, and 0.4 rad Soller slits with a focusing mirror were used in the incident beam. A PIXcel3D detector, placed in the diffracted beam, was equipped with a receiving slit and 0.04 rad Soller slits. Instrument performance was verified weekly using silicon powder. The software used for data collection was X'Pert Data Collector v. 5.3, and the data were analyzed and presented using Diffract Plus EVA v. 15.0.0.0 or Highscore Plus v. 4.5. Samples were prepared and analyzed on a metal well plate or Millipore 96 in transmission mode. A transparent X-ray film was used between the metal foils on the metal well plate, and powders (approximately 12 mg) were used as received. The Millipore plate was used to isolate and analyze solids from suspensions by adding a small amount of suspension directly to the plate before filtration under a slight vacuum. The scan mode for the metal plate used the gonium scan axis, while a 20° scan was used for the Millipore plate. A performance verification was performed using silicon powder (metal well plate). Data collection details included an angular range of 2.5 to 32.0°, a step size of 0.0130°, and a total collection time of 2.07 minutes. Samples were also collected using a Bruker D8 diffractometer with Cu K- radiation (40 kV, 40 mA), a Θ-20 goniometer, V4 divergence and receiving slits, a Ge monochromator, and a Lynxeye detector. Instrument performance was verified using a certified corundum standard (NIST 1976). The software used for data collection was DiffracPlus XRD Commander v2.6.1, and the data were analyzed and presented using DiffracPlus EVA vl5.0.0.0. The samples were processed under ambient conditions as flat-plate samples using powder as received. The sample was gently packed into a cavity cut into a bottom-zero polished silicon wafer (510). The sample was rotated in its own plane during analysis. Data collection details included an angular range of 2 to 42° 20', a step size of 0.05° 20', and a collection time of 0.5 s / step. zccAnn / zznz / E / YiAi EXAMPLE 13 Synthesis of amorphous compound 2 A 250 ml flask was filled with MeOH (151 ml) and the solution was cooled to 0–5°C. Concentrated H₂SO₄ solution was added dropwise over 10 minutes. A separate flask was filled with Compound 1 (151 g) and acetone (910 ml), and the solution was added dropwise. HzSCM / MeOH at 25-30°C for 2.5 hours. A large amount of solid precipitated. After stirring the solution for 12-15 hours at 25-30°C, the mixture was filtered, washed with MeOH / acetone (25 ml / 150 ml) and dried at 55-60°C under vacuum to provide Compound 2 (121 g, 74%). Analytical Method for Compound 2: The purity of Compound 2 was determined using an Agilent 1100 HPLC system with a Waters XTerra Phenyl 5μAti 4.6*250 mm column under the following conditions: flow rate of 1 mL / min, read at 254 nm, column temperature of 30°C, injection volume of 10 mL, and run time of 30 minutes. The sample was dissolved in ACN:water (90:10, v / v). The gradient method for separation is shown below. The Rt (min) of Compound 2 was approximately 12.0 minutes. zccAnn / zznz / E / YiAi Time (min) 0.1% H3PO4 in water (A)% Acetonitrile (B)% 0 90 10 20 20 80 20.1 90 10 30 90 10 ^NMR: (400 MHz, DMSO-ra): δ 8.41 (br, 1H), 7.97 (s, 1H), 7.36 (t, J= 8.0 Hz, 2H), 7.22 (d, 7 = 8.0 Hz, 2H), 7.17 (t, 7 = 8.0 Hz, 1H), 6.73 (s, 2H), 6.07 (d, 7= 8.0 Hz, 1H), 6.00 (dd, 7 = 12.0, 8.0 Hz, 1H), 5.81(br, 1H), 4.84-4.73 (m, 1H), 4.44-4.28 (m, 3H), 4.10 (t, 7= 8.0 Hz, 2H), 3.85-3.74 (m, 1H), 2.95 (s, 3H), 1.21 (s, 7= 4.0 Hz, 3H), 1.15-1.10 (m, 9H). EXAMPLE 14 Characterization of Compound 2 Compound 2 was further characterized by spectroscopy, δNMR, 13CNMR, 19FNMR, MS, HPLC, and XRPD (Figure 15B). Residual solvent was measured by GC. Water content was measured by Karl Fischer titration, and was found to be only 0.70%. The data are summarized in Table 18. TABLE 18 Summary of additional characterization data for Compound 2 Test Result Appearance White solid NMR 'HRMN' peaks are listed in example 4 EM EM(ESI+ve) (M+H]+ = 582.3 - fits structure HPLC 99.8% by AUC at 254 nm (average of two preparations) Residual solvent by GC Methanol - 57 ppm Acetone - 752 ppm Dichloromethane - 50 ppm Ethyl acetate - 176 ppm Water content 0.70% zccRnn / zznz / E / YiAi EXAMPLE 15 Solubility of Compound 1 vs. Solubility of Compound 2 Compound 1 and Compound 2 were tested for solubility in biorelevant test media, including simulated gastric fluid (SGF), simulated fasting gastric fluid (FaSSIF), and simulated feeding gastric fluid (FeSSIF). Results for Compound 1 are shown in Table 19, and results for Compound 2 are shown in Table 20. Samples were stirred at room temperature (20–25°C). Compound 2 was more than 40 times more soluble than Compound 1 in water at 2 hours and more than 25 times more soluble at 24 hours. Under SGF conditions, Compound 2 had a solubility of 84.2 mg / mL at 24 hours compared to a solubility of 15.6 mg / mL for Compound 1 at the same time point.Compound 2 was also more soluble at 2 hours under SGF conditions than Compound 1, and soluble enough to allow testing even after 48 hours, whereas testing at 48 hours was not performed with Compound 1. TABLE 19 Results of the solubility test of Compound 1 Test Media Solubility (in mg / ml) Appearance Descriptive Term 2 hours 24 hours Water 1.5 2.5 Clear solution* Slightly soluble SGF 13.8 15.6 Clear solution with gum at the bottom Slightly soluble FaSSIF 1.7 1.7 Cloudy Slightly soluble FeSSIF 2.8 2.9 Cloudy Slightly soluble The sample appeared clear, but a solubility of only 1.5 mg / ml was achieved. Upon further investigation, a gummy film was observed to form on the stirring rod. The active pharmaceutical ingredient of compound 1 formed a gummy ball in diluent (90% water / 10% acetonitrile) during standard preparation, which required a long sonication time to dissolve completely. TABLE 20 Results of the solubility test of Compound 2 zccAnn / zznz / E / YiAi Test Media Solubility (in mg / ml of salt base) Appearance Descriptive term 2 hours 24 hours 48 hours Water 65.3 68.0 N / A Cloudy Soluble SGF 89.0 84.2 81.3 Cloudy Soluble FaSSIF 1.9 2.0 N / A Cloudy Slightly soluble FeSSIF 3.3 3.4 N / A Cloudy Slightly soluble EXAMPLE 16 Chemical stability of Compound 2 Compound 2 was tested for chemical stability at 25 and 40°C over a 6-month period, monitoring organic purity, water content, HRMN, DSC, and Raman IR. The container closure system for the study consisted of a medicinal valve bag with a pharmaceutical film laminated over the bag and desiccant silica gel between the two layers. One gram of Compound 2 was measured into each container. The bags were stored at 25°C / 60% RH and 40°C / 75% RH. Organic purity, water content, HRMN, DSC, and Raman IR were measured at Time 0, Month 1, Month 2, Month 3, and Month 6. The purity of Compound 2 was obtained using a Shimadzu LC-20AD system with a Waters XTerra Phenyl column, 4 pm, 4.6 x 250 mm, under the following conditions: flow rate of 1 mL / min, read at 254 nm, column temperature of 35°C, and injection volume of 10 pl. The sample was dissolved in acetonitrile-water (90:10) (v / v). The gradient method is shown below. Time (min) A° / o (ACN) B% (water) 0 90 10 20 20 80 20.1 90 10 30 90 10 The water content of Compound 2 (250 mg) was determined by a water titration apparatus using the Karl Fischer titration method. The results are shown in Table 21 and Table 22. When Compound 2 was stored for 6 months at 25 and 40°C, the degradation rate was minimal. At 3 months, Compound 2 had a purity of 99.75% at 25°C and 99.58% at 40°C. At 6 months, Compound 2 still had a purity of 99.74% at 25°C and 99.30% at 40°C. At 25°C, the percentage of degradation product increased from 0.03% on day 0 to 0.08% after 6 months. At 40°C, the percentage of degradation product increased from 0.03% to 0.39%. Over the course of 6 months, the percentage of water increased by approximately 0.6% at 25°C and increased by approximately 0.7% at 40°C. The characterization by ^NMR, Raman and DSC of Compound 2 at 1, 2, 3 and 6 months was the same as the characterization of Compound 2 on day 0 under both temperature conditions (Table 22), highlighting the long-term stability of Compound 2. zccAnn / zznz / E / YiAi TABLE 21 Degradation rate of Compound 2 for more than 6 months at 25 and 40°C Time tested Percentage of water Percentage of purity Percentage of degradation product Percentage of maximum impurity 25 °C Day 0 1.2 99.82 0.03 0.12 Month 1 1.9 99.77 0.04 0.12 Month 2 1.8 99.75 0.06 0.12 Month 3 1.8 99.75 0.06 0.12 Month 6 1.8 99.74 0.08 0.13 40 °C Day 0 1.2 99.82 0.03 0.12 Month 1 2.0 99.71 0.09 0.12 Month 2 1.9 99.63 0.15 0.12 Month 3 1.9 99.58 0.20 0.12 Month 6 1.9 99.30 0.39 0.14 TABLE 22 Characterization of Compound 2 during the degradation study Time tested 1HRMN Raman DSC 25 °C Day 0 Initial test Initial test Initial test Month 1 Same as day 0 Same as day 0 Same as day 0 Month 2 Same as day 0 Same as day 0 Same as day 0 Month 3 Same as day 0 Same as day 0 Same as day 0 Month 6 Same as day 0 Same as day 0 Same as day 0 40 °C Day 0 Initial test Initial test Initial test Month 1 Same as day 0 Same as day 0 Same as day 0 Month 2 Same as day 0 Same as day 0 Same as day 0 Month 3 Same as day 0 Same as day 0 Same as day 0 Month 6 Same as day 0 Same as day 0 Same as day 0 zccAnn / zznz / E / YiAi Additional chemical stability studies of Compound 2 were conducted to determine impurity and water levels. Three conditions were tested: accelerated stability (40 ± 2°C / 75 ± 5% RH) for 6 months, ambient stability (25 ± 2°C / 60 ± 5% RH) for 9 months, and stability under refrigeration (5 ± 3°C) for 9 months. The results for accelerated stability, ambient stability, and refrigeration are shown in Tables 23, 24, and 25, respectively. Based on the results of these studies, Compound 2 is very chemically stable. In the accelerated stability study (Table 23), at each time point (first 10 months, third month, and sixth month) when Compound 2 was measured, Compound 2 always appeared as a white solid, and its IR value matched the reference standard. After 6 months, the total impurities of related Substance 1 were 0.08%, and no related Substance 2 or isomers were detected. TABLE 23 Accelerated stability (40 + 2°C / 75 + 5% RH) of Compound 2 Specified Elements n Test Time Point 0 month 1st month 3rd month 6th month Appearance White or off-white solid White solid White solid White solid White solid IR corresponds to reference standard corresponds to reference standard / corresponds to reference standard corresponds to reference standard Water <2.0% 0.45% 0.21% 0.36% 0.41% Related Substance 1 Impurity A <0.15% N / A Impurity B <0.15% N / A Impurity F <0.15% N / A 0.01% Impurity H <0.15% N / A Any other individual impurity <0.10% 0.01% 0.02% 0.01% 0.05% Total Impurities <0.2% 0.01% 0.02% 0.02% 0.08% Substance Impurity G <0.15% NDNDNDND related to 2 Isomer Impurity C <0.15% ND / NDND Impurity D <0.15% ND / NDND Impurity E <0.15% ND / NDND Assay 98.0%~102.0 % 98.8% 101.5 % 99.6% 99.5% TAMC microbial test <1000 cfu / q <1 cfu / q / / / Mold and yeast <100 cfu / g <1 cfu / g / / / E.coli Not detected ND / / / ND: Not detected In the ambient stability study, where appearance, IR, water, and impurity levels were measured over nine months, Compound 2 consistently appeared as a white solid, and its IR values ​​always matched those of the reference sample. The results (Table 24) highlight the chemical stability of Compound 2. After nine months, the water content in the sample was only 0.20%, and the total impurities from Related Substance 1 were only 0.02%. As in the accelerated stability studies, Related Substance 2 and any isomers of Compound 2 were not detected. TABLE 24 Ambient stability (25 + 2°C / 60 + 5% RH) of Compound 2 Element Specification Test Time Point 0 month 1st month 3rd month 6th month 9th month Appearance White or off-white solid White solid White solid White solid White solid Off-white solid IR corresponds to reference standard corresponds to reference standard / corresponds to reference standard corresponds to reference standard corresponds to reference standard Water <2.0% 0.45% 0.19% 0.29% 0.46% 0.20% Related Standard 1 Impurity A <0.15% NDNDNDNDND Impurity B <0.15% NDND 0.03% NDND Impurity F <0.15% NDND 0.02% 0.01% ND Impurity H <0.15% NDNDNDNDND Any other <0.10% 0.01% 0.01% 0.03% 0.02% 0.02% Individual Impurity Total Impurities <0.2% 0.01% 0.02% 0.11% 0.05% 0.02% Related Substance 2 Impurity G <0.15% NDNDNDNDND Isomer 0 Impurity C <0.15% ND / NDNDND Impurity D <0.15% ND / NDNDND Impurity E <0.15% ND / NDNDND Assay 98.0%~102.0 % 98.8% 101.1% 99.6% 99.7% 100.9% Microbial Test TAMC < 1000 cfu / g <1 cfu / g / / / / Mold and Yeast < 100 cfu / g <1 cfu / g / / / / E. coli Not Detected ND / / / / ND: Not detected The results of the stability measurement under refrigerator conditions are shown in Table 25. The only impurities detected even after 9 months were those of related substance 1 and water. The water content after 9 months was 0.32%, and the total impurities of related substance 1 were only 0.01% of the sample. Compound 2 is very chemically stable under refrigerator conditions. TABLE 25. Stability under refrigerator conditions (5 + 3°C of Compound 2 Element Specification Test Time Point 0 month 1st month 3rd month 6th month 9th month Appearance White or off-white solid White solid White solid White solid White solid Off-white solid IR corresponds to reference standard corresponds to reference standard / corresponds to reference standard corresponds to reference standard Corresponds to reference standard Water <2.0% 0.45% 0.19% 0.32% 0.42% 0.32% Related Substance 1 Impurity A <0.15% NDNDNDNDND Impurity B <0.15% NDND 0.01% NDND Impurity at F <0.15% NDNDNDNDND Impurity at H <0.15% NDNDNDNDND Any other individual impurity 1 <0.10% 0.01% 0.01% 0.01% 0.01% 0.01% Total Impurities <0.2% 0.01% 0.01% 0.03% 0.03% 0.01% Related Substance 2 Impurity at G <0.15% NDNDNDNDND Isomer 0 Impurity at C <0.15% ND / NDNDND Impurity at D <0.15% ND / NDNDND Impurity at E <0.15% ND / NDNDND Assay 98.0%~ 102.0 % 98.8% 101.1 % 100.2% 98.6% 101.4% Microbial test TAMC <1000 CFU / g <1 CFU / g / / / / Mold and yeast <100 CFU / g <1 CFU / g / / / / E. coli Not detected ND / / / / ND: Not detected EXAMPLE 17 Plasma levels of metabolites after single oral doses of Compound 2 A single oral dose of Compound 2 was administered to rats, dogs, and monkeys, and plasma levels of certain metabolites shown in Chemical Equation 1 were measured. The conversion of Compound 2 into Compound 1 and metabolite 1-7 is shown in Table 26, and the results for metabolite 1-8 and metabolite 1-2 are shown in Table 27. In rats, low levels of Compound 1 exposure were observed, but high levels of metabolite 1-7, the active triphosphate nucleoside metabolite (metabolite 1-6), were observed. In monkeys, exposures to Compound 1 were approximately dose-proportional. In dogs, supra-dose-proportional exposures to Compound 1 were measured, indicative of first-pass metabolic clearance in the liver. Throughout the study, significantly more vomiting was observed in dogs (5 / 5 in the high-dose group) than in monkeys (1 / 5 in the high-dose group). TABLE 26 Plasma levels of Compound 1 and metabolite 1-7 after single oral doses of Compound 2 zccAnn / zznz / E / YiAi Species Dose* (mg / kg) Compound 1 Metabolite 1-7 Cmax (nq / ml) Tmax (hr) AUCo-ultimate (hr*nq / ml) Cmax (nq / ml) AUCo-ultimate (hr*nq / ml) Rata 500 70.5 0.25 60.9 748 12000 Dogb 30 1530 0.25-1 1300 783 9270 100 8120 0.5-1 10200 2030 24200 300 21300 204 44300 4260 60800 Monob 30 63.5 0.5-2 176 42.5 1620 100 783 1-2 1100 131 3030 300 501 204 1600 93.6 3660 males per dose per species; * dose formulations: a0.5% CMC, 0.5% Tween 80 in water; bpowder in capsules TABLE 27 Plasma levels of metabolites 1-8 and 1-2 after a single oral dose of Compound 2 Species Dose* (mg / kg) Metabolite 1-8 Metabolite 1-2 Cmax (ng / ml) AUCo-last (hr*ng / ml) Cmax (ng / ml) AUCo-last (hr*ng / ml) Ratea 500 5060 35100 9650 20300 Dog 30 291 905 196 610 100 1230 4370 886 2830 300 5380 35300 2380 8710 Monob 30 209 5690 300 1730 100 406 12300 1350 8160 300 518 16800 1420 11400 males per dose per species; *dose formulations: a0.5% CMC, 0.5% Tween 80 in water; bpowder in capsules. EXAMPLE 18 Tissue exposure to active triphosphate following oral dosing of Compound 2 Liver and heart tissue levels of active triphosphate (TP) from Compound 1 (metabolite 1-6) were measured 4 hours after oral doses of Compound 2. Liver and heart samples were obtained 4 hours after a single dose of Compound 2, flash-frozen, homogenized, and analyzed by LC-MS / MS to determine intracellular levels of active TP. Tissue levels were measured in rats, dogs, and monkeys, as shown in Figure 16A. High levels of active TP were measured in the livers of all species analyzed. Relatively low levels of active TP were measured in dog hearts due to saturation of first-pass hepatic metabolism, and non-quantifiable levels of TP were measured in rat and monkey hearts, indicating liver-specific formation of active TP. Although not shown, compared to the Compound 1 dose, the Compound 2 dose improved TP distribution. EXAMPLE 19 Pharmacological comparison of Compound 1 vs Compound 2 in dogs A direct comparison was made of dogs administered Compound 1 and Compound 2. The study measured plasma levels of Compound 1 and metabolite 1-7 (from Chemical Equation 1) up to 4 hours after dosing with Compound 1 (25 mg / kg) and Compound 2 (30 mg / kg) (Table 28), and the AUC(0-4hr) of metabolite 1-7 was twice as large with Compound 2 compared to Compound 1. Dose-normalized exposures to Compound 1 and metabolite 1-7 are shown in Table 28. AUC(0-4h) values ​​for Compound 1, metabolite 1-7, and the sum of Compound 1 + metabolite 1-7 were higher after dosing with Compound 2. TABLE 28 Comparison of plasma levels after dosing with Compound 1 vs Compound 2 zccAnn / zznz / E / YiAi Compound dosage AUC(0-4hr)a (pM*hr) with normalized mean dose for: Compound 1 Metabolite 1-7 Compound 1 + Metabolite 1-7 Compound 1 (25 mq / kq) 0.2 1.9 2.1 Compound 2 (30 mq / kq) 1.0 4.1 5.1 ¡AUC(o-4hr) normalized values ​​at a dose of 25 mg / kg Triphosphate concentrations in the liver / heart ratio indicate that dosing with Compound 2, compared to Compound 1, increases the selective delivery of triphosphate to the liver, as shown in Table 29. The AUC(0-4 h) of the active guanine metabolite (1-6) after administration of Compound 1, measured in the heart, was 174 pM*hr, while the AUC(0-4 h) of the active guanine metabolite (1-6) after administration of Compound 2, measured in the heart, was 28 pM*hr. The liver / heart ratio for Compound 2 was 20 compared to a liver / heart ratio of 3.1 for Compound 1. zccAnn / zznz / E / YiAi TABLE 29 Comparison of liver vs. heart exposure after dosing with Compound 1 and Compound 2 Compound dosage AUC(o-4hr)a (pM*hr) with normalized mean dose for: Liver Heart Liver / heart Compound 2 565 28b 20 Compound 1 537 174 3.1 Active TP concentrations (1-6; Chemical Equation 1) normalized to a dose of 25 mg / kg Extrapolated below the lower limit of quantification of the calibration curve The effect of greater liver selectivity over heart selectivity when Compound 2 was administered compared to Compound 1 is also shown in Figure 16B. Heart and liver tissue levels of active triphosphate after a dose of Compound 2 (30 mg / kg) were compared to tissue levels of active triphosphate after a dose of Compound 1 (25 mg / kg). Active TP concentration was higher in the liver than in the heart for both Compound 1 and Compound 2, but active TP was more selective for the liver over the heart when Compound 2 was administered compared to Compound 1. EXAMPLE 20 Plasma profiles of Compound 2 metabolites in rats vs monkeys Male Sprague-Dawley rats and cynomolgus monkeys (3 animals per dose group) received single oral doses of Compound 2. Plasma aliquots prepared from dichlorvos-treated blood samples were analyzed by LC-MS / MS to determine the concentrations of Compound 1 and metabolite 1-7 (the active triphosphate nucleoside metabolite of Compound 2 shown in Chemical Equation 1), and pharmacokinetic parameters were determined using WinNonlin. Results for a single 500 mg / kg dose in rats are shown in Figure 17, and results for single 30, 100, or 300 mg / kg doses in monkeys are shown in Figure 18. Results are also summarized in Table 30. High plasma levels of metabolite 1-7, the active triphosphate (TP) nucleoside metabolite of Compound 2, are indicative of high TP formation, even in rats where very low plasma levels of the parental nucleotide prodrug are observed due to the short half-life of Compound 1 in rat blood (<2 min). Persistent plasma levels of metabolite 1-7 reflect the long half-life of TP. In monkeys, plasma exposures (AUC) of Compound 1 were approximately dose-proportional, while exposures to metabolite 1-7 were somewhat less than dose-proportional, although AUC values ​​for the parent drug and the active TP nucleoside metabolite continue to increase at the highest dose tested (300 mg / kg). Oral administration of Compound 2 in rats and monkeys resulted in high, dose-dependent plasma exposures to metabolite 1-7 (the intracellular active triphosphate nucleoside metabolite of Compound 2); exposure to metabolite 1-7 continued to increase up to the highest dose tested, reflecting substantial formation of the active TP in these species. zccAnn / zznz / E / YiAi TABLE 30 Plasma levels of Compounds 1 v 1-7 after a single oral dose of Compound 2 Species Rataa Monob Dose (mg / kg) 500 30 100 300 Compound 1 Cmax(ng / ml) 60.8 63.5 783 501 Tmax (hr) 0.25 0.5-2 1-2 204 AUCo-ú Itima (hr* ng / ml) 78.2 176 1100 1600 Metabolite 1-7 Cmax (ng / ml) 541 42.5 131 93.6 AUCo-ú Itima (hr* ng / ml) 9640 1620 3030 3660 Tmax (hr) 6-8 12-24 4 4-24 Ti / 2 (hr) 15.3 11.5 15.0 18.8 Dosage formulations: a0.5% CMC, 0.5% Tween 80 in water; bpowder in capsules EXAMPLE 21 Effect of the active triphosphate of Compound 1 vs. Compound 2 on mitochondrial integrity The relative efficiency of incorporation of the active triphosphate (TP) of Compound 1 and Compound 2, metabolite 1-6 (Chemical Equation 1), by human mitochondrial RNA polymerase was compared with the relative efficiency of the active TP of sofosbuvir and the active TP of INX-189. Compound 1 and Compound 2 are unlikely to affect mitochondrial integrity, as their active triphosphate is poorly incorporated by human mitochondrial RNA polymerase with an efficiency similar to that of the triphosphate of sofosbuvir; the relative incorporation efficiency of the triphosphate of INX-189 was up to 55-fold higher. The results are shown in Table 31. The incorporation of these analogs by human mitochondrial RNA-dependent RNA polymerase (POLRMT) was determined according to Arnold et al. (Sensitivity of Mitochondrial Transcription and Resistance of RNA Polymerase II Dependent Nuclear Transcription to Antiviral Ribonucleotides. PLoS Pathog., 2012, 8, el003030). TABLE 31 Kinetic parameters for nucleotide analogues evaluated with human mitochondrial zccAnn / zznz / E / YiAi RNA polymerase Nucleotide analogue Kpol (s1) Kd,app (|JM) KrοI / Kdfapp (|JM Relative efficiency* UTP of 2 deoxy-2'-F-2'C-methyl (active TP of sofosbuvir) 0.00034 ± 0.00005 590 ± 250 5.8 x 10'7 + 2.6 x 10'7 1.0 x10'6 GTP of 2'-C-methyl (active TP of INX189) 0.051 + 0.002 240 ± 26 2.1 x 10~4 + 0.2 x 10 4 5.5 x10'5 Active TP of Compound 1 and Compound 2 (metabolite 1-6) 0.0017 ± 0.0002 204 ± 94 8.3 x 10'6± 4.0 x ΙΟ'6 2.2 xlO'6 *Relative efficiency — (Kpol / Kd,app) nucleotide analogue / (Kpol / Kd,app) natural nucleotide EXAMPLE 22 Compound 1 activity against replicons containing the NS5B sequence A panel of replicates containing NS5B sequences from several HCV genotypes derived from 6 laboratory reference strains (GTla, Ib, 2a, 3a, 4a and 5a) (Figure 19) and from 8 plasma samples from HCV patients (GTla, Ib, 2a, 2b, 3a-l, 3a-2, 4a and 4d) (Figure 20) were used to determine the potency of Compound 1 and sofosbuvir. Compound 1 was more potent than sofosbuvir against both clinical and laboratory HCV strains. Compound 1 exhibited potent pan-genotypic antiviral activity in vitro against wild-type clinical isolates with EC95 <80 nM, which is 4 to 14 times more potent than sofosbuvir. As shown in Figure 20, EC95 values ​​for Compound 1 were 7 to 33 times lower than sofosbuvir against clinical isolates of all HCV genotypes tested. EC95 values ​​for Compound 1 were 6 to 11 times lower than sofosbuvir against laboratory strains of HCV Genotypes 1 to 5 (Figure 19). EXAMPLE 23 Single ascending dose study (SAP) of Compound 2 in healthy volunteers (Part A) vs GT1-HCV infected patients (Part B) Compound 2 was tested in a single ascending dose (SAD) study to assess its safety, tolerability, and pharmacokinetics in healthy subjects (Part A). Part A was a randomized, double-blind, placebo-controlled SAD study. Healthy subjects in Part A received a single dose of Compound 2 or placebo in the fasted state. Subjects were clinically restricted from day -1 to day 6. Dosing in each cohort was staggered such that two subjects (one active: one placebo) were assessed for 48 hours post-dosing before the rest of the cohort was dosed. Each cohort received Compound 2 in ascending order. Dosing of sequential cohorts occurred based on a review of available safety data (up to Day 5) and plasma pharmacokinetic data (up to 24 hours) from the previous cohort. Dose escalation proceeded after a satisfactory review of these data. As pharmacokinetic and safety data from earlier cohorts became available, the doses evaluated in Cohorts 3a–4a were adjusted in increments of no more than 100 mg. The maximum total dose evaluated in Part A did not exceed 800 mg. The dosing regimen for Part A is shown in Table 32. zccAnn / zznz / E / YiAi TABLE 32 Dosage regimen for administration of compound 2, part A of study zccAnn / zznz / E / YiAi Cohort Population N (active: placebo) Compound 2 (Compound 1)* Healthy 6:2 50 (45) mg x 1 day 2a Healthy 6:2 100 (90) mg x 1 day 3a Healthy 6:2 200 (180) mg x 1 day 4a Healthy 6:2 400 (360) mg x 1 day *Clinical doses are expressed in terms of Compound 2, with the approximate equivalent base of Compound 1 in parentheses The healthy volunteers in Part A of the study were male and female subjects between the ages of 18 and 65. Active and placebo recipients were pooled within each Part A cohort to preserve blinding. Compound 2 was also tested in a single ascending dose (SAD) study to measure its safety, tolerability, pharmacokinetics, and antiviral activity in GT1-HCV-infected patients (Part B). Subjects in Part B received a single dose of Compound 2 in the fasted state. Patients were confined to the clinic from day -1 to day 6. Part B was initiated after review of the safety (up to Day 5) and plasma pharmacokinetic (up to 24 hours) data from Cohort 3a in Part A. The available safety (up to Day 5) and pharmacokinetic (up to 24 hours) data were reviewed for the first cohort in Part B (Cohort Ib) before enrolling subsequent Part B cohorts. Subsequent Part B cohorts were only dosed after review of the available safety and pharmacokinetic data for the respective doses in Part A, as well as the available safety (up to Day 5) data from the previous Part B cohorts. The dose escalation to 600 mg in HCV-infected patients was performed after a satisfactory review of these data. The dosing regimen for Part B is shown in Table 33. TABLE 33 Dosage regimen for Compound 2 in Part B of the study Cohort Population N (Active) Compound 2 (Compound 1)* Ib GT1 HCV-Infected 20.6 100 (90) mg x 1 day 2b GT1 HCV-Infected 20.6 300 (270) mg x 1 day 3b GT1 HCV-Infected 20.6 400 (360) mq x 1 day 4b GT1 HCV-Infected 20.6 600 (540) mq x 1 day zccRnn / zznz / E / YiAi *Clinical doses are expressed in terms of Compound 2, with the approximate basis of the equivalent Compound 1 in parentheses. Patients infected with HCV were non-cirrhotic GT1 surgery untreated subjects with a viral load of >5 logio lU / ml. No serious adverse events were reported, nor were any premature discontinuations required in Part A or Part B. All adverse effects were mild to moderate in intensity, and no dose-related patterns were observed, including laboratory parameters, vital signs, and ECGs. EXAMPLE 24 Results from the Single Dose Ascending (SAP) study of Compound 2 The pharmacokinetics of Compound 1 and the nucleoside metabolite 1-7 were measured after a single dose of Compound 2. The minimum C24 plasma concentrations (C24h) of metabolite 1-7 in HCV-infected patients after a 600 mg dose of Compound 2 were 25.8 ng / mL, which is more than twice the plasma concentration after a 300 mg dose of Compound 2. Metabolite 1-7 (shown in Chemical Equation 1) can only be generated through the dephosphorylation of the intracellular phosphate metabolite 1-4, metabolite 1-5, and metabolite 1-6, which is the active species. Therefore, metabolite 1-7 can be considered a substitute for the active species. Pharmacokinetic data for all cohorts are shown in Table 34 and Table 35. Values ​​are reported as mean ± standard deviation, except for Tmax where the median (range) is reported.Pharmacokinetic parameters were comparable in healthy patients and patients infected with HCV. TABLE 34 Human pharmacokinetics of Compound 1 v Metabolite 1-7 after administration of a single dose of Compound 2 in healthy volunteers Dose (mg) Cmax (ng / ml) Tmax (h) AUCtot (ng*h / ml) T1 / 2 (h) C24h (ng / ml) Part A, Healthy Subjects Comp 1 50 46.4 ±17.6 0.5 (0.5-0.5) 36.4 ± 12.3 0.32 ± 0.02 — 100 156 ± 96.3 0.5 (0.5-1.0) 167 ± 110 0.53 ± — 0.24 200 818 ± 443 0.5 (0.5-3.0) 656 ± 255 0.71 ± 0.16 — 400 1194 ± 401 0.5 (0.5-1.0) 1108 ± 326 0.86 ± 0.15 — Metabolite 1-7 50 27.9 ± 5.62 3.5 (3.0-4.0) 285 ± 69.4 7.07 ± 4.59 2.28 ± 0.95 100 56.6 ± 14.0 4.0 (3.0-6.0) 663 ± 242 17.7 ± 14.7 4.45 ± 1.87 200 111 ± 38.8 5.0 (3.0-6.0) 1524 ± 497 15.9 ± 7.95 13.7 ± 5.09 400 153 ± 49.4 6.0 (4.0-8.0) 2342 ± 598 15.6 ± 6.37 23.5 ± 6.31 zccRnn / zznz / E / viAi ♦Based on a 24-hour profile. TABLE 35 Human pharmacokinetics of Compound 1 v Metabolite 1-7 after administration of Compound 2 in GT1 HCV-infected patients Dose (mg) Cmax (ng / ml) Tmax (h) AUCtot (ng*h / ml) Tl / 2 (h) C24h (ng / ml) Comp 1 100 212 ± 32.0 0.5 (0.5-1.0) 179 ± 54.4 0.54 ± 0.12 — 300 871 ± 590 0.5 (0.5-1.0) 818 ± 475 0.64 ± 0.20 — 300 2277 ± 893 0.5 (0.5-1.0) 1856 ± 1025 0.84 ± 0.18 — 400 2675 ± 2114 1.0 (1.0-2.0) 2408 ± 1013 0.86 ± 0.18 — 600 3543 ± 1649 1.0 (0.5-1.0) 4132 ± 1127 0.70 ± 0.13 — Metabolite 1-7 100 50.2 ± 15.4 6.0 (4.0-6.0) 538 ± 103* 8.4 ± 4.3* 3.60 ± 0.40 300 96.9 ± 38.9 6.0 (3.0-6.0) 1131 ± 273* 8.1 ± 2.4* 10.9 ± 3.51 300 123 ± 16.6 4.0 (3.0-6.0) 1420 ± 221 __ 18.0 ± 8.83 400 160 ± 36.7 4.0 (4.0-4.0) 2132 ± 120 11.6 ± 1.21 22.5 ± 3.29 600 198 ± 19.3 4.0 (4.0-6.0) 2176 ± 116 — 25.8 ± 4.08 ♦Based on a 24-hour profile. The mean-time plasma concentration profiles of Compound 1 and metabolite 1-7 were also calculated for all cohorts in Part A and Part B of the study. Figure 21 shows the mean plasma concentration of Compound 1 after a single dose of the Compound 2, and Figure 22 shows the mean plasma concentration of metabolite 1-7 after a single dose of Compound 2. As shown in Figure 21, Compound 1 was rapidly absorbed and rapidly / extensively metabolized in all Part B cohorts. As shown in Figure 22, metabolite 1-7 was a major metabolite and exhibited sustained plasma concentrations. Plasma exposure to Compound 1 was dose-related, while exposure to metabolite 1-7 was dose-proportional. For subjects infected with Part B HCV, HCV RNA quantification measurements were performed before, during, and after administration of Compound 2. Plasma HCV RNA determinations were performed using a validated commercial assay. Baseline was defined as the mean of day -1 and day 1 (pre-dose). A single 300 mg dose of Compound 2 (equivalent to 270 mg of Compound 1) resulted in significant antiviral activity in subjects infected with GT1b-HCV. The mean maximum reduction in HCV RNA 24 hours post-dose after a single 300 mg dose was 1.7 log10 µU / mL, comparable to a reduction of -2 log10 µU / mL after 1 day of 400 mg sofosbuvir monotherapy in patients infected with human influenza virus in GT1a. The mean maximum reduction of HCV RNA 24 hours post-dose after a single 100 mg dose was 0.8 logio lU / ml.The mean maximum reduction in HCV RNA was 2.2 logio µU / mL after a single 400 mg dose. Individual pharmacokinetic / pharmacodynamic analyses for individual subjects in Part B of the study are shown in Figures 23A–23F. The concentration of metabolite 17-7 is plotted against the concentration reduction in HCV RNA, and as shown in Figures 23A–23F, the plasma reduction in HCV RNA correlates with plasma exposure to metabolite 1-7. The viral response is maintained with plasma concentrations of metabolite 1-7 that are greater than the EC95 value versus GTlb. The correlation between plasma concentration and HCV RNA reduction levels indicates that a deeper response can be achieved with higher doses of Compound 2. EXAMPLE 25 The predicted minimum steady-state levels of Metabolite 1-7 exceeded the EC95 values ​​of Compound 1 with respect to clinical isolates from HCV GT 1-4 As shown in Figure 24, the minimum steady-state plasma levels (C24,ss) of metabolite 1-7 after dosing Compound 2 in humans (600 mg QD (550 mg free base equivalent) and 450 mg QD (400 mg free base equivalent)) were predicted and compared to the EC95 of Compound 1 in vitro across all clinical isolates evaluated to determine if the steady-state plasma concentration is consistently higher than the EC95, which would result in high efficacy against any clinical isolates evaluated orally in vivo. The EC95 for Compound 1 is the same as the EC95 for Compound 2. For Compound 2 to be effective, the minimum steady-state plasma level of metabolite 1-7 must exceed the EC95. As shown in Figure 24, the EC95 of Compound 2 against all clinical isolates evaluated ranged from approximately 18 to 24 nM. As shown in Figure 24, Compound 2 at a dose of 450 mg, QD (400 mg free base equivalent) in humans, provides a predicted steady state through a minimum plasma concentration (C24,ss) of approximately 40 ng / ml. Compound 2 at a dose of 600 mg, QD (550 mg free base equivalent) in humans, provides a predicted steady state through a minimum plasma concentration (C24,ss) of approximately 50 ng / ml. Therefore, the predicted steady-state plasma concentration of the surrogate metabolite 1-7 is almost double the EC95 against all clinically evaluated isolates (even the hard-to-treat GT3a), indicating superior performance. In contrast, the EC95 of the sofosbuvir nucleotide standard of care ranged from 50 to 265 nM among all clinical HCV isolates evaluated, with an EC95 lower than the predicted steady-state concentration at the 400 mg commercial dosage for only two isolates, GT2 and GT2b. The EC95 for the 400 mg commercial dosage of sofosbuvir was higher than the predicted steady-state concentration for other clinical isolates: GTla, GTlb, GT3a, GT4a, and GT4d. The minimum steady-state plasma concentration (C24,ss) of 450 mg of Compound 2 was predicted using the minimum steady-state plasma concentration (C24,ss) of 300 mg. The mean minimum steady-state plasma concentration (C24,ss) at 300 mg was 26.4 ng / mL, and therefore the calculation was 26.4 * 450 / 300 = 39.6 ng / mL The minimum steady-state plasma concentration (C24,ss) of 600 mg was predicted using three approaches: 1) the mean C24 on Day 1 of 600 mg was 25.8 ng / ml and a 60% increase to reach steady state was assumed. Therefore, the calculation was 25.8*1.6=41.3 ng / ml; 2) the mean C24 on Day 1 of 400 mg was 22.5 ng / ml and a 60% increase to reach steady state was assumed. Taking into account dose-proportional PK, the calculation was 22.5*1.6*600 / 400=54 ng / ml; and 3) the minimum steady-state plasma concentration (C24,ss) of 300 mg was 26.4 ng / ml and dose-proportional PK was assumed. Therefore, the calculation was 26.4*2=52.8 ng / ml. The minimum steady-state plasma concentration (C24,ss) at 600 mg is the average of the 3 data points ((41.3+54+52.8) / 3=49.3 ng / ml). Overall, there is an approximately 60% increase in C24 at steady state compared to C24 after a single dose. The data comparing efficacy with steady-state pharmacokinetic parameters in Figure 24 clearly demonstrate the unexpected therapeutic importance of zccAnn / zznz / E / YiAi Compound 2 for the treatment of hepatitis C. In fact, the predicted steady-state plasma level (Cz4,ss) after administration of Compound 2 is predicted to be at least 2 times higher than the EC95 for all genotypes tested, and is 3 to 5 times more potent against GT2. These data indicate that Compound 2 has potent pan-genotypic antiviral activity in humans. As shown in Figure 24, the EC95 of sofosbuvir in GT1, GT3, and GT4 is greater than 100 ng / ml. Thus, surprisingly, Compound 2 is active against HCV in a dosage form that delivers a minimum steady-state concentration (40–50 ng / ml) that is lower than the minimum steady-state concentration (approximately 100 ng / ml) achieved by a similar dosage form of sofosbuvir. EXAMPLE 26 Description of the formulation and manufacture of Compound 2 A representative, non-limiting batch formulation for Compound 2 tablets (50 mg and 100 mg) is presented in Table 36. The tablets were produced from a common blend using a direct compression procedure as shown in Figure 25. The active pharmaceutical ingredient (API) was adjusted based on the as-is assay, with the adjustment being made to the percentage of microcrystalline cellulose. The API and excipients (microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium) were selected, placed in a V-blender (PK Blendmaster, 0.5 L bowl), and blended for 5 minutes at 25 rpm. Magnesium stearate was then selected, added, and the mixture was blended for an additional 2 minutes. The common blend was divided for use in the production of 50 mg and 100 mg tablets.The lubricated mixture was then compressed at a rate of 10 tablets / minute using a single-punch research tablet press (Korsch XP1) and a gravity powder feeder. The 50 mg tablets were produced using 6 mm round concave tools and forces of 3.5 kN. The 100 mg tablets were produced using standard 8 mm round concave tools and forces of 3.9–4.2 kN. zccAnn / zznz / E / YiAi TABLE 36 Formulation of 50 mg and 100 mg tablets of Compound 2 Raw Material % w / w / batch Mg / unit 50 mg Tablet 100 mg Tablet Compound 2 50.0 180.0 50.0 100.0 Microcrystalline Cellulose, USP / NF, EP 20.0 72.0 20.0 40.0 Lactose Monohydrate, USP / NF, BP, EP, JP 24.0 86.4 24.0 48.0 Croscarmellose sodium, USP / NF, EP 5.0 18.0 5.0 10.0 Magnesium stearate, USP / NF, BP, EP JP 1.0 3.6 1.0 2.0 Total 100.0 200.0 zccAnn / zznz / E / YiAi Compound 2 was adjusted based on the as-is assay, with the adjustment being made to the percentage of microcrystalline cellulose. Compound 2 and the excipients (microcrystalline cellulose, lactose monohydrate, and croscarmellose sodium) were selected, placed in a V-blender (PK Blendmaster, 0.5 L bowl), and blended for 5 minutes at 25 rpm. Magnesium stearate was then selected, added, and the mixture was blended for an additional 2 minutes. The resulting mixture was divided for use in the production of 50 mg and 100 mg tablets. The lubricated mixture was then compressed at a rate of 10 tablets / minute using a single-punch research tablet press (Korsch XP1) and a gravity powder feeder. The 50 mg tablets were produced using 6 mm round concave tooling and forces of 3.5 kN. The 100 mg tablets were produced using standard 8 mm round concave tools and forces of 3.9-4.2 kN.The specifications for the 50 mg and 100 mg tablets are shown in Table 37. TABLE 37 Specifications for 50 mg and 100 mg tablets of Compound 2 50 mg Tablets 100 mg Tablets Average weight (n=10) 100 + 5 mg 200 + 10 mg Individual weight 100 + 10 mg 200 + 20 mg Hardness 5.3 kp 8.3 kp Disintegration < 15 minutes < 15 minutes Friability NMT 0.5% NMT 0.5% The 50 mg and 100 mg tablets produced as described above were subjected to 6-month stability studies under three conditions: 5°C (refrigerated), 25°C / 60% RH (ambient), and 40°C / 75% RH (accelerated). Both the 50 mg and 100 mg tablets were chemically stable under all three conditions tested. Under refrigerated conditions (5°C), both the 50 mg and 100 mg tablets remained solid white with no change in appearance from T = 0 to T = 6 months. Throughout the 6-month study, impurities greater than 0.05% were reported for either the 50 mg or 100 mg tablets. The water content after 6 months was also less than 3.0% w / w for both tablets. Similar results were reported when the tablets were subjected to room temperature conditions (25°C / 60% RH); impurities greater than 0.05% were reported throughout the 6 months for both tablets, and the water content did not exceed 3.0% w / w at the 6-month mark. When the tablets were subjected to accelerated conditions (40°C / 75% RH), the appearance of the 50 mg and 100 mg tablets remained unchanged from a round white tablet. An impurity was reported after 3 months, but the impurity was only 0.09%.A second impurity was reported after 6 months, but the total impurity percentage was only 0.21% for the 50 mg and 100 mg tablets. The water content was 3.4% w / w at 6 months for the 50 mg tablets and 3.2% w / w for the 100 mg tablets. In a separate study, the stability of Compound 2 50 mg and 100 mg tablets at room temperature (25°C / 60% RH) was measured over 9 months. The appearance of the 50 mg and 100 mg tablets remained unchanged from a round, white tablet over the course of 9 months. Impurities in the 50 mg tablet were less than 0.10% after 9 months, and impurities in the 100 mg tablet were less than 0.05%. The water content of the 50 mg and 100 mg tablets after 9 months was only 2.7% w / w and 2.6% w / w, respectively. This specification has been described with reference to embodiments of the invention. However, a person skilled in the art will appreciate that various modifications and changes can be made without departing from the scope of the invention as set forth in the following claims. Accordingly, this specification should be regarded in an illustrative and not restrictive sense, and all such modifications are intended to be included within the scope of the invention.

Claims

1. A compound with the formula:

2. The compound of claim 1, optionally in a pharmaceutical vehicle, for use in the treatment of a hepatitis C infection, or a condition resulting from a hepatitis C infection, in a host in need.

3. A pharmaceutical composition, characterized in that it comprises an effective therapeutic amount of a compound of formula in a pharmaceutically acceptable vehicle.

4. The pharmaceutical composition of claim 3, in a solid dosage form delivering from 1 milligram to 2,000 milligrams of the compound.

5. The pharmaceutical composition of claim 3, in a solid dosage form that releases from 100 to 800 milligrams of the compound.

6. The pharmaceutical composition of claim 3, in a solid dosage form delivering at least 500 mg of the compound.

7. The pharmaceutical composition of claim 3, in a solid dosage form delivering at least 600 mg of the compound.

8. The pharmaceutical composition of claim 3, in a solid dosage form delivering at least 700 mg of the compound.

9. The pharmaceutical composition of claim 3, wherein the pharmaceutically acceptable vehicle is suitable for oral administration.

10. The pharmaceutical composition of claim 9, wherein the pharmaceutically acceptable vehicle is in tablet form.

11. The pharmaceutical composition of claim 9, wherein the pharmaceutically acceptable vehicle is in capsule form.

12. The pharmaceutical composition of claim 3, in intravenous formulation.

13. The pharmaceutical composition of claim 3, in parenteral formulation.

14. The pharmaceutical composition of claim 13, wherein the pharmaceutically acceptable vehicle is in the form of a suspension or solution.

15. A compound of formula zccAnn / zznz / E / YiAi wherein the compound is at least 90% free of the opposite phosphorus S enantiomer.

16. The compound of claim 15, wherein the compound is at least 98% free of the opposite phosphorus S enantiomer.

17. A solid dosage form comprising an effective amount in a pharmaceutically acceptable vehicle of a compound of formula: wherein the compound is at least 90% free of the opposite phosphorus S-enantiomer.

18. The solid dosage form of claim 17, wherein the compound is at least 98% free of the opposite phosphorus S-enantiomer.

19. A pharmaceutical composition, characterized in that it comprises an effective therapeutic amount in a pharmaceutically acceptable vehicle of a compound of formula zccAnn / zznz / E / YiAi wherein the compound is at least 90% free of the opposite phosphorus S-enantiomer.

20. The pharmaceutical composition of claim 19, wherein the compound is at least 98% free of the opposite phosphorus S-enantiomer.

21. A compound with the formula:

22. A pharmaceutical composition, characterized in that it comprises an effective amount in a pharmaceutically acceptable vehicle of the compound of claim 21, in a pharmaceutically acceptable vehicle.

23. The pharmaceutical composition of claim 22, in oral dosage form.

24. The pharmaceutical composition of claim 23, wherein the oral dosage form is a solid dosage form.

25. The pharmaceutical composition of claim 24, wherein the solid dosage form is a tablet.

26. The pharmaceutical composition of claim 24, wherein the solid dosage form is a capsule.

27. The pharmaceutical composition of claim 23, wherein the oral dosage form is a liquid dosage form.

28. The pharmaceutical composition of claim 27, wherein the liquid dosage form is a suspension or solution.

29. The pharmaceutical composition of claim 22, in intravenous formulation.

30. The pharmaceutical composition of claim 22, in parenteral formulation.

31. A compound with the formula:

32. The compound of claim 31, of formula: 10 33. The compound of claim 31, of formula:

34. A pharmaceutical composition, characterized in that it comprises any of the 15 claims 31-33, in a pharmaceutically acceptable vehicle.

35. Use of a compound of formula zccAnn / zznz / E / YiAi, optionally in a pharmaceutically acceptable vehicle, in the preparation of a medicament for the treatment of hepatitis C infection or a condition resulting from hepatitis C infection, in a host in need. 5 36. The use of claim 34, wherein the compound is adapted to be administered orally.

37. The use of claim 34, wherein approximately 100 to approximately 800 mg of the compound can be administered.